CN103819387A - Synthesis method of aniracetam - Google Patents
Synthesis method of aniracetam Download PDFInfo
- Publication number
- CN103819387A CN103819387A CN201410046976.2A CN201410046976A CN103819387A CN 103819387 A CN103819387 A CN 103819387A CN 201410046976 A CN201410046976 A CN 201410046976A CN 103819387 A CN103819387 A CN 103819387A
- Authority
- CN
- China
- Prior art keywords
- aniracetam
- synthetic method
- triethylamine
- pyrrolidone
- alpha
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
Abstract
The invention discloses a synthesis method of aniracetam. The aniracetam is obtained by performing one-step reaction on alpha-pyrrolidone and methoxybenzoyl chloride in the existence of triethylamine serving as an acid-binding agent; after the reaction is completed, adding water into a product to remove triethylamine hydrochloride; concentrating water solution and performing alcohol extraction on the concentrated water solution to obtain the triethylamine hydrochloride. The synthesis method is safe in production and high in yield, and the economic benefit can be maximized by comprehensively utilizing byproducts.
Description
Technical field
The synthetic method that the present invention relates to a kind of aniracetam, belongs to technical field of medicine synthesis.
Technical background
Aniracetam, chemistry 1-(4-anisoyl by name)-2-Pyrrolidone, be gamma-lactam class cerebral function improving medicine, be mainly used in clinically treating cerebrovascular sequelae, also can be used for senile dementia, memory and neuroprotective system.Compare with other cerebral function improving medicines, it has the advantages that effect is strong, rapid-action, toxicity is low.
Forming intermediate about the large multiplex alpha-pyrrolidone of synthetic method of aniracetam with electrophilic reagent both at home and abroad reacts and obtains with anisoyl chloride again, so not only the yield of aniracetam is low, and used the dangerous high reagent such as sodium hydride, complex operation is not suitable for industrialized production in addition.
Summary of the invention
The object of this invention is to provide that a kind of product yield is high, production safety can fully utilize by product and realize the novel synthesis of the aniracetam of maximization of economic benefit, use the deficiency of dangerous solvent and complex operation to overcome prior art.
Implementation procedure of the present invention is as follows:
A synthetic method for aniracetam, is characterized in that: exist next step to react with anisoyl chloride at acid binding agent triethylamine alpha-pyrrolidone and obtain.After having reacted, product is added water and washes away triethylamine hydrochloride, water lotion carries out alcohol with ethanol and analyses and obtain triethylamine hydrochloride after concentrated.
In above-mentioned reaction, the mol ratio of alpha-pyrrolidone and acid binding agent triethylamine is 1:1～1:1.5, and reaction solvent is toluene, 40～110 ℃ of temperature of reaction.
From the structure of raw material of the present invention, H in alpha-pyrrolidone on lactan N demonstrates extremely strong protic under the impact of ketonic oxygen, and the Cl on acyl chlorides has extremely strong electronegativity in anisoyl chloride, as long as so the HCl system of taking out of that finds suitable acid binding agent that reaction is generated can impel reaction to carry out to positive dirction, realize the one-step synthesis of aniracetam.
Production safety of the present invention, yield are high, and can fully utilize by product and realize maximization of economic benefit.
Accompanying drawing explanation
Fig. 1 is synthetic route of the present invention;
Fig. 2 is the contrast of sample infrared spectrum and standard substance infrared spectrum.
Embodiment
Below provide specific embodiment and further set forth the present invention, but do not limit its protection domain.
Embodiment 1
The preparation of aniracetam: by 17.0g(0.2mol) alpha-pyrrolidone and 40.0mL(0.28mol) triethylamine is dissolved in 100.0mL toluene.Control temperature and be dissolved with 34.2g(0.2mol at 50 ℃ of following 40mL of dropping) toluene solution of anisoyl chloride.Drip complete water-bath and maintain the temperature at 50 ℃ of reactions 2 hours.React complete and will in reaction solution impouring 1000mL beaker, add 500mL water after being down to room temperature, stirring, suction filtration, be washed to and detect the Cl ion of water lotion and filter cake is dried after qualified, then use ethyl alcohol recrystallization, obtain white plates crystallization 37.2g(productive rate 84.7%).Fusing point, 120.2-120.8 ℃.
By above-mentioned water lotion concentrating under reduced pressure (be less than-0.05MPa of pressure) to 1/4 of original solution volume.Solution after concentrated is down to room temperature, adds the ethanol of 2 times of volumes to carry out alcohol and analyse, obtain white solid 16.5g.Fusing point, 258.7-259.6 ℃.
The structural characterization of aniracetam: ultimate analysis (C
12h
13nO
3) measured value of C, H, N and theoretical value deviation be in 0.2%.Test result is in table 1
The infrared spectrogram of the sample that as shown in Figure 1, prepared by the present invention is consistent with standard substance aniracetam collection of illustrative plates.
Whether meet the relevant criterion of bulk drug in order to detect aniracetam that the inventive method prepares, it has been carried out to content detection analysis.
Chromatographic condition: with octadecylsilane chemically bonded silica be weighting agent; Methanol-water (60:40) is moving phase; Detection wavelength is 254nm; Sample size: 20 μ l; Flow velocity: 1ml/min.
Detection method: with Betamethasone Valerate be internal standard substance, take respectively Betamethasone Valerate 0.0252g, standard substance 0.0251g, sample 0.0250g according to Chinese Pharmacopoeia by marker method with calculated by peak area, containing aniracetam 100.37%, (by dry product).
The detection method of content of triethylamine hydrochloride:
Reagent: fluorescent yellow ethanolic soln, 1g/L; Starch test solution, 10g/L; Silver Nitrate titrand, C(AgNO
3)=0.1mol/L.
Detection method: take 0.3376g sample, be dissolved in 75ml distilled water, add 8 fluorescent yellow ethanolic solns and 5ml starch test solution, be titrated to turbid solution with 0.1mol/L Silver Nitrate titrand and sport pink and be terminal.Calculating triethylamine content is 98.51%.
Claims (5)
1. a synthetic method for aniracetam, is characterized in that: exist next step to react with anisoyl chloride at acid binding agent triethylamine alpha-pyrrolidone and obtain.
2. the synthetic method of aniracetam according to claim 1, is characterized in that: the mol ratio of alpha-pyrrolidone and acid binding agent triethylamine is 1:1～1:1.5.
3. the synthetic method of aniracetam according to claim 1, is characterized in that: reaction solvent is toluene.
4. the synthetic method of aniracetam according to claim 1, is characterized in that: 40～110 ℃ of temperature of reaction.
5. the synthetic method of aniracetam according to claim 1, is characterized in that: after having reacted, product is added water and washes away triethylamine hydrochloride, water lotion carries out alcohol with ethanol and analyses and obtain triethylamine hydrochloride after concentrated.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410046976.2A CN103819387A (en) | 2014-02-11 | 2014-02-11 | Synthesis method of aniracetam |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410046976.2A CN103819387A (en) | 2014-02-11 | 2014-02-11 | Synthesis method of aniracetam |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103819387A true CN103819387A (en) | 2014-05-28 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410046976.2A Pending CN103819387A (en) | 2014-02-11 | 2014-02-11 | Synthesis method of aniracetam |
Country Status (1)
| Country | Link |
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| CN (1) | CN103819387A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL189248B1 (en) * | 1997-09-04 | 2005-07-29 | Pliva Krakow | Method of obtaining 1-(p-methoxybenzooyl)-2-pyrolydone |
| CN102558011A (en) * | 2010-12-24 | 2012-07-11 | 无锡济民可信山禾药业股份有限公司 | Novel preparation method of aniracetam |
-
2014
- 2014-02-11 CN CN201410046976.2A patent/CN103819387A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL189248B1 (en) * | 1997-09-04 | 2005-07-29 | Pliva Krakow | Method of obtaining 1-(p-methoxybenzooyl)-2-pyrolydone |
| CN102558011A (en) * | 2010-12-24 | 2012-07-11 | 无锡济民可信山禾药业股份有限公司 | Novel preparation method of aniracetam |
Non-Patent Citations (1)
| Title |
|---|
| 刘方亮等: "茴拉西坦的合成工艺研究", 《齐鲁药事》, vol. 24, no. 9, 31 December 2005 (2005-12-31), pages 558 - 559 * |
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Application publication date: 20140528 |