CN105646217A - Preparation method of diethyl n-butylmalonate - Google Patents
Preparation method of diethyl n-butylmalonate Download PDFInfo
- Publication number
- CN105646217A CN105646217A CN201610102343.8A CN201610102343A CN105646217A CN 105646217 A CN105646217 A CN 105646217A CN 201610102343 A CN201610102343 A CN 201610102343A CN 105646217 A CN105646217 A CN 105646217A
- Authority
- CN
- China
- Prior art keywords
- sodium
- diethyl
- preparation
- diethyl malonate
- butylmalonate
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
Abstract
The invention discloses a preparation method of diethyl n-butylmalonate. The preparation method comprises following steps as follows: 1), ethanol and sodium react to generate sodium ethoxide; 2), diethyl malonate is added to sodium ethoxide obtained in the step 1), and diethyl malonate sodium salt is generated; 3), bromobutane is added to the diethyl malonate sodium salt obtained in the step 2), and diethyl n-butylmalonate is generated through reaction. According to the preparation method of diethyl n-butylmalonate, ethanol, sodium, diethyl malonate and bromobutane are taken as raw materials, a catalyst is not required, prepared diethyl n-butylmalonate has high yield and high purity and meets the drug quality standard, and meanwhile, the preparation cost is reduced.
Description
Technical field
The present invention relates to diethyl butylmalonate field, the preparation method particularly relating to a kind of diethyl butylmalonate.
Background technology
Diethyl butylmalonate is a kind of important Organic Chemicals, and it is widely used in dyestuff, spice, pesticide and medicine and other fields, and particularly in medicine synthesizes, it is a kind of important synthetic intermediate, and its structural formula is as follows:It is mainly as the intermediate of antipyretic analgesic Phenylbutazone. Currently the preparation of diethyl butylmalonate typically requires the diethyl butylmalonate adopting catalyst just can obtain high yield, and the use of catalyst will necessarily increase the preparation cost of diethyl butylmalonate.
Summary of the invention
In view of this, the preparation method that it is an object of the invention to provide a kind of diethyl butylmalonate, reduce the cost of diethyl butylmalonate, and there is high yield.
To achieve these goals, the technical scheme is that
The preparation method of a kind of diethyl butylmalonate, comprises the following steps:
1) ethanol and sodium reaction generate Sodium ethylate;
2) to step 1) Sodium ethylate that obtains adds diethyl malonate, generate diethyl malonate sodium salt;
3) to step 2) the diethyl malonate sodium salt that obtains adds n-butyl bromide, reaction generates diethyl butylmalonate.
Preferably, step 1) particularly as follows: first pass into N in the reactor fill ethanol2, then sodium is joined in dehydrated alcohol, at 70��73 DEG C, after reaction 12��15h, stop passing into N2; Heating temperatures to 80��120 DEG C is sloughed ethanol simultaneously and obtain Sodium ethylate; The ratio of described sodium and the amount of substance of described ethanol is 1:4��5.
Preferably, step 2) particularly as follows: after passing into cooling water 30��60min in the cooling water jecket of reactor, then pass into N2, it is slowly added dropwise diethyl malonate afterwards, stops after dripping passing into cooling water and N2, obtain diethyl malonate sodium salt.
Preferably, step 3) particularly as follows: to step 2) the diethyl malonate sodium salt that obtains adds n-butyl bromide, and at 76��84 DEG C, it is incubated 0.5��1h, filters, rectification obtains diethyl butylmalonate.
Preferably, described in be filtered into and first reduce the temperature to less than 60 DEG C, add water and aqueous sodium bromide sloughed; Add toluene to be sloughed by unnecessary water; Again through distillation, toluene is sloughed.
Preferably, the amount of substance of described sodium, described diethyl malonate and described n-butyl bromide is than for 4:3.75:4.3.
Can be seen that from technique scheme, the preparation method of diethyl butylmalonate provided by the invention, with ethanol, sodium, diethyl malonate and n-butyl bromide for raw material, without adopting catalyst, the diethyl butylmalonate yield prepared is high, purity is high, meet medicine quality standard, reduce cost of manufacture simultaneously.
Detailed description of the invention
In order to further appreciate that the present invention, below in conjunction with embodiment, the preferred embodiments of the invention are described, but it is to be understood that these describe simply as to further illustrate the features and advantages of the present invention rather than the restriction to patent requirements of the present invention.
The preparation method of a kind of diethyl butylmalonate, comprises the following steps:
1) ethanol and sodium reaction generate Sodium ethylate;
2) to step 1) Sodium ethylate that obtains adds diethyl malonate, generate diethyl malonate sodium salt;
3) to step 2) the diethyl malonate sodium salt that obtains adds n-butyl bromide, reaction generates diethyl butylmalonate.
The present invention is with ethanol, sodium, diethyl malonate and n-butyl bromide for raw material, it is not necessary to catalyst, reduces the cost of diethyl butylmalonate, and the yield of diethyl butylmalonate is high, purity is high, meets medicine quality standard.
Wherein, the reaction equation of the reaction generation Sodium ethylate of ethanol and sodium is as follows:
Na+C2H5OH��C2H5ONa+H2����
In an embodiment of the present invention, being prepared by N of Sodium ethylate2Prepare under atmosphere, it is to avoid the problem that Sodium ethylate easily decomposes, burns. Wherein, the reaction temperature of ethanol and sodium is 30��40 DEG C, and the response time is 30��60min, has reacted and has namely stopped passing into N2; Owing to Sodium ethylate existing too much ethanol, affect the reaction of Sodium ethylate and diethyl malonate, it is therefore desirable to sloughed by the ethanol in alcohol sodium solution. In an embodiment of the present invention, adopt the way of distillation to remove ethanol, namely obtain Sodium ethylate; Vapo(u)rizing temperature is 80��120 DEG C.
In the present invention, Sodium ethylate and diethyl malonate react generate diethyl malonate sodium salt reaction equation as follows:
In an embodiment of the present invention, step 1) in adopt the way of distillation to slough ethanol and obtain Sodium ethylate, the temperature in reactor will necessarily be made to raise, and temperature in reactor too high time, the generation of by-product can be caused, it is thus desirable to pass into cooling water in the cooling water jecket of reactor, namely needed first to lead to cold water intaking 10��30min before adding diethyl malonate, make the temperature in reactor lower; Pass into N more simultaneously2, it is slowly added dropwise diethyl malonate, stops after dripping passing into cooling water and N2, thus obtaining diethyl malonate sodium salt.
In the present invention, diethyl malonate sodium salt and n-butyl bromide react generate diethyl butylmalonate reaction equation as follows:
In an embodiment of the present invention, adding n-butyl bromide, and be incubated 0.5��1h at 76��84 DEG C in diethyl malonate sodium salt, filtration, rectification obtain diethyl butylmalonate; When wherein temperature is 76��84 DEG C, it is possible to reflux so that diethyl malonate sodium salt and n-butyl bromide can fully be reacted.
It should be noted that in an embodiment of the present invention, it is filtered into and first reduces the temperature to less than 60 DEG C, add water and aqueous sodium bromide is sloughed; Add toluene to be sloughed by unnecessary water; Again through distillation, toluene is sloughed; Diethyl butylmalonate is obtained again through rectification.
By the diethyl butylmalonate adopting technique scheme to prepare, just can obtain the diethyl butylmalonate of high yield without catalyst, and purity is good, meets medicine quality standard, and side-product sodium bromide can be recycled, it is to avoid environmental pollution.
In order to further illustrate the present invention, provide the preparation method of diethyl butylmalonate to be described in detail the present invention below in conjunction with embodiment, but they can not be interpreted as limiting the scope of the present invention.
Raw material used in following example is commercially available.
Embodiment 1
N is passed in the reactor fill 900g ethanol2, 90g sodium is joined in dehydrated alcohol, at 73 DEG C, after reaction 12h, stops passing into N2; Heating temperatures to 80 DEG C is sloughed ethanol simultaneously and obtain Sodium ethylate; In the cooling water jecket of reactor, pass into cooling water 30min again, then pass into N2, and in Sodium ethylate, drip 600g diethyl malonate lentamente, stop after dripping passing into cooling water and N2, obtain diethyl malonate sodium salt; In dropping 590g n-butyl bromide, and being incubated 30min at 76 DEG C, filtration, rectification obtain diethyl butylmalonate.
The productivity of the diethyl butylmalonate that the present embodiment prepares is 76.42%, and purity is 99.57%.
Embodiment 2
N is passed in the reactor fill 1200g ethanol2, 96g sodium is joined in dehydrated alcohol, at 73 DEG C, after reaction 14h, stops passing into N2; Heating temperatures to 80 DEG C is sloughed ethanol simultaneously and obtain Sodium ethylate; In the cooling water jecket of reactor, pass into cooling water 60min again, then pass into N2, and in Sodium ethylate, drip 600g diethyl malonate lentamente, stop after dripping passing into cooling water and N2, obtain diethyl malonate sodium salt; In dropping 600g n-butyl bromide, and being incubated 45min at 80 DEG C, filtration, rectification obtain diethyl butylmalonate.
The productivity of the diethyl butylmalonate that the present embodiment prepares is 76.48%, and purity is 99.69%.
Embodiment 3
N is passed in the reactor fill 1122g ethanol2, 84g sodium is joined in dehydrated alcohol, at 72 DEG C, after reaction 15h, stops passing into N2; Heating temperatures to 80 DEG C is sloughed ethanol simultaneously and obtain Sodium ethylate; In the cooling water jecket of reactor, pass into cooling water 45min again, then pass into N2, and in Sodium ethylate, drip 600g diethyl malonate lentamente, stop after dripping passing into cooling water and N2, obtain diethyl malonate sodium salt; In dropping 588g n-butyl bromide, and being incubated 60min at 84 DEG C, filtration, rectification obtain diethyl butylmalonate.
The productivity of the diethyl butylmalonate that the present embodiment prepares is 76.44%, and purity is 99.56%.
Embodiment 4
N is passed in the reactor fill 1100g ethanol2, 92g sodium is joined in dehydrated alcohol, at 73 DEG C, after reaction 15h, stops passing into N2; Heating temperatures to 80 DEG C is sloughed ethanol simultaneously and obtain Sodium ethylate; In the cooling water jecket of reactor, pass into cooling water 60min again, then pass into N2, and in Sodium ethylate, drip 605g diethyl malonate lentamente, stop after dripping passing into cooling water and N2, obtain diethyl malonate sodium salt; In dropping 596g n-butyl bromide, and being incubated 60min at 82 DEG C, filtration, rectification obtain diethyl butylmalonate.
The productivity of the diethyl butylmalonate that the present embodiment prepares is 76.45%, and purity is 99.61%.
Embodiment 5
N is passed in the reactor fill 1300g ethanol2, 91g sodium is joined in dehydrated alcohol, at 73 DEG C, after reaction 14h, stops passing into N2; Heating temperatures to 80 DEG C is sloughed ethanol simultaneously and obtain Sodium ethylate; In the cooling water jecket of reactor, pass into cooling water 60min again, then pass into N2, and in Sodium ethylate, drip 600g diethyl malonate lentamente, stop after dripping passing into cooling water and N2, obtain diethyl malonate sodium salt;In dropping 600g n-butyl bromide, and being incubated 60min at 78 DEG C, filtration, rectification obtain diethyl butylmalonate.
The productivity of the diethyl butylmalonate that the present embodiment prepares is 76.45%, and purity is 99.52%.
Above the preparation method of a kind of diethyl butylmalonate provided by the invention is described in detail; principles of the invention and embodiment are set forth by specific case used herein; the explanation of above example is only intended to help to understand method and the core concept thereof of the present invention; should be understood that; for those skilled in the art; under the premise without departing from the principles of the invention; the present invention can also carry out some improvement and modification, and these improve and modify in the protection domain also falling into the claims in the present invention.
Claims (6)
1. the preparation method of a diethyl butylmalonate, it is characterised in that comprise the following steps:
1) ethanol and sodium reaction generate Sodium ethylate;
2) to step 1) Sodium ethylate that obtains adds diethyl malonate, generate diethyl malonate sodium salt;
3) to step 2) the diethyl malonate sodium salt that obtains adds n-butyl bromide, reaction generates normal-butyl propylmalonic acid diethylester.
2. preparation method as claimed in claim 1, it is characterised in that step 1) particularly as follows: first pass into N in the reactor fill ethanol2, then sodium is joined in dehydrated alcohol, at 70��73 DEG C, after reaction 12-15h, stop passing into N2; Heating temperatures to 80��120 DEG C is sloughed ethanol simultaneously and obtain Sodium ethylate; The ratio of described sodium and the amount of substance of described ethanol is 1:4��5.
3. preparation method as claimed in claim 1, it is characterised in that step 2) particularly as follows: after passing into cooling water 30��60min in the cooling water jecket of reactor, then pass into N2, it is slowly added dropwise diethyl malonate afterwards, stops after dripping passing into cooling water and N2, obtain diethyl malonate sodium salt.
4. preparation method as claimed in claim 1, it is characterized in that, step 3) particularly as follows: to step 2) the diethyl malonate sodium salt that obtains adds n-butyl bromide, and at 76��84 DEG C, it is incubated 0.5��1h, filters, rectification obtains diethyl butylmalonate.
5. preparation method as claimed in claim 4, it is characterised in that described in be filtered into and first reduce the temperature to less than 60 DEG C, add water and aqueous sodium bromide sloughed; Add toluene to be sloughed by unnecessary water; Again through distillation, toluene is sloughed.
6. the preparation method as described in any one of Claims 1 to 5, it is characterised in that the amount of substance of described sodium, described diethyl malonate and described n-butyl bromide is than for 4:3.75:4.3.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610102343.8A CN105646217A (en) | 2016-02-24 | 2016-02-24 | Preparation method of diethyl n-butylmalonate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610102343.8A CN105646217A (en) | 2016-02-24 | 2016-02-24 | Preparation method of diethyl n-butylmalonate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105646217A true CN105646217A (en) | 2016-06-08 |
Family
ID=56489662
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610102343.8A Pending CN105646217A (en) | 2016-02-24 | 2016-02-24 | Preparation method of diethyl n-butylmalonate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105646217A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115433081A (en) * | 2022-07-22 | 2022-12-06 | 北京悦康科创医药科技股份有限公司 | Preparation method of dipropylmalonic acid diethyl ester |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103183612A (en) * | 2011-12-30 | 2013-07-03 | 北大方正集团有限公司 | Dipropylmalonic acid diester preparation method |
-
2016
- 2016-02-24 CN CN201610102343.8A patent/CN105646217A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103183612A (en) * | 2011-12-30 | 2013-07-03 | 北大方正集团有限公司 | Dipropylmalonic acid diester preparation method |
Non-Patent Citations (3)
| Title |
|---|
| 孙昌俊等主编: "《药物合成反应理论与实践》", 31 May 2007 * |
| 王炳祥主编: "《有机化学实验》", 31 August 2004 * |
| 黎钢主编: "《精细化工常用中间体手册》", 31 January 2009 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115433081A (en) * | 2022-07-22 | 2022-12-06 | 北京悦康科创医药科技股份有限公司 | Preparation method of dipropylmalonic acid diethyl ester |
| CN115433081B (en) * | 2022-07-22 | 2024-04-26 | 北京悦康科创医药科技股份有限公司 | Preparation method of diethyl dipropylmalonate |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103420801B (en) | Method for preparing pentafluorophenol | |
| CN102887817A (en) | Novel method for synthesizing 2,3,4,5,6-pentafluorophenol | |
| CN105418395A (en) | One-pot synthesis method for 4-aryl methylene-2,6-disubstituted-2,5-cyclohexadiene-1-one | |
| CN105646217A (en) | Preparation method of diethyl n-butylmalonate | |
| CN103193608A (en) | Method for preparing dimethoxy benzaldehyde from veratrole | |
| CN102020572A (en) | Method for preparing tetrabutyl ammonium bromide | |
| CN103694136B (en) | The method of divinyl one-step synthesis method adiponitrile | |
| CN106188117B (en) | A kind of synthetic method of alkoxy carbonyl group phenyl boric acid | |
| CN105348254A (en) | Method for preparing 1,3-propane sultone | |
| CN105646214A (en) | Preparation method of diethyl ethylisopentylmalonate | |
| CN102432594B (en) | Method for preparing 1-(3-hydroxymethylpyridine-2-yl)-2-phenyl-4-methyl piperazine serving as medicinal intermediate | |
| CN103145525B (en) | Synthesis method of 1 - fluoro - 3 - [2 - (trans- 4 - alkyl cyclohexyl) ethyl] benzene | |
| CN105254611A (en) | Preparation method for benzothiophene-2-carboxylic acid | |
| CN101973862B (en) | Method for preparing 3,3'-bis (trifluoromethyl) benzophenone | |
| CN103772177A (en) | Preparation method of p-methoxyacetophenone | |
| CN102643188B (en) | Method for preparing 5-bromovalerate | |
| CN104311432A (en) | Method for preparing important midbody (1R,2S)-2-(3,4-difluorinated phenyl) cyclopropylamine of ticagrelor | |
| CN102503920A (en) | Method for preparing 7-hydroxyl-4-methyl coumarin | |
| CN102311325B (en) | Method for preparing prasugrel intermediate cyclopropyl-2-fluorine benzyl ketone | |
| CN103012094A (en) | Synthesis method of ionone-type spice intermediate products | |
| CN103588638B (en) | A kind of 4-(benzene butoxy) benzoic synthetic method | |
| CN101781165B (en) | Method for synthesizing dicyclohexyl o-fluoroethylbenzene liquid crystal compound | |
| CN105016979A (en) | Synthesis method of 4-n-alkyl substituted phenol | |
| CN102557939B (en) | Method for preparing ethyl acetoacetate | |
| CN106892806B (en) | Method for preparing 1-p-methylphenyl-4, 4, 4-trifluoro-1, 3-butanedione |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB02 | Change of applicant information | ||
| CB02 | Change of applicant information |
Address after: 261000 two kilometers east of Hou Zhendong, Cha Cha village, North Shouguang, Weifang, Shandong Applicant after: Weifang crystalline chemical Limited by Share Ltd Address before: 261000 two kilometers east of Hou Zhendong, Cha Cha village, North Shouguang, Weifang, Shandong Applicant before: WEIFANG JINGRUN CHEMICAL CO., LTD. |
|
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20160608 |