METHOD FOR THE PRODUCTION OF A DICARBOXYLIC ACID

Abstract

The present invention is related to a method for the production of a dicarboxylic acid, wherein the method comprises a bioconversion step, wherein in the bioconversion step, the dicarboxylic acid is produced from a precursor compound contained in a medium; and a purification step for purifying the dicarboxylic acid from the medium, wherein the purification step comprises (a) a nano-diafiltration step and/or (b) a distillation step or an evaporation step or both a distillation step and an evaporation step, wherein preferably if the purification step comprises (a) the nano-diafiltration step and (b) the distillation step or the evaporation step or both the distillation step and the evaporation step, the nano-diafiltration step is carried out prior to the distillation step and the evaporation step, respectively, and
wherein the dicarboxylic acid is selected from the group comprising decanedioic acid, dodecanedioic acid, tetradecanedioic acid and hexadecanedioic acid, preferably the dicarboxylic acid is dodecanedioic acid (DDDA).

Claims

1. A method for the production of a dicarboxylic acid, wherein the method comprises optionally, a bioconversion step, wherein in the bioconversion step, the dicarboxylic acid is produced from a precursor compound contained in a medium; and a purification step for purifying the dicarboxylic acid from the medium, wherein the purification step comprises (a) a nano-diafiltration step and/or (b) a distillation step or an evaporation step or both a distillation step and an evaporation step, wherein preferably if the purification step comprises (a) the nano-diafiltration step and (b) the distillation step or the evaporation step or both the distillation step and the evaporation step, the nano-diafiltration step is carried out prior to the distillation step and the evaporation step, respectively, and wherein the dicarboxylic acid is selected from the group comprising decanedioic acid, dodecanedioic acid, tetradecanedioic acid and hexadecanedioic acid, preferably the dicarboxylic acid is dodecanedioic acid (DDDA).

2. The method of claim 1, wherein if the purification step comprises the nano-diafiltration step, the medium containing the dicarboxylic acid is subjected to the nano-diafiltration step, wherein the retentate of the nano-diafiltration contains the dicarboxylic acid.

3. The method of claim 1, wherein the membrane used in the nano-diafiltration step has a cut-off value of between 150 Da and 300 Da, preferably the cut-off value is ≤150 Da.

4. The method of claim 1, wherein the distillation step is a thin film distillation step.

5. The method of claim 1, wherein the evaporation step is a thin film evaporation step.

6. The method of claim 1, wherein the evaporation step is a short path evaporation step.

7. The method of claim 1, wherein the dicarboxylic acid containing retentate of the nano-diafiltration step is subjected to an acidification step, preferably in the acidification step, sulfuric acid is added to the dicarboxylic acid containing retentate of the nano-diafiltration step and the dicarboxylic acid is precipitated from the retentate, and the precipitated dicarboxylic acid is optionally washed.

8. The method of claim 1, wherein the method does not comprise the nano-diafiltration step, and wherein the dicarboxylic acid obtained from the bioconversion step is subjected to the distillation step.

9. The method of claim 8, wherein the dicarboxylic acid obtained from the bioconversion step or from a stage of the purification step carried out prior to the distillation step is obtained as precipitated dicarboxylic acid, preferably the dicarboxylic acid is obtained as precipitated dicarboxylic acid from an acidification step.

10. The method of claim 7, wherein the precipitated dicarboxylic acid is subjected to a melting step, wherein in the melting step, the precipitated dicarboxylic acid is melted, preferably at a temperature of about 140° C. and subjected to the distillation step.

11. The method of claim 10, wherein in the distillation step and/or in the evaporation step, the melted dicarboxylic acid is heated so as to obtain vaporized dicarboxylic acid, preferably the melted dicarboxylic acid is heated in a distillation column so as to obtain vaporized dicarboxylic acid.

12. The method of claim 11 wherein the conditions for vaporization of the dicarboxylic acid ranges from 190° C. at 1 hPa to about 240° C. at 10 hPa.

13. The method of claim 11, wherein the dicarboxylic acid is vaporized in a thin-film evaporator, wherein, preferably in the thin-film evaporator a heavy-boiler is separated from the dicarboxylic acid, more preferably the dicarboxylic acid obtained from the thin-film evaporator is conducted to a rectification column, wherein, preferably, in the rectification column the dicarboxylic acid is separated from the low-boiler, more preferably the dicarboxylic acid is introduced to a feed tray at the middle section of the rectification column.

14. The method of claim 1, wherein the method does not comprise the distillation step, the evaporation step or a combination of the distillation step and the evaporation step, and wherein the precipitated dicarboxylic acid is dissolved in a fluid, preferably the fluid is water, an organic solvent or a mixture of water and an organic solvent.

15. The method of claim 14, wherein the fluid containing the dicarboxylic acid is subjected to a crystallization step, wherein the dicarboxylic acid is crystallized from the dicarboxylic acid containing fluid in the crystallization step, whereupon crystallized dicarboxylic acid and a supernatant are provided, preferably the crystallized dicarboxylic acid is removed from the supernatant, preferably by centrifugation or filtration.

16. The method of claim 15, wherein the crystallized dicarboxylic acid removed from the supernatant is subject to a washing step and/or drying step.

17. The method of claim 1, wherein (a) the precursor compound comprises or is an ethyl ester or methyl ester of the monocarboxylic acid of the dicarboxylic acid to be produced, preferably the precursor is or comprises an ethyl ester or methyl ester, preferably an ethyl ester, of decanoic acid in case the dicarboxylic acid to be produced is decanedioic acid; an ethyl ester or methyl ester, preferably an ethyl ester, of dodecanoic acid in case the dicarboxylic acid to be produced is dodecanedioic acid; an ethyl ester or methyl ester, preferably an ethyl ester, of tetradecanoic acid in case the dicarboxylic acid to be produced is tetradecanedioic acid; and an ethyl ester or methyl ester, preferably an ethyl ester, of hexadecanoic acid in case the dicarboxylic acid to be produced is hexadecanedioic acid; and/or (b) the precursor compound comprises or is an alkane compound, wherein preferably the alkane compound is selected from the group comprising decane, dodecane, tetradecane and hexadecane, more preferably the precursor compound is or comprises decane in case the dicarboxylic acid to be produced is decanedioic acid; dodecane in case the dicarboxylic acid to be produced is dodecanedioic acid; tetradecane in case the dicarboxylic acid to be produced is tetradecanedioic acid; and hexadecane in case the dicarboxylic acid to be produced is tetradecanedioic acid.

18. The method of claim 1, wherein in the bioconversion step bioconversion of the precursor compound is effected by a biocatalyst, preferably the biocatalyst is a microorganism and more preferably the biocatalyst is a yeast.

Description

[0257] The present invention is now further illustrated by the following Figs. from which further features, embodiments and advantages of the present invention may be taken. More specifically,

[0258] FIG. 1 shows a block flow diagram for an acidification and a precipitation step;

[0259] FIG. 2 shows a flow diagram for the treatment of raw DDDA in a thin film evaporator and subsequent treatment in a rectification column;

[0260] FIG. 3 shows a block flow diagram of the fermentation step; and

[0261] FIG. 4 shows a block flow diagram of an embodiment of the method for producing DDDA according to the first and second aspect.

[0262] FIG. 1 shows a block flow diagram for an acidification and a precipitation step. In an embodiment of the method of the first aspect and the second aspect of the invention, nano-diafiltration retentate is added to an agitated vessel and mixed with activated carbon and filter aid. The solution is heated to about 60° C. and mixed for 10 min. The mixture is then filtered through a 30μm polypropylene filter to remove the activated carbon. This activated carbon filtration step uses an activated carbon to DDDA mass ratio of about 1:10, whereby other ratios may be used and determined, respectively, by routine tests.

[0263] The filtered solution is then heated to 96-100° C. Sulfuric acid (98% (wt/wt)) is added and mixed with the nano-diafiltration retentate to achieve a pH of 1.6-1.8 at 100° C. The sulfuric acid is charged at a continuous rate over a two-hour period. The final amount of concentrated sulfuric acid fed is about 4% volume sulfuric acid/volume of charged filtrate obtained from the ultrafiltration step. During acid addition the product precipitates out of solution. Once acid addition is complete, the solution is held at a temperature of about 90° C. for 30 minutes. Then the solution is cooled to 25-30° C. The precipitated DDDA is separated via an isolation device and washed with de-ionized water. The purpose of this step is to remove ions, such as those from media components, base additions, and sulfate from the acidification step. The preferred technology is a pusher centrifuge, belt filter or rotary vacuum filter capable of washing while isolating a dewatered cake.

[0264] FIG. 2 shows a diagram for the treatment of raw DDDA in a thin film evaporator and subsequent treatment in a rectification column.

[0265] Liquid DDDA at a temperature of 140° C. is directed to a thin film evaporator and vaporized there. Evaporation temperature is preferably about 190° C. at 1 mbar so as to provide optimum separation. The high boilers (referred to as “heavies” in FIG. 2) do not change to the gas phases at this temperature and are removed from the thin-film evaporator, for example by wipers. The conditions for evaporation range from 190° C. at 1 mbar to about 240° C. at 10 mbar.

[0266] FIG. 3 shows a block flow diagram of the fermentation and bioconversion part of an embodiment of the method for the production process of a dicarboxylic acids of the present invention. In a first step, the precursor compound for the dicarboxylic acid production is produced, in the case of dodecanedioc acid (DDDA) this is ethyl laurate. Ethyl laurate is produced in an esterification reaction from lauric acid and ethanol in the presence of sulfuric acid and subsequently distilled to high purity. This step is called “Ethyl Laurate Prep” in FIG. 3 and depicted in the upper line of FIG. 3; this step may be carried out either internally or by a supplier of ethyl laurate.

[0267] In the lower part of FIG. 3, the preparation of fermentation medium is depicted, whereby the components listed are mixed into water and passed through a sterile filter before they enter the seed train or the main fermentor. In the middle part, dextrose solution is prepared and such dextrose solution, also after passage through sterile filtration or heat sterilization, enters the seed train or main production fermentor. The seed train consists of several consecutive fermenters of different sizes and is used to cultivate the microorganism capable of producing the dicarboxylic acid carrying out, and respectively, of carrying out the bioconversion step. After the seed culture has been transferred to the production fermentor the microorganism used as a biocatalyst is cultivated to a cell density sufficient to carry out bioconversion, typically 3 to 4 days of cultivation time. Then the precursor is continuously added to the production fermenter under continuous aeration and addition of medium and stirring. The biocatalyst is converting the precursor compound to the dicarboxylic acid, in case of ethyl laurate dodecanedioic acid is formed. After a period of 1 to 2 days all precursor is converted to product and small amounts of byproduct. The bioconversion broth is then directed to the downstream and purification processes further disclosed herein.

[0268] Vaporized DDDA is directed at the same temperature and pressure to a rectification column, preferably directed to half the height of the rectification column, and separated by means of the trays from low-boilers such as fatty acids, lactams lactones and/or short dicarboxylic acids. In an embodiment, the rectification comprises at least eight theoretical trays. Distilled liquid DDDA is collected at the bottom of the rectification column.

[0269] FIG. 4 shows a block diagram of an embodiment of the method for the production of DDDA according to the first and the second aspect.

[0270] In a fermentation vessel, a microorganism such as yeast Candida vishvanathii is grown to reach the biomass necessary to for the bioconversion step. In the bioconversion step, paraffin or fatty acids used as a precursor compound is converted to the dicarboxylic acid, which is subsequently treated in the same vessel with ammonia after finishing bioconversion. The dicarboxylic acid is then transformed into the ammonia salt of the acid and therefore soluble in the fermentation broth. The biomass is subsequently separated by means of a centrifuge and fermentation broth is fed to an ultrafiltration unit to remove final remains of biomass and cell debris. The now clarified broth is nano filtrated where the di-ammonium salt of the dicarboxylic acid is collected on the retentate side of the nano filtration. As the nano filtration is working as dia-filtration the major part of the impurities with low molecular weight is washed out and leaves the ammonium salt of the dicarboxylic acid more purified. As an alternative, the nano filtration can be bypassed, but in such case the broth contains more impurities in comparison to the nano filtrated material. In the next step, the dicarboxylic acid is precipitated by addition of sulfuric acid, as the solubility of the dicarboxylic acid is very low. The precipitate is then filtered or alternatively centrifuged from the ammonium sulphate solution, washed with cold water and fed to a fluidized bed dryer unit. The ammonium sulphate solution is concentrated to 40% dry material and either crystallized or granulated. The dried dicarboxylic acid can be purified by two different methods. One way is to melt the dicarboxylic acid in a melting vessel and feed the dicarboxylic acid to a thin-film evaporation unit. In the thin-film evaporation unit, the dicarboxylic acid is evaporated on the wiped heating wall of the evaporation column and the vapour is brought to mid tray of a rectification column. The distilled dicarboxylic acid is then taken from the bottom of the rectification column. The alternative way to purify the dicarboxylic acid is to resolve the dicarboxylic acid in water or an organic solution such as acetic acid. The dicarboxylic acid solution is treated with heat and activated carbon to remove impurities and colour bodies. After removal of the activated carbon the solution is cooled down and the purified dicarboxylic acid precipitates. The crystalline dicarboxylic acid will be washed with cold water and dried.

EXAMPLE: Purification of Fermentation Broth Containing DDDA

[0271] Dodecanedioic acid was produced by fermentation using Ethyl Laurate as a starting material on 18 L scale. After fermentation, the broth contained next to approx. 144 g/L (11.3 mol) product or DDDA and reaction intermediates also biomass, salts, minerals and nutrients like glucose, amino acids and proteins. The pH of the liquid was 6.6 and the temperature 23° C. The suspension was kept stirring while aqueous ammonium hydroxide solution (25%) was slowly added to the broth to solubilize the DDDA by forming the corresponding diammonium salt. In total 4.2 L (26.9 mol) ammonium hydroxide solution was added under stirring to the fermentation broth over a duration of 2 h, while the temperature was maintained under 30° C. and until the resulting pH was at 10.3. After addition of alkali the suspension was centrifuged to remove biomass and undissolved solids.

[0272] The 21.5 L aqueous solution after centrifugation, were subjected to an ultrafiltration to remove remaining fine suspended solids and large molecules from the solution. The ultrafiltration employs a spiral-wound membrane or alternatively a Hollow Fiber Membrane with a MWCO of 10,000 to 20,000 Da. There are numerous membranes available on the market, fabricated by Dow, GE, Hydranautics, Koch, Millipore and other suppliers. The membrane used for this trial was a GE Healthcare PES hollow fiber membrane with a MWCO of 10,000 Da. The membrane area was 4.4 m.sup.2. At the beginning the temperature of the aqueous solution containing the Ammonia salt of the DDDA was measured with 18.5° C. The initial pressure was set at 1.3 bar at the beginning of the filtration. Surprisingly, there was no permeate detected even after increasing the pressure to 2 bar. After 30 min the temperature was raised to 30° C., the pressure adjusted to 1.3 bar and the flux through the membrane immediately started at 19.8 L/m.sup.2*h. At the end of the Ultrafiltration 16 L Permeate was collected, the rest was left as retentate and in the dead volume of the Ultrafiltration unit. Such strong context between concentration of DDDA, temperature and the filterability was not expected or seen with other organic di-acids before.

[0273] The permeate was collected and 5 L were separated for precipitation of DDDA. Sulfuric Acid (95% solution) had been added slowly under strong heat development and vigorous stirring to the solution. The temperature was kept below 50° C. and the addition was stopped at a pH of 3 with all DDDA precipitated. The precipitated DDDA was forming a highly viscous suspension. The DDDA was filtered in a vacuum suction filter with a pore size of 0.2 μm. To our surprise the filtration was fast and the filter cake could be filtered easily. The cake was taken out from the filter and re-suspended in 2 L demineralized water at 18° C. The formed slurry was again filtered in a vacuum suction filter with same pore size. Even though the filter cake looked and felt rather dry, it did contain more than 40% moisture. Therefore, remaining filter cake was taken and stored for 24 h in a drying cabinet at 80° C. under reduced pressure and stored for later analysis and short path evaporation.

[0274] The remaining 11 L from the previous step were further purified by nano-dia-filtration. Nanofiltration membranes provide a high rejection of multivalent Ions and larger molecules, while selecting of monovalent ions and small uncharged molecules as for example monosaccharides. Nanofiltration Membranes will be manufactured at GE, DuPont, Synder and other specialized companies. The membranes will be produced as spiral wound or hollow fiber membranes with a MWCO between 150 and 800 Da. In our case we used a Synder 1810, NFS-TFC spiral wound element with a MWCO of 100 to 250 Da. The membrane area was small with 0.4 m.sup.2. The solution was still at a temperature of 30° C. and the initial pressure was set at 28 bar. Again, we could not detect any permeate which could not be expected as earlier results with lower concentration of DDDA did show high Flux even at lower temperatures. The temperature was raised to 48° C. and the pressure increased to 29.5 bar as this is the max. Design Pressure and Temperature of the Membranes in use. A small Flux rate to the permeate side started with 2 to 3 L/m.sup.2*h. After 1 h of filtration only 2 L could be found in the permeate, therefore 9 L demineralized water was added as diafiltration water. The filtration commenced until the volume of the retentate reached approx. 9 L. The permeate was separated for later analysis. The context between the concentration of DDDA, the temperature and the filterability is crucial for setting the parameters of such NF operation. A concentration of DDDA between 60 to 100 g/l combined with a temperature above 40° C. is necessary to achieve the desired depletion of monovalent Ions and monosaccharides coming from fermentation.

[0275] The Analysis of the Retentate after nano-diafiltration showed a depletion of monosaccharide (Glucose) by 70%.

[0276] The Retentate was collected for precipitation of DDDA. Sulfuric Acid (95% solution) has been added slowly under strong heat development and vigorous stirring to the solution. The temperature was kept below 50° C. and the addition was stopped at a pH of 3 with all DDDA precipitated. The precipitated DDDA was forming a highly viscous suspension. The DDDA was filtered in a vacuum suction filter with a pore size of 0.2 μm. To our surprise, the filtration was fast and the filter cake could be filtered easily. The cake was taken out from the filter and re-suspended in 5 L demineralized water at 18° C. The formed slurry was again filtered in a vacuum suction filter with same pore size and de-watered. The remaining filter cake was taken and stored for 24 h in a drying cabinet at 80° C. under reduced pressure.

[0277] The dried DDDA from the precipitation after Ultrafiltration and the dried DDDA from precipitation after Nanofiltration were slowly heated and molten in the drying cabinet at 150° C. There could be seen a difference in the colour, as the molten DDDA after Ultrafiltration was containing more colour bodies than the DDDA after Nanofiltration.

[0278] The Short Path Evaporation normally operates within a pressure range of 0.001 to 1 mbar.

[0279] The molten DDDA flows along the inside wall of the evaporator as a liquid film from the supply point to the discharge point. The residence time in the apparatus is very short with minimal thermal stress to avoid any condensation reaction of the DDDA, e.g. forming anhydrates. The wiper system for the operation inside the evaporator ensures an even distribution of molten DDDA on the evaporator surface and ideal mixing which flows downwards. This means that DDDA is continuously brought to the film surface and evaporates more efficiently. Heating of the evaporator is made via heat transfer medium, e.g. thermal oil or steam.

[0280] The Short Path Evaporator has an internally positioned condenser. The ‘short path’ of the vapor phase to the condenser results in only little pressure loss, meaning that extremely low pressures can be achieved. Therefore, in the Short Path Evaporator, distillation can take place at lower temperatures, for DDDA it ranges between 190 to 240° C., depending to the vacuum applied.

[0281] The system used was a Short Path Evaporator manufactured from VTA and made of Glass with an evaporation surface of 0.06 m.sup.2. We applied a vacuum of 0.002 mbar, the evaporation surface was heated to 210° C., and the condenser had a temperature of 150° C. Under these conditions both samples of DDDA were evaporated.

[0282] The sample after Ultrafiltration was already in the molten state strong coloured. The evaporated and condensed DDDA was slightly coloured when the ratio of evaporated DDDA and remaining liquid substances was kept at 92% evaporate and 8% non-evaporated material. While reducing amount of evaporated DDDA to less than 80%, the colour of the condensed DDDA disappeared. Reducing the amount of evaporated DDDA decreases the yield as more than 20% is not evaporated and seen as loss.

[0283] The sample after Nanofiltration was coloured as well in the molten state but less than the Material after Ultrafiltration. The evaporated and condensed DDDA was not coloured when the ratio of evaporated DDDA and remaining liquid substances was kept at 92% evaporate and 8% non-evaporated material.

[0284] The Analysis of the nano-diafiltrated and distilled material gave following results:

TABLE-US-00002 Dodecanedioic Acid (%): >99.8 (Gas Chromatography) Water (%): not detectable (Karl-Fischer) Ash (ppm): not detectable (Thermo-gravimetric Analysis) Fe (ppm): not detectable (ICP-AES, ICP-MS and AAS) Acetic Acid (ppm): not detectable (Gas Chromatography) Nitrogen (ppm): >20 (Kjeldahl) Sulphur (ppm): not detectable (ICP-AES, ICP-MS and AAS)
The features of the present invention disclosed in the specification, the claims and/or the examples may both separately and in any combination thereof be material for realizing the invention in various forms thereof.