CZ536088A3 - Method of fighting insects, nematodes and mites, process of protecting growing plants, insecticidal, acaricidal and nematocidal preparation, arylpyrrole compounds as well as method and intermediates for preparing thereof - Google Patents

Description

The invention relates to a method for controlling insects, nematodes and mites and to a method of protecting growing plants from attack by these pests using certain arylpyrrole compounds. Further, the invention relates to an insecticidal, acaricidal and nematicidal composition based on these compounds, to novel arylpyrrole compounds per se, and to a process and intermediates for making some of these novel arylpyrrole compounds. The aforementioned arylpyrrole compounds are very effective insecticidal, acaricidal and nematicidal agents useful for controlling insects, mites and nematodes and for protecting agronomic crops, whether growing or harvested, from damage by these pests.

SUMMARY OF THE INVENTION

In one aspect, the present invention provides a method for controlling insects, nematodes and mites, comprising contacting insects, nematodes and mites with the insecticidally, nematocidally or acaricidally effective amount of an arylpyrrole compound in a place where they are multiplied. of formula I

where

X represents a hydrogen, fluorine, chlorine, bromine or iodine atom or a trifluoromethyl group;

Y is fluorine, chlorine, bromine or iodine, trifluoromethyl or cyano;

W is cyano or nitro;

A represents a hydrogen atom, a C 1 -C 4 alkyl group optionally substituted by one to three halogen atoms, one hydroxy group, one C 1 -C 4 alkoxy group or one C 1 -C 4 alkylthio group, one phenyl group optionally substituted by an alkyl group C 1 -C 3, C 1 -C 3 alkoxy or C 1 -C 3 halogen, one phenoxy optionally substituted with 1 to 3 halogen atoms or one benzyloxy optionally substituted with one halogen, furthermore C 1 -C 4 alkoxycarbonylmethyl C 3 -C 4 alkenyl optionally substituted with 1 to 3 halogen atoms, cyano, C 3 -C 4 alkynyl optionally substituted with one halogen atom, C 1 -C 4 dialkylaminocarbonyl in each alkyl moiety, or cycloa (C 4 -C 6) alkylaminocarbonyl in the cycloalkyl moiety;

L is hydrogen, fluorine, chlorine or bromine; and

M and R are each independently hydrogen, C 1 -C 3 alkyl, C 1 -C 3 alkoxy, C 1 -C 3 alkylthio, C 1 -C 3 alkylsulfinyl, C 1 -C 3 alkylsulfonyl 3 carbon atoms, cyano, fluorine, chlorine, bromine or iodine, nitro, trifluoromethyl, R ₁ CF ₂ Z, R ₂ CO or NR ₃ R ₄ , or M and R, attached at adjacent positions together with carbon atoms to which they are attached may form a ring in which MR represents a residue

-CCH 2 O-, -OCl 2 O- or

Z is S (O) _n or oxygen;

R 6 represents a hydrogen atom, a fluorine atom, a difluoromethyl group, a fluorochloromethyl group or a trifluoromethyl group;

R ₂ represents an alkyl group having 1-3 carbon atoms, alkoxy having 1 to 3 carbon atoms or a radical RR3R4 ΐ

R ₃ represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms;

R 4 is hydrogen, C 1 -C 3 alkyl or R ₅ CO;

R ₅ represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms and

I n is a number of 0, 1 or 2.

According to a second aspect, the invention also provides a method of protecting growing plants from insect attack,

Nematodes and mites, characterized in that an insecticidally, nematocidally or acaricidally effective amount of an arylpyrrole compound as defined above is applied to the leaves of these plants or to the soil or water in which they grow.

The invention also relates to an insecticidal, acaricidal and nematicidal composition comprising, as active ingredient, an arylpyrrole compound as defined above.

A further object of the invention are novel arylpyrrole compounds of formula I wherein the individual general symbols. are as defined above, but X is not hydrogen.

C 4 -C 6 cycloalkylaminocarbonyl refers to a C 4 -C 6 cycloalkylamino group directly attached to the carbonyl group via a nitrogen atom.

A preferred class of novel arylpyrroles of the present invention are those of Formula IIt

in which

A, L, M, R, W, X and Y are as defined above.

A further preferred class of novel arylpyrroles according to the invention are compounds of formula III

(III) wherein

A, L, M, R, W, X and Y are as defined above.

A further group of preferred arylpyrrols according to the invention are compounds of formula IV

in which

A, L, M, R, W, X and 1 are as defined above.

Yet another group of preferred arylpyrrols of the invention corresponds to formula V

in which

A, L, M, R, W, X, and T are as defined above, and further have the general formulas (VI) and (VII)

(VI)

(VII) in which:

A, L, M, R, W, X and Y are as defined above.

Preferred arylpyrroles of the formula I according to the invention are those in which A represents a hydrogen atom or a (C1-C4) alkoxymethyl group, W represents a cyano or nitro group, L represents a hydrogen or fluorine atom,

X and Y are each independently chlorine, bromine or trifluoromethyl, M is hydrogen, fluorine, chlorine or bromine and R is fluorine, chlorine or bromine, trifluoromethyl or trifluoromethoxy.

Preferred compounds of formula II which are particularly effective as insecticidal, acaricidal and / or nematicidal agents are those wherein A is hydrogen or C1-C4alkoxymethyl in the alkoxy moiety, L is hydrogen, M R is fluorine, chlorine or bromine, trifluoromethyl or trifluoromethoxy, W is cyano, and X and Y are each independently chlorine, bromine or trifluoromethyl.

in

Other compounds of the formula II which are highly effective as insecticides, acaricides and / or nematicides are those in which A represents a hydrogen atom or a (C1-C4) alkoxymethyl group, L represents a hydrogen atom, M represents a hydrogen, fluorine, chlorine or R is fluorine, chlorine or bromine, trifluoromethyl or trifluoromethoxy, W is nitro, and X and Y are each independently bromo or trifluoromethyl.

Illustrative examples of the insecticidally acaricidally and nematocidally active arylpyrrols of the present invention include the following compounds:

4,5-dichloro-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile,

4,5-dichloro-2- [p- (trifluoromethoxy) phenyl] pyrrole-3-carbonitrile,

4-bromo-5-chloro-2- (p-chlorophenyl) pyrrole-3-carbonitrile,

5-bromo-4-chloro-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile,

4,5-dichloro-2- (o-chlorophenyl) pyrrole-3-carbonitrile,

2- (p-bromophenyl) -4,5-dichloropyrrole-3-carbonitrile,

4,5-dichloro-2- (α, α, α-trifluoro-p-tolyl) pyrrole-3-carbonitrile,

4,5-dibromo-2- (α, α, α-trifluoro-p-tolyl) pyrrole-3-carbo nitrile,

4,5-dibromo-2- (o-chlorophenyl) pyrrole-3-carbonitrile,

4,5-dibromo-2- (p-chlorophenyl) pyrrole-3-carbonitrile,

4,5-dichloro-2- (2,4-dichlorophenyl) pyrrole-3-carbonitrile,

4,5-dibromo-2- (2,4-dichlorophenyl) pyrrole-2-carbonitrile,

2,3-dibromo-4-nitro-5-phenylpyrrole,

2- (p-bromophenyl) -4,5-dichloro-3-nitropyrrole,

2,3-dichloro-4-nitro-5- (α, α, α-trifluoro-p-tolyl) pyrrole,

4,5-dichloro-2- (m-chlorophenyl) pyrrole-3-carbonitrile,

4,5-dichloro-2- (p-chlorophenyl) pyrrole-3-carbonitrile,

4,5-dichloro-2-phenylpyrrole-3-carbonitrile,

2,3-dichloro-5- (p-chlorophenyl) -4-nitropyrrole,

2-bromo-3-chloro-5- (p-chlorophenyl) -4-nitropyrrole,

2,3-dibromo-5- (p-chlorophenyl-4-nitropyrrole),

2,3-Dichloro-4-nitro-5-phenylpyrrole

3-bromo-2-chloro-4-nitro-5- (α, α, α-trifluoro-p-tolyl) pyrrole,

5-chloro-2- (3,4-dichlorophenyl) -1-methoxymethyl) -4- (trifluoromethyl) pyrrole-3-carbonitrile, bromo-2- (m-fluorophenyl) -3-nitro-4- (trifluoromethyl) pyrrole ,

2- (p-chlorophenyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile,

3-bromo-5- (m-fluorophenyl) -4-nitro-2- (trifluoromethyl) pyrrole;

4-bromo-2- (p-chlorophenyl) -1- (ethoxymethyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile,

4-chloro-2- (3,5-dichloro-4-methylphenyl) -3-nitro-5- (trifluoromethyl) pyrrole,

2- (2-bromo-4-chlorophenyl) -1- (2-propynyl) -4,5-bis- (trifluoromethyl) pyrrole-3-carbonitrile,

2- (2,5-difluorophenyl) -3-nitro-4,5-his- (trifluoromethyl) pyrrole,

- 13 5- (ρ- (trifluoromethoxy) phenyl) pyrrole-2,4-dicarbonitrile,

5- (p-dimethylaminophenyl) -4-nitropyrrole-2-carbonitrile,

3-bromo-5- (p-chlorophenyl) pyrrole-2,4-dicarbonitrile,

4-bromo-2- (p-chlorophenyl) -5-nitropyrrole-3-carbonitrile,

5- (p-methylthiophenyl) -3- (trifluoromethyl) pyrrole-2,4-dicarbonitrile,

1-allyl-4-nitro-5- (α, α, ω-trifluoro-p-tolyl) -3- (trifluoromethyl) pyrrole-2-carbonitrile,

4-chloro-2- (p-chlorophenyl) pyrrole-3-carbonitrile,

2- (m-methanesulfonylphenyl) -4- (trifluoromethyl) pyrrole-3-carbonitrile,

2- (3-chloro-4-methylphenyl) -1-methyl-3-nitro-4- (trifluoromethyl) pyrrole,

2-phenylpyrrole-3,4-dicarbonitrile,

5- (p-ethanesulfinylphenyl) -4-nitropyrrole-3-carbonitrile,

2-bromo-5-phenylpyrrole-3,4-dicarbonitrile,

2-chloro-5- (3,5-dichlorophenyl) -4-nitropyrrole-3-carbonitrile,

1-Benzyl-4-nitro-5- (p-chlorophenyl) -2- (trifluoromethyl) pyrrole-3-carbonitrile,

2-chloro-5- (m-bromophenyl) pyrrole-3-carbonitrile,

2-bromo-1- (p-chlorophenoxy) methyl-5- (p-chlorophenyl) -3-nitropyrrole,

2,4-dibromo-5-phenylpyrrole-3-carbonitrile,

5- (p-bromophenyl) -2,4-dichloro-3-nitropyrrole,

2-bromo-5- (3-bromo-4-methylphenyl) -1- (n-propyloxy) methyl-4- (trifluoromethyl) pyrrole-3-carbonitrile,

2-bromo-5- (p-chlorophenyl) -3-nitro-4- (trifluoromethyl) pyrrole,

5-C 1- (difluoromethoxy) phenyl] -2- (trifluoromethyl) pyrrole-3-carbonitrile,

5- (2,3-dichlorophenyl) -1-methoxymethyl-3-nitro-2- (trifluoromethyl) pyrrole,

4-chloro-5- (O-naphthyl) -2- (trifluoromethyl) pyrrole-3-carbonitrile,

3-bromo-2- (3,4-dichlorophenyl) -4-nitro-5- (trifluoromethyl) pyrrole,

5- (2-bromo-5-ethylphenyl) -2,4-bis- (trifluoromethyl) pyrrole-3-carbonitrile, 1-ethyl-2- (p-fluorophenyl) -4-nitro-3,5-bis- ( Trifluoromethyl) pyrrole

1-E (2,6-dichlorophenoxy) methyl] -5- (m-chlorophenyl) pyrrole-2,3-dicarbonitrile,

3-nitro-5- (α, α, α-trifluoro-p-tolyl) pyrrole-2-carbonitrile,

4-chloro-5- (4-chloro-2-methylphenyl) pyrrole-2,3-dicarbonitrile,

4-bromo-5- (3,4-dibromophenyl) -2-nitropyrrole-3-carbonitrile,

1-E (1-methoxy) ethyl] -5- (p-chlorophenyl) -4- (trifluoromethyl) pyrrole-2,3-dicarbonitrile,

5- (p-isopropylphenyl) -2-nitro-4- (trifluoromethyl) pyrrole-3-carbonitrile,

4-chloro-5- (3,4-difluoromethylenedioxyphenyl) pyrrole-3-carbonitrile,

3-bromo-2- (3-chloro-4-cyanophenyl) -4-nitropyrrole,

1- C (3,4-dichlorobenzyloxy) methyl] -2- (m-bromophenyl) pyrrole-4-carbonitrile,

2- (3,5-dichloro-4-methylphenyl) -4-nitro-3-trifluoromethylpyrrole,

2-phenylpyrrole-3,4-dicarbonitrile,

2- (2-bromo-4-chlorophenyl) -4-nitropyrrole-3-carbonitrile,

2-bromo-5-phenylpyrrole-3,4-dicarbonitrile,

5-chloro-2- (3,4-dibromophenyl) -1-methyl-4-nitropyrrole-3-carbonitrile,

2- (p-chlorophenyl-5- (trifluoromethyl) pyrrole-3,4-dicarbonitrile,

2- (o-bromophenyl) -4-nitro-5- (trifluoromethyl) pyrrole-3-carbonitrile,

3-bromo-5- (3-chloro-4-methoxy) pyrrole-2-carbonitrile,

3-bromo-5- (m-bromophenyl) -2-nitropyrrole,

- 17 3,4-dibromo-5- (3,4-dichlorophenyl) pyrrole-2-carbonitrile,

2- (3-chloro-4-cyanophenyl) -5-nitro-3,4-dichloropyrrole,

3-chloro-1- (p-methoxybenzyl) -5- (3,4-difluorophenyl) -4- (trifluoromethyl) pyrrole-2-carbonitrile,

3-bromo-5- (3,5-dibromo-p-tolyl) -2-nitro-4- (trifluoromethyl) pyrrole,

1- (2,3,3-trichlorallyl) -5- (p-chlorophenyl) -3- (trifluoromethyl) pyrrole-2-carbonitrile,

2- (p-Jphenyl) -5-nitro-4- (trifluoromethyl) pyrrole,

4-chloro-5- (m-isopropylphenyl) -3- (trifluoromethyl) pyrrole-2-carbonitrile,

3-bromo-1-methyl-2- (3-fluoro-4-methylphenyl) -2-nitro-3- (trifluoromethyl) pyrrole,

5- (p-bromophenyl) -1-isopropyl-3,4-bis- (trifluoromethyl) pyrrole-2-carbonitrile,

2- (3,4-dichloro-4-methylthio) -5-nitro-3,4-bia- (trifluoromethyl) pyrrole,

5- (m-difluoromethoxyphenyl) pyrrole-2,3-dicarbonitrile,

5- (3-bromo-4-cyanophenyl) -2-nitropyrrole-3-carbonitrile,

4-chloro-1-methoxymethyl-5- (p-bromophenyl) pyrrole-2,3-dicarbonitrile,

4-bromo-5- (2,6-dichloro-4-methylthio) -2-nitropyrrole-3-carbonitrile,

1- C (p-bromophenoxy) methyl] -5- (m-trifluoromethyl) -4- (trifluoromethyl) pyrrole-2,3-dicarbonitrile,

5- (α-naphthyl) -2-nitro-4- (trifluoromethyl) pyrrole-3-carbonitrile,

4-bromo-5- (3-bromo-4-trifluoromethylphenyl) pyrrole-2-carbonitrile,

3-chloro-2- (2,3-dichlorophenyl) -5-nitropyrrole,

5- (m-cyanophenyl) -3- (trifluoromethyl) pyrrole-2-carbonitrile,

2- (3-bromo-4-iopropoxy) -5-nitro-3- (trifluoromethyl) pyrrole,

5- (p-chlorophenyl) pyrrole-2,4-dicarbonitrile,

2- (3,4-dichlorophenyl) -5-nitropyrrole-3-carbonitrile,

3-bromo-5- (3,4-dichlorophenyl) pyrrole-2,4-dicarbonitrile,

4-bromo-2- (3,4-dichlorophenyl) -5-nitropyrrole-3-carbonitrile,

5- (3,4-dibromophenyl) -3-trifluoromethyl) pyrrole-2,4-dicarbonitrile,

2- (t-chlorophenyl) -5-nitro-4- (trifluoromethyl) pyrrole-3-carbonitrile,

5-bromo-3- (3,5-dichloro-4-difluoromethoxyphenyl) pyrrole-2-carbonitrile,

2-bromo-4- (2,5-dibromophenyl) -5-nitropyrrole,

2,3-dibromo-4- (p-chlorophenyl) pyrrole-5-carbonitrile,

2,3-Dichloro-4- (3,5-difluorophenyl) -5-nitropyrrole

5-bromo-3- (p-chlorophenyl) -1-hydroxyethyl-4- (trifluoromethyl) pyrrole-2-carbonitrile,

2-chloro-5-nitro-3- (trifluoromethyl) -4- (m-trifluoromethylphenyl) pyrrole,

3- (3-bromo-4-chlorophenyl) -5- (trifluoromethyl) pyrrole-2-carbonitrile,

3- (3-chloro-4-fluorophenyl) -2-nitro-5- (trifluoromethyl) pyrrole,

4-bromo-3- (p-chlorophenyl) -1-methylthiomethyl-5- (trifluoromethyl) pyrrole-2-carbonitrile,

3- (4-bromo-3-cyanophenyl) -4-chloro-2-nitro-5- (trifluoromethyl) pyrrole,

4- (p-chlorophenyl) -2,3-bis- (trifluoromethyl) pyrrole-2-carbonitrile,

3- (2,3-dichlorophenyl) -2-nitro-4,5-bis- (trifluoromethyl) pyrrole

3- (3,4-dichlorophenyl) pyrrole-2,5-dicarbonitrile,

4- (2-bromo-4-methylphenyl) -5-nitropyrrole-2-carbonitrile,

3-bromo-4- (3,5-dichloro-4-methylthiophenyl) pyrrole-2,5-dicarbonitrile,

4- (m-bromophenyl) -3-chloro-5-nitropyrrole-2-carbonitrile,

3- (p-acetamidophenyl) -4- (trifluoromethyl) pyrrole-2,5-dicarbonitrile,

4- (m-bromophenyl) -5-nitro-3- (trifluoromethyl) pyrrole-2-carbonitrile,

4-chloro-3- (3,4-dichlorophenyl) -1- (1-propenyl) pyrrole-2-carbonitrile,

3-bromo-4- (p-dimethylaminophenyl) -5-nitropyrrole,

1- (3,4-dichlorobenzyl) -3- (p-chlorophenyl) -4- (trifluoromethyl) pyrrole-2-carbonitrile,

2-nitro-3- (p-tetrafluoroethoxyphenyl) -4- (trifluoromethyl) pyrrole,

3- (3-bromo-4-isopropylphenyl) pyrrole-2,4-dicarbonitrile,

4- (p-ethylsulfonylphenyl) -5-nitropyrrole-3-carbonitrile;

5-bromo-1- (2-methoxyethyl) -4- (2,4,6-trichlorophenyl) pyrrole-2,4-dicarbonitrile,

2-chloro-4- (2,3-dichlorophenyl) -5-nitropyrrole-3-carbonitrile,

3- (p-fluorophenyl) -5- (trifluoromethyl) pyrrole-2,4-dicarbonitrile,

4- (p-iodophenyl) -5-nitro-2- (trifluoromethyl) pyrrole-3-carbonitrile,

5-chloro-4- [p- (N-methylacetamido) phenyl] pyrrole-2-carbonitrile,

5-bromo-4- (o-bromophenyl) -1-propargylpyrrole-2-carbonitrile,

2-bromo-3- (o-bromophenyl) -5-nitropyrrole,

4- (p-chlorophenyl) -3,5-dichloro-1- (2,3,3-trichlorallyl) pyrrole-2-carbonitrile,

3-bromo-5-chloro-4- (p-chlorophenyl) -2-nitropyrrole,

5-bromo-4-C- (2,2-dichloro-1,1-difluoroethoxy) phenyl] -3- (trifluoromethyl) pyrrole-2-carbonitrile,

2-chloro-3- (2-bromo-4-ethylthiophenyl) -5-nitro-4- (trifluoromethyl) pyrrole

3- (3-bromo-4-acetylphenyl) -5- (trifluoromethyl) pyrrole-2-carbonitrile, 1-cyano-3- (3,4-dibromophenyl) -5-nitro-2- (trifluoromethylpyrrole),

3-bromo-1-methoxymethyl-4- (m-trifluoromethyl) -5- (trifluoromethyl) pyrrole-2 carbonitrile,

3- (p-chlorophenyl) -4-iodo-5-nitro-2- (trifluoromethyl) pyrrole,

4- (p-bromophenyl) -1 - [(1-ethoxy) ethyl] -3,5-di- (trifluoromethyl) pyrrole-2-carbonitrile,

3- (2-bromo-4-methoxyphenyl) -5-nitro-2,4-di- (trifluoromethyl) pyrrole,

3- (p-chlorodifluoromethoxyphenyl) pyrrole-2,5-dicarbonitrile,

2- (p-isobutyrylaminophenyl) -5-nitropyrrole-2-carbonitrile,

3-bromo-4- (3,4-dimethoxyphenyl) pyrrole-2,5-dicarbonitrile,

4-chloro-3- (p-chlorophenyl) -1-isopropyloxycarbonylmethyl) -5-nitropyrrole-2-carbonitrile,

3- (o-Bronphenyl) -4- (trifluoromethyl) pyrrole-2,5-dicarbonitrile,

1- (2-chloroethyl) -3- (3,4-dichlorophenyl) -4- (trifluoromethyl) pyrrole-2-carbonitrile,

4- (4-bromo-3-trifluoromethoxyphenyl) -3-chloropyrrole-2-carbonitrile,

3-bromo-4- (2,4-dichlorophenyl) -1-isopropyl-2-nitropyrrole,

4- (3-methoxy-4-cyanophenyl) -3- (trifluoromethyl) pyrrole-2-carbonitrile,

1- (3,4-dichlorobenzyl) -4- (2-methyl-4-iodophenyl) -2-nitro-3-trifluoromethylpyrrole,

1-methyl-4-C 3,5-di- (trifluoromethyl) phenyl] pyrrole-2,3-dicarbonitrile,

4- (3,4-dichlorophenyl) -2-nitropyrrole-3-carbonitrile,

4- (m-bromophenyl) -1-carbomethoxymethyl-5-chloropyrrole-2,3-dicarbonitrile,

- bromo-4- (2,6-dichloro-4-methanesulfinylphenyl-2-nitropyrrole-3-carbonitrile),

4- (p-chlorophenyl) -1- (2,2,2-trifluoroethyl) -5- (trifluoromethyl) pyrrole-2,3-dicarbonitrile,

4- (3,5-dichlorophenyl) -2-nitro-5- (trifluoromethyl) pyrrole-3-carbonitrile,

2-chloro-4- (3-chloro-4-N-methylacetamidophenyl) pyrrole-3-carbonitrile,

2-bromo-4- (3-bromo-4-n-propylphenyl) -3-nitropyrrole,

2,5-dichloro-4- (3,5-dichloro-4-methylthiophenyl) pyrrole-3-carbonitrile,

2,5-dibromo-1- (2,4-dibromophenoxymethyl) -3- (p-chlorophenyl-4-nitropyrrole),

4- (3-bromo-4-cyanophenyl) -2-chloro-5- (trifluoromethyl) pyrrole-3-carbonitrile,

2-bromo-1-methyl-3-nitro-4- (α, α, α-trifluoro-p-tolyl) pyrrole,

4- (p-chlorophenyl) -1- (n-butyloxymethyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile,

4- (3,4-methylenedioxyphenyl) -3-nitro-2- (trifluoromethyl) pyrrole,

5-chloro-4- (3-chloro-4-trifluoromethoxyphenyl) -2- (trifluoromethyl) pyrrole-3-carbonitrile,

2-bromo-3- (3,4-dichlorophenyl) -1-ethylthiomethyl-4-nitro-5- (trifluoromethyl) pyrrole;

4- (p- (tetrafluoroethoxy) phenyl] -2,5-di- (trifluoromethyl) pyrrole-3-carbonitrile,

3- (3-bromo-4-acetoxyphenyl) -1- (3,4-dichlorophenoxymethyl) -4-nitro-2,5-di- (trifluoromethyl) pyrrole,

4- (ρ-bromophenyl) -1- (2-methoxy) ethyl] pyrrole-2,3-dicarbonitrile,

4- (m-isopropionamidophenyl) -3-nitropyrrole-2-carbonitrile,

5-bromo-4- (2-chloro-4-methylthio) pyrrole-2,3-dicarbonitrile,

5-chloro-4- (p-chlorophenyl) -1-hydroxyethyl-3-nitropyrrole-2-carbonitrile,

4- (3,5-dibromo-4-cyanophenyl) -5- (trifluoromethyl) pyrrole-2,3-dicarbonitrile,

4- (4-chloro-2-methylphenyl) -1-isopropylthiomethyl-3-nitro-5- (trifluoromethyl) pyrrole-2-carbonitrile,

5-bromo-4- (3,4-dichlorophenyl) -1- (difluoromethyl) pyrrole-3-carbonitrile,

2-chloro-3- (m-difluoromethoxyphenyl) -4-nitropyrrole, 1- (2,4-dibromophenoxymethyl) -4- (m-chlorophenyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile,

3- (3-bromo-4-ethoxy) -4-nitro-2- (trifluoromethyl) pyrrole,

3- (2,4,6-trichlorophenyl) pyrrole-2,4-dicarbonitrile,

3- (4-bromo-3-chlorophenyl) -1- (difluoromethyl) -4-nitropyrrole-2-carbonitrile,

- 5-bromo-3- (p-chlorophenyl) -1- (isobutyloxymethyl) pyrrole-3-carbonitrile,

3- (4-bromo-3-methylphenyl) -5-chloro-4-nitropyrrole-2-carbonitrile,

3- (2-naphthyl) -5- (trifluoromethyl) pyrrole-2,4-dicarbonitrile,

3- (3-cyano-4-methylphenyl) -1-methyl-4-nitro-5- (trifluoromethyl) pyrrole-2-carbonitrile,

2,3-dichloro-5- (3,4-dichlorophenyl) -4-nitropyrrole,

2- (3,5-dibromo-4-ethoxyphenyl) -4,5-dichloropyrrole-3-carbonitrile,

2,3-dihloro-4-nitro-5- (2,4,6-trifluorophenyl) -4-nitropyrrole,

4,5-dibromo-2- (2,3, β-trifluorophenyl) -3-carbonitrile,

4,5-dichloro-2- 3,4-dichlorophenyl) -1- (ethoxymethyl) pyrrole-3-carbonitrile,

4,5-dibromo-1-methyl-2- (α, α, α-trifluoro-p-tolyl) pyrrole-3-carbonitrile,

4,5-dichloro-2- (3,4-dichlorophenyl) -1-ethylpyrrole-3-carbonitrile,

2,3-dichloro-4-nitro-5- [p- (trifluoromethoxy) phenyl] pyrrole,

4,5-dichloro-2- [m- (trifluoromethoxy) phenyl] pyrrole-3-carbonitrile,

4,5-dichloro-2- (3,4-dichlorophenyl) -1-methylpyrrole-3-carbonitrile,

2,3-dichloro-5- (p-chlorophenyl) -1-methyl-4-nitropyrrole,

4-bromo-5-chloro-2- (p-chlorophenyl) -1-methylpyrrole-3-carbonitrile,

5-chloro-2- (3,4-dichlorophenyl) -4-fluoropyrrole-3-carbonitrile,

2-bromo-5- (p-chlorophenyl) -1- (ethoxymethyl) -4-fluoropyrrole-3-carbonitrile,

3-bromo-5- (p-chlorophenyl) -2-fluoro-4-nitropyrrole.

α- (2,2-dialkoxyethylamino) -β-cyanethylene and α- (2,2-dialkoxyethylamino) -3-nitrostyrene compounds in which each alkoxy moiety each contain from 1 to 4 carbon atoms correspond to the following general formula

in which

Alk represents an alkyl group having 1 to 4 carbon atoms,

W is cyano or nitro,

L is hydrogen, fluorine, chlorine or bromine; and

M and R beech. each independently represents a hydrogen atom, a C1-C3 alkyl group, a C1-C3 alkoxy group, a C1-C3 alkylthio group, a C1-C3 alkylsulfinyl group, a C1-C3 alkylsulfonyl group , cyano, fluorine, chlorine, bromine, iodine, nitro, trifluoromethyl, a radical of formula ^ 1 ^ 2 ^, ^not bo NR ^ R ^ or M and R are bonded at adjacent positions together with the carbon atoms to which they are attached may form a ring in which MR represents a residue

-CH2O-, -OCF2O- or

OF

R 11 represents S (O) _n or oxygen, represents a hydrogen atom, a fluorine atom, a difluoromethyl group, a fluorochloromethyl group or a trifluoromethyl group,

R,

R,

R _c is C 1 -C 3 alkyl, C 1 -C 3 alkoxy or NR 4 R 6 is hydrogen or C 1 -C 3 alkyl, C 1 -C 3 alkyl carbon atoms or the radical R @ 6 CO, represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms and is a number of 0, 1 or 2.

A preferred group of β-substyrene compounds of the invention are those compounds of the above formula wherein W is cyano, L is hydrogen, chlorine or bromine, M is hydrogen, fluorine, chlorine or bromine or methoxy and R is hydrogen, fluorine, chlorine or bromine, trifluoromethyl, nitro, trifluoromethoxy or methoxy, or M and R attached at adjacent positions together with the carbon atoms to which they are attached may form a ring in which MR is a radical of the formula

Another preferred class of β-substyrene compounds of the invention are those compounds of the above formula wherein W is nitro,

L is hydrogen, chlorine or bromine, M is hydrogen, fluorine, chlorine or bromine or methoxy and R is hydrogen, fluorine, chlorine or bromine, trifluoromethyl, nitro, trifluoromethoxy or methoxy, or M and R are attached at adjacent positions, together with the carbon atoms to which they are attached, may form a ring in which MR is a radical of formula

While these compounds of the invention are referred to above as β-cyanstyrenes and β-nitrostyrenes, they may also be referred to as dialkylacetals.

Some of the preferred dialkylacetals of the invention are (E) and (Z).

(1) p-chloro-β-E (formylmethyl) amino] cinnamonitrile-diethyl acetal;

2) β - [(formylmethyl) amino] -3,4-dimethoxycinnamonitrile diethyl acetal,

(3) (Z) -methyl- (2-cyano-1 - [(formylmethyl) amino] vinyl) benzoate diethyl acetal;

(4) (Z) -3 - [(formylmethyl) amino] -1-naphthalenacrylonitrile diethyl acetal;

(5) (Z) - [beta] - (formylmethyl) amino] -p-methylcinnamonitrile diethyl acetal,

- 33 (6) N- (formylmethyl) -p-methyl-α- (nitromethylene) benzylamine diethyl acetal,

7) N- (formylmethyl) -3,4-dimethoxy-α- (nitromethylene) benzylamine diethyl acetal;

(8) N- (formylmethyl) -α- (nitromethylene) -2-naphthalenmethylamine diethyl acetal;

(9) methyl p- (α - [(formylmethyl) amino] -β-nitrovinyl] benzoate-p-diethyl acetal;

(10) N- (formylmethyl) -3,4-dimethoxy-α- (nitromethylene) benzylamine dimethylacetal;

(11) (E) and (Z) p-chloro-3 - [(formylmethyl) amino] cinnamonitrile dimethylacetal,

12) β - [(formylmethyl) amino] -3,4-dimethoxycinnamonitrile dimethylacetal,

13) 3,4-dichloro-O - [(formylmethyl) amino] cinnamonitrile diethyl acetal a

14) p-Trifluoromethyl-3-C (formylmethyl) amino] cinnamonitrile diethyl acetal.

β-cyanstyrenes, also referred to as cinnaaonitrile dialkylacetals, may be prepared by reacting substituted or unsubstituted benzoyl acetonitrile with 2,2-dialkoxyethylamine of 1 to 4 carbon atoms in each alkoxy moiety, in the presence of an aromatic solvent, resulting in α- (2, 2-dialkoxyethylamino) -β-cyano-substyrene having 1 to 4 carbon atoms in each alkoxy moiety which can be converted by reaction with trifluoroacetic acid to 2-substituted-phenylpyrrole-3-carbonitrile. Chlorination of the cyanophenylpyrrole thus formed with sodium hypochlorite or sulfuryl chloride in an inert solvent affords insecticidally, acericidally and nematocidally active 4,5-dichloro-2-substituted phenylpyrrole-3-carbonitrile. Conversion to the intermediate pyrrole can also be accomplished by treatment with concentrated hydrochloric acid at a temperature of between about 20 and 40 ° C. These reactions can be described by the following reaction scheme.

+ H ₂ NCH ₂ CH (OC ₂ H ₅ ) ₂ CN

CF ₃ CO ₂ H or

I HCl

'IN

NaOCl or ₂ or ₂ or ₂

KOC (CH3) ₃

In this reaction scheme, A represents a hydrogen atom, a C 1 -C 4 alkyl group optionally substituted by one C 1 -C 4 alkoxy group, one C 1 -C 4 alkylthio group, one to three halogen atoms, or a phenyl group optionally substituted by one or two C 1 -C 4 alkyl groups, C 1 -C 4 alkoxy or halogen atoms, a C 3 -C 4 alkenyl group optionally substituted by 1 to 3 halogen atoms, or a C 3 -C 4 alkynyl group ,

X is chlorine or bromine, R8 is C1 -C4 alkyl and L, R and M are as defined above.

Certain novel arylpyrrole compounds of formula I wherein A is hydrogen,

W is cyano and X, Y, L, M and R are as defined above, may be prepared by reaction

N-formyl-DL-phenylglycine or substituted

N-formylphenylglycine of formula VIII!

M

NHCH = O

R

CO _n H (VIII) in which hydrogen, fluorine, chlorine or bromine are each independently hydrogen, C 1 -C 3 alkyl, C 1 -C 3 alkoxy, C 1 -C 3 alkylthio carbon atoms, (C 1 -C 3) alkylsulfinyl, (C 1 -C 3) alkylsulfonyl, cyano, fluorine, chlorine, bromine or iodine, nitro, trifluoromethyl, the radical of formula R 1 CF 2, R 2 CO or NR 1 R 3. , or M and R, attached at adjacent positions together with the carbon atoms to which they are attached, may form a ring in which MR represents a residue

R.

iC

R 1 is S (O) _n or oxygen, represents a hydrogen atom, a fluorine atom, a difluoromethyl group, a fluorochloromethyl group or a trifluoromethyl group, an alkyl group having 1 to 3 carbon atoms, an alkoxy group having 1 to 3 carbon atoms represents a hydrogen atom or a (C1-C3) alkyl group, represents a hydrogen atom, a (C1-C3) alkyl group or the radical R (2) CO, represents a hydrogen atom or a (C1-C3) alkyl group and is a number of values ? 0, 1 or 2, with at least an equivalent amount of 2-chloroacrylonitrile and 2 to 3 equivalents of acetic anhydride. The reaction is carried out at an elevated temperature, preferably at an ambient temperature. from about 70 to 100 ° C.

The above reaction by reaction scheme.

can be described as follows

The thus prepared 2-phenylpyrrole-3-carbonitrile or 2-subst, phenylpyrrole-3-carbonitrile is readily converted to the corresponding 4-halogen-, 5-halogen- or

4,5-dihalo-2-substituted-phenylpyrrole-3-carbonitrile of formula II by reaction with at least 1 or 2 equivalents of sulfuryl halide, bromine or chlorine in the presence of a solvent such as dioxane, tetrahydrofuran, acetic acid or a chlorinated hydrocarbon solvent.

The preparation of monohalogenated pyrrole-3-carbonitrile requires the use of about 1 equivalent of halogenating agent, while 2 to 3 equivalents of this halogenating agent are required to prepare dihalopyrrole-3-carbonitrile. When sulfuryl chloride or sulfuryl bromide is used for this purpose, the reaction is generally carried out at a temperature below about 40 ° C, preferably between about 0 and 30 ° C, and elemental bromine is usually carried out at a temperature of about 30 to 40 ° C. Other halogenating agents which may be used include sodium hypochlorite, tert-butyl hypochlorite, N-bromosuccinimide, N-iodosuccinimide, and the like. The reaction may be described by the following reaction scheme.

(ID

The carbonitriles of formula (II) of the invention may also be prepared by reacting a substituted or unsubstituted benzoylacetonitrile with a C 1 -C 4 -dialkoxyethylamine in each alkoxy group, in the presence of an aromatic solvent, resulting in the formation of .alpha .- (2,2-dialkoxyethylamino) - C 1 -C 4 -cyanosubstituted styrene in each alkoxy group, which is then converted to 2-substituted phenylpyrrole-3-carbonitrile by treatment with trifluoroacetic acid or concentrated hydrochloric acid at a temperature between about 20 ° C and 40 ° C. of formula II. This reaction may be described by the following reaction scheme, wherein R 8 is C 1 -C 4 alkyl and L, R and M are as defined above.

^ C0 _of GF H or ^J

HCl

In accordance with the invention, the 3-nitro-2-phenylpyrrole and 3-nitro-2-subst, phenylpyrrole compounds of formula II can also be prepared by reacting α-nitroacetophenone or substituted α-nitroacetophenone with 2,2-dialkoxyethylamine containing 1 to 1 alkoxy in each alkoxy moiety. 4 carbon atoms. The reaction is generally carried out in the presence of an inert organic solvent, preferably an aromatic solvent, at elevated temperature to form α- (2,2-dialkoxyethylamino) -3-nitrostyrene or substituted α- (2,2-dialkoxyethylamino) -3-nitrostyrene, wherein each alkoxy moiety contains 1 to 4 carbon atoms, which is then converted to the 3-nitro-2-phenylpyrrole or 3-nitro-2-substituted phenylpyrrole of formula II by treatment with a mineral acid such as hydrochloric or hydrobromic acid. Reaction of the nitrophenylpyrrole thus prepared with sodium hypochlorite in the presence of an inert organic solvent at reduced temperature affords 2,3-dichloro-4-nitro-5-phenyl- or -5-substituted-phenylpyrrole of formula II.

The above reaction can be described by the following reaction scheme.

M

R

HCl cf ₃ every ₂ h or

NaOCl

Surprisingly, it has now been found that in addition to several methods described in the literature for the preparation of substituted and unsubstituted benzoylacetonitriles, these compounds can also be prepared by reacting an appropriately substituted benzoyl halide with an alkali metal hydride and an alkyl cyanoacetate such as tert-butyl cyanoacetate to Butyl (benzoyl or substituted benzoyl cyanoacetate) can be described by the following reaction scheme.

The cyanoacetic acid ester thus formed can then be converted to substituted or unsubstituted benzoylacetonitrile by heating in toluene containing p-toluenesulfonic acid (PTSA). This reaction may be described by the following reaction scheme.

Examples of tert-butyl (benzoyl and subst. Benzoyl) cyanoacetates used in the above reactions and examples of the resulting benzoylacetonitriles are shown in the following tables.

Tert-Butyl (benzoyl and substenzoyl) cyanoacetates

melting point (° C)

L M R

H 3-C1 4-C1 91 - 94 H H 4-0CF ₃ 81 - 84 H H 4-3r 113 - 115 H H 4-CF ₃ 146 - 147 H H 4-F 98 - 100 H H 4-CN 127 - 128 H H 4-CF ₃ CH ₂ O 136 - 139 H H 4-CH ₃ SO ₂ 127 - 129 H 3-F 4-F 91 - 94 H H 4-CH ₃ S 117 - 119 H H 4-CHF ₂ CF ₂ O 92 - 94 3-C1 5-C1 4-CH.O - —-

- 50 Benzoylacetonitrile

L M R melting point H H 4-C1 128.5-129.5 H 3-C1 4-C1 105-107 H H 2-C 153-155 H H 4-0C? ₃ 79-81 H H 4-CF-j 44 - 45 H 2-C1 4-C1 66 - 67 H H 3-C1 80-83 H H 4-CN 126-123 H H 4-F 78 - 80 H H 4-SO ₂ CH ₃ 129-132 H 3-F 4-F 74-75 H H 3-CF ₃ 58 - 60 H H _4-CH3 103.5-106 H H 4-NO ₂ 119-124 3-C1 5-C1 4-0CH ₃ -

N-substituted arylpyrroles of formula I may be prepared by reacting an appropriately substituted arylpyrrole of formula I wherein A is hydrogen and L, M, R, W, X and Y are as defined above with an appropriate alkylating agent and a suitable base. , for example, a C 1 -C 4 -based alkanol and a potassium tert-butoxide. This reaction yields an arylpyrrole bearing the same substituents as the starting material but, in addition to them, a C 1 -C 4 hydroxyalkyl group on nitrogen. Instead of C 1 -C 4 bromoalkanol, cyanogen bromide can be used in this reaction to provide the corresponding arylpyrrole of formula (I) substituted with cyano on nitrogen.

These reactions can be described by the following reaction scheme in which BrAlkOH is C 1 -C 4 bromoalkanol, K ^{+ O} -Bu is potassium tert-butoxide, L, M, R, W, X and Y are as defined in formula I and A is 1) a C 1 -C 4 hydroxyalkyl or 2) cyano group.

2-Phenylpyrrole-3,4-dicarbonitrile, 2-bromo-5-phenylpyrrole-3,4-dicarbonitrile and their phenyl-substituted derivatives can be obtained by reacting fumaronitrile with bromine in the presence of a chlorinated hydrocarbon such as chloroform at elevated temperature and following reacting the resulting bromofumaronitrile with N- (trimethylsilyl) methyl-5-methylbenzene thioimidate or a substituted derivative thereof in the presence of hexamethylphosphoramide at elevated temperature to give 2-phenylpyrrole-3,4-dicarbonitrile.

Bromination of the 3,4-dicarbonitrile thus prepared affords 2-bromo-5-phenylpyrrole-3,4-dicarbonitrile or the corresponding phenyl-substituted derivative when appropriately substituted N- (trimethylsilyl) methyl-5- is used in the previous reaction. methylbenzenethioimidate. The above process can be described by the following reaction scheme.

In this reaction scheme, HMPA is hexamethynylphosphoramide and TMS is trimethylsilyl.

!

CN CN

NC (-HBr) NC Br

(-TMS, -HBr, -CH ₃ SH)

R

In the examples that illustrate the process of the invention, the above schemes are utilized and these examples provide guidance for the preparation of other compounds of the invention not specifically mentioned herein.

The arylpyrrolv of the invention effectively suppresses insects, mites and nematodes. Accordingly, the compounds can be used to protect growing or harvested crops from attack by the aforementioned pests.

To effectively protect the aforementioned crops from insect, mite and / or nematode attack, plants, harvested crops or land on which they are grown ₍ generally applied from about 10 to about 10,000 ppm, preferably from about 100 to 5,000 ppm of arylpyrrole of formula I (this term includes all isomeric arylpyrroles of formulas II, III, IV, V, VI and VII) dispersed in water or other cheap liquid carrier. racecourses before attack by various pests, such as caterpillars and others, for example olissus leucopterus.

The aryl aryl pyrrols of the formula I according to the invention also effectively kill insects, nematodes and mites when applied to the leaves of plants and / or to the soil or water in which the plants grow, at a dose ranging from about 0.125 kg of active substance per hectare to 4; 0 kg of active per hectare látk3 ^r. Of course, higher application rates of arylproproles of formula (I) may also be used to protect crops from insect, nematode and mite attack, but these higher rates are generally unnecessary and harmful to the environment.

Although the arylpyrroles of the invention are effective in controlling insects, nematodes and mites themselves, they can be used in combination with other chemicals including other insecticides, nematocides and acaricides. For example, the arylpyrrols of the invention can be effectively used in conjunction with or in combination with phosphates, caroamates, pyrethroids, formamidines, chlorinated hydrocarbons, halobenzoylureas and the like.

The 2-aryl-3-cyano-4,5-dihalopyrroles prepared from the 3-cyanstyrene compounds of the invention are effective in controlling insects, mites and nematodes and can also be used to protect growing and harvested crops from attack by the above pests.

In practice, about 10 to about 10,000 ppm, preferably about 10,000 ppm, is generally applied to plants, to harvested crops or to the soil on which the crops are attacked by insects, mites and / or nematodes. from 100 to 5,000 ppm of halogenated arylpyrrole dispersed in water or other cheap liquid carrier.

The aforementioned halogenated arylpyrroles also effectively kill insects, nematodes and mites when applied to the leaves of plants and / or to the soil or water where plants are grown, at a dose ranging from about 0.125 kg active ingredient per hectare to 4.0 kg active ingredient per hectare. Obviously, higher application rates of halogenated arylpyrrole may also be used to protect crops from insect, nematode and mite attack, but these higher doses are generally unnecessary and harmful to the environment.

The aforementioned arylpyrroles are preferably formulated into dry compact granules, suspension concentrates, granular formulations, wettable powders, emulsifiable concentrates, powders, powder concentrates, microemulsions and the like, all of which can be used to protect plants by application to soil, water or / a on plant leaves. These compositions contain the compounds of the invention in admixture with inert, pharmacologically acceptable solid or liquid diluents.

For example, wettable powders, dusts and powder concentrates of the present invention can be prepared by co-grinding about 3 to 20% by weight of the arylpyrrols of Formula I with about 3 to 20% by weight of the anionic surfactant. One suitable anionic type surfactant is sodium sulfosuccinic acid dioctyl ester, in particular the OTB aerosol surfactant (American Cyanamid Company). These compositions also contain about 60 to 94% by weight of an inert solid diluent such as montmorillonite, attapulgite, chalk, talc, kaolin, diatomaceous earth, limestone, some of the silicates and the like.

Compressed granules which are particularly suitable for application to soil or water can be milled to roughly equal parts, usually about 3 to 20 parts, arylpyrroles and solid surfactant with about 60 to 94 parts gypsum. Mixture

59 is then compressed into small granules, about 24/48 mesh or larger.

Other suitable solid surfactants used in the manufacture of the above compositions are also nonionic block copolymers of ethylene oxide and propylene oxide. These block copolymers are commercially available from BASF Wyandotte Corporation under the name Pluronic 10R8, 17R8, 25R8, F38, F68, F77 or F87. These copolymers are particularly suitable for preparing compressed granules.

In addition to powders and the above-mentioned concentrated preparations, wettable powders and water-dispersible suspension concentrates may also be used.

These suspension concentrates are preferably applied to the leaves of the protected plants as aqueous preparations by spraying. These sprays can also be applied to the locus of the control of insect and mite pests or to the source of their food.

When the arylpyrrole-containing solid compositions of the invention are used for combination treatment with other pesticidal agents, such compositions may be applied sequentially or a composition comprising a mixture of the two components may be applied.

Similarly, the arylpyrrole-containing liquid compositions of the present invention may be mixed with compositions containing other pesticidal agents just prior to application (tankmix), or both may be applied sequentially separately, in the form of liquid sprays. The liquid spray formulations of the invention should contain about 0.001 to 0.1% by weight of the active arylpyrrole of the invention.

The invention is illustrated by the following non-limiting examples.

Intensity of signals in IR spectra are indicated by the following symbols:

w weak m medium with strong w wide belt

The shapes of signals in NMR spectra are denoted by common abbreviations.

Example 1

2-phenylpyrrole-3-carbonitrile

The following procedure is analogous to the method described in J. Org. Chem. 43, 4273-4276 (1978). 30.00 g of N-formylphenylglycine, together with 2-chloroacrylonitrile and acetic anhydride, are heated at 90 ° C for 1.5 hours. The clear reaction solution was concentrated in vacuo to yield

42.5 g of a brownish-orange semi-solid. The product was partially purified by silica gel chromatography. According to the proton N 3 / β spectra, this is a mixture of 73% 2-phenylpyrrole-3-carbonitrile and 27% 2-phenyl-3-cyano-5-methylpyrrole. After recrystallization from chloroform and recrystallization twice from 1,2-dichloroethane, 1.69 g of off-white solid was obtained, which was 96% of 2-phenylpyrrole-3-carbonitrile according to the proton Niv spectrum. The product melts at 148-152 ° C.

Microanalysis (molecular weight 168,19):

C, 78.55; H, 4.79; N, 16.66.

Found: C 78.52, H 4.73, N 16.54.

Example 2

4,5-dichloro-2-phenylpyrrole-3-carbonitrile and 5-chloro-2-phenylpyrrole-3-carbonitrile

- 63 To a solution of 2.00 g (11.9 mmol) of 2-phenyl-3-cyanopyrrole in 80 ml of methylene chloride are added dropwise, over 5 minutes using a syringe, 1.90 ml (3.19 g. (6 mmol) of surfuryl chloride. The temperature of the mixture is maintained between 5 and 10 ° C during the addition. Stirring at 5-10 ° C was continued for a further 90 minutes, after which the reaction mixture was vacuum filtered to recover 1.28 g of solid material at

192.5-195 ° C, identified as 5-chloro-2-phenylpyrrole-3-carbonitrile. The filtrate is diluted with 400 ml of ethyl acetate, washed twice with 200 ml of water, dried over sodium sulfate, clarified with charcoal, filtered after concentration in vacuo and the residue triturated with hexane. 0.60 g (yield 21.3%) of a pink-red solid is obtained, which, after recrystallization from 5 ml of hot acetone, yields 0.32 g (yield 9%) of 4,5-di-chloro-2-phenylpyrrole-3-carbonitrile. 254 DEG -255 DEG C. in the form of a orange-yellow brown solid.

IR (nujol suspension) V: 3165 (bs), 3120 (s),

2245 (3), 1570 (m), 1513 (m), 1440 (s),

1252 (m), 1069 (m), 996 (m, 920, m),

768 (s), 698 (3,665 (s) cm @ -1).

1 H-NMR (dimethylsulfoxide, ς values): 7.73 (d,

J = 6.6 Hz, 1.97H, 2 phenyl protons on C ₂ and C 8), 7.52 (t, J = 7.3 Hz, 2.04H, two phenyl protons on α, 7.44 (t, J = 7.3 Hz, 1.02H, one phenyl proton per).

C-NMR (dimethylsulfoxide, δ values): 137.51 (C _{2 of the} pyrrole carbon), 129.25 (C ₄ -phenyl carbon), 129.04 (C ₃ -phenyl carbons), 128.37 (C 4 -phenyl carbon) , 125.88 (C ₂ -C carbons, phenyl), 114.32 (BUC CG pyrrole carbon or carbon-nitrile), 114.14 (pyrrole carbon BUC carbon or nitrile groups), 110.72 (C-pyrrole carbon) 89.78 (C ₃ carbon pyrrole).

Microanalysis (molecular weight 237.09):

H, 2.55; N, 11.82; Cl, 29.91. Found: C 55.78, H 2.59, N 11.12, Cl 29.74.

- 65 Example 3 p-chloro-β-E (formylmethyl) amino] cinnamonitrile diethyl acetal

A solution of 250.00 g (1.39 mol) of p-chlorobenzoylacetonitrile and 203 ml (185.95 g of 1.39 mol)

2,2-diethoxyethylamine in 1300 ml of dry toluene was heated to reflux for 20 hours with a Dean-Stark sump to collect.

23.8 ml (95.2% of theory) of water. Hot turbid dark 1 *

The brown solution containing a large amount of undissolved solids is filtered through a pad of diatomaceous earth and, after dilution with 200 ml of ethyl acetate, is filtered through a silica gel column (7 cm x 13.5 cm). The filtrate was concentrated in vacuo to give 354.38 g (86.4% crude yield) of a clear dark oil which slowly solidified. After recrystallization from hot cyclohexane, the solid material gave 324.26 g (yield 79.1%) of an orange waxy solid. The NMP spectrum indicates that this product consists of 78% (Z) -isomer and 23% (E) -isomer of p-chloro-O - [(formylmethyl) amino] cinnamonitrile diethyl acetal. The product melts at 60-72 ° C. The following analytical data applies to another sample prepared in an analogous manner.

(nujol suspension) ffi £ 1600 _JX : 3325 (s), 3065 cm) 2197 (with), 1530 1314 (m), 1265 (m), 1173 (m), 1154 (m), 1128 (with), 1100 (with), 1060 (s), 1022 939 (m),

895 (m), 844 (s), 768 (m), 730 (m) cm-1

H-NMP (chloroform, values): 7.47 (d, J = 8.6 Hz, 2.12H, two aromatic protons). 7.37 (d,

J = 8.6 Hz, 2.12H, two aromatic protons), 5.10 (E) and 4.86 (Z) (bt, 1.25H, 1H, NH), 4.69 (Z) and 4, 60 (Ξ) (t, J = 5.1 Hz, 1, C5H, one methine proton and acetal carbon), 4.07 (E) and 4.05 (Z) (s, O, 33H, 3-enamine proton ), 3.71 (E) and 3.68 (Z) (q, J = 7.1 Hz,

2.22H, two methylene protons of one of the two ethoxy groups), 3.56 (Z) and 3.53 (E) (q, J = 7.1 Hz, 2.22H, two methylene protons of one of the two ethoxy groups), 3 18 (t, J = 5.1 Hz, 1.77H, two methylene protons of the ethylene acetal group), 1.20 (t, J = 7.1 Hz, 4.9OH, six methyl protons of one of the two ethoxy groups).

C-NMR (chloroform, A-values) · 161.21 (α-enamine carbon), 136.29 (Z) and 134.60 (E) (either a or G ^ carbon of the phenyl ring),

134.08 (Z) and 132.30 (E) (either 0 _χ or C ₄ carbon of the phenyl ring), 129.34 (Z) and 129.89 (E) (either C ₃ and C 8 or a phenyl ring), 128.94 (Z) and 128.63 (E) (either C ₃ and C 8 or a phenyl ring); 121.19 (Z) and 119.50 (S) (nitrile carbon »

groups), 99.43 (Z) and 100.63 (E) (O-enamine carbon), 61.88 (Z) and 63.25 (E) (methine carbon of the acetal residue),

62.64 Z) and 63.03 (E) (methylene carbons of ethoxy groups), 46.32 (Z) and 47.33 (E) (methylene carbon of ethylamino),

15.26 (methyl carbons of ethoxy).

- 68 Microanalysis (MW 294,78):

calculated 61.11% C, found 61.25% C,

H, 6.50; N, 9.51; Cl, 12.03; H, 6.25; N, 9.34; Cl, 12.35.

Example 4

2- (p-chlorophenyl) pyrrole-3-carbonitrile

(mol weight 202,64)

69. To 108 ml of trifluoroacetic acid, with stirring at 23 ° C, 54.00 g (0.183 Bol) of solid p-chloro-β-E (formylmethyl) amino] cinnamonitrile diethyl acetal are added over 45 minutes. This addition induces an exothermic reaction associated with a temperature rise to 38 ° C. After 32 minutes a solid product began to precipitate. After the addition was complete, the reaction mixture was stirred for 30 minutes, then filtered in vacuo and the solid material was washed first with trifluoroacetic acid, then with a mixture of ethyl acetate and hexane and finally with hexane. 16.83 g (45.4%) of an off-white solid, m.p. 165-166 ° C. The following analytical data was obtained for an analogously prepared sample.

IR (nujol suspension) s) _{> 8χ} : 3275 (Ss), 2225 (s),

1502 (s), 1410 (a), 1275 (a), 1200 (a),

1108 (·), 1023 (a), 999 (a), 908 (m)

843 (·), 752 (s), 722 (s), 695 (s), (620 (s)), and “ ¹ .

1 H-NMR (acetone, δ values): 11.22 (very broad s,

0.99 H, one proton in the N-H group of the pyrrole residue), 7.82 (d, J = 8.9 Hz, 2.46H, two aromatic phenyl protons), 7.51

M or / and R

4-C1

3.4-di-Cl

2- Cl 4 -OCF. ₃

2.4-di-Cl

3- C1

4- CN

4-F

4-SO ₂ CH ₃

3.4- di-F

3- CF ₃

4- COOCH ₃ 4-CH ₃ 4-NO ₂ melting point> ..... CcL ".......

165-166

216-221

156-157

143-145

179-180

197-199

150-156

210-212

167-170

221-221.5

173 - 175.5

166-168

155.5 - 158 117 - 137

174-177 used acid conc. HC1, CF ₃ COOH, CF ₃ COOH, CF ₃ COOH, CF ₃ COOH

CF ₃ COOH

CF ₃ COOH

CF ₃ COOH

CF ₃ COOH conc. Cf ₃ cooh cf ₃ cooh cf ₃ cooh cf ₃ cooh

CF ₃ COOH

CF ₃ COOH

The solids were washed first with acetic acid and then with water and recrystallized from hot ethyl acetate. The resulting product melts at 259-261 ° C. Additional samples of this product were prepared by similar procedures. Analytical data for one of these products is given below.

IR (nujol suspension) 3170 (Ss), 3100 (m),

2225 (s), 1509 (m), 1097 (m), 825 (s),

717 (m), 660 (m) cm -1.

H-HMR (dimethylsulfoxide, f (f) values: 7.72 (d, J = 8.6 Hz, 2.00H, two aromatic protons),

7.56 (d, J = 8.6 Hz, 2.00H, two aromatic protons).

C-NMR (dimethylsulfoxide, cT values): 136.01 (C8 carbon of pyrrole), 133.92 (C ^ carbon of p-chlorophenyl), 129.09 (C ^ and carbons of p-chlorophenyl),

127.41 (C ₄ carbon p-chlorophenyl), 127.11 (C 4 carbon p-chlorophenyl), 114.49 (carbon nitrile group), 114.10 (C 3 carbon pyrrole), 110.92 (C 4 carbon pyrrole) )

90.09 (C ^-pyrrole carbon).

- 74 Microanalysis (MW 271,54):

calculated found

C 48.65, C 49.22,

H 1.86, H 2.12,

N 10.39, N 9.85,

39.17% Cl; 39.03% Cl.

Example 6

4,5-dibromo-2- (α, α, ω-trifluoro-p-tolyl) pyrrole-3-carbo nitrile

To a stirred mixture of 0.8 g of 2- (α, α, α-trifluoro-p-tolyl) pyrrole-3-carbonitrile in 70 mL of chloroform was added 2 mL of bromine. The mixture was stirred overnight to give a white solid which was filtered off. According to thin layer chromatography (ethyl acetate-hexane 1; 1) the product is a single component. The above substance melts above 230 ° C.

Analysis; for C 36.55%, H 1.27, N 7.11, Br 40.61; Found: C, 36.40, H, 1.08, N, 6.99, Br.

Using the procedures described in Examples 5 and 6, the following compounds were prepared by substituting 2- (β, α, α-trifluoro-p-tolyl) pyrrole-3-carbonitrile with an appropriately substituted phenylpyrrole-3-carbonitrile;

L Μ R X Y temperature melting (° « Η Η 4-Ν0 ₂ Br Br 274-277 Η Η 4-F Cl Cl > 220 Η Η 4-F Br Br > 220 Η Η 4-SO ₂ CH ₃ Cl Cl > 230 Η 3-F 4-F Cl Cl > 230 Η 3-F 4-F Br Br ? 220 2-C1 3-C1 4-C1 Cl Cl 2-Br 3-Βγ 4-Br Br Br Η Η 4-OCF ₃ Cl Cl 222-225 Η Η 4-OCF ₃ Br Br 231-232 Η Η 4-0CF-, Cl H

L Μ R X Ϊ temperature melting point (° C) Η 4-CN Br Br > 230 Η 4-CN Cl Cl > 240 Η Η 4-SO ₂ CH ₃ Br Br > 230 Η Η 4-Ν0 ₂ Cl Cl 246-249 Η 3-C1 4-C1 Br Br > 260 Η Η 3-C? ₃ Cl Cl > 230 Η Η 4-COCH ₃ Cl Cl 251-254 Η 2,3-CH = CH- Cl Cl 244-247 Η Η 4-CH ₃ Cl Cl 215-217 Η 2-C1 4-C1 Br Br > 230 Η H 3 -C 1 Cl Cl > 230 Η 2-C1 4-C1 Cl Cl > 230 Η H 4 -C 1 Br Br 273-274 Η H 2 -C 1 Br Br > 230 Η H, 4-CT Cl Cl > 230 Η H 4-Br Cl Cl 235 Η H 2 -C 1 Cl Cl 7 230

L Μ R X Y temperature melting point (° C) Η 3-C1 4-C1 Cl Cl > 235 Η Η Η Cl Cl 254-255 Η Η 4-C1 Cl Cl 255-257 Η Η 4-CF 3 Br Br > 230 Η Η 4-C1 Cl Br 262-263 (decomposition) Η Η 4-G1 Br Cl 250-258 (decomposition) Η 3-C1 5-C1 Cl Cl > 230 Η 3-C1 4-C1 Cl Br ? 230 2-C1 4-C1 5-F Cl Cl 207-210

79 Example 7

3-nitro-2-phenylpyrrole

+ H ₂ NCH ₂ CH (OEt) ₂

5.7 g (0.0345 mol) of α-nitroacetophenone are dissolved in 100 ml of toluene and added to the solution.

4.6 g (0.0345 mol) of aminoacetaldehyde diethyl acetal. The reagents were placed in a 4 L round bottom flask equipped with a Dean-Stark well. The well is filled with molecular sieves (4 x 10 ^-10 m) and the mixture is heated under reflux for 18 hours. Evaporation of toluene in vacuo yielded 8.36 g of brown oily α- (2,2-diethoxyethylamino) -β-nitrostyrene.

To this oily material was added 50 ml of concentrated hydrochloric acid and the flask was circulated to turn the oily material to a yellow suspension.

After 10 minutes, the solid product was filtered off. 2.48 g of a yellow solid are obtained, which, after recrystallization from a mixture of ether, ethyl acetate and hexane, yields 2.08 g (31%) of the product in two fractions, m.p. 190-192 ° C.

IR: 1485 cm ^-1 (H ₂ O).

1 H-NMR (CDCl 3): 6.73 (m, 2H), 7.46 (m, 5H).

Example 8

2,3-dichloro-4-nitro-5-phenylpyrrole

To a mixture of 1.56 g (0.0083 mol) of 3-nitro-2-phenylpyrrole in 60 ml of dioxane is added dropwise 25.9 g (0.0182 mol) of commercial sodium hypochlorite while cooling in ice. then acidified with concentrated hydrochloric acid and water and diethyl ether were added. The layers were separated, the upper organic layer was washed with water and, after drying over anhydrous magnesium sulfate, concentrated in vacuo. 2.21 g of a yellow solid are obtained, which is purified by chromatography on silica gel using a gradient elution of ethyl acetate / hexane mixtures containing an increasing proportion of ethyl acetate. After evaporation of the appropriate fractions, 0.77 g (36%) of a yellow solid is obtained. 190.5 ° C.

Analysis: for ^C io ^H 6 ^N 2 ° 2 ^C1 2 requires 46.72% C, 2.35% H, 10.90% N;

Found: C, 46.96; H, 2.86;

The procedures of Examples 7 and 8, respectively, using the appropriately substituted α-nitroacetophenone and 2,2-dialkoxyethylamine, wherein each alkoxy moiety contains 1 to 4 carbon atoms, yield the corresponding substituted α- (2,2-dialkoxyethylamino) -β- nitrostyrene, which is converted to 3-nitro-2-substituted phenylpyrrole by treatment with hydrochloric acid, hydrobromic acid or trifluoroacetic acid. Reaction of this substituted phenylpyrrole with sodium hypochlorite in dioxane gives the corresponding chloro analogues, while reaction of this substituted phenylpyrrole with bromine in chloroform gives the corresponding bromo analogues. The products are summarized in the following overview.

L Μ R X Y temperature (° C) thaw Η Η Η Cl Cl 190-190, 5 Η 4-C1 Η Cl Cl 214-215 - Η 4-C1 Η Br Br 203-204 (decomposition) Η Η Η Br Br 148.5-149 3-C1 4-C1 C Cl Cl 219-220 (decomposition) Η 4-Br Η Cl Cl 222-223 (decomposition) Η Η 4-CF, Cl Cl 166-168

Example 9

4,5-dichloro-2- (3,4-dichlorophenyl) -1-methylpyrrole-3-carbonitrile

In a 100 ml flask, 2 g of 4,5-dichloro-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile was dissolved in 60 ml of dry tetrahydrofuran to give a dry brown solution, to which 1 equivalent of tert. of potassium butoxide. After a few minutes, the mixture changes to a Sulfur solution, to which 1 equivalent of methyl iodide is added via syringe. The reaction mixture was heated at reflux for 4 hours, then stirred at room temperature overnight. The following day, 50 ml of water was added and the resulting mixture was extracted four times with 50 ml of chloroform each. The organic phases are combined and, after drying over magnesium sulphate, concentrated. The white solid was purified by flash chromatography on silica gel, eluting with ethyl acetate / hexane (1.80 g, 86% yield) as a white solid, mp 154-156 ° C.

As described above, the following compounds are obtained by substituting 4,5-dichloro-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile with appropriately substituted phenylpyrrole-3-carbonitriles or 3-nitro-2-substituted phenylpyrroles.

AND L M R X Y melting point (° C) ch ₃ H H 4-C1 Cl Cl 152-153 CgHjOCHg H 3-C1 4-C1 Cl Cl 128-130 H 3-C1 4-C1 Cl Cl 137-138 OH ₃ H 3-C1 4-C1 Cl Cl 154-156 CH ₃ H H 4-CF ₃ Br Br 145-146 Cgi ^ -CÍL, H H 4-CF ₃ Br Br 145-147 C 8 H -cHa H 3-C1 4-C1 Cl Cl 95 - 96 CH 2 CH-CH 2 H 3-C1 4-C1 Cl Cl 69-70 CH _O "C = CH Cl _O r H 3-C1 4-C1 Cl Cl CH = C-CH ₂ H 3-C1 4-C1 Cl Cl 147-148 CH ₃ SCH ₂ 5 3-C1 4-C1 Cl Cl

AND L M R X Ϊ melting point (° 0) C (CH3) ₃ H H 4-CF ₃ Cl Cl ch ₃ H H 4-CT ₃ Cl Cl 99-100 C18H22N2O4S H 3-C1 4-C1 Cl Cl 74-75 0 C 6 -C 8 -C 6 H 3-Cl 4-C1 Cl Cl 118-120 c ₂ h ₅ -och ₂ H H 4-CF ₃ Cl Cl 99-100 ch ₃ H H 4-OCH ₃ Br Br 112-115 ch ₃ H H 4-C1 Br Br 197 - 201 C 2 ^ 0 (^ 2 H H 4-OCFj Cl Cl 46 - 47 CH ₃ H H 4-OCF ₃ Cl Cl 72-73 C ₆ ^h 5 ^-CH 2 H H 4-OCF ₃ Cl Cl oil c ^ oc ^ H H 4-C1 Cl Cl - HOCH ₂ CH ₂ H 3-C1 4-C1 Cl Cl 143-145 NC H 3-C1 4-C1 Cl Cl 251-252 C ₆ H ₅ CH ₂ OCH ₂ H 3-C1 4-C1 Cl Cl 88-89 Cl-CH ₂ 0 H 3-Cl 4-C1 Cl Cl 118-120 ic »c-ch ₂ H 3-C1 4-C1 Cl Cl 115-116 CH-J H H 4-C1 Br CF ₃ 126-139

AND L M R X Y melting point (° C) CgHjOCHg H H 4-C1 Br cf ₃ 91-92 CgHj-OCHg H 3-C1 4-C1 Cl Cl 118-120 C ₂ H ₅ -OCH ₂ H H 4-C1 Br Br 104-105 C ^-CHg H H 4-C1 Br Br 81-82 CH ₃ H H 4-Cl Br Br 197 - 201 CN H H 4-C? ₃ Cl Cl 138-139 CgHj-OCHg H H 4-CF ₃ Br cf ₃ 104-105 CgHj-OCHg H H 4-C? ₃ H cf ₃ 76 - 77 CgHjOCHg H 3-C1 4-C1 Br cf ₃ 80-81

Example 10 1-Benzyl-4,5-dibromo-2- (α, α, α-trifluoro-p-tolyl) pyrrole -3-carbonitrile

Mix 1.5 g in a 100 ml flask

4,5-dibromo-2- (α, α, α-trifluoro-p-tolyl) pyrrole-3-carbonitrile with 50 ml of dry tetrahydrofuran and 1 equivalent of potassium tert-butoxide was added with stirring to the resulting clear dark solution. After a few minutes, the resulting solution became clear and then 0.65 g of benzyl bromide was added via syringe. The reaction mixture was heated at reflux overnight and the following day a sample was taken and subjected to thin layer chromatography (a mixture of equal parts of ethyl acetate and hexane to indicate the presence of both starting material and product). Add 50 ml

90 water and the resulting mixture is extracted four times with 50 ml of chloroform each. The organic phases were combined, washed four times with 50 ml of 10% aqueous sodium hydroxide solution each time, the organic layer was dried over magnesium sulfate and evaporated. The brown solid residue crystallized from ethyl acetate / hexane to give 0.75 g (40.7%) of the desired product melting at 145-147 ° C with decomposition.

Example 11

4,5-dichloro-2- (3,4-dichlorophenyl) -1- (ethoxymethyl) pyrrole-3-carbonitrile

- 91 1,0 & (0,003 mol) 4,5-dichloro-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile are dissolved in 10 ml of dry tetrahydrofuran and 0.37 g (0, Potassium tert-butoxide and then 0.312 g (0.0033 mol) of chloromethyl ethyl ether. The resulting mixture was stirred at room temperature for about 1 hour and then poured into a large volume of water to precipitate the product. After collecting and drying the white solid, 1.0 g (91%) of the title compound of melting point 128-130 ° C is obtained.

Example 12

4-chloro-3-cyano-2- (p-chlorophenyl) pyrrole

+ 2 NaOCl - Cl dioxane

Cl

CN

Cl

CN \ / \ / c:

i — Cl

To a solution of 17.87 g (88.2 mmol; 1.00 equivalents) of 2- (p-chlorophenyl) -3-cyanopyrrole in 800 mL of dioxane was added dropwise 250.15 g over 30 minutes with magnetic stirring at 20 ° C. 5.25% (w / w) sodium hypochlorite (13.13 g;

176.4 mmol; 2.00 equivalents). The reaction mixture was stirred for 30 minutes at room temperature, then poured into 2200 ml of water, the resulting mixture was freed of a small amount of black solid by vacuum filtration and the filtrate acidified to pH 2 with concentrated hydrochloric acid. washed with water to give 22.41 g of a brown solid, which was treated with 100 mL of 5% aqueous sodium hydroxide to dissolve most of the material and to dissolve only a small amount of the black solid. This black material was dissolved in 100 ml of ethyl acetate, and the solution was washed with 75 ml each

93% 5% aqueous sodium hydroxide solution, water and saturated aqueous sodium chloride solution, the ethyl acetate layer is dried over magnesium sulphate, clarified with charcoal and filtered on a rotary evaporator under vacuum. 1.10 g (yield 5.3%) of an orange-brown solid are obtained, which, after recrystallization from a mixture of ethyl acetate and chloroform, yields 0.51 g (yield).

2.4%) Off-white solid 4-chloro-3-cyano-2- (p-chlorophenyl) pyrrole, m.p. 251-253.5 ° C.

Example 13

Preparation of 5-bromo-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile

2.0 g (0.008 mol) of 2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile are dissolved in 100 ml of dioxane under heating at 40 to 50 ° C, the resulting solution is cooled to 30 ° C and added to 1.3 g (0.008 mol) of bromine. After stirring at room temperature for 1 hour, the resulting solution was evaporated in vacuo to give 2.2 g (88%) of a gray colored solid melting at 233-236 ° C with decomposition.

5-Bromo-2- (3,4-dichloro-3-nitropyrrole) was prepared in an analogous manner using 2- (3,4-dichlorophenyl) -3-nitropyrrole as starting material.

- 95 Example 14

Preparation of 5-bromo-4-chloro-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile

0.158 g (0.005 mol) of 5-bromo-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile was dissolved in 5 ml of tetrahydrofuran, an equivalent amount of tert-butyl hypochlorite was added and the solution was stirred overnight.

The reaction solution is poured into water and the precipitate formed is collected. 0.052 g (30%) of the desired product melting above 275 ° C is obtained.

In an analogous manner, 2-bromo-3-chloro-5- (3,4-dichlorophenyl) -4-nitropyrrole can be prepared starting from 2-bromo-5- (3,4-dichlorophenyl) -4-nitropyrrole.

Example 15

Preparation of 5-bromo-4-chloro-2- (p-chlorophenyl) pyrrole-3-carbonitrile

97 To a solution of 4-chloro-2- (p-chlorophenyl) pyrrole-3-carbonitrile (0.17 g, 0.67 mmol; 1.00 equivalents) in chloroform (100 mL) at 22 ° C with magnetic stirrer. a solution of 0.20 mL (0.62 g; 3.88 mmol; 5.79 equivalents) of bromine in 5 mL of chloroform was added dropwise over 30 minutes. There is no exothermic reaction during the addition. The resulting mixture was stirred at room temperature for 3.25 hours, then the clear red reaction solution was evaporated in vacuo. 0.28 g of off-white solid material is obtained which, after stirring with a mixture of hexane and methylene chloride and subsequent vacuum filtration, yields 0.23 g of off-white fluffy solid which melts with decomposition at 262 to 263 ° C.

Example 16

Preparation of 5-chloro-4-bromo-2- (p-chlorophenyl) pyrrole-3 carbonitrile

Cl

To a solution of 1.00 g (4.22 mmol; 1.00 equivalents) of 5-chloro-2- (p-chlorophenyl) pyrrole-3-carbonitrile in 300 mL of chloroform was added dropwise at 45 ° C with magnetic stirring over 30 minutes. A solution of 0.40 mL (1.24 g; 7.76 mmol; 1.84 equivalents) of bromine in 25 mL of chloroform was added for 30 min. There is no exothermic reaction during the addition and a small amount of solid material precipitates at the end of the addition. The reaction mixture was quenched

The mixture was stirred at room temperature for 19.5 hours and then evaporated in vacuo to give 1.49 g of an off-white solid, which was stirred with a mixture of hexane and methylene chloride. After vacuum filtration, it is obtained

1.33 g (100% yield) of a fluffy white solid melting at 250-258 ° C with decomposition.

- 99 Example 17

Preparation of 5-chloro-2- (p-chlorophenyl) pyrrole-3-carbonitrile

To a solution of 2.40 g (11.8 euaol; 1.00 equivalents) of 2- (p-chlorophenyl) pyrrole-3-carbonitrile in 65 mL of glacial acetic acid at 35 ° C with magnetic stirring was added dropwise using a syringe. over 5 minutes 0.75 a1 (1.26 g;

9.34 mmol; 0.79 equivalents) of sulfuryl chloride. About 5 minutes after the addition was complete

100% of the solution precipitates solid material. The reaction mixture was stirred at room temperature for 45 minutes, then filtered and the solid product was washed thoroughly with cold acetic acid. 2.08 g (74% yield of crude product) of an off-white solid are obtained, which, after recrystallization from 75 ml of hot acetic acid, yields 1.63 g (yield 58%) of a 97% pure product, m.p. 261 ° C.

Example 18

Preparation of 2- (3,4-dichlorophenyl) -1-methylpyrrole-3-carbonitrile

CH ₃ I

Cl

101

In a 100 ml flask, 2.0 g of 2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile was dissolved in 50 ml of dry tetrahydrofuran and 1 equivalent of potassium tert-butoxide was added. To the resulting slightly cloudy solution was added by pipette 1 equivalent of methyl iodide, while the solution lightly lightened. The flask was fitted with a drying tube and the mixture was stirred at room temperature overnight.

The next morning, a light colored precipitate is present in the flask. Upon addition of 50 ml of water, a sulfur solution is formed first from which a solid precipitate is formed. This solid material was filtered off and compared to 8 starting materials by thin layer chromatography (25% ethyl acetate in hexane). The chromatogram shows one new spot progressing faster than the starting material. The product obtained above is dried overnight in a vacuum oven at 50 ° C to give 1.31 g (62% yield) of the title compound, m.p. 140-142 ° C.

102

Example 19

Preparation of 4,5-dichloro-2- (3,4-dichlorophenyl) -1-methylpyrrole-3-carbonitrile

In a 50 ml round-bottomed flask, 0.5 g of 2- (3,4-dichlorophenyl) -1-methylpyrrole-3-carbonitrile was mixed with 35 ml of glacial acetic acid. The mixture is gently warmed by an immersion cooker to dissolve all pyrrole.

103 equivalents of sulfuryl chloride were added via pipette to the resulting clear solution, and the resulting solution was stirred at room temperature for 12 hours.

After these 12 hours, the reaction solution is poured into 50 ml of water, the precipitated white precipitate is filtered off and dried in a vacuum oven at 50 ° C for 3 hours.

The solid material obtained is identical to that of Example 9 by thin layer chromatography (25% ethyl acetate in hexane) and IR. The yield of the product is 0.36 g (56%).

Example 20

Preparation of 4,5-dichloro-2- (3,4-dichlorophenyl) -1- (2-hydroxyethyl) pyrrole-2-carbonitrile

- 104

To a mixture of 2.0 g (6.5 mmol) of 4,5-dichloro-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile and 0.88 g (7.8 mmol) of potassium tert-butoxide in 50 ml. of dioxane, under stirring and reflux, was added 0.98 g (7.8 mmol) of bromoethane. The reaction mixture was stirred at reflux for 12 hours, cooled, diluted with 50 ml of water and extracted several times with chloroform. The combined chloroform extracts were dried over magnesium sulfate and concentrated in vacuo. The solid residue was dissolved in ethyl acetate with heating, and the solution was cooled, leaving the predominantly pyrrole starting material. The mother liquor was concentrated and the residue was recrystallized from 20% ethyl acetate in hexane. This gives 0.31 g of a white solid, m.p. 143-145 ° C.

- 105 Analysis: for = ₁₆ H ₂₃ N ° 4 calculated 44.57% 0.29 »H, found 44.77% C, 2.29% H,

N, 8.00; Cl, 40.57; 8.06% N, 40.14% Cl.

Example 21

Preparation of 4,5-dichloro-2- (3,4-dichlorophenyl) pyrrole-1,3-dicarbonitrile

To a solution of 1.52 g (5 mmol) of 3-cyano-4,5-dichloro-2- (3,4-dichlorophenyl) pyrrole in 20 mL of anhydrous tetrahydrofuran was added portionwise 617 mg (55 mmol) of potassium tert-butoxide. After 30 minutes, add

A solution of 583 mg (5.5 mmol) of cyanogen bromide in 1 mL of tetrahydrofuran and the reaction mixture was allowed to stand at room temperature overnight. The solvent was removed by rotary evaporation, the residue was stirred with water and extracted with ethyl acetate. The organic layer was washed with water and saturated sodium chloride solution, dried over magnesium sulfate, evaporated and the residue was crystallized from ethyl acetate.

1.07 g of white crystalline product is obtained, m.p. 250.5-252.0 ° C.

IR (Nujol): 2255, 2245 cm ^-1 (CN).

Mass spectrum: 331.9 (M + 1).

Analysis: for (330.99) calculated C 43.54, H 0.91, N 12.70, Cl 42.85; Found: C, 43.62; H, 0.93; N, 12.63; Cl, 41.95.

107 Example 22

Preparation of 4,5-dichloro-2- (3,4-dichlorophenyl) -1- (3-iodo-2-propynyl) pyrrole-3-carbonitrile

108 To a mixture of 4,5-dichloro-2- (3,4-dichlorophenyl) -1- (2-propynyl) pyrrole-3-carbonitrile (1.91 g, 5.5 mmol) and methanol (500 ml) was added first with stirring 69 ml of 10% aqueous sodium hydroxide and then 0.70 g (2.7 mmol) of iodine. The reaction mixture was stirred for 12 hours, then acidified and diluted with 200 mL of water. The precipitated solid was filtered off and recrystallized from methanol. 0.51 g of white crystalline product is obtained, m.p. 115-116 ° C.

This reaction can also be used to convert any of the substituted N-alkynyl arylpyrroles of formula III, IV, V, VI or VII of the invention to the corresponding N-substituted-3-iodo-2-propynyrylpyrrole of the invention.

Example 23

Preparation of 2- (3,4-dichlorophenyl) -4,5-diiodopyrrole-3-carbonitrile

- 109 -

To a solution of 3.0 g (0.0127 mol) of 2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile in 100 ml of tetrahydrofuran was slowly added 5.7 g (0.0254 mol) of N-iodosucciniaid. The reaction mixture was stirred at 25 ° C for several hours until a thin layer chromatography of the reaction mixture (silica gel; ether-petroleum ether-acetic acid 100: 100: 1) indicated complete reaction. The resulting mixture was evaporated in vacuo to a residue containing pyrrole and succinimide. The crude solid was dissolved in 500 ml of ether and shaken five times with 400 ml of water each time to remove the succinimide. Etherová

The 110 phase was dried over sodium sulfate and evaporated in vacuo. 2.0 g (32.3%) of a gray-brown solid are obtained, which, when heated, emits red vapors and melts above 230 ° C.

Example 24

Preparation of 2-phenyl-1-pyrroline-4-carbonitrile

CN

mol% nBu ₄ N ⁺ F

THF (16 h) room temperature

NC

A solution of 0.65 ml (0.01 mol) acrylonitrile and 2.4 g (0.01 mol) N- (trimethylsilylmethyl-S-methylbenzenethioimidate) in 100 ml tetrahydrofuran was cooled to -5 ° C in an ice / acetone cooling bath. and in a nitrogen atmosphere to it during

A solution of 1.0 ml of a 1N tetrabutylammonium fluoride solution in 20 ml of tetrahydrofuran is added dropwise over 111 minutes. The resulting solution was stirred at -5 ° C for 30 minutes, then allowed to slowly cool to room temperature, stirred for an additional 18 hours, then the solvent was evaporated under reduced pressure. The residue was partitioned between ether and water and the aqueous layer was extracted with fresh ether. The combined organic phases are washed with water and then with a saturated sodium chloride solution, dried over magnesium sulphate and, after filtration, the filtrate is cooled to give 1.2 g (70% of theory) of an off-white solid having the same spectral data as the material described by Tsuge [J. Org. Chem. 52, 2523 (1987)].

Analysis: Calculated: C, 77.65; H, 5.88; H, 16.47;

Found: C 77.55, H 5.83, N 16.39.

The product melts at 95-97 ° C.

112

Example 25

Preparation of 2-phenylpyrrole-4-carbonitrile

In nitrogen atmosphere, 0.23 g (0.001 mol) of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone and 0.17 g (0.001 mol) of 2-phenyl are dissolved in 13 ml of 1,2-dimethoxyethane. of 1-pyrroline-4-carbonitrile to a clear orange solution, to which 0.08 ml (0.001 mol) of pyridine is added in a single portion, with a slight exothermic reaction (temperature rise to about 28 ° C) and immediate precipitation of a green-brown precipitate . The resulting suspension

113 was stirred at room temperature for 18 hours, during which time most of the solvent was evaporated.

The brownish semisolid residue was partitioned between ether and dilute sodium carbonate solution, the red-brown aqueous layer was extracted twice with ether, the combined ether phases were washed with water and saturated sodium chloride solution, dried over magnesium sulfate and the solvent was evaporated under reduced pressure. A white semi-solid residue is obtained which, after recrystallization from ethylene dichloride and decolourising with charcoal, gives 0.1 g of lavender colored crystals.

The same product is obtained directly in a single step by condensation of α-chloroacrylonitrile with N- (trimethylsilylmethyl-S-methylbenzenethioimidate) using tetrabutylammonium fluoride as a catalyst (a procedure analogous to the preparation of 2-phenyl-1-pyrroline-4-carbonitrile described above).

Analysis: Calculated: C, 78.57; H, 4.76; N, 16.67.

Found: C, 78.65; H, 4.70; N, 16.43.

The product melts at 155-158 ° C.

- 114

Example 26

Preparation of 2,4-dibromo-5-phenylpyrrole-3-carbonitrile

To a stirred solution of 0.84 g (0.05 mol) of 2-phenylpyrrole-4-carbonitrile in 20 ml of chloroform was added dropwise a solution of 0.6 ml (0.012 mol) of bromine in 5 ml of chloroform over 20 minutes under nitrogen. The resulting solution was stirred at room temperature for 18 hours, then the solvent was evaporated under reduced pressure. The solid residue yielded 0.6 g of the desired final product after recrystallization from dichloroethane (activated carbon clarification), melting at 239-242 ° C.

- 115 Analysis: ^C n ^H 6 ^Br 2 ^N 2 requires 40.49% C, 1.84% H, 49.08% 'Br 8.59% * Nj Found 39.88% C, 1.87% H, 48.81% Br, 8.48% N.

2,4-Dibromo-5- (p-chlorophenyl) pyrrole-3-carbonitrile, melting at 270-272 ° C, was also prepared as described in Examples 24, 25 and 26.

Example 27

3 ', 4'-dichloro-3- (1,3-dioxolan-2-yl) propiophenone

- 116 To a vigorously stirred mixture of magnesium shavings 0,64 g (26 mmol) and 10 ml tetrahydrofuran, presented in a 100 ml three-necked round-bottomed flask equipped with a thermometer, a 60 ml dropping funnel and a nitrogen purge, 4.7 g (26 mmol) of 2- (2-bromoethyl) -1,3-dioxolane in 40 ml of tetrahydrofuran are added dropwise at 25 ° C. The rate of addition was controlled to maintain the temperature of the mixture below 50 ° C.

The reaction mixture was then stirred at 25 ° C for 1 hour.

120 ml of tetrahydrofuran are mixed with 5.0 g (22 mmol) of potassium 3,4-dichlorobenzoate under a nitrogen atmosphere. The Grignard solution prepared above is rapidly decanted from unreacted magnesium shavings and added dropwise to the potassium-3,4- suspension with rapid stirring. dichlorobenzoate. The mixture was stirred at 25 ° C for 24 h before 50 mL of diethyl ether was added. and 15 µl of 3N hydrochloric acid and the layers were separated. The organic layer was washed with saturated aqueous sodium bicarbonate until neutral, then washed once more with 10 ml of sodium chloride solution, dried over sodium sulfate and evaporated on a rotary evaporator. The residue was chromatographed on silica gel using hexane / ethyl acetate (3: 1) as eluent.

117 gave 4.3 g (60%) of the desired ketoacetal as a white solid, mp 115-117 ° C.

Example 28

Preparation of 3- (3,4-dichlorobenzoyl) propionaldehyde

To 30 ml of a 0.2 M oxalic acid solution (prepared by dissolving 0.9 g of oxalic acid dihydrate in 30 ml of water) and 5 ml of ethanol is added 10 g (26 mmol) of 3 ', 4'-dichloro-3- (1,3 (dioxolan-2-yl) propiophenone. The reaction mixture was heated to reflux for 1 hour, then allowed to cool, most of the ethanol was evaporated on a rotary evaporator and 100 ml of diethyl ether together with 20 ml were added to the residue.

118 saturated aqueous sodium bicarbonate solution. The layers were separated, the organic phase was dried over magnesium sulfate and evaporated on a rotary evaporator.

A viscous yellow oily residue is obtained which is chromatographed on silica gel with hexane / ethyl acetate (3: 1) as eluent.

6.3 g (75%) of the desired ketoaldehyde as a white solid.

Example 29

Preparation of 2- (3,4-dichlorophenyl) pyrrole

119 To a suspension of 6 g (26 mmol) of 3- (3,4-dichlorobenzoyl) propionaldehyde in 60 ml of absolute ethanol was added 4 g (52 mmol) of ammonium acetate. The reaction mixture was refluxed for 20 minutes, then allowed to cool, most of the ethanol was evaporated on a rotary evaporator and 200 ml of a mixture of equal parts of dichloromethane and diethyl ether was added to the residue along with 50 ml of water. The layers were separated, the organic phase was dried over sodium sulfate and evaporated on a rotary evaporator. The residue was chromatographed on silica gel using hexane / ethyl acetate (3: 1) as eluent to give 4.6 g (83%) of the desired pyrrole as a brownish solid, mp 49-51 ° C.

Example 30

Preparation of 5- (3,4-dichlorophenyl) pyrrole-2-carbaldehyde

- 120

To 10 ml of dimethylformamide, presented in a 50 ml round bottom β flask, are stirred with stirring

Even under nitrogen, 0.6 ml (6.5 mmol) of phosphorus oxychloride was added dropwise via syringe. The reaction solution warms up spontaneously and turns slightly yellow. After stirring for 20 minutes, 1 g (4.7 mmol) of 2- (3,4-dichlorophenyl) pyrrole was added in portions and the resulting beige-colored suspension was stirred for 30 minutes and then heated at 50 ° C for 40 minutes. After cooling, a solution of 10 g (122 mmol) of sodium acetate in 15 ml of water was added to the reaction mixture, and the resulting mixture was stirred for 20 minutes. The precipitated beige precipitate was filtered from the reaction mixture and air dried for 20 hours to give 1.1 g (95%) of the substantially pure desired aldehyde melting above 200 ° C.

121

Example 31

Preparation of 5- (3,4-dichlorophenyl) pyrrole-2-carbonitrile

To a suspension of 1.5 g (6.2 mmol) of 5- (3,4-dichlorophenyl) pyrrole-2-carbaldehyde in 20 mL of water and 20 mL of ethanol was added 0.7 g (6.2 mmol) of hydroxylamine-O- sulfonic acids. The reaction mixture was heated under reflux for 1 hour, whereupon a gray precipitate formed. After cooling, the reaction mixture was filtered to give 1.5 g (99%) of substantially pure nitrile as a gray solid, mp 170-171 ° C.

122 Example 32

Preparation of 3,4-dibromo-5- (3,4-dichlorophenyl) pyrrole-2-carbonitrile

NBS

THF

To a solution of 0.5 g (2.1 mmol) of 5- (3,4-dichlorophenyl) pyrrole-2-carbonitrile in 20 ml of tetrahydrofuran was added portionwise under nitrogen, 0.8 g (4.2 mmol) of N-bromosuccinimide. The reaction mixture was stirred at 25 ° C for 30 minutes, then 10 mL of water and 40 mL of diethyl ether were added. The layers were separated, the organic layer was dried over sodium sulfate and evaporated on a rotary evaporator. The residue is chromatographed on silica gel, eluting with hexane / ethyl acetate (3: 1)

123 reagents. 0.5 g (60%) of the desired dibromopyrrole is obtained as a brown solid melting above 250 ° C.

Example 33

Preparation of 4-phenylpyrrole-3-carbonitrile

CN

H

To a mixture of 5.0 g (39 mmol) of cinnamonitrile and 7.6 g (39 mmol) of (p-tolylsulfonyl) methylisocyanide in 35 ml of dimethylsulfoxide and 65 ml of ether was added a suspension of 1.86 g of a 60% oil dispersion of sodium hydride ( 1.11 g (46 mmol) in 80 mL of ether.

The reaction mixture was allowed to react for 1 hour under nitrogen, then diluted with ether and water. The ether layer was separated, dried over magnesium sulfate and concentrated in vacuo. The oily residue, after chromatography on silica gel, eluting with a mixture of equal parts of chloroform and ethyl acetate, afforded 2.5 g of a cream-colored solid, from which, after recrystallization from ether / hexane, 1.15 g of the desired compound melting at 123 DEG-125 DEG. C.

Literature: Tet. Letters 5337 (1972); melting point

128 DEG-129 DEG

Example 34

Preparation of 2,5-dichloro-4-phenylpyrrole-3-carbonitrile

NC

- 125 -

To a stirred mixture of 4-phenylpyrrole-3-carbonitrile (0.66 g, 3.9 mmol) and dry tetrahydrofuran (20 ml) was added, while cooling in ice-water to 6 ° C, over a period of 4 minutes using a 0.66 ml syringe ( 1.11 g;

8.2 mmol) of sulfuryl chloride. The mixture was cooled to 5-10 ° C for 45 minutes, then the cooling bath was removed and the mixture was stirred for an additional 30 minutes. The reaction mixture is poured into 80 ml of ethyl acetate and 40 ml of water, the organic phase is separated, washed with water, dried over sodium sulphate and filtered through a short column of silica gel, which is washed with ethyl acetate. The combined filtrates were concentrated in vacuo to give a 0.95 & dark colored solid residue which, after recrystallization from chloroform, gave 0.42 g of off-white crystals melting at 195-196 ° C with decomposition.

Analysis for C H H ₆ Cl ₂ N ₂ requires 55.72% C, 2.55% H, 11.82% N, 29.91% Cl; Found: C, 55.66; H, 2.65; N, 11.69; Cl, 29.97.

126 Following the procedures described in Examples 33 and 34, the following analogs were prepared. To synthesis

2,6-dibromo-4- (p-chlorophenyl) pyrrole-3-carbonitrile was replaced with sulfuryl chloride and tetrahydrofuran with bromine in dioxane.

R X Y melting point (° C) 4-C1 Cl Cl 237 - 240 (decomposition) _4-CH3 Cl Cl 103-206 4-C1 Br Br > 245

- 127 Example 35

Ethyl 4- (p-chlorophenyl) pyrrole-3-carboxylate

Cl

A mixture of 23.5 g (122 mmol) of ethyl p-chlorocinnamate and 19.4 g (122 mmol) was added from a dropping funnel under nitrogen to a mixture of 5.63 g of a 60% suspension of sodium hydride in oil and 200 ml of dry ether under nitrogen. -tolylsulfonylmethyl isocyanide in 180 ml of ether and 80 ml of dimethylsulfoxide, the addition takes about 20 minutes

128, and the mixture boils gently under reflux. After stirring for a further 10 minutes, the reaction mixture was diluted with 100 mL of water and extracted four times with ether. The extract was dried over magnesium sulfate, concentrated in vacuo, and the solid residue was recrystallized from ethylene dichloride. 7.8 g of crystalline substance are obtained, m.p. 137 DEG-138 DEG.

Analysis: ^H Cl3 and ₂ ° ClN 2 requires 62.53% C 4.81% H 5.61% N 14.23% Cl; Found: C 61.31, H 5.12, N 5.32, Cl 14.57.

Concentration of the mother liquors from the crystallization yields an additional crude ester which is used for saponification.

Example 36

Preparation of 3- (p-chlorophenyl) pyrrole

- 129

A mixture of 22.0 g of crude ethyl 4- (p-chlorophenyl) pyrrole-3-carboxylate from the mother liquors (see the previous example) and the recrystallized product from the previous example was stirred at reflux with 150 ml of 10% for 2.5 hours. aqueous sodium hydroxide. The mixture was cooled, extracted with ether and then acidified to give a precipitate which was collected and dried. 11.6 g of product are obtained.

- 130 A mixture of 10.5 g of the above acid in 100 ml of β-ethanolamine is heated under reflux for 3 hours. After cooling, the reaction mixture was poured onto 400 ml of ice and the resulting mixture was extracted four times with chloroform. After drying over magnesium sulphate and clarifying with charcoal, the chloroform solution is concentrated in vacuo to a brown solid which is chromatographed on silica gel. Using a mixture of equal parts of ethyl acetate and hexane as eluent, 4.0 g of a white solid is obtained, m.p. 117-118 ° C.

Example 37

Preparation of 3- (p-chlorophenyl) pyrrole-2-carbaldehyde

- 131 -

Κ 0.86 g (12 mmol) of dimethylformamide in 10 [mu] l of ethylene dichloride was added, under cooling in ice, under nitrogen over 1.49 g (12 mmol) of oxalyl chloride in 10 ml of ethylene dichloride. The cooling bath was removed, the mixture was stirred for 15 minutes, then re-cooled in ice and 1.5 g (8.5 mmol) of 3- (p-chlorophenyl) pyrrole in 25 ml of ethylene dichloride was added over 20 minutes. The cooling bath was removed and after further stirring for 30 minutes the reaction mixture was poured into 50 ml of ice-water and 6 ml of 50% sodium hydroxide solution. The resulting mixture was extracted with ether and chloroform, the combined organic phases were dried over magnesium sulfate and concentrated in vacuo. The residue is purified by chromatography on silica gel using a mixture of equal parts of ethyl acetate and hexane as eluent. 0.63 g of off-white solid was obtained, which was used directly to convert to 3- (p-chlorophenyl) pyrrole-2-carbo-nitrile.

- 132 Example 38

Preparation of 3- (p-chlorophenyl) pyrrole-2-carbonitrile

To 0.63 g (3.1 mmol) of 3- (p-chlorophenyl) pyrrole-2-carbaldehyde in 10 ml of water was slowly added 0.52 g (4.6 mmol) of hydroxyl amine-O- with stirring under ice-cooling. sulfonic acid in 10 ml of water. After the addition was complete, the cooling bath was removed, the reaction mixture was heated for 25 minutes and then cooled. Excluded

The 133 solid product is a mixture of the above product and the starting aldehyde according to NMR spectroscopy. This mixture was treated with an additional 0.49 g (4.2 mmol) of hydroxylamine-O-sulfonic acid in a total of 30 mL of water in the same manner as above. The reaction mixture was heated at 60-70 ° C for 2 hours. After cooling, the precipitated solid material was collected and purified by silica gel chromatography eluting with ethyl acetate / hexane to give 0.40 g of a pink solid. mp 114-115 ° C.

Example 39.

Preparation of 4,5-dibromo-3- (p-chlorophenyl) pyrrole-2-carbonitrile

134 To 0.40 g (2.0 mmol) of 3- (p-chlorophenyl) pyrrole-2-carbonitrile in 25 ml of chloroform was added 0.63 g (4.0 mmol) of bromine. After 20 minutes, the precipitate formed was collected and recrystallized from ethyl acetate. 0.21 g of pink colored crystals melting above 250 ° C are obtained.

For C ^ HH ^ Br Br,3ClN requires C, 36.63; H, 1.39; Br, 44.38.

9.85% Cl, 7.77% N;

Found: C, 36.92; H, 1.32; Br, 44.62.

9.88% Cl, 7.50% N.

Example 40

Preparation of ethyl 5-bromo-4- (p-chlorophenyl) pyrrole-3-carboxylate

O

- 135 -

1.6 g (0.0064 mmol) of ethyl 4- (p-chlorophenyl) pyrrole-3-carboxylate are dissolved in 40 ml of tetrahydrofuran and 1.14 g (0) are added in small portions at 25 to 28 ° C. N-bromosuccinimide. After complete addition, the reaction solution was stirred at room temperature overnight, then concentrated in vacuo and the solid residue was partitioned between water and ether. The ether layer was separated and dried (MgSO4) to give 1.9 g (90%) of a white solid which, after purification by stirring in hexane / ethyl acetate (80 x 20) and isolating the insoluble solid, gave 1.3 g (90%). M.p. 161-164 ° C.

H, 3.34; N, 4.26.

24.33% Br, 10.80% Cl;

Found: C, 47.39; H, 3.38; N, 4.12.

Br, 24.29. Cl, 10.77.

- 136 Example 41

Preparation of 5-bromo-4- (p-chlorophenyl) pyrrole-3-carboxylic acid

Ethyl 5-bromo-4- (p-chlorophenyl) pyrrole-3-carboxylate (15 g, 0.045 mol) was added to 200 ml of 10% sodium hydroxide and the resulting suspension was heated to reflux. After dissolution of all solids, the reaction mixture was refluxed for a further 40 minutes, then cooled.

137 is filtered and the filtrate is acidified. The white precipitate formed is collected and dried. 8.0 g (58%) of a solid melting above 205 ° C are obtained, whose NMR spectrum (perdeuterodimethylsulfoxide) contains a signal for the pyrrole proton at cT 7.52. The mass spectrum also corresponds to the monobrominated product

Example 42

Preparation of 2-bromo-3- (p-chlorophenyl) pyrrole

138 g of 5-bromo-4- (p-chlorophenyl) pyrrole-3-carboxylic acid (8.0 g, 0.026 mol) are added to 24 ml of aminoethanol, and the suspension is slowly heated to 110-120 ° C and at this temperature. hold for 1 hour. The reaction solution was cooled, poured into water and extracted with ether. A sample of the ether extract was subjected to thin layer chromatography (hexane-ethyl acetate 75:25). The chromatogram contains a major spot progressing faster and slower as a secondary spot. After the usual work-up, 4.0 g (56%) of a dark colored solid, 2-bromo-3- (p-chlorophenyl) pyrrole, was obtained from the ether phase which was used immediately to prepare 5-bromo-4- (p (chlorophenyl) pyrrole-2-carbonitrile.

Example 43

Preparation of 5-bromo-4- (p-chlorophenyl) pyrrole-2-carbonitrile

- 139 -

Freshly prepared 2-bromo-3- (p-chlorophenyl) pyrrole weighing 4.0 g (0.015 mol) was dissolved in 25 ml dry dimethoxyethane and 3.08 g (0.022 mol) was added while maintaining the temperature below 25 ° C. chlorosulfonyl isocyanate. The reaction solution was stirred overnight, then 6 ml of dimethylformamide was added thereto, and the mixture was stirred for 3 hours. After pouring the solution into water, 3.8 g (90%) of a brown solid precipitated, from which, after chromatography on a dry silica gel column, 1.4 g (33%) of a white solid melting at 202-204 ° C were obtained. A mixture of hexane and ethyl acetate (80:20) was used as eluent.

For C ^ HH ,BrClNg requires C, 46.90; H, 2.13; N, 9.95.

12.61% Cl, 28.39% Br;

Found: C, 47.20; H, 2.09; N, 9.80.

12.36% Cl, 27.42% Br.

140 Example 44

Preparation of 3,5-dibromo-4- (p-chlorophenyl) pyrrole-2-carbonitrile

Dissolve 2.2 g (0.0078 mol) of 5-bromo-4- (p-chlorophenyl) pyrrole-2-carbonitrile in 30 ml of dry dioxane, heat the solution with a solution of 1.3 g (0.008 mol) of bromine in 20 ml. ml of dioxane and then stirred at room temperature overnight. The reaction mixture was poured into water, whereupon 2.6 g (92%) of a yellow-red solid material precipitated. Part

This material (1.6 g) was purified by flash chromatography (hexane / ethyl acetate 75:25).

0.8 g of a gray solid is obtained, m.p. 191-194 ° C.

Analysis: for C ^^^H BrBrgClNg

calculated 36.61% C, H, 1.38 % N, 9.84% Cl, 44.3% Br; found 37.46% C, H, 1.25; 7.41 % N, 9.53% Cl, 42.99% Br. At klad 45

Preparation of 3- (3,4-dichlorophenyl) -4-nitropyrrole

142 -

2.66 g of a 60% suspension of sodium hydride in oil (66 mmol) was washed with dry ether and the hydride was suspended in 150 ml of dry ether. A mixture of 12.0 g (5.5 mmol) was added to the suspension over 15 minutes.

3,4-dichloro-p-nitrostyrene and 10.8 g (5.5 mmol) of (p-tolylsulfonyl) methylisocyanide in 50 mL of dimethylsulfoxide and 150 mL of ether. The reaction mixture was stirred for 1.5 hours and then diluted with 150-200 mL of water and additional ether. The ether layer was separated and, after drying over magnesium sulfate, concentrated in vacuo. The residue, 10.6 g of crude product, was purified by chromatography on silica gel using chloroform / ethyl acetate (4: 1) as eluent. A solid product fraction of 7.2 g is obtained which, after recrystallization from a mixture of chloroform, ethyl acetate and hexane, yields 3.0 g of a yellow solid melting at 187-188 ° C with decomposition.

- 143 Analysis: calculated for ^C 6 ^H 6 ^Cl 2 ^N 2 ° 2: 46.72% C, 2.35% H, 10.90% N; Found: C, 46.96; H, 2.60; N, 9.77.

Example 46

Preparation of 2,5-dichloro-3- (3,4-dichlorophenyl) -4-nitro pyrrole

To a mixture of 2.5 g (9.7 mmol) of 3- (3,4-dichlorophenyl) -4-nitropyrrole with 200 mL of chloroform heated to about 40 ° C was added 2.95 g (22 mmol) over 1 minute. sulfuryl chloride. After an additional hour the reaction was complete

The mixture is diluted with 100 ml of saturated sodium bicarbonate solution and 300 ml of ether, the organic layer is separated, dried over magnesium sulphate and concentrated in vacuo. The brown solid residue is chromatographed on silica gel using chloroform / ethyl acetate (4: 1) as eluent. The orange solid fraction was first recrystallized from chloroform and then re-chromatographed on silica gel using chloroform / ethyl acetate (4: 1) as eluent. 0.36 g of a yellow solid is obtained, m.p. 193-194 ° C.

2,5-dichloro-3-nitro-4-phenylpyrrole melting at 193-194 ° C with decomposition as described in Examples 45 and 46 above.

Example 47

Preparation of 5- (p-chlorophenyl) pyrrole-2,4-dicarbonitrile

145 -

The cyanopyrrole prepared according to Example 4 was dissolved in 50 ml of dry dimethoxyethane and 3.39 g (0.024 mol) of chlorosulfonyl isocyanate was added. As the exothermic reaction proceeds, the temperature rises and the mixture needs to be cooled somewhat. After stirring at room temperature for 3 hours, 6-7 ml of dimethylformamide are added, the solution is stirred for 4 hours and then poured into water, whereupon 3.4 g (100%) of a white solid material precipitates. A 1.0 g sample of this material was purified by dissolving in ethyl acetate and pouring the solution through a pad of silica gel in a 60 mL filter funnel. Concentration of the filtrate gave 0.7 g of a white solid, m.p. 235-240 ° C.

Following the procedure of Example 47, the following analogs were prepared.

- 146 -

R L melting point (° C) 3-C1 4-C1 > 255 H 4-OCF ₃ 185-190 H 4-CF 3 180-185

Example 48

Preparation of 3-broo-5- (p-chlorophenyl) pyrrole-2,4-dicarbonitrile

- 147 -

1.0 g (0.004 mol) of 5- (p-chlorophenyl) pyrrole-2,4-dicarbonitrile was dissolved in 20 ml of dioxane and a solution of 0.8 g (0.005 mol) of bromine in 10 ml of dioxane was added. The reaction solution was stirred at room temperature for several hours and then poured into water to precipitate 1.2 g (100%) of a white solid. This solid melts above 225 ° C and its mass spectrum is consistent with the desired structure.

Following the procedure described in Example 48 above, the following additional compounds were prepared.

148 -

R L melting point 3-C1 4-C1 > 250 H 4-OCF3 218-223 H 4-CF ₃ 239-241

Example 49

Preparation of bromo-araonitrile

NC

CN

Br ₉ / CHCl 3

CN (-HBr) / = \

NC Br

- 149 15.6 g (0.2 mol) of fumaronitrile in 150 ml of chloroform are heated to reflux under nitrogen, resulting in a clear solution to which a solution of 5.3 ml (0.2 mol) is added dropwise over 30 minutes. of bromine in 25 ml of chloroform. This addition slowly decolors and releases acidic vapors (according to the pH of the paper). The reaction solution was stirred for an additional 90 minutes, most of the color disappearing, then cooled and the solvent was evaporated under reduced pressure. There remains an amber oil whose mass roughly corresponds to the theory calculated for bromofumaronitrile. The oily material was distilled in a bead distillation apparatus at a pressure of 27 Pa while maintaining the temperature below 120 ° C (rapid decomposition of the material above this temperature). A semi-solid residue is obtained, which slowly changes to a waxy amber colored, melting at 43-47 ° C.

For C ^4Hr HBNr requires C, 30.57; H, 0.64; N, 17.83.

Found: C, 29.13; H, 0.75; N, 16.94.

150 Example 50

Preparation of 2-phenylpyrrole-3,4-dicarbonitrile

To a solution of 4.7 g (0.03 mol) of bromofumaronitrile and 7.1 g (0.03 mol) of N- (trimethylsilyl) methyl-S-methylbenzenethioimidate in 35 ml of hexametbylphosphoramide was stirred in a single atmosphere at room temperature under a single atmosphere at room temperature. 1.6 ml (0.09 mol) of water was added to the batch, which was rinsed with 10 ml of hexamethylphosphoramide. An exothermic reaction begins almost immediately in the solution, as a result of which the temperature rises rapidly to 100 ° C and then drops. The resulting dark red solution

The mixture was stirred at room temperature for 20 hours and then poured into ice water. A resinous material precipitates which slowly turns to a beige solid, which is filtered off and washed on the filter with cold water and dried. After further drying in a vacuum oven at 60 ° C, the product is recrystallized twice from ethylene dichloride under clarification with activated charcoal to give a white powdery solid, m.p. 197-200 ° C.

H, 3.63; Found: C, 74.45; H, 3.84;

N, 21.76; 21.61% N.

Example

Preparation of 2-bromo-5-phenylpyrrole-3,4-dicarbonitrile

NC

CN

- 152 -

To 35 ml of chloroform, 1.4 g (0.0075 mol) of 2-phenylpyrrole-3,4-dicarbonitrile was added under nitrogen, most of the solid material being dissolved. 0.4 ml (0.008) solution was added over 20 minutes. mol) of bromine in 5 ml of chloroform. Initially the color of the mixture disappears rapidly, but as the resin product begins to precipitate, the coloration persists. The reaction mixture was stirred at room temperature for 30 minutes and then refluxed, whereupon the resinous material turned to a solid product. The reaction mixture was heated to reflux for 90 minutes, then cooled, and its sample analyzed by high performance liquid chromatography, indicating that about 60% of the starting material remained in the mixture. 0.2 ml (0.004 mol) of fresh bromine was added in one portion and refluxing was continued for a further 45 minutes. After this time, the mixture contains 10% starting material. An additional 0.2 ml was added

153 (0.004 mol) of fresh bromine (bromine is added to the refluxing slurry) and heating to reflux is continued for 30 minutes. The resulting suspension was cooled, stirred at room temperature for 18 hours, then the solvent was evaporated under reduced pressure. A greenish solid is obtained, from which a dark colored residue remains after extraction with hot chloroform. The extract is clarified with activated carbon and filtered while hot. A white precipitate began to precipitate from the clear yellow filtrate. After cooling to -10 ° C, the white solid was filtered off.

For ^C 12 ^H 6 ^BrN 3 calculated C 52.94, H 2.21, N 15.44, Br 29.41; Found: C, 51.64; H, 2.35; N, 14.91; Br, 28.69.

Mp 225-258 ° C.

Example 52

Preparation of 2- (3,4-dichlorophenyl) -5-nitropyrrole-3-carbonitrile

- 154 -

To a mixture of 50 ml of acetic anhydride and 0.6 ml of 90% nitric acid was added 3.0 g (0.013 mol) of 2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile, causing a very slight increase in temperature. The reaction mixture was slowly warmed to 30 ° C and maintained at 30-33 ° C

- 155 until all solid material has gone into solution. Gradually, a new solid product begins to precipitate. The mixture was stirred at room temperature for 2-3 hours and then poured into ice water to decompose acetic anhydride. After stirring for 1 hour, the mixture was filtered and the solid product dried. 2.9 g (82%) of crude product are obtained, of which 1.5 g is purified by silica gel chromatography using hexane / ethyl acetate (75:25) as eluent. 0.7 g of a yellow solid is obtained, m.p. 228-231 ° C.

Analysis calculated for ^C n ^ ^ 5 ^{< 1 1N} 2O °: C, 46.80; H, 1.77; N, 14.89; Cl, 25.17; Found: C, 46.50; H, 1.96; N, 14.27; Cl, 24.30.

In the same way 2- (p-chlorophenyl) pyrrole-3-carbonitrile was used as starting material to give 2- (p-chlorophenyl) -5-nitropyrrole-3-carbonitrile, m.p. 201-206 ° C. 2- (p-Trifluoromethylphenyl) pyrrole-3-carbonitrile also yields 2- (p-trifluoromethylphenyl) -5-nitropyrrole-3-carbonitrile as described above, m.p. 164-165.5 ° C.

Example 53

Preparation of 4-bromo-2- (3,4-dichlorophenyl) -5-nitropyrrole-3-carbonitrile

- 156 -

Cl

0.5 g (0.0017 mol) of 2- (3,4-dichlorophenyl) -5-nitropyrrole-3-carbonitrile is dissolved in 10 ml of dry dioxane and dioxane

- 157 solution of 0.28 g (0.0017 mol) of bromine. The resulting solution was stirred overnight and then poured into water to precipitate 0.54 g (88%) of a reddish-brown solid which, after recrystallization from 5 ml of acetonitrile, yielded 0.26 g of a reddish-brown solid, m.p. .

For C 1 %H ^ BrClCl3NqOg requires C, 36.57; H, 1.10; N, 11.63.

Br, 22.13; Cl, 19.67;

Found: C, 36.46; H, 1.29; N, 11.50.

Br, 21.63; Cl, 19.28.

Using the procedure of Example 53, 2- (p-chlorophenyl) -5-nitropyrrole-3-carbonitrile was obtained

4-Bromo-2- (p-chlorophenyl) -5-nitropyrrole-3-carbonitrile, m.p. 180-185 ° C.

Example 54

5- (3,4-Dichloro-phenyl) -4-nitropyrrole-2-carbonitrile

- 158 -

To a suspension of 1.2 g (5.1 mmol) of 5- (3,4-dichlorophenyl) pyrrole-2-carbonitrile in 25 ml of acetic anhydride at 30 ° C under nitrogen is added dropwise 0.3 ml (5.1 mmol) 90% nitric acid. As a result of the ongoing exothermic reaction, the temperature rises to 45 ° C and the mixture becomes a green colored solution. The reaction mixture was stirred for 2 hours then poured into 50 ml

- 159 water and mix vigorously for 5 minutes. The precipitated beige precipitate was filtered off, dissolved in a minimum volume of acetone and chromatographed on silica gel using hexane / ethyl acetate (3: 1) as eluent. 1.2 g (84%) of the desired nitropyrrole are obtained as an off-white solid, melting above 200 ° C.

Example 55

3-bromo-5- (3,4-dichlorophenyl) -4-nitropyrrole-2-carbonitrile

- 160 To a suspension of 0.6 g (2.1 mmol) of 5- (3,4-dichlorophenyl) -4-nitropyrrole-2-carbonitrile in 10 ml of dioxane at 25 ° C under nitrogen are added dropwise a solution of 0.3 g. (2.1 mmol) of bromine in 5 mL of dioxane. The reaction mixture is stirred overnight, 50 ml of water are added thereto, whereupon a yellow solid precipitates, which is filtered off and dried in a vacuum oven at 45 DEG C. under 50 mm Hg. 0.7 g (90%) of the desired bulk pyrrole was obtained as a yellowish solid melting above 200 ° C.

Example 56

4- (p-chlorophenyl) -2- (trifluoromethyl) -2-oxazolin-5-one

To 11.4 g (0.06 mol) of powdered 2- (p-chlorophenyl) glycine was added in one portion 1.7 ml (0.012 mol) trifluoroacetic anhydride, resulting in an immediate temperature rise to about 40 ° C and formation of a yellow color on the surface of a solid material.

As the mixture slowly warms to 70 ° C, some of the solid material dissolves into an orange amber oil. All solid material dissolves in about 2 hours and heating is continued for 1 hour. Solvent

To evaporate under reduced pressure on a rotary evaporator, toluene was added twice to the residue, which was always evaporated under reduced pressure. Trifluoroacetic acid is still visible from the final residue. The yellow semi-solid, which is formed in theoretical yield, has a purity of &gt; 90% according to high performance liquid chromatography. This material is the title compound and is used for the next reaction without further purification.

Example 57

Preparation of 2- (p-chlorophenyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile

2.5 g (0.01 mol) of 4- (p-chlorophenyl) -2- (trifluoromethyl) -2-oxazolin-5-one are dissolved in 50 ml of nitromethane and 8.0 ml ( 0.10 mol) of 2-chloroacrylonitrile. The reaction solution was stirred under reflux for 18 hours under nitrogen and the resulting reddish brown solution was cooled to -5 ° C in ice-acetone, whereupon a precipitate formed which was filtered off and washed with a small amount of cold nitromethane. Resultant

162 reddish-brown solid material gave, after recrystallization from hot ethylene dichloride, 1.8 g (56% of theory) of the desired product as white crystals melting at 238-241 ° C with decomposition.

Using the appropriate arylglycine in the reaction described in Example 55 and then following the procedure described in this Example, the following 2-aryl-5- (trifluoromethyl) pyrrole-3-carbonitriles were prepared.

R L melting point (° C) H H 215-218 H 4-CH-, 191-193 H 4-OCH ₃ 168 - 180 (decomposition) 3-C1 4-C1 245 - 246 (decomposition) H 4-CF ₃ 218-219

- 163 Example 58

Preparation of 4-bromo-2- (p-chlorophenyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile

A suspension of 1.6 g (0.005 mol) of 2- (p-chlorophenyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile in 25 ml of acetic acid was heated until all solid material dissolved at about 60 ° C. A solution of 0.8 ml (0.015 mol) of bromine in 10 ml of acetic acid was added dropwise over 15 minutes to the resulting clear solution. The reaction solution was refluxed for 6 hours and then stirred at room temperature for 18 hours. High performance liquid chromatography of the reaction mixture sample indicated about 80% conversion to the desired product. The mixture was again heated to reflux and an additional 0.5 mL (0.01 mol) of bromine in 5 mL of acetic acid was added. After refluxing for 3 hours, the conversion to the desired product is greater than 95%. The reaction mixture is cooled and the solvent is evaporated off under reduced pressure on a rotary evaporator. Toluene was added to the dark gray solid, which was then evaporated under reduced pressure. However, the residue still smells of acetic acid.

Dissolve the material in 75 ml of hot toluene to a turbid solution, which is clarified with activated carbon and filtered. A white solid precipitated from the pinkish filtrate upon cooling to room temperature.

After cooling in the freezer, the solid product is filtered off and, after washing with hexane, dried first on the filter and then in a vacuum oven at 45 ° C. It is obtained

1.2 g (ca. 60% of theory) of product melting at 247-250 ° C with decomposition.

For C ^ HHjBrClF ^Ng requires C, 41.20; H, 1.43; N, 8.01.

Br, 22.89; Cl, 10.15; F, 16.31;

Found: C 41.27, H 1.48, N 8.10

Br 22.92, Cl 10.16, F 16.03%.

The following additional compounds were prepared by bromination of the corresponding 2-aryl-5- (trifluoroethyl) pyrrole-3-carbonitrile, prepared as described in Example 57, as described above.

165 -

R L melting point (° C) H H 235-238 H _4-CH3 244-245 3-C1 4-C1 218-223 H 4-CF ₃ 225-226 Example 59

Preparation of 2- (4-chlorophenyl) -5-trifluoromethylpyrrole-3,4-dicarbonitrile

- 166 O

To 2.0 g (0.011 mol) of (4-chlorophenyldglycine) was added 3.1 ml (0.022 mol) of trifluoroacetic anhydride in a single portion, giving an immediate yellow color and to some extent refluxing. heat to boil under

- 167 with a reflux condenser, all of the solid being dissolved into a yellow-orange solution, which was heated for a further 2 hours. The reaction mixture was cooled and the solvent was evaporated under reduced pressure. Toluene was added twice to the residue, which was always evaporated under reduced pressure. A very thick oily residue of 1800 cm @ -1 is obtained.

This residue was dissolved in 40 ml of nitromethane, except for small insolubles, and 2.7 g (0.018 mol) of bromofumaronitrile was added in one portion. The resulting solution was heated to reflux for 18 hours, whereupon it turned dark red. The solvent was evaporated under reduced pressure and the dark colored residue was dissolved in dichloromethane. A small amount of insoluble material was removed by filtration. The material was fractionated by chromatography on a dry silica gel column using 3% 2-propanol in dichloromethane as eluent. The eluate was collected in appropriate fractions. Evaporation of one fraction gave the desired product as a yellow solid which, after recrystallization from acetonitrile with decolorizing charcoal, afforded 0.2 g of a pale yellow solid melting partially with decomposition at 238-241 ° C.

Example 168

A solution of 1.39 mol (250.0 g) of p-chlorobenzoylacetonitrile, 203 ml (185.9 g; 1.39 mol) of 2,2-diethoxy ethylamine and 1300 ml of dry toluene was heated to reflux for 20 hours under magnetic stirring. The resulting water was collected in a Dean-Stark well (23.8 ml; 95.2% of theory). The hot cloudy, dark brown solution containing a large amount of undissolved solids is filtered through a pad of diatomaceous earth, the filtrate is diluted with 200 ml of ethyl acetate and again filtered through a silica gel column (7 cm x 13.5 cm). Concentration of the filtrate in vacuo afforded 354.3 g (86.4% yield of crude product) of a clear dark oil which slowly solidified. This solid product is recrystallized from hot cyclohexane,

169 to give 324.2 g (79.1% yield) of an orange-colored waxy solid. According to NMR spectroscopy, this product was a mixture of 78% (Z) - and 23% (E) -isomers of p-chloro-p - [(formylmethyl) amino] cinnamonitrile diethyl acetal, melting at 60-72 ° C.

The following analytical data are available for another similarly prepared sample.

IR (nujol suspension) _max : 3325 (s), 3065 (m),

2197 (with), 1600 (with), 1530 (with), 1314 (m), 1265 (m), 1173 (m), 1154 (m), 1128 (with), 1100 (with), 1060 (with), 1022 (with), 939 (m),

895 (m), 844 (s), 768 (m), 730 (m) ^cm-A

@ 1 H-NMR (chloroform, .delta.): 7.47 (d, J = 8.6 Hz, 2.12H, two aromatic protons), 7.37 (d, J = 8 Hz, 2.12H, two aromatic for tones) ), 5.10 (E) and 4.86 (Z) (bt, 1.25H, one NH group proton), 4.69 (Z) and 4.60 (E) (t, J = 5.1 Hz) , 1, O5H, one methine proton on acetal carbon), 4.07 (E) and 4.05 (Z) (s, 0.83H, proton at the 0-position of ensmin), 3.71 (E) and 3, 68 (Z) (q, J ^and 7.1 Hz, 2.22H, two methylene protons of one of the two ethoxy groups),

- 170 3.56 (Z) and 3.53 (B) (q, J = 7.1 Hz, 2.22H, * two methylene protons of one of the two ethoxy groups), 3.18 (t, J »5.1) Hz, 1.77H, two methylene protons of the ethylene acetal group), 1.20 (t, J = 7.1 Hz, 4.9OH, six methyl protons of two ethoxy groups).

C-NMR (chloroform, values): 161.21 (α-enamine carbon), 136.29 (Z) and 134.60 (E) (either Ο _χ or phenyl ring), 134.08 (Z) and 132, 30 (E) (beech or phenyl ring)

129.34 (Z) and 129.89 (R) (either C _{2} g} or C _{3} 5 of the} phenyl ring), 128.94 (Z) and 128.63 (B) (either C _{2 g} or C _{3 g)} phenyl ring),

121.19 (Z) and 119.50 (E) (nitrile carbon), 99.43 (Z) and 100.63 (E) (O-enamine carbon), 61.88 (Z) and 63.25 (E) E) (methane of the acetal group), 62.64 (Z) •

and 63.03 (E) (methylene carbons of ethoxy), 46.32 (Z) and 47.33 (E) (methylene carbons).

carbon ethylamine groups), 15.26 (methy- ethoxy carbons groups). Microanalysis (Molecular Weight): calculated: 61.11% C, 6.50% H, 9.51% N, 12.03 % whose; Found: C, 61.25; H, 6.25. 9.34% N, 12.35 % Cl.

171

By replacing p-chlorobenzoylacetonitrile with the appropriate benzoylacetonitrile and / or 2,2-diethoxyamine each with the corresponding 2,2-dialkoxyethylamine containing from 1 to 4 carbon atoms in each alkyl moiety, the following compounds are obtained as described above.

- co-ch ₂ cn

H ₂ NCH ₂ (OAlk) ₂ toluene

-H "

Alk = C1-C4alkyl

- 172 melting point (° C)

LMR (OAlk) ₂

Η H p-CH ₃ OCO

H p-CH ₃ H

H P-CH ₃ K

H m-Cl p-Cl

Η H p-OCF ₃

Η H p-CF ₃ (og ₂ h ₅ ) ₂ (oc ₂ h ₅ ) ₂ (oc ₂ h ₅ ) ₂ (oc ₂ h ₅ ) ₂ (OCH-j) ₂ (OCH ₂ ) ₂ (° ^C 2 ^H 5> 2 (oc ₂ h ₅ ) ₂ (0C ₂ h ₅ ) ₂

- 73

- 69 red-orange semi-solid

Orodukt *

- 70

173

Example 61

2- (p-chlorophenyl) pyrrole-3-carbonitrile

To 108 ml of trifluoroacetic acid was added with stirring at 23 ° C over 45 minutes 54.00 g (0.183 mol) of solid p-chloro-3-C (formylmethyl) amino] cinnamonitrile diethyl acetal. During the addition, an exothermic reaction occurs during which the temperature rises to 38 ° C and a solid precipitate begins to precipitate 32 minutes after the start of the addition. The reaction mixture was stirred for 30 minutes

174 was stirred at room temperature and then vacuum filtered. The solid material was washed first with trifluoroacetic acid, then with a mixture of ethyl acetate and hexane and finally with hexane. 16.83 g (45.4%) of an off-white solid, m.p. 165-166 ° C. The following analytical data were obtained for an analogously prepared sample.

IR (nujol suspension) Ό: 3275 (bs), 2225 (s),

1502 (s), 1410 (m), 1275 (m), 1200 (m)

1108 (s), 1032 (m), 999 (m), 908 (m),

843 (a), 752 (a), 722 (a), 695 (a),

620 (s) cm ^-1 .

K-NMR (acetone, cZ values): 11.22 (very wide singlet 0.99 H, one proton of the NH group in the pyrrole) 7.82 (d, J = 8.9 Hz, 2.46 Hz, two aromatic phenyl protons), 7.51 (d, J = 8.9 Hz, 2.46 H, two aromatic phenyl protons), 7.02 (t, J = 2.6 Hz, 1.01 H, one). proton per pyrrole), 6.58 (t, J = 2.6 Hz, 0.77H, one proton per pyrrole).

C-NMR (acetone, values): 137.73 ₍₂ C pyrrole)

134.42 (p-chlorophenyl at C 6), 129.93 (meth carbons at positions 3 and 5)

- 175 phenyl ring), 121,21 (C 1 -pyrrole),

117.93 (nitrile carbon), 113.78 (C 1-4 pyrrole), 90.86 (C 1-4 pyrrole).

Microanalysis (MW 202.64):

C, 65.19; H, 3.48; N, 13.83; Cl, 17.50; Found: C, 64.18; H, 3.52; N, 13.63; Cl, 17.74.

Using the procedure described above, optionally substituting trifluoroacetic acid with concentrated hydrochloric acid, the following compounds are obtained.

4-C1 165 - 166 conc. HCl 3,4-di-Cl 216 - 221 cf ₃ cooh 2-C1 156 - 157 cf ₃ cooh 4-0CF. 143 - 145 CF-, COOH

cf ₃ cooh

176 -

M or / and R melting point (° C) the acid used 4-CF ₃ 179-180 cf ₃ cooh 2,4-di-Cl 197-199 cf ₃ cooh 3-C1 150-156 cf ₃ cooh 4-CN 210-212 cf ₃ cooh 4-F 167-170 conc. HCl 4-SO ₂ CH ₃ 221-221,5 cf ₃ cooh 3,4-di-F 173-175.5 cf ₃ cooh 3-CF ₃ 166-168 cf ₃ cooh 4-COOCH ₃ 155.5-158 cf ₃ cooh _4-CH3 117-137 CF ₃ COOH 4-NO ₂ 174-177 CF ₃ COOH

Example 62

4,5-dichloro-2- (p-chlorophenyl) pyrrole-3-carbonitrile

177 -

To solution 16; 83 g (83.1 mmol) of 2- (p-chlorophenyl) pyrrole-3-carbonitrile in 450 ml of glacial acetic acid are added dropwise over 13 minutes at 36 DEG C. with 14.7 ml (24.70 g; 183.0 mmol) of sulfuryl chloride. During the addition, a slight exothermic reaction associated with a temperature rise to 39 ° C occurs. After a further 16 minutes, the reaction mixture was filtered under vacuum and the solid material was washed first with acetic acid and then with water. This solid melts after recrystallization from hot ethyl acetate at 259-261 ° C.

178

Further workups of this product are prepared in an analogous manner. The following section provides analytical data for one of these products.

IR (nujol suspension) J: 3170 (bs), 3100 (m), U1 SX «

2225 (s), 1508 (m), 1097 (s), 835 (s),

717 (m), 660 (m) cm ^- ^.

H-NMR (dimethylsulfoxide, d ') values: 7.72 (d, J = 8.6 Hz, 2.00 H, two aromatic protons),

7.56 (d, J = 8.6 Hz, 2.00 H, two aromatic protons).

C-NMR (dimethylsulfoxide, values: 136.01 (C2 pyrrole), 133.92 ( _4- p-chlorophenyl), 129.09 (carbons at positions 3 and 5 of p-chlorophenyl),

127.41 _(C4 p-chlorophenyl), 127.11 (0 _χ p-chlorophenyl), 114.49 (nitrile carbon. Rest), 114.10 (C-pyrrole), 110.92 (C-pyrrole) , 90.09 (C 1 of pyrrole).

*

Microanalysis (Mol. Weight 271.54):

calculated: 48.65% C, 1.86% H, 10.32% N, 39.17% Cl; Found: C, 49.22; H, 2.12; N, 9.85; Cl, 39.03. - 179

Example 63

4,5-dibromo-2- (α, α, α-trifluoro-p-tolyl) pyrrole-3-carbonitrile

To a stirred mixture of 0.8 g of 2- (α, α, α-trifluoro-p-tolyl) pyrrole-3-carbonitrile in 70 mL of chloroform was added 2 mL of bromine. The reaction mixture was stirred overnight to give a white solid which was filtered off. This product, melting above 230 ° C, is a single component according to thin layer chromatography (a mixture of equal parts of ethyl acetate and hexane).

180

For C ^ gHHBBrgF ^Ng requires C, 36.55; H, 1.27; N, 7.11; Br, 40.61. Found: C, 36.40, H, 1.08, M, 6.99, Br.

The following compounds were prepared as described above by substituting 2- (α, α, α-trifluoro-p-tolyl) -pyrrole-3-carbonitrile with an appropriately substituted phenylpyrrole-3-carbonitrile.

L M R X Y melting point: (° C &gt;) H H 4-NO ₂ Br Br 274-277 H H 4-F Cl Cl : 220 H H 4-F Br Br 220 H H 4-SO ₂ CH ₃ Cl Cl > 230 H 3-F 4-F Cl Cl > 230

181

L M R X Y melting temperature (° C) Η 3-F 4-F Br Br > 220 2-C1 3-C1 4-C1 Cl Cl 2-Br 3-Br 4-Br Br Br H H 4-OCF ₃ Cl Cl 222-225 »T rt H 4-0CF ₃ Br Br H H 4-0C7 ₃ Cl H τ T Γχ H 4-CN Br Br > 230 τ r n H 4-CN Cl Cl > 240 H H 4-SO ₂ CxH ₃ Br Br > 230 H H 4-NO ₂ Cl Cl 246-249 H 3-01 4-C1 Br Br > 260 and H 3-CF ₃ Cl Cl > 230 H H 4-CCCH ₃ Cl Cl 251-254 4 2,3- CH = CH- Cl Cl 244-247 H ťx _4-CH3 Cl Cl 215-217 H 2-C1 4-01 Br 3r > 230 and H 3-C1 Cl Cl ra 230 íí 2-C1 4-C1 Cl Cl > 230

182

L M R X Y melting point (° C) H H 4-C1 Br Br 273-274 H H 2-C1 Br Br > 230 H H 4-CF ₃ Cl Cl > 230 H H 4-Br Cl Cl ? 235 H H 2-C1 Cl Cl y 230 H 3-C1 4-C1 Cl Cl ^ 235 H H H Cl Cl 254-255

Example 64 α- (2,2-Diethoxyethylamino) -p-nitrostyrene and 3-nitro-2-phenylpyrrole

H ₂ NCH ₂ CH (OEt) ₂

186

LMR (OAlk) ₂

Η H p-CH ₃ OCO

HP ' ^CH 3 ^hr

H

H p-Cl m-OCH ₃ p-OCH ₃

H p-CH ₃ H

Η H P-CF ₃ (OC ₂ H _{5) 2} (0C ₂ H _{5) 2} (OC ₂ H _{5) 2} (0C ₂ H _{5) 2} (OCH _{3) 2} (OCH _{3) 2} (OC ₂ H _{5) 2}

Example 65

2,3-dichloro-4-nitro-5-phenylpyrrole

187 -

To a mixture of 1.56 g (0.0083 mol) of 3-nitro-2-phenylpyrrole and 60 ml of dioxane was added dropwise 25.9 g (0.0182 mol) of commercial sodium hypochlorite while cooling in ice. The reaction mixture was stirred for 45 minutes, then acidified with concentrated hydrochloric acid and added to water and diethyl ether. The layers were separated, the upper organic layer was washed with water and, after drying with anhydrous magnesium sulfate, concentrated in vacuo. 2.21 g of a yellow solid are obtained which, after purification by chromatography on silica gel, eluting with ethyl acetate / hexane with an increasing portion of ethyl acetate, gives 0.77 g (36%) of the title compound, m.p. 190-190. M.p.

For ^C 10 ^H 6 ^N 2 ^O 2 ^Cl 2 requires C, 46.72; H, 2.35; N, 10.90.

Found: C, 46.96; H, 2.86; H, 10.02.

188

The following examples illustrate the insecticidal, acaricidal and nematicidal activity of the compounds of the invention.

Example 66

Insecticidal and acaricidal activity tests

All tests are performed using technical grade material. The concentrations indicated are those of the active ingredient. All tests are performed at 27 ° C.

Spodoptera eridania test (3rd instar larvae)

7 - 8 cm long bean leaf leaves are immersed in the test substance suspension, left under stirring for 3 seconds and then allowed to dry in a fume hood. The treated leaves were then placed in petri dishes (100 x 10 mm) at the bottom of which were placed moist filter paper and each containing 10 Spodoptera eridania larvae (3rd instar). After 5 days, the experiment is evaluated to detect morbidity, reduced feeding, and / or any abnormal larval development.

Spodoptera eridania - reaidual effect (7 days)

The plants treated as described in the above test are maintained for 7 days in a greenhouse under illumination with high intensity lamps corresponding to twice the brightness of a bright sunny day in June in New Jersey, simulating a 14 hour day duration. After 7 days, the leaves of the plants were subjected to the test described above.

Aphis fabae (Poppy Aphid)

Dishes containing a single plant of Tropaeolum sp., About 5 cm high, are infested with about 100 to 200 specimens of the aphid 1 day before the start of the test. Each dish is then sprayed on a rotary table in a fume cupboard at 4 rpm using a DeVilbis atomizer. Spraying is carried out for two revolutions of the stage. The spray nozzle is about 15 cm away from the plant and after190 spraying is directed to reach the entire plant and aphids. The treated plates were placed on the side of the white enamel trays and held in this position for 2 days, after which the mortality was assessed.

Tetranychus urticae - Phosphate resistant spider mite

One of the bean bean plants grown in the trays is selected in each dish at the time when the primary leaves reach a length of 7 to 8 qIh and are cut off. Small pieces are cut from the infested plant leaves and placed on each leaf of the test plant. This is done 2 hours prior to the treatment so that the spider mites can crawl around the test plant and lay eggs. The size of the pieces of infested leaves is changed so that each leaf of the test plant has about 100 spider mites. When the test composition is applied, the pieces of leaves used for infection are removed and discarded. Plants infested with spider mites are immersed in the test composition for 3 seconds with stirring, then allowed to dry in a fume cupboard and maintained for 2 days, after which the mortality of adult insects is determined on the first leaf. Second

- 192

The results of the experiment are expressed in numbers and letters with the following meanings:

No effect

10 - 25% mortality

26-35% mortality

36-45% mortality

46 - 55% mortality

56 - 65% mortality

66 - 75% mortality

76 - 85% mortality

86 - 99% mortality

100% mortality

R lower ingestion

The results of the tests described above are presented in the following overview.

φ Ρ Φ +4 Μ co 3 Ο 3 Ή Ο. φ Ρ p SW Ο a 3 ο £ 3 φ «5 Ό and q ο η 3 ιτ \

»» W - 3 £ 3 CJ z— > »Φ · e 3 cc ω and co cj φ and p and p - +4 +4 | O « Φ O H q ^ -z <* ·>

193

t — 1 • 3 3 Ό what 2d t> r — 1 3 ε CC and £ 3 • H C and WHAT CC O Ό O ÉH • H 3 Φ ffi 3 H Φ ε + j and and O and Ό O O O Λ O cn r-l

f = and ω Φ and and what x: £ 3 O and what O <a and

α ϋ

4-J χο γΗ χο>

ο a

<η

Φ a

os σ>

1Γ \

Ο οο σ \ σ 'σ \ σ \

AND

I I

1 OJ 1 and and 1 04 / rd > » O £ 3 1 OJ 1 3 m 1 1 and 3 1 b 3 1 O and 3 O and 3 Φ CD 3 and O O 3 and O in. ^ d O £ 3 3 and 3 and 3 1 and CJ 3 £ 1 > 5 O £ 3 O m £ 3 and >> CJ and £ 3 CJ and 1 CJ Ό and and and 3 and £ 3 and rd and 1 Ό 1 > 5 WHAT Ό CJ O t3 •"F and 3 Jid 1 1 3 1 - >> Φ 1 and 3 IO \ ai 3 q- · t n ·. - » >> • rd - ^ -Z Φ and- 1 · * 1 and ’Φ 1

-carbonitril o

O

I • ri · σ>

and-)

AND

CD

O

P

P

O β

CD

P

CD

P

CD

P

O β

And a

P ϋ

Φ

P

C α

4C 't)

JSd

O ia

05 / 3 JC ϋ - >> φ · and β ffl 05 Α ffl ϋ Φ Α β Ρ β Ρ Ρ 1 ο Φ β Α ο Η 3 -

• 3 β

P ίrrσ \ α} p

β ffl

P

Ή β

φ ffl β

φ

Ρ

Α ο

Ρ

Ο α

ω a

α

Α

Ο

Ο a

Α

Α

Ο

Ο ο

and

Α

Α Α Ρ ffl 43 43 Ο A ffl — — — I ffl

Ρ

ΧΟ

Ρ χο β

ffl>

ο

Ρ φ

Ρ σ>

σ \ σ>

σ>

σ \ σ \

Α

Γ- Ο Ο

I I I

AND > 1 γΗ 1 ο rM Ο Α X ο β AND β ι_ι Ο β X “χ β 1 43 1 1 > 5 Ρ f — 1 > 5 <\ Ι Ρ η <Μ Α Ρ Α 1 φ | Ρ 1 κ - "\ β β β β and Ρ Ρ β γΗ Ρ φ Ο Ο β Ο β Ο • Ρ 'μ Ρ ι — 1 ο β Ρ (Ρ β β and 43 43 3 β • Ρ JB φ ο ο Ο υ Η >> β υ <μ 43 β Ρ -Ρ «Μ _Α ο • Ρ β β 43 Ρ Ρ Ρ 43 Ρ ο ffl 1 1 1 β > 5 β 1 Ρ Jri Α Α Α Ρ β ffl ΙΑ 4C 1 —- - Φ Μ Μ Ο m 1 • ri · · * 1 <μ 1 • ri · 1 ι 04 / 1

-3-carbonitrile test substance Aphis Spodoptera eridania Tetranychus Liabrotica fabae urticae undecimpunctata co

X3 'Ko

• a

Β o. Β

m <3β

Ό ε

and a

o o

i — i ε

and a

o o

o ε

and a

o o

rH

Cn cn cn cn cn

I β I I

1 OJ O 3 H rH O β r-i Ή 1 (-1 > 3 1 O .O 1 r ~ J > 3 1 β β OJ β β OJ β β • rH > 3 + -> 1 Φ ω 1 Φ O ÍH and • H ε .Μ ε <β <—1 -P > -. β O β 1 O β -β 1 r-t O β O O β O O th > 3 XJ XI ι — t 1 XI ι — 1 • H r-i β • H - r-i rl ’R4 x: Ό and O (0 Ό O O • H I.E O 1 + J 1 1 β l 1 LO and 1 1 LO O β -P ir\ and *. -of and 1 m · * --of • rH -> •--OF 4- 1 1 1 and Φ 1

pyrrole-3-karboo o

CD P WHAT O • H ω ρ O £ £ and CD P and x O ♦ rH \ £ O oo XI Φ CD Ό • H β O O £ ca

ω £

X o ·

> j φ Cň and £ CD Φ and CD CJ £ and £ -H P + J 1 O

Φ £ (2L) |

«£ CD ♦ rH £ X C- 1 £ £ • rH £ Φ E WHAT and CA CD and i — i £ OJ O 1 P O and rH O X O and ω and

and a

o o

o rH a

«Ω and and • H £ x X O and £ O <4 4h rH

CD

- £ χα

XD c

CQ>

O

P w

Φ p

<r>

ca

OS σ \ σ>

□ λ σ>

σ \

O O o i

and i and n-i and rH i i i

t O P O X 1 CM 1 £ 1 1 1 £ m OJ 1 £ 1 O rH rH CM O rH 1 and £ £ rH O • H 1 rH O and 1 AA O X £ £ and X £ O £ h rH O £ P O CJ £ £ O n X • H > p • H £ • H řo X £ 1 υ X and £ X X and Ή rH rH rH • H 1 X—. O • H 1 X 4-i O • H X • «t rH X X -IN rH 1 • H £ £ 1 £ 1 lA £ £ P IA CM £ £ the CM C * • P > 5 • H ** φ AA - ^ -X Φ 1 and £ . 1 4-i 1 H- 1 <P

-carbonitrile test substance Aphis Spodoptera eridania Tetranychus Diabrotica fnbae urticae undecimpuncteta

CD

Λ

O ip co

Μ Θ φ a p i °

PO ^ - · οΊ c— ε

ρ ρ

o o

f — I ε

p p

o o

o r — l ε

ρ p

o o

ι — I

IT \ t>

σ \ σ \ cr>

crs σ \

I I

I I

1 r-l O 1 r — l 1 r-1 cu > 5 xi 'Ο- > 3 cr \ > 3 1 q q Ι q 1 q q φ cc ÍH φ q <υ O O <ÍH O <P ι — 1 ÍH 1 r — l 1 r — l q x: O m x: LTi x: O O r — l 1 O 1 O r — l • rH SW r — l rH • rl O r — l * rl x: Ό O O • rH q O Ό O 1 1 ÍH q 1 P q 1 1 ir\ ε ÍH +4 n q ro P > 3 Ή q > 3 - - ' in AND Λ β C4 1 p 04 / 1

-4-nitropyrrole ro o

Test substance Aphis Spodoptera eridanio Tetranychus Diabrotica fabae urticae undecimpunctata and:

JZ 'íai

Me o

ir \ • a m o. Φ CL q • S

CL.O' -'OO <3

C

WITH

q.

q.

O

O rH

q.

O

O

O r-i a

O.

q.

o o

r-1 σ>

σ>

σ \ σ>

σ \ ι

ι

AND ΙΓ \ AND rH > 5 C Φ r-H O q q 1 1 rď řo C Φ 1 IN\ 1 q 1 q o Γ ^- i and > 1 and O x: ο q O. O 1 r-1 O 1 q O O q irs x: Ή M · SW <—1 q xs 1 O Ό 1 • rH • p • H O r “i • H 1 x — p Ό O Ή X) q O Ό H 1 1 C 1 -q q 1 · * >> m O. 1 oo • H q OO ΠΊ C - ___ • Ί · ·. C > 5 Φ OJ 1 1 OJ 1 O. OJ 1

-nitropyrrol

what CD O • Ρ Ρ 3 Ρ ο β 3 and 3 * Ρ β -β ο β • Ρ ο £> φ Μ . cO τΟ • Η β Ο Q 3 ΙΑ

- 03 / 3 χ: ο S φ · β β 3 «and 3 ο φ and β · Ρ β Ρ Ρ 1 Ο φ β and ο Η 3- ^ η

α • Η • 3 β

Τ3

C-

199

Ό • Ρ β

Φ β

φ ρ

Λ

Ο

Ό

Ο

Ο.

ω β

Λ

CU

Ο

Ι ι — Ι a

ο ο

ο β

a <η φ a • Η <0 33 0 and 3 ο << Η <ρ α

Ρ

XD

CoΑ What σ>

σ \ σ \ co

I • Η

Ό

AND

ΙΑ

I ο

β

Ρ

Ό

β Ο Μ- 1 3 β Ι m > χ> ι (Ρ ο 1 ιΡ β Ο Ρ and ο β Μ - ' β ιΡ β Φ ι Φ £ 2 > 5 Ρ <Μ <Ρ Ο and

σ \ σ>

σ \ σ \

Γ ”)

I ρ ·

I β

ο ιΡ

Λ

Ο τΗ

Ό η

OJ ι

ΙΑ

AND

Ο β

ρ • ρ β

AND

-trifluoro-p-tolyl) 200

Example 67

Insecticidal activity tests

Haliothis virescans - 3 · instar

The cotyledons of cotton are immersed in the test composition and allowed to dry in a fume hood. After drying, each leaf is cut into quarters, which are individually placed in 30 ml plastic medical bowls containing a 5 to 7 ml long moistened dental swab. One bead (3rd instar) of the gray is then placed in each dish and the dish is covered with a lepenkoym lid. After 3 days, mortality and a decrease in consumption are found.

Empoasca abrupta (adults)

The bean leaf, about 5 cm long, is immersed in the test composition for 3 seconds with stirring and then allowed to dry in a fume cupboard.

The leaf is placed in a petri dish (ICO x 10 mm) with damp filter paper at the bottom, into each

Ten adult Empoasca abrupta adults were plated in 201 dishes and allowed to run for 3 days. After this time, mortality is detected ·

Blatella germanica - Adult Male (bait test)

Ha 1 g of corn flour, presented in a wide-necked flask of 30 ml volume, Senipipets 1 ml of a 1000 ppm test compound solution to prepare a 0.1% bait composition. Bait v

was dried by placing a gentle stream of air into the flask and then placed in a 1 liter wide-necked flask in which 10 adult male Russian domestic animals were placed. The bottle is covered with a mesh lid on which a piece of cotton soaked with 10% honey is placed. Mortality was found after 3 days.

Blatella germanica (male) - adult male (residual effect test)

Pipette 1 ml of 1000 ppm acetone solution of the test substance slowly onto the bottom of the Petri dish (150 x 15 mm) so that the bottom of the dish is202 as evenly as possible. Mortality is calculated after 3 days.

Spodoptera eridania (larvae 3 · inatar) - systemic efficacy

The test compound is made into an emulsion containing 0.1 g test substance, 0.2 g emulsifier (Emulphor EL-620), 10 ml acetone and 90 ml water. This composition is diluted with ten times the amount of water to give a 100 ppm emulsion.

This emulsion is further diluted 10-fold with water as needed. Bean bean plants whose primary leaves have already reached a length of 7 to 8 cm shall be cut at least 3 cm above the soil surface to prevent contamination by soil bacteria that could cause the stem to warm up during the test. The stalks of the cut plants are placed in the test emulsions and each stalk is wrapped with a piece of cotton wool which keeps the stalk at a certain distance above the bottom of the bottle while preventing evaporation and volatilization of the test substance. This arrangement is kept at 27 ° C for 3 days to allow the plant to take the active substance, then one leaf is removed from the plant and placed in a Petri dish (100 x 10 mm) with 10 specimens of Spodoptera eridania larvae. After 3 and 5 days, mortality and a detrimental effect on the magnitude of the diet are found.

Empoasca abrupta (leaf) - adults (systemic effect)

The test compound is made into an emulsion consisting of 0.1 g of active ingredient, 0.2 g of emulsifier (Emulphor FL-620), 10 ml of acetone and 90 ml of water. This composition is diluted with ten times the amount of water to give a 100 ppm emulsion. This emulsion is further diluted 10-fold with water as needed. Bean bean plants whose primary leaves have already reached a length of 7 to 8 cm are cut off at least 3 cm above the soil surface to prevent contamination with soil bacteria that could cause stem rot to rot during the test. The stalks of the cut plants are placed in the test emulsions and each stalk is wrapped with a piece of cotton wool that keeps the stalk at a certain distance above the bottom of the bottle while preventing evaporation and volatilization of the active ingredient. This arrangement is left at 27 [deg.] C. for 3 days to allow the plant to take the active ingredient, then one leaf is removed from the plant and placed in a Petri dish (100 * 10 cm) with about 10 specimens of Fmpoasca abrupta adults. Mortality was found after 3 days.

The results of these tests are expressed using the same scale as in Example 66.

The results are summarized in Table II below.

) β

ft ft

Hc A XO

M Ό AG • AGO tS) · Α O Φ xj O A '3 A ft o

P3

C what c

>

xo β

β ft ft

o o

A ft test substance EA HV systemic effect <c

M β

ft ft

O o

AND

OX fl ft

W ft ω o

o rH s

ft ft β

and a

o o

O

A β

ft ft o

o rd

OX ox ft

Ox ox

OX ox

AND

I I

1 1 ro 1 1 , -1 1 1 AND OJ AND 1 OJ AND rA O OJ > 1 1 O AND AND 1 O > 5 X 1 G AND e — l O •AND AND β β AND AND Φ O x AND AND O 1—1 0) cc O AND r-i O AND AND rA «Η AND Jxi 1—1 AND X •AND >> •AND SW • rH 1 X O O X ft β (J AND ro O AND • rH 1 X— \ O • rH AND X 1. t — 1 • rH X Ό Xt H XI X --of O τΙ • rH XJ O 1 > 5 AND 1 1 X AND AND 1 irx ro β WHAT trx ft AND AND -P lf \ O •with φ J «J 1_1 Φ >> ♦ rH · * - ' 1 AND 1 1 β ft 1

pyrrole-3-carboq k a xn cx m cx Ό Φ • P 3 O N -P O ω xj O

q '3 pH Ο CQ ε C cx Ό cx WHAT q O > O xa O q ι — 1 Λί ω 8 q cx • Ρ cx XJ < Χ3 w O O '> 3 i — 1 Φ Ρ ε ε cx φ cx -Ρ w cn ω O > 5 O cn r-l

σχ σχ co

CM ε

cx a

o o

H cr * σχ

CX cx o

o o

i — I ε

cx cx o

σχ σχ σχ

CD ϋ

P x and x and q

ca>

o ρ

ω φ

ρ

1 O H of-" | rP r — 1 1 3 O r — 1 rP O O • p 04 / r-l q • p 1 > 3 XI q q 1 <P q q CM q q 1 q P q • rl > 5 P 1 φ what 1 trx > 5 • H O q cx • P ε <H ε cx q r-1 P x- * x q O q 1 O •in q O X3 1 rH O q O n q 1 O X> O and > 3 X> rP 1 x> X—. r-l q • P - r-l q • p XJ rP 1 r-1 -C ca Ό and O (0 Ό O O cx > 5 Φ 1 P 1 1 q -__ ' C • r4 1 LCX and 1 1 IfX O q 1 Φ Ό m cx m Λ > 3 CM <P 1 1 M- 1 1 1 -in 1 cx

q ρ

C

Β β XO O 3 M CX Ό 4) • H C O N -rt O dxjO fi X3 iP

O

CQ

WHAT

Ό

CO c

>

xo c

s a

and o

o o

iP os test substance EA HV systemic effect

o \ a

and a

o o

e a

and o

o r — I ε

and a

o o

o ip ε

and a

o o

tp

OS

Os os

Os

Os os

Os

AND

I fi I

1 C \ l 1 r ™ Í > 3 fi Φ 1 O £> fi WHAT 1 CSJ 1 O 3 r— < <P • p iP O fi fi > 3 rH • H fi P 1 OJ 1 fi 1 fi O iP 1 (p O with <p Jbd ε fi and ♦ H O fi fi O fi 1 O P WITH-* C (P O fi fi O n fi 1 fp O .fi »RH > 3 rP 1 £> and > 3 £> O Ό and Ή Λ ι — 1 rP • H fP fi »RH 1 X — S T3 O O Ή Ό and O WHAT Ό r-1 1 1 fi fi 1 P l > 3 bunch and fi P irs and 1 1 vfS Csl fi > 3 • rH # » and 0) 1 and fi M 1 1 1 P · 1 <P

-3-carbonitrile

Μ β

rH S ΧΟ ΟΧ 3 ΟΧ ω ω • η co Ν · Η ο ω XJ ο axoH ·

Ο

CM

CQ

Ό β

>

χβ c

οχ

ΟΧ ο

ο ο

rH

Λί φ WITH β οχ • rH οχ XJ <! '3 W ο ο '> ϊ Λί ο Η • Η θ E οχ φ W οχ • ρ ω 03 / ο >> ο 03 / rH

σ>

οο

With οχ οχ ο

ο <T>

LO

♦ ->

χο

ΧΟ β

>

Ο

Ρ ω

χ>

<τ>

I σ \

1 1 and γΗ 1 · Η ι CM rH > 5 ο χθ ► Μ · CD ο γΗ X AND β β 1 1 ι — Ι Ο Ρ and Φ 03 / β and X X Ή ο 4 «ί Ο ο Φ X β ι — 1 β 1 rH and T “t > 3 ο χ Ο m X £> Ό οχ χι α rH ι Φ • rH 1 χ- ^ X Ή χ: rH γΗ • rH Ό • 'ί · rH 03 / Ό φ Ο • Η Ό 1 > 5 ϋ 1 ι β β 1 l £ X CM C ! ΙΓ> and β + J m X. Φ η · * ._X > 5 • Η Μ · 1 ι Μ · 1 ΟΧ β CM

-nitro-5-phenyl-I and xo cx

CX

TO <U • H β O N -P O OJ XJ O β '3

O

CQ

WHAT

TO what β

>

XO β

CX o

O

O i-1 Test substance EA HV Systemic effect a

CX ft <5 and O o <—i a

cn a

and

CX o

o r-l a

cx cx o

o a

cx cx o

o o

H a

cx cx o

o ox x ox ox x ax co β CO

Φ o

O -P

W β <υ co β s • Ρ β> Φαί • Ρ X5 -Ρ o • ρ cx ox αχ trx xo cn ox

OX cn ox

I o

β p

• Η

I cx

I β

O

QJ

X

AND

Es

CD

-P

CX β

XJ β

β o

co β

o cx a

and

AND

Spodoptera eridania - Blatella.

1 1 β 3 < 1 1 O rP m 1 ιΡ and irx β β > 5 1 Μ- <Ρ Η 1 O P β β I — 1 Ι • Ρ Ο β i — 1 • rM here C O β β β O x: β <P .-P β ο -Ρ β i — 1 O 1 and P β (Ρ 1 > 1 ·· YEAH • P ’Φ O O > 5 SW 3 CX β O IT 1 β • p cx υ X— ~ Xd • rH 1 X—- rp XJ IT O * Ρ 3 ι — 1 WITH nO rp O 1 1 β τθ Μ > χ ΧΕ AND > 1 β cx LCX • P 1 3 ιΡ β n n β β '- • P m IN ο C4 QJ > 5 1 • xt β ιτχ Ρ Ο C \ l 1 CX (XJ 1 1 04 / 1 1 (X

I a

cn

- 213 puts the results of another high-capacity screening program.

The compounds are dissolved in acetone and the solutions are diluted with equal volumes of water. The final concentration of each compound in the test mixture is 150 ppm. The test material is transferred to a single well in a sterile 96-well tissue culture plate (COSTAR) using a micropipette (25 µL) and the solvent allowed to evaporate. The plates thus treated are either used immediately or stored in the freezer without appreciable harm to the active compounds.

50 µg of freshly prepared C. elegans in CbMM was added to each well of the drug and several control wells on each plate with a micropipette and incubated at 20 ° C.

After 4, 24 and 48 hours, the efficiency is evaluated under a scanning microscope. Immediately before reading, the plate is slightly tapped to stimulate worm movement. Activity is assessed subjectively but emvantitatively, based on the effects tested by ala <

215 • dosing of C. elegans (25 to 100 µl) into wells with test substance ♦ observation of activity after 4 hours day 5. Observation of activity day 6. Observation of activity

Note: \ ^and 'wells with the test substance may be prepared either immediately or in advance and stored in a freezer

The data obtained in this test are summarized in the following Table III.

B) Activity test against Meloidogyne incognita

Meloidogyne incognita nematode populations are maintained on greenhouse-grown tomatoes (Pireball). The eggs are removed from the roots of the contaminated plants and are laid for 24 hours on moist filter paper. Hatched larvae invade the water under the filter paper. For the test, the larvae are transferred to wells in plates containing test compounds deposited there in the form of a 3% acetone flow. 300 ppm · Approximately 10 larvae are introduced into each well. Mortality was observed after 24 hours, when the infected well plates were maintained at 27 ° C.

The data obtained in this test, expressed on the same scale as in the previous examples, are summarized in the following Table III.

- 217 Table III test substance

C. elegans 150 ppm larvae adults

Meloidogyne incognita

300 ppm

4,5-dichloro-2- [p- (trifluoromethoxy) phenyl] pyrrole-3-carbonitrile

4.5- dichloro-2- (a, a, a- 9)

(trifluoro-p-tolyl) pyrrole-3-carbonitrile

4.5- dibromo-2 - ((x, <x, a- 9 9

(trifluoro-p-tolyl) pyrrole-3-carbonitrile

2,3-dichloro-4-ol

-nitro-5-phenylpyrrole

218 test substance

C. elegans 150 ppm larvae adults

Meloidogyne incognita

300 ppm

2.3-dichloro-5- (p-9 9)

(chlorophenyl) -4-nitropyrrole

2,3-dichloro-5- (3,4- 9 9)

(dichlorophenyl) -4-nitropyrrole

2- (p-bromophenyl) -4,5-9 9

di-chloro-3-nitropyrrole

2.3-Dichloro-4-nitro-9 9

-5- (α, α, α-trifluoro-p-tolyl) pyrrole

219

Example 69

Using the procedures described in Examples 66 and 67, the activity of the compounds of the invention is evaluated against various insect species, including Empoasca abrupta (EA), Heliothis virescens (HV), Spodoptera eridania (SE) and Blatella germanica (BG). The results are expressed using the same scale as in the previous examples. The results are shown in Table IV below. When two or more assays were performed with the same compound, averages were calculated from the results. A dash indicates that the test was not performed in the present case.

c η a χο a a

L Φ • rl β.

N · Η O Φ XJ O β '3 rP effect

with

Φ w ρ ω

W »»

«A

and a

o o

r — I a

and a

o o

r — I cn cn cn <§

> M 3 ω O O r — 1 1 WHAT and O and and OJ OJ f — 1 O

O

I 3 O i — 1

X ω

Eh a

and a

o o

oo cn cn co

what P 1 in 1 m 1 'what 1 í — 1 r-i β O O β XD 1—1 β β X! > 3 what O and > • rl I — 1 O Ό > 3 P t β 03 / LO Φ Φ r 4-t P OJ 1

<n <n tn i

r-f

r— ( 1 IN· > 3 β • rH 1 Φ β and «Ρι Ρ ο | • Η β ΙΟ β X 1 ο • rl ο ι — 1 χι Ό β ο β 1 Ρ β C0 ΟΊ Ρ β β ^ 3 1 04 / 1 and

cn cn

OJ cn

4-chloro-2- (p-chlorophenyl) pyrrole q

H B

XD P a

Q Φ • q ta--j j j j j x x x x3 r — i a>

q t-l

XJ '2 <β

M

I

O a

p p

o o

CM

CM and p

Φ P

P w w cn o >> o

W r — l <3 q

Ό ux σ \

W cn a

p p

o o

H

Θ

P

P o

o o

t-1 a

p p

o o

H

OA cr>

σ \ οχ σ \ οχ a

p p

o o

o r-l a

ρ p

οχ οχ

O O r-l O O σ » 1 rP 1 1 p- 1 O q - 1 O q O WHAT t — l 03 / —X q rH 1 '- · 1 Jd 1 řo rP XJ what 1 · - '' Ρ CM P • rl CJ 1 CM r-l XO 1 q 1 rP t — l 1 > 3 Η q r — 1 P P O • rl q q O řo • rl - · q q O 0) XO rp q q 1 q P r-l <P q XJ 4) O CM > 1 • rl r-. q what O <Fri x> 1 P q CJ O > • rl q q and r—- O • rl r — l O Ό O what O r — l X) Ό XJ P 1 t — l q řo q 1 CJ m ux x: 1 x> q what UX • rl φ O WHAT 1 ω Jd - Ό P 1 1 ux <P 1 M- 1

- (ethoxymethyl) pyrox d and 3 id a

O Ό Φ

CQ-p co N -P o Φ XJ o β '3 H

id Φ β β and • rM and XJ X3 M O O t — 1 id O β • rl and E and Φ w P w O w O > 5 r-1 ia

«3 β Ό 1 t- β and and w cn o O i — i β and CXJ cxj and O OJ O 1 O rH

co id

P

XD xo β

>

O

P ω

φ

P

CA

CA

Ox ox ox

OX co

K p · ox οχ

CA

OX

1 P and 1 1 XO * 1 r-l 1 CXJ O 1 rp 1 β 1 N CM 1 rp O iP β 1 1 O rp rP O Φ CXJ β r — 1 β • P YEAH β YEAH 1 O > 5 β β O β <P β ι — 1 β > i P • P >> O YEAH Φ and • P Ό and x: β O Sh rP β 1 β P J3 • p β >> O ia 3 Φ • H Ό O YEAH 3) > » WITH Ό 1 rp P β p- ϋ ρ — X 1 ia YEAH Φ 3 AND rH LA O β id 1 r-ι >> - p- 1 1 1 and 1 1 p-

- (3,4-dichlorophenyl) ββ

Η φ • η co Ν -Η Ο

φ xj ο β Χ = 1 β Φ ε β and Ή and χυ <3 '3 Μ ο ο β Ο ε • Η and ε and φ W • Ρ ω ο η ο >> β m

• 3 β

Ό

C6 a

and

W Ο ω ο ι — ι a

and

Λ

Ο

Μ- — — I ι ε

CU> ^α ο

ο β

ε a

CU ο

ο ο

<jJ - —a

ο ο

β

ΟΧ σχ σχ αχ σχ σχ σχ ο

ι ν

- I σχ σχ ra

Οο σχ σχ σχ σχ σχ σχ β

Js!

β

ΧΟ

ΧΟ β

α>

ο

Ρ σι φ

β

β) rH 1 1 1 η ι 04 / rH rH 1 > 5 Ο rH β β β • β Ο φ β β rH <Ρ > 5 Ρ £ 3 β and • β O ο rH β • rH rH Ο Ό £ 3 £ 3 £ 1 1 Ο β β ιοχ • rH φ β Μ Τ3 ε Λ!

Μ · I I I ι

1 and rH > 5 1 ι β η 04 / Ο ι 1 «Η β β β β ο • β Ο 3 β β (β Μ β β £ 3 γΗ > 5 β Ο > 5 and β • β £ 3 r — χ ο Ό β β £ 1 1 Φ > 5 β IÍX ε β C0 Μ Φ Λί β- AND <β 1

ι β I? >> β £ 3 Ο β 3

Ε Η ε <ρ

I · β β β

I β ε ι ο Β β & a • η

Ό 8

AND

ΙΓΧ I ~ 04 and Λί

-ν ι I I

-tolyl) pyrrole-3XH β

η a

XO CL a

J Φ βθ Ν -Η Ο φ xj ο q * β γΗ

ϋ φ and β CL • rM CL χυ <5 Χ3 W ο ο 3> 3 ϋ Η Ο and • μ CL and W CL φ -μ C0 ο η ο >> η ι-1

• β β Ό « t- and CL CL O W O 1 1 “1 and CL CL O O ΙΓΧ O r · 1 (XJ OJ 1 and > CL CL O O rH and CL CL O O O H and CL CL O O r ~ 1

φ ϋ

μ

Ό γΗ

ΧΟ β

Φ>

Ο μ

<ο φ

μ σχ σχ

ΟΧ σχ σχ σχ

Ο

1 1 CL 1 rH O q q >> rH (XJ CL «Μ 1 q q rH -μ O >> • μ r-1 β β x: Φ O O X) • μ q q Ό O φ 1 β ϋ ΙΓΧ ι — 1 ι <> H 1 AFTER IN 1

ιτχ xfιτχ

In σχ σχ σχ σχ σχ σχ σχ σχ σχ σχ ι ι

xř q rH řo • H 1 AFTER CL q CL μ 1 rH • μ 1 1 CXJ řo β CXJ 1 β O 1 rH and φ X3 and > 3 O <ÍH q O β q q φ q Φ x> O ϋ x> • μ β | • tH q Ό (-) AFTER Ό O 1 1 1 β irx • H rH irx rH Ό O 1 q • xt 1

pyrrole-3-carbonyl 3 3 id Α ρ Φ Ρ CO Ρ Ο

Φ xj Ο βΡ Ρ

id φ ε β Α Ρ Α XJ Ρ W ο ο S >> id Ρ ο ε Ρ Α ε Μ Α φ Ρ ω Ο η Ο >> η Ρ

σ \ σ \

Α • ri ·

A Α • ri * -ri Α • ri · σ \ σ>

Ά

Α

I • 3 β

Ρ

CS

Α

Α

W Ο

ο) ο

Ρ

WITH

Α

Α

Ο

Ο ο

ε

Α £ ° * ο ο γΗ ε

Α

Α

Ο

Ο ο

Ρ ε

Α

Α ο

ο

Ρ νο ο— α α α φ

id

Ρ

Ό

Ρ

Ρ β

ω>

ο

Ρ <η φ

ρ

ο ο α 1 1 1 ε 1 Ρ Ρ ο β ο 1 Ο β ο 1 β Α β 43 3 Α β —- β Ρ Ρ - > » ι — 1 1 > 5 Ρ Ρ <μ 1 Α Ρ 04 / Α Ρ AND Ρ 04 / β 1 -—- β Α β 1 ι — 1 Ρ β ι — 1 Ρ Ρ ε >> Ρ Ο > 3 Ρ • ri · 1 ο β β Ρ β β 1 3 β φ ο r * φ ο ι — ί · * 43 «Η 43 Ο <Η 43 > 3 3 Ρ Ο β • Ρ Ο β Ν Ρ β (0 Ρ β φ β 3 1 Ρ id 1 Ρ id Φ —- Α Ρ 1 Α • Η 1 43 1 - β Ρ ** β Ρ 1 04 / • ri- 1 1 ri ^- • ι 1 Ρ 1

-tolyl) pyrrole-3 £ μ and x ω x CO Ν X Ο KJ Ο £ Χ X

ΙΑ

0 and β and X and x> X W O O * >> AA X O and X and and and 0 W X ω O « O >> n X

AND

C-

CM

CM

I · £ β

X ta a

and w o ω o rH a

and a

o o

O

X

CA

CA

CA <A

CA a

and a

o o

ca a

and o

o o

CA

CM

CA a

and a

o o

x

AND

I X I

CQ and O £ 1 and X 1 1 and 1 £ X >> m x-x XD CM > » X 1 β 1 1 1 and £ CM O X X CM £ Z — S X | O X AND Xfl O X X and X £ £ and C X β O £ £ X O > 4 CQ XJ β O £ w >> • rH £ > 0 O YEAH X X and β SA O • rH «Η £ X > 5 | —1 O X • P X β WHAT X SA X .Ω X 03 / 1 WHAT AA 1 X > » £ 1 Φ LA > » 1 LA 0 β £ LA -P - AA m and 0 Jd * » H 1 1 H '-X 4h 1 H-

-chlorophenyl) pyrrole3 X ft X Φ χ co N X O Φ xo o ΑΧ X σχ test substance EA HV SE systemic effect and

A ft o

O

X β

ft ft o

O

X • 3

G

X β

A ft

O

O

X β

ft ft o

o o

X β

ft ft o

ft

O

O o

X β

ft ft o

O

X οχ

Ox ox ox ox

OX

OX irx

OX

C— OX

O C- ox 1 1 AND AND O 1 O 1 3 •"and- X 1 O 1 X 1 1 1 X Φ X AND She knows ro ro X - ' O AND AND Φ • H 1 · .— 1 O 1 •AND AND ffi fi AND 1—1 1 ***. X ro X O X 1 AND O CXJ X X 1 1 i — 1 1 X 1 AND 1 ř> » AND X r-H irx X ro 1 and AND AND G X O • rH CJ 1 AND > 3 O Φ AND $, AND • rH X C and ft X AND r— AND IN-' 1 X O X AND-·, X AND AND > 3 • rH X 1 AND c ~ * and rH O O Φ ft C > 3 Ά AND CJ > 3 • rH X fi ι — 1 O X - > 3 AND-( •AND 1 X X X X X) AND ro ft • rH X CJ O 1 O 1 > 3 <LÍ -__ - 1 1 AND LCX • r-t CM X cc β 1 X irx X 1 X A_J AND 1 CXJ > 3 • rH Λ ϊή ft 1 1 Φ 1 X 1 G C AND· <- 1

-carbonitrile σ \

CD

C4 β

ο.

ρ.

Ε ε: η

XSJ

Όί Ό 0) • ΗβΟ Μ - Η φ χυ ο Ρ'Ρ Η

Φ Β β Ρ. Ο. κ_> <Ό W Ο ο * >> Η Λ) ο β • Η Ο. Β ο. Φ W - W ο η ο > 5 Γ-1 «

<3 β

Ό

C— ε

Ρ.

Ρ.

W ο ω ο

Η ε

α

Λ

Ο

Ο ο

ε

Ρ.

ρ.

ο ο γ “I σ>

σ \ σ \ σ \ σ -.

σ \ σ \ <τ>

σ '.

σ>

σ '»σ \ σ \ σ \ σ \

Μ ε

ρ.

Ρ.

ο ο

ο γΜ ε

Ρ.

Ρ.

ο ο

γΗ

\Ί \ σ \ ιχ \

Λ

Cd κΟ ω

+ J

Ό χα

C φ

>

ο μ

η <υ

-μ ι

xf I

1 · * 1 xf ι CD AND η Η 1 CD 1 1 ι 1 **> 1 X ρ r4 ο 1 ι-Η Ρ r-t ο χ> ΙΓ » Η > » ο >> ι — f Ρ Ρ 1 χ: ι — 1 r — 1 β X! φ ο Ρ β -Ρ Ο XJ φ ο <ρ ϋ ο Ο Φ Ρ ο «Η 1 Ρ AND γΗ <Ρ Β Ρ 1 Et ο η χ: Ρ >> > 1 ιτ \ Ο 1 f — 1 ι α Ο Ρ. 1 γΗ ε χ: r-l ι — 1 • Η r — 1 ο ο Β χ; ο υ Ο * Η Ό XI X! Ρ ο ο β. ι Ρ. Ρ 1 υ £> • Ρ Ρ ι χ> ο. Ρ + J ΓΟ • Η Φ • Η χι Ρ. AND • Η · » T3 β 1 ΙΓ \ 1 Ρ, β CD 1 1 1 xf AND

pyrrole-3-carboi

P q

ρ and x and cx

I CX X Φ ρ what N P O Φ xj O qx ρ test substance EA HV SE systemic effect

-Her

M

C \ l σχ a

cx cx o

o ε

cx cx o

o r-1 • 3 q

X cε cx cx o

o ι — I ε

cx cx o

o o

r-l ε

cx

CX ο

ο

Ρ ε

cx

CX ο

ο ο

ι — I ε

cx

CX ο

ο

Ρ ox σχ trx irx σχ σχ σχ σχ σχ σχ σχ ρ · σχ σχ σχ σχ σχ σχ σχ ο. σχ ι

AND 1 Ρ 1 ο ι q ο ι 1 CM 1 cx 1 q i Ρ Ρ q γΗ q Ρ O P X Ό q Ρ X ο 1 Ό2 1 P 3 1 1 1 > 3 Ρ φ Ρ q Ρ Ρ > 3 P P ΙΓΧ ρ- cx q • γΗ X ω φ 1 X P O Ρ X φ φ q P P q ρ- ρ Ρ • Ρ 1 · «—1 I CC O Φ q q AND > 3 q Ρ X 1 1 P ε P > 3 ι — 1 ι q ο - 1 Ρ- Ρ X > 3 1 cx > 3 CM φ χ CM ρ · 1 1 Φ X and Ν ι «Η q 1 Ρ • P O P q q q ω I — 1 Ρ Ρ Ο X X and > 3 φ ο ο I > 3 ___ > 3 q 1 P - P X ρ Ρ 1 X 1 q q IfX Φ and O AND £ η Ρ ICX φ >. - - · P Ρ φ Φ ι φ 1 Ρ cx P 1 1 1

-carbonitril /

a a a xd and 3.sd a o ό ω «and CO n a o

Φ xj O 3X3 H Jd Φ and 3 and and and XJ Ό w o o £ and O ε and and ε and φ M and cn o n O řo « and

co uo what co what • 3 ε

and a

w o cn o a

ε a

and o

o o

what what what

OX

OO whats what

OJ

I e

and a

o o

and uo

Λ what what

ΟΊ what

2d a

xd rd

XD

CD>

O a

<n φ

and what about what

and a

o o

oo

AND

1 and Ό 1 l and O 3 3 rd • td 3 and • rd 1 Λ m 1 1 and 1 and O 3 3 >> and rd 1 and 1 and O 3 3 > 5 -M- > 5 3 CM and of-\ • rd 1 and · » and O 1 > 5 and 3 m with-' and> X » 3 3 > 5 and 1 and and 3 O Φ 3 and ε ři l řo WHAT and 34 • a 3 O 3 i £ 0 3 Jd Λ 3 and O 3 φ 1 Φ • rd CJ O O £ 5 YEAH with 3 » τ) • rd and 3 3 and 3 O 3 1 £ 3 and CD Ό O 3 O | CJ 1 Jd 1 r-1 I and * » Lf \ and CM 1 LOi J3 1 x: OJ «· Ό m · " CJ m CJ 1 1 1 1 Φ 1

ri a

and o

J =>

what

AND

CM

AND

Sd fi h a xo and m a fi <0 -fi 3 0 N -rl O Φ XJ O fi fi rd

Φ and fi and • fi and XJ < fi W O O *> 3 rd O and • rl and and and φ W P W O m O > 3 rd 03 /

fi fi fi

Os

Os

Os bunch crs

OS a

and a

o o

pers

OS

Os

I drawbar (fi

OJ

I a

and a

o o

o rd a

and a

o o

rd os os

OS axis a

and a

o o

o rd a

and a

o o

rd os

Os co

Λ2

P xo rd

XO fi co>

O

P <n φ

p

Ο- O 1 rd 1 řš M C Ι »· 1 Φ 1 fi CSJ rd fi <P O O 1 • ri O fi fi rd rd fi r-i O fi fi O P fi rd what O fi • ri CJ fi Jd • rl fi C 1 CJ 1 fi > 3 O Μ- • rd (fi 1 and fi Ι fi 1 fi- fi and 1 rd rd CD O M- O n > 3 4> S fi - fi - ¹ C • rl fi (fi fi 1 Φ fi 1 - > 3 irs 1 irs 1 and

• ri fi

P • H fi

I pers

I a

o fi fi • H fi

I irs> 3 fi φ

fi o

rd fi

O

I a

and

-1-methylpyrrolf

P β

p and XU CL 3 ϋ CL X) 4)

Ρ CO Ν P O Φ xj O βΌ P

-M Φ and β Ο- • rH Ο. XJ <Ό W O O Xm rH O and • rl CL and, CL φ M P co O 03 / O > 5 rH 03 /

ox ox <3β

Ό es

O- O- O what O rH and O. O. O O | O rH with m O. CD ο- 1 ο

o rH <4

W a

oοο o

o rH

O.

ΟΟ o

rH

OX ox

From ox ox ox ox

OX ox ox (JX Ox cO)

P

XD xo β

co>

O

P

Φ

P

I rH I

> 3 • H β X φ 1 r-1 <+ H M- • r4 1 ·. β LTX m P 1 1 and P β O O O β β X X β β t > 3 O CD O. il

O CI rH rn

X

I Ρ I lil

φ ο β ο Ο > 3 and X Ο β X β β β Ρ Ρ β Φ O C0 X • Η CD <% H 3 ϋ ο β ϋ 1 rH 1 Ρ 1 1 CD «Η m Ό ΙΓΧ m 1 Ρ AND 1 1 ι and β rH Ρ ρ- r- Ρ O Ρ Ο Ρ Μ Ρ ο β —- β β m > 3 β X 1 β Ρ ra- » β β 1 trx > 3 Ρ AND φ > 3 ^ · 1 Ο. β CD ^ Η Ο-

nitrile

XO Α 3. Μ ω • Η β β Η Η Η> Ο βΧ3 Η σ \

AND

- ^ m

AND

Λ4 Φ β β Α • Ρ Α ΧΟ <ί Χ3 Μ Ο 5> 5 Ο γ4 Μ ϋ β • Η Α β Α Φ Μ -Ρ W Ο 0) Ο >> ι — 1 η

<3 β

Ό ο &

Α

Α μ ο ω ο

Γ ~ 1 a

Α

Α ο

ο ο

ι ^- 1 β

Α

Α

Ο

Ο γ4

ο) σ '

σ.

Ολ

σ.

σ.

ΙΓ \ σ \ σ>

σ.

σ '• αί

Μ β

Α

Α

Γ Ο γ-I β

Α

Α

Ο

Ο

LÍX

σ.

θ 'σ

Λί

AND

ΙΓ \

AND

Ρ AND χ-χ <* Ί m ΧΟ ^ τ ι — 1 1 AND ι γ4 >> γ4 γ4 ΙΓ \ r4 η β Ο Ή 1 Ο ΧΟ φ Ρ Ρ β Ρ β ! «Η β Ρ ο ρ ffl 04 / Ρ >> • Η Ρ >> > 1 Ο Α β χ> Α Ο β γ4 Ο Ο ♦ Η γ4 Ρ Ο £ ί Ρ χ> Ό >> η ρ ϋ Ρ Ρ | β φ X) Ή • Ρ ffl Μ · Φ • Ρ 1 Ό β Λ1 μ <Η • Ί · 1 1 AND 04 / 1

• ρ ρ

Ρ • Ρ β

Ο

Χ>

f-t ffl

Λί

AND

AND

Ρ ο

ι-1 Χ3 ο • Η

Ό

I χίπ

Phenyl) -4,5-diiodo3 M CX Ό tu Ρ θθ Φ XJ ο X3H

Φ and β CX • P CX XJ '3 and O O * >> i — 1 O and • P CX and CX 0) and P cn O 0) O > 5 i — 1 n

• 3 β

M ιτχ m

OJ ι

and cx

CX «O cn o r — I a

CX cx o

o o

iP a

cx cx o

«σ σχ ιτχ σχ σχ σχ σχ σχ

Σχ σχ co σχ σχ σχ ο and cx cx o

o o

rJ a

cx cx o

o (P

P- 00 β

and ρ

XD ip xfl β

β>

O

P

CQ

0)

P o O

I I

1 1 p- 1 O β YEAH 1 OF** rH cx 1 of-. • P r-l tP IT β 1 1 > 3 1 Φ 1 irx YEAH r-l m <H P 1 cM P O « β O 1 ε > 5 Φ β CJ O β and O C and β 1 «Ρ β O β ω > 5 rP YEAH YEAH «Η X CX >> O CX & • P p O O 1 O • H Ό O X β β cx β Ό 1 rP P P Φ P 1 m x: Φ • P YEAH 1 • P m O β 1 irx β ** CJ 1 1 1 (P 1 1 04 /

- (p-chlorophenyl) -1-methyl-4-nitro

Μ β

η and χο a

3Μ α -σ η β ο ν -ρ ο

φ x> o β * 3Η • M Φ and β and • P λ X) · < X3 w o O S> 3 (P O and • P and and and φ W P ω o 03 / O řn iP 03 /

and and w O what O ip and and and 1 O O WHAT O m rH CM

Ε a

and ο

ο ι — 1 <η <η cn cn cn cn cn cn cn cn cn cn cn cn

and a

o o

o p

and a

o o

I — i cn cn cn cn co ϋ

P xo rp xo β

CD>

O

P oa a;

ρ

I >>

cn i

^ 3

X i o

and 1 O X P 1 rP -P CM φ rP β 1 and O P and β β • P O O β β β 3 ^ 3 O X rp and X • H <P r — i β τι • P (P (0 1 β > 3 urx P β and • S — ✓ Φ m 't 1 1

1 CM 1 z — p. rH X P Φ and 1 Ip > 3 β 1 1 X O iP rH β P 3 O • rH O Φ rP β β rP and β P X > 3 • H > 3 • H CJ X β and β • P O P r — i O Ό X v-z ip X AND P 1 > 3 β tn Φ and β CD t_1 Φ 5í 1 1 tH 1

- (p-chlorophenyl) tn and β

XP β Ρ XD 3id and Ό 3 Ρ β O H PO 3 xj O β * 3 P

id 3 β β and P and xj <5 -3 W O O Sp P id O β • rl and β and 3 W ρ ω O 3 O >> P 3

CA ox ox

I orp

OJ

I • 3 β

Π3 tβ a

and w o ω o i — l β

and a

o o

O

P

CA

CA

CA

CA

OX

CA ox ox

OX

Pj w

id

P

XD

P

XD β

>

O

P m

p β

and a

o o

i — l β

and a

o o

o rP β

and a

o o

P ox

AND

1 • H Ό 1 1 • H β P > 5 β 3 <P p- ». 1 O X) LA xp ? P β 1 X 3 p- and O id 1 i — j x: 1 P 1 P rp > 5 OJ 3 1 with 1 β rp rH β β β O ♦ H 3 O O β X> rp 3 β 1 x: P > i • H r-l O <P and q

CA

OX

LA

AND

and x-ip 1 1 P 1 , -. Ρ 1 ο OJ 1 XJ 1 F- <- (· ri β p Ρ 3 O > 5 3 id rP β 1 C 3 >> rp O «Η X 1 • P β ο Ρ * 3 O r; ο 1 Ρ Ρ β lA χ: 3 β ο >> p · AND 1 and

OJ ox

AND

rp Ρ AND 1 OJ Ρ 1 > 1 β β ο 3 Ρ «Η χ: β ο Ο r — l Ρ Ρ «Γ4 Ό χ: β 1 3 Ρ ΙΑ • Ρ Ή - 3 β ρ · 1

- (2-hydroxyethyl) pyrrole-3-carbonitrile p

xo

3id A p Ol Ρ β O t ρ o Φ xj O βΆ P test substance EA HV SE systemic effect · <

w ε

AND

And o

o ε

AND

And o

O

P 3 3 β

ε

AND

And o

O

P ε

AND

And o

o o

P ε

AND

And o

o o

o o

P ε

AND

And o

O

P eI

1 rH 1 P 1 1 β O P β O 3 P 1 Ρ 1 β ο Ρ > 3 P 43 «Μ 1 43 β O O p Ρ Ο Φ β P 1 β ο Ρ 1 AND β P AND P β Ρ Α β > p β '- - ' β β O AND P 1 1 > 3 Ρ 1 P O p C \ l in\ Α Ρ CM <- β β 1 1 -—. β 1 ε Φ p O ε of-. Ρ ο 1 P 43 O P > 3 43 ο AND β β β > 3 43 β β —- 1 CD 43 β Ρ C0 43 1 LÍX id 1 Φ Φ id 1 CM 1 1 ρ- <μ ε 1 • ri ·

phenyl) -5-nitropyrrole

ε cx

I cx φ

co ΡΟ xj ο ΧΡ φ

q

I Φ ε q CX Ρ X <5 CX X W ο ο * >> Ρ I ο ε • Η CX £ 3 ' CX φ Μ ρ ω ο η ο > 3 Ρ η

ε

CX CX Μ Ο ω ο Ρ 1 ε 1 CX σχ CX Ρ OJ ο ο ι ο 1 Ρ

ε χ

cx ε

CX

CX σχ σχ σχ σχ

ΙΓΧ σχ σχ σχ σχ <ί ο

ο ο

Ί “ί ε

cx

CX what σχ σχ σχ σχ σχ σχ σχ

LCX «ο

I

Ρ

X

Ρ

X q

ca>

ο

Ρ η

φ ρ

1 xl- q Ρ q 1 · » q Ρ ο Μ Ρ > 3 q Ρ cx Ρ X OJ Ρ 1 r-x Ρ ο 1 Ρ OJ Ρ q 1 Ρ q 1 > 3 ο CX ο Ρ q q χ q Ρ ο φ q 1 q q Ρ Ρ CC ΙΪΧ > 3 ο χ q I 1 cx χ ο ο Ρ ε q Ρ Ρ X ο Ρ CC X X 1 q > 3 I 1 ο Ρ χ> q Ρ ICX Ρ ι φ X χ Ρ Ρ Ρ 1 -φ AND 1

Ρ 1 P > 3 P X P q Ρ > 3 P φ C p ε 1 Φ q y— * · OJ P O > 3 1 q X X q O q ο O P cc γΗ P X I > 3 X O 1 tSJ O P P q ♦ r-i X 1 φ X 1 P χ 1 •in· O * σχ ·> q - P q 1 Tt - · > 3

CX

X β

x a xd and £ aa and x ω x βο Μ X O 0 xj o £ X X

• M 0 and β and X and XJ <3 X O >> O X Λ4 0 and X and and w and 0 X ω O m O ř >> X n

σχ

CA

CA

CA

I o

-dAJ β

X c ~ a a

and w o ω o x

and a

and o

o o

rH a

and a

o o

X

CA

CA

CA

CA

CA

CA

CA

CA

CA a

and a

o o

O

X a

and a

o o

X

LA O-CO

In f— O

AND

Jd

X

X

X

X β

£>

O

X <n x

X £ AND 1 O £ χ— '» 1 X 1 £ ř * 3 > 3 X O LA £ 1 and X X £ 1 1 > 3 rd £ r—— 1 O 1 £ X AJ £ and • rH O X 1 X β H- > 3 X 1 O of-. £ £ > 3 O 1 Φ ·% and £ £ X X X X β SA £ X) Z — S X O SA > 3 X 4-i 0 £ O £ rH X X 0 β β • rH 4-j £ X O 1 β r— X 0 O £ .—. AA .β X Al β O 0 X 4-i SA X > 3 • rH 0 SA 1 Φ SA • rH 1 £ £ > < X r-H X 0 X £ X x · O £ 1 O 1 • rH X 1 > 3 £ £ 1 - £ Jd and x: • M · ÍM 1 and XJ O Jd LA AJ X 1 1__1 X P LA X X 1 4h m 1 0 AJ • rl 99 . 1 Φ XJ X) 'IN 1 1 1 IA and 1 α 'Φ 1 and 0 l

M β

h and XD P 3Jd P Ό Φ Ρ β O N HO Φ XJ O q-3H

Λί Φ and β Ρ • rH Ρ xj <! W3 W ο ο Το ιΡ ο and • Η Ρ and, Ρ ω W ρ ω ο «Η ο ίο η ιΡ

σχ σχ σχ <3β

Ό ta

1 ιΡ Ρ Ρ «Ο W ο ιΡ and Ρ Ρ ο ο Ρ ο CXI rH

and

P p

o o

rH σχ σχ σχ σχ σχ σχ σχ σχ σχ σχ a

p p

o o

o rP a

P

P o

O

P σχ σχ σχ β

Jd p

XO rp xo β

co>

O

P

Φ

P

σχ AND σχ O 1 ζ — χ 1 γΗ ιΡ χ- ^ řo Ρ (Ρ β q řo • rH Ρ β Ρ Ρ 1 <υ ο β 1 1 1 P »» <Η q ο q O O - ~ x 04 / q Ρ XJ O q x> 1 AND ο ι q fp P q crx q rp 04 / what jZ P what 1 ο Χ3 1 jd O β Λ1 and [Ρ Ο Ό AND • P 1 1 O χ: Ρ Ο ΓΟ Ό P OJ q ο Ό το 1 1 1 1 SW • rl 1 1 (Ρ P x— r-t rH P Ό Ρ η O rp O • H Ό 1 X »/ q m řo q 1 ΙΓΧ ΓΟ 1 q β q P ιΡ řo 1 Φ řo • rH * · Ρ 1 1 P irx <q P £ CJ

-chlorophenyl) pyrrolXO ft 3 M ft X <u χ β o N X O <DKJO ΑΧ X test substance EA HV SE systemic effect tt w

ox ox

B ft

O

O

X ft a

o o

• 3 β

X oa

A ft o

O

X a

and a

o o

O

X a

ft ft o

o x

and a

and o

o o

X a

ft ft o

O

X ox ox ox ox ox

OX

Ox ox ox ox

XO ox ox ox I I 3

A A XI

AND II 1 A ro AND 1 CM X 1 z-s X rH X • rH 1 in-' of-. 1 •AND A ^- X O ♦ rH 1 AND X 1 > 3 X AND z * 3 AND AND 1 z- ^ AND O ft X O AND ro β AND AND ft X AND WHOSE O AND •AND • _ · Φ > 3 • rH - · > 5 1 AND 1 jC AND β 1 AND ft β 1 β I4X > 3 irx AND > 3 O irx AND O O CJ Φ 1 ft l Φ ft 43 l O AND 43 1 AND X of- and and 1-1 AND and X AND AND and AND > 3 X O AND X WHAT O 43 • rH WHAT O O 43 > 3 AND O > 3 AND O β Λ1 AND X AND 43 43 3 β • rH 43 •AND 1 1 43 43 Φ AND 1 X Φ X 1 X AND CM 1 O and Φ ro AND· AND 1 ro 1 1 1 AND 1 1 and

-carbonitrile

Srl fi i-1 and xo a

3> J a <σ φ • fi co N - fi O ω xj O fiX3 rd

JU Φ and C and • fi and XJ fi w O O X >> Λ1 rd CJ and • fi and and and φ « P w O and O > 3 CQ rd

pers

Os

OS i

pers

M ·

OJ

I «3 fi fi t a

and w o ω o rd a

and a

o o

o rd

OS

Os

OS

Os

Os os

OS

OS

OS a

and a

o o

OS

Os

OS a

and a

o o

o rd a

and a

o o

pers

OS

OS

I I I

1 rď O rH fi O 1 rs WHAT zs fi > 3 3 1 Λ1 (fi 1 1 1 fi fi rd rd P - ' x ^ O fi 1 > 3 rd P 9d O xo 1 rd fi O • fi and • fi Φ • W fi rd ďS > 3 fi rd fi OF-*. fi and fi fi 1 C what fi P rH P fi P > 3 fi - Φ Jd CJ > 3 • fi O 1 and fi O <P 1 • fi 1 fi fi 3 and x ~ s CD fi fi OJ fi irs P O rd r * rd > fi O 1 1 1 Φ fi <P and > 3 O • fi r-1 rd rd M- and fi • H rd P fi fi O • fi rd fi what fi and O 03 / 1 O fi fi rS > 3 O P * P ω M • fi fi P '- · fi 3 1 - ' 1 1 P - fi > 3 • fi 1 Φ rd m 1 csj and (fi 1 and fi OJ Ή 1 irs 1 1

-carbonitrile

M a

XD

Jd a Ό Φ and co «a o φ xj o 3X3 and test substance EA HV SE systemic effect <3 w

and a

and o

about what and

and a

o o

and «3> and a

and o

o a

and a

o o

o e

and a

o o

and a

and a

o o

o a

what what what what what what

IOO whats what

O O O 1 and 1 and O O 1 1 3 1 3 • rd and 3 and 3 3 - · > » rd '-of . > 5 and and 1 and • rd t and and -— -in 3 -Φ Z — X 3 1 1 and and 1 and and tco and > » • rd and and 1 O 3 3 O 3 3 and 3 Φ O 3 Φ O >> £ 3 <H £ 3 £ 3 <a £ i 1 — I • rd 3 3 and 3 3 O Ό O and Ό O CD and 1 and Jd 1 and Jd 1 tr \ £ 3 1 ICO £ 3 1 and O and> - CJ CJ 1 CJ 1 1 1 1 CJ

fluoromethyl) pyrrole β

η a χο a 3 λ »a Ό Φ β βθ Ν β Ο Φ X? Χ βΧ3 Η σχ

Λ1 Φ and β and β and kj <X3 M O O β O and β and and and Φ w β w O «0 O >> β n

<3 β

Ό ί—

E

and and 1 w o cn o β and and and irx O O in O CXJ rH

AND

ε a

and ο

ο ο

σχ σχ σχ

XX?

σχ σχ σχ σχ σχ σχ σχ σχ σχ σχ σχ σχ σχ φ

ϋ β

χο

ΧΟ β

φ>

ο β

<π φ

β

I β

1 rH > 5 β β β r · • ιΗ >; β β β Φ ο O and G β β ι O C and 3 ι β 1 OJ and β) AND • H 1 and β β O β ο β -__ β G 1 β 1 ΙΓΧ β 1 and

rH • Η ι 1 β ιχχ Ζ— β 1 β β 1 Ζ— >> β β β £ 3 Ο t > 5 β £ 3 AND of-. G Φ β and β β ε Φ >> φ β 1 β ε ο 1 OJ φ ΐ *. 3 β 1 «Η X β 1 ε β ο <β β O Ο / - · • β ο β β β β β G χ: φ β β 1 υ v — ζ > 1 IN ι 1 1 and

ι β

Ό

AND

β)

AND

CJ

I ε

ο β

£>

AND

N-Chlorophenyl) -5- (trifluoromethyl) pyrrole-3-carbonyl

Ο σχ

ΧΟ Ο. 3 ϋ Ο. Ρ Φ Ρ CO Ν Ρ Ο φ X) Ο β * 3 Ρ

AND

X

CD

Ί

φ and β Ο- • τΗ Ρ- XJ X Μ Ο Χη ο Ρ υ and Ρ ο- and Μ ο. φ Ρ ω ο «0 ο řn Ρ η

• 3 β

X

C— a

οο.

Μ Ο

W Ο

Ρ a

Οοο ο

ο ρ

and οο.

ο ο

σχ σχ σχ σχ σχ σχ σχ σχ σχ a

οο.

ο ο

ο γΗ a

ΟΡΟ ο

Ρ σχ σχ σχ

II II

AND β γΗ • Η 1 and rH O X β O 1 rH C0 ο AND β - řn β 3 and řn 3 Ρ Ρ and P O P P Ρ ο • Η · » O ϋ <P and O Ό β. β β and P P • rl P Ρ β ο - · 1 X β and AND β řn X ι O. 1 P O. \ 0 Ρ ο. β cn 1 • ^ ř - 1 1 C* 1 ® ι β 1 CJ β χ Φ and Ρ _Μ Ρ O CD LA 1 O řn Ρ řn 3 1 1 3 ο α Ρ X X P P P and 1—1 P +3 - ο 1 Ρ O p O řn <H 03 / and Ρ > 4 · φ ♦ ÍH β β β X p Φ - ' 1 and β β P X P β + D ι ο. CD AND P řn p 1 φ P ΙΑ 1 1 Ρ 1 0- β • M · and 1

pyrrole-3-carbonitrile ο

σχ ι

• xf

OJ

AND

XH h and xo and β ϋ and Ό Φ • H CO N -HO Φ XJ O q-β h

φ and β and • Η and XJ * β ο ο rH ο and • Η and and and φ W μ ω ο 05 / ο > 3 Η 05 /

• β β

Ό

Ca 'a

and w o w o rH a

and a

o o

o rH a

o o

rH σχ σχ σχ σχ σχ

ι a

and a

o o

r rH ο- σχ ι <0 ϋ

μ xo

XO β

α>

o μ

η

Φ

-μ a

o o

rH ο σχ ι ι

ι -ν ι

1 rH q O β rH OJ 1 rH 1 q 0 1 1—1 r-f • rH q 1 and χ — X rH > 3 rH > 3 <H O rH 1 β O μ - O χ: • μ q • μ OJ rH q and μ μ q q q 1 q β 1 φ + j > 3 q • r! >> O and and WITH 1 and • μ 0 q and X3 -— 1 ι and r-. - rH μ q 1 q , —T rH O x: 1 rH α LfX O t and r * 3 43 0 and > 3 ϋ 1 β E rH q ♦ f — í rH Ή P3 rH ο and O 03 / I.E and O X) O q μ ϋ 1 »» μ 1 q • μ XJ 1 1 • μ LfX and 1 AFTER X3 q AND LfX and Ό r —- and - 1 -μ AFTER 1 1 1 rj t 1 rH AFTER 1

pyrrole-2,4-dik «arbo-

Claims (25)

A method for controlling insects, nematodes and mites, characterized in that the insects, nematodes and mites, the place where they are propagated, their food or habitat are contacted with an insecticidally, nematocidally or acaricidally effective amount of an arylpyrrole compound of the formula I wherein ( I) represents a hydrogen, fluorine, chlorine, bromine or iodine atom or a trifluoromethyl group; Y is fluorine, chlorine, bromine or iodine, trifluoromethyl or cyano; W is cyano or nitro; A represents a hydrogen atom, a C 1 -C 4 alkyl group optionally substituted by one to three halogen atoms, one hydroxy group, one C 1 -C 4 alkoxy group or one C 1 -C 4 alkylthio group, one phenyl group optionally substituted by an alkyl group 1 to 3 carbon atoms, alkoxy of 1 to 3 carbon atoms or 1 to 3 halogen atoms, further one phenoxy optionally substituted with 1 to 3 halogen atoms or one benzyloxy optionally substituted 249 is a halogen atom, a C1 -C4 alkoxycarbonylmethyl group, a C3 -C4 alkenyl group optionally substituted by 1 to 3 halogen atoms, a cyano group, a C3 -C4 alkynyl group optionally substituted by one halogen atom, a dialkylaminocarbonyl group containing from 1 to 4 carbon atoms in each alkyl moiety or a cycloalkylaminocarbonyl group having 4 to 6 carbon atoms in the cycloalkyl moiety; is hydrogen, fluorine, chlorine or bromine and each independently represents a hydrogen atom, a C1-C3 alkyl group, a C1-C3 alkoxy group, a C1-C3 alkylthio group, a C1-C3 alkylsulfinyl group carbon atoms, C 1 -C 3 alkylsulfonyl, cyano, fluorine, chlorine, bromine or iodine, nitro, trifluoromethyl, the radical of formula R 1 CF ₂ Z, R ₂ CO or NR ₃ R ₄ , or M and R, attached at adjacent positions together with the carbon atoms to which they are attached may form a ring in which MR represents a residue OCH ₂ O-, -OCF ₂ O- or represents a group with (O) _n or oxygen; represents a hydrogen atom, a fluorine atom, a difluoromethyl group, a fluorochloromethyl group or a trifluoromethyl group; 250 R ₂ represents an alkyl group having 1-3 carbon atoms, alkoxy having 1 to 3 carbon atoms or a 'radical NR3R41 R ₃ represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms; R 4 is hydrogen, C 1 -C 3 alkyl or R 8 CO; R ₅ represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms and n is a number of 0, 1 or 2. 2. A process according to claim 1 wherein the arylpyrrole compound is a compound selected from the group consisting of: 4,5-dichloro-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile, 4,5-dichloro-2- (α, α, α-trifluoro-p-tolyl) pyrrole-3-carbonitrile, 2,3-dichloro-4-nitro-5- (α, α, α-trifluoro-p-tolyl) pyrrole, 2,3-dichloro-5- (3,4-dichlorophenyl) -4-nitropyrrole, 4-bromo-2- (p-chlorophenyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile, 3,4-dibromo-5- (3,4-dichlorophenyl) pyrrole-2-carbonitrile, 2,4-dibromo-5- (p-chlorophenyl) pyrrole-3-carbonitrile, 5- (p-chlorophenyl) pyrrole-2,4-dicarbonitrile, 251 3-bromo-5- (3,4-dichlorophenyl) pyrrole-2,4-dicarbonitrile, 4,5-dichloro-1- (ethoxymethyl) -2- (α, α, α-trifluoro-p-tolyl) pyrrole-3-carbonitrile, 4-bromo-2- (p-chlorophenyl) -1- (ethoxymethyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile; and 4-bromo-2- (3,4-dichlorophenyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile. 3. A method for the protection of growing plants from insect, nematode and acarid attack, comprising applying to the leaves of the plants or to the soil or water in which they are growing an insecticidally, nematocidally or acaricidally effective amount of an arylpyrrole compound as defined in of claim 1. 4. A process according to claim 3 wherein the arylpyrrole compound is a compound selected from the group set forth in claim 2. The method of claim 3, wherein the arylpyrrole compound as defined in claim 1 is applied to the plants or to the soil in which the plants grow at a rate of 0.125 to 4.0 kg / ha. 6. A method according to claim 3, wherein the arylpyrrole compound of formula I is applied to the leaves of the plants or to the soil or water in which the plants grow, in the form of a liquid composition containing 10 to 10,000 ppm of the arylpyrrole compound defino. as defined in claim 1. 252 7. An insecticidal, acaricidal and nematicidal composition, characterized in that it contains an arylpyrrole compound as defined in claim 1 as active substance. The insecticidal, acaricidal and nematicidal composition of claim 7, wherein the arylpyrrole compound comprises a compound selected from the group set forth in claim 2. Arylpyrrole compounds of general formula I, wherein the individual symbols are as defined in claim 1, but X is not hydrogen. 10. Arylpyrrole compounds according to claim 9, wherein A is hydrogen or (C1-C4) alkoxymethyl in the alkoxy moiety; W is cyano or nitro; X and Y are each chlorine, trifluoromethyl or bromine; R is fluorine, chlorine or bromine, trifluoromethyl or trifluoromethyloxy; M represents a hydrogen, fluorine, chlorine or bromine atom and L represents a hydrogen or fluorine atom. Arylpyrrole compounds according to claim 9 selected from the group consisting of 4,5-dichloro-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile, 4,5-dichloro-2- (α, α, α-trifluoro-p-tolyl) pyrrole-3-carbonitrile, 2,3-dichloro-4-nitro-5- (α, α, α-trifluoro-p-tolyl) pyrrole, 2,3-dichloro-5- (3,4-dichlorophenyl) -4-nitropyrrole, 253 4-bromo-2- (p-chlorophenyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile, 3,4-dibromo-5- (3,4-dichlorophenyl) pyrrole-2-carbonitrile, 2,4-dibromo-5- (p-chlorophenyl) pyrrole-3-carbonitrile, 5- (p-chlorophenyl) -3- (trifluoromethyl) pyrrole-2,4-dicarbonitrile, 3-bromo-5- (3,4-dichlorophenyl) pyrrole-2,4-dicarbonitrile, 4,5-dichloro-1- (ethoxymethyl) -2- (α, α, α-trifluoro-p-tolyl) pyrrole-3-carbonitrile, 4-bromo-2- (p-chlorophenyl) -1- (ethoxymethyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile; and 4-bromo-2- (3,4-dichlorophenyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile. A process for preparing arylpyrrole compounds of formula Ia wherein M (Ia) represents a hydrogen, chlorine or bromine atom, Y is chlorine or bromine; 254 A is hydrogen; W is cyano or nitro; L represents a hydrogen, fluorine, chlorine or bromine atom; M and R are each independently hydrogen, (C1-C3) -alkyl, (C1-C3) -alkoxy, (C1-C3) -alkylthio, (C1-C3) -alkylsulfinyl, (C1-C3) -alkylsulfonyl; carbon atoms, cyano, fluorine, chlorine, bromine or iodine, nitro, trifluoromethyl, the radical of formula R 1 CF ₂ Z, R ₂ CO or NR ₃ R ₄ , or M and R, attached at adjacent positions together with carbon atoms, to which they are attached may form a ring in which MR represents a residue Z is S (O) _n or oxygen; R 11 represents a hydrogen atom, a fluorine atom, a difluoromethyl group, a fluorochloromethyl group or a trifluoromethyl group; R ₂ represents an alkyl group having 1-3 carbon atoms, alkoxy having 1 to 3 carbon atoms or a radical NR ₃ R _4; R ₃ represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms; 255 R ₄ is hydrogen, C 1 -C 3 alkyl or R ₅ CO; r ₅ is hydrogen or C 1 -C 3 alkyl and n is 0, 1 or 2; characterized in that the benzoylacetonitrile or α-nitroacetophenone corresponding to the general formula tl c-CH ₂ W in which L, M, R and W are as defined above, is reacted at elevated temperature with a dialkoxyethylamine containing 1-4 in each alkoxy moiety carbon atoms, to form α- (2,2-dialkoxyethylamino) -β-cyanstyrene or α (2,2-dialkoxyethylamino) -β-nitrostyrene, each containing from 1 to 4 carbon atoms in each alkoxy moiety and having the general formula in which: Alk is C 1 -C 4 alkyl and L, M, R and W are as defined above 256 and this intermediate is treated with a mineral or organic acid to give the desired arylpyrrole. Process according to claim 12, characterized in that the reaction of 2,2-dialkoxyethylamine having 1 to 4 carbon atoms in each of the alkoxy moieties with benzoylacetonitrile or α-nitroacetophenone is carried out in the absence of a solvent or in the presence of an inert organic solvent. 14. A process according to claim 12, wherein the intermediate a- (2,2-dialkoxyethylamino) -p-cyanstyrene or [alpha] - (2,2-dialkoxyethylamino) β-nitrostyrene containing in each alkoxy moiety C působí působí působí působí působí působí působí působí působí působí působí působí působí působí působí působí působí působí působí působí působí působí působí působí působí působí působí působí působí působí působí působí působí působí působí působí působí působí působí působí působí působí působí působí were each C působí-C uhlíku působí působí, acting with hydrochloric acid, hydrobromic acid, or trifluoroacetic acid. Intermediates for the preparation of arylpyrrole compounds as defined in claim 9, comprising α- (2,2-dialkoxyethylamino) -β-cyanostyrenes and α- (2,2-dialkoxyethylamino) -3-nitrostyrenes of the general formula wherein: Alk is C1-C4alkyl; W is cyano or nitro; L is hydrogen, fluorine, chlorine or bromine; and 257 M and R are each independently hydrogen, (C1-C3) -alkyl, (C1-C3) -alkoxy, (C1-C3) -alkylthio, (C1-C3) -alkylsulfinyl, (C1-C3) -alkylsulfonyl; carbon atoms, cyano, fluorine, chlorine, bromine or iodine, nitro, trifluoromethyl, the radical R ₁ CF ₂ Z, R ₂ CO or NR ₃ R ₄ , or M and R, attached at adjacent positions together with the carbon atoms, to which they are attached may form a ring in which MR represents a residue -OCH ₂ O-, -OCF ₂ O- or Z is S (O) _n or oxygen; R 6 represents a hydrogen atom, a fluorine atom, a difluoromethyl group, a fluorochloromethyl group or a trifluoromethyl group; R ₂ represents an alkyl group having 1-3 carbon atoms, alkoxy sl to 3 carbon atoms or the radical NR ^ R ^; R ₃ represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms; R ₄ is hydrogen, C 1 -C 3 alkyl or R ₅ CO; r ₅ represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms; 258 n is a number of 0, 1, or 2. 16. A process according to claim 1 wherein the arylpyrrole compound of formula I is a compound of formula Ia in which: X is hydrogen, chlorine or bromine; Y represents a chlorine or bromine atom; W is cyano or nitro; A represents a hydrogen atom, a C 1 -C 4 alkyl group optionally substituted with one to three halogen atoms, one C 1 -C 4 alkoxy group or one C 1 -C 4 alkylthio group, one phenyl group optionally substituted with a C 1 -C 3 alkyl group carbon atoms, (C 1 -C 3) alkoxy or (C 1 -C 3) halogen, furthermore represents a C 3 -C 4 alkenyl group optionally substituted by 1 to 3 halogen atoms, or a C 3 -C 4 alkynyl group; L is hydrogen, fluorine, chlorine or bromine; and M and R are each independently hydrogen, C 1 -C 3 alkyl, C 1 -C 3 alkoxy, C 1 -C 3 alkylthio 259 to 3 carbon atoms, C 1 -C 3 alkylsulfinyl, C 1 -C 3 alkylsulfonyl, cyano, fluoro, chloro, bromo or iodo, nitro, trifluoromethyl, the radical of formula R ₂ CF ₂ Z, R ₂ CO or NR ₃ R ₄ , or M and R, attached at adjacent positions together with the carbon atoms to which they are attached, may form a ring in which MR represents a residue -och ₂ o-, -OCF ₂ ° or Z is S (O) _n or oxygen; R 6 represents a hydrogen atom, a fluorine atom, a difluoromethyl group, a fluorochloromethyl group or a trifluoromethyl group; R ₂ represents an alkyl group having 1-3 carbon atoms, alkoxy having 1 to 3 carbon atoms or a radical NR ₃ R _4; r ₃ represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms; R ₄ is hydrogen, C 1 -C 3 alkyl or R 8 CO; R 8 is hydrogen or C 1 -C 3 alkyl and n is 0, 1 or 2. 260 17. The method of claim 16 wherein the arylpyrrole compound is a compound selected from the group consisting of: 4,5-dichloro-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile, 4,5-dichloro-2- (α, α, α-trifluoro-p-tolyl) pyrrole-3-carbonitrile, 2,3-dichloro-4-nitro-5- (α, α, α-trifluoro-p-tolyl) pyrrole α 2,3-dichloro-5- (3,4-dichlorophenyl) -4-nitropyrrole. 18. The process of claim 3 wherein the arylpyrrole compound of formula I is a compound of formula Ia as defined in claim 16. 19. The process of claim 18 wherein the arylpyrrole compound is a compound selected from the group set forth in claim 17. 20. The method of claim 18, wherein the arylpyrrole compound as defined in claim 16 is applied to the plants or soil in which the plants grow at a rate of 0.125-4.0 kg / ha. The method of claim 18, wherein the arylpyrrole compound of formula I is applied to the leaves of the plants or to the soil or water in which the plants grow, in the form of a liquid composition containing 10 to 10,000 ppm of the arylpyrrole compound defined in claim 16. An insecticidal, acaricidal and nematicidal composition, characterized in that it contains an arylpyrrole compound as defined in claim 16 as the active ingredient. 23. The insecticidal, acaricidal and nematicidal composition of claim 22, wherein the arylpyrrole compound comprises a compound selected from the group set forth in claim 17. Arylpyrrole compounds according to claim 9 of the general formula Ia, wherein the individual symbols are as defined in claim 16 but X is not hydrogen and when W is nitro and A is methyl then Y is bromo or M and R are other than methoxy. Arylpyrrole compounds according to claim 24 selected from the group consisting of 4,5-dichloro-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile, 4,5-dichloro-2- (α, α, α-trifluoro-p-tolyl) pyrrole-3-carbonitrile; and 2,3-dichloro-5- (3,4-dichlorophenyl) -4-nitropyrrole.