Eschenmoser coupling reactions starting from primary thioamides. When do they work and when not?

Abstract

Reactions of thiobenzamide or thioacetamide with 4-bromo-1,1-dimethyl-1,4-dihydroisoquinoline-3(2H)-one, 4-bromoisoquino-line-1,3(2H,4H)-dione and two alpha-bromo(phenyl)acetamides were examined under various conditions (base, solvent, thiophile, tem-perature) and structure/medium features that influence product distribution (Eschenmoser coupling reaction, Hantzsch thiazole syn-thesis and elimination to nitriles) were identified. The key factor that enables the successful Eschenmoser coupling reaction involves the optimum balance in acidity of nitrogen and carbon atoms of the intermediary alpha-thioiminium salts.