5-Chloro-2-hydroxynicotinic acid Chemical Properties

Melting point:

260 °C

storage temp. 

Inert atmosphere,Room Temperature

form 

powder to crystal

color 

White to Almost white

CAS DataBase Reference

38076-80-1(CAS DataBase Reference)

Safety Information

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26-36/37/39-37/39-37

HazardClass 

IRRITANT

HS Code 

29333990

MSDS

• Language:English Provider:ALFA

5-Chloro-2-hydroxynicotinic acid Usage And Synthesis

Synthesis Reference(s)

Synthetic Communications, 19, p. 553, 1989 DOI: 10.1080/00397918908050699

Synthesis

The general procedure for synthesizing 5-chloro-2-hydroxynicotinic acid from 2-hydroxynicotinic acid is as follows: Example 7: Synthesis of 5-chloro-2-hydroxy-3-pyridinecarboxylic acid 1. in a jacketed reactor equipped with an external recirculating coolant, a sodium hypochlorite solution was prepared by slowly adding 35.41 kg (442.6 moles) of a 50% sodium hydroxide solution to 44 kg of flake ice. 2. 61.6 kg of flake ice was then added and 7.87 kg (110.9 moles) of chlorine gas was introduced below the liquid level to ensure homogeneous mixing. 3. 15.0 kg (98% purity, 105.7 moles) of solid 2-hydroxynicotinic acid was added to the above sodium hypochlorite solution in batches. During the addition process, the reaction temperature is increased to 35°C. 4. The coolant in the jacket was removed and the reaction mixture was stirred at room temperature overnight. A sample was taken and acidified with concentrated hydrochloric acid to produce a precipitate. Analysis by 1H-NMR showed that the ratio of 5-chloro-2-hydroxynicotinic acid to unreacted 2-hydroxynicotinic acid was 75:25. 5. A second sodium hypochlorite solution was prepared by adding 10.57 kg of 50% sodium hydroxide solution (132.1 moles), 29.1 kg of ice and 3.65 kg (51.5 moles) of chlorine to the reaction mixture and continued stirring overnight. The sample was again taken and acidified with concentrated hydrochloric acid and 1H-NMR analysis showed no unreacted 2-hydroxynicotinic acid present. 6. 208 g (2.0 mol) of sodium bisulfite was added to decompose the excess sodium hypochlorite. Subsequently 7 L of isopropanol was added to reduce foaming in subsequent steps. 7. The reaction mixture was slowly added to 41.48 kg (34.9 L, 419.3 moles) of concentrated hydrochloric acid under external cooling conditions, keeping the reaction temperature between 15°C and 25°C and the pH of the final mixture at 1.0. 8. The reaction slurry was filtered and the filter cake was washed sequentially with about 20 L of water and 7 L of acetone. 9. The resulting crystals were dried at 100°F to a moisture content of about 5%, then ground and further dried at 120°F to a moisture content of 0.4%. 10. 17.42 kg of product was finally obtained in 95.6% yield. Trace amounts of 3,5-dichloro-2-hydroxypyridine were detected by 1H-NMR analysis as described in Example 3.

References

[1] Patent: US4960896, 1990, A
[2] Synthetic Communications, 1989, vol. 19, # 3and4, p. 553 - 560
[3] Patent: WO2005/21546, 2005, A1. Location in patent: Page/Page column 121; 186-187
[4] Journal of Medicinal Chemistry, 1993, vol. 36, # 18, p. 2676 - 2688
[5] Patent: US4960896, 1990, A

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