CN101823982A - Method for preparing hydrazine ethyl acetate hydrochloride - Google Patents
Method for preparing hydrazine ethyl acetate hydrochloride Download PDFInfo
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- CN101823982A CN101823982A CN200910232170A CN200910232170A CN101823982A CN 101823982 A CN101823982 A CN 101823982A CN 200910232170 A CN200910232170 A CN 200910232170A CN 200910232170 A CN200910232170 A CN 200910232170A CN 101823982 A CN101823982 A CN 101823982A
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Abstract
The invention discloses a method for preparing hydrazine ethyl acetate hydrochloride, which comprises the following steps: the first step, adding sodium hydroxide aqueous solution and hydrazine hydrate into a reaction kettle, stirring uniformly, adding chloroacetic aqueous solution into the reaction kettle after cooling, and then stirring; the second step, performing the reduced pressure distillation to the mixture, removing the water in the mixture, adding hydrochloric acid after decreasing the temperature, stirring, and removing the water in the mixture; the third step, preparing the hydrochloric alcohol solution; the fourth step, adding the hydrochloric alcohol solution prepared in the third step into the reaction product obtained in the second step, heating and refluxing; and the fifth step, after heat filtering the reaction solution obtained from the fourth step, cooling filtering, then filtering so as to obtain the crude product, and re-crystallizing the crude product in industrial alcohol to obtain the purified hydrazine ethyl acetate hydrochloride. The method of the invention is suitable for industrialization production and has the advantages of short reaction time, high yield, low cost and high production quality.
Description
Technical field
The invention belongs to the preparation method of the preparation of industrialization technology, particularly a kind of Hydrazineacetic acid ethyl ester hydrochloride of meticulous organic chemical industry's intermediate.
Background technology
Hydrazineacetic acid ethyl ester hydrochloride is a kind of important meticulous organic chemical industry's intermediate, and mainly as medicine synthetic important intermediate, scope has a wide range of applications.
English Patent GB-952400 discloses a kind of preparation method who prepares Hydrazineacetic acid ethyl ester hydrochloride.This method is mixed aqueous sodium hydroxide solution, Mono Chloro Acetic Acid and 99% hydrazine hydrate, adds hcl acidifying then, obtains Hydrazineacetic acid ethyl ester hydrochloride in adding ethanol solution of hydrogen chloride backflow esterification.This method has adopted 99% hydrazine hydrate and benzene, makes the raw materials cost height, and it is higher to produce danger coefficient.The control of this method reaction conditions is too wide in range in addition, and the yield of product is had bigger influence.
Summary of the invention
The object of the present invention is to provide a kind of preparation method of Hydrazineacetic acid ethyl ester hydrochloride, be adapted to the suitability for industrialized production path, the reaction times is short, yield is high, cost is low, good product quality, reduces the factor that influences production safety and environmental pollution.
The technical solution that realizes the object of the invention is: a kind of preparation method of Hydrazineacetic acid ethyl ester hydrochloride is characterized in that may further comprise the steps:
The first step with aqueous sodium hydroxide solution, hydrazine hydrate, joins in the reactor, stirs into homogeneous phase, opens refrigeration system and makes the reactor cooling, drips the Mono Chloro Acetic Acid aqueous solution then in reactor, dropwises the back stirring reaction;
Second step, with the mixing solutions underpressure distillation that the first step obtains, remove the water in the mixing solutions, the cooling back adds hydrochloric acid, behind the stirring reaction, with the reaction solution underpressure distillation, removes the moisture in the mixed solution;
The 3rd step fed high purity chlorination hydrogen in ethanol, the preparation ethanol solution of hydrogen chloride;
In the 4th step, the ethanol solution of hydrogen chloride that the 3rd step was obtained adds in the resulting product of second step heating reflux reaction;
The 5th step, with resulting reaction solution heat filtering postcooling filtrate of the 4th step, filter once more and can get the product crude product, with crude product recrystallization in industrial alcohol, can obtain the pure product of Hydrazineacetic acid ethyl ester hydrochloride of white plates.
The present invention compared with prior art, its remarkable advantage: adopted the hydrazine hydrate of lower concentration and reasonably temperature of reaction condition control, reduced the danger coefficient of producing, improved the general reaction yield, be applicable to suitability for industrialized production, the reaction times is short, yield is high, cost is low, good product quality, and the finished product yield is 40%, purity 〉=98.5% (HPLC), fusing point 147-148 ℃.
Embodiment
The preparation method of a kind of Hydrazineacetic acid ethyl ester hydrochloride of the present invention may further comprise the steps:
The first step with aqueous sodium hydroxide solution, hydrazine hydrate, joins in the reactor, stirs into homogeneous phase, opens refrigeration system and makes the reactor cooling, drips the Mono Chloro Acetic Acid aqueous solution then in reactor, dropwises the back stirring reaction; Above-mentioned sodium hydroxide solution is that the 20-30% aqueous solution, hydrazine hydrate are the 40%-80% hydrazine hydrate, and the Mono Chloro Acetic Acid aqueous solution of dropping is 3-5mol/L; Refrigeration system makes reactor temperature drop to 0--10 ℃; Dripping the temperature of carrying out stirring reaction behind the Mono Chloro Acetic Acid aqueous solution is 0--10 ℃, and churning time is 10-12 hour.
Second step, with the mixing solutions underpressure distillation that the first step obtains, remove the water in the mixing solutions, the cooling back adds hydrochloric acid, behind the stirring reaction, with the reaction solution underpressure distillation, removes the moisture in the mixed solution; The above-mentioned hydrochloric acid that adds is 5% industrial concentrated hydrochloric acid; Temperature is reduced to 0 ℃ after removing for the first time the water in the mixed solution, and the temperature of stirring reaction is 0 ℃, and the time of stirring reaction is 1-2 hour.
The 3rd step fed high purity chlorination hydrogen in ethanol, the preparation ethanol solution of hydrogen chloride; The content of above-mentioned ethanol solution of hydrogen chloride is 80-100g/L.
In the 4th step, the ethanol solution of hydrogen chloride that the 3rd step was obtained adds in the resulting product of second step heating reflux reaction; The temperature of above-mentioned heating reflux reaction is 80-100 ℃, and the reaction times is 5-10 hour.
The 5th step, with the 4th step resulting reaction solution heat filtering postcooling filtrate to 0 ℃, filter once more and can get the product crude product, with crude product recrystallization in industrial alcohol, can obtain the pure product of Hydrazineacetic acid ethyl ester hydrochloride of white plates.The used ethanol of above-mentioned recrystallization is the industrial alcohol of 95-98%.
Below in conjunction with embodiment the present invention is done further detailed description:
Embodiment 1
Add 125 kilograms of 40% hydrazine hydrates in the 1000L reactor, 400 kilograms of 20% aqueous sodium hydroxide solutions are cooled to 0 ℃ with reactor.Stir the Mono Chloro Acetic Acid aqueous solution 200L of Dropwise 5 mol/L down.And then under 0 ℃ of condition, stirring reaction 10 hours.
The gained reaction solution is carried out underpressure distillation, distill away 500L water after, reduce temperature in the kettle to 0 ℃.Dropwise 35 % hydrochloric acid 180L stirred 1.5 hours under 0 ℃ of condition then.The moisture in the reactor is removed in underpressure distillation then.
With concentration is in the top gained intermediate of ethanol solution of hydrogen chloride 300L adding of 80g/L, heating reflux reaction 10 hours.The reaction filtered while hot that finishes is gone out solid impurity.
Gained filtrate is filtered in the front be cooled to 25 ℃, filter to such an extent that light yellow solid is the crude product of product.Be that 98% industrial alcohol carries out recrystallization with content then, obtain 58.7 kilograms of white plates products, yield 38%, purity 98.5%, fusing point 147-148 ℃.
Embodiment 2
Add 62.5 kilograms of 80% hydrazine hydrates in the 1000L reactor, 400 kilograms of 20% aqueous sodium hydroxide solutions are cooled to reactor-5 ℃.Stir the Mono Chloro Acetic Acid aqueous solution 250L that drips 4mol/L down.And then under 0 ℃ of condition, stirring reaction 8 hours.
The gained reaction solution is carried out underpressure distillation, distill away 500L water after, reduce temperature in the kettle to 0 ℃.Dropwise 35 % hydrochloric acid 180L stirred 1.5 hours under 0 ℃ of condition then.The moisture in the reactor is removed in underpressure distillation then.
With concentration is in the top gained intermediate of ethanol solution of hydrogen chloride 250L adding of 90g/L, heating reflux reaction 8 hours.The reaction filtered while hot that finishes is gone out solid impurity.
Gained filtrate is filtered in the front be cooled to 25 ℃, filter to such an extent that light yellow solid is the crude product of product.Be that 98% industrial alcohol carries out recrystallization with content then, obtain 60.3 kilograms of white plates products, yield 39%, purity 98.5%, fusing point 147-148 ℃.
Embodiment 3
Add 62.5 kilograms of 80% hydrazine hydrates in the 1000L reactor, 270 kilograms of 30% aqueous sodium hydroxide solutions are cooled to reactor-10 ℃.Stir the Mono Chloro Acetic Acid aqueous solution 330L that drips 3mol/L down.And then under 0 ℃ of condition, stirring reaction 8 hours.
The gained reaction solution is carried out underpressure distillation, distill away 500L water after, reduce temperature in the kettle to 0 ℃.Dropwise 35 % hydrochloric acid 180L stirred 1.5 hours under 0 ℃ of condition then.The moisture in the reactor is removed in underpressure distillation then.
With concentration is in the top gained intermediate of ethanol solution of hydrogen chloride 200L adding of 100g/L, heating reflux reaction 6 hours.The reaction filtered while hot that finishes is gone out solid impurity.
Gained filtrate is filtered in the front be cooled to 25 ℃, filter to such an extent that light yellow solid is the crude product of product.Be that 98% industrial alcohol carries out recrystallization with content then, obtain 63.4 kilograms of white plates products, yield 41%, purity 98.5%, fusing point 147-148 ℃.
Claims (6)
1. the preparation method of a Hydrazineacetic acid ethyl ester hydrochloride is characterized in that, may further comprise the steps:
The first step with aqueous sodium hydroxide solution, hydrazine hydrate, joins in the reactor, stirs into homogeneous phase, opens refrigeration system and makes the reactor cooling, drips the Mono Chloro Acetic Acid aqueous solution then in reactor, dropwises the back stirring reaction;
Second step, with the mixing solutions underpressure distillation that the first step obtains, remove the water in the mixing solutions, the cooling back adds hydrochloric acid, behind the stirring reaction, with the reaction solution underpressure distillation, removes the moisture in the mixed solution;
The 3rd step fed high purity chlorination hydrogen in ethanol, the preparation ethanol solution of hydrogen chloride;
In the 4th step, the ethanol solution of hydrogen chloride that the 3rd step was obtained adds in the resulting product of second step heating reflux reaction;
The 5th step, with resulting reaction solution heat filtering postcooling filtrate of the 4th step, filter once more and can get the product crude product, with crude product recrystallization in industrial alcohol, can obtain the pure product of Hydrazineacetic acid ethyl ester hydrochloride of white plates.
2. the preparation method of Hydrazineacetic acid ethyl ester hydrochloride according to claim 1 is characterized in that, the sodium hydroxide solution in the first step is that the 20-30% aqueous solution, hydrazine hydrate are the 40%-80% hydrazine hydrate, and the Mono Chloro Acetic Acid aqueous solution of dropping is 3-5mol/L; Refrigeration system makes reactor temperature drop to 0--10 ℃; Dripping the temperature of carrying out stirring reaction behind the Mono Chloro Acetic Acid aqueous solution is 0--10 ℃, and churning time is 10-12 hour.
3. the preparation method of Hydrazineacetic acid ethyl ester hydrochloride according to claim 1 is characterized in that, the hydrochloric acid that is added in second step is 5% industrial concentrated hydrochloric acid; Temperature is reduced to 0 ℃ after removing for the first time the water in the mixed solution, and the temperature of stirring reaction is 0 ℃, and the time of stirring reaction is 1-2 hour.
4. the preparation method of Hydrazineacetic acid ethyl ester hydrochloride according to claim 1 is characterized in that, the content of ethanol solution of hydrogen chloride is 80-100g/L in the 3rd step.
5. the preparation method of Hydrazineacetic acid ethyl ester hydrochloride according to claim 1 is characterized in that, in the 4th step, the temperature of heating reflux reaction is 80-100 ℃, and the reaction times is 5-10 hour.
6. the preparation method of Hydrazineacetic acid ethyl ester hydrochloride according to claim 1 is characterized in that, in the 5th step filtrate is cooled to 0 ℃, and the used ethanol of recrystallization is the industrial alcohol of 95-98%.
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| Application Number | Priority Date | Filing Date | Title |
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| CN200910232170A CN101823982A (en) | 2009-12-02 | 2009-12-02 | Method for preparing hydrazine ethyl acetate hydrochloride |
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| CN200910232170A CN101823982A (en) | 2009-12-02 | 2009-12-02 | Method for preparing hydrazine ethyl acetate hydrochloride |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108569981A (en) * | 2018-06-07 | 2018-09-25 | 上海试四化学品有限公司 | A kind of preparation method of Tertiary butyl hydrazine hydrochloride |
| CN109111371A (en) * | 2018-09-27 | 2019-01-01 | 郑州盖科科技有限公司 | A kind of preparation method of diazanyl ethyl acetate hydrochloride |
| CN114621101A (en) * | 2020-12-11 | 2022-06-14 | 李冰坚 | Refining method of 3, 5-dimethyl-1, 2-phenylenediamine dihydrochloride |
-
2009
- 2009-12-02 CN CN200910232170A patent/CN101823982A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108569981A (en) * | 2018-06-07 | 2018-09-25 | 上海试四化学品有限公司 | A kind of preparation method of Tertiary butyl hydrazine hydrochloride |
| CN109111371A (en) * | 2018-09-27 | 2019-01-01 | 郑州盖科科技有限公司 | A kind of preparation method of diazanyl ethyl acetate hydrochloride |
| CN109111371B (en) * | 2018-09-27 | 2021-08-06 | 江西万里药业有限公司 | Preparation method of hydrazino ethyl acetate hydrochloride |
| CN114621101A (en) * | 2020-12-11 | 2022-06-14 | 李冰坚 | Refining method of 3, 5-dimethyl-1, 2-phenylenediamine dihydrochloride |
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Application publication date: 20100908 |