CN102766050A - Method for synthesizing dimethyl fumarate - Google Patents
Method for synthesizing dimethyl fumarate Download PDFInfo
- Publication number
- CN102766050A CN102766050A CN201210284628XA CN201210284628A CN102766050A CN 102766050 A CN102766050 A CN 102766050A CN 201210284628X A CN201210284628X A CN 201210284628XA CN 201210284628 A CN201210284628 A CN 201210284628A CN 102766050 A CN102766050 A CN 102766050A
- Authority
- CN
- China
- Prior art keywords
- dimethyl fumarate
- maleic anhydride
- reaction
- compound method
- dmf
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for synthesizing dimethyl fumarate. The method includes: adding maleic anhydride and methanol into a four-opening bottle provided with a motor stirrer, a condenser pipe and a thermometer with material quantity ratio as methanol: maleic anhydride=(5-25):1 for stirring, adding (0.4-1.2)g of catalyst stannic chloride into each mol of maleic anhydride, hanging a small silk sealed bag containing MgSO4 powder at the position of each bottle opening, leading temperature to rise to 50-60 DEG C for backflow reaction for 2.5-4.5 h, adding reaction liquor obtained after reaction into cold water for suction filtration to obtain dimethyl formamide (DMF) coarse products, and performing recrystallization by aid of methanol to obtain pure DMF. Compared with the traditional synthetic method of dimethyl fumarate, the method for synthesizing dimethyl fumarate is simple in synthesizing route, and the obtained product dimethyl fumarate is higher in purity.
Description
Technical field
The invention belongs to the synthetic field of organic chemistry, be specifically related to a kind of compound method of dimethyl fumarate.
Background technology
Mildew-resistant has become one of problem of current extensive concern.Dimethyl fumarate (DMF) can be applicable to the mildew-resistant of multiple industries such as food, feed as a kind of novel mould inhibitor.It is a white crystal, and 102～105 ℃ of fusing points are dissolved in ethanol, chloroform; Be slightly soluble in water; Can distil under the normal temperature,, have the advantages that low toxicity, efficient, long action time, chemicalstability are good, use pH wide ranges, broad-spectrum antimicrobial light and thermally stable; Have insecticidal activity concurrently, also have and tag and fumigation action.
In recent years, tin tetrachloride received many investigators' concern as a kind of esterifying catalyst efficiently.
Summary of the invention
The invention provides a kind of compound method of dimethyl fumarate, is Primary Catalysts with the stannic chloride pentahydrate, and maleic anhydride, methyl alcohol are raw material, adopts the synthetic dimethyl fumarate of " one kettle way " catalysis.
In the four-hole bottle that installs electric mixer, prolong, TM; According to amount of substance than methyl alcohol: maleic anhydride=5～25:1 adds maleic anhydride and methyl alcohol stirring; Add 0.4～1.2g catalyzer stannic chloride pentahydrate according to every mol maleic anhydride, MgSO is housed in the bottle mouth position suspension
4Behind the silk sealing pouch of powder, be warmed up to 50～60 ℃ of back flow reaction 2.5～4.5h, reaction adds reaction solution in the cold water after finishing, and suction filtration obtains the thick product of DMF, obtains pure DMF with recrystallizing methanol.
Particular methanol is 15:1 with the amount of substance ratio of maleic anhydride.
Preferred catalyst stannic chloride pentahydrate consumption is that every mol maleic anhydride adds 1.0g.
Preferably be warmed up to 50～60 ℃ of back flow reaction 3h.
Compare with the compound method of traditional dimethyl fumarate, compound method synthetic route of the present invention is simple, and products obtained therefrom dimethyl fumarate purity is higher.
Embodiment
Below in conjunction with embodiment the compound method of dimethyl fumarate of the present invention is set forth in detail, thereby protection scope of the present invention is made more explicit defining so that advantage of the present invention and characteristic can be easier to it will be appreciated by those skilled in the art that.
The raw material reagent that the present invention is used: maleic anhydride (analytical pure, Dongxing, Shenyang City chemical reagent work); Methyl alcohol (analytical pure, the Shenyang City newly changes chemical reagent work); Stannic chloride pentahydrate (CP, Beijing dicyclo chemical reagent factory).
Embodiment 1
In the four-hole bottle that installs electric mixer, prolong, TM, add 1mol maleic anhydride and 5mol methyl alcohol and stir, add the 0.4g stannic chloride pentahydrate, in the bottle mouth position suspension MgSO is housed
4Behind the silk sealing pouch of powder, be warmed up to 50～60 ℃ of back flow reaction 2.5h, reaction adds reaction solution in the cold water after finishing, and suction filtration obtains the thick product of DMF, obtains pure DMF with recrystallizing methanol, productive rate 82.5%.
Embodiment 2
In the four-hole bottle that installs electric mixer, prolong, TM, add 1mol maleic anhydride and 25mol methyl alcohol and stir, add the 1.2g stannic chloride pentahydrate, in the bottle mouth position suspension MgSO is housed
4Behind the silk sealing pouch of powder, be warmed up to 50～60 ℃ of back flow reaction 4.5h, reaction adds reaction solution in the cold water after finishing, and suction filtration obtains the thick product of DMF, obtains pure DMF with recrystallizing methanol, productive rate 84.6%.
Embodiment 3
In the four-hole bottle that installs electric mixer, prolong, TM, add 1mol maleic anhydride and 15mol methyl alcohol and stir, add the 1.0g stannic chloride pentahydrate, in the bottle mouth position suspension MgSO is housed
4Behind the silk sealing pouch of powder, be warmed up to 50～60 ℃ of back flow reaction 3h, reaction adds reaction solution in the cold water after finishing, and suction filtration obtains the thick product of DMF, obtains pure DMF with recrystallizing methanol, productive rate 88.7%.
Compare with the compound method of traditional dimethyl fumarate, compound method synthetic route of the present invention is simple, and products obtained therefrom dimethyl fumarate purity is higher.
Claims (4)
1. the compound method of a dimethyl fumarate, it may further comprise the steps:
In the four-hole bottle that installs electric mixer, prolong, TM; According to amount of substance than methyl alcohol: maleic anhydride=5～25:1 adds maleic anhydride and methyl alcohol stirring; Add 0.4～1.2g catalyzer stannic chloride pentahydrate according to every mol maleic anhydride, MgSO is housed in the bottle mouth position suspension
4Behind the silk sealing pouch of powder, be warmed up to 50～60 ℃ of back flow reaction 2.5～4.5h, reaction adds reaction solution in the cold water after finishing, and suction filtration obtains the thick product of DMF, obtains pure DMF with recrystallizing methanol.
2. the compound method of dimethyl fumarate according to claim 1 is characterized in that: the amount of substance of methyl alcohol and maleic anhydride is than being 15:1.
3. the compound method of dimethyl fumarate according to claim 1 is characterized in that: catalyzer stannic chloride pentahydrate consumption is that every mol maleic anhydride adds 1.0g.
4. the compound method of dimethyl fumarate according to claim 1 is characterized in that: be warmed up to 50～60 ℃ of back flow reaction 3h.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210284628XA CN102766050A (en) | 2012-08-10 | 2012-08-10 | Method for synthesizing dimethyl fumarate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210284628XA CN102766050A (en) | 2012-08-10 | 2012-08-10 | Method for synthesizing dimethyl fumarate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102766050A true CN102766050A (en) | 2012-11-07 |
Family
ID=47093661
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210284628XA Pending CN102766050A (en) | 2012-08-10 | 2012-08-10 | Method for synthesizing dimethyl fumarate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102766050A (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104098471A (en) * | 2013-04-03 | 2014-10-15 | 南京卡文迪许生物工程技术有限公司 | Dimethyl fumarate polymorph, preparation method thereof and pharmaceutical composition |
| CN104483344A (en) * | 2015-01-07 | 2015-04-01 | 重庆民泰香料化工有限责任公司 | Fast judging method for DMF of mildew preventive |
| WO2015044853A3 (en) * | 2013-09-25 | 2015-06-11 | Glenmark Pharmaceuticals Limited; Glenmark Generics Limited | Process for preparation of dimethyl fumarate |
| CN104761453A (en) * | 2015-04-22 | 2015-07-08 | 河南中帅医药科技股份有限公司 | Dimethyl fumarate crystal form and preparation method thereof |
| WO2016001093A1 (en) * | 2014-07-03 | 2016-01-07 | Synthon B.V. | Process for making microcrystalline dimethyl fumarate |
| US9422226B2 (en) | 2011-06-08 | 2016-08-23 | Biogen Ma Inc. | Process for preparing high purity and crystalline dimethyl fumarate |
| EP3097075A4 (en) * | 2014-01-24 | 2017-06-21 | Shilpa Medicare Limited | Process for preparation of dimethyl-(e)-butenedioate |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102432464A (en) * | 2011-12-14 | 2012-05-02 | 费近峰 | Continuous production process for dimethyl fumarate |
-
2012
- 2012-08-10 CN CN201210284628XA patent/CN102766050A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102432464A (en) * | 2011-12-14 | 2012-05-02 | 费近峰 | Continuous production process for dimethyl fumarate |
Non-Patent Citations (2)
| Title |
|---|
| 孙悦等: "《食品防霉剂富马酸二甲酯的合成》", 《北方园艺》, no. 7, 15 April 2012 (2012-04-15), pages 173 - 174 * |
| 肖新荣等: "《四氯化锡催化合成富马酸二甲酯》", 《精细化工中间体》, vol. 34, no. 4, 31 December 2004 (2004-12-31) * |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9422226B2 (en) | 2011-06-08 | 2016-08-23 | Biogen Ma Inc. | Process for preparing high purity and crystalline dimethyl fumarate |
| CN104098471A (en) * | 2013-04-03 | 2014-10-15 | 南京卡文迪许生物工程技术有限公司 | Dimethyl fumarate polymorph, preparation method thereof and pharmaceutical composition |
| WO2015044853A3 (en) * | 2013-09-25 | 2015-06-11 | Glenmark Pharmaceuticals Limited; Glenmark Generics Limited | Process for preparation of dimethyl fumarate |
| US9840456B2 (en) | 2013-09-25 | 2017-12-12 | Glenmark Pharmaceuticals Limited | Process for preparation of dimethyl fumarate |
| EP3097075A4 (en) * | 2014-01-24 | 2017-06-21 | Shilpa Medicare Limited | Process for preparation of dimethyl-(e)-butenedioate |
| WO2016001093A1 (en) * | 2014-07-03 | 2016-01-07 | Synthon B.V. | Process for making microcrystalline dimethyl fumarate |
| CN104483344A (en) * | 2015-01-07 | 2015-04-01 | 重庆民泰香料化工有限责任公司 | Fast judging method for DMF of mildew preventive |
| CN104483344B (en) * | 2015-01-07 | 2017-05-10 | 重庆民泰香料化工有限责任公司 | Fast judging method for DMF of mildew preventive |
| CN104761453A (en) * | 2015-04-22 | 2015-07-08 | 河南中帅医药科技股份有限公司 | Dimethyl fumarate crystal form and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102766050A (en) | Method for synthesizing dimethyl fumarate | |
| CN101367760B (en) | Synthesis of 2-chlorine apellagrin | |
| CN102816122B (en) | Preparation method of pyrimethanil | |
| CN103724279B (en) | One step to form the loop prepares the convenient synthetic method of 2-methyl-4-amino-5-amino methylpyrimidine | |
| CN105254575A (en) | Synthetic method for sulfadiazine | |
| CN107056756A (en) | A kind of method for preparing high-purity Losartan | |
| CN109503380A (en) | The synthetic method of 4- alkoxy acetoacetates | |
| CN100537552C (en) | Method for preparing Repaglinide | |
| CN107473948A (en) | A kind of synthetic method that the pentanone of 3,5 dichloro 2 is prepared by ethyl acetoacetate | |
| CN101367767B (en) | Room temperature solvent-free synthesis of 3,4-dihydropyrimidine-2-ketone | |
| CN101362752B (en) | Synthesis method of lamivudine intermediate | |
| CN104672180A (en) | Chiral preparation method of [(1S)-3-methyl-1-[[(2R)-2-methylepoxyethyl]carbonyl]butyl]tert-butyl carbamate | |
| CN103102327A (en) | Preparation method of rubber accelerator DZ (N,N-Dicyclohexyl-2-benzothiazolsulfene amide) | |
| CN103073520B (en) | Method for synthesizing 2-phenyl benzothiazole and derivative thereof | |
| CN103360307B (en) | Preparation method of 5-chloro-2,4-dihydroxypyridine | |
| CN107674079B (en) | Synthesis method of ibrutinib | |
| CN105061137A (en) | Synthetic method for 4, 4'-bis(chloromethyl) biphenyl | |
| CN101735117B (en) | Preparation method of o-aminosulfonyl-benzoyl hydrazine | |
| CN106632001A (en) | Preparation method of 4-(bromoacetyl) pyridine hydrobromide | |
| CN103833530A (en) | Preparation method of organic intermediate 3-phenoxyl-1, 2-propylene glycol | |
| CN107954853A (en) | A kind of preparation method of important intermediate 2,4 difluorobenzene formic acid | |
| CN109111371B (en) | Preparation method of hydrazino ethyl acetate hydrochloride | |
| CN102603777A (en) | Preparation method of nysted reagent | |
| CN102584803A (en) | Preparation method of high-content quizalofop-P-tefuryl | |
| CN104387259A (en) | Method for preparing 2,4,5-trifluorophenylacetic acid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20121107 |