CN110003023A - A kind of environmental-friendly N,N-dimethylformamide dimethylacetal preparation method - Google Patents
A kind of environmental-friendly N,N-dimethylformamide dimethylacetal preparation method Download PDFInfo
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- CN110003023A CN110003023A CN201910334933.7A CN201910334933A CN110003023A CN 110003023 A CN110003023 A CN 110003023A CN 201910334933 A CN201910334933 A CN 201910334933A CN 110003023 A CN110003023 A CN 110003023A
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- dimethylformamide dimethylacetal
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- chloroform
- dimethylamine
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- 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
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- 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
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Abstract
The present invention relates to organic synthesis fields, more particularly to a kind of environmental-friendly n,N-Dimethylformamide dimethylacetal preparation method, include the following steps: that sodium methoxide and chloroform generate dimethoxy chloromethanes under the action of catalyst；The dimethoxy chloromethanes that above-mentioned steps obtain reacts to obtain N,N-dimethylformamide dimethylacetal with dimethylamine.The invention has the advantages that: avoid the dimethyl suflfate using severe toxicity；The sodium chloride that reaction generates can be used as selling outside byproduct by simple process, can not only reduce the yield of solid waste, but also can increase the economic benefit of product.
Description
Technical field
The present invention relates to important intermediate N, N- dimethyl formyls in organic synthesis field more particularly to a kind of organic synthesis
The preparation method of amine dimethylacetal.
Background technique
N,N-Dimethylformamide dimethylacetal is widely used, can be used for synthesizing Zaleplon, imatinib mesylate etc.
Drug, while being the condensing agent in advanced pesticide synthesis, in addition it has good esterification dehydration in organic synthesis, makees
Have for methylating reagent and is widely applied.Existing market is more for the demand of N,N-dimethylformamide dimethylacetal, relatively wide.
" Shandong chemical industry " 01 phase in 2003, " preparation of n,N-Dimethylformamide dimethylacetal " is using by dimethyl suflfate
It reacts to form imino-complex with n,N-Dimethylformamide (DMF), then reacts to obtain DMFA with sodium methoxide, yield 40%~
70%.Reaction equation is as follows:
" fine-chemical intermediate " the 5th phases " dimethylformamide dimethyl acetal optimum preparation condition " of volume 38 in 2008,
Improve the preparation process of dimethylformamide dimethyl acetal, optimum synthesis condition are as follows: n (sodium methoxide): n (dimethyl suflfate)
=1.2:1, -5~5 DEG C of dropwise addition imino-complexes, time for adding 2h, -5~5 DEG C of reaction 2h, with this condition, yield is by 40%
~70% improves to 76%~80%.
Also above-mentioned reaction route is used in CN106083611A, replaces low-boiling petroleum ether with high boiling solvent, is made anti-
Temperature is answered to be increased to 20~30 DEG C from -5~0 DEG C, reaction condition is milder, reduces side reaction, improves yield.
A kind of " Henan science " the 2nd phase article " mild synthetic method of N,N-dimethylformamide dimethylacetal " of volume 35
It discloses and replaces petroleum ether using novel organic solvent, under the solvent, imino-complex reacts at normal temperature (20 with sodium methoxide
~30 DEG C) it is reacted, it does not need to provide the refrigeration equipment and technique of temperature condition, is more conducive to realizing that industrialization is extensive
Production.
Method made above does raw material using the dimethyl suflfate of severe toxicity and generates a large amount of methyl sodium sulphate and gives up admittedly, right
Environment is unfriendly.
Summary of the invention
The technical problem to be solved by the present invention is providing a kind of environmental-friendly N,N-dimethylformamide dimethylacetal system
Preparation Method.
Technical solution provided by the invention is as follows to solve above-mentioned technical problem:
A kind of environmental-friendly n,N-Dimethylformamide dimethylacetal preparation method, includes the following steps:
(1) sodium methoxide and chloroform generate dimethoxy chloromethanes under the action of catalyst；
(2) the dimethoxy chloromethanes that step (1) obtains reacts to obtain the contracting of N,N-dimethylformamide diformazan with dimethylamine
Aldehyde；
Specific reaction equation is as follows:
Preferably, the molar ratio of chloroform and sodium methoxide is 1:2~3 in the step (1).
Preferably, the molar ratio of the chloroform and dimethylamine is 1:2~3；Further, the chloroform and dimethylamine rub
You are than being 1:2~2.1.
Preferably, the reaction dissolvent in the step (1) is the mixture of methanol and other solvents；Other described solvent packets
Kerosene, de- fragrant solvent naphtha and/or saxol are included, it is 5%~50% that wherein methanol weight, which accounts for the specific gravity of total solvent,；Further
, the specific gravity that methanol weight accounts for total solvent is 10%~25%.
Preferably, total solvent amount is 1.5~4 times of chloroform weight；Further, total solvent amount is the 2~3 of chloroform weight
Times.
Preferably, catalyst is selected from stannous chloride, cuprous bromide or cuprous iodide in the step (1)；The catalyst
Dosage be chloroform weight 0.1%~10%；Further, the dosage of the catalyst be chloroform weight 0.5%~
5%.
Preferably, the step (1) after the reaction was completed, further includes the steps that removing the sodium chloride and catalyst generated；Into
One step, the sodium chloride and catalyst for removing generation are completed by filters pressing mode.
Preferably, by the way of the filtrate that the step (2) is obtained after dimethylamine to be passed directly into step (1) filters pressing into
Row.
Preferably, the raw material in the step (1) further includes phase transfer catalyst, using this catalyst can make chloroform with
Sodium methoxide comes into full contact with, and so as to shorten the reaction time, improves product yield.Specifically, the phase transfer catalyst includes quaternary ammonium
Salt is such as: tetrabutylammonium chloride, tetrabutylammonium bromide；Polyethers such as PEG200, PEG400, PEG600 etc.；Cyclic crown ether class:
18- crown- 6,15- crown- 5 etc..
The invention has the advantages that: avoid the dimethyl suflfate using severe toxicity；The sodium chloride that reaction generates passes through simple process
It can be used as selling outside byproduct, can not only reduce the yield of solid waste, but also the economic benefit of product can be increased.
Specific embodiment
Illustrate the present invention below in conjunction with example, but does not limit the present invention.In the art, technical staff is the present invention
Simple replacement or improvement belong in the technical solution protected of the present invention.
Embodiment 1
119 grams of (1mol) chloroforms of investment and 113.4 grams of (2.1mol) sodium methoxides in 1L reactor, 25 grams of methanol, kerosene 213
Gram, 0.6 gram of catalyst stannous chloride, 0.2 gram of tetrabutylammonium chloride close reactor, open heating, are first warming up to 80 DEG C or so
Then reaction 2 hours is to slowly warm up to 120 DEG C or so and reacts 2.5 hours, is cooled to 30 DEG C hereinafter, filters pressing, filtrate put into instead again
It answers in device, is passed through 90 grams of dimethylamine (2mol), close reactor, unlatching is heated to 140~150 DEG C of insulation reactions 2 hours, cools down
30 DEG C are cooled to hereinafter, sampling vapor detection, deducts solvent peak: product purity 90.5%, chloroform 5.5%, trimethyl orthoformate
2.1%.Obtained reaction solution is subjected to atmospheric distillation, n,N-Dimethylformamide dimethylacetal product is collected and obtains 96.3 grams, it is pure
Degree 98.1%, yield 80.9%.
Embodiment 2
178.5 grams of (1.5mol) chloroforms of investment and 162 grams of (3mol) sodium methoxides in 2L reactor, 80 grams of methanol, kerosene 455
Gram, 3 grams of catalyst cuprous bromide, 0.5 gram of tetrabutylammonium bromide close reactor, open heating, are first warming up to 80 DEG C or so instead
It answers 2 hours, is then to slowly warm up to 120 DEG C or so and reacts 3 hours, be cooled to 28 DEG C, filters pressing, filtrate puts into reactor again,
180 grams of dimethylamine (4mol) are passed through, reactor is closed, unlatching is heated to 140-150 DEG C of insulation reaction 2 hours, and cooling is cooled to
30 DEG C hereinafter, sampling vapor detection, deducts solvent peak: product purity 93.5%, chloroform 3.5%, trimethyl orthoformate 1.9%.
Obtained reaction solution is subjected to atmospheric distillation, n,N-Dimethylformamide dimethylacetal product is collected and obtains 150 grams, purity
98.4%, yield 84%.
Embodiment 3
The preparation method of n,N-Dimethylformamide dimethylacetal with embodiment 2, the difference is that, institute in the present embodiment
It is the mixed solvent of 80 grams of methanol and de- fragrant 455 grams of compositions of solvent naphtha with solvent, obtains n,N-Dimethylformamide dimethylacetal
152 grams, purity 98.3%, yield 85.2%.
Embodiment 4
The preparation method of n,N-Dimethylformamide dimethylacetal with embodiment 2, the difference is that, institute in the present embodiment
It is 80 grams and 455 grams of saxol of methanol with solvent, obtains 146 grams of n,N-Dimethylformamide dimethylacetal, purity
98.5%, yield 81.8%.
Embodiment 5
The preparation method of n,N-Dimethylformamide dimethylacetal with embodiment 2, the difference is that, used in the present embodiment
Catalyst is 3.5 grams of cuprous iodide, 0.5 gram of tetrabutylammonium bromide.Obtain 155 grams of n,N-Dimethylformamide dimethylacetal, it is pure
Degree 98.4%, yield 86.8%.
Embodiment 6
The preparation method of n,N-Dimethylformamide dimethylacetal with embodiment 2, the difference is that, institute in the present embodiment
It is 130 grams and 405 grams of kerosene of methanol with solvent, obtains 146 grams of n,N-Dimethylformamide dimethylacetal, purity 98.3% is received
Rate 81.8%.
Embodiment 7
The preparation method of n,N-Dimethylformamide dimethylacetal with embodiment 2, the difference is that, institute in the present embodiment
It is PEG400 with phase transfer catalyst, inventory is 0.8 gram, obtains 145 grams of n,N-Dimethylformamide dimethylacetal, purity
98.2%, yield 81.2%.
Embodiment 8
The preparation method of n,N-Dimethylformamide dimethylacetal with embodiment 2, the difference is that, institute in the present embodiment
It is PEG600 with phase transfer catalyst, inventory is 1 gram, obtains 147 grams of n,N-Dimethylformamide dimethylacetal, purity
98.1%, yield 82.4%.
Embodiment 9
The preparation method of n,N-Dimethylformamide dimethylacetal with embodiment 2, the difference is that, institute in the present embodiment
It is 18 hats 6 with phase transfer catalyst, inventory is 1 gram, obtains 143 grams of n,N-Dimethylformamide dimethylacetal, purity
98.2%, yield 80.1%.
Embodiment 10 (compares) with embodiment 1
119 grams of (1mol) chloroforms of investment and 108 grams of (2mol) sodium methoxides in 1L reactor, 25 grams of methanol, 213 grams of kerosene,
0.6 gram of catalyst stannous chloride, reactor is closed, opens heating, 80 DEG C or so is first warming up to and reacts 2 hours, then slowly rise
Temperature is reacted 2.5 hours to 120 DEG C or so, is cooled to 30 DEG C hereinafter, sample detection chloroform residue about 50% is unconverted at this time, heating
Continue to keep the temperature 5 hours sample detections, chloroform residue about 15%, filters pressing, filtrate puts into reactor again, is passed through 90 grams of dimethylamine
(2mol) closes reactor, and unlatching is heated to 140~150 DEG C of insulation reactions 2 hours, is cooled to 30 DEG C hereinafter, sampling gas
It mutually detects, deducts solvent peak: product purity 70.5%, chloroform 15%, trimethyl orthoformate 10%.Obtained reaction solution is carried out
Atmospheric distillation collects n,N-Dimethylformamide dimethylacetal product and obtains 77.9 grams, purity 95%, yield 65.4%.
What has been described above is only a preferred embodiment of the present invention, it is noted that for those of ordinary skill in the art
For, without departing from the concept of the premise of the invention, various modifications and improvements can be made, these belong to the present invention
Protection scope.
Claims (10)
1. a kind of environmental-friendly n,N-Dimethylformamide dimethylacetal preparation method, it is characterised in that include the following steps:
(1) sodium methoxide and chloroform generate dimethoxy chloromethanes under the action of catalyst；
(2) the dimethoxy chloromethanes that step (1) obtains reacts to obtain N,N-dimethylformamide dimethylacetal with dimethylamine；
Specific reaction equation is as follows:
2. n,N-Dimethylformamide dimethylacetal preparation method as described in claim 1, which is characterized in that the step
(1) molar ratio of chloroform and sodium methoxide is 1:2~3 in.
3. n,N-Dimethylformamide dimethylacetal preparation method as described in claim 1, which is characterized in that the chloroform with
The molar ratio of dimethylamine is 1:2~3.
4. n,N-Dimethylformamide dimethylacetal preparation method as described in claim 1, which is characterized in that the step
(1) reaction dissolvent in is the mixture of methanol and other solvents；Other described solvents include kerosene, de- fragrant solvent naphtha and/or
Saxol, it is 5%~50% that wherein methanol weight, which accounts for the specific gravity of total solvent,.
5. n,N-Dimethylformamide dimethylacetal preparation method as described in claim 1, which is characterized in that in above-mentioned reaction
The total solvent amount used is 1.5~4 times of chloroform weight.
6. n,N-Dimethylformamide dimethylacetal preparation method as claimed in claim 5, which is characterized in that the total solvent
Amount is 2~3 times of chloroform weight.
7. n,N-Dimethylformamide dimethylacetal preparation method as described in claim 1, which is characterized in that the step
(1) catalyst is selected from stannous chloride, cuprous bromide or cuprous iodide in；The dosage of the catalyst is the 0.1% of chloroform weight
~10%.
8. n,N-Dimethylformamide dimethylacetal preparation method as described in claim 1, which is characterized in that the step
(1) after the reaction was completed, further include the steps that removing the sodium chloride and catalyst generated；Further, the sodium chloride of generation is removed
It with catalyst is completed by filters pressing mode.
9. n,N-Dimethylformamide dimethylacetal preparation method as described in claim 1, which is characterized in that the step
(2) it is carried out by the way of the filtrate obtained after dimethylamine to be passed directly into step (1) filters pressing.
10. n,N-Dimethylformamide dimethylacetal preparation method as described in any one of claims 1 to 9, which is characterized in that
Raw material in the step (1) further includes phase transfer catalyst, the phase transfer catalyst include quaternary ammonium salt such as: tetrabutyl chlorine
Change ammonium, tetrabutylammonium bromide；Polyethers such as PEG200, PEG400, PEG600 etc.；Cyclic crown ether class: 18- crown- 6,15- crown- 5.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111454231A (en) * | 2020-05-08 | 2020-07-28 | 苏州煜佳生物医药技术有限公司 | Method for synthesizing 2-amino-5-nitrothiazole |
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| 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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2019
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| 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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Cited By (1)
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|---|---|---|---|---|
| CN111454231A (en) * | 2020-05-08 | 2020-07-28 | 苏州煜佳生物医药技术有限公司 | Method for synthesizing 2-amino-5-nitrothiazole |
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