CN102952017A - Preparation method of 2-acetylchloromethoxy-1,3-dichloropropane - Google Patents
Preparation method of 2-acetylchloromethoxy-1,3-dichloropropane Download PDFInfo
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- CN102952017A CN102952017A CN2011102536541A CN201110253654A CN102952017A CN 102952017 A CN102952017 A CN 102952017A CN 2011102536541 A CN2011102536541 A CN 2011102536541A CN 201110253654 A CN201110253654 A CN 201110253654A CN 102952017 A CN102952017 A CN 102952017A
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- ylmethoxy
- acetyl chloride
- chloride 98min
- propylene dichloride
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Abstract
The invention relates to a preparation method of 2-acetylchloromethoxy-1,3-dichloropropane, which comprises the following steps: extracting the following substances: 250kg of 1,3-dichloro-2-propanol, 60kg of polyformaldehyde, 3.68kg of sulfuric acid, 250kg of acetic anhydride and 5kg of postassium acetate; adding the 1,3-dichloro-2-propanol, polyformaldehyde and sulfuric acid into a clean and dry reaction kettle, slowly heating to 96-98 DEG C within 2 hours, and keeping the temperature for 2 hours; after finishing keeping the temperature, cooling to 10 DEG C, and dropwisely adding the acetic anhydride while keeping the temperature at 15-20 DEG C; and after finishing the dropwise addition, heating to 35-40 DEG C, keeping the temperature for 10 hours, adding postassium acetate, stirring, recovering the acetic anhydride in vacuum to 100 DEG C, cooling to 20 DEG C, filtering, sucking the filtrate into a rectifying still, and collecting the fraction in the 115 DEG C/10mmHg state, thereby obtaining the 2-acetylchloromethoxy-1,3-dichloropropane of which the weight yield is 80% and the content is greater than or equal to 95%. The invention lowers the production cost and enhances the yield.
Description
Technical field
The invention belongs to chemical industry field or pharmacy field, specifically refer to the preparation method of a kind of 2-Acetyl Chloride 98Min. ylmethoxy-1.3-propylene dichloride.
Background technology
2-Acetyl Chloride 98Min. ylmethoxy-1.3-propylene dichloride (hereinafter to be referred as the chlorine methoxyethoxy ester) is the main intermediate of antivirus raw material medicine ganciclovir, at home, all there is larger market the world.This product is continued to use initial process always from domestic putting goods on the market in 1998, be characterized in: 1, the production time long, about five days (120h); 2, production stage had 5 steps; 3, use a kind solvent purified petroleum benzin; 4, recovery rate only has about 55%.
Its chemical equation is:
The first step:
Second step:
Operation: in the 1000L of clean dried reactor, add 1.3-two chloro-2 propyl alcohol and the stirring that configure, add Paraformaldehyde 96, finish, slowly add the vitriol oil, lock clean-out cover, slowly heat up, in about 2 hours, be warmed up to 96-98 ℃, and be incubated 2 hours.Insulation is finished, and cools to below 40 ℃, adds pure stupidly, is warming up to backflow, and reflux dewatering is to the greatest extent.Need 16 hours approximately, cool to below 30 ℃, add Potassium ethanoate 5kg, left standstill after the stirring 2 hours.
Extract supernatant liquor in still kettle, first normal pressure reclaims purified petroleum benzin to 100 ℃, cools to 60 ℃, and unreacted 1.3-two chloro-of vacuum distilling 2 propyl alcohol cool to 60 ℃ to 140 ℃ of interior temperature, add ethanol 100kg, cool to 0 ℃ and get rid of material, get the acetal crude product.
Crude product adds 400kg ethanol rising temperature for dissolving, adds gac 5kg decolouring 30 minutes, filters, and filtrate is cooled to 0 ℃ and gets the acetal elaboration, and elaboration is in 40-50 ℃ of oven dry, weight yield 70%.
Get acetal 250kg aceticanhydride 375kg sulfuric acid 1.84kg Potassium ethanoate 2kg
In the reactor of clean dried, drop into aceticanhydride, acetal, slowly add sulfuric acid, in 80 ℃ of insulations 10 hours, cool to 30 ℃, add Potassium ethanoate and stirred 15 minutes, steam diluted acid and be cooled to 10 ℃ of filtrations, in the filtrate suction rectifying still, collect 115 ℃/10mmHg and heat up in a steamer confusingly weight yield 75%, content 〉=90%.These all forms have certain limitation: or easily variable color or use inconvenience, mouthfeel is not good enough, or with high costs; Thereby be necessary to be innovated on this basis and explore new production technique.
Summary of the invention
The preparation method who the purpose of this invention is to provide a kind of 2-Acetyl Chloride 98Min. ylmethoxy-1.3-propylene dichloride.
Technical solution of the present invention is as follows:
The preparation method of a kind of 2-Acetyl Chloride 98Min. ylmethoxy-1.3-propylene dichloride is provided, and its chemical equation is as follows:
Only need sequentially choose reactant and resultant and one step of catalyzer and finish following reaction:
It is characterized in that:
By weight extracting following material:
In the clean dried reactor, add 1.3-two chloro-2-propyl alcohol, Paraformaldehyde 96, sulfuric acid, slowly heat up, be warming up to 96-98 ℃ in 2 hours, be incubated 2 hours, insulation is finished, cool to 10 ℃ and begin to drip aceticanhydride, temperature remains on 15-20 ℃, finishes, heat up in 35-40 ℃ of insulation 10 hours, add Potassium ethanoate, stir, vacuum reclaims aceticanhydride to 100 ℃, be cooled to 20 ℃, filter, in the filtrate suction rectifying still, collect heating up in a steamer confusingly of steaming under the 115 ℃/10mmHg state, namely get weight yield 80%, the 2-Acetyl Chloride 98Min. ylmethoxy of content 〉=95%-1.3-propylene dichloride.
The preparation method of aforesaid 2-Acetyl Chloride 98Min. ylmethoxy-1.3-propylene dichloride, it is characterized in that: before the described dropping aceticanhydride, heating up in a steamer of steaming under 115 ℃/10mmHg state when adding 250kg rectifying is confused, the yield 90% of 2-Acetyl Chloride 98Min. ylmethoxy-1.3-propylene dichloride; This preparation method is applicable to since the second material.
Target:
1, do not use a kind solvent pure stupid.
2, reduce the aceticanhydride consumption, do not use ethanol, slightly increase the Paraformaldehyde 96 consumption.
3, time shorten to 50 hour.
4, cost only be equivalent to original half, quality has significantly and to improve, and can reach 99% (because the reaction times is short, side reaction is few, and impurity phase is conducive to fractionation to few).
Embodiment
The below provides embodiments of the invention, but is not limited to present embodiment:
Embodiment 1:
By weight extracting following material:
In the clean dried reactor, add 1.3-two chloro-2-propyl alcohol, Paraformaldehyde 96, sulfuric acid, slowly heat up, be warming up to 96-98 ℃ in 2 hours, be incubated 2 hours, insulation is finished, cool to 10 ℃ and begin to drip aceticanhydride, temperature remains on 15-20 ℃, finishes, heat up in 35-40 ℃ of insulation 10 hours, add Potassium ethanoate, stir, vacuum reclaims aceticanhydride to 100 ℃, be cooled to 20 ℃, filter, in the filtrate suction rectifying still, collect 115 ℃/10mmHg and heat up in a steamer confusingly, namely get weight yield 80%, the 2-Acetyl Chloride 98Min. ylmethoxy of content 〉=95%-1.3-propylene dichloride.
Embodiment 2:
Since the second material, by weight extracting following material:
In the clean dried reactor, add 1.3-two chloro-2-propyl alcohol, Paraformaldehyde 96, sulfuric acid slowly heats up, be warming up to 96-98 ℃ in 2 hours, be incubated 2 hours, insulation is finished, and cools to 10 ℃, when adding rectifying described in the 250kg embodiment 1 115 ℃/steam below the 10mmHg heat up in a steamer confused, begin to drip aceticanhydride, temperature remains on 15-20 ℃, finishes again, heat up in 35-40 ℃ of insulation 10 hours, add Potassium ethanoate, stir, vacuum reclaims aceticanhydride to 100 ℃, be cooled to 20 ℃, filter, in the filtrate suction rectifying still, collect 115 ℃/10mmHg and heat up in a steamer confusingly, namely get weight yield 90%, the 2-Acetyl Chloride 98Min. ylmethoxy of content 〉=95%-1.3-propylene dichloride.
Although above shown detailed embodiment of the present invention, those skilled in the art is under prerequisite of the present invention, can carry out the part modifications and changes; The content of mentioning in the description above is the illustration of property as an illustration only, is not limitation of the present invention, has the preparation method of the 2-Acetyl Chloride 98Min. ylmethoxy of technical characterictic of the present invention-1.3-propylene dichloride, all falls into scope of patent protection shown in the present.
Claims (2)
1. the preparation method of 2-Acetyl Chloride 98Min. ylmethoxy-1.3-propylene dichloride is characterized in that: by weight extracting following material:
In the clean dried reactor, add 1.3-two chloro-2-propyl alcohol, Paraformaldehyde 96, sulfuric acid, slowly heat up, be warming up to 96-98 ℃ in 2 hours, be incubated 2 hours, insulation is finished, cool to 10 ℃ and begin to drip aceticanhydride, temperature remains on 15-20 ℃, finishes, heat up in 35-40 ℃ of insulation 10 hours, add Potassium ethanoate, stir, vacuum reclaims aceticanhydride to 100 ℃, be cooled to 20 ℃, filter, in the filtrate suction rectifying still, collect heating up in a steamer confusingly of steaming under the 115 ℃/10mmHg state, namely get weight yield 80%, the 2-Acetyl Chloride 98Min. ylmethoxy of content 〉=95%-1.3-propylene dichloride.
2. the preparation method of 2-Acetyl Chloride 98Min. ylmethoxy as claimed in claim 1-1.3-propylene dichloride, it is characterized in that: before the described dropping aceticanhydride, heating up in a steamer of steaming under 115 ℃/10mmHg state when adding 250kg rectifying is confused, the yield 90% of 2-Acetyl Chloride 98Min. ylmethoxy-1.3-propylene dichloride.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN2011102536541A CN102952017A (en) | 2011-08-24 | 2011-08-24 | Preparation method of 2-acetylchloromethoxy-1,3-dichloropropane |
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| CN2011102536541A CN102952017A (en) | 2011-08-24 | 2011-08-24 | Preparation method of 2-acetylchloromethoxy-1,3-dichloropropane |
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| CN2011102536541A Pending CN102952017A (en) | 2011-08-24 | 2011-08-24 | Preparation method of 2-acetylchloromethoxy-1,3-dichloropropane |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105837440A (en) * | 2016-04-13 | 2016-08-10 | 安徽海康药业有限责任公司 | Preparation technology of 1,3-dichloro-2-acetyl methoxy propane |
Citations (5)
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|---|---|---|---|---|
| US2314454A (en) * | 1938-08-19 | 1943-03-23 | Gen Aniline & Film Corp | Production of esters of halogen alcohols |
| CN86100170A (en) * | 1985-01-14 | 1986-12-17 | 辛恩-泰克有限公司 | The preparation method of propanol derivative |
| US5654472A (en) * | 1994-04-19 | 1997-08-05 | Kanegafuchi Kagaku Kogyo Kabushiki Kaisha | Triazole derivatives |
| CN1301702A (en) * | 1999-12-29 | 2001-07-04 | 湖北省医药工业研究院 | Internmediate of anti viral medicine, their preparation and use |
| CN101475572A (en) * | 2009-01-15 | 2009-07-08 | 张小顺 | Chemical synthesis of triacetylganciclovir |
-
2011
- 2011-08-24 CN CN2011102536541A patent/CN102952017A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2314454A (en) * | 1938-08-19 | 1943-03-23 | Gen Aniline & Film Corp | Production of esters of halogen alcohols |
| CN86100170A (en) * | 1985-01-14 | 1986-12-17 | 辛恩-泰克有限公司 | The preparation method of propanol derivative |
| US5654472A (en) * | 1994-04-19 | 1997-08-05 | Kanegafuchi Kagaku Kogyo Kabushiki Kaisha | Triazole derivatives |
| CN1301702A (en) * | 1999-12-29 | 2001-07-04 | 湖北省医药工业研究院 | Internmediate of anti viral medicine, their preparation and use |
| CN101475572A (en) * | 2009-01-15 | 2009-07-08 | 张小顺 | Chemical synthesis of triacetylganciclovir |
Non-Patent Citations (1)
| Title |
|---|
| 陈文华: "1,3-二乙酰氧基-2-乙酰氧基甲氧基丙烷的合成", 《化学试剂》, vol. 29, no. 02, 15 February 2007 (2007-02-15), pages 119 - 120 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105837440A (en) * | 2016-04-13 | 2016-08-10 | 安徽海康药业有限责任公司 | Preparation technology of 1,3-dichloro-2-acetyl methoxy propane |
| CN105837440B (en) * | 2016-04-13 | 2018-12-11 | 安徽海康药业有限责任公司 | A kind of preparation process of the chloro- 2- acetyl group methoxy propane of 1,3- bis- |
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