Synthesis of new compounds by selective oxidation of sulfide group present in tetrahydropyridines

This study explores the oxidation reaction of sulfide groups present in methyl 1-(4-chlorophenyl)-4-((4-chlorophenyl)amino)-2,6-bis(4-(methylthio)phenyl)-1,2,5,6-tetrahydropyridine-3-carboxylate -a tetrahydropyridine (THP)- under green rection conditions: ethanol as solvent, aqueous hydrogen peroxide as oxidant agent, phosphomolybdic acid as redox catalyst in atmospheric pressure.

In order to analyze the selectivity towards the corresponding sulfoxide and sulfone, different temperatures, amounts of oxidizing agent and catalyst were tested. The reaction was monitored by thin layer chromatography, and the obtained product was purified by column chromatography and characterized by melting point and Nuclear Magnetic Resonance.

The started THP was prepared by one-pot multicomponent reaction between methyl acetoacetate, 4-chloroaniline, and 4-methyltiobenzaldehyde -in 1:2:2 molar ratio- in methanol as solvent at reflux. Assisted by phosphomolybdic acid, which acts in this opportunity, as acid catalysts. Phosphomolybdic acid is an Keggin heteropolyacid that can operate as Brønsted acid or redox catalysts under mild conditions, favoring selectivity in the reaction and reducing environmental pollution by not producing large volumes of waste, compared with traditional inorganic acid or oxidant.

The optimum condition -124 mg THP, 0.34 mL H2O2 30 %w/V, 4 mg phosphomolybdic acid, ethanol, 50 ºC, 15 h- was extended to other THP prepared from other alkyl acetoacetates and substituted anilines. To our knowledge, neither the oxidation reaction of sulfur atom in THP, nor the corresponding sulfoxides and sulfones, are reported in the literature.