CN103183592B - The preparation method of chloro-1,1, the 1-tri-alkoxy ethane of 2- - Google Patents
The preparation method of chloro-1,1, the 1-tri-alkoxy ethane of 2- Download PDFInfo
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- CN103183592B CN103183592B CN201110455181.3A CN201110455181A CN103183592B CN 103183592 B CN103183592 B CN 103183592B CN 201110455181 A CN201110455181 A CN 201110455181A CN 103183592 B CN103183592 B CN 103183592B
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Abstract
The invention discloses the preparation method of chloro-1,1, the 1-tri-alkoxy ethane of a kind of 2-.In existing preparation method, have not environmentally, some production costs are high, and some yields are low.The present invention is reaction media and catalyzer with polar solvent, take chlorosuccinimide as chlorinating agent, under-20 DEG C of-150 DEG C of temperature condition, reacts with ortho-acetic acid tri-alkoxy ester, chloro-1,1, the 1-tri-alkoxy ethane of preparation 2-; After completion of the reaction, crossed filter succimide by crystallization, rectification under vacuum obtains chloro-1,1, the 1-tri-alkoxy ethane of 2-after purifying.Method of the present invention is little to environmental protection pressure, substantially produces without waste; The selectivity of reaction system is up to 95%, and product content is up to 99%, and dichloro by product reduces greatly; It is the environment-friendly production process of a kind of economy, safety, applicable suitability for industrialized production.
Description
Technical field
The present invention relates to medication chemistry and pesticide chemical field, specifically the preparation method of chloro-1,1, the 1-tri-alkoxy ethane of a kind of 2-.
Background technology
Chloro-1,1, the 1-tri-alkoxy ethane of 2-is a kind of active medication chemistry and pesticide chemical intermediate of novelty, and in EP0222576A2, chloro-1,1, the 1-triethoxy ethane of 2-and 2-amino thiophenol react, and obtain 2-chloromethylbenzothiazole after process; At tetrahedron bulletin 41 (44) 8661-8664; Chloro-1,1, the 1-triethoxy ethane of 2-and semicarbazide hydrochloride Reactive Synthesis triazolone in 2000; At organic chemistry 66 (18) 6116-6123; 2001 and tetrahedron bulletin 43 (39), 7447-7452; In 2000, chloro-1,1, the 1-triethoxy ethane of 2-is used to replace ring ketal and lactone.
In US2003229255A1, adopt triethly orthoacetate and Cl
2react in alcohol solvent system, under a small amount of sodium ethylate katalysis, chloro-1,1, the 1-triethoxy ethane of preparation 2-.These processing condition adopt Cl
2as chlorinating agent, document yield only has 67%, and reaction preference is not high, by product 2, the content of chloro-1,1, the 1-triethoxy ethane of 2-bis-is up to 30%, follow-up rectification and purification must adopt relatively large reflux ratio to ensure 2 in final product, the content of chloro-1,1, the 1-triethoxy ethane of 2-bis-meets the requirement of medicine intermediate, energy consumption is large, and atom utilization is low; Cl simultaneously
2use bring the pressure of environmental protection aspect, Cl
2absorption unit too increase the input cost of equipment, technique overall operation cost is high.
Describing at EP0222576 and US4748280 adopts ortho-acetic acid tri-alkoxy (C1-C4 alkoxyl group) ester and chlorosuccinimide (NCS) to make solvent and ultraviolet lighting causes or superoxide initiation reaction at halogenated alkane, prepares 2-chloro ortho-acetic acid tri-alkoxy ester.Because NCS is almost insoluble in halogenated alkanes solvents in this system, therefore reaction is solid-liquid two phase reaction, and in order to make selectivity be improved, solvent equivalent is more than 20 times of ortho-acetic acid trialkyl ester, and solvent usage quantity is large, and solvent recuperation cost is high; Ultraviolet lighting or a small amount of superoxide initiation reaction, which increases the danger of energy consumption in production process and potential blast.
Therefore, need to develop environmental protection, the cost-effective process that one can produce chloro-1,1, the 1-tri-alkoxy ethane of 2-.
Summary of the invention
Technical problem to be solved by this invention is the defect overcoming the existence of above-mentioned prior art, 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 the safety problem that catalyst system is complicated and catalyzer is potential in subsequent processes simultaneously.
For this reason, the technical solution used in the present invention is: the preparation method of chloro-1,1, the 1-tri-alkoxy ethane of 2-, and its step is as follows:
In polar solvent, under-20 DEG C ~ 150 DEG C temperature condition, ortho-acetic acid tri-alkoxy ester (I) and chlorosuccinimide react, and prepare chloro-1,1, the 1-tri-alkoxy ethane (II) of 2-;
，
In formula (I) and (II), R
1, R
2, R
3for alkyl; After completion of the reaction, by crystallisation by cooling removing by product succimide, then rectification under vacuum purification & isolation obtains chloro-1,1, the 1-tri-alkoxy ethane of 2-.
In polar solvent, NCS and ortho-acetic acid tri-alkoxy ester react by autocatalysis, generate chloro-1,1, the 1-tri-alkoxy ethane of 2-.
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 two or more mixtures in alcohols, ester class, ketone, heterocyclic polar organic solvent, be more preferably the mixing polar organic solvent (i.e. alcohols polar solvent and another kind of polar solvent form as ester class, ketone or heterocyclic mixed solvent) containing alcohols, most preferably be the polar organic solvent of single alcohols.
As preferably, the chlorination temperature range in the present invention is 50 DEG C-80 DEG C.
Rectification under vacuum of the present invention is purified as conventional rectification under vacuum is purified.
The present invention's reaction can be carried out under normal pressure or pressure-fired condition, and selected solvent is easy in follow-up distillation or rectification and purification process and chloro-1,1, the 1-tri-alkoxy ethane separation of target product 2-preferably; Consumption is advisable with suitable value, and optimum solvent consumption is 2-10 times of ortho-acetic acid trialkyl ester volume.
After the present invention's reaction, NCS is converted into succimide, needs to carry out crystallization and de-pin material removing succimide; In reaction and rectification and purification process, have the degraded products such as ethyl acetate and occur, need to be removed 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 plays catalyzer, avoids the catalyst system using illumination or superoxide to cause; Adopt polar solvent, reaction system is homogeneous, and speed of response is faster, more controlled; Adopt the NCS of recoverable as chlorinating agent, environmental protection pressure is little, substantially produces without waste; The selectivity of reaction system is up to 95%, and product content is up to 99%, and dichloro by product reduces greatly; The present invention is the environment-friendly production process of a kind of economy, safety, applicable suitability for industrialized production.
Below in conjunction with embodiment, the invention will be further described.
Embodiment
The preparation of chloro-1,1, the 1-triethoxy ethane of embodiment 1:2-
Triethly orthoacetate 324g, NCS294g, ethanol 800ml, add in 2000ml four-hole boiling flask, back flow reaction is complete after 2 hours, and cold filtration removes insoluble succimide, after filtrate decompression separating alcohol, rectification under vacuum is purified again, divide and remove lower boiling impurity and high boiling dichloro-thing etc., obtain the 2-chloro-1,1 that content is greater than 99%, 1-triethoxy ethane product 373.5g, molar yield is 95%.
The preparation of chloro-1,1, the 1-triethoxy ethane of embodiment 2:2-
Triethly orthoacetate 324g, NCS267g, ethanol 2400ml, add in 5000ml four-hole boiling flask, 50 DEG C of reactions are complete after 10 hours, and cold filtration removes insoluble succimide, after filtrate decompression separating alcohol, rectification under vacuum is purified again, divide and remove lower boiling impurity and high boiling dichloro-thing, obtain the 2-chloro-1,1 that content is greater than 99%, 1-triethoxy ethane product 356.1g, molar yield is 90.6%.
The preparation of chloro-1,1, the 1-triethoxy ethane of embodiment 3:2-
Triethly orthoacetate 324g, NCS240g, ethanol 80ml, ethyl acetate 800ml, add in 2000ml four-hole boiling flask, back flow reaction is complete after 3 hours, cold filtration removes insoluble succimide, after filtrate decompression separating alcohol and ethyl acetate, then rectification under vacuum is purified, and point removes lower boiling impurity and high boiling dichloro-thing, obtain the 2-chloro-1 that content is greater than 99%, 1,1-triethoxy ethane product 325.2g, molar yield is 82.7%.
The preparation of chloro-1,1, the 1-triethoxy ethane of embodiment 4:2-
Triethly orthoacetate 324g, NCS294g, ethyl acetate 800ml, add in 2000ml four-hole boiling flask, back flow reaction is complete after 2 hours, and cold filtration removes insoluble succimide, after filtrate decompression separating ethyl acetate, rectification under vacuum is purified again, divide and remove lower boiling impurity and high boiling dichloro-thing etc., obtain the 2-chloro-1,1 that content is greater than 99%, 1-triethoxy ethane product 351.5g, molar yield is 89.4%.
The preparation of chloro-1,1, the 1-trimethoxy-ethane of embodiment 5:2-
Trimethyl orthoacetate 240.3g, NCS267g, methyl alcohol 1000ml, add in 2000ml four-hole boiling flask, back flow reaction is complete after 5 hours, and cold filtration removes insoluble succimide, after filtrate decompression separation of methanol, rectification under vacuum is purified again, divide and remove lower boiling impurity and high boiling dichloro-thing, obtain the 2-chloro-1,1 that content is greater than 99%, 1-trimethoxy-ethane product 283.6g, molar yield is 91.7%.
The preparation of chloro-1,1, the 1-triethoxy ethane of embodiment 6:2-
Triethly orthoacetate 324g, NCS294g, 1,4-dioxane 1000ml, adds in 2000ml four-hole boiling flask, and 75 DEG C of reactions are complete after 2.5 hours, cold filtration removes insoluble succimide, after filtrate decompression is separated Isosorbide-5-Nitrae-dioxane, rectification under vacuum is purified again, divide and remove lower boiling impurity and high boiling dichloro-thing etc., obtain the 2-chloro-1,1 that content is greater than 99%, 1-triethoxy ethane product 343.5g, molar yield is 87.4%.
The preparation of chloro-1,1, the 1-triethoxy ethane of embodiment 7:2-
Triethly orthoacetate 324g, NCS320g, acetone 1000ml, add in 2000ml four-hole boiling flask, back flow reaction is complete after 5 hours, and cold filtration removes insoluble succimide, after filtrate decompression acetone, rectification under vacuum is purified again, divide and remove lower boiling impurity and high boiling dichloro-thing etc., obtain the 2-chloro-1,1 that content is greater than 99%, 1-triethoxy ethane product 315g, molar yield is 80.2%.
The preparation of chloro-1,1, the 1-tri-butoxy ethane of embodiment 8:2-
Ortho-acetic acid tri-n-butyl 492g, NCS294g, acetone 1000ml, add in 2000ml four-hole boiling flask, back flow reaction is complete after 5 hours, and cold filtration removes insoluble succimide, after filtrate decompression acetone, rectification under vacuum is purified again, divide and remove lower boiling impurity and high boiling dichloro-thing etc., obtain the 2-chloro-1,1 that content is greater than 99%, 1-tri-butoxy ethane product 494g, molar yield is 88%.
The preparation of chloro-1,1, the 1-tripropoxy ethane of embodiment 9:2-
Ortho-acetic acid three propyl ester 408g, NCS294g, n-propyl alcohol 1000ml, add in 2000ml four-hole boiling flask, 80 DEG C of reactions are complete after 2 hours, and cold filtration removes insoluble succimide, after filtrate decompression is separated n-propyl alcohol, rectification under vacuum is purified again, divide and remove lower boiling impurity and high boiling dichloro-thing etc., obtain the 2-chloro-1,1 that content is greater than 99%, 1-tripropoxy ethane product 435g, molar yield is 91.2%.
The preparation of chloro-1,1,1-tri-ethyl isopropyl ether of embodiment 10:2-
Ortho-acetic acid three isopropyl ester 408g, NCS213g, Virahol 100ml, ethyl acetate 900ml, adds in 2000ml four-hole boiling flask, and 80 DEG C of reactions are complete after 2 hours, cold filtration removes insoluble succimide, after filtrate decompression separating isopropanol and ethyl acetate, then rectification under vacuum is purified, and point removes lower boiling impurity and high boiling dichloro-thing etc., obtain the 2-chloro-1 that content is greater than 99%, 1,1-tri-ethyl isopropyl ether product 352g, molar yield is 73.8%.
Claims (8)
- The preparation method of chloro-1,1, the 1-tri-alkoxy ethane of 1.2-, its step is as follows:In polar solvent, under-20 DEG C ~ 150 DEG C temperature condition, ortho-acetic acid tri-alkoxy ester (I) and chlorosuccinimide react, and prepare chloro-1,1, the 1-tri-alkoxy ethane (II) of 2-;, in formula (I) and (II), R 1, R 2, R 3for alkyl; After completion of the reaction, by crystallisation by cooling removing by product succimide, then rectification under vacuum purification & isolation obtains chloro-1,1, the 1-tri-alkoxy ethane of 2-;Described polar solvent is any one or two or more mixtures in alcohols, ester class, ketone polar organic solvent.
- 2. the preparation method of chloro-1,1, the 1-tri-alkoxy ethane of 2-according to claim 1, is characterized in that, described R 1, R 2, R 3for the straight or branched alkyl of 1-4 carbon atom.
- 3. the preparation method of chloro-1,1, the 1-tri-alkoxy ethane of 2-according to claim 1, is characterized in that, described polar solvent is by distillation or rectifying is easy and the polar organic solvent of chloro-1,1, the 1-tri-alkoxy ethane separation of target product 2-.
- 4. the preparation method of chloro-1,1, the 1-tri-alkoxy ethane of 2-according to claim 3, is characterized in that, described polar solvent is the mixed solvent that alcohols polar solvent and another kind of polar solvent form.
- 5. the preparation method of chloro-1,1, the 1-tri-alkoxy ethane of 2-according to claim 3, it is characterized in that, described polar solvent is alcohols polar solvent.
- 6. the preparation method of chloro-1,1, the 1-tri-alkoxy ethane of 2-according to claim 5, is characterized in that, the consumption of polar solvent is 2-10 times of ortho-acetic acid trialkyl ester volume.
- 7. the preparation method of chloro-1,1, the 1-tri-alkoxy ethane of 2-according to claim 1, it is characterized in that, described temperature of reaction is 50 DEG C-80 DEG C.
- 8. the preparation method of chloro-1,1, the 1-tri-alkoxy ethane of 2-according to claim 1, is characterized in that, chlorosuccinimide is 0.8-1.2:1 with the molar equivalent ratio of ortho-acetic acid trialkyl ester.
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| 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 |
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) |
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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 |
|---|
| New Methodologies for the Synthesis of 3-Acylpyridone Metabolites;Raymond C.F.Jones et al;《Synlett》;20100119(第4期);654-658 * |
| 吉莫斯特的合成;郝玲花等;《沈阳药科大学学报》;20051130;第22卷(第6期);420-421、433 * |
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