Unexpected Hydrolysis of 5‐Aminoisoxazolbenzoylamide Herbicide Isoxaben into 5‐Isoxazolinone

Abstract

AbstractThe benzoylamide derivative of 5‐aminoisoxazol, i.e. the herbicide isoxaben 1 (N‐[3‐(1‐ethyl‐1‐methylpropyl)isoxazol‐5‐yl]‐2,6‐dimethoxybenzamide) was transformed by aqueous acid hydrolysis into the unexpected 5‐isoxazolinone 3 (3‐(1‐ethyl‐1‐methylpropyl)isoxazolin‐5–one) plus mainly 2,6‐dimethoxybenzamide 4. The expected 5‐aminoisoxazol 7 (5‐amino‐3‐(1‐ethyl‐1‐methylpropyl)isoxazol) was not generated, except in very low amounts when high acid concentrations were used. In separate hydrolysis trials made in similar aqueous acid conditions, it was observed that the 5‐aminoisoxazol 7 and 5‐isoxazolinone 3 were not transformed. The 5‐isoxazolinone 3 formed by isoxaben 1 acid hydrolysis thus was the first generated product, and was not formed by the consecutive nucleophilic substitution of 5‐aminoisoxazol 7 which would have been formed in a first step. This unexpected 5‐amino C‐N bond cleavage by nucleophilic attack of H2O at the 5‐C of the isoxazol ring of isoxaben 1 ‐instead of the usual amide CO‐N bond cleavage‐ probably is due to the positive charge existing at the 5‐C atom of the isoxazol ring. The acid hydrolysis pathway observed for isoxaben 1 also is the main soil metabolism pathway. The absence of formation of an aromatic amino compound by chemical hydrolysis reduces the concern as to their potential tranformation into carcinogenic nitroso or azo compounds in soil. On the other hand, isoxaben 1 was not hydrolyzed in aqueous dilute alkali.