One-pot four-component synthesis of novel isothiourea-ethylene-tethered-piperazine derivatives

Abstract

An efficient metal-free four-component approach for the synthesis of piperazine derivatives tethered to an isothiourea group through an ethylene link was developed. 1,4-Diazabicyclo[2.2.2]octane (DABCO) salts, generated in situ through the reactions of DABCO with various alkyl bromides, reacted with phenylisothiocyanate (PITC) and amines in a one-pot manner to give the target products. Initially, through two parallel nucleophilic paths, DABCO and the secondary amine adds to the alkyl bromide and PITC, respectively. The process is followed by the combination of the two respective intermediates to produce the final products by forming a new C–S bond with the expense of a C–N bond cleavage. Consequently, various DABCO salts and secondary amines were tolerated well in this protocol to afford the isothiourea-ethylene-tethered-piperazine compounds in good to high yields.