Photochemistry of Diazonium Salts. 5. Syntheses of 2,4-Difluoroimidazole-5-carboxylic Acid and Related Compounds

Article abstract of DOI:10.1021/jo00185a023

Catalytic hydrogenolysis, effective for the synthesis of 2-aminoimidazoles from 2-(arylazo)imidazoles, cannot be used to prepare 2-amino-4-fluoroimidazoles because the fluorine atom is lost simultaneously; formamidinesulfinic acid, however, achieves the required conversion in good yield.Ethyl 2,4-difluoroimidazole-5-carboxylate is obtained by photolysis of ethyl 2-diazonio-4-fluoroimidazole-5-carboxylate in fluoroboric acid.The ester is saponified to the acid in 1 N base (without loss of fluorine) but is stable in 0.05 N base; the ester also resists ammonolysis to the carboxamide or hydride reduction to the carbinol.Ammonolysis of ethyl 2-amino-4-fluoroimidazole-5-carboxylate is successful, however, and the resulting carboxamide is converted, via diazotation and photolysis, into 2,4-difluoroimidazole-5-carboxamide.N-Alkyl derivatives of the difluoro ester undergo facile hydride reduction of the ester function, but only with prior reductive loss of fluorine at C-2.The difluoro acid is stable to diborane reduction over 1 month.These examples of resistance to normal carboxyl modification are ascribed to the facile generation of the imidazolate ion in basic media and a resulting large increase in electron density at the carbonyl carbon by resonance overlap.