CN103145772A - Preparation method of sucralose - Google Patents
Preparation method of sucralose Download PDFInfo
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- CN103145772A CN103145772A CN2013100986675A CN201310098667A CN103145772A CN 103145772 A CN103145772 A CN 103145772A CN 2013100986675 A CN2013100986675 A CN 2013100986675A CN 201310098667 A CN201310098667 A CN 201310098667A CN 103145772 A CN103145772 A CN 103145772A
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Abstract
The invention relates to sucralose, and in particular relates to a preparation method of sucralose. The preparation method comprises the following steps of: dissolving sucrose and reacting with an esterifying reagent to prepare sucrose-6-ester; performing sectional chlorination on sucrose-6-ester by using chlorine to prepare sucralose-6-ester; and finally, deprotecting sucralose-6-ester by using strong base to obtain sucralose. The method is easy to operate, short in process procedures, mild in reaction conditions, low in cost and low in energy consumption, and has wide development and application prospects.
Description
Technical field
The present invention relates to Sucralose, be specifically related to a kind of preparation method of Sucralose.
Background technology
Sucralose (TGS) is by (the Tate﹠amp of Britain Tai Lai company; Lyie) with the common a kind of novel sweetener developing and applied for a patent in 1976 in London University.Be unique functional sweetener take sucrose as raw material, original trade(brand)name is Splenda, and sugariness can reach 600 times of sucrose.
US 4362869 discloses triphenylmethyl chloride and has become ether to protect three primary hydroxyls with hydroxyl reaction, then is reacted into ester with aceticanhydride, five hydroxyls of protection residue, in pyridine solution, under-75 ℃ through the thionyl chloride chloro.The shortcoming of this technique is severe reaction conditions, and synthesis step is many, and complex process is not suitable for suitability for industrialized production.
US 4380476 discloses aceticanhydride and sucrose has been carried out monoacylated, through the post resin isolation, makes chlorinating agent with the Vilsmeier reagent of phosphorus pentachloride and N'N-dimethyl formamide reaction preparation.But this technique overall yield is obviously on the low side, and the post lock out operation is too loaded down with trivial details, is difficult to realize industrialization.
EP 0356304 discloses preparation 6-benzoyl sucrose under the catalysis of azoformic acid isopropyl ester, and total recovery is higher.But the large usage quantity of azoformic acid isopropyl ester in this technique, price is higher, is unfavorable for reducing costs.
In sum, the preparation technology of Sucralose has a lot of shortcomings also to be subject to being permitted multifactorial restriction at present, makes the preparation method of Sucralose need improvement badly.
Summary of the invention
The preparation method who the purpose of this invention is to provide a kind of simple to operate, mild condition, the Sucralose that with low cost, technical process is short, energy consumption is low.
The preparation method of Sucralose of the present invention comprises the following steps:
(1) with sucrose dissolved and esterifying reagent reaction, preparation sucrose-6-ester;
(2) adopt chlorine to carry out the segmentation chlorination reaction to sucrose-6-ester, the preparation sucralose-6-ester;
(3) sucralose-6-ester highly basic deprotection gets Sucralose.
The solvent of the described dissolving saccharose of step (1) is organic solvent, at least a in DMF, N,N-dimethylacetamide or ethyl acetate.When by two or more solvent composition, can mix by arbitrary proportion between them, consider suitability for industrialized production cheaply, preferred DMF.
The described esterifying reagent of step (1) is methyl-chloroformate, Vinyl chloroformate, a kind of in the chloroformic acid tert-butyl ester, chloroformic acid benzyl ester or phenyl chloroformate.
The mol ratio of the described sucrose of step (1) and esterifying reagent is 1:2～8.
In step (2), the segmentation chlorination reaction is carried out according to following steps:
First paragraph: sucrose-6-ester is cooled to-20～-15 ℃, passes into chlorine 7～10h;
Second segment: be warming up to-10～-5 ℃, pass into chlorine 4～7h;
The 3rd section: be warming up to 5～20 ℃, pass into chlorine 1～3h.
The described highly basic deprotecting regent of step (3) is a kind of in sodium methylate, sodium ethylate, magnesium methylate or magnesium ethylate, and the mol ratio of highly basic deprotecting regent and sucralose-6-ester is 1:1.
Reaction equation is:
Beneficial effect of the present invention is as follows:
The present invention is simple to operate, technical process is short, reaction conditions is gentle, with low cost, energy consumption is low, has wide development and application prospect.
Embodiment
Below in conjunction with embodiment, the present invention is described further.
Embodiment 1
400kg sucrose adds 800kgN, dissolves in dinethylformamide, adds the 884kg methyl-chloroformate below 5 ℃, and insulation is finished, and the underpressure distillation DMF is steamed, gets sucrose-6-ester, and is standby.
Sucrose-6-ester is cooled to-20 ℃, passes into chlorine, passes into chlorine 10h, slowly is warming up to-10 ℃, continue logical chlorine 7h, logical finishing slowly is warming up to 5 ℃, logical chlorine 3h, logical finishing is cooled to 0 ℃ and adds ammoniacal liquor, regulates pH=7, underpressure distillation, steamed, decolouring, filter ethyl acetate extraction, distillation ethyl acetate, add entry, crystallization obtains crude product.Crude product is refining with ethyl acetate, and crystal's system gets the 200kg sucralose-6-ester.
Sucralose-6-ester adds 600kg methyl alcohol and 24kg sodium methylate, and room temperature reaction reacts complete, adds resin cation (R.C.), distillating carbinol, and the steamed water decolorization that adds is distilled to crystallization, and the cooling crystallization gets the 157kg Sucralose.
Embodiment 2
400kg sucrose adds 850kgN, dissolves in the N-N,N-DIMETHYLACETAMIDE, adds the 884kg methyl-chloroformate below 5 ℃, and insulation is finished, and the underpressure distillation N,N-dimethylacetamide is steamed, gets sucrose-6-ester, and is standby.
Sucrose-6-ester is cooled to-20 ℃, passes into chlorine, passes into chlorine 10h, slowly is warming up to-10 ℃, continue logical chlorine 7h, logical finishing slowly is warming up to 5 ℃, logical chlorine 3h, logical finishing is cooled to 0 ℃ and adds ammoniacal liquor, regulates pH=7, underpressure distillation, steamed, decolouring, filter ethyl acetate extraction, distillation ethyl acetate, add entry, crystallization obtains crude product.Crude product is refining with ethyl acetate, and crystal's system gets the 201kg sucralose-6-ester.
Sucralose-6-ester adds 600kg methyl alcohol and 24kg sodium methylate, and room temperature reaction reacts complete, adds resin cation (R.C.), distillating carbinol, and the steamed water decolorization that adds is distilled to crystallization, and the cooling crystallization gets the 156kg Sucralose.
Embodiment 3
400kg sucrose adds 800kgN, dissolves in dinethylformamide, adds the 252kg Vinyl chloroformate below 5 ℃, and insulation is finished, and the underpressure distillation DMF is steamed, gets sucrose-6-ester, and is standby.
Sucrose-6-ester is cooled to-20 ℃, passes into chlorine, passes into chlorine 10h, slowly is warming up to-10 ℃, continue logical chlorine 7h, logical finishing slowly is warming up to 5 ℃, logical chlorine 3h, logical finishing is cooled to 0 ℃ and adds ammoniacal liquor, regulates pH=7, underpressure distillation, steamed, decolouring, filter ethyl acetate extraction, distillation ethyl acetate, add entry, crystallization obtains crude product.Crude product is refining with ethyl acetate, and crystal's system gets the 183kg sucralose-6-ester.
Sucralose-6-ester adds 549kg methyl alcohol and 27kg sodium ethylate, and room temperature reaction reacts complete, adds resin cation (R.C.), distillating carbinol, and the steamed water decolorization that adds is distilled to crystallization, and the cooling crystallization gets the 140kg Sucralose.
Embodiment 4
400kg sucrose adds 800kgN, dissolves in dinethylformamide, adds the 884kg methyl-chloroformate below 5 ℃, and insulation is finished, and the underpressure distillation DMF is steamed, gets sucrose-6-ester, and is standby.
Sucrose-6-ester is cooled to-15 ℃, passes into chlorine, passes into chlorine 7h, slowly is warming up to-5 ℃, continue logical chlorine 4h, logical finishing slowly is warming up to 20 ℃, logical chlorine 1h, logical finishing is cooled to 0 ℃ and adds ammoniacal liquor, regulates pH=7, underpressure distillation, steamed, decolouring, filter ethyl acetate extraction, distillation ethyl acetate, add entry, crystallization obtains crude product.Crude product is refining with ethyl acetate, and crystal's system gets the 196kg sucralose-6-ester.
Sucralose-6-ester adds 588kg methyl alcohol and 23kg sodium methylate, and room temperature reaction reacts complete, adds resin cation (R.C.), distillating carbinol, and the steamed water decolorization that adds is distilled to crystallization, and the cooling crystallization gets the 154kg Sucralose.
Embodiment 5
400kg sucrose adds 800kgN, dissolves in dinethylformamide, adds the 252kg Vinyl chloroformate below 5 ℃, and insulation is finished, and the underpressure distillation DMF is steamed, gets sucrose-6-ester, and is standby.
Sucrose-6-ester is cooled to-15 ℃, passes into chlorine, passes into chlorine 7h, slowly is warming up to-5 ℃, continue logical chlorine 4h, logical finishing slowly is warming up to 20 ℃, logical chlorine 1h, logical finishing is cooled to 0 ℃ and adds ammoniacal liquor, regulates pH=7, underpressure distillation, steamed, decolouring, filter ethyl acetate extraction, distillation ethyl acetate, add entry, crystallization obtains crude product.Crude product is refining with ethyl acetate, and crystal's system gets the 180kg sucralose-6-ester.
Sucralose-6-ester adds 540kg methyl alcohol and 26kg sodium ethylate, and room temperature reaction reacts complete, adds resin cation (R.C.), distillating carbinol, and the steamed water decolorization that adds is distilled to crystallization, and the cooling crystallization gets the 138kg Sucralose.
Embodiment 6
400kg sucrose adds 800kgN, dissolves in dinethylformamide, adds the 365kg Vinyl chloroformate below 5 ℃, and insulation is finished, and the underpressure distillation DMF is steamed, gets sucrose-6-ester, and is standby.
Sucrose-6-ester is cooled to-15 ℃, passes into chlorine, passes into chlorine 7h, slowly is warming up to-5 ℃, continue logical chlorine 4h, logical finishing slowly is warming up to 20 ℃, logical chlorine 1h, logical finishing is cooled to 0 ℃ and adds ammoniacal liquor, regulates pH=7, underpressure distillation, steamed, decolouring, filter ethyl acetate extraction, distillation ethyl acetate, add entry, crystallization obtains crude product.Crude product is refining with ethyl acetate, and crystal's system gets the 198kg sucralose-6-ester.
Sucralose-6-ester adds 540kg methyl alcohol and 26kg sodium ethylate, and room temperature reaction reacts complete, adds resin cation (R.C.), distillating carbinol, and the steamed water decolorization that adds is distilled to crystallization, and the cooling crystallization gets the 138kg Sucralose.
Embodiment 7
Synthesizing with embodiment 1 of sucralose-6-ester.
Sucralose-6-ester adds 600kg methyl alcohol and 38kg magnesium methylate, and room temperature reaction reacts complete, adds resin cation (R.C.), distillating carbinol, and the steamed water decolorization that adds is distilled to crystallization, and the cooling crystallization gets the 156kg Sucralose.
Embodiment 8
Synthesizing with embodiment 3 of sucralose-6-ester.
Sucralose-6-ester adds 549kg methyl alcohol and 45kg sodium ethylate, and room temperature reaction reacts complete, adds resin cation (R.C.), distillating carbinol, and the steamed water decolorization that adds is distilled to crystallization, and the cooling crystallization gets the 138kg Sucralose.
Claims (7)
1. the preparation method of a Sucralose, is characterized in that, comprises the following steps:
(1) with sucrose dissolved and esterifying reagent reaction, preparation sucrose-6-ester;
(2) adopt chlorine to carry out the segmentation chlorination reaction to sucrose-6-ester, the preparation sucralose-6-ester;
(3) sucralose-6-ester highly basic deprotection gets Sucralose.
2. the preparation method of Sucralose according to claim 1 is characterized in that: in step (1), the solvent of dissolving saccharose is organic solvent, at least a in DMF, N,N-dimethylacetamide or ethyl acetate.
3. the preparation method of Sucralose according to claim 1 is characterized in that: in step (1), esterifying reagent is methyl-chloroformate, Vinyl chloroformate, a kind of in the chloroformic acid tert-butyl ester, chloroformic acid benzyl ester or phenyl chloroformate.
4. the preparation method of according to claim 1 or 3 described Sucraloses is characterized in that: in step (1), the mol ratio of sucrose and esterifying reagent is 1:2～8.
5. the preparation method of Sucralose according to claim 1 is characterized in that: in step (2), the segmentation chlorination reaction is carried out according to following steps:
First paragraph: sucrose-6-ester is cooled to-20～-15 ℃, passes into chlorine 7～10h;
Second segment: be warming up to-10～-5 ℃, pass into chlorine 4～7h;
The 3rd section: be warming up to 5～20 ℃, pass into chlorine 1～3h.
6. the preparation method of Sucralose according to claim 1 is characterized in that: in step (3), the highly basic deprotecting regent is a kind of in sodium methylate, sodium ethylate, magnesium methylate or magnesium ethylate.
7. the preparation method of according to claim 1 or 6 described Sucraloses is characterized in that: in step (3), the mol ratio of highly basic deprotecting regent and sucralose-6-ester is 1:1.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2013100986675A CN103145772A (en) | 2013-03-26 | 2013-03-26 | Preparation method of sucralose |
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| CN2013100986675A CN103145772A (en) | 2013-03-26 | 2013-03-26 | Preparation method of sucralose |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103965266A (en) * | 2014-04-22 | 2014-08-06 | 南通市常海食品添加剂有限公司 | Chlorination dripping control method for preparation of sucralose |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4980463A (en) * | 1989-07-18 | 1990-12-25 | Noramco, Inc. | Sucrose-6-ester chlorination |
| CN1526716A (en) * | 2003-09-23 | 2004-09-08 | 李宝才 | Method for synthesizing sucralose by using monoester method |
| CN1660868A (en) * | 2004-12-22 | 2005-08-31 | 东南大学 | Method for preparing-ester by using solid chlorine substitution of phosgene |
| US20060205936A1 (en) * | 2005-03-14 | 2006-09-14 | Sl Laboratories, Llc | Chlorination of Sucrose-6-esters |
| CN101121736A (en) * | 2007-09-05 | 2008-02-13 | 江苏天禾药物研究所有限公司 | Method of preparing sucralose |
| CN101139372A (en) * | 2007-10-23 | 2008-03-12 | 南通迈特生物工程有限公司 | Modified sucrose-6-ester chloridization process |
| WO2012071385A1 (en) * | 2010-11-23 | 2012-05-31 | Lexington Pharmaceutical Laboratories, Llc | Low temperature chlorination of carbohydrates |
-
2013
- 2013-03-26 CN CN2013100986675A patent/CN103145772A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4980463A (en) * | 1989-07-18 | 1990-12-25 | Noramco, Inc. | Sucrose-6-ester chlorination |
| CN1526716A (en) * | 2003-09-23 | 2004-09-08 | 李宝才 | Method for synthesizing sucralose by using monoester method |
| CN1660868A (en) * | 2004-12-22 | 2005-08-31 | 东南大学 | Method for preparing-ester by using solid chlorine substitution of phosgene |
| US20060205936A1 (en) * | 2005-03-14 | 2006-09-14 | Sl Laboratories, Llc | Chlorination of Sucrose-6-esters |
| CN101121736A (en) * | 2007-09-05 | 2008-02-13 | 江苏天禾药物研究所有限公司 | Method of preparing sucralose |
| CN101139372A (en) * | 2007-10-23 | 2008-03-12 | 南通迈特生物工程有限公司 | Modified sucrose-6-ester chloridization process |
| WO2012071385A1 (en) * | 2010-11-23 | 2012-05-31 | Lexington Pharmaceutical Laboratories, Llc | Low temperature chlorination of carbohydrates |
Non-Patent Citations (1)
| Title |
|---|
| 鲁道夫•博克: "《分析化学中试样分解方法手册》", 31 March 1987, 中国标准出版社 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103965266A (en) * | 2014-04-22 | 2014-08-06 | 南通市常海食品添加剂有限公司 | Chlorination dripping control method for preparation of sucralose |
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Application publication date: 20130612 |