Study On The Construction Of Thiocarbonyl Compounds Through Inorganic Sulfur Source

Thiocarbonyls as prevalent organic motifs widely exist in the drugs, pesticides, natural products and catalysts, such as Mercaptopurine, Diafenthiuron, Brassinin, and chiral thiourea catalysts, etc. Meanwhile, as significant building blocks, they are widely applied to construction of many important sulfur-containing heterocycles, such as thiazoles, thiazines, thiazolins, and thiazolinones, etc.Conventionally, Lawesson’s reagent and its analogues are applied to transform carbonyl to thiocarbonyl through the replacement of oxygen atom by a sulfur one. But Lawesson’s reagent shows the shortages such as smelly, unstable, higher cost and lower atom economy, which is not conductive to lage-scale prepration. Therefore, the establishment of an effective, practical and green strategy for the construction of thiocarbonyls remains highly desirable. Based on the development of organosulfur chemistry involved green, stable and cheap inorganic sulfur source in our group, we use the strategy of sulfur atom transfer reactions and choose the sodium sulfide and elemental sulfur as sulfur sources to build thiocarbonyl compounds. There are two corresponding parts including in this thesis.Part Ⅰ:Aqueous compatible protocol to thioamide synthesis through sodium sulfide as sulfur sourceWe have developed an efficient aqueous method for the synthesis of thioamides involving aldehydes, sodium sulfide, and N-substituted formamides. Both alkyl and aryl aldehydes were amenable to this protocol with great functional groups toleration. N-substituted formamides were superior to corresponding amines. The method used cheap and readily available sodium sulfide as sulfur source, water as solvent, which made it more efficient and practical. The control experiments showed that imine was a key intermediate for affording the thioamide, and sodium sulfide acted as sulfur source and base in the system. Furthermore, the late-stage modification of natural chiral aldehydes and bioactive molecules derivatives has been established through this protocol.Part Ⅱ:Efficient thiocarbonyl heterocycle construction through elemental sulfur as sulfur sourceWe have achieved an efficient synthetic protocol for the synthesis of thiocarbonyl heterocycles through elemental sulfur and chloroform. Five- to seven-membered thiocarbonyl-containing heterocycles were achieved, such as oxazolidine-2-thiones, thioureas, and thionocarbamates, etc. The control experiments showed that dicholorocarbene was generated from chloroform and afforded the isocycan. The isothiocyanate was then generated from isocycan and elemental sulfur in the basic conditions, which could afford the product by intramolecular nucleophile reaction. So the isocycan and isothiocyanate were the intermediates in the reaction. The protocol avoided the infectant thiophosgene and carbon disulfide and showed the wide substrate compatibility and mild conditions, which conformed to the concept of green chemistry.