CN114394895B - Preparation method of 2,4, 6-trimethylphenylacetic acid - Google Patents
Preparation method of 2,4, 6-trimethylphenylacetic acid Download PDFInfo
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Abstract
The invention discloses a preparation method of 2,4, 6-trimethylphenylacetic acid, which comprises the following steps: step one, dissolving 2,4, 6-trimethyl benzyl chloride in a solvent to obtain a 2,4, 6-trimethyl benzyl chloride solution; step two, adding the 2,4, 6-trimethyl benzyl chloride solution obtained in the step one into a high-pressure reaction kettle, adding an acid binding agent, a palladium catalyst and a phosphine ligand, and introducing CO after nitrogen replacement; continuously introducing CO, and performing carbonylation reaction under the condition that the CO pressure is 0.5-3.5 Mpa and the temperature is 60-150 ℃; and step four, filtering, layering and adjusting acid in water phase of the system after the reaction in the step three to obtain the 2,4, 6-trimethylphenylacetic acid. The method takes 2,4, 6-trimethyl benzyl chloride as a raw material, and the 2,4, 6-trimethylphenylacetic acid is prepared through a palladium-catalyzed carbonylation reaction under the action of an acid binding agent/palladium catalyst and phosphine ligand, and the total yield reaches more than 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, has wide application in chemical manufacturing, can be used as a photoinitiator in photopolymerisable materials and unsaturated resin models, can be used as a stabilizer in plastics and paint, and can be used for preparing antibiotics and antihistamine medicines in medicines; the Spiromesifen can also be used for preparing paints, dyes, molding, adhesives, composite fiber materials and the like, and can also be used as an important intermediate of Spiromesifen (Spiromesifen) for killing insects and acaricides.
At present, the preparation of 2,4, 6-trimethylphenylacetic acid mainly comprises the following three routes: the 1, 3-dichloropropene method takes mesitylene and 1, 3-dichloropropene as raw materials, generates 1-allyl mesitylene through Friedel-crafts reaction, and then oxidizes to obtain a product. The method of methanesulfonate uses mesitylene and ethoxycarbonyl methyl methanesulfonate to make Friedel-crafts reaction to obtain ethoxycarbonyl methyl mesitylene, then uses concentrated hydrochloric acid to make hydrolysis so as to obtain the invented product. The cyano hydrolysis method is characterized in that mesitylene, hydrochloric acid and formaldehyde react to generate 2,4, 6-trimethyl chlorobenzyl, then the 2,4, 6-trimethyl cyanobenzyl is generated by reacting with sodium cyanide, and the hydrolysis is carried out to obtain a product. The method for preparing the 2,4, 6-trimethylphenylacetic acid is energy-saving, environment-friendly, simple in route and easy to operate, and is suitable for industrial popularization.
Disclosure of Invention
The technical problem to be solved by the invention is to provide a preparation method of 2,4, 6-trimethylphenylacetic acid aiming at the defects of the prior art. The invention takes 2,4, 6-trimethyl benzyl chloride as raw material, and prepares the 2,4, 6-trimethylphenylacetic acid by palladium catalyzed carbonylation reaction under the action of acid-binding agent/palladium catalyst and phosphine ligand, the total yield reaches more than 90 percent, and the invention has the characteristics of greatly reducing reaction steps, reducing three wastes, avoiding the use of virulent NaCN, having high raw material utilization rate, simple synthesis method, being environment-friendly and having good industrialized value.
In order to solve the technical problems, the invention adopts the following technical scheme: a method for preparing 2,4, 6-trimethylphenylacetic acid, comprising the steps of:
step one, dissolving 2,4, 6-trimethyl benzyl chloride in a solvent to obtain a 2,4, 6-trimethyl benzyl chloride solution;
step two, adding the 2,4, 6-trimethyl benzyl chloride solution obtained in the step one into a high-pressure reaction kettle, adding an acid binding agent, a palladium catalyst and a phosphine ligand, and introducing CO after nitrogen replacement;
continuously introducing CO, and performing carbonylation reaction under the condition that the CO pressure is 0.5-3.5 Mpa and the temperature is 60-150 ℃;
and step four, filtering, layering and adjusting acid in water phase of the system after the reaction in the step three 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 ℃ to 120 ℃.
The preparation method of the 2,4, 6-trimethylphenylacetic acid is characterized in that in the first step, the volume of the solvent is 4.5-7 times of the mass of 2,4, 6-trimethylchlorobenzyl chloride, the volume of the solvent is in mL, and the mass of the 2,4, 6-trimethylchlorobenzyl chloride is in g.
The preparation method of the 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 that of the organic solvent, and the organic solvent comprises one or more of isopropanol, tertiary butanol, 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 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.
The preparation method of the 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 the mass of 2,4, 6-trimethylchlorobenzyl, and the palladium catalyst comprises PdCl 2 (PPh 3 ) 2 、PdCl 2 (dppf) 2 、PdCl 2 (PhCN) 2 、PdCl 2 、Pd(OAc) 2 、Pd(PPh 3 ) 4 And one or more of Pd/C.
The preparation method of the 2,4, 6-trimethylphenylacetic acid is characterized in that in the second step, the mass of the phosphine ligand is 2,1 to 3 percent of the mass of the 4, 6-trimethyl chlorobenzyl, wherein the phosphine ligand comprises PPh 3 One or more of dppf, dppp, dppb, dppe, xantphos 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 2,4, 6-trimethylphenylacetic acid takes 2,4, 6-trimethylchlorobenzyl chloride as raw material, and the 2,4, 6-trimethylphenylacetic acid is prepared by one-step reaction through palladium-catalyzed carbonylation under the action of an acid binding agent, a palladium catalyst and a phosphine ligand, the total yield reaches more than 90 percent, and the preparation method has the characteristics of greatly reducing the reaction steps, reducing the formation of three wastes, avoiding the use of extremely toxic NaCN, having high raw material utilization rate, being simple in synthesis method and being green and environment-friendly, and has good industrialized value.
2. Preferably, the preparation method of the invention comprises the step of carrying out carbonylation reaction under the condition that the pressure is 1.0 Mpa-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 scheme of the invention is further described in detail below with reference to the examples.
Detailed Description
Reagents in the following examples are commercially available.
Example 1
The embodiment provides a preparation method of 2,4, 6-trimethylphenylacetic acid, which comprises the following steps:
step one, 100g of 2,4, 6-trimethyl benzyl chloride is dissolved in 450mL of solvent to obtain 2,4, 6-trimethyl benzyl chloride solution; the solvent comprises 300mL of water and 150mL of organic solvent, wherein the organic solvent is 2-methyltetrahydrofuran;
step two, adding the 2,4, 6-trimethyl benzyl chloride solution obtained in the step one into a high-pressure reaction kettle, adding 71g of acid binding agent, 0.5g of palladium catalyst and 3g of phosphine ligand, and introducing CO for three times after nitrogen replacement; the acid binding agent is triethylamine; the palladium catalyst is PdCl 2 (PPh 3 ) 2 The method comprises the steps of carrying out a first treatment on the surface of the The phosphine ligand is PPh 3 ；
Continuously introducing CO, and carrying out carbonylation reaction under the condition that the CO pressure is 3.0Mpa and the temperature is 100 ℃ until the mass percent of 2,4, 6-trimethyl chlorobenzyl in the system is less than or equal to 1%, stopping the reaction, wherein 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, regulating the pH of the water phase to 2-3 by using a hydrochloric acid solution, and separating out a product to obtain the 2,4, 6-trimethylphenylacetic acid.
The yield of 2,4, 6-trimethylphenylacetic acid obtained in this example was 95.1% and the purity was 98.6%.
Example 2
The embodiment provides a preparation method of 2,4, 6-trimethylphenylacetic acid, which comprises the following steps:
step one, 100g of 2,4, 6-trimethyl benzyl chloride is dissolved in 600mL of solvent to obtain 2,4, 6-trimethyl benzyl chloride solution; the solvent comprises 400mL of water and 200mL of organic solvent, wherein the organic solvent is toluene;
step two, adding the 2,4, 6-trimethyl benzyl chloride solution obtained in the step one into a high-pressure reaction kettle, adding 25g of an acid binding agent, 1.5g of a palladium catalyst and 2g of a phosphine ligand, and introducing CO for three times after nitrogen replacement; the acid binding agent is sodium hydroxide; the palladium catalyst is PdCl 2 (dppf) 2 The method comprises the steps of carrying out a first treatment on the surface of the The phosphine ligand is dppf;
continuously introducing CO, and carrying out carbonylation reaction under the condition that the CO pressure is 2.0Mpa and the temperature is 120 ℃ until the mass percent of 2,4, 6-trimethyl chlorobenzyl in the system is less than or equal to 1%, stopping the reaction, wherein the carbonylation reaction time 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, regulating the pH of the water phase to 2-3 by using a hydrochloric acid solution, and separating out a product to obtain the 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
The embodiment provides a preparation method of 2,4, 6-trimethylphenylacetic acid, which comprises the following steps:
step one, 100g of 2,4, 6-trimethyl benzyl chloride is dissolved in 550mL of solvent to obtain 2,4, 6-trimethyl benzyl chloride solution; the solvent comprises 400mL of water and 150mL of organic solvent, wherein the organic solvent is isopropanol;
step two, adding the 2,4, 6-trimethyl benzyl chloride solution obtained in the step one into a high-pressure reaction kettle, adding 70g of an acid binding agent, 0.8g of a palladium catalyst and 2g of a phosphine ligand, and introducing CO for three times after nitrogen replacement; the acid binding agent is potassium carbonate; the palladium catalyst is 5% Pd/C; the phosphine ligand is dppe;
continuously introducing CO, and carrying out carbonylation reaction under the condition that the CO pressure is 1.5Mpa and the temperature is 110 ℃ until the mass percent of 2,4, 6-trimethyl chlorobenzyl in the system is less than or equal to 1%, stopping the reaction, wherein the carbonylation reaction time 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, regulating the pH of the water phase to 2-3 by using a hydrochloric acid solution, and separating out a product to obtain the 2,4, 6-trimethylphenylacetic acid.
The yield of 2,4, 6-trimethylphenylacetic acid obtained in this example was 96.8% and the purity was 98.5%.
Example 4
The embodiment provides a preparation method of 2,4, 6-trimethylphenylacetic acid, which comprises the following steps:
step one, 100g of 2,4, 6-trimethyl benzyl chloride is dissolved in 700mL of solvent to obtain 2,4, 6-trimethyl benzyl chloride solution; the solvent comprises 500mL of water and 200mL of organic solvent, wherein the organic solvent is 1, 2-dichloroethane;
step two, adding the 2,4, 6-trimethyl benzyl chloride solution obtained in the step one into a high-pressure reaction kettle, then adding 70g of acid binding agent, 0.1g of palladium catalyst and 1.5g of phosphine ligand,introducing CO for three times after nitrogen replacement; the acid binding agent is sodium acetate; the palladium catalyst is Pd (OAc) 2 The method comprises the steps of carrying out a first treatment on the surface of the The phosphine ligand is dppb;
continuously introducing CO, and carrying out carbonylation reaction under the condition that the CO pressure is 0.5Mpa and the temperature is 80 ℃ until the mass percent of 2,4, 6-trimethyl chlorobenzyl in the system is less than or equal to 1%, stopping the reaction, wherein the carbonylation reaction time 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, regulating the pH of the water phase to 2-3 by using a hydrochloric acid solution, and separating out a product to obtain the 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
The embodiment provides a preparation method of 2,4, 6-trimethylphenylacetic acid, which comprises the following steps:
step one, 100g of 2,4, 6-trimethyl benzyl chloride is dissolved in 700mL of solvent to obtain 2,4, 6-trimethyl benzyl chloride solution; the solvent comprises 500mL of water and 200mL of organic solvent, wherein the organic solvent is tertiary butanol;
step two, adding the 2,4, 6-trimethyl benzyl chloride solution obtained in the step one into a high-pressure reaction kettle, adding 25g of an acid binding agent, 0.5g of a palladium catalyst and 2g of a phosphine ligand, and introducing CO for three times after nitrogen replacement; the acid binding agent is calcium hydroxide; the palladium catalyst is PdCl 2 The method comprises the steps of carrying out a first treatment on the surface of the The phosphine ligand is Binap;
continuously introducing CO, and carrying out carbonylation reaction under the condition that the CO pressure is 1.0Mpa and the temperature is 110 ℃ until the mass percent of 2,4, 6-trimethyl chlorobenzyl in the system is less than or equal to 1%, stopping the reaction, wherein the carbonylation reaction time 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, regulating the pH of the water phase to 2-3 by using a hydrochloric acid solution, and separating out a product to obtain the 2,4, 6-trimethylphenylacetic acid.
The yield of 2,4, 6-trimethylphenylacetic acid obtained in this example was 93.1% and the purity was 98.8%.
Example 6
The embodiment provides a preparation method of 2,4, 6-trimethylphenylacetic acid, which comprises the following steps:
step one, 100g of 2,4, 6-trimethyl benzyl chloride is dissolved in 700mL of solvent to obtain 2,4, 6-trimethyl benzyl chloride solution; the solvent comprises 500mL of water and 200mL of organic solvent, wherein the organic solvent is benzene;
step two, adding the 2,4, 6-trimethyl benzyl chloride solution obtained in the step one into a high-pressure reaction kettle, adding 30g of an acid binding agent, 0.5g of a palladium catalyst and 2g of a phosphine ligand, and introducing CO for three times after nitrogen replacement; the acid binding agent is potassium hydroxide; the palladium catalyst is PdCl 2 (PhCN) 2 The method comprises the steps of carrying out a first treatment on the surface of the The phosphine ligand is dppp;
continuously introducing CO, and carrying out carbonylation reaction under the condition that the CO pressure is 0.5Mpa and the temperature is 60 ℃ until the mass percent of 2,4, 6-trimethyl chlorobenzyl in the system is less than or equal to 1%, stopping the reaction, wherein the carbonylation reaction time 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, regulating the pH of the water phase to 2-3 by using a hydrochloric acid solution, and separating out a product to obtain the 2,4, 6-trimethylphenylacetic acid.
The yield of 2,4, 6-trimethylphenylacetic acid obtained in this example was 94.2% and the purity was 98.5%.
Example 7
The embodiment provides a preparation method of 2,4, 6-trimethylphenylacetic acid, which comprises the following steps:
step one, 100g of 2,4, 6-trimethyl benzyl chloride is dissolved in 700mL of solvent to obtain 2,4, 6-trimethyl benzyl chloride solution; the solvent comprises 500mL of water and 200mL of organic solvent, wherein the organic solvent is acetonitrile;
step two, adding the 2,4, 6-trimethyl benzyl chloride solution obtained in the step one into a high-pressure reaction kettle, adding 40g of an acid binding agent, 0.8g of a palladium catalyst and 2g of a phosphine ligand, and introducing CO for three times after nitrogen replacement; the acid binding agent is sodium carbonate; the palladium catalyst is Pd (PPh) 3 ) 4 The method comprises the steps of carrying out a first treatment on the surface of the The phosphine ligand is Xantphos;
continuously introducing CO, and carrying out carbonylation reaction under the condition that the CO pressure is 3.5Mpa and the temperature is 150 ℃ until the mass percent of 2,4, 6-trimethyl chlorobenzyl in the system is less than or equal to 1%, stopping the reaction, wherein the carbonylation reaction time 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, regulating the pH of the water phase to 2-3 by using a hydrochloric acid solution, and separating out a product to obtain the 2,4, 6-trimethylphenylacetic acid.
The yield of 2,4, 6-trimethylphenylacetic acid obtained in this example was 96.3% and the purity was 98.7%.
Example 8
The embodiment provides a preparation method of 2,4, 6-trimethylphenylacetic acid, which comprises the following steps:
step one, 100g of 2,4, 6-trimethyl benzyl chloride is dissolved in 600mL of solvent to obtain 2,4, 6-trimethyl benzyl chloride solution; the solvent comprises 400mL of water and 200mL of organic solvent, wherein the organic solvent is dichloromethane;
step two, adding the 2,4, 6-trimethyl benzyl chloride solution obtained in the step one into a high-pressure reaction kettle, adding 35g of an acid binding agent, 1g of a palladium catalyst and 3g of a phosphine ligand, and introducing CO for three times after nitrogen replacement; the acid binding agent is sodium phosphate; the palladium catalyst is PdCl 2 (PPh 3 ) 2 And PdCl 2 (dppf) 2 The PdCl 2 (PPh 3 ) 2 And PdCl 2 (dppf) 2 The ratio of the amounts of the substances is 1:1, a step of; the phosphine ligand is PPh 3 Dppf and dppp, the PPh 3 The mass ratio of dppf to dppp is 1:1:1, a step of;
continuously introducing CO, and carrying out carbonylation reaction under the condition that the CO pressure is 0.8Mpa and the temperature is 70 ℃ until the mass percent of 2,4, 6-trimethyl chlorobenzyl in the system is less than or equal to 1%, stopping the reaction, wherein the carbonylation reaction time 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, regulating the pH of the water phase to 2-3 by using a hydrochloric acid solution, and separating out a product to obtain the 2,4, 6-trimethylphenylacetic acid.
The yield of 2,4, 6-trimethylphenylacetic acid obtained in this example was 93.1% and the purity was 98.3%.
Example 9
The embodiment provides a preparation method of 2,4, 6-trimethylphenylacetic acid, which comprises the following steps:
step one, 100g of 2,4, 6-trimethyl benzyl chloride is dissolved in 600mL of solvent to obtain 2,4, 6-trimethyl benzyl chloride solution; the solvent comprises 400mL of water and 200mL of organic solvent, wherein the organic solvent is dichloromethane and toluene, and the mass ratio of the dichloromethane to the toluene is 1:1, a step of;
step two, adding the 2,4, 6-trimethyl benzyl chloride solution obtained in the step one into a high-pressure reaction kettle, adding 80g of acid binding agent, 1.5g of palladium catalyst and 2g of phosphine ligand, and introducing CO for three times after nitrogen replacement; the acid binding agent is N, N-diisopropylethylamine; the palladium catalyst is PdCl 2 (PhCN) 2 、PdCl 2 、Pd(OAc) 2 And Pd (PPh) 3 ) 4 The PdCl 2 (PhCN) 2 、PdCl 2 、Pd(OAc) 2 And Pd (PPh) 3 ) 4 The ratio of the amounts of the substances is 1:1:1:1, a step of; the phosphine ligands are dppb, dppe, xantphos and Binap, and the mass ratio of dppb, dppe, xantphos to Bina is 1:2:2:1, a step of;
continuously introducing CO, and carrying out carbonylation reaction under the condition that the CO pressure is 3.5Mpa and the temperature is 150 ℃ until the mass percent of 2,4, 6-trimethyl chlorobenzyl in the system is less than or equal to 1%, stopping the reaction, wherein 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, regulating the pH of the water phase to 2-3 by using a hydrochloric acid solution, and separating out a product to obtain the 2,4, 6-trimethylphenylacetic acid.
The yield of 2,4, 6-trimethylphenylacetic acid obtained in this example was 96.6% and the purity was 98.5%.
Example 10
The embodiment provides a preparation method of 2,4, 6-trimethylphenylacetic acid, which comprises the following steps:
step one, 100g of 2,4, 6-trimethyl benzyl chloride is dissolved in 550mL of solvent to obtain 2,4, 6-trimethyl benzyl chloride solution; the solvent comprises 400mL of water and 150mL of organic solvent, wherein the organic solvent is isopropanol, tertiary butanol and 2-methyltetrahydrofuran, and the mass ratio of the isopropanol to the tertiary butanol to the 2-methyltetrahydrofuran is 1:2:1, a step of;
step two, adding the 2,4, 6-trimethyl benzyl chloride solution obtained in the step one into a high-pressure reaction kettle, adding 25g of an acid binding agent, 1.2g of a palladium catalyst and 2g of a phosphine ligand, and introducing CO for three times after nitrogen replacement; 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, a step of; the palladium catalyst is Pd (PPh) 3 ) 4 And 5% Pd/C, the Pd (PPh) 3 ) 4 And 5% Pd/C in an amount of 1:2; the phosphine ligands are dppf, dppp, dppb and dppe, and the mass ratio of dppf, dppp, dppb to dppe is 1:2:2:1, a step of;
continuously introducing CO, and carrying out carbonylation reaction under the condition that the CO pressure is 3.5Mpa and the temperature is 130 ℃ until the mass percent of 2,4, 6-trimethyl chlorobenzyl in the system is less than or equal to 1%, stopping the reaction, wherein the carbonylation reaction time 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, regulating the pH of the water phase to 2-3 by using a hydrochloric acid solution, and separating out a product to obtain the 2,4, 6-trimethylphenylacetic acid.
The yield of 2,4, 6-trimethylphenylacetic acid obtained in this example was 95.5% and the purity was 98.9%.
Example 11
The embodiment provides a preparation method of 2,4, 6-trimethylphenylacetic acid, which comprises the following steps:
step one, 100g of 2,4, 6-trimethyl benzyl chloride is dissolved in 600mL of solvent to obtain 2,4, 6-trimethyl benzyl chloride solution; the solvent comprises 450mL of water and 150mL of organic solvent, wherein the organic solvent is acetonitrile, dichloromethane, 1, 2-dichloroethane, benzene and toluene, and the mass ratio of the acetonitrile, the dichloromethane, the 1, 2-dichloroethane, the benzene and the toluene is 1:2:1:1:2;
step two, adding the 2,4, 6-trimethyl benzyl chloride solution obtained in the step one into a high-pressure reaction kettle, and then adding 26g of acid binding agent, 0.5g of palladium catalyst and 1g of phosphine ligand and nitrogenIntroducing CO for three times after replacement; 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 PdCl 2 (PhCN) 2 、PdCl 2 And Pd (OAc) 2 The PdCl 2 (PhCN) 2 、PdCl 2 And Pd (OAc) 2 The ratio of the amounts of the substances is 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, a step of;
continuously introducing CO, and carrying out carbonylation reaction under the condition that the CO pressure is 3.2Mpa and the temperature is 150 ℃ until the mass percent of 2,4, 6-trimethyl chlorobenzyl in the system is less than or equal to 1%, stopping the reaction, wherein the carbonylation reaction time 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, regulating the pH of the water phase to 2-3 by using a hydrochloric acid solution, and separating out a product to obtain the 2,4, 6-trimethylphenylacetic acid.
The yield of 2,4, 6-trimethylphenylacetic acid obtained in this example was 90.6% and the purity was 98.2%.
Example 12
The embodiment provides a preparation method of 2,4, 6-trimethylphenylacetic acid, which comprises the following steps:
step one, 100g of 2,4, 6-trimethyl benzyl chloride is dissolved in 600mL of solvent to obtain 2,4, 6-trimethyl benzyl chloride solution; the solvent comprises 500mL of water and 200mL of organic solvent, wherein the organic solvent is isopropanol, tertiary butanol and 2-methyltetrahydrofuran, and the mass ratio of the isopropanol to the tertiary butanol to the 2-methyltetrahydrofuran is 1:2:1, a step of;
step two, adding the 2,4, 6-trimethyl benzyl chloride solution obtained in the step one into a high-pressure reaction kettle, adding 90g of acid binding agent, 0.3g of palladium catalyst and 2g of phosphine ligand, and introducing CO for three times after nitrogen replacement; the acid binding agent is calcium hydroxide; the palladium catalyst is PdCl 2 And Pd (OAc) 2 The PdCl 2 And Pd (OAc) 2 The ratio of the amounts of the substances is 1:1, a step of; the phosphine ligand isBinap；
Continuously introducing CO, and carrying out carbonylation reaction under the condition that the CO pressure is 3.5Mpa and the temperature is 140 ℃ until the mass percent of 2,4, 6-trimethyl chlorobenzyl in the system is less than or equal to 1%, stopping the reaction, wherein 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, regulating the pH of the water phase to 2-3 by using a hydrochloric acid solution, and separating out a product to obtain the 2,4, 6-trimethylphenylacetic acid.
The yield of 2,4, 6-trimethylphenylacetic acid obtained in this example was 94.6% and the purity was 98.7%.
The foregoing description is only a preferred embodiment of the present invention, and is not intended to limit the present invention, and any simple modification, variation and equivalent structural changes of the above embodiment according to the technical matter of the present invention still fall within the scope of the technical solution of the present invention.
Claims (6)
1. A method for preparing 2,4, 6-trimethylphenylacetic acid, comprising the steps of:
step one, dissolving 2,4, 6-trimethyl benzyl chloride in a solvent to obtain a 2,4, 6-trimethyl benzyl chloride solution;
step two, adding the 2,4, 6-trimethyl benzyl chloride solution obtained in the step one into a high-pressure reaction kettle, adding an acid binding agent, a palladium catalyst and a phosphine ligand, and introducing CO after nitrogen replacement; in the second step, the mass of the palladium catalyst is 0.1% -1.5% of the mass of the 2,4, 6-trimethyl benzyl chloride, and the palladium catalyst comprises PdCl 2 (PPh 3 ) 2 、PdCl 2 (dppf) 2 、PdCl 2 (PhCN) 2 、PdCl 2 、Pd（OAc) 2 、Pd（PPh 3 ) 4 And one or more of Pd/C; in the second step, the mass of the phosphine ligand is 1% -3% of the mass of 2,4, 6-trimethylchlorobenzyl chloride, and the phosphine ligand comprises PPh 3 One or more of dppf, dppp, dppb, dppe, xantphos and Binap;
continuously introducing CO, and performing carbonylation reaction under the condition that the CO pressure is 0.5-3.5 mpa and the temperature is 60-150 ℃;
and step four, filtering, layering and adjusting acid in water phase of the system after the reaction in the step three 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 4.5-7 times of the mass of 2,4, 6-trimethylchlorobenzyl chloride, the volume of the solvent is in mL, and the mass of 2,4, 6-trimethylchlorobenzyl chloride is in 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 2-3 times of the volume 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 preparation method of 2,4, 6-trimethylphenylacetic acid according to claim 1, wherein in the second step, the molar weight of the acid binding agent is 0.3-2 times of the molar weight 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 third step, the reaction time of the carbonylation reaction is 6h to 12h.
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| 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 |
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| 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 |
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