阅读说明：本技术 制备氨基苯甲酸或氨基苯甲酸反应产物的方法 (Process for preparing aminobenzoic acid or aminobenzoic acid reaction products ) 是由 W·克勒克纳 F·贝格尔 G·耶格尔 S·克拉夫尔 G·奥夫 于 2019-06-05 设计创作，主要内容包括：本发明涉及使用发酵法制备氨基苯甲酸或氨基苯甲酸反应产物的方法,其中(I)在通过发酵获得的发酵液中形成的氨基苯甲酸部分地,任选由于溶解平衡而尽可能地,结合为不溶性氨基苯甲酸钙,所述不溶性氨基苯甲酸钙然后(II)独自地或作为与发酵中所用的微生物的混合物分离出来,并转化成水溶性形式并析出不同于氨基苯甲酸钙的不溶性钙盐,然后(III)通过将二氧化碳在压力下引入已脱除沉淀钙盐的水溶液而使氨基苯甲酸沉淀。(The invention relates to a method for producing aminobenzoic acid or aminobenzoic acid reaction products using a fermentation process, wherein (I) aminobenzoic acid formed in a fermentation broth obtained by fermentation is partially, optionally as far as possible due to the solubility equilibrium, bound as insoluble calcium aminobenzoate, which is then (II) isolated alone or as a mixture with microorganisms used in the fermentation and converted into a water-soluble form and an insoluble calcium salt different from the calcium aminobenzoate is precipitated, and then (III) aminobenzoic acid is precipitated by introducing carbon dioxide under pressure into an aqueous solution from which the precipitated calcium salt has been removed.)

1. A process for preparing an aminobenzoic acid or aminobenzoic acid reaction product comprising the steps of:

(I) fermenting a raw material in a fermentation reactor using a microorganism and a calcium salt, comprising at least

● it is possible to ferment carbon-containing compounds, preferably starch hydrolysates, sugar cane juice, beet juice, hydrolysates of lignocellulose-containing raw materials or mixtures thereof,

and

● Nitrogen-containing compounds, preferably gaseous ammonia, aqueous ammonia, ammonium salts, urea or mixtures thereof,

thereby obtaining a mixture suspended in the aqueous fermentation solution comprising undissolved microorganisms and precipitated calcium aminobenzoate;

(II) (1) isolation of the aqueous fermentation solution obtained in step (I)

(1) (i) precipitating calcium aminobenzoate or

(1) (ii) a mixture comprising undissolved microorganisms and precipitated calcium aminobenzoate,

(2) converting the aminobenzoate group bound in the calcium aminobenzoate to a water-soluble form and forming a water-insoluble calcium salt different from the calcium aminobenzoate by adding an aqueous phase containing a water-soluble aminobenzoate-forming cation and a water-insoluble calcium salt-forming anion to the separated calcium aminobenzoate from (1) (i) or to a mixture comprising undissolved microorganisms and precipitated calcium aminobenzoate from (1) (ii),

thus obtaining a suspension comprising, in an aqueous solution of aminobenzoate

(2) (i) precipitation of water-insoluble calcium salts or

(2) (ii) a mixture comprising undissolved microorganisms and a water-insoluble calcium salt,

(3) separating the aqueous solution of aminobenzoate obtained in step (2) from the precipitated water-insoluble calcium salt from (2) (i) or from the mixture comprising undissolved microorganisms and water-insoluble calcium salt from (2) (ii);

(III) at 1.50 bar or more_(Absolute)Introducing carbon dioxide into the aqueous solution of aminobenzoate separated in step (II) (3) at a pressure to precipitate aminobenzoic acid, thereby forming a suspension containing aminobenzoic acid in the aqueous solution;

(IV) separating the aminobenzoic acid precipitated in step (III) comprising reducing the pressure to release carbon dioxide, wherein an aqueous solution is obtained with a reduced carbon dioxide content and with removal of precipitated aminobenzoic acid;

(V) using the aqueous solution reduced in carbon dioxide content and freed from aminobenzoic acid obtained in step (IV) as a component of the aqueous phase added in step (II) (2);

(VI) optionally further reacting the aminobenzoic acid separated in step (IV) (1) to an aminobenzoic acid reaction product, wherein step (VI) preferably comprises one of the following reactions:

(1) decarboxylating aminobenzoic acid to produce aniline;

(2) decarboxylating aminobenzoic acid to produce aniline followed by an acid-catalyzed reaction of aniline with formaldehyde to form di-and polyamines of the diphenylmethane series;

(3) decarboxylating aminobenzoic acid to produce aniline, followed by an acid-catalyzed reaction of aniline with formaldehyde to form di-and polyamines of the diphenylmethane series, followed by reaction with phosgene to form di-and polyisocyanates of the diphenylmethane series;

(4) decarboxylating aminobenzoic acid to produce aniline, followed by conversion of the aniline to an azo compound;

(5) converting aminobenzoic acid to an amide;

(6) aminobenzoic acid is converted to a conductive polymer, for example, preferably poly-anthranilic acid.

2. The process as claimed in claim 1, wherein the calcium salt used in step (I) is selected from calcium carbonate, calcium bicarbonate, calcium hydroxide, calcium oxide and mixtures thereof.

3. A process as claimed in claim 1 or 2, wherein the aqueous phase added in step (II) (2) comprises

Lithium, sodium, potassium and/or ammonium cations, preferably ammonium cations, and

carbonate and/or bicarbonate anions.

4. A process as claimed in any one of the preceding claims, wherein the fermentation in step (I) is carried out discontinuously in the fermentation cycle.

5. A process as claimed in claim 4, wherein, after the end of the fermentation cycle,

(A)

performing step (II) (1) by draining the aqueous fermentation solution obtained in step (I) from the fermentation reactor and retaining the mixture comprising undissolved microorganisms and precipitated calcium aminobenzoate suspended therein;

step (II) (2) is carried out by introducing the aqueous phase into a fermentation reactor to obtain a suspension in the fermentation reactor, the suspension containing, in an aqueous solution of aminobenzoate, a mixture comprising undissolved microorganisms and a water-insoluble calcium salt;

and

step (II) (3) is carried out by discharging from the fermentation reactor the aqueous solution of aminobenzoate obtained in step (II) (2), wherein the mixture comprising undissolved microorganisms and water-insoluble calcium salts is retained and made available for the next fermentation cycle;

or

(B)

Step (II) (1) is carried out by discharging the aqueous fermentation solution obtained in step (I) together with the mixture comprising undissolved microorganisms and precipitated calcium aminobenzoate suspended therein from the fermentation reactor and separating the mixture comprising undissolved microorganisms and precipitated calcium aminobenzoate from the aqueous fermentation solution outside the fermentation reactor and recycling to the fermentation reactor;

step (II) (2) is carried out by introducing the aqueous phase into a fermentation reactor to obtain a suspension in the fermentation reactor, the suspension containing, in an aqueous solution of aminobenzoate, a mixture comprising undissolved microorganisms and a water-insoluble calcium salt;

and

step (II) (3) is carried out by discharging from the fermentation reactor the aqueous solution of aminobenzoate obtained in step (II) (2), wherein the mixture comprising undissolved microorganisms and water-insoluble calcium salts is retained and made available for the next fermentation cycle;

or

(C)

Performing step (II) (1) by discharging the aqueous fermentation solution obtained in step (I) together with the mixture comprising undissolved microorganisms and precipitated calcium aminobenzoate suspended therein from the fermentation reactor and separating the mixture comprising undissolved microorganisms and precipitated calcium aminobenzoate from the aqueous fermentation solution outside the fermentation reactor and introducing into a vessel different from the fermentation reactor;

step (II) (2) is carried out by introducing the aqueous phase into such a vessel to obtain in such a vessel a suspension containing, in an aqueous solution of aminobenzoate, a mixture comprising undissolved microorganisms and a water-insoluble calcium salt;

and

after the aqueous solution of aminobenzoate obtained in step (II) (2) is separated from the mixture comprising undissolved microorganisms and water-insoluble calcium salts in step (II) (3), this separated mixture is returned to the fermentation reactor and made available for the next fermentation cycle in step (II) (4).

6. A process as claimed in claim 5, wherein steps (I) and (II) are repeated until the desired amount of aminobenzoic acid is obtained in step (IV) or the microorganism used in step (I) has to be replaced.

7. A process as claimed in any one of claims 1 to 3, wherein the fermentation in step (I) is carried out continuously.

8. The method as claimed in claim 7, wherein

(A)

Continuously discharging from the fermentation reactor a mixture suspended in the aqueous fermentation solution and comprising undissolved microorganisms and precipitated calcium aminobenzoate, and

performing step (II) (1) by separating the insoluble microorganisms and the precipitated calcium aminobenzoate from each other and from the aqueous fermentation solution after performing the draining;

step (II) (2) is carried out by adding an aqueous phase to the thus separated calcium aminobenzoate;

and wherein the insoluble microorganisms separated in step (II) (1) are partially to completely recycled to the fermentation reactor;

or therein

(B)

Continuously discharging from the fermentation reactor the precipitated calcium aminobenzoate suspended in the aqueous fermentation solution with entrapment of undissolved microorganisms, and

performing step (II) (1) by separating the precipitated calcium aminobenzoate from the aqueous fermentation solution after performing the draining;

step (II) (2) is carried out by adding an aqueous phase to the thus separated calcium aminobenzoate;

or therein

(C)

Continuously discharging from the fermentation reactor a mixture suspended in the aqueous fermentation solution and comprising undissolved microorganisms and precipitated calcium aminobenzoate, and

performing step (II) (1) by separating the mixture comprising undissolved microorganisms and precipitated calcium aminobenzoate from the aqueous fermentation solution after performing the draining;

step (II) (2) is carried out by adding an aqueous phase to this mixture thus separated;

and

after separating the aqueous solution of aminobenzoate obtained in step (II) (2) from the mixture comprising undissolved microorganisms and water-insoluble calcium salts in step (II) (3), this separated mixture is returned to the fermentation reactor and made available for further continuous fermentation in step (II) (4);

or therein

(D)

Continuously discharging from the fermentation reactor a mixture suspended in the aqueous fermentation solution and comprising undissolved microorganisms and precipitated calcium aminobenzoate, and

performing step (II) (1) by separating the mixture comprising undissolved microorganisms and precipitated calcium aminobenzoate from the aqueous fermentation solution after performing the draining;

step (II) (2) is carried out by adding an aqueous phase to this mixture thus separated;

and

after the aqueous solution of aminobenzoate obtained in step (II) (2) has been separated from the mixture comprising undissolved microorganisms and water-insoluble calcium salt in step (II) (3), this separated mixture is separated in step (II) (4a) into the components undissolved microorganisms and water-insoluble calcium salt, and one of these components separated from one another, preferably the water-insoluble calcium salt, is returned in step (II) (4b) to the fermentation reactor and made available for further continuous fermentation, wherein preferably fresh microorganisms are added to the fermentation reactor.

9. A method as claimed in any one of the preceding claims, wherein

(A)

Crystallizing aminobenzoic acid from the aqueous fermentation solution obtained in step (II) (1) by adding an acid until a pH value of 3.0 to < 4.0 is reached and isolating the crystallized aminobenzoic acid, wherein a mother liquor with a reduced aminobenzoic acid content is left;

or therein

(B)

Recycling the aqueous fermentation solution obtained in step (II) (1) to the fermentation of step (I).

10. The method as claimed in any one of the preceding claims, wherein step (IV) comprises the sub-steps of:

(1) separating the precipitated aminobenzoic acid from step (III) and the aqueous solution at a pressure equal to or greater than the pressure in step (III),

(2) decompressing the aqueous solution separated in step (1) to release carbon dioxide, thereby obtaining an aqueous solution with a reduced carbon dioxide content.

11. A process as claimed in any one of the preceding claims wherein the water-insoluble calcium salt from (2) (I) or the mixture comprising undissolved microorganisms and water-insoluble calcium salt from (2) (II) separated in step (II) (3) is recycled to step (I).

12. A process as claimed in any one of the preceding claims wherein the carbon dioxide released in step (IV) is collected and used in step (III).

13. The method as claimed in any of the preceding claims, wherein in step (I) use is made of a compound selected from the group consisting ofEscherichia coli and foul odor Pseudomonas, Corynebacterium glutamicum, Ashbya gossypii, Pichia pastoris, Hansenula polymorpha, yarrowia lipolytica Yeast (Yarrowia lipolytica), Zygosaccharomyces bailiiOrSaccharomyces cerevisiaePreferably only representatives of exactly one of these types are used.

14. A process as claimed in any one of the preceding claims, wherein step (I) is carried out at a pH of 4.0 or greater.

15. The method as claimed in any one of the preceding claims, wherein step (II) (2) is carried out at a pH value > 7.0.

Examples

For the sake of simplicity of language, mention is generally made below also of anthranilic acid, even if it is present partly or completely as an anion (aminobenzoate) due to the pH values present. When particular aminobenzoate compounds are mentioned, such as in particular precipitated calcium anthranilate or commercially available salts, this may be counter-acted.

The reagents used were:

oAB stock solution A stock solution of anthranilic acid having a concentration of 500 g/L was prepared by dissolving sodium anthranilate in water at pH 7.0

Ammonium stock solution 1 stock solution of ammonium carbonate at a concentration of 105 g/L

Ammonium stock solution 2 stock solution of ammonium carbonate with a concentration of 210 g/L

Fermentation broth by "General digestion of" on pages 35 and 36 of WO 2015/124687A 1Corynebacterium glutamicumFermentative preparation of anthranilic acid-producing bacteria as described in section ATCC13032 based strains; contains anthranilic acid with concentration of 13.0 g/L

Pre-culture medium I the medium contained 16 g/L soya peptone (Duchefa, Batch No. 021679.01), 10 g/L yeast extract (Gistex LS FERM Batch, AFG2D 10), 5 g/L NaCl and 15 g/L glucose dissolved in fully desalted water (autoclaved separately).

Pre-culture Medium II, which contained 40 g/L glucose (autoclaved separately), 20 g/L (NH) dissolved in completely desalted water₄)₂SO₄5 g/L urea, 42 g/L MOPS buffer, 5 g/L yeast extract (Gistex LS FERM Batch AFG2D 10), 1 g/L KH₂PO₄、1 g/L K₂HPO₄、0.25 g/L MgSO₄·7 H₂O、0.01 g/L CaCl₂2 mg/L biotin (1 mL/L of biotin stock solution with 2 g/L biotin added, sterilized by 0.2 μm filtration) and 1 mL of trace element stock solution (sterilized by 0.2 μm filtration)

Growth medium containing 20 g/L glucose (autoclaved alone), 5 g/L (NH) dissolved in complete desalting₄)₂SO₄、4 g/L KH₂PO₄、4 g/L K₂HPO₄、2 g/L MgSO₄·7 H₂O、0.04 g/L CaCl₂·2 H₂O, 5 g/L yeast extract (Gistex LS FERM Batch: AFG2D 10), 5 g/L polypropylene glycol 2000 (antifoam), 2 mg/L biotin (1 mL/L of biotin stock solution with 2 g/L biotin was added, sterilized by 0.2 μm filtration) and 10 mL of trace element stock solution (sterilized by 0.2 μm filtration).

Main Medium I the medium contained 40 g/L glucose (autoclaved alone), 3.6 g/L (NH) dissolved in complete desalting₄)₂CO₃、4 g/L KH₂PO₄、4 g/L K₂HPO₄、2 g/L MgSO₄·7 H₂O、0.04 g/L CaCl₂·2 H₂O, 1 g/L polypropylene glycol 2000 (antifoam), 2 mg/L biotin (1 mL/L of biotin stock solution with 2 g/L biotin was added, sterilized by 0.2 μm filtration) and 10 mL of trace element stock solution (sterilized by 0.2 μm filtration).

Main Medium II containing 40 g/L glucose (autoclaved alone), 10 g/L (NH) dissolved in complete desalting₄)₂CO₃、3.2 g/L K₂CO₃、2.25 g/L K₂HPO₄、2 g/L MgSO₄·7 H₂O、20 g/L CaCO₃1 g/L polypropylene glycol 2000 (antifoam), 2 mg/L biotin (1 mL/L of stock solution of biotin with 2 g/L biotin was added, sterilized by 0.2 μm filtration) and 10 mL of stock solution of trace elements (sterilized by 0.2 μm filtration)

10 g/L of microelement stock solution MnSO₄·H₂O、10 g/L FeSO₄·7 H2O、1 g/L ZnSO₄·7 H₂O、0.2 g/L CuSO₄·5 H2O、0.02 g/L NiCl₂6H 2O in water. The components were dissolved by adding HCl at pH 1.

glucose-Tryptophan stock solution 480 g/L glucose and 1.6 g/L Tryptophan in water

Glucose stock solution 600 g/L glucose solution was sterilized by autoclaving

Ammonia base according to NH₃Calculated concentration of 4.5 mol/L aqueous ammonia solution

Example 1 formation of insoluble calcium anthranilate in fermentation broth and salt exchange with ammonium ions Principle experiment for dissolving it

48.0 g of anhydrous calcium chloride was added to 1.00 l of fermentation broth. The pH was adjusted to a value of 7.0 by addition of hydrochloric acid. To this mixture was then added 100 g of anthranilic acid (dissolved in sodium hydroxide solution at pH 7.0) by adding 200 ml of oAB stock solution. Calcium anthranilate precipitated immediately. The concentration of dissolved anthranilic acid measured in the aqueous phase was 18.0 g/L. The solid component of the mixture was filtered off and dried at 80 ℃ for 48 hours. 110 g of dry solid are thus obtained. 20.0 g of this was added to 50.0 ml of ammonium stock solution 1, stirred and the concentration of dissolved anthranilic acid was determined. The latter was 146 g/L.

Example 2 formation of insoluble calcium anthranilate in Water and salt exchange with ammonium ions Principle of dissolution experiment

48.0 grams of anhydrous calcium chloride was added to 800 milliliters of water. The pH was adjusted to a value of 7.0 by addition of hydrochloric acid. To this mixture was then added 100 g of anthranilic acid (dissolved in sodium hydroxide solution at pH 7.0) by adding 200 ml of oAB stock solution. Calcium anthranilate precipitated immediately. The concentration of dissolved anthranilic acid measured in the aqueous phase was 18.0 g/L. The solid component of the mixture was filtered off and dried at 80 ℃ for 48 hours. 110 g of dry solid are thus obtained. 20.0 g of this was added to 25.0 ml of ammonium stock solution 2, stirred and the concentration of dissolved anthranilic acid was determined. The latter was 175 g/L.

EXAMPLE 3 principle experiment for determining the solubility of calcium anthranilate in Water

3.00 g of dry calcium anthranilate were stirred into 100 ml of complete desalination and stirred for 10 minutes at room temperature. Subsequently, the concentration of dissolved anthranilic acid was determined in the aqueous phase. The latter was 17.0 g/L.

3.00 g of dry calcium anthranilate were stirred into 50 ml of complete desalination and stirred for 10 minutes at room temperature. Subsequently, the concentration of dissolved anthranilic acid was determined in the aqueous phase. The latter was 17.5 g/L.

EXAMPLES 4 AND 5 glutamic acid rodlike rods for production of anthranilic acid with initial loading of calcium carbonate Fed-batch fermentation of bacterial species

Growth of a preculture of an anthranilic acid-producing C.glutamicum strain in 25 mL of preculture medium I. The culture was incubated in a 300 mL Erlenmeyer flask at 30 ℃ and 200 rpm for 6 hours in a shaker incubator with a shaking diameter of 5 cm.

Subsequently, 20 mL of the culture was distributed on 2X 50 mL of preculture medium II and incubated for 5 hours at 30 ℃ and 200 rpm in a shaker incubator with a shaking diameter of 5 cm.

After the incubation time of the secondary preculture was over, 40 mL of the secondary preculture was transferred to the growth fermenter. The growth fermenter was initially charged with a starting volume of 0.76L of growth medium, with the amount of all media components except glucose being expected for a volume of 1.00L. The amount of glucose added was chosen so that a concentration of 40 g/L was present in a volume of 0.80L (the initial loading volume including the volume of the preculture). The growth fermenter was operated in fed-batch operation at a cultivation temperature of 30 ℃ in the range of 5.0 to 50 g/L glucose by adding a glucose-tryptophan stock solution. The pH value was kept constant during the cultivation by adding an ammonia base. The fermenter was bubbled with 0.2L/min of air, wherein the dissolved oxygen was adjusted to 30% air saturation by adjusting the stirrer revolutions between 200 and 1200 revolutions/min. The growth fermenter was run in fed-batch operation for a 24 hour incubation time.

After the end of the culture time for the growth fermenter, 50 mL of culture was transferred to the main culture fermenter to establish the starting OD₆₀₀= 20. Inoculating four main culture fermentors, two of which are CaCO-free₃Run with two fermentors containing an additional 20 g/L CaCO in the medium (example 4-comparative)₃Run (example 5-step (I) of the invention). Without addition of CaCO₃The results of (a) are shown in fig. 2. In addition, CaCO is added₃The results of the reactor of (a) are shown in figure 3. Each fermenter was initially charged with a starting volume of 0.55L of main medium I, which includes CaCO in addition to glucose₃The amount of all media components inside is expected for a volume of 1.00L. The amount of glucose added was chosen so that there was a concentration of 40 g/L in a volume of 0.60L (the initial loading volume including inoculum). The main culture fermentor was run in fed-batch operation at a culture temperature of 30 ℃ in the range of 5.0 to 50 g/L glucose by adding a glucose stock solution. The pH was kept constant at pH = 7.0 during the culture by adding ammonia base. The fermenter was bubbled with 0.2L/min of air, wherein the dissolved oxygen was adjusted to 30% air saturation by adjusting the stirrer revolutions between 200 and 1200 revolutions/min. The main culture fermenter was run in fed-batch operation for a cultivation time of 50 hours. Figures the dry biomass, the amount of anthranilic acid (oAB) produced and the course of glucose consumed during fermentation shown in figures 2 and 3 of the accompanying drawings indicate CaCO in solid form₃Has a positive effect on the amount of oAB produced and the amount of glucose converted. The dry weight shown in FIG. 3 comprises CaCO₃Solids and dried biomass; the starting value of the dry weight is thus compared to the CaCO-free value in FIG. 2₃The reactor for solids is significantly higher.

EXAMPLE 6 Corynebacterium glutamicum production of anthranilic acid with initial loading of calcium carbonateBacteria Fed-batch fermentation of seeds

Growth of a preculture of an anthranilic acid-producing C.glutamicum strain in 25 mL of preculture medium I. The culture was incubated in a 300 mL Erlenmeyer flask at 30 ℃ and 200 rpm for 6 hours in a shaker incubator with a shaking diameter of 5 cm.

Subsequently, 20 mL of the culture was distributed on 2X 50 mL of preculture medium II and incubated for 5 hours at 30 ℃ and 200 rpm in a shaker incubator with a shaking diameter of 5 cm.

After the end of the cultivation time of the secondary preculture, 50 mL of the secondary preculture were transferred directly into the main cultivation fermenter. Two main culture fermentors were run. The two main culture fermenters were each initially loaded with a starting volume of 0.55L of main medium II, wherein the amount of all medium components except glucose was expected for a volume of 1.00L. The amount of glucose added was chosen so that there was a concentration of 40 g/L in a volume of 0.60L (the initial loading volume including the volume of the preculture). The main culture fermentor was run in fed-batch operation at a culture temperature of 30 ℃ in the range of 5.0 to 50 g/L glucose by adding a glucose stock solution. The fermentation results are shown in fig. 4 and 5. To reduce the initial pH to a value below 8.6, CO in the air was fed during the first 15 hours of fermentation₂The content was adjusted to 5 vol%. After a fermentation time of 15 hours, the bubbling in both fermenters was switched to air and maintained during the further progress of the fermentation. By adding an ammonia base, the pH is prevented from dropping to a value below 6.8 after 48 hours. The addition of ammonia base was discontinued after a fermentation time of 68 hours to further lower the pH. The fermenter was bubbled with an oxygen-containing gas mixture at a volume flow of 0.2L/min, wherein the dissolved oxygen was adjusted to 30% air saturation by adjusting the stirrer revolutions between 200 and 1200 revolutions per minute. The progress of the dry biomass, the amount of anthranilic acid (oAB) produced, and the glucose consumed during fermentation shown in figure 4 indicates CaCO in solid form₃Has a positive effect on the amount of oAB produced and the amount of glucose converted. Drawing (A)4 contains CaCO in the dry weight₃Solids and dried biomass; the starting value of the dry weight is thus compared to the CaCO-free value in FIG. 2₃The reactor for solids is significantly higher. By lowering the pH shown in FIG. 5 to a pH of 6.8, CaCO was accelerated₃Dissolving. Without CaCO as in FIG. 2₃Reactor phase comparison of solids by CaCO₃The buffering action of (a) can reduce the amount of base required by about 50%.

Example 7 model for precipitation of anthranilic acid from aqueous ammonium anthranilate solution (see FIG. 6)

The model was written in the AspenPlus process simulation tool. The main components considered are water, anthranilic acid, ammonia and CO₂. The thermodynamic model on which this is based takes into account equilibrium reactions, such as formation of bicarbonate, dissociation reactions and formation of salts or solid anthranilic acids. The equilibrium constants and henry constants are from existing databases. In this model, a simple Flash calculation is performed, with the steam content set equal to 0. The established pressure, the pH value and the proportion of anthranilic acid present in solid form are therefore calculated in particular. As shown in FIG. 6, it can be shown by means of this model that at a pressure of 100 bar, the CO is used₂From an aqueous solution of ammonium anthranilate (mass ratio w)_oAB= 0.3) 65.8% anthranilic acid crystallized.

Example 8 precipitation of anthranilic acid from aqueous ammonium anthranilate solution (see FIG. 7)

By injecting CO in a temperature-controlled phase equilibrium cell₂Whereas equimolar aqueous solutions of anthranilic acid having anthranilic acid concentrations of 10 mass%, 20 mass% and 30 mass% were placed under pressure so that the pH value in the liquid phase was lowered by the carbonic acid formed. CO production by means of a temperature-controlled screw press₂Specific addition of (a). The pH shift resulted in precipitation of solid anthranilic acid. At various pressure levels up to 60 bar, samples of the liquid phase were taken and analyzed to determine the concentration of anthranilic acid in the liquid phase. The mass balance was then used to calculate the precipitation ratio of anthranilic acid. Results tableIt is clear that a significant proportion (more than 50% of the anthranilic acid present in the solution) can be crystallized from this aqueous solution at pressures of up to 60 bar. By removing the liquid phase, separation of the solid from the liquid phase is subsequently achieved. By this procedure, anthranilic acid can be isolated in solid form. FIG. 7 shows the experimentally determined ratio of precipitated anthranilic acid vs. CO₂And (4) pressure.