Estudi de la desalquilació de la N,N,N’,N’-tetrametiletilendiamina per reacció amb la 4-cloro-2-(metiltio)pirimidina

Abstract

In previous work developed in the research laboratories of the Inorganic Chemistry area from the Department of Chemistry of Universitat de Girona, it was accidentally observed that N,N,N’,N’-tetramethylethylenediamine (TMEDA) was dealkylated by 4-chloro-2-(methylthio)pyrimidine giving aminopirimidines as products. Given the possible pharmacological importance of these products, new attention was focused on this reaction. This document contains the study of the dealkylation reaction of N,N,N’,N’-tetramethyethylenediamine with 4-chloro-2-(methylthio)pyrimidine (P0) to give mainly three products: N,N-dimethyl-2-(methylthio)pyrimidin-4-amine (P1), N,N,N’-trimethyl-N’-(2-(methylthio)pyrimidin-4-yl)ethane-1,2-diamine (P2) and N,N’-dimethyl-N,N’-bis(2-(methylthio)pyrimidin-4-yl)ethane-1,2-diamine (P3). In almost all cases the major product results to be P2 and, in some occasion, the formation of traces of the hydrogenation product of P0, 2-(methylthio)pyrimidine (P4), and of the decomposition product of the substrate, 2,4-bis(methylthio)pyrimidine (P5), has been observed. The effects of the reaction atmosphere, the solvent and the composition of the palladium catalyst have been studied, observing that in all these cases the effect plays a secondary role. Only the reaction temperature seems to have an important repercussion in the reaction conversion. Two of the reaction products, N,N,N’-trimethyl-N’-(2-(methylthio)pyrimidin-4-yl)ethane-1,2-diamine (P2) and N,N’-dimethyl-N,N’-bis(2-(methylthio)pyrimidin-4-yl)ethane-1,2-diamine (P3), have been synthetized, purified and characterized by nuclear magnetic resonance. Moreover, an intermediate product has been synthetized, N-(2-(dimethylamino)ethyl)-N,N-dimethyl-2-(methylthio)pyrimidin-4-ammonium chloride (P6). The obtaining of this intermediate, N-(2-(dimethylamino)ethyl)-N,N-dimethyl-2-(methylthio)pyrimidin-4-ammonium chloride (P6), along with a preliminary study of the reaction kinetics has led to the proposal of a mechanism for the dealkylation of TMEDA and to explain both the formation of N,N’-dimethyl-N,N’-bis(2-(methylthio)pyrimidine-4-yl)ethane-1,2-diamine (P3) from N,N,N’-trimethyl-N’-(2-(methylthio)pyrimidine-4-yl)ethane-1,2-diamine (P2) and the selectivity showed towards the latter