Crystalline particles of glutamic acid N,N-diacetic acid

Abstract

The invention relates to glutamic acid N,N-diacetic acid (GLDA) of the formula GLDA-Y.sub.mH.sub.n, wherein m is less than 0.5, n+m=4, Y is a monovalent cation that is not a proton, in the form of crystals, a process to make these crystals, and their uses, in particular in detergent compositions.

Claims

1. Glutamic acid N,N-diacetic acid (GLDA) of the formula GLDA-Y.sub.mH.sub.n, wherein m is less than 0.5, n+m=4, Y is a monovalent cation that is not a proton, in the form of crystals.

2. GLDA-Y.sub.mH.sub.n according to claim 1, wherein m is about 0.

3. GLDA-Y.sub.mH.sub.n according to claim 1, wherein the GLDA-Y.sub.mH.sub.n comprises L-GLDA-Y.sub.mH.sub.n to D-GLDA-Y.sub.mH.sub.n in a range of from 100:0 to 50:50 (L:D).

4. Process to prepare glutamic acid N,N-diacetic acid (GLDA) of the formula GLDA-Y.sub.mH.sub.n, wherein m is less than 0.5, n+m=4, Y is a monovalent cation that is not a proton, in the form of crystals, the process, comprising: a first step of providing an aqueous solution of GLDA or a salt thereof, a second step of ensuring that the pH of the aqueous solution is below 1.8, and a third step of allowing the aqueous solution to crystallize, wherein the aqueous solution that is allowed to crystallize contains at least 15 wt % of GLDA-Y.sub.mH.sub.n on total solution.

5. Process according to claim 4, wherein the pH of the second step is in the range of between 1.0 and 1.7.

6. Process according to claim 4, wherein the second step includes a concentrating step that is carried out until the solution has a concentration of equal to or more than 15 wt % to up to or equal to 80 wt %, of GLDA-Y.sub.mH.sub.n based on the weight of the aqueous solution.

7. Process according to claim 4, wherein the aqueous solution that is allowed to crystallize in the third step contains at least 75 wt % of GLDA-Y.sub.mH.sub.n based on the total organic compounds.

8. Process according to claim 4, wherein the second step comprises a racemization step.

9. Process according to claim 4, wherein the third step comprises crystallization accomplished by one or more steps selected from the group consisting of allowing the solution to stand until the solution crystallizes, cooling, and seeding.

10. Process according to claim 4, wherein the third step comprises spraying the aqueous solution of the second step on seeding crystals.

11. Process according to claim 4, wherein the third step is performed at a temperature of equal to or below 30° C.

12. Process according to claim 4, wherein the process is a continuous process.

13. Detergent compositions containing glutamic acid N,N-diacetic acid (GLDA) of the formula GLDA-Y.sub.mH.sub.n, wherein m is less than 0.5, n+m=4, Y is a monovalent cation that is not a proton, in the form of crystals, and further comprising at least one component selected from the group consisting of cleaning additives, silicates, carbonates, bicarbonates, antiscaling additives, builders, protective colloids, chelating agents, surfactants, inorganic acids, organic acids, and corrosion inhibitors.

14. Pharmaceutical preparations containing glutamic acid N,N-diacetic acid (GLDA) of the formula GLDA-Y.sub.mH.sub.n, wherein m is less than 0.5, n+m=4, Y is a monovalent cation that is not a proton, in the form of crystals, and further comprising a pharmaceutically acceptable carrier.

15. Process according to claim 4 wherein the aqueous solution that is allowed to crystallize in the third step contains GLDA-Y.sub.mH.sub.n in a weight ratio of GLDA-Y.sub.mH.sub.n:inorganic compounds of higher than 1:1.

16. Process according to claim 7 wherein the aqueous solution that is allowed to crystallize in the third step contains GLDA-Y.sub.mH.sub.n in a weight ratio of GLDA-Y.sub.mH.sub.n:inorganic compounds of higher than 1:1.

Description

EXAMPLES

(1) The materials used are:

(2) Dissolvine GL-47-S (a 47 wt % solution of L-GLDA-Na.sub.4 tetrasodium salt in water), ex Akzo Nobel Functional Chemicals LLC, Chicago Ill., USA.

(3) XRD Method and Equipment Used for Analysis

(4) The diffractograms of crystalline 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.

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

(6) NMR in this document means .sup.1H NMR.

(7) CZE stands for Capillary Zone Electrophorese.

Example 1 Acidification of GLDA Solutions

(8) To produce the GLDA-H.sub.4 solution, the pH of a GLDA-Na.sub.4 Dissolvine GL-47-S solution was lowered to about 1.2, 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.

(9) 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 l stirred glass reactor and the base and electrolyte loop both used 1.5 l 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.

(10) The reactor was charged with a ca 40 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. The acidified GLDA solution was established to be a 44 wt % L-GLDA solution with a pH of about 1.2 as is.

Example 2 Preparation of D,L-GLDA-H4

(11) 870 g of 44 wt % L-GLDA-H.sub.4 aqueous solution prepared in accordance with Example 1, which means a saturated solution, were heated to 80° C. in a glass container until supersaturation was reached. The aqueous solution was allowed to stand in a well-closed container for 63 days at 80° C. in an oven, allowing the concentrated aqueous solution to crystallize.

(12) The precipitate in the mother liquor was ground and the obtained slurry was filtered applying a G3 glass filter.

(13) The wet cake was subsequently washed twice with a small amount of ice water and dried under vacuum at ambient temperature. After drying 152.3 g GLDA-H.sub.4-crystals were obtained (first crop).

(14) The warm mother liquor was allowed to cool to ambient temperature within 20 minutes.

(15) During cooling the mother liquor showed fast crystallization.

(16) Evaluation of the slurry applying an optical microscope displayed hexagonal crystals and agglomerates.

(17) The obtained slurry was filtered applying a G3 glass filter and the remaining wet cake was washed twice with a small amount of ice water.

(18) The wet cake was dried under vacuum at ambient temperature, yielding a second crop of 102.7 g dry crystals at assay Fe-TSV=92.7%. Optical rotation=0°.

(19) An XRD was taken of crystals from the second crop.

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

Example 3 Preparation of L-GLDA-H4

(21) 3 l of Dissolvine GL-47-S aqueous solution were acidified to a pH of 1.2 as is, using BPM.

(22) The resulting 44 wt % L-GLDA-H.sub.4 aqueous solution was concentrated to a 50 wt % L-GLDA-H.sub.4 aqueous solution using a rotavapor, water bath temperature 30° C., and reduced pressure (20 mbar).

(23) 2,500 g of the resulting solution were pre-charged into a 3 l jacketed glass reactor provided with an anchor stirrer.

(24) The aqueous solution was maintained at ambient temperature, the clear solution was seeded with 5.3 g L-GLDA-H.sub.4 crystals with stirring and stirred overnight.

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

(26) After separation, 1,992 g of mother liquor with a concentration of 42.7% (established by way of Fe-TSV, Iron Total Sequestering Value) and 800.0 g of wet cake were obtained. The wet cake was dried under vacuum at 45° C. yielding 612 g of dry material established to be L-GLDA-H.sub.4 crystals by XRD.

Example 4 Hygroscopicity Tests on GLDA Acid

(27) 10.016 g of the D,L-GLDA-H.sub.4 crystals prepared in Example 2 were compared to amorphous GLDA-H.sub.4 with regard to their hygroscopicity.

(28) Dissolvine GL-47-S was acidified to a pH of 1.2 in accordance with Example 1.

(29) The aqueous GLDA solution was spray-dried applying a NIRO A/S MOBILE MINOR™ 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.

(30) The hygroscopic properties of the obtained amorphous powder were compared to the crystals using a moisture absorption test.

(31) 10.016 g GLDA-H.sub.4 crystals and 10.000 g spray-dried (amorphous) GLDA-H.sub.4 were weighed in. Both solids were stored at 16° C. and 60% Relative Humidity.

(32) After 48.5 hrs the weight was found to be 10.116 g for the crystalline GLDA-H.sub.4 and 10.807 g for the amorphous GLDA-H.sub.4. The spray-dried, amorphous GLDA-H.sub.4 showed a weight increase of more than ˜8 wt %. The crystalline GLDA-H.sub.4 had a weight increase of only 1 wt %

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

Comparative Example 5—Reworking EP0884381A1—Synthesis Example 1

(34) The reactor was charged with 662.1 g Glutamic acid (ex Fluka), 738 g 40% NaOH (ex J. T. Baker) and 422 g demineralized water. Whilst stirring the reactor content was heated to 90° C. 233 g HCN, 855 g 30% formaldehyde (ex Fluka), and another 738 g 40% NaOH were dosed simultaneously within 2 hours. The resulting mixture was stirred at 105° C. for 2 hrs. The remaining cyanide was reduced to 47 ppm by the addition of 8 g 30% formaldehyde. The reaction mixture (3,490 grams) was cooled down to ambient temperature and was analyzed by titration on Fe—Total Sequestering Value being 20.1 wt % expressed as GLDA-Na.sub.4.

(35) This reaction mixture was analyzed by Capillary Zone Electrophorese (CZE) and the analytical data (Table 1) displayed that the sample still contained ˜26 wt % of the precursor I-GLMA (i.e. linear glutamic acid monoacetic acid, also a cyclized version of this compound exists). The presence of such an amount of GLMA actually shows a very bad conversion to GLDA.

(36) TABLE-US-00001 TABLE 1 Composition of reaction mixture Component Wt % IDA-Na.sub.2 1.4 HO—CH.sub.2—COONa 1 GLMA 26 NTA-Na.sub.3 3.5 HCOONa 0.34 GLDA-Na.sub.4 15.2
Preparation of the GLDA-H.sub.4

(37) To a 1 L-glass reactor provided with a 4-blade stirrer 543 g of the above reaction mixture were charged. Whilst stirring 333 g of 40% H.sub.2SO.sub.4 (ex J. T. Baker) were added. The pH of the reaction mixture became 1.8 (as is) at a temperature of 33° C. A sample of the aqueous liquid was analyzed by CZE (see Table 2). Because no crystallization was observed, the reaction mixture was seeded with a spatula tip of L-GLDA-H.sub.4 crystals; however, these dissolved within 20 minutes. After the reactor content was cooled to ambient temperature additional seeds were added.

(38) TABLE-US-00002 TABLE 2 Composition of aqueous solution that was allowed to crystallize Component Wt % IDA acid 1.1 Glycolic acid 0.8 GLMA acid 19.5 NTA-H.sub.3 2.6 Formic acid 0.2 Na.sub.2SO.sub.4 30.0 GLDA-H.sub.4 9.5 % GLDA on total 28.1 organic fraction GLDA:inorganic ~1:3 material

(39) After 11 days of stirring the reactor content was turned into white slurry. Microscopic determination showed large needle-shaped crystals. Besides the big crystals also very tiny, probably amorphous, particles were seen. The slurry was filtered applying a G2 glass filter, with 402 g wetcake being obtained. The Fe-TSV value was established to be about 4 wt % expressed as GLDA-H4. The mother liquor, being 343 grams, had a Fe-TSV of about 16% expressed as GLDA-H4. The wetcake was filtered off, dried, and analyzed by NMR (see Table 3 below) and XRD. Only 4 wt % was established to be organic material.

(40) TABLE-US-00003 TABLE 3 Chemical composition of organics by NMR of the wetcake (~96% Na.sub.2SO.sub.4) Component Wt % GLDA-H.sub.4 2.6 GLMA acid 0.6 Glycolic acid 0.5 NTA-H.sub.3 0.4 Sum ~4.0
XRD Determination

(41) XRD and NMR analyses showed that the crystals in the sample were Na.sub.2SO.sub.4. When comparing the XRD diffractogram with a XRD diffractogram of crystalline L-GLDA-H.sub.4 and D, L-GLDA-H.sub.4 (as prepared in above Examples 2 and 3), it can be concluded that the procedure of Example 1 of EP-A-0884381 does not result in crystalline GLDA-H.sub.4 and that the only crystals present in the sample are sulfate salt crystals.

(42) The measured Fe-TSV value of the wetcake must be explained by a remaining small amount of moisture (mother liquor) attached to the salt crystals in the wetcake, as a calculation showed that the GLDA concentration in the reaction mixture and the amount of liquid present in the cake fit with the above explanation.

(43) Reworking the procedure written in patent EP0884381A1—Synthesis Example 1 gave a reaction mixture with a relatively low amount of GLDA and a lot of the precursor GLMA, which indicates a low conversion, i.e. it was not possible to obtain comparable yields to those indicated in EP0884381A1. Most importantly, we did not observe any GLDA crystals in the product. This is primarily because the solution allowed to crystallize contains way too little GLDA. Additionally, the very high salt load and the presence of other organic material are also disturbing a crystallization of GLDA.