Microwave-assisted synthesis in water: first one-pot synthesis of a novel class of polysubstituted benzo[4,5]imidazo[1,2-b]pyridazines via intramolecular SNAr

Abstract

A novel and straightforward one-pot synthesis protocol has been developed for the synthesis of benzo[4,5]imidazo[1,2-b]pyridazines through intramolecular S_NAr, utilizing water as a green solvent and microwaves as an efficient green energy source. The entire strategy consists of just one step; reaction between 3-oxo-2-arylhydrazonopropanals which contain o-fluorine substituent on the N-aryl ring of the arylhydrazone moieties with active methylene compounds, including 3-oxo-3-phenylpropionitrile, 3-oxo-3-hetarylpropionitrile, ethyl cyanoacetate and 2-cyanoacetamide giving the target compounds in an overall yield of 89–99%. The reaction is carried out under microwave irradiation as well as under conventional heating. The factors affecting the optimization of the reaction are examined in detail. X-ray crystallographic analysis was used to establish the structures and regioselectivity of the reaction.