Organic-salt-mediated highly regioselective N3-alkylation of 2-thiophenytoin via Michael reaction under solvent-free conditions

• Main Authors: Gholamhassan Imanzadeh, Aazam Aliabadi, Mohammadreza Zamanloo
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2016-04-01
• Series: Green Chemistry Letters and Reviews
• Subjects: Solvent-free; regioselective; Michael addition; 2-thiophenytoin; α; β-unsaturated esters
• Online Access: http://dx.doi.org/10.1080/17518253.2016.1177606

A regioselective N3-alkylation of 5,5-diphenyl-2-thiohydantoin (2-thiophenytoin) using a very efficient mild base K2CO3 and α,β-unsaturated esters in the presence of organic salt TBAB (tetrabutylammonium bromide) at room temperature has been reported (3b–3h). The selectivity of this reaction is excellent and products have been produced in good yields under solvent-free conditions. The increase of the reaction temperature to 70°C mostly disappeared this selectivity and afforded only the N1,N3-dialkylated derivatives of 2-thiophenytoin in good yields (4b–4g). We were unable to selectively N3-alkylate 2-thiophenytoin with ethyl acrylate at both room temperature and 70°C under the same conditions (4a). Dimethyl and diethyl fumarates cannot work as Michael acceptors and were hydrolyzed to fumaric acid under reaction conditions.