Acesulfame potassium composition and its method of manufacture

Abstract

To provide a composition and a method for producing high-purity acesulfame potassium.SOLUTION: A method for producing high-purity acesulfame potassium comprising: forming a cyclic sulfur trioxide adduct; hydrolyzing the cyclic sulfur trioxide adduct to form an acesulfame-H composition comprising acesulfame-H; neutralizing the acesulfame -H in the acesulfame-H composition to form a crude acesulfame potassium composition comprising acesulfame potassium less than 2800 wppm of acetoacetamide-N-sulfonic acid, wherein the neutralizing is conducted at a pH of 11.0 or less; and processing the crude acesulfame potassium composition to form a purified acesulfame potassium composition comprising acesulfame potassium and less than 37 wppm acetoacetamide-N-sulfonic acid.SELECTED DRAWING: None

Description

[Technical field]

[0001]

[0001] This application is related to and claims priority to U.S. Provisional Patent Application No. 62 / 397,484, filed September 21, 2016, and U.S. Provisional Patent Application No. 62 / 397,495, filed September 21, 2016, each of which is incorporated by reference in its entirety.

[0002]

[0002] The present invention relates generally to acesulfame potassium and to a method for producing acesulfame potassium, and more specifically to a method for producing high purity acesulfame potassium. [Background technology]

[0003]

[0003] Acesulfame potassium has a very strong sweet taste and is used as a sweetener in many food-related applications. In a conventional process for producing acesulfame potassium, sulfamic acid is reacted with an amine, e.g., triethylamine, to form an amidosulfamate, such as trialkylammonium amidosulfamate. The amidosulfamate is then reacted with diketene to form an acetoacetamide salt. The acetoacetamide salt can be cyclized, hydrolyzed, and neutralized to form acesulfame potassium. U.S. Patents 5,744,010 and 9,024,016 disclose representative processes for producing acesulfame potassium.

[0004]

[0004] Typically, the acetoacetamide salt intermediate is cyclized to form a cyclic sulfur trioxide adduct by reaction with sulfur trioxide in an inorganic or organic solvent. The solvent typically used in this reaction is an organic solvent such as a halogenated aliphatic hydrocarbon solvent, e.g., dichloromethane. The adduct formed by this reaction is subsequently hydrolyzed and then neutralized with potassium hydroxide to form potassium acesulfame.

[0005]

[0005] Acesulfame potassium products and intermediate compositions produced by conventional processes contain undesirable impurities such as acetoacetamido-N-sulfonic acid. Often limits on the content of various impurities are set by government regulations or customer guidelines. Separating many of these impurities using standard purification procedures such as evaporation, crystallization, and / or filtration has proven difficult, leading to consumer dissatisfaction and unsatisfied standards. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] U.S. Patent 5,744,010 [Patent Document 2] U.S. Patent 9,024,016 Summary of the Invention [Problem to be solved by the invention]

[0007]

[0006] There is a need for improved processes for producing high purity acesulfame potassium compositions which reduce or eliminate the formation of impurities such as acetoacetamido-N-sulfonic acid during the synthesis.

[0008]

[0007] All references discussed herein are incorporated herein by reference. [Means for solving the problem]

[0009]

[0008] The present application relates to a purified acesulfame potassium composition. The method for producing a cyclic sulfur trioxide composition comprising the steps of forming a cyclic sulfur trioxide adduct; The method includes hydrolyzing the sulfur trioxide adduct to form an acesulfame-H composition comprising acesulfame-H; neutralizing the acesulfame-H in the acesulfame-H composition to form a crude acesulfame potassium composition; and treating the crude acesulfame potassium composition to form a purified acesulfame potassium composition comprising acesulfame potassium and less than 37 wppm of acetoacetamido-N-sulfonic acid. The neutralization step is preferably carried out at or maintained at a pH of 11.0 or less. The crude acesulfame potassium composition may comprise acesulfame potassium and less than 2800 wppm of acetoacetamido-N-sulfonic acid. The neutralization step may include reacting acesulfame-H with a neutralizing agent, such as potassium hydroxide, in an acesulfame-H / neutralizing agent reaction mixture to form the acesulfame potassium composition. The potassium hydroxide may be produced by a membrane process and the purified acesulfame potassium composition may contain less than 10 wppm of mercury. In some cases, the acesulfame-H / neutralizing agent reaction mixture contains from 1% to 95% neutralizing agent and from 1% to 95% acesulfame-H by weight, based on the total weight of the acesulfame-H / neutralizing agent reaction mixture. The neutralizing step may include neutralizing the acesulfame-H in the acesulfame-H composition to form a crude acesulfame potassium composition further comprising acetoacetamide. In some embodiments, the crude acesulfame potassium composition contains from 500 wppm to 2375 wppm acetoacetamide-N-sulfonic acid and the purified acesulfame potassium composition contains less than 25 wppm acetoacetamide-N-sulfonic acid and further contains less than 25 wppm acetoacetamide. In one embodiment, the neutralization step is carried out or maintained at a pH in the range of 9.0 to 11.0, the crude acesulfame potassium composition contains from 20 wppm to 2500 wppm of acetoacetamide-N-sulfonic acid, and the purified acesulfame potassium composition contains less than 25 wppm of acetoacetamide-N-sulfonic acid and less than 15 wppm of acetoacetamide.In another embodiment, the neutralization step is carried out at or maintained at a pH in the range of 8 to 10.3, the crude acesulfame potassium composition comprises 600 wppm to 1200 wppm acetoacetamide-N-sulfonic acid, and the purified acesulfame potassium composition comprises less than 10 wppm acetoacetamide-N-sulfonic acid and less than 10 wppm acetoacetamide. In another embodiment, the neutralization step is carried out at or maintained at a pH in the range of 8 to 10.3, the crude acesulfame potassium composition comprises less than 2400 wppm acetoacetamide-N-sulfonic acid, and the purified acesulfame potassium composition comprises less than 10 wppm acetoacetamide-N-sulfonic acid and less than 10 wppm acetoacetamide. The purified acesulfame potassium composition may comprise less than 37 wppm acetoacetamide, e.g., less than 20 wppm acetoacetamide. The neutralization step may be carried out or maintained at a pH in the range of 9.0 to 11.0, and / or at a pH in the range of 9.0 to 10.5, e.g., 8.0 to 10.3, and / or at a temperature below 90° C. The treating step may include an evaporation step using a residence time of less than 180 minutes. Also disclosed is a method for producing a purified acesulfame potassium composition, comprising the steps of reacting sulfamic acid with triethylamine to form an amidosulfamate salt; reacting the amidosulfamate salt with diketene to form an acetoacetamide salt; contacting dichloromethane with sulfur trioxide to form a cyclization agent composition; reacting the acetoacetamide salt with sulfur trioxide in the cyclization agent composition to form a cyclic sulfur trioxide adduct; and hydrolyzing the cyclic sulfur trioxide adduct to form an acesulfame-H composition comprising acesulfame-H. neutralizing the acesulfame-H in the acesulfame-H to form a crude acesulfame potassium composition comprising acesulfame potassium and less than 2800 wppm acetoacetamide-N-sulfonic acid, wherein the neutralizing step is performed at or maintained at a pH of 11.0 or less; and treating the crude acesulfame potassium composition to form a purified acesulfame potassium composition comprising acesulfame potassium and less than 37 wppm acetoacetamide-N-sulfonic acid.Preferably, steps (a), (b), and (c) can be performed in any order before performing step (d). The neutralization step can be performed or maintained at a pH in the range of 9.0 to 11.0, and the crude acesulfame potassium composition can contain 20 wppm to 2500 wppm acetoacetamide-N-sulfonic acid, and the purified acesulfame potassium composition can contain less than 25 wppm acetoacetamide-N-sulfonic acid and less than 15 wppm acetoacetamide. The present application also describes crude, intermediate, and purified acesulfame potassium compositions produced by the methods described herein. In some cases, the present application describes acesulfame potassium compositions comprising acesulfame potassium, and less than 25 wppm acetoacetamide-N-sulfonic acid, and less than 25 wppm acetoacetamide. In some cases, the acesulfame potassium composition further comprises from 0.001 wppm to 5 wppm of organic impurities, and / or from 0.001 wppm to 5 wppm of at least one heavy metal, such as at least one heavy metal selected from the group consisting of mercury, lead, and mixtures thereof. In some cases, the acesulfame potassium composition further comprises mercury present in an amount from 1 wppb to 20 wppm, and / or lead present in an amount from 1 wppb to 25 wppm.

[0010]

[0009] In the following, the present invention will be described in detail with reference to the accompanying drawings. [Brief description of the drawings]

[0011] [Figure 1] FIG. 1 is a process flow sheet of a process for producing acesulfame potassium according to one embodiment of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] Introduction :

[0011] A conventional process for producing acesulfame potassium involves reacting sulfamic acid with an amine in the presence of acetic acid to form an amidosulfamate salt. The amidosulfamate salt is then reacted with an acetoacetylating agent, such as diketene, to form an acetoacetamide salt. The acetoacetamide salt is then reacted with a cyclizing agent, such as sulfur trioxide, to form a cyclic sulfur trioxide adduct. The cyclic sulfur trioxide adduct is then hydrolyzed and neutralized by conventional means to form a crude acesulfame potassium composition comprising acesulfame potassium. The composition is phase separated into an aqueous phase and an organic phase. The majority of the acesulfame potassium separates into the aqueous phase. As used herein, the term "crude acesulfame potassium composition" refers to the initial product of the neutralization step (without further purification) or the aqueous phase formed from the phase separation step. The crude acesulfame potassium composition comprises at least 5% by weight acesulfame potassium. Optionally, the crude acesulfame potassium composition may be processed to form an "intermediate acesulfame potassium composition" and / or a "purified acesulfame potassium composition," discussed below.

[0013]

[0012] Conventional acesulfame potassium compositions have been shown to contain several undesirable impurities, among them acetoacetamide and acetoacetamide salts, such as acetoacetamide-N-sulfonate triethylammonium salt. Acetoacetamide-N-sulfonic acid and its salts may also be present. The content limits for these compounds in the purified acesulfame potassium composition are often set by industry purity standards and / or standards established for the particular end product in which acesulfame potassium is used as a sweetener. In some cases, the limits for these impurities are set by government regulations. For most applications, high acesulfame potassium purity levels are preferred. Thus, crude acesulfame potassium compositions are usually treated by various processing operations to reduce the presence of these impurities. A non-limiting list of such processing operations includes evaporation, crystallization, and / or filtration.

[0014]

[0013] Without being bound by theory, it is believed that the hydrolyzed sulfur trioxide adduct It has been found that the addition of acesuifame potassium can cause stress, such as heat stress, on the acesulfame potassium molecule. This heat stress can also affect acesulfame-H (also known as sweetener acid), which is formed during the hydrolysis process and is a precursor to acesulfame potassium. This stress on acesulfame potassium and possibly acesulfame-H can cause the decomposition of these compounds, resulting in the formation of undesirable impurities. In some circumstances, this stress can cause the decomposition of acesulfame potassium / acesulfame-H into its forming reaction reactants, such as acetoacetamide and / or its salts and / or acetoacetamide-N-sulfonic acid, which can cause the formation of further impurities.

[0015]

[0014] It has also now been discovered that by employing certain reaction parameters, stress on acesulfame potassium (or acesulfame-H) can be advantageously reduced or eliminated, and / or decomposition of the product can be advantageously reduced or eliminated, thereby reducing or eliminating the formation of further impurities, ultimately resulting in a high purity final product.

[0016] In particular, it has now been discovered that by carrying out the neutralization step within specific pH ranges or limits, decomposition of acesulfame potassium (or acesulfame-H) and formation of impurities, including, for example, the formation of acetoacetamide-N-sulfamic acid and / or the (re)formation of acetoacetamide salts, is surprisingly reduced or eliminated. Traditionally, the neutralization step has been carried out at or maintained at very high pH levels to maximize the neutralization of acesulfame-H to acesulfame potassium and minimize the content of acesulfame-H in the resulting crude acesulfame potassium composition. The reduced decomposition of acesulfame potassium and acesulfame-H leads directly to the formation of a higher purity crude acesulfame potassium composition as discussed herein, which simplifies subsequent processing operations to form intermediate or purified acesulfame potassium compositions. The process also advantageously results in the formation of intermediate and purified compositions of acesulfame potassium having low acetoacetamide-N-sulfamic acid and / or acetoacetamide content.

[0017] In addition to the stresses formed during the neutralization step, the processing operations used to remove impurities from the acesulfame potassium in the crude acesulfame potassium composition may also result in stresses, such as heat stress, on the acesulfame potassium itself (or acesulfame-H), which may lead to decomposition. It is believed that under such stresses, acetoacetamide-N-sulfamic acid may decompose (and possibly hydrolyze) to acetoacetamide and N-sulfonic acid (and possibly N-sulfonic acid derivatives). Thus, heat stress during processing operations may lead to the formation of further undesirable by-products, such as acetoacetamide. Advantageously, by reducing the content of acetoacetamide-N-sulfamic acid in the crude acesulfame potassium composition, there is a concomitant reduction in the content of acetoacetamide which may be formed in further processing operations, thereby leading to improved efficiency and reduced acetoacetamide content in the final purified acesulfame potassium composition.

[0018]

[0017] Here, further specific terms used in this specification are defined. As used in this specification, "acetoacetamide" refers to the following molecule:

[0019] [ka]

[0020]

[0018] As used herein, "acetoacetamide-N-sulfonic acid" refers to the molecule shown below. In some cases, acetoacetamide-N-sulfonic acid may be a decomposition product of acesulfame potassium or acesulfame-H. As used herein, the term "acetoacetamide-N-sulfonic acid" also includes salts of acetoacetamide-N-sulfamic acid, such as potassium, sodium, and other alkali metal salts.

[0021] [ka]

[0022] The crude acesulfame composition may be processed to form an intermediate acesulfame potassium composition and a purified acesulfame composition, and the processing steps may include one or more concentration or separation operations.

[0023] "Intermediate acesulfame potassium composition" refers to a composition obtained by concentrating a crude acesulfame potassium composition, e.g., by removing water from the crude acesulfame potassium composition, the intermediate acesulfame potassium composition containing at least 10% by weight acesulfame potassium, based on the total weight of the intermediate acesulfame potassium composition, and having a higher weight percent of acesulfame potassium than that of the crude acesulfame potassium composition.

[0024] "Purified acesulfame potassium composition" refers to a composition obtained by separation, e.g., crystallization and / or filtration (preferably directly), of an intermediate acesulfame potassium composition. The purified acesulfame potassium composition contains at least 15% by weight acesulfame potassium, based on the total weight % of the purified acesulfame potassium composition, and has a higher weight % of acesulfame potassium than that of the intermediate acesulfame potassium composition.

[0025] As used herein, "residence time" refers to the time that a composition (or stream) being processed, e.g., a crude acesulfame potassium composition, is held during a particular processing operation. The residence time begins when the composition being processed is introduced into the processing operation, and the residence time ends when the resulting composition (formed by the processing) is discharged from the processing operation. As one particular example, the residence time for a concentration operation, e.g., evaporation, refers to the time that a crude acesulfame potassium composition is held during a particular processing operation. As another example, residence time for a separation operation, such as crystallization, refers to the time from when the crude acesulfame potassium composition is introduced into a crystallizer to when the intermediate acesulfame potassium composition is discharged from the crystallizer.

[0026] As used herein, "cyclization reaction time" refers to the time from the start of the acetoacetamide salt feed to the end of the acetoacetamide salt feed. In some cases, where indicated, the cyclization reaction time can include additional time after the end of the acetoacetamide salt feed, such as an additional 5 minutes or an additional 1 minute.

[0027]

[0024] The processing of a crude acesulfame potassium composition may involve one or more operations, such as a concentration operation and / or a separation operation. Generally, a concentration operation is not considered a separation operation. In some embodiments, one or more concentration operations and one or more separation operations comprise the overall processing of a crude acesulfame potassium composition, which results in a purified acesulfame potassium composition. In some cases, an overall concentration operation may include multiple individual concentration operations or units, and an overall separation operation may include multiple individual separation operations or units.

[0028] As used herein, "wppm" and "wppb" mean parts per million or parts per billion by weight, respectively, based on the total weight of the respective entire compositions, e.g., the total crude acesulfame potassium composition or the total purified acesulfame potassium composition.

[0029] Formation of acesulfame potassium (pH control) :

[0026] A method for producing a high purity acesulfame potassium composition is described herein. In one embodiment, the method includes the steps of forming a cyclic sulfur trioxide adduct, hydrolyzing the cyclic sulfur trioxide adduct to form an acesulfame-H composition comprising acesulfame-H, and neutralizing the acesulfame-H in the acesulfame-H composition (and optionally phase separating the neutralization reaction product) to form a crude acesulfame potassium composition. The crude acesulfame potassium composition contains acesulfame potassium and impurities, such as acetoacetamido-N-sulfonic acid, that are present in very low amounts, if at all.

[0030]

[0027] Other impurities may also be formed in the process steps described above. For example, the formation of a cyclic sulfur trioxide adduct may result in a cyclic sulfur trioxide adduct composition that includes the cyclic sulfur trioxide adduct and further reaction by-products and impurities. Similarly, the formation of acesulfame-H may result in an acesulfame-H composition that includes acesulfame-H and further reaction by-products and impurities.

[0031]

[0028] The formation of the cyclic sulfur trioxide adduct can include the steps of reacting sulfamic acid with triethylamine to form an amidosulfamate, reacting an amidosulfamate with diketene to form an acetoacetamide salt, contacting a solvent, such as dichloromethane, with a cyclizing agent, such as sulfur trioxide, to form a cyclizing agent composition, and reacting the acetoacetamide salt with sulfur trioxide in the cyclizing agent composition to form the cyclic sulfur trioxide adduct. The amidosulfamate-forming reaction, the acetoacetamide salt-forming reaction, and contacting the solvent with the cyclizing agent can be carried out in any order, so long as these steps are carried out before the reaction of the acetoacetamide salt with the cyclizing agent in the cyclizing agent composition.

[0032] As mentioned above, in the neutralization step, acesulfame-H is neutralized with a neutralizing agent to form acesulfame potassium. Importantly, the neutralization step is carried out at a low pH level. and / or the pH of the neutralization step is maintained at a low level, which reduces or eliminates the formation of some impurities in the crude acesulfame potassium composition, such as acetoacetamido-N-sulfonic acid. In this context, "conducting" means starting the neutralization step at a low pH level, and "maintaining" means that the step is conducted to ensure that the pH is maintained within the low pH range throughout the neutralization step.

[0033] In one embodiment, the neutralization step is carried out or maintained at a pH of 11.0 or less, e.g., 10.5 or less, 10 or less, 9.5 or less, 9.0 or less, 8.5 or less, 8.0 or less, 7.5 or less, 7.0 or less, or 6.5 or less. In some embodiments, the pH of the neutralization step is carried out or maintained at a value lower than the above mentioned limit values ​​(but not including the limit values ​​themselves). In terms of ranges, the neutralization step is preferably carried out or maintained at a pH in the range of 6.0 to 11.0, e.g., 7.0 to 11.0, 7.5 to 11.0, 9.0 to 11.0, 9 to 10.5, 7.0 to 10.5, 7.0 to 10.0, 8 to 10.5, 8 to 10.3, 8 to 10, or 7.5 to 9.0. The pH of the neutralization step is preferably performed or maintained within the ranges stated above (end points not included).

[0034] In a preferred embodiment, the neutralization step involves reacting the acesulfame-H in the acesulfame-H composition with a neutralizing agent to form the acesulfame potassium composition.

[0032] The use of these pH ranges and limits provides excellent conversion of acesulfame-H to acesulfame potassium while minimizing the content of acesulfame-H and acesulfame potassium decomposition products in the resulting crude acesulfame potassium composition (and purified acesulfame potassium composition). Although low pH levels are generally desirable in accordance with some aspects of the present invention, it has now been discovered that an excessively low pH in the neutralization step can undesirably reduce the conversion of acesulfame-H to acesulfame potassium. An excessively high pH in the neutralization step can result in the decomposition of acesulfame potassium into undesired by-products. Acesulfame-H is known to be less stable than acesulfame potassium and therefore more susceptible to decomposition. The use of the above pH ranges and limits ensures the formation of acesulfame potassium while fewer acesulfame-H molecules decompose into their precursors, such as acetoacetamide. In addition to reduced levels of acetoacetamide-N-sulfonic acid in the crude acesulfame potassium composition, the lower pH level may also have a beneficial effect on other impurities that may be formed downstream of the neutralization step. For example, reducing the acetoacetamide-N-sulfonic acid content also reduces the formation of its decomposition by-products during the evaporation and / or crystallization steps.

[0035]

[0033] The neutralizing agent preferably comprises a potassium-containing compound. Preferably, the neutralizing agent comprises potassium hydroxide. Other suitable examples of neutralizing agents include KHCO3, K2CO3, and potassium alcoholates. In a preferred embodiment, the neutralizing agent comprises a base, such as a hydroxide compound. When potassium hydroxide is used, it can be produced by a membrane process. Alternatively, it can be produced by an amalgam process.

[0036] The specific method used to maintain the pH in the neutralization step within the desired range can vary widely. In some embodiments, the pH in the neutralization step is effected or maintained within the desired range by controlling the amount of neutralizing agent, preferably a basic compound, such as a hydroxide, used in the neutralization step. In one embodiment, if a continuous process is used, the pH of the neutralization step is the pH at which the continuous process is maintained. In one embodiment, if a batch process is used, the pH of the neutralization step is the final pH of the neutralization reaction mixture, e.g., the pH at the end of the batch operation.

[0037] In some cases, the pH during the neutralization step can be maintained within a desired range by manipulating the components of the neutralization reaction mixture, including acesulfame-H and the neutralizing agent (and even the solvent). For example, the composition of the neutralization reaction mixture can include 1% to 95% by weight, e.g., 10% to 85% by weight, or 25% to 75% by weight, of the neutralizing agent; and 1% to 95% by weight, e.g., 10% to 85% by weight, or 25% to 75% by weight, of the acesulfame-H. These concentration ranges are based on the mixture of the neutralizing agent and acesulfame-H (without the solvent).

[0038] In some embodiments, the temperature at which the crude acesulfame potassium composition is treated is maintained at a low level. Also, in some embodiments, the residence time (of the crude acesulfame potassium composition or its derivatives) in one or more operations of the treatment process is maintained at a low level. By using treatment under these parameters, the decomposition of acetoacetamido-N-sulfonic acid to other impurities is advantageously reduced / eliminated.

[0039] In some embodiments, the processing of the crude acesulfame potassium composition, e.g., one or more of the steps constituting the processing operation, is carried out at or maintained at a low temperature. Preferably, the processing operation includes a concentration operation and a separation operation, which are carried out at a low temperature.

[0040] In some embodiments, the concentration operation, e.g., one or more of the steps that make up the concentration operation, is carried out at or maintained at a low temperature, e.g., below 90° C., e.g., below 88° C., below 85° C., below 83° C., below 80° C., below 78° C., below 75° C., below 73° C., below 70° C., below 65° C., below 55° C., below 50° C., or below 46° C. In some cases, the temperature of the concentration operation can be maintained above 0° C., e.g., above 10° C., above 15° C., above 20° C., above 22° C., above 25° C., above 35° C., above 40° C., or above 50° C. In terms of ranges, the temperature of the concentration operation may be in the range of 0°C to 90°C, for example, 25°C to 90°C, 55°C to 90°C, 10°C to 88°C, 10°C to 85°C, 75°C to 88°C, 80°C to 88°C, 15°C to 85°C, 75°C to 85°C, 20°C to 83°C, 20°C to 80°C, 22°C to 78°C, 25°C to 75°C, 25°C to 73°C, 15°C to 50°C, 25°C to 65°C, 22°C to 50°C, 20°C to 55°C, 25°C to 70°C, or 30°C to 60°C.

[0041] In some embodiments, the separation operation, e.g., one or more of the steps that make up the separation operation, is carried out at or maintained at a low temperature, e.g., below 35° C., below 30° C., below 25° C., below 20° C., below 15° C., below 10° C., below 8° C., below 6° C., below 5° C., or below 0° C. In some cases, the temperature of the separation operation can be maintained above −25° C., e.g., above −10° C., above 0° C., above 5° C., above 10° C., above 15° C., above 25° C., or above 30° C. In terms of ranges, the temperature of the separation operation may range from −25° C. to 35° C., e.g., −10° C. to 35° C., 0° C. to 35° C., 5° C. to 30° C., −10° C. to 30° C., −10° C. to 25° C., −10° C. to 20° C., −10° C. to 15° C., 0° C. to 25° C., or −10° C. to 30° C. Using the above temperatures in the process advantageously improves the final product purity.

[0042] In some embodiments, the processing of the crude acesulfame potassium composition, e.g., one or more of the steps constituting the processing operation, is carried out at or maintained at a short residence time. Preferably, the processing operation includes a concentration operation and a separation operation, which are carried out at a short residence time and / or at a low pH.

[0043] In some embodiments, the concentration operation, e.g., one or more of the steps that make up the concentration operation, is performed or maintained at a short residence time. In one embodiment, the residence time is less than 180 minutes, e.g., less than 170 minutes, less than 150 minutes, less than 120 minutes, less than 100 minutes, less than 90 minutes, less than 75 minutes, less than 50 minutes, less than 40 minutes, less than 30 minutes, less than 20 minutes, or less than 10 minutes. In terms of the lower limit, the residence time may be at least 1 second, e.g., at least 10 seconds, at least 1 minute, at least 10 minutes, or at least 15 minutes. In terms of ranges, the residence time may range from 1 second to 180 minutes, e.g., 10 seconds to 180 minutes, 1 minute to 180 minutes, 10 minutes to 150 minutes, 1 minute to 50 minutes, 1 minute to 30 minutes, 10 minutes to 100 minutes, 1 minute to 80 minutes, 10 minutes to 80 minutes, 10 minutes to 50 minutes, 15 minutes to 90 minutes, or 15 minutes to 75 minutes. The same residence time limits and ranges can be applied to a separation operation, e.g., one or more of the steps that make up a separation operation. The use of residence times in the concentration operation and / or separation operation advantageously improves final product purity.

[0044] In some embodiments, the concentration operation, e.g., one or more of the steps constituting the concentration operation, is carried out at or maintained at a low pH. In one embodiment, the pH of the separation is maintained below 10.0, e.g., below 9.5, below 9.0, below 8.5, below 8.0, below 7.5, below 7.0, or below 6.5. In terms of ranges, the pH of the concentration operation is preferably maintained between 6.0 and 10.0, e.g., between 6.5 and 9.5, between 7.0 and 9.0, or between 7.5 and 8.5. The same pH limits and ranges can be applied to the separation operation, e.g., one or more of the steps constituting the separation operation. By using low pH levels in the concentration operation or separation operation, the final product purity is advantageously improved. The purified acesulfame potassium compositions formed by one or more of the processes described herein have a high degree of purity.

[0045] Acesulfame potassium composition :

[0044] The crude acesulfame potassium composition is formed by hydrolyzing a cyclic sulfur trioxide adduct to form an acesulfame-H composition, as discussed herein, and neutralizing the acesulfame-H in the acesulfame-H composition to form a crude acesulfame potassium composition. The product of the neutralization step is phase separated into an aqueous phase and an organic phase. The crude acesulfame potassium composition can be obtained (without further purification) from the aqueous phase. The crude acesulfame potassium composition includes acesulfame potassium and acetoacetamide-N-sulfonic acid, e.g., less than 2800 wppm, e.g., less than 2700 wppm, less than 2600 wppm, less than 2500 wppm, less than 2400 wppm, less than 2000 wppm, less than 1500 wppm, less than 1000 wppm, less than 500 wppm, or less than 100 wppm of acetoacetamide-N-sulfonic acid. In terms of ranges, the crude acesulfame potassium composition can contain from 1 wppm to 2800 wppm, e.g., from 1 wppm to 2700 wppm, from 10 wppm to 2700 wppm, from 20 wppm to 2500 wppm, from 100 wppm to 2500 wppm, from 500 wppm to 2500 wppm, from 1500 to 2400 wppm, from 500 wppm to 2375 wppm, from 600 wppm to 2000 wppm, from 900 to 1900 wppm, from 300 wppm to 1500 wppm, from 400 wppm to 1400 wppm, from 600 wppm to 1200 wppm, or from 700 wppm to 1100 wppm of acetoacetamido-N-sulfonic acid.

[0046] The crude acesulfame potassium composition may further comprise acetoacetamide, which may be present in the amounts discussed above with respect to acetoacetamide-N-sulfonic acid.

[0046] A purified acesulfame potassium composition, which is typically suitable for end-user use, is formed by treating the crude acesulfame potassium composition to remove impurities. In some cases, the purified acesulfame potassium composition is typically the product that is sold. The purified acesulfame potassium composition preferably contains acesulfame potassium and less than 37 wppm, e.g., less than 35 wppm, less than 30 wppm, less than 25 wppm, less than 20 wppm, less than 15 wppm, less than 12 wppm, less than 10 wppm, less than 7 wppm, less than 5 wppm, less than 3 wppm, less than 1 wppm, less than 0.8 wppm, less than 0.5 wppm, less than 1 wppm, less than 0.8 wppm, less than 0.5 wppm, less than 0.8 ... The acesulfame potassium composition may contain less than 0.5 wppm, or less than 0.3 wppm of acetoacetamide. In some cases, the purified acesulfame potassium composition is free of acetoacetamide, e.g., substantially free (undetectable) of acetoacetamide. In terms of ranges, the purified acesulfame potassium composition may contain from 1 wppb to 37 wppm, e.g., from 10 wppb to 35 wppm, from 10 wppb to 25 wppm, from 10 wppb to 15 wppm, from 10 wppb to 12 wppm, from 10 wppb to 10 wppm, from 10 wppb to 7 wppm, from 10 wppb to 5 wppm, from 10 wppb to 3 wppm, from 100 wppb to 15 wppm, from 100 wppb to 10 wppm, or from 100 wppb to 5 wppm of acetoacetamide.

[0047] The purified acesulfame potassium composition preferably comprises a mixture of acesulfame potassium and less than 37 wppm, e.g., less than 35 wppm, less than 30 wppm, less than 25 wppm, less than 20 wppm, less than 15 wppm, less than 12 wppm, less than 10 wppm, less than 7 wppm, less than 5 wppm, less than 3 wppm, less than 1 wppm, less than 0.8 wppm, less than 0.5 wppm, or less than 0.3 wppm of acetoacetamide-N-sulfonic acid. In some cases, the purified acesulfame potassium composition is free of acetoacetamide-N-sulfonic acid, e.g., substantially free (undetectable) of acetoacetamide-N-sulfonic acid. In terms of ranges, the purified acesulfame potassium composition can contain from 1 wppb to 37 wppm, e.g., from 10 wppb to 35 wppm, from 10 wppb to 25 wppm, from 10 wppb to 15 wppm, from 10 wppb to 12 wppm, from 10 wppb to 10 wppm, from 10 wppb to 7 wppm, from 10 wppb to 5 wppm, from 10 wppb to 3 wppm, from 100 wppb to 15 wppm, from 100 wppb to 10 wppm, or from 100 wppb to 5 wppm of acetoacetamido-N-sulfonic acid.

[0048]

[0048] The content of acetoacetamide-N-sulfonic acid and / or acetoacetamide in the crude, intermediate or purified acesulfame potassium composition can be measured by high performance liquid chromatography (HPLC) analysis according to the European Pharmacopoeia guidelines for thin layer chromatography (2017) (compatible with HPLC). A specific measurement method uses a Shimadzu LC Systems HPLC unit with a CBM-20 Shimadzu controller and equipped with an IonPac NS1 ((5 μm) 150×4 mm) analytical column and an IonPac NG1 guard column (35×4.0 mm). For detection (at wavelengths of 270 nm and 280 nm), a Shimadzu SPD-M20A photodiode array detector can be used. The analysis can be performed at a column temperature of 23° C. As the first eluent, an aqueous mixture of tetrabutylammonium hydrogen sulfate (3.4 g / L), acetonitrile (300 mL / L), and potassium hydroxide (0.89 g / L) can be used; as the second eluent, an aqueous mixture of tetrabutylammonium hydrogen sulfate (3.4 g / L) and potassium hydroxide (0.89 g / L) can be used. Elution can be performed in gradient mode according to the following second eluent flow profile:

[0049] · 0–3 min: constant at 80% (v / v); 3-6 min: Linear decrease to 50% (v / v); · 6–15 min: constant at 50% (v / v); 15-18 minutes: Linear decrease to 0%; 18-22 min: constant at 0%; 22–24 min: linear increase to 80% (v / v); 24~35 min: constant at 80% (v / v). The total flow rate of the eluent may be about 1.2 mL / min. Data collection and calculations may be performed using Shimadzu's LabSolution software.

[0050] As described above, the crude acesulfame potassium composition is obtained by the above-mentioned reactions, hydrolysis, and neutralization, and a purified acesulfame potassium composition is formed by processing the crude acesulfame potassium composition. In a preferred embodiment, the neutralization is performed at or near a pH of 11.0 or less, e.g., 10.5 or less, 10 or less, 9.5 or less, 9.0 or less, 8.5 or less, 8.0 or less, 7.5 or less, 7.0 or less, or 6.5 or less (optionally a pH in the range of 7.5 to 11, e.g., 9.0 to 11.0, 9 to 10.5, 7.0 to 10.5, 7.0 to 10.0, 8 to 10.5, 8 to 10.3, 8 to 10, or 7.5 to 9.0). the crude acesulfame potassium composition may have less than 2800 wppm, e.g., less than 2700 wppm, less than 2600 wppm, less than 2500 wppm, less than 2400 wppm, less than 2000 wppm, less than 1500 wppm, less than 1000 wppm, less than 500 wppm, or less than 100 wppm acetoacetamido-N-sulfonic acid (in some cases, from 1 wppm to 2800 wppm, e.g., from 1 wppm to 2800wppm, 10wppm~2700wppm, 20wppm~2500wppm, 100wppm~2500wppm, 500wppm~2500wppm, 1500~2400wppm, 500wppm pm~2375wppm, 600wppm~2000wppm, 900~1900wppm, 300wppm~1500wppm, 400wppm~1400wppm, 600wppm~1200wppm, and the purified acesulfame potassium composition may contain between 700 wppm and 1100 wppm of acetoacetamide-N-sulfonic acid; the purified acesulfame potassium composition may contain less than 37 wppm, e.g., less than 35 wppm, less than 30 wppm, less than 25 wppm, less than 20 wppm, less than 15 wppm, less than 12 wppm, less than 10 wppm, less than 7 wppm, less than 5 wppm, less than 3 wppm, less than 1 wppm, less than 0.8 wppm, less than 0.5 wppm, or less than 0.less than 3 wppm acetoacetamide-N-sulfonic acid (optionally between 1 wppb and 37 wppm, e.g. between 10 wppb and 35 wppm, between 10 wppb and 25 wppm, between 10 wppb and 15 wppm, between 10 wppb and 12 wppm, between 10 wppb and 10 wppm, between 10 wppb and 7 wppm, between 10 wppb and 5 wppm, between 10 wppb and 3 wppm, between 100 wppb and 15 wppm, between 100 wppb and 10 wppm, or between 100 wppb and 5 wppm of acetoacetamide-N-sulfonic acid); and less than 37 wppm, e.g. less than 35 wppm, less than 30 wppm, less than 25 wppm, less than 20 wppm, less than 15 wppm pm, less than 12 wppm, less than 10 wppm, less than 7 wppm, less than 5 wppm, less than 3 wppm, less than 1 wppm, less than 0.8 wppm, less than 0.5 wppm, or less than 0.3 wppm acetoacetamide (in some cases, 10 wppb to 37 wppm, e.g., 10 wppb to 35 wppm, 10 wppb to 15 wppm, 10 wppb to 12 wppm, 10 wppb to 10 wppm, 10 wppb to 7 wppm, 10 wppb to 5 wppm, 10 wppb to 3 wppm, 100 wppb to 15 wppm, 100 wppb to 10 wppm, or 100 wppb to 5 wppm acetoacetamide).

[0051] In certain embodiments, the crude acesulfame potassium composition contains from 500 wppm to 2375 wppm of acetoacetamide-N-sulfonic acid and the purified acesulfame potassium composition contains less than 25 wppm of acetoacetamide-N-sulfonic acid and further contains less than 25 wppm of acetoacetamide.

[0052] In another particular embodiment, the neutralization is effected at or maintained at a pH in the range of 9.0 to 11.0, the crude acesulfame potassium composition contains from 20 wppm to 2500 wppm of acetoacetamide-N-sulfonic acid, and the purified acesulfame potassium composition contains less than 25 wppm of acetoacetamide-N-sulfonic acid and less than 15 wppm of acetoacetamide.

[0053] In another particular embodiment, the neutralization is carried out at or maintained at a pH in the range of 8.0 to 10.3, the crude acesulfame potassium composition contains 600 wppm to 1200 wppm of acetoacetamido-N-sulfonic acid, and the purified acesulfame potassium composition contains 600 wppm to 1200 wppm of acetoacetamido-N-sulfonic acid. contains less than 10 wppm acetoacetamide-N-sulfonic acid and less than 10 wppm acetoacetamide.

[0054] In another particular embodiment, neutralization is effected or maintained at a pH in the range of 8 to 10.3, and the crude acesulfame potassium composition contains less than 2400 wppm acetoacetamide-N-sulfonic acid and the purified acesulfame potassium composition contains less than 10 wppm acetoacetamide-N-sulfonic acid and less than 10 wppm acetoacetamide.

[0055] In another particular embodiment, neutralization is effected at or maintained at a pH in the range of 9.0 to 11.0, the crude acesulfame potassium composition contains from 500 wppm to 2375 wppm of acetoacetamide-N-sulfonic acid and the purified acesulfame potassium composition contains from 10 wppb to 10 wppm of acetoacetamide-N-sulfonic acid and from 10 wppb to 10 wppm of acetoacetamide.

[0056]

[0055] The acesulfame potassium compositions (crude and / or purified compositions) may in some cases contain other impurities. Representative impurities include halo-acesulfame potassium, among others. The acesulfame potassium compositions (crude and / or purified compositions) may also contain heavy metals. The organic impurities and / or heavy metals may be present in an amount ranging from 1 wppb to 25 wppm, e.g., 100 wppb to 20 wppm, 100 wppb to 15 wppm, 500 wppb to 10 wppm, or 1 wppm to 5 wppm, based on the total weight of the respective acesulfame potassium composition (crude or purified composition). Heavy metals have a relatively high density, e.g., 3 g / cm 3 Higher or 7g / cm 3Heavy metals are defined as metals having a higher density than lead. Exemplary heavy metals include lead and mercury. In some cases, the crude or refined acesulfame potassium composition may contain mercury in an amount ranging from 1 wppb to 25 wppm, e.g., 100 wppb to 20 wppm, 100 wppb to 15 wppm, 500 wppb to 10 wppm, or 1 wppm to 5 wppm. In terms of limits, the crude or refined acesulfame potassium composition may contain less than 25 wppm, e.g., less than 20 wppm, less than 15 wppm, less than 10 wppm, or less than 5 wppm of mercury. In some cases, the crude or refined acesulfame potassium composition may contain lead in an amount ranging from 1 wppb to 25 wppm, e.g., 100 wppb to 20 wppm, 100 wppb to 15 wppm, 500 wppb to 10 wppm, or 1 wppm to 5 wppm. In terms of limits, a crude or purified acesulfame potassium composition may contain less than 25 wppm lead, e.g., less than 20 wppm, less than 15 wppm, less than 10 wppm, or less than 5 wppm. In some cases, when potassium hydroxide is formed by a membrane process, the resulting crude or purified acesulfame potassium composition may have very low levels of mercury, if any, e.g., less than 10 wppm, less than 5 wppm, less than 3 wppm, less than 1 wppm, less than 500 wppb, or less than 100 wppb.

[0057] Intermediate reaction parameters : The reaction for producing high purity acesulfame potassium is described in more detail below.

[0058] Amidosulfamate formation reaction :

[0057] In the first reaction step, sulfamic acid is reacted with an amine to form a sulfamate. A representative reaction scheme for producing triethylammonium sulfamate using triethylamine as the amine is shown in reaction (1) below.

[0059] [ka]

[0060] Also present in the first reaction mixture is acetic acid, which reacts with an amine, such as triethylamine, to form triethylammonium acetate, as shown in reaction (2) below.

[0061] [ka]

[0062] The amines used in these reactions may vary widely. Preferably, the amine comprises triethylamine. In one embodiment, the amine is selected from the group consisting of trimethylamine, diethylpropylamine, tri-n-propylamine, triisopropylamine, ethyldiisopropylamine, tri-n-butylamine, triisobutylamine, tricyclohexylamine, ethyldicyclohexylamine, N,N-dimethylaniline, N,N-diethylaniline, benzyldimethylamine, pyridine, substituted pyridines such as picoline, lutidine, collidine, or methylethylpyridine, N-methylpiperidine, N-ethylpiperidine, N-methylmorpholine, N,N-dimethylpiperazine, 1,5-diazabicyclo[4.3.0]-non-5-ene, 1,8-diaza The amine may be selected from the group consisting of bicyclo[5.4.0]-undec-7-ene, 1,4-diazabicyclooctane, tetramethylhexamethylenediamine, tetramethylethylenediamine, tetramethylpropylenediamine, tetramethylbutylenediamine, 1,2-dimorpholylethane, pentamethyldiethyltriamine, pentaethyldiethylenetriamine, pentamethyldipropylenetriamine, tetramethyldiaminomethane, tetrapropyldiaminomethane, hexamethyltriethylenetetramine, hexamethyltripropylenetetramine, diisobutylenetriamine, triisopropylenetriamine, and mixtures thereof.

[0063] Acetoacetamide salt formation reaction : Once formed in reaction (1), the sulfamate salt is reacted with an acetoacetylating agent to form an acetoacetamide salt, preferably an acetoacetamide-N-sulfonate triethylammonium salt. Preferably, the acetoacetylating agent comprises diketene, although other acetoacetylating agents can be used with or without diketene.

[0064] In one embodiment, the resulting acetoacetamide salt corresponds to formula (3):

[0065] [ka]

[0066] In the formula, M + is a suitable ion. Preferably, M + is an alkali metal ion or N + R1R2R3R4. R1, R2, R3, and R4 are each independently an organic group or hydrogen, preferably H, or C1-C8 alkyl, C6-C 10 It may be cycloalkyl, aryl, and / or aralkyl. In a preferred embodiment, R is hydrogen and R 2, R3, and R4 are alkyl, for example ethyl.

[0067] A representative reaction scheme for forming an acetoacetamide salt uses trialkylammonium amidosulfamate and diketene as reactants to produce acetoacetamide triethylammonium salt as shown below in reaction (4).

[0068] [ka]

[0069] In one embodiment, the reaction is carried out in the presence of a catalyst, which may vary widely. In some embodiments, the catalyst comprises one or more amines and / or phosphines. Preferably, the catalyst comprises triethylamine. In some cases, trimethylamine serves as both the catalyst and the reactant.

[0070] In one embodiment in which the amidosulfamate-forming reaction and the acetoacetamide salt-forming reaction are carried out in separate reactors, the second reaction mixture includes amidosulfamate, diketene, and a catalyst, such as triethylamine. Preferably, the catalyst is carried over from the first reaction to the reaction mixture of the second reaction. The second reaction mixture is then subjected to conditions effective to form the acetoacetamide salt.

[0071] In one embodiment, the composition of the second reaction mixture may be similar to the composition of the first reaction mixture. In a preferred embodiment, the reaction product of the amidosulfamate-forming reaction provides the amidosulfamate component of the second reaction mixture. In addition to the components described above, the second reaction mixture may further include reaction by-products from the first reaction, or unreacted starting materials.

[0072] In one embodiment, the amount of acetoacetylating agent, e.g., diketene, should be at least equimolar to the reactant amidosulfamate provided. In one embodiment, the process can use less than a 30 mole % excess of diketene, e.g., less than a 10 mole % excess. Larger excesses are also contemplated.

[0073] The amidosulfamate-forming reaction and / or the acetoacetamide salt-forming reaction can use an organic solvent. Suitable inert organic solvents include any organic solvent that does not react in an undesirable manner with the starting material, cyclization agent, final product, and / or catalyst in the reaction. The solvent preferably has the ability to at least partially dissolve the amidosulfamate. Representative organic solvents include halogenated aliphatic hydrocarbons, preferably having 4 or fewer carbon atoms, such as methylene chloride, chloroform, 1,2-dichloroethane, trichloroethylene, tetrachloroethylene, trichlorofluoroethylene; aliphatic ketones, preferably having 3 to 6 carbon atoms, such as acetone, methyl ethyl ketone; aliphatic ethers, preferably cyclic aliphatic ethers having 4 or 5 carbon atoms, such as tetrahydrofuran, dioxane; lower aliphatic carboxylic acids, preferably having 2 to 6 carbon atoms, such as acetic acid, propionic acid; aliphatic nitriles, preferably acetonitrile; N-alkyl substituted amides of carbonic acid and lower aliphatic carboxylic acids, preferably having 5 or fewer carbon atoms, such as tetramethylurea, dimethylformamide, dimethylacetamide, N-methylpyrrolidone; aliphatic sulfoxides, preferably dimethylsulfoxide, and aliphatic sulfones, preferably sulfolane.

[0074] Particularly preferred solvents include dichloromethane (methylene chloride), 1,2-dichloroethane, acetone, glacial acetic acid, and dimethylformamide, with dichloromethane (methylene chloride) being particularly preferred. The solvents may be used either alone or in mixtures. In one embodiment, the solvent is a halogenated aliphatic hydrocarbon solvent, preferably the solvent is dichloromethane. Chloroform and tetrachloromethane are also representative solvents.

[0075] In one embodiment, the acetoacetamide salt forming reaction is carried out at a temperature ranging from -30°C to 50°C, for example, from 0°C to 25°C. The reaction pressure can vary widely. In a preferred embodiment, the reaction is carried out at atmospheric pressure, although other pressures are contemplated. The reaction time can vary widely, preferably from 0.5 hours to 12 hours, for example, from 1 hour to 10 hours. In one embodiment, the reaction is carried out by introducing the amidosulfamate and metering in the diketene. In another embodiment, the reaction is carried out by introducing the diketene and metering in the amidosulfamate. The reaction can be carried out by introducing the diketene and amidosulfamic acid and metering in the catalyst.

[0076] Once formed, each reaction product is optionally subjected to one or more purification steps. For example, the solvent can be separated from the reaction product, for example by distillation, and the residue (mainly acetoacetamide-N-sulfonate) can be recrystallized from a suitable solvent, such as, for example, acetone, methyl acetate, or ethanol.

[0077] Cyclization and Hydrolysis : The acetoacetamide salt is reacted with a cyclizing agent, such as a cyclizing agent in a cyclizing agent composition, in the presence of a solvent to form a cyclic sulfur trioxide adduct, and in some cases a cyclic (sulfur trioxide) adduct composition containing impurities. In some cases, a cooling step is performed prior to the cyclic sulfur trioxide adduct forming reaction. In one embodiment, the cyclization is performed by using at least an equimolar amount of the cyclizing agent. The cyclizing agent can be dissolved in an inert inorganic or organic solvent. The cyclizing agent is generally used in molar excess, such as up to a 20-fold excess, or up to a 10-fold excess based on the total moles of the acetoacetamide salt. A representative cyclization reaction using sulfur trioxide as the cyclizing agent is shown below in reaction (5).

[0078] [ka]

[0079] In one embodiment, the weight ratio of solvent to cyclizing agent in the cyclizing agent composition is at least 1:1, such as at least 2:1, or at least 5:1. In one embodiment, the weight ratio of solvent to cyclizing agent in the cyclizing agent composition is in the range of 1:1 to 25:1, such as 1:1 to 10:1, 2:1 to 10:1, or 5:1 to 10:1.

[0080] The cyclizing agent may be any compound that will initiate ring closure of the acetoacetamide salt. Sulfur trioxide is the preferred cyclizing agent, although other cyclizing agents are contemplated. The cyclization agent can be added to the reaction mixture either in solid or liquid form, or by condensation in the vapor. Suitable inert inorganic or organic solvents are those liquids that do not react in an undesirable manner with sulfur trioxide or with the starting materials or end products of the reaction. Preferred organic solvents include, but are not limited to, halogenated aliphatic hydrocarbons, preferably having 4 or fewer carbon atoms, such as methylene chloride (dichloromethane), chloroform, 1,2-dichloroethane, trichloroethylene, tetrachloroethylene, trichlorofluoroethylene; esters of carbonic acid with lower aliphatic alcohols, preferably methanol or ethanol; nitroalkanes, preferably having 4 or fewer carbon atoms, especially nitromethane; alkyl-substituted pyridines, preferably collidine; and aliphatic sulfones, preferably sulfolane. Particularly preferred solvents for the cyclization reaction include dichloromethane (methylene chloride), 1,2-dichloroethane, acetone, glacial acetic acid, and dimethylformamide, with dichloromethane (methylene dichloride) being particularly preferred. Other solvents, such as those mentioned herein, may also be suitable as solvents. The solvents can be used either alone or in mixtures. In one embodiment, the solvent is a halogenated aliphatic hydrocarbon solvent, preferably the solvent is dichloromethane. The process can use these solvents alone or in mixtures thereof.

[0081] In some cases, the solvent in the cyclizing agent composition can be selected from (1) concentrated sulfuric acid, (2) liquid sulfur dioxide, or (3) an inert organic solvent. In a preferred embodiment, the same solvent is used in both the acetoacetamide salt-forming reaction and the cyclization reaction. One advantage is that the solution obtained in the acetoacetamide salt-forming reaction can be used immediately in the cyclization without isolating the acetoacetamide salt-forming reaction product.

[0082] In one embodiment, the reaction temperature for the cyclization reaction is in the range of −70° C. to 175° C., for example, −40° C. to 60° C. The pressure at which the reaction is carried out can vary widely. In one embodiment, the reaction is carried out at a pressure in the range of 0.01 MPa to 10 MPa, for example, 0.1 MPa to 5 MPa. Preferably, the reaction is carried out at atmospheric pressure.

[0083] The acetoacetamide salt can be introduced into the cyclization reactor, and a cooled cyclization agent composition, for example a solution of the cyclization agent, optionally in a solvent, can be metered into the reactor. In a preferred embodiment, both reactants (acetoacetamide salt and cyclization agent) are fed simultaneously into the reactor. In one embodiment, the cooled cyclization agent composition is first introduced into the reactor and the acetoacetamide salt is added. Preferably, at least a portion of the cyclization agent composition is introduced into the reactor, and then the acetoacetamide salt and (further) cyclization agent are metered in, either continuously or in portions, preferably while maintaining the temperature as described above.

[0084] The acetoacetamide salt can be introduced into the reactor and the cyclizing agent composition can be metered into the reactor. In a preferred embodiment, both reactants are fed into the reactor simultaneously. In one embodiment, the cyclizing agent composition is first introduced into the reactor and the acetoacetamide salt is added. Preferably, at least a portion of the cyclizing agent composition is introduced into the reactor and then the acetoacetamide salt and (further) cyclizing agent are metered in, either continuously or in portions, preferably while maintaining the temperature as described above.

[0085]

[0080] Forming a crude acesulfame potassium composition from a cyclic sulfur trioxide adduct composition, in some embodiments, includes the steps of hydrolyzing the cyclic sulfur trioxide adduct to form an acesulfame-H composition; neutralizing the acesulfame-H in the acesulfame-H composition to form a crude acesulfame potassium composition; and forming an acesulfame potassium composition from the crude acesulfame potassium composition.

[0086] The cyclic sulfur trioxide adduct can be hydrolyzed by conventional means, for example with water. Thus, the forming process can include the step of hydrolyzing the cyclic sulfur trioxide adduct to form the acesulfame-H composition. Acesulfame-H is a sweetener. It is called acid.

[0087] A representative hydrolysis reaction scheme is shown in reaction (6) below.

[0088] [ka]

[0089]

[0083] Addition of water induces phase separation. The majority of the sweetener acid acesulfame-H (6-methyl-3,4-dihydro-1,2,3-oxathiazin-4-one 2,2-dioxide) formed by hydrolysis, e.g. at least 60% by weight, at least 70%, at least 80%, or at least 90%, is present in the organic phase. The remainder of the sweetener acid is present in the aqueous phase, which can be extracted and optionally added to the sweetener acid in the organic phase. When dichloromethane is used as the reaction medium, e.g. a molar excess of water or ice based on sulfur trioxide can be added to the cyclic sulfur trioxide adduct / sulfur trioxide solution.

[0090] In some cases, the hydrolysis step includes adding water to the cyclic sulfur trioxide adduct. In preferred embodiments, the weight ratio of water to acetoacetamide salt is greater than 1.3:1, e.g., greater than 1.5:1, greater than 1.7:1, greater than 2:1, or greater than 2.2:1. Use of these ratios can result in reduced formation of acetoacetamide-N-sulfonic acid and / or acetoacetamide in the neutralized crude acesulfame potassium composition, e.g., the crude acesulfame potassium composition can include the amounts of acetoacetamide-N-sulfonic acid discussed herein.

[0091] After the addition of water, the reaction solvent, e.g. dichloromethane, can be removed by distillation or the acesulfame-H remaining in the organic phase can be extracted with a more suitable solvent. Suitable solvents are those which are sufficiently stable to sulfuric acid and have a satisfactory dissolving capacity. Other suitable solvents are esters of carbonic acid, e.g. dimethyl carbonate, diethyl carbonate, and ethylene carbonate, or esters of organic monocarboxylic acids, e.g. isopropyl formate and isobutyl formate, ethyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, and neopentyl acetate, or esters of dicarboxylic acids or amides which are not miscible with water, e.g. tetrabutylurea. Isopropyl acetate and isobutyl acetate are particularly preferred.

[0092] The organic phases are combined, dried, for example with Na2SO4, and evaporated. The sulfuric acid carried over in the extraction can be removed by appropriately adding an aqueous alkali solution to the organic phase. For this purpose, dilute aqueous alkali can be added to the organic phase until the pH reached in the aqueous phase corresponds to that of the pure 6-methyl-3,4-dihydro-1,2,3-oxathiazin-4-one 2,2-dioxide at the same concentration in the same two-phase system of extractant and water.

[0093] Neutralization : Neutralization of acesulfame-H produces non-toxic salts of acesulfame-H, such as potassium acesulfame. In one embodiment, neutralization is carried out by reacting acesulfame-H with a suitable base, such as potassium hydroxide, particularly potassium hydroxide produced by the membrane process. Other suitable bases include, for example, KOH, KHCO3, K2CO3, A representative reaction scheme using potassium hydroxide as the neutralizing agent is shown in reaction (7) below.

[0094] [ka]

[0095] In one embodiment, acesulfame-H can be neutralized and extracted directly from the purified organic extract phase using an aqueous potassium base solution. Acesulfame potassium is then precipitated in crystalline form, if appropriate after evaporation of the solution, which can also be recrystallized for purification.

[0096] In one embodiment, the process is not a small batch process or a laboratory scale process. For example, the inventive method for producing a purified acesulfame potassium composition can produce at least 50 grams per batch, e.g., at least 100 grams per batch, at least 500 grams per batch, at least 1 kilogram per batch, or at least 10 kilograms per batch of purified acesulfame potassium composition. In terms of rate, the inventive method can produce at least 50 grams per hour, e.g., at least 100 grams per hour, at least 500 grams per hour, at least 1 kilogram per hour, or at least 10 kilograms per hour of purified acesulfame potassium composition.

[0097]

[0090] Figure 1 shows a representative acesulfame potassium process 100 according to the methods described herein. Process 100 includes an amidosulfamate formation reactor 102, and an acetoacetamide salt formation reactor 104. Although Figure 1 shows separate reactors for the two intermediate formation reactions, other configurations, such as a one-reactor process, are within the contemplation of the present method. Sulfamic acid is fed to amidosulfamate formation reactor 102 through sulfamic acid feed line 106. One or more amines, preferably triethylamine, are fed to amidosulfamate formation reactor 102 through amine feed line 108. In addition to sulfamic acid and one or more amines, acetic acid is also fed (through feed line 110) to amidosulfamate formation reactor 102. The resulting reaction mixture in amidosulfamate formation reactor 102 is as discussed above. In amidosulfamate-forming reactor 102, sulfamic acid and an amine are reacted (in the presence of acetic acid) to produce a crude amidosulfamate composition that exits reactor 102 via line 112. Although not shown, a reaction solvent, such as dichloromethane, may also be present in amidosulfamate-forming reactor 102.

[0098] The crude amidosulfamate composition in line 112 is sent to the acetoacetamide salt-forming reactor 104. Diketene is fed to the acetoacetamide salt-forming reactor 104 through feed line 114. In the acetoacetamide salt-forming reactor 104, the amidosulfamate and diketene react to produce a crude acetoacetamide salt composition which exits the reactor 104 through line 118. Although not shown, dichloromethane can also be present in the acetoacetamide salt-forming reactor 104.

[0099]

[0092] Through supply lines 121 and 123, a cyclizing agent (sulfur dioxide) and a solvent (dichloromethane) are fed to vessel 119. Vessel 119 is preferably the vessel in which a cyclizing agent composition comprising these two components is formed. Through line 125, the cyclizing agent composition comprising both the cyclizing agent and the solvent is discharged from vessel 119.

[0100]

[0093] The crude acetoacetamide salt composition is fed via line 118 to cyclization reactor 120. A cyclization agent composition is also fed (via line 125) to cyclization reactor 120. Line 125 is preferably formed of materials and sized and shaped to facilitate the residence times discussed herein. Within cyclization reactor 120, the acetoacetamide salts in the crude acetoacetamide salt composition in line 118 are cyclized to discharge a cyclic sulfur trioxide adduct stream via line 124.

[0101]

[0094] The cyclic sulfur trioxide adduct in line 124 is fed to a hydrolysis reactor 126. Water is fed to the hydrolysis reactor 126 through a water feed line 128. In the hydrolysis reactor 126, the cyclic sulfur trioxide adduct is hydrolyzed to produce a crude acesulfame-H composition which is discharged from the hydrolysis reactor 126 through line 130 and fed to a phase separation unit 132. The phase separation unit 132 separates the contents of line 130 into an organic phase 134 and an aqueous phase 136. The organic phase 134 contains a major amount of the acesulfame-H in line 130 and a solvent, such as methylene chloride. The aqueous phase 136 is discharged through line 137 and contains triethylammonium sulfate, and optionally sulfuric acid and small amounts of acesulfame-H. The aqueous phase can be further purified to separate and / or recover acesulfame-H and / or triethylammonium sulfate. The recovered acesulfame-H can be combined with the acesulfame from the organic phase (not shown).

[0102]

[0095] Organic phase 134 is discharged from phase separation unit 132 and sent (through line 140) to extraction column 138. Water is supplied to extraction column 138 through water supply line 142. The water extracts residual sulfate from the contents of line 140 and a purified acesulfame-H composition is discharged from extraction column 138 through line 144. The extracted sulfate is discharged from extraction column 138 through line 145.

[0103]

[0096] The purified acesulfame-H composition in line 144 is sent to neutralization unit 146, which is also provided with potassium hydroxide (through line 148). The addition of potassium hydroxide to neutralization unit 146 (through line 148) can be adjusted to achieve and / or maintain a desired pH level during the neutralization discussed herein. The potassium hydroxide neutralizes the acesulfame-H in the purified acesulfame-H composition to produce a product comprising acesulfame potassium, dichloromethane, water, potassium hydroxide, and impurities such as acetoacetamide-N-sulfonic acid or acetoacetamide, which exits neutralization unit 146 through line 150. This product can be considered a crude acesulfame potassium composition.

[0104] The crude acesulfame potassium product stream in line 150 may be sent to a processing section 156 to recover purified acesulfame potassium (shown exiting stream 152). In addition to the purified acesulfame potassium, dichloromethane and potassium hydroxide may be separated from the crude acesulfame potassium product stream, as shown by stream 154. The contents of stream 154 may be recovered and / or recycled to the process. Processing section 156 may include one or more of the processing operations described herein, such as stripping. These procedures may include purification, evaporation, crystallization, and filtration.

[0105]

[0098] The product in line 150 is sent to a phase separation unit 160. Phase separation unit 160 separates the product in line 150 into an organic phase 162 and an aqueous phase 164. The aqueous phase 164 contains the majority of the acesulfame potassium in line 150 and some impurities. The organic phase 162 contains potassium hydroxide, dichloromethane, and water, and can be further processed to recover these components. The aqueous phase 164 (without further processing) can be considered a crude acesulfame potassium composition. The aqueous phase 164 can optionally be processed to form a purified acesulfame potassium composition.

[0106]

[0099] Aqueous phase 164 is sent via line 166 to processing unit 156. In processing unit 156, aqueous phase 164 is processed to obtain a purified acesulfame potassium composition (a product that can be sold), shown as being discharged via stream 152. In addition to the purified acesulfame potassium composition, dichloromethane and potassium hydroxide can be separated. These components exit processing unit 156 via line 154. The contents of stream 154 can be recovered and / or recycled to the process.

[0107]

[0100] The present invention also relates to the following aspects. Form 1: A method for producing a purified acesulfame potassium composition, comprising the steps of: (a) forming a cyclic sulfur trioxide adduct; (b) hydrolyzing the cyclic sulfur trioxide adduct to form an acesulfame-H composition comprising acesulfame-H; (c) neutralizing the acesulfame-H in the acesulfame-H composition to form a crude acesulfame potassium composition comprising acesulfame potassium and less than 2800 wppm acetoacetamido-N-sulfonic acid, wherein the neutralizing step is conducted at a pH of 11.0 or less; and (d) treating the crude acesulfame potassium composition to form a purified acesulfame potassium composition comprising acesulfame potassium and less than 37 wppm acetoacetamido-N-sulfonic acid; The above method comprising the steps of:

[0108]

[0102] Form 2: The neutralization step (c) reacting acesulfame-H with a neutralizing agent in an acesulfame-H / neutralizing agent reaction mixture to form an acesulfame potassium composition; 2. The method of claim 1, comprising:

[0109]

[0103] Form 3: The method of any of the above forms, wherein the neutralizing agent comprises potassium hydroxide.

[0104] Form 4: The process of any of the above forms, wherein said potassium hydroxide is produced by a membrane process and said purified acesulfame potassium composition contains less than 10 wppm mercury.

[0110]

[0105] Form 5: The method of any of the above forms, wherein the acesulfame-H / neutralizing agent reaction mixture comprises 1% to 95% by weight of neutralizing agent, and 1% to 95% by weight of acesulfame-H, based on the total weight of the acesulfame-H / neutralizing agent reaction mixture.

[0111]

[0106] Form 6: The process of any of the above forms, wherein the neutralizing step (c) comprises neutralizing the acesulfame-H in the acesulfame-H composition to form the crude acesulfame potassium composition further comprising acetoacetamide.

[0112]

[0107] Form 7: The crude acesulfame potassium composition contains 500 wppm to 2375 wppm of acetoacetamido-N-sulfonic acid, and the purified acesulfame potassium composition The process of any of the above forms, wherein the article contains less than 25 wppm of acetoacetamide-N-sulfonic acid and further contains less than 25 wppm of acetoacetamide.

[0113]

[0108] Form 8: The process of any of the above forms, wherein the neutralization step (c) is carried out at a pH in the range of 9.0 to 11.0, and the crude acesulfame potassium composition contains 20 wppm to 2500 wppm of acetoacetamide-N-sulfonic acid, and the purified acesulfame potassium composition contains less than 25 wppm of acetoacetamide-N-sulfonic acid and less than 15 wppm of acetoacetamide.

[0114]

[0109] Form 9: The process of any of the above forms, wherein the neutralization step (c) is carried out at a pH in the range of 8 to 10.3, and the crude acesulfame potassium composition contains 600 wppm to 1200 wppm of acetoacetamide-N-sulfonic acid, and the purified acesulfame potassium composition contains less than 10 wppm of acetoacetamide-N-sulfonic acid and less than 10 wppm of acetoacetamide.

[0115]

[0110] Form 10: The process of any of the above forms, wherein the neutralization step (c) is carried out at a pH in the range of 8 to 10.3, and the crude acesulfame potassium composition contains less than 2400 wppm acetoacetamide-N-sulfonic acid, and the purified acesulfame potassium composition contains less than 10 wppm acetoacetamide-N-sulfonic acid and less than 10 wppm acetoacetamide.

[0116]

[0111] Form 11: The method of any of the above forms, wherein said purified acesulfame potassium composition contains less than 37 wppm acetoacetamide.

[0112] Form 12: The process of any of the above forms, wherein said neutralization step (c) is carried out at a pH in the range of 9.0 to 11.0.

[0117]

[0113] Form 13: The process of any of the above forms, wherein said neutralization step (c) is carried out at a pH in the range of 9.0 to 10.5.

[0114] Form 14: The process of any of the above forms, wherein said neutralization step (c) is carried out at a pH in the range of 8.0 to 10.3.

[0118]

[0115] Mode 15: The process of any of the above modes, wherein said treating step (d) is carried out at a temperature below 90°C.

[0116] Form 16: The process of any of the above forms, wherein said treating step (d) comprises an evaporation step using a residence time of less than 180 minutes.

[0119]

[0117] Form 17: The process of any of the above forms, wherein said neutralization step is maintained at a pH of 11.0 or less. Form 18: A purified acesulfame potassium composition produced or capable of being produced or obtainable or obtainable by the process of any of Forms 1-17.

[0120] Form 19: A method for producing a purified acesulfame potassium composition, comprising the steps of: (a) reacting sulfamic acid with triethylamine to form an amidosulfamate salt; (b) reacting the amidosulfamate with diketene to form an acetoacetamide salt; (c) contacting dichloromethane with sulfur trioxide to form a cyclization agent composition; (d) reacting the acetoacetamide salt with sulfur trioxide in the cyclizing agent composition to form a cyclic sulfur trioxide adduct; (e) hydrolyzing the cyclic sulfur trioxide adduct to form an acesulfame-H composition comprising acesulfame-H; (f) neutralizing said acesulfame-H in said acesulfame-H to form a crude acesulfame potassium composition comprising acesulfame potassium and less than 2800 wppm acetoacetamido-N-sulfonic acid, wherein the neutralizing step is conducted at a pH of 11.0 or less; (g) treating the crude acesulfame potassium composition to form a purified acesulfame potassium composition comprising acesulfame potassium and less than 37 wppm acetoacetamido-N-sulfonic acid; Includes; The above method, wherein steps (a), (b), and (c) can be performed in any order before performing step (d).

[0121]

[0120] Form 20: The process of Form 19, wherein said purified acesulfame potassium composition further comprises less than 20 wppm of acetoacetamide.

[0121] Form 21: The process of any of the above forms, wherein the neutralization step (f) is carried out at a pH in the range of 9.0 to 11.0, and wherein the crude acesulfame potassium composition contains 20 wppm to 2500 wppm of acetoacetamide-N-sulfonic acid, and the purified acesulfame potassium composition contains less than 25 wppm of acetoacetamide-N-sulfonic acid and less than 15 wppm of acetoacetamide.

[0122] Form 22: An acesulfame potassium composition comprising acesulfame potassium and less than 25 wppm acetoacetamide-N-sulfonic acid, and less than 25 wppm acetoacetamide.

[0123]

[0123] Form 23: The acesulfame potassium composition of Form 22, further comprising from 0.001 wppm to 5 wppm of organic impurities, and / or from 0.001 wppm to 5 wppm of at least one heavy metal.

[0124] Form 24: The acesulfame potassium composition of any of the above forms, wherein said at least one heavy metal is selected from the group consisting of mercury, lead, and mixtures thereof.

[0125] Form 25: The acesulfame potassium composition of any of the above forms, wherein said mercury is present in an amount from 1 wppb to 20 wppm.

[0125]

[0126] Form 26: The acesulfame potassium composition of any of the above forms, wherein said lead is present in an amount from 1 wppb to 25 wppm. EXAMPLES

[0126]

[0127] The following examples are included to illustrate the processes and compositions and are not intended to limit the scope of the application. Examples 1a-c and Comparative Example A :

[0128] 100 mmol of sulfamic acid, 99.5% pure, was suspended in 50 mL of dichloromethane in a flask under reflux. Under continuous stirring, 105 mmol of trimethylamine was added within about 3 minutes. During this time, the temperature rose to about 42° C. (the boiling point of dichloromethane) due to an exothermic acid / base reaction. The first reaction mixture was stirred for about 15 more minutes until no solid precipitate was observed in the flask. Next, 10 mmol of acetic acid was added to the first reaction mixture and stirred for about 15 more minutes. At this point, 110 mmol of diketene was added dropwise within 7 minutes of the acetic acid addition to form a second reaction mixture. All of the diketene was added to the second reaction mixture and after about 15 minutes of reaction time, the second reaction mixture was cooled. The resulting cooled second reaction mixture contained about 30% acetoacetamide-N- The sulfonate triethylammonium salt was added to the cooled second reaction mixture, which was then mixed with the cooled mixture and cooled for 2 hours at 30° C. Additional batches of the cooled second reaction mixture were prepared as needed.

[0127]

[0129] A sulfur trioxide / dichloromethane composition containing about 15% by weight sulfur trioxide and about 85% by weight dichloromethane was prepared by contacting the two components with each other in a separate container.

[0128]

[0130] A second flask (a 4-neck round bottom flask fitted with a mechanical stirrer, a thermometer, and a feed vessel) was placed in a cooling bath containing a mixture of isopropanol and dry ice. Approximately 200 g of the acetoacetamide-N-sulfonate triethylammonium salt solution and approximately 577 g of the sulfur trioxide / dichloromethane composition were weighed out. Approximately 15% by weight (approximately 87 g) of the total sulfur trioxide / dichloromethane composition was first fed into the reaction flask under continuous stirring with a mechanical stirrer. When the temperature of the flask contents reached -35°C (by cooling batch), the remainder of the sulfur trioxide / dichloromethane composition and all of the acetoacetamide-N-sulfonate triethylammonium salt solution were fed into the second flask. The solvent was in contact with the cyclization agent for less than one hour prior to the formation of the cyclic sulfur trioxide adduct, e.g., before the acetoacetamide-N-sulfonate triethylammonium salt solution was fed to the second flask. The feed rate was controlled such that the temperature of the contents of the second flask was maintained between −25° C. and −35° C. during the feed / cyclization reaction. After the reactants were fed, the reaction was allowed to proceed for approximately an additional minute. The cooling bath was then removed.

[0129]

[0131] After about 1 minute, the temperature of the flask contents reached about -22°C. At this point, the hydrolysis was initiated by feeding deionized water to the flask. The water was fed over a period of 10 minutes. The hydrolysis reaction was exothermic. The water was added slowly such that the temperature was maintained between -20°C and -5°C. After the water was added, the reaction mixture was allowed to reach room temperature.

[0130]

[0132] The weight ratio of water added for hydrolysis to acetoacetamide-N-sulfonate triethylammonium salt in dichloromethane solution was kept constant for Examples 1a-c and Comparative Example A.

[0131]

[0133] The hydrolysis products were phase separated using a separatory funnel: the heavier organic sweetener acid-dichloromethane phase (acesulfame-H composition) was separated off and the remaining aqueous phase was discarded.

[0132]

[0134] The acesulfame-H in the acesulfame-H composition was neutralized with 10% potassium hydroxide solution. Neutralization was performed at 25° C.±1° C. The addition of potassium hydroxide was completed within 20 minutes. Neutralization was performed at various pH levels as shown in Table 1.

[0133]

[0135] After the neutralization step was completed, further phase separation was performed using a separatory funnel to obtain an aqueous phase containing acesulfame potassium (and some impurities), and an organic phase. The aqueous phase was considered the crude acesulfame potassium composition in Table 1. The remaining dichloromethane in the organic phase was discarded.

[0134]

[0136] The crude acesulfame potassium samples of Examples 1a-c and Comparative Example A were tested for acetoacetamido-N-sulfonic acid content. Testing was performed using the HPLC equipment and techniques discussed herein. In particular, HPLC analysis was performed using a Shimadzu LC Systems HPLC unit equipped with a CBM-20 Shimadzu controller and an IonPac NS1 ((5 μm) 150×4 mm) analytical column and an IonPac NG1 guard column (35×4.0 mm). For detection (at wavelengths of 270 nm and 280 nm), a Shimadzu SPD-M20A photodiode array detector was used. The analysis was performed at a column temperature of 23° C. As the first eluent, an aqueous mixture of tetrabutylammonium hydrogen sulfate (3.4 g / L), acetonitrile (300 mL / L), and potassium hydroxide (0.89 g / L) was used; as the second eluent, an aqueous mixture of tetrabutylammonium hydrogen sulfate (3.4 g / L) and potassium hydroxide (0.89 g / L) was used. Calculations were performed using Shimadzu's LabSolution software. Elution was performed in gradient mode according to the following second eluent flow profile:

[0135] · 0–3 min: constant at 80% (v / v); 3-6 min: Linear decrease to 50% (v / v); · 6–15 min: constant at 50% (v / v); 15-18 minutes: Linear decrease to 0%; 18-22 min: constant at 0%; 22–24 min: linear increase to 80% (v / v); 24~35 min: constant at 80% (v / v).

[0136] The total eluent flow rate was approximately 1.2 mL / L. Data collection and calculations were performed using Shimadzu LabSolution software.

[0137] The results are shown in Table 1.

[0137] [Table 1]

[0138] As shown in Table 1, when the neutralization step is carried out at a pH of 11.0 or less, the acetoacetamido-N-sulfonic acid content in the resulting crude acesulfame potassium composition is much lower than when a higher pH is used, with a minimum of 23% lower (Comparative Example A vs. Example 1c: 3066-2361 / 3066=23%).

[0139] Importantly, the reduced acetoacetamide-N-sulfonic acid content in the crude acesulfame potassium composition concomitantly reduces the formation of acetoacetamide (e.g., by decomposition of acetoacetamide-N-sulfonic acid) in subsequent separation operations, thereby resulting in a reduced acetoacetamide content in the resulting purified acesulfame potassium composition.

[0139]

[0140] Although the present invention has been described in detail, modifications within the spirit and scope of the invention will be readily apparent to those skilled in the art. In view of the above discussion, the relevant knowledge in the art, and the references discussed above in connection with the background and detailed description (all of which are incorporated herein by reference). Furthermore, it should be understood that the various aspects of the invention and the various aspects and various parts of the various features set forth above and / or in the appended claims can be combined or exchanged in whole or in part. As will be appreciated by those skilled in the art, in the above description of the various aspects, other aspects are shown and these aspects can be appropriately combined with other aspects. Furthermore, those skilled in the art will recognize that the above description is for illustrative purposes only and is not intended to limit the present invention. The following is a transcription of the claims as of the filing of this application. [1] A method for producing a purified acesulfame potassium composition, comprising the steps of: (a) forming a cyclic sulfur trioxide adduct; (b) hydrolyzing the cyclic sulfur trioxide adduct to form an acesulfame-H composition comprising acesulfame-H; (c) neutralizing the acesulfame-H in the acesulfame-H composition to form a crude acesulfame potassium composition comprising acesulfame potassium and less than 2800 wppm acetoacetamido-N-sulfonic acid, wherein the neutralizing step is conducted at a pH of 11.0 or less; and (d) treating the crude acesulfame potassium composition to form a purified acesulfame potassium composition comprising acesulfame potassium and less than 37 wppm acetoacetamido-N-sulfonic acid; The above method comprising the steps of: [2] The neutralization step (c) is reacting acesulfame-H with a neutralizing agent in an acesulfame-H / neutralizing agent reaction mixture to form said acesulfame potassium composition; The method according to claim 1, comprising: [3] The method according to [2], wherein the neutralizing agent comprises potassium hydroxide. [4] The method of [3], wherein the potassium hydroxide is produced by a membrane process and the purified acesulfame potassium composition contains less than 10 wppm of mercury. [5] The method according to [2], wherein the acesulfame-H / neutralizing agent reaction mixture contains 1% by weight to 95% by weight of neutralizing agent, and 1% by weight to 95% by weight of acesulfame-H, based on the total weight of the acesulfame-H / neutralizing agent reaction mixture. [6] The method of [1], wherein the neutralizing step (c) comprises neutralizing the acesulfame-H in the acesulfame-H composition to form the crude acesulfame potassium composition further comprising acetoacetamide. [7] The method of [6], wherein the crude acesulfame potassium composition contains between 500 wppm and 2375 wppm of acetoacetamide-N-sulfonic acid, and the purified acesulfame potassium composition contains less than 25 wppm of acetoacetamide-N-sulfonic acid and further contains less than 25 wppm of acetoacetamide. [8] The method of [6], wherein the neutralization step (c) is carried out at a pH in the range of 9.0 to 11.0, and the crude acesulfame potassium composition contains 20 wppm to 2500 wppm of acetoacetamide-N-sulfonic acid, and the purified acesulfame potassium composition contains less than 25 wppm of acetoacetamide-N-sulfonic acid and less than 15 wppm of acetoacetamide. [9] The method of [6], wherein the neutralization step (c) is carried out at a pH in the range of 8 to 10.3, and the crude acesulfame potassium composition contains 600 wppm to 1200 wppm of acetoacetamide-N-sulfonic acid, and the purified acesulfame potassium composition contains less than 10 wppm of acetoacetamide-N-sulfonic acid and less than 10 wppm of acetoacetamide.

[10] The method of [6], wherein the neutralization step (c) is carried out at a pH in the range of 8 to 10.3, and the crude acesulfame potassium composition contains less than 2400 wppm acetoacetamide-N-sulfonic acid and the purified acesulfame potassium composition contains less than 10 wppm acetoacetamide-N-sulfonic acid and less than 10 wppm acetoacetamide.

[11] The method of [6], wherein the purified acesulfame potassium composition contains less than 37 wppm acetoacetamide.

[12] The method according to [1], wherein the neutralization step (c) is carried out at a pH in the range of 9.0 to 11.0.

[13] The method according to [1], wherein the neutralization step (c) is carried out at a pH in the range of 9.0 to 10.5.

[14] The method according to [1], wherein the neutralization step (c) is carried out at a pH in the range of 8.0 to 10.3.

[15] The method according to [1], wherein the treating step (d) is carried out at a temperature below 90°C.

[16] The method of [1], wherein the treating step (d) comprises an evaporation step using a residence time of less than 180 minutes.

[17] The method according to [1], wherein the neutralization step is maintained at a pH of 11.0 or less.

[18] A purified acesulfame potassium composition produced by the method described in [1].

[19] A method for producing a purified acesulfame potassium composition, comprising the steps of: (a) reacting sulfamic acid with triethylamine to form an amidosulfamate salt; (b) reacting the amidosulfamate with diketene to form an acetoacetamide salt; (c) contacting dichloromethane with sulfur trioxide to form a cyclization agent composition; (d) reacting the acetoacetamide salt with sulfur trioxide in the cyclizing agent composition to form a cyclic sulfur trioxide adduct; (e) hydrolyzing the cyclic sulfur trioxide adduct to form an acesulfame-H composition comprising acesulfame-H; (f) neutralizing said acesulfame-H in said acesulfame-H to form a crude acesulfame potassium composition comprising acesulfame potassium and less than 2800 wppm acetoacetamido-N-sulfonic acid, wherein the neutralizing step is conducted at a pH of 11.0 or less; (g) treating said crude acesulfame potassium composition to form said purified acesulfame potassium composition comprising acesulfame potassium and less than 37 wppm acetoacetamido-N-sulfonic acid; Includes; The above method, wherein steps (a), (b), and (c) can be performed in any order before performing step (d).

[20] The method of

[19] , wherein the purified acesulfame potassium composition further contains less than 20 wppm of acetoacetamide.

[21] The method of

[20] , wherein the neutralization step (f) is carried out at a pH in the range of 9.0 to 11.0, and the crude acesulfame potassium composition contains 20 wppm to 2500 wppm of acetoacetamide-N-sulfonic acid, and the purified acesulfame potassium composition contains less than 25 wppm of acetoacetamide-N-sulfonic acid and less than 15 wppm of acetoacetamide.

[22] An acesulfame potassium composition comprising acesulfame potassium and less than 25 wppm of acetoacetamide-N-sulfonic acid, and less than 25 wppm of acetoacetamide.

[23] The acesulfame potassium composition according to

[22] , further comprising 0.001 wppm to 5 wppm of organic impurities and / or 0.001 wppm to 5 wppm of at least one heavy metal.

[24] The acesulfame potassium composition according to

[23] , wherein the at least one heavy metal is selected from the group consisting of mercury, lead, and mixtures thereof.

[25] The acesulfame potassium composition according to

[24] , wherein the mercury is present in an amount of 1 wppb to 20 wppm. "26] The acesulfame potassium composition according to

[24] , wherein the lead is present in an amount of 1 wppb to 25 wppm.

Claims

1. 1. A method for producing a purified acesulfame potassium composition, comprising: (a) forming a cyclic sulfur trioxide adduct; (b) hydrolyzing the cyclic sulfur trioxide adduct to form an acesulfame-H composition comprising acesulfame-H; (c) neutralizing the acesulfame-H in the acesulfame-H composition to form a crude acesulfame potassium composition comprising acesulfame potassium and less than 2800 wppm acetoacetamido-N-sulfonic acid, wherein the neutralizing step is conducted at a pH of 11.0 or less; and (d) treating the crude acesulfame potassium composition to form the purified acesulfame potassium composition comprising acesulfame potassium, less than 37 wppm acetoacetamide-N-sulfonic acid, and less than 37 wppm acetoacetamide; Including, The process of claim 5, wherein said process step (d) comprises an evaporation step using a residence time of less than 180 minutes, and said process step (d) is carried out at a temperature below 90°C.

2. The neutralization step (c) reacting acesulfame-H with a neutralizing agent in an acesulfame-H / neutralizing agent reaction mixture to form said acesulfame potassium composition; The method of claim 1 , comprising:

3. The method of claim 2 , wherein the neutralizing agent comprises potassium hydroxide.

4. 4. The method of claim 3, wherein the potassium hydroxide is produced by a membrane process and the purified acesulfame potassium composition contains less than 10 wppm mercury.

5. 3. The method of claim 2, wherein the acesulfame-H / neutralizing agent reaction mixture comprises from 1% to 95% neutralizing agent and from 1% to 95% acesulfame-H, by weight, based on the total weight of the acesulfame-H / neutralizing agent reaction mixture.

6. 2. The method of claim 1, wherein the neutralizing step (c) comprises neutralizing the acesulfame-H in the acesulfame-H composition to form the crude acesulfame potassium composition further comprising acetoacetamide.

7. 7. The method of claim 6, wherein the crude acesulfame potassium composition comprises from 500 wppm to 2375 wppm acetoacetamide-N-sulfonic acid and the purified acesulfame potassium composition comprises less than 25 wppm acetoacetamide-N-sulfonic acid and further comprises less than 25 wppm acetoacetamide.

8. 7. The method of claim 6, wherein the neutralizing step (c) is conducted at a pH in the range of from 9.0 to 11.0, and wherein the crude acesulfame potassium composition contains from 20 wppm to 2500 wppm acetoacetamide-N-sulfonic acid and the purified acesulfame potassium composition contains less than 25 wppm acetoacetamide-N-sulfonic acid and less than 15 wppm acetoacetamide.

9. 7. The method of claim 6, wherein the neutralizing step (c) is conducted at a pH in the range of from 8 to 10.3, the crude acesulfame potassium composition comprises from 600 wppm to 1200 wppm acetoacetamide-N-sulfonic acid, and the purified acesulfame potassium composition comprises less than 10 wppm acetoacetamide-N-sulfonic acid and less than 10 wppm acetoacetamide.

10. 7. The method of claim 6, wherein the neutralizing step (c) is conducted at a pH in the range of 8 to 10.3, and wherein the crude acesulfame potassium composition contains less than 2400 wppm acetoacetamide-N-sulfonic acid and the purified acesulfame potassium composition contains less than 10 wppm acetoacetamide-N-sulfonic acid and less than 10 wppm acetoacetamide.

11. 2. The process of claim 1, wherein the neutralization step (c) is carried out at a pH in the range of 9.0 to 11.

0.

12. 2. The process of claim 1, wherein the neutralization step (c) is carried out at a pH in the range of 9.0 to 10.

5.

13. 2. The process of claim 1, wherein the neutralization step (c) is carried out at a pH in the range of 8.0 to 10.

3.

14. 1. A method for producing a purified acesulfame potassium composition, comprising: (a) reacting sulfamic acid with triethylamine to form an amidosulfamate salt; (b) reacting the amidosulfamate with diketene to form an acetoacetamide salt; (c) contacting dichloromethane with sulfur trioxide to form a cyclization agent composition; (d) reacting the acetoacetamide salt with sulfur trioxide in the cyclizing agent composition to form a cyclic sulfur trioxide adduct; (e) hydrolyzing the cyclic sulfur trioxide adduct to form an acesulfame-H composition comprising acesulfame-H; (f) neutralizing said acesulfame-H in said acesulfame-H to form a crude acesulfame potassium composition comprising acesulfame potassium and less than 2800 wppm acetoacetamido-N-sulfonic acid, wherein the neutralizing step is conducted at a pH of 11.0 or less; (g) treating the crude acesulfame potassium composition to form the purified acesulfame potassium composition comprising acesulfame potassium, less than 37 wppm acetoacetamide-N-sulfonic acid, and less than 37 wppm acetoacetamide; Including; said treating step (g) comprising an evaporation step using a residence time of less than 180 minutes, said treating step (g) being carried out at a temperature below 90° C.; The above method, wherein steps (a), (b), and (c) can be performed in any order before performing step (d).

15. 15. The method of claim 14, wherein the purified acesulfame potassium composition further comprises less than 20 wppm acetoacetamide.

16. 16. The method of claim 15, wherein the neutralizing step (f) is conducted at a pH in the range of 9.0 to 11.0, the crude acesulfame potassium composition comprises 20 wppm to 2500 wppm acetoacetamide-N-sulfonic acid, and the purified acesulfame potassium composition comprises less than 25 wppm acetoacetamide-N-sulfonic acid and less than 15 wppm acetoacetamide.

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