DESC:FIELD
The present disclosure relates to a process for preparing crystalline pinoxaden.
DEFINITIONS
As used in the present disclosure, the following terms are generally intended to have the meaning as set forth below, except to the extent that the context in which they are used indicates otherwise.
Crystallization: The term “Crystallization” refers to the precipitation of a solid material (a precipitate), which includes a crystalline material, from a liquid solution of the solid material.
Herbicide: The term “Herbicide” refers to a chemical substance that inhibits and/or kills unwanted plants, such as sedges, weeds, grasses, and broadleaf plants, and that can be used for crop protection.
BACKGROUND
The background information herein below relates to the present disclosure but is not necessarily prior art.
Phenylpyrazoline based herbicide, 8-(2,6-diethyl-p-tolyl)-1,2,4,5-tetrahydro-7-oxo-7H-pyrazolo[1,2-d][1,4,5]oxadiazepin-9-yl-2,2-dimethylpropionate, is commonly known as Pinoxaden. On its application to weeds and unwanted plants, Pinoxaden is absorbed through leaves and then transmitted to the meristematic tissue. Pinoxaden is known to inhibit acetyl-CoA carboxylase (ACC) in the weeds and unwanted plants, thereby blocking fatty acid synthesis, hindering cell division, resulting in destruction of the cell membrane lipid structure, and leading to weed death. Pinoxaden acts systemically and at a fast speed, leading to growth inhibition of sensitive weeds within 48 hours after application. When pinoxaden is applied to leaves of the weed, the leaves start yellowing in 1 to 2 weeks, and lead to death of the weed within 3 to 4 weeks.
However, pinoxaden obtained by the conventional methods has low purity and its purification process is cumbersome, time consuming and not environmentally friendly.
There is, therefore, felt a need for providing a process for preparing crystalline pinoxaden that mitigates the drawbacks mentioned hereinabove.
OBJECTS
Some of the objects of the present disclosure, which at least one embodiment herein satisfies, are as follows:
It is an object of the present disclosure to ameliorate one or more problems of the prior art or to at least provide a useful alternative.
Another object of the present disclosure is to provide a process for preparing crystalline pinoxaden.
Yet another object of the present disclosure is to provide a crystalline pinoxaden having relatively high purity and in high yields.
Other objects and advantages of the present disclosure will be more apparent from the following description, which is not intended to limit the scope of the present disclosure.
SUMMARY
The present disclosure provides a process for crystallization of pinoxaden. The process comprises dissolving pinoxaden in a fluid medium under stirring, at a temperature in the range of 30 to 75 °C to obtain a solution comprising pinoxaden, which is allowed to cool to a temperature in the range of 10-25 °C, over a time period in the range of 5 to 12 hours to obtain a slurry comprising crystals of pinoxaden form G. The crystalline pinoxaden form G is isolated from the slurry. The crystalline pinoxaden form G has a purity in the range of 95% to 99.8%.
Pinoxaden used for crystallization is in any form of pinoxaden other than pinoxaden form G.
The fluid medium is at least one selected from the group consisting of methanol, ethylene dichloride (EDC), acetone, isopropyl alcohol, cyclohexane, o-xylene, p-xylene and m-xylene.
The weight ratio of pinoxaden to the fluid medium is in the range of 1:1 to 1:3.
BRIEF DESCRIPTION OF THE ACCOMPANYING DRAWING
The present disclosure will now be described with the help of the accompanying drawing, in which:
Figure 1 illustrates an X-ray powder diffractogram (X-RPD) of crystalline pinoxaden form G;
Figure 2 illustrates a differential scanning calorimetry (DSC) thermogram of crystalline pinoxaden form G, crystallized from xylene;
Figure 3 illustrates a differential scanning calorimetry (DSC) thermogram of crystalline pinoxaden form G, crystallized from methanol; and
Figure 4 illustrates a Fourier-transform infrared (FTIR) spectrum of crystalline pinoxaden form G, crystallized from xylene.

DETAILED DESCRIPTION
Embodiments, of the present disclosure, will now be described with reference to the accompanying drawing.
Embodiments are provided so as to thoroughly and fully convey the scope of the present disclosure to the person skilled in the art. Numerous details, are set forth, relating to specific components, and methods, to provide a complete understanding of embodiments of the present disclosure. It will be apparent to the person skilled in the art that the details provided in the embodiments should not be construed to limit the scope of the present disclosure. In some embodiments, well-known processes, well-known apparatus structures, and well-known techniques are not described in detail.
The terminology used, in the present disclosure, is only for the purpose of explaining a particular embodiment and such terminology shall not be considered to limit the scope of the present disclosure. As used in the present disclosure, the forms "a,” "an," and "the" may be intended to include the plural forms as well, unless the context clearly suggests otherwise. The terms "comprises," "comprising," “including,” and “having,” are open ended transitional phrases and therefore specify the presence of stated features, integers, steps, operations, elements, modules, units and/or components, but do not forbid the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof. The particular order of steps disclosed in the method and process of the present disclosure is not to be construed as necessarily requiring their performance as described or illustrated. It is also to be understood that additional or alternative steps may be employed.
The terms first, second, third, etc., should not be construed to limit the scope of the present disclosure as the aforementioned terms may be only used to distinguish one element, component, region, layer or section from another component, region, layer or section. Terms such as first, second, third etc., when used herein do not imply a specific sequence or order unless clearly suggested by the present disclosure.
Pinoxaden is a phenylpyrazoline based herbicide. Pinoxaden is known to inhibit acetyl-CoA carboxylase (ACC) in the weeds and unwanted plants, thereby blocking fatty acid synthesis. Pinoxaden acts systemically and at a fast speed, leading to death of sensitive weeds within 48 hours after application. Pinoxaden is represented by a following structure

Chemical Name: 8-(2,6-diethyl-p-tolyl)-1,2,4,5-tetrahydro-7-oxo-7H-pyrazolo[1,2-d][1,4,5]oxadiazepin-9-yl-2,2-dimethylpropionate
CAS no.: 243973-20-8
The present disclosure provides a simple and efficient process for preparing crystalline pinoxaden having a relatively high purity and in high yields.
In the present disclosure, the crystalline form of 8-(2,6-diethyl-p-tolyl)-1,2,4,5-tetrahydro-7-oxo-7H-pyrazolo[1,2-d][1,4,5]oxadiazepin-9-yl-2,2-dimethylpropionate, is referred to as “crystalline pinoxaden form G”.
The process of the present disclosure is described in details herein below:
Pinoxaden is crystallized by dissolving pinoxaden in a fluid medium under stirring, at a temperature in the range of 30 to 75 °C to obtain a solution comprising pinoxaden, which is allowed to cool to a temperature in the range of 10-25 oC over a time period in the range of 5 to 12 hours to obtain a slurry comprising crystals of pinoxaden form G. The crystalline pinoxaden form G is isolated from the slurry. The crystalline pinoxaden form G has a purity in the range of 95% to 99.8%.
In accordance with the embodiments of the present disclosure, pinoxaden used for crystallization is in any form of pinoxaden other than pinoxaden form G.
The fluid medium is at least one selected from the group consisting of methanol, ethylene dichloride (EDC), acetone, isopropyl alcohol, cyclohexane, o-xylene, p-xylene, and m-xylene.
In an exemplary embodiment of the present disclosure, the fluid medium is o-xylene. In another exemplary embodiment of the present disclosure, the fluid medium is methanol.
The weight ratio of pinoxaden to the fluid medium is in the range from 1:1 to 1:3. In accordance with an exemplary embodiment of the present disclosure, the weight ratio of pinoxaden to fluid medium is 1:2.
In accordance with the present disclosure, the crystallization of pinoxaden is carried out at a temperature in the range of 30 to 75 °C.
In accordance with one embodiment of the present disclosure, wherein o-xylene is used as a fluid medium for crystallization, the solution of pinoxaden in o-xylene is heated at 68 °C to obtain a clear solution comprising Pinoxaden, followed by cooling to obtain slurry comprising crystals of pinoxaden form G.
In accordance with another embodiment of the present disclosure, wherein methanol is used as a fluid medium for crystallization, the solution of pinoxaden in methanol is heated at 40 °C to obtain a clear solution comprising Pinoxaden, followed by cooling to obtain slurry comprising crystals of pinoxaden form G.
The slurry comprising crystals of pinoxaden form G is filtered to obtain a wet crystalline pinoxaden form G that is dried under reduced pressure to obtain a dried crystalline pinoxaden form G.
In the process of the present disclosure, isolation of the crystalline pinoxaden form G is achieved by a simple physical process such as filtration. Therefore, the process of the present disclosure is cost effective.
In accordance with one embodiment of the present disclosure, the dried crystalline pinoxaden form G has a purity of 99.728%.
In accordance with another embodiment of the present disclosure, the dried crystalline pinoxaden form G has a purity of 99.488%.
In accordance with one embodiment of the present disclosure, the crystalline pinoxaden form G, crystallized using o-xylene, exhibits an endothermic melting peak having a maximum at 123.39 °C in its differential scanning calorimetry (DSC) thermogram as represented in Figure 2.
In accordance with another embodiment of the present disclosure, the crystalline pinoxaden form G, crystallized using methanol, exhibits two endothermic melting peaks having maxima at 122.66 °C and 131.16 °C in its differential scanning calorimetry (DSC) thermogram as represented in Figure 3.

The present disclosure provides crystalline pinoxaden form G, which is polymorphic form of pinoxaden and exhibits at least 3 of the following peaks;
Xylene treatment
2- theta I/Io
5.59 100
9.58 39
9.78 71
11.05 85
12.58 68
13.64 20
14.49 15
15.76 21
16.03 23
16.26 20
17.01 44
18 17
18.84 14
19.57 29
20.55 15
21.01 31
21.39 25
21.9 23
23.38 12
23.6 13
25.03 11
25.25 25
25.58 32
28.11 39
29.66 15
31.76 20

in any combination, as 2? ± 0.2 degree in an X-ray powder diffractogram (X-RPD) recorded using Cu-Ka radiation at 25 °C, Figure 1.
In the present disclosure, the crystalline pinoxadene form G crystallized from o-xylene, is characterized by Fourier-transform infrared spectrum as represented in Figure 4.
The crystalline pinoxaden form G of the present disclosure can be used as herbicidal or in a herbicidal composition in the form of water dispersible granules, wettable powder, a suspension concentrate, an oil suspension, suspoemulsion and a capsule suspension.
The crystalline pinoxaden form G of the present disclosure can be included in herbicidal compositions or formulations in a suitable manner known in the art using auxiliaries, carriers and solvents and the like, in a known manner analogous to that for pinoxaden.
The disclosed crystalline pinoxaden form G has enhanced herbicidal activity as well as enhanced biocidal activity in controlling unwanted plant growth.
It is observed that the crystalline pinoxaden form G of the present disclosure is stable and shows enhanced efficacy when used as a herbicide or in a herbicidal composition.
The foregoing description of the embodiments has been provided for purposes of illustration and not intended to limit the scope of the present disclosure. Individual components of a particular embodiment are generally not limited to that particular embodiment, but, are interchangeable. Such variations are not to be regarded as a departure from the present disclosure, and all such modifications are considered to be within the scope of the present disclosure.
The present disclosure is further described in light of the following experiments which are set forth for illustration purpose only and not to be construed for limiting the scope of the disclosure. The following experiments can be scaled up to industrial/commercial scale and the results obtained can be extrapolated to industrial scale.
EXPERIMENTAL DETAILS
EXAMPLE 1: Crystallization of Pinoxaden from o-xylene
Pinoxaden (5 g) was dissolved in o-xylene (10 ml) under stirring, at 68 °C to obtain a clear solution, which was allowed to cool to 25 °C, over 12 hours to obtain a slurry comprising crystals of Pinoxaden form G. The crystalline pinoxaden form G was isolated by filtering the slurry and drying at 30 °C. The crystalline pinoxaden form G has a purity of 99.728%.
EXAMPLE 2: Crystallization of Pinoxaden from methanol
Pinoxaden (5 g) was dissolved in methanol (10 ml) under stirring, at 40 °C to obtain a clear solution, which was allowed to cool to 25 °C, over 12 hours to obtain a slurry comprising crystals of Pinoxaden form G. The crystalline pinoxaden form G was isolated by filtering the slurry and drying at 30 °C. The crystalline pinoxaden form G has a purity of 99.488%.
Similarly, pinoxaden was crystallized from various solvents as described in Table 1.

Table 1: Crystallization of pinoxaden form G using various solvents
Starting Pinoxaden Crystallization Pinoxaden form G
No. Wt (g) Purity (%) mp (°C) by DSC Solvent used Procedure Yield (g) Purity (%) mp (°C) by DSC
1 5 g 98.92 122.5
(-64.28 j/g) Methanol Mixed pinoxaden (5 g) in methanol (10 ml) at 40 °C, clear liquid was kept overnight and filtered at 30 °C. 2.22 99.488 122.66 °C
(-47.44 j/g)
and
131.16 °C
(-50.93 j/g)
2 5 g 98.92 122.5
(-64.28 j/g) Ethylene dichloride (EDC) Mixed pinoxaden (5 g) in EDC (5 ml) at 38 °C, clear liquid was kept overnight and filtered at 30 °C. 0.24 98.002 122.07 °C
(-49.02 j/g) and
130.23 °C
(-46.76 j/g)
3 5 g 98.92 122.5
(-64.28 j/g) Acetone Mixed pinoxaden (5 g) in acetone (10 ml) at 40 °C, clear liquid was kept overnight and filtered at 30 °C. 2.21 99.646 123.34 °C
(-68.88 j/g) and
131.61 °C
(-0.15 j/g)
4 5 g 98.92 122.5
(-64.28 j/g) Isopropyl alcohol Mixed pinoxaden (5 g) in isopropyl alcohol (10 ml) at 46 °C, clear liquid was kept overnight and filtered at 30 °C. 4.7 98.843 122.84 °C
(-70.22 j/g)
5 5 g 98.92 122.5
(-64.28 j/g) Cyclohexane Mixed pinoxaden (5 g) in cyclohexane (75 ml) at 65 °C, clear liquid was kept overnight and filtered at 30 °C. 4.1 99.648 123.34 °C
(-61.38 j/g)
6 5 g 98.92 122.5
(-64.28 j/g) Molten Pinoxaden (140 °C) Pinoxaden (5 g) was heated at 140 °C to melt and poured on a petri dish to solidify and then powdered. 5 97.214 121.75 °C
(-42.17 j/g) and
129.91 °C
(-24.03 j/g)
7 5 g 98.92 122.5 (-64.28 j/g) o-Xylene Mixed pinoxaden (5 g) o-xylene (10 ml) at 68 °C, Clear liquid was kept overnight and filtered at 30 °C 3.8 99.728 123.39 °C
(-75.57 j/g) and
131.58 °C
(-0.05 j/g)

Table 2: 2? values of Crystalline pinoxaden form G, recorded in an X-ray powder diffractogram (X-RPD)
Xylene treatment
2- theta I/Io
5.59 100
9.58 39
9.78 71
11.05 85
12.58 68
13.64 20
14.49 15
15.76 21
16.03 23
16.26 20
17.01 44
18 17
18.84 14
19.57 29
20.55 15
21.01 31
21.39 25
21.9 23
23.38 12
23.6 13
25.03 11
25.25 25
25.58 32
28.11 39
29.66 15
31.76 20

TECHNICAL ADVANCEMENTS
The present disclosure described herein above has several technical advantages including, but not limited to, the realization of:
- a simple and environmental friendly process for preparing crystalline pinoxaden; and
- crystalline pinoxaden having relatively high purity and in high yields.
Throughout this specification the word “comprise”, or variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.
The use of the expression “at least” or “at least one” suggests the use of one or more elements or ingredients or quantities, as the use may be in the embodiment of the invention to achieve one or more of the desired objects or results. While certain embodiments of the inventions have been described, these embodiments have been presented by way of example only, and are not intended to limit the scope of the inventions. Variations or modifications to the formulation of this invention, within the scope of the invention, may occur to those skilled in the art upon reviewing the disclosure herein. Such variations or modifications are well within the spirit of this invention.
The numerical values given for various physical parameters, dimensions and quantities are only approximate values and it is envisaged that the values higher than the numerical value assigned to the physical parameters, dimensions and quantities fall within the scope of the invention unless there is a statement in the specification to the contrary.
While considerable emphasis has been placed herein on the specific features of the preferred embodiment, it will be appreciated that many additional features can be added and that many changes can be made in the preferred embodiment without departing from the principles of the disclosure. These and other changes in the preferred embodiment of the disclosure will be apparent to those skilled in the art from the disclosure herein, whereby it is to be distinctly understood that the foregoing descriptive matter is to be interpreted merely as illustrative of the disclosure and not as a limitation.
,CLAIMS:WE CLAIM:
1. A process for preparing crystalline pinoxaden, said process comprising the following steps:
a) dissolving pinoxaden in a fluid medium under stirring, at a temperature in the range of 30 to 75 °C to obtain a solution comprising pinoxaden;
b) crystallizing pinoxaden in said solution, by cooling said solution to a temperature in the range of 10 to 25 °C, over a time period in the range of 5 to 12 hours to obtain a slurry comprising crystals of pinoxaden form G; and
c) isolating said crystalline pinoxaden form G from the slurry;
wherein said crystalline pinoxaden form G has purity in the range of 95% to 99.8%.
2. The process as claimed in claim 1, wherein said pinoxaden used for dissolving in the fluid medium, is in any form of pinoxaden other than pinoxaden form G.
3. The process as claimed in claim 1, wherein said fluid medium is at least one selected from the group consisting of methanol, ethylene dichloride (EDC), acetone, isopropyl alcohol, cyclohexane, o-xylene, p-xylene and m-xylene.
4. The process as claimed in claim 1, wherein the weight ratio of pinoxaden to the fluid medium is in the range from 1:1 to 1:3.
5. The process as claimed in claim 1, wherein the slurry comprising crystals of pinoxaden form G is filtered to obtain wet crystalline pinoxaden form G that is dried under reduced pressure to obtain dried crystalline pinoxaden form G.
6. The process as claimed in claim 1, wherein said crystalline pinoxaden form G, on being crystallized using methanol, exhibits two endothermic melting peaks having maxima at 122.66 °C and 131.16 °C in its differential scanning calorimetry (DSC) thermogram