Crystalline particles of salts of glutamic acid N,N-diacetic acid

Abstract

The invention relates to a salt of glutamic acid-N,N-diacetic acid (GLDA) of the formula GLDA-Y.sub.mH.sub.n, wherein m is equal to or more than 0.5 and lower than or equal to 2.5, n+m=4, and wherein Y is a monovalent cation that is not a proton, comprising L-GLDA-Y.sub.mH.sub.n to D-GLDA-Y.sub.mH.sub.n in a range between 100:0 and 50:50 (L:D), characterized in that the salt is crystalline, a process to make such crystalline salt, and to uses of such salt, such as, in particular, in detergent compositions.

Claims

1. Salt of glutamic acid-N,N-diacetic acid (GLDA) of the formula GLDA-Y.sub.mH.sub.n, wherein m is equal to or more than 0.5 and lower than or equal to 2.5, n+m=4, and wherein Y is a monovalent cation that is not a proton, comprising L-GLDA-Y.sub.mH.sub.n to D-GLDA-Y.sub.mH.sub.n in a range between 100:0 and 50:50 (L:D), characterized in that the salt is crystalline.

2. Salt of the formula GLDA-Y.sub.mH.sub.n according to claim 1, wherein Y is an alkali metal.

3. Salt of the formula GLDA-Y.sub.mH.sub.n according to claim 1, wherein m is about 1 and n is about 3.

4. Salt of the formula GLDA-Y.sub.mH.sub.n according to claim 1, wherein the salt comprises L-GLDA-Y.sub.mH.sub.n: D-GLDA-Y.sub.mH.sub.n between 75:25 and 50:50 (L:D).

5. Process to prepare the salt of the formula GLDA-Y.sub.mH.sub.n according to claim 1, comprising: a first step providing an aqueous solution containing a salt of GLDA and/or GLDA-H.sub.4, a second step ensuring that the pH of the aqueous solution is equal to or more than 1.8 and less than 5 and performing a racemization step to at least partially racemize the salt of GLDA, one step after the other in random order or simultaneously, and a third step allowing the aqueous solution to crystallize.

6. Process according to claim 5, wherein the pH of the second step is in the range between 1.8 and 4.8.

7. Process according to claim 5, wherein the second step includes a concentrating step.

8. Process according to claim 7, wherein the concentrating step is carried out until the solution has a concentration of equal to or more than 15 wt % up to or equal to 80 wt %, of GLDA-Y.sub.mH.sub.n based on the weight of the aqueous solution.

9. Process according to claim 5, wherein the third step comprises crystallization accomplished by a step selected from the group consisting of allowing the solution to stand until the solution crystallizes, cooling, and seeding.

10. Process according to claim 5, wherein the third step comprises spraying the aqueous solution of the second step on seeding crystals.

11. Process according to claim 5, wherein the third step is performed at a temperature of equal to or below 30° C.

12. Process according to claim 5, wherein the process is a continuous process.

13. Process according to claim 5, comprising an additional step wherein carbonates, silicates, or a combination of carbonates and silicates are added to the resulting product of the third step, so that the pH of an aqueous solution of the resulting product is above 6.

14. Detergent compositions containing the salt of the formula GLDA-Y.sub.mH.sub.n according to claim 1, and further comprising at least one component selected from the group consisting of cleaning additives, antiscaling additives, builders, protective colloids, chelating agents, surfactants, corrosion inhibitors, and inorganic or organic acids.

15. Pharmaceutical preparations containing the salt of the formula GLDA-Y.sub.mH.sub.n according to claim 1, and further comprising a pharmaceutically acceptable carrier.

Description

EXAMPLES

(1) The materials used are:

(2) Dissolvine GL-47-S (a 47 wt % solution of L-GLDA tetrasodium salt in water), ex Akzo Nobel Functional Chemicals LLC, Chicago Ill., USA.

(3) Potassium Hydroxide, 45% Solution, AR®, ex Avantor.

(4) Sodium Hydroxide, 50% Solution, AR®, ex Avantor

(5) XRD Method and Equipment Used for Analysis:

(6) The diffractograms of crystalline salts of GLDA according to this invention were recorded using a Bruker-AXS D8 reflection-diffractometer using Ni filtered Cu—K.sub.α radiation. Generator settings are 40 kV, 40 mA. A graphite monochromator was used with divergence and anti-scatter slit V20 (variable 20 mm), detector slit 0.6 mm. The measuring range was 2Θ=2.0−70.0°, step size 0.02°, time per step 6.5 seconds.

(7) The Topas software package from Bruker was used for the diffractograms.

(8) NMR in this document is .sup.1H NMR.

(9) CZE stands for Capillary Zone Electrophorese

Example 1

Acidification of GLDA Solutions

(10) To lower the pH of a GLDA-Na.sub.4 solution, Dissolvine GL-47-S, an acidification was performed using a Bi-Polar Membranes (BPM) process. In the BPM process, a bipolar membrane electrodialysis stack was used as described in WO 2008/065109. Such a unit consists of bipolar membranes and a cation exchange membrane. The sodium cations are removed through the cationic exchange membrane, while the hydrogen is added into the product stream via an electrochemical reaction. That way the solution is gradually acidified without having residual sodium cations present. This means that a “salt-free” acidification has occurred.

(11) The experimental set-up consisted of three vessels to recycle fluids through the BPM unit. The temperature was controlled by applying heating/cooling to the jacketed reactors. The acid reactor was a 1 I stirred glass reactor and the base and electrolyte loop both used 1.5 I glass reactors without stirring. Nitrogen was passed through the electrolyte solution via a gas sparger in order to dilute the hydrogen gas produced at the cathode to far below the explosion limit.

(12) The reactor was charged with a ca 42 wt % GLDA-Na.sub.4 solution and the recirculation of the reactor content over the BPM stack was started. Once the GLDA-solution was heated to 40° C., an electric current was applied. The voltage (V) over the stack was limited to 25V and the electric current (I) was controlled manually to a maximum of 15 A. When the desired pH was reached, the current to the BPM was minimized and both the reactor and BPM contents were collected.

(13) The acidified GLDA solution was established to be a 44 wt % solution of GLDA having a pH of about 2.5.

Example 2

Preparation of Crystalline D,L-GLDA-NaH3

(14) The resulting 44.1 wt % L-GLDA aqueous solution with pH 2.5 (which corresponds to a solution containing about 1 equivalent of sodium cation per GLDA anion) of Example 1 were submitted to a heat treatment for 174 hours at approx. 100° C. to provide for racemization. The obtained D,L-GLDA-NaH.sub.3 solution was concentrated to a 50.2 wt % (50:50) L,D-GLDA-NaH.sub.3 aqueous solution in a rotavapor, water bath temperature 70° C. and reduced pressure (20 mbar).

(15) An amount of 1,852 g of the above solution was charged to a 3 I jacketed glass reactor provided with an anchor stirrer. The aqueous solution was heated to 98° C. for full dissolution. Whilst being stirred the clear solution was seeded with GLDA-NaH.sub.3 crystals and cooled to 30° C. within 15 hours.

(16) The crystal slurry was centrifuged in a horizontal Rousselet drum centrifuge to separate the mother liquor from the crystalline product.

(17) After separation, 1,198 g of mother liquor with a concentration of 29.3% (established by way of Fe-TSV, Iron Total Sequestering Value) and 598.6 g of wet cake were obtained. The wet cake was washed twice with a small amount of water and dried under vacuum at 40° C., yielding ˜450 g of dry crystals.

(18) FIG. 2 shows an XRD of the obtained crystals showing interference, fulfilling the Bragg equation.

Example 3

Preparation of D,L-GLDA-KH3

(19) 3 I of Dissolvine GL-47-S aqueous solution were acidified to obtain a 44 wt % solution of GLDA with a pH of 1.25 using the above-described BPM process but running it longer than in Example 1.

(20) 870 g of the 44 wt % L-GLDA aqueous solution with pH 1.25, which is a saturated solution at room temperature, were heated to 80° C. in a glass container until supersaturation. The aqueous solution was allowed to stand in the container for 63 days at 80° C. in an oven, allowing the concentrated aqueous solution to racemize and to crystallize. The precipitate in the mother liquor was ground and the obtained slurry was filtered applying a G3 glass filter. The wet cake was subsequently washed with ice water and dried under vacuum at ambient temperature. After drying 191.3 g of D,L-GLDA-H.sub.4-crystals were obtained.

(21) 78.0 g of the D,L-GLDA-H.sub.4 crystals were dispersed in 62 g demineralized water.

(22) To the stirred slurry 37 g of KOH-45% aqueous solution were added, dissolving the crystals and reaching a pH of 2.34 as is.

(23) To the obtained slightly turbid solution further KOH-45% aqueous solution was added to obtain a pH of 2.50 (as 1% in water). The solution was filtered using a syringe with 0.45 μm filter.

(24) The clear solution was heated to 95° C. and allowed to cool to 50° C. and stirred overnight.

(25) The obtained white precipitate was isolated applying a G3 glass filter. The wet cake was washed twice with a small amount of cold water and dried under vacuum at 25° C.

(26) FIG. 3 shows an XRD of the obtained crystals showing interference, fulfilling the Bragg equation.

Example 4

Test of Hygroscopicity

(27) GLDA-NaH.sub.3 crystals

(28) Dissolvine GL-47-S was acidified in a two-step process by way of ion exchange using first the ion exchange resin Duolite C-476, Rohm&Haas, 3,000 liters, and next the ion exchange resin Lewatit CNP-80, Bayer, 5,500 liters. The aqueous GLDA-NaH.sub.3 solution obtained (pH 3.2 as is) was concentrated under atmospheric pressure within approx. 12 hours at an initial boiling temperature of approx. 105° C., a temperature that became 115° C. at increasing concentration.

(29) A 40 L-reactor was pre-charged with 29.5 kg of the obtained 40.4 wt % solution having a pH of 3.2 as is.

(30) The reactor content was stirred for 14 hours at 100° C. and concentrated to give a 60.4 wt % D,L-GLDA-NaH.sub.3 solution.

(31) The aqueous GLDA-NaH.sub.3 solution was allowed to cool to 40° C. and kept at this temperature for 24 hours to allow the D,L-GLDA-NaH.sub.3 to crystallize.

(32) 18.99 kg of the resulting slurry were filtered applying a G3 glass filter, yielding 7.34 kg of wet cake and 11.65 kg of mother liquor (Fe-TSV=55.9%).

(33) The wet cake was subsequently dried at 40° C. under vacuum and milled, yielding a crystalline GLDA-NaH.sub.3 powder. The crystalline powder was compared with amorphous product in a moisture absorption test.

(34) Amorphous GLDA-NaH.sub.3

(35) Dissolvine GL-47-S was acidified to a pH of 3.0 using the above-described BPM process.

(36) The solution was spray-dried applying a NIRO A/S MOBILE MINOR.sup.tm spray dryer at an inlet temperature of 220° C., an outlet temperature of 115° C., and a spray pressure nozzle (gap=1 mm) of 1 bar.

(37) The hygroscopic properties of the obtained amorphous GLDA-NaH.sub.3 powder were compared to the GLDA-NaH.sub.3 crystals using a moisture absorption test.

(38) 3.498 g GLDA-NaH.sub.3 crystals and 6.114 g spray-dried (amorphous) GLDA-NaH.sub.3 were weighed in. Both solids were stored at 16° C. and 60% Relative Humidity.

(39) After 52 hours the weight was found to be 3.509 g for the crystalline GLDA-NaH.sub.3 and 6.871 g for the amorphous GLDA-NaH.sub.3.

(40) The spray dried, amorphous GLDA-NaH.sub.3 showed a weight increase of more than ˜12 wt %. The crystalline GLDA-NaH.sub.3 had a weight increase of only 0.3 wt % and remained stable (no further moisture pick-up).

(41) The comparison between the moisture uptake of amorphous GLDA-NaH.sub.3 and the crystalline GLDA-NaH.sub.3 as a function of time is shown in FIG. 4. This shows that the crystalline product has significantly reduced hygroscopic properties.

Example 5

Preparation of Crystalline D L-GLDA-NaH with Temperature and Pressure Treatment Step

(42) The resulting 44.1 wt % L-GLDA aqueous solution with pH 2.5 (which corresponds to a solution containing about 1 equivalent of sodium cation per GLDA anion) of Example 1 was submitted to a heat and pressure treatment by precharging a 2 L-ss jacketed autoclave provided with a Ruston turbine stirrer with 1.5 I of L-GLDA-NaH.sub.3-solution. After inertization of the system with N2-gas, the solution was heated to 135° C. Whilst stirring the temperature was maintained at 135° C., meanwhile the pressure was increased from 2.5 to 2.7 barg. After 3 hours, it was established by monitoring the optical rotation that conversion to a full racemic mixture was completed. After cooling to 70° C. the D,L-GLDA-NaH.sub.3 solution was collected in a container.

(43) The obtained D,L-GLDA-NaH.sub.3 solution was concentrated to a 50 wt % (50:50) L,D-GLDA-NaH.sub.3 aqueous solution in a rotavapor, water bath temperature 70° C. and reduced pressure (20 mbar).

(44) The concentrated solution was charged to a 3 I jacketed glass reactor provided with an anchor stirrer. The aqueous solution was heated to 98° C. for full dissolution. Whilst stirring the clear solution was seeded with GLDA-NaH.sub.3 crystals and cooled to 30° C. within 15 hours.

(45) The crystal slurry was centrifuged in a horizontal Rousselet drum centrifuge to separate the mother liquor from the solid product.

(46) After separating off the mother liquor, the wet cake was washed, dried under vacuum at 40° C., yielding dry material that was established to be crystalline by XRD.

Comparative Example 6

Reworking EP-0591934 A1-Example 2

(47) Preparation of GLDA-Na.sub.4

(48) The reactor was charged with 80.0 g monosodium glutamate (ex Ajinomoto), 400 g demineralized water, and 36.0 g NaHCO.sub.3 (ex J.T.Baker). A solution of 104 g monochloro acetic acid (MCA) dissolved in 400 ml demineralized water was cautiously neutralized with 92.4 g NaHCO.sub.3. Whilst stirring the MCA sodium solution was combined with the reactor content. The reaction mixture was heated to 74° C. The pH was kept between 9 and 10 by dosing 30 wt % aqueous NaOH. After dosing of 192 g of 30% aqueous NaOH a pH of 9.8 was reached and the reaction mixture was stirred for another hour.

(49) The reaction mixture was analyzed for impurities by Capillary Zone Electrophoresis. The level of impurities was reasonably low (see Table 1 below).

(50) Whilst cooling the reactor content in a water bath of 15° C. concentrated H.sub.2SO.sub.4 solution was dosed until the pH was 2 as is (pH 1% sol. 2.5). During dosing of sulfuric acid to the reaction mixture strong CO.sub.2 gas evolution was observed (CO.sub.2 results from the carbonate).

(51) In total 1,340 g of mixture were collected with Fe-TSV of 6.76 wt % expressed as GLDA-NaH.sub.3). On the basis of the pH it was concluded that the product contains about one equivalent of sodium per GLDA and is actually the monosodium salt of GLDA. For simplicity's sake it is referred to in the remainder as GLDA-NaH.sub.3 or simply as GLDA.

(52) The yield based on mono sodium glutamate intake was 80.6% GLDA-NaH.sub.3.

(53) TABLE-US-00001 TABLE 1 Composition of the GLDA-Na.sub.4 solution Component Wt % IDA-Na.sub.2 <0.05 HO—CH.sub.2—COONa 1.4 GLMA 2 HCOONa 0.1 GLDA-Na.sub.4 8.3
Solidification of the GLDA-NaH.sub.3

(54) The acidified reaction mixture was split into two parts. One part was stored at ambient temperature. The other part (670 g) was concentrated in vacuo until half the volume was reached and this solution was allowed to crystallize and analyzed by CZE (see Table 2 below). The filtrate was concentrated further until a paste remained. A small amount of acetone was added to the paste and the sample was stored in the refrigerator at 4° C. for a month. After this time the appearance of the sample looked unchanged. The acetone was removed by decanting. After drying the residue in a vacuum oven at 85° C., the product increased in volume and transformed to a foam-like solid. The material was milled applying a blender before being analyzed by NMR, XRD, CZE, HPLC, and titration with FeCl.sub.3 on TSV. The Fe-TSV was determined to be 17.9 wt % expressed as GLDA-H.sub.4. By the HPLC analysis the GLDA-NaH.sub.3 content was determined to be 15.8±1.5%.

(55) TABLE-US-00002 TABLE 2 CZE analysis of composition of solution allowed to crystallize Component Wt % GLDA-NaH.sub.3 12.4 IDA-H.sub.2 <0.1 Glycolic acid 2.2 GLMA 3.2 Formic Acid 0.2 Na.sub.2SO.sub.4 24.0 NaCl 8.4 % GLDA on total 69 organic fraction GLDA:inorganic salt ~1:2.6

(56) To prove the presence of GLDA-NaH.sub.3 in the dry solid the product was analyzed by NMR and it was confirmed that the sample still contained a lot of salt and other organic material, as indicated in Table 3 below.

(57) TABLE-US-00003 TABLE 3 Chemical composition of organics by NMR of the obtained solid Compound Wt % GLDA-NaH.sub.3 13.8 GLMA 7.35 Glycolic acid 0.10

(58) Finally, the solid material was submitted to XRD analysis. Also a XRD diffractogram was taken of D,L-GLDA-NaH.sub.3 (as prepared in above Examples 2 and 5). Comparing the diffractograms it must be concluded that the sample does not contain crystalline GLDA. It can be established that the main component in the product is NaCl with a crystallinity of 37%.

(59) Reworking patent EP591934A1—Synthesis Example 2 showed that it is possible to prepare GLDA solution with 74.4% yield based on mono sodium glutamate intake. However, after the addition of the sulfuric acid it was no longer possible to work analogous to the procedure described in the patent. For example, no white powder was formed. Analysis of the products that were obtained demonstrated there was no formation of crystals of GLDA sodium salt. This confirms that sodium GLDA will only crystallize after a racemization step that causes the compound to at least partially racemize. Also, the high amount of salt will have had an inhibiting influence on the crystallization of the organic GLDA material.