1H NMR kinetic and mechanistic study of the formation of amino acid derived N-allyl-2-thiohydantoins

Abstract

The reaction between amino acid esters and allyl isothiocyanate leading to the formation of N-allyl-2-thiohydantoin derivatives is investigated using 1H NMR spectroscopy. The reactions are carried out at ambient temperature in CDCl3, in the presence of triethylamine as a base, under second-order conditions with an initial molar ratio 1:1. The changes in intensities of relevant signals show that after a few days there is only one dominant product in the system. Monitoring of the formation of thiohydantoin derivatives by 1H NMR spectroscopy confirmed that the reaction occurs in two consecutive steps. The first step is formation of thiohydantoic acid which undergoes cyclization in the second step, forming the thiohydantoin nucleus. The rate constants are calculated after integration of the relevant signals of substrate and product of the cyclization. The reactivities of the amino acid esters are compared and a conclusion is made on the basis of their afinities towards cyclization to thiohydantoins in regards to their structure relationships.