Research On Reaction Of Dichloromethane With Sulfur-nucleophilic Reagents And Pd-catalyzed Demethylation Of Tertiary Amine

In this thesis, synthetic process of 2-(thio-cyanomethylthio)benzothiazole(TCMTB) and demethylation acetylation of N-methyl tertiary amine by Pd-Co synergetic catalysis were studied.1. Optimization of TCMTB synthetic processTCMTB is a kind of broad-spectrum fungicide, which was widely used in industrial and agricultural production. With the expansion of TCMTB application, there are increasing demands for TCMTB. However, high production costs have limited the common use of TCMTB. Therefore, research on optimization of synthetic process of TCMTB is of great significance.In industrial production, dichloromethane acts generally as a reaction solvent. While, reported reactions with dichloromethane as reactant remain relatively rare. It can’t be ignored that dichloromethane can react with nucleophilic reagents to obtain methyl chloride products. In this paper, TCMTB was prepared by two-step substitution reactions with dichloromethane and mercaptan nucleophilic reagent 2-mercaptobenzothiazole as starting materials. A low cost and high yield of TCMTB synthetic route was developed after optimization. In the first step of substitution reaction, bromochloromethane was replaced with dichloromethane as chloromethylation reagent, which reduced the cost of the reaction. The application of triethylamine also increased nucleophilicity of 2-mercaptobenzothiazole. The reaction was conducted under high temperature and high pressure, which improved the selectivity of the reaction and shorten the reaction time. The influences of triethylamine amount, reaction temperature and reaction time on the yield of intermediates were investigated by orthogonal test. In the optimized process, the yield and purity of the product was 89% and 98%, respectively. In the second step of substitution reaction, the reaction was under mixed solvent of chloroform and water, rather than a single solvent system, which reduced the reaction time and difficulty of post reaction treatment. Benzyl triethyl ammonium chloride was used as phase transfer catalyst, which increased the reaction rate. In addition, the influences of catalyst amount, ammonium thiocyanate amount and reaction temperature on the yield of the product was investigated. In the optimized process, the yield and purity of the product reached 95% and 97%, respectively.2. Demethylation acetylation of methyl tertiary amine by Pd-Co synergetic catalysisTertiary amide compound is one kind of important compounds, which has broad applications in functional materials, pesticides, medicine and other fields. Methyl tertiary amines are widely exists in natural product. Of which tertiary amides could be synthesized via demethylation acylation from natural products and drug intermediates containing N-methyl tertiary amine segments, which have very high application values in modification of natural products and drug synthesis of drugs. Transition metal-catalyzed reaction has a very broad application in organic synthesis, while researches on transition metal-catalyzed demethylation acetylation of methyl tertiary amine remain rare.In this paper, demethylation acetylation reaction of N-methyl tertiary amine was studied with precious metal as catalysts and transition metal as synergistic catalysts, then a highly efficient, mild and environment friendly synthetic method was developed. In this paper, different catalysts, reaction atmosphere, reaction solvents, reaction temperature and different cooperating catalyst were optimized. After optimization, palladium acetate was chosen as catalyst, cobalt acetate tetrahydrate was chosen as a synergistic catalyst, oxygen as oxidant, acetic anhydride as the solvent and source of acetyl. This method realized the synthesis of tertiary amides by demethylation acetylation of N-methyl tertiary amine. Reaction activities of different methyl tertiary amines in the reaction system were examined. The result demonstrated that all the substrates had good universality.