EP1436245A1 - Procede pour separer des sels d'acides organiques contenus dans un bouillon de fermentation et liberer l'acide organique - Google Patents

Procede pour separer des sels d'acides organiques contenus dans un bouillon de fermentation et liberer l'acide organique

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Publication number
EP1436245A1
EP1436245A1 EP02785181A EP02785181A EP1436245A1 EP 1436245 A1 EP1436245 A1 EP 1436245A1 EP 02785181 A EP02785181 A EP 02785181A EP 02785181 A EP02785181 A EP 02785181A EP 1436245 A1 EP1436245 A1 EP 1436245A1
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EP
European Patent Office
Prior art keywords
acid
salt
solution
organic acid
organic
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Application number
EP02785181A
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German (de)
English (en)
Inventor
Matthias Rauls
Hartwig Voss
Tillmann Faust
Thomas Domschke
Martin Merger
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BASF SE
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BASF SE
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Publication of EP1436245A1 publication Critical patent/EP1436245A1/fr
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D307/62—Three oxygen atoms, e.g. ascorbic acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/42—Separation; Purification; Stabilisation; Use of additives

Definitions

  • the present invention relates to a process for isolating salts of organic acids from an aqueous solution, in particular from a fermentation discharge, by partial evaporation crystallization and subsequent or simultaneous displacement precipitation of their salt, and to release the organic acid from the crystals, preferably by means of an electromembrane process.
  • Organic acids are economically important chemicals that are widely used, among other things. find in nutrition, cosmetics or medicine; either as active substances or as intermediates in the manufacture of these substances. Lactic acid is used as a preservative in food and added to pharmaceutical preparations. Lactic acid monomers form the basis for the production of degradable plastics.
  • the polyhydroxyketocarboxylic acid 2-keto-L-gulonic acid (KGS) is a central intermediate in the production of vitamin C.
  • the production of such organic acids and their secondary products is characterized by special requirements in terms of purity and yield in all process stages: for one to enable the end product to be used in human nutrition and the other to reduce manufacturing costs as much as possible.
  • KGS is obtained in a one- or multi-stage fermentative process, for example through the two-stage fermentation of sorbitol via sorbose with suitable, sometimes specially modified microorganisms.
  • KGS is isolated from the fermentation solutions according to different variants using classic procedural basic operations such as ion exchange, crystallization, extraction etc. and converted to ascorbic acid.
  • the product solutions contain a considerable amount of impurities, some of which are strongly colored.
  • impurities some of which are strongly colored.
  • fermentation solutions after only 80% separation of the valuable substance in the resulting mother liquors, there are generally more secondary components than the valuable product. With increasing yield, the co-insulation of impurities is therefore becoming more and more likely.
  • organic acids show a pH- and temperature-dependent tendency to decompose and form disruptive, also colored secondary components under the usual process-technical production and purification conditions.
  • salts of these acids e.g. of sodium 2-keto-L-gulonate (Na-KGS)
  • Na-KGS sodium 2-keto-L-gulonate
  • the salts not only have a lower sensitivity to thermal stress, but can also be isolated at neutral pH values at which the tendency to decompose is lower than in an acidic environment.
  • the purified acid can be obtained from the salts in a further process step, e.g. Release by ion exchange or electrodialysis.
  • EP 0805210 describes the possibilities and limits of isolating Na KGA from a purified fermentation solution by means of evaporation, cooling or displacement crystallization.
  • example 1 it is shown that, in the case of a discontinuous procedure, at least four crystallization stages with subsequent processing of the mother liquors and washing
  • the present invention is therefore based on the problem that when isolating or purifying organic acids from fermentation broths, in particular carboxylic acids, such as e.g. Ketogulonic acids, lactic acid, citric acid, vanillic acid, idonic acid, gulonic acid, especially ascorbic acid, 2, 4-diketo-D-gulonic acid, 2, 5-diketo-D-gulonic acid or 2-keto-L-gulonic acid, thus either strong product impurities in Purchase must be made, which are then separated with a loss in later process stages, or only low yields are achieved with high purities. Due to the high number of process steps, the processes made available in the prior art are e.g. For the preparation of the fermentation broth or to achieve good yields, it is very time-consuming and also ecologically questionable due to the high consumption of energy and organic, largely toxic solvents.
  • carboxylic acids such as e.g. Ketogulonic acids, lactic acid, citric acid, vanillic acid, idonic acid, gulonic
  • the object of the present invention is therefore to provide an advantageous method for isolating free organic acids or their salts economically, ecologically and efficiently from fermentation broths.
  • the present invention relates to a method for isolating an organic acid salt from a fermentation broth, comprising the steps
  • organic acid means a substituted or unsubstituted, branched or unbranched carbon chain of 3 to 20 carbon atoms, preferably 4 to 10 carbon atoms, more preferably 5 to 7 carbon atoms with one or more carboxyl group (s) ( -COOH).
  • An “organic acid” is thus preferably understood to mean a carboxylic acid.
  • the organic acid can, for example, by fermentative conversion of saccharides, for example Starch, sucrose or glucose can be produced.
  • organic acids are, for example, ketogulonic acids, lactic acid, citric acid, vanillic acid, idonic acid, gulonic acid, in particular ascorbic acid, 2, 4-ketogulonic acid, 2, 5-deceto-D-gulonic acid or 5 2-keto-L-gulonic acid (KGS).
  • the term organic acids also includes, for example, acetic acid, maleic acid, malonic acid, salicylic acid, glycolic acid, glutaric acid, benzoic acid, propionic acid, oxalic acid, stearic acid, ascorbic acid, glutamic acid, etc. or mixtures thereof.
  • the organic acid is preferably 2-keto-L-gulonic acid 10 (KGS).
  • partial evaporation crystallization (or equivalent here “partial evaporation crystallization”) is understood to mean that the fermentation broth is used for
  • Part of an evaporative crystallization can be replaced by a "cooling crystallization".
  • the partial evaporative crystallization can also be carried out
  • partial cooling crystallization means that the fermentation broth, in particular the fermentation solution already depleted in organic salt in the evaporation crystallization, is cooled in this way
  • the salts of the acid to be isolated in particular of lactic acid, citric acid, ascorbic acid, gulonic acid or 2-keto-L-gulonic acid, are partially precipitated.
  • Partial precipitation is understood to mean that 10 to 95% of the organic salt remains dissolved in the broth after the precipitation.
  • the term “displacement cases” means that the salts mentioned, in particular of lactic acid, citric acid,
  • ascorbic acid, gulonic acid or 2-keto-L-gulonic acid are precipitated from the aqueous fermentation solution by adding an organic liquid, the organic liquid being miscible with water, the salts mentioned, in particular the salts of lactic acid, citric acid, ascorbic acid, gulonic acid
  • Organic solvents that are miscible with water are polar solvents, for example alkyl alcohols such as methanol, Ethanol, n-butanol, iso-butanol, 1-propanol, 2-propanol, etc. or alkyl ketones such as acetone, 2-butanone, propanone etc.
  • Fermentation broths which is used here synonymously with “fermentation solutions” or “fermentation discharges”, means liquid nutrient media in which organisms, as a rule microorganisms, such as e.g. Protists, e.g. Fungi, yeasts or bacteria, algae or plant or animal cells have been cultivated and which consequently can include these organisms.
  • the term encompasses both media with biomass and media in which the biomass has been reduced or removed, e.g. by filtration, e.g. by cross-flow membrane processes, decanting or centrifuging.
  • Fermentation broths, fermentation solutions or fermentation discharges can contain different amounts of biomass, especially dissolved substances, e.g.
  • Proteins, sugars, peptides, or undissolved components such as e.g. Contain microorganisms or cell components.
  • One or more substances may be dissolved or mixed in the fermentation broth, which preferably improve the extraction, stability or solubility of the ingredients, or preferred properties, e.g. pH, conductivity, salt concentration, etc., such as Salt or buffer solutions.
  • the fermentation broth can also contain a certain portion of an organic, water-miscible solvent, as long as this portion does not lead to precipitation of the salt mentioned.
  • Substances that cause cells to break open can also be present.
  • the term also includes fermentation broths that have been prepared as described herein.
  • the salt of an organic acid is obtained in the literature, from which the acid is then released and crystallized. Especially in the release and crystallization of ketogulonic acid, this leads to a high proportion of by-products, in particular due to undesired ring closures.
  • the processes described in the prior art which are based on isolation of the organic acid or its salts from the fermentation broth by evaporation crystallization, describe yields of only 80 to 90%. Higher yields of 95% can only be achieved by combining several crystallization steps (see above, EP 0805210, EP 0359645).
  • the present invention provides a method which enables the economically and ecologically advantageous isolation of salts of organic acids in yields of more than 90%, preferably more than 95%, in one or two stages.
  • the salt of the organic acid is advantageously first crystallized and only then is the acid released from the redissolved salt.
  • this has the advantage that the high proportion of by-products, e.g. by ring closure.
  • the method according to the invention thus has the advantage over the prior art that it cannot be carried out in just one or two process-economic steps.
  • the process according to the invention since the displacement precipitation takes place from a concentrated fermentation liquor and thus takes place in a smaller volume than in the prior art, the process according to the invention also leads to a substantially lower consumption of organic solvent.
  • the dilution of the originally highly viscous mother liquor with the organic solvent also has the procedural advantage that the solid-liquid separation is facilitated, which in turn leads to higher purity and color depletion.
  • part of the purification process can be carried out under adiabatic conditions, so that there is no need for heating or cooling.
  • the method according to the invention requires little or no preparatory steps for the preparation of the fermentation solution.
  • the method according to the invention makes highly purified substances available at a very early stage, so that in subsequent stages, which are based on the purified substances, the yield and purity of the products are improved.
  • the fermentation solution is only partially, i.e. evaporated to 10 to 95%, preferably to 30 to 90%, more preferably to 50 to 85% or higher depending on the concentration of the starting solution.
  • the maximum degree or range of evaporation of the water contained in the feed depends on the salt concentration in the starting solution.
  • the evaporation range is preferably 95%, more preferably 90%, of the water contained in the feed.
  • the maximum evaporation range or degree is preferably 80 to 95% of the water contained in the solution, preferably a maximum evaporation degree of 85 to 90% of that in the starting solution, e.g. the fermentation solution, water contained.
  • the suspensions contained have a solids content of 20 to 60% by weight, more preferably 30 to 50% by weight, e.g. 40% by weight, and a water content of 30 to 60%, preferably 40 to 50%, in particular for NaKGS, in the suspension.
  • the evaporative crystallization is carried out at low temperatures and under reduced pressure. Gentle reaction conditions prevent the product from decomposing.
  • the temperature in the crystallizer is between 20 ° C and 100 ° C, more preferably between 30 ° C and 80 ° C, most preferably between 40 ° C and 70 ° C.
  • a pressure of 0.01 bar to 1 bar is preferred, more preferred are 0.05 bar to 0.5 bar, most preferred are 0.1 bar to 0.3 bar.
  • the solids content in the crystallizer is preferably 5 to 60% by weight, more preferably 25 to 50% by weight.
  • Solids content in the crystallizer is understood to mean the weight fraction of crystallized salt of an organic acid, in particular Na KGA, based on the total amount of suspension.
  • Evaporation crystallization can be carried out in any crystallizer, e.g. in a stirred tank, forced circulation, guide tube or fluidized bed crystallizer (e.g. Oslo type).
  • the crystallizer is preferably also suitable for carrying out the process under lower pressure.
  • the method according to the invention also comprises vaporization crystallization, which is combined with cooling crystallization.
  • cooling crystallization the fermentation broth is cooled after evaporation with crystallization of the salt of the organic acid. Cooling to 0 ° C. to 50 ° C. is preferred, more preferably 30 ° C. to 40 ° C.
  • the cooling crystallization can be carried out in the same apparatus as the evaporative crystallization. Cooling can be done by vacuum evaporation, direct cooling with a coolant or indirectly via heat exchangers. To avoid incrustation, all types of construction with continuously or recurrently cleaned heat exchanger surfaces can be used, e.g. Cooling disc crystallizers.
  • Crystal yields should also be above 50 to 60% from a product quality point of view lie. Crystal yields of approximately 60 to 90% and an evaporation rate of 75 to 95% are particularly preferred.
  • the concentration of the salt of the organic acid in the starting solution is preferably at least 5%, more preferably 7%, even more preferably 10%, even more preferably 12% or more.
  • the amount of solvent evaporated and the 10 crystallization shares reached depend on the salt concentration in the starting solution.
  • an aqueous 2% Na KGA solution approx. 90% of the solvent (eg water) must be evaporated in order to achieve crystallization, with an aqueous 15% Na KGA solution less than 30% to 50% % of the solvent 15 evaporated.
  • the present invention therefore relates to a method in which the partial evaporative crystallization is carried out under the following conditions:
  • the process is particularly preferably carried out under conditions (i) to (iv). Even more preferably, method 30 is carried out under the following conditions:
  • the crystallization yields are from 60 to 40 90% (w / w) and degrees of evaporation of more than 75% are achieved. It is therefore particularly preferred if the process according to (i) to (iv) is carried out and (v) the initial concentration of Na-KGA is at least 5%.
  • displacement precipitation is achieved by adding an organic solvent which is miscible with water, but in which the salt to be isolated is not or only poorly dissolved to the mother liquor during or after the evaporation crystallization or by adding the mother liquor to the organic solvent.
  • Precipitation is preferably accomplished by the addition of a water-soluble polar solvent, preferably by the addition of a water-soluble alkyl alcohol, e.g. Methanol, ethanol, n-butanol, iso-butanol, 1-propanol, 2-propanol, hexanols, heptanols, octanols etc. or a water-soluble alkyl ketone, e.g. Acetone, 2-butanone, pentanone, etc. achieved, methanol or ethanol is preferred. Most preferred is methanol.
  • a water-soluble polar solvent preferably by the addition of a water-soluble alkyl alcohol, e.g. Methanol, ethanol, n-butanol, iso-butanol, 1-propanol, 2-propanol, hexanols, heptanols, octanols etc. or a water-soluble alkyl
  • the salt is sparingly soluble in the solvent used, preferably almost insoluble.
  • the solubility of the salt is preferably 7%, more preferably 5%, even more preferably less than 3%.
  • the precipitation is preferably carried out with 10 to 80%, more preferably with 15 to 70%, even more preferably with 15 to 60%, most preferably with 20 to 40%, displacement agents with respect to the aqueous solution or the fermentation broth (feed stream) in the reaction vessel, in particular in the case of alkyl alcohols, in particular in the case of ethanol, methanol or propanol.
  • the amount of the displacer depends on the degree of restriction in step (a).
  • the method according to the invention preferably achieves a purity of more than 90% after steps (a) and (b), more preferably more than 95%, even more preferred are 96%, 97%, 98%, 99% or more.
  • the displacement precipitation is carried out at a temperature in the precipitation apparatus from 0 to 100 ° C., preferably at 10 to 80 ° C., particularly preferably at 20 to 70 ° C.
  • the choice of the reaction temperature and the amount of displacement agent depends on the solubility of the salt to be precipitated and of the displacement agent in water.
  • the solubility product of the salt can be selected by the choice of the reaction temperature be influenced in the solution, which affects the amount of displacement agent that is necessary, the desired
  • the precipitation can be carried out in a crystallizer or in arrangements specific to the precipitation with devices for targeted mixing, e.g. with mixing nozzles.
  • the present invention relates to a method in which, according to the invention, the displacement crystallization is carried out under the following parameters:
  • the process is particularly preferably carried out under conditions (i) to (iii).
  • the method is more preferably carried out under the following parameters:
  • Displacement agents ii) Precipitation with 20% to 40% of the fermentation broth; and iii) temperature in the precipitation apparatus from 20 ° C to 60 ° C.
  • Evaporation crystallization and precipitation can be carried out in two separate or in a single apparatus, depending on the temperature and pressure conditions and the choice of the precipitant. Steps (a) and (b) of the method according to the invention can thus be carried out in succession or simultaneously.
  • a high yield is advantageous in only one or possibly in two steps, advantageously of more than 90%, preferably of more than 95%, particularly preferably of more than 97 or 98%, most preferably 99% or more based on the KGA content of the starting fermentation solution (feed solution).
  • the crystals obtained can be washed in order to remove impurities contained therein.
  • the crystals are preferably washed with a solvent in which the salt of the organic acid has a low, preferably no, solubility.
  • the displacement precipitation solvent is preferably used.
  • the yield of the process according to the invention can be increased by recycling washing water. When recycling washing water, the yield depends on the amount of solvent used, e.g. adjustable between 95 to 99%.
  • the amount of solvent used can be between 0.2 to 1 kg per kg of salt.
  • the solvent is methanol or ethanol and the salt to be purified is a KGS salt, preferably Na-KGS.
  • the crystals obtained by the process according to the invention have only slight discolorations. Depending on the procedure and the yield achieved, the crystals are slightly yellow to colorless. The crystals are preferably colorless.
  • a product from the process according to the invention is also advantageously obtained, in particular salts of lactic acid, gulonic acid, KGA or citric acid, which have a very high purity.
  • the organic acid is a carboxylic acid
  • polyhydroxycarboxylic acids are particularly preferred
  • 2-keto-polyhydroxy-Cs-carboxylic acids are more preferred.
  • Organic acids such as ketogulonic acids or lactic acid, citric acid, vanillic acid, idonic acid or gulonic acid are more preferred.
  • ketogulonic acids are 2,4-diketo-D-gulonic acid, 2, 5-diketo-D-gulonic acid, 2-keto-L-gulonic acid, ascorbic acid. Most preferred is 2-keto-L-gulic acid.
  • the process according to the invention can be carried out continuously or batchwise.
  • the organic acid as the sodium, potassium, magnesium, ammonium or calcium salt.
  • the salt of the acid can usually be prepared by adjusting the appropriate pH, for example by adding the bases NH 4 OH / NH 3 , MgO, Mg (OH) 2 , NaOH, NaHC0 3 , Na 2 CO 3 , KOH, KHC0 3 , KC0 3 , CaOH, CaC0 3 , Ca (OH), CaO, or salts of weak organic acids, for example formic acid, acetic acid, etc.
  • Sodium salts are preferred.
  • Calcium can be precipitated and filtered off, for example, by adding sodium carbonate as calcium carbonate or introducing C0 as CaC0 3 .
  • the isolation of the sodium salt of 2-keto-L-gulonic acid is most preferred.
  • the biomass and / or the organic and / or inorganic constituents, apart from the organic acid to be isolated, of the fermentation broth are reduced.
  • the fermentation broth generally consists of insoluble biomass and organic and inorganic contaminants, the inorganic contaminants consisting essentially of metallic cations.
  • insoluble constituents e.g. Biomass such as microorganisms or cell components separated.
  • Solid components can be removed by common solid / liquid separation processes, e.g. by filtration, especially ultrafiltration or microfiltration, or separation, e.g. Skimming, centrifuging or decanting, e.g. in the presence of precipitants or filtration additives, e.g. Polyacrylamides.
  • the fermentation broth can also be demineralized to remove unwanted inorganic ions.
  • Inorganic cations can be separated off, for example, by acidifying the broth or, for example, using a chelator or cation exchanger, preferably a polymeric cation exchanger. Consequently, the method according to the invention comprises one or more filtration steps, in particular a micro- or ultrafiltration of the fermentation broth, the boundary between micro or ultrafiltration is fluent. Generally, the pore size of about 100 ⁇ m is seen to transition from micro to ultrafiltration.
  • the contaminated solution / suspension can be brought into contact with a membrane under pressure and permeate (filtrate) on the back of the membrane at a lower pressure than on the feed side subtracted from.
  • a concentrate (retentate) which contains cells and / or proteins and a purified filtrate (permeate) which contains Na ketogulonate.
  • a relative velocity between the membrane is advantageous by pumping around, mechanical movement of the membrane or stirring units between the membranes
  • a diafiltration step can then be carried out to increase the yield.
  • the concentration of the non-permeable components is kept constant and the product of value is converted into the permeate.
  • the membrane process can be carried out in batch mode by repeated passage of the suspension through the membrane modules or continuously by a single passage through one or more feed and bleed stages connected in series.
  • the ultrafiltration or microfiltration is preferably a filtration 30 1 with a pore size of 200 to 20 ⁇ m, preferably from 100 to 50 ⁇ m or a filtration 2 or 3 with a pore size of 100 ⁇ m to 5 ⁇ m, preferably from 50 to 20 ⁇ m or one Combination of ultrafiltration 1, 2 and / or 3.
  • a pore size of 20 nm corresponds approximately to a separation limit of 35 20 kD, 5 nm corresponds to approximately 10 kD, the separation limit being very dependent on the respective macromolecule and thus a direct assignment of the separation limit and Pore width cannot take place.
  • filtration 1 is carried out after the fermentation
  • filtration 2 is carried out according to the invention after filtration 1 or after the fermentation, but filtration 2 is advantageously carried out after the filtrate from filtration 1 has been concentrated, as described under.
  • a filtration 3 can also be carried out, as described below. It is preferred to carry out as few filtration steps. Consequently, it is particularly preferred to combine a filtration 1 after fermentation with a filtration 2 after concentration of the filtrate from filtration 1. It is more preferred to carry out only filtration 1 or 2, and most preferably to carry out only filtration 1.
  • the separating layers can consist of organic polymers, ceramics, metal or carbon and are stable in the reaction medium and at the process temperature. For mechanical reasons, the separating layers are generally applied to a single-layer or multilayer porous substructure made of the same or also several different materials as the separating layer. Examples are:
  • the membranes can be used in flat, tubular, multi-channel element, capillary or winding geometry, for which the corresponding pressure-resistant modules are available, which allow a separation between retentate and the permeate.
  • the optimal transmembrane pressures between retentate and permeate are essentially dependent on the diameter of the membrane pores or the separation limit (specified in molecular weight units) and the mechanical stability of the membrane, depending on the membrane type, between 1 and 40 bar, for microfiltration e.g. between 1 and 10 bar and with ultrafiltration e.g. between 8 and 40 bar. Higher transmembrane pressures generally lead to higher permeate flows. In the case where the
  • the transmembrane pressure can be adjusted by raising the permeate pressure.
  • the operating temperature depends on the product and membrane stability. It is between 20 and 90 ° C, preferably between 40 and 80 ° C for Na ketogulonate cleaning. Higher temperatures lead to higher permeate flows.
  • a pore diameter of 50 nm is particularly preferred.
  • D-sorbitol can be fermented to L-sorbose in 2-keto-L-gulonic acid via the fermentation.
  • the fermentation process can be aerobic or anaerobic.
  • the microorganisms or cells can be separated before the organic acid is isolated and optionally returned to the fermentation process.
  • Fermentation broth protists e.g. Yeasts, fungi, algae, or other eukaryotic microorganisms, or bacteria or plant or animal cells are used.
  • gluconobacter Pseudomonas, Corynebacterium, Proteus, Citrobacter, Enterobacter, Erwinia, Xanthomonas, Flavobacterium, Acetobacter, Gluconobacter, Aspergillus, or Brevibacterium or mixtures thereof.
  • Homogenates from plant material, animal cells or algae can also be used as
  • the salt concentration of the organic acid is between 1 and 30% in the starting solution of the process described herein.
  • the salts of the organic acids can e.g. Na KGS a lower
  • the fermentation broth or the starting solution preferably has a content
  • the concentration of the salt depends on the nature of the organic acid, the cation and other processes. conditions depend, such as temperature, and selected so that the fermentation broth does not crystallize at RT, ie at 15 ° C to 25 ° C and normal pressure, ie at 980 to 1100 mbar.
  • the fermentation broth can optionally be concentrated before or after the removal of the biomass and other impurities, for example by evaporation or by osmosis, in particular by reverse osmosis, and thus the concentration of the broth can be adapted to the crystallization.
  • this low temperatures preferably 10 C to 90 C ° C.
  • the fermentation broth is preferably carried out before crystallization and after one or more filtration steps. Concentration after filtration 1 is particularly preferred.
  • the method according to the invention comprises one or more further step (s) for separating and / or processing the crystals or the product.
  • Solid-liquid separation processes e.g. Filtering, decanting, suctioning, skimming, and / or centrifuging, i.e. e.g. Separation with the aid of suction filters, rotary filters, belt filters, pusher centrifuges, peeling centrifuges etc.
  • the crystals can be dried and / or ground and then stored or processed.
  • the crystals of the organic acid salt obtained contain water of crystallization which can be removed by further drying steps.
  • 2-keto-L-gulonate can be isolated as a monohydrate.
  • the crystal water can e.g. be removed by further drying under reduced pressure and, if necessary, by heating.
  • the crystals can then be dissolved in water or another polar solvent, e.g. branched or linear aliphatic alcohols with 3 to 7 carbon atoms, in particular methanol, ethanol, n-propanol, isopropanol, butanol, hexanol or heptanol, are added.
  • polar solvent e.g. branched or linear aliphatic alcohols with 3 to 7 carbon atoms, in particular methanol, ethanol, n-propanol, isopropanol, butanol, hexanol or heptanol
  • the crystals can optionally be extracted by methods known to those skilled in the art.
  • the process according to the invention also comprises steps in order to release the purified acid from the isolated salts in one or more further process step (s), this can be achieved in particular by protonating the acid, for example by an ion exchange process step or by an electromembrane process step, for example by membrane electrolysis or electrodialysis.
  • the cation of the salt is exchanged for a proton on the exchange resin and the acid is released in this way.
  • the cations of the salt are e.g. Sodium, potassium, or calcium ions and the ions of the acid are broken down and ion-selective
  • the acid anions react with released or provided protons (H + ) to the free acid, eg KGA or ascorbic acid, while the counter ion reacts with hydroxide ions (0H-) released or made available in parallel to the corresponding base, eg NaOH.
  • electro-membrane process Depending on the ion-selective membrane used and the electrodes used, different embodiments of the electro-membrane process are distinguished.
  • membrane electrolysis charged particles are separated by an ion exchange membrane in an electric field and protons and hydroxide ions are generated on electrodes by water electrolysis.
  • an arrangement of electrodes is also possible, as in the case of electrodialysis with bipolar membranes, in which case the (then bipolar) electrodes replace the bipolar membrane.
  • the protons and the hydroxide ions are generated by an electrically forced water dissociation on a bipolar membrane.
  • a low energy requirement and avoidance of oxidation or reduction of other components of the solution are advantageous if the electrodes are separated from the acid, base or middle chamber by a separate circuit.
  • an organic acid isolated according to the invention which is taken up in water or an aqueous solution, preferably under the influence of an electric field, can be broken down into anion and metallic countercation via one or more ion-selective membrane (s) and spatially separated and by simultaneous generation or provision of Protons and hydroxide ions then the acid released and the corresponding hydroxide getting produced.
  • Electromembrane process steps are described, inter alia, in EP-A-0230 021, WO96 / 41021, US 50747,306, US 4,990,441, and in European Membrane Guide, edited by Mulder, Netherlands, 1997, pages 35 to 38.
  • the multivalent cations are removed from the solution to a content of up to 15 ppm, preferably up to 5 ppm, more preferably up to 3 ppm, most preferably up to 1 ppm.
  • the multivalent ions can advantageously be removed by treating the solution with a chelating ion exchange resin.
  • Multivalent ions are taken to mean divalent or higher, for example three or tetravalent ions, ie cations or anions, for example Ca 2+ , Mg 2+ , C0 3 2_ etc.
  • chelating ion exchange resins for example, those are suitable which carry iminodiacetic acid groups or aminophosphonic acid groups , These are, for example, Amberlite 718 or 748 from Rohm and Haas.
  • the present invention relates to a process for producing a free organic acid from its salt and a corresponding hydroxide of the salt, comprising the isolation of the organic acid according to the invention and further the following steps:
  • the crystallizate solution after step (c) has a concentration of the salt of the organic acid of 10 to 50% by weight, preferably a concentration of 15 to 25% by weight.
  • the method according to the invention can have the following further step
  • the filtration is preferably a filtration 3 which takes place after the crystals have been dissolved after step (c) and / or before the acid release after step (e).
  • Filtration of the crystallizate solution can remove any contaminants that have precipitated, in particular, for example, proteins that would be harmful if the acid were released.
  • the advantage of a filtration 3 is that a lower volume of feed stream compared to the filtration 2 described above has to be cleaned, since the crystallizate solution generally has a higher concentration of the salt of the organic acid. It is also advantageous that some of the impurities are not co-precipitated, so that the feed stream is already pre-cleaned. It is also advantageous that some of the proteins denature and coagulate during crystallization and precipitation in water with alcohol, in particular ethanol or methanol, and the membrane can thus be used better.
  • the membranes described above for example with a pore size of 100 to 5 nm, preferably from 50 to 20 nm, can be used for protein separation. Filtration can be used instead of filtration 2, for example.
  • the acid mentioned is preferably released by means of an electromembrane process, particularly preferably by means of membrane electrolysis or electrodialysis.
  • the protons or hydroxide ions can be generated by electrolysis or on bipolar membranes. It is also advantageous that no additional chemicals have to be used in such a process step.
  • the alkalis can also be obtained as a valuable substance depending on the embodiment.
  • the cation of the dissolved salt (countercation) and / or the anion of the dissolved salt of an organic acid is separated from the crystallizate solution (feed stream for the electromembrane process) by means of one or more ion-selective ion exchange membrane (s) in an electric field.
  • the salt can, for example, be dissolved in water or an aqueous solution.
  • the separation of the anion from other impurities in the feed stream is particularly advantageous. Both ions can also be separated from the feed stream, for example the crystallized solution.
  • the cations and anions of the salt mentioned react with protons and hydroxide ions generated or provided at the same time, so that the free organic acid and the corresponding hydroxide of the countercation are produced.
  • Protons can e.g. by adding acid
  • hydroxide ions can be provided, for example, by adding bases.
  • an anion or cation exchange membrane is consequently placed between a terminal anode and a terminal cathode, so that an anode and a cathode chamber form, the free organic acid in the anode chamber (acid circuit) and in the cathode chamber ( Base circle) the corresponding hydroxide of the counter cation is produced.
  • the cations for example the sodium ions
  • the cations are removed from a chamber through which the crystalline solution flows, under the influence of the electric field. Electroneutrality is maintained in that each sodium ion is replaced by a proton (acid circuit) produced at the anode of the monopolar electrode.
  • the cations migrate across the cation exchange membrane in the direction of the cathode into the cathode or base chamber, which is flushed, for example, by the base to be produced, in order to reduce the conductivity. deliver where they react with the hydroxide ions produced on the cathode of the monoplar electrode to form the corresponding alkali, eg NaOH (base cycle).
  • the cation exchange membrane is exchanged for an anion exchange membrane, the anions of the acid, for example the ketogulonate or, migrate
  • the membrane through the membrane into the anode chamber (acid chamber), which is preferably of a dilute acid, e.g. of the acid to be cleaned is rinsed to produce the conductivity and reacts there with the protons produced on the monopolar electrodes.
  • the cations remain in the feed solution and react with the hydroxide ions produced on the cathode to form the alkali.
  • a disadvantage of the two-chamber system with monopolar electrodes is that only the solution in the base chamber (in the case of a cation exchange membrane) or the solution in the acid chamber (in the case of an anion exchange membrane) is separated from the feed stream and thus cleaned.
  • both the acids to be cleaned and the bases can be separated from the feed stream.
  • Two selective ion exchange membranes are placed between a terminal anode and a terminal cathode, so that an anode, a middle and a cathode chamber are formed, the middle chamber being separated from the cathode chamber by an ion exchange membrane and from the anode chamber by an ion exchange membrane.
  • the ion exchange membranes can be identical or different, i.e. e.g. two anion, two cation or one anion and one cation exchange member (s) can be used.
  • the middle chamber forms the entry chamber and will advantageously be separated from the cathode chamber by a cation exchange membrane and from the anode chamber by an anion exchange membrane.
  • the middle chamber e.g. the crystals solution from step (c) or (d) introduced (feed stream).
  • the ions migrate according to the principle described above.
  • the free acid then forms in the anode chamber and the corresponding base of the counter ion in the cathode chamber.
  • a terminal electrode can be replaced by a bipolar electrode, which then has the same arrangement of the chambers as described above and one follow terminal electrode. The electrolysis takes place in this package on the bipolar electrode.
  • the electrolysis at the terminal electrodes can thus be supplemented by an electrodialysis on a bipolar membrane, which is then followed by the same arrangement of the chambers as in one of the method steps described above and a terminal electrode.
  • the electrodes are preferably flushed through their own circuits. This can be done, for example, by surrounding the electrodes with monopolar membranes, which separate the acid or base circuit from the electrodes, as is shown, for example, in Figures 1 and 2.
  • electrode solutions come acids or bases such as H 2 S0 4 , HN0 3 , NaOH, KOH etc. or solutions of alkali metal salts such as Na 2 SÜ 4 , K 2 SO 4 , NaN0 3 , KN0 3 etc. into consideration.
  • the acid can also be released via a two-chamber gas diffusion anode cell, such as is used e.g. in US 6,004,445.
  • Anion exchange membranes which are strong, mild or weakly basic, selective and permeable to monovalent anions but not to cations can be used in the process according to the invention.
  • the cation exchange membranes can be mild or strongly acidic membranes, which contain, for example, phosphoric acid or sulfonic acid groups, and allow monovalent cations, but no monovalent anions.
  • the bipolar membranes have a cation and an anion exchange layer, the first permeable to cations and the latter permeable to anions. The cation layer does not let anions through and the anion layer does not allow cations. Examples Games of such membrane are listed, for example, in EP-A-779 286, S8, lines 8 to 24.
  • the membrane electrolysis is carried out according to the principle of the electrodialysis shown in Figure 1 or 2, a two-chamber system according to the principle of the electrodialysis shown in Figure 1 is particularly preferred.
  • a solution containing the salt of an organic acid, e.g. Na-KGS, the anion, e.g. Na-KGS by applying an electric field from a diluate or middle chamber through an anion exchange membrane to the acid circuit chamber.
  • the transferred anion, e.g. Na-KGS is converted to the free acid, e.g. by the protons formed on the bipolar membrane.
  • KGS implemented.
  • the counterions of the anion, e.g. Na-KGS sodium ions are transferred through a cation exchange membrane into the base circle chamber and form the corresponding base with the hydroxide ions released there on the bipolar membrane. Uncharged particles remain in the diluate chamber, so that KGS is cleaned up at the same time.
  • a dilute solution of the free acid, e.g. KGS which e.g. can come from the previous batch.
  • Figure 2 illustrates the principle of the process.
  • an electrodialysis step is used, which is characterized in that from the feed solution which contains the salt of the organic acid, e.g. Na ketogulonate (Na-KGS) or other ketocarboxylic acid in an anionic form, and cations, e.g. Na ions, by applying an electric field from the acid circuit chamber through the cation exchange membrane to a base circuit chamber. From the transferred counterions, e.g. Na ions, the corresponding base, e.g. Sodium hydroxide solution, formed and separated or returned in dilute solution. The anion remains in the so-called acid circuit chamber and, together with the protons released there on the bipolar membrane, forms the free acid, in particular KGA.
  • Figure 1 illustrates the principle of the process and is particularly advantageous in combination with the previous crystallization steps according to the invention.
  • the base circuit used for the counterion in the case of sodium salts, for example sodium hydroxide solution
  • the base circuit used for the counterion is used as a base circuit in high dilution; it is only necessary to ensure sufficient ionic conductivity of the solution at the beginning of the electrodialysis become.
  • the base formed can, if necessary after concentration, be used again in the fermentation.
  • the electrodes are rinsed with an electrolyte solution in a separate circuit.
  • packets as described above are e.g. with monopolar electrodes, or with bipolar electrodes or bipolar membranes and the described arrangements of the chambers arranged several times in succession.
  • the 2-chamber packages from the acid and base chamber or the 3-chamber packages from the acid, base and medium or feed chamber can be arranged several times in a row.
  • acid anions and counterions can be separated from one another in several parallel circuits under only one electric field.
  • terminal anode / anode chamber / 1st membrane / cathode chamber / 1st cathode / cathode chamber / 2nd membrane / anode chamber / 2nd anode / anode chamber / ... etc. ... last membrane / last cathode chamber / terminal Cathode exist.
  • Further examples of multiple chambers are described in detail in the literature on electrolysis and electrodialysis cited above, are known to the person skilled in the art and are expressly incorporated herein.
  • the feed solution may contain organic or inorganic salts in order to improve the conductivity of the solution if necessary; for example alkali metal sulfates, bisulfates, chlorides or phosphates, organic acids, e.g. Ammonium tetrabutyl, ammonium salts, e.g. ammonium chloride etc. may be included. It is preferred that the proportion of other salts is low, most preferably that no other salts are added to the feed solution.
  • Homogeneous or heterogeneous, cross-linked or non-cross-linked polymers can be used as bipolar membranes, which have suitable functional groups, such as -S0 3 ⁇ , -C0 2 ⁇ . -NR 4 + etc. are occupied, e.g. Neosepta BP-1 from Tokuyama Corp. or FBI from FuMaTech.
  • Possible cation exchange membranes are, for example, Neosepta CMX and CMB membranes from Tokuyama Corp., Selemion CMV from Asahi Glass or Nafion 350 and 450 from DuPont.
  • Anion exchange membranes can, for example, Neosepta AMX or ACS from Tokuyama Corp. or Selemion AMV or ASV from Asahi Glass.
  • the current density or electrical voltage used in the process according to the invention depends on the process parameters and is in the specialist knowledge of the person skilled in the art or can be real effort.
  • the decisive factors can be the concentration of ions, the type and number of membranes, the arrangement and dimensions of the chamber and the temperature.
  • the membrane electrolysis is preferably carried out in a temperature range from 0 ° C. to 90 ° C. and at current densities of 1 to 1000 mA / cm.2. Since the organic acids, especially KGA and ascorbic acid are sensitive to heat, the lowest possible temperature is chosen, preferably between 10 ° C and 40 ° C. In the case of electrodialysis, the process is carried out at 0 ° C to 60 ° C, preferably between 20 ° C and 40 ° C and at current densities of 1 to 500 mA / cm2, particularly preferably at 50 to 150 mA / cm2. Most preferred are 20 ° C and 40 ° C and 50 to 150 mA / cm2.
  • the release step of the process according to the invention only 60% to 99% degree of release, preferably 80% to 95%, of the free organic acid relative to the total content of the salt of the organic acid in the crystallizate solution or the feed solution of the electromembrane process is released.
  • the acid release by electrodialysis is advantageously not carried out completely, but only up to a degree of release of max. 99%.
  • the remaining counterions generally Na, K
  • the remaining counterions are removed by a conventional cation exchanger or another suitable method for releasing residual acid, e.g. Move with HC1, removed.
  • the use of cation exchangers is preferred.
  • Numerous acidic ion exchange resins known to those skilled in the art e.g. are macroporous or gel-like resins made of cross-linked or non-cross-linked polymers with functional
  • Groups such as -S0 ⁇ or -C0 2 ⁇ , for example Lewatit S2528 or S100 from Bayer AG or Nekrolith RP or RPS from Mitsubishi Chemical Corporation.
  • the acid released can then be crystallized, dried or further processed directly in solution.
  • aqueous KGS can be esterified directly.
  • the dried KGS can then be esterified with an alcohol as described below, advantageously with a -C ⁇ to C 4 alcohol. If the purity of the product is not sufficient, crystallization can be carried out as described above.
  • KGS released by the process according to the invention is advantageously used as an important intermediate for the production of ascorbic acid and can thus contribute significantly to an overall optimum of ascorbic acid production.
  • KGS esters are intermediates in the production of ascorbin acid.
  • free KGA is esterified in industrial processes with a branched or unbranched C ⁇ to Cs alkyl alcohol, for example with methanol, ethanol, n-butanol, isobutanol, 1-propanol, 2-propanol, pentanol, etc.
  • the present invention thus also relates in one embodiment to a process for the preparation of an ester of an organic acid, preferably an ester of 2-keto-L-gulonic acid, in particular the methyl, ethyl or butyl ester of these acids, the process comprising the steps of the method described above and further comprising releasing the acid and esterifying the free acid.
  • the release and esterification can take place according to methods as described above or are described, for example, in the cited EP 0 805 210.
  • the present invention also relates to a process for the production of ascorbic acid, comprising the steps of the process described above and further, one or more of the following steps: lactonizing the KGS and the KGS ester to ascorbic acid, isolating the crude ascorbic acid.
  • the method may also include one of the following further steps:
  • the organic acid is advantageously isolated in the process according to the invention under neutral to alkaline conditions. So side reactions, such as the lactonization of KGS to ascorbic acid, reduced, preferably excluded.
  • the isolation of high-purity 2-keto-L-gulonate for the production of ascorbic acid is advantageously carried out in an early process step before the isolation of the end product ascorbic acid, which leads to lower by-products in the subsequent steps of the process and thus to an improved quality and yield and purity of the end product.
  • the purified acid can be esterified and lactonized as described in the literature.
  • the process product in particular Na-KGS, KGS, ascorbate or ascorbic acid, has a purity of more than 80%, more preferably more than 90%, even more preferably more than 95%, most preferably more than 98% ,
  • the invention is illustrated by the following figures:
  • Figure 1 shows the principle of the release of KGS in bipolar electrodialysis with 2 circuits / 2 chambers. 5
  • Figure 2 shows the principle of the release of KGS in bipolar electrodialysis with 3 circuits / 3 chambers.
  • Example 3 The same experimental setup is carried out under identical conditions as in Example 1, but without the subsequent methanol precipitation. Under these test conditions, Na-KGS monohydrate is obtained as a yellowish-brownish-colored solid with a purity of 98.5% in a yield of only 73%.
  • Example 3
  • a chelating ion-exchange resin for this purpose, 3 kg of the solution described above were passed over a column with a diameter of 3 cm filled with 160 g of Amberlite 718 ion exchange resin. Mg ions were removed from the solution except for a content below 5 ppm.
  • Example 1 The solution obtained in Example 1 was divided into three 1 kg portions. The individual portions were then used to release the acid in the acid circuit of an electrodialysis with bipolar membranes.
  • the electrodialysis module was equipped with 5 Neosepta BP-1 membranes as bipolar membranes, 5 Neosepta CMX membranes as cation exchange membranes and 2 Neosepta C66F membranes as end membranes. Platinum was used as the electrode material.
  • the effective membrane area of a membrane was 37 cm.
  • the spacers between the membranes were 1 mm thick.
  • sulfuric acid was used as the electrolyte.
  • the base circle insert was a 0.5% by weight sodium hydroxide solution (500 g).
  • the three electrodialysis experiments were carried out with a current density limitation of 80 mA / cm2 and a cell voltage limitation of 20 V.
  • the test duration was 1 Vz, 2 and 3 hours in order to achieve different degrees of depletion.
  • the results are documented in the following table.
  • a 14% by weight KGS solution was contained as the acid circuit discharge and an approx. 4% by weight sodium hydroxide solution as the base circuit discharge.
  • the losses to KGS in the base circle were less than 1%.

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Abstract

La présente invention concerne un procédé pour isoler des sels d'acides organiques contenus dans une solution aqueuse, en particulier dans un bouillon de fermentation, par cristallisation partielle par évaporation puis par précipitation par déplacement consécutive ou simultanée desdits sels, ainsi que pour libérer l'acide organique contenu dans la masse cristalline, de préférence par un procédé électromembranaire.
EP02785181A 2001-10-10 2002-10-09 Procede pour separer des sels d'acides organiques contenus dans un bouillon de fermentation et liberer l'acide organique Withdrawn EP1436245A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10149869A DE10149869A1 (de) 2001-10-10 2001-10-10 Verfahren zur Isolierung von Salzen von organischen Säuren aus einer Fermentationsbrühe und zur Freisetzung der organischen Säure
DE10149869 2001-10-10
PCT/EP2002/011306 WO2003033448A1 (fr) 2001-10-10 2002-10-09 Procede pour separer des sels d'acides organiques contenus dans un bouillon de fermentation et liberer l'acide organique

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JP2005151984A (ja) * 2003-11-07 2005-06-16 Mitsubishi Chemicals Corp 有機酸塩の製造方法
EP1686182A1 (fr) * 2003-11-07 2006-08-02 Mitsubishi Chemical Corporation Procede de production d'un sel acide organique
CA2658483A1 (fr) 2006-07-21 2008-01-24 Xyleco, Inc. Systemes de conversion de biomasse
CN101550129B (zh) * 2009-03-06 2012-07-25 天津金牛电源材料有限责任公司 一种精制1,3-丙烷磺内酯的方法
US9919271B2 (en) * 2012-01-30 2018-03-20 Universiteit Gent Electrochemical processes to separate products derived from biological conversions
DE102018000672A1 (de) 2018-01-29 2019-08-14 Rheinisch-Westfälische Technische Hochschule (Rwth) Aachen Verfahren zur Übertragung eines Zielstoffs zwischen zwei flüssigen Phasen
US11453897B2 (en) 2018-06-07 2022-09-27 Covestro Intellectual Property Gmbh & Co. Kg Method for producing aminobenzoic acid or an aminobenzoic acid derivative product
CN111943836A (zh) * 2019-05-16 2020-11-17 帝斯曼知识产权资产管理有限公司 回收2-酮-l-古洛糖酸的改进方法
US20230174450A1 (en) * 2020-06-08 2023-06-08 Entegris, Inc. Process and system for purification of citric acid
CA3212507A1 (fr) * 2021-03-04 2022-09-09 Monsanto Technology Llc Electrodialyse de sels d'acides amines a membrane bipolaire a deux compartiments
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