Synthesis of quinazoline-3-oxides via a Pd(ii) catalyzed azide–isocyanide coupling/cyclocondensation reaction

Abstract

A novel and efficient protocol concerning palladium catalyzing the three-component reaction of 2-azidobenzaldehyde, isocyanide, and hydroxylamine hydrochloride is developed. This method allows the rapid elaboration of quinazoline 3-oxides in a one-pot fashion. The 3-CR mainly involves concatenation of azide–isocyanide denitrogenative coupling, condensation with hydroxylamine and 6-exo-dig cyclization. The salient features of the methodology are operational simplicity, use of milder reaction conditions, being devoid of any additives such as oxidants (redox neutral) or base, and releasing N₂ and H₂O as the byproducts.