CN114195631B

CN114195631B - Preparation process of 3, 3-dimethylbutyric acid

Info

Publication number: CN114195631B
Application number: CN202111568021.XA
Authority: CN
Inventors: 孙发明; 姜殿宝; 张洪学; 盖世杰; 武君
Original assignee: DALIAN QIKAI MEDICAL TECHNOLOGY CO LTD
Current assignee: DALIAN QIKAI MEDICAL TECHNOLOGY CO LTD
Priority date: 2021-12-20
Filing date: 2021-12-20
Publication date: 2024-03-29
Anticipated expiration: 2041-12-20
Also published as: CN114195631A

Abstract

The invention discloses an improved preparation process of 3, 3-dimethylbutyric acid, and belongs to the technical field of medical intermediates. The process method takes chloro-tert-butane and vinylidene chloride as raw materials, obtains an intermediate 1, 1-dichloro-3, 3-dimethylbutene under the catalysis of Lewis acid, then hydrolyzes in inorganic base and proton solvent, and finally obtains the 3, 3-dimethylbutyric acid by neutralization and distillation. The process does not produce waste sulfuric acid, and the produced neutral wastewater is easy to treat, thereby being beneficial to industrial production.

Description

Preparation process of 3, 3-dimethylbutyric acid

Technical Field

The invention relates to a fine chemical product, in particular to a preparation process of 3, 3-dimethylbutyric acid.

Background

3, 3-dimethylbutyric acid is an important basic chemical raw material, and the chloridized 3, 3-dimethylbutyryl chloride is an important intermediate of novel insecticidal and acaricidal spirodiclofen developed by Germany Bayer company.

Spirodiclofen is the earliest spirotetraonic acid insecticidal acaricide developed by Bayer company, the research of the Bayer on the spirotetronic acid compound starts in 1993, and when the company researches and synthesizes protoporphyrinogen oxidase (PPO) inhibitor herbicide with a multi-ring-allyl structure, the acaricide spirodiclofen which has the function of inhibiting acetyl coenzyme A carboxylase (ACCase) and integrates high activity and safety is finally discovered through a series of structural modifications. Through further structural optimization, the acaricide spiromesifen and the insecticide spirotetramat are discovered successively. The advent of spirodiclofen can be said to open up a new chapter for research on spirocyclic tetronic acid compounds by the pesticide industry. The insecticidal composition is used for preventing and controlling pests such as whitefly, spider mites and the like on crops such as cotton, vegetables, oranges, grapes and the like. As an acaricide with a brand new action mechanism developed by Bayer crop science companies for more than ten years, the acaricide has a mite killing mechanism which is completely different from the existing various acaricides. The spiromesifen is a brand-new and high-efficiency non-systemic foliar treatment acaricide which can destroy the energy metabolism activity of mites and finally kill the mites by inhibiting the synthesis of fat in mites, has no cross resistance problem with other existing acaricides, has good control effect and excellent lasting effect on different mites of various crops, kills eggs and kills young mites, and is particularly suitable for controlling harmful mites with resistance to the existing acaricides.

The main processes for producing 3, 3-dimethylbutyric acid at present are as follows: patent CN1778789A, CN101570477A, CN102249888A, US2004/0210094A1 adopts a method of condensing tertiary butanol and vinylidene chloride in a large amount of concentrated sulfuric acid, and then adding water for hydrolysis. The process is a main method for industrially producing 3, 3-dimethylbutyric acid at present, but sulfuric acid participates in the reaction, so that the sulfuric acid consumption is large, a large amount of brown acidic wastewater is generated after hydrolysis, and the treatment is difficult. Patent CN 111116348A provides an oxygen oxidation process of 3, 3-dimethylbutyraldehyde catalyzed by a bimetallic catalyst. The method has the advantages of difficult acquisition of raw materials and high industrialization cost.

Disclosure of Invention

The invention aims at solving the problems of large waste sulfuric acid amount and difficult recovery in the production process, aiming at the defects of the prior art for producing 3, 3-dimethylbutyric acid. Because sulfuric acid is used in the reaction process, water is needed to be added for hydrolysis after the reaction is finished, dilute sulfuric acid with the concentration of 40-60% is produced, the dilute sulfuric acid cannot be directly recycled, and the waste acid is dark in color and smell and is difficult to treat.

In order to replace sulfuric acid, the invention adopts the following scheme: the intermediate 1, 1-dichloro-3, 3-dimethylbutene is obtained by using tert-butyl chloride and vinylidene chloride as raw materials under the catalysis of Lewis acid. 1, 1-dichloro-3, 3-dimethylbutene is a halogenated olefin compound, the hydrolysis is difficult, the hydrolysis is carried out by adopting an inorganic strong base and high boiling point protonic solvent method in an optimized way, the reaction period is short, and the raw materials are completely reacted; the reaction equation is:

the preparation process of the 3, 3-dimethylbutyric acid comprises the following steps:

step A: uniformly mixing tert-butyl chloride and a catalyst, and dropwise adding vinylidene chloride for reaction; then the reaction solution is hydrolyzed and layered, and alkali is added into the organic layer; concentrating and recovering the solvent after drying to obtain an intermediate product 1, 1-dichloro-3, 3-dimethylbutene;

and (B) step (B): adding 1, 1-dichloro-3, 3-dimethylbutene into inorganic base and proton solvent for reaction; adding acid into the reaction solution, and extracting with an organic solvent; concentrating the extract, and rectifying under reduced pressure to obtain 3, 3-dimethylbutyric acid.

Further, in the above technical scheme, the catalyst in step a is a lewis acid catalyst selected from zinc chloride, ferric chloride, aluminum chloride, boron trifluoride or antimony pentachloride.

Further, in the technical scheme, the mass ratio of the chlorinated tertiary butane to the catalyst in the step A is 1.0:0.01 to 0.1; the mol ratio of the chloro-tert-butane to the vinylidene chloride is 1.0:1.0-1.5.

Further, in the above technical scheme, the reaction temperature in the step A is 0-40 ℃, preferably 10-30 ℃.

Further, in the above technical scheme, in the step a, adding alkali to the oil layer to adjust the reaction ph=6 to 9; in step B, the ph=1 to 3 is adjusted by adding acid.

Further, in the above technical scheme, the protic solvent in step B is ethylene glycol, glycerol or 1, 2-propylene glycol.

Further, in the above technical scheme, the inorganic base in step B is selected from sodium hydroxide or potassium hydroxide.

Further, in the technical scheme, the reaction temperature of the step B is 120-180 ℃; concentrating the extractive solution at normal pressure until no liquid flows at 110-130deg.C.

Further, in the above technical scheme, the organic solvent in the step B is selected from 1, 2-dichloroethane, dichloromethane or chloroform.

Detailed Description

Example 1

350g of methylene dichloride and 13.0g of ferric trichloride are added into a 1L four-neck flask provided with a condenser and a thermometer sleeve, the temperature is reduced to 0-10 ℃, 92.5g of tert-butyl chloride is slowly added, 106g of vinylidene chloride is dropwise added, the discharged gas is absorbed by alkali liquor, the temperature is kept for 1 hour after the dropwise addition, the temperature is slowly increased to 30-40 ℃, the content of the tert-butyl chloride is detected by sampling GC and is less than or equal to 0.5%, and the temperature is reduced to room temperature. Slowly adding 60g of water into the reaction kettle, fully stirring, standing for layering, adding 5% sodium carbonate solution into the organic layer at the lower layer to wash the organic layer until the pH value is 8-9, taking the organic layer, adding anhydrous magnesium sulfate, drying, and concentrating to recover dichloromethane. Concentrating the mother liquor at the temperature of 40-50 ℃, heating to 80 ℃ without flowing liquid, and then introducing an empty pump to pump out the residual solvent to obtain 135g of 1, 1-dichloro-3, 3-dimethylbutene, wherein the GC content is 95.2%, and the yield is 84%.

56.0g of potassium hydroxide is added into a 500mL four-neck flask, 68.5g of water is slowly added under stirring, 110g of 1, 2-propylene glycol is added, the temperature is raised to 140-150 ℃, 46.0g of 1, 1-dichloro-3, 3-dimethylbutene is obtained through one-step reaction, after the dripping is finished, stirring is carried out for 4-6 hours, the temperature is reduced to room temperature, 80g of water is added into the reaction liquid, 40g of hydrochloric acid is added dropwise to adjust the pH to be less than 3, 80g of 1, 2-dichloroethane is added for extraction twice, an organic layer is separated, 1, 2-dichloroethane is recovered through normal temperature concentration solvent, 26.8g of 3-dimethylbutyric acid is obtained through vacuum-0.098 MPa of a circulating water pump, and vacuum rectification is carried out at the oil temperature of 120-130 ℃ to obtain the 3, the GC content is 98.5%, and the yield is 77.0%.

Example 2

350g of methylene dichloride and 11.5g of zinc chloride are added into a 1L four-neck flask with a condenser and a thermometer sleeve for mechanical stirring, the temperature is reduced to 0-10 ℃, 92.5g of tert-butyl chloride is slowly added, 106g of vinylidene chloride is dropwise added, the discharged gas is absorbed by alkali liquor, the temperature is kept for 1 hour after the dropwise addition, the temperature is slowly increased to 30-40 ℃, the content of the tert-butyl chloride is detected by sampling GC and is less than or equal to 0.5%, and the temperature is reduced to room temperature. Slowly adding 60g of water into the reaction kettle, fully stirring, standing for layering, adding 5% sodium carbonate solution into the organic layer at the lower layer to wash the organic layer until the pH value is 8-9, taking the organic layer, adding anhydrous magnesium sulfate, drying, and concentrating to recover dichloromethane. Concentrating the mother liquor at the temperature of 40-50 ℃, heating to 80 ℃ without flowing liquid, and then introducing an empty pump to pump out the residual solvent to obtain 132g of 1, 1-dichloro-3, 3-dimethylbutene, wherein the GC content is 93.4%, and the yield is 80%.

Adding 56.0g of potassium hydroxide into a 500mL four-neck flask, slowly adding 68.5g of water under stirring, adding 110g of ethylene glycol, heating to 140-150 ℃, dropwise adding 46.0g of 1, 1-dichloro-3, 3-dimethylbutene for one-step reaction, stirring for 4-6 hours after the dropwise adding is finished, cooling to room temperature, adding 80g of water into the reaction solution, dropwise adding 40g of hydrochloric acid, adjusting the pH to be less than 3, adding 80g of 1, 2-dichloroethane, extracting twice, separating an organic layer, concentrating the solvent at normal temperature, recovering 1, 2-dichloroethane, vacuum-0.098 MPa by a circulating water pump, and performing reduced pressure rectification at the oil temperature of 120-130 ℃ to obtain 24.3g of 3-dimethylbutyric acid with the GC content of 98.2% and the yield of 70.0%.

Example 3

350g of methylene dichloride and 13.0g of ferric trichloride are added into a 1L four-neck flask provided with a condenser and a thermometer sleeve, the temperature is reduced to 0-10 ℃, 92.5g of tert-butyl chloride is slowly added, 106g of vinylidene chloride is dropwise added, the discharged gas is absorbed by alkali liquor, the temperature is kept for 1 hour after the dropwise addition, the temperature is slowly increased to 30-40 ℃, the content of the tert-butyl chloride is detected by sampling GC and is less than or equal to 0.5%, and the temperature is reduced to room temperature. Slowly adding 60g of water into the reaction kettle, fully stirring, standing for layering, adding 5% sodium carbonate solution into the organic layer at the lower layer to wash the organic layer until the pH value is 8-9, taking the organic layer, adding anhydrous magnesium sulfate, drying, and concentrating to recover dichloromethane. Concentrating the mother liquor at the temperature of 40-50 ℃, heating to 80 ℃ without flowing liquid, and then introducing an empty pump to pump out the residual solvent to obtain 125.5g of 1, 1-dichloro-3, 3-dimethylbutene with the GC content of 95.5% and the yield of 82%.

Adding 42.0g of sodium hydroxide into a 500mL four-neck flask, slowly adding 68.5g of water under stirring, adding 110g of 1, 2-propylene glycol, heating to 140-150 ℃, dropwise adding 46.0g of 1, 1-dichloro-3, 3-dimethylbutene for one-step reaction, stirring for 4-6 hours after the dropwise adding is finished, cooling to room temperature, adding 80g of water into the reaction solution, dropwise adding 40g of hydrochloric acid to adjust the pH to be less than 3, adding 80g of 1, 2-dichloroethane, extracting twice, separating an organic layer, concentrating the solvent at normal temperature to recover 1, 2-dichloroethane, vacuum-0.098 MPa by a circulating water pump, and performing vacuum distillation at the oil temperature of 120-130 ℃ to obtain 25.2g of 3, 3-dimethylbutyric acid, wherein the GC content is 98.9%, and the yield is 73.0%.

The foregoing is merely a preferred embodiment of the present invention, and it should be noted that the above-mentioned preferred embodiment should not be construed as limiting the invention, and the scope of the invention should be defined by the appended claims. It will be apparent to those skilled in the art that various modifications and adaptations can be made without departing from the spirit and scope of the invention, and such modifications and adaptations are intended to be comprehended within the scope of the invention.

Claims

1. The preparation process of the 3, 3-dimethylbutyric acid is characterized by comprising the following steps of:

adding 350g of methylene dichloride and 13.0g of ferric trichloride into a 1L four-neck flask provided with a condenser, mechanical stirring and a thermometer sleeve, cooling to 0-10 ℃, slowly adding 92.5g of tert-butyl chloride, dropwise adding 106g of vinylidene chloride, absorbing the discharged gas alkali liquor, preserving heat for 1 hour after the dropwise adding is finished, slowly heating to 30-40 ℃, sampling, detecting that the content of the tert-butyl chloride is less than or equal to 0.5% by GC, and cooling to room temperature; slowly adding 60g of water into the reaction kettle, fully stirring, standing for layering, adding 5% sodium carbonate solution into the organic layer at the lower layer to wash the organic layer until the pH value is 8-9, taking the organic layer, adding anhydrous magnesium sulfate, drying, concentrating and recovering dichloromethane; concentrating the mother liquor at 40-50 ℃, heating to 80 ℃ without flowing liquid, and then pumping the residual solvent by a vacuum pump to obtain 135g of 1, 1-dichloro-3, 3-dimethylbutene with the GC content of 95.2%;

56.0g of potassium hydroxide is added into a 500mL four-neck flask, 68.5g of water is slowly added under stirring, 110g of 1, 2-propylene glycol is added, the temperature is raised to 140-150 ℃, 46.0g of 1, 1-dichloro-3, 3-dimethylbutene is obtained through one-step reaction, after the dripping is finished, stirring is carried out for 4-6 hours, the temperature is reduced to room temperature, 80g of water is added into the reaction liquid, 40g of hydrochloric acid is added dropwise to adjust the pH to be less than 3, 80g of 1, 2-dichloroethane is added for extraction twice, an organic layer is separated, 1, 2-dichloroethane is recovered through normal temperature concentration solvent, 26.8g of 3, 3-dimethylbutyric acid is obtained through vacuum-0.098 MPa of a circulating water pump, and vacuum rectification is carried out at the oil temperature of 120-130 ℃ under the condition that the GC content is 98.5%.

2. The preparation process of the 3, 3-dimethylbutyric acid is characterized by comprising the following steps of:

adding 350g of methylene dichloride and 11.5g of zinc chloride into a 1L four-neck flask provided with a condenser, mechanical stirring and a thermometer sleeve, cooling to 0-10 ℃, slowly adding 92.5g of tert-butyl chloride, dropwise adding 106g of vinylidene chloride, absorbing the discharged gas alkali liquor, preserving heat for 1 hour after the dropwise adding is finished, slowly heating to 30-40 ℃, sampling, detecting that the content of the tert-butyl chloride is less than or equal to 0.5% by GC, and cooling to room temperature; slowly adding 60g of water into the reaction kettle, fully stirring, standing for layering, adding 5% sodium carbonate solution into the organic layer at the lower layer to wash the organic layer until the pH value is 8-9, taking the organic layer, adding anhydrous magnesium sulfate, drying, concentrating and recovering dichloromethane; concentrating the mother liquor at 40-50 ℃, heating to 80 ℃ without flowing liquid, and then pumping the residual solvent by a vacuum pump to obtain 132g of 1, 1-dichloro-3, 3-dimethylbutene with 93.4% GC content;

adding 56.0g of potassium hydroxide into a 500mL four-neck flask, slowly adding 68.5g of water under stirring, adding 110g of ethylene glycol, heating to 140-150 ℃, dropwise adding 46.0g of 1, 1-dichloro-3, 3-dimethylbutene for one-step reaction, stirring for 4-6 hours after the dropwise adding is finished, cooling to room temperature, adding 80g of water into the reaction solution, dropwise adding 40g of hydrochloric acid, adjusting the pH to be less than 3, adding 80g of 1, 2-dichloroethane, extracting twice, separating an organic layer, concentrating the solvent at normal temperature, recovering 1, 2-dichloroethane, vacuum-0.098 MPa by a circulating water pump, and performing reduced pressure rectification at the oil temperature of 120-130 ℃ to obtain 24.3g of 3-dimethylbutyric acid with the GC content of 98.2%.

3. The preparation process of the 3, 3-dimethylbutyric acid is characterized by comprising the following steps of:

350g of methylene dichloride and 13.0g of ferric trichloride are added into a 1L four-neck flask provided with a condenser, a mechanical stirring and a thermometer sleeve, the temperature is reduced to 0-10 ℃, 92.5g of tert-butyl chloride is slowly added, 106g of vinylidene chloride is dropwise added, the discharged gas alkali liquor is absorbed, the temperature is kept for 1 hour after the dropwise addition, the temperature is slowly increased to 30-40 ℃, the content of the tert-butyl chloride detected by sampling GC is less than or equal to 0.5%, and the temperature is reduced to room temperature. Slowly adding 60g of water into the reaction kettle, fully stirring, standing for layering, adding 5% sodium carbonate solution into the organic layer at the lower layer to wash the organic layer until the pH value is 8-9, taking the organic layer, adding anhydrous magnesium sulfate, drying, concentrating and recovering dichloromethane; concentrating the mother liquor at 40-50 ℃, heating to 80 ℃ without flowing liquid, and then introducing a vacuum pump to pump out residual solvent to obtain 125.5g of 1, 1-dichloro-3, 3-dimethylbutene with 95.5% GC content;