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EP2504302A1 - Procédé permettant d'isoler un alcanol d'une suspension aqueuse de biotransformation - Google Patents

Procédé permettant d'isoler un alcanol d'une suspension aqueuse de biotransformation

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Publication number
EP2504302A1
EP2504302A1 EP10782283A EP10782283A EP2504302A1 EP 2504302 A1 EP2504302 A1 EP 2504302A1 EP 10782283 A EP10782283 A EP 10782283A EP 10782283 A EP10782283 A EP 10782283A EP 2504302 A1 EP2504302 A1 EP 2504302A1
Authority
EP
European Patent Office
Prior art keywords
alkanol
phase
fraction
solvent
aqueous
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
EP10782283A
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German (de)
English (en)
Inventor
Jürgen Däuwel
Michael Breuer
Bernhard Hauer
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BASF SE
Original Assignee
BASF SE
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Filing date
Publication date
Application filed by BASF SE filed Critical BASF SE
Priority to EP10782283A priority Critical patent/EP2504302A1/fr
Publication of EP2504302A1 publication Critical patent/EP2504302A1/fr
Withdrawn legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
    • C07C29/74—Separation; Purification; Use of additives, e.g. for stabilisation
    • C07C29/76—Separation; Purification; Use of additives, e.g. for stabilisation by physical treatment
    • C07C29/80—Separation; Purification; Use of additives, e.g. for stabilisation by physical treatment by distillation
    • C07C29/82—Separation; Purification; Use of additives, e.g. for stabilisation by physical treatment by distillation by azeotropic distillation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
    • C07C29/74—Separation; Purification; Use of additives, e.g. for stabilisation
    • C07C29/76—Separation; Purification; Use of additives, e.g. for stabilisation by physical treatment
    • C07C29/80—Separation; Purification; Use of additives, e.g. for stabilisation by physical treatment by distillation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
    • C07C29/74—Separation; Purification; Use of additives, e.g. for stabilisation
    • C07C29/76—Separation; Purification; Use of additives, e.g. for stabilisation by physical treatment
    • C07C29/86—Separation; Purification; Use of additives, e.g. for stabilisation by physical treatment by liquid-liquid treatment
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers

Definitions

  • WO 2006/53713 describes a process for the preparation of (S) -butan-2-ol by reduction of butan-2-one in the presence of an alcohol dehydrogenase (ADH) with a specific polypeptide sequence.
  • ADH alcohol dehydrogenase
  • the enantioselective reduction is carried out with the ADH in the presence of a reducing agent, such as glucose or formate, which regenerates the oxidized in the course of the reduction cofactor.
  • a second dehydrogenase e.g. Glucose dehydrogenase or formate dehydrogenase can be added.
  • the biotransformation product is contaminated by lipophilic cell components to a considerable extent, which makes expensive cleaning operations necessary.
  • the prior art usually employs a thermal cleaning process (distillation) to separate the desired product from the lipophilic cell constituents. For steam-volatile compounds, high rates of loss are sometimes observed in this process.
  • the object of the invention is therefore to provide a process for isolating alkanols, in particular optically active alkanols, from an aqueous biotransformation broth, which is adapted to the high dilution of the desired products in the biotransformation broth and manages without long Phasenseparations doctrine in the extraction with organic solvents ,
  • the object is achieved by a process for isolating an alkanol from an aqueous biotransformation broth which comprises a) obtaining a first alkanol phase by distilling off an alkanol-water azeotrope from the aqueous biotransformation broth and, if the azeotrope is a heteroazeotrope, phase separation of the Azeotrope and separation of an aqueous phase,
  • step c) fractionally distilling the second alkanol phase to obtain a pure alkanol fraction.
  • the first alkanol phase has a first water content
  • the second alkanol phase has a second water content.
  • the second water content is lower than the first water content.
  • water content is meant the amount of water, based on the alkanol content.
  • M / 49266-PCT must be drawn, such as a separation of biomass, for example by centrifugation or filtration.
  • azeotrope of 2-butanol and water has a 2-butanol content of about 72% by weight.
  • the boiling point of the azeotrope is at normal pressure at about 87 ° C, well below the boiling points of water and 2-butanol of about 100 ° C.
  • the method is basically applicable to the isolation of any biotransformed alkanol which forms an azeotrope with water.
  • the azeotrope may be a homogeneous azeotrope or heteroazeotrope.
  • the alkanols include C 2 -C 8 alkanols, in particular C 4 -C 8 alkanols, whose alkyl chain may be straight-chain or branched and which may be primary, secondary or tertiary alcohols.
  • the alkanol is preferably selected from optically active alkanols, in particular optically active 2-alkanols. Particularly preferred examples are S-2-butanol, S-2-pentanol and S-2-hexanol.
  • an alkanol-water azeotrope is distilled off from the aqueous biotransformation broth.
  • the apparatus implementation of the distillation is possible in various embodiments.
  • the distillation can be carried out as a simple distillation, i. essentially without material exchange between rising vapor and returning condensate, or be designed as a rectification. For the latter, all known types of distillation or rectification columns, e.g. run below.
  • the vapor containing the alkanol-water azeotrope is at least partially condensed. Suitable for this purpose are any heat exchangers or condensers which may be air-cooled or water-cooled.
  • the first alkanol phase contains dissolved water due to the solubility of water. Before further purification by distillation, the first alkanol phase must therefore be dried. In one embodiment, the drying of the first alkanol phase is carried out by liquid / liquid extraction with a solvent as the extraction agent. Suitable extractants are solvents in which water has only a very low solubility or is substantially insoluble. The water is due to the presence of the extractant, which reduces the solubility of water in the alkanol to be purified, eliminated and forms a separate phase that can be separated.
  • suitable equipment such as a stirred tank, centrifugal extractor, countercurrent extractor and the like.
  • the second alkanol phase obtained as the solvent phase now contains the alkanol dissolved in the solvent with a markedly reduced proportion of water.
  • the first alkanol phase may be subjected to azeotropic drying in the presence of a solvent as an entraining agent. During azeotropic drying, the dissolved water is removed from the system as a water-solvent azeotrope.
  • the solvent suitable as extractant or entraining agent is, for example, aliphatic hydrocarbons, such as pentane, hexane, heptane, cyclohexane, methylcyclohexane; aromatic hydrocarbons, such as benzene, toluene, xylenes; halogenated hydrocarbons, such as dichloromethane, trichloromethane, dichloroethane, chlorobenzene.
  • Aliphatic hydrocarbons, such as in particular n-hexane are particularly preferred because of their comparative non-toxicity and easy separability from the alkanol.
  • the second alkanol phase is then fractionally distilled to give a pure alkanol fraction.
  • the alkanol is freed from the added solvent, unreacted substrate, residual water, by-products and the like.
  • the second alkanol phase is introduced laterally into a fractionation column, the pure alkanol fraction is withdrawn as a side stream, a fraction boiling lower than the alkanol fraction overhead and a fraction boiling higher than the alkanol fraction in the bottom from.
  • the second alkanol phase is distilled discontinuously, successively obtaining a fraction boiling lower than the alkanol fraction, the pure alkanol fraction and a fraction which boils higher than the alkanol fraction.
  • the fraction boiling lower than the alkanol fraction contains the majority of the solvent used and can advantageously be recycled at least partially as solvent to step b).
  • the aqueous biotransformation broth used in the process of the invention is obtained by any biotransformation process which converts a substrate to an alkanol.
  • alkanols are produced by the metabolism of fermentable carbon sources by an alkanol-producing microorganism.
  • Enzymatic production is the selective chemical conversion of defined pure substances (educts) into products by enzymes, wherein the enzymes may be present in living, dormant or disrupted cells or may be enriched or isolated. a) Fermentative production of alkanols
  • WO 2008/137403 describes a process for the preparation of 2-butanol by fermentation.
  • suitable natural or recombinant, pro- or eukaryotic microorganisms for fermentative production are those which, under aerobic or anaerobic conditions, can be used for the fermentative production of the desired Al species.
  • bacteria are to be mentioned, which are selected from bacteria of the families Enterobacteriaceae, Pseudomonadaceae, Bacillaceae, Rhizobiaceae, Clostridiaceae, Lactobacillaceae, Streptomycetaceae, Rhodococcaceae, Rhodocyclaceae and Nocardiaceae.
  • suitable genera include in particular Escherichia, Streptomyces, Clostridium, Corynebacterium and Bacillus.
  • Suitable fermentation conditions, media, fermenters and the like are determinable by one skilled in the art within the scope of his general knowledge. For this he can, for example, the embodiments in suitable technical literature, such. Rehm et al, Biotechnology, Vol. 3 Bioprocessing, 2nd ed., (Verlag Chemie, Weinheim).
  • the microorganisms can be cultivated continuously, with and without recycling of the biomass, or batchwise in the batch process (batch culturing) or in the fed batch (feed process) or repeated fed batch process (repetitive feed process).
  • the fermentation can be carried out in stirred fermenters, bubble columns and loop reactors.
  • the culture medium to be used must suitably satisfy the requirements of the respective strains. Descriptions of culture media of various microorganisms are contained in the Manual of Methods for General Bacteriology of the American Society for Bacteriology (Washington D.C, USA, 1981).
  • These media which can be used according to the invention usually comprise one or more carbon sources, nitrogen sources, inorganic salts, vitamins and / or trace elements.
  • Preferred carbon sources are sugars, such as mono-, di- or polysaccharides.
  • Very good sources of carbon are, for example, glucose, fructose, mannose, galactose, ribose, sorbose, ribulose, lactose, maltose, sucrose, raffinose, starch or cellulose.
  • Sugar can also be added to the media via complex compounds such as molasses or other by-products of sugar refining. It may also be advantageous to add mixtures of different carbon sources.
  • Other possible sources of carbon are oils and fats such. Soybean oil, sunflower oil, peanut oil
  • sulfur source inorganic sulfur-containing compounds such as sulfates, sulfites, dithionites, tetrathionates, thiosulfates, sulfides but also organic sulfur compounds, such as mercaptans and thiols can be used.
  • Phosphoric acid potassium dihydrogen phosphate or dipotassium hydrogen phosphate or the corresponding sodium-containing salts can be used as the phosphorus source.
  • Chelating agents can be added to the medium to keep the metal ions in solution.
  • Particularly suitable chelating agents include dihydroxyphenols, such as catechol or protocatechuate, or organic acids, such as citric acid.
  • All media components are sterilized either by heat (20 min at 1, 5 bar and 121 ° C) or by sterile filtration.
  • the components can either be sterilized together or, if necessary, sterilized separately. All media components may be present at the beginning of the culture or added randomly or in batches as desired.
  • the temperature of the culture is usually between 15 ° C and 45 ° C, preferably 25 ° C to 40 ° C and can be kept constant or changed during the experiment.
  • the pH of the medium should be in the range of 5 to 8.5, preferably around 7.0.
  • the pH for cultivation can be controlled during cultivation by addition of basic compounds such as sodium hydroxide, potassium hydroxide, ammonia or ammonia water or acidic compounds such as phosphoric acid or sulfuric acid.
  • foam anti-foaming agents such as. As fatty acid polyglycol, are used.
  • suitable selective substances such as e.g. As antibiotics, are added.
  • oxygen or oxygen-containing gas mixtures such. B. ambient air, registered in the culture.
  • the temperature of the culture is usually 20 ° C to 45 ° C.
  • the culture is continued until a maximum of the desired product has formed. This goal is usually reached within 10 hours to 160 hours.
  • the fermentation broth containing the alkanol can either be fed directly to the further processing according to the invention.
  • first biomass for example, separated by centrifugation or filtration and optionally washed and combined the washing liquid with the alkanol phase.
  • the fermentation broth can be pretreated, for example, the biomass of the broth can be separated.
  • Methods of separating the biomass are known to those skilled in the art, e.g. Filtration, sedimentation and flotation. Consequently, the biomass can be separated, for example, with centrifuges, separators, decanters, filters or in flotation apparatus. For complete recovery of the desired product is often recommended washing the biomass, z. B. in the form of a diafiltration.
  • the choice of method is dependent on the biomass fraction in the fermenter broth and the properties of the biomass, as well as the interaction of the biomass
  • the fermentation broth may in one embodiment be sterilized or pasteurized. b) Enzymatic production of alkanols
  • the preparation of the alkanol is carried out in preferred embodiments by reduction of an alkanone in the presence of an alcohol dehydrogenase.
  • a biotransforming broth containing 2-butanol is obtained by reduction of butan-2-one in the presence of an alcohol dehydrogenase (ADH) (EC 1 .1.1 .1).
  • ADH alcohol dehydrogenase
  • the hydride ions are derived from cofactors, e.g. NADPH or NADH (reduced nicotinamide adenine dinucleotide phosphate or reduced nicotinamide adenine dinucleotide). Since these are very expensive compounds, they are added only in catalytic amounts of the reaction. The reduced cofactors are usually regenerated during the reaction by a concurrent, second redox reaction.
  • cofactors e.g. NADPH or NADH (reduced nicotinamide adenine dinucleotide phosphate or reduced nicotinamide adenine dinucleotide). Since these are very expensive compounds, they are added only in catalytic amounts of the reaction. The reduced cofactors are usually regenerated during the reaction by a concurrent, second redox reaction.
  • the ADH is for example selected from dehydrogenases from microorganisms of the genus Clostridium, Streptomyces or Escherichia.
  • the ADH can be used in purified or partially purified form or else in the form of the microorganism itself.
  • Methods for recovering and purifying dehydrogenases from microorganisms are known to those skilled in the art, e.g. from K. Nakamura & T. Matsuda, "Reduction of Ketones" in K. Drauz and H. Waldmann, Enzymes Catalysis in Organic Synthesis 2002, Vol. IM, 991-1032, Wiley-VCH, Weinheim. Recombinant methods for generating dehydrogenases are also known, for example from W.
  • the reduction is carried out with the ADH in the presence of a suitable cofactor.
  • cofactors for the reduction of the ketone is usually NADH and / or NADPH.
  • ADH can be used as cellular systems that inherently contain cofactors or alternative redox mediators are added (A.
  • reaction takes place with simultaneous or delayed regeneration of the cofactor consumed during the reaction.
  • Regeneration can be carried out enzymatically, electrochemically or electroenzymatically in a manner known per se (Biotechnology Progress, 2005, 21, 1992, Biocatalysis and Biotransformation, 2004, 22, 89, Angew Chem Chem Ed Engl., 2001, 40, 169 Biotechnol Bioeng, 2006, 96, 18; Biotechnol Adv., 2007, 25, 369; Angew.Chem Int. Ed Engl., 2008, 47, 2275; Current Opinion in Biotechnology, 2003, 14, 421; Current Opinion in Biotechnology, 2003, 14, 583).
  • the reduction with the ADH preferably takes place in the presence of a suitable reducing agent which regenerates the cofactor oxidized in the course of the reduction.
  • suitable reducing agents are sugars, in particular hexoses, such as glucose, mannose, fructose, and also formate, phosphite or molecular hydrogen.
  • oxidizable alcohols in particular ethanol, propanol or inexpensive secondary alcohols such as, for example, / -propanol (so-called sacrificial alcohols) can occur as the final hydride donor of the reaction.
  • a regenerating enzyme may be added, such as a second dehydrogenase, e.g. Glucose dehydrogenase (GDH) (EC 1 .1 .1 .47) when using glucose as reducing agent, formate dehydrogenase (EC 1 .2.1.2 or EC 1 .2.1 .43) when using formate as reducing agent or phosphite dehydrogenase ( EC 1.20.1 .1) when using phosphite as a reducing agent.
  • GDH Glucose dehydrogenase
  • GDH Glucose dehydrogenase
  • formate dehydrogenase EC 1 .2.1.2 or EC 1 .2.1 .43
  • phosphite dehydrogenase EC 1.20.1 .1 when using phosphite as a reducing agent.
  • the aqueous reaction media are preferably buffered solutions which generally have a pH of from 5 to 8, preferably from 6 to 8.
  • the aqueous solvent may also contain at least one water-miscible organic compound, such as isopropanol, n-butanol.
  • Suitable buffers include, for example, ammonium, alkali or alkaline earth metal phosphate buffer, or carbonate buffer, or TRIS / HCI buffer, used in concentrations of about 10 mM to 0.2 M.
  • the enzymatic reduction is generally carried out at a reaction temperature below the deactivation temperature of the dehydrogenase used and above
  • M / 49266-PCT from -10 ° C. It is particularly preferably in the range from 0 to 100 ° C, in particular from 15 to 60 ° C and especially from 20 to 40 ° C, for example at about 30 ° C.
  • the biotransformation can be carried out in stirred reactors, bubble columns and loop reactors.
  • stirred reactors bubble columns and loop reactors.
  • a detailed overview of the possible designs including stirrer shapes and geometrical designs can be found in "Chmiel: Bioprocessing Technology: Introduction to Bioprocess Engineering, Volume 1". In the process management are typically the following, known in the art or z. B. in “Chmiel, Hammes and Bailey: Biochemical Engineering” variants explained, such as batch, fed-batch, repeated fed-batch or even continuous fermentation with and without recycling of the biomass available.
  • fumigation with air, oxygen, carbon dioxide, hydrogen, nitrogen or appropriate gas mixtures can / must be carried out in order to achieve good yields.
  • the enzymatic reaction can also be carried out in a manner known from the literature, continuously or discontinuously, as described above for the fermentation.
  • concentrations for substrate, enzymes, reduction equivalents and sacrificial compound can be readily determined by one skilled in the art.
  • WO 2006/53713 describes a process for preparing (S) -butan-2-ol by reducing butan-2-one in the presence of an alcohol dehydrogenase (ADH) having a specific polypeptide sequence.
  • ADH alcohol dehydrogenase
  • the enantioselective reduction is preferably carried out with the ADH in the presence of a reducing agent, such as glucose or formate, which regenerates the cofactor oxidized in the course of the reduction.
  • a second dehydrogenase e.g. Glucose dehydrogenase or formate dehydrogenase.
  • the butan-2-one is preferably used in a concentration of 0.1 g / l to 500 g / l, more preferably from 1 g / l to 50 g / l in the enzymatic reduction and can be followed continuously or discontinuously ,
  • the butan-2-one with the ADH, the solvent and optionally the cofactors optionally present a second dehydrogenase for the regeneration of the cofactor and / or other reducing agents and mix the mixture, z. B. by stirring or shaking.
  • a second dehydrogenase for the regeneration of the cofactor and / or other reducing agents and mix the mixture, z. B. by stirring or shaking.
  • immobilize the dehydrogenase (s) in a reactor for example in a column, and to pass through the reactor a mixture containing the butan-2-one and optionally cofactors and / or cosubstrates.
  • the mixture can be circulated through the reactor until the desired conversion is achieved.
  • the keto group of butan-2- ⁇ is reduced to an OH group, wherein essentially the (S) -enantiomer of the alcohol is formed.
  • the keto group of butan-2- ⁇ is reduced to an OH group, wherein essentially the (S) -enantiomer of the alcohol
  • M / 49266-PCT the reduction to a conversion of at least 70%, particularly preferably of at least 85% and in particular of at least 95%, based on the butane-2- ⁇ contained in the mixture.
  • the progress of the reaction ie the sequential reduction of the ketone, can be monitored by conventional methods such as gas chromatography or high pressure liquid chromatography.
  • WO 2005/108590 discloses a process for the preparation of optically active alkanols which comprises, in an alkanone-containing medium, an enzyme (E) selected from the classes of dehydrogenases, aldehyde reductases and carbonyl reductases incubated in the presence of reducing equivalents, wherein the reducing equivalents consumed in the course of the reaction are regenerated by reacting a sacrificial alcohol to the corresponding sacrificial ketone with the aid of the enzyme (E).
  • E enzyme selected from the classes of dehydrogenases, aldehyde reductases and carbonyl reductases incubated in the presence of reducing equivalents, wherein the reducing equivalents consumed in the course of the reaction are regenerated by reacting a sacrificial alcohol to the corresponding sacrificial ketone with the aid of the enzyme (E).
  • E enzyme selected from the classes of dehydrogenases, aldehyde reductases and carbonyl reduct
  • the enzymes used for alkanol production can be used freely or immobilized in the methods described herein.
  • An immobilized enzyme is an enzyme which is fixed to an inert carrier.
  • Suitable support materials and the enzymes immobilized thereon are known from EP-A-1 149849, EP-A-1 069 183 and DE-OS 100193773 and from the references cited therein. The disclosure of these documents is hereby incorporated by reference in its entirety.
  • Suitable support materials include, for example, clays, clay minerals such as kaolinite, diatomaceous earth, perlite, silica, alumina, sodium carbonate, calcium carbonate, cellulose powder, anion exchange materials, synthetic polymers such as polystyrene, acrylic resins, phenolformaldehyde resins, polyurethanes and polyolefins such as polyethylene and polypropylene.
  • the support materials are usually used to prepare the supported enzymes in a finely divided, particulate form, with porous forms being preferred.
  • the particle size of the carrier material is usually not more than 5 mm, in particular not more than 2 mm (grading curve).
  • Support materials are e.g. Ca alginate, and carrageenan.
  • Enzymes as well as cells can also be cross-linked directly with glutaraldehyde (cross-linking to CLEAs). Corresponding and further immobilization processes are described, for example, in J. Lalonde and A. Margolin "Immobilization of Enzymes" in K. Drauz and H. Waldmann, Enzyme Catalysis in Organic Synthesis 2002, Vol. III, 991-1032, Wiley-VCH, Weinheim. Further information on biotransformations
  • M / 49266-PCT NEN and bioreactors for carrying out the process according to the invention are also found, for example, in Rehm et al. (Ed) Biotechology, 2nd Edn, Vol. 3, Chapter 17, VCH, Weinheim.
  • the contents of the kettle were stirred at an internal temperature of 25 ° C. for a further 24 hours.
  • the pH was kept at pH 6.3-6.7 by addition of 20% NaOH.
  • the reaction solution was stirred for a further 2h at 25 ° C.
  • reaction effluent from the enzymatic reduction was heated in the 16 m 3 stirred tank at atmospheric pressure to about 100 ° C internal temperature.
  • reaction effluent from the enzymatic reduction was heated in the 16 m 3 stirred tank at atmospheric pressure to about 100 ° C internal temperature.
  • product-containing upper phase were separated via a phase separator, while the aqueous phase was recycled to the stirred tank.
  • the break-off criterion for this step was the end of the two-phase distillation of the distillate.
  • the reaction effluent from the enzymatic reduction was heated in a 41-miniplantreaktor at atmospheric pressure to about 100 ° C internal temperature.
  • a single-stage distillation about 140 g of product-containing upper phase were separated off via a phase separator, while the aqueous phase was returned to the reactor. Stop criterion for this step was the end of the two-phase distillate. After reaching this criterion, in addition about 30 g of single-phase distillate were distilled off in order to achieve complete separation of the S-2-butanol from the reaction effluent. The yield in this step was more than 90%.
  • the hydrous S-2-butanol fraction from the azeotropic distillation was admixed with about 100 ml of n-hexane and extracted at room temperature. After phase separation, about 60 ml of an aqueous lower phase and about 240 ml of an organic upper phase were obtained. The water content of the upper phase was reduced by the hexane extraction to less than 5%. The yield in this step was more than 95%.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

L'invention concerne un alcanol qui est isolé d'une suspension aqueuse de biotransformation a) par l'obtention d'une première phase alcanolique en distillant un azéotrope alcanol-eau à partir de la suspension aqueuse de biotransformation et, si l'azéotrope est un hétéroazéotrope, en procédant à une séparation de phases de l'azéotrope et en séparant une phase aqueuse, b) par l'obtention d'une seconde phase alcanolique par (i) extraction liquide/liquide de la première phase alcanolique à l'aide d'un solvant comme agent d'extraction ; ou par (ii) un séchage azéotropique de la première phase alcanolique en présence du solvant utilisé comme agent entraîneur, et c) par une distillation fractionnée de la seconde phase alcanolique tout en conservant une fraction alcanolique pure. La suspension de biotransformation est par exemple obtenue par réduction d'une alcanone en présence d'un alcool déshydrogénase. Le procédé est adapté à la forte dilution des produits finaux dans la suspension de biotransformation et ne nécessite pas de longs temps de séparation de phases lors de l'extraction à l'aide de solvants organiques.
EP10782283A 2009-11-24 2010-11-24 Procédé permettant d'isoler un alcanol d'une suspension aqueuse de biotransformation Withdrawn EP2504302A1 (fr)

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Application Number Priority Date Filing Date Title
EP10782283A EP2504302A1 (fr) 2009-11-24 2010-11-24 Procédé permettant d'isoler un alcanol d'une suspension aqueuse de biotransformation

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EP09176942 2009-11-24
EP10782283A EP2504302A1 (fr) 2009-11-24 2010-11-24 Procédé permettant d'isoler un alcanol d'une suspension aqueuse de biotransformation
PCT/EP2010/068139 WO2011064259A1 (fr) 2009-11-24 2010-11-24 Procédé permettant d'isoler un alcanol d'une suspension aqueuse de biotransformation

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EP2438179B1 (fr) 2009-06-04 2016-12-21 Basf Se Procédé de réduction enzymatique d'énoates
US20130273619A1 (en) 2012-04-16 2013-10-17 Basf Se Process for the Preparation of (3E, 7E)-Homofarnesol
US10399004B2 (en) * 2016-09-08 2019-09-03 Eastman Chemical Company Thermally integrated distillation systems and processes using the same
CA3053708C (fr) * 2017-02-23 2023-12-05 Sappi Biotech Uk Limited Procede de traitement d'hemicellulose

Family Cites Families (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4582570A (en) * 1981-07-24 1986-04-15 Merix Corporation Azeotropic dehydration distillation process
JP3574682B2 (ja) * 1993-09-24 2004-10-06 ダイセル化学工業株式会社 新規な酵素、該酵素を製造する方法、該酵素をコードするｄｎａ、該ｄｎａを含む形質転換体、該酵素による光学活性アルコール等の製造方法
US5763694A (en) * 1997-07-14 1998-06-09 Berg; Lloyd Separating 3-methyl-1-butanol from 1-pentanol by azeotropic distillation
DE19931847A1 (de) 1999-07-09 2001-01-11 Basf Ag Immobilisierte Lipase
DE10019373A1 (de) 2000-04-18 2001-10-31 Pfreundt Gmbh & Co Kg Vorrichtung und Verfahren zur Steuerung eines Maschinenbauteils
DE10019380A1 (de) 2000-04-19 2001-10-25 Basf Ag Verfahren zur Herstellung von kovalent gebundenen biologisch aktiven Stoffen an Polyurethanschaumstoffen sowie Verwendung der geträgerten Polyurethanschaumstoffe für chirale Synthesen
US6623604B1 (en) * 2000-06-05 2003-09-23 Cognis Corporation Method of recovering free fatty acids having low ester content and high acid value
US20050089979A1 (en) 2003-09-18 2005-04-28 Ezeji Thaddeus C. Process for continuous solvent production
JP2005281255A (ja) * 2004-03-30 2005-10-13 Mitsubishi Chemicals Corp 精製アルコールの製造方法
DE102004022686A1 (de) 2004-05-05 2005-11-24 Basf Ag Verfahren zur Herstellung optisch aktiver Alkohole
DE102004055508A1 (de) 2004-11-17 2006-06-01 Basf Ag Verfahren zur Herstellung optisch aktiver Alkohole
JP4744916B2 (ja) * 2005-04-14 2011-08-10 株式会社カネカ 光学活性アルキルアルコール誘導体の単離取得方法
AT502395B1 (de) * 2005-07-27 2007-03-15 Iep Gmbh Oxidoreduktasen zur stereoselektiven reduktion von ketoverbindungen
US8956850B2 (en) * 2008-06-05 2015-02-17 Butamax Advanced Biofuels Llc Enhanced pyruvate to acetolactate conversion in yeast
CN101003779B (zh) * 2007-01-18 2011-05-11 清华大学 Co2循环气提在线分离耦合制备乙醇的方法及设备
US8426174B2 (en) 2007-05-02 2013-04-23 Butamax(Tm) Advanced Biofuels Llc Method for the production of 2-butanol
CN101085992A (zh) * 2007-06-28 2007-12-12 周彦春 野生植物淀粉资源如橡子淀粉替代粮食生产乙醇的办法
BRPI0821519A2 (pt) * 2007-12-27 2015-06-16 Gevo Inc Recuperação de alcoois superiores a partir de soluções aquosas diluída
WO2010151832A1 (fr) * 2009-06-26 2010-12-29 Gevo, Inc. Récupération d'alcools supérieurs à partir de solutions aqueuses diluées

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2011064259A1 *

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