WO2022246871A1 - 乙酰乙酰胺-n-磺酸三乙胺盐的制备方法 - Google Patents

乙酰乙酰胺-n-磺酸三乙胺盐的制备方法 Download PDF

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WO2022246871A1
WO2022246871A1 PCT/CN2021/097019 CN2021097019W WO2022246871A1 WO 2022246871 A1 WO2022246871 A1 WO 2022246871A1 CN 2021097019 W CN2021097019 W CN 2021097019W WO 2022246871 A1 WO2022246871 A1 WO 2022246871A1
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reaction
solution
triethylamine
sulfamic acid
dichloromethane
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PCT/CN2021/097019
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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/CN2021/097019 priority Critical patent/WO2022246871A1/zh
Priority to CN202180001415.9A priority patent/CN113454056B/zh
Publication of WO2022246871A1 publication Critical patent/WO2022246871A1/zh

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J29/00—Catalysts comprising molecular sieves
    • B01J29/04—Catalysts comprising molecular sieves having base-exchange properties, e.g. crystalline zeolites
    • B01J29/06—Crystalline aluminosilicate zeolites; Isomorphous compounds thereof
    • B01J29/40—Crystalline aluminosilicate zeolites; Isomorphous compounds thereof of the pentasil type, e.g. types ZSM-5, ZSM-8 or ZSM-11, as exemplified by patent documents US3702886, GB1334243 and US3709979, respectively
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C211/00—Compounds containing amino groups bound to a carbon skeleton
    • C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
    • C07C211/02—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
    • C07C211/03—Monoamines
    • C07C211/05—Mono-, di- or tri-ethylamine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/34—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfuric acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C307/00—Amides of sulfuric acids, i.e. compounds having singly-bound oxygen atoms of sulfate groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C307/02—Monoamides of sulfuric acids or esters thereof, e.g. sulfamic acids
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/584—Recycling of catalysts

Definitions

  • the invention belongs to the technical field of fine chemicals, and in particular relates to a preparation method of acetoacetamide-N-sulfonic acid triethylamine salt.
  • 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.
  • Acetoacetamide-N-sulfonic acid triethylamine salt is the important intermediate of producing acesulfame potassium, and the preparation method of this intermediate generally adopts diketene-sulfur trioxide method, and its specific reaction steps comprise: 1) making sulfamic acid Reaction with an amine to form the amine sulfamate salt, which is then reacted with diketene to form the acetoacetamide-N-sulfonic acid triethylamine salt.
  • the above reaction uses common sulfamic acid, diketene, triethylamine, etc. as raw materials.
  • the reaction conditions are mild, the product yield is high, and the product purity is high. It is a relatively common industrialized method.
  • acylation reaction between sulfamic acid amine salt and diketene is a strong exothermic reaction, diketene has a low flash point, and high-concentration diketene is prone to accidents at high temperatures.
  • the addition acylation reaction must be carried out under strict temperature control conditions.
  • the reaction speed is slow, the reaction time is prolonged, and ice water cooling is required during the reaction process, which increases the reaction cost; the reaction requires a specific device, and the device cost and device maintenance cost are high; large-scale reactions cannot be completed in time and are not suitable for industrialization Continuous production.
  • acetic acid needs to be added as a catalyst in the reaction process, which makes acetic acid impurities remain in the final product acesulfame potassium, resulting in poor color of acesulfame potassium, and the color is brown or brownish yellow, which reduces the value of the product.
  • the application is proposed so as to provide a kind of preparation method of acetoacetamide-N-sulfonic acid triethylamine salt that overcomes the above-mentioned problems or at least partially solves the above-mentioned problems.
  • a kind of preparation method of acetoacetamide-N-sulfonic acid triethylamine salt comprising:
  • Amination reaction steps dissolving sulfamic acid in the first dichloromethane to configure the first reaction solution; dissolving triethylamine in the second dichloromethane to configure the second reaction solution, adding the second reaction solution to Amination reaction is carried out in the first reaction solution to form ammonium sulfamate solution; and
  • Acylation reaction step fill the zeolite catalyst in the fixed bed reactor, pass the sulfamic acid ammonium salt solution and diketene into the fixed bed reactor in turn, and react under the preset conditions to form acetoacetamide-N-sulfonic acid triethyl Amine salt solution.
  • the ratio of the molar amount of sulfamic acid to the molar amount of the first dichloromethane is 1:6-15; the dissolution of sulfamic acid The temperature is 20-25°C.
  • the ratio of the molar amount of triethylamine to the molar amount of the second dichloromethane is 1:1-1.2; -30 °C soluble in the second dichloromethane.
  • the ratio of the mass consumption of sulfamic acid to the mass consumption of triethylamine is 1:1-1.2; the reaction temperature of the amination reaction is 20-30°C.
  • the ratio of the molar amount of sulfamic acid to the molar amount of diketene is 1:1.02-1.1.
  • the preset conditions are: the temperature is set at 15-25° C.; the reaction time is set at 10-120 s.
  • the preset conditions are: the temperature is set at 18-22°C; the reaction time is set at 30-120s.
  • the zeolite catalyst is ZSM-5 molecular sieve.
  • the ZSM-5 molecular sieve is HZSM-5 molecular sieve and/or Na-ZSM-5 molecular sieve.
  • acetoacetamide-N-sulfonic acid triethylamine salt which is prepared by any of the methods described above.
  • the beneficial effect of the present application is that the present application uses a solid-state zeolite catalyst combined with a fixed-bed reactor to replace the traditional technical solution of an organic acid catalyst combined with a reaction tank. Better, it significantly improves the user experience; on the other hand, it realizes the large-scale continuous production of acetoacetamide-N-sulfonic acid triethylamine salt, which greatly shortens the reaction time and improves the reaction yield. Further, Reduced the production cost of acesulfame potassium.
  • the intermediate acetoacetamide-N-sulfonic acid triethylamine salt for the preparation of acesulfame potassium has long reaction time, low reaction efficiency, low product yield, and difficulty in controlling the reaction temperature.
  • the problem of providing a kind of preparation method of acetoacetamide-N-sulfonic acid triethylamine salt, is used for producing acetoacetamide-N-sulfonic acid triethylamine salt by combining a solid zeolite catalyst with a fixed bed reactor can effectively overcome the above problems, realize continuous large-scale production, shorten the reaction time, and improve production efficiency.
  • the preparation method of acetoacetamide-N-sulfonic acid triethylamine salt of the present application comprises:
  • Amination reaction steps dissolving sulfamic acid in the first dichloromethane to configure the first reaction solution; dissolving triethylamine in the second dichloromethane to configure the second reaction solution, adding the second reaction solution to Amination reaction is carried out in the first reaction solution to form ammonium sulfamate solution.
  • sulfamic acid ammonium salt specifically, sulfamic acid and triethylamine are dissolved in methylene chloride respectively, sulfamic acid and triethylamine exothermic reaction, in the reaction process, the heat that produces will Part of the dichloromethane is vaporized, and the vaporized dichloromethane will leave the reaction system to take away the heat produced. Further, the vaporized dichloromethane can also be recycled.
  • the first reaction solution and the second reaction solution obtained by dissolving sulfamic acid and triethylamine in dichloromethane respectively are subjected to an amination reaction to obtain a sulfamic acid ammonium salt solution.
  • 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.
  • dichloromethane by mixing dichloromethane with the raw materials sulfamic acid and triethylamine respectively, and then reacting with diketene, dichloromethane can take away a large amount of reaction heat on the one hand, making temperature control easier ; On the other hand, it can improve the flash point of diketene and improve the reaction temperature of the whole reaction.
  • a zeolite catalyst is filled in a fixed bed reactor, ammonium sulfamate solution and diketene are introduced into the fixed bed reactor in turn, and react under preset conditions to form acetoacetamide-N-sulfonic acid tris Ethylamine salt solution.
  • zeolite catalysts are selected. Zeolite catalysts are also called molecular sieve catalysts. Molecular sieves have acid-base centers and can be used for acid-base catalytic reactions. In this application, the zeolite catalyst is used to replace the traditional acetic acid catalyst to provide acidic sites for the acylation reaction. On the one hand, 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. .
  • This application also adopts a fixed bed reactor.
  • the type and specification of the fixed bed reactor there are no restrictions on the type and specification of the fixed bed reactor.
  • the molecular sieve catalyst can be fixed, there is no need to provide a liquid acidic environment and no impurities are introduced during the reaction. , such as a tubular fixed-bed reactor.
  • the reaction can be ended by preset reaction time, 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.
  • the beneficial effect of the present application is that the present application uses a solid-state zeolite catalyst combined with a fixed-bed reactor to replace the traditional technical solution of an organic acid catalyst combined with a reaction tank.
  • the user experience has been significantly improved; on the other hand, large-scale continuous production of acetoacetamide-N-sulfonic acid triethylamine salt has been realized, the reaction time has been greatly shortened, the reaction yield has been improved, and further, the The production cost of acesulfame potassium.
  • the type of zeolite catalyst is not limited, and any solid zeolite catalyst that can provide acid sites can be used; in some embodiments of the application, the zeolite catalyst is a ZSM-5 molecular sieve; in some implementations of the application In an example, in the above method, the ZSM-5 molecular sieve is HZSM-5 molecular sieve and/or Na-ZSM-5 molecular sieve.
  • ZSM-5 molecular sieve is a new type of zeolite molecular sieve containing organic amine cations, especially HZSM-5 molecular sieve and Na-ZSM-5 molecular sieve.
  • this application uses ZSM-5 molecular sieve, and further uses HZSM-5 molecular sieve and/or Na-ZSM-5 molecular sieve as a preferred solution.
  • the ratio of the amount of sulfamic acid to the first dichloromethane is not limited, as long as the complete dissolution of sulfamic acid is ensured; in some embodiments of the present application Among them, considering economic factors, the ratio of the molar dosage of sulfamic acid to the molar dosage of the first dichloromethane is 1:6-15.
  • the dissolution temperature of sulfamic acid in the first dichloromethane is 20-25°C, that is, at room temperature. If the temperature is lower than 20°C or higher than 25°C, it only needs to be realized by specific means, although it is possible to achieve more Rapid dissolution, but requires a high economic cost, because the sulfamic acid is not difficult to dissolve, so it can be at room temperature.
  • the ratio of the amount of triethylamine to the second dichloromethane is not limited, as long as the complete dissolution of triethylamine is ensured; in this application Considering economical factors in some embodiments of the application, in the amination reaction step, the ratio of the molar amount of triethylamine to the molar amount of the second dichloromethane is 1:1-1.2.
  • the temperature at which triethylamine is dissolved in the second dichloromethane can be set at 10-30°C, and under low temperature conditions, it is beneficial to dissipate heat during the dissolution process.
  • the ratio of the amount of sulfamic acid to triethylamine is not limited, and prior art can be referred to.
  • the ratio of the mass usage of sulfamic acid to the mass usage of triethylamine is 1:1-1.2.
  • the temperature of the amination reaction since the amination reaction does not need heating or cooling, it can be carried out at room temperature, and in some embodiments of the present application, it can be 20-30°C.
  • the ratio of the amount of sulfamic acid to triethylamine is not limited, and prior art can be referred to, such as in Chinese patent document CN112142687A, sulfamic acid and triethylamine
  • n(sulfamic acid) of diketene:n(diketene) 1:1.0-1.5.
  • diketene needs a large surplus to achieve better technical results.
  • sulfamic acid and diketene have greater contact area, to obtain a better mixing effect, so that the upper limit of the amount of diketene relative to the prior art can be reduced, in some embodiments of the application, in the above-mentioned method, the ratio of the molar amount of sulfamic acid to the molar amount of diketene is 1:1.02-1.1.
  • the preset conditions in the acylation reaction step there is no limit to the preset conditions in the acylation reaction step, as long as there is no danger and can meet the reaction requirements of ammonium sulfamate solution and diketene; in some embodiments of the application , in the acylation reaction step, the preset conditions are: the temperature is set at 15-25°C; the reaction time is set at 10-120s. That is to say, the acylation reaction step of the present application is preferably carried out at a lower temperature, because dichloromethane can take away a large amount of heat, therefore, in the present application, temperature control is easier to achieve, using the prior art Any one of them can be used, such as air condensation technology, circulating water condensation technology and heat exchange plate.
  • the reaction time of the acylation step can be significantly shortened, and the reaction can be completely completed within 10-120 seconds. If the reaction temperature is lower than 15°C and the reaction time is shorter than 10s, the reaction conditions are difficult to control, resulting in high reaction costs, too short contact time of raw materials, and incomplete reaction; if the reaction temperature is higher than 25°C and the reaction time is longer than 120s, then If the reaction temperature is too high, it is prone to danger, and the reaction time is too long, which increases the time cost and has no other beneficial effects; in other embodiments of the present application, in the acylation reaction step, the preset condition can preferably be: temperature Set it to 18-22°C; set the reaction time to 30-120s.
  • each drug or reagent can be made by a laboratory or factory, or a commercially available product, which is not limited in this application.
  • Embodiment 1 (comprising embodiment 1A, embodiment 1B, embodiment 1C, implementing comparative example 1D, implementing comparative example 1E)
  • Amination reaction steps 98kg of sulfamic acid and the first dichloromethane are dissolved in a molar ratio of 1:6, and the dissolution temperature is controlled at about 20-25°C to obtain the dichloromethane solution of sulfamic acid as the first reaction liquid.
  • Dissolution can be in a continuous mixing device or in a reactor.
  • Embodiment 1A, embodiment 1B, embodiment 1C, embodiment 1D, embodiment 1E all comprise amination reaction step, in this reaction step, between each embodiment, the mass ratio of sulfamic acid and triethylamine changes, Please see Table 1 for details.
  • Acylation reaction steps set zeolite molecular sieve in the fixed bed reactor, use Na-ZSM-5 molecular sieve for zeolite molecular screening, after the zeolite molecular sieve is installed in the fixed bed reactor, adjust the circulating water to make the circulating water work normally.
  • Control the amount of sulfamic acid ammonium salt solution and diketene, calculated as the molar ratio of sulfamic acid and diketene in the sulfamic acid ammonium salt solution is 1:1.02-1.1; control the reaction time of the sulfamic acid ammonium salt solution and diketene, time control Between 10-120 seconds.
  • the solution of the obtained target product acetoacetamide-N-sulfonic acid triethylamine salt is subjected to conventional methods such as suction filtration and crystallization to obtain the solid target product.
  • Embodiment 1A, embodiment 1B, embodiment 1C, embodiment 1D, embodiment 1E all comprise acylation reaction step, in this reaction step, between each embodiment, the molar ratio of sulfamic acid and diketene and reaction conditions exist change , see Table 1 for details.
  • Embodiment 2 (comprising embodiment 2A, embodiment 2B, embodiment 2C, implementing comparative example 2D, implementing comparative example 2E)
  • Amination reaction steps 98kg of sulfamic acid and the first dichloromethane are dissolved in a molar ratio of 1:15, and the temperature of dissolution is controlled to be about 20-25°C to obtain the dichloromethane solution of sulfamic acid as the first reaction liquid.
  • Dissolution can be in a continuous mixing device or in a reactor.
  • Embodiment 1A, embodiment 1B, embodiment 1C, embodiment 1D, embodiment 1E all comprise amination reaction step, in this reaction step, between each embodiment, the mass ratio of sulfamic acid and triethylamine changes, Please see Table 1 for details.
  • Acylation reaction step set zeolite molecular sieve in fixed bed reactor, zeolite molecular sieve uses H-ZSM-5 molecular sieve, after zeolite molecular sieve is installed in fixed bed reactor, adjust circulating water to make circulating water work normally.
  • Control the amount of sulfamic acid ammonium salt solution and diketene, calculated as the molar ratio of sulfamic acid and diketene in the sulfamic acid ammonium salt solution is 1:1.02-1.1; control the reaction time of the sulfamic acid ammonium salt solution and diketene, time control Between 10-120 seconds.
  • the solution of the obtained target product acetoacetamide-N-sulfonic acid triethylamine salt is subjected to conventional methods such as suction filtration and crystallization to obtain the solid target product.
  • Embodiment 1A, embodiment 1B, embodiment 1C, embodiment 1D, embodiment 1E all comprise acylation reaction step, in this reaction step, between each embodiment, the molar ratio of sulfamic acid and diketene and reaction conditions exist change , see Table 1 for details.
  • Comparative Example 1 (comprising Comparative Example 1A and Comparative Example 1B)
  • Amination reaction step 98kg of sulfamic acid and triethylamine are mixed and stirred in a reaction kettle with a mass ratio of 1:1, and the control system is weakly alkaline. After mixing evenly, the ammonium sulfamic acid solution is obtained.
  • the configuration of the dichloromethane solution of diketene dissolve diketene and dichloromethane at a molar ratio of 1:8, and dichloromethane solution of diketene.
  • Comparative Example 2 (comprising Comparative Example 2A, Comparative Example 2B, Comparative Example 2C, Comparative Example 2D and Comparative Example 2E)
  • Amination reaction steps 98kg of sulfamic acid and the first dichloromethane are dissolved in a molar ratio of 1:15, and the temperature of dissolution is controlled to be about 20-25°C to obtain the dichloromethane solution of sulfamic acid as the first reaction liquid.
  • Dissolution can be in a continuous mixing device or in a reactor.
  • Comparative Example 2A, Comparative Example 2B, Comparative Example 2C, Comparative Example 2D and Comparative Example 2E all comprise an amination reaction step, and in this reaction step, between each embodiment, the mass ratio of sulfamic acid and triethylamine varies, Please see Table 1 for details.
  • Acylation reaction step adopt fixed bed reactor, but do not use zeolite molecular sieve.
  • the sulfamic acid ammonium salt solution after adding acetic acid is passed in the fixed-bed reactor, controls the flow velocity of the sulfamic acid ammonium salt solution; Diketene is passed in the fixed-bed reactor, controls the diketene flow velocity; After the reaction begins, adjust as far as possible The cooling water temperature is low, and the temperature of the reaction system is controlled between 15°C and 25°C; as the activity of the zeolite molecular sieve decreases, the temperature rises slightly within the control range.
  • Control the amount of sulfamic acid ammonium salt solution and diketene, calculated as the molar ratio of sulfamic acid and diketene in the sulfamic acid ammonium salt solution is 1:1.02-1.1; control the reaction time of the sulfamic acid ammonium salt solution and diketene, time control Between 10-120 seconds.
  • the solution of the obtained target product acetoacetamide-N-sulfonic acid triethylamine salt is subjected to conventional methods such as suction filtration and crystallization to obtain the solid target product.
  • the results in Comparative Example 2 are listed in Table 1.
  • the yield is based on sulfamic acid, and the calculation method of the yield is the percentage of the mass of the target product acetoacetamide-N-sulfonic acid triethylamine salt to the mass of sulfamic acid.
  • embodiment 1 and embodiment 2 have used HZSM-5 molecular sieve or Na-ZSM-5 molecular sieve, and reaction temperature can be controlled between 15-25 °C, and in fixed-bed reactor, reaction can Done quickly.
  • the advantage of completing the reaction quickly is that under the same production capacity, a relatively small amount of diketene can be added at a time to meet the needs of subsequent production. From the reaction point of view, the whole reaction time should not be too long, and the longer maintenance time will cause the decline of the overall yield.
  • the reaction in some examples of Example 1 and Example 2 can be completed within 30 seconds, with higher yield, faster reaction, and fast reaction, thereby avoiding the potential safety hazard of diketene.
  • the slow reaction speed requires larger reaction equipment and more reactant input for the same output, which is uneconomical for production, and a large number of reactants means higher risk and longer time for The overall yield is not favorable.
  • this application uses a solid-state zeolite catalyst combined with a fixed-bed reactor to replace the traditional technical solution of an organic acid catalyst combined with a reaction tank.
  • it simplifies the post-treatment process of the product, making the final product acesulfame potassium better.
  • Significantly improved user experience; on the other hand, large-scale continuous production of acetoacetamide-N-sulfonic acid triethylamine salt has been realized, which greatly shortens the reaction time, improves the reaction yield, and further reduces the safety The production cost of semi honey.

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Abstract

一种乙酰乙酰胺-N-磺酸三乙胺盐的制备方法，包括：将氨基磺酸溶解在第一二氯甲烷中，配置成第一反应液；将三乙胺溶于第二二氯甲烷中，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；在固定床反应器中装填沸石催化剂，依次向所述固定床反应器通入所述氨基磺酸铵盐溶液和双乙烯酮，在预设条件下反应，形成乙酰乙酰胺-N-磺酸三乙胺盐溶液。所述方法简化了产物后处理过程，使得最终产品安赛蜜的品相更好，显著提升了使用感受；另一方面，实现了乙酰乙酰胺-N-磺酸三乙胺盐大规模连续生产，极大程度上缩短了反应时间、提高了反应收率，进一步的，降低了安赛蜜的生产成本。

Description

乙酰乙酰胺-N-磺酸三乙胺盐的制备方法 技术领域
本发明属于精细化工技术领域，具体涉及一种乙酰乙酰胺-N-磺酸三乙胺盐的制备方法。
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。
乙酰乙酰胺-N-磺酸三乙胺盐是生产安赛蜜重要的中间体，该中间体的制备方法普遍采用双乙烯酮-三氧化硫法，其具体的反应步骤包括：1)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，形成乙酰乙酰胺-N-磺酸三乙胺盐。
上述反应以常见的氨基磺酸、双乙烯酮、三乙胺等为原料，反应条件温和，产品收率较高，产物纯度高，是一种比较常见的工业化方法。但由于氨基磺酸胺盐与双乙烯酮的酰化反应是强放热反应，双乙烯酮的闪点低，高浓度的双乙烯酮在高温下容易发生事故，加成酰化反应必须在严格的温控条件下进行，反应速度缓慢，反应时间延长，在反应过程中还需要冰水降温，增加了反应成本；反应需要特定的装置，装置成本、装置维护维修成本高；大批量的反应无法及时完成，不适合工业化连续化生产。另一方面，在反应过程中需要加入乙酸作为催化剂，这使得乙酸杂质会留存在最终产品安赛蜜中，导致安赛蜜成色不好，颜色显示为棕色或者棕黄色，使得产品价值降低。
现有技术中也有关注到双乙烯酮闪点较低的问题，中国专利申请CN105198778A将二氯甲烷与双乙烯酮使用，以提升了酰化反应的温度，缩短反应时间，提高了生产效率。但是仍然存在着反应速度慢、反应时间长、收率低的问题，不能满足大规模连续生产的需求；且仍然没有脱离对乙酸的依赖。
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乙酰胺-N-磺酸三乙胺盐的制备方法。
根据本申请的一方面，提供了一种乙酰乙酰胺-N-磺酸三乙胺盐的制备方法，包括：
胺化反应步骤：将氨基磺酸溶解在第一二氯甲烷中，配置成第一反应液；将三乙胺溶于第二二氯甲烷，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；和
酰化反应步骤：在固定床反应器中装填沸石催化剂，依次向固定床反应器通入氨基磺酸铵盐溶液和双乙烯酮，在预设条件下反应，形成乙酰乙酰胺-N-磺酸三乙胺盐溶液。
在本申请的一些实施例中，在上述方法中，在胺化反应步骤中，氨基磺酸的摩尔用量与第一二氯甲烷的摩尔用量的比为1:6-15；氨基磺酸的溶解温度为20-25℃。
在本申请的一些实施例中，在上述方法中，在胺化反应步骤中，三乙胺的摩尔用量与第二二氯甲烷的摩尔用量的比为1:1-1.2；三乙胺在10-30℃溶于第二二氯甲烷。
在本申请的一些实施例中，在上述方法中，在胺化反应步骤中，氨基磺酸的质量用量与三乙胺的质量用量的比为1:1-1.2；胺化反应的反应温度为20-30℃。
在本申请的一些实施例中，在上述方法中，氨基磺酸的摩尔用量与双乙烯酮的摩尔用量的比为1：1.02-1.1。
在本申请的一些实施例中，在上述方法中，在酰化反应步骤中，预设条件为：温度设为15-25℃；反应时间设为10-120s。
在本申请的一些实施例中，在上述方法中，在酰化反应步骤中，预设条件为：温度设为18-22℃；反应时间设为30-120s。
在本申请的一些实施例中，在上述方法中，沸石催化剂为ZSM-5分子筛。
在本申请的一些实施例中，在上述方法中，ZSM-5分子筛为HZSM-5分子筛和/或Na-ZSM-5分子筛。
根据本申请的另一方面，提供了一种乙酰乙酰胺-N-磺酸三乙胺盐，其是采用上述任一所述的方法制备而得的。
本申请的有益效果在于，本申请通过采用固态的沸石催化剂结合固定床反应器代替传统的有机酸催化剂结合反应罐的技术方案，一方面简化了产物后处理过程，使得最终产品安赛蜜品相更好，显著提升了使用感受；另一方面，实现了乙酰乙酰 胺-N-磺酸三乙胺盐大规模连续生产，极大程度上缩短了反应时间、提高了反应收率，进一步地，降低了安赛蜜的生产成本。
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。虽然显示了本申请的示例性实施例，然而应当理解，可以以各种形式实现本申请而不应被这里阐述的实施例所限制。相反，提供这些实施例是为了能够更透彻地理解本申请，并且能够将本申请的范围完整地传达给本领域的技术人员。
本申请的构思在于，针对现有技术中，制备安赛蜜的中间体乙酰乙酰胺-N-磺酸三乙胺盐存在着反应时间长、反应效率低、产品收率低、反应温度难以控制的问题，提供了一种乙酰乙酰胺-N-磺酸三乙胺盐的制备方法，通过将固体沸石催化剂与固定床反应器结合起来用于生产乙酰乙酰胺-N-磺酸三乙胺盐，能够有效克服上述问题，实现了连续大规模生产，缩短了反应时间，提高了生产效率。
本申请的乙酰乙酰胺-N-磺酸三乙胺盐的制备方法包括：
胺化反应步骤：将氨基磺酸溶解在第一二氯甲烷中，配置成第一反应液；将三乙胺溶于第二二氯甲烷，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。
首先，是氨基磺酸铵盐的制备，具体的，将氨基磺酸和三乙胺分别溶于二氯甲烷中，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，进一步的，汽化后的二氯甲烷也可循环利用。
将氨基磺酸和三乙胺分别溶于二氯甲烷得到的第一反应液和第二反应液进行胺化反应，得到氨基磺酸铵盐溶液。
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℃)，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。
本申请的一些实施例中，通过将二氯甲烷与原料氨基磺酸和三乙胺分别混合，然后再与双乙烯酮反应，二氯甲烷一方面能够带走反应大量的热，使得温控更容易进行；另一方面能提高双乙烯酮的闪点，提高整个反应的反应温度。
和酰化反应步骤：在固定床反应器中装填沸石催化剂，依次向固定床反应器通入氨基磺酸铵盐溶液和双乙烯酮，在预设条件下反应，形成乙酰乙酰胺-N-磺酸三乙胺盐溶液。
在本申请中选用的是固态的沸石催化剂，沸石催化剂又称分子筛催化剂，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。
本申请还采用固定床反应器，在本申请中对固定床反应器的类型、规格不做限制，凡是能够实现对分子筛催化剂的固定，从而在反应中不用提供液态酸性环境且不引入杂质即可，如列管式固定床反应器。
在固定床反应器中装填沸石催化剂，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，然后再同向通入双乙烯酮，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。
本申请的有益效果在于，本申请采用固态的沸石催化剂结合固定床反应器代替传统的有机酸催化剂结合反应罐的技术方案，一方面简化了产物后处理过程，使得最终产品安赛蜜品相更好，显著提升了使用感受；另一方面，实现了乙酰乙酰胺-N-磺酸三乙胺盐大规模连续生产，极大程度上缩短了反应时间、提高了反应收率，进一步地，降低了安赛蜜的生产成本。
沸石分子筛的种类和用量
在本申请中，对沸石催化剂的种类不做限制，凡是能够提供酸性位点的固体沸石催化剂均可；在本申请的一些实施例中，沸石催化剂为ZSM-5分子筛；在本申请的一些实施例中，在上述方法中，ZSM-5分子筛为HZSM-5分子筛和/或Na-ZSM-5分子筛。
ZSM-5分子筛是一种含有机胺阳离子的新型沸石分子筛，尤其是HZSM-5分子筛和Na-ZSM-5分子筛，由于在化学组成、晶体结构及物化性质方面具有许多独特性，因此显示出了优异的催化效能，本申请将ZSM-5分子筛，进一步地将HZSM-5分子筛和/或Na-ZSM-5分子筛作为一种优选方案。
在本申请中，对沸石催化剂的用量不做限制，可依据固定床反应器的规格确定。
氨基磺酸与第一二氯甲烷的用量比
这里需要说明的是，在本申请中，出现了第一二氯甲烷和第二二氯甲烷的写法，这里的“第一”和“第二”仅作为区分标识，不具有任何实际意义。
在本申请中，在胺化反应步骤中，对氨基磺酸与第一二氯甲烷的用量比不做限定，在保障将氨基磺酸完全溶解的情况下即可；在本申请的一些实施例中，考虑到经济因素，氨基磺酸的摩尔用量与第一二氯甲烷的摩尔用量的比为1:6-15。
氨基磺酸在第一二氯甲烷中的溶解温度为20-25℃，即在室温条件下即可，若温度低于20℃或高于25℃仅需要采用特定的手段实现，虽然可能实现更加迅速的溶解，但是需要较高的经济代价，由于氨基磺酸溶解并不困难，因此在室温条件下即可。
三乙胺与第二二氯甲烷的用量比
在本申请中，在上述方法中，在胺化反应步骤中，对三乙胺与第二二氯甲烷的用量比不做限定，在保障将三乙胺完全溶解的情况下即可；在本申请的一些实施例中考虑到经济因素，在胺化反应步骤中，三乙胺的摩尔用量与第二二氯甲烷的摩尔用量的比为1:1-1.2。
三乙胺溶于第二二氯甲烷的温度可设置在10-30℃，在低温条件下，有利于溶解过程的散热。
氨基磺酸与三乙胺的用量比
在本申请中，在胺化反应步骤中，对氨基磺酸与三乙胺的用量比不做限定，可参考现有技术，在本申请中，为了提高氨基磺酸的转化率，可采用略微过量的三乙胺，在本申请的一些实施例中，氨基磺酸的质量用量与三乙胺的质量用量的比为1:1-1.2。
胺化反应的反应温度
在本申请中，对胺化反应的温度不做限制，由于胺化反应无需加热也无需冷却，因此可在室温条件下进行，在本申请的一些实施例中，可为20-30℃。
氨基酸酸与双乙烯酮的用量比
在本申请中，在上述方法中，在胺化反应步骤中，对氨基磺酸与三乙胺的用量比例不做限定，可参考现有技术，如在中国专利文献CN112142687A中，氨基磺酸和双乙烯酮的摩尔比例n(氨基磺酸)：n(双乙烯酮)＝1：1.0-1.5。
在现有技术中，双乙烯酮是需要大量过剩，才能取得比较好的技术效果，在本申请中，由于采用了固态沸石催化剂与固定床反应器的结合，使得氨基磺酸与双乙烯酮具有更大的接触面积，获得更好的混合效果，使得双乙烯酮相对现有技术的用量上限可以得到降低，在本申请的一些实施例中，在上述方法中，氨基磺酸的摩尔用量与双乙烯酮的摩尔用量的比为1：1.02-1.1。
预设条件
在本申请中，对于酰化反应步骤中的预设条件不做限制，凡是在不发生危险，且能满足氨基磺酸铵盐溶液与双乙烯酮的反应需求均可；在本申请的一些实施例中，在酰化反应步骤中，预设条件为：温度设为15-25℃；反应时间设为10-120s。也就是说，本申请的酰化反应步骤优选在较低的温度下进行，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。由于本申请的采用了固态沸石催化剂与固定床反应器的结合方法，能够显著缩短酰化反应步骤的反应时间，在10-120s即可较为彻底地完成反应。若反应温度低于15℃，反应时间短于10s，则反应条件较难控制，造成反应成本高，原料接触时间过短，反应不完全；若反应温度高于25℃，反应时间长于120s，则反应温度过高，容易发生危险，反 应时间过长，增加时间成本，且不具有其他有益效果；在本申请的另一些实施例中，在酰化反应步骤中，预设条件可以优选为：温度设为18-22℃；反应时间设为30-120s。
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，本申请不做限制。
实施例1(包含实施例1A、实施例1B、实施例1C、实施对比例1D、实施对比例1E)
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20-25℃，获得氨基磺酸的二氯甲烷溶液为第一反应液。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10-30℃，得到第二反应液，其中，氨基磺酸和三乙胺的质量比为1:1-1.2。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，控制体系呈弱碱性。混合均匀后，即得到氨基磺酸铵盐溶液。
实施例1A、实施例1B、实施例1C、实施例1D、实施例1E均包含胺化反应步骤，在该反应步骤中，各实施例间，氨基磺酸和三乙胺的质量比存在变化，请详见表1。
酰化反应步骤:在固定床反应器内设置沸石分子筛，沸石分子筛选用Na-ZSM-5分子筛，将沸石分子筛安装至固定床反应器后，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，控制氨基磺酸铵盐溶液的流速；将双乙烯酮通入固定床反应器内，控制双乙烯酮流速；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15℃-25℃之间；随着沸石分子筛活性的降低，温度在控制范围内略微升高。
控制氨基磺酸铵盐溶液和双乙烯酮的量，以氨基磺酸铵盐溶液中氨基磺酸和双乙烯酮摩尔比为1：1.02-1.1计算；控制氨基磺酸铵盐溶液和双乙烯酮的反应时间，时间控制在10-120秒之间。得到的目标产物乙酰乙酰胺-N-磺酸三乙胺盐的溶液经过抽滤、结晶等常规方法得到固态目标产物。
实施例1A、实施例1B、实施例1C、实施例1D、实施例1E均包含酰化反应 步骤，在该反应步骤中，各实施例间，氨基磺酸和双乙烯酮的摩尔比以及反应条件存在变化，请详见表1。
需要说明的是，在上述实施例中出现的温度值，由于反应过程是放热的，因此温度控制在上述的温度范围内即可，需要精确控制在某一温度下，凡是在上述的温度范围内，均可实现本申请，以下在各实施例中不再逐一说明。
实施例2(包含实施例2A、实施例2B、实施例2C、实施对比例2D、实施对比例2E)
胺化反应步骤:将98kg氨基磺酸和第一二氯甲烷以摩尔比为1：15的比例溶解，控制溶解温度约为20-25℃，获得氨基磺酸的二氯甲烷溶液为第一反应液。溶解可以在连续混合装置中，也可以在反应釜中。将三乙胺和二氯甲烷以摩尔比为1：1.2的比例溶解，控制溶解的温度为10-30℃，得到第二反应液，其中，氨基磺酸和三乙胺的质量比为1:1-1.2。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，控制体系呈弱碱性。混合均匀后，即得到氨基磺酸铵盐溶液。
实施例1A、实施例1B、实施例1C、实施例1D、实施例1E均包含胺化反应步骤，在该反应步骤中，各实施例间，氨基磺酸和三乙胺的质量比存在变化，请详见表1。
酰化反应步骤:在固定床反应器内设置沸石分子筛，沸石分子筛选用H-ZSM-5分子筛，将沸石分子筛安装至固定床反应器后，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，控制氨基磺酸铵盐溶液的流速；将双乙烯酮通入固定床反应器内，控制双乙烯酮流速；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15℃-25℃之间；随着沸石分子筛活性的降低，温度在控制范围内略微升高。
控制氨基磺酸铵盐溶液和双乙烯酮的量，以氨基磺酸铵盐溶液中氨基磺酸和双乙烯酮摩尔比为1：1.02-1.1计算；控制氨基磺酸铵盐溶液和双乙烯酮的反应时间，时间控制在10-120秒之间。得到的目标产物乙酰乙酰胺-N-磺酸三乙胺盐的溶液经过抽滤、结晶等常规方法得到固态目标产物。
实施例1A、实施例1B、实施例1C、实施例1D、实施例1E均包含酰化反应步骤，在该反应步骤中，各实施例间，氨基磺酸和双乙烯酮的摩尔比以及反应条件存在变化，请详见表1。
对比例1(包含对比例1A和对比例1B)
胺化反应步骤：将98kg氨基磺酸和三乙胺按照质量比为1:1在的反应釜中进行混合搅拌，控制体系呈弱碱性，混合均匀后，即得到氨基磺酸铵盐溶液。
双乙烯酮的二氯甲烷溶液的配置：将双乙烯酮与二氯甲烷以摩尔比为1：8的比例溶解，双乙烯酮的二氯甲烷溶液。
酰化反应步骤：采用固定床反应器，在本对比例中不采用任何催化剂。
将氨基磺酸铵盐溶液通入固定床反应器内，控制氨基磺酸铵盐溶液的流速，将双乙烯酮通入固定床反应器内，控制双乙烯酮流速；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34℃-45℃之间。得到的目标产物乙酰乙酰胺-N-磺酸三乙胺盐的溶液经过抽滤、结晶等常规方法得到固态目标产物。将对比例1中的结果列于表1。
在对比例1中，由于使用了双乙烯酮的二氯甲烷溶液，因此闪点提高，提高了安全性。酰化反应为放热反应，反应温度升高到40℃以后，二氯甲烷开始汽化，从而带走部分热量，整体反应时间相较控制在双乙烯酮闪点以下的反应而言，有明显降低，使用二氯甲烷汽化控制温度还存在着控温不可靠和由于有机物气体外泄带来的环保问题。
从表1中可以看出，对比例1中，反应需要维持更长的反应时间才能获得更高的收率，更长的反应时间、更高的反应温度通常会伴随更多的副反应发生。
对比例2(包含对比例2A、对比例2B、对比例2C、对比例2D和对比例2E)
胺化反应步骤:将98kg氨基磺酸和第一二氯甲烷以摩尔比为1：15的比例溶解，控制溶解温度约为20-25℃，获得氨基磺酸的二氯甲烷溶液为第一反应液。溶解可以在连续混合装置中，也可以在反应釜中。将三乙胺和二氯甲烷以摩尔比为1：1.2的比例溶解，控制溶解的温度为10-30℃，得到第二反应液，其中，氨基磺酸和三乙胺的质量比为1:1-1.2。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，控制体系呈弱碱性。混合均匀后，即得到氨基磺酸铵盐溶液。
对比例2A、对比例2B、对比例2C、对比例2D和对比例2E均包含胺化反应步骤，在该反应步骤中，各实施例间，氨基磺酸和三乙胺的质量比存在变化，请详见表1。
酰化反应步骤：采用固定床反应器，但不使用沸石分子筛。
在氨基磺酸铵盐溶液内滴加与按照与氨基磺酸：乙酸摩尔比为1：0.05计算得出的乙酸的量。
将添加乙酸后的氨基磺酸铵盐溶液通入固定床反应器内，控制氨基磺酸铵盐溶液的流速；将双乙烯酮通入固定床反应器内，控制双乙烯酮流速；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15℃-25℃之间；随着沸石分子筛活性的降低，温度在控制范围内略微升高。
控制氨基磺酸铵盐溶液和双乙烯酮的量，以氨基磺酸铵盐溶液中氨基磺酸和双乙烯酮摩尔比为1：1.02-1.1计算；控制氨基磺酸铵盐溶液和双乙烯酮的反应时间，时间控制在10-120秒之间。得到的目标产物乙酰乙酰胺-N-磺酸三乙胺盐的溶液经过抽滤、结晶等常规方法得到固态目标产物。将对比例2中的结果列于表1。
从表1中可以看出，在对比例2的条件下，由于反应温度低，反应时间短(120s之内)，反应很难进行彻底，乙酰乙酰胺-N-磺酸三乙胺盐的收率非常低。
表1
Figure PCTCN2021097019-appb-000001
Figure PCTCN2021097019-appb-000002
注：收率是以氨基磺酸计，收率的计算方法是，目标产物乙酰乙酰胺-N-磺酸三乙胺盐的质量占氨基磺酸的质量的百分比。
从表1中可以看出，实施例1和实施例2使用了HZSM-5分子筛或Na-ZSM-5分子筛，反应温度能够控制在15-25℃之间，在固定床反应器中，反应可以快速完成。快速完成反应的好处是在同等产能下，单次可以添加相对少的量的双乙烯酮即可满足后续生产需要。从反应来看，整个反应时间不宜过长，维持时间更长，将会引起整体收率的下降。实施例1和实施例2的部分实施例中的反应中能够30秒内完成反应，收率更高，反应更快，反应快从而避免了双乙烯酮的安全隐患。在连续化生产中，反应速度慢对于同等的产量需要更大型的反应设备和更多的反应物投入，这对于生产不经济，并且大量的反应物意味着更高的风险，时间维持更久对于 整体收率并不是有利的。
综上所述，本申请采用固态的沸石催化剂结合固定床反应器代替传统的有机酸催化剂结合反应罐的技术方案，一方面简化了产物后处理过程，使得最终产品安赛蜜品相更好，显著提升了使用感受；另一方面，实现了乙酰乙酰胺-N-磺酸三乙胺盐大规模连续生产，极大程度地缩短了反应时间、提高了反应收率，进一步地，降低了安赛蜜的生产成本。
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的解释本申请的目的，本申请的保护范围应以权利要求的保护范围为准。
此外，本领域的技术人员能够理解，尽管在此所述的一些实施例包括其它实施例中所包括的某些特征而不是其它特征，但是不同实施例的特征的组合意味着处于本申请的范围之内并且形成不同的实施例。例如，在下面的权利要求书中，所要求保护的实施例的任意之一都可以以任意的组合方式来使用。

Claims (10)

  1. 一种乙酰乙酰胺-N-磺酸三乙胺盐的制备方法，其特征在于，包括：
    胺化反应步骤：将氨基磺酸溶解在第一二氯甲烷中，配置成第一反应液；将三乙胺溶于第二二氯甲烷，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；和
    酰化反应步骤：在固定床反应器中装填沸石催化剂，依次向所述固定床反应器通入所述氨基磺酸铵盐溶液和双乙烯酮，在预设条件下反应，形成乙酰乙酰胺-N-磺酸三乙胺盐溶液。
  2. 根据权利要求1所述的方法，其特征在于，在所述胺化反应步骤中，所述氨基磺酸的摩尔用量与所述第一二氯甲烷的摩尔用量的比为1:6-15；所述氨基磺酸的溶解温度为20-25℃。
  3. 根据权利要求1所述的方法，其特征在于，在所述胺化反应步骤中，所述三乙胺的摩尔用量与所述第二二氯甲烷的摩尔用量的比为1:1-1.2；所述三乙胺在10-30℃溶于第二二氯甲烷。
  4. 根据权利要求1所述的方法，其特征在于，在所述胺化反应步骤中，所述氨基磺酸的质量用量与所述三乙胺的质量用量的比为1:1-1.2；所述胺化反应的反应温度为20-30℃。
  5. 根据权利要求1所述的方法，其特征在于，所述氨基磺酸的摩尔用量与所述双乙烯酮的摩尔用量的比为1：1.02-1.1。
  6. 根据权利要求1所述的方法，其特征在于，在所述酰化反应步骤中，所述预设条件为：温度设为15-25℃；反应时间设为10-120s。
  7. 根据权利要求1所述的方法，其特征在于，在所述酰化反应步骤中，所述预设条件为：温度设为18-22℃；反应时间设为30-120s。
  8. 根据权利要求1所述的方法，其特征在于，所述沸石催化剂为ZSM-5分子筛。
  9. 根据权利要求8所述的方法，其特征在于，所述ZSM-5分子筛为HZSM-5分子筛和/或Na-ZSM-5分子筛。
  10. 一种乙酰乙酰胺-N-磺酸三乙胺盐，其特征在于，其是采用权利要求1～9中任一项所述的方法制备而得的。
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