CN103319548A - Purification method for cane sugar-6-acetate - Google Patents
Purification method for cane sugar-6-acetate Download PDFInfo
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- CN103319548A CN103319548A CN2013102801866A CN201310280186A CN103319548A CN 103319548 A CN103319548 A CN 103319548A CN 2013102801866 A CN2013102801866 A CN 2013102801866A CN 201310280186 A CN201310280186 A CN 201310280186A CN 103319548 A CN103319548 A CN 103319548A
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Abstract
The invention provides a purification method for cane sugar-6-acetate. The purification method comprises the specific steps of: adding isoamylol in a cane sugar-6-acetate crude product on the condition of a reaction temperature of 20-80 DEG C; separating out crystals, and filtering; and drying the separated crystals in a vacuum drying box, wherein the volume ratio of isoamylol to the cane sugar-6-acetate crude product is 1: 1 to 5: 1. According to the purification method, isoamylol is used as an extraction agent, isoamylol is a polar solvent, and the polarity of cane sugar is greater than the polarity of cane sugar-6-acetate, so that cane sugar-6-acetate can be separated from isoamylol; moreover, the needed amount is low, the required temperature is low, and the requirement on equipment in industrial production is low; simultaneously, the purification method is high in economic benefits and meets the need of large-scale industrial production.
Description
Technical field
The present invention relates to a kind of method of purification of intermediate of Sucralose, especially a kind of method of purification of cane sugar-6-acetic ester.
Background technology
Sucralose, English name is Sucralose, is unique functional sweetener take sucrose as raw material, sugariness can reach more than 600 times of sucrose, be non-nutrition, efficient, without the sweeting agent of harm.
Sucralose is nonhygroscopic white crystalline powder, and chemical stability is very high in acidic solution, and is also fine at light, heat condition stability inferior, is soluble in ethanol, and specific refractory power and solubleness have good linear relationship.
Usually adopt at present " single radical protection method " to come final synthesizing trichloro.The advantage of this method is that single three steps of radical protection method can synthesize Sucralose, and step is few, and is simple to operate, requires also not high to processing unit.Its first step is exactly to adopt 6 of suitable esterifying reagent protections; obtain sucrose-6-ester; as seen sucrose-6-ester is the important intermediate of producing Sucralose; sucrose-6-ester synthetic is the committed step in three steps, improves quality and economic benefit that the productive rate of sucrose-6-ester and purity directly affect follow-up synthetic Sucralose.GB1543167 and GB2104063B have discussed the purposes of sucrose ester and Sucralose.
In the Sucralose synthetic method of bibliographical information, prepare the more of sucrose-6-ester by sucrose and esterifying agent, but less about the separation of sucrose-6-ester and purification, most of mixed solution of sucrose-6-ester that adopts is directly cooked the reaction of back, except cane sugar-6-acetic ester, also has unreacted raw material and byproduct of reaction in the mixed solution, for alleviating the burden of following process, reduce the cost of following process, the separating-purifying of Sucralose can be carried out smoothly, should carry out separating-purifying to it.
The US7626016 Purification of Suctose-6-acetate By The Method of Ion Exchanging, it is that the strong-acid ion exchange resin of 50mesh～100mesh is made sorbent material that this method is selected granularity, make eluent separating-purifying cane sugar-6-acetic ester with 70% aqueous acetone solution, this method needs a large amount of solvents, and the processing of ion exchange resin is cumbersome, and purity is also not too high; US20070227897 does recrystallization with anhydrous methanol under the reflux condition, then be cooled to room temperature, make crystal seed with cane sugar-6-acetic ester, spend the night cane sugar-6-acetic ester that must be purer, this method and US7932380, US4889928, US2011168568's is similar, and the time that these class methods need is long and under the condition of reflux, cane sugar-6-acetic ester crude product color can be deepened; Also have some document Purifying Sucrose-6-Acetate by Column Chromatographies, this class methods solvent for use amount is large, and the product loss is many.
Summary of the invention
Technical problem to be solved by this invention is to provide a kind of method of purification of cane sugar-6-acetic ester.
For solving the problems of the technologies described above, technical scheme of the present invention is:
A kind of method of purification of cane sugar-6-acetic ester, concrete steps are: be under the 20-80 ℃ of condition in temperature of reaction, in the cane sugar-6-acetic ester crude product, add primary isoamyl alcohol, treat that crystal separates out, filter, crystallize out is dry in vacuum drying oven, and the volume ratio of primary isoamyl alcohol and cane sugar-6-acetic ester crude product is 1:1-5:1.
Preferably, the method for purification of above-mentioned cane sugar-6-acetic ester, described cane sugar-6-acetic ester crude product is the brown color viscous liquid, is to remove most of DMF by the DMF solution of cane sugar-6-acetic ester under the condition of underpressure distillation to obtain.
Preferably, the method for purification of above-mentioned cane sugar-6-acetic ester, described temperature of reaction are 20-50 ℃.
Preferably, the method for purification of above-mentioned cane sugar-6-acetic ester, described temperature of reaction are 20 ℃.
Preferably, the method for purification of above-mentioned cane sugar-6-acetic ester, the volume ratio of described primary isoamyl alcohol and cane sugar-6-acetic ester crude product is 2:1-4:1.
Preferably, the method for purification of above-mentioned cane sugar-6-acetic ester, the volume ratio of described primary isoamyl alcohol and cane sugar-6-acetic ester crude product is 3:1.
The invention has the beneficial effects as follows:
The method of purification of above-mentioned cane sugar-6-acetic ester, select primary isoamyl alcohol to make extraction agent, primary isoamyl alcohol is polar solvent, the polarity of sucrose is greater than the polarity of cane sugar-6-acetic ester, and cane sugar-6-acetic ester can be separated out in primary isoamyl alcohol, and required amount and little, the temperature that requires is not high yet, lower to equipment requirements in the industrial production, have simultaneously higher economic benefit, be fit to the needs of large-scale commercial production.
Embodiment
Below in conjunction with specific embodiment technical scheme of the present invention is further described.
Experimental technique among the following embodiment if no special instructions, is ordinary method; Used test materials among the following embodiment if no special instructions, all can be bought from routine biochemistry reagent shop and obtain; Following detection method is liquid phase chromatography, carries out with reference to reference US4889928.
Embodiment 1
A kind of method of purification of cane sugar-6-acetic ester, concrete steps are:
The DMF solution of cane sugar-6-acetic ester is removed most of DMF under the condition of underpressure distillation, obtain the crude product of cane sugar-6-acetic ester, under 20 ℃ of conditions, add primary isoamyl alcohol, there are a large amount of crystal to separate out, filter, crystallize out is dry in vacuum drying oven, and the volume ratio of used primary isoamyl alcohol and cane sugar-6-acetic ester crude product is 3:1; Obtain cane sugar-6-acetic ester 3.7g, yield 82% is analyzed product with liquid chromatography, and cane sugar-6-acetic ester purity is 92%.
Wherein, according to liquid phase chromatography, with reference to reference US4889928, according to retention time cane sugar-6-acetic ester is confirmed, obtained its content value according to peak area ratio.Actual conditions is as follows: Zorbax NH
2Post, moving phase are V(water): the V(acetonitrile)=85:15, flow velocity 1.5mL/min, sample size 2 μ L, retention time sucrose: 3.46, sucrose-4-ester: 4.66, sucrose-6-ester 8.63.
Embodiment 2
A kind of method of purification of cane sugar-6-acetic ester, concrete steps are:
The DMF solution of cane sugar-6-acetic ester is removed most of DMF under the condition of underpressure distillation, obtain the crude product of cane sugar-6-acetic ester, under 20 ℃ of conditions, add primary isoamyl alcohol, there are a large amount of crystal to separate out, filter, crystallize out is dry in vacuum drying oven, and the volume ratio of used primary isoamyl alcohol and cane sugar-6-acetic ester crude product is 2:1; Obtain cane sugar-6-acetic ester 3.6g, yield 80% is analyzed product with liquid chromatography, and cane sugar-6-acetic ester purity is 90%.
Embodiment 3
A kind of method of purification of cane sugar-6-acetic ester, concrete steps are:
The DMF solution of cane sugar-6-acetic ester is removed most of DMF under the condition of underpressure distillation, obtain the crude product of cane sugar-6-acetic ester, under 30 ℃ of conditions, add primary isoamyl alcohol, there are a large amount of crystal to separate out, filter, crystallize out is dry in vacuum drying oven, and the volume ratio of used primary isoamyl alcohol and cane sugar-6-acetic ester crude product is 2:1; Obtain cane sugar-6-acetic ester 3.4g, yield 76% is analyzed product with liquid chromatography, and cane sugar-6-acetic ester purity is 80%.Along with the rising of temperature, the solubleness of cane sugar-6-acetic ester in primary isoamyl alcohol increases.
Embodiment 4
A kind of method of purification of cane sugar-6-acetic ester, concrete steps are:
The DMF solution of cane sugar-6-acetic ester is removed most of DMF under the condition of underpressure distillation, obtain the crude product of cane sugar-6-acetic ester, under 20 ℃ of conditions, add primary isoamyl alcohol, there are a large amount of crystal to separate out, filter, crystallize out is dry in vacuum drying oven, and the volume ratio of used primary isoamyl alcohol and cane sugar-6-acetic ester crude product is 4:1; Obtain cane sugar-6-acetic ester 3.5g, yield 78% is analyzed product with liquid chromatography, and cane sugar-6-acetic ester purity is 88%.
Embodiment 5
A kind of method of purification of cane sugar-6-acetic ester, concrete steps are:
The DMF solution of cane sugar-6-acetic ester is removed most of DMF under the condition of underpressure distillation, obtain the crude product of cane sugar-6-acetic ester, under 80 ℃ of conditions, add primary isoamyl alcohol, there are a large amount of crystal to separate out, filter, crystallize out is dry in vacuum drying oven, and the volume ratio of used primary isoamyl alcohol and cane sugar-6-acetic ester crude product is 5:1; Obtain cane sugar-6-acetic ester 3.2g, yield 71% is analyzed product with liquid chromatography, and cane sugar-6-acetic ester purity is 80%.
Embodiment 6
A kind of method of purification of cane sugar-6-acetic ester, concrete steps are:
The DMF solution of cane sugar-6-acetic ester is removed most of DMF under the condition of underpressure distillation, obtain the crude product of cane sugar-6-acetic ester, under 50 ℃ of conditions, add primary isoamyl alcohol, there are a large amount of crystal to separate out, filter, crystallize out is dry in vacuum drying oven, and the volume ratio of used primary isoamyl alcohol and cane sugar-6-acetic ester crude product is 3:1; Obtain cane sugar-6-acetic ester 3.4g, yield 76% is analyzed product with liquid chromatography, and cane sugar-6-acetic ester purity is 79%.
Embodiment 7
A kind of method of purification of cane sugar-6-acetic ester, concrete steps are:
The DMF solution of cane sugar-6-acetic ester is removed most of DMF under the condition of underpressure distillation, obtain the crude product of cane sugar-6-acetic ester, under 30 ℃ of conditions, add primary isoamyl alcohol, there are a large amount of crystal to separate out, filter, crystallize out is dry in vacuum drying oven, and the volume ratio of used primary isoamyl alcohol and cane sugar-6-acetic ester crude product is 3:1; Obtain cane sugar-6-acetic ester 3.5g, yield 78% is analyzed product with liquid chromatography, and cane sugar-6-acetic ester purity is 86%.
Embodiment 8
A kind of method of purification of cane sugar-6-acetic ester, concrete steps are:
The DMF solution of cane sugar-6-acetic ester is removed most of DMF under the condition of underpressure distillation, obtain the crude product of cane sugar-6-acetic ester, under 40 ℃ of conditions, add primary isoamyl alcohol, there are a large amount of crystal to separate out, filter, crystallize out is dry in vacuum drying oven, and the volume ratio of used primary isoamyl alcohol and cane sugar-6-acetic ester crude product is 4:1; Obtain cane sugar-6-acetic ester 3.4g, yield 76% is analyzed product with liquid chromatography, and cane sugar-6-acetic ester purity is 81%.
Comparative example 1
A kind of method of purification of cane sugar-6-acetic ester, concrete steps are:
The DMF solution of cane sugar-6-acetic ester is removed most of DMF under the condition of underpressure distillation, obtain the crude product of cane sugar-6-acetic ester, under 20 ℃ of conditions, add ethyl acetate, there is crystal to separate out, filter, crystallize out is dry in vacuum drying oven, and the volume ratio of used ethyl acetate and cane sugar-6-acetic ester crude product is 2:1; Obtain cane sugar-6-acetic ester 3.2g, yield 71% is analyzed product with liquid chromatography, and cane sugar-6-acetic ester purity is 80%.
Comparative example 2
A kind of method of purification of cane sugar-6-acetic ester, concrete steps are:
The DMF solution of cane sugar-6-acetic ester is removed most of DMF under the condition of underpressure distillation, obtain the crude product of cane sugar-6-acetic ester, under 20 ℃ of conditions, add methylene dichloride, there is crystal to separate out, filter, crystallize out is dry in vacuum drying oven, and the volume ratio of used methylene dichloride and cane sugar-6-acetic ester crude product is 2:1; Obtain cane sugar-6-acetic ester 3.5g, yield 78% is analyzed product with liquid chromatography, and cane sugar-6-acetic ester purity is 82%.
Comparative example 3
A kind of method of purification of cane sugar-6-acetic ester, concrete steps are:
Under 20 ℃ of conditions, in the DMF solution of cane sugar-6-acetic ester, add primary isoamyl alcohol, just begun to have crystal to separate out, very fast crystal disappears, and becomes solution, illustrates that the solubleness of DMF in primary isoamyl alcohol is very large.
The preparation method of the DMF solution of cane sugar-6-acetic ester in above-described embodiment and the comparative example is to synthesize with the method for Dibutyltin oxide, and concrete steps are:
(1) in three mouthfuls of round-bottomed flasks of 100ml, add sucrose 4.0g (11.68mmol), DMF(N, dinethylformamide) 14mL, heated and stirred is dissolved sucrose fully, is down to room temperature, obtains sucrose dissolved liquid stand-by; Add Dibutyltin oxide 3.06g (12.26mmol) and hexanaphthene 4mL in gained sucrose dissolved liquid, and install the top additional with the prolong of water trap, backflow 4-5h no longer includes the water generation to water trap; Reaction solution is cooled to 5 ℃, drips diacetyl oxide 1.31g (12.9mmol), temperature is lower than 10 ℃ in the dropping process, after dropwising, keeps thermotonus 1h;
(2) add a small amount of water in above-mentioned reaction solution, with the hexanaphthene extraction, lower floor is product, mainly is the DMF solution of cane sugar-6-acetic ester again; Organotin is separated out with the NaOH solution of 4mol/L in the upper strata, filters, and drying reclaims organotin.
Use Comparative Examples
The preparation sucralose-6-acetic ester:
(1) in three mouthfuls of reaction flask of the 100mL that magneton, condenser, thermometer are housed, add DMF10mL(0.13mol) and ethyl acetate 10mL(0.11mol), under the ice-water bath cooling and stirring, slowly drip sulfur oxychloride 6.64mL(0.09mol), the control dropping temperature dropwises rear 78 ℃ of backflows two hours that slowly are warming up to below 20 ℃, is down to room temperature, after leaving standstill a night, generate a large amount of needle-like white crystals in the solution.The DMF solution of this crystallization namely is Vilsimier reagent;
(2) cane sugar-6-acetic ester is dissolved in an amount of DMF solution, rear slowly being added drop-wise in the above-mentioned Vilsimier reagent, the ice-water bath cooling, the control dropping temperature slowly is warming up to 78 ℃ at 0～5 ℃ under the logical condition of nitrogen gas, reacts 1 hour; Rise to again 110 ℃, refluxed 3 hours; After reaction finishes, the ice-water bath cooling adds the sodium hydroxide solution of 4mol/L to neutral, after adding 50mL ethyl acetate fully stirs, filter, with the washing of 50mL ethyl acetate, filtrate is used 25mL * 4 ethyl acetate extractions, combined ethyl acetate layer to filter cake again, after ethyl acetate layer is used 25mL * 2 water washings again, add the 5g activated carbon decolorizing, concentrated under 60 ℃ of high-altitudes, get the sucralose-6-acetic ester concentrated solution.
Preparation result (total recovery of sucralose-6-acetic ester and purity) sees Table 1, wherein,
First group-usefulness Purification of Suctose-6-acetate By The Method of Ion Exchanging (US7626016);
Second group-under the reflux condition, do the cane sugar-6-acetic ester (US20070227897) that recrystallization must be purer with anhydrous methanol;
The 3rd group-embodiment 1 described cane sugar-6-acetic ester
The 4th group-cane sugar-6-acetic ester of not purifying
Table 1
| Grouping | Total recovery | Purity |
| First group | 37% | 94% |
| Second group | 38% | 95% |
| The 3rd group | 39.2% | 98% |
| The 4th group | 35% | 92% |
As seen, the second step of synthesizing trichloro be cane sugar-6-acetic ester through superchlorination synthesizing trichloro-6-acetic ester, sucrose is not arranged, sucrose-4-acetic ester in the cane sugar-6-acetic ester before not purifying, to lower one-step chlorination and purify unfavorable so that last Sucralose is difficult to recrystallization.
Above-mentioned detailed description of the method for purification of this a kind of cane sugar-6-acetic ester being carried out with reference to embodiment; illustrative rather than determinate; can list several embodiment according to institute's limited range; therefore in the variation and the modification that do not break away under the general plotting of the present invention, should belong within protection scope of the present invention.
Claims (6)
1. the method for purification of a cane sugar-6-acetic ester, it is characterized in that: concrete steps are: be under the 20-80 ℃ of condition in temperature of reaction, in the cane sugar-6-acetic ester crude product, add primary isoamyl alcohol, treat that crystal separates out, filter, crystallize out is dry in vacuum drying oven, and the volume ratio of primary isoamyl alcohol and cane sugar-6-acetic ester crude product is 1:1-5:1.
2. the method for purification of cane sugar-6-acetic ester according to claim 1, it is characterized in that: described cane sugar-6-acetic ester crude product is the brown color viscous liquid, is to remove most of DMF by the DMF solution of cane sugar-6-acetic ester under the condition of underpressure distillation to obtain.
3. the method for purification of cane sugar-6-acetic ester according to claim 1, it is characterized in that: described temperature of reaction is 20-50 ℃.
4. according to claim 1 or the method for purification of 3 described cane sugar-6-acetic esters, it is characterized in that: described temperature of reaction is 20 ℃.
5. the method for purification of cane sugar-6-acetic ester according to claim 1, it is characterized in that: the volume ratio of described primary isoamyl alcohol and cane sugar-6-acetic ester crude product is 2:1-4:1.
6. the method for purification of cane sugar-6-acetic ester according to claim 1 or 5, it is characterized in that: the volume ratio of described primary isoamyl alcohol and cane sugar-6-acetic ester crude product is 3:1.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106749440A (en) * | 2016-12-07 | 2017-05-31 | 广西科技大学 | It is a kind of by sucrose and the method for crystallising of the acetic acid esters of ortho-acetate synthesis of sucrose 6 |
| CN109593107A (en) * | 2018-12-10 | 2019-04-09 | 安徽金禾实业股份有限公司 | A kind of method of purification of cane sugar-6-acetic ester |
| CN111575327A (en) * | 2020-05-25 | 2020-08-25 | 安徽金禾实业股份有限公司 | Method for synthesizing sucrose-6-acetate by using rhizomucor miehei lipase as catalyst |
| CN113214330A (en) * | 2021-05-13 | 2021-08-06 | 安徽金禾化学材料研究所有限公司 | Purification and chlorination process of sucrose-6-ethyl ester |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106749440A (en) * | 2016-12-07 | 2017-05-31 | 广西科技大学 | It is a kind of by sucrose and the method for crystallising of the acetic acid esters of ortho-acetate synthesis of sucrose 6 |
| CN106749440B (en) * | 2016-12-07 | 2019-07-02 | 广西科技大学 | A kind of method for crystallising by sucrose and ortho-acetate synthesizing cane sugar-6-acetic ester |
| CN109593107A (en) * | 2018-12-10 | 2019-04-09 | 安徽金禾实业股份有限公司 | A kind of method of purification of cane sugar-6-acetic ester |
| CN111575327A (en) * | 2020-05-25 | 2020-08-25 | 安徽金禾实业股份有限公司 | Method for synthesizing sucrose-6-acetate by using rhizomucor miehei lipase as catalyst |
| CN113214330A (en) * | 2021-05-13 | 2021-08-06 | 安徽金禾化学材料研究所有限公司 | Purification and chlorination process of sucrose-6-ethyl ester |
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