Study On Synthesis Process Of Levonorgestrel

Levonorgestrel is the most widely used contraceptives at home and abroad.It is a short-lasting and long-lasting oral contraceptive by inhibition of ovulation.Levonorgestrel is mainly used as visiting pills and emergency contraceptives combined with estrogen.Furthermore,it can also be used to treat irregular menstruation,functional uterine bleeding and endometriosis.The prevailing price of active pharmaceutical ingredient of Levonorgestrel remains high,because current industrial synthetic process route is not environmental-friendly,unsafe,and uneconomical.In this paper,a novel method for synthesis of Levonorgestrel is explored.It adopts the silica-supported sodium-potassium alloy replaces the BIRCH reaction of lithium/liquid ammonia in the original process,breaking through the key technology of chemical synthesis of Levonorgestrel.Compared with the industrial synthetic route adopted by current medical enterprises,this method is safer,more economical and more environmental-friendly.Firstly,this paper studied the feasibility of the synthesis route of BIRCH reaction using silica gel loaded sodium-potassium alloy instead of lithium/liquid ammonia in the original process,and carried out c-nmr,proton NMR,mass spectrometry and other pop analysis with levonorgesterone standard samples to confirm that the chemical structure was correct and the quality was basically consistent.Secondly,this paper studied the influence of two kinds of silica gel loaded sodium-potassium alloys with different molar ratios on the purity and yield of the reaction products,and determined the optimal experimental synthesis conditions by controlling the only variable.The final molar yield was 21%.The results show that the yield of the target product is the highest when the mass ratio of the reaction substrate to the catalytic alloy is 1:7,and the yield is basically stable when the mass ratio of the reaction substrate to the catalytic alloy increases.The research results of this paper have important theoretical and practical significance for the industrial design of Levonorgestrel.