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Substituted pyridine carboxylic acid derivatives having pharmacological activity , but also a variety of important and indispensable raw material in the production of pharmaceutical products , pesticides , dyes , surfactants , additives , etc. , can be used as a wide range of uses . Study on the synthesis of substituted pyridine carboxylic acid derivatives is of great significance for the development of new drugs and drug structure transformation . Reading a lot of literature , previous studies based on the synthesis of a series of substituted pyridine carboxylic acid derivatives : (1) 2 - methyl pyridine , 3 - methylpyridine as raw material , hydrogen peroxide oxidation of methyl pyridine nitrogen oxides, by nitration, reduction , diazotization , bromination, cyano , cyano hydrolysis , respectively, 2 - methyl- isonicotinic acid yield of 30.4% , 3 - methyl - isonicotinic acid , to close rate of 13.1% . The method uses potassium ferrocyanide cyano reagents , readily available raw materials , low toxicity , mild reaction conditions . ( 2 ) reported in the literature to 2,3 - lutidine , 2,4 - lutidine, 2 - methyl-5 - ethyl pyridine as the raw material , the selective oxidation of the methyl pyridine carboxylic acid method potassium permanganate oxidation method , this method of production is low , the amount of potassium permanganate , the amount of byproducts is not easy to deal with . This paper proposes a new synthetic route to 2,3 - lutidine , 2,4 - lutidine, 2 - methyl-5 - ethyl pyridine as the raw material , the hydrogen peroxide oxidation of alkyl pyridinium nitrogen oxide , selective oxidation of different concentrations of nitric acid , phosphorus trichloride deoxy Acylation reaction, the esterification reaction step , respectively, to give 2 - methyl- isonicotinic acid oxides of nitrogen , oxides of nitrogen for 2 - methyl- nicotinic acid , 6 - A group - niacin nitrogen oxides, 2 - methyl - isonicotinic acid , 2 - methyl nicotinic acid , 6 - methyl nicotinic acid , 2 - methyl - isonicotinic acid methyl ester nitrogen oxides , 2 - methyl - isonicotinic acid methyl eight pyridine carboxylic acid derivatives. System of Comparative Experiment , discuss the impact of nitric acid concentration on the reaction , to obtain the optimal reaction conditions , the continuous improvement of the treatment after the reaction , initially explored obtained to produce 2 - methyl- nicotinic acid nitrogen oxides , 2 - methyl- isonicotinic acid nitrogen oxides, 6 - methyl- nicotinic acid nitrogen oxides in the best condition. Dialkylamino pyridine as the raw material, the the nitrate selective oxidation of substituted pyridine carboxylic acid has better selectivity , byproducts of nitrogen dioxide gas , may receive recycling , easy to operate , etc. , in particular for the 2 - methyl isobutyl nicotinic acid preparation, high yield , and has good prospects for industrial applications .
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