Energetic Effect of the Carboxylic Acid Functional Group in Indole Derivatives.

The standard molar enthalpy of formation, in the gaseous phase, at T = 298.15 K, was calculated by combining, for each compound, the standard molar enthalpy of formation, in the crystalline phase, and the standard molar enthalpy of sublimation, yielding -(222.2 ± 3.5) kJ·mol-1 and -(234.1 ± 2.1) kJ·mol-1 for indole-3-carboxylic acid and 1-methylindole-3-carboxylic acid, respectively. Computational studies, at the G3(MP2) composite level, were conducted for indole-3-carboxylic acid and 1-methylindole-3-carboxylic acid as a complement of the experimental work, and they were also extended to the remaining isomers, indole-2-carboxylic acid, 1-methylindole-2-carboxylic acid, 3-methylindole-2-carboxylic acid, and 2-methylindole-3-carboxylic acid, to provide reliable estimates of the corresponding thermochemical parameters. The agreement of the estimates of the standard gas-phase enthalpy of formation so obtained, indole-2-carboxylic acid -(223.6 ± 0.8) kJ·mol-1, 1-methylindole-2-carboxylic acid -(223.7 ± 0.8) kJ·mol-1, 3-methylindole-2-carboxylic acid -(251.6 ± 1.0) kJ·mol-1, indole-3-carboxylic acid -(227.1 ± 1.1) kJ·mol-1, 1-methylindole-3-carboxylic acid -(238.0 ± 1.0) kJ·mol-1, and 2-methylindole-3-carboxylic acid -(267.2 ± 1.0) kJ·mol-1, with the available experimental data gives us additional confidence for the situations not studied experimentally. The enthalpic effect resulting from the entrance of the carboxyl group into the indole ring was discussed, and an enthalpic stabilization was found for indole and pyrrole derivatives when compared with other similar systems.