HU204971B - Insecticidal, acaricidal and nematocidal compositions comprising arylpyrrole derivatives as active ingredient and process for producing arylpyrrole derivatives - Google Patents

Description

The present invention relates to an insecticidal, acaricidal and nematicidal agent containing an arylpyrrole derivative as an active ingredient, and to a process for the preparation of arylpyrrole slides.

The novel arylpyrrole derivatives can be represented by the formula (I) wherein X is chloro, bromo or iodo or trifluoromethyl;

Y is chloro, bromo or iodo, and trifluoromethyl or cyano,

W is cyano or nitro,

A is hydrogen, (C 1 -C 4) alkyl optionally substituted with halogen, hydroxy, (C 1 -C 4) alkoxy or (C 1 -C 4) alkylthio, phenyl, phenoxy or (C 1 -C 2) alkoxy-phenyl; C4 -C4alkylmethyl, C3-4alkyl optionally substituted by halogen, Cyano, C3-4alkynyl optionally substituted by halogen, or alkyl moieties thereof

C 1-4 dialkylaminocarbonyl,

L is hydrogen, fluorine, chlorine or bromine,

Me and R are each independently hydrogen, (C 1 -C 3) alkyl, (C 1 -C 3) alkoxy, (C 1 -C 3) alkylsulfonyl, cyano, fluoro, bromo or iodo, nitro, trifluoromethyl, R ₁ CF ₂ Z or R _{2 is} CO, or the adjacent M and R, together with the carbon atom to which they are attached, form a ring in which MR is a)

Z stands for oxygen,

R 1 is fluoro or CHF ₂ ,

R ₂ is C 1-3 alkyl.

Preferred examples of the novel arylpyrrole derivatives are represented by formula (II)

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

Another group of preferred representatives of the novel arylpyrrole derivatives is represented by formula (III):

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

A further group of preferred representatives of the novel arylpyrrole slides is represented by Formula IV, wherein

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

A further group of preferred representatives of the novel arylpyrrole derivatives is represented by formula (V) wherein

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

A further group of preferred representatives of the novel arylpyrrole derivatives is represented by formulas VI and VII, wherein

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

Preferred are arylpyrrole derivatives of the formula (I) wherein

THE is hydrogen or C 1-4 5 alkoxymethyl group, W is cyano or nitro, L is hydrogen or fluorine, X and Y taken is chlorine or bromine or trifluoromethyl, 10M is hydrogen, fluorine, chlorine or bromine, R represents a fluorine, chlorine or bromine atom and a trifluoromethyl or trifluoromethoxy group.

Preferred are compounds of formula (Π) wherein

A is hydrogen or C 1-4 alkoxymethyl,

L is hydrogen, 1 M is hydrogen, fluorine, chlorine or bromine,

R is a fluorine, chlorine or bromine atom and a trifluoromethyl or trifluoromethoxy group,

W is cyano,

X and Y are each independently chlorine, bromine or trifluoromethyl. Particularly potent insecticidal, acaricidal and / or nematicidal compounds are those compounds of formula (H) wherein A is hydrogen or (C 1 -C 4) alkoxymethyl;

L is hydrogen,

M is hydrogen, fluorine, chlorine or bromine,

R is fluorine, chlorine or bromine as well as trifluoromethyl or trifluoromethoxy,

W is nitro,

X and Y are each independently chlorine, bromine or trifluoromethyl.

Examples of novel arylpyrrole compounds include the following:

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

4.5-dichloro-2- [p-trifluoromethoxy-phenyl] -pinole-3-carbonitrile,

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

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

4.5-dichloro-2- (o-chlorophenyl) -piaole-3-carbonitrile,

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

4.5-dichloro-2- (a, a, a-t'-fluoro-p-tolyl) -pyrrole-3-carbonitrile,

4.5-dibromo-2- (a, a, a-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-3-carbonitrile,

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

2- (p-bromophenyl) -4,5-dichloro-3-nitro-pyrrole,

HU 204,971 Β

2.3-dichloro-4-nitro-5- (a, a, a-trifluoro-p-tolyl) pyrrole,

4.5-dichloro-2- (m-chlorophenyl) -piaole-3-carbonitrile,

4.5-dichloro-2- (p-chlorophenyl) pyrrole-3-carbonitrile,

4.5-dichloro-2-phenylpyrrole-3-carbonitrile,

2.3-dichloro-5- (p-chlorophenyl) -4-nitropyrrole,

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

2.3-dibromo-5- (p-chlorophenyl) -4-nitropyrazole,

2.3-dichloro-4-nitro-5-phenylpyrrole,

3-Bromo-2-chloro-4-nitro-5- (a, a, a-trifluoro-p-tolyl) pyrrole, 5-chloro-2- (3,4-dichlorophenyl) -1- (methoxy) -methyl) -4- (trifluoromethyl) pyrrole-3-carbonitrile,

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

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-chloro-phenyl) -l- (2-propynyl) -4,5-bis (trifluoromethyl) pyrrole-3-carbonitrile,

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

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

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

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

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

2-chloro-5- (3,5-dichlorophenyl) -4-nitro-pyrrole-3-karbonttril,

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

2.4-dibromo-5-phenylpyrrole-3-carbonitrile,

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

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

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

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

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

5- (2-Bromo-5-ethyl-phenyl) -2,4-bis (trifluoromethyl) -pyrrole-3-carbonitrile, 1-ethyl-2- (p-fluorophenyl) -4-nitro-3,5 bis (trifluoromethyl) pyrrole,

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) piaole-2,3-dicarbonitrile,

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

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

5-chloro-2- (3,4-dibromophenyl) -l-methyl-4-nitro-pyrrole-3-carbonitrile,

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

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

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,

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

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

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

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

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

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

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

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

2.3-dibromo-4- (p-chlorophenyl) -pinO1-5-carbonitrile,

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

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

4-bromo-3- (p-chlorophenyl) -l-methyl-thiomethyl-5- (trifluoromethyl) -pircol-2-carbonitrile,

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

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

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

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

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

3-Bromo-5-chloro-4- (p-chlorophenyl) -2-nitropyrrole, 1-cyano-3- (3,4-dibromophenyl) -5-nitro-2- (trifluoromethyl) ) pyrrole,

3-bromo-l-methoxymethyl-4- (m-trifluoromethylphenyl) -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-methoxy-phenyl) -5-nitro-2,4-di- (trifluoromethyl) pyrrole,

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

4-Chloro-3- (p-chlorophenyl) -1- (isopropyloxycarbonylmethyl) -5-nitropyrrole-2-carbonitrile, 3- (o-bromophenyl) -4- (trifluoromethyl) methyl) -pircoI-2,5-di-carbonitrile,

HU 204971 Β 1-methyl-4- [3,5-di (trifluoromethyl) phenyl] -pinOl-2,3-dicarbonitrile,

4- (m-bromophenyl) -l-methyl-5-carbomethoxy-chloro-pirral2,3-dicarbonitrile,

4- (p-chlorophenyl) -l- (2,2,2-trifluoro-ethyl) -5- (trifluoromethyl) -pimoI-2,3-dicarbonitrile,

4- (3,5-dichloro-phenyl) -2-nitro-5- (trifluoromethyl) -piiTol-3-carbonitrile,

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

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

2-bromo-3- (3,4-dichlorophenyl) -1-ethylthiomethyl-4-nitro-5-trifluoromethylpyrrole,

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

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

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

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

3- (4-Bromo-3-methyl-phenyl) -5-chloro-4-nitro-pyrrole-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-nitropyrrole, 2- (3,5-dibromo-4-methoxyphenyl) -4,5-dichloropyrrole-3-carbonitrile,

2.3-dichloro-4-nitro-5- (2,4,6-trifluorophenyl) pyrrole,

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

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

2.3-Dichloro-4-nitro-5- [p- (trifluoromethoxy) phenyl] -polyTol ₁

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.

It can be used according to the invention and in its alkoxy moieties

C 1 -C 4 α- (2, 2-diacyloxyethylamino) -p-cyanostyrene and α- (2, 2-dialkoxyethylamino) - 4-nitrostyrene compounds are represented by formula (IX). wherein

W is cyano or nitro,

L is hydrogen, fluorine, chlorine or bromine,

Me and R are each independently hydrogen, (C 1 -C 3) alkyl, (C 1 -C 3) alkoxy, (C 1 -C 3) alkylsulfonyl, cyano, fluoro, bromo or iodo, nitro, trifluoromethyl, R ₂ CF 3, R ₂ CO or two adjacent M and R together with the carbon atom to which they are attached form a ring in which MR is a group of formula (a),

Z is oxygen,

R 1 is fluoro, CHF ₂ ,

R ₂ is C 1-3 alkyl.

Preferred are the β-substituted styrene compounds having the formula

W is cyano,

L is hydrogen, chlorine or bromine,

M is hydrogen, fluorine, chlorine or bromine or methoxy,

R is hydrogen, fluoro, chloro or bromo, trifluoromethyl, nitro, trifluoromethoxy, or methoxy, or adjacent M and R together with the carbon atom to which they are attached form a ring in which MR is (a) .

Further preferred are β-substituted styrene compounds wherein W is nitro,

L is hydrogen, chlorine or bromine,

M is hydrogen, fluoro, chloro or bromo, or methoxy,

R is hydrogen, fluoro, chloro or bromo, trifluoromethyl, nitro, trifluoromethoxy or methoxy, or adjacent M and R together with the carbon atom to which they are attached form a ring wherein MR is A the above β-cyano-styrene and β-nitro-styrene compounds may also be referred to as dialkyl acetals.

Preferred dialkyl acetal compounds include:

(E) and (Z) (1) p-Chloro-N - [(methynylmethyl) amino] -cinnammonitrile diethyl acetal, (2 - [(methynylmethyl) amino] -3,4-dimethoxy -cinnamonite 40 x 1 -dimethoxy-acetal, (3) (Z) -methyl-p- (2-cyano-1 - [(formylmethyl) amino] vinyl) benzoate diethyl acetal, (4) (Z) N - [(formylmethyl) amino] -1-naphthaleneacrylonitrile diethyl acetal, (5) (Z) -P - [(formylmethyl) amino] -p-methylcinnarnonitrile diethyl acetal, (6) N- (Formylmethyl) p-methyl, α- (nitromethylene) benzylamine diethyl acetal, (7) N- (Formylmethyl) -3,4-dimethoxy, α- (nitromethylene). ) 50 benzylamine diethyl acetal, (8) N- (formylmethyl) -a- (nitromethylene) -2-naphthalenemethylamine diethyl acetal, (9) methyl p- (α - [(formanylmethyl) ) -amino] - p -nitrovinyl) benzoate -? - (diethylacetal), (10) N- (formylmethyl) -3,4-dimethoxy-a- (nitromethylene) benzylamine-dimethylacetal , (11) (E) and (Z) p-chloro-N - [(formylmethyl) amino] cinnamonitrile dimethylacetal, (N 2 - [(formylmethyl) amino] -3,4- dimethoxycinnamoyl nitrile dimethyl acetal,

(20) p-trifluoromethyl-3 - [(formylmethyl) -amino] - (13) 3,4-dichloro - [(formylmethyl) amino] -cinnamonitrile diethyl acetal; cinnamonitrile diethyl acetal.

The β-cyano-styrene compounds, also referred to as cinnammonitrile dialkyl acetal, may be prepared by reacting substituted or unsubstituted benzoyl acetonitrile with a C 1 -C 4 2,2-dialkoxyethylamine in the presence of an aromatic solvent. The C4-aromatic substituted α- (2,2-όΪ3ΐ1 <οχΐ-βΐίΙ-3ΠΊΪηο) -β-cyano-styrene is formed which is converted into the phenyl-substituted 2-phenylpyrrole-3-carbonitrile in its phenyl moiety. The resulting cyanophenylpyrrole compound is chlorinated with sodium hypochlorite or sulfuryl chloride in an inert solvent to give the phenyl-substituted 4,5-dichloro-2-phenylpyrrole-3-carbonitrile having insecticidal, acaricidal and nematicidal activity. The intermediate from the paper can also be prepared with concentrated hydrogen chloride at a temperature of 20-40 ° C. The reaction is illustrated in Scheme A, wherein

A is hydrogen, (C 1 -C 4) alkyl optionally substituted by (C 1 -C 4) alkoxy, (C 1 -C 4) alkylthio, halo, or (C 1 -C 4) alkoxy, (C 3 -C 4) alkenyl, which is optionally substituted with a halogen atom or a C3-4 alkynyl group,

X is chlorine or bromine,

Rg is C1-C4 alkyl,

L, R and M are as defined above.

The arylpyrrole derivatives of formula (I) wherein A is hydrogen and W is cyano can be prepared when N-formyl-DL-phenylglycine or substituted N-formylphenylglycine of formula (VIII) wherein

L is hydrogen, fluorine, chlorine or bromine,

R and M are each independently hydrogen, (C 1 -C 3) alkyl, (C 1 -C 3) alkoxy, (C 1 -C 3) alkylsulfonyl, cyano, fluoro, bromo or iodo, nitro, trifluoromethyl, R ₁ CF ₂ Z or R _{2 is} CO, or adjacent R and M together with the carbon atom to which they are attached form a ring in which MR is a group of formula (a),

Z is oxygen,

R [is fluorine, CHF _2] ,

R ² is C 1-3 alkyl, reacted with at least one equivalent of 2-chloroacrylonitrile and 2-3 equivalents of acetic anhydride. The reaction is carried out at an elevated temperature, preferably about 70100 ° C. The reaction is illustrated in Scheme B.

The resulting phenyl optionally substituted 2-phenylpyrrole-3-carbonitrile can be readily converted to the corresponding 4-halo, 5-halo or 4,5-dihalo-2-phenylpyrrole-3-carbonitrile of the general formula (II) 2-phenylpyrrole-3-carbonitrile is reacted with at least one or two equivalents of sulfuryl halide, bromine or chlorine in the presence of a solvent such as dioxane, tetrahydrofuran, acetic acid or chlorinated hydrocarbon. Monohalopyrrole-3-carbonitrile requires about one equivalent of a halogenating agent, while dihalopyrrole-3-carbonitrile requires two to three equivalents of the halogenating agent. When sulfuryl chloride or sulfuryl bromide is used as the halogenating agent, the reaction is usually carried out at a temperature below about 40 ° C, preferably between 0 and 30 ° C, while the reaction temperature for elemental bromine is about 3040 ° C. Sodium hypochlorite, tert-butyl hypochlorite, N-bromosuccinimide, N-iodosuccinimide and the like can also be used as halogenating agents for the above reaction. The reaction is illustrated in Scheme C.

The carbonitrile compounds of formula (II) may also be prepared by reacting an optionally substituted benzoylacetonitrile with a C1-C4-2,2-dialkoxyethylamine in its alkoxy moiety in the presence of an aromatic solvent, substituted in its alkoxy moiety with a C1-C4 and aromatic moiety. - (2,2-Dialkoxyethylamino) - 4-cyano-styrene is formed with trifluoroacetic acid or concentrated hydrogen chloride at a temperature in the range of about 20-40 ° C to give the desired phenyl-substituted 2-phenylpyrrole-3- to carbonitrile. The reaction is illustrated in Scheme D, where

R ₆ is C 1-4 alkyl,

L, R and M are as defined above.

The 3-nitro-2-phenylpyrrole derivatives of formula (II) optionally substituted in the phenyl moiety of the present invention can be prepared by reacting an optionally substituted α-nitroacetophenone with a C1-C4-2,2-dialkoxyethylamine in the alkoxy moiety. The reaction is generally carried out in the presence of an inert organic solvent, preferably an aromatic solvent, at an elevated temperature to form in its alkoxy moiety α-(2,2-dialkoxyethylamino) -3-nitro-styrene optionally substituted with 1 to 4 carbon atoms and an aromatic moiety. by treatment with a mineral acid such as hydrochloric acid or hydrobromic acid in its phenyl moiety to form an optionally substituted 3-nitro-2-phenylpyrrole of formula II. When the nitrophenylpyrrole derivative so prepared is reacted with sodium hypochlorite at low temperature in an inert organic solvent, the phenyl moiety is optionally substituted with a compound of formula II

2,3-dichloro-4-nitro-5-phenylpyrrole is obtained. The reaction is illustrated in Scheme E.

Surprisingly, it has been found that the optionally substituted benzoylacetonitrile derivatives can be prepared by a variety of processes described in the literature by appropriately substituted benzoyl halide with an alkali metal hydride and an alkyl cyanoacetate such as tert-butyl cyanoacetate in benzoyl. optionally substituted tert-butylbenzoyl cyanoacetate. The reaction is illustrated in Scheme F.

HU 204971 Β

The cyanoacetate ester thus obtained can be converted to the corresponding optionally substituted benzoylacetonitrile by heating in p-toluenesulfonic acid containing toluene. The reaction is illustrated in Scheme G.

Examples of tert-butyl cyanoacetate derivatives prepared according to Scheme F include the following:

L M R Mp. (° C) H 3-C1 4-C1 91-94 H H 4-OCF ₃ 81-84 H H 4-Br 113-115 H H 4-CF3 146-147 H H 4-F 98-100 H H 4-CN 127-128 H H 4-CH ₃ SO ₂ 127-129 H 3-F 4-F 91-94 H H 4- CHF ₂ CF ₂ O 92-94 3-C1 5-C1 4-CH3O -

Examples of benzoylacetonitrile derivatives prepared according to Scheme G include the following:

1 ^L M R Mp (° C) H H 4-Cl 128.5-129.5 H 3-Cl 4-Cl 105-107 H H 2-C 153-155 H H 4-OCF3 79 -81 H H 4-CF3 44 -45 H 2-C1 4-C1 66 -67 H H 3-Cl 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-CF3 58 -60 H H 4-CH3 103.5 to 106 H H 4-NO ₂ 119-124 3-C1 5-C1 4-OCH3 -

N-substituted arylpyrrole derivatives of formula (I) may be prepared by providing a corresponding substituted arylpyrrole derivative of formula (I) wherein

A is hydrogen, and

L, M, R, W, X and Y are reacted with the appropriate alkylating agent as above in the presence of a base. Suitable examples are brominated C 1-4 hydroxyalkyl compounds and potassium tert-butoxide. The reaction gives an arylpyrrole derivative which has the same substituent as the starting material and additionally has a C 1-4 hydroxyalkyl group on its nitrogen atom. By using cyanogen bromide instead of the brominated hydroxyalkyl compound, the aryl10 pyrrole derivative of the formula (I) bearing a carbonitrile group on its nitrogen atom is obtained. The reaction is illustrated in Scheme H, where

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

A is C 1-4 alcohol in one case and cyano in the other.

2-phenylpyrrole-3,4-dicarbonitrile, 2-bio-5-phenylpyrrole-3,4-dicarbonitrile and substituted phenyl. derivatives thereof may be prepared by reacting fumaronitrile with bromine in the presence of a chlorinated hydrocarbon such as chloroform at an elevated temperature to give bromofumaronitrile. This is reacted with N- (trimethylsilyl) methyl-5-methylbenzothioimidate or a substituted derivative thereof in the presence of hexamethylphosphoramide at an elevated temperature to give 2-phenylpyrrole-3,4-dicarbonitrile. The thus obtained 3,4-dicarbonitrile derivative is brominated to give 2-bromo-5-phenylpyrrole-3,4-dicarbonitrile or its phenyl-substituted derivative when the N-trimethylsilylmethyl-5 methyl methyl benzothioimidate was used. The reaction is illustrated in Scheme 30.

Other methods for preparing the novel compounds are also illustrated in the examples.

The novel arylpyrrole derivatives can be used to control insects, mites and nematodes. The compounds may also be used to protect the developing or harvested crop.

In practice, in general, about 10 to 10,000 ppm, preferably 100 to 5,000 ppm, of the arylpyrrole derivative of formula (I) are used which encompasses all (Π), (ΠΙ), (IV), (V), (VI) and (VH). dispersed in water or other readily available liquid carrier for treating a crop, a crop, or a soil for growing a crop. The active ingredients can also be used to treat lawns against various diseases such as larvae and insects.

The arylpyrrole derivatives of the formula (I) can also be used against insects, nematodes and mites by treating the soil or water used for growing foliage and / or plants, which usually involves

0.125 to 4.0 kg / ha of active compound is applied. Of course, higher application rates can be used, but this usually does not lead to additional effects.

Although the novel arylpyrrole derivatives are effective on their own against insects, nematodes and mites, other biologically active substances such as further insecticides, nematicides and acaricides may be incorporated into the compositions of the present invention. The novel arylpyrrole derivatives may be combined, for example, with phosphates, carbamates, pyrethroids, formamidines, chlorinated

Genes, halobenzoyl ureas and the like. °

The 2-aryl-3-cyano-4,5-dihalopyrrole derivatives of β-cyano-styrene compounds are useful in the control of insects, mites and nematodes. These compounds can also be used to protect emerging or harvested crops from the above pests.

In practice, the halogenated arylpyrrole derivatives are generally used in dispersions in an amount of about 10 to 10,000 ppm, preferably 100 to 5,000 ppm, in water or other readily available liquid carrier for treating the crop, the crop or the soil for growing the crop.

The halogenated arylpyrrole derivatives can also be used against insects, nematodes and mites by treating the foliage and / or soil or water for growing the plant. Halogenated arylpyrrole derivatives are generally applied in an amount of 0.125 to 4.0 kg / ha. Of course, higher application rates can be used, but this does not lead to additional effects.

The arylpyrrole derivatives are preferably used in the form of dry granules, liquid formulations, granulate formulations, wettable powders, emulsifiable concentrates, powders, powder concentrates, microemulsions and the like, which can be used to treat soil, water and / or foliage. For the preparation of the compositions, the active ingredient is mixed with an inert, pharmaceutically acceptable solid or liquid carrier.

For example, wettable powders, powders, and powder concentrate formulations may be prepared by co-milling 3-20 wt.% Of the arylpyrrole derivative of formula I with about 3 to 20 wt. Suitable anionic surfactants are, for example, sodium sulfosuccinic acid dioctyl ester, such as Aerosol OTB from American Cyanamid Company. About 60-94% by weight of solid solids such as montmorrillonite, attapulgite, limestone, kaolin, talc, diatomaceous earth, chalk, silicates and the like are used.

Granules are used primarily for treating soil or water. It can be prepared by co-grinding an equal amount of arylpyrrole derivative, generally about 3 to 20 parts by weight, and solid surfactant with about 60 to 94% by weight of gypsum. The mixture is then converted to a small particle size of about 0.3-0.6 mm. Nonionic block copolymers such as ethylene oxide and propylene oxide polymers may be used as solid surfactants in addition to the anionic sodium sulfosuccinic acid dioctyl ester, preferably BASF Wyandotte Corporation Pluronic 10R8,17R8,25R8, F38, F68, F77 or F87.

In addition to the powder and concentrate formulations described, water-dispersible wettable powders and liquid formulations are preferred. These compositions are preferably applied to the leaves of the plant or to the breeding or feeding environment of the pests.

When the compositions of the present invention are used in combination with other pesticidal agents, the application may be in the form of a mixture, or may be carried out sequentially in a separate composition.

Similarly, a liquid arylpyrrole containing composition in combination with other pesticides may be used as a tank mix or sprayed separately. The liquid composition according to the invention preferably contains from 0.001 to 0.1% by weight of the active ingredient.

The invention is further illustrated by the following examples.

/. example

2-Phenyl-pyrrole-3-carbonyltril

The procedure used is the same as that described in JOC 43, 4273-6 (1978). 30.00 g of N-formylphenylglycine were stirred at 90 ° C for 1.5 hours with a magnetic stirrer. The clear yellow solution was concentrated in vacuo to give 42.5 g of a bama-orange oily solid. This material was purified by chromatography on silica gel. The product was found to be a mixture of 73% by weight of 2-phenylpyrrole-3-carbonitrile and 27% by weight of 2-phenyl-3-cyano-5-methylpyrrole by 1 H NMR. Recrystallization from chloroform once and twice from 1,2-dichloroethane gave 1.69 g of a white solid, m.p. 148-152 ° C, 96% by weight, by 1 H NMR.

Elemental Analysis (MW 168.19): Calculated: C78.55, H4.79, N16.66; Found: C78.52, H4.73, N16.54.

Example 2

4,5-Dichloro-2-phenyl-pyrrole-3-carbonitrile and 5-chloro-2-phenyl-pyrrole-3-carbonitrile

A solution of 2-phenyl-3-cyanopyrrole (2.00 g, 11.9 mmol) in methylene chloride (80 mL) was stirred with a magnetic stirrer and cooled in ice water. Sulfuryl chloride (1.90 mL, 3.19 g, 23.6 mmol) was added dropwise via syringe over 5 min. Temperature during addition

5-10 ° C. The mixture was stirred at this temperature for 90 minutes. Filtration in vacuo gave 1.28 g of 5-chloro-2-phenylpyrrole-3-carbonitrile, m.p. 192.5-195 ° C. The filtrate was diluted with ethyl acetate (400 mL), washed with water (2 x 200 mL), dried over sodium sulfate, treated with charcoal, filtered and concentrated in vacuo. The residue was triturated with hexane to give 0.60 g (21.3%) of a pink solid. This was recrystallized from hot acetone (5 mL) to give 0.32 g (9%) of 4,5-dichloro-2-phenylpyrrole-3-carbonitrile as an orange-brown solid, m.p. 254-255 ° C.

IR (nujol): 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 (DMSO): δ - 7.73 (d, J-6.6 Hz, 1.97 H, 2 phenyl H at C-2.6), 7.52 (t, J-7.3 Hz, 2.04H, 2 phenyl

HU 204971 Β

H at C-3.5), 7.44 (t, J-7.3, 3Hz, 1.02H, 1 phenyl at H-C-4).

C-NMR (DMSO): δ-137.51 (C-2 from red to C), 129.25 (C-4 phenyl C), 129.04 (C-3.5 phenyl C), 128.37 (C- 1 phenyl C), 125, C8 (C-2.6 phenyl C), 114.32 (C-5 purine C or nitrile C), 114.14 (C-5 purine C or nitrile C), 110.72 (From C-4 to C), 89.78 (from C-3 to C).

Elemental analysis (237.09):

Calculated for C 55.72% H 2.55% N 11.02% Cl 29.91% Found C 55.78% H 2.59% N11.12% Cl 29.74%. 10

Example 3 p-Chloro-N - [(formylmethyl) amino] cinnammonitrile diethyl acetal

250.00 g (1.39 mol) of p-chlorobenzoylacetonitrile and 15

A solution of 2,23-diethoxyethylamine (203 mL, 185.95 g, 1.39 mol) in dry toluene (1300 mL) was stirred at reflux for 20 hours with magnetic stirring. The resulting water was collected with a Dean-Stark separator (23.8 mL, 95.2% theoretical - 20a). The hot brownish solution containing a large amount of solid precipitate was filtered through diatomaceous earth. It was diluted with 200 mL of ethyl acetate and filtered through a 7 x 13.5 cm column filled with silica gel. The filtrate was concentrated in vacuo to give 354.38 g (crude yield 86.4%) as a clear dark oil which slowly solidified. The solid was recrystallized from hot cyclohexane to give 324.26 g (79.1%) of a waxy orange solid. NMR showed 78% Z and 23% E ρ-10Γ-β - [(--0Γ-30 millimethyl) amino] cinnamonitrile diethyl acetal, m.p. 60-72 ° C. The following analytical data were taken from another sample prepared in the same way.

Irish (Nujol): 3325 (s), 3065 (m), 2197 (s), 1600 (s), 1530 35 (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 = 7.47 (d, J = 8.6 Hz, 2.12 H, 2 aromatic H), 7.37 (d, J = 8.6 Hz, 2.12 H, 2 aromatic H), 40 5.10 (E) and 4.86 (Z) (broad t, 1.25 H, one NH), 4.69 (Z) and 4.60 (E) (t, J = 5.1 Hz, 1.05 H, one methine-H on the acetal carbon), 4.07 (E) and 4.05 (Z) (s, 0.83 H, enamine beta-H), 3.71 ( E) and 3.68 (Z) (q, J = 7.1 Hz,

2.22 H, 2 methylene H at one of the 2 ethoxy groups), 3.56 45 (Z) and 3.53 (E) (q, J = 7.1 Hz, 2.22 H, 2 methylene H at one of the 2 ethoxy groups , 3.18 (t, J = 5.1 Hz, 1.77 H 2 methylene H on the ethylene acetal group), 1.20 (t, J = 7.1 Hz, 4.90 H, 6 methyl H on ethoxy 2).

C-NMR (chloroform): δ-161.21 (alpha-enamine C), δ 136.29 (Z) and 134.60 (E) (C-1 or C-4 phenyl C),

134.08 (Z) and 132.30 (E) (C-1 or C-4 phenyl C),

129.34 (Z) and 129.89 (E) (C-2.6 or C-3.5 phenyl C), 128.94 (Z) 128.63 (E) (C-2.6 or C- 3.5 phenyl C), 121.19 (Z) and 119.50 (E) (nitrile C), 99.43 (Z) and 55 100.63 (E) (beta-enamine C), 61.88 ( Z) and 63.25 (E) (methine C on the acetal group), 62.64 (Z) and 63.03 (E) (methylene on the ethoxy group), 46.32 (Z) and 47.33 (E) (methylene ethylamine), 15.26 (methyl on ethoxy). 60

Elemental analysis (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

To 108 ml of trifluoroacetic acid was added 54.00 g (0.183 mol) of solid p-chloro-β- (formylmethyl) amino] cinnamonitrile diethyl acetal under stirring at 23 ° C over 45 minutes. The exotherm causes the reaction mixture to warm to 38 ° C during the addition and a solid precipitate forms after 32 minutes. After stirring for 30 minutes at room temperature, the mixture was filtered under vacuum and the collected solid washed first with trifluoroacetic acid, second with ethyl acetate / hexane and finally with hexane. 16.83 g (45.4%) of a white solid are obtained, m.p. 165-166 ° C. The following analytical data were taken from another sample prepared in the same way.

IR (nujol): 3275 (br, s), 2225 (s), 1502 (s), 1410 (m), 1275 (m), 1200 (s), 1023 (m), 999 (m), 908 (m) )

843 (s), 752 (s), 722 (s), 695 (s), 620 (s) cm ^-1 . 1 H-NMR (acetone): δ-11.22 (v, broad s, 0.99 Η, 1 pair NH), 7.82 (d, J = 8.9 Hz, 2.46 H, 2 aromatic phenyl H) ), 7.51 (d, J = 8.9 Hz, 2.46 Hz, 2 aromatic phenyl H), 7.02 (t, J = 2.6 Hz, 1.01 Η, 1 pair H C-5 ), 6.58 (t, J-2.6 Hz, 0.77 Η, 1 pair at H C-4).

C-NMR (acetone): δ 137.73 (pinrol C-2), 134.42 (chlorophenyl at C-4), 129.93 (methine at C-phenyl C-3.5), 128, 07 (methine at phenyl C-2.6), 121.21 (red at C-5), 117.93 (nitrile C), 113.78 (red at C C-4), 90.86 (pinol at C at C-3).

Elemental Analysis (202.64):

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

The following compounds of formula (X) (wherein W is cyano and L is hydrogen) can be prepared as described or by using concentrated hydrochloric acid instead of trifluoroacetic acid:

M and / or R Mp. (° C) Applied acid 4-C1 165-166 cc. HClCF 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-CF ₃ 179-180 CF ₃ COOH 2,4-Cl 197-199 cf ₃ cooh 3-Cl 150-156 cf ₃ cooh 4-CN 210 -212 CF ₃ COOH 4-F 167-170 cc. HC1 4-SO ₂ CH ₃ 221-2221.5 CF ₃ COOH 3,4-di-F 173-175.5 cf ₃ cooh 3-CF ₃ 166-168 cf ₃ cooh

HU 204,971 Β

M and / or R Op. ('C) Applied acid 4-COOCH3 155.5 to 158 CF3COOH 4-CH3 117-137 CF3COOH 4-NO ₂ 174-177 CF3COOH

Example 5

4,5-Didoro-2- (p-chlorophenyl) pyrrole-3-carbonitrile 16.83 g (83.1 mmol) of 2- (p-chlorophenyl) pyrrole-3-carbonitrile in 450 ml 14.7 ml (24.70 g, 183.0 mmol) of sulfuryl chloride are added dropwise over 18 minutes at 36 ° C to a solution of glacial acetic acid and stirred in a mechanical stirrer. During the exotherm, the reaction mixture was heated to 39 ° C during the addition, and after 16 minutes the mixture was filtered under vacuum. The solid was washed first with acetic acid and then with water. Recrystallization from phosphorus ethyl acetate gives a solid, m.p. 259-261 ° C. The following analytical data were taken from another sample prepared in the same way.

IR (Nujol): 3170 (br s), 3100 (m), 2225 (s), 1508 (m), 1097 (m), 825 (s), 717 (m), 660 (m) ^cm-1 H- NMR (DMSO): δ = 7.72 (d, J = 8.6 Hz, 2.00 H, 2 aromatic H), 7.56 (d, J = 8.6 Hz, 2.00 H, 2 aromatic H) ). C-NMR (DMSO): δ = 136.01 (red C-2), 133.92 (p-chlorophenyl C-3.5), 129.09 (p-chlorophenyl C-3.5), 127 , 41 (p-chlorophenyl C-4), 127.11 (p-chlorophenyl Cl), 114.49 (nitrile C), 114.10 (red C-5), 110.92 (pyrrole C- 4), 90.09 (C-3 from red).

Elemental Analysis (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

4J-Dibromo-2- (a, a, a-trifluoro-p-tolyl) pyrrole-3-carbonyl tryl

To a solution of 0.8 g of 2- (a, a, a-trifluoro-p-tolyl) pyrrole-3-carbonitrile in 70 ml of chloroform was added 2 ml of bromine with stirring. The reaction mixture was stirred overnight and the resulting white solid was filtered. TLC (ethyl acetate / hexane 1: 1) shows the product to be a spot with a melting point above 230 ° C.

Elemental Analysis 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% Η 1.08% N 6.99 % Br 40.55%.

In the same manner as in Examples 5 and 6, but using 2- (a, α, α-trifluoro-p-tolyl) -pinyl-3-carbonitrile, the appropriately substituted phenylpyrrole-3-carbonitrile can be prepared as follows: ):

L M R X Y Op. ('C) H H 4-NO ₂ Br Br 274-277 H H 4-F cl cl > 220

L M R X Y Op. ('C) 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-Cl 3-Cl 4-C1 cl cl 2-Br 3-Br 4-Br Br Br H H 4-OCF3 cl cl 222-225 H H 4-OCF3 Br Br 231-232 H H 4-OCF3 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-CF3 cl cl > 230 H H 4-COCH3 cl cl 251-254 H 2,3-CH = CH- cl cl 244-247 H H 4-CH3 cl cl 215-217 H 2-Cl 4-C1 Br Br > 230 H H 4-C1 cl cl 255-257 H H 4-0 Br Br 273-274 H H 2-Cl Br Br > 230 H H 4-CF3 cl cl > 230 H H 4-Br. cl cl > 235 H H 2-Cl cl cl > 230 H 3-Cl 4-C1 cl cl > 235 H H H cl cl 254-255 H H 3-Cl cl cl > 230 H 2-Cl 4-C1 cl cl > 230 H H 4-CF3 Br Br > 230 H H 4-C1 cl Br 262-263 (Dec) H H 4-C1 Br cl 250-258 (Dec) H 3-Cl 5-Cl cl cl > 230 H 3-Cl 4-Cl cl Br > 230 2-Cl 4-C1 5-F cl cl 207-210

Example 7

3-Nitro! phenyl-pyrrole

Alpha-nitroacetophenone (5.7 g, 0.0345 mol) was taken up in toluene (100 mL) and aminoacetaldehyde diethyl acetal (4.6 g, 0.0345 mol) was added. The reaction mixture was poured into a 250 mL flask and connected to a Dean-Stark plug. A 4A molecular weight filter was added and the mixture was refluxed for 18 hours. Removal of toluene in vacuo gave 8.36 g of (2,2-diethoxyethylamino) -3-nitrostyrene as a brown solid.

EN 204971 Β in the form of oil. To this was added 50 ml of concentrated hydrochloric acid. Upon mixing, the oil becomes a yellow suspension. After 10 minutes, the solid was filtered off to give 2.48 g of a pale solid. Recrystallization from ether (ethyl acetate) hexane gave 2.08 g (31%) of product in two fractions, m.p. 190-192 ° C.

ZR: MSmcm-'NOa)

1 H-NMR (CDCl 3 / DMSO): δ = 6.73 (m, 2H), 7.46 (m,

5H).

Example 8

23-Dichloro-4-nitro-5-phenylpyrrole

A mixture of 3-nitro-2-phenylpyrrole (1.56 g, 0.0083 mol) in dioxane (60 ml) was cooled in an ice bath and 25.9 g (0.0182 mol) of sodium hypochlorite were added.

The mixture was stirred for 45 minutes and then acidified with concentrated hydrochloric acid. Dilute with water and ethyl ether. The layers were separated and the upper organic layer was washed with water, dried over anhydrous magnesium sulfate (20 ') and evaporated in vacuo. The resulting solid (2.21 g) was purified by chromatography on silica gel eluting with increasing ethyl acetate / hexane. 0.77 g (36%) of a yellow solid is obtained, m.p. 190-190.5 ° C. 25

Elemental analysis: Ο ₁₀ Η ₆ Ν ₂ Ο ₂ α ₂ Calculated: C 46.72% H2.35% N 10.90% Found C 46.96% H286% N 10.02%.

In the same manner as in Examples 7 and 8, but with the appropriately substituted alpha-nitroacetophenone and its alkoxy moiety.

Using C 1 -C 4 2,2-dialkoxyethylamine gives (2,2-dialkoxyethylanuno) -P-nitro-styrene which is treated with hydrochloric acid, hydrobromic acid or trifluoroacetic acid to give 3-nitro-2-phenyl to a pyrrole. This is reacted with sodium hypochlorite in dioxane to give the corresponding chloro derivative, and in chloroform with bromine to give the corresponding bromo derivative. The following compounds of formula (XH) may be prepared:

L M R X Y Mp. (° C) H H H cl cl 190-190.5 H 4-Cl H cl cl 214-215 H 4-Cl H Br Br 203-204 (decomposes) H H H Br Br 148.5-149 3-Cl 4-Cl C cl cl 219-220 (decomposes) H 4-Br H cl cl 222 -223 (decomposes) H H 4-CF ₃ cl cl 166-168

Example 9

4,5-Dichloro-2- (3,4-dichloro-phenyl) -l-methyl-pyrrole-3-carbonitrile

To a brown solution of 2 g of 4,5-dichloro-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile (2 g) in dry tetrahydrofuran (60 ml) was added 1 molar equivalent of potassium tert-butoxide. The mixture is stirred for a few minutes to give a clear solution, to which is added a molar equivalent of methyl iodide via syringe. The mixture was refluxed for 4 hours and then stirred at room temperature overnight. Water (50 mL) was then added and extracted with chloroform (4 x 50 mL). The organic layers were combined, dried over magnesium sulfate and evaporated. The resulting solid was purified on silica gel eluting with ethyl acetate / hexane 1: 1. 1.80 g of a white solid are obtained. Yield: 86%. 154-156 ° C,

As described above, but using appropriately substituted phenylpyrrole-3-carbonitrile or 3-nitro-2-phenylpyrrole instead of 4,5-dichloro-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile the compounds of the formula (ΧΠΙ) can be prepared:

THE L M R X Y Op. ('C) ch ₃ H H 4-Cl cl cl 152-153 c ₂ h ₅ och ₂ H 3-Cl 4-Cl cl cl 128-130 C ₂ H ₅ H 3-Cl 4-Cl cl cl 137-138 ch ₃ H 3-Cl 4-Cl cl cl 154-156 ch ₃ H H 4-CF ₃ Br Br 145-146 C 6 H ₅ -CH ₂ H H 4-CF ₃ Br Br 145-147 C 6 H ₅ -CH ₂ H 3-C1 4-Cl cl cl 95-96 ch ₂ «ch-ch ₂ H 3-Cl 4-Cl cl cl 69-70 ch ₂ = c-ch ₂ 1 Cl H 3-Cl 4-Cl cl cl 147-148

HU 204,971 Β

THE L M R X Y Op. ('C) CH ₃ SCH ₂ H 3-Cl 4-Cl cl cl C (CH ₃ ) 3 H H 4-CF ₃ cl cl ch ₃ H H 4-CF ₃ cl cl 99-100 ch ₃ sc ₂ h ₅ H 3-C1 4-Cl cl cl 74-75 c ₂ h ₅ -ooc-ch ₂ H 3-Cl 4-Cl cl cl 118-120 c ₂ h ₅ -och ₂ H H 4-OCH ₃ Br Br 112-115 ch ₃ H H 4-Cl Br Br 197-201 c ₂ h ₅ och ₂ H H 4-OCF ₃ cl cl 46-47 ch ₃ H H 4-OCF ₃ cl cl 72-73 C 6 H ₅ -CH ₂ H H 4-OCF ₃ cl cl oil c ₂ h ₅ och ₂ H H 4-Cl cl cl - hoch ₂ ch ₂ H 3-Cl 4-Cl cl cl 143-145 NC H 3-Cl 4-Cl cl cl 251-252 C ₆ H ₅ CH ₂ OCH ₂ H 3-Cl 4-Cl cl cl 88-89 cio-ch ₂ H 3-Cl 4-Cl cl cl 118-120 ic = c-ch ₂ H 3-Cl 4-Cl cl cl 115-116 ch ₃ H H 4-Cl Br cf ₃ 126-129 c ₂ h ₅ och ₂ H H 4-Cl Br cf ₃ 91-92 C ₂ H ₅ -OCH ₂ H 3-Cl 4-Cl cl cl 118-120 c ₂ h ₅ -och ₂ H H 4-Cl Br Br 104-105 C 6 H ₅ -CH ₂ H H 4-Cl Br Br 81-82 ch ₃ H H 4-Cl Br Br 197-201 CN H H 4-CF ₃ cl cl 138-139 C ₂ H ₅ -OCH ₂ H H 4-CF ₃ Br cf ₃ 104-105 c ₂ h ₅ -och ₂ H H 4-CF ₃ H cf ₃ 76-77 c ₂ h ₅ och ₂ H 3-Cl 4-Cl Br cf ₃ 80-81

Example 10 1-Benzthi-4,5-dibromo-2 - (& alpha, a, a-trifluoro-p-tolyl) pyrrole-3-carbonitrile

In a 100 mL flask, 1.5 g of 4,5-dibromo-2- (a, a, atrifluoro-p-tolyl) pyrrole-3-carbonitrile was combined with 50 mL of dry tetrahydrofuran to give a clear dark solution. To this is added 1 molar equivalent of potassium tert-butoxide via syringe. After a few minutes, a clear solution was obtained, to which 0.65 g of benzyl bromide was added via syringe. The mixture is refluxed overnight and the starting material and product are examined by thin layer chromatography (ethyl acetate / hexane 1: 1). The reaction mixture is worked up as follows:

diluted with water (4 ml) and extracted with chloroform (4 x 50 ml). The organic layers were combined and washed four times with 50 ml of 10% w / w aqueous sodium hydroxide. The organic layer was dried over magnesium sulfate and evaporated. This gave a brown solid which was recrystallized from ethyl acetate / hexane. Yield: 0.75 g, 40.7%. Mp 145-147 ° C (dec.).

//. example

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

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) of potassium. tert -butoxide was added followed by 0.312 g (0.0033 mol) of chloromethylethyl ether. The reaction mixture was stirred at room temperature for about 1 hour and then poured into a large volume of water. The precipitated white solid was filtered and dried. 1.0 g (91%) of product are obtained. 128-130 ° C.

Example 12

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

To a solution of 17.87 g (88.2 mmol, 1.00 equivalents) of 2- (p-chlorophenyl) -3-cyanopyrrole in 800 ml of dioxane was added dropwise 250.15 g (purely 13.13 g) at 20 ° C with stirring. (176.4 mmol, 2.00 equivalents) of 5.25% bleach is added over 30 minutes. The mixture was stirred for an additional 30 minutes at room temperature and then to 2200 ml of water

HU 204971 Β pour. The resulting mixture was filtered under vacuum to remove a small amount of black solid. The filtrate is adjusted to pH 2 with concentrated hydrochloric acid, the precipitated brown solid is filtered off with suction and washed with water. 22.41 g of a brown solid are obtained. This is largely dissolved in 100 ml of 5% aqueous sodium hydroxide solution, leaving a small amount of insoluble black solid. This was dissolved in ethyl acetate (100 mL), washed with 5% aqueous sodium hydroxide solution (75 mL), water (75 mL), and saturated aqueous sodium chloride (75 mL). The ethyl acetate layer was dried over magnesium sulfate, treated with charcoal, filtered and concentrated in a rotary evaporator. 1.10 g (5.3%) of an orange-brown solid are obtained. This was recrystallized from ethyl acetate / chloroform to give 0.51 g (2.4%) of a white solid, 4-Chloro-3-cyano-2- (p-chlorophenyl) pyrrole. Melting point 251-253.5 ° C.

Example 13

5-Bromo-2- (3,4-dichloro-phenyl) pyrrole-3-carbonitrile

2- (3,4-Dichlorophenyl) pyrrole-3-carbonitrile (2.0 g, 0.008 mol) was dissolved in dioxane (100 mL) and heated at 40-50 ° C. The solution was cooled to 30 ° C and bromine (1.3 g, 0.008 mol) was added. After stirring for 1 hour at room temperature, the mixture was poured into water and the precipitated gray solid (2.2 g, 88%) was filtered. M.p. 233-236 ° C (dec.).

Starting from 2- (3,4-dichlorophenyl) -3-nitropyrrole, 5-bromo-2- (3,4-dichlorophenyl) 3-nitropyrrole can be prepared in the same manner.

Example 14

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

5-Bromo-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile (0.158 g, 0.005 mol) was dissolved in tetrahydrofuran (5 ml). An equivalent amount of tert-butyl hypochlorite was added and the solution was stirred overnight. The reaction mixture was poured into water and the precipitate (0.052 g, 30%) was filtered. Melting point above 275 ° C.

Starting from 2-bromo-5- (3,4-dichlorophenyl) -4-nitropyrrole, 2-bromo-3-chloro-5- (3,4-dichlorophenyl) -4-nitro- pyrrole.

Example 75

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

To a solution of 4-chloro-2- (chlorophenyl) pyrrole-3-carbonitrile (0.17 g, 0.67 mmol, 1.00 equiv.) In chloroform (100 mL) was stirred at 22 ° C for 30 min. A solution of bromine (0.62 g, 3.88 mmol, 5.79 equivalents) in chloroform (5 mL) was added dropwise. The dosage is not exothermic. The reaction mixture was stirred at room temperature for 3.25 hours and the pure red reaction mixture was evaporated in vacuo. 0.28 g of a white solid is obtained, which is suspended in hexane / methylene chloride and filtered under vacuum. 0.23 g of white fluff is obtained. 262263 ° C (dec.).

Example 16

5-Chloro-4-bromo-2- (p-chlorophenyl) pyrrole-3-carbonitrile 1.00 g (4.22 mol, 1.00 equivalents) 5-chloro-2- (p-chlorophenyl) - To a solution of pyrrole-3-carbonitrile in 300 ml of chloroform was added dropwise a solution of 0.40 ml (1.24 g, 7.76 mmol, 1.84 equivalents) of bromine in 25 ml of chloroform with stirring at 45 ° C for 30 minutes. The addition is not exothermic and a small amount of solid precipitate forms at the end of the addition. The reaction mixture

After stirring at room temperature for 19.5 hours, it was concentrated in vacuo. The resulting orange-white solid (1.49 g) was suspended in hexane / methylene chloride and filtered under vacuum. 1.33 g (100%) of a white fluffy solid are obtained. M.p. 250-258 ° C (dec.).

Example 17

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

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 stirring for 5 minutes was added 0.75 ml ( Sulfuryl chloride (1.26 g, 9.34 mmol, 0.79 equivalent) was added dropwise. About 5 minutes after the addition is complete, a solid precipitate begins to form. After stirring for 45 minutes at room temperature, the mixture was filtered and the precipitate washed thoroughly with cold acetic acid. This gave 2.08 g (74% crude yield) of a white solid which was recrystallized from 75 ml of hot acetic acid. 1.63 g (58%) of the product is 97% pure. Melting point 258.5-261 ° C.

Example 18

2- (3,4-Dichlorophenyl) -I-methylpyrrole-3-carbonitrile

To a solution of 2.0 g of 2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile (2.0 g) in dry tetrahydrofuran (50 ml) was added an equivalent of potassium tert-butoxide. Pipette one equivalent of methyl iodide into the slightly opaque solution. This gives a slightly luminous solution. A drying tube was attached to the flask and the reaction mixture was stirred overnight at room temperature. A light colored precipitate forms at the bottom of the flask. Water (50 mL) was added to the reaction mixture to give a clear solution which slowly precipitated out a solid. This was filtered and analyzed by thin layer chromatography (25% ethyl acetate in hexane) as compared to the starting material. The product gives a single spot that moves faster than its starting material. The product was dried under vacuum at 50 ° C overnight. 1.31 g (62%) of product are obtained. Melting point 140-142 ° C.

Example 19

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

In a 20 mL 971 Β mL round bottom flask, 0.5 g of 2- (3,4-dichlorophenyl) 1-methylpyrrole-3-carbonitrile was mixed with 35 mL of glacial acetic acid. The mixture was heated slowly until completely dissolved. Two equivalents of sulfuryl chloride are added to the clear solution by pipette. The solution was stirred at room temperature for 12 hours. The reaction mixture was poured into water (50 mL) and the white precipitate was filtered and dried under vacuum at 50 ° C for 3 hours. The resulting solid was identical to the product of Example 9 by TLC (25% EtOAc in hexane) and infrared. Yield 0.36 g (56%).

Example 20

4.5- Dichloro-2- (3,4-dichloro-phenyl) -1- (2-hydroxy-ethyl) -pyrrole-2-carbonitrile

2.0 g (6.5 mmol) of 4,5-dichloro-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile and 0.88 g (7.8 mmol) of potassium tert-butoxide are added. The mixture was stirred under reflux and 0.98 g (7.8 mmol) of bromoethanol was added. The mixture was stirred at reflux for 12 hours, cooled, diluted with water (50 mL) and extracted several times with chloroform. The combined chloroform extracts were dried over magnesium sulfate and concentrated in vacuo. The resulting solid precipitates from the starting blend by heating, dissolving in ethyl acetate and cooling. The mother liquor was evaporated and the residue was recrystallized from 20% ethyl acetate in hexane to give 0.31 g of a white solid. Melting point 143-145 ° C.

IR: 5077A.

Elemental 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 27

4.5-Dichloro-2- (3,4-dichlorophenyl) pyrrole-1,3-dicarbonitrile

Potassium tert-butoxide (617 mg, 55 mmol) was added portionwise to a solution of 3-cyano-4,5-dichloro-2- (3,4-dichlorophenyl) pyrrole (1.52 g, 5 mmol) in dry tetrahydrofuran (20 mL). After 30 minutes, a solution of cyanobromide (583 mg, 5.5 mmol) in tetrahydrofuran (1 mL) was added. The reaction mixture was allowed to stand at room temperature overnight and the solvent was removed on a rotary evaporator. The residue was treated with water and extracted with ethyl acetate. The organic layer was washed with water and saturated sodium chloride solution and dried over magnesium sulfate. The residue is evaporated and the residue is recrystallized from ethyl acetate. 1.07 g of white crystals are obtained. Melting point: 250.5-252.0 ° C.

IR (nujol): 2255.2245 cm ^-1 (CN).

¹³ C-NMR (DMSO-d ₆ ): 102.7 (N-CN), 113.7 (3-CN),

Mass Spec: 331.9 (M + 1).

Elemental analysis based on C ₁₂ H ₃ Cl ₄ N ₃ (330.99):

H, 0.91; N, 12.70; Cl, 42.85. Found: C, 43.62; H, 0.93; N, 12.63; Cl, 41.95.

Example 22

4,5-Dichloro-2- (3,4-dichloro-phenyl) -l- (3-iodo-2-propynyl) pyrrole-3-carbonitrile

To a solution of 1.91 g (5.5 mmol) of 4,5-dichloro-2- (3,4-dichlorophenyl) -1 (2-propynyl) -pyrrole-3-carbonitrile in 500 mL of methanol was stirred 69 mL of Aqueous sodium hydroxide (w / w) was added followed by 0.70 g (2.7 mmol) of iodine. The reaction mixture was stirred for 12 hours, then acidified and diluted with water (200 mL). The precipitate was filtered off and recrystallized from methanol. 0.51 g of white crystals is obtained. 115-166 ° C.

The above reaction can be used to convert any substituted N-alkynyl arylpyrrole of formula (III), (IV), (V), (VI) or (VII) to an N-substituted 3-iodo-2-propynylarylpyrrole.

Example 23

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

5.7 g (0.0254 mol) of N-iodosuccinimide are slowly added to a solution of 3.0 g (0.0127 mol) of 2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile in 100 ml of tetrahydrofuran. The reaction mixture was stirred for several hours at 25 ° C until TLC (silica gel, ether / petroleum ether / acetic acid 100: 100: 1) to confirm completion. The reaction mixture was then concentrated in vacuo to give a residue containing pyrrole and succinimide. The crude solid was dissolved in ether (500 mL) and extracted with water (5 x 400 mL) to remove succinimide. The ether was dried over sodium sulfate and concentrated in vacuo. This gave 2.0 g (32.3%) of a gray-brown solid. Melting point above 230 ° C (a red vapor is formed).

Example 24

2-Phenyl-1-pyrrole-4-carbonitrile

A solution of acrylonitrile (0.65 mL, 0.01 mol) and N-trimethylsilylmethyl-S-methylbenzene thioimidate (2.4 g, 0.01 mol) in tetrahydrofuran (100 mL) was treated with an ice / acetone bath. Cool to -5 ° C. Under nitrogen, 1.0 ml of a 1N solution of tetrabutylammonium fluoride in tetrahydrofuran and 20 ml of tetrahydrofuran are added dropwise over 30 minutes. The reaction mixture was stirred for an additional 30 minutes at -5 ° C and then allowed to warm slowly to room temperature. After stirring for a further 18 hours, the solvent was removed under reduced pressure. The residue was partitioned between ether / water and the aqueous layer was extracted with fresh ether. The combined organic layers were washed with water and then with saturated sodium chloride solution. It was dried over magnesium sulfate and the filtrate was cooled. This gave a white solid (1.2 g, 70% yield), which was identical to that of Tsuge (J. Org. Chem. 52, 2523 [1987]).

Analysis for C _h H ₁₀ N ₂ requires: C 77.65% H 5.88% N 16.47% Found: C 77.55% H5,83% N 16.39%.

HU 204971 Β

Example 25

2-Phenylpyrrole-4-carbonitrile Under nitrogen, 0.23 g (0.001 mole) of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone and 0.17 g (0.001 mole) of 2-phenyl-1. pyrroline-4-carbonitrile and 13 ml of 1,2-dimethoxyethane were dissolved. To the resulting orange solution was added in one portion 0.08 mL (0.001 mol) of pyridine, which was slightly exothermic (up to 28 ° C) and an immediate greenish-gray precipitate formed. The slurry was stirred at room temperature for 18 hours while most of the solvent was evaporated. The brownish solid was partitioned between ether and semi-saturated sodium carbonate solution. The reddish brown aqueous phase was extracted twice with ether and the combined ether layers were washed with fresh water and then with saturated sodium chloride solution. It was dried over magnesium sulfate and concentrated under reduced pressure. The resulting white semi-solid was recrystallized from dichloromethane to give 0.1 g of a lavender crystal.

The same product was condensed with alpha-chloroacrylonitrile and N- (trimethylsilyl) methyl-5-methylbenzene thioimidate with tetrabutylammonium fluoride catalyst (2-phenyl-1-pinroline-4 carbonitrile can be prepared directly in one step as described above). 155-158 ° C. 25

Elemental analysis C H _{N g,} N ₂ Calc'd: C, 78.57% H4,76% N Calculated 16.67% Found C 78.65% H4,70% N 16.43%.

Example 26 30

2,4-Dibromo-5-phenyl-pyrrole-3-karboniJril

Under nitrogen, a solution of bromine (0.6 mL, 0.012 mol) in chloroform (5 mL) was added dropwise to a stirred solution of 2-phenylpyrrole-4-carbonitrile (0.84 g, 0.05 mol) in chloroform (20 mL). The resulting solution 35 was stirred at room temperature for 18 hours and then the solvent was removed under reduced pressure. The resulting solid was recrystallized from C ₂ H ₄ Cl ₂ . 0.6 g of product is obtained. M.p. 239-242 ° C. 40

Analysis for C _u H ₆ Br ₂ N _2: Calcd C40,49% Hl 84% Br49,08% N8,59% Found C 39.88% Hl 87% B 48.81% N8,48%.

24-26. 2,4-Dibromo-5- (p-chlorophenyl) pyrrole-3-carbonitrile can be prepared as described in Example 1b. Melting point 45-270-272 ° C (dec.).

Example 27

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

To a mixture of 0.64 g (26 mmol) of magnesium turnings in 10 ml of tetrahydrofuran was stirred at 25 ° C in a 100 ml three-necked round-bottomed flask, equipped with a thermometer, 60 ml addition funnel and nitrogen inlet, 4.7 g (dropwise). A mixture of 2- (2-bromoethyl) -1,3-dioxolane (26 mmol) in tetrahydrofuran (40 mL) was added. The addition rate is adjusted so that the reaction temperature is below 50 ° C. The reaction mixture was then stirred at 25 ° C for 1 hour. Potassium 3,4-dichlorobenzoate (5.0 g, 22 mmol) was added in tetrahydrofuran (120 mL) under a nitrogen atmosphere. Quickly decant the unreacted magnesium bead from the Grignard solution and add dropwise to the potassium benzoate suspension with vigorous stirring. After stirring for 24 hours at 25 ° C, 50 ml of diethyl ether and 15 ml of 3N hydrochloric acid are added and the phases are separated. The organic layer was washed neutral with saturated aqueous sodium bicarbonate solution and rinsed with brine (10 mL). It was dried over sodium sulfate and concentrated in a rotary evaporator. The resulting beige semi-solid was purified by chromatography on silica gel with hexane / ethyl acetate 3: 1. This gave 4.3 g (60%) of ketoacetate as a white solid. Melting point: 115-117 ° C.

Example 28

3- (3,4-Dichlorobenzoyl) -propionaldehyde 3 g of 4 ', 4'-dichloro-3- (1,3-dioxolan-2-yl) propiophenone (10 g, 26 mmol) was added in 0.2 ml (0.2 mol). / 1 oxalic acid (0.9 g of oxalic acid hydrate dissolved in 30 ml of water) and 5 ml of ethanol. The mixture is refluxed for one hour and then allowed to cool. Most of the ethanol was removed in a rotary evaporator and the residue was treated with diethyl ether (100 mL) and saturated aqueous sodium bicarbonate (20 mL). The phases are separated and the organic phase is dried over magnesium sulfate. The rotary evaporator gave a viscous yellow oil which was chromatographed on silica gel with hexane / ethyl acetate 3: 1. so

6.3 g (75%) of ketoaldehyde are obtained in the form of a white solid.

Example 29

A suspension of 2- (3,4-dichlorophenyl) pyrrole (6 g, 26 mmol) in 3- (3,4-dichlorobenzoyl) propionaldehyde in 60 ml of absolute ethanol gave 4 g (52 mmol) of ammonium acetate. . The reaction mixture is refluxed for 20 minutes and then allowed to cool. The major mass of ethanol was removed in a rotary evaporator and the residue was mixed with dichloromethane / diethyl ether 1: 1 (200 mL) and water (50 mL). The phases are separated and the organic phase is dried over sodium sulfate. The rotary evaporator gave a dark brown oil which was chromatographed on silica gel with 3: 1 mixture. 4.6 g (83%) of pyrrole are obtained in the form of a light brown solid. Melting point 49-51 ° C.

Example 30

5- (3,4-Dichlorophenyl) pyrrole-2-carboxaldehyde In a round-bottom flask was added phosphorus oxychloride (0.6 mL, 6.5 mmol) dropwise via a syringe under stirring to 10 mL dimethylformamide. The solution turns pale yellow on heating. After stirring for 20 minutes, 2- (3,4-dichlorophenyl) pyrrole (1 g, 4.7 mmol) was added portionwise. The beige suspension was stirred for 30 minutes and then heated to 50 ° C for 40 minutes. To the cooled reaction mixture was added a solution of 10 g (122 mmol) of sodium acetate in 15 mL of water.

Add and stir for 20 minutes. The beige precipitate was filtered off and dried for 20 hours. so

1.1 g (95%) of substantially pure aldehyde were obtained. Melting point above 200 ° C.

Example 31

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

To a suspension of 1.5 g (6.2 mmol) of 5- (3,4-dichlorophenyl) pyrrole-2-carboxaldehyde in 20 mL of water and 20 mL of ethanol was added 0.7 g (6.2 mmol) of hydroxylamine-sulfonic acid. The reaction mixture was heated under reflux for 1 hour to give a gray precipitate. Allow to cool and then filter to give 1.5 g (99%) of substantially pure nitrile as a solid. Melting point 170-171 ° C.

Example 32

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

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) dropwise under nitrogen. . After stirring for 30 minutes at 25 ° C, water (10 ml) and diethyl ether (40 ml) were added. The phases are separated and the organic phase is dried over sodium sulfate. Concentrate in a rotary evaporator and chromatograph the residue on silica gel with hexane / ethyl acetate 3: 1. 0.5 g (60%) of dibromopyrrole are obtained in the form of a brown solid. Melting point above 250 ° C.

Example 33

4-phenyl-pyrrole-3-carbonitrile

To a mixture of 5.0 g (39 mmol) of cinnamonitrile and 7.6 g (39 mmol) of (p-tolylsulfonyl) methyl isocyanide in 30 mL of dimethyl sulfoxide and 65 mL of ether was added 1.86 g of 60% by weight over 20 minutes. A suspension of an aqueous sodium hydride suspension (1.11 g, 46 mmol) in ether (80 mL) was added. The reaction mixture was allowed to stand under nitrogen for 1 hour and then diluted with ether and water. The ether layer was separated, dried over magnesium sulfate and concentrated in vacuo. The resulting oil was chromatographed on silica gel with chloroform / ethyl acetate 1: 1 to give 2.5 g of a cream solid. This was recrystallized from ether / hexane to give 1.15 g of product. 123-125 ° C, NMRM86-1077.

References: Tetrahedron Letters 5337 (1972);

128-129 ° C.

Example 34

2.5-Dichloro-4-phenylpyrrole-3-carbonitrile

A solution of 4-phenylpyrrole-3-carbonitrile (0.66 g, 3.9 mmol) in dry tetrahydrofuran (20 mL) cooled to 6 ° C with stirring over a period of 4 minutes was treated with 0.66 mL (1.11 g, 8.2) sulfuryl chloride was added. After a further 45 minutes at 510 ° C, the mixture was stirred for 30 minutes to remove the ice bath. The reaction mixture was poured into a mixture of ethyl acetate (80 mL) and water (40 mL), the organic phase was separated, washed with water and dried over sodium sulfate. It was filtered through a short column packed with silica gel rinsed with ethyl acetate and the filtrate evaporated in vacuo. 0.95 g of a dark solid is obtained, which is recrystallized from chloroform. Yield: 0.42 g of white crystals, m.p. 195-196 ° C (dec.).

Analysis for C ₂ F _u HgCi from _2: Calcd: 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%.

The compounds of formula XIV can be prepared as described in Examples 33 and 34. The procedure for the preparation of 2,6-dibromo-4- (chlorophenyl) pyrrole-3-carbonitrile was the same as in Example 33 using bromine and dioxane instead of sulfuryl chloride and tetrahydrofuran.

R X Y Mp (° C) 4-C1 cl cl 237-240 (Dec) 4-CH ₃ cl cl 103-206 4-C1 Br Br > 245

Example 35

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

To a mixture of 5.63 g of a 60% w / w oily sodium hydride / oil slurry in 200 ml of dry ether were added, under a nitrogen funnel, 23.5 g (122 mmol) of ethyl p-chlorocinnamate and 19.4 g (122 mmol) ( A solution of p-tolylsulfonyl) methyl isocyanide in 180 mL of ether and 80 mL of dimethyl sulfonide was added. The dosing time is approx. 20 minutes and causes slight reflux. After stirring for a further 10 minutes, the mixture was diluted with water (100 mL), extracted four times with ether, the ethereal phases were dried over magnesium sulfate and concentrated in vacuo. The resulting solid was recrystallized from ethylene chloride to give 7.8 g of crystals. 137-138 ° C.

Analysis for C ₁₃ H ₁₂ C1NO _2: Calcd: C 62.53% H 4.81% N 5.61% Cl 14.23% Found: C 61.31% H 5.12% N 5.32% Cl, 14.57%.

Evaporation of the mother liquor from the crystallization yields an additional crude ester which is passed to the saponification step.

Example 36

3- (p-chlorophenyl) pyrrole

22.0 g of crude ethyl 4- (p-chlorophenyl) pyrrole-3-carboxylate (a mixture of the recrystallized product of the previous example and the product obtained from the mother liquor obtained by recrystallization) in 150 ml of 10% aqueous sodium hydroxide solution for 2.5 hours. stirring under reflux. The mixture was cooled, extracted with food and acidified. After filtration and drying, 11.6 g of a precipitate are obtained.

10.5 g of the acid are refluxed in 100 ml of beta-ethanolamine for 3 hours. After cooling, the mixture was poured onto 400 ml of ice and the resulting mixture was extracted four times with chloroform. Chlorophoma ol15

The product was dried over magnesium sulfate, treated with activated charcoal and concentrated in vacuo. The resulting brown solid was chromatographed on silica gel with ethyl acetate / hexane 1: 1. 4.0 g of a white solid are obtained. Melting point 117-118 ° C. 5

Example 37

To a mixture of 3- (p-chlorophenyl) pyrrole-2-carboxaldehyde in 0.86 g (12 mmol) of dimethylformamide in 10 mL of ethylene dichloride was added 1.49 g (12 mmol) under nitrogen atmosphere and cooling in an ice bath for 25 minutes. a mixture of oxalyl chloride in 10 ml of dichloromethane was added. The ice bath was removed, the mixture was stirred for an additional 15 minutes and then cooled again in an ice bath. A mixture of 1.5 g (8.5 mmol) of 3- (p-chlorophenyl) pyrrole in 25 ml of ethylene chloride is then added over 20 minutes.

The ice bath was removed and stirred for an additional 30 minutes, then poured into 50 ml of ice water and poured into 6 ml of 50% sodium hydroxide solution. The resulting mixture was extracted with ether and chloroform, and the combined organic phases were dried over magnesium sulfate and concentrated in vacuo. The resulting solid was chromatographed on silica gel with ethyl acetate / hexane 1: 1. 0.63 g of a white solid is obtained which can be directly used for the preparation of 3- (p-chlorophenyl) pyrrole-2-carbonitrile.

Example 38

3- (p-Chlorophenyl) pyrrole-2-carbomtril 30

A solution of 3- (p-chlorophenyl) pyrrole-2-carboxaldehyde (0.63 g, 3.1 mmol) in water (10 mL) was stirred and cooled with ice while slowly adding 0.52 g (4.6 mmol) of hydroxylamine-O. of sulfonic acid in 10 ml of water. After the addition was complete, the cooling bath was removed and the mixture was heated for 25 minutes. Upon cooling, a solid precipitates which is collected. NMR test product is a mixture of starting aldehyde. The mixture was reacted with 0.49 g (4.2 mmol) of hydroxylamine 40 O-sulfonic acid in a total of 30 ml of water as described above. The reaction mixture was heated at 60-70 ° C for 2 hours, cooled, and the solid filtered, chromatographed on silica gel with ethyl acetate / hexane 1: 1. 0.40 g of a pink solid is obtained. Melting point 114-45-115 ° C.

Example 39

4f-Dibromo-3- (p-chlorophenyl) pyrrole-2-carbonitrile 50

To a mixture of 3- (p-chlorophenyl) pyrrole-2-carbonitrile (0.40 g, 2.0 mmol) in chloroform (25 mL) was added bromine (0.63 g, 4.0 mmol). After 20 minutes, the precipitate was filtered off and recrystallized from ethyl acetate. 0.21 g of pink crystals are obtained, m.p. 250 ° C. 55

Elemental analysis based on the formula ^, Η ₅ ΒΓ ₂ αΝ:

calculated C 36.62% HI, 39% Br 44.38% Cl, 9.85% N, 7.77% found: C, 36.92% H 1.32% Br 44.62% Cl, 9.88% N7,50%. 60

Example 40

Ethyl 5-bromo-4- (p-chlorophenyl) pyrrole-3-carboxylate

To a solution of 1.6 g (0.0067 mmol) of ethyl 4- (p-chlorophenyl) pyrrole-3-carboxylate in 40 ml of tetrahydrofuran was added in portions at 25-28 ° C 1.14 g (0.0064 mmol) of N-bromo. succinimide is added. After the addition was complete, the reaction mixture was stirred overnight at room temperature, then concentrated in vacuo and the solid residue partitioned between water / ether. The ether layer was separated, dried over magnesium sulfate and worked up. 1.9 g (90%) of a white solid are obtained which is purified by stirring in 80:20 hexane / ethyl acetate. The insoluble solid (1.3 g, 62%) was filtered off, m.p. 161-164 ° C.

Analysis for C ₁₃ H _1I basis BrClNO ₂ Calc'd:

Calculated: C 47.50% H3.34% N4.26%

Br 24.33% Cl 10.80% Found C 47.39% H3.38% N4.12%

Br 24.29% Cl 10.77%.

Example 41

5-Bromo-4- (p-chlorophenyl) pyrrole-3-carboxylic acid 15 g (0.045 mmol) of ethyl 5-bromo-4- (p-chlorophenyl) -pyrrole-3-carboxylate in 200 ml of 10 wt. sodium hydroxide solution and the suspension is refluxed. After complete dissolution, reflux for an additional 40 minutes. The mixture is cooled, filtered and the filtrate is acidified. The white precipitate (8.0 g, 58%) was filtered and dried. Melting point above 205 ° C. NMR (dg-DMSO) showed 7.52 (d) pyrrole proton, monobrominated by mass spectrum.

Example 42

2-Bromo-3- (p-chlorophenyl) pyrrole 8.0 g (0.026 mmol) of 5-bromo-4- (p-chlorophenyl) pyrrole-3-carboxylic acid are added to 24 ml of aminoethanol and the suspension is slowly added. It is heated to 110-120 ° C and maintained at this temperature for one hour. The solution was cooled and poured into water. Extract with ether and assay the extract by thin layer chromatography (hexane / ethyl acetate 75:25): Mostly fast moving spot and few slow moving components. Workup of the ethereal phases (4.0 g, 56%) gave a dark solid which was 2-bromo-3- (p-chlorophenyl) pyrrole and directly applicable 5-bromo-4- (pchlorophenyl) pyrrole. For the preparation of -2-carbonitrile.

Example 43

5-Bromo-4- (p-chlorophenyl) pyrrole-2-carbonitrile 4.0 g (0.015 mmol) of freshly prepared 2-bromo-3- (chlorophenyl) -polyTo] in 25 ml of dry dimethoxyethane dissolved. Chlorosulfonyl isocyanate (3.08 g, 0.022 mmol) was added at a temperature below 25 ° C. The reaction mixture was stirred overnight, then dimethylformamide (6 mL) was added and the mixture was stirred for an additional three hours. Finally, the solution was poured into water and

Filter the precipitate. This gave 3.8 g (90%) of a brown solid. Dry column chromatography (hexane / ethyl acetate 80:20) gave 1.4 g (33%) of a white solid. Mp 202-204 ° C.

Analysis for CNH ₆ BrCl _2: Calcd: C, 46.90% H2,13% N9,95%

Cl 12.61% Br 28.39% Found: C 47.20% H2.09% N9.80%

Cl 12.36% Br 27.42%.

Example 44

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

2.2 g (0.078 mol) of 5-bromo-4- (p-chlorophenyl) pyrrole-2-carbonitrile are dissolved in 30 ml of dry dioxane. The solution

Heat with 1.3 g (0.008 mol) of bromine in 20 ml of dioxane and stir overnight at room temperature. The reaction mixture was poured into water to give 2.6 g (92%) of a solid. A 1.6 g portion was purified by flash chromatography on hexane / ethyl acetate 75:25 to give 0.8 g of a gray solid. Melting point 191-194 ° C.

Elemental analysis: Calculated for C 11 H ₅ Br ₂ ClN ₂ : C, 36.61; H, 1.38; N, 7.76.

Cl 9.84% Br44.3% Found: C 37.46% H 1.25% N7.41%

Cl 9.53% Br 42.99%.

Example 45

3- (3,4-Dichlorophenyl) -4-nitropyrrole

A solution of 2.66 g (66 mmol) of a 60% w / w oily sodium hydride slurry in dry ether was taken up in 150 ml of dry ether. To the suspension, 12.0 g (5.5 mmol) of 3,4-dichloro-beta-nitrostyrene and 10.8 g (5.5 mmol) of (p-tolylsulfonyl) methyl isocyanide in 50 mL of dimethyl are added over 15 minutes. sulfuric acid in 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, dried over magnesium sulfate and evaporated. The crude product (10.6 g) was purified by chromatography on silica gel with chloroform / ethyl acetate (4: 1). The solid fraction (7.2 g) was recrystallized from chloroform / ethyl acetate / hexane to give 3.0 g of a yellow solid. 187-188 ° C (dec.).

Elemental analysis: Calculated for C 46. H ₆ Cl ₂ N ₂ O ₂ : C 46.72% H 2.35% N 10.90% Found: C 46.96% H 2.60% N 9.77.

Example 46

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

2.5 g (97 mmol) of 3- (3,4-dichlorophenyl) -4-nitropyrrole

To a mixture of 200 ml of chloroform was added sulfuryl chloride (2.95 g, 22 mmol) at 40 ° C over 1 minute. 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 resulting brown solid was chromatographed on silica gel with chloroform / ethyl acetate 4: 1. The orange solid fraction was recrystallized from chloroform and chromatographed again on silica gel with chloroform / ethyl acetate 4: 1. 0.36 g of a yellow solid are obtained. Melting point 193-194 ° C.

Prepared in the same manner as in Examples 45 and 46

2,5-dichloro-3-nitro-4-phenylpyrrole. Melting point 193-194 ° C (dec.).

Example 47

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

2-Chlorophenyl-3-cyanopinol (3.0 g, 0.015 mol) prepared in Example 4 was dissolved in dry dimethoxyethane (50 ml) and chlorosulfonyl isocyanate (3.39 g, 0.024 mol) was added. Batching is exothermic, so slight cooling is required. The reaction mixture was stirred at room temperature for 3 hours, then 6-7 ml of dimethylformamide was added and stirred for an additional 4 hours. It was then poured onto ice and the white solid (3.4 g, 100%) filtered. A 1.0 g portion was purified by dissolving in ethyl acetate and filtering the solution through a 60 mL silica gel filter column. The filtrate was evaporated to give 0.7 g of a solid. Melting point 235-240 ° C.

The following compounds of formula XV can be prepared as described in Example 47:

R L OP. (° C) 3-Cl 4-C1 • Above 225 H 4-OCF ₃ 185-190 H 4-CF ₃ 180-185

Example 48

3-Bromo-5- (p-chlorophenyl) pyrrole-2,4dikarbonitril

5- (p-Chlorophenyl) pyrrole-2,4-dicarbonitrile (1.0 g, 0.004 mol) was dissolved in dioxane (20 mL) and a solution of bromine (0.8 g, 0.005 mol) in dioxane (10 mL) was added. The reaction mixture was stirred at room temperature for several hours and then poured into water. The white solid (1.2 g, 100%, m.p. 225 ° C) was identical to the structure shown by mass spectrometry.

The following compounds of formula XVI can be prepared as described in Example 40:

R L Op. ( ^E C) 3-Cl 4-C1 Over 250 H 4-OCF3 218-223 H 4-CFj 239-241

HU 204971 Β

Example 49

Bromo-fumaromtril

Under nitrogen, 15.6 g (0.2 mol) of fumaronitrile in 150 ml of chloroform are refluxed until a clear solution is obtained. A solution of bromine (5.3 ml, 0.2 mol) in chloroform (25 ml) was added dropwise over 30 minutes, causing the reaction mixture to slowly decolorize and acidify. The mixture is refluxed for a further 90 minutes while the solution is discolored. The reaction mixture was cooled and the solvent removed under reduced pressure. The weight of the oil obtained is almost theoretical for bromofumaronitrile. The oil was distilled at a temperature below 120 ° C at 0.2 mm Hg (rapid decomposition at higher temperature). The resulting semi-solid slowly waxes. M.p. -4347 ° C.

Elemental Analysis for C ₄ HBrN: Calculated: C 30.57% H0.64% N 17.83% Found C 29.13% H0.75% N 16.94%.

Example 50

2-phenyl-pyrrole-3,4-dicarbonitrile

Under a nitrogen atmosphere, a solution of 4.7 g (0.03 mol) of bromofumaronitrile and 7.1 g (0.03 mol) of N- (trimethylsilyl) methyl-S-methylbenzene thioimidate in 35 ml of hexamethylphosphoramide was added. and stirred at room temperature. Water (1.6 mL, 0.09 mol) washed with hexamethylphosphoramide (10 mL) was added in one portion. Almost immediately, an exothermic reaction begins and the temperature rapidly rises to 100 ° C. The resulting dark red solution was stirred at ambient temperature for 20 hours and then poured into ice water. The resulting gummy material slowly converts to a beige solid. This material was filtered, washed with cold water and dried on the filter. It was further dried under vacuum at 60 ° C and recrystallized twice from C ₂ H ₄ Cl ₂ . This gave a white powder, mp 197-200 ° C.

Analysis for C ₇ H _{I 2} N _3: Calcd C, 74.61% H3,63% N 21.76% Found C 74.45% H3,84% N 21.61%

Example 51

2-Bromo-5-phenylpyrrole-3,4-dicarbonitrile Under nitrogen, 1.4 g (0.0075 mol) of 2-phenyl-pino-3,4-dicarbonitrile were added to 35 ml of chloroform, the bulk of the solid dissolved. A solution of bromine (0.4 mL, 0.008 mol) in chloroform (5 mL) was added dropwise over 20 minutes. The color of the reaction mixture changes rapidly at first and a new gummy solid precipitates and then remains the same. The mixture was stirred at room temperature for 30 minutes and then refluxed to give a solid. After refluxing for 90 minutes, the reaction mixture was cooled and a small portion examined by HPLC analysis. Studies show that about 60% of the starting material remains. Fresh bromine (0.2 mL, 0.004 mol) was added in one portion and refluxed for an additional 45 minutes. A small detail test shows that 10% of the starting material remains. Further

Bromine (0.2 mL, 0.004 mol) was added to the reaction mixture and the suspension was refluxed for 30 minutes. It is then cooled and stirred for 18 minutes at room temperature. The solvent was removed under reduced pressure. The greenish solid was extracted with hot chloroform to give a dark residue. The extract was recrystallized twice from C ₂ H ₄ Cl ₂ and filtered hot. The light yellow filtrate rapidly precipitates a white precipitate. Cool to -10 ° C and filter the white solid. Melting point5 225-258 ° C.

Analysis for C _I2 H ₆ BrN _3: Calcd: C 52.94% H 2.21% N 15.44% Br 29.41% found C 51.64% H 2.35% N 14.91% Br 28.69%.

Example 52

2- (3,4-Dichlorophenyl) -5-nitropyrrole-3-carbonitrile 3.0 g (0.013 mol) of 2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile in 50 ml of acetic anhydride and 0 6 ml of a 90% mixture of nitric acid are added, whereby a slightly exothermic reaction is initiated. The reaction mixture is slowly warmed to 30 ° C and is kept at 30-33 ° C until complete dissolution. Gradually a new solid precipitates. The reaction mixture was stirred at room temperature for 2-3 hours and then poured into water / ice to decompose acetic anhydride.

After stirring for 1 hour, the mixture was filtered and the resulting solid (2.9 g, 82%) was dried. A 1.5 g portion was purified by column chromatography on silica gel with 75:25 hexane / ethyl acetate to give 0.7 g of a yellow solid. Mp 228-231 ° C.

Analysis for C _H C1 ₂ H ₅ N ₃ O ₂ requires: C 46.80% H 1.77% N 14.89% Cl 25.17% Found: C 46.50% N 1.96% N 14 , 27% Cl 24.30%.

Starting from 2- (p-chlorophenyl) pyrrole-3-carbonitrile as described above, 2- (p-chlorophenyl) -5-nitropyrrole-3-carbonitrile is obtained, m.p. 201-206 ° C.

Starting from 2- (p-trifluoromethylphenyl) pyrrole-3-carbonitrile, 2- (p-trifluoromethylphenyl) -5-nitropyrrole-3-carbonitrile, m.p. 164-165.5 ° C. .

Example 53

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

2- (3,4-Dichlorophenyl) -5-nitropyrrole-3-carbonitrile (0.5 g, 0.0017 mol) was dissolved in dry dioxane (10 ml) and bromine (0.28 g, 0.0017 mol) was added. a solution of dioxane is added. The reaction mixture was stirred overnight and then poured into water. The solid (0.54 g, 88%) was recrystallized from 5 ml of acetonitrile to give 0.26 g of product, m.p. 195-200 ° C.

Elemental analysis based on C _n H ₄ BrCl ₂ N ₃ O ₂ :

EN 204971 Β Calculated: C 36.57% H 1.10% N 11.63%

Br 22.13% Cl 19.67% Found: C 36.46% H 1.29% N 11.50%

Br 21.63% Cl 19.28%.

In the same manner as in Example 53, starting from 2- (p-chlorophenyl) -5-nitrimadole-3-carbonitrile, 4-bromo-2- (p-chlorophenyl) -5-nitropyrrole-3-carbonitrile is obtained, m.p. 180-185 ° C.

Example 54

5- (3,4-Dichloro-phenyl) -4-mtropirrol-2-karbomtril

To a suspension of 5- (3,4-dichlorophenyl) pyrrole-2-carbonitrile (1.2 g, 5.1 mmol) in acetic anhydride (25 mL) at -30 ° C under nitrogen atmosphere (0.3 mL) was added (5.1 mmol). 90% by weight of nitric acid was added dropwise. Upon exothermic reaction, the temperature rises to 45 ° C and the solution dissolves. The mixture was stirred for 2 hours, then poured into water (50 mL) and stirred vigorously for 5 minutes. The beige precipitate was filtered and dissolved in a small amount of acetone. Chromatography on silica gel with hexane / ethyl acetate (3: 1) afforded 1.2 g (84%) of the nitrimadole as a white solid, m.p.

Example 55

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

To a suspension of 0.6 g (2.1 mmol) of 5- (3,4-dichlorophenyl) -4-nitropyrrole-2-carbonitrile in 10 mL of dioxane at 25 ° C under nitrogen atmosphere was added 0.3 g (2.1 mmol) of bromine. of a solution of dioxane in dioxane was added dropwise. The reaction mixture was stirred overnight and water (50 mL) was added. The yellow solid precipitate was filtered and dried under vacuum at 50 mm Hg at 45 ° C. 0.7 g (90%) of brominated pyrrole is obtained in the form of a pale yellow solid, m.p. 200 ° C.

Example 56

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

Trifluoroacetic anhydride (1.7 ml, 0.012 mole) was added in one portion to powdered 2- (p-chlorophenyl) glycine (11.4 g, 0.06 mole), resulting in an exotherm at about 40 ° C. a yellow color appears on the surface of the solid. The reaction mixture is slowly heated to 70 ° C whereby the major part of the solid is dissolved in an orange oil. After about 2 hours, the solids are completely soluble and then heated for an additional 1 hour. The solvent was removed in a vacuum rotary evaporator. The odor of trifluoroacetic acid persists even after double dosing of toluene and removal under reduced pressure. The resulting yellow semi-solid (theoretical, purity above 90% by HPLC), which corresponds to the title compound, is used directly for the next step without further purification.

Example 57

2- (p-Chlorophenyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile

4- (p-Chlorophenyl) -2-trifluoromethyl-2-oxazolin-5-one (2.5 g, 0.01 mol) was dissolved in 50 ml of nitromethane. 2-Chloroacrylonitrile (8.0 mL, 0.10 mol) was added in one portion and the reaction mixture was refluxed for 18 hours under nitrogen. The reddish-brown solution was poured into -5 ° C in an ice / acetone bath and the precipitate was filtered off, washed with a little cold nitromethane. The solid was recrystallized from hot ethylene chloride to give 1.8 g (56%) of white crystals, m.p. 238-241 ° C (dec.).

In the procedure of Example 55, using the appropriate arylglycine and following the procedure described above, the compounds of formula (XVII) can be prepared.

R L Mp. ( "C) H H 215-218 H 4-CH ₃ 191-193 H 4-OCH ₃ 168-180 (decomposes) 3-C1 4-C1 245-246 (decomposes) H 4-CF ₃ 218-219

Example 58

4-Bromo-2- (p-chlorophenyl) -5- (trifluoromethyl) pyrrole-3karbonltril

Under nitrogen, a suspension of 1.6 g (0.005 mol) of 2- (chlorophenyl) -5-trifluoromethylpyrrole-3-carbonitrile in 25 ml of acetic acid is heated to about 60 ° C until a clear solution is obtained. A solution of bromine (0.8 ml, 0.015 mol) in acetic acid (10 ml) was added dropwise to the solution under reflux for 15 minutes. The reaction mixture was refluxed for 6 hours and then stirred at room temperature for 18 hours. About 80% conversion was detected in the reaction mixture by HPLC. The mixture is refluxed and a further 0.5 ml (0.01 mol) of bromine in 5 ml of acetic acid is added dropwise. Reflux for about 3 hours after showing a conversion above 95%. The reaction mixture was cooled and the solvent removed in a rotary evaporator. The resulting dark gray solid was mixed with toluene and the solvent removed under reduced pressure to leave an acetic acid odor. The residue was dissolved in hot toluene (75 mL) and the cloudy solution was recrystallized twice from C ₂ H ₄ Cl ₂ . The light pink solution becomes a white solid upon cooling. The solution was cooled in a refrigerator and the precipitate was filtered, washed with hexane and dried on the filter. Further drying under vacuum at 45 ° C gave 1.2 g (about 60%) of product, mp 247-250 ° C (dec.).

Analysis for C _I2 H ₅ BrClF ₃ N ₂ Calc'd:

Calculated for C 41.20% H 1.43% N8.01%

Br 22.89% Cl 10.16% F 16.31% Found C41.27% HI, 48% N8.10%

Br 22.92% Cl 10.16% F16.03%.

Bromination of the corresponding 2-aryl-5- (trifluoromethyl) pyrrole-3-carbonitrile gave the following compounds of formula XV111 as described in Example 57.

R L Mp (° C) H H 235-238 H 4-CH ₃ 244-245 3-C1 4-Cl 218-223 H 4-CF ₃ 225-226

Example 59

2- (4-Chloro-phenyl) -5-trifluoromethyl-pyrrole-3,4dikarbonitril

Trifluoroacetic anhydride (3.1 ml, 0.022 mol) was added in 20 portions to (4-chlorophenyl) glycine (2.0 g, 0.011 mol), resulting in an immediate yellow color and slight reflux. The mixture is slowly heated to reflux to give a yellow / orange solution which is spun for an additional two hours. The reaction mixture was cooled and the solvent removed under reduced pressure. Double addition of toluene and removal under reduced pressure gave a thick oil (V _c0 - 1800 cm ^-1 ). The residue was dissolved in a small amount of insoluble material in 40 ml of CH ₃ NO ₂ and 30 ml

Bromo-fumaronitrile (2.7 g, 0.018 mol) was added in one portion. The resulting solution was refluxed for 18 hours, then the solvent was removed from the dark red solution under reduced pressure and the residue was dissolved in CH ₂ Cl ₂ . Few insoluble materials are filtered off. The material was fractionated by dry column chromatography (silica gel, 3% w / w 2-PrOH in CH ₂ Cl ₂ ) and the appropriate fractions were collected. Concentration of a fraction gave the title compound as a yellow solid, which was recrystallized from CH ₃ CN to give 0.2 g of a yellow solid, m.p. 238-241 ° C (some decomposition).

Example 60 45 p-Chloro-O - [(formylmethyl) amino] cinnamoyl diethyl acetal

A solution of p-chlorobenzoylacetonitrile (250.0 g, 1.39 mol) in 2,2-diethoxyethylamine (203 ml, 185.9 g, 1.39 mol) and dry toluene (1300 ml) was stirred with stirring for 20 hours. The resulting water (23.8 mL, 95.2% of theory) was collected on a Dean-Stark flask. After filtration, the solution was filtered through a column of silica gel (7 cm x 7 cm.). The filtrate was concentrated in vacuo.

354.3 g (86.4% crude yield) of pure dark oil are obtained which slowly solidifies. The solid was recrystallized from hot cyclohexane to give 324.2 g (79.1%) of a 60 waxy orange solid. The product was found to contain 70% Z and 23% E of p-chloro-3 - [(forynylmethyl) amino] cinnamonitrile diethyl acetal by NMR, m.p. 60-72 ° C.

The following analytical data are taken from another sample, prepared in the same way:

IR (nujol): 3325 (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 = 7.47 (d, J = 8.6 Hz, 2.12 H, 2 aromatic H), 7.37 (d, J = 8.6 Hz, 7.12 H, 2 aromatic H),

5.10 (E), 4.86 (Z) (broad, t, 1.25 H, one NH), 4.69 (Z), 4.60 (E) (t, J = 5.1 Hz, 1.05 H, one methine H on the acetal carbon), 4.07 (E) and 4.05 (Z) (s, 0.83 H, enamine beta H), 3.71 (E) and 3.68 ( Z) (q, J = 7.1 Hz, 2.22 H, 2 methylene H on one of the two ethoxy groups), 3.56 (Z) and 3.53 (E) (q, J = 7, I Hz, 2, 22 H, two methylene H on one of the two ethoxy groups), 3.18 (t, J = 5.1 Hz, 1.77 H, two methylene H on the ethylene acetal group), 1.20 (t, J = 7, 1 Hz, 4.90 H, 6 methyl H on the two ethoxy groups).

C-NMR (chloroform): δ - 161.21 (alpha-enamine),

136.29 (Z) and 134.60 (E) (C-1 or C-4 phenyl C),

134.08 (Z) and 132.30 (E) (C-1 or C-4 phenyl C),

129.34 (Z) and 129.89 (E) (C-2.6 or C-3.5 phenyl)

C), 128.94 (Z) and 128.63 (E) (C-2.6 or C-3.5 phenyl C), 121.19 (Z) and 119.50 (E) (nitrile), 99 , 43 (Z) and 100.63 (E) (beta-enamine), 61.88 (Z) and 63.25 (E) (methine on the acetal group), 62.64 (Z) and 63.03 (E) (methylene on ethoxy), 46.32 (Z) and 47.33 (E) (methylene on ethylamine), 15.26 (methyl on ethoxy).

Elemental Analysis (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. %.

As described above, but employing, instead of p-chlorobenzoylacetonitrile, the corresponding benzoylacetoylacetonitrile and / or 2,2-diethoxyethylamine, the corresponding and in the acoxy moiety, C2-C4 dialkoxyethylamine the following compound of formula (XIX) may be prepared:

L M R _(Cl-C4 alkoxy) ₂ H H p-CH ₃ OCO (OC ₂ H ₅ ) ₂ 68-73 H p-CH ₃ H (OC ₂ H ₅ ) ₂ 59-69 H m-OCH ₃ p-OCH ₃ (OC ₂ H ₅ ) ₂ reddish orange semisolid H -CH = CH-CH = CH- (OC ₂ Hj) ₂ 62-70 p-Cl H H (OCH ₃ ) ₂ - H p-CH ₃ H (OCH ₃ ) ₂ - H m-Cl p-Cl (OC ₂ H ₅ ) ₂ - H H p-COCF ₃ (OC ₂ Hj) ₂ - H H p-cf ₃ (OC ₂ H ₅ ) ₂ -

HU 204,971 Β

Example 61

2-p-chlorophenyl) pyrrole-3-carbonitrile

To 108 ml of trifluoroacetic acid was added 54.00 g (0.183 mol) of solid p-chloro-β- ((formylmethyl) amino) cinnamonitrile diethyl acetal under stirring at 23 ° C over 45 minutes. The addition causes an exotherm at 30 ° C and after 32 minutes a solid precipitate forms. After stirring for 30 minutes at room temperature, the reaction mixture was filtered under vacuum and the solid washed first with trifluoroacetic acid, second with ethyl acetate / hexane and finally with hexane. 16.83 g (45.4%) of a white solid are obtained, m.p. 165-166 ° C.

The following analytical data were taken from another sample prepared in the same way.

IR (nujol): 3275 (br, s), 2225 (s), 1502 (s), 1410 (m),

1275 (m), 1200 (m), 1108 (s), 1023 (m), 999 (m),

908 (m), 843 (s), 752 (s), 722 (s), 695 (s), 620 (s) cm -1. 1 H-NMR (acetone): δ = 11.22 (v, broad s, 0.99 Η, 1 red H), 7.82 (d, J = 8.9 Hz, 2.46 H, 2 aromatic phenyl)

H), 7.51 (d, J-B, 9 Hz, 2.46 Hz, 2 aromatic phenyl H),

7.02 (t, J = 2.6 Hz, 1.01 H, one red H at C-5),

6.58 (t, J-2.6 Hz, 0.77 Η, 1 red at H C-4). C-NMR (acetone): δ - 137.73 (pyrrole C-2), 134.42 (p-chlorophenyl at C-4), 129.93 (methine phenyl at C-3.5), 128, 07 (methine phenyl at C-2.6), 121.21 (pyrrole at C-5), 117.93 (nitrile), 113.78 (pyrrole at C-4), 90.86 (pyrrole at C) at -3).

Elemental Analysis (MW 202.64): Calculated: C 65.19% H 3.48% N13.83% C117.50% Found: C 64.18% H 3.52% N 13.63% Cl 17.74%. .

By the procedure described above, but in some cases using concentrated hydrochloric acid instead of trifluoroacetic acid, the following compounds of formula (XX) can be prepared:

M and / or R Mp (° C) Applied acid 4-Cl 165-166 cc.HCl, CF3OOH 3,4-Cl 216-221 CF3COOH 2-C1 156-157 CF3COOH 4-OCF ₃ 143-145 CF3COOH 4-CF3 179-180 CF3COOH 2,4-Cl 197-199 CF3COOH 3-Cl 150-156 CF3COOH 4-CN 210-212 CF3COOH 4-F 167-170 cc.HCl 4-SO ₂ CH ₃ 221 to 221.5 CF3COOH 3,4-di-F 173 to 175.5 CF3COOH 3-CF3 166-168 CF3COOH 4-COOCH3 155.5 to 158 CF3COOH 4-CH3 117-137 CF3COOH 4-NO2 174-177 CF3COOH

Example 62

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

To a solution of 16.83 g (83.1 mmol) of 2- (p-chlorophenyl) pyrrole-3-carbonitrile in 450 ml of glacial acetic acid at 36 ° C with stirring for 18 minutes, 14.7 ml (24.70 g, 183 g) (0 mmol) of sulfuryl chloride was added dropwise. After the addition, a slightly exothermic reaction occurred at 39 ° C and after 16 minutes the reaction mixture was filtered under vacuum. The solid was washed first with acetic acid and then with water. Recrystallization from hot ethyl acetate gave a solid, m.p. 259-261 ° C.

The following analytical data were taken from another sample prepared in the same way:

IR (nujol): 3170 (bs), 3100 (m), 2225 (s), 1508 (m), 1097 (m), 825 (s), 717 (m), 660 (m) cm ^-1 . 1 H-NMR (DMSO): δ = 7.72 (d, J = 8.6 Hz, 2.00H, 2 aromatic H), 7.56 (d, J = 8.6 Hz, 2.00H, 2 aromatic H). C-NMR (DMSO): δ = 136.01 (pyrrole at C-2), 133.92 (p-chlorophenyl at C-3.5), 129.09 (p-chlorophenyl at C-3.5) .

127.41 (p-chlorophenyl at C-4), 127.11 (p-chlorophenyl at C-4)

At C-1), 114.49 (nitrile), 114.10 (pyrrole at C-5),

110.92 (pyrrole at C-4), 90.09 (pyrrole at C-3).

H, 1.86; N, 10.32; Cl, 39.17; Found: C, 49.22; H, 2.12; N, 9.85; Cl, 39. 03%.

Example 63

4.5-Dibromo-2- (a, a, v-trifluoro-p-tolyl) pyrrole-3-carbonitrile

To a solution of 0.8 g of 2- (a, a, a-trifluoro-p-tolyl) pyrrole-3-carbonitrile in 70 ml of chloroform was added 2 ml of bromine with stirring. The reaction mixture was stirred overnight and the precipitated white solid was filtered. TLC (ethyl acetate / hexane 1: 1) shows the product to be a single spot, m.p. 230 ° C.

Analysis calculated for C C HHjBB ^F: C: C, 36.55% Η 1.27% N7, II% Br 40.61% Found: C 36.40% Η 1.08% N 6.99% Br 40.55%.

In the same manner as above, but substituting 2- (α, α, α-trifluoro- p-tolyl) pyrrole-3-carbonitrile, the appropriately substituted phenylpyrrole-3-carbonitrile can be used to prepare the following compounds of formula XXI:

L M R X Y Mp (° C) H H 4-NO ₂ Br Br 274-277 H H 4-F cl cl Above 220 H H 4-F Br Br Above 220 H H 4-SO ₂ CH ₃ cl cl Over 230 H 3-F 4-F cl cl Over 230 H 3-F 4-F Br Br Above 220 2-Cl 3-Cl 4-Cl cl cl 2-Br 3-Br 4-Br Br Br H H 4-OCF3 cl cl 222-225

HU 204971 Β

L M R X 1 ^Y Op. ('C) H H 4-OCF ₃ Br Br H H 4-OCF ₃ cl H H H 4-CN Br Br Over 230 H H 4-CN cl cl Above 240 H H 4-SO2CH3 Br Br Over 230 H H 4-NO2 cl cl 246-249 H 3-C1 4-Cl Br Br Above 260 H H 3-CF ₃ cl cl Over 230 H H 4-COCH ₃ 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-Cl Br Br Over 230 H H 3-Cl cl cl Over 230 H 2-C1 4-Cl cl cl Over 230 H H 4-Cl Br Br 273-274 H H 2-C1 Br Br Over 230 H H 4-CF ₃ cl cl Over 230 H H 4-Br cl cl Above 235 H H 2-C1 cl cl Over 230 H 3-C1 4-Cl cl cl Above 235 H H H cl cl 254-255

L M R (C 1 -C 4 alkoxy) ₂ H p-CH ₃ H (OC ₂ H ₅ ) 2 H m-OCH ₃ p-OCH ₃ (OC ₂ H ₅ ) ₂ H -CH-CH-CH-CH- (OC ₂ H ₅ ) ₂ p-Cl H H (OCH ₃ ) ₂ H p-CH ₃ H (OCH ₃ ) 2 H H p-CF ₃ (OC ₂ H ₅ ) ₂

Example 65

23-Dichloro-4-nitro-5-phenylpyrrole

A mixture of 1.56 g (0.0083 mol) of 3-nitro-2-phenylpyrrole in 60 ml of diol 15 xane was cooled in an ice bath while 25.9 g (0.0182 mol) of sodium hypochlorite was added dropwise. The reaction mixture was stirred for 45 minutes and then acidified with concentrated hydrochloric acid. Dilute with water and ethyl ether. The phases were separated and the upper organic layer was washed with water, dried over anhydrous magnesium sulfate and concentrated in vacuo. 2.21 g of a yellow solid are obtained, which is purified by chromatography on silica gel eluting with increasing amounts of ethyl acetate / hexane. Yield: 0.77 g (36%) of a yellow solid, m.p. 190-190.5 ° C. Elemental analysis based on the formula Ci ₀ H ₆ N ₂ O ₂ C1 ₂ :

Calculated: C 46.72% H2.35% N 10.90% Found C 46.96% H286% N 10.02%.

Example 64 α- (2,2-Dieloxyethylamino) -? - mtrostyrene and 3-nitro-2-phenylpyrrole

5.7 g (0.0345 moles) of (-nitroacetophenone) are taken up in 100 ml of toluene and 4.6 g (0.0345 moles) of aminoacetaldehyde diethyl acetal are added. The mixture is filled into a 250 ml flask, fitted with a Dean-Stark plug, filled with a 4A molecular sieve and refluxed for 18 hours.Toluene was removed in vacuo to give 8.36 ct- (2,2-diethoxyethylamino) -P-nitrostyrene as a brown oil Concentrated hydrochloric acid (50 ml) was added to the oil, and the flask was stirred to give a yellow slurry, and after 10 minutes the solid was filtered to give 2.48 g of a yellow solid, which was recrystallized from ether / ethyl acetate / hexane , yield 2.08 g (31%), m.p. 190-192 ° C.

IR.-MSScm-'íNOj)

1 H-NMR (CDCl 3 - MSO): δ - 6.73 (m, 2H), 7.46 (m,

5H).

As described above, but instead of the α-nitroacetophenone, the corresponding substituted nitroacetophenone and / or amino-aldehyde diethyl acetal can be prepared using the appropriate C 1--Cat-2,2-dialkoxyethylamine as its component. the following β-nitro-styrene compounds of formula XXII:

Example 66

3-Cyano-2- (3,4-Dichloro-Phenyl) -N, N-dimethyl-pyrrol-carboxamide

To a solution of 10.0 g (0.0422 mol) of 2- (3,4-dichlorophenyl) -pinO1-3-carbonitrile in tetrahydrofuran was added 13.2 g (0.1176 mol) of potassium tert-butoxide and the mixture was stirred for 1 hour. and stirred at room temperature. thereafter

Dimethylcarbamyl chloride (13.2 mL, 15.31 mol) was added and stirred at room temperature for 16 hours. Additional potassium tert-butoxide (4.4 g, 0.0392 mol) and dimethylcarbamyl chloride (4.4 ml, 5.104 mol) were added, refluxed for 1 hour, cooled to room temperature, and ethyl acetate / water. mix.

The phases were separated, the organic phase was washed with water, dried over anhydrous magnesium sulfate and concentrated in vacuo. The oily residue was purified by flash chromatography on silica gel eluting with 50:50 diethyl ether / hexane. This gave 4.7 g (36%) of the title compound as a white solid, mp 120-122 ° C.

Example 67

N, N-Dimethyl-2B-dibromo-4-cyano-5- (3,4-dichlorophenyl) pyrrole-l-carboxamide

To a solution of 1.0 g of N, N-dimethyl-3-cyano-2- (3,4-dichlorophenethyl) pyrrole-1-carboxamide in tetrahydrofuran

3.8 g of bromine are added, the mixture is stirred for 5 days and then concentrated in vacuo. The brown oily residue was purified by chromatography on silica gel, eluting with a 1: 1 mixture of ether and hexane, and the semi-solid was clay plate22.

HU 204 971 Β zen pressed. 0.45 g of the title compound is obtained in the form of a white solid, m.p. 144-149 ° C.

Example 68

4-Bromo-1-bromomethyl-2- (p-chlorophenyl) -5- (trifluoromethyl) -pyrrole-3-carbonitrile (0.0825 mol) 4-bromo-2- (p-chlorophenyl) ) To a solution of -1-methyl-5-trifluoromethyl-pyrrole-3-carbonitrile in 450 ml of carbon tetrachloride was added 13.2 ml (19.8 g) of bromine and a 77 ml of a 500 ml photochemical reactor under a mercury vapor lamp. Irradiate at 23 ° C for 23 hours. A further 4.4 ml (0.0425 mol) of bromine were then added to the reaction mixture and the irradiation continued for 47 hours. The reaction mixture was washed with aqueous metabisulfite solution, then water, and evaporated to dryness in vacuo. The residue was taken up in 50-60 ml of carbon tetrachloride, mixed with 100 ml of heptane and filtered. 18.3 g of the title compound are obtained in the form of a white solid, m.p. 131-1315 ° C.

Example 69

4-Bromo-2- (p-chlorophenyl) -l- (ethoxymethyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile

To 1000 ml of dry tetrahydrofuran (THF) was added 130.8 g of 4-bromo-2- (p-chlorophenyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile. After stirring, potassium tert-butoxide (43.3 g) was added in portions and the resulting exotherm was controlled on a water bath. Chloromethylethyl ether (36.5 g) was then added in two portions with stirring, and the reaction was followed by thin layer chromatography. After about 4 hours, the reaction mixture was diluted with ether (300 mL), washed with dilute hydrochloric acid and water. The organic layer was separated, dried over magnesium sulfate, filtered and concentrated in vacuo. 122 g of the title compound are obtained, which is recrystallized from 500 ml of isopropyl alcohol. 102 g of the title compound are obtained in the form of a colorless solid, m.p. 99-100 ° C.

Example 70

4,5-Dichloro-2- (3,4-dichloro-phenyl) -l- (l-ethoxyethyl) pyrrole-3-carbonitrile

4.5 g (0.016 mol) of 4,5-dichloro-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile were dissolved in 300 ml of tetrahydrofuran and 2.75 g (0.025 g) in portions under ice-cooling and stirring. moles) of potassium tert-butoxide are added. To the cooled reaction mixture was added a solution of 2.31 g (0.021 mol) of 1-chloroethyl ether in 15 ml of tetrahydrofuran at 10 ° C for 5 minutes. After stirring for half an hour at room temperature, the reaction mixture was concentrated to a volume of 50 ml and poured into a mixture of ethyl acetate (200 ml) and water (100 ml). The organic layer was separated, washed with water (2 x 100 mL), brine (100 mL), dried over anhydrous magnesium sulfate and evaporated. 5.9 g of the title compound are obtained, m.p. 124-126 ° C.

Example 71 p-Chloro-N - [(phenylsulfonyl) methyl] thiobenzamide Sodium benzenesulfinate g (0.1 mol) was dissolved in 100 mL of water and 3.2 g (0.11 mol, 37 wt.) aqueous formaldehyde and a suspension of 17.0 g (0.1 mol) of p-chlorothiobenzamide in 100 ml of 88% by weight formic acid was added. The mixture was stirred at 80-90 ° C for 4.5 hours and then cooled. The solid was isolated by pouring off the liquid, then taken up in ethyl acetate, dried over magnesium sulfate and evaporated in vacuo. 20.7 g (64%) of a yellow solid are obtained. Recrystallization of 17 g of the above solid from methanol gives 6.7 g of a yellow solid which is further suspended in 75:25 hexane / ethyl acetate. Yield: 5.7 g (20.9%), mp 145-150 ° C.

Example 72

M Ethyl p-chloro-N - [(phenylsulfonyl) methyl] thiobenzimidate

A solution of 1.0 g (0.003 mol) of p-chloro-N - [(phenylsulfonyl) methyl] thiobenzamide in methylene chloride was cooled to below 10 ° C, and methyl trifluoride (0.57 g, 0.0035 mol) was added. methane sulfonate was stirred for 3 hours below 10 ° C and for 16 hours at room temperature and then filtered. The filtrate was washed successively with water and dilute potassium carbonate solution, dried over magnesium sulfate and concentrated in vacuo. The oily residue solidifies on standing. This was purified by flash chromatography eluting with methylene chloride followed by 90:10 methylene chloride / ethyl acetate. 0.4 g of the title compound is obtained in the form of a white solid, yield 40%, m.p. 120-123 ° C.

Example 73

To a mixture of 2- (p-chlorophenyl) -4-trifluoromethylpyrrole-3-carbonitrile (ml) dimethoxyethane and 5.5 ml dimethylsulfoxide (0.28 g, 60% w / w sodium hydride) was added. Then, in one portion, a solution of 1.07 g (0.003 mol) of methyl p-chloro-N - [(phenylsulfonyl) methyl] thiobenzimidate and 0.45 g of 85% pure 3,3,3-trifluorocrotonitrile in dimethoxyethane (gas evolution and warming to 30 ° C). After reaching 30 ° C, the reaction mixture was cooled to room temperature, stirred for 90 minutes, poured into water (100 mL) and adjusted to pH 1 with 6N hydrochloric acid. The resulting precipitate was filtered off and dissolved in ether. The ethereal solution was dried over magnesium sulfate and concentrated in vacuo. The resulting brown solid residue was suspended in methylene chloride (10 mL) and filtered. 0.39 g of the title compound is obtained, m.p. 225228 ° C.

Example 74

5-Bromo-2- (p-chlorophenyl) -4- (trifluoromethyl) pyrrole-3 'carbonitrile

0.350 g (0.0013 mol) of 2- (p-chlorophenyl) -4- (trifluoromethyl)

A solution of HU 204971 Β thiylpyrrole-3-carbonitrile in dimethoxyethane was added to a solution of 0.21 g (0.0025 mol) of anhydrous sodium acetate in acetic acid, followed by a solution of 0.26 g (0.0016 mol) of bromine in acetic acid. and stirred overnight at room temperature, then poured into water. The resulting mixture was filtered to give 0.423 g of the title compound as a white solid, m.p. 230 ° C.

Example 75

Ethyl 2- (3,4-dichloro-phenyl) -4,4,4-trifluoroacetoacetate

A suspension of 60% sodium hydride (7.0 g, 0.18 mol) in tetrahydrofuran (200 mL) and diethyl ether (200 mL) was treated with ethyl 4,4,4-trifluoroacetoacetate (26.8 g, 0.146 mol) in tetrahydrofuran (100 mL). solution of 2-bromo-3 ', 4'-dichloroacetophenone (39.1 g) in tetrahydrofuran (200 ml) was added thereto, followed by stirring at room temperature for 45 minutes, cooling to 5-10 ° C. The reaction mixture was allowed to warm to room temperature, refluxed for 5 days, allowed to cool to room temperature and carefully diluted with 200 mL of water. The layers were separated and the organic layer was washed with water (4 x 200 mL), brine (100 mL), dried (MgSO4) and concentrated in vacuo. The resulting viscous oil solidifies on standing. The solid residue was mixed with hexane to give a white solid, m.p. 95-98 ° C, which was used directly in the following procedure.

Example 76

3 ', 4'-Dichloro-4-oxo-5,5,5-trifluoro-valerophenone g (0.054 mol) ethyl 2- (3,4-dichlorophenyl) -4,4,4-trifluoroacetoacetate 300 ml of water, 300 ml of acetic acid and 60 ml of sulfuric acid are heated under reflux for 15 hours. After cooling to room temperature, neutralize by careful addition of solid sodium bicarbonate, filter, dissolve the filtrate in 300 ml of ethyl acetate, dry over sodium sulfate and concentrate in vacuo. The resulting white solid was purified by stirring in cold hexane. 97 g of the title compound are obtained in the form of a white solid.

Example 77

2- (3,4-Dichlorophenyl) -5- (trifluoromethyl) pyrrole

A solution of 3 ', 4'-dichloro-4-oxo-5,5,5-trifluorvalerophenone (10.0 g, 0.033 mol) and ammonium acetate (7.7 g, 0.10 mol) in glacial acetic acid (50 ml) was added under nitrogen for 17 hours. is heated at 55-60 ° C. After cooling, the reaction mixture was poured into 300 mL of ice water, stirred and diluted with 300 mL of dimethyl ether. The phases are separated and the organic phase is washed neutral with saturated sodium bicarbonate solution, then brine, dried over sodium sulfate and concentrated in vacuo. The resulting dark red solution was purified by flash chromatography on silica gel eluting with hexane / ethyl acetate 6: 1. Thus 7.0 g <

Yield (75%) of the title pyrrole as a red oil.

Example 78

2- (3,4-Dichlorophenyl) -3-nitro-5- (trifluoromethyl) pyrrole

A solution of 4.0 g (0.016 mol) of 2- (3,4-dichlorophenyl) -5-trifluoromethylpyrrole in 30 ml of acetic anhydride at 2530 ° C was treated with 0.86 ml (0.018 mol) of 90% (fume) is added dropwise into steam sulfuric acid. After stirring for 30 minutes at 30-40 ° C, the reaction mixture was poured into water (300 ml) and the acetic anhydride was hydrolyzed. The aqueous phase was decanted from the semi-solid product, taken up in ether, dried over magnesium sulfate and concentrated in vacuo. The resulting brown semi-solid residue was taken up in a small volume of hexane and filtered. Purification by chromatography (silica gel / methylene chloride) gave the title compound as a yellow solid, mp 154-156 ° C.

Example 79

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

To a solution of 1.6 g (0.005 mol) of 2- (3,4-dichlorophenyl) -3-nitro-5- (trifluoromethyl) pyrrole in dioxane is added a solution of 0.98 g (0.006 mol) of bromine in dioxane, Stir overnight and evaporate in vacuo. The oily residue was partitioned between ether / water, the ether layer separated, dried over magnesium sulfate and evaporated in vacuo. The resulting oil gradually solidified on standing and the yellow solid was recrystallized from benzene / hexane. This gave the title compound as a dark yellow solid, m.p. 154-156 ° C.

Example 80

2- (p-Chlorophenyl) -3 _! 5bis (-in-methyl) pyrrole

To a solution of 3.0 g of 4-p-chlorophenyl-2- (trifluoromethyl) oxazolin-5-one and 2.0 g of 2-bromo-3,3,3-trifluoropropene in acetonitrile is 1.2 g. triethylamine was added, refluxed for 1 hour, and evaporated in vacuo. The residue was purified on silica gel eluting with 4: 1 hexane / ethyl acetate. 1.6 g of the title compound are obtained in the form of a colorless solid, m.p. 41-43 ° C.

Example 81

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

To a solution of 0.74 g of 2- (p-chlorophenyl) -3,5-bis (trifluoromethyl) pyrrole in acetic anhydride was added dropwise 90% (w / w) nitric acid (0.68 ml), stirred overnight at room temperature for one hour. It is heated at 35-38 ° C and then poured into water. The reaction mixture was extracted with ether. The combined ethereal extracts were dried over magnesium sulfate and concentrated in vacuo. The residue was chromatographed on silica gel with hexane / ethyl acetate 4: 1. 0.27 g of the title compound is obtained in the form of a white solid, m.p. 140-143 ° C.

HU 204,971 Β

Example 82

1- (3,4-Dichlorophenyl) -4,4,4-trifluoro], 3-butanedione

A suspension of 5.0 g (0.125 mol) of 60% w / w mineral oil hydride in tetrahydrofuran was heated to 40 ° C with dropwise addition of 15.0 g (0.079 mol) of 3 ', 4'-dichloroacetophenone and 11.28 A solution of ethyl trifluoroacetate (g, 0.079 mol) in tetrahydrofuran was added, stirred at 40 ° C for 2 hours, treated with isopropanol to decompose excess sodium hydride, evaporated to half its original volume and diluted with water. The mixture was extracted with hexane / ether 1: 1. The combined organic layers were extracted with water. The combined aqueous layers were adjusted to pH 1 with concentrated hydrochloric acid and extracted with ethyl acetate. The organic layer was separated and washed with a saturated sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated in vacuo. 15.3 g of the title compound are obtained in the form of a viscous yellow oil.

Example 83

Ethyl 1-cyano-N- [2- (3,4-dichlorobenzoyl) -trifluoromethyl) vinyl] alginate g (0.078 mol) ethyl 2-cyanoglycinate and 18 g (0.063 mol) 1 A mixture of (3,4-dichlorophenyl) -4,4,4-trifluoro-1,3-butanedione in benzene was refluxed for 4 hours (and the water was removed on a Dean Stark plug). The reaction mixture was evaporated and the brown solid residue was taken up in hexane and filtered. The filtrate was washed with cold ether and air dried. 11.8 g of the title compound are obtained in the form of a colorless solid, m.p. 160-164 ° C.

Example 84

3- (3,4-Dichlorophenyl) -5- (trifluoromethyl) pimyl-2-carbonitrile g (0.005 mol) ethyl 2-cyano-N- [2- (3,4-dichlorobenzoyl) -1 A mixture of (trifluoromethyl) vinyl] glycinate and trifluoroacetic acid (75 ml) was refluxed for 8 hours, then poured onto ice and filtered. The white solid filtrate was dried over silica gel with hexane / ethyl acetate

Chromatograph with 5: 1. The title compound is obtained as a colorless solid, m.p. 215-216 ° C.

Example 85

4-Bromo-3- (3,4-dichlorophenyl) -5- (trifluoromethyl) pyrrole-2-carbonitrile g (0.003 mol) 3- (3,4-dichlorophenyl) -5- (trifluoromethyl) N-Bromosuccinimide (NBS) (0.76 g, 0.004 mol) in pyrrol-2-carbonitrile in tetrahydrofuran was added, stirred for one hour, and then poured into a mixture of water and ethyl acetate. The organic layer was separated, washed with water and brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo. The yellow solid was recrystallized from toluene to give 0.4 g of the title compound as a white solid, m.p. 175-178 ° C.

Example 86

4-Bromo-3- (3,4-dichloro-phenyl) -l- (ethoxymethyl) -5- (trifluoro-methylpyrrole) -2-carbonitrile

A solution of 1.0 g (0.003 mol) of 4-bromo-3- (3,4-dichlorophenyl) -5-trifluoromethyl-pyrrole-2-carbonitrile in tetrahydrofuran was treated dropwise with 0.4 g (0.004 mol) of potassium t butoxide, then 0.4 g (0.004 mole) of chloromethylethyl ether in tetrahydrofuran, stirred overnight at room temperature and then poured into water and ethyl acetate. The phases are separated, the organic phase is washed with water and saturated sodium chloride solution, dried over anhydrous magnesium sulfate and evaporated. The yellow semi-solid was taken up in hexane and filtered. 0.61 g of the title compound is obtained in the form of a white solid, m.p. 98-101 ° C.

Example 87

In the same manner as in Example 9, the appropriately substituted phenylpyrrole-3-carbonitrile or the 2-substituted 3-nitrophenylpyrrole and the corresponding alkylating agent can be prepared by the following compounds:

Preparation of Compounds of Formula II (W = CN)

THE L M R X Y Mp. (° C) CHOCH ₂ H5- 1 ch ₃ H cl 4-Cl cl cl 124-126 CHOCH ₃ 1 ch ₃ H 3-Cl 4-Cl cl cl 135-136 CH ₂ OCH (CH ₃ ) ₂ H 3-Cl 4-Cl cl cl 105-107 CHOCH (CH ₃ ) ₂ 1 CH ₃ H 3-Cl 4-Cl cl cl 86-90

HU 204971 Β

THE L M R X Y Mp. (° C) CHOCH (CH ₃ ) ₂ 1 ch ₃ H H 4-Cl cl cl 93-94 c 1 CH ₂ OCC (CH ₃ ) ₃ H 3-Cl 4-Cl cl cl 143-145 0 II CH ₂ OCCH ₃ H H 4-CF cl cl yellow ch ₃ H 3-Cl 4-Cl Br cf ₃ 154-157 CN H H 4-Cl Br cf ₃ 185-188 CHOC ₂ H ₅ 1 ch ₃ H H 4-Cl Br CF 86-88 CH ₂ OCH ₂ Cff 5 H H 4-Cl Br cf ₃ 86-88 CH ₂ OC ₂ H ₅ H 2-Cl 4-Cl Br cf ₃ 75-80 ch ₂ oc ₂ h ₅ H H 4-F Br cf ₃ 141-143 ch ₂ oc ₂ h ₅ H H 2-F Br cf ₃ 85-86 ch ₂ oc ₂ h ₅ . H H 4-Br Br cf ₃ 85-90 ch ₂ oc ₂ h ₅ H H 3-Cl Br cf ₃ 94-95 ch ₂ oc ₂ h ₅ H 3-F 5-F Br cf ₃ 74-75 ch ₂ oc ₂ h ₅ H H 3-NO ₂ Br cf ₃ 133-134 chooch ₃ 1 ch ₃ H H 4-CL Br CF ₃ 129-131 (Dec) CH ₂ OC ₂ H ₅ H H H Br cf ₃ 155-156 ch ₂ oc ₂ h ₅ H H 4- OCF ₂ CF ₂ H Br cf ₃ 105-107 ch ₂ and ₃ H H 4-Cl Br cf ₃ 105-107 CH ₂ OCH (CH ₃ ) ₂ H H 4-Cl 1 Br cf ₃ 122-123

Preparation of Compounds of Formula II (W-NO ₂ )

THE L M R X Y Op.O CH ₂ OC ₂ H ₅ Η 3-Cl 4-Cl cl cl 118-120 ch ₂ oc ₂ h ₅ H H 4-Cl Br Br 104-105 CHCfiHs H H 4-Cl Br Br 81-82 ch ₃ H H 4-Cl Br Br 197-201 ch ₃ H 3-Cl 4-Cl Br cf ₃ 100-103 choch ₃ 1 ch ₃ H H 4-Br cl cl 97-99 ch ₂ oc ₂ h ₅ H 3-Cl 4-Cl H cf ₃ 70-73

By way of example 88, the corresponding 2-aryl-5- (trifluoromethyl) pyrrole-3-carboxylic compounds (wherein y is trifluoromethylnitrile (Example 57)) can be prepared by bromination of 60 groups described in Example 2):

EN 204971 előállítás Preparation of Compounds of Formula XI (y = CF ₃ )

X L M R Mp. (° C) Br H H 4-C1 247-250 (Dec) Br H 2-C1 4-C1 223-224 Br H H 4-F 141-143 Br H H 3-NO ₂ 250 (Dec) Br H H 3-Cl > 200 Br H 3-F 5-F 250 (Dec) Br H H 2-F 200-201 Br H H 4-Br > 210 Br H H 4-OCF ₂ CHF ₂ 225 (Dec)

Example 89

Using the appropriate arylglycine, the following 2-aryl-5- (trifluoromethyl) pyrrole-3-carbonitrile derivatives of formula (XI) (wherein Y is trifluoromethyl) can be prepared as described in Examples 55 and 57. group):

Preparation of Compounds of Formula XI (y = CF ₃ )

X L M R Mp (° C) H H H 4-C1 238-241 (Dec) H H 2-C1 4-C1 202-204 H H H 4-F > 240 H H H 3-NO ₂ > 250 H H H 3-Cl > 200 H H 3-F 5-F > 235 H H H 2-F 131-133 H H H 4-OCF ₂ CHF ₂ 169-172

The example

Testing of insecticidal and acaridic effects The tests are carried out with technical substances at 27 ° C:

Examination of Spodoptera eridania:

Sieva lima bean leaf is cut to a size of 7-8 cm and immersed in a mixed suspension of the test drug for 3 seconds and then dried under a lid. The leaf was placed on a wet filter paper in a 100x10 mm Petri dish and placed on 10 third instar caterpillars. After five days, we investigate death, loss of nutrition, or abnormal molting.

Examination of Spodoptera eridania with a residual effect of 7 days:

Plants treated in the above manner were kept in a greenhouse for 7 days under sunlight with 14 hours of daylight. After 7 days, the leaves are subjected to the test described above.

Aphisfabae:

One spotted flowering plant (Tropaleolum sp.), 5 cm in height, was inoculated with about 100-200 experimental animals one day before the test. The pots are placed on a rotating disk at 4 rpm and sprayed with the test compound at 154 DeVilbiss for two turns. The spray nozzle is held about 15 cm from the plant and directed to spray the plant and animals completely. The treated pots are placed on their side in white enamel trays and examined for death after two days.

Examination of Tetranachus urticae (P-resistant strain): Bean plants of the Sieva lima type are grown up to 7-8 cm in the first leaf condition and cut back so that only one plant remains per pot. Cut a small piece of the leaf from the main colony and place it on the leaves of the test plants. This operation is performed approximately 2 hours prior to treatment to allow the test animals to climb onto the test plant and lay eggs there. The size of the cut is chosen so that there are about 100 animals per leaf. Before treatment, this leaf piece is removed and discarded. The infected plants are immersed in a mixed formulation of the test drug for 3 seconds and then dried under cover. After two days, the first leaf is examined for mortality. The second leaf is kept on the plant for an additional 5 days and then examined for egg and / or freshly hatched larvae.

Diabrotic undecimpunctata howard's water test:

Place 1 cm ^{3 of} fine talc in a 1 ml wide-mouthed glass jar. Pipette 1 ml of the appropriate concentration of acetone suspension into the talc to give 1.25 mg and 0.25 mg of active ingredient per dish. The acetone is evaporated with slight air flow. The dry talc is loosened and 1 cm ^{3 of} millet kernel and 25 ml of wet soil are added as feed. Cover the dishes and mix thoroughly. Subsequently, 10 test animals are placed in each vessel and the larvae are provided with sufficient air exchange. After 6 days, test for mortality. Missing larvae are considered dead because they decompose quickly and cannot be found. The concentration of active substance used in the study corresponds to the application rates of about 50 kg / ha and 10 kg / ha.

Evaluation Scale:

0 no effect 9 100% decay 1 10-25% mortality R reduced nutritional tion. 2 26-35% mortality 3 36-45% mortality

0 no effect 9 100% decay 4 46-55% mortality 5 56-65% mortality 6 66-75% mortality 7 76-85% mortality 8 86-99% mortality

Table 1

agent A. fabae S. eridania T. urticae D. undecimpunctata howardi 100 ppm 1000 ppm 100 ppm 7 days 300 ppm 50 kg / ha 4,5-dichloro-2-phenyl-pyrrole-3-carbonitrile 0 9 8.5 9 0 0 4,5-dichloro-2- (p-chlorophenyl) pyrrole-3-carboxylic carbonitrile 0 9 9 9 0 55 4,5-dichloro-2- (3,4-dichlorophenyl) pyrrole-3- carbonitrile 0 9 9 9 0 0 4,5-dichloro-2- [p- (trifluoromethoxy) phenyl] - pyrrole-3-carbonitrile 7.5 9 9 9 9 7.7 4,5-dichloro-2- (p-chlorophenyl) pyrrole Title-3-carboxylic carbonitrile 0 9 9 0 0 2- (p-bromophenyl) -4,5-dichloro-pyrrole-3-carboxylic carbonitrile 0 9 9 8 0 4,5-dichloro-2- (a, a, a-trifluoro-p-tolyl) -pir- Roi-3-carbonitrile 0 9 9 9 8 4,5-dibromo-2- (p-chlorophenyl) pyrrole-3-carboxylic carbonitrile 0 9 4 0 0 4,5-dibromo-2- (p-chlorophenyl) pyrrole Title-3-carboxylic carbonitrile 0 9 9 0 0 4,5-dibromo-2- (a, a, a-trifluoro-p-hydantoin) - pyrrole-3-carbonitrile 0 9 9 9 9 4,5-dichloro-2- (2,4-dichlorophenyl) pyrrole-3- carbonitrile 0 9 9 9 0 0 4,5-dibromo-2- (2,4-dichlorophenyl) pyrrole-3- carbonitrile 0 9 9 9 0 0 4,5-dichloro-2- (m-chlorophenyl) -pmol-3-carboxylic carbonitrile 0 9 9 9 0 0 2,3-dichloro-4-nitro-5-phenyl-pyrrole 0 9 9 9 0 0 2,3-dichloro-5- (p-chlorophenyl) -4-nitropÍrroI 0 9 9 9 7.5 8 2,3-dibromo-5- (p-chlorophenyl) -4-nitropirroI 0 9 9 9 0 7.5 _2> 3-dibromo-4-nitro-5-phenylpyrrole 0 9 9 9 0 0 2,3-dichloro-5- (3,4-dikI6r-phenyl) -4-nitro- pyrrole 0 9 9 9 0 0 2- (p-Brot-phenyl) _-4-r 5 dikl6r-3-nitropyrrole 8 9 9 9 8.5 8 2,3-dichloro-4-nitro-5- (a, a, a-trifluoro-p- tolyl) -ptnol 8.3 9 9 9 9 8.3

HU 204,971 Β

Example B

Investigation of insecticidal activity

Examination of Heliothis virescens:

Cotton dotyledons are immersed in the test composition and dried under a cover. After drying, cut into squares and place 10 pieces each in a 30 ml plastic container containing a dental swab piece of 5-7 mm in length. One test animal is added to each vessel and covered with a cardboard lid. After 3 days, mortality and loss of nutrition were examined.

Empoasca abrupta:

Sieva lima bean plants are grown to a length of about 5 cm, immersed in a mixed formulation of the test drug for 3 seconds, and finally dried under a lid. Place the leaf on a damp filter paper in 100x10 mm Petri dishes. About 10 adult test animals are added to each well and assayed for death after 3 days.

Blattella germanica:

0.1% baits were prepared by pipetting 1 ml of a 1000 ppm acetone solution of the test substance into 1 g of corn flour into a 30 ml wide mouth glass jar. The bait is dried with a gentle air stream. The bait is then placed in a half-liter wide mouth Mason dish and 10 adult male test animals are added. Cover the bottle and place a piece of wool dipped in 10% honey on the lid. Mortality was assessed after 3 days.

Blattella germanica, residual effect study:

ml of 1000 ppm acetone drug solution is pipetted slowly to the bottom of a 150 x 15 mm Petri dish so as to distribute as uniformly as possible. After the layer has dried, 10 adult male test animals are placed in the container and covered. Mortality was assessed after 3 days.

Investigation of systemic effects of Spodoptera eridania:

0.1 g of the test substance, 0.2 g of Emulphor-EL-620 emulsifier, 10 ml of acetone and 90 ml of water were prepared as an emulsion. This was diluted ten-fold with water to give an emulsion of 100 ppm. If necessary, this emulsion is diluted ten times with water. Sieva lima leaf-type bean plants are grown to a height of 7-8 cm, cut off about 3 cm above the soil to avoid infecting the soil bacteria, which would interfere with the test. The cut stalk is placed in the active ingredient emulsion and the stems are wrapped in a woolen piece to keep it away from the bottom of the vessel and to reduce evaporation. The pots are maintained for 3 days at 27 ° C to ensure uptake of the active ingredient into the plant. A leaf was then removed from the plant and placed in a 10x 10 mm petri dish together with 10 test animals. After three and five days, the mortality and the reduction in nutrition are examined.

Examination of Empoasca abrupta:

0.1 g of the test substance, 0.2 g of Emulphor-EL-620 emulsifier, 10 ml of acetone and 90 ml of water are prepared in an erosion composition. This is diluted ten-fold with water to give an emulsion of 100 ppm. This is diluted ten times with water, if desired. Sieva lima broadleaf bean plants are grown to a length of 7-8 cm and then cut 3 cm above the soil to avoid contamination of soil bacteria which would interfere with the test. The cut stems are placed in the drug emulsion and each stalk is wrapped in a piece of wool to keep it away from the bottom of the pot and to reduce evaporation. The pots are maintained for 3 days at 27 ° C to ensure uptake of the active ingredient into the plant. A leaf is then cut off and placed in a 100x10 mm Petri dish and assayed as described above.

The scale described in the previous example is used for evaluation.

II. spreadsheet

agent E. abrupta H. virescens Systemic effect R. germanica 100 ppm 1000 ppm 100 ppm S. eridania E.abrupta bait Maradékha- OTING 100 ppm 100 ppm 1000 ppm 1000 ppm 4,5-dichloro-2-phenyl-pyrrole-3-carboxyphenyl rIL 0 8 0 - 0 0 4,5-dichloro-2- (p-chlorophenyl) pyrrole-3- carbonitrile 0 9 8.5 9 0 0 7 4,5-dichloro-2- (3,4-dikl6r-phenyl) -pir- Roi-3-carbonitrile 0 9 9 9 0 7 7 4,5-dichloro-2- [p- (trifluoromethoxy) -phenyl- phenyl] pyrrole-3-carbonitrile 9 9 9 9 9 0 8

HU 204,971 Β

agent E.abrupta H. virescens Systemic effect R. germanica 100 ppm lOOOppm 100 ppm S. eridania E. abrupta bait Maradékha- OTING 4,5-dichloro-2- (p-cyanobiphenyl-phenyl) -pyrrole-3- carbonitrile 0 0 7 0 0 0 2- (p-Bronophenyl) -4-dichloro-pyrrole- 3-carbonitrile Q 9 9 - - 0 0 4,5-dichloro-2- (a, a, a-trifluoro-p-Tolyl) - pyrrole-3-carbonitrile 9 9 9 - 9 0 9 4,5-dibromo-2- (p-chlorophenyl) pyrrole 3-carbonitrile 0 0 7 0 0 0 4,5-dibromo-2- (p-chlorophenyl) pyrrole 3-carbonitrile 0 9 9 - 0 0 0 4,5-dibromo-2- (a, a, a-trifluoro-p-to- Hl) pyrrole-3-carbonitrile 9 9 9 - 9 0 9 4,5-dichloro-2- (2,4-dichlorophenyl) -pir- Roi-3-carbonitrile 0 9 9 - 0 0 0 4,5-dibromo-2- (2,4-dichlorophenyl) -pir- pyrrole-3-carbonitrile 0 0 - 0 0 0 4,5-dichloro-2- (m-chlorophenyl) pyrrole-3- carbonitrile 0 9 9 - 0 0 0 2,3-dichloro-4-nitro-5-phenyl-pyrrole 0 9 6 8 9 0 4 2,3-dichloro-5- (p-chlorophenyl) -4-nitro- pyrrol 8.5 9 8 9 0 9 9 2,3-dibromo-5- (p-chlorophenyl) -4-nitro- pyrrole 0 8.5 6 0 0 0 9 2,3-dibromo-4-nitro-5-phenylpyrrole 0 8.5 0 9 0 0 0 2,3-dichloro-5- (3,4-dikI6r-phenyl) -4-fertilis- ropinol 9 9 9 9 9 0 9 2- (p-bromophenyl) -44-dichloro-3-nitro- pyrrole 8 9 6.5 9 9 0 9 2,3-dikI6r-4-nitro-5-a, a, a-trifluoro- p -tolyl) pyrrole 9 9 8 9 9 0 9

Example C

A) Investigation of Nematicide effect

Maintenance of the breed:

C. elegans (Bristol strain, J. Lewis) was grown on E. coli on NG agar plates at 20 ° C. Every week a new culture is made.

Test worms were washed with fresh Ascaris Ringers Solution (FARS) from a 4-5 day culture. The animals were further washed with FARS containing gentamicin to reduce bacterial infection, and the wash solution was separated by centrifugation. This procedure is repeated three times. The washed animals are added to C. briggsae maintenance medium (CbMM from GIBCOa) containing 600 units of gentamicin and 0.5 mg of mycostatin per ml.

Assays are performed using a mixture of three compounds combined with a high-performance screening program to reduce cost. The active compounds are dissolved in acetone and diluted with an equal volume of water. The drug concentration is 150 ppm. The test preparation was micropipetted (25 microliters) into a well of a 96-well sterile tissue culture plate (COSTAR) and the solvent was allowed to evaporate. The treated plate is either used directly or stored in a freezer to avoid side effects.

Freshly prepared C. elegans (50 micrograms) was prepared by CbMM in each well and some control wells. The cultured plates were incubated at 20 ° C.

The effect was examined by an autopsy microscope after 4.24 and 48 hours after immersion. Immediately after the measurement, the motility of the experimental animals is examined. The assay is conducted subjectively but semi-quantitatively on adult animals and larvae. The rating is as follows:

8 no mobility significantly reduced mobility in about 95% of animals 6 reduced mobility slightly decreased mobility

0 normal mobility, same as control.

HU 204,971 Β

Other possible effects such as death, rigidity, contraction, twisting, paralysis, abnormal jerking, reduced population after 48 hours, or other deviations from normal behavior are readily apparent.

Conducting an elegant examination of Caenorabditis:

Day 0 Inoculation of E. coli-NG agar plate at 3050 ° C. elegant, incubation at 20 ° C

Day 4 New C. elegant population collection, antibiotic wash, transfer to CbMM, addition of C elegant (25-100 UL) to treated well (a), effect assay 4 hours post immersion

Day 5 effect test

Day 6 effect test.

(a) = Treated hole can be prepared fresh or earlier and stored in a freezer. The test results are shown in Annex III. Table.

B) Investigation of Meloidogyne incognita

The test animals were grown in a fireball-type tomato greenhouse. The eggs are removed from the infected root surface and allowed to hatch on wet filter paper for 24 hours. The hatched larvae fall into the water next to the paper. The test larvae were transferred to a cell plate containing 300 ppm of the test compound in the form of a 3% acetone solution in a volume of approximately 10 larvae per cell. The infected plates were maintained at 27 ° C and examined for death after 24 hours. The measurement data are given in Annex III. Table.

Table 111

C. elegant 150ppm M. incognita 300 ppm larva adult 4,5-dichloro-2- [p- (trifluoromethoxy) phenyl] pyrrole-3-carbonitrile - - 4 4,5-dichloro-2- (a, a, <x-trifluoro-p-tolyl) pyrrole-3-carbonitrile 9 9 5 4,5-dibromo-2- (a, a, a-trifluoro-p-tolyl) pyrrole-3-carbonitrile 9 9 0 2,3-dichloro-4-nitro-5-phenylpyrrole 0 0 9 2,3-dichloro-5- (p-chlorophenyl) -4-nitropyrrole 9 9 9 2,3-dichloro-5- (3,4-dichlorophenyl) -4-nitropiiTol 9 9 0 2- (p-bróni'fenil) -4,5-dichloro-3-nitropyrrole 9 9 6 2,3-dikl6r-4-nitro-5- (a, a, a-trifluoro- p -tolyl) pyrrole 9 9 0

(c) Spodoptera eridania,

(d) Blattella germanica.

Example D The evaluation is made on the scale given. THE

In the same manner as described in Examples A and B, the new measurement results 40 are tested in Table IV. Table.

for two or more replicates, average) Empoasca abrupta, give the result.

(b) Heliothis virescens, / V. spreadsheet

agent the) b) c) systemic effect residual effect 100 ppm 1000 ppm 100 ppm 1000 ppm 100 ppm 7 days c) 100 ppm the) 100 pPM d) 1000 pPM 2,5-dichloro-4-phenyl-pyrrole-3-carbonitrile 0 6 0 9 9 8 0 0 0 2,3-dibromo-4-nitro-5-phenylpyrrole 0 9 0 9 9 - 9 0 0 4-chloro-2- (p-chlorophenyl) pyrrole-3-carbonitrile 0 9 2 9 9 - 9 9 0 4,5-dichloro-2- (p-chlorophenyl) pyrrole-3-carbonitrile 0 0 0 9 9 - 7 0 0

HU 204971 Β

agent the) b) c) systemic effect residual effect 100 ppm 1000 ppm 100 ppm 1000 ppm 100 ppm 7 days c) 100 ppm the) 100 ppm d) 1000 ppm 5-bromo-2- (p-chlorophenyl) pyrrole-3-carbonitrile 0 9 0 9 9 - - 0 0 4,5-dichloro-2- (3,4-dichloro-phenyl) -l- (ethoxymethyl} - pyrrole-3-carbonitrile 9 9 9 9 9 9 5 0 7 4,5-dichloro-2- (p-chlorophenyl) -l-methyl-pyrrole-3-carboxylic carbonitrile 0 9 9 9 9 9 - 0 9 p- (45-dichloro-3-cyano-pyrrol-2-yl) -metil'benzoát 0 4R8 0 9 0 - 3 0 0 4,5-dibromo-2- (3,4-dichlorophenyl) pyrrole-3-carbo- nitrile 0 9 0 9 9 9 0 0 0 4,5-dichloro-2- (a, a, a-trifluoro-m-tolyl) -piiTol-3-carboxylic carbonitrile 0 9 9 9 9 9 9 0 9 4 ₁ 5-dichloro-2- (3,4-dichlorophenyl {chloro-phenyl) -l-ethyl-pyrrole-3-carboxylic carbonitrile 0 9 9 9 9 9 9 9 0 4,5-dichloro-2- (3,4-difluorophenyl) -pinoI-3-carboxyphenyl rIL 0 9 9 9 9 9 9 9 0 4,5-dichloro-2- (3,4-dichloro-phenyl) -l-methyl-pyrrole-3- carbonitrile 0 9 9 9 9 9 9 9 9 4,5-dichloro-2- [p- (methyl-sulfonyl) phenyl-pyrrole-3- carbonitrile 0 - 0 7 0 0 9 9 0 4,5-dibromo-l-methyl-2- (a, a, a-trifluoro-p-tolyl) -pir- Roi-3-carbonitrile 0 9 8 9 9 9 9 9 8.5 4,5-dichloro-2- (p-fluorophenyl) pyrrole-3-carbonitrile 0 9 9 9 9 9 9 9 0 4,5-dibromo-2- (3,4-difluorophenyl-phenyl) -pi7rol-3-carbo- nitrile 0 9 9 9 9 9 4.5 4.5 0 4,5-dibromo-2- (p-fluorophenyl) pyrrole-3-carbonitrile 0 9 9 9 9 9 0 0 0 4,5-dibromo-2- (p-nitrophenyl) pyrrole-3-carbonitrile 0 9 6 9 9 4 4.5 9 9 4,5-diki <5r-2- (p-nitrophenyl) pyrrole-3-karbónitrH 0 9 7 9 9 9 4.5 4.5 9 l-benzyl-4 ^ dibromo-2- (a, a, a-trifluoro-p-tolyl) - pirrof-3-carbonitrile 9 9 9 9 9 9 9 6 0 4,5-dichloro-2- (p-cyanophenyl) pyrrole-3-carbonitrile 0 9 8 9 9 0 0 5 4,5-dibrótn-2- [p- (methylsulfonyl) phenyl] -pin-ol 3- carbonitrile 0 2 - 9 0 - 0 0 0 4,5-dibromo-2- (p-kJ6r-phenyl) pyrrole Title-3-carbonitrile 0 9 7 9 9 - 0 0 0 4,5-dichloro-2- (3,4-dichloro-phenyl) -l- [2- (methylthio) - ethyl] pyrrole-3-carbonitrile 0 8 5 9 0 - 9 0 0 l-methyl-4,5-dichloro-2- (3,4-dichlorophenyl [chloro-phenyl) -pyrrole-3- carbonitrile 7 7 0 9 0 - 9 0 0 4,5-dichloro-l-methyl-2- (a, a, a-trifluoro-p-Toulon) -pir- pyrrole-3-carbonitrile 9 9 9 9 9 0 9 9 9 5-bromo-4-chloro-2- (p-chlorophenyl) pyrrole-3-carboxyphenyl ril 2.5 - 9 9 9 9 0 6 9 2,3-dichloro-5- (3,4-dichloro-phenyl) -l- (ethoxymethyl) -4- nitropyrrole 6 5 0 9 9 - 9 9 9 4 br6m-5-chloro-2- (p-chlorophenyl) pyrrole-3-carboxyphenyl ril 0 9 9 9 9 9 7 0 9 _l-benzyl-4-r 5-dichloro-2- (3,4-dichlorophenyl) -pyrrole-3-carbonitrile 0 9 0 9 9 5.5 9 9 2

HU 204,971 Β

agent the) b) c) systemic effect for today- dékha- OTING 100 ppm 1000 ppm 100 ppm 1000 ppm 100 ppm 7 days c) 100 ppm the) 100 pPM d) 1000 pPM ethyl 2,3-dichloro-5- (3,4-dichlorophenyl) -4-cyano-pyrrole 1-acetate 0 9 4 9 9 7 9 0 0 4,5-dichloro-l- (ethoxymethyl) -2- (a, a, a-trifluoro-p-to- yl) pyrrole-3-carbonitrile 9 9 9 9 9 9 9 9 9 3-bromo-5- (3,4-dichlorophenyl) pyrrole-2,4-dikarbo- nitrile 0 9 8.5 9 9 9 5 0 9 4,5-dichloro-2- (3,4-dichloro-phenyl) -l- (2-propynyl) -pir- Roi-3-carbonitrile 8 9 9 9 9 9 9 9 9 4,5-dibromo-3- (p-kl6r-phenyl) -piiTOl-2-karbonitnl 0 9 3 9 9 9 0 0 0 5- (3,4-dichlorophenyl) pyrrole-2,4-dicarbonitrile 7 9 9 9 9 9 5 9 7 5-bromo-4-chloro (3,4-dichlorophenyl) pyrrole-3-carbo- nitrile 0 9 9 9 9 9 0 6 9 4,5-dibromo-3- (p-chlorophenyl) -l-methyl-pyrrole-2-carboxylic carbonitrile 0 - - 9 9 0 0 0 9 2-bromo-5-phenyl-pyrrole-3,4-dicarbonitrile 0 2 0 9 0 9 0 '0 0 4-bromo-2-phenyl-5- (trifluoromethyl) pyrrole-3-carbo- nitrile 0 9 9 9 9 9 9 9 0 2- (3,4-dichlorophenyl) -5-nitro-pyrrole-3-carbonitrile 7 9 0 9 9 9 0 0 0 4-bromo-2- (3,4-dichlorophenyl) -5-nitropyrrole-3-carboxylic carbonitrile 0 5 0 9 0 3 0 0 0 2,4-dibromo-5-phenyl-pyrrole-3-carbonitrile 0 9 9 9 9 9 0 0 0 2- (3,4-dichlorophenyl) -4,5-diiodo-pyrrol-3-karbomtril 0 9 9 9 9 9 5 7 9 2,3-dibromo-5- (p-chlorophenyl) -1-ethoxymethyl-4-nitropyrrole 9 9 9 9 9 9 9 5 9 l-benzyl-2,3-dibromo-5- (p-chlorophenyl) -4-nitropyrrole 0 4 0 9 8 0 9 9 3 2,3-dibromo-5- (p-chlorophenyl) -1-methyl-4-nitropyrrole 0 8 7 9 9 '7 0 4 0 4,5-dibromo-2- [p- (trifluoromethoxy) phenyl] pyrrole-3- carbonitrile 9 9 9 9 9 9 9 0 0 4,5-dichloro-l- (ethoxymethyl) -2- [p- (trifluoromethoxy) - phenyl] pyrrole-3-carbonitrile 9 9 9 9 9 9 9 9 9 5- (p-chlorophenyl) pyrrole-2,4-dicarbonyl tryl 3 9 9 9 9 9 0 0 8 l-benzyl-4,5-dichloro-2- [p- (trifluoromethoxy) phenyl] - ρϊσοΙ-3-carbonitrile 9 9 0 9 9 9 9 9 0 4,5-dichloro-2- (p-chlorophenyl) -l- (ethoxymethyl) pyrrole-3-carbonitrile 8.5 9 9 9 9 9 9 9 9 4,5-Dichloro-2- (3,4-dichlorophenyl) -1- (2-hydroxyethyl) pyrrole-3-carbonitrile 0 9 2 9 9 9 0 9 0 2- (p-chlorophenyl) -5-nitro-pyrrole-3-carbonitrile 7 9 0 9 0 7 0 9 0 4-bromo-2-p-chlorophenyl) -5- (trifluoromethyl) pyrrole-3- carbonitrile 9 9 9 9 9 9 9 9 9 4-bromo-2- (p-chlorophenyl]) - 5-nitropyrrole-3-carboxyphenyl ril 0 9 0 9 9 9 0 7 0 3-bromo-5- (p-chlorophenyl) pyrrole-2,4-dicarbonitrile 6 8 5 9 9 9 0 3 9 4,5-Dichloro-2- (3,4-dichlorophenyl) pyrrole-1,3-dicarbonitrile 0 9 0 9 9 9 0 0 9 l - [(benzyloxy) methyl] -4,5-dichloro-2- (3,4-dichloro-Fe phenyl) pyrrole-3-carbonitrile 5 9 0 9 9 9 9 9 0

HU 204971 Β

agent the) b) c) systemic effect residual effect 100 ppm 1000 ppm 100 ppm 1000 ppm 100 ppm 7 days c) 100 ppm the) 100 ppm d) 1000 pPM 4,5-dichloro-2- (2,4-dichloro-5-fluorophenyl) pyrrole-3- carbonitrile 4 5 0 9 9 9 9 0 9 5- [p- (trifluoromethoxy) phenyl] pyrrole-2,4-dikarbo- nitrile 7 7 0 9 9 9 8 0 8 4,5-dichloro-I - [(p-chlorophenoxy) methyl] -2- (3,4-dictator IOR-phenyl) -pyrrolidine-3-karfaonitril 0 8 0 9 9 9 9 9 0 4,5-dichloro-2- (3,4-dichloro-phenyl) -l- (3-iodo-2-propionic phenyl) pyrrole-3-carbonitrile 9 9 0 9 9 9 9 0 0 5- (3,4-dichlorophenyl) -4-nitropiffoI-2-carbonitrile 9 9 9 9 9 9 0 9 9 2,4-dibromo-5- (p-chlorophenyl [) - pyrrole-3-carbonitrile 0 9 9 9 9 9 9 0 0 3-bromo-5- [p- (trifluoromethoxy) phenyl] pyrrole-2,4- dikarbonltril 9 9 ⁰ 9 9 9 9 0 9 3-bromo-5- (3,4-dichlorophenyl) -4-nitropyrrole-3-carboxylic quinolinecarbonitrile 9 6 0 9 9 9 0 0 0 4-bromo-2- (p-chlorophenyl) -l-methyl-5- (trifluoro-me- methyl) pyrrole-3-carbonitrile 9 9 0 9 9 9 0 0 9 3,4-dibrófn-5- (3,4-dichlorophenyl) pyrrole-2-carbo- the nitrile 0 9 9 9 9 9 0 0 9 2- (3,4-dikl6r-phenyl) -5-trifluoromethyl) pyrrole-3-carboxylic carbonitrile 0 9 9 9 9 9 0 0 9 5- (trifluoromethyl) -2- (a, a, a-trifluoro- p -tolyl) pyrrole 3-carbonitrile 7 9 9 9 9 9 0 0 9 2,5-dibromo-4- (p-chlorophenyl) pyrrole-3-RarbonitriI 0 9 0 9 9 9 0 0 9 3,5-dibromo-4- (p-chlorophenyl) pyrrole-2-carbonitrile 0 9 3 9 9 9 0 0 0 2-p-tolH-5- (trifluoromethyl) pyrrole-3-carbonitrile 0 9 0 7.5 0 0 0 0 0 4-bromo-2-p-tolyl-5- (trifluoromethyl) pyrrole-3-carboxylic carbonitrile 0 9 6 9 9 9 - - 0 4-bromo-2- (p-chlorophenyl) -l- (ethoxymethyl-5- (triflu- Trifluoromethyl) pyrrole-3-carbonitrile 9 9 9 9 9 9 0 Q 9 4-bromo-2- (3,4-dichlorophenyl) -5- (trifluoromethyl) -pir- pyrrole-3-carbonitrile The 9 9 9 9 9 9 0 0 9 5- (a, a, a-trifluoro-p-tolyl) pyrrole-2,4-dicarbonitrile 9 9 9 9 9 9 7 9 0 l-methyl-3- (a, a, a-trifluoro-p-hydantoin) pyrrole-2,4-di- carbonitrile 0 3 0 9 0 0 0 0 0 4-bromo-5- (trifluoromethyl) -2- (alpha, alpha, alpha-trifluoro- p-to- Hl) pyrrole-3-carbonitrile 9 9 9 9 9 9 0 0 9 Br6m-3-I-methylpiperidin-5- (a, a, a-trifluoro-p-tolH) -pirroI- 2,4-dlkarbonítril 0 7 0 9 0 0 - - 0 4,5-dichloro-2- (a, a, a-trifluoro-p-tolyl) pyrrole-I, 3-di- carbonitrile 9 9 9 9 9 - - - 9 3-bromo-5- (a, a, a-trifluoro-p-tolyl) pyrrole-2,4-di- carbonitrile - - - 9 - - - - -

Claims (5)

PATENT CLAIMS An insecticidal, acaricidal and nematicidal agent, comprising an arylpyrrole derivative of general formula (I) as an active ingredient, wherein X is chloro, bromo, iodo or trifluoromethyl, Y represents a chlorine, bromine or iodine atom and a trifluoromethyl or cyano group, W is cyano or nitro, A is hydrogen, (C 1 -C 4) alkyl optionally substituted with halogen, hydroxy, (C 1 -C 4) alkoxy or (C 1 -C 4) alkylthio, phenyl, phenoxyl or (C 1 -C 2) alkoxyphenyl; C4 -C4alkylmethyl, C3-4alkenyl which may be optionally substituted by halogen, cyano, C3-4alkynyl optionally substituted by one halogen or C1-4alkylaminoalkyl in its alkyl moieties; carbonyl, L is hydrogen, fluorine, chlorine or bromine, Me and R are each independently hydrogen, (C 1 -C 3) alkyl, (C 1 -C 3) alkoxy, (C 1 -C 3) alkylsulfonyl, cyano, fluoro, bromo or iodo, nitro, trifluoromethyl, R ₁ CF ₂ Z or R _{2 is} CO, or the adjacent M and R, together with the carbon atom to which they are attached, form a ring in which MR is a) Z is oxygen, R 1 is fluoro or CHF ₂ , R ₂ is C 1-3 alkyl, 0.1 to 95% by weight with solid carriers and / or liquid diluents and optionally surfactants. (Priority: June 23, 1988) Insecticidal, acaricidal and nematicidal agent according to claim 1, characterized in that it contains as an active ingredient an arylpyrrole derivative of formula (II): X, Y, W, A, L, M and R are as defined in claim 1. (Priority: July 29, 1987). 3. A process for the preparation of arylpyrrole derivatives of the general formula (II) in which: X is chloro, bromo, iodo or trifluoromethyl; Y is chloro, bromo or iodo, and trifluoromethyl or cyano, W is cyano or nitro, A is hydrogen, (C 1 -C 4) alkyl optionally substituted with halogen, hydroxy, (C 1 -C 4) alkoxy or (C 1 -C 4) alkylthio, phenyl, phenoxy or (C 1 -C 2) alkoxyphenyl; C4 -C4alkylmethyl, C3-4alkenyl which may be optionally substituted by halogen, cyano, C3-4alkynyl optionally substituted by halogen or alkyl groups thereof having from 1 to 4 carbon atoms carbonyl, L is hydrogen, fluorine, chlorine or bromine, M and R are independently hydrogen, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 alkylsulfonyl, cyano, fluoro, chloro, bromo or iodo, nitro, trifluoromethyl, R _{1 is} CF ₂ Z, R ₂ CO, or the adjacent M and R together with the carbon atom to which they are attached form a ring in which MR is a) Z is oxygen, characterized in that it is a benzoylacetonitrile or alpha-nitroacetophenone derivative of the formula wherein L, M, R and W are as defined in the foregoing alkoxy-2,2-dialkoxy group having 1 to 4 carbon atoms. ethylamine at elevated temperature and the resulting alkoxy of formula (XXIV) contains alpha- (2,2-dialkoxyethylamino) -beta-cyano-styrene or alpha- (2,2-dialkoxyethylamino) having from 1 to 4 carbon atoms. ) -beta-nitrostyrene derivative of the formula L, M, R and W are treated with a mineral or organic acid as defined herein, and the resulting compound of formula (X) is reacted with a halogenating agent or a pseudohalogenating agent to introduce a substituent X and Y, and the resulting The compound of formula (I) is optionally reacted with a compound of formula A-Hal, wherein A is as defined herein, Hal is halogen, and A is other than hydrogen. (Priority: 29.07.1987) A process according to claim 3, wherein the benzoylacetonitrile or alpha-nitroacetophenone derivative is reacted with 2,2-dialkoxyethylamine alone or in the presence of an inert organic solvent. (Priority: July 29, 1987) 5. The process of claim 3, wherein the alpha- (2,2-dialkoxyethylamino) -beta-cyano-styrene or alpha- (2,2-dialkoxyethylamino) -beta- the nitrostyrene derivative is treated with hydrochloric acid, hydrobromic acid or trifluoroacetic acid.