Synthetic method of 2-chloronicotinic acid

Abstract

The invention discloses a synthetic method of 2-chloronicotinic acid, and the method comprises the steps of taking niacin N-oxide as shown in formula III and bis(trichloromethyl) carbonate as shown in formula II as raw materials to react under solvent-free conditions and under the action of phase transfer catalyst of quaternary ammonium salt, heating to 100-110DEG C and reacting for 2-10h, and after the reaction is finished, preparing the 2-chloronicotinic acid by separating and purifying the reaction solution, wherein the amount ratio of N-oxide to bis(trichloromethyl) carbonate to quaternary ammonium salt is 1:0.4-0.6:0.1-0.2. The method uses the bis(trichloromethyl) carbonate to replace toxic reagent of phosphorus oxychloride and phosphorus pentachloride, and the obtained product has the advantages of high yield, high purity and the like. The method has advanced process route, mild reaction condition, high reaction yield, less three-wastes, no toxic reagent and larger implement value and social and economic benefits.

Description

(1) Technical field [0001] The invention relates to a chemical synthesis method of 2-chloronicotinic acid, in particular to a chemical synthesis method for preparing 2-chloronicotinic acid by reacting bis(trichloromethyl)carbonate and nicotinic acid N-oxide. (2) Background technology [0002] In recent years, with the development of pesticides and pharmaceutical sciences, niacin series chemicals have received more and more attention and applications. Among them, 2-chloronicotinic acid is used as an agricultural and medical intermediate to prepare the new high-efficiency herbicide Nicosulfuron (Nicosulfuron), the non-steroidal anti-inflammatory analgesic drug Niflumic acid, pranoprofen and HIV reverse transcriptase Inhibitors such as nevira and others are in short supply at home and abroad. Therefore, the research on the preparation of 2-chloronicotinic acid is of great significance. [0003] The main synthetic methods of 2-chloronicotinic acid mainly include: (1) ring form...

AI Technical Summary

Problems solved by technology

[0003] The main synthetic methods of 2-chloronicotinic acid mainly contain: (1) ring-forming method of alkenyl ether or alkenyl amine and ethyl cyanoacetate, the raw materials of this method are more expensive and the generation cost is higher

(2) Ethyl cyanoacetate is chlorinated, added with acrolein Michael, and hydrolyzed after forming a ring. The main raw material of this process, acrolein, is highly irritating and toxic, and there are many types of organic solvents in the production process. , the process is complex and not suitable for mass production

(3) Nicotinic acid synthesizes 2-chloronicotinic acid through hydrogen peroxide nitrogen oxidation, chlorination, and hydrolysis. This method is currently widely used in industrialization, but there are also large amounts of chlorinated reagents such as phosphorus oxychloride and phosphorus pentachloride. Phosphorus-containing wastewater is difficult to treat, and it is easy to cause oxidative enrichment of the environment. The problem of environmental pollution is serious. With the strict implementation of the national environmental protection law, manufacturers using this process face the fate of stopping production or restricting production.

At the same time, the original process also has problems such as low product yield and purity (generating isomer 6-chloronicotinic acid in the reaction process) to be solved

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