Pyrrole-2-carboxylic acid, mechanism decarboxylation

Scheme 9 Mechanism of decarboxylation via addition of water to the carboxyl group of pyrrole-2-carboxylic acid. Reprinted with permission from Reference 73. Copyright 2009 American Chemical Society.

We have presented evidence that pyrrole-2-carboxylic acid decarboxylates in acid via the addition of water to the carboxyl group, rather than by direct formation of C02.73 This leads to the formation of the conjugate acid of carbonic acid, C(OH)3+, which rapidly dissociates into protonated water and carbon dioxide (Scheme 9). The pKA for protonation of the a-carbon acid of pyrrole is —3.8.74 Although this mechanism of decarboxylation is more complex than the typical dissociative mechanism generating carbon dioxide, the weak carbanion formed will be a poor nucleophile and will not be subject to internal return. However, this leads to a point of interest, in that an enzyme catalyzes the decarboxylation and carboxylation of pyrrole-2-carboxylic acid and pyrrole respectively.75 In the decarboxylation reaction, unlike the case of 2-ketoacids, the enzyme cannot access the potential catalysis available from preventing the internal return from a highly basic carbanion, which could be the reason that the rates of decarboxylation are more comparable to those in solution. Therefore, the enzyme cannot achieve further acceleration of decarboxylation. In the carboxylation of pyrrole, the absence of a reactive carbanion will also make the reaction more difficult however, in this case it occurs more readily than with other aromatic acid decarboxylases. 

The mechanisms of the acid-catalysed decarboxylation of pyrrole-2-carboxylic acid and mesitoic acid have been investigated at the B3LYP/6-311G (d, p) level of theory. A polarizable continuum model has been established in order to evaluate the effects of solvents on these reactions. The results of the calculations indicate that the first step of the acid-catalysed decarboxylation of the pyrrole-2-carboxylic acid has two possible pathways the proton of H30 attacks either the a-carbon atom or the carboxyl oxygen atom. The subsequent process of forming a four-membered ring TS is the ratedetermining step. The computational results show that both pathways are favoured. 

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