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CN-117700452-B - Preparation method of 4- (hydroxymethyl phosphono) -2-carbonyl butyric acid

CN117700452BCN 117700452 BCN117700452 BCN 117700452BCN-117700452-B

Abstract

The invention provides a preparation method of 4- (hydroxy methyl phosphonic group) -2-carbonyl butyric acid, which comprises the following steps of a) mixing methyl phosphonic acid diester, carboxylic acid and acryloyl chloride, carrying out addition reaction, obtaining (3-chloro-3-carbonyl propyl) methyl phosphonic acid ester feed liquid after reduced pressure distillation, b) mixing the (3-chloro-3-carbonyl propyl) methyl phosphonic acid ester feed liquid obtained in the step a) with sodium cyanide, a solvent and a catalyst, carrying out substitution reaction, purifying to obtain (3-cyano-3-carbonyl propyl) methyl phosphonic acid ester feed liquid, C) uniformly mixing the (3-cyano-3-carbonyl propyl) methyl phosphonic acid ester feed liquid obtained in the step b) with water, cooling to 10-40 ℃, then dropwise adding hydrochloric acid for acidification, continuing stirring for 0.1-1 h after dropwise addition, carrying out hydrolysis reaction, and finally carrying out purification treatment to obtain the 4- (hydroxy methyl phosphonic group) -2-carbonyl butyric acid. Compared with the prior art, the preparation method provided by the invention has the advantages of simple process steps, mild reaction conditions and higher comprehensive utilization rate of elements.

Inventors

  • YANG LIRONG
  • ZHOU SHUGUANG
  • ZHOU HAISHENG
  • QIN LONG
  • WU JIANPING
  • YU SHENLUAN
  • WANG LINLIN
  • ZHAN BO
  • WANG PING

Assignees

  • 浙江新安化工集团股份有限公司
  • 浙江大学

Dates

Publication Date
20260505
Application Date
20220908

Claims (10)

  1. 1. A method for preparing 4- (hydroxy methyl phosphonic group) -2-carbonyl butyric acid, comprising the following steps: a) Mixing methylphosphonous diester, carboxylic acid and acryloyl chloride, performing addition reaction, and distilling under reduced pressure to obtain (3-chloro-3-carbonyl propyl) methylphosphonic ester feed liquid; b) Mixing the (3-chloro-3-carbonyl propyl) methylphosphonate feed liquid obtained in the step a) with sodium cyanide, a solvent and a catalyst, and carrying out substitution reaction, thus obtaining (3-cyano-3-carbonyl propyl) methylphosphonate feed liquid after purification, wherein the catalyst is one or more selected from cuprous chloride, cuprous bromide, cuprous iodide, ferric chloride, ferrous bromide, ferrous iodide, zinc chloride, zinc bromide and zinc iodide; c) Uniformly mixing the (3-cyano-3-carbonyl propyl) methylphosphonate feed liquid obtained in the step b) with water, cooling to 10-40 ℃, dropwise adding hydrochloric acid for acidification, continuously stirring for 0.1-1h after the dropwise adding is finished, then carrying out hydrolysis reaction, and finally purifying to obtain the 4- (hydroxymethyl-phosphono) -2-carbonyl butyric acid.
  2. 2. The process according to claim 1, wherein the methylphosphonous diester of step a) is selected from one or more of the group consisting of dimethyl methylphosphonous, diethyl methylphosphonous, dipropyl methylphosphonous and dibutyl methylphosphonous; the carboxylic acid is selected from one or more of acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid and isovaleric acid; The mass ratio of the methylphosphonous diester to the carboxylic acid is 1 (1-20); the molar ratio of the acrylic chloride to the methylphosphonous diester is (0.8-1.5): 1.
  3. 3. The method according to claim 1, wherein the mixing in step a) is specifically: And (3) under the stirring condition, placing the methylphosphonous diester into carboxylic acid, controlling the temperature to be 0-40 ℃, and simultaneously dropwise adding the acryloyl chloride for 0.1-5 h to complete the mixing process.
  4. 4. The preparation method according to claim 1, wherein the temperature of the addition reaction in step a) is 0 ℃ to 90 ℃ and the time is 1h to 10h.
  5. 5. The process according to claim 1, wherein in step b) the solvent is acetonitrile or butyronitrile; The mass ratio of the solvent to the methylphosphonous acid diester is (1-20) 1, and the molar ratio of the sodium cyanide to the catalyst to the methylphosphonous acid diester is (0.8-1.5) 0.002-0.02.
  6. 6. The method according to claim 1, wherein the temperature of the substitution reaction in step b) is 80 ℃ to 120 ℃ for 1h to 12h.
  7. 7. The method according to claim 1, wherein the molar ratio of hydrochloric acid to methylphosphonous diester in step c) is (1-5): 1.
  8. 8. The method according to claim 1, wherein the acidification temperature in step C) is 0 ℃ to 40 ℃.
  9. 9. The method according to claim 1, wherein the hydrolysis reaction in step C) is carried out at a temperature of 60 ℃ to 130 ℃ for a period of 1h to 24h.
  10. 10. The method according to claim 1, wherein the purification treatment in step c) is performed by: and (3) removing acid water from a product obtained by the hydrolysis reaction under reduced pressure, adding acetone for dissolving, filtering to remove insoluble salts, and adding methyl isobutyl ketone into filtrate for crystallization to obtain 4- (hydroxymethyl phosphono) -2-carbonyl butyric acid.

Description

Preparation method of 4- (hydroxymethyl phosphono) -2-carbonyl butyric acid Technical Field The invention relates to the technical field of chemical industry, in particular to a preparation method of a pesticide intermediate 4- (hydroxy methyl phosphono) -2-carbonyl butyric acid. Background 4- (Hydroxy methyl phosphono) -2-carbonyl butyric acid, PPO or keto acid for short, is an important intermediate in the synthesis process of glufosinate-ammonium, the compound can obtain glufosinate-ammonium through steps such as ammonification reduction, and L-glufosinate-ammonium can be obtained through biological enzymatic conversion. In 1980, the FBC company first filed patent US4399287A for a keto acid intermediate, and 3- (ethoxymethylphosphono) propionate extended by claisen condensation to form the keto acid intermediate 2-oxo-4- (hydroxymethylacyl) butanoic acid, with a reported isolated yield of keto acid intermediate of about 30%. In 1991, hoechst reported a chemical synthesis method of 4- (hydroxymethyl phosphono) -2-carbonyl butyric acid (J.org. chem.1991,56, 1783-1788) that 3- (ethoxymethyl phosphono) -ethyl propionate is prepared by Michael addition of monoethyl methylphosphonate and ethyl acrylate under the action of sodium ethoxide, then claisen ester condensation is performed between-50 ℃ and diethyl oxalate under the action of sodium ethoxide, and 4- (hydroxymethyl phosphono) -2-carbonyl butyric acid is prepared by decarboxylation of hydrochloric acid, but the method needs to be performed at-50 ℃ and has low overall yield, a large amount of waste water is generated, and the crystallization time of the product is up to 48 hours, and the reaction formula is as follows: the patent CN103665032A discloses a preparation method of glufosinate, which reports a method for preparing important intermediate 4- (hydroxy- (methyl) phosphinyl) -2-oxobutanoic acid of glufosinate by using a keto acid route, takes oxygen-containing and phosphorus five-membered heterocyclic 2, 5-dioxo-1-oxa-2-phospholane and cyanide as raw materials, carries out a cyanation reaction in an organic solvent to generate a ketocyanide compound, then carries out a hydrolysis process in an acid solution to obtain keto acid substance 4- (hydroxy- (methyl) phosphinyl) -2-oxobutanoic acid, and finally carries out an ammonification and hydrogenation reduction process under the conditions of an alcohol solvent and a catalyst to obtain the glufosinate. However, the cyclic phosphonic anhydride used in the method is difficult to prepare, has high cost and is difficult to purify. Patent CN105218579a discloses a method for synthesizing L-type glufosinate ammonium salt, wherein 4- (hydroxymethyl phosphono) -2-carbonyl butyric acid which is an important intermediate is prepared from 4- (ethoxy- (methyl) phosphino) -2-acetoxybutyl cyanide by hydrolysis with hydrochloric acid to obtain 4- (hydroxy- (methyl) phosphino) 2-hydroxybutyric acid, neutralizing with sodium hydroxide to form salt, oxidizing with sodium hypochlorite aqueous solution to obtain sodium 4- (hydroxy sodium- (methyl) phosphino) 2-carbonyl butyrate under the catalysis of transition metal oxide, and finally introducing HCl gas to react for desalting to obtain 4- (hydroxymethyl phosphono) -2-carbonyl butyric acid. However, this method requires a large amount of acid and alkali to produce a large amount of byproduct salt, and also requires noble metal as a catalyst, which increases the cost and makes the byproduct salt difficult to treat. Disclosure of Invention In view of the above, the invention aims to provide a preparation method of 4- (hydroxy methyl phosphonic acid) -2-carbonyl butyric acid, which has the advantages of short process steps, mild reaction conditions and high comprehensive utilization rate of elements. The invention provides a preparation method of 4- (hydroxy methyl phosphonic group) -2-carbonyl butyric acid, which comprises the following steps: a) Mixing methylphosphonous diester, carboxylic acid and acryloyl chloride, performing addition reaction, and distilling under reduced pressure to obtain (3-chloro-3-carbonyl propyl) methylphosphonic ester feed liquid; b) Mixing the (3-chloro-3-carbonyl propyl) methylphosphonate feed liquid obtained in the step a) with sodium cyanide, a solvent and a catalyst, performing substitution reaction, and purifying to obtain (3-cyano-3-carbonyl propyl) methylphosphonate feed liquid; c) Uniformly mixing the (3-cyano-3-carbonyl propyl) methylphosphonate feed liquid obtained in the step b) with water, cooling to 10-40 ℃, dropwise adding hydrochloric acid for acidification, continuously stirring for 0.1-1h after the dropwise adding is finished, then carrying out hydrolysis reaction, and finally purifying to obtain the 4- (hydroxymethyl-phosphono) -2-carbonyl butyric acid. Preferably, the methylphosphonous diester in step a) is selected from one or more of the group consisting of dimethyl methylphosphonous, diethyl methylphosphonous, dipropyl me