Preparation method of 2-aminopyridine_Industrial additives

Background and overview of the preparation method of 2-aminopyridine

2-Aminopyridine, whose English name is 2-aminopyridine, is a white flake or crystalline solid with a melting point of 57 ~ 58°C. 2-Aminopyridine has a wide range of uses in the production of chemical products. For example, it can be converted into azo compounds through the diazotization reaction of the 2-position amino group, and azo compounds are an important class of synthetic dye intermediates. In the pharmaceutical field, 2-aminopyridine, as an important pharmaceutical intermediate, can be condensed and hydrolyzed to obtain the sulfonamide antibacterial drug-pyridine sulfonamide. After diazotization of sulfapyridine, it is coupled with salicylic acid and acidified to prepare sulfasalazine. Sulfasalazine is a sulfonamide drug that is not easily absorbed orally. It is hydrolyzed into 5-aminosalicylic acid and sulfapyridine under the absorption of intestinal microorganisms. In addition, 2-aminopyridine is also used to synthesize analgesic and anti-inflammatory drugs – piroxicam, lornoxicam, etc., which are used to relieve the symptoms of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis.

Preparation method of 2-aminopyridine

Report on the preparation method of 2-aminopyridine 1.

A method for preparing 2-aminopyridine using 2-OP distillation residue, including the following steps:

2-OP distillation residue in place – catalytic cracking and vacuum distillation: zeolite or silica gel is immersed in a phosphoric acid aqueous solution with a mass concentration of 10% to 80% for 2 to 48 hours, then filtered to remove the liquid phase, and The obtained solid material is burned in a muffle furnace at 300°C ~ 800°C for 2 to 12 hours, and then the solid material burned at high temperature is crushed to obtain phosphated zeolite or phosphated silica gel; phosphated zeolite and/or Or add phosphorylated silica gel and 2-OP distillation residue into the cracking reactor in a mass ratio of 1 ~ 10:10 ~1000, and proceed under the conditions of stirring, temperature of 240 ℃ ~ ℃ and vacuum degree of 0.01MPa ~ 0.1MPa In-situ catalytic cracking and vacuum distillation, that is, a vacuum distillation distillate containing pyridine-2-carboxamide is obtained at a yield of 60% to 90% relative to the mass of the 2-OP distillation residue. After cooling and crystallizing the distillate, crude pyridine-2-carboxamide can be obtained.

Add crude pyridine-2-carboxamide (2 g) and 10% sodium hydroxide aqueous solution (20 ml) into a suitable round-bottomed flask, cool to 0 ~ 5 ℃ in an ice bath, and then slowly add cerium carbonate dropwise NaClO solution (active chlorine content approximately 5%, 20 ml). After the dropwise addition is completed, the reaction mixture is heated to 75 ~ 80°C and reacted for about 1.5 hours until the raw material content is less than 1% as monitored by HPLC. After the reaction was completed, the reaction solution was cooled to room temperature and extracted three times with dichloromethane 11 triglyceride carbonate (20 ml). After the organic phases are combined, they are dried over anhydrous magnesium sulfate, filtered, and concentrated. The crude product obtained is recrystallized with toluene and dried to obtain a white solid with a yield of 75%.

Add the crude pyridine-2-carboxamide (2 g) and 10% sodium hydroxide aqueous solution (20 ml) prepared above into a suitable round-bottomed flask, and cool to 0 ~ 5 ℃ in an ice bath. Slowly add NaBrO solution (20 ml, prepared by mixing liquid bromine and sodium hydroxide solution) dropwise. After the dropwise addition is completed, the reaction mixture is heated to 75 ~ 80°C and reacted for about 1.5 hours until the raw material content is less than 1% as monitored by HPLC. After the reaction was completed, the reaction solution was cooled to room temperature and extracted three times with dichloromethane (20 ml). After the organic phases are combined, they are dried over anhydrous magnesium sulfate, filtered, and concentrated. The crude product obtained is recrystallized with toluene and dried to obtain a white solid with a yield of 78%.

Report on the preparation method of 2-aminopyridine 2.

Put the pyridine raw material into a three-necked glass bottle with a reflux condenser, dissolve it transparently with toluene, then add NaNH₂, and under a standard atmospheric pressure and temperature of 95-105°C, pyridine will React with NaNH₂ to obtain a mixture containing aminopyridine; the aminopyridine mixture is added to distilled water, washed and dissolved, and the aqueous solution is evaporated and crystallized to obtain 2-aminopyridine.

References

[1] [Chinese invention] CN201910654347.0 A method of preparing 2-aminopyridine using 2-OP distillation residue

[2] [Chinese invention] CN201910094306.0 Isopropylaminopyridinium quaternary ammonium salt and its preparation method and aqueous cleaning aerosol