PROCESS FOR THE PREPARATION OF A METASTABLE CRYSTAL MODIFICATION OF N-(AMINOIMINOMETHYL)-2-AMINOACETIC ACID (III)

Abstract

The present invention relates to a novel crystal modification of N-(aminoiminomethyl)-2-aminoacetic acid, crystal mixtures, and a process for preparing said crystal modification and said crystal mixtures.

Claims

1. A process for preparing N-(aminoiminomethyl)-2-aminoacetic acid containing N-(aminoiminomethyl)-2-aminoacetic acid in a thermodynamically metastable crystal modification, whereby the thermodynamically metastable crystal modification shows in the X-ray powder diffractogram of the crystal modification when using Cu-Kα radiation the strongest reflection bands at 2Θ=20.2° and 23.3° and 23.8° and 25.3° with a measurement accuracy of +/−0.2°, characterized in that N-(aminoiminomethyl)-2-aminoacetic acid is crystallized from a water-containing solution in the presence of at least one guanidine compound of formula (I), wherein formula (I) represents: ##STR00008## where radicals R′, R.sup.2, R.sup.3, R.sup.4 and X, Y and index k in formula (I) independently of one another mean: R.sup.1, R.sup.2=independently of one another hydrogen, C1 to C4 alkyl or, with the formation of a ring, together a radical of the formula (II), where the formula (II) is ##STR00009## wherein Y=CH.sub.2, O, NH, NCH.sub.3 or a bond, R.sup.3, R.sup.4=independently hydrogen or C1 to C4 alkyl, X=CH.sub.3COO, Cl, Br, NO.sub.3, SO.sub.3(NH.sub.2) or ½ SO.sub.4, k =0 or 1, whereby the guanidine compound of formula (I) is used in an amount of at least 8 percent by weight (based on the total weight of the solution).

2. The process according to claim 1, wherein the water-containing solution contains at least 40% by weight of water (based on the total weight of the solution).

3. The process according to claim 1, wherein N-(aminoiminomethyl)-2-aminoacetic acid is dissolved in water or a water-containing solution in a first process step, and the N-(aminoiminomethyl)-2-aminoacetic acid containing N-(aminoiminomethyl)-2-aminoacetic acid in a thermodynamically metastable crystal modification is crystallized in a second process step from the solution prepared in the first process step in the presence of the guanidine compound of formula (I).

4. The process according to claim 1, wherein N-(aminoiminomethyl)-2-aminoacetic acid is prepared in a first process step from cyanamide and glycine in water or in a water-containing solution, and the N-(aminoiminomethyl)-2-aminoacetic acid containing N-(aminoiminomethyl)-2-aminoacetic acid in a thermodynamically metastable crystal modification is crystallized in a second process step from the reaction mixture prepared in the first process step in the presence of the guanidine compound of formula (I).

5. The process according to claim 1, wherein the thermodynamically metastable crystal modification has the orthorhombic space group P2.sub.12.sub.12.sub.1 with Z=8 with lattice constants a=7.7685 Å, b=7.7683 Å and c=17.4261 Å at 105 Kelvin and a measurement accuracy of +/−0.001 ∈.

6. The process according to claim 1, wherein the guanidine compounds of formula (I) are used in an amount corresponding to 80% of the maximum amount which can be dissolved in water at 25° C. under normal pressure.

7. The process according to claim 1, wherein N-(aminoiminomethyl)-2-aminoacetic acid is dissolved or prepared in the water-containing solution in the first process step at a temperature in the range of 20 to 100° C. at normal pressure.

8. A crystal mixture containing N-(aminoiminomethyl)-2-aminoacetic acid in a thermodynamically metastable crystal modification, whereby the thermodynamically metastable crystal modification shows in the X-ray powder diffractogram of the crystal modification when using Cu-Kα radiation the strongest reflection bands at 2 0=20.2° and 23.3° and 23.8° and 25.3° with a measurement accuracy of +/−0.2°, and N-(aminoiminomethyl)-2-aminoacetic acid in a thermodynamically stable crystal modification.

9. The crystal mixture according to claim 8, wherein the crystal mixture contains N-(aminoiminomethyl)-2-aminoacetic acid in a thermodynamically metastable crystal modification and N-(aminoiminomethyl)-2-aminoacetic acid in a thermodynamically stable crystal modification in a weight ratio in the range from 0.1: 9.9 to 9.9: 0.1.

10. A feed additive for breeding and fattening animals comprising a crystal mixture containing N-(aminoiminomethyl)-2-aminoacetic acid in a thermodynamically metastable crystal modification, whereby the thermodynamically metastable crystal modification shows in the X-ray powder diffractogram of the crystal modification when using Cu-Kα radiation the strongest reflection bands at 2Θ=20.2° and 23.3° and 23.8° and 25.3° with a measurement accuracy of +/−0.2°, and N-(aminoiminomethyl)-2-aminoacetic acid in a thermodynamically stable crystal modification.

11. The feed additive according to claim 10, wherein the crystal mixture contains the N-(aminoiminomethyl)-2-aminoacetic acid in a thermodynamically metastable crystal modification and the N-(aminoiminomethyl)-2-aminoacetic acid in a thermodynamically stable crystal modification in a weight ratio in the range from 0.1: 9.9 to 9.9: 0.1.

Description

DESCRIPTION OF THE DRAWINGS

[0117] The drawings show:

[0118] FIG. 1: X-ray powder diffractogram of N-(aminoiminomethyl)-2-aminoacetic acid of form A of Example 1.

[0119] FIG. 2: X-ray powder diffractogram of N-(aminoiminomethyl)-2-aminoacetic acid of form B of Example 2.1.

[0120] FIG. 3: Photomicrograph of N-(aminoiminomethyl)-2-aminoacetic acid of form A prepared according to Example 1 (image width 8 mm).

[0121] FIG. 4: Photomicrograph of polygonal aggregates of N-(aminoiminomethyl)-2-aminoacetic acid of form B, prepared by recrystallization from a50% water-containing guanidine hydrochloride solution according to Example 2.1 (image width 8 mm).

[0122] FIG. 5: Solubility curve of N-(aminoiminomethyl)-2-aminoacetic acid of form A and form B, respectively, in water.

[0123] FIG. 6: Illustration of the two crystallographically independent molecules N-(aminoiminomethyl)-2-aminoacetic acid from single crystal X-ray structural analysis.

[0124] FIG. 7: Illustration of the packing of the molecules of N-(aminoiminomethyl)-2-aminoacetic acid in the crystal structure. The direction of view is along the a-axis. Independent molecular chains arranged perpendicular to each other and bound by H bridges can be clearly seen parallel to the a- and b-axis. These chains are stacked along the c-axis.

[0125] FIG. 8: Bulk density depending on concentration form B.

[0126] FIG. 9: Calibration curve proportion of crystal form B to crystal form A.

[0127] FIG. 10: DSC N-(aminoiminomethyl)-2-aminoacetic acid form A.

[0128] FIG. 11: DSC N-(aminoiminomethyl)-2-aminoacetic acid form B.

Examples

Guanidine Compounds Used

[0129] Technically available guanidine compounds were purchased commercially:

[0130] Guanidine hydrochloride: Sigma-Aldrich Order No. G4505

[0131] Guanidine sulfamate: TCI Chemicals Order No. G0022

[0132] Guanidine nitrate: Sigma-Aldrich Order No. 234249

[0133] Guanidine acetate: Sigma-Aldrich Order No. 50920

[0134] N,N′-dimethylguanidine hydrochloride: AlzChem AG

[0135] N,N′-dimethylguanidine sulfate: Sigma-Aldrich Order No. 276669

[0136] N,N′-diethylguanidine sulfate: TCI Chemicals Order No. D2035,

[0137] 1-(aminoiminomethyl)-4-methyl-piperazine sulfate: ABCR GmbH, Order No. AB288540

[0138] 4-(aminoiminomethyl)-morpholine acetate: ABCR GmbH, Order No. AB301888

[0139] N-methylguanidine sulfate: TCI Chemicals, Order No. M1691

[0140] N-ethylguanidine sulfate: Sigma-Aldrich, Order No. 275557

X-Ray Powder Diffraction Measurement

[0141] In the scope of the present examples, X-ray powder diffraction measurements were performed using a Bruker D2 Phaser powder diffractometer with theta/2theta geometry, a LYNXEYE detector, Cu-Kα radiation of wavelength 1.5406 Å with an accelerating voltage of 30 kV and an anode current of 10 mA, a nickel filter and an increment of 0.02°. The samples for examination were ground in an agate mortar and pressed onto the sample plate according to the manufacturer's instructions and the surface was smoothed.

Calibration Line for the Radiographic Determination of the Proportion Form A/B

[0142] XRD data were obtained using mechanical mixtures of pure GAA form A and form B samples. The peak heights at 20.7° and 20.2° were used for quantitative evaluation via the peak height. The calibration curve (calibration line) determined from this with a very good correlation coefficient was used for unknown samples to determine the proportion of form A/B (cf. Table 1 and FIG. 9).

TABLE-US-00001 TABLE 1 Calibration curve proportion of crystal form A to crystal form B Weight Weight X-ray X-ray percentage percentage count rate count rate Ratio of Form B Form A Form A Form B count rate (%) (%) (20.7°) (20.2°) B to A + B 0 100 4000 1 0.00025 5 95 3150 150 0.04545 10 90 3500 500 0.12500 20 80 3500 900 0.20455 33 67 3050 1600 0.34409 50 50 2400 2400 0.50000 67 33 1750 3100 0.63918 80 20 950 3250 0.77381 90 10 400 3700 0.90244 95 5 250 4000 0.94118 100 0 1 4100 0.99976

[0143] For the quantitative determination of the ratio of N-(aminoiminomethyl)-2-aminoethanoic acid crystal form B to crystal form A, mechanical mixtures of powdered samples of the respective pure crystal forms were prepared and measured on the X-ray powder diffractometer. The mixing ratios were 100: 0, 95: 5, 90: 10, 80: 20, 67 : 33, 50: 50, 33: 67, 20: 80, 10: 90, 5: 95 and 0: 100. The signal heights (count rates) at 2theta 20.2° (form B) were related to the sum of the signal heights at 2theta 20.7° (form A) and 2theta 20.2° (form B) and a calibration line was determined from this. With a correlation coefficient R.sup.2=0.998, the following linear relationship was found:

[00001]$\mathrm{Weight}\mathrm{percent}\mathrm{form}B=\left(\left(\frac{\mathrm{count}\mathrm{rate}\mathrm{form}B}{\mathrm{count}\mathrm{rate}\mathrm{form}A+\mathrm{count}\mathrm{rate}\mathrm{form}B}\right)-0.0074\right)*102.04$

[0144] This formula was used in the following examples to determine the respective proportions of crystal form A and crystal form B.

Single Crystal X-Ray Structural Analysis

[0145] A suitable crystal was prepared by evaporating a water-containing solution of N-(aminoiminomethyl)-2-aminoacetic acid in the presence of N,N′-guanidinodiacetic acid. The single crystal measurement was carried out at 105 Kelvin on a crystal of dimension 0.02*0.02*0.09 mm using monochromatic Mo-Kα (molybdenum K-alpha) radiation of wavelength 0.71073 Åusing a dual-cycle Bruker D8 Venture TXS diffractometer. Refinement of the X-ray crystal data using 2072 independent reflections was performed by the least square error method up to an R value (F.sub.obs) of 0.0381. The position of NH and OH hydrogen atoms was refined, and that of CH hydrogen atoms was fixed at the calculated position. The result of the X-ray single crystal structure analysis is illustrated in FIGS. 6 and 7. A powder diffractogram back-calculated from the single crystal structure analysis exactly matched the measured powder diffractogram shown in FIG. 2.

Example 1 (Comparison)—Recrystallization of N-(Aminoiminomethyl)-2-Aminoacetic Acid from Water

[0146] 400 g of water was provided at 80° C. and a total of 11.66 g of N-(aminoiminomethyl)-2-aminoacetic acid with a content of 99.0%, present in crystal form A, were dissolved therein spoonwise, the solubility limit being exceeded with the last portion. It was then filtered off at 80° C., the filtrate was mixed with a further 100 g of water and heated to 80° C. A nearly saturated clear solution was formed. By cooling slowly to 20° C. within 4 hours, N-(aminoiminomethyl)-2-aminoacetic acid was crystallized. The precipitated crystals were filtered off and dried at 60° C. in vacuo. 6.51 g of N-(aminoiminomethyl)-2-aminoacetic acid with a content of 99.1% was obtained.

[0147] The product obtained is in the form of fine acicular crystals. The fine acicular crystals were examined microscopically (see FIG. 3). An X-ray powder diffractometric measurement yielded the powder diffractogram shown in FIG. 1, which indicates the well-known crystal form A.

Example 2—Crystallization of N-(Aminoiminomethyl)-2-Aminoacetic Acid from Guanidine Hydrochloride Solutions

[0148] A 50% solution was prepared from 250 g of guanidine hydrochloride and 250 g of water. To 400 g of this solution, N-(aminoiminomethyl)-2-aminoacetic acid of the same composition as in Example 1 was added spoonwise at 80° C. Only at an added amount of 26.37 g the solubility limit was exceeded. The small solid fraction was filtered off at 80° C., the filtrate was added to the remaining 100 g of the 50% solution of guanidine hydrochloride and stirred at 80° C. for 1 hour. A clear, colorless solution was obtained. By slow cooling to 20° C. within 4 hours, N-(aminoiminomethyl)-2-aminoacetic acid was crystallized. The precipitated crystal aggregates were filtered off, washed 3 times with water at 20° C. and dried at 60° C. 15.56 g of N-(aminoiminomethyl)-2-aminoacetic acid with a content of 99.2% was obtained. The amount obtained is thus 2.4 times greater than in Example 1, which is due to the significantly increased solubility of N-(aminoiminomethyl)-2-aminoacetic acid caused by the guanidine hydrochloride solution.

[0149] An analogously recorded powder diffractogram (see FIG. 2) showed the hitherto unknown crystal form B. The polygonal, roundish crystal aggregates were examined microscopically (see FIG. 4).

[0150] The experiment was repeated in an analogous manner with different concentrations of guanidine hydrochloride in water. It was found that N-(aminoiminomethyl)-2-aminoacetic acid of form A was increasingly formed with decreasing concentration (cf. Table 2). The concentration of the employed guanidine compound in the solvent used for the recrystallization of N-(aminoiminomethyl)-2-aminoacetic acid is therefore of decisive importance.

TABLE-US-00002 TABLE 2 Crystallization from guanidine hydrochloride solutions of different concentrations Concentration Guanidine No. hydrochloride Balance Crystal form 2.1 50 wt % 15.56 g 100% Form B 2.2 40 wt % 12.43 g  61% Form B  39% Form A 2.3 30 wt % 10.64 g  16% Form B  84% Form A 2.4 20 wt %  9.63 g 100% Form A 2.5 10 wt %  9.43 g 100% Form A

Example 3—Recrystallization of N-(Aminoiminomethyl)-2-Aminoacetic Acid from Water-Containing Solutions of Other Guanidine Compounds

[0151] Analogous to Example 2, aqueous solutions of various guanidine compounds were prepared in the respective concentrations (C) indicated. In 400 g of the respective solution, the respective indicated amount (M) of N-(aminoiminomethyl)-2-aminoacetic acid was dissolved at 80° C. After filtration at 80° C., another 100 g of the indicated aqueous solution of the respective guanidine compound was added and the clear solution was stirred at 80° C. for 1 hour. By slow cooling to 20° C. within 4 hours N-(aminoiminomethyl)-2-aminoacetic acid crystallized. The precipitated crystal aggregates were filtered off, washed 3 times with water of 20° C. and dried at 60° C. In each case, the indicated amount (A) of N-(aminoiminomethyl)-2-aminoacetic acid with a content (G) was obtained (see Table 3a/b).

[0152] Powder diffractograms were taken of the respective products and examined for the presence of the respective crystal forms, using the formula given above to determine the proportions of form A and form B.

TABLE-US-00003 TABLE 3a Recrystallization from water-containing solutions of guanidine compounds (not according to the invention) C % by M A G No. Guanidine compound weight g g % Crystal form 3.1 Melamine 0.3 16.98 11.13 99.3 100% Form A 3.2 N-cyanoguanidine 3.0 19.80 10.09 99.1 100% Form A 3.3 L-Arginine 10.0 18.37 11.98 99.2 100% Form A 3.4 N-(aminoimino-methyl)-N-methyl- 1.0 17.47 8.14 99.2 100% Form A 2-aminoacetic acid 3.5 Biguanide hydrochloride 50.0 13.72 7.13 99.3 100% Form A 3.6 N,N-dimethylbiguanide 30.0 10.06 5.81 99.1 100% Form A 3.7 N,N-dimethylbiguanide 2.0 22.30 11.89 99.3 100% Form A hydrochloride

TABLE-US-00004 TABLE 3b Recrystallization from water-containing solutions of guanidine compounds according to formula (I)-according to the invention C % by M A G No. Guanidine Compound weight g g % Crystal form 3.10 Guanidine nitrate 15 18.63 15.29 98.8  52% Form B  48% Form A 3.11 Guanidine 40 20.71 14.77 99.0  78% Form B amidosulfonate  22% Form A 3.12 Guanidine Acetate 50 17.39  7.89 99.2  94% Form B  6% Form A 3.13 N,N-dimethylguanidine 50 16.18  8.57 99.0  36% Form B hydrochloride  64% Form A 3.14 N,N-dimethylguanidine 30 30.13 15.61 99.1  51% Form B sulphate  49% Form A 3.15 N,N-diethylguanidine 50 27.11 13.56 99.2 100% Form B hydrochloride 3.16 N-methylguanidine 50 34.65 18.14 98.9 100% Form B sulphate 3.17 N-ethylguanidine 50 40.22 20.47 99.0  69% Form B sulphate  31% Form A 3.18 1-(Aminoiminomethyl)-4- 30 21.84 14.70 99.1 100% Form B methyl-piperazine sulfate 3.19 4-(aminoiminomethyl)- 30 18.11 10.02 99.3 100% Form B morpholine acetate

[0153] The guanidine compounds according to formula (I) of the invention thus preferentially induce crystal form B during crystallization of N-(aminoiminomethyl)-2-aminoacetic acid, although in some cases mixtures with form A also occur (cf. Table 3b). Other guanidines not according to the invention are not able to do this (cf. Table 3a).

[0154] Example 4 (Comparison)—Synthesis of N-(aminoiminomethyl)-2-aminoacetic acid from glycine and cyanamide in aqueous solution 112.6 g (1.5 mol) of glycine was dissolved in 300 g of water. To the solution was added 21.6 g (0.27 mol) of a50% sodium hydroxide solution, resulting in a pH of 8.4. A solution of 42.04 g (1.0 mol) of cyanamide dissolved in 42 g of water was added at 80° C. over the course of 4 hours. The post reaction was carried out at 80° C. for another hour. The obtained suspension was cooled to 20° C., filtered off, washed with water and dried at 60° C. 100.6 g N-(aminoiminomethyl)-2-aminoacetic acid with a content of 99.1% was obtained. The yield was 85.9%.

[0155] A powder diffractogram of the obtained fine acicular crystals indicated the sole presence of form A (100% form A).

Example 5 (Comparison)—Synthesis of N-(Aminoiminomethyl)-2-Aminoacetic Acid from Chloroacetic Acid and Guanidine Hydrochloride

[0156] As described in CN 101525305, 200 g NaOH (solid, 5.0 mol) was dissolved in 600 g water. At a maximum of 15° C., 480 g (5.03 mol) of solid guanidine hydrochloride was introduced. A water-containing solution of the guanidine base was obtained. 460 g (4.87 mol) of chloroacetic acid was dissolved in 460 g of water. To this was added 760 g of a 25% sodium hydroxide solution (corresponding to 4.75 mol NaOH) over 1 hour at 20° C. A water-containing solution of sodium chloroacetate was obtained. The guanidine solution was dosed over 2 hours to the solution of sodium chloroacetate heated to 40° C. The post reaction was carried out at 40° C. over a period of 24 hours. The white suspension obtained was filtered, washed with water and dried at 60° C. 404 g (71%) of GAA with a content of 98% was obtained. X-ray powder diffraction analysis showed that the obtained GAA was 100% in crystal form A. Despite the presence of guanidine (base) as a reactant, its concentration is not sufficient to affect the crystal form of GAA. This is consistent with Example 2, as a measurable effect was only seen above a concentration of 30 wt % guanidine hydrochloride. Such concentrations are not achieved in the production method according to CN 101525305, so that only crystal form A can be assumed for products produced in this way.

Example 6 (according to the invention)—Synthesis of N-(aminoiminomethyl)-2-Aminoacetic Acid from Glycine and Cyanamide in a 50% Solution of Guanidine Hydrochloride

[0157] A solution was prepared from 150 g of guanidine hydrochloride and 150 g of water. 112.6 g (1.5 mol) of glycine were dissolved therein and a pH of 8.4 was adjusted with 22.4 g (0.28 mol) of a 50% sodium hydroxide solution. A solution of 42.04 g (1.0 mol) of cyanamide dissolved in 42 g of water was added at 80° C. over the course of 4 hours. The post reaction was carried out at 80° C. for another hour. The obtained suspension was cooled to 20° C., filtered off, washed with water and dried at 60° C. 100.8 g of N-(aminoiminomethyl)-2-aminoacetic acid with a content of 99.1% was obtained. The yield was 86.0%.

[0158] A powder diffractogram of the obtained roundish crystal aggregates of radially radiating single crystals indicated the sole presence of form B (100% form B).

Example 7—Physicochemical Characterization of N-(Aminoiminomethyl)-2-Aminoacetic Acid of Form A and Form B

7.1 Melting or Decomposition Point

[0159] A Mettler DSC 3+instrument with 40 μl aluminum crucible was used for Dynamic Differential Scanning Calorimetry (DSC). The heating rate was 10 Kelvin per minute at a temperature range of 30 to 350° C. Approximately 1.4 mg each of the products of Examples 1 and 2.1 were weighed into aluminum crucibles and measured at atmospheric pressure (960 mbar at an altitude of 500 m above sea level).

[0160] The sample of Example 1 (=N-(aminoiminomethyl)-2-aminoacetic acid of form A) showed an onset (inflection point of the melting curve projected onto the baseline) of 280.5° C. and a peak temperature of the melting curve of 286.3° C. The total endothermic heat of fusion was 887 J/g (cf. FIG. 10). The product turned from white to brown during melting.

[0161] The sample of Example 2.1 (=N-(aminoiminomethyl)-2-aminoacetic acid form B) was measured analogously. It showed an onset of 272.5° C. and a peak at 280.4° C., the heat of fusion was 860 J/g, the discoloration was identical (see FIG. 11).

[0162] Form B thus melts approx. 6 to 8 Kelvin lower than form A and has a 27 J/g lower heat of fusion or 27 J/g higher lattice energy. In other words, 27 J/g less energy is required for form B than for form A in order to achieve the same energy melting state. Form B thus represents a metastable crystal form or a polymorph of N-(aminoiminomethyl)-2-aminoacetic acid that is higher in energy under normal pressure and temperature conditions.

[0163] This new metastable crystal modification form B is stable up to its melting point. A solid transformation from form B to form A or a reversible solid transformation of form A/form B cannot be observed. Thus, form B is an example of monotropic polymorphism.

7.2 Determination of Water Solubility

[0164] 100 g of water at 5° C. were provided. The product of Example 1 (=N-(aminoiminomethyl)-2-aminoacetic acid form A) was dissolved therein until saturation was reached and the dissolved amount was determined by backweighing. Then the temperature was increased to 20° C. and as much of the sample was added until the saturation point was reached again. The same was repeated at further temperatures, maximum at 95° C. An analogous measurement was made with the product of Example 2.1 (=N-(aminoiminomethyl)-2-aminoacetic acid form B). The solubility data obtained for both products were summarized graphically in FIG. 5.

[0165] Both crystal forms of N-(aminoiminomethyl)-2-aminoacetic acid dissolve better in water with increasing temperature. The inventive N-(aminoiminomethyl)-2-aminoacetic acid form B dissolves about 20% better than the known form Å at any temperature.

7.3 Determination of density

[0166] Crystals of N-(aminoiminomethyl)-2-aminoacetic acid form A of Example 1 were introduced into tetrachloromethane at 20° C., where they floated on the surface. By adding dichloromethane dropwise, the density of the liquid medium was decreased until the crystals just started to float in the liquid without rising and without sinking to the bottom. The density of the liquid phase was determined in a pycnometer. A density of 1.50+/−0.03 g/cm.sup.3 was measured.

[0167] The same procedure was followed with crystals of form B of Example 2.1. The density at 20° C. was determined to be 1.41+/−0.03 g/cm.sup.3.

[0168] Form B thus has a 6% lower density than form A. This correlates with the lower lattice energy of form B determined above. The measured crystal densities also agree with the X-ray crystal densities calculated from the respective lattice constants.

7.4 Determination of Dust Content

[0169] The product of Example 1 was sieved through a sieve with mesh size 63 μm (equivalent to 230 mesh -mesh size). 46 wt. % fines were obtained. An analogous procedure was followed with the sample of Example 2.1 consisting of polygonal, roundish crystal aggregates. Here, a fines content of less than 3 wt. % was determined. Low-dust materials, which can therefore be handled safely, should have a dust content (i.e. grain content <63 μm) of less than 10%. The product of Example 2.1 (N-(aminoiminomethyl)-2-aminoacetic acid of crystal form B) satisfies this, while Comparative Example 1 (N-(aminoiminomethyl)-2-aminoacetic acid of crystal form A) does not.

7.5 Determination of the Angle of Repose

[0170] The product of Example 1, consisting of matted acicular crystals, was poured through a funnel onto a flat surface using a device according to DIN ISO 4324. After removing the funnel, the angle of repose of the cone obtained was determined with an angle measuring device. It was approximately 45°. Accordingly, N-(aminoiminomethyl)-2-aminoacetic acid form A exhibits poor flow behavior. The granular product of Example 2.1 was measured anlogously. Here, a repose angle of about 25° was obtained. N-(aminoiminomethyl)-2-aminoacetic acid form B thus exhibits excellent flow behavior.

7.6 Determination of Bulk Density

[0171] A weighed quantity of the product of Example 1 was placed in a measuring cylinder and partially compacted by tapping it firmly twice on the laboratory bench. From the filling level of the measuring cylinder, the bulk density was determined to be 0.37 g/cm.sup.3. The same procedure was followed with the product of Example 2.1. Here, a bulk density of 0.62 g/cm.sup.3 was determined. N-(aminoiminomethyl)-2-aminoacetic acid of form B thus has a significantly increased bulk density, which is advantageous for packaging, transport and handling of the product.

7.7 Thermal Stability of N-(Aminoiminomethyl)-2-Aminoacetic Acid Form B

[0172] a)N-(aminoiminomethyl)-2-aminoacetic acid form B of Example 2.1 was placed in the drying oven for 6 hours at 120° C. X-ray powder diffraction was then used to determine the crystal form. This remained unchanged pure crystal form B.

[0173] b)N-(aminoiminomethyl)-2-aminoacetic acid form B of Example 2.1 was wetted with 20% water, incubated for 6 hours at 65° C. in a closed vessel, then dried. The X-ray powder diffractogram showed no change, form B remained stable.

[0174] c)N-(aminoiminomethyl)-2-aminoacetic acid form B of Example 2.1 was prepared as a 10% suspension in water. This suspension was stirred at 80° C. for 2 hours. It was then cooled, the solid filtered off and dried. X-ray powder diffraction showed that a mixture of crystals forms A and B was present.

[0175] d)N-(aminoiminomethyl)-2-aminoacetic acid form B of Example 2.1 was dissolved in water at 80° C., largely recrystallized by cooling the solution, filtered off and dried. X-ray powder diffraction yielded pure crystal form A.

[0176] N-(aminoiminomethyl)-2-aminoacetic acid form B is thus very stable in solid form, but has a tendency to change to crystal form A via the water-containing solution. This behavior also confirms the metastable crystal structure of form B.

7.8 Physical Property of Mixtures of Form A and Form B

[0177] In Example 7.6, the bulk density of GAA form A was determined to be 0.37 g/cm.sup.3 and that of GAA form B 0.62 g/cm.sup.3. Starting from pure substance samples of GAA form A or form B, mixtures of the two forms were weighed in and mixed by shaking (not grinding or mortaring!). The bulk densities of the crystal mixtures produced in this way were determined.

TABLE-US-00005 TABLE 5 Bulk density in the crystal mixture Weight Weight proportion Form A proportion Form B Bulk density 100%  0% 0.62 g/cm.sup.3  75% 25% 0.59 g/cm.sup.3  50% 50% 0.53 g/cm.sup.3  25% 75% 0.41 g/cm.sup.3  0% 100%  0.37 g/cm.sup.3

[0178] It can be seen that the bulk density increases as the proportion of GAA form B increases, whereby from 50% form B the bulk density is advantageously above the arithmetic mean of the two end members (cf. also FIG. 8).