CN102757311A - Preparation method of 1, 1-cyclopropane dimethanol - Google Patents
Preparation method of 1, 1-cyclopropane dimethanol Download PDFInfo
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- CN102757311A CN102757311A CN2012102168633A CN201210216863A CN102757311A CN 102757311 A CN102757311 A CN 102757311A CN 2012102168633 A CN2012102168633 A CN 2012102168633A CN 201210216863 A CN201210216863 A CN 201210216863A CN 102757311 A CN102757311 A CN 102757311A
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Abstract
The invention relates to a preparation method of 1, 1-cyclopropane dimethanol. The method comprises the steps of conducting ring-closure reaction on organic dihalide and a reducing agent in an alcohol solvent under a certain condition to obtain a solution of 1, 1-cyclopropane dimethanol and halide salt, introducing ammonia under certain conditions so as to conduct solid-liquid separation, filter and rectify to obtain 1, 1-cyclopropane dimethanol. Due to the adoption of the preparation method, the process of 1, 1-cyclopropane dimethanol is simple and concise, the safety is high, and meanwhile, the yield reaches to more than 90%, the purity of 1, 1-cyclopropane dimethanol is more than 98%, and the quality of 1, 1-cyclopropane dimethanol is improved effectively.
Description
Technical field
The present invention relates to a kind ofly 1,1-encircles the preparation method of third dimethanol.
Background technology
1,1-encircles third dimethanol as Menglusitena (Montelukast) side chain synthetic important intermediate, and its compound method receives much concern.More traditional method is a raw material with the ethyl malonate exactly, obtains 1 through C-hydrocarbonylation, two steps of reduction, and 1-encircles third dimethanol; Wherein in the C-alkylation reaction; With polyoxyethylene glycol (PEG) 400 as phase-transfer catalyst catalysis, and under the salt of wormwood effect, with l; The reaction of 2 one ethylene dichloride obtains l, 1 one vinaconic acid diethyl esters; In reduction reaction, use potassium borohydride reduction, with 1, the reduction of 1-vinaconic acid diethyl ester obtains 1 under aluminum chloride catalysis, and 1-encircles third dimethanol, two step overall yield of reaction 50%～55%.This method steps is loaded down with trivial details, or uses the bigger solvent of toxicity, or uses the somewhat expensive again reductive agent of poor stability, in art production process, has many problems, can't satisfy the demand of the pharmaceutical prod of high speed development to midbody.
Summary of the invention
What the purpose of this invention is to provide that technology is succinct, safe, yield is high, quality product is high is a kind of 1, and 1-encircles the preparation method of third dimethanol.
The technical scheme that the present invention takes is: a kind of 1,1-encircles the preparation method of third dimethanol, it is characterized in that organic dihalide is carried out ring-closure reaction under certain condition with reductive agent in alcoholic solvent; Obtain 1,1-encircles the solution of third dimethanol and halide salt, and logical under certain condition again ammonia carries out solid-liquid separation; Filter; Rectifying obtains 1, and 1-encircles third dimethanol.
Described organic dihalide is dichloro NSC 6366, dibromoneopentyl glycol.
Described alcoholic solvent is methyl alcohol, ethanol, Virahol, propyl carbinol, preferential ethanol.
Described reductive agent is iron powder, zinc powder, nickel powder, preferential zinc powder.
The mol ratio of said dibromoneopentyl glycol and zinc powder and solvent is: 1:1～1.5:10～50, preferential 1:1.2:40.
Said zinc powder is 200 orders, 320 orders, 400 orders, preferential 320 orders.
Saidly carry out ring-closure reaction under certain condition, promptly reduction temperature is 25～100 degree, preferential 65 degree; Reaction times is 2～8 hours, preferred 6 hours.
Said logical under certain condition ammonia carries out solid-liquid separation, and promptly logical ammonia temperature is 0～50 degree, preferential 20 degree; The logical ammonia time is 1～6 hour, preferential 3 hours.
Adopt the present invention, preparation 1, the technology that 1-encircles third dimethanol is succinct, and is safe, and yield can reach more than 90% simultaneously, and product purity is improved the quality of products more than 98% effectively.
Embodiment
Do further explain in the face of the present invention down.
Embodiment one
In 1000 milliliters of four-hole boiling flasks that have mechanical stirring, TM, prolong, add ethanol 500g (11.1mol), and dibromoneopentyl glycol 250g (in Yixing just, 99%, 0.954mol), stir, be warming up to 60 degree; 12 addings of branch, 320 order zinc powder 70g (Taizhou zinc section, 99%, 1.07mol), added exothermic heat of reaction in the process in about 2 hours; Need logical water coolant, keep reaction about 60 degree, add the back and refluxed 1 hour, be cooled to 10 degree, logical ammonia 50g (99%; 2.94 mol), exothermic heat of reaction about temperature control 20 degree, was led in about 1.5 hours, filtered; Mother liquor concentrates rectifying, gets 1, and 1-encircles the third dimethanol 89.4g, GC content 98%, yield 92%; Above-mentioned reaction formula is:
Embodiment two
In the 2000L reaction kettle, drop into ethanol 900kg, dibromo neopentyl alcohol 500kg, rising temperature for dissolving is when 60 spend; Add zinc powder 135kg, added in about 3 hours, add the back and refluxed 1 hour, be cooled to 10 degree, about logical ammonia 90kg; About temperature control 20 degree, led in 2 hours, filtered, mother liquor concentrates rectifying; Get 1,1-encircles the third dimethanol finished product 180kg, GC content 98%, yield 92.7%.
Claims (8)
1. a 1-encircles the preparation method of third dimethanol, it is characterized in that organic dihalide is carried out ring-closure reaction under certain condition with reductive agent in alcoholic solvent, obtains 1; 1-encircles the solution of third dimethanol and halide salt; Logical under certain condition again ammonia carries out solid-liquid separation, filters rectifying; Obtain 1,1-encircles third dimethanol.
2. according to claim 1 a kind of 1,1-encircles the preparation method of third dimethanol, it is characterized in that organic dihalide is dichloro NSC 6366, dibromoneopentyl glycol.
3. according to claim 1 a kind of 1,1-encircles the preparation method of third dimethanol, it is characterized in that alcoholic solvent is methyl alcohol, ethanol, Virahol, propyl carbinol, preferential ethanol.
4. according to claim 1 a kind of 1,1-encircles the preparation method of third dimethanol, it is characterized in that reductive agent is iron powder, zinc powder, nickel powder, preferential zinc powder.
5. according to claim 1 or 2 or 3 or 4 described a kind of 1,1-encircles the preparation method of third dimethanol, it is characterized in that the mol ratio of organic dihalide, reductive agent and alcoholic solvent is: 1:1～1.5:10～50, preferential 1:1.2:40.
6. according to claim 4 a kind of 1,1-encircles the preparation method of third dimethanol, it is characterized in that zinc powder is 200 orders, 320 orders, 400 orders, preferential 320 orders.
7. according to one kind 1 of claim 1,1-encircles the preparation method of third dimethanol, it is characterized in that carrying out ring-closure reaction under certain condition, and promptly reduction temperature is 25～100 degree, preferential 65 degree; Reaction times is 2～8 hours, preferred 6 hours.
8. according to one kind 1 of claim 1,1-encircles the preparation method of third dimethanol, it is characterized in that logical ammonia carries out solid-liquid separation under certain condition, and promptly logical ammonia temperature is 0～50 degree, preferential 20 degree; The logical ammonia time is 1～6 hour, preferential 3 hours.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012102168633A CN102757311A (en) | 2012-06-28 | 2012-06-28 | Preparation method of 1, 1-cyclopropane dimethanol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012102168633A CN102757311A (en) | 2012-06-28 | 2012-06-28 | Preparation method of 1, 1-cyclopropane dimethanol |
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| CN102757311A true CN102757311A (en) | 2012-10-31 |
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| CN2012102168633A Pending CN102757311A (en) | 2012-06-28 | 2012-06-28 | Preparation method of 1, 1-cyclopropane dimethanol |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103058884A (en) * | 2012-12-14 | 2013-04-24 | 武汉赛狮药物化学有限公司 | Method for synthesizing 1-hydroxymethyl cyclopropyl acetonitrile |
| CN103936703A (en) * | 2013-01-17 | 2014-07-23 | 上海朴颐化学科技有限公司 | Preparation method of 5-oxaspiro[2,4]heptane-6-one and intermediate thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1921867A (en) * | 2004-02-17 | 2007-02-28 | 株式会社Lg生命科学 | Nucleoside phosphonate derivatives useful in the treatment of HIV infections |
| WO2008157658A1 (en) * | 2007-06-21 | 2008-12-24 | Protia Llc | Deuterium-enriched montelukast |
| WO2010135536A2 (en) * | 2009-05-20 | 2010-11-25 | Ardea Biosciences, Inc. | Methods of modulating uric acid levels |
| CN102206201A (en) * | 2011-01-14 | 2011-10-05 | 台州市知青化工有限公司 | Industrial production method for cyclopropyl sulfinate |
-
2012
- 2012-06-28 CN CN2012102168633A patent/CN102757311A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1921867A (en) * | 2004-02-17 | 2007-02-28 | 株式会社Lg生命科学 | Nucleoside phosphonate derivatives useful in the treatment of HIV infections |
| WO2008157658A1 (en) * | 2007-06-21 | 2008-12-24 | Protia Llc | Deuterium-enriched montelukast |
| WO2010135536A2 (en) * | 2009-05-20 | 2010-11-25 | Ardea Biosciences, Inc. | Methods of modulating uric acid levels |
| CN102206201A (en) * | 2011-01-14 | 2011-10-05 | 台州市知青化工有限公司 | Industrial production method for cyclopropyl sulfinate |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103058884A (en) * | 2012-12-14 | 2013-04-24 | 武汉赛狮药物化学有限公司 | Method for synthesizing 1-hydroxymethyl cyclopropyl acetonitrile |
| CN103936703A (en) * | 2013-01-17 | 2014-07-23 | 上海朴颐化学科技有限公司 | Preparation method of 5-oxaspiro[2,4]heptane-6-one and intermediate thereof |
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Application publication date: 20121031 |