Chemistry of Spontaneous Alkylation of Methimazole with 1,2-Dichloroethane

Spontaneous -alkylation of methimazole () with 1,2-dichloroethane (DCE) into 1,2-bis[(1-methyl-1-imidazole-2-yl)thio]ethane (), that we have described recently, opened the question about its formation pathway(s). Results of the synthetic, NMR spectroscopic, crystallographic and computational studies suggest that, under given conditions, is obtained by direct attack of on the chloroethyl derivative 2-[(chloroethyl)thio]-1-methyl-1-imidazole (), rather than through the isolated stable thiiranium ion isomer, i.e., 7-methyl-2, 3, 7-imidazo[2,1-]thiazol-4-ium chloride (, orthorhombic, space group ), or in analogy with similar reactions, through postulated, but unproven intermediate thiiranium ion . Furthermore, in the reaction with , prefers isomerization to the -chloroethyl derivative, 1-chloroethyl-2,3-dihydro-3-methyl-1-imidazole-2-thione (), rather than alkylation to , while further reacts with to form 3-methyl-1-[(1-methyl-imidazole-2-yl)thioethyl]-1-imidazole-2-thione (, monoclinic, space group 2). Additionally, during the isomerization of , the postulated intermediate thiiranium ion was not detected by chromatographic and spectroscopic methods, nor by trapping with AgBF. However, trapping resulted in the formation of the silver complex of compound , i.e., bis-{2-[(chloroethyl)thio]-1-methyl-1-imidazole}-silver(I)tetrafluoroborate ( monoclinic, space group 2), which cyclized upon heating at 80 °C to 7-methyl-2, 3, 7-imidazo[2,1-]thiazol-4-ium tetrafluoroborate (, monoclinic, space group 2). Finally, we observed thermal isomerization of both and 2,3-dihydro-3-methyl-1-[(1-methyl-1-imidazole-2-yl)thioethyl]-1-imidazole-2-thione (), into 1,2-bis(2,3-dihydro-3-methyl-1-imidazole-2-thione-1-yl)ethane (), which confirmed their structures.