阅读说明：本技术 L-草铵膦的晶型及其制备方法和应用 (Crystal form of L-glufosinate-ammonium, preparation method and application thereof ) 是由 姜宇华 于 2021-06-21 设计创作，主要内容包括：本发明公开了L-草铵膦的晶型及其制备方法和应用,其晶型包括铵盐形式A、B以及两性离子形式C,这些晶型在稳定性、引湿性、存储性等方面表现出优异的效果,有利于除草药物的制备、分离以及储存,同时溶解性佳、药代动力学好,进而有利于提高除草药物控制杂草的水平和速度。(The invention discloses a crystal form of L-glufosinate-ammonium, a preparation method and application thereof, wherein the crystal form comprises an ammonium salt form A, B and a zwitter-ion form C, the crystal forms show excellent effects in the aspects of stability, hygroscopicity, storage property and the like, are favorable for preparation, separation and storage of a weeding medicament, and are good in solubility and pharmacokinetics, so that the level and speed of the weeding medicament for controlling weeds are improved.)

1. The crystal of L-glufosinate-ammonium is characterized in that the crystal is a crystal form A of L-glufosinate-ammonium, and an X-ray powder diffraction pattern of the crystal has characteristic peaks at the 2 theta angle of 16.658 degrees +/-0.2 degrees, 18.139 degrees +/-0.2 degrees, 23.960 degrees +/-0.2 degrees, 25.458 degrees +/-0.2 degrees and 28.380 degrees +/-0.2 degrees.

2. The crystal according to claim 1, characterized in that the form a of L-glufosinate further has an X-ray powder diffraction pattern having characteristic peaks at one or more of 2 Θ angles of 9.916 ° ± 0.2 °, 28.879 ° ± 0.2 °; and/or the crystal form A of the L-glufosinate-ammonium shows an endothermic peak in a spectrum measured by differential scanning calorimetry, and the peak temperatures of the two endothermic peaks are 129.65 +/-2 ℃ respectively; and/or the crystal form A of the L-glufosinate-ammonium is an anhydrous ammonium salt crystal form.

3. The crystal of L-glufosinate-ammonium is characterized in that the crystal is a crystal form B of L-glufosinate-ammonium, and an X-ray powder diffraction pattern of the crystal has characteristic peaks at the 2 theta angle of 9.484 degrees +/-0.2 degrees, 12.163 degrees +/-0.2 degrees, 17.098 degrees +/-0.2 degrees, 22.540 degrees +/-0.2 degrees and 34.899 degrees +/-0.2 degrees.

4. The crystal of claim 3, characterized in that the X-ray powder diffraction pattern of form B of L-glufosinate further has characteristic peaks at one or more of 2 θ angles of 10.833 ° ± 0.2 °, 19.240 ° ± 0.2 °, 21.481 ° ± 0.2 °, 25.202 ° ± 0.2 °, 32.418 ° ± 0.2 °, 34.022 ° ± 0.2 °; and/or the crystal form B of the L-glufosinate-ammonium shows an endothermic peak in a spectrum measured by differential scanning calorimetry, and the peak temperature of the endothermic peak is 134.07 +/-2 ℃.

5. The crystal of L-glufosinate-ammonium is characterized in that the crystal is a crystal form C of L-glufosinate-ammonium, and an X-ray powder diffraction pattern of the crystal has characteristic peaks at positions with 2 theta angles of 16.018 degrees +/-0.2 degrees, 19.067 degrees +/-0.2 degrees, 19.338 degrees +/-0.2 degrees and 21.581 degrees +/-0.2 degrees.

6. The crystal of claim 5, characterized in that the X-ray powder diffraction pattern of form C of L-glufosinate further has characteristic peaks at one or more of 2 θ angles of 16.620 ° ± 0.2 °, 17.460 ° ± 0.2 °, 29.159 ° ± 0.2 °, 34.477 ° ± 0.2 °, 35.280 ° ± 0.2 °; and/or the crystal form C of the L-glufosinate-ammonium shows two endothermic peaks in a spectrum measured by differential scanning calorimetry, and the peak temperatures of the two endothermic peaks are 139.14 +/-2 ℃.

7. A method for producing a crystal according to claim 1 or 2, comprising:

dispersing L-glufosinate-ammonium hydrochloride in water to form a dispersion, introducing ammonia gas to neutralize the dispersion, controlling the pH value of the dispersion to be 6-8, concentrating the dispersion, adding an organic solvent at a temperature of T1, cooling the dispersion to-10-15 ℃ at a cooling rate with a difference of an external temperature and an internal temperature of 1-5K, preserving the temperature, separating out a solid, filtering the solid, drying the obtained solid, mixing and refluxing the dried solid and the organic solvent, cooling the dispersion to-10-15 ℃ at a cooling rate with a difference of an external temperature and an internal temperature of 1-5K, preserving the temperature, separating out the solid, filtering the obtained solid, and drying the obtained solid to obtain a crystal form A of L-glufosinate-ammonium, wherein T1 is between 50 ℃ and the boiling point of the organic solvent; or the like, or, alternatively,

dispersing L-glufosinate-ammonium hydrochloride in water to form a dispersion, introducing ammonia gas to neutralize the dispersion, controlling the pH value of the dispersion to be 6-8, concentrating the dispersion, controlling the temperature to be 20-40 ℃, adding an organic solvent at a dropping speed of 0.1-10g/min, separating out solids in the dropping process, preserving heat after dropping is finished, then cooling to-10-15 ℃, preserving heat, separating out solids, filtering to obtain solids, drying the obtained solids, mixing and refluxing the dried solids and the organic solvent, then cooling at a cooling rate with the difference of the external temperature and the internal temperature of 1-5K, cooling to-10-15 ℃, preserving heat, separating out the solids, filtering to obtain the solids, and drying the obtained solids to obtain the crystal form A of the L-glufosinate-ammonium.

8. A method for producing a crystal according to claim 3 or 4, characterized by comprising:

dispersing L-glufosinate-ammonium hydrochloride in water to form a dispersion, introducing ammonia gas to neutralize the dispersion, controlling the pH value of the dispersion to be 6-8, concentrating the dispersion, adding an organic solvent at a temperature of T2, cooling the dispersion to-10-15 ℃ at a cooling rate with a difference of 1-5K between an external temperature and an internal temperature, preserving the temperature, separating out a solid, filtering the solid to obtain a solid, and drying the solid to obtain a crystal form B of the L-glufosinate-ammonium, wherein the T2 is between 50 ℃ and the boiling point of the organic solvent.

9. A method for producing a crystal according to claim 5 or 6, comprising:

dispersing L-glufosinate-ammonium hydrochloride in water to form a dispersion, introducing ammonia gas to neutralize the dispersion, controlling the pH value of the dispersion to be 1-4, concentrating the dispersion, adding an organic solvent at a temperature of T3, cooling the dispersion to-10-15 ℃ at a cooling rate with a difference of 1-5K between an external temperature and an internal temperature, preserving the temperature, separating out a solid, filtering the solid to obtain a solid, and drying the solid to obtain a crystal form C of the L-glufosinate-ammonium, wherein the T3 is between 50 ℃ and the boiling point of the organic solvent.

10. A herbicidal composition comprising an active ingredient and a carrier, characterized in that the active ingredient comprises the crystal of any one of claims 1 to 6.

Technical Field

The invention particularly relates to a crystal form of L-glufosinate-ammonium, a preparation method and application thereof.

Background

Glufosinate, a contact type biocidal herbicide, has the characteristics of wide herbicidal spectrum, low toxicity, high activity, good environmental compatibility and the like, and has the speed of exerting the active action slower than paraquat, but better than glyphosate; the herbicide is a non-selective herbicide coexisting with glyphosate and paraquat and has wide application prospect; many weeds are sensitive to glufosinate and can be used as a substitute for glyphosate in areas where glyphosate is resistant; wherein, the L-glufosinate-ammonium is an active ingredient in the racemic glufosinate-ammonium, and the herbicidal activity of the L-glufosinate-ammonium is 2 times of that of the racemic body. In addition, the crystal structure of the active ingredient of the herbicide often causes the difference of various physicochemical properties of the herbicide, such as solubility, dissolution rate, storage stability, hardness and the like, and the difference directly affects the preparation process, storage method, separation method, pharmacokinetic performance and the like of the herbicide, thereby affecting the level and speed of the herbicide for controlling weeds, the difficulty degree of specific operation and the like.

At present, a plurality of synthetic methods are reported for L-glufosinate ammonium salt, including biological methods and chemical methods. However, the research on the crystal form is relatively few, and CN111065270 describes that crystal forms a to E of L-glufosinate are obtained by separation from a glutamic acid composition and screening, wherein the crystal form a is metastable and tends to be converted into other forms, ion chromatography shows that the content of ammonium ions is 6.4%, which indicates that the crystal form is a mixed crystal of an ammonium salt structure and a zwitterion structure, the crystal form B is a crystal form of L-glufosinate zwitterion, and the crystal form C is metastable and is easy to be converted into the form a and the form B; crystalline form D is prepared from several room temperature or elevated temperature slurries of polymorph screens, typically as a mixture with form a, and both form B and form D are anhydrous crystalline forms of the free form of L-glufosinate; the 1H NMR spectrum of form E was consistent with that of L-glufosinate, but the peak shift suggests potential ionization differences, and IC analysis showed only a small amount of ammonium and a stoichiometric amount of chloride, suggesting that form E is not the form of L-glufosinate, but rather the form of L-glufosinate hydrochloride.

However, the above-mentioned crystalline form of L-glufosinate still shows one or more deficiencies in stability, hygroscopicity, etc., and thus it is very important to deeply study the polymorphism of the herbicidal drug and find a crystalline form having good properties.

Disclosure of Invention

The invention aims to solve the problems that: provides a novel crystal form A of L-glufosinate-ammonium, which is in the form of ammonium salt of L-glufosinate-ammonium and has excellent effects on the aspects of stability, hygroscopicity and the like.

The invention also provides a novel crystal form B of the L-glufosinate-ammonium, which is in an ammonium salt form of the L-glufosinate-ammonium and has excellent effects in the aspects of stability, hygroscopicity and the like.

The invention also provides a novel crystal form C of the L-glufosinate-ammonium, which is a zwitter-ion form of the L-glufosinate-ammonium and has excellent effects on the aspects of stability, hygroscopicity and the like.

The invention also provides a preparation method of the crystals and application of the crystals in preparation of herbicides.

In order to achieve the purpose, the invention adopts a technical scheme that:

a crystal of L-glufosinate-ammonium, which is a crystal form A of L-glufosinate-ammonium, and has a characteristic peak in an X-ray powder diffraction pattern at a 2 theta angle of 16.658 DEG +/-0.2 DEG, 18.139 DEG +/-0.2 DEG, 23.960 DEG +/-0.2 DEG, 25.458 DEG +/-0.2 DEG and 28.380 DEG +/-0.2 deg.

In some embodiments of the invention, the X-ray powder diffraction pattern of form a of the L-glufosinate further has characteristic peaks at one or more of angles 2 Θ of 9.916 ° ± 0.2 °, 28.879 ° ± 0.2 °.

According to a specific aspect of the present invention, the X-ray powder diffraction pattern of crystalline form a of L-glufosinate further has characteristic peaks at one or more of angles 2 θ of 19.361 ° ± 0.2 °, 19.859 ° ± 0.2 °, 21.395 ° ± 0.2 °, 21.708 ° ± 0.2 °.

According to a specific aspect of the present invention, the X-ray powder diffraction pattern of the crystalline form a of L-glufosinate-ammonium is shown in fig. 1.

According to some specific aspects of the present invention, the crystal form a of L-glufosinate-ammonium shows an endothermic peak in a differential scanning calorimetry measured spectrum, and the peak temperatures of the two endothermic peaks are 129.65 ± 2 ℃.

According to a particular aspect of the invention, the crystalline form a of L-glufosinate is an anhydrous single glufosinate ammonium salt crystalline form.

The invention also provides a crystal of L-glufosinate-ammonium, which is a crystal form B of the L-glufosinate-ammonium, and an X-ray powder diffraction pattern of the crystal has characteristic peaks at the 2 theta angles of 9.484 degrees +/-0.2 degrees, 12.163 degrees +/-0.2 degrees, 17.098 degrees +/-0.2 degrees, 22.540 degrees +/-0.2 degrees and 34.899 degrees +/-0.2 degrees.

In some embodiments of the invention, the X-ray powder diffraction pattern of crystalline form B of L-glufosinate further has characteristic peaks at one or more of angles 2 θ of 10.833 ° ± 0.2 °, 19.240 ° ± 0.2 °, 21.481 ° ± 0.2 °, 25.202 ° ± 0.2 °, 32.418 ° ± 0.2 °, 34.022 ° ± 0.2 °.

In some embodiments of the invention, the X-ray powder diffraction pattern of crystalline form B of L-glufosinate-ammonium may also have characteristic peaks at one or more of angles 2 θ of 19.638 ° ± 0.2 °, 24.879 ° ± 0.2 °, 27.927 ° ± 0.2 °, 37.139 ° ± 0.2 °.

According to a specific aspect of the present invention, the X-ray powder diffraction pattern of the crystalline form B of L-glufosinate-ammonium is shown in fig. 3.

According to some specific aspects of the present invention, the crystalline form B of L-glufosinate-ammonium exhibits an endotherm in a differential scanning calorimetry (dsc) measurement profile, the peak temperature of the endotherm being 134.07 ± 2 ℃.

The invention also provides a crystal of L-glufosinate-ammonium, which is a crystal form C of the L-glufosinate-ammonium, and an X-ray powder diffraction pattern of the crystal has characteristic peaks at the 2 theta angles of 16.018 degrees +/-0.2 degrees, 19.067 degrees +/-0.2 degrees, 19.338 degrees +/-0.2 degrees and 21.581 degrees +/-0.2 degrees.

In some embodiments of the invention, the X-ray powder diffraction pattern of crystalline form C of L-glufosinate further has characteristic peaks at one or more of 2 Θ angles of 16.620 ° ± 0.2 °, 17.460 ° ± 0.2 °, 29.159 ° ± 0.2 °, 34.477 ° ± 0.2 °, 35.280 ° ± 0.2 °.

According to a specific aspect of the present invention, the X-ray powder diffractogram of crystalline form C of L-glufosinate may further have characteristic peaks at one or more of 9.802 ° ± 0.2 °, 18.139 ° ± 0.2 °, 19.834 ° ± 0.2 °, 20.600 ° ± 0.2 °, 21.984 ° ± 0.2 °, 23.723 ° ± 0.2 °, 25.439 ° ± 0.2 °, 25.738 ° ± 0.2 °, 26.758 ° ± 0.2 °, 27.082 ° ± 0.2 °, 28.395 ° ± 0.2 °, 30.983 ° ± 0.2 °, 32.584 ° ± 0.2 °, 33.100 ° ± 0.2 °, 34.242 ° ± 0.2 °, 36.768 ° ± 0.2 °, 37.075 ° ± 0.2 °, 39.535 ° ± 0.2 ° at the 2 θ angle.

According to a specific aspect of the present invention, the X-ray powder diffraction pattern of the crystalline form C of L-glufosinate-ammonium is shown in fig. 5.

According to some specific aspects of the present invention, the crystal form C of L-glufosinate-ammonium shows two endothermic peaks in a differential scanning calorimetry measured spectrum, and the peak temperatures of the one endothermic peak are 139.14 ± 2 ℃.

The invention also provides a preparation method of the L-glufosinate-ammonium crystal form A, which comprises the following steps:

dispersing L-glufosinate-ammonium hydrochloride in water to form dispersion, introducing ammonia gas to neutralize and control the pH value of the dispersion to be 6-8, concentrating, adding an organic solvent at the temperature of T1, cooling at a cooling rate with the difference Tj-Tr-1 to-5K between the external temperature (Tj) and the internal temperature (Tr) to-10-15 ℃, preserving heat, separating out solids, filtering to obtain solids, drying the obtained solid, mixing the dried solid with an organic solvent for reflux, then cooling at a cooling rate with the difference Tj-Tr between the external temperature (Tj) and the internal temperature (Tr) of 1-5K to-10-15 ℃, preserving heat, precipitating the solid, filtering to obtain the solid, drying the obtained solid to obtain a crystal form A of L-glufosinate-ammonium, wherein the temperature of T1 is between 50 ℃ and the boiling point of an organic solvent; or the like, or, alternatively,

dispersing L-glufosinate-ammonium hydrochloride in water to form a dispersion, introducing ammonia gas to neutralize the dispersion, controlling the pH value of the dispersion to be 6-8, concentrating the dispersion, controlling the temperature to be 20-40 ℃, adding an organic solvent at a dropping speed of 0.1-10g/min, separating out solids in the dropping process, preserving heat after dropping is finished, then cooling to-10-15 ℃, preserving heat, separating out solids, filtering to obtain solids, drying the obtained solids, mixing and refluxing the dried solids and the organic solvent, then cooling at a cooling rate of a difference Tj-Tr between an external temperature (Tj) and an internal temperature (Tr) to-10-15 ℃, preserving heat, separating out the solids, filtering to obtain solids, and drying the obtained solids to obtain a crystal form A of the L-glufosinate-ammonium.

The invention also provides a preparation method of the L-glufosinate-ammonium crystal form B, which comprises the following steps:

dispersing L-glufosinate-ammonium hydrochloride in water to form a dispersion, introducing ammonia gas to neutralize the dispersion, controlling the pH value of the dispersion to be 6-8, concentrating the dispersion, adding an organic solvent at a temperature of T2, cooling the dispersion to-10-15 ℃ at a cooling rate with a difference Tj-Tr of an external temperature (Tj) and an internal temperature (Tr) of 1-5K, keeping the temperature, separating out a solid, filtering the solid to obtain a solid, and drying the solid to obtain a crystal form B of the L-glufosinate-ammonium, wherein the temperature of T2 is between 50 ℃ and the boiling point of the organic solvent.

The invention also provides a preparation method of the L-glufosinate-ammonium crystal form C, which comprises the following steps:

dispersing L-glufosinate-ammonium hydrochloride in water to form a dispersion, introducing ammonia gas to neutralize the dispersion, controlling the pH value of the dispersion to be 1-4, concentrating the dispersion, adding an organic solvent at a temperature of T3, cooling the dispersion to-10-15 ℃ at a cooling rate with a difference Tj-Tr of an external temperature (Tj) and an internal temperature (Tr) of 1-5K, keeping the temperature, separating out a solid, filtering the solid to obtain a solid, and drying the solid to obtain a crystal form C of the L-glufosinate-ammonium, wherein the T3 is between 50 ℃ and the boiling point of the organic solvent.

According to some preferred aspects of the present invention, the organic solvent is a combination of one or more selected from the group consisting of an alcohol solvent, a ketone solvent and a nitrile solvent.

Further, the alcohol solvent is one or more selected from methanol, ethanol and isopropanol.

Further, the ketone solvent includes acetone.

Further, the nitrile solvent includes acetonitrile.

According to some preferred aspects of the present invention, in the process of preparing form a, form B or form C of L-glufosinate, the dispersion is preferably concentrated to 30-80% at a concentration step after the introduction of ammonia gas.

According to some preferred aspects of the present invention, in the process of preparing the crystal form a, the crystal form B or the crystal form C of L-glufosinate-ammonium, the feeding mass ratio of L-glufosinate-ammonium hydrochloride to the organic solvent is 1: 1-20.

According to some preferred aspects of the present invention, in the process of preparing the crystal form a, the crystal form B or the crystal form C of L-glufosinate-ammonium, the feeding mass ratio of water to the organic solvent is 1: 1-15.

According to some preferred aspects of the present invention, in one method for preparing form A of L-glufosinate-ammonium, the dropping speed of the organic solvent is 1 to 5 g/min.

The invention also provides a herbicide composition, which comprises an active ingredient and a carrier, wherein the active ingredient comprises the crystal.

The invention also provides the application of the crystal in preparing herbicides.

To aid in understanding the various embodiments disclosed herein, the following description is provided:

the X-ray powder diffraction pattern is characteristic for a particular crystalline form. To determine if it is the same as the known crystal type, care should be taken with respect to the relative positions of the peaks (i.e., 2 θ) rather than their relative intensities. This is because the relative intensities of the spectra vary due to the dominant orientation effect resulting from differences in crystal conditions, particle size and other assay conditions, particularly the low intensity peak (intensity less than 20%) may not be present in some cases, the relative intensities of the diffraction peaks are not characteristic of the determination of the crystal form, in fact, the relative intensities of the diffraction peaks in the XRPD spectra are related to the preferred orientation of the crystals, and the peak intensities shown herein are illustrative and not used for absolute comparison. In addition, it is known in the art that when crystals of a compound are measured by X-ray diffraction, a certain measurement error of about ± 0.2 ° may exist in 2 θ values of the same crystal form due to the influence of a measuring instrument or measuring conditions, etc. Therefore, this error should be taken into account when determining each crystalline structure. The peak position is usually expressed in the XRD pattern by the 2 theta angle or the d value of the interplanar distance, with a simple conversion relationship between them: where d represents the interplanar spacing d, λ represents the wavelength of the incident X-rays, and θ is the diffraction angle. It should also be noted that in the identification of mixtures, a partial loss of diffraction lines may occur due to, for example, a reduction in the content. In addition, due to the influence of experimental factors such as sample height, an overall shift in peak angle is caused, and a certain shift is usually allowed. Thus, it will be understood by those skilled in the art that the X-ray diffraction patterns of the crystalline forms referred to herein need not be identical to the X-ray diffraction patterns of the examples referred to herein, that "the same XRPD patterns" as used herein does not mean absolute identity, that the same peak positions may differ by + -0.2 deg. (or more) and that the peak intensities allow for some variability. Any crystalline form having the same or similar pattern as the characteristic peaks in these maps is within the scope of the present application. One skilled in the art can compare the profiles listed in this application to a profile of an unknown crystalline form to confirm whether the two sets of profiles reflect the same or different crystalline forms.

On the basis of a specific X-ray crystal diffraction pattern, a person skilled in the art is generally allowed to select several characteristic peaks to define the crystal form, and the selection of the characteristic peaks is comprehensively considered for a certain purpose without strict limitation, for example, the person skilled in the art is more inclined to select a peak with higher relative intensity, a peak with relatively low angle and a characteristic peak with complete peak shape, and select a characteristic peak which is enough to be distinguished from other crystals, so that the characteristic peaks have the significance of being distinguished, identified and identified. Thus, it cannot be concluded that a different crystal form is constituted or that the range of crystal forms is beyond the original request merely because the combination of selected characteristic peaks changes.

DSC measures the transition temperature when a crystal absorbs or releases heat due to a change in its crystal structure or melting of the crystal. For the same crystal form of the same compound, the thermal transition temperature and melting point errors are typically within about 5 ℃ in a continuous analysis. When we say that a compound has a given DSC peak or melting point, this means that the DSC peak or melting point ± 5 ℃. It is noted that the DSC peak or melting point for the mixture may vary over a larger range. Furthermore, the melting temperature is related to the rate of temperature rise due to decomposition that accompanies the process of melting the substance.

It should be noted that the numerical values and numerical ranges mentioned in this application should not be construed narrowly as numerical values or numerical ranges per se, and those skilled in the art will appreciate that they can be varied in accordance with specific technical circumstances and that they can be varied widely around specific numerical values without departing from the spirit and principles of this application.

Due to the application of the technical scheme, compared with the prior art, the invention has the following advantages:

the invention provides a novel crystal form of L-glufosinate-ammonium, in particular to an ammonium salt form A, B of L-glufosinate-ammonium and a zwitter ion form C of L-glufosinate-ammonium, wherein the crystal forms show excellent effects in at least one of the aspects of stability, hygroscopicity, storage property and the like, are favorable for preparation, separation and storage of a herbicide, and are simultaneously good in solubility and pharmacokinetics, so that the level and speed of the herbicide for controlling weeds are improved.

Drawings

FIG. 1 is an XRPD spectrum of form A of L-glufosinate prepared in example 1;

FIG. 2 is a DSC spectrum of form A of L-glufosinate prepared in example 1;

FIG. 3 is an XRPD spectrum of form B of L-glufosinate prepared in example 2;

FIG. 4 is a DSC spectrum of form B of L-glufosinate prepared in example 2;

FIG. 5 is an XRPD spectrum of form C of L-glufosinate prepared in example 3;

FIG. 6 is a DSC of form C of L-glufosinate prepared in example 3.

Detailed Description

The above-described scheme is further illustrated below with reference to specific examples; it is to be understood that these embodiments are provided to illustrate the general principles, essential features and advantages of the present invention, and the present invention is not limited in scope by the following embodiments; the implementation conditions used in the examples can be further adjusted according to specific requirements, and the implementation conditions not indicated are generally the conditions in routine experiments.

Not specifically illustrated in the following examples, all starting materials are commercially available or prepared by methods conventional in the art.

In this application, the test instruments and conditions used for the experiments are as follows:

the crystal form analysis of the product was carried out by an X-ray powder diffractometer (XRD, Rigaku D/Max-2500 type, Cu ka ray, λ K α ═ 0.15406nm), with emission voltage and current of 40kV and 100mA, respectively, scanning range of 2-40 °, scanning step of 0.02 °, and scanning rate of 8 °/min.

2. Differential Scanning Calorimetry (DSC): samples of 5-10mg were placed in aluminum crucibles and placed in the instrument with a nitrogen flow set at 50, 200ml/min, the temperature was increased from 30 to 200 degrees at a rate of 10 ℃/min and analyzed using STAR software from Mettler Toledo.

In the following description, Tj-Tr means "a difference between an external temperature and an internal temperature", where the external temperature corresponds to a temperature of a cold source (a portion that absorbs heat to reduce the temperature), the internal temperature refers to a temperature of a mixed solution, and a temperature reduction rate Tj-Tr of 1K to 5K means that the difference between the external temperature and the internal temperature is always maintained at 1 to 5 ℃ in the temperature reduction process, that is, the external temperature and the internal temperature are both maintained dynamically changed and are always maintained at 1 to 5 ℃.

Example 1: preparation of crystal form A of L-glufosinate-ammonium

The method comprises the following steps: adding L-glufosinate-ammonium hydrochloride (100g, 0.46mol) into water (200g), introducing ammonia gas to adjust the pH value to 7, carrying out reduced pressure distillation and concentration to 75%, adding methanol (600g) at 60 ℃, cooling to 5 ℃ at the cooling rate of Tj-Tr-2K, preserving heat for 24 hours, separating out solids, filtering, drying, adding methanol (300g) to reflux for 24 hours, cooling to 5 ℃ at the cooling rate of Tj-Tr-2K, preserving heat for 24 hours, separating out solids, filtering, and drying to obtain the crystal form A of the L-glufosinate-ammonium with the HPLC purity of 99%.

The method 2 comprises the following steps: adding L-glufosinate-ammonium hydrochloride (100g, 0.46mol) into water (200g), introducing ammonia gas to adjust the pH value to 7, carrying out reduced pressure distillation and concentration to 50%, cooling to 30 ℃, adding methanol (600g) at the temperature at the dropping speed of 2g/min, slowly separating out solid in the dropping process, preserving heat for 6 hours after dropping is finished, then cooling to 5 ℃, preserving heat for 24 hours, filtering, drying, refluxing in methanol (300g) for 12 hours, then cooling at the cooling rate of the difference of the external temperature and the internal temperature of 2K, preserving heat to 5 ℃, separating out solid, filtering to obtain solid, and drying the obtained solid to obtain the crystal form A of the L-glufosinate-ammonium.

The solid obtained in the method 1 was subjected to XRPD measurement, and the spectrum showed in fig. 1, characteristic peaks at diffraction angles 2 θ of 16.658 °, 18.139 °, 23.960 °, 25.458 ° and 28.380 °, and the error range of 2 θ was ± 0.2 degrees. The x-ray powder diffraction data are shown in table 1.

Table 1: XRPD pattern details of crystal form A of L-glufosinate-ammonium

DSC results (fig. 2) showed an absorption peak at 129.58 ℃ (peak temperature); meanwhile, the quantitative content is 99 percent calculated by a standard sample without crystal water, and the ion chromatographic analysis shows that the ammonium content is 9.0 percent and is basically consistent with that expected by theoretical monoammonium salt (9.1 percent), which indicates that the crystal form is the anhydrous ammonium salt crystal of the glufosinate-ammonium.

The solid obtained by the method 2 is also subjected to XRPD test, and the test spectrogram is basically consistent with that in figure 1, which shows that the obtained solid is the crystal form A of the L-glufosinate-ammonium.

Example 2: preparation of crystal form B of L-glufosinate-ammonium

Adding L-glufosinate-ammonium hydrochloride (100g, 0.46mol) into water (200g), introducing ammonia gas to adjust the pH value to 7, carrying out reduced pressure distillation and concentration to 50%, adding methanol (600g) at 60 ℃, cooling to 5 ℃ at the cooling rate of Tj-Tr-2K, preserving heat for 5 days, separating out solids, filtering, and drying to obtain the crystal form B of the L-glufosinate-ammonium.

The solid obtained above was subjected to XRPD measurement, and the spectrum showed in fig. 3, characteristic peaks at diffraction angles 2 θ of 9.484 °, 12.163 °, 17.098 °, 22.540 ° and 34.899 °, with a 2 θ error range of ± 0.2 degrees. The x-ray powder diffraction data are shown in table 2.

Table 2: XRPD pattern details of crystal form B of L-glufosinate-ammonium

DSC results (fig. 4) showed an absorption peak at 134.07 ℃ (peak temperature); the quantitative content was 92% based on the standard containing water of crystallization and the ion chromatography analysis showed an ammonium content of 8.4% essentially in accordance with what would be expected for the theoretical mono-ammonium salt (8.4%), indicating that this crystalline form contains ammonium salt crystals with one water of crystallization.

Example 3: preparation of crystal form C of L-glufosinate-ammonium

Adding L-glufosinate-ammonium hydrochloride (100g, 0.46mol) into water (200g), introducing ammonia gas to adjust the pH value to be 2.5, carrying out reduced pressure distillation and concentration to 50%, adding methanol (300g) at 60 ℃, cooling to 5 ℃ at the cooling rate of Tj-Tr ═ 1K, preserving heat for 24 hours, separating out solids, filtering and drying to obtain the crystal form C of the L-glufosinate-ammonium.

The solid obtained above was subjected to XRPD measurement, and the spectrum showed in fig. 5, characteristic peaks at diffraction angles 2 θ of 16.018 °, 19.067 °, 19.338 ° and 21.581 °, and the error range of 2 θ was ± 0.2 degrees. The x-ray powder diffraction data are shown in table 3.

Table 3: XRPD pattern details of crystal form C of L-glufosinate-ammonium

DSC results (fig. 6) showed an absorption peak at 139.14 ℃ (peak temperature), respectively; the standard sample without crystal water is used for quantification, the content is 99 percent, and the content of ammonium is 0.12 percent by ion chromatographic analysis. Indicating that the crystal form C of the L-glufosinate-ammonium is a zwitterionic crystal form without crystal water.

Comparative example

Adding L-glufosinate-ammonium hydrochloride (100g, 0.46mol) into water (200g), introducing ammonia gas to adjust the pH value to 7, carrying out reduced pressure distillation and concentration to 85%, adding methanol (600g) at 60 ℃, cooling with ice water, rapidly cooling to 20 ℃, and preserving heat for 7 days at the temperature to obtain a crystal form of L-glufosinate-ammonium, wherein the crystal form is proved to be a crystal form A in patent CN1110625270A, and after filtering, standing for 2 days, obvious water absorption phenomenon occurs, and water absorption is formed into an aqueous solution.

Example 4: moisture absorption detection

The experimental scheme is as follows: 100g of solid is respectively kept for 14 days under different humidities, the quality of the solid is repeatedly tested, and the appearance of the solid is visually tested to judge whether the crystal form has hygroscopicity, wherein specific results are shown in a table 4.

TABLE 4

Serial number

Crystal form

Quality of

Appearance of the product

Storage temperature

Humidity

Change in mass (%)

1

A

100.00g

White solid

20℃

65％

+0.02

2

B

100.00g

White solid

20℃

65％

+0.03

3

C

100.00g

White solid

20℃

65％

+0.02

4

A

100.00g

White solid

20℃

80％

+1.45

5

B

100.00g

White solid

20℃

80％

+1.55

6

C

100.00g

White solid

20℃

80％

+1.54

The experiment shows that: at lower relative humidity, there is no significant hygroscopicity. At higher relative humidity, the hygroscopicity is also very low.

Example 5: stability test

Experimental mode: the crystal form A, B, C was stored at 60 ℃ for 7 days and tested again for crystal form change, the specific results are shown in table 5.

TABLE 5

Serial number

Crystal form

Quality of

Temperature of

Humidity

Crystal form

Appearance of the product

1

A

100g

60℃

65％

Without change

Without change

2

B

100g

60℃

65％

Without change

Without change

3

C

100g

60℃

65％

Without change

Without change

Experiments show that: the crystal form A, B and C stability of L-glufosinate-ammonium is excellent compared with the crystal form in CN111065270A, and the L-glufosinate-ammonium is very favorable for packaging and transportation

Formulation preparation and field drug effect experiment

The invention is further explained in detail by combining specific preparation formulation and field efficacy experiments, and the protected crystal form active compound meets the requirements of an aqueous solution, and can be developed into a single preparation formulation or a compound preparation formulation. The following percentages are by weight.

The method combining preparation processing and field efficacy test is adopted below. The test medicament is provided by Jiangsu Qizhou green chemical industry Co.

The first application embodiment:

table 610% refined glufosinate solution

Name of material	Formulation ratio
		Fine glufosinate-ammonium (L-crystal of glufosinate-ammonium)	10％
Surface active agent	3％
		Water (W)	Complement

The dosage forms prepared by the crystal form A of the L-glufosinate-ammonium prepared in example 1, the crystal form B of the L-glufosinate-ammonium prepared in example 2 and the crystal form A (prepared by a comparative example) in patent CN111065270A are respectively used for preparing the dosage forms to carry out field efficacy experiments. The physical and chemical stability of the aqueous product prepared by the crystal forms A and B is detected, the production and use requirements are met, and meanwhile, field experiments are carried out on different weeds. The using amount is 120 g/mu.

Referring to 'pesticide field efficacy test criteria', each plot is investigated for 5 points, each point is 1 square meter, the species, total plant number, poisoning symptoms, dead plant number and the like of each treated weed are recorded 7 days after the pesticide is applied, then the plant control effect results are counted, and the weed death rate is specifically calculated and counted.

TABLE 7 investigation results of the control efficacy of the plants 7 days after drug administration

And (4) conclusion:

compared with the crystal form A in the patent CN1110625270, the drug effect of the ammonium salt crystal forms A and B in the patent is obviously 5-10% higher, and the single crystal form of the ammonium salt is supposed to be beneficial to the absorption of crops, so that the weeding effect is achieved.

The above embodiments are merely illustrative of the technical ideas and features of the present invention, and the purpose thereof is to enable those skilled in the art to understand the contents of the present invention and implement the present invention, and not to limit the protection scope of the present invention. All equivalent changes and modifications made according to the spirit of the present invention should be covered within the protection scope of the present invention.

The endpoints of the ranges and any values disclosed herein are not limited to the precise range or value, and such ranges or values should be understood to encompass values close to those ranges or values. For ranges of values, between the endpoints of each of the ranges and the individual points, and between the individual points may be combined with each other to give one or more new ranges of values, and these ranges of values should be considered as specifically disclosed herein.