CN103554196A - Crystallization method of sucrose-6-acetate - Google Patents
Crystallization method of sucrose-6-acetate Download PDFInfo
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- CN103554196A CN103554196A CN201310593008.9A CN201310593008A CN103554196A CN 103554196 A CN103554196 A CN 103554196A CN 201310593008 A CN201310593008 A CN 201310593008A CN 103554196 A CN103554196 A CN 103554196A
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Abstract
The invention relates to a synthesis and crystallization method of sucrose-6-acetate. The method is characterized by using sucrose and orthoester as raw materials, generating an intermediate by carrying out catalytic cyclization on the raw materials with an organic acid, then adding water and generating sucrose esters with different 4,6 loci through simple ring-opening reaction, then transferring acyl in the locus 4 to the locus 6 in the presence of tert-butylamine, using a solvent with lower boiling point to extract a reaction mixture at a lower temperature, adding methylbenzene for azeotropy and bringing little water to prevent intermolecular hydrogen bonds from being formed and affecting crystallization, adding petroleum ether under the condition of ultrasonic flow at a specific temperature to enable the sucrose-6-acetate crystal to be more regular and then using ethyl acetate for recrystallization. The method has the advantages of few reaction steps, accessible raw materials of the intermediate, mild reaction conditions, simpleness in treatment of various intermediate products, high yield, low cost and the like, solves the problems of long synthesis route, low product yield, higher production cost, heavier environmental pollution and the like of traditional chemical synthetic methods of vinpocetine and conforms to the green chemistry development trend.
Description
technical field:
The invention belongs to foodstuff additive field, it relates to a kind of method that sucrose and ortho ester be raw material synthesizing cane sugar-6-acetic ester and crystallization of take.
background technology:
Sucralose at first Shi You Britain Tate & Lyle company was researched and developed success and applied for a patent in 1976, and Hou Yu U.S. Johnson company developed jointly and produced the 80's, and 1988 start to put goods on the market.After the toxicity test and biochemical property of more than ten years, the status that FDA Food and Drug Administration (FDA) has ratified its intense sweetener on March 21st, 1998, and China Ministry of Health stipulates in the < < foodstuff additive use use standard > > issuing for 1997, can be at frozen beverage, fruit can, pickled vegetables, canned eight treasure porridge class, bakery product, vinegar, soy sauce, beverage class, in assembled alcoholic drinks, use this product, permission addition is 0.25g/kg, at jam, microwave popcorn, spice sauce, fermented wine, addition in jelly is 0.4～0.9.
Cane sugar-6-acetic ester is an important intermediate in synthesizing trichloro process, and the synthetic quality of cane sugar-6-acetic ester is directly connected to quality and the productive rate of product.And generally cane sugar-6-acetic ester is not crystallized out in the process of modern synthesizing trichloro, but one kettle way directly joins next reaction the mixing solutions of cane sugar-6-acetic ester, and this method not only makes side reaction increase, and can cause the sugar in next step a large amount of carbonization solution of chlorination.In sum, seldom there are document or patent to relate to the crystallization of cane sugar-6-acetic ester both at home and abroad now.And the crystallization of carbohydrate is a very meticulous preparation process, in crystallisation process, a little variation of ambient conditions all may affect crystallization, such as temperature, concentration, viscosity, velocity of flow, solvent etc.Or else some carbohydrate drops in the situation of crystal seed and is difficult to crystallization, and the compound of some crystallization need to just can be born the crystal of comparison rule in the situation that of microwave concussion or excusing from death.And the present invention aims at sucrose-6-to crystallize out, not only can obtain more highly purified product and be used for synthesizing trichloro, can also be as the raw material of other building-up reactionss.The present industrial several different methods synthesizing trichloro that has.For example, English Patent (GB1543167) is reported a kind of full radical protection method, this method is that 8 of sucrose hydroxyls are all protected, then be specifically released in 4, the blocking group of 1 ' 6 ' three positions, carrying out follow-up chlorination, the method comprises tritylation, acetylize, detritylation, acetyl group migration, the step such as selective chlorination and deacetylation, this method is method used while starting synthesizing trichloro most, the sucralose purity of preparation is high in this way, but during can use more expensive pyridine and trityl compound, route is also longer.Sucralose is prepared in industry now hardly in this way.Relative with full radical protection method is single radical protection method, this method is first synthesis of sucrose-6-esters, again through chloro, the subsequent disposal such as deprotection obtain Sucralose, for example United States Patent (USP) (US4380476) and (US4612373) organotin method be also the industrial process of a kind of outbalance in single radical protection method, United States Patent (USP) (US4950746) has been reported reacting of Dibutyltin oxide and sucrose, methyl alcohol is made solvent, obtain intermediate product 1, 3-bis--(6-O-sucrose)-1, 1, 3, 3-tetrabutyldistannoxane (DBSS), again with anhydride reaction, obtain sucrose-6-ester.This method is constantly modified subsequently.For example (US5023329) reported with DMF and made solvent, and hexanaphthene is done cosolvent, react at a certain temperature and prepared DBSS with Dibutyltin oxide, then with anhydride reaction, prepare sucrose-6-ester.(US5089608) reported Dibutyltin oxide prior to ethylene glycol in reflux in toluene, obtain intermediate product, then react in DMF with sucrose, then with acetic anhydride, finally process and obtain sucrose-6-ester.Along with updating of method, be more and more applicable to industrialization, the recovery of Dibutyltin oxide also can reach very gratifying effect.But along with the enhancing that green safety is seen, the chemical process of bringing heavy metal element into is in waning favor with the people.Ortho ester method is a kind of comparatively good single functional group method, prepares in the process of sucrose-6-ester, and reaction conditions is gentle, does not relate to high score high pressure, the reactant cheapness that is also easy to get very much, and solvent DMF is less expensive product.This method is used in the present invention.Other preparation methods of Sucralose also have raffinose method, and raffinose is trisaccharide, because the Gal base of raffinose is just in time positioned on sucrose C-6 position, are serving as the natural blocking group of C-6.Therefore, raffinose can directly carry out selective chlorination make 6,4 ' ', 1 ' ', 6 ' '-tetrachloro raffinose, then remove Gal-6-Cl through alpha galactosides enzymic hydrolysis and obtain Sucralose.It's a pity that current raffinose also fails suitability for industrialized production, can not meet the requirement of suitability for industrialized production Sucralose to raw material raffinose.In addition also have the synthetic Sucralose of preparing of enzyme-chemically method, the advantage of this method is that the colleges and universities of enzyme are selected and yield is higher, and shortcoming is separated difficulty, and the cultivation of bacterium producing multi enzyme preparation, and investment in fixed assets is large.
The present invention passes through single functional group method synthesizing cane sugar-6-acetic ester, and by a series of follow-up means, prepares the single crystal of cane sugar-6-acetic ester.This synthetic method synthetic route is short, and raw material is easy to get, and synthetic cost is lower, to the advantage such as environment-friendly.
summary of the invention:
The present invention seeks to develop and a kind ofly take easy, the condition that sucrose and ortho ester be raw material synthesizing cane sugar-6-acetic ester and crystallization and be easy to the method for controlling, productive rate is higher.
1. the present invention adopts a kind of synthetic method of cane sugar-6-acetic ester, its synthetic route as shown in Figure 1:
2. in said synthesis route, each step reaction processing condition are as follows:
(1) get appropriate sucrose with anhydrous 1,1,2-trichloroethane dissolves, and is then warmed up to 50 ℃ sucrose is dissolved rapidly, after sucrose dissolved, disposable ortho-acetate and the tosic acid of adding, stirring reaction 2.5-3.5 hour, use chloroform methanol solution to make developping agent, 5% sulfuric acid methanol solution is made developer and is carried out a plate observation, after question response finishes, add appropriate deionized water, stir 1-2 hour.Add again TERTIARY BUTYL AMINE appropriate, continue to stir 1-2 hour, obtain mixture.
(2) mixture is first extracted out and is surpassed at 1/2 to 2/3 o'clock until solvent through underpressure distillation, filters and removes the salt generating, solvent vinyl trichloride washed twice for filter residue, merging filtrate.The toluene that adds 0.5 times of liquor capacity, stir, then at the temperature higher than 80oC not, remove solvent under reduced pressure, until solvent, extract out within 1/2 to 2/3 o'clock, adding crystal seed and stop continuing evaporating solvent, put into excusing from death wave device, control liquid flow velocity, crystallization control temperature is between 25 ℃ to 35 ℃, and it is more than 98.0% crystal that the crystal obtaining obtains purity with re-crystallizing in ethyl acetate after filtration.
Synthetic and the crystallization of cane sugar-6-acetic ester of the present invention has the following advantages and gives prominence to effect:
(1) take that sucrose and ortho ester are prepared cane sugar-6-acetic ester crystal as initiator and had that synthetic route is short, reaction conditions is easy to control, yield is higher, simple to operate, overcome traditional chemical synthesizing cane sugar-6-acetic ester method synthetic route long, bring heavy metal ion into, the problems such as solvent is expensive, and the large and cost of operation easier is higher.
(2) agents useful for same of the present invention has no side effect, and can environment not produced and be polluted, and meets the trend of Green Chemistry development, can be used as a kind of method that obtains purer cane sugar-6-acetic ester.
accompanying drawing explanation:
Fig. 1 is the synthetic route chart of cane sugar-6-acetic ester.
embodiment:
Further illustrate in the following embodiments the present invention, this does not limit the scope of the invention.
embodiment 1
Synthesizing of cane sugar-6-acetic ester adds 65 mL1 in the three-necked bottle that fills 10 g sucrose, 1,2-trichloroethane, and heated and stirred makes it to dissolve completely, and Heating temperature is no more than 80 ℃.Then disposable 2.8 g compound trimethyl orthoacetates and the 0.06g tosic acid of adding, at room temperature stirring reaction is 3 hours.Silica-gel plate following response process for reaction whole process, the chloroform methanol solution that developping agent is 3:1, after having reacted, adds 4ml deionized water, continues to stir 2 hours until reaction finishes under room temperature.Then add 1ml TERTIARY BUTYL AMINE, under room temperature, continue to stir one hour until reaction finishes, obtain mixed solution.Mixed solution is first extracted out and is surpassed at 1/2 to 2/3 o'clock until solvent through underpressure distillation, filters and removes the salt generating, a small amount of solvent vinyl trichloride washed twice for filter residue, merging filtrate.Add 30ml toluene, stir, then, at the temperature higher than 80oC not, remove solvent under reduced pressure, until solvent, extract out to surpass and add crystal seed and stop continuing evaporating solvent for 1/2 to 2/3 o'clock.Add sherwood oil 10ml and put into excusing from death wave device, control liquid flow velocity, crystallization control temperature is 30 ℃, and it is more than 98.0% crystal that the crystal obtaining obtains purity with re-crystallizing in ethyl acetate after filtration, mother liquor, through applying mechanically continuation crystalline sucrose-6-acetic ester, reaches the object of saving solvent.
embodiment 2
Synthesizing of cane sugar-6-acetic ester.In the three-necked bottle that fills 10 g sucrose, add 65 mL1,1,2-trichloroethane, heated and stirred makes it to dissolve completely, and Heating temperature is no more than 80 ℃.Then disposable 3.2g compound triethly orthoacetate and the 0.06g tosic acid of adding, at room temperature stirring reaction is 3 hours.Silica-gel plate following response process for reaction whole process, the chloroform methanol solution that developping agent is 3:1, after having reacted, adds 4ml deionized water, continues to stir 2 hours until reaction finishes under room temperature.Then add 1ml TERTIARY BUTYL AMINE, under room temperature, continue to stir one hour until reaction finishes, obtain mixing solutions.Mixture is first extracted out and is surpassed at 1/2 to 2/3 o'clock until solvent through underpressure distillation, filters and removes the salt generating, a small amount of solvent vinyl trichloride washed twice for filter residue, merging filtrate.Add 30ml toluene, stir, then, at the temperature higher than 80oC not, remove solvent under reduced pressure, until solvent, extract out to surpass and add crystal seed and stop continuing evaporating solvent for 1/2 to 2/3 o'clock.Add sherwood oil 10ml and put into excusing from death wave device, control liquid flow velocity, crystallization control temperature is 30 ℃, and it is more than 98.0% crystal that the crystal obtaining obtains purity with re-crystallizing in ethyl acetate after filtration, mother liquor, through applying mechanically continuation crystalline sucrose-6-acetic ester, reaches the object of saving solvent.
Claims (5)
1. the present invention is intended to develop a kind of crystallization method of cane sugar-6-acetic ester, it is characterized in that take that sucrose and ortho-acetate are as raw material, under organic acid catalysis, carry out esterification, the functional group that participates in open loop and organic bases participation through over-churning annulation, water shifts conventional processing acquisition cane sugar-6-acetic ester.
2. according to right 1, require described method, its synthetic route is as shown in Figure of description 1.
3. according to right 2, require described synthetic route, the ortho-acetate of using in the esterification that sucrose and ortho-acetate carry out is trimethyl orthoacetate or triethly orthoacetate, organic acid used is tosic acid, the organic bases of using is TERTIARY BUTYL AMINE, solvent used is 1,1,2-trichloroethane, reaction is carried out at normal temperatures.
4. according to right 2, require described synthetic route, the processing condition of compound IV ring-closure reaction are: get appropriate sucrose with anhydrous 1,1,2-trichloroethane dissolves, then being warmed up to 50 ℃ dissolves rapidly sucrose, after sucrose dissolved, disposable ortho-acetate and the tosic acid of adding, stirring reaction 2.5-3.5 hour, use 5% sulfuric acid methanol solution to make developer and carry out a plate and observe, after finishing, question response adds appropriate deionized water, stir 1-2 hour, add again TERTIARY BUTYL AMINE appropriate, continue to stir 1-2 hour, obtain mixture.
5. according to right 2, require described synthetic route, the operation steps of the crystallization of compound cane sugar-6-acetic ester is as follows: mixture is first extracted out over 1/2 to 2/3 o'clock until solvent through underpressure distillation, filter and remove the salt generating, solvent 1 for filter residue, 1, 2-trichloroethane washed twice, merging filtrate, the toluene that adds 0.5 times of liquor capacity, stir, then at the temperature higher than 80oC not, remove solvent under reduced pressure, until solvent, extract out to surpass and add crystal seed and stop continuing evaporating solvent for 1/2 to 2/3 o'clock, put into excusing from death wave device, control liquid flow velocity, crystallization control temperature is between 25 ℃ to 35 ℃, it is more than 98.0% crystal that the crystal obtaining obtains purity with re-crystallizing in ethyl acetate after filtration.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105254684A (en) * | 2015-11-03 | 2016-01-20 | 浙江新和成股份有限公司 | Preparation method of sucrose-6-acetate |
| CN106749440A (en) * | 2016-12-07 | 2017-05-31 | 广西科技大学 | It is a kind of by sucrose and the method for crystallising of the acetic acid esters of ortho-acetate synthesis of sucrose 6 |
| CN106946956A (en) * | 2017-03-16 | 2017-07-14 | 浙江新和成股份有限公司 | A kind of recrystallization method of acetic acid esters of sucrose 6 and its application |
| CN110563780A (en) * | 2019-08-30 | 2019-12-13 | 山东新和成精化科技有限公司 | Post-treatment method of sucralose chlorination liquid and application of sucralose chlorination liquid in preparation of sucralose |
| CN113214330A (en) * | 2021-05-13 | 2021-08-06 | 安徽金禾化学材料研究所有限公司 | Purification and chlorination process of sucrose-6-ethyl ester |
| CN116217635A (en) * | 2023-03-02 | 2023-06-06 | 福建桦智工程技术有限公司 | Deacidifying and purifying method for sucrose-6-acetate |
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| CN101041676A (en) * | 2007-04-18 | 2007-09-26 | 江苏强盛化工有限公司 | Preparation method of saccharose-6-acetic acid esters |
| CN101367848A (en) * | 2007-08-15 | 2009-02-18 | 常州市牛塘化工厂有限公司 | Preparation method for sucrose-6- ethyl ester |
| CN102690299A (en) * | 2012-05-25 | 2012-09-26 | 浙江海森药业有限公司 | Method for preparing sucralose-6-acetate by tandem reaction |
| CN102816188A (en) * | 2012-08-13 | 2012-12-12 | 南通市常海食品添加剂有限公司 | Production technology of sucralose |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101041676A (en) * | 2007-04-18 | 2007-09-26 | 江苏强盛化工有限公司 | Preparation method of saccharose-6-acetic acid esters |
| CN101367848A (en) * | 2007-08-15 | 2009-02-18 | 常州市牛塘化工厂有限公司 | Preparation method for sucrose-6- ethyl ester |
| CN102690299A (en) * | 2012-05-25 | 2012-09-26 | 浙江海森药业有限公司 | Method for preparing sucralose-6-acetate by tandem reaction |
| CN102816188A (en) * | 2012-08-13 | 2012-12-12 | 南通市常海食品添加剂有限公司 | Production technology of sucralose |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105254684A (en) * | 2015-11-03 | 2016-01-20 | 浙江新和成股份有限公司 | Preparation method of sucrose-6-acetate |
| CN105254684B (en) * | 2015-11-03 | 2019-01-01 | 浙江新和成股份有限公司 | A kind of preparation method of cane sugar-6-acetic ester |
| CN106749440A (en) * | 2016-12-07 | 2017-05-31 | 广西科技大学 | It is a kind of by sucrose and the method for crystallising of the acetic acid esters of ortho-acetate synthesis of sucrose 6 |
| CN106749440B (en) * | 2016-12-07 | 2019-07-02 | 广西科技大学 | A kind of method for crystallising by sucrose and ortho-acetate synthesizing cane sugar-6-acetic ester |
| CN106946956A (en) * | 2017-03-16 | 2017-07-14 | 浙江新和成股份有限公司 | A kind of recrystallization method of acetic acid esters of sucrose 6 and its application |
| CN106946956B (en) * | 2017-03-16 | 2020-06-09 | 浙江新和成股份有限公司 | Recrystallization method and application of sucrose-6-acetate |
| CN110563780A (en) * | 2019-08-30 | 2019-12-13 | 山东新和成精化科技有限公司 | Post-treatment method of sucralose chlorination liquid and application of sucralose chlorination liquid in preparation of sucralose |
| CN110563780B (en) * | 2019-08-30 | 2020-08-14 | 山东新和成精化科技有限公司 | Post-treatment method of sucralose chlorination liquid and application of sucralose chlorination liquid in preparation of sucralose |
| CN113214330A (en) * | 2021-05-13 | 2021-08-06 | 安徽金禾化学材料研究所有限公司 | Purification and chlorination process of sucrose-6-ethyl ester |
| CN116217635A (en) * | 2023-03-02 | 2023-06-06 | 福建桦智工程技术有限公司 | Deacidifying and purifying method for sucrose-6-acetate |
| CN116217635B (en) * | 2023-03-02 | 2023-09-01 | 福建桦智工程技术有限公司 | Deacidifying and purifying method for sucrose-6-acetate |
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Application publication date: 20140205 |