1-pesticidal 1-arylpyrazoles

Pesticide 1-arylpyrazole {PESTICIDAL 1-ARYLPYRAZOLES}

The present invention relates to novel 1-arylpyrazolecarboxaldehyde oximes, compositions and derivatives thereof. The present invention relates to their unexpectedly useful systemic insecticidal action. The present invention relates in particular to compositions and methods of control of said compounds for controlling arthropods, nematodes, parasites or protozoa using said compositions. In particular, the present invention relates to the agricultural application of said compounds or compositions to control arthropods, in particular insects by action on the whole, in particular as insecticides. The present invention also relates to 1-arylpyrazole hydrazone.

Control of insects, nematodes or parasites by active substances having 1-arylpyrazole groups has been described in a number of patents or patent applications, such as International Patent Publication No. WO 93/06089 (and equivalent U.S. Patent No. 5,451,598), WO 94/21606 and WO 87/03781 as well as European Patent Publications 0295117, 659745, 679650, 201852 and 412849, German Patent 19511269 and US Patent 5,232,940.

Other compounds are disclosed in WO 92/13451 (August 20, 1992, Schering Agrochemical Ltd.,), 5-chloro-1-[2,6- having inhibitory activity against the single species Lucilia sericata (sleep blow fly). Dichloro-4-(trifluoromethyl)phenyl]-4-(4,5-dicyano-1H-imidazol-2-yl)-3-hydroxyiminomethyl-1H-pyrazole is described as an intermediate .

This Schering mentions only 1-arylpyrazole-oxime compounds as pesticides.

An object of the present invention relates to a novel pesticidal compound of 1-arylpyrazole-based compounds and a method for preparing them.

A second object of the present invention is the use of insecticidal pyrazole compounds to control arthropods, especially insects, plant nematodes, or parasites or protozoa, especially in agricultural or horticultural crops, forestry, veterinary or dairy farming, or public health. It relates to pesticidal compositions and pesticidal methods.

A third object of the present invention is a highly active compound having a broad-spectrum insecticidal action, and a selective specific action, such as aphid, insecticidal action on leaves, insecticidal and nematicidal action on soil, and a systemic action, seed, It relates to a compound that exhibits growth inhibition or insecticidal action through treatment.

A fourth object of the present invention relates to compounds which exhibit substantially improved and faster inhibitory activity, particularly against insects, more particularly against insects in the larval state.

A fifth object of the present invention is to improve the transport of compounds to the site of action against pests, due to their high permeability to pest species when applied topically.

Another object of the present invention is to provide compounds with improved action and increased stability for users and the environment.

These objects of the present invention will become clear from the following detailed description. These objects correspond in whole or in part to the present invention.

The present invention relates to a novel chemical composition having a systemic action, and a method for treating plants with a novel chemical composition having an insecticidal or nematicidal systemic action of the formula (I), geometric isomers, tautomeric forms and pesticidal active salts thereof will be :

<chemistry id="i"><img file="KR20000062320A_D0001.tif" /></chemistry>

[In the above formula,

X is -S(O)_mR₆ or R₇ ego,

Y is hydrogen, C_3-6 Alkenyl, alkynyl, formyl, alkylcarbonyl, cycloalkylcarbonyl, halocycloalkyl carbonyl, aroyl, arylalkylcarbonyl, alkylsulfonyl, arylsulfonyl, haloalkylcarbonyl, aminoalkylcarbonyl, Alkylaminoalkylcarbonyl, dialkylaminoalkylcarbonyl, alkoxyalkylcarbonyl, aryloxyalkylcarbonyl, alkylthioalkylcarbonyl, alkylsulfonylalkylcarbonyl, arylthioalkylcarbonyl, N-alkylcarbamoyl, N-arylcarbamoyl, N-alkylthiocarbamoyl, N-arylthiocarbamoyl, alpha-hydroxyarylalkylcarbonyl, hydroxyalkylcarbonyl, carboxyalkylcarbonyl, alkoxycarbonylalkylcarbonyl, -P(=O)(O-alkyl)₂, -P(=S)(O-alkyl)₂, -P(=O)(S-alkyl)₂, -P(=S)(S-alkyl)₂, trialkylsilyl, alkylcarbonylaminoalkylcarbonyl, alkylcarbonyloxyalkylcarbonyl, aryl, pyridinyl, pyrimidinyl, -C(=O)S-alkyl, -C(=O)S-aryl, -C(=O)S-alkylaryl, alkoxyalkoxycarbonyl, alkylthioalkoxycarbonyl, alkylsulfonylalkoxycarbonyl, arylthioalkoxycarbonyl, alkoxycarbonyl, aryloxycarbonyl and aryloxycarbonylalkylcar bonyl; or alkoxy, alkoxycarbonyl, carboxy, cyano, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkylthio, nitro, alkylsulfinyl, alkylsulfonyl, alkylcarbonyl, amino, alkylamino, di alkyl or haloalkyl optionally substituted with alkylamino, hydroxy, alkylcarbonylamino or alkylcarbonyloxy;

Z is hydrogen, halogen, -C(O)R₇-, -S(O)_nR₈, -C(O)OR₉, alkyl, haloalkyl, -OR₉, -N=C(R₁₀)(R₁₁), alkenyl, hydrazino, alkylthiocarbonyl, 1H-pyrrol-1-yl or 1H-pyrazol-1-yl,

-CHO, -CH=NOH, amino, R₁₂NH- or R₁₃R₁₄N-;

R₁ is hydrogen, alkyl or -NR₁₅R₁₆ ;

R₂ is hydrogen or halogen;

R₃ and R₅ is hydrogen, halogen or alkyl;

R₄ is halogen, haloalkyl, haloalkoxy, R₁₇S(O)_p-or SF₅ ;

R₆ silver C_3-5 alkyl or haloalkyl, alkenyl or haloalkenyl, alkynyl or haloalkynyl or cycloalkyl;

R₇ is alkyl or haloalkyl;

R₈ silver R₇ or phenyl;

R₉ and R₁₀ is hydrogen, alkyl or haloalkyl;

R₁₁ is alkyl, haloalkyl, alkoxy, or hydroxy, halogen, alkoxy, cyano, R₇ or -S(O)_qR₇ a phenyl group optionally substituted with one or more groups selected from;

R₁₂, R₁₃ and R₁₄ is the same or different, R₇S(O)_r-, formyl, alkynyl, alkoxycarbonyl, alkylthiocarbonyl or aroyl; or alkyl, C_3-6 alkenyl or -C(O)alkyl (alkyl and alkenyl are at least one R₁₈ optionally substituted with) ; or R₁₃ and R₁₄ are joined together to form a divalent radical having 4 to 6 atoms in the chain, the divalent radical being alkylene, alkyleneoxyalkylene or alkyleneaminoalkylene, preferably morpholine, pyrrol forming a din, piperidine or piperazine ring;

R₁₅ and R₁₆ is hydrogen or alkyl, respectively;

R₁₇ silver haloalkyl;

R₁₈ is cyano, nitro, alkoxy, haloalkoxy, -C(O)R₇, R₈S(O)_s-, -C(O)OR₉, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, halogen, hydroxy, aminosulfonyl, alkylaminosulfonyl or dialkylaminosulfonyl;

m, n, p, q, r and s are 0, 1 or 2;

M is C-halo, C-CH₃, C-CH₂F, C-CH₂Cl, C-NO₂, or N].

The term "insecticidally acceptable salts" means salts of anions and cations known and accepted in the art for the formation of pesticidally acceptable salts. Preferably, the salts are water-soluble. The above formula containing an amine group Suitable acid addition salts formed from compounds of formula I include inorganic acid salts such as hydrochloride, phosphate, sulfate and nitrate, and organic acid salts such as acetate Suitable base addition salts formed from compounds of formula I containing a carboxylic acid group Examples include alkali metal (eg sodium or potassium) salts, ammonium salts and organic amine (eg diethanolamine or morpholine) salts.

R₁ this -nr₁₅R₁₆ (wherein, R₁₆ is hydrogen and R₁₅ is hydrogen or alkyl) may exist in the form of a tautomer represented by the following formulas Ia and Ib. The tautomer phenomenon is described in The Chemistry of Functional Groups: Amidines and Imidates, Vol 2, 1991, p. 276-277] (S. Patai). All such tautomeric forms are encompassed by the present invention.

<img file="KR20000062320A_D0002.tif" />

If, alternatively, certain alkyl, alkoxy and alkylthio groups have 1 to 6 (preferably 1 to 4) carbon atoms, then the alkenyl group has 2 to 6 (preferably 2 to 4) carbon atoms. of carbon atoms, and the alkynyl group has 3 to 6 (preferably 3 to 4) carbon atoms. Cycloalkyl groups have 3 to 8, preferably 5 to 7 carbon atoms. The term "aryl" means a mono or polycyclic aromatic moiety, preferably including phenyl, pyridyl, pyrimidinyl, furyl and naphthyl groups. Formed by a divalent alkylene radical in combination with a nitrogen atom It will be understood that rings are usually 5, 6 and 7-membered rings In the context of the present invention, several terms are used in their specific meaning: "aminocarbonyl" )NH₂ means a radical of Similarly, "alkylaminocarbonyl"means an alkylcarbamoyl radical, i.e. a radical of the formula -C(O)-NH-alkyl; "dialkylaminocarbonyl"is a dialkylcarbamoyl radical; i.e. the formula -C(O)-N(alkyl)₂ of (wherein the alkyl moieties may be the same or different). "Aminosulfonyl" is a sulfamoyl radical, i.e. -SO₂NH₂ means Similarly, "alkylaminosulfonyl" refers to an alkylsulfamoyl radical, i.e. the formula -SO₂means a radical of NH-alkyl; "Dialkylaminosulfonyl"is the formula -SO₂N (alkyl)₂ (wherein the alkyl moieties may be the same or different) means a dialkylsulfamoyl radical having

"Halo" before the name of a radical means that the radical has been partially or fully halogenated, i.e. substituted with F, Cl, Br or I, preferably F or Cl. "Halogen" means F, Cl, Br or I. When the names of arbitrary substituents are repeated, the same meaning is maintained unless otherwise specified. "arol"means a carbonyl aromatic radical, ie aryl-C(0)-, which is preferably benzoyl which may be substituted with one or more alkyl, alkoxy or halogen groups.

Z is amino, R₁₂NH- or R₁₃R₁₄N-phosphorus compounds are preferred.

X is -S(O)_mR₆ Phosphorus compounds are preferred.

R₁ is preferably amino or hydrogen;

R₆ is preferably alkyl, particularly preferably methyl and ethyl;

R₃ and R₅is preferably hydrogen;

R₄ is preferably haloalkyl, haloalkoxy or SF₅, particularly preferably trifluoromethyl;

M is preferably C-halo or N;

Y is preferably hydrogen or alkoxycarbonyl.

R of Formula I₂ to R₅ and a preferred phenyl group or pyridyl group comprising an M radical is 2,6-dichloro-4-trifluoromethylphenyl; 2,6-dichloro-4-trifluoromethoxyphenyl; 2-bromo-6-chloro-4-trifluoromethylphenyl; 2-bromo-6-chloro-4-trifluoromethoxyphenyl; 2,6-difluoro-4-trifluoromethylphenyl; 2-chloro-4-trifluoromethylphenyl; 3-chloro-5-trifluoromethyl-2-pyridinyl; 3-chloro-5-trifluoromethoxy-2-pyridinyl; 2-bromo-6-fluoro-4-difluoromethylphenyl; 2-chloro-6-fluoro-4-trifluoromethylphenyl; 2,6-dibromo-4-trifluoromethylphenyl; 2,6-dibromo-4-trifluoromethoxyphenyl; and 2,6-dichloro-4-pentafluorothiophenyl.

Preferred classes of compounds of formula (I) are those having the following properties:

X is -S(O)_mR₆ ego ;

Y is hydrogen; C which may be substituted with aminocarbonyl, alkylsulfonyl, alkoxy, alkoxycarbonyl, alkylcarbonyl, cyano or nitro₁-C₄ alkyl (including linear, branched and cyclic); C₃-C₄ alkenyl; C₃-C₅ alkynyl; alkyl carbonyl; aroyl which may be substituted; arylalkylcarbonyl; alkylsulfonyl; alkoxycarbonylalkylcarbonyl; haloalkylcarbonyl; N-alkylcarbamoyl; alkoxycarbonyl; aryloxycarbonyl; alkoxyalkyl carbonyl; alpha-hydroxyarylalkylcarbonyl; hydroxyalkyl carbonyl; aminoalkyl carbonyl; -C(=O)S-alkyl and trialkylsilyl;

Z is amino, R₁₂NH-, R₁₃R₁₄N-, halogen or methyl;

R₁ is hydrogen, methyl, amino or methylamino;

R₂ is F, Cl, Br or H;

R₃ and R₅is hydrogen;

R₄ is CF₃, CF₃O, CHF₂, CF₃S(O)_p, CF₂Cl, CFCl₂, CF₂ClO, CFCl₂O, Cl, Br or F;

R₆ is methyl or ethyl which may be substituted with F, Cl or Br;

M is CCl, CF, CBr or N;

R₁₂, R₁₃ and R₁₄ is CF₃S(O)_r-, alkynyl or alkoxycarbonyl; or the alkyl and alkenyl moieties are at least one R₁₈ Alkyl which may be substituted with, C₃-C₆ alkenyl or -C(O)alkyl;

R₁₈ is cyano, nitro, alkoxy, haloalkoxy, -C(O)R₇, R₈S(O)_s-, -C(O)OR₉, aminocarbonyl, alkylaminocarbonyl, halogen, hydroxy, aminosulfonyl, alkylaminosulfonyl or dialkylaminosulfonyl.

Another preferred class of compounds of formula (I) are those having the following properties:

Y is halogen; C which may be substituted with cyano, carbamoyl, carboxy, alkoxycarbonyl, alkylthio, alkylsulfinyl or alkylsulfonyl₁-C₃ an alkyl group; trialkylsilyl; acetyl; propionyl which may be substituted with alkoxycarbonyl; benzoyl optionally substituted with alkyl; alkoxycarbonyl; or N-alkylcarbamoyl;

Z is amino, R₁₂NH-, R₁₃R₁₄N-, -CHO, -CH=NOH, halogen or methyl;

R₁ is hydrogen, methyl, amino or methylamino;

R₂ is chlorine, bromine or hydrogen;

R₃ and R₅is hydrogen;

R₄ is CF₃ or OCF₃ is ;

R₆ may be substituted with methyl or ethyl halide;

R₇ silver CF₃ is ;

R₁₂, R₁₃ and R₁₄ is alkynyl; or R₈S(O)_s-, methyl or ethyl which may be substituted with cyano or aminocarbonyl;

R₈ is alkyl or phenyl;

M is C-Cl, C-Br or N.

According to another aspect of the present invention, Y may be a sugar moiety. Preferably, Y is a ring containing 4, 5 or 6 carbon atoms and interrupted by 1 oxygen atom. In this case, the carbon atom is at least one hydroxyl group, at least one CH₂substituted with an OH group or one or more OC(O)alkyl groups.

The present invention also provides an arylpyrazole of formula I bis, or a pesticidally acceptable salt thereof:

<chemistry id="i비스"><img file="KR20000062320A_D0003.tif" /></chemistry>

In the above formula,

A is -NR₂₆- ego ;

Y₁ is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, -S(O)_aR₂₈, -P(O)R₂₉R₃₀, -P(S)R₂₉R₃₀, -Si(R₃₁)(R₃₂)(R₃₃), -C(O)R₂₇, -C(S)R₂₇, cyano or nitro;

R₁₉ is hydrogen, alkyl, haloalkyl or -NR₃₄R₃₅ ego ;

R₂₀ Silver -S(O)_bR₃₆ or R₃₇ is ;

R₂₁ is hydrogen, halogen, -C(O)R₃₈, -S(O)_cR₃₉, alkyl, haloalkyl, -OR₄₀, -N=C(R₄₁)(R₄₂), alkenyl, -NR₄₃R₄₄, 1H-pyrrol-1-yl, 1H-pyrazol-1-yl or CH=NOH;

R₂₂, R₂₃ and R₂₅ each is selected from hydrogen, halogen or alkyl;

R₂₄ is halogen, haloalkyl, haloalkoxy, -S(O)_dR₄₅ or SF₅ ego ;

R₂₆ is hydrogen or substituted or unsubstituted alkyl;

R₂₇ is hydrogen, substituted or unsubstituted C₁-C₂₀ Alkyl, substituted or unsubstituted aryl, -OR₄₆, -NR₄₇R₄₈ or -SR₄₉ ego ;

R₂₈ is substituted or unsubstituted alkyl or substituted or unsubstituted aryl;

R₂₉ and R₃₀ are each selected from alkoxy and thioalkoxy;

R₃₁, R₃₂ and R₃₃ are each selected from alkyl, haloalkyl and aryl;

R₃₄ and R₃₅ each is selected from hydrogen or substituted or unsubstituted alkyl;

R₃₆ is alkyl, alkenyl, alkynyl or C which may be substituted with one or more halogen₃-C₆ cycloalkyl;

R₃₇ is alkyl or haloalkyl;

R₃₈ is hydrogen, alkyl, haloalkyl, alkoxy or thioalkoxy;

R₃₉ is alkyl, haloalkyl or aryl;

R₄₀ and R₄₁ are each selected from hydrogen, alkyl and haloalkyl;

R₄₂ is hydroxy, halogen, alkoxy, -CN, alkyl, -S(O)_ealkyl, haloalkyl, alkoxy or phenyl which may be substituted with one or more groups selected from alkyl;

R₄₃ and R₄₄ are hydrogen and NH, respectively₂, -S(O)_fR₅₀, -C(O)R₅₁, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl and alkynyl; or the two together may form a divalent alkylene radical which may be interrupted by one or more heteroatoms, preferably selected from oxygen, nitrogen and sulfur;

R₄₅ is haloalkyl;

R₄₆ and R₄₉ are each selected from substituted or unsubstituted alkyl and substituted or unsubstituted aryl;

R₄₇ and R₄₈ are each selected from hydrogen, substituted or unsubstituted alkyl and substituted or unsubstituted aryl; or the two together may form a divalent alkylene radical which may be interrupted by one or more heteroatoms, preferably selected from oxygen, nitrogen and sulfur;

R₅₀ is substituted or unsubstituted alkyl;

R₅₁ is hydrogen, alkyl, haloalkyl, aryl, alkenyl, -OR₅₂, -SR₅₃ or -NR₅₄R₅₅ ego ;

R₅₂ and R₅₃ are each selected from alkyl and haloalkyl;

R₅₄ and R₅₅ are each selected from hydrogen, alkyl, haloalkyl and aryl;

a, b, c, d, e and f are each 0, 1 or 2;

M₁ is C-halo, C-CH₃, C-CH₂F, C-CH₂Cl, C-NO₂ or N.

Preferred compounds of the formula I bis are those having one or more of the following characteristics:

A is -NR₂₆- ego ;

Y₁ is hydrogen, alkyl or -C(O)R₂₇ is ;

R₁₉ is hydrogen or NH₂ ego ;

R₂₀ Silver -S(O)_bR₃₆ is ;

R₂₁ silver -NR₄₃R₄₄ ego ;

R₂₂ is halogen;

R₂₃ and R₂₅ is hydrogen;

R₂₄ is haloalkyl;

R₂₇ is alkyl or O-alkyl; or

M is C-halo.

Another preferred class of compounds of the formula I bis are those having the following characteristics:

A is -NR₂₆- ego ;

Y₁ is hydrogen, alkyl or -C(O)R₂₇ is ;

R₁₉ is hydrogen or NH₂ ego ;

R₂₀ Silver -S(O)_bR₃₆ is ;

R₂₁ silver -NR₄₃R₄₄ ego ;

R₂₂ is halogen;

R₂₃ and R₂₅ is hydrogen;

R₂₄ is haloalkyl;

R₂₇ is alkyl or O-alkyl;

M is C-halo.

For the compounds of formula I bis, the term "substituted" is preferably halogen, hydroxy, alkylthio, cyano, carboxy, -C(O)alkyl, -C(O)Oalkyl, -C (O)NH₂, -C(O)NHalkyl, -C(O)N(alkyl)₂In , aryl, nitro, azido, amino, alkylamino, dialkylamino, alkylsulfenyl, alkylsulfinyl, alkylsulfonyl, aryloxy, arylthio, alkylcarbonylamino, alkylcarbonyloxy or aryloxycarbonyl It means substituted with one or more substituents selected.

Among the compounds of the formula (I) or (I) bis, the following compounds which particularly usefully inhibit insect species by systematic action are particularly preferred. The numbers of compounds are for reference only.

1) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde oxime

2) 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-ethylamino-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde oxime

3) 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-methylamino-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde oxime

4) 5-amino-1-[2,6-dichloro-4-(trifluoromethoxy)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde oxime

5) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfinyl-1H-pyrazole-3-carboxaldehyde oxime

6) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-trifluoromethylthio-1H-pyrazole-3-carboxaldehyde oxime

7) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-difluoromethylthio-1H-pyrazole-3-carboxaldehyde oxime

8) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylthio-1H-pyrazole-3-carboxaldehyde oxime

9) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-trifluoromethylthio-1H-pyrazole-3-carboxaldehyde O-(methyl)oxime

10) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde O-(acetyl)oxime

11) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde O-(2-methylbenzoyl) oxime

12) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde O-(methoxycarbonyl) oxime

13) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde O-[2-(ethoxy) carbonyl) propionyl] oxime

14) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylthio-1H-pyrazole-3-carboxaldehyde O-(acetyl)oxime

15) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylthio-1H-pyrazole-3-carboxaldehyde O-(methoxycarbonyl)oxime

16) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfonyl-1H-pyrazole-3-carboxaldehyde oxime

17) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde O-(methyl)oxime

18) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde O-(N-methylcarba Moil) oxime

19) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde O-(carboxymethyl)oxime

20) 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde oxime

21) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde O-(tert-butyldimethylsilyl ) oxime

22) 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-formyl-N-hydroxy-4-trifluoromethylthio-1H-pyrazole-3-carboximide amides

23) 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-5-hydroxyiminomethyl-4-trifluoromethylthio-1H-pyrazole-3-car boximidamide

24) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde O-(isopropyl)oxime

25) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde O-(ethoxycarbonylmethyl ) oxime

26) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde O-(aminocarbonylmethyl) oxime

27) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde O-[2-(ethylsulf) phonyl) ethyl] oxime

28) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde O-(2-cyanoethyl ) oxime

29) 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-methyl-4-methylthio-1H-pyrazole-3-carboxaldehyde oxime

30) 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-methyl-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde oxime

31) 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-methyl-4-methylsulfonyl-1H-pyrazole-3-carboxaldehyde oxime

32) 5-amino-1-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde oxime

33) 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-ethylthio-5-methyl-1H-pyrazole-3-carboxaldehyde oxime

34) 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfinyl-5-methyl-1H-pyrazole-3-carboxaldehyde oxime

35) 1-[2-chloro-4-(trifluoromethyl)phenyl]-5-[2-ethylsulfonyl(ethylamino]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde oxime

36) 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-dimethylamino-4-methylthio-1H-pyrazole-3-carboxaldehyde oxime

37) 5-amino-1-[2,6-dichloro-4-(trifluoromethoxy)phenyl]-4-ethylsulfinyl-1H-pyrazole-3-carboxaldehyde oxime

38) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-trifluoromethyl-1H- pyrazole-3-carboxaldehyde oxime

39) 3-Acetyl-5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole oxime

40) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-trifluoromethylsulfinyl-1H-pyrazole-3-carboximide amides

41) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-methoxy-4-trifluoromethylsulfinyl-1H-pyrazole-3-carboximide amides

42) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-ethylsulfinyl-1H-pyrazole-3-carboximidamide

43) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-ethylthio-1H-pyrazole-3-carboximidamide

44) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-methylsulfinyl-1H-pyrazole-3-carboximidamide

45) 5-amino-1-[2,6-dichloro-4-(trifluoromethoxy)phenyl]-N-hydroxy-4-methylsulfinyl-1H-pyrazole-3-carboximidamide

46) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-methylsulfonyl-1H-pyrazole-3-carboximidamide

47) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-methylthio-1H-pyrazole-3-carboximidamide

48) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-ethylsulfonyl-1H-pyrazole-3-carboximidamide

49) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-methoxy-4-methylsulfinyl-1H-pyrazole-3-carboximidamide

50) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-methoxy-N-methyl-4-methylsulfinyl-1H-pyrazole-3-car Voximidamide

51) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-(2-fluoroethylsulfinyl)-1H-pyrazole-3- Carboximidamide

52) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-(2-fluoroethylsulfonyl)-1H-pyrazole-3- Carboximidamide

53) 5-amino-1-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]-4-ethylsulfinyl-N-hydroxy-1H-pyrazole-3-carboximidamide

54) 5-amino-1-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]-4-methylsulfinyl-N-hydroxy-1H-pyrazole-3-carboximidamide

55) 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-5-methylamino-4-methylsulfinyl-1H-pyrazole-3-carboximidamide

56) 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-ethylamino-N-hydroxy-4-methylsulfinyl-1H-pyrazole-3-carboximidamide

57) 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[2-(ethylsulfonyl)ethylamino]-N-hydroxy-4-methylsulfinyl-1H-pyra Sol-3-carboximidamide

58) 5-[2-(cyano)ethylamino]-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-methylsulfinyl-1H-pyrazole -3-carboximidamide

59) 5-(aminocarbonylmethylamino)-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-methylsulfinyl-1H-pyrazole-3- Carboximidamide

60) 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-5-[2-phenylsulfonyl)ethylamino]-N-hydroxy-1H-pyrazole -3-carboximidamide

61) 5-amino-1-[2,6-dibromo-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-hydroxy-1H-pyrazole-3-carboximidamide

62) 1-[2-bromo-6-chloro-4-(trifluoromethyl)phenyl]-5-ethylamino-4-methylsulfinyl-N-hydroxy-1H-pyrazole-3-carboxy midamide

63) 5-amino-1-[2-bromo-6-chloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-hydroxy-1H-pyrazole-3-carboximide amides

64) 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfinyl-5-[2-(methylsulfinyl)ethylamino]-N-hydroxy-1H-pyra Sol-3-carboximidamide

65) 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-5-[2-(methylsulfinyl)ethylamino]-N-hydroxy-1H-pyra Sol-3-carboximidamide

66) 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfinyl-5-[2-(ethylsulfinyl)ethylamino]-N-hydroxy-1H-pyra Sol-3-carboximidamide

67) 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-5-[(prop-2-ynyl)amino]-N-hydroxy-1H-pyra Sol-3-carboximidamide

68) 5-Amino-1-[2-chloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-hydroxy-1H-pyrazole-3-carboximidamide.

Other compounds of Formula I or I bis provided herein include:

69) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-amino-1H-pyrazole-3-carboximidamide;

70) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(isopropylcarbonyl)amino-1H-pyrazole-3-carboxy midamide;

71) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(n-heptylcarbonyl)amino-1H-pyrazole-3- carboximidamide;

72) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(ethoxycarbonyl)amino-1H-pyrazole-3-carboxy midamide;

73) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-trifluoromethylsulfinyl-N-amino-1H-pyrazole carboximidamide;

74) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfinyl-N-amino-1H-pyrazole carboximidamide;

75) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-trifluoromethylsulfinyl-N-acetylamino-1H-pyrazole carboximidamide;

76) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(1-methylethenylcarbonylamino)-1H-pyrazole carboxy midamide;

77) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(tert-butylcarbonylamino)-1H-pyrazole carboximidamide ;

78) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(2-methylethenylcarbonylamino)-1H-pyrazole carboxy midamide;

79) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(ethylcarbonylamino)-1H-pyrazole carboximidamide;

80) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-propylcarbonylamino)-1H-pyrazole carboximidamide;

81) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(1-ethylpropylcarbonylamino)-1H-pyrazole carboximida mid;

82) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(butylcarbonylamino)-1H-pyrazole carboximidamide;

83) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(pentylcarbonylamino)-1H-pyrazole carboximidamide;

84) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(hexylcarbonylamino)-1H-pyrazole carboximidamide;

85) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfinyl-N-acetylamino-1H-pyrazole carboximidamide;

86) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-chloroacetylamino-1H-pyrazole carboximidamide;

87) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(tridecylcarbonylamino)-1H-pyrazole carboximidamide;

88) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(n-propoxycarbonylamino)-1H-pyrazole carboximida mid;

89) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(1,1-dimethylpropyloxycarbonylamino)-1H-pyra sol carboximidamide;

90) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(tert-butyloxycarbonylamino)-1H-pyrazole carboximida mid;

91) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(acetyloxy)-1H-pyrazole carboximidamide;

92) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl-1-ethylsulfinyl-N-(acetyloxy)-1H-pyrazole carboximidamide;

93) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(ethylcarbonyloxy)-1H-pyrazole carboximidamide;

94) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(propylcarbonyloxy)-1H-pyrazole carboximidamide;

95) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(2-methylethenylcarbonyloxy)-1H-pyrazole carboxy midamide;

96) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(benzoyloxy)-1H-pyrazole carboximidamide;

97) 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-methylamino-4-methylsulfinyl-N-(acetyloxy)-1H-pyrazole carboximidamide;

98) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfonyl-N-(acetyloxy)-1H-pyrazole carboximidamide;

99) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl-1-methylsulfinyl-N-(heptylcarbonyloxy)-1H-pyrazole carboximidamide;

100) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl-1-methylsulfonyl-N-(heptylcarbonyloxy)-1H-pyrazole carboximidamide;

101) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfenyl-N-(acetyloxy)-1H-pyrazole carboximidamide;

102) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfenyl-N-(heptylcarbonyloxy)-1H-pyrazole carboximidamide;

103) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-trifluoromethylsulfinyl-N-(acetyloxy)-1H-pyrazole carboximidamide;

104) 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-formylamino-4-ethylsulfenyl-N-(acetyloxy)-1H-pyrazole carboximidamide;

105) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(hexylcarbonyloxy)-1H-pyrazole carboximidamide;

106) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(pentylcarbonyloxy)-1H-pyrazole carboximidamide;

107) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(butylcarbonyloxy)-1H-pyrazole carboximidamide;

108) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfenyl-N-(cyclopentylcarbonyloxy)-1H-pyrazole carboximidamide;

109) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(cyclopentylcarbonyloxy)-1H-pyrazole carboximidamide;

110) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(tert-butylcarbonyloxy)-1H-pyrazole carboximidamide ;

111) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(isopropylcarbonyloxy)-1H-pyrazole carboximidamide;

112) 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-formylamino-4-ethylsulfinyl-N-(acetyloxy)-1H-pyrazole carboximidamide;

113) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(chloroacetyloxy)-1H-pyrazole carboximidamide;

114) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl-1-methylsulfinyl-N-(bromoacetyloxy)-1H-pyrazole carboximidamide;

115) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(1-ethylpropylcarbonyloxy)-1H-pyrazole carboximida mid;

116) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-[(3-acetyloxy)phenylcarbonyloxy]-1H-pyra sol carboximidamide;

117) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-trifluoromethylsulfonyl-1H-pyrazole-3-carboximidamide ;

118) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-trifluoromethylsulfenyl-1H-pyrazole-3-carboximidamide ;

119) 5-amino-1- [2,6-dichloro-4- (trifluoromethyl) phenyl] -N- (methoxycarbonylamino) -4-methylsulfinyl-1H-pyrazole-3-car boxaldehyde hydrazone;

120) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-(methylsulfonylamino)-4-methylsulfinyl-1H-pyrazole-3-carbox aldehyde hydrazone;

121) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-amino-4-ethylsulfinyl-1H-pyrazole-3-carboxaldehyde hydrazone;

122) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-amino-4-trifluoromethylsulfenyl-1H-pyrazole-3-carboxaldehyde hydra zone;

123) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-amino-4-methylsulfenyl-1H-pyrazole-3-carboximidamide;

124) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-(furylcarbonylamino)-4-methylsulfinyl-1H-pyrazole-3-carboximida mid; or

125)

<img file="KR20000062320A_D0004.tif" />

synthesis method

Compounds of formula I are disclosed in International Patent Publication Nos. WO 94/21606 and WO 93/06089 or International Publication No. WO 87/03781 as well as European Patent Publication No. 0295117 and Hatton et al U.S. Patent No. 5,232,940 It can be prepared according to the manufacturing method described in A person skilled in the art will select an appropriate initial reactant from the known methods above and adapt the known methods to the reactants to obtain the corresponding desired product. In the description of the methods below, it is said that the order of introduction of the various groups on the pyrazole ring is carried out in different ways and that suitable protecting groups are necessary, as will be apparent to those skilled in the art.

In the description of the methods below, when a symbol represented by a chemical formula is not specifically defined, it is "as defined above" according to the first definition of each symbol in the specification.

In a further aspect according to the invention, R₂, R₃, R₄, R₅, M, X, Y and Z are as defined above, and R₁ This amino (i.e. R₁₅ A compound of formula I, wherein a compound of formula Ia or Ib, wherein is hydrogen, can be prepared by reacting a compound of formula II with a compound of formula III:

<chemistry id="ii"><img file="KR20000062320A_D0005.tif" /></chemistry>

<chemistry id="iii">NH₂OY</chemistry>

[wherein Y is the same as defined above].

The reaction is usually carried out using an acid such as a hydrochloride salt of compound III in the presence of a base such as pyridine or an alkali metal carbonate (such as sodium carbonate) or an alkali metal acetate (such as sodium acetate) or ammonium acetate in a solvent such as methanol and / or in water at a temperature of 0 ° C to 100 ° C.

In a further aspect of the invention, R₂, R₃, R₄, R₅, M, X, Y and Z are the same as defined above d and R₁ A compound of formula (I), wherein this amino is a compound of formula (IV)

<chemistry id="iv"><img file="KR20000062320A_D0006.tif" /></chemistry>

[wherein R is alkyl].

The reaction is usually carried out using an acid salt such as a hydrochloride salt of compound III and optionally in the presence of a base such as pyridine or an alkali metal carbonate (such as sodium carbonate) or an alkali metal acetate (such as sodium acetate) or ammonium acetate in a solvent such as methanol and/or in water at a temperature of 0° C. to 100° C.

In a further aspect of the invention, R₂, R₃, R₄, R₅, M, X, Y and Z are as defined above, and R₁ A compound of formula I, wherein R is alkylamino or dialkylamino,₁ It can be prepared by reacting a corresponding compound of formula (I) wherein this amino is preferably an alkylating agent of formula R-hal, wherein R is alkyl and hal is chloro, bromo or iodo. The reaction is usually carried out in the presence of a strong base such as potassium t-butoxide or sodium hydride in a solvent such as tetrahydrofuran at a temperature of 0° C. to 100° C.

In a further aspect of the invention, R₂, R₃, R₄, R₅, M, X, Y and Z are as defined above, and R₁ A compound of formula (I), wherein hydrogen or alkyl It can be prepared by reacting a compound of

<chemistry id="v"><img file="KR20000062320A_D0007.tif" /></chemistry>

[In the formula, R₁ is hydrogen or alkyl].

In a further aspect of the invention, R₂, R₃, R₄, R₅, M, X and Z are as defined above, and R₁ is hydrogen or alkyl, and Y is hydrogen, formyl, aryl, pyridinyl and pyrimidinyl, except for (for chemical reasons only) the compounds of the formula I have the same definitions as above, except that It can be prepared by reacting a corresponding compound of formula I (wherein Y is hydrogen) with a suitable alkylating or acylating agent or Michael acceptor in the presence of a base such as triethylamine in ethane at a temperature from 0° C. to 100° C. have.

In a further aspect of the invention, Z is R₁₂NH- or R₁₃R₁₄N- (wherein, R₁₂, R₁₃ and/or R₁₄ is one or more R₁₈ is -C(O)alkyl optionally substituted with can be prepared by acylating the corresponding compound wherein Z is amino, according to one or more of the methods described above.

Cyclic amino compounds of formula I (i.e. R₁₃ and R₁₄ Z is R₁₂NH- or R₁₃R₁₄N- (wherein, R₁₂, R₁₃ and R₁₄ is alkyl or one or more R₁₈ For the synthesis of 5-alkylamino and dialkylamino compounds representing optionally substituted C-3 to C-6 alkenyl), three basic methods are suitable. A first method comprises the direct alkylation of an alkylating agent with a precursor compound of formula I, wherein Z represents amino. The second process involves the formation of an imino ether followed by a two-step sequence of reduction. A third preparation method is conjugated addition, for example, Michael-type addition.

Z is R₁₂NH- or R₁₃R₁₄N- (wherein, R₁₂, R₁₃ and/or R₁₄ is R₇S(O)_r (wherein, R₇ and r is as defined above), formyl, alkynyl, alkoxycarbonyl, alkylthiocarbonyl or aroyl) and WO 87/03781, European Patent Publication No. 0296117 and Harton U.S. Patent No. 5,232,940.

Z is hydrogen, halogen, -S(O)_nR₈, -C(O)R₇, -C(O)OR₉, alkyl, haloalkyl, -N=C(R₁₀)(R₁₁), alkylthiocarbonyl and amino, R₁₂NH- or R₁₃R₁₄Compounds of the formula I, which represent N-, have been prepared in one or more international publications WO 94/21606, WO 93/06089 and WO 87/03781, European Patent Publications EP 0295117, EP 511845, EP 403309 and EP 403300, and Harton US Patent 5,232, 940, and German Patent Publication DE 19511269.

In a further aspect of the invention, Z is OR₉ Compounds of formula I, representing

According to a further aspect of the invention, compounds of the formula I wherein the substituent Z is hydrazino, 1H-pyrrol-1-yl or 1H-pyrazol-1-yl can be prepared according to the process described in EP 0352944. The synthesis of the highly oxidation state of a compound of formula I, ie of a compound in which m is 1 or 2, can be achieved by oxidation of that compound in which m is 0 or 1.

Intermediates of formula II can be prepared by known methods (see, for example, the references listed above).

Any compound of formula II is novel and as such constitutes an additional aspect of the present invention.

Intermediates of formula IV, in which R represents alkyl, can be prepared by reaction of a compound of formula II with an alcohol of formula ROH, wherein R is alkyl. Alcohols are usually used as solvents in excess, but co-solvents such as tetrahydrofuran may be present. The reaction is usually carried out at a temperature from 0° C. to 100° C. in the presence of a base such as sodium alkoxide.

R₁ Intermediates of the formula V, which represent hydrogen or alkyl, can be prepared by the known methods described, for example, in WO 8703781 and EP 295117. For example, in an inert solvent such as tetrahydrofuran, R₁ When the reaction of the compound of formula (II) with diisobutylaluminum hydride represents hydrogen, and R₁ This compound of formula II and the formula R₁This is the case where Q (wherein Q represents, for example, Mg-Cl or lithium) represents an alkyl by reaction of an organometallic reagent.

The compounds of formula IV are novel and constitute an additional aspect of the invention.

Any compound of formula V is novel and as such constitutes an additional aspect of the invention.

Intermediates of formula III are known and can be prepared by known methods.

In a further aspect of the invention, R₁₉ A compound of formula I bis wherein is amino can be prepared by reaction of a compound of formula II bis with a compound of formula III bis:

<chemistry id="ii비스"><img file="KR20000062320A_D0008.tif" /></chemistry>

<chemistry id="iii비스">H₂NNR₂₆Y₁</chemistry>

[wherein Y and A are defined above].

The reaction is usually carried out using an acid such as a hydrochloride salt of a compound of formula III bis and a solvent in the presence of a base such as pyridine or an alkali metal carbonate (such as sodium carbonate) or an alkali metal acetate (such as sodium acetate) or ammonium acetate For example, in methanol and/or water at a temperature of 0° C. to 100° C.

In a further aspect of the invention, R₁₉ A compound of formula I bis wherein is amino can be prepared by reaction of a compound of formula IV bis with a compound of formula III bis:

<chemistry id="iv비스"><img file="KR20000062320A_D0009.tif" /></chemistry>

[wherein R represents alkyl].

The reaction is usually carried out using an acid salt, for example a hydrochloride salt, of a compound of formula III bis, optionally with a base (for example pyridine or an alkali metal carbonate such as sodium carbonate) or an alkali metal acetate (such as sodium acetate or ammonium acetate) in the presence of solvents such as methanol and/or water, usually at temperatures from 0° C. to 100° C.

In a further aspect of the invention, R₁₉ nr₃₄R₃₅ represents R₃₄ and R₃₅ A compound of formula I bis wherein one or both are substituted or unsubstituted alkyl, R₁₉ It can be prepared by reaction of a corresponding compound of formula I, in which is amino, with an alkylating agent of formula R-hal, wherein R represents alkyl and hal is chloro, bromo or iodo, preferably iodo. The reaction is usually carried out in the presence of a strong base such as potassium t-butoxide or sodium hydride in a solvent such as tetrahydrofuran at a temperature from 0° C. to 100° C.

In a further aspect of the invention, R₁₉ Using a compound of formula I bis of the above definitions, wherein bis represents hydrogen or alkyl, in the reaction of a compound of the formula V bis with a compound of the formula III bis as defined above, in the reaction of a compound of the formula II bis with a compound of the formula III bis It can be prepared using the same conditions as:

<chemistry id="v비스"><img file="KR20000062320A_D0010.tif" /></chemistry>

[In the formula, R₁₉ represents hydrogen or alkyl].

In a further aspect of the invention, Y is -S(O)_a'R₂₈, -P(O)R₂₉R₃₁, -P(S)R₂₉R₃₀, -Si(R₃₁)(R₃₂)(R₃₃), -C(O)R₂₇, -C(S)R₂₇, Y a compound of formula I bis which is cyano or nitro₁ The reaction of a compound of formula I bis, wherein hydrogen It can be prepared at a temperature of -100 to 100° C. in a common solvent in the presence of an amine or sodium carbonate.

In a further aspect of the invention, R₂₁ this R₄₃NH- or R₄₃R₄₄N- (wherein, R₄₃ and R₄₄ represents substituted or unsubstituted alkyl or substituted or unsubstituted C-3 or C-6 alkenyl) Three basic methods are suitable for the synthesis of 5-alkylamino and dialkalamino compounds of the formula I bis. The first method is R₂₁ direct alkylation of the alkylating agent with the precursor compound of formula I bis, which represents this amino. The second process involves the formation of an imino ether followed by a two-step sequence of reduction. A third preparation method is conjugated addition, for example, Michael-type addition.

R₂, R₃, R₄, R₅, R₆ and compounds of formula II bis, wherein M is a substituent as defined above, may be prepared by one or more of the following methods or methods known in the prior art: WO 94/21606, WO 93/06089, WO 87/03781, WO 97/22593 ; European Patent Publications EP 0295117, EP 0511845, EP 0403309, EP 0403300, EP 352944, EP 780378; US Patents 5,232,940, 5,047,550, 4,918,085; German Patent Publication No. 19511269.

The synthesis of compounds of formula (I bis) in higher oxidation states, i.e. compounds in which a, b, c, d, e or f is 1 or 2, can be obtained by oxidizing the corresponding compound in which said variable is 0 or 1. have.

Intermediates of formula (II bis) can be prepared according to known methods (see Examples in the above reference).

Representative compounds of the present invention

The compounds of Table 1 below are R₃ and R₅Illustrative of some of the preferred compounds of formula (I), wherein is hydrogen, they can be prepared according to the synthetic methods described herein with appropriate selection of reactants, conditions and methods generally known and clear to those skilled in the art. In Table 1, Me means methyl, Et means ethyl, where subscripts are omitted, for example, CH2 is CH₂should exist with

<tables id="1a"><img file="KR20000062320A_D0011.tif" /></tables>

<tables id="1b"><img file="KR20000062320A_D0012.tif" /></tables>

<tables id="1c"><img file="KR20000062320A_D0013.tif" /></tables>

Description of preferred embodiments

Detailed Examples of Compound Synthesis

Examples 1 to 17 and Reference Examples 1 to 24 below show detailed synthetic methods and physical properties of representative pesticidal compounds of formula (I) (and chemical intermediates thereof) according to the present invention. Table 2 shows the example compounds and others similarly prepared according to the methods described herein or other methods or detailed methods. In addition, each compound was subjected to one or more spectroscopic analyzes (IR, H¹ or F¹⁹ NMR, MS, etc.). In the table below, Me means methyl, Et means ethyl, 2-Tolyl represents 2-methylphenyl, C₂H stands for ethynyl.

Example 1

5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde (2.74 g), hydroxylamine hydrochloro A mixture of lead (0.99 g) and pyridine (1.68 g) was stirred in methanol at 46 °C for 2.8 h, evaporated and washed with water, then crystallized in ethanol as a white solid 5-amino-1-[2,6- Dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde oxime (1.74 g) is obtained (m.p. 219-221° C., decomposition). Compound 1.

In a manner similar to the above, the compounds shown in Table 2 were prepared.

<tables id="2"><img file="KR20000062320A_D0014.tif" /></tables>

Example 2

5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-trifluoromethylthio-1H-pyrazole-3-carboxaldehyde (0.66 g), methoxyamine A mixture of hydrochloride (0.2 g) and pyridine is stirred at room temperature for 26 hours. The pyridine was evaporated and the residue was dissolved in ethyl acetate/acetonitrile, washed with 1% HCl aqueous solution and dried (MgSO₄) evaporate. The residue was purified by column chromatography on silica gel eluting with hexane/ethyl acetate and 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-trifluoromethyl as a white solid. Thio-1H-pyrazole-3-carboxaldehyde O-methyloxime (0.3 g) is obtained (m.p. 129-131.5° C.). compound 9.

Example 3

5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde oxime in tetrahydrofuran (1.0 g) and Acetylchloride (0.27 ml) is added to a solution of triethylamine (0.56 ml), and the mixture is stirred for one hour. The solvent was evaporated and the residue was purified by silica gel chromatography eluting with 3:1 dichloromethane/ethyl acetate as an orange solid 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl ]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde O-(acetyl)oxime (0.83 g) is obtained (melting point 130-134° C.). compound 10.

In a manner similar to the above, the compounds shown in Table 3 were prepared.

<tables id="3"><img file="KR20000062320A_D0015.tif" /></tables>

Example 4

5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde oxime (1.38 g) in methanol/acetic acid, A mixture of 30% hydrogen peroxide (1.38 ml) sodium tungstate dihydrate (0.17 g) was stirred at 20 °C overnight, stirred at 50 °C for 4 hours, and then stirred at 20 °C overnight again. Water was added and the solid was filtered, washed with water and dried to 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfonyl-1H-pyrazole -3-carboxaldehyde oxime (0.93 g) is obtained (melting point 209.5-211° C., decomposition). compound 16.

Example 5

A solution of 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)-phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehydeoxime (0.15 g) in ethanol was added to a solution of sodium ethoxide (0.025 g) in ethanol at 20 °C, followed by the addition of iodomethane (0.023 ml). The reaction is then monitored by HPLC for 24 hours and an additional 3 equivalents of iodomethane is added. The reaction mixture is then concentrated and partitioned between dichloromethane and water. The organic layer was washed with water and dried (MgSO₄) to concentrate. Then, it was combined with the crude product of the same preparation, and purified by silica gel column chromatography eluting with hexane/ethyl acetate to obtain 5-amino-1-[2,6-dichloro-4-(trifluoromethyl) as a yellow solid. )phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde O-(methyl)oxime (0.06 g) is obtained (melting point 80° C.). compound 17.

Example 6

5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde oxime (1.5 g), methyl isocyanate (0.705) g) and dibutyl tin diacetate (2 drops) is stirred in dichloromethane in a sealed vessel at 20° C. for 2 days. The mixture was partitioned between water and dichloromethane, the organic layer was dried (Na₂SO₄), the residue was recrystallized from ethyl acetate/hexane to 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole- 3-carboxaldehyde O-(N-methylcarbamoyl)oxime (1.22 g) is obtained (m.p. 146-147° C.). compound 18.

Example 7

5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde (5.15 g) and carboxymethoxylamine hemi A mixture of hydrochloride (5.83 g) is stirred at 20° C. in pyridine/methanol for 17 h. Methanol was evaporated, the residue was washed with water and subjected to silica gel flash column chromatography eluting with acetic acid/ethyl acetate (1:9) to 5-amino-1-[2,6-dichloro-4-(trifluoro Romethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde O-(carboxymethyl)oxime (1.44 g) is obtained. As a result of mass spectrometry, the molecular weight of the product was 458. compound 19.

Example 8

To 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde oxime in tetrahydrofuran (2.0 g) Add tert-butyl nitrile (1.25 g) and stir for 4.5 h. After evaporation, the resulting orange solid was triturated with carbon tetrachloride to 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde oxime (0.24 g) (melting point 239-240° C.). compound 20.

Example 9

A solution of tert-butyldimethylsilyl chloride (0.8 g) in N,N-dimethylformamide (DMF) was mixed with 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl in DMF ]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde is added to a stirred solution of oxime (2.0 g), followed by dropwise addition of a solution of imidazole (0.72 g) in DMF over 7 minutes. The mixture is heated at 50° C. for 3.5 hours and held at 20° C. for 18 hours. The mixture was diluted (water), extracted (methyl tert-butylether) and the organic phase was transferred to NaHCO₃ solution, 5% HCl solution and NaHCO₃ After washing with solution and drying (MgSO₄), filtered and evaporated. The residue was purified by silica gel flash chromatography, 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole- as a pale yellow solid 3-carboxaldehyde O-(tert-butyldimethylsilyl)oxime (0.76 g) is obtained (m.p. 150-154° C.). compound 21.

Example 10

Stirring of 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-formyl-4-trifluoromethylthio-1H-pyrazole-3-carbonitrile (3.0 g) in ethanol To the solution, hydroxylamine hydrochloride (0.46 g) and sodium carbonate (0.9 g) aqueous solution are added. After 1 h, the mixture is poured into water, extracted (ethyl ether), dried (sodium sulfate) and evaporated. Purification by silica gel column chromatography 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-formyl-N-hydroxy-4-trifluoromethylthio-1H-pyrazole- 3-carboximidamide (0.255 g) is obtained (m.p. 72-75° C.). compound 22.

The compounds of Table 4 below were prepared in a similar manner.

<tables id="4"><img file="KR20000062320A_D0016.tif" /></tables>

Example 11

1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-formyl-4-trifluoromethylthio-1H-pyrazole-3-carbonitrile in ethanol (1.0 g), hydro A mixture of hydroxylamine hydrochloride (0.48 g) and sodium acetate trihydrate (0.94 g) is heated at reflux for 1 hour. After cooling to 20 °C, the mixture is concentrated and partitioned between water and ether. The organic phase was washed (brine), dried (magnesium sulfate) and evaporated to 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-5-hydroxyiminomethyl-4- Trifluoromethylthio-1H-pyrazole-3-carboximidamide (0.5 g) is obtained (melting point 68-72° C.). compound 23.

Example 12

A suspension of sodium ethoxide (0.34 g) in ethanol was mixed with 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole- in ethanol Add to a stirred solution of 3-carboxaldehyde oxime (2.0 g). To the mixture is added 2-iodopropane (1 ml), stirred at 20° C. overnight and evaporated. The residue (in dichloromethane) was washed with water, dried (magnesium sulfate), concentrated and purified by silica gel chromatography to 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl] -4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde O-(isopropyl)oxime (0.35 g) is obtained (melting point 128-130° C.). compound 24.

The following compounds were prepared in a similar manner:

5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1-H-pyrazole-3-carboxaldehyde O-(ethoxycarbonylmethyl ) oxime, compound 25, (melting point 127-128° C.); and

5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1-H-pyrazole-3-carboxaldehyde O-(carbamoylmethyl) Oxime, compound 26, mp 165-167 °C.

Example 13

Using a method similar to Example 12, 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole by reacting an ethanol solution of oxime with sodium ethoxide and ethyl vinylsulfone -3-Carboxaldehyde O-[2-(ethylsulfonyl)ethyl]oxime is obtained (m.p. 144-148° C.). compound 27.

Example 14

Using a method similar to Example 12, 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3- by reaction of oxime with sodium ethoxide and acrylonitrile Carboxaldehyde O-(2-cyanoethyl)oxime is prepared. Compound 28 as 85% by weight component of a mixture containing 8% oxime starting material. The mass spectroscopic analysis of the product is as follows: MS m/e = 453 (M⁺).

Example 15

Solution of 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-methyl-4-methylthio-1H-pyrazole-3-carboxaldehyde oxime (0.8 g) in trifluoro acetic acid , 30% hydrogen peroxide solution (0.32 ml) at 20 °C is added. The reaction solution was partitioned between water and dichloromethane, the organic layer was dried (magnesium sulfate), evaporated, and purified by silica gel flash chromatography eluted with dichloromethane/ethyl acetate (3:1) to 1-[2,6- Dichloro-4-(trifluoromethyl)phenyl]-5-methyl-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde oxime (0.29 g) is obtained (m.p. 210-214° C.). Compound 30 and 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-methyl-4-methylsulfonyl-1H-pyrazole-3-carboxaldehyde oxime (0.2 g, mp 211) -212 ° C). compound 31.

Example 16

5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboximidic acid methyl ester in anhydrous methanol (1.0 g) Anhydrous methoxylamine hydrochloride (0.2 g) is added to a stirred solution of After 4 h at 20 °C, the mixture is evaporated and dichloromethane and water are added. The organic layer was dried (MgSO₄), followed by chromatography on a Florisil column eluted with 3:1 dichloromethane/ethyl acetate to 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-methyl Toxyl-4-methylsulfinyl-1H-pyrazole-3-carboximidamide (0.28 g) is obtained (melting point 140-145° C.). Compound 49. Using a similar method, the following compound was prepared: 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-methoxy-4-trifluoromethylsulfi nyl-1H-pyrazole-3-carboximidamide (m.p. 169-170° C.). compound 41.; and 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-trifluoromethylsulfinyl-1H-pyrazole-3-carboximidamide (melting point 222-224 ° C). compound 40.

Example 17

5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-methoxy-4-methylsulfinyl-1H-pyrazole-3-carboximidamide in anhydrous THF ( 0.5 g) is stirred at 0-5 °C, potassium tert-butoxide (0.13 g) and iodomethane (0.081 ml) are added. After three hours, potassium tert-butoxide (0.068 g) and iodine methane (0.08 ml) are further added at 0-5 °C. The mixture was stirred at this temperature for 16 h, evaporated, and the residue purified by silica gel chromatography eluting with 3:1 dichloromethane/ethyl acetate to 5-amino-1-[2,6-dichloro-4-( Trifluoromethyl)phenyl]-N-methoxy-N'-methyl-4-methylsulfinyl-1H-pyrazole-3-carboximidamide (0.13 g) is obtained (m.p. 139-142° C.). compound 50.

Example 18

5-Amino-3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole (550 g) in pure ethanol (1.55 L) , a mixture of anhydrous hydrazine (700 g) is stirred at room temperature for 4 hours. Water (6.5 L) is added and the precipitate is filtered and washed with water. After 12 hours, the remaining precipitate is filtered off. Collect all solids to give 568 g of compound 69 as a white solid (m.p. 210° C.).

In a similar manner, the following compounds are prepared:

compound 73 melting point 170°C;

compound 74 melting point 193°C.

Example 19

A mixture of compound 69 (1.0 g) and acetic anhydride (327 mg) in p-dioxane (10 ml) is stirred at room temperature for 2 days. The mixture is evaporated, the residue is washed with hexane containing a small amount of ethyl acetate, and the suspension is filtered to give 1.08 g of compound 75 (melting point 230° C.).

Compound 85 was synthesized in a similar manner.

Example 20

A mixture of compound 69 (0.2 g) and propionic anhydride (0.07 ml) in tetrahydrofuran (5 ml) is stirred at room temperature for 6 days. The mixture is evaporated, and the residue is purified by silica gel chromatography to give 70 mg of compound 79 (m.p. 155-162° C.).

The following compounds were prepared in a similar manner.

<img file="KR20000062320A_D0017.tif" />

Example 21

A mixture of compound 69 (0.2 g) and di-t-amyldicarbonate (0.13 ml) in tetrahydrofuran (4.5 ml) is stirred at room temperature for 5 days. The mixture was evaporated, and the residue was purified by silica gel chromatography to give 20 mg of compound 89 (0.038 mmol) (m.p. 95-98 °C).

The following compounds were synthesized in a similar manner using the appropriate dicarbonate: compound 88 (m.p. 135° C.), compound 90 (m.p. 155° C.), compound 72 (m.p. 196° C.).

Example 22

To a suspension of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methylsulfinylpyrazole (20 g) in methanol (120 ml), hydroxylamine Hydrochloride (3.99 g) is added followed by triethylamine (8.0 ml). The mixture is stirred at room temperature overnight and evaporated. The residue is partitioned between water and ethyl acetate. The organic layer is washed with water, then brine. The organic layer is dried over anhydrous sodium sulfate. The solution is concentrated by evaporation of the solvent. The formed precipitate is collected by filtration. The solid was washed with a small amount of ethyl acetate to give compound 44 (16.1 g) (melting point 225-226 °C).

Reference Example 1

To 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-3-carbonitrile (50 g) in anhydrous THF - 1 M in toluene at 20 °C Diisobutylaluminum hydride (391 ml) is added dropwise over 1.5 hours. The partially evaporated mixture is quenched by addition of acetonitrile/water at 0-5 °C. The aluminum salt is filtered off, the filtrate is evaporated and the residue is extracted with dichloromethane. The extract was dried (MgSO₄), evaporation to give 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde (47.1 g) do.

In a similar manner, the following compounds shown in Table 5 were prepared.

<tables id="5"><img file="KR20000062320A_D0018.tif" /></tables>

(a) 25.0 cm x 4.6 mm SUPELCOSIL LC-18 column. Eluent MeCN/H₂O (3:1, 1 ml/min).

(b) used without purification in the next step.

Reference Example 2

A 1.4 M solution of methyllithium (31 ml) in ethyl ester was dried at -65 °C for 15 min 5-bromo-1-[2,6-dichloro-4-(trifluoromethyl) in tetrahydrofuran (THF) Phenyl]-4-methylthio-1H-pyrazole-3-carbonitrile (17.67 g) is added to a stirred solution and warmed to 0° C. for 3 hours. After cooling to -65 °C, methyl iodide (3.06 ml) in THF is added for 3 min, the mixture is warmed to -20 °C for 1.5 h, then partitioned between aqueous ammonium chloride and dichloromethane. The organic layer was dried (magnesium sulfate), evaporated and purified by HPLC flash chromatography on silica gel eluting with hexane/methyl tert-butylether, 1-[2,6-dichloro by HPLC with a purity of 90.7 area %. -4-(trifluoromethyl)phenyl]-5-methyl-4-methylthio-1H-pyrazole-3-carbonitrile (6.2 g) is obtained.

In a similar manner, the following compounds are prepared:

1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-ethylthio-5-methyl-1H-pyrazole-3-carbonitrile mp 79 - 82 °C.

Reference Example 3

30 % hydrogen peroxide (1.82 ml) at 0-5° C. in i-PrOH/H as described in [Drabowicz, et al] (supra)₂SO₄ 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-methyl-4-methylthio-1H-pyrazole-3-carbonitrile in methanol containing catalyst (5.31 ml) ( 6.2 g) of the stirred solution. The mixture is warmed to 20° C. for 17 hours. Additional hydrogen peroxide (5.46 ml) is then added in 3 portions along with the catalyst (5 ml) over the next 24 hours. After stirring for an additional 60 hours, water was added to 91.7 % HPLC area purity, CH₃CN/H₂1-[2,6-dichloro-4-(trifluoro Obtained methyl)phenyl]-5-methyl-4-methylsulfinyl-1H-pyrazole-3-carbonitrile (6.72 g).

In a similar way, the following compounds are also obtained:

1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfinyl-5-methyl-1H-pyrazole-3-carbonitrile, mp 109 - 115 °C;

5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[2-(fluoroethyl)sulfinyl]-1H-pyrazole-3-carbonitrile. mp182 - 183 °C;

from 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[2-(methylthio)ethylamino]-4-ethylsulfinyl-1H-pyrazole-3-carbonitrile 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[2-(methylsulfinyl)ethylamino]-4-ethylsulfinyl-1H-pyrazole-3-carbonitrile. mp106 - 108 ° C;

from 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[2-(methylthio)ethylamino]-4-methylsulfinyl-1H-pyrazole-3-carbonitrile 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[2-(methylsulfinyl)ethylamino]-4-methylsulfinyl-1H-pyrazole-3-carbonitrile; mp 114 - 116 ° C;

1 from 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[2-(ethylthio)ethylamino]-4-tylsulfinyl-1H-pyrazole-3-carbonitrile -[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[2-(ethylsulfinyl)ethylamino]-4-ethylsulfinyl-1H-pyrazole-3-carbonitrile, mp 138 - 140 ° C;

5-Amino-1-[3-chloro-5-(trifluoromethyl)pyrid-2-yl]-4-ethylsulfinyl-1H-pyrazole-3-carbonitrile. mp 150 - 152 ° C; and

5-Amino-1-[2,6-dibromo-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carbonitrile. mp 165 - 166 °C.

Reference Example 4

90 % Tert-Butyl nitrite (27.9 ml) in bromoform (600 ml) at 0-5° C. amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-ethylthio -1H-Pyrazole-3-carbonitrile (49.8 g) is added to a stirred solution. The mixture was stirred while warming to 20° C. for 3 hours, evaporated, and re-evaporated after addition of hexane/ethyl acetate (1:1), to 93.3 area % HPLC area purity, and CH₃CN/H₂5-bromo-1-[2,6-dichloro-4- ( Trifluoromethyl)phenyl]-4-ethylthio-1H-pyrazole-3-carbonitrile (32.65 g) is obtained.

In a similar manner, the following compounds are prepared:

5-Bromo-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylthio-1H-pyrazole-3-carbonitrile, mp 134 - 140° C.

Reference Example 5

1-(2,6-dichloro-4-trifluoromethylphenyl)-5-(E-2-methoxycarbonylethenyl)-4-trifluoromethyl in dichloromethane at -78 °C for 3 h with ozone Bubbling through the solution of thio-1H-tripyrazole-3-carbonitrile (36.6 g). After decolorizing the dark blue solution with oxygen gas, it is treated with dimethyl sulfide (19 ml) and warmed to 20° C. for 14 hours. The mixture was then washed with water, dried (magnesium sulfate), filtered and evaporated to form 1-(2,6-dichloro-4-trifluoromethylphenyl)-5-formyl-4- as white crystals (30.7 g). Trifluoromethylthio-1H-pyrazole-3-carbonitrile, mp 90° C. is obtained.

Reference Example 6

1,8-Diazabicyclo-[5,4,0]-undec-7-ene (13 ml) in toluene with 5-(2-bromo-2-carbomethoxy)ethyl-1-( It is added to a solution of 2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthio-1H-pyrazole-3-carbonitrile (45 g) and stirred for 0.5 hour. The mixture is diluted (ethyl acetate) and washed with water, hydrochloric acid solution, saturated sodium hydrogen carbonate solution and brine. The organic layer was dried (magnesium sulfate), concentrated and titrated with cold pentane to give 1-(2,6-dichloro-4-trifluoromethylphenyl)-5-(E-2-methyl) as a white solid (36.6 g). Obtained oxycarbonylethenyl)-4-trifluoromethylthio-1H-pyrazole-3-carbonitrile, mp 90°C.

Reference Example 7

A solution of 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthio-1H-pyrazole-3-carbonitrile (100 g) in acetonitrile was dissolved in acetonitrile To a mixture of heavy methyl acrylate (430 ml), copper (II) bromide (80 g) and 90% tert-butylnitrite (51 ml) is added dropwise at 0° C., warmed to 20° C., and stirred for 12 hours. . The mixture is diluted (ether), washed (water), dried (magnesium sulfate) and concentrated. Titration with hexanes gave a white solid (72.7 g) of 5-(2'-bromo-2'-carbomethoxy)ethyl-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-tri Fluoromethylthio-1H-pyrazole-3-carbonitrile, mp 122° C. is obtained.

Reference Example 8

5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinylethylsulfinyl-lH-pyrazole-3-carbonitrile in anhydrous methanol (5.0 g ), a 25% w/w sodium methoxide solution in methanol (8.95 ml) is added at 20°C. The mixture is stirred for 16 h, cooled to 0° C. and diluted with ice-cold anhydrous methanol. Carbon dioxide is passed through the solution for 15 minutes until pH 8 is reached. The precipitate was filtered off, washed (ethyl acetate) and evaporated, 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole- 3-Carboximidic acid methyl ester (3.65 g) is obtained. ¹H NMR (CDCl₃) ppm: 8.34(s,1H), 7.79(s,2H), 5.1l(brs,2H), 3.93(s,3H), 2.94(s,3H).

In a similar manner, the following compounds are prepared:

5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-trifluoromethylsulfinyl-1H-pyrazole-3-carboximidic acid methyl ester, mp 179 - 180 ° C.

Reference Example 9

To a stirred solution of 4.4'-dithiobis[5-amino-3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazole (1.0 g) in methanol, Sodium borohydride (0.03 g) is added. After 7 min, 1-bromo-2-fluoroethane (0.05 ml) is added. 5 more portions of sodium borohydride (0.15 g), also 1-bromo-2-fluoroethane (0.25 ml) are added for 5 hours. The mixture is evaporated, dichloromethane and water are added, the organic layer is dried (MgSO₄), re-evaporated to 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[2-(fluoroethyl)thio]-1H-pyrazole-3 -carbonitrile (1.09 g). mp 130 - 131.5 °C is obtained.

In a similar manner, the following compounds are prepared:

5-Amino-1-[2,6-dichloro-4-(trifluoromethoxy)phenyl]-4-ethylthio-1H-pyrazole-3-carbonitrile. mp 127 - 128 ° C.

4,4'-dithiobis[5-amino-3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H described in French Patent Applications Nos. 8816710 and 8913371 -in a similar manner to pyrazole, 4,4'-dithiobis[5-amino-3-cyano-1-[2,6-dichloro-4-(trifluoromethoxy)phenyl]-1H- used above Pyrazole can be prepared.

Reference Example 10

In a similar manner to Example 15, 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[2-(fluoroethyl)thio]-1H-pyrazole- 3-carbonitrile was oxidized with hydrogen peroxide in trifluoroacetic acid solution to 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[2-(fluoroethyl) sulfonyl]-1H-pyrazole-3-carbonitrile, mp192 - 193°C is obtained.

In a similar manner, the following compounds are prepared:

5-amino-1-[2-bromo-6-chloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carbonitrile, mp 150 - 151° C.;

5-amino-1-[2,6-dichloro-4-(trifluoromethoxy)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carbonitrile, mp 137 - 138° C.;

5-amino-1-[2-chloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carbonitrile, mp 146 - 147° C.

Reference Example 11

1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-5-amino-1H-pyrazole-3-carbonitrile in toluene (5.0 g), trimethyl orthoacetate ( 100 ml) and p-toluenesulfonic acid (0.2 g) was heated to 145° C. for 2 hours, followed by methanol distillation at 130° C. The mixture was evaporated and the residue was purified by column chromatography using 20 % ethyl acetate in hexanes, 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-5 -[1-(methoxyethylene)amino]-1H-pyrazole-3-carbonitrile (3.31 g) mp 164 - 165 °C is obtained.

Reference Example 12

1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-5-[1-(methoxyethylene)amino]-1H-pyrazole-3-carbonitrile in methanol To the suspension of (6.0 g), sodium borohydride (0.79 g) is added in 3 portions at 20° C. for 15 minutes, followed by stirring under nitrogen for 45 minutes. After evaporation, the residue was purified by column chromatography on silica gel using 15 % ethyl acetate in methylene chloride, 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl- 5-ethylamino-1H-pyrazole-3-carbonitrile (1.1 g). mp 130 - 131 °C (decomp.) is obtained.

In a similar manner, the following compounds are prepared:

1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-methylamino-4-methylsulfinyl-1H-pyrazole-3-carbonitrile, mp 147 - 150 °C (decomp.) .

In a similar manner, the following compounds are prepared using sodium cyanoborohydride instead of sodium borohydride:

1-[2-Bromo-6-chloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-5-ethylamino-1H-pyrazole-3-carbonitrile, mp 125 - 126.5 °C.

Reference Example 13

5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carbonitrile ( 4.92 g) is heated under reflux for 2 h, then stirred at 20° C. for 16 h and evaporated. Titration with boiling hexane, 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[(ethoxymethylene)amino]-4-methylsulfinyl-1H-pyrazole-3- Carbonitrile (4.05 g), mp 93 - 95 °C is obtained.

In a similar manner, the following compounds are prepared:

1-[2-Bromo-6-chloro-4-(trifluoromethyl)phenyl]-5-[1-(methoxyethylene)amino]-4-methylsulfinyl-1H-pyrazole-3-carbonone trill. This will be used directly in the next step.

Reference Example 14

To a suspension of 35% potassium hydride (0.7 g) in oil in dry N,N-dimethylformamide (DMF), 5-amino-1-[2,6-dichloro-4-(trifluoromethyl) in dry DMF Phenyl]-4-(methylsulfinyl)-1H-pyrazole-3-carbonitrile (10.0 g) is added dropwise at 4° C. for 10 minutes. After stirring for 20 minutes, vinyl ethyl sulfone (3.13 g) in dry DMF is added at 4° C. for 5 hours. The mixture is stirred under nitrogen overnight while warming to 20 °C. Ammonium chloride is added at 4° C., the mixture is extracted (ethyl acetate), washed twice with water, dried (sodium sulfonate) and evaporated. Crystallization from ethyl acetate/methanol/hexanes, 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[2-(ethylsulfonyl)ethylamino]-4-(methylsulfinyl) )-1H-pyrazole-3-carbonitrile (4.08 g), mp 131 - 132 °C is obtained.

In a similar manner, the following compounds are prepared:

1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[2-(cyanoethyl)amino]-4-(methylsulfinyl)-1H-pyrazole-3-carbonitrile , mp 55 - 57 ° C;

1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-5-[2-(phenylsulfonyl)ethylamino]-1H-pyrazole-3-carbonitrile. mp 138 - 139 ° C; and

1-[2-Chloro-4-(trifluoromethyl)phenyl]-5-[2-(ethylsulfonyl)ethylamino]-4-methylsulfinyl-lH-pyrazole-3-carbonitrile. mp 139 - 140 ° C.

Reference Example 15

To a solution of 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carbonitrile (0.5 g) in acetonitrile, Add 2-bromoacetate (0.18 g) and calcium carbonate (0.13 g) in water. The mixture is heated under reflux for 1.5 h, cooled to 25° C. and a solution of sodium hydroxide (0.05 g) in water is added. It was then heated at reflux for 1 h, evaporated and the residue purified by thin layer chromatography eluting first with 20 % methanol in dichloromethane, 1-[2,6-dichloro-4-(trifluoro Methyl)phenyl]-4-methylIsulfinyl-5-[(aminocarbonylmethyl)amino]-1H-pyrazole-3-carbonitrile (0.089 g). mp 155 - 157 °C is obtained.

Reference Example 16

To a solution of 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carbonitrile (2 g) in toluene, methyl Magnesium bromide (7 ml of a 1.4M solution in toluene/THF) is added. The mixture is stirred at 20° C. (1 h) and neutralized with saturated ammonium chloride solution. The organic layer was dried (sodium sulfate), evaporated and the residue purified by chromatography using 40 % ethyl acetate in hexanes, 3-acetyl-5-amino-l-[2,6-dichloro-4-(trifluoro Romethyl)phenyl]-4-methylsulfinyl-1H-pyrazole (0.68 g), mp 166° C. is obtained.

Reference Example 17

To a suspension of 35% potassium hydride (1.4 g) in oil in dry N,N-dimethylformamide (DMF), 1-[2,6-dichloro-4-(trifluoromethyl)phenyl in dry DMF at 4° C. A solution of ]-5-amino-4-(ethylsulfinyl)-1H-pyrazole-3-carbonitrile (5.0 g) is added and stirred for 40 minutes. 2-Chloroethyl methyl sulfide (1.39 g) is added at 4° C., and the stirred mixture is warmed to 20° C. for 40 minutes, followed by heating at 50° C. for 4 hours and at 20° C. for 3 days. Ammonium chloride solution and ethyl acetate are added, the organic layer is dried (sodium sulfate), evaporated and purified by column chromatography using 80 % methyl t-butyl ether in hexanes, 1-[2,6-dichloro-4- (trifluoromethyl)phenyl]-5-[[2-(methylthio)ethyl]amino]-4-(ethylsulfinyl)-1H-pyrazole-3-carbonitrile (0.26 g). mp 126 - 127 °C is obtained.

In a similar manner, the following compounds are prepared:

1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[2-(methylthio)ethylamino]-4-methylsulfinyl-1H-pyrazole-3-carbonitrile, mp 111 - 113 °C;

1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[-2-(ethylthio)ethylamino]-4-ethylsulfinyl-1H-pyrazole-3-carbonitrile; mp 27.5 - 29 ° C; and

1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-5-(2-propynyl)amino-1H-pyrazole-3-carbonitrile, mP140 - 141° C. .

Reference Example 18

Sulfuryl chloride (1.48 g) is added to methyl disulfide (3.16 g) in methyl t-butyl ether, and stirred for 5 hours to obtain methyl sulfenyl chloride. This was heated to reflux under nitrogen in methyl t-butyl ether for 5 min. 5-amino-1-[2-bromo-6-chloro-4-(trifluoromethyl)phenyl]-1H-pyrazole-3-carbonone To a solution of trill (4.0 g). After 1 h, the cooled mixture is washed alternately with water, sodium bicarbonate solution and water, dried (sodium sulfate) and evaporated. Purification by chromatography on silica gel eluting with hexanes/ethyl acetate (9:1), 5-amino-1-[2-bromo-6-chloro-4-(trifluoromethyl)phenyl]-4- Obtained methylthio-1H-pyrazole-3-carbonitrile (3.15 g), mp 178 - 180 °C.

In a similar manner, the following compounds are prepared:

5-Amino-1-[3-chloro-5-(trifluoromethyl)pyrid-2-yl]-4-ethylthio-1H-pyrazole-3-carbonitrile.

Reference Example 9

[Process 1]

Bromine (0.5 ml) is added to a stirred solution of sodium thiocyanate (1.7 g) in anhydrous methanol at -65°C. A solution of 5-amino-1-[2-chloro-4-(trifluoromethyl)phenyl]-1H-pyrazole-3-carbonitrile (1.5 g) in anhydrous methanol was added over 10 minutes, and the stirred mixture was stirred for 16 Warm to 20° C. for hours. After injection into water, the precipitate was collected and dried, 5-amino-1-[2-chloro-4-(trifluoromethyl)phenyl]-4-thiocyanato-1H-pyrazole-3-carbonone Trill (1.64 g) is obtained. HPLC (C-18 column, 3:1 CH₃CN/H₂10 ml/min elution with O) indicates a compound corresponding to a peak of 86.6 area % at 5.11 min.

[Process 2]

Iodomethane (0.7 ml) was mixed with 5-amino-l-[2-chloro-4-(trifluoromethyl)phenyl]-4-thiocyanato-1H-pyrazole-3-carbon in methanol at 4°C Inject into a stirred suspension of Trill (1.64 g). A 10% aqueous solution of sodium hydroxide (2.8 ml) is added, and the reaction mixture is stirred at 4° C. for 1 hour, poured into water, and extracted with dichloromethane and ethyl acetate. dry (Na₂SO₄) The combined organic layers were evaporated, purified by flash chromatography on silica gel eluting with 4:1 hexane/ethyl acetate, titrated with hexane/dichloromethane, followed by 5-amino-1-[2-chloro-4-( Trifluoromethyl)phenyl]-4-methylthio-1H-pyrazole-3-carbonitrile (0.4 g), mp 129 - 132 °C is obtained.

In a manner analogous to step 1, the following compound is obtained:

A) 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylthio-1H-pyrazole-3-carbonitrile used with iodomethane in step 2 5-amino-1-[2,6-dichloro-4-(trifluoromethoxy)phenyl]-4-thiocyanato-1H-pyrazole, such that , mp 147 - 148° C. is prepared.

B) 5-amino-1-[2,6-dibromo-4-(trifluoromethyl)phenyl]-4-methylthio-1H-pyra used together with iodomethane and methanol as solvents in step 2 Sol-3-carbonitrile. 5-amino-1-[2,6-dibromo-4-(trifluoromethyl)phenyl]-4-thiocyanato-1H-pyrazole-3- carbonitrile.

Reference Example 20

of 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazole-3-carbonitrile (9.8 g) and N-iodosuccinimide (8.87 g) The suspension was heated at reflux in carbon tetrachloride for 3.5 h, then cooled; Wash with sodium bisulfite solution, sodium hydroxide and water. The dried (magnesium sulfate) solution was evaporated and purified by chromatography on silica gel eluting with dichloromethane, 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]- 4-iodo-1H-pyrazole-3-carbonitrile (4.0 g), mp 212 - 214 °C is obtained.

Reference Example 21

5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-iodo-1H-pyrazole-3-carbonitrile (1.96 g) was mixed with dimethylformamide dimethyl acetal (10 ml) at 20 °C for 2 hours, excess ice/water is added, the solid is filtered off and oven-dried, 1-[2,6-dichloro-4-(trifluoromethyl)phenyl ]-4-iodo-5-N-(dimethylaminomethyleneamino)-1H-pyrazole-3-carbonitrile (1.53 g), mp 177 - 180°C is obtained.

Reference Example 22

The cadmium is washed with hydrochloric acid (10%), water, ethanol and ether and dried to prepare activated cadmium. Dibromodifluoromethane (317.2 g) in dry N,N-dimethylformamide (DMF) was added to a mixture of activated cadmium (212.5 g) in dry DMF at an initial 0-5 °C for 1 h, 35 °C Stir under nitrogen at less initiation. Hexamethylphosphoramide (11, dry) is added followed by copper (I) bromide (108.5 g), after 15 min 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]- 4-iodo-5-N-(dimethylaminomethyleneamino)-1H-pyrazole-3-carbonitrile (100.0 g) is added and the mixture is heated at 75° C. for 2 hours. The cooled mixture is filtered (Celite), concentrated, diluted (water) and filtered. The product was washed (hot water), 1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-N-(dimethylaminomethyleneamino)-4-trifluoromethyl-1H-pyra Obtained sol-3carbonitrile (80.9 g), mp 156 - 157.5 °C.

Reference Example 23

1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-N-(dimethylaminomethyleneamino)-4-trifluoromethyl-1H- in tetrahydrofuran and hydrochloric acid (6 N) A solution of pyrazole-3-carbonitrile (120.5 g) is heated under reflux for 24 h, concentrated and filtered. The solid was mixed with dichloromethane and filtered, 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-trifluoromethyl-1H-pyrazole-3-carbonitrile (88.2 g), mp 191 - 193 °C is obtained.

Reference Example 24

A solution of 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylthio-1H-pyrazole-3-carbonitrile (1.0 g) in tetrahydrofuran was 4 To anhydrous sodium hydride (0.13 g) stirred under nitrogen in tetrahydrofuran at &lt;RTI ID=0.0&gt; After 2 h, iodomethane (0.34 ml) is added and the mixture is stirred at 20° C. overnight and treated with ammonium chloride solution. Extraction (ethyl acetate), drying (sodium sulfate) and evaporation followed by chromatography on silica gel eluting with ethyl acetate/dichloromethane (1 : 9) to 1-[2,6-dichloro-4-(trifluoro Obtained methyl)phenyl]-5-dimethylamino-4-methylthio-1H-pyrazole-3-carbonitrile (0.5 g), mp 118 - 119 °C.

Uses as acaricides, insecticides, acaricides and nematicides

Using the compounds of the present invention, the following representative test procedures were carried out to prepare mites of the present invention; certain insects such as aphids, two species of caterpillars, flies and three species of beetle (beetle larvae) (eating 1 leaf and ingesting 2 roots); and the pesticidal use and activity of the present invention against nematodes. The specific species tested were:

Genus, species common name (abbreviation)

Tetranychus urticae three-point spider mite TSM

Aphis nasturtii buckthorn aphid BA

Spodoptera eridania Southern Army Beetle SAW

Epilachna varivestis mexican bean beetle MBB

Musca domestica housefly HF

Diabrotica u, howardi Southern corn rootworm SCRW

Diabrotica virgifera western corn rootworm WCRW

Meloidogyne incognita Southern Root-Knot Aphid SPKN

Aphis gossypii Cotton Aphid CA

Schizaphis graminum barley aphid GB

Heliothis virescens Tobacco shoot-eating caterpillar TBW

Formulation:

Test compounds were formulated for use according to the following methods used in each test procedure.

For testing mite, aphid, southern armyworm, Mexican bean beetle, and tobacco budworm, 10 mg of the test compound was mixed with 160 mg of dimethylformamide; 838 mg of acetone, 2 mg of Triton X-172: Triton X-152 (predominantly anionic and nonionic low-foaming emulsifiers, respectively, anhydrous mixtures of alkylaryl polyether alcohols and organic sulfonates), and 98.99 g of water are added to a solution or a suspension was prepared. As a result, the test compound concentration was 100 ppm.

For the housefly test, the initial formulation was prepared in a similar manner as above, except that the corresponding other ingredients were adjusted to give a concentration of 200 ppm in 16.3 mg of water. Final dilution with an equal volume of 20% by weight of an aqueous solution of sucrose gave a test compound concentration of 100 ppm. If necessary, the dispersion was completed by sonication.

For southern and western corn rootworm testing, solutions or suspensions were prepared in the same manner as used for the initial 200 ppm concentration for housefly. An aliquot of the 200 ppm formulation was used, diluted with water according to the required test concentration.

For phylogenetic testing of southern root-node nematodes and southern beetle, cotton aphid, tobacco leaf budworm and barley aphid, 15 mg of test compound was added to 250 mg of dimethylformamide, 1250 mg of acetone and 3 mg of the above-mentioned emulsifier mixture. was added to prepare a mother liquor or suspension. Water was added to give a test compound concentration of 150 ppm. If necessary, the dispersion was completed by sonication.

For the Tobacillus larvae contact test, a mother liquor was prepared at the required serial dilution concentration by dissolving the compound in acetone and then further dilution.

Test procedure:

The formulated test compound was evaluated for its pesticidal activity at its specific concentration (ppm by weight) according to the following test procedure.

Two-point spider mite: Leaves infected with the adult and nymph stages of two-point spider mite obtained from parent culture were placed on the main leaves of two bean seedlings growing in 6 cm peat pots. Sufficient numbers (150 - 200) of test mites were transferred to fresh seedlings for 24 hours. Potted seedlings (1 pot per compound) were placed on a rotating spinneret at 40 psig. Using a DeVilbiss spray gun adjusted to atmospheric pressure, 100 ml of the test compound formulation at 100 ppm was sprayed sufficient to wet the seedlings. As an untreated control, 100 ml of a water-acetone-DMF-emulsifier solution containing no test compound was also sprayed onto the infected seedlings. In the same manner, a control treated with a commercially available industrial compound, dicopol or hexythiazox was tested as a standard. After the sprayed seedlings were left for 6 days, the lethality of the self-powered ones was measured.

Two-point spider mite (insecticidal egg test): Eggs were obtained from adults of two-point spider mite obtained from parent culture. Highly infected leaves from the parent culture were placed on uninfected soybean seedlings. After allowing the female to lay eggs for about 24 hours, the leaves of the seedlings were immersed in a TEPP (tetraethyl diphosphate) solution to kill the automatons and prevent further egg laying. After the seedlings were dried, repeating the immersion procedure did not affect the fertility of the eggs. Potted seedlings (1 pot per compound) were placed on a rotating tumbler, 40 psig. Using a Devillevis spray gun adjusted to atmospheric pressure, 100 ml of 100 ppm of the test compound formulation was sprayed sufficient to wet the seedlings. As an untreated control, 100 ml of a water-acetone-DMF-emulsifier solution containing no test compound was also sprayed onto the infected seedlings. A commercially available industrial compound formulated in the same manner, typically a control treated with demethone, was tested as a standard. After the sprayed seedlings were left for 7 days, the egg lethality was investigated while recording the residual activity of the awakened larvae.

Buckwheat or Cotton Aphid: Adult or nymph stages of buckthorn or cotton aphid were grown on potted orchid or cotton seedlings, respectively. Potted seedlings infected with 100 to 150 aphids (1 pot per tested compound) were placed on a rotating rotator and 100 ml of 100 ppm of the test compound formulation was applied to the seedlings using a Devillevis spray gun adjusted to 40 psig atmospheric pressure. It was sprayed enough to get wet. As an untreated control, 100 ml of a water-acetone-DMF-emulsifier solution containing no test compound was also sprayed onto the infected seedlings. In the same manner, a control treated with a commercially available industrial compound, malathion or cyhalothrin was tested as a standard. After spraying, the pollen was left on buckthorn aphid for 1 day or cotton aphid for 3 days, then the number of dead aphids was counted.

Southern Beetle: Potted soybean seedlings were placed on a rotating rotating plate and 100 ml of 100 ppm of the test compound formulation was sprayed using a Devillevis spray gun adjusted to 40 psig atmospheric pressure. As an untreated control, 100 ml of a water-acetone-DMF-emulsifier solution containing no test compound was also sprayed onto the infected seedlings. A control treated with a commercially available Genup compound formulated in the same manner, cypermethrin or sulfophos, was tested as a standard. Upon drying, the larvae were placed in plastic cups lined with wet filter paper. Five randomly selected, 2nd instar southern beetle larvae were introduced into each sealed cup and left for 5 days. Larvae that were unable to move the length of their body even when given a stinging stimulus were considered dead.

Tobacco larvae: Potted cotton seedlings were placed on a rotating rotating plate and 100 ml of 100 ppm of the test compound formulation was sprayed using a Devillevis spray gun adjusted to 40 psig atmospheric pressure. As an untreated control, 100 ml of a water-acetone-DMF-emulsifier solution containing no test compound was also sprayed onto the infected seedlings. A control treated with a commercially available industrial compound formulated in the same way, cypermethrin or sulfophos, was tested as a standard. Upon drying, the larvae were placed in a plastic dish containing a sheet of filter paper and a wet dental wick. Then, one randomly selected 2nd instar Tobacillus larvae was introduced into each closed cup and left for 5 days. Caterpillars that could not move as much as their body length even when stimulated by stabbing were considered dead.

Mexican bean beetle: Potted bean seedlings were placed on a rotating rotating plate and 100 ml of 100 ppm of the test compound formulation was sprayed using a Devillevis spray gun adjusted to 40 psig atmospheric pressure sufficient to wet the seedlings. As an untreated control, 100 ml of a water-acetone-DMF-emulsifier solution containing no test compound was also sprayed onto the seedlings. A control treated with a commercially available industrial compound formulated in the same way, cypermethrin or sulfophos, was tested as a standard. Upon drying, the larvae were placed in plastic cups lined with wet filter paper. Then, randomly selected 5 second instar Mexican bean beetle larvae were introduced into each sealed cup and left for 5 days. Caterpillars that could not move as much as their body length even when stimulated by stabbing were considered dead.

Houseflies: Houseflies 4 to 6 days old were bred under controlled conditions according to the Chemical Specialties Manufacturing Association (Blue Book, McNair-Dorland Co., NY 1954; pp243-244, 261). Flies were fixed by anesthesia with carbon dioxide, and 25 fixed individuals, males and females, were transferred to cages with standard food filters and surfaces covered with wrapping paper. 10 ml of the test compound formulation at 100 ppm was added to the soufflé cup containing the absorbent cotton pad. As an untreated control, 10 ml of a water-acetone-DMF-emulsifier-sucrose solution containing no test compound was applied in a similar manner. A control treated with malathion, a commercially available industrial compound formulated in the same manner, was treated as a standard. Prior to introducing the anesthetized flies, a bait cup was introduced inside the food strainer. After 24 hours, flies that did not show any movement after stimulation were considered dead.

Southern or Western corn rootworm: To a jar containing 60 g of sandy clay soil, add 1.5 ml of an aqueous formulation consisting of 200 ppm test compound formulation aliquots, test compound, 3.2 ml water and 5 pre-germinated corn seedlings to a final It was diluted with water to an appropriate soil concentration. The jar was shaken thoroughly to obtain a uniform distribution of the test formulation. Then, 20 corn rootworm eggs (or, in the case of WCRW, optionally 10 first instar larvae) were placed in a hole made of soil. Then, optionally vermiculite (1 mL) and water (1.7 mL) used in the case of the WCRW test were added to this hole. In a similar manner, an untreated control was prepared by applying an equal sized aliquot of a water-acetone-DMF-emulsifier solution containing no test compound. In addition, a control treated with a commercially available industrial compound (typically terbufos, phonophos, porate, chlorpyrifos, carbofuran, isazophos, or etoprop) formulated in the same manner as a test standard was used as required. After 7 days, live rootworm larvae were counted using the known "Berlese" funnel extraction method.

Southern root-node nematode: Infected roots of tomato seedlings containing egg mass of Southern root-node nematodes were removed from the parent culture, and the soil was washed by shaking and washing with tap water. Nematode eggs were isolated from the root tissue and washed with water. A sample of the egg suspension is fed onto a micro sieve on a receptor, wherein the amount of water is adjusted to contact the sieve. From the container, the immature was collected on a micro sieve. The bottom of the conical container was filled with sanitized vermiculite, and about 200 ml of sterile soil was filled to within 1.5 cm of the top. A 150 ppm aliquot of the test compound formulation was then pipetted into a hole made in the center of the soil within the cone. The commercial industrial compound phenamiphos formulated in a similar manner was treated as standard. As an untreated control, a water-acetone-DMF-emulsifier solution containing no test compound was applied in the same manner. Immediately after the soil was treated with the test compound, 1000 second-stage young southern root-node nematodes were added to the top of each cone. After 3 days, one healthy tomato seedling was transplanted into the cone. The column containing the infected soil and tomato seedlings was left in the greenhouse for 3 weeks. At the end of the test, the roots of the tomato seedlings were removed from the cones, and compared to the untreated control, the growth was evaluated in the following grading steps.

One - Severe colonization, same as untreated control

3 - light filling

4 - very light chungyeong

5 - No filling, i.e. fully controlled

The results are then reported to the ED (effective dose for 3 or 5 filling grades).₃ or ED₅converted to a value.

Southern Beetle on Tomatoes - Phylogenetic Assessment: This test was performed in conjunction with Southern root-node nematode assessment (described below). For the evaluation of nematodes, tomato seedlings cultured in soil (with an initial compound test selection rate of 6.6 ppm soil concentration or about 15 ppm solution concentration) were used for evaluation of compound uptake through roots and continuous lineage transport to tomato leaves. At the conclusion of the nematode test, tomato leaves were excised 21 days after treatment, placed in plastic containers, and infested with second instar larvae of the southern beetle. After about 5 days, the % lethality of the larvae was measured.

Cotton Aphid and Tobacillus Aphid (Cotton Phase) and Barley Aphid and Tobacco Aphid (Sorghum Phase) - Phylogenetic Assessment: 6 cm pollen containing cotton and sorghum seedlings by applying 7.0 ml aliquots of 150 ppm of nematode test solution A 10.0 ppm soil concentration dose was delivered as a solution to the Cotton seedlings were pre-infected with cotton aphid about 2 days before treatment and with barley aphid about 1 day before treatment. After the seedlings were left for about 3 days, they were evaluated for aphid activity. On day 6 again, seedlings were evaluated for aphid activity, cotton aphid and barley aphid counted, and lethality assessed. Some cotton and sorghum leaves were excised, individually placed in plastic containers, and infested with second-instar larvae of tobacco leaf larvae. Potted seedlings were immersed in sulfotep to kill any remaining aphids and returned to the greenhouse for regrowth. 13 days after treatment, the remaining leaves were excised and fed to Tobacco leaf worms. Mortality was assessed 6 days after infection.

Cotton Aphid and Southern Beetle (Cotton Phase) and Barley Aphid and Southern Beetle (Sorghum Phase) - Phylogenetic Assessment: A mother liquor or suspension was prepared in 6 cm pots containing cotton and sorghum seedlings as a solution in soil at 20 ppm. 5 ml of the concentration dose (and serial dilutions) were delivered. Cotton seedlings were pre-infected with cotton aphid approximately 2 days prior to treatment and with barley aphid 1 day prior to treatment. After the seedlings were left for about 3 days, they were evaluated for aphid activity. On day 6 again, seedlings were evaluated for aphid activity, cotton aphid and barley aphid counted, and lethality assessed. Portions of cotton and sorghum leaves were excised, individually placed in plastic containers, and infested with second instar southern beetle larvae. Potted seedlings were immersed in sulfotep to kill any remaining aphids and returned to the greenhouse for regrowth. The remaining leaves were excised 13 days after treatment and fed to southern beetles. Mortality was assessed 6 days after infection.

Cotton Aphid and Southern Beetle (Cotton and Oat Phase) - Seed Treatment Evaluation: Industrial material was applied to oats and cotton seeds by placing the compounds and seeds in appropriately sized jars and rotating the jars on a ball mill. The amount of material applied to the seeds was by weight. The seeds were then transplanted. Once germination and shoots appeared, seedlings were infested with host insects at appropriate intervals. The lethality was evaluated on the insect.

Tobacillus Sprout - Contact Assessment: The following topical method provides an assessment of the contact toxicity of compounds to Tobacillus leafworm larvae. The test compound solution serially diluted two-fold to a concentration of 10 to 0.16 μg/μl was repeatedly applied to the back of about 20 mg of Tobacillus larvae in 1 μl increments using a micro-syringe. This corresponds to a dose of 500 to 8 μg/g body weight. A control treated with acetone without test compound was also applied. A control treated with a commercially available industrial compound, cypermethrin or thiocarb in acetone was also applied as a standard. The treated larvae were individually placed in individual plastic Petri dishes containing untreated cotton leaves and wet dental wicks. The treated larvae were maintained at about 27° C. and 50% relative humidity. % lethality was assessed at 1 and 4 days post treatment.

All of the compounds Nos. 1 to 118 of the present invention exhibited insecticidal activity in at least one of the above evaluation methods, together with particularly excellent activity in the phylogenetic test.

Method and composition

The present invention provides a method for locally controlling arthropods, particularly insects or mites inhabiting the plant growth zone. Control of such foliar pests can be provided, for example, by application by soil spray or granular application to plant roots or seeds with continuous line current in the plant growth zone, or by direct application to leaves. The lineage activity not only remains at the point of application, but can be current from a remote part of the plant, such as from a treated leaf to an untreated leaf, or from one side of a leaf to the other. Examples of the kind of pests that can be systemically controlled by the arylpyrazole of the present invention include Homoptera (stick-sucking insects), Hemiptera (sting-sucking insects), Thysanoptera. do. The present invention is particularly suitable for aphids and spores.

As is clear from the insecticidal uses described above, the present invention relates to arylpyrazoles which are pesticidally active, and to arthropods, in particular insects or mites; plant nematodes; or a method of use for the control of multiple pests, including parasitic or protozoan pests. Accordingly, the arylpyrazoles of formula (I) or their pesticidally acceptable salts are advantageously used in practical applications such as agriculture, or horticultural crops, forests, veterinary medicine or livestock farming, or public health. In this regard, whenever the term "arylpyrazoles of formula I" is used, the term includes arylpyrazoles of formula (I) and their pesticidally acceptable salts. The term "arylpyrazoles of formula I" includes the arylpyrazoles of formula (I) and their pesticidally acceptable salts.

Accordingly, the present invention relates to the control of pests comprising topical treatment (e.g. by application or application) with an effective amount of an arylpyrazole of formula (I) or a pesticidally acceptable salt thereof, wherein the substituents are as defined above. Local control methods are provided. The topic includes, for example, the pest itself or the place in which the pest inhabits or is raised (plants, animals, fields, buildings, land, forests, orchards, waterways, soil, plants or soil products, etc.).

The arylpyrazoles of the present invention are additionally used with corn rootworms, termites (particularly for protecting structures), root maggots, worm larvae, root weevil, stalkbore, nectar, root aphids or grubs and It can be used to control the same soil pests. They may also be used to provide activity against mites or plant pathogenic nematodes, such as root-nodules, cysts, daggers, damage, or stem or bulbous nematodes. For the control of soil pests such as, for example, corn rootworms, the arylpyrazoles are advantageously applied or introduced at an effective rate into the soil or seeds or growing plant roots in which the grain is to be sown or sown.

In sanitation sites, arylpyrazoles are particularly effective in pests, especially filth flies or other dwarf pests, such as houseflies, stall flies, horn flies, stag flies, horse flies, small worms, many pests such as mosquitoes, black flies or mosquitoes. useful to suppress

The arylpyrazoles of the present invention can be used in the following applications and in the following pests, including arthropods, especially pests or mites, nematodes, parasites or protozoan pests:

For example, in the protection of stored products such as grains, including grains or wheat flour, grains, peanuts, animal feed, wood, or household goods such as carpets and textiles, the arylpyrazoles of the present invention can be used in arthropods, more particularly weevil, Beetles, including moths or mites, for example, Ephesia espi. (Ephestia spp.), (wheat moth), Anthrenus espi. (Anthrenus spp.), (carpet beetle), Trivolium spp. (Tribolium spp.) (Wheatworm), Cytophilus spp. (Sitophilus spp.) (grain weevil) or Acarus spp. (Acarus spp.) Useful against attack by (mite).

In the control of domestic or industrial infested cockroach, ant or termite or similar arthropod pests or in the control of mosquito larvae in waterways, wells, reservoirs or other flowing or stationary waters.

For radical treatment, termites, for example Reticulthermes espepi. (Reticulitermes spp.), Heterothermes spp. (Heterotermes spp.), Recoptotermes spp. (Coptotermes spp.) A structure or soil that protects against attacks caused by it.

For example, Heliotis virescens, (tobacco bud worm), Heliotis armigera and Heliotis zea. Such as Heliotis espepi. (Heliothis spp.) In the structure of adults, larvae or eggs of Lepidoptera (butterflies and moths), adults and Coleoptera (beetles) such as Antonomus esphipi. (Anthonomus spp.), such as grandis (corn ball weevil), Leptinotarsa decemlineata (Colorado potato beetle), Diabrotica espepi. Against (Diabrotica spp.) (corn rootworm). Heteroptera (Hemiptera and Homoptera) such as Psila espepi. (Psylla spp.), Bemisia spp. (Bemisia spp.) Trialeurodes spp. (Trialeurodes spp.), Apis spp. (Aphis spp.), Mijus spp. . (Myzus spp.), Phyloxera spp. in Megourusa visiae. (Megoura viciae Phylloxera spp.), Nepotetics spp. (Nephotettix spp) (rice leaf hopper), nelapartettix spp. (Nilaparvata spp.) Against.

Difpera such as Musca espepi. (Musca spp.) Against. Against thysanoptera, such as Thrips tabaci. Locusta and shistoserca espipi. (Locusta and Schistocerca spp.) (Graffiti and Locusts) such as Grylus spp. (Gryllus spp.) and Acheta spp. espepi. For example, Blatta orientalis, Periplaneta americana (Periplaneta americana), Blatta germanica (Blatta germanica), Locusta migratoria migratorioides (Locusta migratoria migratorioides), and against orthoptera such as Schistocerca gregaria (Schistocerca gregaria) . Colembola such as Periplaneta espepi. (Periplaneta spp.) and Vlatella spp. (Blattela spp.) Against (cockroaches). Isoptera such as Coptothermes espepi. (Coptotermes spp.) Against (termites).

Akari (mite) such as Tetranicus espepi. (Tetranychus spp.), and Panonicus spp. (Panonychus spp.) corresponds to.

Against nematodes that directly attack plants or trees of importance in agriculture, forestry or horticulture, or which reproduce bacterial, viral, microbial or bacterial diseases of plants. For example root-knot nematodes such as meloidozin sp. (Meloidogyne spp.) (eg M. incognita)

Vertebrates, in particular warm-blooded vertebrates, for example arthropods, parasites or protozoa, which parasitize inside or outside of livestock such as cattle, sheep, goats, horses, pigs, poultry, dogs or cats, for example mites, Ticks (e.g., Suborder Aphids, Boophilus spp.) For example Boophilus microplus (microplus), Rhipicephalus spp. (Rhipicephalus spp.), e.g. Rhipicephalus afendi Culatus Ornithodorus spp. (appendiculatus Ornithodorus spp.) (eg Ornithodorus moubata) and mite (eg Damalinia spp.); Diptera) (eg Aedes spp.), Anopheles spp. Musca spp. (Musca spp.), Hippoderma spp. (Hypoderma spp.)); Hemiptera (Hemiptera.); Dictyoptera (eg Periplaneta spp., Blatella spp.); Against Hymenoptera in veterinary medicine or livestock dairy fields or maintenance of public health; Against infection of gut traces, for example by parasitic nematode worms, for example from the family Trichostrongylidae; For example, Aemeria espepi. (Eimeria spp.), for example Trypanosoms cruzi, Reysaminia spp. (Leishaminia spp.), Plamodium spp. (Plasmodium spp.), Babesis spp. (Babesis spp.), Trichomonadidae spp. (Trichomonadidae spp.), Toxoplasma spp. (Toxoplasma spp.) and Taileria spp. (Theileria spp.) in the suppression and treatment of protozoan diseases.

In practice for the suppression of nematode plagues of arthropods, particularly insects or mites, or plants, the method comprises applying, for example, an effective amount of an arylpyrazole of the present invention to the plant or medium in which they grow. In this method, the active arylpyrazole is usually applied at an effective rate ranging from about 5 g to about 1 kg of active arylpyrazole per hectare of site to be treated to a site that inhibits arthropod or nematode infection. Under ideal conditions, depending on the plague being suppressed, a lower ratio may provide sufficient protection. On the other hand, in adverse weather conditions, pest tolerance or other factors may necessitate the use of high proportions of the active ingredient. The optimal ratio usually depends on a number of factors, for example the type of pest to be suppressed, the type or growth stage of the infected plant, the heat interval or the method of application. More preferably, the effective proportion of active arylpyrazole ranges from about 50 g/hr to about 400 g/hr.

When the pest is soil-spreading, the active arylpyrazole in the commonly formulated composition is uniformly distributed (ie, sprayed or banded) over the treated area in any convenient manner and is preferably from about 5 to about 1 kg ai/ha, preferably It is preferably applied at a rate of about 50 to 250 g ai/ha. When applied as a rooting method of seedlings or drip irrigation for plants, the liquid solution or suspension contains from about 0.075 to about 1000 mg ai/l, preferably from about 25 to about 200 mg ai/l. If desired, it can be applied to the field or crop area or adjacent areas of plants or seedlings that are normally protected from attack. The active ingredient can be sprayed over the entire area with water to be washed into the soil or left to the natural action of precipitation. During or after application, if desired, the blended arylpyrazole may be mechanically distributed to the soil, for example, using plowing, disking, or brake chains. It can be applied before, during, and after sprouting, but can be applied before or after germination.

Arylpyrazoles and pest control methods thereof of the present invention can be used in field, feed, breeding, greenhouse, pasture or vineyard, ornamental, or breeding or forestry, for example, grain (such as wheat or rice), cotton, vegetable (such as pepper), crops (such as sugar beet, soybean or rapeseed oil), pasture or fodder crops (such as corn or sorghum), pasture or orchard (such as fruit kernels or citrus fruits or citrus), ornamental plants in greenhouses or in gardens or parks , of particular importance in the protection of flowers or shrubs.

It is also of value for the protection of timbers (stands, logging trees, conifers, storage trees or rescue trees), for example, from attack by leaf bees or beetles or termites.

It is used for the protection of stored products such as cereals, fruits, peanuts, spices or tobacco if the product is whole, milled or arylpyrazoles from moth, beetle, mite or grain weevil attack. It also protects stored animal products such as skin, hair, wool or hides of natural or modified form (eg carpets or textiles) from moth or beetle attack and stored meat, fish or grain from beetle, mite or flies attack.

Additionally, the arylpyrazoles of the present invention and methods of use thereof include the inhibition of arthropods, parasites or protozoa that are harmful or that transmit or act as disease agents in livestock, such as those mentioned hereinafter, and more specifically mites. , mites, lice, fleas, small insects, or irritants, are of particular importance in the suppression of sludge or myiasis flies. The arylpyrazoles of the present invention are particularly useful for the inhibition of arthropods, parasites or protozoa that are present inside domestic host animals or that feed on the skin or suck blood, and for this purpose it can be administered orally, parenterally, transdermally or topically. have.

Moreover, the arylpyrazole of the present invention may be useful for diseases caused by infection from protozoan parasites of the genus Eimeria, coccidiosis. It is a significant potential cause of economic loss in livestock and birds, especially those raised or maintained under intensive conditions. For example, cattle, sheep, pigs or rabbits may be affected, but the disease is particularly important in poultry, particularly chickens. Administration of small doses of the arylpyrazoles of the present invention, preferably by feed and in combination, is effective prophylactically or greatly reduces the incidence of coccidiosis. Arylpyrazole is effective against the cecal and visceral forms. Moreover, the arylpyrazoles of the present invention also exert a controlling effect on oocytes by greatly reducing the number and sporulation of propagated ones. Poultry diseases are spread by birds that eat harmful organisms, usually from contaminated litter, ground, and food or drink droplets. The disease is represented by bleeding, accumulation of blood in the cecum, passage of blood in the droplets, weakness, and digestive disorders. The disease often ends in the death of the animal, but chickens that survive severe infection have a substantially reduced market value as a result of the infection.

The compositions described hereinafter for use as field-grown crops or seed dressings can usually be used instead in topical use or storage products for animals, household products, properties of the general environment and protection of the area. Suitable means of use of the arylpyrazoles of the present invention include:

as foliar, dusting, granular, spraying, foaming on cultivated crops or as a soil or root treatment by liquid drench, dusting, granules, mist or foaming as a suspension of a finely divided or encapsulated composition; administration to seeds of crops for use as seed dressings by liquid slurry or dust;

To animals infected with or exposed to infection by arthropods, nematodes or protozoa, for example, a composition in which the active ingredient exhibits an instantaneous and/or delayed action over a period of time against the vaginal, nematode or protozoa is provided, for example. or suitable orally ingestible pharmaceutical formulations, edible baits, salt licks, meal aids, infusion formulations, sprays, baths, soaks, showers, jets, dusts, oils, shampoos, creams and wax smears. or oral, parenteral or topical use incorporated into livestock self-treatment systems;

As sprays, mists, dusts, smokes, wax smears, lacquers, granules or baits, or as a spray, mist, dust, smoke, or waterway in the environment of a common or specific location where the plague may harbor, including stored products, wood, household products, or domestic or industrial premises; , drip supply to wells, reservoirs or other running water;

Livestock in feed to suppress fly larvae that feed on the dung.

Indeed, the arylpyrazoles of the present invention most often form part of the composition. The composition may be used in an arthropod: specifically an insect or a mite; Nematodes: or can be used to control parasitic or protozoan pests. The composition may be in any form known in the art suitable for use in the desired plague in any premises or in an indoor or outdoor area, or by internal or external administration to vertebrates. Said composition comprises one or more arylpyrazoles of formula (I) or pesticidally acceptable salts thereof, such as those described above, suitable for the intended use and an agronomically or medically acceptable, for example solid or liquid carrier or diluent, It is contained as an active ingredient in combination or in association with one or more other compatible ingredients, such as adjuvants, surfactants, and the like. Such compositions, which may be prepared in any manner known in the art, likewise form part of the present invention.

The composition may also contain other kinds of ingredients such as protective colloids, adhesives, thickeners, thixotropic agents, penetrants, spray oils (especially for mite applications), stabilizers, preservatives (especially mold preservatives), sequestering agents, etc., as well as insecticidal properties. (particularly insecticidal, acaricidal, nematicidal or bactericidal) or other known active ingredients of properties that regulate the growth of plants. More generally, the arylpyrazoles used in the present invention may be combined with any solid or liquid additive equivalent to conventional compounding techniques.

Compositions suitable for agricultural, horticultural and the like use include formulations suitable for use as, for example, sprays, dusts, granules, mists, foams, emulsions, and the like.

The effective amount of the arylpyrazole used in the present invention may vary within a wide range depending on the nature of the pest to be removed or the degree of infection of the crop with the pest, for example. In general, a composition according to the present invention generally comprises from about 0.05 to about 95 (wt.) % of one or more active ingredients according to the present invention, from about 1 to about 95 % of one or more solid or liquid carriers and, optionally, from about 0.1 to about 50% of one or more other compatible ingredients such as surfactants and the like.

In the present invention, the term "carrier" denotes a natural or synthetic, organic or inorganic ingredient with which the active ingredient is combined to facilitate its use, for example in plants, seeds or soil. The carrier should therefore normally be inert and acceptable (eg agronomically acceptable, especially for the treated plant).

Carriers can be solids, for example clays, natural or synthetic silicates, silica, resins, waxes, solid fertilizers (for example ammonium salts), underground natural minerals such as kaolin, clay, talc, chalk, quartz, attapulgite. ), montmorillonite, bentonite or diatomaceous earth, or underground synthetic minerals such as silica, alumina, or silicates, in particular aluminum or magnesium silicates. As solid carriers for granules the following are suitable: crushed or divided natural rocks such as calcite, marble, pumice, sepiolite and dolomite; synthetic granules of organic or inorganic meal; granules of organic material such as sawdust, coconut husks, corn cobs, corn husks or tobacco stalks; porous diatomaceous earth, tricalcium phosphate, powdered cork or adsorbent carbon black; water-soluble polymers, resins, waxes; or solid fertilizer. If desired, the solid composition may contain one or more compatible wetting, dispersing, emulsifying or coloring agents which, when solid, may also act as diluents.

The carrier may also be a liquid, for example: water; alcohols, especially butanol or glycols, as well as ethers or esters thereof, especially methylglycol acetate; ketones, especially acetone, cyclohexanone, methylethylketone, methylisobutylketone, or isophorone; petroleum fractions such as paraffinic or aromatic hydrocarbons, especially xylenes or alkyl naphthalenes; mineral or vegetable oil; aliphatic chlorinated hydrocarbons, especially trichloroethane or methylene chloride; aromatic chlorinated hydrocarbons, especially chlorobenzene; water-soluble or strongly polar solvents such as dimethylformamide, dimethyl sulfoxide, or N-methylpyrrolidone; liquefied gas or the like or a mixture thereof.

Surfactants may be emulsifiers, dispersants or wetting agents in ionic or nonionic form, or mixtures of these surfactants. Among the above, for example, salts of polyacrylic acid, salts of lignosulfonic acid, salts of phenolsulfonic acid or naphthalenesulfonic acid, polycondensates of ethylene oxide with fatty alcohols or fatty acids or fatty esters or fatty amines, substituted phenols (especially alkylphenols) or arylphenol), salts of sulfosuccinic acid esters, taurine derivatives (especially alkyltaurates), phosphoric acid esters of alcohols or polycondensates of ethylene oxide and phenol, esters of fatty acids with polyols, or alcohols of the arylpyrazoles a phosphate, sulfonate or phosphate functional derivative. The presence of one or more surfactants is usually necessary when the active ingredient and/or inert carrier are only slightly or not water-soluble and the carrier agent of the composition for use is water.

The composition of the present invention may additionally contain other additives such as adhesives or colorants. Adhesives such as carboxymethylcellulose or natural or synthetic polymers in the form of powders, granules or lattices such as gum arabic, polyvinyl alcohol or polyvinyl acetate, natural phospholipids such as cephalin or lecithin, or synthetic phospholipids are used in the form of formulations can colorants such as inorganic pigments, for example: iron oxide, titanium oxide or Prussian Blue; organic dyes such as alizarin dyes, azo dyes or metal phthalocyanine dyes; Or it is possible to use salts of micronutrients such as iron, manganese, boron, copper, cobalt, molybdenum or zinc.

Compositions containing arylpyrazoles of the formula (I), or pesticidally acceptable salts, which are applicable for inhibiting arthropod, plant nematode, parasitic or protozoan pests, may also contain potentiating agents (e.g. piperonyl butoxide or sesamex), stabilizing substances, other pesticides, acaricides, plant nematodes, anthelmintic or coccidiosis agents, fungicides (agricultural or veterinary as appropriate, for example benomyl and iprodione), antibacterial agents, arthropods or vertebrates It may contain an attractant or repellent or a pheromone. This may result in the composition exhibiting a spectrum of inhibition potential, resistance, safety, absorption capacity, if desired, of the plague inhibited, or other useful action in the same animal or treated area. Examples of other bactericidal active arylpyrazoles that may be included or used with the compositions of the present invention are: acetate, chlorpyrifos, demeton-S-methyl, disulfotone, etoprophos, phenytrothione, phenami phos, phonophos, isazophos, isopenphos, malathion, monocrotophos, parithione, porate, phosalone, pyrimiphos-methyl, terbuphos, triazophos, cyfluthrin, cypermethrin, delta Metrin, fenpropatrine, fenvalerate, permethrin, tefluthrin, aldicarb, carbosulfan, methomyl, oxamyl, pyrimicarb, bendiocarb, teflubenzuron, dicopol, endosulfan, lindan, benzoximate, cataph, cyhexatin, tetradifone, avermectin, ivermectin, milbemicin, thiophanate, trichlorphone, dichlorbos, diaveridine or dimethriadazole.

For their agricultural application, the arylpyrazoles of formula (I), or pesticidal acceptable salts thereof, are therefore in the form of compositions, usually in various solid or liquid forms.

The solid form of the composition that can be used is a dust powder (the content of the arylpyrazole of formula (I) or a pesticidally acceptable salt thereof is not more than 80%), wettable powders or granules (including water-dispersible granules), especially powders (the above The content of the arylpyrazole of formula (I) or a pesticidally acceptable salt thereof in the wettable powder or granules of , or those obtained by granulation. Solid, homogeneous or heterogeneous compositions, such as granules, pellets, briquettes or capsules, containing at least one arylpyrazole of the formula (I) or a pesticidally acceptable salt thereof, may be formulated in either static water or running water () can be used for long-term treatment. A similar effect can be achieved by rippling or intermittently feeding the water-dispersible concentrates described herein.

Liquid compositions include, for example, aqueous or non-aqueous solutions or suspensions (eg, emulsifiable concentrates, emulsions, fluids, dispersions or solutions) or aerosols. Liquid compositions also include, inter alia, emulsifiable concentrates, dispersions, emulsions, fluids, aerosols, wettables, in the form of aqueous sprays (including low and ultra-low doses) or mists or aerosols, which are liquids or which form a liquid composition upon use. Also included are powders (or powders for spraying), dry fluids or pastes.

Liquid compositions, for example in the form of emulsifiable or soluble concentrates, usually contain from about 5 to about 80% by weight of the active ingredient, whereas ready-to-use emulsions or solutions contain from about 0.01 to about 20% of the active ingredient. Emulsifiable or soluble concentrates may contain, if necessary, from about 2 to about 50% of suitable additives such as stabilizers, surfactants, penetrants, corrosion inhibitors, colorants or adhesives in addition to the solvent. An emulsion of any required concentration, particularly suitable for use in plants and the like, can be obtained by diluting the concentrate with water. These compositions are included within the scope of compositions that can be used in the present invention. Emulsions may exist as water-in-oil or oil-in-water types and may have a thick consistency.

The liquid composition of the present invention may be infested or infested with arthropods (or other pests removed by the arylpyrazoles of the present invention), including storage or processing areas inside buildings, outdoors or indoors, other than for normal agricultural use. It can be used to treat easy incubators or areas, vessels or devices, or still or running water.

All these aqueous dispersions or emulsions or spray mixtures may be used on crops, for example by any suitable means, principally by spraying, usually at a rate of about 100 to about 1,200 liters of spray mixture per hectare, but more depending on the need or technique of use. It can be more or less (eg, low or very low dose). The composition or arylpyrazole according to the present invention is conveniently used for plants, particularly roots or leaves, having pests to be removed. Another method of use of the compositions according to the invention or of the arylpyrazoles is chemigation, ie the addition of a formulation containing the active ingredient to irrigation water. The irrigation may be sprinkler irrigation for foliar pests, or soil irrigation or underground irrigation for soil or systemic pests.

Concentrated suspensions that can be used by spraying do not settle (finely ground), and usually contain from about 10 to about 75% by weight of active ingredient, from about 0.5 to about 30% by weight of surfactant, from about 0.1 to about 10% by weight of the active ingredient. thixotropic agents, from about 0 to about 30% by weight of suitable additives such as antifoaming agents, corrosion inhibitors, stabilizers, penetrants, adhesives, and water as carriers or organic liquids in which little or no active ingredient is dissolved prepared to form a stable fluid product containing Some organic solids or inorganic salts may be dissolved in the carrier to prevent precipitation or water freezing.

Wettable powders (or powders for spraying) typically contain from about 10 to about 80% by weight of active ingredient, from about 20 to about 90% by weight of a solid carrier, from about 0 to about 5% by weight of a wetting agent, and from about 3 to about 10% by weight of a dispersing agent. , and optionally from about 0 to about 80% by weight of one or more stabilizers and/or other additives such as penetrants, adhesives, anti-caking agents, colorants, and the like. To obtain such wettable powders, the active ingredient, together with additional materials which may be impregnated onto the porous filler, are thoroughly mixed in a suitable blender and ground with a mill or other suitable grinder. Thereby, a wettable powder having advantageous wettability and suspendability is obtained. They can be suspended in water at any desired concentration, and this suspension can be used very advantageously, especially for the leaves of plants.

"Water-dispersible granules (WG)" (granules that can be easily dispersed in water) have a composition substantially close to that of a wettable powder. The granules are prepared by wet route (finely divided The active ingredient is brought into contact with an inert filler and small amounts, such as 1 to 20% by weight of water, or otherwise with an aqueous dispersant or binder solution, followed by drying and screening), or the dry route (compacting followed by grinding and screening). ) can be produced by granulating by

The proportions and concentrations of the formulated compositions may vary depending on the method of use or the nature of the composition or its use. Usually, the composition for the removal of arthropods, plant nematodes, parasites or protozoan pests is usually from about 0.00001 to about 95% by weight, preferably from about 0.0005 to about 50% by weight of at least one arylpyrazole of formula (I). or a pesticidally active salt thereof, or the total active ingredient (i.e., together with an arylpyrazole of formula (I) or a pesticidally active salt thereof, other substances toxic to arthropods or plant nematodes, anthelmintic, anti anticoccidial, synergist, trace element or stabilizer). The composition actually used and the proportion of its use will be selected within a range that allows a farmer, livestock farmer, medical practitioner or veterinarian, pest control worker or other skilled in the art to achieve the desired effect.

Solid or liquid compositions for topical use in animals, wood, storage or household products usually contain from about 0.00005 to about 90% by weight, more preferably from about 0.001 to about 10% by weight of at least one aryl of formula (I). pyrazole or a pesticidally active salt thereof. For administration of a solid or liquid composition orally or parenterally, including transdermally, the composition normally comprises from about 0.1 to about 90% by weight of at least one arylpyrazole of formula (I) or its insecticidal active agent. contains salt. Foodstuffs admixed with drugs normally contain from about 0.001 to about 3% by weight of at least one arylpyrazole of formula (I) or a pesticidally active salt thereof. Concentrates or supplements for admixture with food products normally contain from about 5 to about 90% by weight, preferably from about 5 to about 50% by weight of at least one arylpyrazole of formula (I) or a pesticidally active salt thereof. contains Mineral salt licks normally contain from about 0.1 to about 10% by weight of at least one arylpyrazole of formula (I) or a pesticidally active salt thereof.

Dust or liquid compositions for use in livestock, articles, buildings or outdoor areas comprise from about 0.0001 to about 15% by weight, more preferably from about 0.005 to about 2.0% by weight of one or more arylpyrazoles of formula (I) or its pesticidally active salts. A suitable concentration of at least one arylpyrazole of formula (I) or a pesticidal active salt thereof in the treated water is from about 0.0001 ppm to about 20 ppm, more preferably from about 0.001 ppm to about 5.0 ppm, which is It can be used therapeutically with an appropriate number of exposures in aquaculture. The edible bait may contain from about 0.01 to about 5% by weight, preferably from about 0.01 to about 1.0% by weight of at least one arylpyrazole of formula (I) or a pesticidally active salt thereof.

When administered to vertebrates parenterally, orally or by transdermal or other means, the dosage of the arylpyrazole of formula (I) or a pesticidally active salt thereof depends on the type, age or health of the vertebrate, and the arthropod. It depends on the nature of the animal, parasitic or protozoan pest and the actual or potential prevalence. For continuous drug treatment, a single dose of from about 0.1 to about 100 mg, preferably from about 2.0 to about 20.0 mg per kg of body weight of animal per day or from about 0.01 to about 20.0 mg per kg of body weight of animal per day, preferably Multiple administrations of preferably about 0.1 to about 5.0 mg are generally suitable for oral or parenteral administration. By the use of sustained release formulations or devices, the combined daily doses required for one month may be administered to the animal at one time.

The composition of Examples 2A-2M below contains, as an active ingredient, an arylpyrazole of formula (I) or a pesticidally active salt thereof, as an active ingredient, as described in the Preparation Examples, arthropods, in particular ticks or pests, plants The composition used for the removal of a nematode, or a parasite or a protozoan pest is illustrated. Each of the compositions described in Examples 2A-2M can be diluted into a dispersible composition to a concentration suitable for field use. The general chemical descriptions of the components (the following percentages are all weight percentages) used in the compositions of Examples 2A-2M exemplified below are as follows:

trade name chemical technology

Ethylan BCP Nonylphenol Ethylene Oxide Condensate

Soprophor BSU Tristyrylphenol Ethylene Oxide Condensate

70% w/v solution of Arylan CA calcium dodecylbenzenesulfonate

Solvesso 150 light C₁₀ aromatic solvents

Arylane S Sodium Dodecylbenzenesulfonate

Darvan No. 2 Sodium Lignosulfonate

Celite PF Synthetic Magnesium Silicate Carrier

Sopropon T36 Sodium Salt of Polycarboxylic Acid

Rhodigel 23 Polysaccharide Xanthan Gum

Bentone 38 Organic Derivative of Magnesium Montmorillonite

Aerosil Microfine Silicon Dioxide

Example 2A

An aqueous concentrate having the following composition is prepared:

7% active ingredient

Ethylane BCP 10%

N-methylpyrrolidone 83%

The active ingredient is added to a solution of ethylan BCP dissolved in a portion of N-methylpyrrolidone, and heated and stirred until dissolved. Add the remaining solvent to the obtained solution to make the final volume.

Example 2B

An emulsifiable concentrate (EC) having the following composition is prepared:

25% active ingredient (maximum)

Soprophor BSU 10%

Aryllan CA 5%

50% N-methylpyrrolidone

Solvesso 150 10%

The first three components are dissolved in N-methylpyrrolidone, and Solvesso 150 is added thereto to make the final volume.

Example 2C

A wettable powder (WP) having the following composition is prepared:

40% active ingredient

Aryllan S 2%

Darban 2 5%

Celite PF 53%

The ingredients are mixed and ground in a hammer-mill to a powder having a particle size of less than 50 microns.

Example 2D

An aqueous-flowable formulation having the following composition is prepared:

Active ingredient 40.00%

Ethylane BCP 1.00%

Soprophone T360 0.20%

Ethylene glycol 5.00%

Rhodigel 230 0.15%

Water 53.65%

The ingredients are intimately mixed and ground in a bead mill until the average particle size is less than 3 microns.

Example 2E

An emulsifiable suspension concentrate having the following composition is prepared:

active ingredient 30.0%

Ethylane BCP 10.0%

Benton 38 0.5%

Solvesso 150 59.5%

The ingredients are intimately mixed and ground in a bead mill until the average particle size is less than 3 microns.

Example 2F

To prepare water-dispersible granules having the following composition:

30% active ingredient

Darban 2 15%

Aryllan S 8%

Celite PF 47%

The above ingredients are mixed, pulverized in a fluid-energy mill, and then granulated by spraying with water (10% or less) in a rotating pelletizer. The obtained granules are dried in a fluid-bed dryer to remove excess water.

Example 2G

A dust powder having the following composition is prepared:

1 to 10% active ingredient

99 to 90% of ultrafine talc powder

The ingredients are intimately mixed and, if necessary, further ground to a fine powder. Arthropods can be removed by oral ingestion by applying the powder to arthropod-infested areas, such as garbage dumps, storage items or household items, or animals infested or at risk of infestation with arthropods.

Example 2H

An edible bait having the following composition is prepared:

Active ingredient 0.1 to 1.0%

Flour 80%

Molasses 19.9 to 19%

The ingredients are intimately mixed and, if necessary, further milled to form the bait. This edible bait eliminates arthropods by oral ingestion, by spraying them in areas infested with arthropods such as ants, grasshoppers, cockroaches or flies, such as in kitchens, hospitals or shops, in areas inside or outside household or industrial buildings. can do.

Example 2I

A solution formulation having the following composition is prepared:

15% active ingredient

dimethyl sulfoxide 85%

The active ingredient is dissolved in dimethyl sulfoxide with mixing and/or heating if necessary. This solution can be used transdermally, such as by pour-on application to arthropod-infested livestock, or sterilized by filtration through a polytetrafluoroethylene membrane (pore size of 0.22 μm) and weighed 100 animals. It can be used by parenteral injection at a rate of 1.2 to 12 ml per kg.

Example 2J

A wettable powder having the following composition is prepared:

50% active ingredient

Ethylane BCP 5%

Aerosil 5%

Celite PF 40%

Ethylane BCP is absorbed into the Aerosil phase, mixed with other ingredients, and pulverized in a hammer-mill to make a wettable powder, then diluted with water to adjust the concentration of active arylpyrazole to 0.001 to 2% by weight, and to dilute larvae or plants Arthropods, parasites by spraying in areas infested with arthropods such as nematodes, or by spraying on livestock infested or at risk of infestation with arthropods, parasites or protozoa, by immersing livestock in this solution, or by oral administration by drinking water; Alternatively, protozoa can be eliminated.