Continuous reactive distillation method based on azeotropic system

Abstract

The invention provides a method for preparing sucralose through continuous reactive distillation based on an azeotropic system, which comprises the following steps: forming an alcohol-water-acetate ternary azeotropic system, and synchronously fractionating acetate and water out of the reaction system in the reactive distillation process, thereby achieving the purpose of dehydration. According to the invention, an azeotropic system is combined for reactive distillation for the first time, and a series of subsequent problems caused by moisture carried by the sucralose-6-acetate crude product which puzzles the industry for a long time are solved.

Description

Technical Field

[0001] The invention belongs to the field of sucralose preparation, and specifically discloses a method for preparing sucralose through continuous reaction distillation based on an azeotropic system. Background Art

[0002] Sucralose, molecular formula is C 12 H 19 O 8 Cl 3 Sucralose is a white powder product that is easily soluble in water and 600 times sweeter than sucrose. It has the characteristics of high sweetness, strong sweetness, no toxicity, no side effects, almost no absorption in the human body, almost zero caloric value, good physical and chemical properties and a wide range of applications.

[0003] At present, there are many reports on methods for preparing sucralose using sucralose-6-acetate as raw material, mainly including organic amine catalysis method (for example, Chinese patents CN101260127A, CN112771060A and CN101260127A), ion exchange resin catalysis method (for example, Chinese patents CN112409419A and CN102336787A) and base catalysis method (for example, Chinese patent CN113004345A). Among them, the base catalysis method is simple to operate, has low production cost, and is the most widely used.

[0004] The traditional base catalysis method generally uses recrystallized and dried sucralose-6-acetate as the raw material for alcoholysis reaction, and a strong base (sodium methoxide, sodium hydroxide) as a catalyst to remove the acetylation group in methanol solution to generate sucralose and methyl acetate as a byproduct. Intermittent operation is common in industry. The traditional base catalysis system has the advantages of mild conditions and rapid reaction, but it also has certain disadvantages, such as low yield, the presence of various byproducts such as sodium acetate, sodium chloride, sucralose, monochlorosucrose, etc., and a large amount of catalyst: the alcoholysis reaction is a reversible process. Methanol needs to be added many times during the reaction, and the methyl acetate generated by the reaction is vaporized and removed to promote the forward reaction. The reaction time is long, the solvent consumption is large, and the operation is cumbersome; in addition, vaporization cannot completely remove the methyl acetate generated by the reaction, resulting in insufficient conversion rate, large sucralose-6-acetate residue, and high difficulty in subsequent separation. Patent CN113004345A proposes a continuous reactive distillation method for preparing sucralose, which uses a reactive distillation tower for alcoholysis reaction. Methyl acetate generated during the reaction is continuously distilled and separated from the reaction zone, which can break the kinetic equilibrium of the transesterification reaction and promote the transesterification reaction, thereby improving the single-pass conversion rate of sucralose-6-ester and solving the problem of high energy consumption caused by multiple evaporation of methyl acetate.

[0005] Patent CN113004345A also proposed the problem of water enrichment in the bottom of the tower in the continuous reactive distillation method. Excessive water content will cause the hydrolysis of sucralose-6-acetate in the alcoholysis process to generate acetic acid and hydrogen chloride, and further react with sodium methoxide (sodium hydroxide) to generate sodium acetate and sodium chloride, so that the catalyst (alcohol base) is consumed, and the catalyst needs to be supplemented, so the amount of catalyst is increased; at the same time, excessive water content will also cause sucralose to hydrolyze to generate dichlorosucrose and monochlorosucrose, thereby reducing the yield of sucralose. The patent also pointed out that the enrichment of water in the bottom of the tower is caused by the failure of sucralose-6-ester to be dehydrated. Patent CN112574258A further proposed that the water contained in the deacetylation reaction system of sucralose-6-ethyl ester leads to the formation of sodium acetate, which in turn makes the product have an acetic acid smell. It can be seen that the negative impact of the water contained in sucralose-6-acetate on the process of alcoholysis reaction to generate sucralose has become a problem that must be solved in sucralose production. At present, the technical means to solve this problem in the industry include drying the sucralose-6-ethyl ester raw material as described in CN112574258A, using molecular sieves to remove the sucralose-6-ethyl ester solution to make the water content in the solution reach the specified value, or increasing the amount of anhydrous methanol used to make the water content in the solution reach the specified value, etc. The most common one is drying. In addition, patent CN112574258A further proposes that since sucralose-6-acetate forms a eutectic with water, conventional drying cannot remove the crystal water. The dried sucralose-6-acetate still has 7-8% of crystal water, so that there will be a certain hydrolysis phenomenon during the alcoholysis process. To solve this problem, patent CN112574258A proposes to perform azeotropic dehydration on sucralose-6-acetate to obtain dehydrated sucralose-6-acetate with a water content of 100~8000ppm as a reaction raw material for preparing sucralose by alcoholysis. Summary of the invention

[0006] The present invention is mainly based on the further improvement proposed in patent CN113004345A, and the main purpose is to propose a new method for solving the problem of water content in sucralose-6-acetate raw materials.

[0007] To achieve the above object, the present invention adopts the following technical solution: The present invention provides a method for continuous reactive distillation based on an azeotropic system, which can prepare sucralose from sucralose-6-acetate, comprising the following steps: S1, mixing and dissolving crude sucralose-6-acetate with alcohol to obtain a reaction raw material; S2, sending the reaction raw materials and the catalyst solution into a distillation tower for reactive distillation.

[0008] S3, taking out the materials from the bottom of the tower and obtaining the product sucralose through post-processing.

[0009] The specific process of mixing and dissolving the crude sucralose-6-acetate and alcohol in S1 is as follows: after mixing, the temperature is raised to 40-80° C. for dissolution to obtain a reaction raw material.

[0010] Among them, the water content of crude sucralose-6-acetate in S1 is more than 7%.

[0011] Among them, the property that the alcohol described in S1 needs to have is that it can form an alcohol-water-acetate ternary azeotropic system with water and the reaction product ester. After the azeotropic system is formed, the acetate and water can be synchronously distilled out of the reaction system in the reaction distillation process, thereby achieving the purpose of dehydration. The optional alcohol is typically ethanol, which can form an ethanol-water-ethyl acetate ternary azeotropic system in the reaction system, which is a common ternary azeotropic system in the chemical process. Further, in the reaction distillation process of S2, the ethanol-water-ethyl acetate azeotrope can be separated from the reaction system by continuous fractionation from the top of the tower, and water is taken out while the product ethyl acetate is separated, solving the problem of water enrichment in the bottom of the tower. Other optional alcohols such as n-propanol, isopropanol, propylene glycol, butanol, etc. The selection of alcohol in the alcoholysis reaction is one of the main improvements of this scheme compared with CN113004345A and other prior arts. In the conventional scheme, the alcoholysis reaction is generally carried out in an alkaline system environment formed by a methanol solution of sodium methoxide to remove the acetyl group, but methanol cannot form the aforementioned azeotropic system, so the alcohol used in this scheme does not include methanol. The present invention proposes for the first time to carry out reactive distillation in combination with an azeotropic system, thereby solving a series of subsequent problems caused by the crude sucralose-6-acetate product carrying moisture, which has long troubled the industry.

[0012] Among them, the mass ratio of crude sucralose-6-acetate to alcohol in S1 is 1:1~1:5.

[0013] Wherein, the catalyst solution described in S2 is an alcohol solution of alkali metal alkoxide or alkali metal hydroxide, and the preparation step is specifically to obtain the catalyst solution by dissolving and mixing the alkali metal alkoxide or alkali metal hydroxide with alcohol.

[0014] Wherein, the mass ratio of alcohol to alkali metal alkoxide / alkali metal hydroxide is 5:1-10:1.

[0015] Among them, the feed mass ratio of S2 reaction raw materials to catalyst is 80:1-300:1.

[0016] Among them, the temperature range of S2 reactive distillation is 25-70℃.

[0017] Among them, the residence time of materials in the S2 reaction distillation process is 0.1-1h.

[0018] Before the reaction raw materials and catalyst solution in S2 are sent to the distillation tower, they are first sent to the pre-reactor for pre-reaction, and the reaction liquid after the pre-reaction is sent to the distillation tower for further reaction. The purpose of the pre-reaction is mainly to speed up the efficiency of the overall reaction. The reactants can quickly start to react in the pre-reactor and initially establish a reaction equilibrium state. Compared with directly entering the distillation tower for reaction, the initial reaction efficiency can be improved.

[0019] Wherein, the pre-reactor is a reactor, a tubular reactor or a fixed bed reactor.

[0020] The reaction temperature in the pre-reactor is in the range of 25-50°C.

[0021] The reaction time in the pre-reactor is 0.5-2h.

[0022] Furthermore, the post-treatment described in S3 includes neutralization, crystallization, filtration, drying, etc., to remove a small amount of alkali and water remaining in the kettle liquid. Specifically, alkali neutralization can be performed by using a resin to adsorb alkali metal ions.

[0023] Another aspect of the present invention provides a continuous reactive distillation system based on an azeotropic system, which comprises a raw material tank and an azeotropic reactive distillation device, wherein the reaction raw materials in the raw material tank comprise crude sucralose-6-acetate with a water content of more than 7% and alcohol.

[0024] The device further comprises a pre-reactor arranged before the azeotropic reaction distillation device. The pre-reactor can be a reactor, a tubular reactor or a fixed bed reactor. Preferably, the pre-reactor is a tubular reactor or a fixed bed reactor, which can realize continuous reaction. Preferably, the catalyst is loaded in the fixed bed reactor.

[0025] The advantages of the present invention are: 1. By using higher alcohols for the reaction, the traditional drying process of crude sucralose-6-acetate is avoided. Higher alcohols and water form a ternary azeotropic system, so that water can be continuously taken out of the system during the reaction; 2. For the first time, the azeotropic reaction distillation technology was applied to the process of preparing sucralose by alcoholysis, solving a series of problems caused by water in the system; 3. In the preferred embodiment, a tubular reactor or a fixed bed reactor can be coupled with an azeotropic reaction distillation device to achieve overall continuous synthesis; the catalyst can also be loaded on a fixed bed reactor to further simplify the overall process. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 A flow chart of preparing sucralose according to Example 1; Figure 2 This is a flow chart of preparing sucralose in Comparative Example 1. DETAILED DESCRIPTION

[0027] In order to make the above features and advantages of the present invention more clearly understood, the following embodiments are given for detailed description. The methods of the present invention are all conventional methods in the art unless otherwise specified.

[0028] The method for detecting the water content in each embodiment is to dissolve the test object with a solvent and then use a moisture analyzer to detect the water content.

[0029] like Figure 1 As shown. The crude product of sucralose-6-acetate (TGS-6a) obtained in the previous process is recrystallized. The crude TGS-6a is dissolved in water, and the refined TGS-6a is obtained after recrystallization and filter pressing, and the mother liquor is recycled. According to the test, the general range of water content in the refined TGS-6a is 7-15wt%.

[0030] 500 g of sucralose-6-acetate (containing 10 wt% water) was mixed with 800 g of anhydrous ethanol, and the mixture was heated to 50° C. to dissolve, thereby obtaining a sucralose-6-acetate ethanol solution as a raw material for the reaction; 1.5 g of sodium hydroxide was mixed with 7.5 g of ethanol to dissolve, thereby obtaining a catalyst solution (sodium hydroxide ethanol solution); the sucralose-6-acetate ethanol solution and the sodium hydroxide ethanol solution were introduced into a pre-reaction kettle at a mass ratio of 300:1 for mixed pre-reaction, and the pre-reaction residence time was controlled to be 0.5 h, and the pre-reaction temperature was controlled to be 30° C. oC Subsequently, the reaction liquid enters the reaction distillation tower for reaction distillation. The distillation reaction temperature is 30 o C, the distillation pressure range is 5-20kPa, and the pressure is adjusted based on different azeotropic systems. The reasonable pressure range can be checked in the azeotropic manual. During the reaction, the top of the tower is continuously extracted, and the fraction is an ethanol-water-ethyl acetate ternary azeotrope. It can be seen that the distillation process effectively takes the product and water out of the reaction system. After the reaction, the kettle liquid is neutralized with resin to obtain crude sucralose; in the crude sucralose, sucralose-6-acetate is ≤50ppm, ethyl acetate is ≤50ppm, sucralose conversion rate is ≥99.9%, and yield is ≥99.9%.

[0031] Embodiment 1: This group of embodiments adopts Figure 1 The method shown is used to prepare sucralose. Alcohol and TGS-6a fine product are mixed at a mass ratio of 2:1 to prepare a reaction raw material sucralose-6-acetate ethanol solution. In the pre-reaction catalyst solution (prepared by mixing and dissolving 1.5g sodium hydroxide and 7.5g ethanol), the mass ratio of catalyst to TGS-6a is 0.1-0.2%. The pre-reaction temperature is 30 oC , the reaction residence time is 0.5h.

[0032] After the pre-reaction, the reaction liquid enters the distillation tower for continuous dehydration reaction distillation, and the distillate is taken out from the top of the tower for recovery. The composition range of the detected distillate is 10%-50% ethanol, 30-50% product ethyl acetate, and 5-10% water, which is an azeotropic composition.

[0033] After the reaction, the kettle liquid was neutralized to pH=7 by resin to obtain a crude sucralose product for post-treatment. According to the test, the residual TGS-6a in the crude sucralose product was ≤0.02% and the conversion rate was ≥99.98%.

[0034] Comparative Example 1: Figure 2 It is one of the processes in the prior art. The recrystallization process is consistent with the method of the present invention, except that, in order to avoid excessive water from being brought into the raw material, drying and dehydration are required after filter pressing, and the water content of the TGS-6a fine product finally obtained for entering the alcoholysis reaction is lower than that of the present invention, about 7-8wt%. The remaining water is crystallization water, which cannot be removed by simple drying, and thus still enters the reaction system.

[0035] Ethanol and TGS-6a fine product were mixed at a mass ratio of 2:1 to prepare the reaction raw material sucralose-6-acetate ethanol solution. Subsequently, it was mixed with the catalyst solution (prepared by mixing and dissolving 1.5g sodium hydroxide and 7.5g ethanol) and passed into the reactor for primary reaction. The mass ratio of the catalyst to TGS-6a was 0.34%. The reaction temperature was 30 oC , the reaction residence time is 2h. As the reaction proceeds, the ester content in the product gradually increases, and the reaction rate decreases. The ester in the reaction solution needs to be removed from the system to increase the conversion rate. Therefore, the reaction solution is concentrated in one stage to obtain fraction 1 for recycling. The temperature of the first stage concentration is 30 oC The primary concentration time is 1-2h, and the composition of fraction 1 is 90%-98% alcohol, the product acetate ≤10%, and water is about 1%. After the concentrate is supplemented with alcohol, the secondary reaction is continued. The alcohol and TGS-6a are mixed at a ratio of 2:1 (mass ratio) and the reaction temperature is 30 oC The reaction residence time is 2h. Then, secondary concentration is performed to obtain fraction 2 for recycling. The secondary concentration temperature is 30 oC , the concentration time is 1-2h. Fraction 2 consists of alcohol, acetate and water of about 1%. After neutralization of the concentrate, the crude sucralose product is obtained for post-treatment. According to the test, the residual TGS-6a in the crude sucralose product is 0.1-0.4%, and the conversion rate is 99.6-99.9%.

[0036] The following are specific examples of sucralose deesterification based on different azeotropic systems: Embodiment 2: This embodiment uses ethanol for alcoholysis, and the specific implementation process is: The alcoholysis raw material and the catalyst solution are sent to a pre-reactor for reaction, and the materials after the reaction are sent to a reactive distillation tower for reaction, wherein the pre-reactor temperature is 35°C, the reaction time is 30min, the filling height of the distillation tower is 8m (the height of the reaction section is 6m, the height of the distillation section is 2m), the top temperature of the reactive distillation tower is 25°C, and the temperature of the tower bottom is 35°C; the feed mass ratio of the materials is alcoholysis raw material: catalyst solution = 300:1; wherein the alcoholysis raw material is sucralose-6-acetate (containing 8wt% water) and ethanol mixed at a mass ratio of 1:2, and then heated to 50°C for dissolution; the catalyst solution is sodium hydroxide and ethanol mixed and dissolved at a mass ratio of 1:5; The bottom liquid of the reactive distillation tower is treated with resin neutralization to obtain crude sucralose, in which sucralose-6-acetate is ≤50ppm, ethyl acetate is ≤50ppm, sucralose conversion rate is >99.9%, and yield is ≥99.8%; the fraction is a mixture of ethyl acetate, water, and ethanol, in which ethyl acetate is 65%, water is 8%, and ethanol is 27%.

[0037] Embodiment 3: This embodiment uses n-propanol for alcoholysis, and the specific implementation process is: The alcoholysis raw material and the catalyst solution are sent to a pre-reactor for reaction, and the materials after the reaction are sent to a reactive distillation tower for reaction, wherein the pre-reactor temperature is 35°C, the reaction time is 45min, the filling height of the distillation tower is 8m (the reaction section height is 6m, the distillation section height is 2m), the top temperature of the reactive distillation tower is 27°C, and the tower bottom temperature is 36°C; the feed mass ratio of the materials is alcoholysis raw material: catalyst solution = 300:1; wherein the alcoholysis raw material is sucralose-6-acetate (containing 13wt% water) and n-propanol mixed at a mass ratio of 1:1.8, and then heated to 50°C for dissolution; the catalyst solution is sodium hydroxide and n-propanol mixed and dissolved at a mass ratio of 1:7; The bottom liquid of the reactive distillation tower is neutralized with resin to obtain crude sucralose, wherein the crude sucralose-6-acetate is ≤50ppm, the n-propyl acetate is ≤50ppm, the sucralose conversion rate is >99.9%, and the yield is ≥99.4%; the fraction is a mixed liquid of n-propyl acetate, water, and n-propanol, wherein n-propyl acetate is 70%, water is 15%, and n-propanol is 15%.

[0038] Embodiment 4: This embodiment uses n-butanol for alcoholysis, and the specific implementation process is: The alcoholysis raw material and the catalyst solution are sent to a pre-reactor for reaction, and the materials after the reaction are sent to a reactive distillation tower for reaction, wherein the pre-reactor temperature is 35°C, the reaction time is 1h, the filling height of the distillation tower is 8m (the reaction section height is 6m, the distillation section height is 2m), the top temperature of the reactive distillation tower is 25°C, and the tower bottom temperature is 35°C; the feed mass ratio of the materials is alcoholysis raw material: catalyst solution = 300:1; wherein the alcoholysis raw material is sucralose-6-acetate (containing 13wt% water) and n-butanol mixed at a mass ratio of 1:1.8, and then heated to 50°C for dissolution; the catalyst solution is sodium hydroxide and n-butanol mixed and dissolved at a mass ratio of 1:8; The bottom liquid of the reactive distillation tower is neutralized with resin to obtain crude sucralose, wherein the crude sucralose-6-acetate is ≤50ppm, the n-butyl acetate is ≤50ppm, the sucralose conversion rate is >99.9%, and the yield is ≥99.6%; the fraction is a mixed liquid of n-butyl acetate, water, and n-butanol, wherein n-butyl acetate is 65%, water is 25%, and n-butanol is 10%.

[0039] Embodiment 5: This embodiment uses isopropanol for alcoholysis, and the specific implementation process is: The alcoholysis raw material and the catalyst solution are sent to a pre-reactor for reaction, and the materials after the reaction are sent to a reactive distillation tower for reaction, wherein the pre-reactor temperature is 35°C, the reaction time is 1h, the filling height of the distillation tower is 8m (the reaction section height is 6m, the distillation section height is 2m), the top temperature of the reactive distillation tower is 25°C, and the tower bottom temperature is 35°C; the feed mass ratio of the materials is alcoholysis raw material: catalyst solution = 300:1; wherein the alcoholysis raw material is sucralose-6-acetate (containing 10wt% water) mixed with isopropanol at a mass ratio of 1:1.8, and then heated to 50°C for dissolution; the catalyst solution is sodium hydroxide and isopropanol mixed and dissolved at a mass ratio of 1:7; The bottom liquid of the reactive distillation tower is neutralized with resin to obtain crude sucralose, wherein the crude sucralose-6-acetate is ≤50ppm, the isopropyl acetate is ≤50ppm, the sucralose conversion rate is >99.9%, and the yield is ≥99.9%; the fraction is a mixed liquid of isopropyl acetate, water and isopropyl alcohol, wherein isopropyl acetate is 62%, water is 13% and isopropyl alcohol is 25%.

[0040] It can be seen from the above embodiments and comparative examples that the beneficial effects of the present invention are: 1. The requirement for the water content in the raw material sucralose-6-acetate is not high, and the drying and dehydration step can be omitted; 2. Due to the reduction of water enrichment, catalyst deactivation is avoided to a large extent, thereby reducing the amount of catalyst used; 3. By adopting the distillation method, the proportion of ester in the gas phase is much higher than that of direct vaporization, and the alcohol required for the reaction is also greatly reduced, thereby reducing the consumption of solvents; 4. The process is streamlined, the deesterification effect is good, and the reaction time is greatly reduced.

[0041] In summary, the present invention adopts reactive distillation to carry out alcoholysis reaction, realizes continuous production, and improves reaction efficiency. Figure 2 8h shortened to Figure 1 2h, greatly shortening the reaction time. Furthermore, the present invention combines azeotropic distillation with reactive distillation, utilizes the reaction product, alcohol and water to form a multi-element azeotrope, removes water in the system while continuously removing the ester generated by the reaction, thereby destroying the reaction balance and reducing the moisture content of the reaction system, greatly improving the conversion rate and yield of the reaction, and avoiding the occurrence of hydrolysis caused by the enrichment of water in the bottom of the tower.

[0042] The above description is only a preferred embodiment of the present invention. All equivalent changes and modifications made according to the scope of the patent application of the present invention should fall within the scope of the present invention.

Claims

1. A method for preparing sucralose by continuous reactive distillation based on an azeotropic system, characterized in that: The following steps are involved: S1, mixing and dissolving crude sucralose-6-acetate with alcohol to obtain a reaction raw material; S2, sending the reaction raw materials and the catalyst solution into a distillation tower for reactive distillation; S3, taking out the materials from the bottom of the tower and obtaining the product sucralose through post-processing.

2. The method according to claim 1, characterized in that: The alcohol can form an alcohol-water-acetate ternary azeotropic system, and the acetate is an ester generated by the reaction of the alcohol and sucralose-6-acetate.

3. The method according to claim 2, characterized in that The alcohol in step S1 includes one of ethanol, n-propanol, isopropanol, propylene glycol and butanol.

4. The method according to claim 1, characterized in that: The specific process of mixing and dissolving the crude sucralose-6-acetate and alcohol in S1 is as follows: after mixing, the temperature is raised to 40-80° C. for dissolution to obtain a reaction raw material.

5. The method according to claim 1, characterized in that The water content of the crude sucralose-6-acetate in S1 is above 7 wt %.

6. The method according to claim 1, characterized in that The mass ratio of the crude sucralose-6-acetate to the alcohol is 1:1 to 1:

5.

7. The method according to claim 1, characterized in that S2 The catalyst solution is an alcohol solution of an alkali metal alkoxide or an alkali metal hydroxide, and the specific preparation step is to dissolve and mix the alkali metal alkoxide or the alkali metal hydroxide with alcohol to obtain the catalyst solution.

8. The method according to claim 1, characterized in that The feed mass ratio of S2 reaction raw materials to catalyst solution is 80:1-300:1, the temperature range of S2 reaction distillation is 25-70°C; the residence time of materials in the reaction distillation process is 0.1-1h.

9. The method according to claim 1, characterized in that: Before the reaction raw materials and catalyst solution in S2 are sent to the distillation tower, they are first sent to the pre-reactor for pre-reaction, and the reaction liquid after the pre-reaction is sent to the distillation tower for further reaction; wherein the pre-reactor is a reactor, a tubular reactor or a fixed bed reactor; the reaction temperature range in the pre-reactor is 25-50°C; the reaction time in the pre-reactor is 0.5-2h.

10. The method according to claim 1, characterized in that The post-treatment described in S3 includes neutralization, crystallization, filtration and drying.

Images