US007960354B2

(12) United States Patent (10) Patent N0.: US 7,960,354 B2 Huang et al. (45) Date of Patent: *Jun. 14, 2011

(54) SYNERGISTIC PESTICIDAL MIXTURES (56) References Cited (75) Inventors: Jim X. Huang, Carmel, IN (US); U.S. PATENT DOCUMENTS Jonathan M. Babcock, Carmel, IN 7,511,149 B2 3/2009 Arndt et al. (US); Thomas Meade, Zionsville, IN 7,705,154 B2 4/2010 Heller et a1. (US); Marc Farrow, Fishers, IN (US) 7,705,156 B2 4/2010 Loso et al. 7,709,648 B2 5/2010 Meyer et a1. Assignee: DoW AgroSciences LLC, Indianapolis, 7,709,649 B2 5/2010 Zhu et al. (73) 7,754,888 B2 7/2010 Loso et al. IN (US) 2005/0228027 A1 10/2005 Zhu et al. 2007/0203191 A1 8/2007 Loso et al. (*) Notice: Subject to any disclaimer, the term of this 2007/0299264 A1 12/2007 Huang et al. patent is extended or adjusted under 35 2008/0033180 A1 2/2008 Renga et al. U.S.C. 154(b) by 264 days. 2008/0058390 A1 3/2008 Loso et al. 2008/0108665 A1 5/2008 Huang et al. This patent is subject to a terminal dis FOREIGN PATENT DOCUMENTS claimer. GB 1307271 A 2/1973 (21) Appl. N0.: 12/150,s01 W0 WO 2006/060029 A 6/2006 (22) Filed: May 1, 2008 OTHER PUBLICATIONS Williams, Trevor et al., Biocontrol Science and Technology, “Is the (65) Prior Publication Data Naturally Derived Insecticide Spinosad Compatible with Insect US 2009/0325892 A1 Dec. 31, 2009 Natural Enemies”, Aug. 2003, vol. 13, No. 15, pp. 459-475.* PCT/US2008/00513, Feb. 23, 2009, DoW AgroSciences LLC, PCT Related US. Application Data International Search Report and Written Opinion. (60) Provisional application No. 60/927,119, ?led on May * cited by examiner 1, 2007. Primary Examiner * Shaojia Anna Jiang Int. Cl. (51) Assistant Examiner * Bahar Schmidtmann A01N 33/02 (2006.01) (74) Attorney, Agent, or Firm * Carl D. Corvin; Craig E. A01N 57/16 (2006.01) Mixan A01N 39/00 (2006.01) A01N 53/10 (2006.01) A01P 7/04 (2006.01) (57) ABSTRACT (52) US. Cl...... 514/28; 514/89; 514/506; 514/615 Synergistic pesticidal mixtures are provided. (58) Field of Classi?cation Search ...... 514/28, 514/89, 506, 615 See application ?le for complete search history. 4 Claims, No Drawings US 7,960,354 B2 1 SYNERGISTIC PESTICIDAL MIXTURES (I) / X CROSS REFERENCE TO RELATED APPLICATIONS

This applications claims priority from US. Provisional application 60/927,119 ?led on May 1, 2007, the entire dis closure of Which is hereby incorporated by reference. Wherein X represents NO2, CN or COOR4; L represents a single bond or R1, S and L taken together FIELD OF THE INVENTION represent a 5- or 6-membered ring; R1 represents methyl or ethyl; The invention disclosed in this document is related to ?eld R2 and R3 independently represent hydrogen, methyl, of pesticides and their use in controlling pests. ethyl, ?uoro, chloro or bromo; n is an integer from 0-3; BACKGROUND OF THE INVENTION Y represents 6-halopyridin-3-yl, 6-(Cl-C4)alkylpyridin-3 yl, 6-halo(Cl-C4)alkylpyridin-3-yl, 6-(Cl-C4)alkoxypyridin 3-yl, 6-halo(C1-C4)alkoxypyridin-3-yl, 2-chlorothiaZol-4-yl, Pests cause millions of human deaths around the World 20 each year. Furthermore, there are more than ten thousand or 3-chloroisoxaZol-5-yl When n:0-3 and L represents a species of pests that cause losses in agriculture. These agri single bond, orY represents hydrogen, Cl-C4 alkyl, phenyl, cultural losses amount to billions of US. dollars each year. 6-halopyridin-3-yl, 6-(Cl-C4)alkylpyridin-3-yl, 6-halo(Cl Termites cause damage to various structures such as homes. C4)alkylpyridin-3-yl, 6-(C1-C4)alkoxypyridin-3-yl, 6-halo These termite damage losses amount to billions of US. dol 25 (Cl-C4)alkoxypyridin-3-yl, 2-chlorothiaZol-4-yl, or 3-chlor lars each year. As ?nal note, many stored food pests eat and oisoxaZol-5-yl When n:0-l and R1, S and L taken together adulterate stored food. These stored food losses amount to represent a 5- or 6-membered ring; and billions of US. dollars each year, but more importantly, R4 represents C l-C3 alkyl. deprive people of needed food. Methods for the preparation of sulfoximines, other than There is an acute need for neW pesticides. Insects are devel 30 those described in Scheme H, have been previously disclosed oping resistance to pesticides in current use. Hundreds of in US Patent Publication 20050228027, Whose teachings are insect species are resistant to one or more pesticides. The incorporated herein. development of resistance to some of the older pesticides, The compounds of formula (Ia), Wherein R1, R2, R3 , R4, X, such as DDT, the carbamates, and the organophosphates, is andY are as previously de?ned and L is a single bond, can be Well knoWn. But resistance has even developed to some of the 35 prepared by the methods illustrated in Scheme A: neWer pesticides. Therefore, a need exists for neW pesticides and particularly for pesticides that have neW modes of action.

Substituents (Non-Exhaustive List) 40

The examples given for the substituents are (except for mCPBA NaN3x halo) non-exhaustive and must not be construed as limiting (A) (B) H2804 the invention disclosed in this document. x 0 NH 0 / “alkoxy” means an alkyl further consisting of a carbon 45 oxygen single bond, for example, methoxy, ethoxy, propoxy, R1 isopropoxy, l-butoxy, 2-butoxy, isobutoxy, tert-butoxy, pen toxy, 2-methylbutoxy, l,l-dimethylpropoxy, hexoxy, hep toxy, octoxy, nonoxy, and decoxy. 50 “alkyl” means an acyclic, saturated, branched or In step a of Scheme A, sul?de of formula (A) is oxidiZed unbranched, substituent consisting of carbon and hydrogen, for example, methyl, ethyl, propyl, isopropyl, l-butyl, 2-bu With meta-chloroperoxybenZoic acid (mCPBA) in a polar tyl, isobutyl, tert-butyl, pentyl, 2-methylbutyl, l,l-dimethyl solvent below 00 C. to provide sulfoxide of formula (B). In propyl, hexyl, heptyl, octyl, nonyl, and decyl. most cases, dichloromethane is the preferred solvent for oxi 55 dation. “halo” means ?uoro, chloro, bromo, and iodo. In step b of Scheme A, sulfoxide (B) is iminated With “haloalkyl” means an alkyl further consisting of, from one sodium aZide in the presence of concentrated sulfuric acid in to the maximum possible number of, identical or different, an aprotic solvent under heating to provide sulfoximine of halos, for example, ?uoromethyl, di?uoromethyl, tri?uorom formula (C). In most cases, chloroform is the preferred sol ethyl, l-?uoromethyl, 2-?uoroethyl, 2,2,2-tri?uoroethyl, 60 vent for this reaction. chloromethyl, trichloromethyl, and l , l ,2,2-tetra?uoroethyl. In step c of Scheme A, the nitrogen of sulfoximine (C) can be either cyanated With cyanogen bromide in the presence of a base, or nitrated With nitric acid in the presence of acetic DETAILED DESCRIPTION OF THE INVENTION anhydride under mildly elevated temperature, or carboxy 65 lated With alkyl (R4) chloroformate in the presence of base Compounds of the folloWing formula are synergistic With a such as 4-dimethylaminopyridine (DMAP) to provide N- sub variety of other pesticides. stituted sulfoximine (Ia). Base is required for e?icient cyana US 7,960,354 B2 3 4 tion and carboxylation and the preferred base is DMAP, The starting sul?des (A) in Scheme A can be prepared in Whereas sulfuric acid is used as catalyst for ef?cient nitration different Ways as illustrated in Schemes D, E, F G, H, and I. reaction. In Scheme D, the sul?de of formula (Al), Wherein R1, R2 The compounds of formula (Ia), Wherein X represents CN and Y are as previously de?ned, n:l, and R3:H, can be and R1, R2, R3, R4 andY are as previously de?ned, can be 5 prepared from the chloride of formula (D1) by nucleophilic prepared by the mild and e?icient method illustrated in substitution With the sodium salt of an alkyl thiol. Scheme B.

3. SchemeD

Rl R2 R2 (A) Y Y RlsNa N/ CN 01 R1 s (D1) (A1) Z 3 b S — L — (CRRh _ Y —>mCPBA,K2CO3 l Or 20 R RuCl3,NaIO4 (F) CN N/ In Scheme E, the sul?de of formula (A2), Wherein R1, R2 and Y are as previously de?ned, n:3, and R3:H, can be 25 prepared from the chloride of formula (D2) by reacting With a 2-mono substituted methyl malonate in the presence of base such as potassium tert-butoxide to provide 2,2-disubstitued malonate, hydrolysis under basic conditions to form a diacid, decarboxylation of the diacid by heating to give a monoacid, In step a of Scheme B, sul?de is oXidiZed With iodobenZene 30 reduction of the monoacid With borane-tetrahyrofuran com diacetate in the presence of cyanamide at 0° C. to give sul?l plex to provide an alcohol, tosylation of the alcohol With imine (F). The reaction can be carried out in a polar aprotic toluenesulfonyl chloride (tosyl chloride) in the presence of a solvent like dichloromethane. base like pyridine to give a tosylate and replacement of the tosylate With the sodium salt of the desired thiol. In step b of Scheme B, the sul?limine (F) is oXidiZed With 35 mCPBA. A base such as potassium carbonate is employed to neutraliZe the acidity of mCPBA. Protic polar solvents such as ethanol and Water are used to increase the solubility of the sul?limine starting material and the base employed. The sul ?limine (F) can also be oxidized With aqueous sodium or 40 Scheme E potassium periodinate solution in the presence of catalyst Y ruthenium trichloride hydrate or similar catalyst. The organic MeOZC solvent for this catalysis can be polar aprotic solvent such as ClCH2—Y —>KOlBu M O C —>LiOH dichloromethane, chloroform, or acetonitrile. (D2) R2CH(CO2Me)2 6 2 R2 45 The ot-carbon of the N-substituted sulfoximine of formula (Ia), i.e., n:l, R3:H in the (CR2R3) group adjacent to the N-substituted sulfoximine function can be further alkylated or halogenated (R5) in the presence of a base such as potas Y Y sium hexamethyldisilamide (KHMDS) to give N-substituted 50 H020 A sulfoximines of formula (lb), Wherein R1, R2, R3, R4, X, L H020 2 BH3-THF andY are as previously de?ned and Z is an appropriate leav R2 R2 ing group, as illustrated in Scheme C. The preferred leaving groups are iodide (R5:alkyl), benZenesulfonimide (R5:F), tetrachloroethene (R5:Cl), and tetra?uoroethene (R5:Br). 55

HO Y TsO Y

Schemell —> —> TsCl, Py NaSRl X X R2 R2 60

| RSZ | | R1 R1 R5 R2 (Ia) (1b) 65 (A2) US 7,960,354 B2 5 6 In Scheme F, the sul?de of formula (A3), Wherein R1, R2 and Y are as previously de?ned, n:2, and R3:H, can be S 1 G prepared from the nitrile of formula (E) by deprotonation With a strong base and alkylation With an alkyl iodide to give m m ot-alkylated nitrile, hydrolysis of the ot-alkylated nitrile in the 5 —>a —>b presence of a strong ac1dl1ke. . HCl to give. an acid,. reduction. of NCS, YMgCl the acid With borane-tetrahydrofuran complex to provide an S S Cl alcohol, tosylation of the alcohol With tosyl chloride in the presence of a base like pyridine to give a tosylate and replace- m ment of the tosylate With the sodium salt of the desired thiol. 10 S Y (A4) SchemeE

R2 15 An alternative method for the preparation of sul?des of /—Y W >~Y $> formula (A4), Wherein R1, S and L taken together form a ring, NC R21 NC n:0, m:0, andY:6-halo, 6-(Cl-C4)alkyl, 6-(Cl-C4)haloalkyl (E) or 6-(Cl-C4)alkoxy‘substituted 3-pyridyl~is highlighted in 20 Scheme H. Accordingly, the corresponding appropriately R2 R2 substituted chloromethyl pyridine is treated With thiourea, Y —> jy —> hydrolyZed and subsequently alkylated With l-bromo-3 -chlo HOZC BH3'THF HO TsCl, Py ropropane under aqueous base conditions,. . and cycliZed. 1n. the presence of a base like potassium tert-butoxide in a polar aprotic solvent such as tetrahydrofuran (THF).

SchemiH

\ Cl thiourea EtOH, 25° C. / sub N

NH

\ SiNHZ l-bromo-B-chlOropropaneNaOH, H2O, 10° c. OASMCII / / sub N sub N

S \ KO’Bu THF, HMPA, 250 c. / N sub (A4)

-Continued 50 In Scheme I, the sul?de of formula (A5), wherein R1 is previously de?ned, L is a bond, n:0 andY is 6-chloropyridin R2 R2 3-yl can be prepared from 2-chloro-5-bromopyridine With a jY NaSRl jY halo-metal?de exchange folloWed by a substitution With disul TsO /s 55 Schemel l R (A3) \ Br BuLi \ S\R1 RlssRl / / 60 01 N 01 N In Scheme G, the sul?de of formula (A4), Wherein R1, S (A5) and L taken together form a ring, n:0, and Y:isopropyl or phenyl can be prepared from the unsubstituted cyclic sul?de Wherein m:0, l. Chlorination of the cyclic sul?de starting Sulfoximine compounds of type Ib Wherein R1, S and L material With N-chlorosuccinimide in benZene folloWed by 65 taken together form a saturated 5- or 6-membered ring and alkylation With Grignard reagent can lead to the desired sul- n:l can be prepared by the methods illustrated in Scheme J ?de (A4) in satisfactory yield. Wherein X andY are as previously de?ned and m is 0 or 1. US 7,960,354 B2 7 8

Scheme J

m 3. m b m c m —> —> NaN3, H2804 BrCN, DMAP Bage S or MSH S Or HNO3/Ac2O S Y — CHZCL S Y H // \\ or CICOZMe, DMAP // \\ J80 C_ // \\ O O NH O N — X 0 N — X lb \ y

m a m —> Y Y S s H // \\ O O NH (A4)

25 In step a of Scheme J, Which is similar to step b of Scheme Example I A, sulfoxide is iminated With sodium aZide in the presence of concentrated sulfuric acid or With O-mesitylsulfonylhy [(6 -Tri?uoromethylpyridin-3 -yl)methyl] (methyl) droxylamine in a polar aprotic solvent to provide sulfox 30 oxido -7t4-sulfanylidenecyanamide (1) imine. Chloroform or dichloromethane are the preferred sol vents. In step b of Scheme J, similar to step c of Scheme A, the nitrogen of sulfoximine can be either cyanated With cyanogen (1) bromide, or nitrated With nitric acid followed by treatment 35 With acetic anhydride under re?uxing conditions, or carboxy lated With methyl chloroformate in the presence of base such N CN. as DMAP to provide N-substituted cyclic sulfoximine. Base is required for e?icient cyanation and carboxylation and the preferred base is DMAP, Whereas sulfuric acid is used as 40 [(6-Tri?uoromethylpyridin-3-yl)methyl](methyl)-oxido catalyst for ef?cient nitration reaction. k4-sulfanylidenecyanamide (1) Was prepared from 3-chlo romethyl-6-(tri?uoromethyl)pyridine according to the fol In step c of Scheme J, the ot-carbon of N-substituted sul foximine can be alkylated With a heteroaromatic methyl loWing three step sequence: halide in the presence of a base such as KHMDS or butyl 45 lithium (BuLi) to give the desired N-substituted sulfox N SCH (A) imines. The preferred halide can be bromide, chloride or \ C1 % iodide. EtOH/HZO, 25° C. Alternatively, the compounds of formula (lb) can be pre / (67%) pared by a ?rst ot-alkylation of sulfoxides to give ot-substi 50 F3C N tuted sulfoxides and then an imination of the sulfoxide fol \ S / CH3 loWed by N-substitution of the resulting sulfoximine by using the steps 0, a and b respectively as described above for / F3C N Scheme J. 55 (A) Compounds in Which Y represents claimed substituents other than 6-(C1-C4)haloalkylpyridin-3-yl and 6-(Cl-C4)ha loalkoxypyridin-3-yl have been disclosed in US Patent Pub To a solution of 3-chloromethyl-6-(tri?uoromethyl)pyri lication 20050228027, Whose teachings are incorporated dine (5.1 g, 26 mmol) in dimethyl sulfoxide (DMSO; 20 mL) herein. 60 Was added in one portion sodium thiomethoxide (1.8 g, 26 mmol). A violent exothermic reaction Was observed Which resulted in the reaction turning dark. The reaction Was stirred EXAMPLES for 1 hr, then additional sodium thiomethoxide (0.91 g, 13 mmol) Was added sloWly. The reaction Was stirred overnight, The examples are for illustration purposes and are not to be 65 after Which it Was poured into H20 and several drops of cone. construed as limiting the invention disclosed in this document HCl Were added. The mixture Was extracted With Et2O (3x50 to only the embodiments disclosed in these examples. mL) and the organic layers combined, Washed With brine, US 7,960,354 B2 10 dried over MgSO4 and concentrated. The crude product Was 2H), 3.2 (s, 3H); LC-MS (ELSD): mass calcd for puri?ed by chromatography (Prep 500, 10% acetone/hex C9H9F3N3OS [M+H]+ 264.04. Found 263.92. anes) to furnish the sul?de (A) as a pale yellow oil (3.6 g, 67%). 1H NMR (300 MHZ, CDCl3): 6 8.6 (s, 1H), 7.9 (d, 1H), Example 11 7.7 (d, 1H), 3.7 (s, 2H), 2.0 (s, 3H); GC-MS: mass calcd for C8H8F3NS [M]+ 207. Found 207. [1-(6 -Tri?uoromethylpyridin-3 -yl)ethyl] (methyl) oxido-7t4-sulfanylidenecyanamide (2) (B) \ S / CH3 HZNCN, PhI(OAc)2 I CH3C13, 0° C. / (14%) (Z) F3C N (A) CH3 I \ ?/ / o N / N F3C N \CN CN (A) (B) 20

To a solution of sul?de (A) (3.5 g, 17 mmol) and cyanamide (1.4 mg, 34 mmol) in dichloromethane (30 mL) at 0° C. Was added iodobenZenediacetate (11.0 g, 34 mmol) all at once. The reaction Was stirred for 30 minutes then alloWed to Warm 25 CH 1. KHMDS, HMPA, to room temperature overnight. The mixture Was diluted With \ S/ 3 THF, -780 C. dichloromethane (50 mL) and Washed With H2O. The aque I //\\ 2. CH3I ous layer Was extracted With ethyl acetate (4x50 mL), and the F C N/ o N—CN (59%) combined dichloromethane and ethyl acetate layers dried 3 30 over MgSO4 and concentrated. The crude product Was tritu (1) rated With hexanes and puri?ed by chromatography (chroma totron, 60% acetone/hexanes) to fumish the sul?limine (B) as a yelloW gum (0.60 g, 14%). IR (?lm) 3008, 2924, 2143, 1693 CH3 cm“; 1H NMR (300 MHZ, CDCl3): 6 8.8 (s, 1H), 8.0 (d, 1H), 35

7.8 (d, 1H), 4.5 (d, 1H), 4.3 (d, 1H), 2.9 (s, 3H); LC-MS (ESI): s /CH3 mass calcd for C9H9F3N3S [M+H]+ 248.04. Found 248. //\\ / o N—CN F3C N (C) 40 (Z)

—> I I'll EtOPUHZO, 0° C. [1 -(6-Tri?uoromethylpyridin-3 -yl)ethyl] (methyl) -oxido (44%) k4-sulfanylidenecyanamide (2) Was prepared from [(6-trif 45 luoromethylpyridin-3 -yl)methyl] -(methyl)-oxido -7»4- sulfa nylidenecyanamide (1) using the method outlined in Scheme C: To a solution of sulfoximine (1) (50 mg, 0.19 mmol) and hexamethylphosphoramide (HMPA; 17 ML, 0.10 mmol) in 50 tetrahydrofuran (THF; 2 mL) at —78° C. Was addedpotassium hexamethyldisilaZane (KHMDS; 0.5 M in toluene, 420 ML, To a solution of m-chloroperbenZoic acid (mCPBA; 80%, 0.21 mmol) dropWise. The solution Was stirred at —78° C. for 1.0 g, 4.9 mmol) in EtOH (10 mL) at 0° C. Was added a an additional 20 min, after Which iodomethane (13 ML, 0.21 mmol) Was added. The reaction Was alloWed to Warm to room solution of KZCO3 (1.4 g, 10 mmol) in H20 (7 mL). The 55 solution Was stirred for 20 min and then a solution of sul?l temperature over the course of 1 hr, after Which it Was imine (B) (0.60 g, 2.4 mmol) in EtOH (20 mL) Was added all quenched With saturated aqueous (aq.) NH4Cl and extracted at once. The reaction Was stirred at 0° C. for 30 min, and then With dichloromethane. The organic layer Was dried over alloWed to Warm to room temperature over the course of 1 hr. Na2SO4, concentrated, and the crude product puri?ed by The reaction Was quenched With aq. sodium bisul?te and the 60 chromatography (chromatotron, 70% acetone/CH2Cl2) to mixture concentrated to remove ethanol. The resulting mix furnish the sulfoximine (2) as a 2:1 mixture of diastereomers ture Was extracted With dichloromethane and the combined (colorless oil; 31 mg, 59%). 1H NMR (300 MHZ, CDCl3): 6 organic layers dried over MgSO4 and concentrated. The crude (major diastereomer) 8.8 (s, 1H), 8.1 (d, 1H), 7.8 (d, 1H), 4.6 product Was puri?ed by chromatography (chromatotron, 50% (q, 1H), 3.0 (s, 3H), 2.0 (d, 3H); (minor diastereomer) 8.8 (s, acetone/hexanes) to furnish the sulfoximine (1) as an off 65 1H), 8.1 (d, 1H), 7.8 (d, 1H), 4.6 (q, 1H), 3.1 (s, 3H), 2.0 (d, White solid (0.28 g, 44%). Mp:135-137° C.; 1H NMR (300 3H); LC-MS (ELSD): mass calcd for C1OH1OF3N3OS MHZ, CDCl3): 6 8.8 (s, 1H), 8.1 (d, 1H), 7.8 (d, 1H), 4.7 (m, [M+H]+ 278.06. Found 278.05. US 7,960,354 B2 1 1 12 Example 111 To a solution of amidine hydrochloride (A) (1.8 g, 6.8 mmol) in H20 (12 mL) at 100 C. Was added 10 N NaOH (0.68 mL, 6.8 mmol), Which resulted in the formation of a White 2-(6-Tri?uoromethylpyridin-3 -yl)-1-oXido-tetrahy precipitate. The suspension Was heated at 1000 C. for 30 min, dro - 1 H- 17t4-thien-1 -ylidenecyanamide (3) then cooledback doWn to 100 C. Additional 10 N NaOH (0.68 mL, 6.8 mmol) Was added, folloWed by 1-bromo-3-chloro propane (0.67 mL, 6.8 mmol) all at once. The reaction Was stirred at room temperature overnight, then extracted With (3) dichloromethane. The combined organic layers Were Washed With brine, dried over NaZSO4 and concentrated to furnish the sul?de (B) as a colorless oil (1.7 g, 96%). No further attempt Was made to purify the product. 1H NMR (300 MHZ, CDCl3): 6 8.6 (s, 1H), 7.8 (d, 1H), 7.6 (d, 1H), 3.8 (s, 2H), 3.6 (t, 2H), 2.6 (t, 2H), 2.0 (quint, 2H).

2- (6 -Tri?uoromethylpyridin-3 -yl) -1 -oXido -tetrahydro - (C) 1H- 1 7t-thien-l -ylidene-cyanamide (3) Was prepared from KO’Bu 3-chloromethyl-6-(tri?uoromethyl)-pyridin according to the 20 | \ S —) 5 step sequence outline below: THF, HMPA, 250 c. / (15%) F3C N

I (A) (B) thiourea —> 25 EtOH, 250 c. (58%)

30 NH F3C N \Si (C)

35

To a suspension of potassium tert-butoxide (1.5 g, 13 mmol) in THF (12 mL) Was added HMPA (1.7 mL, 10 mmol) To a suspension of thiourea (1.2 g, 16 mmol) in EtOH (25 40 mL) Was added a solution of 3-chloromethyl-6-(tri?uorom folloWed by a solution of sul?de (B) (1.8 g, 6.7 mmol) in THF ethyl)pyridine in EtOH (10 mL). The suspension Was stirred (3 mL) dropWise. The reaction Was alloWed to stir at room at room temperature for 2 days, during Which a White precipi temperature overnight, folloWed by concentration and puri? tated formed. The precipitate Was ?ltered to give the desired cation by chromatography (Biotage, 40% EtOAc/hexanes) to amidine hydrochloride as a White solid (2.4 g, 58%). 45 furnish cycliZed product (C) as an orange oil (230 mg, 15%). Mp:186-188o C. No further attempt Was made to purify the 1H NMR (300 MHZ, CDCl3): 6 8.7 (s, 1H), 8.0 (d, 1H), 7.6 (d, product. 1H NMR (300 MHZ, CDCl3): 6 8.9 (bs, 4H), 8.4 (s, 1H), 4.6 (dd, 1H), 3.2 (m, 1H), 3.1 (m, 1H), 2.5 (m, 1H), 2.3 1H), 7.6 (d, 1H), 7.3 (d, 1H), 4.2 (s, 2H); LC-MS (ELSD): (m, 1H), 2.1-1.9 (m, 2H). mass calcd for C8H8F3N3S [M+H]+ 236.05. Found 236.01. 50 (D) (B) HZNCN, PhI(OAc)2 NH \ S o CHZCIZ, 0 c. i l-bromo-3-chloro ro ane 55 / (56%) \ S NHZ P P I NaOH, H2O, 10° c. F3C N / (96%) (C) F3C N (A) 60

/ F3C N

(B) 65 US 7,960,354 B2 13 14 To a solution of sul?de (C) (230 mg, 0.99 mmol) and 7.6 (d, 1H), 5.0 (s, 2H), 3.4 (s, 3H); LC-MS (ELSD): mass cyanamide (83 mg, 2.0 mmol) in dichloromethane (5 mL) at calcd for C8H9ClN3OS [M+H]+ 230. Found 230. 0° C. Was added iodobenZenediacetate (350 mg, 1 .1 mmol) all at once. The reaction Was stirred for 3 hr, then concentrated Example V and the crude product puri?ed by chromatography (chroma totron, 50% acetone/hexanes) to fumish the sul?limine (D) as an orange oil (150 mg, mixture of diastereomers, 56%). 1H [1 -(6-Chloropyridin-3 -yl)ethyl] (methyl)oxido -7»4 NMR (300 MHZ, CDCl3): 6 8.8 (s, 1H), 7.9 (d, 1H), 7.8 (d, sulfanylidenecyanamide (5) 1H), 4.8 (dd, 1H), 3.5 (m, 2H), 2.9-2.7 (m, 2H), 2.6 (m, 1H), 2.3 (m, 1H).

(E) (5)

4> EtOPUHZO, 0° c. (44%)

20 Cl N CN

25 [1 -(6-Chloropyridin-3-yl)ethyl] (methyl)oxido -7»4- sulfa nylidenecyanamide (5) Was prepared from [(6-chloropyridin 3 -yl)methyl] (methyl)oxido -7»4- sulfanylidenecyanamide (4) via the same protocol as described in Example H. The ?nal 30 product, isolated as a 3:2 mixture of diastereomers, Was an off-White solid; mp:155-164° C. LC-MS (ELSD): mass To a solution of mCPBA (80%, 180 mg, 0.82 mmol) in calcd for C9H9ClN3OS [M-H]+ 242. Found 242. The diaste reomers of (5) could be separated by recrystalliZation (2:1 EtOH (3 mL) at 0° C. Was added a solution of KZCO3 (230 MeOH/H2O) and subsequent chromatotron chromatography mg, 1.7 mmol) in H2O (1.5 mL). The solution Was stirred for of the supernate to provide (6) and (7) (Stereochemistry arbi 20 min and then a solution of sul?limine (D) (150 mg, 0.55 trarily assigned). mmol) in EtOH (2 mL) Was added all at once. The reaction Was stirred at 0° C. for 45 min, after Which the solvent Was decanted into a separate ?ask and concentrated to give a White (6) solid. The solid Was slurried in CHCl3, ?ltered, and concen 40 trated to fumish pure sulfoximine (3) as a colorless oil (72 mg, 44%). 1H NMR (300 MHZ, CDCl3): 6 (1.511 mixture of diastereomers) 8.8 (s, 2H), 8.0 (d, 2H), 7.8 (d, 2H), 4.7 (q, 1H), 4.6 (q, 1H), 4.0-3.4 (m, s, 4H), 3.0-2.4 (m, 8H); LC-MS Cl N CN (ELSD): mass calcd for CUHUF3N3OS [M+H]+ 290.06. 45 Found 289.99.

Example IV 50 (7) [(6-Chloropyridin-3-yl)methyl] (methyl)oxido-k4 sulfanylidenecyanamide (4)

55 Cl

Compound (6) Was isolated as a White solid; mp:163-165° 60 C.; 1H NMR (300 MHZ, CDCl3): 6 8.4 (d, 1H), 7.9 (dd, 1H), 7.5 (d, 1H), 4.6 (q, 1H), 3.1 (s, 3H), 2.0 (d, 3H); LC-MS (ELSD): mass calcd for C9Hl lClN3OS [M+H]+, 244. Found [(6-Chloropyridin-3-yl)methyl] (methyl)oxido -7»4- sulfa 244. nylidenecyanamide (4) Was prepared fromi3-chloromethyl Compound (7) Was isolated as a colorless oil; 1H NMR 6-chloropyridine via the same 3 step sequence outline in 65 (300 MHZ, CDCl3) 6 8.4 (d, 1H), 7.9 (dd, 1H), 7.5 (d, 1H), 4.6 Example 1. Product Was a White solid; mp:115-117° C.; 1H (q, 1H), 3.0 (s, 3H), 2.0 (d, 3H); LC-MS (ELSD): mass calcd NMR (300 MHZ, CD3OD/CDCl3) 6 8.5 (d, 1H), 8.0 (dd, 1H), for CHllClN3OS [M+H]+, 244. Found 244. US 7,960,354 B2 15 16 Example VI ing from 3.125 ppm) With 12 ml of a diluent consisting 80 parts of 0.025% TWeen 20 in H20 and 20 parts of acetone: 2-(6-Chloropyridin-3-yl)-1-oxido-tetrahydro-1H MeOH. l7t4-thien-l -ylidenecyanamide (8) Assay 2: Master solutions at 1000 ppm Were made by dissolving technical materials in acetone:MeOH (1:1) at 1 mg/ml. For mixtures betWeen Comp 2 and Comp 3, 4 or 5, 0.047 ml of the master solution from each component Were (3) combined and diluted 32>< With acetone:MeOH (0.094 ml of combination+2.906 ml, resulting in 15 .6 ppm for each ai) and then 5>< With 0.025% TWeen 20 in H20 (12 ml) to obtain a 3.125 ppm solution. For mixtures betWeen Comp 2 and Comp 6 or 7, 0.047 ml of the master solution from Comp 2 and 0.752 ml of the master solution from Comp 6 or 7 Were combined and diluted 3.755>< With acetone:MeOH (0.799 ml of combi nation+2.201 ml solvent, resulting in 15.6 ppm for Comp 2 2-(6 -Chloropyridin-3 -yl)-1-oxido-tetrahydro-1H-17t4 and 250 ppm for Comp 6 or 7) and then 5>< With 0.025% thien-l -ylidenecyanamide (8) Was prepared from 3-chlorom TWeen 20 in H20 (12 ml) to obtain a 3.125 ppm solution for ethyl-6-chloropyridine according to the same ?ve step Comp 2 and a 50 ppm solution for Comp 6 or 7. For non sequence described in Example 111. Product Was a colorless 20 mixtures With Comp 2, 3, 4 or 5, the master solutions Were gum and a 1:1 ratio of diastereomers. Diastereomer 1: IR diluted 64>< With acetone:MeOH (0.047 ml+2.953 ml solvent, (?lm) 3439, 3006, 2949, 2194 cm“; 1H NMR (300 MHZ, resulting in 15.6 ppm) and then 5>< With 0.025% TWeen 20 in CDCl3): 6 8.4 (d, 1H), 7.8 (dd, 1H), 7.4 (d, 1H), 4.6 (dd, 1H), H20 (12 ml) to obtain a 3.125 ppm solution. For non-mix 3.6 (m, 2H), 2.4-2.7 (m, 4H); GC-MS: mass calcd for tures With Comp 6 or 7, the master solutions Were diluted ClOHl lClN3OS [M+H]+ 256. Found 256. Diastereomer 2: IR 25 3.989>< With acetone: MeOH (0.752 ml+2.248 ml solvent, (?lm) 3040, 2926, 2191 cm_l; 1H NMR (300 MHZ, CDCl3): resulting in 250 ppm) and then 5>< With 0.025% TWeen 20 in 6 8.4 (d, 1H), 7.8 (dd, 1H), 7.4 (d, 1H), 4.7 (dd, 1H), 3.8 (ddd, H20 (12 ml) to obtain a 50 ppm solution. For both Mixture 1H), 3.4 (m, 1H), 2.8 (m, 1H), 2.6 (m, 2H), 2.3 (m, 1H); and non-mixture, loWer concentrations (0.78, 0.195, 0.049 GC-MS: mass calcd for C1OH1lClN3OS [M+H]+ 256. Found and 0.012 ppm for Comp 2, 3, 4 and 5; 12.5, 3.125, 0.78 and 256. 30 0.195 for Comp 6 and 7) Were prepared by sequentially dilut Insecticidal Test on Green Peach Aphid (Myzus persicae) ing 4 ml of the higher rate (starting from 3.125 or 50 ppm) Using Mixtures of Sulfoximines and Selected Pesticides With 12 ml of a diluent consisting 80 parts of 0.025% TWeen Dose-response, foliar spray assays Were designed and con 20 in H20 and 20 parts of acetone:MeOH (1 : 1). ducted to evaluate synergic effects of mixtures betWeen the 35 ForbothAssays 1 and 2, cabbage seedlings groWn in3-inch following compounds pots, With 2-3 small (3-5 cm) true leaves, Were used as test substrate. The seedlings Were infested With 20-50 green Compound 1 peach aphids (Wingless adult and nymph) 1 day prior to chemical application. Four seedlings Were used for each treat 40 ment. A hand-held Devilbiss sprayer Was used for spraying a \ S/ solution to both sides of cabbage leaves until runoff. Refer / \\ ence plants (solvent check) Were sprayed With the diluent / O N—CN only. Treated plants Were held in a holding room for three Cl N Compound 2 days at approximately 23° C. and 40% RH prior to grading. 45 Evaluation Was conducted by counting the number of live aphids per plant under a microscope. Insecticidal activity Was s/ measured by using Abbott’ s correction formula: Corrected % // \\ Control:100*(X—Y)/X Where X:No. of live aphids on sol / O N—CN vent check plants Y:No. of live aphids on treated plants. c1:3 N 50 TABLE 1 spinosad, spinetoram, gamma-cyhalothrin, methoxy fenoZide, or chlorpyrifos, on green peach aphid. Results Assay 1: Master solutions at 1000 ppm Were made by % Control of green peach dissolving technical materials in acetone:MeOH (1 :1) at 1 55 Test conc, aphid mg/ml. For a mixture betWeen tWo test compounds, 0.047 ml Com ppm Predicted of the master solution from each component Were combined and diluted 32>< With the acetone:MeOH solvent (0.094 ml of pound Com Com Measured from Colby combination+2.906 ml solvents, resulting in 15.6 ppm for A Compound B A B combination calculation* 60 each ai) and then 5>< With 0.025% TWeen 20 in H20 (12 ml) 1 Spinosad 0.012 0.012 35.7 0.00 to obtain a 3.125 ppm solution. For non-mixtures, the master l Spinosad 0.049 0.049 37.5 0.00 solutions Were diluted 64>< With acetone:MeOH (0.047 l Spinosad 0.195 0.195 40.2 0.00 ml+2.953 ml solvent, resulting in 15 .6 ppm) and then 5>< With l Spinosad 0.78 0.78 69.64 49.6 1 Spinosad 3.13 3.13 93.8 76.8 0.025% TWeen 20 in H20 (12 ml) to obtain a 3.125 ppm 1 Spinetorarn 0.012 0.012 25.5 0.00 solution. For both Mixture and non-mixture, loWer concen 65 l Spinetorarn 0.049 0.049 32.14 0.00 trations (0.78, 0.195, 0.049 and 0.012 ppm) Were prepared by l Spinetorarn 0.195 0.195 33.9 0.00 sequentially diluting 4 ml of the higher concentration (start US 7,960,354 B2 1 7 18 TABLE l-continued It Will be appreciated by those skilled in the art that one stereoisomer may be more active than the others. Individual Results stereoisomers and optically active mixtures may be obtained % Control of green peach by selective synthetic procedures, by conventional synthetic Test conc, aphid procedures using resolved starting materials, or by conven tional resolution procedures. Com- ppm Predicted pound Com Com Measured from Colby Pests A Compound B A B combination calculation* In another embodiment, the invention disclosed in this 1 Spinetoram 0.78 0.78 69.2 64.7 document can be used to control pests. 1 gamma- 0.195 0.195 50.00 0.00 cyhalothrin In another embodiment, the invention disclosed in this 1 gamma- 0.78 0.78 83.04 79.2 document can be used to control pests of the Phylum Nema cyhalothrin toda. 1 Methoxyfenozide 3.13 3 . 13 100.00 75. 89 In another embodiment, the invention disclosed in this 1 Chlorpyrifos 0.78 0.78 73.66 49.55 1 Chlorpyrifos 3.13 3.13 94.64 75.89 document can be used to control pests of the Phylum Arthro 2 Spinosad 0.20 0.20 85.91 69.55 poda. 2 Spinosad 0.78 0.78 100.00 98.18 In another embodiment, the invention disclosed in this 2 Spinetoram 0.20 0.20 76.36 69.55 document can be used to control pests of the Subphylum 2 gamma- 0.78 0.78 100.00 99.77 cyhalothrin 20 Chelicerata. 2 Methoxyfenozide 0.05 0.78 43.18 0.00 In another embodiment, the invention disclosed in this 2 Methoxyfenozide 0.20 3 . 13 67.3 69.55 document can be used to control pests of the Class Arachnida. In another embodiment, the invention disclosed in this *Colby Formula = 100 — ((100 — % control ofcompoundA) X (100 — % control ofcompound 2))/l00 (Colby, S. R. 1967. Calculating synergistic and antagonistic responses ofherbicide document can be used to control pests of the Subphylum combinations. Weeds 15: 20-22) 25 Myriapoda. In another embodiment, the invention disclosed in this Acid & Salt Derivatives, and Solvates document can be used to control pests of the Class Symphyla. In another embodiment, the invention disclosed in this The compounds disclosed in this invention can be in the document can be used to control pests of the Subphylum form of pesticidally acceptable acid addition salts. 30 Hexapoda. By Way of non-limiting example, an amine function can In another embodiment, the invention disclosed in this form salts With hydrochloric, hydrobromic, sulfuric, phos document can be used to control pests of the Class Insecta. phoric, acetic, benZoic, citric, malonic, salicylic, malic, In another embodiment, the invention disclosed in this fumaric, oxalic, succinic, tartaric, lactic, gluconic, ascorbic, document can be used to control Coleoptera (beetles). A maleic, aspartic, benZenesulfonic, methanesulfonic, ethane 35 non-exhaustive list of these pests includes, but is not limited sulfonic, hydroxymethanesulfonic, and hydroxyethane to, Acanlhoscelides spp. (Weevils), Acanlhoscelides obleclus (common bean Weevil), Agrilus planipennis (emerald ash sulfonic, acids. borer), Agrioles spp. (WireWorms), Anoplophora glabripen Additionally, by Way of non-limiting example, an acid nis (Asian longhomed beetle), Anlhonomus spp. (Weevils), function can form salts including those derived from alkali or 40 Anlhonomus grandis (boll Weevil), Aphidius spp., Apion spp. alkaline earth metals and those derived from ammonia and (Weevils), Apogonia spp. (grubs), Alaenius sprelulus (Black amines. Examples of preferred cations include sodium, potas Turgrass Ataenius), Alomaria linearis (pygmy mangold sium, magnesium, and aminium cations. beetle), Aulacophore spp., Bolhynoderes punclivenlris (beet The salts are prepared by contacting the free base form With root Weevil), Bruchus spp. (Weevils), Bruchus pisorum (pea a su?icient amount of the desired acid to produce a salt. The 45 Weevil), Cacoesia spp., Callosobruchus maculalus (southern free base forms may be regenerated by treating the salt With a coW pea Weevil), Carpophilus hemipleras (dried fruit beetle), suitable dilute aqueous base solution such as dilute aqueous Cassida villala, Ceroslerna spp, Ceroloma spp. (chry NaOH, potassium carbonate, ammonia, and sodium bicar someids), Ceroloma Zrifurcala (bean leaf beetle), Ceulorhyn bonate. chus spp. (Weevils), Ceulorhynchus assimilis (cabbage seed As an example, in many cases, a pesticide is modi?ed to a 50 pod Weevil), Ceulorhynchus napi (cabbage curculio), more Water soluble form e.g. 2,4-dichlorophenoxy acetic acid Chaelocnema spp. (chrysomelids), Colaspis spp. (soil dimethyl amine salt is a more Water soluble form of 2,4 beetles), Conoderus scalaris, Conoderus sligmosus, dichlorophenoxy acetic acid a Well knoWn herbicide. Conolrachelus nenuphar (plum curculio), Colinus nilidis The compounds disclosed in this invention can also form (Green June beetle), Crioceris asparagi (asparagus beetle), stable complexes With solvent molecules that remain intact 55 Cryptolesles ferrugineus (rusty grain beetle), Cryptolesles after the non-complexed solvent molecules are removed from pusillus (?at grain beetle), Cryplolesles Zurcicus (Turkish the compounds. These complexes are often referred to as grain beetle), Clenicera spp. (WireWorms), Curculio spp. “solvates”. (Weevils), Cyclocephala spp. (grubs), Cylindrocplurus adspersus (sun?ower stem Weevil), Deporaus marginalus Stereoisomers 60 (mango leaf-cutting Weevil), Dermesles lardarius (larder beetle), Dermesles maculales (hide beetle), Diabrolica spp. Certain compounds disclosed in this invention can exist as (chrysolemids), Epilachna variveslis (Mexican bean beetle), one or more stereoisomers. The various stereoisomers Fauslinus cubae, Hylobius pales (pales Weevil), Hypera spp. include geometric isomers, diastereomers, and enantiomers. (Weevils), Hypera poslica (alfalfa Weevil), Hyperdoes spp. Thus, the compounds disclosed in this invention include race 65 (Hyperodes Weevil), Hypolhenemus hampei (coffee berry mic mixtures, individual stereoisomers, and optically active beetle), Ips spp. (engravers), Lasioderma serricorne (ciga mixtures. rette beetle), Leplinolarsa decemlineala (Colorado potato US 7,960,354 B2 19 20 beetle), Liogenysfulscus, Liogenys suluralis, Lissorhoplrus (chinch bug), Calocoris norvegicus (potato mirid), Cimex oryzophilus (rice water weevil), Lyclus spp. (wood beetles/ hemiplerus (tropical bed bug), Cimex leclularius (bed bug), powder post beetles), Maecolaspisjoliveli, Megascelis spp., Dagberlusfascialus, Dichelopsfurcalus, Dysdercus sulurel Melanolus communis, Meligelhes spp., Meligelhes aeneus lus (cotton stainer), Edessa medilabunda, Eurygasler maura (blossom beetle), Melolonlha melolonlha (common Euro (cereal bug), Euschislus heros, Euschislus servus (brown pean cockchafer), Oberea brevis, Oberea linearis, Orycles stink bug), Helopellis anlonii, Helopellis Zheivora (tea blight rhinoceros (date palm beetle), Oryzaephilus mercalor (mer plantbug), Lagynolomus spp. (stink bugs), Leplocorisa ora chant grain beetle), Oryzaephilus surinamensis (sawtoothed Zorius, Leplocorisa varicornis, Lygus spp. (plant bugs), Lygus grain beetle), Oliorhynchus spp. (weevils), Oulema melano hesperus (western tarnished plant bug), Maconellicoccus hir pus (cereal leaf beetle), Oulema oryzae, Panlomorus spp. sulus, Neurocolpus longiroslris, Nezara viridula (southern (weevils), Phyllophaga spp. (May/June beetle), Phyllophaga green stink bug), Phylocoris spp. (plant bugs), Phylocoris cuyabana, Phyllolrela spp. (chrysomelids), Phynchiles spp., californicus, Phylocoris relalivus, Piezodorus guildingi, Popillia japonica (Japanese beetle), Proslephanus Zruncales Poecilocapsus linealus (fourlinedplant bug), Psallus vaccini (larger grain borer), Rhizoperlha dominica (lesser grain cola, Pseudacysla perseae, Scaplocoris caslanea, and Tri borer), Rhizolrogus spp. (Eurpoean chafer), Rhynchophorus aloma spp. (bloodsucking conenose bugs/kissing bugs). spp. (weevils), Scolylus spp. (wood beetles), Shenophorus In another embodiment, the invention disclosed in this spp. (Billbug), Silona linealus (pea leaf weevil), Silophilus document can be used to control Homoplera(aphids, scales, spp. (grain weevils), Silophilus granaries (granary weevil), white?ies, leafhoppers). A non-exhaustive list of these pests Silophilus oryzae (rice weevil), Slegobium paniceum (drug includes, but is not limited to, Acrylhosiphon pisum (pea store beetle), Tribolium spp. (?our beetles), Tribolium casta 20 aphid), Adelges spp. (adelgids), Aleurodes prolelella (cab neum (red ?our beetle), Tribolium confusum (confused ?our bage white?y), Aleurodicus disperses, Aleurolhrixus?occo beetle), Trogoderma variabile (warehouse beetle), and sus (woolly white?y), Aluacaspis spp., Amrasca bigulella Zabrus Zenebioides. bigulella, Aphrophora spp. (leafhoppers),Aonidiella auranli i In another embodiment, the invention disclosed in this (California red scale), Aphis spp. (aphids), Aphis gossypii document can be used to control Dermaplera(earwigs). 25 (cotton aphid), Aphispomi (apple aphid), Aulacorlhum solani In another embodiment, the invention disclosed in this (foxglove aphid), Bemisia spp. (white?ies), Bemisia argenli document can be used to control Dictyoptera (cockroaches). folii, Bemisia Zabaci (sweetpotato white?y), Brachycolus A non-exhaustive list of these pests includes, but is not lim noxius (Russian aphid), Brachycorynella asparagi (aspara ited to, Blallella germanica (German cockroach), Blalla ori gus aphid), Brevennia rehi, Brevicoryne brassicae (cabbage enlalis (oriental cockroach), Parcoblalla pennylvanica, 30 aphid), Ceroplasles spp. (scales), Ceroplasles rubens (red Periplanela americana (American cockroach), Periplanela wax scale), Chionaspis spp. (scales), Chrysomphalus spp. ausiraloasiae (Australian cockroach), Periplaneia brunnea (scales), Coccus spp. (scales), Dysaphis planiaginea (rosy (brown cockroach), Periplanela fuliginosa (smokybrown apple aphid), Empoasca spp. (leafhoppers), Eriosoma lani cockroach), Pyncoselus suninamensis (Surinam cockroach), gerum (woolly apple aphid), Icerya purchasi (cottony cush and Supella longipalpa (brownbanded cockroach). 35 ion scale), Idioscopus nilidulus (mango leafhopper), Laodel In another embodiment, the invention disclosed in this phax slrialellus (smaller brown planthopper), Lepidosaphes document can be used to control Diptera (true ?ies). A non spp., Macrosiphum spp., Macrosiphum euphorbiae (potato exhaustive list of these pests includes, but is not limited to, aphid), Macrosiphum granarium (English grain aphid), Mac Aedes spp. (mosquitoes), Agromyza ?’onlella (alfalfa blotch rosiphum rosae (rose aphid), Macrosleles quadrilinealus (as leafminer), A gromyza spp. (leaf miner ?ies), Anaslrepha spp. 40 ter leafhopper), Mahanarva ?’imbiolala, Melopolophium (fruit ?ies), Anaslrepha suspensa (Caribbean fruit ?y), dirhodum (rose grain aphid), Miclis longicornis, Myzus per Anopheles spp. (mosquitoes), Balrocera spp. (fruit ?ies), sicae (green peach aphid), Nepholellix spp. (leafhoppers), Baclrocera cucurbilae (melon ?y), Baclrocera dorsalis (ori Nepholellix cinclipes (green leafhopper), Nilaparvala lugens ental fruit ?y), Ceralilis spp. (fruit ?ies), Ceralilis capilala (brown planthopper), Parlaloriapergandii (chaff scale), Par (Mediterranea fruit ?y), Chrysops spp. (deer ?ies), Coclil 45 laloria ziziphi (ebony scale), Peregrinus maidis (corn delpha iomyia spp. (screwworms), Conlarinia spp. (Gall midges), cid), Philaenus spp. (spittlebugs), Phylloxera vilifoliae Culex spp. (mosquitoes), Dasineura spp. (gall midges), (grape phylloxera), Physokermes piceae (spruce bud scale), Dasineura brassicae (cabbage gall midge), Delia spp., Delia Planococcus spp. (mealybugs), Pseudococcus spp. (mealy plalura (seedcom maggot), Drosophila spp. (vinegar ?ies), bugs), Pseudococcus brevipes (pine apple mealybug), Quad Fannia spp. (?lth ?ies), Fannia canicularis (little house ?y), 50 raspidiolus perniciosus (San Jose scale), Rhapalosiphum Fannia scalaris (latrine ?y), Gaslerophilus intestinal is (horse spp. (aphids), Rhapalosiphum maida (corn leaf aphid), bot ?y), Gracillia perseae, Haemalobia irrilans (horn ?y), Rhapalosiphum padi (oat bird-cherry aphid), Saisselia spp. Hylemyia spp. (root maggots), Hypoderma linealum (com (scales), Saisselia oleae (black scale), Schizaphis graminum mon cattle grub), Liriomyza spp. (leafminer ?ies), Liriomyza (greenbug), Silobion avenae (English grain aphid), Sogalella brassica (serpentine leafminer), Melophagus ovinus (sheep 55 furcifera (white-backed planthopper), Therioaphis spp. ked), Musca spp. (muscid ?ies), Musca aulumnalis (face ?y), (aphids), Toumeyella spp. (scales), Toxoplera spp. (aphids), Musca domestica (house ?y), Oeslrus ovis (sheep bot ?y), Trialeurodes spp. (white?ies), Trialeurodes vaporariorum Oscinella fril (frit ?y), Pegomyia belae (beet leafminer), (greenhouse white?y), Trialeurodes abuliloneus (banded Phorbia spp., Psila rosae (carrot rust ?y), Rhagolelis cerasi wing white?y), Unaspis spp. (scales), Unaspis yanonensis (cherry fruit ?y), Rhagolelispomonella (apple maggot), Silo 60 (arrowhead scale), and Zulia enlreriana. diplosis mosellana (orange wheat blossom midge), Slomoxys In another embodiment, the invention disclosed in this calcilrans (stable ?y), Tabanus spp. (horse ?ies), and Zipula document can be used to control Hymenoplera(ants, wasps, spp. (crane ?ies). and bees). A non-exhaustive list of these pests includes, but is In another embodiment, the invention disclosed in this not limited to, Acromyrrmex spp., Alhalia rosae, Alla spp. document can be used to control Hemiptera (true bugs). A 65 (leafcutting ants), Camponolus spp. (carpenter ants), Diprion non-exhaustive list of these pests includes, but is not limited spp. (saw?ies), Formica spp. (ants), Iridomyrmex humilis to, Acroslernum hilare (green stink bug), Blissus leucoplerus (Argentine ant), Monomorium ssp., Monomorium minumum US 7,960,354 B2 21 22 (little black ant), Monomorium pharaonis (Pharaoh ant), orbonalis (eggplant fruit borer), Leucoplera malifoliella, Neodiprion spp. (saW?ies), Pogonomyrmex spp. (harvester Lilhocolleclis spp., Lobesia bolrana (grape fruit moth), Laxa ants), Polisles spp. (paper Wasps), Solenopsis spp. (?re ants), grolis spp. (noctuid moths), Loxagrolis albicosla (Western Tapoinoma sessile (odorous house ant), Telranomorium spp. bean cutWorm), Lymanlria dispar (gypsy moth), Lyonelia (pavement ants), Vespula spp. (yellow jackets), and Xylocopa clerkella (apple leaf miner), Mahasena corbelli (oil palm spp. (carpenter bees). bagWorm), Malacosoma spp. (tent caterpillars), Mameslra In another embodiment, the invention disclosed in this brassicae (cabbage armyWorm), Maruca Zeslulalis (bean pod document can be used to control lsoplera (termites). A non borer), Melisa plana (bagWorm), Mylhimna unipuncla (true exhaustive list of these pests includes, but is not limited to, armyWorm), Neoleucinodes eleganlalis (small tomato borer), Coplolennes spp., Coplolermes curvignalhus, Coplolermes Nymphula depunclalis (rice caseWorm), Operophlhera bru ?’enchii, Coplolermes formosanus (Formosan subterranean mala (Winter moth), Oslrinia nubilalis (European corn termite), Cornilennes spp. (nasute termites), Cryplolennes borer), Oxydia vesulia, Pandemis cerasana (common currant spp. (dryWood termites), Helerolermes spp. (desert subterra tortrix), Pandemis heparana (broWn apple tortrix), Papilio nean termites), Helerolermes aureus, Kalolermes spp. (dry demodocus, Peclinophora gossypiella (pink bollWorm), Wood termites), Incislilermes spp. (dryWood termites), Mac Peridroma spp. (cutWorms), Peridroma saucia (variegated rolennes spp. (fungus growing termites), Marginilermes spp. cutWorm), Perileucoplera co?‘eella (White coffee leafminer), (dryWood termites), Microcerolermes spp. (harvester ter Phlhorimaea operculella (potato tuber moth), Phyllocnisilis mites), Microlermes obesi, Procornilermes spp., Reliculiler cilrella, Phyllonorycler spp. (leafminers), Pieris rapae (im mes spp. (subterranean termites), Reliculilermes banyulensis, ported cabbageWorm), Plalhypena scabra, Plodia inlerpunc Reliculilermes grassei, Reliculilermes?avipes (eastern sub 20 Zella (Indian meal moth), Plulella xyloslella (diamondback terranean termite), Reliculilermes hageni, Reliculilermes moth), Polychrosis vileana (grape berry moth), Prays hesperus (Western subterranean termite), Reliculilermes san endocarpa, Prays 0leae (olive moth), Pseudalelia spp. (noc Zonensis, Reliculilermes speralus, Reliculilermes Zibialis, tuid moths), Pseudalelia unipunclala (armyWorm), Reliculilermes virginicus, Schedorhinolermes spp., and Z00 Pseudoplusia includens (soybean looper), Rachiplusia nu, Zermopsis spp. (rotten-Wood termites). 25 Scirpophaga incerlulas, Sesamia spp. (stemborers), Sesamia In another embodiment, the invention disclosed in this inferens (pink rice stem borer), Sesamia nonagrioides, Selora document can be used to control Lepidoplera (moths and nilens, Silolroga cerealella (Angoumois grain moth), Spar butter?ies). A non-exhaustive list of these pests includes, but ganolhis pilleriana, Spodoplera spp. (armyWorms), is not limited to, Achoea janala, Adoxophyes spp., Adoxo Spodoplera exigua (beet armyWorm), Spodoplerafugiperda phyes orana, Agrolis spp. (cutWorms), Agrolis ipsilon (black 30 (fall armyWorm), Spodoplera oridania (southern army cutWorm), Alabama argillacea (cotton leafWorm), Amorbia Worm), Synanlhedon spp. (root borers), Thecla basilides, cuneana, Amyelosis iransiiella (navel orangeWorm), Ana Thermisia gemmaialis, lineola bisselliella (Webbing clothes camplodes defeclaria, Anarsia linealella (peach tWig borer), moth), Trichoplusia ni (cabbage looper), Tula absolula, Anomis sabulifera (jute looper), Anlicarsia gemmalalis (vel Yponomeula spp., Zeuzera cofeae (red branch borer), and vetbean caterpillar), Archips argyrospila (fruittree leafroller), 35 Zeuzera pyrina (leopard moth). Archips rosana (rose leaf roller), Argyrolaenia spp. (tortricid In another embodiment, the invention disclosed in this moths), Argyrolaenia cilrana (orange tortrix), Aulographa document can be used to control Mallophaga (cheWing lice). gamma, Bonagola cranaodes, Borbo cinnara (rice leaf A non-exhaustive list of these pests includes, but is not lim folder), Bucculalrix Zhurberiella (cotton leafperforator), ited to, Bovicola 0vis (sheep biting louse), Menacanlhus stra Caloplilia spp. (leaf miners), Capua reliculana, Carposina 40 mineus (chicken body louse), and Menopon gallinea (com niponensis (peach fruit moth), Chilo spp., Chlumelia trans mon hen house). versa (mango shoot borer), Chorisloneura rosaceana (ob In another embodiment, the invention disclosed in this liquebanded leafroller), Chrysodeixis spp., Cnaphalocerus document can be used to control Orthoptera (grasshoppers, medinalis (grass leafroller), Colias spp., Conpomorpha locusts, and crickets). A non-exhaustive list of these pests cramerella, Cossus cossus (carpenter moth), Crambus spp. 45 includes, but is not limited to, Anabrus simplex (Mormon (Sod WebWorms), Cydiafunebrana (plum fruit moth), Cydia cricket), Gryllolalpidae (mole crickets), Locusla migraloria, molesla (oriental fruit moth), Cydia nignicana (pea moth), Melanoplus spp. (grasshoppers), Microcenlrum relinerve Cydia pomonella (codling moth), Darna diducla, Diaphania (angularWinged katydid), Plerophylla spp. (kaydids), chislo spp. (stem borers), Dialraea spp. (stalk borers), Dialraea cerca gregaria, Scudderiafurcala (forktailed bush katydid), saccharalis (sugarcane borer), Dialraea graniosella (south 50 and Valanga nigricorni. Wester corn borer), Earias spp. (bollWorms), Earias insulala In another embodiment, the invention disclosed in this (Egyptian bollWorm), Earias vilella (rough northern boll document can be used to control Phthiraptera (sucking lice). Worm), Ecdylopopha auranlianum, Elasmopalpus lignosel A non-exhaustive list of these pests includes, but is not lim lus (lesser cornstalk borer), Epiphysias poslrullana (light ited to, Haemalopinus spp. (cattle and hog lice), Linognalhus broWn apple moth), Epheslia spp. (?our moths), Epheslia 55 ovillus (sheep louse), Pediculus humanus capilis (human caulella (almond moth), Epheslia elulella (tobbaco moth), body louse), Pediculus humanus humanus (human body lice), Epheslia kuehniella (Mediterranean ?our moth), Epimeces and Plhirus pubis (crab louse), spp., Epinolia aporema, Erionola Zhrax (banana skipper), In another embodiment, the invention disclosed in this Eupoecilia ambiguella (grape berry moth), Euxoa auxiliaris document can be used to control Siphonaplera(?eas). A non (army cutWorm), Fellia spp. (cutWorms), Gorzyna spp. (stem 60 exhaustive list of these pests includes, but is not limited to, borers), Grapholila molesla (oriental fruit moth), Hedylepla Clenocephalides canis (dog ?ea), Clenocephalidesfelis (cat indicala (bean leaf Webber), Helicoverpa spp. (noctuid ?ea), and Pulex irrilans (human ?ea). moths), Helicoverpa armigera (cotton bollWorm), Helicov In another embodiment, the invention disclosed in this erpa zea (bollWorm/corn earWorm), Heliolhis spp. (noctuid document can be used to control Thysanoptera (thrips). A moths), Heliolhis virescens (tobacco budWorm), Hellula 65 non-exhaustive list of these pests includes, but is not limited undalis (cabbage WebWorm), Indarbela spp. (root borers), to, Frankliniella fusca (tobacco thrips), Frankliniella occi Keiferia lycopersicella (tomato pinWorm), Leucinodes denlalis (Western ?oWer thrips), Frankliniella shullzei Fran US 7,960,354 B2 23 24 kliniella williamsi (corn thrips), Heliolhrips haemorrhaidalis dathion, aZadirachtin, aZamethiphos, aZinphos ethyl, aZin (greenhouse thrips), Riphiphorolhrips cruenlalus, Scirlo phos methyl, aZobenZene, aZocyclotin, aZothoate, Zhrips spp., Scirlolhrips cilri (citrus thrips), Scirlolhrips dor barium hexa?uorosilicate, barthrin, benclothiaZ, bendio salis (yellow tea thrips), Taeniolhrips rhopalanlennalis, and carb, benfuracarb, benomyl, benoxafos, bensultap, benZoxi Thrips spp. 5 mate, benZyl benZoate, beta cy?uthrin, beta cypermethrin, In another embodiment, the invention disclosed in this bifenaZate, bifenthrin, binapacryl, bioallethrin, bioetha document can be used to control Ihysanura (bristletails). A nomethrin, biopermethrin, bistri?uron, borax, boric acid, non-exhaustive list of these pests includes, but is not limited bromfenvinfos, bromo DDT, bromocyclen, bromophos, bro to, Lepisma spp. (silver?sh) and Thermobia spp. (?rebrats). mophos ethyl, bromopropylate, bufencarb, buprofeZin, In another embodiment, the invention disclosed in this butacarb, butathiofos, butocarboxim, butonate, butoxycar document can be used to control Acarina (mites and ticks). A boxim, non-exhaustive list of these pests includes, but is not limited cadusafos, calcium arsenate, calcium polysul?de, cam to, Acarapsis woodi (tracheal mite of honeybees), Acarus phechlor, carbanolate, carbaryl, carbofuran, carbon disul?de, spp. (food mites), Acarus siro (grain mite), Aceria carbon tetrachloride, carbophenothion, carbosulfan, cartap, mangiferae (mango bud mite), Aculops spp., Aculops lyco chinomethionat, chlorantraniliprole, chlorbenside, chlorbi persici (tomato russet mite), Aculops pelekasi, Aculus pele cyclen, chlordane, chlordecone, chlordimeform, chlore kassi, Aculus schlechlendali (apple rust mite), Amblyomma thoxyfos, chlorfenapyr, chlorfenethol, chlorfenson, chlorfen americanum (lone star tick), Boophilus spp. (ticks), Brevipal sulphide, chlorfenvinphos, chlor?uaZuron, chlormephos, pus obovalus (privet mite), Brevipalpus phoenicis (red and chlorobenZilate, chloroform, chloromebuform, chloromethi black ?at mite), Demodex spp. (mange mites), Dermacenlor 20 uron, chloropicrin, chloropropylate, chlorphoxim, chlorpra spp. (hard ticks), Dermacenlor variabilis (american dog Zophos, chlorpyrifos, chlorpyrifos methyl, chlorthiophos, tick), Dermalophagoides pleronyssinus (house dust mite), chromafenoZide, cinerin I, cinerin II, cismethrin, cloetho Eolelranycus spp., Eolelranychus carpini (yelloW spider carb, clofenteZine, closantel, clothianidin, copper acetoarsen mite), Epilimerus spp., Eriophyes spp., Ixodes spp. (ticks), ite, copper arsenate, copper naphthenate, copper oleate, cou Melalelranycus spp., Noloedres cali, Oligonychus spp., Oli 25 maphos, coumithoate, crotamiton, crotoxyphos, cruentaren gonychus co?‘ee, Oligonychus ilicus (southern red mite), A&B, crufomate, cryolite, cyanofenphos, cyanophos, cyan Panonychus spp., Panonychus cilri (citrus red mite), Panony thoate, cyclethrin, cycloprothrin, cyenopyrafen, cy?u chus ulmi (European red mite), Phyllocoplrula oleivora (cit metofen, cy?uthrin, cyhalothrin, cyhexatin, cypermethrin, rus rust mite), Polyphagolarsonemun lalus (broad mite), Rhi cyphenothrin, cyromaZine, cythioate, picephalus sanguineus (broWn dog tick), Rhizoglyphus spp. 30 d-limonene, daZomet, DBCP, DCIP, DDT, decarbofuran, (bulb mites), Sarcoples scabiei (itch mite), Tegolophus per deltamethrin, demephion, demephion O, demephion S, sea?orae, Tetranychus spp., Tetranychus urticae (tWospotted demeton, demeton methyl, demeton O, demeton 0 methyl, spider mite), and Varroa deslruclor (honey bee mite). demeton S, demeton S methyl, demeton S methylsulphon, In another embodiment, the invention disclosed in this diafenthiuron, dialifos, diamidafos, diaZinon, dicapthon, document can be used to control Nematoda (nematodes). A 35 dichlofenthion, dichlo?uanid, dichlorvos, dicofol, dicresyl, non-exhaustive list of these pests includes, but is not limited dicrotophos, dicyclanil, dieldrin, dienochlor, di?ovidaZin, to, Aphelenchoides spp. (bud and leaf & pine Wood nema di?ubenZuron, dilor, dime?uthrin, dimefox, dimetan, todes), Belonolaimus spp. (sting nematodes), Criconemella dimethoate, dimethrin, dimethylvinphos, dimetilan, dinex, spp. (ring nematodes), Diro?laria immilis (dog heartWom), dinobuton, dinocap, dinocap 4, dinocap 6, dinocton, dinopen Dizylenchus spp. (stem and bulb nematodes), Helerodera spp. 40 ton, dinoprop, dinosam, dinosulfon, dinotefuran, dinoterbon, (cyst nematodes), Helerodera zeae (corn cyst nematode), diofenolan, dioxabenZofos, dioxacarb, dioxathion, diphenyl Hirschmanniella spp. (root nematodes), Hoplolaimus spp. sulfone, disul?ram, disulfoton, dithicrofos, DNOC, (lance nematodes), Meloidogyne spp. (root knot nematodes), dofenapyn, doramectin, Meloidogyne incognila (root knot nematode), Onchocerca ecdysterone, emamectin, EMPC, empenthrin, endosulfan, volvulus (hook-tail Worm), Prazylenchus spp. (lesion nema 45 endothion, endrin, EPN, epofenonane, eprinomectin, esfen todes), Radopholus spp. (burroWing nematodes), and R02); valerate, etaphos, ethiofencarb, ethion, ethiprole, ethoate lenchus reniformis (kidney-shaped nematode). methyl, ethoprophos, ethyl DDD, ethyl formate, ethylene In another embodiment, the invention disclosed in this dibromide, ethylene dichloride, ethylene oxide, etofenprox, document can be used to control Symphyla (symphylans). A etoxaZole, etrimfos, EXD, non-exhaustive list of these pests includes, but is not limited 50 famphur, fenamiphos, fenaZa?or, fenaZaquin, fenbutatin to, Sculigerella immaculala. oxide, fenchlorphos, fenethacarb, fen?uthrin, fenitrothion, For more detailed information consult “Handbook of Pest fenobucarb, fenothiocarb, fenoxacrim, fenoxycarb, fen ControliThe Behavior, Life Histroy, and Control of House pirithrin, fenpropathrin, fenpyroximate, fenson, fensul hold Pests” by Arnold Mallis, 9th Edition, copyright 2004 by fothion, fenthion, fenthion ethyl, fentrifanil, fenvalerate, GIE Media Inc. 55 ?pronil, ?onicamid, ?uacrypyrim, ?uaZuron, ?ubendiamide, ?ubenZimine, ?ucofuron, ?ucycloxuron, ?ucythrinate, ?u Mixtures enetil, ?ufenerim, ?ufenoxuron, ?ufenprox, ?umethrin, ?u orbenside, ?uvalinate, fonofos, formetanate, formothion, Some of the pesticides that can be employed bene?cially in formparanate, fosmethilan, fospirate, fosthiaZate, fosthietan, combination With the invention disclosed in this document 60 fosthietan, furathiocarb, furethrin, furfural, include, but are not limited to the following: gamma cyhalothrin, gamma HCH, 1,2 dichloropropane, 1,3 dichloropropene, halfenprox, halofenoZide, HCH, HEOD, heptachlor, hep abamectin, acephate, acequinocyl, acetamiprid, acethion, tenophos, heterophos, hexa?umuron, hexythiaZox, HHDN, acetoprole, acrinathrin, acrylonitrile, alanycarb, aldicarb, hydramethylnon, hydrogen cyanide, hydroprene, hyquin aldoxycarb, aldrin, allethrin, allosamidin, allyxycarb, alpha 65 carb, cypermethrin, alpha ecdysone, amidithion, amido?umet, imicyafos, imidacloprid, imiprothrin, indoxacarb, aminocarb, amiton, amitraZ, anabasine, arsenous oxide, athi iodomethane, IPSP, isamidofos, isaZofos, isobenZan, isocar US 7,960,354 B2 25 26 bophos, isodrin, isofenphos, isoprocarb, isoprothiolane, molluscicides (these categories not necessarily mutually isothioate, isoxathion, ivermectin exclusive) for reasons of economy, and synergy. jasmolin l, jasmolin ll, jodfenphos, juvenile hormone l, For more information consult “Compendium of Pesticide juvenile hormone ll, juvenile hormone Ill, Common Names” located at http://WWW.alanWood.net/pesti kelevan, kinoprene, cides/index.html as of the ?ling date of this document. Also lambda cyhalothrin, lead arsenate, lepimectin, leptophos, consult “The Pesticide Manual” 14”’ Edition, edited by C D S lindane, lirimfos, lufenuron, lythidathion, Tomlin, copyright 2006 by British Crop Production Council. malathion, malonoben, maZidox, mecarbam, mecarphon, menaZon, mephosfolan, mercurous chloride, mesulfen, Synergistic Mixtures mesulfenfos, meta?umiZone, metam, methacrifos, methami dophos, methidathion, methiocarb, methocrotophos, meth The invention disclosed in this document can be used With omyl, methoprene, methoxychlor, methoxyfenoZide, methyl other compounds such as the ones mentioned under the head ing “Mixtures” to form synergistic mixtures Where the mode bromide, methyl isothiocyanate, methylchloroforrn, methyl of action of the compounds in the mixtures are the same, ene chloride, meto?uthrin, metolcarb, metoxadiaZone, similar, or different. mevinphos, mexacarbate, milbemectin, milbemycin oxime, Examples of mode of actions include, but are not limited to: mipafox, mirex, MNAF, monocrotophos, morphothion, mox acetyl choline esterase inhibitor; sodium channel modulator; idectin, chitin biosynthesis inhibitor; GABA-gated chloride channel naftalofos, naled, naphthalene, nicotine, ni?uridide, nikko antagonist; GABA and glutamate-gated chloride channel mycins, nitenpyram, nithiaZine, nitrilacarb, novaluron, novi 20 agonist; acetyl choline receptor agonist; MET I inhibitor; ?umuron, Mg-stimulated ATPase inhibitor; nicotinic acetylcholine omethoate, oxamyl, oxydemeton methyl, oxydeprofos, receptor; Midgut membrane disrupter; and oxidative phos oxydisulfoton, phorylation disrupter. paradichlorobenZene, parathion, parathion methyl, pen?u Additionally, the folloWing compounds are known as syn ron, pentachlorophenol, permethrin, phenkapton, pheno 25 ergists and can be used With the invention disclosed in this thrin, phenthoate, phorate, phosalone, phosfolan, phosmet, document: piperonyl butoxide, piprotal, propyl isome, sesa phosnichlor, phosphamidon, phosphine, phosphocarb, mex, sesamolin, and sulfoxide. phoxim, phoxim methyl, pirimetaphos, pirimicarb, pirimi phos ethyl, pirimiphos methyl, potassium arsenite, potassium Formulations thiocyanate, pp' DDT, prallethrin, precocene l, precocene ll, 30 precocene Ill, primidophos, proclonol, profenofos, prof A pesticide is rarely suitable for application in its pure luthrin, promacyl, promecarb, propaphos, propargite, pro form. It is usually necessary to add other substances so that petamphos, propoxur, prothidathion, prothiofos, prothoate, the pesticide can be used at the required concentration and in protrifenbute, pyraclofos, pyra?uprole, pyraZophos, pyres an appropriate form, permitting ease of application, handling, methrin, pyrethrin l, pyrethrin ll, pyridaben, pyridalyl, 35 transportation, storage, and maximum pesticide activity. pyridaphenthion, pyri?uquinaZon, pyrimidifen, pyrimitate, Thus, pesticides are formulated into, for example, baits, con pyriprole, pyriproxyfen, centrated emulsions, dusts, emulsi?able concentrates, fumi quassia, quinalphos, quinalphos, quinalphos methyl, gants, gels, granules, microencapsulations, seed treatments, quinothion, quanti?es, suspension concentrates, suspoemulsions, tablets, Water rafoxanide, resmethrin, rotenone, ryania, 40 soluble liquids, Water dispersible granules or dry ?oWables, sabadilla, schradan, selamectin, sila?uofen, sodium arsen Wettable poWders, and ultra loW volume solutions. ite, sodium ?uoride, sodium hexa?uorosilicate, sodium thio For further information on formulation types see “Cata cyanate, sophamide, spinetoram, spinosad, spirodiclofen, logue of pesticide formulation types and international coding spiromesifen, spirotetramat, sulcofuron, sul?ram, sul?ura system” Technical Monograph n02, 5th Edition by CropLife mid, sulfotep, sulfur, sulfuryl ?uoride, sulprofos, 45 International (2002). tau ?uvalinate, taZimcarb, TDE, tebufenoZide, tebufen Pesticides are applied most often as aqueous suspensions pyrad, tebupirimfos, te?ubenZuron, te?uthrin, temephos, or emulsions prepared from concentrated formulations of TEPP, terallethrin, terbufos, tetrachloroethane, tetrachlorvin such pesticides. Such Water-soluble, Water-suspendable, or phos, tetradifon, tetramethrin, tetranactin, tetrasul, theta emulsi?able formulations, are either solids, usually knoWn as cypermethrin, thiacloprid, thiamethoxam, thicrofos, thiocar 50 Wettable poWders, or Water dispersible granules, or liquids boxime, thiocyclam, thiodicarb, thiofanox, thiometon, usually knoWn as emulsi?able concentrates, or aqueous sus thionaZin, thioquinox, thiosultap, thuringiensin, tolfenpyrad, pensions. Wettable poWders, Which may be compacted to tralomethrin, trans?uthrin, transperrnethrin, triarathene, tri form Water dispersible granules, comprise an intimate mix aZamate, triaZophos, trichlorfon, trichlormetaphos 3, trichlo ture of the pesticide, a carrier, and surfactants. The concen ronat, trifenofos, tri?umuron, trimethacarb, triprene, 55 tration of the pesticide is usually from about 10% to about vamidothion, vamidothion, vaniliprole, vaniliprole, 90% by Weight. The carrier is usually chosen from among the XMC, xylylcarb, attapulgite clays, the montmorillonite clays, the diatoma Zeta cypermethrin and Zolaprofos. ceous earths, or the puri?ed silicates. Effective surfactants, Additionally, any combination of the above pesticides can comprising from about 0.5% to about 10% of the Wettable be used. 60 poWder, are found among sulfonated lignins, condensed The invention disclosed in this document can also be used naphthalenesulfonates, naphthalenesulfonates, alkylbenZe With herbicides and fungicides, both for reasons of economy nesulfonates, alkyl sulfates, and nonionic surfactants such as and synergy. ethylene oxide adducts of alkyl phenols. The invention disclosed in this document can be used With Emulsi?able concentrates of pesticides comprise a conve antimicrobials, bactericides, defoliants, safeners, synergists, 65 nient concentration of a pesticide, such as from about 50 to algaecides, attractants, desiccants, pheromones, repellants, about 500 grams per liter of liquid dissolved in a carrier that animal dips, avicides, disinfectants, semiochemicals, and is either a Water miscible solvent or a mixture of Water US 7,960,354 B2 27 28 immiscible organic solvent and emulsi?ers. Useful organic ing factors in the processing, microcapsules can be formed of solvents include aromatics, especially xylenes and petroleum various siZes, solubility, Wall thicknesses, and degrees of fractions, especially the high-boiling naphthalenic and ole penetrability. These factors govern the speed With Which the ?nic portions of petroleum such as heavy aromatic naphtha. active ingredient Within is released, Which. in turn, affects the Other organic solvents may also be used, such as the terpenic residual performance, speed of action, and odor of the prod solvents including rosin derivatives, aliphatic ketones such as uct. cyclohexanone, and complex alcohols such as 2-ethoxyetha Oil solution concentrates are made by dissolving pesticide nol. Suitable emulsi?ers for emulsi?able concentrates are in a solvent that Will hold the pesticide in solution. Oil solu chosen from conventional anionic and nonionic surfactants. tions of a pesticide usually provide faster knockdoWn and kill Aqueous suspensions comprise suspensions of Water-in of pests than other formulations due to the solvents them soluble pesticides dispersed in an aqueous carrier at a con selves having pesticidal action and the dissolution of the centration in the range from about 5% to about 50% by Waxy covering of the integument increasing the speed of Weight. Suspensions are prepared by ?nely grinding the pes uptake of the pesticide. Other advantages of oil solutions ticide and vigorously mixing it into a carrier comprised of include better storage stability, better penetration of crevices, Water and surfactants. Ingredients, such as inorganic salts and and better adhesion to greasy surfaces. synthetic or natural gums, may also be added, to increase the Another embodiment is an oil-in-Water emulsion, Wherein density and viscosity of the aqueous carrier. It is often most the emulsion comprises oily globules Which are each pro effective to grind and mix the pesticide at the same time by vided With a lamellar liquid crystal coating and are dispersed preparing the aqueous mixture and homogenizing it in an in an aqueous phase, Wherein each oily globule comprises at implement such as a sand mill, ball mill, or piston-type 20 least one compound Which is agriculturally active, and is homogeniZer. individually coated With a monolamellar or oligolamellar Pesticides may also be applied as granular compositions layer comprising: (1) at least one non-ionic lipophilic sur that are particularly useful for applications to the soil. Granu face-active agent, (2) at least one non-ionic hydrophilic sur lar compositions usually contain from about 0.5% to about face-active agent and (3) at least one ionic surface-active 10% by Weight of the pesticide, dispersed in a carrier that 25 agent, Wherein the globules having a mean particle diameter comprises clay or a similar substance. Such compositions are of less than 800 nanometers. Further information on the usually prepared by dissolving the pesticide in a suitable embodiment is disclosed in US. patent publication solvent and applying it to a granular carrier Which has been 20070027034 published Feb. 1, 2007, having patent applica pre-formed to the appropriate particle siZe, in the range of tion Ser. No. 11/495,228. For ease of use this embodiment from about 0.5 to 3 mm. Such compositions may also be 30 Will be referred to as For further information consult “Insect formulated by making a dough or paste of the carrier and Pest Management” 2'” Edition by D. Dent, copyright CAB compound and crushing and drying to obtain the desired International (2000). Additionally, for more detailed informa granular particle siZe. tion consult “Handbook of Pest ControliThe Behavior, Life Dusts containing a pesticide are prepared by intimately Histroy, and Control of Household Pests” by Arnold Mallis, mixing the pesticide in poWdered form With a suitable dusty 35 9th Edition, copyright 2004 by GIE Media Inc. agricultural carrier, such as kaolin clay, ground volcanic rock, and the like. Dusts can suitably contain from about 1% to Other Formulation Components about 10% of the pesticide. They can be applied as a seed dressing, or as a foliage application With a dust bloWer Generally, the invention disclosed in this document When machine. 40 used in a formulation, such formulation can also contain other It is equally practical to apply a pesticide in the form of a components. These components include, but are not limited solution in an appropriate organic solvent, usually petroleum to, (this is a non-exhaustive and non-mutually exclusive list) oil, such as the spray oils, Which are Widely used in agricul Wetters, spreaders, stickers, penetrants, buffers, sequestering tural chemistry. agents, drift reduction agents, compatibility agents, anti Pesticides can also be applied in the form of an aerosol 45 foam agents, cleaning agents, and emulsi?ers. A feW compo composition. In such compositions the pesticide is dissolved nents are described forthWith. or dispersed in a carrier, Which is a pressure-generating pro A Wetting agent is a substance that When added to a liquid pellant mixture. The aerosol composition is packaged in a increases the spreading or penetration poWer of the liquid by container from Which the mixture is dispensed through an reducing the interfacial tension betWeen the liquid and the atomiZing valve. 50 surface on Which it is spreading. Wetting agents are used for Pesticide baits are formed When the pesticide is mixed With tWo main functions in agrochemical formulations: during food or an attractant or both. When the pests eat the bait they processing and manufacture to increase the rate of Wetting of also consume the pesticide. Baits may take the form of gran poWders in Water to make concentrates for soluble liquids or ules, gels, ?oWable poWders, liquids, or solids. They are use in suspension concentrates; and during mixing of a product With pest harborages. 55 Water in a spray tank to reduce the Wetting time of Wettable Fumigants are pesticides that have a relatively high vapor poWders and to improve the penetration of Water into Water pressure and hence can exist as a gas in su?icient concentra dispersible granules. Examples of Wetting agents used in tions to kill pests in soil or enclosed spaces. The toxicity of the Wettable poWder, suspension concentrate, and Water-dispers fumigant is proportional to its concentration and the expo sure ible granule formulations are: sodium lauryl sulphate; sodium time. They are characterized by a good capacity for diffusion 60 dioctyl sulphosuccinate; alkyl phenol ethoxylates; and ali and act by penetrating the pest’s respiratory system or being phatic alcohol ethoxylates. absorbed through the pest’s cuticle. Fumigants are applied to A dispersing agent is a substance Which adsorbs onto the control stored product pests under gas proof sheets, in gas surface of a particles and helps to preserve the state of dis sealed rooms or buildings or in special chambers. persion of the particles and prevents them from reaggregat Pesticides can be microencapsulated by suspending the 65 ing. Dispersing agents are added to agrochemical formula pesticide particles or droplets in plastic polymers of various tions to facilitate dispersion and suspension during types. By altering the chemistry of the polymer or by chang manufacture, and to ensure the particles redisperse into Water US 7,960,354 B2 29 30 in a spray tank. They are Widely used in Wettable powders, matic solvents such as xylene and higher molecular Weight suspension concentrates and Water-dispersible granules. Sur fractions of C9 and C10 aromatic solvents. Chlorinated hydro factants that are used as dispersing agents have the ability to carbons are useful as cosolvents to prevent crystallization of adsorb strongly onto a particle surface and provide a charged pesticides When the formulation is emulsi?ed into Water. or steric barrier to reaggregation of particles. The most com 5 Alcohols are sometimes used as cosolvents to increase sol monly used surfactants are anionic, non-ionic, or mixtures of vent poWer. the tWo types. For Wettable poWder formulations, the most Thickeners or gelling agents are used mainly in the formu common dispersing agents are sodium lignosulphonates. For lation of suspension concentrates, emulsions and suspoemul suspension concentrates, very good adsorption and stabiliZa sions to modify the rheology or How properties of the liquid tion are obtained using polyelectrolytes, such as sodium and to prevent separation and settling of the dispersed par naphthalene sulphonate formaldehyde condensates. ticles or droplets. Thickening, gelling, and anti-settling Tristyrylphenol ethoxylate phosphate esters are also used. agents generally fall into tWo categories, namely Water-in Non-ionics such as alkylarylethylene oxide condensates and soluble particulates and Water-soluble polymers. It is possible EO-PO block copolymers are sometimes combined With to produce suspension concentrate formulations using clays anionics as dispersing agents for suspension concentrates, In and silicas. Examples of these types of materials, include, but recent years, neW types of very high molecular Weight poly are limited to, montmorillonite, e.g. bentonite; magnesium meric surfactants have been developed as dispersing agents. aluminum silicate; and attapulgite. Water-soluble polysac These have very long hydrophobic ‘backbones’ and a large charides have been used as thickening-gelling agents for number of ethylene oxide chains forming the ‘teeth’ of a many years. The types of polysaccharides most commonly ‘comb’ surfactant. These high molecular Weight polymers 20 used are natural extracts of seeds and seaWeeds or are syn can give very good long-term stability to suspension concen thetic derivatives of cellulose. Examples of these types of trates because the hydrophobic backbones have many anchor materials include, but are not limited to, guar gum; locust ing points onto the particle surfaces. Examples of dispersing bean gum; carrageenam; alginates; methyl cellulose; sodium agents used in agrochemical formulations are: sodium ligno carboxymethyl cellulose (SCMC); hydroxyethyl cellulose sulphonates; sodium naphthalene sulphonate formaldehyde 25 (HEC). Other types of anti-settling agents are based on modi condensates; tristyrylphenol ethoxylate phosphate esters; ali ?ed starches, polyacrylates, polyvinyl alcohol and polyethyl phatic alcohol ethoxylates; alky ethoxylates; EO-PO block ene oxide. Another good anti-settling agent is xanthan gum. copolymers; and graft copolymers. Microorganisms Which cause spoilage of formulated prod An emulsifying agent is a substance Which stabiliZes a ucts. Therefore preservation agents are used to eliminate or suspension of droplets of one liquid phase in another liquid 30 reduce their effect. Examples of such agents include, but are phase. Without the emulsifying agent the tWo liquids Would limited to. propionic acid and its sodium salt; sorbic acid and separate into tWo immiscible liquid phases. The most com its sodium or potassium salts; benZoic acid and its sodium monly used emulsi?er blends contain alkylphenol or aliphatic salt; p-hydroxy benZoic acid sodium salt; methyl p-hydroxy alcohol With 12 or more ethylene oxide units and the oil benZoate; and l,2-benZisothiaZalin-3-one (BIT). soluble calcium salt of dodecylbenZene sulphonic acid. A 35 The presence of surfactants, Which loWer interfacial ten range of hydrophile-lipophile balance (“HLB”) values from 8 sion, often causes Water-based formulations to foam during to 18 Will normally provide good stable emulsions. Emulsion mixing operations in production and in application through a stability can sometimes be improved by the addition of a spray tank. In order to reduce the tendency to foam, anti-foam small amount of an EO-PO block copolymer surfactant. agents are often added either during the production stage or A solubiliZing agent is a surfactant Which Will form 40 before ?lling into bottles. Generally, there are tWo types of micelles in Water at concentrations above the critical micelle anti-foam agents, namely silicones and non-silicones. Sili concentration. The micelles are then able to dissolve or solu cones are usually aqueous emulsions of dimethyl polysilox biliZed Water-insoluble materials inside the hydrophobic part ane While the non-silicone anti-foam agents are Water-in of the micelle. The type of surfactants usually used for solu soluble oils, such as octanol and nonanol, or silica. In both biliZation are non-ionics: sorbitan monooleates; sorbitan 45 cases, the function of the anti-foam agent is to displace the monooleate ethoxylates; and methyl oleate esters. surfactant from the air-Water interface. Surfactants are sometimes used, either alone or With other For further information see “Chemistry and Technology of additives such as mineral or vegetable oils as adjuvants to Agrochemical Formulations” edited by D. A. Knowles, copy spray-tank mixes to improve the biological performance of right 1998 by KluWer Academic Publishers. Also see “Insec the pesticide on the target. The types of surfactants used for 50 ticides in Agriculture and EnvironmentiRetrospects and bioenhancement depend generally on the nature and mode of Prospects” by A. S. Perry, I. Yamamoto, I. Ishaaya, and R. action of the pesticide. HoWever, they are often non-ionics Perry, copyright 1998 by Springer-Verlag. such as: alky ethoxylates; linear aliphatic alcohol ethoxy lates; aliphatic amine ethoxylates. Applications A carrier or diluent in an agricultural formulation is a 55 material added to the pesticide to give a product of the The actual amount of pesticide to be applied to loci of pests required strength. Carriers arc usually materials With high is not critical and can readily be determined by those skilled absorptive capacities, While diluents are usually materials in the art. In general, concentrations from about 0.01 grams of With loW absorptive capacities. Carriers and diluents are used pesticide per hectare to about 5000 grams of pesticide per in the formulation of dusts, Wettable poWders, granules and 60 hectare are expected to provide good control. Water-dispersible granules. The locus to Which a pesticide is applied can be any locus Organic solvents are used mainly in the formulation of inhabited by an pest, for example, vegetable crops, fruit and emulsi?able concentrates, ULV formulations, and to a lesser nut trees, grape vines, ornamental plants, domesticated ani extent granular formulations. Sometimes mixtures of sol mals, the interior or exterior surfaces of buildings, and the soil vents are used. The ?rst main groups of solvents are aliphatic 65 around buildings. paraf?nic oils such as kerosene or re?ned para?ins. The sec Generally, With baits, the baits are placed in the ground ond main group and the most common comprises the aro Where, for example, termites can come into contact With the US 7,960,354 B2 31 32 bait. Baits can also be applied to a surface of a building, The invention disclosed in this document can also be used (horizontal, vertical, or slant, surface) Where, for example, Before a pesticide can be used or sold commercially, such ants, termites, cockroaches, and ?ies, can come into contact pesticide undergoes lengthy evaluation processes by various With the bait. governmental authorities (local, regional, state, national, Because of the unique ability of the eggs of some pests to international).Voluminous data requirements are speci?ed by resist pesticides repeated applications may be desirable to regulatory authorities and must be addressed through data control neWly emerged larvae. generation and submission by the product registrant or by Systemic movement of pesticides in plants may be utiliZed another on the product registrant’s behalf. These governmen to control pests on one portion of the plant by applying the tal authorities then revieW such data and if a determination of pesticides to a different portion of the plant. For example, safety is concluded, provide the potential user or seller With control of foliar-feeding insects can be controlled by drip product registration approval. Thereafter, in that locality irrigation or furroW application, or by treating the seed before Where the product registration is granted and supported, such planting. Seed treatment can be applied to all types of seeds, user or seller may use or sell such pesticide. including those from Which plants genetically transformed to The headings in this document are for convenience only express specialiZed traits Will germinate. Representative and must not be used to interpret any portion thereof. examples include those expressing proteins toxic to inverte brate pests, such as Bacillus thuringiensis or other insecticidal What is claimed is: toxins, those expressing herbicide resistance, such as 1. A process comprising applying a synergistic composi “Roundup Ready” seed, or those With “stacked” foreign tion comprising a mixture of genes expressing insecticidal toxins, herbicide resistance, 20 nutrition-enhancement or any other bene?cial traits. Further more, such seed treatments With the invention disclosed in this document can further enhance the ability of a plant to better Withstand stressful groWing conditions. This results in a healthier, more vigorous plant, Which can lead to higher 25 yields at harvest time. / o N—CN The invention disclosed in this document is suitable for c1:3 N controlling endoparasites and ectoparasites in the veterinary medicine sector or in the ?eld of animal keeping. Compounds and one or more of the folloWing compounds spinetoram, according to the invention are applied here in a knoWn man 30 gamma-cyhalothrin, methoxyfenoZide, chlorpyrifos, or spi ner, such as by oral administration in the form of, for example, nosad, to a locus to control pests. tablets, capsules, drinks, granules, by dermal application in 2. A process of applying a composition of claim 1 to a seed. the form of, for example, dipping, spraying, pouring on, spot 3. A process of applying a composition of claim 1 to a seed ting on, and dusting, and by parenteral administration in the that has been genetically transformed to express one or more form of, for example, an injection. 35 specialiZed traits. The invention disclosed in this document can also be 4. A process of applying a composition of claim 1 to a employed advantageously in livestock keeping, for example, genetically transformed plant that has been genetically trans cattle, sheep, pigs, chickens, and geese. Suitable formulations formed to express one or more specialiZed traits. are administered orally to the animals With the drinking Water or feed. The dosages and formulations that are suitable 40 depend on the species.