CN109438217A - A kind of preparation method of 2,2-dimethylbutyric acid - Google Patents
A kind of preparation method of 2,2-dimethylbutyric acid Download PDFInfo
- Publication number
- CN109438217A CN109438217A CN201811483197.3A CN201811483197A CN109438217A CN 109438217 A CN109438217 A CN 109438217A CN 201811483197 A CN201811483197 A CN 201811483197A CN 109438217 A CN109438217 A CN 109438217A
- Authority
- CN
- China
- Prior art keywords
- acid
- sulfuric acid
- preparation
- acid dimethyl
- reaction
- 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
- C07C51/16—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation
- C07C51/305—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation with sulfur or sulfur-containing compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/08—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses the preparation methods of one kind 2,2- acid dimethyl, belong to pharmaceutical-chemical intermediate preparation process field.Using isoamyl alcohol and formic acid as raw material, under catalytic amount effect of sulfuric acid, intermediate isoamyl formate is obtained, then generates 2,2- acid dimethyl with sulfuric acid reaction again.The preparation method simple process, sulfuric acid dosage is few, and then reduces corresponding waste sulfuric acid solution, is easy industrialized production.
Description
Technical field
The present invention relates to the preparation methods of alkyl carboxylic acid, the in particular to carbonation process of one kind 2,2- acid dimethyl, belong to
In pharmaceutical-chemical intermediate preparation process field.
Background technique
2,2- acid dimethyls are a kind of important basic chemical industry raw materials, and 2,2- dimethyl-butyrylchlorine is generated after chlorination,
It is the key intermediate of agricultural insecticide Envidor and blood lipid-lowering medicine Simvastatin.
Envidor be earliest Beyer Co., Ltd exploitation spirocyclic tetronic acid class insecticidal/acaricidal agent, have been used at present cotton, vegetable dish,
The pests such as aleyrodid and tetranychid are prevented and treated on the crops such as citrus, grape.It developed time-consuming more than ten years as Bayer Cropscience Co., Ltd
A completely new mechanism of action acaricide, killing mechanism is totally different from existing various acaricides.Envidor passes through inhibition
The intracorporal Fatty synthesis of acarid destroys the energetic supersession activity of acarid, final kill mite evil, is a kind of completely new, efficiently non-interior
Cross resistance problem is not present with other existing acaricides in absorption foliar treatment acaricide, equal to the different mite class of various crop
There are fine preventive effect and outstanding lasting effect, not only ovicidal but also killed young mite, is particularly suitable for preventing and treating and resistance is generated to existing acaricide has
Harmful mite class.
The blood lipid-lowering medicine for the Statins (statin) that Simvastatin is developed by United States Merck company, the medicine column name is in the world
Health organization essential drugs inventory belongs to one of basic medical treatment system indispensability drug.The product were in Initial Public Offering in 1988, and 1991
Obtain U.S. FDA approval December, the simvastatin (Zocor) of Merck in 2000 comes second place on global marketing list, has
The huge market demand.
Currently, the main production of 2,2- acid dimethyls includes following several:
Method one, oxo synthesis
Using iso-amylene and carbon monoxide as raw material, pass through reaction under high pressure in the presence of the catalyst such as boron trifluoride, hydrofluoric acid
It is made, the process requirement high-tension apparatus, and uses CO gas, there are certain risks.
Method two, Grignard Reagent synthetic method
Methyl-magnesium-bromide is prepared in tetrahydrofuran, butanone is added in the Grignard Reagent of preparation, is obtained 2- methyl -2-
Butanol is then passed through carbon monoxide, carries out carbonylation as catalyst using cuprous oxide and obtains 2,2- acid dimethyl.
Method three, isoamyl alcohol and Catalyzed by Formic Acid synthetic method
Isoamyl alcohol and formic acid react under sulfuric acid catalysis, and the producting proportion molar ratio of three kinds of raw materials is 1.0:1.2:7.0.It should
Processing disadvantages are to generate a large amount of Waste Sulfuric Acids, and production efficiency is low, higher cost.Reaction generates a large amount of dilute sulfuric acids due to containing a small amount of
Product and impurity can not recycle, and cause the adverse consequences such as the production cost increases, environmental pollution.
During real reaction, formic acid is instilled in the concentrated sulfuric acid, carbon monoxide and water are generated, with the carry out sulphur of reaction
The concentration of acid is lower and lower, and when sulfuric acid concentration is lower than 91%, reaction is not just gone down, it is therefore desirable to and a large amount of sulfuric acid make solvent,
And sulfuric acid needs to be diluted to 50-60% after completion of the reaction, generating a large amount of dilute sulfuric acids can not reuse.
Summary of the invention
The purpose of the present invention is being directed to the third technique the deficiencies in the prior art, it is big to solve Waste Sulfuric Acid amount in production process
Problem.In order to reduce the dosage of sulfuric acid, the scheme that the present invention uses is: using isoamyl alcohol and formic acid as raw material, in catalytic amount sulfuric acid
Under effect, intermediate isoamyl formate is obtained, then generates 2,2- acid dimethyl with sulfuric acid reaction again.The preparation method technique
Simply, sulfuric acid dosage is few, and the waste sulfuric acid solution of generation is few, is easy industrialized production.
The preparation method of one kind 2,2- acid dimethyl, which comprises the following steps:
1) isoamyl alcohol and formic acid are mixed, under sulfuric acid catalysis, obtains isoamyl formate after heating reaction；
2) isoamyl formate is added drop-wise in the concentrated sulfuric acid, obtains 2,2- acid dimethyl after heating reaction.
Further, in the above-mentioned technical solutions, it in step 1), after sulfuric acid is using being added dropwise or being added at one time, slowly rises
Temperature reaction.It is carried out under the preferred counterflow condition of temperature reaction.
Further, in the above-mentioned technical solutions, in step 1), isoamyl alcohol, formic acid and sulfuric acid mole ratio are 1.0:
1.0-1.8:0.01-0.1.It is preferred that isoamyl alcohol, formic acid and sulfuric acid mole ratio are 1.0:1.2-1.5:0.03-0.05.
Further, in the above-mentioned technical solutions, in step 2), reaction temperature is 40-80 DEG C.Preferable reaction temperature is
55-60℃。
Further, in the above-mentioned technical solutions, in step 2, the concentrated sulfuric acid and isoamyl formate molar ratio are 0.8-1.5:
1。
Further, in the above-mentioned technical solutions, in step 2, mixing speed is affected to reaction, with 200-400 turn/
It is divided into most preferably, preferably 200-300 revs/min.
Invention beneficial effect
For the present invention using isoamyl alcohol and formic acid under catalytic amount effect of sulfuric acid, heating reaction obtains intermediate formic acid isoamyl
Ester then generates 2,2- acid dimethyl with sulfuric acid reaction.The preparation method simple process, can be carried out continuously, effectively subtract
Lack sulfuric acid dosage, thus the waste sulfuric acid solution generated significantly reduces, and is easy industrialized production.
Specific embodiment
Embodiment 1
To equipped in condenser, mechanical stirring and thermometer boss 1L four-hole boiling flask, 440.8g isoamyl alcohol, 368.2g is added
Formic acid and the 22g concentrated sulfuric acid temperature rising reflux 5-6 hours, cool down, and layering, upper layer is oil reservoir 560g, separate stand-by after oil reservoir.
Separately take 1L four-hole boiling flask that sulfuric acid 500g is added, speed of agitator 200r/min is warming up to 55-60 DEG C, is slowly added dropwise
The oil reservoir separated is stated, after being added dropwise, stirs 0.5-1 hours, is cooled to room temperature, obtained reaction solution is added drop-wise to ice water and is mixed
It in object 200g, is kept for 0-5 DEG C of temperature, is layered after being added dropwise, sulfur waste acid layer is added methylene chloride 150g and is extracted twice, and is associated with
150g washing is added once in machine layer, and the organic layer concentrated solvent separated is evaporated under reduced pressure under the conditions of 110 DEG C/- 0.095Mpa, obtains
To 2,2- acid dimethyl 460g, yield 79.3%.
Embodiment 2
To equipped in condenser, mechanical stirring and thermometer boss 1L four-hole boiling flask, 352.5g isoamyl alcohol, 324.0g is added
The 15g concentrated sulfuric acid is added dropwise at room temperature, is added dropwise within 20 minutes latter temperature rising reflux 5-6 hours for formic acid, cools down, and layering, upper layer is oil reservoir
445g is separated stand-by after oil reservoir.
Separately take 1L four-hole boiling flask that sulfuric acid 400g is added, speed of agitator 200r/min is warming up to 45-50 DEG C, is slowly added dropwise
The oil reservoir separated is stated, after being added dropwise, stirs 0.5-1 hours, is cooled to room temperature, obtained reaction solution is added drop-wise to ice water and is mixed
It in object 160g, is kept for 0-5 DEG C of temperature, is layered after being added dropwise, sulfur waste acid layer is added methylene chloride and is extracted twice, and merges organic
120g washing is added once in layer, and the organic layer concentrated solvent separated is evaporated under reduced pressure under the conditions of 110 DEG C/- 0.095Mpa, obtains
2,2- acid dimethyl 353g, yield 76.2%.
Embodiment 3
Into the 1L four-hole boiling flask equipped with condenser, mechanical stirring and thermometer boss, addition 396.0g isoamyl alcohol,
331.2g formic acid and the 20g concentrated sulfuric acid temperature rising reflux 5-6 hours, cool down, and layering, upper layer is oil reservoir 498g, separate after oil reservoir to
With.
Separately take 1L four-hole boiling flask that sulfuric acid 450g is added, speed of agitator 250r/min is warming up to 65~70 DEG C, is slowly added dropwise
The oil reservoir separated is stated, after being added dropwise, stirs 0.5-1 hours, is cooled to room temperature, obtained reaction solution is added drop-wise to ice water and is mixed
It in object, is kept for 0-5 DEG C of temperature, is layered after being added dropwise, sulfur waste acid layer is added methylene chloride and is extracted twice, and merges organic layer, adds
Enter 130g washing once, the organic layer concentrated solvent separated is evaporated under reduced pressure under the conditions of 110 DEG C/- 0.095Mpa, obtains 2,2-
Acid dimethyl 392.0g, yield 75.0%.
Embodiment 4
400 kilograms of isoamyl alcohol, 335 kilograms of formic acid and 20 kilograms of concentrated sulfuric acids are added in 1000L reaction kettle, are to slowly warm up to
It 90-100 DEG C, flows back 5-6 hours, cools down, layering, upper layer is 500 kilograms of oil reservoir.
The oil reservoir separated is slowly added into the 2000L reaction kettle equipped with 450 kilograms of concentrated sulfuric acids, reaction temperature be 65~
It 70 DEG C, after being added dropwise, stirs 0.5-1 hours, is cooled to room temperature, obtained reaction solution is added drop-wise in 180 kg of water, keep
It 0-5 DEG C of temperature, is layered after being added dropwise, sulfur waste acid layer is added methylene chloride and is extracted twice, and merges organic layer, is added 100 kilograms
Washing is primary, and the organic layer concentrated solvent separated is evaporated under reduced pressure under the conditions of 110 DEG C/- 0.095Mpa, obtains 2,2- dimethyl
407 kilograms of butyric acid, yield 78.0%.
Embodiment above describes basic principles and main features of the invention and advantages.The technical staff of the industry should
Understand, the present invention is not limited to the above embodiments, and the above embodiments and description only describe originals of the invention
Reason, under the range for not departing from the principle of the invention, various changes and improvements may be made to the invention, these changes and improvements are each fallen within
In the scope of protection of the invention.
Claims (8)
1. one kind 2, the preparation method of 2- acid dimethyl, which comprises the following steps:
1) isoamyl alcohol and formic acid are mixed, under sulfuric acid catalysis, obtains isoamyl formate after heating reaction；
2) isoamyl formate is added drop-wise in the concentrated sulfuric acid, obtains 2,2- acid dimethyl after heating reaction.
2. the preparation method of 2,2- acid dimethyl according to claim 1, it is characterised in that: in step 1), sulfuric acid is used
After being added dropwise or being added at one time, slow temperature rising reflux reaction.
3. the preparation method of 2,2- acid dimethyl according to claim 1, it is characterised in that: in step 1), isoamyl alcohol, first
Acid is 1.0:1.0-1.8:0.01-0.1 with sulfuric acid mole ratio.
4. the preparation method of 2,2- acid dimethyl according to claim 3, it is characterised in that: in step 1), isoamyl alcohol, first
Acid is 1.0:1.2-1.5:0.03-0.05 with sulfuric acid mole ratio.
5. the preparation method of 2,2- acid dimethyl according to claim 1, it is characterised in that: in step 2), reaction temperature
It is 40-80 DEG C.
6. the preparation method of 2,2- acid dimethyl according to claim 5, it is characterised in that: in step 2), reaction temperature
It is 55-60 DEG C.
7. the preparation method of 2,2- acid dimethyl according to claim 1, it is characterised in that: in step 2), the concentrated sulfuric acid with
Isoamyl formate molar ratio is 0.8-1.5:1.
8. the preparation method of 2,2- acid dimethyl according to claim 1, it is characterised in that: in step 2), mixing speed
It is 200-300 revs/min.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811483197.3A CN109438217B (en) | 2018-12-05 | 2018-12-05 | Preparation method of 2, 2-dimethylbutyric acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811483197.3A CN109438217B (en) | 2018-12-05 | 2018-12-05 | Preparation method of 2, 2-dimethylbutyric acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109438217A true CN109438217A (en) | 2019-03-08 |
| CN109438217B CN109438217B (en) | 2021-07-16 |
Family
ID=65557225
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811483197.3A Active CN109438217B (en) | 2018-12-05 | 2018-12-05 | Preparation method of 2, 2-dimethylbutyric acid |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109438217B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2136808A (en) * | 1983-03-21 | 1984-09-26 | Elf France | Process for preparing alpha-disubstituted monocarboxylic acids and esters |
-
2018
- 2018-12-05 CN CN201811483197.3A patent/CN109438217B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2136808A (en) * | 1983-03-21 | 1984-09-26 | Elf France | Process for preparing alpha-disubstituted monocarboxylic acids and esters |
Non-Patent Citations (1)
| Title |
|---|
| 丁成荣等: "2,2-二甲基丁酸的合成新方法", 《中国药物化学杂志》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109438217B (en) | 2021-07-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103626790A (en) | Liquid chelated calcium as well as preparation method and use thereof | |
| CN110028399B (en) | Preparation method of 2-methyl-4-chlorophenoxyacetic acid | |
| CN109438217A (en) | A kind of preparation method of 2,2-dimethylbutyric acid | |
| CN106397208A (en) | Preparation method of boscalid intermediate 2-(4-chlorophenyl)nitrobenzene | |
| CN100586923C (en) | Method for preparing phenylacetic acid by non-catalyzed hydrolysis of benzyl cyanide in near-critical water medium | |
| Snyder et al. | Polyphosphoric Acid as a Reagent in Organic Chemistry. VII. Acylation1 | |
| CN103588592B (en) | Method for preparing amino acid water-soluble fertilizer by nim leaves | |
| CN101041602A (en) | Dextroglucose plants organic nutrient solution and producing technique | |
| CN101906063A (en) | Scale synthesis process of procymidone original drug of efficient agricultural bactericide in two steps | |
| CN104628568A (en) | Method for producing bifenthrin with clean synthesizing process | |
| CN105218400A (en) | A kind of green production process of bromothalonil | |
| DE2619091C2 (en) | Continuous process for the epoxidation of organic compounds containing olefinic double bonds | |
| CN100352796C (en) | Process of preparing benzaldehyde through continuous hydrolysis of ammonia spirit catalytic of cinnamaldehyde in near critical water | |
| CN104628569A (en) | Method for producing bifenthrin with clean synthesizing process | |
| CN107746335A (en) | A kind of production method of the organic foliage fertilizer based on the antibacterial insecticidal action of Chinese medicine | |
| CN105153036A (en) | Method for preparing pyrazole through acrolein fixed bed reaction | |
| CN112674097A (en) | Chitosan oligosaccharide and S-abscisic acid compound sterilization regulator and preparation method thereof | |
| CN109369587A (en) | A kind of production technology of high-purity high-yield Envidor | |
| CN114195631B (en) | Preparation process of 3, 3-dimethylbutyric acid | |
| CN106946665A (en) | The method that phenols chemicals and acids chemicals are extracted from pyrolkigneous liquid | |
| CH378873A (en) | Process for the production of cyclohexanol and cyclohexanone | |
| CN111807991A (en) | Method for synthesizing 2-amino-2, 3-dimethylbutyronitrile by using microchannel reactor | |
| CN109627111A (en) | A kind of liquid compound organic fertilizer and preparation method thereof | |
| CN103497094A (en) | Preparation method of anisic aldehyde | |
| CN106590717A (en) | Method for hydrothermally preparing wood vinegar from biomass |
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 | ||
| CB03 | Change of inventor or designer information |
Inventor after: Sun Faming Inventor after: Jiang Dianbao Inventor after: Zhang Hongxue Inventor before: Sun Faming Inventor before: Jiang Dianping Inventor before: Zhang Hongxue |
|
| CB03 | Change of inventor or designer information | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |