CA1140556A - Pyrazole derivatives and their use as pesticides - Google Patents

Abstract

ABSTRACT

There are provided pyrazole derivatives of general formula wherein R1 represents a phenyl, pyridyl or naphthyl group option-ally substituted by one or more substituents selected from halogen, cyano, amino, and mono- and di-(C1-4 alkyl)-amino; R2 represents a phenyl group, a fluorophenyl group or a C1-6 alkyl group option-ally substituted by a (C1-6 alkoxy)carbonyl group; and R3 repre-sents a methyl or ethyl group, excluding 3-pheny1-5-methylthio-1-phenyl-pyrazole; methods for their preparation; compositions containing them and their use as pesticides.
Compounds of formula I exbibit pesticidal, especially acarid ovicidal, activity.

Description

., Pyrazole derivatives and their use as pesticides The present invention relates to pyrazole derivatives, to their preparation, to their use as pesticides, particularly insecticides and acaricides, and to pesticidal compositions containing them.
U.K. Pa-ten-t Speci~ication No. 1,~88,285 discloses a broad class of pyrazole derivatives as herbicides. This class of pyrazole derivatives includes aIkyltbiopyrazoles, but there are no individual N-substituted 3-(or 5-)alkylthiopyrazoles specifi-cally described and there is no suggestion that any of the pyrazole derivati~es mi6ht have insecticidal or acaricidal activity.
Michaelis and Willert, Annalen der Chemie, 358, 171-182 (1908) describe 1,3-diphenyl-5-methylthiopyrazole. However, no indication of any utility is given ~or this compound. More particularly there is no suggestio~ that it might possess any pesticidal activity.
The Applicants have surprisingly discovered a class of pyrazole derivatives, more specifically N-substituted alkylthio-pyrazole derivatives, possessing pesticidal activity.
According to the invention, there~ore, there is provided a pyrazole derivative of general formula:-Rl ~\
R N 1 S~3 (I) wherein R represents a phenyl, pyridyl or naphthyl group op-tionally substituted by one or more substituents selected from halogen, cyano, amino, and mono- and di-(Cl 4 alkyl)--amino; R
represents a phenyl group, a ~luorophenyl group or a Cl 6 alkyl group optionally substituted by a (Cl 6 alkoxy)carbonyl group;
and R3 represents a methyl or ethyl group, excluding 3-phenyl-5-methylthio-l-phenyl-pyrazole.
It is preferred for R to be a phenyl group optionally substituted by one or two halogen atoms; or, when R is a Cl 6 10 alkyl group optionally substituted by a (Cl 6 alkoxy)carbonyl group, a dimethylaminophenyl group or a napthyl group; or, when R represents a phenyl or fluorophenyl group, a pyridyl group.
Advantageously, R represents a phenyl group optionally sub~
stituted at the 3- and/or 4-positions by fluorine, chlorine or 15 bromine, or at the 4-position by a dimethylamino group; a 4-~ pyridyl group or a 2-naphthyl group.
; An alkyl or alkoxy group in the compound of formula I may be of straight-chain or branched-chain configuration.
It is pre~erred for R to represent a phenyl group, a 20 fluorophenyl group, a Cl 4 alkyl group or an ethoxycarbonylmethyl group.
Advantageously t'ne carbon atom to ~hich the group -SR3 is attached is at the 3-position in the pyrazolyl ring.
Particularly preferred derivatives of formula I are those 25 wherein ~ is a phenyl group substituted at the 4-position by a fluorine~ chlorine or brcmine atom, R is a phenyl group or a

2-methylpropyl group, R3 is a methyl or ethyl group and the carbon atom to which the group -SR3 is attached is at the 3-position in the pyrazolyl ring.
3o The derivatives of formula I may be prepared in accordance with the invention by a process which comprises reacting a compound of general formula Rl C - CH = C / ~II) 0 ~ \ SR3 " ~4~55~

3.
wherein R and R3 are as defined above, with a compound o~
~eneral formula R~NH-NH2 (III) or an acid-addition salt thereof wherein R is R as defined above or hydrogen, followed when R is hydrogen by reacting -the resulting co~pound with a compo~d of general for~ula R5X, wherein R5 is an optionally substituted alkyl group and X is a halogen atom, to produce a compound of formula I wherein R is The above process generally results in the production of a mixture of the 3-alkylthio and 5-aIkylthio isomers of the pyra-zolyl derivatives of formula I with one or other isomer pre-dominating, depending on the specific reaction conditions em-ployed. These isomers may be separated from the reaction mixture and from each other in known manner, e.g. by chromatographic methods.
Where R represents an optionally substituted aryl group?
the process may be effected by mixing directly together the compounds of formula II and III and heating the mixture at a temperature in the range of ~rom 100C to 200C, preferably 130C
to 170C. The 5-alkylthio-isomer tends to predominate in the resulting product of formula I.
More generally however, and particularly in the case where the compound of formula III is hydrazine or an optionally substi-tuted alkylhydrazine, the compound of formula II and the compound of formula III or its acid-addition salt are reacted together in an inert solvent at e1evated temperature, conveniently the reflux temperature of the reaction mixture. Polar solvents are pre-ferred. Examples of suitable solvents for use in the process when the compound of formula III is an optionally substituted aryl hydrazine are acetic acid and pyridine. Examples of suit-able solvents for use in the process when the compound of formula III is hydrazine or an optionally substituted alkylhydrazine are acetic acid, pyridine and liquid Cl ~ alkanols, such as ethanol.

~' , :

3~5

4.
~ hen R i5 other than hydrogen in the compound of fcrmula III, it has been found that 5-aIkylthio isomers of formula I are generally the predominant prcducts when pyridine is used as solvent. However, when acetic acid is used as solvent and an acid-addition salt, e.g. the hydrochloride, of the compound of formula I is -mployed, the predominant product is the 3-alkylthio isomer of formula I.
When the compound of formula III is hydrazine, the product of the reaction with the compound of formula II is an inter-mediate of formula R1 ..

~ (IV) H ~ SR3 15wherein R and R3 are as defined above and the hydrogen atom is attached to one of the nitrogen atoms of the pyra~olyl ring.
It will be appreciated by those skilled in the art that a compound of formula I~ will be a tautomeric mixture of 5-alkyl-thio and 3-alkylthio isomers.
The reaction between the intermediate of formula IV and the compound of formula R5X, wherein R5 is an optionally substituted alkyl group and X is a halogen atom, is conveniently ef~ected in a single solvent phase, or in a two-phase solvent system con-taining a phase-transfer ea~alyst, in the presence of a base, at a temperature in the range from ambient temperature to the reflux temperature of the reaction mixture. It is preferred for X to be a bromine or iodine atom. Suitable bases include alkali metal and alkaline earth metal hydrides, alkoxides or carbonates, tertiary amines and basic ion-exchange resins. Preferred amine bases contain one or more Cl 4 alkyl andlor benzyl groups, or are heterocyclic amine bases having 5 or 6 ring atoms and containing the nitrogen atom and optionally an oxygen, a sulphur or an 35~6 additional nitrogen atom atta~hed to carbon atoms in the ring, for example ~-methylpyrrolidine, N-methy-lmorpholine or N-methyl-piperidine. Potassium and sodium hydride, ethoxide and hydroxide are preferred bases.
The choice of solvent is dependent to some extent on the nature of the chosen base. EIowever polar solvents are preferred, for example liquid Cl 4 alkanols such as ethanol, C2 6 ethers and cyclic ethers, such as tetrahydrofuran. A preferred two-phase solvent system comprises a mixture of water and a ua-ter-immi-scible polar solvent such as methylene chloride, together with a phase-transfer catalyst as described in U.K. Patent Speci~ication ; ~o. 1,540,6~2. Tetra-n-butyl ammonium bromide is a preferred phase-transfer catalyst.
~he compounds of formulae II and III are known or can be prepared from known compounds by known methcds. A suitable method of preparing compounds of formula II is described by Shahak and Sasson in Tetrahedron Letters, 1973, 4207.
Compounds of formula I have exhibited pesticidal, partic-ularly insecticidal and acaricidal, including acarid ovicidal, activity. The compounds of formula I are conveniently formulated as a pesticidal composition which comprises as active ingredient a compound of the general formula I, in association with an inert carrier. ~he invention also pro~ides a method of combating pests at a locus, which comprises applying to that locus a compound of the general formula I or a pesticidal composition according to the invention.
A carrier in a composition of the in~ention may be a solid or a liquid, including a material w~ich is normally gaseous but which has been compressed to form a liquid, inorganic or organic, 3o and of sythetic or natural origin. ~he active ingredient is suitably formulated with at least one carrier to facilitate its application to the locus, for example plants, seeds or soil, to be treated, or to facilitate storage, transport or handling.
Preferably a composition of the invention contains at least 3S5~

two carriers, at least one of which is a surface-active agent.
The surface-active agent may be an emulsifier, a dispersing agent or a wetting agent; it may be non-ionic or ionic. Pesticidal compositions are generally formulated and transported in a concentrated form which is sub~equently diluted by the farmer or other user before application. A surface-active agent faci-litates -this process of dilution.
Any of the carriers commonly used in the formulation of pesticides may be used in the compositions of the invention, and suitable examples of these are to be found, for example, in British Patent Specification No. 1,232,930.
The composition of the invention may for example be form-ulated as a wettable powder, microcapsules, a dust, granules, a solution, an emulsifiable concentrate, an emulsion, a suspension concentrate or an aerosol. The composition may have controlled release properties, or may be suitable for use as a bait.
Wettable powders usually contain 25, 50 or 75%w of active ingredient and may contain, in addition to inert solid material, 3-10% w of a dispersing agent and, where necessary, 0-10% w of a stabiliser, a penetrant and/or a sticker. A dust is usually formulated as a dust concentrate h&ving a composition similar to that of a wettable powder but without a dispersant, and is diluted in the field with further solid carrier to give a compo-sition usually containing ~-10% w of active ingredient.
Granules usually hsve a size in the range of from 10 to 100 BS mesh ~1.676-0.152 mm) and may be manufactured by ag~lomeration or impregnation techniques. Generally, granules will contain ~-25% w active ingredient and 0-10% w of additives, for example a stabiliser, slow release modifier and/or a binding agent.
~0 Emulsifiable concentrates usually contain, in addition to a solvent, and~ when necessary, co-solvent, 10-50% w/v active ingredient, 2-20% w/v emulsifier and 0-20% w/v of other add-itives, for example a stabiliser, a penetrant and/or a corrosion inhibitor. A suspension concentrate is a stable, non-sedimen-

5~6 ting, flowable product and usually contains 10-75% w active ingredient, 0.5-15% w of dispersing agent, 0.1-10% w of sus-pending agent, for example protective colloid and/or a thixo-tropic agent, and 0-10% w of other additives including, for example, a defoamer, a corrosion inhibitor, a stabiliser, a penetra~t and/or a stic~er, and as dispersant, water or an organic liquid in which the active ingredient is substatially insoluble; certain organic additives and/or inorganic salts may be dissolved in the dispersant to assist in preventing sedimen-tation or as anti-freeze for water.
The aqueous dispersions and emulsions formed by diluting a wettable powder or an emulsifiable concentrate cf the invention with water, also lie within the scope of the present in~ention.
Such dispersions and emulsions may be of the water-in-oil or of the oil-in-water ty~e, and may ha~e a thick "mayonnaisel'-like consistency.
A composition of the invention may also contain other ingredients, for example, one or more other compounds possessing pesticidal, herbicidal or fungicidal properties, or attractants, for example pheromones or food ingredients, for use in baits and trap formulations.
The in~ention will be better understood from the following Examples, of which Examples 3 to 30 relate to the preparation of compounds according to the invention, and Examples 1 and 2 relate to the preparation of intermediates.
Example 1 1-(4-chlorophenyl)-3,3-bis(ethylthio)-2-propen-1-one A solution of ~-chloroacetophenone (30.9 g, 0.2 mole) in dry tetrahydrofuran ("~HF") (100 ml) was added over 1 hour to a stirred suspension of sodium hydride (9.6 g, 0.4 mole) in the same solvent (250 ml). A solution of carbon disulphide (12.0 ml, 0.2 mole) in dry THF (200 ml) was then added over 1 hour and the resulting reaction mixture was stirred at 40 ~ for 2 hours.
Ethyl bromide (43.6 g, 0.4 mole) in THF (200 ml) was added over 30 mins. and the reaction temperature was maintained at about 40 C for a further 2 hours, and was finally heated under reflux for 1 hour. ~ter cooling, ice was added cautiously to destroy any excess sodium hydride and the solvent was removed under reduced pressure. The residue was shaken with chloroform and water and the organic phase was separated, ~ashed with more water and finally dried (MgS04). Evapora-tion of the dried extr&ct afforded a sticky solid which was recrystallised from methanol to give l-(4-chlorophenyl)-3,3-bis(ethylthio)-2-propen-1-one (Yield 25.0 g, 44%), m.p. 60-63C.
ArLalysi S
C H
Calculated for C13 15 2 5 5 5.2%
Found 54 5 5.2%
15 Example 2 3(5)-(4-chlorophenyl)-5(3)-methylthiopyrazole A solution of 1-(4-chlorophenyl~-3,3-bis(methylthio)-2-- propen-l-one (12.9 g, 0.05 mole) and hydrazine hydrate (3.0 g, o.o6 mole) in ethanol (25 ml) was heated under reflux for 5~
hours. The solvent was then removed under reduced pressure and the residue was suspended in water and extracted with chloroform.
The extract was dried (MgS04) and evaporated to yieLd a crude product which was purified by crystallisation from toluene/80-100 petroleum ether to give the pure title product as colourless crystals (yield 9.7 g, 86%) m.p. 1}1-113C.
Analysis:
; C H
Calculated for CloXgClN2S 53.4 4.0 12.5 Found 53.6 3.9 12.4%
30 Examples 3 and 4 5-(4-bromoph nyl)-3-methylthio-1-phenylpyrazole and 3-(4-bromophenyl)-5-methylthic-1-phenylpyrazole 1-(4-Bromophenyl)-3,3-bis(methylthio)-2-propen-1-one (3.0 g, 0.010 mole) and phenylhydrazine (1.2 g, 0.011 mole) were mixed 35~;

toge-ther and the resultirlg intimate mixture was heated a-t 130C
for 2 hours. After cooling, the reaction mixture, was dissolved in chloroform and the solution was washed with I~ hydrochloric acid follow~d by water. The resulting solution was dried (MgS04) and evaporated to give a mixture of the isomeric title pyrazoles which were separated and purified by chromatography on silica gel using chloroform as eluant. The first compound eluted was 3-(4-bromophenyl)-5-methylthio-1-phenylpyrazole (yield 1.5 g, 44%, m.p. 63-65 C) followed by 5-(4-bromophenyl)-3-methylthio-1-10 phenylp~razole (yield 1.3 g, 38%, m.p. 79-80 C).
Anal,ysis C H
Calculated for C16H13~r~2S 3.8 8.1%
Found: Example 3 56.1 3.9 8.o%
Example 4 55.9 3.8 8.o%
Examples 5 and 6 5-(4-chlorophenyl)-3-methylthio-1-phen~lpyrazole and 3-(4-chlorophenyl)-5-methylthio-1-phenxlpyrazole An inti~ate mixture of 1-(4-chlorophenyl)-3,3-bis(methyl-20 thio)-2-propen-1-one (5.2 g, 0.02 mole) and phenylhydrazine (2.2 g, 0.02 mole) was maintained at 165-170C for 4 hours. After cooling, the reaction mixture was dissolved in chloroform and the solution was washed with water and dried (MgS04). Evaporation of the dried solution afforded a crude mixture from which the pure isomeric title pyrazoles ~ere obtained by chromatography on silica gel using chloroform as eluant~ The first isomer el~ted was 3-(4-chlorophenyl)-5-methylthio-1-phenylpyrazole (yield 2.9 g, 49%, m.p. 56-58 C) followed by 5-(4-chlorophenyl)-3-methyl-thio-l-phenylpyrazole (yield 2.1 g, 35%, m.p. 66-69C).
30 A al~sis:
C H
Calculated for C16H13~1N2 63.9 4.3 9.3%
Found: Example 5 64.3 4.3 9.2%
Example 6 64.1 4.3 9.1%

s~

1o.
Example 7 5-(4-chlorophenyl)-3-ethylthio-1-phenylpyrazole An in-timate mixture of 1-(4-chlorophenyl)-3,3-bis(ethyl-thio)-2-propen-1-one (4.3 g, 0.015 mole) and phenylhydrazine (2.2 g, 0.020 mole) was maintained at 140-150C for 3 hours. After cooling, the reaction mixture was diRsolved in chloro~orm and the solution was washed with water and dried (MgS04). Evaporation of the dried chloroform solution afforded a crude mixture from which the pure 5-(4-chlorophenyl)-3-methylthio-1-phenylpyrazole was isolated (as the second major component) by chromatography on silica gel using chloroform as eluant. (Yield 0.9 g, 19%, m.p.
77-80C).
Analysis C H N
Calculated for C17H15ClN2S 64.9 4.8 8.9%
~ound 64.8 5.0 8.4%
Example 8 and 9 The ~ollowing compounds were prepared according to the procedure described in Examples 3 to 7.
3-(4-pyri_yl)-5-methylthio-1-phenylpyrazole Yield 29%, melting point 91-94 C.
Analysis C H
Calculated for C15H13N3S 67.4 4.9 15.7%
Found 66.6 4.8 15.6%
5-phenyl-3~methylthio-1-phen~lpyrazole Yield 24%, oil Analysis C H N
Calculated for C16H14N2S 72.2 5.3 10.5%
Found 71.5 5.5 9.9%
Example 10 3-(4-Chlorophenyl)-l-methyl-5-methylthiopyrazole A solution of 1-(4-chlorophenyl)-3,3-bis(methylthio)-2-propen-l-one (5.2 g, 0.02 mole) and methylhydrazine (0.9 g, 0.02 35S~

mole) in ethanol (50 ml) was heated under re~lux for 6 hours.
A~ter removing the solvent under reduced pressure, the residue was suspended in water and extracted with chloroform. Evap-oration of the dried (MgSO~) e~tract afforded the crude title pyrazole which was purified by chromatography on silica gel using chloroform as eluant. (Yield 4.0 g, 84% m.p. 53-56 C).
Analysis C H
Calculated f Cll 11 2 55 3 4.6 11.7%
Found 56.2 ~.6 11.8%
Examples 11 to 17 By procedures similar to those described in Example 10 the compounds in ~able I were prepared.

55~
12 .
__ ~ ~ ~ ~ ~ O~ D ~ O a\ o ~D
O O ~i r~ \~i N CU N ~ ~ i O
~; ~1 ~I r-i r~ ~1 ~1 ~1 ~I r~ ~1 ~J r~ .
~o ~o u~ o o ~ a~ o u~
_._ 0~ (~ r l \D r~ 11~ ~ N 0~ a~ CO
0 0 1~ Ll~ \C) ~ ~ ~ 0'~ 0~ (Y N O O
V ~ ~ u~ O U~
_ r~J ~r~ ~ ~ ~ ll:J
~u o Iv(L) ~) ~ a~
~q ~
rJ ~r~ ~ r~ r~
--l r~ r~ a r~ ~ r l ~ r~ ~ r~ ~
~ ~1 0 ~ O ~ O ~1 0 al O a:~ O a~ O
¢ ~ ~ V ~ V ~ V ~
___ U~
C~
~1 Z N N U~
~ N æ z u~ N U~ 0~
~i ~I rl h N Z ~Y) N
~ ~ v a:~ z 1~4 Z ~;
O O r~ r~ CU ~1 ~ _~
~4 p ~ X~ ~ r~ ~ ~ r~
~ V V C~ C~ V C~
_ _ ~ _ . , b~V
~ ~ ~ O r~ 0 H O ~ I ~ rl I N N
~ ~ p~ O U\ ~ 0 ¢ _ E~ ~
~rl U~ 0 Lf~ O ~ ~ r~
0 0 C~ CO CO 0 . - ~
~ I O I
~ r ~I r~ r~
3~ 0 ,5:t I ~ r~

I h ~ O ~ O ~ ,C
r~ I r~ rt ,~ r~ ~ r~ ,~ ~
o ~ ,q ~ ~ rOt ~ ~ ~ (IJ
,s~ rt ~ rt ,~ , t C) O S~ O O ~ u~ h ~ l O +~ cd rl ~1 0 r~ O ~ t ~
rd ,~ rt rq O rt r~ rt æ ~ ~ ?~
rt O +~ OtH ~ Z rt ,q ~ ~L~ ,q ~ J q ~ ~ 3 ~ r1 ~ rl ~ ~
rt C~ ~ ~ t ~ r1 ~ ' ' ' 53 S 5 ~i Example 18 5-(4-fluorophenyl)-3-methylthio-~=e~en~lpyrazole A solution of 1-(4-fluorophenyl)-3,3-bis(methylthio)-2-propen-1-one (1.2 g, 0.0050 mole) and phenylhydrazine (o.6 g, 0.0055 mole) in dry pyridine (20 ml) was heated under reflux for 18 hours. mhe reaction mixture was diluted with water, acidi~ied with dilute hydrochloric acid and extracted with chloroform. The extract was dried ~MgS04) and evaporated to yield a mixture of isomeric pyrazoles. The pure 5-(4-fluorophenyl)-3-methylthio-1-phenylpyrazole was separated by chromatography on silica gel, usin~ chloroform as eluant, as the second major component. (Yield o.6 g, 42%, m.p. 68-70C).
Analysis C H
Calculated for C16H13FN2S 67.6 4.6 9.9%
Found 67.8 4.7 9.5%
_ample 19 3-(4-chlorophenyl)-1-t-bu~yl-5-methylthiopyrazole Following a similar procedure to that in Example 18 the title pyrazole derivative was obtained.
Yield 96%, oil Analysis C H
Calculated for C14~17CI~2S 6.1 10.0%
Found 59.7 6.2 9.9%
Example 20 5-(4-chlorophenyl)-1-(4-fluorophenyl)-3-methylthiopyrazole A solution of 1-(4-chlorophenyl)-3,3-bis(methylthio)-2-propen-l-one (2.6 g, 0.010 mole) and 4-fluorophenylhydrazine ~ hydrochloride (1.8 g, 0.011 mole) in glacial acetic acid (25 ml) was heated under reflux for 3 hours. The reaction mixture was poured into cold water, basified with dilute sodium hydroxide and extracted with chloroform. The extract was dried (MgS04) and evaporated to yield a mixture of the title product and a small s~

14.
amount of its isomer. The isomers uere separated by chroma-tography on silica gel using chloroform as eluant. The pure 5-(4-chlorophenyl)-1-(4-fluorophenyl)-3-methylthiopyrazole which was the slower-running component, was obtained as an oil. (Yield 5 l.g g, 60%).
Analysis C H N
Calculated for C16H12ClFN2S 60.3 3.8 8.8%
Found 60.3 4 8.7%
10 Examples 21 and 22 ~ y a similar process to that used in Example 20 the ~ollow-ing were prepared.
5-(4-bromophenyl)-3 methylthio-l-methylpyrazole Yield 24%, oil.
15 Ana~2s~s C H N
Calculated for CllHllBrM2S 46.6 3.9 9.9%
E'ound 46.3 4.1 9.8%
5-(3,4-dichlorophen~ 3-methylthio-1-methylpyrazole Yield 28%, m.p. 48-51C
Analysis C H N
Calculated for C11HloC12N2S 48.4 3.7 10.3%
Found 49.0 3.8 10.3%
25 xamples 23 and 24 5-(4-chlorophenyl)-1-isobutyl-3-methylthiopyrazole and 3-(4-chloroph nyl)-1-isobutyl-5-methylthiop~razole Isobutyl bromide (2.3 g, 0.017 mole) was added to a stirred solution of 3(5)-(4-chlorophenyl)-5(3)-methylthiopyrazole ~2.3 g, 0.010 mole) and potassium hydroxide (o.6 g, 0.011 mole) in ethanol (50 ml). The reaction mixture was heated under reflux for 6 hours and then evaporated under reduced pressure. The residue was suspended in water and extracted with chloroform.
Evaporation of the dried (MgS04) extract afforded a mixture of 55~

the isomeric title compounds from which the pure ti-tle compounds were isolated by chromatography on silica gel using chloroform as eluant. The first compound eluted was 3-(4-chlorophenyl)-1-isobutyl-5-methylthiopyrazole (Yield l.l g, 3g%) followed by 5-(4-chlorophenyl)-1-isobutyl-3-methylthiopyrazole (Yield 0.4 g, 14%). 30th products are oils.
Analysis C H
Calculated for C14H17CI~2S 59 9 6.1 10.0%
Found: Example 23 59.7 6.o 10.1%
Example 24 60.3 6.3 10.0%
Examples 25 and 26 5-(4-chlorophenyl)-1-butyl-3-methylthiopyrazole and 3-(4-chlorophenyl)-1-butyl-5-methylthiopyrazole Butyl iodide (5.6 g, 0.03 mole) ~as added to a stirred solution of 3(5)-(4-chlorophenyl)-5(3)-methylthiopyrazole (4.6 g, 0.020 mole) and sodium hydroxide (1.2 g, 0.033 mole) in tetra-hydrofuran (50 ml). The reaction mixture was stirred under reflux for 15 hours and then evaporated under reduced pressure.
~he residue was suspended in water and extracted with chloroform.
Evaporated o$ the dried (MgS0~) extract yielded a crude mixture of the isomeric title compounds from which the puxe title com-pounds were obtained by chromatography on silica gel using chloro-form as eluant. The first compound eluted was 3-(4-chlorophenyl)-1-butyl-3-methylthiopyrazole. (Yield 2.1 g, 37%) followed by 5-(4-chlorophenyl)-1-butyl-3-methylthiopyrazole. (Yield 1.3 g, 23%) Analysis C H
Calculated for C14H17C1~2S 59.9 6.1 10.1%
Found: Example 25 58.8 6.o 10.1%
Example 26 60.3 6.2 9.8%
Example 27 3-(4-chlorophenyl)-1-ethyl-5-methylthiopyrazole Ethyl bromide (2.5 g, 0.023 mole) was added to a vigorously 16.
stirred water/methylene chloride emulsion (15 ml/25 ml) con-taining 3(5)-(4-chlorophenyl)-5(3)-methylthiopyrazole (4.6 g, 0.020 mole), sodium hydroxide (3.0 g, 0.075 mole) and tetra-t-butylammonium bromide (0.3 g) as phase-transfer catalyst. After 5 stirring for 6 hours at ambient temperature the oreanic phase was separated, washed with water and dried (MgS04). The residue obtained by evaporation of the dried extract was purified by chromatography on silica gel using chloroform as eluant. The pure title compound was isolated as an oil (3.5 g, 69%).
10 Analysis C H ~1 Calcul e 12 13 2 57 5.2 1l .1%
Found 56.9 5.3 11.0 Example_28 15 3-(4-chlorophenyl) l-(ethoxycarbonylmethyl)-5-methylthiopyrazole The title compound was prepared from 3-(5)-(4-chlorophenyl)-5-(3)-ethylthiopyrazole and ethylchloroacetate in a similar manner to that described in Example 27. (Yield 47%, melting point 64-67C).
20 Analysis C ~I N
Calculated for C14H15ClN202 54.1 4.8 9.0%
Found 54.2 4.8 9.1%
Example 29 25 3-(4-Chlorophenyl)-5-methylthio-1-prop~,rlpyrazole Propyl bromide (1.1 g, 0.009 mole) was added to a stirred suspension of the sodium salt of 3(5)-(4-chlorophenyl)-5(3)-methylthiopyrazole derived from the free base (1.8 g, 0.009 mole) and sodium hydride (0.25 g, 0.010 mole) in dry -tetrahydrofuran.
30 The reaction mixture was stirred under reflux for 6 hours a~d then left to cool overnight. The solvent was removed under reduced pressure and the residue was suspended in water and extracted with chloroform. Evaporation of the dried extract afforded an oily residue from which the pure title compound (1.1 17.
g, 52%) was isolated by chromatogr~phy on silica gel using chloroform as eluant. Traces of the isomer, 5-(4-chlorophenyl)-3 methylthio-l-propylpyrazole were detec-ted in the crude product but pure material was not isolated.
5 Analysis C H
Calculated for C13H15ClN2S 58-5 5.6 10.5%
Found 5 5 5.6 10.6%
3xam~ 30 5-(4-chlorophenyl ? -3-methylthio-1-methylpyrazole The reaction between the sodium salt of 3(5)-(4-chloro-phenyl!-5(3)-methylthiopyrazole and methyl iodide under similar conditions to those in Example 29 gave a mixture of 3-(4-chlor-ophenyl)-5-methylthio-1-methylpyrazole (see Example 10 above) 15 (42% isolated yield) ana 5-(4-chlorophenyl)-3-methylthio-1-methylpyrazole (34% isolated yield).
Analysis C H N
Calculated f r Cll 11 2 55 4.6 11.7%
Found 55. 6 4.8 11.7%
The insecticidal, acaricidal and acarid ovicidal activity of the pesticidal pyrazole derivatives according to the present invention was assessed in the manner described in Examples 31 to 33 inclusive. In each case the approximate LC50's were obtained and are expressed as toxicity grades as follows:
LC (~ active material in spray) Toxicit~ grade > o.6% o ~ o.6 and > 0.2 ~ 0.2 and ~ o.o6 2 ~ o.o6 and ~ 0.02 3 0.02 and ~ o.oo6 4 o . oo6 5 Results of the tests in each of the Examples are given in Table II in which the pest is identified by its initial letters.

18.
Example 31 The insecticidal activity of the compounds of the invention was assessed using black bean aphids (Aphis fabae) (A.f.) by the following procedure.
Pairs of leaves were removed from broad bean plants and placed on filter paper inside plastic petri dishes. The leaves were sprayed on the under-surface with an aqueous formulation containing 20% by weight of acetone, 0.05~ by weight of TRITON X-100 (Trade Mark) as wetting agent and 0.4% b~ weight of the co~pound to be tested. Varying concentrations were obtained by diluting the formulation. After spraying, the leaves were left to dry for ~-1 hour and each leaf pair was infested with ten adult aphids (Aphis fabae). After twenty four hours the percent-ages of dead and moribund aphids were recorded.
Example 32 The acaricidal activity of the pesticidal pyrazole deri-vatives according to the invention was assessed on glasshouse red spider mite, Tetranychus urticae (T.u.).
Discs were cut ~rom the leaves of French bean plants and were placed on filter paper kept moist by a cotton-wool wick dipping into water. Each disc was infested wi-th ten adult mites and the aiscs were then sprayed with a solution or suspension of the test compound in acetone-water (20:80) containing 0.05% of ~RITO~ X-100 (Trade Mark) as wetting agent. After 2~ hours the percentage of dead and moribund mites was assessed.
E~ample 33 Acarid ovicidal activity was tested using eggs of the glasshouse red spider mite, Tetranychus urticae (T.u. Ov.).
Glasshouse spider mites were reared on French bean plants and held on filter paper kept moist by a cotton wool wick dipping into water in a cream carton. Each leaf was infected with 10 adult mites and after 24 hours the mites were removed and the number of eggs laid was counted with the aid of a low power binocular microscope. On average, 70 eggs were laid on each 35i51~

19.
disc.
The discs were then sprayed with a solution or suspension of the test compound.is acetone/water (20:80) containing 0.05% of TRITON X-100 (Trade Mark), a surface-active agent. A dosage equivalent to 340 litres/hectare was applied.
After 7 days under glasshouse conditions (23C - 2C, fluctuating humidity and light), the numbers of hatched nymphs and unha-tched eggs were coun-ted and the percentage mortali-ty calculated.
TABLE II

Example Pesticidal Activity Example Pesticidal Activity ~ A = I = ~ u Ov ~o. A.f. T.u. T.u.Ov. .

6 1 2 3 20 O 0 3

7 O 0 5 21 0 3 3

8 0 2 3 22 2 3 )~

9 2 2 4 23 1 2 5 .

Claims (8)

20.

1. A pyrazole derivative of general formula:- (I) wherein R1 represents a phenyl, pyridyl or naphthyl group optionally substituted by one or more substituents selected from halogen, cyano, amino, and mono- and di(C1-4 alkyl)-amino; R2 represents a phenyl group, a fluorophenyl group or a C1-6 alkyl group optionally substituted by a (C1-6 alkoxy)-carbonyl group; and R3 represents a methyl or ethyl group, excluding 3-phenyl-5-methylthio-1-phenyl-pyrazole.

2. A pyrazole derivative according to claim 1 wherein R1 is a phenyl group optionally substituted by one or two halogen atoms; or, when R2 is a C1-6 alkyl group optionally substit-uted by a (C1-6 alkoxy)carbonyl group, a dimethylaminophenyl group or a naphthyl group; or, when R2 represents a phenyl or fluorophenyl group, a pyridyl group.

3. A pyrazole derivative according to claim 1 wherein R1 represents a phenyl group optionally substituted at the 3-and/or 4-positions by fluorine, chlorine or bromine, or at the 4-position by a dimethylamino group; a 4-pyridyl group or 2-naphthyl group.

21.

4. A pyrazole derivative according to claim 1 wherein R2 represents a phenyl group, a fluorophenyl group, a C1-4 alkyl group or an ethoxycarbonylmethyl group.

5. A pyrazole derivative according to any one of claims 1, 3 and 4 wherein the carbon atom to which the group -SR3 is attached is at the 3-position in the pyrazole ring.

6. A pyrazole derivative according to Claim 1 wherein R1 is a phenyl group substituted at the 4-position by a fluorine, chlorine or bromine atom, R2 is phenyl group or a 2-methyl-propyl group, R3 is a methyl or ethyl group and the carbon atom to which the group -SR3 is attached is at the 3-position in the pyrazole ring.

7. A process for preparing a pyrazole derivative as defined in claim 1 which comprises reacting a compound of general formula:- (II) wherein R1 and R3 are as defined in claim 1, with a compound of general formula:-R4NH-NH2 (III) or an acid-addition salt thereof wherein R4 is R2 as defined in claim 1 or hydrogen, followed when R4 is hydrogen by reacting the resulting compound with a compound of general formula R5X, wherein R5 is an optionally substituted alkyl group and X is a halogen atom, to produce a compound of formula I wherein R2 is R5.

8. A method of combating pests at a locus which comprises applying to that locus a compound according to any one of claims 1 to 3.