Alcohols by reduction of carboxylic acids

PREPARATION OF ALCOHOLS BY REDUCTION OF CARBOXYLIC ACIDS AND ESTERS... 

Sources of Alcohols 615 Preparation of Alcohols by Reduction of Aldehydes and Ketones 617 Preparation of Alcohols by Reduction of Carboxylic Acids 620 Preparation of Alcohols from Epoxides 620... 

Section 15.3 Alcohols can be prepared from carbonyl compounds by reduction of carboxylic acids and esters. See Table 15.3. 

In a more general sense, this reduction method provides a convenient pathway for converting an aromatic carboxyl group to a methyl group (see Table I).7 Previously, this transformation has been achieved by reduction of the acid to the alcohol with lithium aluminum hydride, conversion of the alcohol to the tosylate, and a second reduction either with lithium aluminum hydride [Aluminate(l —), tetrahydro, lithium,... 

With most reducing agents, reduction of carboxylic acids generally gives the primary alcohol (19-34) and the isolation of aldehydes is not feasible. However, simple straight-chain carboxylic acids have been reduced to aldehydesby treatment with Li in MeNH2 or NH3 followed by hydrolysis of the resulting imine, ... 

From oxidative cleavage of 1,2-diols and 1,2-amino alcohols Dibutyltin oxide, 95 By reaction of alkyl halides with sulfur-stabilized carbanions Methylthiomethyl p-tolyl sulfone, 192 From reduction of carboxylic acids Vilsmeier reagent, 341 From terminal alkenes by addition reactions... 

Reduction then proceeds by successive transfers of hydride ion, H e, from aluminum to carbon. The first such transfer reduces the acid salt to the oxidation level of the aldehyde reduction does not stop at this point, however, but continues rapidly to the alcohol. Insufficient information is available to permit very specific structures to be written for the intermediates in the lithium aluminum hydride reduction of carboxylic acids. However, the product is a complex aluminum alkoxide, from which the alcohol is freed by hydrolysis ... 

Aldehydes are intermediate ill oxidation level, and thus the aldehyde functional group can be installed by either reduction of carboxylic acid derivatives or oxidation of alcohols. Aldehydes are rarely installed without a change of oxidation level. One difficulty is that they undergo both oxidation and reduction readily. Special methods are required to stop at the aldehyde stage rather than proceeding by further reduction or oxidation. 

The conversion of carboxylic acids to aldehydes is normally conducted in two steps by reduction of the acids or their derivatives to the corresponding alcohols followed by mild oxidation. 

Functional Group Transformation Alcohols can be prepared by nucleophilic substitution of alkyl halides, hydrolysis of esters, reduction of carboxylic acids or esters, reduction of aldehydes or ketones, electrophilic addition of alkenes, hydroboration of alkenes, or substitution of ethers. 

In summary, reductions of carboxylic acid derivatives to primary alcohols are usually accomplished by reaction of esters or acids with lithium aluminum hydride. The following equations provide several examples ... 

Reduction of carboxylic acids with borane-dimethyl sulfide generally proceeds rapidly In connection with reduction experiments with p-hydroxybenzoic acid, it was found that this compound gave only low yields of p-hydroxybenzyl alcohol when treated with borane-dimethyl sulfide according to the procedure described by Knstersson et al (1980) This is in accordance with studies of the... 

Selective reduction of—COOH to —CH2OH.2 Chemoselective reduction of carboxylic acids is possible by in situ conversion to the carboxymethyleneiminium salt by reaction with the Vilsmeier reagent (DMF and oxalyl chloride). This salt is then reduced with NaBH4 (2 equiv.) to the alcohol (equation I). Various functional groups are tolerated bromo, cyano, ester, and C=C (even when conjugated to COOH). 

An attractive feature of BH3 THE and BH3 SMe2 is the facile reduction of carboxylic acids to primary alcohols. The reduction involves initial formation of a triacylborate with concomitant evolution of 3 H2, followed by fast hydride transfer to the carbonyl carbon to furnish, after workup, the corresponding primary alcohol. 

Alcohols from acids. After formation of 0-acylureas by reaction of carboxylic acids with Af.N -dicyclohexylcarbodiimide, reduction leads to the alcohols. 

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