Preparation of N-heterylarenes from the perspective of phenylhydrazine-based under the principles green chemistry

Abstract

Herein, modern green synthesis approaches are studied to assemble N-heterylarenes scaffolds via a non-catalyzed intramolecular 5/6-exo-dig cyclocondensation reaction based on the in-situ generation of arenehydrazonopentan-/hexan-2-one. Accordingly, the formation of two N-heteryl moieties, pyrazol-1-yl and pyridazin-1(4H)-yl, was initially studied. Therefore, appropriate fluorophenyl was first converted into their respective phenylhydrazine by SNAr reaction and then reacted with different trigonal carbonyl bielectrophiles (-CO-, -CO2R, and -CO2H) in ethanol in the presence of US, MW, IR, and an IR· US irradiation mixture. Cyclic nitrogenous cores were best obtained when subjected to microwave irradiation with ketone and arylhydrazine as starting reagents, allowing them to get excellent yields quickly. Arylhydrazine reactants featuring Π-donor groups underwent the best 5/6-exo-dig type annulment reaction. Presumably, the observed improvements in EDG-dependent reaction efficiency reflect changes in the nucleophilicity of arylhydrazines intermediates as α-nucleophilic reactants.