WO1997016067A1

WO1997016067A1 - Compounds for control of whitefly

Info

Publication number: WO1997016067A1
Application number: PCT/GB1996/002622
Authority: WO
Inventors: Bhupinder Pall Singh Khambay; Matthew Robert Cahill
Original assignee: British Technology Group Limited
Priority date: 1995-10-30
Filing date: 1996-10-28
Publication date: 1997-05-09
Also published as: EP0876099A1; NZ320450A; JPH11514369A; BR9611503A; GB9522144D0; KR19990067206A; MX9803382A; ZA969126B; AU7318896A

Abstract

A method of combating a resistant strain of whitefly at a locus infested by the resistant strain of whitefly is provided comprising applying to the locus an amount effective to combat the whitefly of a least one compound of formula (I), in which formula: X is hydrogen or fluorine; Y is CH2, CHF or O and Z is CH2, or Y is CH or CF and Z is CH, Y and Z forming a double bond, or Y is CH2 and Z is CO; R1 is optionally substituted phenyl; R2 is hydrogen and R3 is CF¿3?, isopropyl or cyclopropyl, or R?2 and R3¿ are methyl, or R?2 and R3¿ together form a cyclopropyl ring; and Ar is a phenyl or naphthyl group optionally substituted by one or more halogen, alkoxy, haloalkoxy, methylenedioxy, C¿1?-C6 alkyl or haloalkyl groups.

Description

COMPOUNDS FOR CONTROL OF WHITEFLY

This invention relates to the control of whitefly and is particularly directed to the control of resistant strains of whitefly.

Within the last decade whitefly, in particular tobacco whitefly (Bemisia tabaci. has become a major pest of many crops in many countries. As a pest it causes direct feeding damage, exudes copious honeydew (which is a substrate for fungi), creates harvesting difficulties (especially in cotton) and transmits a large number of plant viruses. It has become established in glasshouse horticulture in continental Europe and poses a threat to agriculture in the UK despite efforts at quarantine. The problem is exacerbated by the dissemination of resistant strains which are highly fecund, have a wider host range and which are resistant to the major groups of insecticides, i.e. organochlorine, organophosphorus, carbamate and pyrethroid insecticides.

There is thus an urgent need for the provision of new methods of whitefly control directed in particular against the resistant whitefly strains. Accordingly the present invention provides a method of combating a resistant strain of whitefly at a locus infested by the resistant strain of whitefly comprising applying to the locus an amount effective to combat the whitefly of at least one compound of formula I.

in which formula X is hydrogen or fluorine;

Y is CH₂, CHF or O and Z is CH₂, or Y is CH or CF and Z is CH, Y and Z forming a double bond, or Y is CH₂ and Z is CO; Rl is optionally substituted phenyl;

R.2 is hydrogen and R^ is CF3, isopropyl or cyclopropyl, or R^ and R-> are methyl, or R2 and R^ together form a cyclopropyl ring; and

-1-

8UBST1TUTE SHEET (RULE 26) Ar is a phenyl or naphthyl group optionally substituted by one or more halogen, alkoxy, haloalkoxy, methylenedioxy, C_j-Cg alkyl or haloalkyl groups.

Preferably Ar in formula I represents a phenyl group, preferably substituted at the para position. Preferred substituents are halogen, particularly chlorine and fluorine and alkoxy, especially ethoxy.

R* is preferably an unsubstituted phenyl group.

Those compounds where X is fluorine are especially preferred.

It will be appreciated that, dependent on the substituents, optically active carbon atoms may be present. It is intended to include optically active as well as racemic forms of such compounds. When Y and Z form a double bond, the compounds preferably have the two carbon-containing substituents in a trans configuration.

A particularly preferred group of compounds according to the invention are those of formula II

in which Ar, X and R* are as defined above and W is hydrogen or fluorine. Compounds of formula II where W is hydrogen are described and claimed in UK Patent No. 2167749. Compounds of formula II where W is fluorine are the subject of co-pending UK Application No. 9219612.0.

A further preferred group of compounds are those of formula III

wherein Ar, X and R* are as defined above, W is hydrogen or fluorine and either R^ is hydrogen and R- represents a cyclopropyl group or R* and R^ each represent a methyl group. Compounds of formula III where W is hydrogen are disclosed in US Patent No. 4975451 and Japanese Patent Publications Nos. 60115545, 60193902 and 60193940. Compounds of formula III where W is fluorine are the subject of co-pending UK Application No. 9308626.2. Preferably X is fluorine. An additional group of preferred compounds are those of formula IV

wherein Ar, X and R* are as defined above, R^ is hydrogen and R^ is CF3 or R^ and R^ are methyl. Such compounds and their preparation are disclosed in Baydar et ai., Pestic. Sci. 1988, 2 247-257, or UK Patent No. 2118167. Also included within the present invention are compounds of formula V

where Ar, X and R are as defmed above and W is hydrogen or, more preferably, fluorine. Compounds of formula V where W is fluorine are novel and may be prepared by the preparation route generally described in co-pending UK Application No. 9308626.2 and exemplified herein.

Also included within the present invention is the use of compounds of formula VI

where Ar, X and R' are as defined above. R^ and R^J are methyl or R^ is hydrogen and R^J is cyclopropyl or R^ and R-* together form a cyclopropyl ring, and W is hydrogen

- or fluorine. Certain of such compounds and their preparation are described in UK Patent No. 2120664.

Although the compounds of formulae I to VI as defined above have been generally proposed for use as insectieidal agents and, for example, UK Patent No. 2167749 mentions activity against whitefly in a list of a very large number of insect orders and individual species, no biological data showing effectiveness against whitefly has been given in the above reference documents. It was therefore suφrising to find that compounds of formula I had generally good activity against whitefly and even more suφrising to find that that good activity was largely maintained against resistant whitefly strains. This maintenance of activity is in clear contrast to the majority ofthe commercially available pyrethroid ester insecticides, and an organochlorine insecticide such as DDT, which, while showing reasonable levels of activity against non-resistant strains, show very much reduced activity against resistant strains. This difference is illustrated in the following examples.

The compounds of formula I to VI as described above can be formulated in many ways for use in combating resistant whitefly. They can therefore be employed in a pesticidal composition comprising a compound of formulae I to VI as an active ingredient together with an inert carrier or diluent.

Suitable diluents include both solid and liquid diluents so as to provide compositions which can be formulated for example as granules, dusts or emulsifiable concentrates. Examples of diluents suitable for the preparation of granular compositions are porous materials such as pumice, gypsum or corn cob grits. Suitable diluents for the preparation of dusts include kaolin, bentonite, kieselguhr or talc. For the preparation of emulsifiable concentrates, various solvents, such as ketones and aromatic solvents, may be employed together with one or more known wetting agents, dispersing agents or emulsifying agents.

Solid compositions especially granules, preferably contain from 0.5 to 15% by weight of active ingredient, while liquid compositions, as applied to the crop, may contain as little as from 0.0001 to 1% by weight of active ingredient. A composition such as a wettable powder however may contain as much as 75% by weight of active ingredient. Dependent on the mode of use, the compositions may conveniently be applied to the locus of whitefly infestation at an application rate of from 1 to 500 g of active ingredient per hectare.

It will be appreciated that the compositions may include a mixture of compounds of formula I and/or other ingredients, including another pesticidal material, eg. an insecticide, acaricide or fungicide, or a synergist.

It is intended that the compositions may be applicable to foliage soil and/or seeds during cultivation of a wide variety of foliage, horticultural and agricultural crops such as maize, sugar beet, potatoes, tobacco and cotton. The compositions are particularly useful in combating resistant strains of

Bemisia tabaci. but are also contemplated for use to combat other resistant whitefly strains such as Trialeurodes vaporariorum and abutilonea.

The following examples illustrate the invention.

A) Preparation of compounds of Formula I . Compounds of Formula I were prepared by the methods referenced in Table 1 below or in accordance with preparative Examples 1 to 5 below in which Examples 1 to 3 relate to the preparation of intermediates and Examples 4 and 5 to compounds in accordance with the invention.

Table 1

Compound No X Z-Y R2 R^J R4 Preparation

1 H CH=CH -CH₂ -CH₂- Cl A

2 F CH=CH -CH₂-CH₂- Cl A 3 H CH=CF -CH₂-CH₂- Cl B

4 F CH=CF -CH₂-CH₂- Cl B

5 H CH=CH -CH₂ -CH₂- EtO A

6 F CH=CH -CH₂- ^■CH₂- EtO A

7 H CH=CF -CH₂-CH₂- EtO B 8 F CH=CF -CH₂-CH₂- EtO B

9 H CH=CF -CH₂- CH₂- F B

10 F CH=CF -CH₂- CH₂- F B

1 1 H CH=CF CH₃ CH₃ Cl E

12 F CH=CF CH₃ CH₃ Cl E 13 H CH=CF CH₃ CH₃ EtO E

14 F CH=CF CH₃ CH₃ EtO E

15 H CH=CF H iPr Cl G

16 F CH=CF H iPr Cl G

17 H CH=CH H -< Cl F 18 H CH=CF H Cl 19 F CH=CF H -< Cl 0 H CH=CF H - < EtO Table 1 (continued)

Compound No X Z-Y R2 R3 R4 Preparation

21 F CH=CF H - < EtO E

22 H CH₂-O CH₃ CH₃ EtO H

23 F CH₂-O CH₃ CH₃ EtO C

24 F CH₂-O -CH₂-CH₂- Cl C

25 F CH₂-O H CF₃ EtO D

26 H CH₂-O H CF₃ EtO D

27 F CH₂-CH₂ CH₃ CH₃ EtO I

Preparations were carried out in accordance with

A UK Patent No. 2167749

B UK Application No. 9219612.0

C Baydar et al. Pestic. Sci. 1988, 21, 247-257

D UK Patent No. 2178739 E UK Application No. 9308626.2

F US Patent No. 4975451

G As shown below

H UK Patent No. 2118167

I UK Patent No. 2120664 In the following Examples. ^C NMR peaks are listed as assigned peaks in the order indicated by the following diagram:

Equivocal assignments are indicated by subscripts, a, b. Peaks not detected above the noise level are indicated by N. Coupling constants to fluorine are given in brackets, and are in Hz.

Example 1

Methvl 4-r4-chlorophenvn-2-fluoro-5-methvlhex-2-enoate

To a stirred mixture of acid-washed zinc powder (2.33 g), copper (I) chloride (0.38 g) and molecular sieve 4A (2.6 g) in dry tetrahydrofuran (36 ml) under nitrogen, 2-(4-chlorophenyl)-3-methylbutanal (2.26 g) was added slowly, followed by acetic anhydride (1 ml). After the mixture had been warmed to 50°. methyl o dichlorofluoroacetate (2.3 g) was added dropwise, and stirring continued for 4 h at 50 . After cooling, the mixture was diluted with diethyl ether (150 ml), filtered through a bed of celite, and the filtrate was concentrated under reduced pressure. The residual oil was chromatographed on silica gel using diethyl ether/hexane (1 :9) to yield methyl 4-(4-chlorophenyl)-2-fluoro-5-methylhex-2-enoate 1.08g 34%.

4-f4-Chloroρhenvn-l-(2-fluoro-5-methvlthex-2-enol

Methyl 4-(4-chlorophenyl)-2-fluoro-5-methylhex-2-enoate prepared as described in Example 1 (1.08 g) in dry diethyl ether (20 ml) was added dropwise to a stirred o suspension of lithium aluminium hydride (0.3 g) in dry diethyl ether at 0 C. Stirring was continued during 40 min, while the mixture warmed to room temperature. -Water (20 ml) was added, and the mixture was extracted with diethyl ether (3 x 20 ml). The combined organic layers were washed with water (3 x 10 ml), dried and evaporated under reduced pressure. The residue was chromatographed on silica using diethyl ether hexane (1 :2) to yield 4-(4-chlorophenyl)-2-fluoro-5-methylhex-2-enol 0.78g 81%.

Example 3

4-f4-chlorophenylV2-fluoro-5-methylhex-2-enyl acetate Acetyl chloride (0.84 ml) was slowly added to a stirred solution of

4-(4-chlorophenyl)-2-fluoro-5-methylhex-2-enol (Example 2) (0.39 g) in benzene (20 ml) o and pyridine (0.17 ml) at 0 C, and stirring was continued for 24 h while the mixture warmed to room temperature. After addition of water (10 ml), the mixture was extracted with diethyl ether (3 x 20 ml) and the combined organic layers were washed with water (3 x 10 ml) and evaporated under reduced pressure. The residue was chromatographed on silica using diethyl ether hexane (1 :9) to yield 4-(4-chlorophenyl)-2-fluoro-5-methylhex- 2-enylacetate (0.4 g, 87%).

Example 4

4-f4-Chloronhenvn-2-fluoro-5-methvl-l-G-phenoxyphenvnhex-2-ene A Grignard reagent, prepared from 3-phenoxyphenyl bromide (0.47 g) in dry tetrahydrofuran (3 ml) and magnesium (34 mg) under nitrogen using iodine as an initiator o at ca 40 C for 50 min, was cooled to room temperature then treated with cuprous bromide o

{ca 20 mg) for 10 min. After cooling to -78 C, a solution of 4-(4-chlorophenyl)- 2-fluoro-5-methylhex-2-enyl acetate (Example 3) (0.14 g) in tetrahydrofuran was added slowly with stirring, then the mixture was allowed to warm to room temperature overnight. The mixture was treated with water (4 ml), then extracted with diethyl ether (3 x 20 ml). The combined organic extracts were washed with water (2 x 10 ml), dried, and evaporated under reduced pressure. The residue was purified by preparative thin layer chromatography (solvent: diethyl ether/hexane; 1 :9) and then preparative high performance liquid chromatography (column: C18; solvent: methanol; flow rate: 3 ml/min) to afford 4-(4-chlorophenyl)-2-fluoro-5-methyl-l-(3-phenoxyphenyl)hex-2-ene (36 mg, 18%). ¹³C NMR spectrum:

142.7, 128.5^a, 129.1^a, 131.6. 47.3(3). 33.5. 20.9,20.2. 109.5(15), 158.0(256), 38.5(29), 138.4. 117.3, 157.5^b, 1 19.1. 129.8, 123.6. 157.0^b, 1 18.9, 129.8, 123.3 Example 5 4-r4-Chlorophenvn-2-fluoro-l-r4-fluoro-3-Dhenoxyphenvn5-methylhex-2-ene

The method of Example 4 was repeated using a Grignard reagent, prepared from 4-fluoro-3-phenoxyphenyl bromide (0.3 g), tetrahydrofuran (2 ml) and magnesium (28 mg) and 4-(4-chlorophenyl)-2-fluoro-5-methylhex-2-enol (Example 3) (0.96 g). The residue after evaporation was purified by preparative thin layer chromatography (solvent: diethyl ether/hexane; 1 :9) to afford 4-(4-chlorophenyl)-2-fluoro-l-(4-fluoro- 3-phenoxyphenyl)-5-methylhex-2-ene (27mg; 19.4%) ¹³C NMR spectrum: 142.7, 128.5^a, 129.0^a, 131.6, 47.3(3), 33.4, 20.9, 20.2, 109.6(15), N, 38.9(29), 136.7(3), 121.8, N, N, 1 17.0(18), 124.8(7), 157.1, 1 17.3, 129.9, 123.3

B) Biological Data

The compounds 1 to 26 identified in Table 1 were tested against susceptible and resistant strains of whitefly (Bemisia tabaci). The susceptible strain "SUD-S" was collected from the Sudan in 1978 by Ciba-Geigy and subsequently laboratory cultured to provide the standard laboratory susceptible strain. The resistant strain "BELZ" was collected from broccoli in Belize in November 1991. It is an example of this "poinsettia" strain of Bemisia tabaci which is the biotype causing control difficulties in American field crops and glasshouses and in European glasshouses at the time of making the present patent application.

The tests were carried out as follows:

Acetone solutions (100 ml) ofthe test compounds were placed in glass vials and evaporated with rotation to deposit a film ofthe compound. Thirty adult whiteflies were placed inside the vial, then after 60 minutes, the treated insects were transferred onto untreated cotton leaf discs which were kept moist on a bed of agar gel. The temperature was maintained at 25 °C and mortality assessed after 48 hours. Three replicates were used at each of 5 to 7 dose levels per compound. LC50 values were calculated by using a computer software package ("Polo-PC" available from LeOra Software, Berkeley, California). The LC50 values are given in ppm (i.e. concentration ofthe acetone solution used) in Table 2 below. Several commercially available pyrethroid esters and one organochlorine insecticide (DDT) are included in the Table for reference.

Table 2

Compound SUD-S LC₅₀ BELZ LC₅₀

1 1.1

2 0.8 6.7

3 2.2 7.7

4 0.67 30

5 0.94

6 0.42 1.1

7 0.35 4.2

8 1.1 2.6

9 1.3 17

10 0.64 3.6

11 80 670

12 0.65 0.95

13 2.6 44

14 0.7 10

15 80

16 23 61

17 1.6 14

18 0.78 90

19 1.1 5.7

20 8.3

21 39.4

22 0.86 3.5

23 0.28 0.3

24 1.6

25 0.24 0.49 Table 7 (continued)

Compound SUD-S LC₅₀ BELZ LC₅0

26 0.82 1.05

27 0.67 1.5 Cypermethrin 9.1 170

Bifenthrin 0.66 1.2

Fenpropathrin 4.3 48

Tefluthrin 1.9 40

Fenfluthrin 2.0 22 Fenvalerate 3.9 83

Flucythrinate 5.9 480

Deltamethrin 0.4 > 1000

Permethrin 9.5 600

DDT 5.9 110

-12- SUBSnTUTE SHEET (RULE 2ζ)

Claims

CLAIMS 1. A method of combating a resistant strain of whitefly at a locus infested by the resistant strain of whitefly comprising applying to the locus an amount effective to combat the whitefly of at least one compound of formula I

in which formula

X is hydrogen or fluorine;

R2 is hydrogen and R³ is CF₃, isopropyl or cyclopropyl, or R^ and R³ are methyl, or R^ and R³ together form a cyclopropyl ring; and

Ar is a phenyl or naphthyl group optionally substituted by one or more halogen, alkoxy, haloalkoxy, methylenedioxy, C_j-Cg alkyl or haloalkyl groups.

2. A method according to claim 1 wherein Ar represents a para substituted phenyl group.

3. A method according to claim 1 or 2 wherein R^ is an unsubstituted phenyl group.

4. A method according to any one of claims 1 to 3 wherein X is fluorine.

5. A method of combating a resistant strain of whitefly at a locus infested by the resistant strain of whitefly comprising applying to the locus an amount effective to combat the whitefly of at least one compound of formula II

in which Ar, X and R¹ are as defined in any one of claims 1 to 4 and W is hydrogen as fluorine.

6. A method of combating a resistant strain of whitefly at a locus infested by the resistant strain of whitefly comprising applying to the locus an amount effective to combat the whitefly of at least one compound of formula III

wherein Ar, X and R* are as defined in any one of claims 1 to 4 and W is hydrogen or fluorine and either R² is hydrogen and R³ represents a cyclopropyl group or R^ and R² each represent a methyl group.

7. A method of combating a resistant strain of whitefly at a locus infested by the resistant strain of whitefly comprising applying to the locus an amount effective to combat the whitefly of at least one compound of formula IV

wherein Ar, X and R^ are as defined in any of claims 1 to 4 and either R² is hydrogen and R³ is CF₃ or R² and R³ are methyl.

8. A method of combating a resistant strain of whitefly comprising applying to the locus an amount effective to combat the whitefly of at least one compound of formula V

wherein Ar, X and R' are as defined in any one of claims 1 to 4 and W is hydrogen or fluorine.

9. A compound of formula V as defined in claim 8.

10. A method of combating a resistant strain of whitefly at a locus infested by the resistant strain of whitefly comprising applying to the locus an amount effective to combat the whitefly of at least one compound of formula VI

where Ar, X and R* are as defined in any one of claims 1 to 4, R² and R³ are methyl or R² is hydrogen and R³ is cyclopropyl or R² and R^J together form a cyclopropyl ring, and W is hydrogen or fluorine.

1 1. A method according to any one of the preceding claims wherein the compound of formulae I to VI is employed together with an inert carrier or diluent.

12. A method according to any one of the preceding claims wherein the infestation is by a resistant strain of Bemisia tabaci.