FLUORINE REACTIVITY IN 2-(TRIFLUOROMETHYL)IMIDAZOLES

2-(Trifluoromethyl) imidazole undergoes facile alkaline hydrolysis to imidazole-2-carboxylic acid (in 0.1 N KOH at 30°C, t1/2 = 5.8 h), the 4-methyl derivative being 12-fold as reactive as the parent compound. The rate-limiting step is the solvent-assisted internal elimination of fluoride ion from the imidazolate anion to give a transient difluorodiazafulvene. Formation of the carboxylic acid is retarded by addition of fluoride ion, demonstrating the reversibility of the elimination step. Alcoholysis to orthoesters involves the same difluorodiazafulvene intermediate but is 200-fold slower than hydrolysis because of the weaker solvating power of alcohols. In alkaline media, the triethyl orthoester loses a molecule of alcohol to form the moderately stable diethoxydiazafulvene. Protonation of the imidazole ring retards acid hydrolysis of the orthoesters 60-fold relative to trialkyl orthobenzoates. 2-(Trifluoromethyl)imidazoIes are converted directly to 2-cyanoimidazoles (90% yield) in aqueous ammonia; as in hydrolysis and alcoholysis, formation of the difluorodiazafulvene is rate limiting. The value of kobsd for cyanoimidazole formation increases with the water content of the ammonia solution and follows the rate law kobsd = kr[H2O]n(fIm-), with n=5.0. The reactivity of the trifluoromethyl group is lost following N-alkylation of the imidazole ring. © 1979, American Chemical Society. All rights reserved.