CN104031038A - Method for preparing vitamin B1 hydrochloride with thiol thiamine - Google Patents
Method for preparing vitamin B1 hydrochloride with thiol thiamine Download PDFInfo
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- CN104031038A CN104031038A CN201410314636.3A CN201410314636A CN104031038A CN 104031038 A CN104031038 A CN 104031038A CN 201410314636 A CN201410314636 A CN 201410314636A CN 104031038 A CN104031038 A CN 104031038A
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- thiol
- cation exchange
- exchange resin
- hydrochloride
- thiamines
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D415/00—Heterocyclic compounds containing the thiamine skeleton
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Abstract
The invention discloses a method for preparing vitamin B1 hydrochloride with thiol thiamine in the field of the medical technology. Vitamin B1 midbody thiol thiamine serves as the raw material. The preparing method includes the following steps that after thiol thiamine reaction liquid which is oxidized through hydrogen peroxide is diluted with proper purified water, dissociation and exchange are conducted through cation exchange resin column; proper purified water is used for washing the cation exchange resin column until a plurality of drips of barium chloride solutions with the content of five percent are added to washing liquid and white barium sulfate precipitates cannot be seen with the naked eyes; an eluant is used for eluting the cation exchange resin column until an effluent below does not contain the vitamin B1 any more; the cation exchange resin is 732 strong-acid cation exchange resin; the use amount of the cation exchange resin is one to six times of the total mass of the thiol thiamine; the eluent is diluted hydrochloric acid with the content of 5-20 percent. According to the method for preparing the vitamin B1 hydrochloride with the thiol thiamine, foreign ions are not generated, environmental friendliness is achieved, the reaction conditions are mild, the reaction speed is high, the conversion rate and selectivity are high, the service life of the catalyst, namely the cation exchange resin is long, and the cation exchange resin can be easily recycled and regenerated.
Description
Technical field
The one thiol thiamines the present invention relates in medical technical field is prepared vitamins B
1the method of hydrochloride.
Background technology
VITMAIN B1 is water-soluble vitamins, and the same with the VITAMIN in all B family, unnecessary VITMAIN B1 can not be stored in body, and can excrete completely.So, must supplement every day.Participate in vivo the metabolism of carbohydrate.VITMAIN B1 is called as psychogenic VITAMIN, and this is because VITMAIN B1 has desirable influence to nervous tissue and the mental status; VITMAIN B1 intramuscular injection absorbs fast and completely, oral absorption is limited, stores in vivo lessly, and excessive part is discharged by kidney with original shape.VITMAIN B1 forms phosphorylated thiamine in vivo, the oxidative decarboxylation of pyruvic acid, α-ketoglutaric acid reaction in involved in sugar metabolism, carbohydrate metabolism generation obstacle when shortage.Also with keep the normal function of the systems such as cardiovascular, the digestion of nerve conduction and skin relevant.
China is VITAMIN big producing country and trade exports big country, have the title of VITAMIN production base, the world.But owing to being subject to the impact of international economy overall situation continued downturn, the first half of the year in 2012, VITAMIN acceleration rate of export is slow, single kind export volume generally declines.2012,9.23 ten thousand tons of VITAMIN export volumes in the first half of the year, declined 4.42% over the same period last year, and export amount of money reaches 10.24 hundred million dollars, increases by 8.9% on a year-on-year basis, and wherein vitamin B complex export price rises three one-tenth.The main manufacturing enterprise of VITMAIN B1 is the new medicine company of Central China, Hubei medicine company and sky, Jiangxi, and world market occupation rate approximately reaches 70% left and right.The first half of the year, VITMAIN B1 export volume was 2465 tons, fell 13.73% on a year-on-year basis, and export amount of money is 6,831 ten thousand dollars, increases by 51.32% on a year-on-year basis, and outlet average price is 27.7 dollars/kilogram, increases by 75.4% on a year-on-year basis.
Industrial production vitamin b1 hydrochloride, generally all adopting thiol thiamines is intermediate, become VITMAIN B1 vitriol through hydrogen peroxide oxidation, then utilize the difference of the solubleness of vitamin b1 nitrate and VITMAIN B1 vitriol, become vitamin b1 nitrate to separate out VITMAIN B1 sulfate conversion, convert it into vitamin b1 hydrochloride crude product with hydrogenchloride ethanol or methanol solution again, final refining obtains vitamin b1 hydrochloride finished product.This processing method adopts nitric acid and hydrochloric acid to be strong acid, after salify, just utilize they VITMAIN B1 salt solubleness in methyl alcohol or ethanol difference and reach the conversion of VITMAIN B1 from nitrate to hydrochloride, so in vitamin b1 hydrochloride finished product, be difficult to Ex-all nitrate ion (NO
3-), easily in vitamin b1 hydrochloride finished product, check out brown ring quality problem, that is: nitrate ion (NO in finished product
3-) limitation exceed standard, do not reach the requirement of American Pharmacopeia and British Pharmacopoeia.Prior art is carrying out nitrate in hydrochloride conversion reaction in addition, the hydrochloric acid methanol using or ethanol use chlorsulfonic acid to prepare, and because chlorsulfonic acid ingress of air easily decomposes, emit a large amount of hydrogen chloride gas,, so also there is larger problem aspect environmental protection in serious environment pollution.
In patent CN1459449 A, the novel method of preparing vitamin b1 hydrochloride with thiol thiamines is that vitamin B 1 intermediate thiol thiamines is raw material, after hydrogen peroxide oxidation generates VITMAIN B1 vitriol, add bariumchloride to react with it, directly complete by VITMAIN B1 vitriol and carried out vitamin b1 nitrate to hydrochloride to the conversion recycling hydrochloric acid methanol of vitamin b1 hydrochloride, although there is no nitrate ion (NO in conversion process
3-), but introduced barium ion (Ba
2+), because adopt in 30% bicarbonate of ammonia in this patent in its aftertreatment and excessive barium ion (Ba
2+) filtrate generation barium carbonate sediment, attempt by filtering-depositing, barium ion (Ba
2+) Ex-all, but barium carbonate still has micro-solubleness in solution, be impossible Ex-all, and filter barium carbonate, there is certain viscosity, filter and also have certain difficulty, very not applicable industrialization, moreover, whole technique has used a large amount of mineral compound to neutralize or salt-forming reaction, cannot recovery, virtually cause whole process costs to promote and operation steps is grown and loaded down with trivial details, Zhe Shi enterprises least wish to see.Therefore, develop one thiol thiamines and prepare vitamins B
1the method of hydrochloride is new problem anxious to be resolved always.
Summary of the invention
The object of the present invention is to provide one thiol thiamines to prepare vitamins B
1the method of hydrochloride, utilize the method for catalyzing cation exchange resin synthesise vitamins B1 hydrochloride, method of the present invention has that reaction conditions gentleness, speed of reaction are very fast, transformation efficiency and selectivity is high, catalyzer Zeo-karb long service life, the easy advantage such as reclaiming.
The object of the present invention is achieved like this: one is prepared vitamins B with thiol thiamines
1the method of hydrochloride, taking vitamin B 1 intermediate thiol thiamines as raw material, this preparation method comprises the steps:
(1) by the thiol thiamines reaction solution after hydrogen peroxide oxidation with dissociating and exchange through cation exchange resin column after the dilution of appropriate purified water;
(2), with appropriate purified water washing cation exchange resin column, until be washed till washings, to add several content be 5% barium chloride solution, till the barium sulfate white precipitate that is invisible to the naked eye;
(3) with eluent wash-out cation exchange resin column, until no longer contain VITMAIN B1 in effluent liquid below;
Described Zeo-karb is 732 storng-acid cation exchange resin things; The consumption of described Zeo-karb is 1-6 times of thiol thiamines total mass; Described eluent is that content is the dilute hydrochloric acid of 5-20%; Described temperature of reaction is 10-60 DEG C; Described reaction pressure is 0.9-1.1atm.
Main points of the present invention are to prepare vitamins B with thiol thiamines
1the method of hydrochloride.One is prepared vitamins B with thiol thiamines
1the method of hydrochloride compared with prior art, inclusion-free ion produces, environmental protection, have that reaction conditions gentleness, speed of reaction are very fast, transformation efficiency and selectivity is high, catalyzer Zeo-karb long service life, the easy advantage such as reclaiming, can be widely used in medical technical field.
Brief description of the drawings
Below in conjunction with embodiment, the present invention is described in detail.
Fig. 1 is vitamin b1 hydrochloride structural formula figure.
Fig. 2 is prior art preparation method schema.
Embodiment
Below in conjunction with embodiment, the present invention is described further, and embodiment contributes to understand better the present invention, but the present invention is not limited only to following embodiment.
Embodiment mono-
Synthesizing of vitamin b1 hydrochloride:
In reaction flask, add in advance 53 mL purified water, be transferred to pH=4～5 with the vitriol oil, after adding and stirring well after thiol thiamines 7.4 g (25 mmoL) of 1/4 amount, strict temperature is controlled at 10～15 DEG C, minimum must not be lower than 8 DEG C, hydrogen peroxide 29.6 mL that continual dropping content is 34%, remaining thiol thiamines is cut into small pieces simultaneously, divide and add for 3 times, stir after 1 h, now temperature is at 15～17 DEG C, reaction solution is clear and bright, reaction is finished, add again 100 mL purified water dilute reaction solutions, the resin column of reaction solution after dilution being poured into 732 storng-acid cation exchange resins that contain 50 g dissociates and exchanges, wash this resin by approximately 1300 mL purified water again, it is 5% barium chloride solution that a small amount of washings that takes off face adds content, the white barium sulfate precipitate until be invisible to the naked eye, stop washing.Finally carrying out wash-out resin column with the dilute hydrochloric acid of content 10% dissociates and exchanges, be eluted to elutriant till TLC detects without VITMAIN B1, consumption is about 1600 mL left and right concentrate eluants, under 60 DEG C of conditions, carry out activated carbon decolorizing processing, again concentrated, finally ethanol/water=255:45 for crude product (v/v) is carried out to crystallization, filter, vacuum-drying obtains white crystals type powder vitamin b1 hydrochloride 32.08 g, in starting raw material thiol thiamines, yield 95.14%.Chemical examination detects in finished product vitamin b1 hydrochloride and can't detect nitrate ion (NO by analysis
3-) and sulfate ion (SO4
2-), meet American Pharmacopeia and British Pharmacopoeia requirement.
Embodiment bis-
Synthetic (recovery of catalyzer 732 Zeo-karbs and dilute hydrochloric acid elutriant and apply mechanically) of vitamin b1 hydrochloride:
In reaction flask, add in advance 27 mL purified water, be transferred to pH=4～5 with the vitriol oil, after adding and stirring well after thiol thiamines 3.7 g (12. 5 mmoL) of 1/4 amount, strict temperature is controlled at 10～15 DEG C, minimum must not be lower than 8 DEG C, hydrogen peroxide 15.0 mL that continual dropping content is 34%, remaining thiol thiamines is cut into small pieces simultaneously, divide and add for 3 times, stir after 1 h, now temperature is at 15～17 DEG C, reaction solution is clear and bright, reaction is finished, add again 60 mL purified water dilute reaction solutions, reaction solution after dilution is poured into the resin column (ion exchange column of using in embodiment 1 of 732 storng-acid cation exchange resins that contain 50 g, without further processing, directly use) dissociate and exchange, wash this resin by approximately 800 mL purified water again, it is 5% barium chloride solution that a small amount of washings that takes off face adds content, the white barium sulfate precipitate until be invisible to the naked eye, stop washing.Finally use dilute hydrochloric acid (the concentrated dilute hydrochloric acid out of aftertreatment in embodiment 1 of content 6.51%, unprocessed, directly use) carry out wash-out resin column and dissociate again and exchange, be eluted to elutriant till TLC detects without VITMAIN B1, consumption is about 900 mL left and right concentrate eluants, under 55 DEG C of conditions, carry out activated carbon decolorizing processing, again concentrated, finally methanol/water=130:23 for crude product (v/v) is carried out to crystallization, filter, vacuum-drying obtains white crystals type powder vitamin b1 hydrochloride 15.91 g, in starting raw material thiol thiamines, yield 94.37%.Chemical examination detects in finished product vitamin b1 hydrochloride and can't detect nitrate ion (NO by analysis
3-) and sulfate ion (SO4
2-), meet American Pharmacopeia and British Pharmacopoeia requirement.
Should be understood that, for those of ordinary skills, can be improved according to the above description or convert, and all these improvement and conversion all should belong to the protection domain of claims of the present invention.
Claims (6)
1. prepare vitamins B with thiol thiamines for one kind
1the method of hydrochloride, is characterized in that: taking vitamin B 1 intermediate thiol thiamines as raw material, this preparation method comprises the steps:
(1) by the thiol thiamines reaction solution after hydrogen peroxide oxidation with dissociating and exchange through cation exchange resin column after the dilution of appropriate purified water;
(2), with appropriate purified water washing cation exchange resin column, until be washed till washings, to add several content be 5% barium chloride solution, till the barium sulfate white precipitate that is invisible to the naked eye;
(3) with eluent wash-out cation exchange resin column, until no longer contain VITMAIN B1 in effluent liquid below.
2. one according to claim 1 is prepared vitamins B with thiol thiamines
1the method of hydrochloride, is characterized in that: described Zeo-karb is 732 storng-acid cation exchange resin things.
3. one according to claim 1 is prepared vitamins B with thiol thiamines
1the method of hydrochloride, is characterized in that: the consumption of described Zeo-karb is 1-6 times of thiol thiamines total mass.
4. one according to claim 1 is prepared vitamins B with thiol thiamines
1the method of hydrochloride, is characterized in that: described eluent is that content is the dilute hydrochloric acid of 5-20%.
5. one according to claim 1 is prepared vitamins B with thiol thiamines
1the method of hydrochloride, is characterized in that: described temperature of reaction is 10-60 DEG C.
6. one according to claim 1 is prepared vitamins B with thiol thiamines
1the method of hydrochloride, is characterized in that: described reaction pressure is 0.9-1.1atm.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410314636.3A CN104031038B (en) | 2014-07-04 | 2014-07-04 | The method of vitamin b1 hydrochloride prepared by a kind of sulphur hydroxyl thiamines |
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|---|---|---|---|
| CN201410314636.3A CN104031038B (en) | 2014-07-04 | 2014-07-04 | The method of vitamin b1 hydrochloride prepared by a kind of sulphur hydroxyl thiamines |
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| CN104031038A true CN104031038A (en) | 2014-09-10 |
| CN104031038B CN104031038B (en) | 2016-06-08 |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104817551A (en) * | 2015-05-07 | 2015-08-05 | 常州大学 | New method of preparing vitamin B1 hydrochloride |
| CN106674090A (en) * | 2016-12-23 | 2017-05-17 | 东北制药集团股份有限公司 | Method of preparing atazanavir sulfate |
| CN107501254A (en) * | 2017-08-15 | 2017-12-22 | 江西森泰药业有限公司 | The preparation technology of feed addictive vitamin B1 |
| CN110964004A (en) * | 2019-12-16 | 2020-04-07 | 江苏兄弟维生素有限公司 | Refining method of thiothiamine, thiothiamine product obtained by refining method and vitamin B1 product |
| CN117756796A (en) * | 2023-12-29 | 2024-03-26 | 江苏兄弟维生素有限公司 | Method for preparing thiamine nitrate or thiamine hydrochloride by direct oxidation of thiamine hydrochloride and application thereof |
Citations (5)
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|---|---|---|---|---|
| GB671036A (en) * | 1947-08-06 | 1952-04-30 | Merck & Co Inc | The preparation of salts of vitamin b |
| GB881855A (en) * | 1957-05-21 | 1961-11-08 | Merck & Co Inc | Elution of organic substances from ion-exchange resins |
| CN1459449A (en) * | 2002-05-22 | 2003-12-03 | 东北制药总厂 | New method of preparing ritamin B1 hydrochloride using thiohydrothiamine |
| CN101627017A (en) * | 2006-03-15 | 2010-01-13 | 帝斯曼知识产权资产管理有限公司 | Process for the manufacture of a precursor of vitamin b1 |
| CN102952126A (en) * | 2012-12-03 | 2013-03-06 | 华中药业股份有限公司 | Novel method for synthesizing vitamin B1 hydrochloride |
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2014
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Patent Citations (5)
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| GB671036A (en) * | 1947-08-06 | 1952-04-30 | Merck & Co Inc | The preparation of salts of vitamin b |
| GB881855A (en) * | 1957-05-21 | 1961-11-08 | Merck & Co Inc | Elution of organic substances from ion-exchange resins |
| CN1459449A (en) * | 2002-05-22 | 2003-12-03 | 东北制药总厂 | New method of preparing ritamin B1 hydrochloride using thiohydrothiamine |
| CN101627017A (en) * | 2006-03-15 | 2010-01-13 | 帝斯曼知识产权资产管理有限公司 | Process for the manufacture of a precursor of vitamin b1 |
| CN102952126A (en) * | 2012-12-03 | 2013-03-06 | 华中药业股份有限公司 | Novel method for synthesizing vitamin B1 hydrochloride |
Non-Patent Citations (2)
| Title |
|---|
| GERARD MOINE, ET AL.,: "《Ullmann Encyclopedia of Industrial Chemistry》", 15 October 2011, article "Vitamins, 6. B Vitamins.", pages: 234-245 * |
| SHUNICHI YAMADA, ET AL.,: "Preparation of thiamine monosalts by using anion exchange resins.", 《ANN.REPT.G.TANABE CO.LTD》, vol. 1, 31 December 1956 (1956-12-31), pages 26 - 28 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104817551A (en) * | 2015-05-07 | 2015-08-05 | 常州大学 | New method of preparing vitamin B1 hydrochloride |
| CN104817551B (en) * | 2015-05-07 | 2018-04-27 | 常州大学 | A kind of new method for preparing vitamin b1 hydrochloride |
| CN106674090A (en) * | 2016-12-23 | 2017-05-17 | 东北制药集团股份有限公司 | Method of preparing atazanavir sulfate |
| CN106674090B (en) * | 2016-12-23 | 2019-02-22 | 东北制药集团股份有限公司 | A method of preparing sulfuric acid atazanavir |
| CN107501254A (en) * | 2017-08-15 | 2017-12-22 | 江西森泰药业有限公司 | The preparation technology of feed addictive vitamin B1 |
| CN110964004A (en) * | 2019-12-16 | 2020-04-07 | 江苏兄弟维生素有限公司 | Refining method of thiothiamine, thiothiamine product obtained by refining method and vitamin B1 product |
| CN117756796A (en) * | 2023-12-29 | 2024-03-26 | 江苏兄弟维生素有限公司 | Method for preparing thiamine nitrate or thiamine hydrochloride by direct oxidation of thiamine hydrochloride and application thereof |
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| Publication number | Publication date |
|---|---|
| CN104031038B (en) | 2016-06-08 |
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