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CN-122010755-A - O-chlorophenylglycine production process

CN122010755ACN 122010755 ACN122010755 ACN 122010755ACN-122010755-A

Abstract

The invention relates to the technical field of chemical synthesis, and particularly discloses a production process of o-chlorophenylglycine, which aims at the defects of low yield of the existing process route and large loss of products in wastewater, a novel extractant is adopted to effectively extract the products in the wastewater, the extracted extraction solution containing the products is backwashed and extracted by dilute sulfuric acid, so that sulfuric acid solution containing the products is obtained, the solution is used for process neutralization, the yield of the process route is improved to more than 85%, the used extraction phase can be repeatedly recycled through experiments, the production cost is not increased additionally, the loss of the extraction phase in the process of multiple times of recycling is small, and the cost in the recycling process is low.

Inventors

  • LUO JIANQING
  • LI ZHONGXIN
  • ZHANG WANGBIN
  • HE TAO

Assignees

  • 九江中星医药化工有限公司

Dates

Publication Date
20260512
Application Date
20250709

Claims (10)

  1. 1. A process for preparing o-chlorobenzeneglycine includes such steps as preparing N-chlorobenzeneglycine, Step 1, mixing alkali, alcohol and sodium cyanide, adding o-chlorobenzaldehyde, and controlling the temperature to obtain a first mixture; step 2, mixing the first mixture, water and alkali, and controlling the temperature to obtain a second mixture; step 3, adding activated carbon into the second mixture for adsorption and separation to obtain a water phase system; Step 4, adjusting the pH of the water phase system; step 5, temperature control crystallization is carried out to obtain a finished product o-chlorophenylglycine and o-chlorophenylglycine wastewater B; Step 6, extracting the o-chlorophenylglycine wastewater B by using extraction to obtain an upper layer loaded extraction phase and a lower layer raffinate; and 7, adding acid into the upper layer loaded extraction phase to obtain a neutralized acid water layer A and a regenerated extraction phase.
  2. 2. The process for producing o-chlorophenylglycine according to claim 1, wherein the neutralized acid aqueous layer a obtained in the step 7 is used for adjusting the pH of the aqueous system in the step 4.
  3. 3. The process according to any one of claims 1 or 2, wherein the regenerated extract phase obtained in step 7 is used as the extract phase in step 6, and the o-chlorophenylglycine wastewater B is extracted in step 6 to obtain an upper loaded extract phase and a lower raffinate phase.
  4. 4. A process according to any one of claims 1 to 3, wherein the alcohol in step 1 is selected from any one or a mixture of methanol, ethanol and isopropanol, and/or the alkali in step 1 is selected from any one or a combination of sodium hydroxide, sodium tert-butoxide, potassium tert-butoxide and ammonium bicarbonate, and/or the mass of alkali added per 1kg of alcohol in step 1 is 500-800 g, and/or the mass of sodium cyanide added per 1kg of alcohol in step 1 is 400-750 g, and/or the mass of o-chlorobenzaldehyde added per 1kg of alcohol in step 1 is 400-600 g, and/or the temperature is controlled to 50-70 ℃.
  5. 5. The process according to any one of claims 1 to 4, wherein the mass of the liquid alkali added to each 1L of water in the step 2 is 1.0-2.0 kg, and/or the temperature is controlled to 120-160 ℃.
  6. 6. The process according to any one of claims 1 to 5, wherein the pH of the aqueous phase system is adjusted to 6.5 to 7.0 in step 4.
  7. 7. The process according to any one of claims 1 to 6, wherein the temperature-controlled crystallization in the step 5 is performed by controlling the temperature to 20-30 ℃.
  8. 8. The process for producing o-chlorophenylglycine according to any one of claims 1 to 7, wherein the mixing volume ratio of the extracted phase to the o-chlorophenylglycine wastewater B in the step 6 is 1 (8-12), and/or the extraction temperature in the step 6 is 2-35 ℃, and/or the mass fraction of the o-chlorophenylglycine in the o-chlorophenylglycine wastewater B is 1-2 wt%, and/or the acid in the step 7 is one or more selected from sulfuric acid, hydrochloric acid and nitric acid, and/or the mass fraction of the acid is 15-25%, and/or the pH of the aqueous phase system in the step 4 is adjusted to 6.5-7.0 by using the neutralized acid aqueous layer A in the step 4.
  9. 9. The process for producing o-chlorophenylglycine according to claim 8, wherein the diluent comprises one or more of sulfonated kerosene, cyclohexane and n-octanol, and/or the extraction ternary mixture comprises a first extractant, a second extractant and a third extractant, wherein the first extractant, the second extractant and the third extractant are independently selected from one or more of bis (2-ethylhexyl) phosphate, monophenyl (benzyl) phosphonate, 4-methyl-3-pentene-2-ketoxime, dioctyl phthalate, 5-dodecyl-2-hydroxybenzoaldoxime and tributyl phosphate.
  10. 10. The production process of o-chlorophenylglycine according to claim 9, wherein the mixing volume ratio of sulfonated kerosene and cyclohexane in the diluent is (1-4) 1, and/or the feeding mole ratio of the first extractant to the second extractant in the extraction ternary mixture is (8-12) 1-3, and/or the feeding mole ratio of the second extractant to the third extractant in the extraction ternary mixture is (1-3) 5-9.

Description

O-chlorophenylglycine production process Technical Field The invention relates to the technical field of organic wastewater treatment, in particular to a production process of o-chlorophenylglycine and a wastewater treatment method thereof. Background O-chlorophenylglycine is an important intermediate of clopidogrel (chopidogrel) used for preventing and treating heart, brain and other arterial circulatory disorder diseases caused by platelet high aggregation. Despite the various synthetic routes for their preparation, most of the current industrial applications still use the Bucherer-Bergs process for the preparation of o-chlorophenylglycine. Referring to CN 101058547A, CN105237421A, CN11468530A and other patents, o-chlorobenzaldehyde, ammonium bicarbonate and sodium cyanide are taken as raw materials, and are subjected to cyclization to obtain o-chlorobenzohydantoin, alkaline hydrolysis and acidification to obtain o-chlorobenzeneglycine, wherein the process route is shown in formula 1. Preparation of O-chlorophenylglycine by using Bucherer-Bergs method The process route has the characteristics of stable product quality, good economic benefit and the like, but the yield of the process route is only 70-75%, the problem of low yield exists, the main reason that the yield of the process route is low is obtained by analysis through carrying out the overall process HPLC central control and system material balance accounting on the process is that about 10-15% of o-chlorophenylglycine is dissolved in centrifugal wastewater, about 10T wastewater is produced when 1T product is prepared in workshop production, and the yield of the product lost in the wastewater accounts for 10-15% of the theoretical yield and is identical with the HPLC central control result and material balance. Therefore, how to effectively recycle the products in the o-chlorophenylglycine wastewater is the most direct method for improving the process yield. Disclosure of Invention In view of the problems existing in the prior art, a first aspect of the present invention provides a process for producing o-chlorophenylglycine, comprising, Step 1, mixing alkali, alcohol and sodium cyanide, adding o-chlorobenzaldehyde, and controlling the temperature to obtain a first mixture; step 2, mixing the first mixture, water and alkali, and controlling the temperature to obtain a second mixture; step 3, adding activated carbon into the second mixture for adsorption and separation to obtain a water phase system; Step 4, adjusting the pH of the water phase system; step 5, temperature control crystallization is carried out to obtain a finished product o-chlorophenylglycine, and o-chlorophenylglycine wastewater B; Step 6, extracting the o-chlorophenylglycine wastewater B by using extraction to obtain an upper layer loaded extraction phase and a lower layer raffinate; and 7, adding acid into the upper layer loaded extraction phase to obtain a neutralized acid water layer A and a regenerated extraction phase. In some embodiments of the o-chlorophenylglycine production process set forth in the first aspect, the neutralized acid aqueous layer a obtained in the step 7 is used for adjusting pH of the aqueous phase system in the step 4. In some embodiments of the o-chlorophenylglycine production process set forth in the first aspect, the regenerated extract phase obtained in the step 7 is used as the extract phase in the step 6, and the o-chlorophenylglycine wastewater B in the step 6 is extracted to obtain an upper loaded extract phase and a lower raffinate. In some embodiments of the o-chlorophenylglycine production process set forth in the first aspect, the alcohol in step 1 is selected from any one or a mixture of methanol, ethanol and isopropanol. In some embodiments of the o-chlorophenylglycine production process set forth in the first aspect, the base in step 1 is selected from any one or a combination of sodium hydroxide, sodium tert-butoxide, potassium tert-butoxide, and ammonium bicarbonate. In some embodiments of the o-chlorophenylglycine production process provided in the first aspect, the mass of the alkali added in each 1kg of alcohol in the step 1 is 500-800 g, and in some embodiments of the o-chlorophenylglycine production process provided in the first aspect, the mass of the alkali added in each 1kg of alcohol in the step 1 is optionally 600g, 650g, 700g, 750g, 800g. In some embodiments of the o-chlorophenylglycine production process set forth in the first aspect, the mass of sodium cyanide added in each 1kg of alcohol in the step 1 is 400-750 g, and in some embodiments of the o-chlorophenylglycine production process set forth in the first aspect, the mass of sodium cyanide added in each 1kg of alcohol in the step 1 is optionally 450g, 500g, 550g, 600g, 650g, 700g. In some embodiments of the o-chlorobenzoic acid production process proposed in the first aspect, the mass of o-chlorobenzaldehyde added in each 1kg of alcohol in step 1 is 400-600 g, and in s