阅读说明：本技术 乙酰乙酰胺-n-磺酸三乙胺盐的制备方法 (Preparation method of acetoacetamide-N-sulfonic acid triethylamine salt ) 是由 周睿 丁震 陈永旭 杨峰宝 刘刚 于 2021-05-28 设计创作，主要内容包括：本申请公开了一种乙酰乙酰胺-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,得到第一反应液；将三乙胺溶于第二二氯甲烷,得到第二反应液,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：将双乙烯酮溶于第三二氯甲烷,配置成第三反应液；在固定床反应器中装填固态杂多酸催化剂,依次向固定床反应器通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。本申请简化了产物后处理过程,使得最终产品安赛蜜品相更好；且实现了乙酰乙酰胺-N-磺酸三乙胺盐大规模连续生产,缩短了反应时间、提高了反应收率,降低了安赛蜜的生产成本。(The application discloses a preparation method of acetoacetamide-N-sulfonic triethylamine salt, which comprises the following steps: amination reaction step: dissolving sulfamic acid in first dichloromethane to obtain a first reaction solution; dissolving triethylamine in second dichloromethane to obtain second reaction liquid, and adding the second reaction liquid into the first reaction liquid to carry out amination reaction to form ammonium sulfamate solution; and an acylation reaction step: dissolving diketene in third dichloromethane to prepare a third reaction solution; and filling a solid heteropolyacid catalyst in the fixed bed reactor, sequentially introducing an ammonium sulfamate solution and a third reaction solution into the fixed bed reactor, and reacting under a preset condition to form the acetoacetamide-N-sulfonic acid triethylamine salt. The method simplifies the post-treatment process of the product, so that the acesulfame potassium of the final product is better in phase; and the large-scale continuous production of the acetoacetamide-N-sulfonic acid triethylamine salt is realized, the reaction time is shortened, the reaction yield is improved, and the production cost of the acesulfame is reduced.)

1. A preparation method of acetoacetamide-N-sulfonic triethylamine salt is characterized by comprising the following steps:

amination reaction step: dissolving sulfamic acid in first dichloromethane to prepare a first reaction solution; dissolving triethylamine in second dichloromethane to prepare a second reaction solution, and adding the second reaction solution into the first reaction solution to carry out amination reaction to form an ammonium sulfamate solution; and

and (3) acylation reaction: dissolving diketene in third dichloromethane to prepare a third reaction solution; and filling a solid heteropoly acid catalyst in the fixed bed reactor, sequentially introducing the ammonium sulfamate solution and the third reaction solution into the fixed bed reactor, and reacting under preset conditions to form the acetoacetamide-N-triethylamine sulfonate solution.

2. The method according to claim 1, wherein in the amination step, the ratio of the molar amount of sulfamic acid to the molar amount of the first dichloromethane is 1:6 to 15; the dissolving temperature of the sulfamic acid is 20-25 ℃.

3. The method according to claim 1, wherein in the amination step, the ratio of the molar amount of the triethylamine to the molar amount of the second dichloromethane is 1: 1.5-2.5; the triethylamine is dissolved in second dichloromethane at 10-20 ℃.

4. The method according to claim 1, characterized in that, in the amination step,

the ratio of the mass usage of the sulfamic acid to the mass usage of the triethylamine is 1: 1-1.2; the reaction temperature of the amination reaction is 20-30 ℃.

5. The process according to claim 1, wherein in the acylation step, the ratio of the molar amount of diketene to the molar amount of third dichloromethane is 1: 1.5-2.5;

the diketene is dissolved in third dichloromethane at 10-20 ℃.

6. The process according to claim 1, characterized in that the ratio of the molar amount of sulfamic acid to the molar amount of diketene is 1:1-1.2, preferably 1: 1.02-1.1.

7. The method according to claim 1, wherein in the acylation reaction step, the preset conditions are: the temperature is set to be 20-35 ℃, preferably 25-30 ℃; the reaction time is set to 10 to 120s, preferably 30 to 120 s.

8. The process of claim 1, wherein the solid heteropolyacid catalyst is a Keggin-type structured solid heteropolyacid catalyst.

9. The method of claim 8, wherein the first and second light sources are selected from the group consisting of,characterized in that the Keggin type structure solid heteropoly acid catalyst is H₃[PMo₁₂O₁₄]·xH₂O a solid catalyst.

10. An acetoacetamide-N-sulfonic acid triethylamine salt characterized in that it is prepared by the process of any of claims 1 to 9.

Technical Field

The invention belongs to the technical field of fine chemical engineering, and particularly relates to a preparation method of acetoacetamide-N-sulfonic acid triethylamine salt.

Background

Acesulfame potassium (acesulfame potassium) is also called AK sugar, it is a kind of sugar substitute food additive used extensively, the appearance is white crystalline powder, it is an organic synthetic salt, its taste is similar to sugarcane, easy to dissolve in water, slightly soluble in alcohol, its chemical property is stable, it is difficult to appear decomposing and losing efficacy; does not participate in the metabolism of the organism and does not provide energy; the sweetness is higher, and the price is low; no cariogenic property; has good stability to heat and acid.

The acetoacetamide-N-sulfonic acid triethylamine salt is an important intermediate for producing acesulfame, the preparation method of the intermediate generally adopts a diketene-sulfur trioxide method, and the specific reaction steps comprise: 1) reacting sulfamic acid with an amine to form an amine sulfamate salt, and then reacting the amine sulfamate salt with diketene to form the acetoacetamide-N-sulfonic acid triethylamine salt.

The reaction takes common sulfamic acid, diketene, triethylamine and the like as raw materials, has mild reaction conditions, higher product yield and high product purity, and is a common industrial method. However, because the acylation reaction of the amine sulfamate and the diketene is a strong exothermic reaction, the flash point of the diketene is low, the high-concentration diketene is easy to cause accidents at high temperature, the addition acylation reaction must be carried out under strict temperature control conditions, the reaction speed is slow, the reaction time is prolonged, ice water is required for cooling in the reaction process, and the reaction cost is increased; the reaction needs a special device, so that the device cost and the device maintenance cost are high; the large-batch reaction can not be completed in time, and is not suitable for industrialized continuous production. On the other hand, acetic acid is required to be added as a catalyst in the reaction process, so that acetic acid impurities can remain in the final product acesulfame, the color of the acesulfame is poor, and the use feeling of people is influenced.

In the prior art, the problem of low flash point of diketene is also noticed, and the Chinese patent application CN105198778A uses dichloromethane and diketene to improve the temperature of acylation reaction, shorten the reaction time and improve the production efficiency. But still has the problems of slow reaction speed, long reaction time and low yield, and can not meet the requirement of large-scale continuous production; and still does not escape the dependence on acetic acid.

Disclosure of Invention

In view of the above problems, the present application has been made to provide a method for preparing a triethylamine salt of acetoacetamide-N-sulfonate, which overcomes or at least partially solves the above problems.

According to an aspect of the present application, a method for preparing acetoacetamide-N-sulfonic acid triethylamine salt comprises:

amination reaction step: dissolving sulfamic acid in first dichloromethane to prepare a first reaction solution; dissolving triethylamine in second dichloromethane to prepare a second reaction solution, and adding the second reaction solution into the first reaction solution to carry out amination reaction to form an ammonium sulfamate solution; and

and (3) acylation reaction: dissolving diketene in third dichloromethane to prepare a third reaction solution; and filling a solid heteropoly acid catalyst in the fixed bed reactor, sequentially introducing an ammonium sulfamate solution and a third reaction solution into the fixed bed reactor, and reacting under a preset condition to form an acetoacetamide-N-triethylamine sulfonate salt solution.

In some embodiments of the present application, in the above process, the ratio of the molar amount of sulfamic acid to the molar amount of first dichloromethane in the amination step is 1:6 to 15; the dissolving temperature of the sulfamic acid is 20-25 ℃.

In some embodiments of the present application, in the above process, the ratio of the molar amount of triethylamine to the molar amount of second dichloromethane in the amination step is 1: 1.5-2.5; triethylamine was dissolved in second dichloromethane at 10-20 ℃.

In some embodiments of the present application, in the above process, the ratio of the mass amount of sulfamic acid to the mass amount of triethylamine in the amination step is 1:1 to 1.2; the reaction temperature of the amination reaction is 20-30 ℃.

In some embodiments of the present application, in the above process, the ratio of the molar amount of diketene to the molar amount of third dichloromethane in the acylation reaction step is 1: 1.5-2.5;

diketene is dissolved in third dichloromethane at 10-20 ℃.

In some embodiments of the present application, in the above process, the ratio of the molar amount of sulfamic acid to the molar amount of diketene is 1:1-1.2, preferably 1: 1.02-1.1.

In some embodiments of the present application, in the above method, in the acylation reaction step, the preset conditions are: the temperature is set to be 20-35 ℃, preferably 25-30 ℃; the reaction time is set to 10 to 120s, preferably 30 to 120 s.

In some embodiments of the present application, in the above process, the solid heteropolyacid catalyst is a Keggin-type structured solid heteropolyacid catalyst.

In some embodiments of the present application, in the above process, the solid heteropolyacid catalyst of a Keggin-type structure is H₃[PMo₁₂O₁₄]·xH₂O a solid catalyst.

According to another aspect of the present application, there is provided an acetoacetamide-N-sulfonic acid triethylamine salt prepared by the method of any one of the above.

The method has the beneficial effects that the technical scheme that the traditional organic acid catalyst is combined with the reaction tank by combining the solid heteropoly acid catalyst with the fixed bed reactor instead of the traditional organic acid catalyst is adopted, so that on one hand, the post-treatment process of the product is simplified, the acesulfame honey product phase of the final product is better, and the use experience is obviously improved; on the other hand, the large-scale continuous production of the acetoacetamide-N-sulfonic acid triethylamine salt is realized, the reaction time is greatly shortened, the reaction yield is improved, and the production cost of the acesulfame is further reduced.

The foregoing description is only an overview of the technical solutions of the present application, and the present application can be implemented according to the content of the description in order to make the technical means of the present application more clearly understood, and the following detailed description of the present application is given in order to make the above and other objects, features, and advantages of the present application more clearly understandable.

Detailed Description

Exemplary embodiments of the present application will be described in more detail below. While exemplary embodiments of the present application have been illustrated, it should be understood that the present application may be embodied in various forms and should not be limited by the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the disclosure to those skilled in the art.

The conception of the application lies in that aiming at the problems of long reaction time, low reaction efficiency, low product yield and difficult control of reaction temperature in the prior art for preparing the intermediate acetoacetamide-N-sulfonic acid triethylamine salt of acesulfame, the preparation method of the acetoacetamide-N-sulfonic acid triethylamine salt is provided, and the problems can be effectively overcome by combining a solid zeolite catalyst and a fixed bed reactor for producing the acetoacetamide-N-sulfonic acid triethylamine salt, so that the continuous large-scale production is realized, the reaction time is shortened, and the production efficiency is improved.

The preparation method of the acetoacetamide-N-sulfonic acid triethylamine salt comprises the following steps:

amination reaction step: dissolving sulfamic acid in first dichloromethane to prepare a first reaction solution; and dissolving triethylamine in second dichloromethane to prepare a second reaction solution, and adding the second reaction solution into the first reaction solution to carry out amination reaction to form an ammonium sulfamate solution.

Firstly, the ammonium sulfamate is prepared, specifically, sulfamic acid and triethylamine are respectively dissolved in dichloromethane, the sulfamic acid and the triethylamine are subjected to exothermic reaction, in the reaction process, part of dichloromethane is vaporized by generated heat, the vaporized dichloromethane leaves a reaction system to remove heat, and further, the vaporized dichloromethane can be recycled.

And respectively dissolving sulfamic acid and triethylamine in dichloromethane to obtain a first reaction solution and a second reaction solution, and carrying out amination reaction to obtain an ammonium sulfamate solution.

When first reaction liquid mixes with the second reaction liquid, best with the second reaction liquid dropwisely into first reaction liquid gradually, can make the reaction more abundant like this, can not cause local reactant concentration too big, the reaction degree is too violent.

A specific embodiment of the formation of the ammonium sulfamate solution is given below, and this embodiment is merely an illustrative example, and any of the prior art techniques may be used for the specific production process of the ammonium sulfamate solution. Accurately weighing materials according to the preset dosage ratio of sulfamic acid, first dichloromethane, triethylamine and second dichloromethane, opening a valve of a measuring tank for reactivity to add the first dichloromethane into a dry reaction kettle, and starting a stirring and circulating pump; sulfamic acid is fed from a feeding hole. And (3) closing the circulating valve, opening the feeding valve, feeding the mixed materials in the dissolving kettle into a dry synthesis kettle, cooling by using circulating water, and obtaining a first reaction liquid when the temperature of the reaction kettle is reduced to room temperature (about 20 ℃).

In the same way as the above process, a second reaction solution of triethylamine dissolved in dichloromethane was obtained.

And dropwise adding the second reaction solution into the first reaction solution, keeping the pH value at 7-9 after the dropwise adding is finished, and standing for 1 hour to react, wherein the material after the reaction is the ammonium sulfamate solution.

It should be noted that, in the present application, the writing of the first dichloromethane, the second dichloromethane and the third dichloromethane appears, and the "first", "second" and "third" are merely used as distinguishing labels and do not have any practical meaning.

In some embodiments of the application, dichloromethane is mixed with sulfamic acid and triethylamine as raw materials respectively and then reacts with diketene dissolved in dichloromethane, so that dichloromethane can take away a large amount of heat of reaction on one hand, and temperature control is easier to perform; on the other hand, the flash point of the diketene can be increased, and the reaction temperature of the whole reaction is increased.

And an acylation reaction step: dissolving diketene in third dichloromethane to prepare a third reaction solution; and filling a solid heteropoly acid catalyst in the fixed bed reactor, sequentially introducing an ammonium sulfamate solution and a third reaction solution into the fixed bed reactor, and reacting under a preset condition to form an acetoacetamide-N-triethylamine sulfonate salt solution.

In the application, a solid heteropoly acid catalyst is selected, the heteropoly acid catalyst is a catalyst containing oxygen bridge multi-core coordination compounds, and a certain gap is formed between heteropoly ions in a solid heteropoly acid catalyst body phase, so that some molecules can enter and exit, and the solid heteropoly acid can smoothly complete a catalytic process.

In the application, the solid heteropoly acid catalyst is adopted to replace the traditional acetic acid catalyst to provide an acid site for acylation reaction, so that on one hand, the amino sulfonic acid ammonium salt and diketene acylation reaction can be effectively catalyzed to be smoothly carried out, on the other hand, the solid heteropoly acid catalyst cannot be mixed into a reaction product, a special treatment process is not needed in the subsequent process, and the post-treatment economy and the time cost are saved; and avoids the adverse effect of acetic acid impurities which are not removed in the prior art and remain in the final product on the quality phase of the final product.

The application still adopts fixed bed reactor, does not do the restriction to fixed bed reactor's type, specification in the application, all can realize the fixed to solid-state heteropoly acid catalyst to need not provide liquid acid environment and not introduce impurity in the reaction can, like shell and tube fixed bed reactor.

Filling a solid heteropoly acid catalyst in a fixed bed reactor, setting the fixed bed reactor to be in a preset working state, firstly introducing an ammonium sulfamate solution into the fixed bed reactor, after the ammonium sulfamate solution normally flows, then introducing diketene in the same direction, controlling the flow rate of the ammonium sulfamate solution and the diketene to ensure that the contact time of the ammonium sulfamate solution and the diketene is in a preset condition, and simultaneously, controlling a heat exchange device of the fixed bed reactor to ensure that the reaction temperature is also in the preset condition and the reaction time is up to the preset reaction time, thus finishing the reaction and obtaining the product acetoacetamide-N-triethylamine sulfonate solution. Due to the characteristics of the fixed bed reactor, the reaction can be continuously carried out, and the method is suitable for large-scale industrial production.

The method has the beneficial effects that the technical scheme that the traditional organic acid catalyst is combined with the reaction tank by combining the solid heteropoly acid catalyst with the fixed bed reactor instead of the traditional organic acid catalyst is adopted, so that on one hand, the post-treatment process of the product is simplified, the acesulfame honey product phase of the final product is better, and the use experience is obviously improved; on the other hand, the large-scale continuous production of the acetoacetamide-N-sulfonic acid triethylamine salt is realized, the reaction time is greatly shortened, the reaction yield is improved, and the production cost of the acesulfame is further reduced.

Type and amount of solid heteropolyacid catalyst

In the application, the type of the heteropoly acid catalyst is not limited, and all the solid heteropoly acid catalysts capable of providing acid sites can be used; in some embodiments herein, the solid heteropolyacid catalyst is a Keggin-type structured solid heteropolyacid catalyst, primarily a 1:12 series Keggin-type structure such as H₃[PMO₁₂O₁₄]·xH₂O, it has strong acidity and oxidizing property, its acidity is usually stronger than the acidity of the oxyacid making up each component of heteropoly acid, when used as oxidizing agent, it is very easy to oxidize other substances, make itself in reduction state and be very easy to regenerate, therefore, heteropoly acid catalyst can effectively catalyst amino sulfonic acid ammonium salt and diketene acylation reaction to go on smoothly on one hand, on the other hand, because its regeneration ability is strong, has obviously reduced the catalyst cost, further, has reduced the production cost of acesulfame-K.

In the present application, the amount of the solid heteropoly acid catalyst is not limited and can be determined according to the specification of the fixed bed reactor.

The dosage ratio of the sulfamic acid to the first methane chloride

In the amination step, the dosage ratio of sulfamic acid to first dichloromethane is not limited, and the sulfamic acid is completely dissolved; in some embodiments of the present application, the ratio of the molar amount of sulfamic acid to the molar amount of first dichloromethane is from 1:6 to 15, taking into account economic considerations.

The dissolving temperature of the sulfamic acid in the first methane chloride is 20-25 ℃, namely, the sulfamic acid can be dissolved at room temperature, if the temperature is lower than 20 ℃ or higher than 25 ℃, only a specific means is needed to realize, although the sulfamic acid can realize more rapid dissolution, higher economic cost is needed, and the sulfamic acid can be dissolved at room temperature because the sulfamic acid is not difficult to dissolve.

The dosage ratio of triethylamine to the second dichloromethane

In the method, in the amination step, the dosage ratio of triethylamine to the second dichloromethane is not limited, and the triethylamine is ensured to be completely dissolved; in some embodiments herein, the ratio of the molar amount of triethylamine to the molar amount of second dichloromethane in the amination step is 1:1.5 to 2.5, taking into account economic considerations.

The temperature of dissolving the triethylamine in the second dichloromethane can be set to be 10-20 ℃, and the heat dissipation in the dissolving process is facilitated under the low-temperature condition.

The dosage ratio of sulfamic acid to triethylamine

In the present application, the ratio of the amount of sulfamic acid to triethylamine in the amination step is not limited, and reference is made to the prior art, and in the present application, in order to increase the conversion of sulfamic acid, a slight excess of triethylamine may be used, and in some embodiments of the present application, the ratio of the mass amount of sulfamic acid to the mass amount of triethylamine is 1: 1-1.2.

Reaction temperature of amination reaction

The temperature of the amination reaction is not limited in this application, and since the amination reaction does not require heating nor cooling, it can be carried out at room temperature, and in some embodiments, can be 20-30 ℃.

The dosage ratio of the diketene to the third dichloromethane

In the application, in the acylation reaction step, the dosage ratio of the diketene to the third dichloromethane is not limited, and the diketene can be completely dissolved; in some embodiments of the present application, the ratio of the molar amount of diketene to the molar amount of the third dichloromethane is 1: 1.5-2.5.

The temperature of the diketene dissolved in the third dichloromethane can be set to be 10-20 ℃, and the heat dissipation in the dissolving process is facilitated under the low-temperature condition.

The dosage ratio of the sulfamic acid to the diketene

In the present application, in the above-mentioned method, the ratio of the amount of sulfamic acid to triethylamine in the amination step is not limited, and reference is made to the prior art, such as in chinese patent document CN112142687A, the molar ratio n (sulfamic acid) of sulfamic acid to diketene: n (diketene) ═ 1: 1.0-1.5.

In the prior art, diketene needs to be in large excess to obtain a relatively good technical effect, in the application, due to the combination of the solid heteropoly acid catalyst and the fixed bed reactor, the sulfamic acid and the diketene have larger contact area, a better mixing effect is obtained, and the upper limit of the dosage of the diketene relative to the prior art can be reduced, in some embodiments of the application, in the method, the ratio of the molar dosage of the sulfamic acid to the molar dosage of the diketene is 1:1-1.2, and in other embodiments 1: 1.02-1.1, thus achieving better technical effect.

Preset conditions

In the application, the preset conditions in the acylation reaction step are not limited, no danger occurs, and the reaction requirements of the ammonium sulfamate solution and the diketene can be met; in some embodiments herein, in the acylation step, the preset conditions are: setting the temperature to be 20-35 ℃; the reaction time was set to 10-120 s. That is, the acylation reaction step of this application is preferred to be carried out at lower temperature, because dichloromethane can take away a large amount of heat production, therefore, in this application, control by temperature change is relatively easy to realize, adopt any one among the prior art can, such as air condensation technique, circulating water condensation technique and heat exchange plate etc.. Due to the adoption of the method for combining the solid heteropoly acid catalyst and the fixed bed reactor, the reaction time of the acylation reaction step can be obviously shortened, and the reaction can be completed more thoroughly within 10-120 s. If the reaction temperature is lower than 20 ℃ and the reaction time is shorter than 10s, the reaction conditions are difficult to control, so that the reaction cost is high, the contact time of the raw materials is too short, and the reaction is incomplete; if the reaction temperature is higher than 35 ℃ and the reaction time is longer than 120s, the reaction temperature is too high, danger is easy to occur, the reaction time is too long, the time cost is increased, and other beneficial effects are not achieved; in other embodiments herein, in the acylation step, the predetermined conditions may preferably be: setting the temperature to be 25-30 ℃; the reaction time was set to 30-120 s.

Sources of drugs or reagents

In the present application, each drug or reagent may be prepared by a laboratory or a factory, or may be a commercially available product, which is not limited in the present application.

Example 1 (including example 1A, example 1B, example 1C, example 1D, example 1E)

Amination reaction step: 98kg of sulfamic acid and first dichloromethane were added in a molar ratio of 1:6, and controlling the dissolving temperature to be about 20-25 ℃ to obtain a dichloromethane solution of sulfamic acid, namely a first reaction solution. The dissolution can be in a continuous mixing apparatus or in a reaction vessel.

Adding triethylamine and second dichloromethane in a molar ratio of 1:1, and controlling the dissolving temperature to be 10-30 ℃ to obtain a second reaction solution, wherein the mass ratio of sulfamic acid to triethylamine is 1: 1-1.2. And gradually dropwise adding the second reaction solution into the reaction kettle in which the first reaction solution is positioned, mixing and stirring, controlling the temperature of the system to be 20-30 ℃, controlling the system to be alkalescent, and uniformly mixing to obtain the ammonium sulfamate solution.

Examples 1A, 1B, 1C, 1D, 1E all included an amination reaction step in which the mass ratio of sulfamic acid and triethylamine varied between the examples, as detailed in table 1.

And (3) acylation reaction: adding diketene and third dichloromethane in a molar ratio of 1:1.5, and controlling the dissolving temperature to be 10-20 ℃ to obtain a third reaction solution.

After the solid heteropoly acid catalyst is installed in the fixed bed reactor, the fixed bed reactor is started, and circulating water is adjusted to enable the circulating water to work normally.

And (3) introducing the ammonium sulfamate solution into a fixed bed reactor, introducing a third reaction solution and the ammonium sulfamate solution into the fixed bed reactor in the same direction after the ammonium sulfamate solution normally flows, and controlling the amount of the ammonium sulfamate solution and the third reaction solution to ensure that the molar ratio of the sulfamic acid to the diketene is 1: 1.02-1.1. After the reaction is started, the temperature of cooling water is reduced as much as possible, and the temperature of a reaction system is controlled to be 20-35 ℃; as catalyst performance degrades, the temperature may rise slightly within the control range.

The flow rates of the ammonium sulfamate salt solution and diketene were controlled so that the reaction time was controlled to be between 10 and 120 seconds. The obtained solution of the target product acetoacetamide-N-sulfonic acid triethylamine salt is subjected to conventional methods such as suction filtration, crystallization and the like to obtain a solid target product.

Examples 1A, 1B, 1C, 1D, 1E all included an acylation reaction step in which the molar ratio of sulfamic acid and diketene and the reaction conditions were varied from example to example, as detailed in table 1.

It should be noted that, the temperature values appearing in the above embodiments are only required to be controlled within the above temperature range because the reaction process is exothermic, and the application can be implemented without being precisely controlled within a certain temperature range, and the following embodiments are not described one by one.

Comparative example 1 (including comparative example 1A and comparative example 1B)

Amination reaction step: 98kg of sulfamic acid and triethylamine are mixed and stirred in a reaction kettle according to the mass ratio of 1:1, the system is controlled to be alkalescent, and ammonium sulfamate solution is obtained after uniform mixing.

Preparation of dichloromethane solution of diketene: diketene and dichloromethane were mixed in a molar ratio of 1: 8, and a solution of diketene in dichloromethane to form a third reaction solution.

And (3) acylation reaction: a fixed bed reactor was used, and no catalyst was used in this comparative example.

Introducing the ammonium sulfamate solution into a fixed bed reactor, controlling the flow rate of the ammonium sulfamate solution, introducing the third reaction liquid into the fixed bed reactor, and controlling the flow rate of the diketene; after the reaction is started, the temperature of the cooling water is adjusted to be as low as possible, and the temperature of the reaction system is controlled to be between 34 and 45 ℃. The obtained solution of the target product acetoacetamide-N-sulfonic acid triethylamine salt is subjected to conventional methods such as suction filtration, crystallization and the like to obtain a solid target product. The results of comparative example 1 are shown in table 1.

In comparative example 1, since a solution of diketene in methylene chloride was used, the flash point was increased and the safety was improved. The acylation reaction is exothermic reaction, after the reaction temperature is raised to 40 ℃, dichloromethane starts to vaporize, so that partial heat is taken away, the whole reaction time is obviously reduced compared with the reaction controlled below the flash point of diketene, the temperature is controlled by using dichloromethane vaporization, unreliable temperature control exists, and organic gas is not generated in the reaction of a closed system, so a large amount of harmful gas can be released, and the environment friendliness is poor.

As can be seen from table 1, in comparative example 1, the reaction requires longer reaction time to obtain higher yield, and longer reaction time and higher reaction temperature usually occur with more side reactions.

Comparative example 2 (comprising comparative example 2A, comparative example 2B, comparative example 2C, comparative example 2D and comparative example 2E)

Amination step, namely, mixing 98kg of sulfamic acid and first methane chloride in a molar ratio of 1: 15, controlling the dissolving temperature to be about 20-25 ℃, and obtaining a dichloromethane solution of sulfamic acid as a first reaction solution. The dissolution can be in a continuous mixing apparatus or in a reaction vessel. Triethylamine and dichloromethane were added in a molar ratio of 1: 1.2, and controlling the dissolving temperature to be 10-30 ℃ to obtain a second reaction solution, wherein the mass ratio of sulfamic acid to triethylamine is 1: 1-1.2. And gradually dropwise adding the second reaction solution into the reaction kettle in which the first reaction solution is positioned, mixing and stirring, and controlling the system to be alkalescent. And uniformly mixing to obtain the ammonium sulfamate solution.

Comparative example 2A, comparative example 2B, comparative example 2C, comparative example 2D and comparative example 2E each comprise an amination reaction step in which the mass ratio of sulfamic acid and triethylamine varies from example to example, see table 1 for details.

And (3) acylation reaction: a fixed bed reactor is used, but a solid heteropoly acid molecular sieve is not used.

Adding diketene and third dichloromethane in a molar ratio of 1: 2.0, and controlling the dissolving temperature to be 10-20 ℃ to obtain a third reaction solution.

Dropwise addition of the reaction mixture to an ammonium sulfamate solution as described with sulfamic acid: the molar ratio of acetic acid is 1: 0.05 calculated amount of acetic acid.

Introducing the ammonium sulfamate solution added with acetic acid into a fixed bed reactor, and controlling the flow rate of the ammonium sulfamate solution; introducing the third reaction liquid into the fixed bed reactor, and controlling the flow rate of the third reaction liquid; after the reaction is started, the temperature of the cooling water is reduced as much as possible, and the temperature of a reaction system is controlled to be between 20 and 35 ℃; as the activity of the zeolite molecular sieve decreases, the temperature increases slightly within the control range.

Controlling the amount of the ammonium sulfamate salt solution and the diketene according to the molar ratio of the sulfamic acid to the diketene in the ammonium sulfamate salt solution as 1:1-1.2 calculation; and controlling the reaction time of the ammonium sulfamate solution and the diketene to be between 10 and 120 seconds. The obtained solution of the target product acetoacetamide-N-sulfonic acid triethylamine salt is subjected to conventional methods such as suction filtration, crystallization and the like to obtain a solid target product. The results of comparative example 2 are shown in table 1. As can be seen from Table 1, under the conditions of comparative example 2, since the reaction temperature was low, the reaction time was short (within 120 s), the reaction was hardly progressed completely, the yield of the acetoacetamide-N-sulfonic acid triethylamine salt was very low, and more impurities were introduced.

TABLE 1

Note: the yield is calculated by the mass of the target product acetoacetamide-N-sulfonic acid triethylamine salt in the mass percent of the sulfamic acid.

As can be seen from table 1, the solid heteropoly acid molecular sieve in example 1 can complete the reaction rapidly in the fixed bed reactor, and the advantage of completing the reaction rapidly is that a relatively small amount of diketene can be added at a time to meet the requirement of subsequent production under the same productivity. From the reaction point of view, the whole reaction time is not suitable to be too long, and the maintenance time is longer, which will cause the reduction of the whole yield.

In addition, as can be seen from table 1, the yield of the reaction of example 1 is higher and the reaction speed is significantly increased compared to the reaction of comparative example 2 using acetic acid. The amount of triethylamine used in the reaction of example 1 shows that higher yields can be obtained without a slight excess of amine in the case of using a solid heteropolyacid catalyst in the present application. The method has the advantages of short reaction time, low requirement on equipment, suitability for industrial production, high overall product yield, approximate raw material molar ratio and less subsequent organic waste.

In summary, according to the technical scheme, the solid heteropoly acid catalyst is combined with the fixed bed reactor to replace the traditional organic acid catalyst combined reaction tank, so that on one hand, the product post-treatment process is simplified, the acesulfame honey product phase of the final product is better, and the use experience is obviously improved; on the other hand, the large-scale continuous production of the acetoacetamide-N-sulfonic acid triethylamine salt is realized, the reaction time is greatly shortened, the reaction yield is improved, and the production cost of the acesulfame is further reduced.

While the foregoing is directed to embodiments of the present application, other modifications and variations of the present application may be devised by those skilled in the art in light of the above teachings. It should be understood by those skilled in the art that the foregoing detailed description is for the purpose of better explaining the present application, and the scope of protection of the present application shall be subject to the scope of protection of the claims.

Furthermore, those skilled in the art will appreciate that while some embodiments described herein include some features included in other embodiments, rather than other features, combinations of features of different embodiments are meant to be within the scope of the application and form different embodiments. For example, in the following claims, any of the claimed embodiments may be used in any combination.