CN1134930A - Salicylic dextrogyric pseudoephedrine and synthesis method thereof - Google Patents
Salicylic dextrogyric pseudoephedrine and synthesis method thereof Download PDFInfo
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- CN1134930A CN1134930A CN 96103008 CN96103008A CN1134930A CN 1134930 A CN1134930 A CN 1134930A CN 96103008 CN96103008 CN 96103008 CN 96103008 A CN96103008 A CN 96103008A CN 1134930 A CN1134930 A CN 1134930A
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- pseudoephedrine
- dextrogyric
- salicylic
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Abstract
This pseudo-ephedrine salicylate drug's chemical name is 1S, 2S-alpha (1-methylamino)ethyl] benzene methanol salicylate, its chemical formula is C17 H21 NO4, molecular weight 303.34. d-pseudo ephedrine and salicylic acid or aspirin as raw material to synthesize d-ephedrine salicylate. It possesses the action of asprin and the action of d-pseudo ephedrine as well, such as, allay fever, ease pain, anti-inflammation etc. It is low in toxicity and less in side effect.
Description
The present invention relates to medicine and synthetic method thereof, is a kind of salicylic dextrogyric pseudoephedrine and synthetic method thereof.
At present, stronger because salicylic acidity is bigger to the pungency of stomach, therefore can not take orally; Thereby limited its medicinal application scope aspect antipyretic-antalgic, anti-inflammatory.In order to overcome salicylic medicinal pair of effect, worked out salicylic various derivative again, as Asprin etc., but Asprin still has certain acidity.
The objective of the invention is to propose a kind of salicylic dextrogyric pseudoephedrine and synthetic method thereof.
The molecular formula of this salicylic dextrogyric pseudoephedrine is C
17H
21NO
4, its molecular weight is 303.34, chemical name 1S, and 2S-α-[(1-methylamino-) ethyl] phenylcarbinol salicylate, its structural formula is:
Wherein, recording fusing point with X-4 type micro melting point apparatus is 130 to 134 ℃, indicates polarimeter to measure specific rotation automatically with WZZ-1 and is [α]
D 20+ 40 °, thermometer is not calibrated; Water-soluble or ethanol or non-polar organic solvent are insoluble to ether, are slightly soluble in acetone isopolarity organic solvent, show neutral in the aqueous solution, bitter, and outward appearance is the off-white color xln.
Through Institute of Analysis of Lanzhou University the structure of this salicylic dextrogyric pseudoephedrine is measured, according to the comprehensive analysis and judgement of the spectroscopic data of infrared spectra, proton nmr spectra and carbon-13 spectrums, ultimate analysis and model compound etc., this salicylic dextrogyric pseudoephedrine is the salt that pseudoephedrine and two kinds of compositions of Whitfield's ointment form.Concrete argument See Attachment 1 is the structure determination report of Institute of Analysis of Lanzhou University to this salicylic dextrogyric pseudoephedrine.The building-up reactions formula of this salicylic dextrogyric pseudoephedrine has two kinds: a kind of is to be raw material with dextrorotation pseudoephedrine and Asprin, and its reaction formula is:
Another kind is to be raw material with dextrorotation pseudoephedrine and Whitfield's ointment, and its reaction formula is:
It is embodiment that this salicylic dextrogyric pseudoephedrine has following synthetic method:
One of synthetic method is carried out according to the following steps: the dextrorotation pseudoephedrine is mixed by 1: 1 to 1: 1.2 mol ratio with Asprin, the water that adds 5 to 10 times of dextrorotation pseudoephedrine weight, room temperature was placed 7 to 30 days, boil off moisture content with vacuum method then, the ether that adds 10 to 15 times of dextrorotation pseudoephedrine weight, fully stirring makes it separate out precipitation, carry out solid-liquid separation then, 40 to 60 ℃ water or the dehydrated alcohol of isolated solid with 5 to 10 times of amount dextrorotation pseudoephedrine weight fully dissolved, under room temperature or 5 to 15 ℃ of temperature, carry out crystallization then, obtain salicylic dextrogyric pseudoephedrine;
In the aforesaid method, the mixture to dextrorotation pseudoephedrine, Asprin and water in 40 to 80 ℃ water was incubated and places 5 to 10 hours, just can finish reaction.
Two of synthetic method is carried out according to the following steps: the dextrorotation pseudoephedrine is mixed by 1: 1 to 1: 1.5 weight ratio with Whitfield's ointment, the ether that adds 10 to 15 times of dextrorotation pseudoephedrine weight, (follow the tracks of the existence of dextrorotation pseudoephedrine with thin layer chromatography) till at room temperature being stirred well to dextrorotation pseudoephedrine complete reaction, carry out suction filtration and make solid-liquid separation, 40 to 60 ℃ water or the dehydrated alcohol of isolated solid with 5 to 10 times of dextrorotation pseudoephedrine weight fully dissolved, under room temperature or 5 to 15 ℃ of temperature, carry out crystallization then, obtain salicylic dextrogyric pseudoephedrine.
Three of synthetic method is carried out according to the following steps: the dextrorotation pseudoephedrine is mixed by 1: 1 to 1: 1.5 weight ratio with Whitfield's ointment, the solvent that adds 5 to 10 times of dextrorotation pseudoephedrine weight, solvent is a dehydrated alcohol, be heated to 40 to 60 ℃ and be incubated then, when waiting not have solid, steam ethanol with vacuum method, the ether that adds 5 to 10 times of solid weights again, thorough mixing was also placed 30 to 60 minutes, carry out suction filtration then and make solid-liquid separation, 40 to 60 ℃ water or the dehydrated alcohol of isolated solid with 5 to 10 times of amount dextrorotation pseudoephedrine weight fully dissolved, under room temperature or 5 to 15 ℃ of temperature, carry out crystallization then, obtain salicylic dextrogyric pseudoephedrine.
Four of synthetic method is carried out according to the following steps: the dextrorotation pseudoephedrine is mixed by 1: 1 to 1: 1.5 weight ratio with Whitfield's ointment, the solvent that adds 4 to 8 times of dextrorotation pseudoephedrine weight, solvent is a chloroform, in 40 to 60 ℃ water, be incubated to solid all till the dissolving, when cooling the temperature to room temperature then, the anhydrous diethyl ether that slowly adds 2 to 5 times of chloroform volumes, placed again 30 minutes to 60 minutes Deng separating out post precipitation, carry out suction filtration then and make solid-liquid separation, 40 to 60 ℃ water or the dehydrated alcohol of isolated solid with 5 to 10 times of amount dextrorotation pseudoephedrine weight fully dissolved, under room temperature or 5 to 15 ℃ of temperature, carry out crystallization then, obtain salicylic dextrogyric pseudoephedrine;
In the aforesaid method, when in 40 to 60 ℃ water, being incubated till solid all dissolves, after can earlier chloroform being steamed, cool the temperature to room temperature again.
In method three or four, solvent also can be acetone or DMSO or THF.
In aforesaid method, raw material Whitfield's ointment, Asprin, dextrorotation pseudoephedrine, water, ether, dehydrated alcohol, chloroform, acetone, DMSO, THF adopt the desired raw material of pharmaceutical industries standard.
In aforesaid method, if the solid of separating has color, 40 to 60 ℃ water or the dehydrated alcohol of isolated solid with 5 to 10 times of amount dextrorotation pseudoephedrine weight fully can be dissolved, the activated carbon that adds 0.5% to 3% solid weight decolours, placed 5 to 10 minutes down at 40 to 60 ℃, the filtering activated carbon carries out crystallization under room temperature or 5 to 15 ℃ of temperature then, obtains salicylic dextrogyric pseudoephedrine.
In aforesaid method, more thorough for what unreacted raw material was removed, isolated solid washed with the ether of 0.5 to 2 times of dextrorotation pseudoephedrine weight again carry out suction filtration and make solid-liquid separation, and then carry out recrystallization with the crystallization method in the aforesaid method.
To the salicylic dextrogyric pseudoephedrine that obtains with above-mentioned synthetic method, teaching and research room carries out effect experiment by the Xinjiang Medical College pharmacology, and every experiment is as follows:
Acute toxicity test: the Kunming mouse that animal provides for Xinjiang endemy institute, adopting the Bliss method to measure medium lethal dose is LD
50, detailed step sees that the effect experiment report is an annex two; The result is LD
50=718.7 ± 0.031mg/Kg belongs to the hypotoxicity medicine, because of working as LD
50Belong to the hypotoxicity medicine during＞500mg/Kg.
Anti-inflammatory action experiment: Wistar rat and NIH mouse that animal provides for Xinjiang endemy institute, one is the influence that p-Xylol causes the NIH mice ear, it two is influence to pedal swelling due to the Wistar rat carrageenan, its result is that this salicylic dextrogyric pseudoephedrine anti-inflammatory action is suitable with Asprin, and detailed step sees that the effect experiment report is an annex two.
The analgesic activity experiment: one is the influence that Dichlorodiphenyl Acetate brings out the reaction of NIH mouse writhing, it two is influence to NIH mouse foot sole of the foot thorn Severe Pain territory, its result is that this salicylic dextrogyric pseudoephedrine analgesic activity is suitable with Asprin, and detailed step sees that the effect experiment report is an annex two.
The effect of gastric irritation effect payable at sight is tested: select for use healthy Wistar rat to experimentize, its result has only about 1/5th of Asprin, detailed step for the effect of paying of this salicylic dextrogyric pseudoephedrine and sees that the effect experiment report is an annex two.
This salicylic dextrogyric pseudoephedrine promptly has the effect of Asprin aspect drug effect, the effect of dextrorotation pseudoephedrine is arranged again, not only have analgesic, analgesia, anti-inflammatory action, and can optionally shrink upper respiratory tract blood vessel, the elimination nasopharynx laryngeal edema, and the toxicity of this salicylic dextrogyric pseudoephedrine is low, the effect of paying is less, the hormesis of stomach had only about 1/5th of Asprin, be a kind of very good, anti-flu of no drowsiness effect, anti-rhinitis medicament, to remove the irritated caused headache of flu, the phenomenon of having a stuffy nose, drop tears, sneeze has unique effects.The synthesis step of this salicylic dextrogyric pseudoephedrine is simple, the yield height, and abundant raw material is easy to get, and production cost is low, and environmental pollution is light in synthetic production process.
Claims (10)
1. a salicylic dextrogyric pseudoephedrine is characterized in that molecular formula is C
17H
21NO
4, its molecular weight is 303.34, chemical name 1S, 2S-α 1 (1-methylamino-) ethyl] and the phenylcarbinol salicylate, its structural formula is:
Wherein, fusing point is 130 to 134 ℃, and specific rotation is [α]
D 20+ 40 °, water-soluble or ethanol is insoluble to ether, shows neutral in the aqueous solution, bitter.
2. the synthetic method of a salicylic dextrogyric pseudoephedrine, it is characterized in that carrying out according to the following steps: the dextrorotation pseudoephedrine is mixed by 1: 1 to 1: 1.2 mol ratio with Asprin, the water that adds 5 to 10 times of dextrorotation pseudoephedrine weight, room temperature was placed 7 to 30 days, boil off moisture content with vacuum method then, the ether that adds 10 to 15 times of dextrorotation pseudoephedrine weight, fully stirring makes it separate out precipitation, carry out solid-liquid separation then, 40 to 60 ℃ water or the dehydrated alcohol of isolated solid with 5 to 10 times of amount dextrorotation pseudoephedrine weight fully dissolved, under room temperature or 5 to 15 ℃ of temperature, carry out crystallization then, obtain salicylic dextrogyric pseudoephedrine.
3. the synthetic method of salicylic dextrogyric pseudoephedrine according to claim 2 is characterized in that the mixture to dextrorotation pseudoephedrine, Asprin and water was incubated and places 5 to 10 hours in 40 to 80 ℃ water.
4. the synthetic method of a salicylic dextrogyric pseudoephedrine, it is characterized in that carrying out according to the following steps: the dextrorotation pseudoephedrine is mixed by 1: 1 to 1: 1.5 weight ratio with Whitfield's ointment, the ether that adds 10 to 15 times of dextrorotation pseudoephedrine weight, at room temperature be stirred well to till the dextrorotation pseudoephedrine complete reaction, carry out suction filtration and make solid-liquid separation, 40 to 60 ℃ water or the dehydrated alcohol of isolated solid with 5 to 10 times of amount dextrorotation pseudoephedrine weight fully dissolved, under room temperature or 5 to 15 ℃ of temperature, carry out crystallization then, obtain salicylic dextrogyric pseudoephedrine.
5. the synthetic method of a salicylic dextrogyric pseudoephedrine, it is characterized in that carrying out according to the following steps: the dextrorotation pseudoephedrine is mixed by 1: 1 to 1: 1.5 weight ratio with Whitfield's ointment, the solvent that adds 5 to 10 times of dextrorotation pseudoephedrine weight, solvent is a dehydrated alcohol, be incubated 40 to 60 ℃ and be incubated then, when waiting not have solid, steam ethanol with vacuum method, the ether that adds 5 to 10 times of solid weights again, thorough mixing was also placed 30 to 60 minutes, carry out suction filtration then and make solid-liquid separation, 40 to 60 ℃ water or the dehydrated alcohol of isolated solid with 5 to 10 times of amount dextrorotation pseudoephedrine weight fully dissolved, under room temperature or 5 to 15 ℃ of temperature, carry out crystallization then, obtain salicylic dextrogyric pseudoephedrine.
6. the synthetic method of a salicylic dextrogyric pseudoephedrine, it is characterized in that carrying out according to the following steps: the dextrorotation pseudoephedrine is mixed by 1: 1 to 1: 1.5 weight ratio with Whitfield's ointment, the solvent that adds 4 to 8 times of dextrorotation pseudoephedrine weight, solvent is a chloroform, in 40 to 60 ℃ water, be incubated to solid all till the dissolving, when cooling the temperature to room temperature then, the anhydrous diethyl ether that slowly adds 2 to 5 times of chloroform volumes, placed again 30 minutes to 60 minutes Deng separating out post precipitation, carry out suction filtration then and make solid-liquid separation, 40 to 60 ℃ water or the dehydrated alcohol of isolated solid with 5 to 10 times of amount dextrorotation pseudoephedrine weight fully dissolved, under room temperature or 5 to 15 ℃ of temperature, carry out crystallization then, obtain salicylic dextrogyric pseudoephedrine.
7. the synthetic method of salicylic dextrogyric pseudoephedrine according to claim 6 is characterized in that being incubated in 40 to 60 ℃ water to solid all till the dissolving, after chloroform is steamed, cools the temperature to room temperature again.
8. according to the synthetic method of claim 5 or 6 or 7 described salicylic dextrogyric pseudoephedrines, it is characterized in that solvent is acetone or DMSO or THF.
9. according to the synthetic method of claim 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 described salicylic dextrogyric pseudoephedrines, it is characterized in that 40 to 60 ℃ water or the dehydrated alcohol of isolated solid with 5 to 10 times of amount dextrorotation pseudoephedrine weight fully dissolved, the activated carbon that adds 0.5% to 3% solid weight decolours, placed 5 to 10 minutes down at 40 to 60 ℃, filtering activated carbon then, under room temperature or 5 to 15 ℃ of temperature, carry out crystallization, obtain salicylic dextrogyric pseudoephedrine.
10. according to the synthetic method of claim 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 described salicylic dextrogyric pseudoephedrines, it is characterized in that isolated solid washed with the ether of 0.5 to 2 times of dextrorotation pseudoephedrine weight and carry out suction filtration and make solid-liquid separation, and then carry out recrystallization.
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| CN96103008A CN1067981C (en) | 1996-02-21 | 1996-02-21 | Salicylic dextrogyric pseudoephedrine and synthesis method thereof |
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|---|---|---|---|
| CN96103008A CN1067981C (en) | 1996-02-21 | 1996-02-21 | Salicylic dextrogyric pseudoephedrine and synthesis method thereof |
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| CN1067981C CN1067981C (en) | 2001-07-04 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1101467C (en) * | 1998-12-04 | 2003-02-12 | 中国科学院化工冶金研究所 | Ephedra cell ZHJ-25 CGMCC No.0359 and its induction method |
| CN112198274A (en) * | 2020-11-02 | 2021-01-08 | 北京市理化分析测试中心 | Method for detecting pseudoephedrine hydrochloride in paracetamol and pseudoephedrine hydrochloride tablet |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2104684A1 (en) * | 1991-03-04 | 1992-09-05 | Mahdi B. Fawzi | Salts/ion pairs of non-steroidal anti-inflammatory drugs in various dosage forms |
-
1996
- 1996-02-21 CN CN96103008A patent/CN1067981C/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1101467C (en) * | 1998-12-04 | 2003-02-12 | 中国科学院化工冶金研究所 | Ephedra cell ZHJ-25 CGMCC No.0359 and its induction method |
| CN112198274A (en) * | 2020-11-02 | 2021-01-08 | 北京市理化分析测试中心 | Method for detecting pseudoephedrine hydrochloride in paracetamol and pseudoephedrine hydrochloride tablet |
| CN112198274B (en) * | 2020-11-02 | 2022-04-05 | 北京市理化分析测试中心 | Method for detecting pseudoephedrine hydrochloride in paracetamol and pseudoephedrine hydrochloride tablet |
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| CN1067981C (en) | 2001-07-04 |
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Address after: 830049 the Xinjiang Uygur Autonomous Region Urumqi City Xinyi Road No. 8 Patentee after: Xinjiang Medicine University Address before: Department of pharmacy No. 1 medical college the Xinjiang Uygur Autonomous Region 830049 Urumqi City Xinyi Road Patentee before: Xinjiang Medical College |
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Granted publication date: 20010704 Termination date: 20100221 |