CN103113426B - Method for preparing sweetening agent sucralose by one-pot process - Google Patents
Method for preparing sweetening agent sucralose by one-pot process Download PDFInfo
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- CN103113426B CN103113426B CN201310088065.1A CN201310088065A CN103113426B CN 103113426 B CN103113426 B CN 103113426B CN 201310088065 A CN201310088065 A CN 201310088065A CN 103113426 B CN103113426 B CN 103113426B
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- 235000019408 sucralose Nutrition 0.000 title claims abstract description 63
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 title claims abstract description 62
- 239000004376 Sucralose Substances 0.000 title claims abstract description 61
- 238000000034 method Methods 0.000 title claims abstract description 38
- 235000003599 food sweetener Nutrition 0.000 title abstract description 6
- 239000003765 sweetening agent Substances 0.000 title abstract description 6
- 238000005580 one pot reaction Methods 0.000 title abstract description 5
- 229930006000 Sucrose Natural products 0.000 claims abstract description 47
- 239000005720 sucrose Substances 0.000 claims abstract description 47
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims abstract description 32
- 238000006243 chemical reaction Methods 0.000 claims abstract description 23
- 239000002904 solvent Substances 0.000 claims abstract description 15
- 238000005660 chlorination reaction Methods 0.000 claims abstract description 10
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims abstract description 10
- 125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 27
- JKWMSGQKBLHBQQ-UHFFFAOYSA-N diboron trioxide Chemical compound O=BOB=O JKWMSGQKBLHBQQ-UHFFFAOYSA-N 0.000 claims description 20
- -1 sucrose ester Chemical class 0.000 claims description 18
- 239000004327 boric acid Substances 0.000 claims description 17
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 16
- 230000002378 acidificating effect Effects 0.000 claims description 14
- 239000003054 catalyst Substances 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 239000007788 liquid Substances 0.000 claims description 11
- 229920006395 saturated elastomer Polymers 0.000 claims description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- 239000000243 solution Substances 0.000 claims description 10
- 238000001514 detection method Methods 0.000 claims description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 8
- XCJXQCUJXDUNDN-UHFFFAOYSA-N chlordene Chemical compound C12C=CCC2C2(Cl)C(Cl)=C(Cl)C1(Cl)C2(Cl)Cl XCJXQCUJXDUNDN-UHFFFAOYSA-N 0.000 claims description 8
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 7
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 6
- 239000012074 organic phase Substances 0.000 claims description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 5
- 238000001816 cooling Methods 0.000 claims description 5
- 239000012043 crude product Substances 0.000 claims description 5
- 238000010438 heat treatment Methods 0.000 claims description 5
- 230000007062 hydrolysis Effects 0.000 claims description 5
- 238000006460 hydrolysis reaction Methods 0.000 claims description 5
- 229910017053 inorganic salt Inorganic materials 0.000 claims description 5
- 239000012266 salt solution Substances 0.000 claims description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 4
- 235000019270 ammonium chloride Nutrition 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 238000004321 preservation Methods 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 3
- 238000004821 distillation Methods 0.000 claims description 3
- 238000009413 insulation Methods 0.000 claims description 3
- 239000012071 phase Substances 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 3
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical class [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 2
- 238000011084 recovery Methods 0.000 claims description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 claims description 2
- 235000011152 sodium sulphate Nutrition 0.000 claims description 2
- 239000000047 product Substances 0.000 abstract description 18
- 239000002994 raw material Substances 0.000 abstract description 4
- 239000013067 intermediate product Substances 0.000 abstract description 2
- 239000002351 wastewater Substances 0.000 abstract description 2
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 abstract 2
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 abstract 1
- 239000003377 acid catalyst Substances 0.000 abstract 1
- 229910052796 boron Inorganic materials 0.000 abstract 1
- 230000000887 hydrating effect Effects 0.000 abstract 1
- 230000036571 hydration Effects 0.000 abstract 1
- 238000006703 hydration reaction Methods 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 238000004519 manufacturing process Methods 0.000 description 7
- 0 CCC(C(C1N=C)[U])[U]C1(*C)ClC(C)C(C(C)C(*)C(C)CN=C)N=C Chemical compound CCC(C(C1N=C)[U])[U]C1(*C)ClC(C)C(C(C)C(*)C(C)CN=C)N=C 0.000 description 6
- 150000008064 anhydrides Chemical class 0.000 description 5
- 238000005886 esterification reaction Methods 0.000 description 5
- 235000013305 food Nutrition 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 230000021736 acetylation Effects 0.000 description 3
- 238000006640 acetylation reaction Methods 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000006196 deacetylation Effects 0.000 description 3
- 238000003381 deacetylation reaction Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- HDPNBNXLBDFELL-UHFFFAOYSA-N 1,1,1-trimethoxyethane Chemical compound COC(C)(OC)OC HDPNBNXLBDFELL-UHFFFAOYSA-N 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 235000019658 bitter taste Nutrition 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- CCGKOQOJPYTBIH-UHFFFAOYSA-N ethenone Chemical compound C=C=O CCGKOQOJPYTBIH-UHFFFAOYSA-N 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 230000017105 transposition Effects 0.000 description 2
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 206010013786 Dry skin Diseases 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- MHABMANUFPZXEB-UHFFFAOYSA-N O-demethyl-aloesaponarin I Natural products O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=C(O)C(C(O)=O)=C2C MHABMANUFPZXEB-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- WXIUBYCJAAEOFL-UHFFFAOYSA-N [S].ClOCl Chemical class [S].ClOCl WXIUBYCJAAEOFL-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
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- 235000008429 bread Nutrition 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
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- 239000006227 byproduct Substances 0.000 description 1
- 235000012970 cakes Nutrition 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 229940112822 chewing gum Drugs 0.000 description 1
- 208000012839 conversion disease Diseases 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
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- 206010012601 diabetes mellitus Diseases 0.000 description 1
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- 235000013399 edible fruits Nutrition 0.000 description 1
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- 239000000706 filtrate Substances 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
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- 230000003914 insulin secretion Effects 0.000 description 1
- 235000015094 jam Nutrition 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008274 jelly Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000007886 mutagenicity Effects 0.000 description 1
- 231100000299 mutagenicity Toxicity 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 235000013615 non-nutritive sweetener Nutrition 0.000 description 1
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- 238000011017 operating method Methods 0.000 description 1
- 235000011962 puddings Nutrition 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 125000000185 sucrose group Chemical group 0.000 description 1
- 150000003445 sucroses Chemical class 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000019605 sweet taste sensations Nutrition 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
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- Saccharide Compounds (AREA)
Abstract
The invention relates to a method for preparing a sweetening agent sucralose by a one-pot process. The method comprises the following steps of: protecting sucrose which is taken as a raw material by sucrose-6-hydroxyl through boron anhydrous with presence of an acid catalyst and a solvent, directly implementing a chlorination through thionyl chloride without separating disucrose borate which is an intermediate product to obtain hexachloro disucrose borate, and hydrating to obtain the sucralose. The method disclosed by the invention sequentially implements three reactions, namely selective protection, chloro reaction and hydration, of the sucrose-6-hydroxyl in one pot to prepare the sucralose, and the process is simple and convenient and reduces discharge of wastewater; and the prepared sucralose product is high in purity, high in yield, low in cost, and suitable for industrial production.
Description
Technical field
The present invention relates to a kind of production method of Sweetener Sucralose, particularly relate to the method utilizing boric anhydride one kettle way to prepare Sucralose, belong to foodstuff additive production technical field.
Background technology
Sucralose (Trichlorosucrose) is a kind of halo sucrose derivative, chemical name is 1 ', 6 '-two chloro-1 ', 6 '-dideoxy-chloro-4-the deoxidation of beta-D-fructofuranose-4--2-D-pyranofructose, be developed by Tai Lai company of Britain (Tate & Lyle) and London University Hough professor L, proposed the patent application of novel sweetener in 1976.The structural formula of Sucralose is as follows:
Sucralose
The mouthfeel alcohol of Sucralose and strong, very close to sucrose, sweet taste characteristic curve is almost overlapping with sucrose, and without any bitter taste, and sugariness can reach 600 times of sucrose.Sucralose is white crystalline powder, fusing point 130 degree, soluble in water and alcohol, and non-foaming in dissolution process, Sucralose is very stable, can preserve 4 years under room temperature in dry environment, even if in acidic aqueous solution, stores and also can not change for 1 year.Sucralose both can be used alone, also can be used in combination with other sweeting agent, in use not only can not produce detrimentally affect to food, can also cover the unpleasant tastes such as the bitterness of some foods.In addition, Sucralose has unique advantage, as low in Sucralose institute heat content, not easily digested absorption, is not easy to produce carious tooth, can causes various diseases unlike fructose and maltose; Sucralose is as a kind of non-nutritive sweeteners, and itself noenergy, sugariness are high, can supply cardiovascular diseases and patients with diabetes mellitus; Simultaneously Sucralose safety performance is high, and toxicological study shows that it does not have teratogenecity, mutagenicity, carinogenicity, breeding toxicity and neurotoxicity, also has no effect to the glucose level of animal and insulin secretion.
19th-century the mid-80, Sucralose accepts world security team for evaluation, and research shows it to fish and hydrobiont all without harm, and biodegradable, confirms that it is safe for extensive use.Canada in 1991 takes the lead in ratifying to use Sucralose, and on July 1st, 1997, approval used in China, and U.S. food Drug Administration ratifies Sucralose and uses as foodstuff additive on March 21st, 1998.Current Sucralose is widely used in the food such as beverage, chewing gum, milk-product, preserved fruit, syrup, bread, cake, ice-creams, jam, jelly, pudding.Sucralose, as the representative products of sweeting agent, is the superpower sweeting agent of non-nutritive best up to now, the huge market demand.But Sucralose output in domestic is low, and great majority depend on import, Sucralose is thus caused only to can not get widespread use for luxury food.
The preparation method of Sucralose mainly contains tritylation method, mono-esterification method, sucrose derivative chlorination process, biological process and cottonseed trisaccharide method, above method synthesis step is many, technical process is complicated, and chemical-enzymatic ferments loaded down with trivial details and is difficult to the purifying carrying out intermediate product.Mono-esterification method is only had to have suitability for industrialized production meaning in above method; the method take sucrose as starting raw material; trimethyl orthoacetate protection, transposition prepares cane sugar-6-acetic ester monoesters, and then chloro, deacetylation obtain Sucralose, and chemical equation is as follows:
The method uses trimethyl orthoacetate to protect 4,6-dihydroxyl of sucrose are two under low temperature, produces methyl alcohol simultaneously.And the methyl alcohol existed in system causes this step reaction conversion ratio low, and attempt to remove methyl alcohol can produce a large amount of transesterify by products, so this step yield only has about 50% by heating up.And need to utilize TERTIARY BUTYL AMINE-aqueous systems transposition to prepare mono-esterification product cane sugar-6-acetic ester, aftertreatment is complicated, is unfavorable for suitability for industrialized production.
Chinese patent document CN101812095A discloses a kind of acetylation reagent that adopts to prepare the method for Sucralose; comprise three steps: (one) acylation reaction; sucrose and acetylation reagent react and generate cane sugar-6-acetic ester; (2) chlorination reaction; cane sugar-6-acetic ester obtained in the previous step is obtained sucralose-6-acetic ester through chlorination reaction; (3) deacetylation, obtains Sucralose by sucralose-6-acetic ester obtained in the previous step through deacetylation.Select ketene gas as acetylation reagent in the acylation reaction of this technical scheme, ketene is dangerous raw material, operation inconvenience.And acidylate, chlorination, hydrolysis three step operating procedure are numerous and diverse, are unfavorable for suitability for industrialized production.
Summary of the invention
For the deficiencies in the prior art, the invention provides a kind of simple process, method that one kettle way that product yield is high prepares Sweetener Sucralose.
The present invention a kind ofly utilizes boric anhydride to carry out the protection of sucrose-6-hydroxyl selectivity list and then chloro prepares the method for Sucralose.
Technical scheme of the present invention is as follows:
A kind of method of preparation formula (I) Sucralose, by boric acid two sucrose ester making formula (II) sucrose obtain formula (III) in the presence of acidic with boric anhydride esterification,
This boric acid two sucrose ester without separation, in same reactor directly with boric acid chlordene two sucrose ester of sulfur oxychloride chlorination preparation formula (IV), be then hydrolyzed and prepare Sucralose (I).
Specifically, a kind of method preparing Sucralose, comprises step as follows:
(1), under nitrogen protection, in the reaction vessel of drying, solvent, sucrose, an acidic catalyst is added successively,
(2) at temperature is 0 DEG C ~ 10 DEG C, add boric anhydride, 10 DEG C ~ 20 DEG C insulation reaction 2 ~ 4 hours, Liquid Detection sucrose inversion is complete, generates boric acid two sucrose ester; Then,
(3) at temperature-10 DEG C ~ 20 DEG C, drip sulfur oxychloride, from 20 DEG C to 150 DEG C, heating and heat preservation carries out chlorination stage by stage, generates boric acid chlordene two sucrose ester, and Liquid Detection chloro transforms completely, underpressure distillation recovery part solvent, cooling,
(4) add saturated inorganic salt solution hydrolysis boric acid chlordene two sucrose ester and generate Sucralose, be extracted with ethyl acetate, after organic phase saturated sodium-chloride water solution washes twice, organic phase anhydrous sodium sulfate drying, filter, reclaim ethyl acetate, obtain Sucralose crude product;
(5) by Sucralose crude product 95wt% ethanol and activated carbon decolorizing, filtered while hot, Sucralose sterling is separated out in cooling.
According to the present invention, preferably, the solvent in step (1) is DMF (DMF) or N,N-dimethylacetamide (DMAC), and the amount of solvent and the mass ratio of described sucrose are solvent: sucrose=4 ~ 15:1.
According to the present invention, preferably, an acidic catalyst described in step (1) is one of p-methyl benzenesulfonic acid, Phenylsulfonic acid, methylsulphonic acid, the vitriol oil, trifluoroacetic acid or combination.The mol ratio of preferred described acidic catalyst dosage and sucrose is 0.001 ~ 0.02:1.The mol ratio of further preferred described acidic catalyst dosage and sucrose is 0.005 ~ 0.01:1.
The above vitriol oil has implication well known in the art, is the sulphuric acid soln that mass percent is more than or equal to 70%.
According to the present invention, preferably, add the mol ratio of the sucrose of boric anhydride and step (1) in step (2) for (0.3 ~ 0.5): 1, further preferred boric anhydride: the mol ratio of sucrose is (0.35 ~ 0.45): 1.
According to the present invention, preferably, the temperature adding boric anhydride in step (2) is 5 DEG C ~ 6 DEG C, is incubated 15 DEG C of 2 ~ 3 hours reaction times.As Liquid Detection sucrose inversion not exclusively then can the proper extension reaction times.
According to the present invention, preferably, add boric anhydride in step (2) is add in batches, and 2 ~ 4 batches is good, interval 30min.
According to the present invention, preferably, step (3) drips 0 DEG C ~ 10 DEG C that the temperature of sulfur oxychloride is, preferably 5 DEG C further.
According to the present invention, preferably, the heating and heat preservation reaction stage by stage described in step (3) is that point three phases carries out: 20 DEG C ~ 30 DEG C reaction 2 ~ 3h, 70 DEG C ~ 90 DEG C reaction 2 ~ 3h, 120 DEG C ~ 150 DEG C reaction 3 ~ 4h.As the conversion of Liquid Detection chloro not exclusively then can the proper extension reaction times.
According to the present invention, preferably, the saturated inorganic salt solution described in step (4) is saturated sodium-chloride water solution, saturated aqueous ammonium chloride, saturated potassium chloride solution or saturated aqueous sodium sulfate; Preferred saturated sodium-chloride water solution further.
Liquid Detection described in the inventive method utilizes liquid chromatograph (UV-detector) to carry out reaction monitoring and purity detecting.By prior art.
Technical characterstic of the present invention is: utilize boric anhydride at solvent (N; dinethylformamide or N; N-N,N-DIMETHYLACETAMIDE), selective protection is carried out to sucrose under acidic catalyst, the preferential and boric anhydride esterification of low steric hindrance, highly active sucrose-6-position hydroxyl, obtains boric acid two sucrose ester.This boric acid two sucrose ester is without separation, at N, dinethylformamide or N, directly drip sulfur oxychloride under N-dimethylacetamide amine system and carry out chlorination, and according to the activity difference of hydroxyl stage by stage intensification chloro prepare boric acid chlordene two sucrose ester, then utilize boric acid ester to be easy to the characteristic be hydrolyzed and Sucralose is soluble in water, directly add the hydrolysis of saturated inorganic salt solution, one kettle way prepares Sucralose.The present invention by 6-position hydroxyl protection, the chloro of sucrose, be hydrolyzed and carry out in one pot, technological process is easy, and product yield is high.
Method reaction formula of the present invention is as follows:
Excellent results of the present invention is: Sucralose product yield is high, simple process environmental protection.The present invention, in same reactor, utilizes boric anhydride under solvent DMF, acidic catalyst, and the hydroxyl selective protection of-6-of sucrose position, chloro, hydrolysis three kinds are reacted in one pot and completed successively; product yield is high; technological process is easy, and decreases discharge of wastewater, economic environmental protection.The Sucralose product purity prepared with this one kettle way is high, and HPLC purity can reach more than 99.0%, and yield can up to more than 80%, and cost is low, is suitable for suitability for industrialized production, significant to the commercial production levels improving China's Sucralose.
Accompanying drawing explanation
Fig. 1 is the HPLC chromatograms of Sucralose standard substance, and Fig. 2 is that embodiment 1 utilizes boric anhydride one kettle way to obtain the HPLC chromatograms of Sucralose sample.
Embodiment
Describe the present invention in detail below in conjunction with embodiment, but the present invention is not only confined to this.
In embodiment, starting raw material sucrose is white crystalline powder solid, and moisture content is less than 1000ppm, commercial products.Liquid Detection: utilize Shimadzu liquid chromatograph to carry out reaction monitoring and purity detecting, INSTRUMENT MODEL is LC-20AT, and chromatographic column is C18 post ODS (250mm × 4.6mm × 5 μm), and moving phase is acetonitrile: water=85:15 volume ratio; Determined wavelength is 220nm.
Embodiment 1
Under nitrogen protection, in 1000 milliliters of glass flask of drying, add 200 grams of DMFs, 34.2 grams of (0.1 mole) sucrose, 0.14 gram of p-methyl benzenesulfonic acid successively.Keep 0 DEG C ~ 10 DEG C, add 2.31 grams of (0.034 mole) boric anhydrides in batches, 10 DEG C ~ 20 DEG C insulation reaction 3 hours, Liquid Detection sucrose inversion is complete; Then frozen water cooling, keep 0 DEG C ~ 10 DEG C, drip 39.3 grams of (0.33 mole) sulfur oxychlorides, drip and finish, temperature reaction stage by stage, in 20 DEG C ~ 30 DEG C stirring reactions 2 hours, 70 DEG C ~ 90 DEG C stirring reactions 2 hours, 120 DEG C ~ 150 DEG C stirring reactions 3 hours, about 150 grams of solvents are reclaimed in underpressure distillation, are cooled to room temperature.Add 120 grams of saturated sodium-chloride water solutions, stirred at ambient temperature is hydrolyzed 3 hours; Add extraction into ethyl acetate three times, share ethyl acetate 130 grams, merge organic phase, wash twice with 30 grams of saturated sodium-chloride water solutions, thoroughly remove boric acid.Organic phase 12 grams of anhydrous sodium sulfate dryings, filter, and reclaim ethyl acetate, obtain Sucralose crude product.Add 60 gram of 95% ethanol and 1 gram of gac 70 DEG C decolouring 30 minutes, filtered while hot, filtrate cools, and filter, obtain 33.1 grams of Sucraloses, crystalline white powder solid, purity is 99.1%, yield 83.3%, and fusing point is 84 ~ 85 DEG C.Product passes through and standard substance comparison, and sample retention time is identical, see accompanying drawing 1, Fig. 2.
Embodiment 2
As described in Example 1, difference is, an acidic catalyst selects methylsulphonic acid, and replace 0.14 gram of p-methyl benzenesulfonic acid in embodiment 1 to react with 80 milligrams of methylsulphonic acids, preparation process and condition are with embodiment 1, and products obtained therefrom purity and yield are in table 1.
Embodiment 3
As described in Example 1, difference is, an acidic catalyst selects 98% vitriol oil, and replace 0.14 gram of p-methyl benzenesulfonic acid in embodiment 1 to react with 80 milligram of 98% vitriol oil, preparation process and condition are with embodiment 1, and products obtained therefrom purity and yield are in table 1.
Embodiment 4
As described in Example 1, difference is, an acidic catalyst selects trifluoroacetic acid, and replace 0.14 gram of p-methyl benzenesulfonic acid in embodiment 1 to react with 91 milligrams of trifluoroacetic acids, preparation process and condition are with embodiment 1, and products obtained therefrom purity and yield are in table 1.
Embodiment 5
As described in Example 1, difference is, sucrose is different from the mol ratio of boric anhydride, and replace 2.31 grams of boric anhydrides in embodiment 1 to react with 2.65 grams of boric anhydrides, preparation process and condition are with embodiment 1, and products obtained therefrom purity and yield are in table 1.
Embodiment 6
As described in Example 1, difference is, sucrose is different from the mol ratio of boric anhydride, and replace 2.31 grams of boric anhydrides in embodiment 1 to react with 2.04 grams of boric anhydrides, preparation process and condition are with embodiment 1, and products obtained therefrom purity and yield are in table 1.
Embodiment 7
As described in Example 1, difference is, with N, N-N,N-DIMETHYLACETAMIDE, as solvent, replaces 200 grams of N in embodiment 1 with 200 grams of N,N-dimethylacetamide, dinethylformamide reacts, and preparation process and condition are with embodiment 1, and products obtained therefrom purity and yield are in table 1.
Embodiment 8
As described in Example 1, difference is, boric acid chlordene two sucrose ester hydrolysis is carried out with saturated aqueous ammonium chloride, 120 grams of saturated sodium-chloride water solutions in embodiment 1 are replaced to be hydrolyzed with 120 grams of saturated aqueous ammonium chlorides, preparation process and condition are with embodiment 1, and products obtained therefrom purity and yield are in table 1.
The Sucralose that table 1, the present invention utilize boric anhydride one kettle way to prepare
Claims (9)
1. prepare a method for Sucralose, comprise step as follows:
(1), under nitrogen protection, in the reaction vessel of drying, solvent, sucrose, an acidic catalyst is added successively;
Described solvent is DMF or N,N-dimethylacetamide;
Described an acidic catalyst is one of p-methyl benzenesulfonic acid, Phenylsulfonic acid, methylsulphonic acid, the vitriol oil, trifluoroacetic acid or combination;
The mol ratio of described acidic catalyst dosage and sucrose is 0.001 ~ 0.02:1;
(2) at temperature is 0 DEG C ~ 10 DEG C, add boric anhydride, the mol ratio adding the sucrose of boric anhydride and step (1) is (0.3 ~ 0.5): 1,10 DEG C ~ 20 DEG C insulation reaction 2 ~ 4 hours, and Liquid Detection sucrose inversion is complete, generates boric acid two sucrose ester; Then,
This boric acid two sucrose ester without separation, in same reactor directly and sulfur oxychloride chlorination prepare boric acid chlordene two sucrose ester:
(3) at temperature-10 DEG C ~ 20 DEG C, drip sulfur oxychloride, from 20 DEG C to 150 DEG C, heating and heat preservation carries out chlorination stage by stage, generates boric acid chlordene two sucrose ester, and Liquid Detection chloro transforms completely, underpressure distillation recovery part solvent, cooling,
(4) add saturated inorganic salt solution hydrolysis boric acid chlordene two sucrose ester and generate Sucralose, be extracted with ethyl acetate, after organic phase saturated sodium-chloride water solution washes twice, organic phase anhydrous sodium sulfate drying, filter, reclaim ethyl acetate, obtain Sucralose crude product;
(5) by Sucralose crude product 95wt% ethanol and activated carbon decolorizing, filtered while hot, Sucralose sterling is separated out in cooling.
2. prepare the method for Sucralose as claimed in claim 1, it is characterized in that the amount of solvent described in step (1) and the mass ratio of described sucrose are solvent: sucrose=4 ~ 15:1.
3. prepare the method for Sucralose as claimed in claim 1, it is characterized in that the mol ratio of the sucrose adding boric anhydride and step (1) in step (2) is for (0.35 ~ 0.45): 1.
4. prepare the method for Sucralose as claimed in claim 1, the temperature that it is characterized in that adding in step (2) boric anhydride is 5 DEG C ~ 6 DEG C, is incubated 15 DEG C of 2 ~ 3 hours reaction times.
5. prepare the method for Sucralose as claimed in claim 1, it is characterized in that adding in step (2) boric anhydride and be points 2 ~ 4 batches and add, interval 30min.
6. prepare the method for Sucralose as claimed in claim 1, it is characterized in that the temperature of step (3) dropping sulfur oxychloride is 0 DEG C ~ 10 DEG C.
7. prepare the method for Sucralose as claimed in claim 1, it is characterized in that the temperature of step (3) dropping sulfur oxychloride is 5 DEG C.
8. prepare the method for Sucralose as claimed in claim 1, it is characterized in that the heating and heat preservation reaction stage by stage described in step (3) is that point three phases carries out: 20 DEG C ~ 30 DEG C reaction 2 ~ 3h, 70 DEG C ~ 90 DEG C reaction 2 ~ 3h, 120 DEG C ~ 150 DEG C reaction 3 ~ 4h.
9. prepare the method for Sucralose as claimed in claim 1, it is characterized in that the saturated inorganic salt solution described in step (4) is saturated sodium-chloride water solution, saturated aqueous ammonium chloride, saturated potassium chloride solution or saturated aqueous sodium sulfate.
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Denomination of invention: Method for preparing Sweetener Sucralose by one pot method Effective date of registration: 20211229 Granted publication date: 20150121 Pledgee: Shandong Tonghong import and Export Co.,Ltd. Pledgor: Xinfa pharmaceutical Co.,Ltd. Registration number: Y2021980016873 |
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Denomination of invention: One-pot method for preparing sweetener sucralose Effective date of registration: 20220729 Granted publication date: 20150121 Pledgee: Industrial and Commercial Bank of China Co., Ltd. Dongying Kenli Sub-branch Pledgor: Xinfa pharmaceutical Co.,Ltd. Registration number: Y2022980011404 |
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