Alumina catalyzed transamidation of primary amides with amines: experimental and computational approaches

Abstract

New favipiravir analogs with high efficiency as a drug molecule was designed and synthesized to meet the global challenge of COVID-19. A computational approach has been applied for the screening and optimization of favipiravir derivatives. The synthesis of virtually screened favipiravir analogs by transamidation of primary amides using Al2O3 as a heterogeneous catalyst was carried out during the the research. The catalyst, primary amide and amines in a 1:1 (mmol) ratio with different solventswere optimized to established the reaction.By using this catalyst benzylamine and o-toluidine were successfully incorporated by transamidation reaction to the favipiravir molecule.Favipiravir derivatives (i) N-benzyl-6-fluoro-3-hydroxypyrazine-2-carboxamide and (ii)6-fluoro-3-hydroxy-N-(o-tolyl)pyrazine-2-carboxamidewere synthesized.Al203 showed the highest catalytic activity for the synthesis of favipiravir derivatives in comparison with SnO2, Cu2O, Nb2O5, CeO2, TiO2. Synthesized favipiravir derivatives showed more effectiveness as drug candidates compared to favipiravir where a unique and sustainable technique was developedfor the transamidation of primary amides with amines employing Al2O3 as a reusable, affordable, and commercially available heterogeneous catalyst that is tolerant of basic molecule coexistence.

Key words: Favipiravir, amide, amine, transamidation, Al2O3, heterogeneous catalyst.