Mechanically Activated Ring‐Opening Reactions of N‐Acyl‐1,2,3,4‐tetrahydroisoquinolines Derived from the Synthesis of Praziquantel Intermediate.

Abstract An unexpected DDQ-promoted ring-opening reaction of N-chloroacetyl-tetrahydroisoquinoline under ball milling conditions was revealed during the synthesis of Praziquantel. A variety of N-acyl-tetrahydroisoquinolines were then tested to further investigate the reaction, and plausible reaction mechanism was proposed. Ball milling was demonstrated to be an efficient tool to promote this oxidative ring-opening reaction to give products in satisfactory yields with good selectivity in short reaction times.