Carboxylic acids, reduction with LiAlH

Alternatively, borane in tetrahydrofuran (BH/THF) is a useful reagent for reducing carboxylic acids to primary alcohols. Reaction of an acid with BH3/THF occurs rapidly at room temperature, and the procedure is often preferred to reduction with LiAlH because of its relative ease, safety, and specificity. Borane reacts with carboxylic acids faster than with any other functional group, thereby allowing selective transformations such as that shown below on p-nitrophenylacetic acid. If the reduction of p-nitrophenyl-acetic acid were done with LiAlH4, both nitro and carboxyl groups would be reduced. 

Conversion of Amides into Amines Reduction Like other carboxylic acid derivatives, amides can be reduced by LiAlH.4. The product of the reduction, however, is an amine rather than an alcohol. The net effect of an amide reduction reaction is thus the conversion of the amide carbonyl group into a methylene group (C=0 —> CTbV This kind of reaction is specific for amides and does not occur with other carboxylic acid derivatives. 

The final step is to convert the carboxylic acid into a primary alcohol by heating it with lithium aluminium hydride (LiAlH ) dissolved in ether (ethoxyethane). This is a reduction reaction and delivers the target molecule, propan-l-ol. 

Selective reduction of functional groups can be achieved by chemical modification of the LiALH4 for example, lithium tri(t-butoxy)aluminium hydride [LiAIH(t-OBu)3] is a more selective reagent, and reduces aldehydes and ketones, but slowly reduces esters and epoxides. Nitriles and nitro groups are not reduced by this reagent. Carboxylic acids can be converted into the aldehyde via acid chloride with lithium tri(tert-butoxy) aluminium hydride at a low temperature (—78°C). The nitro compounds are not reduced under this condition. Thus, selective reduction of 3,5-dinitrobenzoic acid (6.45) to 3,5-dinitrobenzaldehyde (6.47) can be achieved in two steps. First, 6.45 is converted into 3,5-dinitrobenzoyl chloride (6.46) and then LiAlH(t-OBu)3 reduction of 6.46 gives 6.47. 

For example, reduction of acid chlorides (RCOCl), prepared from carboxylic acids by reaction between the acid and, for example, thionyl chloride (vide infra), with hydrogen over a barium sulfate (BaS04) poisoned palladium (Pd) catalyst (the Rosenmund reduction), can often be used to produce the corresponding aldehyde (RCHO). The same product can more easily be obtained from the same starting material by using commercially available lithium aluminum tri-r-butoxy hydride (LiAlH[OC(CH3)3]3) in an ether solvent,such as bis(2-methoxyethyl)ether [diglyme, (CH30CH2CH2)20], at -78°C (Scheme 9.106). 

The rationale for this reaction is similar to that given earlier for the reduction of acids by LiAlH. The first step is reaction with the proton of the carboxylic... 

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