Cleavage of Diethyl Chromonyl α-Aminophosponate with Nitrogen and Carbon Nucleophiles: A Synthetic Approach and Biological Evaluations of a Series of Novel Azoles, Azines, and Azepines Containing α-Aminophosphonate and Phosphonate Groups

A convenient synthetic approach leading to a series of novel substituted azoles, azines, and azepines linked to the alpha-aminophosphonate moiety was achieved. The methodology depends on ring opening and ring closure (RORC) of the chromone ring of diethyl chromonyl alpha-aminophosphonate 1 via its reaction with nitrogen nucleophiles such as primary amines and 1,2-, 1,3-, and 1,4-bi-nucleophiles in ethanolic sodium ethoxide. Also, treatment of compound 1 with some acyclic and cyclic active methylene compounds under the same reaction conditions afforded interesting novel isolated and fused pyridine systems bearing phosphonate groups at the alpha-position. The screening of antimicrobial activity for the synthesized compounds indicates that connection of pyrazole, oxazepine, and benzodiazepine rings with alpha-aminophosphonate moiety exhibited good antimicrobial effects. Also, evaluation of their antioxidant properties shows that the compounds having 1,5-benzoxazepinyl and 1,5-benzodiazepinyl units in combination with alpha-aminophosphonic diester moiety are the most powerful antioxidant agents.