Irreversible Conjugation of Aldehydes in Water To Form Stable 1,2,4-Oxadiazinan-5-ones

A new, irreversible aldehyde conjugation reaction in aqueous media was developed. α-Aminooxy acetohydrazides undergo irreversible condensation reactions with aliphatic, aromatic, or unsaturated aldehydes and isatins in a mixture of acetonitrile and acetate buffer at pH 4 to yield 1,2,4-oxadiazinan-5-one heterocycles in excellent isolated yields (40-99%). This class of heterocycles proved to be hydrolytically stable throughout a wide range of temperatures and pH (4.5-7).