CN103755598A - Synthesis method of agmatine sulfate - Google Patents
Synthesis method of agmatine sulfate Download PDFInfo
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- CN103755598A CN103755598A CN201410032661.2A CN201410032661A CN103755598A CN 103755598 A CN103755598 A CN 103755598A CN 201410032661 A CN201410032661 A CN 201410032661A CN 103755598 A CN103755598 A CN 103755598A
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- agmatine
- cyanamide
- synthetic method
- agmatine sulfate
- reaction
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Abstract
The invention provides a synthesis method of agmatine sulfate. The method comprises the steps of carrying out addition reaction by taking 1,4-butanediamine as a raw material and a cyanamide water solution as a guanidination reagent to obtain agmatine, and forming salt with sulfuric acid to obtain agmatine sulfate. The synthesis method disclosed by the invention, by taking cyanamide water solution as the guanidination reagent, is moderate in reaction condition, easy to control, light in pollution, favorable for environmental protection, low in cost, and suitable for industrial production and application on a large scale.
Description
Technical field
The present invention relates to a kind of synthetic method of arginine derivative, particularly, relate to a kind of synthetic method of agmatine sulfate.
Background technology
Agmatine is the decarboxylized product of L-arginine decarboxylase (L-ADC) catalysis arginine, is a kind of neurotransmitter, in the most organs in mammalian body and tissue, all has distribution, and its content is organ specificity.Research data shows, the biological activitys such as that agmatine has is hypoglycemic, hypotensive, diuresis, anti-inflammatory, antidepressant, inhibition of cell proliferation, particularly to the antagonistic action of N-methyl-D-aspartate acceptor compared with strong and lasting, there is the Withdrawal Effect according to lazyness to animal morphine, it is a kind of drug rehabilitation class medicine that exploitation is worth that has, as the pharmaceutical salts of agmatine, the market of agmatine sulfate uses and has a extensive future.
At present, the synthetic method of agmatine sulfate mainly contains following two kinds:
(1), take Putriscine as raw material, S-methyl-isourea is guanidinated reagent, shown in following reaction formula, the advantage of the method is that cost is low, shortcoming is to produce poisonous thiomethyl alcohol gas, and environment is caused to larger pollution.
(2), take Putriscine as raw material, O-methyl-isourea is guanidinated reagent, shown in following reaction formula, the advantage of the method is that shortcoming is that yield is low with respect to method (1) environmental protection, raw materials cost is high, causes production cost high.
Summary of the invention
The synthetic method that the object of the invention is to overcome the defect of above-mentioned prior art existence and provide a kind of agmatine sulfate, the present invention has advantages of that pollution is little, cost is low, is applicable to suitability for industrialized production application.
Object of the present invention is achieved through the following technical solutions, and a kind of synthetic method of agmatine sulfate, comprises the following steps: with 1,4-butanediamine is raw material, using the cyanamide aqueous solution as guanidinated reagent, by addition reaction, obtains agmatine, use again sulfuric acid salify, obtain.
Preferably, the ratio of the mole number of described Putriscine and described cyanamide is 1:(1～2).
Preferably, in the described cyanamide aqueous solution, the percent weight in volume content of cyanamide is 25～50%.
Preferably, the temperature of reaction of described addition reaction is 50～90 ℃.
Preferably, the reaction times of described addition reaction is 10～30h.
Shown in the following reaction formula of reaction principle of the present invention:
Compared with prior art, the present invention has following beneficial effect: the present invention adopts the cyanamide aqueous solution as guanidinated reagent, and reaction conditions gentleness is easy to control; Pollute littlely, be conducive to environment protection; Cost is low, is applicable to large-scale industrialization production application.
Embodiment
Below in conjunction with specific embodiment, the present invention is described in detail.Following examples will contribute to those skilled in the art further to understand the present invention, but not limit in any form the present invention.It should be pointed out that to those skilled in the art, without departing from the inventive concept of the premise, can also make some distortion and improvement.These all belong to protection scope of the present invention.
embodiment 1, a kind of agmatine sulfate synthetic method
A kind of synthetic method of agmatine sulfate, comprise the following steps: take the Putriscine of 88g (1mol) as raw material, take the cyanamide aqueous solution of 168mL, (the percent weight in volume content of cyanamide is as 25%, containing cyanamide 1mol) as guanidinated reagent, carry out addition reaction, temperature of reaction is 50 ℃, and the reaction times is 30h, can obtain agmatine, use sulfuric acid salify again, obtain, purity is 99.8%.
The detection data of products therefrom are as follows: m.p.:234.1～236.8 ℃.
1H-NMR(D
2O;500MHz):1.60（m,4H），2.90(t,J=6.0Hz,2H)，3.11(t,J=5.2Hz,2H)。IR(KBr):3373，3164，1665，1131cm
-1。MS(CI)m/z:228(M
+)。Ultimate analysis C
5h
14n
4h
2sO
4: theoretical value C:26.3%, H:7.0%, N:24.6%; Experimental value C:26.3%, H:7.0%, N:24.6%.
embodiment 2, a kind of agmatine sulfate synthetic method
A kind of synthetic method of agmatine sulfate, comprise the following steps: take the Putriscine of 88g (1mol) as raw material, take the 140mL cyanamide aqueous solution, (the percent weight in volume content of cyanamide is as 45%, containing cyanamide 1.5mol) as guanidinated reagent, carry out addition reaction, temperature of reaction is 70 ℃, and the reaction times is 20h, can obtain agmatine, use sulfuric acid salify again, obtain, purity is 99.6%.
The detection data of products therefrom are as follows: m.p.:235.0～236.5 ℃.
1H-NMR(D
2O;500MHz):1.60（m,4H），2.90(t,J=6.0Hz,2H)，3.11(t,J=5.2Hz,2H)。IR(KBr):3373，3164，1665，1131cm
-1。MS(CI)m/z:228(M
+)。Ultimate analysis C
5h
14n
4h
2sO
4: theoretical value C:26.3%, H:7.0%, N:24.6%; Experimental value C:26.3%, H:7.0%, N:24.6%.
embodiment 3, a kind of agmatine sulfate synthetic method
A synthetic method for agmatine sulfate, comprises the following steps: take the Putriscine of 88g (1mol) as raw material, take the 168mL cyanamide aqueous solution, (the percent weight in volume content of cyanamide is as 50%, containing cyanamide 2mol) as guanidinated reagent, carry out addition reaction, temperature of reaction is 90 ℃, reaction times is 10h, can obtain agmatine, then use sulfuric acid salify, obtain, obtain, purity is 99.7%.
The detection data of products therefrom are as follows: m.p.:234.5～236.6 ℃.
1H-NMR(D
2O;500MHz):1.60（m,4H），2.90(t,J=6.0Hz,2H)，3.11(t,J=5.2Hz,2H)。IR(KBr):3373，3164，1665，1131cm
-1。MS(m/z):228(M
+)。Ultimate analysis C
5h
14n
4h
2sO
4: theoretical value C:26.3%, H:7.0%, N:24.6%; Experimental value C:26.3%, H:7.0%, N:24.6%.
Above specific embodiments of the invention are described.It will be appreciated that, the present invention is not limited to above-mentioned specific implementations, and those skilled in the art can make various distortion or modification within the scope of the claims, and this does not affect flesh and blood of the present invention.
Claims (5)
1. a synthetic method for agmatine sulfate, is characterized in that, comprises the following steps: take Putriscine as raw material, using the cyanamide aqueous solution as guanidinated reagent, by addition reaction, obtain agmatine, then use sulfuric acid salify, obtain.
2. the synthetic method of agmatine sulfate as claimed in claim 1, is characterized in that, the ratio of the mole number of described Putriscine and described cyanamide is 1:(1～2).
3. the synthetic method of agmatine sulfate as claimed in claim 1, is characterized in that, in the described cyanamide aqueous solution, the percent weight in volume content of cyanamide is 25～50%.
4. the synthetic method of agmatine sulfate as claimed in claim 1, is characterized in that, the temperature of reaction of described addition reaction is 50～90 ℃.
5. the synthetic method of agmatine sulfate as claimed in claim 1, is characterized in that, the reaction times of described addition reaction is 10～30h.
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| CN201410032661.2A CN103755598A (en) | 2014-01-23 | 2014-01-23 | Synthesis method of agmatine sulfate |
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| CN201410032661.2A CN103755598A (en) | 2014-01-23 | 2014-01-23 | Synthesis method of agmatine sulfate |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106631909A (en) * | 2016-09-22 | 2017-05-10 | 精晶药业股份有限公司 | Agmatine hydrochloride preparation method |
Citations (5)
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|---|---|---|---|---|
| CN101062906A (en) * | 2006-04-26 | 2007-10-31 | 中国人民解放军军事医学科学院毒物药物研究所 | Agmatine sulfate hydrate and usage for drug rehabilitation, antiphlogistic, hypoglycemic and agmatine metabolism abnormality induced disease |
| CN101121677A (en) * | 2006-08-09 | 2008-02-13 | 中国人民解放军军事医学科学院毒物药物研究所 | Agmatine sulfate dihydrate and medical use thereof |
| CN101717352A (en) * | 2009-11-30 | 2010-06-02 | 浙江工业大学 | Method for synthesizing agmatine sulfate |
| JP2010155963A (en) * | 2008-12-01 | 2010-07-15 | Kao Corp | Biofilm removing agent composition |
| CN102665406A (en) * | 2009-12-24 | 2012-09-12 | 诺沃梅尔公司 | Methods for the synthesis of polycyclic guanidine compounds |
-
2014
- 2014-01-23 CN CN201410032661.2A patent/CN103755598A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101062906A (en) * | 2006-04-26 | 2007-10-31 | 中国人民解放军军事医学科学院毒物药物研究所 | Agmatine sulfate hydrate and usage for drug rehabilitation, antiphlogistic, hypoglycemic and agmatine metabolism abnormality induced disease |
| CN101121677A (en) * | 2006-08-09 | 2008-02-13 | 中国人民解放军军事医学科学院毒物药物研究所 | Agmatine sulfate dihydrate and medical use thereof |
| JP2010155963A (en) * | 2008-12-01 | 2010-07-15 | Kao Corp | Biofilm removing agent composition |
| CN101717352A (en) * | 2009-11-30 | 2010-06-02 | 浙江工业大学 | Method for synthesizing agmatine sulfate |
| CN102665406A (en) * | 2009-12-24 | 2012-09-12 | 诺沃梅尔公司 | Methods for the synthesis of polycyclic guanidine compounds |
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| 赵声贵等: "胍基化合物的制备方法及其应用", 《精细化工中间体》 * |
| 黄春华等: "醋酸十八胍的合成", 《化工时刊》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106631909A (en) * | 2016-09-22 | 2017-05-10 | 精晶药业股份有限公司 | Agmatine hydrochloride preparation method |
| CN106631909B (en) * | 2016-09-22 | 2018-11-09 | 精晶药业股份有限公司 | A kind of preparation method of gamatine hydrochloride |
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Application publication date: 20140430 |