DE1951231A1 - Process for increasing the optical purity of optically impure lysine monohydrochloride - Google Patents

Description

Code 2115 1 Q Γ Λ 'J O <|

Patent Attorneys 8 MO η eh. Η 2, Bräuhausstraß «4 / IH

STAMICARBON N.V ,, HEERLEN (the Netherlands)

Process for increasing the optical purity of optically impure lysine monohydrochloride

The invention relates to a method for increasing optical purity of optically impure lysine monohydrochloride by removing from an aqueous Solution of optically impure lysine monohydrochloride DL-lysine monohydrochloride by means of a crystallization precipitates.

The mother liquor, which is used in the implementation of this i.a. from the British Patent 963.265 known method remains, then contains optically active lysine monohydrochloride with a higher optical purity than that of the original optically impure lysine monohydrochloride. If necessary, can be made from of the remaining mother liquor the optically active lysine monohydrochloride with increased optical purity can be obtained in solid form, e.g. by means of spray drying or crystallization of the mother liquor. ,

In the above-mentioned British patent, this process is proposed for the production of L-lysine monohydrochloride with an optical purity of over 99% (the same naturally also applies to D-lysine monohydrochloride). For this purpose, L-lysine monohydrochloride with an optical purity of 80-99 % is separated from DL-lysine monohydrochloride by means of crystallization from an aqueous solution which, in addition to the optically impure L-lysine monohydrochloride, contains such an amount of water that it becomes optically pure at 20 C L-lysine monohydrochloride and the water present can form a saturated or almost saturated solution. At 20 +0.05 G, according to the above-mentioned British patent specification, one of the two should exist in the ternary system consisting of L-lysine monohydrochloride, DL-lysine monohydrochloride and water

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Salts form a saturated liquid phase which contains 38.1% by weight of L-lysine monohyurochloride with an optical purity of 99.2 % (98.4% L and 1.6% DL).

In contrast to what you based on this value of the optical Would expect purity of this liquid phase in the ternary system, it now shows that the optical purity of the L-lysine monohydrochloride in the after deposition of the remaining mother liquor of the DL-lysine monohydrochloride which crystallized out at 20 C is always below 99.2%. At first glance, one tends to recognize this fact due to the fact that the equilibrium, which is actually very sluggishly, has not been reached. More accurate balance measurements in the mentioned ternary system at 20 C surprisingly showed that the relevant optical purity is not 99.2% but only 98.0%. In the case of spray drying the mother liquor, which crystallized out at 20 C after the separation DL-lysine monohydrochloride remains, a maximum optical purity of 98.0% can be expected. The fact that according to the examples mentioned British patent ultimately L-lysine monohydrochloride with higher optical Purity than 98% is also entirely due to the fact that the mother liquor in question not by spray drying but by a crystallization process is worked up. When L-lysine monohydrochloride crystallizes out of the mother liquor, the remaining DL-lysine monohydrο ~ Most of the chloride is still metastable in solution.

Surprisingly, it has now been found that when using a crystallization temperature above 20 C and adapting the water consumption to this higher crystallization temperature after precipitation of the crystallized DL-lysine monohydrochloride, a mother liquor is obtained which contains optically active • lysine monohydrochloride, the optical purity of which is higher the more - all other things being equal - the applied crystallization temperature exceeds 20 ° C. When using a crystallization temperature ^{of 30 °} C., an improvement in the optical purity can already be achieved in practice. Precise equilibrium measurements in the aforementioned ternary system show that, for example, at 40 ^° C. an optical purity of the liquid phase in question of 98.4% and, for example, at 60 ° C., an optical purity of 98.7 % can be achieved. Use of a crystallization temperature above 60 C is less interesting in practice , because a highly concentrated solution then has to be used.

It was also found that the amount of water which is in the solution, from which the DL-lysine monohydrochloride is crystallized, may be present, far.

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is less critical than is considered necessary in the known method. The preferred amount of water is between 7% more and 7% less water than corresponds to the amount of water that is required with the present optically pure lysine monohydrochloride to form a saturated solution at the crystallization temperature. It is also possible to improve the optical purity of optically active lysine monohydrochloride with an optical purity below 80% can be increased even further.

The invention therefore provides a method for increasing the optical Purity of optically impure lysine monohydrochloride by removing from an aqueous Solution of the optically impure lysine monohydrochloride DL-lysine monohydrochloride precipitated by means of crystallization and, if necessary, the optically active lysine monohydrochloride dissolved in the remaining mother liquor secreted in solid form;

This process is characterized in that the DL-lysine monohydrochloride crystallizes out is made from the aqueous solution at a temperature of 30 to GO C. The method according to the invention is preferably used a crystallization temperature between 35 and 55 C. In comparison to the use of a crystallization temperature of 20 C with the inventive The process has the advantage that a higher optical purity is always obtained, which means that L-lysine monohydrochloride is used for the of great importance for human food and for pharmaceutical purposes. at the processing of the remaining mother liquor by means of spray drying needs this mother liquor is also heated less strongly in the process according to the invention than when using a crystallization temperature of 20 C.

When implementing the method according to the invention, only then at a certain crystallization temperature the maximum possible optical Purity can be achieved, even if that belonging to the crystallization temperature Equilibrium is present. Even if the equilibrium position - its setting, which takes some time, is accelerated by seed crystals can - is not achieved, a higher optical purity can always be achieved in the process according to the invention, which exceeds the optical purity, when using a crystallization temperature of 20 C in the corresponding non-equilibrium position can be obtained.

The process according to the invention is explained in more detail in the following examples explained without wanting to limit the invention.

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Example 1 ■

376.6 g of an aqueous solution containing 52.4% by weight of L-lysine moriohydrochloride with an optical purity of 92.4% (the amount of water corresponds to the amount required for this, with the I.-lysine monohydrochloride present to be able to form a solution that is just saturated at 40 ° C.) are cooled from 90 ° C. to 50 ° C. and at 50 ° C. within one hour while stirring inoculated with 0.25 g of DL-lysine monohydrochloride crystals. Then under Stirring for a further hour, cooled down to 40 ° C. At this temperature. the stirring is continued for an hour, whereupon the crystallized Mass is filtered off. This gives 343 g of mother liquor which contains 48.2% by weight of L-lysine monohydrochloride with a specific rotation of:

^a ID ° ^{= + 25} ' ⁹ ° ^{(C = 10; 6 n}

which corresponds to an optical purity of 97.8% (the optical purity of the filtered crystals is 63.7%). -

The mother liquor is then evaporated to a weight of 304.8 g, cooled to 15 C and crystallized at this temperature. After Filtration forms 111.4 g of crystals, which consist of 83.8% by weight of lysine monohydrochloride exist with a specific rotation of

α j? ⁰ = + 26.6 ° (C = 10; 6 η HCl) which corresponds to an optical purity of 99.1%.

Comparative example

455.9 g aqueous solution, which 43.3 wt.% L-lysine monohydrochloride with an optical purity of 92.4% (the amount of water corresponds to that Amount, which together with the L-lysine monohydrochloride present to form a solution of 39.4% by weight which is just saturated at 20 C is required) and is obtained by evaporation of a solution of lower concentration, are cooled from 50 G to 30 ° C. within one hour with stirring. At this temperature, the solution is mixed with 0.25 g of DL-lysine monohydrochloride crystals. vaccinates. The mixture is then cooled for a further hour, with stirring, until dxe The temperature of the solution has dropped to 20 C. At this temperature noel Stirred for one hour, after which the mass which has crystallized out is filtered off.

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429.3 g of mother liquor are formed, which contains 40.1% by weight of L-lysine monohydrochloride contains with a specific rotation of:

α | p ° = + 25.5 ° (C = 10; 6 η HCl)

which corresponds to an optical purity of 97.0% (the optical purity of the filtered crystals is 62.0%).

By evaporation of the mother liquor up to a weight of 316 g and Working up this amount in the manner described in Example 1 falls 127.8 g Crystals consisting of 83.9% by weight lysine monohydrochloride with a specific Rotation of

| aj ^ ° = + 26.4 ° (C = 10; 6 η HCl) corresponding to an optical purity of 98.7%.

Example 2

589.4 g of an aqueous solution which contains 42.1% by weight of L-lysine monohydrochloride, whose optical purity is 78.0%, becomes a weight evaporated from 411.7 g. The amount of water present then exceeds that amount which, together with the amount of L-lysine monohydrochloride, is used Formation of a solution just saturated at 30 C is necessary to 10 g. The evaporated solution is cooled to 50 ° C. with stirring, which means Temperature, crystallization occurs even without inoculation. The mixture is then cooled for one hour, with stirring, until the temperature is 30 C, after which the stirring treatment is continued for 3 hours at this temperature. After the crystallized crystals have been filtered off, 279.5 g of mother liquor are formed with 43.1 wt.% L-lysine monohydrochloride, its specific rotation

* Id ° * ^{+ 26 | 1} ° ^{cc = 10} ' ^{6 n HC1)}

is, which corresponds to an optical purity of 98.2%.

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Example 3

343.8 g of an aqueous solution containing 56.6% by weight of L-lysine monohydrochloride with an optical purity of 95.0% and contains 7.8 g of water are less present than, together with the L-lysine monohydrochloride present, is required to form a solution saturated at 45 ° C. 70 ° C inoculated with 0.55 g of DL-lysine monohydrochloride crystals. Then will cooled to 45 ° C. within 2 hours with stirring. At this temperature will stirring continued for a further 2 hours, after which the crystallized mass was filtered off will.

^ 311.8 g of mother liquor are formed, which contains 52.8% by weight of L-lysine monohydrochloride with a specific rotation of

YesI ^ ⁰ = + 26.2 ° (C = 10; 6 η HCl)

corresponding to an optical purity of 98.4%, by spray drying the ' Mother liquor is L-lysine monohydrochloride with the same opt. Purity in solid Maintain shape.

Example 4 , -

812.2 g of an aqueous solution with 34.0% by weight of L-lysine monohydrochloride, the optical purity of which is 97.0% becomes a weight at about 100.degree evaporated from 494.7 g and then at 60 ° C. for one hour ■ cooled down. At this temperature, DL-lysine monohydrochloride crystals are inoculated. The temperature is then increased to 50 ° C within an hour while stirring. cools. After stirring for a further hour at 50 ° C., the mass is filtered off.

479.1 g of mother liquor are formed, which contains 54.6% by weight of L-lysine monohydrochloride contains with a specific rotation of:

I ^ ⁰ ■ + 26.2 ° (C = 10 .; 6 η HCl)

corresponding to an optical purity of 98.4%. By working up this mother liquor L-lysine monohydrochloride is obtained by means of crystallization, almost completely is optically pure.

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Claims (2)

PATENT CLAIMS 1. A method for increasing the optical purity of optically impure lysine monohydrochloride by separating DL-lysine monohydrochloride from an aqueous solution of the optically impure lysine monohydrochloride by means of crystallization and optionally separating the optically active lysine monohydrochloride dissolved in the remaining mother liquor in solid form, characterized in that the DL-lysine monohydrochloride is crystallized out of the aqueous solution at a temperature between 30 and 60 ° C. 2. The method according to claim 1, characterized in that the deposition of the DL-lysine monohydrochloride is carried out at a temperature between 35 and 55 · C. 00 9816/1838