Reduction of Aliphatic Carboxylic Acids

The reduction of free acids to alcohols became practical only after the advent of complex hydrides. Lithium aluminum hydride reduces carboxylic acids to alcohols in ether solution very rapidly in an exothermic reaction. Because of the presence of acidic hydrogen in the carboxylic acid an additional equivalent of lithium aluminum hydride is needed beyond the amount required for the reduction. The stoichiometric ratio is 4 mol of the acid to 3 mol of lithium aluminum hydride (Equation 12, p. 18). Trimethylacetic add was reduced to neopentyl alcohol in 92% yield, and stearic acid to 1-octadecanol in 91% yield. Dicarboxylic sebacic acid was reduced to 1,10-decanedioI even if less than the needed amount of lithiiun aluminum hydride was used [968]. 

Another reagent, sodium bis 2-methoxyethoxy)aluminum hydride (Vitride), was used to reduce nonanoic acid to 1-nonanol in refluxing benzene in 92% yield [969]. The same reagent converts sodium or bromomagnesium salts of acids to alcohols sodium stearate to 1-octadecanol at 80° in 96% yield, and bromomagnesium octanoate to 1-octanol at 80° in 85% yield [970]. 

Sodium borohydride does not reduce the free carboxylic group, but borane prepared from sodium borohydride and boron trifluoride etherate in tetrahydrofuran converts aliphatic acids to alcohols at 0-25° in 89-100% yields 

Carboxylic acids containing double bonds are easily converted to saturated acids by catalytic hydrogenation over common catalysts. If a new chiral center is generated in the reduction process, homogeneous hydrogenation over a chiral catalyst gave 40-45% enantiomeric excess of one enantiomer [19], 

Lithium aluminum hydride reduces exclusively the carboxyl group, even in an unsaturated acid with a, -conjugated double bonds. Sorbic acid afforded 92% yield of sorbic alcohol [968], and fumaric acid gave 78% yield of trans-2-butene-l,4-diol [97S]. If, however, the a, -conjugated double bond of an add is at the same time conjugated with an aromatic ring it is reduced (p. 141). 

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Appropriate activation of carboxyl groups enables reduction of aliphatic carboxylic acids to the corresponding aldehydes. The electroreduction of iminium salts prepared from aliphatic carboxyKc... 

Recently, the electrolysis of aliphatic carboxylic acids in an undivided cell and in the presence of triphenyl phosphine has been reported, which turned out to be one of the most reliable methods for the reduction of aliphatic carboxylic acids to the corresponding aldehydes (Scheme 26) [11, 52]. In this reaction. 

Scheme 26 Cathodic reduction of aliphatic carboxylic acids in the presence of triphenylphosphineto aldehydes R alkyl, aryl, yields 36 -100%.

Deoxygenation of carbonyl compounds. Hydrous Sn02 is prepared from SnCU by precipitation with aqueous ammonia then drying and calcination at 300°C for 5 h. The reduction of aliphatic carboxylic acids gives the corresponding alcohols, whereas aromatic acids are further reduced to the hydrocarbons. Aromatic ketones also give hydrocarbons. 

Reductions. Lane has reviewed reductions with BMS. He notes that this reagent is somewhat less reactive than BH3 THF and usually requires a temperature of 20-25°. He recommends that the reagent be added at this temperature. Reduction of aliphatic carboxylic acids proceeds readily, but reduction of benzoic acids is slow unless trimethyl borate is added. The reagent reduces acids, esters, oximes, nitriles, and amides, but does not reduce halides or nitro groups. 

Because of the highly negative reduction potentials ( —3.0 V vs. SCE) [32], the electroreduction of esters of aliphatic carboxylic acids to primary alcohols by direct electron transfer from the cathode is very difficult and the electrochemical Birch-type reduction of aliphatic esters in MeNH2 or liquid NH3 has not been reported until recently (Scheme 15) [33, 34]. This reaction is not a reduction by direct electron transfer from the cathode to the C=0 bonds of the ester but the reduction by a solvated electron. 

Acetonitrile, 407 Acetophenone, 725,729,730 phenylhydrazone, 852 p-Acetotoluidide, 593, 605 Acetoxime, 343 Acetylacetone, 861, 862, 863 Acetylation, reductive, 749 Thiele, 749 Acetyl chloride, 367 2-Acetylcyciohexanone, 862, 864 Acetylene, 245, 897 reactions of, 245, 246 Acetylenic compounds, synthesis of, 467-469, 895-902 Acetylglycine, 909 Acetylmethylurea, 968, 969 Acetylsalicylio acid, 996 Acetyl-o-toluidide, 578 2-Acetylthiophene, 837 Acid anhydrides of aliphatic carboxylic acids, 371... 

A selective, mild, and facile reduction of aromatic and aliphatic carboxylic acid imida-zolides to primary alcohols is described in reference [33]. The reaction proceeds in water, water/dioxane or water/tetrahydrofuran solution at room temperature with 2-5 molar equivalents of NaBH4 in about 1 h. 

Aliphatic carboxylic acids are difficult to reduce electroehemically. Reduction of a 10% oxalic acid in 10% H2SO4. at 15 °C at a mercury cathode (Refs. [494, 532] in Ref. [29]), a lead or amalgamated lead cathode (Ref. [495] in Ref. [29]) or at a sodium amalgam (Na(Hg) cathode (Ref. [497] in Ref. [29]) produces glyoxylic acid with a material yield of 88% and a current efficiency of 70%. The glyoxylic acid formed is stabilized by hydration [29]. 

Scheme 25 Cathodic reduction of activated aliphatic carboxylic acids to aldehydes (R alkyl, yields 70-82%) and ketones (R benzyl, yields 66- 72%).

A large number of stable /e-organo tellurocarboxylates were prepared from tellurolates and aliphatic1,2 or aromatic2 carboxylic acid chlorides or aliphatic carboxylic acid anhydrides . The tellurolates were obtained by reduction of diorgano ditelluriums with sodium borohydride. 

Bis(N-inethylpiperazinyl)aluniinum hydride (li. This hydride was originally prepared from aluminum hydride and N-methylpiperazine, and was used to reduce carboxylic acids directly to aldehydes. It can be prepared more conveniently from lithium aluminum hydride and the amine. It is useful for reduction of aliphatic and aromatic acids to aldehydes (80-95% yield). Significantly, it reduces a,p-unsaturated acids to aldehydes without reduction of the double bond (70-80% yield). ... 

Aliphatic carboxylic acids are reducible to the alcohol in low yield in strongly acidic electrolytes. Thus, phenylacetic acid is reduced to 2-phenylethanol in 25-50% yield at a lead cathode in 50% sulfuric acid-ethanol [39] and butyric acid to butanol in 80% sulfuric acid in 6.5% yield [40]. The latter conversion can also be performed in 17% yield in 7% aqueous sodium hydroxide, despite the fact that the carboxylate form of the acid, which is reducible only with difficulty, predominates in bulk solution, suggesting an electrocatalytic reduction involving specific interaction of the substrate and electrode surface. 

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