Synthesis and structure study of 2-alkenylsulfanyl-1-methylimidazoles

Abstract

Derivatives of 1-methylimidazole-2-thiol (1) bearing substituents of various kinds are prom-ising ligands for modeling various enzymatic systems and structures with pharmacological activity. They are widely used as intermediates in the synthesis of organic compounds possessing biological activity (antitumor, antimicrobial, antidiabetic, antithyroid, antihistamine, antiprotozoal, and antiviral) as well as agrochemicals, dyes, photochemicals, corrosion inhibitors, epoxy hardeners, adhesives, and plastic modifiers. In the present paper we have studied the interaction between 1-methylimidazole-2-thiol 1 and prenyl bromide (2a), trans-cinnamyl chloride (2b), and butenyl bromide under various conditions for the first time. It has been found that selectivity of the alkylation reactions of compound 1 depends on the reaction conditions (alkylating agent, solvent, and base). Synthesis of individual 1-methyl-2-prenylsulfanylimidazole (3a) (yielding 78–86 %), 1-methyl-2-cinnamylsulfanylimidazole (3b) (yielding 94–97 %), and 2-(3-butenyl)sulfanyl-1-methyl-imidazole (4) (yielding 33–75 %) has been carried out by alkylation of 1-methylimidazole-2-thiol 1 with prenyl bromide 2a, trans-cinnamyl chloride 2b, and butenyl bromide, respectively, in the following systems: i-PrOH–i-PrONa, K2CO3–Me2CO (for 3а), MeOH–MeONa, i-PrOH–i PrONa, K2CO3–Me2CO, K2CO3–MeCN and i-PrOH–i-PrOК (for 3b), MeOH–MeONa, i PrOH–i-PrONa, K2CO3–Me2CO, K2CO3–MeCN, i-PrOH–i-PrOК and КОН–H2O–BTEAC (for 4). The structure of the synthesized compounds 3a,b and 4 has been studied and proved by mass spectrometry (GC–MS), as well as ¹H, ¹³C NMR spectroscopy. General predictable directions for fragmentation of the molecular ions of S-derivatives 3a,b and 4, which are accompanied by elimination of methyl/phenyl and thiol radicals, have been revealed. The evidence that alkylation reactions occur at the sulfur atom is the presence of signals for the –SCH2– protons in the region of 3.12–3.84 ppm in the 1Н NMR spectra of compounds 3a,b and 4. According to the 1Н NMR data, it has been found that alkylation of 1-methylmimidazole-2-thiol 1 at other conditions leads to formation of small quantities of by-products, such as N-alkenyl and S,N-dialkenyl derivatives, due to its thione-thiol tautomerism.