Simplified Procedure for General Synthesis of Monosubstituted Piperazines—From a Batch Reaction Vessel to a Flow (Microwave) Reactor

Abstract

We reported a novel simplified synthetic procedure for the preparation of monosubstituted piperazine derivatives which can now be easily prepared in a one-pot-one-step way from a protonated piperazine with no need of introduction of a protecting group. Reactions, proceeding either at room or higher temperatures in common solvents, involve heterogeneous catalysis by metal ions supported on commercial polymeric resins. A general synthetic scheme was successfully applied to afford a wide range of monosubstituted piperazines. Furthermore, we picked up a set of piperazine derivatives and studied the possibilities of microwave acceleration of given synthetic reactions to make them even more efficient. Our research proceeded from a simple batch technique to the construction of a flow microwave reactor prototype and resulted in promising findings which are summarized and discussed in the article.

Unification of Ullmann and Kharasch coupling: acid promoted CuI catalysed C–N coupling protocols under ligand, base and solvent free conditions

“…We are still unable to perceive the reason for the unusual reactivity pattern of piperazine but we believe piperazine possess a strong basic nature compared to other aliphatic amines. 27–29…”

“…We are still unable to perceive the reason for the unusual reactivity pattern of piperazine but we believe piperazine possess a strong basic nature compared to other aliphatic amines. [27][28][29] Further, the scope of arylhalide with acyclicamines was examined, as summarized in Fig. 5.…”

“…5. Arylchloride bearing an electron withdrawing group reacted efficiently with propylamine (24)(25), diethyl amine (27)(28) and N-ethylpropan-1amine ( 29). The electron withdrawing group at ortho position of arylchloride also reacted well with propylamine (26).…”