WO2023010323A1 - Method for preparing sucralose - Google Patents

Abstract

Provided is a method for preparing sucralose. The method comprises the steps of: feeding a chlorination reaction solution for preparing sucralose-6 ester, a first liquid alkali and first reuse water into a neutralization reaction rectifying column in sections, subjecting same to a neutralization reaction under evaporation conditions, and then extracting a solvent mixture from the top of the neutralization reaction rectifying column; extracting a chlorination reaction neutralization solution from the bottom of the neutralization reaction rectifying column; feeding the chlorination reaction neutralization solution, a second liquid alkali and second reuse water into a hydrolysis reaction rectifying column in sections, subjecting same to an alkaline hydrolysis reaction under evaporation conditions, extracting a waste aqueous solution from the top of the hydrolysis reaction rectifying column, and extracting a sucralose aqueous solution from the bottom of the hydrolysis reaction rectifying column; adjusting the sucralose aqueous solution to be neutral, then successively subjecting same to extraction, oxidation and back extraction for purification; and crystallization.

Description

The preparation method of sucralose technical field

The invention belongs to the technical field of fine chemicals, and in particular relates to a preparation method of sucralose.

Background of the invention

Sucralose, commonly known as sucralose, is white crystalline powder or granules in appearance, and its sweetness is about 600 times that of sucrose. As a new generation of sweetener, sucralose is the only one that uses sucrose as raw material. Calorie, does not participate in human metabolism, can be used by diabetics, patients with cardiovascular and cerebrovascular diseases and the elderly as "zero-calorie" sugar. The products have the characteristics of high stability, acid and alkali resistance, high temperature resistance, long shelf life and high safety, and are widely used in food, beverage, daily chemical, pharmaceutical and other fields.

Sucralose-6-ester is one of the important intermediates for the preparation of sucralose, which is obtained by chlorination of sucralose-6-ester and chlorination reagent at high temperature, because a large number of by-products and impurities will be produced during the chlorination process , these by-products and impurities affect the purity of the final product sucralose. In the prior art, to obtain pure sucralose usually requires neutralization, concentrated drying, extraction crystallization, ester knot, water knot, alcoholysis , Purification, concentration, crystallization and other operations to purify the chlorinated neutralization solution for the production of sucralose-6-ester, the process has poor continuity, cumbersome manual operation, large amount of ammonia water, and difficult biochemical treatment in the later stage.

At present, there are also reports about the continuous or one-pot method of preparing sucralose from chlorinated liquid containing sucralose-6-acetate, such as Chinese patent CN103113426, which reports a one-pot method using sucrose and boric anhydride as raw materials. The process of preparing sucralose by method, in which hexachlorosucrose borate is prepared, hexachlorosucrose borate is hydrolyzed by saturated inorganic salt solution to obtain sucralose, then extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered Finally, an ethyl acetate solution containing sucralose was obtained, and then decolorized by 95 wt% ethanol and activated carbon, and then filtered. Finally, the filtrate was crystallized to obtain pure sucralose. Although this method has strong continuity and high yield, it uses boric anhydride as a raw material, which is costly, difficult to recycle, difficult to follow-up wastewater treatment, and has little prospect for industrialization. In summary, there is an urgent need for a preparation method of sucralose to solve the above problems. It should be noted that the statements herein only provide background information related to the present application and do not necessarily constitute prior art.

Contents of the invention

In view of the existing technology, a preparation method of sucralose is provided, which abandons the traditional intermittent neutralization, precipitation, hydrolysis, and lengthy sucralose-6-acetate purification process, and realizes the sucralose Continuous preparation of sucrose to overcome the deficiencies in the prior art.

According to the first aspect of the present application, a method for preparing sucralose is provided, comprising:

Neutralization step: make the chlorination reaction solution for preparing sucralose-6 ester, the first liquid caustic soda and the first reused water enter the neutralization reaction distillation tower in sections, and after the neutralization reaction is carried out under the evaporation condition, from the neutralization reaction Extract the solvent mixture from the top of the rectifying tower; extract the chlorination reaction neutralizing liquid from the bottom of the column of the neutralization reaction rectification;

Hydrolysis step: make the chlorination reaction neutralization liquid, the second liquid alkali and the second recycled water enter the hydrolysis reaction rectification tower, carry out the alkaline hydrolysis reaction under the evaporation condition, and extract from the top of the hydrolysis reaction rectification tower The aqueous solution is discarded, and the sucralose aqueous solution is extracted from the bottom of the hydrolysis reaction distillation tower;

Extraction and purification step: after adjusting the sucralose aqueous solution to neutrality, sequentially perform extraction, oxidation and back extraction for purification; and

Crystallization step: Concentrate, crystallize and filter the purified sucralose aqueous solution to obtain crude sucralose product and crystallization mother liquor.

Optionally, the above method also includes:

Mother liquor circulation recovery step: the crystallization mother liquor is recycled into the sucralose aqueous solution to enter the crystallization step, and the number of recycling is 1 to 5 times.

Optionally, in the above method, the height of the neutralization reactive distillation tower is 10-30m;

The feeding position of the chlorination reaction liquid is at a position of 3/10 to 2/5 of the height of the tower from the top of the tower, and the feeding position of the first liquid alkali is at a position of 1/2 to 3/5 of the height of the tower from the top of the tower , the feeding position of the first recycled water is at a position of 7/10 to 4/5 of the tower height from the top of the tower.

Optionally, in the above method, in the neutralization step, during the neutralization reaction, the top temperature of the neutralization reaction distillation tower is set to 30-40°C, and the bottom temperature is set to 50-60°C.

Optionally, in the above method, in the hydrolysis step, the tower height of the hydrolysis reaction distillation tower is 10-30m;

The feed position of the chlorinated liquid neutralizing liquid is 2/5 to 3/7 of the height of the tower from the top of the tower, and the feed position of the second liquid alkali is 1/2 to 3/5 of the height of the tower from the top of the tower The position of the feed of the second return water is at a position of 4/5 to 9/10 of the height of the tower from the top of the tower.

Optionally, in the above method, in the hydrolysis step, during the hydrolysis reaction, the temperature at the top of the neutralization reaction distillation column is set at 30-40°C, and the temperature at the bottom of the column is set at 50-60°C.

Optionally, in the above method, both the neutralization reaction rectification tower and the hydrolysis reaction rectification tower are packed towers or plate towers, preferably packed towers, wherein the filler in the packed tower is polytetrafluoro corrugated plate or θ ring , The height of the packing is 1/3~2/3 of the height of the packed tower.

Optionally, in the above method, in the neutralization step, the volume ratio of the chlorination reaction solution, the first liquid caustic soda and the first recycled water is 10-15:1:1;

In the hydrolysis step, the volume ratio of the chlorination reaction neutralizing solution, the second liquid caustic soda and the second recycled water is 40-60:1:10-20.

Optionally, in the above method, both the first liquid alkali and the second liquid alkali are aqueous solutions of sodium hydroxide or potassium hydroxide, preferably aqueous solutions of sodium hydroxide.

Optionally, in the above method, in the extraction and purification step, adjusting the sucralose aqueous solution to neutrality includes:

The pH value of the sucralose aqueous solution is adjusted to 6-8 by adopting inorganic acid, wherein the inorganic acid is one of hydrochloric acid, sulfuric acid or phosphoric acid.

Optionally, in the above method, in the extraction and purification step, the extractant used for extraction is ethyl acetate and/or butyl acetate;

The ratio of the volumetric dosage of the extractant to the neutralizing solution for the chlorination reaction is 1-5:1.

Optionally, in the above method, in the extraction and purification step, the oxidant used for oxidation is sodium hypochlorite or ozone; wherein, the mass dosage of sodium hypochlorite is 0.01% to 0.1% of the volume of the organic phase obtained by extraction; the volume dosage of ozone is 0.01 to 0.1% of the volume of the obtained organic phase;

The oxidation time for oxidation is 3-12 hours.

Optionally, in the above method, in the extraction and purification step, the back-extraction agent for back-extraction is water, and the volume ratio of the back-extraction agent to the volume of the extracted organic phase is 1-5:1.

Optionally, in the above method, in the crystallization step, the concentration temperature is 40-60°C, the concentration vacuum is -0.1--0.5Mpa, and the sucralose concentration in the sucralose aqueous solution is 80-140g /L.

The beneficial effect of the present application is that the present application uses the untreated chlorinated reaction liquid obtained during the preparation of sucralose-6-ester as a raw material, and uses a neutralization reaction rectification tower to realize the neutralization and precipitation of the chlorinated liquid, and then uses the hydrolysis The rectification tower achieves the purpose of desolvation and hydrolysis of sucralose-6-ester to prepare sucralose, and finally through extraction-oxidation-back extraction, the continuous preparation of sucralose is realized. This application abandons the traditional batch process And, precipitation, hydrolysis, and lengthy sucralose-6-acetate purification process, significantly improved the efficiency of the preparation and purification of sucralose; and compared with the prior art, the application uses liquid caustic soda to The reaction solution is neutralized, and the use of ammonia water and sodium methoxide is discarded. On the one hand, it reduces the pressure brought by the ammonia nitrogen content in the later biochemical treatment; on the other hand, it avoids the use and production of methanol, which is highly environmentally friendly and is An efficient, green and continuous sucralose preparation process has extremely high application value and practicability.

The above description is only an overview of the technical solution of the present application. In order to better understand the technical means of the present application, it can be implemented according to the contents of the description, and in order to make the above and other purposes, features and advantages of the present application more obvious and understandable , the following specifically cites the specific implementation manner of the present application.

Brief description of the drawings

Various other advantages and benefits will become apparent to those of ordinary skill in the art upon reading the following detailed description of the preferred embodiment. The drawings are only for the purpose of illustrating the preferred embodiments and are not to be considered as limiting the application. Also throughout the drawings, the same reference numerals are used to designate the same components. In the attached picture:

Figure 1 shows a schematic structural view of a device for preparing sucralose according to an embodiment of the present application;

Fig. 2 shows a schematic flow diagram of a method for preparing sucralose-6-ester according to an embodiment of the present application.

Modes of Carrying Out the Invention

The applicant found through research on the production process of sucralose prepared from the chlorination reaction solution by the traditional method: the sucralose-6-ester in the chlorination reaction solution must be released after being neutralized by alkali. Sucralose-6-ester cannot be obtained from the chlorination reaction solution, and sucralose can be prepared from it; after neutralization, solvents such as DMF and trichloroethane must be evaporated to prevent alkaline hydrolysis in the later stage. The process of sucralose leads to the decomposition of DMF; there must be a purification operation in the process of preparing sucralose from sucralose-6-ester, otherwise the pure product of sucralose cannot be successfully obtained through crystallization, and the mother liquor cannot be recycled.

Therefore, in the process of preparing sucralose by adopting the traditional process, the ammonia water used in the neutralization process will lead to high pressure of ammonia nitrogen in the later biochemical treatment, and the use of sodium methoxide and methanol will affect the crystallization quality of the later product; the purification process requires a lot of complicated purification The technology has the defects of complex operation, low degree of continuity, high economic and time costs, and low yield of sucralose.

In view of the above problems, the present application proposes a continuous preparation method of sucralose. The technical concept is: through a two-stage reactive distillation tower, effectively combine neutralization and precipitating, effectively combine precipitating and hydrolysis, and improve the process continuity, reducing operation difficulty and production cost; using liquid caustic soda as neutralization and hydrolysis agent, reducing the difficulty of biochemical treatment of ammonia nitrogen in the later stage, and the influence of methanol/sodium methoxide on the crystallization quality of later products; using extraction-oxidation-stripping The purification process ensures the crystallization efficiency of sucralose. After the above steps are used to treat the chlorinated solution containing sucralose-6-acetate, a relatively pure sucralose product can be obtained.

The present application does not limit the equipment used to implement the method provided by the application. Those skilled in the art can choose according to the process flow. Figure 1 shows a schematic structural diagram of the equipment for preparing sucralose according to an embodiment of the application. The equipment given in 1 is for illustrative purposes only and does not limit the application. As shown in 1, the equipment 100 for sucralose shown in FIG. 1 includes: a neutralization reaction rectification tower R-1, a hydrolysis reaction rectification tower R-2, a pH adjustment tank V-1, and a rotating disk extraction tower connected in sequence R-3, oxidation kettle V-2, rotary disk extraction tower R-4, concentration kettle V-3, crystallization kettle V-4 and plate and frame filter press E-1.

Fig. 2 shows a schematic flow chart of a method for preparing sucralose according to an embodiment of the present application. It can be seen from Fig. 2 that the method at least includes steps S210 to S240:

Neutralization step S210: the chlorination reaction solution for preparing sucralose-6 ester, the first liquid caustic soda and the first reused water are put into the neutralization reaction distillation tower in sections, and after the neutralization reaction is carried out under evaporation conditions, the neutralization The solvent mixture is extracted from the top of the reactive distillation tower; the chlorination reaction neutralizing liquid is extracted from the bottom of the neutralized reactive distillation column.

As can be seen from Figure 1, the neutralization reaction rectification tower R-1 includes three feeding sections, the upper section is the chlorination reaction liquid feeding section, the middle section is the first liquid alkali feeding section, and the lower section is the first recycled water Feed section.

The chlorination reaction solution in the present application is a chlorination reaction between sucrose-6-carboxylate and a chlorination reagent, and the resulting mixed solution of reactants is called a chlorination reaction solution. This application is suitable for preparing the reaction solution produced in the chlorination reaction stage of sucralose by various methods in the prior art, such as single-group protection method, multi-group protection method, etc., for the chlorination of sucrose-6-carboxylate The source of the reaction solution is not limited in the present application, and it may be the reaction solution produced in the chlorination reaction stage in the preparation of sucralose in the laboratory or in industrial production.

Due to the use of strong chlorination reagents, such as thionyl chloride and phosgene, during the chlorination reaction, the high temperature in the chlorination insulation stage will produce a series of by-products, such as monochlorosucrose-6-carboxylic acid ester, dichlorosucrose-6-carboxylate, tetrachlorosucrose-6-carboxylate, sucralose diester, etc., also contains some organic impurities such as N,N-dimethylformamide (DMF) and trichloroethane, and large quantities of water.

At present, in the prior art, the neutralization of sucrose-6-carboxylate chlorination reaction solution usually adopts ammonia water or directly adopts ammonia gas, and the use of ammonia water or ammonia gas increases a large amount of nitrogen elements in the system, which is not conducive to Subsequent separation and recovery of waste liquid.

Different from the prior art, in this application, liquid caustic soda is used instead of ammonia water or ammonia gas. In some embodiments of this application, liquid caustic soda can be obtained by dissolving sodium hydroxide and potassium hydroxide in water, or can be directly used Commercially available products, such as 32wt% sodium hydroxide solution.

In this application, due to economical considerations, reused water is used as the water source, which enters from the lower section of the neutralization reaction distillation tower. The reason why the first water is added is that water and DMF are miscible. During the process of evaporating the first water from liquid water to gaseous state, the first water can quickly take out the DMF.

In the neutralization reaction process, the purpose of selecting the upper section of the neutralization reaction rectification tower for the chlorination reaction liquid is to first evaporate and remove the trichloroethane solvent (trichloroethane with a low boiling point) after the material enters the neutralization reaction rectification tower. , 75°C, insoluble in water), the first liquid caustic soda is fed from the middle stage to ensure that the chlorination reaction liquid can be completely neutralized, and the first recycled water is fed from the lower stage to make use of its azeotropic characteristics with DMF to increase the DMF removal efficiency.

The chlorination reaction solution is acidic, and the chlorination reaction solution, the first liquid alkali and the first recycled water undergo a neutralization reaction in the neutralization reaction distillation tower, and the sucralose-6-ester is released. In the prior art Among them, sucralose-6-acetate is the most widely used, and the following is an example of sucralose-6-acetate.

At the same time of the neutralization reaction, the solvent can be removed by evaporation and other means. The solvent is mainly DMF, trichloroethane, and a mixed solvent formed by a large amount of water. In some embodiments of the application, a vacuum pump can be used to reduce the neutralization reaction. The pressure of the rectification column to promote the evaporation of mixed solvents.

After the chlorination reaction solution reacts with the first liquid caustic soda, most of the mixed solvent is removed, and the remaining solution obtained is called chlorination reaction neutralization solution.

Hydrolysis step S220: Make the chlorination reaction neutralization liquid, the second liquid alkali and the second reused water enter the hydrolysis reaction rectification tower in stages, and carry out the alkaline hydrolysis reaction under the evaporation condition, and extract from the top of the hydrolysis reaction rectification tower The waste aqueous solution is extracted, and the sucralose aqueous solution is extracted from the bottom of the hydrolysis reaction distillation tower.

Then make the chlorination reaction neutralizing liquid, the second liquid caustic soda and the second reused water section enter the hydrolysis reaction rectification tower R-2, as can be seen from Fig. 1, the hydrolysis reaction rectification tower R-2 comprises three processes In the feeding section, the upper section is the chlorination reaction neutralization liquid feeding section, the middle section is the second liquid alkali feeding section, and the lower section is the second recycled water feeding section.

In the process of hydrolysis reaction, the purpose of selecting the feed from the upper section of the hydrolysis reaction distillation tower for the chlorination reaction neutralization liquid is to first evaporate and remove the remaining trichloroethane solvent after the material enters the neutralization reaction rectification tower, and the second liquid Alkali is fed from the middle section to ensure that the neutralization liquid in the chlorination reaction can be completely hydrolyzed, and the second reuse water is fed from the lower section to improve the removal efficiency of DMF by utilizing its azeotropic characteristics with DMF.

The chlorination reaction neutralizing liquid is subjected to alkaline hydrolysis reaction in the presence of the second liquid alkali, and in the process of alkaline hydrolysis, evaporation means are used to further evaporate the mixed solvent. After the hydrolysis reaction, sucralose-6- Esters complete hydrolysis to sucralose.

The function of the second recycling water is the same as that of the first recycling water, and the second recycling water and the mixed solvent generate a waste aqueous solution, which can be extracted from the top of the hydrolysis reaction distillation tower.

Through the combination of the neutralization step and the hydrolysis step, the sucralose-6-ester is released from the chlorination reaction solution, and solvents such as DMF and trichloroethane are removed, so that the sucralose-6-ethyl The acid ester is hydrolyzed into sucralose, realizing the continuous operation of neutralization, solvent removal and hydrolysis.

Extraction and purification step S230: After adjusting the sucralose aqueous solution to neutrality, extraction, oxidation and back extraction are performed in sequence for purification.

The obtained sucralose aqueous solution includes but not limited to the target product sucralose, organic ester impurities, incompletely evaporated organic solvents, and alkali ions. Due to the presence of liquid caustic soda, the aqueous solution of sucralose is alkaline and can be adjusted to neutrality with acidic substances. It should be noted that in this application, "neutral" does not mean pH=7 in the strict sense, and pH values around 7, such as pH=6-8, can be considered as neutral. In some embodiments of the present application, the pH value of the sucralose aqueous solution is adjusted to 6-8 by using an inorganic acid, wherein the inorganic acid is one of hydrochloric acid, sulfuric acid or phosphoric acid.

Then, the aqueous solution of sucralose is treated by successively adopting the processes of extraction, oxidation and stripping. Extraction, also known as solvent extraction or liquid-liquid extraction, also known as extraction, is a unit operation that uses the different solubility of the components in the system to separate the mixture; A method in which a solute substance is transferred from one solvent to another due to the difference in solubility or partition coefficient in a slightly soluble solvent. In the present application, the extractant used for extraction is organic ester, such as ethyl acetate and/or butyl acetate, sucralose in aqueous solution, the target product sucralose dissolved in the extractant and sucralose similar in structure The organic ester is extracted into the extractant, the aqueous phase obtained by extraction is sent to waste water treatment, and the obtained organic phase is subjected to subsequent steps.

Then, an oxidizing agent is added to the obtained organic phase. The purpose of the oxidizing agent is to oxidize organic ester impurities such as sucralose tetrachloride to the target product sucralose, thereby achieving the purpose of greatly increasing the yield of sucralose.

After the oxidation reaction is completed, back extraction is carried out. The so-called back extraction is the process of returning the extract from the loaded organic phase to the water phase with a back extraction agent. It is the reverse process of extraction. Through back extraction, the sucralose can be obtained from the extraction process. The organic phase is transferred to the stripping agent. In some embodiments of the present application, water or deionized water can be used as the stripping agent, especially the use of deionized water is more conducive to the subsequent crystallization effect. Through the extraction and purification steps, the purity of the sucralose is ensured, which endows the feasibility of the method.

And crystallization step S240: Concentrate, crystallize and filter the purified sucralose aqueous solution to obtain crude sucralose product and crystallization mother liquor.

Finally, the purified sucralose aqueous solution is subjected to a crystallization step to obtain the crude sucralose product and the remaining primary crystallization mother liquor. For crystallization methods and conditions, reference can be made to the prior art, including but not limited to the use of means such as concentration, crystallization, and filtration to achieve the purpose of crystallization.

And because the stripping agent usually uses water, in the crystallization step, it is actually a water crystallization process, the crystallization process is easier to control, and the crystallization effect is good.

Adopt the preparation equipment of sucralose shown in Fig. 1 to carry out the method provided by the present application and can briefly describe as follows, at first respectively input chlorination reaction liquid, the first liquid alkali And the first back water for neutralization and desolvation operations. DMF is extracted from the top of the tower, and the mixed solvent formed by trichloroethane and water is desolvated and separated, and the neutralization liquid of the chlorination reaction is extracted from the bottom of the tower and input into the lower hydrolysis reaction distillation tower R-2; The upper, middle and lower sections of the tower input the chlorination reaction neutralization liquid, the second liquid caustic soda and the second recycled water for hydrolysis and solvent removal. The mixture formed by extracting a small amount of DMF and water from the top of the tower is used for sewage treatment, and the aqueous solution of sucralose is extracted from the bottom of the tower and input into the lower neutralization reactor V-1; adding inorganic acid to the neutralization reactor V-1 to adjust the pH to neutral properties, and then input to the lower rotary disk extraction tower R-3; in the upper and lower sections of the rotary disk extraction tower R-3, the sucralose aqueous solution and organic ester materials are respectively input as extraction agents, and the trichloro The organic phase of the sucrose extract is extracted from the bottom of the rotary extraction tower R-3 with high brine; the organic phase extract containing sucralose and the oxidant are input into the oxidation kettle V-2 together, and after a period of reaction under certain conditions , into the lower section of the rotary extraction tower R-4; input pure water into the upper section of the rotary disk extraction tower R-4, and extract it countercurrently with the organic phase, and extract the organic phase from the top of the rotary extraction tower R-4 to remove the solvent and recover it. The sucralose solution is extracted from the tower bottom of R-4 to the concentration tank V-3; the sucralose aqueous solution is concentrated in the concentration tank V-3, and the sucralose is concentrated to a certain concentration under certain conditions and then input to the lower crystallization tank V- 4. After the crystallization is completed, the material is input into the plate and frame filter press E-1 for pressure filtration and separation, and the obtained solid is sucralose crystals, and the primary crystallization mother liquor and multiple crystallization mother liquors are returned to the concentration tank V-3 to continue to concentrate, and repeated several times Finally, the final mother liquor is used as waste sugar water for sewage treatment. As can be seen from the method shown in Figure 2, this application uses the untreated chlorinated reaction liquid obtained when preparing sucralose-6-ester as raw material, and uses a neutralization reaction rectification tower to realize the neutralization and precipitation of the chlorinated liquid , and then use the hydrolysis rectification tower to achieve the purpose of desolventization and hydrolysis of sucralose-6-ester to prepare sucralose, and finally through extraction-oxidation-back extraction, the continuous preparation of sucralose is realized. This application abandons The traditional intermittent neutralization, precipitation, hydrolysis, and lengthy sucralose-6-acetate purification process have significantly improved the efficiency of the preparation and purification of sucralose; and compared with the prior art, this application uses liquid Alkali neutralizes the chlorination reaction liquid, abandoning the use of ammonia water and sodium methoxide, on the one hand, it reduces the pressure brought by the ammonia nitrogen content in the later biochemical treatment; on the other hand, it avoids the use and production of methanol, which is environmentally friendly It is a high-efficiency, green and continuous sucralose preparation process with high application value and practicability.

In some embodiments of the present application, the above-mentioned method further includes: a mother liquor recycling step: recycling the crystallization mother liquor into the sucralose aqueous solution to enter the crystallization step, and the recycling times are 1-5 times.

The mother liquor retained after the first crystallization is called the primary crystallization mother liquor. The primary crystallization mother liquor is recrystallized after removing impurities, and the remaining mother liquor after the secondary crystallization is called the secondary crystallization mother liquor. A small amount of crystallization can be obtained after the secondary crystallization mother liquor removes impurities again. Both the secondary crystallization mother liquor and the mother liquor remaining after recrystallization are called multiple crystallization mother liquors.

In some embodiments of the present application, in order to further increase the yield of sucralose, the crystallization mother liquor can be recycled multiple times, so as to crystallize the target product in the mother liquor more thoroughly.

Neutralization reaction distillation column

In this application, there is no limitation on the type of neutralization reaction distillation tower, any distillation tower that can realize neutralization and distillation at the same time is sufficient. In some embodiments, the neutralization reaction distillation tower can be a packed tower or plate type tower.

The packed tower uses packing as the basic component of gas-liquid contact and mass transfer. The liquid flows from top to bottom in the form of a film on the surface of the packing, and the gas flows in a continuous phase from bottom to top with the liquid, and the gas and liquid two Mass and heat transfer between phases. The component concentrations and temperatures of the two phases vary continuously along the height of the column. The packed tower is a differential contact type gas and liquid mass transfer equipment. In some embodiments of the present application, the packing in the packed tower is polytetrafluoro corrugated plate or θ ring, and the packing height is 1/3-2/3 of the height of the packed tower.

Tray tower is a kind of graded contact mass transfer equipment used in gas-liquid or liquid-liquid system. It consists of a cylindrical tower body and a number of trays installed horizontally in the tower at a certain distance. Widely used in rectification and absorption, some types (such as sieve plate column) are also used for extraction, and can also be used as a reactor for gas-liquid phase reaction process. During operation (take the gas-liquid system as an example), the liquid flows through each layer of trays from top to bottom in sequence under the action of gravity, and is discharged from the bottom of the tower; the gas is pushed through the layers from bottom to top under the push of pressure difference Tray plate, to the top of the tower to discharge. A certain depth of liquid layer is maintained on each tray, and the gas is dispersed into the liquid layer through the tray for interphase contact and mass transfer.

In this application, the specifications of the neutralization reaction distillation tower are not limited. In some embodiments, considering the effect of the neutralization reaction, the tower height of the neutralization reaction distillation tower is 10-30m; wherein, the chlorination reaction The liquid feeding position is at a position of 3/10 to 2/5 of the tower height from the top of the tower, and the feeding position of the first liquid caustic soda is at a position of 1/2 to 3/5 of the tower height from the top of the tower. The feeding position of the recycled water is 7/10-4/5 of the height of the tower from the top of the tower.

neutralization reaction conditions

In the present application, the reaction conditions of the neutralization reaction are not limited, as long as the neutralization reaction can be carried out thoroughly, in some embodiments of the application, considering the reaction effect of the neutralization reaction, the neutralization reaction rectification The tower top temperature of the tower is set at 30-40°C, and the tower bottom temperature is set at 50-60°C.

Hydrolysis reaction distillation column

In this application, there is no limitation on the type of the hydrolysis reaction distillation column, any distillation column that can realize hydrolysis and distillation at the same time is sufficient. In some embodiments, the hydrolysis reaction distillation column can be a packed column or a tray column.

In this application, the specifications of the hydrolysis reaction distillation tower are not limited. In some embodiments, considering the effect of the hydrolysis reaction, the tower height of the hydrolysis reaction distillation tower is 10-30m; wherein, the chlorination liquid neutralizing liquid The feeding position is at a position of 2/5 to 3/7 of the tower height from the top of the tower, and the feeding position of the second liquid caustic soda is at a position of 1/2 to 3/5 of the tower height from the top of the tower. The feeding position of water is at a position of 4/5-9/10 of the tower height from the top of the tower.

Hydrolysis reaction conditions

In the present application, the conditions of the hydrolysis reaction are not limited, but the hydrolysis can be carried out thoroughly. In some embodiments, in consideration of the hydrolysis effect, when the hydrolysis reaction is carried out, the temperature at the top of the neutralization reaction distillation tower is set to 30-40°C, and the temperature at the bottom of the tower is set at 50-60°C.

The material ratio of the chlorination reaction liquid, the first liquid caustic soda and the first recycled water

In the present application, in the neutralization step, there is no limitation to the material ratio of the chlorination reaction liquid, the first liquid alkali and the first recycled water. In some embodiments, the chlorination reaction liquid, the first liquid alkali and the second The volume ratio of primary water is 10-15:1:1. In the above material ratio, neutralization can be carried out completely, and most of the solvent can be taken out by the primary water without waste of raw materials.

The material ratio of chlorination reaction neutralizing liquid, second liquid caustic soda and second recycled water

In the present application, in the hydrolysis step, there is no limitation on the material ratio of the chlorination reaction neutralizing liquid, the second liquid alkali and the second recycled water. In some embodiments, the chlorination reaction neutralizing liquid, the second liquid The volume ratio of the alkali to the second water is 40-60:1:10-20. In the above material ratio, the hydrolysis can be carried out completely, and most of the solvent can be taken out by the second water without causing Raw material wastage.

The type and amount of extractant

In the present application, in the extraction and purification step, in order to extract sucralose, an organic ester can be selected as the extractant, such as ethyl acetate and/or butyl acetate.

In some embodiments of the present application, the amount of extractant is not limited, it can be determined according to the amount of chlorination reaction neutralization liquid, such as the ratio of the volume of extraction agent to chlorination reaction neutralization liquid is 1 to 5:1 , within the range of the above-mentioned dosage ratio, the extraction can achieve a better technical effect without causing waste of the extractant.

Type and amount of oxidizing agent

In some embodiments of the present application, the oxidizing agent is screened, and it is found that sodium hypochlorite or ozone is used for selection, and the selective oxidation is relatively good, that is, tetrachlorosucrose can be oxidized to sucralose, and simultaneously Does not further oxidize sucralose.

In some embodiments of the present application, the mass fraction and dosage of the oxidizing agent are not limited. In other embodiments, when the oxidizing agent is sodium hypochlorite, the mass dosage of sodium hypochlorite is 0.01% to 0.1% of the volume of the extracted organic phase; When the oxidizing agent is ozone, the volumetric dosage of ozone is 0.01-0.1% of the volume of the organic phase obtained by extraction. If the amount of oxidizing agent is less than the lower limit of the above range, the amount is too small, the oxidation reaction is not carried out thoroughly, affecting the yield of sucralose; if the amount of oxidizing agent is greater than the upper limit of the above range, then the amount is too much, may cause excessive oxidation.

Oxidation reaction conditions

In some embodiments of the present application, the oxidation temperature and oxidation time of the oxidation reaction are not limited, and in other embodiments, the oxidation time of oxidation is 3-12 hours; the oxidation temperature can be at room temperature.

The amount of stripping agent

In some embodiments of the present application, the amount of stripping agent is not limited, and can be determined according to the amount of neutralizing liquid in the chlorination reaction, such as the ratio of the volume of stripping agent to the volume of the organic phase obtained by extraction is 1 ~ 5:1. Within the range of the above-mentioned dosage ratio, the stripping can achieve better technical effect without causing waste of stripping agent.

crystallization conditions

In some embodiments of the present application, the crystallization conditions are not limited, and one or more combinations of the prior art may be referred to. In other embodiments, in the crystallization step, the concentrated concentration temperature is 40-60 °C, the vacuum degree of concentration is -0.1～-0.5Mpa, and the concentration of sucralose in the sucralose aqueous solution is 80～140g/L.

Test methods involved in this application

In each embodiment and comparative example in the application, each material content adopts the high performance liquid chromatography (High Performance Liquid Chromatography, HPLC) method to adopt the external standard method to record under the following conditions, no longer repeat them in each embodiment.

Analysis and determination conditions of high performance liquid chromatography: Japan Shimadzu high performance liquid chromatography, equipped with RID-10A differential refraction detection, LC-10ADVP high pressure pump, CTO-10ASVP constant temperature box; chromatographic column: Agilent XDB C18 column (250mm×4.6mm , 5 μm); mobile phase: methanol-0.125% dipotassium hydrogen phosphate aqueous solution (4:6); column temperature: 40°C; flow rate: 1.0mL/min. Among them, methanol (chromatographically pure), dipotassium hydrogen phosphate (analytical pure), ultrapure water, etc. are required, and each standard substance is measured by an external standard method.

Example 1

Neutralization step: The neutralization reaction distillation tower R-1 is a packed tower with a tower height of 10m, and the packing is polytetrafluoro corrugated board, and the packing height is 1/3 of the tower height. The chlorination reaction liquid, the first liquid caustic soda, and the first recycled water are respectively input into the neutralization reaction distillation tower at positions 3m, 5m, and 7m away from the tower top. The temperature at the top of the neutralization reaction distillation column R-1 is 30°C, and the temperature at the bottom of the column is 50°C. The material feed ratio (volume ratio) is chlorination reaction solution: the first caustic soda: the first water = 10:1:1, and the first caustic is 32% (mass percentage, commercially available) NaOH aqueous solution. The mixed solvent is extracted from the top of the neutralization reactive distillation tower R-1 for separation, and the chlorination reaction neutralization liquid extracted from the bottom of the neutralization reactive distillation tower R-1 is input into the hydrolysis reactive distillation tower R-2.

Hydrolysis step: the hydrolysis reaction rectification tower R-2 is a plate tower with a tower height of 10m, and the filler is a stainless steel θ ring, and the height of the filler is 1/3 of the height of the tower; Reuse water is input into the hydrolysis reaction distillation tower R-2 at the positions of 4m, 5m and 8m from the top of the tower respectively. The temperature at the top of the hydrolysis reaction distillation column is 30°C, and the temperature at the bottom of the column is 50°C. The material feed ratio (volume ratio) is chlorination reaction neutralizing liquid: the second liquid caustic soda: the second recycled water = 40:1:10, and the second liquid caustic is 32% (mass percentage, commercially available) NaOH. The waste water is extracted from the top of the tower for sewage treatment, and the sucralose aqueous solution is extracted from the bottom of the tower and input into the pH adjustment kettle V-1.

Extraction step: add hydrochloric acid to the pH adjustment kettle V-1 to adjust the pH to 6, then input the material to the upper section of the rotary extraction tower R-3, and input the ethyl acetate extractant from the rotary disk extraction tower R-3, and the extraction ratio is ( Volume ratio) ethyl acetate: chlorination reaction neutralizing solution=5:1. After the extraction is completed, the water phase is output from the lower section of the rotary disk extraction tower R-3 for high-salt wastewater treatment, and the ethyl acetate phase is output from the upper section and enters the oxidation tank V-2 for oxidation treatment. Add 0.01% ozone by volume of the ethyl acetate phase into the oxidation kettle V-2, oxidize for 10 h, and then input the reaction liquid obtained by oxidation into the lower section of the rotary disk extraction tower R-4. Pure water is input from the upper part of the rotary disk extraction tower R-4, and the stripping ratio is (volume ratio) water: ethyl acetate phase = 1:1. After the stripping is completed, ethyl acetate is extracted from the top of the rotary disk extraction tower R-4 to remove the solvent for recovery, and the aqueous sucralose solution extracted in the lower section is input into the concentration tank V-3.

Crystallization step: input the sucralose aqueous solution into the concentration tank V-3 for concentration, the concentration temperature is 40°C, the vacuum degree is -0.1Mpa, the concentrated sucralose concentration is 80g/L, and then the concentrated solution is input into the crystallization tank V-4 Crystallization at room temperature, sucralose mother liquor was reused 4 times, and the purity of sucralose after drying is shown in Table 1.

Table 1 Sucralose Product Purity

Mother liquor reuse times	Product purity/%	Water content/wt%
0	99.87	0.13
1	99.75	0.25
2	99.89	0.11
3	99.90	0.10
4	99.82	0.18

Example 2

Neutralization step: The neutralization reaction distillation tower R-1 is a packed tower with a tower height of 15m, and the packing is polytetrafluorotheta ring, and the packing height is 1/2 of the tower height. The chlorination reaction liquid, the first liquid caustic soda, and the first reused water are respectively input into the neutralization reaction distillation column R-1 at positions 6m, 9m, and 12m away from the tower top. The temperature at the top of the neutralization reaction distillation column R-1 is 35°C, and the temperature at the bottom of the column is 55°C. The ratio of material to feed (volume ratio) is chlorination reaction solution: first liquid alkali: first water = 11:1:1, and the first liquid alkali is 32% (mass percentage, commercially available) KOH. The mixed solvent is extracted from the top of the neutralization reaction rectification tower R-1 for separation, and the neutralization liquid of the chlorination reaction at the bottom of the tower is input into the hydrolysis reaction rectification tower R-2.

Hydrolysis step: the hydrolysis reaction rectification tower R-2 is a plate tower with a tower height of 15m, and the packing is stainless steel corrugated plate, and the packing height is 1/3 of the tower height; The secondary water is input into the hydrolysis reaction distillation column R-2 at positions 6.5m, 9m, and 13.5m from the top of the tower respectively. The temperature at the top of the hydrolysis reaction distillation column R-2 is 35°C, and the temperature at the bottom of the column is 55°C. The material feed ratio (volume ratio) is chlorination reaction neutralizing liquid: the second liquid caustic soda: the second recycled water = 50:1:15, and the second liquid caustic is 32% (mass percentage, commercially available) KOH. The waste water is extracted from the top of the hydrolysis reaction distillation column R-2 for sewage treatment, and the sucralose aqueous solution is extracted from the bottom of the column and input into the pH adjustment tank V-1.

Extraction step: add sulfuric acid to the pH adjustment kettle V-1 to adjust the pH to 7, then input the material to the upper section of the rotary extraction tower R-3, and input the ethyl acetate extractant from the rotary disk extraction tower R-3, and the extraction ratio is ( Volume ratio) ethyl acetate: chlorination reaction neutralizing solution=4:1. After the extraction is completed, the water phase is output from the lower section of the rotary disk extraction tower R-3 for high-salt wastewater treatment, and the ethyl acetate phase is output from the upper section into the oxidation tank V-2 for oxidation treatment. Add 0.1% ozone in ethyl acetate phase volume to the oxidation kettle V-2, oxidize for 3 hours, and then input the reaction liquid obtained by oxidation into the lower section of the rotary disk extraction tower R-4. Pure water is input from the upper part of the rotary disk extraction tower R-4, and the stripping ratio is (volume ratio) water: ethyl acetate phase = 5:1. After the stripping is completed, ethyl acetate is taken from the top of the rotary disk extraction tower R-4 to remove the solvent for recovery, and the sucralose aqueous solution is taken from the lower section and input into the concentration tank V-3.

Crystallization step: input the sucralose aqueous solution into the concentration tank V-3 for concentration, the concentration temperature is 60°C, the vacuum degree is -0.05Mpa, the concentrated sucralose concentration is 100g/L, and then the concentrated solution is input into the crystallization tank V-4 Crystallization at room temperature, sucralose mother liquor was reused 4 times, and the purity of sucralose after drying is shown in Table 2.

Table 2 Sucralose Product Purity

Mother liquor reuse times	Product purity/%	Water content/wt%
0	99.91	0.09
1	99.93	0.07
2	99.90	0.10
3	99.80	0.20
4	99.84	0.16

Example 3

Neutralization step: The neutralization reaction distillation tower R-1 is a packed tower with a tower height of 20m, and the packing is polytetrafluoro corrugated board, and the packing height is 2/3 of the tower height. The chlorination reaction liquid, the first liquid caustic soda, and the first reused water are respectively input into the neutralization reaction distillation column R-1 at positions 7m, 11m, and 15m away from the tower top. The temperature at the top of the neutralization reaction distillation column R-1 is 40°C, and the temperature at the bottom of the column is 55°C. The ratio of material to feed (volume ratio) is chlorination reaction solution: first liquid caustic soda: first water = 15:1:1, and the first liquid caustic is 32% (mass percentage, commercially available) NaOH. The mixed solvent is taken from the top of the neutralization reaction distillation tower R-1 for separation, and the neutralization liquid from the chlorination reaction is taken from the bottom of the tower and input into the hydrolysis reaction distillation tower R-2.

Hydrolysis step: the hydrolysis reaction rectification tower R-2 is a plate tower with a tower height of 20m, and the packing is stainless steel corrugated plate, and the packing height is 2/3 of the tower height; The secondary water is input into the hydrolysis reaction distillation tower R-2 at the positions of 8.2m, 11m and 17m from the top of the tower respectively. The temperature at the top of the hydrolysis reaction distillation column R-2 is 35°C, and the temperature at the bottom of the column is 60°C. The ratio of material to feed (volume ratio) is chlorination reaction neutralizing liquid: second liquid caustic soda: second recycled water = 60:1:20, and the second liquid caustic is 32% (mass percentage, commercially available) KOH. The tower top of the hydrolysis reaction rectification tower R-2 extracts waste water for sewage treatment, and extracts the sucralose aqueous solution from the tower bottom to input the pH adjustment kettle V-1.

Extraction step: add phosphoric acid to the pH adjustment kettle V-1 to adjust the pH to 6.5, then input the material to the upper section of the rotary extraction tower R-3, and input the ethyl acetate extractant from the rotary disk extraction tower R-3, and the extraction ratio is ( Volume ratio) ethyl acetate: chlorination reaction neutralizing solution=1:1. After the extraction is completed, the water phase is output from the lower section of the rotary disk extraction tower R-3 for high-salt wastewater treatment, and the ethyl acetate phase is output from the upper section into the oxidation tank V-2 for oxidation treatment. Add sodium hypochlorite with an ethyl acetate phase volume of 0.01% to the oxidation kettle V-2, oxidize for 12 hours, and then input the reaction liquid obtained by oxidation into the lower section of the rotary disk extraction tower R-4. Pure water is input from the upper part of the rotary disk extraction tower R-4, and the stripping ratio is (volume ratio) water: ethyl acetate phase = 3:1. After the stripping is completed, ethyl acetate is taken from the top of the rotary disk extraction tower R-4 to remove the solvent for recovery, and the sucralose aqueous solution is taken from the lower section and input into the concentration tank V-3.

Crystallization step: input the sucralose aqueous solution into the concentration tank V-3 for concentration, the concentration temperature is 50°C, the vacuum degree is -0.07Mpa, the concentrated sucralose concentration is 120g/L, and then the concentrated solution is input into the crystallization tank V-4 Crystallization at room temperature, sucralose mother liquor was reused 5 times, and the purity of sucralose after drying is shown in Table 3.

Table 3 Sucralose Product Purity

Mother liquor reuse times	Product purity/%	Water content/wt%
0	99.82	0.18
1	99.85	0.15
2	99.85	0.15
3	99.80	0.20
4	99.78	0.22
5	99.77	0.23

Example 4

Neutralization step: The neutralization reaction distillation tower R-1 is a packed tower with a tower height of 25m, and the packing is polytetrafluorotheta ring, and the packing height is 3/5 of the tower height. The chlorination reaction liquid, the first liquid caustic soda, and the first reused water are respectively input into the neutralization reaction distillation column R-1 at positions 8m, 13m, and 18m away from the tower top. The temperature at the top of the neutralization reaction distillation column R-1 is 33°C, and the temperature at the bottom of the column is 58°C. The ratio of material to feed (volume ratio) is chlorination reaction liquid: first liquid alkali: first water = 13:1:1, and the first liquid alkali is 32% (mass percentage, commercially available) KOH. The mixed solvent is taken from the top of the neutralization reaction distillation tower R-1 for separation, and the neutralization liquid from the chlorination reaction is taken from the bottom of the tower and input into the hydrolysis reaction distillation tower R-2.

Hydrolysis step: the hydrolysis reaction distillation tower R-2 is a plate tower with a tower height of 25m, and the filler is a stainless steel θ ring, and the height of the filler is 1/3 of the height of the tower; The secondary water is input into the hydrolysis reaction distillation tower R-2 at the positions of 10.5m, 13m and 20.5m from the top of the tower respectively. The temperature at the top of the hydrolysis reaction distillation column R-2 was 32°C, and the temperature at the bottom of the column was 56°C. The material feed ratio (volume ratio) is chlorination reaction neutralizing liquid: the second liquid caustic soda: the second recycled water = 45:1:10, and the second liquid caustic is 32% (mass percentage, commercially available) NaOH. The waste water is extracted from the top of the hydrolysis reaction distillation column R-2 for sewage treatment, and the sucralose aqueous solution is extracted from the bottom of the column and input into the pH adjustment tank V-1.

Extraction step: add hydrochloric acid to the pH adjustment kettle V-1 to adjust the pH to 8, then input the material to the upper section of the rotary extraction tower R-3, and input the ethyl acetate extractant from the rotary disk extraction tower R-3, and the extraction ratio is ( Volume ratio) ethyl acetate: chlorination reaction neutralizing solution=2:1. After the extraction is completed, the water phase is output from the lower section of the rotary disk extraction tower R-3 for high-salt wastewater treatment, and the ethyl acetate phase is output from the upper section into the oxidation tank V-2 for oxidation treatment. Add 0.1% of the ethyl acetate phase volume of ozone into the oxidation kettle V-2, oxidize for 4 hours, and then input the reaction solution obtained from the oxidation into the lower section of the rotary disk extraction tower R-4. Pure water is input from the upper part of the rotary disk extraction tower R-4, and the stripping ratio is (volume ratio) water: ethyl acetate phase = 5:1. After the stripping is completed, ethyl acetate is taken from the top of the rotary disk extraction tower R-4 to remove the solvent for recovery, and the sucralose aqueous solution is taken from the lower section and input into the concentration tank V-3.

Crystallization step: input the sucralose aqueous solution into the concentration tank V-3 for concentration, the concentration temperature is 45°C, the vacuum degree is -0.09Mpa, the concentrated sucralose concentration is 110g/L, and then the concentrated solution is input into the crystallization tank V-4 Crystallization at room temperature, sucralose mother liquor was reused 5 times, and the purity of sucralose after drying is shown in Table 4.

Table 4 Sucralose Product Purity

Mother liquor reuse times	Product purity/%	Water content/wt%
0	99.89	0.11
1	99.85	0.15
2	99.91	0.09
3	99.93	0.07
4	99.90	0.10
5	99.83	0.17

Example 5

Neutralization step: The neutralization reaction distillation tower R-1 is a packed tower with a tower height of 30m, and the packing is polytetrafluorotheta ring, and the packing height is 1/3 of the tower height. The chlorination reaction liquid, the first liquid caustic soda, and the first reused water are respectively input into the neutralization reactive distillation column R-1 at positions 10.2m, 16.2m, and 22.2m away from the tower top. The temperature at the top of the neutralization reaction distillation column R-1 is 40°C, and the temperature at the bottom of the column is 60°C. The ratio of material to feed (volume ratio) is chlorination reaction liquid: the first caustic soda: the first water = 13:1:1, and the first caustic is 32% (mass percentage, commercially available) NaOH. The mixed solvent is taken from the top of the neutralization reaction distillation tower R-1 for separation, and the neutralization liquid from the chlorination reaction is taken from the bottom of the tower and input into the hydrolysis reaction distillation tower R-2.

Hydrolysis step: the hydrolysis reaction rectification tower R-2 is a plate tower with a tower height of 30m, and the packing is stainless steel corrugated plate, and the packing height is 3/5 of the tower height; The recycled water is input into the hydrolysis reaction distillation tower R-2 at the positions of 12.3m, 16.2m and 25.2m from the top of the tower respectively. The temperature at the top of the hydrolysis reaction distillation column R-2 is 40°C, and the temperature at the bottom of the column is 60°C. The material feed ratio (volume ratio) is chlorination reaction neutralizing liquid: the second liquid caustic soda: the second recycled water = 55:1:12, and the second liquid caustic is 32% (mass percentage, commercially available) NaOH. The waste water is extracted from the top of the hydrolysis reaction distillation column R-2 for sewage treatment, and the sucralose aqueous solution is extracted from the bottom of the column and input into the pH adjustment tank V-1.

Extraction step: add sulfuric acid to the pH adjustment kettle V-1 to adjust the pH to 7.5, then input the material to the upper section of the rotary extraction tower R-3, and input the ethyl acetate extractant from the rotary disk extraction tower R-3, and the extraction ratio is ( Volume ratio) ethyl acetate: chlorination reaction neutralizing solution=4:1. After the extraction is completed, the water phase is output from the lower section of the rotary disk extraction tower R-3 for high-salt wastewater treatment, and the ethyl acetate phase is output from the upper section into the oxidation tank V-2 for oxidation treatment. Add 0.05% of the ethyl acetate phase volume of ozone into the oxidation kettle V-2, oxidize for 6 hours, and then input the reaction solution obtained by oxidation into the lower section of the rotary disk extraction tower R-4. Pure water is input from the upper part of the rotary disk extraction tower R-4, and the stripping ratio is (volume ratio) water: ethyl acetate phase = 3:1. After the stripping is completed, ethyl acetate is taken from the top of the rotary disk extraction tower R-4 to remove the solvent for recovery, and the sucralose aqueous solution is taken from the lower section and input into the concentration tank V-3.

Crystallization step: input the sucralose aqueous solution into the concentration tank V-3 for concentration, the concentration temperature is 55°C, the vacuum degree is -0.06Mpa, the concentrated sucralose concentration is 140g/L, and then the concentrated solution is input into the crystallization tank V-4 Crystallization at room temperature, sucralose mother liquor was reused 4 times, and the purity of sucralose after drying is shown in Table 5.

Table 5 Sucralose Product Purity

Mother liquor reuse times	Product purity/%	Water content/wt%
0	99.95	0.05
1	99.89	0.11
2	99.79	0.21
3	99.86	0.14
4	99.85	0.15

Example 6

Neutralization step: The neutralization reaction distillation tower R-1 is a packed tower with a tower height of 16m, and the packing is polytetrafluoro corrugated board, and the packing height is 2/3 of the tower height. The chlorination reaction liquid, the first liquid caustic soda, and the first recycled water are respectively input into the neutralization reaction distillation column R-1 at positions 6.2m, 9.5m, and 12.9m away from the tower top. The temperature at the top of the neutralization reaction distillation column R-1 is 38°C, and the temperature at the bottom of the column is 52°C. The ratio of materials to feed (volume ratio) is chlorination reaction liquid: the first caustic soda: the first water = 14:1:1, and the first caustic is 32% (mass percentage, commercially available) KOH. The mixed solvent is taken from the top of the neutralization reaction distillation tower R-1 for separation, and the neutralization liquid from the chlorination reaction is taken from the bottom of the tower and input into the hydrolysis reaction distillation tower R-2.

Hydrolysis step: the hydrolysis reaction distillation tower R-2 is a plate tower with a tower height of 16m, and the filler is a stainless steel θ ring, and the height of the filler is 3/5 of the height of the tower; The recycled water is input into the hydrolysis reaction distillation tower R-2 at the positions of 7.8m, 9.5m and 14.6m from the top of the tower respectively. The temperature at the top of the hydrolysis reaction distillation column R-2 is 34°C, and the temperature at the bottom of the column is 57°C. The material feed ratio (volume ratio) is chlorination reaction neutralizing liquid: the second liquid caustic soda: the second recycled water = 41:1:19, and the second liquid caustic is 32% (mass percentage, commercially available) NaOH. The waste water is extracted from the top of the hydrolysis reaction distillation column R-2 for sewage treatment, and the sucralose aqueous solution is extracted from the bottom of the column and input into the pH adjustment tank V-1.

Extraction step: add sulfuric acid to the pH adjustment kettle V-1 to adjust the pH to 7, then input the material to the upper section of the rotary extraction tower R-3, and input the ethyl acetate extractant from the rotary disk extraction tower R-3, and the extraction ratio is ( Volume ratio) ethyl acetate: chlorination reaction neutralizing solution=1:1. After the extraction is completed, the water phase is output from the lower section of the rotary disk extraction tower R-3 for high-salt wastewater treatment, and the ethyl acetate phase is output from the upper section into the oxidation tank V-2 for oxidation treatment. Add sodium hypochlorite with an ethyl acetate phase volume of 0.03% to the oxidation kettle V-2, oxidize for 8 hours, and then input the reaction solution obtained by oxidation into the lower section of the rotary disk extraction tower R-4. Pure water is input from the upper part of the rotary disk extraction tower R-4, and the stripping ratio is (volume ratio) water: ethyl acetate phase = 5:1. After the stripping is completed, the top of the rotary disk extraction tower R-4 extracts ethyl acetate to remove the solvent for recovery, and extracts the sucralose aqueous solution from the lower section to enter the concentration tank V-3.

Crystallization step: input the sucralose aqueous solution into the concentration tank V-3 for concentration, the concentration temperature is 60°C, the vacuum degree is -0.05Mpa, the concentrated sucralose concentration is 140g/L, and then the concentrated solution is input into the crystallization tank V-4 Crystallization at room temperature, sucralose mother liquor was reused 5 times, and the purity of sucralose after drying is shown in Table 6.

Table 6 Sucralose Product Purity

Mother liquor reuse times	Product purity/%	Water content/%
0	99.82	0.18
1	99.88	0.12
2	99.81	0.19
3	99.89	0.11
4	99.92	0.08
5	99.93	0.07

Example 7

Neutralization step: The neutralization reaction distillation tower R-1 is a packed tower with a tower height of 28m. The packing is polytetrafluorotheta ring, and the packing height is 1/3 of the tower height. The chlorination reaction liquid, the first liquid caustic soda, and the first recycled water are respectively input into the neutralization reactive distillation column R-1 at positions 8.4m, 15.4m, and 20.2m away from the tower top. The temperature at the top of the neutralization reaction distillation column R-1 is 39°C, and the temperature at the bottom of the column is 56°C. The ratio of material to feed (volume ratio) is chlorination reaction solution: first liquid alkali: first water = 11:1:1, and the first liquid alkali is 32% (mass percentage, commercially available) NaOH. The mixed solvent is taken from the top of the neutralization reaction distillation tower R-1 for separation, and the neutralization liquid from the chlorination reaction is taken from the bottom of the tower and input into the hydrolysis reaction distillation tower R-2.

Hydrolysis step: the hydrolysis reaction distillation tower R-2 is a plate tower with a tower height of 28m, and the filler is a stainless steel θ ring, and the height of the filler is 2/5 of the height of the tower; Reuse water is input into the hydrolysis reaction distillation tower R-2 at the positions of 11.2m, 16m and 23.8m from the top of the tower respectively. The temperature at the top of the hydrolysis reaction distillation column R-2 is 30°C, and the temperature at the bottom of the column is 51°C. The material feed ratio (volume ratio) is chlorination reaction neutralizing liquid: the second liquid caustic soda: the second recycled water = 58:1:11, and the second liquid caustic is 32% (mass percentage, commercially available) NaOH. The waste water is extracted from the top of the hydrolysis reaction distillation column R-2 for sewage treatment, and the sucralose aqueous solution is extracted from the bottom of the column and input into the pH adjustment tank V-1.

Extraction step: add hydrochloric acid to the pH adjustment kettle V-1 to adjust the pH to 8, then input the material to the upper section of the rotary extraction tower R-3, and input the ethyl acetate extractant from the rotary disk extraction tower R-3, and the extraction ratio is ( Volume ratio) ethyl acetate: chlorination reaction neutralizing solution=2:1. After the extraction is completed, the water phase is output from the lower section of the rotary disk extraction tower R-3 for high-salt wastewater treatment, and the ethyl acetate phase is output from the upper section into the oxidation tank V-2 for oxidation treatment. Add 0.07% of the ethyl acetate phase volume of ozone into the oxidation kettle V-2, oxidize for 5 hours, and then input the reaction solution obtained by oxidation into the lower section of the rotary disk extraction tower R-4. Pure water is input from the upper part of the rotary disk extraction tower R-4, and the stripping ratio is (volume ratio) water: ethyl acetate phase = 3:1. After the stripping is completed, ethyl acetate is taken from the top of the rotary disk extraction tower R-4 to remove the solvent for recovery, and the sucralose aqueous solution is taken from the lower section and input into the concentration tank V-3.

Crystallization step: input the sucralose aqueous solution into the concentration tank V-3 for concentration, the concentration temperature is 50°C, the vacuum degree is -0.08Mpa, the concentrated sucralose concentration is 130g/L, and then the concentrated solution is input into the crystallization tank V-4 Crystallization at room temperature, sucralose mother liquor was reused 4 times, and the purity of sucralose after drying is shown in Table 7.

Table 7 Sucralose Product Purity

Mother liquor reuse times	Product purity/%	Water content/wt%
0	99.77	0.23
1	99.79	0.21
2	99.88	0.12
3	99.83	0.17
4	99.89	0.11

Example 8

Neutralization step: The neutralization reaction distillation tower R-1 is a packed tower with a tower height of 22m, and the packing is polytetrafluoro corrugated board, and the packing height is 2/5 of the tower height. The chlorination reaction liquid, the first liquid caustic soda, and the first recycled water are respectively input into the neutralization reaction distillation column R-1 at positions 8.8m, 11m, and 17m away from the tower top. The temperature at the top of the neutralization reaction distillation column R-1 is 36°C, and the temperature at the bottom of the column is 59°C. The ratio of material to feed (volume ratio) is chlorination reaction solution: first liquid alkali: first water = 15:1:1, and the first liquid alkali is 32% (mass percentage, commercially available) KOH. The mixed solvent is taken from the top of the neutralization reaction distillation tower R-1 for separation, and the neutralization liquid from the chlorination reaction is taken from the bottom of the tower and input into the hydrolysis reaction distillation tower R-2.

Hydrolysis step: the hydrolysis reaction rectification tower R-2 is a plate tower with a tower height of 22m, and the packing is stainless steel corrugated plate, and the packing height is 2/3 of the tower height; The recycled water is input into the hydrolysis reaction distillation tower R-2 at the positions of 9m, 12m and 19m from the top of the tower respectively. The temperature at the top of the hydrolysis reaction distillation column R-2 is 33°C, and the temperature at the bottom of the column is 58°C. The material feed ratio (volume ratio) is chlorination reaction neutralizing liquid: the second liquid caustic soda: the second recycled water = 45:1:18, and the second liquid caustic is 32% (mass percentage, commercially available) KOH. The waste water is extracted from the top of the hydrolysis reaction distillation column R-2 for sewage treatment, and the sucralose aqueous solution is extracted from the bottom of the column and input into the pH adjustment tank V-1.

Extraction step: add phosphoric acid to the pH adjustment kettle V-1 to adjust the pH to 6.5, then input the material to the upper section of the rotary extraction tower R-3, and input the ethyl acetate extractant from the rotary disk extraction tower R-3, and the extraction ratio is ( Volume ratio) ethyl acetate: chlorination reaction neutralizing solution=1:1. After the extraction is completed, the water phase is output from the lower section of the rotary disk extraction tower R-3 for high-salt wastewater treatment, and the ethyl acetate phase is output from the upper section into the oxidation tank V-2 for oxidation treatment. Add sodium hypochlorite with an ethyl acetate phase volume of 0.06% to the oxidation kettle V-2, oxidize for 7 hours, and then input the reaction solution obtained by oxidation into the lower section of the rotary disk extraction tower R-4. Pure water is input from the upper part of the rotary disk extraction tower R-4, and the stripping ratio is (volume ratio) water: ethyl acetate phase = 4:1. After the stripping is completed, ethyl acetate is taken from the top of the rotary disk extraction tower R-4 to remove the solvent for recovery, and the sucralose aqueous solution is taken from the lower section and input into the concentration tank V-3.

Crystallization step: input the sucralose aqueous solution into the concentration tank V-3 for concentration, the concentration temperature is 55°C, the vacuum degree is -0.1Mpa, the concentrated sucralose concentration is 125g/L, and then the concentrated solution is input into the crystallization tank V-4 Crystallization at room temperature, sucralose mother liquor was reused 4 times, and the purity of sucralose after drying is shown in Table 8.

Table 8 Sucralose Product Purity

Mother liquor reuse times	Product purity/%	Water content/wt%
0	99.82	0.18
1	99.85	0.15
2	99.79	0.21
3	99.91	0.09
4	99.83	0.17

Comparative example 1

At present, the existing process for preparing sucralose from sucralose-6-acetate is a batch process, which mainly neutralizes the chlorinated liquid, then purifies to obtain sucralose-6-acetate, and then uses sucralose-6- Pure acetate as raw material is hydrolyzed into sucralose in a sodium methoxide/methanol system, and finally purified to obtain fine sucralose.

Cool 3t of the chlorinated solution to 0°C, then add ammonia water to it, the temperature does not exceed 30°C, adjust the pH to 10.5, keep it warm for 1 hour, then add dilute hydrochloric acid to adjust the pH to neutral. The neutralized chlorinated neutralization solution is heated under reduced pressure and concentrated to dry to remove the organic solvent, and then dissolved in pure water to form a concentrated dry aqueous solution. Ethyl acetate is added to the concentrated dry aqueous solution for extraction, the water phase after extraction is used for wastewater treatment, the ester phase is concentrated until the content of sucralose-6-acetate is greater than 20wt%, and the temperature is cooled to crystallize to obtain sucralose-6-acetate The crude product is then further crystallized with ethyl acetate and water respectively to obtain the fine product of sucralose-6-acetate with a content of about 90% and a water content of about 10%.

Sucralose-6-acetate refined product is used as raw material, sodium methoxide/methanol is added to it for hydrolysis, after hydrolysis is completed, it is extracted with butyl acetate, then the ester phase is concentrated to dryness, after concentration is dried, it is dissolved in water and concentrated to three When the concentration of sucralose reaches 20wt%, it crystallizes at room temperature, repeats twice, and applies the mother liquor 4 times. The purity of sucralose after drying is shown in Table 9.

Table 9 Sucralose Product Purity

Mother liquor reuse times	Product purity/%	Water content/wt%
0	99.60	0.40
1	99.57	0.43
2	99.55	0.45
3	99.50	0.50
4	99.51	0.49

It can be seen from Examples 1 to 8 that the production of sucralose by the method of the present application has a high degree of continuity and good stability, the purity of the sucralose is above 99%, and the water content is very small.

In summary, this application uses the untreated chlorinated reaction liquid obtained during the preparation of sucralose-6-ester as a raw material, and uses a neutralization reaction rectification tower to achieve neutralization and precipitation of the chlorinated liquid, and then uses hydrolytic rectification The tower achieves the purpose of desolvation and hydrolysis of sucralose-6-ester to prepare sucralose, and finally through extraction-oxidation-back extraction, the continuous preparation of sucralose is realized. This application abandons the traditional batch neutralization, Precipitation, hydrolysis, and lengthy sucralose-6-acetate purification process significantly improved the efficiency of the preparation and purification of sucralose; For neutralization, the use of ammonia water and sodium methoxide is discarded. On the one hand, it reduces the pressure brought by the ammonia nitrogen content in the later biochemical treatment; on the other hand, it avoids the use and production of methanol, and is highly environmentally friendly. It is a kind of The efficient, green and continuous preparation process of sucralose has extremely high application value and practicability.

In the description of this application, it should be noted that the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer" etc. The indicated orientation or positional relationship is based on the orientation or positional relationship shown in the drawings, and is only for the convenience of describing the present application and simplifying the description, rather than indicating or implying that the referred device or element must have a specific orientation, use a specific orientation construction and operation, therefore should not be construed as limiting the application. In addition, the terms "first", "second", "third", etc. are used for descriptive purposes only and should not be construed as indicating or implying relative importance.

In the description of this application, it should be noted that unless otherwise specified and limited, the terms "installation", "connection", and "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 can be mechanically connected or electrically connected; it can be directly connected or indirectly connected through an intermediary, and it can 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.

To sum up, the above is only a specific implementation manner of the present application. Under the above teaching of the present application, those skilled in the art can make other improvements or modifications on the basis of the above embodiments. Those skilled in the art should understand that the above specific description is only to better explain the purpose of the present application, and the protection scope of the present application should be based on the protection scope of the claims.

In addition, those skilled in the art will appreciate that although some embodiments described herein include some features included in other embodiments but not others, combinations of features from different embodiments are meant to be within the scope of the present application. and form different embodiments. For example, in the following claims, any of the claimed embodiments may be used in any combination.

Claims (14)

1. A preparation method of sucralose, characterized in that, comprising:

   Neutralization step: make the chlorination reaction liquid, the first liquid caustic soda and the first reused water for preparing sucralose-6-ester enter the neutralization reaction rectification tower in sections, and carry out the neutralization reaction under evaporation conditions, from the The solvent mixture is extracted from the tower top of the neutralization reaction rectification; the chlorination reaction neutralization liquid is extracted from the bottom of the neutralization reaction rectification tower;

   Hydrolysis step: make the chlorination reaction neutralization liquid, the second liquid alkali and the second reused water enter the hydrolysis reaction rectification tower in stages, and carry out the alkaline hydrolysis reaction under the evaporation condition, from the hydrolysis reaction rectification tower The waste aqueous solution is extracted from the top of the tower, and the sucralose aqueous solution is extracted from the bottom of the hydrolysis reaction distillation tower;

   Extraction and purification step: after adjusting the sucralose aqueous solution to neutrality, sequentially perform extraction, oxidation and back extraction for purification; and

   Crystallization step: Concentrate, crystallize and filter the purified sucralose aqueous solution to obtain crude sucralose product and crystallization mother liquor.
2. The method according to claim 1, further comprising:

   Mother liquor circulation recovery step: the crystallization mother liquor is recycled into the sucralose aqueous solution that will enter the crystallization step, and the recovery times are 1 to 5 times.
3. The method according to claim 1, characterized in that, the tower height of the neutralization reactive distillation tower is 10-30m;

   The feeding position of the chlorination reaction liquid is at a position of 3/10 to 2/5 of the tower height from the top of the tower, and the feeding position of the first liquid caustic soda is at a position of 1/2 to 3 of the tower height from the tower top. /5 position, the feed position of the first recycled water is at a position of 7/10 to 4/5 of the tower height from the top of the tower.
4. The method according to claim 1, characterized in that, in the neutralization step, when the neutralization reaction is carried out, the temperature at the top of the neutralization reaction distillation tower is set to 30-40° C. The temperature is set at 50-60°C.
5. The method according to claim 1, characterized in that, in the hydrolysis step, the tower height of the hydrolysis reaction distillation tower is 10-30m;

   The feed position of the chlorinated liquid neutralizing liquid is 2/5 to 3/7 of the tower height from the top of the tower, and the feed position of the second liquid caustic soda is 1/2 of the tower height from the tower top. ~3/5 of the position, the feed position of the second recycled water is at a position of 4/5~9/10 of the tower height from the top of the tower.
6. The method according to claim 1, characterized in that, in the hydrolysis step, when carrying out the hydrolysis reaction, the temperature at the top of the neutralization reaction distillation tower is set at 30 to 40°C, and the temperature at the bottom of the column is set at It is 50-60°C.
7. The method according to claim 1, characterized in that, both the neutralization reaction rectification tower and the hydrolysis reaction rectification tower are packed towers or tray towers, preferably packed towers, wherein, in the packed towers The filler is polytetrafluoro corrugated plate or θ ring, and the height of the filler is 1/3 to 2/3 of the height of the packed tower.
8. The method according to claim 1, characterized in that, in the neutralization step, the volume ratio of the chlorination reaction solution, the first liquid alkali and the first recycled water is 10-15:1:1 ;

   In the hydrolysis step, the volume ratio of the chlorination reaction neutralization liquid, the second liquid caustic soda and the second recycled water is 40-60:1:10-20.
9. The method according to claim 1, characterized in that, both the first liquid caustic and the second liquid caustic are aqueous solutions of sodium hydroxide or potassium hydroxide, preferably aqueous solutions of sodium hydroxide.
10. The method according to claim 1, characterized in that, in the extraction and purification step, adjusting the sucralose aqueous solution to neutrality comprises:

    The pH value of the sucralose aqueous solution is adjusted to 6-8 by using an inorganic acid, wherein the inorganic acid is one of hydrochloric acid, sulfuric acid or phosphoric acid.
11. The method according to claim 1, characterized in that, in the extraction and purification step, the extractant used for extraction is ethyl acetate and/or butyl acetate;

    The ratio of the volumetric dosage of the extractant to the chlorination reaction neutralizing liquid is 1-5:1.
12. The method according to claim 1, characterized in that, in the extraction and purification step, the oxidant used in the oxidation is sodium hypochlorite or ozone; wherein, the mass consumption of the sodium hypochlorite is the volume of the organic phase obtained by the extraction 0.01% to 0.1% of the ozone; the volumetric dosage of the ozone is 0.01% to 0.1% of the volume of the organic phase obtained by the extraction;

    The oxidation time of the oxidation is 3-12 hours.
13. method according to claim 1, is characterized in that, in described extracting and purifying step, the stripping agent of described stripping is water, and the volume consumption of described stripping agent and the volume of the organic phase that described extraction obtains The ratio is 1 to 5:1.
14. The method according to claim 1, characterized in that, in the crystallization step, the concentration temperature of the concentration is 40-60°C, the concentration vacuum is -0.1--0.5Mpa, and the sucralose is concentrated to The concentration of sucralose in the aqueous solution is 80-140g/L.

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