MOSQUITO VECTOR CONTROL COMPOSITIONS, METHODS AND PRODUCTS UTILIZING SAME

Abstract

The present inventions concerns use of a certain methoxyacrylate compound to control mosquitoes, and vector control solutions comprising a defined methoxyacrylate compound, in particular the invention relates to a substrate, to a composition, for controlling mosquitoes comprising a defined methoxyacrylate compound, and to certain methoxyacrylate compounds.

Claims

1. A method of controlling mosquitos, comprising: applying to a mosquito, or locus thereof, a compound of Table 1: TABLE-US-00029 TABLE 1 Compound no. 2 (II) 3 (III) 4 (IV) 5 (V) 6 (VI) 7 (VII) 9 (IX) 10 (X) 11 (XI) 12 (XII) 13 (XIII) 14 (XIV) 15 (XV) 16 (XVI) 17 (XVII) 18 (XVIII) 19 (XIX) 20 (XX) 21 (XXI) 22 (XXII) 23 (XXIII)

2. The method according to claim 1, wherein the development of vector-borne diseases are reduced.

3. An integrated mosquito vector control solution comprising one or more methoxyacrylate compounds defined in claim 1.

4. The vector control solution according to claim 3, wherein the solution is a net.

5. The vector control solution according to claim 3, wherein the solution is a composition for coating a net.

6. The vector control solution according to claim 3, wherein the solution is a composition for spraying surfaces of a dwelling.

7. The vector control solution according to claim 3, wherein a further insecticide and/or synergist is present.

8. A polymeric material incorporated with one or more methoxyacrylate compounds defined in claim 1.

9. A kit for treating a fibre, yarn, net and weave by coating wash resistant insecticidal properties thereto comprising: a first sachet comprising a pre-measured amount of at least one compound defined in claim 1, and a second sachet comprising a pre-measured amount of at least one polymeric binder.

10. A method for treating a fibre, yarn, net and weave by coating wash resistant insecticidal properties thereto comprising (i) preparing a treatment composition, which comprises at least one compound defined in claim 1, (ii) treating said fibre, yarn, net and weave and (iii) drying the resulting treated a fibre, yarn, net and weave.

11. A method of preparing a polymeric material impregnated with a compound defined in claim 1, which material is useful for making substrate or non-living material, such as threads, fibres, yarns, pellets, nets and weaves, which method comprises mixing a polymer with a compound defined in claim 1 at a temperature between 120 to 250° C.

12. A method for mosquito vector-control, in particular controlling mosquito vectors carrying pathogenic disease, which method comprises (a) applying an effective amount of a liquid composition comprising a compound defined in claim 1, and a polymeric binder, and optionally, one or more other insecticides, and/or synergists, to a surface of a dwelling; and/or (b) placing a substrate or non-living material incorporated with a compound defined in claim 1, and optionally an additive, one or more other insecticides, and/or synergists, within a dwelling.

13. A net incorporated with a compound defined in claim 1 having a biological activity in accordance with the WHOPES guidelines of a knockdown after 60 minutes of between 95 percent and 100 percent and/or a mortality after 24 hours of between 80 percent and 100 percent after 20 washes.

14. A methoxyacrylate compound listed as compound 3, 5, 9, 11, 13, 14, 16, 17, 19, 20, 21 and 23 in Table 1 as defined in claim 1.

Description

EXAMPLES

Preparation Examples

Example 1: Preparation of methyl (E)-2-[2-[(5-tert-butyl-1,3,4-oxadiazol-2-yl)oxy]phenyl]-3-methoxy-prop-2-enoate (Compound 2)

Step 1: 2-tert-butyl-5-(p-tolylsulfonyl)-1,3,4-oxadiazole

[0216] ##STR00032##

[0217] To a solution of KMnO.sub.4 (1.67 grams, 1.3 equiv., 10.47 mmol) in water (150 ml) was added dropwise a solution of 2-tert-butyl-5-(p-tolylsulfanyl)-1,3,4-oxadiazole (2 g, 8.06 mmol) in glacial acetic acid (30 ml). After 2 h an aqueous solution of sodium metabisulphite was added until the mixture was decolorized. The mixture was filtered and the solid was washed with water, then recrystallized from ethanol to give 2-tert-butyl-5-(p-tolylsulfonyl)-1,3,4-oxadiazole (1.00 g, 3.57 mmol, 44% yield).

Step 2: Methyl (E)-2-[2-[(5-tert-butyl-1,3,4-oxadiazol-2-yl)oxy]phenyl]-3-methoxy-prop-2-enoate

[0218] ##STR00033##

[0219] To a solution of methyl (E)-2-(2-hydroxyphenyl)-3-methoxy-prop-2-enoate (100 mg, 0.48 mmol; prepared as described in Example 3 of EP 0242081 A) in DMF (2 ml) at 0° C. was added 2-tert-butyl-5-(p-tolylsulfonyl)-1,3,4-oxadiazole (404 mg, 3 equiv., 1.44 mmol) and K.sub.2CO.sub.3 (2 equiv., 0.96 mmol).

[0220] The mixture was allowed to warm to room temperature and stirred for 72 h. The mixture was partitioned between diethyl ether and water. The aqueous layer was extracted two times with ether. The combined organic layers were washed with water and brine, dried with MgSO.sub.4, filtered and concentrated under reduced pressure. Column chromatography 100% cyclohexane to cyclohexane/ethyl acetate (70:30) gave methyl (E)-2-[2-[(5-tert-butyl-1,3,4-oxadiazol-2-yl)oxy]phenyl]-3-methoxy-prop-2-enoate (102 mg, 0.30 mmol, 64% yield).

Example 2: Methyl(E)-3-methoxy-2-[2-[[(E)-[(2E)-2-methoxyimino-1-methyl-butylidene]amino]-oxymethyl]phenyl]prop-2-enoate (Compound 4)

Step 1: (2E)-2-Hydroxyiminopentan-3-one

[0221] ##STR00034##

[0222] To a solution of pentan-3-one (6 g, 69.7 mmol) in toluene (30 ml) at 0° C. was added hydrogen chloride (2 mol/L) in diethyl ether (35 ml, 1 equiv., 69.7 mmol, 2 mol/L) dropwise. After the addition was complete a solution of isoamylnitrite (10.7 ml, 1.1 equiv., 76.63 mmol) in diethyl ether (20 ml) was added dropwise. The mixture was stirred at 0° C. for 2 h, then allowed to warm to room temperature and stirred for 16 h. Water (25 ml) was added and the mixture was extracted three times with 2M NaOH. The combined aqueous layers were made slightly acidic with 2M HCl and extracted three times with dichloromethane. The combined organic layers were dried with MgSO.sub.4, filtered and concentrated under reduced pressure to give (2E)-2-hydroxyiminopentan-3-one (5.27 g, 45.8 mmol, 66% yield).

Step 2: (3E)-3-Methoxyiminopentan-2-one Oxime

[0223] ##STR00035##

[0224] To a solution of (2E)-2-hydroxyiminopentan-3-one (2.8 g, 24 mmol) in toluene (30 ml) was added methoxyamine hydrochlorid (40% in H.sub.2O) (1.2 equiv., 29 mmol). The mixture was heated to 65° C. and triethylamine (1.75 equiv., 43 mmol) was added dropwise. The mixture was heated at 65° C. for 3 h. The mixture was cooled to room temperature and acidified with conc. HCl. The organic layer was collected and extracted three times with 2 M NaOH. The combined extracts were made acidic with conc. HCl and extracted three times with ethyl acetate. The combined organic layers were dried with MgSO.sub.4, filtered and concentrated. Column chromatography 100% dichloromethane to dichloromethane/methanol (90:10) gave (3E)-3-methoxyiminopentan-2-one oxime (2.2 g, 15 mmol, 63% yield).

Step 3: Methyl (E)-3-methoxy-2-[2-[[(E)-[(2E)-2-methoxyimino-1-methyl-butylidene]amino]oxymethyl]phenyl]prop-2-enoate

[0225] ##STR00036##

[0226] To a stirred solution of methyl (E)-2-[2-(bromomethyl)phenyl]-3-methoxy-prop-2-enoate (2.5 g, 8.8 mmol; prepared as in J. Agric. Food. Chem, 2007, 55, 5697-5700) in acetone (8 ml) was added (3E)-3-methoxyiminopentan-2-one oxime (1.5 g, 1.2 equiv., 11 mmol) and K.sub.2CO.sub.3 (1.8 g, 1.5 equiv., 13 mmol). The mixture was heated to 60° C. for 72 h. The mixture was cooled to room temperature, filtered and concentrated under reduced pressure. Column chromatography 100% cyclohexane to cyclohexane/ethyl acetate (80:20) gave methyl (E)-3-methoxy-2-[2-[[(E)-[(2E)-2-methoxyimino methyl-butylidene]amino]oxymethyl]-phenyl]prop-2-enoate (1.8 g, 5.2 mmol, —59% yield). Minor impurities were removed by a second chromatography: 100% dichloromethane to dichloromethane/ethyl acetate (95:5).

Example 3: Methyl (E)-2-[2-[(4-tert-butyl-1,3,5-triazin-2-yl)oxy]phenyl]-3-methoxy-prop-2-enoate (Compound 5)

Step 1: N′-cyano-2,2-dimethyl-propenamidine

[0227] ##STR00037##

[0228] The HCl salt of 2,2-dimethylpropanamidine (2.5 g, 18.3 mmol) was dissolved in water (8 ml) and sodium hydrogencyanamide (1.17 g) was added. The mixture was stirred at room temperature for 4 h. The solid was filtered in dried in vacuum to give N′-cyano-2,2-dimethyl-propenamidine (1.17 g, 9.3 mmol, 51%).

Step 2: 2-tert-butyl-4-chloro-1,3,5-triazine

[0229] ##STR00038##

[0230] POCl.sub.3 (1.54 g) was added into dry acetonitrile (10 ml). Dry DMF was added dropwise over 10 minutes. Then N′-cyano-2,2-dimethyl-propanamidine (1.17 g, 9.3 mmol) in dry acetonitrile (25 ml) was added over a period of 25 minutes and the resulting mixture was stirred for 4.5 h at room temperature. The mixture was poured into water (100 ml) and extracted with CH.sub.2Cl.sub.2 (4×40 ml). The combined organic phases were dried with MgSO.sub.4, filtered and concentrated to provide 2-tert-butyl-4-chloro-1,3,5-triazine as an oil (1.15 g, 6.7 mmol, 72%).

Step 3: Methyl (E)-2-[2-[(4-tert-butyl-1,3,5-triazin-2-yl)oxy]phenyl]-3-methoxy-prop-2-enoate

[0231] ##STR00039##

[0232] To a stirred solution of methyl (E)-2-(2-hydroxyphenyl)-3-methoxy-prop-2-enoate (1.54 g, 7.4 mmol; prepared as described in Example 3 of EP 0242081 A) in DMF (25 ml) was added under cooling (−0° C.) potassium carbonate (930 mg) followed by addition of 2-tert-butyl-4-chloro-1,3,5-triazine (1.15 g, 6.7 mmol). The reaction mixture was stirred at −0° C. for 1.5 h. The reaction mixture was poured into water and extracted with diethyl ether. The organic layer was dried over Na.sub.2SO.sub.4, filtered and concentrated. The crude reaction mixture was then purified by column chromatography using ethyl acetate-hexane (1:3) to give methyl (E)-2-[2-[(4-tert-butyl-1,3,5-triazin-2-yl)oxy]phenyl]-3-methoxy-prop-2-enoate (330 mg, 0.96 mmol, 14%).

Example 4: Methyl (E)-3-methoxy-2-[2-[[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]oxy]phenyl]-prop-2-enoate (Compound 6)

Step 1: 2-Bromo-5-(trifluoromethyl)-1,3,4-thiadiazole

[0233] ##STR00040##

[0234] To a stirred solution of 5-(trifluoromethyl)-1,3,4-thiadiazol-2-amine (5.0 g, 29.5 mmol) in aqueous HBr was added a solution of sodium nitrite (4.48 g, 64.97 mmol) in 125 ml water dropwise at 0° C. during 2 h and stirred for another 2 h. The reaction was diluted with ethyl acetate and brine. The ethyl acetate layer was separated and the aqueous part was washed twice with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated. The crude compound was then purified by flash chromatography using 15% ethyl acetate/hexane to give 2-bromo-5-(trifluoromethyl)-1,3,4-thiadiazole (1.2 g, 5.1 mmol, 17% yield).

Step 2: Methyl (E)-3-methoxy-2-[2-[[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]oxy]phenyl]-prop-2-enoate

[0235] ##STR00041##

[0236] To a stirred solution of 2-bromo-5-(trifluoromethyl)-1,3,4-thiadiazole (710 mg, 3.41 mmol) in 10 ml DMF methyl (E)-2-(2-hydroxyphenyl)-3-methoxy-prop-2-enoate (1.19 g, 5.12 mmol; prepared as described in Example 3 of EP 0242081 A) was added followed by potassium carbonate. The reaction mixture turned brownish. TLC showed complete consumption of starting material after 3 days. The reaction was partitioned between ethyl acetate (50 ml) and water (50 ml). The organic layer was washed subsequently with water (20 ml) and brine (20 ml). The organic layer was dried over Na.sub.2SO.sub.4, filtered and concentrated. The crude reaction mixture was then purified by column chromatography using 20-30% ethyl acetate-hexane to give methyl (E)-3-methoxy-2-[2-[[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]oxy]phenyl]-prop-2-enoate (1.1 g, 3.0 mmol, 88% yield).

Example 5: Methyl (E)-2-[2-[(3-tert-butyl-1,2,4-thiadiazol-5-yl)oxy]phenyl]-3-methoxy-prop-2-enoate (Compound 7)

Step 1: 3-tert-Butyl-5-chloro-1,2,4-thiadiazole

[0237] ##STR00042##

[0238] To a stirred solution of the HCl salt of 2,2-dimethylpropanamidine (1.6 g, 11.8 mmol) in dichloromethane (30 ml) at −15° C. was added trichloromethyl thiohypochlorite (2.0 g, 10.8 mmol) and aqueous sodium hydroxide solution (2.36 g, 59 mmol; dissolved in 12 ml water) slowly. After addition, the temperature of the reaction mixture was slowly raised to room temperature and stirring was continued for 3 h. The reaction mixture was diluted with dichloromethane and washed with water (50 ml×3). The combined organic layer was dried over Na.sub.2SO.sub.4, filtered and concentrated under reduced pressure to give 3-tert-butyl-5-chloro-1,2,4-thiadiazole (1.7 g, 9.6 mmol, 89% yield).

Step 2: 3-tert-Butyl-5-methylsulfonyl-1,2,4-thiadiazole

[0239] ##STR00043##

[0240] To a stirred solution of 3-tert-butyl-5-chloro-1,2,4-thiadiazole (260 mg, 1.47 mmol) in ethylene glycol mono ethyl ether (2 ml) was added at room temperature sodium methanesulfinate (150 mg, 1.47 mmol). After the addition the temperature of the reaction mixture was slowly raised to 100° C. and stirring was continued for 1 h. The reaction was monitored by TLC and after the completion of the reaction the mixture was allowed to cool down to room temperature. The reaction mixture was partitioned between water (5 ml) and CH.sub.2Cl.sub.2 (10 ml). The organic layer was dried over Na.sub.2SO.sub.4, filtered and concentrated under reduced pressure to give the crude material. The crude material was purified by column chromatography using 15-20% ethyl acetate/hexane as an eluent to afford 3-tert-butyl-5-methylsulfonyl-1,2,4-thiadiazole (325 mg, 1.48 mmol, quantitative yield).

Step 3: Methyl (E)-2-[2-[(3-tert-butyl-1,2,4-thiadiazol-5-yl)oxy]phenyl]-3-methoxy-prop-2-enoate

[0241] ##STR00044##

[0242] To a stirred solution of methyl (E)-2-(2-hydroxyphenyl)-3-methoxy-prop-2-enoate (100 mg, 0.48 mmol; prepared as described in Example 3 of EP 0242081) in dry DMF (2 ml) were added 3-tert-butyl-5-methylsulfonyl-1,2,4-thiadiazole (127 mg, 0.57 mmol) and K.sub.2CO.sub.3 (100 mg, 0.72 mmol) at room temperature and stirring was continued for 17 h. The reaction was monitored by TLC and after completion of the reaction the mixture was partitioned between ethyl acetate (10 ml) and brine (10 ml). The organic layer was dried over Na.sub.2SO.sub.4, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography using 15-20% ethyl acetate/hexane as an eluent to give methyl (E)-2-[2-[(3-tert-butyl-1,2,4-thiadiazol-5-yl)oxy]phenyl]-3-methoxy-prop-2-enoate (90 mg; 0.26 mmol 54% yield).

Example 6: Methyl (E)-2-[2-[[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]-3-methoxy-prop-2-enoate (Compound 8)

Step 1: Methyl (E)-2-[2-[[6-chloro-4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]-3-methoxy-prop-2-enoate

[0243] ##STR00045##

[0244] To a solution of 2-chloro-6-fluoro-4-(trifluoromethyl)pyridine (184 mg, 1.1 equiv., 0.924 mmol) in DMF (5 ml) at room temperature was added methyl (E)-2-(2-hydroxyphenyl)-3-methoxy-prop-2-enoate (175 mg, 0.84 mmol; prepared as described in Example 3 of EP 0242081 A) and K.sub.2CO.sub.3 (174 mg, 1.5 equiv., 1.26 mmol). The mixture was stirred at room temperature for 16 h. The mixture was partitioned between diethyl ether and water. The aqueous layer was extracted twice with ether. The combined organic layers were washed with water and brine, dried with MgSO.sub.4, filtered and concentrated under reduced pressure. Column chromatography cyclohexane 100% to cyclohexane/ethyl acetate (80:20) gave methyl (E)-2-[2-[[6-chloro-4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]-3-methoxy-prop-2-enoate (170 mg, 0.439 mmol, 52% yield).

Step 2: Methyl (E)-2-[2-[[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]-3-methoxy-prop-2-enoate

[0245] ##STR00046##

[0246] To a solution of (E)-2-[2-[[6-chloro-4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]-3-methoxy-prop-2-enoate (235 mg, 0.606 mmol) in methanol (5 ml) was added palladium on activated carbon (10%) (118 mg, 1.1041 mmol) and ammonium formate (77 mg, 2 equiv., 1.21 mmol). The mixture was heated at 60° C. for 3 h, then cooled to room temperature, filtered through celite and concentrated under reduced pressure. The residue was partitioned between water and ethyl acetate. The aqueous layer was extracted with ethyl acetate. The combined organic layers were dried and concentrated. Column chromatography 100% cyclohexane to 40% cyclohexane/ethyl acetate (60:40) gave methyl (E)-2-[2-[[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]-3-methoxy-prop-2-enoate (141 mg, 0.399 mmol, 66% yield).

Example 7: methyl (E)-3-methoxy-2-[2-[6-(trifluoromethyl)pyrimidin-4-yl]oxyphenyl]prop-2-enoate (Compound 11)

[0247] ##STR00047##

[0248] To a solution of 4-chloro-6-(trifluoromethyl)pyrimidine (142 mg 0.78 mmol) in DMF (2 ml) at room temperature was added methyl (E)-2-(2-hydroxyphenyl)-3-methoxy-prop-2-enoate (162 mg, 0.78 mmol; prepared as described in Example 3 of EP 0242081 A) and K.sub.2CO.sub.3 (215 mg 1.5561 mmol). The mixture was stirred at room temperature for 48 h. The mixture was partitioned between diethyl ether and water. The aqueous layer was extracted with ether (×2). The combined organic layers were washed with water and brine, dried with MgSO.sub.4, filtered and concentrated under reduced pressure. Column chromatography cyclohexane 100% to Cyclohexane-ethyl acetate (80:20) followed by a second column with dichloromethane to dichloromethane ethyl acetate (90:10) gave methyl (E)-3-methoxy-2-[2-[6-(trifluoromethyl)pyrimidin-4-yl]oxyphenyl]prop-2-enoate (74.6 mg, 0.211 mmol, 27% Yield).

Example 8: Methyl (E)-3-methoxy-2-[2-[5-(trifluoromethyl)thiazol-2-yl]oxphenyl]prop-2-enoate (Compound 13)

Step 1: 2-Bromo-5-(trifluoromethyl)thiazole

[0249] ##STR00048##

[0250] To a stirred and degassed solution of 5-(trifluoromethyl)thiazol-2-amine (590 mg, 3.8 mmol) in CH.sub.2Cl.sub.2 (5 ml), Cu(II)Br (867 mg, 3.88 mmol) and isoamyl nitrite (1.55 ml, 11.64 mmol) were added under argon atmosphere and stirred at room temperature for 1 h. The reaction was monitored by TLC. After completion of the reaction the mixture was quenched with ice water and extracted with pentane. The organic phase was washed with water and brine, dried over sodium sulphate, filtered and concentrated to give the crude compound. The crude compound was then purified by column chromatography using pentane as an eluent to give 2-bromo-5-(trifluoro-methyl)thiazole (˜600 mg, 67% yield).

Step 2: 2-(2-Iodophenoxy)-5-(trifluoromethyl)thiazole

[0251] ##STR00049##

[0252] To a stirred solution of 2-bromo-5-(trifluoro-methyl)thiazole (1.0 g, 4.2 mmol) and 2-iodophenol (1.0 g, 4.62 mmol) in NMP (10 ml) was added 052003 (2.05 g, 6.3 mmol) at room temperature and the reaction mixture was stirred for 4 h. The reaction was monitored by TLC. After completion of the reaction the mixture was quenched with ice water and extracted with ethyl acetate. The ethyl acetate layer was washed with water, brine, dried over sodium sulphate, filtered and concentrated to give a crude product. The crude product was purified by column chromatography to give 2-(2-iodophenoxy)-5-(trifluoromethyl)thiazole (770 mg, 2.07 mmol, 49% yield).

Step 3: Methyl (Z)-2-iodo-3-methoxy-prop-2-enoate

[0253] ##STR00050##

[0254] To a stirred solution of methyl (E)-3-methoxyprop-2-enoate (10.0 g, 86.2 mmol) in CH.sub.2Cl.sub.2 (170 ml), NIS (23.27 g, 103.4 mmol) and AcOH (10.34 g, 172.41 mmol) were added at 0° C. The reaction mixture was stirred at room temperature for 24 h. Then triethylamine (26.17 g, 258.6 mmol) was added and the resulting mixture was stirred for another 12 h at room temperature. The reaction mixture was then partitioned between CH.sub.2Cl.sub.2 (200 ml) and water (200 ml) and the aqueous layer was extracted with CH.sub.2Cl.sub.2. The combined organic layers were washed with saturated NaCl solution, dried over sodium sulphate, filtered and concentrated. The residue was purified by column chromatography on silica gel using 10% ethyl acetate-hexane as eluent to afford methyl (Z)-2-iodo-3-methoxy-prop enoate (11.0 g, 45.5 mmol, 53% yield).

Step 4: Methyl (E)-3-methoxy-2-[2-[5-(trifluoromethyl)thiazol-2-yl]oxyphenyl]prop-2-enoate

[0255] ##STR00051##

[0256] A) To a stirred suspension of Zn/Ag (1.35 g) in THF (7 ml), TMSCl (0.11 ml) was added at room temperature and the mixture was stirred at room temperature for 30 minutes. A degassed solution of TMEDA (0.96 g, 8.2 mmol) and methyl (Z)-2-iodo-3-methoxy-prop-2-enoate (2.0 g, 8.2 mmol) in THF (3 ml) was added and the resulting mixture was stirred at room temperature for 7 h. THF solution was directly used for the cross-coupling reaction.

[0257] B) To a stirred solution of 2-(2-iodophenoxy)-5-(trifluoromethyl)thiazole (400 mg, 1.07 mmol) in THF (3 ml) which was degassed with argon, Pd(PPh.sub.3).sub.4 (62 mg, 0.054 mmol) and the Zink reagent in THF (7 ml) were added. The reaction mixture was stirred at 65° C. for 16 h. After completion of the reaction, the mixture was cooled to room temperature and quenched with saturated aqueous ammonium chloride solution, extracted with ethyl acetate, washed with brine, dried over sodium sulphate, filtered and concentrated to give the crude compound. The crude compound was purified by column chromatography using ethyl acetate-hexane (10-12%) to give methyl (E)-3-methoxy-2-[2-[5-(trifluoromethyl)thiazol-2-yl]oxyphenyl]prop-2-enoate (240 mg, 0.67 mmol 63% yield).

Example 9: Methyl (E)-3-methoxy-2-[2-[[3-(trifluoromethyl)-2-pyridyl]oxymethyl]phenyl]prop-2-enoate (Compound 19)

Step 1: 2-[(2-Iodophenyl)methoxy]-3-(trifluoromethyl)pyridine

[0258] ##STR00052##

[0259] To a solution of (2-iodophenyl)methanol (3.5 g, 15 mmol) in THF (1.7 ml) was added at room temperature sodium hydride (720 mg, 1.2 equiv., 18 mmol, 60%). The mixture was stirred at room temperature for 1 h. Then 2-chloro-3-(trifluoromethyl)pyridine (3.3 g, 1.2 equiv., 18 mmol) was added and the mixture was heated at reflux for 72 h. The mixture was cooled to room temperature and water was added. The mixture was extracted three times with ethyl acetate. The combined organic extracts were washed with brine and dried with MgSO.sub.4, filtered and then concentrated under reduced pressure. Purification by column chromatography with gradient elution 100% cyclohexane to cyclohexane/ethyl acetate (80:20) gave 2-[(2-iodophenyl)-methoxy]-3-(trifluoromethyl)pyridine (4.41 g, 11.6 mmol, 78% yield)

Step 2: Methyl (E)-3-methoxy-2-[2-[[3-(trifluoromethyl)-2-pyridyl]oxymethyl]phenyl]prop-2-enoate

[0260] ##STR00053##

[0261] A) To a suspension of activated zinc dust (1.35 g, 20.1 mmol) in THF (4 ml) was added chloro-trimethylsilane (100 μl, 0.772 mmol). The mixture was stirred for 20 min before the addition of a solution of methyl (Z)-2-iodo-3-methoxy-prop-2-enoate (2 g, 8.26 mmol) and N,N,N′,N′-tetramethylethane-1,2-diamine (1.24 mL, 8.2 mmol) dropwise. The mixture was stirred for 3 h and then allowed to settle. The solution of iodo-[(Z)-2-methoxy-1-methoxycarbonyl-vinyl]zinc; N,N,N′,N′-tetramethylethane-1,2-diamine was used in the next step.

[0262] B) Iodo-[(Z)-2-methoxy-1-methoxycarbonyl-vinyl]zinc; N,N,N′,N′-tetramethylethane-1,2-diamine (8.2 mmol, 8.2 mmol) was added to a solution of 2-[(2-iodophenyl)methoxy]-3-(trifluoromethyl)pyridine (2.2 g, 5.8 mmol) and Pd(PPh.sub.3).sub.4 (50 mg, 0.05 equiv., 0.29 mmol) in THF (5 ml). The mixture was heated to 65° C. for 4 h. The mixture was quenched by addition of saturated aqueous NH.sub.4Cl solution. The mixture was extracted with ethyl acetate. The organic layer washed with brine, dried with MgSO.sub.4, filtered and concentrated under reduced pressure. Column chromatography 100% cyclohexane to cyclohexane/ethyl acetate (60:40) gave methyl (E)-3-methoxy-2-[2-[[3-(trifluoromethyl)-2-pyridyl]oxymethyl]phenyl]prop-2-enoate (1.24 g, 3.38 mmol, 58% yield).

Example 10: Methyl (E)-3-methoxy-2-[2-[[3-(trifluoromethyl)pyrazin-2-yl]oxymethyl]phenyl]prop-2-enoate (Compound 20)

[0263] ##STR00054##

[0264] To a suspension of 3-(trifluoromethyl)pyrazin-2-ol (100 mg, 0.609 mmol) in benzene (5 ml, 55.4 mmol) was added Ag.sub.2CO.sub.3 (203 mg, 1.2 equiv., 0.731 mmol) and methyl (E)-2-[2-(bromomethyl)-phenyl]-3-methoxy-prop-2-enoate (174 mg, 0.609 mmol; prepared as in J. Agric. Food. Chem, 2007, 55, 5697-5700). The mixture was heated at 80° C. for 72 h. The mixture was cooled to room temperature, diluted with dichloromethane, filtered and concentrated. The material was purified by column chromatography cyclohexane 100% to cyclohexane/ethyl acetate (60:40) followed by reversed phase chromatography (27 mg, 0.073 mmol, 12% yield).

[0265] Table 3 & 4 below lists the compounds of the invention 1 to 23 and comparative compounds respectively.

[0266] The table 3 & 4 contains literature references for known compounds and/or physical state or melting point and/or 1H-NMR data. The following abbreviations are used: s=singlet, d=doublet, t=triplet, q=quartet, m=multiplet, m.p.=melting point, ppm=parts per million.

TABLE-US-00003 TABLE 3 methoxyacrylate compounds: compounds 1 to 23 (of the invention) Literature Compound references/ no. CAS m.p. [° C.] 1H-NMR [ppm] 1 WO 9518789 Table 1, compound No. 1.24 171276-46- 3 [00055] 76-78 In CDCl.sub.3: 1.98 (s, 3H), 2.03 (s, 3H), 3.68 (s, 3H), 3.82 (s, 3H), 3.92 (s, 3H), 5.10 (s, 2H), 7.12-7.18 (m, 1H), 7.27-7.37 (m, 2H), 7.43- 7.49 (m, 1H), 7.58 (s, 1H). 2 WO 9505368 Table 1, compound No. 8 163619-68- 9 [00056] gum In CDCl.sub.3: 1.41 (s, 9H), 3.67 (s, 3H), 3.83 (s, 1H), 7.27-7.35 (m, 2H), 7.38-7.43 (m, 1H), 7.56-7.60 (m, 1H), 7.61 (s, 1H) 3 [00057] gum In CDCl.sub.3: 3.58 (s, 3H), 3.63 (s, 3H), 4.52 (q, 2H), 7.1-7.5 (m, 4H), 7.42 (s, 1H), 7.89 (s, 1H), 8,00 (s, 1H). 4 [00058] 75-77 In CDCl.sub.3: 1.01 (t, 3H), 2.02 (s, 3H), 2.68 (q, 2H), 3.71 (s, 3H), 3.86 (s, 3H), 3.98 (s, 3H), 5.12 (s, 2H), 7.15-7.22 (m, 1H), 7.30-7.28 (m, 2H), 7.46-7.52 (m, 1H), 7.61 (s, 1H) 5 [00059] 69-71 In CDCl.sub.3: 1.35 (s, 9H), 3.58 (s, 3H), 3.72 (s, 3H), 7.22-7.42 (m, 4H), 7.48 (s, 1H), 8.81 (s, 1H). 6 GB 2193495A Table 1, compound No. 115 115314-10- 8 [00060] 45-46 3.64 (s, 3H), 3.77 (s, 3H), 7.29-7.35 (m, 3H), 7.35-7.48 (m, 1H), 7.54 (s, 1H) 7 WO 9505368 Table 5, compound No. 8 163619-69- 0 [00061] 64-66 In CDCl.sub.3: 1.36 (s, 9H), 3.58 (s, 3H), 3.70 (s, 3H), 7.29-7.40 (m, 4H), 7.54 (s, 1H). 8 EP 242081 Table 1, compound No. 11 114077-75- 7 [00062] 78-80 In CDCl3: 3.55 (s, 3H), 3.70 (s, 3H), 6.99 (d, 1H), 7.14 (d, 1H), 7.18 (d, 1H), 7.23-7.28 (m, 1H), 7.31-7.40 (m, 2H), 7.42 (s, 1H), 8.32 (d, 1H) 9 [00063] gum In CDCl.sub.3: 1.32 (s, 9H), 3.62 (s, 3H), 3.77 (s, 3H), 6.83 (s, 1H), 7.1-7.5 (m, 4H), 7.52 (s, 1H), 8.79 (s, 1H). 10 WO 9505368, example 5 Table 9, compound No. 8 163619-70- 3 [00064] 103-105 In CDCl.sub.3: 1.30 (s, 9H), 3.63 (s, 3H), 3.76 (s, 3H), 7.27-7.45 (m, 4H), 7.54 (s, 1H). 11 [00065] 102-104 In CDCl.sub.3: 3.59 (s, 3H), 3.72 (s, 3H), 7.09 (s, 1H), 7.19 (d, 1H), 7.31-7.44 (m, 3H), 7.45 (s, 1H), 8.88 (s, 1H). 12 WO 9007493 Table, compound No. 116 130923-57- 8 [00066] gum In CDCl.sub.3: 1.05 (s, 3H), 1.07 (s, 3H), 1.79 (s, 3H), 2.5 (m, 1H), 3.68 (s, 3H), 3.80 (s, 3H), 4.98 (s, 2H), 7.10-7.16 (m, 1H), 7.24-7.36 (m, 2H), 7.43-7.50 (m, 1H), 7.56 (s, 1H). 13 [00067] gum In CDCl.sub.3: 3.62 (s, 3H), 3.74 (s, 3H), 7.28-7.36 (m, 3H), 7.37-7.42 (m, 1H), 7.51-7.53 (m, 2H). 14 [00068] gum In CDCl.sub.3: 1.30 (s, 9H), 3.53 (s, 3H), 3.68 (s, 3H), 6.98 (d, 1H), 7.2-7.4 (m, 4H), 7.42 (s, 1H), 8.40 (d, 1H). 15 WO 9218487 Example 5 Table 1, compound No. 260 145945-47- 7 [00069] 83-85 In CDCl.sub.3: 2.35 (s, 3H), 3.69 (s, 3H), 3.82 (s, 3H), 5.21 (s, 2H), 7.12-7.58 (m, 5 H), 7.62 (s, 1H), 8.13 (s, 1H), 8.74 (d, 1H). 16 [00070] gum 17 [00071] 65-66 In CDCl.sub.3: 3.6 (s, 3H), 3.7 (s, 3H), 7.15 (s, 1H), 7.2-7.5 (m, 4 H), 7.5 (s, 1H), 8.9 (s, 1H). 18 WO 9218487 Table 1, compound No. 270 145945-57- 9 [00072] gum In CDCl.sub.3: 2.32 (s, 3H), 3.64 (s, 3H), 3.82 (s, 3H),5.26 (s, 2H),7.19-7.549 (m, 4H),7.63 (s, 1H), 8.23 (s, 1H), 8.33 (s, 1H). 19 [00073] gum In CDCl.sub.3: 3.71 (s, 3H), 3.84 (s, 3H), 5.42 (s, 2H), 6.92-7.01 (m, 1H), 7.15-7.20 (m, 1H), 7.31-7.41 (m, 2H), 7.62 (s, 1H), 7.60-7.68 (m, 1H), 7.86-7.90 (m, 1H), 8.28-8.33 (m, 1H). 20 [00074] 81-83 In CDCl.sub.3: 3.71 (s, 3H), 3.86 (s, 3H), 5.43 (s, 2H), 7.18-7.23 (m, 1H), 7.33-7.41 (m, 2H), 7.58-7.62 (m, 1H), 7.63 (s, 1H), 8.22 (d, 1H), 8.31 (d, 1H). 21 [00075] amorphous 22 Pesticide Science 1999, 55(2), 197- 198. 222291-33- 0 [00076] 69-71 23 [00077] gum In CDCl.sub.3: 3.70 (s, 3H), 3.85 (s, 3H), 5.30 (s, 2H), 7.10-7.20 (m, 1H), 7.30-7.40 (m, 3H), 7.50-7.60 (m, 1H), 7.66 (s, 1H).

TABLE-US-00004 TABLE 4 methoxyacrylate compounds: comparative compounds A to AD Com- pound Literature m.p. no. references/CAS [° C.] 1H-NMR [ppm] A CSAA383699 EP 382375 131860-33-8 Azoxystrobin [00078] B WO 9521153 171276-50-9 [00079] 36-38 C WO 2000040537 229977-93-9 Fluacrypyrim [00080] D GB 2193495 115314-13-1 [00081] solid E EP 278595 117428-19-0 [00082] gum F EP 373775 131376-48-2 [00083] solid G WO 9218487 145945-43-3 [00084] 87-88 H WO 9218487 145945-41-1 [00085] gum I [00086] 83-85 J [00087] gum K WO 9505368 163619-62-3 [00088] gum L [00089] gum M WO 9505368 163619-74-7 [00090] gum N [00091] gum O [00092] gum P [00093] gum Q EP 414153 134725-65-8 [00094] 92-93 R EP 936213 238410-11-2 Enoxastrobin [00095] S WO 2005080344 862588-11-2 Pyraoxystrobin [00096] T WO 2005044813 850881-70-8 Coumoxystrobin [00097] U WO 2010139271 1257598-43-8 Pyriminostrobin [00098] V Journal of the American Chemical Society 2012, 134(27), 11168-11176. 1384120-13-1 [00099] 115-118 W Journal of the American Chemical Society 2012, 134(27), 11168-11176. 1384120-10-8 [00100] 110-112 X [00101] 122-124 In CDCl3: 3.70 (s, 3H), 3.84 (s, 3H), 5.43 (broad s, 2H), 7.13- 7.20 (m, 1H), 7.31-7.38 (m, 2H), 7.55-7.61 (m, 1H), 7.61 (s, 1H), 8.23 (d, 1H), 8.26 (d, 1H). Y [00102] 113-115 In CDCl3: 1.29 (s, 9H), 3.65 (s, 3H), 3.76 (s, 3H), 7.32-7.43 (m, 3H), 7.47-7.52 (m, 1H), 7.41 (s, 1H). Z [00103] 97-99 In DMSO: 0.82 (t, 3H), 1.15 (d, 3H), 1.43-1.62 (, 2H), 2-62-2.72 (m, 1H), 3.53 (s, 3H), 3.76 (s, 3H), 7.28-7.38 (m, 2H), 7.35 (t, 1H), 7.52 (d, 1H), 7.66 (s, 1H). AA [00104] gum In CDCl.sub.3: 1.30 (s, 9H), 3.61 (s, 3H), 3.76 (s, 3H), 6.84 (s, 1H), 7.21-7.37 (m, 4H), 7.52 (s, 1H). AB [00105] gum AC EP 278595 117428-22-5 Picoxystrobin [00106] AD [00107] 92-94 In CDCl.sub.3: 1.26 (t, 3H), 2.71 (q, 2H), 3.66 (s, 3H), 3.77 (s, 3H), 7.33-7.48 (m, 4H), 7.44 (s, 1H).

BIOLOGY EXAMPLES

Example B1: Aedes aegypti (Yellow Fever Mosquito)

[0267] The individual wells of a twelve (12) well tissue culture plates were treated with 100 μl of an ethanol solution containing a test compound at 20 ppm concentration. Once the deposits were dry, five non-blood fed adult female Aedes aegypti (between two to five days old) were added to each well, and sustained with a 10% sucrose solution in a cotton wool plug. Assessment of the knockdown after 1 hour, and mortality after 48 hours was carried out.

[0268] In case of multiple tests, the mean value is reported. Results for the compounds of the invention and comparative compounds are shown in Table B1.

Example B2: Anopheles stephensi (Indian Malaria Mosquito)

[0269] The individual wells of a twelve (12) well tissue culture plates were treated with 100 μl of an ethanol solution containing a test compound at 20 ppm concentration. Once the deposits were dry, five non-blood fed adult female Anopheles stephensi (beween two to five days old) were added to each well, and sustained with a 10% sucrose solution in a cotton wool plug. Assessment of the knockdown after 1 hour, and mortality after 48 hours was carried out.

[0270] In case of multiple tests, the mean value is reported. Results for the compounds of the invention and comparative compounds are shown in Table B2.

Example B3: Aedes aegypti or Anopheles stephensi

[0271] The individual wells of six (6) well tissue culture plates were treated with 250 μl of an ethanol solution containing a test compound at a defined concentration. Once the deposits were dry, ten non-blood fed adult female Aedes aegypti or Anopheles stephensi (each between two to five day old) were added to each well, and sustained with a 10% sucrose solution in a cotton wool plug. Assessment of the mortality was carried out at 48 hours.

[0272] Each treatment was replicated twice, with the mean mortality recorded.

[0273] Results for certain compounds of the invention and comparative compounds are shown in Table B3.

Example B4: Cross Resistance Studies

[0274] The Individual wells of six (6) well tissue culture plates were treated with 250 μl of an ethanol solution containing a test compound at a defined concentrations. Once the deposits were dry, ten non-blood fed adult female mosquitoes from strains with characterised insecticide resistance mechanisms were added to each well, and sustained with a 10% sucrose solution in a cotton wool plug. In each study, a set of plates were infested with a known insecticide susceptible strain of mosquitoes from the same genera as the resistant strains.

[0275] Assessment of the knockdown after 60 minutes and mortality after 24 hours was carried out. Each treatment was replicated a minimum of four times, with the mean knockdown or mortality recorded.

[0276] A comparison of the knockdown and mortality of the resistant strain of mosquitoes was made to that of the susceptible to identify evidence of cross resistance. Results are shown in Table B4.

Example B5: Bottle Based Cross Resistance Study

[0277] Based on the “CDC bottle assay” (described at http://www.cdc.gov/malaria/resources/pdf/fsp/ir_manual/ir_cdc_bioassay_en.pdf) 1 ml of ethanol containing a test compound at a defined concentration was added to a 250 ml glass bottle and the bottles were placed on a rolling table to coat the inner surfaces as the solvent evaporated. Once dry, twenty five non-blood fed adult female mosquitoes of the appropriate species and strains (each three day old) were aspirated from the stock culture and gently blown into the exposure bottles. The lid of the bottle was replaced and the bottle placed upright out of direct sun light under standard culture conditions, nominally 28 C and 60-80% relative humidity.

[0278] A stopwatch was started, and the assessment of the knock-down were made after 15 minutes and 60 minutes. A mosquito was said to be knocked down if it was unable to stand, following the CDC definition. The bottles were replaced in an upright position when not being assessed.

[0279] After one hour the mosquitoes were carefully removed from the bottle with an aspirator and placed in a recovery cup. The mosquitoes were supplied with a 10% sucrose solution on a cotton wool bung, and stored under culture conditions. Assessments of the mortality were made after 24 hours.

[0280] Each treatment was replicated a minimum of four times, with the mean knockdown or mortality recorded. In each study, a set of bottles was infested with a known insecticide susceptible strain of mosquitoes from the same genera as the resistant strains. Results are shown in Tables B5.

Example B6: Evaluation of Residual Insecticidal Formulations

[0281] Experimental surfaces were sprayed with diluted residual insecticide formulation comprising a compound of the invention using an automated hydraulic sprayer fitted with an 8003 flat fan nozzle—corresponding to a coverage of 500 mg of compound per m2. Also applied was a lambda-cyhalothrin formulation (DEMAND 10 CS) such that there was 25 mg of lambda-cyhalothrin Al per m2. The pirimiphos-methyl formulation (ACETELLIC 300CS) was applied so that there was 1000 mg of pirimiphos-methyl Al per m2 (Table B6b).

[0282] The treated surfaces were stored in a controlled environment room at 28° C., ambient humidity and under low light conditions for 1 (one) week.

[0283] Three to five day old non-blood fed adult mosquitoes were taken from the culture and lightly anaesthetised with carbon dioxide. Ten females were selected and placed in a 250 ml plastic cup, retained with a net lid, provided with a 10% sucrose solution soaked in a cotton wool bung and held under culturing environmental conditions.

[0284] After twenty four hours, treated tiles, treated 7 days previously with a formulation, were removed from storage. A cup of the pre-selected mosquitoes were again lightly anaesthetised with carbon dioxide and transferred from the holding cup to the base of a 9 cm plastic Petri dish. The treated side of the relevant surface was placed over the Petri dish and held in place with an elastic band. Once the mosquitoes had recovered from the anaesthetic, ca. 1 minute, the treated surface attached to the Petri dish was placed on a holding rack, such that treated side was at an angle of 60° to the horizontal.

[0285] After one hour an assessment of mosquito knockdown was made. A mosquito was said to be knocked down if it was unable to right itself once it had fallen over. The mosquitoes were lightly anaesthetised again, and removed from the Petri dish exposure chamber and returned to the holding cups. The mosquitoes were supplied with a 10% sucrose solution soaked in a cotton wool bung and held under culturing environmental conditions. An assessment of mortality was made 24 hours after exposure. A mosquito was said to be dead if it is unable to right itself once it has fallen over. Results are shown in Tables B6.

Example B7: Evaluation of Insecticide Impregnated Polymer Surfaces

[0286] Preparation of polymeric sheets: Certain methoxyacrylate were Impregnated into three polymers: LDPE (low density polyethylene), HDPE (high density polyethylene) and PP (polypropylene) in different concentrations by mixing the respective polymer with a compound at high temperatures and the resultant polymeric material were then mould into thin discs or plaques.

[0287] Twenty four hours prior to the relevant assessment intervals, three to five day old non-blood fed adult mosquitoes were taken from the culture and lightly anaesthetised with carbon dioxide. Ten females were selected and placed in a 250 ml plastic cup, retained with a net lid, provided with a 10% sucrose solution soaked in a cotton wool bung and held under culturing environmental conditions.

[0288] After twenty four hours, impregnated polymer sheets (measuring about 150 mm in diameter and about 0.1 mm in thickness) were removed from storage and wrapped around the glazed side of an 11 cm ceramic tile and held in place with an elastic band. The age of the polymer sheets used are indicated in the tables below. A cup of the pre-selected mosquitoes were again lightly anaesthetised with carbon dioxide and transferred from the holding cup to the base of a 9 cm plastic Petri dish. The relevant impregnated polymer sheet was placed over the Petri dish and held in place with an elastic band. Once the mosquitoes had recovered from the anaesthetic, ca. 1 minute, the impregnated polymer sheet was placed on a holding rack, such that treated side was at an angle of 60° to the horizontal.

[0289] After one hour an assessment of mosquito knockdown was made. A mosquito was said to be knocked down if it was unable to right itself once it had fallen over. The mosquitoes were lightly anaesthetised again, and removed from the Petri dish exposure chamber and returned to the holding cups. The mosquitoes were supplied with a 10% sucrose solution soaked in a cotton wool bung and held under culturing environmental conditions. An assessment of mortality was made 24 hours after exposure. A mosquito was said to be dead if it is unable to right itself once it had fallen over. Results are shown in Tables B7.

TABLE-US-00005 TABLE B1 Compound no. Knockdown (%) Mortality (%) 1 50 90 2 0 80 3 0 100 4 100 100 5 100 100 6 100 100 7 100 100 8 67 100 9 0 80 10 80 93 11 100 100 12 100 100 13 100 100 14 0 40 15 50 100 16 0 80 17 100 100 18 0 40 19 20 100 20 100 100 21 50 90 22 100 100 23 100 100 A 0 0 B 0 0 C 0 0 D 0 0 E 0 0 F 0 60 G 0 0 H 0 0 I 0 40 J 0 0 K 0 0 L 0 0 M 0 0 N 0 0 O 0 0 P 0 0 Q 0 0 R 0 0 S 0 0 T 0 0 U 0 0 V 0 0 W 0 0 X 0 0 Y 0 0 Z 0 0 AA 0 0 AB 60 100 AC 0 40 AD 0 0 Blank 0 0 DDT (10 ppm) 35 90 Lambda- 92 100 cyhalothrin (2 ppm)

TABLE-US-00006 TABLE B2 Compound no. Knockdown (%) Mortality (%) 1 40 100 2 40 100 3 100 100 4 80 100 5 100 100 6 100 100 7 67 100 8 100 100 9 100 100 10 93 100 11 80 100 12 100 100 13 100 100 14 0 100 15 40 100 16 20 100 17 100 100 18 100 100 19 40 100 20 100 100 21 100 100 22 100 100 23 20 100 A NT NT B NT NT C NT NT D NT NT E NT NT F 60 100 G NT NT H NT NT I NT NT J NT NT K NT NT L NT NT M NT NT N NT NT O NT NT P NT NT Q NT NT R NT NT S NT NT T NT NT U NT NT V NT NT W NT NT X NT NT Y NT NT Z NT NT AA NT NT AB 100 100 AC 100 100 AD NT NT Blank 0  0 DDT (10 ppm) 70  80 Lambda- 83 100 cyhalothrin (2 ppm) Notes; NT is not tested

TABLE-US-00007 TABLE B3 Aedes aegypti Anopheles stephensi ppm 5 5 compound 1 74 100 2 90 100 4 78 98 5 85 100 6 66 98 7 78 95 8 100 100 10 47 93 12 43 100 13 78 100 15 70 95 16 20 95 17 5 55 18 70 100 19 75 100 20 70 100 21 85 100 22 100 100 23 60 93 F 30 20 AB 75 80 AC 4 75 ppm 5 5 DDT 85 59 ppm 0.2 0.2 Lambda-cyhalothrin 99 84

TABLE-US-00008 TABLE B4 Knockdown (%) Mortality (%) Compound 4 6 7 10 Permethrin 4 6 7 10 Permethrin concentration/ppm 2.00 2.0 2.50 1.56 2.50 2.00 2.00 2.50 1.56 2.50 An. Gambiae 67 86 100 90 100 95 100 100 100 100 Kisumu sus An. Gambiae 30 78 90 70 100 100 89 100 70 100 Kisumu rdl An. Gambiae 70 84 90 80 5 100 94 85 75 14 Tiassalé An. Arabiensis 0 90 95 90 75 95 100 100 90 100 Moz sus An. Arabiensis 100 100 NT 68 NT 100 100 NT 79 NT Ndjamina Ae. aegypti 45 5 52 55 0 90 63 28 55 45 Caymon Ae. Aegypti 75 95 38 70 91 100 100 100 85 100 New Orleans An. stephensi 95 100 40 0 85 100 100 100 100 100 Notes; NT is not tested

TABLE-US-00009 TABLE B5a Knockdown (%) at 15 mins Knockdown (%) at 60 mins Mortality (%) Compound 4 6 7 10 Permethrin 4 6 7 10 Permethrin 4 6 7 10 Permethrin concentration/ppm 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 An. Gambiae 48 100 100 71 100 100 100 100 100 100 100 100 99 48 100 Kisumu sus An. Gambiae 17 93 70 9 50 96 98 97 24 99 77 91 95 5 85 Tiassalé An. stephensi 10 83 37 57 97 100 100 100 100 100 80 100 100 30 100

TABLE-US-00010 TABLE B5b Mortality (%) Compound 8 13 22 Permethrin concentration/ppm 25 25 25 25 FUMOZ 56 70 68 24 VK7 20 61 96 3 Kisumu sus 61 94 100 99

TABLE-US-00011 TABLE B5c Mortality (%) Compound 7 Permethrin concentration/ppm 25 25 FUMOZ 20 46 VK7 19 4 Kisumu sus 97 100

[0290] Notes on mosquito species used in tables B4 & B5:

TABLE-US-00012 Country of Name Species Origin Phenotype Kisumu Anopheles gambiae Kenya Susceptible Kisumu Rdl Anopheles gambiae Kenya Dieldrin resistant Tiassalé Anopheles gambiae Cote d'lvoire Pyrethroid resistant Moz Anopheles arabiensis Mozambique Susceptible New Orleans Aedes aegypti USA Susceptible Cayman Aedes aegypti Grand Pyrethroid, Cayman carbamate & DDT resistant Ndjamina Anopheles arabiensis Chad Pyrethroid resistant VK7 Anopheles coluzzii Burkina Faso Pyrethroid resistant FUMOZ Anopheles funestus Mozambique Pyrethroid resistant SYN Anopheles stephensi India Susceptible

TABLE-US-00013 TABLE B6a formulation compound Knockdown (%) Mortality (%) 4A 4 70 100 7A 7 77 100 10A 10 3 30 Demand 10CS Lambda-cyhalothrin 100 100 Water control 0 0 Notes: Formulations 4A, 7A and 10A are each aqueous suspension concentrates containing about 10 wt % of active ingredient and also containinging conventional co-formulants in standard amounts, such as a dispersant, antifreeze, preservative, thickener, wetter, emulsier, and water as the carrier.

TABLE-US-00014 TABLE B6b formulation compound Knockdown (%) Mortality (%) 7B 7 67 100 ACTELLIC pirimiphos-methyl 0 100 300CS Water control 0 3 Notes: Formulations 7B is an aqueous suspension concentrates containing about 10 wt % of active ingredient and also containinging conventional co-formulants in standard amounts, such as a dispersant, antifreeze, preservative, thickener, wetter, emulsier, and water as the carrier.

TABLE-US-00015 TABLE B7a age of impregnated polymer 4 to 6 weeks old against Aedes aegypti (knockdown) Al content, knock-down (%) compound wt % LDPE HDPE PP 4 2 63 53 63 6 2 100 87 83 7 2 100 83 67 10 2 23 80 0 17 2 100 NT NT Permethrin 2 100 100 87 Blank n/a 0 0 0

TABLE-US-00016 TABLE B7b age of impregnated polymer 4 to 6 weeks old against Aedes aegypti (mortality) Al content, mortality (%) compound wt % LDPE HDPE PP 6 2 90 17 13 7 2 97 47 23 10 2 97 17 13 Permethrin 2 100 97 80 Blank n/a 0 0 0

TABLE-US-00017 TABLE B7c age of impregnated polymer 4 to 6 weeks old against Anopheles stephensi (knockdown) Al content, knock-down (%) compound wt % LDPE HDPE PP 4 2 87 93 100 6 2 97 87 100 7 2 100 93 93 10 2 87 90 0 Permethrin 2 100 100 100 Blank n/a 0 0 0

TABLE-US-00018 TABLE B7d age of impregnated polymer 4 to 6 weeks old against Anopheles stephensi (mortality) Al content, mortality (%) compound wt % LDPE HDPE PP 4 2 70 60 87 6 2 83 60 57 7 2 97 87 87 10 2 93 73 10 Permethrin 2 100 70 23 Blank n/a 0 0 0

TABLE-US-00019 TABLE B7e age of impregnated polymer 6 to 8 weeks old against Anopheles stephensi (knockdown) Al content, knock-down (%) compound wt % LDPE HDPE PP 4 2 70 77 90 6 2 100 100 90 7 2 87 100 100 10 2 90 20 17 Permethrin 2 100 100 100 Blank n/a 0 0 0

TABLE-US-00020 TABLE B7f age of impregnated polymer 6 to 8 weeks old against Anopheles stephensi (mortality) Al content, mortality (%) compound wt % LDPE HDPE PP 4 2 100 80 100 6 2 77 63 80 7 2 100 87 77 10 2 100 17 93 Permethrin 2 100 97 67 Blank n/a 10 7 13

TABLE-US-00021 TABLE B7g age of impregnated polymer 2 to 4 weeks old against Aedes aegypti (knockdown) Al content, knock-down (%) compound wt % LDPE HDPE PP 5 2 13 33 80 8 2 100 100 n/t 12 2 100 97 100 13 2 100 100 100 22 2 100 93 100 Blank n/a 0 0 0

TABLE-US-00022 TABLE B7h age of impregnated polymer 2 to 4 weeks old against Aedes aegypti (mortality) Al content, mortality (%) compound wt % LDPE HDPE PP 5 2 13 27 40 8 2 100 53 n/t 12 2 100 27 80 13 2 93 73 87 22 2 100 93 100 Blank n/a 0 7 13

TABLE-US-00023 TABLE B7i age of impregnated polymer 6 to 8 weeks old against Aedes aegypti (knockdown) Al content, knock-down (%) compound wt % LDPE HDPE PP 5 2 85 60 70 8 2 100 100 n/t 12 2 95 100 100 13 2 100 100 100 22 2 100 95 100 Blank n/a 0 0 0

TABLE-US-00024 TABLE B7j age of impregnated polymer 6 to 8 weeks old against Aedes aegypti (mortality) Al content, mortality (%) compound wt % LDPE HDPE PP 5 2 95 15 55 8 2 100 75 n/t 12 2 55 75 70 13 2 95 65 35 22 2 100 100 100 Blank n/a 0 10 5

TABLE-US-00025 TABLE B7k age of impregnated polymer 2 to 4 weeks old against Anopheles stephensii (knockdown) Al content, knock-down (%) compound wt % LDPE HDPE PP 5 2 80 100 90 8 2 100 100 n/t 12 2 100 100 100 13 2 100 100 100 22 2 100 100 100 Blank n/a 7 0 0

TABLE-US-00026 TABLE B7l age of impregnated polymer 2 to 4 weeks old against Anopheles stephensii (mortality) Al content, mortality (%) compound wt % LDPE HDPE PP 5 2 87 80 67 8 2 100 100 n/t 12 2 100 97 97 13 2 100 100 100 22 2 93 97 93 Blank n/a 3 10 0

TABLE-US-00027 TABLE B7m age of impregnated polymer 8 to 12 weeks old against Anopheles stephensii (knockdown) Al content, knock-down (%) compound wt % LDPE HDPE PP 5 2 70 50 20 8 2 90 100 n/t 12 2 30 100 100 13 2 100 90 100 22 2 80 90 100 Blank n/a 0 0 0

TABLE-US-00028 TABLE B7n age of impregnated polymer 8 to 12 weeks old against Anopheles stephensii (mortality) Al content, mortality (%) compound wt % LDPE HDPE PP 5 2 100 20 50 8 2 100 80 n/t 12 2 0 30 70 13 2 80 0 10 22 2 100 90 100 Blank n/a 0 0 0