Catalyst-Free, Glycerol-Assisted Facile Approach to Imidazole-Fused Nitrogen-Bridgehead Heterocycles

A completely regioselective, environmentally benign strategy for the facile synthesis of biologically important imidazole-fused nitrogen-bridgehead heterocycles has been developed using glycerol/water 4:1 as a green promoting media. The methodology involves the simple coupling of 2-halocarbonyl compounds with 2-aminopyridines, 2-aminopyrimidines, 2-aminopyrazines to obtain a variety of 2-aryl substituted imidazo-pyridines, imidazo-pyrimidines and imidazo-pyrazines containing bridgehead nitrogen. This protocol eliminates the use of toxic catalysts and volatile organic solvents - two key principles in the development of a green chemical process. Other significant highlights include mild reaction conditions, operational simplicity, short reaction times, easy workup and purification process, high yields and potential for scale-up.