Field of the invention

This invention relates to new substituted pyrazoline derivatives with an enamide structure, processes for their preparation, as well as their use as pesticides, especially as insecticides and acaricides.

Prior Art

Pyrazolines with insecticidal activity are already well known. There are a number of patents describing such compounds. In particular a number of patent applications, e.g. EP 227 055 and DE 4 005 114, disclose pyrazolines which have a carbamoyl structure at the 1-position.

The disadvantage of many of the prior art compounds is the insufficient activity and/or spectrum and/or have an unacceptable toxicity to mammals or beneficial insects and/or mites. We have now found that the novel group of compounds of the present invention overcome these disadvantages.

Description of the Invention

According to the invention there is provided a pyrazoline derivative of general formula I

( I )

in which

R ¹ , R ² and R ⁴ , which may be the same or different, are hydrogen, or are phenyl, cycloalkyl, cycloalkenyl, alkyl, alkoxycarbonyl, alkylcarbonyl or alkenyl, each of which is optionally substituted, or R ¹ and R ² together form an optionally benzo fused alkylene group, R ³ and R ⁵ , which may be the same or different, are hydrogen or optionally substituted alkyl, R ⁶ , R ⁷ and R ⁸ , which may be the same or different are hydrogen, nitro or cyano or are phenyl, cycloalkyl, cycloalkenyl, alkyl, alkoxy, alkylthio, alkoxycarbonyl, alkylcarbonyl or alkenyl, each of which is optionally substituted, or R ⁶ and R ⁷ together with the C-C double bond attached to the nitrogen form an optionally substituted cycloalkenyl ring.

The invention includes isomeric forms and as well as mixtures of isomers.

Particularly preferred compounds of formula I are those where

R ¹ , R ² and R ⁴ , which may be the same or different, are hydrogen, or are phenyl, optionally substituted by one or more of the same or different, halogen, nitro, cyano, C _β -alkyl, C _j . ₆ -alkoxy, C^g-alkoxycarbonyl, C^-alkylthio, halo-C^-alkyl, halo-C _j . _g -alkoxy, halo-C _j . ₆ -alkoxycarbonyl, halo- C _j ^-alkylthio, C^g-alkylsulfonyl or halo-C _j . _g -alkylsulfonyl, or are C _5.8 -cycloalkyl or C ₅ . ₈ -cycloalkenyl, each of which is optionally substituted by one or more of the same or different, cyano, C^g-alkyl, halo-C^g-alkyl, C^g-alkoxy,

halo-C _j .g-alkoxy, C ₁ . ₆ -alkylthio, halo-C _j.6 -alkylthio, C _j ^-alkoxycarbonyl or halσ-C^-alkoxycarbonyl, or are C _j ^-alkyl, C _l . ₆ -alkoxycarbonyl, C^-alkylcarbonyl or C^-alkenyl, each of which is optionally substituted by halogen, nitro or cyano,

R ³ and R ⁵ , which may be the same or different, are hydrogen or C _j ^-alkyl, optionally substituted by halogen, nitro or cyano, R ⁶ , R ⁷ and R ⁸ , which may be the same or different are hydrogen, nitro or cyano or are phenyl, optionally substituted by one or more of the same or different, halogen, nitro, cyano, C^-alkyl, C _j .g-alkoxy, C _j ^-alkoxycarbonyl, C^g-alkylthio, halo-C^ _g -alkyl, halo-C g-alkoxy, halo-C _j . ₆ -alkoxycarbonyl, halo- C _j ^-alkylthio, C^-alkylsulfonyl or halo-

C^-alkylsulfonyl, or are C ₅ . ₈ -cycloalkyl or C ₅ . ₈ -cycloalkenyl, each of which is optionally substituted by one or more of the same or different, cyano, C^g-alkyl, halo-C^-alkyl, C _j .g-alkoxy, halo- C _j . _g -alkoxy, C^-alkylthio, halo-C^-alkylthio,

C _] ,. ₆ -alkoxycarbonyl or halo-C _j ^-alkoxycarbonyl , or are C _μ6 -alkyl , C^-alkoxycarbonyl , C^-alkylcarbonyl or C g-alkenyl , each of which is optionally substituted by halogen , nitro or cyano , or R ⁶ and R ⁷ together with the C-C double bond attached to the nitrogen form a C _5. g-cycloalkenyl ring , optionally substituted by one or more of the same or different , halogen , cyano , C _j .g-alkyl , C^-alkoxy , C^g-alkylthio , C ₁ . ₆ -alkoxycarbonyl , halo-C^-alkyl , halo-C^-alkoxy , halo-C _g -alkylthio or halo-C,_ . ₆ -alkoxycarbonyl ,

C^-alkylsulf onyl .

Preferably at least one of R ¹ , R ² and R ⁴ , is optionally substituted phenyl and it is particularly preferred that

both R ¹ and R ² are optionally substituted phenyl. R ⁴ is preferably hydrogen.

Particularly preferred substituents on these R ¹ and R ² phenyls are halogen, cyano or halo-C^-alkoxy.

For the moiety in the 1-position of the pyrazoline, it is generally preferred that R ⁸ is hydrogen and either R ⁶ is hydrogen, in which case R' is optionally substituted phenyl, in which the substituents are preferably halogen, nitro, cyano, C^-alkyl, C^-alkoxy, halo-C^-alkyl or halo-C _j . ₆ -alkoxy, or R ⁶ and R ⁷ together with the C-C double bond attached to the nitrogen form an optionally substituted C ₅ _ ₈ -cycloalkenyl ring, preferably a cyclohexenyl ring, in which the substituents are preferably halogen, cyano, C^g-alkyl, C^-alkoxy, halo- C g-alkyl or halo-C^-alkoxy, and especially C^-alkyl, or halo-C _j ^-alkyl.

It is preferred that R ³ , R ⁴ and R ⁵ , are all hydrogen,

By the term "halogen" it is preferably understood to mean fluorine, chlorine or bromine.

Particularly preferred are compounds of formula I in which R ¹ is 4-cyanophenyl, 4-fluorophenyl, 4-chlorophenyl,

4-isopropoxyphenyl, 4-butoxyphenyl or

4-(2,2,2-trifluoroethoxy)phenyl, R ² is 4-cyanophenyl, 4-fluorophenyl- or 4-chlorophenyl or 4-isopropoxyphenyl, R ³ , R ⁴ , R ⁵ and R ⁸ are hydrogen, and either a) R ⁶ is hydrogen and R ⁷ is 4-trifluoromethylphenyl,

3-trifluoro ethylphenyl, 4-nitrophenyl-

4-trifluoromethoxyphenyl, 3-trifluoromethoxyphenyl,

b) R ⁶ and R' together with the C-C double bond on the nitrogen form cyclohex-l-enyl, 4-methylcyclohex- 1-enyl or 4-trifluoromethylcyclohex-i-enyl.

The pyrazoline derivatives of the invention of general formula I, can be prepared by reacting a pyrazoline derivative of general formula II

I

H

in which R ¹ , R ² , R , R ⁴ and R ⁵ have the meanings given above, with an isocyanate of general formula III

6

in which R ⁶ , R ⁷ and R ⁸ have the meanings given above, optionally in the presence of a base.

For example if one uses 3 ,4-bis-(4-chlorophenyl) - 2-pyrazoline and 4-trifluoromethylcyclohex-1-enyl isocyanate as starting materials, the reaction can be illustrated as follows.

The pyrazoline derivatives of general formula II are known or can be obtained in known manner, for example as described in J. Agric. Food Che . Vol. 25, No. 5, (1977) 987, J. Agric. Food Che . Vol. 27, No. 2, (1979) , 406, J. Agric. Food Chem. Vol. 26, No. 4, (1973) , 915; USP 4,439,440; EP-A 113 213; EP-A 053 424, USP 4,663,341, DE-A 3 628 647 or EP-A 236 346.

The isocyanates of general formula III are known or can be obtained in known manner, for example as described in J. Org. Chem. 49, (1984), 4569-4571.

Those compounds of formula III where R ⁶ and R' "together with the C-C double bond on the nitrogen form a cyclohexenyl ring, substi uted by halo-C _[ . ₆ -alkyl, halo-C _j ^- alkoxy, halo-C^-alkylthio, C _j . ₆ -alkoxycarbonyl or halo- C _j. g-alkoxycarbonyl, are new and form part of the invention. In these cases some of the precursors may also be novel and also form part of the invention.

Particular novel compounds that can be mentioned are : 4-trif luoromethylcyclohex-i-enyl isocyanate ,

the mixed anhydride from

4-trifluoromethylcyclohex-l-enecarboxylic acid and ethyl hydrogen carbonate,

4-trifluoromethylcyclohex-l-enecarbonyl chloride, 4-trifluoromethylcyclohex-i-enecarbonyl azide, 4-trifluoromethylcyclohex-i-enecarboxylic acid, 4-trifluoromethyleyclohex-i-enecarbonitrile, l-hydroxy-4-trifluoromethylcyclohexane- 1-carbonitrile and 4-trifluoromethyl-1-trimethyIsilyloxycyclohexane- 1-carbonitrile.

In some situations the isocyanate can be formed in situ and in these cases it may be possible to use the so formed isocyanate in the next reaction stage without isolation and/or purification.

The reaction between the compounds of formula II and formula III is preferably carried out in an organic solvent or mixture of solvents at a temperature of from -20 to 150°C, preferably at 20 to 90°C.

Suitable solvent are liquids which are inert to the reactants, e.g aliphatic, alicyclic or aromatic hydrocarbons, which are optionally chlorinated, e.g. pentane, hexane, cyclohexane, petroleum ether, benzene, toluene, xylene, dichloromethane, chloroform, carbon tetrachloride, ethylene dichloride, trichloroethylene or chlorobenzene; ethers, such as diethyl ether, methyl ethyl ether, diisopropyl ether, dibutyl ether, methyl tert-butyl ether, dioxane or tetrahydrofuran; nitriles, such as acetonitrile, propionitrile or benzonitrile; esters, such as ethyl acetate or a yl acetate; amides, such as dimethylformamide; N-methylpyrrolidone or hexamethylphosphoric triamide, as well as sulfones, such as dimethyl sulfoxide or sulfolane.

As bases there can mentioned aliphatic, aromatic an _d heterocyclic amines, e.g. triethyla ine, dimethylaniline or pyridine.

The reaction can be carried out at atmospheric pressure although higher or lower pressures may be used.

The compounds of the invention prepared by these processes can be isolated from the reaction mixtures in conventional manner, for example by distillation of the solvent at normal or reduced pressure, by precipitation with water or by extraction. A higher level of purity can be achieved as a rule by column chro atography or recrystallisation.

Besides the process described, compounds of formula I nay also be obtained by reacting a pyrazoline derivative of general formula IV

in which R ¹ , R ² , R ³ , R ⁴ and R ⁵ have the meanings given above, with a carbonyl compound of general formula V

(V)

or an enol ether of general formula VI

in which R ⁶ , R' and R ^s have the meanings given above, and ⁹ is C _[ _ ₆ -alkyl, optionally in the presence of an acid.

The compounds of the invention have insecticical and acaricidal activity and are suitable for combating parasites of humans and domestic animals as well as plant pests. Examples are Lepidoptera, such as Plutella xylostella , Spodoptera littoralis, Heiiothls armigera, Heliothis vireεcens and Pier is brasεicae ; Diptera, ^" such as Gasterophilus, Cochliomyia, Muεca domeεtica , Ceratitis capitata , ∑rioischia braεεicae , Lucilia εericata and β.eάeε aegypti ; Hemiptera, including aphids such as Megoura viciae and leafhoppers, such as Nilaparvata lugens and Nephotettix cincticepε; Coleoptera, such as Phaedon cochleariae, Anthonoiπuε grandis and corn rootworms Diabrotica spp., e.g. Diabrotica undeci punctata) ; Orthoptera, such as Blatiella germanica ; ticks, such as Boop ilus microplus and lice, such as Damalinia bovis and Linognathus vituli as well as mites such as Tetranychuε urticae and Panonychus ulmi .

The compounds of the invention can be used either alone or in mixture with each other or another insecticide. Optionally other plant protection or pesticidal compositions, such as for example insecticides, acaricides or fungicides can be added depending on the desired result.

An improvement in the intensity and speed of action can be obtained, for example, by addition of suitable adjuvants, such as organic solvents, wetting agents and oils. Such additives may allow a decrease in the dose.

Suitable mixture partners may also include phospholipids, e.g. such as from the group phosphatidylcholine, hydratεd phosphatidylcholine, phosphatidylethanolamine, N-acyl-phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, lysolecithin or phosphatidylglycerol.

The designated active ingredients or their mixtures can suitably be used, for example, as powders, dusts, granules, solutions, emulsions or suspensions, with the addition of liquid and/or solid carriers and/or diluents and, optionally, binding, wetting, emulsifying and/or dispersing adjuvants.

Suitable liquid carriers are, for example aliphatic and aromatic hydrocarbons such as benzene, toluene, xylene, cyclohexanone, isophorone, dimethyl sulfoxide, dimethylformamide, other mineral-oil fractions and plant oils.

Suitable solid carriers include mineral earths, e.g. tonsil, silica gel, talcum, kaolin, attapulgite, limestone, silicic acid and plant products, e.g. flours.

As surface-active agents there can be used for example calcium lignosulfonate, polyoxyethylenealkylphenyl ether, naphthalenesulfonic acids and their salts, phenolsulfonic acids and their salts, formaldehyde condensates, fatty alcohol sulfates, as well as substituted benzenesulfonic acids and their salts.

The percentage of the active ingredient ( s ) in the various

preparations can vary within wide limits. For example, the compositions can contain about 10 to 90 percent by weight active ingredients, and about 90 to 10 percent by weight liquid or solid carriers, as well as, optionally up to 20 percent by weight of surfactant.

The agents can be applied in customary fashion, for example with water as the carrier in spray mixture volumes of approximately 100 to 1,000 1/ha. The agents can be applied using low-volume or ultra-low-volume techniques or in the form of so-called microgranules.

The preparation of these formulations can be carried out in known manner, for example by milling or mixing processes. Optionally, individual components can be mixed just before use for example by the commonly used so-called tank-mixing method.

Formulations can be prepared, for example, from the following ingredients.

Al WETTABLE POWDER 30 percent by weight active ingredient 15 percent by weight kaolin 5 percent by weight of surfactant based on of the sodium salt of N-methyl-N-oleyltaurine and calcium lignosulfonate

A2 WETTABLE POWDER

20 percent by weight active ingredient

35 percent by weight fuller's earth

8 percent by weight calcium lignosulfonate 2 percent by weight sodium salt of

N-methyl-N-oleyltaurine 35 percent by weight silicic acid

B PASTE 45 percent by weight active ingredient

5 percent by weight sodium aluminium silicate 15 percent by weight cetylpolyglycol ether with 8 moles ethylene oxide 2 percent by weight spindle oil 10 percent by weight polyethylene glycol 23 parts water

C EMULSIFIABLE CONCENTRATE

20 percent by weight active ingredient 75 percent by weight isophorone

5 percent by weight of a mixture of ionic and nonionic surfactants

The following examples illustrate the preparation of compounds according to the invention.

Preparation Example 1 , 4-bis-(4-chloroohenyl) -N- (4-trifluoro ethyl-

1-cvclohexen-l-yl -4 , 5-dihvdro ^p yrazole-l-carboxamide

1.70 g (7.76 mmol) 4-trifluoromethylcyclohex-1-enecarbonyl azide was dissolved in 20 ml absolute toluene and under inert conditions (nitrogen), heated to 100°C, until no more gas evolution was observed, In this way, 4-trifluoromethyl-cyclohex-l-enyl isocyanate was formed. The mixture was then cooled to 0°C, and 2.26 g (7.76 mmol) 3 , 4-bis-(4-chloro-phenyl) -4 , 5-dihydropyrazole added. After stirring for 10 minutes at 0°C, the mixture was allowed to rise to room temperature and stirred for a further hour. It was diluted with ca. 20 ml hexane and the product crystallised out. It was suction filtered and washed with hexane.

Yield: 2.15 g (52% of theory) colourless crystals m.p.: 167-169°C R _f = 0.84 (silica gel/ethyl acetate)

Preparation of the starting materials

4-Trifluoromethvlcvclohex-1-enecarbonitrile

12.72 g (76.56 mmol) 4-Trifluoromethylcyclohexanone was added to 50 ml absolute toluene. 0.6 g zinc iodide was added followed by dropwise addition of 11.08 g (111.01 mmol) trimethylsilyl cyanide. At the end of the exothermic reaction, the mixture was stirred for a further 2 hours.

125 ml Pyridine and 35.22 g (229.68 mmol) phosphorus oxychloride was added and the mixture heated for ca. 8 hours at ca. 100°C. The mixture was cooled to room temperature and added to ice/hydrochloric acid mixture and extracted with ether. The combined organic phases were washed with 2M hydrochloric acid, saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride, dried over magnesium sulfate and concentrated in a rotary evaporator. The residue was fractionally distilled in vacuo.

Yield: 8 g (60% of theory) colourless crystals m.p. : 35-40°C b.p. : 50°C/0.3 mm

4-Trifluoromethylcvclohex-l-enecarboxylic acid

8.0 g (45.68 mmol) 4-Trifluoromethylcyclohex- l-enecarbonitrile was heated with 50 ml phosphoric acid (85%) for 8 hours on an oil bath at 140°C, with vigorous stirring. The mixture was cooled, 100 ml water added and extracted with ethyl acetate. The organic phase was extracted twice with 100 ml 2M sodium hydroxide. The aqueous ^' phase was washed several times with ethyl acetate. It was then acidified with 5M hydrochloric acid and again extracted with ethyl acetate. The organic phase was dried over magnesium sulfate and concentrated in a rotary evaporator. The residue was treated with cold hexane and concentrated in vacuo .

Yield: 6.0 g (68% of theory) colourless crystals m.p.: 192-194°C R _t - = 0.57 (silica gel/ethyl acetate)

4-Trifluoromethylcvclohex-l-enecarbonyl a ide

4.0 g (20.6 mmol) 4-Trifluoromethylcyclohex-1-ene- carboxylic acid and 2.53 g (25.54 mmol) triethylamine was dissolved in 40 ml absolute acetone. At 0°C, a solution of 2.24 g (20.60 mmol) ethyl chloroformate in 20 ml absolute acetone was added dropwise over ca. 30 ins. The mixture was stirred for ca. 1 h and the precipitated hvdrochloride suction filtered. The acetone was removed using a rotary evaporator. The residue treated at a temperature below

15°C with a solution of 1.69 g (26.03 mmol) sodium azide in 20 ml water/acetone (1:1) . The mixture was stirred vigorously for ca. 1 hour, extracted with ether, and the extract dried over potassium carbonate and a molecular sieve and concentrated in vacuo at room temperature. The crude product was then used without further purification.

In a similar manner, the following compounds of formula in which R ³ , R ^J and R ⁸ are hydrogen were prepared:

Rl R^ R < Mp ( ° c '

_σ c H c ^: w / -α K ^■ 78

CF,

.0 C H C .= - H -CH2CH2-CH2CK2- 106-6S

W // H -CH2CH2-CK2CH2- 174-76

_O C H w /r o^ H HJCHJ-CH— CH _j - 172-74

.c; — C;-I ₂ CΠ ₂ -CH a - ₁₅₄ . ₅₇

W ^ '/ H α-

No R^ R R° M ( ³ C)

.CH.-CH-CH,- 174-175

^' 14 -r> -CH

-Q- ^™ CF,

o R ^J - R2 R4 R ^c M _{? C)}

I

II

91 Foaai

UP. ^J R^ MP (° ^C )

25 -4 -* " ^{~α E E} 156-158

No R ^d - P (°C)

CF

J» w // / ' 129-130

CF ₃ — ( ) Isomer I

II

I

II

No Rl R2 ^Λ - R7 Mp ( ³ C)

SUBSTITUTE SHEET (RULE 2b)

No l R- R< R' Mp ( ³ <

2 - - ^σ ' \\ / H Fear.

X T C F,

Rl 2 R- R7 Mo ( ^s c)

The following examples illustrate the possibilities for use of the compounds of the invention.

Test Example A Activity aσainst adult cotton boll-weevil ( Antkonomus σrandiε)

The compounds of the invention were made up as aqueous preparations at a concentration of 0.1%. 0.2 ml of this preparation was pipetted onto feed material, in a polystyrene petri dish and 0.2 ml onto the bottom of the petri dish. After drying, 5 adult (2 day old) cotton boll- weevils (Anthonomuε grandiε) were counted into the dishes. The closed dishes were left for up to 7 days at 25°C under extended daylight conditions. The % mortality of the weevils at the end of the test indicated the level of activity.

The compounds of Examples 1-10 showed 80 - 100% activity.

Test Example B

Activity against larvae fLl of the cotton bollwor

(Heliothis vireεcenε)

The compounds of the invention were tested in a similar manner to Test Example A using 10 LI of the cotton bollworm (Heliothis virescens ) on the feed material.

The compounds of Examples l-io showed 80 - 100% activity .