CN102417527A - Method for synthesizing sucralose-6-ethyl ester - Google Patents
Method for synthesizing sucralose-6-ethyl ester Download PDFInfo
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- CN102417527A CN102417527A CN2011103403123A CN201110340312A CN102417527A CN 102417527 A CN102417527 A CN 102417527A CN 2011103403123 A CN2011103403123 A CN 2011103403123A CN 201110340312 A CN201110340312 A CN 201110340312A CN 102417527 A CN102417527 A CN 102417527A
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- 0 OC(C(CCl)OC1(CCl)OC(*C(CCl)C([C@@]2O)Cl)C2O)C1O Chemical compound OC(C(CCl)OC1(CCl)OC(*C(CCl)C([C@@]2O)Cl)C2O)C1O 0.000 description 3
Abstract
The invention discloses a method for synthesizing sucralose-6-ethyl ester. The method comprises the following steps: synthesizing 4,6,1',6'-tetrachloro-4,6,1',6'-tetra-deoxy-galactose by adopting sucrose and chloride agent in a non-proton polar solvent at a certain temperature, and then adding carboxylate and reacting at a certain temperature, thereby generating the sucralose-6-ethyl ester. According to the method for synthesizing the sucralose-6-ethyl ester, the sucrose is taken as the raw material and the protection for hydroxyl groups is unneeded. The method has the characteristics of simple process, mild reaction condition, high productivity, high product purity and high yield. The production cost is low and the method is suitable for industrial production.
Description
Technical field
The present invention relates to organic compound method, more specifically, is the method for a kind of synthesizing trichloro-6-ethyl ester.
Background technology
Trichloro-cane-6-ethyl ester is the most important intermediates of synthesizing trichloro, and TGS i.e. 4,1 ', 6 '-three chloro-4,1 '; 6 '-three deoxidation sucralose are a kind of novel sweeteners, are exactly with sucrose 4,1 '; 6 ' hydroxyl selectivity chloro makes, and its sugariness is 600 times of sucrose, and it does not participate in body metabolism, and making us interested especially is the lower calorie of its tool; Can substitute the used asccharin in the variant prodn (like food, candy, beverage, cough drop) fully; The chemicalstability of TGS is good, is difficult for pyrolysis or hydrolysis reaction take place, and in acidic solution, has good stability especially, is a kind of rising sweeting agent.
Structure according to sucrose molecules can be known; Wherein the reactive behavior of each hydroxyl has nothing in common with each other; Therefore how on correct carbon atom, chlorination taking place is the difficult point of synthesizing trichloro-6-ethyl ester; And 6 primary hydroxyl is not substituted in final product, and this has also further deepened synthetic difficulty.At present existing a lot of synthesizing trichloros-6-ethyl ester method are mainly two big types of full radical protection method and single radical protection methods.Full radical protection method is because reaction process is too loaded down with trivial details, and reaction conditions is complicated, and the factor of required control is various, needs to consume and use a large amount of organic reagents, and is unfavorable for reclaiming, and is not widely used.Research about single radical protection method is a lot, like U.S. Pat 4889928, and US5449772, US5023329, US4950746 primary study sucrose-6-ethyl ester synthetic, but less to chlorating research; US4889928 has disclosed at pyridine and N, prepares sucrose-6-ethyl ester with acetic anhydride in the dinethylformamide, though it is higher to adopt pyridine to do the solvent yield; But long reaction time, and pyridine toxicity is big, smell heavy, aftertreatment is complicated, is unfavorable for environmental protection; In addition, cost is higher, is difficult for industriallization.Introduce among the US5023329 and be equipped with sucrose-6-ethyl ester with the Dibutyltin oxide legal system earlier; Obtain trichloro-cane-6-ethyl ester with the effect of Vilsmeier reagent again, but exist cost high, the solvent kind is too many; Be difficult for reclaiming, limitation such as complex process are difficult for realizing suitability for industrialized production.US4889928 has disclosed first employing trimethyl orthoacetate and the sucrose effect forms ring, and open loop under water, organic bases effect respectively again makes the ethanoyl migration to make TGS through chlorination, deacetylation again, and this method productive rate is also not too high.USP5498709 has introduced the preparation TGS and need not the process through full acidylate, simplified technological process, but the required azoformic acid isopropyl ester of esterification consumption is big, is unfavorable for reducing cost.
Summary of the invention
The object of the invention is to provide the method for a kind of synthesizing trichloro-6-ethyl ester, has the advantages that technology is simple, yield is high and production cost is low.
The present invention realizes through following technique means: to the high and high characteristics of transformation efficiency of sucrose chlorating selectivity in aprotic polar solvent; Select for use suitable chlorizating agent earlier with on the sucrose molecules 4; 6,1 ', 6 ' hydroxyl selective chlorination; Again with carboxylate salt with the chlorine esterification on 6, obtain trichloro-cane-6-ethyl ester.
The method of synthesizing trichloro of the present invention-6-ethyl ester comprises the steps:
(1) synthesizes 4,6,1 ', 6 '-tetrachloro-4; 6,1 ', 6 '-four deoxidation sucralose: in aprotic polar solvent, add sucrose earlier, add chlorination reagent again;-15 ℃～120 ℃ following stirring reactions 6～10 hours, wherein, the ratio of chlorination reagent and the molar weight of sucrose was greater than 7: 1; After reaction finishes, its PH is regulated to neutral in reaction solution cooling back, obtain 4,6 through extraction, underpressure distillation and vacuum-drying successively again, 1 ', 6 '-tetrachloro-4,6,1 ', 6 '-four deoxidation sucralose bullions, concrete reaction formula is following:
(2) synthesizing trichloro-6-ethyl ester: with above-mentioned 4,6,1 ', 6 '-tetrachloro-4,6; 1 ', 6 '-four deoxidation sucralose bullions mix with aprotic polar solvent, and in mixing solutions, add acetate, under nitrogen protection in 30～100 ℃ of following stirring reactions 6～8 hours; Wherein, the mole dosage of said carboxylate salt is 4,6,1 '; 6 '-tetrachloro-4,6,1～5 times of the mole dosage of 1 ', 6 '-four deoxidation sucralose; After reaction is accomplished, reaction solution successively through extract, decolour, filter, remove under reduced pressure solvent and with solids vacuum-drying after obtain the trichloro-cane-6-ethyl ester finished product, specifically reaction formula is following:
Optionally, used aprotic polar solvent is N in the method for synthesizing trichloro of the present invention-6-ethyl ester, dinethylformamide, a kind of in DMSO 99.8MIN. or the HMPA.
Optionally, used chlorination reagent is a kind of in sulfur oxychloride, phosgene, solid phosgene, phosphorus trichloride, tri-chlorination oxygen phosphorus or the phosphorus pentachloride in the method for synthesizing trichloro of the present invention-6-ethyl ester.
Optionally, used carboxylate salt is a kind of in sodium acetate, the potassium acetate in the method for synthesizing trichloro of the present invention-6-ethyl ester.
Preferably, used extraction agent is an ETHYLE ACETATE in the method for synthesizing trichloro of the present invention-6-ethyl ester.
Preferably, used discoloring agent is a gac in the method for synthesizing trichloro of the present invention-6-ethyl ester.
According to method synthesizing trichloro of the present invention-6-ethyl ester, utilize sucrose to be raw material, in aprotic polar solvent, add chlorination reagent synthetic 4,6 earlier; 1 ', 6 '-tetrachloro-4,6,1 ', 6 '-four deoxidation sucralose; This chlorination process is controlled easily, and the transformation efficiency of sucrose is more than 94%, because temperature of reaction is no more than 120 ℃, so there is not serious carbonization phenomenon; Thereby effectively controlled the content of impurity in the product, in addition, the reaction times is short, thereby has effectively shortened the production cycle; Add carboxylate salt synthesizing trichloro-6-ethyl ester again; Reaction conditions is gentle, and required time is short, need not in the whole process hydroxyl is carried out radical protection; Technology is simple, reaction conditions is gentle, reaction preference is high, product purity is high, yield is high and practice thrift cost, is fit to very much suitability for industrialized production.
Embodiment
Below describe several preferred implementation of the present invention, but be not in order to limit the present invention.
Embodiment 1:
According to following method synthesizing trichloro-6-ethyl ester:
(1) synthesizes 4,6,1 ', 6 '-tetrachloro-4; 6,1 ', 6 '-four deoxidation sucralose: the N that in the round-bottomed flask of 500ml, adds 100ml; Dinethylformamide (DMF) adds 25g sucrose again, is cooled to-10 ℃; Under vigorous stirring, be added dropwise to the 50g sulfur oxychloride in 1 hour, after dropwising, continue to be warming up to 110 ℃ gradually and continued stirring reaction 1 hour down; Reaction is cooled to 0 ℃ with reaction solution after finishing, and stirs 15 minutes, and dripping 100 milliliters of equivalent concentration is the ice-cold sodium hydroxide solution of 4N, regulates pH value to 9, and the pH value that adds the Glacial acetic acid min. 99.5 regulator solution again is to neutral; At last, in reaction solution, add 300 milliliters of extractions of ETHYLE ACETATE, water merges organic phase with 200 milliliters of ethyl acetate extractions twice, washing; Vacuum distillation recovered solvent, residue obtains 22.4g4 through high vacuum dry, and 6,1 '; 6 '-tetrachloro-4,6,1 ', 6 '-four deoxidation sucralose bullions.Concrete reaction formula is following:
(2) synthesizing trichloro-6-ethyl ester: with above-mentioned 22.4g4,6,1 ', 6 '-tetrachloro-4; The mixing of 6,1 ', 6 '-four deoxidation sucralose and 100 milliliters of DMF adds 7 gram sodium acetate, anhydrouss in mixing solutions; Under nitrogen protection, be warming up to 50 ℃, keep this temperature stirring reaction 6h, reaction finishes; Add 30 ml waters, 300 milliliters of ethyl acetate extractions, water merges organic phase and restrains decolorizing with activated carbon, filtration with 3 with 200 milliliters of ethyl acetate extractions twice; Remove solvent under reduced pressure and get the thick product 15.6g of sucrose-6-ethyl ester, with 150mL water recrystallization, the dry trichloro-cane-6-ethyl ester finished product 14.5g that gets, concrete reaction formula is following:
Embodiment 2:
According to following method synthesizing trichloro-6-ethyl ester:
(1) synthetic 4,6,1 ', 6 '-tetrachloro-4,6,1 ', 6 '-four deoxidation sucralose: with the 25g sucrose dissolved in 50 milliliters of DMF; To being equipped with mechanical stirrer, add 100 milliliters of DMF in 500 milliliter of four neck round-bottomed flask of TM and tap funnel, solution is chilled to-10 ℃, Dropwise 5 0g sulfur oxychloride under the vigorous stirring; Dropwise after 1 hour, this moment, solution had deposition to generate, and under this temperature, kept stirring 30 minutes; Drip the mixing solutions of sucrose and DMF, after being added dropwise to complete, slowly be warming up to 90 ℃ at 2 hours internal heating solution; Under this temperature, keep stirring 1 hour, in 2 hours, continue then slowly to be warming up to 110 ℃, under this temperature, keep stirring 1 hour; Reaction finishes, and solution is cooled to 0 ℃, stirs 15 minutes; Dripping 100 milliliters of equivalent concentration is the ice-cold sodium hydroxide solution of 4N, regulates pH value to 9, and the pH value that adds the Glacial acetic acid min. 99.5 regulator solution is to neutral; Add 300 milliliters of extractions of ETHYLE ACETATE at last, 200 milliliters of ethyl acetate extractions twice are used in water intaking mutually, merge organic phase, washing; Vacuum distillation recovered solvent, the residue high vacuum dry obtains 23.1g4, and 6; 1 ', 6 '-tetrachloro-4,6; 1 ', 6 '-four deoxidation sucralose bullions, concrete reaction equation is following:
(2) synthesizing trichloro-6-ethyl ester: with above-mentioned 23.1g4,6,1 ', 6 '-tetrachloro-4; 6,1 ', 6 '-four deoxidation sucralose are mixed with 100 milliliters of DMF, in mixing solutions, add 7 gram Glacial acetic acid potassium; Under nitrogen protection, be warming up to 50 ℃, keep this temperature stirring reaction 6h, reaction finishes the back and adds 30 ml waters, 300 milliliters of ethyl acetate extractions; 200 milliliters of ethyl acetate extractions twice are used in water intaking mutually, merge organic phase and restrain activated carbon decolorizings, filtration with 3; Remove solvent under reduced pressure and get the thick product 16.3g of sucrose-6-ethyl ester, get trichloro-cane-6-ethyl ester finished product 14.7g with 150mL water recrystallization after drying, concrete reaction formula is following:
For progressive of the present invention is described, the finished product of getting embodiment 1 and embodiment 2 carries out the test of aspects such as productive rate, purity, yield and production cycle, simultaneously, the common level that adopts prior art as a comparison, the result is as shown in table 1:
Table 1
In sum; The method of synthesizing trichloro of the present invention-6-ethyl ester compared to prior art, has that technology is simple, reaction conditions is gentle, productive rate is high, with short production cycle, product purity is high and yield is high characteristics; And production cost is low, is fit to very much suitability for industrialized production.
Claims (6)
1. the method for synthesizing trichloro-6-ethyl ester is characterized in that, comprises the steps:
(1) synthesizes 4,6,1 ', 6 '-tetrachloro-4; 6,1 ', 6 '-four deoxidation sucralose: in aprotic polar solvent, add sucrose earlier, add chlorination reagent again;-15 ℃～120 ℃ following stirring reactions 6～10 hours, wherein, the ratio of chlorination reagent and the molar weight of sucrose was greater than 7: 1; After reaction finishes, its PH is regulated to neutral in reaction solution cooling back, obtain 4,6 through extraction, underpressure distillation and vacuum-drying successively again, 1 ', 6 '-tetrachloro-4,6,1 ', 6 '-four deoxidation sucralose bullions, concrete reaction formula is following:
(2) synthesizing trichloro-6-ethyl ester: with above-mentioned 4,6,1 ', 6 '-tetrachloro-4,6; 1 ', 6 '-four deoxidation sucralose bullions mix with aprotic polar solvent, and in mixing solutions, add acetate, under nitrogen protection in 30～100 ℃ of following stirring reactions 6～8 hours; Wherein, the mole dosage of said carboxylate salt is 4,6,1 '; 6 '-tetrachloro-4,6,1～5 times of the mole dosage of 1 ', 6 '-four deoxidation sucralose; After reaction is accomplished, reaction solution successively through extract, decolour, filter, remove under reduced pressure solvent and with solids vacuum-drying after obtain the trichloro-cane-6-ethyl ester finished product, specifically reaction formula is following:
2. the method for synthesizing trichloro according to claim 1-6-ethyl ester is characterized in that, said aprotic polar solvent is N, dinethylformamide, DMSO 99.8MIN. or HMPA.
3. the method for synthesizing trichloro according to claim 1-6-ethyl ester is characterized in that, said chlorination reagent is sulfur oxychloride, phosgene, solid phosgene, phosphorus trichloride, tri-chlorination oxygen phosphorus or phosphorus pentachloride.
4. the method for synthesizing trichloro according to claim 1-6-ethyl ester is characterized in that, said carboxylate salt is sodium acetate, potassium acetate.
5. according to the method for 1 described synthesizing trichloro-6-ethyl ester before the right, it is characterized in that it is extraction agent that ETHYLE ACETATE is adopted in said extraction.
6. according to the method for 1 described synthesizing trichloro-6-ethyl ester before the right, it is characterized in that it is discoloring agent that gac is adopted in said decolouring.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105111250A (en) * | 2015-08-28 | 2015-12-02 | 山东康宝生化科技有限公司 | Method for preparing sucralose-6-ester by utilizing bis(trichloromethyl)carbonate |
| CN105153248A (en) * | 2015-08-28 | 2015-12-16 | 山东康宝生化科技有限公司 | Temperature control method applied in sucralose-6-ester synthesis process by Bis(trichlormethyl) carbonate method |
| WO2016127543A1 (en) * | 2015-02-11 | 2016-08-18 | 大连民族学院 | Sucrose ester-type cationic gene vector and preparation method therefor |
| CN112175022A (en) * | 2020-09-25 | 2021-01-05 | 万华化学集团股份有限公司 | Method for preparing sucralose-6-acetate by adopting microchannel reactor |
Citations (1)
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|---|---|---|---|---|
| US7932380B2 (en) * | 2008-03-06 | 2011-04-26 | Wanhe International (Group) Co. Ltd. | Process for the preparation of sucralose |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7932380B2 (en) * | 2008-03-06 | 2011-04-26 | Wanhe International (Group) Co. Ltd. | Process for the preparation of sucralose |
Non-Patent Citations (2)
| Title |
|---|
| ZHANG,JINGYU, ET AL.: ""Synthesis, Crystal Structure and Hydrolysis of a Novel Anhydrogalactosucrose: 2"-Methoxyl-O-1",4":3",6"-dianhydro-β-D-fructofuranosyl 3,6-anhydro-4-chloro-4-deoxy-α-D-galactopyranoside"", 《CHINESE JOURNAL OF CHEMISTRY》, vol. 29, no. 8, 24 August 2011 (2011-08-24), pages 1732 - 1738 * |
| 王艳丽，等。: ""三氯蔗糖-6-乙酯的合成工艺改进"", 《化工生产与技术》, vol. 15, no. 3, 1 September 2008 (2008-09-01), pages 28 - 30 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016127543A1 (en) * | 2015-02-11 | 2016-08-18 | 大连民族学院 | Sucrose ester-type cationic gene vector and preparation method therefor |
| 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 |
| US10279050B2 (en) | 2015-02-11 | 2019-05-07 | Dalian Nationalities University | Sucrose ester based cationic gene vector and preparation method thereof |
| CN105111250A (en) * | 2015-08-28 | 2015-12-02 | 山东康宝生化科技有限公司 | Method for preparing sucralose-6-ester by utilizing bis(trichloromethyl)carbonate |
| CN105153248A (en) * | 2015-08-28 | 2015-12-16 | 山东康宝生化科技有限公司 | Temperature control method applied in sucralose-6-ester synthesis process by Bis(trichlormethyl) carbonate method |
| CN112175022A (en) * | 2020-09-25 | 2021-01-05 | 万华化学集团股份有限公司 | Method for preparing sucralose-6-acetate by adopting microchannel reactor |
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Application publication date: 20120418 |