An Efficient Conversion of N-Alkyllactams to N-Alkylthiolactams

Abstract

The lactam-to-thiolactam transformation is of considerable utility in the synthesis of natural products.³ We report on a two-step preparative route for the thionation of N-alkyllactams that is (i) superior to that effected by P₄S₁₀ ^4,5 or diethylthiocarbamoyl chloride⁶ (ii) safer and more efficient than the sulfhydrolysis of lactamium salts with H₂S,³ and (iii) cleaner and thermally milder than that accomplished by the use of Lawesson's reagent.⁷ The method is analogous to our lactone-to-thionolactone transformation⁸ and it consists of O-alkylation of the lactam (1) with R₃O^±BF₄ (R=Me, Et),⁹ followed by treatment of the intermediate salt (2) with anhydrous NaSH¹⁰ in acetone at O°C. The following Table shows our results for the synthesis of thiolactams 9–13 when we apply our method (Method A) and those reported previously (Methods B-D).