Methylene group modifications of the N-(Isothiazol-5-yl)phenylacetamides. Synthesis and insecticidal activity

It has been shown that oxidation at the alpha-carbon of N-(4-chloro-3-methyl-5-isothiazolyl)-2-[p-[(alpha,alpha, alpha-trifluoro-p-tolyl)oxy]phenyl]acetamide (1) is conveniently brought about using dimethylformamide dimethylacetal to give N-(4-chloro-3-methyl-5-isothiazolyl)-beta-(dimethylamino)-p-[(alpha, alpha,alpha-trifluoro-p-tolyl)oxy]atropamide (2), which has served as a common starting point for a variety of functional group transformations. These transformations were found to proceed in moderate to good yields to give derivatives of 1 that retained much of the efficacy associated with the parent amide and have allowed for an expansion of the SAR to be developed. Examples of enamines, enols, enol (thio)ethers, oximes, and hydrazones were prepared. In particular, the enamines derived from low molecular weight amines and amino acids were most active as broad-spectrum insecticides and were found to be even more active than 1 on root-knot nematode.