Method for Obtaining Crystalline L-Alanine

Abstract

The present invention relates to a method for obtaining crystalline L-alanine from an aqueous solution of L-alanine, in particular from an aqueous solution of L-alanine, which is obtained from a fermentation process.

Claims

1. A method for obtaining crystalline L-alanine from an aqueous solution of L-alanine containing at least 100 ppm, based on L-alanine, of one or more α-amino acids different from L-alanine, comprising a) providing an aqueous solution of L-alanine containing at least 100 ppm, based on L-alanine, of one or more α-amino acids different from L-alanine; b) subjecting the solution of L-alanine to a crystallization by inducing conditions of a controlled supersaturation in a manner that a ratio c:c* of a concentration c of dissolved L-alanine to an equilibrium solubility c* of L-alanine under the conditions of controlled supersaturation is from >1:1 to 1.5:1, thereby affecting the crystallization of L-alanine; and c) separating crystalline L-alanine from a mother liquor. wherein the aqueous solution of L-alanine is fed to a continuously operated crystallization apparatus, which contains an aqueous suspension of L-alanine crystals.

2. The method of claim 1, where the concentration of dissolved L-alanine under the conditions of supersaturation is from 150 to 400 g/L.

3. The method of claim 1, where the controlled supersaturation is induced at a temperature of at least 30° C.

4. The method of claim 1, where the controlled supersaturation is induced by removing water and/or by cooling.

5. The method of claim 4, where the water is removed by evaporation.

6. The method of claim 1, where step b) comprises b1) continuously feeding the aqueous solution of L-alanine to a crystallisation apparatus containing an aqueous suspension of L-alanine; b2) continuously removing water from the aqueous suspension of L-alanine contained in the crystallisation apparatus to maintain conditions of controlled supersaturation; b3) continuously removing the aqueous suspension of L-alanine from the crystallisation apparatus.

7. The method of claim 6, where a portion of the aqueous suspension of L-alanine removed in step b3) is mixed with the aqueous solution of L-alanine of step b1) and the mixture is fed back it into the crystallization apparatus.

8. The method of claim 7, where the mass ratio of the mixture which is fed back it into the crystallization apparatus and the aqueous solution of L-alanine, mixed with the suspension, is at least 4:1.

9. The method of claim 1, where the solid content of the aqueous suspension is from 5 to 30% by weight, based on the weight of the suspension.

10. The method of claim 1, where the crystallization is effected in a crystallizer, selected from a forced circulation crystallizer, draft tube crystallizer, a draft tube baffled crystallizer, an Oslo-type crystallizer and an induced forced circulation crystallizer.

11. The method of claim 1, where the crystallization of L-alanine comprises at least two subsequent crystallization steps.

12. The method of claim 11, where the crystalline L-alanine obtained in a precedent crystallization step is dissolved in a mixture of a mother liquor of the subsequent crystallization step with water to obtain an aqueous solution of L-alanine, from which L-alanine is crystallized in the subsequent crystallization step.

13. The method of claim 1, where the aqueous solution of L-alanine provided in step a) does not contain more than 100 ppm of solid insoluble material.

14. The method of claim 1, where the aqueous solution of L-alanine provided in step a) has been filtered to remove solid insoluble material.

15. The method of claim 1, where the aqueous solution of L-alanine provided in step a) contains at least one amino acid selected from the group consisting of D-alanine, L-valine, L-leucine, L-lysine, L-asparagine, L-glutamine, and L-arginine.

16. The method of claim 1, where the aqueous solution of L-alanine provided in step a) is obtained by a fermentation process.

17. The method of claim 9, where a solid content of the aqueous suspension is from 20 to 25%, by weight, based on the weight of the suspension.

Description

DESCRIPTION OF THE FIGURES

[0048] The process according to the invention is described in detail hereinafter with reference to FIGS. 1 to 7. The figures shown serve for illustration and are not intended to restrict the invention thereto.

[0049] FIG. 1 shows a basic flow chart of the process according to the invention.

[0050] FIG. 2 shows one embodiment of a forced circulation crystallizer.

[0051] FIG. 3 shows another embodiment of a forced circulation crystallizer, in this case a draft baffle crystallizer.

[0052] FIG. 4 shows an embodiment of induced forced circulation crystallizer.

[0053] FIG. 5 shows a block diagram of an embodiment of a multi-stage process according to the invention.

[0054] FIG. 6 shows a block diagram of a preferred embodiment of a multi-stage process according to the invention.

[0055] FIG. 7 shows schematically one crystallization stage according to the invention.

[0056] FIG. 8 Microphotography of crystals obtained from comparative experiment 1.

[0057] FIG. 9 Microphotography of crystals obtained from comparative experiment 2.

[0058] FIG. 10 Microphotography of crystals obtained from example 1 according to the invention.

[0059] In the figures, the following reference symbols are used:

[0060] C crystalline phase/crystals

[0061] CR crystallization

[0062] D discharge

[0063] F feed

[0064] L liquor

[0065] ML mother liquor

[0066] MLR recycled mother liquor

[0067] P product

[0068] R recycled suspension

[0069] RL residual liquor

[0070] S fresh solution

[0071] SLS solid/liquid separation

[0072] V vapor

[0073] W condensed vapor (liquid water)

[0074] WL wash liquid

[0075] i index for the stage

[0076] 1 crystallizer

[0077] 2 heat exchanger

[0078] 3 separator

[0079] 4 circulation pump

[0080] 5 concentrate pump

[0081] 6 compressor for vapor

[0082] 10 inlet

[0083] 11 slurry withdrawal

[0084] 12 suspension outlet

[0085] 13 liquid withdrawal/overflow

[0086] 14 draft tube

[0087] 15 demister

[0088] 16 vapor outlet

[0089] 17 settling zone

[0090] 18 agitator

[0091] 19 inducer

[0092] 20 vapor separation zone

[0093] 21 active volume

[0094] As illustrated in FIG. 1, a fresh stream S containing an aqueous solution of L-alanine is combined with a recycle stream R and heated in a heat exchanger 2 to a temperature of at least 50° C., for example in the range of from 60° C. to 105° C., to give an aqueous solution of L-alanine as feed stream F. The heat exchanger 2 can be arranged either horizontally or vertically depending on the specific requirements. The feed F is then fed to a continuously operated crystallizer 1. The crystallizer 1 contains as active volume an aqueous over-saturated suspension of L-alanine with a solids content of 5% to 30% by weight, for example from 20% to 25% by weight, based on the weight of the suspension. Feeding the under-saturated aqueous solution of L-alanine F into the active volume and removing water at the same time, the concentration of L-alanine in the over-saturated suspension, i.e. in the active volume of the crystallizer 1 is levelled off. The controlled supersaturation of L-alanine in the aqueous suspension is effected at a temperature of at least 50° C., for example in the range of from 60° C. to 105° C., and at reduced pressure, for example in the range of from 120 mbar to 800 mbar.

[0095] Water is removed from the aqueous suspension of L-alanine by evaporation, the water vapor V being withdrawn at the head from the crystallizer 1. The vapor V can be further conveyed via a compressor 6 to heat the heat exchanger 2, conducted for example in countercurrent to the feed F to be heated, and leaving the heat exchanger 2 as condensate W.

[0096] A discharge D of the slurry containing crystalline L-alanine is removed at the lower end from the crystallizer 1. From the discharge D, a part stream is taken as recycle stream R and conveyed via a recycling pump 4 to be mixed with the fresh stream S before, on or after entry into the heat exchanger 2. The discharge D will be portioned in such a way that the mass ratio of the recycle stream R to the fresh stream S is preferably greater than 5, in particular greater than 10, greater than 20, for example in the range of from 40:1 to 60:1.

[0097] The other part of the discharge D is routed by means of a concentrate pump 5 to a separator 3. In the separator 3, the slurry D is separated to obtain mother liquor ML and crystalline L-alanine as product P. If desired, the mother liquor ML can be recycled to the inventive process or a preceding stage.

[0098] Alternatively, a discharge D of the slurry containing crystalline L-Alanine is removed on the side of the lower end from the crystallizer 1. The discharge D is routed by means of a concentrate pump 5 to a separator 3. In the separator 3, the slurry D is separated to obtain mother liquor ML and crystalline L-alanine as product P. If desired, the mother liquor ML can be recycled to the inventive process or a preceding stage. A second discharge is removed as recycle stream R in the center part of the lower end from the crystallizer 1. The recycle stream R is conveyed via a recycling pump 4 to be mixed with the fresh stream S before, on or after entry into the heat exchanger 2. The mass ratio of the recycle stream R to the fresh stream S is greater than 5, in particular greater than 10, greater than 20, for example in the range of from 40:1 to 60:1. This alternative withdrawal of two different slurries can prove in particular advantageous if the slurry D taken at the side of the crystallizer is thicker or contains crystals of a different size distribution than the slurry R taken at the bottom of the crystallizer 1.

[0099] The crystallization may be preferably effected in a continuously operated crystallizer, for example a forced circulation crystallizer, a draft tube crystallizer or a draft tube baffled crystallizer, or in particular in an induced forced circulation crystallizer.

[0100] FIG. 2 shows a draft tube crystallizer. Superheated aqueous solution of L-alanine F is fed to the crystallizer 1 via an inlet 10, flows upward through a draft tube 14 and returns downward along the outer side of the draft tube 14.

[0101] Water evaporated from the suspension in the active volume 21 rises as vapor V to the head of the crystallizer 1. The vapor V passes a vapor separation zone 20 and a demister 15 to remove liquid droplets and leaves the crystallizer 1 via a vapor outlet 16. The vapor V is further conveyed via a compressor 6 to heat the heat exchanger 2, conducted for example in countercurrent to the feed F to be heated, and leaving the heat exchanger 2 as condensate W.

[0102] Around the active volume 21, a settling zone 17 may be arranged. Via a suspension outlet 12 in the lower region of the active volume 21, suspension R is removed and combined with the fresh solution S. The combined stream of R and S is recycled via a circulation pump 4 through a heat exchanger 2 as feed F into the crystallizer. The circulation pump 4 provides for the necessary agitation of the suspension mixed with the incoming solution F and effects the circulation of the suspension within the active volume 21.

[0103] Via a slurry withdrawal 11 situated at the bottom of the crystallizer 1 below the active volume 21, slurry D is removed from the crystallizer 1. The withdrawn slurry D contains the desired crystalline L-alanine.

[0104] FIG. 3 shows a draft tube baffled crystallizer with forced circulation. Superheated aqueous solution of L-alanine F is fed to the crystallizer 1 via an inlet 10, flows upward through a draft tube 14 and returns downward along the outer side of the draft tube 14. A bottom entry agitator 18 provides for the necessary agitation of the suspension mixed with the incoming solution F at moderate energy consumption and effects the circulation of the suspension within the active volume 21.

[0105] Water evaporated from the suspension in the active volume 21 rises as vapor V to the head of the crystallizer 1. The vapor V passes a vapor separation zone 20 and a demister 15 to remove liquid droplets and leaves the crystallizer 1 via a vapor outlet 16.

[0106] Peripheral to the active volume 21, a settling zone 17 is arranged by means of baffles. In the settling zone 17, excess mother liquor L and/or fines can be withdrawn for further processing at an overflow 13 in the upper region of the settling zone 17. This basically clear liquor L can be recycled to the process to regulate the temperature and/or the concentration of the solution of L-alanine at any stage.

[0107] Via a suspension outlet 12 in the lower region of the settling zone 12, suspension R is removed and recycled to be mixed with the fresh feed stream S.

[0108] Via a slurry withdrawal 11 situated below the settling zone 12, slurry D is removed from the crystallizer 1. The withdrawn slurry D contains the desired crystalline L-alanine as product P.

[0109] The induced forced circulation crystallizer shown in FIG. 4 operates similarly to the forced circulation crystallizers shown in FIGS. 2 and 3 as explained above. Different to the embodiment shown in FIG. 3, the induced forced circulation crystallizer works without any internal agitation device.

[0110] Superheated aqueous solution of L-alanine F is fed to the crystallizer 1 via an inlet 10, flows upward through a draft tube 14 and returns downward along the outer side of the draft tube 14. Water evaporated from the suspension in the active volume 21 rises as vapor V to the head of the crystallizer 1. The vapor V passes a vapor separation zone 20 and a demister 15 to remove liquid droplets and leaves the crystallizer 1 via a vapor outlet 16.

[0111] Peripherical to the active volume 21, a settling zone 17 is arranged. Liquor L is withdrawn at a liquid withdrawal 13 in the upper region of the settling zone 17. This basically clear liquor L is recycled via the circulation pump 4. Via a suspension outlet 12 below the settling zone 12, suspension R is removed and combined with the clear liquor L in an external circuit. Fresh solution S is fed to the recycled stream L before, simultaneously or after combination with stream R. The combined recycled stream is heated in a heat exchanger (not shown in the figure) and fed to the crystallizer 1 as feed F. Analogously to the embodiment shown in FIG. 2, the vapor V may be used to heat the heat exchanger 2.

[0112] The throughput of the circulation pump 4 provides for the syphoning of the recycled suspension R and the necessary agitation of the suspension within the active volume 21. No further agitation devices are required, so that the crystals in the suspension are treated with the least possible strain.

[0113] Via a slurry withdrawal 11 situated at the bottom of the crystallizer 1 below the active volume 21 and below the settling zone 12, slurry D is removed from the crystallizer 1. The withdrawn slurry D contains the desired crystalline L-alanine as product P.

[0114] In the multi-stage process according to FIG. 5, the crystallization is performed in n stages. A feed F is introduced into a first crystallization stage (i=1). Solvent is removed by from the first crystallization e.g. by way of evaporation. The suspension is separated into residual liquor RL and a first crystalline phase C.sub.1. The first crystalline phase C.sub.1 is passed into a second crystallization stage (i=2). Mother liquor from the second crystallization stage (i=2) is recycled into the first crystallization stage (i=1), e.g. by mixing it with water and using the mixture for dissolving the crystalline phase C.sub.1 obtained in the first crystallization stage. In each crystallization stage (i=2 to n), water is removed, e.g. by withdrawn it in the form of solvent vapor V and the suspension is separated into mother liquor ML and a crystalline phase C. The crystalline phase from each crystallization stage (i) is passed into the following crystallization stage (i+1). Mother liquor from each crystallization stage (i) is recycled into the previous crystallization stage (i−1), for example by mixing it with water and utilizing the mixture for dissolving the crystalline L-alanine from the previous crystallization stage. A crystalline phase containing the desired L-alanine crystals is withdrawn from the last stage n. The number of stages n depends on the desired quality of the crystals in respect of form, purity, flow characteristics and storage properties.

[0115] In the multi-stage process according to FIG. 6, the crystallization is performed in n stages the first stage (i=1) being a stripping section. The flow is similar to the flow described in FIG. 4, but feed F is introduced between the stripping stage (i=1) and the second crystallization stage (i=2). In general, the process according to FIG. 6 gives higher yields of the desired product.

[0116] A crystallization stage (i) according to FIG. 7 comprises an apparatus each for crystallization CR.sub.i and for solid/liquid separation SLS.sub.i. Apparatuses employed for the crystallization CR.sub.i are in general crystallizers suitable for crystalline suspensions such as stirred tank reactors, e.g. Swenson type crystallizers, forced circulation crystallizers, e.g. Oslo type reactors, draft tube reactors, draft tube baffled crystallizer (see FIG. 3), or induced forced circulation crystallizer (see FIG. 4). Apparatuses employed for the solid/liquid separation SLS.sub.i are in general centrifuges, decanters, filters, filter presses, or washing towers.

[0117] The feed F.sub.i for each stage (i) comprises suspension containing the crystalline phase C.sub.i−1 from the previous stage (i−1) and/or fresh feed F, respectively, as well as recycled mother liquor MLR.sub.i. Distillate is withdrawn from the crystallization CR.sub.i in the form of solvent vapor V.sub.i. Subsequently, the suspension is separated in the solid/liquid separation SLS.sub.i into mother liquor ML.sub.i and a crystalline phase C.sub.i. The crystalline phase C.sub.i from each crystallization stage (i) can be passed as feed F.sub.i+1 into the following crystallization stage (i+1) or be withdrawn as product, respectively. One portion of mother liquor ML.sub.i from each crystallization stage (i) is recycled into the same stage as MLR.sub.i. The rest of mother liquor ML.sub.i from each crystallization stage (i) can be recycled into the previous crystallization stage (i−1) or be withdrawn, respectively.

[0118] To enhance the purity of the product L-alanine, washing liquid WL.sub.i can additionally be employed in the solid/liquid separation SLS.sub.i. As washing liquid WL.sub.i cold water or cold mother liquor of a subsequent crystallization stage (i+1) is preferably used.

[0119] Comparative Experiment 1:

[0120] The experiment was conducted in a 1 liter double jacketed vessel, equipped with a pitch blade stirrer and 3 baffles. A 19.5 wt % solution of pure L-alanine in deionized water was added to the vessel and seeded with 0.5 wt %, based on the mass of the alanine solution, of crystalline L-alanine. The vessel was heated to 60° C. with stirring at 600 min.sup.−1 and the pressure was slowly reduced to 170 mbar thereby removing water by evaporation until the amount of evaporated water was 45 wt % of the initial alanine solution. Thereby, solid L-alanine was obtained as compact rod-shaped crystals as can be seen from FIG. 8.

[0121] Comparative Experiment 2:

[0122] The experiment was conducted as described for comparative experiment 1, with the except that the initial alanine solution contained 0.1 wt % of L-valine. Thereby, solid L-alanine was obtained as needle-shaped crystals as can be seen from FIG. 9.

EXAMPLE 1

According to the Invention

[0123] The experiment was conducted in a 1 liter double jacketed vessel as described for comparative experiment 1. The vessel was connected with a feed-line and a product buffer for removal of the suspension. The vessel was operated continuously as a MSMPR-crystallizer (mixed suspension mixed product removal). A solution of L-alanine obtained from a fermentation having a concentration of 17.8 wt % of L-alanine, 0.085 wt % of L-valine and 0.35% of organic impurities different from L-valine was continuously fed to the vessel with a feed rate of 1040 g/h. The vessel contained a 20 wt % aqueous suspension of crystalline L-alanine and it was operated at 60° C. and 180 mbar with a stirring speed of 600 min.sup.−1. The circulation volume flow in the vessel was 0.00273 m.sup.3/s. Water was continuously removed by evaporation such that the degree of evaporation, i.e. the relative flow of evaporated water based on the feed flow, was 50%. Under these conditions, the degree of supersaturation, i.e. the ratio c/c* was about 1.00005. By this process, the solid crystalline L-alanine was obtained as compact rods as can be seen from FIG. 10.