CN104418889A - New benfotiamine synthesis method - Google Patents
New benfotiamine synthesis method Download PDFInfo
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- CN104418889A CN104418889A CN201310373020.9A CN201310373020A CN104418889A CN 104418889 A CN104418889 A CN 104418889A CN 201310373020 A CN201310373020 A CN 201310373020A CN 104418889 A CN104418889 A CN 104418889A
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- benfotiamine
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Abstract
The invention provides a new benfotiamine synthesis method, the synthetic route is as follows: using a thiamine nitrate solution, phosphoric acid, benzoyl chloride and phosphorus trichloride as raw materials, adding ethanol solvent into a reactor, adding thephosphoric acid and the phosphorus trichloride for reaction for producing a pyrophosphoric acid solution and hydrogen chloride gas, reacting the obtained hydrogen chloride gas with the thiamine nitrate for producing a thiamine hydrochloride solution, and reacting the thiamine hydrochloride solution with the pyrophosphoric acid to obtain a monophosphothiamine crude product, dissolving the monophosphothiamine crude product, adding the benzoyl chloride, mixing, after the completion of the reaction, filtering, concentrating the filtrate, adjusting the pH to be alkaline to obtain benfotiamine crystals.
Description
Technical field
The invention belongs to the improvement of organic compound manufacture method, be specifically related to a kind of benfotiamine and improve one's methods.
Background technology
Benfotiamine is the fat-soluble derivant of VitB1, is a kind of derivative of VITMAIN B1 of synthesis, improves the shortcoming that VITMAIN B1 bioavailability is low, improves the concentration of VitB1 in blood and tissue, and then improves curative effect.It is mainly used in the treatment of neuropathy, sciatica and other metabolic disturbance relative disease.Benfotiamine extensively goes on the market in the U.S., Europe, Japan etc. all over the world as VITMAIN B1 supplement, and requirement increases day by day.
But in the synthetic method of benfotiamine, be mostly take thiamine hydrochloride as starting raw material, react with tetra-sodium and generate Vitamin B1 Phosphate, then carry out reaction with Benzoyl chloride and generate benfotiamine.In this process, the utilization ratio of thiamine hydrochloride is not but very high, and wastes a large amount of raw materials in the independent production of tetra-sodium, adds cost.
Summary of the invention
The object of the present invention is to provide a kind of low in the pollution of the environment, method is easy, raw material availability is high, be easy to the synthetic method of the benfotiamine of suitability for industrialized production.
For solving the problems of the technologies described above, the invention provides following scheme: a kind of benfotiamine new synthetic method, it is characterized in that synthetic route is as follows: adopt thiamine mononitrate solution, phosphoric acid, Benzoyl chloride and phosphorus trichloride are starting raw material, add alcohol solvent in the reactor, add phosphoric acid and phosphorus trichloride in confined conditions to react and produce pyrophosphate solution and hydrogen chloride gas, the hydrogen chloride gas obtained and thiamine mononitrate are carried out reaction and produces thiamine hydrochloride solution, and then thiamine hydrochloride solution and above-mentioned tetra-sodium are obtained by reacting the thick finished product of Vitamin B1 Phosphate, the thick finished product of dissolved phosphorus thiamines, add Benzoyl chloride to stir, react rear filtration, regulate pH value to alkalescence after filtrate is concentrated, obtain benfotiamine crystallization.
As the preferred version of the above-mentioned a kind of benfotiamine new synthetic method of the present invention, wherein said thiamine hydrochloride and tetra-sodium need react in airtight vacuum container.
As the preferred version of the above-mentioned a kind of benfotiamine new synthetic method of the present invention, the temperature that wherein said thiamine hydrochloride and tetra-sodium react is 100 DEG C-150 DEG C, reaction times 2-3 hour.
As the preferred version of the above-mentioned a kind of benfotiamine new synthetic method of the present invention, the mol ratio of wherein said hydrogenchloride and thiamine mononitrate is 0.1:1-1:1.
As the preferred version of the above-mentioned a kind of benfotiamine new synthetic method of the present invention, the wherein said alkalescence that is adjusted to by pH value adopts sodium hydroxide.
The present invention has at least following beneficial effect:
1, adopt relatively inexpensive thiamine mononitrate to be raw material, reduce cost;
2, the hydrogen chloride gas that reaction is produced can be used as raw material thiamine mononitrate being converted into thiamine hydrochloride, achieves the coupling of reaction.
3, the transformation efficiency of thiamine mononitrate is high, and associating yield is more than 80%.
Embodiment
Below in conjunction with embodiment, the present invention will be further described:
Embodiment one: 16.23g phosphoric acid and 12.33g phosphorus trichloride are joined in 3.6mL ethanolic soln, and be placed in encloses container, stirs and obtains pyrophosphate solution and hydrogen chloride gas after 1 hour.Imported to by the hydrogen chloride gas obtained in thiamine mononitrate solution, after abundant reaction, obtain thiamine hydrochloride solution, this thiamine mononitrate solution is that 28.19g thiamine mononitrate is dissolved in 3.6mL ethanolic soln and obtains.Then the thiamine hydrochloride solution that the tetra-sodium obtained in back and this step obtain is mixed, heat after 1 hour at the temperature of 100 DEG C, obtain Vitamin B1 Phosphate solution.Regulate its PH to 8-9 with the sodium hydroxide solution of 15% again, add 36.11g Benzoyl chloride and stir at 0-5 DEG C, observe the PH of solution to time constant, continue stirring 1 hour, regulate PH to 3-4, suction filtration, obtains benfotiamine white solid, yield 74.3%.
Embodiment two: 16.23g phosphoric acid and 12.33g phosphorus trichloride are joined in 3.6mL ethanolic soln, and be placed in encloses container, stirs and obtains pyrophosphate solution and hydrogen chloride gas after 1 hour.Imported to by the hydrogen chloride gas obtained in thiamine mononitrate solution, after abundant reaction, obtain thiamine hydrochloride solution, this thiamine mononitrate solution is that 21.24g thiamine mononitrate is dissolved in 3.6mL ethanolic soln and obtains.Then the thiamine hydrochloride solution that the tetra-sodium obtained in back and this step obtain is mixed, heat after 3 hours at the temperature of 100 DEG C, obtain Vitamin B1 Phosphate solution.Regulate its PH to 8-9 with the sodium hydroxide solution of 15% again, add 36.11g Benzoyl chloride and stir at 0-5 DEG C, observe the PH of solution to time constant, continue stirring 1 hour, regulate PH to 3-4, suction filtration, obtains benfotiamine white solid, yield 84.3%.
Embodiment three: 16.23g phosphoric acid and 12.33g phosphorus trichloride are joined in 3.6mL ethanolic soln, and be placed in encloses container, stirs and obtains pyrophosphate solution and hydrogen chloride gas after 1 hour.Imported to by the hydrogen chloride gas obtained in thiamine mononitrate solution, after abundant reaction, obtain thiamine hydrochloride solution, this thiamine mononitrate solution is that 12.36g thiamine mononitrate is dissolved in 3.6mL ethanolic soln and obtains.Then the thiamine hydrochloride solution that the tetra-sodium obtained in back and this step obtain is mixed, heat after 3 hours at the temperature of 150 DEG C, obtain Vitamin B1 Phosphate solution.Regulate its PH to 8-9 with the sodium hydroxide solution of 15% again, add 36.11g Benzoyl chloride and stir at 0-5 DEG C, observe the PH of solution to time constant, continue stirring 1 hour, regulate PH to 3-4, suction filtration, obtains benfotiamine white solid, yield 87.4%.
Claims (5)
1. a benfotiamine new synthetic method, is characterized in that synthetic route is as follows:
Adopt thiamine mononitrate solution, phosphoric acid, Benzoyl chloride and phosphorus trichloride are starting raw material, add alcohol solvent in the reactor, add phosphoric acid and phosphorus trichloride in confined conditions to react and produce pyrophosphate solution and hydrogen chloride gas, the hydrogen chloride gas obtained and thiamine mononitrate are carried out reaction and produces thiamine hydrochloride solution, and then thiamine hydrochloride solution and above-mentioned tetra-sodium are obtained by reacting the thick finished product of Vitamin B1 Phosphate, the thick finished product of dissolved phosphorus thiamines, add Benzoyl chloride to stir, react rear filtration, regulate pH value to alkalescence after filtrate is concentrated, obtain benfotiamine crystallization.
2. a kind of benfotiamine new synthetic method according to claim 1, is characterized in that: described thiamine hydrochloride and tetra-sodium need react in airtight vacuum container.
3. a kind of benfotiamine new synthetic method according to claim 1, is characterized in that: the temperature that described thiamine hydrochloride and tetra-sodium react is 100 DEG C-150 DEG C, reaction times 2-3 hour.
4. a kind of benfotiamine new synthetic method according to claim 1, is characterized in that: the mol ratio of described hydrogenchloride and thiamine mononitrate is 0.1:1-1:1.
5. a kind of benfotiamine new synthetic method according to claim 1, is characterized in that: the described alkalescence that is adjusted to by pH value adopts sodium hydroxide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310373020.9A CN104418889A (en) | 2013-08-26 | 2013-08-26 | New benfotiamine synthesis method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310373020.9A CN104418889A (en) | 2013-08-26 | 2013-08-26 | New benfotiamine synthesis method |
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| Publication Number | Publication Date |
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| CN104418889A true CN104418889A (en) | 2015-03-18 |
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| CN201310373020.9A Pending CN104418889A (en) | 2013-08-26 | 2013-08-26 | New benfotiamine synthesis method |
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| CN (1) | CN104418889A (en) |
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2013
- 2013-08-26 CN CN201310373020.9A patent/CN104418889A/en active Pending
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Application publication date: 20150318 |
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| WD01 | Invention patent application deemed withdrawn after publication |