WO2010037807A1

WO2010037807A1 - Method for producing polycarboxylic acid alkyl esters

Info

Publication number: WO2010037807A1
Application number: PCT/EP2009/062743
Authority: WO
Inventors: Andreas Krebs; Bernd Schäfer; Aline Raddatz; Wolfgang Siegel; Katja Bergmann
Original assignee: Basf Se
Priority date: 2008-10-01
Filing date: 2009-10-01
Publication date: 2010-04-08

Abstract

The invention relates to a novel method for producing polycarboxylic acid alkyl esters by reactive extraction of a salt of a polycarboxylic acid from an aqueous solution. The invention also relates to a method for extracting the polycarboxylic acid from the ester produced in this way.

Description

Process for the preparation of polycarboxylic acid alkyl esters

The present invention relates to a novel process for the preparation of polycarboxylic acid polyalkyl esters by reactive extraction from an aqueous solution of a salt of a polycarboxylic acid and to a process for recovering the polycarboxylic acid from the ester thus produced.

Background of the invention

Organic carboxylic acids and their esters are important starting materials for chemical synthesis. It is of particular economic importance to produce such organic carboxylic acids and their esters as inexpensively as possible.

The fermentative production of carboxylic acids using suitable microorganisms is becoming increasingly important. A disadvantage of these methods, however, is that the carboxylic acids are usually not obtained as a pure substance and also not in the form of the free acid but partially or completely neutralized in salt form. Neutralization is usually necessary because otherwise the fermentation broth would become acidified with increasing fermentation time and as a result the microorganism would be damaged. The pure representation of fermentatively but also chemically synthesized carboxylic acids or the corresponding esters is therefore of great importance.

Starting from fermentatively produced carboxylic acids, such as, in particular, lactic acid or succinic acid, a wide variety of value products can be obtained by chemical means with the aid of various synthesis strategies (see, for example, reviews by Varadarajan et al., Biotechnol., Prog., 1999, 15, 845-854).

The esterification of succinic acid in an aqueous medium is described, for example, in Clark et al. Chem. Eur. J. 2007, 13, 6914-6919. In the method described there, however, no organic phase is added. Furthermore, work is carried out in a 2.6-fold volume excess of ethanol to water.

The esterification of succinates from fermentative sources is described in EP-A-1 842 843. The diammonium salt of succinic acid can be esterified with butanol by removing water. In the distillative removal of water can ammonia be recovered as base. The disadvantage of this variant is the limitation to butanol as the smallest alcohol. Furthermore, a complete removal of the water is necessary.

WO-A-98/51567 describes the esterification of fermentatively obtained citric acid. For this purpose, after purification by removal of salts in one example ethanol is used as the alcohol. Butanol is used in the other examples. A disadvantage of the local technical teaching is that for a complete reaction also water must be removed by distillation.

US 2005/0143599 describes the esterification of monoacid with diols. For this purpose, the acid is dissolved in water and the mostly nonpolar alcohol in toluene. The esterification of diacid with monoalcohols is not described. Furthermore, only small amounts of water are present during the esterification, obviously not to shift the equilibrium of the esterification reaction too much to the educt side.

The mono- or multistage esterification of free mono-, di- or polycarboxylic acids by reacting a carboxylic acid / alcohol mixture in a reactor is described in WO-A-2005/051885. However, there is no indication of the use of a second organic phase to favor esterification in the presence of water.

The provision of ester-containing fuels and chemicals from biomass by reacting biologically produced alcohols, in particular methanol and ethanol, and fermentatively produced carboxylic acids is described by Olson et al. in Applied Biochemistry and Biotechnology, 2003, Vol. 105-108, 843-851. Various methods for the preparation of monocarboxylic acid esters are discussed. The successful esterification of polycarboxylic acid salts is not described in this document.

None of the cited documents is concerned with the selective esterification of acid in the presence of an organic phase and of larger amounts of water. Since the presence of water in the esterification is counterproductive, this is usually removed by distillation from the mixture. But this is associated with a great deal of energy.

The present invention is therefore based on the object to provide an improved process for the preparation of polycarboxylic acid esters from the corresponding salts, which on the one hand ensures a high ester yield and on the other hand, the distillative Removal of water no longer needed.

figure description

FIG. 1 shows an example of a continuously operated multi-stage reactive extraction plant.

FIG. 2 shows an overview of the work-up concept of a fermentation output for isolating the valuable product succinic acid dimethyl ester and the possibility of subsequently hydrolyzing this ester to give the free acid.

Summary of the invention

The above object has surprisingly been achieved by providing a process for the preparation of a polycarboxylic acid ester, in which a reactive extraction is carried out by contacting a template comprising an aqueous solution of a salt of the polycarboxylic acid with an alkanol and optionally a catalyst of the esterification brings and resulting from the reaction product by extraction into an organic phase removed from the reaction mixture.

By following the teaching of the invention, it is surprisingly possible to provide the desired polycarboxylic acid ester in a significantly improved yield and surprisingly high purity. Thus, total esterification yields of from 70 to 100%, such as e.g. 80 to 95% based on the amount of carboxylic acid used can be achieved. In addition, removal of water from the reaction mixture is not necessary to produce the desired reaction product in the indicated, surprisingly high yields.

In particular, in addition, the content of undesired coloring components in the product can be significantly reduced by subsequent distillation of the dimethyl ester, so that either the dimethyl ester directly or after appropriate hydrolysis, the dicarboxylic acid can be used in color-sensitive applications, creating a pure representation of the free polycarboxylic acid in this way also surprisingly easy to succeed on an industrial scale.

Detailed description of the invention

1. Preferred Embodiments of the Invention: A first subject of the invention relates to a process for preparing at least one carboxylic acid alkyl ester, in particular a polyalkyl ester of a polycarboxylic acid, such as a dialkyl dicarboxylate, wherein a reactive extraction is carried out by reacting an aqueous solution comprising a salt of at least one water-soluble polycarboxylic acid with a water-soluble alkanol in particular Alkanmonool, in the presence of an esterification catalyst, in an at least two-phase, aqueous-organic solvent system, eg. B. comprising toluene as organic water-insoluble solvent or extractant, for example, in cocurrent or in countercurrent, brings in contact, performs the esterification reaction, substantially without removal of water, and at least one Polycarbonsäurepolyalkylester-containing organic extract phase separated from the reaction mixture , Since the reaction mixture is agitated (eg stirred) in the reactor during the reaction, it is expedient to carry out a phase separation in a manner known per se prior to separation of the extract phase. The separation takes place in particular with increased selectivity, wherein the precursors of the polyester (such as in the case of succinic acid dimethyl ester of monoesters and succinic acid) remain mainly in the aqueous phase.

"Water-soluble" in the context of the invention are compounds (alkanols, polycarboxylic acids) if these can be completely or partially dissolved in an aqueous reaction medium and / or water according to the invention. Water solubility is thus also present if the compound is less in a defined volume of the reaction medium than 100%, less than 90%, 80%, 50%, 25%, 10%, but at least for example to about 1% or 5%, each based on a given amount, can be solved.

"Water Insoluble" is a compound such as the organic solvent for extraction when less than 20% soluble in the aqueous reaction medium and / or water.

"Water solubility" and "water insolubility" are data based on standard conditions: p = 1 bar, T = 25 ° C, pH = 7.

If appropriate, the resulting organic extract phases are further worked up by first removing the organic solvent by distillation and then removing the contained polycarboxylic acid ester overhead by distillation. In contrast to the prior art discussed above, it is thus avoided from the beginning to remove the water to a large extent or even completely from the reaction mixture or its constituents, such as the fermentation effluent containing carboxylic acid salt.

In a particular embodiment of the process according to the invention, the at least biphasic, aqueous-organic system is either formed only after the start of the esterification reaction or is present during the entire course of the esterification reaction.

The at least biphasic, e.g. two-phase or three-phase, aqueous-organic system is formed by adding a water-immiscible organic liquid extractant, wherein the desired polyester is enriched in at least one organic phase thereof.

In particular, according to the invention, the extractant is chosen such that it selectively removes the desired polycarboxylic acid polyalkyl esters from the aqueous phase of the reaction mixture.

A "selective" extraction agent in the context of the invention effects a "selective" extraction, in particular of a polycarboxylic acid polyester prepared according to the invention, in particular a completely esterified polycarboxylic acid, which dissolved better after adjusting the distribution equilibrium between aqueous and organic phases in the organic phase (s) is at least one partially esterified and optionally the unesterified precursor thereof. In particular, the desired polyester, based on the total content of the respective polyester in the reaction mixture in the organic phase (s) to more than about 50 mol .-%, such. B, 51 to 100% or 55 to 99% or 60 to 98% or 65 to 95% mol .-%. At least one, preferably all lower esterification level precursors (i.e., partial esters or unesterified precursors) should be less than about 50 mole percent in the organic phase (s), e.g. 49 to 0% or 40 to 0.01 or 30 to 0, 1 or 20 to 0, 1 or 10 to 0.5 mol .-%, in each case based on the total content of the respective precursor in the reaction mixture, be contained.

Depending on the particular reactants used and the reaction conditions set, the person skilled in the art will select the optimum solvent in each case in order to achieve the desired selectivity in the polycarboxylic acid extraction. Thus, one can in principle use as an extraction agent is a water-immiscible organic solvent is selected from cyclic compounds, in particular aromatic or non-aromatic cyclic, optionally mono - or polyunsaturated, C ₅ - C ₂ - hydrocarbons; and non-cyclic compounds selected from saturated and mono- or polyunsaturated saturated, branched or unbranched C ₅ - C ₂ - hydrocarbons; aliphatic C ₄ - C ₈

Ethers, aromatic ethers, and esters of aliphatic C 1 -C ₆ -monocarboxylic acids with C 1 -C ₈ -monoalkanols; and the mono- or polyhalogenated analogs of these types of compounds.

Without being limited thereto, particularly suitable cyclic solvents are monocyclic aromatic compounds having 5 to 7 carbon atoms, such as toluene and xylene.

Without being limited thereto, particularly suitable non-cyclic solvents are those having 5 to 7 carbon atoms, such as pentane, hexane, heptane; and ethyl acetate of Ci - C ₄

- monoalkanols, to name.

In particular, in the method according to the invention, the volume ratio of aqueous phase (comprising water, polycarboxylic acid and alkanol) to organic (organic) extract phase (s) in the range of about 10: 1 to 0.1: 1, such as. about 10: 1 to 1: 1 or 8: 1 to 4: 1 or 2: 1 to 1: 1.

If appropriate, the process according to the invention can be carried out by repeating the extraction until substantially no further polycarboxylic acid polyester can be extracted from the reaction mixture. So you can the extraction step, e.g. at least once, e.g. 1 to 10 times, in particular. Repeat 1, 2, 3, 4 or 5 times by adding again the water-immiscible organic extractant to the remaining reaction mixture, the esterification reaction still proceeding, and further polycarboxylic acid polyalkyl ester-containing organic extract phase as described above removed from the reaction mixture, optionally combined with the extract phase (s) previously obtained and optionally further processed.

The polycarboxylic acid salt used in the esterification process according to the invention can be prepared either chemically, enzymatically or microbiologically (by fermentation). In particular, it is an optionally prepurified and / or concentrated fermentation broth containing one or more polycarboxylic acid salts. The fermentation broth may also contain free acid or partially neutralized salts, and for reaction, these may be partially or completely neutralized by the addition of bases. Suitable fermentation broths are derived, for example, from the cultivation of a pentoses and / or hexoses and / or polyols, in particular glucose-fermenting and / or glycerol-fermenting microorganisms. The polycarboxylic acid salt content of the aqueous solution is usually in the range of about 0.1 to 60, 1 to 30 or 5 to 15 wt .-%, based on the total weight of the original (ie without acid (catalyst) and without alcohol). In the case of using a fermentation broth as a template, the Polycarbonsäuresalzgehalt z. B. at about 10 to 40 or 15 to 30 wt .-% and the Wasserateil at about 40 to 70 or 50 to 60 wt .-%, with conventional residues from the fermentation in a proportion of about 5 to 20 wt. % may be included in addition.

The salt of a carboxylic acid used in the invention is preferably selected from in each case straight-chain or branched, aliphatic, or cycloaliphatic, saturated or unsaturated, C ₂ - C ₂ o-, such as C ₃ - C ₀ - polycarboxylic acids, particularly polycarboxylic acids having 4, 5 or 6 carbon atoms. Polycarboxylic acids are in particular selected from carboxylic acids having two or more, such as, for example, 2, 3 or 4 carboxyl groups, in particular dicarboxylic acids, preferably saturated dicarboxylic acids, and mixtures thereof. In addition, suitable polycarboxylic acids may be substituted by further, for example 1 to 5 functional groups, for example hydroxy groups or mercapto groups.

The polycarboxylic acid is partially or completely neutralized with suitable bases. The base used according to the invention is, in particular, ammonia, an ammonium salt, ammonium hydroxide or an alkali metal or alkaline earth metal diallyl salt, such as sodium hydroxide, lithium hydroxide, potassium hydroxide, barium hydroxide, calcium hydroxide and magnesium hydroxide.

Typical salts of polycarboxylic acids are ammonium salts or alkali metal salts, e.g. Sodium or potassium salts, or mixed forms thereof.

Nonlimiting examples of suitable polycarboxylic acids include:

Dicarboxylic acids, such as oxalic acid (ethanedioic acid), malonic acid (propanedioic acid), succinic acid (butanedioic acid), glutaric acid (pentanedioic acid), adipic acid (hexanedioic acid), pimelic acid (heptanedioic acid), suberic acid (octanedioic acid), azelaic acid (nonanedioic acid), sebacic acid (decanedioic acid), dodecanedioic acid, Tetradecanedioic acid and hexadecanedioic acid; Maleic acid, itaconic acid, fumaric acid; Ci-Cβ-alkyl-substituted derivatives thereof, such as 2- or 3-methylglutaric acid; and their hydroxy-substituted derivatives, e.g. Malic acid or 2-hydroxyglutaric acid; or mixtures thereof.

Tricarboxylic acids, such as citric acid; Agaric acid, propane-1,2,3-tricarboxylic acid (tricarballylic acid), aconitic acid or mixtures thereof Higher polycarboxylic acids, obtainable, for example, by polymerization of monomers selected from acrylic acid and polymerizable derivatives thereof.

According to the invention, the terms "alkanol" and "alcohol" are used interchangeably. In particular, at least one alkanol in concentrated or diluted form, or as pure substance, such as anhydrous, is used for the esterification. The alcohol is selected from straight or branched CRCI ₀ -, -C ₈ -, C - C ₆ -, -C ₄ or C ₃ -C ₆ - monoalkanols, in particular straight-chain or branched Ci - C ₃ - mono-alkanols and mixtures thereof. For example, the alcohol, methanol, ethanol, n- or i-propanol, 1-, 2- or tert-butanol, or n-pentanol, n-hexanol, n-heptanol, n-octanol, 2-ethylhexanol, n-nonanol , n-decanol, or an isomeric form of these n-alkanols.

According to a preferred embodiment, the alkanol used is methanol and the acid used is succinic acid and the esterification product is succinic acid dimethyl ester.

In principle, it is not necessary for the starting materials used (carboxylic acid salt, alkanol) to be completely dissolved in the reaction medium, in particular in its aqueous phase. A partial solution is conceivable in principle, e.g. only about 1 to 99% e.g. 10 to 90% of the reactant used in each case are dissolved, and undissolved constituents can be converted into solution during the course of the reaction and then reacted.

The method according to the invention can be carried out in different modes of operation, such as in batch mode, semi-batch mode or continuously.

In particular, in a continuous mode of operation, it is advantageous to have reusable by-products of the reaction, e.g. recover the alkanol or organic solvent (such as toluene) and recycle it to the process at the appropriate place.

In the process according to the invention, the reaction is carried out in particular in the presence of a homogeneous or heterogeneous esterification catalyst. The heterogeneous catalyst is in particular an acidic ion exchanger catalyst and may optionally be fixed on or in reactor internals.

The homogeneous catalyst used is in particular one which is added to the aqueous salt solution of the carboxylic acid. In particular, the homogeneous catalyst used is a Acid. The acid used is a proton source selected from sulfuric acid, hydrochloric acid, phosphoric acid, organic carboxylic acids. In a preferred embodiment sulfuric acid is used as the acid.

In addition to the surprisingly selective extraction of the diester which forms, this has the further advantage over the prior art that the problem of equilibrium and thus limitation of the conversion otherwise occurring when using aqueous solutions of higher alkanols with carboxylic acid salts does not exist and enables a more uniform process procedure according to the invention becomes.

Surprisingly, it could be shown that the presence of the water-immiscible, organic solvent (such as toluene) during esterification in aqueous medium has significant advantages over a subsequent extraction (after completion of the reaction), which in particular in a significantly higher yield of Wertpro - express the product.

Surprisingly, it has also been shown that a significant decolorization is achieved by distillation of the polyester (such as succinic acid dimethyl ester).

Thus, in accordance with the present invention, carboxylic acid polyesters can be prepared in quantitative or near quantitative yield (such as greater than 70%, or greater than 80, 85, or 95%), with the resulting reaction mixtures having very good purity upon distillation. Furthermore, it can be observed that after completion of the reaction and the extraction, the polycarboxylic acid content in the aqueous phase is less than about 10 mol%, such as e.g. is less than about 5, 2, 1 or 0.1 mol% of the amount used.

Overall, the skilled worker can achieve a desired high, preferably quantitative ester yield by optimizing the reaction conditions, such as residence time, reactor temperature, optionally pressure, and / or molar ratio of the starting materials and catalysts.

The subsequent distillation of the polyester further increases the purity of the polyester.

The alkanol used in the esterification reaction and the organic phase (optionally together with small amounts of alkanol) can be distilled off via the top of the column, with an alkanol / water mixture or azeotrope Qe after alkanol used) and Alkanol / organic phase mixture or azeotrope Ge after used organic phase) distilled off, condensed, from the condensate, the alkanol or the organic phase gains and returns to the reaction, or an alkanol / water hetero-azeotrope distilled off, condensed, from the Condensate separates the organic alkanol phase (such as by phase separation or by distillation), or an alkanol / water / organic phase hetero-azeotropically distilled off, condensed, separated from the condensate, the organic phase (such as by phase separation or by distillation) and in the implementation leads back. Azeotropic mixtures can be formed especially when using ethanol, propanol and butanol; Hetreo azeotropes using butanol, pentanol and higher alcohols.

If more volatile components than the alcohol-containing azeotrope or alcohol-water mixture to be separated occur during distillation, these more volatile components can be removed overhead.

After isolation of the polyester this can be hydrolyzed back to the acid, which then continues to reach the surprisingly high purity.

The invention thus also provides a process for the preparation of a polycarboxylic acid which comprises first preparing a polycarboxylic acid ester using an esterification process as defined above and hydrolyzing the esters in the presence of water.

This reaction is carried out in the presence of an esterification catalyst which is a homogeneous or heterogeneous catalyst which may be as defined above.

In a particular embodiment of the process according to the invention, the desired product, in particular succinic acid, is isolated by crystallization after hydrolysis.

2. Further embodiments of the invention

Unless otherwise specified herein, the following general definitions apply:

"Alkyl" stands for straight-chain or branched alkyl radicals having 1 to 12 C atoms, in particular for the C 1 -C ₅ radicals methyl, ethyl, i- or n-propyl, n-, i-, sec- or tert. butyl, n- or i-pentyl; also C ₆ - C ₂ radicals n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, as well as one or multiply branched analogues thereof.

The above definitions apply correspondingly to C 1 -C ₄ -alkyl radicals, C 1 -C -alkyl, C 1 -C -alkyl radicals reste Ci - Ci ₀ alkyl or C ₃ - C ₆ alkyl radicals.

"Monoalkanols" are derived from the above alkyl groups by introducing a hydroxyl radical, respectively.

a) Fermentative production of carboxylic acid salts

The fermentative preparation of aqueous salt solutions of polycarboxylic acids is known per se from the prior art. For example, US Pat. No. 5,869,301 describes the fermentative production of carboxylic acids, in particular succinate, from glucose using various microorganisms, in particular bacteria of the genus Escherichia.

Examples of suitable natural or recombinant, pro- or eukaryotic microorganisms are those which are suitable for the fermentative production of the desired polycarboxylic acid under aerobic or anaerobic conditions. In particular, bacteria must be mentioned, such as those of the genus Escherichia, Bacteroides , Anaerobiospirillum, Actinobacillus and Mannheimia and fungi of the genus Rhizopus and Aspergillus. In particular, for example, bacteria such as E. coli, anaerobiopirillum succini-producing, Actinobacillus succinogenes, Mannheimia succiniproducens or other bacteria or fungi containing the desired carboxylic acid, e.g. Succinic acid, produce, name.

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 see, for example the embodiments in suitable technical literature, such. Rehm et al, Biotechnology, Vol. 3 Bioprocessing, 2nd ed., (Verlag Chemie, Weinheim).

For this purpose, a sterile culture medium is prepared, which contains the substrate and other necessary for the growth of the microorganism and product formation additives such as carbon and / or nitrogen sources, trace elements and the like, and inoculated with a suitable amount of a fresh preculture of the microorganism. The cultivation takes place continuously or discontinuously in a suitable fermenter with the polycarboxylic acid (or salts thereof) accumulating in the medium. During fermentation, the pH of the fermentation medium is adjusted by adding base-containing solutions such as ammonium, sodium, potassium, calcium or magnesium hydroxide or carbonate to prevent inhibition of the culture. In principle, however, the introduction of ammonia is conceivable. After the fermentation has ended, the fermentation broth containing the salt of the polycarboxylic acid, preferably dissolved, are fed either directly to the esterification reaction according to the invention. Preferably, however, first biomass, for example, separated by centrifugation or filtration. Optionally, after washing the separated biomass and combining the wash liquor with the salt solution, the concentration, if too low, for example, by distillative separation of water, can be further increased to form a concentrated aqueous carboxylic acid salt-containing phase has a percentage of salt of the polycarboxylic acid in the range of about 1 to 70, preferably 10 to 50 weight percent. This aqueous concentrate is then fed to the esterification reaction.

In one embodiment of the process according to the invention, the fermentation broth is prepared by anaerobic or aerobic fermentation or a combination of aerobic and anaerobic fermentation, preferably by the fermentation of carbon sources, such as CO ₂ , oils or alcohols, in particular glycerol, ethanol, methanol, or sorbitol, or sugars, such as C ₆ - or C ₅ sugars, in particular glucose, sorbose, arabino nose, xylose, maltose or sucrose, in pure form or as a molasses or mixtures of said substances or their precursors, such as. As starch, for example, together with enzymes, or other possible carbonaceous compositions such. As cellulose, for example in the form of waste paper, wood waste or components of starchy plants.

In one embodiment, in fermentation, a microorganism, such as E. coli, is transferred to anaerobic conditions after an aerobic growth phase to develop biomass. In this anaerobic phase, the synthesis of succinate takes place. Both cultivation steps can take place in particular in complex medium. In a further embodiment, in the fermentation, the cultivation of the microorganism, in particular E. coli, in the anaerobic phase with minimal medium. Another embodiment comprises recycling the cells several times and carrying out the anaerobic production phase on complex or minimal medium.

The fermentation can be carried out in stirred fermenters, bubble columns and loop reactors. A detailed overview of the possible embodiments, including stirrer shapes and geometrical designs, can be found in "Chmiel: Bioprocessing Technology: Introduction to Bioprocess Engineering, Volume 1." The process control typically involves the following, known to the person skilled in the art or, for example, in "Chmiel , Hammes and Bailey: Biochemical Engineering ", such as batch, fed-batch, repeated fed-batch or else continuous fermentation with and without recycling of the biomass. Depending on the production strain, fumigation with air, oxygen, carbon dioxide, or hydrogen, nitrogen or corresponding gas mixtures in order to achieve good yields.

Before the reaction in the fermentation broth in the process according to the invention, 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 depends on the biomass fraction in the fermenter broth and the properties of the biomass, as well as the interaction of the biomass with the desired product. The fermentation broth may in one embodiment be sterilized or pasteurized.

In a further embodiment, the fermentation broth is concentrated. This concentration or evaporation can be carried out batchwise or continuously as required. The pressure and temperature range should be chosen so that on the one hand no product damage occurs, on the other hand a minimized use of equipment and energy is necessary. In particular, the clever choice of pressure and temperature stages for multi-stage evaporation enables energy to be saved.

Apparatus can be used to stirred tank, falling film, thin film, Zwangsentspannungsumlauf-, and other evaporator types in natural or forced circulation.

Consequently, the term "fermentation broth" is understood to mean an aqueous solution based on a fermentative process which has not been worked up or worked up, for example, as described herein.

b) Reactive extraction of the ester

According to the invention, a "reactive extraction" is understood to be the simultaneous performance of a chemical reaction and an extraction. This simultaneous implementation of reaction and extraction is particularly advantageous in those reactions in which the starting materials are not completely converted into the desired products due to the position of the chemical equilibrium The simultaneous separation of the reaction products from the reaction space makes it possible to achieve better conversion in a single apparatus.

The apparatus implementation of the reactive extraction according to the invention is in various Embodiments possible. In principle, suitable for this purpose are all known types of reactors in which a simultaneous extraction is possible.

c) Suitable reactants, esterification catalysts and solvents

According to the invention, esterifiable polycarboxylic acids and alkanols and extractants which can be used according to the invention have already been described in more detail above.

The molar ratio of carboxylic acid or salts to alkanol in the esterification according to the invention is usually in the range from 1: 2 to 1:50, such as e.g. 1: 2 to 1:40 or 1: 2 to 1: 30.

The molar ratio of carboxylic acid or salts to organic phase solvent is usually in the range of 1: 1 to 1:40, e.g. 1: 1 to 1:25 or 1: 1 to 1:10.

Examples of suitable solid esterification catalysts are ion exchange resins available under the trade designations Amberlyst 15 or Amberlyst 16 (Rohm and Haas) or DPT1 (Davy Process Technology Limited).

Suitable liquid or dissolved esterification catalysts are sulfuric acid, p-toluenesulfonic acid or methanesulfonic acid.

The pH values of the aqueous reaction mixture are preferably in the range of about 3 to 0. *** "

d) esterification process

The esterification process according to the invention, which essentially comprises a reactive extraction, can be carried out in various embodiments using technical devices known per se. Two non-limiting, specific examples of methods according to the invention for the preparation of BSDME and extraction with toluene are explained in more detail below with reference to the accompanying figures.

Figure 1 shows a schematic representation of an example of an apparatus for carrying out the esterification according to the invention by stepwise reactive extraction (p = 1 bar, T = 70 ⁰ C) of succinic acid dimethyl ester (BSDME), wherein the addition of toluene takes place in countercurrent in the stirred reactor 203. The esterification takes place in the stirred reactors R200 to R203 the are connected to each other via the phase separation devices PT200 to 203. The reactants succinic acid (BS) (as ammonium salt in fermentation broth with initial concentration BS: ca.140 g / l), sulfuric acid and methanol are fed into the reactor R200. The toluene phase of PT203 separated from R203 is fed overhead into R202. The procedure is analogous to the toluene phases obtained from R202 and R201. The toluene phase obtained from PT200 was worked up by distillation in K200. Toluene is distilled off, crude BSDME remains as a dark oil and can be further separated by distillation. Methanol is distilled off from the aqueous phase obtained from the precipitator PT203. The aqueous residue containing salts, residual toluene and bioproducts from the fermentation broth is disposed of.

Figure 2 shows the flow diagram of an overall process according to the invention for the production of succinic acid (BS), starting from a fermentation of the resulting salt of succinic acid with methanol to dimethyl succinate (BSDME), its reactive extraction with toluene, the distillation of this intermediate and the hydrolysis of the Esters to the BS.

Further modifications of the above-described specific embodiments of devices and modes of operation which can be used according to the invention are conceivable in principle and can be realized by the skilled person without undue burden.

Suitable process parameter ranges for the esterification process of the present invention will be appreciated by those skilled in the art, depending on the design of the apparatus used, e.g. Type of column internals used, type and amount of reactants, type and amount of catalyst optionally used readily determinable. Thus, without being limited to and independently of each other, individual parameters can be set within the following parameter ranges:

Reactor temperature: 0 - 250 ⁰ C, in particular 40 - 150 ⁰ C, or 70 - 100 ⁰ C pressure: 0.1 to 6 bar, such as about 1 to 2 bar.

Dwell time: a few seconds (such as 1 to 60) to days (such as 1 to 5), especially a few minutes (such as 1 to 60) to a few hours (such as 1 to 15), more preferably a few minutes (such as 5 to 20) to 2 h

e) distillation variants

After the reactive extraction of the desired product, the alkanol (such as methanol) is recovered from the aqueous phase by distillation. The organi- zation used for extraction see solvent is also recovered by distillation from the product phase value.

Subsequently, the desired product is purified by distillation overhead.

For these distillations, e.g. a rectification column usable. A "rectification column" usually consists of an evaporator at the bottom, a condenser at the top and various internals in the column Depending on the type of internals used, a distinction is made between bottom, packed and packed columns. In the top, the lower-boiling components accumulate and can be separated there.To achieve separation in the column, a partial stream of the condensate is usually returned to the column.The heavier-boiling components accumulate in the bottom and can be removed there It is also possible, depending on the separation problem, to extract through a side draw components between the lightest and the heaviest boiling components.

In typical tray columns sieve, bell or valve trays are installed, over which the liquid flows. Through special slots or holes of the steam is passed, so that a bubble layer is formed. On each of these soils, a new evaporation equilibrium sets in.

Packed columns can be filled with differently shaped packings. Due to the associated surface enlargement of about 3-50 mm large packing heat and mass transfer are optimized and thus increases the separation capacity of the column. Typical examples of such substrates are the Raschig ring (a hollow cylinder), Pall ring, Hiflow ring, Intalox saddle, Berl saddle and hedgehog. The packing can be ordered, but also random (as a bed) are introduced into the column. Possible materials are glass, ceramics, metal and plastics.

Structured packings are a further development of the ordered packing. They have a regularly shaped structure. There are different versions of packages z. B. tissue or sheet metal packages. The material used can be metal, plastic, glass and ceramics. Packing columns have a very low liquid content compared to tray columns. This is often advantageous for rectification because it reduces the risk of thermal decomposition of the substances.

f) hydrolysis variants of the ester The product of value (polycarboxylic acid polyester) which has been further purified by reactive extraction and, if necessary, also by distillation can then be converted again to the free acid using generally known processes for the hydrolysis of the ester.

Experimental part

1. General information:

Analysis of acids / monoesters / diesters by HPLC: Device: Agilent Series 1100

Column: Zorbax Eclipse XDB-C18 1, 8μm 50 ^* 4.6mm from Agilent®

Eluent: -A: water with 0.1% by volume H ₃ PO ₄

B: acetonitrile with 0.1% by volume H ₃ PO ₄

Detector: UV detector λ = 204 nm, BW = 4 nm

Flow rate: 1 ml / min

Injection: 5 μL

Temperature: 30 ^° C

Running time: 8 min

Pressure: approx. 280 bar

2. Examples

Example 1: Preparation of succinic acid dimethyl ester (BSDME) by means of reactive extraction - reaction in the two-phase system

BS BSMME BSDME An aqueous fermentation broth (1200 g) (1300 ml) with a succinic acid content of 13% by weight (neutralized in the present case as sodium and / or ammonium salt) together with methanol (270 ml) (molar ratio BS: methanol ca 1: 5 (600 mL) and sulfuric acid (95% pure), toluene, 480 g) heated to 70 ⁰ C. After one hour, extraction was carried out and the aqueous / methanolic phase was again mixed with fresh toluene (500 ml) and the first organic phase was separated. After four hours, a total of four extractions were carried out. In the aqueous phase, only traces of succinic acid and succinic acid monomethyl ester (BSMME) were found.

Subsequently, the solvent of the organic phase was removed. In this way, 170 g of a colored oily residue containing BSDME was obtained.

This residue was then subjected to distillation under reduced pressure (50 mbar) and at 98-110 ⁰ C, the main part of the BSDME went overboard. In this way, 154 g of BSDME were obtained as a colorless oil. (Yield 80%, purity greater than 99%)

Example 2 Investigation of the Significance of the Presence of the Organic Phase During the Esterification of Succinic Acid Dimethyl Ester

An aqueous fermentation broth (750 g) dissolved with succinic acid as the diammonium salt (15% by weight) was treated with sulfuric acid (95% strength, 350 g) and methanol (190 ml) (molar ratio BS: methanol about 1: 5). Subsequently, this mixture was heated to 70 ⁰ C and stirred for one hour at this temperature. After this time, toluene (450 ml) was added to the batch and phase separation was performed.

The organic phase contained 9.9% by weight of succinic acid dimethyl ester. Compared with experiments in which the organic phase is already present during the reaction (see Example 1 above), the yield decreases by 10%.

Example 3: Hydrolysis of succinic acid dimethyl ester

Succinic acid dimethyl ester (142 g, prepared according to Example 1) was added dropwise to 3 N hydrochloric acid (1400 g) and the biphasic mixture was heated at 80 ° C. for two hours. The solvent was then removed and the succinic acid isolated as a solid. In this way, 106 g of product were obtained, corresponding to a yield of 100%. Example 4 Reactive Extraction of Succinic Diethyl Ester (BSDEE)

An aqueous fermentation broth 370 g with succinic acid dissolved as diammonium salt present (12 wt.%) Was treated with sulfuric acid (3.5 eq., 135 g, 95%), ethanol (110 ml) and toluene (150 ml) (BS : EtOH about 1: 5). Subsequently, this mixture was heated to 70 ⁰ C and after 15 minutes the first phase separation tried. However, a three-phase mixture was found. Subsequently, the uppermost phase was removed, added to the residue fresh toluene (75 ml_) and stirred at 70 ⁰ C for 15 minutes. After renewed phase separation, the extraction was repeated twice more, so that in total four extractions were carried out. While product (BSDEE) could be detected, the rate of reaction for this three-phase mixture is significantly slower. The analytically proven amount of BSDEE corresponds to a yield of about 60%.

Example 5: Experiments with various organic solvents for the optimization of the extraction of succinic acid methyl esters

Different solvents were tested under different conditions for their extraction behavior for BS, BSMME and BSDME to find out which conditions are suitable for the most selective extraction of BSDME.

The experimental conditions and test results are summarized in the following table.

Note: The column "HPLC" shows the weight% obtained for the given combination of succinic acid (derivative), solvent and pH. The reported yield indicates the proportion of succinic acid (derivative) present in the It should be noted that about 70% of methyl succinate is detected in the organic phase in methyl THF at a pH of 2. In toluene, on the other hand, less than 1% of succinic monomethyl ester is found in the organic phase. The ester is 80% in the organic phase and these values are highlighted in the table.

It is thus observed that by selecting the solvent and optionally additionally by adjusting the extraction conditions, a selective extraction of BSDME can be achieved.

Claims

claims

A process for producing a polyalkyl ester of a polycarboxylic acid, which comprises conducting a reactive extraction by contacting an aqueous solution comprising a salt of at least one polycarboxylic acid with an alkanol in the presence of an esterification catalyst in an at least two-phase aqueous-organic solvent system; at least one Polycarbonsäurepolyalkylester-containing organic extract phase removed from the reaction mixture.

2. The method of claim 1, wherein the at least two-phase, aqueous-organic system is present during the entire course of the esterification reaction or is formed only after the start of the esterification reaction.

3. The method according to any one of the preceding claims, wherein the at least zweiphha- sige, aqueous-organic system is formed by addition of a water-immiscible organic extractant.

The process of claim 3, wherein the extractant selectively removes polycarboxylic acid alkyl ester from the aqueous phase of the reaction mixture.

5. The method according to any one of claims 3 and 4, wherein the extractant used is a water-immiscible organic solvent which is selected from cyclic compounds selected from aromatic or non-aromatic, optionally mono- or polyunsaturated, C ₅ - Ci ₂ - hydrocarbons; non-cyclic compounds selected from saturated and mono - or polyunsaturated, branched or unbranched C ₅ - C ₂ - hydrocarbons.

6. A process according to any one of the preceding claims, wherein the volume ratio of aqueous phase to organic extract phase is in the range of about 10: 1 to 1:10.

7. The method according to any one of the preceding claims, wherein the extraction is repeated at least once by adding the water-immiscible organic extractant to the remaining reaction mixture again and Polycarbonsäurepolyal- kylester-containing organic extract phase removed from the reaction mixture.

8. The method according to any one of the preceding claims, wherein a carboxylic acid is used which is selected from in each case saturated or unsaturated C ₂ - C ₂ 0 -polycarboxylic acids.

9. The method according to any one of the preceding claims, wherein one uses an alkanol which is selected from straight-chain or branched Ci - Ce- monoalkanols.

10. The method according to any one of the preceding claims, wherein the reaction is carried out in the presence of a homogeneous or a heterogeneous esterification catalyst.

11. The method of claim 10, wherein using a homogeneous catalyst.

12. The method of claim 10 or 11, wherein the employed homogeneous catalyst is an acid.

13. The method according to any one of the preceding claims, wherein after completion of the reaction and extraction of the polycarboxylic acid content in the aqueous phase is less than about 10 mol% of the amount used.

14. The method according to any one of the preceding claims, wherein distilled off after depletion of the polycarboxylic acid residues of the alkanol used over the top of the column from the remaining reaction mixture.

15. The method according to any one of the preceding claims, wherein the polycarboxylic acid salt used is prepared chemically, enzymatically or microbiologically.

16. The method according to any one of the preceding claims, wherein the alkanol used is methanol.

17. The method according to any one of the preceding claims, wherein the polycarboxylic acid is succinic acid.

18. The process according to claim 17, wherein di-methyl-succinate is obtained.

19. The method according to any one of the preceding claims, wherein the obtained organic extract phases are worked up by first the organic solvent removed by distillation and then the contained polycarboxylic acid removed by distillation.

20. A process for the preparation of a polycarboxylic acid, which comprises first preparing a polycarboxylic acid ester using a process according to any one of the preceding claims and hydrolyzing the ester to form the desired product.

21. The method according to claim 20, wherein the product of value is isolated by crystallization after hydrolysis.