Reactivity of 1,3-dipoles in aqueous solution. Part 1. Stereospecific formation of Z-amidoximes in the reaction of benzonitrile oxides with amines

Abstract

Nitrile oxides (3) are rapidly generated in situ on dissolution of the corresponding hydroxamoyl chlorides (1) in aqueous solution at pH > 4; reaction of (3) with the solvent is slow at pH < 10. Primary and secondary amines react stereospecifically to give only the Z-amidoximes (11), in which the nucleophile and OH groups are cis. With primary amines and ammonia the Z-isomer is also thermodynamically favoured but with the more bulky secondary amines subsequent isomerisation to the more stable E-isomer (12) occurs. Several criteria (ρ+0.53 for substituent variation in the nitrile oxide; β_nuc 0.48 for primary amine variation; small enhancement shown by ‘α-effect’ amines; small steric effect of ortho-substituents in nitrile oxide) are consistent with a transition state for amidoxime formation in which there is little bond formation between the amine and the carbon of the nitrile oxide.