JPH0834795A - Method of crystallizing aspartame - Google Patents

Abstract

PURPOSE: To provide a process for the crystallization of aspartame by neutralizing an aqueous solution of aspartame having a specific acidic pH value with a base, homogenizing the product by agitation, stopping the mechanical agitation when the crystallization becomes visible and depositing large crystal of the subject compound having low filtration resistance without cooling the system for a long period.

CONSTITUTION: Aspartame is crystallized from an aqueous solution of aspartame having a pH of <3 by the neutralization with a base and he homogenization by forced convention flow. Aspartame crystal having relatively large crystal size and low filtration resistance can be produced dispensing with a prolonged cooling step by neutralizing an aqueous solution of aspartame having a pH of <3 and an aspartame concentration of 1.5-20 wt.% with an aqueous solution of sodium hydroxide, etc., under vigorous agitation at 5-80°C to effect the neutralization and homogenization of the aspartame solution under a condition to get a homogeneous aqueous solution and a pH of >3 after neutralization and, after the continuance of the homogenization for ≤10 sec, depositing the crystal for 2 min to 2 hr without performing the mechanical agitation of the solution at or after the time when the crystallization reaches a visually sensible state.

COPYRIGHT: (C)1996,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for crystallizing aspartame from an aqueous solution of aspartame having a pH of less than 3 by neutralization with a base and homogenization by forced convection.

Aspartame is a sweetener that is widely used in low-calorie products such as soft drinks.

[0003]

PRIOR ART Aspartame is mainly crystallized after synthesis from an aqueous solution or, if desired, containing up to 20% by weight of methanol or ethanol. In various commercial aspartame manufacturing processes, first of all, it is crystallized as the hydrochloride salt of aspartame. This salt is, for example, as described in US-4,618,695,
The acidic solution is neutralized and, if necessary, recrystallized by further cooling the solution. This method is carried out in suspension solution, for example as described in US-4,778,916, or for example in US-4,67.
7, 222 and US-4,656,304, by preparing a homogeneous solution at elevated temperature with stirring, neutralizing and cooling. Neutralization is carried out, for example, with EP-
It is carried out by dropping an alkali into the solution as described in A-187.530 and US-4,918,216.

The solubility of aspartame in water is relatively low, so that the crystallization yield per liter of solution is relatively low. For example, in order to crystallize 40 g of aspartame, it is necessary to cool 1 liter of an aqueous solution containing 4.8 wt% aspartame from 60 ° C to 5 ° C. In this operation, aspartame is preferably produced in a stirred crystallization tank, since a relatively large amount of aqueous solution must be cooled. The stirring type cooling crystallization tank is excellent in that heat can be removed relatively efficiently.

However, stirring crystallization of aspartame has the disadvantage that the crystals obtained have a relatively high filtration resistivity. This means that it is generally quite difficult to filter the aspartame slurry after crystallization.

[0006] EP-A-091.787 proposes that aspartame crystallizes by cooling while standing (without stirring). Originally, larger crystals can be obtained by this method than by stirring crystallization, but the cooling efficiency in the unstirred solution is relatively low, and a relatively large heat exchange area is required.
Crystallization requires a relatively long time.

[0007]

SUMMARY OF THE INVENTION An object of the present invention is to provide a method for crystallization of aspartame in which a relatively large crystal having a low specific resistance can be obtained and a long cooling step under stationary conditions is unnecessary. To do.

[0008]

According to the present invention, the pH
In a method of crystallizing aspartame from an aspartame aqueous solution having a ratio of less than 3 by neutralization with a base and homogenization by forced convection, the solution after neutralization is substantially uniform and the pH is higher than 3. This is achieved by the fact that the aspartame solution is neutralized and homogenized and that no mechanical stirring of the solution takes place at least after the moment when crystallization is visually perceptible. The mechanical stirring here means that forced convection is caused in the system by mechanical means such as a stirrer or a pump. In the sense of the present invention,
Stopping these mechanical means means no forced convection thereafter.

The pH of the solution depends on the Krick Portam.
It means the pH of each solution measured at each temperature using an ess 752 type pH meter, and its actual pH value is the pH measured at each temperature automatically calculated as p at standard temperature 20 ° C.
Corrected to H. In the present invention, when pH is referred to, the latter pH at standard temperature of 20 ° C. is always used.

The pH of the solution before neutralization is less than 3, but in principle higher than 0.5, preferably higher than 1 and more preferably higher than 1.5. An excessively low pH promotes the decomposition of aspartame, which is not preferable. Maximum solubility is at pH 2.3. Therefore, a pH below 2.9 is preferred, and even below 2.5. The pH is only important for the solubility of aspartame. If the pH is too high, the solubility of aspartame will be low and (undesirable) crystallization may occur.

Very suitable acids for bringing the pH below 3 are hydrochloric acid, sulfuric acid, phosphoric acid or nitric acid. Of these, use of hydrochloric acid or sulfuric acid is preferable, and use of hydrochloric acid is particularly preferable. The acid concentration is not critical, but for economic reasons it will be above 1N. Generally, a saturated solution or a solution with a concentration between 5 and 12 N will be chosen. However, it is also possible to acidify the solution by passing hydrogen chloride gas through it. It is also possible to start from aspartame salts such as, for example, hydrochlorides, sulphates or phosphates.

The amount of aspartame in the solution before crystallization is in principle 1.5 to 20% by weight. It is preferred that the amount of aspartame is greater than 3% by weight. Weight% aspartame herein means the amount of aspartame calculated as free aspartame. The solubility of aspartame in aspartame salts or acidic solvents is substantially greater than the solubility of neutralized aspartame, and one skilled in the art can readily determine the concentration of aspartame at which crystallization does not occur prior to neutralization.

Preferably, this concentration is 1% by weight after neutralization.
It is selected to have a greater supersaturation and even greater than 1.5% by weight. However, as a rule, supersaturations below 15% by weight, in particular below 8% by weight, are selected. Here, supersaturation is expressed as absolute supersaturation in% by weight aspartame. Excessive supersaturation produces small crystals with poor filterability. However, large supersaturation is important because it gives a high yield per volume.

The aqueous solution may contain small amounts, ie up to 25% by weight, of lower alcohols having 1 to 4 carbon atoms, eg ethanol or methanol.

The aspartame solution having a pH below 3 is then brought to a pH above 3 using a base. It is preferable to obtain a pH of more than 4 and less than 8 with the amount of added base. In particular, the amount of addition thereof is particularly preferably an amount of pH 4 to 7, and more preferably 4 to 6.

The base used is preferably an aqueous alkali solution, particularly preferably an aqueous solution of sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, ammonium hydroxide or ammonium carbonate. In principle, 0.1
It is used at a concentration higher than N, preferably higher than 0.2N. The low concentration of the base in the alkaline aqueous solution is advantageous when the person skilled in the art mixes approximately equal amounts of the two aqueous solutions. However, for economic reasons, the amount of water to be filtered is reduced and a high yield is obtained, so 1N
Higher concentrations or saturated solutions of base are often used. Preference is given to using an aqueous solution of sodium hydroxide or ammonium hydroxide. However, it is also possible to use a base such as sodium hydroxide, which dissolves very quickly by mixing the aspartame solution to be neutralized, as a very finely divided solid. In such cases, a homogeneous solution should be made as fast as possible to avoid undesired decomposition to diketopiperazine at high pH. It is also possible to use gaseous ammonia gas as the base.

In the process according to the invention, the base is added to the aspartame solution to be neutralized within a very short time. The forced convection required to quickly mix the base with the aspartame solution is within a short time such that there is at least 1 second between the time when the solution is no longer exposed to forced convection and the time when visible crystallization begins. Must be implemented. This interval is preferably at least 3 seconds, particularly preferably 4 seconds.

Such a homogenization method within the scope of the present invention is such that the means for introducing forced convection is stopped at least 1 second, preferably at least 3 seconds before the start of its crystallization, or
Or, it means to handle the solution so that substantially no further forced convection occurs. The latter applies in particular to continuous crystallization, such as plug-flow continuous crystallization through a pipe. After stopping the agitation, convection still occurs for a while even after the mechanical means is stopped until the solution is completely left at rest. However, this convection is not substantially important to the present invention and is not considered forced convection.

The moment of onset of visible crystallization depends on many factors such as the degree of supersaturation and the temperature of the solution. For example, 4 wt% supersaturation has less available time for mixing than 2 wt% supersaturation.

The experiment according to the present invention can be carried out in a glass container, and the start of crystallization can be easily visually confirmed in the glass container. It is also possible to use light scattering techniques such as laser light to confirm the onset of crystallization. The start time is defined as the time from the addition of all the base until the first crystallization can be visually confirmed. This start time is surprisingly long and indicates the degree of supersaturation. The presence of other compositions in the solution, such as additives such as salts and impurities, affects its onset time.

Preferably, the starting time is at least 10 seconds by selecting the temperature and the degree of supersaturation. This facilitates neutralization and homogenization of the acidic aspartame solution and subsequent crystallization from the solution without forced convection.

If desired, the crystallization start time can be prolonged by increasing the temperature of the aspartame solution. For example, in an aspartame solution having a supersaturation concentration of 3% by weight at 60 ° C., the initiation of crystallization is visually confirmed after 60 to 120 seconds.

The mixing of aspartame and base is preferably carried out in a static mixer, the mixing solution being pumped to the mixer. Other devices for rapidly mixing two liquids (or one liquid and one solid or gas that dissolves rapidly in that liquid) can use devices known to those skilled in the art. The mixing may be carried out as a continuous or discontinuous process.

The homogenization of the aspartame solution for neutralization (by forced convection) may not be visible for 120 seconds, although it is particularly important that it completes before crystallization occurs. It is preferable that the homogenization is not performed for 10 seconds or longer, more desirably 5 seconds or longer.

After mixing, directly add the neutralized aspartame aqueous solution into a container, if desired, into a container provided with a partition wall as soon as possible to reduce convection of the solution,
The aspartame is crystallized from the solution under static conditions.

When the present invention is used, the crystallization is visually completed very quickly (at a given temperature), so that the crystallization solution is crystallized in a tubular vessel pumped at a very slow rate. It is also possible to carry out continuously.

As mentioned above, various methods of obtaining aspartame hydrochloride (US-4,618,695, US-4,7).
78,916, US-4,677,222 and EP-1.
87, 530) are known. The crystallization method according to the present invention is very suitable for quickly crystallizing such a salt to obtain a very pure aspartame or a slurry having good filterability.

However, for example, US-3,78
It is also possible to prepare aspartame as a neutral compound from precursors having protective groups, as described in 6,039 and US-4,282,721.

After acidifying the pH to less than 3, it is possible to cool the resulting solution as a solution very efficiently, and the crystallization method of the present invention can be applied. The method of the present invention is very advantageous for the obtained aspartame. As this first preferred embodiment,
A neutral aspartame solution containing more than 1.5% by weight, preferably more than 3% by weight of aspartame,
At a temperature above 50 ° C., preferably between 50 ° C. and 80 ° C., particularly preferably between 55 ° C. and 70 ° C.
Bring H to less than 3 and cool the solution under forced convection by at least 10 ° C. In the operation until the cooling,
The concentration, temperature and pH are chosen so that the aspartame does not crystallize before cooling. Preferably, the solution is cooled at 30 ° C, especially at 40 ° C.

However, at high concentrations of aspartame, cooling temperatures may be small, for example cooling at 20 ° C may be sufficient. As with the specific example of acidifying this neutral solution, it is of course possible to dissolve aspartame in already acidic water, preferably warm water. Thus, by using the crystallization method of the present invention, it is possible to obtain very highly pure aspartame crystals from aspartame crystals which still contain undesirably large amounts of impurities.

Thereafter, the cooled solution is brought to a pH of 3 or higher by using a base under forced convection. Subsequently, before the start of crystallization, the means for producing the forced convection is stopped, and aspartame is crystallized under static conditions.

The warm solution is cooled in a known manner. The use of once-through heat exchangers in which heat is removed efficiently is preferred.

The temperature in the cooled acidic solution is, in principle, 40 ° C. or lower, but when starting from an acidic solution having a high temperature and a high concentration, a temperature of 70 ° C. or lower may be used. Further cooling the solution to 5 ° C is not economically advantageous. It is preferred to cool the solution to 5-35 ° C.
Low temperatures have the advantage of hindering the growth of microorganisms. However, high temperatures have the advantage of increasing the time before crystallization begins. Unexpectedly, it was revealed that at high temperatures, crystals with good filterability were obtained in a highly supersaturated state.

As a further preferred embodiment of the present invention, aspartame hydrochloride is dissolved. Such a solution is about 1.
It has a pH of 5-1.8. If desired, the solution may have a different pH between 1 and 3. It is advantageous to dissolve the aspartame salt at a temperature between 20 and 80 ° C. (to increase the dissolution rate) and then cool the acidic solution (to improve the crystallization efficiency).

Usually, 2 minutes to 2 hours, preferably 5 to 3
After crystallization for 0 minutes, if desired, a pseudo-solid phase is mechanically disentangled, then the resulting slurry is combined with a solid-liquid separator, such as a centrifuge or belt filter. Lead to. However, it is also possible to further cool the slurry in the crystallizer under forced convection. This method is particularly suitable when the aspartame solution is neutralized at a temperature of 15 ° C. or higher, especially 25-40 ° C. For carrying out this last stirred crystallization step, the aqueous crystal slurry is kept at 25 ° C. or lower, preferably 20 ° C. or lower, particularly preferably 5 ° C.
Cool to a temperature of ~ 15 ° C.

After the crystallization is complete, the crystals are separated from the water as described above, for example by filtration or centrifugation. The resulting wet crystal mass is preferably washed with cold deionized water. The cake obtained after filtration and washing usually consists of aspartame with a water content of 25 to 50% by weight. The wet aspartame cake is then dried in a further known manner to a water content of 1 to 6% by weight.

The present invention is further described in connection with the non-limiting examples below.

[0038]

EXAMPLES In this example, the specific resistance R (m / kg)
And the particle size of the slurry (represented by the characteristic diameter, D _ch (μm)) is calculated as follows.

The filtration test was carried out using a filter having a surface area of 19.64 cm ² . The filtrate was placed in a container and its weight was continuously measured by a recorder. The differential pressure for slurry filtration was obtained by applying a controlled pressure over the slurry.

The specific resistance was calculated from the following formula (I).

T / V (sec / m ³ ) = (R · η · C / 2 · ΔP · A ² ) · V + (Rm · η / ΔP · A) (I) t = filtration time (sec) V = Filtrate volume (m ³ ) R = specific resistance (m / kg) ^* η = kinematic viscosity of the filtrate (Pa · sec) ΔP = pressure difference between filter and cake C = per unit volume of the obtained filtrate Weight of precipitated crystals (kg / m ³ ) Rm = filter resistance (1 / m) A = filter surface area ^* resistivity of cake during slurry filtration Characteristic diameter D _ch is calculated from the following formula (II).

D _ch = {(V ² · 360 · η · C) / (t · A ² · ΔP)} ^1/2 (II) where each symbol has the above-mentioned meaning, and ΔP is 10 ⁵ Pa
Is.

Stirring crystallization of aspartame was 6 × 10 ¹⁰
It gives a specific resistance (R) greater than m / kg and a characteristic diameter D _ch of about 3 μm. When the crystallization method of the present invention is used, crystals having an R of 5 × 10 ⁸ to 4 × 10 ¹⁰ m / kg and a D _{ch of 4} to 20 μm are very advantageously obtained by rapid crystallization.

Preferably, the crystallization method of the present invention is carried out in a simple manner for a person skilled in the art and has a specific resistance of less than 1 × 10 ¹⁰ m / kg, in particular 1 × 10 ⁸ to 8
An aspartame slurry of × 10 ⁹ m / kg is obtained. The characteristic diameter is preferably larger than 5 μm, particularly preferably in the range of 7 to 25 μm.

Examples 1-7 3.9 from 1 liter of water at 60 ° C. and aspartame in a 1.75 liter glass container equipped with stirrer and baffle.
A wt% aspartame solution was prepared. In each example, after cooling to the temperature shown in Table 1, a calculated amount of 37 wt% hydrochloric acid solution was constantly metered into 1 liter of the above solution so that a supersaturated solution was obtained.

The acidic aspartame solution was then neutralized with sufficient agitation (300 rpm) in each case with a precalculated amount of 37% by weight NaOH. The solution was left for 5 seconds (theoretical mixing time required was 3 seconds).
Stir and then stop the stirrer. After that, the start of crystallization was visually confirmed within 1 to 10 seconds. After 15 minutes, the slurry was homogenized for 15 minutes under stirring at a rotation speed of 300 rpm. Then, the filtration characteristics of the obtained slurry were measured. Table 1 shows the results.

[0047]

[Table 1]

Comparative Example 1 and Examples 8 to 13 Table 2 shows the measurement results.

[0049]

[Table 2]

The experiment shown in Table 2 was carried out in the same manner as in Examples 1-7.

In Comparative Example 1, the stirrer was not stopped. The stirrer continued to run for 0.5 hours.

In Example 8, the stirrer was stopped after 2 seconds.
Despite the required mixing time of 3 seconds, the solution was sufficiently homogeneous and gave good results.

In Example 11, the slurry obtained at 30 ° C. was further cooled under forced convection. This table shows the filtration characteristics of the finally obtained slurry, which was very easy to filter.

The tests show that crystallization at temperatures above 25 ° C. readily yields slurries with excellent filtration properties.

[0055]

EFFECTS OF THE INVENTION By using the crystallization method of the present invention, relatively large crystals having low filtration resistance can be obtained, and a long cooling step under standing is unnecessary.

Claims (23)

[Claims] 1. A method of crystallizing aspartame from an aspartame aqueous solution having a pH of less than 3 by neutralization with a base and homogenization by forced convection, wherein the neutralized solution has a substantially uniform pH. Of aspartame is characterized in that the aspartame solution is neutralized and homogenized so as to be higher than 3, and at the latest, mechanical stirring of the solution is not carried out after the moment when crystallization is visually detected. Method. 2. The crystallization method of aspartame according to claim 1, wherein the aspartame solution to be neutralized has a pH higher than 0.5. Method. 3. The method for crystallizing aspartame according to claim 1, wherein the amount of aspartame in the solution is in the range of 1.5 to 20% by weight. A method for crystallization of aspartame. 4. The method for crystallization of aspartame according to claim 1, wherein the amount of aspartame in the solution is such that the absolute supersaturation after neutralization is 1 to 15% by weight. A method for crystallization of aspartame, characterized in that: 5. The crystallization method of aspartame according to claim 4, wherein the amount of aspartame is selected so that the absolute supersaturation after neutralization is 1-8% by weight. A method for crystallization of aspartame. 6. The method for crystallization of aspartame according to claim 1, wherein the aspartame solution having a pH of less than 3 is neutralized with an alkaline aqueous solution. Aspartame crystallization method. 7. The crystallization method of aspartame according to claim 6, wherein the aqueous alkali solution used is an aqueous solution of sodium hydroxide or ammonium hydroxide. Method. 8. The method for crystallization of aspartame according to any one of claims 1 to 7, wherein the solution is forcibly convected at least 3 seconds before the crystallization is visually detected. A method for crystallization of aspartame, characterized in that it is not exposed to water. 9. A method for crystallizing aspartame according to claim 1, wherein the aspartame aqueous solution having a pH of less than 3 has a temperature between 5 ° C. and 80 ° C. And crystallization method of aspartame. 10. The aspartame crystallization method according to any one of claims 1 to 9, wherein an aspartame solution having a concentration higher than 1.5% by weight is used for preparing an aqueous solution having a pH of less than 3. So that a certain amount of aspartame is dissolved in water at a temperature of 50 ° C. or higher, the pH of the water is adjusted to less than 3 with an acid before, during or after the dissolution of the aspartame, and then at least under forced convection A method for crystallization of aspartame, which comprises cooling at 10 ° C. 11. The method of crystallization of aspartame according to claim 10, wherein the neutral aspartame solution is brought to a pH of less than 3 in the temperature range of 50 to 80 ° C. Crystallization method. 12. The method for crystallization of aspartame according to claim 10, wherein the solution is 7
A method for crystallization of aspartame, which comprises cooling to 0 ° C. or lower. 13. A method for crystallization of aspartame according to any one of claims 10 to 12, characterized in that the solution is cooled to a temperature of 5 to 35 ° C. . 14. The method for crystallization of aspartame according to claim 10, wherein the solution is cooled through a once-through heat exchanger. 15. The crystallization method for aspartame according to claim 10, wherein the neutral aspartame solution is adjusted to a pH of less than 3 with an aqueous solution of hydrochloric acid or sulfuric acid. Aspartame crystallization method. 16. A method for crystallizing aspartame as claimed in any one of claims 1 to 9 wherein an aqueous solution having a pH of less than 3 is prepared by dissolving aspartame hydrochloride in water, if desired. A method for crystallization of aspartame, characterized in that the pH is varied from 1 to 3 when the hydrochloride is dissolved. 17. The method for crystallization of aspartame according to claim 16, wherein aspartame hydrochloride is 20
A method for crystallization of aspartame, characterized in that an aqueous solution having a pH of less than 3 is prepared by dissolving in water at a temperature of ˜70 ° C. and then cooling the solution. 18. A method for crystallization of aspartame according to any one of claims 1 to 17, characterized in that the homogenization lasts up to 10 seconds. 19. The method for crystallization of aspartame according to claim 18, wherein the homogenization lasts up to 5 seconds. 20. The method for crystallization of aspartame according to claim 1, wherein the neutralized and homogenized solution is used for 2 minutes to 2 hours without forced convection. , A method for crystallizing aspartame, which comprises crystallizing aspartame. 21. The method for crystallization of aspartame according to any one of claims 1 to 20, wherein aspartame is crystallized from a neutralized and homogenized solution at a temperature of 15 ° C. or higher to obtain a product. A method for crystallization of aspartame, characterized in that the obtained slurry is further cooled in a crystallization tank under forced convection. 22. A method for crystallizing aspartame according to any one of claims 1 to 21, wherein the obtained crystals are separated from the mother liquor and washed to a water content of between 1 and 6%. A method for crystallization of aspartame, which comprises drying to dryness. 23. A method for crystallizing aspartame as substantially described in the description and examples.