Microwave-Enhanced Efficient Regioselective Synthesis of 1,3,4-Trisubstituted 2-Mercaptoimidazoles on a Soluble Support

• Published in: Advanced synthesis & catalysis Vol. 354; no. 1; pp. 187 - 196
• Main Authors: Yellol, Gorakh S., Chou, Cheng-Ting, Chang, Wang-Jin, Maiti, Barnali, Sun, Chung-Ming
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.01.2012; WILEY‐VCH Verlag; Wiley; Wiley-VCH
• Subjects: Chemistry; Chemistry, Applied; Chemistry, Organic; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; mercaptoimidazoles; microwave chemistry; nitrogen heterocycles; Organic chemistry; Physical Sciences; polyethylene glycol; Preparations and properties; Science & Technology; soluble supported synthesis; polyethylene glycol; mercaptoimidazoles; DIVERSITY; soluble supported synthesis; microwave chemistry; nitrogen heterocycles; One pot reaction; Imidazole derivatives; Bromoarene; Nitrogen heterocycle; Microwave; Thioureas; Ethylene oxide polymer; Chirality; Organic isothiocyanate; Bromine Organic compounds; Chemical synthesis; Condensation reaction; Regioselectivity; Polymer; Organic bromine compounds; Ketone; Thione; Aminoacid; Optical activity; Soluble compound
• ISSN: 1615-4150; 1615-4169
• DOI: 10.1002/adsc.201100640

A novel efficient synthetic method for regioselective synthesis of optically active 2‐mercaptoimidazoles with three points of structural diversity was investigated on a polyethylene glycol (PEG) support. The key synthetic steps involve (i) synthesis of thiourea derivatives of polymer‐supported amino acids with isothiocyanates and (ii) one‐pot regioselective condensation of PEG‐linked thiourea with α‐bromo ketones to furnish the 2‐mercaptoimidazole skeleton under microwave conditions. An excellent regioselectivity was observed during this one‐pot condensation reaction which was further supported by NOE studies. In addition to three sets of structural diversity, supplementary chirality at the α‐position of the 2‐mercaptoimidazole skeleton is the key feature of this synthesis. A representative set of 2‐mercaptoimidazoles was efficiently assembled on soluble support utilizing various L‐amino acids, isothiocyanates and α‐bromoaryl ketones with good yields.