SK536088A3 - Method for killing insect, nematodes and mites, a method for protecting plants, arylpyrroles and a method and intermediates for produduction thereof - Google Patents

Description

A method of controlling insects, nematodes and mites, a method of protecting plants, a composition, an arylpyrrole and a method and intermediates therefor

Technical field

The invention relates to a method of controlling insects, nematodes and mites and to a method of protecting growing plants from attack by such pests using certain arylpyrrole compounds. Further, the invention relates to an insecticidal, acaricidal and nematicidal composition based on these compounds, novel arylpyrrole compounds per se, and methods and intermediates for the manufacture of 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.

BACKGROUND OF THE INVENTION

While there is extensive literature dealing with various natural and synthetic pyrrols such as antibacterial and fungicidal agents, the arylpyrrols of the present invention differ from the known compounds in their structure and / or insecticidal activity.

Among the known pyrrole compounds, for example, pyrrolnitrin of the formula may be mentioned

1a which has been described in US 3,428,648 and pyrolomycins of the formula

(A) (B)

(C): Q-H (D): Q-Cl

X Y (F) br br 0 * 2 ») and br (P2b) br Cl <P3) Cl and

(US 4,495,358). No insecticidal effect has been reported with these substances.

Also described are 4,5-dihalopyrrol-2-yl-di-trihalomethyl ketones (U.S. Pat. No. 3,963,746). Although a certain acaricidal effect has been declared for these compounds, the comparative experiments described herein have not shown these compounds to be effective insecticides, acaricides and nematicides.

Certain aryl / cyano and aryl / nitropyrrols having a trisubstituted pyrrole functionality are known from Japanese Patent Application J 69001528-B. These compounds are declared as muscle relaxants. The compounds of the invention differ therefrom in that they contain a tetrasubstituted pyrrole functional group and exhibit an insecticidal effect.

Certain pyrroles are also known from US 4,563,472, but neither do they contain a tetrasubstituted pyrrole functional group and have no insecticidal effect.

Also included are the heterocyclic semiconductors disclosed in Japanese Patent Application J 62098562-A include certain pyrroles. Finally, certain pyrroles are also included in EP 206 523. The latter compounds are declared as fungicides. They differ significantly from the compounds of the invention in their structure.

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, a place where they are propagated, their food or habitat with an insecticidally, nematocidally or acaricidally effective amount of an arylpyrrole compound. of formula I

U (I) where

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

Y represents a fluorine, chlorine, bromine or iodine atom, a trifluoromethyl group or a cyano group;

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 my is a carbon or cycloalkylaminocarbonyl group having 4 to 6 carbon atoms in the cycloalkyl moiety;

L is hydrogen, fluorine, chlorine or bromine; and

M and R are each independently hydrogen, (C1-C3) alkyl, (C1-C3) alkoxy, (C1-C3) alkylthio, (C1-C3) alkylsulfinyl, (C1-C3) alkylsulfonyl; up to 3 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 in adjacent positions together with carbon atoms the atoms to which they are attached may form a ring in which MR represents a shock

-OCH ₂ O-, -OCF ₂ O- or

Z is S (O) _n or oxygen;

R ¹ represents a hydrogen atom, a fluorine atom, a difluoromethyl group, a fluorochloromethyl group or a trifluoromethyl group;

R ² is C 1 -C 3 alkyl, C 1 -C 3 alkyl 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 represents a hydrogen atom, a C 1 -C 3 alkyl group or the radical R 4 CO;

R ⁵ represents a hydrogen atom or a C 1 -C 3 alkyl group and n is a number of 0, 1 or 2.

According to a second aspect of the invention there is also provided a method of protecting growing plants from insect, nematode and mite infestation by applying an insecticidally, nematocidally or acaricidally effective amount to the leaves of the plants or to the soil or water in which the plants grow. an arylpyrrole compound as defined above.

The invention also relates to an insecticidal, acaricidal and nematicidal composition which contains 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 symbols are as defined above, but X is not a hydrogen atom.

C 4 -C 6 Cycloalkylaminocarbonyl means a C 4 -C 6 cycloalkylamino group bonded directly to the carbonyl group via a nitrogen atom.

A preferred class of novel arylpyrroles of the invention are those compounds of formula (II) wherein:

A, L, M, of the invention

(II)

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) in which

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

Another group of preferred arylpyrroles of the invention are compounds of formula IV

(IV) in which

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

Yet another group of preferred arylpyrroles according to the invention are compounds of formula V

(V) in which

A, L, M, R, W, X and Y have the meanings given above and of formulas VI and VII

(VI)

In which

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

Preferred arylpyrrols of the formula I according to the invention are those in which A represents a hydrogen atom or a (C 1 -C 4) alkoxymethyl group, W represents a cyano or nitro group, L represents a hydrogen or fluorine atom, X and Y are independently of one another in each case a chlorine atom, a bromine atom or a trifluoromethyl group, M represents a hydrogen, fluorine, chlorine or bromine atom and R represents a fluorine, chlorine or bromine atom, a trifluoromethyl group or a trifluoromethoxy group.

Preferred compounds of formula (II) which are particularly effective as insecticidal, acaricidal and / or nematicidal agents are those in which A represents a hydrogen atom or a (C1-C4) alkoxymethyl group, L represents a hydrogen atom, M represents hydrogen, fluorine, chlorine or bromine, R is fluorine, chlorine or bromine, trifluoromethyl or trifluoromethoxy, W is cyano, and X and Y are each independently chlorine, bromine or trifluoromethyl.

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 Br,

R represents a fluorine, chlorine or bromine atom, a trifluoromethyl group or a trifluoromethoxy group, W represents a nitro group and X and Y each independently represent a chlorine atom, a bromine atom or a trifluoromethyl group.

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-carbonitrile,

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-nitro-pyrrol,

2,3-dichloro-4-nitro-5- (α, α, a-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-nitro-pyrrol,

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

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

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,

5-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-bis- (trifluoromethyl) pyrrole,

5- [p- (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-dicarbonyl nitrile, 1-allyl-4-nitro-5- (α, α, α-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-l- (p-chlorophenoxy) methyl-5- (p-chlorophenyl) -3-nitro-pyrrol,

2,4-dibromo-5-phenyl-pyrrol-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,

- [m- (difluoromethoxy) phenyl] -2- (trifluoromethyl) pyrrole-3-carbonitrile,

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

4-chloro-5- (β-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 - [(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 - [(1-methoxy) ethyl] -5- (p-chlorophenyl) -4- (trifluoromethyl) pyrol2,3-dicarbonitrile,

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

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

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

1 - [(3,4-dichloro-benzyloxy) 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) -l-methyl-4-nitro-pyrrol-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) pyro1-2-karbonitri1,

3-bromo-5- (m-bromophenyl) -2-nitro-pyrrol,

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

2- (p-iodophenyl) -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-bis- (trifluoromethyl) pyrrole,

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

5- (3-bromo-4-cyanophenyl) -2-nitropyrrole-3T-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 - [(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,

- (3-bromo-4-ipropoxy) -5-nitro-3- (trifluoromethyl) pyrrole,

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

2- (3,4-dichlorophenyl) -5-nitro-pyrrol-3-carbonitrile,

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

4-bromo-2- (3,4-dichlorophenyl) -5-nitro-pyrrol-3-carbonitrile,

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

2- (m-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-nitro-pyrrol,

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

2,3-dichloro-4- (3,5-difluorophenyl) -5-nitro-pyrrol,

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,

- (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-methyl-phenyl) -5-nitro-pyrrol-2-carbonitrile,

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

4- (m-bromophenyl) -3-chloro-5-nitro-pyrrol-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-nitro-pyrrol,

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-nitro-pyrrol,

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

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

5-bromo-4- [p- (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- (trifluoromethyl) pyrrole .

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-isopropyloxy (carbonylmethyl) -5-nitropyrrole-2-carbonitrile,

3- (o-bromophenyl) -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- [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,

5-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-H-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-nitroPyrol),

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- (p-bromophenyl) -1 - [(2-methoxy) ethyl] pyrrole-2,3-dicarbonitrile,

- (m-1-propionaminidophenyl) -3-nitroprole-2-carbonitrile,

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

5-chloro-4- (p-chlorophenyl) -l-hydroxyethyl-3-nitro-pyrrol-2-carbonitrile,

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

4- (4-chloro-2-methyl-phenyl) -l-isopropylthiomethyl-3-nitro-5- (trifluoromethyl) pyrrole-2-carbonitrile,

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

2-chloro-3- (m-difluoromethoxy-phenyl) -4-nitro-pyrrol,

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-nitro-pyrrol-2-carbonitrile,

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

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

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

3- (3-cyano-4-methyl-phenyl) -l-methyl-4-nitro-5- (trifluoromethyl) pyrrole-2-carbonitrile,

2,3-dichloro-5- (3,4-dichlorophenyl) -4-nitro-pyrrol,

2- (3,5-dibromo-4-methoxyphenyl) -4,5-dichloropyridine-3-carbonitrile,

2,3-dichloro-4-nitro-5- (2,4,6-trifluorophenyl) -4-nitro-pyrrol,

4,5-dibromo-2- (2,3,6-trifluorophenyl) -3-carbonitrile,

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

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

4,5-dichloro-2- (3,4-dichlorophenyl) -l-ethyl pyrrole-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-cyanostyrene and α- (2,2-dialkoxyethylamino) -β-nitrostyrene compounds in which each alkoxy moiety each contain from 1 to 4 carbon atoms correspond to the following general formula

C * = CHW

I

NH - CH ₂ CH (OAlk) ₂ wherein

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 are each independently hydrogen, (C1-C3) -alkyl, (C1-C3) -alkoxy, (C1-C3) -alkylthio, (C1-C3) -alkylsulfinyl, (C1-C3) -alkylsulfonyl; up to 3 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 in adjacent positions together with carbon atoms the atoms to which they are attached may form a ring in which MR represents a residue

-CH ₂ O-, -OCF ₂ O- or

Z is S (O) _n or oxygen;

R ¹ represents a hydrogen atom, a fluorine atom, a difluoromethyl group, a fluorochloromethyl group or a trifluoromethyl group;

R ² is C 1 -C 3 alkyl, C 1 -C 3 alkyl or a radical NR ³ R ^4;

ABOUT ,

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

R ⁴ represents a hydrogen atom, an alkyl group having 1 to 3 carbon atoms or the radical R ⁵ CO;

R ⁵ represents a hydrogen atom or a C 1 -C 3 alkyl group and n is a number of 0, 1 or 2.

A preferred group of β-substyrstyrene compounds of the invention are those 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 bonded in adjacent positions together with the carbon atoms to which they are attached may form a ring in which MR is the radical of the formula

Another preferred group of β-substyrstyrene 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 bonded in adjacent positions together with the carbon atoms to which they are attached may form a ring in which MR is the radical of the formula

Although these compounds of the invention are referred to above as β-cyanostyrenes and β-nitrostyrenes, they may also be referred to as dialkyl acetals.

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

1) p-chloro-β-E (formylmethyl) amino] cinamonitrile 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) -β - [(formylmethyl) amino] -1-naphthalenacrylonitrile diethyl acetal,

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

6) N- (formylmethyl) -. Beta.-methyl-.alpha .- (nitromethylene) benzylamine diethyl acetal;

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

8) N- (formylmethyl) -α- (nitromethylene) -2-naphthalenemethylamine 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-p - [(formylmethyl) amino] cinamonitrile dimethylacetal,

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

13) 3,4-dichloro-p - [(formylmethyl) amino] cinamonitrile diethyl acetal a

14) p-Trifluoromethyl-β-E (formylmethyl) amino] cinamonitrile diethyl acetal.

β-Cyanostyrenes, also referred to as cinamonitrildialkylacetals, may be prepared by reacting substituted or unsubstituted benzoylacetonitrile with 2,2-dialkoxyethylamine of 1 to 4 carbon atoms in each alkoxy moiety in the presence of an aromatic solvent to give α (2,2-dialkoxyethylamino) - β-cyano-substyrene having 1 to 4 carbon atoms in each alkoxy moiety, which can be carried out by reaction with trifluoroacetic acid to give 2-substituted phenylpyrrole-3-carbonitrile. Chlorination of the resulting cyanophenylpyrrole with sodium hypochlorite or sulfuryl chloride in an inert solvent affords insecticidal, acaricidal and nematicidal 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 ° C and 40 ° C. The reactions can be described by the following reaction scheme.

aromatic solvent

cf ₃ co ₂ h or γ HCl

R

NaOCl or with ₂ or ₂ or ₂

KOC _{(CH3) 3}

A-I

A

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, (C 1 -C 4) alkoxy or halo, (C 3 -C 4) alkenyl optionally substituted by (C 1 -C 3), or (C 3 -C 4) alkynyl, X represents chloro or bromo, R ⁶ is C 1 -C 4 alkyl and L, R and M are as described 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 of N-formyl-DL-phenylglycine or substituted H-formylphenylglycine of general formula of formula

VIII

(VIII) in which:

L is hydrogen, fluorine, chlorine or bromine; and

M and R are each independently hydrogen, (C1-C3) alkyl, (C1-C3) alkoxy, (C1-C3) alkylthio, (C1-C3) alkylsulfinyl, (C1-C3) alkylsulfonyl; up to 3 carbon atoms, cyano, fluorine, chlorine, bromine or iodine, nitro, trifluoromethyl, R ¹ CF ₂ Z, R ² CO or NR ² R 4, or M and R, attached to adjacent positions together with 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 ¹ represents a hydrogen atom, a fluorine atom, a difluoromethyl group, a fluorochloromethyl group or a trifluoromethyl group;

R ² is C 1 -C 3 alkyl, C 1 -C 3 alkyl 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 represents a hydrogen atom, an alkyl group having 1 to 3 carbon atoms or the radical R ⁵ CO;

R ⁵ represents a hydrogen atom or a C 1 -C 3 alkyl group and n is a number of 0, 1 or 2.

with at least an equivalent amount of 2-chloroacrylonitrile and 2-3 equivalents of acetic anhydride. The reaction is carried out at elevated temperature, preferably at about 70 to 100 ° C.

By the above reaction scheme:

the reaction can be described as follows

The 2-phenylpyrrole-3-carbonitrile thus prepared or

The 2-substituted-phenylpyrrole-3-carbonitrile is readily converted to the corresponding 4-halo-, 5-halo- 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 hydrogen solvent.

The preparation of monohalogenated pyrrole-3-carbonitrile requires the use of about one equivalent of the halogenating agent, whereas two to three equivalents of the 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 ° C and 30 ° C, and the elemental bromine is usually operated at about 30-40 ° C. C. Other halogenating agents that can be used for this reaction include sodium hypochlorite, tert-butyl hypochloride, N-bromosuccinimide, N-iodosuccinimide, and the like. The reaction can be described by the following reaction scheme.

The carbonitriles of formula II according to the invention can also be prepared by reacting substituted or unsubstituted benzoylacetonitrile with 2,2-dialkoxyethylamine of up to 4 carbon atoms in each alkoxy group, in the presence of an aromatic solvent, resulting in α- (2,2-dialkoxyethylamino) -p C 1 -C 4 -cyanine-substyrene in each alkoxy group, which is then converted to 2-substituted-phenylpyrrole-3-carbonitrile by reaction 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 ⁶ is C 1 -C 4 alkyl and L, R and M are as defined above.

h ₂ nch ₂ ch (oc ₂ h ₅ ) ₂

aromatic solvent

or

In accordance with the invention, the 3-nitro-2-phenylpyrrole and 3-nitro-2-substituted-phenylpyrrole compounds of formula II may also be prepared by reacting α-nitroacetophenone or substituted α-nitroacetophenone with 2,2-dialkoxyethylamine containing 1 in each alkoxy moiety up to 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) -β-nitrostyrene or substituted α- (2,2-dialkoxyethylamino) -β-nitrostyrene, wherein each alkoxy moiety contains from 1 to 4 carbon atoms, which is then converted to a carbon atom

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 reactions can be described by the following reaction scheme.

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 form tert. butyl (benzoyl or subst. benzoyl) cyanoacetate. This reaction may be described by the following reaction scheme.

L

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 benzoyl nitriles are shown in the following tables

- 49 Tert-Butyl (benzoyl and Sub-benzoyl) cyanoacetates

L M R temperature mp H 3-C1 4-C1 91 - 94 H H 4-OCF ₃ 81 - 84 H H 4-Br 113 - 115 H H 4-CP 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 - 119,5 H H 4-CHF ₂ CF ₂ O 92 - 94 3-C1 5-C1 4-CH ₃ O -

- 50 Benzoylacetonitrile

L M R melting point to H H 4-C1 128.5 to 129.5 H 3-C1 4-C1 105-107 H H 2-C 153-155 H H 4-OCF ₃ 79-81 H H 4-CF ₃ 44 - 45 H 2-C1 4-C1 66 - 67 H H 3-C1 80-83 H H 4-CN 126-128 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 4-0¾ 103.5 to 106 H H 4-NO ₂ 119-124 3-C1 5-C1 4-OCH 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, e.g. alkanol having 1 to 4 carbon atoms and potassium tert-butoxide. This reaction yields an arylpyrrole having the same substituents as the starting material but, in addition to them, a C 1 -C 4 hydroxyalkyl group on nitrogen. Instead of bromoalkanol having 1 to 4 carbon atoms, cyanogen bromide can be used in this reaction to give the corresponding arylpyrrole of formula I substituted on the nitrogen with cyano. These reactions can be described by the following reaction scheme, in which BrAlkOH is C1 -C4 bromoalkanol, K ⁺ Ot-Bu is potassium tert-butoxide, L, M, R, W, X and Y are as in formula I and A is 1) a hydroxyalkyl radical having 1 to 4 carbon atoms or 2) a 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 reaction of the resulting bromofumaronitrile nitrile with N- (trimethylsilyl) 53 methyl-5-methylbenzenethioimidate 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 the appropriately substituted H (trimethylsilyl) methyl-5-methylbenzenethioimidate is used in the previous reaction. The procedure described above can be described by the following reaction scheme.

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

Br ₂ / CHCl ₃ / _A

CN (-HBr)

br

..-.-. 2 ..- · ’- - · -. ··· -’...........-. / ?.

HMPA / 3 eq. HgO (-TMS, -HBr, -CH-JSH)

N

H

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

The arylpyrrols of the invention effectively kill insects, mites and nematodes. Accordingly, the compounds can be used to protect growing or harvested crop plants from attack by the aforementioned pests.

In order to ensure effective protection of the aforementioned crops from insect, mite and / or nematode infestation, in practice about 10 to about 10,000 ppm, preferably from about 10 to about 10,000 ppm, are applied to plants, harvested crops or land on which they are grown. 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. The compounds of the invention can also be used to protect lawns on sports grounds and racecourses from attack by various pests such as caterpillars and others, for example Blissus leucopterus.

Arylpyrols of the formula I according to the invention are also effective in killing insects, nematodes and mites when applied to the leaves of plants and / or to the soil or water where the plants are growing, at a dose ranging from about 0.125 kg of active ingredient per hectare to 4.0 kg of active ingredient. substances per hectare. Of course, higher application rates of arylpyrroles of formula I may be used to protect crops from insect, nematode and mite infestation, but these higher rates are generally unnecessary and harmful to the environment.

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

The 2-aryl-3-cyano-4,5-dihalopyrrols prepared from the β-cyanostyrene compounds of the invention are effective in killing 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 from about 100 ppm, are generally applied to plants, harvested crops or soil on which they are grown to effectively protect said useful crops from insect, mite and / or nematode attack. up to 5,000 ppm of halogenated arylpyrrole dispersed in water or other cheap liquid carrier.

The aforementioned halogenated arylpyrrols are also effective in killing insects, nematodes and mites when applied to plant leaves and / or to the soil or water where the plants are growing, at a dose ranging from about 0.125 kg active ingredient per hectare to 4.0 kg of active substance per hectare. Obviously, higher application rates of halogenated arylpyrroles may also be used to protect crops from insect, nematode and mite infestations, but such higher doses are generally unnecessary and harmful to the environment.

The aforementioned arylpyrrols may advantageously be formulated into dry compact granules, suspension concentrates, granular preparations, wettable powders, emulsifiable concentrates, powders, powder concentrates, microemulsions, etc., all of which can be used to protect plants by application to soil, water and / or 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 invention can be prepared by co-grinding about 3 to 20% by weight of an arylpyrrole of formula I with about 3 and 20% by weight of an anionic surfactant. One suitable anionic surfactant is sodium sulfosuccinic acid dialkyl ester, in particular an 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 prepared by grinding about equal parts, usually about 3 to 20 parts, of arylpyrrole and a solid surfactant with about 60 to 94 parts of gypsum. The mixture 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 marketed by BASF Wyandotte Corporation under the designation Pluronic 10R8, 17R8, 25R8, F38, F68, F77 or F87. These copolymers are particularly suitable for the preparation of compressed granules.

In addition to powders and the aforementioned concentrated formulations, 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 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 preparations may be applied sequentially or a formulation comprising a mixture of the two components may be applied.

Likewise, 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 preparations according to the invention should contain from 0.001 to 0.1% by weight of active arylpyrrole according to the invention.

The invention is illustrated by the following examples, which are not intended to limit the scope of the invention in any way.

Signal intensities in IR spectra are indicated by the following symbols:

w weak m medium with strong w wide belt

Signal shapes in NMR spectra are indicated by conventional abbreviations.

Example 1

2-phenyl-pyrrol-3-carbonitrile

The following procedure is analogous to the method described in J. Org. Chem., 43, 4273-4276 (1978). 30.00 g of PI-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 give 42.5 g of a brownish orange semi-solid. The product is partially purified by silica gel chromatography. According to the proton NMR spectrum, this was a mixture of 73% 2-phenylpyrrole-3-carbonitrile and 27% 2-phenyl-3-cyano-5-methylpyrrole. Recrystallization from chloroform once and recrystallization from 1,2-di62 chloroethane twice gave 1.69 g of off-white solid, which was 96% by 2-phenylpyrrole 3-carbonitrile according to the proton NMR spectrum. Mp 148-152 ° C;

Microanalysis (MW 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

To a solution of 2.00 g (11.9 mmol) of 2-phenyl-3-cyanopyrrole in 80 mL of methylene chloride, 1.90 mL (3.19 g; 23 ml) was added dropwise over 5 minutes while cooling with water and stirring with a magnetic stirrer. 6 mmol) of sulfuryl chloride. The temperature of the mixture was maintained between 5 and 10 ° C during the addition. Stirring is continued at 5-10 ° C for a further 90 minutes, then the reaction mixture is vacuum filtered to isolate 1.28 g of a solid material having a temperature of 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, concentrated in vacuo and the residue triturated with hexane. 0.60 g (21.3% yield) 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-dichloro-2-phenylpyrrole-3-carbonitrile in orange-brown solid, m.p. 254-255 ° C.

IR (nujole suspension) V _max ^: 3165 (bs), 3120 (s), 2245 (s), 1570 (m), 1513 (m), 1440 (s), 1252 (m), 1069 (m), 996 (m), 920 (m), 768 (s), 698 (s),

665 (s) cm ^'1.

1 H-NMR (dimethylsulfoxide, δ values): 7.73 (d, J = 6.6 Hz, 1.97H, 2 phenyl protons on C ₂ and C _g ), 7.52 (t, J = 7.3 Hz) 2.04 H, two phenyl protons on C ₃ and C ₅ ), 7.44 (t, J = 7.3 Hz, 1.0 H, one phenyl proton on C ₄ ).

C-NMR (dimethylsulfoxide, δ values): 137.51 (C ₂ carbon pyrrole), 129.25 (C ₄ phenyl carbon), 129.04 (C ₃ and C ₅ phenyl carbons), 128.37 (C 1 phenyl carbon) ), 125.88 (C ₂ and C _{g of} phenyl carbons), 114.32 (either C _g pyrrole carbon or carbon-nitrile), 114.14 (either C ₅ carbon pyrrole or the nitrile carbon group), 110.72 (C ₄ carbon pyrrole), 89,78 (C ₃ carbon pyrrole)

Microanalysis (molecular weight 237.09):

calculated: 55.72% C, 2.55% H, 11.82% N, 29.91% Cl; Found: C 55.78, H 2.59, N 11.12, Cl 29.74.

Example 3 p-Chloro-β - [(formylmethyl) amino] cinamonitrile diethyl acetal

A solution of 250.00 g (1.39 mol) of p-chlorobenzoylacetonitrile and 203 ml (185.95 g; 1.39 mol) of 2,2-diethoxyethylamine in 1300 ml of dry toluene was refluxed for 20 hours with Dean- Stark pen in which 23.8 ml (95.2% of theory) of water was collected. The hot, turbid dark brown solution containing a large amount of undissolved solids was filtered through a pad of diatomaceous earth and after dilution with 200 ml of ethyl acetate was 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 solidified slowly. After recrystallization from hot cyclohexane, the solid material yielded 324.26% (79.1% yield) of an orange waxy solid. The NMR spectrum indicated that this product consisted of the 78% (Z) -isomer and the 23% (E) -isomer of the p-chloro-β - [(formylmethyl) amino] cinamonitrile diethyl acetal. The product melts at 60 to 72'C. The following analytical data applies to another sample prepared in an analogous manner.

IR (mull in nujol) V _ma ^x: 3327 (s), 3065 (m), 2197 (s), 1600 (s), 1530 (s), 1314 (m), 1265 (m), 1173 (m), 1154 (m), 1128 (s), 1100 (s), 1060 (s), 1022 (s), 939 (m), 895 (m), 844 (s), 768 (m), 730 (m) cm “ ¹ .

1 H-NMR (chloroform, δ 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 (E) (t, J = 5.1 Hz, 1.05H, one methine proton and acetal carbon), 4.07 (E) and 4.05 (Z) (s, 0.83H, β-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)

- 67 (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, 4.90H, six methyl protons of one of the two ethoxy groups).

C-NMR (chloroform, S-values): 161.21 (α-enamine carbon), 136.29 (Z) and 134.60 (E) (either the C 1 or C ₄ phenyl ring carbon), 134.08 (Z) and 132.30 (e) (BUCF or _C4 atoms of the phenyl ring), 129.34 (Z), and 129.89 (e) (either a C ₂ and C _g and C ₃ and C ₅ of the phenyl ring), 128.94 (Z), and 128.63 (e) (either a C ₂ and C _g and C ₃ and C ₅ of the phenyl ring), 121.19 (Z) and 119.50 (E) of the nitrile carbon), 99.43 (Z ) and 100.63 (E) (β-enamine carbon), 61.88 (Z) and 63.25 (E) (methane of the acetal residue), 62.64 (z) and 63.03 (E) (methylene) ethoxy carbons), 46.32 (Z) and 47.33 (E) (ethylene ethylene carbon), 15.26 (ethoxy methyl carbons).

Microanalysis (MW 294.78):

calculated C 61.11, H 6.50, N 9.51, Cl 12.03, found C 61.25, H 6.25, N 9.34, Cl 12.35,

Example 4

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

CN /

+ CF ₃ CO ₂ H (molecular weight 114.02)

Cl (MW 202.64)

To 108 ml of trifluoroacetic acid was added 5.00 g (0.183 mol) of solid ρ-σ1ι1όΓ-β - [(formylmethyl) amino] cinamonitrile diethyl acetal over 5 minutes with stirring at 23 ° C. This addition causes 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 a further 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 then 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) V _max ^: 3275 (bs), 2225 (s), 1502 (s), 1410 (m), 1275 (m), 1200 (m), 1108 (s), 1023 (m), 999 is (m), 908 (m), 843 (s), 752 (s), 695 (s), 620 (s) cm ^-1 .

1 H-NMR (acetone, δ values): 11.22 (very broad s, 0.99H, one proton in the NH group of the pyrrole residue), 7.82 (d, J = 8.9 Hz, 2.46H, two aromatic) phenyl protons), 7.51 (d, J = 8.9 Hz, 2.46H, two aromatic phenyl protons), 7.02 (t, J =

2.6 Ηζ, Ι, ΟΙΗ, one pyrrole proton per C ₅ ),

6.58 t, J = 2.6 Hz, 0.77H, one pyrrole proton at C _4).

C NMR (acetone, δ values): 13.73 ₍₂ C pyrrole carbon), 134.42 (C ₄ carbon p-chlorophenyl), 129.93 (methine carbons at positions 3 and 5 of the phenyl ring), 128.07 (meth carbons at positions 2 and 6 of the phenyl ring), 121.21 (C ₅ carbon pyrrole), 117.93 (nitrile carbon), 113.78 (C ₄ carbon pyrrole), 90.86 (C ₃ carbon 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 above procedure or using concentrated hydrochloric acid instead of trifluoroacetic acid, the following compounds are obtained:

M and / or R melting point (• c) the acid used 4-C1 165-166 horses. HCl, CF ₃ COOH 3,4-Cl 216-221 cf ₃ cooh 2-C1 156-157 cf ₃ cooh 4-OCF ₃ 143-145 cf ₃ cooh 4-0F ₃ 179-180 cf ₃ cooh 2,4-di-Cl 197-199 CF ₃ C00H 3-C1 150 -.156 cf ₃ cooh 4-CN 210-212 cf ₃ cooh 4-F 167-170 horses. HC1 4-SO ₂ CH ₃ 221-221.5 cf ₃ cooh 3,4-F 173 - 175.5 cf ₃ cooh 3-CF ₃ 166-168 cf ₃ cooh 4-COOCHj 155.5 - 158 cf ₃ cooh _4-CH3 117-137 cf ₃ cooh 4-N0G 174-177 cf ₃ cooh

Example 5

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

Sat ₂ or ₂

Cl

To a mechanically stirred solution of 2- (p-chlorophenyl) pyrrole-3-carbonitrile (16.83 g, 83.1 mmol) in glacial acetic acid (450 mL) was added dropwise 14.7 mL (24.70 g; 183.0 mmol) of sulfuryl chloride. The addition induces a slight exothermic reaction associated with the rise of the te73 fence to 39'C. After a further 16 minutes, the reaction mixture is filtered; the collected 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 (mull in nujol) \) ^_max: 3170 (br), 3100 (m), 2225 (s), 1508 (m), 1097 (m), 825 (p), 717 (a), 660 (m) cm “ ¹ .

1 H-NMR (dimethylsulfoxide, S 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 (DMSO, δ values): 136.01 ₍₂ C pyrrole carbon), 133.92 (C ₄ carbon p-chlorophenyl),

129.09 (C ₃ and C ₅ carbons of p-chlorophenyl), 127.41 (C ₄ carbon of p-chlorophenyl), 127.11 (C 3 carbon of chlorophenyl), 114.49 (carbon of nitrile group), 114.10 (C ₅ carbon pyrrole), 110.92 (C ₄ carbon pyrrole), 90.09 (C ₃ carbon pyrrole).

Microanalysis (MW 271.54):

calculated: C 48.65, H 1.86, N 10.32, Cl 39.17, found C 49.22, H 2.12, N 9.85, Cl 39.03.

Example 6

4,5-dibromo-2- (a, a, 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 mixture was stirred overnight to give a white solid which was filtered off. Thin layer chromatography (ethyl acetate-hexane 1: 1) is a single component product. The above-prepared substance melts above 230 ° C.

Analysis calculated for: ^C 12 ^H 5 ^Br 2 ^F 3 ^N 2 calculated C, 36.55; H, 1.27; N, 7.11; Br, 40.61; Found: C, 36.40, H, 1.08, N, 6.99, Br.

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

·· -. i ·.> ·. · - · - •. · ·. » : ...... 'ϊ ;;' ΐ / · ΦίΛ · .... ..., · ..: ..; ...... • «· - 76 - x CN . \ L / FROM \\ _U A Y H - / ^ p L U R X Y temperature melting (° c) H H 4-NOG 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 H 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-OCE ₃ Cl Cl 222-225 H H 4-OCF ₃ br br 231-232 H H 4-OCF ₃ Cl H

y * ** *. • 'IF **! · · *'. *. . ·. * ** · / *> {'' * ** ‘· *» \ * ·. »» *. <> ** - ·. ’· - 1 ·. ' . «.. ** · · V V V V V V. «· ·. ·· '**' * '%. . . . ·

L U R X Y temperature melting ( H H 4-CN · ' br br > 230 H H, 4-CN Cl Cl > 240 H H 4 -SO ₂ CH ₃ br br > 230 H H 4 -NOg Cl Cl 246-249 U 3-Cl 4-Cl br br > 260 H H 3 -CF ₃ Cl Cl > 230 H H 4 -COCH-j Cl Cl 251-254 H 2,3-CH = CH Cl Cl 244-247 H H 4 -CH ₃ Cl Cl 215-217 H 2-C1 4-C1 br br > 230 The H 3 -Cl Cl Cl > 230 H 2-C1 4-C1 Cl Cl > 230 H H 4 -C 1 br br 273-274 H H 2 -C 1 br br > 230 H H 4 -CF ₃ Cl Cl > 230 H H 4-Br Cl Cl y 235 H H 2 -C 1 Cl Cl > 230

 .in.'.·'. • »· *. - 78 - R • k · »<“ »» ·. ....... r melting point ( ^e c; X Y L U H 3-C1 4-C1; Cl Cl > 235 H H H Cl Cl 254-255 H H 4-C1 Cl Cl 255-257 H H 4-CF ₃ br br > 230 H H 4-C1 Cl br 262-263 (Decomposition) H H 4-C1 br Cl 250-258 (Decomposition) H 3-C1 5-Cl Cl Cl > 230 H 3-C1 4-C1 Cl br > 230 2-C1 4-C1 5-F Cl Cl 207-210

Example 7

3-nitro-2-phenylpyrrole

5.7 g (0.0345 mol) of α-nitroacetophenone are dissolved in 100 ml of toluene, and 4.6 g (0.0345 mol) of diethyl acetal and acetonitrile are added. The reactants were introduced into a quarter-liter round bottom flask equipped with a DeanStark collar. The box is filled with molecular sieves (4 x 10 &lt; ^{10 &gt;} m) and the mixture is heated under reflux for 18 hours. Evaporation of the toluene in vacuo gave 8.36 g of brown oily α- (2,2-diethoxyethylamino) -p-nitrostyrene.

To this oily material was added 50 ml of concentrated hydrochloric acid and the flask was circulated to turn the oily material into 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 DEG-192 DEG.

ID: 1485 cm ^-1 (NO ₂ )

H-NMR (CDCl3 / d6): 6.73 (m, 2H), 7.46 (m, 5H).

Example 8

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

N

H + NbOCl

To a mixture of 1.56 g (0.0083 mol) of 3-nitro-2-phenylpyrrole in 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 5 minutes then acidified with concentrated hydrochloric acid. 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 with ethyl acetate / hexane mixtures containing an increasing portion of ethyl acetate. Evaporation of the appropriate fractions gave 0/77 g (36%) of a yellow solid, m.p. 190-190.5 ° C.

For ^C 10 ^H 6 ^N 2 ° 2 ^Cl 2 calculated C, 46.72; H, 2.35; N, 10.90.

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

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

• »-T ·· ·« · «and ^« ·· »<rt« • í ^ SŽiM'rt ·· »^ * · '* λ <# 3Ϊ3 $ Ϊ *. ·:

'β · rt> rt

L U R X Ϊ melting point ( ^e C) H H H Cl Cl 190 to 190.5 H 4-C1 H Cl Cl 214-215 H 4-C1 H br br 203-204 (dec H H H br br 148.5 to 149 3-Cl 4-C1 C Cl Cl 219-220 (dec H 4-Br H Cl Cl 222-223 (dec H H 4-CF ₃ Cl Cl 166-168

Example 9

4,5-dichloro-2- (3,4-dichlorophenyl) -l-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 a clear brown solution to which was added 1 equivalent of tert. of potassium butoxide. After a few minutes, the mixture turns into a clear 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 next 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, substituting 4,5-dichloro-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile with appropriately substituted phenylpyrrole-3-carbonitriles or 3-nitro-2-subst. the following compounds are obtained by phenylpyrrole.

A L M R X Ϊ temperature CC) mp 0¾ H H 4-C1 Cl Cl 152 - 153 C ₂ H ₅ OCH ₂ H 3-C1 4-C1 Cl Cl 128 - 130 ° 2 ^H 6 H 3-C1 4-C1 Cl Cl 137 - 138 ch ₃ H 3-C1 4-C1 Cl Cl 154 - 156 ch ₃ U H 4-CF ₃ br br 145 - 146 c ₆ h ₅ -ch ₂ H H 4-CF ₃ br br 145 - 147 c ^ -eHg H 3-C1 4-C1 Cl Cl 95 - 96 Chg-Chg = CH H 3-C1 4-C1 Cl Cl 69 - 70 CH ₉ '= C-CH ₀ C Cl H 3-C1 4-C1 OR Cl CH 2 = C-CH ₂ H 3-C1 4-C1 Cl Cl 147 - 148 ch ₃ sch ₂ H 3-C1 4-C1 Cl Cl

A L U R X Ϊ melting point CC) C _{(CH3) 3} H H 4-0F ₃ Cl Cl ch ₃ H U 4-CF ₃ Cl Cl 99-100 C ^ SCgHj H 3-Cl 4-C1 Cl Cl 74-75 0 N Q ₂ K 2 -QQ-C ₂ 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 CgHjOCHg H H 4-OCF ₃ Cl Cl 46 - 47 CH ₃ H H 4-OOF ₃ Cl Cl 72-73 C ₆ ^h 5 ^-CH 2 H H 4-OCF ₃ Cl Cl oil C ^ OCH H H 4-C1 Cl Cl - boy ₂ ch ₂ H 3-Cl 4-C1 Cl Cl 143-145 KC H 3-Cl 4-C1 Cl Cl 251-252 CgHjCHjOCHg H 3-Cl 4-C1 Cl Cl 88-89 Cl o-ch ₂ The 3-Cl 4-C1 Cl Cl 118-120 ic «c-ch ₂ H 3-Cl 4-C1 Cl Cl 115-116 ch ₃ H H 4-C1 br CF ₃ 126-139

A L U R X Ϊ melting point (CC) C ₂ H ₅ OCH ₂ H H 4-C1 br cf ₃ 91-92 Cghj-OCH H 3-C1 4-C1 Cl Cl 118-120 c ₂ h ₅ -och ₂ H H 4-C1 br br 104-105 C ₆ H ₅ C 2 ^h H H 4-C1 br br 81-82 ch ₃ H H 4-C1 br br 197 - 201 CN H H 4-CF ₃ Cl Cl 138-139 CGH ^ -OCHg H H 4-CF3 br CF ₃ 104-105 C-VOCÍL, H H 4-CF ₃ H CF ₃ 76 - 77 -C ^ OCH H 3-C1 4-C1 br cf ₃ 80 - 81 At EXAMPLE 10

l-benzyl-4,5-dibromo-2- (a, a, a-trifluoro-p-tolyl) pyrrole-3-carbonitrile

In a 100 ml flask, mix 1.5 g of 4,5-dibromo-2-α, α, α-trifluoro-p-tolyl) pyrrole-3-carbonitrile and 50 ml of dry tetrahydrofuran and mix the resulting clear dark solution with stirring add 1 equivalent of potassium tert-butoxide. After a few minutes, the resulting solution became clear, 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). as follows.

Water (50 ml) was added and the resulting mixture was extracted with chloroform (4 x 50 ml). The organic phases are combined, washed four times with 50 ml of a 10% aqueous sodium hydroxide solution each time, the organic layer is dried over magnesium sulphate 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

CH ₂ OC ₂ H ₅

Dissolve 1.0 g (0.003 mol) of 4,5-dichloro-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile in 10 ml of dry tetrahydrofuran and add 0.37 g (0.0033 mol) first. 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. The white solid was collected and dried to give 1.0 g (91%) of the title compound, mp 128-130 ° C.

Example 12

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

f Vcx + 2 NaOCl dioxane

To a solution of 17.87 g (88.2 mmol; 1.00 equivalents)

2- (p-chlorophenyl) -3-cyanopyrrole in 800 ml dioxane was added dropwise with stirring at 20 ° C over a period of 30 minutes with 250.15 g (5.25% by weight) of sodium hypochlorite (13.13 g; 176). , 4 mmol; 2.00 equivalents). The reaction mixture was stirred at room temperature for 30 minutes, then poured into 2200 ml of water, the resulting mixture was freed from a small amount of solid black by vacuum filtration and the filtrate acidified to pH 2 with concentrated hydrochloric acid. Wash with water to give 22.1 g of a brown solid which is treated with 100 mL of 5% aqueous sodium hydroxide, dissolving most of the material and leaving only a small amount of black solids undissolved. This black material was dissolved in 100 mL of ethyl acetate, and the solution was washed with 75 mL each

5% aqueous sodium hydroxide solution, water and saturated aqueous sodium chloride solution, the ethyl acetate layer is dried over magnesium sulfate, clarified with charcoal and, after filtration, rotovapped in vacuo. 1.10 g (5.3% yield) of a slightly orange brown solid are obtained, which, after recrystallization from ethyl acetate / chloroform, yields 0.51 g (2.4% yield) of an 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

Cl

2.0 g (0.008 mol) of 2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile by heating to 40 to 50 ^and C in 100 ml of dioxane, the solution is cooled to 30 ° C and to it was added 1, 3 g (0.008 mol) of bromine. After stirring at room temperature for 1 h, 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.

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

Example 14

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

0.158 8 (0.005 mol) of 5-bromo-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile is dissolved in 5 ml of tetrahydrofuran, an equivalent amount of tert-butyl hypochlorite is added and the solution is stirred overnight.

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

Analogously, 2-bromo-3-chloro-5- (3,4-dichlorophenyl) -4-nitropyrole can be prepared using 2-bromo-5- (3,4-dichlorophenyl) -4-nitropyrrole as starting material.

Example 15

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

To a solution of 0.17 g (0.67 mmol; 1.00 equivalents)

Of 4-chloro-2- (p-chlorophenyl) pyrrole-3-carbonitrile in 100 ml of chloroform was added dropwise a solution of 0.20 ml (0.62 g; 3.88 mmol) at 22 ° C under magnetic stirring over 30 minutes. 5.79 equivalents of bromine in 5 mL of chloroform. 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, when mixed with a mixture of hexane and methylene chloride and subsequent vacuum filtration, yields 0.23 g of off-white, feather-white solid, melting with decomposition at 262-263 ° C.

Example 16

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

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 at 45 ° C with magnetic stirring was added dropwise 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. 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 stirred at room temperature for 19.5 hours and then evaporated in vacuo to give 1.49 g of a slightly orange white solid which was stirred with a mixture of hexane and methylene chloride. After vacuum filtration, 1.33 g (100% yield) of a white fluffy white solid melting at 250-258 ° C is obtained.

Example 17

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

HOAc

To a solution of 2.40 g (11.8 mmol, 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 over 5 minutes using a syringe, 0.75 ml (1.26 g; 9.34) over 5 minutes. mmol (0.79 equivalents) of sulfuryl chloride. About 5 minutes after the addition is complete

100 solids precipitated from the reaction solution. 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 the product with a purity of 97% by weight and a melting point of 258 5 to 261 * c.

Example 18

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

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 1 equivalent of methyl iodide by pipette while the solution was lightly lit. 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 in the flask. After addition of 50 ml of water, a clear solution is formed first, from which a solid precipitate is formed.

This solid material was filtered off and compared to the starting material 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 bottom flask, 0.5 g of 2- (3,4-dichlorophenyl) -1-methylpyrrole-3-carbonitrile is mixed with 35 ml of glacial acetic acid. The mixture is gently heated with an immersion cooker to dissolve all the pyrrole.

103

To the resulting clear solution, 2 equivalents of sulfuryl chloride was added by pipette, 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 thin layer chromatography (25% ethyl acetate in hexane) and IR spectroscopy identical to that of Example 9. 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 tert. of potassium butoxide in 50 ml of dioxane was added with stirring and refluxing 0.98 g (7.8 mmol) of bromoethanol. The reaction mixture was stirred at reflux for 12 hours, then cooled, diluted with 50 ml of water and extracted with chloroform several times. The combined chloroform extracts were dried (MgSO 4) and concentrated in vacuo. The solid residue was dissolved in ethyl acetate with heating, then the solution was cooled, leaving a predominantly starting pyrrole. The mother liquor was concentrated and the residue was recrystallized from 20% ethyl acetate in hexane. 0.31 g of white solid is obtained, m.p. 143-145 ° C.

105

Analysis for: ^C 16 ^H 23 ^NO 4 Calculated C 44.57%, H 2.29%, N 8.00%, Cl 40.57%; Found: C, 44.77; H, 2.29; N, 8.06; Cl, 40.14.

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-butoxide106. After 30 minutes, a solution of 583 mg (5.5 mmol) of cyanogen bromide in 1 mL of tetrahydrofuran was added and the reaction 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. 1.0 g of white crystalline product is obtained, m.p. 250.5-252.0.

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

¹³ C-NMR (perdeuterodimethylsulfoxide, S-values):

102.7 (N-CN), 113.7 (3-CN).

Mass spectrum: 331.9 (M + 1).

For ^C 12 ^H 3 ^cp 4 ^N 3 (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

NaOH

CH1

108

To a mixture of 1.91 g (5.5 mmol) of 4,5-dichloro-2- (3,4-dichlorophenyl) -1- (2-propynyl) pyrrole-3-carbonitrile and 500 ml of methanol is added first with stirring. ml of 10% aqueous sodium hydroxide and then 0.70 g (2.7 mmol) of iodine. The reaction mixture is stirred for 12 hours, then acidified and diluted with 200 ml of water. The precipitated solid material 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-alkylarylpyrroles of formula III, IV, V, VI or VII of the invention to the corresponding N-substituted-3-iodo-2-propylarylpyrrole of the invention.

Example 23

Preparation of 2- (3,4-dichlorophenyl) -4,5-diodopyrrole-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-iodosuccinimide. The reaction mixture was stirred at 25 ° C for several hours until a thin layer (silica gel; ether-petroleum ether-acetic acid 100: 100: 1) sample showed 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 400 ml of water five times to remove the succinimide. The ether phase was dried over sodium sulfate and evaporated in vacuo. 2.0 g (32.3%) of a gray-brown solid are obtained, which releases red vapors on heating and has a melting point above 230'C.

Example 24

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

A solution of 0.65 ml (0.01 mol) acrylonitrile and 2.4 g (0.01 mol) N- (trimethylsilyl) methyl-S-methylbenzenethioimidate in 100 ml tetrahydrofuran was cooled to -5 ° C in an ice / acetone cooling bath. 1.0 N solution was added dropwise over 30 minutes in a nitrogen atmosphere

111

IN tetrahydrofuran solution of tetrabutylammonium fluoride in 20 ml tetrahydrofuran. The resulting solution was stirred for 30 minutes at -5 ° C, then allowed to cool slowly 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, giving 1.2 g (70% of theory) of an off-white solid having the same spectral data as described by Tsuge [J. Org. Chem. 52, 2523 (1987)].

Analysis for:

C, 77.65; H, 5.88; N, 16.47. Found: C, 77.55; H, 5.83; H, 16.39.

The product has a melting point of 95 to 97'C.

112

Example 25

Preparation of 2-phenylpyrrole-4-carbonitrile

DDQ / DME / pyridine h / room temperature

NC

In nitrogen atmosphere, 0.23 g (0.001 mol) of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone and 0.1 g (0.001 mol) of 2-phenyl-1 are dissolved in 13 ml of 1,2-dimethoxyethane. -pyroline-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.

113

The resulting suspension 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 semisolid residue is obtained which, after recrystallization from ethylene dichloride with decolourisation of 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- (trimethylsilyl) methylS-methylbenzenethioimidate using tetrabutylammonium fluoride as a catalyst (a procedure analogous to that described above for the preparation of 2-phenyl-1-pyroline-4-carbonitrile).

For ^C 11 ^H 8 ^N 2 calculated C 78.57, H 4.76%, N 16.67%. Found: C, 78.65; H, 4.70; N, 16.43.

The product has a melting point of 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. After recrystallization from dichloroethane (charcoal purification), the solid residue yielded 0.6 g of the desired final product melting at 239-242 ° C.

115

Analysis calculated for: ^C 11 ^H 6 ^Br 2 ^N 2 calculated

40.49% C, 39.88% C,

H 1.84%, H 1.87%,

49.08% Br, 48.81% Br,

N, 8.59. 8.48% N.

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

Example 27

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

THF room temperature

116

To a vigorously stirred mixture of magnesium shavings (0.64 g, 26 mmol) and tetrahydrofuran (10 mL) in a 100 mL three-necked round bottom flask equipped with a thermometer, a 60 mL dropping funnel and a nitrogen inlet was added at 25 ° C. 4.7 g (26 mmol) of 2- (2-bromomethyl) -1,3-dioxolane in 40 ml of tetrahydrofuran was added dropwise. The rate of addition is 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 suspension of potassium-3,4- with rapid stirring. dichlorobenzoate. The mixture is stirred at 25 ° C for 24 hours, then 50 ml of diethyl ether and 15 ml of 3N hydrochloric acid are added and the layers are 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. A beige-colored semi-solid residue is obtained which, after chromatography on silica gel, eluting with hexane / ethyl acetate (3: 1) as eluent, gives 4.3 g (60%) of the desired ketoacetal as a white solid, m.p. C.

Example 28

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

CHO

To 30 ml of a 0.2 M solution of oxalic acid 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-dioxolane). 2-yl) propiophenone. The reaction mixture was heated at reflux for 1 hour, then allowed to cool, most of the ethanol was evaporated on a rotary evaporator and 100 ml of diethyl ether was added to the residue along with 20 ml.

118 saturated aqueous sodium bicarbonate solution. The layers are separated, the organic phase is dried over magnesium sulphate and evaporated on a rotary evaporator. Chromatography on silica gel using hexane / ethyl acetate (3: 1) as eluent gave 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 heated to reflux for 20 minutes, allowed to cool, most of the ethanol evaporated on a rotary evaporator, and 200 ml of a mixture of equal portions of dichloromethane and diethyl ether together with 50 ml of water were added. The layers were separated, the organic phase was dried over sodium sulfate and evaporated on a rotary evaporator. Chromatography on silica gel using hexane / ethyl acetate (3: 1) as eluent gave 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

1) DMF / POCl ₃

Cl

2) NaOAc

120

0.6 ml (6.5 mmol) of phosphorus oxychloride was added dropwise to the 10 ml dimethylformamide presented in a 50 ml round bottom flask with stirring under nitrogen. The reaction solution spontaneously warms up and slightly yellows. After stirring for twenty 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, 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 acid. The reaction mixture was heated at 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 5- (3,4-dichlorophenyl) pyrrole-2-carbonitrile (0.5 g, 2.1 mmol) in tetrahydrofuran (20 mL) was added N-bromosuccinimide (0.8 g, 4.2 mmol) portionwise under nitrogen. 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 using hexane / ethyl acetate (3: 1) as the title compound

123 eluent. 0.5 g (60%) of the desired dibromopyrrole is obtained in the form of a brown solid which melts above 250 ° C.

Example 33

Preparation of 4-phenylpyrrole-3-carbonitrile

To a mixture of cinnamonitrile (5.0 g, 39 mmol) and (p-tolylsulfonyl) methyl isocyanide (7.6 g, 39 mmol) in dimethylsulfoxide (35 mL) and ether (65 mL) 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 left under nitrogen for 1 h

The reaction mixture is diluted with ether and water. The ether layer was separated, dried (MgSO4) and concentrated in vacuo. The oily residue is chromatographed on silica gel, eluting with a mixture of equal parts of chloroform and ethyl acetate, to give 2.5 g of a cream-colored solid, which is recrystallized from ether / hexane to give 1.15 g of the desired compound, m.p. ° C

References: Tetrahedron Letters 5337 (1972); mp 128-129 ° C.

Example 34

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

125

To a stirred mixture of 4-phenylpyrrole-3-carbonitrile (0.66 g, 3.9 mmol) and dry tetrahydrofuran (20 mL) was added 0.66 mL (1.11 g) via syringe over 4 minutes with cooling in water at 6 ° C. 8.2 mol) of sulfuryl chloride. Cool the mixture to 5-10 ° C for 45 minutes, then cool! 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 0.95 g of a dark colored solid which, after recrystallization from chloroform, gave 0.42 g of off-white crystals melting at 195-196 ° C with decomposition.

For ^C 11 ^H 6 ^Cl 2 ^N 2 calculated C 55.72, H 2.55, N 11.82, Cl 29.91; 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. For the synthesis of 2,6-dibromo-4- (p-chlorophenyl) pyrrole-3-carbonitrile, bromine in dioxane was used in the procedure of Example 33 instead of sulfurochloride and tetrahydrofuran.

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

To a mixture of 5.63 g of a 60% suspension of sodium hydride in oil and 200 ml of dry ether under nitrogen was added a solution of a mixture of 23.5 g (122 mmol) of ethyl p-chlorocinamate and 19.4 g (122 mmol) of (p-tolylsulfonyl). of methyl isocyanide in 180 ml of ether and 80 ml of dimethylsulfoxide. The addition takes about 20 minutes and the mixture spontaneously gently

128 boils 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. s

Analysis for: ^C 13 ^H 12 ^C1NO 2 calculated 62.53% C, 4.81% H, 5.61% N, 14.23% C? 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 previous example) and the recrystallized product from the previous example is stirred under reflux with 150 ml of 10% aqueous hydroxide for 2.5 hours. solution. 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 was 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. The chloroform solution is dried (MgSO4) and treated with charcoal and concentrated in vacuo to give 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

To 0.86 g (12 mmol) of dimethylformamide in 10 ml of ethylene dichloride was added, under cooling in ice, 1.49 g (12 mmol) of oxalyl chloride in 10 ml of ethylene dichloride over 25 minutes. 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 reaction mixture was poured into 50 ml of ice-water and 6 ml of 50% sodium hydroxide solution, extracted with ether and chloroform, the combined organic phases were dried over magnesium sulphate and concentrated in vacuo. Silica gel eluting with ethyl acetate / hexane gave 0.63 g of off-white solid which was used directly to convert to 3- (p-chlorophenyl) pyrrole-2-carbonitrile.

132

Example 38

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

To 0.63 g (3.1 mmol) of 3- (p-chlorophenyl) pyrrole-2-carb aldehyde in 10 ml of water was added 0.52 g (4.6 mmol) of hydroxylamine-O with little stirring and ice-cooling. of 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. The precipitated solid product is a mixture of the above product and the starting aldehyde according to the NMR spectra of 133. 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, then cooled, the precipitated solid was collected and purified by silica gel chromatography eluting with ethyl acetate / hexane. 0.40 g of a pink colored solid is obtained, m.p. 114-115 ° C.

Example 39

preparation

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 with a melting point above 250'C are obtained.

Analysis for ^{: c} ll ^H 5 ^Br 2 TIN calculated 36.63% C, 1.39 % H, 44.38% Br, 9.85% Cl, 7.77 % N; found 36.92% C, 1.32 % H, 44.62% Br, 9.88% Cl, 7.50 % N. At to 1 < ad 40

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

135

Ethyl 4- (p-chlorophenyl) pyrrole-3-carboxylate (1.6 g, 0.0064 mmol) was dissolved in tetrahydrofuran (40 mL) and 1.14 g (0.0064 mmol) was added in small portions at 25-28 ° C. mmol) of H-bromosuccinimide. After the addition was complete, 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 was purified by slurrying in hexane / ethyl acetate (80:20) to isolate the insoluble solid to give 1.3 g (90%). 62%) of a solid, m.p. 161-164 ° C.

Analysis for: C ^ Hj ₃ BrClN ₂ Calculated 47.50 24.33 47.39 Found 24.29% C, 3.34% H, 4.26% N,% Br 10.80% C;

% C, 3.38% H, 4.12% N,% Br, 10.77% Cl.

136

Example 41

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

+ 10% NaOH -—

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 all solids have dissolved, the reaction mixture is refluxed for a further 40 minutes, then refluxed

137 was cooled, filtered and the filtrate acidified. The precipitated white precipitate was collected and dried. 8.0 g (58%) of a solid with a melting point above 205'C are obtained, the NMR spectrum of which (perdeuterodimethylsulfoxide) contains a signal for a pyrrole proton at δ = 7.52. The mass spectrum also corresponds to the monobrominated product.

Example 42

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

N

H

138

8.0 g (0.026 mol) was added to 24 ml of aminoethanol.

5-bromo-4- (p-chlorophenyl) pyrrole-3-carboxylic acid, the resulting suspension is slowly warmed to 110-120 ° C and held at this temperature 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 a slower progressing minor 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 of 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 a further 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.

Analysis for CnH ₆ BrClN ₂ calculated 46.90 % C, 2.13 % H, 9.95 % N, 12.61 % Cl, 28, 39 % Br; found 47.20 % C, 2.09 % H, 9.80 % N, 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 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 of this

141 g of 1.6 g of material were purified by flash chromatography using hexane / ethyl acetate (75:25) as eluent. 0.8 g of a gray-colored solid is obtained, m.p. 191-194 ° C

Analysis calculated for: C ₁₁ H ₅ Br ₂ ClN ₂ calculated

C 36.61, C 9.84, C 37.46, 9.53%,

H, 1.38; N, 7.76; Br, 44.3;

H, 1.25; N, 7.41; Br, 42.99.

Example 45

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

S0 ₉ NC + NaH

142

Cl

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) of 3,4-dichloro-p-nitrostyrene and 10.8 g (5.5 mmol) of (p-tolylsulfonyl) methylisocyanide in 50 ml of dimethyl sulfoxide is added to the suspension over 15 minutes. 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, is purified by chromatography on silica gel, eluting with chloroform / ethyl acetate (4: 1). 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 DEG-188 DEG C. with decomposition.

143

For ^C 10 ^H 6 ^Cl 2 ⁿ 2 ° 2 calculated C, 46.72; H, 2.35; N, 10.90.

Found: C, 46.96; H, 2.60; N, 9.77.

Example 46

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

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) of sulfuryl chloride over 1 minute.

144

After an additional hour, the reaction mixture was diluted with 100 mL of saturated sodium bicarbonate solution and 300 mL of ether, the organic layer was separated, dried over magnesium sulfate and concentrated in vacuo. The brown solid is chromatographed on silica gel using chloroform / ethyl acetate (4: 1) as eluent. The orange-colored 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-phenylpyrene melting at 193-194 ° C with decomposition was also prepared as described in Examples 45 and 46 above.

Example 47

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

(CH gNCHO

DMF

145

3.0 g (0.015 mol) of 2- (p-chlorophenyl) -3-cyanopyrrole, prepared as described in Example 4, were 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 is added, the solution is stirred for 4 hours, then poured into water to precipitate 3.4 g (100%) of a white solid. A sample of this material, weighing 1.0 g, is 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, mp 235-240 ° C.

The following analogues were prepared according to the procedure of Example 47.

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-bromo-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. The solid has a melting point above 225 C ^e and mass spectrum consistent with the assigned structure.

The following additional compounds were prepared as described in Example 48 above.

148

R L melting point ("C) 3-C1 4-C1 > 250 H 4-OCF 218-223 H 4-CF ₃ 239-241 Example 49

Preparation of bromofumaronitrile

149

Fumaronitrile (15.6 g, 0.2 mol) in chloroform (150 ml) was heated to reflux under nitrogen to give a clear solution, to which a solution of bromine (5.3 ml, 0.2 mol) was added dropwise over 30 minutes. 25 ml of chloroform. This addition causes slow decoloration 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 to leave an amber oil whose mass was roughly the same as calculated for bromofumaronitrile. The oily material is distilled in a ball distillation apparatus at a pressure of 27 Pa while maintaining the temperature below 120 ° C (rapid decomposition of the material occurs above this temperature). A semi-solid residue is obtained which slowly migrates to a waxy amber-colored substance with a melting point of 43-47 ° C.

Analysis for: C ₄ HBrN calculated 30.57% C, 0.64% H, 17.83% N;

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 hexamethylphosphoramide under a single atmosphere of stirring at room temperature under nitrogen at room temperature. 1.6 ml (0.09 mol) of water is added, which is washed with 10 ml of hexamethylphosphoramide. An exothermic reaction begins almost immediately in the solution, causing the temperature to quickly rise to 100'C and then drop. The resulting dark red solution was 20 hours

151 was stirred at room temperature and then poured into ice water. A resin material precipitated which slowly turned to a beige-colored solid, which was filtered off and washed on the filters with cold water and dried. After further drying in a vacuum oven at 60 ° C, the product is recrystallized twice from ethylene dichloride with activated charcoal to give a white powdery solid, m.p. 197-200 ° C.

Analysis for: ^C 12 ^H 7 ^N 3 calculated 74.61% C, 3.63% H, 21.76% N;

Found: C, 74.45; H, 3.84; N, 21.61.

Example 51

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

152

1.4 g (0.0075 mol) of 2-phenylpyrrole-3,4-dicarbonitrile are introduced into 35 ml of chloroform under nitrogen, most of the solid material being dissolved. A solution of 0.4 ml (0.008 mol) of bromine in 5 ml of chloroform was added over 20 minutes. Initially the color of the mixture disappears rapidly, but as soon as it begins to precipitate: the resinous product, the coloring persists. The reaction mixture was stirred at room temperature for 30 minutes and then refluxed as the resinous material turned to a solid product. The reaction mixture was heated to reflux for 90 minutes, then cooled, and its sample was 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 is added in a single portion and refluxing is continued for a further 45 minutes. After this time, the mixture contains 10% of starting material. An additional 0.2 ml (0.004 mol) of fresh bromine (bromine was added) was added

153 was added to the refluxing slurry) and refluxing was 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 material 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 product is filtered off.

Analysis Found: Cl 2 ^H 6 ^BrN 3 calculated 52.94% C, 2.21% H, 15.44% N, 29.41% Br; found C 51.64, H 2.35, N 14.91, Br 28.69.

Melting point 225-258 ° C.

154

Example 52

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

CN

Cl + HNO ₃ + Ac ₂ O

Cl

To a mixture of 50 ml of acetic anhydride with 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 is slowly warmed to 30C and maintained at a temperature of 30-33 ° C until all solids

155 the material goes 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 chromatography on silica gel, eluting with hexane / ethyl acetate (75:25). 0.7 g of a yellow solid is obtained, m.p. 228-231 ° C.

Analysis calculated for: ^C 11 ^H 5 ^Cl 2 ^N 3 ^O 2 requires 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 manner 2- (p-chlorophenyl) -5-nitropyrrole-3-carbonitrile, m.p. 201 DEG-206 DEG C., is obtained using 2- (p-chlorophenyl) pyrrole-3-carbonitrile as starting material. Similarly, 2- (p-trifluoromethylphenyl) pyrrole-3-carbonitrile yielded 2 (p-trifluoromethylphenyl) -5-nitropyrrole-3-carbonitrile, m.p. 164-165.5 ° C.

156

Example 53

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

dioxane

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

157

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 red-brown solid, mp 195-200. C.

Analysis for C- ^H ^BrCl ^N -ClC

calcd. 36.57 % C, % Br, 1.10% H, 11.63 % N, 22.13 19.67 % Cl; found 36.46 % c. 1,29% H, 11.50 % N, 21.63 % br. 19.28 % Cl.

Following the procedure of Example 53, 2- (p-chlorophenyl) -5-nitropyrrole-3-carbonitrile gave 4-bromo-2- (p-chlorophenyl) -5-nitropyrrole-3-carbonitrile, m.p. 180-185 ° C.

158

Example 54

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

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) of 90. % nitric acid. As a result of the ongoing exothermic reaction, the temperature rises to 45 ° C and the mixture turns to a green-colored solution. The reaction mixture was stirred for 2 hours then poured into 50 mL

The mixture was stirred vigorously for 5 minutes. The precipitated beige-colored 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, m.p.> 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 25C under nitrogen is added dropwise a solution of 0.3 g (2.1 mmol). of bromine in 5 ml of dioxane. The reaction mixture is stirred overnight, then 50 ml of water are added, 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 brominated pyrrole is obtained as a yellowish solid with a melting point 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 a single portion 1.7 ml (0.012 mol) of trifluoroacetic anhydride, resulting in an immediate temperature rise to about 40 ° C and formation of a yellow color on the surface of the solid material. As the mixture slowly warms to 70 ° C, some of the solid material dissolves into orange amber oil. All solid material dissolves in about 2 hours and heating is continued for 1 hour.

161

The solvent was evaporated under reduced pressure on a rotary evaporator, toluene was added twice to the residue, which was always evaporated under reduced pressure. Trifluoroacetic acid, however, can still be sensed from the final residue. The yellow semi-solid product, obtained in theoretical yield, has a purity of more than 90% by HPLC. 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 ml) is added in one portion. (10 mol) of 2-chloroacrylonitrile. The reaction solution was stirred and refluxed under nitrogen for 18 hours, and the resulting reddish brown solution was cooled to -5 ° C in an ice / acetone mixture, precipitating a precipitate which was filtered off and washed with a small amount of cold nitromethane. resultant

After recrystallization from hot ethylene dichloride, 162 g of red-brown solid gave 1.8 g (56% of theory) of the desired product as white crystals melting at 238 DEG-241 DEG 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-CH3 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 heated to reflux 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 was cooled and the solvent was evaporated 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 acid

164 acetic. The material was dissolved in 75 ml of hot toluene to a cloudy solution, which was clarified with charcoal and filtered. A white solid precipitated from the reddish 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 filters and then in a vacuum oven at 45 ° C. 1.2 g (ca. 60% of theory) of the product melting at 247-250 ° C decomposes.

For ^C 12 ^H 5 ^BrClF 3 ^N 2 calculated 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%.

Bromination of the respective 2-aryl-5- (trifluoromethyl) pyrrole-3-carbonitrile, prepared as described in Example 57, by the above procedure, gave the following farther compounds.

165

H H 235 - 238 H _4-CH3 244 - 245 3-Cl 4-C1 218 - 223 H 4-CF ₃ 225 - 226

Example 59

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

166

To 2.0 g (0.011 mol) of (4-chlorophenyl) glycine was added in a single portion 3.1 ml (0.022 mol) of trifluoroacetic anhydride, giving an immediate yellow coloration and, to some extent, refluxing. heat to reflux, whereby

167, all solid material was 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. To give a very thick oil _(as 1800 cm ^"1). 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 its color turned dark red. The solvent was evaporated under reduced pressure and the dark colored residue was dissolved in dichloromethane. A small amount of insoluble matter was removed by filtration. The material was fractionated by dry silica gel column chromatography using 3% 2-propanol in dichloromethane as eluent. The eluate is collected in suitable fractions. Evaporation of one fraction yielded the desired product as a yellow solid which, after recrystallization from acetonitrile with decolourising charcoal, gave 0.2 g of a pale yellow solid melting under partial decomposition at 238-241 ° C.

168

H ₂ NCH ₂ CH (OEt) ₂

A solution of p-chlorobenzoylacetonitrile (1.39 mol, 250.0 g), 2,2-diethoxyethylamine (203 ml, 185.9 g; 1.39 mol) and dry toluene (1300 ml) was heated under reflux with a magnetic stirrer for 20 hours. condenser, the resulting water being trapped in a Dean-Stark pen (23.8 mL; 95.2% of theory). The hot turbid 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 was recrystallized from hot cyclohexane to give 324.2 g (79.1% yield).

169 orange colored waxy fabric. According to NMR spectroscopy, this product is a mixture of 78% (Z) - and 23% (E) -isomers of p-chloro-p - [(formylmethyl) amino] cinnamonitrile diethyl acetal, m.p. 60-72 ° C. The following analytical data are available for another similarly prepared sample.

IR (nujol suspension) V _max ^: 3325 (s), 3065 (m), 2197 (s),

1600 (sec), 1530 (sec), 1314 (sec), 1265 (sec),

1173 (m), 1154 (m), 1128 (m), 1100 (s),

1060 (s), 1022 (s), 939 (m), 894 (m),

844 (s), 768 (m), 730 (m) cm ^-1 .

1 H-NMR (chloroform, δ values): 7.47 (d, J = 8.6 Hz, 2.12H, two aromatic protons), 7.37 (d, J = 8 Hz, 2.12H, two aromatic protons ), 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) , 1.05H, one methine proton on acetal carbon), 4.07 (E) and 4.05 (Z) (s, 0.83H, proton in β-position of enamine), 3.71 (E) and 3, 68 (Z) (q, J = 7.1 Hz, 2.22H, two methylene protons of one of the two ethoxy groups),

170

3.56 (Z) and 3.53 (E) (q, J = T, 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, 4.90H, six methyl protons of two ethoxy groups).

C-NMR (chloroform, S values): 161.21 (α-enamine carbon), 136.29 (Z) and 134.60 (E) (either or C ₄ phenyl ring), 134.08 (Z) and 132 , 30 (E) (either C 1 or C ₄ phenyl ring) 129.34 (Z) and 129.89 (R) (Either C ₂ or C _{3 5} phenyl ring), 128.94 (Z) and 128.63 (E) (either C _{2 6} or (C ₃ , ₅ phenyl ring)), 121.19 (Z) and 119.50 (E) (nitrile carbon), 99.43 (Z) and 100.63 (E) (β-enamine carbon), 61.88 (Z) and 63.25 (E) (methine carbon of the acetal group), 62.64 (Z) and 63.03 (E) (methylene carbons of ethoxy groups), 46.32 ( Z) and 47.33 (E) (methylene carbon of the ethylamino group), 15.26 (methyl carbons of the ethoxy groups).

Microanalysis (Molecular Weight):

calculated: 61.11% C, 6.50% H, 9.51% N, 12.03% Cl; Found: C, 61.25; H, 6.25; N, 9.34; Cl, 12.35.

171

The procedure described above is replaced by p-chlorobenzoyl acetonitrile in each case with the corresponding benzoylacetonitrile and / or

The 2,2-diethoxyamine in each case with an appropriate 2,2-dialkoxyethylamine containing from 1 to 4 carbon atoms in each alkyl moiety gives the following compounds.

Alk = alkyl of 1 to 4 carbon atoms

ϊ.

- 172 L Μ R (OAllcJg melting point (· C)

HH p-CH ₃ OCO

H p-CH ₃ H

p-Cl H H

H p-CH ₃ H

H m-Cl p-Cl

HH p-OCF ₃

HH p-CF ₃

(oc ₂ h ₅ ) ₂ > 68-73 (O ₂ h ₅ ) ₂ 59 - 69 (oc ₂ h ₅ ) ₂ červenooranžov semisolid product (oc ₂ h ₅ > ₂ 62-70 (OCH ₃ ) ₂ - (OOH ₃ ) ₂ - (oc ₂ h ₅ ) ₂ - (OC ₂ h ₅ ) ₂ - (00 ₂ h ₅ ) ₂ · <«Β

173

Example 61

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

+ CF 3 CO ₂ H

To 108 ml of trifluoroacetic acid was added 54.00 g (0.183 mol) of solid p-chloro-p - [(formylmethyl) amino] cinamonitrile diethyl acetal with stirring at 23 ° C over 45 minutes. During the addition, an exothermic reaction occurs, with the temperature rising to 38 ° C and a solid precipitate begins to precipitate 32 minutes after the addition begins. Reaction mixture

174 was stirred at room temperature for 30 minutes and then vacuum filtered. The solid material is 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 analogue sample.

IR ( _nujole suspension) - 3275 (bs), 2225 (s), 1507 (s), 1410 (m), 1275 (m), 1200 (m), 1108 (s), 1032 (m), 999 (m), 908 (m), 843 (s), 752 (s), 722 (s), 695 (s), 620 (s) cm ^-1 .

H-HMR (acetone, δ values): 11.22 (very broad singlet;

0.99 H, one proton of the N-H 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 on the C ₅ pyrrole), 6.58 (t, J = 2.6 Hz, 0.77H, one proton on C ₄ pyrrole).

C-NMR (acetone, δ values): 137.73 (C ₂ pyrrole), 134.42 (chlorophenyl at C ₄ ), 129.93 (meth carbons at positions 3 and 5 of the phenyl ring), 121.21 (C ₅₎ pyrrole), 117.93 (nitrile carbon), 113.78 (C ₄ pyrrole), 90.86 (c ₃ pyrrole).

175

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. 17.74% Cl.

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

M and / or R melting point CC) the acid used 4-C1 165-166 horses. HCl, CF ₃ cooh 3,4-Cl 216-221 cf ₃ cooh 2-C1 156-157 cf ₃ cooh 4-OCF ₃ 143-145 cf ₃ cooh

176

M and / or R melting point (CC) the acid used 4-OF ₃ 179-180 CF 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 horses. HC1 4-SO ₂ CH ₃ 221 to 221.5 cf ₃ cooh 3,4-F 173 to 175.5 cf ₃ cooh 3-CF ₃ 166-168 cf ₃ cooh 4-COOCH ₃ 155.5 to 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 a solution of 2- (p-chlorophenyl) pyrrole-3-carbonitrile (16.83 g, 83.1 mmol) in glacial acetic acid (450 mL) was added dropwise 14.7 mL (24 mL) at 36 ° C over 18 min. 70 g (183.0 mmol) of sulfuryl chloride. During the addition, there will be a slight exothermic reaction associated with a temperature rise to 39'C. After a further 16 minutes, the reaction mixture is filtered under vacuum and the solid material is washed first with acetic acid and then with water. This solid melts after recrystallization from hot ethyl acetate at 259-261 ° C.

178

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

IR (nujole suspension) V _max : 3170 (bs), 3100 (m), 2225 (s), 1508 (m), 1097 (M), 835 (s), 717 (m), 660 (m) cm ^{- 1} .

N-NMR (dimethylsulfoxide, δ 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, δ values): 136.01 (C ₂ pyrrole, 133.92 (c ₄ p-chlorophenyl), 129.09 (carbons at positions 3 and 5 of chlorophenyl), 127.41 (C ₄ p (Chlorophenyl) 127.11 (C 1-4 p-chlorophenyl), 114.49 (nitrile carbon), 114.10 (C ₅ pyrrole), 110.92 (C ₄ pyrrole), 90.09 (C ₃ pyrrole) .

Microanalysis (MW 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, with a melting point above 230'C, is a single component according to thin layer chromatography (a mixture of equal parts of ethyl acetate and hexane).

180

Analysis for: ^C 12 ^H 5 ^Br 2 ^F 3 ^N 2 calculated 36.55% C, 1.27% H, 7.11% N, 40.61% Br; Found: C, 36.40, H, 1.08, N, 6.99, Br.

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

L M R X Y melting point CC) 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

$ Fô

354ί · -4- »χ • k: vji

- 181 .. .... ';

L M R X Y melting point (CC) H 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 H H 4-OCF ₃ br br H H 4-OCF ₃ Cl H H H 4-CN br br > 230 H H 4-CN Cl Cl > 240 H H 4-SO ₂ CH ₃ br br > 230 H H 4-NO ₂ Cl Cl 246-249 H 3-C1 4-C1 br br > 260 H H 3-CF ₃ Cl Cl > 230 H H 4-COCH ₃ Cl Cl 251-254 H 2,3 CH = CH Cl Cl 244-247 H H _4-CH3 Cl Cl 215-217 H 2-C1 4-C1 br br > 230 H H 3-C1 Cl Cl > 230 H 2-C1 4-C1 Cl Cl > 230

182

L M R X Y melting point CC) H H 4-C1 br Br · 273-274 H H 2-C1 br br > 230 H H 4-CF3 Cl Cl > 230 H H 4-Br Cl Cl > 235 H H 2-C1 Cl Cl > 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

183

5.7 g (0.0345 mol) of α-nitroacetophenone are taken up in 100 ml of toluene and 4.6 (0.0345 mol) of aminoacetaldehyde diethyl acetal is added to the solution. The reactants were introduced into a 4-liter round bottom flask equipped with a Dean-Stark trap. The box is filled with molecular sieves (4 x 10 &lt; ^{10 &gt;} m) and the mixture is heated under reflux for 18 hours. Evaporation of the toluene in vacuo afforded 8.36 g of .alpha .- (2,2-diethoxyethylamino) -p-nitrostyrene as a brown oil which was taken up in 50 ml of concentrated hydrochloric acid. When the flask was stirred in a circular motion, the oil turned into a yellow suspension. After 10 minutes the solid material was filtered off to give 2.48 g of a yellow solid which, after recrystallization from ether-ethyl acetate-hexane, gave the desired product in two fractions. Yield: 2.08 g (31%), m.p. 190 DEG-192 DEG.

184

IR _{ν max} : 1485 cm ^-1 (NO ₂ ).

H-NMR (CDCl3, dimethylsulfoxide, δ): 6.73 (m, 2H), 7.46 (m, 5H).

Further β-nitrostyrene derivatives can be prepared by the above-described reaction by substituting α-nitroacetophenone with an appropriately substituted α-nitroacetophenone and / or replacing the aminoacetaldehyde diethyl acetal with an appropriate 2,2-dialkoxyethylamine having 1 to 4 carbon atoms in each alkoxy group. The following compounds are obtained in this way.

Alk = alkyl of 1 to 4 carbon atoms

 ίόϊ. '' ΛΛ ·· .:

185

L M R (OA11c) ₂ H H p-ch ₃ oco (O0 ₂ H ₅ ) H p-ch ₃ H (oc ₂ h ₅ ) H _m-OCH3 p-och ₃ (0C ₂ h ₅ ) H / (OC ₂ H ₅ ) p-Cl \ H H (OCH ₃ ) ₂ H p-ch ₃ H (OCH ₃ ) ₂ H H p-cf ₃ (oc ₂ h ₅ ) 3-dichloro-4- nitro-5 Example 65 -fenylpyrol

186

To a mixture of 3-nitro-2-phenylpyrrole (1.56 g, 0.0083 mol) and dioxane (60 ml) was added dropwise 25.9 g (0.0182 mol) of commercial sodium hypochlorite under ice-cooling. The reaction mixture was stirred for 45 minutes, 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, after purification by chromatography on silica gel using a mixture of ethyl acetate and hexane with an increasing portion of ethyl acetate as eluents, yields 0.77 g (36%) of the resulting solid, m.p. 190-190.5. ° C

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

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

187

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 quality materials. The concentrations indicated are those of the active ingredient. All tests are performed at 27 ° C.

Test for Spodoptera eridania (3rd instar larvae)

The bean leaves of 7 to 8 cm in length 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 are then placed in petri dishes (100 x 10 mm) having a damp filter paper on the bottom, each containing 10 Spodoptera eridania larvae (3rd instar). After five days, the experiment is evaluated,

188, mortality, reduced feeding, and / or any disorder of normal larval development is detected.

Spodoptera eridania - residual effect (7 days)

Plants treated as described above are maintained in a greenhouse for 7 days under high intensity lamp illumination, which is twice the brightness of a bright sunny day in June in New Jersey, simulating a 14 hour day length. After seven days, the leaves of the plants are subjected to the test described above.

Aphis fabae

Dishes, each containing one capuchin crops (Tropaeolum sp.) Plant of about 5 cm in height, are infested with about 100 to 200 poppy aphid specimens one day prior to the start of the test. Each dish is then sprayed on a rotary table in a fume hood at a rotating speed of 4 rpm using a DeVilbis atomizer with the test composition. Spraying is performed over two rotations of the table. The sprayer nozzle is about 15 cm away from the plant

The 189 sprays aim to reach the entire plant and aphids. The treated dishes are placed on the side of the white enamel trays and held in this position for 2 days. Mortality is then evaluated.

Tetranychus urticae (phosphate mite)

One of the monthly bean plants grown in bowls is removed at a time when the primary leaves reach a length of 7-8 cm and one is removed from each bowl and the remaining are cut off. Small pieces are cut from the leaves of the infested plant and placed on each leaf of the test plant. This is done 2 hours before the treatment to allow the mite to disperse around the test plant and lay eggs. The size of the pieces of infested leaves varies so that about 100 mites per leaf of the test plant. When the test composition is applied, the pieces of leaf used for infection are removed and discarded. Plants infested with mites are immersed in the test composition under stirring for 3 seconds, then allowed to dry in a fume cupboard and maintained for 2 days before adult mortality is observed on the first sheet.

190

The second leaf is left on the plant for an additional 5 days, then the mortality of the eggs and / or the new nymphs is evaluated.

Diabrotica undecimpunctata howardi (3rd instar)

1 cm ^{3 of} finely ground talc is introduced into a wide-necked glass jar with screw cap and 1 ml of the respective acetone suspension of the test substance is pipetted in each case so that 1.25 or 0.25 mg of the active substance is contained in the container. introduces a gentle stream of air until acetone evaporates. The dried talc is spread and 1 cm ^{3 of} millet seeds (as feed for experimental insects) and 25 ml of moist soil are introduced into the container. The vessel is sealed and mixed thoroughly (Vortex mixer). Diabrotica undecimpunctata howardi larvae (3rd instar) are then introduced into each vessel and the vessels are loosely sealed to allow air entry for the larvae. Mortality is evaluated after six days. Missing larvae are considered dead because they decompose rapidly and their remains can be found. The concentrations of active ingredient used in this test correspond to about 50 and 10 kg / ha.

191 The results of the experiment shall be expressed by numbers and letters and the following meanings:

no effect

1 10 - 25% mortality 2 26 - 35% mortality 3 36 - 45% mortality 4 46 - 55% mortality 5 56 - 65% mortality 6 66 - 75% mortality 7 76 - 85% mortality 8 86 - 99% mortality

100% mortality

R lower ingestion

The results of the above tests are shown in the following overview.

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200

Example 67

Insecticidal activity tests

Heliothis virescens (3rd instar)

The cotton uterus leaves 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 piece of moistened dental swab. One larva (3rd instar) is then placed in each dish and the dish is covered with a cardboard lid. After 3 days, mortality and a decrease in the consumption are found.

Empoasca abrupta - adults

A 5 cm long bean leaf 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 (100 x 10 mm), which has a damp filter paper at the bottom, 10 adults of Empoasco are placed in each dish.

201 abrupts and the test is run for 3 days. After this time, mortality is determined.

Blatelle germanica (rus) - adult males (bait test)

1 ml of a 1000 ppm test compound solution was pipetted per 1 g of corn flour presented in a 30 ml wide neck flask to prepare a 0.1% bait composition. The bait is dried by introducing a gentle stream of air into the flask and then placed in a half-liter wide-necked bottle containing 10 adult Russian males. The bottle shall be covered with a lid of netting, on which a piece of cotton soaked with 10% honey shall be placed. Mortality was found after three days.

Blatella germanica (rus) - adult males (residual effect test)

Pipette 1 ml of 1000 ppm acetone solution of test substance slowly into the petri dish bottom (150 x 15 mm) so that the bottom of the dish is sparged as evenly as possible. After drying of the deposited material, 10 adult Russian males are placed in each dish and the dish is capped. Mortality is calculated after 3 days.

Spodoptera eridania (3rd instar larvae) - systemic efficacy

The test compound is made into an emulsion containing 0.1 g test substance, 0.2 g emulsifier (Emulphor EL-620), ml acetone and 90 ml water. This formulation 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. Monthly 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 the soil to rot during the test. The cut off plants were put into the test emulsions and wrapped with a piece of cotton wool that was kept some distance above the bottom of the bottle while preventing evaporation and runaway

203 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 taken 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 detrimental effect on the size of the loan are identified.

Empoasca abrupta - 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 EL-620), 10 ml of acetone and 90 ml of water. This formulation 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. Monthly bean plants whose primary leaves have already reached a length of 7 to 8 cm are cut at least 3 cm above the soil surface to prevent contamination with soil bacteria that could cause rotting during the test. The truncated plants are placed in the test emulsions and coated with a piece of cotton wool to keep them at a certain distance above the bottom of the bottle while preventing evaporation

204 and elution of 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 taken from the plant and placed in a Petri dish (100 x 10 mm) with 10 specimens of adult Spodoptera eridania. Mortality was found after 3 days

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

The results obtained are summarized in Table II below.

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SE - Spodoptera eridania - Blatella germanica

212

Example 68

A) Evaluation of test compounds as nematicidal agents

Maintaining culture

Caenorhabditis elegans (Bristol strain by J. Lewis) are maintained on Escherichia coli on agar plates at 20 ° C. Cultures are renewed weekly.

The nematodes used for the assay are eluted from 4 to 5 day old cultures using a modified Fresh Ascaris Ringers Solution (FARS). The worms were further washed with FARS containing gentamycin to suppress bacterial contamination and centrifuged to separate from the wash solution. This procedure was repeated three times. The washed worms are introduced into C. briggsae maintenance medium (C. brigssae Maintenance Medium - CbMM; GIBCO) to which gentamycin (600 units / ml) and mycostatin (0.5 mg / ml) were added.

To save the active substances and work, the tests are carried out with a mixture of three compounds selected on the basis of the results

213 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 μΐ) and the solvent allowed to evaporate. The plates thus treated are either immediately used or stored in the freezer without appreciable detrimental effects on the active compounds.

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

After 4, 24 and 48 hours, the efficiency is evaluated under a scanning microscope. Immediately before reading, it taps slightly into the plate to stimulate worm movement. Activity is assessed subjectively but semiquantitatively based on

214 effect of the test compound on the mobility of adults and larvae. The evaluation shall be carried out according to the following criteria:

= no movement = significantly reduced mobility at about 95% of worms = reduced mobility = slightly reduced mobility = normal mobility, the same as in the control experiment

Other factors indicative of efficacy are readily detectable. Examples include death, rigor mortis, contractions, coiling, paralysis, abnormal plucking, reduction of worm populations in 48 hours and other deviations from normal behavior.

Test Procedure for Caenorhabditis eleqans Day 0 * Inoculation of an E. coli agar plate 30 to specimens c. elegans * incubation at 20 ° C day 4 * isolation of new C. elegans population * antibiotic wash * transfer to CbMM

215 * dosage of the worm (25 to 100 μπι) to the wells with the test substance ^a) + observed activity at 4 hours * Day 5 Day 6 observed activity observed activity *

Note: ^(a ) wells with test substance may be prepared either immediately or in advance and stored in a freezer

The data found in this test are summarized in Table III below.

B) Effectiveness test against Meloidogyne incognita

Meloidogyne incognita nematode populations are maintained on greenhouse tomatoes (Fireball), eggs are taken from the roots of infested plants and laid on damp filter paper for 24 hours for hatching. The hatched larvae invade the water under the filter paper.

For the test, the larvae are transferred to wells in plates containing test compounds deposited as a 3% 300 ppm acetone flow. Approximately 10 larvae were 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 using 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- (α, α, α-9,9 trifluoro-p-tolyl) pyrrole-3-carbonitrile

4,5-dibromo-2- (α, α, α-9,9 trifluoro-p-tolyl) pyrrole-3-carbonitrile

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

218

test substance C. elegans 150 ppm larvae adults Meloidogyne incognita 300 ppm 2,3-dichloro-5- (p-chlorophenyl) -4-nitropyrrole 9 9 9 2,3-dichloro-5- (3,4-dichlorophenyl) -4nitropyrol 9 9 0 2- (p-bromophenyl) - 4,5-dichloro-3nitropyrol 9 9 6 2,3-Dichloro-4-nitro-5- (α, α, oncitluoro-p-tolyl) pyrrole 9 9

219

Example 69

Using the procedures described in Examples 66 and 67, the efficacy of the compounds of the invention is evaluated against various insects, 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. If two or more assays were performed on the same compound, averages were calculated from the results. A dash indicates that the assay was not performed in the present case.

220

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Claims (25)

PATENT CLAIMS 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 their natural habitat are contacted with an insecticidally, nematocidically or acaricidally effective amount of an arylpyrrole compound of formula I where X represents a hydrogen, fluorine, chlorine, bromine or iodine atom or a trifluoromethyl group; Y represents a fluorine, chlorine, bromine or iodine atom, a trifluoromethyl group or a cyano group; 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 halogens or one benzyloxy optionally substituted with one halogen, furthermore C 1 -C 4 alkoxycarbonylmethyl alkoxy, 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, dialkylaminocarbonyl having 1 to 4 alkyl moieties carbon atoms or cycloalkylaminocarbonyl having 4 to 6 carbon atoms in the cycloalkyl moiety; L is hydrogen, fluorine, chlorine or bromine; and M and R are each independently hydrogen, (C1-C3) alkyl, (C1-C3) alkoxy, (C1-C3) alkylthio, (C1-C3) alkylsulfinyl, (C1-C3) alkylsulfonyl; up to 3 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 in adjacent positions together with carbon atoms the 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; 250 R ¹ represents a hydrogen atom, a fluorine atom, a difluoromethyl group, a fluorochloromethyl group or a trifluoromethyl group; R ² is C 1 -C 3 alkyl, C 1 -C 3 alkyl 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 represents a hydrogen atom, an alkyl group having 1 to 3 carbon atoms or the radical R ⁵ CO; R ⁵ represents a hydrogen atom or a C 1 -C 3 alkyl group and n is a number of 0, 1 or 2. 2. A method according to claim 1, wherein the arylpyrrole compounds are those 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, 251 2,4-dibromo-5- (p-chlorophenyl) pyrrole-3-carbonitrile, 5- (p-chlorophenyl) 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 method of protecting growing plants from insect, nematode and mite infestation, characterized in that an insecticidally, nematocidally or acaricidally effective amount of an arylpyrrole compound as defined in claim 1 is applied to the leaves of the plants or to the soil or water in which they grow. . The method of claim 3, wherein the arylpyrrole compounds used are those selected from the group set forth in claim 2. The method according to claim 3, characterized in that the arylpyrrole compound as defined in claim 1 is applied to the plants or the soil in which the plants grow in an amount of 0.125 to 4.0 kg / ha. The method of 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 they grow, in the form of a liquid composition. 252 containing 10 to 10,000 ppm of an arylpyrrole compound as defined in claim 1. 7. An insecticidal, acaricidal and nematicidal composition, characterized in that it contains, as active ingredient, an arylpyrrole compound as defined in claim 1. 8. Insecticidal, acaricidal a. The nematicidal composition of claim 7, wherein the arylpyrrole compound is a compound selected from the group set forth in claim 2. Arylpyrrole compounds of the general formula I, wherein the individual symbols have the meaning given in claim 1, but X is not a hydrogen atom. 10. Arylpyrrole compounds according to claim 9, wherein A is hydrogen or (C1-C4) alkoxymethyl, W is cyano or nitro, XaY is 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, 253 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) -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. 12. A process for the preparation of arylpyrrole compounds generally means a hydrogen, chlorine or bromine atom; Y represents a chlorine or bromine atom; 254 represents a hydrogen atom; represents cyano or nitro, represents hydrogen, fluorine, chlorine or bromine and M and R are each independently hydrogen, (C1-C3) alkyl, (C1-C3) alkoxy, (C1-C3) alkylthio, (C1-C3) alkylsulfinyl, (C1-C3) alkylsulfonyl; up to 3 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 in adjacent positions together with carbon atoms the atoms to which they are attached may form a ring in which MR represents a residue Z is S (O) _n or oxygen; R ³ represents a hydrogen atom, a fluorine atom, a difluoromethyl group, a fluorochloromethyl group or a trifluoromethyl group; R ² is C 1 -C 3 alkyl, C 1 -C 3 alkyl or a radical NR ³ R ^4; • x R represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms; 255 R ⁴ represents a hydrogen atom, an alkyl group having 1 to 3 carbon atoms or the radical R ⁵ CO; R ⁵ represents a hydrogen atom or a C 1 -C 3 alkyl group and n is a number of 0, 1 or 2. characterized in that it is benzoylacetonitrile or α-nitroacetophenone corresponding to the general formula II C - _CH2 w in which L, M, R, and W are as _jyýznam ^ I shall, reacted at elevated temperature sV ^ ialkoxyetylamínom containing in each alkoxy 1 to 4 carbon atoms, to give N- (2,2-dialkoxyetylamino) -p-cyanostyrene or α (2,2-dialkoxyethylamino) -p-nitrostyrene, each containing from 1 to 4 carbon atoms in each alkoxy moiety and corresponding to the general formula in which Alk represents a C 1 -C 4 alkyl group 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. 13. The process of claim 12, wherein the reaction of the 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. Process according to Claim 12, characterized in that the intermediate α- (2,2-dialkoxyethylamino) -cyanostyrene or α- (2,2-dialkoxyethylamino) -β-nitrostyrene, containing in each case an alkoxy moiety of 1 to 2 4 carbon atoms, 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 N-CH _? CH (OAl) ₂ H in which Alk represents an alkyl group having 1 to 4 carbon atoms; means 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; up to 3 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 in adjacent positions together with carbon atoms the atoms to which they are attached may form a ring in which MR represents a residue -CH ₂ O-, -OCF ₂ O- or Z is S (O) _n or oxygen; η R represents a hydrogen atom, a fluorine atom, a difluoromethyl group, a fluorochloromethyl group or a trifluoromethyl group; R ² is C 1 -C 3 alkyl, C 1 -C 3 alkyl 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 represents a hydrogen atom, an alkyl group having 1 to 3 carbon atoms or the radical R ⁵ CO; R ⁵ represents a hydrogen atom or a C 1 -C 3 alkyl group; 258 n is a number with a value 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 wherein: X represents a hydrogen, chlorine or bromine atom; 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 by 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 by a C 1 -C 3 alkyl group carbon atoms, (C 1 -C 3) alkoxy or (C 1 -C 3) halogen, furthermore C 3 -C 4 alkenyl optionally substituted by C 1 - 3 halogen atoms, or C 3 -C 4 alkynyl; L is hydrogen, fluorine, chlorine or bromine; and M and R are each independently hydrogen, (C1-C3) -alkyl, (C1-C3) -alkoxy, (C1-C3) -alkylthio, (C1-C3) -alkylsulfinyl, (C1-C3) -alkylsulfonyl; from 1 to 3 carbon atoms, cyano, F, Cl, Br or I, a nitro group, a trifluoromethyl group, a radical of formula R CFjZ, R ² CO or NR ³ R ^4, or M and R, bound on adjacent positions together with the carbon atoms to which they are attached may form a ring in which MR represents a residue Z is S (O) _n or oxygen; η R represents a hydrogen atom, a fluorine atom, a difluoromethyl group, a fluorochloromethyl group or a trifluoromethyl group; R ² is C 1 -C 3 alkyl, C 1 -C 3 alkyl 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 represents a hydrogen atom, an alkyl group having 1 to 3 carbon atoms or the radical R ⁵ CO; r 5 represents a hydrogen atom or a C 1 -C 3 alkyl group; and n is a number with a value of 0, 1, or 2. 260 17. The method of claim 16, wherein the arylpyrrole compounds are 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; and 2.3-dichloro-5- (3,4-dichlorophenyl) -4-nitropyrrole. 18. A process according to claim 3, wherein the arylpyrrole compounds of formula I are those of formula Ia as defined in claim 16. 19. The method of claim 18 wherein the arylpyrrole compounds used are those 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 the soil in which the plants grow at a rate of 0.125-4.0 kg / ha. Insecticidal, acaricidal and nematicidal composition, characterized in that it contains an arylpyrrole compound as defined in claim 16 as active substance. The composition of claim 21, which is in the form of a liquid, wherein the content of the arylpyrrole compound of claim 16 is in the range of 10 to 10,000 ppm. 261 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 each general symbol is as defined in claim 16, but X is not a hydrogen atom and when W is nitro and A is methyl then Y is bromo or M and R are different from 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-nitro-pyrrol.