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

<p>A regioselective <i>N3</i>-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 (<b>3b</b>–<b>3h</b>). 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 <i>N1,N3</i>-dialkylated derivatives of 2-thiophenytoin in good yields (<b>4b</b>–<b>4g</b>). We were unable to selectively <i>N3</i>-alkylate 2-thiophenytoin with ethyl acrylate at both room temperature and 70°C under the same conditions (<b>4a</b>). Dimethyl and diethyl fumarates cannot work as Michael acceptors and were hydrolyzed to fumaric acid under reaction conditions.</p

Tetrabutylammonium Bromide Media Aza-Michael Addition of 1,2,3,6-Tetrahydrophthalimide to Symmetrical Fumaric Esters and Acrylic Esters under Solvent-Free Conditions

The aza-Michael addition of 1,2,3,6-tetrahydrophthalimide with symmetrical fumaric esters has been performed efficiently in a solvent-free system at 100 °C and using 1,4-diazabicyclo[2.2.2]octane (DABCO) as a base in the presence of tetrabutylammonium bromide (TBAB). The products were obtained in good to high yields within 2.5-7.0 h. This reaction worked well on linear alkyl fumarates and was not effective with nonlinear alkyl fumarates. Although the reaction was also applicable to acrylates such as n-butyl acrylate, methacrylates and crotonates were not suitable Michael acceptors for this reaction