CN103183592A - Preparation method of 2-chloro-1,1,1-trialkoxy ethane - Google Patents
Preparation method of 2-chloro-1,1,1-trialkoxy ethane Download PDFInfo
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- CN103183592A CN103183592A CN2011104551813A CN201110455181A CN103183592A CN 103183592 A CN103183592 A CN 103183592A CN 2011104551813 A CN2011104551813 A CN 2011104551813A CN 201110455181 A CN201110455181 A CN 201110455181A CN 103183592 A CN103183592 A CN 103183592A
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Abstract
The invention discloses a preparation method of 2-chloro-1,1,1-trialkoxy ethane. The current preparation methods have the disadvantages of environmental unfriendliness, high production cost and low yield. According to the invention, a polar solvent is taken as a reaction medium and a catalyst, chlorosuccinimide is taken as a chlorinated reagent, and is reacted with trialkoxy orthoacetate to prepare 2-chloro-1,1,1-trialkoxy ethane at the temperature of -20 DEG C-150 DEG C; after finishing the reaction, succimide is removed through crystallization and filtering, and then 2-chloro-1,1,1-trialkoxy ethane can be obtained through vacuum rectification and purification. The method provided by the invention has small pressure on environmental protection, no waste is generated; the selectivity of a reaction system reaches as high as 95%, the content of the product can reach as high as 99%, the dichloro by-product is greatly reduced, and the method is an environment-friendly type production technology suitable for industrial production with characteristics of economy and safety.
Description
Technical field
The present invention relates to medication chemistry and pesticide chemical field, a kind of 2-chloro-1,1 specifically, the preparation method of 1-tri-alkoxy ethane.
Background technology
2-chloro-1,1,1-tri-alkoxy ethane are a kind of active medication chemistry and pesticide chemical intermediates of novelty, 2-chloro-1,1 among the EP0222576A2, and the amino thiophenol of 1-triethoxy ethane and 2-reacts, and obtains 2-chloromethyl benzo thiazole after the processing; At tetrahedron wall bulletin 41 (44) 8661-8664; 2-chloro-1,1 in 2000,1-triethoxy ethane and the synthetic triazolone of semicarbazide hydrochloride reaction; At organic chemistry 66 (18) 6116-6123; 2001 and tetrahedron wall bulletin 43 (39), 7447-7452; In 2000,2-chloro-1,1,1-triethoxy ethane are used to replace ring ketal and lactone.
Among the US2003229255A1, adopt triethly orthoacetate and Cl
2In the alcohol solvent system, react, under a spot of sodium ethylate katalysis, preparation 2-chloro-1,1,1-triethoxy ethane.These processing condition adopt Cl
2As chlorinating agent, the document yield has only 67%, and reaction preference is not high, by product 2,2-two chloro-1,1, the content of 1-triethoxy ethane is up to 30%, follow-up rectification and purification must adopt relatively large reflux ratio to guarantee 2 in the final product, 2-two chloro-1,1, the content of 1-triethoxy ethane meets the requirement of medicine intermediate, energy consumption is big, and atom utilization is low; While Cl
2Use brought the pressure of environmental protection aspect, Cl
2Absorption unit also increased the input cost of equipment, technology overall operation cost height.
Adopt ortho-acetic acid tri-alkoxy (C1-C4 alkoxyl group) ester and chlorosuccinimide (NCS) to do solvent and ultraviolet lighting initiation or superoxide initiation reaction at halogenated alkane at EP0222576 and US4748280 description, preparation 2-chloro ortho-acetic acid tri-alkoxy ester.Because NCS is almost insoluble in the halogenated alkane kind solvent, so reaction is improved in order to make selectivity for the solid-liquid two phase reaction, the solvent equivalent is more than 20 times of ortho-acetic acid trialkyl ester in this system, and the solvent usage quantity is big, solvent recuperation cost height; Ultraviolet lighting or a spot of superoxide initiation reaction, this has also increased energy consumption in the production process and the danger of potential blast.
Therefore, the needs exploitation is a kind of can produce 2-chloro-1,1, the environmental protection of 1-tri-alkoxy ethane, economical technology.
Summary of the invention
Technical problem to be solved by this invention is to overcome the defective that above-mentioned prior art exists, a kind of 2-chloro-1 is provided, 1, the preparation method of 1-tri-alkoxy ethane, it can avoid using halogenated alkane to make solvent, can solve simultaneously catalyst system complexity and catalyzer potential safety problem in subsequent processes.
For this reason, the technical solution used in the present invention is: 2-chloro-1,1, and the preparation method of 1-tri-alkoxy ethane, its step is as follows:
In polar solvent, under-20 ℃～150 ℃ temperature condition, ortho-acetic acid tri-alkoxy ester (I) reacts with chlorosuccinimide, prepares 2-chloro-1,1,1-tri-alkoxy ethane (II);
, formula (I) and (II) in, R
1, R
2, R
3Be alkyl; After reaction finishes, remove the by product succimide by crystallisation by cooling, rectification under vacuum is purified to separate and is obtained 2-chloro-1,1,1-tri-alkoxy ethane then.
In polar solvent, NCS and ortho-acetic acid tri-alkoxy ester can react by autocatalysis, generate 2-chloro-1,1,1-tri-alkoxy ethane.
As preferably, described R
1, R
2, R
3For the straight or branched alkyl of 1-4 carbon atom, as methyl, ethyl, propyl group, sec.-propyl, normal-butyl, isobutyl-etc.
Described polar solvent is preferably any one or the two or more mixtures in alcohols, ester class, ketone, the heterocyclic polar organic solvent, the mixing polar organic solvent (being the mixed solvent that alcohols polar solvent and another kind of polar solvent such as ester class, ketone or heterocyclic are formed) that more preferably contains alcohols most preferably is the polar organic solvent of single alcohols.
As preferably, the chlorination temperature range among the present invention is 50 ℃-80 ℃.
Rectification under vacuum of the present invention is purified and is conventional rectification under vacuum purification.
The present invention's reaction can be carried out under normal pressure or pressure-fired condition, and selected solvent is preferably in easy and target product 2-chloro-1,1 in follow-up distillation or the rectification and purification process, 1-tri-alkoxy ethane separation; Consumption is advisable with suitable value, and the optimum solvent consumption is 2-10 times of ortho-acetic acid trialkyl ester volume.
After the present invention reaction, NCS is converted into succimide, need carry out crystallization and takes off the pin material and remove succimide; In reaction and rectification and purification process, have degraded product appearance such as ethyl acetate, need remove by rectification and purification.
Compared with prior art, the polar solvent that the present invention adopts not only plays the effect of reaction solvent in reaction system, also play catalyzer, has avoided the catalyst system that uses illumination or superoxide to cause; Adopt polar solvent, the reaction system homogeneous, speed of response is faster, and is more controlled; Adopt the NCS of recyclable utilization as chlorinating agent, environmental protection pressure is little, does not have generation of waste materials substantially; The selectivity of reaction system is up to 95%, and product content is up to 99%, and the dichloro by product reduces greatly; The present invention is the environment-friendly production process of a kind of economy, safety, suitable suitability for industrialized production.
The invention will be further described below in conjunction with embodiment.
Embodiment
Embodiment 1:2-chloro-1,1, the preparation of 1-triethoxy ethane
Triethly orthoacetate 324g, NCS294g, ethanol 800ml, add in the 2000ml four-hole boiling flask, back flow reaction finished after 2 hours, and cold filtration is removed insoluble succimide, behind the filtrate decompression separating alcohol, rectification under vacuum is purified again, divide and to remove lower boiling impurity and high boiling dichloro-thing etc., get content greater than 99% 2-chloro-1,1,1-triethoxy ethane product 373.5g, molar yield is 95%.
Embodiment 2:2-chloro-1,1, the preparation of 1-triethoxy ethane
Triethly orthoacetate 324g, NCS267g, ethanol 2400ml, add in the 5000ml four-hole boiling flask, 50 ℃ of reactions finished after 10 hours, and cold filtration is removed insoluble succimide, behind the filtrate decompression separating alcohol, rectification under vacuum is purified again, divide and to remove lower boiling impurity and high boiling dichloro-thing, get content greater than 99% 2-chloro-1,1,1-triethoxy ethane product 356.1g, molar yield is 90.6%.
Embodiment 3:2-chloro-1,1, the preparation of 1-triethoxy ethane
Triethly orthoacetate 324g, NCS240g, ethanol 80ml, ethyl acetate 800ml adds in the 2000ml four-hole boiling flask, and back flow reaction finished after 3 hours, cold filtration is removed insoluble succimide, after filtrate decompression separating alcohol and the ethyl acetate, rectification under vacuum is purified again, divides and removes lower boiling impurity and high boiling dichloro-thing, content greater than 99% 2-chloro-1,1,1-triethoxy ethane product 325.2g, molar yield is 82.7%.
Embodiment 4:2-chloro-1,1, the preparation of 1-triethoxy ethane
Triethly orthoacetate 324g, NCS294g, ethyl acetate 800ml, add in the 2000ml four-hole boiling flask, back flow reaction finished after 2 hours, and cold filtration is removed insoluble succimide, behind the filtrate decompression separating ethyl acetate, rectification under vacuum is purified again, divide and to remove lower boiling impurity and high boiling dichloro-thing etc., get content greater than 99% 2-chloro-1,1,1-triethoxy ethane product 351.5g, molar yield is 89.4%.
Embodiment 5:2-chloro-1,1, the preparation of 1-trimethoxy-ethane
Trimethyl orthoacetate 240.3g, NCS267g, methyl alcohol 1000ml, add in the 2000ml four-hole boiling flask, back flow reaction finished after 5 hours, and cold filtration is removed insoluble succimide, behind the filtrate decompression separation of methanol, rectification under vacuum is purified again, divide and to remove lower boiling impurity and high boiling dichloro-thing, get content greater than 99% 2-chloro-1,1,1-trimethoxy-ethane product 283.6g, molar yield is 91.7%.
Embodiment 6:2-chloro-1,1, the preparation of 1-triethoxy ethane
Triethly orthoacetate 324g, NCS294g, 1,4-dioxane 1000ml adds in the 2000ml four-hole boiling flask, and 75 ℃ of reactions finished after 2.5 hours, cold filtration is removed insoluble succimide, after filtrate decompression is separated 1,4-dioxane, rectification under vacuum is purified again, divide and to remove lower boiling impurity and high boiling dichloro-thing etc., get content greater than 99% 2-chloro-1,1,1-triethoxy ethane product 343.5g, molar yield is 87.4%.
Embodiment 7:2-chloro-1,1, the preparation of 1-triethoxy ethane
Triethly orthoacetate 324g, NCS320g, acetone 1000ml, add in the 2000ml four-hole boiling flask, back flow reaction finished after 5 hours, and cold filtration is removed insoluble succimide, behind the filtrate decompression acetone, rectification under vacuum is purified again, divide and to remove lower boiling impurity and high boiling dichloro-thing etc., get content greater than 99% 2-chloro-1,1,1-triethoxy ethane product 315g, molar yield is 80.2%.
Embodiment 8:2-chloro-1,1, the preparation of 1-three butoxy ethane
Ortho-acetic acid tri-n-butyl 492g, NCS294g, acetone 1000ml, add in the 2000ml four-hole boiling flask, back flow reaction finished after 5 hours, and cold filtration is removed insoluble succimide, behind the filtrate decompression acetone, rectification under vacuum is purified again, divide and to remove lower boiling impurity and high boiling dichloro-thing etc., get content greater than 99% 2-chloro-1,1,1-three butoxy ethane product 494g, molar yield is 88%.
Embodiment 9:2-chloro-1,1, the preparation of 1-tripropoxy ethane
Ortho-acetic acid three propyl ester 408g, NCS294g, n-propyl alcohol 1000ml, add in the 2000ml four-hole boiling flask, 80 ℃ of reactions finished after 2 hours, and cold filtration is removed insoluble succimide, after filtrate decompression is separated n-propyl alcohol, rectification under vacuum is purified again, divide and to remove lower boiling impurity and high boiling dichloro-thing etc., get content greater than 99% 2-chloro-1,1,1-tripropoxy ethane product 435g, molar yield is 91.2%.
Embodiment 10:2-chloro-1,1, the preparation of 1-three ethyl isopropyl ethers
Ortho-acetic acid three isopropyl ester 408g, NCS213g, Virahol 100ml, ethyl acetate 900ml adds in the 2000ml four-hole boiling flask, and 80 ℃ of reactions finished after 2 hours, cold filtration is removed insoluble succimide, after filtrate decompression separating isopropanol and the ethyl acetate, rectification under vacuum is purified again, divides and removes lower boiling impurity and high boiling dichloro-thing etc., content greater than 99% 2-chloro-1,1,1-, three ethyl isopropyl ether product 352g, molar yield is 73.8%.
Claims (9)
1.2-chloro-1,1, the preparation method of 1-tri-alkoxy ethane, its step is as follows:
In polar solvent, under-20 ℃～150 ℃ temperature condition, ortho-acetic acid tri-alkoxy ester (I) reacts with chlorosuccinimide, prepares 2-chloro-1,1,1-tri-alkoxy ethane (II);
, formula (I) and (II) in, R
1, R
2, R
3Be alkyl; After reaction finishes, remove the by product succimide by crystallisation by cooling, rectification under vacuum is purified to separate and is obtained 2-chloro-1,1,1-tri-alkoxy ethane then.
2. 2-chloro-1,1 according to claim 1, the preparation method of 1-tri-alkoxy ethane is characterized in that, described R
1, R
2, R
3Straight or branched alkyl for 1-4 carbon atom.
3. 2-chloro-1,1 according to claim 1, the preparation method of 1-tri-alkoxy ethane is characterized in that, described polar solvent is any one or the two or more mixture in alcohols, ester class, ketone, the heterocyclic polar organic solvent.
4. 2-chloro-1,1 according to claim 3, the preparation method of 1-tri-alkoxy ethane is characterized in that, described polar solvent is for by distillation or rectifying easily and target product 2-chloro-1,1, the polar organic solvent of 1-tri-alkoxy ethane separation.
5. 2-chloro-1,1 according to claim 4, the preparation method of 1-tri-alkoxy ethane is characterized in that, described polar solvent is the mixed solvent that alcohols polar solvent and another kind of polar solvent are formed.
6. 2-chloro-1,1 according to claim 4, the preparation method of 1-tri-alkoxy ethane is characterized in that, described polar solvent is the alcohols polar solvent.
7. 2-chloro-1,1 according to claim 6, the preparation method of 1-tri-alkoxy ethane is characterized in that, the consumption of polar solvent be ortho-acetic acid trialkyl ester volume 2-10 doubly.
8. 2-chloro-1,1 according to claim 1, the preparation method of 1-tri-alkoxy ethane is characterized in that, described temperature of reaction is 50 ℃-80 ℃.
9. 2-chloro-1,1 according to claim 1, the preparation method of 1-tri-alkoxy ethane is characterized in that, the molar equivalent of chlorosuccinimide and ortho-acetic acid trialkyl ester is than being 0.8-1.2: 1.
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| CN201110455181.3A CN103183592B (en) | 2011-12-30 | 2011-12-30 | The preparation method of chloro-1,1, the 1-tri-alkoxy ethane of 2- |
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| CN201110455181.3A CN103183592B (en) | 2011-12-30 | 2011-12-30 | The preparation method of chloro-1,1, the 1-tri-alkoxy ethane of 2- |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105367391A (en) * | 2015-12-15 | 2016-03-02 | 新乡科信化工有限公司 | 2-chlorine-1,1,1-trimethoxyethane preparing method |
| CN112745282A (en) * | 2019-10-31 | 2021-05-04 | 常州强力电子新材料股份有限公司 | Preparation method of 3-chloromethyl-3-ethyl oxetane |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4748280A (en) * | 1985-11-07 | 1988-05-31 | Pfizer Inc. | Certain chlorination process for preparing 2-chloro-1,1,1-(C1 -C6) |
-
2011
- 2011-12-30 CN CN201110455181.3A patent/CN103183592B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4748280A (en) * | 1985-11-07 | 1988-05-31 | Pfizer Inc. | Certain chlorination process for preparing 2-chloro-1,1,1-(C1 -C6) |
Non-Patent Citations (2)
| Title |
|---|
| RAYMOND C.F.JONES ET AL: "New Methodologies for the Synthesis of 3-Acylpyridone Metabolites", 《SYNLETT》 * |
| 郝玲花等: "吉莫斯特的合成", 《沈阳药科大学学报》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105367391A (en) * | 2015-12-15 | 2016-03-02 | 新乡科信化工有限公司 | 2-chlorine-1,1,1-trimethoxyethane preparing method |
| CN112745282A (en) * | 2019-10-31 | 2021-05-04 | 常州强力电子新材料股份有限公司 | Preparation method of 3-chloromethyl-3-ethyl oxetane |
| CN112745282B (en) * | 2019-10-31 | 2022-04-22 | 常州强力电子新材料股份有限公司 | Preparation method of 3-chloromethyl-3-ethyl oxetane |
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