3-Methylcarboxy-1H-Indazole. Theoretical Study of Its Formation via Intramolecular Aliphatic Diazonium Coupling and X-Ray Crystal Structure
The methyl ester of 1H-indazole-3-carboxylic acid (2-Me) is formed in the diazotization of o-aminophenylacetic acid to o-diazoniumphenylacetic acid (1) in an intramolecular aliphatic diazonium coupling. 2-Me was identified and characterized by single-crystal x-ray diffraction and found to crystallize as hydrogen-bonded trimers of crystallographically independent molecules. The methylcarboxy groups are rotated slightly out of the best plane of the trimer resulting in only a pseudo-threefold axis. The crystal structure of 2-Me is compared with other indazoles and pyrazole. Regioselective electrophilic diazonium ion addition to the enol tautomer of 1 and subsequent hyrazone-azo tautomerization are proposed as a possible mechanism for indazole formation under acidic conditions. The tautomerization equilibrium between acetic acid and its enol 1,2-dihydroxyethene was studied and the effects of phenyl and o-diazoniumphenyl substitution on this equilibrium were explored with semi-empirical quantum mechanical methods. The performance of the semi-empirical method was assessed by comparison with ab initio and/or experimental data. It was found that the enol of o-diazoniumphenylacetic acid is stabilized greatly owing to extended conjugation and push-pull interactions in the enol form. These results suggest that the enol tautomer might be a viable reactive intermediate that warrants considerations in discussions of reaction mechanisms.
R. Glaser et al., "3-Methylcarboxy-1H-Indazole. Theoretical Study of Its Formation via Intramolecular Aliphatic Diazonium Coupling and X-Ray Crystal Structure," Journal of Physical Organic Chemistry, vol. 6, no. 4, pp. 201-214, Wiley-Blackwell, Apr 1993.
The definitive version is available at https://doi.org/10.1002/poc.610060403
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