Study On The Synthesis Process Of 4,6-Dichloropyrimidine

The special structures of pyrimidines make their properties unique,especially they have a wide range of pharmacological effects,such as antifungal and promoting plant regulation.Pyrimidines are used as intermediates not only in the synthesis of anticancer,anti-AIDS,antitumor and other drugs,but also in that of pharmaceutical and chemical products including pesticides,herbicides and bactericides.Among them,4,6-dihydroxypyrimidine(DHP)and 4,6-dichloropyrimidine(DCP)are used as intermediates for many common drugs such as adenine and sulfonamide derivatives.It is of great value to investigate the optimization of synthetic conditions.In view of the low yield of DHP and the complicated wastewater treatment in the present synthesis process,it is studied by single factor and orthogonal experiments.Propylene glycol[CH2(COOCH3)2]is reacted with formamide(HCONH2),using sodium methoxide(CH3ONa)as the proper catalyst to synthesize DHP.The optimal experimental conditions are:n[CH2(COOCH3)2]:n(HCONH2):n(CH3ONa)=1:4:4,the reaction time and temperature are 2 h and 60 ~oC,respectively,the yield of DHP can reach as high as 90.4%.Using sulfuric acid(H2SO4)to acidify the sodium salt of DHP can separate sodium sulfate(Na2SO4)and sodium formate(HCOONa)from the wastewater,which realizes the recycling of wastewater and the reduction of production costs.In the synthesis of DCP,an appropriate amount of organic amine as acid binding agent is added dropwise to significantly increase the yield.Therefore,the influence of various factors on the yield in the presence of acid binding agent is investigated through single factor and orthogonal experiments.The optimal conditions for the synthesis of DCP are explored as:n(DHP):n(POCl3):n(5-ethyl-2-methylpyridine)=1:2.2:1.8,1,2-dichloroethane as solvent,the reaction time and temperature are 2 h and 60 ~oC,respectively,the yield of DCP can be up to 94.5%.Finally,the chlorinated wastewater is neutralized by calcium hydroxide[Ca(OH)2],and the high-purity acid binding agent is recovered by azeotropic distillation,and then the separation of calcium phosphate and calcium chloride is realized.By optimizing the reaction conditions,the yield and purity of both DHP and DCP are improved,and the content is identified by thin-layer chromatography.The technology conditions realize the recycling of the acid binding agent and solvent,reduce the amount of raw materials and the cost of three wastes treatment.Thus,the green production of DCP is realized and the economic and environmental benefits are improved.