Aerobic Oxidative Substitution For Syntheses Of Catechol Thioethers Catalyzed By GA/Fe₂（SO₄）₃

Polyphenol compounds,especially catechol thioethers,are ubiquitous in nature,have anti-oxidant biological activity,and have medicinal values in protecting the heart,antibacterial,anti-cancer,neuroprotection and anti-diabetic.The synthetic methods of catechol thioethers have been reported,but still have some disadvantages,such as the use of equivalent oxidants,strong oxidants,organic solvents,noble metal catalyst,and the formation of disulfide by-products.Therefore,developing a green,efficient and practicable synthetic method for phenolic thioether compounds is important implications.In this paper,catechol thioethers compounds were synthesized via cross-coupling reaction of catechol and mercaptans by using gallic acid(GA)as organic catalyst and ferric sulfate as co-catalyst in aqueous phase.In this study,oxidative cross-coupling of mercaptobenzothiazole and catechol to form 4-(2-mercaptobenzothiazole)thiobenzene-1,2-diol was used as a template reaction to screen and optimize the dosage and proportion of GA and transition metal salts,oxygen pressure,temperature,reaction time and solvent.Finally,the target product 4-(2-mercaptobenzothiazole)thiobenzene-1,2-diol was synthesized form 0.1 mmol catechol and 0.1 mmol 2-mercaptobenzothiazole under the conditions of 1 mol%GA,1 mol%Fe2(SO4)3,2 mL water,2 mL ethanol,0.3 MPa O2;80℃ for 3 h,with a separation yield of 95%.23 thioethers were synthesized by using optimized reaction conditions,of which 11 were new substances.All of thses compounds had been characterized by 1H NMR,13C NMR,melting point and high-resolution mass spectrometry.The possible reaction mechanism was proposed,and the reaction path was considered to be multi-step tandem reactions including aerobic oxidation,1,4-Michael addition or 1,6-Michael addition,and H+shifts.In conclusion,this paper successfully developed a green,efficient and sustainable method for the synthesis of catechol thioethers.