Hydrogen-deuterium exchange carboxylic acids

If a carbanion is thermodynamically accessible, but is subject to rapid quenching by internal return of C02 in the case of decarboxylation, or by a proton in carboxylation, or in a hydrogen/deuterium exchange reaction, then the carbanionic intermediate off the enzyme would give the appearance of greater basicity than its thermodynamic value would predict. The localized character of the carbanion at the 6-position of UMP requires that the proton that is removed by a base in solution initially remains closely associated, and therefore, to a great extent be transferred to the carbanion. This reduces the rate of exchange and creates a discrepancy between kinetic and thermodynamic acidities. 

Imtdazo[4,5-c]pyridtne, 4,5,6,7-tetrahydro-synthesis, 5, 623, 640, 641 Imidazo[4,5-c]pyridine-6-carboxylic acid, 4,5,6,7-tetrahydro-synthesis, 5, 623, 641 Imidazopyridines as anthelmintic, 1, 202 synthesis, 5, 462 Imidazo[l,2-n]pyridines deuterium exchange, 5, 611 diazo coupling, 5, 614 Dimroth rearrangement, 5, 613 halogenation, 5, 611 hydrogenation, 5, 614 Mannich reaction, 5, 612 nitration, 5, 612 1-oxides... 

The hydrogen atoms of the methyl and carboxyl groups of 1 -phenyl-3-methylpyrazole-5-carboxylic acid are replaced by deuterium under mildly alkaline conditions.538 No other example of hydrogen exchange in a methylpyrazole seems to have been recorded. 

Superacid DF-SbFs induces protium-deuterium exchange in isobutane [54b]. Strong acids (BF3, BFj-HjO, HF-BFj, CF3SO3H)catalyze carbonylation of alkanes including methane by carbon monoxide [54c], whereas sulfuric acid can induce carbonylation of iso- and cycloalkanes [54e,d]. In both cases, carboxylic acids are obtained. The elimination of molecular hydrogen from alkyl can occur (see a recent theoretical study of the Hz elimination from CzHs [54f]). 

The enolates of aldehydes and ketones undergo deuterium exchange, bromination, and alkylation reactions (Sections 22.4—22.6). Carboxylic acid derivatives react similarly. However, the added possibility of a competing nucleophilic acyl substitution reaction limits some of the substitution reactions at the a-carbon atom of acid derivatives. For example, acyl halides react with most bases in substitution reactions at the carbonyl carbon atom rather than by abstraction of the a-hydrogen atom. On the other hand, the pA of the a-hydrogen atoms of amides is very large, and these derivatives would require a very strong base for formation of enolates for synthetic reactions. Esters are the most convenient acyl derivatives for enolate formation and subsequent substitution at the a-carbon atom. The substituted ester can subsequently be converted into other acyl derivatives. 

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