CN109651222A - A kind of process for catalytic synthesis of Aniracetam - Google Patents
A kind of process for catalytic synthesis of Aniracetam Download PDFInfo
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- CN109651222A CN109651222A CN201811573892.9A CN201811573892A CN109651222A CN 109651222 A CN109651222 A CN 109651222A CN 201811573892 A CN201811573892 A CN 201811573892A CN 109651222 A CN109651222 A CN 109651222A
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- aniracetam
- catalytic synthesis
- boric acid
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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
- C07D207/27—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
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Abstract
The invention belongs to technical field of medicine synthesis, and in particular to a kind of process for catalytic synthesis of Aniracetam.The following steps are included: organic solvent is added into reaction vessel, P-methoxybenzoic acid, 2-Pyrrolidone and boric acid class catalyst, fully reacting post-process to get Aniracetam the process for catalytic synthesis.Wherein, the catalytic effect of boric acid class catalyst is significant, itself is cheap and easy to get, to have very high economic benefit;The atom utilization of the process for catalytic synthesis is high, and by-product generated is water, no pollution to the environment;The process for catalytic synthesis is easily operated, and reaction yield and product purity are high.In short, the process for catalytic synthesis of Aniracetam provided by the present invention uses a kind of environmentally protective preparation process, and it is low in cost, particularly suitable for large-scale industrial production, therefore, have broad application prospects and good market potential.
Description
Technical field
The invention belongs to technical field of medicine synthesis, and in particular to a kind of process for catalytic synthesis of Aniracetam.
Background technique
Aniracetam (aniracetam, Aniracetam), entitled 1- (4- methoxybenzoyl the base) -2- pyrrolidines of chemistry
Ketone is a kind of gamma-lactam class cerebral function improving medicine, is clinically mainly used for treating apoplexy sequela.In addition, A Nixi
The smooth effective therapeutic agent that can be used as senile dementia, the medicine can be improved patient's intracerebral levels of acetylcholine, be conducive to choline
The transmitting of energy nerve, has the characteristics that quick, toxicity is low (northwest pharmaceutical journal, 2014,29 (1), 67-69).
The synthesis technology of Aniracetam is provided in the prior art, for example, United States Patent (USP) US4369139 reports a variety of conjunctions
At route.
For example, 2-Pyrrolidone and anisoyl chloride are in the presence of a base, Aniracetam is reacted to obtain:
For another example, P-methoxybenzoic acid is first reacted with thionyl chloride, is generated anisoyl chloride (yield 90%);So
Afterwards, anisoyl chloride is first and 4-Aminobutanoicacid is in the aqueous solution of sodium hydroxide and in triethyl group benzyl ammonium salt (TEBA)
In the presence of react, generate 4- (4- methoxybenzoyl base) aminobutyric acid (yield 69.4%), then in toluene, in dichloro Asia
Cyclization reaction occurs in the presence of sulfone, obtains Aniracetam;Said synthesis route is as follows:
For another example, 2-Pyrrolidone and triethylamine mixing, in 0~10 DEG C of dropwise addition trim,ethylchlorosilane;It finishes, reacts at room temperature
2h;Then, the dioxane solution of anisoyl chloride is added, stirs 2h at 40 DEG C, Aniracetam is made;Above-mentioned conjunction
It is as follows at route:
In addition, the method that Chinese patent application CN107840816 reports silica catalytic one-stage synthesis Aniracetam,
But wherein used catalyst amount is excessive, and isolates and purifies difficulty, therefore be not suitable for large-scale industrial production.In
Preparation method disclosed by state patent application CN107840816 is shown below:
Also, present inventor is used to prepare Aniracetam according to provided method in the prior art, passes through reality
After testing verifying repeatedly, often there is following technological deficiencies for preparation method provided by discovery in the prior art: products collection efficiency is low,
Difficulty is isolated and purified, the reaction time is longer, and environmental pollution is more serious etc..
Therefore, the novel synthesis for developing a kind of Aniracetam is the current research emphasis of this field research staff with
One of difficult point.
Summary of the invention
In order to overcome shortcomings and deficiencies existing in the prior art, the present invention is intended to provide a kind of green of Aniracetam is closed
At technique, the synthesis technology is ingenious to utilize suitable catalyst, using single step reaction up to product, to show atom utilization
Rate is high, environmentally protective, and reaction yield and product purity are high, low in cost, is conducive to the features such as realizing industrialization.
Specifically, the present invention provides a kind of process for catalytic synthesis of Aniracetam, synthetic route is as follows:
Also, the process for catalytic synthesis the following steps are included:
Organic solvent, P-methoxybenzoic acid, 2-Pyrrolidone and boric acid class catalyst are added into reaction vessel, reacts
Completely, post-processing is to get Aniracetam;
Wherein, the boric acid class catalyst is selected from following any: boric acid, boric anhydride, R-B (OH)2, Ar-B (OH)2;
Wherein, R is selected from the alkyl group of C1~C20;Ar is selected from following any: substituted or unsubstituted phenyl takes
Generation or unsubstituted naphthalene, substituted or unsubstituted azepine phenyl, substituted or unsubstituted azepine naphthalene.
Preferably, in above-mentioned process for catalytic synthesis, the structural formula of Ar is as follows:
Wherein, R1~R5It is each independently selected from: H, nitro, cyano, halogen, the halogenated alkane base of C1~C20.Wherein, halogen
Element is selected from fluorine (F), chlorine (Cl), bromine (Br), iodine (I);Wherein, halogenated alkane base is, for example, trifluoromethyl, pentafluoroethyl group, three chloroethenes
Base, bromopropyl.
It is further preferred that the boric acid class catalyst is selected from following any: benzene boron in above-mentioned process for catalytic synthesis
Acid, 4- fluorobenzoic boric acid, 3,4,5- trifluoro phenyl boric acids, 3,5- bis- (trifluoromethyl) phenyl boric acids, 3- nitrobenzene boronic acid.It is basic herein
On, the boric acid class catalyst is still more preferably from phenyl boric acid, 3,4,5- trifluoro phenyl boric acids, 3,5- bis- (trifluoromethyl) benzene boron
Any one of acid.
Preferably, in above-mentioned process for catalytic synthesis, the structural formula of Ar is as follows:
Wherein, R7~R9It is each independently selected from: H, nitro, cyano, halogen, the halogenated alkane base of C1~C20.Wherein, halogen
Element is selected from fluorine (F), chlorine (Cl), bromine (Br), iodine (I);Wherein, halogenated alkane base is, for example, trifluoromethyl, pentafluoroethyl group, three chloroethenes
Base, bromopropyl.
It is further preferred that the boric acid class catalyst is selected from following any: 4- pyrrole in above-mentioned process for catalytic synthesis
Pyridine boric acid, 2,3- bis- chloro- 4- pyridine boronic acids, 3- trifluoromethyl -4- pyridine boronic acid, 2- nitro -4- pyridine boronic acid.It is basic herein
On, the boric acid class catalyst is still more preferably 4- pyridine boronic acid.
Preferably, in above-mentioned process for catalytic synthesis, the organic solvent is selected from following any one or more combination:
Benzene, toluene, dimethylbenzene, chlorobenzene.
It is further preferred that the organic solvent is toluene in above-mentioned process for catalytic synthesis.
Preferably, in above-mentioned process for catalytic synthesis, P-methoxybenzoic acid: 2-Pyrrolidone: boric acid class catalyst
Molar ratio is 1:1:0.01~10.On this basis, it is further preferred that P-methoxybenzoic acid: 2-Pyrrolidone: boric acid class
The molar ratio of catalyst is 1:1:0.5~5.
Preferably, in above-mentioned process for catalytic synthesis, the lasting reaction time is 0.5~48 small before the post-processing
When.Also, it is worth noting that in the presence of boric acid class catalyst, reaction substrate P-methoxybenzoic acid and 2- pyrrolidines
Ketone can from 0 DEG C to heated reflux condition under reacted, preferably reacted under reflux condition.
In addition, the post-processing is those skilled in the art according to this step reaction mechanism in above-mentioned process for catalytic synthesis
The suitable post-processing that can be made with reaction condition etc., the post-processing operation are intended to remove impurity and solvent, and in certain journey
Guarantee to obtain pure product on degree.
Preferably, in above-mentioned process for catalytic synthesis, it is described post-processing the following steps are included:
Cooling, then first the solid was filtered filter cake is dissolved with ethyl alcohol, and with active carbon decoloring, after filtering while hot, cooling
Crystallization, last filtering, takes filter cake, is dried under reduced pressure.
Compared with the preparation method of published Aniracetam in the prior art, process for catalytic synthesis provided by the present invention
With following technical advantage:
Firstly, catalyst used by the process for catalytic synthesis is boric acid class catalyst, catalytic effect is significant, can be big
Amplitude improves the yield of Aniracetam, and boric acid class catalyst itself is cheap and easy to get, to have very high economic benefit.Its
Secondary, the atom utilization of the process for catalytic synthesis is high, and by-product generated is water, no pollution to the environment;The catalysis
Synthetic method is easily operated, and reaction yield and product purity are high.In short, the process for catalytic synthesis of Aniracetam of the present invention
It is low in cost using a kind of environmentally protective preparation process, particularly suitable for large-scale industrial production, therefore, have wide
Application prospect and good market potential.
Specific embodiment
The present invention is further elaborated With reference to embodiment, but the present invention is not limited to following embodiment party
Formula.
The process for catalytic synthesis of provided preferred embodiment according to the present invention, Aniracetam follows the steps below
Operation:
Organic solvent, P-methoxybenzoic acid, 2-Pyrrolidone and boric acid class catalyst are added into flask, finishes, adds
Heat reflux, the water generated with the removing of reflux dewatering device, sufficiently reacts;Cooling, then first the solid was filtered filter cake uses ethyl alcohol
Dissolution, and with active carbon decoloring, after filtering while hot, cooling crystallization, last filtering takes filter cake, is dried under reduced pressure and obtains target and produce
Object Aniracetam.
Wherein, the boric acid class catalyst is selected from following any: boric acid, boric anhydride, R-B (OH)2, Ar-B (OH)2;
Wherein, R is selected from the alkyl group of C1~C20;Ar is selected from following any: substituted or unsubstituted phenyl takes
Generation or unsubstituted naphthalene, substituted or unsubstituted azepine phenyl, substituted or unsubstituted azepine naphthalene.
In a preferred embodiment, the structural formula of Ar is as follows:
Wherein, R1~R5It is each independently selected from: H, nitro, cyano, fluorine (F), chlorine (Cl), bromine (Br), trifluoromethyl, five
Fluoro ethyl, trichloroethyl, bromopropyl.
In a further preferred embodiment, the boric acid class catalyst is selected from following any: phenyl boric acid, 4- fluorine
Phenyl boric acid, 3,4,5- trifluoro phenyl boric acids, 3,5- bis- (trifluoromethyl) phenyl boric acids, 3- nitrobenzene boronic acid.
In an embodiment still more preferably, the boric acid class catalyst is selected from following any: phenyl boric acid, and 3,
4,5- trifluoro phenyl boric acids, 3,5- bis- (trifluoromethyl) phenyl boric acids.
In a preferred embodiment, the structural formula of Ar is as follows:
Wherein, R7~R9It is each independently selected from: H, nitro, cyano, fluorine (F), chlorine (Cl), bromine (Br), trifluoromethyl, five
Fluoro ethyl, trichloroethyl, bromopropyl.
In a further preferred embodiment, the boric acid class catalyst is selected from following any: 4- pyridine boronic acid,
2,3- bis- chloro- 4- pyridine boronic acids, 3- trifluoromethyl -4- pyridine boronic acid, 2- nitro -4- pyridine boronic acid.
In an embodiment still more preferably, the boric acid class catalyst is 4- pyridine boronic acid.
In a preferred embodiment, the organic solvent is selected from following any one or more combination: benzene, toluene, and two
Toluene, chlorobenzene.
In a further preferred embodiment, the organic solvent is toluene.
In a preferred embodiment, P-methoxybenzoic acid: 2-Pyrrolidone: the molar ratio of boric acid class catalyst is 1:
1:0.01~10.
In a further preferred embodiment, P-methoxybenzoic acid: 2-Pyrrolidone: boric acid class catalyst rubs
You are than being 1:1:0.5~5.
Step in the process for catalytic synthesis of following Aniracetams is routine operation unless otherwise instructed, used anti-
Answer raw material, reagent that can obtain unless otherwise instructed from public commercial source.
Embodiment 1
Addition benzene (300ml), P-methoxybenzoic acid (30.4g), 2-Pyrrolidone (17.0g) and boric acid into flask
(1.3g), finishes, and is heated to reflux 16 hours, and the water generated with the removing of reflux dewatering device sufficiently reacts;It is cooling, it is first to filter
Solid filter cake, then dissolved with ethyl alcohol, and with active carbon decoloring, after filtering while hot, cooling crystallization, last is filtered, and takes filter cake,
It is dried under reduced pressure and obtains target product Aniracetam (30.7g), yield 70.2%.
Aniracetam is characterized as below:
1H NMR (400MHz, DMSO, TMS): δ 7.57 (2H, d, J=8.8Hz), 6.94 (2H, d, J=8.8Hz), 3.81
(3H, s), 3.79~3.75 (2H, m), 2.54~2.43 (2H, m), 2.04~1.99 (2H, m).
Embodiment 2
Addition chlorobenzene (300ml), P-methoxybenzoic acid (30.4g), 2-Pyrrolidone (17.0g) and benzene boron into flask
Sour (2.4g), finishes, is heated to reflux 16 hours, and the water generated with the removing of reflux dewatering device sufficiently reacts;It is cooling, first mistake
Solid filter cake is filtered to obtain, is then dissolved with ethyl alcohol, and with active carbon decoloring, after filtering while hot, cooling crystallization, last filtering takes filter
Cake is dried under reduced pressure and obtains target product Aniracetam (37.1g), yield 84.6%.
Embodiment 3
Addition toluene (300ml), P-methoxybenzoic acid (30.4g), 2-Pyrrolidone (17.0g) and 4- fluorine into flask
Phenyl boric acid (2.8g), finishes, and is heated to reflux 16 hours, and the water generated with the removing of reflux dewatering device sufficiently reacts;It is cooling, just
Secondary the solid was filtered filter cake, is then dissolved with ethyl alcohol, and with active carbon decoloring, after filtering while hot, cooling crystallization, and last filtering,
Filter cake is taken, is dried under reduced pressure and obtains target product Aniracetam (35.6g), yield 81.2%.
Embodiment 4
Toluene (300ml) is added into flask, P-methoxybenzoic acid (30.4g), 2-Pyrrolidone (17.0g) and 3,4,
5- trifluoro phenyl boric acid (3.5g), finishes, and is heated to reflux 16 hours, and the water generated with the removing of reflux dewatering device sufficiently reacts;It is cold
But, first the solid was filtered filter cake, is then dissolved with ethyl alcohol, and with active carbon decoloring, while hot after filtering, cooling crystallization, and last
Filtering, takes filter cake, is dried under reduced pressure and obtains target product Aniracetam (36.7g), yield 83.8%.
Embodiment 5
Toluene (300ml) is added into flask, P-methoxybenzoic acid (30.4g), 2-Pyrrolidone (17.0g) and 3,5-
Two (trifluoromethyl) phenyl boric acids (5.2g), finish, and are heated to reflux 16 hours, the water generated with the removing of reflux dewatering device, sufficiently
Reaction;Cooling, then first the solid was filtered filter cake is dissolved with ethyl alcohol, and with active carbon decoloring, cooling to analyse after filtering while hot
Crystalline substance, last filtering, takes filter cake, is dried under reduced pressure and obtains target product Aniracetam (36.8g), yield 84.1%.
Embodiment 6
Addition toluene (300ml), P-methoxybenzoic acid (30.4g), 2-Pyrrolidone (17.0g) and 3- nitre into flask
Base phenyl boric acid (3.4g), finishes, and is heated to reflux 16 hours, and the water generated with the removing of reflux dewatering device sufficiently reacts;It is cooling,
First the solid was filtered filter cake, is then dissolved with ethyl alcohol, and with active carbon decoloring, while hot after filtering, cooling crystallization, and last mistake
Filter, takes filter cake, is dried under reduced pressure and obtains target product Aniracetam (34.7g), yield 79.2%.
Embodiment 7
Addition toluene (300ml), P-methoxybenzoic acid (30.4g), 2-Pyrrolidone (17.0g) and 4- pyrrole into flask
Pyridine boric acid (2.5g), finishes, and is heated to reflux 16 hours, and the water generated with the removing of reflux dewatering device sufficiently reacts;It is cooling, just
Secondary the solid was filtered filter cake, is then dissolved with ethyl alcohol, and with active carbon decoloring, after filtering while hot, cooling crystallization, and last filtering,
Filter cake is taken, is dried under reduced pressure and obtains target product Aniracetam (30.0g), yield 68.5%.
Specific embodiments of the present invention are described in detail above, but it is merely an example, the present invention is simultaneously unlimited
It is formed on particular embodiments described above.To those skilled in the art, any couple of present invention carries out equivalent modifications and
Substitution is also all among scope of the invention.Therefore, without departing from the spirit and scope of the invention made by equal transformation and
Modification, all should be contained within the scope of the invention.
Claims (10)
1. a kind of process for catalytic synthesis of Aniracetam, which is characterized in that its synthetic route is as follows:
Also, the process for catalytic synthesis the following steps are included:
Organic solvent, P-methoxybenzoic acid, 2-Pyrrolidone and boric acid class catalyst are added into reaction vessel, has reacted
Entirely, post-processing is to get Aniracetam;
Wherein, the boric acid class catalyst is selected from following any: boric acid, boric anhydride, R-B (OH)2, Ar-B (OH)2;
Wherein, R is selected from the alkyl group of C1~C20;Ar be selected from it is following any: substituted or unsubstituted phenyl, it is substituted or
Unsubstituted naphthalene, substituted or unsubstituted azepine phenyl, substituted or unsubstituted azepine naphthalene.
2. the process for catalytic synthesis of Aniracetam according to claim 1, which is characterized in that the structural formula of Ar is as follows:
Wherein, R1~R5It is each independently selected from: H, nitro, cyano, halogen, the halogenated alkane base of C1~C20.
3. the process for catalytic synthesis of Aniracetam according to claim 2, which is characterized in that the boric acid class catalyst choosing
From following any: phenyl boric acid, 4- fluorobenzoic boric acid, 3,4,5- trifluoro phenyl boric acids, 3,5- bis- (trifluoromethyl) phenyl boric acids, 3- nitro
Phenyl boric acid.
4. the process for catalytic synthesis of Aniracetam according to claim 1, which is characterized in that the structural formula of Ar is as follows:
Wherein, R7~R9It is each independently selected from: H, nitro, cyano, halogen, the halogenated alkane base of C1~C20.
5. the process for catalytic synthesis of Aniracetam according to claim 4, which is characterized in that the boric acid class catalyst choosing
From following any: 4- pyridine boronic acid, 2,3- bis- chloro- 4- pyridine boronic acids, 3- trifluoromethyl -4- pyridine boronic acid, 2- nitro -4- pyrrole
Pyridine boric acid.
6. the process for catalytic synthesis of Aniracetam according to claim 1, which is characterized in that the organic solvent be selected from
Under any one or more combination: benzene, toluene, dimethylbenzene, chlorobenzene.
7. the process for catalytic synthesis of Aniracetam according to claim 6, which is characterized in that the organic solvent is first
Benzene.
8. the process for catalytic synthesis of Aniracetam according to claim 1, which is characterized in that P-methoxybenzoic acid: 2-
Pyrrolidones: the molar ratio of boric acid class catalyst is 1:1:0.01~10.
9. the process for catalytic synthesis of Aniracetam according to claim 1, which is characterized in that continue before the post-processing
Reaction time be 0.5~48 hour.
10. the process for catalytic synthesis of Aniracetam according to claim 1, which is characterized in that it is described post-processing include with
Lower step:
Cooling, then first the solid was filtered filter cake is dissolved with ethyl alcohol, and with active carbon decoloring, cooling to analyse after filtering while hot
Crystalline substance, last filtering, takes filter cake, is dried under reduced pressure.
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4369139A (en) * | 1978-02-10 | 1983-01-18 | Hoffmann-La Roche Inc. | 1-(P-Methoxy p-hydroxy, and p-benzyloxy benzoyl)-2-pyrrolidinones |
CN101220007A (en) * | 2008-01-16 | 2008-07-16 | 浙江耐司康药业有限公司 | Method for producing repaglinide |
CN107793325A (en) * | 2017-11-10 | 2018-03-13 | 河南省化工研究所有限责任公司 | A kind of new method for preparing synthetic capsaicin |
CN107840816A (en) * | 2017-09-04 | 2018-03-27 | 无锡济民可信山禾药业股份有限公司 | A kind of preparation method of aniracetam |
-
2018
- 2018-12-21 CN CN201811573892.9A patent/CN109651222A/en active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4369139A (en) * | 1978-02-10 | 1983-01-18 | Hoffmann-La Roche Inc. | 1-(P-Methoxy p-hydroxy, and p-benzyloxy benzoyl)-2-pyrrolidinones |
CN101220007A (en) * | 2008-01-16 | 2008-07-16 | 浙江耐司康药业有限公司 | Method for producing repaglinide |
CN107840816A (en) * | 2017-09-04 | 2018-03-27 | 无锡济民可信山禾药业股份有限公司 | A kind of preparation method of aniracetam |
CN107793325A (en) * | 2017-11-10 | 2018-03-13 | 河南省化工研究所有限责任公司 | A kind of new method for preparing synthetic capsaicin |
Non-Patent Citations (2)
Title |
---|
TOSHIKATSU MAKI ET AL.: "N-Alkyl-4-boronopyridinium Salts as Thermally Stable and Reusable Amide Condensation Catalysts", 《ORGANIC LETTERS》 * |
曾步兵 等主编: "《药用天然产物全合成:全合成路线精选》", 31 March 2016, 华东理工大学出版社 * |
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