WO2022246862A1 - 乙酰磺胺酸钾组合物 - Google Patents

乙酰磺胺酸钾组合物 Download PDF

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WO2022246862A1
WO2022246862A1 PCT/CN2021/097010 CN2021097010W WO2022246862A1 WO 2022246862 A1 WO2022246862 A1 WO 2022246862A1 CN 2021097010 W CN2021097010 W CN 2021097010W WO 2022246862 A1 WO2022246862 A1 WO 2022246862A1
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Prior art keywords
acesulfame potassium
reaction
solution
catalyst
potassium
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PCT/CN2021/097010
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English (en)
French (fr)
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周睿
丁震
陈永旭
杨峰宝
刘刚
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安徽金禾实业股份有限公司
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Priority to PCT/CN2021/097010 priority Critical patent/WO2022246862A1/zh
Priority to CN202180001418.2A priority patent/CN113454073A/zh
Publication of WO2022246862A1 publication Critical patent/WO2022246862A1/zh

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D291/00—Heterocyclic compounds containing rings having nitrogen, oxygen and sulfur atoms as the only ring hetero atoms
    • C07D291/02—Heterocyclic compounds containing rings having nitrogen, oxygen and sulfur atoms as the only ring hetero atoms not condensed with other rings
    • C07D291/06—Six-membered rings

Definitions

  • the invention belongs to the technical field of fine chemical manufacturing, and in particular relates to an acesulfame potassium composition.
  • Acesulfame potassium also known as AK sugar
  • AK sugar is a widely used sugar substitute food additive. Its appearance is white crystalline powder.
  • As an organic synthetic salt its taste is similar to sugarcane, and it is easily soluble in water. , Slightly soluble in alcohol, its chemical properties are stable, and it is not easy to break down and fail; it does not participate in the body's metabolism and does not provide energy; it has high sweetness and low price; it has no cariogenicity; it has good stability to heat and acid.
  • the diketene-sulfur trioxide method is widely used.
  • the specific reaction steps include: reacting sulfamic acid with amine to form amine sulfamic acid salt, and then reacting amine sulfamic acid with diketene , forming acetylacetamide salt; in the presence of sulfur trioxide, acetylacetamide salt undergoes a cyclization reaction to form a cyclic sulfur trioxide adduct; the cyclic compound is hydrolyzed to obtain the hydrolyzate (ASH); subsequent oxidation with hydrogen Potassium treatment of the hydrolyzate yields acesulfame potassium (ASK).
  • the final commercial acesulfame potassium finished product was a mixture of acesulfame potassium and impurities, among which there were many kinds of components similar in structure to acesulfame potassium of organic impurities.
  • organic impurities the content of some organic substances is very similar to that of acesulfame potassium, such as the chloride of acesulfame potassium, and the content is extremely small, and it is difficult to remove it by general methods, but the impurities have a darker color, resulting in acesulfame potassium chloride.
  • the finished product of potassium acesulfame potassium is light brown, which affects the quality of acesulfame potassium.
  • the present application is proposed in order to provide an acesulfame potassium composition that overcomes the above problems or at least partially solves the above problems.
  • an acesulfame potassium composition comprises acesulfame potassium and acesulfame potassium chloride, and the acesulfame potassium composition is prepared by the following method, so that the chloride content of acesulfame potassium is less than 300ppm;
  • the method includes:
  • the step of sulfonation and cyclization dissolving sulfur trioxide in a solvent to form a cyclizing agent solution; causing the intermediate solution and the cyclizing agent solution to undergo a sulfonation and cyclization reaction under the action of a loaded solid base heterogeneous catalyst to obtain sulfonate Cyclization products;
  • Hydrolysis step the sulfonated cyclization product undergoes a hydrolysis reaction with a hydrolyzing agent to obtain a hydrolyzate solution;
  • Salt-forming step adding a salt-forming agent to the organic phase of the hydrolyzate solution to carry out a salt-forming reaction to obtain acesulfame potassium.
  • the content of chloride of acesulfame potassium is less than 100ppm.
  • the content of chloride of acesulfame potassium is less than 10 ppm.
  • the content of chloride of acesulfame potassium is less than 0.002-8ppm.
  • the solid acidic catalyst is a molecular sieve catalyst, a solid superacid catalyst or a solid heteropolyacid catalyst.
  • the molecular sieve catalyst is HZSM-5 molecular sieve and/or Na-ZSM-5 molecular sieve;
  • the solid superacid catalyst is SO 4 2- /Fe 2 O 3 type Catalyst;
  • the solid heteropolyacid catalyst is H 3 [PMo 12 O 14 ] ⁇ xH 2 O solid catalyst.
  • the supported solid base heterogeneous catalyst is a K 2 O/- ⁇ Al 2 O 3 catalyst, preferably, at K 2 O/- ⁇ Al 2 O 3 Silicone is added to the catalyst.
  • the reaction time of the sulfonation and cyclization reaction is 1-15s, preferably 1-3s.
  • the hydrolysis agent is an aqueous ethanol solution, wherein the mass fraction of ethanol in the aqueous ethanol solution is 60-85%.
  • the salt-forming agent is an ethanol solution of potassium ethoxide, wherein the mass fraction of potassium ethoxide is 10%-80%.
  • the beneficial effect of the present application is that, in the intermediate preparation process and the sulfonation ring closure process, the present application uses a specific solid-state catalyst to carry out the catalytic reaction, and prepares an acesulfame potassium composition with very little impurity content; on the one hand, in During the preparation of intermediates, solid acidic catalysts are used instead of traditional acetic acid, which greatly shortens the acylation reaction time, improves the reaction yield of intermediate products, reduces the organic impurities in the products, and further reduces the the production cost of honey; on the other hand, in the sulfonation ring-closure reaction step, a loaded solid base heterogeneous catalyst is used for catalysis, and the catalyst can promote the forward progress of the sulfonation ring-closure step and improve the yield of the sulfonation ring-closure product , further, improve the yield of final product acesulfame potassium; also can reduce the content of impurity in the product simultaneously.
  • the present application can produce the acesulfame potassium composition with very little impurity content through the combined use of the two catalysts, wherein the content of the chloride of acesulfame potassium as the impurity can reach below 300ppm, greatly reducing the The post-treatment process of acesulfame potassium is improved, and the production cost of acesulfame potassium is reduced.
  • the idea of this application is that the crude product of acesulfame has low purity and excessive content of organic impurities, which leads to a darker color of the product and affects the user experience; subsequent complex and costly post-treatment processes are required to achieve an ideal purification effect
  • the present application provides an acesulfame potassium composition, which is prepared by a specific method, and the content of the impurity acesulfame potassium chloride can reach below 300ppm.
  • the acesulfame potassium composition provided by the application comprises the chloride of acesulfame potassium and acesulfame potassium, and in the composition, the content of the chloride of acesulfame potassium is less than 300ppm, and the content of the acesulfame potassium composition
  • the preparation method at least includes the following steps S110 to S140:
  • Intermediate preparation step S110 adding triethylamine to the sulfamic acid solution for amination reaction to generate a sulfamic acid ammonium salt solution; adding diketene to the obtained sulfamic acid ammonium salt solution, and under the action of a solid acidic catalyst, An acylation reaction was carried out to obtain an intermediate solution.
  • the preparation of the intermediate is more carefully divided into two small steps. First, it is the preparation of ammonium sulfamate, and then the intermediate is prepared by reacting ammonium sulfamate with diketene, that is, acetoacetamide-N-sulfonic acid triethyl amine salt.
  • the ammonium salt of sulfamic acid is obtained by adding triethylamine to the sulfamic acid solution for amination reaction.
  • sulfamic acid is dissolved in the first solvent to configure the first reaction solution
  • triethylamine is dissolved in the second solvent to configure the second reaction solution
  • the second The reaction solution is added to the first reaction solution to carry out amination reaction to form a sulfamic acid ammonium salt solution.
  • the first solvent and the second solvent are inert organic solvents that can provide a reaction environment for the amination reaction, such as dichloromethane.
  • Sulfamic acid and triethylamine react exothermicly. During the reaction, the heat generated will vaporize part of the dichloromethane, and the vaporized dichloromethane will leave the reaction system to take away the heat produced. Further, the vaporized dichloromethane Methane can also be recycled.
  • a kind of specific implementation of generating sulfamic acid ammonium salt solution is given below, and this embodiment is only used as an illustration, and the specific production process of sulfamic acid ammonium salt solution can adopt any one in the prior art.
  • the second reaction liquid is added dropwise into the first reaction liquid.
  • the pH value is 7-9, and the reaction is left to stand for 1 hour.
  • the above-mentioned reacted material is ammonium sulfamate solution.
  • ammonium sulfamate solution After the ammonium sulfamate solution is obtained, the ammonium sulfamate solution is reacted with diketene to obtain acetoacetamide-N-sulfonic acid triethylamine salt as an intermediate for preparing acesulfame potassium.
  • the solid acidic catalyst can provide enough acidic sites for the acylation reaction. On the one hand, it can effectively catalyze the smooth progress of the acylation reaction of ammonium sulfamate and diketene. On the other hand, the solid acidic catalyst will not be mixed into the reaction product. No special treatment process is required in the follow-up, which saves post-treatment economy and time costs; and avoids the adverse effects on the product phase of the final product caused by the acetic acid impurities that are not removed in the prior art.
  • diketene is dissolved in a third solvent to prepare a third reaction solution.
  • the third solvent is an inert organic solvent that can provide a reaction environment for the amination reaction, such as dichloromethane.
  • Fill the reactor with a solid acidic catalyst add the ammonium sulfamate solution and the third reaction solution to the reactor in sequence, and react under preset conditions to form acetoacetamide-N-sulfonic acid triethylamine salt solution as an intermediate solution.
  • a continuous reactor can be selected to realize the present application, such as a fixed bed reactor, a continuous stirred tank reactor or a microchannel reactor, etc.
  • the fixed bed reactor is taken as an example to briefly explain the reaction process.
  • the reaction can be ended after the preset reaction time is reached, and the product acetoacetamide-N-sulfonic acid triethylamine salt solution is obtained. Due to the characteristics of the fixed bed reactor, the reaction can be carried out continuously and is suitable for large-scale industrial production.
  • Sulfonation and cyclization step S120 dissolving sulfur trioxide in a solvent to form a cyclizing agent solution; allowing the intermediate solution and the cyclizing agent solution to undergo a sulfonation and cyclization reaction under the action of a loaded solid base heterogeneous catalyst to obtain Sulfonated cyclization products.
  • the acetylacetamide salt is usually directly reacted with sulfur trioxide, and such reaction efficiency is not high, and some impurities similar in structure to acesulfame potassium are also caused Remains in the final product acesulfame potassium, and the reaction yield cannot reach a satisfactory level.
  • the sulfonation ring closure step in the present application is completed under the action of a supported solid base heterogeneous catalyst.
  • the catalyst can promote the forward progress of the sulfonation and cyclization step, increase the yield of the sulfonation and cyclization product, and further increase the yield of the final product acesulfame potassium; meanwhile, it can also reduce the content of impurities in the product.
  • Hydrolysis step S130 the sulfonated cyclization product undergoes a hydrolysis reaction with a hydrolysis agent to obtain a hydrolyzate solution.
  • the sulfonated cyclization product undergoes a hydrolysis reaction with a hydrolysis agent, and the cyclization product is hydrolyzed into the precursor ASH of acesulfame potassium, which is different from the traditional process of using an acidic solution for hydrolysis reaction.
  • This application uses a hydrolysis agent, which can shorten the hydrolysis process. Time, along with the reduction of hydrolysis time is the reduction of the impurity content that may be produced by hydrolysis.
  • the hydrolyzing agent is water or ethanol aqueous solution, which significantly reduces the content of impurities in the cyclization product ASH, reduces the difficulty of subsequent purification of acesulfame potassium, and reduces the cost of purification of acesulfame potassium.
  • a flow reactor is adopted in the present application, so that the preparation of acesulfame K is continuous, which is suitable for large-scale process production.
  • a salt-forming step S140 adding a salt-forming agent to the organic phase of the hydrolyzate solution to carry out a salt-forming reaction to obtain acesulfame potassium.
  • potassium hydroxide or an aqueous potassium hydroxide solution is usually used to perform a salt-forming reaction with the hydrolyzed product, thereby obtaining acesulfame potassium (ASK).
  • ASK acesulfame potassium
  • salt-forming reaction refers to the process in which the cation of potassium hydroxide is exchanged with the anion of the hydrolyzate to generate the potassium salt of acesulfame.
  • a salt-forming agent can be used instead of traditional potassium hydroxide or potassium hydroxide aqueous solution to carry out a salt-forming reaction
  • inorganic impurities include but are not limited to potassium fluoride, potassium sulfate, etc.
  • the salt-forming agent includes, but is not limited to, an ethanol solution of potassium hydroxide or an ethanol solution of potassium ethoxide.
  • the content of the chloride of acesulfame potassium can reach below 300ppm; in some embodiments, the content of the chloride of acesulfame potassium can reach below 100ppm; in another In some embodiments, the content of acesulfame potassium chloride can reach below 10 ppm; in still other embodiments, the content of acesulfame potassium chloride can reach 0.002-8 ppm.
  • a specific solid catalyst is used for the catalytic reaction, and an acesulfame potassium composition with very little impurity content is prepared; on the one hand, in the intermediate
  • a solid acidic catalyst is used instead of traditional acetic acid, which greatly shortens the acylation reaction time, improves the reaction yield of intermediate products, reduces the organic impurities in the product, and further reduces the acesulfame potassium.
  • the catalyst in the sulfonation cyclization reaction step, adopt load-type solid base heterogeneous catalyst to catalyze, the catalyst can impel the forward progress of sulfonation cyclization step, improve the yield of sulfonation cyclization product, further Ground, improve the yield of final product acesulfame potassium; Also can reduce the content of impurity in the product simultaneously.
  • the present application can produce the acesulfame potassium composition with very little impurity content through the combined use of the two catalysts, wherein the content of the chloride of acesulfame potassium as the impurity can reach below 300ppm, greatly reducing the The post-treatment process of acesulfame potassium is improved, and the production cost of acesulfame potassium is reduced.
  • a solid acidic catalyst refers to a solid catalyst capable of providing acidic sites.
  • the solid acidic catalyst is a molecular sieve catalyst, a solid superacid catalyst or a solid heteropolyacid catalyst.
  • Molecular sieves have acid-base centers and can be used in acid-base catalyzed reactions.
  • the zeolite catalyst is used to replace the traditional acetic acid catalyst to provide acidic sites for the acylation reaction.
  • it can effectively catalyze the smooth progress of the acylation reaction between ammonium sulfamate and diketene.
  • the molecular sieve catalyst will not Mixed into the reaction product, no special treatment process is required in the follow-up, which saves post-treatment economy and time costs; and avoids the adverse effects on the product phase of the final product caused by the acetic acid impurities that are not removed in the prior art. .
  • a solid super acid is an acid whose acidity exceeds 100% sulfuric acid. If the acid strength is expressed by the Hammett acidity function H, the acid strength of 100% sulfuric acid is -11.93, and the acid whose acid strength is ⁇ -11.93 is a super acid.
  • Solid acidic catalysts are divided into two types, one type contains halogen, and fluorine sulfonic acid resin becomes fluoride immobilized compound; the other type does not contain halogen, which is composed of sulfate radicals adsorbed on the surface of metal oxides or hydroxides and burned at high temperature preparation.
  • the type of solid-state acidic catalyst is preferably the latter, that is, SO 4 2- /M x O y type superacid, wherein, M represents a metal atom, specifically Zn, Zr, Ti, Sn, etc.
  • M represents a metal atom, specifically Zn, Zr, Ti, Sn, etc.
  • SO 4 2- /Fe 2 O 3 type superacid catalyst is SO 4 2- /Fe 2 O 3 type superacid catalyst.
  • the application does not limit the type of heteropolyacid catalyst, any solid heteropolyacid catalyst that can provide acidic sites can be; in some embodiments of the application, the solid heteropolyacid catalyst is a solid heteropolyacid catalyst of Keggin type structure Acid catalysts, mainly Keggin-type structures of 1:12 series such as H 3 [PMO 12 O 14 ] ⁇ xH 2 O, which have strong acidity and oxidizing properties, and their acidity is usually higher than the content of each component of heteropolyacid
  • the acidity of oxyacid is strong, and it is very easy to oxidize other substances when used as an oxidant, so that it is in a reduced state and is very easy to regenerate.
  • the heteropolyacid catalyst can effectively catalyze the acylation reaction of ammonium sulfamate and diketene on the one hand.
  • due to its strong regenerative ability it significantly reduces the catalyst cost and further, reduces the production cost of acesulfame potassium.
  • the reaction time of the sulfonation ring closure step is not limited, and prior art may be referred to; in other embodiments of the present application, in the sulfonation ring closure step, the sulfonation ring closure reaction
  • the reaction time is 1-15s, preferably 1-3s.
  • a Venturi reactor can be introduced, so that the sulfonation ring closure reaction is carried out in the Venturi reactor, specifically, the acetoacetamide-N-sulfonic acid triethylamine salt solution is used as the working fluid , dissolve sulfur trioxide in the solvent to form a cyclizing agent solution as the injection fluid; the working fluid enters from the nozzle of the Venturi reactor, and the injection fluid enters from the suction chamber of the Venturi reactor to control the pressure of the working fluid The pressure is higher than the injection fluid; the working fluid and the injection fluid are mixed in the mixing section and the diffuser section of the Venturi reactor to carry out the sulfonation ring closure reaction, and the sulfonation ring closure product is sprayed into the flow reactor.
  • the pressure of the working fluid is 0.4-1.6MPa
  • the pressure of the injection fluid is 0.2-1.4MPa
  • the pressure of the working fluid is 0.2-0.4MPa higher than the pressure of the injection fluid.
  • the hydrolyzing agent is deionized water or an aqueous ethanol solution, preferably an aqueous ethanol solution, wherein the mass concentration of ethanol in the aqueous ethanol solution is preferably 60-85%.
  • the inventor used a hydrolysis agent, especially an aqueous solution of ethanol, and controlled the water content in the hydrolysis agent, which can significantly reduce the content of impurities in the acesulfame precursor ASH, and reduce the difficulty of subsequent acesulfame potassium purification. The cost of acesulfame purification is reduced.
  • the application is not limited, and the consumption of hydrolyzing agent can be determined according to the consumption of sulfur trioxide, specifically, in some embodiments of the application, the consumption of sulfur trioxide and the content of water in the hydrolyzing agent
  • the ratio of the amount of substances is 1:1-4, in some other embodiments, it is 1:1-1.5. That is to say, the amount of water in the hydrolyzing agent is preferably higher than that of sulfur trioxide.
  • the reaction temperature of the hydrolysis reaction is -40°C to 0°C, preferably -20°C to 0°C. That is to say, the hydrolysis reaction step of the present application is preferably carried out at a lower temperature.
  • any one of the prior art can be used for temperature control, such as air condensation technology, circulating water condensation technology and heat exchange plate Wait. After repeated tests, it was found that -40°C to 0°C is the most suitable temperature for the hydrolysis reaction.
  • reaction temperature is lower than -40°C, the hydrolysis may be incomplete, which will result in incomplete hydrolysis, and some cyclization products cannot be converted.
  • the conversion rate of raw materials is low; if the reaction temperature is higher than 0°C, the reaction temperature is too high, and the cyclization product is easy to decompose, which is not conducive to the development of the reaction towards the hydrolysis reaction.
  • the reaction time of the sulfonation cyclization reaction is within 1-15s, preferably controlled within 1-3s.
  • the hydrolysis agent is deionized water or an aqueous ethanol solution, preferably an aqueous ethanol solution, wherein the mass concentration of ethanol in the aqueous ethanol solution is preferably 30-65%.
  • the inventor used a hydrolysis agent, especially an aqueous solution of ethanol, and controlled the water content in the hydrolysis agent, which can significantly reduce the content of impurities in the acesulfame precursor ASH, and reduce the difficulty of subsequent acesulfame potassium purification. The cost of acesulfame purification is reduced.
  • the application is not limited, and the consumption of hydrolyzing agent can be determined according to the consumption of sulfur trioxide, specifically, in some embodiments of the application, the consumption of sulfur trioxide and the content of water in the hydrolyzing agent
  • the ratio of the amount of substances is 1:1-4, in some other embodiments, it is 1:1-1.5. That is to say, the amount of water in the hydrolyzing agent is preferably higher than that of sulfur trioxide.
  • the reaction temperature is set at 0 to 20°C
  • the medium temperature is 10 to 20°C
  • the reaction time is set to 3-10min. That is to say, the hydrolysis reaction step of the present application is preferably carried out at a lower temperature, because dichloromethane can take away a large amount of heat production, therefore, in the present application, temperature control is easier to achieve, using the prior art Any one can be used, such as air condensation technology, circulating water condensation technology and heat exchange plate, etc.
  • the reaction time of the hydrolysis reaction step can be significantly shortened, and the reaction can be completely completed within 3-10 minutes. If the reaction temperature is lower than 0°C and the reaction time is shorter than 3 minutes, the hydrolysis may be incomplete, which will result in incomplete hydrolysis, and some cyclization products cannot be converted, resulting in a low conversion rate of raw materials; if the reaction temperature is higher than 20°C, If the reaction time is longer than 10 min, the reaction temperature is too high, the reaction time is too long, the time cost is increased, and the cyclization product is easy to decompose, which is not conducive to the development of the reaction towards the hydrolysis reaction.
  • potassium hydroxide or an aqueous potassium hydroxide solution is usually used to perform a salt-forming reaction with the hydrolyzed product, thereby obtaining acesulfame potassium (ASK).
  • ASK acesulfame potassium
  • salt-forming reaction refers to the process in which the cation of potassium hydroxide is exchanged with the anion of the hydrolyzate to generate the potassium salt of acesulfame.
  • the ethanolic solution of potassium ethoxide is used instead of traditional potassium hydroxide or potassium hydroxide aqueous solution for salt formation reaction, and inorganic impurities including but not limited to potassium fluoride, potassium sulfate, etc.
  • the sulfonated cyclization product in the organic phase is in the reaction process with potassium ethylate, and the inorganic impurities are all dissolved in the aqueous phase, and will not be brought into the final product acesulfame potassium; in addition, the use of potassium ethylate
  • the ethanol solution neutralizes the acid ASH corresponding to acesulfame potassium, and in this process, the possible chloride of acetoacetamide and acesulfame potassium is favorably reduced, thereby blocking the source from the source during the salt formation process
  • the source of inorganic impurities thereby improving the purity of the final product acesulfame potassium, and simplifying the subsequent process to the crude product of acesulfame potassium, reducing the cost of purifying the crude product of acesulfame potassium.
  • each drug or reagent can be made by a laboratory or factory, or a commercially available product, which is not limited in this application.
  • Preparation of intermediate solution Amination reaction steps: Dissolve 98kg of sulfamic acid and the first dichloromethane at a molar ratio of 1:6, and control the dissolution temperature at about 20 to 25°C to obtain dichlorosulfamic acid Methane solution, the first reaction solution.
  • Dissolution can be in a continuous mixing device or in a reactor.
  • Acylation reaction step dissolving diketene and third dichloromethane at a molar ratio of 1:1.5, controlling the dissolution temperature at 10 to 20° C. to obtain a third reaction solution.
  • the amounts of the ammonium sulfamate solution and the third reaction solution are such that the molar ratio of ammonium sulfamate and diketene is 1:1.1. After the reaction starts, lower the temperature of the cooling water as much as possible, and control the temperature of the reaction system at 20 to 35°C; as the performance of the catalyst declines, the temperature can be slightly increased within the control range.
  • Sulfonated cyclization step dissolve sulfur trioxide in a solvent to form a cyclizing agent solution; add the cyclizing agent solution and the intermediate solution to the preset K 2 O/- ⁇ Al 2 O 3 catalyst (if necessary , please refer to Table 1) for details in the fixed-bed reactor, and control the reaction time of this step of each embodiment and comparative example to be the sulfonation cyclization reaction time shown in Table 1, obtain the sulfonation cyclization product, sulfonation The cyclization product enters the hydrolysis reactor;
  • Hydrolysis step hydrolyzing the sulfonated cyclization product with 60wt% ethanol aqueous solution to obtain a hydrolyzate solution;
  • Salt-forming step adding a salt-forming agent to the organic phase of the hydrolyzate solution to carry out a salt-forming reaction to obtain acesulfame potassium.
  • Example 1 the implementation of Comparative Example 1, the implementation of Comparative Example 2 and Comparative Example 1, the best effect was achieved in Example 1 in which the catalyst was used simultaneously in the acylation reaction and the sulfonation ring closure reaction.
  • the highest honey yield can reach 88%, and the lowest organic impurity content is 3.3ppm.
  • acylation reaction time and sulfonation reaction time are all in shorter (10-300s), and acesulfame potassium yield is higher, and organic impurity content is lower.
  • a specific solid catalyst is used for the catalytic reaction, and an acesulfame potassium composition with very little impurity content is prepared; on the one hand, in the intermediate
  • a solid acidic catalyst is used instead of traditional acetic acid, which greatly shortens the acylation reaction time, improves the reaction yield of intermediate products, reduces the organic impurities in the product, and further reduces the acesulfame potassium.
  • the catalyst in the sulfonation cyclization reaction step, adopt load-type solid base heterogeneous catalyst to catalyze, the catalyst can impel the forward progress of sulfonation cyclization step, improve the yield of sulfonation cyclization product, further Ground, improve the yield of final product acesulfame potassium; Also can reduce the content of impurity in the product simultaneously.
  • the present application can produce the acesulfame potassium composition with very little impurity content through the combined use of the two catalysts, wherein the content of the chloride of acesulfame potassium as the impurity can reach below 300ppm, greatly reducing the The post-treatment process of acesulfame potassium is improved, and the production cost of acesulfame potassium is reduced.

Abstract

提供了一种乙酰磺胺酸钾组合物，包含乙酰磺胺酸钾及其氯化物，氯化物的含量小于300ppm。该组合物采用下述方法制备：在氨基磺酸溶液中加入三乙胺，进行胺化反应，生成氨基磺酸铵盐溶液；加入双乙烯酮，在固态酸性催化剂的作用下进行酰化反应，得到中间体溶液；使中间体溶液与环化剂溶液在负载型固体碱多相催化剂的作用下发生磺化环合反应，得到磺化环合产物；水解，成盐。通过两种催化剂的结合使用，能够制得杂质含量极低的乙酰磺胺酸钾组合物，降低了乙酰磺胺酸钾后处理的工艺，降低了生产成本。

Description

乙酰磺胺酸钾组合物 技术领域
本发明属于精细化工制造技术领域，具体涉及一种乙酰磺胺酸钾组合物。
发明背景
乙酰磺胺酸钾(安赛蜜)又称AK糖，是一种广泛使用的代糖食品添加剂，外观为白色结晶性粉末，它作为一种有机合成盐，其口味与甘蔗相似，易溶于水，微溶于酒精，其化学性质稳定，不易出现分解失效现象；不参与机体代谢，不提供能量；甜度较高，价格便宜；无致龋齿性；对热和酸稳定性好。
目前在安赛蜜的合成中，普遍采用双乙烯酮-三氧化硫法，其具体的反应步骤包括：使氨基磺酸与胺反应以形成氨基磺酸胺盐，然后将氨基磺酸胺盐与双乙烯酮反应，形成乙酰基乙酰胺盐；在三氧化硫存在下，乙酰基乙酰胺盐发生环化反应，形成环状三氧化硫加合物；将环状化合物水解获得水解产物(ASH)；随后用氢氧化钾处理水解产物从而获得乙酰磺胺酸钾(ASK)。
上述制备过程中，使用了多种具有强烈反应性能的化合物，最终获得的商业化乙酰磺胺酸钾成品为乙酰磺胺酸钾与杂质的混合物，其中具有较多种类的与乙酰磺胺酸钾成分结构类似的有机物杂质。在这些有机物杂质中，部分有机物含量与乙酰磺胺酸钾非常近似，如乙酰磺胺酸钾的氯化物，且含量极为微小，采用一般方式难以将其去除，但是杂质具有较深的颜色，导致乙酰磺胺酸钾的成品呈现出浅褐色，影响了乙酰磺胺酸钾的品质。
在现有技术中虽然公开了一些对于安赛蜜合成改进的技术方法，如中国专利CN103613566B、中国专利CN111511724A以及中国专利CN112110876A。但这些技术依然无法有效提高反应的转化率、同时也不能解决环化环合产物水解后得到的产物(ASH)杂质多的问题。
发明内容
鉴于上述问题，提出了本申请以便提供一种克服上述问题或者至少部分地解决上述问题的一种乙酰磺胺酸钾组合物。
在本申请的一些实施例中，提供了一种乙酰磺胺酸钾组合物，该组合物包含乙酰磺胺酸钾和乙酰磺胺酸钾的氯化物，该乙酰磺胺酸钾组合物采用下述方法制备， 以使乙酰磺胺酸钾的氯化物的含量小于300ppm；
该方法包括：
中间体制备步骤：在氨基磺酸溶液中加入三乙胺，进行胺化反应，生成氨基磺酸铵盐溶液；向得到的氨基磺酸铵盐溶液加入双乙烯酮，在固态酸性催化剂的作用下，进行酰化反应，得到中间体溶液；
磺化环合步骤：将三氧化硫溶解在溶剂中，形成环化剂溶液；使中间体溶液与环化剂溶液在负载型固体碱多相催化剂的作用下发生磺化环合反应，得到磺化环合产物；
水解步骤：磺化环合产物与水解剂进行水解反应，得到水解产物溶液；和
成盐步骤：在水解产物溶液的有机相中加入成盐剂，进行成盐反应，得到乙酰磺胺酸钾。
可选地，在上述的乙酰磺胺酸钾组合物中，乙酰磺胺酸钾的氯化物的含量小于100ppm。
可选地，在上述的乙酰磺胺酸钾组合物中，乙酰磺胺酸钾的氯化物的含量小于10ppm。
可选地，在上述的乙酰磺胺酸钾组合物中，乙酰磺胺酸钾的氯化物的含量小于0.002-8ppm。
可选地，在制备上述的乙酰磺胺酸钾组合物的方法中，固态酸性催化剂为分子筛催化剂、固态超强酸催化剂或固态杂多酸催化剂。
可选地，在制备上述的乙酰磺胺酸钾组合物的方法中，分子筛催化剂为HZSM-5分子筛和/或Na-ZSM-5分子筛；固态超强酸催化剂为SO 4 2-/Fe 2O 3型催化剂；固态杂多酸催化剂为H 3[PMo 12O 14]·xH 2O固态催化剂。
可选地，在制备上述的乙酰磺胺酸钾组合物的方法中，负载型固体碱多相催化剂为K 2O/-γAl 2O 3催化剂，优选地，在K 2O/-γAl 2O 3催化剂中添加有机硅。
可选地，在制备上述的乙酰磺胺酸钾组合物的方法中的磺化环合步骤中，磺化环合反应的反应时间为1-15s，优选1-3s。
可选地，在制备上述的乙酰磺胺酸钾组合物的方法中的水解步骤中，水解剂为乙醇水溶液，其中，乙醇水溶液中乙醇的质量分数为60-85％。
可选地，在制备上述的乙酰磺胺酸钾组合物的方法中的成盐步骤中，成盐剂为乙醇钾的乙醇溶液，其中，乙醇钾的质量分数为10％-80％。
本申请的有益效果在于，本申请在中间体制备过程和磺化环合过程中，均采用特定的固态催化剂进行催化反应，制备出杂质含量极少的乙酰磺胺酸钾组合物；一方面，在中间体制备过程中，采用固态酸性催化剂代替传统的乙酸，极大程度上缩短了酰化反应时间、提高了中间产物的反应收率，减少了产物中的有机杂质，进一步地，降低了安赛蜜的生产成本；另一方面，在磺化环合反应步骤中采用负载型固体碱多相催化剂进行催化，催化剂能够促使磺化环合步骤的正向进行，提高磺化环合产物的收率，进一步地，提高终产物安赛蜜的收率；同时也能够降低产物中杂质的含量。本申请通过两种催化剂的结合使用，能够制得出杂质含量极少的乙酰磺胺酸钾组合物，其中，作为杂质乙酰磺胺酸钾的氯化物的含量可达300ppm以下，极大程度上，降低了乙酰磺胺酸钾后处理的工艺，降低了乙酰磺胺酸钾的生产成本。
上述说明仅是本申请技术方案的概述，为了能够更清楚了解本申请的技术手段，而可依照说明书的内容予以实施，并且为了让本申请的上述和其它目的、特征和优点能够更明显易懂，以下特举本申请的具体实施方式。
实施本发明的方式
下面将更详细地描述本申请的示例性实施例。应当理解，可以以各种形式实现本申请而不应被这里阐述的实施例所限制。相反，提供这些实施例是为了能够更透彻地理解本申请，并且能够将本申请的范围完整地传达给本领域的技术人员。
本申请的构思在于，针对安赛蜜粗产品纯度低，有机杂质含量过多，导致产品呈色较深，影响用户使用感受；后续需要复杂，成本高的后处理工艺才能达到比较理想的提纯效果的现状，本申请提供了一种乙酰磺胺酸钾组合物，该组合物采用特定的方法制得，其杂质乙酰磺胺酸钾的氯化物得含量可达到300ppm以下。
本申请提供的乙酰磺胺酸钾组合物包含乙酰磺胺酸钾和乙酰磺胺酸钾的氯化物，在该组合物中，乙酰磺胺酸钾的氯化物的含量小于300ppm，该乙酰磺胺酸钾组合物的制备方法至少包含以下步骤S110～步骤S140：
中间体制备步骤S110：在氨基磺酸溶液中加入三乙胺，进行胺化反应，生成氨基磺酸铵盐溶液；向得到的氨基磺酸铵盐溶液加入双乙烯酮，在固态酸性催化剂的作用下，进行酰化反应，得到中间体溶液。
中间体的制备更细致地分为两个小步骤，首先，是氨基磺酸铵盐的制备，然后 利用氨基磺酸铵盐与双乙烯酮反应制备中间体，即乙酰乙酰胺-N-磺酸三乙胺盐。
氨基磺酸铵盐采用的是在氨基磺酸溶液中加入三乙胺，进行胺化反应获得。具体的，在本申请的一些实施例中，在氨基磺酸溶解在第一溶剂中，配置成第一反应液；将三乙胺溶于第二溶剂，配置成第二反应液，将第二反应液加入第一反应液中进行胺化反应，形成氨基磺酸铵盐溶液。第一溶剂和第二溶剂是能够为胺化反应提供反应环境的惰性有机溶剂，如二氯甲烷。氨基磺酸和三乙胺放热反应，在反应过程中，产生的热量会将部分二氯甲烷汽化，汽化后的二氯甲烷会离开反应体系将产热带走，进一步地，汽化后的二氯甲烷也可循环利用。
在第一反应液与第二反应液混合的时候，最好将第二反应液逐渐滴入第一反应液，这样能够使得反应更加充分，不会造成局部反应物浓度过大，反应程度过于剧烈。
以下给出一种生成氨基磺酸铵盐溶液的具体实施方式，该实施方式仅作为示例性说明，氨基磺酸铵盐溶液的具体生产工艺可采用现有技术中的任意一种。按照预设的氨基磺酸、第一二氯甲烷、三乙胺和第二二氯甲烷的用量比准确称料，打开反应度的计量槽阀门向干燥的反应釜中加入第一二氯甲烷，启动搅拌及循环泵；从投料孔投入氨基磺酸。关闭循环阀门，打开送料阀门，将溶料釜中混合物料送至干燥的合成釜中，利用循环水降温，待反应釜温度降至室温(约20至25℃)，得到第一反应液。
同上述过程，得到三乙胺溶于二氯甲烷的第二反应液。
将第二反应液滴加入第一反应液中，滴加结束时，pH值为7-9，静置反应1小时，上述反应完毕的物料为氨基磺酸铵盐溶液。
在得到氨基磺酸铵盐溶液后，将氨基磺酸铵盐溶液与双乙烯酮反应，得到乙酰乙酰胺-N-磺酸三乙胺盐，作为制备安赛蜜的中间体。
现有技术中，氨基磺酸铵盐溶液与双乙烯酮反应是在乙酸的环境中进行的，在后续步骤中，乙酸很难从最终产物安赛蜜中被完全除去，残留在安赛蜜中的乙酸不仅会使安赛蜜成色不佳，而且还会带来异味。
在本申请中，采用固态酸性催化剂代替传统的乙酸有效地克服了这个问题。固态酸性催化剂能够为酰化反应提供足够的酸性位点，一方面能够有效地催化剂氨基磺酸铵盐和双乙烯酮酰化反应的顺利进行，另一方面，固态酸性催化剂不会混合到反应产物中，后续不用特殊的处理工艺，节约了后处理经济和时间成本；且避免了 现有技术中没有除掉的乙酸杂质留存在最终产物中对最终产物的品相造成的不利影响。
为了提高双乙烯酮的闪点，将双乙烯酮溶于第三溶剂中，配置成第三反应液，第三溶剂是能够为胺化反应提供反应环境的惰性有机溶剂，如二氯甲烷等。在反应器中装填固态酸性催化剂，依次向反应器加入氨基磺酸铵盐溶液和第三反应液，在预设条件下反应，形成乙酰乙酰胺-N-磺酸三乙胺盐溶液作为中间体溶液。
为了实现反应的连续性，在本申请的一些实施例中，可以选择连续反应器来实现本申请，如固定床反应器、连续搅拌釜反应器或微通道反应器等。这里以固定床反应器为例，简要说明反应过程。
在固定床反应器中装填固态酸性催化剂作为催化剂，将固定床反应器设置为预设的工作状态，先向固定床反应器通入氨基磺酸铵盐溶液，待氨基磺酸铵盐溶液正常流动后，然后再同向通入第三反应液，通过控制二者的流速，使得二者接触时间在预设条件内，同时，通过控制固定床反应器的换热装置，使得反应温度也在预设条件内，待达到预设反应时长，即可结束反应，得到产物乙酰乙酰胺-N-磺酸三乙胺盐溶液。由于固定床反应器的特点，使得本反应能够连续不断进行，适合大规模的工业生产。
磺化环合步骤S120：将三氧化硫溶解在溶剂中，形成环化剂溶液；使中间体溶液与环化剂溶液在负载型固体碱多相催化剂的作用下发生磺化环合反应，得到磺化环合产物。
在现有技术中，在磺化环合反应的步骤中，通常将乙酰基乙酰胺盐与三氧化硫直接反应，这样的反应效率不高，还会导致一些与乙酰磺胺酸钾结构类似的杂质残留到最终产物安赛蜜中，且反应收率无法达到令人满意的程度。
不同于现有技术，本申请中磺化环合步骤在负载型固体碱多相催化剂的作用下完成。催化剂能够促使磺化环合步骤的正向进行，提高磺化环合产物的收率，进一步的，提高终产物安赛蜜的收率；同时也能够降低产物中杂质的含量。
水解步骤S130：磺化环合产物与水解剂进行水解反应，得到水解产物溶液。
磺化环合产物与水解剂进行水解反应，环合产物经水解后为安赛蜜的前驱体ASH，不同于传统工艺上采用酸性溶液进行水解反应，本申请采用水解剂，水解剂能够缩短水解时间，伴随着水解时间降低的是水解可能产生的杂质含量的减少。在本申请的一些实施例中，水解剂为水或者乙醇水溶液，显著减少了环化产物ASH 中杂质的含量，降低了后续安赛蜜提纯的难度，减少了安赛蜜提纯的成本。
在本申请的一些实施例中，本申请采用了流动反应器，使得安赛蜜的制备实现了连续性，适合大规模的工艺生产。
和成盐步骤S140：在水解产物溶液的有机相中加入成盐剂，进行成盐反应，得到乙酰磺胺酸钾。
在将磺化环合产物水解后，在现有技术中，通常用氢氧化钾或氢氧化钾水溶液与水解产物进行成盐反应，从而获得乙酰磺胺酸钾(ASK)。所谓成盐反应是指氢氧化钾的阳离子与水解产物的阴离子进行交换，生成乙酰磺胺酸的钾盐的过程。
在本申请的一些实施例中，可采用成盐剂代替传统的氢氧化钾或氢氧化钾水溶液进行成盐反应，无机杂质包括但不限于氟化钾、硫酸钾等均不溶解于乙醇钾的乙醇溶液，有机相中的磺化环合产物在与成盐剂的反应过程中，无机杂质均溶解在水相中，不会带入到终产物乙酰磺胺酸钾中；另外，使用成盐剂去中和乙酰磺胺酸钾对应的酸ASH，在这个过程中，有利地减少了可能的乙酰乙酰胺和乙酰磺胺酸钾的氯化物，从而在成盐过程中，从源头上阻断了无机杂质的来源，从而提高了终产物乙酰磺胺酸钾的纯度，并简化了后续对乙酰磺胺酸钾粗产品的工艺，降低了对乙酰磺胺酸钾粗产品进行提纯的成本。在本申请的一些实施例中，成盐剂包括但不限于氢氧化钾的乙醇溶液或乙醇钾的乙醇溶液。
通过上述方法制得的乙酰磺胺酸钾组合物中，乙酰磺胺酸钾的氯化物的含量可达300ppm以下；在一些实施例中，乙酰磺胺酸钾的氯化物的含量可达100ppm以下；在另一些实施例中，乙酰磺胺酸钾的氯化物的含量可达10ppm以下；在又一些实施例中，乙酰磺胺酸钾的氯化物的含量可达0.002-8ppm。
综上所述，本申请在中间体制备过程和磺化环合过程中，均采用特定的固态催化剂进行催化反应，制备出杂质含量极少的乙酰磺胺酸钾组合物；一方面，在中间体制备过程中，采用固态酸性催化剂代替传统的乙酸，极大程度上缩短了酰化反应时间、提高了中间产物的反应收率，减少了产物中的有机杂质，进一步地，降低了安赛蜜的生产成本；另一方面，在磺化环合反应步骤中采用负载型固体碱多相催化剂进行催化，催化剂能够促使磺化环合步骤的正向进行，提高磺化环合产物的收率，进一步地，提高终产物安赛蜜的收率；同时也能够降低产物中杂质的含量。本申请通过两种催化剂的结合使用，能够制得出杂质含量极少的乙酰磺胺酸钾组合物，其中，作为杂质乙酰磺胺酸钾的氯化物的含量可达300ppm以下，极大程度上，降低 了乙酰磺胺酸钾后处理的工艺，降低了乙酰磺胺酸钾的生产成本。
固态酸性催化剂的种类
固态酸性催化剂是指能够提供酸性位点的固体催化剂，在本申请的一些实施例中，固态酸性催化剂为分子筛催化剂、固态超强酸催化剂或固态杂多酸催化剂。
分子筛具有酸碱中心，可用于酸碱催化反应。在本申请中，采用沸石催化剂代替传统的乙酸催化剂为酰化反应提供酸性位点，一方面能够有效地催化剂氨基磺酸铵盐和双乙烯酮酰化反应的顺利进行，另一方面，分子筛催化剂不会混合到反应产物中，后续不用特殊的处理工艺，节约了后处理经济和时间成本；且避免了现有技术中没有除掉的乙酸杂质留存在最终产物中对最终产物的品相造成的不利影响。
固态超强酸是酸性超过100％硫酸的酸，如用Hammett酸度函数H表示酸强度，100％硫酸的酸强度为-11.93，酸强度<-11.93的酸就是超强酸。固态酸性催化剂分为两类，一类含卤素、氟磺酸树脂成氟化物固载化物；另一类不含卤素，它由吸附在金属氧化物或氢氧化物表面的硫酸根，经高温燃烧制备。在本申请中，固态酸性催化剂的种类最好为后者，即SO 4 2-/M xO y型超强酸，其中，M表示金属原子，具体可以为Zn、Zr、Ti、Sn等，最好为SO 4 2-/Fe 2O 3型超强酸催化剂。
本申请对杂多酸催化剂的种类不做限制，凡是能够提供酸性位点的固体杂多酸催化剂均可；在本申请的一些实施例中，固态杂多酸催化剂为Keggin型结构的固态杂多酸催化剂，主要是1:12系列的Keggin型结构如H 3[PMO 12O 14]·xH 2O，它具有强酸性和氧化性，其酸性通常情况下比组成杂多酸各组分的含氧酸的酸性强，作为氧化剂时极易氧化其他物质，使自身呈还原状态而又极易再生，因此，杂多酸催化剂一方面能够有效地催化剂氨基磺酸铵盐和双乙烯酮酰化反应的顺利进行，另一方面，由于其再生能力强，显著降低了催化剂成本，进一步地，降低了安赛蜜的生产成本。
在本申请中，对固体酸性催化剂的用量不做限制，可依据反应器的规格确定。
磺化环合反应时间
在本申请的一些实施例中，对磺化环合步骤的反应时间不作限制，可参考现有技术；在本申请的另一些实施例中，在磺化环合步骤中，磺化环合反应的反应时间为1-15s，优选1-3s。为了达到在如此短的时间内，可引入文丘里反应器，使得磺化环合反应在文丘里反应器内进行，具体的，将乙酰乙酰胺-N-磺酸三乙胺盐溶液作为工作流体，将三氧化硫溶解在溶剂中，形成环化剂溶液作为引射流体；工作流 体从文丘里反应器的喷嘴进入，引射流体从文丘里反应器的吸气室进入，控制工作流体的压力高于引射流体的压力；使工作流体与引射流体在文丘里反应器的混合段和扩压段混合并进行磺化环合反应，并将磺化环合产物喷入流动反应器中。工作流体的压力为0.4-1.6MPa，引射流体的压力为0.2-1.4MPa，且工作流体的压力比引射流体的压力高0.2-0.4MPa。
水解剂的种类和水解反应条件
在本申请的一些实施例中，在上述方法中，水解剂为去离子水或乙醇水溶液，最好为乙醇的水溶液，其中，在乙醇水溶液中，乙醇的质量浓度最好为60-85％。发明人经过大量的实验，使用水解剂，尤其是乙醇的水溶液并控制水解剂中水的含量，可以明显地减少安赛蜜前驱体ASH中杂质的含量，降低了后续安赛蜜提纯的难度，减少了安赛蜜提纯的成本。
对于水解剂的用量，本申请不作限制，水解剂的用量可以根据三氧化硫的用量来确定，具体地，在本申请的一些实施例中，三氧化硫的用量与水解剂中水的含量的物质的量的比为1:1-4，在另一些实施例中，为1:1-1.5。也就是说水解剂中水的物质的量最好高于三氧化硫的物质的量。
在本申请的一些实施例中，对水解反应条件不作限制，凡是能满足水解反应需求均可；在本申请的一些实施例中，可参考现有技术；在本申请的另一些实施例中，在水解步骤中，水解反应的反应温度为-40℃至0℃，优选-20℃至0℃。也就是说，本申请的水解反应步骤优选在较低的温度进行，本申请中，温控可采用现有技术中的任意一种即可，如空气冷凝技术、循环水冷凝技术以及热量交换板等。经过反复试验，发现-40℃至0℃是水解反应的较适宜温度，若反应温度低于-40℃，则水解可能不完全，则会造成水解程度不彻底，一些环合产物不能得到转化，造成原料转化率低；若反应温度高于0℃，则反应温度过高，环合产物容易分解，不利于反应向水解反应方向发展。
通过对磺化环合步骤中反应条件的控制，使得磺化环合反应的反应时间处于1-15s，最好控制在1-3s内。
水解剂的种类和用量
在本申请的一些实施例中，在上述方法中，水解剂为去离子水或乙醇水溶液，最好为乙醇的水溶液，其中，在乙醇水溶液中，乙醇的质量浓度最好为30～65％。发明人经过大量的实验，使用水解剂，尤其是乙醇的水溶液并控制水解剂中水的含 量，可以明显地减少安赛蜜前驱体ASH中杂质的含量，降低了后续安赛蜜提纯的难度，减少了安赛蜜提纯的成本。
对于水解剂的用量，本申请不作限制，水解剂的用量可以根据三氧化硫的用量来确定，具体地，在本申请的一些实施例中，三氧化硫的用量与水解剂中水的含量的物质的量的比为1:1-4，在另一些实施例中，为1:1-1.5。也就是说水解剂中水的物质的量最好高于三氧化硫的物质的量。
水解反应条件
在本申请中，对于水解反应条件不作限制，凡是能满足水解反应需求均可；在本申请的一些实施例中，在水解反应步骤中，反应温度设为0至20℃，在又一些实施例中为10至20℃；反应时间设为3-10min。也就是说，本申请的水解反应步骤优选在较低的温度进行，由于二氯甲烷能够带走大量的产热，因此，本申请中，温控是较容易实现的，采用现有技术中的任意一种即可，如空气冷凝技术、循环水冷凝技术以及热量交换板等。由于本申请采用了固态酸性催化剂，能够显著缩短水解反应步骤的反应时间，在3-10min即可较为彻底地完成反应。若反应温度低于0℃，反应时间短于3min，则水解可能不完全，则会造成水解程度不彻底，一些环合产物不能得到转化，造成原料转化率低；若反应温度高于20℃，反应时间长于10min，则反应温度过高，反应时间过长，增加时间成本，且环合产物容易分解，不利于反应向水解反应方向发展。
成盐剂的种类
在现有技术中，在得到磺化环合产物后，通常用氢氧化钾或氢氧化钾水溶液与水解产物进行成盐反应，从而获得乙酰磺胺酸钾(ASK)。所谓成盐反应是指氢氧化钾的阳离子与水解产物的阴离子进行交换，生成乙酰磺胺酸的钾盐的过程。
在本申请的一些实施例中，采用乙醇钾的乙醇溶液代替传统的氢氧化钾或氢氧化钾水溶液进行成盐反应，无机杂质包括但不限于氟化钾、硫酸钾等均不溶解于乙醇钾的乙醇溶液，有机相中的磺化环合产物在与乙醇钾的反应过程中，无机杂质均溶解在水相中，不会带入到终产物乙酰磺胺酸钾中；另外，使用乙醇钾的乙醇溶液去中和乙酰磺胺酸钾对应的酸ASH，在这个过程中，有利地减少了可能的乙酰乙酰胺和乙酰磺胺酸钾的氯化物，从而在成盐过程中，从源头上阻断了无机杂质的来源，从而提高了终产物乙酰磺胺酸钾的纯度，并简化了后续对乙酰磺胺酸钾粗产品的工艺，降低了对乙酰磺胺酸钾粗产品进行提纯的成本。
对于上述其他未提及的反应物料的用量以及反应条件，均可参考现有技术，如中国专利CN112142687A等。
药品或试剂来源
在本申请中，各药品或试剂均可采用实验室或者工厂自制，也可采用市售产品，本申请不作限制。
实施例
实施对比例1～对比例1
中间体溶液的制备：胺化反应步骤：将98kg氨基磺酸和第一二氯甲烷以摩尔比为1：6的比例溶解，控制溶解温度约为20至25℃，获得氨基磺酸的二氯甲烷溶液，即第一反应液。溶解可以在连续混合装置中，也可以在反应釜中。
将三乙胺和第二二氯甲烷以摩尔比为1：1的比例溶解，控制溶解的温度为10至30℃，得到第二反应液，其中，氨基磺酸和三乙胺的质量比为1:1.2。将第二反应液逐渐滴加在第一反应液所在的反应釜中进行混合搅拌，控制体系温度为20至30℃，并控制体系呈弱碱性，混合均匀后，即得到氨基磺酸铵盐溶液。
酰化反应步骤：将双乙烯酮和第三二氯甲烷以摩尔比为1：1.5的比例溶解，控制溶解的温度为10至20℃，得到第三反应液。
将催化剂安装至固定床反应器后(如有，具体请参见表1)，启动固定床反应器，调节循环水使循环水工作正常。
将氨基磺酸铵盐溶液通入固定床反应器内，在氨基磺酸铵盐溶液正常流动后，将第三反应液与氨基磺酸铵盐溶液同向通入固定床反应器内，控制氨基磺酸铵盐溶液和第三反应液的量，使得氨基磺酸铵盐和双乙烯酮摩尔比为1：1.1。在反应开始后，尽量调低冷却水温度，反应体系的温度控制在20至35℃；随着催化剂性能的衰退，温度在控制范围内可以略微升高。
控制氨基磺酸铵盐溶液和双乙烯酮的流速，使得各实施例或者对比例的该步骤的反应时间被控制为在表1所示的酰化反应时间，得到的目标产物乙酰乙酰胺-N-磺酸三乙胺盐溶液，即中间体溶液，中间体溶液进入下一个固定床反应器。
磺化环合步骤：将三氧化硫溶解在溶剂中，形成环化剂溶液；将环化剂溶液与中间体溶液对向加入到预设有K 2O/-γAl 2O 3催化剂(如需，具体请参见表1)固定床反应器中，并控制各实施例和对比例的该步骤的反应时间为在表1所示的磺化环 合反应时间，得到磺化环合产物，磺化环合产物进入水解反应器；
水解步骤：使磺化环合产物与60wt％乙醇水溶液进行水解反应，得到水解产物溶液；
成盐步骤：在水解产物溶液的有机相中加入成盐剂，进行成盐反应，得到乙酰磺胺酸钾。
表1：
Figure PCTCN2021097010-appb-000001
从实施例1、实施对比例1、实施对比例2和对比例1中可以看出，在酰化反应和磺化环合反应同时使用催化剂的实施例1中取得了最好的效果，安赛蜜收率最高可达88％，有机杂质含量最低为3.3ppm。从实施例1中还可以看出，酰化反应 时间和磺化反应时间均在较短(10-300s)内，安赛蜜收率较高，有机杂质含量较低。
从实施对比例1和实施对比例2可以看出，在催化剂存在的情况下，能够显著缩短酰化反应或者磺化环合反应的反应时间，缩短反应时间，能够极大程度上降低终产物中有机杂质的含量。
从对比例1可以看出，在两个步骤均不使用催化剂的情况下，在反应时间均在3600s的情况下，安赛蜜的收率仅达到65％，有机杂质含量为5830ppm。
综上所述，本申请在中间体制备过程和磺化环合过程中，均采用特定的固态催化剂进行催化反应，制备出杂质含量极少的乙酰磺胺酸钾组合物；一方面，在中间体制备过程中，采用固态酸性催化剂代替传统的乙酸，极大程度上缩短了酰化反应时间、提高了中间产物的反应收率，减少了产物中的有机杂质，进一步地，降低了安赛蜜的生产成本；另一方面，在磺化环合反应步骤中采用负载型固体碱多相催化剂进行催化，催化剂能够促使磺化环合步骤的正向进行，提高磺化环合产物的收率，进一步地，提高终产物安赛蜜的收率；同时也能够降低产物中杂质的含量。本申请通过两种催化剂的结合使用，能够制得出杂质含量极少的乙酰磺胺酸钾组合物，其中，作为杂质乙酰磺胺酸钾的氯化物的含量可达300ppm以下，极大程度上，降低了乙酰磺胺酸钾后处理的工艺，降低了乙酰磺胺酸钾的生产成本。
以上所述，仅为本申请的具体实施方式，在本申请的上述教导下，本领域技术人员可以在上述实施例的基础上进行其他的改进或变形。本领域技术人员应该明白，上述的具体描述只是更好地解释本申请的目的，本申请的保护范围应以权利要求的保护范围为准。
此外，本领域的技术人员能够理解，尽管在此所述的一些实施例包括其它实施例中所包括的某些特征而不是其它特征，但是不同实施例的特征的组合意味着处于本申请的范围之内并且形成不同的实施例。例如，在下面的权利要求书中，所要求保护的实施例的任意之一都可以以任意的组合方式来使用。

Claims (10)

  1. 一种乙酰磺胺酸钾组合物，其特征在于，所述组合物包含乙酰磺胺酸钾和乙酰磺胺酸钾的氯化物，所述乙酰磺胺酸钾组合物采用下述方法制备，以使乙酰磺胺酸钾的氯化物的含量小于300ppm；
    所述方法包括：
    中间体制备步骤：在氨基磺酸溶液中加入三乙胺，进行胺化反应，生成氨基磺酸铵盐溶液；向得到的氨基磺酸铵盐溶液加入双乙烯酮，在固态酸性催化剂的作用下，进行酰化反应，得到中间体溶液；
    磺化环合步骤：将三氧化硫溶解在溶剂中，形成环化剂溶液；使所述中间体溶液与所述环化剂溶液在负载型固体碱多相催化剂的作用下发生磺化环合反应，得到磺化环合产物；
    水解步骤：使所述磺化环合产物与水解剂进行水解反应，得到水解产物溶液；和
    成盐步骤：在所述水解产物溶液的有机相中加入成盐剂，进行成盐反应，得到乙酰磺胺酸钾。
  2. 根据权利要求1所述的乙酰磺胺酸钾组合物，其特征在于，所述乙酰磺胺酸钾的氯化物的含量小于100ppm。
  3. 根据权利要求2所述的乙酰磺胺酸钾组合物，其特征在于，所述乙酰磺胺酸钾的氯化物的含量小于10ppm。
  4. 根据权利要求3所述的乙酰磺胺酸钾组合物，其特征在于，所述乙酰磺胺酸钾的氯化物的含量小于0.002-8ppm。
  5. 根据权利要求1所述的乙酰磺胺酸钾组合物，其特征在于，所述固态酸性催化剂为分子筛催化剂、固态超强酸催化剂或固态杂多酸催化剂。
  6. 根据权利要求5所述的乙酰磺胺酸钾组合物，其特征在于，所述分子筛催化剂为HZSM-5分子筛和/或Na-ZSM-5分子筛；所述固态超强酸催化剂为SO 4 2-/Fe 2O 3型催化剂；所述固态杂多酸催化剂为H 3[PMo 12O 14]·xH 2O固态催化剂。
  7. 根据权利要求1所述的乙酰磺胺酸钾组合物，其特征在于，所述负载型固体碱多相催化剂为K 2O/-γAl 2O 3催化剂，优选地，在K 2O/-γAl 2O 3催化剂中添加有机硅。
  8. 根据权利要求1所述的乙酰磺胺酸钾组合物，其特征在于，在所述磺化环合步骤中，所述磺化环合反应的反应时间为1-15s，优选1-3s。
  9. 根据权利要求1所述的乙酰磺胺酸钾组合物，其特征在于，在所述水解步骤中，所述水解剂为乙醇水溶液，其中，所述乙醇水溶液中乙醇的质量分数为60-85％。
  10. 根据权利要求1所述的乙酰磺胺酸钾组合物，其特征在于，在所述成盐步骤中，所述成盐剂为乙醇钾的乙醇溶液，其中，乙醇钾的质量分数为10％-80％。
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104411693A (zh) * 2012-06-08 2015-03-11 鹿特诺瓦营养品和食品有限公司 用于生产乙酰磺胺酸钾的方法
CN111377882A (zh) * 2018-12-30 2020-07-07 南通醋酸化工股份有限公司 一种连续化生产安赛蜜的方法
CN111511724A (zh) * 2017-12-15 2020-08-07 化工咨询股份有限公司(德国) 在具有特定流速的喷雾反应器中制备安赛蜜的方法

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3531359A1 (de) * 1985-09-03 1987-03-12 Hoechst Ag Verfahren zur herstellung von 6-methyl-3,4-dihydro-1,2,3-oxathiazin-4-on-2,2-dioxid sowie zu dessen reinigung
PT3319949T (pt) * 2016-09-21 2020-10-12 Celanese Int Corp Composições de acessulfame de potássio e processos para produzir o mesmo
HUE055805T2 (hu) * 2016-09-21 2021-12-28 Celanese Int Corp Aceszulfám-kálium kompozíciók és eljárások ezek elõállítására
CN107835807A (zh) * 2016-09-21 2018-03-23 国际人造丝公司 乙酰舒泛钾组合物和其生产方法
DK3322695T3 (da) * 2016-09-21 2020-09-28 Celanese Int Corp Acesulfam-kalium-sammensætninger og fremgangsmåder til fremstilling af disse

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104411693A (zh) * 2012-06-08 2015-03-11 鹿特诺瓦营养品和食品有限公司 用于生产乙酰磺胺酸钾的方法
CN111511724A (zh) * 2017-12-15 2020-08-07 化工咨询股份有限公司(德国) 在具有特定流速的喷雾反应器中制备安赛蜜的方法
CN111377882A (zh) * 2018-12-30 2020-07-07 南通醋酸化工股份有限公司 一种连续化生产安赛蜜的方法

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
"Inorganic and Analytical Chemistry Experiments", 28 February 2007, HIGHER EDUCATION PRESS, CN, ISBN: 978-7-04-020551-0, article NI, JINGAN ET AL.: "Experiment 89: Preparation and Characterization of Solid Superacid", pages: 1 - 3, XP009543004 *
MA QIANLI; SUO YANHUA; MENG FANLONG; ZHANG WEI; WANG YINGJUN: "Research Advance in Modification and Application of SO42-/MxOy Solid Superacid Catalyst", INDUSTRIAL CATALYSIS, NORTHWEST RESEARCH INSTITUTE OF CHEMICAL INDUSTRY, CHINA, vol. 22, no. 2, 1 February 2014 (2014-02-01), China , pages 85 - 91, XP009541276, ISSN: 1008-1143, DOI: 10.3969/j.issn.1008-1143.2014.02.002 *
X. DUAN ET AL.: "Synthesis of Acesulfame Potassium", FINE CHEMICALS, vol. 13, no. 5, 1 January 1996 (1996-01-01), pages 22 - 24, XP055436957, ISSN: 1003-5214, DOI: 10.13550/j .jxhg.1996.05.007 *

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