Method for preparing 2-chloronicotinic acid

Abstract

The invention discloses a green and environment-friendly method for preparing 2-chloronicotinic acid. The implementation process of the method comprises the following steps: generating aldehyde sodium ethenolate by taking acetaldehyde, sodium methylate and methyl formate as raw materials; reacting with methyl alcohol to generate 1,1-dimethoxy propionaldehyde; reacting with malononitrile to generate a cyclization precursor; and carrying out cyclization, chlorination and cyan-hydrolysis to generate the 2-chloronicotinic acid. The method provided by the invention is novel in line, mild in reaction condition of each step, relatively high in yield, less in generated wastewater and beneficial for reducing the production cost of the 2-chloronicotinic acid, and has industrialization condition. By selecting industrialization products such as the acetaldehyde, the sodium methylate and the methyl formate as raw materials which are easy to get, low in cost, mild and efficient in reaction condition, green and environment-friendly, the invention provides a new way which is novel and efficient and can be used for industrially producing the 2-chloronicotinic acid.

Description

technical field [0001] The invention belongs to the field of organic chemistry, and in particular relates to a method for preparing 2-chloronicotinic acid. Background technique [0002] 2-Chloronicotinic acid, also known as 2-chloronicotinic acid, is a key pharmaceutical intermediate for the synthesis of the anti-AIDS drug nevirapine. It is widely used in the synthesis and research and development of medicines, pesticides, and veterinary drugs, and has high application value and market value. [0003] At present, there are few literature reports on the method of synthesizing 2-chloronicotinic acid in China, and there are mainly four synthetic routes: (1) use nicotinic acid as raw material to prepare nicotinic acid-N-oxide, and then combine the oxide with POCl 3 Chlorination reaction prepares 2-chloronicotinic acid, and this method has low yield due to the low selectivity of 2-position chlorination (Hiroshi Yamanaka.Site-selectivity in the Reaction of Pyridine 1-Oxides with P...

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Problems solved by technology

[0003] At present, there are few literature reports on the method of synthesizing 2-chloronicotinic acid in China, and there are mainly four synthetic routes: (1) use nicotinic acid as raw material to prepare nicotinic acid-N-oxide, and then combine the oxide with POCl 3 Chlorination reaction prepares 2-chloronicotinic acid, and this method has low yield due to the low selectivity of 2-position chlorination (Hiroshi Yamanaka.Site-selectivity in the Reaction of Pyridine 1-Oxides with Phosphoryl Chloride); (2) with 2-Chloro-3-cyanopyridine is used as raw material to synthesize 2-chloronicotinic acid. The raw material of this method is difficult to obtain, so the possibility of industrialization is low (Delarge and C.L.Lapiere. Pyridinecar-boxysulfonic and Pyridine disulfonic Acid); (3) with 2-Chloro-3-methylpyridine is used as a raw material, and the 3-methyl group is oxidized to carboxyl by mixed acid oxidation. This method requires harsh conditions, equipment investment is large, and waste water is produced. It is difficult to industrialized production (J.Cano mondejar, Juan Ferre, Gerardo.Span ES[P]:5011982); (4) Synthesize 2-chloronicotinic acid with 2-chloroaneonicotinoid as raw material. This method is not only difficult to obtain raw materials, but also immature process, basically does not have the conditions for industrialization (M.I.Kabachnik, M.M.Katanelson.Structure of the Isomeric Chloro-anabasine[J].Ber,1935,(68):399-402)

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