USOO8349815B2

(12) United States Patent (10) Patent No.: US 8,349,815 B2 Huang et al. (45) Date of Patent: *Jan. 8, 2013

(54) SYNERGISTIC PESTICIDAL MIXTURES 4,747,871 A 5/1988 Ruminski et al. 4,833,158 A 5/1989 Twydell et al. Inventors: 4.948,896 A 8/1990 Nagao (75) Jim X. Huang, Carmel, IN (US); 4,973,695 A 11/1990 Yamashita et al. Jonathan M. Babcock, Carmel, IN 5,053,516 A 10, 1991 Hartmann et al. (US); Thomas Meade, ZionZville, IN 5,099,023 A 3, 1992 Miller et al. (US); Marc Farrow, Fishers, IN (US) 5,099,024 A 3, 1992 Pulwer et al. 5,118.809 A 6/1992 Cevasco et al. Assignee: Dow AgroSciences, LLC, Indianapolis, 5,124.458 A 6/1992 Cevasco et al. (73) 5,169,432 A 12/1992 Auinbauh et al. IN (US) 5,225,560 A 7/1993 Cevasco et al. 5,227.491 A 7/1993 Doehner, Jr. (*) Notice: Subject to any disclaimer, the term of this 5,229,519 A 7/1993 Zhang et al. patent is extended or adjusted under 35 6,060,502 A 5, 2000 Lowder et al. U.S.C. 154(b) by 0 days. 7,511,149 B2 3/2009 Arndt et al. 7,541,469 B2 6/2009 Renga et al. This patent is Subject to a terminal dis 7,604.815 B2 10/2009 Loso et al. claimer. 7,678,920 B2 3/2010 Zhu et al. 7,687,634 B2 * 3/2010 Loso et al...... 546,330 7,897,630 B2 * 3/2011 Lahm et al...... 514,378 (21) Appl. No.: 13/096,218 2003/0078430 A1 4/2003 Satake et al. 2004/O158067 A1 8/2004 Hutchison et al. (22) Filed: Apr. 28, 2011 2006, O199964 A1 9/2006 Jackson et al. 2007/02O3191, A1 8, 2007 Loso et al. (65) Prior Publication Data 2007/0249837 A1 10, 2007 Gebhardt et al. 2007/0299264 Al 12/2007 Huang et al. US 2011 FO2OO684 A1 Aug. 18, 2011 2008. O108665 A1 5/2008 Huang et al. 2008. O108666 A1 5/2008 LOSo et al. 2008. O108667 A1 5/2008 Zhu et al. Related U.S. Application Data 2008/O132705 A1 6/2008 Heller et al. (62) Division of application No. 12/150,801, filed on May 2008. O1948.30 A1 8/2008 Meyer et al. 2008/0280915 A1 11/2008 LOSo et al. 1, 2008, now Pat. No. 7,960,354. 2010/0179099 A1* 7, 2010 LOSo et al...... 514, 28 (60) Provisional application No. 60/927,119, filed on May 1, 2007. OTHER PUBLICATIONS "Synergy', medical dictionary provided by thefreedictionary.com; (51) Int. C. also available at http://medical-dictionary.thefreedictionary.com/p/ A6 IK3I/675 (2006.01) synergy; last viewed Nov. 7, 2011.* A6 IK3I/44 (2006.01) Ahmad, Mushtaq, Pesticide Biochemistry and Physiology, Potentia AOIN 57/24 (2006.01) tion/antagonism of deltamethrin and cypermethrins with AOIN 53/08 (2006.01) organophosphate insecticides in the cotton bollworm, Helicoverpa AOIN 43/40 (2006.01) armigera (Lepidoptera: Noctuidae), 2004, vol. 80, pp. 31-42.* (52) U.S. Cl...... 514/89: 514/357 (58) Field of Classification Search ...... None * cited by examiner See application file for complete search history. Primary Examiner — Leigh Maier (56) References Cited Assistant Examiner — Bahar Craigo (74) Attorney, Agent, or Firm — Carl D. Corvin U.S. PATENT DOCUMENTS 3,711,486 A 1, 1973 Torba et al. (57) ABSTRACT 3,787,420 A 1, 1974 Torba et al. 3,852,279 A 12, 1974 Krapcho et al. Synergistic pesticidal mixtures are provided. 4,577,028 A 3, 1986 Martin et al. 4,692, 184 A 9, 1987 Lee 5 Claims, No Drawings US 8,349,815 B2 1. SYNERGISTC PESTICIDAL MIXTURES (I) Y X CROSS REFERENCE TO RELATED N APPLICATIONS o=i-i-CRR-y This applications claims priority from U.S. Provisional application 60/927,119 filed on May 1, 2007, the entire dis closure of which is hereby incorporated by reference. This application also claim priority from U.S. non-provisional wherein 10 X represents NO, CN or COOR: application Ser. No. 12/150,801 filed May 1, 2008, the entire L represents a single bond or R', S and L taken together disclosure of which is hereby incorporated by reference. represent a 5- or 6-membered ring; R" represents methyl or ethyl; FIELD OF THE INVENTION R° and R independently represent hydrogen, methyl, 15 ethyl, fluoro, chloro or bromo: The invention disclosed in this document is related to field n is an integer from 0-3: of pesticides and their use in controlling pests. Y represents 6-halopyridin-3-yl, 6-(C-C)alkylpyridin-3- y1, 6-halo(C-C) alkylpyridin-3-yl, 6-(C-C)alkoxypyri BACKGROUND OF THE INVENTION din-3-yl, 6-halo(C-C)alkoxypyridin-3-yl, 2-chlorothiazol 4-yl, or 3-chloroisoxazol-5-yl when n=0-3 and L represents a Pests cause millions of human deaths around the world single bond, or Y represents hydrogen, C-C alkyl, phenyl, each year. Furthermore, there are more than ten thousand 6-halopyridin-3-yl, 6-(C-C)alkylpyridin-3-yl, 6-halo(C- species of pests that cause losses in agriculture. These agri C.)alkylpyridin-3-yl, 6-(C-C)alkoxypyridin-3-yl, 6-halo cultural losses amount to billions of U.S. dollars each year. (C-C)alkoxypyridin-3-yl, 2-chlorothiazol-4-yl, or 3-chlor Termites cause damage to various structures such as homes. 25 oisoxazol-5-yl when n=0-1 and R', S and L taken together These termite damage losses amount to billions of U.S. dol represent a 5- or 6-membered ring; and lars each year. As final note, many stored food pests eat and R" represents C-C alkyl. adulterate stored food. These stored food losses amount to Methods for the preparation of sulfoximines, other than billions of U.S. dollars each year, but more importantly, those described in Scheme H, have been previously disclosed deprive people of needed food. 30 in US Patent Publication 20050228027, whose teachings are There is an acute need for new pesticides. Insects are devel incorporated herein. oping resistance to pesticides in current use. Hundreds of The compounds of formula (Ia), wherein R',R,R,R, X, insect species are resistant to one or more pesticides. The and Y are as previously defined and L is a single bond, can be development of resistance to some of the older pesticides, prepared by the methods illustrated in Scheme A: Such as DDT, the carbamates, and the organophosphates, is 35 well known. But resistance has even developed to some of the newer pesticides. Therefore, a need exists for new pesticides Scheme A and particularly for pesticides that have new modes of action. 8. R-S-(CRR)Y mCPBA-- Substituents (Non-Exhaustive List) 40 (A) O b The examples given for the substituents are (except for RI-S-(CR2R3)Y - - NaH3, H2SO4 halo) non-exhaustive and must not be construed as limiting (B) the invention disclosed in this document. 45 O NH 'alkoxy' means an alkyl further consisting of a carbon R-S\/ (CRR)Y -->C oxygen single bond, for example, methoxy, ethoxy, propoxy, (C) BrCN, DMAP or isopropoxy, 1-butoxy, 2-butoxy, isobutoxy, tert-butoxy, pen HNO3, AcO or toxy, 2-methylbutoxy, 1,1-dimethylpropoxy, hexoxy, hep CICOR, DMAP toxy, octoxy, nonoxy, and decoxy. 50 -X 'alkyl means an acyclic, Saturated, branched or O N V / 23 unbranched, Substituent consisting of carbon and hydrogen, R-S-(CR-R).Y for example, methyl, ethyl, propyl, isopropyl, 1-butyl, 2-bu tyl, isobutyl, tert-butyl, pentyl, 2-methylbutyl, 1,1-dimethyl (Ia) propyl, hexyl, heptyl, octyl, nonyl, and decyl. 55 "halo' means fluoro, chloro, bromo, and iodo. In step a of Scheme A, sulfide of formula (A) is oxidized “haloalkyl means an alkyl further consisting of, from one with meta-chloroperoxybenzoic acid (mCPBA) in a polar to the maximum possible number of identical or different, solvent below 0°C. to provide sulfoxide of formula (B). In halos, for example, fluoromethyl, difluoromethyl, trifluorom most cases, dichloromethane is the preferred solvent for oxi ethyl, 1-fluoromethyl 2-fluoroethyl, 2.2.2-trifluoroethyl, 60 dation. chloromethyl, trichloromethyl, and 1.1.2.2-tetrafluoroethyl. In step b of Scheme A, sulfoxide (B) is iminated with Sodium azide in the presence of concentrated Sulfuric acid in an aprotic solvent under heating to provide Sulfoximine of DETAILED DESCRIPTION OF THE INVENTION formula (C). In most cases, chloroform is the preferred sol 65 vent for this reaction. Compounds of the following formula are synergistic with a In step c of Scheme A, the nitrogen of Sulfoximine (C) can variety of other pesticides. be either cyanated with cyanogen bromide in the presence of US 8,349,815 B2 3 4 a base, or nitrated with nitric acid in the presence of acetic anhydride under mildly elevated temperature, or carboxy Scheme C lated with alkyl (R) chloroformate in the presence of base such as 4-dimethylaminopyridine (DMAP) to provide N-sub N1 X N1 X stituted sulfoximine (Ia). Base is required for efficient cyana KHMDS tion and carboxylation and the preferred base is DMAP. RZ. whereas sulfuric acid is used as catalyst for efficient nitration R1 R R5 reaction. (Ia) (Ib) The compounds of formula (Ia), wherein X represents. CN 10 and R. R. R. R. and Y are as previously defined, can be The starting sulfides (A) in Scheme A can be prepared in prepared by the mild and efficient method illustrated in different ways as illustrated in Schemes D, E, FG, H, and I. Scheme B. In Scheme D, the sulfide of formula (A), wherein R', R 15 and Y are as previously defined, n=1, and R=H, can be Scheme B prepared from the chloride of formula (D) by nucleophilic substitution with the sodium salt of an alkylthiol. S-L-(CRR)-Y 8. > PhI(OAc)2, NH2CN RI Scheme D (A) R2 R2 Y --> Y RSNa CN C R-S N1 25 | b (D) (A1) S-L-(CRR)-Y - > mCPBA, K2CO3 R1 O In Scheme E, the sulfide of formula (A), wherein R', R (F) RuCl3, NaIO4 and Y are as previously defined, n=3, and R=H, can be 30 prepared from the chloride of formula (D) by reacting with a 2-mono substituted methyl malonate in the presence of base CN such as potassium tert-butoxide to provide 2,2-disubstituted N1 malonate, hydrolysis under basic conditions to form a diacid, 35 decarboxylation of the diacid by heating to give a monoacid, reduction of the monoacid with borane-tetrahydrofuran com plex to provide an alcohol, tosylation of the alcohol with toluenesulfonyl chloride (tosyl chloride) in the presence of a base like pyridine to give a tosylate and replacement of the In stepa of Scheme B, sulfide is oxidized withiodobenzene 40 tosylate with the sodium salt of the desired thiol. diacetate in the presence of cyanamide at 0°C. to give sulfil imine (F). The reaction can be carried out in a polar aprotic solvent like dichloromethane. Scheme E 45 Y In step b of Scheme B, the sulfillimine (F) is oxidized with CCH-Y - MeOC - e mCPBA. A base such as potassium carbonate is employed to 2 KOtBu LiOH neutralize the acidity of mCPBA. Protic polar solvents such (D-2) RCH(COMe), MeOC R2 as ethanol and water are used to increase the solubility of the Sulfillimine starting material and the base employed. The Sul 50 HOC Y Y BH THF filimine (F) can also be oxidized with aqueous Sodium or HOC potassium periodinate Solution in the presence of catalyst HOC 2 ruthenium trichloride hydrate or similar catalyst. The organic Solvent for this catalysis can be polar aprotic solvent Such as 55 HO Y --> TSO Y > dichloromethane, chloroform, or acetonitrile. \ { TsCI, Py \ { NaSR The C-carbon of the N-substituted sulfoximine of formula R2 R2 (Ia), i.e., n=1, R=H in the (CRR) group adjacent to the N-substituted sulfoximine function can be further alkylated or halogenated (R) in the presence of a base such as potas 60 sium hexamethyldisilamide (KHMDS) to give N-substituted R-S\ (' sulfoximines of formula (Ib), wherein R. R. R. R. X., L and Y are as previously defined and Z is an appropriate leav (A2) ing group, as illustrated in Scheme C. The preferred leaving 65 groups are iodide (R-alkyl), benzenesulfonimide (R—F), In Scheme F, the sulfide of formula (As), wherein R', R tetrachloroethene (R—C1, and tetrafluoroethene (R—Br). and Y are as previously defined, n=2, and R=H, can be US 8,349,815 B2 5 6 prepared from the nitrile of formula (E) by deprotonation In Scheme G, the sulfide of formula (A), wherein R', S with a strong base and alkylation with an alkyl iodide to give and L taken together form a ring, n=0, and Y isopropyl or O-alkylated nitrile, hydrolysis of the O-alkylated nitrile in the phenyl can be prepared from the unsubstituted cyclic sulfide presence of a strong acid like HCl to give an acid, reduction of 5 wherein m=0, 1. Chlorination of the cyclic sulfide starting the acid with borane-tetrahydrofuran complex to provide an material with N-chlorosuccinimide in benzene followed by alcohol, tosylation of the alcohol with tosyl chloride in the alkylation with Grignard reagent can lead to the desired Sul presence of a base like pyridine to give a tosylate and replace fide (A) in Satisfactory yield. ment of the tosylate with the sodium salt of the desired thiol. 10

Scheme F Scheme G - Ri A M Y base HCI 15 iii. iii. i iii. NC R2I Y - Y - -e- NC NCS, YMgCl (E) S S C S Y (A4) 2O R2 R2 ) Y BH THF HerTsCI, Py An alternative method for the preparation of sulfides of HOC HO formula (A), wherein R', Sand L taken together form a ring, * n=0, m=0, and Y-6-halo, 6-(C-C.)alkyl, 6-(C-C,) R2 R2 haloalkyl or 6-(C-C)alkoxy substituted 3-pyridyl is high lighted in Scheme H. Accordingly, the corresponding appro Y NaSR - Y priately substituted chloromethylpyridine- is treated with thio TSO s 30 urea, hydrolyzed and subsequently alkylated with 1-bromo RI 3-chloropropane under aqueous base conditions, and (A3) cyclized- in the presence of a base like potassium tert-butoxide in a polar aprotic solvent such as tetrahydrofuran (THF).

Scheme H NH thiourea N S 1. 1-bromo-3-chloropropane N C --- -e- EtOH, 259 C. Or * NaOH, H.O. 10 c. 2 2 Sub N Sub N

2 Sub N

KOBu THF, HMPA, 259 C. 2 N sub (A4) US 8,349,815 B2 7 8 In Scheme I, the sulfide of formula (As), wherein R' is haloalkoxypyridin-3-yl have been disclosed in US Patent previously defined, L is a bond, n=0 and Y is 6-chloropyridin- Publication 20050228027, whose teachings are incorporated 3-yl can be prepared from 2-chloro-5-bromopyridine with a herein. halo-metal exchange followed by a substitution with disul fide. 5 EXAMPLES The examples are for illustration purposes and are not to be construed as limiting the invention disclosed in this document Scheme I to only the embodiments disclosed in these examples. BuLi N Br Russi N n 10 Example I (6-Trifluoromethylpyridin-3-yl)methyl(methyl)- C 4. C 4. oxido-'-sulfanylidenecyanamide (1) (A5) (1) 15 N s1 Sulfoximine compounds of type Ib wherein R', S and L / \ taken together form a saturated 5- or 6-membered ring and FC % n=1 can be prepared by the methods illustrated in Scheme J 3 CN wherein X and Y are as previously defined and m is 0 or 1.

Scheme J

c i C -- -- Y S NaN, H2SO4 S BrCN, DMAP S Base S or MSH MV or HNO3/Ac2O WW Y-CH2C1,-78° C. MV O O NH or CICOMe, DMAP O N X O N-X Ib

C

c Y N Clu Y -> CluS 21 S / YHM O

In step a of Scheme J, which is similar to stepb of Scheme (6-Trifluoromethylpyridin-3-yl)methyl(methyl)-oxido A, sulfoxide is iminated with sodium azide in the presence of " -sulfanylidenecyanamide (1) was prepared from 3-chlo concentrated sulfuric acid or with O-mesitylsulfonylhy- romethyl-6-(trifluoromethyl)pyridine according to the fol droxylamine in a polar aprotic Solvent to provide Sulfox- lowing three step sequence: imine. Chloroform or dichloromethane are the preferred sol VentS. In step b of Scheme J, similar to step c of Scheme A, the 45 nitrogen of sulfoximine can be either cyanated with cyanogen N NaSCH (A) bromide, or nitrated with nitric acid followed by treatment C EcoHo, so c. with acetic anhydride under refluxing conditions, or carboxy- (67%) lated with methyl chloroformate in the presence of base such FC 4. as DMAP to provide N-substituted cyclic sulfoximine. Base 50 -CH3 is required for efficient cyanation and carboxylation and the N S preferred base is DMAP, whereas sulfuric acid is used as catalyst for efficient nitration reaction. FC % In step c of Scheme J, the C-carbon of N-substituted sul- (A) foximine can be alkylated with a heteroaromatic methyl 55 halide in the presence of a base such as KHMDS or butyl lithium (Bulli) to give the desired N-substituted sulfox- To a solution of 3-chloromethyl-6-(trifluoromethyl)pyri imines. The preferred halide can be bromide, chloride or dine (5.1 g, 26 mmol) in dimethylsulfoxide (DMSO; 20 mL) iodide. was added in one portion Sodium thiomethoxide (1.8 g. 26 Alternatively, the compounds of formula (Ib) can be pre- 60 mmol). A violent exothermic reaction was observed which pared by a first C.-alkylation of sulfoxides to give C-substi- resulted in the reaction turning dark. The reaction was stirred tuted sulfoxides and then an imination of the sulfoxide fol- for 1 hr., then additional sodium thiomethoxide (0.91 g, 13 lowed by N-substitution of the resulting sulfoximine by using mmol) was added slowly. The reaction was stirred overnight, the steps c, a and b respectively as described above for after which it was poured into H2O and several drops of conc. Scheme J. 65 HCl were added. The mixture was extracted with EtO (3x50 Compounds in which Y represents claimed substituents mL) and the organic layers combined, washed with brine, other than 6-(C-C) haloalkylpyridin-3-yl and 6-(C-C) dried over MgSO and concentrated. The crude product was US 8,349,815 B2 10 purified by chromatography (Prep 500, 10% acetone/hex acetone/hexanes) to furnish the sulfoximine (1) as an off anes) to furnish the sulfide (A) as a pale yellow oil (3.6 g. white solid (0.28 g., 44%). Mp=135-137° C.; H NMR (300 67%). "H NMR (300 MHz, CDC1): 88.6 (s, 1H), 7.9 (d. 1H), MHz, CDC1): 88.8 (s, 1H), 8.1 (d. 1H), 7.8 (d. 1H), 4.7 (m, 7.7 (d. 1H), 3.7 (s. 2H), 2.0 (s, 3H); GC-MS: mass calcd for 2H), 3.2 (s, 3H); LC-MS (ELSD): mass calcd for CHFNSIM 207. Found 207. 5 CHFNOS M+H" 264.04. Found 263.92.

(B) Example II

c.,3 -e-H2NCN, Phi(OAc)2 N s1 CH2Cl2, 0°C. 10 (14%) 1-(6-Trifluoromethylpyridin-3-yl)ethyl(methyl)- 2 oxido-'-sulfanylidenecyanamide (2) FC N (A) 15 N s1 CH3 2 N N sa FC N NON a'sS. 2 (B) FC N CN To a solution of sulfide (A)(3.5g, 17 mmol) and cyanamide (2) (1.4 mg., 34 mmol) in dichloromethane (30 mL) at 0°C. was (A) added iodobenzenediacetate (11.0 g, 34 mmol) all at once. 25 CH The reaction was stirred for 30 minutes then allowed to warm N s1 1. KHMDS, HMPA, A \ THF, -78° C. to room temperature overnight. The mixture was diluted with 2 O N-CN-Ho 2. CHI dichloromethane (50 mL) and washed with HO. The aque FC N ous layer was extracted with ethyl acetate (4x50 mL), and the (59%) combined dichloromethane and ethyl acetate layers dried 30 (1) over MgSO and concentrated. The crude product was tritu CH3 rated with hexanes and purified by chromatography (chroma N s1 CH totron, 60% acetone/hexanes) to furnish the sulfillimine (B) as M \, a yellow gum (0.60g, 14%). IR (film)3008,2924, 2143, 1693 35 2 O N-CN cm': "H NMR (300 MHz, CDC1): 88.8 (s, 1H),8.0 (d. 1H), FC N 7.8 (d. 1H), 4.5 (d. 1H), 4.3 (d. 1H), 2.9 (s.3H); LC-MS (ESI): mass calcd for CHFNS M+H 248.04. Found 248. (2) 40 1-(6-Trifluoromethylpyridin-3-yl)ethyl(methyl)-oxido (C) -sulfanylidenecyanamide (2) was prepared from [(6-trif c.3 -e-mCPBA. K2CO3 N s1' EcoH.H.O. oec. luoromethylpyridin-3-yl)methyl-(methyl)-oxido- '-sulfa (44%) nylidenecyanamide (1) using the method outlined in Scheme 2 N FC N NON 45 C: To a solution of sulfoximine (1) (50 mg, 0.19 mmol) and (B) hexamethyl-phosphoramide (HMPA; 17 uL, 0.10 mmol) in N s1 CH A \ tetrahydrofuran (THF: 2 mL) at -78°C. was added potassium - O N-CN 50 hexamethyldisilazane (KHMDS: 0.5 M in toluene, 420 uL. FC N 0.21 mmol) dropwise. The solution was stirred at -78°C. for (1) an additional 20 min, after which iodomethane (13 uL, 0.21 mmol) was added. The reaction was allowed to warm to room To a solution of m-chloroperbenzoic acid (mCPBA: 80%, 55 temperature over the course of 1 hr., after which it was 1.0 g, 4.9 mmol) in EtOH (10 mL) at 0°C. was added a quenched with Saturated aqueous (aq.) NHCl and extracted solution of KCO (1.4g, 10 mmol) in HO (7 mL). The with dichloromethane. The organic layer was dried over solution was stirred for 20 min and then a solution of sulfil NaSO concentrated, and the crude product purified by imine (B) (0.60g, 2.4 mmol) in EtOH (20 mL) was added all chromatography (chromatotron, 70% acetone/CHCl) to at once. The reaction was stirred at 0°C. for 30 min, and then 60 furnish the sulfoximine (2) as a 2:1 mixture of diastereomers allowed to warm to room temperature over the course of 1 hr. (colorless oil; 31 mg, 59%). "H NMR (300 MHz, CDC1): 8 The reaction was quenched with aq. Sodium bisulfate and the (major diastereomer) 8.8 (s, 1H), 8.1 (d. 1H), 7.8 (d. 1H), 4.6 mixture concentrated to remove ethanol. The resulting mix (q, 1H), 3.0 (s.3H), 2.0 (d. 3H); (minor diastereomer) 8.8 (s. ture was extracted with dichloromethane and the combined 65 1H), 8.1 (d. 1H), 7.8 (d. 1H), 4.6 (q, 1H), 3.1 (s.3H), 2.0 (d. organic layers dried over MgSO and concentrated. The crude 3H); LC-MS (ELSD): mass calcd for CHFNOS product was purified by chromatography (chromatotron, 50% M+H" 278.06. Found 278.05. US 8,349,815 B2 11 12 Example III then cooledbackdownto 10°C. Additional 10 NNaOH (0.68 mL, 6.8 mmol) was added, followed by 1-bromo-3-chloro 2-(6-Trifluoromethylpyridin-3-yl)-1-oxido-tetrahy propane (0.67 mL, 6.8 mmol) all at once. The reaction was dro-1H-1'-thien-1-ylidenecyanamide (3) stirred at room temperature overnight, then extracted with dichloromethane. The combined organic layers were washed with brine, dried over NaSO and concentrated to furnish the sulfide (B) as a colorless oil (1.7 g.96%). No further attempt (3) was made to purify the product. "H NMR (300 MHz, CDC1): 10 & 8.6 (s, 1H), 7.8 (d. 1H), 7.6 (d. 1H), 3.8 (s. 2H), 3.6 (t, 2H), N S M \, 2.6 (t, 2H), 2.0 (quint, 2H). 2 O N FC N CN (C) 15

- KOBu- -e- 2-(6-Trifluoromethylpyridin-3-yl)-1-oxido-tetrahydro THF, HMPA, 259 C. 1H-1'-thien-1-ylidene-cyanamide (3) was prepared from 2 (15%) 3-chloromethyl-6-(trifluoromethyl)-pyridine according to FC N the 5 step sequence outline below: (B)

(A) thiourea C -> EtOH, 259 C. 25 (58%)

NH To a Suspension of potassium tert-butoxide (1.5 g., 13 N-s-s NH, HCI 30 mmol) in THF (12 mL) was added HMPA (1.7 mL, 10 mmol) followed by a solution of sulfide (B) (1.8 g. 6.7 mmol) in THF (3 mL) dropwise. The reaction was allowed to stir at room temperature overnight, followed by concentration and purifi cation by chromatography (Biotage, 40% EtOAc/hexanes) to 35 To a suspension of thiourea (1.2g, 16 mmol) in EtOH (25 furnish cyclized product (C) as an orange oil (230 mg, 15%). mL) was added a solution of 3-chloromethyl-6-(trifluorom "H NMR (300 MHz, CDC1): 88.7 (s, 1H),8.0 (d. 1H), 7.6 (d. ethyl)pyridine in EtOH (10 mL). The suspension was stirred 1H), 4.6 (dd. 1H), 3.2 (m, 1H), 3.1 (m, 1H), 2.5 (m, 1H), 2.3 at room temperature for 2 days, during which a white precipi (m. 1H), 2.1-1.9 (m. 2H). tated formed. The precipitate was filtered to give the desired 40 amidine hydrochloride as a white solid (2.4 g 58%). (D) Mp=186-188° C. No further attempt was made to purify the H2NCN, PhI(OAc) product. H NMR (300 MHz, CDC1): 88.9 (bs, 4H), 8.4 (s, He N S CHCl2, 0°C. 1H), 7.6 (d. 1H), 7.3 (d. 1H), 4.2 (s. 2H); LC-MS (ELSD): 45 (56%) mass calcd for C.H.FNS M+H" 236.05. Found 236.01. 2 FC N

(C) (B) NH 50 N S ls NH2 1-bromo-3-chloropropane NaOH, H2O, 10° C. 2 (96%) FC N 55 (D) (A) To a solution of sulfide (C) (230 mg. 0.99 mmol) and cyanamide (83 mg, mmol) in dichloromethane (5 mL) at 0°C. was added iodobenzenediacetate (350 mg, 1.1 mmol) all at FC Crs4. 60 once. The reaction was stirred for 3 hr, then concentrated and (B) the crude product purified by chromatography (chroma totron, 50% acetone/hexanes) to furnish the sulfillimine (D) as To a solution of amidine hydrochloride (A) (1.8 g. 6.8 an orange oil (150 mg, mixture of diastereomers, 56%). "H mmol) in HO (12 mL) at 10°C. was added 10N NaOH (0.68 65 NMR (300 MHz, CDC1): 8 8.8 (s, 1H), 7.9 (d. 1H), 7.8 (d. mL, 6.8 mmol), which resulted in the formation of a white 1H), 4.8 (dd. 1H), 3.5 (m, 2H), 2.9-2.7 (m, 2H), 2.6 (m. 1H), precipitate. The suspension was heated at 100° C. for 30 min, 2.3 (m. 1H). US 8,349,815 B2 13 14 off-white solid; mp=155-164° C. LC-MS (ELSD): mass

(E) calcd for CHCINOS M-H 242. Found 242. The diaste reomers of (5) could be separated by recrystallization (2:1 MeOH/HO) and subsequent chromatotron chromatography of the supernate to provide (6) and (7) (Stereochemistry arbi trarily assigned). (6) mCPBA, K2CO EtOH/HO, 0° C.

(44%) N s1 10 MV 2 O N C N N-CN CN (7) (3) 15 N s1 To a solution of mCPBA (80%, 180 mg. 0.82 mmol) in MV EtOH (3 mL) at 0°C. was added a solution of KCO (230 2 O N mg, 1.7 mmol) in HO (1.5 mL). The solution was stirred for C N 20 min and then a solution of sulfillimine (D) (150 mg, 0.55 CN 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 Compound (6) was isolated as a white solid; mp=163-165° decanted into a separate flaskand concentrated to give a white C.; H NMR (300 MHz, CDC1): 88.4 (d. 1H), 7.9 (dd. 1H), solid. The solid was slurried in CHCl, filtered, and concen 7.5 (d. 1H), 4.6 (q, 1H), 3.1 (s, 3H), 2.0 (d. 3H); LC-MS trated to furnish pure sulfoximine (3) as a colorless oil (72 mg, 25 (ELSD): mass calcd for CHCINOS M+H", 244. Found 44%). "H NMR (300 MHz, CDC1): 8 (1.5:1 mixture of 244. diastereomers) 8.8 (s. 2H), 8.0 (d. 2H), 7.8 (d. 2H), 4.7 (d. Compound (7) was isolated as a colorless oil; H NMR 1H), 4.6 (q, 1H), 4.0-3.4 (m, s, 4H), 3.0-2.4 (m, 8H); LC-MS (300 MHz, CDC1,) 88.4 (d. 1H), 7.9 (dd. 1H), 7.5 (d. 1H), 4.6 (ELSD): mass calcd for CHFNOS M+H" 290.06. (q, 1H), 3.0 (s.3H), 2.0 (d. 3H); LC-MS (ELSD): mass calcd Found 289.99. 30 for CHCINOS M+H", 244. Found 244. Example IV Example VI (6-Chloropyridin-3-yl)methyl(methyl)oxido- - Sulfanylidenecyanamide (4) 35 2-(6-Chloropyridin-3-yl)-1-oxido-tetrahydro-1H (4) 1'-thien-1-ylidenecyanamide (8) N s1 MV e O N - CN C N 40 (8)

(6-Chloropyridin-3-yl)methyl(methyl)oxido-N-sulfa N S nylidenecyanamide (4) was prepared from 3-chloromethyl M \, 6-chloropyridine via the same 3 step sequence outline in 2 O Example I. Product was a white solid; mp=115-117° C.; H 45 C N NMR (300 MHz, CDOD/CDC1) 88.5 (d. 1H), 8.0 (dd. 1H), CN 7.6 (d. 1H), 5.0 (s. 2H), 3.4 (s, 3H); LC-MS (ELSD): mass calcd for CHCINOS M+H" 230. Found 230. 2-(6-Chloropyridin-3-yl)-1-oxido-tetrahydro-1H-1'- thien-1-ylidenecyanamide (8) was prepared from 3-chlorom Example V 50 ethyl-6-chloropyridine according to the same five step sequence described in Example III. Product was a colorless 1-(6-Chloropyridin-3-yl)ethyl(methyl)oxido- - gum and a 1:1 ratio of diastereomers. Diastereomer 1: IR Sulfanylidenecyanamide (5) (film) 3439, 3006, 2949, 21.94 cm; H NMR (300 MHz, (5) CDC1): 88.4 (d. 1H), 7.8 (dd. 1H), 7.4 (d. 1H), 4.6 (dd. 1H), 55 3.6 (m. 2H), 2.4-2.7 (m, 4H); GC-MS: mass calcd for CHCINOS M+H"256. Found 256. Diastereomer 2: IR N s1 (film) 3040,2926, 2191 cm; H NMR (300 MHz, CDC1): MV 88.4 (d. 1H), 7.8 (dd. 1H), 7.4 (d. 1H), 4.7 (dd. 1H), 3.8 (ddd, 2 O N C N 60 1H), 3.4 (m. 1H), 2.8 (m. 1H), 2.6 (m. 2H), 2.3 (m. 1H): CN GC-MS: mass calcd for CHCINOSM+H" 256. Found 256. 1-(6-Chloropyridin-3-yl)ethyl(methyl)oxido- '-sulfa Insecticidal Test on Green Peach Aphid (Myzus persicae) nylidenecyanamide (5) was prepared from (6-chloropyridin Using Mixtures of Sulfoximines and Selected Pesticides 3-yl)methyl(methyl)oxido-'-sulfanylidenecyanamide (4) 65 Dose-response, foliar spray assays were designed and con via the same protocol as described in Example II. The final ducted to evaluate synergic effects of mixtures between the product, isolated as a 3:2 mixture of diastereomers, was an following compounds US 8,349,815 B2 15 16 chemical application. Four seedlings were used for each treat Compound 1 ment. A hand-held Devilbiss sprayer was used for spraying a solution to both sides of cabbage leaves until runoff. Refer N S 1. ence plants (solvent check) were sprayed with the diluent MV only. Treated plants were held in a holding room for three 2 O N-CN days at approximately 23° C. and 40% RH prior to grading. C N Evaluation was conducted by counting the number of live Compound 2 aphids perplant under a microscope. Insecticidal activity was

10 measured by using Abbott’s correction formula: Corrected% N s1 Control=100*(X-Y)/X where X=No. of live aphids on sol M \, vent check plants Y-No. of live aphids on treated plants. 2 O N-CN CF N TABLE 1

15 Results spinosad, spinetoram, gamma-cyhalothrin, methoxy fenozide, or chlorpyrifos, on green peach aphid. % Control of green peach Assay 1: Master solutions at 1000 ppm were made by Test conc, aphid dissolving technical materials in acetone:MeOH (1:1) at 1 Com- Com- PDIIl Predicted from mg/ml. For a mixture between two test compounds, 0.047 ml of the master Solution from each component were combined pound pound Com Com Measured Colby and diluted 32x with the acetone:MeOH solvent (0.094 ml of A. B A. B combination calculation combination+2.906 ml solvents, resulting in 15.6 ppm for Spinosad O.O12 O.O12 35.7 O.OO each ai) and then 5x with 0.025% Tween 20 in H2O (12 ml) Spinosad O.78 O.78 37.5 O.OO 25 Spinosad O.20 O.20 40.2 O.OO to obtain a 3.125 ppm solution. For non-mixtures, the master Spinosad O.78 O.78 69.64 49.6 solutions were diluted 64x with acetone:MeOH (0.047 Spinosad 3.13 3.13 93.8 76.8 ml+2.953 ml solvent, resulting in 15.6 ppm) and then 5x with Spinetoram O.O12 O.O12 25.5 O.OO 0.025% Tween 20 in H2O (12 ml) to obtain a 3.125 ppm Spinetoram O.78 O.78 32.14 O.OO Spinetoram O.20 O.20 33.9 O.OO solution. For both Mixture and non-mixture, lower concen Spinetoram O.78 O.78 692 64.7 trations (0.78, 0.195, 0.049 and 0.012 ppm) were prepared by 30 gamma- O.195 O.195 SO.OO O.OO sequentially diluting 4 ml of the higher concentration (start cyhalothrin ing from 3.125 ppm) with 12 ml of a diluent consisting 80 gamma- 0.78 0.78 83.04 79.2 cyhalothrin parts of 0.025% Tween 20 in H2O and 20 parts of acetone: Methoxyfenozide 3.13 3.13 1OOOO 75.89 MeOH Chlorpyrifos O.78 O.78 73.66 49.SS Assay 2: Master solutions at 1000 ppm were made by 35 Chlorpyrifos 3.13 3.13 94.64 75.89 dissolving technical materials in acetone:MeOH (1:1) at 1 2 Spinosad O.20 O.20 85.91 69.55 2 Spinosad O.78 O.78 1OOOO 98.18 mg/ml. For mixtures between Comp 2 and Comp 3, 4 or 5, 2 Spinetoram O.20 O.20 76.36 69.55 0.047 ml of the master solution from each component were 2 gamma- O.78 O.78 1OOOO 99.77 combined and diluted 32x with acetone:MeOH (0.094 ml of cyhalothrin combination+2.906 ml, resulting in 15.6 ppm for eachai) and 40 2 Methoxyfenozide 0.05 O.78 43.18 O.OO then 5x with 0.025% Tween 20 in H2O (12 ml) to obtain a 2 Methoxyfenozide 0.20 3.13 76.36 69.55 3.125 ppm solution. For mixtures between Comp 2 and Comp *Colby Formula = 100-((100-% control of compoundA)x (100-% control of compound 6 or 7, 0.047 ml of the master solution from Comp 2 and 0.752 2)), 100 (Colby, S.R. 1967. Calculating synergistic and antagonistic responses of herbicide ml of the master solution from Comp 6 or 7 were combined combinations. Weeds 15:20-22) and diluted 3.755x with acetone:MeOH (0.799 ml of combi 45 nation+2.201 ml solvent, resulting in 15.6 ppm for Comp 2 Acid & Salt Derivatives, and Solvates and 250 ppm for Comp 6 or 7) and then 5x with 0.025% Tween 20 inH2O (12 ml) to obtain a 3.125 ppm solution for The compounds disclosed in this invention can be in the Comp 2 and a 50 ppm solution for Comp 6 or 7. For non form of pesticidally acceptable acid addition salts. mixtures with Comp 2, 3, 4 or 5, the master solutions were 50 By way of non-limiting example, an amine function can diluted 64x with acetone:MeOH (0.047 ml+2.953 ml solvent, form salts with hydrochloric, hydrobromic, sulfuric, phos resulting in 15.6 ppm) and then 5x with 0.025% Tween 20 in phoric, acetic, benzoic, citric, malonic, Salicylic, malic, H2O (12 ml) to obtain a 3.125 ppm solution. For non-mix fumaric, oxalic, succinic, tartaric, lactic, gluconic, ascorbic, tures with Comp 6 or 7, the master solutions were diluted maleic, aspartic, benzenesulfonic, methanesulfonic, ethane 3.989x with acetone:MeOH (0.752 ml+2.248 ml solvent, 55 Sulfonic, hydroxymethanesulfonic, and hydroxyethane resulting in 250 ppm) and then 5x with 0.025% Tween 20 in Sulfonic, acids. H2O (12 ml) to obtain a 50 ppm solution. For both Mixture Additionally, by way of non-limiting example, an acid and non-mixture, lower concentrations (0.78, 0.195, 0.049 function can form salts including those derived from alkali or and 0.012 ppm for Comp 2, 3, 4 and 5; 12.5, 3.125, 0.78 and alkaline earth metals and those derived from ammonia and 0.195 for Comp 6 and 7) were prepared by sequentially dilut 60 amines. Examples of preferred cations include Sodium, potas ing 4 ml of the higher rate (starting from 3.125 or 50 ppm) sium, magnesium, and aminium cations. with 12 ml of a diluent consisting 80 parts of 0.025% Tween The salts are prepared by contacting the free base form with 20 in H2O and 20 parts of acetone:MeOH (1:1). a sufficient amount of the desired acid to produce a salt. The For both Assays 1 and 2, cabbage seedlings grown in 3-inch free base forms may be regenerated by treating the salt with a pots, with 2-3 small (3-5 cm) true leaves, were used as test 65 Suitable dilute aqueous base solution Such as dilute aqueous substrate. The seedlings were infested with 20-50 green NaOH, potassium carbonate, ammonia, and sodium bicar peach aphids (wingless adult and nymph) 1 day prior to bonate. US 8,349,815 B2 17 18 As an example, in many cases, a pesticide is modified to a pod weevil), Ceutorhynchus napi (cabbage curculio), more water Soluble form e.g. 2,4-dichlorophenoxyacetic acid Chaetocnema spp. (chrysomelids), Colaspis spp. (soil dimethyl amine salt is a more water soluble form of 2,4- beetles), Conoderus scalaris, Conoderus stigmosus, dichlorophenoxyacetic acid a well known herbicide. Conotrachelus menuphar (plum curculio), Cotinus initidis The compounds disclosed in this invention can also form (Green June beetle), Crioceris asparagi (asparagus beetle), stable complexes with solvent molecules that remain intact Cryptolestes ferrugineus (rusty grain beetle), Cryptolestes after the non-complexed solvent molecules are removed from pusillus (flat grain beetle), Cryptolestes turcicus (Turkish the compounds. These complexes are often referred to as grain beetle), Ctenicera spp. (wireworms), Curculio spp. “Solvates. (weevils), Cyclocephala spp. (grubs), Cylindrocpturus 10 adspersus (Sunflower stem weevil), Deporaus marginiatus Stereoisomers (mango leaf-cutting weevil), Dermestes lardarius (larder beetle), Dermestes maculates (hide beetle), Diabrotica spp. Certain compounds disclosed in this invention can exist as (chrysolemids), Epilachna varivestis (Mexican bean beetle), one or more Stereoisomers. The various stereoisomers Faustinus cubae, Hylobius pales (pales weevil), Hypera spp. include geometric isomers, diastereomers, and enantiomers. 15 (weevils), Hypera postica (alfalfa weevil), Hyperdoes spp. Thus, the compounds disclosed in this invention include race (Hyperodes weevil), Hypothenemus hampei (coffee berry mic mixtures, individual stereoisomers, and optically active beetle), Ips spp. (engravers), Lasioderma serricorne (ciga mixtures. rette beetle), Leptinotarsa decemlineata (Colorado potato It will be appreciated by those skilled in the art that one beetle), Liogeny's fiscus, Liogenys suturalis, Lissorhoptrus stereoisomer may be more active than the others. Individual Oryzophilus (rice water weevil), Lyctus spp. (wood beetles/ Stereoisomers and optically active mixtures may be obtained powder post beetles), Maecolaspis joliveti, Megascelis spp., by selective synthetic procedures, by conventional synthetic Melanotus communis, Melligethes spp., Melligethes aeneus procedures using resolved starting materials, or by conven (blossom beetle), Melolontha melolontha (common Euro tional resolution procedures. pean cockchafer), Oberea brevis, Oberea linearis, Oryctes 25 rhinoceros (date palm beetle), Oryzaephilus mercator (mer Pests chant grain beetle), Oryzaephilus Surinamensis (sawtoothed grain beetle), Otiorhynchus spp. (weevils), Oulema melano In another embodiment, the invention disclosed in this pus (cereal leaf beetle), Oulema Oryzae, Pantomorus spp. document can be used to control pests. (weevils), Phyllophaga spp. (May/June beetle), Phyllophaga In another embodiment, the invention disclosed in this 30 cuyabana, Phyllotreta spp. (chrysomelids), Phynchites spp., document can be used to control pests of the Phylum Nema Popillia japonica (Japanese beetle), Prostephanus truncates toda. (larger grain borer), Rhizopertha dominica (lesser grain In another embodiment, the invention disclosed in this borer), Rhizotrogus spp. (Eurpoean chafer), Rhynchophorus document can be used to control pests of the Phylum Arthro spp. (weevils), Scolytus spp. (wood beetles). Shenophorus poda. 35 spp. (Billbug), Sitona lineatus (pea leaf weevil), Sitophilus In another embodiment, the invention disclosed in this spp. (grain weevils), Sitophilus granaries (granary weevil), document can be used to control pests of the Subphylum Sitophilus Oryzae (rice weevil), Stegobium paniceum (drug Chelicerata. store beetle), Tribolium spp. (flour beetles), Tribolium casta In another embodiment, the invention disclosed in this neum (red flour beetle), Tribolium confilsum (confused flour document can be used to control pests of the Class Arachnida. 40 beetle), Trogoderma variabile (warehouse beetle), and In another embodiment, the invention disclosed in this Zabrus tenebioides. document can be used to control pests of the Subphylum In another embodiment, the invention disclosed in this Myriapoda. document can be used to control Dermaptera (earwigs). In another embodiment, the invention disclosed in this In another embodiment, the invention disclosed in this document can be used to control pests of the Class Symphyla. 45 document can be used to control Dictyoptera (cockroaches). In another embodiment, the invention disclosed in this A non-exhaustive list of these pests includes, but is not lim document can be used to control pests of the Subphylum ited to, Blattella germanica (German cockroach), Blatta ori Hexapoda. entalis (oriental cockroach), Parcoblatta pennylvanica, In another embodiment, the invention disclosed in this Periplaneta americana (American cockroach), Periplaneta document can be used to control pests of the Class Insecta. 50 australoasiae (Australian cockroach), Periplaneta brunnea In another embodiment, the invention disclosed in this (brown cockroach), Periplaneta fuliginosa (Smokybrown document can be used to control Coleoptera (beetles). A cockroach), Pyncoselus Suninamensis (Surinam cockroach), non-exhaustive list of these pests includes, but is not limited and Supella longipalpa (brownbanded cockroach). to, Acanthoscelides spp. (weevils), Acanthoscelides Obtectus In another embodiment, the invention disclosed in this (common bean weevil), Agrilus planipennis (emerald ash 55 document can be used to control Diptera (true flies). A non borer), Agriotes spp. (wireworms). Anoplophora glabripen exhaustive list of these pests includes, but is not limited to, nis (Asian longhorned beetle), Anthonomus spp. (weevils), Aedes spp. (mosquitoes), Agromyza frontella (alfalfa blotch Anthonomus grandis (boll weevil), Aphidius spp., Apion spp. leafminer), Agromyza spp. (leafminer flies), Anastrepha spp. (weevils), Apogonia spp. (grubs), Ataenius spretulus (Black (fruit flies), Anastrepha suspensa (Caribbean fruit fly), Turgrass Ataenius), Atomaria linearis (pygmy mangold 60 Anopheles spp. (mosquitoes), Batrocera spp. (fruit flies), beetle), Aulacophore spp., Bothy noderes punctiventris (beet Bactrocera cucurbitae (melon fly), Bactrocera dorsalis (ori root weevil), Bruchus spp. (weevils), Bruchus pisorum (pea ental fruit fly), Ceratitis spp. (fruit flies), Ceratitis capitata weevil), Cacoesia spp., Callosobruchus maculatus (Southern (Mediterranea fruit fly), Chrysops spp. (deer flies), cowpea weevil), Carpophilus hemipteras (dried fruit beetle), Cochliomyia spp. (screwworms), Contarinia spp. (Gall Cassida vittata, Cerosterna spp., Cerotoma spp. (chry 65 midges), Culex spp. (mosquitoes), Dasineura spp. (gall Someids), Cerotoma trifurcata (bean leaf beetle), Ceutorhyn midges), Dasineura brassicae (cabbage gall midge), Delia chus spp. (weevils), Ceutorhynchus assimilis (cabbage seed spp., Delia platura (seedcorn maggot), Drosophila spp. (vin US 8,349,815 B2 19 20 egar flies), Fannia spp. (filth flies), Fannia canicularis (little raspidiotus perniciosus (San Jose scale), Rhapalosiphun house fly), Fannia scalaris (latrine fly), Gasterophilus intes spp. (aphids), Rhapalosiphum maida (corn leaf aphid), tinalis (horse botfly), Gracillia perseae, Haematobia irritans Rhapalosiphum padi (oat bird-cherry aphid), Saissetia spp. (horn fly), Hvlemyia spp. (root maggots), Hypoderma linea (scales), Saissetia oleae (black scale), Schizaphis graminum tum (common cattle grub), Liriomyza spp. (leafminer flies), 5 (greenbug), Sitobion avenae (English grain aphid), Sogatella Liriomyza brassica (serpentine leafminer), Mellophagus Ovi fircifera (white-backed planthopper). Therioaphis spp. nus (sheep ked), Musca spp. (muscid flies), Musca autumna (aphids), Toumeyella spp. (scales), Toxoptera spp. (aphids), lis (face fly), Musca domestica (house fly), Oestrus Ovis Trialeurodes spp. (whiteflies), Trialeurodes vaporariorum (sheep bot fly), Oscinella frit (fit fly), Pegomyia betae (beet (greenhouse whitefly), Trialeurodes abutiloneus (banded leafminer), Phorbia spp., Psila rosae (carrotrust fly), Rhago 10 wing whitefly). Unaspis spp. (scales), Unaspis vanonensis letis cerasi (cherry fruit fly), Rhagoletis pomonella (apple (arrowhead scale), and Zulia entreriana. maggot), Sitodiplosis mosellana (orange wheat blossom In another embodiment, the invention disclosed in this midge), Stomoxys calcitrans (stable fly), Tabanus spp. (horse document can be used to control Hymenoptera (ants, wasps, flies), and Tipula spp. (crane flies). and bees). A non-exhaustive list of these pests includes, but is In another embodiment, the invention disclosed in this 15 not limited to, Acromyrrmex spp., Athalia rosae, Atta spp. document can be used to control Hemiptera (true bugs). A (leafcutting ants), Camponotus spp. (carpenterants), Diprion non-exhaustive list of these pests includes, but is not limited spp. (sawflies), Formica spp. (ants), Iridomyrmex humilis to. Acrosternum hilare (green Stink bug), Blissus leucopterus (Argentine ant), Monomorium ssp., Monomorium minumum (chinch bug), Calocoris norvegicus (potato mirid), Cimex (little black ant), Monomorium pharaonis (Pharaoh ant), hemipterus (tropical bedbug), Cimex lectularius (bed bug), Neodiprion spp. (sawflies), Pogonomyrmex spp. (harvester Dagbertus fasciatus, Dichelops furcatus, Dysdercus suturel ants), Polistes spp. (paper wasps), Solenopsis spp. (fire ants), lus (cotton stainer), Edessa meditabunda, Eurygaster maura Tapoinoma sessile (odorous house ant), Tetranomorium spp. (cereal bug), Euschistus heros, Euschistus servus (brown (pavementants), Vespula spp. (yellowjackets), and Xylocopa Stink bug), Helopeltis antonii, Helopeltis theivora (tea blight spp. (carpenter bees). plantbug), Lagynotomus spp. (Stink bugs), Leptocorisa Ora 25 In another embodiment, the invention disclosed in this torius, Leptocorisa varicornis, Lygus spp. (plant bugs), Lygus document can be used to control Isoptera (termites). A non hesperus (western tarnished plant bug), Maconellicoccus hir exhaustive list of these pests includes, but is not limited to, sutus, Neurocolpus longirostris, Nezara viridula (Southern Coptotermes spp., Coptotermes curvignathus, Coptotermes green Stink bug), Phytocoris spp. (plant bugs), Phytocoris frenchi, Coptotermes formosanus (Formosan Subterranean Californicus, Phytocoris relativus, Piezodorus guildingi, 30 termite), Cornitermes spp. (nasute termites), Cryptotermes Poecilocapsus lineatus (fourlined plant bug), Psallus vaccini spp. (drywood termites), Heterotermes spp. (desert Subterra cola, Pseudacy.sta perseae, Scaptocoris castanea, and Tri nean termites), Heterotermes aureus, Kalotermes spp. (dry atoma spp. (bloodsucking conenose bugs/kissing bugs). wood termites), Incistitermes spp. (drywood termites), Mac In another embodiment, the invention disclosed in this rotermes spp. (fungus growing termites), Marginitermes spp. document can be used to control Homoptera (aphids, Scales, 35 (drywood termites), Microcerotermes spp. (harvester ter whiteflies, leafhoppers). A non-exhaustive list of these pests mites), Microtermes obesi, Procornitermes spp., Reticuliter includes, but is not limited to, Acrythosiphon pisum (pea mes spp. (Subterranean termites), Reticulitermes banyulensis, aphid), Adelges spp. (adelgids), Aleurodes proletella (cab Reticulitermes grassei, Reticulitermes flavipes (eastern Sub bage whitefly), Aleurodicus disperses, Aleurothrixus flocco terranean termite), Reticulitermes hageni, Reticulitermes sus (woolly whitefly), Aluacaspis spp., Amrasca biguitella 40 hesperus (western Subterranean termite), Reticulitermes San biguitella, Aphrophora spp. (leafhoppers), Aonidiella aurantii tonensis, Reticulitermes speratus, Reticulitermes tibialis, (California red scale), Aphis spp. (aphids), Aphis gossypii Reticulitermes virginicus, Schedorhinotermes spp., and Zoo (cotton aphid), Aphis pomi (apple aphid), Aulacorthum Solani termopsis spp. (rotten-wood termites). (foxglove aphid), Bemisia spp. (whiteflies), Bemisia argenti In another embodiment, the invention disclosed in this folii, Bemisia tabaci (sweetpotato whitefly), Brachycolus 45 document can be used to control Lepidoptera (moths and noxius (Russian aphid), Brachycorynella asparagi (aspara butterflies). A non-exhaustive list of these pests includes, but gus aphid), Brevennia rehi, Brevicoryne brassicae (cabbage is not limited to, Achoea janata, Adoxophyes spp., Adoxo aphid), Ceroplastes spp. (scales), Ceroplastes rubens (red phyes Orana, Agrotis spp. (cutworms), Agrotis ipsilon (black wax scale), Chionaspis spp. (scales), Chrysomphalus spp. cutworm), Alabama argillacea (cotton leafworm), Amorbia (scales), Coccus spp. (scales), Dysaphis plantaginea (rosy 50 cuneana, Amyelosis transitella (navel orangeworm), Ana apple aphid), Empoasca spp. (leafhoppers), Eriosoma lani camptodes defectaria, Anarsia lineatella (peach twig borer), gerum (woolly apple aphid), Icerva purchasi (cottony cush Anomis Sabulifera (jute looper), Anticarsia gemmatalis (vel ion scale), Idioscopus initidulus (mango leafhopper), Laodel vetbean caterpillar), Archips argyrospila (fruittree leafroller), phax striatellus (Smaller brown planthopper), Lepidosaphes Archips rosana (rose leafroller), Argyrotaenia spp. (tortricid spp., Macrosiphum spp., Macrosiphum euphorbiae (potato 55 moths), Argyrotaenia citrana (orange tortrix), Autographa aphid), Macrosiphum granarium (English grain aphid), Mac gamma, Bonagota Cranaodes, Borbo cinnara (rice leaf rosiphum rosae (rose aphid), Macrosteles quadrilineatus (as folder), Bucculatrix thurberiella (cotton leafperforator), ter leafhopper), Mahanarva fimbiolata, Metopolophium Caloptilia spp. (leaf miners), Capua reticulana, Carposina dirhodun (rose grain aphid), Mictis longicornis, Myzus per niponensis (peach fruit moth), Chilo spp., Chlumetia trans sicae (green peach aphid), Nephotettix spp. (leafhoppers), 60 versa (mango shoot borer), Choristoneura rosaceana (ob Nephotettix cinctipes (green leafhopper), Nilaparvata lugens liquebanded leafroller), Chrysodeixis spp., Cnaphalocerus (brown planthopper), Parlatoria pergandii (chaff scale), Par medinalis (grass leafroller), Colias spp., Compomorpha latoria Ziziphi (ebony scale), Peregrinus maidis (corn delpha cramerella, Cossus Cossus (carpenter moth), Crambus spp. cid), Philaenus spp. (spittlebugs), Phylloxera vitifoliae (Sod webworms), Cydia funebrana (plum fruit moth), Cydia (grape phylloxera), Physokermes piceae (spruce bud scale), 65 molesta (oriental fruit moth), Cydia nignicana (pea moth), Planococcus spp. (mealybugs), Pseudococcus spp. (mealy Cydia pomonella (codling moth), Darna diducta, Diaphania bugs), Pseudococcus brevipes (pine apple mealybug), Ouad spp. (stem borers), Diatraea spp. (stalk borers), Diatraea US 8,349,815 B2 21 22 saccharalis (Sugarcane borer), Diatraea graniosella (South (angularwinged katydid), Pterophylla spp. (kaydids), chisto wester corn borer), Earias spp. (bollworms), Earias insulata cerca gregaria, Scudderia furcata (forktailed bush katydid), (Egyptian bollworm), Earias vitella (rough northern boll and Valanga nigricorni. worm), Ecdytopopha aurantianum, Elasmopalpus lignosel In another embodiment, the invention disclosed in this lus (lesser cornstalk borer), Epiphysia's postruttana (light document can be used to control Phthiraptera (Sucking lice). brown apple moth), Ephestia spp. (flour moths), Ephestia A non-exhaustive list of these pests includes, but is not lim cautella (almond moth), Ephestia elutella (tobbaco moth), ited to, Haematopinus spp. (cattle and hog lice), Linognathus Ephestia kuehniella (Mediterranean flour moth), Epimeces Ovillus (sheep louse), Pediculus humanus capitis (human spp., Epinotia aporema, Erionota thrax (banana skipper), body louse), Pediculus humanus humanus (human body lice), Eupoecilia ambiguella (grape berry moth), Euxoa auxiliaris 10 and Pthirus pubis (crab louse), In another embodiment, the invention disclosed in this (army cutworm), Feltia spp. (cutworms), Gortyna spp. (stem document can be used to control Siphonaptera (fleas). A borers), Grapholita molesta (oriental fruit moth), Hedylepta non-exhaustive list of these pests includes, but is not limited indicata (bean leaf webber), Helicoverpa spp. (noctuid to, Ctenocephalides canis (dog flea), Ctenocephalides felis moths), Helicoverpa armigera (cotton bollworm), Helicov 15 (cat flea), and Pulex irritans (human flea). erpa zea (bollworm/corn earworm), Heliothis spp. (noctuid In another embodiment, the invention disclosed in this moths), Heliothis virescens (tobacco budworm), Hellula document can be used to control Thysanoptera (thrips). A undalis (cabbage webworm), Indarbela spp. (root borers), non-exhaustive list of these pests includes, but is not limited Keiferia lycopersicella (tomato pinworm), Leucinodes to, Frankliniella fisca (tobacco thrips), Frankliniella occi Orbonalis (eggplant fruit borer), Leucoptera malifoliella, dentalis (western flower thrips), Frankliniella Shultzei Fran Lithocollectis spp., Lobesia botrana (grapefruit moth), Loxia Kliniella williamsi (corn thrips), Heliothrips haemorrhaidalis grotis spp. (noctuid moths), Loxagrotis albicosta (western (greenhouse thrips), Riphiphorothrips cruentatus, Scirto bean cutworm), Lymantria dispar (gypsy moth), Lyonetia thrips spp., Scirtothrips citri (citrus thrips), Scirtothrips dor clerkella (apple leaf miner), Mahasena corbetti (oil palm salis (yellow tea thrips), Taeniothrips rhopalantennalis, and bagworm), Malacosoma spp. (tent caterpillars), Mamestra 25 Thrips spp. brassicae (cabbage armyworm), Maruca testulalis (bean pod In another embodiment, the invention disclosed in this borer), Metisa plana (bagworm), Mythinna unipuncta (true document can be used to control Thysanura (bristletails). A armyworm), Neoleucinodes elegantalis (Small tomato borer), non-exhaustive list of these pests includes, but is not limited Nymphula depunctalis (rice caseworm), Operophthera bru to, Lepisma spp. (silverfish) and Thermobia spp. (firebrats). mata (winter moth), Ostrinia nubilalis (European corn 30 In another embodiment, the invention disclosed in this document can be used to control Acarina (mites and ticks). A borer), Oxydia vesulia, Pandemis cerasana (common currant non-exhaustive list of these pests includes, but is not limited tortrix), Pandemis heparana (brown apple tortrix), Papilio to, Acarapsis woodi (tracheal mite of honeybees), Acarus demodocus, Pectinophora gossypiella (pink bollworm), spp. (food mites), Acarus siro (grain mite), Aceria Peridroma spp. (cutworms), Peridroma saucia (variegated 35 mangiferae (mango bud mite), Aculops spp., Aculops lyco cutworm), Perileucoptera coffeella (white coffee leafminer), persici (tomato russet mite), Aculops pelekasi, Aculus pelle Phthorimaea operculella (potato tuber moth), Phyllocnisitis kassi, Aculus Schlechtendali (apple rust mite), Amblyomma citrella, Phyllonorycter spp. (leafminers), Pieris rapae (im americanum (lone startick), Boophilus spp. (ticks), Brevipal ported cabbageworm), Plathypena scabra, Plodia interpunc pus Obovatus (privet mite), Brevipalpus phoenicis (red and tella (Indian meal moth), Plutella xylostella (diamondback 40 black flat mite), Demodex spp. (mange mites), Dermacentor moth), Polychrosis viteana (grape berry moth), Prays spp. (hard ticks), Dermacentor variabilis (american dog endocarpa, Prays oleae (olive moth), Pseudaletia spp. (noc tick), Dermatophagoides pteronyssinus (house dust mite), tuid moths), Pseudaletia unipunctata (armyworm), Eotetranycus spp., Eotetranychus carpini (yellow spider Pseudoplusia includens (soybean looper), Rachiplusia nu, mite), Epitimerus spp., Eriophyes spp., Ixodes spp. (ticks), Scirpophaga incertulas, Sesamia spp. (stemborers), Sesamia 45 Metatetranycus spp., Notoedres cati, Oligonychus spp., Oli inferens (pink rice stem borer), Sesamia nonagrioides, Setora gonychus coffee, Oligonychus ilicus (Southern red mite), nitens, Sitotroga cerealella (Angoumois grain moth), Spar Panonychus spp., Panonychus citri (citrus red mite), Panony ganothis pilleriana, Spodoptera spp. (armyworms), chus ulmi (European red mite), Phylocoptruta oleivora (cit Spodoptera exigua (beet armyworm), Spodoptera fugiperda rus rust mite), Polyphagotarisonemun latus (broad mite), Rhi (fall armyworm), Spodoptera oridania (Southern army 50 picephalus sanguineus (brown dog tick), Rhizoglyphus spp. worm), Synanthedon spp. (root borers). Thecla basilides, (bulb mites), Sarcoptes scabiei (itch mite), Tegolophus per Thermisia gemmatalis, Tineola bisselliella (webbing clothes seaflorae, Tetranychus spp., Tetranychus urticae (twospotted moth), Trichoplusia ni (cabbage looper), Tuta absoluta, spider mite), and Varroa destructor (honeybee mite). Yponomeuta spp., Zeuzera coffeae (red branch borer), and In another embodiment, the invention disclosed in this Zeuzera pyrina (leopard moth). 55 document can be used to control Nematoda (nematodes). A In another embodiment, the invention disclosed in this non-exhaustive list of these pests includes, but is not limited document can be used to control Mallophaga (chewing lice). to, Aphelenchoides spp. (bud and leaf & pine wood nema A non-exhaustive list of these pests includes, but is not lim todes), Belonolaimus spp. (sting nematodes), Criconemella ited to, Bovicola Ovis (sheep biting louse), Menacanthus stra spp. (ring nematodes), Dirofilaria immitis (dog heartwom), mineus (chicken body louse), and Menopon gallinea (com 60 Dity lenchus spp. (stem and bulb nematodes), Heterodera spp. mon hen house). (cyst nematodes), Heterodera zeae (corn cyst nematode), In another embodiment, the invention disclosed in this Hirschmanniella spp. (root nematodes), Hoplolaimus spp. document can be used to control Orthoptera (grasshoppers, (lance nematodes), Meloidogyne spp. (root knot nematodes), locusts, and crickets). A non-exhaustive list of these pests Meloidogyne incognita (root knot nematode). Onchocerca includes, but is not limited to, Anabrus simplex (Mormon 65 volvulus (hook-tail worm), Pratylenchus spp. (lesion nema cricket), Gryllotalpidae (mole crickets), Locusta migratoria, todes), Radopholus spp. (burrowing nematodes), and Roty Melanoplus spp. (grasshoppers), Microcentrum retinerve lenchus reniformis (kidney-shaped nematode). US 8,349,815 B2 23 24 In another embodiment, the invention disclosed in this methyl, ethoprophos, ethyl DDD, ethyl formate, ethylene document can be used to control Symphyla (Symphylans). A dibromide, ethylene dichloride, ethylene oxide, etofenprox. non-exhaustive list of these pests includes, but is not limited etoxazole, etrimfos, EXD, to, Scutigerella immaculata. famphur, fenamiphos, fenaZaflor, fenaZaquin, fenbutatin For more detailed information consult “Handbook of Pest 5 oxide, fenchlorphos, fenethacarb, fenfluthrin, fenitrothion, Control The Behavior, Life Histroy, and Control of House fenobucarb, fenothiocarb, fenoxacrim, fenoxycarb, fen hold Pests” by Arnold Mallis, 9th Edition, copyright 2004 by pirithrin, fenpropathrin, fenpyroximate, fenson, fensul GIE Media Inc. fothion, fenthion, fenthion ethyl, fentrifanil, fenvalerate, fipronil, flonicamid, fluacrypyrim, fluaZuron, flubendiamide, Mixtures 10 flubenzimine, flucofuron, flucycloxuron, flucythrinate, flu enetil, flufenerim, flufenoxuron, flufenprox, flumethrin, flu Some of the pesticides that can be employed beneficially in orbenside, fluvalinate, fonofos, formetanate, formothion, combination with the invention disclosed in this document formparanate, foSmethilan, fospirate, fosthiazate, fosthietan, fosthietan, furathiocarb, furethrin, furfural, include, but are not limited to the following: 15 gamma cyhalothrin, gamma HCH, 1.2 dichloropropane, 1.3 dichloropropene, halfenprox, halofenozide, HCH, HEOD, heptachlor, hep abamectin, acephate, acequinocyl, acetamiprid, acethion, tenophos, heterophos, hexaflumuron, hexythiazox, HHDN. acetoprole, acrinathrin, acrylonitrile, alanycarb, aldicarb, hydramethylnon, hydrogen cyanide, hydroprene, hyduin aldoxycarb, aldrin, allethrin, allosamidin, allyxycarb, alpha carb, cypermethrin, alpha ecdysone, amidithion, amidoflumet, imicyafos, imidacloprid, imiprothrin, indoxacarb, aminocarb, amiton, amitraz, anabasine, arsenous oxide, athi iodomethane, IPSP, isamidofos, isazofos, isobenzan, isocar dathion, azadirachtin, azamethiphos, azinphos ethyl, azin bophos, isodrin, isofenphos, isoprocarb, isoprothiolane, phos methyl, azobenzene, azocyclotin, azothoate, isothioate, isoxathion, ivermectin barium hexafluorosilicate, barthrin, benclothiaz, bendio jasmolin I, jasmolin II, jodfenphos, juvenile hormone I, carb, benfuracarb, benomyl, benoxafos, benSultap, benzoxi 25 juvenile hormone II, juvenile hormone III, mate, benzyl benzoate, beta cyfluthrin, beta cypermethrin, kelevan, kinoprene, bifenazate, bifenthrin, binapacryl, bioallethrin, bioetha lambda cyhalothrin, lead arsenate, lepimectin, leptophos, nomethrin, biopermethrin, bistrifluoron, borax, boric acid, lindane, lirimfos, lufenuron, lythidathion, bromfenVinfos, bromo DDT, bromocyclen, bromophos, bro malathion, malonoben, mazidox, mecarbam, mecarphon, mophos ethyl, bromopropylate, bufencarb, buprofezin, 30 menazon, mephosfolan, mercurous chloride, mesulfen, butacarb, butathiofos, butocarboxim, butonate, butoxycar meSulfenfos, metaflumizone, metam, methacrifos, methami boxim, dophos, methidathion, methiocarb, methocrotophos, meth cadusafos, calcium arsenate, calcium polysulfide, cam omyl, methoprene, methoxychlor, methoxyfenozide, methyl phechlor, carbanolate, carbaryl, carbofuran, carbon disulfide, bromide, methyl isothiocyanate, methylchloroform, methyl carbon tetrachloride, carbophenothion, carbosulfan, cartap, 35 ene chloride, metofluthrin, metolcarb, metoxadiaZone, chinomethionat, chlorantraniliprole, chlorbenside, chlorbi mevinphos, mexacarbate, milbemectin, milbemycin oxime, cyclen, chlordane, chlordecone, chlordimeform, chlore mipafox, mirex, MNAF, monocrotophos, morphothion, moX thoxyfos, chlorfeinapyr, chlorfenethol, chlorfenson, chlorfen idectin, Sulphide, chlorfenvinphos, chlorfluaZuron, chlormephos, naftalofos, naled, naphthalene, nicotine, nifluridide, nikko chlorobenzilate, chloroform, chloromebuform, chloromethi 40 mycins, nitenpyram, nithiazine, nitrilacarb, novaluron, novi uron, chloropicrin, chloropropylate, chlorphoxim, chlorpra flumuron, Zophos, chlorpyrifos, chlorpyrifos methyl, chlorthiophos, omethoate, oxamyl, oxydemeton methyl, Oxydeprofos, chromafenozide, cinerin I, cinerin II, cismethrin, cloetho oXydisulfoton, carb, clofentezine, closantel, clothianidin, copper acetoarsen paradichlorobenzene, parathion, parathion methyl, pen ite, copper arsenate, copper naphthenate, copper oleate, cou 45 fluoron, pentachlorophenol, permethrin, phenkapton, pheno maphos, coumithoate, crotamiton, crotoxyphos, cruentaren thrin, phenthoate, phorate, phosalone, phosfolan, phosmet, A&B, crufomate, cryolite, cyanofenphos, cyanophos, cyan phosnichlor, phosphamidon, phosphine, phosphocarb, thoate, cyclethrin, cycloprothrin, cyenopyrafen, cyflu phoxim, phoxim methyl, pirimetaphos, pirimicarb, pirimi metofen, cyfluthrin, cyhalothrin, cyhexatin, cypermethrin, phos ethyl, pirimiphos methyl, potassium arsenite, potassium cyphenothrin, cyromazine, cythioate, 50 thiocyanate, pp' DDT, prallethrin, precocene I, precocene II, d-limonene, dazomet, DBCP, DCIP, DDT, decarbofuran, precocene III, primidophos, proclonol, profenofos, prof deltamethrin, demephion, demephion O. demephion S. luthrin, promacyl, promecarb, propaphos, propargite, pro demeton, demeton methyl, demeton O, demeton O methyl, petamphos, propoXur, prothidathion, prothiofos, prothoate, demeton S, demeton S methyl, demeton S methylsulphon, protrifenbute, pyraclofos, pyrafluprole, pyrazophos, pyres diafenthiuron, dialifos, diamidafos, diazinon, dicapthon, 55 methrin, pyrethrin I, pyrethrin II, pyridaben, pyridalyl, dichlofenthion, dichlofluanid, dichlorvos, dicofol, dicresyl pyridaphenthion, pyrifluquinazon, pyrimidifen, pyrimitate, dicrotophos, dicyclanil, dieldrin, dienochlor, diflovidazin, pyriprole, pyriproxyfen, diflubenzuron, dilor, dimefluthrin, dimefox, dimetan, quassia, quinalphos, quinalphos, quinalphos methyl, dimethoate, dimethrin, dimethylvinphos, dimetilan, dinex, quinothion, quantifies, dinobuton, dinocap, dinocap 4, dinocap 6, dinocton, dinopen 60 rafoxanide, resmethrin, rotenone, ryania, ton, dinoprop, dinosam, dinosulfon, dinotefuran, dinoterbon, Sabadilla, Schradan, Selamectin, Silafluofen, Sodium arsen diofenolan, dioxabenzofos, dioxacarb, dioxathion, diphenyl ite, sodium fluoride, Sodium hexafluorosilicate, Sodium thio sulfone, disulfuram, disulfoton, dithicrofos, DNOC, cyanate, Sophamide, spinetoram, spinosad, spirodiclofen, dofenapyn, doramectin, spiromesifen, spirotetramat, Sulcofuron, Sulfuram, Sulflura ecdysterone, emamectin, EMPC, empenthrin, endosulfan, 65 mid, sulfotep, sulfur, sulfuryl fluoride, Sulprofos, endothion, endrin, EPN, epolfenonane, eprinomectin, esfen tau fluvalinate, tazimcarb, TDE, tebufenozide, tebufen Valerate, etaphos, ethiofencarb, ethion, ethiprole, ethoate pyrad, tebupirimfos, teflubenzuron, tefluthrin, temephos, US 8,349,815 B2 25 26 TEPP, terallethrin, terbufos, tetrachloroethane, tetrachlorvin Such pesticides. Such water-soluble, water-Suspendable, or phos, tetradifon, tetramethrin, tetranactin, tetrasul, theta emulsifiable formulations, are either solids, usually known as cypermethrin, thiacloprid, thiamethoxam, thicrofos, thiocar wettable powders, or water dispersible granules, or liquids boxime, thiocyclam, thiodicarb, thiofanox, thiometon, usually known as emulsifiable concentrates, or aqueous Sus thionazin, thioquinox, thiosultap, thuringiensin, tolfenpyrad, pensions. Wettable powders, which may be compacted to tralomethrin, transfluthrin, transpermethrin, triarathene, tri form water dispersible granules, comprise an intimate mix aZamate, triaZophos, trichlorfon, trichlorimetaphos 3, trichlo ture of the pesticide, a carrier, and Surfactants. The concen ronat, trifenofos, triflumuron, trimethacarb, triprene, 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, 10 attapulgite clays, the montmorillonite clays, the diatoma Zeta cypermethrin and Zolaprofos. ceous earths, or the purified silicates. Effective surfactants, Additionally, any combination of the above pesticides can comprising from about 0.5% to about 10% of the wettable be used. 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 15 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 Emulsifiable concentrates of pesticides comprise a conve antimicrobials, bactericides, defoliants, safeners, synergists, 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 molluscicides (these categories not necessarily mutually immiscible organic solvent and emulsifiers. Useful organic exclusive) for reasons of economy, and synergy. Solvents include aromatics, especially Xylenes and petroleum For more information consult “Compendium of Pesticide fractions, especially the high-boiling naphthalenic and ole Common Names' located at http://www.alanwood.net/pesti finic portions of petroleum Such as heavy aromatic naphtha. cides/index.html as of the filing date of this document. Also 25 Other organic Solvents may also be used, such as the terpenic consult “The Pesticide Manual 14' Edition, edited by CDS Solvents including rosin derivatives, aliphatic ketones Such as Tomlin, copyright 2006 by British Crop Production Council. cyclohexanone, and complex alcohols such as 2-ethoxyetha nol. Suitable emulsifiers for emulsifiable concentrates are Synergistic Mixtures chosen from conventional anionic and nonionic Surfactants. 30 Aqueous Suspensions comprise Suspensions of water-in The invention disclosed in this document can be used with soluble pesticides dispersed in an aqueous carrier at a con other compounds such as the ones mentioned under the head centration in the range from about 5% to about 50% by ing “Mixtures” to form synergistic mixtures where the mode weight. Suspensions are prepared by finely grinding the pes of action of the compounds in the mixtures are the same, ticide and vigorously mixing it into a carrier comprised of similar, or different. 35 water and Surfactants. Ingredients, such as inorganic salts and Examples of mode of actions include, but are not limited to: synthetic or natural gums, may also be added, to increase the acetylcholine esterase inhibitor, Sodium channel modulator, density and Viscosity of the aqueous carrier. It is often most chitin biosynthesis inhibitor; GABA-gated chloride channel effective to grind and mix the pesticide at the same time by antagonist; GABA and glutamate-gated chloride channel preparing the aqueous mixture and homogenizing it in an agonist; acetyl choline receptor agonist; MET I inhibitor; 40 implement Such as a sand mill, ball mill, or piston-type Mg-stimulated ATPase inhibitor; nicotinic acetylcholine homogenizer. receptor, Midgut membrane disrupter; and oxidative phos Pesticides may also be applied as granular compositions phorylation disrupter. that are particularly useful for applications to the soil. Granu Additionally, the following compounds are known as Syn lar compositions usually contain from about 0.5% to about ergists and can be used with the invention disclosed in this 45 10% by weight of the pesticide, dispersed in a carrier that document: piperonylbutoxide, piprotal, propyl isome, sesa comprises clay or a similar Substance. Such compositions are mex, Sesamolin, and Sulfoxide. usually prepared by dissolving the pesticide in a Suitable Solvent and applying it to a granular carrier which has been Formulations pre-formed to the appropriate particle size, in the range of 50 from about 0.5 to 3 mm. Such compositions may also be A pesticide is rarely suitable for application in its pure formulated by making a dough or paste of the carrier and form. It is usually necessary to add other Substances so that compound and crushing and drying to obtain the desired the pesticide can be used at the required concentration and in granular particle size. an appropriate form, permitting ease of application, handling, Dusts containing a pesticide are prepared by intimately transportation, storage, and maximum pesticide activity. 55 mixing the pesticide in powdered form with a suitable dusty Thus, pesticides are formulated into, for example, baits, con agricultural carrier, Such as kaolin clay, ground Volcanic rock, centrated emulsions, dusts, emulsifiable concentrates, fumi and the like. Dusts can suitably contain from about 1% to gants, gels, granules, microencapsulations, seed treatments, about 10% of the pesticide. They can be applied as a seed Suspension concentrates, Suspoemulsions, tablets, water dressing, or as a foliage application with a dust blower soluble liquids, water dispersible granules or dry flowables, 60 machine. wettable powders, and ultra low volume solutions. It is equally practical to apply a pesticide in the form of a For further information on formulation types see “Cata Solution in an appropriate organic solvent, usually petroleum logue of pesticide formulation types and international coding oil. Such as the spray oils, which are widely used in agricul system’Technical Monograph n° 2, 5th Edition by CropLife tural chemistry. International (2002). 65 Pesticides can also be applied in the form of an aerosol Pesticides are applied most often as aqueous Suspensions composition. In Such compositions the pesticide is dissolved or emulsions prepared from concentrated formulations of or dispersed in a carrier, which is a pressure-generating pro US 8,349,815 B2 27 28 pellant mixture. The aerosol composition is packaged in a A wetting agent is a Substance that when added to a liquid container from which the mixture is dispensed through an increases the spreading or penetration power of the liquid by atomizing valve. reducing the interfacial tension between the liquid and the Pesticide baits are formed when the pesticide is mixed with Surface on which it is spreading. Wetting agents are used for food oran attractant or both. When the pests eat the bait they 5 two main functions in agrochemical formulations: during also consume the pesticide. Baits may take the form of gran processing and manufacture to increase the rate of wetting of ules, gels, flowable powders, liquids, or Solids. They are use in powders in water to make concentrates for soluble liquids or pest harborages. Suspension concentrates; and during mixing of a product with Fumigants are pesticides that have a relatively high vapor water in a spray tank to reduce the wetting time of wettable pressure and hence can exist as a gas in Sufficient concentra- 10 powders and to improve the penetration of water into water tions to kill pests in soil or enclosed spaces. The toxicity of the dispersible granules. Examples of wetting agents used in fumigant is proportional to its concentration and the exposure wettable powder, Suspension concentrate, and water-dispers time. They are characterized by a good capacity for diffusion ible granule formulations are: sodium lauryl Sulphate; sodium and act by penetrating the pest's respiratory system or being dioctyl Sulphosuccinate; alkyl phenol ethoxylates; and ali absorbed through the pest’s cuticle. Fumigants are applied to 15 phatic alcohol ethoxylates. control stored product pests under gas proof sheets, in gas A dispersing agent is a Substance which adsorbs onto the sealed rooms or buildings or in special chambers. Surface of a particles and helps to preserve the state of dis Pesticides can be microencapsulated by Suspending the persion of the particles and prevents them from reaggregat pesticide particles or droplets in plastic polymers of various ing. Dispersing agents are added to agrochemical formula types. By altering the chemistry of the polymer or by chang- 20 tions to facilitate dispersion and Suspension during ing factors in the processing, microcapsules can be formed of manufacture, and to ensure the particles redisperse into water various sizes, Solubility, wall thicknesses, and degrees of in a spray tank. They are widely used in wettable powders, penetrability. These factors govern the speed with which the Suspension concentrates and water-dispersible granules. Sur active ingredient within is released, which. in turn, affects the factants that are used as dispersing agents have the ability to residual performance, speed of action, and odor of the prod- 25 adsorb strongly onto a particle Surface and provide a charged uct. or steric barrier to reaggregation of particles. The most com Oil Solution concentrates are made by dissolving pesticide monly used surfactants are anionic, non-ionic, or mixtures of in a solvent that will hold the pesticide in solution. Oil solu the two types. For wettable powder formulations, the most tions of a pesticide usually provide faster knockdown and kill common dispersing agents are sodium lignoSulphonates. For of pests than other formulations due to the solvents them- 30 Suspension concentrates, very good adsorption and stabiliza selves having pesticidal action and the dissolution of the tion are obtained using polyelectrolytes, such as Sodium waxy covering of the integument increasing the speed of naphthalene sulphonate formaldehyde condensates. uptake of the pesticide. Other advantages of oil solutions Tristyrylphenol ethoxylate phosphate esters are also used. include better storage stability, better penetration of crevices, Non-ionics such as alkylarylethylene oxide condensates and and better adhesion to greasy Surfaces. 35 EO-PO block copolymers are sometimes combined with Another embodiment is an oil-in-water emulsion, wherein anionics as dispersing agents for Suspension concentrates. In the emulsion comprises oily globules which are each pro recent years, new types of very high molecular weight poly vided with a lamellar liquid crystal coating and are dispersed meric Surfactants have been developed as dispersing agents. in an aqueous phase, wherein each oily globule comprises at These have very long hydrophobic backbones and a large least one compound which is agriculturally active, and is 40 number of ethylene oxide chains forming the teeth of a individually coated with a monolamellar or oligolamellar comb surfactant. These high molecular weight polymers layer comprising: (1) at least one non-ionic lipophilic Sur can give very good long-term stability to Suspension concen face-active agent, (2) at least one non-ionic hydrophilic Sur trates because the hydrophobic backbones have many anchor face-active agent and (3) at least one ionic Surface-active ing points onto the particle Surfaces. Examples of dispersing agent, wherein the globules having a mean particle diameter 45 agents used in agrochemical formulations are: Sodium ligno of less than 800 nanometers. Further information on the Sulphonates; Sodium naphthalene Sulphonate formaldehyde embodiment is disclosed in U.S. patent publication condensates; tristyrylphenol ethoxylate phosphate esters; ali 20070027034 published Feb. 1, 2007, having patent applica phatic alcohol ethoxylates; alky ethoxylates; EO-PO block tion Ser. No. 1 1/495,228. For ease of use this embodiment copolymers; and graft copolymers. will be referred to as “OIWE. 50 An emulsifying agent is a Substance which stabilizes a For further information consult “Insect Pest Management” Suspension of droplets of one liquid phase in another liquid 2' Edition by D. Dent, copyright CAB International (2000). phase. Without the emulsifying agent the two liquids would Additionally, for more detailed information consult “Hand separate into two immiscible liquid phases. The most com book of Pest Control The Behavior, Life Histroy, and Con monly used emulsifier blends contain alkylphenol oraliphatic trol of Household Pests” by Arnold Mallis, 9" Edition, copy- 55 alcohol with 12 or more ethylene oxide units and the oil right 2004 by GIE Media Inc. soluble calcium salt of dodecylbenzene sulphonic acid. A range of hydrophile-lipophile balance (“HLB) values from 8 Other Formulation Components to 18 will normally provide good stable emulsions. Emulsion stability can sometimes be improved by the addition of a Generally, the invention disclosed in this document when 60 small amount of an EO-PO block copolymer surfactant. used in a formulation, such formulation can also contain other A solubilizing agent is a Surfactant which will form components. These components include, but are not limited micelles in water at concentrations above the critical micelle to, (this is a non-exhaustive and non-mutually exclusive list) concentration. The micelles are then able to dissolve or solu wetters, spreaders, Stickers, penetrants, buffers, sequestering bilized water-insoluble materials inside the hydrophobic part agents, drift reduction agents, compatibility agents, anti- 65 of the micelle. The type of surfactants usually used for solu foam agents, cleaning agents, and emulsifiers. A few compo bilization are non-ionics: Sorbitan monooleates; Sorbitan nents are described forthwith. monooleate ethoxylates; and methyl oleate esters. US 8,349,815 B2 29 30 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 ticides in Agriculture and Environment—Retrospects and bioenhancement depend generally on the nature and mode of 5 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 material added to the pesticide to give a product of the 10 The actual amount of pesticide to be applied to loci of pests required strength. Carriers are 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 hectare are expected to provide good control. water-dispersible granules. 15 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 emulsifiable 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 first main groups of solvents are aliphatic around buildings. paraffinic oils such as kerosene or refined paraffins. 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 matic solvents such as Xylene and higher molecular weight bait. Baits can also be applied to a Surface of a building, fractions of C and Co aromatic solvents. Chlorinated hydro (horizontal, Vertical, or slant, Surface) where, for example, carbons are useful as cosolvents to prevent crystallization of ants, termites, cockroaches, and flies, can come into contact pesticides when the formulation is emulsified into water. 25 with the bait. Alcohols are sometimes used as cosolvents to increase sol Because of the unique ability of the eggs of some pests to vent power. resist pesticides repeated applications may be desirable to Thickeners or gelling agents are used mainly in the formu control newly emerged larvae. lation of suspension concentrates, emulsions and Suspoemul Systemic movement of pesticides in plants may be utilized sions to modify the rheology or flow properties of the liquid 30 to control pests on one portion of the plant by applying the and to prevent separation and settling of the dispersed par pesticides to a different portion of the plant. For example, ticles or droplets. Thickening, gelling, and anti-settling control of foliar-feeding insects can be controlled by drip agents generally fall into two categories, namely water-in irrigation or furrow application, or by treating the seed before soluble particulates and water-soluble polymers. It is possible planting. Seed treatment can be applied to all types of seeds, to produce Suspension concentrate formulations using clays 35 including those from which plants genetically transformed to and silicas. Examples of these types of materials, include, but express specialized traits will germinate. Representative are limited to, montmorillonite, e.g. bentonite; magnesium examples include those expressing proteins toxic to inverte aluminum silicate; and attapulgite. Water-soluble polysac brate pests, such as Bacillus thuringiensis or other insecti charides have been used as thickening-gelling agents for cidal toxins, those expressing herbicide resistance, such as many years. The types of polysaccharides most commonly 40 “Roundup Ready seed, or those with “stacked' foreign used are natural extracts of seeds and seaweeds or are syn genes expressing insecticidal toxins, herbicide resistance, thetic derivatives of cellulose. Examples of these types of nutrition-enhancement or any other beneficial traits. Further materials include, but are not limited to, guar gum, locust more, Such seed treatments with the invention disclosed in bean gum, carrageenam; alginates; methyl cellulose; sodium this document can further enhance the ability of a plant to carboxymethyl cellulose (SCMC); hydroxyethyl cellulose 45 better withstand stressful growing conditions. This results in (HEC). Other types of anti-settling agents are based on modi a healthier, more vigorous plant, which can lead to higher fied Starches, polyacrylates, polyvinyl alcohol and polyethyl yields at harvest time. ene oxide. Another good anti-settling agent is Xanthan gum. The invention disclosed in this document is suitable for Microorganisms which cause spoilage of formulated prod controlling endoparasites and ectoparasites in the Veterinary ucts. Therefore preservation agents are used to eliminate or 50 medicine sector or in the field of animal keeping. Compounds reduce their effect. Examples of such agents include, but are according to the invention are applied here in a known man limited to propionic acid and its Sodium salt; Sorbic acid and ner, such as by oral administration in the form of for example, its sodium or potassium salts; benzoic acid and its sodium tablets, capsules, drinks, granules, by dermal application in salt; p-hydroxybenzoic acid sodium salt; methyl p-hydroxy the form of for example, dipping, spraying, pouring on, spot benzoate; and 1,2-benzisothiazalin-3-one (BIT). 55 ting on, and dusting, and by parenteral administration in the The presence of surfactants, which lower interfacial ten form of for example, an injection. Sion, often causes water-based formulations to foam during The invention disclosed in this document can also be mixing operations in production and in application through a employed advantageously in livestock keeping, for example, spray tank. In order to reduce the tendency to foam, anti-foam cattle, sheep, pigs, chickens, and geese. Suitable formulations agents are often added either during the production stage or 60 are administered orally to the animals with the drinking water before filling into bottles. Generally, there are two types of or feed. The dosages and formulations that are suitable anti-foam agents, namely silicones and non-silicones. Sili depend on the species. cones are usually aqueous emulsions of dimethyl polysilox The invention disclosed in this document can also be used ane while the non-silicone anti-foam agents are water-in Before a pesticide can be used or sold commercially, Such soluble oils, such as octanol and nonanol, or silica. In both 65 pesticide undergoes lengthy evaluation processes by various cases, the function of the anti-foam agent is to displace the governmental authorities (local, regional, state, national, surfactant from the air-water interface. international). Voluminous data requirements are specified by US 8,349,815 B2 31 32 regulatory authorities and must be addressed through data -continued generation and Submission by the product registrant or by Compound 2 another on the product registrant's behalf. These governmen tal authorities then review such data and if a determination of safety is concluded, provide the potential user or seller with 5 N s1 product registration approval. Thereafter, in that locality / Y CN where the product registration is granted and Supported. Such CF % user or seller may use or sell Such pesticide. 3 What is claimed is: 1. A synergistic pesticidal composition comprising 10 (a) either Compound 1 or Compound 2 al d (b) methoxyfenozide. 4. A synergistic pesticidal composition comprising Compound 1 15 a) eitherither COmoOundlC p d 1 Or CCompoun p d 2 N s1 M V Compound 1 2 O N-CN C N Compound 2 20 N ( 2 /M Y-CN N s1 C N MV 2 / N-CN Compound 2 CF N 25 and N S 1. (b) chlorpyrifos. 2 / Y-CN 2. A synergistic pesticidal composition comprising 30 CF N (a) either Compound 1 or Compound 2 and Compound 1 (b) spinetoram. 1. 35 5. A synergistic pesticidal composition comprising N \ (a) either Compound 1 or Compound 2 2 O N-CN C N Compound 2 40 Compound 1

N S 1. N S 1. /\ MV 2 O N-CN 2 O N-CN CF N 45 C N and Compound 2 (b) gamma cyhalothrin. 3. A synergistic pesticidal composition comprising 50 N s1 (a) either Compound 1 or Compound 2 MV 2 O N-CN CF N Compound 1 55 and N X (b) spinosad. 2 O N-CN C N