CN108912002A - The preparation method of aminomethylbenzoic acid - Google Patents
The preparation method of aminomethylbenzoic acid Download PDFInfo
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- CN108912002A CN108912002A CN201810677509.8A CN201810677509A CN108912002A CN 108912002 A CN108912002 A CN 108912002A CN 201810677509 A CN201810677509 A CN 201810677509A CN 108912002 A CN108912002 A CN 108912002A
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- aminomethylbenzoic acid
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- acid
- aminomethylbenzoic
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/04—Formation of amino groups in compounds containing carboxyl groups
- C07C227/06—Formation of amino groups in compounds containing carboxyl groups by addition or substitution reactions, without increasing the number of carbon atoms in the carbon skeleton of the acid
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Abstract
The invention discloses a kind of preparation methods of aminomethylbenzoic acid, belong to technical field of medicine synthesis, including：In methyl alcohol by the dissolution of 4- chloromethyl benzoic acid, mixed solution is obtained；Concentrated ammonia liquor is added into mixed solution, controlled at 40~80 DEG C, it is reacted in the reaction vessel, so that 4- chloromethyl benzoic acid is changed into Aminomethylbenzoic Acid, obtain aminomethylbenzoic acid after separation of solid and liquid, the preparation method of aminomethylbenzoic acid of the present invention, using methanol as solvent, addition catalyst is not needed, so that it may the Aminomethylbenzoic Acid of high-purity be made, and the by-product of reaction process is less, product yield is higher；The usage amount of ammonium hydroxide of the present invention is greatly reduced, and reduces the cost recovery of ammonium hydroxide, and alleviates pollution of the ammonia to environment；The present invention is not high to equipment requirement, cost is relatively low, simple production process, can be with large-scale promotion application.
Description
Technical field
The invention belongs to technical field of medicine synthesis, and in particular to a kind of preparation method of aminomethylbenzoic acid.
Background technique
The chemical name of aminomethylbenzoic acid is Aminomethylbenzoic Acid (Aminomethylbenzoic Acid), and molecular formula is
C8H9NO2, molecular weight 151.16, it is a kind of potent haemostatic medicament, tool that aminomethylbenzoic acid, which is both drug and medicine intermediate,
There is antifibrinolytic anastalsis, haemostatic effect is significant, and toxic side effect is slight, and drug safety is high, is suitable for more
The treatment of the bleeding of seed type；It is the key intermediate for preparing another haemostatic medicament-tranexamic acid, market again simultaneously
Demand is big, is a kind of high value added product.Currently, the preparation method of industrial most common aminomethylbenzoic acid is：With 4- chloromethane
Yl benzoic acid is raw material, and ammonium carbonate is added as catalyst, neutralizes to obtain product through ammonification, acidification, removal impurity and ammonium hydroxide, by
In catalyst need to be added, cause its by-product more, preparation process is complicated, and product yield is lower.
Summary of the invention
The purpose of the present invention is to provide a kind of simple processes, the preparation method of the higher aminomethylbenzoic acid of product yield.
The preparation method of this aminomethylbenzoic acid provided by the invention, including：
In methyl alcohol by the dissolution of 4- chloromethyl benzoic acid, mixed solution is obtained；
Concentrated ammonia liquor is added into mixed solution, controlled at 40~80 DEG C, is reacted in the reaction vessel, 4- chlorine is made
Methyl benzoic acid is changed into Aminomethylbenzoic Acid, and the aminomethylbenzoic acid is obtained after separation of solid and liquid.
Chemical reaction process of the invention is：
Preferably, the reaction temperature is 60~80 DEG C.
Preferably, the mass percent of the ammonium hydroxide is 25%~28%.
Preferably, the molar ratio of the ammonia and 4- chloromethyl benzoic acid is (4~5):1.
Preferably, the mass ratio of the methanol and reactant is (10~30):1, the reactant is 4- chloromethylbenzene first
Acid and ammonia.
Preferably, the reaction time is 1~5h.
Preferably, the operating pressure of the reaction vessel is 0.1~0.5Mpa.
Preferably, the material of the reaction vessel is enamel or titanium, has good chemical stability and metal strong
Degree.
The present invention is using methanol as solvent, and in reaction process, the Aminomethylbenzoic Acid of generation does not dissolve in methanol, thus
It efficiently separates product with reactant, good impetus is played to above-mentioned chemical reaction, promote the progress of reaction, by
In Aminomethylbenzoic Acid from solution Precipitation, can avoid its reacted with other raw materials generate by-product, obtain high-purity
Aminomethylbenzoic acid product.
Compared with prior art, advantageous effects of the invention：
(1) preparation method of aminomethylbenzoic acid of the present invention does not need addition catalyst, just using methanol as solvent
The Aminomethylbenzoic Acid of high-purity can be made, and the by-product of reaction process is less, product yield is higher.
(2) usage amount of the preparation method of aminomethylbenzoic acid of the present invention, ammonium hydroxide is greatly reduced, and reduces returning for ammonium hydroxide
Harvest sheet, and alleviate pollution of the ammonia to environment.
(3) preparation method of aminomethylbenzoic acid of the present invention, it is not high to equipment requirement, cost is relatively low, simple production process,
It can be with large-scale promotion application.
Detailed description of the invention
Fig. 1 is the high-efficient liquid phase chromatogram of 1 gained aminomethylbenzoic acid of embodiment.
Fig. 2 is the high-efficient liquid phase chromatogram of 2 gained aminomethylbenzoic acid of embodiment.
Fig. 3 is the high-efficient liquid phase chromatogram of 3 gained aminomethylbenzoic acid of embodiment.
Specific embodiment
The technical scheme in the embodiments of the invention will be clearly and completely described below, it is clear that described implementation
Example is only a part of the embodiment of the present invention, rather than whole embodiments, based on the embodiments of the present invention, the common skill in this field
Art personnel every other embodiment obtained without making creative work belongs to the model that the present invention protects
It encloses, present invention will be further explained below with reference to the attached drawings and specific examples.
Embodiment 1
A kind of preparation method of aminomethylbenzoic acid of the embodiment of the present invention, including：
The 4- chloromethyl benzoic acid for weighing 40g is dissolved in the methanol of 1100g, obtains mixed solution；
The concentrated ammonia liquor (mass fraction 25%) of 70g is added into mixed solution, controlled at 60 DEG C, operating pressure is
0.3Mpa carries out reaction 4h in titanium reaction vessel, and 4- chloromethyl benzoic acid is made to be changed into Aminomethylbenzoic Acid, and vacuum is taken out
Aminomethylbenzoic acid is obtained after filter, Fig. 1 is the high-efficient liquid phase chromatogram (HPLC) of 1 gained aminomethylbenzoic acid of embodiment, as can be seen from Fig.,
The purity of aminomethylbenzoic acid reaches 99.51% in products therefrom, retention time 4.94min, sample analysis unit：Hunan Dongting Lake medicine
Industry limited liability company.
Chemical reaction process of the invention is：
Embodiment 2
A kind of preparation method of aminomethylbenzoic acid of the embodiment of the present invention, including：
The 4- chloromethyl benzoic acid for weighing 50g is dissolved in the methanol of 900g, obtains mixed solution；
The concentrated ammonia liquor (mass fraction 28%) of 80g is added into mixed solution, controlled at 80 DEG C, operating pressure is
0.5Mpa carries out reaction 1h in titanium reaction vessel, and 4- chloromethyl benzoic acid is made to be changed into Aminomethylbenzoic Acid, and vacuum is taken out
Aminomethylbenzoic acid is obtained after filter, Fig. 2 is the high-efficient liquid phase chromatogram (HPLC) of 2 gained aminomethylbenzoic acid of embodiment, as can be seen from Fig.,
The purity of aminomethylbenzoic acid reaches 99.55% in products therefrom, retention time 4.93min, sample analysis unit：Hunan Dongting Lake medicine
Industry limited liability company.
Embodiment 3
A kind of preparation method of aminomethylbenzoic acid of the embodiment of the present invention, including：
The 4- chloromethyl benzoic acid for weighing 35g is dissolved in the methanol of 1300g, obtains mixed solution；
The concentrated ammonia liquor (mass fraction 26%) of 60g is added into mixed solution, controlled at 40 DEG C, operating pressure is
0.2Mpa carries out reaction 5h in enamel reaction vessel, and 4- chloromethyl benzoic acid is made to be changed into Aminomethylbenzoic Acid, vacuum
Aminomethylbenzoic acid is obtained after suction filtration, Fig. 3 is the high-efficient liquid phase chromatogram (HPLC) of 3 gained aminomethylbenzoic acid of embodiment, can from figure
Out, the purity of aminomethylbenzoic acid reaches 99.55% in products therefrom, retention time 4.95min, sample analysis unit：Hu Nandong
Front yard medicine company limited liability company.
The above is only a preferred embodiment of the present invention, protection scope of the present invention is not limited merely to above-mentioned implementation
Example.To those of ordinary skill in the art, obtained improvement and change in the case where not departing from the technology of the present invention concept thereof
It changes and also should be regarded as protection scope of the present invention.
Claims (8)
1. a kind of preparation method of aminomethylbenzoic acid, which is characterized in that including：
In methyl alcohol by the dissolution of 4- chloromethyl benzoic acid, mixed solution is obtained；
Concentrated ammonia liquor is added into mixed solution, control reaction temperature is 40~80 DEG C, is reacted in the reaction vessel, makes 4- chlorine
Methyl benzoic acid is changed into Aminomethylbenzoic Acid, and the aminomethylbenzoic acid is obtained after separation of solid and liquid.
2. the preparation method of aminomethylbenzoic acid according to claim 1, which is characterized in that the reaction temperature is 60~80 DEG C.
3. the preparation method of aminomethylbenzoic acid according to claim 1, which is characterized in that the mass percent of the ammonium hydroxide is
25%~28%.
4. the preparation method of aminomethylbenzoic acid according to claim 1 or claim 2, which is characterized in that the ammonia and 4- chloromethylbenzene first
The molar ratio of acid is (4~5):1.
5. the preparation method of aminomethylbenzoic acid according to claim 1, which is characterized in that the mass ratio of the methanol and reactant
For (10~30):1, the reactant is 4- chloromethyl benzoic acid and ammonia.
6. the preparation method of aminomethylbenzoic acid according to claim 1, which is characterized in that the reaction time is 1~5h.
7. the preparation method of aminomethylbenzoic acid according to claim 1, which is characterized in that the operating pressure of the reaction vessel is
0.1~0.5Mpa.
8. according to claim 1 or the preparation method of 7 aminomethylbenzoic acids, which is characterized in that the material of the reaction vessel is
Enamel or titanium.
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| CN201810677509.8A CN108912002A (en) | 2018-06-27 | 2018-06-27 | The preparation method of aminomethylbenzoic acid |
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| CN201810677509.8A CN108912002A (en) | 2018-06-27 | 2018-06-27 | The preparation method of aminomethylbenzoic acid |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114014768A (en) * | 2021-12-03 | 2022-02-08 | 南京科瑞健医药科技有限公司 | Tranexamic acid without barium salt impurity and preparation method and preparation composition thereof |
| CN114057592A (en) * | 2020-08-05 | 2022-02-18 | 沈阳化工研究院有限公司 | Method for preparing 4-aminomethylbenzoic acid |
| CN114478281A (en) * | 2022-01-25 | 2022-05-13 | 上海巽田科技股份有限公司 | Preparation method of aminomethylbenzoic acid |
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| WO2009143101A2 (en) * | 2008-05-19 | 2009-11-26 | Bracco Imaging S.P.A. | Gastrin releasing peptide compounds |
| CN102718673A (en) * | 2011-12-16 | 2012-10-10 | 常江 | Novel technology for synthesis of aminomethylbenzoic acid |
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2018
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2009143101A2 (en) * | 2008-05-19 | 2009-11-26 | Bracco Imaging S.P.A. | Gastrin releasing peptide compounds |
| CN102718673A (en) * | 2011-12-16 | 2012-10-10 | 常江 | Novel technology for synthesis of aminomethylbenzoic acid |
Non-Patent Citations (1)
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114057592A (en) * | 2020-08-05 | 2022-02-18 | 沈阳化工研究院有限公司 | Method for preparing 4-aminomethylbenzoic acid |
| CN114057592B (en) * | 2020-08-05 | 2023-08-22 | 沈阳化工研究院有限公司 | Method for preparing 4-aminomethylbenzoic acid |
| CN114014768A (en) * | 2021-12-03 | 2022-02-08 | 南京科瑞健医药科技有限公司 | Tranexamic acid without barium salt impurity and preparation method and preparation composition thereof |
| CN114478281A (en) * | 2022-01-25 | 2022-05-13 | 上海巽田科技股份有限公司 | Preparation method of aminomethylbenzoic acid |
| CN114478281B (en) * | 2022-01-25 | 2024-01-26 | 上海巽田科技股份有限公司 | Preparation method of aminomethylbenzoic acid |
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Application publication date: 20181130 |