CN115772088A - Preparation method of tert-butoxy (bisdimethylamino) methane - Google Patents
Preparation method of tert-butoxy (bisdimethylamino) methane Download PDFInfo
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- CN115772088A CN115772088A CN202211693807.9A CN202211693807A CN115772088A CN 115772088 A CN115772088 A CN 115772088A CN 202211693807 A CN202211693807 A CN 202211693807A CN 115772088 A CN115772088 A CN 115772088A
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- Prior art keywords
- tert
- butoxy
- bisdimethylamino
- methane
- reaction
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- -1 tert-butoxy (bisdimethylamino) methane Chemical compound 0.000 title claims abstract description 22
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 39
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims abstract description 30
- 238000006243 chemical reaction Methods 0.000 claims abstract description 25
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims abstract description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims abstract description 22
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 18
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 claims abstract description 15
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims abstract description 14
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000010438 heat treatment Methods 0.000 claims abstract description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims abstract description 8
- 238000010992 reflux Methods 0.000 claims abstract description 6
- 239000000047 product Substances 0.000 claims description 8
- 238000005406 washing Methods 0.000 claims description 7
- 239000012065 filter cake Substances 0.000 claims description 5
- 239000000706 filtrate Substances 0.000 claims description 5
- 238000001914 filtration Methods 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 239000012295 chemical reaction liquid Substances 0.000 claims description 2
- 238000001816 cooling Methods 0.000 claims description 2
- 239000011541 reaction mixture Substances 0.000 claims 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- 230000015572 biosynthetic process Effects 0.000 abstract description 4
- 150000001875 compounds Chemical class 0.000 abstract description 3
- 238000009776 industrial production Methods 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 16
- 229910052757 nitrogen Inorganic materials 0.000 description 12
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 238000005086 pumping Methods 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- 229910021135 KPF6 Inorganic materials 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 125000005594 diketone group Chemical group 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- HXRAMSFGUAOAJR-UHFFFAOYSA-N n,n,n',n'-tetramethyl-1-[(2-methylpropan-2-yl)oxy]methanediamine Chemical compound CN(C)C(N(C)C)OC(C)(C)C HXRAMSFGUAOAJR-UHFFFAOYSA-N 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000007039 two-step reaction Methods 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of tert-butoxy (bisdimethylamino) methane, which relates to the technical field of compound synthesis and comprises the following steps: s11, adding dimethyl sulfate and DMF into a four-mouth bottle, heating to 60 ℃, and reacting for 4 hours; s12, dripping 2M tetrahydrofuran solution of dimethylamine, slightly releasing heat at the early stage, and adding toluene after dripping; s13, heating to 70 ℃, and carrying out reflux reaction for 1h; the reaction solution of S14 is cooled to room temperature, is kept stand for layering, and the lower layer is washed three times by methyl tert-butyl ether to obtain an intermediate, and the invention has the beneficial effects that: the method is characterized in that tetrahydrofuran solution of N, N-dimethylformamide, dimethyl sulfate and dimethylamine is used as raw materials, and ether solution of potassium tert-butoxide reacts with the intermediate prepared in the first step to prepare tert-butoxy (bisdimethylamino) methane, and the method is simple in process, mild in reaction conditions, high in safety and in accordance with green chemistry; the prepared tert-butoxy (bisdimethylamino) methane has high yield and high purity; the scheme has stronger economical practicability and accords with industrial production.
Description
Technical Field
The invention relates to the technical field of compound synthesis, in particular to a preparation method of tert-butoxy (bisdimethylamino) methane.
Background
Tert-butoxy (bisdimethylamino) methane, also known as Bredereck reagent, is an important intermediate in organic synthesis. For example, amination reaction for active methylene, methyl group, and organic reaction for oxidation of ketone to diketone.
The synthesis method for preparing tert-butoxy (bisdimethylamino) methane is divided into two steps. Firstly, preparing an intermediate compound of N, N, N ', N' -tetramethyl formamidine salt; and secondly, reacting potassium tert-butoxide with an intermediate to obtain a target product. In US patent US2017260189, it is proposed that A1, an intermediate obtained by reacting N, N-dimethylformamide, p-toluenesulfonyl chloride and KPF6 in an aqueous solution, is N, N' -tetramethylformamidine hexafluorophosphate, which is then reacted with a THF solution of potassium tert-butoxide to obtain the target product. The method has the disadvantages of high and low temperature change in the reaction process, nitrogen protection, relatively complex reaction conditions and difficult large-scale industrial production. Wasserman and Ives (Wasserman, H.H.; ives, J.L.J. org.chem.1985,50 (19), 3573-3580) followed by Bredereck's procedure, dropwise addition of N, N-dimethylformamide and dimethyl sulfate to a toluene solution of dimethylamine reacted to form the intermediate N, N, N ', N ' -tetramethylformamidine methyl sulfate, which was then reacted with a solution of potassium tert-butoxide in ether to give the desired product in 67% yield in the second step. The two-step reaction process of the scheme has mild conditions and simple operation method, but the yield is not high, and the method is not an advantage of industrial amplification production, so that a preparation method of tert-butoxy (bisdimethylamino) methane is provided.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides a preparation method of tert-butoxy (bisdimethylamino) methane, which solves the problems in the background technology.
In order to realize the purpose, the invention is realized by the following technical scheme: a preparation method of tert-butoxy (bisdimethylamino) methane comprises the following steps:
s11, adding dimethyl sulfate and DMF into a four-mouth bottle, heating to 60 ℃, and reacting for 4 hours;
s12, dripping 2M tetrahydrofuran solution of dimethylamine, slightly releasing heat at the early stage, and adding toluene after dripping;
s13, heating to 70 ℃, and carrying out reflux reaction for 1h;
cooling the reaction liquid of S14 to room temperature, standing for layering, and washing the lower layer with methyl tert-butyl ether for three times to obtain an intermediate, wherein the reaction formula is as follows;
s21, adding diethyl ether and potassium tert-butoxide into a reaction bottle, dropwise adding the intermediate at room temperature, and reacting at room temperature overnight after dropwise adding;
s22, filtering, washing a filter cake with diethyl ether, concentrating the filtrate under reduced pressure, and distilling the concentrated solution by using a water pump to obtain the product, wherein the nuclear magnetic content is about 99.4%, the total yield of the two steps is more than 85%, and the reaction formula is as follows.
Further in the present invention, the molar ratio of dimethyl sulfate to DMF is 1:1-2.
Further in the present invention, the molar ratio of dimethyl sulfate to dimethylamine is 1:1-2.
Further in the present invention, the molar ratio of dimethyl sulfate to toluene is 1:9-10.
Further in the present invention, the molar ratio of the potassium tert-butoxide to the ether is 1:5-6.
Further in the present invention, the molar ratio of the potassium tert-butoxide to the intermediate is 1:1-1.5.
The invention provides a preparation method of tert-butoxy (bisdimethylamino) methane, which has the following beneficial effects:
1. the preparation method of the tert-butoxy (bisdimethylamino) methane prepares an intermediate N, N, N ', N' -tetramethyl formamidine methyl sulfate by using tetrahydrofuran solution of N, N-dimethylformamide, dimethyl sulfate and dimethylamine as raw materials and toluene as a solvent. The tert-butoxy (bisdimethylamino) methane is prepared by reacting the ether solution of potassium tert-butoxide with the intermediate prepared in the first step, and the method has the advantages of simple process, mild reaction conditions, high safety and green chemistry accordance; the reaction sequence and the dripping sequence of the raw materials are adopted, so that the yield and the purity of the prepared tert-butoxy (bis-dimethylamino) methane are high; the scheme has stronger economical practicability and accords with industrial production.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments.
The invention provides a technical scheme that:
example 1:
the synthesis process of tert-butoxy (bisdimethylamino) methane includes the following steps:
the first step is as follows:
1. 630.0g of dimethyl sulfate and 365g of DMF are added into a four-mouth bottle, the temperature is raised to 60 ℃, and the reaction is carried out for 4 hours.
2.5L of 2M dimethylamine in tetrahydrofuran was added dropwise, with a slight exotherm in the early stage, and 5L of toluene was added after the addition.
3. Heating to 70 ℃, and refluxing for 1h.
4. The reaction solution is cooled to room temperature, and is kept stand for layering, and the lower layer is washed three times by methyl tert-butyl ether to obtain an intermediate 976.4g.
The second step is that:
1. 2.5L of diethyl ether and 5363 g of potassium tert-butoxide 538.6g are put into a reaction flask, and 3242 g of intermediate 976.4g is added dropwise at room temperature, and after the addition, the reaction is carried out overnight at room temperature.
2. Filtering, washing the filter cake with ether, concentrating the filtrate under reduced pressure, and distilling the concentrated solution with a water pump to obtain 749g of product with the nuclear magnetic content of 99.4% and the total yield of the two steps of 86%.
Example 2:
the synthesis process of tert-butoxy (bisdimethylamino) methane includes the following steps:
the first step is as follows:
1. 126.1kg of dimethyl sulfate and 73.1kg of DMF73 are pumped into the reaction kettle, the temperature is raised to 60 ℃, and the reaction lasts for 4 hours.
2. 1500L of 2M dimethylamine in tetrahydrofuran was slowly pumped in, with a slight exotherm in the early stage, and 1000L of toluene was pumped in after dripping.
3. Heating to 70 ℃, and refluxing for 1h.
4. The reaction solution is cooled to room temperature, and is kept stand for layering, and the lower layer is washed three times by methyl tert-butyl ether to obtain an intermediate 197.4kg.
The second step is that:
1. and pumping 350L of diethyl ether and 72.94kg of potassium tert-butoxide into the reaction kettle, dropwise adding 197.4kg of intermediate at room temperature, and reacting at room temperature overnight after dropwise adding.
2. Filtering, washing a filter cake with diethyl ether, concentrating the filtrate under reduced pressure, and distilling the concentrated solution by using a water pump to obtain 150.76kg of a product, wherein the nuclear magnetic content is 99.6 percent, and the total yield of the two steps is 86.5 percent.
Example 3:
the synthesis method of tert-butoxy (bisdimethylamino) methane comprises the following steps:
the first step is as follows:
1. pumping 126.1kg of dimethyl sulfate and 146.2kg of DMF146 into the reaction kettle, heating to 60 ℃, and reacting for 4 hours.
2. 1500L of 2M solution of dimethylamine in tetrahydrofuran was slowly pumped in, slightly exothermic at the front, and 1000L of toluene was pumped in after dropping.
3. Heating to 70 ℃, and refluxing for 1h.
4. The reaction solution is cooled to room temperature, and is kept stand for layering, and the lower layer is washed three times by methyl tert-butyl ether to obtain an intermediate 198.7kg.
The second step is that:
1. diethyl ether 330L and potassium tert-butoxide 71.8kg are pumped into a reaction flask, and intermediate 198.7kg is added dropwise at room temperature, and after the addition is completed, the reaction is carried out overnight at room temperature.
2. Filtering, washing the filter cake with ether, decompressing and concentrating the filtrate, distilling the concentrated solution with a water pump to obtain 151.6kg of product, 99.4 percent of nuclear magnetic content and 87 percent of total yield of the two steps.
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art should be considered to be within the technical scope of the present invention, and the technical solutions and the inventive concepts thereof according to the present invention should be equivalent or changed within the scope of the present invention.
Claims (6)
1. A preparation method of tert-butoxy (bisdimethylamino) methane is characterized by comprising the following steps: the method comprises the following steps:
s11, adding dimethyl sulfate and DMF into a four-mouth bottle, heating to 60 ℃, and reacting for 4 hours;
s12, dripping 2M tetrahydrofuran solution of dimethylamine, slightly releasing heat at the early stage, and adding toluene after dripping;
s13, heating to 70 ℃, and carrying out reflux reaction for 1h;
cooling the reaction liquid to room temperature, standing for layering, and washing the lower layer with methyl tert-butyl ether for three times to obtain an intermediate;
s21, adding diethyl ether and potassium tert-butoxide into a reaction bottle, dropwise adding the intermediate at room temperature, and reacting at room temperature overnight;
s22, filtering, washing a filter cake with diethyl ether, concentrating the filtrate under reduced pressure, and distilling the concentrated solution by using a water pump to obtain the product, wherein the nuclear magnetic content is about 99.4%, and the total yield of the two steps is over 85%.
2. The method according to claim 1, wherein the reaction mixture comprises: the molar ratio of dimethyl sulfate to DMF is 1:1-2.
3. The method for preparing tert-butoxy (bisdimethylamino) methane according to claim 1, wherein: the molar ratio of the dimethyl sulfate to the dimethylamine is 1:1-2.
4. The method according to claim 1, wherein the reaction mixture comprises: the molar ratio of dimethyl sulfate to toluene is 1:9-10.
5. The method according to claim 1, wherein the reaction mixture comprises: the molar ratio of the potassium tert-butoxide to the diethyl ether is 1:5-6.
6. The method according to claim 1, wherein the reaction mixture comprises: the molar ratio of the potassium tert-butoxide to the intermediate is 1:1-1.5.
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| CN202211693807.9A CN115772088A (en) | 2022-12-28 | 2022-12-28 | Preparation method of tert-butoxy (bisdimethylamino) methane |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101952249A (en) * | 2008-01-17 | 2011-01-19 | 诺瓦提斯公司 | Process and intermediates for the preparation of 5-biphenyl-4-yl-2-methylpentanoic acid derivatives |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101952249A (en) * | 2008-01-17 | 2011-01-19 | 诺瓦提斯公司 | Process and intermediates for the preparation of 5-biphenyl-4-yl-2-methylpentanoic acid derivatives |
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