Synthesis And Application Of 1,3,4-thiadiazole And Its Derivatives

5-Methyl-2-mercapto-1,3,4-thiadiazole or thiadiazole for short is widely used in pharmaceutical synthesis,pesticide production,fine chemical industry and other fields due to its unique chemical structure with both nitrogen and sulfur heteroatoms.The traditional process to manufacture thiadiazole generally generates serious environmental pollution,therefore,it is necessary to develop environmentally friendly technology to produce thiadiazole.Besides,it is also very important to develop downstream products of thiadiazole based on its special structure.Firstly,the synthetic route different from the traditionally domestic process for the manufacture of thiadiazole was determined through consulting literature.First,potassium hydrazine dithioformate(potassium salt for short)as an intermediate is synthesized from the reaction of hydrazine hydrate with carbon disulfide in the presence of KOH.Through a series of experiments,the optimal reaction conditions are determined as follows:the molar ratios of NH₂NH₂·H₂O:KOH:CS₂ of 1:1:1,reaction temperature of-15°C,absolute ethanol as solvent,dropping time of CS₂of 3h,and reaction time of 3 h.Under these conditions,the yield of potassium salt reached up to 99.18%.Then,another intermediate ethyl acetimide hydrochloride(acetamide salt for short)was prepared by reaction of acetonitrile with HCl and ethanol.Through a series of experiments,the optimal reaction conditions are obtained,which are the molar ratios of CH₃CN:HCl:C₂H₅OH of 0.80:1:1.40,reaction temperature of 0?,and reaction time of 53 h.Under these conditions,the yield of acetamide salt was88.57%.Finally,5-methyl-2-mercapto-1,3,4-thiadiazole was synthesized from the above two intermediates in a yield of 92.87%under the optimal conditions which are the reaction molar ratio of potassium salt:acetamide salt of 1:1.05,reaction temperature of 40°C,reaction time of 3h,water as solvent,and the molar ratio of potassium salt to water of 1:27.In addition,based on the above process conditions,a workshop for an annual output of 100tons of thiadiazole was designed.A chiral sulfoxide ligand was synthesized from 5-methyl-2-mercapto-1,3,4-thiadiazole and N-benzyl pyrrolidine diol as starting materias through a series of reactions.The chiral sulfoxide ligand was tested in the rhodium-catalyzed asymmetric 1,4-addition reaction,asymmetric alkyl zinc addition reaction and asymmetric synthesis of cyanohydrin,respectively.Although the products can achieve good yield,but no expected result of chiral induction was received.A palladium complex was prepared from coordination of 5-methyl-2-mercapto-1,3,4-thiadiazole with palladium dichloride to form a palladium complex.The complex was supported on chitosan,which was used as a catalyst precursor.Several nitrogen-sulfur co-doped carbon supported palladium catalysts denoted as Pd-NSC-T were prepared by pyrolysis the precursor at different temperatures.The catalysis of the catalysts Pd-NSC-T were evaluated in the selective semi-hydrogenation of alkynes with hydrogenation of phenylacetylene as a model reaction.The catalyst Pd-NSC-800 obtained at the pyrolysis temperature of 800?showed best catalysis among all the catalysts.The optimal reaction conditions were achieved through a series of experiments,whih were,ethanol as solvent,H₂pressure of 1.00 MPa,catalyst loading of 0.11 mol%,reaction temperature of 25?,and reaction time of 60 min.Under the optimal conditions,the conversion of phenylacetylene reached up to 98.1%,and the selectivity of styrene was as high as 94.8%.Compared with Pd/C,this catalyst showed high chemical selectivity in the reaction.