KR20010052586A - Preparation and purificaton of a salt of aspartame with acesulfam k - Google Patents

Abstract

The present invention relates to a process for preparing salts of acesulfame acid and aspartame in solid and dry form, prepared in a liquid medium by solid liquid separation and drying, and thereafter separated as a wet solid product.

The salts of acesulfamic acid and aspartame can be used as wet solid crystalline products which when dried form a product having a particle-size distribution with at least 10 wt.% Of the particles being at least 200 μm,

The crystalline product has improved stability compared to conventional products,

In one embodiment, the wet solid crystalline product is subjected to washing with a basic aqueous solution having a pH of at least 8 prior to drying.

The present invention also relates to salts of acesulfameic acid and aspartame having an improved stability when the salt in dry form is heated at 80 ° C. for 48 hours with an acetoacetamide content of 10 ppm or less by dry weight of salt. The salts of acesulfamic acid and aspartame are characterized by having a particle-size distribution with at least 10 wt.% And especially at least 25 wt.% Of the particles having at least 200 μm.

Description

Preparation and Purification of Salts of Acesulfame K and Aspartame {PREPARATION AND PURIFICATON OF A SALT OF ASPARTAME WITH ACESULFAM K}

The present invention relates to a process for preparing salts of acesulfame acid and aspartame in solid and dry form by solid liquid separation, which are prepared in a liquid medium, separated therefrom as a wet solid product and then dried. According to the invention, salts of acesulfame acids and aspartame with improved stability in dry form are obtained by reducing the risk that acetoacetamide is formed when the salt is exposed to high temperatures. The present invention also relates to salts of the acesulfame acids and aspartame.

Salts of acesulfame and aspartame are sweeteners with a sensitivity of approximately 200 times the weight-based sugars, and are particularly suitable for use in powdered mixtures, chewing gums, sweets and dry foods, and in addition to sweeteners, compounds such as aldehydes, etc. And a variety of preparations that cause undesirable reactions with sweeteners such as aspartame.

The salts of acesulfamic acid and aspartame consist of the sweetener aspartame, the α-L-aspartyl-L-phenylalanine methyl ester (hereinafter referred to as APM) and acesulfamic acid, which have long been known. Acesulfame acid is potassium with the sweetener acesulfame-K, 6-methyl-1,2,3-oxathiazine-4 (3K) -one-2,2-dioxide (hereinafter referred to as AceK). Acids derived from salts and are well known. Acesulfame acid is hereinafter referred to as AceH and salts of APM and AceH will be referred to as APM.Ace.

A method for producing APM. Ace in the form with good thermal stability and low hygroscopicity is described in EP-A-0768041. In the process for preparing APM.Ace described in EP-A-0768041, the salt is obtained as a solid as a result of the trans-salification process carried out in a liquid medium. The reaction system used (usually a slurry) consists of (i) aspartame, (ii) inorganic salts of acesulfame acid, for example potassium salts and (iii) hydrochloric acid as components. The components can be added to the reaction system in a specific desired order, the system being stirred while keeping the motion constant, so that the components are distributed relatively homogeneously, and the desired concentration of the acid rising too high. The effect may not occur. The process for preparing APM.Ace according to the patent application is relatively always carried out in an aqueous medium at a temperature in the range of -20 to + 90 ° C by a fast method as described in the above application. The patent application describes that the order of addition of the components in the reaction and the way in which the first solid APM.Ace is obtained as a slurry is not critical. EP-A-0768041 does not describe much information resulting from the recovery, drying and / or further purification of the formed APM.Ace. The standard methods used, such as washing solids obtained by filtration with ice water and the methods described in this patent application, fully satisfy the conditions for obtaining products with good thermal stability with respect to the thermal properties of the APM portion of the salt. Let's do it.

EP-A-0768041 relates to the thermal stability associated with the APM portion of the salt, where it is known that the thermal stability of APM is significantly lower than that of AceK. It is also known that acesulfame acid (AceH), an acid corresponding to AceK, has a lower stability than, for example, AceK. Ace sections in APM.Ace exist in the same way as in AceK, so no specific degradation products of Ace sections in APM.Ace are provided.

According to EP-A-0768041, APM, Ace (dry form) has good thermal stability when degradation of less than 0.5% occurs when heated at 120 ° C. for 1 hour or at 70 ° C. for 70 hours. Decomposition of the Ace moiety of APM.Ace is evident as demonstrated in the tables of Comparative Experiments 1C and 1D of the patent application, conducted in methanol.

However, on the other hand, detectable acetoacetamide concentrations above the detection limit of 10 ppm by dry weight basis of APM.Ace are, for example, at low moisture content of dry APM.Ace prepared in a dry form by the method according to EP-A-0768041. Formed in APM.Ace when further exposed to high temperatures such as 80 ° C. (especially referred to below as standard conditions) for a period of time. Acetoacetamide will hereinafter be referred to as 3A.

In foodstuffs, ie substances used in foodstuffs, in particular the presence of acetoacetamide is limited to low concentrations due to toxicity. According to the European Pharmacopoeia for Acetoacetamide (Supplement 1998), the maximum allowable concentration is 1250 ppm. Therefore, in the foregoing, it is important to prevent the formation of a detectable concentration of 3A in APM.Ace because the applicant automatically and rapidly advances the formation of acetoacetamide as the existing concentration becomes higher.

It is an object of the present invention to solve the above mentioned problems and in particular to prevent or prevent the formation of 3A in APM.Ace.

Surprisingly, the object is achieved in that when dried, salts of acesulfame acid and aspartame are prepared as wet solid crystalline products which produce a product having a particle-size distribution in a dry form in which at least 10 wt.% Of the particles are at least 200 μm. .

APM.Ace having a particle-size distribution (hereinafter, referred to as a psd) in a dry form having at least 10 wt.% Of the particles at least 200 μm in the dry form may be exposed to a long dry form at high temperatures such as 48 hours at 80 ° C. When satisfying that APM.Ace should not have a 3A content of more than 10ppm by dry weight basis of APM.Ace.

At temperatures below 80 ° C., for example 70 ° C., the formation of 3A in APM.Ace proceeds more slowly, according to Applicants' observation, and even at lower temperatures, the effect of its formation is almost negligible. For example, storing APM.Ace (prepared according to the present invention) at 60 ° C. for 12 months produces 3A in undetectable concentrations, while APM.Ace not prepared according to the present invention is present at 60 ° C. Already contains 10-20 ppm of 3A. While storing APM.Ace for one year at 40 ° C., 3A is not formed in a detectable amount in APM.Ace, which initially did not contain 3A.

According to the applicant, the formation of 3A can be explained as a result of the small amount of reaction of AceH present. Under the influence of (two molecules) of water, acetoacetamide-N-sulfonic acid can be formed from (one molecule) AceH, and the acid can be subsequently reacted to form acetoacetamide. Applicants now know that the reaction is autocatalytic.

As mentioned in EP-A-0768041, it is noted that if prepared similarly to the method described in ES-A-8604766, the moisture content of APM.Ace is higher than that by the method according to EP-A-0768041. . Therefore, the formation of the problem 3A under the conditions of storage and prolonged heating is more in this case.

The particle-size distribution (p.s.d.) of APM.Ace in dry form can be measured by any method conventionally used by those skilled in the art. A very simple method for measuring the wt.% Of APM.Ace in dry form with a particle size of 200 μm or more is to remove 10 g of APM.Ace conventionally on a screen having a mesh width of 200 μm and to remain on the screen. The step of measuring the weight fraction is made. APM.Ace in dry form is a rotary evaporator, after normal drying under relaxed conditions when APM.Ace is obtained as a wet slurry, or when APM.Ace is recovered by evaporation from solution, depending on how APM.Ace is prepared herein. Is understood to mean APM.Ace after normal drying using.

Applicants have found that there is no method for producing APM. Ace in which a product with p.s.d. in which at least 10 wt.% Of the particles in the dry form is at least 200 μm is obtained. In the study framework for the present invention, the inventors found that a specific measurement was found as described below to obtain APM.Ace with p.s.d. in which at least 10.wt.% of the particles in dry form were 200 μm or more.

Therefore, European Patent EP-A-0768041 describes a number of experimental examples for preparing APM.Ace, but in most cases the reaction to obtain APM.Ace is (in order of introduction of all kinds of components used). Or all the reactive components are always supplied in the total amount used therein when the reaction is carried out at a high temperature, for example 50 ° C.). Applicants have found that all of the above methods form APM.Ace with p.s.d. in the form of dry up to 10 wt. In the citations, it is not disclosed that any effect related to the stability of the dry form of APM.Ace can be found, and the effect related to the stability on the formation of 3A is due to the deformation of the psd and, in particular, at least 10 wt.% Of the particles. It is expected from the beneficial effect of psd having a thickness of 200 mu m or more.

Note that if APM.Ace is prepared according to the contents of ES-A-8604766 (incidentally, APM.Ace preparation is not described), APM.Ace is separated by evaporation from an organic solvent. This first forms an amorphous material, and nothing can be compared with a crystalline product having a p.s.d. of at least 10 wt.% Of the particles being at least 200 μm.

It should be noted, however, that in the scope of European Patent EP-A-0768041 referring to particle size, the patent application mainly establishes the relationship between the desired 'sweetener release' and the secretion effect in the powder mixture. . However, nothing is said about the effect of this effect on the stability of possible production of 3A.

For reference, APM.Ace according to the present invention can be used as a wet solid crystalline product which, upon drying, forms a product having a particle-size distribution with at least 15 wt.%, More preferably at least 25 wt.% Of particles having a particle size of at least 200 μm. Do.

For the preparation in the liquid medium of APM. Ace used in the context of the present invention, a suitable method may be used, in which the psd having at least 10 wt.% Of particles at least 10 wt. The solid APM.Ace with satisfies the psd, which is found to be essential in the specification. Embodiments of the method are generally described in EP-A-0768041. In order to further explain the liquid media and conditions and solid-liquid separation methods that can be used in the process, the content of this patent application also relates to them. The characteristics found for obtaining a wet solid crystalline APM.Ace product which, when dried, yield a product having particles having at least 10 wt.% Of at least 200 μm, will be detailed below.

The inventors have found, in particular, that APM.Ace with improved stability associated with the formation of 3A can be obtained if the following means are taken continuously in the manufacture of APM.Ace:

a) using some or all of the inorganic salt of AceH, preferably AceK, i.e., for the reaction to prepare APM.Ace with stirring in an aqueous medium at a temperature between 40 and 65 ° C, preferably about 50 ° C. Feeding at least 5 wt.%, At least at least 40 wt.% Of the total amount of said salt;

b) subsequently, at the same temperature, with stirring or continuing stirring, added as a molar equivalent to the molar equivalent of the inorganic salt of AceH used in an amount of approximately 2 to 50% APM (a)); The addition not only occurs rapidly but also in small amounts; Usually, about 10-30 wt.% Of the total amount of APM used will be added to this step;

c) subsequently introducing a strong or partial amount of a strong acid, such as an aqueous HCl solution, within 30 minutes at the same temperature and while continuing to stir; The amount used allows the total amount of strong acid added to be 5-10% deficient for small molar deficiency rates, eg APM added to b),

d) in the next step, while continuing to stir at the same temperature, one or part of an additional amount of inorganic salt of AceH is added, if necessary, and an additional amount of APM and strong acid together with a strong acid in the form of a salt of APM; The addition takes place gradually and the total amount of APM supplied is kept constant less than the introduction amount of the inorganic salt of AceH, the substances are added together or above each other equivalent or less, and the addition is the total amount of APM used is AceH Continuing until approximately equivalents to the total supply of inorganic salts of;

e) Gradually introducing the strong acid while continuing to stir at the same temperature until the total amount of APM administered is no longer insufficient.

In the above, in particular:

f) steps c), d) and optionally also e) with pH control during the reaction, wherein the pH measured using a calibrated pH meter at the reaction temperature maintains at least 3 levels as possible; This is done by adjusting the introduction of strong acids at low speeds;

g) the residence time at said temperature from the beginning of adding strong acid to the latter of adding strong acid is at least 1 hour, and

h) During the formation of APM.Ace, the reaction system is continuously stirred so that a viscous slurry that cannot be well stirred during the reaction is formed in an instant, thereby ensuring that there is an agitable slurry throughout.

This prevents the so-called hot-spot from occurring, in which a detectable amount of 3A is formed during the reaction as a result of the locally very high concentration of the strong acid.

After the reaction step has been carried out, the formed APM.Ace can be separated as a wet solid product from the liquid reaction medium at the temperature used. Optionally, the reaction system may be cooled to ambient temperature by first cooling further to a temperature in the order of 5-20 ° C. before the solid APM.Ace formed is separated from the liquid reaction medium as a wet solid crystalline product.

Drying of the separated wet solid crystalline APM.Ace preferably takes place under mild conditions, i.e. below 60 ° C, preferably about 50 ° C, optionally slightly reduced pressure or inert gas. Preferably, APM.Ace is dried to a moisture content of 0.1 wt.% Or less, based on the total weight of the dry product.

The reaction is selected to form APM.Ace, which produces a product having a particle-size distribution with at least 10 wt.% Of the particles at least 200 μm on drying (e.g., during the trans-chlorination process) and then during the drying step. When APM.Ace is prepared according to the conditions and methods described above, the risk of 3A formation is limited to an extreme minimum amount during the synthesis of the dry product as well as during extended heating (48 hours, 80 ° C.).

In certain embodiments of the present invention, APM. Ace, which is usable as a wet solid crystalline product which produces a product having a particle-size distribution with at least 10 wt. One or more steps of washing are carried out, at least the last of which is carried out by a basic aqueous solution having a pH of 8 or more.

In this particular embodiment according to the invention, one or more steps of said washing may be carried out, it being understood that the final washing is in all cases carried out by a basic solution having a pH of at least 8. If the washing operation is carried out in one step and the washing is carried out immediately with the basic solution, particular care should be taken to wash away the inorganic salts present in the product.

As the basic aqueous solution having a pH of 8 or more, a specific solution of an inorganic or organic compound which forms a solution having a pH of 8 or more at the concentration used may be selected. In this patent application, pH means that the pH of the solution was measured at room temperature (20 ° C.) in all cases using a calibrated pH meter. For those skilled in the art, no base is used in the context of the present invention that reacts with APM.Ace in an undesirable manner or leaves undesired contaminants or undesirable odor or taste characteristics in the product obtained after use. Preferably, a base is used which has little or no residue in the recovered APM.Ace.

In the context of the present invention, examples of bases that can be used in basic aqueous solutions are inorganic hydroxides such as alkali hydroxides and alkaline earth hydroxides such as sodium hydroxide, potassium hydroxide, calcium hydroxide and magnesium hydroxide, as well as ammonium hydroxide as well as organic bases, For example sodium benzoate or potassium benzoate and similar bases suitable for use in preparing foodstuffs.

The basic aqueous solution is preferably a solution of sodium hydroxide and / or potassium hydroxide.

Preferably, the basic washing is carried out using an aqueous solution of base having a pH of 8-13, in particular in the range of about 10.5 to about 11.5. If a very high pH is chosen, for example a value above 13.5, then there is a risk that APM in APM.Ace will begin racemizing and / or be applied to an increased degree for undesirable side reactions or diketopiperazine formation, such as ester hydrolysis. have. If the pH of the basic aqueous solution used for washing is selected to be 8 or less, the effect of the washing is very low.

Usually, the temperature of the basic solution used in the washing operation will be 20 ° C. or lower, with a range of 15-5 ° C. being preferred. The washing operation itself is also preferably carried out at the temperatures mentioned above for the basic solution. This prevents unnecessary temperature changes during cleaning. As the temperature at which the washing operation is carried out increases, the quantity of the desired product (APM. Ace) lost through the mother liquor to be separated off will increase. The above quantification of dissolved APM.Ace removed through the mother liquor can be recovered, but it is true that this requires an additional process step.

The time spent for the basic washing operation, ie the residence time of the solid APM. Ace recovered in the presence of basic aqueous solution, is not very important. One skilled in the art can easily determine the optimum conditions for the cleaning operation. Obviously, the risk of decomposition and / or formation of undesirable by-products increases as time goes by for basic cleaning operations. Usually, APM.Ace will be in contact with the basic aqueous solution for at least several seconds, usually up to several minutes, for example 2 to 20 minutes. The time used for the basic washing operation, the time the liquid medium is present in the wet crystal cake is replaced by a basic solution, and as apparent by the person skilled in the art, depends in part on the amount of APM.Ace washed and the equipment used for the above. do.

Conventional washing as well as washing with basic solutions can be carried out using crystal washing methods known to those skilled in the art. In one embodiment, the APM.Ace crystalline obtained upon solid-liquid separation on a horizontal filter cloth optionally adds a basic wash to the (small) layer on top of the crystalline material and continuously fills the filter cloth and filter with it. Overpressure on the filter, or on the same filter cloth with reduced pressure. The filter cloth may also be installed in a centrifuge.

Prior to washing with the basic aqueous solution according to the invention, preferably at least one washing with water is first carried out. This allows not only the amount of basic wash water required for the present invention, but also to limit the formation of by-products as a result of basic washing operations. If desired, the basic washing operation according to the invention can also be repeated one or more times before the APM. Ace is decomposed, by drying by methods known to those skilled in the art to obtain the desired dry product.

The amount of basic wash liquor used in the process according to the invention will usually not be critical. Preferably, at least 10 wt.% (Calculated on dry weight) of the basic aqueous solution relative to the amount of APM.Ace is used. The optimum amount of wash liquor can be simply determined by one skilled in the art depending on how APM.Ace is made and the conditions and equipment under which the basic wash operations are carried out. For example, the lower the residual moisture content of the wet crystalline material, the smaller the amount of basic wash solution that needs to be used.

The invention also relates to dried crystalline APM.Ace having a particle-size distribution with at least 10 wt.% Of the particles being at least 200 μm, in particular at least 15 wt.%, And more preferably at least 25 wt.% Of the particles being 200 And above, and optionally also treated by a basic washing operation before drying. The wet solid crystalline APM.Ace can be dried by known methods, similar to the above. In particular, when APM.Ace is prepared according to the embodiment of EP-0768041, in which the preparation is carried out in an aqueous medium, a product having a particle-size distribution with at least 10 wt. While the above is observed regarding the measurement to obtain APM.Ace as a wet solid crystalline product to form, a dry APM.Ace is obtained, in particular having good thermal stability, very low residual moisture content and very low hygroscopicity, which is dry at high temperatures. The risk of forming 3A upon prolonged storage at is significantly reduced.

According to the present invention there is provided an improved form of APM.Ace with increased stability associated with the ability of 3A to form under conditions involving long exposure to dry form of APM.Ace for 48 hours at high temperature, ie 80 ° C. do. In the improved form of APM.Ace, the 3A content at the exposure remains below the detection limit of 10 ppm by dry weight basis of APM.Ace.

The APM.Ace is characterized in that its acetoacetamide content remains at 10 ppm or less relative to the dry weight of APM.Ace when the APM.Ace is heated in a dry form at 80 ° C. for 48 hours. Other properties of APM.Ace correspond to those of the product obtained in the APM.Ace preparation method used before the present invention. The product is distinguished from the highest technical level only in terms of the risk that 3A is formed.

The invention will now be described with reference to the following examples and comparative examples. The examples do not limit the invention in any way.

All analyzes for 3A were performed using HPLC (High Performance Liquid Chromatography) techniques, in particular gradient elution methods. Injection volume is 250 microliters in all cases; The total run time is 50 minutes at a flow rate of 1.5 ml / min.

Equipment: thermostable controlled column oven set at 20 ° C. (Hewlett Packard HP 1090); Column length 250 mm, inner diameter 4 mm, packed by LiChrospher 100RP-18 (5 micrometer particles; Merk); Variable wavelength detector (Spectra Physics, Spectra 200), UV detection at 300 nm. 10ppm detection limit for 3A (dry weight basis of dry APM.Ace)

Mobile phase: a mobile phase of the following components,

(1) 2 times dilution

(2) Methanol HPLC Grade (Chromasolv; Riedel de Haen 34860)

(3) tetrabutylammonium hydrogen sulfide (TBAHS); Fluka 86875

(4) 0.1 M aqueous potassium hydroxide solution,

Three solvents (A, B, C) having the following composition were prepared.

ingredient Solvent A Solvent B Solvent C (One) 2000 ml 1800 ml 2000 ml (2) 200 ml (3) 6.8 g 6.8 g 6.8 g (4) 5.6 g

The elution gradient used was as follows:

Minutes Solvent A (%) Solvent B (%) Solvent C (%) 0 40 10 50 16 20 30 50 18 50 50 33 50 50 35 40 10 50

pH measurements were performed using a Knick Portamess 752 Calimatic pH meter equipped with ROSS ™ pH electrode 8155SC.

Example I

In a 2-L crystallizer having a shell temperature of 50 ° C., the following was combined by stirring: 466 g demineralized water, 141 g (0.70 moles) AceK, and 65 g (0.21 moles; moisture content 4%) of APM. Then, 33% HCl aqueous solution was added by dropping for 25 minutes until the pH reached 3.5. Subsequently, 5 g of APM was added every 5 minutes (overall 150 g extra, or 0.49 moles), and the pH was adjusted to 3.5 by dropwise addition of additional HCl solution. After all APMs were introduced, a final amount of 33% HCl was introduced to add 77 g total in 33% HCl (0.70 moles). Three hours after the start of the experiment, cooling was started (low temperature holding apparatus 10 ° C). After 3 hours cooling, overall, 716 g of slurry was obtained. The slurry was filtered off in a chilled Buchner tube with a month temperature of 10 ° C., washed twice each time with 180 ml of 10 ° C. demineralized water, and its pH was raised to 11.0 by solid KOH. The moisture content of the collected wet cakes was 19.2 wt.%. The wet cake was dried in a fluid bed at 50 ° C. for 1 hour. At the time of drying the moisture content was less than 0.1 wt.%. 41.6% of the particles were at least 200 μm. Acetoacetamide (3A) could not be verified in this product.

The dried product was maintained at 80 ° C. for 48 hours, after which the 3A content was remeasured. Still no 3A was detected. Even after 13 weeks and 1 year of storage at 60 ° C, 3A was not detected.

Example II

In a 30 L crystallizer with a month at 50 ° C., 10 kg of demineralized water and 3.015 kg of AceK were combined by stirring. After 20 minutes, 1.3 kg of APM (4% moisture content) were added. After 30 minutes, a 33% aqueous HCl solution was introduced. In total, 1.646 kg of aqueous HCl solution had to be added. After 1 hour, 24 wt.% HCl solution was added and the total APM amount was 28.3 wt.%. Then 165 g of APM was added every 5 minutes and the total HCl solution was added. Three hours after the start of the experiment, cooling was started (low temperature holding apparatus 10 ° C). After 2 hours of cooling, the slurry temperature was 11 ° C. The slurry was filtered off in a chilled Büchner tube with a month of 10 ° C. at a portion of 1.75 kg.

Wash two of them with twice 200 mL demineralized water; The other place was first washed with 200 ml of demineralized water and then with 200 ml of demineralized water whose pH was raised to 10.7 by solid KOH. Thereafter, some 750 g were dried in a fluidized bed at 50 ° C. for 1 hour. After the drying, the moisture content was 0.1 wt.% Or less. About 31 wt.% Of the particles were at least 200 μm. Acetoacetamide (3A) could not be detected in some of the above.

Samples of some of the dried product were maintained at 80 ° C. for 48 hours, with the 3A content being remeasured. In either case, 3A could not be detected. Even after 13 weeks and 1 year of storage, 3A was not detected.

Comparative Example A

A 25 L crystallizer having a shell temperature of 20 ° C. was charged with 20 L demineralized water, and 6.03 kg (30 moles) of AceK was added thereto. The shell temperature thermostat was set at 50 ° C. to gradually raise the crystallizer temperature during the experiment. Then, 3,07 kg of APM was added while stirring (2 moles; 4% moisture content) within 2 minutes. During the entire APM addition time, 33% HCl aqueous solution was added at a rate of 35 g / min. After 9 minutes, the reaction mixture was no longer stirred, after which additional 5 kg of water was added. After 10 minutes, 500 g of APM was added. Then 500 g of APM was added every 5 minutes for 20 minutes. As the reaction mixture became thicker again, APM addition was stopped for 15 minutes. Then 500 g of APM was added every 5 minutes for 30 minutes and 630 g of APM was added last. The total amount of APM added was 92.2 kg (30 moles) and the total amount of HCl solution added was 3.3 kg (30 moles). The thermostat was set continuously at 10 ° C. After 3 hours of cooling, the crystallizer temperature was 22.8 ° C. and the slurry was centrifuged at 3 L. Each portion was washed twice with 300 ml of demineralized water at 20 ° C. The moisture content of the collected wet cakes was 5.7%. The wet cake was dried at 50 ° C. in a day dryer at low speed (about 70 rpm) for 3 hours. 12.25 kg of dry APM.Ace was obtained. At the time of drying the moisture content was less than 0.1 wt.%. About 2.8 wt.% Of the particles were 200 μm. Acetoacetamide (3A) could not be detected in the product.

The dry product was maintained at 80 ° C. for 48 hours after which the 3A content was remeasured. At this time the 3A content was 17 ppm.

After storing samples of dry APM.Ace at 40 ° C. for 14 weeks, 3A could not be detected in the product.

After 1 month of storage of dry APM.Ace at 60 ° C., 17 ppm of 3A were found. After 13 weeks storage at 60 ° C., the concentration of 3A increased to 32 ppm.

Comparative Example B

By stirring, 688 g demineralized water, 141 g (0.70 moles) of AceK and 215 g (0.70 moles; 4% moisture content) of APM were combined in a 1-L crystallizer. Subsequently, it heated to 50 degreeC, and 127.7 g of 20% HCl aqueous solution was added dropwise by pipette within 33 minutes. Initially, a slurry that was difficult to stir was formed; After that it became thick. After the HCl solution was added, cooling was started (cold keeping 10 ° C). After cooling for 2 hours, the slurry as a whole was filtered off in a cooled Buchner tube with a 10 ° C. month, and then washed twice with 180 ml of demineralized water at 10 ° C. each time. The moisture content of the collected wet cakes was 34 wt.%. The wet cake was dried in a fluid bed at 50 ° C. for 1 hour. The moisture content at the time of drying was 0.1 wt.% Or less. 8.7 wt.% Of the particles were at least 200 μm.

The dried product was maintained at 80 ° C. for 48 hours, at which time the 3A content was remeasured. 3A could be detected.

Claims (19)

A process for preparing salts of acesulfame acid and aspartame in solid and dry form, which is prepared in a liquid medium, therefrom separated as a wet solid product by solid-liquid separation, and then dried. Salts of acesulfamic acid and aspartame can be used as wet solid crystalline products which, when dried, form a product having a particle-size distribution with at least 10 wt.% Of particles of at least 200 μm. Way. The method of claim 1, Acesulfame acids and salts of aspartame can be used as wet solid crystalline products which, when dried, form a product having a particle-size distribution with at least 15 wt.%, In particular at least 25 wt.%, Of at least 200 μm. Method for preparing salts of palmic acid and aspartame. The method according to claim 1 or 2, Salts of acesulfame and aspartame are: a) Acesulfame acid (AceH) required for the reaction to prepare acesulfame acid and salts of aspartame (APM.Ace) or portions thereof with stirring in an aqueous medium at a temperature between 40 and 65 ° C., preferably about 50 ° C. Supplying the total amount of inorganic salts); b) adding about 2-50% APM, calculated as molar equivalents to molar equivalents of the inorganic salt of AceH supplied in a) above, at the same temperature, and while stirring or continuing stirring; c) slowly adding the strong acid to the reaction system while continuing the same temperature and stirring with a small molar deficit with respect to the APM added in b) in the total amount of the strong acid added; d) At the same temperature and while stirring, above or below the molar equivalent, adding the inorganic salt of AceH and slowly adding the APM and the strong acid, the total amount of APM used is the total supplied of the inorganic salt of AceH Continuously ensuring that the total amount of APM supplied is kept less than the amount of inorganic salt of AceH added until it is approximately equivalent to the amount; e) continuing stirring at the same temperature, slowly adding strong acid until no longer insufficient for the total amount of APM administered; Method for producing a salt of acesulfame acid and aspartame, characterized in that continuously produced by. The method of claim 3, wherein Steps c) and d), and optionally also e), proceeding while measuring the pH during the reaction, wherein the pH is maintained as long as 3 or more as long as possible. The method according to claim 3 or 4, A method for producing salts of acesulfame and aspartame, characterized in that the residence time is at least 1 hour at the temperature from the beginning of the addition of the strong acid to the latter part of the addition of the strong acid. The method according to any one of claims 3 to 5, Wherein the reaction system is stirred in such a way that a stirrable slurry is present through the reaction while forming the salts of acesulfame acid and aspartame. The method according to any one of claims 3 to 6, The salts of acesulfamic acid and aspartame formed are separated from the liquid medium as wet solid crystalline products and are subsequently dried at 60 ° C. or lower, preferably about 50 ° C. The method of claim 7, wherein A salt of acesulfame acid and aspartame is dried to a moisture content of 0.1 wt.% Or less based on the total weight of the dry product. The method according to any one of claims 3 to 8, The product obtained in the form of a liquid medium of the salts of acesulfamic acid and aspartame and separated as a wet solid product from the liquid medium by solid-liquid separation is also subjected to a washing operation in at least one step before drying. At least at the end of the washing operation, the method for producing salts of acesulfame and aspartame, characterized in that the washing with a basic aqueous solution having a pH of 8 or more. The method of claim 9, The basic aqueous solution is a solution of acesulfame acid and aspartame, characterized in that a solution of sodium hydroxide and / or potassium hydroxide. The method according to claim 9 or 10, The basic aqueous solution has a pH of 8-13, in particular in the range from about 10.5 to about 11.5. The method according to any one of claims 9 to 11, A method for producing salts of acesulfame and aspartame, characterized in that the temperature of the basic aqueous solution is at most 20 ° C, in particular within the range of 5-15 ° C. The method according to any one of claims 9 to 12, The washing operation is a process for preparing salts of acesulfame and aspartame, characterized in that it is carried out at a temperature of less than 20 ℃ and in particular in the range of 5-15 ℃. The method according to any one of claims 9 to 13, A salt of acesulfame acid and aspartame is contacted with basic aqueous solution for at least several seconds, preferably 2 to 20 minutes. The method according to any one of claims 9 to 14, A method for producing salts of acesulfame and aspartame, wherein before washing with a basic aqueous solution, washing with at least water is carried out. The method according to any one of claims 9 to 15, A method for producing salts of acesulfame and aspartame, characterized in that at least 10 wt.% Of the basic aqueous solution is used relative to the amount (as dry weight basis) of salts of aspartame and acesulfame. For salts of acesulfamic acid and aspartame which have increased stability, Salt of acesulfame acid and aspartame, characterized in that the acetoacetamide content is less than 10 ppm by dry weight of salt when the salt is heated for 48 hours at a temperature of 80 ° C. Salts of acesulfame acid and aspartame having a particle-size distribution with at least 10 wt.% Of the particles in dry form of at least 200 μm. The method of claim 18, Salts of acesulfame and aspartame, characterized in that in dry form at least 15 wt.%, In particular at least 25 wt.%, Have a particle-size distribution of at least 200 μm.