TWI687417B - Thiamethoxam and uses thereof - Google Patents

Abstract

A crystalline form of 3-(2-chloro-1,3-thiazol-5-ylmethyl)-5-methyl-1,3,5-oxadiazinan-4-yledene (nitro)amine (thiamethoxam) is provided. The crystalline form exhibits an X-ray powder diffraction pattern having characteristic peaks (expressed in degrees 2θ +/- 0.2° θ) at one or more of the following positions: 6.09, 15.37, 17.83, 18.43, 20.86, 22.01, 26.95 and 27.84, and an Infrared (IR) spectrum having characteristic peaks at about 2933.62, 2161.78 and 1593.88 cm^-1. A method of preparing the crystalline form comprises crystallizing 3-(2-chloro-1,3-thiazol-5-ylmethyl)-5-methyl-1,3,5-oxadiazinan -4-yledene (nitro)amine (thiamethoxam) from a solvent system comprising a solvent selected from an alcohol, a glycol, an ether, a ketone, an ester, an amide, a nitrile, an aliphatic or aromatic hydrocarbon, or mixtures thereofl and isolating the resulting crystals.

Description

Thiamethoxam and its uses

The present invention relates to 3-(2-chloro-1,3-thiazol-5-ylmethyl)-5-methyl-1,3,5-oxadiazine-4-ylidene (nitro)amine (thio The form of pyramethoxam, especially the new polymorphic thiamethoxam, and the method of preparation thereof, contains the composition of the new form and its use as an insecticide.

The common name of the known 3-(2-chloro-1,3-thiazol-5-ylmethyl)-5-methyl-1,3,5-oxadiazine-4-ylidene (nitro)amine It is thiamethoxam, which is an agrochemical product with insecticidal activity and widely used in the market. Thiamethoxam and its preparation method were first disclosed in European Patent EP 0 580 553.

Thiamethoxam was first marketed in 1991. It is an osmotic insecticide that can be quickly absorbed by plants and transmitted to various parts of the plant, which can inhibit pests from feeding. Thiamethoxam has gastric toxicity to insects and acts through direct contact. The compound can interfere with the transmission of information between nerve cells, thereby paralyzing pests. Thiamethoxam is effective against aphids, thrips, beetles, centipedes, millipedes, leaf bees, leaf insects, borers and termites. It is said that thiamethoxam can also initiate various physiological reactions, which stimulates the expression of special functional proteins under various emergency defense mechanisms of plants, enabling plants to grow in severe environments.

Thiamethoxam is moderately toxic and does not pose an unacceptable risk during normal use. The substance is toxic to bees and harmful to aquatic and soil organisms, although the magnitude of toxicity to bees is not yet known. The metabolite of thiamethoxam in the soil is clothianidin.

Several methods of preparing thiamethoxam have been reported. Part of the method is based on the reaction between 2-(phenylthio)-5-chloromethyl-thiazole and 3-methyl-4-nitroimino perhydro-1,3,5-oxadiazine, and then The resulting compound is chlorinated. The general reaction sequence of this reaction is as follows:

EP 1 187 833 discloses a simple method for preparing thiamethoxam, that is, 3-methyl-N-nitro-1,3,5,oxadiazine-4-imine and 2-chloro-5-chloromethyl Thiazole reacts in a carbonate solvent, but its yield and purity are not ideal. It is disclosed in the article "Synthesis and Properties of Thiamethoxam and Related Compounds" (quoted from Z. Naturforsch. 61b , (2006), pages 353 to 359.) by P. Maienfisch A similar reaction method. The reaction sequence of this method is as follows:

WO 01/00623 discloses a method for manufacturing various nitroguanidine- and nitroenamine derivatives of the following formula (I). The method includes reacting the compound of formula (II) with the compound of formula (III) in the presence of a base and a phase transfer catalyst.

Crystal particles coated with microcells, including pesticide particles, are disclosed in WO 2013/004705.

The method for preparing thiamethoxam is disclosed in CN 102372702. The method includes dissolving 3-methyl-4-nitroiminotetrahydro-1,3,5-oxadiazine and 2-chloro-5-chloromethylthiazole in a polar aprotic organic solvent and adding potassium iodide as The catalyst and potassium carbonate act as an acid binder and are stirred at room temperature or under heating. The organic solvent used is toluene.

In this field, a simple and effective method for preparing and purifying thiamethoxam is needed, and it can be used in large-scale industrial production to produce safe and high-purity products.

One or more new crystalline form of thiamethoxam has been discovered, and these new crystalline compounds can be prepared and isolated.

The first aspect of the present invention provides a crystalline polymorph 3-(2-chloro-1,3-thiazol-5-ylmethyl)-5-methyl-1,3,5-oxadiazine-4-ylidene (Nitro)amine (thiamethoxam).

In a preferred embodiment, thiamethoxam is provided in polymorphic form and is referred to herein as "polymorph A".

In another aspect, the present invention provides an insecticide composition containing crystalline polymorph thiamethoxam.

In this regard, the insecticide composition of the present invention can control insects in agricultural and horticultural crops. In one embodiment, the composition comprises thiamethoxam in crystalline polymorph form A.

The present invention also relates to a method of deinsecting at a point of application. The method includes applying a polymorphic form of thiamethoxam, especially crystalline polymorph A, at a point of application with an insecticidal efficacy dose.

In the method of the present invention, the point of application may be a protected plant, a protected area around the plant, or a protected plant seed.

The invention also relates to a method for protecting crops, such as agricultural and horticultural crops, including its industrial products, such as seeds and fruits. The method is to apply an effective dose of thiamethoxam, especially polymorph A, to crops.

The solid exists in amorphous or crystalline form. The molecules of a solid in crystalline form are arranged in a three-dimensional lattice. If a compound is formed by recrystallization from a solution or slurry, the crystals may have different spatial lattice arrangements. This feature is called "polymorphism", and each different crystal form is called a "polymorphism". Crystal form". The same substance of different polymorphs may have one or more different physical characteristics, such as solubility, decomposition, true density, crystal shape, compression properties, flow characteristics and/or stability of the solid state.

For chemicals with two (or more) polymorphic forms, usually at a certain temperature and for a sufficient time, the unstable crystalline form will be transformed into a more thermodynamically stable crystalline form. If the transformation process is not rapid, the thermodynamically unstable crystal form is called the "meta-stable" crystal form. Stable crystal forms usually have the highest melting point, the lowest solubility and the strongest chemical stability. However, even under ordinary storage conditions, the metastable crystal form has sufficient chemical and physical stability and can be used as a commercial crystal form. In addition, although the stability of the metastable crystal form is weak, there are advantages that the stable crystal form does not have, such as better plasticity and improved water dispersibility.

As far as the applicant is aware, 3-(2-chloro-1,3-thiazol-5-ylmethyl)-5-methyl-1,3,5-oxadiazine-4-ylidene (nitro)amine The crystal form of (thiamethoxam) is unknown.

After extensive research, the inventor of the present invention discovered a new thiamethoxam crystal form, which is referred to herein as "crystal form A". Under the unique X-ray diffraction pattern and infrared (IR) spectrum, the new crystal form shows unique spectral characteristics.

For example, as shown in Figure 1, the X-ray powder diffraction pattern of Form A has characteristic peaks (the error degree of 2θ is +/- 0.2° θ) at one or more of the following positions: 6.09, 15.37, 17.83, 18.43, 20.86 , 22.01, 26.95 and 27.84.

The X-ray powder diffraction pattern shown in Figure 1 was obtained with the Philips powder diffractometer PW 1050/70. Its operating tube pressure and tube flow were 40 kV and 30 mA, respectively, using uKα rays (wavelength 1.54178Å) and diffracted beam graphite Monochromator. A typical 0-20 scan range is 3-35° 2 Theta, with a step size of 0.05° and a calculation period of 0.5 seconds per step. The sample was ground with an agate mortar and pestle, and the resulting powder was filled into an aluminum sample holder with a rectangular cavity of 20 mm x 15 mm x 0.5 mm.

In addition, as shown in FIG. 2, the infrared (IR) spectrum of Form A exhibits characteristic peaks at about 2933.62, 2161.78, and 1593.88 cm ^-1 .

Infrared spectroscopy is measured in a DuraSamplIR ^™ sample device, a diamond optical window ReactIR ^™ 1000 Fourier transform infrared spectroscopy (FT-IR) analyzer (Attenuated Total Reflection (ATR) method, MCT detector) manufactured by Mettler Toledo Autochem. The diamond detector has a standard zinc selenide focusing lens. The powdery sample was filled in the sample device, and the measurement resolution was 4 cm ^-1 and 256 scan times.

In another aspect, the present invention provides a method for preparing polymorph A of thiamethoxam. Preparation of crystalline form A thiamethoxam, which can be crystallized from a solvent system containing the following ingredients: alcohol, glycol, ether, ketone, ester, amide, nitrile, aliphatic or aromatic hydrocarbon, or mixtures thereof ; Then separate the obtained crystal.

In a presently preferred embodiment, the solvent is alcohol, especially C ₁ to C ₄ alcohol, especially methanol, ethanol, or propanol, especially 1-propanol; diol, especially C ₁ to C ₄ diols, especially ethylene glycol; aromatic hydrocarbons, especially substituted benzene derivatives, especially xylene; or mixtures thereof. With regard to substituted benzene derivatives, it has been found that toluene as used in the prior art is not a satisfactory solvent. In particular, it has been found that crystalline thiamethoxam made using toluene as a solvent has significantly lower stability than crystalline thiamethoxam made using other solvents mentioned above.

Therefore, in another aspect, the present invention provides a method for preparing crystalline thiamethoxam, the method comprising crystallizing thiamethoxam from a solvent system, the solvent system comprising an alcohol, glycol, ether, ketone, ester, amide, Solvents for nitriles, aliphatic or aromatic hydrocarbons, or mixtures thereof; and crystals isolated; but the solvent system does not contain toluene.

In one embodiment, the method includes preparing a thiamethoxam solution from one or more of the aforementioned solvents, preferably heating until completely dissolved, gradually cooling the solution until crystals appear, and then isolating the crystals. Usually only need to cool down to room temperature, but the solution can also be cooled to a lower temperature, such as 0 ℃., 5 ℃., 10 ℃., 15 ℃. or similar temperatures. Gradual cooling is commonly used, such as stopping heating and allowing the solution to cool at room temperature.

As far as known in the art is concerned, when the thiamethoxam solution forms crystals, a seed crystal of Form A may be added to promote crystallization.

The thiamethoxam starting materials used to prepare Form A can be prepared by methods known in the art. A preferred way to form thiamethoxam is 3-methyl-N-nitro-1,3,5, oxadiazine-4-imine and 2-chloro-5-chloromethylthiazole as follows Reaction process:

The above reaction is carried out in the presence of a solvent or diluent, a phase transfer catalyst and a base. The preferred solvent or diluent is a polar aprotic solvent, the phase transfer catalyst is a quaternary ammonium salt and the base is a carbonate. In particular, dimethylformamide (DMF) is a solvent particularly suitable for carrying out the above reaction. A suitable phase transfer catalyst is triethylbenzyl ammonium chloride (TEBA). The base used is preferably potassium carbonate.

The crystalline form of thiamethoxam in the present invention can be formulated and composed of insecticide compositions using techniques known in the art. The summary is as follows: The liquid can be added to an emulsion, paste or wettable powder ( Spray powder, disperse oil) to prepare. In the preparation of emulsions, pastes or dispersing oils, in order to make the active ingredient or the active ingredient dissolved in oil or solvent can be evenly dissolved in water, wetting agent, thickener, dispersant or emulsifier can be added during stirring. However, it is also possible to prepare concentrates composed of active substances, wetting agents, tackifiers, dispersants or emulsifiers and appropriate amounts of solvents or oils, and this concentrate is also suitable for dilution with water.

When preparing ready-made preparations, the active compound concentration can be varied within a relatively wide range. Generally, a suitable concentration weight percentage range is 0.0001 to 10%, preferably 0.01 to 1%.

The following are examples of different formulations of the thiamethoxam product of the present invention.

1. The product applied to the leaf surface after dilution with water can be prepared as follows. The formulation can also be used for seed dressing, and whether it is diluted for seed treatment purposes.

A) Aqueous solution (SL, LS)

By weight, 10 parts of active compound are dissolved in 90 parts of water or a water-soluble solvent. Wetting agents or other additives can be added. After dilution with water, the active compound is dissolved to obtain a formulation containing 10% (w/w) active compound.

B)Water-dispersible emulsion (IDC)

Based on the total amount, 20 parts of active compound are dissolved in 70 parts of cyclohexanone, and then 10 parts of dispersant, such as polyvinylpyrrolidone, are added. Dilute with water to a dispersion to obtain a formulation containing 20% (w/w) active compound.

C) Emulsion (EC)

By weight, 15 parts of the active compound are dissolved in 80 parts of xylene, and then calcium dodecylbenzenesulfonate and castor oil ethoxylate (5 parts by weight) are added. Dilute into an emulsion with water to obtain a formulation containing 15% (w/w) active compound.

D) Emulsion (EW, EO, ES)

By weight, 25 parts of the compound was dissolved in 35 parts of xylene, and then calcium dodecylbenzenesulfonate and castor oil ethoxylate (5 parts by weight) were added. The mixture is added to 30 parts by weight of water using an emulsifier (such as Ultraturrax) to form a homogeneous emulsion. Dilute into an emulsion with water to obtain a formulation containing 25% (w/w) active compound.

E) Suspending agent (SC, OD, FS)

Using a stirring bead mill, 20 parts by weight of active compound plus 10 parts of dispersant, wetting agent and 70 parts of water or an organic solvent are crushed to obtain a suspension containing finely milled active compound. Dilute with water to form a stable active compound suspension to obtain a formulation containing 20% (w/w) active compound.

F) Water-soluble granules and water-soluble granules (WG, SG)

By weight, 50 parts of active compound plus 50 parts of dispersant and wetting agent are finely ground, and then prepared into water-dispersible or water-soluble granules using technical equipment (such as extrusion, spray tower, fluidized bed). Dilute with water to form a stable active compound dispersant or solution to obtain a formulation containing 50% (w/w) active compound.

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

By weight, grind 75 parts of active compound, 25 parts of dispersant, wetting agent and silicone in a stirred ball mill. Dilute with water to form a stable active compound dispersant or solution to obtain a formulation containing 75% (w/w) active compound.

H) Gel (GF) (only used for seed dressing)

Using a stirring bead mill, 20 parts by weight of active compound plus 10 parts of dispersant, 1 part of gelling agent/wetting agent and 70 parts of water or an organic solvent are crushed to form a suspension of finely ground active compound Agent. Dilute with water to form a stable active compound suspension to obtain a formulation containing 20% (w/w) active compound.

2. The preparation method of the product that can be applied to the leaf surface undiluted is as follows. When used for seed dressing, the product can be diluted before processing the seeds.

I) Powder (DP, DS)

By weight, 5 parts of active compound are ground finely, and then fully mixed with 95 parts of fine kaolin to obtain a powder product containing 5% (w/w) active compound.

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

On a weight basis, 0.5 parts of active compound was ground and then 95.5 parts of carrier was added to obtain a formulation containing 0.5% (w/w) active compound. Existing methods for preparing granules include extrusion, spray drying, or the use of a fluidized bed to obtain undiluted granules that can be applied to the foliage.

K) Microcapsule (ME)

By weight, 0.5 parts of active compound is ground, and then 95.5 parts of the mixture of polyurea, crosslinking agent and carrier is added to obtain a formulation containing 0.5% (w/w) of active compound, thereby preparing a solution containing 5% (w /w) A microcapsule product of the active compound, the active ingredient in the microcapsule is encapsulated in a microcapsule with a polymer shell.

L) Microcapsules (MEG)

Based on weight, 0.5 parts of active compound is ground, then 95.5 parts by weight of polyurea, crosslinking agent, solid carrier and binder are added to form a mixture, and the resulting mixture is formed into granules; a composition containing a binder is used Wrap the granules; then dry the coated granules. Through this procedure, microencapsulated active ingredient particles containing 5% (w/w) active compound can be prepared.

Specific examples of the present invention are explained by the following examples.

Examples Example 1: Synthesis of thiamethoxam

1.1 Preparation of 3,6-dihydro-3-methyl-N-nitro-2H-1,3,5,oxadiazine-4-amine for the preparation of 3,6-dihydro-3-methyl- Reaction scheme of N-nitro-2H-1,3,5,oxadiazine-4-amine:

100 kg of N-methyl-nitroguanidine and 64 kg of polyoxymethylene were added to the 1000 L reactor. 350 kg of acetic acid was added, the resulting mixture was heated to 70°C, and the temperature was maintained for 6 hours, and then the solvent (acetic acid) was removed by vacuum distillation. 175 kg of 10% NaOH aqueous solution was added, stirring was continued, and then the resulting mixture was cooled and stirred for 30 minutes, and then the resulting mixture was placed in a centrifuge to separate. The cake obtained was dried with a double cone dryer to obtain 98 kg of 3-methyl-N-nitro-1,3,5,oxadiazine-4-imine as a white powder (purity 97%, yield 71.5 %).

1.2 Preparation of 2-chloro-allyl thioisonitrile

Reaction flow chart for preparing 2-chloro-allyl thioisonitrile:

In a 500L reactor, 60.5 kg of 2,3-dichloropropene was mixed with 135 kg of toluene, 0.5 kg of triethylbenzyl ammonium chloride (TEBA as a catalyst), and 44.1 kg of sodium thiocyanate. The resulting mixture was heated to reflux for 1.5 hours (about 100-105°C), and then cooled to room temperature. 50 kg of water was added and stirring continued for 15 minutes, then the mixture was allowed to stand for separation. The formaldehyde in the organic phase was removed under vacuum, and the residue was distilled under high vacuum using a Roots Vacuum Pump. 65 kg of 2-chloro-allyl thioisonitrile distillate was recovered to obtain a yellow oil (yield 80%, purity 90%).

1.3 Preparation of 2-chloro-5-(chloromethyl)thiazole

Reaction flow chart for preparing 2-chloro-5-(chloromethyl)thiazole:

In a 500L enamel reactor, 65 kg of 2-chloro-allyl thioisonitrile was mixed with 140 kg of carbon tetrachloride. 35 kg of chlorine was bubbled into the mixture for one hour, and the resulting mixture (77° C.) was heated to reflux for 3 hours, and then cooled to room temperature. Carbon tetrachloride is removed by distillation. 59 kg of dichloromethane was added, stirring was continued until the residue was dissolved, and then the solution was washed with 86 kg of saturated NaHCO ₃ solution and 40 kg of water. The obtained mixture was dried with anhydrous MgSO ₄ , and the methylene chloride was removed by vacuum distillation. Finally, the reaction was separated by high vacuum distillation using a Roots vacuum pump to obtain 61 kg of 2-chloro-5-(chloromethyl)thiazole as a yellow liquid (yield 84%, purity 96%).

1.4 Preparation of Thiamethoxam

Reaction flow chart for the preparation of thiamethoxam:

47.5 kg of 3-methyl-N-nitro-1,3,5-oxadiane-4-imine and 50 kg of 2-chloro-5-(chloromethyl)thiazole were fed to contain 350 kg of dimethyl In a 1000L enamel reactor based on methylformamide (DMF). The resulting mixture was heated and the temperature was maintained at 65°C. Then, 82 kg of potassium carbonate and 1 kg of triethylbenzyl ammonium chloride (TEBA as a catalyst) were added to the reactor for 20 to 40 minutes. The resulting mixture was reacted for 4 to 5 hours, and then the mixture was cooled to room temperature. Add 280 thousand in the reactor Grams of water, the mixture was stirred for 15 minutes, and the pH was adjusted to 6 and 7 with 32% hydrochloric acid. The mixture was vigorously stirred and heated to 65°C. The resulting mixture was allowed to stand for 30 minutes, and the aqueous phase was separated and extracted with dichloromethane (DCM) (100 kg×3) for three times. The organic phases were mixed and DCM was removed by vacuum distillation. The mixture was dried with a double cone dryer at a temperature of 40°C to obtain crude thiamethoxam.

Example 2: Preparation of thiamethoxam form A

In 10 g of methanol, 2 g of thiamethoxam prepared in Example 1 was heated until completely dissolved. The resulting solution was heated to reflux for 30 to 60 minutes, and then cooled to room temperature. The resulting mixture was filtered to separate solids. The solid was washed with methanol several times, and dried under high vacuum to obtain pure thiamethoxam crystals (purity: 98%).

Infrared (IR) spectrometer and X-ray diffractometer confirmed that the crystal was thiamethoxam form A.

Form A Thiamethoxam

The X-ray powder diffraction pattern is attached to Figure 1, and the reflection values are listed in Table 1 below.

Figure 2 shows the infrared spectrum of crystalline form A thiamethoxam. The infrared spectrum shows characteristic peaks at positions 2933.62, 2161.78, and 1593.88 cm ^-1 .

Example 3: Preparation of thiamethoxam form A

2 grams of thiamethoxam prepared according to Example 1 was dissolved in 10 grams of xylene while heating with a hot plate at low temperature. The resulting mixture was heated to reflux for 30 to 60 minutes, and then cooled to room temperature. The resulting mixture was filtered to isolate the solid. After filtration, the solid was washed with xylene several times, and then dried under high vacuum to obtain pure thiamethoxam original crystals (purity: 97%).

As described in Example 2, the crystal was determined to be thiamethoxam form A using an infrared spectrometer and an X-ray diffractometer.

Example 4: Preparation of thiamethoxam form A

2 grams of thiamethoxam prepared according to Example 1 and 10 grams of ethylene glycol were heated until thiamethoxam was completely dissolved. The resulting mixture was heated to reflux for 30 to 60 minutes, and then cooled to room temperature. The resulting mixture was filtered to isolate the solid. After filtration, the solid was washed several times with ethylene glycol and dried under high vacuum to obtain pure thiamethoxam original crystals (purity: 96%).

As described in Example 2, the crystal was determined to be thiamethoxam form A using an infrared spectrometer and an X-ray diffractometer.

Example 5: Preparation of thiamethoxam form A

Heat 2 grams of thiamethoxam prepared according to Example 1 with 10 grams of ethanol until thiamethoxam is completely dissolved. The resulting mixture was heated to reflux for 30 to 60 minutes, and then cooled to room temperature. The resulting mixture was filtered to separate the solid. After filtration, the solid was washed several times with ethanol and then dried under high vacuum to obtain crystals of pure thiamethoxam original drug (purity: 96%).

As described in Example 2, the crystal was determined to be thiamethoxam form A using an infrared spectrometer and an X-ray diffractometer.

Example 6: Preparation of thiamethoxam A

2 grams of thiamethoxam prepared according to Example 1 and 10 grams of 1-propanol were heated until the solid thiamethoxam was completely dissolved. The resulting mixture was heated to reflux for 30 to 60 minutes, and then cooled to room temperature. The resulting mixture was filtered to isolate the solid. After filtration, the solid was washed with 1-propanol several times and then dried under high vacuum to obtain crystals of pure thiamethoxam original drug (purity: 97%).

As described in Example 2, the crystal was determined to be thiamethoxam form A using an infrared spectrometer and an X-ray diffractometer.

Comparative Example A: Preparation of Thiamethoxam Form A

2 grams of thiamethoxam prepared according to Example 1 and 10 grams of toluene were heated until completely dissolved. The resulting mixture was heated to reflux for 30 to 60 minutes, cooled to room temperature, and the resulting mixture was filtered to isolate the solid. The solid was washed with toluene several times, and then dried under high vacuum to obtain pure thiamethoxam crystals (purity: 97%).

As described in Example 2, the crystal was determined to be thiamethoxam form A using an infrared spectrometer and an X-ray diffractometer.

Photolysis stability test

The samples of thiamethoxam prepared in Examples 1 to 6 and Comparative Example A were tested using the following procedure to determine their photolytic stability: 20 liters of thiamethoxam aqueous solution (50 mg/liter) was added to the quartz tube. The tube was continuously irradiated with UV light from a UV lamp. 100 microliters of solution were taken from the tube every 10 minutes. The concentration of thiamethoxam in each aliquot was determined by gas chromatography (GC) and mass spectrometry (MS).

The results are summarized in Table 2 below.

It can be seen from the data in the above table that the crystalline thiamethoxam obtained in each of Examples 2 to 6 exhibited extremely high photolytic stability compared to the crude thiamethoxam of Example 1. In addition, the results show that the preparation of crystalline thiamethoxam by crystallization from a toluene solution produces a crystalline product with poor photolysis stability.

Although the invention illustrates and describes several embodiments, it is clear that the invention is not limited to the embodiments described herein. It is obvious to those skilled in the art that various modifications, changes, changes, substitutions, and equivalents can be made without departing from the scope of the invention contained in the scope of the patent application. The scope of patent application is as follows.

Claims (5)

Preparation of 3-(2-chloro-1,3-thiazol-5-ylmethyl)-5-methyl-1,3,5-oxadiazine-4-ylidene (nitro)amine (thiamethoxam ) Crystal method, the method includes forming 3-(2-chloro-1,3-thiazol-5-ylmethyl)-5-methyl-1,3,5-oxadiazine from a solvent system Crystallization of -4-ylidene (nitro)amine (thiamethoxam), the solvent system contains a solvent selected from alcohols, diols or aromatic hydrocarbons, or mixtures thereof; It does not contain toluene; where the alcohol is methanol, ethanol, or propanol; the glycol is ethylene glycol; and the aromatic hydrocarbon is xylene. The method of claim 1, wherein the solvent system is alcohol, diol, aromatic hydrocarbon, or a mixture thereof; wherein the alcohol is methanol, ethanol, or propanol; the glycol is ethylene glycol; and the aromatic hydrocarbon is xylene. The method of claim 1 or 2, wherein the alcohol is 1-propanol. The method of claim 1 or 2, wherein the solvent system is cooled to a temperature of 0 to 15°C. The method according to claim 1 or 2, wherein 3-(2-chloro-1,3-thiazol-5-ylmethyl)-5-methyl-1,3 of claim 1 or 2 is added to the solvent system The crystal form of 5-oxadiazine-4-ylidene (nitro)amine (thiamethoxam) is used as a seed crystal.

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