The Study On Synthesis Of Pyridazine And 4-methyl-Pyridazine

Based on the review of the development of pyridazine compounds (which were useful organic intermediates) and the introduction of the commercialized pyridazine compounds, the general synthesis processes of pyridazine and 4-methyl-pyridazine have been summarized in the thesis.By analysis of the synthesis processes of pyridazine and 4-methyl-pyridazine,the process with maleic anhydride and 3-methylmaleic anhydride as a start material was determined. Through a series of reaction, such as cyclization with a mineral acid salt of hydrazine (hydrazine hydrochloride), chlorination with phosphorus oxychloride, and hydrogenation with Pd/C catalyst. The feasible conditions of above synthetic process were also discussed. The improvements in this research for synthesized process of pyridazine and 4-methyl-pyridazine were listed as follows:(1) Hydrochloride hydrate was replaced by a mineral acid salt of hydrazine hydrochloride in the cyclization. The optimum molar ratio of maleic anhydride(methyl maleic anhydride), hydrochloride hydrate and hydrochloric acid, the optimum reaction temperature and time were determined via a series of parallel experiments. The yields of this step were 95.2% and 96.4%.(2) In the step of chlorination, the optimum molar ratio of maleic hydrazide(methyl maleic hydrazide) and phosphorus oxychloride, the optimum reaction temperature and time were determined via a series of parallel experiments. The yields of this step were 87% and 86.6%.(3) Hydrogenation of 3,6-dichloropyridazine and 3,6-dichloro-4-methylpyridazine with Pd/C catalyst in the presence of triethylamine resulted yields of 85.6% and 83.8%. The optimum molar ratio, reaction temperature and pressure were also determined.The products pyridazine and 4-methyl-pyridazine were obtained by overall yields of 70.9% and 70.0% in this route, and the finally products were identified by melting point test, ~1H NMR and GC/MS. This route is much of industrial value because of the cheap and easily gained materials, the moderate reaction condition, and the convenient operation.