Synthesis Of Disulfides And Sulfides Under Metal-free Catalytic System

Many chemists always pay much attention to organosulfur chemistry,which is an important branch of organic chemistry.Thioether derivatives are indispensable in many important synthetic chemistry,biochemistry and industrial applications.As a result,the development of simply and efficient protocols for the synthesis of Thioether derivatives are very desirable.Oxidative coupling is a class of significant organic reactions in methodology in the past decade.This work focuses on one-step synthesis of various disulfides and 3-sulfenylindoles using oxidative coupling as guiding conception.Part 1.The tert-butyl nitrite?TBN?/O₂ catalytic system was developed in the preparation of disulfides.With thiophenol as the model substrate,the reaction conditions,including the amount of catalysts,the effect of solvents,the reaction temperature and time,were screened.On the basis of these experimental data,we concluded that 4 mol%of TBN in DCE at 50°C was suitable for oxidation of thiols to disulfides under atmospheric pressure of O₂.Under this optimal reaction conditions,phenyl disulfide was isolated in 90%yield.The proposed reaction system was also suitable in the oxidative coupling of a variety of aromatic thiols,heteroaromatic thiols and aliphatic thiols,and a broad range of corresponding disulfides were synthesized in71-97%.Part 2.The I₂/DMSO catalytic system was developed in the preparation of 3-sulfenylindoles.With the cross-coupling of indole and thiophenol to form 3-sulfenylindole as model reaction,the reaction conditions,including the amount of catalysts,the effect of solvents,the reaction temperature and time,were screened.When the ratio of indole and thiophenol was 1:1,the optional reaction was obtained that the reaction was carried out with 5 mol%of I₂ as the catalyst,3 equiv.of DMSO as oxidant and DCE as solvent at 60°C for 6 h.Under this optimal reaction conditions,3-sulfenylindole was isolated in 92%yield.The proposed reaction system was also suitable in the cross-coupling of a variety of indoles and thiols,and corresponding 3-sulfenylindoles were obtained in 74-96%yields.Part 3.The KI/HBr/NaNO₂/O₂ catalytic system was developed in the preparation of 3-sulfenylindoles.With the cross-coupling of indole and 4-chlorothiophenol to form 3-??4-chlorophenyl?thio?-1H-indole as model reaction,the reaction conditions,including the kinds of catalysts,the effect of solvents,the amount of catalysts and the reaction temperature,were screened.When the ratio of indole and 4-chlorothiophenol was 1:1,the optional reaction was obtained that the reaction was carried out with 15mol%of KI as the catalyst,20 mol%of HBr and 15 mol%of NaNO₂ as the co-catalysts,oxygen as oxidant and ethanol as solvent at 60°C for 3 h.Under this optimal reaction conditions,3-??4-chlorophenyl?thio?-1H-indole was isolated in 87%yield.The proposed reaction system was also suitable in the cross-coupling of a variety of indoles and thiols,and corresponding 3-sulfenylindoles were obtained in82-96%yields.In conclusion,compared to the traditional ones,novel routes for the synthesis of disulfides and 3-sulfenylindoles have been proposed from commercial available raw materials.The newly developed protocols were facile,mild and easy to operate.