Reduction of Aromatic Carboxylic Acids

Aromatic carboxylic acids can be reduced to aldehydes or alcohols. In addition, a carboxylic group linked to an aromatic ring can be converted to methyl, and the aromatic ring can be partially or totally hydrogenated. 

Aldehydes are obtained in 86% and 75% yields, respectively, from benzoic acid on refluxing for 6 hours and from nicotinic acid on standing at room temperature for 24 hours with bis(N-methylpiperazino)alane in tetrahydro-furan [963]. Reduction of 3-fluorosalicylic acid with 2% sodium amalgam in aqueous solution containing sodium chloride, boric acid and p-toluidine gave, at 13-15°, a Schiff base which on hydrolysis with hydrochloric acid and steam distillation afforded 3-fluorosalicylaldehyde in 57% yield [136. The purpose of p-toluidine is to react with the aldehyde as it is formed and protect it from further reduction. 

Reduction of aromatic carboxylic acids to alcohols can be achieved by hydrides and complex hydrides, e.g. lithium aluminum hydride 968], sodium aluminum hydride [55] and sodium bis 2-methoxyethoxy)aluminum hydride [544, 969, 970], and with borane (diborane) [976] prepared from sodium borohydride and boron trifluoride etherate [971, 977] or aluminum chloride [755, 975] in diglyme. Sodium borohydride alone does not reduce free carboxylic acids. Anthranilic acid was reduced to the corresponding alcohol by electroreduction in sulfuric acid at 20-30° in 69-78% yield [979], 

Saturation of the aromatic rings in aromatic carboxylic acids takes place 

Sodium in liquid ammonia and ethanol reduced benzoic acid to 1,4-dihy-drobenzoic acid. Reduction of p-toluic acid was more complicated and afforded a mixture of cis- and rranj-l,2,3,4-tetrahydro-p-toluic acid and cis-and tra j-l,4-dihydrotoluic acid. m-Methoxybenzoic acid yielded 1,2,3,4-tetrahydro-5-methoxybenzoic acid, and 3,4,5-trimethoxybenzoic acid gave l,4-dihydro-3,5-dimethoxybenzoic acid in 87% yield (after hydrogenolysis of the methoxy group para to carboxyl) [984. In the case of 4 -methoxy-biphenyl-4-carboxylic acid, sodium in isoamyl alcohol at 130° reduced completely only the ring with the carboxylic group, thus giving 92% yield of 4-(p-methoxyphenyl)cyclohexanecarboxylic acid [955]. 

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METHYL GROUPS BY REDUCTION OF AROMATIC CARBOXYLIC ACIDS 83... 

The reduction of aromatic carboxylic acids to the corresponding aldehydes under aerobic conditions is of interest in biotechnology, since the oxidoreductase from Nocardia sp. is able to accept a range of substituted benzoic acids, naphthoic acids, and a few heterocyclic carboxylic acids (Li and Rosazza 1997). The reaction involves formation of an acyl-AMP intermediate by reaction of the carboxylic acid with ATP NADPH then reduces this to the aldehyde (Li and Rosazza 1998 He et al. 2004). A comparable reaction for aromatic carboxylates has been demonstrated in Neurospora crassa (Gross 1972). 

Scheme 23 Cathodic reduction of aromatic carboxylic acids to benzyl alcohols or benzaldehydes.

Rabideau PW, Wetzeland DM, Young DM. Metal-ammonia ring reduction of aromatic carboxylic acid esters. J Org Chem 1984 49 1544-1549. 

Lane CF, Myatt HL, Daniels J, Hopps HB (1974) Organic synthesis using borane-methyl sulfide II Reduction of aromatic carboxylic acids in the presence of tnmethyl borate J Org Chem 39 3052-3054... 

There has been considerable research into the electrolytic reduction of aromatic carboxylic acids to the corresponding aldehydes. A general procedure has been described in which key elements are the use of the ammonium salt of the acid, careful control of the pH and the presence of an organic phase (benzene) to extract the aldehyde and thus minimize overreduction. The method appears to work best for relatively acidic substrates for example, salicylaldehyde was obtained in 80% yield. Danish workers have shown that, under acidic conditions, controlled electrolytic reductions are possible for certain pyridine-, imidazole- and thiazole-carboxylic acids. In these cases, it is thought that the product aldehydes are protected by geminal diol formation. A chemical method which is closely related to electrolysis is the use of sodium amalgam as reductant. Although not widely used, it was successfully employed in the synthesis of a fluorinated salicylaldehyde. ... 

Eour-electron reductions of aromatic carboxylic acids occur when reactions are carried out in strongly acidic solutions at lead or mercury cathodes, giving excellent yields of the corresponding benzyl alcohols [23,34-36]. The reaction is easily performed on a large scale. For example, the adaptation of a filter press cell for continuous reduction of benzoic acid has been described [37]. 

The reduction of aromatic carboxylic acids by Na(Hg) may take place in the nucleus or in the carboxyl group. Phthalic acid is reduced to m w-3,5-cyclohexadiene-l,2-dicar-boxylic acid [102] or 2,5-cyclohexadiene-l,2-dicarboxylic acid [103], whereas certain phenolic carboxylic acids may be reduced to aldehydes. 

Methyl groups by reduction of aromatic carboxylic acids with trichbrosilane-tri-n-propylamine.2 In a hood well vented to permit open atmospheric transfer of trichloro-silane and to remove hydrogen chloride off gas produced, a 300-ml. three-necked. 

Rare earth oxides have been studied to a lesser extent than alkaline earth oxides. However, they show characteristic selectivity in the dehydration of alcohols. Secondary alcohols form 1-olefins, whereas the same reaction over an acid catalyst produces the thermodynamically more stable 2-olefin (312). An example of an industrially important rare earth oxide catalyst is Zr02. It has several applications, including the reduction of aromatic carboxylic acids with hydrogen to aldehydes (314), the dehydration of 1-cyclohexyl ethanol to vinyl cyclohexane (315), and the production of diisobutyl ketone from isobutyraldehyde (316). The extensive use of Zr02 is mainly due to its resistance to poisoning by H2O and CO2, and its inherent catalytic activity is a result of its bifunctional acid-base properties. It contains both weakly acidic and basic sites, neither of which is susceptible to poisoning. The acid-base functionality of Zr02 is displayed in the reaction of alkylamine to nitrile (278) (Fig. 33). To form nitriles from both secondary and tertiary amines, both acid and base sites are required. 

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