Method for obtaining organic acid from aqueous mother liquor

Abstract

The present invention relates to a method for obtaining aminobenzoic acid or an aliphatic saturated C 4~6 dicarboxylic acid from an aqueous solution, the method comprising: A) producing an organic acid, wherein a) the organic acid is crystallized from an aqueous medium, and subsequently, the precipitated portion of the organic acid is separated via solid-liquid separation, leaving an aqueous solution of the first organic acid; B) treating the aqueous solution of the organic acid with a metal salt of Mn 2+ , Fe 2+ and / or Cu 2+ to precipitate a metal compound of the organic acid, and subsequently separating the precipitated metal compound via solid-liquid separation; C) subjecting the separated metal compound to a base treatment to precipitate a metal hydroxide, and separating the precipitated metal hydroxide via solid-liquid separation, leaving a basic aqueous solution containing an anion of the organic acid; and D) crystallizing the organic acid by adding an inorganic acid to the basic aqueous solution obtained in C).

Description

Technical Field

[0001] The invention on which the present application is based was financially supported by the Federal Ministry of Food and Agriculture of Germany as part of the project "Biobased Production of Intermediates for Polyurethanes - Phase II (Bio4PURPro)" (funding code 22019918).

[0002] The present invention relates to a method for obtaining an organic acid from an aqueous solution of the organic acid, wherein the organic acid is selected from optionally methyl-substituted aminobenzoic acid or aliphatic saturated C4-C6 dicarboxylic acid, and the method comprises: A) preparation of the organic acid by a biological process or a chemical reaction, wherein α) the organic acid is crystallized from an aqueous medium during or after the preparation, and subsequently, 1) the fraction of the organic acid precipitated in the crystallization is removed by solid-liquid separation, leaving a first aqueous solution of the organic acid, and optionally, 2) the fraction of the organic acid dissolved in the first aqueous solution of the organic acid is depleted by extracting the organic acid with an organic extractant or adsorbing the organic acid onto an adsorbent, and subsequently, the organic extractant or adsorbent is removed to obtain a second aqueous solution of the organic acid; and B) treating the first aqueous solution of the organic acid or the second aqueous solution of the organic acid with a metal salt containing metal ions Mn 2+ , Fe 2+ and / or Cu 2+ to precipitate a metal compound of the organic acid, and subsequently removing the precipitated metal compound of the organic acid by solid-liquid separation; C) treating the removed metal compound of the organic acid with an aqueous base solution to precipitate a metal hydroxide, and removing the precipitated metal hydroxide by solid-liquid separation, leaving a basic aqueous solution containing an anion of the organic acid; and D) crystallizing the organic acid from the basic aqueous solution containing the anion of the organic acid obtained in C) by adding an inorganic acid.

Background Art

[0003] The repetition feature of the preparation of the organic acid is also the crystallization step from an aqueous medium for the isolation and / or purification of the organic acid, and in some cases, the crystallization step from a solution containing the anion of the organic acid by lowering the pH (referred to as reactive crystallization). When the crystallized organic acid is removed, an aqueous solution of the organic acid (= mother liquor from crystallization) remains, which still contains a residual content of the organic acid corresponding to the solubility equilibrium and may in some cases be in the range of several grams per liter.

[0004] This example is the preparation of anthranilic acid. Anthranilic acid is used, for example, in the manufacture of dyes, odorants or pharmaceuticals. The preparation of heterocycles from anthranilic acid and its derivatives is the subject of the paper Synthesis of Heterocycles from Anthranilic acid and its Derivatives by Per Wiklund (Non-Patent Document 1). In Separation and Determination of Iron(II) and Iron(III) with Anthranilic Acid Using Solvent Extraction and Spectrophotometry published in Non-Patent Document 2, Donald L. Dinsel and Thomas R. Sweet describe the use of anthranilic acid as an extractant for iron salts. The reduction of iron(III) by anthranilic acid has been taken up by Alexander A. Kamnev and Ernoe Kuzmann in Moessbauer spectroscopic evidence for the reduction of iron(III) by anthranilic acid in aqueous solution published in Non-Patent Document 3. The redox chemistry and iron complex formation of anthranilic acid and 3-hydroxyanthranilic acid are the subject of the academic paper Iron chelation and redox chemistry of anthranilic acid and 3-hydroxyanthranilic acid: A comparison of two structurally related kynurenine pathway metabolites to obtain improved insights into their potential role in neurological disease development by V. Chobot, F. Hadacek, W. Weckwerth and L. Kubicova published in Non-Patent Document 4.

[0005] A further example of the use of anthranilic acid is its use in the production of aniline by decarboxylation (as described, for example, in Patent Document 1). Aniline is particularly important as an intermediate in the production of isocyanates. Anthranilic acid can be obtained, for example, by fermentation (see, for example, Patent Document 1 already mentioned) or chemically (for example, by Hofmann rearrangement of phthalimide, see, for example, Patent Document 2). Regardless of the exact production method, the above type of crystallization step is regularly carried out. As an example, the isolation of anthranilic acid from a fermentation broth containing anions of anthranilic acid by reactive crystallization can be mentioned (see Patent Document 1 again). Anthranilic acid is an example of aminobenzoic acid. A more important representative example of this group of compounds is anthranilic acid derivatives in which the hydrogen atoms of the benzene ring are substituted by methyl groups. The complex-forming properties of aminobenzoic acids having substitutions on the benzene ring are taken up in Non-Patent Document 5, in the paper Metal Ion Complexes of Aromatic Amino Acids - I. Ring Substituted Amino Benzoic Acids by J. S. Decker and H. Frye.

[0006] A further example is adipic acid. Adipic acid is an intermediate in the production of nylon. Adipic acid is also used as a precursor in the synthesis of polyester polyols for polyurethane products. Adipic acid can be obtained by fermentation (see, for example, Non-Patent Documents 6 and 7) or chemically (for example, by hydrogenation of muconic acid, see, for example, Patent Document 3, or by oxidation of cyclohexane, see, for example, Non-Patent Document 8). Here too, the above type of crystallization step regularly occurs. As an example, the purification of the reaction product from the hydrogenation of muconic acid by crystallization can be mentioned (see Patent Document 3). Adipic acid is an example of an aliphatic saturated dicarboxylic acid. A more important representative example of this group of compounds is succinic acid.

[0007] Therefore, in order to avoid yield loss and minimize wastewater pollution, it is important to reduce the residual content of organic acids in the mother liquor in a suitable manner.

[0008] Patent Document 4 describes a method for recovering adipic acid from an aqueous nitric acid-containing mother liquor obtained in the industrial production of adipic acid by selective crystallization of dissolved adipic acid. The mother liquor is mixed with an aqueous adipic acid solution having an adipic acid content of 0.5% by weight to 6% by weight in an amount such that the nitric acid content of the mixture decreases to 35% by weight to 50% by weight within a temperature range of 30°C to 60°C. Next, the mixture is cooled by at least 5°C over a period of 0.5 hours to 5 hours, where the crystallized adipic acid is isolated by filtration, and the resulting filtrate is sent for post-treatment with distilled glutaric acid.

[0009] Patent Document 5 describes a method for producing succinic acid and succinic acid esters from succinates in a fermentation broth. In the first step, succinic acid is produced by biological fermentation using a renewable carbon resource. The succinate undergoes a double replacement reaction with a strong acid in the fermentation process, and succinic acid is released. Succinic acid is obtained by fractional crystallization integrated with SMB (simulated moving bed type) chromatography for producing succinic acid and succinic acid esters.

[0010] Patent Document 1 of the international application, which has already been mentioned several times, discloses a preferred embodiment in this regard. The mother liquor obtained by crystallization is post-treated to obtain further aminobenzoic acid. This is achieved by a sequence consisting of an adsorption step and a desorption step. The resulting aminobenzoic acid-enriched desorbent is reused in the crystallization procedure. In this way, the yield loss is reduced. Adsorption is carried out with zeolite or activated carbon, and desorption is carried out with water having a pH in the range of 5 to 10 or, alternatively, with an organic solvent, particularly 1-dodecanol. A modification of such post-treatment by the sequence of the adsorption step and the desorption step is described in Patent Document 6 of the international application. The method disclosed therein is more specifically characterized in that desorption is carried out in an acidic environment (pH -0.8 to 3.0).

[0011] Similarly, Patent Document 2 of the international patent application already mentioned above describes a method for recovering anthranilic acid from the mother liquor by crystallization for the isolation of anthranilic acid obtained by Hofmann rearrangement. The sodium carbonate-containing product of Hofmann rearrangement is adjusted to a pH of 4.2 with sulfuric acid (a), and the precipitated anthranilic acid is filtered off (b). The remaining mother liquor is extracted with an organic solvent at a pH of 4.2, and the preferred organic solvents disclosed are acetate esters (especially ethyl acetate or butyl acetate), ketones (especially 2-butanone), and aromatic hydrocarbons (especially toluene). The organic extract obtained after phase separation (c) is then re-extracted with a sodium hydroxide solution (d), and anthranilic acid is transferred as the anthranilate anion to the aqueous phase obtained after phase separation (e). This aqueous anthranilic acid-enriched phase from the re-extraction is mixed with the product of Hofmann rearrangement and sent together to crystallization. The aqueous anthranilic acid-deficient phase obtained by extraction is adjusted to a pH of 1.5 with sulfuric acid, an organic solvent is added (f), and the mixture is separated into an aqueous phase and an organic phase (g). In this way, the organic impurities migrate to the organic phase. This organic phase is mixed with the organic phase from the re-extraction and distilled. The distillate can be reused in this process as a solvent. The distillation residue is incinerated. The aqueous phase from (g) is sent to wastewater after purification by the Fenton reaction. A particularly disadvantageous point of this method is the relatively high water solubility of the acetate esters and ketones. The acetate esters and ketones dissolve anthranilic acid efficiently, but due to their relatively high water solubility, they migrate to the aqueous phase in a non-negligible proportion. This firstly results in a yield loss and secondly increases the complexity of wastewater purification. Toluene is also disclosed as a suitable solvent in Patent Document 2 and has no described disadvantages, but its efficiency of dissolving anthranilic acid is quite low, which makes it difficult to develop an industrially feasible method using toluene as an extractant.

[0012] Patent Document 7 describes a method for removing anthranilic acid from wastewater produced in the manufacture of methyl anthranilate. In the described method, the wastewater produced in the manufacture of methyl anthranilate is mixed with acidic wastewater (especially sulfuric acid containing copper chloride) until a pH of 3.5 to 4.5 is established, and copper anthranilate is precipitated. The precipitated copper anthranilate is added to a stirring tank together with calcium oxide and mixed with an alkaline solution (pH 11 to 13). The mixture is heated to 90°C to 110°C and boiled for 30 minutes to 150 minutes. After filtration, the filtrate containing sodium anthranilate is decolorized and adjusted to a pH of 3.5 to 4.0 with hydrochloric acid. The precipitated anthranilic acid is washed and dried.

Prior Art Documents

Patent Documents

[0013]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Patent Document 5

Patent Document 6

Patent Document 7

Non-Patent Documents

[0014]

Non-Patent Document 1

Non-Patent Document 2

Non-Patent Document 3

[0015] None of the described prior art methods are without drawbacks, and therefore, further improvements were needed in the field of the recovery of organic acids from aqueous solutions (mother liquors) of organic acids. In particular, a desirable method would, firstly, be able to selectively and substantially completely remove the organic acid from the aqueous mother liquor without transferring other components, such as organic solvents, into the aqueous phase. Secondly, a desirable method would be able to return the removed organic acid to the aqueous phase in high concentration and high yield.

Means for Solving the Problems

[0016] In view of this requirement, the present invention provides a method for obtaining an organic acid from an aqueous solution of an organic acid, wherein the organic acid is (i) of the formula:

Chemical formula

Chemical formula

[0017] Quite surprisingly, by combining treatment with a specific type of metal salt (step B)) and base treatment (step C)), it is possible to provide an aqueous solution of a much higher concentration of an organic acid (anionic type) than the aqueous solution of the organic acid derived from A)α). As a result, it has been found that reactive crystallization (step D)) can be sent for further isolation of the organic acid.

[0018] All pH values in the context of the present invention relate to the temperature at which the corresponding step (e.g., step (D)) is carried out and can be easily measured with a glass electrode.

[0019] The biological method in the context of the present invention is the fermentation or enzymatic conversion of organic substances.

[0020] Thus, in the context of the present invention, the conversion of organic substances is called chemical (chemical conversion or chemical method) when it proceeds without using a fermentation or enzymatic process (i.e., purely thermally or using a non-biological catalyst).

Brief Description of the Drawings

[0021]

Figure 1

Figure 2

Modes for Carrying Out the Invention

[0022] First, an overview of various possible embodiments of the present invention is shown below.

[0023] In a first embodiment of the present invention that can be combined with all other embodiments, the base treatment in C) includes n steps that are carried out continuously, where n is a natural number in the range of 2 to 10, preferably 3 to 9, more preferably 4 to 8, in each of the n steps, a part of the metal compound of the removed organic acid is treated with an aqueous base solution to precipitate a metal hydroxide, and following each step, the precipitated metal hydroxide is removed by solid-liquid separation, leaving an aqueous basic solution containing an anion of the organic acid, and the aqueous base solutions in the second to nth steps each contain (optionally consisting of, i.e., containing no further optional components) the aqueous basic solution containing the anion of the organic acid obtained in the respective previous step, the crystallization of the organic acid in D) is carried out with the aqueous basic solution containing the anion of the organic acid obtained in the nth step of C).

[0024] In a second embodiment of the invention, which can be combined with all other embodiments when crystallization of the organic acid in D) and A)α) is not separately envisaged, crystallization of the organic acid in D) involves recycling to A)α) an aqueous basic solution containing the anion of the organic acid obtained in C) (i.e., in the case of its n-stage base treatment, in the n-th step of C)).

[0025] In a third embodiment of the invention, which can be combined with all other embodiments when crystallization of the organic acid in D) and A)α) is not separately envisaged, crystallization of the organic acid in D) is carried out separately from A)α).

[0026] In a fourth embodiment of the invention, which can be combined with all other embodiments, the metal hydroxide precipitated in C) is recycled to step B) and used as a constituent of the metal salt.

[0027] In a fifth embodiment of the invention, which can be combined with all other embodiments when not related only to the aliphatic saturated dicarboxylic acid of formula (II), the organic acid is an aminobenzoic acid of formula (I), in particular 2-aminobenzoic acid (anthranilic acid) or 2-amino-5-methylbenzoic acid, preferably 2-aminobenzoic acid.

[0028] In a sixth embodiment of the invention, which is a specific configuration of the fifth embodiment, a pH in the range of 3.0 to 4.7, preferably 3.2 to 3.7, more preferably 3.4 to 3.6, is established in A)α) by the addition of an inorganic acid, in particular hydrochloric acid, sulfuric acid, nitric acid or phosphoric acid, and the pH within the same range is maintained in B) (if the pH rises or falls too much as a result of the addition of the metal salt, an acid or base is optionally added).

[0029] In a seventh embodiment of the invention, which is a specific configuration of the fifth and sixth embodiments, step A) comprises a biological method, i.e., fermentation of a raw material containing a fermentable carbon-containing compound and a nitrogen-containing compound in the presence of microorganisms.

[0030] In the eighth embodiment of the present invention, which is a specific configuration of the seventh embodiment, (I)A)α) is carried out by performing fermentation at a pH in the range of 3.0 to 4.7, preferably 3.2 to 3.7, more preferably 3.4 to 3.6, such that the aminobenzoic acid of formula (I) crystallizes early in the fermentation. Or, (II) Fermentation is carried out at a pH in the range of greater than 4.7 to 11 (especially 6.0 to 11), preferably 4.8 to 9.0 (especially 6.0 to 9.0), more preferably 5.0 to 8.0 (especially 6.0 to 8.0), and A)α) is carried out by establishing a pH in the range of 3.0 to 4.7, preferably 3.2 to 3.7, more preferably 3.4 to 3.6 after fermentation.

[0031] In the ninth embodiment of the present invention, which is a specific configuration of the seventh and eighth embodiments, the microorganism is selected from Escherichia coli, Pseudomonas putida, Corynebacterium glutamicum, Ashbya gossypii, Pichia pastoris, Hansenula polymorpha, Kluyveromyces marxianus, Yarrowia lipolytica, Zygosaccharomyces bailii, or Saccharomyces cerevisiae.

[0032] In the tenth embodiment of the present invention, which is a specific configuration of the fifth and sixth embodiments, A) includes chemical conversion (i.e., a non-biological method).

[0033] In the 11th embodiment of the invention which is a specific configuration of the 10th embodiment, A) involves the conversion of an optionally methyl-substituted phthalimide or phthalamide in a basic medium with an alkali metal hypohalite (especially sodium hypochlorite), followed by the addition of an inorganic acid, especially hydrochloric acid, sulfuric acid, nitric acid or phosphoric acid, for the implementation of A)α).

[0034] In the 12th embodiment of the invention which can be combined with all other embodiments when not related only to the aminobenzoic acid of formula (I), the organic acid is an aliphatic saturated dicarboxylic acid of formula (II), especially hexane-1,6-dicarboxylic acid (adipic acid).

[0035] In the 13th embodiment of the invention which is a specific configuration of the 12th embodiment, a pH in the range of 0 to 4.0, preferably 1.8 to 3.0, more preferably 2.0 to 2.5 is established in A)α) by the addition of an inorganic acid, especially hydrochloric acid, sulfuric acid, nitric acid or phosphoric acid, and a pH in the range of greater than 4.0 to 7.0, preferably 4.7 to 5.8, more preferably 5.3 to 5.7 is established in B) by the addition of a base.

[0036] In the 14th embodiment of the invention which is a specific configuration of the 12th and 13th embodiments, A) includes a biological method.

[0037] In the 15th embodiment of the invention which is a specific configuration of the 14th embodiment, the biological method includes the fermentation of a raw material containing a fermentable carbon-containing compound in the presence of microorganisms.

[0038] In the 16th embodiment of the invention which is a specific configuration of the 15th embodiment, (I) A)α) is carried out by performing the fermentation at a pH in the range of 0 to 4.0, preferably 1.8 to 3.0, more preferably 2.0 to 2.5 so that the aliphatic saturated dicarboxylic acid of formula (II) crystallizes early in the fermentation, or, (II) Fermentation is carried out at a pH in the range of greater than 4.0 to 11 (especially 6.0 to 11), preferably 5.0 to 9.0 (especially 6.0 to 9.0), more preferably 5.0 to 8.0 (especially 6.0 to 8.0), and A)α) is carried out by establishing a pH in the range of 0 to 4.0, preferably 1.8 to 3.0, more preferably 2.0 to 2.5 after fermentation.

[0039] In the 17th embodiment of the present invention, which is a specific configuration of the 15th and 16th embodiments, the microorganism is selected from Escherichia coli, Pseudomonas putida, Corynebacterium glutamicum, Bacillus coagulans, Ashbya gossypii, Pichia pastoris, Hansenula polymorpha, Kluyveromyces marxianus, Yarrowia lipolytica, Zygosaccharomyces bailii, or Saccharomyces cerevisiae.

[0040] In the 18th embodiment of the present invention, which is a specific configuration of the 12th and 13th embodiments, A) includes chemical conversion (i.e., a non-biological method).

[0041] In particular, in the 19th embodiment of the present invention, which is a specific configuration of the 18th embodiment, when n = 2 (i.e., the organic acid is especially adipic acid), A) includes the hydrogenation of an aliphatic unsaturated dicarboxylic acid corresponding to the aliphatic saturated dicarboxylic acid of formula (II) (especially muconic acid, etc.) (A)α) is especially carried out for the purification of the product obtained in the hydrogenation).

[0042] In the 20th embodiment of the present invention, which is a more specific configuration of the 18th embodiment, the aliphatic saturated dicarboxylic acid of formula (II) is hexane-1,6-dicarboxylic acid (adipic acid), and A) includes oxidizing cyclohexane with oxygen or an oxygen-containing gas mixture (especially air) to obtain cyclohexanol and cyclohexanone, and then oxidizing them with nitric acid.

[0043] In the 21st embodiment of the present invention, which is a specific configuration of the 14th and 18th embodiments, A) involves the (enzymatic or chemical) cleavage of polyester.

[0044] In particular, as far as obtaining the aliphatic saturated dicarboxylic acid of formula (II) (preferably hexane-1,6-dicarboxylic acid, adipic acid) is concerned, in the 22nd embodiment of the present invention, which can be combined with all other embodiments, the metal ion of the metal salt used in B) is Fe 2+ and / or Cu 2+ and particularly contains Fe 2+ and Cu 2+ and is selected from the group consisting of (in particular, when obtaining the aliphatic dicarboxylic acid of formula (II), Cu 2+ is preferred).

[0045] In the 23rd embodiment of the present invention, which can be combined with all other embodiments, a pH in the range of 9.0 to 14, preferably 10 to 14, more preferably 11 to 13, is established in C) (in the case of n-stage base treatment, in each of the n steps of the base treatment).

[0046] In the 24th embodiment of the present invention, which can be combined with all other embodiments, the metal ion is added in B) in a sub-stoichiometric amount based on the amount of the organic acid.

[0047] In the 25th embodiment of the present invention, which can be combined with all other embodiments, the metal salt contains sulfate, chloride and / or hydroxide.

[0048] In the 26th embodiment of the present invention, which can be combined with all other embodiments, the solid-liquid phase separation in A), B) and / or C) is carried out by filtration, centrifugation or sedimentation, and optionally assisted by prior aggregation.

[0049] In the 27th embodiment of the present invention, which can be combined with all other embodiments, step 2) is carried out in A) The organic extractant is selected from (i) alcohols, especially alkanols having 4 to 12 carbon atoms (especially 1-decanol and / or 1-dodecanol), preferably 8 to 12 carbon atoms, more preferably 9 to 11 carbon atoms, (ii) ketones (especially methyl isobutyl ketone and / or cyclohexanone), (iii) ethers (especially diethyl ether), (iv) esters (especially butyl acetate), (v) aromatic, optionally halogen-substituted hydrocarbons (especially benzene, toluene, monochlorobenzene and / or dichlorobenzene), or (vi) a mixture of two or more of the above-mentioned extractants. The adsorbent is selected from (i) activated carbon, (ii) polymer-based adsorbents, (iii) graphite, (iv) polar adsorbents such as silica gel, limestone or aluminum silicate, in particular, or (v) a mixture of two or more of the above-mentioned adsorbents.

[0050] In the 28th embodiment of the present invention, which can be combined with all other embodiments, the removal of the metal compound of the precipitated organic acid by solid-liquid separation in B) leaves an aqueous phase adjusted to a pH in the range of 8.0 to 14, preferably 10 to 13, by the addition of a base, precipitates a metal hydroxide, which is removed by further solid-liquid separation and is then used as a constituent of the metal salt in B).

[0051] In the 29th embodiment of the present invention, which is a specific configuration of the 28th embodiment, the bases used to establish the pH include alkali metal or alkaline earth metal hydroxides, alkali metal or alkaline earth metal carbonates, alkali metal or alkaline earth metal bicarbonates, in particular sodium hydroxide solution, potassium hydroxide solution or calcium hydroxide solution.

[0052] The embodiments and possible further configurations of the present invention briefly outlined above will be clarified in detail below. All of the above embodiments and the further configurations of the present invention below can be combined with each other as desired, unless the contrary is clearly apparent to those skilled in the art from the context or explicitly stated.

[0053] Preparation of organic acid The preparation of the organic acid, which is step (A) of the method of the present invention, naturally depends on the type of acid desired. During or after the preparation, crystallization step A)α) is carried out.

[0054] Aminobenzoic acid of formula (I) When the aim is to obtain aminobenzoic acid of formula (I) (2-aminobenzoic acid (= anthranilic acid) is preferred), in step A)α), it has been found useful to establish a pH in the range of 3.0 to 4.7, preferably 3.2 to 3.7, more preferably 3.4 to 3.6 by the addition of an inorganic acid, in particular hydrochloric acid, sulfuric acid, nitric acid or phosphoric acid. The exact manner of carrying out the crystallization in step A)α) depends, in turn, on the manner of carrying out step A) as a whole.

[0055] Biological method In one embodiment, step A) comprises a fermentation step. This is carried out by converting a fermentable carbon-containing compound and a nitrogen-containing compound into the desired aminobenzoic acid or its anion in the presence of a microorganism. Such fermentations have already been described, see the references cited below. Microorganisms suitable for the fermentative preparation of aminobenzoic acid of formula (I) include, in particular, Escherichia coli, Pseudomonas putida, Corynebacterium glutamicum, Ashbya gossypii, Pichia pastoris, Hansenula polymorpha, Kluyveromyces marxianus, Yarrowia lipolytica, Zygosaccharomyces bailii or Saccharomyces cerevisiae.

[0056] The fermentation in step A) is preferably carried out such that the pH of the resulting fermentation broth is in the range of 3.0 to 11, preferably 4.7 to 11 (for case (II), see below). If necessary, the pH can be controlled by the addition of aqueous or gaseous ammonia, aqueous potassium hydroxide or aqueous sodium hydroxide (when the pH value is too low), or by the addition of mineral acids, in particular hydrochloric acid, sulfuric acid, phosphoric acid or nitric acid (when the pH value is too high). The various pH ranges within the mentioned pH range of 3.0 to 11 can be particularly optimal for various microorganisms. The pH in the fermentation also affects step A)α). This is because depending on the specific pH within the range of 3.0 to 11, aminobenzoic acid is present in the fermentation broth as a well-water-soluble anion (H2NC6H3(R)COO - ), or as a relatively low-water-soluble electrically neutral form (H2NC6H3(R)COOH or H3N + C6H3(R)COO - ).

[0057] Particularly at pH values in the range of 4.7 or less, preferably 3.7 or less, more preferably 3.6 or less, aminobenzoic acid is mainly or completely in the electrically neutral form, and thus crystallizes spontaneously during fermentation, so that a separate crystallization step is not required and the crystallized aminobenzoic acid can be isolated directly from the fermentation broth (for case (I)). In the case of (I), for example, the described procedure is particularly preferred when it brings benefits in fermentation, such as reducing the toxicity to microorganisms in the fermentation broth as a result of the precipitation of aminobenzoic acid.

[0058] In the case of (I), the fermentation is preferably carried out at a pH in the range of 3.0 to 4.7, preferably 3.2 to 3.7, more preferably 3.4 to 3.6. Step A)α) then becomes part of the fermentation. In this case, it is preferable to use eukaryotes, particularly yeasts, as the microorganism. In this regard, reference is particularly made to International Publication No. WO 2017 / 102853, which is an international patent application. It is preferable to use yeast cells that can convert a fermentable carbon-containing compound into aminobenzoic acid in the presence of a suitable nitrogen source, and the aminobenzoic acid thus formed is not immediately consumed in the intracellular biochemical process. As a result, aminobenzoic acid accumulates in the cells and is finally transferred to the fermentation broth. Eukaryotes such as Ashbya gossypii, Pichia pastoris, Hansenula polymorpha, Kluyveromyces marxianus, Yarrowia lipolytica, Zygosaccharomyces bailii, and Saccharomyces cerevisiae are preferably cultured in an acidic medium and are thus suitable for the case of (I) described herein. Step A)α) in the case of (I) is part of the fermentation. After the fermentation is completed, the precipitated aminobenzoic acid is separated by (first) solid-liquid separation and obtained as a mixture with the microorganism. The procedure for separating the two may be, for example, selectively dissolving aminobenzoic acid at its maximum concentration (e.g., in an aqueous base solution, an aqueous acid solution, or an organic solvent), and then, if necessary (by another crystallization or concentration), separating it again from this solution. This procedure may also involve taking the first part of the solid mixture, particularly 50%, in a minimum amount of aqueous base solution (e.g., to obtain a supernatant solution pH of 7.0), taking the second part of the mixture solid, particularly 50%, in a minimum amount of aqueous acid solution (e.g., to obtain a supernatant solution pH of 1.0), separating the undissolved components, and then mixing the remaining solutions at a relatively high concentration so that an isoelectric point or a pH close thereto is established in the resulting mixture and aminobenzoic acid precipitates again. The remaining mother liquor in the (second) solid-liquid separation after the precipitated aminobenzoic acid is separated has a significantly smaller volume than the mother liquor obtained after the first solid-liquid separation and contains only a relatively small amount of aminobenzoic acid, so it can be disposed of or advantageously mixed with the mother liquor after the first solid-liquid separation.

[0059] The liquid phase obtained in the first solid-liquid separation in this embodiment, or the mixed liquid phase of the first solid-liquid separation and the second solid-liquid separation, is an "aqueous solution of an organic acid". The solid-liquid separation in the context of the present invention is preferably always (in any process step) carried out in the form of filtration, centrifugation or sedimentation, and optionally assisted by prior aggregation.

[0060] Particularly at a pH value above 4.7, preferably above 6.0, more preferably above 8.0, the aminobenzoic acid is mainly or completely in the anionic form, and thus, another crystallization step is carried out (in the case of preferred (II)). In the case of (II), the fermentation is preferably carried out at a pH in the range of above 4.7 to 11 (particularly 6.0 to 11), preferably 4.8 to 9.0 (particularly 6.0 to 9.0), more preferably 5.0 to 8.0 (particularly 6.0 to 8.0). In this case, it is preferred to use prokaryotes, particularly bacteria, as the microorganism. In this regard, in this specification, International Publication No. 2015 / 124686, which is a patent application, and Patent Document 1 are particularly referred to. These patent applications describe a fermentation process using bacteria (for example, see Patent Document 1, (i) line 8, page 15 to line 30, page 16, (ii) Example 1 (line 4, page 29 to line 26), (iii) Example 3 (particularly line 10, page 34 to line 18), (iv) Example 4 (particularly line 9, page 55 to line 31)), which is suitable for the case of (II) to obtain an anion of aminobenzoic acid as a direct fermentation process product. In particular, the bacteria used are such that they can convert a fermentable carbon-containing compound into aminobenzoic acid in the presence of a suitable nitrogen source, and the aminobenzoic acid thus formed is not immediately consumed in the intracellular biochemical process. As a result, the aminobenzoic acid is enriched in the cells and finally transferred to the fermentation broth. Microorganisms such as Corynebacterium glutamicum, Pseudomonas putida or Escherichia coli are preferably cultured at a "neutral to basic pH value" and are thus suitable for the case of (II) described in this specification. Since the aminobenzoic acid in this case is obtained in the form of an anion, in the downstream process of fermentation, by adding an inorganic acid, particularly hydrochloric acid, sulfuric acid, nitric acid or phosphoric acid, crystallization is carried out by establishing a pH in the range of 3.0 to 4.7, preferably 3.2 to 3.7, more preferably 3.4 to 3.6. In this case, step A) α) is thus a step following fermentation.

[0061] Chemical method In another embodiment, step A) involves a chemical conversion (i.e., a non-biological method). Particularly to be mentioned herein is the reaction of an optionally methyl-substituted phthalimide or phthalamide with an alkali metal hypohalite (especially sodium hypochlorite) in a basic medium. Such methods are known from the literature and are described, for example, in Patent Document 2. In this case, the desired aminobenzoic acid of formula (I) is obtained as an anion and crystallized by the addition of an inorganic acid, especially hydrochloric acid, sulfuric acid, nitric acid or phosphoric acid (= step A)α)).

[0062] When the crystallization step A)α) is carried out separately from the actual preparation, for example, in the case of the fermentation preparation of (II), or in the case of crystallization used for the purification of the raw material, as in the case of the reactor for the preparation of the organic acid, additional industrial equipment suitable for crystallization, known in the art as a crystallization device, is used. Suitable crystallization devices are, for example, stirred tanks or forced circulation crystallization devices, such as those of the "Oslo type". In the crystallization device, if necessary, the pH is adjusted to a suitable value, in the case of aminobenzoic acid of formula (I), in the range of 3.0 to 4.7, preferably 3.2 to 3.7, most preferably 3.4 to 3.6. This is preferably achieved by adding an acid selected from hydrochloric acid, sulfuric acid, nitric acid or phosphoric acid. By this adjustment of the pH, the main or complete conversion of the aminobenzoic acid anion (H2NC6H3(R)COO - ) to its electrically neutral form (H2NC6H3(R)COOH or H3N + C6H3(R)COO - ) and its crystallization are brought about. This type of crystallization is also called reactive crystallization. This crystallized aminobenzoic acid is isolated by solid-liquid separation, and an "aqueous solution of the organic acid" remains.

[0063] The aliphatic saturated dicarboxylic acid of formula (II) When the object is to obtain an aliphatic saturated dicarboxylic acid of formula (II) (hexane-1,6-dicarboxylic acid (= adipic acid) is preferred), in step A)α), it has been found useful to establish a pH in the range of 0 to 4.0, preferably 1.8 to 3.0, more preferably 2.0 to 2.5 by the addition of an inorganic acid, in particular hydrochloric acid, sulfuric acid, nitric acid or phosphoric acid. The exact method of carrying out the crystallization in step A)α) depends successively on the method of carrying out step A) as a whole. All possible configurations of the present invention described above in connection with the preparation of aminobenzoic acids of formula (I) which are not specific to these aminobenzoic acids are equally applicable in the case of the preparation of the aliphatic saturated dicarboxylic acids of formula (II) described below. This relates, for example, to the configuration of the crystallization apparatus.

[0064] Biological method In one embodiment, step A) comprises a biological method. In a first variant, this is carried out in particular by converting a fermentable carbon-containing compound and a nitrogen-containing compound into the desired aliphatic saturated dicarboxylic acid or its anion in the presence of a microorganism. Such fermentations have already been described, see in particular the non-patent documents 6 and 7 which have already been cited.

[0065] Microorganisms suitable for the fermentative preparation of the aliphatic saturated dicarboxylic acids of formula (II) include in particular Escherichia coli, Pseudomonas putida, Corynebacterium glutamicum, Bacillus coagulans, Ashbya gossypii, Pichia pastoris, Hansenula polymorpha, Kluyveromyces marxianus, Yarrowia lipolytica, Zygosaccharomyces bailii or Saccharomyces cerevisiae.

[0066] Similar to the above-described preparation of the aminobenzoic acid of formula (I), there is also pH dependence here. Depending on the pH at which the fermentation is carried out, the aliphatic saturated dicarboxylic acid either crystallizes already during the fermentation ((in the case of (I)) or the fermentation broth contains the aliphatic saturated dicarboxylic acid in the form of its anion, in which case reactive crystallization continues after the fermentation ((in the case of (II))). In the case of (I), the fermentation is preferably carried out at a pH in the range of 0 to 4.0, preferably 1.8 to 3.0, more preferably 2.0 to 2.5. The procedure for separating the microorganism and the organic acid may be such that, for example, the saturated aliphatic dicarboxylic acid is selectively dissolved at its maximum concentration (e.g., in an aqueous base solution or an organic solvent) and then, if necessary (by another crystallization or concentration), separated again from this solution. Step A)α) then becomes part of the fermentation. In the case of (II), the fermentation is preferably carried out at a pH in the range of above 4.0 to 11 (especially 6.0 to 11), preferably 5.0 to 9.0 (especially 6.0 to 9.0), more preferably 5.0 to 8.0 (especially 6.0 to 8.0). In this case, the aliphatic saturated dicarboxylic acid is obtained as an anion and is crystallized in the downstream process of the fermentation by establishing a pH in the range of 0 to 4.0, preferably 1.8 to 3.0, more preferably 2.0 to 2.5 by the addition of an inorganic acid, especially hydrochloric acid, sulfuric acid, nitric acid or phosphoric acid. In this case, step A)α) is therefore a step following the fermentation.

[0067] In a second variant of the preparation of organic acids using biological methods, enzymes are used for the cleavage of polyesters. The enzymatic cleavage of polyesters using cutinase for the release of adipic acid is described, for example, in the following academic paper: Perz, V., Bleymaier, K., Sinkel, C., Kueper, U., Bonnekessel, M., Ribitsch, D., & Guebitz, G. M. (2016), Substrate specificities of cutinases on aliphatic-aromatic polyesters and on their model substrates, in New biotechnology, 2016, 33(2), 295 - 304.

[0068] Chemical methods In another embodiment, step A) involves a chemical transformation (i.e., a non-biological method). Chemical methods for preparing certain types of dicarboxylic acids are known. By way of example, the hydrogenation of the corresponding aliphatic unsaturated dicarboxylic acid can be mentioned. In the case of the most strongly preferred adipic acid, the preparation can thus be carried out, for example, by the hydrogenation of muconic acid as described in Patent Document 3. In particular herein, step A)α) is carried out for the purification of the product obtained in the hydrogenation. Alternative means for the preparation of adipic acid have already been mentioned at the beginning and, as described several times in the literature, consist in oxidizing cyclohexane with oxygen or an oxygen gas mixture (in particular air) to cyclohexanol and cyclohexanone and subsequently oxidizing them with nitric acid (see Non-Patent Document 8 for a review).

[0069] In the case of a chemical transformation too, step A) may include the cleavage of a polyester by, for example, acid hydrolysis or alkaline hydrolysis. Furthermore, step A) may include, for example, the acid hydrolysis or alkaline hydrolysis of a polyamide based on hexamethylenediamine and adipic acid as described in U.S. Patent No. 3,223,731.

[0070] Any step of depleting the fraction of the inorganic acid dissolved in the aqueous solution of the first organic acid The aqueous solution of the first organic acid obtained by one of the methods described above can be fed directly to step B). However, equally, in another method, it is already possible to reduce this concentration of the organic acid in the aqueous solution of the first organic acid before carrying out step B). Suitable methods for this purpose are the methods of extraction and adsorption known in the art.

[0071] When using the extraction method, the aqueous solution of the first organic acid is extracted with an organic extractant, followed by liquid-liquid separation to obtain an aqueous phase (= aqueous solution of the second organic acid depleted of the organic acid) and an organic phase (= extractant containing the organic acid). Liquid-liquid separation in the context of the present invention is preferably always carried out by a separator, a decanter or a centrifuge (in any process step).

[0072] Suitable extractants are, for example, (i) alcohols, especially alkanols having 4 to 12 carbon atoms (especially 1-decanol and / or 1-dodecanol), preferably 8 to 12 carbon atoms, more preferably 9 to 11 carbon atoms, (ii) ketones (especially methyl isobutyl ketone and / or cyclohexanone), (iii) ethers (especially diethyl ether), (iv) esters (especially butyl acetate), (v) aromatics, optionally halogen-substituted hydrocarbons (especially benzene, toluene, monochlorobenzene and / or dichlorobenzene), and (vi) mixtures of two or more of the above-mentioned extractants.

[0073] Suitable apparatuses for carrying out the extraction are known in the art. Preferred examples include those called mixer-settlers or extraction columns, preferably having 3 to 10, more preferably 3 to 7, most preferably 4 to 6 theoretical plates. The mass-based phase ratio of the organic phase to the aqueous phase is preferably 0.20 to 1.0, more preferably 0.20 to 0.50, most preferably 0.35 to 0.50. After separation of the organic solvent phase and the aqueous phase, the aqueous solution of the organic acid is fed to step B). The extractant containing the organic acid is preferably sent to back-extraction, where the organic acid is converted to an anion by extraction with an aqueous base solution, and after phase separation, an aqueous phase containing the anion of the organic acid and an alcohol phase are obtained. Relatively polar impurities may occur in the preparation of the organic acid, and in particular these relatively polar impurities may move into the aqueous phase at least as a fraction in this step, so it is preferable to take measures for the discharge of such impurities. The extraction can be carried out at a temperature of 20°C to 90°C, preferably 25°C to 70°C, more preferably 30°C to 50°C, especially also at ambient temperature.

[0074] The aqueous base solution used for re-extraction is preferably an aqueous solution of an alkali metal or alkaline earth metal hydroxide (particularly a sodium hydroxide solution, a potassium hydroxide solution, or a calcium hydroxide solution), an aqueous solution of an alkali metal or alkaline earth metal hydrogen carbonate (particularly a sodium hydrogen carbonate solution or a potassium hydrogen carbonate solution), an aqueous solution of an alkali metal or alkaline earth metal carbonate (particularly a sodium carbonate solution or a potassium carbonate solution), or a mixture of two or more of the above compounds. Sodium hydroxide solution and potassium hydroxide solution are particularly preferred. Regardless of the base used, a molar ratio of hydroxide ions to organic acid groups of 1.0 to 5.0, preferably 1.0 to 2.0, more preferably 1.0 to 1.5, is preferably observed.

[0075] The apparatus suitable for this re-extraction is the same as that described above for extraction. The mass-based phase ratio of the organic phase to the aqueous phase is preferably 0.20 to 1.0, more preferably 0.20 to 0.50, and most preferably 0.20 to 0.40.

[0076] Instead of extraction, adsorption can also be used to deplete the organic acid in the first aqueous solution. For this purpose, the first aqueous solution is passed through a bed of adsorbent to which the organic acid adsorbs. Suitable adsorbents are typically non-polar adsorbents such as (i) activated carbon, (ii) graphite or (iii) adsorption polymers, but also typically (iv) polar adsorbents such as silica gel, limestone or aluminum silicate, and (v) mixtures of two or more of the above-mentioned adsorbents. Adsorption is preferably carried out by flowing the aqueous solution through the adsorbent until the adsorption characteristics of the adsorbent decrease and regeneration of the adsorbent by desorption of the organic acid is required. Desorption is preferably carried out with an aqueous solution having a pH in the range of 5 to 10 (e.g., pH adjustment with sodium hydroxide solution or hydrochloric acid), or alternatively with an organic solvent, especially 1-dodecanol. A variant of such a post-treatment by the sequence of the adsorption step and the desorption step is described in Patent Document 6 which is an international application. The method disclosed therein is more specifically characterized in that desorption is carried out in an acidic environment (pH -0.8 to 3.0). In this embodiment, the liquid phase leaving the adsorbent bed during the desorption process is an aqueous solution of the second organic acid and is fed to step B).

[0077] Suitable apparatuses for carrying out adsorption are known in the art. A suitable example is a column, and on a laboratory scale, in particular in the form of an adsorption bed, a suitable chromatography column filled with an adsorbent.

[0078] Metal salt treatment In step B) of the method of the present invention, the aqueous solution of the first organic acid or the aqueous solution of the second organic acid obtained in step A) contains metal ions of Mn 2+ , Fe 2+ and / or Cu 2+ and is treated with a metal salt selected from the group consisting of, in particular, Mn 2+ , Fe 2+ and Cu 2+ to precipitate a metal compound (a poorly soluble complex or a poorly soluble salt) of the organic acid, followed by removal of the precipitated metal compound of the organic acid by solid-liquid separation. Among the metal ions that can be used according to the present invention, Fe 2+ and Cu2+ is preferred (especially when obtaining an aliphatic saturated dicarboxylic acid), and particularly preferred is Cu 2+ is (again, especially when obtaining an aliphatic saturated dicarboxylic acid).

[0079] The optimum pH in step B) is derived from the type of organic acid obtained. In the case of aminobenzoic acid of formula (I), it is preferably 3.0 to 4.7, more preferably 3.2 to 3.7, and most preferably 3.4 to 3.6. In the case of an aliphatic saturated dicarboxylic acid of formula (II), it is preferably above 4.0 to 7.0, more preferably 4.7 to 5.8, and most preferably 5.3 to 5.7. If there is a risk that the pH may deviate from the target range due to the acidic or basic properties of the added metal salt, this can be easily corrected by the addition of an acid (preferably hydrochloric acid, sulfuric acid, nitric acid or phosphoric acid) or a base (preferably a sodium hydroxide solution, a potassium hydroxide solution or calcium hydroxide).

[0080] The metal salt used in step B) is preferably a sulfate, a chloride and / or a hydroxide. The use of a hydroxide enables a particularly economically viable configuration of the process of the invention in which the precipitated metal hydroxide obtained in step C) described hereinafter is returned to step B) and is used as a constituent of the metal salt. An excessive increase in the pH in step B) can be offset by the addition of an acid.

[0081] The metal ions of the metal salt are preferably added in a sub-stoichiometric amount based on the amount of the organic acid.

[0082] The metal salt treatment is preferably carried out at 20°C to 50°C, more preferably 20°C to 30°C, and particularly preferably at ambient temperature. An example of a suitable reactor is a stirred tank reactor (or, in particular, two or more stirred tank reactors connected in series). The procedure for carrying out the treatment may be such that the metal salt (e.g., Cu(OH)2) is first charged into the reactor and mixed with an aqueous solution of an organic acid while actively adjusting the pH as necessary (see the above details regarding the preferred pH values). After precipitation of the metal compound of the poorly soluble organic acid, it is separated by solid-liquid phase separation. The remaining aqueous phase can be disposed of as wastewater. This aqueous phase still contains a fraction of the metal salt corresponding to its solubility at the current (acidic, see above) pH, and these proportions may be undesirably high from an environmental point of view. Therefore, in a preferred embodiment of the present invention, in order to precipitate the dissolved metal ions as a poorly soluble hydroxide, the pH of the aqueous liquid phase obtained in the solid-liquid phase separation must be raised to a value of 8.0 to 14, preferably 10 to 13. These are then separated in a second solid-liquid phase separation and can be reused in step B). The aqueous liquid phase obtained in the second solid-liquid phase separation can then be disposed of without difficulty, for example, in a biological treatment plant. Suitable bases for raising the pH are standard bases such as alkali metal and alkaline earth metal hydroxides, alkali metal and alkaline earth metal carbonates, or alkali metal and alkaline earth metal hydrogen carbonates, particularly sodium hydroxide solution, potassium hydroxide solution, or calcium hydroxide solution.

[0083] Base treatment In step C) of the method of the present invention, the base treatment of the metal compound of the organic acid obtained in step B) is carried out. The organic acid is here in anionic form and in solution, and the metal ions used precipitate as hydroxides.

[0084] Step C) is preferably carried out in multiple stages of n consecutive steps, where n is a natural number in the range of 2 to 10, preferably 3 to 9, and more preferably 4 to 8. For this purpose, in each of the n steps, a part of the metal compound of the removed organic acid is treated with an aqueous base solution to precipitate a metal hydroxide. Subsequently, after each step, the precipitated metal hydroxide is removed by solid-liquid separation, leaving an aqueous basic solution containing the anion of the organic acid. The aqueous base solutions in the second to nth steps each contain (optionally, consist of, i.e., contain no further optional components) the aqueous basic solution containing the anion of the organic acid obtained in the respective previous step. The crystallization according to step D), which will be described in detail below, is carried out with the aqueous basic solution containing the anion of the organic acid obtained in the nth step of C).

[0085] In step C), it is preferred that a pH in the range of 9.0 to 14, preferably 10 to 14, and more preferably 11 to 13 is observed, and a base solution is further metered in as required. Suitable aqueous base solutions are, in particular, aqueous solutions of alkali metal or alkaline earth metal hydroxides (in particular sodium hydroxide solution, potassium hydroxide solution or calcium hydroxide solution (aqueous solution of calcium hydroxide)), alkali metal or alkaline earth metal hydrogen carbonates, alkali metal or alkaline earth metal carbonates (in particular sodium hydrogen carbonate solution or potassium hydrogen carbonate solution, or sodium carbonate solution or potassium carbonate solution), or mixtures of two or more of the above-mentioned base solutions, i.e., all bases well known to those skilled in the art. Sodium hydroxide solution and potassium hydroxide solution are particularly preferred. In the case of a multi-stage implementation of step C), the pH values mentioned are observed in each of the n steps.

[0086] Step C) is preferably carried out at ambient temperature, as in step B). Again, a stirred tank reactor is suitable (or, in particular, two or more stirred tank reactors connected in series).

[0087] Crystallization In step D), the anions of the organic acids present in the basic aqueous solution obtained in step C) are crystallized. This is achieved by lowering the pH by adding an inorganic acid, in particular hydrochloric acid, sulfuric acid, nitric acid or phosphoric acid. The simplest means of carrying out step D) is to introduce the basic aqueous solution obtained in step C) into the crystallization according to A)α) in which the corresponding acidic conditions already exist. However, it is of course also possible to carry out step D) separately from A)α), for example in a separate crystallization apparatus. Suitable types for this purpose are those as described above and, optionally, of a smaller design (due to the low amounts). Next, the pH value has to be adjusted as further described above for A)α).

[0088] The attached figures are intended to enhance the understanding of the present invention.

[0089] Figure 1 shows a preferred embodiment of the method according to the invention, where step Aα) is a downstream step of the actual preparation of the organic acid, and step D) is carried out in which the aqueous solution containing the anions of the organic acid from step C) is returned to the crystallization according to A)α).

[0090] The reference signs have the following meanings.

[0091] [Table 1]

[0092] Figure 2 shows a preferred configuration of step C) in n steps (here, as an example, n = 7). Here, the metal compound (9) of the organic acid obtained in step B) is divided into seven parts (9.1, 9.2,... 9.7), and the first part (9.1) is treated with an aqueous base solution (10). After solid-liquid separation, the first part (12.1) of the precipitated metal hydroxide (12) is obtained and removed (for clarity, the steps of base treatment and solid-liquid separation are not described separately here). The remaining basic aqueous liquid phase is added to the second part (9.2) of the metal compound, and another solid-liquid separation is performed to remove the second part (12.2) of the precipitated metal hydroxide (12). After these steps are performed on the further five parts of the metal compound of the organic acid, a basic aqueous solution (13) containing the anion of the organic acid is finally obtained. The obtained parts (12.1, 12.2,... 12.7) of the precipitated metal hydroxide are preferably mixed and then fed to the metal salt treatment in step B) as shown in Figure 1.

Example

[0093] The following examples were not prepared specifically for the examples but were carried out with organic acids obtained from commercial suppliers. Therefore, the aqueous solution of the organic acid obtained in step A) of the method of the present invention was artificially prepared, but this does not impair the significance of the experiment.

[0094] Example 1: Precipitation of 2-aminobenzoic acid in an aqueous solution by addition of CuSO4, FeSO4 or MnSO4 Chemical substances: 2-aminobenzoic acid (anthranilic acid, ortho-aminobenzoic acid; CAS number: 118-92-3) was obtained from Sigma-Aldrich with a purity of 98% or more. 2-aminobenzoic acid is hereinafter abbreviated as "oAB" regardless of its existing form (electrically neutral or as an anion). CuSO4, FeSO4·7H2O and MnSO4·H2O were obtained from Sigma-Aldrich with a purity of 99% or more. Ultra-pure water (prepared with a Millipore laboratory water treatment system) was used. NaOH (pellets) and HCl (aqueous solution) (37% strength) were of Acros manufacture.

[0095] Experiment: a) Preparation of aqueous solution of organic acid An aqueous oAB solution (oAB concentration 5 g / L) was prepared by dissolving oAB in water, and in this way, an aqueous solution of the organic acid obtained by crystallization in step A)α) (= mother liquor of crystallization) was artificially formulated.

[0096] b) Treatment of the aqueous solution of organic acid with metal salts (step B)) The oAB aqueous solution and metal salts (CuSO4, FeSO4 or MnSO4) were mixed at room temperature for at least 30 minutes (molar ratio of metal salt: oAB = 1:2). The pH was adjusted to about 3.5 with 1M NaOH solution (corresponding to the isoelectric point of oAB). Subsequently, it was waited for 30 minutes until the formed solid (metal compound of organic acid) was completely sedimented. A sample of the aqueous supernatant was analyzed by HPLC (high performance liquid chromatography) with respect to the oAB concentration (sample A). The solid (Cu(oAB)2, Fe(oAB)2 and / or Mn(oAB)2) was separated from the liquid phase by centrifugation.

[0097] c) Base treatment of the removed metal compound of organic acid (step C)) In the case of experiments using Fe and Cu, the removed solid was resuspended in water and the pH was adjusted to pH = 12.0 - 12.5 with 1M NaOH solution. The oAB metal compound became a solution state, and metal hydroxides (Cu(OH)2 and / or Fe(OH)2) precipitated in solid form. After mixing for 30 minutes and a sedimentation time of 30 minutes, a sample of the aqueous supernatant was analyzed by HPLC for oAB (sample B). Thereafter, the solid (precipitated metal hydroxide) was separated from the liquid phase (basic aqueous solution containing anions of organic acid). In the case of iron(II) hydroxide, the base treatment was repeated (see Figure 2).

[0098] An attempt was made to further increase the oAB concentration in the liquid phase by repeated addition of Fe(oAB)2 (a total of 7 additions). In each of the 7 steps, Fe(OH)2 precipitated in solid form and was removed by centrifugation after each addition.

[0099] d) Recycling of the precipitated metal hydroxide into the treatment step with a metal salt of an aqueous solution of an organic acid An oAB aqueous solution (5 g / L) was mixed with a solid metal hydroxide at pH = 3.5 for 30 minutes. The metal hydroxide dissolved and Cu(oAB)2 and / or Fe(oAB)2 precipitated. After the solid settled, the liquid phase sample was analyzed for oAB content using HPLC analysis (Sample C).

[0100] High Performance Liquid Chromatography: An Agilent 1260 Infinity II LC with a diode array detector was used for the quantification of oAB. The stationary phase used was a C18 Zorbax Eclipse (4.6×150 mm) with a pre-column. The mobile phases used were water (A) containing 0.1% H3PO4 and methanol (B), and the following linear gradient was used. 0 min: 95% A / 5% B 4 min: 95% A / 5% B 15 min: 2% A / 98% B 16 min: 2% A / 98% B 16.5 min: 95% A / 5% B 21 min: 95% A / 5% B

[0101] The volumetric flow rate was set at 0.5 mL / min. A 5 μL sample was injected each time. The column temperature was 35 °C. oAB was detected at wavelengths of 254 nm and 330 nm and compared with the calibration curve.

[0102] Results: Sample A) from the aqueous supernatant (b) after precipitation of the metal compound of the organic acid had an oAB concentration of less than the detection limit of 0.05 g oAB / L. This indicates that it was possible to precipitate oAB substantially quantitatively (more than 99%) in solid form in the form of the oAB-metal compound.

[0103] Sample B) from the aqueous supernatant (c) after precipitation of the metal hydroxide caused by base treatment showed an oAB concentration of 14 g / L. In the case of iron, by carrying out the base treatment in 7 steps, it was possible to increase the oAB concentration in the liquid phase up to 301 g / L.

[0104] The solid (precipitated metal hydroxide, Cu(OH)2 and / or Fe(OH)2) was shown to be reusable for complex formation of oAB from the aqueous solution (see (d)). Similar to sample A from (b), in sample C after addition of both Fe(OH)2 and Cu(OH)2, an oAB concentration of less than 0.05 g oAB / L was measured.

[0105] Overall, it can be said that by the treatment with a series of metal salts and base treatment of the present invention, it was possible to clearly concentrate the oAB present in the original "aqueous solution of organic acid" (5 g / L) (at least 14 g / L, 301 g / L in the case of base treatment in 7 steps). The thus-obtained clearly concentrated (of the anions of oAB) solution can be used without any problem for the crystallization step (step D)) aimed at the isolation of oAB.

[0106] Example 2: Precipitation of adipic acid in an aqueous solution by addition of CuSO4 Chemicals: Adipic acid (CAS number: 124 - 04 - 9) was obtained with a purity of 98%. CuSO4 was obtained from Sigma - Aldrich with a purity of over 99%. Ultra - pure water (prepared with a Millipore laboratory water treatment system) was used. NaOH (pellets) and HCl (aqueous solution) (37% strength) from Acros were used.

[0107] Experiment: a) Preparation of an aqueous solution of the organic acid An aqueous adipic acid solution (12 g / L) was prepared by dissolving adipic acid in water, and thus, the aqueous solution of the organic acid obtained by crystallization in step A)α) (= mother liquor of crystallization) was artificially formulated.

[0108] b) Treatment with a metal salt of an aqueous solution of an organic acid (Step B)) An aqueous solution of adipic acid and a metal salt (CuSO4) were mixed at room temperature for at least 30 minutes (molar ratio of metal salt:adipic acid = 1:1). The pH was adjusted to approximately 5.5 with 1M NaOH solution. Subsequently, it was waited for 30 minutes until the formed solid (metal compound of the organic acid) completely settled. A sample of the aqueous supernatant was analyzed by HPLC (high performance liquid chromatography) for adipic acid concentration (Sample A).

[0109] The solid (copper adipate) was separated from the liquid phase by centrifugation.

[0110] c) Base treatment of the removed metal compound of the organic acid (Step C)) The removed solid was resuspended in water and the pH was adjusted to 12 - 12.5 with 1M NaOH solution. The adipic acid - metal compound became a solution state and metal hydroxide (Cu(OH)2) precipitated. It was mixed for 30 minutes and after a sedimentation time of 30 minutes, a sample of the aqueous supernatant was analyzed by HPLC for adipic acid content (Sample B).

[0111] Subsequently, the solid (precipitated metal hydroxide) was separated from the liquid phase (basic aqueous solution containing the anion of the organic acid).

[0112] d) Use of the precipitated metal hydroxide in the treatment step with a metal salt of an aqueous solution of an organic acid An aqueous solution of adipic acid (12 g / L) was mixed with the metal hydroxide (approximately stoichiometrically) at pH = 4.5 for 30 minutes. The metal hydroxide dissolved and metal adipate precipitated. After the solid settled, a sample of the liquid phase was analyzed for adipic acid content using HPLC analysis (Sample C).

[0113] High performance liquid chromatography: Samples were prepared in 0.1M aqueous phosphate buffer containing 0.1 wt% pimelic acid.

[0114] The Agilent 1260 Infinity II LC with a diode array detector was used for the quantification of adipic acid. The stationary phase used was C18 Zorbax Eclipse (4.6×150 mm) with a precolumn (Poroshell 120 EC-C18 (4.6×5 mm)). The mobile phase used was water (A) and acetonitrile (B) containing 0.1% H3PO4, and the following linear gradient was used. 0 min: 95% A / 5% B 0.5 min: 95% A / 5% B 4.5 min: 75% A / 25% B 6.5 min: 75% A / 25% B 6.6.5 min: 95% A / 5% B 9.5 min: 95% A / 5% B

[0115] The volumetric flow rate was set at 1.5 mL / min. A 1 μL sample was injected each time. The column temperature was 35 °C. Adipic acid was detected at a wavelength of 208.8 nm and compared with a calibration curve.

[0116] Results: Sample A) from the aqueous supernatant (b) after precipitation of the metal compound of the organic acid had an adipic acid concentration of 0.99 g / L. This indicates a low solubility of the salt.

[0117] Sample B) from the aqueous supernatant (c) after precipitation of the metal hydroxide caused by base treatment showed an adipic acid concentration of 24 g / L.

[0118] The solid (precipitated Cu(OH)2) was shown to be reusable for the precipitation of adipic acid from the aqueous solution (see (d)). The adipic acid concentration in sample C from (d) was 3 g / L. Based on the current data, this value is expected to still be able to be reduced when (d) is carried out at pH = 5.5.

[0119] As a whole, it can be said that by a series of treatments with metal salts and base treatment of the present invention, it was possible to clearly concentrate adipic acid present in the original "aqueous solution of organic acid" (12 g / L) (at least 24 g / L). The thus-obtained clearly concentrated (adipate) solution can be used without any problem in the crystallization step (step D)) for the purpose of isolating adipic acid.

[0120] Example 3: Precipitation of 2-amino-5-methylbenzoic acid in an aqueous solution by addition of CuSO4 Chemical substances: 2-Amino-5-methylbenzoic acid (CAS number: 2941-78-8) was obtained from Sigma-Aldrich with a purity of 97%. CuSO4 was obtained from Sigma-Aldrich with a purity of over 99%. Ultra-pure water (prepared with a Millipore laboratory water treatment system) was used. NaOH (pellets) and HCl (aqueous solution) (37% strength) were of Acros make.

[0121] Experiment: a) Preparation of an aqueous solution of an organic acid An aqueous solution of 2-amino-5-methylbenzoic acid (1 g / L) was prepared by dissolving 2-amino-5-methylbenzoic acid in water, and thus an aqueous solution of the organic acid (= mother liquor of crystallization) obtained by crystallization in step A)α) was artificially prepared.

[0122] b) Treatment of the aqueous solution of the organic acid with a metal salt (step B)) The aqueous solution of 2-amino-5-methylbenzoic acid and the metal salt (CuSO4) were mixed at room temperature for at least 30 minutes (metal salt: 2-amino-5-methylbenzoic acid = 1:1 molar ratio). The pH was set to 3.5 with NaOH. Subsequently, it was waited for 30 minutes until the formed solid (metal compound of the organic acid) completely settled. A sample of the aqueous supernatant was analyzed by HPLC (high performance liquid chromatography) for the 2-amino-5-methylbenzoic acid concentration (sample A).

[0123] The solid (copper 2-amino-5-methylbenzoate) was separated from the liquid phase. A centrifuge was used for better solid-liquid separation.

[0124] c) Base treatment of the metal compound of the removed organic acid (Step C)) The removed solid was resuspended in water and the pH was adjusted to 12.5 with 1M NaOH solution. The 2-amino-5-methylbenzoic acid-metal compound went into solution and the metal hydroxide (Cu(OH)2) precipitated. It was mixed for 30 minutes and after a sedimentation time of 30 minutes, a sample of the aqueous supernatant was analyzed by HPLC for 2-amino-5-methylbenzoic acid content (Sample B).

[0125] High performance liquid chromatography: An Agilent 1260 Infinity II LC with a diode array detector was used for the quantification of 2-amino-5-methylbenzoic acid. The stationary phase used was a C18 Zorbax Eclipse (4.6×150mm) with a precolumn. The mobile phases used were water containing 0.1% H3PO4 (A) and methanol (B), and the following linear gradient was used. 0 min: 95% A / 5% B 4 min: 95% A / 5% B 15 min: 2% A / 98% B 16 min: 2% A / 98% B 16.5 min: 95% A / 5% B 21 min: 95% A / 5% B

[0126] The volumetric flow rate was set at 0.5 mL / min. A 5 μL sample was injected each time. The column temperature was 35 °C. 2-Amino-5-methylbenzoic acid was detected at wavelengths of 254 nm and 330 nm and compared with the calibration curve.

[0127] Results: Sample A) from the aqueous supernatant (b) after precipitation of the metal compound of the organic acid had a 2-amino-5-methylbenzoic acid concentration of less than 0.01 g / L. This indicates the low solubility of the metal compound.

[0128] Sample B) from the aqueous supernatant (c) after precipitation of the metal hydroxide caused by the base treatment showed a 2-amino-5-methylbenzoic acid concentration of 0.72 g / L.

[0129] Overall, it can be said that by the treatment with a series of metal salts of the present invention and the base treatment, 2-amino-5-methylbenzoic acid present in the original "aqueous solution of organic acid" (1 g / L) was separated from the aqueous solution and then it was possible to redissolve it in water. It is expected that a clear concentration of the 2-amino-5-methylbenzoic acid concentration (similar to Example 1) can be achieved. Concentration was not performed in this example. The thus obtained (2-amino-5-methylbenzoic acid) solution can be used without any problem for the crystallization step (Step D)) aimed at the isolation of 2-amino-5-methylbenzoic acid.

Claims

Claim 1 A method for obtaining an organic acid from an aqueous solution of the organic acid, wherein the organic acid is (i) of the formula: 【Chemical 1】 (wherein R is CH ３ or H), aminobenzoic acid, or (ii) of the formula: 【Chemical Formula 2】 (wherein n = 1 or 2) selected from aliphatic saturated dicarboxylic acids, The method comprises A) a step of preparing the organic acid by a biological process or a chemical reaction, wherein α) the organic acid is crystallized from an aqueous medium during or after the preparation, Subsequently, 1) removing the fraction of the organic acid precipitated in the crystallization by solid-liquid separation to leave a first aqueous solution of the organic acid, 2) Optionally, the fraction of the organic acid dissolved in the first aqueous solution of the organic acid is extracted with an organic extractant for the organic acid or depleted by adsorbing the organic acid onto an adsorbent, Subsequently, removing the organic extractant or the adsorbent to obtain a second aqueous solution of the organic acid, a step; Subsequently, a step of removing the metal compound of the precipitated organic acid by solid-liquid separation; B) An aqueous solution of the first organic acid or an aqueous solution of the second organic acid is treated with a metal salt containing metal ions of Mn ２＋ , Fe ２＋ and / or Cu ２＋ to precipitate a metal compound of the organic acid, C) a step of subjecting the removed metal compound of the organic acid to a base treatment with an aqueous base solution to precipitate a metal hydroxide, and removing the precipitated metal hydroxide by solid-liquid separation to leave a basic aqueous solution containing the anion of the organic acid; D) a step of crystallizing the organic acid by adding an inorganic acid from the basic aqueous solution containing the anion of the organic acid obtained in C); A method comprising Claim 2 The base treatment in C) includes n steps that are carried out continuously, where n is a natural number in the range of 2 to 10, In each of the n steps, a part of the removed metal compound of the organic acid is treated with an aqueous base solution to precipitate a metal hydroxide, and following each step, the precipitated metal hydroxide is removed by solid-liquid separation to leave a basic aqueous solution containing the anion of the organic acid, and the aqueous base solution in the second to nth steps includes the basic aqueous solution containing the anion of the organic acid obtained in the respective previous steps, The crystallization of the organic acid in D) is carried out with the basic aqueous solution containing the anion of the organic acid obtained in the nth step of C), according to the method of claim 1. Claim 3 The crystallization of the organic acid in D) includes recycling the basic aqueous solution containing the anion of the organic acid obtained in C) to A) α), or alternatively, The crystallization of the organic acid in D) is carried out separately from A) α), according to the method of claim 1 or 2. Claim 4 ​ The method according to any one of claims 1 to 3, wherein the metal hydroxide precipitated in C) is reused in step B) and used as a constituent of the metal salt.

5. The method according to any one of claims 1 to 4, wherein the organic acid is an aminobenzoic acid of formula (I).

6. The method according to claim 5, wherein the aminobenzoic acid of formula (I) is 2-aminobenzoic acid or 2-amino-5-methylbenzoic acid.

7. The method according to claim 5 or 6, wherein in A) α), a pH in the range of 3.0 to 4.7 is established by addition of an inorganic acid, and a pH within the same range is maintained in B).

8. The method according to any one of claims 5 to 7, wherein A) comprises a biological process comprising fermentation of a raw material containing a fermentable carbon-containing compound and a nitrogen-containing compound in the presence of microorganisms.

9. The method according to any one of claims 5 to 7, wherein A) comprises a chemical conversion.

10. The method according to claim 9, wherein A) comprises a reaction of an optionally methyl-substituted phthalimide or phthalamide with an alkali metal hypohalite in a basic medium, followed by addition of an inorganic acid for carrying out A) α).

11. The method according to any one of claims 1 to 4, wherein the organic acid is an aliphatic saturated dicarboxylic acid of formula (II).

12. The method according to claim 11, wherein the aliphatic saturated dicarboxylic acid of formula (II) is hexane-1,6-dicarboxylic acid.

13. The method according to claim 11 or 12, wherein in A) α), a pH in the range of 0 to 4.0 is established by addition of an inorganic acid, and in B), a pH in the range of greater than 4.0 to 7.0 is established by addition of a base.

14. The method according to any one of claims 11 to 13, wherein A) comprises a biological process.

15. The method according to claim 14, wherein the biological process comprises fermentation of a raw material containing a fermentable carbon-containing compound in the presence of microorganisms.

16. The method according to any one of claims 11 to 13, wherein A) comprises a chemical conversion.

17. A) comprises hydrogenation of an aliphatic unsaturated dicarboxylic acid corresponding to the aliphatic saturated dicarboxylic acid of formula (II), or, The aliphatic saturated dicarboxylic acid of formula (II) is hexane-1,6-dicarboxylic acid, and the method according to claim 16, wherein A) comprises oxidizing cyclohexane with oxygen or an oxygen-containing gas mixture to cyclohexanol and cyclohexanone, and subsequently oxidizing them with nitric acid.

18. The method according to claim 14 or 16, wherein A) comprises cleavage of the polyester.

19. The metal ion of the metal salt used in B) is Fe ２＋ and / or Cu ２＋ The method according to any one of claims 1 to 18, comprising.

20. The method according to any one of claims 1 to 19, wherein a pH in the range of 9.0 to 14 is established in C).

21. The method according to any one of claims 1 to 20, wherein the metal ions are added in a sub-stoichiometric amount in B) based on the amount of the organic acid.

22. The method according to any one of claims 1 to 21, wherein the metal salt comprises a sulfate, a chloride and / or a hydroxide.

23. Removal of the metal compound of the precipitated organic acid by solid-liquid phase separation in B) leaves an aqueous phase adjusted to a pH in the range of 8.0 to 14 by addition of a base, precipitating a metal hydroxide, which is removed by further solid-liquid phase separation, and then used as a constituent of the metal salt in B). The method according to any one of claims 1 to 22.

Images