CN113999146A - Synthesis method of 4-guanidinobutyric acid - Google Patents
Synthesis method of 4-guanidinobutyric acid Download PDFInfo
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- CN113999146A CN113999146A CN202111503053.1A CN202111503053A CN113999146A CN 113999146 A CN113999146 A CN 113999146A CN 202111503053 A CN202111503053 A CN 202111503053A CN 113999146 A CN113999146 A CN 113999146A
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- guanidinobutyric acid
- arginine
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C277/00—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C277/08—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups of substituted guanidines
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Abstract
The invention discloses a synthesis method of 4-guanidinobutyric acid, belonging to the field of preparation of guanidine derivatives. Taking L-arginine and hydrogen peroxide solution as raw materials, and carrying out oxidation-reduction reaction in aqueous solution to generate 4-guanidino butyric acid. The raw materials are cheap and easy to obtain, the preparation method is simple, the yield is high, the side reaction is less, the purification is easy, and the method is suitable for large-scale industrial application.
Description
Technical Field
The invention belongs to the technical field of preparation of guanidine derivatives, and particularly relates to a synthesis method of 4-guanidinobutyric acid.
Background
4-guanidinobutyric acid is an alkaloid in guanidino compounds, and is present in the brain of mammals, various plants, fishes and shellfishes. 4-guanidinobutyric acid is produced in humans by the oxidation of arginine by amino acid oxidase enzymes, is involved in a variety of important physiological activities, and is a biomarker for many diseases.
In addition to being responsible for important physiological functions, 4-guanidinobutyric acid may also be used as a functional additive in many fields. 4-guanidinobutyric acid has both strong electropositive guanidinobutyric group and electronegative carboxyl group, and can regulate the charge distribution, water affinity and other properties of the material, so that the material has wide application in the field of functional materials. 4-guanidinobutyric acid is also one of the starting materials in the organic synthesis step of guanidine compounds. Therefore, there is an important practical need to develop a simple synthetic method of 4-guanidinobutyric acid and its analogs.
The current synthesis method of 4-guanidinobutyric acid usually involves many complex raw material molecules and many byproducts exist in the product, which is not suitable for large-scale industrial application. The preparation method of the 4-guanidinobutyric acid is greatly simplified, and byproducts which are difficult to separate are avoided, so that the preparation method is expected to provide more practical technical support for the preparation of the 4-guanidinobutyric acid and similar derivatives.
Disclosure of Invention
The invention aims to provide a method for synthesizing 4-guanidino butyric acid, which adopts L-arginine and hydrogen peroxide to react in aqueous solution at room temperature to synthesize the 4-guanidino butyric acid. The raw materials are cheap and easy to obtain, the preparation method is simple, the yield is high, the side reaction is less, the purification is easy, and the method is suitable for large-scale industrial application.
In order to achieve the purpose, the invention adopts the following technical scheme:
a method for synthesizing 4-guanidinobutyric acid comprises the following steps:
(1) synthesis of 4-guanidinobutyric acid:
a. dissolving L-arginine in redistilled water;
b. adding a hydrogen peroxide solution to the L-arginine solution;
c. and after standing reaction at room temperature, concentrating and cooling the mixed solution to 0-5 ℃, and filtering to obtain a solid, namely a crude product of the 4-guanidinobutyric acid.
(2) Purification of 4-guanidinobutyric acid:
d. adding the crude product of the 4-guanidinobutyric acid into a small amount of secondary distilled water, and heating and dissolving at the temperature of below 80 ℃;
e. slowly cooling the crude product solution to 0-5 ℃ to separate out crystals;
f. and filtering the crystal product and drying at 50-60 ℃ to obtain the 4-guanidinobutyric acid product.
L-arginine used in the step (1) aThe mass ratio of acid to water is 10-4:1~10-1:1。
The molar ratio of the hydrogen peroxide to the L-arginine used in the step (1) b is 10: 1-100: 1.
The reaction time in the step (1) c is 24-72 hours.
The mass ratio of the 4-guanidinobutyric acid crude product used in the step (1) d to water is 1: 2-1: 5.
The invention has the beneficial effects that:
the invention provides a novel preparation method of 4-guanidinobutyric acid, which is simple to operate, has easily obtained raw materials and can be used as a large-scale industrial synthesis method of the 4-guanidinobutyric acid and similar derivatives.
Drawings
FIG. 1 shows the mass spectrometric detection of 4-guanidinobutyric acid synthesized in example 1.
FIG. 2 is a nuclear magnetic resonance hydrogen spectrum of 4-guanidinobutyric acid synthesized in example 1.
Detailed Description
A method for synthesizing 4-guanidinobutyric acid comprises the following steps:
(1) synthesis of 4-guanidinobutyric acid:
a. dissolving L-arginine in secondary distilled water at a mass ratio of L-arginine to water of 10-4:1~10-1:1；
b. Adding a hydrogen peroxide solution into the L-arginine solution, wherein the molar ratio of the hydrogen peroxide to the L-arginine is 10: 1-100: 1;
c. and (3) after standing reaction for 24-72 hours at room temperature, concentrating and cooling the mixed solution to 0-5 ℃, and filtering to obtain a solid, namely a crude product of the 4-guanidinobutyric acid.
(2) Purification of 4-guanidinobutyric acid:
d. adding the crude product of the 4-guanidinobutyric acid into a small amount of secondary distilled water, wherein the mass ratio of the crude product of the 4-guanidinobutyric acid to the water is 1: 2-1: 5, and heating and dissolving the crude product of the 4-guanidinobutyric acid at the temperature of below 80 ℃;
e. slowly cooling the crude product solution to 0-5 ℃ to separate out crystals;
f. and filtering the crystal product and drying at 50-60 ℃ to obtain the 4-guanidinobutyric acid product.
In order to make the present invention more comprehensible, the technical solutions of the present invention are further described below with reference to specific embodiments, but the present invention is not limited thereto.
Example 1
A method for synthesizing 4-guanidinobutyric acid comprises the following steps:
(1) synthesis of 4-guanidinobutyric acid:
a. adding 17.42 g (0.1 mol) of L-arginine and 1L of secondary distilled water into a reaction vessel, and stirring to dissolve;
b. adding 400 mL of 30% hydrogen peroxide solution into the L-arginine solution, wherein the total mole number of hydrogen peroxide is 4 mol;
c. after allowing the reaction mixture to stand at room temperature for 72 hours, the mixture was transferred to a round-bottomed flask and concentrated to 50 mL of an aqueous solution by rotary evaporation at 50 ℃ and 30 mbar. And then cooling the concentrated solution to 4 ℃, and filtering to obtain a solid, namely a crude product of the 4-guanidinobutyric acid.
(2) Purification of 4-guanidinobutyric acid:
d. adding 10 g of the crude product of the 4-guanidinobutyric acid into 30 mL of secondary distilled water, and heating to 80 ℃ to completely dissolve the crude product;
e. slowly cooling the crude product solution to 0 ℃ to separate out crystals;
f. and filtering the crystal product and drying at 60 ℃ to obtain the 4-guanidinobutyric acid product.
Mass spectrometric detection (FIG. 1) and NMR spectra (FIG. 2) of the 4-guanidinobutyric acid synthesized in example 1. The mass spectrum detection result and the nuclear magnetic resonance hydrogen spectrum of the 4-guanidinobutyric acid are consistent with those of the standard product, which shows that the purity of the 4-guanidinobutyric acid synthesized by the method is higher and the byproducts are less.
The above description is only a preferred embodiment of the present invention, and all equivalent changes and modifications, such as an increase or decrease in the number of carbon atoms of L-arginine in the reaction material to produce similar compounds with different numbers of carbon atoms, made according to the claims of the present invention should be covered by the present invention.
Claims (6)
1. A method for synthesizing 4-guanidinobutyric acid is characterized by comprising the following steps: the method comprises the following steps:
(1) synthesis of 4-guanidinobutyric acid:
a. dissolving L-arginine in redistilled water;
b. adding a hydrogen peroxide solution to the L-arginine solution;
c. after standing reaction at room temperature, concentrating and cooling the mixed solution to 0-5 ℃, and filtering to obtain a solid, namely a crude product of 4-guanidinobutyric acid;
(2) purification of 4-guanidinobutyric acid:
d. adding the crude product of the 4-guanidinobutyric acid into secondary distilled water, and heating and dissolving at the temperature of below 80 ℃;
e. slowly cooling the crude product solution to 0-5 ℃ to separate out crystals;
f. and filtering and drying the crystal product to obtain the 4-guanidinobutyric acid product.
2. The method of claim 1, wherein: the mass ratio of the L-arginine to the water in the step (1) a is 10-4:1~10-1:1。
3. The method of claim 1, wherein: the molar ratio of the hydrogen peroxide to the L-arginine in the step (1) b is 10: 1-100: 1.
4. The method of claim 1, wherein: the reaction time in the step (1) c is 24-72 hours.
5. The method of claim 1, wherein: in the step (1), the mass ratio of the crude product of the 4-guanidinobutyric acid to the water is 1: 2-1: 5.
6. The method of claim 1, wherein: and f, drying at 50-60 ℃.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080213845A1 (en) * | 2007-03-02 | 2008-09-04 | Richmond Chemical Corporation | Method to increase the yield and improve purification of products from transaminase reactions |
| CN110669798A (en) * | 2019-10-31 | 2020-01-10 | 内蒙古阜丰生物科技有限公司 | Production method of agricultural low-cost polyglutamic acid |
| JP2021136916A (en) * | 2020-03-04 | 2021-09-16 | 学校法人甲南学園 | Device and method for producing the same |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080213845A1 (en) * | 2007-03-02 | 2008-09-04 | Richmond Chemical Corporation | Method to increase the yield and improve purification of products from transaminase reactions |
| CN110669798A (en) * | 2019-10-31 | 2020-01-10 | 内蒙古阜丰生物科技有限公司 | Production method of agricultural low-cost polyglutamic acid |
| JP2021136916A (en) * | 2020-03-04 | 2021-09-16 | 学校法人甲南学園 | Device and method for producing the same |
Non-Patent Citations (6)
| Title |
|---|
| ADAM WALDEMAR ET AL: "Dioxirane oxidations of compounds other than alkenes", 《ORGANIC REACTIONS》 * |
| DU YILING ET AL: "A pyridoxal phosphate-dependent enzyme that oxidizes an unactivated carbon-carbon bond", 《NATURE CHEMICAL BIOLOGY》 * |
| HONG HU ET AL: "ACommon Origin for Guanidinobutanoate Starter Units in Antifungal Natural Products" * |
| MATSUI DAISUKE ET AL: "L-Arginine oxidase from Pseudomonas sp. TPU 7192: Characterization, gene cloning, heterologous expression, and application to L-arginine determination", 《ENZYME AND MICROBIAL TECHNOLOGY》 * |
| PARADKAR VIDYADHAR M.ET AL: "Oxidative decarboxylation of α-amino acids with in situ generated dimethyl dioxirane", 《SYNLETT》 * |
| 陈文如等: "4-胍基丁酸的合成", 《山东化工》 * |
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