CN110003023B - Preparation method of environment-friendly N, N-dimethylformamide dimethyl acetal - Google Patents
Preparation method of environment-friendly N, N-dimethylformamide dimethyl acetal Download PDFInfo
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- CN110003023B CN110003023B CN201910334933.7A CN201910334933A CN110003023B CN 110003023 B CN110003023 B CN 110003023B CN 201910334933 A CN201910334933 A CN 201910334933A CN 110003023 B CN110003023 B CN 110003023B
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- dimethyl acetal
- dimethylformamide dimethyl
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/48—Preparation of compounds having groups
- C07C41/50—Preparation of compounds having groups by reactions producing groups
Abstract
The invention relates to the field of organic synthesis, in particular to an environment-friendly preparation method of N, N-dimethylformamide dimethyl acetal, which comprises the following steps: generating dimethoxychloromethane by sodium methoxide and chloroform under the action of a catalyst; and (3) reacting the dimethoxychloromethane obtained in the step with dimethylamine to obtain N, N-dimethylformamide dimethyl acetal. The invention has the advantages that: the use of highly toxic dimethyl sulfate is avoided; the sodium chloride generated by the reaction can be used as a byproduct for sale after simple treatment, so that the generation amount of solid waste can be reduced, and the economic benefit of the product can be increased.
Description
Technical Field
The invention relates to the field of organic synthesis, in particular to a preparation method of an important intermediate N, N-dimethylformamide dialdehyde in organic synthesis.
Background
The N, N-dimethylformamide dimethyl acetal has wide application, can be used for synthesizing zaleplon, imatinib mesylate and other medicaments, is a condensing agent in the synthesis of high-grade pesticides, has good esterification and dehydration effects in organic synthesis, and has wide application as a methylation reagent. The N, N-dimethylformamide dimethyl acetal in the current market has more and wider requirements.
In Shandong chemical industry, 2003, preparation of N, N-dimethylformamide dimethyl acetal, dimethyl sulfate and N, N-Dimethylformamide (DMF) are reacted to form an imine complex, and the imine complex is reacted with sodium methoxide to obtain DMFA with a yield of 40-70%. The reaction formula is as follows:
the fine chemical intermediate 2008, 38, No. 5, optimization of the preparation process of dimethylformamide dimethyl acetal, improves the preparation process of dimethylformamide dimethyl acetal, and the optimized synthesis conditions are as follows: n (sodium methoxide): and (3) dropwise adding the imine complex at the temperature of-1.2: 1 and-5 ℃ for 2h, reacting at the temperature of-5 ℃ for 2h, and under the condition, increasing the yield from 40-70% to 76-80%.
The CN106083611A also adopts the reaction route, and uses a high-boiling point solvent to replace low-boiling point petroleum ether, so that the reaction temperature is increased from-5 to 0 ℃ to 20 to 30 ℃, the reaction conditions are milder, side reactions are reduced, and the yield is improved.
The 'Henan science' 35 nd 2 nd article 'a mild synthesis method of N, N-dimethylformamide dimethyl acetal' discloses that a novel organic solvent is used for replacing petroleum ether, in the solvent, an imine complex and sodium methoxide react at normal temperature (20-30 ℃), refrigeration equipment and a process under temperature conditions are not required, and industrial large-scale production is facilitated.
The preparation method uses highly toxic dimethyl sulfate as a raw material and generates a large amount of waste sodium methyl sulfate, which is not environment-friendly.
Disclosure of Invention
The technical problem to be solved by the invention is as follows: provides an environment-friendly preparation method of N, N-dimethylformamide dimethyl acetal.
In order to solve the technical problems, the invention provides the following technical scheme:
an environment-friendly preparation method of N, N-dimethylformamide dimethyl acetal comprises the following steps:
(1) generating dimethoxychloromethane by sodium methoxide and chloroform under the action of a catalyst;
(2) reacting the dimethoxychloromethane obtained in the step (1) with dimethylamine to obtain N, N-dimethylformamide dimethyl acetal;
the specific reaction formula is as follows:
preferably, the molar ratio of chloroform to sodium methoxide in the step (1) is 1: 2 to 3.
Preferably, the molar ratio of chloroform to dimethylamine is 1: 2-3; further, the molar ratio of chloroform to dimethylamine is 1: 2 to 2.1.
Preferably, the reaction solvent in step (1) is a mixture of methanol and other solvents; the other solvents comprise kerosene, dearomatized solvent oil and/or liquid paraffin oil, wherein the weight of the methanol accounts for 5-50% of the proportion of the total solvent; furthermore, the weight of the methanol accounts for 10 to 25 percent of the total proportion of the solvent.
Preferably, the total solvent amount is 1.5-4 times of the weight of the chloroform; furthermore, the total solvent amount is 2-3 times of the weight of the chloroform.
Preferably, the catalyst in the step (1) is selected from cuprous chloride, cuprous bromide or cuprous iodide; the dosage of the catalyst is 0.1-10% of the weight of the chloroform; furthermore, the dosage of the catalyst is 0.5 to 5 percent of the weight of the chloroform.
Preferably, the method further comprises the step of removing the generated sodium chloride and the catalyst after the reaction in the step (1) is completed; further, the removal of the sodium chloride formed and the catalyst is accomplished by means of pressure filtration.
Preferably, the step (2) is carried out by directly introducing dimethylamine into the filtrate obtained after filter pressing in the step (1).
Preferably, the raw material in the step (1) further comprises a phase transfer catalyst, and the catalyst can be used for fully contacting chloroform and sodium methoxide, so that the reaction time is shortened, and the product yield is improved. Specifically, the phase transfer catalyst includes quaternary ammonium salts such as: tetrabutylammonium chloride, tetrabutylammonium bromide; polyethers such as PEG200, PEG400, PEG600, and the like; cyclic crown ethers: 18-crown-6, 15-crown-5, and the like.
The invention has the advantages that: the use of highly toxic dimethyl sulfate is avoided; the sodium chloride generated by the reaction can be used as a byproduct for sale after simple treatment, so that the generation amount of solid waste can be reduced, and the economic benefit of the product can be increased.
Detailed Description
The invention is illustrated but not limited by the following examples. The technical solutions protected by the present invention are all the simple replacements or modifications made by the skilled person in the art.
Example 1
Adding 119 g (1mol) of chloroform and 113.4 g (2.1mol) of sodium methoxide, 25 g of methanol, 213 g of kerosene, 0.6 g of cuprous chloride as a catalyst and 0.2 g of tetrabutylammonium chloride into a 1L reactor, closing the reactor, starting heating, heating to about 80 ℃ for reaction for 2 hours, slowly heating to about 120 ℃ for reaction for 2.5 hours, cooling to below 30 ℃, performing pressure filtration, adding filtrate into the reactor, introducing 90 g (2mol) of dimethylamine, closing the reactor, starting heating to 140-150 ℃, performing heat preservation reaction for 2 hours, cooling to below 30 ℃, sampling, performing gas phase detection, and deducting a solvent peak: the purity of the product is 90.5 percent, the chloroform is 5.5 percent, and the trimethyl orthoformate is 2.1 percent. The obtained reaction liquid is rectified under normal pressure, and N, N-dimethylformamide dimethyl acetal products are collected to obtain 96.3 g, the purity is 98.1 percent, and the yield is 80.9 percent.
Example 2
Putting 178.5 g (1.5mol) of chloroform and 162 g (3mol) of sodium methoxide, 80 g of methanol, 455 g of kerosene, 3 g of cuprous bromide as a catalyst and 0.5 g of tetrabutylammonium bromide into a 2L reactor, closing the reactor, starting heating, heating to about 80 ℃ for reaction for 2 hours, slowly heating to about 120 ℃ for reaction for 3 hours, cooling to 28 ℃, performing pressure filtration, putting the filtrate into the reactor, introducing 180 g (4mol) of dimethylamine, closing the reactor, starting heating to 140-: the product purity was 93.5%, chloroform 3.5%, trimethyl orthoformate 1.9%. The obtained reaction liquid is rectified under normal pressure, and the N, N-dimethylformamide dimethyl acetal products are collected and collected to obtain 150 g, the purity is 98.4 percent, and the yield is 84 percent.
Example 3
The preparation method of N, N-dimethylformamide dimethyl acetal is the same as that in example 2, except that the solvent used in this example is a mixed solvent of 80 g of methanol and 455 g of dearomatized solvent oil, and 152 g of N, N-dimethylformamide dimethyl acetal is obtained, the purity is 98.3%, and the yield is 85.2%.
Example 4
The preparation method of N, N-dimethylformamide dimethyl acetal is the same as that in example 2, except that 80 g of methanol and 455 g of liquid paraffin oil are used as solvents in this example, 146 g of N, N-dimethylformamide dimethyl acetal is obtained with 98.5% purity and 81.8% yield.
Example 5
The preparation method of N, N-dimethylformamide dimethyl acetal is the same as that in example 2, except that 3.5 g of cuprous iodide and 0.5 g of tetrabutylammonium bromide are used as catalysts in this example. 155 g of N, N-dimethylformamide dimethyl acetal are obtained, the purity is 98.4% and the yield is 86.8%.
Example 6
The preparation method of N, N-dimethylformamide dimethyl acetal is the same as that in example 2, except that 130 g of methanol and 405 g of kerosene are used as solvents in this example, and 146 g of N, N-dimethylformamide dimethyl acetal is obtained, the purity is 98.3%, and the yield is 81.8%.
Example 7
The preparation method of N, N-dimethylformamide dimethyl acetal is the same as that in example 2, except that PEG400 is used as the phase transfer catalyst in this example, and the charge amount is 0.8 g, 145 g of N, N-dimethylformamide dimethyl acetal is obtained, the purity is 98.2%, and the yield is 81.2%.
Example 8
The preparation method of N, N-dimethylformamide dimethyl acetal is the same as that in example 2, except that the phase transfer catalyst used in this example is PEG600, the charge amount is 1 g, 147 g of N, N-dimethylformamide dimethyl acetal is obtained, the purity is 98.1%, and the yield is 82.4%.
Example 9
The preparation method of N, N-dimethylformamide dimethyl acetal is the same as that in example 2, except that the phase transfer catalyst used in this example is 18 crown 6, the charge amount is 1 g, 143 g of N, N-dimethylformamide dimethyl acetal is obtained, the purity is 98.2%, and the yield is 80.1%.
Example 10 (comparison with example 1)
Adding 119 g (1mol) of chloroform and 108 g (2mol) of sodium methoxide, 25 g of methanol, 213 g of kerosene and 0.6 g of cuprous chloride serving as a catalyst into a 1L reactor, closing the reactor, starting heating, heating to about 80 ℃ for reaction for 2 hours, slowly heating to about 120 ℃ for reaction for 2.5 hours, cooling to below 30 ℃, sampling, detecting that about 50% of chloroform remains unconverted, heating for continuously keeping the temperature for 5 hours, sampling and detecting, remaining about 15% of chloroform, performing filter pressing, adding filtrate into the reactor, introducing 90 g (2mol) of dimethylamine, closing the reactor, starting heating to 140-150 ℃, keeping the temperature for reaction for 2 hours, cooling to below 30 ℃, sampling gas phase detection, and deducting a solvent peak: the purity of the product is 70.5 percent, the chloroform is 15 percent, and the trimethyl orthoformate is 10 percent. The obtained reaction liquid is rectified under normal pressure, and the N, N-dimethylformamide dimethyl acetal product is collected to obtain 77.9 g, the purity is 95 percent, and the yield is 65.4 percent.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various changes and modifications can be made without departing from the inventive concept of the present invention, and these changes and modifications are all within the scope of the present invention.
Claims (10)
1. A preparation method of N, N-dimethylformamide dimethyl acetal is characterized by comprising the following steps:
(1) generating dimethoxychloromethane by sodium methoxide and chloroform under the action of a catalyst; the catalyst is selected from cuprous chloride, cuprous bromide or cuprous iodide;
(2) reacting the dimethoxychloromethane obtained in the step (1) with dimethylamine to obtain N, N-dimethylformamide dimethyl acetal;
a phase transfer catalyst is also added in the step (1), and the phase transfer catalyst is selected from tetrabutylammonium chloride, tetrabutylammonium bromide, PEG200, PEG400, PEG600, 18-crown-6 or 15-crown-5;
the specific reaction formula is as follows:
2. the process for producing N, N-dimethylformamide dimethyl acetal according to claim 1, wherein the molar ratio of chloroform to sodium methoxide in the step (1) is 1: 2 to 3.
3. The process for the preparation of N, N-dimethylformamide dimethyl acetal according to claim 1, wherein the molar ratio of chloroform to dimethylamine is 1: 2 to 3.
4. The process for producing N, N-dimethylformamide dimethyl acetal according to claim 1, wherein the reaction solvent in the step (1) is a mixture of methanol and another solvent; the other solvent is selected from kerosene, dearomatization solvent oil or liquid paraffin oil, wherein the weight of the methanol accounts for 5-50% of the proportion of the total solvent.
5. The method according to claim 4, wherein the total amount of the solvent used in the reaction is 1.5 to 4 times the weight of chloroform.
6. The method according to claim 5, wherein the total solvent amount is 2 to 3 times the weight of chloroform.
7. The process for producing N, N-dimethylformamide dimethyl acetal as claimed in claim 1, wherein the amount of the catalyst used in the step (1) is 0.1% to 10% by weight based on the weight of chloroform.
8. The process for producing N, N-dimethylformamide dimethyl acetal according to claim 1, wherein the reaction in the step (1) is completed, and further comprising a step of removing sodium chloride formed and the catalyst.
9. The process for producing N, N-dimethylformamide dimethyl acetal as claimed in claim 8, wherein the removal of sodium chloride and the catalyst formed in the step (1) is carried out by pressure filtration.
10. The process for producing N, N-dimethylformamide dimethyl acetal according to claim 9, wherein the step (2) is carried out by directly introducing dimethylamine into the filtrate obtained by the pressure filtration in the step (1).
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101747213A (en) * | 2008-12-19 | 2010-06-23 | 中国科学院兰州化学物理研究所 | Ionic liquid taking diether quaternary ammonium as cation and synthetic method thereof |
| CN104860848A (en) * | 2015-05-29 | 2015-08-26 | 盐城凯利药业有限公司 | Synthesis method of N-cyanoimido bis carbonate |
| CN106083611A (en) * | 2016-07-26 | 2016-11-09 | 河南省化工研究所有限责任公司 | A kind of synthetic method of N, N Dimethylformamide dimethyl acetal |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101747213A (en) * | 2008-12-19 | 2010-06-23 | 中国科学院兰州化学物理研究所 | Ionic liquid taking diether quaternary ammonium as cation and synthetic method thereof |
| CN104860848A (en) * | 2015-05-29 | 2015-08-26 | 盐城凯利药业有限公司 | Synthesis method of N-cyanoimido bis carbonate |
| CN106083611A (en) * | 2016-07-26 | 2016-11-09 | 河南省化工研究所有限责任公司 | A kind of synthetic method of N, N Dimethylformamide dimethyl acetal |
Non-Patent Citations (2)
| Title |
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| N,N-二甲基甲酰胺二甲基缩醛制备工艺优化;潘毅等;《精细化工中间体》;20081031;第38卷(第5期);第25-26,29页 * |
| N,N-二甲基甲酰胺二甲基缩醛的制备;张海峰等;《化学试剂》;19901231;第12卷(第2期);第125,124页 * |
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