CN114394895A - Preparation method of 2,4, 6-trimethylphenylacetic acid - Google Patents
Preparation method of 2,4, 6-trimethylphenylacetic acid Download PDFInfo
- Publication number
- CN114394895A CN114394895A CN202210070693.6A CN202210070693A CN114394895A CN 114394895 A CN114394895 A CN 114394895A CN 202210070693 A CN202210070693 A CN 202210070693A CN 114394895 A CN114394895 A CN 114394895A
- Authority
- CN
- China
- Prior art keywords
- acid
- trimethylphenylacetic
- reaction
- preparing
- solvent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/10—Preparation of carboxylic acids or their salts, halides or anhydrides by reaction with carbon monoxide
- C07C51/14—Preparation of carboxylic acids or their salts, halides or anhydrides by reaction with carbon monoxide on a carbon-to-carbon unsaturated bond in organic compounds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of 2,4, 6-trimethylphenylacetic acid, which comprises the following steps: dissolving 2,4, 6-trimethylbenzyl chloride in a solvent to obtain a 2,4, 6-trimethylbenzyl chloride solution; adding the 2,4, 6-trimethylbenzyl chloride solution in the step one into a high-pressure reaction kettle, then adding an acid-binding agent, a palladium catalyst and a phosphine ligand, and introducing CO after nitrogen displacement; step three, continuously introducing CO, and carrying out carbonylation reaction under the conditions that the pressure of the CO is 0.5-3.5 Mpa and the temperature is 60-150 ℃; and step four, filtering and layering the system after the reaction in the step three, and adjusting acid with water phase to obtain the 2,4, 6-trimethylphenylacetic acid. The method takes 2,4, 6-trimethylbenzyl chloride as a raw material, and prepares the 2,4, 6-trimethylphenylacetic acid through one-step reaction through a palladium-catalyzed carbonylation reaction under the action of an acid-binding agent/palladium catalyst and a phosphine ligand, wherein the total yield reaches over 90 percent.
Description
Technical Field
The invention belongs to the technical field of fine chemical engineering, and particularly relates to a preparation method of 2,4, 6-trimethylphenylacetic acid.
Background
2,4, 6-trimethylphenylacetic acid is an organic intermediate, has excellent light resistance and heat resistance, and has wide application in chemical manufacture, such as being used as a photoinitiator in photopolymerisable materials and unsaturated resin models, being used as a stabilizer in plastics and paints, and being used for preparing antibiotics and antihistamines in medicines; can also be used for preparing coatings, dyes, molding compounds, adhesives, composite fiber materials and the like, and can also be used as an important intermediate of Spiromesifen (Spiromesifen) as an insecticide and acaricide.
There are currently three main routes for the preparation of 2,4, 6-trimethylphenylacetic acid: the 1, 3-dichloropropene method uses mesitylene and 1, 3-dichloropropene as raw materials, and produces 1-allyl mesitylene through Friedel-crafts reaction, and then the 1-allyl mesitylene is oxidized to obtain the product, and the method adopts 1, 3-dichloropropene, which has flammability and strong irritation, and has great harm to people and environment. The methanesulfonate method uses mesitylene and ethoxycarbonylmethyl methanesulfonate to make Friedel-crafts reaction to obtain ethoxycarbonylmethyl mesitylene, then uses concentrated hydrochloric acid to make hydrolysis to obtain the product. The cyano hydrolysis method is characterized in that mesitylene reacts with hydrochloric acid and formaldehyde to generate 2,4, 6-trimethyl benzyl chloride, then reacts with sodium cyanide to generate 2,4, 6-trimethyl benzyl cyanide, and hydrolysis is carried out to obtain a product. It is necessary to provide a method for preparing 2,4, 6-trimethylphenylacetic acid, which is suitable for industrial popularization, energy-saving, environment-friendly, simple in route and easy to operate.
Disclosure of Invention
The technical problem to be solved by the present invention is to provide a method for preparing 2,4, 6-trimethylphenylacetic acid, which is directed to the above-mentioned deficiencies of the prior art. The 2,4, 6-trimethylbenzyl chloride is used as a raw material, under the action of an acid-binding agent/palladium catalyst and a phosphine ligand, the 2,4, 6-trimethylphenylacetic acid is prepared by a palladium-catalyzed carbonylation reaction in one step, the total yield reaches over 90 percent, the method has the characteristics of greatly reducing reaction steps, reducing the formation of three wastes, avoiding using highly toxic NaCN, having high utilization rate of the raw material, being simple in synthesis method, being green and environment-friendly, and having good industrial value.
In order to solve the technical problems, the invention adopts the technical scheme that: a preparation method of 2,4, 6-trimethylphenylacetic acid is characterized by comprising the following steps:
dissolving 2,4, 6-trimethylbenzyl chloride in a solvent to obtain a 2,4, 6-trimethylbenzyl chloride solution;
adding the 2,4, 6-trimethylbenzyl chloride solution in the step one into a high-pressure reaction kettle, then adding an acid-binding agent, a palladium catalyst and a phosphine ligand, and introducing CO after nitrogen displacement;
step three, continuously introducing CO, and carrying out carbonylation reaction under the conditions that the pressure of the CO is 0.5-3.5 Mpa and the temperature is 60-150 ℃;
and step four, filtering and layering the system after the reaction in the step three, and adjusting acid with water phase to obtain the 2,4, 6-trimethylphenylacetic acid.
The preparation method of the 2,4, 6-trimethylphenylacetic acid is characterized in that the pressure in the third step is 1.0 Mpa-3.0 Mpa, and the temperature is 80-120 ℃.
The preparation method of 2,4, 6-trimethylphenylacetic acid is characterized in that, in the first step, the volume of the solvent is 4.5 to 7 times of the mass of 2,4, 6-trimethylchlorobenzyl chloride, the unit of the volume of the solvent is mL, and the unit of the mass of 2,4, 6-trimethylchlorobenzyl chloride is g.
The preparation method of 2,4, 6-trimethylphenylacetic acid is characterized in that in the first step, the solvent comprises water and an organic solvent, the volume of the water is 2-3 times of that of the organic solvent, and the organic solvent comprises one or more of isopropanol, tert-butyl alcohol, 2-methyltetrahydrofuran, acetonitrile, dichloromethane, 1, 2-dichloroethane, benzene and toluene.
The preparation method of the 2,4, 6-trimethylphenylacetic acid is characterized in that in the second step, the molar weight of the acid-binding agent is 0.3-2 times of that of the 2,4, 6-trimethylbenzyl chloride, and the acid-binding agent comprises one or more of potassium hydroxide, potassium carbonate, sodium hydroxide, calcium hydroxide, sodium methoxide, triethylamine, sodium acetate, sodium phosphate and N, N-diisopropylethylamine.
The preparation method of 2,4, 6-trimethylphenylacetic acid is characterized in that in the second step, the mass of the palladium catalyst is 0.1-1.5% of that of 2,4, 6-trimethylchlorobenzyl, and the palladium catalyst comprises PdCl2(PPh3)2、PdCl2(dppf)2、PdCl2(PhCN)2、PdCl2、Pd(OAc)2、Pd(PPh3)4And one or more of Pd/C.
The preparation method of 2,4, 6-trimethylphenylacetic acid is characterized in that in the second step, the mass of the phosphine ligand is 1% -3% of that of 2,4, 6-trimethylchlorobenzyl, and the phosphine ligand comprises PPh3One or more of dppf, dppp, dppb, dppe, xanthphos and Binap.
The preparation method of 2,4, 6-trimethylphenylacetic acid is characterized in that in the third step, the reaction time of the carbonylation reaction is 6-12 h.
The reaction equation for preparing the 2,4, 6-trimethylphenylacetic acid is as follows:
compared with the prior art, the invention has the following advantages:
1. the preparation method of the 2,4, 6-trimethylphenylacetic acid takes 2,4, 6-trimethylbenzyl chloride as a raw material, under the action of an acid binding agent, a palladium catalyst and a phosphine ligand, the 2,4, 6-trimethylphenylacetic acid is prepared through a palladium-catalyzed carbonylation reaction in one step, the total yield reaches more than 90 percent, and the preparation method has the characteristics of greatly reducing reaction steps, reducing the formation of three wastes, avoiding the use of virulent NaCN, high utilization rate of the raw material, simple synthesis method, environmental protection and good industrial value.
2. Preferably, the preparation method comprises the step of carrying out carbonylation reaction on a reaction system under the conditions that the pressure is 1.0-3.0 Mpa and the temperature is 80-120 ℃, and has the characteristic of higher yield, and the purity of the product can reach 99 percent at most.
The technical solution of the present invention is further described in detail with reference to the following examples.
Detailed Description
The reagents in the following examples are all commercially available.
Example 1
This example provides a method for preparing 2,4, 6-trimethylphenylacetic acid, which comprises:
step one, dissolving 100g of 2,4, 6-trimethylbenzyl chloride in 450mL of solvent to obtain a 2,4, 6-trimethylbenzyl chloride solution; the solvent comprises 300mL of water and 150mL of organic solvent, and the organic solvent is 2-methyltetrahydrofuran;
step two, adding the 2,4, 6-trimethylbenzyl chloride solution in the step one into a high-pressure reaction kettle, then adding 71g of an acid-binding agent, 0.5g of a palladium catalyst and 3g of a phosphine ligand, and introducing CO for displacement for three times after nitrogen displacement; the acid-binding agent is triethylamine; the palladium catalyst is PdCl2(PPh3)2(ii) a The phosphine ligand is PPh3；
Step three, continuously introducing CO, carrying out carbonylation reaction under the conditions that the pressure of the CO is 3.0Mpa and the temperature is 100 ℃ until the mass percentage content of the 2,4, 6-trimethylbenzyl chloride in the system is less than or equal to 1 percent, stopping the reaction, and the time of the carbonylation reaction is 12 hours;
and step four, cooling the system after the reaction in the step three, filtering, layering to obtain a water phase and an oil phase, adjusting the pH of the water phase to 2-3 by using a hydrochloric acid solution, and separating out a product to obtain 2,4, 6-trimethylphenylacetic acid.
The yield of 2,4, 6-trimethylphenylacetic acid obtained in this example was 95.1% and the purity 98.6%.
Example 2
This example provides a method for preparing 2,4, 6-trimethylphenylacetic acid, which comprises:
step one, dissolving 100g of 2,4, 6-trimethylbenzyl chloride in 600mL of solvent to obtain a 2,4, 6-trimethylbenzyl chloride solution; the solvent comprises 400mL of water and 200mL of organic solvent, and the organic solvent is toluene;
step two, adding the 2,4, 6-trimethylbenzyl chloride solution in the step one into a high-pressure reaction kettle, then adding 25g of an acid-binding agent, 1.5g of a palladium catalyst and 2g of a phosphine ligand, and introducing CO for displacement for three times after nitrogen displacement; the acid-binding agent is sodium hydroxide; the palladium catalyst is PdCl2(dppf)2(ii) a The phosphine ligand is dppf;
step three, continuously introducing CO, carrying out carbonylation reaction under the conditions that the pressure of CO is 2.0Mpa and the temperature is 120 ℃ until the mass percentage content of 2,4, 6-trimethylbenzyl chloride in the system is less than or equal to 1%, stopping the reaction, and the time of the carbonylation reaction is 10 hours;
and step four, cooling the system after the reaction in the step three, filtering, layering to obtain a water phase and an oil phase, adjusting the pH of the water phase to 2-3 by using a hydrochloric acid solution, and separating out a product to obtain 2,4, 6-trimethylphenylacetic acid.
The yield of 2,4, 6-trimethylphenylacetic acid obtained in this example was 92.2% and the purity was 99.0%.
Example 3
This example provides a method for preparing 2,4, 6-trimethylphenylacetic acid, which comprises:
step one, dissolving 100g of 2,4, 6-trimethylbenzyl chloride in 550mL of solvent to obtain a 2,4, 6-trimethylbenzyl chloride solution; the solvent comprises 400mL of water and 150mL of organic solvent, and the organic solvent is isopropanol;
step two, adding the 2,4, 6-trimethylbenzyl chloride solution in the step one into a high-pressure reaction kettle, then adding 70g of an acid-binding agent, 0.8g of a palladium catalyst and 2g of a phosphine ligand, and introducing CO for displacement for three times after nitrogen displacement; the acid-binding agent is potassium carbonate; the palladium catalyst is 5% Pd/C; the phosphine ligand is dppe;
step three, continuously introducing CO, carrying out carbonylation reaction under the conditions that the pressure of the CO is 1.5Mpa and the temperature is 110 ℃ until the mass percentage content of the 2,4, 6-trimethylbenzyl chloride in the system is less than or equal to 1 percent, stopping the reaction, and the time of the carbonylation reaction is 6 hours;
and step four, cooling the system after the reaction in the step three, filtering, layering to obtain a water phase and an oil phase, adjusting the pH of the water phase to 2-3 by using a hydrochloric acid solution, and separating out a product to obtain 2,4, 6-trimethylphenylacetic acid.
The yield of 2,4, 6-trimethylphenylacetic acid obtained in this example was 96.8% and the purity 98.5%.
Example 4
This example provides a method for preparing 2,4, 6-trimethylphenylacetic acid, which comprises:
step one, dissolving 100g of 2,4, 6-trimethylbenzyl chloride in 700mL of solvent to obtain a 2,4, 6-trimethylbenzyl chloride solution; the solvent comprises 500mL of water and 200mL of organic solvent, and the organic solvent is 1, 2-dichloroethane;
step two, adding the 2,4, 6-trimethylbenzyl chloride solution in the step one into a high-pressure reaction kettle, then adding 70g of an acid-binding agent, 0.1g of a palladium catalyst and 1.5g of a phosphine ligand, and introducing CO for displacement for three times after nitrogen displacement; the acid-binding agent is sodium acetate; the palladium catalyst is Pd (OAc)2(ii) a The phosphine ligand is dppb;
step three, continuously introducing CO, carrying out carbonylation reaction under the conditions that the pressure of the CO is 0.5Mpa and the temperature is 80 ℃ until the mass percentage content of the 2,4, 6-trimethylbenzyl chloride in the system is less than or equal to 1 percent, stopping the reaction, and the time of the carbonylation reaction is 10 hours;
and step four, cooling the system after the reaction in the step three, filtering, layering to obtain a water phase and an oil phase, adjusting the pH of the water phase to 2-3 by using a hydrochloric acid solution, and separating out a product to obtain 2,4, 6-trimethylphenylacetic acid.
The yield of 2,4, 6-trimethylphenylacetic acid obtained in this example was 91.8% and the purity was 99.2%.
Example 5
This example provides a method for preparing 2,4, 6-trimethylphenylacetic acid, which comprises:
step one, dissolving 100g of 2,4, 6-trimethylbenzyl chloride in 700mL of solvent to obtain a 2,4, 6-trimethylbenzyl chloride solution; the solvent comprises 500mL of water and 200mL of organic solvent, and the organic solvent is tert-butyl alcohol;
step two,Adding the 2,4, 6-trimethylbenzyl chloride solution obtained in the step one into a high-pressure reaction kettle, then adding 25g of an acid-binding agent, 0.5g of a palladium catalyst and 2g of a phosphine ligand, and introducing CO for displacement for three times after nitrogen displacement; the acid-binding agent is calcium hydroxide; the palladium catalyst is PdCl2(ii) a The phosphine ligand is Binap;
step three, continuously introducing CO, carrying out carbonylation reaction under the conditions that the pressure of the CO is 1.0Mpa and the temperature is 110 ℃ until the mass percentage content of the 2,4, 6-trimethylbenzyl chloride in the system is less than or equal to 1 percent, stopping the reaction, and the time of the carbonylation reaction is 10 hours;
and step four, cooling the system after the reaction in the step three, filtering, layering to obtain a water phase and an oil phase, adjusting the pH of the water phase to 2-3 by using a hydrochloric acid solution, and separating out a product to obtain 2,4, 6-trimethylphenylacetic acid.
The yield of 2,4, 6-trimethylphenylacetic acid obtained in this example was 93.1% and the purity 98.8%.
Example 6
This example provides a method for preparing 2,4, 6-trimethylphenylacetic acid, which comprises:
step one, dissolving 100g of 2,4, 6-trimethylbenzyl chloride in 700mL of solvent to obtain a 2,4, 6-trimethylbenzyl chloride solution; the solvent comprises 500mL of water and 200mL of organic solvent, and the organic solvent is benzene;
step two, adding the 2,4, 6-trimethylbenzyl chloride solution in the step one into a high-pressure reaction kettle, then adding 30g of an acid-binding agent, 0.5g of a palladium catalyst and 2g of a phosphine ligand, and introducing CO for displacement for three times after nitrogen displacement; the acid-binding agent is potassium hydroxide; the palladium catalyst is PdCl2(PhCN)2(ii) a The phosphine ligand is dppp;
step three, continuously introducing CO, carrying out carbonylation reaction under the conditions that the pressure of the CO is 0.5Mpa and the temperature is 60 ℃ until the mass percentage content of the 2,4, 6-trimethylbenzyl chloride in the system is less than or equal to 1 percent, stopping the reaction, and the time of the carbonylation reaction is 10 hours;
and step four, cooling the system after the reaction in the step three, filtering, layering to obtain a water phase and an oil phase, adjusting the pH of the water phase to 2-3 by using a hydrochloric acid solution, and separating out a product to obtain 2,4, 6-trimethylphenylacetic acid.
The yield of 2,4, 6-trimethylphenylacetic acid obtained in this example was 94.2% and the purity 98.5%.
Example 7
This example provides a method for preparing 2,4, 6-trimethylphenylacetic acid, which comprises:
step one, dissolving 100g of 2,4, 6-trimethylbenzyl chloride in 700mL of solvent to obtain a 2,4, 6-trimethylbenzyl chloride solution; the solvent comprises 500mL of water and 200mL of organic solvent, and the organic solvent is acetonitrile;
step two, adding the 2,4, 6-trimethylbenzyl chloride solution in the step one into a high-pressure reaction kettle, then adding 40g of an acid-binding agent, 0.8g of a palladium catalyst and 2g of a phosphine ligand, and introducing CO for displacement for three times after nitrogen displacement; the acid-binding agent is sodium carbonate; the palladium catalyst is Pd (PPh)3)4(ii) a The phosphine ligand is Xantphos;
step three, continuously introducing CO, carrying out carbonylation reaction under the conditions that the pressure of the CO is 3.5Mpa and the temperature is 150 ℃ until the mass percentage content of the 2,4, 6-trimethylbenzyl chloride in the system is less than or equal to 1 percent, stopping the reaction, and the time of the carbonylation reaction is 10 hours;
and step four, cooling the system after the reaction in the step three, filtering, layering to obtain a water phase and an oil phase, adjusting the pH of the water phase to 2-3 by using a hydrochloric acid solution, and separating out a product to obtain 2,4, 6-trimethylphenylacetic acid.
The yield of 2,4, 6-trimethylphenylacetic acid obtained in this example was 96.3% and the purity 98.7%.
Example 8
This example provides a method for preparing 2,4, 6-trimethylphenylacetic acid, which comprises:
step one, dissolving 100g of 2,4, 6-trimethylbenzyl chloride in 600mL of solvent to obtain a 2,4, 6-trimethylbenzyl chloride solution; the solvent comprises 400mL of water and 200mL of organic solvent, and the organic solvent is dichloromethane;
step two, adding the 2,4, 6-trimethylbenzyl chloride solution in the step one into a high-pressure reaction kettle, then adding 35g of an acid-binding agent, 1g of a palladium catalyst and 3g of a phosphine ligand, and introducing CO for displacement for three times after nitrogen displacement; the acid-binding agent is sodium phosphate; the palladium catalyst is PdCl2(PPh3)2And PdCl2(dppf)2The PdCl2(PPh3)2And PdCl2(dppf)2The ratio of the amounts of substances (1): 1; the phosphine ligand is PPh3Dppf and dppp, said PPh3The mass ratio of dppf to dppp is 1: 1: 1;
step three, continuously introducing CO, carrying out carbonylation reaction under the conditions that the pressure of the CO is 0.8Mpa and the temperature is 70 ℃ until the mass percentage content of the 2,4, 6-trimethylbenzyl chloride in the system is less than or equal to 1 percent, stopping the reaction, and the time of the carbonylation reaction is 6 hours;
and step four, cooling the system after the reaction in the step three, filtering, layering to obtain a water phase and an oil phase, adjusting the pH of the water phase to 2-3 by using a hydrochloric acid solution, and separating out a product to obtain 2,4, 6-trimethylphenylacetic acid.
The yield of 2,4, 6-trimethylphenylacetic acid obtained in this example was 93.1% and the purity 98.3%.
Example 9
This example provides a method for preparing 2,4, 6-trimethylphenylacetic acid, which comprises:
step one, dissolving 100g of 2,4, 6-trimethylbenzyl chloride in 600mL of solvent to obtain a 2,4, 6-trimethylbenzyl chloride solution; the solvent comprises 400mL of water and 200mL of organic solvent, the organic solvent is dichloromethane and toluene, and the mass ratio of the dichloromethane to the toluene is 1: 1;
step two, adding the 2,4, 6-trimethylbenzyl chloride solution in the step one into a high-pressure reaction kettle, then adding 80g of an acid-binding agent, 1.5g of a palladium catalyst and 2g of a phosphine ligand, and introducing CO for displacement for three times after nitrogen displacement; the acid-binding agent is N, N-diisopropylethylamine; the palladium catalyst is PdCl2(PhCN)2、PdCl2、Pd(OAc)2And Pd (PPh)3)4The PdCl2(PhCN)2、PdCl2、Pd(OAc)2And Pd (PPh)3)4The ratio of the amounts of substances is 1: 1: 1: 1; the phosphine ligands are dppb, dppe, Xantphos and Binap, and the mass ratio of dppb to dppe to Xantphos to Binap is 1:2:2: 1;
step three, continuously introducing CO, carrying out carbonylation reaction under the conditions that the pressure of the CO is 3.5Mpa and the temperature is 150 ℃ until the mass percentage content of the 2,4, 6-trimethylbenzyl chloride in the system is less than or equal to 1 percent, stopping the reaction, and the time of the carbonylation reaction is 12 hours;
and step four, cooling the system after the reaction in the step three, filtering, layering to obtain a water phase and an oil phase, adjusting the pH of the water phase to 2-3 by using a hydrochloric acid solution, and separating out a product to obtain 2,4, 6-trimethylphenylacetic acid.
The yield of 2,4, 6-trimethylphenylacetic acid obtained in this example was 96.6% and the purity 98.5%.
Example 10
This example provides a method for preparing 2,4, 6-trimethylphenylacetic acid, which comprises:
step one, dissolving 100g of 2,4, 6-trimethylbenzyl chloride in 550mL of solvent to obtain a 2,4, 6-trimethylbenzyl chloride solution; the solvent comprises 400mL of water and 150mL of organic solvent, the organic solvent is isopropanol, tert-butanol and 2-methyltetrahydrofuran, and the mass ratio of the isopropanol, the tert-butanol and the 2-methyltetrahydrofuran is 1:2: 1;
step two, adding the 2,4, 6-trimethylbenzyl chloride solution in the step one into a high-pressure reaction kettle, then adding 25g of an acid-binding agent, 1.2g of a palladium catalyst and 2g of a phosphine ligand, and introducing CO for displacement for three times after nitrogen displacement; the acid-binding agent is calcium hydroxide, sodium methoxide, triethylamine and sodium acetate, and the mass ratio of the calcium hydroxide to the sodium methoxide to the triethylamine to the sodium acetate is 1: 1: 1: 1; the palladium catalyst is Pd (PPh)3)4And 5% Pd/C, the Pd (PPh)3)4And 5% Pd/C in a ratio of 1: 2; the phosphine ligands are dppf, dppp, dppb and dppe, and the mass ratio of dppf to dppp to dppb to dppe is 1:2:2: 1;
step three, continuously introducing CO, carrying out carbonylation reaction under the conditions that the pressure of the CO is 3.5Mpa and the temperature is 130 ℃ until the mass percentage content of the 2,4, 6-trimethylbenzyl chloride in the system is less than or equal to 1 percent, stopping the reaction, and the time of the carbonylation reaction is 8 hours;
and step four, cooling the system after the reaction in the step three, filtering, layering to obtain a water phase and an oil phase, adjusting the pH of the water phase to 2-3 by using a hydrochloric acid solution, and separating out a product to obtain 2,4, 6-trimethylphenylacetic acid.
The yield of 2,4, 6-trimethylphenylacetic acid obtained in this example was 95.5% and the purity 98.9%.
Example 11
This example provides a method for preparing 2,4, 6-trimethylphenylacetic acid, which comprises:
step one, dissolving 100g of 2,4, 6-trimethylbenzyl chloride in 600mL of solvent to obtain a 2,4, 6-trimethylbenzyl chloride solution; the solvent comprises 450mL of water and 150mL of organic solvent, the organic solvent is acetonitrile, dichloromethane, 1, 2-dichloroethane, benzene and toluene, and the mass ratio of the acetonitrile to the dichloromethane to the 1, 2-dichloroethane to the benzene to the toluene is 1:2: 1: 1: 2;
step two, adding the 2,4, 6-trimethylbenzyl chloride solution in the step one into a high-pressure reaction kettle, then adding 26g of an acid-binding agent, 0.5g of a palladium catalyst and 1g of a phosphine ligand, and introducing CO for displacement for three times after nitrogen displacement; the acid-binding agent is potassium hydroxide, potassium carbonate, sodium hydroxide and sodium methoxide, and the mass ratio of the potassium hydroxide to the potassium carbonate to the sodium hydroxide to the sodium methoxide is 1:2:2:2: 1; the palladium catalyst is PdCl2(PhCN)2、PdCl2And Pd (OAc)2The PdCl2(PhCN)2、PdCl2And Pd (OAc)2The ratio of the amounts of substances (1): 2: 2; the phosphine ligands are dppp, dppb, dppe, Xantphos and Binap, and the mass ratio of dppp, dppb, dppe, Xantphos to Binap is 1:2: 1: 1: 1;
step three, continuously introducing CO, carrying out carbonylation reaction under the conditions that the pressure of the CO is 3.2Mpa and the temperature is 150 ℃ until the mass percentage content of the 2,4, 6-trimethylbenzyl chloride in the system is less than or equal to 1 percent, stopping the reaction, and the time of the carbonylation reaction is 10 hours;
and step four, cooling the system after the reaction in the step three, filtering, layering to obtain a water phase and an oil phase, adjusting the pH of the water phase to 2-3 by using a hydrochloric acid solution, and separating out a product to obtain 2,4, 6-trimethylphenylacetic acid.
The yield of 2,4, 6-trimethylphenylacetic acid obtained in this example was 90.6% and the purity 98.2%.
Example 12
This example provides a method for preparing 2,4, 6-trimethylphenylacetic acid, which comprises:
step one, dissolving 100g of 2,4, 6-trimethylbenzyl chloride in 600mL of solvent to obtain a 2,4, 6-trimethylbenzyl chloride solution; the solvent comprises 500mL of water and 200mL of organic solvent, the organic solvent is isopropanol, tert-butanol and 2-methyltetrahydrofuran, and the mass ratio of the isopropanol, the tert-butanol and the 2-methyltetrahydrofuran is 1:2: 1;
step two, adding the 2,4, 6-trimethylbenzyl chloride solution in the step one into a high-pressure reaction kettle, then adding 90g of an acid-binding agent, 0.3g of a palladium catalyst and 2g of a phosphine ligand, and introducing CO for displacement for three times after nitrogen displacement; the acid-binding agent is calcium hydroxide; the palladium catalyst is PdCl2And Pd (OAc)2The PdCl2And Pd (OAc)2The ratio of the amounts of substances (1): 1; the phosphine ligand is Binap;
step three, continuously introducing CO, carrying out carbonylation reaction under the conditions that the CO pressure is 3.5Mpa and the temperature is 140 ℃ until the mass percentage content of the 2,4, 6-trimethylbenzyl chloride in the system is less than or equal to 1%, stopping the reaction, and the carbonylation reaction time is 12 hours;
and step four, cooling the system after the reaction in the step three, filtering, layering to obtain a water phase and an oil phase, adjusting the pH of the water phase to 2-3 by using a hydrochloric acid solution, and separating out a product to obtain 2,4, 6-trimethylphenylacetic acid.
The yield of 2,4, 6-trimethylphenylacetic acid obtained in this example was 94.6% and the purity 98.7%.
The above description is only a preferred embodiment of the present invention, and is not intended to limit the present invention, and all simple modifications, changes and equivalent structural changes made to the above embodiment according to the technical spirit of the present invention still fall within the protection scope of the technical solution of the present invention.
Claims (8)
1. A preparation method of 2,4, 6-trimethylphenylacetic acid is characterized by comprising the following steps:
dissolving 2,4, 6-trimethylbenzyl chloride in a solvent to obtain a 2,4, 6-trimethylbenzyl chloride solution;
adding the 2,4, 6-trimethylbenzyl chloride solution in the step one into a high-pressure reaction kettle, then adding an acid-binding agent, a palladium catalyst and a phosphine ligand, and introducing CO after nitrogen displacement;
step three, continuously introducing CO, and carrying out carbonylation reaction under the conditions that the pressure of the CO is 0.5-3.5 Mpa and the temperature is 60-150 ℃;
and step four, filtering and layering the system after the reaction in the step three, and adjusting acid with water phase to obtain the 2,4, 6-trimethylphenylacetic acid.
2. The method for preparing 2,4, 6-trimethylphenylacetic acid according to claim 1, wherein the pressure in the third step is 1.0MPa to 3.0MPa, and the temperature is 80 ℃ to 120 ℃.
3. The method for preparing 2,4, 6-trimethylphenylacetic acid according to claim 1, wherein in the first step, the volume of the solvent is 4.5 to 7 times of the mass of 2,4, 6-trimethylchlorobenzyl chloride, the volume of the solvent is mL, and the mass of the 2,4, 6-trimethylchlorobenzyl chloride is g.
4. The method for preparing 2,4, 6-trimethylphenylacetic acid according to claim 1, wherein in the first step, the solvent comprises water and an organic solvent, the volume of the water is 2 times to 3 times that of the organic solvent, and the organic solvent comprises one or more of isopropanol, tert-butanol, 2-methyltetrahydrofuran, acetonitrile, dichloromethane, 1, 2-dichloroethane, benzene and toluene.
5. The method for preparing 2,4, 6-trimethylphenylacetic acid according to claim 1, wherein in the second step, the molar amount of the acid-binding agent is 0.3-2 times of that of 2,4, 6-trimethylchlorobenzyl chloride, and the acid-binding agent comprises one or more of potassium hydroxide, potassium carbonate, sodium hydroxide, calcium hydroxide, sodium methoxide, triethylamine, sodium acetate, sodium phosphate and N, N-diisopropylethylamine.
6. The method for preparing 2,4, 6-trimethylphenylacetic acid according to claim 1, wherein in the second step, the mass of the palladium catalyst is 0.1-1.5% of that of the 2,4, 6-trimethylchlorobenzyl chloride, and the palladium catalyst comprises PdCl2(PPh3)2、PdCl2(dppf)2、PdCl2(PhCN)2、PdCl2、Pd(OAc)2、Pd(PPh3)4And one or more of Pd/C.
7. The method for preparing 2,4, 6-trimethylphenylacetic acid according to claim 1, wherein in the second step, the mass of the phosphine ligand is 1-3% of that of 2,4, 6-trimethylchlorobenzyl, and the phosphine ligand comprises PPh3One or more of dppf, dppp, dppb, dppe, xanthphos and Binap.
8. The method for preparing 2,4, 6-trimethylphenylacetic acid according to claim 1, wherein the reaction time of the carbonylation reaction in the third step is 6-12 h.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210070693.6A CN114394895B (en) | 2022-01-21 | 2022-01-21 | Preparation method of 2,4, 6-trimethylphenylacetic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210070693.6A CN114394895B (en) | 2022-01-21 | 2022-01-21 | Preparation method of 2,4, 6-trimethylphenylacetic acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114394895A true CN114394895A (en) | 2022-04-26 |
| CN114394895B CN114394895B (en) | 2023-09-15 |
Family
ID=81233466
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210070693.6A Active CN114394895B (en) | 2022-01-21 | 2022-01-21 | Preparation method of 2,4, 6-trimethylphenylacetic acid |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114394895B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115246762A (en) * | 2022-08-25 | 2022-10-28 | 上海朴颐化学科技有限公司 | Preparation method of 2,4,5-trifluorophenylacetic acid |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1039241A (en) * | 1988-07-05 | 1990-01-31 | 中国科学院兰州化学物理所 | Process for preparing phenylacetic acid by chlorobenzyl carbonylation under normal pressure |
| CN1284406A (en) * | 2000-06-21 | 2001-02-21 | 华中科技大学 | Catalyst for catalytic carboxylation to synthesize phenylacetic acid |
| CN102140062A (en) * | 2011-03-13 | 2011-08-03 | 联化科技股份有限公司 | Method for preparing 2,5-dimethyl phenylacetic acid |
| CN103804176A (en) * | 2014-01-22 | 2014-05-21 | 东南大学 | Synthesis method for 2, 5-dimethyl phenylacetic acid |
| CN109320413A (en) * | 2017-08-01 | 2019-02-12 | 江苏联化科技有限公司 | A kind of preparation method of phenylacetic acid class compound |
-
2022
- 2022-01-21 CN CN202210070693.6A patent/CN114394895B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1039241A (en) * | 1988-07-05 | 1990-01-31 | 中国科学院兰州化学物理所 | Process for preparing phenylacetic acid by chlorobenzyl carbonylation under normal pressure |
| CN1284406A (en) * | 2000-06-21 | 2001-02-21 | 华中科技大学 | Catalyst for catalytic carboxylation to synthesize phenylacetic acid |
| CN102140062A (en) * | 2011-03-13 | 2011-08-03 | 联化科技股份有限公司 | Method for preparing 2,5-dimethyl phenylacetic acid |
| CN103804176A (en) * | 2014-01-22 | 2014-05-21 | 东南大学 | Synthesis method for 2, 5-dimethyl phenylacetic acid |
| CN109320413A (en) * | 2017-08-01 | 2019-02-12 | 江苏联化科技有限公司 | A kind of preparation method of phenylacetic acid class compound |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115246762A (en) * | 2022-08-25 | 2022-10-28 | 上海朴颐化学科技有限公司 | Preparation method of 2,4,5-trifluorophenylacetic acid |
Also Published As
| Publication number | Publication date |
|---|---|
| CN114394895B (en) | 2023-09-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN114394895A (en) | Preparation method of 2,4, 6-trimethylphenylacetic acid | |
| CN109293565B (en) | Preparation method of fluopyram | |
| WO2012122747A1 (en) | A method for preparing 2,5-dimethylphenylacetic acid | |
| CN102002013A (en) | Preparation method of 6-amino-7-fluoro-1,4-benzoxazine-3(4H)-ketone | |
| CN105439895A (en) | Preparation method of N (4-aminobenzoyl)-L-glutamic acid | |
| CN106242990B (en) | Preparation method of 2-amino-4-acetamino anisole | |
| CN104861116A (en) | Preparation method of fluorine-containing soap-free emulsion repellent | |
| CN107384357A (en) | Polyoxyethylene-benzene sulfonate type composite gemini surfactant and preparation method thereof | |
| CN101648839A (en) | Green synthesis method of bromomethylbiphenyl compound | |
| KR20080046611A (en) | An improved process for the preparation of losartan | |
| CN106397304B (en) | A kind of production method of 1- bromines carbazole | |
| KR101421514B1 (en) | Method for preparing isosorbide from sorbitol using water-compatible lewis acid | |
| CN115819251B (en) | Preparation method of (1R) -1- [3- (difluoromethyl) -2-fluorophenyl ] ethylamine | |
| CN104628943A (en) | Acrylamide copolymer, as well as preparation method and application thereof | |
| CN111004146A (en) | Liquid azophenyl molecular solar thermal fuel and synthesis method and application thereof | |
| CN101307019B (en) | Method for preparing N-amino-3-azabicyclo[3,3,0]octane hydrochloride | |
| CN103788073A (en) | Novel method for preparing voriconazole key intermediate | |
| CN109354590B (en) | Synthesis method of thiacloprid | |
| CN110028470B (en) | Process method for producing dehydroacetic acid, patchoulenone and analogues thereof by using carbon dioxide | |
| CN112552345A (en) | Preparation method of NK-1 receptor antagonist | |
| CN112521421A (en) | Preparation method of pharmaceutical compound | |
| CN111303481A (en) | Oligomeric hindered amine light stabilizer and preparation method thereof | |
| CN103319358B (en) | Preparation method of 7-amino heptanoic acid | |
| CN112759562B (en) | Preparation method of high-purity hydrobromic acid vortioxetine | |
| CN114426516B (en) | Preparation method of 2-amino-3-bromopyridine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |