CN104610194A - Method for recovering promethazine oxalate from mother solution of hydrochloric acid - Google Patents
Method for recovering promethazine oxalate from mother solution of hydrochloric acid Download PDFInfo
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- CN104610194A CN104610194A CN201410595170.9A CN201410595170A CN104610194A CN 104610194 A CN104610194 A CN 104610194A CN 201410595170 A CN201410595170 A CN 201410595170A CN 104610194 A CN104610194 A CN 104610194A
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- Prior art keywords
- promethazine
- oxalate
- mother solution
- solid
- promethazine hydrochloride
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D279/10—1,4-Thiazines; Hydrogenated 1,4-thiazines
- C07D279/14—1,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems
- C07D279/18—[b, e]-condensed with two six-membered rings
- C07D279/22—[b, e]-condensed with two six-membered rings with carbon atoms directly attached to the ring nitrogen atom
- C07D279/24—[b, e]-condensed with two six-membered rings with carbon atoms directly attached to the ring nitrogen atom with hydrocarbon radicals, substituted by amino radicals, attached to the ring nitrogen atom
- C07D279/26—[b, e]-condensed with two six-membered rings with carbon atoms directly attached to the ring nitrogen atom with hydrocarbon radicals, substituted by amino radicals, attached to the ring nitrogen atom without other substituents attached to the ring system
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a method for extracting promethazine hydrochloride from a mother solution, especially to a method for recovering promethazine oxalate from the mother solution of hydrochloric acid. The method is characterized by comprising the following steps: subjecting a promethazine hydrochloride crystallization mother solution to drying by distillation so as to obtain a solid; then dissolving the obtained solid with water; after completion of dropwise addition, maintaining a temperature of about 50 DEG C for 1 h; then adding toluene for extraction after completion of temperature maintenance; then taking out a toluene layer after extraction; adding activated carbon 0.05 time by weight of the toluene layer and carrying out decolorization and filtration; subjecting the filtered toluene liquid to reduced pressure distillation until no distillate comes out; then adding methanol (four times by weight of a solid) into a concentrate; then dropwise adding an oxalic acid methanol solution 2 times by mol of the mixture obtained in the previous step; after completion of dropwise addition, carrying out reflux for 2 h; then carrying out cooling crystallization until temperature is 10 to 15 DEG C; and finally, carrying out filtering, washing and drying so as to obtain the promethazine oxalate.
Description
Technical field
The present invention relates to the extracting method of promethazine hydrochloride in a kind of mother liquor, be related specifically to a kind of method reclaiming promethazine oxalate in mother liquor of hydrochloric acid.
Reduce environmental pollution, turn waste into wealth, improve the reuse ratio of raw material.
In the mother liquor (in mother liquor, the amount of promethazine hydrochloride is about between 5% ~ 10%) of the final refining of promethazine hydrochloride, there is small part promethazine hydrochloride and partial impurities that sub-fraction do not separate out, be dissolved in acetone be solvent mother liquor in, this, the object of method is that the promethazine hydrochloride this part abandoned therefrom is taken out, and make it reach standard through process, take out with the identity of oxalate, then make promethazine hydrochloride.
Summary of the invention
Technical problem to be solved by this invention is: reduce environmental pollution, turn waste into wealth, and improves the reuse ratio of raw material.The H1 acceptor of the tissue such as unstriated muscle, capillary wall can be blocked, thus play emulative antagonistic action with histamine, still can stabilize effect by maincenter significantly, narcotic, soporific and analgesic effect can be strengthened.And medicine device body temperature and town told can be reduced.
For completing foregoing invention object, the present invention is that this is existing like this: by promethazine hydrochloride crystalline mother solution, evaporate to dryness, obtain solid (to weigh, solid is promethazine hydrochloride and impurity thereof, ), by the solid water dissolution (water of four times amount of solid) obtained, (liquid caustic soda is the liquid caustic soda of about 30% to drip liquid caustic soda again, consumption is 1.1 times of molar weights of solid, ), drip off about 50 degree insulations 1 hour, be incubated and added toluene extraction (consumption asks 2 times of weight ratios of solid) again, extract and got toluene layer, add the activated carbon decolorizing (50 degree decolouring 15 minutes) of 0.05 times of weight ratio, filter, by the toluene liquid underpressure distillation after filtration, extremely without overhead product (temperature controls at 60 degree), methyl alcohol (four times of weight ratios of solid) is added again in enriched material, rethink the methyl ethyl oxalate alcoholic solution (oxalic acid methanol ratio is 1:1) wherein dripping 2 times of molar weights, dropwise, reflux 2 hours, rear crystallisation by cooling is to temperature to 10 to 15 degree, refilter washing and drying and obtain promethazine oxalate.
Accompanying drawing explanation
Fig. 1 is technique speed second schema.
Embodiment
Embodiment 1:
3kg promethazine hydrochloride mother liquor evaporate to dryness is obtained 175g promethazine hydrochloride crude solid, 100g solid is added in the four-hole boiling flask of 1000ml, add 400g water again, stirring and dissolving, then drip the liquid caustic soda (in liquid caustic soda, the amount of alkali is the mol ratio of solids 1.1 times) of 45.7g30%.Dropwise 50 degree of insulation 1h, be incubated the complete 200g toluene that adds to extract, layering, toluene layer, 5g gac is added again in toluene liquid, 50 degree of insulations decolouring in 15 minutes, decolour complete, filter, by the toluene liquid filtered 60 degree of underpressure distillation to without overhead product, add 400g methyl alcohol again, toluene liquid enriched material is dissolved, add 112g methyl ethyl oxalate alcoholic solution (weight ratio of oxalic acid methyl alcohol is 1:1) again, back flow reaction 2 hours, be cooled to 10 ~ 15 degree again, separate out product promethazine oxalate, refilter, washing and drying obtains promethazine oxalate 93.2g, yield is 79.9%
The brief introduction of promethazine hydrochloride:
Promethazine hydrochloride (English: Promethazine, have another name called Diprazine Hydrochloride (Promethazine Hydrochloride) or promethazine hydrochloride (Phenergan)) be a kind of common cough suppressing medicine, it is a kind of antihistaminic, the competitive blocking histamine H1 acceptor of energy, to the telangiectasis caused by antihistamine, and reduce its permeability.Therefore, it is possible to calm down the cough caused because of tracheae irriate.
Can competitive blocking histamine Hl acceptor and produce antihistamine effect, to the telangiectasis caused by antihistamine, its permeability can be reduced, alleviate bronchial smooth muscle shrink caused by panting, comparatively Vena effect is strong and lasting.Because more easily entering cerebral tissue, therefore there is obvious sedative effect; The central inhibitory action of soporific, anodyne and narcotic can be strengthened; Its cholinolytic effect is also comparatively strong, and control motion sickness effect is better.For skin and mucous membrane hypersusceptibility, allergic rhinitis, asthma, food anaphylaxis, dermography and carsickness, seasick, airsick etc.
The H1 acceptor of the tissue such as unstriated muscle, capillary wall can be blocked, thus play emulative antagonistic action with histamine, still can stabilize effect by maincenter significantly, narcotic, soporific and analgesic effect can be strengthened.And can body temperature be reduced and town is told.
Here is a simple technique speed second flow process: as shown in the figure.
It is contrast that weight ratio described above and mol ratio are the solid after crystalline mother solution evaporate to dryness (promethazine hydrochloride and a small amount of impurity).
Claims (6)
1. one kind is reclaimed the method for promethazine oxalate from promethazine hydrochloride crystalline mother solution, it is characterized in that: by promethazine hydrochloride crystalline mother solution, evaporate to dryness, obtain solid, by the solid water dissolution obtained, drip off about 50 degree insulations 1 hour, be incubated and added toluene extraction again, extract and got toluene layer, add the activated carbon decolorizing of 0.05 times of weight ratio, filter, by the toluene liquid underpressure distillation after filtration, extremely without overhead product, methyl alcohol (four times of weight ratios of solid) is added again in enriched material, rethink the methyl ethyl oxalate alcoholic solution wherein dripping 2 times of molar weights, dropwise, reflux 2 hours, rear crystallisation by cooling is to temperature to 10 to 15 degree, refilter washing and drying and obtain promethazine oxalate.
2. the method reclaiming promethazine oxalate from promethazine hydrochloride crystalline mother solution according to claim 1, is characterized in that: solid is promethazine hydrochloride and impurity thereof.
3. the method reclaiming promethazine oxalate from promethazine hydrochloride crystalline mother solution according to claim 1, is characterized in that: the consumption of described water is four times of the consumption of solid.
4. the method reclaiming promethazine oxalate from promethazine hydrochloride crystalline mother solution according to claim 1, is characterized in that: described liquid caustic soda is the liquid caustic soda of about 30%, and consumption is 1.1 times of molar weights of solid.
5. the method reclaiming promethazine oxalate from promethazine hydrochloride crystalline mother solution according to claim 1, is characterized in that: by the toluene liquid underpressure distillation after filtration, to controlling at 60 degree without overhead product temperature.
6. the method reclaiming promethazine oxalate from promethazine hydrochloride crystalline mother solution according to claim 1, is characterized in that: described oxalic acid methanol ratio is 1:1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410595170.9A CN104610194B (en) | 2014-10-30 | 2014-10-30 | The method that fenazil oxalates is reclaimed in the mother liquor of hydrochloric acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410595170.9A CN104610194B (en) | 2014-10-30 | 2014-10-30 | The method that fenazil oxalates is reclaimed in the mother liquor of hydrochloric acid |
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| Publication Number | Publication Date |
|---|---|
| CN104610194A true CN104610194A (en) | 2015-05-13 |
| CN104610194B CN104610194B (en) | 2017-12-26 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201410595170.9A Active CN104610194B (en) | 2014-10-30 | 2014-10-30 | The method that fenazil oxalates is reclaimed in the mother liquor of hydrochloric acid |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113292513A (en) * | 2021-05-25 | 2021-08-24 | 常州康普药业有限公司 | Preparation method of high-purity promethazine hydrochloride |
| CN115974813A (en) * | 2022-12-20 | 2023-04-18 | 云鹏医药集团有限公司 | Synthetic method of high-purity promethazine hydrochloride |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2526118A (en) * | 1950-10-17 | Paul chabpentier | ||
| US2607773A (en) * | 1952-08-19 | Processes for preparing phenthi- | ||
| DE1181223B (en) * | 1962-07-14 | 1964-11-12 | Dresden Arzneimittel | Process for the industrial production of phenthiazine bases |
| CN102617608A (en) * | 2012-03-09 | 2012-08-01 | 常州大学 | Methods for synthesizing and separating isothipendyl serving as antihistamine medicine |
| CN102924484A (en) * | 2012-11-13 | 2013-02-13 | 常州大学 | Industrial production method of isothipendyl technical material |
-
2014
- 2014-10-30 CN CN201410595170.9A patent/CN104610194B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2526118A (en) * | 1950-10-17 | Paul chabpentier | ||
| US2607773A (en) * | 1952-08-19 | Processes for preparing phenthi- | ||
| DE1181223B (en) * | 1962-07-14 | 1964-11-12 | Dresden Arzneimittel | Process for the industrial production of phenthiazine bases |
| CN102617608A (en) * | 2012-03-09 | 2012-08-01 | 常州大学 | Methods for synthesizing and separating isothipendyl serving as antihistamine medicine |
| CN102924484A (en) * | 2012-11-13 | 2013-02-13 | 常州大学 | Industrial production method of isothipendyl technical material |
Non-Patent Citations (3)
| Title |
|---|
| WUNDERLICH HELMUT ET AL: "Chemistry of 9,9-dioxopromethazine (Prothanon)", 《PHARMAZIE》 * |
| 施仁信 等: "抗组胺药及异丙嗪的合成", 《杭州化工》 * |
| 迟文寿 等: "盐酸异丙嗪的提纯", 《中国医药工业杂质》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113292513A (en) * | 2021-05-25 | 2021-08-24 | 常州康普药业有限公司 | Preparation method of high-purity promethazine hydrochloride |
| CN113292513B (en) * | 2021-05-25 | 2022-03-25 | 常州康普药业有限公司 | Preparation method of high-purity promethazine hydrochloride |
| CN115974813A (en) * | 2022-12-20 | 2023-04-18 | 云鹏医药集团有限公司 | Synthetic method of high-purity promethazine hydrochloride |
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| CN104610194B (en) | 2017-12-26 |
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Address after: 226532 No. 10, Yuejiang Road, Changjiang town (Rugao port area), Rugao City, Nantong City, Jiangsu Province Patentee after: Jiangsu Baozhong Baoda Pharmaceutical Co.,Ltd. Address before: 226532 No. 10, Yuejiang Road, Changjiang town (Rugao port area), Rugao City, Nantong City, Jiangsu Province Patentee before: JIANGSU BAOZONG & BAODA PHARMACHEM Co.,Ltd. |