Alkylation of 3,5-Dimethylisothiazole. A Regioselective Synthesis of S-Alkyl-3-methylisothiazoles

Abstract

3,5-Dimethylisothiazole reacts sequentially with lithiumdiisopropylamide (molar ratio 1:1) and alkyl halides (in excess) affording 5-alkyl-3-methylisothiazoles in excellent yields. When a two-fold excess of base is used, a mixture of 5-monoalkylated and 3,5-dialkylated products is obtained. Sodium amide was also tried as deprotonating agent, but the yield in final products was lower.