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

• Published in: RSC advances Vol. 13; no. 46; pp. 32772 - 32777
• Main Authors: Hajizadeh, Fatima, Mojtahedi, Mohammad M, Abaee, M. Saeed
• Format: Journal Article
• Language: English
• Published: Cambridge Royal Society of Chemistry 07-11-2023; The Royal Society of Chemistry
• Subjects: Amines; Bromides; Chemistry; Ethylene; Synthesis
• ISSN: 2046-2069; 2046-2069
• DOI: 10.1039/d3ra06678a

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.
A multicomponent synthesis of piperazines tethered to isothiourea group
via
an ethylene link was developed. Several derivatives of the target products are formed by combination of DABCO, alkyl bromides, secondary amines, and phenylisothiocyanate.