CA2235841A1 - Compounds for control of whitefly - Google Patents

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 CF3, isopropyl or cyclopropyl, or R2 and R3 are methyl, or R2 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, C1-C6 alkyl or haloalkyl groups.

Description

CA 0223~X41 1998-04-23 COMPO~NDS FQR CONTRQT, OF V~ LY
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 whiLeny(Bemi~i~ 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 ~ub~LldLe for fungi), creates harvesting difficulties (especially in cotton) and Lld~llliL'i a large number of plant viruses. It has become established in glasshouse horticulture in co.,~ ."~l Europe and poses a threat to agriculture in the UK despite efforts at ~lu~ulLille. The problem is exacerbated by the 10 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 wllileny strains.
Accordingly the present invention provides a method of cnmb~ting a resistant strain of whitefly at a locus infested by the .esi~L~lL strain of whik;ny compri~ing applying to the locus an amount effective to combat the whiLeny of at least one compound of formula I.

R 2~ / R 3 _~X (I) in which forrnula 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 CF3, isopropyl or cyclopropyl, or R2 and R3 are methyl,25 or R2 and R3 together form a cyclopropyl ring; and SUBSTlTUrE SHEEr (RULE ~6 Ar is a phenyl or naphthyl group optionally substituted by one or more halogen, alkoxy, haloalkoxy, methylenedioxy, Cl -C6 alkyl or haloalkyl groups.
Preferably Ar in forrnula I ,e~.~s~llL~ a phenyl group, preferably sllbstit~lte~l at the para position. Preferred substituents are halogen, particularly chlorine and fluorine and S aL~coxy, especially ethoxy.
R1 is preferably an ull,ub,liluLed phenyl group.
Those compounds where X is fluorine are especially preferred.
It will be appreciated tnat, dependent on the sll~stit l.ont~, optically active carbon atoms may be present. It is int~n~efl to include optically active as well as racemic forms 10 of such compounds. When Y and Z form a double bond, the compounds preferably have the two carbon-co. .I ;~i . . i . .g substituents in a ~ans configuration.
A particularly ~ler~ ,d group of compounds according to the invention are those of formula II
W ~f Ar~ ~ORI (II) 15 in which Ar, X and R1 are as defined above and W is hydrogen or fluorine. Compounds of forrnula 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. 9219612Ø
A further ~lG~ll~,d group of colll~oullds are those of formula III

R2~R3 ~OR1 (III) wherein Ar, X and R1 are as defined above, W is hydrogen or fluorine and either R2 is hydrogen and R3 l~pleselll~, a cyclopropyl group or R1 and R2 each l~ sent a methyl group. Compounds of formula III where W is hydrogen are disclosed in US Patent No. 4975451 and J~p~nl~se 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

R2 R3 I~X

Ar>~O ~OR1 (IV) wherein Ar, X and Rl are as defined above, R2 is hydrogen and R3 is CF3 or R2 and R3 are methyl. Such compounds and their ~lc~aldLion are disclosed in Baydar et al., Pestic. Sci. 1988, ~, 247-257, or UK Patent No. 2118167.
Also included within the present invention are compounds of forrnula V

A ~ ~ OR1 where Ar, X and Rl are dS defined above and W is hydrogen or, more preferably, fluorine.
Compounds of formula V where W is fluorine are novel and may be p~c~u~ed by the alaLion route generally described in co-pending UK Application No. 9308626.2 and15 exemplified herein.
Also included within the present invention is the use of compounds of formula VI
R2 R3 W I~X

A~--~ORl (VI) where Ar, X and Rl are as defined above. R2 and R3 are methyl or R2 is hydrogen and R3 is cyclopropyl or R2 and R3 together forrn a cyclopropyl ring, and W is hydrogen CA 0223~841 1998-04-23 or fluorine. Certain of such compounds and their pl~pdldlion are described in UK Patent No. 2120664.
Although the compounds of form~ ? I to VI as defined above have been generally proposed for use as insecticidal agents and, for example, UK Patent No. 2167749 m~ntion~
5 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 docllm~nt~ It was therefore ~ulyfl~ g to find that compounds of formula I had generally good activity against whiL~ny and even more surprising to find that that good activity was largely m~ ;..r~l against rc, ,i~L~IL whitefly strains. This m~ le~ e 10 of activity is in clear contrast to the majority of the comm~rcially 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 form~ tP~i in many 15 ways for use in comhating resistant whitefly. They can therefore be employed in a p~ 1 composition comrri~in~ 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 fliln--nt~ so as to provide compositions which can be form~ te~l for example as granules, dusts or em~ ifi~hle concentrates. Exarnples of diluents suitable for the ~ d~ion of granular compositions are porous materials such as pumice, gypsum or corn cob grits. Suitable diluents for the p.cp~hdLion of dusts include kaolin, bentonite, kieselguhr or talc. For the ~ ~d~ion of em~ ifi~ble concc--LIdles, 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.

CA 0223~841 1998-04-23 Dependent on the mode of use, the compositions may conveniently be applied to the locus of whitefly il~LdLion 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 5 of formula I and/or other ingredients, including another pesticidal material, eg. an insecticide, acaricide or fungicide, or a synergist.
It is int~n~led that the co,.lposilions 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 comhating resistant strains of Bemisia ~i, 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) Pl~dLion of compounds of Formula I.
Compounds of Formula I were ple~ ;d by the methods referenced in Table 1 below or in accordance with ~l~dLi~e Examples 1 to 5 below in which Examples 1 to 3 relate to the p.~,~dLion of intermediates and Examples 4 and 5 to compounds in accordance with the invention.

CA 0223~841 1998-04-23 Table1 R2 R3 ~ X

Z~ ~ OPh CompoundNo X Z-Y R2 R3 R4 Pl~d~ion 1 H CH=CH -CH2-CH2- Cl A

2 F CH=CH -CH2-CH2- Cl A
5 3 H CH=CF -CH2-CH2- Cl B
4 F CH=CF -CH2-CH2- Cl B
S H CH=CH -CH2-CH2- EtO A
6 F CH=CH -CH2-CH2- EtO A
7 H CH=CF -CH2-CH2- EtO B
10 8 F CH=CF -CH2-CH2- EtO B
9 H CH=CF -CH2-CH2- F B
F CH=CF -CH2-CH2- F B
11 H CH=CF CH3 CH3 Cl E
12 F CH=CF CH3 CH3 Cl E
15 13 H CH=CF CH3 CH3 EtO E
14 F CH=CF CH3 CH3 EtO E
H CH=CF H iPr Cl G
16 F CH=CF H iPr Cl G
17 H CH=CH H -~ Cl F
20 18 H CH=CF H -~ Cl E
19 F CH=CF H -~ Cl E
H CH=CF H -~ EtO E

Table 1 (continued) Compound No X Z-Y R2 R3 R4 Pl~a dlion 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
F CH2-~ H CF3 EtO D
26 H CH2-O H CF3 EtO D
27 F CH2-cH2 CH3 CH3 EtO

P~ lions were carried out in accordance with A UK Patent No. 2167749 B UK Application No. 9219612.0 C Baydar et al. Pestic. Sci. 1988, ~, 247-257 D UK Patent No. 2178739 E UKApplicationNo. 9308626.2 F US Patent No. 4975451 G As shown below H UK Patent No. 2118167 UK Patent No. 2120664 In the following Exarnplest 1 3C NMR peaks are listed as ~ igne-l peaks in the order indicated by the following diagram:
~I~r ; ~ !o~21 cl Equivocal ::15~ are indicated by ~ 5. - ;~ , a, b. Peaks not ~letected above the noise level are indicated by N. Coupling cor~lL, to fluorine are given in brackets, and are S in Hz.

Fx~rnrle 1 Methyl 4-(4-chloropherlyl!-2-fluoro-5-methylhex-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 10 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 dichlorofluoro~cet~te (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 ~Jlc, 7ulc. The residual oil was 15 chromatographed on silica gel using diethyl ether/hexane ( 1:9) to yield methyl 4-(4-chlol~he.lyl)-2-fluoro-5-methylhex-2-enoate 1.08g 34%.

Fx~mple 2 4-(4-Chloropher~l)- 1 -t2-fluoro-5-methylthex-2-enol Methyl 4-(4-chlorophenyl)-2-fluoro-5-methylhex-2-enoate prepared as described 20 in Example 1 (1.08 g) in dry diethyl ether (20 ml) was added dropwise to a stirred suspension of lithium aluminium hydride (0.3 g) in dry diethyl ether at 0 C. Stirring was c- ntinn~cl during 40 min, while the mixture warmed to room telll~c~dl lre. - 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 CA 0223~84l l998-04-23 W O 97/16067 PCT/~5G/'~2622 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%.

Fxarr~ple 3 4-(4-chlorophenvl!-2-fluoro-5-methvlhex-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) and pyridine (0.17 ml) at 0 C, and stirrmg was continued for 24 h while the mixture warmed to room tt~ eldLIlre. After addition of water ( 10 ml), the llli~lwe was ~tr~c t~-l with diethyl ether (3 x 20 ml) and the combined organic layers were washed with water 10 (3 x 10 ml) and evaporated under reduced ~lcs~ulc. 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%).

Fx~mr~le 4 4-(4-Chlorophenyl)-2-fluoro-5-methvl- 1 -(3-~henoxyphenyl)hex-2-ene A Grignard reagent, ~,c~cd from 3-phenoxyphenyl bromide (0.47 g) in dry tetrahydrofuran (3 ml) and m~ (34 mg) under nitrogen using iodine as an initiator at ca 40 C for 50 min, was cooled to room tcl~ dLulc then treated with cuprous bromide (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 LclllpcldLLu., overnight.
The ~ Lu~c 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 plC~ulc. The residue was purified by ~.cp~Live thin layer cl.. ~ Lography (solvent: diethyl ether/hexane; 1:9) and then ~lc~a,dlive high performance liquid 25 chromatography (column: Cl 8; solvent: methanol; flow rate: 3 ml/min) to afford 4-(4-chlorophenyl)-2-fluoro-5-methyl-1-(3-phenoxyphenyl)hex-2-ene (36 mg, 18%).
3C NMR spectrum:
142.7, 128.5a, 129.1a, 131.6, 47.3(3), 33.5, 20.9,20.2. 109.5(15), 158.0(256), 38.5(29), 138.4,117.3, 157.5b, 119.1, 129.8,123.6, 157.0b, 118.9, 129.8,123.3 g CA 0223~841 1998-04-23 W O 97/16067 . PCT/GB96/02622 Fxam~le S
4-(4-Chlorophenyl)-2-fluoro- 1 -(4-fluoro-3-phenoxvphenyl)5-methvlhex-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 m~gnpcium (28 mg) 5 and 4-(4-chlorophenyl)-2-fluoro-5-methylhex-2-enol (Example 3) (0.96 g). The residue after evaporation was purified by p~ Jaldli~re thin layer cllloll,dl{~graphy (solvent: diethyl ether/hexane; 1:9) to afford 4-(4-chlorophenyl)-2-fluoro-1-(4-fluoro-3-phenoxyphenyl)-5-methylhex-2-ene (27mg; 19.4%) 13C NMR spectrurn:
10 142.7, 128.5a, 129.0a, 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, 117.0(18), 124.8(7), 157.1, 117.3, 129.9, 123.3 B) Biological Data The compounds 1 to 26 idPntifi~cl in Table 1 were tested against susceptible andull strains of whitefly (Bemici~ tabaci~. The susceptible strain "SUD-S" was collected 15 from the Sudan in 1978 by Ciba-Geigy and subsequently labold~ / cultured to provide the standard laboratory ~llsc~lible strain. The resistant strain "BELZ" was collected from broccoli in Belize in November 1991. It is an example of this "poinsettia" strain of E~mi~i~ tabaci which is the biotype causing control difficulties in American field crops and glasshouses and in European glasshouses at the time of m~king the present patent20 application.
The tests were carried out as follows:
Acetone solutions (100 rnl) ofthe test compounds were placed in glass vials and evaporated with rotation to deposit a film of the compound. I~irty adult whiteflies were placed inside the vial, then after 60 mim-tçs, the treated insects were transferred onto 25 untreated cotton leaf discs which were kept moist on a bed of agar gel. The temperature was m~int~inlod at 25~C and mortalitv ~c~e~ed after 48 hours. Three replicates were used at each of S to 7 dose levels per compound. LCso values were calculated by using a computer software package ("Polo-PC" available from LeOra Software, Berkeley, California).

CA 0223~841 1998-04-23 W O 97/16067 PCT/~5G/02622 The LCso values are given in ppm (i.e. concentration of the acetone solution used) in Table 2 below. Several commercially available ~ylGLhluid esters and one organochlorineinsecticide (DDT) are included in the Table for reference.
- Table 2 Compound SUD-S LC50 BELZLC50 1 .1 2 0.8 6.7 3 2.2 7.7 4 0.67 30 S 0.94 6 0.42 1.1 7 0.35 4.2 8 1.1 2.6 9 1.3 17 lS 10 0.64 3.6 12 0.65 0.95 13 2.6 44 14 0.7 10 17 1.6 14 18 0.78 90 19 1.1 5.7 8.3 21 39.4 22 0.86 3.5 23 0.28 0.3 24 1.6 0.24 0.49 SUBSmUTE SHEEr (RULE 26~

Table 2 (ct ntinllPcl) Co.l.~oulld SW-S LC50 BELZ LCsO
26 0.82 1.05 27 0.67 l.S
Cyp~rmPthrin 9.1 170 Bir~.. Ll.. il~ 0.66 1.2 Fe.l~ dL~in 4.3 48 Tenul~lli-l 1.9 40 Fel~lullllill 2.0 22 Fenvalerate 3.9 83 Flucythrinate 5.9 480 Delt~mPthrin o 4 > 1000 PermPthrin 9.S 600 DDT 5.9 11 0 SUBSTITUTE SHEET (RULE 2~

Claims (12)

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;
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 CF3, isopropyl or cyclopropyl, or R2 and R3 are methyl,or R7 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, C1-C6 alkyl or haloalkyl groups, with the proviso that, when X is hydrogen, Y is O, Z is CH2, R2 and R3 are methyl, and Ar is an optionally substituted phenyl group, then the compound of formula I is employed without further insecticidal agents present.

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

3. A method according to claim 1 or 2 wherein R1 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 R1 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 R1 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 R1 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 R1 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, wherein W is fluorine.

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 R1 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 R3 together form a cyclopropyl ring, and W
is hydrogen or fluorine.

11. 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.