Ruthenium‐Zeolite Catalyzed Dehydrative N‐Benzylation of Amides for the Construction of Macrolactams Under Continuous Flow

Abstract

Continuous‐flow synthesis of acyclic amides and macrolactams has been demonstrated successfully via N‐benzylation of amides using a highly reusable heterogeneous Ru‐Zeolite as a catalyst, which gives only water as the byproduct. N‐Benzylation of acyclic amides furnished 30 N‐benzylated amides whereas intramolecular N‐benzylation with alcohols was well tolerated with 15 examples of macrolactams bearing 11‐ to 15‐membered rings. Notably, the scalability of this flow process has been demonstrated from milligrams to gram scale using the Ru‐Zeolite heterogeneous catalyst. Moreover, the reusability of the catalyst is exemplified by the 16 reaction cycles carried out with one time‐packed heterogeneous catalyst in the reactor bed.