CN107382790A - The phosphatic synthetic method of creatinol - Google Patents
The phosphatic synthetic method of creatinol Download PDFInfo
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- CN107382790A CN107382790A CN201710619032.3A CN201710619032A CN107382790A CN 107382790 A CN107382790 A CN 107382790A CN 201710619032 A CN201710619032 A CN 201710619032A CN 107382790 A CN107382790 A CN 107382790A
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- C—CHEMISTRY; METALLURGY
- 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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- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01C—AMMONIA; CYANOGEN; COMPOUNDS THEREOF
- C01C3/00—Cyanogen; Compounds thereof
- C01C3/16—Cyanamide; Salts thereof
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a kind of phosphatic synthetic method of creatinol, including step are as follows：(1) lime nitrogen is added in ethanol and water mixed solution under carbon dioxide atmosphere, is continually fed into carbon dioxide and causes reaction solution pH to 7.5~8.5, filter cyanamide ethanol solution；(2) concentrated phosphoric acid regulation pH to 5~7 is added into ethanol and 2 (methylamino) ethanol solutions, the ethanol solution of the cyanamide in step (1) is added dropwise thereto under 50~70 DEG C of temperature conditionss, white creatinol calcium phosphate precipitation is reacted to obtain, purifies to obtain creatinol phosphate.The present invention is reacted directly using ethanol as solvent using the ethanol solution containing a small amount of water and lime nitrogen, and it is difficult to effectively prevent product crystallizing and separating caused by water is present.This method cost of material is low, and technique is simple, is easy to industrialized production, product purity and high income, and the discharge capacity of waste water is few, meets green production theory.
Description
Technical field
The invention belongs to organic synthesis field, and in particular to a kind of phosphatic synthetic method of creatinol.
Background technology
Creatinol phosphate, it is the important as precursors for synthesizing creatinol-o-phosphate.Creatinol phosphate converts ADP in human body
For ATP, the ATP rapid regenerations during strenuous activity are made one, to retain the energy of muscle.Therefore it is a kind of efficient motion work(
Can food additives, can play and quickly supplement energy, alleviate muscular movement fatigue the effect of.Contain hydroxyl in creatinol structure
Base, for the creatine containing carboxyl that compares, it is not easy to cyclization occurs and generates creatinine, so creatinol can carry out phosphorus
Acylation reaction generates the energy matter as creatine.And creatinol phosphate is highly soluble in water, feature can be used as to drink
The additive of material, directly drunk by human body.With the fast development of China's motion industry, the demand of relative motion functional food
To quickly it increase, the phosphatic wide market of creatinol.Creatinol phosphate is also many important medicine and chemical industry simultaneously
The basic material of product, important basic raw material is especially belonged in new guanidine drug development, utilizes creatinol phosphate
For the creatinol-o-phosphate of Material synthesis, it can be used for treating heart disease, there is special efficacy for symptoms such as myocardial kinetic deficiencies.
Therefore a kind of synthesis technique is simple, safe, high yield, high-purity, and low cost is pollution-free, and " green " chemistry of energy-saving and emission-reduction closes
Into process route, there will be great meaning to industries such as medicine and chemical industry.
Creatinol phosphate structure formula is as follows：
The phosphatic synthetic method of creatinol mainly has following several at present：
(1) reacted with S- Ethyl isothiuroniums hydrobromate and 2- (methylamino) ethanol in the case of a small amount of water as solvent,
Generate creatinol hydrobromate.Creatinol hydrobromate is added portionwise into the ethanol solution containing NaOH, separates out bromination
Sodium precipitates, and is filtrated to get creatinol alkali, adds orthophosphoric acid and obtain creatinol phosphate (Siphar, S.A., et al.Patent
1987,CH516596A).Its reaction equation is as follows：
But such a process route cost is higher, and the easy moisture absorption of intermediate products creatinol hydrobromic acid hydrochlorate, it is not easy to store.
Ethyl mercaptan can be produced during simultaneously synthesizing, air pollution is serious.
(2) methanol as solvent is used, makees raw material with the cyanamide aqueous solution and N- methyl amino ethanols, with strong sulfuric acid response, subtracts
After pressure concentration, add organic solvent and separate out creatinol sulphate crystallization.With creatinol sulphate and NaOH solution neutralize instead
Should, creatinol alkali is isolated, then creatinol alkali and organic acid are reacted to the corresponding muscle alkoxide of generation in methanol solution
(Zhang,G.J.et al.Patent 2011,US20110105797；Zhang Guoji .Patent 2009CN101671282).Its
Reaction equation is as follows：
But the method, with cyanamide Syntheses in water, the presence of whole technical process reclaimed water is during phosphate is formed
Because mutual strong hydrogen bonding acts on, sticky mass is readily obtained, crystallization filter process is difficult, and overall yield is relatively low.
(3) first by the use of thiocarbamide and dimethyl suflfate as initiation material, reaction generation S- methyl-isoureas, then by its
Creatinol sulphate is generated with 2- (methylamino) ethanol synthesis, creatinol sulphate and NaOH solution are neutralized, isolated free
Creatinol alkali, finally add organic acid, corresponding muscle alkoxide obtained into salt combined method with soda acid.The program can be used for
Produce creatinol formates, creatinol acetate, creatinol butyrate, creatinol phosphate, creatinol laruate, creatinol
More than the 40 kinds of muscle alkoxide such as substituted benzoic acid salt, creatinol substituted pyridines hydrochlorate (Henri, C.et al.Patent 1974,
GB1468998；Farber, S.P.et al.Patent 1971, FR7143973；Sun Xiaohong etc., creatinol substituted pyridines hydrochlorate
Synthesis and bioactivity [J], Chemical Engineering, 2011,39 (1), 77-80,102), its reaction equation is as follows：
The method can produce unpleasant mercaptan material in building-up process, while the moisture that alkali tune, desalinization of soil by flooding or leaching process are brought into makes
Obtain final phosphate and form rear crystallization filtration difficulty.
(4) organic acid is added dropwise in the mixture of isopropanol and 2- (methylamino) ethanol, cyanamide is then added portionwise again
Solid, after being heated to reflux 1.5h, cold filtration, washed with a small amount of isopropanol, you can obtain corresponding muscle alkoxide.The party
Case can be used for production creatinol formates, creatinol acetate, creatinol succinate, creatinol propionate, creatinol nitric acid
The product such as salt, creatinol benzoate (Guerrato, A.et al.Patent 1986, IT2218886.Its reaction equation is such as
Under：
Although this technical scheme effectively avoids bringing into for moisture in synthesis process, raw material solid cyanamide mesh
Preceding not yet commercialization, storage, transport difficult, cost are high.
In addition thank it is refined et al. (Xie Bin etc., the phosphatic study on the synthesis of creatinol, Northwest University's journal (natural science edition),
2010,40 (5), 818-820) report using N- methylaminoethanols and cyanamide as raw material, it is anti-with glacial acetic acid using ethanol as solvent
Creatinol acetate should be generated, creatinol phosphate is then obtained with phosphatase reaction.Yield is up to 71%.But this process is same
Crystallizing and separating difficulty be present, acetic acid volatilization taste is big, adds the harmful substance in synthesis cost and waste water, while adds and pair set
Standby corrosivity.
The content of the invention
For above-mentioned the deficiencies in the prior art, inventor passes through long-term technology and practical exploration, there is provided a kind of new flesh
The phosphatic synthetic method of meat alcohol, this method cost of material is low, and technique is simple, is easy to industrialized production, product purity and yield
Height, the discharge capacity of waste water is few, meets green production theory.
Specifically, the present invention relates to following technical scheme：
The first aspect of the invention, discloses a kind of phosphatic synthetic method of creatinol, including step is as follows：
(1) lime nitrogen is added in ethanol and water mixed solution under carbon dioxide atmosphere, being continually fed into carbon dioxide makes
Reaction solution pH to 7.5~8.5, filter cyanamide ethanol solution；
(2) concentrated phosphoric acid regulation pH to 5~7 is added into ethanol and 2- (methylamino) ethanol solution, in 50~70 DEG C of temperature
Under the conditions of the ethanol solution of cyanamide in step (1) is added dropwise thereto, react to obtain white creatinol calcium phosphate precipitation, purify
Creatinol phosphate.
Preferably, in step (1) ethanol, lime nitrogen and water mass ratio (10~20)：(3~5)：(1~2), it is preferably
15：4：1；The reaction solution pH is 8；
Preferably, the mass fraction of the ethanol is 95%, the nitrogen content of lime nitrogen>20%；
Preferably, to prevent accessory substance from generating, rate-determining steps (1) reaction temperature≤50 DEG C, still more preferably, use
Circulator bath mode controlling reaction temperature≤50 DEG C；
Preferably, the mass fraction of the concentrated phosphoric acid is 85%；
Preferably, the mass ratio of ethanol, 2- (methylamino) ethanol and phosphoric acid is (18~20) in the step (2)：(4~
6)：(7~9), preferably 20：5：8；
Still more preferably, the mass ratio of the lime nitrogen in step (1) and 2- (methylamino) ethanol in step (2) is
(5-6)：2, preferably 5:2；
Preferably, regulation pH to 6 in the step (2), controlling reaction temperature are 60 DEG C；
A kind of phosphatic synthetic method of creatinol, including step are as follows：
(1) in the reactor with mechanical agitator, 95% second alcohol and water is added, carbon dioxide is then passed to, is stirring
Mix lime nitrogen (nitrogen content under state>20%) it is added in reaction solution, lime nitrogen continues to be passed through carbon dioxide after adding
To pH=8, stop reaction, filtering obtains the ethanol solution of cyanamide, in whole course of reaction, is controlled by circulator bath anti-
Temperature is answered below 50 DEG C；
(2) 95% ethanol and 2- (methylamino) ethanol are added in the reactor with mechanical agitator, adds 85% phosphorus
Acid for adjusting pH is 6, and the ethanol solution of the cyanamide in step (1) is added dropwise in reaction system under the conditions of 60 DEG C, directly anti-
White creatinol calcium phosphate precipitation should be obtained, is filtered, absolute ethyl alcohol washing, vacuum drying, obtains creatinol phosphate；
Wherein, the mass ratio of 95% ethanol, lime nitrogen and water is 15 in step (1)：4：1；
The mass ratio of 95% ethanol, 2- (methylamino) ethanol and phosphoric acid is 20 in step (2)：5：8；
The mass ratio of lime nitrogen and 2- (methylamino) ethanol in step (2) is 5 in step (1):2.
The second aspect of the invention, disclose the creatinol phosphate that above-mentioned synthetic method prepares synthesis.
The third aspect of the invention, disclose above-mentioned synthetic method and preparing the application in synthesizing creatinol phosphate.
Beneficial effects of the present invention：
1st, the present invention is reacted using the ethanol solution containing a small amount of water and lime nitrogen, directly obtained directly using ethanol as solvent
Obtain the very low cyanamide ethanol solution of water content and obtain creatinol phosphate with 2- (methylamino) ethanol synthesis, effectively prevent water
Product crystallizing and separating is difficult in the presence of caused by；
2nd, the present invention is directly directly obtained in guanidinated workshop section by the use of phosphoric acid as the regulating acid agent of ethanol system, single step reaction
Creatinol phosphate insoluble in ethanol solution, avoids the generation of other salt impurity, effectively raises creatinol phosphate
Yield and purity are obtained, later product drying temperature is low, it is possible to prevente effectively from creatinol-o-phosphate esterification side reaction in drying process
Occur；
3rd, for the present invention with use ethanol as action solvent, later stage mother liquor is easy to purification to reclaim, primary first-order equation mother liquor and washing
Liquid can apply mechanically use with direct circulation, the basic non-wastewater discharge of integrated artistic, to equipment non-corrosiveness, green safe environmental protection, fit
Close industrialized production.
Brief description of the drawings
Fig. 1 is the hot ellipsoid figure of mono-crystalline structures of the synthetic product of the embodiment of the present invention 1；
Fig. 2 is the FTIR spectrograms of the synthetic product of the embodiment of the present invention 1；
Fig. 3 is the high-efficient liquid phase chromatogram of the synthetic product of case study on implementation 1 of the present invention.
Embodiment
It is noted that described further below is all exemplary, it is intended to provides further instruction to the application.It is unless another
Indicate, all technologies used herein and scientific terminology are with usual with the application person of an ordinary skill in the technical field
The identical meanings of understanding.
It should be noted that term used herein above is merely to describe embodiment, and be not intended to restricted root
According to the illustrative embodiments of the application.As used herein, unless the context clearly indicates otherwise, otherwise singulative
It is also intended to include plural form, additionally, it should be understood that, when in this manual using term "comprising" and/or " bag
Include " when, it indicates existing characteristics, step, operation, device, component and/or combinations thereof.
In the sense of the present invention, described purification process refers to the process of take out solid product from solvent, Ke Yiwei
Filtering, washing, the process dried, or the process for centrifuging, drying.
As background technology is introduced, there is provided a kind of synthesis technique is simple, safety, high yield, high-purity, low cost,
It is pollution-free, " green " chemical synthesis process route of energy-saving and emission-reduction, there is great meaning to industries such as medicine and chemical industry.
In view of this, in a kind of embodiment of the invention, there is provided a kind of phosphatic synthetic method of creatinol, bag
It is as follows to include step：
(1) lime nitrogen is added in ethanol and water mixed solution under carbon dioxide atmosphere, being continually fed into carbon dioxide makes
Reaction solution pH to 7.5~8.5, filter cyanamide ethanol solution；
(2) concentrated phosphoric acid regulation pH to 5~7 is added into ethanol and 2- (methylamino) ethanol solution, in 50~70 DEG C of temperature
Under the conditions of the ethanol solution of cyanamide in step (1) is added dropwise thereto, react to obtain white creatinol calcium phosphate precipitation, purify
Creatinol phosphate.
Wherein, in step (1) ethanol, lime nitrogen and water mass ratio (10~20)：(3~5)：(1~2), preferably 15：
4：1；The reaction solution pH is 8；Using aforementioned proportion, it both can guarantee that enough moisture participated in lime nitrogen hydrolysis, while also can
Avoid water content in final cyanamide solution too high；
The mass fraction of the ethanol is 95%, the nitrogen content of lime nitrogen>20%；
To prevent accessory substance from generating, rate-determining steps (1) reaction temperature≤50 DEG C, still more preferably, using recirculated water
Bath mode controlling reaction temperature≤50 DEG C；
The mass fraction of the concentrated phosphoric acid is 85%；
The mass ratio of ethanol, 2- (methylamino) ethanol and phosphoric acid is (18~20) in the step (2)：(4~6)：(7~
9), preferably 20：5：8；In this reactions steps, phosphoric acid also serves as precipitating reagent as regulating acid agent, directly obtains creatinol phosphorus
Hydrochlorate, the dehydration by evaporation of existing technique and the washing process of salt are avoided, significantly improve the purity and yield of product；
The mass ratio of lime nitrogen and 2- (methylamino) ethanol in step (2) in step (1) is (5-6)：2, be preferably
5:2；
Regulation pH to 6 in the step (2), controlling reaction temperature are 60 DEG C；
In the still another embodiment of the present invention, there is provided a kind of phosphatic synthetic method of creatinol, including step is such as
Under：
(1) in the reactor with mechanical agitator, 95% second alcohol and water is added, carbon dioxide is then passed to, is stirring
Mix lime nitrogen (nitrogen content under state>20%) it is added in reaction solution, lime nitrogen continues to be passed through carbon dioxide after adding
To pH=8, stop reaction, filtering obtains the ethanol solution of cyanamide, in whole course of reaction, is controlled by circulator bath anti-
Temperature is answered below 50 DEG C；
(2) 95% ethanol and 2- (methylamino) ethanol are added in the reactor with mechanical agitator, adds 85% phosphorus
Acid for adjusting pH is 6, and the ethanol solution of the cyanamide in step (1) is added dropwise in reaction system under the conditions of 60 DEG C, directly anti-
White creatinol calcium phosphate precipitation should be obtained, is filtered, absolute ethyl alcohol washing, vacuum drying, obtains creatinol phosphate；
Wherein, the mass ratio of 95% ethanol, lime nitrogen and water is 15 in step (1)：4：1；
The mass ratio of 95% ethanol, 2- (methylamino) ethanol and phosphoric acid is 20 in step (2)：5：8；
The mass ratio of lime nitrogen and 2- (methylamino) ethanol in step (2) is 5 in step (1):2.
In the still another embodiment of the present invention, there is provided above-mentioned synthetic method prepares the creatinol phosphate of synthesis.
In the still another embodiment of the present invention, there is provided above-mentioned synthetic method is in synthesis creatinol phosphate is prepared
Application.
Explanation is further explained to the present invention with comparative example by the following examples, but does not form the limit to the present invention
System.
Embodiment 1：
(1) ethanol of 300g 95%, 25g distilled water are sequentially added into reactors of the 1L with mechanical agitator, is then passed to
Carbon dioxide, 80g lime nitrogens are added in reaction solution under stirring, lime nitrogen continues to be passed through titanium dioxide after adding
Carbon stops reaction, filtering, obtains the ethanol solution 256g of cyanamide to pH=8.In whole course of reaction, pass through circulator bath
Controlling reaction temperature is below 50 DEG C；
(2) ethanol of 128g 95% and 32g 2- (methylamino) ethanol are added in the reactor with mechanical agitator, is added
It is 6 to enter the phosphorus acid for adjusting pH of 52g 85%, and step (1) solution is added dropwise in reaction system under the conditions of 60 DEG C, directly reacted
To white creatinol calcium phosphate precipitation.Filtering, absolute ethyl alcohol washing, vacuum drying creatinol phosphate 68g is (with 2- (first ammonia
Base) alcohol meter, yield 74%).
The product that it can be seen from Fig. 1 and Fig. 2 prepared by the present invention is creatinol phosphate, is drawn by Fig. 3, by efficient
Liquid chromatogram can be seen that the present invention prepares creatinol phosphoric acid purity salt higher than 95% (wherein, the as creatinol phosphoric acid of component 1
Salt, liquid phase chromatogram condition are：Detection wavelength 207nm；Pure methanol/water=7 of mobile phase：3；C18 posts；Test sample purity is higher than
95%).
Embodiment 2：
(1) ethanol of 320g 95%, 20g distilled water are sequentially added into reactors of the 1L with mechanical agitator, is then passed to
Carbon dioxide, 96g lime nitrogens are added in reaction solution under stirring, lime nitrogen continues to be passed through titanium dioxide after adding
Carbon stops reaction, filtering, obtains the ethanol solution 258g of cyanamide to pH=8.In whole course of reaction, pass through circulator bath
Controlling reaction temperature is below 50 DEG C；
(2) ethanol of 128g 95% and 32g 2- (methylamino) ethanol are added in the reactor with mechanical agitator, is added
It is 6 to enter the phosphorus acid for adjusting pH of 52g 85%, and step (1) solution is added dropwise in reaction system under the conditions of 60 DEG C, directly reacted
To white creatinol calcium phosphate precipitation.Filtering, absolute ethyl alcohol washing, vacuum drying creatinol phosphate 69g is (with 2- (first ammonia
Base) alcohol meter, yield 75%).
Embodiment 3：
(1) ethanol of 300g 95%, 20g distilled water are sequentially added into reactors of the 1L with mechanical agitator, is then passed to
Carbon dioxide, 80g lime nitrogens are added in reaction solution under stirring, lime nitrogen continues to be passed through titanium dioxide after adding
Carbon stops reaction, filtering, obtains the ethanol solution 250g of cyanamide to pH=7.5.In whole course of reaction, pass through recirculated water
Controlling reaction temperature is bathed below 50 DEG C；
(2) ethanol of 160g 95% and 40g 2- (methylamino) ethanol are added in the reactor with mechanical agitator, is added
It is 6 to enter the phosphorus acid for adjusting pH of 64g 85%, and step (1) solution is added dropwise in reaction system under the conditions of 60 DEG C, directly reacted
To white creatinol calcium phosphate precipitation.Filtering, absolute ethyl alcohol washing, vacuum drying creatinol phosphate 69g is (with 2- (first ammonia
Base) alcohol meter, yield 60%).
Embodiment 4：
(1) ethanol of 350g 95%, 20g distilled water are sequentially added into reactors of the 1L with mechanical agitator, is then passed to
Carbon dioxide, 80g lime nitrogens are added in reaction solution under stirring, lime nitrogen continues to be passed through titanium dioxide after adding
Carbon stops reaction, filtering, obtains the ethanol solution 260g of cyanamide to pH=8.In whole course of reaction, pass through circulator bath
Controlling reaction temperature is below 50 DEG C；
(2) ethanol of 128g 95% and 32g 2- (methylamino) ethanol are added in the reactor with mechanical agitator, is added
It is 5 to enter the phosphorus acid for adjusting pH of 59g 85%, and step (1) solution is added dropwise in reaction system under the conditions of 60 DEG C, directly reacted
To white creatinol calcium phosphate precipitation.Filtering, absolute ethyl alcohol washing, vacuum drying creatinol phosphate 60g is (with 2- (first ammonia
Base) alcohol meter, yield 65%).
Embodiment 5：
(1) ethanol of 300g 95%, 25g distilled water are sequentially added into reactors of the 1L with mechanical agitator, is then passed to
Carbon dioxide, 90g lime nitrogens are added in reaction solution under stirring, lime nitrogen continues to be passed through titanium dioxide after adding
Carbon stops reaction, filtering, obtains the ethanol solution 261g of cyanamide to pH=8.In whole course of reaction, pass through circulator bath
Controlling reaction temperature is below 50 DEG C；
(2) ethanol of 128g 95% and 32g 2- (methylamino) ethanol are added in the reactor with mechanical agitator, is added
It is 7 to enter the phosphorus acid for adjusting pH of 50g 85%, and step (1) solution is added dropwise in reaction system under the conditions of 60 DEG C, directly reacted
To white creatinol calcium phosphate precipitation.Filtering, absolute ethyl alcohol washing, vacuum drying creatinol phosphate 65g is (with 2- (first ammonia
Base) alcohol meter, yield 71%).
Embodiment 6：
(1) ethanol of 300g 95%, 20g distilled water are sequentially added into reactors of the 1L with mechanical agitator, is then passed to
Carbon dioxide, 100g lime nitrogens are added in reaction solution under stirring, lime nitrogen continues to be passed through dioxy after adding
Change carbon to pH=8, stop reaction, filtering, obtain the ethanol solution 266g of cyanamide.In whole course of reaction, pass through recirculated water
Controlling reaction temperature is bathed below 50 DEG C；
(2) ethanol of 128g 95% and 32g 2- (methylamino) ethanol are added in the reactor with mechanical agitator, is added
It is 6 to enter the phosphorus acid for adjusting pH of 55g 85%, and step (1) solution is added dropwise in reaction system under the conditions of 70 DEG C, directly reacted
To white creatinol calcium phosphate precipitation.Filtering, absolute ethyl alcohol washing, vacuum drying creatinol phosphate 62g is (with 2- (first ammonia
Base) alcohol meter, yield 68%).
Comparative example 1：
(1) 64g 2- (methylamino) ethanol and 200g methanol are first added in the reactor of 1L belt stirrers, measures 48g ice
Acetic acid is placed in standby in dropping funel.While stirring, glacial acetic acid is added dropwise dropwise, pH value of solution is measured to 6 with pH test paper.Measure
30% cyanamide aqueous solution 135g is equally placed in dropping funel, and it is added dropwise into reaction slowly together with remaining glacial acetic acid
Device, after the completion of reaction, decompression boils off 70% or so solvent, cold filtration, obtains the creatinol acetate of white；
(2) solid that step (1) obtains is added directly into the methanol containing 200g, all dissolved under the conditions of 50 DEG C
Afterwards, 85.0% phosphatase 79 1g is added, stirring has big calorimetric to release, and white sticky solid is obtained after cooling, and decompression filters, and uses
After a small amount of methanol washing, creatinol phosphate is obtained, is dried in vacuo, obtains creatinol phosphate 110g (with 2- (methylamino) ethanol
Meter, yield 60%).
As a result show：Existing synthesis work is substantially better than using technical scheme synthesis creatinol phosphate cost
Skill.Embodiment is compared with comparative example, it was demonstrated that single cyanogen of the core of technical solution of the present invention directly using ethanol as reaction dissolvent
After amine ethanol solution, phosphoric acid also serves as precipitating reagent as regulating acid agent, directly obtains creatinol phosphate, avoids existing technique
The washing process of dehydration by evaporation and salt, improve the purity and yield of product.
The preferred embodiment of the application is the foregoing is only, is not limited to the application, for the skill of this area
For art personnel, the application can have various modifications and variations.It is all within spirit herein and principle, made any repair
Change, equivalent substitution, improvement etc., should be included within the protection domain of the application.
Claims (10)
1. a kind of phosphatic synthetic method of creatinol, it is characterised in that as follows including step：
(1) lime nitrogen is added in ethanol and water mixed solution under carbon dioxide atmosphere, is continually fed into carbon dioxide and causes instead
PH value of solution is answered to 7.5~8.5, filter cyanamide ethanol solution；
(2) concentrated phosphoric acid regulation pH to 5~7 is added into ethanol and 2- (methylamino) ethanol solution, in 50~70 DEG C of temperature conditionss
Under the ethanol solution of cyanamide in step (1) is added dropwise thereto, react to obtain white creatinol calcium phosphate precipitation, purify to obtain muscle
Alcohol phosphate.
2. a kind of phosphatic synthetic method of creatinol as claimed in claim 1, it is characterised in that ethanol, stone in step (1)
The mass ratio (10~20) of grey nitrogen and water：(3~5)：(1~2), preferably 15：4：1；The reaction solution pH is 8.
A kind of 3. phosphatic synthetic method of creatinol as claimed in claim 1, it is characterised in that the quality of the ethanol point
Number is 95%, the nitrogen content of lime nitrogen>20%.
4. a kind of phosphatic synthetic method of creatinol as claimed in claim 1, it is characterised in that rate-determining steps (1) react
Temperature≤50 DEG C, it is preferred that using circulator bath mode controlling reaction temperature≤50 DEG C.
A kind of 5. phosphatic synthetic method of creatinol as claimed in claim 1, it is characterised in that the quality of the concentrated phosphoric acid
Fraction is 85%.
A kind of 6. phosphatic synthetic method of creatinol as claimed in claim 1, it is characterised in that second in the step (2)
The mass ratio of alcohol, 2- (methylamino) ethanol and phosphoric acid is (18~20)：(4~6)：(7~9), preferably 20：5：8；
The mass ratio of lime nitrogen and 2- (methylamino) ethanol in step (2) in step (1) is (5-6)：2, preferably 5:2.
7. a kind of phosphatic synthetic method of creatinol as claimed in claim 1, it is characterised in that adjusted in the step (2)
PH to 6 is saved, controlling reaction temperature is 60 DEG C.
8. a kind of phosphatic synthetic method of creatinol, it is characterised in that as follows including step：
(1) in the reactor with mechanical agitator, 95% second alcohol and water is added, then passes to carbon dioxide, in stirring shape
By lime nitrogen (nitrogen content under state>20%) it is added in reaction solution, lime nitrogen continues to be passed through carbon dioxide to pH after adding
=8, stop reaction, filtering, obtain the ethanol solution of cyanamide, in whole course of reaction, pass through circulator bath control reaction temperature
Degree is below 50 DEG C；
(2) 95% ethanol and 2- (methylamino) ethanol are added in the reactor with mechanical agitator, 85% phosphoric acid is added and adjusts
It is 6 to save pH, and the ethanol solution of the cyanamide in step (1) is added dropwise in reaction system under the conditions of 60 DEG C, directly reacted
To white creatinol calcium phosphate precipitation, filtering, absolute ethyl alcohol washing, vacuum drying, creatinol phosphate is obtained；
Wherein, the mass ratio of 95% ethanol, lime nitrogen and water is 15 in step (1)：4：1；
The mass ratio of 95% ethanol, 2- (methylamino) ethanol and phosphoric acid is 20 in step (2)：5：8；
The mass ratio of lime nitrogen and 2- (methylamino) ethanol in step (2) is 5 in step (1):2.
9. any one of the claim 1-8 synthetic methods prepare the creatinol phosphate of synthesis.
10. any one of the claim 1-8 synthetic methods are preparing the application in synthesizing creatinol phosphate.
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1325025A (en) * | 1969-12-08 | 1973-08-01 | Reichhold Albert Chemie Ag | Methods of cementing solid materials |
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| CN106117087A (en) * | 2016-07-13 | 2016-11-16 | 启东瑞华药业有限公司 | A kind of creatinol method for production of phosphate salt |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| GB1325025A (en) * | 1969-12-08 | 1973-08-01 | Reichhold Albert Chemie Ag | Methods of cementing solid materials |
| US5017355A (en) * | 1988-05-18 | 1991-05-21 | Nippon Carbide Kogyo Kabushiki Kaisha | Process for producing cyanamide |
| CN101671282A (en) * | 2009-10-16 | 2010-03-17 | 天津天成制药有限公司 | Preparation method for creatinol sulphate |
| CN102070535A (en) * | 2011-02-23 | 2011-05-25 | 江苏蓝丰生物化工股份有限公司 | Preparing method for synthesizing sanmate from calcium cyanamide |
| CN103011200A (en) * | 2012-12-13 | 2013-04-03 | 黄河三角洲京博化工研究院有限公司 | Preparation method of high-concentration cyanamide solution |
| CN106117087A (en) * | 2016-07-13 | 2016-11-16 | 启东瑞华药业有限公司 | A kind of creatinol method for production of phosphate salt |
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