CN1150141A - Process for synthesizing cyclopropyl carboxylic ester - Google Patents
Process for synthesizing cyclopropyl carboxylic ester Download PDFInfo
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- CN1150141A CN1150141A CN 95113339 CN95113339A CN1150141A CN 1150141 A CN1150141 A CN 1150141A CN 95113339 CN95113339 CN 95113339 CN 95113339 A CN95113339 A CN 95113339A CN 1150141 A CN1150141 A CN 1150141A
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- cyclopropyl carboxylic
- carboxylic ester
- toluene
- ester
- sodium
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Abstract
A process for synthesizing cyclopropanecarboxylate uses gamma-chlorobutyrate as raw material, sodium alkoxide or potassium alkoxide as condensing agent and toluene as solvent, all of which react on each other at 70-130 deg.C, and features high output rate of reaction, and slight corrosion to apparatus and good thermal conductivity for sodium alkoxide.
Description
The present invention relates to the synthesis technique of cyclopropyl carboxylic ester, particularly about with γ-chloro butyric ester being the synthetic cyclopropyl carboxylic ester technology of raw material.
Cyclopropyl carboxylic ester (methyl esters, ethyl ester) is the important intermediate of synthetic drugs and agricultural chemicals, especially the important source material of pharmaceutical intermediate cyclopropylamine.Cyclopropyl carboxylic ester in the past is a raw material with gamma-butyrolactone often, at Zncl
2There is open loop down, forms through esterification, cyclization again.Afterwards, United States Patent (USP) GB1257097 had reported with γ-chloro butyric ester to be that raw material, solid sodium ethanol are that condensing agent, toluene are the synthetic cyclopropyl carboxylic ester technology of solvent.There is following shortcoming in this technology: owing to use solid sodium ethanol, make dust bigger.The easy moisture absorption hydrolysis property of sodium alkoxide produces interference to cyclization, and sodium alkoxide has very strong corrosive nature, influences the work-ing life of equipment.The sodium-chlor that produces in the process is adsorbed on the reactor wall, can have a strong impact on mass transfer, the heat transfer of reaction, and the yield of reaction is descended.For overcoming the shortcoming that exists in the above-mentioned patent, alleviate the corrosion of sodium alkoxide to equipment, improve reaction yield, we have invented a kind of novel process of synthetic cyclopropyl carboxylic ester.
The objective of the invention is to realize by following technical scheme, γ-chloro butyric ester is made in the presence of the condensing agent of 10～60% (weight) at sodium alkoxide or potassium alcoholate and alcohol, with toluene is solvent, is to react under 70～130 ℃ of conditions in normal pressure, temperature, synthetic cyclopropyl carboxylic ester.
In above-mentioned reaction, sodium alkoxide can be sodium methylate, sodium ethylate; Potassium alcoholate can be potassium methylate, potassium ethylate; Alcohol can be methyl alcohol, ethanol, and the condensing agent concentration preferable range that is made into is 15～30% (weight).The preferable range of temperature is 90～100 ℃, and the toluene solvant consumption is 1～5 times of γ-chloro butyric ester in mole number, and preferable range is 1.2～2.5 times.
In the above-mentioned reaction system,, be made into, avoided the moisture absorption hydrolysis of dust problem and sodium alkoxide or potassium alcoholate by sodium alkoxide or potassium alcoholate and alcohol because the condensing agent that adds is a liquid phase, and to the corrosion of equipment.The sodium-chlor that produces in the process, Repone K have alleviated the absorption of sodium-chlor, Repone K in the presence of a large amount of alcohol, make that mass-and heat-transfer has obtained improving greatly.Simultaneously, in reaction system, methyl alcohol that reaction produces or ethanol and toluene have formed the azeotropic composition, pass through continuous distillation process, alcohol in the reaction system is constantly steamed, carry out to generating the cyclopropyl carboxylic ester direction, constantly break molecular balance thereby promoted reaction, reaction yield is enhanced, has obtained satisfied effect.
[embodiment 1]
In having 2500 milliliters of four-hole boiling flasks of stirring, load onto addition funnel, thermometer, packed column, mix fractionation plant.Add 265 milliliters of 27.5% sodium methylate alcoholic solution, 245 grams, toluene.Dripped 136.5 gram γ-chloro butyric esters under 95 ℃ of conditions of temperature, and by fractionating system, isolate methyl alcohol-methylbenzene azeotropic thing continuously in 2 hours, 20 minutes reaction terminatings of insulation reflux after dropping finishes.Methyl alcohol-toluene the azeotrope that steams is turned back in the reactor, and solution is cooled to room temperature, and this mixture is regulated pH value with aqueous hydrochloric acid is 1～2, uses CH then
2Cl
2Extract three times.Organic layer separates on rectifier unit, collects the cyclopropyl carboxylic acid potassium ester component of 114～115 ℃ of boiling points, gets cyclopropyl carboxylic acid methyl esters 93 grams, and its ring propyl ester yield is 93.0%.[embodiment 2]
According to each step of embodiment 1, add 20% sodium methylate alcoholic solution 324 grams, temperature of reaction is 90 ℃, steaming methyl alcohol to system sodium methylate under normal pressure has certain viscosity, adds 212 milliliters of toluene again.Dripped γ-chloro methyl-butyrate 136.5 grams in 2 hours, all the other processes are with embodiment 1.Get cyclopropyl carboxylic acid methyl esters 92.5 grams, its cyclopropyl carboxylic acid methyl esters yield is 92.5%.[embodiment 3]
According to each step of embodiment 1,159 milliliters of sodium ethylate alcoholic solution 434 grams of adding 18%, toluene.Drip γ-chloro ethyl butyrate 150.5 grams, temperature of reaction is 80 ℃.After reaction finishes, get cyclopropyl carboxylic acid ethyl ester 99.5 grams, its cyclopropyl carboxylic acid ethyl ester yield is 87.3%.[embodiment 4]
According to each step of embodiment 1,475 milliliters of potassium ethylate alcoholic solution 735 grams of adding 12%, toluene.Drip γ-chloro methyl-butyrate 136.5 grams, temperature of reaction is 75 ℃.After reaction finishes, get cyclopropyl carboxylic acid methyl esters 85 grams, its cyclopropyl carboxylic acid methyl esters yield is 85%.[embodiment 5]
According to each step of embodiment 1,106 milliliters of potassium methylate alcoholic solution 127 grams of adding 55%, toluene.Drip γ-chloro ethyl butyrate 150.5 grams, temperature of reaction is 115 ℃.After reaction finishes, get cyclopropyl carboxylic acid ethyl ester 102.6 grams, it encircles the third carboxylic ester ethyl ester yield is 90%.
Claims (6)
1. process for synthesizing cyclopropyl carboxylic ester, with γ-chloro butyric ester is that raw material, sodium alkoxide or potassium alcoholate alcoholic solution are made condensing agent, toluene is made solvent, under 70～130 ℃ of conditions of temperature, react, it is characterized in that condensing agent is that its concentration is 10～60% (weight) by sodium alkoxide or potassium alcoholate and the pure solvent that is made into.
2. according to the described process for synthesizing cyclopropyl carboxylic ester of claim 1, it is characterized in that alcohol is methyl alcohol, ethanol; Sodium alkoxide is sodium methylate, sodium ethylate; Potassium alcoholate is potassium methylate, potassium ethylate.
3. according to the described process for synthesizing cyclopropyl carboxylic ester of claim 1, it is characterized in that temperature is 90～100 ℃.
4. according to the described process for synthesizing cyclopropyl carboxylic ester of claim 1, it is characterized in that condensing agent concentration is 15～30% (weight).
5. according to the described process for synthesizing cyclopropyl carboxylic ester of claim 1, it is characterized in that the consumption of toluene is 1～5: 1 in mole number toluene: γ-chloro butyric ester.
6. according to the described process for synthesizing cyclopropyl carboxylic ester of claim 1, it is characterized in that the consumption of toluene is 1.2～2.5: 1 in mole number toluene: γ-chloro butyric ester.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN95113339A CN1050597C (en) | 1995-11-15 | 1995-11-15 | Process for synthesizing cyclopropyl carboxylic ester |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN95113339A CN1050597C (en) | 1995-11-15 | 1995-11-15 | Process for synthesizing cyclopropyl carboxylic ester |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1150141A true CN1150141A (en) | 1997-05-21 |
| CN1050597C CN1050597C (en) | 2000-03-22 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN95113339A Expired - Fee Related CN1050597C (en) | 1995-11-15 | 1995-11-15 | Process for synthesizing cyclopropyl carboxylic ester |
Country Status (1)
| Country | Link |
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| CN (1) | CN1050597C (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104817453A (en) * | 2015-05-14 | 2015-08-05 | 大丰跃龙化学有限公司 | Novel method for synthesizing cyclopropanecarboxylic acid |
| CN106278890A (en) * | 2016-08-16 | 2017-01-04 | 西安近代化学研究所 | A kind of synthetic method of 1 (1 halogenated cyclopropyl) formic acid ester compound |
| CN106854157A (en) * | 2016-11-30 | 2017-06-16 | 浙江大学 | The method for synthesizing cyclopropane ester in low-alcohols solubility solvent |
| CN111499508A (en) * | 2020-05-06 | 2020-08-07 | 山东国邦药业有限公司 | Preparation method of methyl cyclopropanecarboxylate |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES370147A1 (en) * | 1968-08-29 | 1971-04-01 | Gulf Research Development Co | A procedure to manufacture ciclopropilamin. (Machine-translation by Google Translate, not legally binding) |
| DE4222497A1 (en) * | 1992-07-09 | 1994-01-13 | Huels Chemische Werke Ag | Process for the production of chlorine-free methyl cyclopropanecarboxylate |
-
1995
- 1995-11-15 CN CN95113339A patent/CN1050597C/en not_active Expired - Fee Related
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104817453A (en) * | 2015-05-14 | 2015-08-05 | 大丰跃龙化学有限公司 | Novel method for synthesizing cyclopropanecarboxylic acid |
| CN104817453B (en) * | 2015-05-14 | 2016-08-31 | 大丰跃龙化学有限公司 | A kind of method synthesizing cyclopropanecarboxylic acid |
| CN106278890A (en) * | 2016-08-16 | 2017-01-04 | 西安近代化学研究所 | A kind of synthetic method of 1 (1 halogenated cyclopropyl) formic acid ester compound |
| CN106854157A (en) * | 2016-11-30 | 2017-06-16 | 浙江大学 | The method for synthesizing cyclopropane ester in low-alcohols solubility solvent |
| CN106854157B (en) * | 2016-11-30 | 2019-06-21 | 浙江大学 | The method of cyclopropane ester is synthesized in low-alcohols solubility solvent |
| CN111499508A (en) * | 2020-05-06 | 2020-08-07 | 山东国邦药业有限公司 | Preparation method of methyl cyclopropanecarboxylate |
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| Publication number | Publication date |
|---|---|
| CN1050597C (en) | 2000-03-22 |
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Granted publication date: 20000322 Termination date: 20091215 |