Study On The Synthetic Of Methyly Hydrazine And Its Derivatives

Cephalosporins are the most commonly used for the treatment of bacterial infections diseases, these drugs have a variety of advantages, including wide antimicrobial spectrum,resistances acid and alkali as well as low toxicity. They have been commonly widespread use in clinical medicine. Ceftriaxone is quite important species in third generation semi-synthetic cephalosporin antibiotics which have strong activity for enterobacteriaceae. The drug was actively against the majority of infections caused by aerobic Gram-negative bacteria.Methyl hydrazine and its derivatives 2-methyl-amino-thiourea are an important intermediate in the synthesis of the third-generation cephalosporins——ceftriaxone. Because of ceftriaxone,s huge market demand, which led to the rapid development of ceftriaxone intermediates industry chain. Therefore, exploration and discovery a mature and feasible synthesis process of which can not only great social benefits but also generate considerable economic benefits. Further, methyl hydrazine also has a significant purpose in military industry, because of its low freezing point, high combustion characteristics that can be used as a rocket propellant. Another methyl hydrazine derivatives of 1-methyl-3-propyl-pyrazole-5-carboxylate is an important intermediate which was applied to synthetic famous anti-ED drugs sildenafil(commonly known as "Viagra"). In this paper, based on analysis of existing synthetic route and combined with the current situation, we adopted a synthetic process which is suitable for industrial production as well through control of a single variable and orthogonal experiment process was optimized by the selection of the optimal process conditions,complete the following tasks.Based on reference literature that designed synthesis of monomethyl hydrazine process route, which determined the hydrazine salt as raw material, methanol as methylating agent,and through catalytic by methyl chloride get free methyl hydrazine products. By the orthogonal experiment demonstrated the optimum reaction conditions that the feed ratio of Mhydrazine salt: Mmethanol: Mdichloromethane = 1: 4: 0.1; the reaction temperature was 115 o C; the reaction pressure was 0.55 MPa; the reaction time was 2.5 h. As a prerequisite, to ensure the yield of the reaction, by coordinating the relationship between the reaction temperature and feeding, pressure, the reaction time is shortened and the process become more secure. And thereaction selectivity greater than 99% methylation, methyl hydrazine single molar yield of28.7%, the circulation hydrazine salt of methyl hydrazine overall molar yield greater than84%.2-amino-thiourea was synthesized from methyl hydrazine, obtained by orthogonal experiment get the best reaction process conditions which the molar feed ratio Mmethyl hydrazine:MNH4SCN= 1: 1.1; the reaction time was 2.5 h; the reaction temperature was 100 o C; and innovated catalyst, instead of polyethylene glycol 400 as a reaction catalyst to shorten the reaction time and obtain a regular crystal form and a granular product is higher than 88%product yield, purity higher than 98.5%.About the synthesis of 2,4-dioxo-heptanoic acid ethyl ester which is the intermediates of1- methyl-3-propyl-pyrazole-5-carboxylic acid ethyl ester, The optimum reaction solvent is tetrahydrofuran. Solvent recovery makes it easier to apply and reducing the process costs.About the synthesis of intermediates of 1-methyl-3-propyl-pyrazole-5-carboxylate, Feed ratio was determined through the experiment to Mmethyl hydrazine: M2,4-dioxo heptanoate = 1: 1.1, 40 ~ 50℃as the best reaction temperature, 2.0 h as the optimum reaction time. Get the products yield is greater than 90% and purity greater than 98%.Compared with the traditional production method, the process route in this paper had made development in the process, the raw material cost, the product yield and purity, and the environmental protection.