Syntheses Based on Natural α-Amino Acids. Cyanoethylation of 3-Substituted 5-Methyl-2-thiohydantoins

Abstract

The wide distribution of hydantoins in nature and the presence among them of active regulators of plant growth [1,2] has defined the problem of the present work, viz. the synthesis of analogs of these compounds, substituted 2-thiohydantoins. The closeness of the latter in structure to compounds isolated from a whole family of plant sources [3], guarantees the safety of their practical use, since degrading enzyme systems exist in plants preventing an excessive accumulation of both the natural compounds and their analogs [4].To solve this problem we have studied the cyanoethylation of the known 5-methyl-3-phenyl(allyl)-2thiohydantoins 1a,b obtained previously by the interaction of α-alanine with phenyl and allyl isothiocyanates [5].When using 2-thiohydantoins in synthesis it is necessary to consider the readily occurring isomeric and tautomeric conversions of these molecules. Its thioamide fragment S=C-NH 2 is a tautomeric triad, in which the equilibrium is displaced in the direction of the NH form [6]. The latter circumstance determines the ambiguity of the reactivity of anions of compounds of type 1. Investigations showed that predominantly N-alkyl derivatives are formed on alkylation of 2-thioxoimidazolidines with hard reagents in polar solvents [7,8]. At the same time the predominant formation of S-alkylation products is observed in reactions with soft alkylating agents in solvents of low polarity [9]. In other words, in polar solvents the reaction is directed to the center of basicity, the N atom of the triad [10][11][12]. In nonpolar solvents a determining role is played by the polarizability of the reaction center, which is greater at the sulfur atom than at the nitrogen. It is also known that on alkylation of imidazolidinethiones the alkylation begins at the more nucleophilic sulfur atom [13], but alkylation of N-aminoazolinethiones occurs exclusively at the sulfur atom [14] and in this respect they do not differ from other heterocyclic thiones [15]. In compounds 1a,b there is an additional reaction center at the C (5) atom, at which alkylation may also occur. Because of this there is undoubted interest in clarifying the direction of alkylation of thiohydantoins 1a,b.By cyanoethylating compounds 1a,b with an excess of acrylonitrile in alcohohol in the presence of a catalytic amount of sodium hydroxide at room temperature, a mixture was obtained in both cases consisting mainly of products of C and S alkylation 2a,b to 4a,b (overall yield up to 90%, see Table 1), among which the double alkylation products 3a,b (yields up to 50%) predominated. __________________________________________________________________________________________