There are various methods of synthesis of 2-chloronicotinic acid at home and abroad。 These include the following nine: 

（1）Nicotinic acid nitric oxide hydrolysis method 

A synthetic method based on nicotinic acid。 This route is the most common process synthesis method, the most mature of the synthesis process, the yield is 45% ~ 50%。 Its advantage for niacin easy, simple process, but the yield is very low, moreover, niacin is also feed and food additives, synthetic product price high, economic benefit is poor。 And prone to 2, 6 - on chloride is replaced, its isomer difficult separation, purity of the product are not up to the standard of the pharmaceutical synthesis, the method in the case of not enough improvement will gradually be eliminated。 

（2）Cyanyl acetate chlorinated - Michael added to ring hydrolysis 

The synthesis method is first after a cyano acetic ester chloride, then through redistribution, synthesis of 2 - chloro - 2 - cyanide - 5 - oxygen pentanoic acid ethyl ester, the synthesis of 2 - ethyl chloride niacin after Michael addition, finally via hydrolysis to 2 - chloro niacin。 The process route is multifarious, and chlorine cyano acetic ester and acrolein are under the environment of strong base to reaction, but also because of its irritating and toxicity of acrolein, do not accord with the idea of green production, so it remains to be further improve the route。 

（3）3-cypyridine nitro-chlorinated hydrolysis method 

3 - cyanopyridine with hydrogen peroxide in the presence of water as medium, generate 3 - cyanopyridine nitrogen oxide, then with phosphorus oxychloride reflux reaction 2 - chloro - 3 - cyanopyridine, hydrolysis and then heating generate 2 - nicotinic acid chloride。 The process is simple and the raw material is easy。 

（4）2 - chlor-3 pyridine oxidation

2 - chloro - 3 - methyl pyridine with potassium permanganate oxidation, pyridine ring side chain alkylation was oxidized to carboxylic acid potassium, with concentrated hydrochloric acid acidification to the isoelectric point, adjust PH = 1 or 2, white 2 - chlorine nicotinic acid precipitation。 The process is simple, the reaction conditions are mild, the product purity is high, but the yield is too low, and the raw material 2-chloro-3-methyl pyridine is difficult to buy。 Therefore, it is not suitable for large-scale industrial production。 

（5）2-chlor-3-trifluorine methyl pyridine initiation 

Will three fluorine chlorine - 2-3 - methyl pyridine and three mixed reaction of alumina 0。5 h, 2 - chloro - 3 - trichloromethyl pyridine, the product with phosphate responding well under 90 ℃, the hydrolysis, can get a 2 - nicotinic acid chloride。 The process route is simple, easy to operate, but three fluorine chlorine - 2-3 - methyl pyridine is also rare, and there exists the problem of waste acid produced, so it is not suitable for mass production。 

（6）Propionyl alcohol is the starting material method 

Propiolic aldehyde oxidation propiolic alcohol, propiolic aldehyde with N, N - dimethylamine reacts 3 - diamine methyl acrolein, make its reaction with cyano acetic ester, generate 1 - cyano - 4 - dimethylamino - 1 - b carbonyl oxygen - 1, 3 butadiene, and chlorine in the presence of HCl closed-loop generate 2 - nicotinic acid ethyl ester, under the condition of alkaline hydrolysis of 2 - nicotinic acid chloride。 

The reaction route to eliminate produced by chlorination of pyridine ring isomer, high selectivity, can obtain high purity chlorine nicotinic acid, 2 - but propiolic alcohol high toxic and explosive raw materials, its operation is difficult, and propiolic alcohol is expensive, the last generation of dimethylamine is gas, it is difficult to recycle, if you can find the substitute, is favorable for industrialization。 

（7）3-methoxypropenal and methyl acetate or ethyl acetate