Study On The Synthesis Of Three Kinds Of Pyridine Base Derivatives

With the extensive use of pyridine and its derivatives in medicine and pesticide industry, the synthesis of these compounds become the focus of research and development in the Fine Chemical Intermediates preparation and package service. On one hand, the preparation technology of pyridine base and part of its derivatives have been becoming more and more mature and there are exuberant demands of them; on the other hand, these heterocyclic compounds bring out great pressure to the environment.Therefore, in the papers, we aimed to find out a green organic synthesis way for several typical pyridine base derivatives, considering the replacement of raw materials, solvents and reagents, the optimization of reaction processes and atom economy. As a result, we chose 2-chloropyridene as the raw material to synthesis 2-chloro-4-nitro pyridine and 2-chloro-4-aminopyridine, selected sulfuric acid as the catalyzer and 30% hydrogen peroxide as the oxidant instead of 50% hydrogen peroxide, which guaranteed well yields and good stability of the technology. Moreover, the amount of acetic acid, using as the solvent, had been reduced from 10 times equivalent to 3～5 times. In the reduction process, we investigated the effectiveness of Raney Ni and hydrazine hydrate and gained ideal results in small experiments. Then we chose ethyl nicotinate as the raw material to synthesis 3-pyridinioacetate, correcting the conception that using high cost nicotinic acid to synthesis ethyl nicotinate. Our optimized method, which was suitable for scale-up, was much milder in the acidolysis and decarboxylation of ketonic acid ester intermediates, and realized solvent emission reduction through reusing extractants. At last, we chose 2,3,5-trimethylpyridine as the raw materials to synthesis 2-chloro-methyl-3,5-dimethyl-4- methoxylpyridine, chose 2,3-dimethyl pyridine to receive 2-chloromethyl-3-methyl-4-(2,2,2- trifluoroethoxy) -pyridine, and chose furan to gain 2-chloromethyl -3,4-dimethoxylpyridine. In the process, we selected boron trifluoride as the catalyzer in the Friedel-Crafts reaction, optimized the oxidation reaction according to the preparation of 2-chloro-4-nitropyridine, and discussed the mechanism and application of Bockethide reaction and the mechanism and influence factors in the synthesis of pyridine from furan. On the basis of the previous work, we designed synthesis routes for three kinds of prazoles. By small experiments, with certain sacrifice of yield, we had found out the optimum ratio of raw materials, which improved the production efficiency. Besides, we replaced highly toxic raw materials, such as dimethyl sulfate and potassium cyanid and characterized ~1HNMR of relative compounds.