阅读说明：本技术 制备可灭踪的工艺、其新颖形式及其用途 (Process for the preparation of clomazone, novel forms thereof and uses thereof ) 是由 J·T·布里斯托 于 2014-06-30 设计创作，主要内容包括：本发明提供一种制备可灭踪的工艺,该方法包括在碱存在下,于水性介质中使4,4-二甲基-3-异噁唑酮与2-氯芐基氯反应。本发明亦揭示一种制备可灭踪的方法,该方法包括(a)于有机溶剂中从溶液形成可灭踪结晶；及(b)分离出所得结晶。N-苯尤其适合用作溶剂。此外,本发明提供第I型2-[(2-氯苯基)甲基]-4,4-二甲基-3-异噁唑酮(可灭踪)晶体,其中第I型多晶体具有以下最少一种特性：(i)X光粉末衍射谱图的特征峰以2θ(+/-0.20°θ)列示,位于下列一个或多个位置：约10.63、16.07、18.08、19.11、19.34、21.20、24.78及28.80；及(ii)红外线光谱图的特征峰位于：约2967及2870cm<Sup>-1</Sup>。(The present invention provides a process for the preparation of clomazone comprising reacting 4, 4-dimethyl-3-isoxazolone with 2-chlorobenzyl chloride in an aqueous medium in the presence of a base. Also disclosed is a process for the preparation of clomazone, which process comprises (a) forming clomazone crystals from a solution in an organic solvent; and (b) isolating the crystals obtained. N-benzene is particularly suitable as solvent. In addition, the present invention provides form I of 2- [ (2-chlorophenyl) methyl]-4, 4-dimethyl-3-isoxazolone (clomazone) crystals, wherein polymorph form I has at least one of the following properties: (i) x-rayThe characteristic peaks of the powder diffraction pattern, listed in 2 θ (+/-0.20 ° θ), are located at one or more of the following positions: about 10.63, 16.07, 18.08, 19.11, 19.34, 21.20, 24.78, and 28.80; and (ii) the characteristic peaks of the infrared spectrogram are located as follows: about 2967 and 2870cm ‑1 。)

1. A process for the preparation of clomazone, which process comprises:

4, 4-dimethyl-3-isoxazolone 2-chlorobenzyl chloride is reacted in an aqueous medium in the presence of a first base.

2. The process according to claim 1, wherein the base is selected from the group consisting of hydroxides, carbonates, hydrides or mixtures thereof.

3. The process according to any one of the preceding claims, wherein the base is a metal base.

4. The process according to claim 3, wherein the metal is an alkali metal or an alkaline earth metal.

5. The process according to claim 4, wherein the metal is sodium or potassium.

6. The process of any one of the preceding claims, wherein the pH of the reaction mixture is between 7.5 and 9.5.

7. The process according to claim 6, wherein the pH is between 8.5 and 9.5.

8. The process of any one of the preceding claims, wherein the reaction is carried out at elevated temperature.

9. The process according to claim 8, wherein the reaction is carried out at a temperature between 50 and 95 ℃.

10. The process according to claim 9, wherein the reaction is carried out at a temperature between 60 and 90 ℃.

11. The process according to any of the preceding claims, wherein 3-chloro-N-hydroxy-2, 2-dimethylpropionamide is cyclized using a second base to produce 4, 4-dimethyl-3-isoxazolone containing 2-chlorobenzyl chloride.

12. The process according to claim 11, wherein the cyclization reaction is carried out in the presence of a solvent.

13. The process according to claim 12, wherein the solvent is water.

14. A process according to any one of claims 11 to 13, wherein the second base is selected from a hydroxide, a carbonate, a hydride or a mixture thereof.

15. The process of any one of claims 11 to 14, wherein the second base is a metal base.

16. The process according to claim 15, wherein the metal is an alkali metal or an alkaline earth metal.

17. The process according to claim 16, wherein the metal is sodium or potassium.

18. The process according to any one of claims 11 to 17, wherein the pH of the reaction mixture is between 7.5 and 9.5.

19. The method of any one of claims 11 to 18, wherein the reaction is carried out at an elevated temperature.

20. The process according to claim 19, wherein the reaction is carried out at a temperature between 20 and 60 ℃.

21. The process according to claim 20, wherein the reaction is carried out at a temperature between 30 and 50 ℃.

22. The process of any one of claims 11 to 21, wherein

3-chloro-N-hydroxy-2, 2-dimethylpropionamide is prepared via the reaction of 3-chloro-2, 2-dimethylpropionyl chloride with hydroxylamine hydrochloride in the presence of a third base.

23. The process according to claim 22, wherein the reaction is carried out in the presence of a solvent.

24. The process according to claim 23, wherein the solvent is water.

25. The process according to any one of claims 22 to 24, wherein the third base is selected from the group consisting of hydroxides, carbonates, hydrides or mixtures thereof.

26. The process according to any one of claims 22 to 25, wherein the third base is a metal base.

27. The process according to claim 26, wherein the metal is an alkali metal or an alkaline earth metal.

28. The process according to claim 27, wherein the metal is sodium or potassium.

29. The process of any one of claims 22 to 28, wherein the pH of the reaction mixture is between 7.0 and 9.5.

30. The process according to any one of claims 22 to 29, wherein the reaction is carried out at elevated temperature.

31. The process according to claim 30, wherein the reaction is carried out at a temperature between 50 and 95 ℃.

32. Process according to claim 31, characterized in that the reaction is carried out at a temperature between 60 and 90 ℃.

33. A method of preparing clomazone:

(a) forming a clomazone crystal from the solution in an organic solvent; and

(b) the resulting crystals were isolated.

34. The method according to claim 33, wherein the solvent is non-polar.

35. The process according to claim 33 or 34, wherein the solvent is selected from the group consisting of carboxamides, benzene and substituted benzene derivatives, nitriles, haloalkanes, alkanes and mixtures thereof.

36. The method according to claim 35, wherein the solvent is selected from the group consisting of dimethylformamide, benzene, toluene, acetonitrile, dichloromethane, hexane, and mixtures thereof.

37. The method according to any one of claims 33 to 36, wherein the solvent is n-hexane.

38. A form I crystal of 2- [ (2-chlorophenyl) methyl ] -4, 4-dimethyl-3-isoxazolone (clomazone), characterized by at least one of the following properties:

(i) the characteristic peaks of the X-ray powder diffraction pattern are listed in terms of 2 theta (+/-0.20 DEG theta) and are located at one or more of the following positions: about 10.63, 16.07, 18.08, 19.11, 19.34, 21.20, 24.78, and 28.80; and

(ii) the characteristic peaks of the Infrared (IR) spectrum are located: about 2967 and 2870cm^-1。

39. A method of controlling plant growth at a locus, the method comprising applying to the locus a formulation comprising clomazone or form I clomazone prepared by the process of claims 1 to 32 or the method of claims 33 to 37.

40. Use of clomazone or form I clomazone prepared by the process of claims 1 to 32 or the method of claims 33 to 37 for controlling plant growth.

41. A process for the preparation of clomazone substantially as hereinbefore described.

42. A process for the preparation of clomazone by crystallisation techniques substantially as hereinbefore described.

[ technical field ] A method for producing a semiconductor device

The invention relates to an agricultural herbicide 2- [ (2-chlorphenyl) methyl ] -4, 4-dimethyl-3-isoxazolone (2- [ (2-chlorophenyl) methyl ] -4,4-dimethyl-3-isoxazolidinone, clomazone). The present invention relates in particular to novel crystalline polymorphs of clomazone, processes for their preparation and compositions containing them.

[ Prior Art ]

2- [ (2-chlorophenyl) methyl ] -4, 4-dimethyl-3-isoxazolone, a compound of the generic name + -clomazone, is disclosed in US 4,405,357, including describing its herbicidal properties. The herbicidal isoxazolone has the following chemical structural formula (I):

US 4,405,357 discloses a process for the preparation of clomazone. Therein is disclosed the following process for the synthesis of clomazone:

US 4,405,357 discloses another method, as follows:

however, these methods produce the desired product in relatively low yields due to the production of by-products during the process. The by-product chemical formulas (II) and (III) are as follows:

and

US 4,742,176 discloses that a typical product mixture obtained by the above process contains compounds of formulae (I), (II) and (III), wherein formula (I): (II): the ratio of (III) is about 85/10/5. It would be useful to have an improved process that increases the amount of the clomazone produced and reduces the production of by-products of formulas (II) and (III).

Furthermore, the process of US 4,405,357 has several disadvantages. As mentioned above, methanol (MeOH) and Dimethylformamide (DMF) were used as solvents during the reaction. However, the use of the above-mentioned solvents causes various problems, particularly on a commercial production scale. For example, methanol is a hazardous solvent that is flammable, has a low ignition point, and also produces peroxides. Therefore, the use of methanol is very limited in large-scale production. In addition, aprotic polar solvents such as Dimethylformamide (DMF) are water soluble and can generally be recovered as an azeotrope containing large amounts of water.

US 4,742,176 discloses an improvement to the second method of US 4,405,357. Wherein, the process is changed into that before the required product is separated, the product mixture is firstly contacted with hydrogen chloride gas. This treatment converts the compound of formula (II) into a mixture of 4, 4-dimethyl-3-isoxazolone and 2-chlorobenzyl chloride, which can be made into the desired product using a base. The compound of formula (III) in the product is converted to other components upon contact with hydrogen chloride and can be easily separated. Hydrogen chloride does not have any effect on the amount of clomazone. However, these improvements result in a more complex process involving the use of additional components, particularly hydrogen chloride gas, which is undesirable.

However, there is no simple synthetic method for producing a desired product in a large amount with high purity.

Therefore, there is an urgent and practical need in the art for efficient methods of preparing and purifying a clomazone that address the drawbacks and deficiencies of the inherent methods.

In addition, no known crystalline polymorph is currently known to be ablated (crystalloid polymorphic forms).

[ summary of the invention ]

An improved process for the preparation of clomazone which eliminates the use of solvents as in the above-described intrinsic processes, reduces the production of by-products, thereby eliminating the need for extensive purification procedures and increasing the production of clomazone. The method is particularly suitable for the commercial production of clomazone.

A first aspect of the invention provides a method of modulating a vanishing trace, the method comprising:

4, 4-dimethyl-3-isoxazolone is reacted with 2-chlorobenzyl chloride in an aqueous medium containing a base.

It has been unexpectedly found that the reaction of 4, 4-dimethyl-3-isoxazolone with 2-chlorobenzyl chloride in a base containing water as the solvent produces a high yield of clomazone. The use of water as a solvent is far superior to known methods and does not require the use of solvents such as methanol and dimethylformamide. The process produces a high purity clomazone without the need for extensive separation procedures on the product mixture. In particular, the clomazone can be obtained from the reaction mixture by simple crystallization techniques.

4, 4-dimethyl-3-isoxazolone is reacted with 2-chlorobenzyl chloride in an aqueous medium containing a base. Suitable bases include one or a mixture of hydroxides, carbonates and hydrides. Suitable bases include metal and ammonium compounds, with metal compounds being preferred, especially alkali and alkaline earth metal basic compounds. Alkali metal basic compounds are particularly preferred. The base is preferably a carbonate or hydroxide, and the basic compound is preferably an alkali metal carbonate or hydroxide. Sodium and potassium are preferred among the alkali metals. Sodium hydroxide and potassium hydroxide are preferred bases. Sodium carbonate and potassium carbonate are particularly preferred bases.

4, 4-dimethyl-3-isoxazolone is reacted with 2-chlorobenzyl chloride in an alkaline environment. It is recommended that the pH of the reaction mixture be between 7.5 and 9.5, more preferably between 8.5 and 9.5.

The reaction process is as follows:

it is advisable to heat the reaction mixture. Suitable temperatures are between 50 and 95 ℃, preferably 60 to 90 ℃. About 85 ℃ was found to be a very suitable reaction temperature.

Cyclization of 3-chloro-N-hydroxy-2, 2-dimethylpropionamide using bases can form 4, 4-dimethyl-3-isoxazolone. Suitable bases are as described above. Likewise, alkali metal hydroxides are preferred bases, especially sodium hydroxide. It is particularly proposed to cyclize 3-chloro-N-hydroxy-2, 2-dimethylpropionamide in a solvent containing a base, especially an aqueous medium in which water is used as solvent.

Cyclizing 3-chloro-N-hydroxy-2, 2-dimethylpropionamide under alkaline environment. The pH of the reaction mixture is preferably from 7.5 to 9.5.

The reaction process is as follows:

the reaction mixture is preferably heated. Suitable temperatures are between 20 and 60 ℃ and preferably between 30 and 50 ℃. About 45 ℃ was found to be a very suitable reaction temperature.

Hydroxylamine hydrochloride (NH)₂Oh, hcl) with 3-chloro-2, 2-dimethylpropionyl chloride under alkali-containing conditions to form 3-chloro-N-hydroxy-2, 2-dimethylpropionamide. Suitable bases are as described above. Likewise, alkali metal hydroxides are preferred bases, especially sodium hydroxide. It is particularly recommended that the reaction of 3-chloro-2, 2-dimethylpropionyl chloride with hydroxylamine hydrochloride base is carried out in a solvent, especially an aqueous medium using water as solvent.

The reaction of 3-chloro-2, 2-dimethylpropionyl chloride with hydroxylamine hydrochloride is carried out under alkaline conditions. The pH of the reaction mixture is preferably from 7.0 to 9.5, preferably from 7.0 to 8.5, more preferably from 7.0 to 7.5.

The reaction process is as follows:

it is advisable to heat the reaction mixture. Suitable temperatures are between 50 and 95 ℃ and preferably between 60 and 90 ℃. It was found that about 85 ℃ is very suitable for carrying out the reaction.

The advantage of the preparation of clomazone from 3-chloro-2, 2-dimethylpropionyl chloride in the above reaction process is that all steps of the reaction process are carried out in an aqueous medium with water as solvent, especially in respect of the base used. An additional advantage is that the same base can be used throughout the above reaction.

As mentioned above, this method mentioned above can produce a high yield of the clomazone, with small amounts of by-products being produced. Thus, the simple crystallization procedure allows the extraction of clomazone from the reaction mixture, eliminating the need for complex separation and purification techniques.

Further, the present invention provides a method for preparing clomazone, which comprises:

(a) forming a vanishing crystal from the solution using an organic solvent; and

(b) the resulting crystals were isolated.

Clomazone is practically insoluble in water, but soluble in a variety of organic solvents. In the process of the present invention, after crystallization from solution using an organic solvent, the clomazone crystals can be isolated. The method can use a single solvent or a mixture of organic solvents. It is recommended that the organic solvent is selected from the group consisting of carboxamides (e.g. dimethylformamide), benzene and substituted benzene derivatives (e.g. toluene), nitriles (e.g. acetonitrile), haloalkanes (e.g. dichloromethane), alkanes (e.g. hexane, especially n-hexane) and mixtures thereof. It is recommended that the solvent be non-polar. Among them, the nonpolar solvent is preferably an alkane, and aliphatic alkanes (aliphatic alkanes) are preferable, especially normal and straight-chain alkanes. In the process of this aspect of the invention, it is particularly preferred that the solvent used is an alkane containing from six to ten carbon atoms, preferably from six to eight carbon atoms, especially hexane, especially n-hexane.

In the method of the present invention, the clomazone is dissolved in an organic solvent, and preferably heated. The resulting solution is cooled to form the clomazone crystals and the crystalline product is separated from the organic solvent. Techniques and equipment for preparing clomazone solutions in organic solvents, forming clomazone crystals and isolating the crystalline product are well known in the art and commercially available.

In the process of the first aspect of the invention, the amount of clomazone is dissolved in an organic solvent and the solution obtained is treated in the process of the second aspect of the invention to isolate the clomazone in the final reaction medium.

Surprisingly, it has been found that the above-described crystallization process produces a novel form of polycrystalline crystal, hereinafter referred to as "form I".

Accordingly, the present invention further provides crystalline 2- [ (2-chlorophenyl) methyl ] -4, 4-dimethyl-3-isoxazolone (clomazone) form I, wherein the form I polymorph has at least one of the following properties:

(i) the characteristic peaks of the X-ray powder diffraction pattern are listed in terms of 2 theta (+/-0.20 DEG theta) and are located at one or more of the following positions: about 10.63, 16.07, 18.08, 19.11, 19.34, 21.20, 24.78, and 28.80; and

(ii) the characteristic peaks of the Infrared (IR) spectrum are located: about 2967 and 2870cm^-1。

Fig. 1 shows an X-ray powder diffraction pattern of crystalline polymorph form I. As can be seen, in the X-ray powder diffraction pattern of form I, the characteristic peaks (listed in 2 θ (+/-0.20 ° θ)) are located at one or more of the following positions: 10.63, 16.07, 18.08, 19.11, 19.34, 21.20, 24.78 and 28.80.

FIG. 2 shows the Infrared (IR) spectrum of form I. As can be seen, the type I infrared spectrum has a range of 3000cm^-1The characteristic peaks are located at about 2967 and 2870cm^-1。

As mentioned above, form I clomazone may be prepared as described above. Wherein the clomazone is prepared by crystallizing clomazone from a solution using an organic solvent, preferably hexane, acetonitrile, dichloromethane, dimethylformamide, toluene and mixtures thereof.

The clomazone and clomazone I prepared by the process and method of the present invention are useful as herbicides for controlling the growth of unwanted plants. The use of vanishing trace to control plant growth is well known in the art.

In addition, another aspect of the present invention provides a method for controlling plant growth at a locus (locus). The method comprises the clomazone or form I clomazone prepared by the process and method described above.

Another aspect of the present invention provides a method of controlling plant growth using the clomazone or form I clomazone prepared by the process and method described above.

The form I clomazone crystals may be used in one formulation form or other forms prepared therefrom. For example, the clomazone I can be prepared as a direct spray solution, powder, suspension or dispersion, emulsion, oil dispersion, paste, dustable product, broadcast material or granule, for use by spraying, misting, sprinkling, broadcasting or pouring. The form of use depends entirely on the use, in particular in order to ensure the most homogeneous distribution of the active compounds according to the invention in each case.

Aqueous forms can be prepared by adding water to emulsion concentrates, pastes or wettable powders (sprayable powders, oil dispersions). The material can be homogenized in water directly (or pre-dissolved in oil or solvent) by wetting agent, tackifier, dispersant or emulsifier to make into emulsion, paste or oil dispersion. However, it is also possible to prepare concentrates comprising the active substance, wetting agent, viscosity enhancer, dispersant or emulsifier and, if appropriate, solvent or oil, and the concentrates concerned can be diluted with water.

In the available formulations, the concentration of the active compound varies considerably. Generally from 0.0001 to 10% by weight, preferably from 0.01 to 1% by weight.

The following are examples of formulations of the present vanishing products:

1. the product used will be diluted with water for foliar application. The formulation may also be used for seed (with or without dilution) for seed treatment applications.

A) Water soluble concentrate (SL, LS)

10 parts by weight of active compound are dissolved in 90 parts by weight of water or water-soluble solvent. Wetting agents or other auxiliaries may be selected instead. Upon dilution with water, the active compound dissolves, giving a formulation containing 10% (W/W) active compound.

B) Dispersion Concentrate (DC)

20 parts by weight of active compound are dissolved in 70 parts by weight of cyclohexanone and 10 parts by weight of a dispersant, for example polyvinylpyrrolidone, are added. Water was added to dilute the dispersion to give a formulation with 20% (w/w) active compound.

C) Emulsifiable Concentrates (EC)

15 parts by weight of active compound are dissolved in 80 parts by weight of xylene, and 5 parts by weight of calcium dodecylbenzenesulfonate and 5 parts by weight of castor oil ethoxylate are added in each case. Water was added to dilute the emulsion, resulting in a formulation with 15% (w/w) active compound.

D) Emulsion (EW, EO, ES)

25 parts by weight of active compound are dissolved in 35 parts by weight of xylene, and 5 parts by weight of calcium dodecylbenzenesulfonate and 5 parts by weight of castor oil ethoxylate are added in each case. The mixture is dissolved in 30 parts by weight of water using an emulsifying machine (e.g., Ultraturrax) and made into a homogeneous emulsion. Water was added to dilute the emulsion, resulting in a formulation with 25% (w/w) active compound.

E) Suspension (SC, OD, FS)

In a stirred ball mill, 10 parts by weight of dispersant, wetting agent and 70 parts by weight of water or an organic solvent are added, 20 parts by weight of active compound are ground and a fine active compound suspension is prepared. Water was added to dilute a stable suspension of active compound, resulting in a formulation with 20% (W/W) active compound.

F) Water dispersible granule and Water soluble granule (WG, SG)

50 parts by weight of dispersing agent and wetting agent are added, 50 parts by weight of active compound are finely ground and made into water-dispersible or water-soluble granules by means of technical instruments, for example extrusion devices, spray towers, fluidized beds. Water is added to dilute a stable active compound dispersion or solution, resulting in a formulation with 50% (W/W) active compound.

G) Water-dispersible powders and water-soluble powders (WP, SP, SS, WS)

25 parts by weight of dispersing agent, wetting agent and silica gel are added to a rotor-stator mill and 75 parts by weight of active compound are ground. Dilution with water to a stable dispersion or addition of the active compound, gives a (W/W) solution of the active compound with 75% of the formulation. Water is added to dilute a stable dispersion or solution of the active compound, resulting in a formulation with 75% (W/W) active compound.

H) Gel Formulations (GF) (for seed treatment purposes only)

In a stirred ball mill, 10 parts by weight of dispersant, 1 part by weight of gelling/wetting agent and 70 parts by weight of water or an organic solvent are added, 20 parts by weight of active compound are ground and a fine active compound suspension is prepared. Water was added to dilute a stable suspension of active compound, resulting in a formulation with 20% (W/W) active compound.

2. The product can be directly applied to the leaf surface without dilution. For seed treatment, the product concerned is diluted.

I) Powdering powder (DP, DS)

5 parts by weight of active compound are finely ground and 95 parts by weight of finely divided kaolin are homogeneously mixed. This formulation produced a pulverisable product with 5% (w/w) of the active compound.

J) Granules (GR, FG, GG, MG)

A formulation with 0.5% (W/W) active compound was made by finely grinding 0.5 parts by weight active compound and adding 95.5 parts by weight carrier. Current methods of making granules include extrusion, spray drying treatment or the use of a fluidized bed, and the granules thus made can be applied directly to the foliage without dilution.

K) Microcapsule (ME)

A formulation having 0.5% (W/W) active compound was made by finely grinding 0.5 parts by weight active compound and adding 95.5 parts by weight of a mixture of polyurea, crosslinker and carrier. This method provides a microcapsule product containing 5% (w/w) active compound wherein the active clomazone ingredient is encapsulated within a microcapsule having a polymeric shell.

L) microcapsule granules (MEG)

Finely grinding 0.5 parts by weight of active compound and adding 95.5 parts by weight of a mixture of polyurea, crosslinking agent and a solid carrier and a binder, and granulating the resulting mixture; the particles are coated with a composition comprising a binder and air dried. This process provides particles with 5% (w/w) active compound, which contain microencapsulated active ingredient.

[ description of the drawings ]

Fig. 1 shows an X-ray powder diffraction pattern of crystalline polymorph form I. As can be seen, in the X-ray powder diffraction pattern of form I, the characteristic peaks (listed in 2 θ (+/-0.20 ° θ)) are located at one or more of the following positions: 10.63, 16.07, 18.08, 19.11, 19.34, 21.20, 24.78 and 28.80.

FIG. 2 shows the Infrared (IR) spectrum of form I. As can be seen, the type I infrared spectrum has a range of 3000cm^-1The characteristic peaks are located at about 2967 and 2870cm^-1。

[ detailed description ] embodiments

The following specific examples illustrate specific embodiments of the invention.

Examples of the invention

Example 1: synthesis of clomazone

The method comprises the following steps: preparation of 3-chloro-N-hydroxy-2, 2-dimethylpropionamide (CNHP)

The general reaction for the preparation of 3-chloro-N-hydroxy-2, 2-dimethylpropionamide is as follows:

1200 kg of water are introduced into a 4000 l reactor, and 318 kg of hydroxylamine hydrochloride (NH2OH. HCl) are added. The resulting mixture was stirred at room temperature until the hydroxylamine hydrochloride was completely dissolved in the water. Within 1.5 hours, 50% aqueous sodium hydroxide solution was added dropwise to the reactor, the pH was adjusted to 7.0 to 7.5, and the temperature was maintained at 20 to 25 ℃. After the addition of the sodium hydroxide solution, 713 kg of 3-chloro-2, 2-dimethylpropionyl chloride were added dropwise to the reaction mixture over a further 3 hours. The reaction mixture was stirred at the above temperature until the reaction was complete.

The resulting mixture was cooled to 5 to 10 ℃, maintained at this temperature for 1.5 hours and stirred. The mixture was filtered to separate the solid material and the drying step was carried out under high vacuum. The crude product obtained was purified with acetone to give pure 3-chloro-N-hydroxy-2, 2-dimethylpropionamide (645 kg, purity: 98%, productivity: 92%).

Step two: preparation of 4, 4-dimethyl-3-isoxazolone (DIO)

The product obtained in step one is used to prepare 4, 4-dimethyl-3-isoxazolone, typically in the following reaction:

1000 kg of water are introduced into a 3000 l reactor, and 640 kg of 3-chloro-N-hydroxy-2, 2-dimethylpropionamide are added. The resulting solution was stirred at room temperature for one hour, and the temperature was allowed to rise to 45 ℃. A50% aqueous solution of sodium hydroxide was added dropwise to the mixture over 5 hours. The reaction mixture was stirred at room temperature until the reaction was complete.

The resulting solution was cooled to 5 to 10 ℃, maintained at this temperature over 3 hours and stirred. The mixture was filtered to separate the solid material. The solid was washed with water and subjected to a drying step in a high vacuum environment to form pure 4, 4-dimethyl-3-isoxazolone (about 466 kg, purity: 96%, productivity: 93%).

Step three: preparation of 2- (2-chlorobenzyl) -4, 4-dimethyl-1, 2-isoxazol-3-one (clomazone)

The product obtained in step two is used to prepare clomazone, generally in the following reaction:

1000 kg of water are introduced into a 4000 l reactor and 460 kg of 4, 4-dimethyl-3-isoxazolone are added. The resulting solution was stirred at room temperature for one hour and 383 kg of sodium carbonate were added little by little. The mixture was heated to 85 ℃, maintained at this temperature and stirred for 2 hours. 672 kg of 2-chlorobenzyl chloride are then added dropwise at 85 ℃ over a period of 5 hours. Then, the resulting solution was stirred at the same temperature until the reaction was completed.

The resulting mixture was cooled to room temperature, 800 kg of methylene chloride was added to the reactor, and stirred at room temperature for 15 hours. The aqueous phase was separated and extracted with dichloromethane (three times). The dichloromethane was withdrawn by distillation and 2000 kg of hexane was added to the reactor. The resulting mixture was refluxed for one hour, then cooled to 10 to 15 ℃, and stirred for an additional hour.

The solid material was filtered, washed several times with hexane, and then subjected to a drying step under high vacuum to form pure clomazone (815 kg, purity: 96%).

The results obtained using sodium hydroxide instead of sodium carbonate as base were similar.

Example 2: preparation of form I clomazone

2 g of clomazone was added to 10 g of hexane and heated until completely dissolved. The resulting solution was refluxed for one hour, then cooled to 10 to 15 ℃ and stirred for another hour. The reaction mixture was filtered and the solid was isolated. The solid was washed several times with hexane and then subjected to a drying step under high vacuum to form pure clomazone crystals (815 kg, purity: 96%).

The crystals were identified as type I knock-down by infrared and X-ray diffraction spectra.

FIG. I is a spectrum of type I extinct infrared rays with characteristic peaks at 2967 and 2870cm^-1。

The second graph is the X-ray powder diffraction pattern of the form I clomazone, and the emission data is listed in the following Table I.

Watch 1

The parameters of the X-ray diffraction spectrum are as follows:

wavelength of light

Specific wavelength type K α

1.540598

1.544426

Strength ratio of K α 2/K α 1: 0.50

1.541874

1.392250

Incident beam path

Radius (mm): 240.0

X-ray tube

Name: PW3373/10Cu LFF DK185240

Cathode material: cu

Voltage (kV): 40

Current (mA): 40

Focusing

Focusing type: line (Line)

Length (mm): 12.0

Breadth (mm): 0.4

Exit angle (°): 6.0

Soller slit

Name: soller 0.04rad.

Slit (rad.): 0.04

Shading frame

Name: mask Fixed 15mm (MPD/MRD)

Breadth (mm): 11.60

Anti-scattering slit

Name: slit Fixed 1/2 degree

Type (2): fixing

Height (mm): 0.76

Divergent slit

Name: slit Fixed 1 degree

Distance from sample (mm): 140

Type (2): fixing

Height (mm): 0.38

Diffracted beam path

Radius (mm): 240.0

Anti-scattering slit

Name: AS Slit 5.5mm (X' Celerator)

Type (2): fixing

Height (mm): 5.50

Filter

Name: nickel (II)

Thickness (mm): 0.020

Materials: ni

Detector

Name: x' Celerator

Type (2): RTMS detector

Mode (2): scanning

Effective length (°): 2.122

Origin of origin

The manufacturer: soochow University

Application software: x' Pert Data Collector vs. 2.1a

Instrument control software: XPERT-PRO vs. 1.6

Instrument numbering: 0000000026005495

Scanning axis: gonio

Scanning range (°): 3.0150-60.0004

Step size (°): 0.0334

Counting: 1705

Scanning mode: continuous

Example 3: preparation of form I clomazone

2 grams of clomazone prepared as described in example 1 and 10 grams of acetonitrile were heated until complete dissolution. The resulting mixture was refluxed for one hour, then cooled to 10 to 15 ℃ and stirred for another hour. The mixture was filtered and the solid was isolated. The solid was washed several times with acetonitrile and then subjected to a drying step under high vacuum to form pure clomazone crystals (815 kg, purity: 96%). These crystals were identified as type I knock-down by the infrared and X-ray diffraction spectra described in example 2.

Example 4: preparation of form I clomazone

2 grams of the clomazone prepared as described in example 1 was dissolved in 10 grams of methylene chloride using a lower heat heated hotplate. The resulting mixture was refluxed for one hour, then cooled to 10 to 15 ℃ and stirred for another hour. The mixture was filtered to separate the solid material. The solid was washed several times with dichloromethane and then subjected to a drying step under high vacuum to form pure clomazone crystals (815 kg, purity: 96%). These crystals were identified as type I knock-down by the infrared and X-ray diffraction spectra described in example 2.

Example 5: preparation of form I clomazone

2 grams of clomazone prepared as described in example 1 and 10 grams of Dimethylformamide (DMF) were heated until the clomazone was completely dissolved. The resulting mixture was refluxed for one hour, then cooled to 10 to 15 ℃ and stirred for another hour. The mixture was filtered and the solid was isolated. The solid was washed several times with DMF and then subjected to a drying step under high vacuum to form pure clomazone crystals (815 kg, purity: 96%). These crystals were identified as type I knock-down by the infrared and X-ray diffraction spectra described in example 2.

Example 6: preparation of form I clomazone

2 grams of clomazone prepared as described in example 1 and 10 grams of toluene were heated until the clomazone was completely dissolved. The resulting mixture was refluxed for one hour, then cooled to 10 to 15 ℃ and stirred for another hour. The mixture was filtered and the solid was isolated. The solid was washed several times with toluene and then subjected to a drying step under high vacuum to form pure clomazone crystals (815 kg, purity: 96%). These crystals were identified as type I knock-down by the infrared and X-ray diffraction spectra described in example 2.

Example 7: preparation of form I clomazone

A mixture of 2 grams of clomazone prepared as described in example 1 and 10 grams of DMF and toluene (same parts) was heated until the solid clomazone was completely dissolved. The resulting mixture was refluxed for one hour, then cooled to 10 to 15 ℃ and stirred for another hour. The mixture was filtered and the solid was isolated. The solid was washed several times with a mixture of DMF and toluene (same amount), and then subjected to a drying step under high vacuum to form pure clomazone crystals (815 kg, purity: 96%). These crystals were identified as type I knock-down by the infrared and X-ray diffraction spectra described in example 2.

While the invention has been illustrated and described as including several embodiments, it is not intended to be exhaustive or to limit the invention to all embodiments. Numerous modifications, changes, variations, substitutions and equivalents will occur to those skilled in the art, which fall within the spirit and scope of the present invention as described in the claims.