A Useful Reagent for the Synthesis of Piperazines

N,N-Bis[2-(p-tolylsulfonyloxy)ethyl]-p-toluenesulfonamide (1) is generally used for the synthesis of azacrown ethers and azamacrocyclic compounds. Recently, Huang and Li et al. have developed the method for the synthesis of piperazine blocks by the reaction of 1 with amines. In this reaction, N-alkyl-N’-tosylpiperazine derivatives are obtained by using aliphatic primary amines. When using aminoalcohols, 1 reacts with only the amino group to afford piperazines having a hydroxyl group at their terminal. Furthermore, the reaction of 1 with diamines or polyamines preferentially affords mono-piperazines with the formation of di-piperazines as minor products. Primary amines preferentially react with 1 compared with secondary amines due to having a higher reaction rate. It is presumed by means of DFT calculations that this reaction proceeds via the 6-membered ring transition state.