Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
1
Sodium Borohydride Digest Copyright: October 2003 Rohm and Haas… Quality, Service and Innovation in Borohydride Products Rohm and Haas (formerly Metal Hydrides Inc.) broke ground on the world’s first large-scale sodium borohydride plant in 1956, making possible the widespread use of this important chemical. Four and a half decades later, we have two world-class plants (USA and NL), a wide variety of product forms (Powder, Granular, Caplets, Aqueous Solutions and Organic Solutions) and a worldwide comprehensive customer support. While we are proud of our role as innovator in the sodium borohydride market, we understand that continued success depends on giving our customers the tools they need to move from concept to finished product. The Sodium Borohydride Digest is an important part of our efforts to help users understand the wide utility of sodium borohydride reductions in organic Organic Synthesis. For example, sodium borohydride has long been the reagent of choice for reducing aldehydes and ketones to alcohols. It has also become well known for situations where selective reductions are needed. However, many organic chemist may be less familiar with the facts that successful reduction are also possible with acid chlorides, imines, esters, carboxylic acids, unsaturated cyclic quaternary compounds and many other functional groups. The Digest is designed to allow readers to survey the entire spectrum of sodium borohydride chemistry and to obtain more details on reactions of interest. Illustrations of reductive chemistry are followed wherever possible, by the corresponding Chemical Abstracts references, which are collected at the end of each section. In addition when ever possible reference to Alembic will be sited. The Alembic is a publication that intends to highlight one specific chemical topic with possible interest for Organic Synthesis on industrial scale.
*For Online Consulting Only
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
2
In addition, the Sodium Borohydride Digest is a guide to sodium borohydride’s relative position among reducing reagents. We include table showing common functional groups and their general reducibility by sodium borohydride, sodium borohydride derivatives and by some analogous aluminohydride reducing agents. Within the market of chemical reducing agents in organic synthesis, NaBH4 is the primary reductant used on industrial scale, with a estimated (equivalent) market share greater than 50%. Some of the benefits of using borohydride chemistry include : - the least expensive metal hydride commercially available (on a hydride equivalent basis) - safe with regards to storage and use & handling - industrial implementation requires no or limited equipment investment - ease of work-up (water soluble boron salts) - ubiquitous solvents such as water and methanol are typically employed - unique and versatile as a hydride reducing agent for both chemo- and diastereo-selectivity Rohm and Haas welcomes request for additional information and will gladly provide technical assistance to those interested in developing or optimizing sodium borohydride applications. Our research and technical service groups can provide assistance by telephone or, if appropriate, by visiting your facility. We can furnish technical literature on a wide variety of applications. Finally, Rohm and Haas, as a subscriber to the Responsible Care® Codes, is committed to the safe use of our products. We have wide variety of information and presentations on safety and handling.
John Yamamoto, Ph.D Editor Rohm and Haas Company Synthesis & ProcessApplications
*For Online Consulting Only
Rohm and Haas : the Sodium Borohydride Digest
Please feel free to send us your questions via
[email protected], or contact one of our offices in America: Rohm and Haas Company Borohydride Applications 60 Willow Street Phone: 1-978-557-1832 Fax: 1-978-557-1879
in Asia: Rohm and Haas China, Inc. 23rd Floor, Hitech Plaza No. 488 S. Wu Ning Road Shanghai, China Phone: +86 21 6230 6366 Fax: +86 21 6230 6377
Updated information can be found at : http://www.hydridesolutions.com/
*For Online Consulting Only
3
press -F for Searching
in Europe: Rohm and Haas France S.A. la tour de Lyon 185, rue de Bercy F-75579 Paris Phone: +33-1 4002 5210 Fax : +33-1 4002 5441
:
4
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest
TABLE OF CONTENTS I. Properties A. Physical and Thermodynamic B. Solubility C. Stability II. Organic Reductions A. Theory B. Practice C. Carbonyl groups Aldehydes Ketones Acids Amides Anhydrides Acid Halides Esters Enol Esters Imides Lactone D. Carbon-Nitrogen Compounds Reductive Amination Azides Deamination Diazonium Salts
*For Online Consulting Only
Page # 6 7 9 14 16 28 28 35 51 55 57 59 63 71 72 74 77 82 85 86
Heterocyclic C=N Bonds Hydrazones Imines Nitriles Nitro Nitroso Oximes Quaternary Compounds E. Miscellaneous Organic Reductions Carbonium Ions Reductive Cleavage Reductive Cyclization Dehalogenantions Demercurations Double bonds Epoxides Organo Calcogen Compounds Ozonides Peroxides and Hydroperoxide III. Inorganic Applications A. Inorganic Reductions Metal Cation Reduction Metal Anion Reduction B. Organometallic C. NaBH4 Derivatives
87 92 97 98 101 105 107 110 114 116 119 122 125 128 133 135 140 141 143 143 145 155 160
Rohm and Haas : the Sodium Borohydride Digest
Sodium Cyanoborohydride 160 Polymer Bound borohydrides 161 Other Solid Supports 162 NaBH2S3 Lanacett’s Reagent 162 NaBH(OR)3 Sodium Hydridotrialkoxyborates 163 NaBH4 Polyamine Polymer 163 Lithium Borohydride 164 Potassium Borohydride 164 Calcium Borohydride 164 Zinc Borohydride 164 Mixed Hydrides 165 Esters and Acids 165 Acetals and Ketals 165 166 Hydroboration with NaBH4 Other Derivatives 167 IV/ Analytical Procedures A. Assay Methods 179 Trace Methods for Borohydrides 180 NaBH4 AssayHydrogen Evolution Method 182 Iodate Method 185 Trace NaBH4 AssayHydrogen evolution 188 Iodate Method 191 NBC Method 193
*For Online Consulting Only
5
press -F for Searching
Crystal Violet Method
195
V. Availability VI. Personal Protective Equipment VII. First Aid VIII. Reactivity IX. Fire Fighting/ Flammability X. Spill And Waste Disposal XI. Toxicity XII. Storage And Handling XIII. Shipping
198 199 200 202 204 205 207 208 210
Rohm and Haas : the Sodium Borohydride Digest
I. PROPERTIES A. Physical and Thermodynamic Properties These properties are listed in the following two tables. Infrared and Raman spectra of both sodium and potassium borohydrides have been reported (1). Table I Selected Physical Properties of Sodium Borohydride Properties Formula NaBH4 Molecular Weight 37.84 Purity >98.5% Color White Crystalline Form Face Centered cubic (anhydrous) a= 6.15 Å (dihydrate)Exists below 36.5 oC Melting Point 505 oC (10 atms H2) Decomposes above 400 oC In Vacuum Thermal Stability Will not ignite above 400 oC on a hot plate Ignites from free flame in air, Burning quietly Density 1.074g/cm3 Apparent Bulk Density 5lb/gal *For Online Consulting Only
6
press -F for Searching
Table II Thermodynamic Properties of Sodium Borohydride Function Value Ref Free Energies of Formation Heat of Formation Entropy Heat Capacity Free Energy of Ionization NaBH4(s)= Na+ + BH4-
Borohydride ion BH4- (aq.) Free Energy of Formation Heat of Formation Entropy Hydrolysis BH4- + H+ + 3 H2O (liq)= H3BO3 + 4 H2(g) Oxidation BH4- + 8 OH- = B(OH)4- + 4 H2O + 8e-
∆Fo298 ∆Ho298 So Co p ∆Fo298
-30.1 kcal/mol -45.53 kcal/mol +24.26 cal/omol +20.67 cal/omol -5660 cal/mol
3 2 5 3 4
∆Fo298 ∆Ho298 So298
+28.6 kcal/mol +12.4 kcal/mol +25.5 cal/omol
4 4 4
∆Fo298 ∆Fo298 Eo298
-88.8 kcal/mol -228.9 kcal/mol +1.24 V
4 4 4
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest
gm. NaBH4 in 100g saturated solution
B. Solubility 1. Water The solubility of sodium borohydride in water, the most commonly used solvent, has been accurately measured at the different temperatures by Jensen (6). The data presented in the following graph shows the equilibrium temperature of the two crystal forms NaBH4 and NaBH4•2 H2O. The curve below 36.4oC represents the solubility of the dihydrate, and above 36.4oC, the solubility of anhydrous NaBH4. 55 50 45 40 35 30 25 0
20
40
60
Temperature o C
Figure 1. The solubility of sodium borohydride in water at different temperatures.
*For Online Consulting Only
7
2. Nonaqueous Solvents The solubility of sodium borohydride in different solvents has been determined accurately at different temperatures for many alcohols, amines, and glycol ethers. In general, sodium borohydride is soluble in polar compounds containing a hydroxyl or amine group. A point to note is the glycol ethers differ from most solvent in that their ability to solubilize sodium borohydride decreases as solvent temperature increases. See table III.
Rohm and Haas : the Sodium Borohydride Digest
Table III NaBH4 Solubility in Various Solvents (g/100g of solvent)
Solvent Water Liquid Ammonia Methylamine Ethylamine N-Propylamine Iso-Propylamine N-Butylamine Cyclohexylamine Morpholine Aniline Pyridine Monoethanolamine Ethylenediamine Methanol Ethanol
Temp(oC) 0 25 60 25 -22.0 17 28 28 28 28 25 75 75 25 75 25 75 20 20
Solubility 25.0 55.0 88.5 104.0 27.6 20.9 9.6 6 4.9 1.8 1.4 2.5 0.6 3.1 3.4 7.7 22.0 16.4 (reacts) 4.0 (reacts slowly)
Iso- Propanol Tert-Butanol
25 60 25
*For Online Consulting Only
0.37 0.88 0.11
8
press -F for Searching
2-Ethylhexanol Tetrahydrofurfuryl Alcohol Ethylene glycol dimethyl ether Diethylene glycol dimethyl ether
Triethylene glycol dimethyl ether
Tetraethylene glycol dimethyl ether
Dimethylformamide Dimethylacetamide Dimethylsulfoxide Acetonitrile Tetrahydrofuran
60 25 20 0 20 0 25 45 75 0 25 50 100 0 25 50 75 100 20 20 25 28 20
01.8 0.01 14.0 (reacts slowly 2.6 0.8 1.7 5.5 8.0 0.0 8.4 8.7 8.5 6.7 8.7 9.1 8.4 8.5 4.2 18.0 14.0 5.8 2.0 0.1
Rohm and Haas : the Sodium Borohydride Digest
3. Non-Solvents In cases where sodium borohydride is not soluble, traces amounts of water or low molecular weight alcohols can be added to the organic solvent to effect reduction. In general, two moles of water are needed for every mole of sodium borohydride. This procedure has proven effective with very high molecular weight alcohols. In some cases, however, an organic borohydride such as tetraethylammonium borohydride will be more effective because of its greater solubility. The use of NaBH4 on solid supports such as silica gel, alumina, and zeolites in nonpolar solvents has been published (See section IIIC). C. Stability Sodium borohydride is very stable thermally. It decomposes slowly at temperatures above 400oC in vacuum or under a hydrogen atmosphere. Sodium borohydride absorbs water rapidly from moist air to form the dihydrate complex, which decomposes slowly forming hydrogen and sodium metaborate. Decomposition in air is therefore a function of both temperature and humidity. Generally higher reaction temperatures favor borohydride reductive chemistries.
*For Online Consulting Only
press -F for Searching
9
1. Aqueous Solutions The stability of sodium borohydride in water is dependent upon the temperature and the pH. Increasing the temperature and lowering the pH accelerates the hydrolysis reaction. NaBH4 + 4 H2O Æ NaB(OH)4 + 4 H2 As the borohydrides are alkaline, the higher the concentration, the more stable the resulting solutions. See Table IV. Table IV pH of Solutions of NaBH4 at 24oC Concentration of pH NaBH4 1.000M 10.48 ± 0.02 0.100M 10.05 ± 0.02 0.010M 9.56 ± 0.02 The kinetics of the hydrolysis reaction has been studied by Gardiner and Collat (7,8), Wang and Jolly (9), and by Kreevoy (10,12). The reaction is pseudo-first order and is subject to general acid catalysis. First order kinetics also applies in strongly alkaline solution (13). The decomposition rate of aqueous NaBH4 solutions can be estimated conveniently (14) using equation Log10t1/2(mins)= pH-(0.034T-1.92)
where t1/2 is the half-life in minutes and T is the temperature (kelvin scale). Table V. numerically shows the relationship between pH and the half-life of NaBH4 at 25 oC in an aqueous solution. Table V: pH Vs Half life of SBH pH NaBH4 Half life 4.0 0.0037 sec. 5.0 0.037 sec 5.5 0.12 sec 6.0 0.37 sec 7.0 3.7 sec. 8.0 36.8 sec. 9.0 6.1 mins 10.0 61.4 mins 11.0 10.2 hours 12.0 4.3 days 13.0 42.6 days 14.0 426.2 days The hydrolysis of sodium borohydride in water causes a rise in pH value, and the rate of decomposition therefore decreases. For example, a 0.01 M solution of NaBH4 has an initial pH of 9. 6 that changes during hydrolysis to 9.9.
*For Online Consulting Only
10
press -F for Searching
(a) Effect of pH It is obvious, therefore, that the addition of sodium hydroxide will stabilize aqueous sodium borohydride solutions. This was demonstrated by Jensen (6) over a pH range of 12.9 to 13.8 (calc.) At higher pH values there is essentially no decomposition during storage. 100 98 % NaBH4
Rohm and Haas : the Sodium Borohydride Digest
96
0.10 N NaOH 0.25 N NaOH 1.00N NaOH
94 92 90 88 86 0
50
100
150
Time (hours)
Figure 2. Effect of pH on stability of NaBH4 solutions. (b) Effect of Temperature If the temperature is increased, the stability decreases as shown in Fig.1. This can be compensated for, by adding more caustic or increasing the sodium borohydride concentration.
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest
11
a rate of only 5x10-6% per day at 21oC and at 4x10-5% per day at 54oC. 100 % NaBH4
90 80
24.0 oC 47.0o C
70 60 50 40 0
50
100
3. Tetraglyme solutions (Venpure OGS) Venpure OGS is a tetraglyme solution of 8.5 % sodium borohydride. This solution is to be used when sodium borohydride is needed in an aprotic solvent. The stability of the sodium borohydride in this solvent is very good, no decomposition of the NaBH4 occurs after 336 hour at either 24 or 60 oC.
Time (hour)
Figure 3. Stability of an alkaline solution (1.00 N NaOH) of sodium borohydride (0.10 M NaBH4) at 24o C and 46o C (c) Effect of catalysts Noble metals, copper, nickel and cobalt borides (15-23) catalyze the hydrolysis of the borohydride ion; the catalyst is frequently formed by borohydride reduction of the corresponding metal salts in solution. 2. Aqueous solutions (VenPure) VenPure Solution is a stabilized water solution of sodium borohydride in caustic soda. Such a solution containing 12% NaBH4 and 40% NaOH, decomposes at
*For Online Consulting Only
4. Alcohol Solutions. NaBH4 is unstable in acidic alcohols (e.g. phenol) and low molecular weight primary alcohols such as methanol, ethanol and ethylene glycol due to solvolysis but is stable in secondary and tertiary alcohols such as isopropanol, t-butanol and 2ethylhexanol, even at elevated temperatures (24,25). It reacts with higher molecular weight primary alcohols. The instability in lower alcohols can be overcome by the addition of base, as in aqueous solutions. For example, Jensen (6) has reported that ethanol only 5.7% of the sodium borohydride is lost in 144 hours at 24oC in the presence of 2 N sodium hydroxide. Studies undertake at Rohm and Haas have demonstrated that the addition of as little as 0.01 N MeONa to a methanol solution or 0.01N NaOEt to an Ethanol solution of
Rohm and Haas : the Sodium Borohydride Digest
sodium borohydride can substantially suppress the hydrolysis of NaBH4 as shown in the graphs below.
80 No NaOMe added 0.010 N NaOMe
60 40 20
30 % NaBH4 Consumed
% NaBH4 consumed
100
25 20
0.001 NaOEt
15
0.1 NaOEt
10
No NaOEt
5 0 0
0 0
10
20
30
2 Time, Hours
40
Time (minutes)
Figure 4. Effect of the addition of NaOMe on solvolysis of NaBH4 in methanol over a short period of time.
12
press -F for Searching
Figure 5. Effect of the addition of NaOEt on the solvolysis of sodium borohydride in ethanol at 30 oC. 100 80 0.1N NaOMe 30 oC
60 40
0.1N at 50 oC
20 0 0
200 Ti m e ( M i nu t e s)
Figure 6. Effect of Temperature on the solvolysis of NaBH4 in methanol with NaOMe. *For Online Consulting Only
Rohm and Haas : the Sodium Borohydride Digest
3 2,5 2 1,5 1 0,5 0
0.01NaOEt at 50°C 0.01NaOEt at 30°C
0
0,5
1
Ti m e ( ho ur s)
Figure 7. Effect of Temperature on the solvolysis of SBH in ethanol with NaOEt. 5. Other Solvents The stability of sodium borohydride solutions in organic solvents is dependent upon the amount of hydrolysis that can occur. In solvents such as Glymes, DMAC, NMP, pyridine and dioxane, where there is no chance of hydrolysis, sodium borohydride is stable indefinitely. As soon as water is present in significant amounts, hydrolysis can occur and affect the stability. While dilute solutions of NaBH4 in dimethlyformamide (DMF) have been used many times without incident, a violent exothermic reaction was reported (26) involving
*For Online Consulting Only
press -F for Searching
13
a saturated (4.7M) solution and resulting in spontaneous ignition of the flammable gases evolved. Laboratory investigation at Rohm and Haas showed that after a temperature-dependent induction period, a runaway reaction occurs in concentrated (>2M) NaBH4-DMF solutions in which DMF is reduced to trimethyl amine. The reaction is accelerated by small amounts of carboxylic acids. Formic acid is known to be present in commercial DMF in ppm quantities as a result of slight hydrolysis. Dimethylacetamide (DMAC), which is also a good solvent for NaBH4, does not react violently with NaBH4 under similar conditions. In view of the above findings, we strongly advise caution in working with NaBH4 in DMF. We recommend substitution of dimethylacetamide as safer solvent especially if the use of concentrated solutions or elevated temperatures is contemplated.
D
O D
R
δ-
O R
W
W δ+
Least reactive Most reactive Because of this, any substituent that increases the fractional positive charge on the carbonyl carbon atom will increase the rate of reduction. If the fractional positive charge is decreased by substituents, then the rate is slowed. Jensen (6), for example, has shown that the rate of reduction for substituted benzaldehyde derivatives is as shown in Figure 8. In this case, the inductive effect leading to a greater positive charge is overcome by the resonance effect.
100 90 80 70 % Reduction
II. ORGANIC REDUCTIONS A. Theory The rate of addition of sodium borohydride to a ketoneic carbon is directly related to the magnitude of the charge on that carbon. O
14
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest
Benzaldehyde
60
Salicyladehyde
50
m-hydroxybenzaldehyde
40
p-hydroxybenzaldehyde b-Resorcylaldehyde
30 20 10 0 0
50
100
Time (minutes)
Figure 8. Rate of reduction of benzaldehyde and a few hydroxybenzaldehydes. With perfluoro compounds, however, the inductive effect is clearly shown, and it has been demonstrated (27) that fluorinated esters are reducible by NaBH4 in nonaqueous systems in good yield. R-CF2-COOEt Æ R-CF2CH2-OH The presence of metal ions, either as a catalyst (28, 29), or to form other more powerful or stereo selective borohydrides, and solvents (24) can influence reductions with NaBH4.
*For Online Consulting Only
Rohm and Haas : the Sodium Borohydride Digest
The mechanism of borohydride reductions of aldehydes or ketones in the presence of alcohols was initially thought to proceed by a stepwise hydride ion transfer to the carbonyl carbon, resulting in formation of a tetraalkoxyborate containing the substrate being reduced. Subsequent hydrolysis of the complex, during work up, generated the product alcohol.
The first model to predict the stereoselectivity of hydride reductions of carbonyl groups was proposed by cram in 1952 (35-36). This model proposed that the hydride atom attacks the carbonyl group form the direction of the smallest substituent as shown in figure 10. O R
R
R
In any case, kinetic studies show that the first step in the process must be rate controlling.
*For Online Consulting Only
NaBH4 +
OH O
+
Various aspects of the relatively few mechanistic studies reported in ensuing years served only to cloud the issue. These included solvent and cation effects (24,25), Kinetic observations (30) that suggested complete disproportionation of alkoxyborohydride intermediates to regenerate BH4- as the actual reducing agent, and questions on the origin of stereoselectivity. Detailed studies by Wigfield (31-34) indicate that during carbonyl reductions in alcohol solvents, the alkoxyborate anion intermediate contains the solvent alkoxy rather than that of the product. (Figure 9) Isotope studies show that disproportionation of the intermediate back to BH4- does not occur.
15
press -F for Searching
R
H
K1
O H H
B
R' H H
R'OH
Figure 9
H R
R
K2
+ NaBH3OR'
H103o H
O R M
HO
S
P,L H
O
H-
R M
S
M
P,L
cation adds steric bulk to the molecule, which will increase the specificity of the attack of the hydride. HR
S
P,L R
R
M
16
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest
O
S M
L
S Metal
R
M
H OH L
OH S
P,L
Figure 10 In 1968 Felkin improved on Cram's model by proposing that the bulkiest substituent could also be the most electron-withdrawing group regardless of steric size. (37) These new conclusions were later substantiated by the theoretical calculations of Ahn. (3840) The theoretical calculations also showed that the hydride attacking the carbonyl group approaches at a 103o angle instead of 90o. Another model set forth by Cram in 1952 proposed that substrates containing a chelating group in the α or β position will chelate with a metal cation to form a five or six membered ring. (41) The chelating
*For Online Consulting Only
See the section on ketones for further details. B. Practice Sodium borohydride is an attractive reducing agent for organic substrates because of its convenience as well as its selectivity and efficiency. The general techniques of its use are by now well known to the practitioners of organic synthesis, who also knows that modifications are sometimes dictated by the properties (solubility, thermal stability, pH sensitivity) of the materials being reduced. Nevertheless, a few comments are in order, to ensure the reagent’s effective use. Part of the convenience associated with sodium borohydride reductions lies in the fact that, unlike most other complex hydrides, it is not necessary to exclude moisture and atmospheric oxygen from the reaction mixture. While some of
Rohm and Haas : the Sodium Borohydride Digest
the borohydride will be consumed by reaction with any water present, this will not have any adverse effect on the desired reduction, provided that sufficient borohydride is present. This is the main reason why hydride reductions customarily use a slight excess of reducing agent. The selection of a solvent for a NaBH4 reduction can influence the results. Water and lower alcohols are most commonly used, but the solubility characteristics of the material being reduced may dictate selection of a different solvent (see Table III for NaBH4 solubility information.) It is important to note that while the literature containing numerous references to borohydride reductions in methanol, NaBH4 is not stable in this solvent, especially at elevated temperatures. Interaction of NaBH4 and methanol, analogous to hydrolysis, takes place readily unless the reducing agent solution is stabilized by the addition of alkali. Ethanol and isopropanol, in which NaBH4 is less soluble, are preferable because of their much slower rates of solvolytic reaction with NaBH4. Water is a good solvent for NaBH4 and is recommended for watersoluble compounds. As is true with methanol, however, addition of alkali to stabilize the borohydride solution may be warranted.
*For Online Consulting Only
press -F for Searching
17
In simple ketone reductions, as well as in many other cases, the order of addition has no effect on the course of the reaction and the yields obtained. The conversion in complex hydride reductions is analogous to that of Grignard reactions in that addition of substrate to the reducing solution is considered the normal method. This order of addition is used even with alkali-sensitive compounds, such as aldehydes or aminoketones, since only a small amount of starting material at a time is subjected to the alkaline conditions of the reducing agent and this is rapidly reduced. After completing the reduction reaction, destruction of any unreacted borohydride is recommended before attempting product isolation or workup. This can be accomplished by addition of excess acetone that rapidly consumes borohydride. Alternatively, dilute aqueous base or dilute mineral acids can be added for the same purpose. Note that concentrated acids must never be used because of the potential for formation of hazardous boranes, which may also cause undesired reduction of other functional groups present. Provision should be made to vent safely any hydrogen gas formed during destruction of unreacted borohydride. See section VI for additional details. 1) Phase Transfer Catalysis This general discussion of the practical aspects of applying sodium borohydride as a reducing agent would not be complete without mentioning the increasing use of phase
Rohm and Haas : the Sodium Borohydride Digest
transfer catalysis (PTC) as a means of overcoming solvent incompatibilities between the borohydride and the substrate to be reduces (42-45). Quaternary ammonium salts, such as tetrbutylammonium ion, are the most commonly used catalysts. In fact, preformed tetrabutyl ammonium borohydride has also been used for reductions in aprotic solvents such as ethylene chloride (38). Crepitates (39) and chiral functional polymers (40-43) have also been applied in PTC reductions with sodium borohydride. Continuing interest in stereospecific reductions has resulted in the use of chiral quaternary ammonium salts as phase transfer catalysts. Asymmetric induction has been demonstrated to occur when ephedrinium salts are used in PTC reductions with sodium borohydride (44-46). 2) Chemically Modified Borohydride Anion Modifying the chemo and/or enantio-selective reductive properties of NaBH4 with the addition of either an organic or inorganic modifier has opened areas of reductive chemistry that were normally considered inaccessible to NaBH4. Two classes of reagent that have been used to modify sodium borohydride are carboxylic acids (55-56), chiral alcohols (57), sugars (58-62), tartaric acid (63) and lactic acid (64-65).
*For Online Consulting Only
press -F for Searching
18
The reaction of carboxylic acids with NaBH4 forms either mono or tris-substituted acyloxyborohydrides, which have unique reactive properties depending on the quantity of acid, added to the reaction. The true strength of this system is realized with the reduction of nitrogen containing organic molecules such as immines, oximes, enamines, iminium salts and heterocyclic compounds. Reductive aminations can be done efficiently using this system. Two reviews exploring the vast chemistry of this methodology has been published recently (55-56). Finally, chiral alcohols have been added to the NaBH4 reducing system to induce selective enantiomeric reduction of organic functional groups. This selectivity is induced by asymmetric induction. Chiral alcohols such as amino alcohols, sugars and tartaric acid have been used to accomplish these selective reductions (55-65). 3) Changing of the Cation Many different metal salts have been used with sodium borohydride to form new more powerful and selective reducing reagents. The most common metals to be added are LiCl (66), ZnCl2 (67-79), TiCl4(80-82), Ti(Isopropoxide)4 (8385), Cp2TiCl2 (87), CeCl3 (88-89), CaCl2 (90-92) and lanthanide salts (93). The use of these metal salts to modify the chemo, stereoslectivity and the reductive strength of the NaBH4 towards organic functional groups have been and are
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest
currently being studied. A review has recently been written on this subject. 4) Modification of the substrate. Recently cynuric acid (94) and BOP (95) have been added to solutions of carboxylic acids prior to treatment with sodium borohydride, to help the reduction of carboxylic acid groups under mild conditions. This methodology makes it possible to convert amino acid to amino achohols under very mild conditions. Cl
Cl O R
+ OH
Cl
N
NMM, DME
N N
Cl
3h, RT
O R
N
NaBH4, H2O
N N
Cl
0 oC
R
OH
Cyclodextrin have recently been used as an additive to help induce stereoselectrive reduction of carbonyl groups. This reagent works by forming an inclusion complex with the substrate to be reduced in such a way as to allow the addition of hydride to the functional group from one direction only (96-101).
19
5) Co-catalyst: The use of catalysts to increase the chemo and stereo selectivity of sodium borohydride has been demonstrated recently. Adiminato Co(II) complexes have reduced ketones as well as carboxyamides and imines functional groups stereoselectively (102-106). Other inorganic and organic catalysts have been reported (107). 6) Supported borohydrides The impregnation of organic and inorganic polymers such as ion exchange resins, zeolites, silica gel, alumina or aluminophosphates with sodium borohydride or derivative has been used to stereoselectively and chemoselectively reduce organic functional groups. Depending on the nature of the support, the type of borohydride reagent used and the type of co-reagent are used, different chemo and stereoselectivities can be achieved. These reductive systems have advantages such as with the exchange resins, the spent borohydride are easily separated from the product by filtration and with silica gel and alumina reactions can be done in aprotic solvents such as hexane. 7) In situ or ex situ production of diborane. Diborane, B2H6 can be synthesized directly from borohydride in high yields using many different reagents. Reagents that can accomplish this transform are H2SO4 (108-
*For Online Consulting Only
Rohm and Haas : the Sodium Borohydride Digest
111), I2 (112-120), Me3SiCl (121-122), TiCl4 (123-124), BF3 (125-128) and others. These reaction can be done either in situ where the compound to be reduced and the reagents to generate diborane are placed in to the same reaction flask or the diborane which is a gas at room temperature can be transferred from the diborane generation flask to a new flask which contains the molecule to be reduced. Both of these methods are a very economical way of generating diborane. Diborane will form stable complexes with Lewis bases such as ethers, thioethers, and amines to form borane Lewis acid base complexes. The chemistry of these complexes has been published and is outside of the scope of this digest. Precaution: Diborane is a highly toxic gas at room temperature and should be handled with appropriate care. 8) Enantioselective reduction using sodium borohydrides Normally alkali and alkaline earth borohydrides by them self cannot enantioselectively reduce organic functional groups. There are a few exceptions to this rule where the alkali or alkaline earth cation complexes with the compound in such a manner as to stericlly direct the approach of the borohydride to
*For Online Consulting Only
press -F for Searching
20
the functional group to be reduced therefore forming only one conformer. (129) Another method that works on the premise of controlling the steric availability of functional group to the reducing agent is the use of molecules that associates with the substrate in such a manner as to sterically direct the borohydride to react with only one face of the reducible functional group. A prime example of this technique is cyclodextrin. The molecule of interest can enter the cavity of the cyclodextrin molecule and due to steric restraints imposed by the cyclodextrin molecule only one face of the reducible functional group is accessible to the borohydride reducing agent. (130-131) Enantioselective reductions can be achieved using sodium borohydride by adding chiral modifying reagents such as enantiomerically pure; chiral alcohols, chiral carboxylic acids, sugars, tartaric acids and other chiral organic compounds to the borohydride prior to reaction with the substrate. These reagents have been shown to give high ee’s. (55-65) Chiral transition metal catalyst such as the cobalt catalyst developed by Yamada et al. can catalytically reduce functional groups such as ketones, imines and oximes by using the sodium borohydride as a source of hydride. (102-106) Many borane based chiral reducing reagents and catalyst that are formed from and use diborane as a source of
Rohm and Haas : the Sodium Borohydride Digest
hydrides are synthesized from borohydrides (see above). Many reviews using these reagents have been published. (132-138) 9) Chemoselectivity As a general rule the reactivity of sodium borohydride towards organic functional groups at room temperature is as follows: Easily reduced Aldehydes>> Ketones> Acid Chlorides = Imines = >C=N+< Moderately reduced Esters, Epoxides, Lactones Difficult to reduce: Carboxylic Acids, Amides, Imides, Carbinol, Nitrile, Nitro Dehalogenantion, Tosylehydrazone, Hydroboration and C-Calcogen Bond Cleavage The selectivity of sodium borohydride can be attributed to the inherent reductive strength of sodium borohydride itself. This reductive strength can be modified by adding co-reagents that either transforms or modify the boron hydride bond or by changing the kinetic properties of the reductive system, such as temperature or time of reaction.
*For Online Consulting Only
press -F for Searching
21
Modifiers which increase the reductive strength of sodium borohydride by decreasing the bond strength between boron and hydrogen while the borohydride keeps all four of it’s hydrides are metal salts such as LiCl, ZnCl2, CaCl2, AlCl3 , N(Bu)4 and others. (66-82, 90-92) Sodium borohydride can be transformed into a stronger reducing agent by adding modifiers that cause the sodium borohydride to loss between 1 and three hydrogens to form NaBH3OR or NaBH(OR)3. These modifiers are usually small molecular weight alcohols and carboxylic acids. (55-56) Another method of increasing the reductive strength of sodium borohydride is to increase the temperature of the reaction. This accomplishes two things it increases the rate of the reaction and also adds energy to system to overcome the ∆ G of the reaction. These different methods of increasing the reactivity of sodium borohydride can be and are usually used in combination to accomplish many reductions that are not possible with sodium borohydride alone.
Rohm and Haas : the Sodium Borohydride Digest
References: 1) Davis, W.D.; Mason, L.S.; Stegeman, G J. Am. Chem. Soc. 1949, 71, 2774; Chem. Abstr. 43, 7805d 2) Douglas, T.; Harman, A.W. J. Res. Nat. Bur. Std. 1958, 60, 117; Chem. Abstr, 52, 10704I 3) Stockmayer, W.H.; Rice, D.W.; Stephanson, C.C. J. Am. Chem. Soc. 1955, 77, 1980; Chem. Abstr, 49, 9361d 4) Johnston, H.L.; Hallet, N.C., J. Am. Chem. Soc. 1953, 75, 1467; Chem. Abstr, 47, 10331e 5) Havery, K.B.; McQuaker, N.R. Can. J. Chem. 1971, 49, 3272 6) Jensen, E.H. "A Study on Sodium Borohydride", NytNordisk Forlag Amold Busck, Copenhagen 1954- (Out of Print) 7) Gardiner, J.A.; Collat, J.W. J. Am. Chem. Soc. 1965, 87, 1692; Chem. Abstr, 62, 13899b. 8) Gardiner, J.A.; Collat, J.W. Inorg. Chem. 1965, 4, 1208; Chem. Abstr, 63, 6610e 9) Wang, F.T.; Jolly, W.L. Inorg. Chem. 1972, 11, 1933; Chem. Abstr, 77, 93285z 10) Levine, L.A.; Kreevoy, M.M. J. Am. Chem. Soc. 1972, 94, 3346; Chem. Abstr, 77, 10408t 11) Kreevoy, M.M.; Hutchins, J.E.C. J. Am. Chem. Soc. 1972, 94, 6731; Chem. Abstr, 77, 118776a
*For Online Consulting Only
press -F for Searching
22
12) Abts, L.M.; Langland, J.T. Kreevoy, M.M., J. Am. Chem. Soc. 1975, 97, 3181; Chem. Abstr, 83, 121307c 13) Prokopcikas, A Salkauskiene, J. Zh. Fiz. Khuim. 1970, 44, 2941; Chem Abstr, 74, 46077m 14) Mochalov, K.N.; Khain, V.S.; Gil'manshin, G.G.; KInetika I Kataliz 1965, 6, 541, Chem. Abstr, 63, 17202b 15) Paul, R.E.; Buisson, P.J.; Joseph, N.M. Ind. Eng. Chem. 1952, 44, 1006, Chem. Abstr, 46, 9960e 16) Schlesinger, H.I. et. al. J. Am. Chem. Soc. 1953, 75, 215; Chem Abstr, 47, 3742e 17) Levy, A; Brown, J.B.; Lyons, C.J. Ind. Eng. Chem. 1960, 52, 211; Chem. Abstr, 56, 4360h 18) Brown, H.C.; Brown, C.A. J. Am. Chem. Soc. 1962, 84, 1493; Chem. Abstr, 57, 111b 19) Prokocikas, A.; Valsiuniene, J; Kimtiene, D. Liet. TSR Mokslu Akad. Darb, Ser. B 1970, 27; Chem. Abstr, 75, 10760k 20) Prokocikas, A.; Salkauskiene, J. Liet. TSR Mokslu Akad. Darb, Ser. B 1971, 3; Chem. Abstr, 74, 146745w 21) Prokocikas, A.; Valsiuniene, J Liet. TSR Mokslu Akad. Darb, Ser. B 1971, 13 Chem. Abstr, 75, 10767t 22) Holbrook, K.A.; Twist, P.J. J. Chem. Soc. A 1971, 890; Chem. Abstr, 74, 116413u 23) Kaufman, C.M.; Sen, B. J. Chem. Soc. Dalton Trans. 1985, 307; Chem. Abstr, 102, 17327q
Rohm and Haas : the Sodium Borohydride Digest
24) Brown, H.C.; Ichikawa, K.J. J. Am. Chem. Soc. 1961, 83, 4372; Chem. Abstr, 56, 7117c 25) Brown, H.C.; Mead, E.J.; Subba Roa, B.C. J. Am. Chem. Soc. 1955, 77, 6209; Chem. Abstr, 50, 8529h 26) Chem. and Eng. News, p 4 Spet 24, 1979 27) French 1,573,705 1969, Chem. Abstr. 72, 1000089q 28) Vicek, A.A.; Rusina, A Proc. Chem. Soc. 1961, 161; Chem. Abstr, 56, 7186I 29) Neilson, T; Wood, H.C.S.; Wylie, A.G. J. Chem. Soc. 1962, 371; Chem. Abstr, 56, 15391b 30) Rickborn, B; Wuesthoff, M.R. J. Am. Chem. Soc. 1970. 92, 6894; Chem. Abstr, 73, 31417y 31) Wigfield, D.C.; Gowland, F.W. Tetrahedron Lett. 1976, 3373; Chem. Abstr, 86, 71391q 32) Wigfield, D.C.; Gowland, F.W. J. Org. Chem. 1977, 42, 1108; Chem. Abstr. 86, 12047b 33) Wigfield, D.C.; Gowland, F.W. Can. J. Chem. 1987, 56, 786; Chem. Abstr. 87, 133739r 34) Wigfield, D.C. Tetrahedron 1979, 35, 449 35) Cram, D.J.; Wilson D.R. J. Am. Chem. Soc. 1963, 85, 1245 36) Cram, D.J.; Greene, F.D. J. Am. Chem. Soc. 1953, 75, 6004 37) Cherest, M.; Felkin, H.; Prudent, N. Tetrahedron Lett. 1968, 18, 2199
*For Online Consulting Only
press -F for Searching
38) 39) 40) 41) 42) 43) 44) 45) 46) 47) 48) 49)
23
Anh, N.T. Top. Curr. Chem. 1980, 88, 145 Ahn, N.T.; Eisenstein, O. Nouv. J. Chem. 1977, 1, 61 Ahn, N.T.; Eisenstein, O. Tetrahedron Lett. 1976, 3, 155 Cram, D.J.; Elhafez F.A.A. J. Am. Chem. Soc. 1952, 74, 5828 Louis-Andre, O; Gelbard, G. Tetrahedron Lett. 1985, 26, 831; Chem. Abstr. 103, 37624c Lamaty, G.; Riviere, M.H.; Roque, J.P. Bull. Soc. Chim. Fr. 1983, 33; Chem. Abstr. 95, 80246j D'Incan, E.; Loupy, A. Tetrahedron 1981, 37, 1171; Chem. Abstr. 95, 80246j Julia, S.; Ginebreda, A.; Guixer, J; Masama, J.; Tomaas, A.; Colonna, S. J. Chem. Soc., Perkin Trans 1, 1981, 574, Chem. Abstr. 94, 191536c Raber, D.J.; Guida, W.C.; Schoenberger, D.C. Tetrahedron Lett. 1981, 22, 5107; Chem. Abstr. 96, 162074m Montanari, F.; Rundo, P. J. Org. Chem. 1981, 46, 2125; Chem. Abstr. 94, 191216y D'Antone, S.; Penco, M.; Solaro, R. Reactive Polymers 1985, 3, 107; Chem. Abstr. 103, 88267w Kondo, S.; Nakanishi, M.; Tsuda, K. J. Polymer Sci.; Polymer Chem. Ed. 1985, 23, 581; Chem. Abstr. 103, 36794w
Rohm and Haas : the Sodium Borohydride Digest
50) D'Antone, S.; Solaro, R.; Penco, M.; Chiellini, E. Conv. Ital. Sci. Macrmol., [atti], 6th 1983, 2, 318; Chem. Abstr. 101, 56147z 51) Kondo, S.; Nakanishi, M.; Yamane, K.; Horibe, A.; Tsuda, K. J. Appl. Poly. Sci. 1986, 32, 4255; Chem. Abstr. 105, 191638h 52) Masse, J.P.; Parayre, E.R. J. Chem. Soc. Chem. Commun. 1976, 438; Chem. Abstr. 85, 192270h 53) Horner,L.; Brich, W. Liebigs Ann. Chem. 1978, 710; Chem. Abstr. 89, 128818c 54) Kinishi, R.; Nakajima, Y.; Oba, J.; Inouye, Y. Agric. Biol. Chem. 1978, 42, 869; Chem. Abstr. 89, 106932h 55) Gribble, G.W. Chem. Soc. Review 1998, 27, 395 56) Gribble, G.W. ACS Symposium Series 1996, 641, 167 57) Yamada, S.; Mori, Y.; Morimatsu, K.; Ishizu, Y.; Ozaki, Y.; Yoshioka, R.; Nakatani, T.; Seko, H. J. Org. Chem. 1996, 61, 8586 58) Sharma, L. Indian. J. Chem. 1997, 36B, 796 59) Sharma, L.; Singh, S. Indian J. Chem. 1994, 33B, 1183 60) Zhdanov, V.A.; Alekseev, Y.E.; Korol, E.L.; Sudareva, T.P.; Alekseeva, V.G. Russ. J. Gen. Chem. 1993, 63, 1045
*For Online Consulting Only
press -F for Searching
24
61) Morrison, J.D.; Gradbois, E.R.; Howard, S.I. J. Org. Chem. 1980, 45, 4229 62) Hirao, A.; Nakahama, S.; Mochizuki, H.; Itsuno, S.; Yamazaki, N. J. Org. Chem. 1980, 45, 4231 63) Yatagai, M.; Ohnuki, T. J. Chem. Soc. Perkin Trans. 1 1990, 1826 64) Bianch, G.; Achilli, F.; Gamba, A.; Vercesi, D. J. Chem. Soc. Perkin Trans 1 1988, 417 65) Yatagai, M; Ohnuki, T. J. Chem. Soc. Perkin Trans. 1 1990, 1826 66) Wong, S.S.; Paddon-Row, M. N. J. Chem. Soc. Chem. Commun. 1990, 546 67) Zhang, H.C.; Costanzo, M.J.; Maryanoff, B.E. Tetrahedron Lett. 1994, 35, 4891 68) Helm, R.F.; Ralph, J. J. Wood Chem. Tech. 1993, 13, 593 69) Narasimhan, S.; Madhavan, S.; Prasad, K.G. Synth. Commun. 1997, 27, 385 70) Narasimhan, S.; Madhavan, S.; Balakumar, R.; Swarnalakshmi, S. Synth. Commun. 1997, 27, 391 71) Bhattacharyya, S. Organometallic 1996, 15, 1065 72) Bhattacharyya, S.; Chatterjee, A.; Williamson, J.S. Synth. Commun. 1997, 27, 4265 73) Bhattacharyya, S. Synth. Commun. 1995, 25, 2061 74) Narasimhan, S.; Madhavan, S.; Prasad, K.G. J. Org. Chem. 1995, 60, 5314
Rohm and Haas : the Sodium Borohydride Digest
75) Kim, S.; Oh, C.H.; Ko, J.S.; Ahn, K.H.; Kim, Y.J. J. Org. Chem. 1985, 50, 1927 76) Ranu, B.C.; Jana, U.; Sarkaar, A. Synth. Commun. 1998, 28, 485 77) Narasimhan, S.; Madhavan, S.; Prasad, K.G. Synth. Commun. 1996, 26, 703 78) Ranu, B.C.; Sarkar, A.; Chakraborty, R. J. Org. Chem. 1994, 59, 4114 79) Bhattacharyya, S.; Chatterjee, A.; Duttachowdhury, S.K. J. Chem. Soc. Perkin Tran. 1 1994, 1 80) Liu, Y.; Schwartz, J. Tetrahedron 1995, 51, 4471 81) Liu, Y.; Schwartz, J. J. Org. Chem. 1994, 59, 940 82) Dosa, P.; Kronish,I; McCallum, J.; Schwartz, J.; Barden, M.C. J. Org. Chem. 1996, 61, 4886 83) Bhattacharyya S. J. Org. Chem. 1995, 60, 4928 84) Bhattacharyya S. Tetrahedron Lett. 1994, 35, 2401 85) Armstrong, J.D.; Wolfe, C.N.; Keller, J.L.; Lynch, J.; Bhupathy, M.; Volante, R.P. Tetrahedron Lett. 1997, 1531 86) Barden, M.C.; Schwartz, J. J. Org.Chem. 1995, 60, 5963 87) Barros, M.T.; Alves, C.M.; Santos, A.G.; Godinho, L.S.; Maycock, C.D. Tetrahedron. Lett. 1995, 36, 2321
*For Online Consulting Only
press -F for Searching
25
88) Masaguer, C.F.; Bleriot, Y.; Charlwood, J.; Winchester, B.G.; Fleet, G.W.J. Tetrahedron, 1997, 55, 15147 89) Taniguchi, M.; Fujii, H.; Oshima, K.; Utimoto, K. Tetrahedron, 1995, 51, 679 90) Teixeira, L.H.; Barreriro, E.J.; Fraga, C.A.M. Synth. Commun. 1997, 27, 3241 91) Narasimhan, S.; Ganeshwar, K.; Madhavan, S. Tetrahedron Lett. 1995, 36, 1141 92) Molander, G.A. Chem. Rev. 1992, 92, 29 93) Falorni, M.; Porcheddu, A.; Taddei, M. Tetrahedron. Lett. 1999, 40, 4395 94) McGeary, R.P. Tetrahedron Lett. 1998, 39, 3319 95) Ravichandran, R.; Divakar, S. J. Mol. Catal. A. 1999, 137, 31 96) Pichumani, K.; Velusamy P.; Srinivasan, C. Tetrahedron, 1994, 45, 12979 97) Goldberg, Y.; Abele, E.; Rubina, K.; Popelis, Y; Shimanska, M. Chem. Heterocyclic Comp. 1993, 29, 1399 98) Fornasier, R.; Lucchini, V.; Scrimm, P.; Tonellato, U. J. Org. Chem. 1986, 51, 1769 99) Sakuraba, H.; Inomata,N. Tanaka, Y. J.Org. Chem. 1989, 54, 3482 100) Fornasier, R.; Reniero, F.; Scrimm, P.; Tonellato, U. J. Org. Chem. 1985, 50, 3209 101) Nagata, T.; Sugi, K.D.: Yamamda, T.; Mukaiyama, T. Synlett. 1996, 1076
Rohm and Haas : the Sodium Borohydride Digest
102) Sugi, K.D.; Nagata, T.; Yamamda, T.; Mukaiyama, T. Chem. Lett. 1997, 493 103) Sugi, K.D.; Nagata, T.; Yamamda, T.; Mukaiyama, T. Chem. Lett. 1996, 737 104) Sugi, K.D.; Nagata, T.; Yamamda, T.; Mukaiyama, T. Chem. Lett. 1996, 1081 105) T. Mukaiyama, T. Nagata, K. Yorozu, T. Yamada Angew. Chem. Int. Ed. Engl., 1995, 34, 2145 106) Itsuno, S. Organic Reactions 1998, 52, 395 107) Vyskocil, S.; Smrcina, M.; Hanus, V.; Polasek, H.; Kocovsky, P. J. Org. Chem. 1998, 63, 7738 108) Abiko, A.; Masamiune, S. Tetrahedron Lett. 1992, 33, 5517 109) Verardo, G.; Giumanini, A.G.; Strazzolini, P.; Poiana, M. Synthesis 1993, 121 110) Verardo, G.; Giumanini, A.G.; Strazzolini, P. Synth. Commun. 1994, 24, 609 111) Prasa, A.S.B.; Kanth, J.V.b.; Periasamy, M. Tetrahedron, 1992, 48, 4623 112) K. Drauz et al. (Degussa); US Pat 5585500, 17 Dec. 1996 113) Prasa, A.S.B.; Kanth, J.V.b.; Periasamy, M. Tetrahedron, 1992, 48, 4623 114) Barby, D.; Champagne, P. Synth. Commun. 1995, 25, 3503
*For Online Consulting Only
press -F for Searching
26
115) Das, B.; Kashinatham, A.; Madhusudhan, P. Tetrahedron Lett. 1998, 39, 677 116) Prasa, A.S.B.; Kanth, J.V.B.; Periasamy, M. Tetrahedron, 1992, 48, 4623 117) J. V. B. Kanth and M. Periasamy, J.Org. Chem. 1991, 56, 5964 118) J. W. Simek et al., J. Chem. Ed. 1997, 74, 107 119) A. I. Meyers, K. Drauz et al., J. Org. Chem. 1993, 58, 3568 120) Giannis, A.; Sandoff, K. Angew. Chem. Int. Ed. Engl.. 1989, 28, 218 121) Dharanipragada, R.; Alarcon, A.; Hruby, V. J. Org. Prep. Prac. Int. 1991, 23, 396 122) Kabno, S.; Tanaka, Y.; Sugino, E.; Hibino, S. Synthesis 1980, 695 123) Barney, C.L.; Huber, E.W.; McCarthy, J.R. Tetrahedron Lett. 1990, 31, 5547 124) Boesten, W.H.; Schepers, C.H.M.; Roberts, M.J.A. EPO 322982 A2 1989 125) Tone, H.; Nishi, T.; Oikawa, Y.; Hikota, M.; Yonemitsu, O. Tetraherdron Lett. 1987, 28, 4569 126) Taber, D.F.; Houze, J.B. J. Org. Chem. 1994, 59, 4004 127) Sengupta, S.; Sahu, D.P.; Chatterjee, S.K. Indian J. Chem. 1994, 33b, 285 128) Bott, S.G.; Marchand, A.P.; Bolin, J.; Xing, D.; Talafuse, L.K. J. Chem. Crystallgraphy 1995, 25, 657
Rohm and Haas : the Sodium Borohydride Digest
129) Fornasier, R.; Reniero, F.; Scrimin, P.; Tomellato, U. J. Org. Chem. 1985, 50, 3209 130) Gol’dberg, Y.; Abele, E.; Rubina, K.; Popelis, Y.; Shimanska, M. Chem. Hetero. Compounds 1993, 29, 1399 131) Pelter, A.; Smith, K.; Borwn, H.C. Borane Reagents” 1988, acedemic press London 132) Abdel-Mgid, A.F. ACS Symposium Series 1996, vol 641 133) Corey, E.J. Helal, C.J. Angew. Chem. Int. Ed. 1998, 37, 1986 134) Midland, M.M. Chem. Rev. 1989, 89, 1553 135) Brown, H.C.; Jadhav, P.K.; Mandal, A.K. Tetrahedron 1981, 37, 3547 136) Pelter, A.; Smith, K. Comprehensive Organic Chemistry 1973, 3, 695 137) Ager, D.J.; Prakash, I.; Schaad, D.R. Chem. Rev. 1996, 96, 835
*For Online Consulting Only
press -F for Searching
27
Rohm and Haas : the Sodium Borohydride Digest
C. Carbonyl Coumpounds ALDEHYDES Alembic 18, 32, 48, 50, 52, 55, 58
The use of NaBH4 for the reduction of aldehydes to the corresponding primary alcohol is well known. The reductions proceed rapidly, and in most cases quantitatively in water, lower alcohols, amines and a variety of other organic solvents : 4 RCHO + NaBH4 Æ NaB(OCH2R)4 Æ 4 RCH2OH
Jensen (1) has shown that NaBH4 can quantitatively reduce the following aldehydes in a water/dioxane solvent system within two minutes at room temperature. Formaldehyde Acetaldehyde Paraformaldehyde propionaldehyde butylradehyde isobutyraldehyde isovaleraldehyde 4- chlorobenzaldehyde Crotonaldehyde anisaldehyde
Aldol benzaldehyde phenylacetaldehyde 4-tolualdehyde naphthaldehyde 2-ethoxybenaldehyde 2-chlorobenzaldehyde hexanal methacrylaldehyde glyceraldehyde
*For Online Consulting Only
press -F for Searching
28
While NaBH4 can reduce nearly all aldehydes the reduction rate depends upon the concentration of the solvent used and the reaction temperature. Reduction is generally rapid and quantitative in aqueous media. Kinetic studies of carbonyl compounds reduction in water DMSO and water/DMSO mixtures indicate that the reaction obeyed second order kinetics and that the rate constants increased with increasing water contents (2). Room temperature reductions of aldehydes (and ketones) in twophase systems, i.e. Et2O/aq. NaBH4, have resulted in excellent yields of the corresponding alcohol (3). Water-soluble bisulfite adducts of aldehydes can be formed to facilitate NaBH4 reduction in aqueous media (4). Electron-Withdrawing substituents that increase the fractional positive charge on the carbonyl carbon accelerate the reduction rate while electron- donating substituents have the opposite effect. This high reactivity with NaBH4 enables one to selectively reduce aldehydes in the presence of other functional groups that are reducible under more vigorous reaction conditions. For example, the reactivity of aldehydes with NaBH4 is considerably greater than that of ketones. Because of this difference in reactivity of the two carbonyl groups, it is possible to carry out the selective reduction of
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest
aldehyde groups in the presence of keto groups, providing a micromethod for distinguishing between these two types of carbonyl compounds (5). Luche demonstrated an example of the reverse selectivity, that the use of 1 mole equivalence of CeCl3 will retard the reduction of an aldehyde group in the presents of both cyclic and acyclic ketone. (6) Competitive reaction studies of aldehydeketone mixtures with NaBH4 have demonstrated the enhanced reactivity with both aliphatic and aromatic aldehydes with respect to the corresponding ketone (7). The addition of thiol compounds can further enhance the selectivity (8). The selectivity of NaBH4 for aldehydes over ketones was utilized to reduce aldehydic substituents on benzopyranopuyridines to the corresponding alkanols without affecting the keto group (9) and the synthesis of hycanthone (10). O
NH(CH2)2NEt2
O
NH(CH2)2NEt2
NaBH4
C
H
O
*For Online Consulting Only
H
C OH
H
29
NaBH4 reduction of aldehydes has been used as a “blocking” technique to prevent Schiff base staining in histology work (11). Chemoselective reduction of aldehydes in the presence of ketones is greatly enhanced by employing acyloxyborohydrides formed from sodium borohydride and a lower aliphatic carboxylic acid, as reported by Gribble and coworkers. The reagent, e.g. NaBH(OAc)3, can either be formed in situ or prepared separately before use (12). The corresponding tetrabutylammonium salt, Bu4NBH(OAc)3 that can be made readily at room temperature, has also been reported (13).
Rohm and Haas : the Sodium Borohydride Digest
The specificity of NaBH4 for carbonyl groups makes it possible to reduce aldehydes in the presence of the following functional groups: Functional group carbonyl ester lactone lactam imide acetate nitrile nitro amine oxide olefin epoxy tosyl ester haloalkyl or aryl thiocarbonyl amide acetylenes
References 14,15 16-21 22-24 25 26-27 22,28 17,24,29 30. 31 32 17,18,27,32-36, 28,34 38 18,39-41 40 42 43-48
Because of its selectivity and rapidity in aldehyde reductions, NaBH4 has been used extensively in the synthesis of steroids (37), carbohydrate derivatives (49-53), insecticides (54,55), perfume
*For Online Consulting Only
press -F for Searching
30
ingredients (56-58), in the reduction of Vitamin A aldehyde (59) and in the production of other pharmaceuticals such as dihydrostreptomycin (60-63), antihypertensives (65), antiviral (66) and antithrombotic (67) drugs. The mild reaction conditions employed in NaBH4 reduction of aldehydes favor retention of stereochemical configuration (65,68). In some instances, lactones can be formed during NaBH4 reduction of aldehydes located α or β to carboxylate groups (69,70). Similarly, ozonolysis of unsaturated ketones followed by NaBH4 reduction can lead to formation of δlactones (71). Periodate cleavage of vicinyl diols followed by NaBH4 reduction of the resulting dialdehyde has been utilized to characterize polysaccharides and in the preparation of lividomycin B derivatives (72). A related cleavage/reduction reaction, ozonolysis followed by NaBH4 reduction, was employed in the total synthesis of camptothecin from acridine (73). The use of aprotic solvents such as hexane as a reaction solvent for the sodium borohydride reduction of aldehydes has recently been demonstrated. Either aromatic or aliphatic aldehydes were combined with hexane in the presents of silica gel and sodium borohydride to give the corresponding alcohols in high yield. (74) The use of tetraalkyl ammonium chloride (75) or crown ethers for the reduction of aldehydes with sodium
Rohm and Haas : the Sodium Borohydride Digest
borohydride in phase transfer catalysis systems is a well established technique. (76) (Alembic 52, 55) Recently polyethylene gycol has been used as a phase transfer reagent in the reduction aldehydes with sodium borohydride. This methodology has the advantage over previous phase transfer reagent in that PEG is relatively cheap reagent in comparison to traditional phase transfer reagents such as crown ethers, polyethers or onium salts. (77). (Alembic 56) A very important technique for the reduction of aldehydes with sodium borohydride is the impregnation of solid supports such as polymer (78), ion exchange resins (78, 79) (Alembic 52) and zeolite (80) with borohydrides. (Alembic 58) Many different metal borohydrides such as Zn (77, 81) and Cu (79) have also been used in cooperation with solid supports to achieve high yield reductions of aldehydes to alcohols and alkanes. Polymeric zinc borohydride with organic nitrogen compounds will reduce aldehydes selectively. (82) References: 1) Jensen, E.H. “A Study on Sodium Borohydride”, Ny Nordisk, Forlag, Arnold Busck, Copenhagen 1954 (out of Print.)
*For Online Consulting Only
press -F for Searching
31
2) Adams, C.; Gold, V.; Reuben, D.M.E.; J. Chem. Soc., Perkin 2 1977, 1466; Chem. Abstr. 88, 36933n 3) Chung, J.S. Tackan Hwahak Heochi 1974, 18, 363; Chem. Abstr. 82, 111712w 4) Jpn. Kokai, 74117,458 1974; Chem. Abstr. 83, 976v 5) Critchley, J.P.; Friend, J.; Swain, T. Chem. and Ind. 1958, 598; Chem. Abstr. 53, 983c 6) Luche, J.L.; Gemal, J.A. J. Amer. Chem. Soc. 1979, 101, 5848 7) Sell, C.S. Aust. J. Chem. 1975, 28, 1383; Chem. Abstr. 83, 163088n 8) Maki, Y. Terahedron Lett. 1977, 263; Chem. Abstr. 87, 22620a 9) Jpn. Kokai, 7652,199, 1976; Chem. Abstr. 85, 192694d 10) Laidlaw, G.M.; Collins, J.C.; Archer, S.; Rosi, D.; Schulenberg, J.W. J. Org. Chem. 1973, 38, 1743; Chem. Abstr. 78, 159373f 11) Lillie, R.D.; Pizzolato, P. Stain Technology 1973, 47, 13; Chem. Abstr. 76, 32058k 12) Gribble, G.W.; Feerguson, D.C. J. Chem. Soc. Chem. Commun. 1975, 535; Chem. Abstr. 83, 131278h 13) Nutaitis, C.F.; Bribble, G.W. Tetrahedron Lett. 1983, 24, 4287; Chem. Abstr. 49, 3075g 14) Brown, J.J.; Newbold, G.T. J. Chem. Soc. 1953, 3648; Chem. Abstr. 49,3075g
Rohm and Haas : the Sodium Borohydride Digest
15) Stutz, E.; Deuel, H. Helv. Chim. Acta 1956, 39, 2126; Chem. Abstr. 51,50334b 16) Morrison, A.L.; Long, R.F. J. Chem. Soc. 1958, 211; Chem. Abstr. 52,11035h 17) Remers, W.A.; Roth, R.H.; Wweiss, M.J.J. Am. Chem. Soc. 1964, 86, 4612; Chem. Abstr. 61, 1604d 18) Sciaky, R.; Mancini, F. Tetrahedron Lett. 1965, 137; Chem. Abstr. 62, 10475g 19) Brit. I,266,093 1972; Chem. Abstr. 76, 153599w 20) De Koning, H.; Subramaanian-Erhart, K.E.C. Syn. Commun. 1973, 3,25; Chem. Abstr 78,135587c 21) Grieco, P.A.; Nishizawa, M.; Oguri, R.; Burke, S.D.; Marinovic, N. J. Am. Chem. Soc. 1977, 99, 5773; Chem. Abstr. 87, 184712j 22) Golab, T.; Trabert, C.H.; Jaeger, H.; Reichstein, T. Helv. Chim. Acta 1959, 42, 2418; Chem. Abstr. 55, 27407a 23) Chernobai, V.T.; Kolesnikov, D.G. Proc. Acad. Sci. USSr (Engl. Trans.) 1959, 127, Chem. Abstr. 53,20696c 24) Ger. Offen. 2,142,842; Chem. Abstr. 77, 48245a 25) Fall, H.H.; Petering, H.G.; J. Am. Chem. Soc. 1956, 78, 377; Chem. Abstr. 50, 13038i 26) Schoeberl, A; Pape, C.V. Chem. Ber. 1965, 98, 1688; Chem. Abstr. 63, 4383c
*For Online Consulting Only
press -F for Searching
32
27) Danishefsky, S.; McKee, R.; Singn, R.K. J. Am. Chem. Soc. 1977, 99, 4783; Chem. Abstr. 87, 184743v 28) Moreau, S.; Cacan, M.; Lablanche-Combier, A.; J. Org. Chem. 1977, 42, 2632; Chem. Abstr. 87, 65069s 29) Milijkovic, D.; Petrovic, J. J. Org. Chem. 1977, 42, 2101; Chem. Abstr. 87, 23595h 30) Schechter, H.; Ley, D.E.; Zeldin, H. J. Am. Chem. Soc. 1952, 74, 3664; Chem Abstr. 47, 5885c 31) Salgado, A.; Huybrechts, T.; De Buyck, L.; Czombos, J.; Tkachev, A.; De Kimpe, N. Synth. Commun. 1999, 29, 5763 32) Dirlam, J.P.; McFarland, J.W. J. Org. Chem. 1977, 42, 1360; Chem. Abstr. 86, 155694z 33) Eldelson, J. Et. Al. J. Am. Chem. Soc. 1959, 81, 5150; Chem. Abstr. 54, 7548b 34) Klein, E.; Rojahn, W.; Henneberg, D. Tetrahedron 1964, 20, 2025; Chem. Abstr. 61, 14716h 35) Ger. Ofen. 2,513,996 1976; Chem. Abstr. 86, 16353d 36) Ger. Offen. 2,559,433 1976; Chem. Abstr. 86, 55066g 37) U.S. 4,544,555 1985; Chem. Abstr. 105, 43157k 38) Dale, W.J.; Hennis, H.E.; J. Am. Chem. Soc. 1956, 78, 2543; Che. Abstr. 51, 1080a 39) Brink, M. Acta Chem. Scand. 1965, 19, 255; Chem. Abstr. 62, 14544d 40) Hull, R.; Van der Brock, P.J.; Swain, M.L. J. Chem. Soc. Perkin 1 1975, 2271; Chem. Abstr. 84, 89960t
Rohm and Haas : the Sodium Borohydride Digest
41) Ger. Offen. 2,064,106 1972; Chem. Abstr. 77, 101126r 42) Fr. Demande 2,260,332 1971; Chem Abstr. 84, 89999n 43) Ger. Offen. 2,065,014 1971; Chem. Abstr. 76, 59435t 44) Jpn. 72,03,342 1972; Chem. Abstr. 76, 126766s 45) Jpn. 73,32,108 1973; Chem. Abstr. 80, 47827s 46) Jpn. 74 13 778 1974; Chem. Abstr. 81, 151982v 47) Jpn. Kokai 75 25, 539 1975; Chem. Abstr. 83, 131442g 48) Parry, R.J.; Kunitani, M.G. J. Am. Chem. Soc. 1976, 98, 4024; Chem. Abstr. 85, 89917e 49) Wolfrom, M.L.; Anno, K. J. Am. Chem. Soc. 1952, 74, 5583; Chem. Abstr. 101, 73033b 50) Morin, C. Carbohydr. Res. 1984, 128, 345; Chem.Abstr. 101, 73033b 51) Sinhabau, A.K.; Barle, R.l.; Pochopin, N.; Borchardt, R.T. J. Am. Chem. Soc. 1985, 107, 7628; Chem. Abstr. 013, 209794b 52) Usuki, S.; Nagai, Y Anal. Biochem. 1986, 152; Chem. Abstr. 014, 48213q 53) Williams, A.G.; Withers,S.E. J. Microbiol. Methods 1986, 4, 277; Chem. Abstr. 105, 75147y 54) Eur. Pat. Appl. 50,857 1982; Chem. Abstr. 97, 144560h
*For Online Consulting Only
press -F for Searching
55) 56) 57) 58) 59) 60) 61) 62) 63) 64) 65) 66) 67) 68) 69) 70)
33
Ger. Offen. 3,402,483 1984; Chem. Abstr. 102, 24273s Eur. Pat. Appl. 53, 716 1982; Chem. Abstr. 97, 216516y U.S. 4,521,634 1985; Chem. Abstr. 104, 6053g Eur. Pat. Appl. 184, 7078 1986; Chem. Abstr. 105, 178244g Brit. 778,753 1957; Chem. Abstr. 52,2077I U.S. 3,397,197, 1968; corresponds to Brit 1,063,450 1967; Chem. Abstr. 68, 22212b Kaplan, M.A.; Fardig, O.B.; Hopper, I.R. J. Am. Chem. Soc. 1954, 76, 5161; Chem. Abstr 49, 20876I U.S. 2,790,792 1957; Chem. Abstr. 51, 15561d U.S.; 2,945,850 1960; Chem. Abstr. 54, 23211I Jpn. Kokai Tokkyo Koho 83, 140,032 1983; Chem. Abstr. 100, 22323t Arigoni, D.; Battagila, R.; Akhtar, M.; Smith, T. J. Chem., Chem. Commun. 1975, 185; Chem. Abstr. 83, 2961b U.S. 5,233,041 1993 U.S. 5,767,269 1998 Jpn. Kokai Tokkyo Koho 85, 146,840 1985; Chem. Abstr. 104, 33760s Spry, D.O. J. Org. Chem. 1975, 40, 2411; Chem. Abstr. 83, 97171f Bowen, D.H.; Cloke, C.; Harrison, D.M.; MacMillan, J. H. J. Chem. Soc., Perkin 1 1975, 83; Chem. Abstr. 82, 140326d
Rohm and Haas : the Sodium Borohydride Digest
71) Chavdarian, C.G.; Heathcock, C.H. J. Org. Chem. 1975, 40, 2970; Chem. Abstr. 83, 179317x 72) Jpn. 76,11,611 1976; Chem. Abstr. 86, 5774r 73) Corey, E.J.; Crouse, D.N.; Anderson, J.E. J. Org. Chem. 1975, 40, 2140; Chem. Abstr. 83, 79450s 74) Yakabe, S.; Hirano, M.; Morimoto, T. Synth. Commun. 1999, 29, 295 75) Stark, C.M.; Liotta, C.L.; Halpern, M. Phase Transfer Catalysis: Fundamentals, Applications and industrial Perspectives; Chapman and Hall; New York, 1994 76) Blanton, J.R. Synth. Commun. 1997, 27, 2093 77) Tamami, N.; Goudarzian, N.; Kiasat, A.R. Eur. Polym. J. 1997, 33, 977 78) Bandgar, B.P.; Kshirsagar, .N.; Wadgaonkar, P.P. Synth. Commun. 1995, 25, 941 79) Sim, T.B.; Yoon, N.M. Bull. Chem. Soc. Jpn. 1997, 70, 1101 80) Sreekumar, R.; Padmakumar, R.; Rugmini, P. Tetrahedran Lett. 1998, 39, 5151 81) Tamami, B.; Lakouraj, M.M. Synth. Commun. 1995, 25, 1089 82) Firouzabadi, F.; Zeynizadeh, B. Bull. Chem. Soc. Jpn. 1997, 155
*For Online Consulting Only
press -F for Searching
34
Rohm and Haas : the Sodium Borohydride Digest
KETONES Alembic: 7, 18, 21, 26, 31, 48, 50, 52, 55, 58, 62 Under normal conditions, NaBH4 reduces ketones at a slower rate than aldehydes. While in most cases aldehydes undergo reactions within a few minutes, the reduction of ketones usually takes 30-90 minutes. A few examples of ketones that are reduced at least 90 % at room temperature are: Time required for 90 % Reduction Ketone (min) Acetone 40 3-hydroxy-2-butanone 2 acetophenone 100 benzophenone 130 benzoin 6 cyclopentanone 90 cyclohexanone 4 2-methylcyclohexanone 7 menthone 90 isatin 2 furoin 12 As indicated in the table, α-substituents which increase the fractional positive charge on the carbonyl
*For Online Consulting Only
press -F for Searching
35
carbon enhance the rate of BH4- attack. Of course, many other factors play a part in the rate of reduction. Ring strain and steric effects are also important. Five and six membered cyclic ketones are reduced much more rapidly than more highly strained cyclic(1-4) ketones. The influence of steric effects has been correlated with reduction rates(5). Physico-chemical factors in ketone reductions by NaBH4 are reported by other investigators for unbranched aliphatic ketones (6), cycloalkyl phenyl ketones (7), substituted acetophenones (8), and substituted fluorenones (9,10). The heats of reduction for simple ketones are reported (11). The mechanism and kinetics of ketone reduction by sodium borohydride have been topics of extensive study in recent years, particularly in view of the striking stereochemical control that can be achieved with sodium borohydride. (Alembic 11, 24) Wigfield et. al. (12-18), in a series of elegant studies, have provided a better insight into the mechanisms and transition state in this reaction and a rationale for prediction of stereodirection. It has generally been assumed that the product of ketone reduction is a tetraalkoxyborate formed according to the equation: 4 R2C=O + BH4- Æ (R2CHO)4B-
Rohm and Haas : the Sodium Borohydride Digest
However, Wigfield has clearly shown (12,13) that during ketone reduction in alcoholic solvents, the alcohol plays a crucial role, and that the alkoxy groups are derived from the solvent and not the ketone. Further work (18) using mixtures of NaBH4 and NaBD4 in ketone reductions demonstrated that disproportionation of the monoalkoxy borohydride intermediate does not occur, thus raising doubts as to the validity of the previously proposed (19) completely disproportionation mechanism. Similarly, the evidence for solvent participation and the determination (6) of a kinetic order of 3/2 with respect to 2-propanol in reduction would rule out 4 center and 6 center transition states which have been advocated in the literature, and favor a linear acyclic transition state (20,21) which is product-like in nature. Thus, a stepwise mechanism as previously proposed (22,23), but modified to incorporate the solvent alkoxy group (12,13) has been suggested (18). BH4- + >C=O Æ (RO)BH3- + >CHOH (RO)BH3- + >C=O Æ (RO)2BH2- + >CHOH (RO)2BH2- + >C=O Æ (RO)3BH- + >CHOH (RO)3BH- + >C=O Æ (RO)4B- + >CHOH Measurements of activation parameters in cyclohexanone reductions (15,16) have led to a simple
*For Online Consulting Only
36
press -F for Searching
formula for calculating and predicting stereochemical product ratios (17). Additional work by Wigfield and other on the kinetics of ketone reduction (24-27), transition state analysis (28-32), and steric effects (33-36) have contributed greatly to the current understanding and utility of NaBH4 reductions in organic synthesis. While the rate of ketone reduction is influenced by the solvent, ketone reductions are routinely conducted in a wide variety of organic media as well as in water. Comparative reduction rates for acetone in three solvents are shown below (37) Rate of acetone Reduction in Water, Ethanol and Isopropanol at 0 oC Solvent Water Ethanol Isopropanol
k2x104 (L mol-1 sec-1) 93 97 15.1
Rohm and Haas : the Sodium Borohydride Digest
37
press -F for Searching
Among the many classes of solvents used for sodium borohydride reductions of ketone are: Alkanes Sulfoxides Aromatics Amines Alcohols Carboxylic Acids Ethers Nitroalkanes Nitriles Phosphoramides Amides Water Halocarbons
Rate of Reduction of Acetone with Increasing Temperature in Isopropanol
Phase Transfer Catalysis techniques have been applied successfully to the reduction of ketones with sodium borohydride. (Alembic 55, 56) Several authors (38,40, 40a) have described the asymmetric reductions of ketones using ephedrinium bromides as stereoregulating phase transfer agents. Others have employed lecithin (41), crown ethers (42), and phosphonium salts on silica gel (43) as phase transfer catalysts for ketone reductions. Tetrabutylammonium salts are common phase transfer catalysts (44). Microemulsions have also been used as an alternative to phase transfer catalysis (45). Reduction rate is also influenced by temperature as demonstrated by the following data:
Raising the temperature from 0o C to 35o C in isopropanol increases the rate sufficiently so reduction can be accomplished as rapidly in isopropanol at 35o C as in water at 0o C. NaBH4 reduces a wide variety of aliphatic, alicyclic, aromatic and heterocyclic ketones to their secondary alcohol. Thioketones reduced to thiols. Diketones are reduced to diols (46,47); this effect has recently been used in the synthesis of cyclophanes (48). This reduction of quinones to hydroquinones was first published in 1949 (49) and rapidly followed by similar reports (50-53). Sodium borohydride has been used in ketone reductions raging from conversion of anthraquinones to anthracenes (54), to the synthesis of codeine (54), the preparation of vitamin A esters (56), quinuclidines (57), and prostaglandins (58-60).
*For Online Consulting Only
Temperature oC 0 15 25 35
k2 x104 (L mol-1 sec-1) 15.1 36.1 63 105.0
Rohm and Haas : the Sodium Borohydride Digest
This remarkable utility is the result of the ease of handling and use of NaBH4, its selectivity for ketones and its stereospecificity. The value of selective reduction with sodium borohydride becomes obvious in compounds containing other functional groups, such as amido (61,62), epoxy (63-65), mercapto (66-67), carboxyl lactone (68), nitrile (69-70), nitro (71), ester (72-73) and many unsaturated CC bonds (74-78). This property has been utilized in the synthesis of tetracyclines (79,80) and prostaglandins (58-60, 81,82). Ketone reductions have recently been employed in the stereospecific conversion of carbonyl compounds to olefins, by NaBH4 reduction of ketophosphonamides (83) and in transposition of ketones via reduction of nitro ketones (84), e.g., cholestan-3-one to the 2-one. The recent growth in importance of aminoalcohols, resulting from the synthesis of chloramphenicol analogues and phenothiazines, is an example of the general utility of NaBH4. These are readily available by reduction of the corresponding amino ketone (85-91). The selectivity of NaBH4 is also used beneficially in converting keto acids to hydroxyacids (92-95). The sodium salt of the acid is used because the borohydrides are decomposed by organic acids. The reduction of γ− and δ- keto acids and esters leads directly to lactone formation (96-101). Normally,
*For Online Consulting Only
38
press -F for Searching
unsaturated keto acids give the unsaturated hydroxy-acids (102-104). O
O OH
NaBH4 O
Ph O
Ph
Similarly, ketoesters are reduced to the hydroxyester (105-107) and unsaturated ketoesters to unsaturated hydroxyesters (108,109). In the case of diketones, diols (110-112) or ketoalcohols (113-116) can be obtained with NaBH4, depending on the reactivity of the two carbonyl groups. Complete reduction to the diol has been employed in the synthesis of cyclophanes (117). A variety of additives or cation modifications have been employed to enhance the selectivity or reactivity of sodium borohydride in ketone reductions. Luche (118-121) has demonstrated that lanthanides promote the selective 1,2 reduction of conjugated enones to form the allylic alcohol. The use of PdCl2-NaBH4 to enhance selectivity in the reduction of oxonaphthoic acids has been reported (122). This area of chemistry has been topic of a review article. (123)
Rohm and Haas : the Sodium Borohydride Digest
Enhanced stereo- and chemoselectivity has been achieved by the use of the cations such as zinc (124-136), titanium (137- 142), zirconium (143,144), lanthanide metals (123,145), Copper (146-148) and calcium (149-156), chiral alcohols (157), chiral carboxylic acids (158-165), sugars (166-170) and macrocyclic ligands such as cyclodexstan (171-180). (Alembic 17, 21, 26, 33, 57, 53) The importance of ketone reduction with NaBH4 is shown by its innumerable applications in many fields of organic chemistry. Some of the diverse applications where the chemo- and stereoselectivity of sodium borohydride have been utilized in ketone reduction are tabulated below.
*For Online Consulting Only
39
press -F for Searching
Class of compounds Steroid ketones Amino ketones Prostaglandines Menthanones CNS suppressants Synthetic juvenile hormones Gibberellic acids Antibiotics Artificial flavors and coloring Triterpenoids Flavanoids Adamantanone Methadones Epoxy ketones Polymeric ketones Antiinflammatories Beta-Blockers Antiulcer compounds Antihypertensives Fungicides/herbicides Anti HIV Antipsychotic Anti viral Taxol
ref 181-187 85-91 58-60, 188-192 193 194- 197 198- 201 201, 202 203-210 211- 214 113, 215 216- 218 219- 221 222- 224 225 226 -228 229- 231 232- 234 235, 236 237- 239 240- 143 244- 247 248 249 250
Rohm and Haas : the Sodium Borohydride Digest
One of the most important applications of sodium borohydride is the stereospecific and selective reduction of steroid ketones. Meteos (251) has established the following sequence for the reactivity of NaBH4 for most of the ketones in the steroid molecule: ∆5-3Keto > ∆8(14)-3 keto > 3 keto A/B cis > 3 Keto A/B trans > 6 keto > 7 keto > ∆4-3 keto > 12 keto > 17 keto > 20 keto >11 keto Due to the differences in the reactivity of the keto groups in the individual positions of the steroid ring, certain keto groups can be reduced simply and selectively by using stoichiometric quantities of borohydride or by blocking individual positions. In steroid chemistry and in prostaglandin synthesis (252), it has been possible to reduce the keto group with zinc borohydride made from ZnCl2 and NaBH4 without attacking activated olefinic bonds. Recently the addition of a catalytic amount of a Co (II) complex has shown very good yields and enantiomeric excess for the synthesis of chiral alcohols from the reduction of ketones. (253- 255) The use of nonpolar solvents such as hexane are normally not considered for use with sodium borohydride reductions of ketones because of the solubility of SBH in this solvent. A unquie solution to this problem is the use of solid supports such as silica
*For Online Consulting Only
press -F for Searching
40
gel (256, 257) or alumina (258- 260) which helps to catalyze the reduction of ketones in hexanes. Luche has demonstrated that ketones can be reduced selectively in the presence of aldehydes by using NaBH4 with CeCl3 (261). References: 1) Brown, H.C.; Ichikawa, K. Tetrahedron 1957, 1, 221; Chem. Abstr. 52, 274g 2) Brown, H.C.; Bernheimer, R.; Morgan, K.J. J. Am. Chem. Soc. 1965, 87, 1280; Chem. Abstr. 62, 12996a 3) Brown, H.C.; et. al. J. Am. Chem. Soc. 1967, 89, 370; Chem. Abstr. 66, 56915f 4) Brown, H.C.; Muzzia, J. J. Am. Chem. Soc. 1966, 88, 2811; Chem. Abstr. 65, 3712h 5) Mueller, P; Perberger, J.C. Helv. Chim. Acta 1976, 59, 59, 1880; Chem. Abstr. 85, 176715f 6) Geneste, P.; Lamaty, G.; Vidal, B.C.R. Acad. Sci. Paris, Ser. C 1968, 226, 1387; Chem. Abstr. 69, 76160x 7) Sun, S.F.; Neidig, P.R. J. Org. Chem. 1969, 34, 1854; Chem. Abstr. 71, 38066e 8) Bowden, K.; Hardy, M. Tetrahedron 1966, 22, 1169; Chem. Abstr. 65, 587a 9) Warren, K.D.; Yandle, J.R. J. Chem. Soc. 1965, 5518; Chem. Abstr. 63, 17823a
Rohm and Haas : the Sodium Borohydride Digest
10) Warren, K.D.; Yandle, J.R. J. Chem. Soc. 1965, 4049; Chem. Abstr. 63, 6810a 11) Davis, R.E.; Carter, J. Tetrahedron 1966, 22, 495; Chem. Abstr. 64, 12525g 12) Wigfield, D.C.; Gowland, F.W. Tetrahedron Lett. 1976, 3373; Chem. Abstr. 86, 71391q 13) Wigfield, D.C.; Gowland, F.W. J. Org. Chem. 1976, 41, 2396; Chem. Abstr. 86, 120471bc 14) Wigfield, D.C.; Gowland, F.W. Tetrahedron Lett. 1976, 3377; Chem. Abstr. 86, 71347e 15) Wigfield, D.C.; Phelps, D.J. J. Am. Chem. Soc. 1974, 96, 543; Chem. Abstr. 80, 81887w 16) Wigfield, D.C.; Phelps, D.J. J. Org. Chem. 1976, 41, 2396; Chem. Abstr. 85, 45775c 17) Wigfield, D.C. Can. J. Chem. 1977, 55, 646; Chem. Abstr. 87, 133739r See also Wipke, W.T.; Gund, P. J. Am. Chem. Soc. 1976, 98, 8107; Chem. Abstr. 86, 4841y 18) Wigfield, D.C.; Gowland, F.W Can. J. Chem. 1978, 56, 786; Chem. Abstr. 89, 5680u 19) Rickborn, B.; Wuesthoff, M.R. J. Am. Chem. Soc. 1970, 92, 6894; Chem. Abstr. 74, 31417y 20) Wigfield, D.C.; Gowland, F.W. Tetrahedron Lett. 1979, 2209; Chem. Abstr. 92, 5827j 21) Burnet, R.D.; Kirk, D.N. J. Chem. Soc., Perkin 2 1976, 1523; Chem. Abstr. 86, 105635q
*For Online Consulting Only
press -F for Searching
41
22) Garrett, E.R.; Lyttle, D.A. J. Am. Chem. Soc. 1953, 75, 6051; Chem. Abstr. 49, 6982g 23) Brown, H.C.; Wheeler, O.H.; Ichikawa, K. Tetrahedron 1957, 1, 214; Chem. Abstr. 52, 274c 24) Wigfield, D.C.; Phelps, D.J. J. Chem. Soc, Perkin 2 1972, 680; Chem. Abstr. 76, 12619m 25) Krishnan, K.; Chandrasekaran, J. Indian J. Chem. Sec B. 1982, 21B, 595; Chem. Abstr. 98, 34038g 26) Cockerill, A.F.; Rackham, D.M. J. Chem. Soc, Perkin 2 1972, 2076; Chem. Abstr. 78, 15303k 27) Nanjappan, P.; Dhanadapani, C.; Natarajan, K.; Ramalingam, K. Indian J. Chem. Sec B 1984, 23B, 623; Chem. Abstr. 101, 229565q 28) Perberger, J.C.; Mueller, P. J. Am. Chem. Soc. 1977, 99, 6316; Chem. Abstr 87, 200601e 29) Wigfield, D.C.; Feiner, S.; Phelps, D.J. J. Org. Chem. 1975, 40, 2533; Chem. Abstr. 83, 131025y 30) Wigfield, D.C.; Phelps, D.J. Can. J. Chem. 1972, 50, 388; Chem. Abstr. 76, 112413n 31) Durand, R.; Geneste, P.; Lamaty, G.; Roque, J.P. Tetrahedron Lett. 1977, 199; Chem. Abstr 87, 5170m 32) Pasto, D.J.; Lepeska, B. J. Am. Chem. Soc. 1976, 98, 1091; Chem. Abstr. 84, 134874f 33) El-Semman, E.; Geiger, H. Justus Liebigs Ann. Chem. 1975, 75; Chem. Abstr. 82, 138943j
Rohm and Haas : the Sodium Borohydride Digest
34) Moreau, G. Bull. Soc. Chim. Fr. 1972, 2814; Chem. Abstr. 78, 15339b 35) Wigfield, D.C.; Buchanan, G.W.; Ashley, C.A.; Feiner, S. Can. J. Chem. 1976, 54, 3536; Chem. Abstr. 86, 105786q 36) Boyer, B.; Lamaty, G.; Roque, J.P.; Geneste, P. Recl. Trav. Chim. Pays-Bas 1974, 93, 260; Chem. Abstr. 86, 105786q 37) Brown, H.C.; Ichikawa, K. J. Am. Chem. Soc. 1961, 83, 4372; Chem. Abstr. 56, 7117c 38) Colonna, S.; Formasier, R. Synthesis 1975, 531; Chem. Abstr. 83, 178474j 39) Balcells, J.; Colonna, S.; Fornasier, R. Synthesis 1976, 266; Chem. Abstr. 85, 5305t 40) Masse, J.P.; Parayre, E.R. J. Chem. Soc., Chem. Commun. 1976, 438; Chem. Abstr. 85, 192270h 41) Doiuchi, T.; Minoura, Y. Isr. J. Chem. 1977, 15, 84; Chem., Abstr. 87, 200492v 42) Landini, D.; Maia, A.M.; Montanari, F.; Pirisi, M Gazz. Chim. Ital. 1975, 105, 863,; Chem. Abstr. 86, 120278u 43) Tundo, P. J. Chem. Soc. Chem. Commun. 1977, 641; Chem. Abstr. 88, 111115c 44) Lamaty, G.; Riviere, M.H.; Roque, J.P. Bull, Soc. Chim. Fr. 1983, 33; Chem. Abstr. 99, 21730x
*For Online Consulting Only
press -F for Searching
42
45) Jaeger, D.A.; Ward, M.D.; Martin, C.A. Tetrahedron 1984, 40, 2691; Chem. Abstr. 102, 61879q 46) Brooke, D.G.; Smith, J.C. J. Chem. Soc. 1957, 2732; Chem. Abstr. 51, 16311h 47) Kannan, R. Et. al. Indian J. Chem. 1967, 5, 84; Chem. Abstr. 67, 43380z 48) Hylton, T.; Boekelheide, V. J. Am. Chem. Soc. 1968, 90, 6887; Chem. Abstr. 70, 28706d 49) Chalkin, S.W.; Brown, W.G. J. Am. Chem. Soc. 1949, 71, 122; Chem. Abstr. 43, 2570d 50) Lindberg, B.; Paju, J. Svensk. Kem. Tidskir. 1953, 65, 9; Chem. Abstr. 47, 12133d 51) Nakanishi, K.; Kakisawa, H.; Hirata, Y. J. Am. Chem. Soc. 1955, 77, 3169; Chem. Abstr. 50, 3376b 52) Etienne, A.; Lepage, Y. Compt. Rend. 1955, 240, 1233; Chem. Abstr. 50, 5605b 53) Moriconi, E.J.; Wallenberger, F.T.; O’Connor, W.F. J. Org. Chem. 1959, 24, 86 54) Criswell, T.R.; Klanderman, B.H. J. Org. Chem. 1974, 39, 770; Chem. Abstr. 80, 108239a 55) Czech. 167,107 1977; Chem. Abstr. 87, 58532a 56) U.S.4,022,807 1977; Chem. Abstr. 87, 117976k 57) Ger. Offen. 2,650,876 1977; Chem. Abstr. 87, 152163q 58) U.S. 3,736,335 1973; Corresponds to Ger. Offen. 2,130,654 1971; Chem. Abstr. 76, 140041h
Rohm and Haas : the Sodium Borohydride Digest
59) Jpn. Kokai Tokkyo Koho 84, 134, 787 1984; Chem. Abstr. 102, 45692t 60) Eur. Pat. Appl. 171,992 1986; Chem. Abstr. 102, 12115r 61) Brutcher, F.V.; Vanderwerff, W.D. J. Org. Chem. 1958, 23, 146; Chem. Abstr. 52, 18370h 62) Soai, K.; Hasegawa, H.J. J. Chem. Soc. Perkin 1 1985, 769; Chem. Abstr. 103, 70915w 63) Woodward, R.B. et. al. J. Am. Chem. Soc. 1956, 78, 3087; Chem. Abstr. 50, 14732c 64) Jpn. Kokai Tokkyo Koho 80 36,448 1980; Chem. Abstr. 93, 186616d 65) Taniguchi, M.; Fujii, H.; Oshima, K.; Utimoto, K. Tetrahedron, 1995, 51, 679 66) Overberger, C.G.; Lebovits, A. J. Am. Chem. Soc. 1956, 77, 3675; Chem. Abstr. 50, 3282e 67) Overberger, C.G.; Lebovits, A. J. Am. Chem. Soc.1956, 78, 4792; Chem. Abstr. 51, 1896a 68) Dauben, W.G.; Hance, P.D.; Hayes, W.K. J. Am. Chem. Soc. 1955, 77, 4609; Chem. Abstr. 50, 6387a 69) Nickon, A.; Fieser, L.F. J. Am. Chem. Soc. 1952, 74, 5566; Chem. Abstr. 48, 1380I 70) Clive, D.L.J.; Beaulieu, P.L.; Set, L. J. Org. Chem. 1984, 49, 11313; Chem. Abstr. 100, 138634z 71) Hodges, R.; Raphael, R.A. J. Chem. Soc. 1960, 50; Chem. Abstr. 54, 8757b
*For Online Consulting Only
press -F for Searching
43
72) Adams, J.L.; Chen, T.M.; Metcalf, B.W. J.Org. Chem. 1985, 50, 2730; Chem. Abstr. 103, 123295c 73) Hassine, B. B.; Gorsane, M.; Pecher, J.; Martin, R.H. Bull. Soc. Chem. Belg. 1985, 94, 597; Chem. Abstr. 105, 152672v 74) Eastman, R.H.; Freeman, S.K. J. Am. Chem. Soc. 1955, 77, 6642; Chem. Abstr. 50, 3247a 75) Fornasier, R.; Lucchini, V.; Scimin, P.; Tonellato, U. J. Org. Chem. 1986, 51, 1769 76) Takahashi, T.; Miyazawa, M.; Tsuji, J. Tetrahedron. Lett. 1985, 26, 5139 77) Baluenga, J.; Fananas, J.F.; Sanz, R.; Garcia, F.; Carcia, N. Tetrahedron Lett. 1999, 40, 4735 78) Arase, A.; Hoshi, M.; Yamaki, T.; Nakanishi, H. J. Chem. Soc., Chem. Commun. 1994, 855 79) Boothe, J.H.; et. al. J. Am. Chem.Soc. 1959, 81, 1006; Chem. Abstr. 53, 14071b 80) Woordward, R.B. et. al. J. Am. Chem. Soc. 1962, 84, 3222; Chem. Abstr. 57, 12399g 81) Corey, E.J. Et. al. J. Am. Chem. Soc. 1968, 90, 3245; Chem. Abstr. 69, 33514x 82) Schneider, W.P. J. Chem. Soc., Chem. Commun. 1969, 304; Chem. Abstr. 70, 114673x 83) Corey, E.J.; Kwiatkowski, G.T. J. Am. Chem. Soc. 1968, 90, 6816; Chem. Abstr. 70, 19487f
Rohm and Haas : the Sodium Borohydride Digest
84) Hassner, A.; Larkin, J.M.; Bowd, J.E. J. Org. Chem. 1968, 33, 1733; Chem. Abstr. 69, 3074n 85) Hermann, E.C.; Kreuchunas, A. J. Am. Chem. Soc. 1952, 74, 5168; Chem. Abstr. 48, 1329h 86) Huebner, C.F.; Diassi, P.A.; Scholz, C.R. J. Org. Chem. 1953, 18, 21; Chem. Abstr. 48, 1329h 87) Jpn. Kokai Tokkai 76141,829 1976; Chem. Abstr. 87, 68415r 88) U.S. 4,192,805 1980; Chem. Abstr. 93, 46170d 89) Jpn Kokai Tokkyo Koho 86 78,754 1986; Chem. Abstr. 105, 133651w 90) Taylor, E.C.; Loux, H.M. Chem. And Ind. 1954, 1585 91) Weisenborn, F.L.; Applegate, H.E. J. Am. Chem. Soc. 1956, 78, 2021; Chem. Abstr. 50, 13969d 92) Wiltktop, B.; Patchett, A.A. J. Am. Chem. Soc. 1957, 79, 185; Chem. Abstr. 51, 6596b 93) Wagner, A.F. et. al. J. Am. Chem. Soc. 1955, 77,5140; Chem.Abstr. 50, 8456h 94) Drake, N.L. Tueminier, W.B. J. Am. Chem. Soc. 1955, 77, 1204; Chem. Abstr. 50, 1705c 95) Cava, M.P.; Van Meter, J.P. J. Org. Chem. 1969, 34, 538; Chem. Abstr. 70, 10628k 96) Bates, H.A.; Deng, P.N. J. Org. Chem. 1983, 48, 4478; Chem. Abstr. 99, 212331c
*For Online Consulting Only
press -F for Searching
44
97) Newman, M.S.; Dhawan, B. Khanna, V.K;. J. Org. Chem. 1986, 51, 1613; Chem. Abstr. 104, 206875p 98) Grieco, P.A.; Ferrino, S.; Vidari, G. J. Am. Chem. Soc. 1980, 102, 7586; Chem. Abstr. 94, 15535t 99) Lange G.L.; Lee, M. Tetrahedron Lett. 1985, 26, 6163; Chem. Abstr. 105, 60340g 100) Cordier, Et. Al. Compt. Rend. 1954, 238, 2004 101) Cordier, P.; Hathout W. Compt. Rend. 1956, 242, 2956; Chem. Abstr. 51, 286h 102) Ames, R.G.; Davey, W.J.; J. Chem. Soc. 1956, 3001; Chem. Abstr. 51, 2642b 103) Zorbach, W.W. J. Am. Chem. Soc. 1953, 75, 6344; Chem. Abstr. 49, 7580h 104) Cope, A.C.; Wood. G.W.; J. Am. Chem. Soc. 1957, 79, 3885; Chem. Abstr. 51, 17736g 105) Zang, H.C. ; Costanzo, M.J.; Maryanoff, B.E. Tetrahedron Lett. 1994, 4891 106) Minckler, L.S.; Hussey, A.S.; Baker, R.H. J. Am. Chem. Soc. 1956, 78, 1009; Chem. Abstr. 50, 12936h 107) Crombie, L.; Grittin, B.P. J. Chem. Soc. 1958, 4435; Chem. Abstr. 53, 10022d 108) Feit, P.W. Chem. Ber. 1960, 93, 116; Chem. Abstr. 54, 9872e 109) Silverman, I.R.; Daub, G.H.; Vander Jagt, D.L. J. Org. Chem. 1985, 50, 5550; Chem. Abstr. 104, 33954
Rohm and Haas : the Sodium Borohydride Digest
110) Juaristi, E.; Valle, L.; Valenzuela, B.A.; Aguilar, M.A. J. Am. Chem. Soc. 1986, 108, 2000; Chem. Abstr. 104, 149021f 111) Southwick, P.L.; Cremer, S.E.; J. Org. Chem. 1959, 24, 753; Chem. Abstr. 54, 611d 112) U.S. 3,217,718 1965; Chem. Abstr. 64, 5466c 113) Kolaczkowki, L.; Reusch, W. J. Org. Chem. 1985, 50, 4766; Chem. Abstr. 104, 6047h 114) Ishihara, M.; Tsuneya, T.; Shiota, H.; Shiga, M; Nakastu, K. J. Org. Chem. 1986, 51, 491; Chem. Abstr. 104, 87329b 115) Hylton, T.; Boekelheide, V. J. Am. Chem. Soc. 1968, 90, 6887; Chem. Abstr. 70, 28706d 116) Luche, J.L. J. Am. Chem. Soc. 1978, 100, 2226; Chem. Abstr. 88, 190173w 117) Gemal, A.L.; Luche, J.L. J. Am. Chem. Soc. 1981, 103, 5459; Chem. Abstr. 95, 13173y 118) Wender, P.A.; Holt, D.A. J. Am. Chem. Soc. 1985, 107, 7771; Chem. Abstr. 104, 69029z 119) Marchand, A.P.; LaRoe, W.D.; et.al. J.Org. Chem. 1986, 51, 1622 120) Greeves, N.; Warren, S.; Tetrahedron Lett. 1986, 27, 259; Chem. Abstr. 105, 2267702z 121) Yamaguchi, H.; Numata; Marui, T.; Arimoto, M; Takeda, H.; Yakugaku Zasshi 1975, 95, 477; Chem. Abstr. 83, 147410
*For Online Consulting Only
press -F for Searching
45
122) Molander, G.A. Chem. Rev. 1992, 92, 29 123) Zhang, H.C.; Costanzo, M.J.; Maryanoff, B.E. Tetrahedron Lett. 1994, 35, 4891 124) Helm, R.F.; Ralph, J. J. Wood Chem. Tech. 1993, 13, 593 125) Narasimhan, S.; Madhavan, S.; Prasad, K.G. Synth. Commun. 1997, 27, 385 126) Narasimhan, S.; Madhavan, S.; Balakumar, R.; Swarnalakshmi, S. Synth. Commun. 1997, 27, 391 127) Bhattacharyya, S. Organometallic 1996, 15, 1065 128) Bhattacharyya, S.; Chatterjee, A.; Williamson, J.S. Synth. Commun. 1997, 27, 4265 129) Bhattacharyya, S. Synth. Commun. 1995, 25, 2061 130) Narasimhan, S.; Madhavan, S.; Prasad, K.G. J. Org. Chem. 1995, 60, 5314 131) Kim, S.; Oh, C.H.; Ko, J.S.; Ahn, K.H.; Kim, Y.J. J. Org. Chem. 1985, 50, 1927 132) Ranu, B.C.; Jana, U.; Sarkaar, A. Synth. Commun. 1998, 28, 485 133) Narasimhan, S.; Madhavan, S.; Prasad, K.G. Synth. Commun. 1996, 26, 703 134) Ranu, B.C.; Sarkar, A.; Chakraborty, R. J. Org. Chem. 1994, 59, 4114 135) Bhattacharyya, S.; Chatterjee, A.; Duttachowdhury, S.K. J. Chem. Soc. Perkin Tran. 1 1994, 1 136) Liu, Y.; Schwartz, J. Tetrahedron 1995, 51, 4471 137) Liu, Y.; Schwartz, J. J. Org. Chem. 1994, 59, 940
Rohm and Haas : the Sodium Borohydride Digest
138) Dosa, P.; Kronish,I; McCallum, J.; Schwartz, J.; Barden, M.C. J. Org. Chem. 1996, 61, 4886 139) Bhattacharyya S. J. Org. Chem. 1995, 60, 4928 140) Bhattacharyya S. Tetrahedron Lett. 1994, 35, 2401 141) Armstrong, J.D.; Wolfe, C.N.; Keller, J.L.; Lynch, J.; Bhupathy, M.; Volante, R.P. Tetrahedron Lett. 1997, 1531 142) Itsuno, S.; Sakurai, Y.; Shimizu, K.; Ito, K. J. Chem. Soc. Perkin Trans 1 1990, 1859 143) Itsuno, S.; Sakurai, Y.; Ito, K. Synthesis 1988, 995 144) Barros, M.T.; Alves, C.M.; Santos, A.G.; Godinho, L.S.; Maycock, C.D. Tetrahedron. Lett. 1995, 36, 2321 145) Masaguer, C.F.; Bleriot, Y.; Charlwood, J.; Winchester, B.G.; Fleet, G.W.J. Tetrahedron, 1997, 55, 15147 146) Drouin, J.; Gauthier, S.; Patricola, O.; Lanteri, P.; Longeray, R. Synlett 1993, 791 147) Patel, H.V.; Vyas, K.A.; Pandey, S.P.; Fernandes, P.S. Org. Prep. Proc. Int. 1995, 27, 81 148) Rao, S.H.; Siva, P. Synth. Commun. 1994, 24, 549 149) Taniguchi, M.; Fujii, H.; Oshima, K.; Utimoto, K. Tetrahedron, 1995, 51, 679 150) Teixeira, L.H.; Barreriro, E.J.; Fraga, C.A.M. Synth. Commun. 1997, 27, 3241
*For Online Consulting Only
press -F for Searching
46
151) Narasimhan, S.; Ganeshwar, K.; Madhavan, S. Tetrahedron Lett. 1995, 36, 1141 152) Hisa, M.T.S.; Chu, F.S. Experientai 1977, 33, 1132; Chem. Abstr. 88, 5068p 153) Yoon, N.M.; Kang, J. Taehan Hwahak Hoechi 1975, 19, 360; Chem. Abstr. 84, 73602s 154) Tai C,-H.; Zhong, C.-P. K’Ohseuh T'ung Pau 1977, 22, 89; Chem. Abstr. 87, 67928y 155) Ito, Y.; Katsuki, T.; Yamaguchi, M. Tetrahedron Lett. 1984, 25, 6015; Chem. Abstr. 102, 220683q 156) Takahashi, T.; Miyazawa, M.; Tsuji, J. Tetrahedron Lett. 1985, 26, 5139; Chem. Abstr. 105, 60281p 157) Maiti, D.K.; Bhattacharya, P.K. Synth. Commun. 1998, 28, 99 158) Yamada, S.; Mori, Y.; Morimatsu, K.; Ishizu, Y.; Ozaki, Y.; Yoshioka, R.; Nakatani, T.; Seko, H. J. Org. Chem. 1996, 61, 8586 159) Yatagai, M.; Ohnuki, T. J. Chem. Soc. Perkin Trans. 1 1990, 1826 160) Bianch, G.; Achilli, F.; Gamba, A.; Vercesi, D. J. Chem. Soc. Perkin Trans 1 1988, 417 161) U.S. 4,943, 652 1990 162) U.S. 5,041,651 1991 163) U.S. 5,144,039 1992 164) U.S. 4,614,806 1986 165) U.S. 4,727,183 1988
Rohm and Haas : the Sodium Borohydride Digest
166) Sharma, L. Indian. J. Chem. 1997, 36B, 796 167) Sharma, L.; Singh, S. Indian J. Chem. 1994, 33B, 1183 168) Hirao, A.; Nakahama, S.; Mochizuki, H.; Itsuno, S.; Yamazaki, N. J. Org. Chem. 1980, 45, 4231 169) Zhdanov, V.A.; Alekseev, Y.E.; Korol, E.L.; Sudareva, T.P.; Alekseeva, V.G. Russ. J. Gen. Chem. 1993, 63, 1045 170) Morrison, J.D.; Gradbois, E.R.; Howard, S.I. J. Org. Chem. 1980, 45, 4229 171) Masuda, T.; Koida, K. Bull. Chem. Soc. Japn. 1973, 46, 2259; Chem. Abstr. 80, 120058y 172) Pierre, J.L.; Handel, H. Tetrahedron Lett. 1974, 2317; Chem. Abstr. 82, 57162b 173) Handel, H.; Pierre, J.L Tetrahedron 1975, 31, 997; Chem. Abstr. 83, 78152j 174) Handel, H.; Pierre, J.L Tetrahedron Lett. 1976, 2029; Chem. Abstr. 85, 176568k 175) Ravichandran, R.; Divakar, S. J. Mol. Catal. A. 1999, 137, 31 176) Pichumani, K.; Velusamy P.; Srinivasan, C. Tetrahedron, 1994, 45, 12979 177) Goldberg, Y.; Abele, E.; Rubina, K.; Popelis, Y; Shimanska, M. Chem. Heterocyclic Comp. 1993, 29, 1399
*For Online Consulting Only
press -F for Searching
47
178) Fornasier, R.; Lucchini, V.; Scrimm, P.; Tonellato, U. J. Org. Chem. 1986, 51, 1769 179) Sakuraba, H.; Inomata,N. Tanaka, Y. J.Org. Chem. 1989, 54, 3482 180) Fornasier, R.; Reniero, F.; Scrimm, P.; Tonellato, U. J. Org. Chem. 1985, 50, 3209 181) Garrett, E.R.; Lyttle, D.A. J. Am. Chem. Soc. 1953, 75, 6051; Chem. Abstr. 49, 6982g 182) Dauben, W.G.; Blanz, E.J.; Jui, J. J. Am. Chem. Soc. 1953, 75, 6051, chem. Abstr. 51, 1223I 183) Wheeler, O.H.; Mateos, J.L. Can. J. Chem. 1958, 36, 1049; Chem. Abstr. 53, 2283g 184) Wheeler, O.H.; Mateos, J.L. Can. J. Chem. 1958, 36, 1431; Chem. Abstr. 53, 7241b 185) Hajos, A.; Fuchs, O. Acta, Chim. Acad. Sci. Hung. 1959, 21, 137; Chem. Abstr.54, 19764a 186) Takahashi, T.; Yamada, H.; Tsuji, J.; J. Am. Chem. Soc. 1981, 103, 5259; Chem. Abstr. 95, 169594u 187) Jpn. Kokai Tokkoyo Koho 82, 116,096, 1982; Chem. Abstr. 98, 16938w 188) Bagli, J.F.; Bogri, T. J. Org. Chem. 1972, 37, 2132; Chem. Abstr. 77, 74851q 189) Bundy, G.L.; Danials, E.G.; Lincoln, F.H.; Pike, J.E. J. Am. Chem. Soc. 1972, 9, 1223; Chem. Abstr. 76, 124429k
Rohm and Haas : the Sodium Borohydride Digest
190) Mirjang, M.; Dorn, C.R. J. Org. Chem. 1972, 37, 1818; Chem. Abstr. 77, 34022p 191) Barros, M. T.; Alves, C.M.; Santos, A.G.; Godinho, L.S.; Maycok, C.D. Tetrahedron Lett. 1995, 36, 2321; Chem. Abstr. 123 9179 192) U.S. 4,739,078 1988 193) Tadwalker, V.R.; Narayanaswamy, M.; Rao, A.S. Inidian J. Chem. 1972, 9, 1223; Chem. Abstr. 76, 85932x 193) Daum, S.J.; Martini, C.M.; Kullnig, R.K.; Clarke, R.L. J. Org. Chem. 1972, 37, 1665; Chem. Abstr. 77, 34736z 194) Belg. 901, 127 1985; Chem. Abstr. 103, 71329v 195) Eur. Pat. Appl. 138, 716 1985; Chem. Abstr. 103, 32295m 196) Avramova, P.; Ilarionov, T.; Dryanovska, L. Pharmazie 1985, 40, 579; Chem. Abstr. 105, 133629k 197) Loew, P.; Johnson, W.S. J. Am. Chem. Soc. 1971, 93, 3766; Chem. Abstr. 75, 88398t 198) Faulkner, D.J.; Perterson, M.R. J. Am. Chem. Soc. 1971, 93, 3766; Chem. Abstr. 75, 88397s 199) Czech. 195,530 1982; Chem. Abstr. 98, 88962x 200) Chojecka-Koryn, E.; Sobotka, W. Pol. J. Chem. 1981, 55, 1241; Chem. Abstr. 99, 38656a
*For Online Consulting Only
press -F for Searching
48
201) Corey, E.J.; Carney, R.L. J. Am. Chem. Soc. 1971, 93, 7318; Chem. Abstr. 76, 46327j 202) Ger (east) 156,707 1982; Chem. Abstr. 99, 5878w 203) Barton, D.H.; Halpern, B.; Porter, Q.N.; Collins, D.J. J. Chem. Soc (C), 1971, 2166; Chem. Abstr. 75, 48755a 204) Yoshimoto, A.; Matsuzawa, Y. et. al. J. Antibiot. 1984, 37, 920; Chcem. Abstr. 101, 192369a 205) Iida, H.; Yamazaki, N.; Kibayashi, C. J. Org. Chem. 1986, 51, 1069; Chem. Abstr. 104, 168240t 206) U.S. 4,465,674 1984; Chem. Abstr. 101, 230951u 207) Ulibarri, G.; Nadler, W.; Skrydstrup, T.; Audrain, H.; Chiaroni, A.; Riche, C.; Grierson, D.S. J Org. Chem. 1995, 60, 2753; Chem. Abstr. 124 30187 208) U.S. 5,869,449 1999 209) U.S. 5,648,456 1997 210) U.S. 5,869,449 1999 211) Ger. Offen. 2,035,901 1971; Chem. Abstr. 75, 35259s 212) U.S. 3,558,712 1971; Chem. Abstr. 74, 100242b 213) U.S. 4,269,862 1981; Chem.Abstr. 95, 95775e 214) Jpn. Kokai Tokkyo Koho 82 28,079 1982; Chem. Abstr. 96, 218067f 215) Nasipuri, D.; Mukherjee, P.R.; Pakrashi, C.S.; Datta, S.; Ghosh-Dastidar, P.P. J. Chem. Soc. Perkin 1 1976, 321; Chem. Abstr. 84, 105838s 216) Grouiller, A.; Pacheco, H.C. R. Acad. Sci., Ser. C 1971, 272, 2085; Chem. Abstr 75, 75584a
Rohm and Haas : the Sodium Borohydride Digest
217) Stafford, H.A.; Lester, H.H. Plant Physiol. 1985, 78, 791; Chem. Abstr. 103, 157434n 218) Takahashi, H.; Kubota, Y.; Iguchi, M.; Onda, M. Chem. Pharm. Bull. 1985, 33, 3134; Chem. Abstr. 105, 226273q 219) Murray, R.K.; Babiak, K.A.; Morgan, T.K. J. Org. Chem. 1975, 40, 2463; Chem. Abstr. 83, 131183y 220) Subramaniam, R.; Fort, R.C. J. Org. Chem. 1984, 49, 2891; Chem. Abstr. 101, 71942y 221) Cheung, C.K.; Tseng, L.T.; Lin, M.H.; Srivastava, S.; Lenoble, W. J. J. Am. Chem. Soc. 1986, 108, 1598; Chem. Abstr. 104, 14801r 222) Haller, R.; Ruemmler, R. Arch. Pharm. 1973, 306, 510; Chem. Abstr. 79, 125679r 223) Haller, R.; Ruemmler, R. Arch. Pharm. 1973, 306, 408; Chem. Abstr. 79, 77938a 224) Haller, R.; Ruemmler, R. Arch. Pharm. 1973, 306, 431; Chem. Abstr. 79, 77917t 225) Weissenberg, M. J. Chem. Soc. Perkin 1 1978, 568; Chem. Abstr. 89, 147130p 226) Merle-Aubry, L.; Merele, Y. Selegny, E. Macromol. Chem. 1973, 172, 115; Chem. Abstr. 80, 60366k 227) Pieta, P.G.; Cavallo, P.F.; Takahashi, K.; Marchall, G.R. J. Org. Chem. 1974, 39, 44; Chem. Abstr. 80, 96353t
*For Online Consulting Only
press -F for Searching
49
228) Orlowski, R.C.; Walter, R.; Winkler, D. J. Org. Chem. 1976, 41, 3701; Chem. Abstr. 85, 177951s 229) PCT int. appl. 83, 02,613 1983; Chem. Abstr. 99, 175755w 230) Ger. Offen. 3,440,503 1985; Chem. Abstr. 104, 129660k 231) Eur. Pat. Appl. 189, 142 1986; Chem. Abstr. 105, 190651v 232) Willard, A. K.; Smith, R.L.; Cragoe, E.J. J. Org. Chem. 1981, 46, 3846; Chem. Abstr. 96, 52244j 233) U.S. 4,558,129 1985; Chem. Abstr. 104, 186449x 234) U.S. 4,330,554 1982; Chem. Abstr. 97, 144756b 235) Aristoff, P.A.; Johnson, P.D.; Harrison, A.W. J. Am. Chem. Soc. 1985, 107, 7967; Chem. Abstr. 104, 68650h 236) U.S. 4,304,790 1981; Chem. Abstr. 96, 142440z 237) U.S. 4,474,778 1984; Chem. Abstr. 102, 78746s 238) Eur. Pat. Appl. 145,494 1985; Chem. Abstr. 104, 68892p 239) Can. 1,208,647 1986; Chem. Abstr 105, 208894p 240) U.S.; 4,486218 1984; Chem. Abstr. 103, 22594u 241) Jpn. Kokai Tokkyo Koho 84, 122,469 1984; Chem. Abstr. 102, 62090n 242) U.S. 4,547,582 1985; Chem. Abstr. 104, 148534p 243) U.S. 5,489,697 1996 244) U.S. 5,869,324 1999 245) U.S. 5,847,164 1998 246) U.S. 8,874,591 1999 247) U.S. 5,658,916 1997
Rohm and Haas : the Sodium Borohydride Digest
248) U.S. 5,476,931 1995 249) U.S. 5,856,532 1999 250) Mateos, J.L. J. Org. Chem. 1959, 24, 2034; Chem. Abstr. 54, 12199d 251) Corey, E.J.; Albonico, S.M.; Koelliker, U.; Schaaf, T.K.; Varma, R. K. J. Am. Chem. Soc. 1971, 93, 1491; Chem. Abstr. 74, 141053j 253) Nagata, T.; Sugi, K.D.: Yamamda, T.; Mukaiyama, T. Synlett. 1996, 1076 254) Sugi, K.D.; Nagata, T.; Yamamda, T.; Mukaiyama, T. Chem. Lett. 1996, 737 255) T. Mukaiyama, T. Nagata, K. Yorozu, T. Yamada Angew. Chem. Int. Ed. Engl., 1995, 34, 2145 256) Ranu, B.C.; Das, A.R. J. Org. Chem. 1991, 56, 4796 257) Yakabe, S.; Hirano, M.; Morimoto, T. Synth. Commun. 1999, 29, 295 258) Yakabe, S.; Hirano, M.; Morimoto, T. Can J. Chem. 1998, 76, 1916 259) Yakabe, S.; Hirno, M.; Clark, J.H.; Morimoto, T. J. Chem. Research (S) 1998, 322 260) Varma, R.S.; Saini, R.K. Tetrahedron Lett. 1997, 38, 4337 261) Luche, J.L.; Germal, A.L. J. Am. Chem. Soc. 1979, 79, 5848
*For Online Consulting Only
press -F for Searching
50
Rohm and Haas : the Sodium Borohydride Digest
CARBOXYLIC ACIDS Alembic: 48, 49, 55, 61, 62 Carboxylic acids are not normally reduced with sodium borohydride in protic solvents. However, there are a few techniques that permit the direct borohydride reduction of carboxylic acids or their easily prepared derivatives. A number of aromatic and aliphatic carboxylic acids (and esters) have been reduced to their corresponding alcohol using sodium borohydride at high temperatures (300o C) in the presence or absence of any solvent (1,2). C5H11COOH + NaBH4 Æ C6H13OH Using a 0.25 mole equivalent of borohydride to acid, the hexyl caproate was obtained. Enol esters derived from the reaction of carboxylic acids with N-ethyl-5-phenylisoxazolium-3’sulfoxate can be reduced with sodium borohydride in water to the alcohols (3). A series of perfluorinated acids were reduced to the alcohols with NaBH4 (4):
*For Online Consulting Only
51
press -F for Searching O
OH NaBH4
O
H H
O
OH CF3
CF3
Carboxylic acids can be reacted with ethyl chloroformate to form the mixed anhydrides, in situ, which are then reduced in aqueous tetrahydrofuran to the corresponding alcohols (5). R O R
+ OH Cl
O
O NaBH4 OEt
O O
OH R
H
H
EtO
Other reagents such as cyanuric chloride, tosyl chloride and BOP (6, 7, 8) have reduced amino acids to their corresponding chiral alcohol in high yield. This technique is very cost effective as well as very mild. One problem with this methodology is that all carboxylic acid and alcohol groups will react with these reagents. Therefore all hydroxy group that are not to be reduced must be protected prier to treatment. This technique has been applied in a number of syntheses of complex materials (9- 13) The reductive system of NaBH4/metal chloride/diglyme is effective for reducing carboxylic acids.
Rohm and Haas : the Sodium Borohydride Digest
AlCl3 has been used successfully, but will also reduce other functional groups if they are present (14,15). Zinc borohydride will reduce both aliphatic and aromatic carboxylic acids under reflux conditions in THF in high yields, amino acids have also been reduced to chiral amino alcohols with this methodology. (16,17) Cuprous halide/NaBH4/diglyme gives a reducing system which is specific for carboxylic acids while TeCl4 or ThCl4 renders it specific for reduction of esters and acids (18). Zirconium tetrachloride with sodium borohydride will also reduce carboxylic acids to their corresponding alcohols. (19) NaBH4 has been used with TiCl4 to reduce both a carboxylic acid to the alcohol and a nitro group to the amine, in a single step, during the synthesis of the alkaloid ismine (20). Ti(OiPr)3 with Sodium borohydride also reduces aliphatic and aromatic carboxylic acids as well as amino acids to their corresponding alcohol in high yields. (21) Reagents such as I2, Me3SiCl, BF3, MeSO2OH and H2SO4 are combined with borohydrides to form borane, which is a very active component for the reduction of carboxylic acids.(22-28) These combinations of reagents have reduced both aliphatic and aromatic carboxylic acid as well as amino acids to their corresponding alcohols.
*For Online Consulting Only
press -F for Searching
52
Thioacids are also rapidly reduced to high yields of the thiol, with small amounts of alcohols, by the system AlCl3/NaBH4/diglyme (29). Sodium borohydride alone normally does not reduce carboxylic acid but the addition of triphenylborate reduces both aromatic and aliphatic acids.(30) Other reagents which can be used are dimethyl sulfate (31). The addition of trifluoro acetic acid and catechol to sodium borohydride in THF at room temperature will reduce both aliphatic and aromatic carboxylic acids. (32) The combination of Amberlist-15, LiCl and sodium borohydride in methanol will reduce amino acids in high yields. (33) Borohydride exchange resins with chloroformate have reduced both aliphatic and aromatic carboxylic groups at RT. (34) References: 1) Nose, A.; Kudo, T. Yakugaku Zasshi 1976, 96, 1401; Chem. Abstr. 86, 139533y 2) Yang, C.; Pittman, C.U. Synthetic Commun. 1998, 28, 2027 3) Hall, P.L.; Perfeti, R.B. J. Org. Chem. 1974, 39, 11; Chem. Abstr. 80, 96354 4) U.S. 3,752,847 1973; Chem.Abstr. 79, 91611v 5) Ishizumi, K.; Koga, K.; Yamada, S. Chem. Pharm. Bull. 1968, 16, 492; Chem. Abstr. 69, 58805g
Rohm and Haas : the Sodium Borohydride Digest
6) Faloprni, M; Porcheddu, A.; Taddei, M. Tettrahedron Lett. 1999, 40, 4395 7) Kokotos, G.; Noula, C. J. Org. Chem. 1996, 6994 8) McGreary, R.P. Tetrahedron Lett. 1998, 39, 3319 9) Ger. Offen. ,007,366 1981; Chem. Abstr. 95, 2033633t 10) Jpn. Tokkoyo Koho 83 33,866 1983; Chem. Abstr. 100, 68730b 11) Olsen, R.K.; Ramasamy, K.; Emery, T J. Org. Chem. 1984, 49, 3527; Chem. Abstr. 101, 131063z 12) Jpn. Kokai Tokkyo Koho 85, 174,769 1985; Chem. Abstr. 104, 88456c 13) U.S. 4,760,196 1988 14) Brown, H.C.; Subba Rao, B.C. J. Am. Chem. Soc. 1955, 77, 3164; Chem. Abstr. 50, 3995c 15) Blawood, R.K.; Hess, G.B.; Larrabee, C.E.; Pilgrim, F.J. J. Am. Chem. Soc. 1958, 80, 6244; Chem. Abstr. 53, 11373e 16) Narasimhan, S.; Madhavan, S.; Prasad, K.G. J. Org. Chem. 1995, 60, 5314 17) Narasimhan, S.; Madhavan, S.; Prasad, K.G. Synth. Commun. 1996, 26, 703 18) Subba Rao, B.C.; Thakar, G.P. J. Sci. Indust. Res. 1961, 20b, 317 19) Itsuno, S.; Sukurai, Y.; Ito, K. Synthesis 1988, 995
*For Online Consulting Only
press -F for Searching
53
20) Prabhakar, S.; Lobo, AM.; Marques, M.M.; Tavares, M.R. J Chem. Research (s) 1985, 394; Chem. Abstr. 104, 225068u 21) Ravikumar, K.S.; Chanderasekaran, S. J. Org. Chem. 1996, 61, 826 22) Prasa, A.S.B.; Kanth, J.V.b.; Periasamy, M. Tetrahedron 1992, 48, 4623 23) Giannis, A.; Sandoff, K. Angew. Chem. Int. Ed. Engl. 1989, 28, 218 24) Sengupta, S.; Sahu, D.P.; Chatterjee, S.K. Indian J. Chem. 1994, 33b, 285 25) Wann, S.R.; Thorsen, P.T.; Kreevoy, M.M. J. Org. Chem. 1981, 46, 2579 26) Boesten, W.H.; Schepers, C.H.M.; Roberts, M.J.A. EPO 322982 A2 1989 27) Abiko, A.; Masamiune, S. Tetrahedron Lett. 1992, 33, 5517 28) U.S. 5,744,611 1998 29) Heasly, G.E. J. Org. Chem. 1971, 36, 3235; Chem. Abstr. 13524f 30) Yoon, N.M.; Chho, B.T.; Yoo, J.U.; Kim, G.P.. J. Korean Chem. Soc. 1983, 27, 434 31) Cho, B.T.; Yoon, N.M. Bull. Korean Chem. Soc. 1982, 3, 149 32) Suseele, Y.; Periasamy, M. Tetrahedron 1992, 42, 371 33) Anand, R.C.; Vimal Tetrahedron Lett. 1998, 39, 917
Rohm and Haas : the Sodium Borohydride Digest
34) Bandger, B.P.; Modhave, R.K.; Wadgaonkar, P.P.; Sande, A.R. J. Chem. Soc., Perkin Trans 1 1996, 1993
*For Online Consulting Only
press -F for Searching
54
Rohm and Haas : the Sodium Borohydride Digest
AMIDES Alembic: 9, 47, 50, 61, 62 Amides were once considered to be not reducible by NaBH4. Attempts to reduce primary amides in boiling diglyme led to the formation of nitriles with the elimination of water (1). In refluxing pyridine, primary amides form the nitrile, secondary amides do not react and tertiary amides are slowly reduced to amine (2,3). When catalyzed by salts of transition metals, such as cobalt, nickel and zirconium, NaBH4 has been shown to reduce primary and secondary amides to the amine. (4, 5) Zn(BH4)2 can reduce both aromatic and aliphatic amides to amines in high yields in refluxing THF. (6) A cobalt complex recently developed will reduce amides using NaBH4 as the hydride source (7) A number of useful techniques to accomplish amides reductions are now known. These include reduction with TiCl4/NaBH4 (8,9) reduction with Bu4NBH4 in dichloromethane (10), reduction with NaBH4 via imino derivatives using POCl3 (11), and reduction via thioamides and (alkylthio) methyleniminium salts (12). The asymmetric reduction of pyruvamides has also been reported
*For Online Consulting Only
press -F for Searching
55
(13), using NaBH4 in conjunction with chiral amines. 1o, 2o and 3o aromatic and aliphatic amides are reduced using a combination of NaBH4 with reagents such as I2, Me3SiCl, BF3, MeSO2OH and R2SeBr2 at RT. (14, 15, 16, 17, 18) These combination of reagents form borane in-situ which is the ingredient which reduce the amide group. B(OPh)3 is another reagent that is used catalytically with NaBH4 to reduce amides in high yields.(19) The reduction of amides with NaBH4 in ether solvents is accomplished by the addition of 1 molar equivalent (based on NaBH4) of glacial acetic acid to the stirred amide-NaBH4-solvent mixture. For the preparation of tertiary amines from disubstituted amides, trifluoroacetic is substituted for acetic acid (20,21). A very similar technique where DMSO was the solvent gave good yields of a wide variety of primary, secondary and tertiary amines (22). The activation of NaBH4 with ethanedithiol or benzenethiol in boiling THF permitted the reduction of certain amides and imides to the corresponding amines (23). It has recently been shown that cyclic secondary amides can be selectively reduced to an alcohol in the presence of tertiary amide by chemically activating the secondary amine with BOC or Cbz. (24)
Rohm and Haas : the Sodium Borohydride Digest
References: 1) Elzey, S.E. Jr.; Mack, C.H.; Connick, W.J. Jr. J. Org. Chem. 1967, 32, 846; Chem. Abstr. 67, 2860n 2) Kikugawa, Y.; Ikegami, S.; Yamada, S. Chem. Pharm. Bull 1969, 17, 98; Chem. Abstr. 70, 97491 3) Saito, I.; Kiugawa, Y.; Yamada, S. Chem. Pharm. Bull. 1970, 18, 1731; Chem. Abstr. 73, 110093x 4) Satoh, T.; Suzuki, S.; Suzuki, Y.; Miyaji, Y.; Imai, Z. Tetrahedron Lett. 1969, 4555; Chem. Abstr.94, 1499e 5) Itsuno, S.; Sukurai, Y.; Ito, K. Synthesis 1988, 995 6) Narasimhan, S.; Madhavan, S.; Balakumar, R.; Swarnalakshmi, S. Synth. Commun. 1997, 27, 391 7) Yamada, T.; Ohtsauka, Y.; Ikeno, T. Chem. Lett. 1998, 1129 8) Kano, S.; Tanaka, Y.; Sugino, E.; Hibino, S. Synthesis 1980, 695; Chem. Abstr. 94, 14599e 9) Jp. Okai Tokkyo Koho 80, 162, 756 1980; Chem. Abstr. 95, 62023e 10) Wakamatu, T.; Inaki, H.; Ogawa, A.; Watanabe, M. Ban, Y. Heterocycles 1980, 14, 1437; Chem. Abstr. 94, 3027a 11) Kuehne, M.E. Shannon, P.J. J. Org. Chem. 1977, 42, 2082; Chem. Abstr. 87, 22928g 12) Raucher, S.; Klein, P. Tetrahedron Lett. 1980, 21, 4061; Chem. Abstr. 94, 156223b
*For Online Consulting Only
press -F for Searching
56
13) Munegumi, T.; Harada, K. Bull Chem. Soc. Jpn. 1983, 56, 298; Chem. Abstr. 99, 53287z 14) Prasa, A.S.B.; Kanth, J.V.b.; Periasamy, M. Tetrahedron, 1992, 48, 4623 15) Giannis, A.; Sandoff, K. Angew. Chem. Int. Ed. Engl. 1989, 28, 218 16) Sengupta, S.; Sahu, D.P.; Chatterjee, S.K. Indian J. Chem. 1994, 33b, 285 17) Wann, S.R.; Thorsen, P.T.; Kreevoy, M.M. J. Org. Chem. 1981, 46, 2579 18) Akabori, S.; Takanohashi, Y. J. Chem. Soc.; Perkin Trans 1, 1991, 479 19) Yoon, N.M.; Chho, B.T.; Yoo, J.U.; Kim, G.P.. J. Korean Chem. Soc. 1983, 27, 434 20) Umino, N.; Iwakuma, T.; Itoh, N. Tetrahedron Lett. 1976, 763; Chem. Abstr. 85, 20719z 21) Malawska, B.; Gorczyca, M. Pol. J. Chem. 1985, 59, 811; Chem. Abstr. 105, 226250e 22) Thorsen, P.T.; Kreevoy, M.M. J. Org. Chem. 1981, 46, 2579; Chem. Abstr. 95, 5881j 23) Maki, Y.; Kikuchi, K.; Sugiyama, H.; Seto, S. Chem. Ind. 1976, 322; Chem. Abstr. 85, 62767u 24) Lee, B.H.; Clothier M.F. Tetrahedron Lett. 1999, 40, 643
Rohm and Haas : the Sodium Borohydride Digest
ACID ANHYDRIDES Alembic: 50 Because of their chemical nature, acid anhydrides cannot be reduced by borohydride in aqueous solvents. Early literature reports only a few instances of carboxylic anhydrides reductions with NaBH4 in ether solvents, The products being either lactones (1-4), diols (5), or alcohols (6). Cyclic anhydrides are readily reduced by NaBH4 to γ and δ-lactones in very good yields (713) to form antibiotics, (14) growth factors (15) and β-amino acids (16,17) . Additional reports of the use of NaBH4 for reducing anhydrides have appeared in the literature (18- 21) Mixed carboxylic-diphenylphosphoric acid and diphenylphosphorochloridate in the presence of triethylamine, were reduced with excess NaBH4 to the corresponding primary alcohols in fair yield. Nitro, ester, amides groups and conjugated double bonds were not affected (22). The NaBH4/TiCl4 (4:1) system in diglyme has been reported to reduce acid anhydrides to diols (23).
*For Online Consulting Only
press -F for Searching
57
The reduction of a series of substituted phthalic anhydrides to phthalides with sodium borohydride has been reported (24). Preferential reduction of the carbonyl function adjacent to the 3- substituent was observed. In the 4- substituted analogous, selectivity of reduction was found only when, the substituent is electron donating. Acid anhydrides formed from amino acids and isobutyl chloroformate are reducible with sodium borohydride to form chiral amino alcohols in high yields. (25,26) References: 1) Vaughn, W.R.; Goetschel, C.T.; Goodow, M.H.; Warren, C.L. J. Am. Chem. Soc. 1963, 85, 2282; Chem. Abstr. 59, 6443c 2) Cross, B.E.; Galt, R.H.B.; Hanson, J.R. J. Chem. Soc. 1963, 5052; Chem. Abstr. 60, 566f 3) Birckelbaw, M.E.; LeQuesne, P.W.; Wocholski, C.K. J. Org. Chem. 1970, 35, 588; Chem. Abstr. 72, 100989j 4) Longlois, N.; Gastambide, B. C. Acad. Sci. Paris, Ser, C 1967, 264, 1878; Chem. Abstr. 67, 90956b 5) Longlois, N.; Gastambide, B. C. Helv. Chim. Acta 1968, 51. 2048; Chem. Abstr. 70, 29097t 6) Perron, Y.G. et. al. J. Med. Chem. 1964, 7, 483; Chem. Abstr. 61, 5631a 7) Bailey, D.M.; Johnson, R.E. J. Org. Chem. 1970, 35, 3574; Chem. Abstr. 73, 120261q
Rohm and Haas : the Sodium Borohydride Digest
8) Jefford, C.W.; Wang, J. Tetrahedron Lett. 1993, 34, 1111 9) Jefford, C.W.; Wang, J.B.; Lu, Z.H. Tetrahedron Lett. 1993, 34, 7557 10) Patterson, J.W. J. Org. Chem. 1995, 60, 560 11) Kinoshita, Y.; Watanabe, H.; Kitahara, T.; Mori, K. Synlett. 1995, 186 12) Patterson, J.W. J. Org. Chem. 1995, 60, 560 13) Miki, Y.; Hachiken, H. Synlett 1993, 333 14) Roa, A.V.R.; Reddy, D.R.; Annapurna, G.S.; Deshpande, V.H. Tetrahedron Lett. 1987, 28, 451 15) Roa, A.V.R.; Reddy, R.G. Tetrahedron Lett. 1992, 33, 4061 16) Jefford, C.W.; Wang, J. Tetrahedron Lett. 1993, 34, 1111 17) Jefford, C.W.; Wang, J.B.; Lu, Z.H. Tetrahedron Lett. 1993, 34, 7557 18) Brooks, C.J.W.; Ekhato, I.V. J. Chem. Soc., Chem. Commun. 1982, 943; Chem. Abstr. 98, 34839u 19) U.S. 4,473,700 1984; Chem. Abstr. 102, 9487w 20) Jpn. Kokai Tokkyo Koho 85,156,691 1985; Chem. Abstr. 104, 207262y 21) Zhidkova, T.A. et. al. Khim. 1985, 21, 1653; Chem. Abstr. 105, 43108v
*For Online Consulting Only
press -F for Searching
58
22) Koizumi, T.; Yamamoto, N.; Yoshii, E. Chem. Pharm. Bull. 1973, 21, 312; Chem. Abstr. 78, 135830b 23) Subba Roa, B.C. Curr. Sci. 1961, 30, 218; Chem. Abstr. 56, 3326c 24) McAlees, A.J.; Mc Crindle, R.; Sneddon, D. J. Chem. Soc., Perkin Trans 1 1977, 2038; Chem. Abstr. 88, 50432e 25) Rodriques, M.; Llinares, M.; Doulut, S. Heitz, A.; Martinez, J. Tetrahedron Lett. 1991, 32, 923 26) Ho, M.; Chung, J.K.K.; Tang, N. Tetrahedron Lett. 1993, 34, 6513
59
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest
ACID HALIDES
Cl
Alembic: 50, 58
O NaBH4
N
NaBH4 reduction of acids chlorides in inert solvents (generally ethers) is a generally accepted synthetic procedure (1-6). NaBH4 reduction of various acid chlorides from hydantoic peptides has been report (7). R
O
N
O
NaBH4
O H
N
Cl
HO
O
N H
O
OEt
O
O
O
This reduction has been applied to synthesis of oxazoles having anti-inflammatory activity (8). O
Cl O
N Ar
Cl
NaBH4
O
N Ar
H
H
O
The following acid chloride reductions have been reported:
*For Online Consulting Only
OH Cl NaBH4
(OC)3Fe
OH
(10)
OEt
H
H
H H
NaBH4
OH H
(9)
O
Cl
O
OH N
H
N
O
R
H
H
H
(OC)3Fe OH
H H H
(11)
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest O
O NaBH4
(12) HO
HO
Cl O
HO
H H
The reduction of acid chlorides with tetrabutylammonium borohydride in dichloromethane provides instantaneous reactions and nearly quantitative yields (13). Similar reactions of quaternary borohydrides in binary solvents or the use of NaBH4 with a phase transfer catalyst, have been reported (14). Phosphonium borohydride can reduce acid chlorides to alcohols in high yields in aprotic solvents at RT. (15) The Luche method, using CeCl3 with NaBH4, has been applied to the reduction of conjugated unsaturated acid chlorides to the corresponding unsaturated alcohol (16). NaBH4 reduces acid chlorides to aldehydes in good yield in the presence of cadmium chloride and DMF (17,18). The reagent bis-(triphenylphosphine) copper (1) borohydride, easily prepared from NaBH4, also gives high yields of aldehydes from acid chlorides (19-22). Reduction to aldehydes by NaBH4 without added metal salts has been studied (23). Careful control of the ratio of NaBH4 to acid chloride, operation at – *For Online Consulting Only
60
70oC in dimethylformamide-tetrahydrofuran solvent and strict attention to the method of quenching the reaction minimized overreduction to the alcohol. Aromatic and aliphatic acid chlorides are reduced to alcohols with SBH in MeOH.(24) Acid chlorides can be reduced to aldehydes with SBH in the presence of pyridine as a borane scavenger to stop over reduction to the alcohol. (25) Zinc borohydride can reduce acid chlorides to their corresponding alcohols in high yield in ether type solvents. (26,27) The addition of organic nitrogen containing bases such as DABCO and pyrazine have been added to zinc borohydride to reduce acid chlorides to alcohols (28,29) The addition of titanium tetraisopropoxide to NaBH4 has been shown to reduce acid chlorides to alcohols in 5 to 10 mins. (30) Cyanoborohydride has also been shown to reduce acid chloride to alcohols in high yields. (31) References: 1) Chaikin, S.W.; Brown, W.G. J. Am. Chem. Soc. 1949, 71, 122; Chem. Abstr. 43, 2570d 2) Walton, E. Et. Al. J. Am. Chem. Soc. 1955, 77, 5144; Chem. Abst. 50, 8452h 3) Tomita, M; Hirai, K. J. Pharm. Soc. Japan. 1958, 78, 798; Chem. Abstr. 52, 1875g 4) Vecchi, A.; Melone, G. J. Org. Chem. 1959, 24, 109; Chem. Abstr. 54, 6627f
Rohm and Haas : the Sodium Borohydride Digest
5) Endres, G.F.; Epstein, J. J. Org. Chem. 1959, 24, 1497; Chem. Abstr. 54, 4379h 6) Sato, S.; Ono, Y.; Tatsumi, S.; Wakamatsu, H.; Nippon Kagaku Zasshi 1971, 92, 178; Chem. Abstra. 76, 33755x 7) Wessey, F. Schloegl, K.; Korger, G. Nature 1952, 169, 708; Chem. Abstr. 47, 2700f 8) Brit. 1,139,940 1969; Chem. Abstr. 70, 106494z 9) Ger, Offen. 2,237,832 1973; Chem. Abstr. 78, 111342t 10) Hudrilik, P.F.; Rudnik, L.R.; Korzenowski, S.H. J. Am. Chem. Soc. 1973, 95, 6848; Chem. Abstr. 80, 3149t 11) Berens, G. et. al. J. Am. Chem. Soc. 1975, 97, 7076; Chem. Abstr. 83, 206405h 12) Paul, K.G.; Johnson, F.; Favara, D.; J. Am. Chem. Soc. 1976, 41, 690; Chem. Abstr. 84, 135153g 13) Raber, D.J. Guida, W.C. J. Org. Chem. 1976, 41, 690; Chem. Abstr. 84, 88901n 14) Brit. Pat. Appl 2,1544 1985; Chem. Abstr. 104, 168107e 15) Firouazbadi, H.; Adibi, M. Synth. Commun. 1996, 26, 2429 16) Lakshmy, K.V.; Mehta, P.G.; Seth, J.P.; Trivedi, G.K. Org. Prep. Proced. Int. 1985, 17, 251; Chem Abstr. 104, 88199w
*For Online Consulting Only
press -F for Searching
61
17) Johnstone, R.A.W.; Telford, R. J. Chem. Soc., Chem. Commun. 1978, 354; Chem. Abstr. 89, 16547t 18) U.S. 4,211,727 1980; Chem. Abstr. 93, 203401b 19) Fleet, G.W.; Fller, C.J. Harding, P.J.C. Tetrahedron Lett. 1978, 1437; Chem Abstr. 89, 108495s 20) Barlett, P.A.; Johnson, C.R. J. Am. Chem. Soc. 1985, 107, 7792; Chem. Abstr. 104, 50753j 21) Sorrell, T.N.; Pearlman, P.S. J. Org. Chem. 1980, 45, 3449 22) Paquette, LA.; Teleha, C.A.; Taylor, R.T.; Maynard, G.D.; Rogers, R.D.; Gallucci, J.C.; Springer, J.P. J. am. Chem. Soc. 1990, 112, 265 23) 23)Babler, J.H.; Invergo, B.J. Tetrahedron Lett. 1981, 21, 11; Chem. Abstr. 94, 174230f 24) Kang, S.K.; Lee., D.H. Bull. Korean Chem. Soc. 1988, 9, 402 25) Babler, J.H. Synth. Commun. 1982, 12, 839 26) Kim, S.; Oh, C.H.; Ko, J.S.; Ahn, K.H.; Kim, Y.J. J. Org. Chem. 1985, 50, 1927 27) Kotsuki, H.; Ushio, Y.; Yoshimura, N.; Ochi, M. Bull. Chem. Soc. Jpn. 1988, 61, 2684 28) Firouzabadi, H.; Zeynizadeh, B. Bull. Chem. Soc. Jpn. 1997, 70, 155 29) Tamami, B.; Lakouraj, M.M. Synth. Commun. 1995, 25, 3089
Rohm and Haas : the Sodium Borohydride Digest
30) Ravikumar, K.S.; Chanderasekaran, S. J. Org. Chem. 1996, 61, 826 31) Hui, B.C Inorg. Chem. 1980, 19, 3185
*For Online Consulting Only
press -F for Searching
62
Rohm and Haas : the Sodium Borohydride Digest
ESTERS Alembic: 10, 36, 48, 50, 55, 57, 60, 61 Traditionally the reduction of simple aliphatic esters with sodium borohydride in protolytic solvents is extremely slow and therefore not practical for industrial processes. In aprotic solvents such as dichloromethane, the reduction of ethyl laurate with the soluble tetrabutylammonium borohydride is only 25% complete after 4 days at 25oC (1). In comparison tetrabutylammonium borohydride in CCl3H at reflux temperatures will reduce aliphatic esters to alcohols in 70 % yields after 5h (2). A large number of “activated” esters can be reduced directly with sodium borohydride in protolytic solvents. Electron withdrawing groups alpha to the ester carbonyl group increase the positive charge on the carbonyl carbon making it much more susceptible to attack by the borohydride ion (3). Examples of electron withdrawing groups and their borohydride reduction products are: Hydroxyl-Sugar EstersÆ Primary alcohols (4-7). and Lactones
*For Online Consulting Only
63
press -F for Searching OH
O O
NaBH4
O
OEt
O
O H
pH 2-3
H
In the case of ket-esters, both keto and ester groups are reduced to give a diol (8-11). The reduction of alpha-amino esters gives optically active alpha amino alcohols (12,13). Alpha chloroamines also activate esters for borohydride reduction (14). NH3+ClOCH3 NaBH4 O
NH3+ClH H OH
Amido and thioamido groups residing on the carbon next to ester group activates the ester group so that it can be reduced with sodium borohydride at R.T. (15) Alpha epoxy esters are reduced to epoxy alcohols (16,17) in the presence of nitrile groups.
O
O
H
OCH3 NaBH4 O
H
Similarly, the following reduction in anhydrous solvents using potassium borohydride has been reported (21). EtO2C(CF2)3CO2EtÆ HOC(CF2)3COH
OH
Very rapid reductions of alpha-chloroesters to their corresponding alcohols have been reported as part of the amine ester study mentioned above (12,18). Similarly, the following reduction is reported (19). OCH3
H
O Cl
N
HO NaBH4
H Cl
CH3
N
N
Processes have been patented (22,23) for the reduction of perfluoroesters and acids with NaBH4 to the corresponding alcohol. Cyano- Like the halogens, the alpha-cyano group is a powerful electron withdrawing group and activates borohydride reduction of the ester group as illustrated below: (24- 26)
OCH3
N
A series of fluoronitroesters have been reduced to the corresponding alcohols with sodium borohydride in water (20). R
O2N O
OR NaBH4 H2O
*For Online Consulting Only
F
OH
O
CH3
O
F
64
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest
N
H H OH
O
N
H
H (24)
Ph
Ph Ph
CN
R
O2N
NaBH4
Ph O
NaBH4
Ph
diglyme OEt 15-20 oC Ph
CN
(25) H H
HO
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest R
CN
R
NaBH4
R
OEt EtOH
R
O
H
CN NaBH4 R H OEt
H
CN H (26) H H
R
O
HO
The ester groups of a series of triglycerides from virgin olive oil can be selectively reduced with sodium borohydride to form their corresponding alcohols in high yields. (27) Miscellaneous: Examples of other activated esters, which have been reduced with sodium borohydride, are (28-30) O
OH
O OCH3 NaBH4 H
H3CO
OH
H
H
H
(28)
EtOH
O
OCH3 NH2
N H2N
N
HO NaBH4
NH2
H H NH2
N H2N
(29) N
NH2
N-Acyldipeptide ester Æ Amino Alcohol (30)
*For Online Consulting Only
65
The acyl groups in lecithin and monogalactosyl diglycerides were reduced by sodium borohydride to fatty alcohols with no detectable reduction or isomerization of double bonds in 94 and 64% yield, respectively (31) Changing the alcohol portion of the ester group can facilitate the borohydride reduction of the ester. It has been reported (32) that the reduction of esters of alcohols more electronegative than methyl, such as phenol and other acidic alcohols, can increase reduction rates by 300fold. Another technique that is effective to reduce esters is to modify the cation associated with the borohydride anion. Lithium borohydride will reduce most esters quite easily (33). The enhanced reduction effect of the lithium ion is greatest in solvents of low dielectric constants. In such solvents, the reaction presumably proceeds through the ionpair (Li+BH4-) rather than through the completely dissociated ions. Magnesium borohydride and calcium borohydride probably behave in a similar manner. The reactions of sodium or potassium borohydride with lithium chloride, magnesium chloride or calcium chloride in tetrahydrofuran, diglyme or ethanol give the corresponding lithium, magnesium or calcium borohydrides by metathesis. Reducing systems based on these reactions can be used for ester reductions by in situ preparative techniques without removal of the by-product alkali metal chloride (34-41 ). Olefins have been demonstrated to increases the reactivity of calcium borohydride towards the reduction of
Rohm and Haas : the Sodium Borohydride Digest
esters group.(42) This technique works for reducing aromatic and aliphatic esters to alcohols. The addition of olefins to Zn(BH4)2 also increase the reactivity of the Zn(BH4)2 towards the reduction of esters.(43) Other catalyst which have demonstrated to increase reactivity of metal borohydride towards the reduction of esters are trialkyl borates and amines. (4446) Clear diglyme solutions of aluminum chloride and sodium borohydride (molar ratio 1:3) easily reduce esters to alcohols, but other functional groups and double bonds are also reduced (47-48). A study on the effect of metal halides on the reducing properties of sodium borohydride in aprotic solvents has been published (49). Cuprous halide gave a reagent specific for the reduction of carboxylic acids, and TeCl4or ThCl4 gave systems specific for the reduction of esters and acids. Zirconium tetrahalides produced a very strong reducing system that attacked all functional groups including reduction of nitro groups at room temperature. An extensive evaluation of cation and solvent effects on the borohydride reduction of carboxylic esters has been published (50). It is also possible to modify the BH4- anion to greatly enhance its reactivity. Many esters have been reduced with large excesses of sodium borohydride in
*For Online Consulting Only
66
press -F for Searching
refluxing methanol (51-52). It is believed now that the active reducing species was sodium trimethoxyborohydride which was formed in situ. Sodium acetanilidoborohydride has been synthesized by the reaction of acetamilide (or benzanilide) in α-picoline. This reagent reduced methyl esters in good yields without affecting other functional groups (amide, nitro and isopropyl ester) (53-54). O H3C
N
H
O
Ph +
NaBH4
H3C
BH3-Na+ + H2
N Ph
Another system involves refluxing sodium borohydride with ethanedithiol in dry THF along with the ester has been described (55-56). Benzoate and aliphatic esters were reduced and methyl cinnamate was reduced to 3-phenyl propanol. A large number of aliphatic and aromatic acids and esters have been reduced by sodium borohydride in the presence or absence of a solvent at high temperatures. Reductions using 1 equivalent of NaBH4 gave the corresponding alcohols (57).
Rohm and Haas : the Sodium Borohydride Digest
A novel approach to ester reductions is the slow addition of methanol to a refluxing mixture of the ester and NaBH4 in tert-butanol or tetrahydrofuran (5859), resulting chemoselectively in high yields of primary alcohols. This system has been applied successfully to the preparation of N-protected amino alcohols and N-protected peptide alcohols. NaBH4 in diglyme at elevated temperatures reduces aromatic ester to alcohols while at RT no reaction occurs. (60) Both aromatic and aliphatic esters are reduced to alcohols with NaBH4 in water or a 1:1 mixture of water and dioxane at RT. ( 61) Sodium borohydride when combined with reagents such as Me3SiCl or I2 form borane BH3, which will reduce both aromatic and aliphatic esters chemoselectively. (62-63) Esters can be converted to aldehydes by oxidizing the borate ester intermediate formed from the reduction of esters with calcium borohydride ( 64).
*For Online Consulting Only
press -F for Searching
67
References: 1) Raber, D.J.; Guida, W.C. J. Org. Chem. 1976, 41 690; Chem. Abstr. 84 880n 2) Narasimhan, S.; Swarnlakshmi, S.; Balakumar, R.; Velmathi, S. Synlett. 1998. 1321 3) Schenker, E. "Newer Methods of Preparative Organic Chemisty", Vol IV, 1968, 196, Verlang, Chemie, Weinheim 4) Wolfrom, M.L.; Anno, K. J. Am. Chem. Soc. 1952, 74, 5583; Chem. Abstr. 8, 134e 5) Wolfrom, M.L.; Wood, H.B. J. Am. Chem. Soc. 1951, 73, 2933; Chem. Abstr. 46, 3961a 6) Barton, D.H.R. et. al. J. Chem. Soc. Perkin Trans. 1 1975, 2069; Chem. Abstr. 84, 31342b 7) Ger. Offern. 2,911,377, 1980; Chem. Abstr. 94, 121935h 8) Heymann, H.; Fiesser, L.F. J. Am. Chem. Soc. 1951, 73, 5252; Chem. Abstr. 47, 592d 9) Leonard, N.J.; Conrow, K.; Fulmer, R.W. J. Org. Chem. 1957, 22, 1445; Chem. Abstr. 52, 8134c 10) Soai, K.; Oyamada, H. Synthesis 1984, 605; Chem. Abstr. 101, 229944n 11) Brown, G.R.; Foubister, A.J. J. Chem. Soc., Chem. Commun. 1985, 455; Chem. Abstr. 103, 122724e 12) Seki, H. et. al. Chem. Pharm. Bull. 1965, 13, 995; Chem. Abstr. 63, 14971d
Rohm and Haas : the Sodium Borohydride Digest
13) Mandal, S.B.; Achari, B.; Chattopadyay, S. Tetrahedron Lett. 1992, 33, 1647 14) Macmillan, J.G. et. al. J. Am. Chem. Soc. 1976, 98, 246; Chem. Abstr. 84, 90114b 15) Roy, A.; Bar, N.C.; Achari, B.; Mandal, S.B. Indian J. Chem. 1998, 37b, 644 16) Corsano, S.; Pncetelli, G. J. Chem. Soc., Chem. Commun. 1971, 1106; Chem. Abstr. 75, 151935h 17) Mauger, J.; Robert, A. J. Chem. Soc.; Chem. Commun. 1986, 395 18) Seki, H.; Koga, K.; Yamada, S. Chem. Pharm. Bull. 1967, 15, 1948; Chem. Abstr. 69, 107039w 19) Beyereman, H.C.; Maat, L.; Noordam, A; Van Zon, A. Recl. Trav. Chim. Pays-Bas 1977, 96, 222; Chem. Abstr. 88, 70328p 20) U.S. 3,783,144 1974; Chem. Abstr 80, 70328p 21) Dobina, K.A. et. al. Zh. Prikl. Khim. 1973, 46, 678; Chem. Abstr. 79, 4911b 22) French 1,573,705 1969; Chem.Absr. 72, 100009q 23) Jpn. Kokai Tokkyo Koho 83 85,832 1983; Chem. Abstr. 99,104774r 24) Paul, R.; Williams, R.P.; Cohen, E. J.Org. Chem. 1975, 40, 1653; Chem. Abstr. 83, 192471n 25) Meschino, J.A.; Bond, C.H.; J. Org. Chem. 1963, 28, 3129; Chem. Abstr. 59, 15280f
*For Online Consulting Only
press -F for Searching
68
26) Marshall, J.A.; Caroll, R.D. J. Org. Chem. 1965, 30, 2748; Chem. Abstr. 63, 11387d 27) Giumanini, A.G.; Tubaro, F. J. Prakt. Chemie. Band 1990, 332, 755 28) Span. 41324 1976; Chem. Abstr. 86, 106401x 29) Wong, J.; Brown, M.S.; Matsumoto, K.; Oesterlin, R.; Rapoport, H. J. Am. Chem. Soc. 1971, 93, 4633; Chem. Avstr. 86, 106401x 30) Yonemitsu, O.; Hamada, .; Kanaoka, Y. Tetrahedron Lett. 1968, 3575; Chem. Abstr. 69, 87454x 31) Nichols, B.W.; Safford, R. Chem. Phys. Lipids 1973, 11, 222 Chem. Abstr. 80, 47412 32) Takahashi, S.; Cohen, L.A. J. Org. Chem. 1970, 35, 1505; Chem. Abstr. 73, 3270f 33) Nystrom, R.F.; Chaikin, S.W.; Brown, W.G. J. Am. Chem. Soc. 1949, 71, 3245; Chem. Abstr. 44, 1017e 34) Paul, R.; Joseph, N. Bull. Soc. Chim. France 1952, 550; Chem. Abstr. 47, 32651 35) Kollonitsch, J. Fuchs, O.; Gabor, V Nature 1955, 175, 346; Chem. Abstr. 50, 1774d 36) Brown, H.C.; Mead, E.J.; Subba Rao, B.C.; J. Am. Chem. Soc. 1955, 77, 6209; Chem. Abstr. 50, 8529h 37) Jpn. Kokai Tokkyo Koho 80, 133,369, 1980; Chem. Abstr. 94, 174915h 38) U.S.; 4512,991 1985; Chem. Abstr. 103, 71338x
Rohm and Haas : the Sodium Borohydride Digest
39) Jpn. Kokai, Tokkyo Koho 85, 178,845 1985; Chem. Abstr. 104 88116s 40) Brisse, F.; Durocher, G. et.al. J. Am. Chem. Soc. 1986, 108, 6579 41) Dieks, H.; Senge, M.O.; Kirste, B.; Kurreck, H. J. Org. Chem. 1997, 62, 8666 42) Narasimhan, S.; Prasad, G.; Madhavan, S. Synth. Commun. 1995, 25, 1689 43) Narashhan, S.; Madhavan,S.; Prasad, K. Synth. Commun. 1997, 27, 385 44) Brown, H.C.; Narasimhan, S. J. Org. Chem. 1982, 47, 1604 45) Yamakawa, T. Masaki, M.; Nohira, H. Bull. Chem. Soc. Jpn. 1991, 64, 2730 46) Ranu, B.C.; Basu, M.K. Tetrahedron Lett. 1991, 32, 3243 47) Brown, H.C.; Subba Rao J. Am. Chem. Soc. 1956, 78, 2582; Chem. Abstr. 51, 1077c 48) U.S. 4,842,775 1989 49) Subba Rao, B.C.; Thakar, G.P.; J. Sci. Industr. Res. 1961, 0b, 317; Chem. Abstr. 56, 6881h 50) Brown, H.C.; Narasimhan, S; Choi, Y.M. J. Org. Chem. 1982, 47, 4702; Chem. Abstr. 97, 197647y 51) Brown, M.S.; Rapoport, H. J. Org. Chem. 1963, 28, 3261; Chem. Abstr. 60, 2924d
*For Online Consulting Only
press -F for Searching
69
52) Zanka, A.; Ohmori, H.; Okamoto, T. Synlett 1999, 10, 1636 53) Kikugawa, Y. Chem. Lett. 1975, 1029; Chem. Abstr. 83, 192759n 54) Kikugawa, Y. Chem. Pharm. Bull. 1976, 24, 1059; Chem. Abstr. 85, 108365s 55) Maki, Y.; Kikuchi, K.; Sugiyama, H. Set, S. Tetrahedron Lett. 1975, 3295; Chem. Abstr. 83, 192758m 56) Guida, W.C.; Entreken, E.E.; Guida, A.R.; J Org. Chem. 1984, 40, 3024; Chem. Abstr. 101, 72355w 57) Nose, A.; Kudo, T.; Yakugaku Zasshi 1976, 96, 1401; Chem. Abstr. 86, 139533v 58) Soai, K.; Oyamada, H.; Takase,M.; Ookawa, A. Bull. Chem. Soc. Jpn. 1984, 57, 1948; Chem. Abstr. 101, 230087s 59) Soai, K.; Oyamada, H.; Takase, M. Bull. Chem. Soc. Jpn. 1984, 57, 2327; Chem. Abstr. 101, 192464c 60) Yang, C.; Pittman, C.U. Synthetic Commun. 1998, 28, 2027 61) Binco, A.; Passacantilli, P. Righi, G. Synth. Commun. 1988, 18, 1765 62) Prasa, A.S.B.; Kanth, J.V.b.; Periasamy, M. Tetrahedron, 1992, 48, 4623 63) Giannis, A.; Sandhoff, K. Angew. Chem. Int. Ed. Engl. 1989, 28, 218
Rohm and Haas : the Sodium Borohydride Digest
64) Narasimhan, S.; Ganeshwar, K.; Madhavan, S. Synth. Commun. 1995, 25, 1689
*For Online Consulting Only
press -F for Searching
70
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
71
ENOL ESTERS In mixed solvent systems containing water, NaBH4 reduces enol esters to the alcohol. The enol ester is first hydrolyzed to the ketone, which is reduced by the borohydride: NaBH4
H2O Aco
HO
HO
Cholestenone has been reduced to cholesterol in good yield via the enol ester route (1). Enol ester reductions are applied most frequently in steroid synthesis (2-6).
*For Online Consulting Only
References: 1) Belleau, B.; Gallagher, T.F. J. Am. Chem. Soc. 1951, 73, 4458; Chem. Abstr. 47, 138I 2) Kurath, P.; Capezzuto, M. J. Am. Chem. Soc. 1956, 78, 3527; Chem. Abstr. 51, 1229h 3) Djerassi, C. et. al. J. Am. Chem. Soc. 1958, 80, 2596; Chem. Abstr. 52, 20262a 4) Smith, S.H.; Turner, A.B. J. Chem. Soc. Perkin 1 1975, 1751; Chem. Abstr. 84 5241y 5) Gruenke, L.D.; Craig, J.C. J. Labeled Compd. Radiopharm. 1979, 16, 495; Chem. Abstr. 92, 59077h 6) Fendrich, G.; Abeles, R.H. Biochemistry 1982, 21, 6685; Chem. Abstr. 98, 2166f
72
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest
O
IMIDES While broadly definitive papers on the imide reductions by NaBH4 have not appeared in the literature, many specific reductions have been described and the products obtained vary with starting imide. In some cases, carbonyl reductions accompanied by ring opening are obtained. For example, several cyclic imides have been reduced by sodium borohydride in methanol as shown below(1). R
HO
O
Me N
Ph
R
NaBH4
O
Me R
H N
Ph
H N
Ph
O Me
HO O
Examples of reduction of substituted succinimides, glutarimides and 3-nitrophthalimide by sodium borohydride in isopropanol have also been reported (2,3). The acid catalyzed borohydride reduction of imides also has been described (4-6).
*For Online Consulting Only
N CH 3
Me
N CH (84%) 3
Me
O
OH
NaBH4
OH (16%)
O
N CH 3
Me O
Tetrahydrothalimide derivatives have been reduced with sodium borohydride in ethanol (7). Various other imide reductions are cited in the literature (8-15). Imidic ethers have been reduced with the system NaBH4/SnCl4 dietherate in gylme at 0 oC (16). H
OEt NH
NaBH4
H NH2
SnCl4
Stereoselective reduction of imides to hydroxy lactam can be achieved by reacting imides with tetramethylammonium triacetoxy borohydride, NaBH4 with magnesium perchlorate and NaBH4 with CeCl3. (17-19)
Rohm and Haas : the Sodium Borohydride Digest
Cyclic Imides can be deoxygenated to form cyclic amines in high yields using NaBH4 with I2 or H2SO4. (20) References: 1) Ohki, S. et. al Yakugaku Zasshi 1973, 93, 841; Chem. Abstr. 79, 91872f 2) Watanabe, T.; Hamaguchi, F.; Ohki, S. Yakugaku Zasshi 1973, 93, 845; Chem. Abstr. 79, 78328p 3) Watanabe T. Hamaguchi, F.; Ohki, S.; Chem. Pharm. Bull. 1972, 20, 2123; Chem. Abstr. 78, 4058h 4) Wijnberg, J.; Speckamp, W. Tetrahedron 1975, 31, 1437; Chem. Abstr. 84, 59813e 5) Wijnberg, J.; Speckamp, W. Tetrahedron 1975, 31, 4035; Chem. Abstr. 84, 74482q 6) Hubert, J.C.; Wijnberg, J.; Speckamp, W. Tetrahedron 1975, 31, 1437; Chem. Abstr. 83, 147364u 7) Zielinski, T.; Esztajn, J.Jatczak, M. Rocz. Chem. 1975, 49, 1671; Chem. Abstr. 84, 150433s 8) Iida, H.; Takahaski, K.; Kikuchi, T; Heterocycles 1976, 4, 1497; Chem. Abstr. 86, 29596k 9) Newman, H. J. Org. Chem. 1974, 39, 100; Chem. Abstr. 80, 95165w
*For Online Consulting Only
press -F for Searching
73
10) Martin, M.G.; Ganem, B. Tetrahedron Lett. 1984, 25, 2093; Chem. Abstr. 101, 131057a 11) Burnett, D.A.; Choi, J.-K., hart, D.J.; Tsai, Y.M. J. Am. Chem. Soc. 1984, 106, 8201; Chem. Abstr. 012, 79186w 12) Trehan, I.R.; Kad, G.L.; Rani, S.; Bala, R. Inidian J. Chem, Sec B 1985, 24B, 659; Chem. Abstr. 104, 225089b 13) Ger. Offen. 3,446,303 1986; Chem. Abstr. 105, 153331v 14) Koot, W.J.; VanGinkel, R.; Kraneburg, M.; Hiemstra, H.; Louwier, S.; Moolemaar, M.J.; Speckamp, W.N. Tetrahedron Lett. 1991, 32, 401 15) Leban, J.J.; Colson, K.L. J. Org. Chem. 1996, 61, 228 16) Tsuda, Y.; Sano, T.; Watanabe, H. Synthesis 1977, 652; Chem. Abstr. 88, 36668e 17) Miller, S.A.; Chamberlin, A.R. J. Org. Chem. 1989, 54, 2502 18) Konopikova, M.; Fisera, L.; Pronayova, N.; Ertl, P. Liebigs, Amn. Chem. 1993, 1047 19) Deprez, P.; Royer, J.; Husson, H.P. Tetrahedron 1993, 49, 3781 20) U.S. 5585500 1996
74
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest
Glycidic lactones Æ glycidol loactols (10)
LACTONES Alembic: 50
O
Sodium borohydride has been used extensively for the reduction of lactones mainly in the synthesis of complex organic fine chemicals and pharmaceuticals. Reductions are best carried out in water, alcohols or mixtures of these solvents. Yields are generally acceptable but may require use of an excess of sodium borohydride. Lactones that resist reduction with sodium borohydride in protic solvents usually can be reduced with NaBH4 and AlCl3 in diglyme (1). But recently it has been demonstrated that sodium borohydride in MeOH can reduce lactones (2) No definitive study of borohydride reduction of lactones has been published. Nevertheless, the application is well established (3-5). Some selected examples are:
R
O
O NaBH4 X
R
R
polysaccharides loactones Æ aldose (6-9)
*For Online Consulting Only
O
O
O O
N
O
OH
OH
H3C NaBH4
H3C
H3C
(11)
HN
Ph
Ph
Lithocarpic lactone
H H O
O X
O
H3C
O
O R
O NaBH4
O
PGF2
H
H
H NaBH4
HO HO
H
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest O
O O
O
NaBH4 O
O
(13) HO
HO
Aflatoxins B1 and B2 O
OH
O
O
OH
O NaBH4 O
(14)
O
O
O
OCH3
OCH3
Production of N-(dihydroxyalkyl) uracils O
O
N O
O
N N
O
NaBH4
HO
O
N
(15,16)
HO
The use of lanthanide metal salts with sodium borohydride has been shown to reduce lactone efficiently. (17) Stereoselective reduction of a lactone to α-hydroxy cyclic ether has been accomplished by *For Online Consulting Only
75
using cyclodextrans as a template. (18) Sodium borohydride has been shown to also convert lactones to α-hydroxy cyclic ether in high yield (19) References: 1) 1)Brown, H.C.; Subba Rao, B.C.; J. Am. Chem. Soc. 1956, 78, 2582; Chem. Abstr. 51, 1077c 2) Di Nardo, C.; Jerancic, L.O. de Lederkremer, R.M.; Varela, O. J. Org. Chem. 1996, 61, 4007 3) Hsu, C.T.; Wang, N.Y.; Latimer, L.H.; Shih, C.J. J. Am. Chem. Soc. 1983, 105, 593; Chem. Abstr. 98, 107052u 4) Kametani, T.; Tsubuki, M.; Furuyama, H.; Honda, T.J. J. chem. Soc. Perkin 1 1985, 557; Chem. Abstr. 103, 6604s 5) Jpn. Kokai Tokkyo Koho 85,224,684 1985; Chem. Abstr. 104, 109358q 6) Wolfrom, M.L.; Wood, H.B. J. Am. Chem. Soc. 1951; 73; 2933; Chem. Abstr. 46, 3961a 7) Wolfom, M.L.; Anno, K. J. Am. Chem. Soc. 1952, 74, 5583; Chem. Abstr. 48, 134e 8) Frush, H.L.; Isbell, H.S. J. Am. Chem. Soc. 1956, 78, 2844; Chem. Abstr. 14533h 9) Shenai, V.A.; Sdudan, R.K. J. Appl. Polym. Sci. 1972, 16, 545; Chem. Abstr. 76, 155353k 10) Corsano, S.; Piancatelli, G. J. Chem. Soc., Chem. Commun. 1971, 1106; Chem. Abstr. 75, 151935h
Rohm and Haas : the Sodium Borohydride Digest
11) Truitt, P.; Chakravarty, J. J. Org. Chem. 1970, 35, 864; Chem. Abstr. 72, 100568w 12) Hui, W.H.; Moon, L.M.; Lee, L.C. J. Chem. Soc., Perkin Trans 1 1975, 617; Chem. Avstr. 83, 10489u 13) Woodward, R.B. et. al. J. Am. Chem. Soc. 1973, 95, 6853; Chem. Abstr. 809, 3140h 14) Ashoor, S.H.; Chu, F.S. J. Assoc. Off. Anal. Chem. 1975, 58, 492; Chem. Abstr. 83, 109529u 15) Brit. 1,393,863 1975; Chem. Abstr. 84, 4991f 16) Hillers, S.; Zhuk, R.A.; Berzina,A.; Kaulina, L. Khim. Geterotsikl. Soedin. 1975, 694; Chem. Abstr. 83, 114332d 17) Masaguer, C.F.; Bleriot, Y.; Charlwood, J.; Winchester, B.G.; Fleet, G.W.J. Tetrahedron 1997, 44, 15147 18) Pitchumani, K.; Velusamy, P.; Srinivsan, C. Tetrahedron 1994, 50, 12979 19) Wu, H.J.; Tsai, S..; Chern, J.H.; Lin, H.C. J. Org. Chem. 1997, 62, 6367
*For Online Consulting Only
press -F for Searching
76
77
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest
D. Carbon Nitrogen Compounds N
REDUCTIVE AMINATION Alembic: 6, 7, 28, 52, 55 The little known reaction of N-ethylation of amines by a combination of formaldehyde and sodium borohydride involves the sequential treatment of a primary or secondary amine with the reagents. It is analogous to the Eschweiler-Clarke reaction, except that reduction of the imine or immonium intermediate with sodium borohydride occurs at room temperature, instead of requiring reflux conditions on the steam bath. This reaction has found most frequent us in alkaloid synthesis, to convert cyclic amines to their Nmethyl derivatives, the tetrahydroisoquinoline nucleus being the most common substrate (1-5) NaBH4 N
H CH2=O
N
CH3
Closely related structures in aporphines have also been methylated with fomaldeyde- NaBH4 (6,7). *For Online Consulting Only
N
H NaBH4
CH3
CH2=O
Two additional references (8,9) report the methylation of tetrahydropteridines in similar fashion. These are especially noteworthy because the pteridine nucleus is selectively methylated at the N-5 position. H
H N N H
N
NaBH4 N CH2=O
N N
N N
CH3
The utility of this reaction is by no means limited to heterocyclic amines. Conversions to methyl tertiary amino substituents in steroid systems have been reported (10-12). Numerous other systems (13) have been described including dibenzoxepis (14), Biological species (15), Amnonucleosides
Rohm and Haas : the Sodium Borohydride Digest
(16) and β-alkanolamines- via the readily formed oxazolidins (17). The methylation reaction has been applied to organometallic specifically α-ferrocenylethylamine (18) and α-ferrocenylbenzylamine (19). Alkylation using NaBH4 in the presence of lower aliphatic carboxylic acids have been investigate extensively by Gribble (20-24) and exploited by others (25-33). Giumanini has shown that the combination of carboxylic acid and sodium borohydride can N-alkylate hydrazides in high yields. (34) Formaldehyde can be replaced by a number of reagents in this reaction, e.g. ClCOOMe (to give NCOOMe) (35,36), other aldehydes (37) and aryl halides (38). Sodium cyanoborohydride has become a popular alternative reducing agent for reductive alkylations. (39-48) Metal modifiers such as TiCl4, Ti(OiPr)4 and ZnCl2 with borohydrides can reductively aminate ketones and aldehydes to form 2o and 3o amines.(49-58) The use of aprotic solvents such as hexane as a reaction medium with solid supports such as silica gel and clays for the reductive amination of aldehydes and ketones by borohydride have been demonstrated to be highly efficient.(59,60) Borohydride exchange resins can also
*For Online Consulting Only
press -F for Searching
78
induce reductive amination of aldehydes and ketones in high yields in methanolic solutions. (61,62) Reductive amination of ketones and aldehydes can be accomplished in high yields using sodium borohydride with sulfuric acid.(63-67). References: 1) Konda, M.; Ohishi, T.; Yamada, S. Chem. Pahrm. Bull. 1977, 25, 69; Chem. Abstr. 86, 171684f 2) Kupchan, S.M.; Leipa, A.;J. Baxter, R.L.; Hintz, H.P. J. Org. Chem. 1973, 38, 1846; Chem. Abstr. 790, 5482z 3) Dwama-Badu, D. et al. Experientia 1975, 31, 1251; Chem. Abstr. 84, 90377q 4) Teitel, S.; O’Brian, J.P. Heterocycles 1974, 2, 625; Chem. Bastr. 84, 90377q 5) Cava, M.P.; Noguchi, I; Buck, K.T. J. Org. Chem. 1973, 38, 2394; Chem. Absytr. 79, 42715y 6) Kupchan, S.M.; Dhingra, O.P.; Kim, C.K.; Kanewaran, V. J. Org. Chem. 1976, 41, 4047; Chem. Abstr. 86, 72937j 7) Kametani, T. Et. Al. J. Chem. Soc. C 1971, 1032; Chem. Abstr. 74, 142122t 8) Gupta, V.S.; Huennekens,F.M. Ach. Biochem. Biophys. 1967, 120, 712; Chem. Abstr. 67, 100112q 9) Whiteley, J.M.; Drais, J.H.; Huennekens, F.M. Arch. Biochem. Biophys. 1969, 133, 436; Chem. Abstr. 71, 101824t
Rohm and Haas : the Sodium Borohydride Digest
10) Cava, A.; Poiter, P.; LeMen, J. Bull. Soc. Chim. France 1965, 2502; Chem. Abstr. 63, 16409a 11) Husson, H.P.; Potier, P.; LeMen, J. Bull. Soc. Chim. France 1966, 948; Chem. Abstr. 65, 2328d 12) Sondengam, B.L. Hemo, J.H.; Charles, G. Tetrahedron. Lett. 1973, 261; Chem. Abstr. 78, 124800r 13) Ger. Offen. 3,405,334 1985; Chem. Abstr. 104, 129795h 14) Bickelhaupt, F.; Stach, K.; Thiel, M. Monatsh. 1965, 95, 485; Chem. Abstr. 61, 5575h 15) Chovath, B.; Duraj, J; Sedlak, J. Neoplasma 1985, 32, 393; Chem. Abstr. 104, 105457y 16) Morr, M.; Ernest, L. J. Chem. Res. (S) 1981, 90; Chem. Abstr. 95, 98193z 17) Saavedra, J.E. J. Org. Chem. 1985, 50, 2271; Chem. Abstr. 103, 22139z 18) Gokel, G. et. al. Angew. Chem. Int. Ed. Engl. 1970, 9, 64; Chem. Abstr. 72, 6707d 19) Allenmark, S; Kalen, K Tetrahedron Lett. 1975, 3175; Chem. Abstr. 83, 206401d 20) Gribble, G.N.; Jasinski, J.M.; Pellicone, J.T.; Panetta, J.A. Synthesis 1978, 766; Chem. Abstr. 72, 67071d 21) Gribble, G.N.; Wright, S.W.; Hetercycles 1982, 19, 229; Chem. Abstr. 96, 162482t
*For Online Consulting Only
press -F for Searching
79
22) Gribble, G.N.; Nutaitis, C.F.; Leese, R.M. Heterocycles 1984, 22, 379; Chem. Abstr. 102, 38296t 23) Gribble, G.W. ACS. Semposium Series 1996, 641, 167 24) Gribble, G.W. Chemical Soc. Reviews 1998, 27, 395 25) U.S. 4,378,368 1983; Chem. Abstr. 99, 16566u 26) Eur. Pat. Appl. 122,831 1984; Chem. Abstr. 102, 77872e 27) Ramajulu, J.M.; Joulle, M.M. Synth. Commun. 1996, 26, 1379 28) Pegorier, L.; Petit, Y.; Larcheveque, M. J. Chem. Soc., Chem. Commun. 1994, 633 29) Abdel-Magid, A.F.; Carson, K.G.; Harris, B.D.; Maryanoff, C.A.; Shah, R.D. J. Org. Chem. 1996, 61, 3849 30) Yang, L.X. Hofer, K.G. Tetrahedron Lett. 1996, 37, 6081 31) Yang, Z.; Bradshaw, J.S.; Zhang, X.X.; Savage, P.B.; Kralowiak, K.E.; Dalley, N.K.; Su, N.; Bronson, R.T.; Izatt, R.M. J. Org. Chem. 1999, 64, 3162 32) Ramanjulu, J.M.; Joullie, M.M. Synth. Commun. 1996, 26, 1379 33) Abdel-Magid, A.F.; Marynoff, C.A.; Carson, K.G. Tetrahedron Lett. 1990, 31, 5595 34) Verardo, G.; Toniutti, N.; Giumanini, A.G. Can. J. Chem. 1998, 76, 1180 35) Tsuchiya, T.; Kurita, J.; Snieckus, V. J. Org. Chem. 1977, 42, 1856
Rohm and Haas : the Sodium Borohydride Digest
36) Fowler, F.W. J. Org. Chem. 1972, 37, 1321; Chem. Abstr. 77, 19494a 37) Eur. Pat. Appl. 112,606 1984; Chem. Abstr. 101, 231039q 38) Kutey, J.P.; Greenhouse, R.; Ridaura, V.E. J. Am. Chem. Soc. 1974, 96, 7364; Chem. Abstr. 82, 16672z 39) Harding, K.E.; Clements, K.S. J. Org. Chem. 1984, 49, 3870; Chem. Abstr. 101, 171542m 40) Keck, G.E.; Enholm, E.J. J. Org. Chem. 1985, 50, 146; Chem. Abstr. 102, 45160t 41) Eur. Pat. Appl. 155,079 1985; Chem. Abstr. 104, 168094y 42) Ger. Offen. 3,507,019 1986; Chem.Abstr. 105, 227237t 43) Zhao, H.; Mootoo, D.R. J. Org. Chem. 1996, 61, 6762 44) Szardening, A.K.; Burkoth, T.S.; Look, G.C.; Cambell, D.A. J. Org. Chem. 1996, 61, 6720 45) Saavedra, O.M.; Martin, O.R. J. Org. Chem. 1996, 61, 6987 46) Boga, C.; Manescalchi, F.; Savoia, D.; Tetrahedron 1994, 50, 4709 47) Barney, C.L.; Huber, E.W.; McCarthy, J.R. Tetrahedron Lett. 1990, 31, 5547
*For Online Consulting Only
press -F for Searching
80
48) Manescalchi, F.; Nardi, A.R.; Savoia, D. Tetrahedron Lett. 1994, 35, 2775 49) Bhattacharyya, S. J. Org. Chem. 1995, 60, 4928 50) Bhattacharyya, S. Tetrahedron Lett. 1994, 35, 2401 51) Neidigh, K.A.; Avery, M.A.; Williamson, J.S.; Bhattacharyya, S. J. Chem. Soc., Perkin Trans. 1 1988, 2527 52) Armstrong, J.D.; Wolfe, C.N.; Keller, J.L.; Lynch, J.L.; Bhupathy, M.; Volante, R.P.; 53) DeVita, R.J. Tetrahedron Lett. 1997, 38, 1531 53) Bhattacharya, S.; Chatterjee, A.; Williamson, J.S. Synlett 1995, 1079 54) Bhattacharyya, S. Synth. Commun. 1995, 25, 2061 55) Bhattacharyya, S.; Chatterjee, A.; Williamson, J.S. Synth. Commun. 1997, 27, 4265 56) Bhattachryya, S.; Chatterjee, A.; Duttaachowdhury, S.K. J. Chem. Soc. Perkin. Trans. 1 1994, 1 57) Kim, S.; Oh, C.H.; Ko, J.S.; Ahn, K.H.; Kim, Y.J. J. Org. Chem. 1985, 50, 1927 58) Ranu, B.C.; Majee, A.; Sarkar, A. J. Org. Chem. 1998, 63, 370 59) Varma, R.S.; Dahiya, R. Tetrahedron, 1998, 54, 6293 60) Nah, J.H.; Kim, S.Y.; Yoon, N.M. Bull. Korean, Chem. Soc. 1998, 19, 269 61) Yoon, N.M.; Kim, E.G.; Son, H.S.; Choi, J. Synth. Commun. 1993, 23, 1595
Rohm and Haas : the Sodium Borohydride Digest
62) Verardo, G.; Giumanini, A.G.; Strazzolini, P.; Poiana, M. Synthesis 1993, 121 63) Verardo, G.; Giumanini, A.G.; Strazzolini, P. Synth. Commun. 1994, 24, 609 64) Vyskocil, S.; Smrcina, M.; Hanus, V.; Polasek, H.; Kocovsky, P. J. Org. Chem. 1998, 63, 7738 65) Giumanini, A.G.; Verardo, G. Gei, M.H.; Lassiani, L. J. Labelled Compd. Radiopharm. 1987, 24, 255 66) Verardo, G.; Giumanini, A.G. Strazzolini, P.; Poiana, M. Synthesis 1991, 6, 447
*For Online Consulting Only
press -F for Searching
81
AZIDES Alembic: 50, 52, 55, 58
N3
O
Ac
*For Online Consulting Only
O
H H
X
N Ac
O
H H
H H NH2
OH
O
O2N
OH N3
NH
NaBH4
O2N
OH NH
Cl2HC
Cl2HC O
O
This reduction has been applied to chloramphenicol synthesis (7). "RR'N
S N
X
NaBH4 H N3
OH
N
HO
H
OH
CH3 CH3
O
NaBH4
O
N
HO
NH2
X
HN
HN
Highest yields were achieved when caustic was added to stabilize the borohydride in an aqueous dioxane solvent system. The conversion of azides to amines by conventional methods cannot be employed if sulfur is present in the compound. NaBH4 in isopropanol is effective if no other easily reducible group is present, and is useful for acidsensitive compounds (2-6).
N
O
O
Acyl and aromatic azides (but not monofunctional aliphatic azides) are reduced to the corresponding primary amine as reported by Boyer and Elizer (1). 4 RN3 + NaBH4 Æ 4 RNH2 R = acyl, aryl or sulfonly group.
X
82
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest
O
N3
"RR'N
S
NaBH4
CH3
N
CH3
O HO
H
H
Rohm and Haas : the Sodium Borohydride Digest
And to the acyl azides of N-substituted, 6aminopenicilanic acids, to give the corresponding penicillanyl alcohols (8). It has been used in the synthesis of antidepressant aryloxyphenylpropylamines (9) and antigenic glycopeptides (10). Azide reductions with bis(triphenylphosphine) copper (1) borohydride (11) and with NaBH4 under phase transfer conditions (12,13) have also been reported. Alky and aromatic azides can be reduced to amines with transition metals and sodium borohydride under mild reaction conditions. (14,15, 16) Some of these reactions are also catalytic. Zinc borohydride formed in situ or complexed with DABCO can reduce alkyl and aromatic azides to amines in high yield. (17,18) Reaction of sodium borohydride with 1,3 dithiolethane forms a reactive species which will reduce azides easily.(19) Methanol is another reagent when added to a solution of sodium borohydride will reduce both aromatic and aliphatic azides. (20,21) Trifluoro actic acid with sodium borohydride will n-alkylate azide groups. (22) Borohydride exchange resin with and with out nickel acetate in methanol at RT will reduce aromatic
*For Online Consulting Only
press -F for Searching
83
and aliphatic azides to their corresponding primary amine in high yields. (23,24) References: 1) Boyer, J.H.; Ellzey, S.E. J. Org. Chem. 1958, 23, 127; Chem. Abstr. 52, 18276f 2) Smith, P.A.; Hall, J.H.; Kan, R.O. J. Am. Chem. Soc. 1962, 84, 485; Chem. Abstr. 56,14129g 3) Woodward, R.W. et. al. J. Med. Chem. 1970, 13, 979; Chem. Abstr. 73, 87769m 4) Verheyden, J.P.H.; Wanger, D.; Moffatt, J.G. J. Org. Chem. 1971, 36, 250; Chem. Abstr. 74, 54139y 5) Sztaricskai, F.; Pelyvas, I.; Bognar, R.; Tamas, J. Acta, Chim, Hung. 1983, 112, 275; Chem. Abst. 99, 2212852y 6) Kirk, D.N.; Wilson, M.A.; J. Chem. Soc. (C) 1971, 414; Chem. Abstr. 74, 112291e 7) Ehrart, G.; Siedel, W.; Nahm, H. Chem. Ber. 1957, 90, 2088; Chem. Abstr. 53, 276h 8) Perron, Y.G. et. al. J. Med. Chem. 1964, 7, 483; Chem. Abstr. 61, 5631a 9) U.S. 4,313,896 1982; Chem. Abstr. 96, 142447g 10) Ferrari, B.; Pavai, A.A. Tetrahedron 1985, 41, 1939; Chem. Abstr. 103, 160841y 11) Clarke, S.J.; Fleet, G.W.; Irving, E.WM. J. Chem. Res. (s) 1981, 17; Chem. Abstr. 94, 208452x
Rohm and Haas : the Sodium Borohydride Digest
12) Rolla, F. J. Org. Chem. 1982, 47, 4327; Chem. Abstr. 97, 161849b 13) Vlassa, M.; Kezdi, M. Pol. J. Chem. 1984, 58, 611; Chem. Abstr. 103, 87759w 14) Rao, H.S.P.; Siva, P. Synth. Commun. 1994, 24, 549 15) Rao, H.S.P.; Reddy, K.S.; Turnbull, K.; Borchers, V. Synth. Commun. 1992, 22, 1339 16) Tschaen, D.M.; Abramson, L.; Cai, D.; Desmond, R.; Dolling, U.H.; Frey, L.; Karadty, S.; Shi, Y.ZJ.; Verhoeven, T.R. J. Org. Chem. 1995, 60, 4324 17) Ranu, B.; Sarkar, A.; Chakraborty, R. J. Org. Chem. 1994, 59, 4114; Chem. Abstr. 121 82111 18) Firouzabadi, H.; Adibi, M.; Zeynizadeh, B. Synth. Commun. 1998, 28, 1257 19) Pei, Y.; Wickham, B.O.S. Tetrahedron Lett. 1993, 34, 7509 20) Soai, K.; Yokoyama, S.; Ookawa, A. Synthesis 1987, 48 21) Krein, D.M.; Sullivan, P.J.; Turnbull, K. Tetrahedron Lett. 1996, 7213 22) U.S. 5,012,000 1991 23) Yoon, N.M.; Choi, J.; Shon, Y.S. Synth. Commun. 1993, 23, 3047 24) Kabalka, G.W.; Wadgonkar, P.P.; Chatla, N. Synth. Commun. 1990, 20, 293
*For Online Consulting Only
press -F for Searching
84
Rohm and Haas : the Sodium Borohydride Digest
REDUCTIVE DEAMINATION The alkaline cleavage of compounds of the type RN(NO)ONH2 with NaBH4 has been reported (1) to give the hydrocarbon RH. The reaction proceeds via an intermediate cabonium ion, similar to dehalogenantion with NaBH4. In hexameylphosphoraide, N,N-disulfonimides of primary amines, e.g. RN(SO2C6H4Me-p)2 where R= decyl, or 2,5-Me2C4H3CH2 are reduced to the hydrocarbon RH by NaBH4 in good yield. Other deamination, e.g. of amidines (3), have been reported. References: 1) Kimse, W.; Shuette, H. Liegig, Ann. Chem. 1968, 718, 86; Chem. Abstr. 70, 36855s 2) Hutchns, R.O.; Cistone, F.; Goldsmith, B.; Heuman, P. J. Org. Chem. 1975, 40, 2018; Chem. Abstr. 83, 58333r 3) Okamoto, Y.; Kinoshita, T. Chem. Pharm. Bull 1981, 29, 1165; Chem. Abstr. 95, 97752u
*For Online Consulting Only
press -F for Searching
85
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest
DIAZONIUM SALTS NaBH4 has been reported to reduce diazonium fluoroborates in high yields (1,2) using either methanol or dimethylformamide as solvent. This is a reliable means of replacing diazonium groups by hydrogen, and thus of removing from aromatic rings groups easily converted to the diazonium salts, such as nitro, amino, and carbonyl groups.
R
N2+ BF4NaBH4
H R
The use of a solvent that does not interact with borohydride, such as higher alcohols, amines and glycol ethers, is preferred. Phenyldiimine (R-N=NH) has been suggested to be the intermediate in the NaBH4 reduction of benzenadiazonium salts, and under anaerobic conditions has been detected in this reaction (3,4) Diazonium groups can be reduced to their corresponding hydrazine efficiently with sodium borohydride or borohydride exchange resins. (5,6)
*For Online Consulting Only
86
References: 1) Hendrickson, J.B. J. Am. Chem. Soc. 1961, 83, 1251; Chem. Abstr. 55, 13345c 2) Xu, G; Shi, X; Liu, M. Lanzhou Daxue Xueao, Ziran Kexueban 1983, 19, 112; Chem. Abstr. 99, 21739g 3) Traylor, T.G.; McKenna, C.E. J. Am. Chem. Soc. 1971, 93, 2323; Chem. Abstr. 75, 5372f 4) Koenig, E.; Musso, H; Zahorszky, U.I. Angew Chem, Int. Ed. Engl. 1972, 11, 45; Chem. Abstr. 76, 85126h 5) Bandgar, B. P.; Thite, C. S. Synth. Commun. 1997, 27, 635-639; Chem. Abstr. 126211857 6) HU 50108, 1989; Chem. Abstr. 113 5904
Rohm and Haas : the Sodium Borohydride Digest
HETEROCYCLIC C=N BONDS Alembic: 7,12 Numerous examples of heterocyclic C=N reductions by NaBH4 have appeared in the literature in the last 20 years. NaBH4 has found wide application in this area, mainly because the work-up is much easier and the products are of high purity. NaBH4 selectively reduces the C=N bond in a number of heterocycles, such as 7-aminofurazone[3,4-d] pyrimidines (1).
87
press -F for Searching RO2C RO2C
CO2R
CO2R
NaBH4
N
N H CO2R
RO2C N H
Quinoxalines (3),
O N NH
N
N
N Ph
R
H N
NaBH4 AcOH, 5oC
R N H
O N
N
Pyracrimycin A (4),
3,5 substituted pyridines (2). H
N H
NaBH4
CONH2
N H
H H
CONH2
in which neither the C=C bond nor the amide group is reduced.
*For Online Consulting Only
88
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest
NaBH4 is also a versatile reagent for heterocyclic C=N bond reduction in alkaloid synthesis, e.g., in the synthesis of veracintine (5),
RO
RO N* HCl
RO
Me
NaBH4
OH
HO
N
RO
OH
HO
CO2Me
CO2Me
Me
N
Reserpine (7,8) and analogs (9-11), and dihydrovasicnone
Me
Me
Me
HO
Tetrahydroisoquiniline derivatives (6).
NaBH4
N
H
N N
N
Me
N H
O
O
NaBH4
HO
H
In which the either group is unreactive (12). Other areas of application also involve the synthesis of vitamins, e.g. pteridine derivatives (13,14) and tetrahydrofolic acid (15), O
H2N
O N
HN
Cl
N
N
N
HN
NaBH4 H2N
N
N H
*For Online Consulting Only
H
Cl
Rohm and Haas : the Sodium Borohydride Digest
Amino acids (16) HO HO
N
CO2H
H
and pyrines (17, 18) Recent applications include the conversion of pyrroline carboxylates to proline (19), the reduction of benzoxazepines (20), stereoselective synthesis of cis tetrahydropyrimidines (21) and N-norreticuline (22), and the formation of tetrahydrocarbolines (23) and dihydrondoloquinazolines (24). Sodium borohydride with carboxylic acid forms trialkoxyborohydrides which have been demonstrated to be a general method to chemoselectively reduce cyclic imines to cyclic amines. (25-36) Sodium borohydride with NiCl2 have also been used to reduce cyclic imine to their corresponding amines. (37)
*For Online Consulting Only
press -F for Searching
89
References: 1) Maki, Y. Chem. Pharm. Bull. 1976, 24, 234; Chem. Abstr. 84, 180161u 2) Booker, E.; Eisner, U. J. Chem. Soc., Perkin Trans 1 1975, 929; Chem. Abstr. 83, 79041j 3) Rao, K.V.; Jackman, D. J. Heterocycl. Chem. 1973, 10, 213; Chem. Abstr. 79, 18669r 4) Coronelli, C.; Vigevani, A.; Cavalleri, B.; Gallo, G.G. J. Antibiot. 1971, 24, 495; Chem. Abstr. 76, 140387a 5) Vassova, A Voticky, Z.; Tomko, J.; Ahond, A. Collect. Czech. Chem. Commun. 1976, 41, 2964; Chem. Abstr. 86, 90128a 6) Dornyei, G.; Szantay, C. Acta Chim. Acad. Sci. Hung. 1976, 89, 161; Chem. Abstr. 86, 29595j 7) Woodward, R.B. et. al. J. Am. Chem. Soc. 1956, 78, 2023; Chem. Abstr. 50, 13967b 8) Woodward, R.B. et. al. Tetrahedron, 1958, 2, 1; Chem. Abstr. 52, 11870f 9) Velluz, L. et. al. Bull. Soc. Chim. France 1958, 673; Chem. Abstr. 52, 18478d 10) Protiva, M.; Novak, L. Naturwiss. 1959, 46, 579; Chem. Abstr. 54, 6775I 11) Protiva, M.; Ernest, I. Naturwiss. 1960, 47, 156; Chem. Abstr. 54, 19746e
Rohm and Haas : the Sodium Borohydride Digest
12) Zharekeev, B.K.; Telezhenetskaya, M.V.; Khashimov, K.; Tunusov, S.Y. Khim, Prir. Soedin. 1974, 679; Chem. Abstr. 82, 73290x 13) Taylor, E.C.; Kobylecki, R. J. Org. Chem. 1978, 43, 680; Chem. Abstr. 88, 89628y 14) Pendergast, W.; Hall, W.R. J. Org. Chem. 1985, 50, 388; Chem. Abstr. 102, 78834u 15) Boyle, P.H.; Keating, M.T.; J. Chem. Soc. Chem. Commun. 1974, 375; Chem. Abstr. 81, 105452z 16) Ramaswamy, S.G.; Adams, E. J. Org. Chem. 1977, 42, 3440; Chem. Abstr. 87, 184925f 17) Maki, Y.; Suzuki, M.; Ozeki, K. Tetrahedron Lett. 1976, 1199; Chem. Abstr. 85, 94314j 18) Beisler,J.A.; Abbai, M.M.; Driscoll, J.S. U.S. Pat. Appl. 712, 854 (Aug. 8, 1976); Chem. Abstr. 87, 62862n 19) Smith, R.J. Enzyme 1984, 31, 115; Chem. Abstr. 101, 2755c 20) Levkovskaya, L.G.; Sazanov, N.V. et. al. Khim. Geterotsiki. Soedin. 1985, 122; Chem. Abstr. 103, 37460w 21) Cho, H.; Shima, K. et. al. J. Org. Chem. 1985, 50, 4227; Chem. Abstr. 103, 178228p 22) Hung. Teljes 30,591 1984; Chem. Abstr. 101, 152163x
*For Online Consulting Only
press -F for Searching
90
23) Nakamura, T.; Ishida, A.; Irie, K.; Oshishi, T. Chem. Pharm. Bull. 1984, 32, 2859; Chem. Abstr. 102, 6239 24) U.S.S.R. 816,116 1985; Chem. Abstr. 105, 208906u 25) Viagante, B.A.; Ozols, Y.Y.; Durbur, G. Y. Khim. Geter. Soed. 1991, 1680 26) Carling R.W.; Leeson, P.D.; Moseley, A.M.; Baker, R.; Foster, A.C.; Grimwood, S.; Kemp, J.A. Marshall, G.R. J. Med. Chem. 1992, 35, 1942 27) Brown, D.W.; Mahon, M.F.; Hihan, A.; Sainbury, M. J. Chem. Soc. Perkin Trans. 1 1995, 3117 28) Yadagiri, B.; Lown, J.W. Synth. Commun. 1990, 20, 175 29) Bock, M.G.; DiPardo, R.M.; Rittle, K.E.; Evans, B.E.; Freidinger, R.M.; Veber, D.F.; Chang, R.S.L.; Chen, T.; Keegen, M.E.; Lotti, V.J. J. Med.. Chem. 1986, 29, 1941 30) Ishii, H.; Ishikawa, T.; Ichikawas, Y.; Sakamoto, M.; Ishikawa, M.; Takahashi, T. Chem. Pharm. Bull. Jpn. 1984, 32, 2984 31) Uchida, M.; Chihiro, M.; Morita, S.; Yamashita, H.; Yamasaki, K.; Kanbe, T.; Yabuuchi, Y.; Nakagawa, K. Chem. Pharm. Bull Jpn. 1990, 38, 534 32) Bergman, J.; Tilstam, U.; Tonroos, K.W. J. Chem. Soc., Perkin Trans. 1 1987, 519 33) Moody, C.J.; Warrellow, G.J. Tetrahedron Lett. 1987, 28, 6089 34) Bleicher, L.S.; Cosford, N.D.P.; Herbaut, A.; McCallum, J.S.; McDonald, I.A. J. Org. Chem. 1998, 63, 1109
Rohm and Haas : the Sodium Borohydride Digest
35) Evans, B.E., et. al. J. Med. Chem. 1987, 30, 1229 36) Orito, K.; Miyazawa, M.; Kanbayashi, R.; Tokuda, M.; Suginome, H. J. Org. Chem. 1999, 64, 6583 37) Roberts, D.; Jopule, J.A.; Bos, M.A.; Alvarez, M. J. Org. Chem. 1997, 62, 568
*For Online Consulting Only
press -F for Searching
91
92
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest
HYDRAZONES Alembic 12 The reduction of hydrazones (R-CH=NNHR') to either hydrocarbon or hydrazides has been reported. (1-3) Tris 2,4-methanoprotoadamantane is synthesized by reducing the tosylhydrazone derivative in EtOH(4).
p-Tosyl hydrazone of conjugated olefinic or aromatic carbonyl compounds (e.g. carvone) undergo elimination reaction in preference to reduction with NaBH4, NaOR or K2CO3 in methanol to yield methyl ethers instead of hydrocarbon (11).
NNHTs
NaBH4
OMe
NaBH4 MeOH
N
NH
Ts
This has also been applied to the synthesis of 1-methyl1-dihalomethyl cyclohexane derivatives (5). A number of hydrazides have been prepared by The NaBH4 reduction of the hydrazones (6,9). hydrazones C=N bond is selectively reduced e.g. in the synthesis of 3,4,5-trimethxybenzol hydrazides (10) . MeO MeO
O N H
N
R
NaBH4
MeO
MeO R'
MeO
*For Online Consulting Only
O
H N H
MeO
N
R R'
H
The hydrocarbon can, however, be obtained by changing solvents (12). Recent applications include the synthesis of phoracatholide (13) and steroid derivatives (14,15) and the labeling of glycoproteins (16). Zinc cyanoborohydride can reduce hydrazones to hydrocarbons in high yields. (17,18) A mechanistic study on the reductive pathway of cyanoborohydride has been completed. (19) Bis-triphenyl phosphine copper (I) borohydride can reduce hydrazones to alkanes in high yields.(20) Sodium
Rohm and Haas : the Sodium Borohydride Digest
borohydride in the presence of CeCl3 in MeOH at RT will also reduce hydrazones to alkanes in high yield. (21) Acetoxy borohydrides have also been demonstrated to reduce hydroazones to alkanes (22) References: 1) Kabalka, G.W.; Baker, J.D. J. Org. Chem. 1975, 40, 1834 2) Kabalka, G.W.; Summer, S.T. J. Org. Chem. 1981, 46, 1217 3) Eycken, E.V.D.; Wilde, H.D.; Deprez, L.; Wandewalle, M. Tetrahedron Lett. 1987, 28, 4759 4) Sasaki T.; Eguchi, S.; Hirako, Y. J. Org. Chem. 1977, 42, 2981; Chem. Abstr. 87, 117621r 5) Wenkert, E.; Wovkulick, P.; Pellicciari, P.; Ceccherelli, P. J. Org. Chem. 1977, 42, 1105; Chem. Abtr. 86, 120829z 6) Claudi, F.; Grifantini, M.; Guilni, U.; Martelli, S.; Natalini, P.J. Pharm. Sci. 1977, 66, 1355; Chem. Abstr. 87, 167827h 7) Mazone, G.; Arrigo-Reina, R.; Amico-Roxas, M. Farmaco, E.D. Sci. 1976, 31, 517; Chem. Abstr. 85, 142768k 8) Ger. Offen. 2,305,972 1973; Chem. Abstr. 79, 115602w
*For Online Consulting Only
press -F for Searching
93
9) Vartanyan, S.A.; Vartanyan, R.S. et. al. Khim. Farm. Zh. 1985, 19, 821; Chem. Abstr. 105, 42705a 10) Mazzone, G.; Arrigo, R.R. Boll. Sedute Accad. Gioenia Sci. Natur. Catania 1971, 41, 1755; Chem. Abstr. 78, 15733a 11) Grandi, R.; Marchesini, A.; Pagnonic, U.M.; Trave, R. J. Org. Chem. 1976, 41, 1755; Chem. Abstr. 84, 180401x 12) Silvestri, M.G.; Bednarski, P.J.; Kho, E. J. Org. Chem. 1985, 50, 2798; Chem. Abstr. 103, 54313t 13) Mahanjan, R.J.; DeAraujo, H.C. Synthesis 1981, 46, 2786; Chem. Abstr. 94, 208686b 14) Iida, T.; Chang, F.C. J. Org. Chem. 1981, 46, 2786; Chem. Abstr. 95, 25399m 15) Iida, T.; Tamura, R.; Matumoto, T.; Chang, F.C. Synthesis 1984, 957; Chem. Abstr. 102, 221092h 16) Estep, T.N.; Miller, T.J. Anal. Biochem. 1985, 157, 100; Chem. Abstr. 105, 168335y 17) Kim, S.; Oh, C.H.; Ko, J.S.; Ahn, K.H.; Kim, Y.J. J. Org. Chem. 1985, 50, 1927 18) Paquette, L.A.; Wang, T.Z.; Vo, N.H. J. Am. Chem. Soc. 1993, 115, 1677 19) Miller, V.P.; Yang, D.Y.; Weigel, T.M.; Han, O.; Liu, H.W. J. Org. Chem. 1989, 54, 4175 20) Fleet, G.W.J.; Harding, P.J.C. Tetrahedron Letter. 1980, 4031
Rohm and Haas : the Sodium Borohydride Digest
21) Fleet, G.W.J.; Harding, P.J.C.; Whitcombe, M.J. Tetrahedron Lett. 1980, 21, 4031 22) Maryanoff, B.E.; McComsey, D.F.; Nortey, S.O. J. Org. Chem. 1981, 46, 255
*For Online Consulting Only
press -F for Searching
94
95
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest
IMINES Alembic 23, 33, 43, 62
NH2 H
R
NaBH4 readily reduces imines to their corresponding secondary amines in good yield under mild condition (1-6).
O
+
O
H
N
NO2 NaBH 4 N
R
AcOH
Me
H
R
N
HO
NO2
Me
Me
Allylic imines have been reduced to allylic amines in high yield with sodium borohydride.(7,8) A large number of Schiff bases have also been reduced to the amine utilizing NaBH4 (9-12). R
R CO2H N
R' H C
CO2H H
NaBH4
R"
N H
H
R' R"
This type of reduction has been shown to provide the most sensitive method of determining amino acids (13) The amino acids are condensed with pyridoxal under alkaline condition to form the Schiff base,
*For Online Consulting Only
OH OH
OH Me
H
O
H HO
Cl
Cl
R
N
N
which is then reduced to the pyridoxylamino acid with sodium borohydride. The individual acids are separated by column chromatography, followed by radiochemical determination. In this way, quantities of amino acids as small as 10-12 mmol can be detected. The selective reduction of imines has made NaBH4 a versatile reagent n the synthesis of antibacterial such as alkylaminoerythromycins (14), fungicides (15), 8aminogibbanes (16), N-alkyamino pivalates (17) and antiinflammatory hydroxybenzylamines (18). Sodium cyanoborohydride is also used frequently for imine reductions (19-23). Zinc borohydride can reduce imines to secondary amines in high yields (24-26)
Rohm and Haas : the Sodium Borohydride Digest
Triacetoxy borohydride have been shown to reduce imines formed from the reductive amination of aldehydes and ketones with amines.(27) Stereospecific reduction of imines has been reported (28-30), including the chiral synthesis of doxpicomine (31), in which an imine is reduced with 88% enantiomeric excess. Sodium borohydride with amino acids have been shown to steroselctively reduce imines in high ee.(32) Stereoselctive reduction of imines can be accomplished catalytically with a cobalt catalyst. (33) Zinc borohydride can also reduce imines steroselectively.(34) References: 1) Haire, M.J. J. Org. Chem. 1977, 42, 3446; Chem. Abstr. 87, 183524n 2) Zhang, Z.; Martell, A.E.; Motekataitis, R.J.; Fu, L. Tetrahedron. Lett. 1999, 40, 4615 3) Effenberger, F.; Jager, J. J. Org. Chem. 1997, 62, 3867 4) Froelich, O,.; Desos, P.; Bonin, M.; Quirion, J.C.; Hussan, H.P J. Org. Chem. 1996, 61, 6700 5) Roberts, D.; Jopule, J.A.; Bos, M.A.; Alvarez, M. J. Org. Chem. 1997, 62, 568 6) Krepski, L.R.; Jensen, K.M.; Heilmann, S.M.; Rasmussen, J.K. Synthesis 1986, 301
*For Online Consulting Only
press -F for Searching
96
7) Shin, W.S.; Lee, K.; Oh, D.Y. Tetrahedron Lett. 1995, 36, 281 8) De Kimpe, N.; Stanoeva, E.; Verhe, R.; Schamp, N. Synthesis 1988, 587 9) Lakhani, B.B.; Merchant, J.R. J. Inst. Chem. 1977, 49, 172; Chem. Abstr. 87, 167668g 10) Ger. Offen. 3,034,664 1982; Chem. Abstr. 97, 55815c 11) U.S. 4,454,226 1984; Chem. Abstr. 101, 70879w 12) Merrettt, M.; Stammers, D.K.; White, R.D.; Wootton, R.; Kneen, G. Biochem. J. 1986, 239, 387; Chem. Abstr. 105, 218622n 13) Lustenberger, N.; Lange, H.; Hempel, K. Angew. Chem. Int. Ed. Engl. 1972, 11, 227; Chem. Abstr. 76, 148553x 14) Ger. Offen 2,606,662 1977; Chem. Abstr. 88, 23335u 15) Eur. Pat. Appl. 129,433 1984; Chem. Abstr. 103,6367s 16) Hung, P.D.; Adam, G.J. Prakt. Chem. 1984, 326, 253; Chem. Abstr. 101, 38694w 17) Coatwes, R.M.; Cummins, C.H. J. Org. Chem. 1986, 51, 1383; Chem. Abstr. 104, 186037m 18) U.S. 4,578,290 1986; Chem. Abstr. 105, 97344n 19) Oveman, L.E.; Mendelson, L.T.; Jacobsen, E.J. J. Am. Chem. Soc. 1983, 105, 6629; Chem. Abstr. 99, 176116a 20) Borne, R.F.; Fifer, E.K.; Waters, I.W. J. Med. Chem. 1984, 27, 1271; Chem. Abstr. 101, 1306113s 21) W.S. 4,537,885 1985; Chem. Abstr. 104, 155969n 22) S. Aferican 83 08,227 1985; Chem. Abstr. 105, 114934z
Rohm and Haas : the Sodium Borohydride Digest
23) Cox, E.D.; Hamaker, L.K.; Li, J.; Yu, P.; Czerwinski, K.M.; Deng, L.; Bennett, D.W.; Cook, J.M.; Watson, W.H.; Krawiec, M. J. Org. Chem. 1997, 62, 44 24) Ranu, B.C.; Sarkar, A.; Majee, A. J. Org. Chem. 1997, 62, 1841 25) Uneyama, K.; Hao, J.A.; Amii, H. Tetrahedron Lett. 1998, 39, 4079 26) Kotsuki, H.; Yoshimura, N.; Kadota, I.; Ushio, Y.; Ochi, M. Synlett, 1990, 401 27) Ryglowski, A.; Kafarski, P. Tetrahedron 1996, 52, 10685 28) Wrobel, J.E.; Ganem, B. Tetrahedron Lett. 1981, 22, 3447; Chem. Abstr. 96, 51861w 29) Czarnocki, Z; Mieczko, J.B. Pol. J. Chem. 1995, 69, 1447; Chem. Abstr. 124 9059 30) Zhu, J.Z.; Quirion, J.C.; Husson, H.P. Tetrahedron Lett. 1989, 30, 5137 31) Farkas, E.; Sunman, C.J. J. Org. Chem. 1985, 50, 1110; Chem. Abstr. 102, 149194y 32) Hajipour, A.R.; Hantehzadeh, M. J. Org. Chem. 1999 64, 8475 33) Sugi, K.D.; Nagata, T.; Yamamda, T.; Mukaiyama, T. Chem. Lett. 1997, 493
*For Online Consulting Only
press -F for Searching
97
34) Jackson, W.R.; Jacobs, H.A.; Matthews, B.R.; Jayatilake, G.S.; Watson, K.G. Tetrahedron. Lett. 1990, 31, 1447
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest
NITRILES Alembic 50, 55, 60 Examples of nitrile reduction by NaBH4 are limited to few heterocyclic compounds in which the – CN groups are activated by the heteroatom ring, e.g., the indole derivative (1) and some pyridine, quinoline (2) and napthalene (3) derivatives. Ph
H
Ph C
H
N NH2
NaBH4 N H
N H
Recently, NaBH4 has been reported to reduce effectively a number of aromatic nitriles to the amines in the presence of trifluoroacetic acid (4,5). The active species is believed to be sodium trifluoroacetoxyborohydride, was first formed by reacting an equimolar CF3COOH with NaBH4 in THF for 10 mins at 20 oC. In a series of studies involving nitrogenase reactions, Schrauzer has reported the NaBH4 reduction of isocyanide (6) and cyanides (7), catalyzed by
*For Online Consulting Only
98
molybdenum complexes, to the amines and a number of other products. The CN groups are activated by coordinating to a metal atom rendering the carbon center more electropositive and therefore, more easily attacked by BH4-. Similarly, perfuoroalkylnitirle are reduced to the amines (8). In the presence of a catalyst, e.g. Raney nickel, nickel or cobalt boride the nitrile groups can be effectively reduced, and this approach has found extensive applications in the reduction of aromatic nitrile compounds (9), alkaloids (10), amino acids and their derivatives (11), and biogenic polyamines derivatives (12). The combination of CoCl2 and sodium borohydride produces a reductive system that converts nitriles to either alkanes or amines.(13,14) Reaction of nitrile groups with girngard reagents to form imine groups, which are subsequently selectively reduced with zinc borohydride or sodium borohydride with trimethyl silane chloride have been demonstrated.(15,16) Lithium or sodium borohydride with trimethylsilane chloride have reduced nitrile groups to amines in high yields.(17) Borohydride exchange resin spiked with copper sulfate in MeOH at RT can reduce aromatic and aliphatic nitriles to their corresponding amines.(18) Lithium borohydride in a solvent mixture of MeOH and diglyme has demonstrated the same reactivity but at only moderate yields of the desired amine.(19)
Rohm and Haas : the Sodium Borohydride Digest
Nitriles can be removed as a cyanide group to leave an alkane group by using sodium borohydride or cyanoborohydride in low molecular weight alcohols at both RT and at elevated temperatures.(20-26) zinc borohydride has also shown similar reactively towards nitrile groups.(27) Publications include a patent on selective nitrile reduction (28), and a proposed mechanism and optimized procedure for cobalt boride catalyzed nitrile reduction have been reported. (29). References: 1) Rusinova, V.N. et. al. Khim. Geterotsikl. Soedin. 1974, 211; Chem. Abstr. 81, 37455a 2) Kikugawa, Y.; Kuramoto, M.; Saito, I.; Yamada, S. Chem. Pharm. Bull. 1973, 21, 1927; Chem. Abstr. 79, 145754q 3) Jpn. Kokai Tokkyo Koho 85, 100,542 1985; Chem. Abstr. 103, 123196w 4) Umino, N.; Iwaakuma, T.; Itoh, N. Tetrahedron Lett. 1976, 2875; Chem. Abstr. 86, 16375m 5) Beugelmans, R.; Singh, .P.; Bois-Choussy, M.; Chastanet, J.; Zhu, J. J. Org. Chem. 1994, 59, 5535 6) Schrauzer, G.N.; Doemeny, R.A.; Kiefer, G.W.; Frazier,R.H. J. Am. Chem. Soc. 1972, 94, 3604; Chem. Abstr. 77, 15965g
*For Online Consulting Only
press -F for Searching
99
7) Schrauzer, G.N.; Doemeny, R.A.; Kiefer, G.W.; Frazier,R.H. J. Am. Chem. Soc. 1972, 94, 7378; Chem. Abstr. 77, 161531d 8) Ellzey, S.E.; Wittman, J.S.; Connick, W.J. J. Org. Chem. 1965, 30, 3945; Chem. Abstr. 64, 6490b 9) Wade, R.C.; Holah, .G.; Hughes, A.N.; Hui, B.C. Catal. Rev. Sci. Eng. 1976, 14, 211; Chem. Abstr. 86, 22275w 10) Harayama, T.; Ohtani, M.; Oki, M.; Inubushi, Y. Chem. Pharm. Bull. 1975, 23, 1511; Chem. Abstr. 83, 131793x 11) Mezo, I.; Havanek, M.; Tepan, I.; Benes, J.; Tanaces, B. Acta. Chim. Acas. Sci. Hung. 1975, 23, 1511; Chem. Abstr. 83, 59244z 12) Ger. Offen. 3,506,330 1985; Chem. Abstr. 104, 168275h 13) Williams, J.P.; Laurewnt, D.R.; Friedrich, D.; Pinard, E.; Roden, B.A.; Paquette, L.A. J. Am. Chem. Soc. 1994, 116, 4689 14) Backvall, J.E.; Plobeck, N.A. J. Org. Chem. 1990, 55, 4528 15) Kotsuki, H.; Yoshimura, N.; Kadota, I.; Ushio, Y.; Ochi, M. Synthesis 1990, 401 16) Urabe, H.; Aoyama, Y.; Sato, F. J. Org. Chem. 1992, 57, 5056 17) Giannis, A.; Snadhoff, K. Angew. Chem. Int. Ed. Engl. 1989, 28, 218 18) Sim, T.B.; Yoon, N.M. Bull. Chem. Soc. Jpn. 1997, 70, 1101
Rohm and Haas : the Sodium Borohydride Digest
19) 20) 21) 22) 23) 24) 25) 26) 27) 28) 29)
Soai, K.; Ookawa, A. J. Org. Chem. 1986, 51, 4000 Mitch, C.H. Tetrahedron Lett. 1988, 29, 6831 Hui, B.C Inorg. Chem. 1980, 19, 3185 Guerrier, L.; Royer, J.; Grierson, D.S.; Husson, H.P. J. Am. Chem. Soc. 1983, 105, 7754 Yue, C.; Royer, J.; .; Husson, H.P. J. Org. Chem. 1990, 55, 1140 Grierson, D.S.; Royer, J.; Gruerrier, L.; Husson, H.P. J. Org. Chem. 1986, 51, 4475 Marco, J.L.; Royer, J.; Husson, H.P. Synth. Commun. 1987, 17, 669 Polniaszek, R.P.; Belmont, S.E. J. Org. Chem. 1990, 55, 4688 Vidal, L.; Royer, J.; Husson, H.P. Tetrahedron Lett. 1995, 36, 2991 PCT Int. Appl. 85, 00,605 1985; Chem. Abstr. 104, 110018k Osby, J.O.; Heinzman, S.W.; Ganem, B. J. Am. Chem. Soc. 1986, 108, 67; Chem. Abstr. 104, 50458s
*For Online Consulting Only
press -F for Searching
100
Rohm and Haas : the Sodium Borohydride Digest
NITRO COMPOUNDS Alembic: 4, 6, 9, 48, 51, 52, 61 Under normal conditions, NaBH4 does not reduce the nitro group, except in a few aromatic nitro compounds. For example, nitroanthraquinones are reduced to the corresponding amines in 65 to 100 % yield (1) in H2O, alcohols, aqueous DMF and THF. Reduction to the amine has also been reported for the 2carbenthoxyindole derivatives (2). Ordinarily, aliphatic nitro compounds are not reactive with NaBH4, and the reduction of nitrobenzene generally results in a number of products, e.g. azo, azoxy, hydrazo derivatives and aniline (3,4). In the presence of thiols, NaBH4 reduces nitro groups to amine, hydroxylamines, azo and azoxy compounds, and the activity is attributed to the thiolate derivatives (5). A number of transition metal complexes have been reported to catalyze the borohydride reduction of nitro compounds, e.g., PdCl2(N-methylpyrrolidinone)2 (6), K2Ni(CN)4 (7), NiX2P2(8), and Co(NH3)6 3+ (9), MoO3 (10). NaBH4 can also convert a number of aromatic nitro compounds to the amines in the presence of palladium on charcoal (11-16). Cobalt and nickel borides, generated from Co(II) and Ni(II) salts and
*For Online Consulting Only
press -F for Searching
101
NaBH4 are extremely effective in catalyzing the reduction of nitro compounds to amines (17-20). It has been reported that copper (I) acetate will reduce aromatic nitro compounds in ethanol. (21) Other copper (I) complex such as CuBr•SMe2 in methanol at RT have also been demonstrated to reduce aromatic nitro compounds in the presence of halides, alkoxides and amines. (22) Potassium borohydride with CuCl will reduce aromatic nitro compounds to amines at RT. (23) Aromatic nitro groups can also be selectively reduced to amino compounds by sulfurated sodium borohydride, NaBH2S3, prepared by the reaction between sulfur and NaBH4 in dry THF (24,25) Sato has found (26) that SnCl2•2 H2O and NaBH4 in ethanol reduces aromatic nitro compounds selectively in the presence of other functional groups, such as ester, chloro, nitrile and olefinic bonds. Bismuth trichloride or SbCl3 with either sodium or potassium borohydride will reduce both aromatic and aliphatic nitro compounds to their corresponding amine in the presence of nitrile, chloride amine, hydroxy and alkoxy groups at elevated temperatures.( 27,28,29,30) The use of bismuth trichloride as a catalytic crosscoupling reagent of two aromatic nitro molecules to a azobenzene compound at RT has been demonstrated. This reaction will not effect ester, nitrile, chloride, hydroxy and alkoxy groups. (31)
Rohm and Haas : the Sodium Borohydride Digest
The addition of selenium metal to sodium borohydride to form a Lancette type reagent that reduces aromatic nitro compounds to aromatic amines. (32) Sodium borohydride with catalytic amounts of sodium methoxide will reduce nitro groups on imidazoles, pyrazoles or pyridine rings at RT. (33) α−β unsaturated nitroalkenes can be reduced to a ketone group with NaBH4 and hydrogen peroxide at RT. Under these reaction conditions will not effect acetal, ester or olefinic groups. (34) Sodium borohydride with ammonium sulfate in ethanol will reduce aromatic nitro compounds in less then an hour. This methodology is chemoselective and will not reduce nitrile, ester, carboxylic acid, halide and olefinic groups. (35 ) Borohydride exchange resins spiked with Ni acetate will reduce aliphatic and aromatic nitro compounds at RT in MeOH. (36) The nickel complexes anchored to a polymer backbone with NaBH4 can reduce nitrobenzene to analine. (37). It has been demonstrated that sodium borohydride in refluxing diglyme can reduce nitrobenzene to analine in quantitative yields if
*For Online Consulting Only
press -F for Searching
102
ammonium chloride is added to the reaction as a proton donor.(38) References: 1) Morley, J.O. Synthesis 1976, 8, 528; Chem. Abstr. 85, 177120v 2) Nantko-Namirski, P.; Ozdowska, Z. Acta Pol Pharm. 1975, 32, 273; Chem. Abstr. 84, 17065g 3) Panson, G.S.; Weill, C.E. J. Org. Chem. 1956, 21, 803; Chem. Abstr. 51, 7320a 4) Nose, A.; Kudo, T. Yakugaku Zasshi 1977, 97, 116; Chem. Abstr. 86, 170979u 5) Maki, Y.; Sugiyama, H.; Kikucki, K.; Seto, S. Chem. Lett. 1975, 1093; Chem. Abstr. 83, 192711r 6) Nazarova, N.M.; Opyttsev, Y.A.; Shcherbakova, S.I.; Freidlin, L. K. Izv. Akad. Nauk SSSR, Ser. Khim. 1975, 2589; Chem. Abstr. 84, 43501r 7) Hanaya, K.; Kudo, H.; Hara, T.; Fujita, N.; Iwase, A. Yamagata Daigaku Kiyo Shizen Kagaku 1974, 8, 397; Chem. Abstr. 81, 169229q 8) Hanaaya, K.; Fujita, N.; Kudoi, H. Chem. Ind. 1973, 794; Chem. Abstr. 79, 125994q 9) Arai, Y. et. al. Nippon Kagaku Kaishi 1972, 194; Chem. Abstr. 76, 85484c 10) Yanada, K.; Yanada, R.; Meguri, H. Tetrahedron Lett. 1992, 1463
Rohm and Haas : the Sodium Borohydride Digest
11) Neilson, T.; Wood, H.C.S.; Wylie, A.G. J. Chem. Soc. 1962, 371; Chem. Abstr. 56, 15391b 12) Hahn, R.C.; Johnson, R.P. J. Am. Chem. Soc. 1977, 99, 1508; Chem. Abstr. 86, 170495h 13) Billing, M.J.; Baker, E.W. Chem. Ind. 1969, 654; Chem. Abstr. 71, 22123k 14) Coutts, R.T.; El-Hawari, A.M. Can. J. Chem. 1975, 53, 3637; Chem. Absrt. 84, 105464s 15) Numazawa, M.;Kimura, K. Steriods 1983, 41, 675; Chem. Abstr. 100, 68583f 16) Walker, T.E.; Matheny, C.; Storm, C.B.; Hayden, H. J. Org. Chem. 1986, 51, 1175; Chem. Abstr. 104, 168804e 17) Wade, R.C.; Holah, D.G.; Hughes, A.N.; Hui, B.C. Catal. Rev. Sci. Eng. 1976, 14, 211; Chem. Abstr. 86, 22275w 18) Nose, A.; Kudo, T. Chem. Pharm. Bull. 1981, 29, 1159; Chem. Abstr. 95, 132421j 19) Ger. Offen. 3,309,493 1984; Chem. Abstr. 102, 95892d 20) Osby, J.O.; Ganem, B. Tetrahedron Lett. 1986, 27, 1205; Chem. Abstr. 105, 23917e 21) Drouin, J.; Gauthier, S.; Patricola, O.; Lanteri, P.; Longeray, R. Synlett 1993, 791 22) Patel, H.V.; Vayas, K.A. Org. Prep. Proc. Int. 1995, 27, 81
*For Online Consulting Only
press -F for Searching
103
23) He, Y.; Zhao, H.; Pan, X.; Wang, S. Synth. Commun. 1989, 19, 3047 24) Lalancette, J.M.; Brindle, J.R. Can. J. Chem. 1971, 49, Chem. Abstr. 151488q 25) Jpn. Kokai Tokkyo Koho 85, 152, 497 1985; Chem. Abstr. 104, 69119d 26) Satoh, T.; Mitsuo, N.; Nishiki, M; Inoue, Y.; Ooi, Y. Chem. Pharm. Bull. 1981, 29, 1443; Chem. Abstr. 95, 97224y 27) Ren, P.; Pan, S.F.; Dong, T.W.; Wu, S.H. Chin. Chem. Lett. 1995, 6, 553; Chem. Abstr 123 313453 28) Ren, P.; Pan, S.F.; Dong, T.W.; Wu, S.H. Synth. Commun. 1995, 25, 3799 29) Borah, H.N.; Prajapati, D.; Sandhu, J.S. J. Chem. Res. (s) 1994, 228 30) Pan, S.F.; Ren, P.D.; Dong, T.W. Chinese Chem. Lett. 1996, 7, 981 31) Ren, P.; Pan, S.; Dong, T.; Wu, S. Synth. Commun. 1996, 26, 3903 32) Shao, J.G.; Wang, L.C.; Zheng, M.; Zhong, Q. Chinese Chem Lett. 1997, 8, 683 33) Suwinski, J.; Wagner, P.; Holt, E.M. Tetrahedron 1996, 52, 9541 34) Ballini, R.; Bosica, G. Synthesis 1994, 723 35) Gohain, S.; Prajapati, D.; Sandhu, J.S. Chem. Lett. 1995, 72
Rohm and Haas : the Sodium Borohydride Digest
36) Yoon, N.M.; Choi, J. Synlett 1993, 135 37) Loubinoux, B.; Chanot, J.J.; Caubere, P. J. Organomet. Chem. 1975, 88, C4; Chem. Abstr. 83, 27763b 38) Yang, C.M.; Pittman, Jr. C.U. Synth. Commun. 1998, 28, 2027
*For Online Consulting Only
press -F for Searching
104
NaBH4
The conversion of the nitroso group to the hydroxylamine has been reported with NaBH4 in the absence of a catalyst (1).
N OH
Transition metal complexes also catalyze the reduction, e.g. bis(dimethylglyoximato)cobalt(2), or palladium on charcoal (3,4). O N
N
N
N
47 %
NaBH4 NO Co(DMGH)2 NH2
*For Online Consulting Only
Pd/C NO
NaBH4
H
NMe2
NMe2
NITROSO COMPOUNDS
ON
105
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest
41 % 12 %
NH2
Nitroso reduction to the corresponding amine has been reported in the case of the anticancer drug methyl CCNU, in which a nitrourea is reduced to a semicarbazide by NaBH4 (5). The reduction of nitrosamine Æ amine can be accomplished in high yields using borohydride exchange resins spiked with CuI- sulfate in methanol at 0oC. (6) References: 1) Patrick, T.B.; Schield, J.A.; Kirchner, D.G. J. Org. Chem. 1974, 39, 1758; Chem. Abstr. 81, 25235r 2) Green, M.; Swinden, G. Inorg. Chim. Acta. 1971, 5, 49; Chem. Abstr. 75, 34882c 3) Neilson, T.; Wood, H.C.S.; Wylie, A.G. J. Chem. Soc. 1962, 371; Chem. Abstr. 56, 15391b 4) Goodman, M.M.; Knapp, F.F. J. Org. Chem. 1982, 47, 3004; Chem. Abstr. 97, 38614u 5) Caddy, B.; Idowu, O.R. Analyst 1982, 107, 550; Chem. Abstr. 97, 103741z
Rohm and Haas : the Sodium Borohydride Digest
6) Lee, S.Y.; Sim, T.B.; Yoon, N.M. Bull. Korean Chem. Soc. 1997, 18, 1127
*For Online Consulting Only
press -F for Searching
106
OXIMES Alembic 8, 50 The reduction of oximes may give amines, hydroxylamines or alcohols. Thus, ketoximes are reduced to the primary amines (1). O N
R
OH
OH NaBH4
Me
H N H
R
S
NOH
S
NHBz HO S NaBH4
OH
NHBz
S
OH
*For Online Consulting Only
O
NaBH4
N
R' R"CO2H
N
OH O
OH
OH
Me
NHBz
Partial reduction of an oxime may also afford a hydroxylamine; this can be achieved effectively by using NaBH4 in carboxylic acid (4).
R
Reductive hydrolysis of oximes generally produces the corresponding alcohols (2,3). NHBz HO
107
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest
HO R HO
NaBH4
N
R" R'
N
R"
R"CO2H
The reaction appears to be general for aldoximes and ketoximes, except for bezophenone oxime and bibenzyl ketoxime, among a number of compounds studied. An interesting report shows that NaBH4 absorbed on Al2O3 or silica gel effectively reduces oximes to hydroxylamines in benzene (5). Sulfurated sodium borohydride, NaBH2S3 (6-8) and NaBH4 in the presence of NiCl2 or MoO3 (9) have been used to reduce oximes to the amine. Sodium cyanoborohydride is often used to reduce oximes to hydroxylamines (10-12).
Rohm and Haas : the Sodium Borohydride Digest
Borohydride exchange resins spiked with nickel acetate have reduced aromatic oximes to amines in MeOH at RT. (13) Borane produced by the reaction of sodium borohydride with I2 or H2SO4 in THF at 0o C to reduce o-acyl oximes to amines. (14,15) Metal complexes such as ZrCl4, FeCl3 and SnCl4 have been shown to reduce asymmetric o-oximes to amines in high yields under mild reaction conditions. (16,17) Lithium borohydride as been shown to reduce oximes to hydroxy amines at RT in THF. (18) While amino oximes have been reduced to amino nitriles in refluxing acetonitrile. (19) References: 1) Seelkopt, C. Rev. Fac. Farm. Univ. Los Andes 1974, 15, 157; Chem. Abstr. 83, 78998q 2) Mikhno, S.D.; et. al. Zh. Org. Khim. 1977, 13, 175; Chem. Abstr. 86, 171291a 3) Nazir, M.; Kreiser, W.; Inhoffen, H.H. Synthesis 1977, 466; Chem. Abstr. 87, 133228y 4) Gribble, G.W.; Leiby, R.W.; Sheehan, M.N. Synthesis 1977, 856; Chem. Abstr. 88, 89018z 5) Ciurdaru, V.; Hodosan, F. Rev. Roum. Chim. 1977, 22, 1027; Chem. Abstr. 87, 201881h
*For Online Consulting Only
press -F for Searching
108
6) Lalancette, J.M.; Brindle, J.R. Can. J. Chem. 1970, 48, 735; Chem. Abstr. 72, 110402b 7) Jpn. Kokai Tokkyo Koho 79 119,485 1979; Chem. Abstr. 92, 128979t 8) Jpn. Kokai Tokkyo Koho 81, 122,386 1981; Chem. Abstr. 96, 122832a 9) Ipaktschi, J. Chem. Ber. 1984, 117, 856; Chem. Abstr. 101, 22611f 10) Baldwin, J.WE.; Kruse, L.I.; Cha, J.K. J. Am. Chem. Soc. 1981, 103, 942; Chem. Abstr. 94, 121385d 11) U.S. 4,312,887 1982; Chem. Abstr. 96, 142446f 12) Tsuchiya, T.; Nakano, M.; Torii, T.; Suzuki, Y.; Umezawa, S. Carbohydrate. Res. 1985, 136, 195; Chem. Abstr. 103, 123834c 13) Badgar, B.P.; Nikat, S.M.; Wadgaonkar, P.P. Synth. Commun. 1995, 25, 863 14) Barby, D.; Champagne, P. Synth. Commun. 1995, 25, 3503 15) U.S. 5,200,561 1993 16) Itsuno, S.; Sakurai, Y.; Shimizu, K.; Ito, K. J. Chem. Soc., Perkin Trans. 1 1990, 1859 17) Itsuno, S.; Sakurai, Y.; Shimizu, K.; Ito, K. J. Chem. Soc., Perkin Trans. 1 1989, 1548 18) Cho, B.T.; Seong, S.Y. Bull. Korean Chem. Soc. 1988, 9, 322
Rohm and Haas : the Sodium Borohydride Digest
19) Petukhov, P.A.; Tkachev, A.V. Tetrahedron 1997, 53, 2535
*For Online Consulting Only
press -F for Searching
109
Rohm and Haas : the Sodium Borohydride Digest
QUATERNARY COMPOUNDS Alembic: 15, 28 A wide variety of cyclic quaternary ammonium salts containing >C=N+< unsaturations have been reduced with NaBH4, including pyridinum (1-7) pyrazinium (8,9), pyrazolium (10,11), isoquinolinium (12,13,14), quinolium (15,16), pyroliumum (17), Pyoladine (18), oxazolium(19,20,21), thiazolium (22,23), and indoloquinolizium (24,25) in these the >C=N+< is effectively hydrogenated to the amine. One of the most interesting reactions of this type is the complete reduction of quaternized 4-aminopyridines to the 4-aminopiperidines (26), and the reduction of oxidopyrazinium iodides to 1-hydroxypiperazines (8),
OH
O N
Me
Me N+
N
Me
Me
Similar results are reported for ternary oxonium salts, e.g., substituted are reported for tenary oxonium salts, e.g. 2substituted 1,3-benzoathiolylium salts (27), and pyrylium salts (28,29).
R R NaBH4
N+
N
R
R
a reduction impossible to carry out by catalytic hydrogenantion.
*For Online Consulting Only
O O +
NaBH4
N
NaBH4
NH2
NH2
110
press -F for Searching
R'
R' R
O
R'
Thiopyrylium salts (solfonium compounds) (30) are reduced in a similar manner.
Rohm and Haas : the Sodium Borohydride Digest
NO2
S
S + NaBH4
S
NO2
S
Even nitrilium salts (-C+N-R), by way of imino ester [C(OR’)=N-R], are reduced in good yield to the secondary amine (31). Iminium salts have been reduced stereoselectively with sodium borohydride. (32,33,34) Trimethyl propogyl ammonium iodide can be reduced with sodium borohydride to an alkene and isopropyl alcohol in high yield (35) Nickel (II) chloride with sodium borohydride can reduce quartarnary ammonium salts in high yields (36).
*For Online Consulting Only
press -F for Searching
111
Alkaloids have been synthesized by reducing quarternary ammonium salts with sodium borohydride. (37) References: 1) Knaus, E.E.; Redda, K. J. Heterocycl. Chem. 1976, 13, 1237; Chem. Abstr. 86, 155471d 2) Boulton, A.J.; Epsztajn, J.; Katritzky A.R.; Nie, P. Tetrahedron Lett. 1976, 2689; Chem. Abstr. 86, 55248t 3) Lyle, R.E.; Krueger, W.E; Gunn, V.E. J. Org. Chem. 1983, 48, 3574; Chem. Abstr. 99, 139723a 4) Gessner, W.; Brossi, A.; Chen, R.S.; Fritz, R.R.; Abell, C.W. Helv. Chim. Acta 1984, 67, 2037; Chem. Abstr. 102, 166584t 5) Jpn. Kokai Tokkyo Koho 85, 228,460 1985; Chem. Abstr. 104, 148756n 6) Park, K.K.; Han, D.; Shin, D. Bull. Korean Chem. Soc. 1986, 7, 201 7) Burge, J.R.; Prey, P.A. J. Org. Chem. 1996, 61, 530 8) Ohta, A.; Matsunaga, M.; Iwata, N.; Watanabe, T. Heterocycles 1977, 8, 351; Chem. Abstr. 88, 74373n 9) Bryce, M.R.; Eaves, J.G.; Parker, D.; Howard, J.A.K.; Johnson, O. J. Chem. Soc., Perkin Trans 2 1985, 433; Chem. Abstr. 103, 5770f 10) Omar, N.M.; Bayomi, S.M. Egypt. J. Pharm. Sci. 1975, 16, 49; Chem. Abstr. 87, 682226e
Rohm and Haas : the Sodium Borohydride Digest
11) Elguero, J.; Jacquier, R.; Mignonac-Mondon, S. Bull. Soc. Chim. Fr. 1972, 2807; Chem. Bastr. 78, 29668v 12) Kasmetani, RT.; Okawara, T. J. Chem. Soc. Perkin Trans. 1 1977, 579; Chem. Abstr. 87, 39710c 13) Sigh, H.; Kumar, K.S. J. Chem. Sci. 1975, 1, 18; Chem. Abstr. 85, 192683z 14) Ger. Offen. 3,244,594 1984; Chem. Abstr. 101, 151766j 15) Sharma, N.D.; Goyal, V.K.; Joshi, B.C. Croat. Chem. Acta 1976, 48, 317; Chem. Abstr. 86, 106326b 16) Verma, P.N.; Sharma, N.D.; Goyal, V.K.; Joshi, B.C. Acta Cienc. Indica Chem. 1980, 6, 213; Chem. Abstr. 95, 80686c 17) Zoltewicz, J.A.; Dill, C.D.; Abboud, K.A. J. Org. Chem. 1997, 62, 6760 18) Seeman, J. Synthesis 1977, 498; Chem. Abstr. 87, 151934e 19) Zoretic, P.A.; Branchaud,B.; Sinha, N.D. J. Org. Chem. 1977, 42, 3201; Chem. Abstr. 87, 151923a 20) Leed, A.R.; Boettger, S.D.; Ganem, B. J. Org. Chem. 1980, 45, 1098; Chem. Abstr. 92, 198143q 21) Alberola, A.; Gonzalez,A.M.; Laguna, M.A.; Pulido, F. J. Synthesis 1982, 1067; Chem. Abstr. 98, 179256m
*For Online Consulting Only
press -F for Searching
112
22) Hori, M.; Kataoka, T.; Shimizu, H.; Imai, Y. Fujimura, H. Yakugaku Zasshi 1975, 95, 634; Chem. Abstr. 83, 193149a 23) Calrke, G.M.; Sykes, P. J. Chem. Soc. (C) 1967, 1269; Chem. Abstr. 67, 72972z 24) Oehl, R.; Lenzer, G.; Rosenmund, P. Chem. Ber. 1976, 109, 705; Chem. Abstr. 84, 121687x 25) Hung. Teljes 27,692 1983; Chem. Abstr. 100, 192140y 26) Walker, G.N. J. Org. Chem. 1961, 26,2740; Chem. Abstr. 55, 27301I 27) Degani, I; Fichi, R J. Chem. Soc., Perkin Trans 1 1976, 323; Chem. Abstr. 84, 121361m 28) Safieddine, A.; Royer,J.; Dreux, J. Bull. Soc. Chim. Fr. 1972, 2510; Chem. Abstr. 77, 151294q 29) Muljiani, Z; Talik, B.D. Indian J. Chem. 1969, 7, 28; Chem. Abstr. 70, 87449v 30) Iddon, B.; Suschitzky, H.; Taylor, D.S.; Chippendale, K.E. J. Chem. Soc., Perkin Trans 1 1974, 2500; Chem. Abstr. 82, 111966g 31) Borch, R.F. J. Org. Chem. 1969, 34, 627; Chem. Abstr. 70, 106088v 32) Poliaszek, R.P.; Kaufman, C.R. J. Am. Chem. Soc. 1989, 111, 4849 33) Sassaman, Tetrahedron, 1996, 52, 10835 34) Pewarson, W.; Fang, W.K. J. Org. Chem. 1995, 60, 4960; Chem. Abstr. 123 313721
Rohm and Haas : the Sodium Borohydride Digest
35) Gupton, J.T., Layman, W.J. J. Org. Chem. 1987, 52, 3683 36) Roberts, D.; Jopule, J.A.; Bos, M.A.; Alvarez, M. J. Org. Chem. 1997, 62, 568
*For Online Consulting Only
press -F for Searching
113
(including several cyclopropenyl derivatives) (7-14) as well as the synthesis of specific isotopically labeled compounds:
E. Miscellaneous Organic Reductions CARBONIUM IONS
H
Alembic: 6
C+
A variety of carbonium ions (R3C+) including aryl carbonium (1-6). Cyclopropenium (7-10), vinyl carbonium (>C=C-R2) (11-13) and heteroatoms stabilized carbonium ions (14-18) have been reduced with sodium borohydride to the parent hydrocarbons (R3CH): (C6H5)3C+Cl- + NaBH4 Æ(C6H5)3CH H C+ R'
H NaBH4
C H
H+ C
C
H
R'
R
R' "R
ClO4-
NaBH4 R
R' "R
R
H C H
H C
R
This reduction has been useful for preparation of specific pharmacologically interesting molecules
*For Online Consulting Only
114
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest
R'
ClO4R
H NaBT4
C R'
T R
Via reduction of carbonium ion intermediates, several workers have been able to trap these intermediates thus substantiating specific reaction paths (11). In systems where other nucleophiles are absent, intensely colored carbonium ions such as malachite green (2) and crystal violet (19) are rapidly reduced allowing their use for determination of low concentrations of sodium borohydride. References: 1) Olkah, G.A. Svobada, J.J. J. Am. Chem. Soc. 1973, 95, 3794; Chem. Abstr. 97, 31150j 2) Bunton, C.A.; Huang, S.K.; Paik, C.H. J. Am. Chem. Soc. 1975, 97, 6262; Chem. Abstr. 83, 192173s 3) Bunton, C.A.; Huang, S.K.; Paik, C.H Tetrahedron Lett. 1976, 1445; Chem. Abstr. 85, 108063s 4) Gribble, G.W.; Leese, R.M.; Evan, B.E. Synthesis 1977, 172; Chem. Abstr. 86, 170986u
Rohm and Haas : the Sodium Borohydride Digest
5) Fry, A.J. et. al. Tetrahedron Lett. 1976, 4803; Chem. Abstr. 87, 5056d 6) Buton, C.A.; Carrasco, N. Watts, W.E. J. Chem. Soc., Chem. Commun. 1977, 529; Chem. Abstr. 87, 200400p 7) U.S. 3,654,324 1972; Chem. Abstr. 76, 153229a 8) Pawlowski, N.E.; Lee D.J.; Sinnhuber, R.O. J. Org. Chem. 1972, 37, 3245; Chem. Abstr. 77, 164069 9) U.S. 3,699,146 1972; Chem. Abstr. 78, 57859b 10) Mata-Segreda, K.J.F.; Schowen, R.L. J. Org. Chem. 1981, 46, 644; Chem. Abstr. 94, 833332z 11) Wigfield, D.C.; Feiner, S.; Taymaz, K. Tetrahedron Lett. 1972, 895; Chem. Abstr. 76, 126140h 12) Hrazdina, G. Phytochemistry 1972, 11, 3491; Chem. Abstr. 78, 43208b 13) Creary, X. J. Org. Chem. 1976, 41, 3734; Chem. Abstr. 85, 176498n 14) Greenberg, S.; Moffatt, J.G. J. Am. Chem. Soc. 1973, 95, 4016; Chem. Abstr. 79, 42796a 15) Wudl, F. et. al. J. Org. Chem. 1974, 39, 3608; Chem. Abstr. 82, 16720po 16) Stahl, I. Chem. Ber. 1985, 118, 3166; Chem. Abstr. 103, 215243n 17) Hirai, K.; Sugimoto, H.; Ishiba, T. J. Org. Chem. 1977, 42, 1543; Chem. Abstr. 86, 188865p
*For Online Consulting Only
press -F for Searching
115
18) Tobia, D.; Rickborn, B. J. Org. Chem. 1986, 51, 3849; Chem. Abstr. 105, 208214s 19) Rudie, C.N.; Demko, P.R. J. Am. Oil Chem. Soc. 1979, 56, 520; Chem. Abstr. 90, 214801u
O
REDUCTIVE CLEAVAGES
X
R" Y
NaBH4 EtOH
R'
R"
X
H
H N
R
N
OH
R
N H2N
OH
N N
N
N
H2N
HO
CH3 N
H (2)
N N
H
N H
N
HO
H
NaBH4 (3)
Reductive cleavages of imides (4-6) and decyanation (7,8) have been reported: O O R
O NH O
*For Online Consulting Only
O
NaBH4
X or Y = NR2, OR, SR
Reductive cleavage of one of the two alkylidene carbonheteroatom bonds is generally effected in this reduction. In many of the examples reported, the functional groups containing the heteroatoms are part of the same molecule (1), allowing for ring opening under mild conditions, so as not to effect other functional groups in the compound.
H N
Sodium borohydride reductive cleavages or hydride displacements, are known in several classes of compounds. The most commonly employed reaction involves the reductive cleavage of N, N’- N,O-, O,O’-, N,S- linked alkylidene compounds: R'
116
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest
NH2
NaBH4
(5) R
O
O
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest
N
Ph
NaBH4
N
Ph CN
(7)
H
Reductive cleavage with NaBH4 is a commonly used method in the study of glycoproteins and related compounds (9,12). IT has frequently been applied to ring opening reactions of barituric acids (13,14), furans (15,16), pyrans (17), oxazines (18), benzothiazoles (19) and cyclic α-nitroketones (20). It also finds uses in cleaving side chains of azeidine compounds (21,22). Cyanoborohydride has been used to reductively cleave N-O bonds (23) , while lithium borohydride (24) and sodium borohydride (25) have been used to cleave C-N bonds in high yields. Silicon oxygen bonds have been reductively cleaved with tetrabutyl ammonium borohydride (26) and C-O have been reduced to a methyl and hydoxy group with sodium borohydride. (27) Sulfur Nitrogen bounds have been reductively cleaved to form amine and thioketone groups. (28)
*For Online Consulting Only
117
References: 1) Shimizu, K.; Ito, K.; Sekiya, M. Chem. Pharm. Bull. 1974, 22, 1256; Chem. Abstr. 81, 120403c 2) U.S. 3,983,118 1976 3) U.S. 3,714,186 1973; Chem. Asbstr. 82, 170620m 4) Rautio, M. Farm. Aikak. 1974, 83, 131; Chem. Abstr. 82, 170620m 5) Parker, W.L.; Johnson, F. J. Org. Chem. 1973, 38, 2489; Chem. Abstr. 79, 53201d 6) Jpn. Kokai Tokkyo Koho 84, 161,3445 1984; Chem. Abstr. 102, 149102s 7) Jpn. 74 19,243 1974; Chem. Abstr. 82, 97816z 8) Takahashi, K.; Kurita, H.; Ogura, K.; Ida, H. J. Org. Chem. 1985, 50, 4368; Chem.Abstr. 103, 178145j 9) Liao, M.J.; Huang, K.S.; Khorana, H.G. J. Biol. Chem. 1984, 259, 4200; Chem. Abstr. 100, 187575h 10) Sahimamura, M.; Inoue, Y., S. Arch. Biochem.. Biophys. 1984, 232, 699; Chem. Abstr. 101, 106875h 11) Ud-Din, N.; Jeanloz, R.W. et. al. J. Biol. Chem. 1986, 261, 1992; Chem. Abstr. 104, 166504h 12) Mawhinney, T.P. J. Chromatog. 1986, 351, 91; Chem. Abstr. 104, 65133f 13) Rautio, M. Acta Chem. Scand. Ser. B. 1979, B33, 770; Chem. Abstr. 93, 71685h 14) Rautio, M.; Heeso, A.; Rahkamaa, E. Arch. Pharm. (weinheim) 1981, 314, 622; Chem. Abstr. 95, 114299w
Rohm and Haas : the Sodium Borohydride Digest
15) Jpn. Kokai Tokkyo Koho 79,109,972 1979; Chem. Abstr. 92, 164251h 16) Eur. Pat. Appl. 153, 890 1985; Chem. Abstr. 104, 224716s 17) U.S. 4,199,515 1980; Chem. Abstr. 93, 95129f 18) Marco, J.L. Royer, J.; Husson, H.P. Tetrahedron Lett. 1985, 26, 6345; Chem. Abstr. 105, 78464k 19) Liso, G.; Trapani, G.; Reho, A.; Latofa, A. Synthesis 1985, 288; Chem. Abstr. 104, 88471d 20) U.S. 4,554,387 1985; Chem.Abstr. 104, 185986h 21) Eur. Pat. Appl. 62,876 1982; Chem. Abstr. 98, 107072e 22) Ger. Offen. 3,229,439 1983; Chem. Abstr. 99, 5435z 23) Wade, P.A.; Tao, J.A.; Bereznak, J.F.; Yuan, C.K. Tetrahedron Lett. 1989, 30, 5969 24) Gupta, R.B.; Franck, R.W. J. Am. Chem. Soc. 1989, 111, 7668 25) Barluenga, J.; Kouznetsov, V.; Rubio, E.; Tomas, M. Tetrahedron Lett. 1993, 34, 1981 26) Micouin, L.; Quirion, J.C.; Husson, H.P. Tetrahedron Lett. 1996, 37, 849 27) Firouzabadi, H.; Afsharifar, G.R Synth. Commun. 1996, 26, 1065 28) Kim, H.K..; Lee, Y.Y.; Kim, K.; Kim, J.H. Bull. Korean Chem. Soc. 1994, 15, 273
*For Online Consulting Only
press -F for Searching
118
119
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest
have been prepared by NaBH4 reductive cyclization of imines (13-16).
REDUCTIVE CYCLIZATION Several interesting reductive cyclization involving sodium borohydride have been reported. For instance, NaBH4 reduction of beta and gamma keto (aldehydro) esters (or acids) yields lactone derivatives in good yields (1-8):
R"
R" NR' N
O
CCl3 O
R
NaBH4 R
O
O
O
Reduction of aromatic beta and gamma keto acids leads directly to lactone formation (9-12).
N N
In contrast to the above, where only sodium borohydride was employed to effect the reductive cyclization, Coutts has used NaBH4 catalyzed by palladized charcoal to prepare heterocyclic hydroamic acids, such as quinolones and hydroxyquinolones (17,18) from o-nitro esters,
O
O
O
H
H OH
R'
NaBH4
CN
R'
R' OH NaBH4 R "R O
O R
Similarly, quinazoline derivatives, many showing anti-inflammatory and analgesic activities,
*For Online Consulting Only
CN
"R
NO2
NaBH4
CO2Et Pd/C
N H
N OH
O CN
O
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest
and bezothiazine hydroamic acids and their lactams from a-(o-nitrophenylthio) esters, acids and cinnamates (19-21) S
R'
"R CO R 2 NO2
R'
NaBH4
S
Pd/C
N
R"
O
OH
Recent publications include reductive cyclization of gamma imino compounds (22,23) photocatalyzed NaBH4 cyclizations (24-27) and even cyclization to form epoxides (28,29) Organic compounds containing alkenes and halides, tin trichlorides or hydrazones are reductively cyclized with sodium borohydride or cyanoborohydride to from cyclic hydrocarbons. (30,31,32 ) Cyclic amines can be formed by the reductive amination/cyclization of ketones with amines or azides with borohydrides.(33,34) The five membered rings contained in Protocin C and D can be synthesized the same methodology. (35). It has been demonstrated that imines and O-mesty groups can be reductively cycilized to form cyclic amines in high yields with NaBH in MeOH (36). Other functional groups that have been
*For Online Consulting Only
120
used to form cyclic amines are amides and aldehydes. (37,38). References: 1) Brownbridge, P.; Warren, S. J. Chem. Soc., Chem. Commun. 1977, 465; Chem. Abstr. 88, 37213q 2) U.S. 4,031,113 1977; Chem. Abstr. 87, 135031c 3) Spry, D.O. J. Org. Chem. 1975, 40, 2411; Chem. Abstr. 83, 97171f 4) Jpn. Kokai Tokkyo Koho 83 13,572 1983; Chem. Abstr. 99, 38365e 5) Bates, H.A.; Deng, P-N. J. Org. Chem. 1983, 48, 4479; Chem. Abstr. 99, 212331c 6) Jpn. Kokai Tokkyo Koho 83, 154,572 1983; Chem. Abstr. 100, 66612r 7) Rao, A.V.R.; Sreenivasan, N.; Reddy, D.R.; Deshpande, V.H. Tetrahedron Lett. 1987, 27, 455 8) Lange, G.L.; Organ, M.G. J. Org. Chem. 1996, 61, 5358 9) Meyer , W.L.; Vaughn, W.R. J. Org. Chem. 1957, 22, 98; Chem. Abstr. 51, 11316g 10) Cava, M.P.; Van Meter, J. P. J. Org. Chem. 1969, 34, 538; Chem. Abstr. 70, 106288k 11) Oren, J.; Schleifer, L.; Shmueli, U.; Fuchs, B. Tetrahedron Lett. 1984, 25, 981; Chem. Abstr. 101, 37932k 12) Newman, M.S.; Dhawan, B.; Khanna, V.K. J. Org. Chem. 1986, 51, 1631; Chem. Abstr. 104, 206875p
Rohm and Haas : the Sodium Borohydride Digest
13) Jpn. Kokai 72 14,183 1972; Chem. Abstr. 77, 140123g 14) Ger.Offen 2,166327 1973; Chem. Abstr. 84, 180271e 15) Walser, A. et. al. J. Org. Chem. 1978, 43, 936; Chem. Abstr. 88, 12122s 16) U.S. 3,895,032 1975; Chem. Abstr. 83, 193094d 17) Coutts, R.T.; Wibberley, D.G.; J. Chem. Soc. 1963, 4610; Chem. Abstr. 59, 12799e 18) Coutts, R.T. J. Chem. Soc. C 1969, 713; Chem. Abstr. 70, 96351j 19) Coutts, R.T. et. al. Can. J. Chem. 1965, 43, 3221; Chem. Abstr. 64, 5083b 20) Coutts, R.T. et. al. Can. J. Chem. 1966, 44, 1733; Chem. Abstr. 65, 8810d 21) Coutts, R.T. et. al. Can. J. Chem. 1967, 45, 975; Chem. Abstr. 67, 11467s 22) U.S. 4,229,455 1980; Chem. Abstr. 94, 156906b 23) Jpn. Kokai Tokkyo Koho 83 41,864 1983; Chem. Abstr. 101, 91321y 24) Ninomyia, I.; Hashimoto, C.; Kiguchi, T.; Naito, T. J. Chem. Soc., Perkin Trans. 1 1985, 941; Chem. Abstr. 103, 160747x 25) Jpn. Kokai Tokkyo Koho 84, 53, 485 1984; Chem. Abstr. 101, 91321y
*For Online Consulting Only
press -F for Searching
121
26) Jpn. Kokai Tokkyo Koho 85 56,978 1985; Chem. Abstr. 103, 160753w 27) Naito, T.; Kojima, N.; Miyata, O.; Ninomiya, I. J. Chem. Soc., Chem. Commun. 1985, 1611; Chem. Abstr. 104, 225079y 28) Zhao, D.; Zhong, J. et. al. Yaoxue Xuebao 1982, 17, 28; Chem. Abstr. 96, 199248x 29) Ger. Offen. 3,426,906 1986; Chem. Abstr. 105, 97473d 30) Stork, G.; Sher, P.M. J. Am. Chem. Soc. 1986, 108, 303 31) Hanessian, S.; Leger, R. J. Am. Chem. Soc. 1992, 114, 3115 32) Taber, D.F.; Wang, Y.; Stachel, S.J. Tetrahedron Lett. 1993, 34, 6209 33) Manescalchi, F.; Nardi, A.R.; Savoia, D. Tetrahedron Lett. 1994, 35, 2775 34) McClure, C.K.; Mishra, P.K.; Grote, C.W. J. Org. Chem. 1997, 62, 2437 35) Heathcock, C.H.; Brown, R.C.D.; Norman, T.C. J. Org. Chem. 1998, 63, 5013 36) Aelterman, W.; De Kiompe, N.; Declercg, J. Org. Chem. 1998, 63, 6 37) Wang, X.; De Silva, S.O.; Reed, J.N.; Billadeau, R.; Griffen, E.J.; Chan, A.; Snieckus, V. Org. Synth. 1993, 72, 163 38) Dinsmore, C.J.; Ingman, J.M. J. Org. Chem. 1998, 63, 4131
Rohm and Haas : the Sodium Borohydride Digest
DEHALOGENANTIONS Alembic: 9, 52, 55, 61 Under normal reaction conditions, alkyl and aryl halides are inert to NaBH4. Under solvolytic conditions, however, secondary and tertiary alkyl halides which are capable of forming stable carbonium ions are reducible to the corresponding hydrocarbon (13). Good to excellent yields are reported in dehalogenantion of bezhydril chloride to diphenyl methane, t-cumyl chloride to cumene and triphenyl methyl chloride to triphenylmethane. (See also section on carbonium ion reductions.) In addition, several authors have reported dehalogenantion of gem-dihalo compounds with sodium borohydride (4,5). New developments in the catalyzed NaBH4 reduction of halo compounds have broaden the applicability of this reaction.(6-8) Photo-catalyzed reduction of halogenated aromatic hydrocarbons has been reported (9-11). Inorganic catalysts such as palladium chloride or nickel chloride (in situ nickel boride) have proven effective for site specific deuteration of aryl halides (12,13), for dechlorination of various pesticides and PCB’s (14-17) and for analytical determination of organic solids bound halides (18,19).
*For Online Consulting Only
press -F for Searching
122
Dicyclopentadienyltitanium dichloride has also been used to catalyze NaBH4 dehalogenantions (20). The combination of triakly tin halides with NaBH4, in which the dehaolganting agent is R3SnH has been used to advantage (21-23). Other main group alkyl reagents can catalytically dehalogenate aromatic and aliphatic halides with sodium borohydride. (24) Tetrabutylamonnium borohydride can reduce aromatic and aliphatic halogenated compounds in THF in high yields. (25). PCB’s can be reduced in diglyme at elevated temperatures with NaBH4 or NaBH4 and LiCl (26). LiBH4 can dehalogenate both aromatic and aliphatic halides chemoselectively. (27) Alkyl halides are reduced with borohydride exchange resins spiked with Ni(OAc)2 at room temperature.(28) Zinc cyanoborohydride can dehalogenate both aromatic and aliphatic halides at the reflux temperature of methanol. (29) γ-Lindene and α-chlorotolulene can be completely dehalogenated with NaBH2(OCH2CH2OCH3)2 at elevated temperatures. (30) The addition of transition metal chlorides to the above stated reagent such as PdCl2 and NiCl2 have dehalogenated chlorophenols and chlorobenzenes. (31) Other alkoxy borohydrides have declorinated PCB’s at the reflux temperature of THF (32) Recent applications include the preparation of tritium labeled retinoic acid (33) CNS-active 2,3-dihydroergolines (34) and triabicycloheptane substituted prostaglandin
Rohm and Haas : the Sodium Borohydride Digest
analogues (35), which are cardiovascular agents useful in treating thrombotic disease. Allylic chlorides have been dechlorinated with sodium borohydride to form bucky ball type structures. (36) References: 1) Brown, H.C.; Bell, H.M.; J. Org. Chem. 1962, 27, 1928; Chem. Abstr. 57, 12353g 2) Bell, H.M.; Brown, H.C. J. Am. Chem. Soc. 1966, 88, 1473; Chem. Abstr. 64, 15695c 3) St. Clair, T.L.; Diss Abstr. Int. B 1972, 33, 200; Chem. Abstr. 78, 57424f 4) Groves, J.T.; MA. K.W. J. Am. Chem. Soc.; 1974, 96, 6527; Chem. Abstr. 81, 151239h 5) Levitin, I.Y.; Dvoletski, M.; Volpin, M.E. Kinet. Katal. 1972, 13, 690; Chem. Abstr. 77, 100449m 6) Schwartz, J.; Liu, Y.; J. Org. Chem. 1994, 59, 940 7) Schwartz, J.; Liu, Y. Tetrahedron 1995, 51, 4471 8) Cavallaro, C.L.; Liu, Y.; Schwartz, J.; Smith, P. New J. Chem. 1996, 20, 253 9) Barltrop, J.A.; Bradbury, D. J. Am. Chem. Soc. 1973, 95, 5086; Chem. Abstr. 79, 85589c 10) Tsuijmoto, K.; Tasaka, S.; Ohashi, M. J. Chem. Soc., Chem. Commun. 1975, 758; Chem. Abstr. 83, 192246t
*For Online Consulting Only
press -F for Searching
123
11) Abeywickrema, A.N.; Beckewith, A.L. J. Tetrahedron Lett. 1986, 27, 109; Chem. Abstr. 105, 171926x 12) Bosin, T.R.; Raymond, M.G.; Buckpitt, A.R.; Tetrahedron Lett. 1973, 4699; Chem. Abstr. 80, 120462a 13) Stiles, M. J. Org. Chem. 1994, 59, 5381 14) Dennis, W.H.; Cooper, W. J. Bull. Environ. Contam. Toxicol. 1975, 14, 738; Chem. Abstr. 84, 100851f 15) Dennis, W.H.; Cooper, W. J. Bull. Environ. Contam. Tpoxicaol. 1976, 16, 425; Chem. Abstr. 86, 66792s 16) U.S. Pat. Appl. 794,928 1986; Chem. Abstr. 104,229975k 17) Kozloski, R.J. J. Chromatr. 1985, 318, 211; Chem. Abstr. 102, 124849c 18) Lassova, L.; Lee, H.K.; Hor, T.S.A. J. Org. Chem. 1998, 63, 3538 18) Egil, R.A. Helv. Chim. Acta 1968, 51, 2090; Chem. Abstr. 70, 28501h 19) Egli, R.A. Z. Anal. Chem. 1969, 247, 39; Chem. Abstr. 71, 131377s 20) Meunier, B. J. Organomet. Chem. 1980, 204, 345; Chem. Abstr. 94, 191816u 21) Parnes, H.; Pease, J. J. Porg. Chem. 1979, 44, 151; Chem. Abstr. 90, 55156u 22) Corey, E.J.; Marfat, A.; Hoover, D. J. Tetrahedron Lett. 1981, 22, 1587; Chem. Abstr. 95, 114733h
Rohm and Haas : the Sodium Borohydride Digest
23) Gurjar, M.K.; Yadav, J.S.; Rama Rao, A.V. Indian J. Chem. Sect. B 1983, 22b, 1139; Chem. Abstr. 101, 91377w 24) Nakamura, T.; Yorimitsu, H.; Shinokubo, H.; Oshima, K. Synlett 1999, 1415 25) Narasimhan, S.; Swamalakshmi, S.; Balakumar, R.; Velmathi, S. Synth. Commun. 1999, 29, 685 26) Yang, C.; Pittman, C.U. Tetrahedron Lett. 1997, 38, 6561 27) Cho, B.T.; Yoon, N.M. J. Korean Chem. Soc. 1983, 27, 46 28) Yoon, N.M.; Lee, H.J.; Ahn, J.H.; Choi, J. J. Org. Chem. 1994, 59, 4687 29) Kim, S.; Kim, Y.J.; Ahn, K.H. Tetrahedron Lett. 1983, 24, 3369 30) Tabaei, S.M.H.; Pittman, C.U. Haz. Waste Haz. Mater. 1993, 10, 431 31) Tabaei, S.M.H.; Pittman, C.U. Tetrahedron Lett. 1993, 34, 3263 32) Tabaei, S.M.H.; Pittman, C.U.; Mead, K.T. J. Org. Chem. 1992, 57, 6669 33) Ger Offen. 3,142,975 1983; Chem. Abstr. 99, 71034u 34) Ger Offen. 3,411,981 1985; Chem. Abstr. 105, 43137d 33) U.S. 4,588,742 1986; Chem. Abstr. 105, 78746d
*For Online Consulting Only
press -F for Searching
34) Zhang, H.R.; Wang, K.K. J. Org. Chem. 1999, 64, 7996
124
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest
33), prostaglandin derivatives (19, 20,34,35), porphyrins (36,37) and avermectins (38).
DEMERCURATIONS The oxymercuration of olefinic bonds, followed by reductive demercuartion with sodium borohydride, is an extremely efficient method for the stereoselective, high yield Markownikov hydration of olefins: (1) OH
Hg(OAc)2 R
CH2
R THF/H2O
OH
HgOAc NaBH4 NaOH
H H
R H
This procedure originally developed by H.C. Brown et. al. (2) has been the subject of two review articles (3,4). The mechanism (5-8) and stereochemical implication (9-12) of this reaction have been investigated extensively. From extensions of this basic reaction, new synthetic methods have been developed to provide alkylation (13-16) and cyclization (17-20) reactions, peroxymercuration (21,22), aminomercuration (23-25) and azidomercuration (26). Phase transfer catalysis (27-28) and micelle mediation (29-30) have been applied to oxymercuration demercuration reactions. Demercuration with NaBH4 has found practical applications in the synthesis of juvenile hormones (31*For Online Consulting Only
125
References: 1) Russell, G.A.; Jiang, W.; Hu, S.S.; Khanna. R.K. J. Org. Chem. 1986, 51, 5499 2) Brown, H.C.; Geoghegan, P. J. Am. Chem. Soc. 1967, 89, 1522; Chem. Abstr. 67, 99540u 3) Lorock, C. Angew. Chem. Int. Ed. Engl. 1978, 17, 27 4) Seyferth, D. Organomet. Chem. Rev., Sec. B, Ann. Rev. 1971, 8, 425; Chem. Abstr. 76, 59682w 5) Quirk, R.P.; Lea, R.E. J. Am. Chem. Soc. 1976, 98, 5973; Chem. Abstr. 85, 191940u 6) Pasto, D.J.; Gontarz, J. A. J. Am. Chem. Soc. 1971, 93, 6902; Chem. Abstr. 76, 33692z 7) Pasto, D.J.; Gontarz, J. A. J. Am. Chem. Soc. 1969, 91, 719; Chem. Abstr. 70, 67337d 8) Giese, B.; Kretzschmar, G. Chem. Ber. 1984, 117, 3175; Chem. Abstr. 102, 61581m 9) Jasseerand, D. et. al. Tetrahedron 1976, 32, 1535; Chem. Abstr. 86, 43091y 10) Kitching, W.; Atkins, A.R.; Wickham, G.; Albert, V. J. Org. Chem. 1981, 46, 563; Chem. Abstr. 94, 83505h 11) Harding, K.E.; Marman, T.H. J. Org. Chem. 1984, 49, 2838; Chem. Abstr. 101, 72865n
Rohm and Haas : the Sodium Borohydride Digest
12) Gouzoules, F.H.; Whitney, R.A. J. Org. Chem. 1986, 51, 2024 13) Giese, B.; Meister, J. Chem. Ber. 1977, 110, 2588; Chem. Abstr. 87, 133845x 14) Henning, R.; Uraback, H. Tetrahedron Lett. 1983, 24, 5343; Chem. Abstr. 100, 139572q 15) Barluenga, J.; Campos, P.J.; Lopez-Padro, J.; Asensio, G. Synthesis 1985, 1985, 1125; Chem. Abstr. 105, 171935z 16) Bellec, N.; Guillemin, J.C. Tetrahedron Lett. 1995, 36, 6883 17) Harding, K.E.; Burks, S.R. J. Org. Chem. 1981, 46, 3920; Chem. Abstr. 95,115183r 18) Carruthers, W.; Williams, M.J.; Cox, M.T. J. Chem. Soc., Chem. Commun. 1984, 1235; Chem. Abstr. 102, 131883n 19) Jpn. Kokai Tokkyo Koho 84 10,577 1984; Chem. Abstr. 101, 90657a 20) Jpn. Kokai9 Tokkyo Koho 85, 243,079 1985; Chem. Abstr. 104, 207038e 21) Bloodworth, A.J.; Courtneidge, J.L. J. Chem. Soc., Perkin Trans. 1 1982, 1807; Chem. Abstr. 97, 198305x 22) Corey, E.J.; Schmidt, G.; Shimoji, K. Tetrahedron Lett. 1983, 24, 3169; Chem. Abstr. 100, 34340j
*For Online Consulting Only
press -F for Searching
126
23) Barluenga, J.; Perez-Prieto, J. Bayon, A.M.; Asensio, G. Tetrahedron 1984, 40, 1199; Chem. Abstr. 101, 171056f 24) Davtyan, S.Z.; Badanyan, S.O. Arm. Khim. Zh. 1983, 36, 508; Chem. Abstr. 100, 67447c 25) Roubaud,V.; Le Moigne, F.E.; Mercier, A.; Mordo, P. Synth. Commun. 1996, 26, 1507 26) Grunewald, G.L.; Bartlett, W.J. et. al. J. Med. Chem. 1986, 29, 1972; Chem. Abstr. 105, 225990j 27) Rolla, F. J. Org. Chem. 1981, 46, 3909; Chem. Abstr. 95, 114927z 28) Barluenga, J.; Lopez-Prado, J.; Campos, P.J.; Asensio G. Tetrahedron 1983, 39, 2863; Chem. Abstr. 100, 68122e 29) Link, C.M.; Jansen, D.K.; Sukenik, C.N. J. Am. Chem. Soc. 1980, 102, 7798; Chem. Abstr. 94, 30237r 30) Sutter, J.K.; Sukenik, C.N. J. Org. Chem. 1984, 49, 1295; Chem. Abstr. 100, 138928y 31) U.S. 3,923,868 1975; Chem. Abstr. 84, 58672w 32) Camps, F.; Coll, J.; Seba, M.E. An. Quim. 1979, 75, 401; Chem. Abstr. 91, 210947u 33) Tolstikov, G.A.; Rozenstsvet, O.A. Izv, Akad. Nauk SSSR, Ser. Khim. 1984, 816; Chem. Abstr. 101, 170676w 34) Corey, E.J.; Kewck, G.E.; Szekely, I J. Am. Chem. Soc. 1977, 99, 2006; Chem. Abstr. 86, 189264d 35) Suzuki, M.; Yanagisawa,A.; Noyori, R. Tetrahedron Lett. 1983, 24, 1187; Chem. Abstr. 99, 70430h
Rohm and Haas : the Sodium Borohydride Digest
36) Smith, K.M.; Langry, K.C. J. Org. Chem. 1983, 48, 500; Chem. Abstr. 98, 89036k 37) Smith, K.M.; Langry, K.C.; Minnetian, O.M. J. Org. Chem. 1984, 49, 4602; Chem. Abstr. 101, 230212d 38) U.S. 4,423,209 1983; Chem. Abstr. 100, 175208j
*For Online Consulting Only
press -F for Searching
127
128
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest
DOUBLE BONDS Olefinic bonds are reducible by sodium borohydride only when activated. Any functional group which sufficiently polarizes the double bond can activate this group for borohydride reduction. Several classes of activated double bonds have been reported including: α−β unsaturated nitriles (1-4), aldehydes, ketones (5), nitro (6,8), esters (9-11) and lactones (12,13): carbon-carbon double bonds alpha to an aryl ring (14,15); unsaturated amines (e.g. enamines 16-21). Several examples where activated double bonds have been reduced are shown below:
R"
R"
N
N NaBH4
N
N
(17)
R
R N
N
R'
R' O
O
O
O O
O O
NaBH4
O
O O
(20)
NMe NaBH4
HN
NMe (16)
AcO
AcO
O2N
H H O2N C
H C
NaBH4
HN
O
O CO2R
*For Online Consulting Only
(22)
CO2R
O
R
O NaBH4
NaBH4
R
O
O
OH
OH
hυ (23)
H
129
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest
OH
R
H
HO
OH
This type of reaction is used to convert a dihydropyridine to the tetrahydro from in the manufacture of the substituted benzazocines (24) which are used as analgesic agents. Several authors have recently reported the use of sodium borohydride for reduction of photo excited aromatic compounds (25,26):
*For Online Consulting Only
OH
Catalyzed NaBH4 reduction of acetylenes to olefins has also been reported (27-29). Metal salt such as BiCl3, Cu2+, NiCl2 and CoCl2 have been used to modify the reactivity of sodium borohydride so that it can easily reduce olefins to alkanes. (30-35). The use of low molecular weight alcohols and acetic acids with sodium borohydride to promote the reduction of alkenes to alkanes has been demonstrated. (36-38) Zinc borohydride has been shown to reduce primary nitroalkenes to nitroalkanes while converting disubstituted nitroalkenes to oximes. (39,40) Borohydride exchange resins in MeOH at RT have reduced α−β unsaturated nitroalkenes to nitroalkanes in high yields. (41). CuSO4 and borohydride exchange resins in MeOH at RT reduces α−β unsaturated esters, amides, and cyanides to their corresponding alkane.(42) Nickel chloride
Rohm and Haas : the Sodium Borohydride Digest
and borohydride exchange resins can reduce electron deficient alkenes to alkanes in high yields.(43) Zinc borohydride supported on aluminophosphates have hydrogenated both aromatic alkenes and alkynes. (44) Selective reduction of terminal over substituted alkenes has been accomplished using calcium borohydride and MeOH in THF at reflux temperatures. (45) The use of borane generated in situ using sodium borohydride and I2 at 0o C has been shown to reduce α−β keto alkenes to alkanes. (46) References: 1) Pepin, Y.; Nazemi, H.; Payette, D. Can. J. Chem. 1978, 56, 41; Chem. Abstr. 89, 41994h 2) Toda, F.; Kanno, M. Bull. Chem. Soc. Jpn. 1976, 49, 2643; Chem. Abstr. 86, 55130y 3) Jung, M.E.; Lam, P.; Mansuri, M.M.; Speltz, L.M. J. Org. Chem. 1985, 50, 1087; Chem. Abstr. 102, 148972p 4) Vartanyan, R.S.; Shaginyan, R.S. et. al. Arm. Khim. Zh. 1985, 38, 304; Chem. Abstr. 105, 78803v 5) Formasier, R.; Lucchini, V.; Scrimin, P.; Tonellato, U. J. Org. Chem. 1986, 51, 1769; Chem.Abstr. 104, 206747y
*For Online Consulting Only
press -F for Searching
130
6) Backman, G.B.; Maleski, R.J. J. Org. Chem. 1972, 37, 2810; Chem. Abstr. 104, 206747y 7) Varma, R.S.; Kabalka, G.W. Synth. Commun. 1985, 15, 151; Chem. Abstr. 103, 53338t 8) Bhattacharjya, A.; Mukhopasdhyay, R.; Pakrashi,S.C. Synthesis 1985, 886; Chem. Abstr. 015, 42400x 9) Setoi, H.; Takeno, H.; Hashimoto, M. J. Org. Chem. 1985, 50, 3948; Chem. Abstr. 103, 1607842s 10) Wiunterfeldt, E.; Freund, R. Liebigs Ann. Chem. 1986, 1262; Chem. Abstr. 105, 60796k 11) Eur. Pat. Appl. 156,261 1985; Chem. Abstr. 104, 148757p 12) Chhowdhury, P.K.; Barua, N.C. et. al. J. Org. Chem. 1983, 48, 732; Chem. Abstr. 98, 143670c 13) El-Feraly, F.; Benigni, D.A.; McPhail, A.T. J. Chem. Soc., Perkin Trans 1 1983, 355; Chem. Abstr. 98, 215814c 14) Dauzonne, D.; Royer, R. Synthesis 1984, 1054; Chem. Abstr. 103, 5956w 15) Kametani, T.; Yukawa, H.; Suzuki, Y.; Honda, T. J. Chem. Soc., Perkin Trams. 1 1985, 2151; Chem. Abstr. 104,186682t 16) Kudo, T.; Nose, A.; Yakugaku Zasshiu 1974, 94, 1475; Chem. Abstr. 82, 125255m 17) Swiss 593,965 1977; Chem. Abstr. 88, 105181e 18) Bata, I.; Heja, G.; Kiss, P.; Korbonits, D. J. Chem. Soc., Perkin Trans 1 1986, 9; Chem. Abstr. 105, 225559a 19) Eur. Pat. Appl. 80,847 1983; Chem. Abstr. 99, 1094979p
Rohm and Haas : the Sodium Borohydride Digest
20) U.S. 3,641,005 1972; Chem. Abstr. 76, 141213c 21) Toyooka, N.; Yoshida, Y.; Yotsui, Y.; Momose, T. J. Org. Chem. 1999, 64, 4914 22) Chandrasekaran, S.; Kluge, A.F.; Edwards, J.A. J. Org. Chem. 1977, 42, 3972; Chem. Abstr. 88, 6819n 23) Chan, W.R.; Gibbs, J.A.; Taylor, D.R. J. Chem. Soc., Perkin Trans. 1 1973, 1047; Chem. Abstr. 79, 18886j 24) U.S. 3,250,678 1966; Chem. Abstr. 65, 7157g 25) Bradbury, D.; Barltrop, J. J. Chem. Soc. Chem. Commun. 1975, 842; Chem. Abstr. 84, 42863y 26) Nishiki, M.; Miyataka, H. et. al. Tetrahedron Lett. 1982, 23, 193; Chem. Abstr. 96, 217296t 27) Suzuki, N.; Tsukanaka, T. et. al. J. Chem. Soc., Chem. Commun. 1983, 515; Chem. Abstr. 99, 157759w 28) Kijuma, M.; Nambu, Y.; Endo, T. Chem. Lett. 1985, 1851; Chem. Abstr. 105, 114651e 29) Jpn. Kokai Tokkyo Koho 84 33,300 1984; Chem. Abstr. 101, 111269t 30) Narasimhan, S.; Prasad, K.G.; Madhavan, S. Tetrahedron Lett. 1995, 36, 1141 31) Cowan, J.A. Tetrahedron Lett. 1986, 27, 1205
*For Online Consulting Only
press -F for Searching
131
32) Roush, W.R.; Kageyama, M.; Riva, R.; Brown, B.B.; Warmus, J.S. Moriarty, K.J. J. Org. Chem. 1991, 56, 1192 33) Ihara, M; Tokunaga, Y.; Fukumoto, K. J. Org. Chem. 1990, 55, 4497 34) Dondoni, A.; Perrone, D.; Semola, M.T. J. Org. Chem. 1995, 60, 7929 35) Morimoto, Y.; Iwahashi, M. Synlett 1995, 1221 36) Varma, R.S.; Kabalka, G.W. Synth. Commun. 1985, 15, 151 37) Hanessian, S.; Roy P.J.; Petrini, M.; Hodges, P.J.; Di Fabio, R.; Carganico, G. J. Org. Chem. 1990, 55, 5766 38) Rao, C.S.; Chakrasali, R.T.; Ila, H.; Junjappa, H. Tetrahedron 1990, 46, 2195 39) Ranu, B.C.; Chakraborty, R. Tetrahedron 1992, 48, 5317 40) Ranu, B.C.; Chakraborty, R. Tetrahedron Lett. 1991, 32, 3579 41) Goudgaon, N.M.; Wadgaonkar, P.P.; Kabalka, G.W. Synth. Commun. 1989, 19, 805 42) Sim, T.B.; Yoon, N.M. Synlett 1995, 726 43) Sim, T.B.; Choi, J.; Joung, M.J.; Yoon, N.M. J. Org. Chem. 1997, 62, 2357 44) Campelo, J.M.; Chakraborty, R.; Marinas, J.M. Synth. Commun. 1996, 26, 1639 45) Narasimhan, S.; Prasad, K.G.; Madhavan, S. Tetrahedron Lett. 1995, 36, 1141
Rohm and Haas : the Sodium Borohydride Digest
46) Das, B.; Kashinatham, A.; Madhusudhan, P. Tetrahedron Lett. 1998, 39, 677
*For Online Consulting Only
press -F for Searching
132
Rohm and Haas : the Sodium Borohydride Digest
EPOXIDES Alembic 48, 50, 55 Sodium borohydride is generally unreactive toward any epoxide groups and ahs been effectively to remove impurities in materials such as ethylene oxides (1), propylene oxide (2), and glycidylmethacrylate (3). However, some authors have reported the use of sodium borohydride for selective opening of strained or activated epoxides (4-8). In some instances it is not clear whether the borohydride ion BH4- or an in situ generated derivative e.g. B(OR)3H- was actually responsible for the ring opening reaction. In sodium borohydride reduction of vicinal epoxy alcohols, only the trans epoxy alcohol and not the corresponding cis compound was reduced (9). This selective reactivity should be extremely useful in the synthesis of pharmaceutical compounds. The use of supported borohydride reagents has gained popularity in reducing many functional groups including epoxides. The use of zinc borohydride on zeolites, aluminophosphates and silica gel has been demonstrated to ring open epoxides. (10-12) Sodium borohydride in low molecular weight alcohols have been shown to reduce epoxy esters to
*For Online Consulting Only
press -F for Searching
133
diols (13) and cyclic epoxides in diglyme to mono alcohols. (14) Reduction of epoxides with cyanoborohydride and BF3•Et2O in refluxing THF has been used to synthesis natural product compounds (15,16). Lithium borohydride with titanium tetraisopropoxide has reduced epoxides to alcohols. (17). Solid state reactions of lithium borohydride in hexane and epoxides have formed the corresponding alcohols in high yield (18). The reaction of NaBH4 and PhSeSePh has been used to ring open epoxide esters at RT (19). Cyclodextrin has been used to directionlize the ring opening of styrene oxides with sodium borohydride. (20) References: 1) U.S. 3,213,113 1965; Chem. Abstr. 64, 3482g 2) Ger. 1,144,704 1963; Chem. Abstr. 59, 6367d 3) Jpn 70 17,661 1970; Chem. Abstr. 73, 87776m 4) Stevens, C.L. et. al. J. Org. Chem. 1972, 37, 3130; Chem. Abstr. 77, 151756p 5) Yoneta, T.; Matuno, T.; Nanahoshi, H.; Fukatsu, S. Chem. Pharm. Bull. 1981, 29, 3469; Chem. Abstr. 96, 143219w 6) Soai, K.; Ookawa, A.; Oyamada, H.; Takase, M. Heterocycles 1982, 19, 1371; Chem. Abstr. 97, 144694e
Rohm and Haas : the Sodium Borohydride Digest
7) Steliou, K.; Poupart, M.A. J. Am. Chem. Soc. 1983, 105, 7130; Chem. Abstr. 99, 212319e 8) Falck, J.R.; Manna, S. et. al. Tetrahedron. Lett. 1983, 24, 5715; Chem. Abstr. 100, 138804e 9) Weissenbergf, M.; Krinsky, P.; Glotter, E. J. Chem. Soc., Perkin Trans 1 1978, 565; Chem. Abstr. 89, 147129v 10) Sreekumar, R.; Padmakumar, R.; Rugmini, P. Tetrahedron Lett. 1998, 39, 5151 11) Campelo, J.M.; Chakraborty, R.; Marinas, J.M. Synth. Commun. 1996, 26, 415 12) Ranu, B.C.; Das, A.R. J. Chem. Soc., Chem. Commun. 1990, 1334 13) Lanier, M.; Pastor, R. Tetrahedron Lett. 1995, 36, 2491 14) Huwe, C.M.; Blechert, S. Tetrahedron Lett. 1995, 36, 1621 15) Tone, H.; Nishi, T.; Oikawa, Y.; Hikota, M.; Yonemitsu, O. Tetrahedron Lett. 1987, 28, 4569 16) Taber, D.F.; Houze, J.B. J. Org. Chem. 1994, 59, 4004 17) Dai, L.X.; Lou, B.L.; Zhang, Y.Z.; Guo, G.Z. Tetrahedron Lett. 1986, 27, 4343 18) Sugita, K.; Onaka, M.; Izumi, Y. Tetrahedron Lett. 1990, 31, 7467
*For Online Consulting Only
press -F for Searching
134
19) Miyashita, M, Hoshino, M.; Suzuki, T.; Yoshikoshi, A. Chem. Lett. 1988, 507 20) Ravichandran, R.; Divakar, S. J. Mol. Catal. A 1999, 137, 31
Rohm and Haas : the Sodium Borohydride Digest
ORGANO CALCOGEN COMPOUNDS Alembic: 58 A number of workers have reported the reduction of organic disulfides to thiols (1-5) and of diselenides to the corresponding selenol (6) or organoselenides anions (7-9). This reduction has been developed into a method of disulfides analysis (10) since sulfides and mercaptans do not interfere (11), and has been used to measure naturally occurring urinary disulfides in cystinuric patients (12). NaBH4 has been used to distinguished organic polysulfides from disulfides (13); in addition to thiol formation, hydrogen sulfides is produced from polysulfides, but not from disulfides. Di and polysulfide reductions have been applied to the study of trypsinogens (14), the modification of sporidesmin-type antibiotics which contain the epithiodioxopiperazine system (I) common to a number of fungal metabolites (15), the preparation of rubber crosslinking agents (16),
O
N S O
*For Online Consulting Only
(1)
S NR
135
press -F for Searching
And to the resolution of racemic cyclic disulfides (17). The combination of sodium borohydride and NiCl2 or CoCl2 has been demonstrated to desulfurize thiols, thioethers, sulfons and sulfonates in high yield. (18,19) Sodium borohydride has been demonstrated to have the ability to reduce sulfonyl chlorides to disulfides or completely remove the group with the addition of pyridine. (20-22) Borohydride exchange resins has been used to form symmetrical and unsymmetrical thioether from thiols or disulfides with organic halides in high yields. (23-25) While xanthates in general are not reduced (26), phenyl xanthates can be reduced to thiophenols (27). RO
S
NaBH4 R'
HS
R'
O
A number of recent publications show the general applicability of NaBH4 to the reduction of cationic sulfur heterocycles (28) such as benzoxathiolium (II) (29) to the corresponding thiole,
H S + X
NaBH4
S
X= O X=S
X
R1 R
R
R3
NO2
NO2 NaBH4
S
S
Se
Se
Ph
NaBH4 2 Ph
SeNa
such as nuciferine (V), and apomorphine dimethyl ether, (IV).
*For Online Consulting Only
R4 V R1=R2= OCH3; R3,R4=H ÆR1=OCH3;R2=OH;R3=R4=H VI R1=R2= H; R3,R4= OCH3 ÆR1;R2=H;R3=OH, R4=OCH3
Reduction of o-nitrophenylslenocyanate provides the arylselenium anion which was used in a synthetic sequence resulting in (a)-deoxyvernolepin (33).
S
Aryl selenium anions produced by NaBH4 reduction are proving to be synthetically useful reagents. Sodium benzylselenolate, (IV) has been used for regioselective o-demethylation of aporphine alkaloids (32)
Ph
NMe
R2
Benzodithiolium (III) (30) and thiopyrilium to the thiopyran (31).
S +
136
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest
NO2
NaBH4
SeCN
NO2 Se-
High purity symmetrical diselenides has been synthesized in excellent yield form both aliphatic and aromatic aldehydes (34) by NaBH4 reduction of a mixture of aldehyde, sodium hydrogen selenide and an amine catalyst such as piperidine or morpholine.
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest NaBH4
O
2 R
+
2 NaHSe
H
Amine
R
Se
Se
R
Use of 0.25 molar equivalent of borohydride results in maximum diselenide yield with little selenol contamination. The NaHSe is conveniently prepared by NaBH4 reduction of elemental selenium in absolute ethanol (35). NaBH4, and more recently NaBH3CN, are being applied with increasing frequency to the desulfonation of p-toluene- and methanesulfonates. This reaction is often used to convert alcohols to the corresponding hydrocarbon (36-41). The selective reduction of a mesylate in the presence of a tosylate has been reported in studies elucidating the chirality in tetrahydroquinoxalines (42). OTs N
OTs
H
N CH2OMs NaBH4
H CH3
N
N
H
H
Selenoether compounds synthesized by reducing Se metal or Alkyl dibromoselenide and *For Online Consulting Only
137
halocarbons with borohydride exchange resins or sodium borohydride. (43-45) It has been demonstrated that aryl nitriles can be reduced with NaBH4 in the presence of Se metal to form seleno amides in high yield (46) Both seleno ethers and diselenides can be reduced to selenols in high yielded with sodium borohydride. (47- 49) Telluerium ether compounds can be synthesized in high yield from the reduction of ArTeCl3 with sodium borohydride and a organic halide in THF at 0o C. (50) Di tellurides has been reduced to telluriol in high yielded using sodium borohydride. (51,52) References: 1) Bosman, W.P.; Van der Linen, H.G.M. J. Chem. Soc., Chem. Commun. 1977, 714; Chem. Abstr. 88, 145344s 2) Belg. 866,910 1978; Chem. Abstr. 90, 137816y 3) Ookawa, A.; Yokoyama, S.; Soai, K. Synth. Commun. 1986, 819; Chem. Abstr. 105, 208549e 4) Fr. Demande 2,566,400 1985; Chem. Abstr. 105, 152688e 5) Jpn. Kokai Tokkyo Koho 85, 2222, 485 1985; Chem. Abstr. 105, 78751b 6) Rinaldi, A.; Dernini, S. Dessy, M.R.; DeMarco, C. Anal. Biochem. 1975, 69, 289; Chem. Abstr. 84, 432242g
Rohm and Haas : the Sodium Borohydride Digest
7) Entwistle, I.D.; Johnstone, R.A.W.; Varley, J.H. J. Chem. Soc., Chem. Commun. 1976, 61; Chem. Abstr. 84, 121363p 8) Liotta, D.; Sunay, U.,; Santiesteban, H.; Markiewicz, W. J. Org. Chem. 1981, 46, 2605; Chem. Bastr. 95, 41572t 9) Kuroda, C.; Theramongkol, P.; Engebrecht, J.R.; White, J.D. J. Org. Chem. 1986, 51, 957; Chem. Abstr. 104, 186207s 10) Stahl, C.R.; Siggia, S. Anal. Chem. 1957, 29, 154; Chem. Abstr. 51, 17611a 11) Sjoeberg, B.; Herdevall, S. Acta Chem. Scand. 1958, 12, 1347; Chem. Abstr. 54, 2281I 12) Bir, K.; Crawhall, J.C.; Mauldin, D. Clin, Chem. Acta 1970, 30, 183; Chem. Abstr. 73, 32989t 13) Klayman, D.L.; Griffin, T.S.; Woods, T.S. Int. J. Sulfur Chem. 1973, 8, 53; Chem. Abstr. 81, 32989t 14) Sondack, D.L.; Light, A. J. Biol. Chem. 1971, 246, 1630; Chem. Abstr. 74, 107621t 15) Ottenheijm, H.C.; Herscheid, J.D.M.; Kerkhoff, G.P.C.; Spande, T.F. J. Org. Chem. 1976, 41, 3433; Chem. Abstr. 85, 160025v 16) PCT Int. Appl 84 04,921 1984; Chem. Abstr. 102, 185115g
*For Online Consulting Only
press -F for Searching
138
17) Ottenheijm, H.C.J.; Herscheid, J.D.M.; Nivard, R.J.F. J. Org. Chem. 1977, 42, 925; Chem. Abstr. 86, 140001b 18) Back, T.G.; Baron, D.L.; Yang, K. J. Org. Chem. 1993, 58, 2407 19) Alcaide, B.; Casarrubios, L.; Dominguesz, G.; Sierra, M.A. J. Org. Chem. 1994, 59, 7934 20) Suzuki, H.; Nakamura, T.; Yoshikawa, M. J. Chem. Research (S) 1994, 70 21) Volonterio, A.; Vergani, B.; Crucianelli, M.; Znadfa, M.; Bravo, P. J. Org. Chem. 1998, 63, 7236 22) Zhang, M.H.; Zheng, M.; Cheng, T.; Wang, S.X. Organic Prep. Proc. Int. 1996, 28, 467 23) Yoon, N.M.; Choi, J.; Ahn, J.H. J. Org. Chem. 1994, 59, 3490 24) Choi, J.; Yoon, N.M. Synth. Commun. 1995, 25, 2655 25) Nah. J. H.; Choi, J.; Yoon, N.M. Bull. Korean Chem. Soc. 1996, 17, 26) Lightner, D.A.; Djerassi, C. Tetrahedron 1965, 21, 583; Chem. Abstr. 62, 13206c 27) Overberger, C.G.; Lebovits, A. J. Am. Chem. Soc. 1956, 78, 4792; Chem. Abstr. 51, 1896a 28) Boyd, P.D.W.; Hope, J.; Martin, R.L. J. Chem. Soc., Dalton Trans. 1986, 8877; Chem. Abstr. 105, 90017z 29) Degani, I.; Fochi, R. Synthesis 1976, 757; Chem. Abstr. 86, 139900n
Rohm and Haas : the Sodium Borohydride Digest
30) Nakayama, J.; Fugiwaw, K.; Hishoni, M. Bull. Chem. Soc. Jpn. 1976, 49, 3567; Chem. Abstr. 86, 155545f 31) Iddon, B.; Suschitzky, H.; Taylor, D.S.; Chippendale, K.E. J. Chem. Soc., Perkin Trans 1 1974, 2500; Chem. Abstr. 82, 111966g 32) Ahmad, R.; Saa, J.M.; Cava, M.P. J. Org. Chem. 1977, 42, 1228; Chem. Abstr. 86, 155837c 33) Grieco, P.A.; Noguez, J.A.; Masaki, Y. J. Org. Chem. 1977, 42, 1228; Chem. Abstr. 86, 72908a 34) Lewicki, J.W.; Guenther, W.H.H.; Chu, J.Y.C. J. Org. Chem. 1978, 43, 2672; Chem. Abstr. 89, 59740g 35) Klayman, D.L.; Griffin, T.S. J. Am. Chem. Soc. 1973, 95, 197; Chem. Abstr. 78, 110774y 36) Marshall, J.A.; Wuts, P.G.M. J. Am. Chem. Soc. 1978, 100, 1627; Chem. Abstr. 88, 170333v 37) Agosta, W.C.; Wolff, S. J. Am. Chem. Soc. 1977, 99, 3355; Chem. Abstr. 87, 67743j 38) Grethe, G.; Mitt, T.; Williams, T.H.; Uskokovic, M.R. J. Org. Chem. 1983, 48, 5309; Chem. Abstr. 100 7015a 39) Barrette, E.P.; Goodman, L. J. Org. Chem. 1984, 49, 176; Chem. Abstr. 100, 34748y
*For Online Consulting Only
press -F for Searching
139
40) Hamada, T.; Nishida, A.; Yonemitsu, O. J. Am. Chem. Soc. 1986, 108, 140; Chem. Abstr. 104, 51101g 41) Eur. Pat. Appl. 165,595 1985; Chem. Abstr. 104, 168761p 42) Fisher, G.H.; Schultz, H.P. J. Org. Chem. 1974, 39, 635; Chem. Abstr. 80, 95885f 43) Takanohashi, Y.; Funakoshi, H.; Akabori, S. Synthesis Commun. 1994, 24, 2733 44) Weber, J.V.; Faller, P.; Kirsch, G.; Schneider, M. Synthesis 1984, 1044 45) Yamada, K.; Fujita, T.; Yamada, R. Synlett 1998, 971 46) Zhao, X.R.; Ruan, M.D.; Fan, W.Q.; Zhou, X.J. Synth. Commun. 1994, 24, 1761 47) Back, T.G.; Birss, V.I.; Edwards, M.; Krishna, M.V. J. Org. Chem. 1988, 53, 3815 48) Engman, L.; Laws, M.J.; Malmstrom, J.,; Schiesser, C.H.; Zugaro, L.M. J. Org. Chem. 1999, 64, 6764 49) Flores, F.G.C.; Mendoza, P.G.; Mateo, F.H.; Garcia, J.I.; Gonzales, F.S. J. Org. Chem. 1997, 62, 3944 50) Chieffi, A.; Menezes, P.H.; Comasseto, J.V. Organometallic 1997, 16, 809 51) Kanda, T.; Engman, L.; Cotgreave, I.A. Powls, G. J. Org. Chem. 1999, 64, 8161 52) Dabdoub, M.J.; Dabdoub, V.A.; Comasseto, J.V. Tetrahedron Lett. 1992, 33, 2261
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
OZONIDES
2)
Ozonides are reduced by NaBH4 to the corresponding alcohol. The reduction of the ozonides of indene (1), 3-acetyl-digitoxigenin (2), cytochlasin E (3), and a number of other compounds (4-6) have been reported. Sousa and Bluhm (7) have used this reduction to cleave olefins to alcohols in good yields, with out the necessity of isolating the ozonide. When the ozonides of branched olefins are reduced with NaBH4, a mixture of alcohols is obtained which correctly, and without by products, locates the double bond position (8). Ozonide reduction with NaBH4 has been used on making anti-inflammatory derivatives of 6-oxo-1-anaphthoic acid (9) and hydroxyl-terminated low molecular weight polymers for subsequent condensation with anhydrides to form polyesters (10). The reduction of ozonides can be accomplished with sodium borohydride to form compounds such as sugars(11), Triquinane type skeleton (12) and Zaragoic Acid (13). Ozononolyis of lactams and subsequent reduction with SBH forms allylic ethers. (14)
3) 4) 5) 6) 7) 8) 9) 10) 11) 12) 13)
References: 1) Warnell, J.L.; Shriner, R.L. J. Am. Chem. Soc. 1957, 79, 3165; Chem. Abstr. 51, 15509f
*For Online Consulting Only
14)
140
Boutagy, J.S.; Thomas, R.E. Aust. J. Chem. 1971, 24, 2723; Chem. Abstr. 76, 141179w Aldridge, D.C.; Greatbanks, D.D; Turner, W.B.N. J. Chem. Soc., Chem. Commun. 1973, 551; Chem. Abstr. 79, 126471d Sundaraaraman, P.; Barth, G.; Djerassi, C. J. Org. Chem. 1980, 45, 5231; Chem. Abstr. 94, 83490z Arffin, A.A.B. J. Rubber Res. Inst. Malays. 1981, 29, 96; Chem. Abstr. 96, 2011035w Takatsuko, S.; Ikekawa, N. Tetrahedron Lett. 1983, 24, 773; Chem. Abstr. 99, 54059p Sousa, J.A.; Bluhm, A.L. J. Org. Chem. 1960, 25, 108; Chem. Abstr. 54, 15286f Hoffman, J.; Smidova, J.; Landa, S. Collect. Czech. Chem. Commun. 1970, 35, 2174; Chem. Abstr. 73, 65937n U.S. 3,644,500 1972; Chem. Abstr. 76, 140060p Japan. 73 11,235 1973; Chem. Abstr. 80, 121713v Lautens, M.; de Frutos, O.; Stammers, T.A. Tetrahedron Lett. 1999, 40, 8317 Kocovsky, P.; Dunn, V.; Gogoll, A.; Langer, V. J. Org. Chem. 1999, 64, 101 Maezaki, N.; Gijsen, H.J.M.; Suna, L.Q.; Paquette, L.A. J. Org. Chem. 1996, 61, 6685 Alcaide, B.; Casarrubios, L.; Dominguesz, G.; Sierra, M.A. J. Org. Chem. 1995, 60, 6012
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest
PEROXIDES AND HYDROPEROXIDES Jensen (1) has reported the NaBH4 reduction of some organic peroxides to be extremely rapid at room temperature. Organic peracids and peroxides formed in most ethers are also reduced. Hydrogen peroxide can react violently with sodium borohydride. Reactions with concentrated solutions have resulted in explosions. The literature describes the NaBH4 reduction of cholesterol hydroperoxide to the alcohol (2), naturally occuring terpene hydroperoxide such as neoconcinndiol hydroperoxide (3) and peroxyferolide (4), and numerous other (5-8). Rapid selective hydroperoxide reduction in the presence of keto and iodo functionalities has been reported for the 1phenylhexanone derivative formed by hydrolysis of a benziodolium cation (9). Bu
OOH O I
Bu
OH O
NaBH4
Ph
I
Ph
Peroxides formed in photosensitized oxidations of homosemibullvalene (10), stilbene derivatives (11), cyclobutane dioxetanes (12), The natural sesquiterpene
*For Online Consulting Only
141
valencene (13) and dienes of norbornane (14) have been reduced to the corresponding alcohol. Allylic hydroperoxides formed by autoxidation of methyl oleate are reduced to the corresponding allylic alcohols (15), Permitting accurate quantitative determination of their composition; previous methods were subject to significant errors. Hydroperoxides reduction has been reported in one synthetic route to the prostaglandines PGE1 and PGF1a (16). The reduction of a hydroperoxide group in an intermediate towards the synthesis of dihydroxyvitamin D3 has been accomplished with sodium borohydride. (17) Sodium borohydride in MeOH have reduced peroxides to diols. (18) References: 1) Jensen, E.H. “ A Study on Sodium Borohydride”, Nyt. Nordisk Forlag Arnold Busck, Copenagen 1954 (out of print); Chem. Abstr. 49, 13010a 2) Kulig, M.J.; Smith, L.L. J. Org. Chem. 1974, 39, 3398; Chem. Abstr. 82, 53949r 3) Howard, B.M.; Fennical, W.; Finer, J.; Hirotsu, K.; Clardy, J. J Am. Chem. Soc. 1977, 99, 6440; Chem. Abstr. 87, 184722n
Rohm and Haas : the Sodium Borohydride Digest
4) Doskotch, R.W.; El-Feraly, F.S.; Fairchild, E.H.; Haung, C.T. J. Org. Chem. 1977, 42, 3614; Chem. Abstr. 87, 180643q 5) Johnson, W.S.; Dumas, D.J.; Berner, D. J. Am. Chem. Soc. 1982, 104, 3510; Chem. Abstr. 97, 24076h 6) Adam, W.; Hannemann, K.; Wilson, R.M. J. Am. Chem. Soc. 1984, 106, 7646; Chem. Abstr. 102, 5437g 7) Bull, A.; Nigro, N.D. et al. Cancer Res. 1984, 44, 4924; Chem. Abstr. 102, 19325f 8) Van Kuijk, F.J.G.M.; Thomas, D.W.; Stephens, R.J.; Dratz, E.A.; J. Free Radicals Biol. Med. 1985, 1, 215; Chem. Abstr. 104, 48268m 9) Beringer, F.M.; Ganis, P.; Avitabile, G.; Jaffe, H. J. Org. Chem. 1972, 37, 879; Chem. Abstr. 76, 126504e 10) Sakai, M.; Harris, D.L.; Winstein, S. J. Org. Chem. 1972, 37, 2631; Chem. Abstr. 77, 100898g 11) Saito, I.; Matsuura, T. Chem. Lett. 1972, 1169; Chem. Abstr. 78, 83937v 12) Rigaudy, J.; Capdevielle, P.; Maumy, M. Tetrahedron Lett. 1972, 4997; Chem. Abstr. 78, 123619b
*For Online Consulting Only
press -F for Searching
142
13) Schaffer, G.W.; Eschinasi, E.H.; Purzycki, K.L.; Doerr, A.B. J. Org. Chem. 1975, 40, 2181; Chem. Abstr. 83, 97599b 14) Jefford, C.W.; Rimbault, C.G. J. Org. Chem. 1978, 43, 1908; Chem. Abstr. 88, 189637u 15) Garwood, R.F.; Khambay, B.P.S.; Weedon, B.C.L.; Frankel, E.N. J. Chem. Soc., Chem. Commun. 1977, 364; Chem. Abstr. 87, 183915r 16) U.S. 3,953,499 1976; Chem. Abstr. 86, 16342z 17) Linker, T.; Frohlich, L. J. Am. Chem. Soc. 1995, 117, 2694 18) Carless, H.A.J.; Oak, O.Z. Tetrahedron Lett. 1989, 30, 1719
Rohm and Haas : the Sodium Borohydride Digest
III. INORGANIC APPLICATIONS A. Inorganic Reductions Alembic: 6 Sodium borohydride is a tremendously versatile reducing agent and ligand for inorganic reactions, as shown by the wealth of literature which as appeared in the last 50 years. Some excellent reviews have appeared in the literature and are recommended (16). In addition Rohm and Haas over the past 30 years has complied and regularly updates a full bibliographic database pertaining to the reduction of metals. We are prepared to answer all questions relating to the application of borohydrides and amine boranes for the reduction of metals. METAL CATION REDUCTIONS Alembic: 6 A substantial number of metal cations are reduced by borohydride in protic or aprotic solvent. Reduction can be classified according to the product obtained. The products may be a lower valence compound, the free element, a volatile hydride or a
*For Online Consulting Only
press -F for Searching
143
metal “boride’. These reductions are summarized in Periodic Table form in Figure 11. In addition to a references cited in this table, the following publications are significant: - “Catalytically Active Borohydride-Reduced Nickel and Cobalt Systems” (7), - “Reactions of Sodium Tetrahydroborate and Cyanotrihydroborate with Divalent Cobalt, Nickel, Copper, Palladium and Platinum in the Presence of Triphenyl Phosphines” (8) - Hydride Complexes of iron (II) and ruthenium (II)” (9) - The Mechanism of the reduction of the Inorganic compounds with alkali Metal Borohydride” (10), - “Sodium tetrahydroborate as a new reagent in the Systematic Course of Qualitative Analysis I. Reduction of Sodium Tetrahydroborate with metal cations” (11). Reduction of toxic or valuable heavy metals in process waste streams is an important industrial application for sodium borohydride.(12-14). Quantitative reduction and recovery of mercury (15- 18), lead (19), silver (20, 21), gold (22, 23), copper (13,14), and platinum group metals (24-26) can be accomplished. The use of NaBH4 in the development process for color reversal photographic film is well documented (27-29)
Rohm and Haas : the Sodium Borohydride Digest
Cation reductions with NaBH4 are being used commercially in the area of electroless plating, particularly of nickel, on both metallic and non-metallic substrates. Practical aspects of this application have been published (30, 31), and extended plating bath life and ease of regeneration have been cited as advantages. These coatings contain up to 5% boron and, when annealed, consist of a dispersion of Ni3B in a nickel matrix (32) which provides a wear resistant finish of superior hardness. Cobalt (33, 34), gold (35,36), copper (37, 38) and iridium (39) have also been plated by NaBH4 reduction. The copper deposits, on plating glass, are used in solar control windows having reflective bronze finish. Russian publications report NaBH4 reduction of electroless plating of silver (40), iron (41), palladium (42), platinum (43), and ruthenium (44). NaBH4 is also reported to be effect in pretreating or sensitizing noncatalytic substrates for subsequent electroless plating (45, 46, 47). A recent patent has been issued for a process for electroless plating of polymer or resins with Ag, Co, Ru, Ce, Fe, Mn, Ni, Rh, and/or V. (48) Several metal compounds such as cobalt chloride (49) chromium oxide, Cr2O3 (50 44), molybdenum and tungsten oxides (51 45) and molybdenum chloride (52 46), have been reduced by
*For Online Consulting Only
press -F for Searching
144
heating these compounds together with sodium borohydride in the absence of any solvent to produce metal powders. NaBH4 reduction has also been applied to the manufacturing of amorphous metal alloy (53), extremely fine metal powders of copper (54 55), silver (56), ruthenium (57), gold (58, 59), Pt (60), Fe (61) and nickel or cobalt (62), and magnetic metal powders for tape recording media (63, 64, 65, 66). Other recent applications include boiler scale removal (67), the preparation of methanol reforming catalysts (68), The preparation of a cobalt catalyst for the hydrogenantion of glucose to sorbetol (69) and of catalytic converters for automobile exhausts gases (70). Reacting metal salts and sodium borohydride at elevated temperatures have formed mixed metal alloys. (71- 80) The kinetics of the reaction of the ammonium ion with the borohydride anion in liquid ammonia to produce ammonia-borane, NH3BH3, has been reported (81). The borohydride reduction of nanogram quantities of arsenic (82-87), antimony (82-84, 87), bismuth (82, 83), tin (82-87), germanium (84) mercury (86), tellurium (86), selenium (82, 83), indium and thallium (88) and lead (86, 89) to produce volatile hydrides for detection by atomic absorption, gas chromatography and emission spectroscopy has been widely reported and is extensively used by analysts. Elemental powered selenium and sodium borohydride react rapidly in water or ethanol to give either NaHSe or
Rohm and Haas : the Sodium Borohydride Digest
Na2Se2 (90). The reduction of Sb2O3 with sodium borohydride in ethylene glycol produces a finely divided antimony powder useful as a catalyst for polyester manufacture (91). The mechanism of the reduction of arsenic (III) chloride and oxide and the preparation of arsine by the borohydride reduction of these compounds has been reported (92). METAL ANION REDUCTIONS Alembic: 6 An Important industrial use of sodium borohydride is the reduction of the bisulfite anion to produce dithionite (hydrosulfite) anion (93, 94):
*For Online Consulting Only
press -F for Searching
145
BH4- + 8 HSO3- + H+ Æ 4 S2O42- + H3BO3 + 5 H2O
Hydrosulfite (S2O4)2- generated by NaBH4 reduction of tetravalent sulfur species is widely applied industrially in bleaching mechanical pulps (95, 96). Other anions which have been studied systematically, mainly in the USSR, include Rhenium dioxide and perrhenate to Re (V), (III), or (II) (97,98); Osmium tetraoxide to Os (VII), (VI), and (IV) (99); Pertechneate to Tc. Figure 11 : Studies of Na BH4 Reductive Strength
Rohm and Haas : the Sodium Borohydride Digest
*For Online Consulting Only
press -F for Searching
146
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
(0) (100); Vanadate to V (III) and (IV) (101,102); Molybdate to Mo (V) and “molybdenum blue” (103, 104); Tungstate to W (IV) and tungsten blue (105, 106); Permanganate to MnO2 and Mn (II) (107); hexacyanoferrate to Fe (II) (108, 109); and iodine (in DMF) to NaI = B2H6, BH2I, BH2I2 and B2H5I (110, 111). The utilization of sodium borohydride as an efficient energy storage media has been demonstrated. The 8 electron electrochemical oxidation of sodium borohydride in aqueous alkaline solution produced specific energies of greater then 180 Wh/kg (based on total fuel wt.) and power densities greater then 20mW/cm2 at room temp and greater then 60mW/cm2 at 70 degree C. (112)
5) Ephritikhine, M. Chem. Rev. 1997, 97, 2193 6) Klabunde, K.J.; Stark, J.V.; Koper, O.; Mohs, C.; Khalell, A.; Glavee, G.; Zhang, D.; Sorensen, C.M.; Hadjipanaylis, G.C. Nanophase Materials, 1994, 1 7) Wade, R.C.; Holah, D.G.; Hughes, A.N.; Hui, D.C. Catal. Rev. Sci. Eng. 1976, 14, 2111; Chem. Abstr. 86, 22275w 8) Holah, D.G.; Hughes, A.N.; Hui, B.C.; Wright, K. Can. J. Chem. 1974, 52, 2990; Chem. Abstr. 81, 144867h 9) Peet, W.P.; Gerlak, D.H. Inorg. Synth. 1974, 15, 38; Chem. Abstr. 81, 130285e 10) Hanzlik, J. Chem. Listy 1973, 67, 1239; Chem. Abstr. 80, 66215g 11) Khain, V.S.; Chazov, M.M.; Krivokorytova, L.A. Tr. Tyumen. Ind. Inst. 1972, 241; Chem. Abstr. 82, 132525c 12) Jula, T.F. Process Eng. 1975 123; Chem. Abstr. 83, 151770r 13) Cook, M.M.; Lander, J.A. Pollut. Eng. 1981, 13, 36; Chem. Abstr. 967, 168042w 14) Ulman, J.A. Spec. Chem. 1985, 5, 27; Chem. Abstr. 103, 128490x 15) U.S. 3,736,253 1973; Chem. Abstr. 79, 45540y 16) U.S. 3,764,528 1973; Chem. Abstr. 80, 30452t 17) U.S. 3857,704 1974; Corresponding to Brit. 1,368,966 1974; Chem. Abstr. 82, 89846u 18) Ger. Offen. 3,335,127 1985; Chem. Abstr. 102, 207132q
References: 1) James, D.B. Wallbridge, M.G.H. Prog. Inorg. Chem. 1970, 11, 99; Chem. Abstr. 73, 41276v 2) Marks, T.J.; Kolb, J.R. Chem. Rev. 1977, 77, 263; Chem. Abstr. 86, 140116t 3) Kadlec, V.; Kadlecova, H; Masek, J. Chem. Listy 1976, 70, 673; Chem. Abstr. 85, 136308u 4) Jula, T.F. “Inorganic Reductions with sodium borohydride” Ventron Corp. 1974
*For Online Consulting Only
147
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
19) Ger. Offen. 2,408,995 1974; Chem. Abstr. 82, 160007d 20) U.S. 4,279,644 1981; Chem. Abstr. 95, 223522j 21) Jpn. Kokai Tokkyo koho 86 34,125 1986; Chem. Abstr. 104, 228180k 22) Jpn. Kokai, Tokkyo Koho 85, 159, 134 1985; Chem. Abstr. 104, 8756n 23) McPartland, J. S.; Bautista, R. G. Met. Sep. Technol. Beyond 2000: Proc. Symp., 1999, 105 24) U.S. 4,319,923 1982; Chem. Abstr. 96, 203153g 25) Jpn. Kokai Tokkyo Koho 85, 251, 233 1985; Chem. Abstr. 104, 190311p 26) U.S. 5,304,233 1994 27) U.S. 2,984, 567 1961; Chem. Abstr. 55, 21936a 28) U.S. 3,554, 748 1971; corresponds to Fr. 1,548, 122 1968; Chem. Abstr. 71, 86594x 29) U.S. 4,259,114 1981; Chem. Abstr. 95, 52631n 30) Lang, K. Electroplating Metal Finishing 1966, 19, 86; Chem. Abstr. 65, 10252h 31) Neiderpruem, H.; Klein, H.G. Metal Finishing J. 1971, 17, 18; Chem. Abstr. 75, 37956r 32) Matusuoka, M. Hayashi, T. Denki Kagaku 1978, 46, 163; Chem. Abstr. 89, 93640j
33) Valsiuniene, J.; Prokopoikas, A. Liet. TSR Mokslu Akad. Darb., Ser. B 1972, 1, 19; Chem. Abstr. 77, 78564w 34) U.S. 3,096,182 1963; Chem. Abstr. 59, 8443h 35) Okinaka, Y. J. Electrochem. Soc. 1973, 120, 739; Chem. Abstr. 79, 26529k 36) U.S. 3,697,296 1972; Chem. Abstr. 78, 19607k 37) U.S. 3,671,291 1972; Chem. Abstr. 77, 78794w 38) U.S. 4,082,898 1978; Chem. Abstr. 89, 63663b 39) Jpn. Kokai Tokkyo Koho JP 11131249 A2 19990518 1999; Chem. Abstr. 130, 341516 40) Valsiuiene, J. Prokopchik, A.Y.; Kaskelis, A. Liet. Tsr Mokslu Akad. Darb. Ser B 1975, 6, 3; Chem. Abstr, 111619h 41) Valsiuniene, J.; Zielys, H.; Prkopchik, A.Y. Liet. Tsr Mokslu Akad. Darb. Ser B 1976, 1, 27; Chem. Abstr. 85, 164326s 42) Valsiuniene, J.; Prokopchik, A.Y.; Kaskelis, A. Liet. Tsr Mokslu Akad. Darb. Ser B 1976, 4, 25; Chem. Abstr. 86, 125406u 43) Valsiuniene, J.; Vinkevicius, J.; Prokopchik, A.Y. Liet. Tsr Mokslu Akad. Darb. Ser B 1976, 5, 25; Chem. Abstr. 87, 27130a
*For Online Consulting Only
148
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
44) Valsiuniene, J. Norgailaite, A. Issled. Obl. Elektroosazhdeniya Met. Resp. Konf. Elektrokhim. Lit. SSR, 14th 1976, 215; Chem. Abstr. 87, 27136g 45) U.S. 3,962,494 1976; Chem. Abstr. 85, 165396b 46) U.S. 3,993,801 1976; Chem. Abstr. 86, 94685c 47) U.S. 4,323,594 1982; Chem. Abstr. 97, 7563x 48) Eur. Pat. Appl. EP 913498 A1 19990506, 1999; Chem. Abstr. 130, 300137 49) Sterlyadkena, Z.K.; Alekseeva, L.S.; Maltseva, N.N. Zh. Neorg. Khim. 1973, 18, 260; Chem. Abstr. 78, 91990x 50) Alekseeva, L.S. et. al. Zh. Neorg. Khim. 1975, 20, 2339; Chem. Abstr. 83, 201393t 51) Alekseeva, L.S. et. al. Zh. Neorg. Khim 1976, 21, 277; Chem. Abstr. 84, 115375c 52) Alekseeva, L.S. et. al. Zh. Neorg. Khim 1977, 22, 1695; Che. Abstr. 87, 61817q 53) U.S. 4,585,617 1986; Che. Abstr. 105, 47448d 54) Jpn. Kokai Tokkyo Koho 85, 86, 203 1985, Che. Abstr. 103, 900911v 55) Qiu, S.; Dong, J.; Chen, G. J. Colloid Interface Sci., 1999, 216, 230
56) Shirtcliffe, N.; Nickel, U.; Schneider, S. J. Colloid Interface Sci. 1999, 211, 122; Chem. Abstr. 130, 242696 57) Jpn. Kokai. Tokkyo Koho, 1999; JP 11031417 A2 19990202; Chem. Abstr. 130, 155069 58) Chen, S.; Kimura, K. Langmuir, 1999, 15,1075-1082 ; Chem. Abstr. 130, 213995 59) Bronstein, L. M.; Platonova, O.A.; Yakunin, A. N.; Yanovskaya, I.M.; Valetsky, P. M.; Dembo, A. T.; Obolonkova, E. S.; Makhaeva, El. E.; Mironov, A. V.; Khokhlov, A.R. Colloids Surf., A 1999, 147, 221-231 ; Chem. Abstr. 130, 253037 60) Dykman, L. A.; Lyakhov, A.A.; Bogatyrev, V. A.; Shchyogolev, S. Yu. Colloid J. 1998, 60, 700-704 ; Chem. Abstr. 130, 144556 61) Wang, C. Y.; Chen, Z. Y.; Cheng, B.; Zhu, Y. R.; Liu, H. J. Mater. Sci. Eng., B, 1999, B60, 223 62) Jpn Kokai Tokkyo Koho 84, 160, 539 1984; Chem. Abstr. 102, 29286h 62) U.S. 4,394,160 1983; Chem. Abstr. 99, 98069w 63) Jpn. Kokai Tokkyo Koho 86 48,503 1986; Chem. Abstr. 105, 47074d 64) Duxin, N.; Pileni, M. P.; Wernsdorfer, W.; Barbara, B.; Benoit, A.; Mailly, D. Langmuir
*For Online Consulting Only
149
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
65) Rittenberg, Durrell K.; Sugiura, Ken-ichi; Sakata, Yoshiteru; Guzei, Ilia A.; Rheingold, Arnold L.; Miller, Joel S. Chem.--Eur. J. 1999, 1874 66) U.S. 4,610728 1986; Chem. Abstr. 105, 230807j 67) Jpn. Kokai Tokkyo Koho 86 50,639 1986; Chem. Abstr 105, 45828d 68) Li, H.; Li, H.; Wang, W; Deng, J.-F Chem. Lett. 1999, 629 70) Jpn. Kokai Tokkyo Koho 84, 160,539 1984; Che. Abstr. 102, 31299 71) Stolk, J.; Manthiram, A Mater. Sci. Eng., B, 1999, B60, 112-117 72) Pan, H.; Chen, Y.; Chen, C.; Wang, Q. Jinshu Xuebao, 1999, 35, 300 Chem. Abstr. 130, 314363 73) Chen, M.; Nikles, D. E. J. Appl. Phys. 1999, 85 Pt. 2B, 5504; Chem. Abstr. . 131, 21468. 74) Mitov, M.; Popov, A.; Dragieva, I. Colloids Surf., A 1999, 149; Chem. Abstr. 1999, 243226 75) Seita, M.; Kusaka, M.; Nawafune, H.; Mizumoto, S Plat. Surf. Finish. 1999, 86, 62; Chem. Abstr. 130, 314985
76) Mitov, M.; Popov, A.; Dragieva, I J. Appl. Electrochem. 1999, 29, 59; Chem. Abstr. 130, 288352 77) Cassagneau, Thierry; Fendler, Janos H J. Phys. Chem. B 1999, 103, 1789; Chem. Abstr. 130, 257713 78) Forster, G. D.; Fernandez Barquin, L.; Pankhurst, Q. A.; Parkin, I. P. J. Non-Cryst. Solids 1999, 244, 44; Chem. Abstr. 130, 284883 79) Osvath, P.; Sargeson, A.M.; McAuley, A.; Mendelez, R.E.; Subramanian, S.; Zaworotko, M. J.; Broge, L. Inorg. Chem. ACS ASAP 80) Rakovich, E. V.; Sviridov, V. V Vestsi Nats. Akad. Navuk Belarusi, Ser. Khim. Navuk 1998, 9; Chem. Abstr. 130:314694 81) Broiggs, T.S. Jolly, W.L. Inorg. Chem. 1975, 14, 2267; Chem. Abstr. 83, 137450e 82) Schmidt, F.J.; Royer, J.L.; Muir, S.M. Anal. Lett. 1975, 8, 123; Chem. Abstr. 83, 212178c 83) Schmidt, F.J.; Royer, J. Anal. Lett. 1973, 6, 17; Chem. Abstr. 78, 92121b 84) Kadeg, R.D.; Christian, G.D. Anal. Chim. Acta 1977, 88, 117; Chem. Abstr. 86, 182495w 85) Braman, R.S. et. al. Anal. Chem. 1977, 49, 621; Chem. Abstr. 87, 34003q
*For Online Consulting Only
150
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
86) Dujmovic, M. GIT Fachz. Lab. 1977, 21, 761; Chem. Abstr. 87, 21619f 87) Frolov, I.A; kulakov, S.I.; Yakush, G.M. Zh. Prikl. Khim. 1977, 50, 2561; Che. Abstr. 88, 42199u 88) Yan, D.; Yan, Z.; Cheng, G.; Li, A. Talanta 1984, 31, 133; Chem. Abstr. 100, 150274q 89) Vijan, P.N.; Wood, G.R. Analyst 1976, 101, 966; Chem. Abstr. 86, 182500u 90) Klayman, D.; Griffin, T.S. J. Am. Chem. Soc. 1973, 95,197; Chem. Abstr. 78, 110774y 91) Japan. Koaki 74 15,137 1974; Chem. Abstr. 82, 17737m 92) Kulakov, S.I. et. al. Zh. Neorg. Khim. 1974, 19, 3239; Chem. Abstr. 82, 67604m 93) Panson, G.S.; Weil, C.E. J. Inorg. Nucl. Chem. 1960, 15, 184; Chem. Abstr. 55, 5216b 94) Luner, P. LaPlaine, R. Wade, R. Pulp Paper Mag. Canada 1964, 65, T-101 95) Gerrie, J.W. Pulp Paper Mag. Canada 1974, T251; Chem. Abstr. 81, 17676b
96) U.S. 5,129987 1992; U.S. 5,094833 1992; U.S. 5188807, 1993; U.S. 5,391261 1995; 5,336479 1994; 5,429716, 1995) 97) Khain, V.S.; Antsygina, N.N. Zh. Neorg. Khim. 1977, 22, 2987; Chem. Abstr. 88, 31322c 98) Pacer, R.A. J. Inor. Nucl. Chem. 1973, 35, 1375; Chem. Abstr. 78, 131585c 99) Khain, V.S. Fomina, E.V.; Volkov, A.A. Zh. Neorg. Khim. 1977, 22, 2987; Chem. Abstr. 88, 31322c 100) Pacer, R.A. J. Inorg. Nucl. Chem. 1976, 38, 817; Chem. Abstr. 84, 188858x 101) Andreev, F.I.; Khain, V.S. Zh. Neorg. Khim. 1976, 21, 1228; Chem. Abstr. 85, 56030g 102) Khain, V.S.; Andreeev, F.I.; Kinet. Katal. 1977, 18, 267; Chem. Abstr. 86, 128068w 103) Khain, V.S.; Andreeev, F.I. Neorg. Khim. 1978, 23, 977; Chem. Abstr. 89, 52634s 104) Andreev, F.I.; Khain, V.S. Zh. Obshch. Khim. 1975, 45, 2099; Chem. Abtsr. 86, 128068w 105) Khain, V.S.; Andreev, F.I. Zh. Obshch. Khim. 1977, 47, 715; Chem. Abstr. 87, 15322b 106) Khain, V.S.; Andreev, F.I. Zh. Neorg. Khim. 1977, 22, 534; Chem. Abstr. 86, 132741c
*For Online Consulting Only
151
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
107)
116) Waller, Sr. M.C. “Inorganic Chemistry of borohydride” Metal hydride inc. 117) Warburton, C.D.; Przbylowicz, E.P. Phot. SSCci. Eng. 1966, 10, 86; Chem. Abstr. 64, 15226e 118) Shah, A.R.; Padma, D.K.; Murthy, A.R.V. Indian J. Chem. 1971, 9, 885; Chem. Abstr. 75, 136669f 119) Castellani-Bisi, C. Ann. Chim. 1959, 49, 2057; Chem. Abstr. 54, 17137b 120) Chaikin, S.W. Anal. Chem. 1953, 25, 831; Chem. Abstr. 47, 7371g 121) Andreev, F.I.; Tsivelev, R.P.; Khain, V.S. Zh. Neorg. Khim. 1978, 23, 2847; Chem. Abstr. 89, 225385s 122) Sterlyadkina, Z.K.; Alekseeva, L.S.; Mikheeva, V.I. Zh. Neorg. Khim. 1969, 14, 2677; Chem. Abstr. 72, 38350p 123) Alekseeva, L.S. Zh. Neorg. Khim. 1975, 20, 2339; Chem. Abstr. 83, 201393t 124) Freund, T.; Neunkle, N. J. Am. Chem. Soc. 1961, 83, 3378; Chem. Abstr. 56, 1125d 125) Freund, T. J. Inorg. Nucl. Chem. 1959, 9, 246; Chem. Abstr. 53, 16665h 126) Mochalov, K.N.; Khain, V.S. Zh. Fiz. Khim. 1965, 39, 1960; Chem. Abstr. 63, 15846b
108) 109) 110) 111) 112) 113) 114) 115)
Khain, V.S.; Maretynova, V.F.; Zh. Neorg. Khim. 1978, 23, 680; Chem. Abstr. 88, 181734c Khain, V.S.; Fomina, E.V.; Volkov, A.A. Zh. Obshch. Khim. 1977, 47, 1929; Chem. Abstr. 87, 189975g Giniyatullin, N.G.; Kargin, Y.M. Izv. Vyssh. Uchebn. Zaved., Khim. Tekhnol. 1976, 19, 1668; Chem. Abstr. 86, 64862t Khain, V.S.; Val’kova, V.P.; Kotelevets, E.S. Zh. Neorg. Khim. 1977, 22, 338; Chem. Abstr. 86, 132740b Khain, V.S.; Val’kova, V.P. Zh. Obshch. Khim 1977, 47, 961; Chem. Abstr. 87, 29619r Amendola, S. C.; Onnerud, P.; Kelly, M. T.; Petillo, P. J.; Binder, M. Proc. - Electrochem. Soc., 1999, 98 , 47 Gardiner, J.A. Collat, J.W. J. Am. Chem. Soc. 1965, 87, 1692; Chem. Abstr. 62, 13899b Gardiner, J.A. Collat, J.W Inorg. Chem. 1965, 4, 1208; Chem. Abstr. 63, 6610e Jolly, W.L.; J. Am. Chem. Soc. 1961, 83, 335; Chem. Abstr. 55, 12126c
*For Online Consulting Only
152
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
127) Freitag, W.O.; Sharp, T.A.; Baltz, A.; Suchodolski, V. J. Applied Phys. 1979, 50, 7801; Chem. Abstr. 92, 87038q 128) Schlesinger, H.I. et al. J. Am. Chem. Soc. 1953, 75, 199; Chem. Abstr. 47, 3741h 129) McBride, D.G.; Vlasak, G.P. J. Electrochem. Soc. 1971, 118, 2055; Chem. Abstr. 76, 62788r 130) Pratt, J.M.; Swinden, G. J. Chem. Soc., Chem. Commun. 1969, 1321; Chem. Abstr. 72, 47951 131) Paul, R.; Buisson, P.; Joseph, N. Ind. And Eng. Chem. 1952, 44, 1006; Chem. Abstr. 46, 9960e 132) Thonnart, P. Lenfart, P.; Legas, C.C. R. Acad. Sci. Paris 1964, 258, 5207 133) Hofer, L.J.E.; Shultz, J.F.; Panson, R.D.; Anderson, R.B. Inorg. Chem. 1964, 3, 1783; Chem. Abstr. 62, 4886b 134) Brown, C.A. J. Org. Chem. 1970, 35, 1900; Chem. Abstr. 73, 29374t 135) Waller, M.C.; Miniatas, B.O.; Hohnstedt, L.F. Anal. Chem. 1965, 37, 1163; Chem. Abstr. 10641c 136) Mochalov, K.N.; Bashkirova, T.I. Zavod. Lab. 1969, 35, 795; Chem. Abstr. 72, 74415x
137) Prokopoikas, A.; Sakalauskiene, J. Liet. Tsr Mokslu Akad. Darb., Ser B. 1971, 117; Chem. Abstr. 76, 63968m 138) Rozovskis, G. Issled. Obl. Osazhdeniya Metal., Mater. Respub. Konf. Electrokhim., Litov SSR, 11th 1971, 133; Chem. Abstr. 77, 23789t 139) Piper, T.S.; Wilson, K.M. J. Inorg. Nucl. Chem. 1957, 4, 22; Chem. Abstr. 51, 7924e 140) Maklen, E.D. J. Chem. Soc. 1959, 1989; Chem. Abstr. 53, 14805g 141) Jolly, W.L. et. al. J. Inorg. Nucl. Chem. 1960, 14, 190 142) Gunn, S.R.; Jollly, WL.; Green, L.G. J. Phys. Chem. 1960, 64, 1334; Chem. Abstr. 55, 8026f 143) Mochalov, K.N. et. al. Dokl. Akad. Nauk. SSSR 1966, 64, 1334; Chem. Abstr. 64, 17009f 144) Mochalov, K.N.; Polovnyak,V.K.; Groisberg, A. T. Izv. Vyssh. Ucheb. Zaved., Khim,. Khim. Tekhnol. 1973, 16, 1115; Chem. Abstr. 79, 111314f 145) Alekseeva, L.S. et. al. Zh. Neorg.Khim. 1976, 21, 277; Chem. Abstr. 84, 115375c 146) Brown, H.C.; Brown, C.A. J. Am. Chem. Soc. 1962, 84, 1493; Chem. Abstr. 57, 111b
*For Online Consulting Only
153
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
147) Mochalov, K.N.; Ostryakova, T.A.; Tremasov, N.V. Tr. Kazan. Khim. Teknol. Inst. 1969, 40, 186; Chem. Abstr. 75, 44502t 148) Khain, V.S.; Volkov, A.A. Zh. Prikl. Khim. 1983, 56, 663; Chem. Abstr. 98, 226838q 149) Borgonostesev, A.S.; Timofeeva, G.P. Tr. Kazan. Inzh. Stroit. Inst. 1967, 142; Chem. Abstr. 74, 37951q 150) Svata, M..; Jindra, J. Colllect. Czech. Chem. Commun. 1970, 35, 692; Chem. Abstr. 72, 95972s 151) U.S.S.R. 269, 670 1970; Chem. Abstr. 73, 58794k 152) Schaeffer, G.W.; Emilius, M. J. Am. Chem. Soc. 1954, 76, 1203; Chem. Abstr. 48, 6303h 153) Evans, D.H. Anal. Chem. 1964, 36, 2435; Chem. Abstr. 62, 3399f 154) Zorin, A.D.; Frolov, I.A.; Morozova, T.V. Sh. Obshch. Chim. 1972, 42, 900; Chem. Abstr. 77, 83043e 155) Khain, V.S.; Kotelevets, E.S. Zh. Neorg. Khim. 1982, 27, 1199; Chem. Abstr. 97, 32674s
156) Lyttle, D.A.; Jensen, E.H.; Struck, W.A. Anal. Chem. 1952, 24, 1843; Chem. Abstr. 47, 1005h 157) Mochalov, K.N.; Gilmanashin, G.G.; Giniyatullinm, N.G.; Polovnyak, V.K. Tr. Kazan. Khim. Tekhnol. Inst. 1969, 40, 143; Chem. Abstyr. 75, 14489b 158) Khain, V.S.; Zhomova, M.I.; Andreev, F.I. Zh. Neorg. Khim. 1985, 30, 360; Chem. Abstr. 102, 142133u 159) Khain, V.S. Zh. Prikl. Khim. 1980, 53, 2745; Chem. Abstr. 94, 149364v 160) Volkov, A.A.; Khain, V.S. Zh. Anal. Khim. 1982, 37, 876; Chem. Abstr. 97, 103483s 161) Marshall, E.D.; Widing, R.A. U.S.A.E.C. Report AECD-2914 1950 162) Romain, P.; Merland, R. Laubie, H. Bull. Soc. Pharm. Bordeaux 1954, 92, 131; Chem. Abstr. 50, 722e
*For Online Consulting Only
154
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
B. Organometallic
organophosphorus ligands has been reported for iron (2-4), ruthenium (2) and cobalt (5). Examples of NaBH4 reduction to lower valent metal complexes are the octaethylporphyrin complexes of Rh (I) (6) and Fe (II) (7,8) made from the corresponding M(III) complex chlorides, and the bis-dehyrocorrin complex of Co(I) made from the corresponding dicyanocobalt (III) complex (9). The most familiar type of demetallation or cleavage of organometallics by NaBH4, is demercuration, which is covered in a separate section. The analogous reduction of organothallium compounds has also been reported (10,11). Other cleavages include those of serinato copper (II) complexes (12), a tetracarbonylallyliron cation (13), dimeric cienyl rhodium complexes (14), and cephem-π-allyl palladium dichloride (15). Complex formation and reduction in the last instance is utilized to isomerize 2-cephenms to 3-cephems. Published examples involve cleavage of magnesium and lead macrocycles (16), a palladium pyrazinoindole complex (17), silver and copper porphyrins (18), and heterocyclic amino acid complexes of copper and nickel (19). The conversion of organometallic halides to the corresponding hydride or hydride halide, by reduction with NaBH4 is widely used and has been applied to complexes of
The rapid growth of organometallic chemistry in recent years has given rise to numerous applications of sodium borohydride’s reducing capabilities. From a survey of literature citations using NaBH4 in this specialized field, it quickly becomes apparent that, in general, five major types of reactions are involved: initial formation of organometallic compounds and complexes, reduction to lower valent metal compounds, demetallation or cleavage or organometallics to the metal and organic species, conversion of organometallic halides to the corresponding hydride or hydride halide, and reduction of organometallic cations to neutral species. The formation of organometallics via NaBH4 reduction is typified by the formation of cobalt (II) thiol complex catalysts where the thiol ligands are derived from amino acids such as serine, cysteine and cysteamine (1); these catalysts are effective in the reduction of acetylene. The use of NaBH4 in the synthesis of hydridometal complexes with
*For Online Consulting Only
155
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
chromium (20), iron (21), cobalt (22), nickel (23,24), molybdenum (25), tungsten (25), tin (26,27), ruthenium (28), rhodium (29,30) palladium (23), osmium (31,32), platinum (29,33,34), and iridium (35). The generation of organometallic hydrides has also been used on the analytical determination of organometallic species in various matrices, e.g. Ge (36), Sn (37) and Pb (38). Organometallic cations are often reduced by NaBH4 to give neutral organometallic compounds, as in the cases of Mo (39), Mn (40), Re (41), Ru (42), Co (43), and Fe (44). The preparation of several hydrogenantion catalysts bound to polymers has been reported, including palladium (45), rhodium (45,46), iridium (47), and others (48). NaBH4 reduction of metal carbonyls, followed by acidification, has been used as a general synthetic method for transition metal hydrido carbonyl clusters (49). Other used include a commercial nickel phosphine catalyst for ethylene oligomerization to linear alpha-olefins (50-53), the reduction of optically
pure deuterated amino acid complexes of Co (III) to provide optically pure amino acids without loss of deuterium (54), an active homogeneous molybdenum carbonyl catalyst for the water gas shift reaction (55), and the generation of spent hydroformylation catalysts (56).
*For Online Consulting Only
References: 1) Sugiura, Y.; Kikuchi, T.; Tanaka, H. J. Chem. Soc., Chem. Commun. 1977, 795 2) Gerlach, D.H.; Peet, W.G.; Muetterties, E.L. J. Am. Chem. Soc. 1972, 94, 4545; Chem. Abstr. 77, 62114p 3) Dapporto, P.; Fallani, G.; Midollini, S.; Sacconi, L. J. Am. Chem. Soc. 1973, 95, 2021; Chem. Abstr. 78, 13154k 4) Giannoccaro, P.; Sacco, A. Inorg. Synth. 1977, 17, 69; Chem. Abstr. 88, 12113d 5) Carriedo, C.; Gomez-Sal, P. et. al. J. Organomet. Chem. 1986, 301, 79; Chem. Abstr. 104, 179029g 6) Ogoshi, H.; Sntsune, J.; Tyoshida, Z. J. Am. Chem. Soc. 1977, 99, 3869; Chem. Abstr. 887, 135837v 7) Dolphin, D.; Sams, J.R.; Tsin, T.B.; Wong, K.L. J. Am. Chem. Soc. 1976, 98, 6970 8) Jpn. Kokai Tokkyo Koho 78, 112, 900 1978; Chem. Abstr. 90, 121679v
156
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
9) Murakami, Y.; Aoyama, Y.; Nakanishi, S.; Chem. Lett. 1977, 991;Chem. Abstr. 87, 126495e 10) Bach, R.D.; Holubka, J.W. J. Am. Chem. Soc. 1974, 96, 7814; Chem. Abstr. 82, 16203x 11) Uemura, S.; Miyoshi, M.: Tara, H.; Okano, M.; Ichikawa, K. J. Chem. Soc., Chem. Commun. 1976, 218; Chem. Abstr. 85, 46802w 12) O’Conner, M.J.; Smith, J.F.; Teo, S. Aust. J. Chem. 1976, 29, 375; Chem. Abstr. 84, 180114f 13) Pearson, A.J. Aust. J. Chem. 1976, 29, 1841; Chem. Abstr. 86, 16771p 14) Eaton, P.E.; Patterson, D.R. J. Am. Chem. Soc. 1978, 100, 2573; Chem. Abstr. 89, 43537k 15) Jpn. Kokai 77 105,192 1977; Chem. Abstr. 88, 105372t 16) Mandal, S.K.; Nag, K.J. J. Org. Chem. 1986, 51, 3900; Chem. Abstr. 105, 1724435y 17) Hegedus, L.S.; Mulhern, T.A.; Asada, H. J. Am. Chem. Soc. 1986, 108, 6224; Chem. Abstr. 105, 172406q 18) Cowen, J.A/; Sanders, J.K.M. Tetrahedron Lett. 1986, 27, 1202; Chem. Abstr. 105, 90145q
19) Teo, S.B.; Tech, S.G. Inorg. Chem. Acta 1985, 107, 35; Chem. Abstr. 103, 63855y 20) Koola, J.D.; Brintzinger, H.H. J. Chem. Soc., Chem. Commun. 1976, 388; Chem. Abstr. 85, 124088j 21) Nesmeyanov, A.N.; Chapovskii, Y.A.; Ustynyuk, Y.A. Izv. Akad. Nauk SSSR, Ser. Khim. 1966, 1871; Chem. Abstr. 66, 64860a 22) Chao, T.; Epsenson. J.H. J. Am. Chem. Soc. 1987, 100, 129; Chem. Abstr. 88, 111148r 23) Saito, T.; Munakata, H.; Imoto, H. Inorg. Synth. 1977, 17, 83; Chem. Abstr. 88, 121313e 24) Takagi, K. Chem. Lett. 1986, 265; Chem. Abstr. 105, 208796h 25) Meakin, P.; Guggenberg, L.J.; Peet. W.G.; Muetterties, E.L.; Jesson, J.P. J. Am. Chem.Soc. 1973, 95, 1467; Chem. Abstr. 78, 101033c 26) Corey, E.J.; Suggs, J.W. J. Org. Chem. 1975, 40, 2554; Chem. Abstr. 83, 130658v 27) Birnbaum, E.R.; Javora, P.H. J. Organomet. Chem. 1967, 9, 379; Chem. Abstr. 68, 22026u 28) Young, R.; Wilkinson, G. Inorg. Synth. 1977, 17, 75; Chem. Abstr. 88, 105484f
*For Online Consulting Only
157
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
29) Empsail, H.D.; Hyde, E.M.; Pawson, D.; Shaw, B.L. J. Chem. Soc., Dalton Trans 1977, 1292; Chem. Abstr. 87, 168176g 30) Eur. Pat. Appl. 55, 487 1982; Chem. Abstr. 98, 4675v 31) Bell, B.; Chatt, J.; Lkeigh, G.J. J. Chem. Soc., Dalton Trans. 1973, 997; Chem. Abstr. 78, 154371u 32) Werner, H.; Zenkert, K. J. Chem. Soc., Chem. Commun. 1985, 1607; Chem. Abstr. 105, 97654p 33) Moulton, C.J.; Shaw, B.L. J. Chem. Soc., Chem. Commun. 1976, 365; Chem. Abstr. 85, 136363h 34) Meyer, W.R.: Venanzi, L.M. Angew, Chem. 1984, 96, 505; Chem. Abstr. 101, 64917r 35) Greene, T.R.; Roper, W.R. J. Organomet. Chem. 1986, 299, 245; Chem. Abstr. 105, 226938k 36) Hambrick, G.A.; Froelich, P.N.; Andreae, M.O.; Lewis, B.L. Anal. Chem. 1984, 56, 421; Chem. Abstr. 100, 90972d 37) Hattori, Y.; Kobayashi, A. et. al. J. Chromatogr. 1984, 315; 341; Chem. Abstr. 102, 100497k 38) D’Uliva, A.; Fouco, R.; Papoff, P. Talanta 1986, 33, 401; Chem. Abstr. 105, 90513h
39) Brunner, H.; Watchter, J. J. Organomet. Chem. 1980, 201, 453; Chem. Abstr. 94, 102685k 40) Brookhart, M.; Lukacs, A. J. Am. Chem. Soc. 1984, 106, 4161; Chem. Abstr. 101, 91137t 41) Sullivan, B.P.; Meyer, T.J. J. Chem. Soc., Chem. Commun. 1984, 1244; Chem. Abstr. 102, 55034u 42) Davies, D.L.; Knox, S.A.R. et. al. J. Chem. Soc., Dalton Trans. 1984, 2293; Chem. Abstr. 102, 113688y 43) Jacobsen, E.N.; Bergman, R.G. J. Am. Chem. Soc. 1985, 107, 2023; Chem. Abstr. 102, 149512a 44) Catheline, D.; Lapinte, C.; Astruc, D.C. R. Acad. Sci., Ser 2 1985, 301, 479; Chem. Abstr. 104, 186591n 45) Latov, V.K.; Belikov, V.M.; Belyaeva, T.A.; Vinogradova, A.I.; Soinov, S.I. Izv. Akad. Nauk SSR, Ser. Khim. 1977, 2481; Chem. Abstr. 88, 104852n 46) Holy, N.L. Tetrahedron Lett. 1977, 3703; Chem. Abstr. 88, 104735b 47) U.S. 4,062,803 1977 Corresponds to Ger. Offen. 2,600,634 1976; Chem. Abstr. 85, 198875k 48) U.S. 4,313,018 1982; Chem. Abstr. 96, 141870c 49) Kaesz. H.D. Chem. Brit. 1973, 9, 344; Chem. Abstr. 79, 86879j 50) U.S. 3,676, 523 1972; Chem. Abstr. 77, 100710q
*For Online Consulting Only
158
Rohm and Haas : the Sodium Borohydride Digest
51) 52) 53) 54)
U.S. 3,686, 351 1972; Chem. Abstr. 77, 151422e U.S. 3,737, 475 1973; Chem. Abstr. 79, 31448n U.S. 3,825,615 1974; Chem. Abstr. 81, 119895h Keyes, W.E.; Legg, J.I. J. Am. Chem. Soc. 1976, 98, 4970; Chem. Abstr. 85, 108969s 55) King, R.B.; Frazier, C.C.; Hanes, R.M.; King, A.D. J. Am. Chem. Soc. 1978, 100 2925; Chem. Abstr. 88, 198376k 56) Jpn. Kokai Tokkyo Koho 84, 115,752 1984; Chem. Abstr. 101, 213057q
*For Online Consulting Only
press -F for Searching
159
160
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
C. NaBH4 Derivatives
via rapid and reversible protonation of the β-carbon generating a readily reducible imminium salt:
NaBH3CN Alembic 1, 3, 7, 8, 15, 18, 23, 44, 46 Sodium cyanoborohydride, which is soluble in a wide variety of solvents and is hydrolytically stable to a pH of approximately 3, has extremely interesting properties (1-4). Under neutral conditions in water and methanol, the reduction of aldehydes and ketones is insignificant; however, at pH 3-4, rapid reduction to the alcohol occurs (5,6). The imine group, >C=N-, is reduced by cyanoborohydride much more rapidly than carbonyls, providing a convenient and efficient route to the reductive amination of aldehydes and ketones (5,7-10). RR’C=O + R”NH2 + NaBH3CNÆ RR’CHNHR” The reaction is general for ammonia, primary and secondary amines, all aldehydes and unhindered ketones. Smooth reductions of acid chlorides and enamines are also possible with NaBH3CN, the latter
*For Online Consulting Only
N H
H+
BH3CN-
N+
H
H
N H
H
H
The versatility of this reagent is further demonstrated in a number of selective reductions of a variety of organic functional groups, for example, in the selective reduction of aldehydes and ketones to hydrocarbons via their tosy hydrazones (11-14), selective reduction of alkyl bromides, iodides and tosylates to hydrocarbon (15,16), reductive alkylation of amines and hydrazines (17,18) and of amides (19). NaBH3CN has also been applied in some interesting synthetic reactions, e.g. synthesis of N-labeled alkaloids (20), and amino acids (5), reduction of pyridines exclusively to the 1,4 dihydro derivatives (21), and synthesis of epoxy-Nnitrocarbamates (22). An excellent review article on the utility and applications of cyanoborohydride has been published (23).
Rohm and Haas : the Sodium Borohydride Digest
Polymer bound borohydride reducing reagents (borohydride exchange resins) Alembic 13, 52
100 BER in MeOH
80 60
Polymeric-bound borohydride (24,25), PNR3+BH4-, (borohydride exchange resins) offer several advantages over sodium borohydride. The primary advantage are the convenience of use of these materials and the minimal introduction of ionic species or organic by products into the treated bulk media. The reactivity of these borohydride exchange resins depends on the skeletal structure/pore size of the resins, the nature of the solvents, the nature of the reducing reagent and the type of co reagent used.(26) Fig. 12 Stability of Borohydride Exchange Resins in Alcohols
*For Online Consulting Only
161
press -F for Searching
NaBH4 in MeoH
40 BER in 95%Et OH
20 0 0
50
100
NaBH4 in 95%Et OH
Ti m e M i nu t e s
Borohydride exchange resins have been shown to be an effective reducing agents for the reduction of many functional groups such as aldehyde and ketones (27-34), azides (35,36), reductive amination (37-39), synthesis of thioethers (40-43), thiols (44) and disulfides (45,46), hydroboration of alkenes (47,49) and alkynes (50,51), dehalogenantion (52-55), carboxylic acids (56-57), nitro (58), anhydrides (59), hydrazones (60), cyanides (61), oximes (62), deoxygenantion of amine N-oxides (63-65) and the coupling of alkenes and halides (66-69). Chiral reductions of ketones have been achieved using chiral polymers as support. (70-71) The combination of sodium borohydride and ion exchange resins stabilize the borohydride towards solvolysis with protic solvents such as methanol and ethanol. The graphs
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
which follows demonstrate the stability that can be achieved by combing ion exchange resins with sodium borohydride. Other applications in which borohydride exchange resins have been used for are; purification of solvents, generation of volatile hydrides and reduction of metal ions. The anion exchange resins are generally of the styrene/divinylbenzene gel and macroreticular types such as Amberlitetm 400, although the triethylmethyl ammonium cellulose anion exchange has been reported (72-73) Anion exchange resin supported cyanoborohydride (styrene/divinylbenzene macroreticular type) has been utilized in a variety of reductions previously developed for the sodium salt (23). While the reductions are slower with resin, selectivity is retained.
alkenes, alkynes, imines, nitro, esters, and reductive amination of aldehydes and ketones in high yields and under mild reaction conditions in polar solvents such as tetrahydrofuran.. (74-83) This technique has been extended to other solid supports such as alumina (84-86), zeolites (87) and alumino phosphates (88,89).
Other Solid Supports for Borohydrides It has been demonstrated that silica gel impregnated with NaBH4 or Zn(BH4)2 can selectively reduce ketones and aldehydes in nonpolars such as hexane, and other functional groups such as epoxides,
*For Online Consulting Only
Alembic: 4
NaBH2S3 (Lalancette’s Reagent)
When sodium borohydride and sulfur are allowed to react at room temperature in THF (90) there is a rapid evolution of hydrogen, and sulfurated sodium borohydride NaBH2S3 is formed: 8 NaBH4 + 3 S8 Æ 8 NaBH2S3 + 8 H2. This reagent reduces aldehydes to the alcohols at low temperatures (91,92) and form sulfides and thiols at about 60o C (93). The reagent has also been used to prepared thioacetals in quantitative yields (94). The reduction of ketones (95,96), oximes (97-99), epoxides (100) and episulfides (101) has also been reported. NaBH2S3 is intermediate in reducing potential between LiAlH4 and NaBH4 and reductions of functional groups containing nitrogen are particularly facile (97-105). Aromatic nitro
162
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
compounds are reduced to amines selectively; halogen, ether olefin nitriles, ester, acid groups are inert to the sulfurated borohydride. Primary aliphatic nitro groups are converted to the nitrile and secondary to a mixture of ketones and the corresponding oxime, amides and nitroso compounds are reduced to amines, as are aromatic nitriles when the reducing agent is present in excess. When excess nitrile is present, the corresponding thioamide is formed.
A number of trialkoxy derivatives have been reported, including R= Me, Et, CH(CH3)2, CHEtMe (110-112) and CH2CH2OCH3 (2-methoxyethoxy) (113). Trialkoxyhydridoborates reduce aldehydes, ketones, acid chlorides, and acid anhydrides. At low temperatures acid chlorides are reduced to aldehydes. Ester and nitriles are slowly reduced at elevated temperatures. The bulky secbutoxy derivatives, NaBH(OCHEtMe)3, have been used in the stereoselective reduction of steroidal ketones (114). Reductive amination of aldehydes and ketones with amines have been demonstrated in high yields using alkoxy borohydrides. Many examples of nitrogen – carbon double bonds have been reduced to amines in high yields using this reagent. Bis and tris aryl methanol can be reduced to alkanes using trialkoxy borohydrides.
NaBH(OR)3, Sodium Hydridotrialkoxyborates Alembic: 14, 25, 31, 33 Over the years many papers relating to the reduction of many functional groups such as indoles, imines, enamines, oximes, amides, nitriles, alcohols to hydrocarbon, ketones to hydrocarbon, acetals, ketals, ethers, aldehydes, ketones, and alkenes or reductive amination of ketones and aldehydes have been published. Summaries of these works have been published in a few informative reviews. (106-109) Examples of these reactions are shown below.
*For Online Consulting Only
NaBH4 Polyamine polymers By chelating the sodium ion with polyamine, PMDT (N,N,N’,N’,N’-pentamethyldiethylenetriamine), CH3N[CH2CH2NCH3)2]2, NaBH4 becomes solubulized in hydrocarbon solvents (115). Many reductions can be carried out in non-polar solvents.(116)
163
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
The multi amine containing organic molecules, DABCO (117,118) and polyvinyl pyridine (119,120), polypyrazine (121, 122) can complex to sodium and zinc borohydride to form very efficient reducing reagents.
group. A major use of potassium borohydride is in the synthesis of lithium borohydride. Potassium borohydride is synthesized by the reaction of sodium borohydride with potassium hydroxide in water. The potassium borohydride drops out of solution and is isolated as a white solid in high yield and purity. (126-127)
Lithium Borohydride (LiBH4) Alembic 52 Lithium borohydride (LBH) is a stronger reducing agent then either potassium or sodium borohydrides. LBH will reduce aldehydes, ketones, acid chlorides, esters, epoxides, lactones and nitriles. It can be formed in situ by reacting either sodium or potassium borohydride with lithium chloride in an ether solvent or liquid ammonia. (123-125) Potassium Borohydride (KBH4) Alembic 53 Potassium borohydride (KBH) has the same solubility and reductive power as sodium borohydride. KBH will reduce aldehydes, ketones, acid chlorides and epoxides, and lactones that contain α-withdrawing
*For Online Consulting Only
Calcium Borohydride (Ca(BH4)2) Calcium borohydride (CaBH) has similar solubility and reductive power as lithium borohydride. CaBH will reduce aldehydes, ketones, acid chlorides, esters and epoxide. Calcium borohydrides is used to synthesize lactones from hemiesters and to stereoselectively reduce ketones by forming a sterically hindering metal complex. CaBH is synthesized by combining CaCl2 and sodium borohydride in either THF or methanol. Solid Ca(BH4)2•6THF is isolated when THF is used as the reaction solvent. (128, 129) Zinc Borohydride (Zn(BH4)2 Alembic 48, 58 Zinc borohydride is a strong reducing agent that will reduce aldehydes, ketones, acid chlorides, esters, epoxide, azides, α,β ethylenic ketones to allylic alcohols, and
164
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
carboxylic acids. Zinc borohydride can selectively reduce aldehydes in the presence of ketones and aliphatic ketones in the presence of aromatic ketones. Reviews on the use of this reagent have been published. (130,131) This reagent has been combined with solid supports such as silica gel and ion exchange resins to make a more robust reducing reagent.(132137) Polypyrazine and DABCO have been combined with zinc borohydride to form a polymeric solid reducing reagent. Zinc borohydride can exist as a dimeric compound when synthesized from LBH and ZnCl2 in diethyl ether. A more complex solution of zinc borohydrides are formed when prepared from SBH and ZnCl2 in THF or DME. In most cases this reagent is formed in situ and used as a freshly made before each use. (138-144)
Esters and Acids The system using NaBH4 and AlCl3 in dyglme, reported by brown and co-workers (145,146) gives good yields in the reduction of saturated acids and esters to alcohol at Room temperature. Unsaturated esters, diesters and diacids are also reduced, but the reaction is complicated by formation of difficulty hydrolyzed boron complexes. LiCl and NaBH4 in THF (147-149) also reduce esters readily to alcohols; LiBH4 is formed and consumed in situ. NaBH4 and CaCl2 in ethanol also effectively reduce esters (150-15). Enhanced reduction efficiency of NaBH4 has been reported in the presence of TiCl4 (153). Not only are esters reduced, but also many other functional groups causing problems with NaBH4 and AlCl3 are smoothly reduced using a 4 to 1 molar ratio of NaBH4 to TiCl4 in diglyme. This system reduces diesters and anhydrides to diols.
Mixed Hydrides Several systems have been devised, adding to the number of functional groups that can be reduced effectively with NaBH4. In these, the reducing power of NaBH4 is enhanced to differing degrees.
*For Online Consulting Only
Acetals and ketals NaBH4 in combination with either AlCl3 or BF3 in diglyme reduces acetals and ketals to their corresponding ether (154).
165
Rohm and Haas : the Sodium Borohydride Digest
Hydroboration Alembic 60 Diborane, prepared from NaBH4 and I2, BF3, Me3SlCl, TiCl4 or H2SO4 reacts rapidly and quantitatively in ether solvents with organic unsaturation to form organoboranes (155,156), >B-H + CH2=CHR Æ B-CH2CH2R which can serve as reactive intermediates in organic synthesis. This methodology is also capable of reducing the following functional groups: nitrile (157,158), epoxides (159,160), carboxylic acids (161171), amides (172-176), esters (177), oximes (178), nitro (179,180), olefinic bonds (181, 182) as well as reductive amination of ketones and aldehydes (183186). Stereoconfiguration is retained and, in contrast with Grignard reagents, the reagent is compatible with most functional groups. The intermediates organoboranes undergo a wide variety of reactions, as shown in Table VI, including isomerization (187,188), displacement (189,
*For Online Consulting Only
press -F for Searching
190), cyclization (188, 191), protonolysis to hydrocarbons (192), oxidation to alcohols (193), ketones (194 ), and carboxylic acids (195) (depending on the reagents used), amination (196, 197), metallation (198), coupling (199, 200) and 1, 2, 3 and 4 carbon homoolgations, alkylation and arylation (201) and conjugated addition (202). Carbonlyation of organoboranes at low pressures provides a route to primary, secondary and tertiary alcohols (203-205), aldehyde (206) and ketones, methanol derivatives and polycyclics (207).
166
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest
Table VI Organoborane Reactions Reaction Amination Coupling Cyclization
Reactants C-B 2 (C-B) C-C H-B
Means H2NOSO3H Alk. AgNO3 heat
Prodcdut C-NH2 C-C C-B
Displacment Homologation 1C 2C
R-C-C-B
R’CH=CH2
RCH=CH2
C-B
3C
CO α-haloester (+ KOtBu) CH2=CHCHO
4C
CH2=CHC(O)CH3
C-C-B CCH2CO2R CCH2CH2CHO CCH2CH2C(O)CH3 C-C-C-B
Isomerization Metalation Oxidation To alcohols To Ketones To Acids Protonation
C-C-C B C-B
heat Alk. M salt Alk. H2O2 H2CrO4 1. H2CrO4 2. RCOOOH RCOOH + heat
*For Online Consulting Only
C-M C-OH C=O C-CO2H C-H
Other Derivatives The reducing power of sodium borohydride can further be enhanced in the presence of a reagent such as carboxylic acid, thiol compounds or anilide. Such systems are becoming more important and have greatly extended the scope of this reagent. The active species in these systems have not been isolated and the reducing agent are prepared and used insitu. Table VII summarizes the results.
167
Table VII Alkoxyborohydrides Reagent (mole ratio) NaBH4/ CH3CO2H (1:3.25)
Proposed intermediate STAB
NaBH4./ CH3CO2H (1:1) NaBH4/ CH3CO2H (excess)
SMAB
NaBH4/ CH3CO2H (6.5:1) NaBH4/ RCO2H (excess) NaBH4./ CF3CO2H (excess)
STAB
STRB STFAB
*For Online Consulting Only
168
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest
Reduction
ref
Reduction of aldehydes Reductive alkylation of quinoline and isoquinoline Reduction of amides and amines N-alkylation of aromatic amines and indoles Reductive deoxygenantion of carbonyl tosyl hydrazones Reduction of nitrimines to nitramines Reductive alkylation of oximes Reduction of carbonols and ketones to alkanes
208 209
210 211 212 213
214 216 215
NaBH4 /CF3CO2H (1:1) NaBH4/phthalic acid (1:1) NaBH4/thiol
SMFAB NaH2B (phthalato)
NaBH4/anilide (1:1)
NaH3B anilido)
NaBH4/ NaOH)
NaH3BOH
STAB= NaBH(O2CCH3)3 SMAB= NaBH3(O2CCH3) STRB= NaBH(O2CR)3 STFAB=NaBH(O2CCF3)3 SMFAB=NaBH3(O2CCF3)
Reduction of nitriles to amines Reduction of nitriles to amines Reduction of nitro compounds, esters, amides and imide Reduction of esters, aldehydes and ketones, acid chlorides Reduction of esters, nitriles and nitro compounds
217 218 219 220 221 222223224
225226
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
References: 1) Wade, R.C.; Sullivan, E.A.; Berschied, Jr, J.R.; Purccell, K.F. Inorg. Chem. 1970, 9, 2146; Chem. 73, 83350 2) Kreevoy, M.M.; Hutchins, J.E.C. J. Am. Chem. Soc. 1969, 91, 4329; Chem. Abstr. 71, 54148p 3) Berschied, Jr. J.R.; Purcell, K.F. Inorg. Chem. 1970, 9, 624; Chem. Abstr. 72, 96136j 4) Levine, L.A.; Kreevoy, M.M. J. Am. Chem. Soc. 1972, 94, 3346; Chem. Abstr. 77, 10408t 5) Borch, R.F.; Bernstein, M.D.; Durst, H.D. J. Am. Chem. Soc. 1971, 93, 2897; Chem. Abstr. 75, 49525n 6) Pfeil, J.L.; Kukolja, S.; Paquette, L.A. J. Org. Chem. 1981, 46, 827; Chem. Abstr. 94, 139711s 7) Rosen, G.M.; J. Med. Chem. 1974, 17, 358; Chem. Abstr. 81, 33187 8) Inokoshi, J.; Nakagawa, A.; Tanaka, H. Omura, S. J. Antibiot 1983, 36, 1713; Chem. Abstr. 100, 97722e 9) Mathis, C.A.; Shulgin, A.T.; Sargent, T. J. Labelled Cmpd. Radiopharm. 1986, 23, 115; Chem. Abstr. 105, 225903
10) U.S.4,593,118 1986; Chem. Abstr. 105, 97020d 11) Hutchins, R.O.; Marynoff, B.E.; Milewski, C.A. J. Am. Chem. Soc. 1971, 93, 1793; Chem. Abstr. 77, 113763j 12) Hutchins,R.O.; Karcher, M.; Rau, J. Org. Chem. 1975, 40, 923; Chem. Abstr. 85, 122714m 13) Mahajan, J.R.; de Araujo, H.C. Synthesis 1981, 49; Chem. Abstr. 94, 204868d 14) Avasthi, K.; Salomon, R.G. J. Org. Chem. 1986, 51, 2556; Chem. Abstr. 105, 23981w 15) Hutchins, R.O.; Kandasamy, D.; Marynoff, C.A.; Masiamani, D.; Marynoff, B.E. J. Org. Chem. 1977, 42, 82; Chem. Abstr. 86, 54918z 16) Mazzocchi, P.; Ammon, H.L. et. al. J. Org. Chem. 1981, 46, 4530; Chem. Abstr. 95, 187016m 17) Borch, R.F.; Hassid, A.I. J. Org. Chem. 1972, 37, 1673; Chem. Abstr. 77, 19272b 18) Gidley, M.J.; Sanders, J.K.M. Biochem. J. 1982, 203, 331; Chem. Abstr. 97, 35620g 19) Basha, A.; Orlando, J.; Winreb, S.M. Synth. Commun. 1977, 7, 549; Chem. Abstr. 88, 136117t 20) Leete, E.; Isaacson, H.V.; Durst, H.D. J. Label. Compounds 1971, 7, 313; Chem. Abstr. 76, 14762f
*For Online Consulting Only
169
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
21) Eiser, U.; Kuthan, J. Chem. Rev. 1972, 72, 1; Chem. Abstr. 76, 723221x 22) Pdwa, A.; Cimiluca, P.; Eastman, D. J. Org. Chem. 1972, 37, 805; Chem. Abstr. 76, 126164u 23) Hutchins, R.O.; Natale, N.R. Org. Prep. Proced. Int. 1979, 11, 201; Chem. Abstr. 92, 40740x 24) U.S. 4,107,099 1978; Chem. Abstr. 90, 55971f 25) Gibson, H.W.; Baily, F.C. J. Chem. Soc., Chem. Commun. 1977, 815; Chem. Abstr. 88, 152171m 26) Sande, A.R.; Jagadale, M.J. Tetrahedron Lett. 1984, 3501 27) Yoon, N.M.; Gyong, Y.S. Bull Korean Chem. Soc. 1987, 8, 162 28) Yoon, N.M.; Park, K.B. Gyoung, Y.S. Tetrahedron Lett. 1983, 5367 29) Bangar, B.P.; Kshinsagar, S.N. Wadgaonkar, P.P. Synth. Commun. 1995, 25, 941 30) Ahindra, N.; Ashio, S. Synth. Commun. 1987, 1007 31) Caycho, J.R.; Tellado, F.G.; Armas, P.D.; Tllado, J.J.M. Tetrahedron Lett. 1997, 38, 277 32) Tamami, B.; Gourdarzian, N. J. Chem. Soc. , Chem. Commun. 1994, 1079
33) Gyoung, Y.S.; Yoon, N.M.; Joen, D.H. Bull. Korean Chem. Soc. 1987, 8, 162 34) Yoon, N.M.; Choi, J. Shon, Y.S. Synth. Commun. 1993, 23, 3047 35) Kalbalka, G.W.; Wadgaonkar, P.P.; Chatla, N. Syn. Commun. 1990, 20, 293 36) Yoon, N.M.; Kim, E.G.; Son, H.S.; Choi, J. Synth. Commun. 1990, 23, 1595 37) Lee, S.Y.; Cho, B.T.; Yoon, N.M. Bull. Korean Chem. Soc. 1998, 19, 1268 38) Nah, J.H.; Kim, S.Y.; Yoon, N.M. Bull. Korean Chem. Soc. 1998, 19, 269 39) Yoon, N.M.; Choi, J.; Ahn, J.H. J. Org. Chem. 1994, 59, 3490 40) Nah, J.H.; Choi, J.; Yoon, N.M. Bull. Korean Chem. Soc. 1996, 17, 73 41) Choi, J.; Lee, D.W.; Yoon, N.M. Bull. Korean Chem. Soc. 1995, 16, 189 42) Lee, D.W.; Choi, J. Yoon, N.M. Synth. Commun. 1996, 2189 43) Choi, J.; Yoon, N.M. Synth. Commun. 1995, 2655 44) Choi, J; Yoon,N.M. JJ. J. Org. Chem. 1995, 60, 3266 45) Choi, J.; Yoon, N.M. Synlett 1995, 1073
*For Online Consulting Only
170
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
46) Chen, J.W.; Qin, C.Q. Chinese Chem. Letter. 1991, 2, 125 47) Choi, J.; Yoon, N.M. Synthesis, 1996, 596 48) Yoon, N.M.; Sim, T.B. Bull. Korean Chem. Soc. 1993, 14, 749 49) Choi, J. Yoon, N.M. Tetrahedron Lett. 1996, 37, 1057 50) Yoon, N.M.; Park, K.B.; Lee, H.J.; Choi, J. Tetrahedron Lett. 1996, 37, 8527 51) Yoon, M.N.; Lee, H.J. Ahn, J.H.; Choi, J. J. Org. Chem. 1994, 59, 4687 52) Yoon, M.N.; Choi, J.; Lee, H.J. Bull. Korean Chem. Soc. 1993, 14, 543 53) Krishnamurthy, S.; Brown, H.C. J. Org. Chem. 1982, 47, 276 54) Krishnamurthy, S.; Brown, H.C. J. Org. Chem. 1983, 48, 3085 55) Anand, R.C.; Vimal Tetrahedron Lett. 1998, 39, 917 56) Joshi, D.D.; Sagar, A.D.; Hilage, N.P.; Salunkhe, M.M. Indian J. Chem. 1993, 32b, 1201 57) Yoon, N.M.; Choi, J. Synlett 1993, 135
58) Bandgr, B.P.; Modhave, R.K.; Wadgaonkar, P.P.; Sande, A.R. J. Chem. Soc. Perkin Trans 1 1996, 1993 59) Kim, S.Y.; Yoon, N.M. Bull. Korean Chem. Soc. 1998, 19, 891 60) Yoon, N.M.; Choi, J. Synlett 1993, 135 61) Bandagar, B.P.; Nikat, S.M. Synth. Commun. 1995, 25, 863 62) Yoon, N.M.; Pure and Appl. Chem. 1996, 68, 843 63) Bangar, B.P.; Kshinsagar, S.N. Wadgaonkar, P.P. Synth. Commun. 1995, 25, 863 64) Sim, T.B.; Ahn, J.H. Yoon, N.M. Synthesis, 1996, 324 65) Sim, T.B.; Choi, N.M. Tetrahedron Lett. 1996, 37, 3137 66) Cekovic, Z.; Saicic, R. Tetrahedron Lett. 1986, 27, 5893 67) Ahn, J.H.; Lee, D.W.; Joung, M.J.; Lee, K.H.; Yoon, N.M. Synlett. 1996, 1224 68) Joung, M.J.; Ahn, J.H.; Lee, D.W.; Yoon, N.M. J. Org. Chem. 1998, 63, 2755 69) Adjidjonou, K.; Caze, C. Eur. Poly. J. 1994, 30, 395 70) Adjidjonou, K.; Caze, C. Eur. Poly. J. 1995, 31, 749 71) Cook, M.M.; Wagner, S.E. Mikulki, R.A.; Demko, D.P.; Clements, J.G. ACS Symp. Ser. #187, 1980, 195; Chem. Abstr. 94, 65044c
*For Online Consulting Only
171
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
72) Perrier, D.M.; Denerito, R.R. Appl. Polym. Symp. No 29, 1976, 213; Chem. Abstr. 85, 65052t 72) U.S. 4,032,292 1977; Chem. Abstr. 87, 54485b 73) Ranu, B.C.; Das, A.R. J. Chem. Soc. Perkin Trans. 1 1992, 1881 74) Ranu, B.C.; Das, A.R. J. Chem. Soc. Chem. Commun. 1990, 1334 75) Ranu, B.C.; Chakraborty, R.; Saha, M. Tetrahedron Lett. 1993, 34, 4659 76) Ranu, B.C.; Sarkar, A.; Saha, M.; Charkraborty, R. Tetrahedron 1994, 50, 6579 77) Ranu, B.C.; Das, A.R. J. Org. Chem. 1991, 56, 4796 78) Ranu, B.C.; Majee, A. Sarkar, A. J. Org. Chem. 1998, 63, 370 79) Yakabe, S.; Hirano, M.; Morimoto, T. Synth. Commun. 1999, 29, 295 80) Ranu, B.C.; Sarkar, A.; Majee, A. J. Org. Chem. 1997, 62, 1841 81) Ranu, B.C.; Basu, M.K. Tetrahedron Lett. 1991, 32, 3243 82) Ranu, B.C.; Charkraborty, R. Tetrahedron, 1992, 48, 5317
83) Yakabe, S.; Hirano, M.; Morimoto, T. Can J. Chem.. 1998, 76, 1916 84) Yakabe, S.; Hirno, M.; Clark, J.H.; Morimoto, T. J. Chem. Research (S) 1998, 322 85) Varma, R.S.; Saini, R.K. Tetrahedron Lett. 1997, 38, 4337 86) Sreekumar, R.; Padmakumar, R.; Rugmini, P. Tetrahedron Lett. 1998, 5151 87) Campelo, J.M.; Chakraborty, R.; Marinas, J.M. Synth. Commun. 1996, 26, 415 88) Campelo, J.M.; Chakraborty, R.; Marinas, J.M. Synth. Commun. 1996, 26, 1639 90) Lalancette, J.M.; Freche, A.; Monteux, R. Can. J. Chem. 1968, 46, 2754; Chem. Abstr. 69, 83101g 91) Lalancette, J.M.; Freche,A; Brindle, J.R.; Laiberte, M. Synthesis 1972, 526; Chem. Abstr. 78, 4403s 92) Lalancette, J.M.; Freche, A. Can. J. Chem. 47, 739; Chem. Abstr. 70, 77506x 93) Brindle, J.R. Liard, J.L. Can. J. Chem. 1975, 53, 1480; Chem. Abstr. 83, 163753a 94) Lalancette, J.M.; Lachance, A. Can. J. Chem. 1969, 47, 859; Chem. Abstr. 70, 77245m 95) Lalancette, J.M.; Freche, A. Can. J. Chem. 1970, 48, 2366; Chem. Abstr. 73, 76616h
*For Online Consulting Only
172
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
96) Ramanujam, V.M.S.; Ffieff, N.M. J. Chem. Soc., Perkin 2 1976, 1811; Chem. Abstr.. b86, 154933u 97) Lalancette, J.M.; Brindle, J.R. Can. J. Chem. 1970, 48, 2366; Chem. Abstr. 72, 110402b 98) Jpn. Kokai Tokkyo Koho 81, 122,386 1981; Chem. Abstr. 96, 122832a 99) Yamaguchgi, I. Kenkyu Kio-Tokyo Kasei Daigaku 1984, 24, 155; Chem. Abstr. 103, 104662d 100) Lalancette, J.M.; Freche, A. Can. J. Chem. 1971, 49, 4047; Chem. Abstr. 76, 85121g 101) Lalancette, J.M. Freche, A Tetrahedron Lett. 1973, 47, 1404; Chem. Abstr. 79, 52911y 102) Lalancette, J.M. Freche, A Tetrahedron Lett. 1971, 49, 1990; Chem. Abstr. 75, 151488q 103) Brindle, J.R.; Liard, J.L.; Berube, N. Tetrahedron Lett 1976, 54, 871; Chem. Abstr. 85, 123471s 104) Miller, R.B.; Frincke, J.M. J. Org. Chem. 1980, 45, 5312; Chem. Abstr. 94, 47103s 105) Jpn. Kokai Tokkyo Koho 85, 152,497 1985; Chem. Abstr. 104, 69119d
106) Gribble, G.W.; Nutatitis, C.F. Org. Prep Proc. Int. 1985, 17, 317 107) Gribble, G.W. Reduction in Organic Synthesis, ACS Symposium Series, 1996, 641, 167 108) Gribble, G.W. Chemtech 1996, 12, 26 109) Gribble, G.W. Chemical Society Reviews 1998, 27, 395 110) Brown, H.C. Mead, E.J. J. Am. Chem. Soc. 1953, 75, 6263; Chem. Abstr. 5705e 111) Brown, H.C. Mead, E.J.; Shoaf, C.F. J. Am. Chem. Soc. 1953, 75, 6263; Chem. Abstr. 51, 3435g 112) Brown, H.C.; Cha, J.S.; Nazer, B. Inorg.Chem. 1984, 23, 2929; Chem. Abstr. 100, 121881a 113) Kriz, O.; Stucklik, J.; Socochor, P.; Stronf, O. Collect. Czech. Chem. Commun. 1977, 42, 421; Chem. Abstr. 86, 188544h 114) U.S. 3,853,927 1974; Chem. Abstr. 82, 86499x 115) Ger. Offen. 2,137, 273 1972; Chem. Abstr. 77, 22412c 116) Private communication. W.R. Moser, Badger Company, Inc., Waltham, Mass. 117) Firouzabadi, H.; Adibi, M.; Zeynizadeh, B. Synth. Commun. 1998, 28, 1257 118) Tamami, B.; Goudarzian, N. J. Chem. Soc., Chem. Commun. 1994, 1079
*For Online Consulting Only
173
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
119) Tamami, B.; Lakouraj, M.M. Synth. Commun. 1995, 25, 3089 120) Kuznetsov, N.T.; Moltseva, N.N.; Kedrova, N.S.; Saidov, B.I.; Chumaevskii, N.A. Koord. Khim. 1992, 18, 456 121) H.C.; Choi, Y.M.; Narasimhan, S. Inorg. Chem. 1982, 21,3657 122) JP 04224585 1992 123) EP 0072897 1983 124) U.S. 2,741,539 1956 125) U.S. 2,741,540 1956 126) Brown, E.; Robin, J.P.; Dhal, R. Tetrahedron 1982, 38, 2569 127) Brown, E.; Robin, J.P.; Dhal, R. Tetrahedron 1989, 45, 141 128) Narasimhan, S.; Balakumar, R. Aldrichimica Acta, 1998, 31, 19 129) Ranu, B.C. Synlett 1993, 885 130) Ranu, B.C.; Majee, A.; Sarkar, A. J. Org. Chem. 1998, 63, 370 131) Ranu, B.C.; Sarkar, A.; Saha, M.; Chakraborty, R. Tetrahedron 1994, 6579
132) Sreekumar, R.; Padmakumar, R.; Rugmini, P. Tetrahedron Lett. 1998, 5151 133) Campelo, J.M.; Chakroborty, R.; Marinas, J.M. Synth. Commun. 1996, 26, 1639 134) Campelo, J.M.; Chakroborty, R.; Marinas, J.M. Synth. Commun. 1996, 26, 412 135) Tamami, B.; Goudarzian, N.; Kiasat, A.R. Eur. Polym. J. 1997, 33, 977 136) Brown, H.C.; Krishnamurthy, S. Tetrahedron 1979, 25, 567 137) Kim, S.; Hong, C.Y.; Yang, C. Angew. Chem. Int. Ed. Engl. 1983, 22, 562 138) Oishi, T.; Nakata, T. Acc. Chem. Res. 1984, 17, 338 139) Ranu, B.C. Synlett 1993, 885 140) Walker, E.R.H. Chem. Soc. Rev. 1976, 35, 449 141) Salunkhe, A.K.; Brown, H.C. Tetrahedron Lett. 1995, 36, 7989 142) Crabbe, P.; Garcia, G.A.; Rius, C. J. Chem. Soc., Perkin Trans. 1 1973, 810 143) Brown, H.C.; Subba Rao, B.C. J. Am. Chem. Soc. 1955, 77, 3164; Chem. Abstr. 50, 3995c 144) Brown, H.C.; Subba Rao, B.C. J. Am. Chem. Soc. 1956, 78, 2582; Chem. Abstr. 51, 1077c
*For Online Consulting Only
174
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
145) Paul, R.; Joseph, N. Bull. Soc. Chim. France 1952, 550; Chem. Abstr. 47, 3265I 146) Heeres, J.; Backx, L.J.J.; Van Cutsem, J. J. Med. Chem. 1977, 20, 1516; Chem. Abstr. 87, 167942s 147) U.S. 4,512,991 1985; Chem. Abstr. 103, 71338x 148) Banerji, J.; Das, B. Heterocycels 1985, 23, 661; Chem. Abstr. 102, 220614t 149) Takata, T.; Kuo, M. et. al. Chem. Lett. 1985, 939; Chem. Abstr. 104, 5808v 150) Jpn Kokai Tokkyo Koho 875, 178, 845 1985; Chem. Abstr. 104, 8816s 151) Subba Roa, B.C.; Current Sci. 1961, 30, 218; Chem. Abstr. 56, 3326c 152) Subba Rao, B.C.; Janaki, N.; Pathak, K.D. Indian J. Chem. 1965, 3, 123; Chem. Abstr. 63, 5548g 153) Brown, H.C. “ Hydroboration:” W.A. Benjamin, Inc. New York, N.Y. 1962 154) Brown, H.C. “ Organic Synthesis via Boranes”, John Wiley and sons, New York, N.Y. 1975 155) Urabe, H.; Aoyama, Y.; Sato, F. J. Org. Chem. 1992, 57, 5056
156) Giannis, A.; Snadhoff, K. Angew. Chem. Int. Ed. Engl. 1989, 28, 218 157) Tone, H.; Nishi, T.; Oikawa, Y.; Hikota, M.; Yonemitsu, O. Tetraherdron Lett. 1987, 28, 4569 158) Taber, D.F.; Houze, J.B. J. Org. Chem. 1994, 59, 4004 159) Prasa, A.S.B.; Kanth, J.V.B.; Periasamy, M. Tetrahedron, 1992, 48, 4623 160) J. V. B. Kanth and M. Periasamy, J.Org. Chem. 1991, 56, 5964 161) J. W. Simek et al., J. Chem. Ed. 1997, 74, 107 162) A. I. Meyers, K. Drauz et al., J. Org. Chem. 1993, 58, 3568 163) Giannis, A.; Sandoff, K. Angew. Chem. Int. Ed. Engl.. 1989, 28, 218 164) Dharanipragada, R.; Alarcon, A.; Hruby, V. J. Org. Prep. Prac. Int. 1991, 23, 396 165) Boesten, W.H.; Schepers, C.H.M.; Roberts, M.J.A. EPO 322982 A2 1989 166) Wann, S.R.; Thorsen, P.T.; Kreevoy, M.M. J. Org. Chem. 1981, 46, 2579 167) Abiko, A.; Masamiune, S. Tetrahedron Lett. 1992, 33, 5517
*For Online Consulting Only
175
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
168) Kabno, S.; Tanaka, Y.; Sugino, E.; Hibino, S. Synthesis 1980, 695 169) Ravikumar, K.S.; Shandrasekaran, S. J. Org. Chem. 1996, 61, 826 170) Prasa, A.S.B.; Kanth, J.V.b.; Periasamy, M. Tetrahedron, 1992, 48, 4623 171) Akabori, S.; Takanohashi, Y. J. Chem. Soc..; Perkin Trans 1, 1991, 479 172) Sengupta, S.; Sahu, D.P.; Chatterjee, S.K. Indian J. Chem. 1994, 33b, 285 173) Wann, S.R.; Thorsen, P.T.; Kreevoy, M.M. J. Org. Chem. 1981, 46, 2579 174) Kabno, S.; Tanaka, Y.; Sugino, E.; Hibino, S. Synthesis 1980, 695 175) Prasa, A.S.B.; Kanth, J.V.b.; Periasamy, M. Tetrahedron, 1992, 48, 4623 176) Barby, D.; Champagne, P. Synth. Commun. 1995, 25, 3503 177) Kano, S.; Tanaka, Y.; Sugino, E.; Hibino, S. Synthesis 1980, 695 178) Giannis, A. Sandhoff, K. Angew. Chem. Int. Ed. Engl. 1989, 28, 218
179) Das, B.; Kashinatham, A.; Madhusudhan, P. Tetrahedron Lett. 1998, 39, 677 180) A. Snow, M. Zhao and P.J. Reider et al. (Merck), Tetrahedron Letters. 1997, 38, 2641 181) Barney, C.L.; Huber, E.W.; McCarthy, J.R. Tetrahedron Lett. 1990, 31, 5547 182) Verardo, G.; Giumanini, A.G.; Strazzolini, P.; Poiana, M. Synthesis 1993, 121 183) Verardo, G.; Giumanini, A.G.; Strazzolini, P. Synth. Commun. 1994, 24, 609 184) Vyskocil, S.; Smrcina, M.; Hanus, V.; Polasek, H.; Kocovsky, P. J. Org. Chem. 1998, 63, 7738 185) Brown, H.C. Subba Rao, B.C. J. Am. Chem. Soc. 1959, 81, 6434; Chem. Abstr. 54, 8604f 186) Brown, H.C.; Zweifel, G. J. Am. Chem. Soc. 1966, 88, 1433; Chem. Abstr. 64, 15909a 187) Brown, H. C.; Subba, Rao, B.C. J. Org. Chem. 1957, 22, 1136; Chem. Abstr. 52, 7136c 188) Koester, R. Ann. Chem. 1958, 618, 31; Chem. Abstr. 53, 10014g 189) Koester, R. Angew. Chem. Int. Ed. Engl. 1964, 3, 174 190) Brown, H.C.; Murray, K.J. J. Am. Chem. Soc. 1959, 81, 4108; Chem. Abstr. 54, 5435f
*For Online Consulting Only
176
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
191) Zweifel, G; Brown, H.C.; “Organic Reactions” 1963, 13, 22 J. Wiley and Sons; Chem. Abstr. 60, 7881a 192) Brown, H.C.; Garg, C.P. J. Am. Chem. Soc. 1961, 83, 2951; Chem. Abstr. 56, 9983e 193) Brown, H.C.; Kabalka, G.W.; Rathke, M.W. J. Am. Chem. Soc. 1967, 89, 4530; Chem. Abstr. 67, 99594q 194) Brown, H.C et. al. J. Am. Chem. Soc. 1964, 86, 35654; Chem. Abstr. 61, 11886c 195) Rathke, M.W. et. al. J. Am. Chem. Soc. 1966, 88, 2870; Chem. Abstr. 65, 7072e 196) Honeycutt, Jr. J.B. Riddle, J.M. J. Am. Chem. Soc. 1960, 82, 3051; Chem. Abstr. 55, 5330b 197) Brown, H.C.; Snyder, C.H. J. Am. Chem. Soc. 1961, 83, 1001; Chem. Abstr. 55, 14283e 198) Brown, H.C.; Verbrugge, C.; Synder, C.H. J. Am. Chem. Soc. 1961, 83, 1001; Chem. Abstr. 55, 16392b 199) Brown, H.C.; Rogic, M.M. Organomet. Chem. Syn. 1972, 1, 305; Chem. Abstr. 77, 75239h
200) Brown, H.C.; Midland, M.M. Angew. Chem. Int. Ed. Engl. 1972, 11, 692; Chem. Abstr. 77, 75239h 201) Brown, H.C.; Rathke, M.W. J. Am. Chem. Soc. 1967, 89, 2737; Chem. Abstr. 67, 99562c 202) Brown, H.C.; Rathke, M.W. J. Am. Chem. Soc. 1967, 89, 2738; Chem. Abstr. 67, 99566g 203) Brown, H.C.; Rathke, M.W. J. Am. Chem. Soc. 1967, 89, 2740; Chem. Abstr. 67, 54196v 204) Brown, H.C.; Colman, R.A.; Rathke, M.W. J. Am. Chem. Soc. 1968, 90, 499; Chem. Abstr. 68, 104335h 205) Brown, H.C.; Negishi, E. J. Am. Chem. Soc. 1967, 89, 5478; Chem. Abstr. 68, 21596t 206) Gribble, G.W.; Ferguson, D.C. J. Chem. Soc., Chem. Commun. 1975, 535; Chem. Abstr. 83, 131278h 207) Gribble, G.W.; Heald, P.W. Synthesis 1975, 650; Chem. Abstr. 84, 43791k 208) Umino, N.; Iwakuma, T. Itoh, N. Tetrahedron Lett. 1976, 763; Chem. Abstr. 85, 20719z 209) Gribble, G.W. et. al. J. Am. Chem. Soc. 1974, 96, 7812; Chem. Abstr. 82, 16650r 210) Marchini, P. et. al. J. Org. Chem. 1975, 40, 3453; Chem. Abstr. 83, 20861s
*For Online Consulting Only
177
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
211) Hutchiuns, R.O.; Natale, N.R. J. Org. Chem. 1978, 43, 2299; Chem. Abstr. 89, 5969v 212) Gribble, G.W.; Leiby, R. W.; Sheehan, M.N. Synthesis 1977, 856; Chem. Abstr. 88, 89018z 213) Haire, M.J. J. Org. Chem. 1977, 42, 3446; Chem. Abstr. 87, 183524n 214) Gribble, G.W.; Leese, R.M.; Evans, B.E. Synthesis 1977, 172; Chem. Abstr. 86, 170986u 215) Umino, N.; Iwakuma, T.; Itoh, N. Tetrahedron Lett. 1976, 2875; Chem. Abstr. 86, 16375n 216) Ger. Offen. 2,701,888; Chem. Abstr. 87, 1284194s 217) Maki, Y. et. al. Chem. Lett. 1975, 1093; Chem. Abstr. 83, 192711r 218) Maki, Y. et. al Tetrahedron Lett. 1975, 3295; Chem. Abstr. 83,192758m 219) Maki, Y. et. al Chem. Ind. 1976, 332; Chem. Abstr. 85, 62767u 220) Kikugawa, Y. Chem. Lett. 1975, 1029; Chem. Abstr. 83, 192759n 221) Kikugawa, Y. Chem. Pharm. Bull. 1976, 24, 1059; Chem. Abstr. 85, 108365s
222) Kikugawa, Y.; Yokayama, Y. Chem. Pharm. Bull. 1976, 24, 1939; Chem. Abstr. 86, 43522q 223) Reed, J.W.; Ho, H.H.; Jolly, W.L. J. Am. Chem. Soc. 1974, 96, 1248; Chem. Abstr. 80, 103345x 224) Reed, J.W.; Jolly, W.L. J. Org. Chem. 1977, 42, 3963; Chem. Abstr. 88, 6495d
*For Online Consulting Only
178
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest
IV. ANALYTICAL BOROHYDRIDES
PROCEDURES
FOR
Disclaimer: These methods were developed for internal use by Rohm and Haas and are provided as an aid to our customers and other interested parties. While we believe the information contained herein to be reliable, we assume no liability for its use. It is suggested that the user validate these procedures for his/her own specific needs and samples.
Assay Methods Sodium borohydride may be determined gasometically, the hydrogen evolution method (1-5), or volumetrically (6-9). Jensen (8) lists four volumetric methods of assay: acid and base titration (1), the iodate method (7), a hypochlorite method (6), and a potentiometric titration with permanganate. Sodium borohydride has also been determined volumetrically by an iodine method (2,10), a Chloramine T method (11) and the argentimetric method of Brown and Boyd (12). Other methods that have been reported to be successful include an indirect spectrophotometric
*For Online Consulting Only
method based on the reduction of acetone to isopropyl alcohol (13), a gas chromatographic method based on the reduction of isobutyaldehyde to isobutyl alcohol (2), and a polarographic method (14, 15) Of the above methods, the gasometric or hydrogen evolution method is reported to be the most accurate (13,16, 17). In the volumetric methods, especially those involving oxidation-reductions in acid media, there are two competing reactions: the oxidation-reduction reaction, involving sodium borohydride and the oxidizing species; and the hydrolysis reaction. Harzdoff (9) reports that, in some cases, upon acidification of the alkaline iodate-sodium borohydride solution, gas evolution was observed. For quantitative results using iodometric methods, the borohydride must react with iodine or an iodine complex at a much faster rate than the rate of hydrolysis. The mechanism is reported to be most complicated (18). Lichtenstein (13) reports that results from his indirect spectrophotometric method agree with the hydrogen evolution method. He also reports that the iodate results vary with the concentration of the iodate used. In a Rohm and Haas study (16), the results from the hydrogen evolution technique agreed well with those obtained by the gas
179
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
chromatographic method. The iodate results were 1 to 2 % lower. The method most commonly used at Rohm and Haas for assays are the hydrogen evolution and iodate methods. The hydrogen evolution method is used for finished goods where high accuracy and precision is required. The iodate method is used for inprocess control, in kinetic studies and by customers who do not want to use the hydrogen evolution method since it requires more specialized equipment than is usually available in the laboratory.
solutions used in the assay method. This method will detect as low as 20 ppm of NaBH4. Other methods used successfully for trace borohydride determinations include the NAD+ method (20,21), the crystal violet method (22, 23), the phosphomolybdic acid method (24) and the NBC+ method (25,26) In the NAD+ method, NaBH4 reduces nicotinamide adenine dinucleotide to a UV absorbing species, and the NADH is detected spectrophotometrically at 340 nm. In the crystal violet method, a solution of crystal violet in DMF is employed to titrate an organic solution containing borohydride to a purple end point. In the colorimetric method, phosphomolybdic acid is reduced with sodium borohydride to a blue color. The color can be measured at 665 nm. Table VIII lists the advantages and disadvantages of the various methods used at Rohm and Haas Company.
Trace Methods for Borohydride The hydrogen evolution and iodate methods are both useful for the determination of small amounts of sodium borohydride (2). In the hydrogen evolution method, the 2000-mL reservoir used in the assay method is replaced with a 100-mL gas burette. A confining solution designed to dissolve only small amounts of gas (19) is used in place of water. This method will easily detect 100 ppm NaBH4. In the iodate method, 0.025 N iodate and 0.01 N thiosulfate solutions are used in place of the more concentrated
*For Online Consulting Only
180
Rohm and Haas : the Sodium Borohydride Digest
Table VIII Analytical Methods for NaBH4 Test Method Advantages Disadvantages Assay Hydrogen A highly Requires evolution accurate specialized absolute glassware and method close based on temperature gas laws. control Assay Iodate Rapid Results are method about 1 to 2% Glassware low due to a readily slight available hydrolysis side reaction in the acidification step. Trace 30- Hydrogen Simple, Requires 300 ppm Evolution Fast specialized glassware. Trace 20- Iodate Rapid Other 200 ppm method oxidants and Glassware reductants
*For Online Consulting Only
181
press -F for Searching
Trace 1200 ppm
NAD+
Trace 12000 ppm
Crystal Violet
readily available Rapid, simple method applicable over a wide pH range Rapid, simple method
interfere. Reagent is expensive and unstable. Must be done in aqueous solution. Not applicable to caustic solutions or where strong nucleophiles are present. Has been applied to aqueous and non-aqueous systems.
Rohm and Haas : the Sodium Borohydride Digest
NaBH4 Assay-Hydrogen Evolution Method A. Apparatus See Figure 13. B. Reagents 1) Distilled Water 2) Hydrochloric Acid (6 N)- Mix equal amounts of concentrated HCl and distilled water. C. Procedure 1) Weigh a 3 to 4 g sample of a stabilized water solution of sodium borohydride, or a 0.5 g sample of the dry product to the nearest 0.0001g, into flask F, which is fitted with a rubber stopper. 2) Rinse down column C with a stream of distilled water to remove any acid from a previous run. Dry the inner glass tubing (8 mm O.D. tubing shown in the diagram just below the inner seal of column C) with a paper towel. 3) Fill the 2000-mL bulb G with distilled water through the 20 mL bulb H and then adjust the height of the H-shaped tube until the water level is the same at A and B.
*For Online Consulting Only
press -F for Searching
4) Remove the rubber stopper and immediately attach flask F to the apparatus and secure it with a strong rubber band. 5) Being sure that column C and tubing below the inner seal are dry, vent flask F to the atmosphere by opening and closing the 2 mm stopcock. The water level at A and B should not change. NOTE: If the water level at B drops, add more water through the bulb H. If water overflows at E discard the water. 6) Place a tared 2-liter beaker under E and lower the Hshaped tube until B is at a level with D. No water should overflow at E if the system is airtight and properly adjusted 7) Slowly add through C and the 2 mm stopcock: 10 mL of water, 10 mL of HCl (1:1) and 10m mL of concentrated HCl. Cool flask F momentarily in a water bath whenever the reaction is too vigorous. Do not allow any air into the system through C. Rock the apparatus back and forth to insure completeness of reaction. 8) When gas evolution has ceased, cool flask F to room temperature in a water bath. This will pull water from B back into G. Take enough water from the 2-liter
182
Rohm and Haas : the Sodium Borohydride Digest
beaker and adjust the height of the H-shaped tube so that the water level in B is the same as the water level in the 2000-mL bulb G. 9) Record the temperature of the water in the 2liter beaker. Record the barometer pressure. Record the weight of the water and the 2-liter beaker. The net weight of the water is the weight of water displaced by the hydrogen evolved. % NaBH4 =
W2-W1
-V
D
B-P
15.17
273 + t
W(1000)
W2 = Weight of beaker and contents in grams W1 = Weight of empty beaker in grams D = Density of water at temperature t in grams/mL. V = Volume of water and acid added to flask in mL. t = Temperature of the water in the 2-liter beaker in o C. This should represent the temperature of the system. B = Barometric pressure in millimeters of Hg.
*For Online Consulting Only
press -F for Searching
P = Barometric pressure correction in millimeters of Hg due to the vapor pressure of water at temperature t. A 3 millimeter correction is added to the vapor pressure of water to correct for the difference in expansion of the mercury and the brass scale of the barometer (see Table IX). W = Sample weight in grams Table IX Hydrogen evolution procedure for the determination of NaBH4. Water Barometric Density of Temperature Pressure Water (oC) Correction (-) (g/mL) 15.0 15.8 0.9991 15.5 16.2 16.0 16.6 0.9990 16.5 17.1 17.0 17.5 0.9988 17.5 18.0 18.0 18.5 0.9986 18.5 19.0 19.0 19.5 0.9984 19.5 20.0 20.0 20.5 0.9982
183
20.5 21.0 21.5 22.0 22.5 23.0 23.5 24.0 24.5 25.0 25.5 26.0 26.5 27.0 27.5 28.0 28.5 29.0 29.5 30.0 30.5 31.0
21.0 21.6 22.2 22.8 23.4 24.1 24.7 25.4 26.0 26.7 27.5 28.2 29.0 29.7 30.5 31.3 32.2 33.0 33.9 34.8 35.7 36.7
*For Online Consulting Only
184
press -F for Searching
Rohm and Haas : the Sodium Borohydride Digest
0.9980 0.9978 0.9976 0.9973
31.5 32.0 32.5 33.0 33.5 34.0 34.5 35.0
37.7 38.7 39.7 40.0 41.8 42.9 44.0 45.2
0.9971 0.9968 0.9965 0.9963 0.9960 0.9957 0.9954
Figure 13
0.9951 0.9947 0.9944 0.9941
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
NaBH4 Assay- Iodate Method Warning: Chloroform is a cancer suspect agent A. Generation of iodine in situ: IO3- + 5 I- + 6 H+ Æ 3 I2 + 3 H2O
3.
Reaction with sodium borohydride: BH4- + 4 I2 + 10 H2OÆ B(OH)3 + 8 I- + 7 H30+
4.
Titration of excess iodine with thiosulfate: I2 + 2 S2O3-2 Æ S4O6-2 + 2 I-
5.
B. Reagents 6. 1. 2.
6N H2SO4, Cautiously add 100 mL of concentrated H2SO4 to 500 mL of distilled water while stirring. Mix and cool. Starch Indicator Solution. Mix 4 grams of soluble starch and 10 milligrams of HgI2 with
*For Online Consulting Only
40 mL of distilled water. Add the starch paste, with stirring, to 1000 mL of boiling distilled water. Allow to cool and settle. Use the supernatant liquid. Alternately, 1 mL of chloroform may be used in place of the HgI2. Potassium Iodide. Free Flowing. The highest purity reagent should be used. It should be checked before using, for iodate as follows: dissolve 1g in 25 mL of water; add 2 mL of starch solution and 1 mL of 6 N H2SO4. There should be no immediate appearance of a blue color. If there is the bottle should be rejected. Sodium Hydroxide (1N). Dissolve 40 grams of high purity NaOH pellets in 500 mL of distilled water. Cool. Dilute to one liter. Potassium Iodate (0.25N). Dissolve 8.9173 grams of primary standard KIO3 in freshly boiled and cooled water. Dilute to one liter. Sodium Thiosulfate (0.1N) Dissolve 25 grams of Na2S2O3• 5H2O in one liter of freshly boiled and cooled water. Add 0.1 gram of Na2CO3 to the solution and allow the solution to stand for a day before standardizing. Standardize as follows: Transfer 15 to 18 mL of the standard iodate solution
185
Rohm and Haas : the Sodium Borohydride Digest
to a 250-mL glass stoppered iodine flask. Add 50 mL of distilled water and 2 grams of KI. When the KI has dissolved, add 10 mL of 6 N H2SO4. Titrate with the Na2S2O3 solution to a faint yellow. Add starch indicator solution and continue the titration to the disappearance of the blue color. Calculate the normality for the Na2S2O3 solution as follows. Record to four places behind the decimal. N=
Volume of KIO3, mL x N Volume of Na2S2O3, mL
Alternately, this solution may be standardized against a potassium iodate “standardette” available from Chemical Services Laboratories, P.O. Box 281, Largo, Florida 33540
*For Online Consulting Only
press -F for Searching
186
187
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
1. Procedure for Dry NaBH4 • Weigh a 0.5-gram sample, to the nearest 0.0001g into a stoppered vial and quantitatively transfer to a 250-mL volumetric flask with 1 N NaOH. • Dilute to the mark with 1 N NaOH and mix well. • Pipette a 10.0 mL aliquot into a clean iodine flask and immediately add 35.0 mL of 0.25 N KIO3 solution. • Transfer the iodine flask to a top loading balance and add 2g of KI crystals. Swirl to dissolve KI. • Add 10 mL of 6N H2SO4, stopper, swirl to mix and allow to stand in a cool, dark place for 2 to 3 minutes. • Wash down the stopper and the sides of the flasks with distilled water. Titrate with 0.1 N Na2S2O3, using starch indicator, to a colorless end point.
2. Procedure for aqueous NaBH4 • Weigh a 0.2 to 0.3 gram sample to the nearest 0.0001g into a clean dry stoppered iodine flask containing 10 mL of 1N NaOH • Add 0.25 N KIO3 solution according to the following table:
% NaBH4 = (XN1-YN2) x 11.83 W X = Volume of KIO3, mL N1 = Normality KIO3 Y = Volume of Na2S2O3, mL N2 = Normality Na2S2O3 W = Sample weight in grams
*For Online Consulting Only
Sample size, Grams 0.15 0.20 0.25 0.30
Volume of iodate to be added (mL) 30 35 40 45
• Transfer the iodine flask to a top loading balance and add 2 grams of KI crystals. Swirl to dissolve the KI. • Add 10 mL of 6N H2SO4, stopper, swirl to mix, and allow to stand in a cool, dark place for 2-3 minutes. • Wash down the stopper and the sides of the flask with distilled water. Titrate with 0.1N Na2S2O3, using starch indicator, to a colorless end point.
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
% NaBH4 = (XN1-YN2) x 0.4731 W 2. Legend of symbols : see dry NaBH4
3. Trace NaBH4 Assay-Hydrogen Evolution Apparatus
4.
See Figure 14 1. 2.
Reagents and Solutions Confining solution: Dissolve 200 g of Na2SO4 in a solution composed of 800 mL of water and 40 mL of concentrated H2SO4 Concentrated H2SO4
Procedure: 1. In order to expel all the air from measuring burette (B)- the leveling bulb is raised while stopcock is open. A small amount of confining liquid is expelled to insure absence of air, and stopcock S is then closed. The
*For Online Consulting Only
5. 6. 7. 8.
level in measuring burette should remain constant when leveling bulb is lowered. Weigh a 100 g sample to the nearest 0.0001 g into a 250-mL evolution flask F. Attach the evolution flask F to apparatus with stopcock E open. Close stopcock E and open S to evolution flask. Add 20 mL of concentrated H2SO4 through dropping column D while magnetic stirrer is stirring solution. NOTE: Strength of acid depends on material to be decomposed and hydride to be determined. Keep solution in evolution flask at the same temperature as confining liquid. Read the volume of evolved hydrogen by raising and lowering leveling bulb until its level is the same as the level inside the burette (V2). Record temperature (t) of confining liquid and barometric pressure (B). Run blank on NaBH4 free sample. Record volume displaced, (V1).
188
Rohm and Haas : the Sodium Borohydride Digest
Calculation % NaBH4 = (V2-V1) x (B-3-P)* x 15.17 1000 x (273+t) x W ppm NaBH4 = % NaBH4 x 104 V2 = The volume of gas evolved when sample is reacted, mL V1 = The volume of gas evolved when blank is used, mL B = Recorded barometric pressure in mm of Hg. P = The vapor pressure in mm of the confining solution at the temperature t. See Figure 15. t = Recorded room temperature in oC W = Sample weight in grams. *3 mm are subtracted from the observed barometric pressure to correct for the difference in expansion of the mercury and the brass scale at different temperatures. Exact corrections can be found in any chemical handbook.
*For Online Consulting Only
press -F for Searching
Figure 14
189
Rohm and Haas : the Sodium Borohydride Digest
Figure 15
*For Online Consulting Only
press -F for Searching
190
Rohm and Haas : the Sodium Borohydride Digest
Trace NaBH4 Assay- Iodate Method Generation of iodine in situ: IO3- + 5 I- + 6 H+ Æ 3 I2 + 3 H2O Reaction with sodium borohydride: BH4- + 4 I2 + 10 H2OÆ B(OH)3 + 8 I- + 7 H30+ Titration of excess iodine with thiosulfate: I2 + 2 S2O3-2 Æ S4O6-2 + 2 IA. Reagents and Solutions 1. 2. 3.
0.025 M Potassium Iodate 0.8917g/L 0.01N Sodium Thiosulfate –2.5g/L (NaS2O3•5 H20) Starch solution 4g of soluble starch per liter of boiling distilled water. Use HgI2 or chloroform as a preservative.
*For Online Consulting Only
press -F for Searching
4. 5.
6N H2SO4- 100 mL of concentrated H2SO4 in 500mL of H2O. 1N NaOH –40g/L
B. Procedures: 1. Weigh a 100-gram sample to the nearest 0.0001 g and transfer it to a 500 mL iodine flask with 1N NaOH 2. Add 50-75 mL of H2O (two layers developorganic and an aqueous layer if the sample is organic). 3. Add equivalent amount of 0.025 N KIO3 (1 mL 0.025 N= 0.00012 g NaBH4) plus 10 mL in excess. 4. Add 2 g of potassium iodide and 10 mL of 6N H2SO4 for every 10 mL of 1N NaOH present. 5. Titrate to yellow end point with 0.01 N Na2S2O3, shaking vigorously while titrating. 6. Add 5 mL of starch and continue titration to clear end point. 7. Calculation:
191
Rohm and Haas : the Sodium Borohydride Digest
g NaBH4 =[(V1 x N1) – (V2 x N2)] x 0.004731 g sample Weight of the sample V1 = Volume of KIO3, mL N1= Concentration of KIO3 solution V2= Volume of Na2S2O3, mL N2= Concentration of Na2S2O3 solution ppm NaBH4 = (g NaBH4/ g sample) x 106
*For Online Consulting Only
press -F for Searching
192
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
NaBH4 Trace Assay -NBC
(Nicotinamide Benzyl Chloride)
A. Reagents and Solutions 1. KOH (0.5M)- Prepared by dissolving 3.27 grams of 85 % KOH in water and diluting to one liter. 2. HNO3 (4N, 25 %) 3. Tris(hydroxymethyl)aminomethane (THAM®)-99.9 min 4. Trisbuffer (0.5M)-Prepared by dissolving 6.06 grams of THAM in water and diluting to one liter. The pH is adjusted to 8.5 with 4N HNO3 using a pH meter. 5. Nicotinamide benzyl chloride (NBC)- see section B for synthesis. 6. NBC solution (0.5M) – prepared by dissolving 0.62 grams of NBC in 50 mL of water. 7. NaBH4- high purity (99%). Rohm and Haas Product 8. NaBH4 stock solution (200 µg/mL)- prepared by weighing 20 mg of NaBH4 to the nearest
*For Online Consulting Only
9.
0.0001g into a 100-mL volumetric flask and diluting to the mark with 0.5 M KOH. This solution should be made freshly daily. NaBH4 working solution (20 µg/mL)-Prepared by pipeting 10 mL of the NaBH4 stock solution into a 100 mL volumetric flask and diluting to the mark with 0.5M KOH. This solution should be prepared freshly daily.
B. Synthesis of Nicotinamide Benzyl Chloride (26) 1. Charge a 250-mL round bottom flask, fitted with a drying tube and reflux condenser, with 12.2 g of nicotinamide and 100 mL of methanol (spectrophotometric grade). 2. Dissolve 12.6 g of benzyl chloride in 20 mL of methanol and add to the flask in step 1. 3. Heat the solution under reflux conditions for eighteen hours. 4. Cool the reaction flask to ambient temperature and collect the crystalline salt, which precipitates, on a filter paper.
193
Rohm and Haas : the Sodium Borohydride Digest
5.
Wash the crystals with three 1.5 mL portions of cold (0 oC) methanol and dry to constant weight in a vacuum oven (0.5 mm Hg and 25 o C)
C. Calibration 1. Immediately before use, prepare a reagent mixture of 50 mL of 0.05M NBC and 850 mL of 0.05 THAM buffer. Dispense 85 mL of this mixture into each of six 100-mL volumetric flask. 2. Add 8 mL of 0.05M KOH to each flask. 3. Add 0.0, 1.0, 2.0, 3.0, 4.0 and 5.0 mL of the NaBH4 working solution (20, 40, 60, 80, 100 µg NaBH4) to each flask, dilute to volume with 0.05 M KOH and mix well. 4. Zero the spectrophotometer at 360 nm using the blank (no NaBH4) solution in the 1.0 cm reference and sample cells. 5. After 10 minutes measure the absorbance of each of the standards at 360 nm. 6. Prepare a calibration curve by plotting absorbance versus amount of NaBH4.
*For Online Consulting Only
press -F for Searching
D. Procedure 1. Dispense 85 mL of the THAM/NBC mixture (see C 1) into each of two 100 mL volumetric flasks. 2. Add 8 mL of 0.05 M KOH to each flask. 3. Add up to 5 mL of the sample containing NaBH4 to a 100-mL volumetric flask. Add 5 mL of sample matrix containing no NaBH4 (blank sample) to a second 100-mL flask. 4. Dilute the contents of the flasks to 100 mL with 0.05 M KOH. 5. Measure the absorbance of each solution at 360 nm after 10 minutes. E. Calculations NaBH4 concentration (ppm) = (S-B)( C )(D) W S = absorbance of NaBH4 – treated sample B = absorbance of blank C= slope of calibration curve, µg NaBH4/ absorbance unit D = dilution factor, if any W = Weight of sample in g
194
Rohm and Haas : the Sodium Borohydride Digest
NaBH4 Trace Assay – Crystal Violet Method A. Reagents and solutions 1. Crystal Violet (CV+)- Aldrich 22,928-8, 95 % or equivalent 2. N,N dimethylformamide (DMF)- must be specto -grade. 3. NaBH4- high purity (99 %) Rohm and Haas B. Procedures: 1.Prepare a solution of CV+ in DMF using the following guidelines: Exempted NaBH4 Recommended concentration Concentration, ppm of Crystal Violet Solution 0.019 g CV+ dye diluted to 1.0 L with DMF 200-2000 0.19 g CV+ dye diluted to 1.0 L with DMF NOTE: DMF is a toxic solvent and should be handled with gloves in the hood. Crystal violet is a suspected cancer agent.
*For Online Consulting Only
press -F for Searching
2.
3. 4.
Prepare a standard solution of NaBH4 by dissolving approximately 0.02 g 99% NaBH4 weighed to the nearest 0.0001g in a 100-mL volumetric flask with DMF. Use this solution to standardize the less concentrated CV+ solution. Prepare a more dilute NaBH4 solution by transferring a 10-mL aliquot of the original NaBH4 standard into a 100-mL volumetric flask and diluting to the mark with DMF. Standardize the CV+ solution by titrating a 2.0mL aliquot of each NaBH4 standard with the appropriate CV+ solution to the purple endpoint. Accurately weigh a sample, to the nearest 0.0001g into Erlenmeyer flasks according to the guidelines (see table X)
F= wt of SBH, g x dilution x 2 mL aliquot x 106 µg/g 100 mL (if any) vol of CV+ titrated, mL
5.
Add DMF to solubilize sample (if solid) or to bring total sample and DMF volume to approximately 2-5 mL. Titrate with the appropriate CV+ solution to the first purple endpoint which remains for 60 sec.
195
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
C. Calculations 1. Calculate the concentration of SBH in the sample as follows:
References: 1) Davis, W.D.; Mason, L.S.; Stegeman, G. J. Am. Chem. Soc. 1949, 71, 2775; Chem. Abstr. 43, 7805d 2) Morton Thiokol, inc. Ventron Products, Unpublished standard methods 3) Krynitsky, J.A.; Johnson, J.E.; Carhart, H.W. Anal. Chem. 1948, 20, 311; Chem. Abtsr. 42, 40941 4) Fatt, I.; Tashima, M. “Alkai Metal Dispersions”, D.Van Nostrand Co. , Inc., Princeton, Newy Jersey, 1961, 98 5) Jensen, E.H. “A Study on Sodium Borohydride” Nyt Nordisk Forlag Arnold Busck, Copenhagen 1954, 49 6) Chaikin, S.W. Anal. Chem. 1953, 25, 831; Chem. Abstr. 47, 7371g 7) Lyttle, D.A.; Jensen, E.H.; Struck, W.A. Anal. Chem. 1953, 24, 1843 8) Jensen, E.H. “A Study on Sodium Borohydride” Nyt Nordisk Forlag Arnold Busck, Copenhagen 1954, 49 9) Harzdorf, C.F. Anal. Chem. 1965, 210, 12; Chem. Abstr. 63, 16f 10) Skoblionok, R.F.; Mochalov, K.N.; Berner, B.G. Zh. Anal. Khim. 1968, 23, 1518; Chem. Abstr. 70, 16832d
ppm NaBH4 = F Sample wt, g
Volume of CV+, ml used for sample titration
Where: F = Titer value of the appropriate CV+ titrant, previously calculated in step B 3. Table X Expected NaBH4 Concentration in ppm 0-25 25-50 50-100 100-200
Suggested Sample Weight, g
Expected Volume of Titrant, mL
3 1.5 0.75 0.4
Up to 42.6 21.3-42.6 21.3-42.6 22.7-45.4
200-500 500-1000 1000-2000
1.5 0.75 0.4
17.0-42.6 21.3-42.6 22.7-45.4
*For Online Consulting Only
Recommended CV+ Concentration
0.019g CV+/L
0.19g CV+/L
196
Rohm and Haas : the Sodium Borohydride Digest
11) Shah, A.R.; Padma, D.K.; Murthy, A.R.V. Analyst (London) 1972, 97, 17; Chem. Abstr. 76, 94184g 12) Brown, H.C.; Boyd Jr., A.C. Anal. Chem. 1955, 27, 156; Chem. Abstr. 49, 6031e 13) Lichtenstein, I.E.; Mras, J.S.; J. Fanklin Institute 1966, 281, 481; Chem. Abstr. 65, 6300f 14) Pecsok, R.L. J. Am. Chem. Soc. 1953, 75, 2862; Chem. Abstr. 47, 9817e 15) Gardiner, J.A.; Collat, J. J. Am. Chem. Soc. 1965, 87, 1692; Chem. Abstr. 62, 13899b 16) Morton Thiokol, inc. Ventron Products, Unpublished Report 1967 17) Novakova, A.; Hanovsek, F.; Stuchlik, J. Chem. Prum. 1977, 27, 293; Chem. Abstr. 88, 83074t 18) Freund, T. J. Inorg. Nucl. Chem. 1959, 9, 246; Chem. Abstr. 53, 16665h 19) Kobe, K.A.; Kenton, F.H. Ind. Eng. Chem. Anal. Ed. 1938, 10, 76; Chem. Abstr. 32, 2459
*For Online Consulting Only
press -F for Searching
20) Werner, D.A.; Huang, C.C.; Aminoff, D. Anal. Biochem. 1973, 54, 554; Chem. Abstr. 79, 61169q 21) Morton Thiokol, inc. Ventron Products, Unpublished Report 1976 22) Bunton, C.A.; Huang, S.K.; Paik, C.H. Tetrahedron Lett. 1976, 1445; Chem. Abstr. 85, 108063s 23) Rudie, C.N.; Demko, P.R. J. Am. Oil Chem. Soc. 1979, 56, 520; Chem. Abstr. 90, 214801u 24) Hill, W.H.; Merrill, J.M.; Larsen, R.H.; Hill, D.L.; Heacock, J.F. Amer. Ind. Hyg. Assoc. J. 1959, 20, 5; Chem. Abstr. 54, 13965h 25) Morton Thiokol, inc. Ventron Products, Unpublished Report 1977 26) Beillmann, J.F.; Challot, H.J. Bull. Soc. Chim. Fr. 1968; Chem. Abstr. 69, 59060x
197
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
V. AVAILABILITY
As compared to VenPure SF granules, VenPure AF granules do not contain an anti-caking agent, which adds to its high purity.
Sodium borohydride is available in different forms to satisfy a variety of process needs.
198
VenPure SF powder is a formulation of NaBH4 designed for usage in solvents, like THF, which require a large active surface. A proprietary anti-caking agent is used to increase the product’s flowing characteristics.
VenPure 20/20 solution is an aqueous formulation of NaBH4. It is a pumpable liquid, that contains 20% NaOH to assure transport-stability. VenPure solution is an aqueous formulation containing 40% NaOH, which makes it extremely stable, and suitable for high temperature chemistry.
VenPure AF caplets is a NaBH4 product designed to be dissolved in solvents like water and methanol. The caplets are bean-shaped pellets are about 1 cm long, which allow for a dust-free, straightforward use & handling. It does not contain an anti-caking agent.
Sodium borohydride dry forms (powder, granules and caplets) are shipped in polyethylene bags packed in metal containers. They are classified by DOT regulations as dangerous when wet. Motor freight and or boxcar can ship unlimited quantities.
VenPure SF granules is an NaBH4 product designed for large scale usage in solvents such as ethanol and glymes. The particle size is comparable to table sugar (> 0.5mm), with only small amounts of fines (typically < 3%), which allows for a straightforward use and handling. A proprietary anti-caking agent is used to increase the product’s flowing characteristics.
Sodium borohydride solution is classified as a corrosive liquid under DOT regulations. The material is packaged in 5gallon pails and 55-gallon drums containing 10% free space. Bulk quantities are shipped via tank truck or tank car.
*For Online Consulting Only
199
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
VI. PERSONAL PROTECTIVE EQUIPMENT
Borohydride dust can contaminate personal protective equipment and result in chemical burns -care must be taken to keep equipment clean and serviced
Dry Dry borohydride products are corrosive to eyes, skin and respiratory tract. They will cause irritation or chemical burns if left in contact with moist skin or respiratory tract. Therefore, the use of personal protective equipment is required upon handling. The level of equipment required can vary depending on the expected level of exposure. We recommend : • Chemical goggles • Dust mask and/or a full face shield • Rubber gloves • Coveralls • Rubber boots or closed leather footwear When the potential for exposure is significant, we recommend wearing in addition to the above: • Apron or chemical resistant suit • A NIOSH-approved respirator for corrosive dusts in place of dusk mask
*For Online Consulting Only
Solution Sodium borohydride solutions contain sodium borohydride stabilized with sodium hydroxide. These products are strongly alkaline and corrosive. They can be handled with the same personal protective equipment used when handling 50 % caustic. We recommend the following personal protective equipment when handling the solution form: • Chemical splash goggles and a full face shield • Impervious rubber gloves • Coveralls • Rubber boots with pants over boots (Note : Sodium borohydride solutions are very corrosive to leather)
When handling larger amounts, or when the potential for exposure is greater, a rubber apron or chemical resistant suit can also be worn. If mist is expected, wear a NIOSH – approved respirator for corrosive mists.
200
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
VII. FIRST AID
drinks. Do NOT induce vomiting unless directed by medical personnel. Seek immediate medical attention. Caplets: Give several glasses of water to drink and induce vomiting as directed by medical personnel. Seek immediate medical attention.
Dry Eye contact Immediately flush eyes with copious amounts of water for at least 15 minutes, including under the eyelids. Then seek immediate medical attention. Skin Contact Immediately flush affected area with copious amounts of water for at least 15 minutes. For larger exposures, use an emergency shower. Remove contaminated clothing and shoe. Cleanse skin with soap and water, including hair and under fingernails. Then seek immediate medical attention. Inhalation Remove to fresh air. If symptoms develop, seek immediate medical attention. If not breathing, give artificial respiration. Ingestion Powder/Granules: Rinse mouth with water and give another cupful of water to drink. Do not give carbonated
*For Online Consulting Only
Solution Eye Contact Immediately flush eyes with copious amounts of water for at least 15 minutes, including under the eyelids. Then seek immediate medical attention. Skin Contact Immediately flush affected areas with copious amounts of water for at least 15 minutes. For large exposure, use an emergency shower. Remove contaminated clothing and shoes. Cleanse skin with soap and water, including hair and under fingernails. Seek immediate medical attention. Professionally wash clothing before re-use. Inhalation If mist is inhaled, move to fresh air. Rinse mouth with water. If symptoms develop, seek immediate medical attention. If not breathing, give artificial respiration.
Rohm and Haas : the Sodium Borohydride Digest
Ingestion Give several glasses of water to drink. Do not give carbonated drinks. Do not induce vomiting, seek immediate medical attention. Note to physician: Highly alkaline materials can cause extensive and deep penetrating tissue damage. There is danger of hemorrhage and perforation if lavage is performed. No attempt should be made to neutralize the base with a weak acid.
*For Online Consulting Only
press -F for Searching
201
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
VIII REACTIVITY
examples are polyglycols (2-5% NaBH4) and Dimethyl formamide (over 7% NaBH4)
Dry Dry borohydride products will react violently or explosively in contact with concentrated oxidizers. They will also react vigorously in contact with concentrated acids or under acidic conditions, generating heat and hydrogen gas. Solutions containing borohydride will also react to release hydrogen in the presence of transition metal salts or finely divided metallic precipitates. Dry borohydride products will ignite from a free flame due to hydrogen formation formed by decomposition and will continue to burn as hydrogen is evolved. Dry borohydride products also react with moisture in the air, leading to caking. The moisture will slowly react with the borohydride to liberate hydrogen gas. Some organic solvents, such as acetone and methanol, will react vigorously with borohydride. Other materials can generate heat and liberate hydrogen when high concentrations of borohydride are dissolved or slurried in these materials. Some known
*For Online Consulting Only
Solution NaBH4 solutions will react violently or explosively in contact with concentrated oxidizers. They will also react vigorously in contact with strong acids or under acidic conditions, generating heat and hydrogen gas. Solutions containing borohydride will also react to release hydrogen in contact with transition metal salts or finely divided metallic precipitates. Sodium borohydride solution will also react violently with aluminum due to the sodium hydroxide present in the solution. In addition, material as sensitive polymerization under alkaline conditions, such as acrylonitirle and ethylene oxide, may polymerize upon contact with sodium borohydride solution. This solution is also incompatible with ammonia also. General Consideration In all cases where borohydride products are used, some H2 generation is expected. In many cases, H2 can be safely vented to the outside of the building. H2 should not be allowed to collect in a closed area.
202
Rohm and Haas : the Sodium Borohydride Digest
For reaction vessels, use N2 blanking to prevent an explosive atmosphere from forming. Under ambient temperature and pressure, N2 will prevent such conditions, as long as O2 concentration is below 5%. The use of explosion proof equipment is recommended.
*For Online Consulting Only
press -F for Searching
203
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
IX. FIRE FIGHTING/ FLAMMABILITY
surface. Disturbing the surface too soon can cause the hot material to reignite.
Dry Dry borohydride products are flammable solids and are classified by the U.S. DOT as Division 4.3Dangerous when wet and the NFPA as a class 1 dust. Fires involving dry sodium borohydride products should be controlled with dry chemical extinguishers: recommended dry chemical agents are sodium bicarbonate based, monoammonium phosphate based or equivalent. Do not use water, carbon dioxide or halogen type fire extinguishers. Sand, dolomite or lime should also be available in case the dry chemical agent is insufficient or in windy conditions. Firefighters and others who may be exposed to the products of combustion should be equipped with NIOSH-approved positive pressure self-contained breathing apparatus (SCBS) and full protective clothing. Once the fire is extinguished, add additional smothering agents such as dolomite, dry sand or lime. Allow the material to cool before disturbing the *For Online Consulting Only
Solution Sodium borohydride solution is nonflammable. Any flammability is due to hydrogen generation upon decomposition. Under normal storage conditions, it is extremely stable, decomposing less than 0.01% per year. To prevent pressure buildup, 10% free volume is required for all closed containers, under these conditions, containers will normally generate less then 1 psig per year.
204
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
X. SPILL AND WASTE DISPOSAL
hazardous waste with the code D002-corrosive. Check with local regulations and guidelines for additional requirements.
Dry In the U.S., spills and wastes of dry sodium borohydride products are regulated by the U.S. EPA’s Resource Conservation and Recovery ACT (RCRA) as a hazardous waste with the code D003-reactive and D001-Ignitable. Check with local regulations and guidelines for additional requirements. When dry borohydride products are spilled, clean-up personnel must wear appropriate personal protective equipment. Use non-sparking tools or explosion proof equipment to shovel or vacuum material into an appropriate container for disposal as hazardous waste. After removing the spill from the floor, the area should be rinsed with water, and the rinse water collected for disposal. Solution In the U.S. spills and wastes of borohydride solution products are regulated by the U.S. EPA’s Resource Conservation and Recovery Act (RCRA) as a
*For Online Consulting Only
In the event of an accidental spill, immediate steps should be taken to : 1.) contain the spill, 2.) absorb the spill using an absorbent 3.) remove the spilled material for disposal. Proper procedures and protective equipment should by employed as outlined in the section “Personal Protective Equipment.” Spills of solution should be prevented from entering any sewer or streams. Dams can be constructed by using sand, dolomite, or other absorbent material. Solution spills can be transferred to a container for disposal. All remaining liquids should be absorbed using the material mentioned above and then placed in a container for disposal. If permitted by regulatory authorities borohydride wastes, spills and rinse water streams can be neutralized and hydrolyzed on site prior to discharge. This can be
205
Rohm and Haas : the Sodium Borohydride Digest
accomplished by adding the borohydride to a large excess of water followed by the slow addition of dilute acid to a neutral pH. Hydrogen gas will evolve, therefore be sure the area is well ventilated and all sources of ignition are eliminated. If the spill occurs indoors, adequate ventilation should be maintained prior to proceeding with containment, cleaning and disposal. After removing the spill, the area should be rinsed with water and the rinse water collected for disposal. If the spill occurs outdoors, any contaminated soil should be removed and placed into a container for proper disposal. Empty drums and lines should be disposed of as industrial waste in accordance with local regulations.
*For Online Consulting Only
press -F for Searching
206
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
XI. TOXICITY Dry Dry sodium borohydride powder and caplets have an acute dermal LD50 on dry skin of 4000 –8000 mg /kg and are not skin sensitizers. Toxicity is increased in the presence of moisture and can result in severe irritation and skin burns. The acute oral LD50 of sodium borohydride powder or caplets is 69-mg/kg. This product is considered toxic under FHSA classifications. The acute oral LD50 of potassium borohydride powder is 160-mg/kg. This product is considered toxic under FHSA classifications.
*For Online Consulting Only
Solution Solution of sodium borohydride in 50 % caustic has a dermal LD50 of 100-500 mg/Kg and is considered moderately toxic. This is primarily attributed to caustic soda, which can cause skin burns and irritation. The acute oral LD50 of the SWS solution is 500-1000 mg/kg. This product is considered toxic under FHSA classifications. Sodium borate, the product form the reaction or decomposition of sodium borohydride, is considered slightly toxic orally (LD50; 2000-4000mg /kg) and nontoxic dermally (LD50 8000 mg/kg).
207
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
XII. STORAGE AND HANDLING Dry
Solution
Dry borohydrides products are hydroscopic and should not be unnecessarily exposed to moisture. Any contact with moisture will result in hydrogen evolution. They will remain stable indefinitely in dry air or sealed containers. Dry borohydride products should be stored in closed containers in a dry, cool, well ventilated area and kept separated from oxidizers, acids and other incompatible materials. Store only in original containers as received or in properly marked plastic bottles, do not store in glass due to the potential for pressure buildup and rupture. Also do not store in aluminum containers. This applies to the product as received or any make-up thereof. Empty containers can be hazardous, following label warnings even after container is emptied since they may retain product residues. Do not re-use empty container without professional cleaning for food, clothing, or product for human or animal consumption or where skin contact can occur.
Sodium borohydride solution can be stored and handled in the same manner as 50 % caustic. Sodium borohydride solution may be stored in adequately ventilated mild steel, stainless steel, polyethylene or fiberglass vessels suitable for caustic storage. As with caustic, Aluminum equipment must not be used with sodium borohydride solutions. Store only in original containers as received or in properly marked plastic bottles. Do not store in glass due to the potential for pressure buildup and rupture and the corrosive nature of sodium hydroxide on glass. This applies to the product as received or any make-of thereof. Under normal conditions storage, the decomposition of sodium borohydride solutions is less then 0.01% per year. One of the decomposition products is hydrogen. All closed containers of sodium borohydride solution should have at least 10% free volume and should be checked periodically. If this is followed, pressure buildup will be less then 1 psig per year at normal storage temperatures.
*For Online Consulting Only
208
Rohm and Haas : the Sodium Borohydride Digest
Sodium borohydride solution can be stored in stainless steel, mild steel, and approved fiberglass vessels. Stainless (316 SS or 304 SS) is recommended for piping, valves, pumps, etc. Sodium borohydride solution must not be stored in vessels that react with caustic soda, such as aluminum. Sodium borohydride solution should be stored at temperatures between 65o F (18o C) and 100o F (37o C) for ease of handling. Below 65o F the solution viscosity increases rapidly, and at temperatures below 55o F (13o C), crystallization can occur. If crystallization occurs, liquefy by slowly warming to 70-90o F (21-32o C) while venting. Do not use live steam. Heating above 100o F is not recommended due to the increased decomposition at these temperatures. Transfer piping exposed to cold temperature should be heat traced and/or insulated. Precaution should be taken to avoid overheating the piping, as excessive line pressure and/ or product decomposition may result.
*For Online Consulting Only
press -F for Searching
209
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
XIII. SHIPPING Dry
Solution
For transport purpose, dry borohydride products are designated as hazardous material under U.S. DOT, IATA/ICAO and IMO as follows:
For transport purposes sodium borohydride solutions are designated as a hazardous material under U.S. DOT, IATA/ICAO and IMO as follows:
Proper Shipping Name: Sodium Borohydride (Potassium Borohydride)
Proper Shipping Name: For less then 1000 lb. (454 kg) of NaOH: Sodium borohydride and Sodium Hydroxide solution For 1000 lb. (454 kg) or more of NaOH: RQ, Sodium borohydride and Sodium Hydroxide Solution
Hazard Class/ ID Number: 4.3/UN 1426 for NaBH4 (4.3/ UN 1870 for KBH4)
Hazard Class/ Id Number: 8/ UN3320
Packing Group:I Packaging Group: II Label: Dangerous when wet Label: Corrosive
*For Online Consulting Only
210
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
Disclaimer: To the best of our knowledge the information contained herein is correct. All products may present unknown health hazards and should be used with caution. Although certain hazards are described herein, we cannot guarantee that these are the only hazards which exists. Final determination of suitability of the product is the sole responsibility of the user. Users of the products should satisfy themselves that thee conditions and methods of use assure that the product is used safely. NO REPRESENTAIONS OR WARRANTIES, EITHER EXPRESSED OR IMPLIED, OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE OR ANY OTHER NATURE ARE MADE HERE UNDER WITH REPECT TO THE NFORMATION CONTAINED HEREIN OR THE PRODUCT TO WHICH THE INFROMATION REFERS. Nothing herein is intended as a recommendation to use our products so as to infringe any patents. We assume no liability for customer’s violation of patents or other rights. The customer
should make his own patent investigation relative to his proposed use.
*For Online Consulting Only
211
Rohm and Haas : the Sodium Borohydride Digest
press -F for Searching
Please feel free to send us your questions via
[email protected], or contact one of our offices : in America: Rohm and Haas Company S&PA 60 Willow Street Phone: 1-978-557-1832 Fax: 1-978-557-1879
in Asia: Rohm and Haas China, Inc. 23rd Floor, Hitech Plaza No. 488 S. Wu Ning Road Shanghai, China Phone: +86 21 6230 6366 Fax: +86 21 6230 6377
Updated information can be found at : http://www.hydridesolutions.com/
*For Online Consulting Only
in Europe: Rohm and Haas France S.A. la tour de Lyon 185, rue de Bercy F-75579 Paris Phone: +33-1 4002 5210 Fax : +33-1 4002 5441
212