Condensation of alpha-Chloroethers of Unsaturated C-3-Alcohols with Thioacetamide and Thioureas

摘要

The synthesis of heterocyclic compounds by the Hantzsch reaction is proposed. The synthesis involves the reactions of 1-(chloromethoxy)prop-2-ene and 1-(chloromethoxy)prop-2-yne with thioacetamide, thiourea, and phenylthiourea and results in the preparation in high yields of previously unknown imidothioates, which are promising intermediates. The proposed efficient regioselective synthesis of new types of compounds by the reaction of alpha-chloroaldehydes and ketones with thioamides and thioureas can be used to prepare thiazole derivatives. If the reaction is stopped at the stage of formation of intermediate imidothioates and isothioureas, the product of alkylation of the starting compounds at the sulfur atom can be obtained. The reactions of 1-(chloromethoxy)prop-2-ene and 1-(chloromethoxy)prop-2-yne with thioacetamide, thiourea, and its N-phenyl derivative in methanol at room temperature leads to the formation of the target imidothioates in yields of up to 62.5. A typical reaction with phenylthiourea is performed in dry acetone under reflux for 1 h in the presence of a catalytic amount of MgSO4 with the subsequent alkalization with aqueous NaOH and purification of the target products by column chromatography. The yields of the products depend their structure: the yields of the propargyl derivatives (prop-2-yn-1-yloxy)methyl ethanimidothioate, (prop-2-yn-1-yloxy)methyl carbamimidothioate, and (prop-2-yn-1-yloxy)methyl N-phenylcarbamimidothioate are higher compared to their allyl analogs (prop-2-en-1-yloxy)methyl ethanimidothioate, (prop-2-en-1-yloxy)methyl carbamimidothioate, and (prop-2-en-1-yloxy)methyl N-phenylcarbamimidothioate. The synthesized compounds are hydrolytically stable, have an increased reactivity, and are also rich in nucleophilic centers. The composition and structure of the products were confirmed by elemental analysis and IR and NMR spectroscopy.