N-ALKYL-N-(5-ISOTHIAZOLYL)-PHENYLACETAMIDES AND N-(ALKYLISOTHIAZOLIN-5-YLIDENE)-PHENYLACETAMIDES - SYNTHESIS AND BIOLOGICAL-ACTIVITY

Treatment of 5-amino-4-chloro-3-methylisothiazole (3) with the acid ch loride of ha,alpha,alpha-trifluoro-p-tolyl)oxy]phenyl]acetic acid (6) afforded the amide hloro-3-methyl-5-isothiazolyl)-2-[p-[(alpha,alpha, alpha-trifluoro-p-tolyl)oxy]phenyl]acetamide (1), which was substitute d with various alkyl groups in an effort to alleviate toxicity toward non-target organisms through a proinsecticide approach. Alkylations of 1 under a variety of reaction conditions afforded two major products which were derived from amide-nitrogen substitution, N-alkyl-N-(4-chlo ro-3- lpha,alpha-trifluoro-p-tolyl)oxy]phenyl]acetamides (a), and ring -nitrogen substitution, -4-chloro-3-methyl-3-isothiazolin-5-ylidene)-2 -[p- [(alpha,alpha,alpha-trifluoro-p-tolyl)oxy]phenyl] acetamides(8). Derivatives 7 and 8 were found to exhibit lessened toxicity to trout a s well as insects, but, in general, efficacy toward insects was retain ed to a greater degree. In particular methoxymethyl, ethoxymethyl, eth yl, and ethyl-d(5) substituents demonstrated the best combination of i nsect efficacy and safening toward trout. Significantly different in v ivo efficacies of the N-methyl and N-CD3 analogs suggest that 7 and 8 are proinsecticides requiring activation by dealkylation.