An Unusual Trifluoromethyl Elimination Reaction from the 4,4-Bis(trifluoromethyl)-5-hydroxyimidazoline Ring System

A facile detrifluoromethylation was observed when 4,4-bis(trifluoromethyl)-5-hydroxyimidazoline 5 was treated with a variety of bases to afford the biologically interesting 4-(trifluoromethyl)imidazole analogs (9 and 10). A unique mechanism was proposed for this transformation, supported by isolating and trapping the hypothesized intermediates. Heating of 5 with Et₄NCN in DMSO provided 19, which was clearly derived from the proposed intermediate 17. Finally, imidazole 9 was converted into the N-[2-phenyl-4-(trifluoromethyl)-1H-imidazol-5-yl]-N-methylbenzamide analogs, which were potential acyl CoA:cholesterol acyltransferase (ACAT) inhibitors.