2-Chloro Nicotinic Acid

Preparation

Chloronicotinic acid was synthesized from nicotinic acid by oxidation by H2O2 and then chlorinationby POCl3 and PCl5 in a yield of 87.5%.Synthesis of 2-chloronicotinic acid: Pour chlorine gas into the mixed solution of phosphorus oxychloride and phosphorus trichloride, control the temperature at about 60°C, until the remaining chlorine gas escapes, cool and add nicotinic acid N-oxide in batches, and heat the mixed solution. The reaction was carried out at 100-105°C for 1-1.5 h, and the reaction mixture was stirred for 30 min after the reaction mixture was transparent, and phosphorus oxychloride was removed under reduced pressure. The obtained residue was cooled to room temperature, and water was added to obtain the finished product of 2-chloronicotinic acid.

Used in Agrochemical Industries

2-Chloronicotinic acid finds extensive application in the agrochemical industries. It serves as a crucial intermediate for the synthesis of various herbicides and pharmaceutical drugs due to its versatility and importance as a building block. In agrochemicals, it contributes to the production of potent herbicides like diflufenican and nicosulfuron, known for their high biological activities, low toxicity, and broad spectrum.

Used in Pharmaceutical Industries

It is utilized in the synthesis of drugs such as nevirapine, mirtazapine, pranoprofen, and 2-aminonicotinic acids, highlighting its significance in medicinal chemistry.

Methods of production

The synthesis of 2-chloronicotinic acid involves several process routes, including methods using nicotinic acid nitrogen oxide, cyano-containing compounds, or 2-chloro-3-methyl-pyridine as raw materials, with the linear cyclization route being considered highly efficient due to its simplicity, minimal waste generation, and high yield.
Biocatalysis, particularly enzymatic reactions, offers an alternative and environmentally friendly approach for the synthesis of 2-chloronicotinic acid. Enzymes such as amidases play a significant role in catalyzing the hydrolysis of 2-chloronicotinamide to produce 2-chloronicotinic acid. Despite challenges in finding ideal catalysts, efforts in protein engineering aim to improve the catalytic properties of enzymes for efficient industrial production of 2-chloronicotinic acid through biocatalytic routes.

Application

2-Chloronicotinic acid is used in the synthesis of the anti-inflammatory and analgesic pralofen. It is an intermediate of the herbicides nicosulfuron and diflufenican. It is also used as pharmaceutical intermediates for the manufacture of mefenamic acid, niflumic acid, etc.

Consumer Uses

ECHA has no public registered data indicating whether or in which chemical products the substance might be used. ECHA has no public registered data on the routes by which this substance is most likely to be released to the environment.