CN100478328C - Process for preparing diazanyl ethyl acetate hydrochloride - Google Patents
Process for preparing diazanyl ethyl acetate hydrochloride Download PDFInfo
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- CN100478328C CN100478328C CNB2004100528907A CN200410052890A CN100478328C CN 100478328 C CN100478328 C CN 100478328C CN B2004100528907 A CNB2004100528907 A CN B2004100528907A CN 200410052890 A CN200410052890 A CN 200410052890A CN 100478328 C CN100478328 C CN 100478328C
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- ethyl ester
- acid ethyl
- ester hydrochloride
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Abstract
The present invention discloses preparation process of hydrazine ethyl acetate hydrochloride. Chloroacetic acid as material is first reacted with sodium hydroxide in the presence of catalyst to obtain sodium chloroacetate; sodium chloroacetate is then reacted with hydrazine hydrate under the action of sodium hydroxide to obtain intermediate; and the intermediate is finally acidified and esterified to obtain the target product hydrazine ethyl acetate hydrochloride. The preparation process of the present invention has short period, high yield, simple and safe operation and high product purity, and is suitable for industrial production.
Description
Technical field
The present invention relates to a kind of preparation method of Hydrazineacetic acid ethyl ester hydrochloride.
Background technology
Hydrazineacetic acid ethyl ester hydrochloride is a kind of important organic synthesis intermediate, can be used as the intermediate of synthetic drugs especially, has very to use widely.
English Patent GB-952400 discloses a kind of preparation method of Hydrazineacetic acid ethyl ester hydrochloride, utilize the aqueous solution of Mono Chloro Acetic Acid, sodium hydroxide and 99% hydrazine hydrate hybrid reaction to spend the night, use the concentrated hydrochloric acid acidifying, add the ethanol solution that is dissolved with dry hydrogen chloride gas, the backflow esterification, obtain Hydrazineacetic acid ethyl ester hydrochloride, yield 25%.This method is because the leaving away property of chlorion is not strong, hydrazine hydrate and the Mono Chloro Acetic Acid replacement time under alkaline condition needs very long, uses excessive sodium hydroxide in the reaction, and the α of Mono Chloro Acetic Acid molecule-chlorine atom is substituted easily, cause the hydrolysis of raw material Mono Chloro Acetic Acid, cause the yield of diazanyl sodium acetate on the low side; Adopt 99% hydrazine hydrate, cost an arm and a leg, cost is too high, has potential safety hazard, and industrial prospect is undesirable.
Helv.Chim.Acta (53; 1970; 1030-1043) preparation method of report Hydrazineacetic acid ethyl ester hydrochloride is, with the glycine is raw material, esterification under acidic conditions, obtain glycine ethyl ester hydrochloride, carry out diazotization, obtain ethyl diazoacetate, obtain the diazanyl acetate with sodium mercury-Qi reduction, acidifying then, esterification obtain Hydrazineacetic acid ethyl ester hydrochloride.This preparation method's raw material sources are extensive, but use sodium mercury-Qi reduction, and environmental pollution is serious, is unsuitable for suitability for industrialized production.
Summary of the invention
The preparation method who the purpose of this invention is to provide a kind of Hydrazineacetic acid ethyl ester hydrochloride, long to overcome in the prior art reaction times, yield is on the low side, and cost is too high, has potential safety hazard, easily the deficiency that environment is polluted.
Technical conceive of the present invention is such: be raw material with the Mono Chloro Acetic Acid, react with sodium hydroxide in the presence of catalyzer, obtain sodium chloroacetate, and then under the effect of sodium hydroxide, react with hydrazine hydrate, the intermediate that obtains carries out acidifying, and esterification promptly obtains target product of the present invention.
Method of the present invention comprises the steps:
Mono Chloro Acetic Acid, catalyzer are added in the entry, under 0-10 ℃ condition, the control pH value is 9-10, react with sodium hydroxide, obtain sodium chloroacetate solution, add hydrazine hydrate, sodium hydroxide, 15-25 ℃ was reacted 5-7 hour, the intermediate that obtains carries out acidifying, and esterification promptly obtains target product of the present invention.
According to the present invention, the mass ratio of reactant and catalyzer is 100: 1.0-2.0.
The mol ratio of reactant and sodium hydroxide is 1.0: 1.0-1.1.
Sodium chloroacetate: hydrazine hydrate: the mol ratio of sodium hydroxide is 1.0: 1.0-1.1: 1.0-1.1.
The intermediate that the present invention obtains carries out acidifying, and esterification adopts the close method of English Patent GB-952400 to obtain the target product Hydrazineacetic acid ethyl ester hydrochloride, and productive rate is more than 50%, and purity is greater than 98% (HPLC), fusing point 148-149 ℃.Results of elemental analyses is as follows:
| Element | Theoretical value (%) | Measured value (%) |
| C | 31.07 | 31.19 |
| H | 7.17 | 7.28 |
Catalyzer used in the present invention is made up of Primary Catalysts and promotor, and said Primary Catalysts is a potassiumiodide, and promotor is a Dimethylamino pyridine.
The content of hydrazine hydrate used in the present invention is 40-80wt%,
Sodium hydrate content used in the present invention is 15-35wt%.
Beneficial effect
With the synthetic Hydrazineacetic acid ethyl ester hydrochloride of method of the present invention compared with prior art, have the following advantages:
(1) adds sodium hydroxide in the reaction system at twice, weakened the alkaline environment of system, prevent that effectively α-chlorine atom in the Mono Chloro Acetic Acid molecule is by OH
-Replace, suppressed chloroacetic hydrolysis, improved yield;
(2) in reaction system, add catalyzer, accelerated diazanyl, shortened the reaction times the speed that chlorine atom in the Mono Chloro Acetic Acid replaces;
(3) adopt the hydrazine hydrate of 40%-80% to substitute 99% hydrazine hydrate, improved the security of operation.
(4) total recovery is brought up to more than 50% by 25% of bibliographical information.
Embodiment
The invention will be further described below by embodiment, but embodiment does not limit protection scope of the present invention.
Embodiment 1
In the reactor that has stirring, thermometer, dropper, add Mono Chloro Acetic Acid 94.6g (1mol), among the water 50ml, add the catalyzer that potassiumiodide 1g and 4-Dimethylamino pyridine (DMAP) 0.5g form, stir cooling down, keep temperature of reaction 0-10 ℃, pH value 9-10 splashes into 25wt% sodium hydroxide solution 160g (1mol), obtains sodium chloroacetate solution;
In sodium chloroacetate solution, stir down, slowly add 80wt% hydrazine hydrate solution 62.5g (1mol), keep temperature of reaction 15-25 ℃, splash into 15wt% sodium hydroxide solution 267g (1mol), reacted 5 hours;
The intermediate that reaction obtains, distillation dewaters, add the acidifying of 180ml concentrated hydrochloric acid, stir the back distillation and dewater, add 150ml benzene then, stirring the back distillation dewaters, add the 100ml dehydrated alcohol, stir the back distillation and dewater, in resistates, add the 400g ethanol solution that is dissolved with the 30g hydrogen chloride gas, esterification was carried out in the stirring and refluxing reaction in 2 hours, be cooled to below 40 ℃, filter the 50ml absolute ethanol washing, merging filtrate, filtrate steaming is removed ethanol, adds 100ml benzene, keeps 0 ℃ of placement to spend the night, the solid ethyl alcohol recrystallization of separating out, obtain 80g Hydrazineacetic acid ethyl ester hydrochloride white plates crystal, productive rate 51.7%, analytical results: purity 98.3% (HPLC), fusing point 148-149 ℃, results of elemental analyses:
| Element | Theoretical value (%) | Measured value (%) |
| C | 31.07 | 31.19 |
| H | 7.17 | 7.28 |
Embodiment 2
In the reactor that has stirring, thermometer, dropper, add Mono Chloro Acetic Acid 94.6g (1mol), among the water 50ml, add the catalyzer that potassiumiodide 1g and Dimethylamino pyridine (DMAP) 0.5g form, stir cooling down, keep temperature of reaction 0-10 ℃, pH value 9-10 splashes into 35wt% sodium hydroxide solution 115g (1mol), obtains sodium chloroacetate solution;
In sodium chloroacetate solution, stir down, slowly add 40wt% hydrazine hydrate solution 125g (1mol), keep temperature of reaction 15-25 ℃, splash into 15wt% sodium hydroxide solution 267g (1mol), reacted 6 hours;
The intermediate that reaction obtains, distillation dewaters, and adds the acidifying of 180ml concentrated hydrochloric acid, handles with the method for embodiment 1, esterification, ethyl alcohol recrystallization obtains 78g Hydrazineacetic acid ethyl ester hydrochloride white plates crystal, productive rate 50.5%, analytical results: fusing point 148-149 ℃, purity 98.4% (HPLC).
Claims (7)
1. the preparation method of a Hydrazineacetic acid ethyl ester hydrochloride comprises the steps:
Mono Chloro Acetic Acid, catalyzer are added in the entry, under 0-10 ℃ condition, the control pH value is 9-10, react with sodium hydroxide, obtain sodium chloroacetate solution, add hydrazine hydrate, sodium hydroxide 18-25 ℃ reaction 5-7 hour, the intermediate that obtains carries out acidifying, esterification promptly gets Hydrazineacetic acid ethyl ester hydrochloride.
2. the preparation method of Hydrazineacetic acid ethyl ester hydrochloride according to claim 1 is characterized in that, said catalyzer is made up of Primary Catalysts potassiumiodide and promotor Dimethylamino pyridine.
3. according to the preparation method of claim 1 or 2 each described Hydrazineacetic acid ethyl ester hydrochlorides, it is characterized in that the mass ratio of reactant and catalyzer is 100: 1.0-2.0.
4. the preparation method of Hydrazineacetic acid ethyl ester hydrochloride according to claim 1 is characterized in that, the mol ratio of Mono Chloro Acetic Acid and sodium hydroxide is 1.0: 1.0-1.1.
5. the preparation method of Hydrazineacetic acid ethyl ester hydrochloride according to claim 1 is characterized in that, sodium chloroacetate: hydrazine hydrate: the mol ratio of sodium hydroxide is 1.0: 1.0-1.1: 1.0-1.1.
6. the preparation method of Hydrazineacetic acid ethyl ester hydrochloride according to claim 1 is characterized in that, hydrazine hydrate content is 40-80wt%.
7. the preparation method of Hydrazineacetic acid ethyl ester hydrochloride according to claim 1 is characterized in that, sodium hydrate content is 15-35wt%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100528907A CN100478328C (en) | 2004-07-15 | 2004-07-15 | Process for preparing diazanyl ethyl acetate hydrochloride |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100528907A CN100478328C (en) | 2004-07-15 | 2004-07-15 | Process for preparing diazanyl ethyl acetate hydrochloride |
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| CN1721394A CN1721394A (en) | 2006-01-18 |
| CN100478328C true CN100478328C (en) | 2009-04-15 |
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| CNB2004100528907A Expired - Fee Related CN100478328C (en) | 2004-07-15 | 2004-07-15 | Process for preparing diazanyl ethyl acetate hydrochloride |
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| CN101003494B (en) * | 2007-01-22 | 2011-07-20 | 上海化学试剂研究所 | Method for preparing diazanyl ethyl acetate hydrochloride |
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Owner name: SINOPHARM CHEMICAL REAGENT CO., LTD. Free format text: FORMER OWNER: SHANGHAI CHEMICAL REAGENT INST. Effective date: 20110627 |
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Effective date of registration: 20110627 Address after: 200002, 1, 801 Tai Hu Road, Shanghai Patentee after: Sinopharm Chemical Reagent Co., Ltd. Address before: 200333 No. 401 True North Road, Shanghai Patentee before: Shanghai Chemical Reagent Inst. |
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