Synthesis of 4-hydroxy-3,4-dihydro-1,2,3-benzotriazines via 2-(3-alkyl-1-triazeno)benzaldehydes and 2-(3-alkyl-1-triazeno)benzophenones

Abstract

Diazotization of o-aminobenzaldehyde, followed by immediate coupling of the diazonium salt with primary alkylamines, affords unstable l-aryl-3-alkyltriazenes which immediately cyclize to the 4-hydroxy-3-alkyl-1,2,3-benzotriazines. Analogous reaction of o-aminobenzophenones affords stable 4-aryl-4-hydroxy-3-alkyl-1,2,3-benzotriazines. The 4-hydroxytriazine derived from o-anthraniloylbenzoic acid undergoes further cyclization spontaneously to a novel spiro-1,2,3-triazine-furan. Diazotization of o-aminopropiophenone and coupling to methylamine affords a surprisingly stable 4-alkyl-4-hydroxytriazine. Preliminary assay of the biological activity of the 4-hydroxytriazines shows significant cytotoxicity of two members of the series towards M21 melanoma cells in vitro.