One-pot synthesis of 4-methyl-2-alkyl quinazoline-N-oxides by cascade acetamidation–acylation of simple electron-rich arenes with primary nitroalkanes

Abstract

A one-pot, two-stage reaction sequence leading to 2,4-dialkylquinazoline-3-oxide derivatives has been developed. It begins with the in situ formation of anilides by the Beckmann-type acetamidation of simple, bearing electron-donating groups arenes with primary nitroalkanes in polyphosphoric acid. Subsequent acylation with nitroethane results in the corresponding oximes that react with the neighboring, previously introduced o-anilide moiety to afford the target cyclic N-oxide. Thus, the precursors for this procedure are easily accessible electron-rich arenes unlike the cycloaddition pathways described in the literature that rely almost entirely on o-aminoarylketones whose synthetic and commercial availability is somewhat limited.