Method for preparing isonicotinic acid and pyrazinamide by non-catalytic hydrolyzing isonicotinonitrile in near-critical water medium

Abstract

The invention discloses a method for simultaneously preparing pyrazinamide and isonicotinic acid through uncatalyzed hydrolysis of isonicotinic nitrile in a near critical water medium. The method comprises the following steps: adding deionized water and the isonicotinic nitrile into a high-pressure reaction kettle, stirring the mixture, raising the temperature to the boiling point at normal pressure, and opening an exhaust valve for 2 to 5 minutes; closing the exhaust valve, continuously raising the temperature to be between 200 and 300 DEG C, and hydrolyzing for 10 to 15 minutes; cooling hydrolysate, adjusting the pH value of the hydrolysate to be between 3 and 4, performing crystallization and filtration on the hydrolysate and obtaining coarse isonicotinic acid and filtrate; making the coarse isonicotinic acid subjected to hot-water dissolution, activated carbon decolorization, secondary crystallization and vacuum drying and obtaining isonicotinic acid products; adjusting the pH value of the filtrate to be between 8 and 9, performing crystallization and obtaining coarse pyrazinamide; and making the coarse pyrazinamide subjected to hot-water dissolution, activated carbon decolorization, secondary crystallization and vacuum drying and obtaining pyrazinamide products. The method does not add any catalyst during reaction, solves the pollution problem of acid and alkali catalyzed hydrolysis, has simple and green process, and has high purity and yield of the products.

Description

technical field [0001] The invention relates to amides and carboxylic acids, in particular to a method for simultaneously preparing isonicotinamide and isonicotinic acid in a near-critical water medium without catalysis. Background technique [0002] Isonicotinamide (Isonicotinamide; Pyridine-4-carboxylic acid amide), CAS NO.: 1453-82-3, chemical name 4-pyridine carboxamide, molecular formula C 6 h 6 N 2 O, molecular weight: 122.12, structural formula: White or off-white crystalline powder, melting point 155-157°C. [0003] As a pharmaceutical intermediate, isonicotinamide is mainly used to synthesize cephalosporins. Its structure is similar to nicotinamide, and it can play a bactericidal effect when entering cells. In the past, it was used as a second-line anti-tuberculosis drug without cross-resistance with other anti-tuberculosis drugs, and it was mainly used for cases in which first-line drug live therapy failed. Isonicotinamide alone is prone to drug resistance and...

AI Technical Summary

Problems solved by technology

The 4-cyanopyridine hydrolysis process has caused serious environmental pollution due to the use of a large amount of strong alkali catalysts, and the waste liquid treatment and catalyst recovery are not perfect; the isonicotinic acid dehydration process consumes a lot of power and high production costs; although the microbial method The emission of pollutants is less, but the process is more complex, and the reaction conditions are harsher, so it is difficult for large-scale industrial production

The obvious disadvantage of this process is that the process is complicated, the equipment investment is increased, the reaction process uses a large amount of strong alkali catalysts to cause serious environmental pollution, serious overoxidation, and the preparation, selection and recovery of metal catalysts are not yet perfect.

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