Synthesis Of 4-(Trifluoromethyl) Nicotinic Acid And Its Derivatives

4-trifluoromethylnicotinic acid and 4-(trifluoromethyl)nicotinamide compounds are important intermediates to produce agricultural chemicals or pharmaceuticals. Some 4-(trifluoromethyl)nicotinamide compounds can be used as active ingredients for pesticides directly. They can kill the pests effectively and protect domestic animals from the harmfulness because unique mechanism and high biologically activity. In addition, they can also solve the hard problem of the resistance of pests to other pesticide. Therefore, it is of great practical value to research on synthesis of 4-trifluoromethylnicotinic acid and its derivatives.Several possible synthesis routes were designed in this dissertation after review the relevant reference. But two methods were eventually designed and explored after taking some factors into consideration such as cost, difficulty of industrial production, reagent characters. The first, Condensation of trifluoroacetoacetate with cyanoacetamide obtained 2,6-dihydroxy-4-(trifluoromethyl)nicotionitrile, and chlorination of above product resulted in 2,6-dichloro-4-(trifluoromethyl)nicotionitrile. Then the above product via hydrolysis, hydrogenolysis,4-trifluoromethylnicotinic acid was obtained. The other, ethyl vinyl ether reacted with trifluoroacetic anhydride to get 4-ethoxy-1,1,1-trifluoro-3-buten-2-one, then 4-trifluoromethylnicotinic acid was prepared via amination, condensation, ring closure and hydrolysis. It was found that the former method had the advantages of a good yield and convenient operations, the latter method had a poor yield and still need modification. 4-(trifluoromethyl)nicotinamide and N-(cyanomethyl)-4-(trifluoromethyl)nicotinamide were also synthesized, which are two important derivatives of 4-trifluoromethylnicotinic acid.Each step of the experiment was optimized so that we can determin the most effective conditions. The product and intermediate of each step were characterized by the melting point determination, MS,1H NMR. The results proved the structures of the products conformed to the target products, which verified two routes of synthesis of 4-trifluoromethylnicotinic acid to be efficient.