New Histamine and Histidine Analogues via Transformations of the 2-Trifluoromethyl Group

Article abstract of DOI:10.1021/jo01307a020

α-N-Benzoyl-2-(trifluoromethyl)histamine has been transformed, via a difluorodiazafulvene intermediate, into 2-carboxy- and 2-(carbomethoxy)histamine. 2-Carboxy-L-histidine was prepared by a similar route. 2-(Carbomethoxy)-L-histidine was prepared by methanolysis of α-N-(tert-butoxycarbonyl)-2-(trifluoromethyl)-L-histidine and acid hydrolysis of the intermediate ortho ester. 2-Cyanohistamine and 2-cyano-L-histidine are best prepared by ammonolysis of the corresponding α-N-(tert-butoxycarbonyl)-2-(trifluoromethyl)imidazoles and acid cleavage of the protecting group.During the hydrolysis of N-benzoyl protecting groups in hot, aqueous mineral acid, decarboxylation of 2-carboxyimidazoles occurs gradually; this side reaction is repressed by use of concentrated acid.