CN1453284A - Synthesis of trichlorosucrose - Google Patents

Synthesis of trichlorosucrose Download PDF

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Publication number
CN1453284A
CN1453284A CN 03126655 CN03126655A CN1453284A CN 1453284 A CN1453284 A CN 1453284A CN 03126655 CN03126655 CN 03126655 CN 03126655 A CN03126655 A CN 03126655A CN 1453284 A CN1453284 A CN 1453284A
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China
Prior art keywords
synthetic method
solid acid
sucralose
acid catalyst
acetic ester
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CN 03126655
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CN1176094C (en
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王三永
李春荣
李晔
曹敢星
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Guangdong Guangye Qingyi Food Technology Co ltd
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GUANGDONG PROV FOOD INDUSTRY INST
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Priority to CNB03126655XA priority Critical patent/CN1176094C/en
Priority to PCT/CN2003/000655 priority patent/WO2004104016A1/en
Priority to AU2003257786A priority patent/AU2003257786A1/en
Publication of CN1453284A publication Critical patent/CN1453284A/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H13/00—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
    • C07H13/02—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids
    • C07H13/04—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids having the esterifying carboxyl radicals attached to acyclic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00—Processes for the preparation of sugar derivatives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H5/00—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium
    • C07H5/02—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium to halogen

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Saccharide Compounds (AREA)

Abstract

The present invention discloses the synthesis of trichlorosucrose. Sucrose material is mixed with N, N-dimethyl formamide solution, made to produce ester exchange reaction with ethyl acetate in the action of solid sulfate catalyst, which may be adsorbed on polymer carrier, to produce sucrose-6-acetate. Sucrose-6-acetate is then chlorohydrinated to produce trichlorosucrose. The present invention has the advantages of simple technological process, high product purity, low production cost, etc. and is suitable for industrial production.

Description

A kind of Synthetic Method of Sucralose
Affiliated technical field
The present invention relates to a kind of sweetening agent---Synthetic Method of Sucralose.
Background technology
Sucralose, chemical name 4,1 ', 6 '-three chloro-4,1 ', 6 '-three deoxidation sucralose, its structural formula is:
Figure A0312665500031
The sugariness of Sucralose is 600 times of sucrose, is used as sweetening agent by more than 20 state approvals.
The preparation method of Sucralose has single radical protection method and full radical protection method two big classes substantially.Full radical protection method (as U.S. Pat 4801700, US4783526, US4362869 record) complex process does not have suitability for industrialized production to be worth; Usually concerning glucide, it is more more active that the hydroxyl on 6 is gone up hydroxyl than other positions, therefore, want to make other hydroxyls to react, and 6 hydroxyls remains unchanged, and just need carry out radical protection to 6 hydroxyls, and this is single basic starting point of protecting consideration.Therefore the core of single radical protection method is the preparation of cane sugar-6-acetic ester.The structural formula of cane sugar-6-acetic ester is:
Figure A0312665500032
The synthetic method of cane sugar-6-acetic ester mainly contains two kinds: the ethyl acetate method is (as U.S. Pat 4,889,928; 5; 449,772 the record) and the Dibutyltin oxide method (as U.S. Pat 5,023; 329; 4,950,746 records); cane sugar-6-acetic ester and Vilsmeier reagent react obtain sucralose-6-acetic ester, after the deacetylation reaction obtains the product Sucralose.These synthetic methods have certain advance, but also have certain limitation, as complex process, production cost height.
Summary of the invention
The object of the present invention is to provide a kind of new Synthetic Method of Sucralose, this method technology is simple, production cost is low.
A kind of Synthetic Method of Sucralose provided by the invention, it is characterized in that with sucrose being raw material, add N, dinethylformamide solution, at the vitriol solid acid catalyst or be adsorbed under the vitriol solid acid catalyst effect on the polymer carrier and ethyl acetate generation transesterification reaction, generate cane sugar-6-acetic ester, cane sugar-6-acetic ester generates Sucralose through chloro, alcoholysis reaction again.
The present invention is surprised to find, and sucrose molecules and ethyl acetate optionally generate cane sugar-6-acetic ester under some catalyst action, and this selectivity is more than 70%, even can be more than 85%.These catalyzer are actually some solid acid catalysts, also cry Lewies acid on organic chemistry.Industrially sometimes this class solid acid is adsorbed on the polymer carrier, as silica gel.These solid acid catalysts are ferric sulfate, cerous sulfate, zinc chloride, aluminum chloride and zirconium chloride etc.Preferably sulfuric acid cerium of the present invention and be absorbed in cerous sulfate on the silica gel as catalyst for reaction.The cane sugar-6-acetic ester purity that the present invention obtains can directly react with multiple chlorinating agent usually more than 80%, and the preferred Vielsmeier reagent of the present invention generates sucralose-6-acetic ester.The sucralose-6-acetic ester that generates promptly generates Sucralose through alcoholysis reaction again after purifying, alcoholysis reaction is selected sodium methylate/methyl alcohol or sodium ethylate/ethanol system for use.Overall yield of reaction is at (in sucrose) more than 18%.
Compare with existing Synthetic Method of Sucralose, the present invention has advantages such as technology is simple, product purity is high, production cost is low, is fit to very much suitability for industrialized production.
The present invention is further illustrated below in conjunction with embodiment.
Embodiment
1. cane sugar-6-acetic ester is synthetic
In the 1000ml three-necked bottle, add 60g sucrose, 250mlN, dinethylformamide, 100ml ethyl acetate, 1g cerous sulfate-silica gel (1: 1), be heated to 80 ℃ and also under agitation reacted 4 hours, be chilled to 5 ℃, filtering recovering catalyst, the mother liquor normal pressure reclaims ethyl acetate down, reclaim under reduced pressure DMF gets syrup 68g again, and HPLC (joining the differential detector) surveys in the syrup and contains cane sugar-6-acetic ester 83.4%.
2. sucralose-6-acetic ester is synthetic
Get above-mentioned 68g syrup 400mlN, after the dinethylformamide dissolving, be chilled to-20 ℃, drip thionyl chloride 100ml, the control rate of addition maintains the temperature at below 0 ℃ the dropping process, after dropwising, on 0 ℃, stirred 30 minutes again, slowly be warming up to 110 ℃ then, and remain on 110 ℃ of 4 reactions hour down.Reaction solution is chilled to 10 ℃, and stirring down the Dropwise 5 0%NaOH aqueous solution pH value that neutralizes is 7.Remove by filter salinity, mother liquor is evaporated to dried, adds the 300ml water dissolution and divides three extractions, combined ethyl acetate with the 800ml ethyl acetate again, after activated carbon decolorizing is handled, reclaim acetic ester, use the solvent recrystallization secondary again, get sucralose-6-acetic ester 50g, HPLC detects, and content is 96%.
3. Sucralose is synthetic
The 50g sucralose-6-acetic ester is after vacuum-drying, join in the 1000ml three-necked bottle, add the 400ml anhydrous methanol simultaneously, after the heating for dissolving, the methanol solution that adds 1.7ml concentration 27% sodium methylate, reaction is 5 hours under the room temperature, and being neutralized to pH value with weakly acidic resin after reaction finishes is 7, and vacuum steams methyl alcohol, obtain the 42.5g syrup, this syrup is purified through simple, get final product about 39.7g, purity is 99% Sucralose product.

Claims (6)

1, a kind of Synthetic Method of Sucralose, it is characterized in that with sucrose being raw material, add N, dinethylformamide solution, at the vitriol solid acid catalyst or be adsorbed under the vitriol solid acid catalyst effect on the polymer carrier and ethyl acetate generation transesterification reaction, generate cane sugar-6-acetic ester, cane sugar-6-acetic ester generates Sucralose through chloro, alcoholysis reaction again.
2, synthetic method according to claim 1 is characterized in that described vitriol solid acid catalyst is ferric sulfate, cerous sulfate, zinc chloride, aluminum chloride or zirconium chloride.
3, synthetic method according to claim 1 is characterized in that described vitriol solid acid catalyst is a cerous sulfate.
4, synthetic method according to claim 1 is characterized in that the described vitriol solid acid catalyst that is adsorbed on the polymer carrier is cerous sulfate-silica gel.
5, synthetic method according to claim 1 is characterized in that described chlorination selects Vielsmerer reagent for use.
6, synthetic method according to claim 1 is characterized in that described alcoholysis reaction selects sodium methylate/methyl alcohol or sodium ethylate/ethanol system for use.
CNB03126655XA 2003-05-23 2003-05-23 Synthesis of trichlorosucrose Expired - Lifetime CN1176094C (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
CNB03126655XA CN1176094C (en) 2003-05-23 2003-05-23 Synthesis of trichlorosucrose
PCT/CN2003/000655 WO2004104016A1 (en) 2003-05-23 2003-08-11 Process for the preparation of 4, 1', 6'-trichloro-4, 1', 6'­trideoxygalactosucrose
AU2003257786A AU2003257786A1 (en) 2003-05-23 2003-08-11 Process for the preparation of 4, 1', 6'-trichloro-4, 1', 6'-trideoxygalactosucrose

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Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1312164C (en) * 2003-09-23 2007-04-25 李宝才 Method for synthesizing sucralose by monoester method
CN100418976C (en) * 2006-04-03 2008-09-17 广州科宏食品添加物有限公司 Process for preparing sucralose
CN100567319C (en) * 2006-07-12 2009-12-09 上海迪赛诺维生素有限公司 A kind of crystallization method of Sucralose
CN1814609B (en) * 2006-03-06 2010-11-10 盐城捷康三氯蔗糖制造有限公司 Method for improving trichloro galacto sucrose synthetic yield
CN102002078A (en) * 2010-11-17 2011-04-06 广西工学院 Method for continuously preparing sucrose-6-acetic ester
CN101029062B (en) * 2007-04-09 2011-06-15 淄博联技甜味剂有限公司 Synthesis of trichloio-sugar
CN102639550A (en) * 2009-10-12 2012-08-15 塔特和莱利技术有限公司 Low temperature, single solvent process for the production of sucrose-6-ester
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
CN104098617A (en) * 2013-04-08 2014-10-15 南京工业大学 Preparation method of sucrose-6-acetate
CN104387427A (en) * 2014-10-30 2015-03-04 安徽金禾实业股份有限公司 Method for producing sucralose
CN105646602A (en) * 2016-03-04 2016-06-08 李云军 Deacylating method of sucralose-6-acetate
CN105707832A (en) * 2016-03-07 2016-06-29 李云军 Sucralose sweetening agent
CN105859802A (en) * 2016-05-14 2016-08-17 广西科技大学 Sucralose crystallization and purification method
CN108997259A (en) * 2018-08-31 2018-12-14 山东亚邦化工科技有限公司 The technique and device decolourized for synthetic sweetener acesulfame potassium or mother liquor of sucralose
CN112574258A (en) * 2020-12-02 2021-03-30 安徽金禾实业股份有限公司 Method for controlling sucralose acidity

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100420697C (en) 2006-08-30 2008-09-24 河北苏科瑞科技有限公司 Method of preparing trichloro sucrose-6-organic acid ester
US8258291B2 (en) 2006-10-25 2012-09-04 Mamtek International Limited Process for the preparation of sucralose by the chlorination of sugar with triphosgene (BTC)
US20080103295A1 (en) * 2006-10-25 2008-05-01 David Losan Ho Process for the preparation of sucrose-6-ester by esterification in the presence of solid superacid catalyst
CN105985386B (en) * 2015-02-11 2018-06-26 大连民族学院 A kind of sucrose ester type cationic gene carriers and preparation method thereof

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DE3165986D1 (en) * 1980-07-08 1984-10-18 Tate & Lyle Plc Process for the preparation of 4, 1',6'-trichloro-4,1',6'-trideoxygalactosucrose (tgs)
GB8525953D0 (en) * 1985-10-21 1985-11-27 Mcneilab Inc Preparation of galactopyranoside
GB8622345D0 (en) * 1986-09-17 1986-10-22 Tate & Lyle Plc Sucrose derivatives
US4950746A (en) * 1988-07-18 1990-08-21 Noramco, Inc. Process for synthesizing sucrose derivatives by regioselective reaction
US4980463A (en) * 1989-07-18 1990-12-25 Noramco, Inc. Sucrose-6-ester chlorination
US5023329A (en) * 1990-04-23 1991-06-11 Noramco, Inc. Sucrose-6-ester production process
US5449772A (en) * 1991-05-21 1995-09-12 Tate & Lyle Public Ltd. Co. Continuous process for the preparation of sucrose 6-esters

Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1312164C (en) * 2003-09-23 2007-04-25 李宝才 Method for synthesizing sucralose by monoester method
CN1814609B (en) * 2006-03-06 2010-11-10 盐城捷康三氯蔗糖制造有限公司 Method for improving trichloro galacto sucrose synthetic yield
US7884203B2 (en) 2006-03-06 2011-02-08 Jk Sucralose Inc. Method of sucralose synthesis yield
CN100418976C (en) * 2006-04-03 2008-09-17 广州科宏食品添加物有限公司 Process for preparing sucralose
CN100567319C (en) * 2006-07-12 2009-12-09 上海迪赛诺维生素有限公司 A kind of crystallization method of Sucralose
CN101029062B (en) * 2007-04-09 2011-06-15 淄博联技甜味剂有限公司 Synthesis of trichloio-sugar
CN102639550A (en) * 2009-10-12 2012-08-15 塔特和莱利技术有限公司 Low temperature, single solvent process for the production of sucrose-6-ester
CN102639550B (en) * 2009-10-12 2016-01-27 塔特和莱利技术有限公司 For the production of low temperature, the single solvent method of sucrose-6-ester
CN102002078A (en) * 2010-11-17 2011-04-06 广西工学院 Method for continuously preparing sucrose-6-acetic ester
CN102002078B (en) * 2010-11-17 2012-05-30 广西工学院 Method for continuously preparing sucrose-6-acetic ester
CN102816188B (en) * 2012-08-13 2015-05-13 南通市常海食品添加剂有限公司 Production technology of sucralose
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
CN104098617A (en) * 2013-04-08 2014-10-15 南京工业大学 Preparation method of sucrose-6-acetate
CN104387427A (en) * 2014-10-30 2015-03-04 安徽金禾实业股份有限公司 Method for producing sucralose
CN105646602A (en) * 2016-03-04 2016-06-08 李云军 Deacylating method of sucralose-6-acetate
CN105707832A (en) * 2016-03-07 2016-06-29 李云军 Sucralose sweetening agent
CN105859802A (en) * 2016-05-14 2016-08-17 广西科技大学 Sucralose crystallization and purification method
CN105859802B (en) * 2016-05-14 2019-02-12 广西科技大学 A kind of crystallization of Sucralose and purification process
CN108997259A (en) * 2018-08-31 2018-12-14 山东亚邦化工科技有限公司 The technique and device decolourized for synthetic sweetener acesulfame potassium or mother liquor of sucralose
CN112574258A (en) * 2020-12-02 2021-03-30 安徽金禾实业股份有限公司 Method for controlling sucralose acidity

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AU2003257786A1 (en) 2004-12-13
CN1176094C (en) 2004-11-17

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