WO2023279278A1 - 三氯蔗糖-6-酯的提纯方法 - Google Patents

三氯蔗糖-6-酯的提纯方法 Download PDF

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WO2023279278A1
WO2023279278A1 PCT/CN2021/104939 CN2021104939W WO2023279278A1 WO 2023279278 A1 WO2023279278 A1 WO 2023279278A1 CN 2021104939 W CN2021104939 W CN 2021104939W WO 2023279278 A1 WO2023279278 A1 WO 2023279278A1
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crystallization
ester
sucralose
filtrate
aqueous solution
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PCT/CN2021/104939
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English (en)
French (fr)
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杨志健
陈永乐
慈昊
仇鑫
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安徽金禾实业股份有限公司
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Priority to CN202180002111.4A priority Critical patent/CN113677689B/zh
Priority to PCT/CN2021/104939 priority patent/WO2023279278A1/zh
Publication of WO2023279278A1 publication Critical patent/WO2023279278A1/zh

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H5/00—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium
    • C07H5/02—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium to halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00—Processes for the preparation of sugar derivatives
    • C07H1/06—Separation; Purification

Definitions

  • the invention belongs to the technical field of fine chemicals, and in particular relates to a method for purifying sucralose-6-ester.
  • Sucralose-6-ester is one of the main intermediates for the synthesis of sucralose, which can be obtained from sucrose through esterification, chlorination and deesterification.
  • the traditional green chlorination process is that sucrose-6-ester is prepared by high-temperature chlorination of thionyl chloride in N,N-dimethylformamide (DMF) and trichloroethane as solvents. Since the usage amount of the chlorination reagent thionyl chloride is much higher than the equimolar usage amount of theoretical chlorination, and the chlorination temperature is higher (>100° C.), the resulting chlorination solution has more impurities.
  • DMF N,N-dimethylformamide
  • the esterification agent as acetic acid as an example
  • sucralose-6-ethyl ester there are also a large amount of sucralose diester, sucralose-6-ethyl ester, and a small amount of sucralose-6-ethyl ester. esters and sucralose-6-ethyl ester, etc.
  • sucralose-6-ethyl ester it is often necessary in industry to prepare sucralose-6-ethyl ester through multi-step purification, and then hydrolyze with methanol/sodium methoxide to obtain three sucralose.
  • Patent CN103012509 carries out salting-out purification of sucralose-6-ethyl ester by adding inorganic salts, and the addition amount is 6-12wt% of the mother liquor, regardless of whether this process can completely remove sucralose-6-ethyl ester from chlorine
  • the high-salt wastewater with extremely high salt content needs to be treated later, which seriously affects the practical value of this patent.
  • sucralose-6-ethyl ester is the traditional way of separating impurities in chlorinated liquids. This method has high energy consumption, low efficiency, and produces a large amount of waste. Liquid, low economic value and other defects, and the yield of sucralose-6-ethyl ester is low, there is an urgent need for a purification method of sucralose-6-ester to solve the above problems.
  • the present application is proposed in order to provide a method for purifying sucralose-6-ester which overcomes the above problem or at least partly solves the above problem.
  • a method for purifying sucralose-6-ester comprising:
  • Concentration step Concentrate the mother liquor to be purified to remove the organic solvent. After the concentration is completed, add water to it to form an aqueous solution to be purified; wherein, the mother liquor to be purified is prepared by neutralizing sucralose through esterification and chlorination. The reaction solution of sucralose-6-ester is obtained;
  • Oxidation step adding an oxidizing agent and a decolorizing agent in sequence to the aqueous solution to be purified to carry out an oxidative decolorization reaction, and then adding an alkali hydrolysis agent to the aqueous solution to be purified to oxidize the target impurity to sucralose-6-ester, and remove colored impurities; after a period of reaction, solid-liquid separation is carried out to obtain solid waste and the first filtrate; and
  • Crystallization step after adjusting the first filtrate to neutrality, adding an extractant, performing extraction and crystallization at the same time, to obtain the crude product of sucralose-6-ester and the second filtrate.
  • the method also includes:
  • Filtrate recovery step layering the second filtrate to obtain the first organic phase and the first water phase, evaporating the first organic phase to remove the extractant to obtain sugar residue, adding water to dissolve, and separating solid and liquid to obtain sugar slag aqueous solution;
  • the aqueous solution of sugar residue is mixed with the first water phase, and an extractant is added for extraction, and the second organic phase obtained by extraction is recovered into the first filtrate to enter the crystallization step.
  • the ratio of the added mass of water to the mass of the first organic phase is 0.5-2:1, the dissolving temperature is 40-70°C, and the dissolving time is 0.5-2:1. 2h;
  • the volume ratio of the extraction agent to the total volume of the sugar residue aqueous solution and the first water phase is 0.1-1:1.
  • the method also includes:
  • Refining step dissolving the obtained crude product of sucralose-6-ester in an extractant, performing first crystallization and separation to obtain intermediate crystals and a third filtrate;
  • the method also includes:
  • the fourth filtrate is recycled into the mother liquor to be purified which will enter the concentration step.
  • the ratio of the mass dosage of the extractant to the mass of the crude product of sucralose-6-ester is 2 to 5:1; the crystallization temperature of the first crystallization is -5 ⁇ 10°C, the crystallization time is 0.5 ⁇ 3h;
  • the ratio of the mass dosage of water to the mass of the intermediate crystal is 2-5:1; the crystallization temperature of the second crystallization is 0-30°C, and the crystallization time is 1-5h.
  • the concentration temperature is 60-80°C, and the vacuum degree is -0.1--0.05Mpa;
  • the configured volume of the aqueous solution to be purified is 0.5 to 1 times the volume of the mother liquor to be purified.
  • the oxidizing agent is one of sodium hypochlorite, sodium chlorate and calcium hypochlorite, preferably sodium hypochlorite;
  • the dosage of the oxidizing agent is 1-1.5 times of the total mass of the target impurities in the mother liquor to be purified.
  • the decolorizing agent is one or more of activated carbon, attapulgite, diatomite and activated clay, preferably activated carbon;
  • the consumption of decolorizing agent is 0.05 ⁇ 0.2wt% of the aqueous solution to be purified
  • the temperature of the oxidation decolorization reaction is 40-60° C., and the reaction time is 1-4 hours.
  • the alkaline hydrolysis agent is ammonia water or NaOH, preferably ammonia water;
  • the consumption of alkaline hydrolysis agent is based on adjusting the pH value of the aqueous solution to be purified to 8.5-10.5.
  • adjusting the first filtrate to neutrality includes:
  • the pH value of the first filtrate is adjusted to 6.5-8.0 by using an acidic substance; wherein, the acidic substance is dilute hydrochloric acid or dilute sulfuric acid, preferably dilute hydrochloric acid.
  • the extractant is one or more of methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and isobutyl acetate, Preferably ethyl acetate;
  • the ratio of the volumetric dosage of the extractant to the volume of the aqueous solution to be purified is 1:1 ⁇ 3;
  • the crystallization temperature is -10-10°C, and the crystallization time is 6-12 hours.
  • the beneficial effect of the present application is that the present application treats the chlorination reaction neutralization solution for the preparation of sucralose-6-ester through the combined use of oxidizing agent and alkaline hydrolysis agent, so that the impurities sucralose diester and tetrachloralose -6-ester is converted into the target product sucralose-6-ester, which greatly improves the yield of the target product while effectively removing the impurity content; and the overall treatment process is simple and smooth, with low economic cost and practicality Strong; the obtained sucralose-6-ester has high purity and can be directly used for the production of sucralose; and can significantly reduce the impurity content of waste water, ease the pressure of subsequent waste water treatment, and have a high degree of environmental friendliness. application and economic value.
  • Figure 1 shows a schematic flow diagram of a method for purifying sucralose-6-ester according to an embodiment of the present application
  • Figure 2 shows a schematic structural view of a purification device for sucralose-6-ester according to an embodiment of the present application
  • V-1 is a precipitation tank
  • V-2 is an oxidation tank
  • V-3 is a neutralization tank
  • V-4 is a crystallization tank
  • V-5 is a phase separator
  • V-6 is a deesterification tank
  • 7 is an extraction kettle
  • V-8 is an ester crystallization kettle
  • V-9 is a water crystallization kettle
  • E-1, E-2, E-3, and E-4 are plate and frame filter presses.
  • the idea of the present application is that in the prior art, in the purification process of sucralose-6-ethyl ester, there are defects such as high energy consumption, low efficiency, a large amount of waste liquid, difficult waste liquid treatment, and low economic value. , and the technical defect of low yield of sucralose-6-ethyl ester, a method of converting sucralose diester and tetracralose-6-ester in chlorination reaction neutralization solution into sucralose- 6-ester, thereby increasing the yield of the target product.
  • Fig. 1 shows a schematic flowchart of a method for purifying sucralose-6-ester according to an embodiment of the present application. It can be seen from Fig. 1 that the present application includes at least step S110 to step S130.
  • Concentration step S110 Concentrate the mother liquor to be purified to remove the organic solvent, and after the concentration is completed, add water to it to form an aqueous solution to be purified; wherein, the mother liquor to be purified is prepared by neutralizing sucralose through esterification and chlorination The reaction solution of sucralose-6-ester was obtained.
  • the mother liquor to be purified in this application refers to the chlorination reaction solution of sucrose-6-ester, that is, the reactant mixed solution obtained by the chlorination reaction of sucrose-6-carboxylate and chlorination reagent. Further, the reagent can be used It is adjusted to be neutral, and it is called neutralizing solution for chlorination reaction.
  • This application is applicable to the reaction solution produced in the chlorination reaction stage in the preparation of sucralose by various methods in the prior art, such as single-group protection method, multi-group protection method, etc., for the chlorination reaction of sucrose-6-carboxylate
  • the source of the liquid is not limited in the present application, and it may be the reaction liquid produced in the chlorination reaction stage in the preparation of sucralose in the laboratory or in industrial production.
  • sucrose-6-carboxylate chlorination reaction solution generally adopts sodium hydroxide, ammonia water or directly adopts ammonia gas, but the product sucralose-6-carboxylate is alkaline
  • the solution not only can cause the hydrolysis reaction of sucralose-6-carboxylate, cause generation by-product, reduce the productive rate of sucralose-6-carboxylate; And process complexity, high energy consumption, low efficiency, A large amount of waste liquid is produced, and the economic value is small.
  • the mother liquor to be purified is concentrated to remove the organic solvent, and after the concentration is completed, water is added therein to form an aqueous solution to be purified.
  • Concentration can use any one of the existing technologies, such as distillation technology.
  • part of the water and organic impurities such as DMF and trichloroethane, can be evaporated, and this part of the distillate can be used as a solvent. Recycle.
  • the viscosity will be relatively large. In order to facilitate subsequent processing, it is best to configure it as an aqueous solution. Specifically, add water to the concentrated mother liquor to be purified, and stir evenly to form an aqueous solution to be purified.
  • Oxidation step S120 adding an oxidizing agent and a decolorizing agent to the aqueous solution to be purified in sequence to carry out an oxidative decolorization reaction, and then adding an alkali hydrolysis agent to the aqueous solution to be purified to oxidize the target impurity into sucralose-6-ester, and decolorize Colored impurities are removed; after a period of reaction, solid-liquid separation is carried out to obtain solid waste and the first filtrate.
  • the chlorination reaction neutralization liquid in addition to the target product sucralose-6-ethyl ester, the chlorination reaction neutralization liquid also contains more sucralose diester, tetrachloral sucralose- 6-ethyl ester, and to a lesser extent sucralose-6-ethyl ester and sucralose-6-ethyl ester. It has been found through research that the selective oxidation of sucralose diester and tetrachlorosucrose-6-ethyl ester can be carried out, and the two can be oxidized to the target product sucralose-6-ethyl ester. While removing impurities, it also improves The yield of the target product sucralose-6-ethyl ester was obtained.
  • a decolorizing agent can be added, and the oxidation reaction and decolorization reaction can be carried out simultaneously.
  • Sucralose-6-ethyl ester is prepared from sucrose. During the reaction, side reactions between sucrose, sucrose molecules Polymerization and coking will occur to form colored impurities, which can be removed by decolorizers.
  • an alkaline hydrolysis agent is added thereto.
  • an oxidizing agent on the one hand, the pH of the entire aqueous solution to be purified will change, specifically, an acidic environment will be formed; on the other hand, the target impurities sucralose diester and tetrachlorosucrose-6-ester and hypochlorite The corresponding complex intermediates will be formed.
  • alkaline substances such as ammonia to adjust its pH value to 8.5-10.5.
  • the chemical reaction formula for converting the impurities sucralose diester and tetrachlorosucrose-6-ester and hypochlorite into the target product sucralose-6-ester is as follows Shown:
  • the reaction of the oxidant to the sucralose diester in the presence of an alkali hydrolysis agent is to selectively remove the ester group to generate sucralose-6-ester;
  • the reaction is the selective removal of a chlorine atom to generate sucralose-6-ester.
  • solid-liquid separation is carried out to obtain solid waste and the first filtrate.
  • the decolorizing agent has been separated from the filtrate, and colored impurities are adsorbed in the decolorizing agent, the regeneration of the decolorizing agent and waste treatment can be carried out, and the obtained filtrate is recorded as the first filtrate.
  • crystallization step S130 after adjusting the first filtrate to neutrality, adding an extractant, performing extraction and crystallization at the same time, to obtain a crude product of sucralose-6-ester and a second filtrate.
  • neutral is not the condition that the pH value is absolutely equal to 7, and it can be considered as neutral when the pH value is around 7, for example, the pH value is in the range of 6-8.
  • an extractant is added, that is, crystallized while extracting.
  • the extractant is mainly to extract the organic esters that cannot be converted into the target product, mainly sucralose-6-ester and sucralose- 6-Ester. If extraction is carried out before crystallization, the extractant will also take out part of the target product sucralose-6-ester, which will affect the yield of sucralose-6-ester.
  • the present application processes the chlorination reaction neutralization solution of sucralose-6-ester by combining oxidizing agent and alkaline hydrolysis agent to remove the impurity sucralose diester therein. and tetrachloralose-6-ester is converted into the target product sucralose-6-ester, while effectively removing the impurity content, the yield of the target product is greatly improved; and the overall treatment process is simple and the economic cost is low,
  • the utility model has strong practicability; and can significantly reduce the COD (chemical oxygen demand) content of the wastewater, relieve the pressure of the subsequent wastewater treatment, and has extremely high application and economic value.
  • the method further includes: a filtrate recovery step: layering the second filtrate to obtain a first organic phase and a first aqueous phase, and evaporating the first organic phase to remove the extractant,
  • the sugar residue is obtained, dissolved in water, and separated from solid and liquid to obtain an aqueous solution of sugar residue; the aqueous solution of sugar residue is mixed with the first water phase, and an extractant is added for extraction, and the second organic phase obtained by extraction is recovered to the crystallization step. in the first filtrate.
  • the second filtrate can be layered and divided into the first organic phase and the first water phase.
  • Most of the three filtered sucrose-6-esters are dissolved in the water phase, and a small part is distributed in the organic phase.
  • the first The organic phase is evaporated to remove the extractant, the extractant can be recycled, and the evaporated organic phase forms sugar residue, which is a relatively viscous but still fluid mixture, which contains a small amount of water, DMF, trichloroethane, the target product sucralose-6-ester, organic ester impurities similar in structure to sucralose-6-ester, and some insoluble substances, etc.
  • the method further includes: a refining step: dissolving the obtained crude sucralose-6-ester in an extractant, performing first crystallization and separation, and obtaining an intermediate crystal and a third filtrate ; Dissolve the obtained intermediate crystal in water, carry out the second crystallization and separation, and obtain the refined product of sucralose-6-ester and the fourth filtrate.
  • the obtained sucralose-6-ester has a lower purity, and the sucralose-6-ester with higher purity can be obtained by recrystallization.
  • This application recommends a method of combining extraction crystallization with water crystallization. Specifically, the obtained crude sucralose-6-ester product is first dissolved in the extractant, and the first crystallization is performed. After crystallization, solid-liquid separation is carried out. Obtain intermediate crystals and a third filtrate; then dissolve the obtained intermediate crystals in water for a second crystallization, and perform solid-liquid separation after crystallization to obtain a refined product of sucralose-6-ester and a fourth filtrate.
  • the solubility of sucralose-6-ester in the extractant is greater than that in water, so the purity of sucralose-6-ester can be significantly improved by extraction and crystallization, and then the purity of sucralose-6-ester can be further improved by water crystallization The purity can also maintain the yield of sucralose-6-ester. Through the recrystallization of the crude product of the sucralose-6-ester, the refined product of the sucralose-6-ester with high purity is obtained.
  • the method further includes: recovering the third filtrate into the second filtrate that will enter the filtrate recovery step; recovering the fourth filtrate into the mother liquor to be purified that will enter the concentration step.
  • sucralose-6-ester in the extractant is relatively large, part of sucralose-6-ester still remains in the third filtrate, so it is necessary to reclaim it, and the third filtrate can be directly Enter the second filtrate in the filtrate recovery step, and extract and recover together with the second filtrate.
  • the fourth filtrate is usually called the water crystallization mother liquor.
  • the water crystallization mother liquor is an aqueous solution, it can be directly recycled to the incoming In the mother liquor to be purified in the concentration step.
  • the whole treatment process forms a closed loop, and the filtrate that may contain the target product is recovered, which greatly simplifies the treatment process and avoids the target product
  • the loss of sucralose-6-ester increases the yield of sucralose-6-ester.
  • the conditions for dissolving the sugar residue are not limited, as long as the sugar residue is completely dissolved; in other embodiments of the application, the dissolution temperature of the sugar residue can be set to The temperature is 40-70°C, and the dissolution time is set at 0.5-2 hours. Under this condition, the soluble part in the sugar residue can be completely dissolved.
  • the ratio of the mass of water added to the mass of the first organic phase is 0.5 to 2:1. If the mass of water added is less than 0.5 times the mass of the first organic phase, the amount of water added is too high. If the amount of water added is less than 2.0 times the mass of the first organic phase, it is difficult to dissolve the sugar residue. If the amount of water added is too much, it is not conducive to the subsequent extraction and crystallization.
  • the ratio of the volumetric usage of the extractant to the total volume of the sugar residue aqueous solution and the first aqueous phase is 0.1 ⁇ 1:1. If the volumetric dosage of the extractant is less than 0.1 times of the total volume of the sugar residue aqueous solution and the first aqueous phase, good extraction effect cannot be achieved; if the volumetric dosage of the extractant is greater than the total volume of the sugar residue aqueous solution and the first aqueous phase If the volume is doubled, the extraction effect cannot be further improved, and the extraction agent is wasted, and other beneficial effects cannot be brought.
  • the conditions in the refining step are not limited, as long as the sucralose-6-ester can be crystallized out.
  • the mass ratio of the amount of extractant to the crude product of sucralose-6-ester is 2 to 5:1; the crystallization temperature of the first crystallization is -5 ⁇ 10°C, the crystallization time is 0.5 ⁇ 3h; under the above conditions, a relatively ideal crystallization effect can be achieved.
  • the ratio of the mass of water to the mass of the intermediate crystal is 2-5:1; the crystallization temperature of the second crystallization is 0-30°C, and the crystallization time is 1-5h; under the above conditions, it can reach Ideal crystallization effect.
  • the conditions for concentrating the aqueous solution to be purified are not limited.
  • the concentrating temperature is 60-80° C.
  • the vacuum degree is -0.1 ⁇ -0.05Mpa.
  • the configuration volume of the aqueous solution to be purified is 0.5 to 1 times the volume of the mother liquor to be purified, that is to say, the volume of the aqueous solution to be purified is preset in advance, no matter how much liquid is evaporated from the mother liquor to be purified in the concentration step, The volume of the mother liquor to be purified is replenished to the configured volume of the aqueous solution to be purified by adding water, so that ideal extraction and crystallization effects can be achieved.
  • the oxidants were screened.
  • the oxidants were screened, it was found that when two conventional oxidants, hydrogen peroxide and ozone, were used for oxidation, if the amount of addition was unreasonably controlled, it would easily lead to the target product sucralose-6 - Oxidation of ethyl esters.
  • the addition of hydrogen peroxide it is easy to form peroxides in the system. When there are many peroxides and the stirring and cooling cannot be guaranteed, the danger of explosion is very likely to occur.
  • the inventors have found that when the oxidizing agent is one of sodium hypochlorite, sodium chlorate and calcium hypochlorite, the selective oxidation is better, especially sodium hypochlorite can achieve the most ideal selective oxidation effect, that is Able to oxidize sucralose diester and tetrachlorosucralose-6-ester to sucralose-6-ester and further oxidize sucralose-6-ester. And the inventor also found that when the amount of the oxidizing agent is 1-1.5 times the total mass of sucralose diester and tetrachlorosucrose-6-ester in the mother liquor to be purified, a more ideal effect can be achieved.
  • the type and amount of the decolorizing agent are not limited.
  • the decolorizing agent is one or more of activated carbon, attapulgite, diatomaceous earth and activated clay.
  • the decolorizing agent is activated carbon.
  • the above-mentioned decolorizing agents are all solid decolorizing agents, which can well adsorb the colored impurities formed by the polymerization of sucrose.
  • the amount of the decolorizing agent is not limited, and in other embodiments, the amount of the decolorizing agent is 0.05-0.2 wt% of the aqueous solution to be purified. Since the content of colored impurities is relatively small, from an economic point of view, it is recommended that the amount of the decolorizing agent be 0.05-0.2 wt% of the aqueous solution to be purified.
  • the temperature and time of the oxidative decolorization reaction are not limited, and the scope of the oxidation reaction in the prior art can be referred to to ensure that the reaction is complete; in other embodiments, the temperature of the oxidative decolorization reaction is 40-60°C, the reaction time is 1-4h; if the reaction temperature is lower than 40°C, the reaction time is shorter than 1h, the reaction conditions are relatively mild, and the problem of incomplete oxidation reaction is likely to occur; if the reaction temperature is higher than 60°C, the reaction time is longer than 4h , it is possible to overreact and even oxidize the sucralose-6-ester together.
  • alkaline hydrolysis agent there is no limitation to the type of alkaline hydrolysis agent, and alkaline substances can be used.
  • the alkaline hydrolysis agent is ammonia water or NaOH.
  • the alkaline hydrolysis agent For ammonia.
  • the amount of alkaline hydrolysis agent is not limited, as long as it reaches an alkaline environment, in other embodiments, the amount of alkaline hydrolysis agent is used to adjust the pH value of the aqueous solution to be purified to 8.5-10.5 as the benchmark.
  • the acidic substance is a common reagent for adjusting pH, such as dilute hydrochloric acid or dilute sulfuric acid.
  • dilute hydrochloric acid can be used.
  • the type and amount of the extractant there is no limitation on the type and amount of the extractant, as long as it can effectively dissolve monochlorosucrose-6-ester, dichlorosucrose-6-ester and other esters.
  • the extractant is one or a mixture of methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and isobutyl acetate. In some embodiments, ethyl acetate.
  • the target product sucralose-6-ester as well as impurities monochlorosucrose-6-ester, dichlorosucrose-6-ester, sucralose diester and tetrachlorosucrose-6-ester can be dissolved in The above-mentioned esters and water, but the solubility in the extractant is greater than the solubility in water, therefore, part of the organic ester impurities in the target product can be extracted from the target product to improve the target product sucralose-6-ester purity. It should be noted here that during the extraction process, a very small part of the target product sucralose-6-ester will be taken away by the extractant.
  • the amount of extractant is not limited, as long as it meets the extraction requirements, in other embodiments, for economic considerations, the ratio of the volume of extractant to the volume of the aqueous solution to be purified is 1:1 ⁇ 3.
  • sucralose-6-ester is an intermediate for the preparation of sucralose. Due to the high requirements for the purity of the final product sucralose, sucralose-6-ester is required The ester has a relatively high purity. Therefore, in this application, crystallization is performed while extracting to remove organic ester impurities similar in structure to the sucralose-6-ester.
  • the crystallization conditions there are no restrictions on the crystallization conditions, as long as the sucralose-6-ester can be effectively crystallized.
  • the extraction and crystallization are considered comprehensively and the screening In the crystallization step, the crystallization temperature of crystallization is -10-10°C, and the crystallization time is 6-12h. Within this range of conditions, the impurities can be effectively removed by extraction, and the sucralose-6-ester can be achieved in a relatively ideal yield without causing much loss to the sucralose-6-ester.
  • this purifying device 200 comprises:
  • Desolvation kettle V-1 oxidation kettle V-2; neutralization kettle V-3; crystallization kettle V-4; phase separator V-5; deesterification kettle V-6; extraction kettle V-7; ester crystallization kettle V -8; water crystallization kettle V-9, and plate and frame filter press E-1, E-2, E-3, E-4.
  • the outlet of the desolventization kettle V-1 is connected to the inlet of the oxidation kettle V-2; the outlet of the oxidation kettle V-2 is connected to the inlet of the neutralization kettle V-3, and the outlet of the neutralization kettle V-3 is connected to the plate and frame filter press
  • the inlet of E-1; the liquid outlet of the plate and frame filter press E-1 is connected to the inlet of the crystallization kettle V-4; the outlet of the crystallization kettle V-4 is connected to the inlet of the plate and frame filter press E-2; the plate and frame filter press
  • the solid substance outlet of E-2 is connected to the ester crystallization kettle V-8; the outlet of the ester crystallization kettle V-8 is connected to the inlet of the plate and frame filter press E-3; the solid substance outlet of the plate and frame filter press E-3 is connected to the water crystallization Kettle V-9; the outlet of water crystallization kettle V-9 is connected to plate and frame filter press E-4; the outlet of liquid material of plate and frame filter press E-2 is connected to phase separator V
  • the precipitation reactor V-1 can be an evaporating reactor, and a vacuum pump can be installed if necessary; or delete.
  • the chlorination reaction neutralization solution that is, the mother liquor to be purified
  • the desolventizer V-1 to concentrate, so as to remove most of the solvent DMF and trichloroethane, and then add pure water (and/or water crystallization mother liquor) to produce Aqueous solution to be purified.
  • oxidizing agent and decolorizer in sequence, and after reacting for a period of time under certain conditions, add alkaline hydrolysis agent until the pH of the aqueous solution to be purified reaches the preset value, such as 8.5 to 10.5, and continue to maintain the reaction a period of time.
  • the upper phase is the organic ester phase (second organic phase), and the second organic phase is sent to the crystallization tank V-3 to participate in crystallization, and the lower phase is the second organic phase.
  • the water phase, the second water phase is treated as high-salt wastewater.
  • the crude sucralose-6-ethyl ester separated from the plate and frame filter press E-2 is input into the ester crystallization kettle V-8, and an organic ester extractant is added for ester crystallization. After the crystallization is completed, it is sent to the plate and frame filter press E- 3; Obtain the crude ester crystallization (intermediate crystal) after being filtered by a filter press, send it into the water crystallization kettle V-9, add pure water into the water crystallization kettle V-9, and send it into the plate and frame filter press E- after crystallization 4 Separation by pressure filtration to obtain the fine sucralose-6-ethyl ester and the fourth filtrate, the fourth filtrate is the mother liquor of water crystallization, which can be sent to the precipitation tank V-1 for preparing the aqueous solution to be purified.
  • the mother liquor to be purified also known as the chlorination reaction neutralization liquor
  • the mother liquor to be purified is the chlorination liquor produced in the chlorination section in the production of sucralose, neutralized with ammonia water, and then adjusted to pH 6-8 with hydrochloric acid, in which the target group Divided into sucralose-6-ethyl ester, the contents of sucralose diester and tetracralose-6-ethyl ester in the components to be oxidized are obtained by liquid chromatography detection, and the other embodiments or comparative examples are the same, and will not be repeated one by one. repeat.
  • the concentration temperature is 80°C, vacuum degree -0.05Mpa, after the concentration is completed, add water crystallization mother liquor and pure water to make a concentrated aqueous solution, the volume is 4.9m 3 ;
  • the concentrated aqueous solution is input into the oxidation kettle V-2, and the oxidant sodium hypochlorite 78.46kg (based on the volume of the neutralizing solution) and 3.5kg of the decolorizing agent activated carbon (based on the volume of the neutralizing solution) are added successively, reacted at 40°C for 4h, and the reaction ends
  • press the material into the neutralization tank V-3 add ammonia water, adjust the pH of the system to 8.5, and then add dilute sulfuric acid to adjust the pH to 8.
  • the material enters the plate and frame filter press E-1 for pressure filtration Separation; the separated solid is treated as solid waste, and the filtrate enters crystallization tank V-4; ethyl acetate and ester phase extract are added to the crystallization tank to mix and crystallize with the filtrate, and the total volume of ethyl acetate and ester phase extract is the volume of the filtrate 1.5 times of that, the crystallization temperature is 0°C, and the crystallization time is 12h.
  • the material was input into the plate and frame filter press E-2 for pressure filtration and separation; the separated solid was crude sucralose-6-ethyl ester, and the yield and purity of the obtained crude product were shown in Table 2.
  • the concentration temperature is 85°C
  • the vacuum degree is -0.07Mpa
  • water crystallization mother liquor and pure water to make a concentrated aqueous solution with a volume of 3.5m 3
  • the concentrated aqueous solution is input into the oxidation kettle V-2, and the oxidant sodium hypochlorite 56.04kg (based on the volume of the neutralizing solution) and 2.5kg of decolorizing agent activated carbon (based on the volume of the neutralizing solution) are added successively, and reacted at 45°C for 3.5h, and the reaction
  • the material enters the plate and frame filter press E-1 for pressure filtration and separation; the separated solid is treated as solid waste, the filtrate enters the neutralization tank V-3, and ammonia water is added to adjust the pH of the system to 9.5, and then dilute sulfuric acid is added to adjust When the pH is 7.5, after the adjustment is completed, the material is input
  • the concentration temperature is 60°C
  • the vacuum degree is -0.1Mpa
  • the concentration is completed, add the water crystallization mother liquor and pure water to make a concentrated aqueous solution with a volume of 0.5m 3
  • Concentrated aqueous solution is input oxidation still V-2, add oxidant sodium hypochlorite 19kg (based on neutralization liquid volume) and decolorizing agent gac 2kg (based on neutralization liquid volume) successively, react 1h at 60 °C, after reaction finishes, Press the material into the neutralization kettle V-3, add ammonia water, adjust the pH of the system to 10.5, then add hydrochloric acid, adjust the pH to 6.5, after the adjustment, the material enters the plate and frame filter press E-1 for pressure filtration and separation; separation The solid that goes out is treated as solid waste, and the filtrate enters the crystallization tank V-4; in the crystallization tank, methyl acetate and ester phase extract are added
  • the material is input into the plate and frame filter press E-2 for pressure filtration and separation; the separated solid is the crude product of sucralose-6-ethyl ester, and the filtrate enters the phase separator V-5; from the upper end of the phase separator, the organic
  • the ester phase enters the deesterification kettle V-6, evaporates and removes the organic ester, then adds water to dissolve the sugar residue, the amount of water added is 0.5 times the volume of the ester, the dissolution temperature is 70°C, and the time is 0.5h.
  • the aqueous solution is input into the extraction kettle V-7, and the insoluble sugar slag is treated as waste; the water phase is separated from the lower end of the phase separator into the extraction kettle V-7, and methyl acetate is added to it for extraction.
  • the plate and frame filter press E-4 for pressure filtration and separation. After the separation, the fine sucralose-6-ethyl ester is obtained, and the water crystal mother liquor is sent to the concentration kettle V-1 to prepare a concentrated aqueous solution.
  • Table 6 The obtained crude product yield and purity are shown in Table 6.
  • the yield is calculated based on the initial content of sucralose-6-ethyl ester in the neutralization solution of the chlorination reaction (other examples are the same).
  • the material is input into the plate and frame filter press E-2 for pressure filtration and separation; the separated solid is the crude product of sucralose-6-ethyl ester, and the filtrate enters the phase separator V-5; from the upper end of the phase separator, the organic
  • the ester phase enters the deesterification kettle V-6, evaporates and removes the organic ester, then adds water to dissolve the sugar residue, the amount of water added is twice the volume of the ester, the dissolution temperature is 40°C, and the time is 2 hours.
  • the aqueous solution is input into the extraction kettle V-7, and the insoluble sugar slag is treated as waste; the water phase is separated from the lower end of the phase separator into the extraction kettle V-7, and ethyl acetate is added to it for extraction.
  • the plate and frame filter press E-4 for pressure filtration and separation. After the separation, the fine sucralose-6-ethyl ester is obtained, and the water crystal mother liquor is sent to the concentration kettle V-1 to prepare a concentrated aqueous solution.
  • Table 8 The obtained crude product yield and purity are shown in Table 8.
  • the material enters the plate and frame filter press E-1 for pressure filtration Separation; the separated solid is treated as solid waste, and the filtrate enters the crystallization kettle V-4; in the crystallization kettle, add isobutyl acetate and ester phase extract and filtrate mixed crystallization, and the total volume of isobutyl acetate and ester phase extract is 1.5 times the volume of the filtrate, the crystallization temperature is 0°C, and the crystallization time is 8h.
  • the material is input into the plate and frame filter press E-2 for pressure filtration and separation; the separated solid is the crude product of sucralose-6-ethyl ester, and the filtrate enters the phase separator V-5; from the upper end of the phase separator, the organic
  • the ester phase enters the deesterification kettle V-6, evaporates and removes the organic ester, then adds water to dissolve the sugar residue, the amount of water added is 1.5 times the volume of the ester, the dissolution temperature is 50°C, and the time is 1.5h.
  • the aqueous solution is input into the extraction kettle V-7, and the insoluble sugar slag is treated as waste; the water phase is separated from the lower end of the phase separator into the extraction kettle V-7, and isobutyl acetate is added to it for extraction.
  • the plate and frame filter press E-4 for pressure filtration and separation. After the separation, the fine sucralose-6-ethyl ester is obtained, and the water crystal mother liquor is sent to the concentration kettle V-1 to prepare a concentrated aqueous solution.
  • Table 10 The obtained crude product yield and purity are shown in Table 10.
  • the concentration temperature is 65°C
  • the vacuum degree is -0.08Mpa
  • water crystallization mother liquor and pure water to make a concentrated aqueous solution with a volume of 3.2m 3 ;
  • the concentrated aqueous solution is input into the oxidation kettle V-2, and the oxidant sodium hypochlorite 61.62kg (based on the volume of the neutralizing solution) and 6.4kg of the decolorizing agent activated carbon (based on the volume of the neutralizing solution) are added successively, reacted at 60° C.
  • the material is input into the plate and frame filter press E-2 for pressure filtration and separation; the separated solid is the crude product of sucralose-6-ethyl ester, and the filtrate enters the phase separator V-5; from the upper end of the phase separator, the organic
  • the ester phase enters the deesterification kettle V-6, evaporates and removes the organic ester, then adds water to dissolve the sugar residue, the amount of water added is 0.5 times the volume of the ester, the dissolution temperature is 70°C, and the time is 0.5h.
  • the aqueous solution is input into the extraction kettle V-7, and the insoluble sugar residue is treated as waste; the water phase is separated from the lower end of the phase separator into the extraction kettle V-7, and butyl acetate is added to it for extraction.
  • the plate and frame filter press E-4 for pressure filtration and separation. After the separation, the fine sucralose-6-ethyl ester is obtained, and the water crystal mother liquor is sent to the concentration kettle V-1 to prepare a concentrated aqueous solution.
  • the crude product yield and purity obtained are shown in Table 12.
  • the material is input into the plate and frame filter press E-2 for pressure filtration and separation; the separated solid is the crude product of sucralose-6-ethyl ester, and the filtrate enters the phase separator V-5; from the upper end of the phase separator, the organic
  • the ester phase enters the deesterification kettle V-6, evaporates and removes the organic ester, then adds water to dissolve the sugar residue, the amount of water added is 1 times the volume of the ester, the dissolution temperature is 60°C, and the time is 1h.
  • the aqueous solution is input into the extraction kettle V-7, and the insoluble sugar slag is treated as waste; the water phase is separated from the lower end of the phase separator into the extraction kettle V-7, and isopropyl acetate is added to it for extraction.
  • the upper phase ester phase extract is sent to the crystallization tank V-3 to participate in crystallization, and the lower phase water phase is treated as high-salt wastewater; separated from the plate and frame filter press E-2
  • the crystallization time is 3h.
  • the plate and frame filter press E-4 for pressure filtration and separation. After the separation, the fine sucralose-6-ethyl ester is obtained, and the water crystal mother liquor is sent to the concentration kettle V-1 to prepare a concentrated aqueous solution.
  • the crude product yield and purity obtained are shown in Table 14.
  • the concentration temperature is 60°C
  • the vacuum degree is -0.1Mpa.
  • the concentrated aqueous solution is input into the oxidation kettle V-2, and the oxidant sodium hypochlorite 72.79kg (based on the volume of the neutralizing solution) and 6 kg of decolorizing agent activated carbon (based on the volume of the neutralizing solution) are added successively, and reacted at 50° C. for 3 hours.
  • the material is input into the plate and frame filter press E-2 for pressure filtration and separation; the separated solid is the crude product of sucralose-6-ethyl ester, and the filtrate enters the phase separator V-5; from the upper end of the phase separator, the organic
  • the ester phase enters the deesterification kettle V-6, evaporates and removes the organic ester, then adds water to dissolve the sugar residue, the amount of water added is 1.5 times the volume of the ester, the dissolution temperature is 50°C, and the time is 1.5h.
  • the aqueous solution is input into the extraction kettle V-7, and the insoluble sugar residue is treated as waste; the water phase is separated from the lower end of the phase separator into the extraction kettle V-7, and propyl acetate is added to it for extraction.
  • the plate and frame filter press E-4 for pressure filtration and separation. After the separation, the fine sucralose-6-ethyl ester is obtained, and the water crystal mother liquor is sent to the concentration kettle V-1 to prepare a concentrated aqueous solution.
  • the obtained crude product yield and purity are shown in Table 16.
  • the concentration temperature is 80°C, vacuum degree -0.05Mpa, after the concentration is completed, add water crystallization mother liquor and pure water to make a concentrated aqueous solution, the volume is 4.9m 3 ;
  • the concentrated aqueous solution is input into the oxidation kettle V-2, and the oxidant sodium hypochlorite 78.46kg (based on the volume of the neutralizing solution) and 3.5kg of the decolorizing agent activated carbon (based on the volume of the neutralizing solution) are added successively, reacted at 40°C for 4h, and the reaction ends
  • press the material into the neutralization tank V-3 add ammonia water, adjust the pH of the system to 8.5, and then add dilute sulfuric acid to adjust the pH to 8.
  • the material enters the plate and frame filter press E-1 for pressure filtration Separation; the separated solid is treated as solid waste, and the filtrate enters crystallization tank V-4; ethyl acetate and ester phase extract are added to the crystallization tank to mix and crystallize with the filtrate, and the total volume of ethyl acetate and ester phase extract is the volume of the filtrate 1.5 times of that, the crystallization temperature is 0°C, and the crystallization time is 12h.
  • the material is input into the plate and frame filter press E-2 for pressure filtration and separation; the separated solid is the crude product of sucralose-6-ethyl ester, and the filtrate enters the phase separator V-5; from the upper end of the phase separator, the organic
  • the ester phase enters the deesterification kettle V-6, evaporates and removes the organic ester, then adds water to dissolve the sugar residue, the amount of water added is twice the volume of the ester, the dissolution temperature is 40°C, and the time is 2 hours.
  • the aqueous solution is input into the extraction kettle V-7, and the insoluble sugar slag is treated as waste; the water phase is separated from the lower end of the phase separator into the extraction kettle V-7, and ethyl acetate is added to it for extraction.
  • the plate and frame filter press E-4 for pressure filtration and separation. After the separation, the fine sucralose-6-ethyl ester is obtained, and the water crystal mother liquor is sent to the concentration kettle V-1 to prepare a concentrated aqueous solution.
  • the crude product yield and purity obtained are shown in Table 18.
  • the concentration temperature is 60°C
  • the vacuum degree is -0.1Mpa
  • the concentration is completed, add water crystallization mother liquor and pure water to make a concentrated aqueous solution, the volume is the original chlorination 1 times the volume of the reaction neutralization solution; the concentrated aqueous solution is input into the oxidation kettle V-2.
  • the material is input into the plate and frame filter press E-2 for pressure filtration and separation; the separated solid is the crude product of sucralose-6-ethyl ester, and the filtrate enters the phase separator V-5; from the upper end of the phase separator, the organic
  • the ester phase enters the deesterification kettle V-6, evaporates and removes the organic ester, then dissolves the sugar residue with water, the amount of water added is 1 times the volume of the ester, the dissolution temperature is 60°C, and the time is 2h.
  • the aqueous solution is input into the extraction kettle V-7, and the insoluble sugar slag is treated as waste; the water phase is separated from the lower end of the phase separator into the extraction kettle V-7, and ethyl acetate is added to it for extraction.
  • the plate and frame filter press E-4 for pressure filtration and separation. After the separation, the fine sucralose-6-ethyl ester is obtained, and the water crystal mother liquor is sent to the concentration kettle V-1 to prepare a concentrated aqueous solution.
  • Table 20 The obtained crude product yield and purity are shown in Table 20.
  • this comparative example selects the same sample as in Example 10, and performs the same operation to purify sucralose-6-ethyl ester, different The difference is that an oxidizing agent was added in Example 10, and no oxidizing agent was added in Comparative Example 1.
  • the components of neutralizing solution for chlorination reaction are shown in Table 21.
  • the concentration temperature is 60°C
  • the vacuum degree is -0.1Mpa
  • the concentration is completed, add water crystallization mother liquor and pure water to make a concentrated aqueous solution, the volume is the original chlorination 1 times the volume of the reaction neutralization solution; the concentrated aqueous solution is input into the oxidation kettle V-2.
  • Method 1 Add 55.57 kg of oxidant sodium hypochlorite (based on the volume of neutralizing liquid) and 4 kg of decolorizing agent activated carbon (based on the volume of neutralizing liquid) in sequence;
  • Method 2 add 4 kg of decolorizing agent activated carbon (based on the volume of neutralizing liquid) , react at 60°C for 2 hours, after the reaction, press the material into the neutralization tank V-3, add ammonia water, adjust the pH of the system to 9.5, then add hydrochloric acid, adjust the pH to 7.5, after the adjustment, the material enters the plate frame Filter press E-1 is separated by pressure filtration; the separated solid is treated as solid waste, and the filtrate enters the crystallization kettle V-4; ethyl acetate and ester phase extract are added to the crystallization kettle to mix and crystallize with the filtrate, ethyl acetate and ester The total volume of the phase extract is 2.5 times the volume of the filtrate, the crystallization temperature is -5°C, and the crystall
  • the material is input into the plate and frame filter press E-2 for pressure filtration and separation; the separated solid is the crude product of sucralose-6-ethyl ester, and the filtrate enters the phase separator V-5; from the upper end of the phase separator, the organic
  • the ester phase enters the deesterification kettle V-6, evaporates and removes the organic ester, then dissolves the sugar residue with water, the amount of water added is 1 times the volume of the ester, the dissolution temperature is 60°C, and the time is 2 hours.
  • the aqueous solution is input into the extraction kettle V-7, and the insoluble sugar slag is treated as waste; the water phase is separated from the lower end of the phase separator into the extraction kettle V-7, and ethyl acetate is added to it for extraction.
  • the plate and frame filter press E-4 for pressure filtration and separation. After the separation, the fine sucralose-6-ethyl ester is obtained, and the water crystal mother liquor is sent to the concentration kettle V-1 to prepare a concentrated aqueous solution.
  • the crude product yield and purity obtained are shown in Table 22.
  • a method for purifying sucralose-6-ethyl ester of the present application by adding an oxidizing agent during the purification process, the two impurities sucralose diester and tetrachlorosucralose-6-ethyl ester are oxidized, Converted to the target product sucralose-6-ethyl ester, thereby increasing the overall yield of sucralose-6-ethyl ester, on the one hand, increasing the production capacity of sucralose-6-ethyl ester, and on the other hand, reducing high-salt wastewater COD content, ease the pressure of subsequent biochemical treatment.
  • this method simplifies operation, shortens the process, realizes cost reduction and efficiency increase, and can create greater economic benefits.
  • connection should be understood in a broad sense, for example, it can be a fixed connection or a detachable connection. Connected, or integrally connected; it may be mechanically connected or electrically connected; it may be directly connected or indirectly connected through an intermediary, and it may be the internal communication of two components. Those of ordinary skill in the art can understand the specific meanings of the above terms in this application in specific situations.

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Abstract

本申请提供了一种三氯蔗糖-6-酯的提纯方法，包括：浓缩步骤：将待提纯母液进行浓缩，以脱除有机溶剂，浓缩完成后，向其中加入水，形成待提纯水溶液；氧化步骤：向待提纯水溶液中依次加入氧化剂和脱色剂，进行氧化脱色反应，再加入碱解剂，以将目标杂质氧化为三氯蔗糖-6-酯，以及脱除有色杂质；反应一段时间后，进行固液分离，得到固体废弃物和第一滤液；和结晶步骤：将第一滤液调解至中性后，加入萃取剂，同时进行萃取和结晶，得到三氯蔗糖-6-酯粗产品和第二滤液。本申请在有效去除了杂质含量的同时，极大程度上提高目的产物的收率；且整体处理工艺简单、经济成本低，实用性强；且能够显著降低废水的COD含量。

Description

三氯蔗糖-6-酯的提纯方法 技术领域
本发明属于精细化工技术领域，具体涉及一种三氯蔗糖-6-酯的提纯方法。
发明背景
三氯蔗糖-6-酯是合成三氯蔗糖的主要中间体之一，可由蔗糖经酯化、氯化、脱酯基得来。传统的绿色氯化工艺是蔗糖-6-酯在N,N-二甲基甲酰胺(DMF)与三氯乙烷做溶剂的情况下，经氯化亚砜高温氯化制得。由于氯化试剂氯化亚砜使用量远高于理论氯化的等摩尔使用量，且氯化温度较高(＞100℃)，因此所得的氯化液杂质较多。以酯化剂为乙酸为例，除目标产物三滤蔗糖-6-乙酯外，还存在大量的三氯蔗糖双酯、四氯蔗糖-6-乙酯、少量的一氯蔗糖-6-乙酯和二氯蔗糖-6-乙酯等。为了制备纯净的三氯蔗糖，工业上常需要将三氯蔗糖-6-乙酯经多步提纯制备出三氯蔗糖-6-乙酯精品，然后再经甲醇/甲醇钠水解，提纯后得到三氯蔗糖。
现有技术中，关于三氯蔗糖-6-乙酯的提纯方法，均属于常规提纯方式。如中国专利CN110563780，该专利采用有机碱做中和剂，浓缩配置成水溶液后，采用诸如乙酸乙酯、乙酸丁酯、氯甲烷、氯苯等溶剂进行萃取结晶。一方面碱性较弱的长链有机碱并不适合进行氯化液的中和，另一方面采用二氯甲烷、三氯甲烷、氯苯或甲基叔丁基醚进行萃取，由于三氯蔗糖-6-乙酯在以上溶剂中的溶解度较低，萃取效率低下，因此应用前景较小。
又如中国专利CN108191927，该专利采用有机溶剂Ⅰ溶解析晶，再用有机溶剂Ⅱ溶解析出晶体，加浓稀硫酸碳化处理。在第一步析晶过程中，由于已浓缩的粘稠糖液包覆性很强，单纯的加入有机溶剂Ⅰ无法高效地将三氯蔗糖-6-乙酯溶解，且采用浓稀硫酸外加有机溶剂Ⅱ对糖渣进行碳化处理，对于糖渣中残余的三氯蔗糖-6-乙酯，以及可以转化为三氯蔗糖-6-乙酯的杂质，均是一种浪费，这将对该工艺在经济上的价值有影响。
专利CN103012509通过添加无机盐的方式进行盐析提纯三氯蔗糖-6-乙酯，添加量为母液的6～12wt％，暂且不论此种工艺是否能将三氯蔗糖-6-乙酯完全从氯代反应中和液中取出，后续需要处理的盐含量极高的高盐废水，严重影响该专利的实用价值。
此外，还有如中国专利CN101941995，以及中国专利CN106589013等中报道的关于三氯蔗糖-6-乙酯的提纯方式，均为常规的萃取、结晶。
综上所述，现有技术中，对于三氯蔗糖-6-乙酯的提纯均为传统的分离氯化液中的杂质的思路，这种方式存在着耗能高、效率低下、产生大量废液、经济价值小等缺陷，且三氯蔗糖-6-乙酯的收率低下，亟需一种三氯蔗糖-6-酯的提纯方法以解决上述问题。
发明内容
鉴于现有技术，对三氯蔗糖-6-乙酯提纯工艺中，存在着耗能高、效率低下、产生大量废液、经济价值小等缺陷，且三氯蔗糖-6-乙酯的收率低下的问题，提出了本申请以便提供一种克服上述问题或者至少部分地解决上述问题的一种三氯蔗糖-6-酯的提纯方法。
根据本申请的第一方面，提供了一种三氯蔗糖-6-酯的提纯方法，包括：
浓缩步骤：将待提纯母液进行浓缩，以脱除有机溶剂，浓缩完成后，向其中加入水，形成待提纯水溶液；其中，待提纯母液通过中和三氯蔗糖经酯化、氯代反应制备三氯蔗糖-6-酯的反应液得来；
氧化步骤：向待提纯水溶液中依次加入氧化剂和脱色剂，进行氧化脱色反应，然后向所述待提纯水溶液中加入碱解剂，以将目标杂质氧化为三氯蔗糖-6-酯，以及脱除有色杂质；反应一段时间后，进行固液分离，得到固体废弃物和第一滤液；和
结晶步骤：将第一滤液调解至中性后，加入萃取剂，同时进行萃取和结晶，得到三氯蔗糖-6-酯粗产品和第二滤液。
可选的，该方法还包括：
滤液回收步骤：将第二滤液分层，得到第一有机相和第一水相，将第一有机相进行蒸发，以脱除萃取剂，得到糖渣，加水溶解、固液分离后，得到糖渣水溶液；
将糖渣水溶液与第一水相混合，并加入萃取剂进行萃取，将萃取得到的第二有机相回收至要进入结晶步骤的第一滤液中。
可选的，在上述方法中，在滤液回收步骤中，水的添加质量与第一有机相的质量的比为0.5～2:1，溶解的溶解温度为40～70℃，溶解时间为0.5～2h；
萃取剂的体积用量与糖渣水溶液与第一水相的总体积的比为0.1～1:1。
可选的，该方法还包括：
精制步骤：将得到的三氯蔗糖-6-酯粗产品溶解于萃取剂中，进行第一次结晶和分离，得到中间结晶体和第三滤液；
将得到的中间结晶体溶解于水中，进行第二次结晶和分离，得到三氯蔗糖-6-酯精制产品和第四滤液。
可选的，该方法还包括：
将第三滤液回收至要进入滤液回收步骤的第二滤液中；
将第四滤液回收至要进入浓缩步骤的待提纯母液中。
可选的，在上述方法中，在精制步骤中，萃取剂的质量用量与三氯蔗糖-6-酯粗产品的质量的比为2～5:1；第一次结晶的结晶温度为-5～10℃，结晶时间为0.5～3h；
水的质量用量与中间结晶体的质量的比为2～5:1；第二次结晶的结晶温度为0～30℃，结晶时间1～5h。
可选的，在上述方法中，在浓缩步骤中，浓缩的温度为60～80℃，真空度为-0.1～-0.05Mpa；
待提纯水溶液的配置体积为待提纯母液体积的0.5～1倍。
可选的，在上述方法中，在氧化步骤中，氧化剂为次氯酸钠、氯酸钠和次氯酸钙中的一种，优选为次氯酸钠；
氧化剂的用量为待提纯母液中目标杂质总质量的1～1.5倍。
可选的，在上述方法中，在氧化步骤中，脱色剂为活性炭、凹凸棒土、硅藻土和活性白土中的一种或几种，优选活性炭；
脱色剂的用量为待提纯水溶液的0.05～0.2wt％；
氧化脱色反应的温度为40～60℃，反应时间1～4h。
可选的，在上述方法中，在氧化步骤中，碱解剂为氨水或NaOH，优选氨水；
碱解剂的用量以将待提纯水溶液的pH值调节至8.5-10.5为基准。
可选的，在上述方法中，在结晶步骤中，将第一滤液调解至中性包括：
采用酸性物质将第一滤液的pH值调节至6.5-8.0；其中，酸性物质为稀盐酸或稀硫酸，优选稀盐酸。
可选的，在上述方法中，在结晶步骤中，萃取剂为乙酸甲酯、乙酸乙酯、乙酸丙酯、乙酸异丙酯、乙酸丁酯和乙酸异丁酯中的一种或几种，优选为乙酸乙酯；
萃取剂的体积用量与待提纯水溶液的体积的比为1:1～3；
结晶的温度为-10～10℃，结晶时间为6～12h。
本申请的有益效果在于，本申请通过氧化剂和碱解剂结合使用对制备三氯蔗糖-6-酯的氯代反应中和液进行处理，以将其中的杂质三氯蔗糖双酯及四氯蔗糖-6-酯转化为目标产物三氯蔗糖-6-酯，在有效去除了杂质含量的同时，极大程度上提高 目的产物的收率；且整体处理工艺简单、流畅，经济成本低，实用性强；所得三氯蔗糖-6-酯纯度较高，可以直接进行三氯蔗糖的生产活动；且能够显著降低废水的杂质含量，缓解了后续废水处理的压力，对环境友好度高，具有极高的应用和经济价值。
上述说明仅是本申请技术方案的概述，为了能够更清楚了解本申请的技术手段，而可依照说明书的内容予以实施，并且为了让本申请的上述和其它目的、特征和优点能够更明显易懂，以下特举本申请的具体实施方式。
附图简要说明
通过阅读下文优选实施方式的详细描述，各种其他的优点和益处对于本领域普通技术人员将变得清楚明了。附图仅用于示出优选实施方式的目的，而并不认为是对本申请的限制。而且在整个附图中，用相同的参考符号表示相同的部件。在附图中：
图1示出了根据本申请的一个实施例的三氯蔗糖-6-酯的提纯方法的流程示意图；
图2示出了根据本申请的一个实施例的三氯蔗糖-6-酯的提纯装置的结构示意图；
其中，V-1为脱溶釜；V-2为氧化釜；V-3为中和釜；V-4为结晶釜；V-5为分相器；V-6为脱酯釜；V-7为萃取釜；V-8为酯结晶釜；V-9为水结晶釜；E-1、E-2、E-3、E-4为板框压滤机。
实施本发明的方式
下面将更详细地描述本申请的示例性实施例。虽然显示了本申请的示例性实施例，然而应当理解，可以以各种形式实现本申请而不应被这里阐述的实施例所限制。相反，提供这些实施例是为了能够更透彻地理解本申请，并且能够将本申请的范围完整地传达给本领域的技术人员。
本申请的构思在于，针对现有技术中，对三氯蔗糖-6-乙酯提纯工艺中，存在着耗能高、效率低下、产生大量废液、废液处理难度大、经济价值小等缺陷，且三氯蔗糖-6-乙酯的收率低下的技术缺陷，提出了一种将氯代反应中和液中的三氯蔗糖双酯及四氯蔗糖-6-酯转化为三氯蔗糖-6-酯，从而提高目的产物的收率的方法。
图1示出了根据本申请的一个实施例的三氯蔗糖-6-酯的提纯方法的流程示意图，从图1可以看出，本申请至少包括步骤S110～步骤S130。
浓缩步骤S110：将待提纯母液进行浓缩，以脱除有机溶剂，浓缩完成后，向其中加入水，形成待提纯水溶液；其中，待提纯母液通过中和三氯蔗糖经酯化、氯代反应制备三氯蔗糖-6-酯的反应液得来。
本申请中的待提纯母液指的是蔗糖-6-酯的氯代反应液，即蔗糖-6-羧酸酯与氯化试剂进行氯代反应得到的反应物混合溶液，进一步的，可采用试剂调节为中性，称为氯代反应中和液。本申请适用于现有技术中各种方法制备三氯蔗糖中氯代反应阶段产生的反应液，如单基团保护法、多基团保护法等，对于蔗糖-6-羧酸酯氯代反应液的来源本申请不做限制，可为实验室或工业生产中的制备三氯蔗糖中氯代反应阶段产生的反应液。
由于在氯代反应过程中，使用了强的氯代试剂，如氯化亚砜和光气等，在氯代保温阶段温度高，会产生一系列的副产物，如一氯代蔗糖-6-羧酸酯、二氯代蔗糖-6-羧酸酯、四氯代蔗糖-6-羧酸酯、三氯蔗糖双酯等，还含有一些有机杂质如N,N-二甲基甲酰胺(DMF)和三氯乙烷，以及大量的水。目前，现有技术中，对蔗糖-6-羧酸酯氯代反应液的中和处理一般采用氢氧化钠、氨水或直接采用氨气，但产物三氯蔗糖-6-羧酸酯在碱性溶液中，不仅会引起三氯蔗糖-6-羧酸酯发生水解反应，导致生成副产物，降低了三氯蔗糖-6-羧酸酯的产率；而且工艺复杂、耗能高、效率低下、产生大量废液、经济价值小。
首先，将待提纯母液进行浓缩，以脱除有机溶剂，浓缩完成后，向其中加入水，形成待提纯水溶液。
浓缩可以采用现有技术中的任意一种，如蒸馏技术，在这个过程中，能够把部分的水，有机杂质，如DMF和三氯乙烷等蒸发出去，对这部分蒸出物可以做溶剂回收。
待提纯母液被浓缩后，粘度会比较大，为了方便后续处理，最好将其配置成水溶液，具体的，向浓缩后的待提纯母液中加入水，搅拌均匀，形成待提纯水溶液。
氧化步骤S120：向待提纯水溶液中依次加入氧化剂和脱色剂，进行氧化脱色反应，然后向所述待提纯水溶液中加入碱解剂，以将目标杂质氧化为三氯蔗糖-6-酯，以及脱除有色杂质；反应一段时间后，进行固液分离，得到固体废弃物和第一滤液。
申请人通过对氯代反应中和液成分分析发现，氯代反应中和液中除了含有目标 产物三氯蔗糖-6-乙酯外，还含有较多的三氯蔗糖双酯、四氯蔗糖-6-乙酯、以及较少的一氯蔗糖-6-乙酯和二氯蔗糖-6-乙酯。经研究发现，可以对三氯蔗糖双酯、四氯蔗糖-6-乙酯进行选择性氧化，将这二者氧化为目标产物三氯蔗糖-6-乙酯，在去除杂质的同时，也提高了目标产物三氯蔗糖-6-乙酯的收率。
在加入氧化剂后，可加入脱色剂，氧化反应和脱色反应可同时进行，三氯蔗糖-6-乙酯是采用蔗糖为原料制备的，在反应过程中，蔗糖之间会发生副反应，蔗糖分子会发生聚合焦化，形成有色的杂质，这些有色杂质，能够通过脱色剂去除。
在氧化脱色反应进行一段时间后，向其中加入碱解剂。由于加入氧化剂后，一方面，整个待提纯水溶液的酸碱度会发生变化，具体的，会形成酸性环境；另一方面，目标杂质三氯蔗糖双酯和四氯代蔗糖-6-酯与次氯酸根会形成相应的复合中间体。这时采用如氨水等碱性物质将其pH值调节至8.5-10.5，这是因为氧化剂与目标杂质三氯蔗糖双酯和四氯代蔗糖-6-酯形成的复合中间体需要碱性物质中和待脱除基团，才能形成目标产物三氯蔗糖-6-酯。
以次氯酸钠为氧化剂、氢氧化铵为碱解剂为例，杂质三氯蔗糖双酯和四氯代蔗糖-6-酯与次氯酸根转化为目标产物三氯蔗糖-6-酯的化学反应式如下所示：
Figure PCTCN2021104939-appb-000001
从化学反应式可以看出，氧化剂在碱解剂存在下对三氯蔗糖双酯的反应是选择性脱除酯基，生成三氯蔗糖-6-酯；氧化剂对四氯代蔗糖-6-酯的反应是选择性脱除一个氯原子，生成三氯蔗糖-6-酯。
反应一段时间后，进行固液分离，得到固体废弃物和第一滤液。如减压抽滤， 已将脱色剂与滤液分离，脱色剂中吸附有有色杂质，可以进行脱色剂再生和废弃物处理，所得滤液记为第一滤液。
和，结晶步骤S130：将第一滤液调解至中性后，加入萃取剂，同时进行萃取和结晶，得到三氯蔗糖-6-酯粗产品和第二滤液。
在待提纯水溶液中发生氧化脱色反应后，会影响其酸碱性，得到的第一滤液为碱性，在进行结晶之前，最好将其调节至中性。需要说明的是，在本申请中，所谓“中性”不是pH值绝对等于7的条件，在pH值为7左右均可认为是中性，如pH值在6-8的范围内。
在本申请中，在结晶时，加入萃取剂，即边萃取边结晶，萃取剂主要是为了将不能转化成目标产物的有机酯萃取出，主要是一氯蔗糖-6-酯和二氯蔗糖-6-酯。如果在结晶前进行萃取，萃取剂会将部分目标产物三氯蔗糖-6-酯也带出，影响三氯蔗糖-6-酯的收率。
结晶完成后，进行固液分离，得到三氯蔗糖-6-酯粗产品和滤液，该滤液记为第二滤液。
从图1所示的方法可以看出，本申请通过将氧化剂和碱解剂结合使用对三氯蔗糖-6-酯的氯代反应中和液进行处理，以将其中的杂质三氯蔗糖双酯及四氯蔗糖-6-酯转化为目标产物三氯蔗糖-6-酯，在有效去除了杂质含量的同时，极大程度上提高目的产物的收率；且整体处理工艺简单、经济成本低，实用性强；且能够显著降低废水的COD(化学需氧量)含量，缓解了后续废水处理的压力，具有极高的应用和经济价值。
在本申请的一些实施例中，该方法还包括：滤液回收步骤：将第二滤液分层，得到第一有机相和第一水相，将第一有机相进行蒸发，以脱除萃取剂，得到糖渣，加水溶解、固液分离后，得到糖渣水溶液；将糖渣水溶液与第一水相混合，并加入萃取剂进行萃取，将萃取得到的第二有机相回收至要进入结晶步骤的第一滤液中。
在第二滤液中，还有留存有一部分目标产物没有被结晶出，可以对这部分滤液进行回收再处理，以提高三氯蔗糖-6-酯的收率。
具体的，可将第二滤液进行分层，分为第一有机相和第一水相，三滤蔗糖-6-酯大部分溶解在水相中，少部分分布在有机相中，将第一有机相进行蒸发，脱除萃取剂，萃取剂可做回收处理，蒸发后的有机相形成糖渣，糖渣是比较粘稠的但仍然具有流动性的混合物，在该混合物中包含少量的水、DMF、三氯乙烷、目标产物三氯蔗糖-6-酯、与三氯蔗糖-6-酯结构类似的有机酯杂质，以及一些不溶物等。
加水溶解上述糖渣，可搅拌加速溶解，在溶解完成后，进行固液分离，不溶物做废弃物处理。糖渣水溶液与第一水相混合，然后加入萃取剂，萃取剂将溶解绝大部分的目标产物三氯蔗糖-6-酯、与三氯蔗糖-6-酯结构类似的有机酯杂质，进一步的，可以将这部分萃取液进行单独结晶，以获取目标产物三氯蔗糖-6-酯，也可以将这部分萃取液混入至要进入结晶步骤的第一滤液中，并与原始的第一滤液一起进行萃取和结晶，得到三氯蔗糖-6-酯。
在本申请的一些实施例中，该方法还包括：精制步骤：将得到的三氯蔗糖-6-酯粗产品溶解于萃取剂中，进行第一次结晶和分离，得到中间结晶体和第三滤液；将得到的中间结晶体溶解于水中，进行第二次结晶和分离，得到三氯蔗糖-6-酯精制产品和第四滤液。
经过一次结晶步骤，得到的三氯蔗糖-6-酯纯度较低，可以通过重结晶的方法获取纯度更高的三氯蔗糖-6-酯。
本申请推荐一种萃取结晶与水结晶结合的方法，具体的，先将得到的三氯蔗糖-6-酯粗产品溶解于萃取剂中，进行第一次结晶，结晶后，进行固液分离，得到中间结晶体和第三滤液；然后将得到的中间结晶体溶解于水中，进行第二次结晶，结晶后，进行固液分离，得到三氯蔗糖-6-酯精制产品和第四滤液。
三氯蔗糖-6-酯在萃取剂中的溶解度大于在水中的溶解度，因此通过萃取结晶能显著提高三氯蔗糖-6-酯的纯度，然后通过水结晶能够进一步提高三氯蔗糖-6-酯的纯度，还能够维持三氯蔗糖-6-酯的收率。通过对三氯蔗糖-6-酯粗产品的重结晶，得到了纯度很高的三氯蔗糖-6-酯精制产品。
在本申请的一些实施例中，该方法还包括：将第三滤液回收至要进入所述滤液回收步骤的第二滤液中；将第四滤液回收至要进入浓缩步骤的待提纯母液中。
由于三氯蔗糖-6-酯在萃取剂中的溶解度较大，因此，在第三滤液中仍然留存着部分三氯蔗糖-6-酯，因此有必要对其进行回收，可直接将第三滤液进入所述滤液回收步骤的第二滤液中，与第二滤液一起进行萃取回收。
第四滤液通常被称为水结晶母液，同理，其中也仍然留存着部分三氯蔗糖-6-酯，有必要对其进行回收，由于水结晶母液为水溶液，因此可以直接将其回收至进入浓缩步骤的待提纯母液中。
通过对第二滤液、第三滤液和第四滤液的回收，使得整个处理过程形成一个循环闭环，可能含有的目标产物的滤液均被回收，极大程度上简化了处理工艺，且避免了目标产物三氯蔗糖-6-酯的流失，提高了三氯蔗糖-6-酯的收率。
由于本申请涉及的蒸馏、萃取等过程均需要消耗时间和能量，且溶剂的加入也影响到结晶的效果，因此下述对提纯的各个步骤的条件进行了探索。
第二滤液的处理条件
在本申请的一些实施例中，在滤液回收步骤中，对糖渣溶解的条件不作限制，保障糖渣完全溶解即可；在本申请的另一些实施例中，糖渣溶解的溶解温度可设为40～70℃，溶解时间设为0.5～2h，在该条件下，糖渣中的可溶部分已经可以完全溶解完毕。
在本申请的一些实施例中，水的添加质量与第一有机相的质量的比为0.5～2:1，若水的添加质量小于第一有机相的质量的0.5倍，则水的添加量过少，糖渣溶解困难，若水的添加质量大于第一有机相的质量的2.0倍，则水的添加量过多，不利于后续的萃取和结晶。
在本申请的一些实施例中，萃取剂的体积用量与糖渣水溶液与第一水相的总体积的比为0.1～1:1。若萃取剂的体积用量小于糖渣水溶液与第一水相的总体积的0.1倍，则不能够起到很好的萃取效果；若萃取剂的体积用量大于糖渣水溶液与第一水相的总体积的1倍，已不能进一步提高萃取效果，且造成了萃取剂的浪费，也不能带来其他有益效果。
精制步骤的条件
在本申请的一些实施例中，对精制步骤中的条件不作限制，只要能够将三氯蔗糖-6-酯结晶析出即可。
在另一些实施例中，在萃取结晶过程中，萃取剂的质量用量与三氯蔗糖-6-酯粗产品的质量的比为2～5:1；第一次结晶的结晶温度为-5～10℃，结晶时间为0.5～3h；在上述条件下，能够达到比较理想的结晶效果。
在水结晶过程中，水的质量用量与中间结晶体的质量的比为2～5:1；第二次结晶的结晶温度为0～30℃，结晶时间1～5h；在上述条件下，能够达到比较理想的结晶效果。
浓缩步骤条件
在本申请的一些实施例中，对待提纯水溶液的浓缩条件不做限制，在另一些实施例中，考虑到经济和时间因素，在浓缩步骤中，浓缩的温度为60～80℃，真空度为-0.1～-0.05Mpa。
此外，待提纯水溶液的配置体积为待提纯母液体积的0.5～1倍，也就是说，待 提纯水溶液的体积是提前预设好的，不管在浓缩步骤中，待提纯母液被蒸发掉多少液体，均通过加水将待提纯母液的体积补充到待提纯水溶液的配置体积的值，这样能够达到比较理想的萃取和结晶效果。
氧化剂的种类和用量
在本申请的一些实施例中，对氧化剂进行了筛选，在筛选氧化剂的时候发现，选用双氧水、臭氧两种常规氧化剂进行氧化时，添加量如果控制不合理，容易导致目标产物三氯蔗糖-6-乙酯的氧化。此外，由于双氧水的加入，容易在体系中形成过氧化物，当过氧化物较多，且无法保证搅拌及降温的情况下，极易产生爆炸的危险。
通过多次探索，发明人发现，当氧化剂为次氯酸钠、氯酸钠和次氯酸钙中的一种时，选择氧化性是比较好的，尤其是次氯酸钠能够达到最理想的选择性氧化效果，即能够将三氯蔗糖双酯和四氯代蔗糖-6-酯氧化为三氯蔗糖-6-酯，同时也会将三氯蔗糖-6-酯进一步氧化。且发明人还发现，氧化剂的用量为待提纯母液中三氯蔗糖双酯和四氯代蔗糖-6-酯总质量的1～1.5倍时，能够达到更加理想的效果。
脱色剂的种类和用量
在本申请的一些实施例中，对脱色剂的种类和用量不作限制，在另一些实施例中，脱色剂为活性炭、凹凸棒土、硅藻土和活性白土中的一种或几种，在又一些实施例中，脱色剂为活性炭。上述脱色剂均为固体脱色剂，能够很好吸附蔗糖聚合形成的有色杂质。
在本申请的一些实施例中，对脱色剂的用量不作限制，在另一些实施例中，脱色剂的用量为待提纯水溶液的0.05～0.2wt％。由于有色杂质的含量是比较少的，从经济的角度，推荐脱色剂的用量为待提纯水溶液的0.05～0.2wt％即可。
在本申请的一些实施例中，对氧化脱色反应的温度和时间不作限制，可参考现有技术中氧化反应的范围，保障反应完全即可；在另一些实施例中，氧化脱色反应的温度为40～60℃，反应时间1～4h；若反应温度小于40℃，反应时间短于1h，反应条件比较温和，容易出现氧化反应进行不彻底的问题；若反应温度大于60℃，反应时间长于4h，有可能过度反应，甚至将三氯蔗糖-6-酯一并氧化。
碱解剂的种类和用量
在本申请的一些实施例中，对碱解剂的种类不作限制，采用碱性物质均可，在另一些实施例中，碱解剂为氨水或NaOH，在又一些实施例中，碱解剂为氨水。
在本申请的一些实施例中，对碱解剂的用量不作限制，达到碱性环境即可，在 另一些实施例中，碱解剂的用量以将待提纯水溶液的pH值调节至8.5-10.5为基准。
pH值调节条件
在本申请的一些实施例中，对第一滤液调解至中性的条件不作限制，采用酸性物质与第一滤液进行中和反应，调节至中性即可。
酸性物质为常见调节pH值的试剂即可，如稀盐酸或稀硫酸，在一些实施例中，可采用稀盐酸。
萃取剂的种类和用量
在本申请的一些实施例中，对萃取剂的种类和用量不作限制，凡是能够有效溶解一氯代蔗糖-6-酯、二氯代蔗糖-6-酯等酯类即可。在本申请的另一些实施例中，萃取剂为乙酸甲酯、乙酸乙酯、乙酸丙酯、乙酸异丙酯、乙酸丁酯和乙酸异丁酯中的一种或几种的混合物，在又一些实施例中为乙酸乙酯。由于目标产物三氯代蔗糖-6-酯，以及杂质一氯代蔗糖-6-酯、二氯代蔗糖-6-酯、三氯蔗糖双酯和四氯代蔗糖-6-酯均可溶解于上述酯类和水，但是在萃取剂中的溶解度大于在水中的溶解度，因此，可将目标产物中的部分有机酯类杂质从目标产物中萃取出，以提高目标产物三氯蔗糖-6-酯的纯度。这里需要说明的是，在萃取的过程中，也会有极小部分的目标产物三氯代蔗糖-6-酯被萃取剂带走。
本申请的一些实施例中，对萃取剂的用量不作限制，满足萃取要求即可，在另一些实施例中，出于经济因素的考虑，萃取剂的体积用量与待提纯水溶液的体积的比为1:1～3。
结晶的条件
在本申请中，萃取和结晶是同步进行的，三氯蔗糖-6-酯是制备三氯蔗糖的中间体，由于对终产物三氯蔗糖的纯度要求较高，因此需要三氯蔗糖-6-酯有较高的纯度，因此，在本申请中，一边萃取一边结晶，以除去三氯蔗糖-6-酯中，与其结构类似的有机酯杂质。
在本申请的一些实施例中，对结晶的条件不作限制，凡是能够将三氯蔗糖-6-酯有效结晶出即可，在本申请的另一些实施例中，将萃取和结晶综合考虑，筛选出在结晶步骤中，结晶的结晶温度为-10～10℃，结晶时间为6～12h。在这个条件范围内，既能够通过萃取有效去除杂质，又能够使得三氯蔗糖-6-酯达到比较理想的收率，不至于对三氯蔗糖-6-酯造成很多损失。
为了实现上述三氯蔗糖-6-酯的提纯方法，本申请设计了一套三氯蔗糖-6-酯的提纯设备，如图2所示，图2示出了根据本申请的一个实施例的三氯蔗糖-6-酯的 提纯装置的结构示意图，从图2可以看出，该提纯装置200包括：
脱溶釜V-1；氧化釜V-2；中和釜V-3；结晶釜V-4；分相器V-5；脱酯釜V-6；萃取釜V-7；酯结晶釜V-8；水结晶釜V-9，以及板框压滤机E-1、E-2、E-3、E-4。
其中，脱溶釜V-1的出口连接氧化釜V-2的入口；氧化釜V-2的出口连接中和釜V-3的入口，中和釜V-3的出口连接板框压滤机E-1的入口；板框压滤机E-1的液体出口连接结晶釜V-4的入口；结晶釜V-4的出口连接板框压滤机E-2的入口；板框压滤机E-2的固态物质出口连接酯结晶釜V-8；酯结晶釜V-8的出口连接板框压滤机E-3的入口；板框压滤机E-3的固态物质出口连接水结晶釜V-9；水结晶釜V-9的出口连接板框压滤机E-4；板框压滤机E-2的液态物质出口连接分相器V-5；分相器V-5的上端出口连接脱酯釜V-6；分相器V-5的下端出口连接萃取釜V-7。需要说明的是，上述描述仅是提纯装置200的主要连接关系，各个釜或者板框压滤机直接的连接关系可以根据需要进行适应性调整，且各个釜的类型可以根据各自的功能需要进行选择，本申请不作限制，如脱溶釜V-1可以选择蒸发型的反应釜，必要时可以设置真空泵；另外，也可以根据需要对上述提纯装置200中的各个釜或者板框压滤机进行增加或删减。
采用上述装置实施三滤蔗糖-6-酯的提纯方法，具体过程可简述如下：
将氯代反应中和液，即待提纯母液，输入脱溶釜V-1浓缩，以脱去绝大部分溶剂DMF和三氯乙烷，然后加入纯水(和/或水结晶母液)制成待提纯水溶液。
将待提纯水溶液输入氧化釜V-2，依次加入氧化剂和脱色剂，在一定条件下反应一段时间后，加入碱解剂直至待提纯水溶液的pH到达预设值，如8.5～10.5，继续保持反应一段时间。
反应结束后，进入板框压滤机E-1压滤分离，得到固体和第一滤液；分离出的固体作固废处理，第一滤液进入中和釜V-3，调节pH值后进入结晶釜V-4，向结晶釜V-4中加入有机酯萃取剂(和第二有机相)，有机酯萃取剂与第一滤液混合，同时进行萃取结晶，结晶完成后送入板框压滤机E-2压滤分离，得到固体结晶和第二滤液，分离出的固体为三氯蔗糖-6-乙酯粗品，第二滤液进入分相器V-5。
从分相器V-5下端分出第一水相进入萃取釜V-7；从分相器V-5上端分出有机酯相(第一有机相)，进入脱酯釜V-6，蒸发脱除有机酯后，剩余糖渣，加水溶解糖渣，溶解完成后，不溶于水的糖渣做废物处理，溶于水的糖渣形成糖渣水溶液，将糖渣水溶液输入萃取釜V-7中与第一水相混合。
向萃取釜V-7中加入有机酯萃取剂，萃取完成后，上相为有机酯相(第二有机 相)，将第二有机相送入结晶釜V-3参与结晶，下相为第二水相，第二水相作为高盐废水处理。
从板框压滤机E-2分离出的三氯蔗糖-6-乙酯粗品输入酯结晶釜V-8，加入有机酯萃取剂进行酯结晶，结晶完成后送入板框压滤机E-3；经压滤机压滤后获得酯结晶粗品(中间结晶体)，送入水结晶釜V-9，向水结晶釜V-9中加入纯水，结晶后送入板框压滤机E-4压滤分离，得到三氯蔗糖-6-乙酯精品和第四滤液，第四滤液为水结晶母液，可送入脱溶釜V-1用于配置待提纯水溶液。
待提纯母液来源
待提纯母液，也称氯代反应中和液，为生产三氯蔗糖过程中的氯化工段产生的氯化液，经氨水中和，然后经盐酸调节pH至6-8得来，其中目标组分三氯蔗糖-6-乙酯，待氧化组分三氯蔗糖双酯和四氯蔗糖-6-乙酯含量均由液相色谱仪检测获得，其他实施例或对比例相同，不再一一赘述。
实施例1
氯代反应中和液组分见表1。
表1氯代反应中和液组分表
组分 三氯蔗糖-6-乙酯 三氯蔗糖双酯 四氯蔗糖-6-乙酯
质量浓度/g/L 53.87 5.34 4.85
将7m 3氯代反应中和液输入浓缩釜V-1浓缩，浓缩温度为80℃，真空度-0.05Mpa，浓缩结束后，加入水结晶母液和纯水制成浓缩水溶液，体积为4.9m 3；将浓缩水溶液输入氧化釜V-2，依次加入氧化剂次氯酸钠78.46kg(以中和液体积为基准)和脱色剂活性炭3.5kg(以中和液体积为基准)，在40℃反应4h，反应结束后，将物料压入中和釜V-3中，加入氨水，将体系pH调节至8.5，然后加入稀硫酸，调节pH至8，调节完毕后，物料进板框压滤机E-1压滤分离；分离出的固体作固废处理，滤液进结晶釜V-4；向结晶釜中加入乙酸乙酯及酯相萃取液与滤液混合结晶，乙酸乙酯与酯相萃取液总体积是滤液体积的1.5倍，结晶温度为0℃，结晶时间为12h。结晶完成后将物料输入板框压滤机E-2压滤分离；分离出的固体为三氯蔗糖-6-乙酯粗品，获得的粗品收率及纯度见表2。
表2三氯蔗糖-6-乙酯精品纯度及收率
Figure PCTCN2021104939-appb-000002
实施例2
氯代反应中和液组分见表3。
表3氯代反应中和液组分表
组分 三氯蔗糖-6-乙酯 三氯蔗糖双酯 四氯蔗糖-6-乙酯
质量浓度/g/L 54.03 4.28 5.11
将5m 3氯代反应中和液输入浓缩釜V-1浓缩，浓缩温度为85℃，真空度-0.07Mpa，浓缩结束后，加入水结晶母液和纯水制成浓缩水溶液，体积为3.5m 3；将浓缩水溶液输入氧化釜V-2，依次加入氧化剂次氯酸钠56.04kg(以中和液体积为基准)和脱色剂活性炭2.5kg(以中和液体积为基准)，在45℃反应3.5h，反应结束后物料进板框压滤机E-1压滤分离；分离出的固体作固废处理，滤液进中和釜V-3，加入氨水，将体系pH调节至9.5，然后加入稀硫酸，调节pH至7.5，调节完毕后将物料输入结晶釜V-4；向结晶釜中加入乙酸乙酯及酯相萃取液与滤液混合结晶，乙酸乙酯与酯相萃取液总体积是滤液体积的1.5倍，结晶温度为0℃，结晶时间为10h。结晶完成后将物料输入板框压滤机E-2压滤分离；分离出的固体为三氯蔗糖-6-乙酯粗品，获得的粗品收率及纯度见表4。
表4三氯蔗糖-6-乙酯精品纯度及收率
Figure PCTCN2021104939-appb-000003
实施例3
氯代反应中和液组分见表5。
表5氯代反应中和液组分表
组分 三氯蔗糖-6-乙酯 三氯蔗糖双酯 四氯蔗糖-6-乙酯
质量浓度/g/L 55.90 4.27 5.23
将1m 3氯代反应中和液输入浓缩釜V-1浓缩，浓缩温度为60℃，真空度-0.1Mpa， 浓缩结束后，加入水结晶母液和纯水制成浓缩水溶液，体积为0.5m 3；将浓缩水溶液输入氧化釜V-2，依次加入氧化剂次氯酸钠19kg(以中和液体积为基准)和脱色剂活性炭2kg(以中和液体积为基准)，在60℃反应1h，反应结束后，将物料压入中和釜V-3中，加入氨水，将体系pH调节至10.5，然后加入盐酸，调节pH至6.5，调节完毕后，物料进板框压滤机E-1压滤分离；分离出的固体作固废处理，滤液进结晶釜V-4；向结晶釜中加入乙酸甲酯及酯相萃取液与滤液混合结晶，乙酸甲酯与酯相萃取液总体积是滤液体积的3倍，结晶温度为-10℃，结晶时间为6h。结晶完成后将物料输入板框压滤机E-2压滤分离；分离出的固体为三氯蔗糖-6-乙酯粗品，滤液进入分相器V-5；从分相器上端分出有机酯相，进入脱酯釜V-6，蒸发脱除有机酯后，加水溶解糖渣，水加入量为酯体积的0.5倍，溶解温度为70℃，时间0.5h。溶解完成后，将水溶液输入萃取釜V-7，对不溶糖渣作废物处理；从分相器下端分出水相进入萃取釜V-7，向其加入乙酸甲酯进行萃取，萃取比例为乙酸甲酯:水溶液＝0.1:1，萃取完成后，上相酯相萃取液送入结晶釜V-3参与结晶，下相水相作为高盐废水处理；从板框压滤机E-2分离出的三氯蔗糖-6-乙酯粗品1输入酯结晶釜V-8，加入乙酸甲酯进行酯结晶，加入量为粗品1:乙酸甲酯＝1:2，结晶温度为-5℃，结晶时间为0.5h。结晶完成后送入板框压滤机E-3；经压滤机压滤后获得酯结晶粗品2，送入水结晶釜V-9；向水结晶釜V-9中加入纯水，加入量为粗品2:纯水＝1:2，结晶温度为0℃，结晶时间为1h。结晶完成后送入板框压滤机E-4压滤分离，分离后得到三氯蔗糖-6-乙酯精品，水结晶母液送入浓缩釜V-1用于配置浓缩水溶液。获得的粗品收率及纯度见表6。
表6三氯蔗糖-6-乙酯精品纯度及收率
Figure PCTCN2021104939-appb-000004
注：收率以氯代反应中和液中的三氯蔗糖-6-乙酯的初始含量计算(其他实施例相同)。
实施例4
氯代反应中和液组分见表7。
表4氯代反应中和液组分表
组分 三氯蔗糖-6-乙酯 三氯蔗糖双酯 四氯蔗糖-6-乙酯
质量浓度/g/L 60.37 3.21 6.73
将2m 3氯代反应中和液输入浓缩釜V-1浓缩，浓缩温度为80℃，真空度-0.05Mpa，浓缩结束后，加入水结晶母液和纯水制成浓缩水溶液，体积为2m 3；将浓缩水溶液输入氧化釜V-2，依次加入氧化剂次氯酸钠27.83kg(以中和液体积为基准)和脱色剂活性炭3.8kg(以中和液体积为基准)，在55℃反应1.5h，反应结束后，将物料压入中和釜V-3中，加入20wt％氢氧化钠，将体系pH调节至10.5，然后加入盐酸，调节pH至6.5，调节完毕后，物料进板框压滤机E-1压滤分离；分离出的固体作固废处理，滤液进结晶釜V-4；向结晶釜中加入乙酸乙酯及酯相萃取液与滤液混合结晶，乙酸乙酯与酯相萃取液总体积是滤液体积的1倍，结晶温度为-5℃，结晶时间为7h。结晶完成后将物料输入板框压滤机E-2压滤分离；分离出的固体为三氯蔗糖-6-乙酯粗品，滤液进入分相器V-5；从分相器上端分出有机酯相，进入脱酯釜V-6，蒸发脱除有机酯后，加水溶解糖渣，水加入量为酯体积的2倍，溶解温度为40℃，时间2h。溶解完成后，将水溶液输入萃取釜V-7，对不溶糖渣作废物处理；从分相器下端分出水相进入萃取釜V-7，向其加入乙酸乙酯进行萃取，萃取比例为乙酸乙酯:水溶液＝0.5:1，萃取完成后，上相酯相萃取液送入结晶釜V-3参与结晶，下相水相作为高盐废水处理；从板框压滤机E-2分离出的三氯蔗糖-6-乙酯粗品1输入酯结晶釜V-8，加入乙酸乙酯进行酯结晶，加入量为粗品1:乙酸乙酯＝1:2.5，结晶温度为0℃，结晶时间为1.5h。结晶完成后送入板框压滤机E-3；经压滤机压滤后获得酯结晶粗品2，送入水结晶釜V-9；向水结晶釜V-9中加入纯水，加入量为粗品2:纯水＝1:3，结晶温度为5℃，结晶时间为2h。结晶完成后送入板框压滤机E-4压滤分离，分离后得到三氯蔗糖-6-乙酯精品，水结晶母液送入浓缩釜V-1用于配置浓缩水溶液。获得的粗品收率及纯度见表8。
表8三氯蔗糖-6-乙酯精品纯度及收率
Figure PCTCN2021104939-appb-000005
实施例5
氯代反应中和液组分见表9。
表9氯代反应中和液组分表
组分 三氯蔗糖-6-乙酯 三氯蔗糖双酯 四氯蔗糖-6-乙酯
质量浓度/g/L 50.39 6.82 4.71
将3m 3氯代反应中和液输入浓缩釜V-1浓缩，浓缩温度为70℃，真空度-0.07Mpa，浓缩结束后，加入水结晶母液和纯水制成浓缩水溶液，体积为2.1m 3；将浓缩水溶液输入氧化釜V-2，依次加入氧化剂次氯酸钠51.89kg(以中和液体积为基准)和脱色剂活性炭5.4kg(以中和液体积为基准)，在45℃反应3h，反应结束后，将物料压入中和釜V-3中，加入氨水，将体系pH调节至10，然后加入稀硫酸，调节pH至7.5，调节完毕后，物料进板框压滤机E-1压滤分离；分离出的固体作固废处理，滤液进结晶釜V-4；向结晶釜中加入乙酸异丁酯及酯相萃取液与滤液混合结晶，乙酸异丁酯与酯相萃取液总体积是滤液体积的1.5倍，结晶温度为0℃，结晶时间为8h。结晶完成后将物料输入板框压滤机E-2压滤分离；分离出的固体为三氯蔗糖-6-乙酯粗品，滤液进入分相器V-5；从分相器上端分出有机酯相，进入脱酯釜V-6，蒸发脱除有机酯后，加水溶解糖渣，水加入量为酯体积的1.5倍，溶解温度为50℃，时间1.5h。溶解完成后，将水溶液输入萃取釜V-7，对不溶糖渣作废物处理；从分相器下端分出水相进入萃取釜V-7，向其加入乙酸异丁酯进行萃取，萃取比例为乙酸异丁酯:水溶液＝0.7:1，萃取完成后，上相酯相萃取液送入结晶釜V-3参与结晶，下相水相作为高盐废水处理；从板框压滤机E-2分离出的三氯蔗糖-6-乙酯粗品1输入酯结晶釜V-8，加入乙酸异丁酯进行酯结晶，加入量为粗品1:乙酸异丁酯＝1:3.5，结晶温度为10℃，结晶时间为3h。结晶完成后送入板框压滤机E-3；经压滤机压滤后获得酯结晶粗品2，送入水结晶釜V-9；向水结晶釜V-9中加入纯水，加入量为粗品2:纯水＝1:4，结晶温度为15℃，结晶时间为3h。结晶完成后送入板框压滤机E-4压滤分离，分离后得到三氯蔗糖-6-乙酯精品，水结晶母液送入浓缩釜V-1用于配置浓缩水溶液。获得的粗品收率及纯度见表10。
表10三氯蔗糖-6-乙酯精品纯度及收率
Figure PCTCN2021104939-appb-000006
实施例6
氯代反应中和液组分见表11。
表11氯代反应中和液组分表
组分 三氯蔗糖-6-乙酯 三氯蔗糖双酯 四氯蔗糖-6-乙酯
质量浓度/g/L 51.88 5.88 5.97
将4m 3氯代反应中和液输入浓缩釜V-1浓缩，浓缩温度为65℃，真空度-0.08Mpa，浓缩结束后，加入水结晶母液和纯水制成浓缩水溶液，体积为3.2m 3；将浓缩水溶液输入氧化釜V-2，依次加入氧化剂次氯酸钠61.62kg(以中和液体积为基准)和脱色剂活性炭6.4kg(以中和液体积为基准)，在60℃反应1h，反应结束后，将物料压入中和釜V-3中，加入20wt％氢氧化钠，将体系pH调节至8.5，然后加入稀硫酸，调节pH至6.5，调节完毕后，物料进板框压滤机E-1压滤分离；分离出的固体作固废处理，滤液进结晶釜V-4；向结晶釜中加入乙酸丁酯及酯相萃取液与滤液混合结晶，乙酸丁酯与酯相萃取液总体积是滤液体积的2倍，结晶温度为5℃，结晶时间为10h。结晶完成后将物料输入板框压滤机E-2压滤分离；分离出的固体为三氯蔗糖-6-乙酯粗品，滤液进入分相器V-5；从分相器上端分出有机酯相，进入脱酯釜V-6，蒸发脱除有机酯后，加水溶解糖渣，水加入量为酯体积的0.5倍，溶解温度为70℃，时间0.5h。溶解完成后，将水溶液输入萃取釜V-7，对不溶糖渣作废物处理；从分相器下端分出水相进入萃取釜V-7，向其加入乙酸丁酯进行萃取，萃取比例为乙酸丁酯:水溶液＝0.3:1，萃取完成后，上相酯相萃取液送入结晶釜V-3参与结晶，下相水相作为高盐废水处理；从板框压滤机E-2分离出的三氯蔗糖-6-乙酯粗品1输入酯结晶釜V-8，加入乙酸丁酯进行酯结晶，加入量为粗品1:乙酸丁酯＝1:4.5，结晶温度为5℃，结晶时间为2h。结晶完成后送入板框压滤机E-3；经压滤机压滤后获得酯结晶粗品2，送入水结晶釜V-9；向水结晶釜V-9中加入纯水，加入量为粗品2:纯水＝1:5，结晶温度为30℃，结晶时间为5h。结晶完成后送入板框压滤机E-4压滤分离，分离后得到三氯蔗糖-6-乙酯精品，水结晶母液送入浓缩釜V-1用于配置浓缩水溶液。获得的粗品收率及纯度见表12。
表12三氯蔗糖-6-乙酯精品纯度及收率
Figure PCTCN2021104939-appb-000007
实施例7
氯代反应中和液组分见表13。
表13氯代反应中和液组分表
组分 三氯蔗糖-6-乙酯 三氯蔗糖双酯 四氯蔗糖-6-乙酯
质量浓度/g/L 54.31 4.29 6.76
将5m 3氯代反应中和液输入浓缩釜V-1浓缩，浓缩温度为75℃，真空度-0.06Mpa，浓缩结束后，加入水结晶母液和纯水制成浓缩水溶液，体积为4.5m 3；将浓缩水溶液输入氧化釜V-2，依次加入氧化剂次氯酸钠71.83kg(以中和液体积为基准)和脱色剂活性炭7.5kg(以中和液体积为基准)，在50℃反应2h，反应结束后，将物料压入中和釜V-3中，加入氨水，将体系pH调节至8.5，然后加入稀硫酸，调节pH至7.5，调节完毕后，物料进板框压滤机E-1压滤分离；分离出的固体作固废处理，滤液进结晶釜V-4；向结晶釜中加入乙酸异丙酯及酯相萃取液与滤液混合结晶，乙酸异丙酯与酯相萃取液总体积是滤液体积的2.5倍，结晶温度为10℃，结晶时间为12h。结晶完成后将物料输入板框压滤机E-2压滤分离；分离出的固体为三氯蔗糖-6-乙酯粗品，滤液进入分相器V-5；从分相器上端分出有机酯相，进入脱酯釜V-6，蒸发脱除有机酯后，加水溶解糖渣，水加入量为酯体积的1倍，溶解温度为60℃，时间1h。溶解完成后，将水溶液输入萃取釜V-7，对不溶糖渣作废物处理；从分相器下端分出水相进入萃取釜V-7，向其加入乙酸异丙酯进行萃取，萃取比例为乙酸异丙酯:水溶液＝1:1，萃取完成后，上相酯相萃取液送入结晶釜V-3参与结晶，下相水相作为高盐废水处理；从板框压滤机E-2分离出的三氯蔗糖-6-乙酯粗品1输入酯结晶釜V-8，加入乙酸异丙酯进行酯结晶，加入量为粗品1:乙酸异丙酯＝1:5，结晶温度为10℃，结晶时间为3h。结晶完成后送入板框压滤机E-3；经压滤机压滤后获得酯结晶粗品2，送入水结晶釜V-9；向水结晶釜V-9中加入纯水，加入量为粗品2:纯水＝1:3，结晶温度为25℃，结晶时间为4h。结晶完成后送入板框压滤机E-4压滤分离，分离后得到三氯蔗糖-6-乙酯精品，水结晶母液送入浓缩釜V-1用于配置浓缩水溶液。获得的粗品收率及纯度见表14。
表14三氯蔗糖-6-乙酯精品纯度及收率
Figure PCTCN2021104939-appb-000008
实施例8
氯代反应中和液组分见表15。
表15氯代反应中和液组分表
组分 三氯蔗糖-6-乙酯 三氯蔗糖双酯 四氯蔗糖-6-乙酯
质量浓度/g/L 52.99 3.99 6.12
将6m 3氯代反应中和液输入浓缩釜V-1浓缩，浓缩温度为60℃，真空度-0.1Mpa，浓缩结束后，加入水结晶母液和纯水制成浓缩水溶液，体积为3.6m 3；将浓缩水溶液输入氧化釜V-2，依次加入氧化剂次氯酸钠72.79kg(以中和液体积为基准)和脱色剂活性炭6kg(以中和液体积为基准)，在50℃反应3h，反应结束后，将物料压入中和釜V-3中，加入20wt％氢氧化钠，将体系pH调节至9.5，然后加入盐酸，调节pH至8，调节完毕后，物料进板框压滤机E-1压滤分离；分离出的固体作固废处理，滤液进结晶釜V-4；向结晶釜中加入乙酸丙酯及酯相萃取液与滤液混合结晶，乙酸甲酯与酯相萃取液总体积是滤液体积的1倍，结晶温度为-8℃，结晶时间为7h。结晶完成后将物料输入板框压滤机E-2压滤分离；分离出的固体为三氯蔗糖-6-乙酯粗品，滤液进入分相器V-5；从分相器上端分出有机酯相，进入脱酯釜V-6，蒸发脱除有机酯后，加水溶解糖渣，水加入量为酯体积的1.5倍，溶解温度为50℃，时间1.5h。溶解完成后，将水溶液输入萃取釜V-7，对不溶糖渣作废物处理；从分相器下端分出水相进入萃取釜V-7，向其加入乙酸丙酯进行萃取，萃取比例为乙酸丙酯:水溶液＝0.9:1，萃取完成后，上相酯相萃取液送入结晶釜V-3参与结晶，下相水相作为高盐废水处理；从板框压滤机E-2分离出的三氯蔗糖-6-乙酯粗品1输入酯结晶釜V-8，加入乙酸丙酯进行酯结晶，加入量为粗品1:乙酸丙酯＝1:4，结晶温度为5℃，结晶时间为2h。结晶完成后送入板框压滤机E-3；经压滤机压滤后获得酯结晶粗品2，送入水结晶釜V-9；向水结晶釜V-9中加入纯水，加入量为粗品2:纯水＝1:5，结晶温度为30℃，结晶时间为5h。结晶完成后送入板框压滤机E-4压滤分离，分离后得到三氯蔗糖-6-乙酯精品，水结晶母液送入浓缩釜V-1用于配置浓缩水溶液。获得的粗品收率及纯度见表16。
表16三氯蔗糖-6-乙酯精品纯度及收率
Figure PCTCN2021104939-appb-000009
实施例9
氯代反应中和液组分见表17。
表17氯代反应中和液组分表
组分 三氯蔗糖-6-乙酯 三氯蔗糖双酯 四氯蔗糖-6-乙酯
质量浓度/g/L 53.87 5.34 4.85
将7m 3氯代反应中和液输入浓缩釜V-1浓缩，浓缩温度为80℃，真空度-0.05Mpa，浓缩结束后，加入水结晶母液和纯水制成浓缩水溶液，体积为4.9m 3；将浓缩水溶液输入氧化釜V-2，依次加入氧化剂次氯酸钠78.46kg(以中和液体积为基准)和脱色剂活性炭3.5kg(以中和液体积为基准)，在40℃反应4h，反应结束后，将物料压入中和釜V-3中，加入氨水，将体系pH调节至8.5，然后加入稀硫酸，调节pH至8，调节完毕后，物料进板框压滤机E-1压滤分离；分离出的固体作固废处理，滤液进结晶釜V-4；向结晶釜中加入乙酸乙酯及酯相萃取液与滤液混合结晶，乙酸乙酯与酯相萃取液总体积是滤液体积的1.5倍，结晶温度为0℃，结晶时间为12h。结晶完成后将物料输入板框压滤机E-2压滤分离；分离出的固体为三氯蔗糖-6-乙酯粗品，滤液进入分相器V-5；从分相器上端分出有机酯相，进入脱酯釜V-6，蒸发脱除有机酯后，加水溶解糖渣，水加入量为酯体积的2倍，溶解温度为40℃，时间2h。溶解完成后，将水溶液输入萃取釜V-7，对不溶糖渣作废物处理；从分相器下端分出水相进入萃取釜V-7，向其加入乙酸乙酯进行萃取，萃取比例为乙酸乙酯:水溶液＝0.2:1，萃取完成后，上相酯相萃取液送入结晶釜V-3参与结晶，下相水相作为高盐废水处理；从板框压滤机E-2分离出的三氯蔗糖-6-乙酯粗品1输入酯结晶釜V-8，加入乙酸乙酯进行酯结晶，加入量为粗品1:乙酸乙酯＝1:3，结晶温度为0℃，结晶时间为1h。结晶完成后送入板框压滤机E-3；经压滤机压滤后获得酯结晶粗品2，送入水结晶釜V-9；向水结晶釜V-9中加入纯水，加入量为粗品2:纯水＝1:3.5，结晶温度为5℃，结晶时间为5h。结晶完成后送入板框压滤机E-4压滤分离，分离后得到三氯蔗糖-6-乙酯精品，水结晶母液送入浓缩釜V-1用于配置浓缩水溶液。获得的粗品收率及纯度见表18。
表18三氯蔗糖-6-乙酯精品纯度及收率
Figure PCTCN2021104939-appb-000010
实施例10
氯代反应中和液组分见表19。
表19氯代反应中和液组分表
组分 三氯蔗糖-6-乙酯 三氯蔗糖双酯 四氯蔗糖-6-乙酯
质量浓度/g/L 58.59 5.38 6.97
将3m 3氯代反应中和液输入浓缩釜V-1浓缩，浓缩温度为60℃，真空度-0.1Mpa，浓缩结束后，加入水结晶母液和纯水制成浓缩水溶液，体积为原氯代反应中和液体积的1倍；将浓缩水溶液输入氧化釜V-2。依次加入氧化剂次氯酸钠55.57kg(以中和液体积为基准)和脱色剂活性炭4kg(以中和液体积为基准)；在60℃反应2h，反应结束后，将物料压入中和釜V-3中，加入氨水，将体系pH调节至9.5，然后加入稀盐酸，调节pH至7.5，调节完毕后，物料进板框压滤机E-1压滤分离；分离出的固体作固废处理，滤液进结晶釜V-4；向结晶釜中加入乙酸乙酯及酯相萃取液与滤液混合结晶，乙酸乙酯与酯相萃取液总体积是滤液体积的2.5倍，结晶温度为-5℃，结晶时间为8h。结晶完成后将物料输入板框压滤机E-2压滤分离；分离出的固体为三氯蔗糖-6-乙酯粗品，滤液进入分相器V-5；从分相器上端分出有机酯相，进入脱酯釜V-6，蒸发脱除有机酯后，加水溶解糖渣，水加入量为酯体积的1倍，溶解温度为60℃，时间2h。溶解完成后，将水溶液输入萃取釜V-7，对不溶糖渣作废物处理；从分相器下端分出水相进入萃取釜V-7，向其加入乙酸乙酯进行萃取，萃取比例为乙酸乙酯:水溶液＝0.2:1，萃取完成后，上相酯相萃取液送入结晶釜V-3参与结晶，下相水相作为高盐废水处理；从板框压滤机E-2分离出的三氯蔗糖-6-乙酯粗品1输入酯结晶釜V-8，加入乙酸乙酯进行酯结晶，加入量为粗品1:乙酸甲酯＝1:2.5，结晶温度为0℃，结晶时间为2h。结晶完成后送入板框压滤机E-3；经压滤机压滤后获得酯结晶粗品2，送入水结晶釜V-9；向水结晶釜V-9中加入纯水，加入量为粗品2:纯水＝1:3，结晶温度为5℃，结晶时间为2h。结晶完成后送入板框压滤机E-4压滤分离，分离后得到三氯蔗糖-6-乙酯精品，水结晶母液送入浓缩釜V-1用于配置浓缩水溶液。获得的粗品收率及纯度见表20。
表20三氯蔗糖-6-乙酯精品纯度及收率对比
Figure PCTCN2021104939-appb-000011
对比例1
为了进一步证明加入氧化剂后三氯蔗糖-6-乙酯的收率高于常规提纯操作，本对比例选用与实施例10同种样品，同等操作进行三氯蔗糖-6-乙酯的提纯，不同之 处在于，实施例10中加入氧化剂，对比例1不加氧化剂。氯代反应中和液组分见表21。
表21氯代反应中和液组分表
组分 三氯蔗糖-6-乙酯 三氯蔗糖双酯 四氯蔗糖-6-乙酯
质量浓度/g/L 58.59 5.38 6.97
将3m 3氯代反应中和液输入浓缩釜V-1浓缩，浓缩温度为60℃，真空度-0.1Mpa，浓缩结束后，加入水结晶母液和纯水制成浓缩水溶液，体积为原氯代反应中和液体积的1倍；将浓缩水溶液输入氧化釜V-2。方法一：依次加入氧化剂次氯酸钠55.57kg(以中和液体积为基准)和脱色剂活性炭4kg(以中和液体积为基准)；方法二：加入脱色剂活性炭4kg(以中和液体积为基准)，在60℃反应2h，反应结束后，将物料压入中和釜V-3中，加入氨水，将体系pH调节至9.5，然后加入盐酸，调节pH至7.5，调节完毕后，物料进板框压滤机E-1压滤分离；分离出的固体作固废处理，滤液进结晶釜V-4；向结晶釜中加入乙酸乙酯及酯相萃取液与滤液混合结晶，乙酸乙酯与酯相萃取液总体积是滤液体积的2.5倍，结晶温度为-5℃，结晶时间为8h。结晶完成后将物料输入板框压滤机E-2压滤分离；分离出的固体为三氯蔗糖-6-乙酯粗品，滤液进入分相器V-5；从分相器上端分出有机酯相，进入脱酯釜V-6，蒸发脱除有机酯后，加水溶解糖渣，水加入量为酯体积的1倍，溶解温度为60℃，时间2h。溶解完成后，将水溶液输入萃取釜V-7，对不溶糖渣作废物处理；从分相器下端分出水相进入萃取釜V-7，向其加入乙酸乙酯进行萃取，萃取比例为乙酸乙酯:水溶液＝0.2:1，萃取完成后，上相酯相萃取液送入结晶釜V-3参与结晶，下相水相作为高盐废水处理；从板框压滤机E-2分离出的三氯蔗糖-6-乙酯粗品1输入酯结晶釜V-8，加入乙酸乙酯进行酯结晶，加入量为粗品1:乙酸甲酯＝1:2.5，结晶温度为0℃，结晶时间为2h。结晶完成后送入板框压滤机E-3；经压滤机压滤后获得酯结晶粗品2，送入水结晶釜V-9；向水结晶釜V-9中加入纯水，加入量为粗品2:纯水＝1:3，结晶温度为5℃，结晶时间为2h。结晶完成后送入板框压滤机E-4压滤分离，分离后得到三氯蔗糖-6-乙酯精品，水结晶母液送入浓缩釜V-1用于配置浓缩水溶液。获得的粗品收率及纯度见表22。
表22三氯蔗糖-6-乙酯精品纯度及收率对比
Figure PCTCN2021104939-appb-000012
由表20和表22可以看出，加入氧化剂将副产物三氯蔗糖双酯和四氯蔗糖-6-乙酯氧化成目标产物三氯蔗糖-6-乙酯后，可以显著提高三氯蔗糖-6-乙酯的收率。
综上所述，本申请的一种三氯蔗糖-6-乙酯的提纯方法，通过在提纯过程中加入氧化剂，将三氯蔗糖双酯和四氯蔗糖-6-乙酯两种杂质氧化，转换成目标产物三氯蔗糖-6-乙酯，从而提高整体三氯蔗糖-6-乙酯收率，一方面提高了三氯蔗糖-6-乙酯的产能，另一方面降低了高盐废水的COD含量，缓解了后续生化处理的压力。此外，该法简化操作，缩短流程，实现了降本增效，能够创造较大的经济效益。
在本申请的描述中，需要说明的是，术语“中心”、“上”、“下”、“左”、“右”、“竖直”、“水平”、“内”、“外”等指示的方位或位置关系为基于附图所示的方位或位置关系，仅是为了便于描述本申请和简化描述，而不是指示或暗示所指的装置或元件必须具有特定的方位、以特定的方位构造和操作，因此不能理解为对本申请的限制。此外，术语“第一”、“第二”、“第三”等仅用于描述目的，而不能理解为指示或暗示相对重要性。
在本申请的描述中，需要说明的是，除非另有明确的规定和限定，术语“安装”、“相连”、“连接”应做广义理解，例如，可以是固定连接，也可以是可拆卸连接，或一体地连接；可以是机械连接，也可以是电连接；可以是直接相连，也可以通过中间媒介间接相连，可以是两个元件内部的连通。对于本领域的普通技术人员而言，可以具体情况理解上述术语在本申请中的具体含义。
以上所述，仅为本申请的具体实施方式，在本申请的上述教导下，本领域技术人员可以在上述实施例的基础上进行其他的改进或变形。本领域技术人员应该明白，上述的具体描述只是更好的解释本申请的目的，本申请的保护范围应以权利要求的保护范围为准。
此外，本领域的技术人员能够理解，尽管在此所述的一些实施例包括其它实施例中所包括的某些特征而不是其它特征，但是不同实施例的特征的组合意味着处于本申请的范围之内并且形成不同的实施例。例如，在下面的权利要求书中，所要求保护的实施例的任意之一都可以以任意的组合方式来使用。

Claims (12)

  1. 一种三氯蔗糖-6-酯的提纯方法，其特征在于，包括：
    浓缩步骤：将待提纯母液进行浓缩，以脱除有机溶剂，浓缩完成后，向其中加入水，形成待提纯水溶液；其中，所述待提纯母液通过中和三氯蔗糖经酯化、氯代反应制备三氯蔗糖-6-酯的反应液得来；
    氧化步骤：向所述待提纯水溶液中依次加入氧化剂和脱色剂，进行氧化脱色反应，然后向所述待提纯水溶液中加入碱解剂，以将目标杂质氧化为三氯蔗糖-6-酯，以及脱除有色杂质；反应一段时间后，进行固液分离，得到固体废弃物和第一滤液；和
    结晶步骤：将所述第一滤液调解至中性后，加入萃取剂，同时进行萃取和结晶，得到三氯蔗糖-6-酯粗产品和第二滤液。
  2. 根据权利要求1所述的方法，其特征在于，所述方法还包括：
    滤液回收步骤：将所述第二滤液分层，得到第一有机相和第一水相，将所述第一有机相进行蒸发，以脱除萃取剂，得到糖渣，加水溶解、固液分离后，得到糖渣水溶液；
    将所述糖渣水溶液与第一水相混合，并加入萃取剂进行萃取，将萃取得到的第二有机相回收至要进入所述结晶步骤的第一滤液中。
  3. 根据权利要求2所述的方法，其特征在于，在所述滤液回收步骤中，所述水的添加质量与所述第一有机相的质量的比为0.5～2:1，所述溶解的溶解温度为40～70℃，溶解时间为0.5～2h；
    所述萃取剂的体积用量与所述糖渣水溶液与所述第一水相的总体积的比为0.1～1:1。
  4. 根据权利要求2所述的方法，其特征在于，所述方法还包括：
    精制步骤：将得到的三氯蔗糖-6-酯粗产品溶解于萃取剂中，进行第一次结晶和分离，得到中间结晶体和第三滤液；
    将得到的中间结晶体溶解于水中，进行第二次结晶和分离，得到三氯蔗糖-6-酯精制产品和第四滤液。
  5. 根据权利要求4所述的方法，其特征在于，所述方法还包括：
    将第三滤液回收至要进入所述滤液回收步骤的第二滤液中；
    将第四滤液回收至要进入所述浓缩步骤的待提纯母液中。
  6. 根据权利要求4所述的方法，其特征在于，在所述精制步骤中，所述萃取剂的质量用量与所述三氯蔗糖-6-酯粗产品的质量的比为2～5:1；所述第一次结晶的结晶温度为-5～10℃，结晶时间为0.5～3h；
    所述水的质量用量与所述中间结晶体的质量的比为2～5:1；所述第二次结晶的结晶温度为0～30℃，结晶时间1～5h。
  7. 根据权利要求1所述的方法，其特征在于，在所述浓缩步骤中，所述浓缩的温度为60～80℃，真空度为-0.1～-0.05Mpa；
    所述待提纯水溶液的配置体积为所述待提纯母液体积的0.5～1倍。
  8. 根据权利要求1所述的方法，其特征在于，在所述氧化步骤中，所述氧化剂为次氯酸钠、氯酸钠和次氯酸钙中的一种，优选为次氯酸钠；
    所述氧化剂的用量为所述待提纯母液中目标杂质总质量的1～1.5倍。
  9. 根据权利要求1所述的方法，其特征在于，在所述氧化步骤中，所述脱色剂为活性炭、凹凸棒土、硅藻土和活性白土中的一种或几种，优选活性炭；
    所述脱色剂的用量为所述待提纯水溶液的0.05～0.2wt％；
    所述氧化脱色反应的温度为40～60℃，反应时间1～4h。
  10. 根据权利要求1所述的方法，其特征在于，在所述氧化步骤中，所述碱解剂为氨水或NaOH，优选氨水；
    所述碱解剂的用量以将所述待提纯水溶液的pH值调节至8.5-10.5为基准。
  11. 根据权利要求1所述的方法，其特征在于，在所述结晶步骤中，所述将所述第一滤液调解至中性包括：
    采用酸性物质将所述第一滤液的pH值调节至6.5-8.0；其中，所述酸性物质为稀盐酸或稀硫酸，优选稀盐酸。
  12. 根据权利要求1所述的方法，其特征在于，在所述结晶步骤中，所述萃取剂为乙酸甲酯、乙酸乙酯、乙酸丙酯、乙酸异丙酯、乙酸丁酯和乙酸异丁酯中的一种或几种，优选为乙酸乙酯；
    所述萃取剂的体积用量与所述待提纯水溶液的体积的比为1:1～3；
    所述结晶的温度为-10～10℃，结晶时间为6～12h。
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