HK1145604A - Pesticides and uses thereof - Google Patents

Description

Pesticide and its use

Cross reference to related applications

This application claims priority from U.S. provisional application 60/962,217 filed on 7/27 of 2007, the entire contents of which are incorporated herein by reference.

Technical Field

The invention disclosed in this document relates to the field of pesticides and their use in controlling pests.

Background

Pests cause millions of deaths worldwide each year. In addition, there are more than ten thousand pest species that cause agricultural losses. These agricultural losses amount to billions of dollars each year. Termites (termite) cause damage to various structures such as houses. These termite damage losses amount to billions of dollars each year. It is finally noted that many pests in stored foods (stored foods) eat and adulterate them. These stored food losses amount to billions of dollars each year, but more importantly, deprive people of their food needs.

New insecticides are urgently needed. Insects develop resistance to currently used insecticides. Hundreds of insect species are resistant to one or more insecticides. It is well known to develop resistance to some older insecticides (e.g., DDT, carbamates, and organophosphates). However, resistance has developed even with some newer pesticides. Thus, there is a need for new pesticides, in particular for pesticides with a new mode of action.

Substituents (non-exhaustive list)

The examples given for substituents (other than for halogens) are non-exhaustive and should not be construed as limiting the invention disclosed in this document.

"alkenyl" means a branched or unbranched substituent consisting of carbon and hydrogen which is acyclic and unsaturated (at least one carbon-carbon double bond), for example, vinyl, allyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, and decenyl.

"alkenyloxy" means an alkenyl group further containing a carbon-oxygen single bond, such as allyloxy, butenyloxy, pentenyloxy, hexenyloxy, heptenyloxy, octenyloxy, nonenyloxy, and decenyloxy.

"Alkyloxy" means an alkyl group further containing a carbon-oxygen single bond, such as methoxy, ethoxy, propoxy, isopropoxy, 1-butoxy, 2-butoxy, isobutoxy, t-butoxy, pentyloxy, 2-methylbutyloxy, 1-dimethylpropoxy, hexyloxy, heptyloxy, octyloxy, nonyloxy, and decyloxy.

"alkyl" denotes acyclic, saturated, branched or unbranched substituents consisting of carbon and hydrogen, such as methyl, ethyl, propyl, isopropyl, 1-butyl, 2-butyl, isobutyl, tert-butyl, pentyl, 2-methylbutyl, 1-dimethylpropyl, hexyl, heptyl, octyl, nonyl and decyl.

"alkynyl" means an acyclic, unsaturated (at least one carbon-carbon triple bond and any double bond) branched or unbranched substituent consisting of carbon and hydrogen, for example, ethynyl, propargyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, nonynyl and decynyl.

"alkynyloxy" denotes an alkynyl group further comprising a carbon-oxygen single bond, such as pentynyloxy, hexynyloxy, heptynyloxy, octynyloxy, nonynyloxy and decynyloxy.

"aryl" means a cyclic aromatic substituent consisting of carbon and hydrogen, such as phenyl, naphthyl, and biphenyl.

"cycloalkenyl" means a substituent consisting of carbon and hydrogen which is mono-or polycyclic unsaturated (at least one carbon-carbon double bond), for example cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, cyclodecenyl, norbornenyl, bicyclo [2.2.2] octenyl, tetrahydronaphthyl, hexahydronaphthyl and octahydronaphthyl.

"cycloalkenyloxy" means a cycloalkenyl group further containing a carbon-oxygen single bond, for example, cyclobutenyloxy, cyclopentenyloxy, cyclohexenyloxy, cycloheptenyloxy, cyclooctenyloxy, cyclodecenyloxy, norbornenyloxy and bicyclo [2.2.2] octenyloxy.

"cycloalkyl" means a monocyclic or polycyclic saturated substituent consisting of carbon and hydrogen, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclodecyl, norbornyl, bicyclo [2.2.2] octyl and decahydronaphthyl.

"Cycloalkyloxy" means a cycloalkyl group further containing a carbon-oxygen single bond, for example, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, cycloheptyloxy, cyclooctyloxy, cyclodecyloxy, norbornyloxy and bicyclo [2.2.2] octyloxy.

"halogen" means fluorine, chlorine, bromine and iodine.

"haloalkyl" means alkyl groups further containing from one to the maximum possible number of the same or different halogens, for example fluoromethyl, difluoromethyl, trifluoromethyl, 1-fluoromethyl, 2-fluoroethyl, 2,2, 2-trifluoroethyl, chloromethyl, trichloromethyl and 1, 1, 2, 2-tetrafluoroethyl.

"Heterocyclyl" represents a cyclic substituent which may be fully saturated, partially saturated or fully unsaturated, wherein the cyclic structure contains at least one carbon and at least one heteroatom, wherein the heteroatom is nitrogen, sulfur or oxygen, for example benzofuranyl, benzisothiazolyl, benzisoxazolyl, benzoxazolyl, benzofuranyl (benzoxolyl), benzothienyl, benzothiazolyl, cinnolinyl, furanyl, indolyl, imidazolyl, isoindolyl, isoquinolyl, isothiazolyl, isoxazolyl, 1, 3, 4-oxadiazolyl, oxazolinyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, 1, 2, 3, 4-tetrazolyl, thiazolinyl, thiazolobenzoyloxadiazolyl, thiazolyl, Thienyl, 1, 2, 3-triazinyl, 1, 2, 4-triazinyl, 1, 3, 5-triazinyl, 1, 2, 3-triazolyl and 1, 2, 4-triazolyl.

Disclosure of Invention

The compounds of the invention have the formula

Wherein

R¹Is an unsubstituted heterocyclic group or a substituted heterocyclic group, wherein the unsubstituted heterocyclic group or the substituted heterocyclic group, wherein the substituted heterocyclic group has one or more substituents independently selected from the group consisting of: alkenyl, alkenyloxy, alkyloxy, alkyl, alkynyl, alkynyloxy, aryl, cycloalkenyl, cycloalkenyloxy, cycloalkyl, cycloalkyloxy, halogen, haloalkyl, and heterocyclyl;

R²is H, alkenyl, alkenyloxy, alkyloxy, alkyl, alkynyl, alkynyloxy, aryl, cycloalkenyl, cycloalkenyloxy, cycloalkyl, cycloalkyloxy, halogen, haloalkyl, or heterocyclyl;

R³is H, alkenyl, alkenyloxy, alkyloxy, alkyl, alkynyl, alkynyloxy, aryl, cycloalkenyl, cycloalkenyloxy, cycloalkyl, cycloalkyloxy, halogen, haloalkyl, or heterocyclyl; or

R²And R³May form a ring containing 3 or more ring atoms, said ring optionally including O or N atoms;

R²and R⁴May form a ring containing 3 or more ring atoms, said ring optionally including O or N atoms; or

R⁴Is H, alkenyl, alkenyloxy, alkyloxy, alkyl, alkynyl, alkynyloxy, aryl, cycloalkenyl, cycloalkenyloxy, cycloalkyl, cycloalkyloxy, halogen, haloalkyl, or heterocyclyl; and

R⁵is an unsubstituted heterocyclic group or a substituted heterocyclic group, wherein the substituted heterocyclic group has one or more substituents independently selected from the group consisting of: alkenyl, alkenyloxy, alkyloxy, alkyl, alkynyl, alkynyloxy, aryl, cycloalkenyl, cycloalkenyloxy, cycloalkyl, cycloalkyloxy, halogen, haloalkyl, heterocyclyl, -O- (e.g., as in)、CN、C₁-C₆alkyl-O-C (═ O) -, C₁-C₆alkyl-O-C₁-C₆Alkyl-, C₁-C₆alkylthio-C₁-C₆Alkyl-and NO₂，

Optionally, the substituents on the substituted heterocyclyl (which may be further substituted) are further substituted by one or more substituents independently selected from: alkenyl, alkenyloxy, alkyloxy, alkyl, alkynyl, alkynyloxy, aryl, cycloalkenyl, cycloalkenyloxy, cycloalkyl, cycloalkyloxy, halogen, haloalkyl, heterocyclyl, CN, C₁-C₆alkyl-O-C (═ O) -and NO₂。

In one embodiment of the compounds of the present application, R¹Is a substituted pyridyl group.

In another embodiment, R¹Is substituted pyridyl, which is substituted with one or more halogens.

In another embodiment, R¹Is a substituted pyridyl radical, which is substituted by one or more C₁-C₆Haloalkyl substitution.

In another embodiment, R²Is C₁-C₆An alkyl group.

In another embodiment, R²Is H.

In another embodiment, R²And R⁴Form C₃-C₆An alkyl bridge.

In another embodiment, R³Is H.

In another embodiment, R⁴Is C₁-C₆An alkyl group.

In another embodiment, R⁵Is (mono or poly) substituted or unsubstituted benzothiazolyl, oxazolyl, pyridyl, pyrimidinyl, thiadiazolyl, thiazolyl, thiazolobenzodiazolyl and thienyl, wherein said substituents are independently selected from the group consisting of halogen, NO₂、C₁-C₆Alkyl radical, C₁-C₆Haloalkyl, aryl, benzyl, CN, C₁-C₆alkyl-O-C (═ O) -, C₁-C₆Alkyloxy, -O^-Substituted aryl, C₁-C₆alkyl-O-C₁-C₆Alkyl-, C₁-C₆Cycloalkyl, substituted heterocyclyl, heterocyclyl and C₁-C₆alkylthio-C₁-C₆An alkyl group-.

In another embodiment of the present invention, the substrate is,

R¹is composed of

Wherein Y is alkenyl, alkenyloxy, alkyloxy, alkyl, alkynyl, alkynyloxy, aryl, cycloalkenyl, cycloalkenyloxy, cycloalkyl, cycloalkyloxy, halogen, haloalkyl, and heterocyclyl, and Z is H, halogen, azido, alkyl, alkyloxy, haloalkyl, haloalkyloxy, aryl, or heterocyclyl,

R²is H, alkyl, halogen or haloalkyl;

R³is H, alkyl, halogen or haloalkyl; or

R²And R³May form a ring containing 3 or more ring atoms, said ring optionally including O or N atoms;

R⁴is H, alkyl, halogen or haloalkyl; and

R⁵is an unsubstituted heterocyclic group or a substituted heterocyclic group, wherein the substituted heterocyclic group has one or more substituents independently selected from the group consisting of: alkenyl, alkenyloxy, alkyloxy, alkyl, alkynyl, alkynyloxy, aryl, cycloalkenyl, cycloalkenyloxy, cycloalkyl, cycloalkyloxy, halogen, haloalkyl, and heterocyclyl.

In another embodiment of the present invention, the substrate is,

R¹is composed of

Wherein Y is halogen or C₁-C₄A haloalkyl group;

R²is H, alkyl, halogen or haloalkyl;

R³is H, alkyl, halogen or haloalkyl;

R⁴is C₁-C₄An alkyl group; and

R⁵to have one or more R₆The following groups

Wherein R is₆Is H, halogen haloalkyl or nitro.

In the above embodiments, the number of carbon atoms can vary widely, e.g., C₁-C₂₀、C₁-C₁₀、C₁-C₆、C₁-C₃、C₂-C₂₀、C₂-C₁₀、C₂-C₆、C₃-C₆、C₃-C₈And each number within these ranges.

These compounds may be prepared by any method known in the art, examples of which are shown below.

Detailed Description

Examples

The examples are for illustrative purposes and should not be construed as limiting the invention disclosed in this document to only the embodiments disclosed in these examples.

Example I:3- [ 1-Ethyl (N- ((5-fluoro) pyridin-2-yl) -sulfoximinyl) (methyl)]-6-trifluoromethyl Preparation of pyridine (1)

To a magnetically stirred suspension of 6.9g (0.05mol) anhydrous potassium carbonate in 20ml freshly distilled pyrrolidine was added 11.8g (0.01mol) of 3-methylthiobutyraldehyde dropwise over 10 minutes at-5 ℃ under nitrogen. The reaction mixture was warmed to room temperature over 3 hours and then filtered through a sintered glass funnel, washing the residue thoroughly with 150ml of anhydrous ether. After removal of the solvent on a rotary evaporator, Kugelif distillation (Kugelrohr distillation) was carried out at 90-95 ℃ C./1 mm to give 1-pyrrolidinyl-3-methylthio-1-butene (A) as an almost colorless liquid with a yield of 96%.

To a magnetically stirred solution of 1.68g (0.01mol) of (E) -4-ethoxy-1, 1, 1-trifluoro-but-3-en-2-one (EFTBO) in 10ml of dry ether was added dropwise a solution of 1.71g (0.01mol) of 1-pyrrolidinyl-3-methylsulfanyl-1-butene (A) in 2ml of ether at-5 ℃ under nitrogen over 2 minutes. The reaction mixture was warmed to room temperature over 3 hours, which turned yellow. After removal of the solvent on a rotary evaporator, 10ml of Dimethylformamide (DMF) and 1.54g (0.02mol) of ammonium acetate are added. The reaction mixture was heated to 100 ℃ and held for 2 hours, allowed to cool to room temperature, and then added to 100ml of diethyl ether and 25ml of saturated NaCl. The organic layer was washed with 3X 25ml of saturated NaCl and dried (MgSO)₄) Then, the solvent was removed to obtain 1.75g of an orange oil. Column chromatography, eluting with 5% EtOAc in hexanes, afforded 2-trifluoromethyl-5- (1-methylsulfanyl) ethylpyridine (B) in 41.4% yield.¹H NMR 1.62(d, 3H, J ═ 7), 1.94(s, 3H), 3.93(q, 1H, J ═ 7), 7.67(d, 1H, J ═ 8.2), 7.89(dd, 1H, J ═ 8.2, 1.8), 8.66(d, 1H, J ═ 1.8). For C₉H₁₀F₃Calculated value of NS: c, 48.86; h, 4.56; n, 6.33: and S, 14.49. And (3) observation value: c, 49.43; h, 4.69;N，5.97：S，15.47。

to a solution of 2-trifluoromethyl-5- (1-methylsulfanyl) ethylpyridine (B) (10g, 45mmol) in acetonitrile (350mL) was added chloramine-T (13.4g, 47 mmol). The mixture was stirred overnight, then ethyl acetate (200mL) was added. The crude reaction mixture was then passed through a plug of silica gel (acetone eluent) and concentrated to give the sulfilimine (C) as a white fluffy solid in 40% yield. LC-MS (ESI): for C₁₆H₁₇F₃N₂O₂S₂Calculated value of [ M ]]⁺390, observed value 390.

To NaIO at 25 deg.C₄(2.2g, 10mmol) in H₂To the solution in O (18mL) was added CH sequentially₂Cl₂(18mL) and RuCl₃(29mg, 0.13 mmol). Thioimine (C) (2.0g, 5.1mmol) was then added to the dark brown mixture in CH₂Cl₂(16 mL). The mixture was stirred for 3h, then stirring was stopped and the reaction mixture was allowed to stand until the layers were defined. The organic layer was removed and then filtered through a porous funnel filled with sand and alumina and celite (acetone eluent). The filtrate was concentrated to give sulfoximine (D) as a white solid in 40% yield. LC-MS (ESI): for C₁₆H₁₈F₃N₂O₃S₂Calculated value of [ M + H ]]⁺407, observation 407.

Sulfoximine (D) (1.0g, 2.5mmol) was dissolved in concentrated H₂SO₄(15mL) and then stirred for 6 h. The crude reaction mixture was then poured into a flask containing ice and solid NaHCO was slowly added₃Until the aqueous layer became neutral. CH for aqueous layer₂Cl₂Extracting, and collecting the organic extracts over MgSO₄Drying and concentrating to obtain 5- [1- (methylsulfonyl) ethyl]-2-trifluoromethylpyridine (E) as a white solid in 84% yield. LC-MS (ESI): for C₉H₁₁F₃N₂Calculated value of OS [ M]⁺252, observation 252.

To a mixture of palladium (II) acetate (7mg, 0.03mmol) and rac-2, 2 '-bis (diphenylphosphino) -1, 1' -binaphthyl (30mg, 0.05mmol) in toluene (3mL) was added 2-bromo-5-fluoropyridine (119mg, 0.67mmol), 5- [1- (methylsulfonoximido) ethyl]-2-trifluoromethylpyridine (E) (200mg, 0.8mmol) and cesium carbonate (310mg, 0.95 mmol). The mixture was heated to 110 ℃ overnight, then the crude reaction mixture was filtered through celite, concentrated, and purified by column chromatography (40% acetone/60% hexane) to give 3- [ 1-ethyl (N- ((5-fluoro) pyridin-2-yl) -sulfoximinyl) (methyl)]6-trifluoro-methylpyridine (1) as an orange oil in 52% yield as a 1: 1 mixture of diastereomers.¹H NMR(400MHz，CDCl₃) δ (mixture of diastereomers) 8.79(d, 1H), 8.78(d, 1H), 8.02-8.09(m, 4H), 7.74(d, 1H), 7.72(d, 1H), 7.24-7.29(m, 2H), 6.78(dd, 1H), 6.72(dd, 1H), 5.16(q, 1H), 5.07(q, 1H), 3.14(s, 3H), 3.06(s, 3H), 1.92(d, 3H), 1.89(d, 3H); LC-MS (ESI): for C₁₄H₁₃F₄N₃Calculated value of OS [ M]⁺348, observed value 348.

Example II:3- [ 1-Ethyl (N- ((5-chloro) pyridin-2-yl) -sulfoximinyl) (methyl)]-6-IIIFluoromethyl radical Preparation of pyridine (2)

To a mixture of palladium (II) acetate (2mg, 0.01mmol) and rac-2, 2 '-bis (diphenylphosphino) -1, 1' -binaphthyl (7.5mg, 0.01mmol) in toluene (1mL) was added 2-chloro-5-fluoropyridine (32mg, 0.17mmol), 5- [1- (methylsulfonoximido) ethyl]-2-trifluoromethylpyridine (E) (50mg, 0.2mmol) and cesium carbonate (77mg, 0.24 mmol). The mixture was heated in a microwave at 150 ℃ for 30 minutes, and then the crude reaction mixture was treated with CH₂Cl₂Diluted (1mL), filtered through celite, concentrated and chromatographed on a column (SiO)₂40% acetone/60% hexane) to give 3- [ 1-ethyl (N- ((5-chloro) pyridin-2-yl) -sulfoximinyl) (methyl)]6-Trifluoromethylpyridine (2) as an orange oil in 99% yield as a 1: 1 mixture of diastereomers.¹H NMR(400MHz，CDCl₃) δ (mixture of diastereomers) 8.75-8.80(m, 2H), 8.06-8.15(m, 4H), 7.74(m, 2H), 7.48(dd, 1H), 7.45(dd, 1H), 6.76(d, 1H), 6.70(d, 1H), 5.18(q, 1H), 5.08(q, 1H), 3.16(s, 3H), 3.08(s, 3H), 1.93(d, 3H), 1.90(d, 3H); LC-MS (ESI): for C₁₄H₁₄ClF₃N₃Calculated value of OS [ M + H]⁺And 365, observed value 365.

Example III:3- [ 1-Ethyl (N- ((4-fluoro) pyridin-2-yl) -sulfoximinyl) (methyl)]-6-trifluoromethyl Preparation of phenylpyridine (3)

To a solution of toluene (3ml), palladium (II) acetate (0.007g, 0.032mmol) and rac-2, 2 '-bis (diphenylphosphino) -1, 1' -binaphthyl (0.029g, 0.048mmol) was added 5- [1- (methylsulfonoxime)Yl) ethyl]-2-trifluoromethylpyridine (E) (0.2g, 0.793mmol), 2-bromo-4-fluoropyridine (0.088g, 0.674mmol), cesium carbonate (0.309g, 0.951mol) and triethylamine (0.110ml, 0.793 mmol). The reaction mixture was heated in a microwave at 180 ℃ for 510 seconds. The solution was concentrated to dryness, the dark solid was suspended in water and then extracted with EtOAc (3 × 100 ml). Combine the EtOAc layers and dry (MgSO)₄) Filtered and concentrated to dryness. The crude product was purified by silica gel column chromatography (eluent: 50-60% EtOAc/hexane) to give 3- [ 1-ethyl (N- ((4-fluoro) pyridin-2-yl) -sulfoximinyl) (methyl)]-6-trifluoromethyl-pyridine (3) 3: 2 mixture of diastereoisomers as yellow oil (0.036g, 15%).¹H NMR(δ，CDCl₃)：8.8(m，2H)，8.1(m，4H)，7.7(m，2H)，6.5(m，4H)，5.1(m，2H)，3.2(s，3H)，3.1(s，3H)，1.9(m，6H)；M+2H＝349.2.

TABLE 1 Compounds

A ═ the pathway used in example I; b ═ the pathway used in example II; c ═ the route used in example III.

Example IV:5- {1- [ methyl (4-)Methylphenyl) -1, 3-thiazol-2-yl) sulfoximinyl]Second step Preparation of 2- (trifluoromethyl) pyridine (19) yl

5- {1- [ methyl (4-bromo-1, 3-thiazol-2-yl) sulfoximinyl]Ethyl } -2- (trifluoromethyl) pyridine (13) (0.055g, 0.133mmol), 4-methylphenylboronic acid (0.027g, 0.199mmol) and tetrakis (triphenylphosphine) palladium (0) (0.006g, 0.005mmol) in dioxane (0.9ml) and 2M Na₂CO₃(0.070g in 0.33ml water) the suspension was heated under reflux for 2 hours. The reaction mixture was cooled and filtered. The filtrate was evaporated in vacuo and the residue was dissolved in EtOAc, followed by washing with water and brine. The combined organic layers were dried (MgSO)₄) Filtered and concentrated to dryness. Subjecting the crude product to column chromatography (SiO)₂Eluted with a gradient of 50% EtOAc/hexanes) to give 5- {1- [ methyl (4- (4-methylphenyl) -1, 3-thiazol-2-yl) sulfoximinyl]Ethyl } -2- (trifluoromethyl) pyridine (19) as a dark yellow semisolid (0.039g, 70%). A 1: 1 mixture of two diastereomers.¹H NMR(300MHz，CDCl₃)8.85(d, 1H), 8.75(d, 1H), 8.1(m, 2H), 7.7(m, 6H), 7.2(m, 4H), 6.9(d, 2H), 5.4(m, 1H), 5.2(m, 1H), 3.3(s, 3H), 3.1(s, 3H), 2.4(d, 6H), 2.0(d, 3H), 1.9(d, 3H); LC-MS (ESI): for C₁₉H₁₈F₃N₃OS₂Calculated value of [ M + H ]]⁺And 426, observation 426.

TABLE 2 Compounds

D ═ the route used in example IV

Example V:3- [ 1-Ethyl (N- (1-oxy-pyridin-2-yl) -sulfoximinyl) (methyl)]-6-trifluoromethyl Preparation of phenylpyridine (24)

To 3- [ 1-ethyl (N- (2-pyridine) -sulfoximinyl) (methyl)]-6-trifluoromethylpyridine (4) (100mg, 0.3mmol) in CHCl₃To the solution (2mL) was added m-chloroperoxybenzoic acid (mCPBA) (70% purity, 105mg, 0.6 mmol). The solution immediately changed from orange to yellow upon addition. After 1h, the crude reaction mixture was taken up with aqueous sodium bisulfite and NaHCO₃The aqueous solution was washed, dried and concentrated to give 3- [ 1-ethyl (N- (1-oxy-pyridin-2-yl) -sulfoximinyl) (methyl)]-6-trifluoro-methylpyridine (24) as a yellow solid in 23% yield as a 1: 1 mixture of diastereomers. Mp is 43-47 deg.C;¹H NMR(400MHz，CDCl₃) δ (mixture of diastereomers) 8.86(dd, 2H), 8.20(dd, 1H), 8.06-8.12(m, 3H), 7.73(d, 2H), 7.09-7.15(m, 2H), 6.98(dd, 1H), 6.89(dd, 1H), 6.79-6.85(m, 2H), 5.21(q, 1H), 5.11(q, 1H), 3.36(s, 3H), 3.33(s, 3H), 1.99(d, 3H), 1.95(d, 3H); LC-MS (ESI): for C₁₄H₁₅F₃N₃O₂Calculated value of S [ M + H]⁺346, observed value 346.

Example VI:3- [ 1-Ethyl (N- (benzothiazol-2-yl) -sulfoximinyl) (methyl)]-6-trifluoromethyl Preparation of pyridine (25)

To a solution of 5- (1-methylsulfanyl-ethyl) 2-trifluoromethylpyridine (0.5g, 2.25mmol) and 2-benzothiazole (0.37g, 2.48mmol) in dichloromethane (8ml) cooled to-25 ℃ was slowly added N-chlorosuccinamide (0.33g, 2.48mmol) while maintaining the internal temperature of the reaction mixture between-22 ℃ and-28 ℃. The reaction mixture was slowly warmed to room temperature and then stirred for an additional hour. The reaction mixture was washed with water and the dichloromethane layer was dried (MgSO)₄) Filtered and concentrated to dryness. The crude product was purified by silica gel column chromatography (eluent: 50% EtOAc/hexane, 100% EtOAc) to give 3- [ 1-ethyl (N- (2-benzothiazole) -sulfinyl) (methyl)]-6-trifluoromethylpyridine (F) as a yellow solid (0.37g, 45%); m + H371.1.

To a solution of 77% mCPBA (0.34g, 1.5mmol) in EtOH (5ml) was added a solution of potassium carbonate (0.42g, 3.0mmol) in water (5ml) at 0 deg.C and then stirred for 20 min. To this was added 3- [ 1-ethyl (N- (2-benzothiazole) -sulfinyl) (methyl)]A solution of-6-trifluoromethylpyridine (F) (0.37g, 1.0mmol) in EtOH (5ml) was then stirred at 0 ℃ for 1 hour. The reaction mixture was concentrated to dryness, and a white solid was suspended in dichloromethane (100ml) and filtered to remove the solid. The filtrate was collected and concentrated to dryness. The crude product was purified by silica gel column chromatography (eluent: 30-50% EtOAc/hexane) to give 3- [ 1-ethyl (N- (2-benzothiazole) -sulfoximinyl) (methyl)]A mixture of the 3: 2 diastereoisomers of 6-trifluoromethylpyridine (25) as a yellow semisolid (0.073g, 18%).¹H NMR(δ，CDCl₃)：8.81(d，1H)，8.79(d，1H)，8.1(m，2H)，7.7(m，6H)，7.3(m，4H)，5.3(m，2H)，3.3(s，3H)，3.2(s，3H)，2.0(m，6H)。

Example VII:3- [ 1-Ethyl (N- ((4)-trifluoromethyl) thiazol-2-yl) -sulfoximinyl) (methyl)]-6- Preparation of trifluoromethylpyridine (26)

To a solution of 5- (1-methylsulfanyl-ethyl) 2-trifluoromethylpyridine (0.5g, 2.25mmol) and 2-amino-4-trifluoromethylthiazole (0.42g, 2.48mmol) in dichloromethane (8ml) cooled to-25 ℃ was slowly added N-chlorosuccinamide (0.33g, 2.48mmol) while maintaining the internal temperature of the reaction mixture between-22 ℃ and-28 ℃. The reaction mixture was slowly warmed to room temperature and then stirred for an additional hour. The reaction mixture was washed with water and the dichloromethane layer was dried (MgSO)₄) The crude product was purified by column chromatography over silica gel (eluent: 50% EtOAc/hexanes, 100% EtOAc) to afford 3- [ 1-ethyl (N- ((4-trifluoromethyl) thiazol-2-yl) -sulfinyl) (methyl)]-6-trifluoromethylpyridine (G) as a yellow solid (0.81G, 93%); m + H288.1.

To a solution of 77% mCPBA (0.69g, 3.14mmol) in EtOH (5ml) at 0 deg.C was added K₂CO₃(0.87g, 6.3mmol) in water (5ml) and then stirred for 20 minutes. To this was added 3- [ 1-ethyl (N- ((4-trifluoromethyl) thiazol-2-yl) -sulfinyl) (methyl)]A solution of-6-trifluoromethylpyridine (G) (0.81G, 2.1mmol) in EtOH (5ml) was then stirred at 0 ℃ for 1 hour. The reaction mixture was concentrated to dryness, and a white solid was suspended in dichloromethane (100ml) and filtered to remove the solid. The filtrate was collected and concentrated to dryness. The crude product was purified by silica gel column chromatography (eluent: 30-50% EtOAc/hexane) to give 3- [ 1-ethyl (N- ((4-trifluoromethyl) thiazol-2-yl) -sulfoximinyl) (methyl)]-a 3: 2 diastereomer mixture of 6-trifluoromethylpyridine (26),it was a yellow semisolid (0.073g, l 8%).¹H NMR(δ，CDCl₃)：8.6(d，1H)，8.6(d，1H)，8.1(m，2H)，7.7(m，2H)，7.1(m，2H)，5.1(m，2H)，3.3(s，3H)，3.2(s，3H)，1.9(m，6H)；M+H＝404.1。

Example VIII:5- {1- [ methyl (4- (4-fluorophenyl) -1, 3-thiazol-2-yl) sulfoximinyl]Second step Preparation of 2- (trifluoromethyl) pyridine (27)

[1- (6-trifluoromethylpyridin-3-yl) ethyl group](methyl) -oxy-lambda⁴Thioiminonitrile (H) was prepared as described in patent WO2007095229 (example II). Stirring sulfoximine (H) (5.0g, 18mmol) in CH at 0 deg.C₂Cl₂Trifluoroacetic anhydride (7.5mL, 54mmol) in solution (300 mL). The mixture was allowed to react at room temperature until the starting material was completely consumed (monitored by TLC for 2 h). The reaction mixture was concentrated in vacuo, dissolved in methanol (125mL) and then washed with K₂CO₃(12.5g, 90 mmol). The mixture was stirred at room temperature until consumption of starting material (monitored by TLC for 2 h). The crude reaction mixture was filtered, concentrated, and purified by chromatography (acetone: hexane) to give 5- [1- (methylsulfonoximido) ethyl]-2-trifluoromethylpyridine (E) as a white solid (3.5g, 77%).¹HNMR (400MHz, acetone-D)₆) δ (mixture of diastereomers) 8.9(s, 1H), 8.2(m, 1H), 7.9(d, 1H), 4.6(q, 1H), 2.8(s, 3H), 1.8(d, 3H); LC-MS (ESI): observed value [ M]⁺252. For C₉H₁₁F₃N₂The calculated OS is 252.

In a 50mL Round Bottom Flask (RBF) equipped with a magnetic stir bar,5- [1- (methylsulfonoximido) ethyl at room temperature]-2-trifluoromethylpyridine (E) (0.236g, 0.937mmol) was dissolved in 5: 1 THF: DMF (21 mL). Isothiocyanate (0.368g, 1.31mmol) was then added to the reaction flask, and the reaction mixture was warmed to 80 ℃ and held for 12 h. Once the addition was complete, the mixture was poured into a separatory funnel and diluted with EtOAc followed by brine. The aqueous layer was extracted with EtOAc. The organics were combined, washed with brine, over anhydrous Na₂SO₄Dried, filtered and then concentrated in vacuo. The crude material was purified by chromatography to give sulfoximine (I) as a yellow solid (0.297g, 59%).¹H NMR(400MHz，CDCl₃) Delta (mixture of diastereomers) 8.84(s, 1H), 8.36(q, 1H), 8.22(d, 1H), 7.69(q, 4H), 7.75(t, 1H), 7.43(t, 2H), 7.34(t, 2H), 5.04& 4.80(m，1H)，4.49 & 4.26(m，3H)，3.50 &3.43(s, 3H), 1.97(m, 3H); LC-MS (ESI): observed value [ M + H]⁺534. For C₂₅H₂₂F₃N₃O₃S₂533.

In 5mL RBF equipped with a magnetic stir bar, sulfoximine (I) (0.100g, 0.187mmol) was dissolved in 2mL piperidine/DMF at room temperature while stirring. Once the addition was complete, the mixture was concentrated in vacuo. The crude material was purified by chromatography to give thiourea (J) as an off-white solid (0.043g, 74%).¹H NMR(400MHz，CDCl₃) Delta (mixture of diastereomers) 8.86(s, 1H), 8.10(m, 1H), 7.76(m, 1H), 6.09& 5.94(m，1H)，3.52 &3.24(s, 3H), 1.88(d, 3H); LC-MS (ESI): observed value [ M + H]⁺312.1. For C₁₀H₁₂F₃N₃OS₂The calculated value of (a) is 311.

To a suspension of sulfoximine (J) (50mg, 0.2mmol) in ethanol (1mL) was added bromo-4-fluoroacetophenone (40 μ L, 0.2mmol), and the reaction mixture was stirred at 70 ℃ for 4 h. The reaction mixture was then concentrated and then purified by chromatography to give 5- {1- [ methyl (4- (4-fluorophenyl) -1, 3-thiazol-2-yl) sulfooximino]Ethyl } -2- (trifluoromethyl) pyridine (27) as a white solid 29mg (42%). mp is 89-94 ℃.¹H NMR(400MHz，CDCl₃) δ (1: 1 mixture of two diastereomers) 8.83(s, 1H), 8.77(s, 1H), 8.11(m, 2H), 7.73-7.80(m, 6H), 7.05-7.11(m, 4H), 6.86(d, 2H), 5.28(q, 1H), 5.17(q, 1H), 3.28(s, 3H), 3.17(s, 3H), 2.00(d, 3H), 1.94(d, 3H); LC-MS (ESI): for C₁₈H₁₆F₄N₃OS₂Calculated value of [ M +1 ]]⁺430, observation 430.

TABLE 3 Compounds

E ═ the pathway used in example VIII

Example IX.5- { [ methyl [4- (4-methoxyphenyl) -1, 3-thiazol-2-yl]Sulfo oxime radical]First of all Preparation of yl } -2- (trifluoromethyl) pyridine (54):

to a dry 1L round bottom flask equipped with a magnetic stir bar, dropping funnel, thermometer and nitrogen inlet was added potassium carbonate (33.2g, 240mmol) and pyrrolidine (136.5g, 160mL, 1.92mol) and the resulting suspension was cooled to 0 ℃ in an ice bath. 3- (methylthio) propanal (K) (50g, 480mmol) was added dropwise through a dropping funnel at a rate to maintain the reaction temperature at 0-7 ℃. The resulting pale yellow mixture was warmed to room temperature and stirred for 16 hours. The residual potassium carbonate is removed by filtration and the filter cake is taken up in Et₂O wash and concentrate the filtrate on a rotary evaporator to give the crude enamine as a viscous light yellow oil. Fractional distillation (108 ℃ C., 110 ℃ C., 4mm Hg) gave 63.3g (83.8%) of 1- [3- (methylthio) prop-1-enyl]Pyrrolidine (L) as a colorless liquid.¹H NMR(CDCl₃)δ6.29(d，1H)，4.06(dt，1H)，3.16(d，2H)，3.03(m，4H)，2.04(s，3H)，1.85(m，4H).GC-MS(EI)m/z157(M⁺)。

To a dry 1L round bottom flask equipped with a magnetic stir bar, dropping funnel, thermometer and nitrogen inlet was added 4-ethoxy-1, 1, 1-trifluorobut-3-en-2-one (M) (67.4g, 401mmol) and 133ml anhydrous acetonitrile, and the resulting solution was cooled to 0 ℃ in an ice bath. To this solution was added dropwise 1- [3- (methylthio) prop-1-enyl ] group through a dropping funnel]Pyrrolidine (L) (63.0g, 401mmol, solution in 50ml of anhydrous acetonitrile) was added dropwise at a rate to maintain the reaction temperature at 0-7 ℃. The ice bath was removed and the resulting dark red (burgundy) solution was warmed to room temperature and stirred for 2 hours. Ammonium acetate (46.3g, 601mmol) was added and then the reaction mixture was heated to reflux and stirred for 5 hours, then stirred at room temperature for 16 hours. Acetonitrile was evaporated on a rotary evaporator and the residue was dissolved in 1LEt₂In O, washed with water (3X 200mL) and dried (Na)₂SO₄) Filtered and then Et-removed on a rotary evaporator₂O, 83.4g of crude pyridine was obtained as a dark red oil. Performing flash chromatography (SiO)₂25 → 70% EtOAc/hexane) to yield 70.8g (85%) of 5- [ (methylthio) methyl group]-2- (trifluoromethyl) pyridine (N) as an orange oil.¹H NMR(CDCl₃)δ8.64(d，1H)，7.86(dd，1H)，7.66(d，1H)，3.73(s，2H)，2.02(s，3H).GC-MS(EI)m/z 207(M⁺)。

To a dry 1L round bottom flask equipped with a magnetic stir bar and nitrogen inlet was added 5- [ (methylthio) methyl group]-2- (trifluoromethyl) pyridine (N) (50.0g, 241mmol), cyanamide (10.1g, 241mmol) and 500ml anhydrous acetonitrile, and the resulting solution was then cooled to 0 ℃ in an ice bath. Iodobenzene diacetate (77.7g, 241mmol) was added all at once and the resulting yellow-orange mixture was mixedThe mixture was warmed to room temperature and stirred for 16 hours. The reaction mixture was washed with hexane (4X 200mL) and then concentrated on a rotary evaporator to give 78.3g of crude thioimine as an orange oil. The oil was washed with warm hexane (55 deg.C) and then dissolved in CH₂Cl₂(650 mL). The resulting orange precipitate was removed by vacuum filtration and the filtrate was concentrated on a rotary evaporator to give thioimine (O) as an orange oil, which was used without further purification.

Thioiimine intermediate (O) (59.6g, 241mmol) was dissolved in 250ml CH₂Cl₂Then, the solution was added dropwise to a 2L round-bottom flask equipped with a magnetic stirrer bar, a dropping funnel, a thermometer and a nitrogen inlet, the flask being previously charged with sodium periodate (77.3g, 362mmol), water (500mL), CH₂Cl₂(500mL) and ruthenium-H chloride₂O (1.36g, 6.0 mmol). The two-phase system was stirred vigorously at room temperature for 16 hours, and the resulting light brown mixture was then filtered through a buchner funnel. The filtrate was transferred to a separatory funnel and the phases were separated. CH for aqueous solutions₂Cl₂(2X 200mL) and the combined organic extracts were washed with water (2X 250mL) and dried (Na)₂SO₄) And filtering. The dark solution was treated with neutral alumina (150g) and then stirred at room temperature for 15 minutes. The alumina was removed by filtration and the resulting colorless solution was concentrated on a rotary evaporator to give the crude product as a viscous pale yellow solid. With Et₂O trituration to give 13.1g (21%) methyl (oxy) { [6- (trifluoromethyl) pyridin-3-yl]Methyl } -lambda⁴Sulfoximine (P), which is a granular white solid. Mp 137-.¹H NMR(DMSO-d₆)δ8.83(s，1H)，8.20(dd，1H)，8.05(d，1H)，5.27(s，2H)，3.49(s，3H)。LC-MS(ESI)m/z 264[M+H]⁺，m/z 262[M-H]^-。

Compound (Q) is as described in example VIIIThe operation of (2) is synthesized. Isolated as a white solid. Mp 108-.¹H NMR(DMSO-d₆)δ8.76(d，1H)，8.13(dd，1H)，7.96(d，1H)，4.58(q，2H)，3.92(s，1H)，2.85(s，3H).LC-MS(ESI)m/z 239[M+H]⁺，m/z 237[M-H]^-。

Compound (R) was synthesized according to the procedure described in example VIII. A pale yellow foam was isolated. Mp 92-97 ℃.¹H NMR(DMSO-d₆)δ11.18(s，1H)，8.93(s，1H)，8.29(d，1H)，7.98(d，1H)，7.91(d，2H)，7.83(d，2H)，7.43(t，2H)，7.34(dt，2H)，5.21(d，2H)，4.33-4.24(m，3H)，3.66(s，3H).LC-MS(ESI)m/z 520[M+H]⁺，m/z 518[M-H]^-。

Compound (S) was synthesized according to the procedure described in example VIII. Isolated as a white solid. Mp 107-.¹H NMR(CDCl₃)δ8.82(s，1H)，8.11(d，1H)，7.76(d，1H)，6.36(bs，1H)，6.19(bs，1H)，5.52(d，1H)，5.06(d，1H)，3.39(s，3H).LC-MS(ESI)m/z298[M+H]⁺，m/z 296[M-H]^-。

5- { [ methyl [4- (4-methoxyphenyl) -1, 3-thiazol-2-yl]Sulfo oxime radical]Methyl } -2- (trifluoromethyl) pyridine (54) was synthesized according to the procedure described in example VIII. Isolated as a foamy white solid. Mp 158-.¹H NMR(CDCl₃)δ8.73(d，1H)，7.99(dd，1H)，7.76(d，2H)，7.74(d，1H)，6.92(dd，2H)，6.83(s，1H)，5.09(d，1H)，5.01(d，1H)，3.84(s，3H)，3.24(s，3H).LC-MS(ESI)m/z 428[M+H]⁺，m/z 426[M-H]^-。

TABLE 4 Compounds

F ═ the route used in example IX

Example X.5- { [ methyl [4- (4-methoxyphenyl) -1, 3-thiazol-2-yl]Sulfo oxime radical]Methyl } -2- Preparation of chloropyridine (57):

compound (V) was synthesized according to the procedure described in example VIII. Isolated as a white solid. Mp 132-.¹H NMR(DMSO-d₆)δ8.43(d，1H)，7.90(dd，1H)，7.56(d，1H)，4.48(d，1H)，4.41(d，1H)，3.83(s，1H)，2.81(s，3H)。LC-MS(ESI)m/z 203[M-H]^-。

Compound (W) was synthesized according to the procedure described in example VIII. A pale yellow foam was isolated. Mp 98-101 ℃.¹H NMR(DMSO-d₆)δ11.15(s，1H)，8.56(d，1H)，8.05(dd，1H)，7.90(d，2H)，7.84(d，2H)，7.59(d，1H)，7.44(t，2H)，7.34(dt，2H)，5.09(s，2H)，4.32-4.26(m，3H)，3.61(s，3H)。LC-MS(ESI)m/z 486[M+H]⁺，m/z 484[M-H]^-。

Compound (X) was synthesized according to the procedure described in example VIII. Isolated as a light orange solid. Mp 155-.¹H NMR(DMSO-d₆)δ8.51(d，1H)，8.12(bs，1H)，7.99(d，1H)，7.96(d，1H)，7.61(d，1H)，5.21(s，2H)，3.36(s，3H)。LC-MS(ESI)m/z 264[M+H]⁺，m/z 262[M-H]^-。

5- { [ methyl [4- (4-methoxyphenyl) -1, 3-thiazol-2-yl]Sulfo oxime radical]Methyl } -2-chloropyridine (57) was synthesized according to the procedure described in example VIII. Isolated as a pale yellow solid. Mp 160-.¹H NMR(CDCl₃)δ8.39(d，1H)，7.78-74(m，3H)，7.38(d，1H)，6.92(d，2H)，6.82(s，1H)，4.94(s，2H)，3.84(s，3H)，3.21(s，3H)。LC-MS(ESI)m/z 394[M+H]⁺，m/z 392[M-H]^-。

TABLE 5 Compounds

G-route used in example X

Example XI.5- {1- [ methyl (4- (4-methoxybenzene)1, 3-thiazol-2-yl) -1, 3-thiazol-2-yl) sulfoximinyl]Wu Ying (five-element) Preparation of yl } -2- (trifluoromethyl) pyridine (60):

5- { [ methyl [4- (4-methoxyphenyl) -1, 3-thiazol-2-yl ] magnetically stirred at-78 deg.C]Sulfo oxime radical]To a solution of methyl } -2- (trifluoromethyl) pyridine (54) (0.125g, 0.29mmol) in anhydrous THF (2mL) was added n-butyllithium (0.13mL of a 2.5M solution in hexane, 0.32mmol), and the resulting orange solution was stirred at-78 deg.C for 20 minutes. Methyl iodide (0.046g, 0.32mmol) was added and the reaction mixture was then warmed to room temperature. LC-MS analysis showed that only 13% of the desired monomethyl intermediate was formed. The reaction mixture was cooled to-78 deg.C, another batch of n-butyllithium (0.13ml of a 2.5M solution in hexane, 0.32mmol) was added, and the reaction mixture was stirred for 20 minutes. Another charge of iodomethane (0.046g, 0.32mmol) was added and the reaction mixture was warmed to room temperature. LC-MS showed the formation of 65% of the desired mono-methyl compound, and 35% of the mono-butyl compound, which is produced from butyl iodide produced by the reaction of n-butyl lithium with methyl iodide. The reaction mixture was quenched with aqueous ammonium chloride, extracted with EtOAc (2X 10mL), and the organic extracts were dried (Na)₂SO₄) Filtered and concentrated to give an orange oil. Performing flash chromatography (SiO)₂0 to 100% EtOAc/hexanes) to yield 24mg of 5- {1- [ methyl (4- (4-methoxyphenyl) -1, 3-thiazol-2-yl) sulfoximinyl]A 55: 45 mixture of two diastereomers of pentyl } -2- (trifluoromethyl) pyridine (60) as an orange oil.¹H NMR(CDCl₃)δ8.80(s，0.45H)，8.73(s，0.55H)，8.11(t，1H)，7.78-7.72(m，3H)，6.96-6.87(m，2H)，6.81(s，0.45H)，6.78(s，0.55H)，5.26-5.21(m，0.45H)，4.96-4.91(m，0.55H)，3.85(s，1.4H)，3.84(s，1.6H)，3.27(s，1.5H)，3.10(s，1.4H)，2.51-2.04(m，2H)，1.43-1.14(m，4H)，0.92-0.79(m，3H).LC-MS(ESI)m/z 484[M+H]⁺，m/z 482[M-H]^-。

Example XII.5- {1- [ (5-benzyl-1, 3-thiazol-2-yl) (methyl) sulfoximinyl group]Ethyl } -2- (tris) Preparation of fluoromethyl) pyridine (61):

(1) preparation of 2-bromo-3-phenylpropanal: dibromobarbituric acid (1.43g, 5mmol) was dissolved in diethyl ether (40mL) and phenylpropionaldehyde (1.34g, 1.33mL, 10mmol) was added. After stirring at room temperature for 5 days, a precipitate of barbituric acid was observed. The reaction mixture was filtered and then saturated NaHCO₃(1X 40mL) and brine (2X 40 mL). The mixture is passed over Na₂SO₄Drying, filtering and removing the solvent under reduced pressure. GC-MS analysis of the concentrate showed 2-bromo-3-phenylpropionaldehyde to be the only product. (2) Preparation of (61): n- (methyl (oxo) {1- [6- (trifluoromethyl) -pyridin-3-yl)]Ethyl } -lambda⁶Thienylene) thiourea (J) (100mg, 0.321mmol) was suspended in EtOH (1mL) and a solution of 2-bromo-3-phenylpropionaldehyde (82mg, 0.385mmol, 1.2 equiv.) in EtOH (0.6mL) was added. The reaction mixture was stirred at room temperature for 1h, then heated to reflux and held for 30 min. The solvent was removed under reduced pressure and the residue was purified by preparative reverse phase column chromatography (water/acetonitrile). 5- {1- [ (5-benzyl-1, 3-thiazol-2-yl) (methyl) sulfoximinyl (S-methyl) is obtained]Ethyl } -2- (trifluoromethyl) pyridine (61) as a yellowish oil (26mg, 0.061mmol, 19%) as a mixture of the racemate and the 1: 1 diastereomer.¹H-NMR(CDCl₃，400MHz)：δ＝1.89(d，J＝7.2Hz，1.5H，CHCH₃Diastereomer 1); 1.92(d, J ═ 7.2Hz, 1.5H, CHCH₃Diastereomer 2); 3.09(S, 1.5H, S-CH)₃Diastereomer 1); 3.20(S, 1.5H, S-CH)₃Diastereomer 2); 3.94(s, 1H, CH)₂Ph, diastereomer 1), 3.97(s, 1H, CH)₂Ph, diastereomer 2); 5.14(q, J ═ 7.2Hz, 0.5H, CHCH₃Diastereomer 1); 5.21(q, J)＝7.2Hz，0.5H，CHCH₃Diastereomer 2); 6.90(s, 0.5H, thiazole, diastereomer 1); 6.92(s, 0.5H, thiazole, diastereomer 2); 7.15-7.37(m, 5H, Ph); 7.71(d, J ═ 8.2Hz, 0.5H, pyridine-C₃-H, diastereomer 1), 7.72(d, J ═ 8.2Hz, 0.5H, pyridine-C₃-H, diastereomer 2); 8.09(dd,³J＝8.2Hz，⁴j-1.8 Hz, 0.5H, pyridine-C₄-H, diastereomer 1); 8.12(dd,³J＝8.2Hz，⁴j-1.7 Hz, 0.5H, pyridine-C₄-H, diastereomer 2); 8.75(d is,⁴j-1.8 Hz, 0.5H, pyridine-C₆-H, diastereomer 1); 8.79(d is a linear chain of,⁴j-1.8 Hz, 0.5H, pyridine-C₆-H, diastereomer 2);¹³C-NMR(CDCl₃，100MHz)：δ＝13.8，14.2(CHCH₃two diastereomers); 33.2.33.3 (CH)₂Ph, two diastereomers); 36.5, 36.8 (S-CH)₃Two diastereomers); 60.8, 61.6 (CHCH)₃Two diastereomers); 119.5, 119.6 (pyridine-C, two diastereomers); 125.6, 125.7(Ph, two diastereomers), 127.2, 127.3(Ph, two diastereomers, 127.5(Ph, two diastereomers), 130.1, 130.2 (pyridine-C, two diastereomers), 131.1, 131.5, (pyridine-C, two diastereomers), 132.7, 133.2 (thiazole, two diastereomers), 137.3, 137.6 (pyridine-C, 2 diastereomers), 137.9, 138.0 (thiazole, two diastereomers), 149.2, 149.4 (pyridine-C, 2 diastereomers), 165.6, 165.8 (thiazole, two diastereomers), CF₃And not detected. UPLC-MS (ESI)⁺): for C₁₉H₁₉F₃N₃OS₂Mass calculated value of (d): (M + H)⁺): 426.1, observed 426.1, UPLC-MS (ESI)^-): for C₁₉H₁₉F₃N₃OS₂Mass calculated value of (d): (M-H)⁺): 424.1, observation 424.1.

Example XIII.5- {1- [ methyl (5-phenyl-1, 3-thiazol-2-yl)) Sulfo oxime radical]Ethyl } -2- (trifluoro benzene) Preparation of methyl) pyridine (62)

(1) Preparation of 2-bromo-2-phenylacetaldehyde: dibromobarbituric acid (1.43g, 5mmol) was dissolved in diethyl ether (40mL) and phenylacetaldehyde (1.20g, 10mmol) was added. After stirring overnight at room temperature, a precipitate of barbituric acid was observed. The reaction mixture was filtered and then saturated NaHCO₃(1X 40mL) and brine (2X 40 mL). The mixture is passed over Na₂SO₄Drying, filtering and removing the solvent under reduced pressure. GC-MS analysis of the concentrate showed 2-bromo-2-phenylacetaldehyde as the sole product. (2) Preparation of (62): reacting N- (methyl (oxo) {1- [6- (trifluoromethyl) -pyridin-3-yl)]Ethyl } -lambda⁶Thio-ene) thiourea (J) (100mg, 0.321mmol) was suspended in EtOH (1mL) and a solution of 2-bromo-2-phenylacetaldehyde (64mg, 0.321mmol, 1.0 equiv.) in EtOH (0.6mL) was added. The reaction mixture was stirred at room temperature for 2h, then heated to reflux and held for 30 min. The solvent was removed under reduced pressure. UPLC-ESI/MS analysis of the crude residue showed almost quantitative formation of (62). To remove traces of starting material, the residue was purified by preparative reverse phase column chromatography (water/acetonitrile). 5- {1- [ methyl (5-phenyl-1, 3-thiazol-2-yl) sulfoximinyl radical is obtained]Ethyl } -2- (trifluoromethyl) pyridine (62) as a yellow oil (66mg, 0.161mmol, 50%) as a mixture of the racemate and the 1: 1 diastereomer.¹H-NMR(CDCl₃，400MHz)：δ＝1.92(d，J＝7.2Hz，1.5H，CHCH₃Diastereomer 1); 1.96(d, J ═ 7.2Hz, 1.5H, CHCH)₃Diastereomer 2); 3.11(S, 1.5H, S-CH)₃Diastereomer 1); 3.21(S, 1.5H, S-CH)₃Diastereomer 2); 5.14(q, J ═ 7.2Hz, 0.5H, CHCH₃Diastereomer 1); 5.24(q, J ═ 7.2Hz, 0.5H, CHCH₃Diastereomer 2); 7.29-7.48(m, 5H, Ph); 7.73(d, J ═ 7.7Hz, 0.5H, pyridine-C₃-H, not pairEnantiomer 1), 7.75(d, J ═ 7.8Hz, 0.5H, pyridine-C₃-H, diastereomer 2); 8.05-8.12(m, 1H pyridine-C)₄-H, diastereomer 1, 2); 8.78(d is,⁴j-1.6 Hz, 0.5H-pyridine-C₆-H, diastereomer 1); 8.81 (d) of the total weight of the polymer,⁴j-1.6 Hz, 0.5H, pyridine-C₆-H, diastereomer 2); thiazole-H hidden in CHCl₃Below the peak.¹³C-NMR(CDCl₃，100MHz)：δ＝13.8，14.3(CHCH₃Two diastereomers); 36.3, 36.4 (S-CH)₃Two diastereomers); 60.6, 61.3 (CHCH)₃Two diastereomers); 119.4, 119.6 (pyridine-C, two diastereomers); 124.8(Ph), 126.20, 126.21(Ph, two diastereomers); 127.7, 127.8(Ph, two diastereomers); 130.9 (pyridine-C); 131.2, 131.3; (pyridine-C, two diastereomers); 133.0 (thiazole); 137.2, 137.3 (pyridine-C, 2 diastereomers); 149.2, 149.3 (pyridine-C, 2 diastereomers); 161.0 (thiazole); 165.6, 165.8 (thiazole, two diastereomers); CF (compact flash)₃And not detected. UPLC-MS (ESI)⁺): for C₁₈H₁₇F₃N₃OS₂Mass calculation value of (M + H)⁺): 412.1, observed 411.8, UPLC-MS (ESI)^-): for C₁₈H₁₇F₃N₃OS₂Mass calculated value of (M-H)⁺): 410.1, observation 410.1.

Example XIV.5- {1- [ methyl (5-methyl-1, 3-thiazol-2-yl) sulfoximinyl group]Ethyl } -2- (trifluoro benzene) Methyl pyridine (63)

(1) Preparation of 2-bromo-propionaldehyde: dibromobarbituric acid (1.43g, 5mmol) was dissolved in diethyl ether (40mL), followed by the addition of propionaldehyde (581mg, 0.72mL, 10 mmol). After stirring at room temperature for 48h, a precipitate of barbituric acid was observed. For reactionThe mixture was filtered and then saturated NaHCO₃Aqueous (1X 40mL) and brine (2X 40 mL). Through Na₂SO₄After drying, GC-MS analysis of the concentrate confirmed that 2-bromo-propionaldehyde was present in solution as the major product. (2) Preparation of (63): in a 25mL round-bottomed flask equipped with a Vigreux column (Vigreux column) connected to a Libixi condenser (Liebig condenser), N- (methyl (oxo) {1- [6- (trifluoromethyl) -pyridin-3-yl)]Ethyl } -lambda⁶-Thienylene) thiourea (J) (100mg, 0.321mmol) was suspended in EtOH (1mL) and then an excess of a solution of 2-bromo-propionaldehyde in diethyl ether (5mL, obtained in the first step) was added. The ether was completely removed by fractional distillation over 3 h. After cooling, the distillation bridge (distillation bridge) was replaced by a reflux condenser and the remaining mixture was heated to reflux and held for 30 minutes. Finally, the solvent and the remaining 2-bromo-propanal were removed under reduced pressure. UPLC-ELSD/MS analysis of the crude residue showed almost quantitative formation of (63). To remove traces of starting material, the residue was purified by preparative reverse phase column chromatography (water/acetonitrile). 5- {1- [ methyl (5-methyl-1, 3-thiazol-2-yl) sulfoximinyl radical is obtained]Ethyl } -2- (trifluoromethyl) pyridine (63) as a yellow oil (65mg, 0.186mmol, 58%) as a mixture of the racemate and the 3: 5 diastereomer.¹H-NMR(CDCl₃，400MHz)：δ＝1.88(d，J＝7.2Hz，1.12H，CHCH₃Diastereomer 1); 1.92(d, J ═ 7.2Hz, 1.88H, CHCH₃Diastereomer 2); 2.29 (d) of the total of (d,⁴j-1.2 Hz, 1.88H, thiazole-CH₃Diastereomer 2); 2.31 (d) of (a,⁴j-1.2 Hz, 1.12H, thiazole-CH₃Diastereomer 1); 3.03(S, 1.12H, S-CH)₃Diastereomer 1); 3.15(S, 1.88H, S-CH)₃Diastereomer 2); 5.13(q, J ═ 7.2Hz, 0.63H, CHCH₃Diastereomer 2); 5.24(q, J ═ 7.2Hz, 0.37H, CHCH₃Diastereomer 1); 6.83(q,⁴j ═ 1.2Hz, 0.63H, thiazole-H, diastereomer 2); 6.86(q,⁴j ═ 1.2Hz, 0.37H, thiazole-H, diastereomer 1); 7.71(d, J ═ 8.0Hz, 0.63H, pyridine-C₃-H, diastereomer 2), 7.73(d, J ═ 8.0Hz, 0.37Hpyridine-C₃-H, diastereomer 1); 8.04-8.09(m, 1H pyridine-C)₄-H, diastereomer 1, 2); 8.73(d is,⁴j-1.8 Hz, 0.63H, pyridine-C₆-H, diastereomer 2); 8.78(d is,⁴j-1.8 Hz, 0.37H, pyridine-C₆-H, diastereomer 1).¹³C-NMR(CDCl₃100 MHz): delta-12.0 (thiazole-CH)₃)；13.8，14.3(CHCH₃Two diastereomers); 36.1, 36.3 (S-CH)₃Two diastereomers); 60.4, 61.0 (CHCH)₃Two diastereomers); 119.4, 119.5 (pyridine-C, two diastereomers); 131.5 (aromatic carbon), 132.1 (aromatic carbon), 134.5 (aromatic carbon), 134.6 (aromatic carbon), 137.1, 137.3 (pyridine-C, 2 diastereomers); 149.2, 149.3 (pyridine-C, 2 diastereomers); 164.7, 165.0 (thiazole, two diastereomers); CF (compact flash)₃And not detected. UPLC-MS (ESI)⁺): for C₁₃H₁₅F₃N₃OS₂Mass calculation value of (M + H)⁺): 350.1, observed value 350.4, UPLC-MS (ESI)^-): for C₁₃H₁₅F₃N₃OS₂Mass calculated value of (M-H)⁺): 348.1, observed value 348.0.

Example XV.5- [1- (methyl {5- [ (methylthio) methyl group)]-1, 3-thiazol-2-yl } sulfoximinyl) ethanone Base of]-2- (trifluoromethyl) pyridine (64)

(1) Preparation of 2-bromo-3- (methylthio) propanal: dibromobarbituric acid (715mg, 2.5mmol) was dissolved in diethyl ether (20mL), followed by the addition of 3- (methylthio) propanal (521mg, 5.0 mmol). After stirring overnight at room temperature, a precipitate of barbituric acid was observed. The reaction mixture was filtered and then saturated NaHCO₃Aqueous (1X 20mL) and brine (2X 40 mL). The mixture is passed over Na₂SO₄DryingAnd (4) filtering. GC-MS analysis of the concentrate showed 2-bromo-3- (methylthio) propanal as the sole product. The solvent was removed under reduced pressure. The isolated 2-bromo-3- (methylthio) propanal is polymerized in 5-10 minutes; it was used immediately for the subsequent reaction. (2) Preparation of (64): reacting N- (methyl (oxo) {1- [6- (trifluoromethyl) -pyridin-3-yl)]Ethyl } -lambda⁶-Thienylene) thiourea (J) (100mg, 0.321mmol) was suspended in EtOH (1mL) and a solution of 2-bromo-3- (methylthio) propanal (ca 65mg, 0.35mmol, 1.1 equiv.) in EtOH (0.6mL) was added. The reaction mixture was heated to reflux and held for 1 h. The solvent was removed under reduced pressure and the remaining residue was purified by preparative reverse phase column chromatography (water/acetonitrile). To obtain 5- [1- (methyl {5- [ (methylthio) methyl group)]-1, 3-thiazol-2-yl } sulfoximinyl) ethyl]-2- (trifluoromethyl) pyridine (64) as a colourless oil (7mg, 0.018mmol, 5.5%) as a mixture of racemate and 1: 1 diastereoisomer.¹H-NMR(CDCl₃，400MHz)：δ＝1.90(d，J＝7.2Hz，1.5H，CHCH₃Diastereomer 1); 1.93(d, J ═ 7.2Hz, 1.5H, CHCH₃Diastereomer 2); 2.05(S, 1.5H, S-CH)₃Diastereomer 1); 2.07(S, 1.5H, S-CH)₃Diastereomer 2); 3.08(s, 1.5H, SO-CH)₃Diastereomer 1); 3.17(s, 1.5H, SO-CH)₃Diastereomer 2); 3.70, 3.72(2H, S-CH)₂)；5.08(q，J＝7.2Hz，0.5H，CHCH₃Diastereomer 1); 5.17(q, J ═ 7.2Hz, 0.5H, CHCH₃Diastereomer 2); 6.97(s, 0.5H, thiazole, diastereomer 1); 7.00(s, 0.5H, thiazole, diastereomer 2); 7.71(d, J ═ 8.2Hz, 0.5H, pyridine-C₃-H, diastereomer 1), 7.74(d, J ═ 8.2Hz, 0.5H, pyridine-C₃-H, diastereomer 2); 8.04-8.10(m, 1H, pyridine-C)₄-H, diastereomer 1, 2); 8.75(d is,⁴j-1.8 Hz, 0.5H, pyridine-C₆-H, diastereomer 1); 8.79(d is a linear chain of,⁴j-1.8 Hz, 0.5H, pyridine-C₆-H, diastereomer 2); UPLC-MS (ESI)⁺): for C₁₄H₁₇F₃N₃OS₃Mass calculation value of (M + H)⁺): 396.1 observed 396.1, UPLC-MS (ESI)^-): for C₁₄H₁₅F₃N₃OS₂Mass calculated value of (M-H)⁺): 394.0, observation 394.1.

Example XVI.7- [ (methyl (oxo) {1- [6- (trifluoromethyl) -pyridin-3-yl)]Ethyl } -lambda ⁶ Sulfur (ii) sulfide Radical) amino]-4, 5-dihydro [1, 3 ]]Thiazolo [4, 5-e ]][2，1，3]Benzoxadiazole (65)

Reacting N- (methyl (oxo) {1- [6- (trifluoromethyl) -pyridin-3-yl)]Ethyl } -lambda⁶Thio (ene) thiourea (J) (100mg, 0.321mmol) and 5-bromo-6, 7-dihydrobenzo [ c][1，2，5]Oxadiazol-4 (5H) -one (76.6mg, 0.353mmol, 1.1 equiv.) is suspended in EtOH (1.6 mL). The reaction mixture was stirred at room temperature for 2h, then heated to reflux and held for 1 h. The hot solution was filtered through a 0.45 μm nylon syringe filter and the filtrate was stored overnight at-20 ℃. Obtaining 7- [ (methyl (oxo) {1- [6- (trifluoromethyl) -pyridin-3-yl)]Ethyl } -lambda⁶Thio) ene amino]-4, 5-dihydro [1, 3 ]]Thiazolo [4, 5-e ]][2，1，3]Benzoxadiazole (65) in the form of pale yellow crystals (70mg, 0.163mmol, 51%) as a 1: 1 mixture of diastereomers (racemate), which is isolated by filtration, washed with a small amount of cold ethanol and then dried under high vacuum.¹H-NMR(DMSO-d₆，400MHz)：δ＝1.87(d，J＝6.9Hz，1.5H，CHCH₃Diastereomer 1); 1.89(d, J ═ 6.9Hz, 1.5H, CHCH₃Diastereomer 2); 3.06-3.27(m, 4H, CH)₂-CH₂Diastereoisomers 1, 2); 3.42(S, 1.5H, S-CH)₃Diastereomer 1); 3.43(S, 1.5H, S-CH)₃Diastereomer 2); 5.34(q, J ═ 6.9Hz, 1H, CHCH₃Diastereoisomers 1, 2); 7.96(d, J ═ 7.7Hz, 0.5H, pyridine-C₃-H, diastereomer 1), 7.98(d,j ═ 7.8Hz, 0.5H, pyridine-C₃-H, diastereomer 2); 8.21-8.26(m, 1H, pyridine-C)₄-H, diastereomer 1, 2); 8.85(d, 0.5H)⁴J-1.6 Hz, pyridine-C₆-H, diastereomer 1); 8.86(d, 0.5H,⁴j-1.6 Hz, pyridine-C₆-H, diastereomer 2).¹³C-NMR(DMSO-d₆，100MHz)：δ＝13.3，13.6(CHCH₃Two diastereomers); 17.9 (bimodal, CH)₂Two diastereomers); 20.4 (doublet, CH)₂Two diastereomers); 36.4, 36.5 (S-CH)₃Two diastereomers); 60.8, 60.9 (CHCH)₃Two diastereomers); 119.4, 119.5 (pyridine-C, two diastereomers); 120.3(q,²J(C-F)＝271.5Hz，CF₃two diastereomers), 131.6, 131.9; (pyridine-C, two diastereomers); 132.0, 132.1 (aromatic carbon, two diastereomers), 132.4, 132.5 (aromatic carbon, two diastereomers); 138.0, 138.1 (pyridine-C, two diastereomers); 145.0 (bimodal, Ar, two diastereomers); 145.0, 145.1 (aromatic carbon, two diastereomers); 149.9 (bimodal, pyridine-C, two diastereomers); 151.2 (bimodal, Ar, two diastereomers); 166.3, 166.6 (thiazole, two diastereomers)⁺): for C₁₆H₁₅F₃N₅O₂S₂Mass calculation value of (M + H)⁺): 430.1, observed 430.1, UPLC-MS (ESI)^-): for C₁₆H₁₃F₃N₅O₂S₂Mass calculated value of (M-H)⁺): 428.1, observed value 428.1.

Example XVII.5- {1- [ methyl (5-methyl-4-phenyl-1, 3-thiazol-2-yl) sulfoximinyl group]Second step Preparation of 2- (trifluoromethyl) pyridine (66)

In a microwave crimp tube (crimp tube), N- (methyl (oxo) {1- [6- (trifluoromethyl) -pyridin-3-yl)]Ethyl } -lambda⁶Thio-ene) thiourea (J) (200mg, 0.642mmol) was suspended in EtOH (3mL) and 2-bromo-1-phenylpropan-1-one (137mg, 87 μ L, 0.642mmol) was added via syringe with stirring. The reaction mixture was sealed and then heated to 85 ℃ and held in a microwave for 15 minutes. The solvent was subsequently removed on a rotary evaporator and the remaining residue was purified by preparative reverse phase chromatography (water/acetonitrile). Two fractions were separated, containing mixtures of diastereomers in different ratios. Fraction 1 contained 5- {1- [ methyl (5-methyl-4-phenyl-1, 3-thiazol-2-yl) sulfoximinyl]Ethyl } -2- (trifluoromethyl) pyridine (66) (45mg, 0.106mmol, 16%) as a yellowish foam (2: 1-mixtures of diastereomers 1 and 2, racemate). Fraction 2 contained (66) (88mg, 0.207mmol, 32%) as a colourless oil (1: 3-mixture of diastereomers 1 and 2 (racemate)).¹H-NMR(CDCl₃，400MHz)：δ＝1.88(d，J＝7.2Hz，0.75H，CHCH₃Diastereomer 1); 1.95(d, J ═ 7.2Hz, 2.25H, CHCH₃Diastereomer 2); 2.41(s, 2.25H, thiazole-CH)₃Diastereomer 2); 2.44(s, 0.75H, thiazole-CH)₃Diastereomer 1); 3.09(S, 0.75H, S-CH)₃Diastereomer 1); 3.24(S, 2.25H, S-CH)₃Diastereomer 2); 5.25(q, J ═ 7.2Hz, 0.75H, CHCH₃Diastereomer 2); 5.37(q, J ═ 7.2Hz, 0.25H, CHCH₃Diastereomer 1); 7.26-7.34(m, 1H, p-H, Ph, two diastereomers); 7.35-7.44(m, 2H, Ph, two diastereomers); 7.54-7.62(m, 2H, Ph, two diastereomers); 7.70(d, J ═ 8.2Hz, 0.75H, pyridine-C₃-H, diastereomer 2), 7.74(d, J ═ 8.2Hz, 0.25H, pyridine-C₃-H, diastereomer 1); 8.07(dd,³J＝8.2Hz，⁴j-2.0 Hz, 0.75H, pyridine-C₄-H, diastereomer 2), 8.10(dd,³J＝8.2Hz，⁴j-2.0 Hz, pyridine-C₄-H, 0.25H, notEnantiomer 1); 8.72(d is a linear sum of,⁴j-2.0 Hz, 0.75H, pyridine-C₆-H, diastereomer 2); 8.78(d is,⁴j-2.0 Hz, 0.25H, pyridine-C₆-H, diastereomer 1).¹³C-NMR(CDCl₃100 MHz): delta-12.28 (thiazole-CH)₃Diastereomer 2); 12.43 (thiazole-CH)₃Diastereomer 1); 13.6 (CHCH)₃Diastereomer 1); 14.4 (CHCH)₃Diastereomer 2); 36.4 (S-CH)₃Diastereomer 1); 36.6 (S-CH)₃Diastereomer 2); 60.2 (CHCH)₃Diastereomer 1); 60.9 (CHCH)₃Diastereomer 2); 119.4 (pyridine-C, diastereomer 2); 119.6 (pyridine-C, diastereomer 1); 120.5 (aromatic carbon, diastereomer 2); 121.5 (aromatic carbon, diastereomer 1); 126.0 (bimodal, Ph, two diastereomers); 127.07 (aromatic carbon, diastereomer 2); 127.13 (aromatic carbon, diastereomer 1); 127.18 (aromatic carbon, diastereomer 1); 127.28 (aromatic carbon, diastereomer 2); 131.3; (pyridine-C, diastereomer 2; no corresponding diastereomer detected); 134.0 (aromatic carbon, diastereomer 2; no corresponding diastereomer detected); 137.1 (pyridine-C, diastereomer 1); 137.3 (pyridine-C, diastereomer 2); 149.3 (pyridine-C, diastereomer 2); 149.4 (pyridine-C, diastereomer 1); 161.9 (thiazole, diastereomer 2); 162.2 (thiazole, diastereomer 1); 164.4 (thiazole, diastereomer 2, no corresponding diastereomer detected); 1 quartet aromatic carbon; CF (compact flash)₃And not detected. UPLC-MS (ESI)⁺): for C₁₉H₁₉F₃N₃OS₂Mass calculation value of (M + H)⁺): 426.1, observed 425.9, UPLC-MS (ESI)^-): for C₁₉H₁₇F₃N₃OS₂Mass calculated value of (M-H)⁺): 424.1, observed value 424.

Example XVIII.5- {1- [ (4, 5-dimethyl-1, 3-thiazol-2-yl) (methyl) sulfoximinyl group]Second step 2- (trifluoromethyl) pyridinePyridine (67)

In a microwave crimp tube, N- (methyl (oxo) {1- [6- (trifluoromethyl) -pyridin-3-yl)]Ethyl } -lambda 6-sulphenylene) thiourea (J) (200mg, 0.642mmol) was suspended in EtOH (3mL) and 3-bromobutan-2-one (151mg, 69. mu.L, 0.642mmol) was added via syringe with stirring. The reaction mixture was sealed and then heated to 85 ℃ and held in a microwave for 15 minutes. The solvent was subsequently removed on a rotary evaporator and the remaining residue was purified by preparative reverse phase chromatography (water/acetonitrile). 5- {1- [ (4, 5-dimethyl-1, 3-thiazol-2-yl) (methyl) sulfoximinyl (I) is obtained]Ethyl } -2- (trifluoromethyl) pyridine (67) as a mixture of 1: 1 diastereomers as a light yellow oil (67mg, 0.185mmol, 29%).¹H-NMR(CDCl₃，400MHz)：δ＝1.89(d，J＝7.2Hz，1.5H，CHCH₃Diastereomer 1); 1.93(d, J ═ 7.2Hz, 1.5H, CHCH₃Diastereomer 2); 2.15(s, 1.5H, thiazole-CH)₃One diastereomer); 2.17(s, 1.5H, thiazole-CH)₃One diastereomer); 2.18(s, 1.5H, thiazole-CH)₃One diastereomer); 2.20(s, 1.5H, thiazole-CH)₃One diastereomer); 3.04(S, 1.5H, S-CH)₃Diastereomer 1); 3.15(S, 1.5H, S-CH)₃Diastereomer 2); 5.11(q, J ═ 7.2Hz, 0.5H, CHCH₃Diastereomer 1); 5.22(q, J ═ 7.2Hz, 0.5H, CHCH₃Diastereomer 2); 7.71(d, J ═ 8.1Hz, 0.5H, pyridine-C₃-H, diastereomer 1), 7.73(d, J ═ 8.1Hz, 0.5H, pyridine-C₃-H, diastereomer 2); 8.08(dd,³J＝8.1Hz，⁴j-2.0 Hz, 0.5H, pyridine-C₄-H, diastereomer 1); 8.10(dd,³J＝8.1Hz，⁴j-2.0 Hz, 0.5H, pyridine-C₄-H, diastereomer 2); 8.72(d is a linear sum of,⁴j-2.0 Hz, 0.5H, pyridine-C₆-H, diastereomer 1); 8.78(d is,⁴j-2.0 Hz, 0.5H, pyridine-C₆-H, diastereomer 2).¹³C-NMR(CDCl₃100 MHz): delta 10.9, 11.0 (thiazole-CH)₃Two diastereomers); 13.8, 14.4 (CHCH)₃Two diastereomers); 14.4 (bimodal, thiazole-CH)₃Two diastereomers); 36.3, 36.5 (S-CH)₃Two diastereomers); 60.5, 61.2 (CHCH)₃Two diastereomers); 117.9, 118.0 (aromatic carbon, two diastereomers); 119.4, 119.5 (pyridine-C, two diastereomers); 131.4, 132.1 (aromatic carbon, two diastereomers), 137.1, 137.4 (pyridine-C, 2 diastereomers); 141.7, 141.9 (aromatic carbon, two diastereomers) 149.3, 149.4 (pyridine-C, 2 diastereomers); 161.4, 161.7 (thiazole, two diastereomers); CF (compact flash)₃And not detected. HPLC-MS (ESI)⁺): for C₁₄H₁₇F₃N₃OS₂Mass calculation value of (M + H)⁺): 364.1, observed value 364.5, HPLC-MS (ESI)^-): for C₁₄H₁₅F₃N₃OS₂Mass calculated value of (M-H)⁺): 362.1, observation 361.8.

Example XIX.5- {1- [ [4- (4-bromophenyl) -5-methyl-1, 3-thiazol-2-yl ] methyl](methyl) sulfooximido] Ethyl } -2- (trifluoromethyl) pyridine (68)

In a microwave crimp tube, N- (methyl (oxo) {1- [6- (trifluoromethyl) -pyridin-3-yl)]Ethyl } -lambda⁶-Thienylene) thiourea (J) (200mg, 0.642mmol) was suspended in EtOH (3mL) and 2-bromo-1- (4-bromophenyl) propan-1-one (187mg, 0.642mmol) was added with stirring. The reaction mixture was sealed and then heated to 85 ℃ and held in a microwave for 15 minutes. Then rotate onThe solvent was removed on a rotary evaporator and the remaining residue was purified by preparative reverse phase chromatography (water/acetonitrile). Two fractions were separated, containing mixtures of diastereomers in different ratios. Fraction 1 contains 5- {1- [ [4- (4-bromophenyl) -5-methyl-1, 3-thiazol-2-yl group](methyl) sulfooximido]Ethyl } -2- (trifluoromethyl) pyridine (68) (43mg, 0.085mmol, 13%) as a white foam (1: 3-mixture of diastereomers 1 and 2, racemate). Fraction 2 contained (68) (77mg, 0.153mmol, 24%) as off-white crystals (2: 1-mixture of diastereomers 1 and 2 (racemate)):¹H-NMR(CDCl₃，400MHz)：δ＝1.90(d，J＝7.2Hz，2H，CHCH₃diastereomer 1); 1.95(d, J ═ 7.2Hz, 1H, CHCH₃Diastereomer 2); 2.39(s, 1H, thiazole-CH)₃Diastereomer 2); 2.42(s, 2H, thiazole-CH)₃Diastereomer 1); 3.07(S, 2H, S-CH)₃Diastereomer 1); 3.22(S, 1H, S-CH)₃Diastereomer 2); 5.14(q, J ═ 7.2Hz, 0.33H, CHCH₃Diastereomer 2); 5.25(q, J ═ 7.2Hz, 0.67H, CHCH₃Diastereomer 1); 7.42-7.54(m, 4H, Ph, two diastereomers); 7.71(d, J ═ 8.0Hz, 0.33H, pyridine-C₃-H, diastereomer 2), 7.74(d, J ═ 8.0Hz, 0.67H, pyridine-C₃-H, diastereomer 1); 8.06(dd,³J＝8.0Hz，⁴j-2.0 Hz, (1-x) H, pyridine-C₄-H, one diastereomer), 8.08(dd,³J＝8.2Hz，⁴j-2.0 Hz, x H, pyridine-C₄-H, one diastereomer); 8.72(d is a linear sum of,⁴j-2.0 Hz, 0.33H, pyridine-C₆-H, diastereomer 2); 8.78(d is,⁴j-2.0 Hz, 0.67H, pyridine-C₆-H, diastereomer 1).¹³C-NMR(CDCl₃100 MHz): delta-12.41 (thiazole-CH)₃Diastereomer 2); 12.43 (thiazole-CH)₃Diastereomer 1); 13.7 (CHCH)₃Diastereomer 1); 14.4 (CHCH)₃Diastereomer 2); 36.4 (S-CH)₃Diastereomer 1); 36.6 (S-CH)₃Is not right toEnantiomer 2); 60.5 (CHCH)₃Diastereomer 1); 61.1 (CHCH)₃Diastereomer 2); 119.4 (pyridine-C, diastereomer 2); 119.6 (pyridine-C, diastereomer 1); 120.0 (aromatic carbon, diastereomer 1); 120.9 (aromatic carbon, diastereomer 1); 121.1 (aromatic carbon, diastereomer 2); 128.7(Ph, diastereomer 1); 128.8(Ph, diastereomer 2); 130.16(Ph, diastereomer 2); 130.22(Ph, diastereomer 1); 131.3; (pyridine-C, diastereomer 2); 132.0 (pyridine-C, diastereomer 1); 133.1 (aromatic carbon, two diastereomers); 137.0 (pyridine-C, diastereomer 1); 137.2 (pyridine-C, diastereomer 2); 143.9 (aromatic carbons, two diastereomers); 149.3 (pyridine-C, diastereomer 2); 149.4 (pyridine-C, diastereomer 1); 162.0 (thiazole, diastereomer 2); 162.3 (thiazole, diastereomer 1); 1 quartet aromatic carbon; CF (compact flash)₃And not detected. UPLC-MS (ESI)⁺): for C₁₉H₁₈BrF₃N₃OS₂Mass calculation value of (M + H)⁺): 504.0, 506.0, observed 404.1, 506.1UPLC-MS (ESI)^-): for C₁₉H₁₆BrF₃N₃OS₂Mass calculated value of (M-H)⁺): 502.0, 504.0, observation 502.1, 504.1.

Example XX.5- {1- [ [5- (difluoromethyl) -1, 3, 4-thiadiazol-2-yl](methyl) sulfooximido]Second step Preparation of 2- (trifluoromethyl) pyridine (69) yl

To 5- [1- (methylsulfonoximido) ethyl]To a solution of (E) -2- (trifluoromethyl) pyridine (400mg, 1.59mmol) in acetonitrile (5mL) was added 1, 1' -thiocarbonyldiimidazole (353mg, 1.59mmol, 1 eq) and the mixture was stirred overnight. Another aliquot of 1, 1' -thiocarbonyldiimidazole (71mg, 0.317mmol, 0.2 eq) was added and the mixture was mixedThe compound was heated to 60 ℃ and held for two hours. The solvent was removed under reduced pressure and the residue was dissolved in CHCl₃Then, it was washed five times with water. Organic phase drying (Na)₂SO₄) Then, chloroform was removed under reduced pressure. Obtaining N- (methyl (oxo) {1- [6- (trifluoromethyl) -pyridin-3-yl)]Ethyl } -lambda⁶-sulfenyl) -1H-imidazole-1-thiocarboxamide (carbothioamide) (Y) as an orange-brown residue which was dried under high vacuum overnight (371mg, 1.02mmol, 64%). A1: 1 mixture of diastereomers was observed by UPLC-UV/ELSD and NMR, with a purity of 94%, which was sufficient for subsequent conversions. Higher purity was obtained by passing the residue through a plug of silica gel (7.5% MeOH in CHCl)₃Solution) to obtain.¹H NMR(CDCl₃，400MHz)：δ＝1.83(d，J＝7.1Hz，1.5H，CHCH₃Diastereomer 1); 1.86(d, J ═ 7.1Hz, 1.5H, CHCH₃Diastereomer 2); 2.86(S, 1.5H, S-CH)₃Diastereomer 1); 2.89(S, 1.5H, S-CH)₃Diastereomer 2); 4.32(q, J ═ 7.1Hz, 0.5H, CHCH₃Diastereomer 1); 4.37(q, J ═ 7.1Hz, 0.5H, CHCH₃Diastereomer 2); 7.68-7.85(m, 2H, Ar), 7.97-8.14(m, 2H, Ar), 8.67-8.82(m, 2H, Ar), UPLC-MS (ESI)⁺): for C₁₃H₁₂F₃N₄OS₂Mass calculation value of (M + H)⁺): 363.0 observed 363.1, UPLC-MS (ESI)^-): for C₁₃H₁₄F₃N₄OS₂Mass calculated value of (M-H)⁺): 361.0, observation 361.1.

Reacting N- (methyl (oxo) {1- [6- (trifluoromethyl) -pyridin-3-yl)]Ethyl } -lambda⁶-sulfenyl) -1H-imidazole-1-thiocarboxamide (Y) (300mg, 0.83mmol) was dissolved in acetonitrile (10mL) and then cooled to 0 ℃. While stirring, hydrazine (64-65% aqueous solution, 30.8. mu.L) was added via syringe31.9mg, 0.64 mmol). After 10 minutes, the mixture was poured into saturated NH₄To a Cl solution (100mL), it was taken up in CHCl₃Extracted once (100 mL). Organic phase with equal portions of saturated NH₄Washed with aqueous Cl until the aqueous phase is slightly acidic, then over Na₂SO₄And (5) drying. After filtration, difluoroacetic anhydride (154 μ L, 216mg, 1.24mmol) was added dropwise to the organic phase, which was then stirred at room temperature for 20 minutes. The solvent was removed under reduced pressure. The crude concentrate contained the desired difluoroacetylaminourea (41%, unstable) and difluoroacetamide as the major product (54%). The crude concentrate was dissolved in 1, 2-dichloroethane (10mL) and POCl was added dropwise₃(2mL) with stirring. The mixture was heated to 75 ℃ in a microwave and held for 5 minutes, then slowly added 150ml of saturated NaHCO₃In aqueous solution. After decomposition of phosphoryl chloride, the mixture was taken up in CHCl₃(3X 50 mL). The combined organic phases are saturated with NH₄Aqueous OH (4X 50mL), saturated NH₄Washed with aqueous Cl (50mL aliquots until neutral) and Na₂SO₄Drying and then removing the solvent under reduced pressure 5- {1- [ [5- (difluoromethyl) -1, 3, 4-thiadiazol-2-yl](methyl) sulfooximido]Ethyl } -2- (trifluoromethyl) pyridine (69) was isolated by preparative reverse phase chromatography. Pure (69) (1: 1 mixture of diastereomers, racemate) was obtained as a colorless oil (12mg, 0.031mmol, 3.7%).¹H-NMR(CDCl₃，400MHz)：δ＝1.89(d，J＝7.2Hz，1.5H，CHCH₃Diastereomer 1); 1.97(d, J ═ 7.2Hz, 1.5H, CHCH₃Diastereomer 2); 3.18(S, 1.5H, S-CH)₃Diastereomer 1); 3.31(S, 1.5H, S-CH)₃Diastereomer 2); 5.21(q, J ═ 7.2Hz, 0.5H, CHCH₃Diastereomer 1); 5.27(q, J ═ 7.2Hz, 0.5H, CHCH₃Diastereomer 2); 6.79(t, J ═ 53.8Hz, 0.5H, CHF₂Diastereomer 1); 6.80(t, J ═ 53.8Hz, 0.5H, CHF₂Diastereomer 2); 7.74(d, J ═ 8.2Hz, 0.5H, pyridine-C₃-H, diastereomer 1), 7.78(d, J ═ 8.2Hz, 0.5H, pyridine-C₃-H, diastereomer 2); 8.04(dd,³J＝8.2Hz，⁴j-2.0 Hz, 0.5H, pyridine-C₄-H, diastereomer 1); 8.09(dd,³J＝8.2Hz，⁴j-2.0 Hz, 0.5H, pyridine-C₄-H, diastereomer 2); 8.73(d is,⁴j-2.0 Hz, 0.5H, pyridine-C₆-H, diastereomer 1); 8.82(d is a linear sum of,⁴j-2.0 Hz, 0.5H, pyridine-C₆-H, diastereomer 2).¹³C-NMR(CDCl₃，100MHz)：δ＝13.5，14.3(CHCH₃Two diastereomers); 36.4, 36.5 (S-CH)₃Two diastereomers); 60.8, 61.4 (CHCH)₃Two diastereomers); 109.5(t,²J＝236.2Hz，CHF₂) (ii) a 119.6, 119.8 (pyridine-C, two diastereomers); 130.3 (pyridine-C); 131.1 (pyridine-C), 137.2, 137.3 (pyridine-C, 2 diastereomers); 148.2(dd,³J＝20.1Hz，²J＝35.2Hz，CCF₂H) (ii) a 149.2, 149.4 (pyridine-C, 2 diastereomers); 169.4, 169.5 (thiadiazole-2' C); CF (compact flash)³And not detected. UPLC-MS (ESI)⁺): for C₁₂H₁₂F₅N₄OS₂Mass calculation value of (M + H)⁺): 387.0, observed 387.1, UPLC-MS (ESI)^-): for C₁₂H₁₀F₅N₄OS₂Mass calculated value of (M-H)⁺): 385.0, observed value 385.1.

Example XXI.5- {1- [ methyl (4-ethyl-1, 3-oxazol-2-yl) sulfoximinyl]Ethyl } -2- (trifluoro benzene) Preparation of methyl) pyridine (70)

To a solution of sulfoximine (H) (200mg, 0.7mmol) in 1-hydroxy-2-butanone (0.6mL, 7mmol) was added concentrated HCl (3 drops). It was allowed to stir overnight, then the reaction mixture was extracted with 1M NaOH until neutral. Extracting with ethyl acetate, drying over sodium sulfate, concentrating, and then invertingChromatographic purification to obtain 5- {1- [ methyl (4-ethyl-1, 3-oxazole-2-yl) sulfo oxime]Ethyl } -2- (trifluoromethyl) pyridine (70) as a brown oil 75mg (30%). 1: 1 mixture of two diastereomers¹H NMR(400MHz，CDCl₃) δ 8.81(s, 1H), 8.78(s, 1H), 8.15(dd, 1H), 8.11(dd, 1H), 7.77(dd, 2H), 7.02(s, 1H), 6.98(s, 1H), 5.15(q, 1H), 5.04(q, 1H), 3.22(s, 3H), 3.13(s, 3H), 2.46(m, 4H), 1.97(m, 6H), 1.21(m, 6H); LC-MS (ESI): for C₁₄H₁₅F₃N₃O₂Calculated value of S [ M-H]⁺346, observed value 346.

TABLE 6 Compounds

H-route used in example XXI.

Example XXII:2- [2- (6-Chloropyridin-3-yl) -1-oxo-tetrahydro-1H-1. lambda ⁴ -thiophen-1-ylidene]-4- Preparation of tert-butyl-1, 3-thiazole (76)

2- (6-Chloropyridin-3-yl) -1-oxo-tetrahydro-1H-1 lambda⁴-Thien-1-ylidenecyanamide (Z)) Prepared as described in patent WO2007149134 (example VI). 2- (6-Chloropyridin-3-yl) -1-oxo-tetrahydro-1H-1 lambda⁴-thiophene-1-imine-1-oxide (AA) was synthesized from (Z) according to the procedure described in example VIII. Isolated as a brown solid.¹H NMR(400MHz，CDCl₃) δ (mixture of diastereomers) 8.39(dd, 2H), 7.68-7.77(m, 2H), 7.40(m, 2H), 4.26-4.32(m, 1H), 4.10-4.17(m, 1H), 3.24-3.48(m, 4H), 2.24-2.60(m, 8H); LC-MS (ESI): observed value [ M + H]⁺231. For C₉H₁₂ClN₂The calculated value of OS is 231.

Compound (BB) was synthesized from compound (AA) according to the procedure described in example VIII. Isolated as an off-white solid.¹H NMR(400MHz，CDCl₃) δ (mixture of diastereomers) 8.47(dd, 2H), 8.21(s, 1H), 8.07-8.12(m, 2H), 7.84(dd, 1H), 7.78(d, 4H), 7.58(d, 4H), 7.30-7.45(m, 8H), 4.91-4.97(m, 1H), 4.54-4.65(m, 1H), 4.43-4.50(m, 5H), 4.25(m, 3H), 3.49-3.72(m, 2H), 2.23-2.71(m, 8H); LC-MS (ESI): observed value [ M]⁺512. For C₂₅H₂₂ClN₃O₃S₂The calculated value of (a) is 512.

Thiourea (CC) was synthesized from (BB) according to the procedure described in example VIII. Isolated as an off-white solid.¹H NMR(400MHz，DMSO-d₆) δ (mixture of diastereomers) 8.94(d, 1H), 8.88(d, 1H), 8.48(d, 1H), 8.41(dd, 2H), 8.31(d, 1H), 8.13(br d, 4H), 5.56-5.62(m, 1H), 5.00-5.11(m, 1H), 4.67-4.75(m, 1H), 3.91-4.26(m, 3H), 2.65-3.16(m, 8H); LC-MS(ESI): observed value [ M + H]⁺290. For C₁₀H₁₃ClN₃OS₂290.

2- [2- (6-Chloropyridin-3-yl) -1-oxo-tetrahydro-1H-1. lambda⁴-thiophen-1-ylidene]-4-tert-butyl-1, 3-thiazole (76) was synthesized from (CC) according to the procedure described in example VIII. Isolated as an off-white solid. Mp is 77-81 deg.C;¹H NMR(400MHz，CDCl₃) δ (mixture of diastereomers) 8.70(dd, 1H), 8.48(d, 1H), 8.40(d, 1H), 7.93(dd, 1H), 7.38(d, 2H), 6.25(s, 1H), 6.09(s, 1H), 5.44-5.51(m, 1H), 4.62-4.70(m, 1H), 4.18(m, 2H), 3.51-3.73(m, 2H), 2.36-3.12(m, 8H), 1.44(s, 9H), 1.42(s, 9H); LC-MS (ESI): observed value [ M + H]⁺370. For C₁₆H₂₁ClN₃OS₂370.

I-route used in example XXII

Example XXIII.Insecticidal test

The compounds identified in the above examples were tested against cotton aphid (cotton aphid) using the method described below.

Insecticidal test against cotton aphid (Aphis gossypii) in a leaf spray assay

Pumpkin seedlings with well-extended cotyledons were trimmed to one cotyledon per plant, then infested with cotton aphids (wingless adults and nymphs) for 1 day, followed by chemical application. Each plant was checked before chemical application to ensure uniform infestation (about 30-70 aphids per plant). Compound (2mg) was dissolved in 2ml of acetone/methanol (1: 1) solvent to form a 1000ppm stock solution. Stock solution was treated with 0.025% Tween 20/H₂O was diluted 5-fold, thereby obtaining a 200ppm solution. A hand held Devilbiss aspirating sprayer (hand-held Devilbiss inhaler type sprayer) was used to apply the spray solution to both sides of the pumpkin cotyledons until run off occurred. Four plants (in quadruplicate) were used for each compound. The control plants (solvent control) were sprayed with diluent only. The treated plants were kept in a greenhouse at about 23 ℃ and 40% RH for 3 days, and then the number of live aphids per plant was recorded. The pesticidal activity was measured from the corrected control percentage (%) by using the Abbott correction formula and is shown in "table 1-activity":

corrected percent (%) control of 100X (X-Y)/X

Wherein X ═ number of live aphids on solvent control plants

Number of live aphids on treated plants

The results are shown in Table 7.

Insecticidal test against green peach aphid (Myzus persicae) in a leaf spray assay Test (experiment)

Cabbage seedlings (with 2-3 small (3-5cm) true leaves (true leaf)) grown in 3-inch pots (pots) were used as test substrates. The seedlings were infested with 20-50 myzus persicae (wingless adults and nymphs) for 1 day, and then chemically applied. Four seedlings were used for each treatment. Compound (2mg) was dissolved in 2ml of acetone/methanol (1: 1) solvent to form a 1000ppm stock solution. Stock solution was treated with 0.025% Tween 20/H₂Diluting with O by 5 times to obtainA200 ppm solution was obtained. The solution was sprayed onto both sides of cabbage leaves using a hand-held Devilbiss air-breathing type sprayer until runoff (runoff) was formed. Control plants (solvent control) were sprayed with diluent only. The treated plants were kept in a holding room at about 23 ℃ and 40% RH for three days and then rated. Evaluation was performed by counting the number of live aphids on each plant under a microscope. Insecticidal activity was measured by using Abbott's correction formula:

corrected percent (%) control of 100X (X-Y)/X

Wherein X ═ number of live aphids on solvent control plants

Y is the number of live aphids on the treated plants.

TABLE 7 Activity

	Rating against cotton aphid on pumpkin (leaf spray)	Rating against green peach aphid on cabbage (leaf spray)
			Compound (I)	200ppm	200ppm
1	A	A

	Rating against cotton aphid on pumpkin (leaf spray)	Rating against green peach aphid on cabbage (leaf spray)
			2	A	A
3	C	A
			4	A	B
5	B	C
			6	A	A
7	A	A
			8	B	B
9	C	A
			10	C	B
11	C	B
			12	B	C
13	A	B
			14	C	B
15	C	A
			16	C	A
17	C	B
			18	C	A
19	C	A
			20	C	A
21	C	A
			22	C	A

	Rating against cotton aphid on pumpkin (leaf spray)	Rating against green peach aphid on cabbage (leaf spray)
			23	C	A
24	A	B
			25	C	B
26	C	A
			27	C	A
28	C	A
			29	C	A
30	C	A
			31	C	A
32	C	B
			33	C	A
34	C	A
			35	C	A
36	C	A
			37	C	A
38	C	A
			39	C	A
40	C	A
			41	C	A
42	C	A
			43	C	A
44	C	A

	Rating against cotton aphid on pumpkin (leaf spray)	Rating against green peach aphid on cabbage (leaf spray)
			45	C	A
46	C	A
			47	C	A
48	C	A
			49	C	A
50	C	A
			51	C	A
52	C	A
			53	C	A
54	C	B
			55	C	A
56	C	A
			57	C	B
58	C	A
			59	C	A
60	C	B
			61	C	A
62	C	A
			63	C	A
64	C	A
			65	C	A
66	C	A

	Rating against cotton aphid on pumpkin (leaf spray)	Rating against green peach aphid on cabbage (leaf spray)
			67	C	A
68	C	A
			69	C	A
70	C	A
			71	C	A
72	C	B
			73	C	A
74	C	B
			75	C	B
76	C	A
			77	C	A
78	C	B
			79	C	A

The rating scale in each case of table 7 is as follows:

percent control (or mortality)	Grade
		80-100	A
Less than 80	B
		Not tested	C

Acid and salt derivatives and solvates

The compounds disclosed herein may be in the form of pesticidally acceptable acid addition salts.

By way of non-limiting example, the amine functional group may form a salt with: hydrochloric, hydrobromic, sulfuric, phosphoric, acetic, benzoic, citric, malonic, salicylic, malic, fumaric, oxalic, succinic, tartaric, lactic, gluconic, ascorbic, maleic, aspartic, benzenesulfonic, methanesulfonic, ethanesulfonic, hydroxymethanesulfonic, and hydroxyethanesulfonic acids.

Further, by way of non-limiting example, the acid functional groups may form salts, including those derived from alkali or alkaline earth metals and those derived from ammonia and amines. Examples of preferred cations include sodium cation, potassium cation, magnesium cation, and ammonium cation.

The salt was prepared as follows: the free base form is contacted with a sufficient amount of the desired acid to provide a salt. The free base form can be recovered as follows: the salt is treated with a suitable dilute aqueous base such as dilute aqueous NaOH, dilute aqueous potassium carbonate, dilute aqueous ammonia and dilute aqueous sodium bicarbonate.

For example, in many cases, pesticides are modified to be more water soluble (more water soluble forms), for example, dimethylamine 2, 4-dichlorophenoxyacetate is a more water soluble form of the well known herbicide 2, 4-dichlorophenoxyacetic acid.

The compounds disclosed herein may also form stable complexes (complexes) with solvent molecules that remain intact after non-complexed solvent molecules are removed from the compound. These complexes are commonly referred to as "solvates".

Stereoisomers

Certain compounds disclosed herein may exist as one or more stereoisomers. The various stereoisomers include geometric isomers, diastereomers and enantiomers. Thus, the compounds disclosed herein include racemic mixtures, single stereoisomers, and optically active mixtures.

It will be appreciated by those skilled in the art that one stereoisomer may be more active than the other. The single stereoisomers and optically active mixtures can be obtained as follows: a selective synthetic method, a conventional synthetic method using a resolution of the starting material or a conventional resolution method.

Pest pests

In another embodiment, the invention disclosed in this document can be used to control pests.

In another embodiment, the invention disclosed in this document can be used to control pests of the phylum nematoda (xylumnematoda).

In another embodiment, the invention disclosed in this document can be used to control a pest of the Phylum Arthropoda (Phylum Arthropoda).

In another embodiment, the invention disclosed in this document can be used to control pests of the Subphylum chelidata (subpahylum chemera).

In another embodiment, the invention disclosed in this document can be used to control arachnid (classmarcachnida) pests.

In another embodiment, the invention disclosed in this document can be used to control pests of the Subphylum podophyllum (subpahylum Myriapoda).

In another embodiment, the invention disclosed in this document can be used to control pests of the class synephrine (classssymphyla).

In another embodiment, the invention disclosed in this document can be used to control pests of the subphyla Hexapoda (subpahylum Hexapoda).

In another embodiment, the invention disclosed in this document can be used to control insects from class insecta (classsinsta).

In another embodiment, the invention disclosed in this document can be used to control Coleoptera (Coleoptera). A non-exhaustive list of such pests includes, but is not limited to, the species Vibrio sp (Acanthoscelides spp.) (weevil), Phaseolus vulgaris (Acanthoscelides spec.) (common bean weevil), Ceratoxylum gracile (Agrilus planipenis) (emerald asper), Straus sp (Agrostis sporus spp.) (wireworm), Anoplophora glabripennis (Anopyraglibri pendula (Asian Longhorned beetle)), Anopyracea sp (Anthromonas sp.), Ananadis (Anthromonas grandis) (Apocynus weevil), Anopneumothus glopennis (Aphidius spp.) (Aphidius), Coccinum sp., Periploca species (Spirochaeta.) (Periplus nigra), Cochlothria nigra species (Marasmius), Cochlothrix sp. (Athyriopsis nigra sp.) (Athyrea), Cochlothrix (Periplaneta indica (Athyriopsis), Cochlothria purpurea chinensis (Athyriopsis), Neurospora Pea weevil (Bruchus pisorum) (pea weevil), Cacoesia spp, Callosobruchus maculatus (Callosobruchus masculinus) (southern cowpea weevil), yellow spot dew beetle (carpopophilius hemsleyanus) (dried fruit beetle), beet tortoise shell (Cassida viteta), longicorn beetle (Cereus spp), yellow spot beetle (Cereus wenshu) spop, yellow spot beetle (chrysomeid), yellow spot trifolium trifoliate (Ceromorpha), yellow spot (cabbage beetle) triocta (bean leaf beetle), yellow spot (Ceratopterus flavus), yellow spot (cabbage beetle), red beetle (cabbage beetle), yellow beetle (cabbage beetle) sporum (coriaria), yellow rice beetle (cabbage beetle) sporus (cabbage beetle), yellow beetle (cabbage beetle) sporum (cabbage beetle), yellow beetle (cabbage beetle) rice beetle (cabbage beetle, red beetle (cabbage beetle), yellow beetle (cabbage beetle) rice beetle (cabbage beetle, yellow beetle (cabbage beetle) and yellow beetle (yellow beetle) are also included in the family rice beetle, yellow beetle variety (yellow beetle, yellow beetle (yellow rice beetle, rice beetle (yellow rice beetle, rice beetle, Beetles (Cryptolepis pusillus) (flat grain beetles), Orthosiphon (Cryptolepis turcicus) or (Cryptolepis turcicus) (Turkish grain beetles), Ctenocerasus (nematode), weevil (Curculio spp) (weevil), Rhizopus (Cycleophthalamus) or (grub), Meloidogyne (Cylindroceus) or (Cylindroceus spades) (sunflowers stefly), Rhizopus (Deporus) or (Bacillus grandis) (horseweed), bark beetles (Degrees bugs) (Hildene), Melothria (beetle) or (beetle), Meloidea (beetle) or (beetles) or (beetles), Bark beetle species (ipspp.) (engraver), tobacco beetle (Lasioderma sericorne) (cigarette beetle), potato beetle (leptotrichu decemlineata) (Colorado patato beetle), liogyns fuscus, liogyssularis, rice weevil (Lissorhoptrus oryzae) flower beetle (rice water weevil), bark beetle species (lichen beetle), wood beetle (rice water beetle), maize beetle (meotlannis), bark beetle (theft beetle), rape flower beetle (Meliges americana), yellow beetle (yellow beetle), black beetle (yellow beetle), yellow beetle (yellow beetle), black beetle (yellow beetle), yellow beetle (yellow beetle) shell (yellow beetle), yellow beetle (yellow beetle, the plant species of the rose Brachypodium species (Pantomerus sp.) (elephant), the leaf-eating Brachyrhizia species (Phylophaga spp.) (May/June beetle), the Phylophaga cuyana, the yellow striped beetle species (Phylophora spp.) (Chrysomyiama punctata), the apple tiger elephant species (Phynchymes spp.), the Japanese striped beetle (Popilia japonica) (Japanese beetle), the large grain beetle (Grating beetle), the bark beetle (Rhizophora dominica) (lein beetle), the root bark beetle species (Rhizophyllum beetle.) (Euzophyllum husk), the leaf beetle (bark beetle), the root bark beetle variety (bark beetle), the leaf beetle (bark beetle) and the leaf beetle (bark beetle), the root bark beetle species (leaf) (yellow rice beetle) of the root bark beetle variety (yellow rice husk beetle) of the genus, the leaf beetle species (yellow beetle variety (yellow beetle) of the genus, the leaf beetle variety (yellow rice husk beetle variety (yellow beetle), the leaf) (yellow beetle variety (yellow rice husk), the leaf) (yellow beetle variety (yellow rice husk), the leaf) (yellow rice husk variety of the root bark beetle variety of the yellow rice husk variety (yellow rice husk variety of the root bark beetle variety (yellow rice husk), the yellow rice husk variety of the yellow rice husk variety (yellow rice husk variety of the, Tribolium castaneum (red flow beer), Tribolium confluense (confluented flow beer), bark beetle (Trogoptermavariabilie) (greenhouse beer) and Zabrus teneboiides.

In another embodiment, the invention disclosed in this document can be used to control Dermaptera (earwig).

In another embodiment, the invention disclosed in this document can be used to control vein-winged (Dictyoptera) (cockroaches). A non-exhaustive list of these pests includes, but is not limited to, German cockroach (blatta germanica) (German cockroach), oriental cockroach (blatta orientalis) (original cockroach), pennsylvania (parachloroniana), American cockroach (American cockroach), Australian cockroach (Periplaneta australiana) (austriac cockroach), brown cockroach (Periplaneta brunetta) (brown cockroach), smoky cockroach (Periplaneta fuliginosa) (cockroach), sugarcane green (sugarcane greenswamp) (surf cockroach), and long cockroach (Periplaneta rubra) (German cockroach).

In another embodiment, the invention disclosed in this document can be used to control Diptera (Diptera). A non-exhaustive list of such pests includes, but is not limited to, Aedes species (Aedespp.), lucerne fly (Agromya frontella), Adenophora species (Agromya spp.), Leaf minute fly (leaf fly), Engracilis species (Anastrephe spp.), Drosophila melanogaster (fruit fly), Caribean fly (Anastrephe spp.), Anseria Bactrocera subsp (fruit fly), Bactrocera species (Bactrocera spp.), Bactrocera melon fly (Bactrocera curvata) (meal fly), Bactrocera dorsalis (Orientia fasciata) (Oriental fly, Spirosoma platyphylla (mosquito), Bactrocera fly (fruit fly), Haemophilus flavus (fruit fly), Haemateria (horse fly), Haemateria fly (horse fly), Haemateris fly (horse fly), Haematerina fly (horse fly), Haemateris fly (horse fly), Haematerina) species (horse fly), Haemateris (horse fly), Haematerina (horse fly), Haematerina) and Haematerina) species (horse fly), Haematerina, Leaf gall mosquito species (Dasineura spp.) (gallomidge), leaf gall midge (Dasineura brassiccus) (capture ga midge), subterranean fly species (Delia spp.), gray fly (Delia platura) (seed corn plot), Drosophila species (Drosophila pp.) (vinegar fly), latrine fly species (Fannia spp.) (housefly (fly), yellow belly fly (wheat belly fly) (little fly), gray belly fly (wheat belly fly) (ladder fly), stomach fly (stomach fly) (fly nest fly), Gracillia leaf, blood disturbance (Hakkia) (fly), black fly (cabbage fly) (seedling fly), black fly (cabbage fly) (seedling fly (fly), black fly (fly, cabbage fly (fly), black fly (cabbage fly) (seedling fly), black fly (cabbage fly (leaf fly), black fly (leaf fly ), black fly (black fly, leaf fly, Fall flies (Musca australis) (face fly), house flies (Musca domestica) (house fly), sheep flies (oestrumus ovis) (sheet bot fly), european straw flies (Oscinella front) (front fly), beet spring flies (pegomaceae) (beeet ieafminers), pluriobium spp.

In another embodiment, the invention disclosed in this document can be used to control Hemiptera (Hemiptera) (true bug). A non-exhaustive list of such pests includes, but is not limited to, Lygus lucorum (Acrosternum hierare) (green stink bug), Orthosiphon aristatus (Blissus leucopterus) (chinchbug), Buctopus laevis (Calocis norvegicus) (potatoto mirid), Cimexhemithus tropicalis (Tripterical bed bug), Cimex lectus (bed bug), Dagbertussa fasciatus, Dichelops furcatus, Trigonella gossypii (Dysdercus sutus), Edessa meditataristatus, Euonymus platanus (Eurygeus) masura (Centrona), Euschistus schistus, Euschistus (eustis), Euschistus (Lepidorum), Lepidorum purpurum (Lepidorum), Lepidorum (Lepidorum, Lepidium, Le, Neuroolpus longirostris, rice green bug (Nezara virula) (southern greenstink bug), lygus planterum (phytooris spp.) (plant bug), phytooris californica, phytooris relativus, Piezodorus guilidinggi, Tetramustarus (Poecilocussuseus) (fourrounded bug), Psallius vaccinicola, Pseudacysta plateae, Scaptocoris tanea and Convolvulus species (Triatospora spp.) (blodsulfing connosu/kissing bug).

In another embodiment, the invention disclosed in this document can be used to control Homoptera (Homoptera) (aphid, scale), whitefly, leafhopper (leafhopper). A non-exhaustive list of these pests includes, but is not limited to, the species Piperi pisum (Acrythosiphin pisum) (pea aphid), the species Globium globosum (Adelges spp.) (adelgid), Beeurodera brassicae (Aleurodesis proteella) (cab whitly), the species Trialeurodes spirochaeta (Aleurodermidis), the species Trialeuroptera filiformis (Aleurothrix florosus) (woodwhitlyfly), the species Trialeurocanis albonum (Aluaspis spp.) (Amrasca biguella biguensis, the species Laodermata (Aphrphora spp.) (leafhopper), the species Triphyta rubrum (Amidophysa ranii) (California red), the species Aphis viridis (Aphyla), the species Aphis gossypiella (Aphyllum), the species Aphyllum septoria (Bectonia solani), the species Aphyllum solani (Bectonia solani), the species Aphyllum purpurea (Bectonia solani), the species Aphyllum, Bectonia solani (Bectonia solani), the species Aphyllum purpurea (Bectonia solani), the species Aphyllum (Bectonia solani), the species Aphyllum, Bectonia solani), the species Aphyllum (Bectonia solani), the species Aphyllum, Bectonia solani (Bectonia solani), the species Aphyllum, Bectonia solani), the species Apphalaea (Bectonia solani), the species Aphyll, Cabbage aphid (Brevibacterium brassicae) (cabbage aphid), Cericerus sp (Ceroplases spp.), red ceroplas (Cericerus rubens) (red wax scale), Ceonospora sp (Chionaspis spp.), Lecanis sp (Lecanis viridula), Lecanis sp (Lecanis viridans), Lecanis sp (Lecanis viridans), Lecanis viridans (Lecanis viridans), Lecanis viridans (Lecanis viridae), Lecanis viridae (Lecanis viridis viridae) (Lecanis spp), Lecanis (Lecanis spp), Lecanis viridis (Lecanis spp) (Lecanis (L), Lecanis (Lecanis spp) (Lecanis (L) (Lecanis spp) (Leoni (L) (Lecanis spp) (Lecanis (L) (Leoni), Le, Macrosteles quadratus (ash leaf hopper), Mahanarva frimbriata, Myzus persicae (green leaf hopper), Nephophora melanostictus (Nephotettix dirhodium), Nephophora melanostictus (leaf hopper), Nephotettcinia melanostictus (Nephophora nigricans) (green leaf hopper), Niphoteus niloticus (Nilaparata variegatus) (brown leaf hopper), Pieris furfurula (Parameria giganteus) (charles), Pieris nigra (paraphyllum), Pieris nigra (maize leaf hopper), Phosphaericoides (maize leaf hopper), Phosphaericus nigra (leaf hopper) (maize leaf hopper), Phosphaericoides (leaf hopper) Maize aphids (Rhapalacium maida) (corn leaf aphid), cereal ductus (Rhapalacium padi) (oat bird-cherry aphid), Lecanicillium species (Saissetiaspp), Terminalia lechleri (Saissetiae oleae) (black scale), Schizophilus graminum (Schizaphilum gramminum) (greenbug), Physalis graminis (Sitobion avenae) (English grain aphid), Sogatella furcifera (Sogatella furcifera) (white-backed planthopper), Phytophthora species (Thereoaphis) (aphid), Toumeyella sp. (Lecanis), Phytopsis sp. (acoustic aphid), Trialeuroptera leaf beetle) (green leaf aphid), Trigonococcus (Trigonococcus) (green), and Trigonococcus (aphid), and Trigonococcus (green leaf beetle).

In another embodiment, the invention disclosed in this document can be used to control Hymenoptera (Hymenoptera) (ants, wasps and bees). A non-exhaustive list of such pests includes, but is not limited to, species of the genus Clerodendrum (Acrommerx spp.), Sinkiang Blastus (Athalia rosae), Melastoma species (Attasipp.) (leafcutting ant), Melastoma species (Camplotus spp.) (carpenter ant), Trichoplusia species (Diprion spp.) (sawflies), Formica species (Formica spp.) (ants), Argentina ant (Iridomymexhumis) (Argentine ant), Coptochlamys species (Monoorium spp.), Monomorium microphyllum (littlel black ant), termites (monariom pharaonis) (Pharaoh ant), neophyllus species (neodipion spp.) (sawflies), harvest termites species (podomomycex spp.) (harvesterant), hornet species (Polistes spp.) (paper wasp), fire termites species (Solenopsis spp.) (fire ant), domesticated termites (Tapoinoma sessile) (odorous beetle ant), migratory termites species (Tenomorium spp.) (paper ant), wasp spp.) (yellow wasp spp.) (wasp.) (yelljacket), and trichogramma species (Xylocopa spp.) (carpentbee).

In another embodiment, the invention disclosed in this document can be used to control Isoptera (Isoptera) (termites). A non-exhaustive list of such pests includes, but is not limited to, Coptotermes spp (Coptotermes spp.), Triplophora formosanus (Coptotermes curcevigathus), Coptotermes spp (Coptotermes francis), Coptotermes formosanus (Coptotermes formosanus), Coptotermes formosanus (Formosan termiante), Coptotermes spp (Cornittermes spp.) (Nasuttermes termes), Coptotermes spp (Cryptotermes spp.) (Triptotermes spp.), Coptotermes spp.) (Triptotermes spp.) (Heterotermes spp.) (Desertrerubrerera termes), Coptotermes spp (Heterotermes spp.) (Microptotermes spp.)), Coptotermes spp (Microtermes spp.) (Microptotermes spp.) (Microtermes spp.) (Microptotermes spp.)), Coptotermes spp (Microptotermes spp.) (Microtermes spp.)), Coptotermes spp (Microtermes spp.) (Microptotermes spp.) (Microtermes spp.)), reticulitermes batyulensis, Reticulitermes grassei, Reticulitermes flavipes (Reticulitermes flavipes) (eastern subterranean term), Reticulitermes hagenii (Reticulitermes hagenii), Reticulitermes coensis (Reticulitermes heperus) (western subterranean term), Reticulitermes santonensis (Reticulitermes santonensis), Reticulitermes sphaericus chinensis (Reticulitermes speratus), Reticulitermes nigripes (Reticulitermes tibialis), Reticulitermes virginicus (Reticulitermes virginicus), Reticulitermes species (Schedulitermes spep), and Reticulitermes species (Zootiopsis sporus speratus) (Zoousspiotryveromyces paludis) species.

In another embodiment, the invention disclosed in this document can be used to control Lepidoptera (Lepidoptera) (moths and butterflies). A non-exhaustive list of such pests includes, but is not limited to, Achoeajanata, Trichoplusia species (Adoxophyes spp.), Trichoplusia lanuginosa (Adoxophyes orana), Gekko sp (Agrostis spp.), Phlebia sp (Rhizophora cutworm), Bombyx mori (Agrostis ipsilon) (black cutword), Trichoplusia gossypii (Albama argillacea) (cotton leaf word), Amorbia cuneata, Amylosis trashitella (Navelogragrange), Anacoptidia degertaria, Trichoplusia (Anacardis linella) (peach twigs borygur borrelia), Trichoplusia (Annulata) (bud), Trichoplusia (Boscholaria), Pseudoptera (Occidenta) and Spodoptera (Boletia), Pseudoptera (Occidula (Boletia) and Gracilaria), Pseudoptera (Bodinaria) and Gracilaria (Bodinaria) and Spodopterocarpus (Bodinaria), Spinosa) and Spirochaeta (Bodinaria) species (Bodinaria), Spinacia (Bodinaria) and Bodinaria (Bodinaria) can, Capua reticulana, peach fruit moth (Carposina niponensis) (peach fruit moth), graminea species (Chilo spp.), mango lateral tail moth (Choumeta transversas) (mango shoot borre), rose leaf roller moth (Choristeuropaea) (ostrinia rosea), armyworm (ostrinia nubilalis), Spodoptera species (Choristodiella spp.), rice leaf roller (Cnaphaloceras medinalis) (grass leaf roller), butterfly species (collagen spp.), litchi grain borer (Conpomorpha crassula), aromatic wood moth (Cossus) (moth) (diaphora punctata), diaphora punctata (diaphora punctata), borer ostrinia punctata (diaphora punctata), borer (diaphora punctata), corn leaf moth (diaphora punctifera), corn leaf moth (borer (diaphora punctata), corn borer (borer punctata) (corn borer), corn borer (corn borer), corn leaf moth) (corn borer spongiosa (corn borer), corn borer (corn borer) and corn borer (corn borer), corn borer (corn borer) can (corn borer) and corn borer (corn borer) are, Diamond species (Earias spp.) (Helicoverpa armigera), Egyptia diamond (Egyptia insulata) (Egyptian bollworm), Egyptia diamond (Eariastella), Rough northern bollworm (Rough northern bollworm), Ecdytopha aurantianum, southern corn borer (Elastmopsis lignosollus) (leiser cornstem bor), Epiphysistratta strattata (light brown apple bud), Epithroma species (Ephemeraceae), Ostrinia furnacalis (Hedysia punctata), Ostrinia furalis (Hedysenta), Ostrinia furalis (Hedysentaea), Ostrinia furalis) (European moth), Ostrinia (Hedysarus armorida), Ostrinia furalis (Hedysarus punctata), Ostrinia punctata (Hedysenta), Ostersize (Hedysia punctata), Ostersize moth (Ostersize), Ostertagia punctifera webber, Ostersize (Fabricius), Osteria punctifera webea), Osterea fructica (Fabricius) and Egyptica (Fabricius) species (Fabricius), Ostrinia punctifera (Ostrinia armywia armyworm (Fabricius), Ostrinia armyworm (Fabricius), Eudragia armyworm (Fabricius) and Egyo (Grapholus plusia), Euschist, Sporina), Euschist The species of the genus Helicoverpa (Helicoverpa spp.) (Spodoptera exigua), Helicoverpa armigera (Helicoverpa armigera) (cotton bollworm), Helicoverpa zea (Helicoverpa armigera) (bollworm/corn earworm), Helicoverpa armigera (Heliotis spp.) (Spodoptera), Helicoverpa virescens (Heliotis virescens) (tobaco budworm), Helicoverpa sinensiformis (Hellula undalis) (cabbagwebworm), Indorella spp. (Roots burgers), Lycopersicon esculentus (Keifida), Helicoverpa virescens (tomato yellow corn earella) (tomato pinocephalia), Helicoverpa armigera (Helicoverpa armigera) (cabbage), Helicoverpa armigera (Helicoverpa armigera) and Spodoptera (Spodopterocarpa), Spodopterocarpa armyworm (Spodopterocarpa punctata) (looper), Spodopterocarpa punctifera (Spodopterocarpa), Spodopterocarpa punctata (Spodoptera), Spodopterocarpa indica (Spodopterocarpa) and Spodopterocarpa (Spodopterocarpa) Spodopterocarpa Pod borer (Maruca testularis) (sugared borre), bagworm (moth planna) (bagwork), Mythimna uniipuncum (trueramyworm), Neocallinodoides elegans (small tomato borre), Ostrinia nubilalis (European corn borre), Oxydia vesula, Pandemia cerana (common citrus), apple leaf moth (Indian cabbage), apple leaf moth (apple leaf moth) (cabbage leaf moth), apple leaf moth (apple leaf moth) (apple leaf moth), African leaf moth (cabbage leaf moth) (cabbage leaf moth (apple leaf moth), apple leaf moth (apple leaf moth) (cabbage leaf moth) (apple leaf moth (cabbage leaf moth), apple leaf moth (cabbage leaf moth) (apple leaf moth) (cabbage leaf moth) Cabbage moth (Plutella xylostella) (diamondback moth), Polychrosis viteana (grapefero moth), orange moth (Prays endocarpa), olive moth (Prays oleae) (olivemoth), pseudolitea spp (noctuid), pseudolitea unipunctata (armyworm), soybean looper (pseudolitea includens) (soybean looper), looper (Rachiplusia nu), tryporyza incertulas (Sciphora incertulas), moth (Sesamia spp.) (hemoglobulus), Spodoptera (Spodoptera), Spodoptera (Spodoptera Spodoptera), Spodoptera trichogramma (Spodoptera), Spodoptera frugium (Spodoptera), Spodoptera (Spodoptera) and Spodoptera (Spodoptera) for preventing rice Thermoidia gemmatalis, Chlamydia armyworms (Teneola bisseliella) (webbings move), Trichoplusia ni (cab looper), Nematomyza sativae (Tuta absoluta), Nematoda species (Yponomeuta spp.), Periploca coffea pini (Red branch borer) and Periploca pipa (Zeuzera pyrina) (leopard move).

In another embodiment, the invention disclosed in this document can be used to control Mallophaga (curlicue). A non-exhaustive list of such pests includes, but is not limited to, and sheep lice (sheep biting louse), turkey cubeba (chicken body louse) and chicken feather lice (chicken feather louse).

In another embodiment, the invention disclosed in this document can be used to control Orthoptera (Orthoptera) (grasshoppers, locusts, and crickets). A non-exhaustive list of such pests includes, but is not limited to, arana nigra (anaerobe simplex) (mormonn cricket), mole cricket (gryllotalpidate) (molectricett), Locusta migratoria (Locusta migratoria), grasshopper species (Melanoplus spp.) (grasshopper), philoxera pterospora spinosa (michropenturus retrierve) (angularged wingbud katydid), pteropophyllaspp. (kaydids), desert locust (schistospora gregaria), chia triqueta (scudius furcicola) (forktail karstic bud katyidata), and branchakus nigra (melanigrornia).

In another embodiment, the invention disclosed in this document can be used to control Phthiraptera (sucking lice). A non-exhaustive list of such pests includes, but is not limited to, Haematopinus spp (cattle and pig lice), sheep jaw lice (Linoganathus ovillus) (sheet louse), head lice (Pediculus humanus capitis) (human body louse), body lice (Pediculus humanus humanus) (human body lice), and pubic lice (Pthirus pubis) (crablouse).

In another embodiment, the invention disclosed in this document can be used to control Siphonaptera (daphnaptera). A non-exhaustive list of such pests includes, but is not limited to, Ctenocephalides canis (dog flea), Ctenocephalides felis (cat flea) and human fleas (Pulex irliteans) (human flea).

In another embodiment, the invention disclosed in this document can be used to control Thysanoptera (thrips). A non-exhaustive list of such pests includes, but is not limited to, Frankliniella fusca (Tobacco's), Frankliniella occidentalis (Western flower Thrips), Frankliniella shultzii (Frankliniella Williams), Frankliniella wilsonii (Frankliniella williamis), Frankliniella glasshouse Thrips (Helothricinus) greenthicis (Greenhouse Thrips), Riphipestris cruentatus, Cirsium species (Scothricinus spp.), Citrinium aurantium (Scothricinus spp.), Cirsium tea (Scothricinus spp.), Cirsium japonicum (Pseudosium japonicum) and Thrombinalis species.

In another embodiment, the invention disclosed in this document can be used to control thysanoptera (Thysanura) (bristletail). A non-exhaustive list of such pests includes, but is not limited to, the species chlamydomonas spp (silverfish) and the species chlamydomonas microplus spp (fireburst).

In another embodiment, the invention disclosed in this document can be used to control Acarina (Acarina) (mites (mite) and ticks (tick)). A non-exhaustive list of such pests includes, but is not limited to, Apis cerana gracilis (Acarapsis woodi) (trap of honeybes), Dermatophagoides farinae (Acarus spp.) (food mites), Dermatophagoides pteronyssinus (Acarus sreatae) (grain mite), Aceria mangifera (mangobund mite), Acrophaga spinosa (Acrophagus spp.), Acrophagus solanacearus (Acrophagoides pteronyssinus) (tomatous russiae), Acrophagus pelekasi, Acrophagus dermestoides (Acrophagus pekinensis), Acrophagus schlegeli (Acrophagus schlegeli) (apple mite), Decarminella pallidiflora (Dermatophagus pallens (Dermatophagus spp.), Dermatophagus sp., Acrophagoides pterus sp., Boophilus sp. (Barbarbus sp.), Dermatophagus sp.), Dermatophagoides pterus dermatus (Bruna purpureus (Acarus sp.), Dermatophagus sp.), Dermatophagoides (Acarus sp.), Dermatophagoides pterus sp.), Dermatophagoides (Acarus sp.), Dermatophagus sp.), Dermatophagoides pterus sp.), Dermatophagus sp. (Acarus sp.), Dermatophagoides (Acarus sp.), Derma, Tetranychus species (Eotetranychus spp.), carpinus tetranyensis (Eotetranychus carpini) (yellow spider mite), Tetranychus sp (Epitimerus spp.), Tetranychus sp (Eriophus spp.), hard tick species (Ixodespp), Tetranychus sp (Metatrox spp.), Catathyris feldianus (Notoedres cat), Tetranychus parvus species (Oligonychus spp.), Calycoides (Oligonurus comatus), Tetranychus coffeensis (Oligonurus comatus), Tetranychus parvus (Oligonus comatus) (southern mite), Tetranychus urticae (Ochronus), Tetranychus sp (Tetranychus urticae) (European red mite), Tetranychus sp (Tetranychus), Tetranychus urticae (Tetranychus urticae), Tetranychus sp) (Tetranychus urticae) (Tetranychus sp), Tetranychus urticae (Tetranychus), Tetranychus urticae) (Tetranychus sp), Tetranychus urticae (Tetranychus sp) Tetranychus spp, Tetranychus urticae (twospotted spider mite), and Varroa destructor (honeybee mite).

In another embodiment, the invention disclosed in this document can be used to control Nematoda (nematodes). A non-exhaustive list of such pests includes, but is not limited to, Aphelenchoides spp (bud and leaf & pine wood) species, Heterodera spp (Belolaimus spp.) (sting wood), Cyclotella spp (Criconema spp.), Dirofilaria immitis (dog heart worm), Ditylenchus spp (stalk and bulb) species, Heteropanacea spp (Heterodera spp.) (Cyst wood), Heterocladospora maydis (Heterodera zeyla) (corn kernel nest) species, Heteropanama spp (Hierodendronella spp.) (Roylella sp.) (Romene graft), Nematoda (Pentaphylla nematode) species, Meloidogyne spp (Meloidogyne graft), Meloidogyne spp (Meloidogyne graft, Meloidogyne incognita, Meloidogyne spp.) (Meloidogyne spp (Meloidogyne graft), Meloidogyne spp (Meloidogyne spp.) (Meloidogyne spp.) (Meloidog), Meloidogyne spp (Meloidogyne spp.) (Meloidog), Meloidog (Meloidog) species, Meloidog (Meloidog, Meloidogyne spp. (Meloidog, the species Radophora (piercing nematode) and the species Rotylenchus reniformis (kidney-shaped nematode).

In another embodiment, the invention disclosed in this document can be used to control symphytum (symphylla). A non-exhaustive list of such pests includes, but is not limited to, white pine (Scutigerella immacula).

For more detailed information see "Handbook of last Control-The Behavior, Life Histroy, and Control of Household pets" by Arnold malls, 9th Edition, copyright 2004by GIE Media Inc.

Mixture of

Some of the insecticides that can be beneficially used in combination with the invention disclosed in this document include, but are not limited to, the following:

1, 2-dichloropropane, 1, 3-dichloropropene,

Abamectin (abamectin), acephate (acephate), acequinocyl (acefenamic), acetamiprid (acetamiprid), housefly phosphorus (acetoson), acetoroll, flumethrin (acrinathrin), acrylonitrile (acrylonitril), gossypol (alanycarb), aldicarb (aldicarb), sulfoxylate (aldocarb), aldrin (aldrin), allethrin (allethrin), alodamin (allothrin), oxamidine (alloamidin), norcarb (alloxacarb), alpha-cypermethrin (alphacypermethrin), alpha-ecdysone (alpha-molysone), cyathion (amidinium), amidoflumet, methiocarb (amicarbazide), amifostine (amicarbazide), azathiophos (azophos), azaphos (azophos), azophos (azophos), azathion (azophos), azathiophos (azophos), azathion (azophos), azathiophos (azophos), azophos (azophos), indometha (azophos), azophos (azophos), indometha (azophos), azophos (azophos), and azophos (azophos,

Barium hexafluorosilicate (barnium hexafluorosilicate), fluthrite (barthrin), benclothianidin (barthirin), benclothiaz, bendiocarb (benfurocarb), benfuracarb (benfuracarb), benomyl (benomyl), benoxafos (benoxafos), bensultap (bensultap), benzoxate (benzoximate), benzyl benzoate (benzybenzobenzoate), beta-cyfluthrin (beta cyfluthrin), beta-cypermethrin (beta cypermethrin), bifenazate (bifenazate), bifenthrin (bifenthrin), binapacryl (binapacryl), pyrethrum (bioallegrophyte), allethrin (bioallethrin), bioxanthomethrin (bioxanthate), borax (bisflufenoxuron), bensulide (bisfenflurron), bensulide (biborocarb), bencarb (buticarb), butfenpropicarb (butyl bromide), buthiocarb (butyl bromide), buthoxycarb (butyl bromide), bromcarb (bromcarb), bromcarb (buthiocarb), bromcarb (buthiocarb), benomyl (buthiocarb), benomyl (buthiocarb (benomyl), benomyl (benomyl, buthiocarb (benomyl), ben,

Cadusafos, calcium arsenate, lime sulphur (calcium polysulphide), carbosulfan (carbofuran), carbosulfan (carbodichlofenphos), carboxim (carbochlorfenamate), thiophosphoryl (carbofenolate), carbaryl (carbaryl), carbosulfan (carbofuran), carbodisulfide (carbosulfan), carbon tetrachloride (carbochloranthrochloride), thiophosphoryl (thiophosphor), carbosulfan (carbosulfan), cartap (carbosulfan), carboxim (carboxim), methoprene (carboxim), chlorantraniliprole (chlorofenamide), chlorofenamide (chlorofenamide), borneomycin (chlorofenamide), chlordane (chlorofenamide), chrysin (chlorofenamide), chlorfenapyr (chlorofenapyr), kafenapyr (chlorofenapyr), chlorfenapyr (chlorofenapyr), chlorfenapyr (chlorofenapyr), chlorfenapyr (chlorofenapyr), chlorfenapyr (chlorofenapyr, Chlorpyrifos (chlorpyrifos), chlorpyrifos-methyl (chlorpyrifos methyl), chlorthion (chlorpyrifos), cycloxastream (chromafenozide), cyfluthrin I (cinerin I), cyfluthrin II (cinerin II), levo-tetramethrin (cimethrin), dichloethrocarb (cloethocarb), clofentezine (cloventezine), closantel (closantel), clothianidin (clothianidine), copper acetimidate (copperarsenite), copper arsenate (copperarsenate), copper naphthenate (copperphenazine), ketonic acid (copperolenate), (copumphos), coumarate (crotonone), crotamiton (crotonothion), crotonothion (crotonothion), cyfluthrin (cyfluthrin), cyfluthrin (cyhalothrin), cyhalothrin (cyhalothrin), cyhalothrin (cy, Cyphenothrin, cyromazine, sulfothion,

D-limonene (d-limonene), dazomet (dazomet), Dibromochloropropane (DBCP), dichloroisopropyl ether (DCIP), DDT (DDT), carbofuran (decamethrin), deltamethrin (deltamethrin), tianlephos (decaphion), tianlephos O (decaphion O), tianlephos S (decaphion S), demeton (decamethrin), demeton O (decamethrin O), demeton O-methyl (decamethrin O methyl), demeton S (decamethrin S), demeton S-methyl (decamethrin S methyl), demeton S-methyl sulfide (decathion), thion (dioxathion), dithiodiazine (dithiodiazine), dithion (dimethyldithion), dithion (dimethylthion), dithion (dimethylthion), dithion (dimethyldithion (dimethylthion, Chlorothalofos (dicrotophos), dicyclanil (dicyclanil), dieldrin (dieldrin), dichlorflufen (dineochlor), diflovidazin (diflubenzuron), diflorfluthrin (dimefluthrin), methoflurophos (dimefox), dimethoate (dimercaptan), dimethoate (dimethoate), permethrin (dimethrin), methoprene (dimethybrid), dinotefuran (dineobutton), dinocap (dinocop), dinocap 4 (dinocop 4), dinocap 6 (dinocop 6), dinocap (dinocoton), nitropentyl (dinopentonton), nitroprusol (dinopopp), pentofen (dineothion), octyl (dinetofen), dinocap (dinotefuran), dinotefuran (dinone), dinotefuran (dinoflagon), dinotefuran (dinone (dinotefuran), dinotefuran (dinone (dinotefuran), dinotefuran, dinone (dinone, dinotefuran, dinone, dinotefuran, dinone, dinotefuran, dinone, dinotefuran, dinone, dinotefuran,

ecdysterone (ecdysterone), emamectin benzoate (emamectin), spinosad (EMPC), empenthrin (empenthrin), endosulfan (endosulfan), thiophosphorum (endothion), endrin (endrin), thiophen (EPN), fenaminosulf (eponenane), eprinomectin (epimeridin), esfenvalerate (esfenvalerate), epaphos, bendiocarb (ethiofencarb), ethion (ethion), ethiprole (ethiprole), pomelo (ethofenprox), ethoprophos (ethoprop), ethopropyl (ethodddd), ethyl formate (ethopropiol formate), 1, 2-dibromoethane (ethyene dibromide), 1, 2-dichloroethane (ethyene), ethylene oxide (ethofenproxide), ethofenprox (ethofenprox), ethofenprox (ethyol), ethiofenprox (ethyol), ethion (ethoprophos), ethion (ethoprofen), ethiofenproxide (ethoprofen), ethiofenprox (ethoprofen), ethiprole (ethiofenproxide), ethiprole (ethion), ethiprolide (,

Amisulfos (famshur), fenamiphos (fenamiphos), fentrazole (fenazaflor), fenazaquin (fenazaquin), fenbutatin oxide (fenbutatin oxide), pyraflufen (fenchlophos), fenocarb (fennethacarb), fenfluthrin (fenfluthrin), fenitrothion (fentrothion), fenbutacarb (fenobucarb), fenothiocarb (fenothiocarbarb), fenoxacrem (fenoxacarb), fenoxacrim (fenoxycarb), fenoxycarb (fenoxycarb), fenpropathrin (fenpropathrin), fenpyrazothrin (fenpropathrin), fenpropathrin (fenflurazote), fenflurazote (fenflurazote), fenflurazon (fenflurazon), fenflurazote (fenflurazote), fenflurazote (fenflurazone), fenflurazote (fenflurazote), fenflurazote (fenflurazon), fenflurazon (fenflurazon), fenflurazon-methyl flufen), fenflurazon (fenflurazon, fenflurazon (fenflurazon-methyl flufen), fenflurazon (fenflurazon ), fenflurazon (fenflurazon ), fenflurazon (fenflurazon, flubencide, fluvalinate, temephos (fonofos), varroate (formamidate), bensulide (formimidate), formoterol (formothion), carboxim (formpyranate), fenthion (fosmethialan), chlorpyrifos-methyl (fossililate), fosthiazate (foshiazate), vamuramidate (fosthietan), furathiocarb (furathiocarb), furfluthrin (furathirin), furfural (furfurfurfurfurfuel),

Gamma-cyhalothrin (gamma Cyhalothrin), gamma-hexachloro-hexa (gamma HCH), haloethrin (halfenprox), halofenozide (halofenozide), hexachloro-hexa (HCH), Dieldrin (HEOD), heptachlor (heptachlor), heptenophos (heptanophos), flufenthion (heliophos), hexaflumuron (hexaflumuron), hexythiazox (hexythiazox), aldrin (HHDN), hydramethylnon (hydramethylnon), hydrogen cyanide (hydroquinone), pentaerythrine (hydroprene), quinolinecarb (quinacrb), quinacr (hydrargyrib),

Neonicotinoids (imicyafos), imidacloprid (imidacloprid), imidacloprid (imiprochlorrin), indoxacarb (indoxacarb), methyl iodide (iodomethane), profenofos (IPSP), isamidofos, isazofos (isazofos), carbochlorazol (isobenzan), isocarbophos (isocarbophos), isoaldrin (isodifrin), fosfamid (isofenphos), isoprocarb (isoprocarb), isoprothiolane (isoprothiolane), triazophos (isothionate), oxazofos (isoxathion), abamectin (ivermectin), abamectin (isoprothionin),

Jasminum sambac I (jasmolin I), jasminum II (jasmolin II), iodophors (jodfenphos), juvenile hormone I (juvenile hormon I), juvenile hormone II (juvenile hormon II), juvenile hormone III (juvenile hormon III),

Kelevan, meng qi (kineprene),

Lambda-cyhalothrin (lambda cyhalothrin), lead arsenate (lead arsenate), lepimectin, bromophenol (leprophos), lindane (lindane), pyrifos (liimfos), fluoropropoxy urea (lufenuron), fosthiazate (lythidathion),

Malathion (malathion), benomyl dinitrile (malonoben), triazophos (mazidox), triazophos (mecarbam), methidathion (mecarbun), methoxazone (menazon), dithianon (mephoslan), mercurous chloride (mercurous chloride), mechlorethamine (mesulfen), methidathion (mesulfenfos), metaflumizone (metaflumizone), metam (metam), chlorfenvinphos (methamidophos), methidathion (methidathion), methiocarb (methiocarb), methamidophos (methacronophos), methoprene (methoprene), methyl chloride (methoprene), methoprene (methoprene), methyl chloride (methoprene), methoprene (methoprene), methoprene (methoprene, methoprene, Mirex (mirex), MNAF (MNAF), monocrotophos (monocrotophos), Morpothion (morphosis), moxidectin (moxidectin),

Naphthylene phosphate (naftalofos), naled, naphthalene (naphthalene), nicotine (nicotinine), norfluridide (niflumide), delphamycin (nikkomyn), nitenpyram (nitenpyram), nithiazine (nithiazine), nitrilocarb (nitrilacarb), novaluron (novaluron), noviflumuron (noviflumuron),

Omethoate, oxamyl, oxydemethyl, oxydemeton methyl, oxydeprofos, oxydisulfoton, dimethoate, dimethoa,

P-dichlorobenzene (paradiclorobenzene), parathion (parathion), methyl parathion (parathion methyl), fluazuron (pentafluron), pentachlorophenol (pentachlorophenol), permethrin, fenthion (phenokapton), phenothrin (phenothrin), phenthoate (phenoxate), phorate (phorate), phosmet (phos), parathion (phos), phosphamidon (phosphamidon), phosphine (phosphine), phosphocarb (phosphocarb), oxime (phos), phosmet (phosmet methyl), phosmet (pyrimethan), pirimicarb (pyriproxyfen), ethephos (pyriproxyfen), promethidium (pyriproxyfen), promethamine (pyriproxyfen), promethazine (potassium chloride), promethazine (potassium thiocyanate, promethazine), promethazine (I), promethazine (potassium thiocyanate), promethazine (potassium chloride), promethazine (promethazine I, promethazine I (promethazine I), promethazine (promethazine I, promethazine (promethazine I) and promethazine (promethazine I), profluthrin, tick-lice-carbofuran (procycarb), promecarb (propaphos), propargite (propargite), methoprene (protista), propoxur (propcur), ethiprole (prothion), prothiocfos (prothiocfos), pomade (prothioconazole), prothioconazole (prothioconazole), pyrazofos (pyrafluxol), pyrazofos (pyrafluthrin), pyrethrin (pyrethrin), pyrethrin (pyrethirin I), pyrethrin II (pyrethirin II), pyridaben (pyridaben), pyridalyl (pyridalyl), pyrifluquinazon, pyrimethanil (pyrimethanil), pyriproxyfen (pyriproxyfen), pyriproxyfen (pyriproxyf,

Quassia, quinoxalines, methylquinoxalines, quintiflienes, quatifies, quasiporines, and quasiporines,

Iodoethersalicylamide (rafoxanide), resmethrin (resmethrin), rotenone (rotenone), ryania (ryania),

Sabadilla (sabadilla), octamethiphos (schradan), selamectin (selamectin), silafluofen (silafluofen), sodium arsenite (sodium arsenite), sodium fluoride (sodium fluoride), sodium hexafluosilicate (sodium hexafluosilicate), sodium thiocyanate (sodium thiocyanite), fructus Perillae (solanide), spinetoram, spinosad, spirodiclofen (spirodiclofen), spiromesifen (spiromesifen), spirotetramat (spirotetramat), sulforon (sulfofluron), sulfenom (sulfiram), sulfluramid (sulfluramid), thiotep (sulffotep), sulfur (sulflur), sulfluryl fluoride (fluoride), ethylene propylene glycol (ethylene propylene glycol), sulfur (sulffos),

Tau-fluvalinate (tau fluvalinate), thiofencarb (tazimcarb), Trichomonas (TDE), tebufenozide (tebufenozide), tebufenpyrad (tebufenpyrad), pyrifos (tebuformfos), tebufenozide (teflubenzuron), tefluthrin (tefluthrin), temephos (temephos), TEPP (TEPP), cyfluthrin (terethrin), terbufos (terbufos), tetrachloroethane (tetrachlorethane), fenvinphos (tetrachlphos), trichlorosulfone (tetradifon), tetramethrin (tetramethrin), tetramethrin (tetramactrin), acaricidal (tetramethrin), theta-cypermethrin (theta), thiocyclrin (thifenprox), thiocyclam (thiophosphate), thiofenthifenpyrad), thiocarb (thifenpyrad), thifenthiocarb (thifenprox), thiocarb (thiocarb), thifenprox (thifenprox), thiocarb (thifenprox), thifenthiocarb (thifenprox), thifenprox (thifenprox), thifenthiocarb (thifenprox (thiocarb), thifenprox), thifenthiocarb (thifenthion (thiocarb), thifenthion (thifenpyrol), thifenthion (thifenthiocarb, Transfluthrin, trialeurin, trialeurothiazine, triasulfuron, triazophos, trichlorfon, isopsorrel phosphorus 3, chlorfenapyr, chlorophenoxy, triflumuron, trimethacarb, thioacrylate, triptorezine, trimethacarb, triazophos, triflumuron, trimethacarb, triazenoate, triazophos,

aphidicolinide (vamidothion), pyrazoline (vanilprole),

Dimethylcarbofuran (XMC), propoxur (xylcarb),

Zeta-cypermethrin (zeta cypermethrin) and zolaprofos.

In addition, any combination of the above insecticides can be used.

For economic and synergistic reasons, the invention disclosed in this document can also be used with herbicides and fungicides.

For economic and synergistic reasons, the invention disclosed in this document can be used with antibacterial agents (antimicrobial), germicides (bactericide), defoliants (defoliant), safeners (safers), synergists (synergists), algicides (algaecides), attractants (attractants), desiccants (desiccants), pheromones (pheromones), protectants (repellants), animal steepening agents (animal dip), avicides (avicides), disinfectants (disinfects), semiochemicals (semiochemicals) and molluscicides (moluscicides), which categories are not necessarily mutually exclusive.

For more information see "Complex of pesticide common Names" located before the filing date of this documenthttp://www.alanwood.net/pesticides/index.html). See also "The Pesticide Manual" 14^th Edition，edited by C D S Tomlin，copyright 2006 byBritish Crop Production Council。

Synergistic mixture (SYNERGISTIC MIXTURE)

The invention disclosed in this document can be used with other compounds (such as those mentioned under the heading "mixtures") to form synergistic mixtures in which the mode of action of each compound in the mixture is the same, similar or different.

Examples of modes of action include, but are not limited to: an acetylcholinesterase inhibitor; a sodium channel modulator; chitin biosynthesis inhibitors (chitin biosyntheses inhibitors); GABA-gated chloride channel antagonists (GABA-gated chloride channel antaconists); GABA and glutamate-gated chloride channel agonists (GABA and glutamate-gated chloride channel agonists); an acetylcholine receptor agonist; a MET I inhibitor; mg-stimulated ATPase inhibitor (Mg-stimulated ATPase inhibitor); nicotinic acetylcholine receptors; midgut membrane disruptor (midgut membrane disruptor); and oxidative phosphorylation interrupters (oxidative phosphorylation disrupters).

In addition, the following compounds are known as synergists and can be used with the invention disclosed in this document: piperonyl butoxide (piperonyl butoxide), piperonal aldehyde (piprost), piperonal ester (propyl isome), piperonyl butoxide (sesamex), sesamolin (sesamolin) and sulfoxide (sulfoxide).

Preparation

Insecticides are hardly suitable for application in their pure form. It is often desirable to add other materials so that the pesticide can be used in the desired concentration and in the appropriate form for ease of application, handling, transportation, storage and to maximize the activity of the pesticide. Thus, pesticides are formulated, for example, as baits (baits), concentrated emulsions (concentrated emulsions), dusts (powders), emulsifiable concentrates (emulsifiable concentrates), fumigants (fumigants), gels, granules, microencapsulated forms (microencapsulations), seed treatment agents (seed treatment), suspension concentrates, suspoemulsions (suspoemulsions), tablets, water-soluble liquids, water-dispersible granules or dry flowable (dry flowable), wettable powders (wettable powders) and ultra low volume solutions (ultra low volume solutions).

For further information on formulation type see "Catalogue of peptides for formulation types and International coding systems" Technical Monograph n ° 2, 5th Edition by CropLife International (2002).

The insecticide is most commonly applied in the form of an aqueous suspension or emulsion prepared from a concentrated formulation of the insecticide. Such water-soluble, water-suspendable or emulsifiable formulations are either solid (commonly known as wettable powders or water-dispersible granules) or liquid (commonly known as emulsifiable concentrates or aqueous suspensions). Wettable powders, which can be compressed to form water dispersible granules, contain an intimate mixture (insecticide mix) of insecticide, carrier and surfactant. The concentration of the insecticide is generally from about 10 wt% (weight percent) to about 90 wt%. The support is generally selected from attapulgite (attapulgite clay), montmorillonite (montmorillonite clay), diatomaceous earth (diatomous earth) or purified silicate (purified silicate). Effective surfactants (from about 0.5% to about 10% of the wettable powder) are selected from the group consisting of sulfonated lignins, concentrated naphthalene sulfonates, alkylbenzene sulfonates, alkyl sulfates, and nonionic surfactants (e.g., ethylene oxide adducts of alkylphenols).

Emulsifiable concentrates of the insecticide comprise an appropriate concentration of insecticide (e.g., about 50 to about 500 grams per liter of liquid) dissolved in a carrier which is a mixture of a water-miscible solvent or a water-immiscible organic solvent and an emulsifier. Useful organic solvents include aromatic solvents (particularly xylenes) and petroleum fractions (particularly the high boiling naphthalene portion and the olefinic portion of petroleum such as heavy aromatic naphtha). Other organic solvents such as terpene solvents (including rosin derivatives), aliphatic ketones (e.g., cyclohexanone) and complex alcohols (e.g., 2-ethoxyethanol) may also be used. Suitable emulsifiers for the emulsifiable concentrates are selected from the common anionic and nonionic surfactants.

Aqueous suspensions include suspensions of water-insoluble pesticides dispersed in an aqueous carrier at concentrations of from about 5% to about 50% by weight. The suspension was prepared as follows: the insecticide is finely ground and vigorously mixed into a carrier comprising water and surfactant. Ingredients such as inorganic salts and synthetic or natural gums may also be added to increase the density and viscosity of the aqueous carrier. It is generally most effective to simultaneously grind and mix the pesticide by preparing an aqueous mixture and homogenizing it in equipment such as a sand mill (sand mill), ball mill (ball mill) or piston-type homogenizer (piston-type homogenizer).

The insecticide may also be applied in the form of a granular composition which is particularly useful for application to soil. Particulate compositions typically contain from about 0.5 wt% to about 10 wt% of the pesticide dispersed in a carrier comprising clay (clay) or similar material. The above compositions are generally prepared as follows: the insecticide is dissolved in a suitable solvent and applied to a particulate carrier which has been pre-sized to a suitable particle size (range of about 0.5 to 3 mm). The above composition may also be prepared as follows: the carrier and compound are formed into a dough or paste which is then crushed and dried to obtain the desired particle size.

The pesticide-containing powder was prepared as follows: the powdered insecticide is thoroughly mixed with a suitable dusty agricultural carrier such as kaolin clay, ground volcanic rock, and the like. The dust may suitably contain from about 1% to about 10% insecticide. They can be used for seed dressing (seed dressing) or together with dust blowers for foliar application (leaf application).

It is also possible to apply the insecticide in the form of a solution in a suitable organic solvent (usually petroleum oil such as spray oil) widely used in agrochemicals.

The insecticide may also be applied in the form of an aerosol composition. In such compositions, the insecticide is dissolved or dispersed in a carrier which is a propellant mixture that can generate pressure. Packaging the aerosol composition in a container and dispensing the mixture from the container through an atomizing valve.

When the insecticide is mixed with the food or attractant or with the food and attractant, an insecticide bait is formed. When pests eat the bait, they also consume the insecticide. The bait may be in the form of a granule, gel, flowable powder, liquid, or solid. They are used in pest harborages.

Fumigants are pesticides with a relatively high vapour pressure and therefore may be present in gaseous form in sufficient concentration to kill pests in soil or enclosed spaces. The toxicity of fumigants is proportional to their concentration and exposure time. They are characterized by having good spreading ability and acting by penetrating into the respiratory system of pests or being absorbed through the epidermis of pests. Fumigants are applied for the control of stored product pests (stored product pest) under gasproof sheets (gas proof sheet) in airtight rooms or airtight buildings or in special chambers.

The insecticide may be microencapsulated by suspending particles or droplets of the insecticide in various types of plastic polymers. Microcapsules of various sizes, various solubilities, various wall thicknesses, and various permeabilities can be formed by varying the chemistry of the polymer or by varying factors in the process. These factors control the release rate of the active ingredient therein, which in turn affects the residual properties, the speed of action and the odor of the product.

The oil solution concentrate is prepared by dissolving the pesticide in a solvent that maintains the pesticide in solution. Oil solutions of insecticides generally provide faster knockdown and pest killing action than other formulations due to the insecticidal action of the solvent itself and the increased rate of uptake of the insecticide by the (integral) wax coating (wax). Other advantages of oil solutions include better storage stability, better crack penetration and better adhesion to greasy surfaces.

Another embodiment is an oil-in-water emulsion, wherein the emulsion comprises oily globules (oil globules) each provided with a lamellar liquid crystalline coating (lamellar liquid crystalline) and dispersed in the aqueous phase, wherein each oily globule comprises at least one agriculturally active compound and is each coated with a single layer or layers of layers comprising (1) at least one nonionic lipophilic surfactant, (2) at least one nonionic hydrophilic surfactant, and (3) at least one ionic surfactant, wherein the globules have an average particle size of less than 800 nanometers. Further information regarding this embodiment is disclosed in U.S. patent publication 20070027034 (published date 2/1/2007 and patent application No. 11/495,228). For ease of use, this embodiment is referred to as "OIWE".

For further information see "Insect Pest Management" 2^ndEdition by D.Dent, copy CAB International (2000). In addition, for more details see "Handbook of Pest Control-The Behavior, Life Histroy, and Control of Household pets" by Arnold Mallis, 9^th Edition，copyright 2004 by GIE Media Inc。

Other formulation Components

Generally, when the invention disclosed in this document is used in a formulation, the formulation may also contain other components. These components include, but are not limited to (this is a non-exhaustive and non-mutually exclusive list) wetting agents, spreading agents (spreaders), stickers, penetrants, buffers, release agents (sequestrant agents), anti-drift agents (drift reduction agents), compatibility agents (compatibility agents), anti-foaming agents, detergents, and emulsifiers. Several components are described next.

Wetting agents are substances that, when added to a liquid, increase the spreading or penetration capacity of the liquid by reducing the interfacial tension between the liquid and the surface on which the liquid is spread. Wetting agents perform two main functions in agrochemical formulations: increasing the rate of wetting of the powder in water during processing and manufacture to produce a concentrate or suspension concentrate in a soluble liquid; and reducing the wetting time of the wettable powder and improving the penetration of water into the water dispersible granules during mixing of the product with water in the spray tank. Examples of wetting agents for use in wettable powders, suspension concentrates and water dispersible granule formulations are sodium lauryl sulphate, dioctyl sodium sulfosuccinate (sodium dioctyl sulfosuccinate), alkylphenol ethoxylates and fatty alcohol ethoxylates.

Dispersants are substances that adsorb onto the surface of particles and help to maintain the dispersed state of the particles and prevent the particles from reaggregating. Dispersants are added to agrochemical formulations to aid in dispersion and suspension during manufacture and to help ensure that the particles are redispersed in water in a spray tank. They are widely used in wettable powders, suspension concentrates and water dispersible granules. Surfactants used as dispersants have the ability to adsorb strongly to the surface of the particles and provide a charged or steric barrier against reaggregation of the particles. The most commonly used surfactants are anionic surfactants, nonionic surfactants or mixtures of the two types. For wettable powder formulations, the most common dispersant is sodium lignosulfonate (sodium lignosulphonate). For suspension concentrates, polyelectrolytes such as sodium naphthalene sulfonate formaldehyde condensate are used to achieve very good adsorption and stabilization. Tristyrylphenol ethoxylate phosphate ester (tristyrylphenol ethylatephosphite ester) was also used. Nonionic surfactants, such as alkylaryl ethylene oxide condensates (alkyl aryl ethylene oxide condensates) and EO-PO block copolymers, are sometimes combined with anionic surfactants as dispersants for suspension concentrates. In recent years, new classes of very high molecular weight polymeric surfactants have been developed as dispersants. These dispersants have a very long hydrophobic "backbone" and a large number of ethylene oxide chains forming the "teeth" of a "comb" surfactant. These high molecular weight polymers can impart very good long-term stability to the suspension concentrate, since the hydrophobic backbone has multiple anchor points to the particle surface. Examples of dispersants used in agrochemical formulations are sodium lignosulfonates, sodium naphthalene sulfonate formaldehyde condensates, tristyrylphenol ethoxylate phosphate esters, fatty alcohol ethoxylates, alkyl ethoxylates, EO-PO block copolymers and graft copolymers.

Emulsifiers are substances which stabilize a suspension of droplets of one liquid phase in another. In the absence of an emulsifier, the two liquids would separate into two immiscible liquid phases. The most commonly used emulsifier blends contain an alkylphenol or fatty alcohol having 12 or more ethylene oxide units and an oil soluble calcium salt of dodecylbenzene sulfonic acid. Hydrophilic lipophilic balance ("HLB") values ranging from 8 to 18 will generally provide good stable emulsions. Emulsion stability can sometimes be improved by adding small amounts of EO-PO block copolymer surfactant.

Solubilizers are surfactants that form micelles in water at concentrations above the critical micelle concentration. The micelles are then able to solubilize or solubilize the water-insoluble material within the hydrophobic portions of the micelles. The type of surfactant commonly used for solubilization is a nonionic surfactant: sorbitan monooleate (sorbitan monooleate), sorbitan monooleate ethoxylate (sorbitan monooleate ethoxylate) and methyl oleate (methyl oleate ester).

Surfactants are sometimes used alone or sometimes in combination with other additives (such as mineral or vegetable oils as adjuvants to spray tank mixtures) to improve the biological performance of the pesticide on the target. The type of surfactant used for bioanhancement (bioenhancement) generally depends on the nature and mode of action of the pesticide. However, they are typically non-ionic, such as alkyl ethoxylates, linear fatty alcohol ethoxylates, fatty amine ethoxylates.

Carriers or diluents in agricultural formulations are materials that are added to pesticides to give products of desired strength. The carrier is generally a substance having a high absorption capacity (absorptive capacity), and the diluent is generally a substance having a low absorption capacity. Carriers and diluents are used in powder formulations, wettable powder formulations, granular formulations and water dispersible granular formulations.

Organic solvents are mainly used in emulsifiable concentrate formulations and ULV formulations and to a lesser extent in granular formulations. Mixtures of solvents are sometimes used. The first main group of solvents are aliphatic paraffinic oils (parafinic oils), such as kerosene or refined paraffins. The second main group and most common solvents include aromatic solvents such as xylene and the higher molecular weight fraction C₉And C₁₀An aromatic solvent. Chlorinated hydrocarbons may be used as co-solvents to prevent crystallization of the pesticide when the formulation is emulsified into water. Sometimes alcohols are used as co-solvents to increase solvent power.

Thickeners or gelling agents are used primarily in suspension concentrate formulations, emulsion formulations and suspoemulsion formulations to modify the rheology or flowability of the liquid and prevent separation or settling of the dispersed particles or droplets. Thickeners, gelling agents and anti-settling agents are generally divided into two categories, namely water-insoluble particles and water-soluble polymers. It is possible to use clays and silica to produce suspension concentrate formulations. Examples of these types of materials include, but are not limited to, montmorillonite, such as bentonite; magnesium aluminum silicate; and activated clay (attapulgite). Water-soluble polysaccharides have been used as thickening-gelling agents for many years. The most commonly used types of polysaccharides are natural extracts of seeds or seaweeds or synthetic derivatives of cellulose. Examples of these types of materials include, but are not limited to, guar gum, locust bean gum (locustbean gum), carrageenan (carrageenam), alginates, methylcellulose, sodium carboxymethylcellulose (SCMC), Hydroxyethylcellulose (HEC). Other types of anti-settling agents are based on destructured starch, polyacrylates, polyvinyl alcohols and polyethylene oxides. Another good anti-settling agent is xanthan gum.

The microorganisms cause spoilage (spoilage) of the formulated product. Preservatives are therefore used to eliminate or reduce the action of microorganisms. Examples of such agents include, but are not limited to, propionic acid and its sodium salt, sorbic acid and its sodium or potassium salt, benzoic acid and its sodium salt, parahydroxybenzoic acid sodium salt, methylparaben, and 1, 2-benzisothiazolin-3-one (BIT).

The presence of surfactants that reduce interfacial tension typically results in foaming of the water-based formulation during the mixing operation when produced and applied by the spray can. To reduce foaming tendency, antifoams are usually added at the production stage or before bottling. In general, there are two types of defoamers, namely silicone and non-silicone. The silicone is typically an aqueous emulsion of polydimethylsiloxane, while the non-silicone antifoam agent is a water-insoluble oil such as octanol and nonanol. In both cases, the function of the defoamer is to displace the surfactant from the air-water interface.

For further information see "Chemistry and Technology of agricultural formulations" edited by D.A. Knowles, copyright 1998by Kluwer academic publishers. See also "antibiotics in Agriculture and environmental-retrospecs and Prospecs" by A.S. Perry, I.Yamamoto, I.Ishaaya, and R.Perry, copy 1998by Springer-Verlag.

Administration of

The actual amount of pesticide applied to the locus of the pest is generally not critical and can be readily determined by one skilled in the art. Generally, concentrations of about 0.01 grams of insecticide per hectare to concentrations of about 5000 grams of insecticide per hectare are expected to provide good control.

The locus to which the pesticide is applied may be any locus occupied by pests, such as vegetable crops, fruit and nut trees, grapevines, ornamentals, livestock, the interior or exterior surfaces of buildings and the soil surrounding buildings. Controlling pests generally means that pest population is reduced, activity is reduced, or both population and activity are reduced in a locus. This may occur when the following occurs: pest populations are repelled from a locus; the partial or complete, temporary or permanent incapacitation of pests in or around a locus; or the pests are wholly or partially exterminated in or around the locus. Combinations of these results can of course occur. Generally, it is desirable that pest population, activity, or both population and activity be reduced by more than fifty percent, preferably more than 90%, and even more preferably 99%.

Generally, in the case of baits, the bait is placed in a location where, for example, termites can come into contact with the bait. The bait may also be applied to surfaces of buildings (horizontal, vertical, or inclined surfaces) where, for example, ants, termites, cockroaches, and flies may come into contact with the bait.

Because of the unique ability of some pest eggs to resist pesticide action, repeated applications may be required to control emerging larvae.

Systemic movement of pesticides in a plant can be used for pest control by applying the pesticide to a different part of the plant and to another part of the plant or to a location where the pesticide is available to the root system of the plant. For example, control of foliar-feeding insects can be achieved by drip irrigation application or furrow application or by treating the seed prior to planting. Seed treatment may be applied to all types of seeds, including seeds that can be grown into plants genetically transformed to express a particular attribute. Representative examples include seeds expressing proteins or other insecticidal toxins toxic to invertebrate pests (e.g., Bacillus thuringiensis), seeds expressing herbicide resistance (e.g., "rounduprady" seeds), or seeds with "stacked" exogenous genes expressing insecticidal toxins, herbicide resistance, nutrient enhancing properties, or any other beneficial properties. Furthermore, said seed treatment with the invention disclosed in this document can further enhance the ability of plants to better withstand stressed growth conditions. This results in healthier, more vigorous plants, and thus higher yields at harvest.

It should be apparent that the present invention may be used with plants genetically transformed to express specific traits (specializedtraits) such as bacillus thuringiensis or other insecticidal toxins, or with plants expressing herbicide resistance, or with plants having "stacked" exogenous genes expressing insecticidal toxins, herbicide resistance, nutrient enhancing properties, or any other beneficial properties. One example of such use is spraying the plants with the invention disclosed in this document.

The invention disclosed in this document is suitable for controlling endoparasites (endo-arasitites) and ectoparasites (ectoarasities) in veterinary medicine or in the field of animal feeding. The compounds according to the invention are applied here in a known manner, such as orally, for example in the form of tablets, capsules, drinks, granules, transdermally, for example in the form of dips, sprays, pours, spots and dusts, and parenterally, for example in the form of injections.

The invention disclosed in this document can also be advantageously used in livestock breeding (e.g., cattle, sheep, pigs, chickens, and geese). Suitable formulations are administered orally to animals along with drinking water or feed. The appropriate dosage and formulation depends on the species.

Before the pesticide can be used or sold commercially, it undergoes lengthy evaluation procedures by various governmental authorities (local, regional, state, national, international). The large data requirements (volitional datarequirement) are specified by the authorities and must be given by data generation (data generation) and submitted by the product registrant or by others on behalf of the product registrant. These governmental authorities then evaluate the data and provide product registration approvals (product registration approvals) to potential users or sellers if security decisions are made. These insecticides can then be used or sold by the user or seller where product registration is authorized and supported.

Headings in this document are for convenience only and are not intended to be used in any way to explain any portion of this document.

Claims (18)

1. A compound having the formula

Wherein

R¹Is an unsubstituted heterocyclic group or a substituted heterocyclic group, wherein the substituted heterocyclic group has one or more substituents independently selected from the group consisting of: alkenyl, alkenyloxy, alkyloxy, alkyl, alkynyl, alkynyloxy, arylCycloalkenyl, cycloalkenyloxy, cycloalkyl, cycloalkyloxy, halogen, haloalkyl, and heterocyclyl;

R²is hydrogen, alkenyl, alkenyloxy, alkyloxy, alkyl, alkynyl, alkynyloxy, aryl, cycloalkenyl, cycloalkenyloxy, cycloalkyl, cycloalkyloxy, halogen, haloalkyl, or heterocyclyl;

R³is hydrogen, alkenyl, alkenyloxy, alkyloxy, alkyl, alkynyl, alkynyloxy, aryl, cycloalkenyl, cycloalkenyloxy, cycloalkyl, cycloalkyloxy, halogen, haloalkyl, or heterocyclyl; or

R²And R³May form a ring containing 3 or more ring atoms, said ring optionally including O or N atoms;

R⁴is hydrogen, alkenyl, alkenyloxy, alkyloxy, alkyl, alkynyl, alkynyloxy, aryl, cycloalkenyl, cycloalkenyloxy, cycloalkyl, cycloalkyloxy, halogen, haloalkyl, heterocyclyl, or when R is⁴And R¹When taken together to form a 4, 5 or 6 membered ring, R⁴Is- (CH)₂)-；

R⁵Is an unsubstituted heterocyclic group or a substituted heterocyclic group, wherein the substituted heterocyclic group has one or more substituents independently selected from the group consisting of: alkenyl, alkenyloxy, alkyloxy, alkyl, alkynyl, alkynyloxy, aryl, cycloalkenyl, cycloalkenyloxy, cycloalkyl, cycloalkyloxy, halogen, haloalkyl, heterocyclyl, and-O^-。

2. A method of controlling pests, which comprises applying a compound of claim 1 to an area where pest control is desired.

3. A compound having the formula

Wherein

R¹Is unsubstitutedA heterocyclic group or a substituted heterocyclic group, wherein the substituted heterocyclic group has one or more substituents independently selected from the group consisting of: alkenyl, alkenyloxy, alkyloxy, alkyl, alkynyl, alkynyloxy, aryl, cycloalkenyl, cycloalkenyloxy, cycloalkyl, cycloalkyloxy, halogen, haloalkyl, and heterocyclyl;

R²is H, alkenyl, alkenyloxy, alkyloxy, alkyl, alkynyl, alkynyloxy, aryl, cycloalkenyl, cycloalkenyloxy, cycloalkyl, cycloalkyloxy, halogen, haloalkyl, or heterocyclyl;

R³is H, alkenyl, alkenyloxy, alkyloxy, alkyl, alkynyl, alkynyloxy, aryl, cycloalkenyl, cycloalkenyloxy, cycloalkyl, cycloalkyloxy, halogen, haloalkyl, or heterocyclyl; or

R²And R³May form a ring containing 3 or more ring atoms, said ring optionally including O or N atoms;

R²and R⁴May form a ring containing 3 or more ring atoms, said ring optionally including O or N atoms; or

R⁴Is H, alkenyl, alkenyloxy, alkyloxy, alkyl, alkynyl, alkynyloxy, aryl, cycloalkenyl, cycloalkenyloxy, cycloalkyl, cycloalkyloxy, halogen, haloalkyl, or heterocyclyl; and

R⁵is an unsubstituted heterocyclic group or a substituted heterocyclic group, wherein the substituted heterocyclic group has one or more substituents independently selected from the group consisting of: alkenyl, alkenyloxy, alkyloxy, alkyl, alkynyl, alkynyloxy, aryl, cycloalkenyl, cycloalkenyloxy, cycloalkyl, cycloalkyloxy, halogen, haloalkyl, heterocyclyl, -O^-、CN、C₁-C₆alkyl-O-C (═ O) -, C₁-C₆alkyl-O-C₁-C₆Alkyl-, C₁-C₆alkylthio-C₁-C₆Alkyl-and NO₂，

Optionally, the substituents on the substituted heterocyclyl (which may be further substituted) are further substituted by one or more substituents independently selected from:alkenyl, alkenyloxy, alkyloxy, alkyl, alkynyl, alkynyloxy, aryl, cycloalkenyl, cycloalkenyloxy, cycloalkyl, cycloalkyloxy, halogen, haloalkyl, heterocyclyl, CN, C₁-C₆alkyl-O-C (═ O) -and NO₂。

4. A method for controlling pests, which comprises applying a compound of claim 3 to an area where pest control is desired.

5. A method which comprises applying a compound of claim 3 to a locus to control pests of the phylum nematoda or arthropoda.

6. A method comprising applying a compound of claim 3 to a locus to control arachnids, synopsis or insecta pests.

7. A method comprising applying a compound of claim 3 to a locus to control the following species of pests: from the orders coleoptera, dermaptera, loenoptera, diptera, hemiptera, homoptera, hymenoptera, isoptera, lepidoptera, mallophaga, orthoptera, phthiraptera, siphonaptera, thysanoptera, acarida, nematoda or synaptophia.

8. A composition comprising a mixture of a compound of claim 3 and at least one pesticide.

9. A composition comprising a mixture of a compound of claim 1 with at least one herbicide, with at least one fungicide, or with at least one herbicide and fungicide.

10. A composition comprising a compound of claim 3, and at least one of: antibacterial, germicide, defoliant, safener, synergist, algicide, attractant, desiccant, pheromone, protectant, avicide, disinfectant, semiochemical, or molluscicide.

11. A composition comprising a compound of claim 3, and at least one of: an acetylcholinesterase inhibitor; a sodium channel modulator; chitin biosynthesis inhibitors; GABA-gated chloride channel antagonists; GABA and glutamate gated chloride channel agonists; an acetylcholine receptor agonist; a MET I inhibitor; mg-stimulated atpase inhibitors; nicotinic acetylcholine receptors; a midgut membrane disruption agent; or oxidative phosphorylation interrupters

12. A composition comprising a compound of claim 3, and at least one of: piperonyl butoxide, synergistic aldehydes, esters, chrysanthemums, sesamins or sulfoxides

13. A composition comprising a compound of claim 3 in the form of: baits, concentrated emulsions, powders, emulsifiable concentrates, fumigants, gels, granules, microencapsulated forms, seed treatments, suspension concentrates, suspoemulsions, tablets, water-soluble liquids, water-dispersible granules, wettable powders or ultra low volume solutions.

14. A method of applying a compound of claim 3 to a seed.

15. A method of applying a compound of claim 3 to a seed that has been genetically transformed to express one or more specific attributes.

16. A method of applying a compound of claim 3 to a genetically transformed plant that has been genetically transformed to express one or more specific traits.

17. A method of orally administering or administering a compound of claim 3 to an animal.

18. A method comprising submitting data relating to a compound of claim 3 to a governmental authority in order to obtain product registration approval for a product comprising a compound of claim 3.