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CN-122010732-A - Synthesis method of n-octyl 2- (4-chloro-2-methylphenoxy) propionate

CN122010732ACN 122010732 ACN122010732 ACN 122010732ACN-122010732-A

Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of n-octyl 2- (4-chloro-2-methylphenoxy) propionate. The synthesis method comprises the following steps of (1) taking D (+) -lactide and octanol sodium to carry out ring opening reaction in the presence of a Lewis acid catalyst to obtain (2R) -2-octyl hydroxy propionate, (2) taking (2R) -2-octyl hydroxy propionate and 4-chloro-2-methylphenol to carry out O-arylation coupling reaction in the presence of a copper catalyst and inorganic base to obtain the 2- (4-chloro-2-methylphenoxy) n-octyl 2- (4-chloro-2-methylphenoxy) propionate. The invention innovatively adopts a two-step method route of metal catalysis ring opening and copper catalysis O-arylation, and provides a novel technical idea with conciseness, high efficiency and good optical selectivity for synthesizing chiral phenoxycarboxylic acid ester.

Inventors

  • ZHAO HUALING
  • HU RONG
  • ZHENG DEBING

Assignees

  • 湖南亚王医药科技有限公司

Dates

Publication Date
20260512
Application Date
20260130

Claims (8)

  1. 1. The synthesis method of the n-octyl 2- (4-chloro-2-methylphenoxy) propionate is characterized by comprising the following steps: (1) In the presence of a Lewis acid catalyst, carrying out ring opening reaction on D (+) -lactide and n-octanol sodium to obtain (2R) -2-octyl hydroxy acrylate; (2) And (3) carrying out O-arylation coupling reaction on the (2R) -2-hydroxy octyl propionate and 4-chloro-2-methylphenol in the presence of a copper catalyst and inorganic base to obtain the 2- (4-chloro-2-methylphenoxy) n-octyl propionate.
  2. 2. The method for synthesizing n-octyl 2- (4-chloro-2-methylphenoxy) propionate according to claim 1, wherein the lewis acid catalyst in step (1) is tetrabutyl titanate.
  3. 3. The method for synthesizing n-octyl 2- (4-chloro-2-methylphenoxy) propionate according to claim 2, wherein the molar ratio of D-lactide to n-octanol sodium in the step (1) is 1-1.2, and the dosage ratio of n-octanol sodium to catalyst is 10 mmol (0.05-0.06) mL.
  4. 4. The method for synthesizing n-octyl 2- (4-chloro-2-methylphenoxy) propionate according to claim 1, wherein the temperature of the ring-opening reaction in the step (1) is 25 to 30 ℃ and the time is 6 to 8 h.
  5. 5. The method for synthesizing n-octyl 2- (4-chloro-2-methylphenoxy) propionate according to claim 1, wherein the copper catalyst in the step (2) comprises a monovalent copper salt and a carbon nitride material, and the inorganic base is any one of potassium tert-butoxide, sodium tert-butoxide and sodium methoxide.
  6. 6. The method for synthesizing n-octyl 2- (4-chloro-2-methylphenoxy) propionate according to claim 5, wherein the carbon nitride material is polymeric carbon nitride.
  7. 7. The method for synthesizing n-octyl 2- (4-chloro-2-methylphenoxy) propionate according to claim 5, wherein the ratio of the amount of the octyl (2R) -2-hydroxypropionate, 4-chloro-2-methylphenol, copper catalyst and inorganic base used in the step (2) is 1 mmol (1.25-1.5) mmol (5-6) mg (3-4) mmol.
  8. 8. The method for synthesizing n-octyl 2- (4-chloro-2-methylphenoxy) propionate according to claim 1, wherein the O-arylation coupling reaction is carried out in a sealed environment at a temperature of 70-80 ℃ for a time of 18-20 h.

Description

Synthesis method of n-octyl 2- (4-chloro-2-methylphenoxy) propionate Technical Field The invention belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of n-octyl 2- (4-chloro-2-methylphenoxy) propionate. Background N-octyl 2- (4-chloro-2-methylphenoxy) propionate, particularly its (R) -isomer, is an effective chiral plant growth regulator and root inhibitor. Currently, the synthesis of this compound relies mainly on classical multi-step derivatization routes starting from chiral lactate esters. Patent CN107473962A discloses a method for preparing a target product by using L-ethyl lactate as a raw material through three steps of sulfonation, etherification and transesterification. The process is well-defined and readily available, but has the advantages that firstly, the synthesis route involves three separate reactions and corresponding separation and purification processes, the overall yield is affected by the multi-step cumulative effect, the process efficiency is improved, secondly, the transesterification reaction is carried out in the final step, which is usually carried out at a higher temperature (> 120 ℃) and in the presence of a metal catalyst, and there is a risk of higher energy consumption and slight racemization of the chiral center at high temperatures, and finally, the route uses sulfonyl chloride reagents, which require special attention for storage and use, and the reaction produces stoichiometric byproducts. With the development of biocatalysis and transition metal catalysis technology, a new tool is provided for the efficient and high-selectivity synthesis of chiral molecules. Therefore, there is an urgent need in the art to explore a new synthetic route that has a simpler step, can more gently construct key chemical bonds, and can more precisely control chiral centers, to enrich the means of preparation of the important compounds, and to provide alternative options for process optimization. Disclosure of Invention In order to overcome the defects of the prior art, the primary aim of the invention is to provide a method for synthesizing n-octyl 2- (4-chloro-2-methylphenoxy) propionate. The invention innovatively adopts a two-step method route of metal catalysis ring opening and copper catalysis O-arylation, wherein the first step adopts a Lewis acid catalyst to realize high-selectivity ring opening of D-lactide to octanol sodium, chiral intermediates are obtained in extremely high yield, and the second step adopts copper catalysis cross coupling reaction to efficiently construct key C-O-Ar aromatic ether bonds, thereby providing a simple, efficient and brand-new technical idea with good optical selectivity for synthesizing chiral phenoxycarboxylate. The aim of the invention is achieved by the following technical scheme: a method for synthesizing n-octyl 2- (4-chloro-2-methylphenoxy) propionate comprises the following steps: (1) In the presence of a Lewis acid catalyst, carrying out ring opening reaction on D (+) -lactide and n-octanol sodium to obtain (2R) -2-octyl hydroxy acrylate; (2) And (3) carrying out O-arylation coupling reaction on the (2R) -2-hydroxy octyl propionate and 4-chloro-2-methylphenol in the presence of a copper catalyst and inorganic base to obtain the 2- (4-chloro-2-methylphenoxy) n-octyl propionate. Further, in the step (1), the lewis acid catalyst is tetrabutyl titanate. Further, in the step (1), the molar ratio of the D-lactide to the n-octanol sodium is (1-1.2) 1, and the dosage ratio of the n-octanol sodium to the catalyst is 10 mmol (0.05-0.06) mL. Further, the temperature of the ring-opening reaction in the step (1) is 25-30 ℃ and the time is 6-8 h. Further, the copper catalyst in the step (2) comprises a monovalent copper salt and a carbon nitride material, and the inorganic base is selected from any one of potassium tert-butoxide, sodium tert-butoxide or sodium methoxide. Further, the carbon nitride material is polymeric carbon nitride. The carbon nitride material is a polymer semiconductor material composed of carbon and nitrogen elements, such as common graphite phase carbon nitride (g-C 3N4), and the rich nitrogen sites can be used as ligand to stabilize copper catalyst, so as to improve the catalytic efficiency. Further, the preparation method of the copper catalyst comprises the steps of dispersing carbon nitride materials in water, mixing with acetonitrile dispersion containing monovalent copper salt, and evaporating the solvent after ultrasonic treatment. Further, the dosage ratio of (2R) -2-hydroxy octyl acrylate, 4-chloro-2-methylphenol, copper catalyst and inorganic base in the step (2) is 1 mmol (1.25-1.5) mmol (5-6) mg (3-4) mmol. Further, the O-arylation coupling reaction is carried out in a sealed environment at a temperature of 70-80 ℃ for a time of 18-20 h. Compared with the prior art, the invention has the following effects: 1. The invention provides a brand new synthetic path, creatively adopts