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

A near-critical water and isonicotinamide technology, applied in organic chemistry and other directions, can solve the problems of complex process, difficult large-scale industrial production, harsh reaction conditions, etc., and achieve the effect of solving pollution problems, realizing greening, and simple reaction process.

Inactive Publication Date: 2009-07-08
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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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 rea

Method used

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

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Add 240g of deionized water and 120g of isonicotonitrile (the mass ratio of deionized water to isoniazid is 2:1) in a 500mL intermittent autoclave, start stirring, heat up to boiling under normal pressure, open the exhaust valve for 5min, Use steam to remove the air in the kettle; close the exhaust valve, continue to heat up to 200 ° C for 150 minutes; add HCl solution to adjust the pH value to 3-4 after the reaction product is cooled, and filter to obtain the crude isonicotinic acid and the filtrate containing isonicotinamide after crystallization . The crude product of isonicotinic acid was dissolved in hot water, decolorized by active carbon, secondary crystallization, and dried in vacuum to obtain 25.8g of isonicotinic acid product, the product was analyzed by HPLC with a purity of 97.5% (wt%) and a yield of 17.7%; Add NaOH solution to the amide filtrate to adjust the pH value to 8-9, and crystallize to obtain crude isonicotinamide; the crude isonicotinamide is diss...

Embodiment 2

[0034] Add 300g of deionized water and 100g of isonicotonitrile (mass ratio of deionized water to isonicotonitrile is 3:1) in a 500mL intermittent autoclave, start stirring, heat up to boiling under normal pressure, open the exhaust valve for 4min, Use water vapor to remove the air in the kettle; close the exhaust valve, continue to heat up to 210 ° C for 135 minutes; add H after the reaction product is cooled 2 SO 4 The pH value of the solution is adjusted to 3-4, and the crude product of isonicotinic acid and the filtrate containing isonicotinamide are obtained by filtering after crystallization. The crude product of isonicotinic acid was dissolved in hot water, decolorized with activated carbon, secondary crystallized, and vacuum dried to obtain 22.5g of isonicotinic acid product. The purity of the product was analyzed by HPLC to be 97.7% (wt%), and the yield was 18.6%. Add Na to the amide filtrate 2 CO 3 Adjust the pH value of the solution to 8-9 and crystallize to obta...

Embodiment 3

[0036] Add 300g of deionized water and 60g of isonicotonitrile (mass ratio of deionized water to isonicotonitrile is 5:1) in a 500mL intermittent autoclave, start stirring, heat up to boiling under normal pressure, open the exhaust valve for 3min, Use steam to remove the air in the kettle; close the exhaust valve, continue to heat up to 220 ° C for 120 minutes; add HCl solution to adjust the pH value to 3-4 after the reaction product is cooled, and filter to obtain the crude isonicotinic acid and the filtrate containing isonicotinamide after crystallization . The crude product of isonicotinic acid was dissolved in hot water, decolorized by active carbon, secondary crystallization, and vacuum dried to obtain 15.4g of isonicotinic acid product, the product was analyzed by HPLC with a purity of 97.8% (wt%) and a yield of 21.2%; Add KOH solution to the amide filtrate to adjust the pH value to 8-9, and crystallize to obtain crude isonicotinamide; the crude isonicotinamide is dissol...

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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...

Claims

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Application Information

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IPC IPC(8): C07D213/81C07D213/803C07D213/79
Inventor 吕秀阳任浩明
Owner ZHEJIANG UNIV
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