A Theoretical Study on the Tautomerism of C-Carboxylic and Methoxycarbonyl Substituted Azoles

Abstract

DFT calculations (B3LYP/6-31+G * * ) have been carried out on 106 tautomers and conformers of NH-azoles bearing CO 2 H and CO 2 CH 3 groups. The following azoles systems have been studied: 2-substituted pyrroles, 2-substituted indoles, 2-substituted imidazoles, 2-substituted benzimidazoles, 4(5)-substituted imidazoles, 3(5)-substituted pyrazoles, 3-substituted indazoles (1H and 2H), 3,4(5)-substituted-1,2,3(5)-triazoles, 2,3(5)-substituted-1,2(3),4-triazoles, 4(5)-1,2,3,4(5)-tetrazoles. In the case of pyrazole, 3,5-disubstituted derivatives have also been computed, including four dimers.

Revisiting the Structure and Chemistry of 3(5)-Substituted Pyrazoles

“…A similar effect was observed for other pyrazoles bearing a substitution pattern prone to interact intramolecularly. In this case, interactions in study were between C-carboxyl or methoxycarbonyl groups and the hydrogen at N1, which were also shown to stabilize the less stable 5-tautomer [68].…”

Interplay of thermochemistry and Structural Chemistry, the journal (volume 16, 2005) and the discipline

“…Additionally DFT calculations were performed. While the enthalpy of formation of various 1H-imidazoles has been measured [147], no corresponding data exists for any of their 2H-isomers [148,149]. Enthalpies of activation for the rearrangement of 2,2-spiro(cycloalkane) and 2,2-di(p-substituted benzylated 2H-imidazoles) have been reported [150].…”

“…The aim of the article by Alkorta and Elguero [148] was designed to study the influence of the carboxylic acid and its methyl ester substituents on the tautomerism of azoles using DFT calculations. While the enthalpy of formation of numerous such species have long been known, it was only in the year preceding the publication of the current review that it was measured for the parent pyrrole-2-carboxylic acid and its N-methyl derivative [152].…”

Interaction of N‐Heterocyclic Carbenes and Simple Carbenes with Small Molecules (One to Three Atoms) Excluding Metals: Formation of Covalent C–X Bonds

“…It is known from old that azole‐carboxylic acids present tautomerism between neutral N and zwitterionic forms ZW (a pseudo‐cross‐conjugated heterocyclic mesomeric betaine ). For the annular tautomerism of pyrazole‐3(5)‐carboxylic acids, see (compound 30N is a 3‐substituted tautomer).…”