CN101367849B - Preparation method for sucrose trichloride -2,3,6,3',4'-pentaacetate - Google Patents
Preparation method for sucrose trichloride -2,3,6,3',4'-pentaacetate Download PDFInfo
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- CN101367849B CN101367849B CN2007100261035A CN200710026103A CN101367849B CN 101367849 B CN101367849 B CN 101367849B CN 2007100261035 A CN2007100261035 A CN 2007100261035A CN 200710026103 A CN200710026103 A CN 200710026103A CN 101367849 B CN101367849 B CN 101367849B
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Abstract
The present invention relates to a method for preparing sucralose-2, 3, 6, 3', 4'-pentaacetate. Sucrose-2, 3, 6, 3', 4'-pentaacetate is added into solvent containing tertiary amine, and after the temperature is decreased to 0 DEG C, thionyl chloride is dripped in; then, after being increased to 110 DEG C to 115 DEG C, the temperature is kept for two to six hours; after sufficient reaction, the temperature is reduced to the room temperature; caustic soda liquid is used to carry out neutralization; ethyl acetate is used to carry out extraction and condensation; water is added into the extract and heated until the extract is resolved; and sucralose-2, 3, 6, 3', 4'-pentaacetate crystals are precipitated by cooling. Compared with the prior art, the technical scheme of the method has the advantages of mild reaction conditions and easy control, and both the yield and purity of the product are higher than the optimal values of the prior art.
Description
Technical field
The present invention relates to sweetening agent " TGS ", relate in particular to the preparation method of the key intermediate " TGS-2,3,6,3 ', 4 '-pentaacetate " of this sweetening agent, belong to the fine chemical technology field.
Background technology
TGS is a kind of functional type sweeting agent, and it has represented the last word of sweeting agent development to a certain extent, sees from molecular structure, and it is that 4,1 ', 6 ' three hydroxyls are formed by three chlorine atoms replacements in the sucrose molecules.And 8 hydroxyls are arranged in the sucrose molecules, and be respectively three primary carbon hydroxyls (6,1 ', 6 ') and five secondary carbon hydroxyls (2,3,4,3 ', 4 '), prepare TGS; A kind of method is through 6-position hydroxyl in the protection sucrose molecules, carries out selective chlorination then, because 1 ', 6 '-hydroxyl is a primary hydroxyl; More active relatively; Chlorination reaction is prone to carry out, and 4-position hydroxyl is a secondary hydroxyl, and its activity and other four secondary hydroxyls are approaching; Selectivity is relatively poor, thereby causes shortcomings such as chlorination reaction poor selectivity, yield are low, the difficult separation of product; Another kind method be through selective protection sucrose 2,3,3 ', 4 ', five hydroxyls of 6-; Remaining 4,1 ', 6 ' three hydroxyls of chlorination then; As far as chlorination reaction; This method is remaining three hydroxyls in the chlorinated sucrose molecule, and selectivity is single, and the purity of yield and intermediate product is higher.
TGS-2,3,6,3 '; 4 '-pentaacetate preparation method has bibliographical information, as: 0 ' Brien etc. have disclosed a kind of TGS-2,3 in US4783526; 6, the preparation method of 3 ', 4 '-pentaacetate, promptly sulfur oxychloride carries out the chlorating method in the system of triphenylphosphinc oxide and toluene composition; Raw materials used triphenylphosphinc oxide of this method and solvent toluene can remain in the finished product, and health is worked the mischief, and the single step yield is 75%; Tully etc. in US4801700, disclose a kind of with sulfur oxychloride in triphenylphosphinc oxide and 1, the system that the 2-ethylene dichloride is formed is carried out the chlorating method, this method is still used triphenylphosphinc oxide, the single step yield is 66%.
Take a broad view of above method, the problem of existence: 1, the raw material triphenylphosphine oxide costs an arm and a leg, and does not meet needs of production; 2, triphenylphosphine oxide toxicity is big, can remain in the finished product, thereby the postprocessing working procedures of increase finished product increases production cost.
Summary of the invention
The object of the present invention is to provide TGS-2,3,6,3 '; A kind of preparation method of 4 '-pentaacetate is intended to overcome all deficiencies of prior art, makes TGS-2,3; 6, the preparation process of 3 ', 4 '-pentaacetate more is prone to carry out, and product more is prone to purify, yield is higher.
The object of the invention is realized through following technical scheme:
TGS-2,3,6, the preparation method of 3 ', 4 '-pentaacetate is with sucrose-2; 3,6,3 ', 4 '-pentaacetate is the main reaction raw material, generates TGS-2 through chlorination reaction; 3,6,3 ', 4 '-pentaacetate is characterized in that: may further comprise the steps in regular turn---
1. with sucrose-2,3,6,3 ', 4 '-pentaacetate adds in the middle of the tertiary amine solvent;
2. solution is cooled to-30～0 ℃, is added dropwise to chlorizating agent;
3. after dropwising, be warming up to 105～120 ℃;
4. be incubated 2～6 hours, it is fully reacted;
5. be cooled to room temperature, transfer to neutrality, then with ethyl acetate extraction, concentrated with liquid caustic soda;
6. the further water heating for dissolving of extract that obtains, the cooling post crystallization is separated out TGS-2,3,6,3 ', 4 '-pentaacetate crystal.
Further, above-mentioned TGS-2,3,6, the preparation method of 3 ', 4 '-pentaacetate, wherein, the quality consumption of the tertiary amine solvent of step in 1. is a sucrose-2,3,6, the 3-10 of 3 ', 4 '-pentaacetate is doubly.
Again further, above-mentioned TGS-2,3,6, the preparation method of 3 ', 4 '-pentaacetate, wherein, the step 2. mole dosage of middle chlorizating agent is a sucrose-2,3,6, the 4-7 of 3 ', 4 '-pentaacetate is doubly.
Again further, above-mentioned TGS-2,3,6, the preparation method of 3 ', 4 '-pentaacetate, wherein, the tertiary amine solvent preferred N of step in 1., dinethylformamide.
Further, above-mentioned TGS-2,3,6, the preparation method of 3 ', 4 '-pentaacetate, wherein, the chlorizating agent preferred sulfur oxychloride of step in 2..
The present invention has following outstanding advantage:
(1) do not use triphenylphosphine oxide as raw material or contain the solvent of phenyl ring;
(2) reaction process mild condition, easy to control;
(3) confirmed the product crystallization condition, that is: water has been joined in the last viscous material to heat up and make its dissolving, cooling, crystallization again, pilot product purity reaches more than 98%, and reaction yield surpasses 82%.
Embodiment
Be several the specific exampless of using technical scheme of the present invention below, they only provide as an example, are not regarded as application limitations of the present invention.All operational conditions be equal to replacement, all drop within protection scope of the present invention.
Embodiment 1:
A 1000ml four-hole round-bottomed flask is equipped with mechanical stirring, TM and prolong, adds to contain 100g (0.18mol) sucrose-2,3; 6, the 700ml DMF (N of 3 ', 4 '-pentaacetate; Dinethylformamide) solution is cooled to-10～0 ℃, is added dropwise to 100g (0.84mol) sulfur oxychloride; Dropwise and be incubated half a hour, in 1 hour, slowly be warming up to 110-115 ℃ then, insulation reaction 3 hours; Reaction finishes, and is chilled to room temperature, regulates PH to neutral with liquid caustic soda, extracts respectively three times with 200ml ETHYLE ACETATE again; Activated carbon decolorizing concentrates and removes ETHYLE ACETATE, adds 150ml water, and the heating for dissolving postcooling is separated out crystal; Suction filtration, dry 91.6g TGS-2,3,6,3 '; 4 '-pentaacetate crystal, purity are 98.5% (HPLC), yield 83.4%.
Embodiment 2:
A 1000ml four-hole round-bottomed flask is equipped with mechanical stirring, TM and prolong, adds to contain 100g (0.18mol) sucrose-2; 3,6,3 '; The 700ml DMF solution of 4 '-pentaacetate is cooled to-20～-10 ℃, is added dropwise to 110g (0.92mol) sulfur oxychloride; Dropwise and be incubated half a hour, in 1 hour, slowly be warming up to 110-115 ℃ then, insulation reaction 4 hours; Reaction finishes, and is chilled to room temperature, regulates PH to neutral with liquid caustic soda, extracts respectively three times with 200ml ETHYLE ACETATE again; Activated carbon decolorizing concentrates and removes ETHYLE ACETATE, adds 150ml water, and the heating for dissolving postcooling is separated out crystal; Suction filtration, dry 85.5g TGS-2,3,6,3 '; 4 '-pentaacetate crystal, purity are 98.0% (HPLC), yield 77.8%.
Embodiment 3:
A 1000ml four-hole round-bottomed flask is equipped with mechanical stirring, TM and prolong, adds to contain 100g (0.18mol) sucrose-2; 3,6,3 '; The 700ml DMF solution of 4 '-pentaacetate is cooled to-25～-15 ℃, is added dropwise to 90g (0.75mol) sulfur oxychloride; Dropwise and be incubated half a hour, in 1 hour, slowly be warming up to 110-115 ℃ then, insulation reaction 2 hours; Reaction finishes, and is chilled to room temperature, regulates PH to neutral with liquid caustic soda, extracts respectively three times with 200ml ETHYLE ACETATE again; Activated carbon decolorizing concentrates and removes ETHYLE ACETATE, adds 150ml water, and the heating for dissolving postcooling is separated out crystal; Suction filtration, dry 82.6g TGS-2,3,6,3 '; 4 '-pentaacetate crystal, purity are 97.6% (HPLC), yield 75.1%.
Embodiment 4:
A 1000ml four-hole round-bottomed flask is equipped with mechanical stirring, TM and prolong, adds to contain 100g (0.18mol) sucrose-2; 3,6,3 '; The 700ml DMF solution of 4 '-pentaacetate is cooled to-15～-5 ℃, is added dropwise to 100g (0.84mol) sulfur oxychloride; Dropwise and be incubated half a hour, in 1 hour, slowly be warming up to 105-110 ℃ then, insulation reaction 5 hours; Reaction finishes, and is chilled to room temperature, regulates PH to neutral with liquid caustic soda, extracts respectively three times with 200ml ETHYLE ACETATE again; Activated carbon decolorizing concentrates and removes ETHYLE ACETATE, adds 150ml water, and the heating for dissolving postcooling is separated out crystal; Suction filtration, dry 68.6g TGS-2,3,6,3 '; 4 '-pentaacetate crystal, purity are 98.0% (HPLC), yield 62.4%.
Embodiment 5:
In the 1000ml four-hole round-bottomed flask that is equipped with mechanical stirring, TM and prolong, add and contain 100g (0.18mol) sucrose-2,3; 6, the 700ml DMF solution of 3 ', 4 '-pentaacetate; Be cooled to-30～-20 ℃, be added dropwise to 100g (0.84mol) sulfur oxychloride, dropwise and be incubated half a hour; In 1 hour, slowly be warming up to 115-120 ℃ then, insulation reaction 6 hours; Reaction finishes, and is chilled to room temperature, regulates PH to neutral with liquid caustic soda, extracts respectively three times with 200ml ETHYLE ACETATE again; Activated carbon decolorizing concentrates and removes ETHYLE ACETATE, adds 150ml water, and the heating for dissolving postcooling is separated out crystal; Suction filtration, dry 72.5g TGS-2,3,6,3 '; 4 '-pentaacetate crystal, purity are 97.5% (HPLC), yield 66.0%.
Embodiment 6:
In the 100L enamel reaction still that is equipped with mechanical stirring, TM and condensing surface, add and contain 10Kg (18mol) sucrose-2,3; 6, the 70Kg DMF solution of 3 ', 4 '-pentaacetate; Be cooled to-10～0 ℃, be added dropwise to 10Kg (84mol) sulfur oxychloride, dropwise and be incubated half a hour; In 1 hour, slowly be warming up to 110-115 ℃ then, insulation reaction 3 hours; Reaction finishes, and is chilled to room temperature, regulates PH to neutral with liquid caustic soda, extracts respectively three times with 20L ETHYLE ACETATE again; Activated carbon decolorizing concentrate to be removed ETHYLE ACETATE, concentrates residuum with hot water dissolving, crystallisation by cooling, get rid of filter, dry 90.8Kg TGS-2; 3,6,3 '; 4 '-pentaacetate crystal, purity are 98.0% (HPLC), yield 82.6%.
Claims (4)
1. TGS-2,3,6, the preparation method of 3 ', 4 '-pentaacetate is with sucrose-2; 3,6,3 ', 4 '-pentaacetate is the main reaction raw material, generates TGS-2 through chlorination reaction; 3,6,3 ', 4 '-pentaacetate is characterized in that: may further comprise the steps in regular turn---
1. with sucrose-2,3,6,3 ', 4 '-pentaacetate adds N, in the middle of the dinethylformamide solvent;
2. solution is cooled to-30～0 ℃, is added dropwise to chlorizating agent;
3. after dropwising, be warming up to 105～120 ℃;
4. be incubated 2～6 hours, it is fully reacted;
5. be cooled to room temperature, transfer to neutrality, then with ethyl acetate extraction, concentrated with liquid caustic soda;
6. the further water heating for dissolving of extract that obtains, the cooling post crystallization is separated out TGS-2,3,6,3 ', 4 '-pentaacetate crystal.
2. TGS-2,3,6 according to claim 1, the preparation method of 3 ', 4 '-pentaacetate is characterized in that: the N of step in 1., the quality consumption of dinethylformamide is a sucrose-2,3,6, the 3-10 of 3 ', 4 '-pentaacetate is doubly.
3. TGS-2,3,6 according to claim 1, the preparation method of 3 ', 4 '-pentaacetate is characterized in that: the step 2. mole dosage of middle chlorizating agent is a sucrose-2,3,6, the 4-7 of 3 ', 4 '-pentaacetate is doubly.
4. TGS-2,3,6 according to claim 1, the preparation method of 3 ', 4 '-pentaacetate is characterized in that: the chlorizating agent of step in 2. is sulfur oxychloride.
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| CN2007100261035A CN101367849B (en) | 2007-08-15 | 2007-08-15 | Preparation method for sucrose trichloride -2,3,6,3',4'-pentaacetate |
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| CN2007100261035A CN101367849B (en) | 2007-08-15 | 2007-08-15 | Preparation method for sucrose trichloride -2,3,6,3',4'-pentaacetate |
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| CN101367849B true CN101367849B (en) | 2012-03-21 |
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| CN1800194A (en) * | 2006-01-12 | 2006-07-12 | 上海迪赛诺维生素有限公司 | Sucralose synthesis method |
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| CN1800194A (en) * | 2006-01-12 | 2006-07-12 | 上海迪赛诺维生素有限公司 | Sucralose synthesis method |
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