Hydrochloric Acid → 3-(2-Nitro-5-chlorothiophenoxy)isonicotinic acid

Participants

Reaction Conditions

Reaction Steps

A solution of 3-amino-4-carboxypyridine (1.4 g), sodium nitrite (0.81 g) and aqueous sodium hydroxide 2.9 M (13.3 ml) was added to a solution of aqueous hydrochloric acid 4.3 M (9.8 ml) while the temperature was maintained at 0-5 C. The mixture was stirred for 10 minutes and then added dropwise over the course of 2 hrs to a stirred mixture of 5-chloro-2-nitrothiophenol (2.34 g) and sodium hydroxide (2.63 g) in water (21 ml) maintained at about 53° C. (a brisk nitrogen evolution occurred). The mixture was stirred for 15 minutes, cooled to room temperature and filtered. The fitrate was made strongly acidic (pH=2) with hydrochloric acid 12 M and the precipitated solid was collected by filtration and dried to yield a brownish-orange solid (3 g). The solid was washed with dichloromethane:acetonitrile (30 ml) and dried to leave crude product (1.2 g). Crystallization from ethyl cellosolve led to the pure product, m.p. 280-281, °C.

Provenance & Evidence