GB2514927A

GB2514927A - Thiamethoxam and uses thereof

Info

Publication number: GB2514927A
Application number: GB1409423.9A
Authority: GB
Inventors: James Anthony Bristow
Original assignee: Rotam Agrochem International Co Ltd
Current assignee: Rotam Agrochem International Co Ltd
Priority date: 2014-05-28
Filing date: 2014-05-28
Publication date: 2014-12-10
Anticipated expiration: 2034-05-28
Also published as: AR100637A1; CN105175407B; TWI687417B; GB201409423D0; CN105175407A; MY180015A; TW201546068A; BR102015012164A2; GB2514927B

Abstract

A crystalline form of 3-(2-chloro-1,3-thiazol-5-ylmethyl)-5-methyl 1,3,5-oxadiazinan-yledene (nitro)amine (thiamethoxam) is provided. The crystalline form exhibits an X-ray powder diffraction pattern having characteristic peaks (expressed in degrees 2Æ +/- 0.2Â° Æ) 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 thereof; and isolating the resulting crystals. The exemplified solvents are methanol, ethanol, 1-propanol, ethylene glycol, toluene and xylene.

Description

THIAMETHOXAM AND USES THEREOF

The present invenfion relates to forms of 3-(2-chloro-1,3-thiazol-5-ylmethyl)-5-methyl-i,3,5-oxadiazinan-4-yledene (nitro)amine (thiamethoxam), in particular to novel crystafline polyrnorphs of thiamethoxam, to processes for their preparation, compositions comprising the new forms, and their use as insecticidal agents.

3-(2-chioro-1,3-thiazol-5-ylmethyi)-5-methyl-i,3,5-oxadiazinan-4-yedene (nitro)amine, known by the common name thiametnoxam, is a wvdely used commercial agrochemcal product exhibiUng insecticidal activity. Thiamethoxam was first disclosed in EP 0 580 553, along with methods for its preparation.

Thiamethoxani was first marketed in 1991 and is a systemic insecticide that is absorbed quickly by plants ar.d transported to all parts of the plant, where it acts as a deterrent to insect feeding. Thiamethoxam is active in the stomach of the insects and also acts through direct contact. The compound interferes with information transfer between nerve cells, in turn paralyzing the insects. Thiamethoxam is effective against aphids, thrips, beetles, centipedes, millipedes, sawf lies, leaf miners, stem borers and termites. It. has also been asserted that thiamethoxam triggers var!ous physiological reactions, which induce the expression of spec!tic funcUonal proteins involved in various stress defense mechanisms of the plant allowing it to better cape under tough growing conditions.

Thiamethoxarn is a moderately toxic substance. In normal use, there are no unacceptable risks involved. The substance is toxic to bees and harmful to aquatic and wi; organisms, although [he level or toxicity to bees is not yet clear. A metabolite of thiamethoxam in soil is clothianidin.

There are several reported ways of making thiamethoxam, Severn! methods are based on the reaction of 2-(pheny!thio)-5-chlcrcrnethyk.hiozole and 3-methvl-4-nitroiminoperhydro*-i,3,5-oxadiazine, foflowed by chlorinaflon of the resulting compound. The general procedure of this reaction sequence is as foHows: (j-cu-s---ç5-ciça + 1-___c-Orç 2-(phenylthio)-5-chloro 3-methyl-4-nitroirnino methyl-thiozole perhydro-1,3,5-oxadiazine Q_cFs)_cHrçi_cr{3 Cl2 N-NO, N-NO2 thiamethoxam EP 1 187 833 discioses a simple method for preparing thiamethoxarn by reacting 3-methyl-N-nitro-1 3,5, oxadiazinan-4lmine and 2-ch!oro-5-chloromethyl thiazole in a so!vent of ester of carbonic acid. However, the yield and purity is not satisfactory. A simi!ar reaction scheme is disclosed by P. Maienfisch Synthesis and Properties of Thiamelhoxam arid Related Compounds, 1 Naturforsch. 61b, (2006), pages 353 to 359. The reaction sequence for this method is as follows: a. i r_i NNO2 + ester of carbonic acid thiamethoxam There is a need in the art for efficient methods for tile preparation and purification of thiamethoxam, which are simple and can be used on a large scale For industrial manufacture, and which produce highly pure product that car. be safely utihzed.

It has now been found that thiamethoxam can exist in one or more novel crystafline forms and the compound can be prepared and isolated in these novel forms.

in a first aspect, the present invention provides crystalhne polymorphic forms of 3-(2-chbro-1,3thiazol-5-ylmethyl)-5-methyi-1,3.5-oxadiazinan 4-yledene (nitro)amine (thiamethoxam).

In a preferred embodiment, thiamethoxam is provided in a polymorphic form referred to herein as "polymorph Form A" in another aspect, the present invention provides insecticide compositions comprising thiamethoxam present in a crystalline polymorphic form.

The insecticide compositions of this aspect of the invention are useful for controlling insects in agricultural and horticultural crops. In one embodiment. the compositions comprise thiamethoxam in crystaUine polymorph Form A. The present invention also relates to methods for combating insects at a locus, the method comprising applying to the locus an isecticidally effective amount of thianiethoxam in a crystafline poiymorphic form, in particuar crystalline polymorph Form A. in the method of the present invention, the locus may be a plant to be protected, a region surrounding a plant to be protected, or a seed of the plant.

The present invention also relates to a method for protecting crops, such as agricultural arid horucultural crops, including industrial products thereof, such as seeds and fruits, by applying to the crops an effective amount of thiamethoxam in a crystaWne polymorphic form, in particular crystafline polymorph Form A. Solids exist in either amorphous or crystalUne forms. In the case of crystalline forms, molecules are positioned in 3dirnensionaI lattice sites. When a compound recrystaflizes from a solution or slurry, ii may crystaUize with different spatial lattice arrangements, a property referred to as "polymorphism," with [he different crystal forms individuaUy being referred to as a "polymorph". Different polymorphic forms of a given substance may differ from each other with respect to one or more physical properties, such as solubflity and dissociation, true density, crystal shape, compaction behavior, flow properties, and/or solid state stabifity. In the case of a chemical substance that exists in two (or more) polymorphic forms, the unstable forms generally convert to the more thermodynamically stable forms at a given temperature after a sufficient period o time. When this transformation is not rapid, the thermodynamically unstable form is referred to as the metastabie" form.

In general, the stable form exhibits the highest melting point, Ihe lowest solubility, and the maximum chemical stab!lity. However, the metastable form may exhibit sufficient chemical and physical stability under normal storage conditions to permit its use in a commercial form. Furthermore, the metastable form, although less stable may exhibit properties desirable over those of the stable form, such as better formative ability, improved dispersability in water, and the like.

S

To the Apphcants best knowedge, in the case of 3-(2-*chbro-13-thiazoF-5-ylmethyl) -5-methyki,3,5-oxadiazinan-4-yiedene(rutro)amine (thiamethoxam), no crystafline forms are known.

The inventors of the present invention, after extensive research, have discovered a new crystafline form of thiamethoxam. designated herein Form A'. The new form exhibits specific spectral characteristics as depicted by the distinct X-ray diffraction patterns and infrared (R) spectra.

For examp'e, as shown in Figure 1, Form A exhibits an X-ray powder diffraction pattern having characteristic peaks (expressed in degrees 28 ±1-0.2° 8) at one or more of the foUowing positions: 609, 1527, 1783, 18.43, 20.86, 22.01, 2695 and 27.84.

The X-Ray powder diffraction pattern shown in Figure 1 was coDected on a Phihps powder diffractometer PW 1050/70 operated at 40 kV and 30 mA using uKa radiation (wav&ength equal to 1.54178 A) and a diffracted beam graphite monochromator. The typica 0 -20 scan range was 3-3502 Theta with a step size oF 0.05° and a count time of 0.5 seconds per step. The samples were ground using an agate mortar and peslie. The powder so obtained was then pressed into an aluminum sampe hoVder with rectanguar cavdy with dimensions of 20 mm x 15 mm and a depth of 0.5 mm.

Furthermore, as shown in Figure 2, Form A aso exhibits an nfrared (R) spectrum having characteristic peaks at about 2933.62, 2161.78 and 1593.88 cm1, The A spectrum was measured using a Fourier transform infrared (FT-IA) spectrophotorneter ReactlA'1 1000 of MetUerToedo Autochem (ATR method, MOT detector), diamond window, in a DuraSarnpflRTM sampUng device. The diamond sensor had a standard focusing opflc of ZnSe. The powdered samples were compressed in the sampling device and were measured with resolution of 4 cm arid 256 scans.

in another aspect, the present invention provides processes for preparing the novel thiamethoxam polymorph Form A. Form A thiamethoxam can he prepared by crystaflizing thiamethoxam from a solvent system comprising a solvent selected from an alcohol. a glycol, an ether, a ketone. an ester, an arnide, a nitrUe, an aliphatic or aromatic hydrocarbon, or mixtures thereof; and isolating the resulting crystals.

In a currently preferred embodiment, the solvent s an alcohol, especially a C to C4 alcohol, in particular methanol, ethanol, or propanol, especially 1-propanol; a glycol, especially a C1 to C4 glycol, in particular ethylene glycol; an aromatic hydrocarbon, especially a substituted benzene derivative, in particular xylene, or toluene; or mixtures thereof.

In one embodiment, the process includes preparing a solution of thiamethoxam in one or more of the aforementioned solvents, preferably by applying heat until dissolution is complete, gradually cooling the solution until crystals appear, and isolating the crystals. Generally, cooling to room temperature is sufficient, however, the solution can be cooled to lower temperatures, for example 0°C., 5°C., 10° C., 15°C. and the like. Gradual cooling is typically achieved, for example by removing the heat and ailowing the solution to cool under ambient conditions.

The formation of crystals from the solution of thiamethoxam may be seeded with Form A seed crystals, in order to induce crystallization, as known in the art.

The thiamethoxam starting matenia used tor preparing Form A can be prepared by methods known in the art. One preferred route to forming thiamethoxam is the reaction of 3-methyl-N-nitro -1,3,5, oxadiazinan-4-imine and 2-chloro-5-chloromethyl thiazole, according to the following general reaction scheme: + Hck Cl)NY NO2 2-chloro-5-chloro 3-methyl-N-nitro-1, 3,5,oxadiazinan thiamethoxam methyl thiazole -4-imine The above reaction is conducted in the presence of a solvent or diluent, a phase transfer catalyst and a base, preferably the solvent or diluent being a polar aprotic solvent, the phase transfer catalyst being a quaternary ammonium salt and the base being a carbonate. DMF is a particularly suitable solvent for conducting the above reaction. A suitable phase transfer catalyst is triethyl benzyl ammonium chloride (TEBA). The base used is preferably potassium carbonate.

Thiamethoxam in Form A as provided herein may be formulated and incorporated into insecticidal compositions using techniques known in the art. These are summarized as foliows: Aqueous use forms can be prepared from emLflsion concentrates, pastes or wettable powders (sprayabie powders, oil dispersions) by adding water. To prepare emulsions, pastes or oil dispersons, the active ingredients, as such or dissoived in an oil or solvent, can be homogenized in water by means of stirring with a wetter, tackitier, dispersant or emulsifier, However, it is also possible to prepare concentrates composed of an active substance, wetter, tackifier, dispersant or emulsifier and, if appropriate, solvent or o, arid such concentrates are suitable for dUution with water.

The active compound concentrations in the ready-to-use preparations can be varied within relatively wide ranges. ri general, suitable concentrations are from 0.0001 to 10%, preferably from 0.01 to 1% per weight.

The foflowing are examples of formulations of the thiamethoxamn products of the present invention: 1. Products for dilution with water for foliar applications may be prepared as foDows.

The formulations may also be applied to seeds, either with or without dflution, for seed treatment purposes.

A) Water-Soluble Concentrates (SL, LS) 10 parts by weight of the active compound(s) are dissolved in 90 parts by weight of water or a water-soluble solvent. Wetters or other auxiliaries may be added. The active compound(s) dissolves upon dilution wit.h water, whereby a formulation with i0°/ (w/w) of active compound(s) is obtained.

B) Disoersibie Concentrates (DC) parts by weight of the active compound(s) are dissolved in 70 parts by weight of cyclohexanone with the addition of 10 parEs by weight or a dispersant, for example polyviny!pyrrolidone. Dilution with water gives a dispersion, whereby a formulation with 20% (w/w) of acfive compound(s) is obtained.

C) Ernusifiab!e Concentrates (EC) pads by weight of the active compound(s) are disso'ved in 80 parts by weight of xyene with the addition of cacium dodecybenzenesuftonate and castor oU ethoxyiate (in each case 5 parts by weight). Dilution with water gives an emu!sion, whereby a formulation with 15% (w/w) of active compound(s) is obtained.

D) Emusions (EW, EO. ES 25 pads by weight of the active compound(s) are disso'ved in 35 parts by weight of xyene with the addition of cacum dodecytenzenesuifonate and castor oi ethoxyate (in each case 5 parts by weight). This mixture is introduced into 30 parts by weight ci water by means of an emusifier machine (for exampe an Ultraturrax) and formed into a homogeneous emulsion. Dilution with water gives an emu'sion.

whereby a formulation with 25% (w/w) of active compound(s) is obtained.

E) Suwensions (SC, OD. FS in an ag!tated baD milL 20 pads by weight of the active compound(s) are comm!nuted with the addition of 10 parts by weight of dispersants, wetters and 70 pads by weight of water or of an organic solvent to give a fine active compound(s) suspension.

Dilution with water gives a stab'e suspension of the active compound(s), whereby a formuation with 20% (w/w) of active compound(s) is obtained.

F) Water-Dispersible Granules and Water-Soluble Granules (WG. SO) parts by weight of the active compound(s) are ground finely with the addition of 50 parts by weight of dispersants and wetters and formed as water-dispersible or water-soluble granules by means of technical appliances (for example extrusion, spray tower, fluidized bed). Dilution with water gives a stable dispersion or solution of the active compound(s), whereby a formulation with 50% (w/w) of active compound(s) is obtained.

G) Water-Dispersible Powders and Water-Soluble Powders (WP, SR. SS. WS) 75 parts by weight of the active compound(s) are ground in a rotor-stator mill with the addition of 25 parts by weight of dispersants, wetters and silica gel. Dilution with water gives a stable dispersion or solution of the active compound(s), whereby a formulation with 75% (w/w) of active compound(s) is obtained.

H) Gel-Formulation (OF) (for Seed Treatment Purposes Only) In an agitated ball mill, 20 parts by weight of the active compound(s) are comminuted with the addition of 10 parts by weight of dispersants, 1 part by weight of a gelling agent/wetters and 70 parts by weight of water or of an organic solvent to give a fine active compound(s) suspension. Dilution with water gives a stable suspension of the active compound(s), whereby a formulation with 20% (wlw) of active compound(s) is obtained.

2. Products to be apped undiluted for foflar appHcafions may be prepared as follows. For seed treatment purposes, such products may be apphed to the seed diluted.

I) Dustable Powders (DP. DSI parts by weight of the active compound(s) are ground Iineiy and mixed intimately with 95 parts by weight of fine'y divided kaohn. This lormulation gives a dus[abe product having 5% (w/w) of active compound(s).

J) Granules (OR, FO, GO. MG) 0.5 parts by weight of the active compound(s) is ground finely and associated with 95.5 parts by weight of carriers, whereby a formulation with 05% (wlw) of active compound(s) is obtained. Current methods for preparing granules include extrusion, spray-drying or use of a fluidized bed. This gives granues to be applied undiluted for foliar use.

K) Microcasuation. ME 0.5 parts by weight of the active compound(s) is ground finely and associated with 95.5 parts by weight of a mixture of polyurea, crosslinker, and carriers, whereby a formulation with 0.5% (w/w) of active compound(s) is obtained. This gives a microencapsulation product having 5% (w/w) of active compound(s), in which the active ingredient 5 encapsulated within microcapsules having a polymer shell.

es MEG 03 part by weight of the active compound(s) is ground finely and associated with 95.5 parts by weight of polyurea, crossUnker, a sofid carrier and a binder to form a mixture, forming granules from the resulting mixture; applying a composition comprising a binder to coat the granules; and drying the thus coated granules. This procedure gives a microencapsulated active ingredient within granules having 5% (w/w) of active compound(s).

Embodiments of the present invenUon will now be illustrated by the following

specific examples.

EXAMPLES

Example 1: Synthesis of Thiamethoxam 1.1 Preparation of 3,6-dihydro-3-methyl-N-nitro-2H-1,3.5,oxadiazin-4-amine 3,6-dihydro-3-methyl-N-nitro-2H-1,3,5,oxadiazin-4-amine was prepared using following reaction scheme: TIN7 _____N acetic acid Faraformaldchydc uN N TI7N 70°C I NNfl N-methyl-nitroguanidine 3-methyl-N-nitro-1 3,5, oxadi az in an-4-i mine 100 kg of N-methyl-nitroguanidine and 64 kg of Paraformaldehyde were charged to a 1000 L reactor. 350 kg of acetic acid was added, after which the resulting mixture was heated to 70t and held at this temperature for 6 hours. Thereafter, the solvent (acetic acid) was removed by distillation under vacuum. 175 kg of 10% NaOH aqueous solution was added with stirring, after which the resulting mixture was cooled and stirred for 30 minutes. The resulting mixture was discharged into a centrifuge for separation. The resulting cake was dried using a Biconical dryer, yielding 98 kg of 3-methyl-N-nitro-1,3,5,oxadia zinan-4-imine as a white powder (purity 97%, yield 71.5%).

1.2 Preparation of 2-chloro-allyl thioisocyanide 2-chloro-allyl thioisocyanide was prepared using the following reaction scheme: ):.NcI NaSCNTEBA 2,3-dichloropropene 2-chloro-allyl thioisocyanide In a 500 L reactor, 60.5 kg of 2,3-dichioropropene was mixed with 135 kg of toluene, 0.5 kg of TEBA (Triethyl benzyl arumonium chloride, as catalyst) and 44.1 kg of sodium thiocyanate. The resulting mixture was heated under reflux (about 100 to 105t) for 1.5 hours and then cooled to room temperature. 50kg of water was added with stirring for 15 minutes, after which the mixture was allowed to stand and the phases stratify. Toluene from the organic phase was removed under vacuum and the residue was distilled under high vacuum using a Roots Vacuum Pump.

kg of distillate, 2-chloro-allyl thioisocyanid, were recovered as a yellow oil liquid (yield 80%, purity 90%).

1.3 Preparation of 2-chloro-5-(chloromethvl) thiazole 2-chloro-5-(chloromethyl) thiazole was prepared using the following reaction procedure: NCS C12 reflux(77°C) 2-chloro-allyl thioisocyanide 2-chloro-5-(chloromethyl) thiazole 65 kg of 2-chloro-allyl thioisocyanide was mixed with 140 kg of carbon tetrachloride in a 500 [enamel reactor. 35 kg chlorine was bubbled into the mixture over a period of one hour, the resulting mixture heated to reflux (77°C) for 3 hours, and then cooled to room temperature. Carbon tetrachioride was removed by distillation. 59 kg of dichloromethane was added and stirred until the residue was dissolved, after which the solution was washed with 86 kg of saturated NaHCO3 solution and 40 kg of water. The resulting mixture was dried with anhydrous MgSO4, after which dichloromethane was removed by distillation under vacuum. Finally, the reaction product was isolated by distillation under high vacuum using a Roots vacuum pump, to yield 61 kg of 2-chloro-5-(chloromethyl) thiazole as a yellow liquid (yield 84%, purity 96%).

1.4 Preparation of Thiamethoxam Thiamethoxam was prepared by the following reaction scheme:

DMF TEBA

S [ 1 Tulucne (CH3)4N C1 ci ÷ IC,C03 65°C N 2-chloro-5-3-methyl-N-nitro-1 3,5-thiamethoxam (chloromethyl) oxadiazinan-4-imine th I azo I e 47.5 kg of 3-methyl-N-nitro-1,3,5-oxadiazinan-4-imine and 50 kg of 2-chloro-5-(chloromethyl) thiazole were fed to a 1000 L enamel reactor containing 350 kg of dimethyl formamide (DMF). The resulting mixture was heated and the temperature held at about 65°C. Thereafter, 82 kg of potassium carbonate and 1 kg of triethyl benzyl ammonium chloride (TEBA, as catalyst) wore added to the reactor over a period of from 20 to 40 minutes. The resulting mixture was allowed to react for from 4 to 5 hours, after which the mixture was allowed to cool to room temperature.

280 kg of water was added to the reactor, the mixture stirred for 15 minutes and the pH adjusted to between 6 and 7 with 32% hydrochloric acid. The resulting mixture was stirred severely and heated to 65°C. The resulting mixture was allowed to stand for 30 minutes, after which the water phase was discharged and extracted 3 times with dichloromethane (DCM) (100 kg < 3). The organic phases were combined and DCM removed from the mixture by distillation under vacuum. The mixture was dried using a Biconical dryer at 4093, to yield crude thiamethoxam.

Example 2: Preparation of Thiamethoxam Form A 2 g of thiamethoxam as prepared in Example 1 was heated in 10 g of methanol until complete dissolution was achieved. The resulting solution was heated under reflux for 30 to 60 minutes, then cooled to room temperature. The resulting mixture was filtered to isolate a solid. The resulting solid was washed with methanol several times and dried under high vacuum to give crystals of pure thiamethoxam technical (purity: 98%).

The crystals were characterized as being of thiamethoxam Form A using both infrared (iR) spectrometry and x-ray diffracuon.

Form A Lh;amethoxam has the X-ray powder difiractogram shown in Figure 1 with the reflexes listed in Table I below.

Tab!e 1 2 8 and d-value of modification I 28(°) d(A) 6.09 ± 0.2 14.52 ± 0.05 15.37 ± 0.2 5.76 ± 0.03 17.83 ± 0.2 4.98 ± 0.03 18.43 ± 0.2 4.81 ± 0.02 20.86 ± 0.2 4.26 ± 0.02 22.01 ± 0.2 4.04 ± 0.02 26.95 ± 0.2 3.31 ± 0.02 27.84 ± 0.2 3.20 ± 0.02 The IR spectrum of Form A thianiethoxam is set out ri Figure 2. The IF spectrum exhbits characteristic peaks at 2933.62, 2161.78 and 1593.88 cm-i.

Example 3: Preparation of Thiamethoxam Form A 2 g of Thiamethoxam prepared as described in Example 1 and 10 g ot toluene were heated untH complete dissolution was achieved. The resulting mixture was heated under ref Lix for 30 to 60 minutes, then cooled to room temperature. The resulting mixture was I Utered to isolate a sofid. The resulting solid was washed with toluene several times and dried under high vacuum to give crystals of pure thiamethoxam technical (purity: 97%).

The crystals were characterized as being thiamethoxam Form A using infra red spectrometry and x-ray diffraction, as described in Example 2.

Example 4: Preparation of Thiamethoxam Form A 2 g of thiamethoxam prepared as described in Example 1 was dissolved in g of xyiene while applying low heating over a heating plate. The resulting mixture was heated under reflux for 30 to 60 minutess, then cooled to room temperature.

The resulting mixture was filtered to isolate a solid. After filtration, the solid was washed with xylene several times and dried under high vacuum to give crystals of pure thiamethoxani technical (purity: 97%).

The crystals were characterized as being thiamethoxam Form A using infra red spectromeLry and x-ray diffraction, as described in Example 2.

Example 5: Preparation of Thiamethoxam Form A 2 g of thiamethoxam prepared as described in Example 1 and 10 g of ethylene glycol were heated until complete dissolution of the thiamethoxam was reached. The resLilting mixture was heated under reflux for 30 to 60 minutes, then cooled to room temperature. The resulting mixture was filtered to isolate a solid.

After fUtration, the solid was washed with ethylene glycol several times and dried under high vacuum to give crystals of pure thiamethoxam technical (purity: 96%).

Example 6: Preparation of Thiamethoxam Form A 2 g of thiamethoxam as prepared in Example 1 and 10 g of ethanol were heated until complete dissolution of [he thiamethoxarn was achieved. The resulting mixture was heated under reflux for 30 to 60 minutes, then cooled to room temperature. The resulting mixture was filtered to solate a solid. Alter tiltraUon, the solid was washed with ethanol several times and dried under high vacuum to give crystals of pure thiamethoxam technical (purity: 96%).

Example 7: Preparation of Thiamethoxam Form A 2 g of thiamethoxam prepared as described in Example 1 and 10 g of 1 -propanol were heated until complete dissolution of the sohd thiamethoxam was achieved. The resulting mixture was heated under reflux for 30 to 60 minutes, then cooled to room temperature. The resulting mixture was filtered to isolate a solid.

After fUiration, the solid was washed with 1-propanol several times and dried under high vacuum to give crystals ol pure thiamethoxam technical (puriw:97%).

While certain embodiments of the invention have been illustrated and described, it wifl be clear that the invention is not hrnited to the embodiments described herein. Numerous modifications, changes, variations, substitutions and equivalents wifi be apparent to those skflled in the art without departing from the scope of the present invention as described by the claims, which follow.

Claims

CLAIMS1. A crystalline form of 3-(2-chloro-1,3-thiazol-5-ylmethyl)-5-methyl- 1,3,5-oxadiazinan -4-yledene (nitro)amine (thiamethoxam).
2. The crystalline form of claim 1, exhibiting an X-ray powder diffraction pattern having characteristic peaks (expressed in degrees 29+!-0.2° 9) 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.
3. The crystalline form of either of claims 1 or 2, exhibiting an Infrared (IR) spectrum having characteristic peaks at about 2933.62, 2161.78 and 1593.88 cm1.
4. A method for preparing the crystalline form of any preceding claim, comprising crystallizing 3-(2-chloro-1,3-thiazol-5-ylmethy-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 thereof; and isolating the resulting crystals.
5. The method according to claim 4, wherein the solvent is an alcohol, a glycol an aromatic hydrocarbon, or mixtures thereof.
6. The method according to claim 5, wherein the alcohol is methanol, ethanol, or propanol, especially 1-propanol; the glycol is ethylene glycol; and the aromatic hydrocarbon is xylene, or toluene;
7. The method according to any of claims 4 to 6, wherein the solvent system is cooled to a temperature of from 0 to 15°C.
8. The method according to any of claims 4 to 7, wherein the solvent system is seeded with crystals of a crystalline form of 3-(2-chloro-1,3-thiazol-5-ylmethyl)- 5-methyl-i,3,5-oxadiazinan -4-yledene (nitro)amine (thiamethoxam) of any of claims 1 to 3.
9. An insecticide composition comprising a crystalline form of 3-(2-chloro-1,3-thiazol-5-ylmethyl)-5-methyl-1,3,5-oxadiazinan -4-yledene (nitro)amine (thiamethoxam) according to any of claims ito 3.
10. A method for combating insects at a locus, the method comprising applying to the locus a crystalline form of 3-(2-chloro-i,3-thiazol-5-ylmethyl)-5-methyl- 1,3,5-oxadiazinan -4-yledene (nitro)amine (thiamethoxam) according to any of claims 1 to 3 or a composition according to claim 9.
11. The method according to claim 10, wherein the locus is a plant to be protected, a region surrounding a plant to be protected or a seed of a plant to be protected.
12. A method of protecting crops, the method comprising applying to the crops an effective amount of a crystalline form of 3-(2-chloro-1,3-thiazol-5-ylmethyl)- 5-methyl-i,3,5-oxadiazinan -4-yledene (nitro)amine (thiamethoxam) or of a composition according to claim 9.
13. The use of a crystalline form of 3-(2-chloro-1,3-thiazol-5-ylmethyl)-5-methyl-i,3,5-oxadiazinan -4-yledene (nitro)amine (thiamethoxam) according to any of claims 1 to 3 in combating insects.
14. A crystalline form of 3-(2-chloro-1,3-thiazol-5-ylmethyl)-5-methyl- 1,3,5-oxadiazinan -4-yledene (nitro)amine (thiamethoxam) substantially as hereinbefore described having reference to either of Figures 1 or 2.
15. A method for preparing a crystalline form of 3-(2-chloro-1,3-thiazol-5-ylmethyl)- 5-methyl-i,3,5-oxadiazinan -4-yledene (nitro)amine (thiamethoxam) substantially as hereinbefore described.
16. An insecticidal composition comprising a crystalline form of 3-(2-chloro-1,3-thiazol-5-ylmethyl)-5-methyl-1,3,5-oxadiazinan -4-yledene (nitro)amine (thiamethoxam) substantially as hereinbefore described.