Carboxylic acids carboxyl groups reduction

From a study of the decompositions of several rhodium(II) carboxylates, Kitchen and Bear [1111] conclude that in alkanoates (e.g. acetates) the a-carbon—H bond is weakest and that, on reaction, this proton is transferred to an oxygen atom of another carboxylate group. Reduction of the metal ion is followed by decomposition of the a-lactone to CO and an aldehyde which, in turn, can further reduce metal ions and also protonate two carboxyl groups. Thus reaction yields the metal and an acid as products. In aromatic carboxylates (e.g. benzoates), the bond between the carboxyl group and the aromatic ring is the weakest. The phenyl radical formed on rupture of this linkage is capable of proton abstraction from water so that no acid product is given and the solid product is an oxide. 

Carboxylic Acid Group. Reactions of the carboxyl group include decarboxylation, reduction to alcohols, and the formation of salts, acyl hahdes, amides, and esters. 

Generally, the carboxyl group is not readily reduced. Lithium aluminum hydride is one of the few reagents that can reduce these organic acids to alcohols. The scheme involves the formation of an alkoxide, which is hydroly2ed to the alcohol. Commercially, the alternative to direct reduction involves esterification of the acid followed by the reduction of the ester. 

Reactions of the carboxyl group include salt and acid chloride formation, esterification, pyrolysis, reduction, and amide, nitrile, and amine formation. Salt formation occurs when the carboxyUc acid reacts with an alkaline substance (22)... 

Although the nitro group plays a crucial role in most of these SrnI reactions, reactions of this type have synthetic application beyond the area of nitro compounds. The nitromethyl groups can be converted to other functional groups, including aldehydes and carboxylic acids.Nitro groups at tertiary positions can be reductively removed by reaction with the methanethiol anion.This reaction also appears to be of the electron-transfer type, with the methanethiolate anion acting as the electron donor ... 

A thioamide of isonicotinic acid has also shown tuberculostatic activity in the clinic. The additional substitution on the pyridine ring precludes its preparation from simple starting materials. Reaction of ethyl methyl ketone with ethyl oxalate leads to the ester-diketone, 12 (shown as its enol). Condensation of this with cyanoacetamide gives the substituted pyridone, 13, which contains both the ethyl and carboxyl groups in the desired position. The nitrile group is then excised by means of decarboxylative hydrolysis. Treatment of the pyridone (14) with phosphorus oxychloride converts that compound (after exposure to ethanol to take the acid chloride to the ester) to the chloro-pyridine, 15. The halogen is then removed by catalytic reduction (16). The ester at the 4 position is converted to the desired functionality by successive conversion to the amide (17), dehydration to the nitrile (18), and finally addition of hydrogen sulfide. There is thus obtained ethionamide (19)... 

Scheme 4 outlines the synthesis of key intermediate 7 in its correct absolute stereochemical form from readily available (S)-(-)-malic acid (15). Simultaneous protection of the contiguous carboxyl and secondary hydroxyl groups in the form of an acetonide proceeds smoothly with 2,2 -dimethoxypropane and para-toluene-sulfonic acid and provides intermediate 26 as a crystalline solid in 75-85 % yield. Chemoselective reduction of the terminal carboxyl group in 26 with borane-tetrahydrofuran complex (B H3 THF) affords a primary hydroxyl group that attacks the proximal carbonyl group, upon acidification, to give a hydroxybutyrolactone. Treat-... 

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,... 

The photo-Kolbe reaction is the decarboxylation of carboxylic acids at tow voltage under irradiation at semiconductor anodes (TiO ), that are partially doped with metals, e.g. platinum [343, 344]. On semiconductor powders the dominant product is a hydrocarbon by substitution of the carboxylate group for hydrogen (Eq. 41), whereas on an n-TiOj single crystal in the oxidation of acetic acid the formation of ethane besides methane could be observed [345, 346]. Dependent on the kind of semiconductor, the adsorbed metal, and the pH of the solution the extent of alkyl coupling versus reduction to the hydrocarbon can be controlled to some extent [346]. The intermediacy of alkyl radicals has been demonstrated by ESR-spectroscopy [347], that of the alkyl anion by deuterium incorporation [344]. With vicinal diacids the mono- or bisdecarboxylation can be controlled by the light flux [348]. Adipic acid yielded butane [349] with levulinic acid the products of decarboxylation, methyl ethyl-... 

Glycosyl-linkages were determined by GC-EIMS of the partially methylated alditol acetates. RG-II samples (2 mg) were methylated using sodium methyl sulfmyl carbanion and methyl iodide in dimethyl sulfoxide [24] followed by reduction of the uronosyl groups with lithium triethylborodeuteride (Superdeuteride , Aldrich) [23,25]. Methylated and carboxyl-reduced samples were then submitted to acid hydrolysis, NaBIlt reduction and acetylation, partially methylated alditol acetates being analysed by EIMS on two fused-silica capillary columns (DB-1 and DB-225) [20]. 

Reduction of uronic acids Uronic acids (UA) were converted to the corresponding neutral sugars (NS) by carbodiimide activation of the carboxyl groups followed by a reduction with NaBD4 according to the method of Kim and Carpita [5]. In order to achieve a complete reduction of the uronic acids the procedure was repeated once. 

If only the O-H, as opposed to the carbonyl, of a carboxyl group has to be masked, it can be readily accomplished by esterification. Alkaline hydrolysis is the usual way for regenerating the acid. t-Butyl esters, which are readily cleaved by acid, can be used if alkaline conditions must be avoided. 2,2,2-Trichloroethyl esters, which can be reductively cleaved with zinc, are another possibility.267 Some esters can be cleaved by treatment with anhydrous TBAF. These reactions proceed best for esters of relatively acidic alcohols, such as 4-nitrobenzyl, 2,2,2-trichloroethyl, and cyanoethyl.268... 

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