FI91523B - Arylpyrroles useful as insecticides, acaricides and nematicides - Google Patents

Description

, 915/3

This invention relates to novel arylpyrrole compounds which are highly effective insecticides, acaricides and nematicides useful in the control of insecticides, mites and nematodes. to protect both growing and harvested crops from 10 pests caused by said pests.

U.S. Patent 3,428,648 describes pyrrolinitrine as an antifungicidal compound, but makes no mention of insecticidal activity. EP Patent Application 80,051 describes a number of tetrazoles useful as antibacterial or antifungal agents and broadly covers certain pyrroles, imidazoles, pyrazoles and tetrazoles. The pyrroles may further be substituted with a phenyl or 3-chloro-2-nitrophenyl group together with a halogen atom and a nitro group.

In all cases, the structures are substituted on the nitrogen atom by a triiodallyl or iodopropargyl group. The publication does not contain examples of the tetrasubstituted pyrrole type or insecticidal activity of the present invention. In addition, EP patents 25,130,149 and 182,737 describe certain pyrroles which have been reported to be useful for fungicidal or bactericidal purposes, but which also make no mention of insecticidal activity.

The invention relates to a compound of structural formula 30 I.

35 N

A

wherein X is F, Cl, Br, I or CF 3; Y is F, Cl, Br, I, CF 3 or CN; H is CN or NO 2; and A is H; C 1-4 alkyl optionally substituted with 2 to 15 halogen atoms, one hydroxy, one C 1-4 alkoxy or one C 1-4 alkylthio, one phenyl optionally substituted with C 1-3 alkyl or C 1-3 alkoxy or mono- three halogen atoms, one phenoxy optionally substituted with one to three halogen atoms, or one benzyloxy optionally substituted with one halogen substituent; C 1-4 karbalkoksimetyyli; C3-4 alkenyl optionally substituted with one to three halogen atoms; cyano; C3-4 alkynyl optionally substituted with one halogen atom; di-iC ^ alkyl) amino-carbonyl; or C 4-6 cycloalkylaminocarbonyl; L is H, F, Cl or Br; and M and R are each independently H, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 alkylsulfonyl, cyano, F, Cl, Br, nitro, CF 3, CF 3 or R 2 CO, and when M and R are at adjacent positions, they may, together with the carbon atoms to which they are attached, form a ring in which MR denotes the structure:

20 O

and R 2 is C 1-3 alkyl or C 1-4 alkoxy.

The term C 4-6 cycloalkylaminocarbonyl denotes a C 4-6 cycloalkylamino group which is directly attached to the carbonyl group via a nitrogen atom.

A preferred group of novel arylpyrroles of this invention is represented by Formula II:

R

wherein A, L, M, R, W, X and Y are as described above. Another preferred group of novel arylpyrroles of this invention is represented by Formula III; 35? U \ J_ l y ^ n <111> 39 ι 5 e. 5 where A, L, M, R, W, X and Y are as described above.

Another preferred group of arylpyrroles of the invention is represented by formula IV:

Π '-R

10 wherein A, L, M, R, W, X and Y are as described above.

Yet another group of preferred arylpyrroles of this invention is represented by Formula V: 15 m *

20 R

wherein A, L, M, R, w, X and Y are as described above; and still other preferred arylpyrroles of the invention are represented by formulas VI and VII: '! p (VI) (VII) 35 wherein A, L, M, R, W, X and Y are as described above.

91 523 4

Preferred aryl pyrroles of the invention of formula I are those wherein A is hydrogen or C 1-4 alkoxymethyl; W is CN or NC 2; L is hydrogen or F; X and Y are each Cl, Br or CF 2; M is H, F, Cl or Br; and R is F, Cl, Br, CF3 or OCF-.

Preferred compounds of formula II which are particularly effective as insecticides, acaricides and / or nematicides are those in which A is hydrogen or C 1-4 alkoxymethyl; L is hydrogen; M is hydrogen, F, Cl 10 or Br; R is F, Cl, Br, CF 3 or OCF 3; W is CN and X and Y are each independently Cl, Br or CF3 ·

Other compounds of formula II which are very effective as insecticides, acaricides and / or nematicides are those in which A is hydrogen or C 1-4 alk-oxymethyl; L is hydrogen; M is hydrogen, F, Cl or Br; R is F,

Cl, Br, CF3 or OCF3; W is NC> 2 and X and Y are independently Cl, Br or CF3 ·

Illustrative of some of the insecticides, acaricides and nematicides of this invention are: 4,5-dichloro-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile; 4,5-dichloro-2- [E- (trifluoromethoxy) phenyl] pyrrole-3-carbonitrile; 4-bromo-5-chloro-2- (N-chlorophenyl) pyrrole-3-carbonitrile; 5-bromo-4-chloro-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile; 4,5-dichloro-2- (o-chlorophenyl) pyrrole-3-carbonitrile; 2- (£ -bromifenyyli) -4,5-diklooripyrroli-3-carbonitrile; 4,5-dichloro-2- (α, O, N, trifluoro-ε-tolyl) pyrrole-3-carbonitrile; 4,5-dibromo-2- (oC, N, N-trifluoro-ε-tolyl) pyrrole-3-carbonitrile; 4,5-dibromo-2- (o-chlorophenyl) pyrrole-3-carbonitrile; 4,5-dibromo-2- (N-chlorophenyl) pyrrole-3-carbonitrile; 4,5-dichloro-2- (2,4-dichlorophenyl) pyrrole-3-carbonitrile; 5,91523 4,5-Dibromo-2- (2,4-dichlorophenyl) pyrrole-3-carbonitrile; 2,3-dibromo-4-nitro-5-phenylpyrrole; 2- (iso-bromophenyl) -4,5-dichloro-3-nitropyrrole; 2,3-dichloro-4-nitro-5- (o, O, c, L-trifluoro-ε-tolyl) pyrrole; 4,5-dichloro-2- (m-chlorophenyl) pyrrole-3-carbonitrile; 4,5-dichloro-2- (E-chlorophenyl) pyrrole-3-carbonitrile; 4,5-dichloro-2-phenylpyrrole-3-carbonitrile; 2,3-dichloro-5- (E-chlorophenyl) -4-nitropyrrole; 2-bromo-3-chloro-5- (E-chlorophenyl) -4-nitropyrrole; 2,3-dibronyl-5- (E-chlorophenyl) -4-nitropyrrole; 2,3-dichloro-4-nitro-5-phenylpyrrole; 3-bromo-2-chloro-4-nitro-5- (oC, ol, α-trifluoro-ε-tolyl) -pyrrole; 5-chloro-2- (3,4-dichlorophenyl) -1- (methoxymethyl) -4- (trifluoromethyl) pyrrole-3-carbonitrile; 5-bromo-2- (m-fluorophenyl) -3-nitro-4- (trifluoromethyl) pyrrole; 2- (E-chlorophenyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile; 3-bromo-5- (m-fluorophenyl) -4-nitro-2- (trifluoromethyl) pyrrole; 4-bromo-2- (E-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) -1- (2-propynyl) -4,5-bis (tri-fluoromethyl) pyrrole-3-carbonitrile; 2- (2,5-difluorophenyl) -3-nitro-4,5-bis- (trifluoromethyl) pyrrole; 5 - [(trifluoromethoxy) phenyl] pyrrole-2,4-dicarbonitrile; 5- (£ -dimetyyliaminofenyyli) -4-nitropyrrole-2-carbonitrile; 3-bromo-5- (E-chlorophenyl) pyrrole-2,4-dicarbonitrile: 4-bromo-2- (E-chlorophenyl) -5-nitropyrrole-3-carbonitrile; 6 91 523 5- (E-methylthiophenyl) -3- (trifluoromethyl) pyrrole-2,4-dicarbonitrile; 1-allyl-4-nitro-5- (o, ali, trifluoro-ε-tolyl) -3- (trifluoromethyl) pyrrole-2-carbonitrile; 4-chloro-2- (p-chlorophenyl) pyrrole-3-carbonitrile; 2- (m-methanesulfonylphenyl) -4- (trifluoromethyl) pyrrole-3-carbonitrile; 2- (3-chloro-4-methylphenyl) -1-methyl-3-nitro-4- (trifluoromethyl) pyrrole; 2-phenylpyrrole-3,4-dicarbonitrile; 5- (p-etaanisulfinyylifenyyli) -4-nitropyrrole-3-carbo-nitrile; 2-bromo-5-phenylpyrrole-3,4-dicarbonitrile; 2-chloro-5- (3,5-dichlorophenyl) -4-nitropyrrole-3-carbo-15-nitrile; 1-benzyl-4-nitro-5- (E-chlorophenyl) -2- (trifluoromethyl) pyrrole-3-carbonitrile; 2-chloro-5- (m-bromophenyl) pyrrole-3-carbonitrile; 2-bromo-1- (E-chlorophenoxy) methyl-5- (E-chlorophenyl) -3-nitropyrrole; 2,4-dibromo-5-phenylpyrrole-3-carbonitrile; 5- (£ -bromifenyyli) -2,4-dichloro-3-nitropyrrole; 2-bromo-5- (3-bromo-4-methylphenyl) -1- (n-propyloxy) methyl-4- (trifluoromethyl) pyrrole-3-carbonitrile; 2-bromo-5- (E-chlorophenyl) -3-nitro-4- (trifluoromethyl) pyrrole; 5- / m (difluoromethoxy) fenyyli7-2- (trifluoromethyl) pyrrole-3-carbonitrile; 5- (2,3-dichlorophenyl) -1-methoxymethyl-3-nitro-2- (tri-fluoromethyl) pyrrole; 4-chloro-5- (β-naphthyl) -2- (trifluoromethyl) pyrrole-3-carbonitrile; 3-bromo-2- (3,4-dichlorophenyl) -4-nitro-5- (trifluoromethyl) pyrrole; 5- (2-bromo-5-ethylphenyl) -2,4-bis- (trifluoromethyl) pyrrole-3-carbonitrile; 7 91,523 1-ethyl-2- (E-fluorophenyl) -4-nitro-3,5-bis- (trifluoromethyl) pyrrole; (2,6-dichlorophenoxy) methyl-5- (m-chlorophenyl) pyrrole-2,3-dicarbonitrile; 5-nitro-5- (1'-trifluoro-ε-tolyl) pyrrole-2-carbonitrile; 4-chloro-5- (4-chloro-2-methylphenyl) pyrrole-2,3-dicarbonitrile; 4-bromo-5- (3,4-dibromophenyl) -2-nitropyrrole-3-carbonitrile; 1- [(1-methoxy) ethyl] -5- (p-chlorophenyl) -4- (trifluoromethyl) pyrrole-2,3-dicarbonitrile; 5- (E-isopropylphenyl) -2-nitro-4- (trifluoromethyl) pyrrole-3-carbonitrile; 4-chloro-5- (3,4-difluoromethylenedioxyphenyl) pyrrole-3-carbonitrile; 3-bromo-2- (3-chloro-4-cyanophenyl) -4-nitropyrrole; 1- (3,4-dichlorobenzyloxy) methyl] -2- (m-bromophenyl) pyrrole-4-carbonitrile; 2, (3,5-dichloro-4-methylphenyl) -4-nitro-3-trifluoromethylpyrrole; 2-phenylpyrrole-3,4-dicarbonitrile; 2- (2-bromo-4-chlorophenyl) -4-nitropyrrole-3-carbonitrile; 2-bromo-5-phenylpyrrole-3,4-dicarbonitrile; 5-chloro-2- (3,4-dibromophenyl) -1-methyl-4-nitropyrrole-3-carbonitrile; 2- (E-chlorophenyl-5- (trifluoromethyl) pyrrole-3,4-dicarbonitrile; 2- (o-bromophenyl) -4-nitro-5- (trifluoromethyl) pyrrole-3-carbonitrile; 3-bromo-5- (3-chloro-4-methoxy) pyrrole-2-carbonitrile, 3-bromo-5- (m-bromophenyl) -2-nitropyrrole, 3,4-dibromo-5- (3,4-dichlorophenyl) pyrrole-2- carbonitrile-35; 2- (3-chloro-4-cyanophenyl) -5-nitro-3,4-dichloropyrrole; 8,91523 3-chloro-1- (p-methoxybenzyl) -5- (3,4-difluorophenyl) - 4- (trifluoromethyl) pyrrole-2-carbonitrile, 3-bromo-5- (3,5-dibromo-ε-tolyl) -2-nitro-4- (trifluoromethyl) pyrrole, 1- (2,3 (3-trichloroallyl) -5- (E-chlorophenyl) -3- (trifluoromethyl) pyrrole-2-carbonitrile; 2- (E-iodophenyl) -5-nitro-4- (trifluoromethyl) pyrrole; 5- (m-Isopropylphenyl) -3- (trifluoromethyl) pyrrole-2-carbonitrile 3-Bromo-1-methyl-2- (3-fluoro-4-methylphenyl) -2-nitro-3- (trifluoromethyl) pyrrole, 5- (E-bromophenyl) -1-isopropyl-3,4-bis- (trifluoromethyl) pyrrole-2-carbonitrile, 2- (3,4-dichloro-4-methylthio) -5-n itro-3,4-bis- (trifluoromethyl) pyrrole; 5- (m-difluoromethoxyphenyl) pyrrole-2,3-dicarbonitrile; 5- (3-bromo-4-cyanophenyl) -2-nitropyrrole-3-carbonitrile; 4-chloro-1-methoxymethyl-5- (E-bromophenyl) pyrrole-2,3-dicarbonitrile; 4-bromo-5- (2,6-dichloro-4-methylthio) -2-nitropyrrole-3-carbonitrile; 1- (C (E-bromophenoxy) methyl) -5- (m-trifluoromethyl) -4-trifluoromethyl) pyrrole-2,3-dicarbonitrile; 5- (oC-naphthyl) -2-nitro-4- (trifluoromethyl) pyrrole-3-carbonitrile; 4-bromo-5- (3-bromo-4-trifluoromethylphenyl) pyrrole-2-carbonitrile; 3-chloro-2- (2,3-dichlorophenyl) -5-nitropyrrole; 5- (m-cyanophenyl) -3- (trifluoromethyl) pyrrole-2-carbonitrile; 2- (3-bromo-4-isopropoxy) -5-nitro-3- (trifluoromethyl) pyrrole; 5- (£-chlorophenyl) pyrrole-2,4-dicarbonitrile; 2- (3,4-dichlorophenyl) -5-nitropyrrole-3-carbonitrile; 3-bromo-5- (3,4-dichlorophenyl) pyrrole-2,4-dicarbonitrile; 4-bromo-2- (3,4-dichlorophenyl) -5-nitropyrrole-3-carbonitrile; 91523 5- (3,4-dibromophenyl) -3- (trifluoromethyl) pyrrole-2,4-dicarbonitrile; 2- (m-chlorophenyl) -5-nitro-4- (trifluoromethyl) pyrrole-3-carbonitrile; 5-bromo-3- (3,5-dichloro-4-difluoromethoxyphenyl) pyrrole-2-carbonitrile; 2-bromo-4- (2,5-dibromophenyl) -5-nitropyrrole; 2,3-dibromo-5- (E-chlorophenyl) pyrrole-5-carbonitrile; 2,3-dichloro-4- (3,5-difluorophenyl) -5-nitropyrrole; 5-bromo-3- (E-chlorophenyl) -1-hydroxyethyl-4- (trifluoromethyl) pyrrole-2-carbonitrile; 2-chloro-5-nitro-3- (trifluoromethyl) -4- (m-trifluoromethylphenyl) pyrrole; 3- (3-bromo-4-chlorophenyl) -5- (trifluoromethyl) pyrrole-2-carbonitrile; 3- (3-chloro-4-fluorophenyl) -2-nitro-5- (trifluoromethyl) pyrrole; 4-bromo-3- (E-chlorophenyl) -1-methylthiomethyl-5- (trifluoromethyl) pyrrole-2-carbonitrile; 3- (4-bromo-3-cyanophenyl) -4-chloro-2-nitro-5- (trifluoromethyl) pyrrole; 4- (£-chlorophenyl) -2,3-bis (trifluoromethyl) pyrrole-2-carbonitrile; 3, (2,3-dichlorophenyl) -2-nitro-4,5-bis- (trifluoromethyl) -25 pyrrole; 3- (3,4-dichlorophenyl) pyrrole-2,5-dicarbonitrile; 4- (2-bromo-4-methylphenyl) -5-nitropyrrole-2-carbonitrile; 3-bromo-4- (3,5-dichloro-4-methylthiophenyl) pyrrole-2,5-30 dicarbonitrile; • 4- (m-bromophenyl) -3-chloro-5-nitropyrrole-2-carbonitrile; 3- (E-acetamidophenyl) -4- (trifluoromethyl) pyrrole-2,5-dicarbonitrile; 4- (m-bromophenyl) -5-nitro-3- (trifluoromethyl) pyrrole-2-carbonitrile; 4-chloro-3- (3,4-dichlorophenyl) -1- (2-propenyl) pyrrole-2-carbonitrile; 10 91 523 3-Bromo-4- (E-dimethylaminophenyl) -5-nitropyrrole? 1- (3,4-dichlorobenzyl) -3- (E-chlorophenyl) -4- (trifluoromethyl) pyrrole-2-carbonitrile; 2-nitro-3- (E-tetrafluoroethoxyphenyl) -4- (trifluoromethyl-5H) pyrrole; 3- (3-bromo-4-i-propylphenyl) pyrrole-2,4-dicarbonitrile; 4- (E-ethylsulfonylphenyl) -5-nitropyrrole-3-carbonitrile; 5-bromo-1- (2-methoxyethyl) -4- (2,4,6-trichlorophenyl) -1-pyrrole-2,4-dicarbonitrile; 2-chloro-4- (2,3-dichlorophenyl) -5-nitropyrrole-3-carbonitrile; 3- (E-fluorophenyl) -5- (trifluoromethyl) pyrrole-2,4-dicarbonitrile; 4- (E-iodophenyl) -5-nitro-2- (trifluoromethyl) pyrrole-3-carbonitrile; 5-chloro-4- / £ - (N-methylacetamido) fenyyli7pyrroli-2-carbo-nitrile; 5-bromo-4- (o-bromophenyl) -1-propargylpyrrole-2-20 carbonitrile; 2-bromo-3- (o-bromophenyl) -5-nitropyrrole; 4- (E-chlorophenyl) -3,5-dichloro-1- (2,3,3-trichloroallyl) pyrrole-2-carbonitrile; 3-bromo-5-chloro-4- (E-chlorophenyl) -2-nitropyrrole; 5-bromo-4- [4- (2,2-dichloro-1,1-difluoroethoxy) phenyl] -3- (trifluoromethyl) pyrrole-2-carbonitrile; 2-chloro-3- (2-bromo-4-ethylthiophenyl) -5-nitro-4- (trifluoromethyl) pyrrole; 3- (3-bromo-4-acetylphenyl) -5- (trifluoromethyl) pyrrole-2-carbonitrile; 1-cyano-3- (3,4-dibromophenyl) -5-nitro-2- (trifluoromethyl) pyrrole; 3-bromo-l-methoxymethyl-4- (m-trifluoromethyl) -5- (trifluoromethyl) pyrrole-2-carbonitrile; 3- (E-chlorophenyl) -4-iodo-5-nitro-2- (trifluoromethyl) pyrrole;

II

11,91523 4- (E-bromophenyl) -1 -C (1-ethoxy) ethyl] -3,5-di- (trifluoromethyl) pyrrole-2-carbonitrile; 3- (3-bromo-4-methoxyphenyl) -5-nitro-2,4-di- (trifluoromethyl) pyrrole; 3- (E-chlorodifluoromethoxyphenyl) pyrrole-2,5-dicarbonitrile; 2- (E-isobutyrylaminophenyl) -5-nitropyrrole-2-carbonitrile; 3-bromo-4- (3,4-dimethoxyphenyl) pyrrole-2,5-dicarbonitrile; 4-chloro-3- (E-chlorophenyl) -1-isopropyloxycarbonylmethyl) -5-nitropyrrole-2-carbonitrile; 3- (o-bromophenyl) -4- (trifluoromethyl) pyrrole-2,5-dicarbonitrile; 1- (2-chloroethyl) -3- (3,4-dichlorophenyl) -4- (trifluoroethyl) pyrrole-2-carbonitrile; 4- (4-bromo-3-trifluoromethoxyphenyl) -3-chloropyrrole-2-carbonitrile; 3-bromo-4- (2,4-dichlorophenyl) -1-isopropyl-2-nitropyrrole; 4- (3-methoxy-4-cyanophenyl) -3- (trifluoromethyl) pyrrole-2-carbonitrile; 1- (3,4-dichlorobenzyl) -4- (2-methyl-4-iodophenyl) -2-nitro-3-trifluoromethylpyrrole; * 25 1-methyl-4- [3,5-di (trifluoromethyl) phenyl] pyrrole-2,3-dicarbonitrile; 4- (3,4-Dichlorophenyl) -2-nitropyrrole-3-carbonitrile; 4- (m-bromophenyl) -1-carbomethoxymethyl-5-chloropyrrole-2,3-dicarbonitrile; 5-Bromo-4- (2,6-dichloro-4-methanesulfinyl-phenyl-2-nitropyrrole-3-carbonitrile; 4- (E-chlorophenyl) -1- (2,2,2-trifluoroethyl) -5- (trifluoromethyl) ) pyrrole-2,3-dicarbonitrile, 4- (3,5-dichlorophenyl) -2-nitro-5- (trifluoromethyl) -35 pyrrole-3-carbonitrile, 2-chloro-4- (3-chloro-4-N -methylacetamidophenyl) pyrrole-3-carbonitrile 12 91 523 2-bromo-4- (3-bromo-4-n-propylphenyl) -3-nitropyrrole 2,5-dichloro-4- (3,5-dichloro-4-methylthiophenyl ) pyrrole-3-carbonitrile; 2,5-dibromo-1- (2,4-dibromophenoxymethyl) -3- (N-chloro-5-phenyl-4-nitropyrrole; 4- (3-bromo-4-cyanophenyl) -2 -Chloro-5- (trifluoromethyl) pyrrole-3-carbonitrile, 2-bromo-1-methyl-3-nitro-4- (α, N, N-trifluoro-ε-tolyl) pyrrole; (chlorophenyl) -1- (n-butyloxymethyl) -5-trifluoromethyl) pyrrole-3-carbonitrile; 4- (3,4-methyldioxyphenyl) -3-nitro-2- (trifluoromethyl) pyrrole; 4- (3-chloro-4-trifluoromethoxyphenyl) -2- (trifluoromethyl) pyrrole-3-carbonitrile; 2-bromo-3- (3 , 4-dichloro-phenyl) -l-ethylthiomethyl-4-nitro-5- (trifluoromethyl) pyrrole; 4 - / £ - (tetrafluoroethoxy) fenyyli7 ~ 2,5-di- (trifluoromethyl) pyrrole-3-carbonitrile.; 3- (3-bromo-4-acetoxyphenyl) -1- (3,4-dichlorophenoxymethyl) -4-nitro-2,5-di- (trifluoromethyl) pyrrole; 4- (E-bromophenyl) -1- [(2-methoxy) ethyl] pyrrole-2,3-dicarbonitrile; 4- (m-isopropionamidophenyl) -3-nitropyrrole-2-carbonitrile; 5-bromo-4- (2-chloro-4-methylthio) pyrrole-2,3-dicarbonitrile; 5-chloro-4- (£-chlorophenyl) -l-hydroxyethyl-3-nitro-pyrrole-2-carbonitrile; 4- (3,5-dibromo-4-cyanophenyl) -5- (trifluoromethyl) pyrrole-2,3-dicarbonitrile; 4- (4-chloro-2-methylphenyl) -1-isopropylthiomethyl-3-nitro-5- (trifluoromethyl) pyrrole-2-carbonitrile; 5-bromo-4- (3,4-dichlorophenyl) -1- (difluoromethyl) -3-pyrrole-3-carbonitrile; 2-chloro-3- (m-difluoromethoxyphenyl) -4-nitropyrrole; 13,91523 1- (2,4-dibromophenoxymethyl) -4- (m-chlorophenyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile; 3- (3-bromo-4-ethoxy) -4-nitro-2- (trifluoromethyl) pyrrole; 3- (2,4,6-trichlorophenyl) pyrrole-2,4-dicarbonitrile; 3- (4-bromo-3-chlorophenyl) -1- (difluoromethyl) -4-nitro-5-pyrrole-2-carbonitrile; 5-bromo-3- (p-chlorophenyl) -1- (isobutyryloxymethyl) pyrrole-3-carbonitrile; 3- (4-bromo-3-methylphenyl) -5-chloro-4-nitropyrrole-2-carbonitrile; 3- (2-naphthyl) -5- (trifluoromethyl) pyrrole-2,4-dicarbonitrile; 3- (3-cyano-4-methylphenyl) -1-methyl-4-nitro-5- (trifluoromethyl) pyrrole-2-carbonitrile; 2,3-dichloro-5- (3,4-dichlorophenyl) -4-nitropyrrole; 2- (3,5-dibromo-4-methoxyphenyl) -4,5-dichloropyrrole-3-carbonitrile; 2,3-dichloro-4-nitro-5- (2,4,6-trifluorophenyl) -4-nitropyrrole; 4,5-dibromo-2- (2,3,6-trifluoromethyl) -3-carbonitrile; 4,5-dichloro-2- (3,4-dichlorophenyl) -1- (ethoxymethyl) pyrrole-3-carbonitrile; 4,5-Dibromo-1-methyl-2- (CL-trifluoro-p-tolyl) -pyrrole-3-carbonitrile; 4,5-dichloro-2- (3,4-dichlorophenyl) -1-ethylpyrrole-3-carbonitrile; 2,3-dichloro-4-nitro-5- [E- (trifluoromethoxy) phenyl] pyrrole; 4,5-dichloro-2- [in- (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; and 4-bromo-5-chloro-2- (p-chlorophenyl) -1-methylpyrrole-3-carbonitrile; 14 91 523 5-chloro-2- (3,4-dichlorophenyl) -4-fluoropyrrole-3-carbonitrile; 2-bromo-5- (p-chlorophenyl) -1- (ethoxymethyl) -4-fluoro-pyrrole-3-carbonitrile; 5 3-Bromo-5- (E-chlorophenyl) -2-fluoro-4-nitropyrrole.

In the preparation of the compounds (I), α- [2,2-di (C 1-4 alkoxy) ethylamino] -β-cyanostyrene and α- [2,2-di (C 1-4 alkoxy) can be used as starting materials. ethylamino] -p-nitrostyrene compounds having the following structure):? - c = Chu 15 R - NH-CH 2 CH (C 1 -C 4 alkoxy) 2 wherein W is CN or NO 2; L is H, F, Cl or Br; M and R are each independently H, C 1-6 alkyl, C 1-3 alkyl-sulfonyl, cyano, F, Cl, Br, nitro, CF 3, OCF 3 or R 2 CO, and when in adjacent positions M and R may be taken together with carbon atoms, to which they are attached forms a ring in which MR represents the structure: and R 2 is C 1 -C 3 alkyl or C 1 -C 3 alkoxy.

The primary group of β- (substituted) styrene compounds has the above structural formula wherein W is CN; L is H, Cl or Br; M is H, F, Cl, Br or OCH 3; R is H, F, Cl, Br, CF 3, NO 2, OFF 3 or OCH 3; or when in adjacent positions M and R may be taken together with the carbon atoms to which they are attached to form a ring in which MR represents the structure: A second preferred group of β- (substituted) styrene compounds has the above structural formula wherein W is NO 2; L is H, Cl or Br, M is H, F, Cl, Br or OCH 3; R is H, F, Cl, Br, CF 3, NO 2, OCF 3 or OCH 3; or when in adjacent positions M and R may, together with the carbon atoms to which they are attached, form a ring in which MR represents the structure:

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

Some preferred dialkyl acetal compounds are (E) and (Z) (1) E-chloro-β-Ε (formylmethyl) amino] cinnamonitrile-diethyl acetal; (2) β - [(formylmethyl) amino] -3,4-dimethoxycinnamone triil-diethyl acetal; (3) (5S) -methyl-β- {2-cyano-1 - [(formylmethyl) amino] vinyl] benzoate-diethyl acetal; (4) (Z) -β - [(formylmethyl) amino] -1-naphthaleneacrylonitrile-diethyl acetal; (5) (Z) -β - [(formylmethyl) amino] -g-methylcinnamone-30-tridimethylacetal; (6) N- (formylmethyl) -g-methyl-α- (nitromethylene) -benzylamine-diethylacetal; (7) N- (formylmethyl) -3,4-dimethoxy-α- (nitromethylene) -benzylamine-diethylacetal; 16,91523 (8) N- (formylmethyl) -α- (nitromethylene) -2-naphthalenemethylamine diethyl acetal; (9) methyl g- {α - [(formylmethyl) amino] -β-nitrovinyl} benzoate g- (diethyl acetal); 5 (10) N-formylmethyl) -3,4-dimethoxy-α- (nitromethylene) benzylamine dimethyl acetal; (11) (E) - and (Z) -g-chloro-p - [(formylmethyl) amino] quinamonitrile dimethyl acetal; (12) β - [(formylmethyl) amino] -3,4-dimethoxycinnamonitrile dimethyl acetal; (13) 3,4-dichloro-p - [(formylmethyl) amino] cinnamonitrile diethyl acetal; and (14) g-trifluoromethyl-β - [(formylmethyl) amino] Kinna monitrile diethyl acetal.

Β-Cyanostyrenes, also called cinnamonitrile dialkyl acetals, can be prepared by reacting a substituted or unsubstituted benzoylacetonitrile with 2,2-di (C 1-4 alkoxy) ethylamine in the presence of an aromatic solvent to give the α-20. C 1-4 alkoxyethylamino (cyano-substituted) styrene, which can then be converted to 2- (substituted-phenyl) -pyrrole-3-carbonitrile by reacting said β-3-cyano- (substituted) styrene compound with trifluoroacetic acid. Chlorination of the cyanophenylpyrrole thus prepared with sodium hypochlorite or sulfuryl chloride in an inert solvent gives 4,5-dichloro-2- (substituted-phenyl) pyrrole-3-carbonitrile from the insecticide, acaricide, and nematicide. Conversion to the pyrrole intermediate can also be performed using concentrated HCl at a temperature between about 20-40 ° C. The reactions can be plotted as follows: I! 17 91523

Reaction Scheme 5 // ° (O \\ _ c ♦ H.NCH, CH <OC, H.)? A = / '^' ^ y ^ aromatic solvent 10 / γζη r * JL - - * 1 S ° -R6 15 CF3CO2h or HCl

_ / CN X CN

20 ΐΓχ ^ Κ "Na0C1 __ R so2cie \ _x

or Bre R

koccch3) 3

0- I

V

25 X

30 35 18 91 523 wherein A is hydrogen, C 1-4 alkyl optionally substituted with one C 1-4 alkoxy group, one C 1-4 alkylthio group, one to three halogen groups, or phenyl optionally substituted with one or more two C 1-5 alkyl, C 1-4 alkoxy, or halogen groups; C3-4 alkenyl optionally substituted with three halogen groups; or C3-4 alkynyl; X is Cl or Br; R 6 is C 1-4 alkyl and L, R and M are as described above.

Certain novel arylpyrrole compounds of formula I wherein A is hydrogen; W is CN and X, Y, L, M and R

are as described above can be prepared by administering N-formyl-DL-phenylglycine or substituted N-formylphenylglycine represented by Structural Formula VIII:

15 L

y — ch <viii) NHCH = 0

R

Wherein L is H, F, Cl or Br; R and M are each independently H, C 1-4 alkyl, C 1-3 alkoxy, C 1-4 alkylsulfonyl, cyano, F, Cl, Br, nitro, CF 3, OCF 3 or R 2 CO, and when adjacent positions M and R may together form With the 25 carbon atoms to which they are attached, react with a ring in which MR represents the structure: and R 2 is C 1-3 alkyl or C 1-4 alkoxy with at least an equivalent amount of 2-chloroacrylonitrile and two to three. equivalent of acetic anhydride. The reaction is carried out at an elevated temperature, preferably at about 70-100 ° C.

The reaction can be represented as follows: 19,91523

L

H I COgH h

Ν / ΓΓλ X. RcgO

/ Λ \\ - CH + CH2 = C + CN --- 5> S’NHCH = 0

R

CN

ζί in _ (VIII) et al

10 R

Conversion of 2-phenylpyrrole-3-carbonitrile or 2- (substituted phenyl) pyrrole-3-carbonitrile thus prepared to the corresponding formula 4-halogen-15-, 5-halogen or 4,5-dihalo-2- (substituted phenyl) ) to pyrrole-3-carbonitrile is readily accomplished by reacting the aforementioned 2-phenylpyrrole-3-carbonitrile or 2- (substituted phenyl) pyrrole-3-carbonitrile with at least about 1 or 2 equivalents of sulfuryl halide, bromine, or chlorine, in the presence of a solvent such as dioxane, THF, acetic acid or a chlorinated hydrocarbon solvent. To prepare monohalopyrrole-3-carbonitrile, it is necessary to use about 1 equivalent of halogenating agent; while the preparation of dihalogen / pyrrole-3-carbonitrile requires 2-3 equivalents of said halogenating agent. When sulfuryl chloride or sulfuryl bromide is used, the reaction is generally carried out at a temperature below about 40 ° C and preferably at about 0-30 ° C, but when using the bromine element, the reaction is usually carried out at about 30-40 ° C. Other effective halogenating agents that can be used in these reactions include sodium hypochlorite, t-butyl hypochlorite, N-bromosuccinimide, N-iodosuccinimide, and the like. The reaction can be described as follows:

, CN X CN

7r \ // I \> <C Bpi »cla> soa <x> 2, v H

H X _HORc * H NT / TaC

10 N- r \ = / \

R

(II) The carbonitrile compounds of formula II of this invention can also be prepared by reacting substituted or unsubstituted benzoylacetonitrile with 2,2-di (C 1-4 alkoxy) ethylamine in the presence of an aromatic solvent to form α- (2,2-di ( C 1-4 alkoxy) ethylamino) -β-cyano- (substituted) styrene, which is then converted to 2- (substituted-phenyl) -pyrrole-3-carbonitrile of formula II by giving said β-3-cyano- (substituted) -styrene to react with trifluoroacetic acid or concentrated HCl at a temperature between about 20-40 ° C.

The reaction can be described graphically as follows:, · • · <21 91523

reaction scheme

L

5 Π ') ^ Λ-ο // + h2nch2ch <oc2h5> 2

/ 'CZIJ \ —CN

R \ / \ / aromatic γ solvent 10 R [_ H 6 15 CF3CO2H or HCl 't

CN

OJ Jk »20 j

R

Wherein R 9 is C 1-6 alkyl and L, R and M are as described above. Likewise, according to the present invention, the 3-nitro-2-phenylpyrrole and 3-nitro-2- (substituted) phenylpyrrole compounds of formula II can be prepared by reacting% nitroacetophenone or substituted o-nitroacetophenone with 2.2- with di (C 1-4 alkoxy) ethylamine. The reaction is usually carried out in the presence of an inert organic solvent, preferably an aromatic solvent, at elevated temperature to give O 6 - (2,2-di (C 1-4 alkoxy) ethylamino) -β-nitrostyrene 35 or substituted C 1- (2,2-di (C 1-4 alkoxy) ethylamino) 22,91523 nitrostyrene which is converted to 3-nitro-2-phenylpyrrole of formula II or 3-nitro-2- (substituted) -phenylpyrrole by treatment with an inorganic acid such as hydrochloric acid or hydrobromic acid.

Reaction of the nitrophenylpyrrole thus prepared with sodium hydrochloride in the presence of an inert organic solvent at reduced temperature gives 2,3-dichloro-4-nitro-5-phenyl or 5- (substituted) -phenylpyrrole of formula II.

10 The above reactions can be described graphically as follows: vk s c-ch2no2 + H2NCH2CH <0C2H5) 2 _ 15

R

L

«_

/ <= / XN — CH2CH <0C2H5> 2 R H

20

HCl or CF3CO2H

no2 25 / “^ νΠ H \ —X C1 \ NO2

NaOCl Π

- * C1 H

R

CII) 91 523 23

In addition to several methods described in the literature for the preparation of substituted and unsubstituted benzoylacetonitriles, it has surprisingly been found that these compounds can also be prepared by reacting an appropriately substituted benzoyl halide with an alkali metal hydride and an alkylated butylate benzoyl) syaanoasetaattia. These reactions can be plotted as follows: LO 1 H ^ c-oc <ch3> 3 SAv <£> y — C-Cl * NaH ♦ ch2 _ ^ (q, y — C0-C-C0-0C <CH3 ) 3

R CM R _ CN

The cyanoacetate ester thus formed can then be converted to substituted or unsubstituted benzoylacetonitrile by heating the compound in toluene with E-toluenesulfonic acid. The reaction can be described graphically as follows: -C0-C-C0-0C <CH3> 3 - 25 ίκ toluene 1 »

Examples of t-butyl (benzyl and substituted benzoyl) aceto-nitriles used in the above strokes are shown in the tables below.

24,91523 t-butyl (benzyl and substituted benzyl) cyanoacetates 5

L

n io (p, \\ - C0-C-C0-0C (CH3) 3)

^ CN

15 Xj Jä r SP ° c H 3 “Cl 4-Cl 91-94 HH 4-OCF3 81-84 HH 4-Br 113-115 HH 4-CF3 146-147 20 HH 4-F 98-100 HH 4-CN 127-128 HH 4-CF 3 CH 2 O 136-139 HH 4-CH 3 SO 2 127-129 H 3 -F 4-F 91-94; 25 H H 4-CH 3 S 117-119 f5 H H 4-CHF 2 CF 2 92-94 3-Cl 5 -Cl 4-CH 3 O- 25 91523

Benzoylacetonitriles 5 L 0 M__ ^ 7 ^ c-checn

R

15 L M R SP ° C

HH 4-C1 128 f 5-129.5 H 3-C1 4-Cl 105-107 HH 2-C 153-55 HH 4-OCF3 79-81 20 HH 4_CF3 44-45 H 2-C1 4-C1 66- 67 HH 3-C1 80-83 HH 4-CN 126-128 HH 4-F 78-80 25 HH 4-SO2 CH3 129-132 H 3-F 4-F 74-75 HH 3-CF3 58-60 HH 4- CH3 103.5-106 HH 4 -NO 119-124 30 ^ 3-Cl5-C1-4-OCH3 --- 26 91523 The preparation of N-substituted arylpyrroles of the formula I can be carried out by administering a suitably substituted arylpyrrole of the formula I in which A is hydrogen and L, M, R, W, X and Y are as described above, react with a suitable alkylating agent and a suitable base. Examples are brominated hydroxy-C 1-4 alkyl and potassium t-butylate. In this reaction, arylpyrrole having the same substituents as in the starting material is obtained, but in addition it has hydroxy-C 1-4 alkyl as a substituent on nitrogen. In a similar reaction, the brominated hydroxy-C 1-4 alkyl is replaced by cyanogen bromide to give an arylpyrrole of formula I having a carbonitrile substituent on the nitrogen. The reactions can be described as follows: 15 u U l tr 1) Br Cx-C4 alcohol + K + 0-t-Bu ao 'or K 2) CNBr

'* & · J

Wherein L, M, R, W, X and Y are as defined above for formula I and A is 1) C 1-4 alcohol or 2) CN.

2-Phenylpyrrole-3,4-dicarbonitrile, 2-bromo-5-phenylpyrrole-3,4-dicarbonitrile and their substituted phenyl derivatives can be obtained by reacting fumaronitrile with bromine in the presence of chlorinated carbon such as chloroform. at elevated temperature to give bromifumaronitrile.

The bromofumaronitrile thus formed is then reacted with N- (trimethylsilyl) methyl-5-methyl-benzene-5-thioimidate or a substituted derivative thereof in the presence of hexamethylphosphoramide at elevated temperature to give 2-phenylpyrrole-3,4-dicarbonitrile. Bromination of the 3,4-dicarbonitrile thus prepared gives 2-bromo-5-phenylpyrrole-3,4-10 dicarbonitrile, or a substituted phenyl derivative thereof, if a substituted N- (trimethylsilyl) methyl-5-methyl- benzene-thioimidate. The reaction can be described graphically as follows:

CN CN

_ / BiycHcyA _ / <-HBr> ”NC Br ♦

NC CN

2 0 Λ "· \\ / HHPfl / 3 eq. H8o ^ 8v l

- Tns ^ X / = Y

NH \\ JT <-TNS, “HBr, -CH 2 SH) W

R

Bre / CHCla

NC CN

\

The examples set forth below for purposes of illustration utilize the formulas described above and provide methods for preparing other compounds of the invention not specifically described herein.

The arylpyrroles of this invention are effective in controlling insects, mites and nematodes.

These compounds are also effective in protecting growing or harvested cereals from attack by the aforementioned pests.

Generally from about 10 ppm to about 10,000 ppm and preferably from 100 to about 5000 ppm of an arylpyrrole of formula I, including all arylpyrrole isomers of formulas II, III, IV, V, VI and VII, dispersed in water or other inexpensive liquid carrier, is effective when applied to plants, cereals or soil where said cereals grow to protect said cereals from insect, mite and / or nematode attack. These compounds are also useful for protecting lawns from attack by pests such as larvae, bedbugs and the like.

The arylpyrroles of formula I of this invention are also effective in controlling insects, nematodes and mites, when applied to the plant press and / or the soil or water in which said plants grow, in an amount sufficient to provide from about 0.125 kg / ha to about 4 .0 kg / ha. Obviously, higher application rates of the arylpyrroles of formula I can be used to protect cereals from insect, nematode and mite infestation, although higher application rates are generally unnecessary and uneconomical.

While the arylpyrroles of this invention are effective in controlling insects, nematodes and mites when used alone, they can be used in combination with other biological chemicals, including other insecticides, nematodes and mite poisons.

For example, the arylpyrroles of this invention can be used effectively in combination or in combination with phosphates, carbamates, pyrethroids, formamidines, chlorinated hydrocarbons, halobenzoyl ureas, and the like.

29,91523 2-Aryl-3-cyano-4,5-dihalopyrroles prepared from the β-cyano-styrene compounds of this invention are effective in controlling insects, mites and nematodes. These compounds are also effective in protecting growing or harvested cereals from attack by the aforementioned pests.

In general, in practice, about 10 ppm to 10,000 ppm and preferably 100 to 5,000 ppm of halogenated arylpyrrole, dispersed in water or other inexpensive liquid carrier, is effective when applied to plants, cereals or the soil where said cereals grow to protect said cereals from insects, mites and / or nematode attack.

The aforementioned halogenated arylpyrroles are also effective in controlling insects, nematodes and mites when applied to the press of plants and / or to the soil or water where said plants grow. These halogenated arylpyrrole compounds are usually applied in sufficient amounts to provide from about 0.125 kg / ha to about 4.0 kg / ha of active ingredient. Obviously, higher application rates of said halogenated arylpyrroles can be used to protect cereals from insect, nematode and mite infestation, although higher application rates are generally unnecessary and uneconomical.

The aforementioned arylpyrroles can be preferably formulated as dry compressed granules, flowable mixtures, granular combinations, wettable powders, emulsifiable concentrates, dusts, dust concentrates, foliar or protective and similar preparations, all of which are suitable for spreading. . Such formulations include the compounds of the invention in admixture with inert, pharmacologically acceptable solid or liquid diluents.

30 91523

For example, wettable powders, dusts and dust concentrate blend forms of the invention can be prepared by co-milling about 3-20% by weight of an arylpyrrole of formula I and about 3-20% by weight of a solid anionic surfactant. One suitable anionic surfactant is di-octyl ester of sodium sulfosuccinic acid, especially the Aerosol OTB ® surfactant marketed by the American Cyanamid Company. Such blend forms also use from about 60% to about 94% by weight of an inert solid diluent such as montmorillonite, attapulite, chalk, talc, kaolin, diatomaceous earth, limestone, silicates, or the like.

Compressed granules which are particularly useful for application to soil or water can be prepared by grinding with approximately equal proportions, usually about 3 to 20 parts of arylpyrrole and a solid surfactant, with about 60 to 95 parts of gypsum.

The mixture is then compressed into small granular particles, about 24/48 mesh or larger in size.

Other suitable solid surfactants useful in these blend forms include not only the anionic dioctyl ester of sodium sulfosuccinic acid but also the nonionic block copolymers of ethylene oxide and propylene oxide. Such segment-blended polymers are marketed by BASF Wyandotte Corporation as Pluronic 10R8®, 17R8®, 25R8®, F38®, F68®, F77® or F87® and are particularly effective in making compressed granules.

In addition to the powders and concentrate-30 blend forms described above, wettable powders and fluids can be used because they can be dispersed in water. Primarily, such fluids are applied with aqueous combinations which are sprayed on the press of the plants to be protected. These rye-35 spawning agents can also be applied to the breeding medium, nutrient medium or growth site of the insects and mites to be controlled.

31 91523

When solid blends of arylpyrroles are to be used in treatments with other pesticides, the blends may be applied as a mixture of ingredients or may be applied sequentially.

Likewise, liquid mixtures of arylpyrrole in combination with other pesticides can be mixed in a container or applied separately, sequentially, as liquid syringes. Liquid injectable formulations of the compounds of the invention 10 should contain from about 0.001 to 0.1% by weight of active arylpyrrole.

The following examples are provided for the purpose of illustrating this invention.

Example 1 2-Phenylpyrrole-3-carbonitrile

CN

COgH Cl / = \ / I flc20 /) - CH + CH2 = C-CN-► \ 20 '-' \ hCH = 0 [j Λ

The following method is similar to that described in JOC, 43, 4273-6 (1978). The magnetically stirred mixture of 30.00 g of N-formylphenylglycine is heated at 90 ° C for 1 1/2 hours. The bright yellow reaction solution is evaporated to dryness in vacuo to give 42.5 g of an oily brown-orange semi-solid. The material, which has been partially purified by chromatography on silica gel, shows a mixture of 73% 2-phenylpyrrole-3-carbonitrile and 27% 2-phenyl-3-cyano-5-methylpyrrole on the basis of pro-30 NMR spectra. Recrystallization once from chloroform and twice from 1,2-dichloroethane gives 1.69 g of an off-white solid which is shown by proton NMR to be 96% 2-phenylpyrrole-3-carbonitrile, mp 148-152 ° C.

> · · 32 91525

Microanalysis (mp 168.19):

Calculated: C 78.55, H 4.79, N 16.66%

Found: C 78.52, H 4.73, N 16.54%

Example 2 4,5-Dichloro-2-phenylpyrrole-3-carbonitrile and 5-chloro-2-phenylpyrrole-3-carbonitrile

CN CN

CN

Cl I

10 2eq SO 2 Cl + ^ A \, _ „ΑΆ / = \ CHoClp * A C1 NV \ HY \ /) 15 In a magnetically stirred solution cooled with ice water containing 2.00 g (11.9 mmol) of 2-phenyl-3- cyanopyrrole in 80 mL of methylene chloride is added dropwise via syringe over 5 minutes to 1-90 mL (3.19 g, 23.6 mmol) of sulfuryl chloride. During the addition, the heat-20 state is maintained between 5-10 ° C. Stirring is continued at 5-10 ° C for 90 minutes. The reaction mixture is filtered under vacuum to remove the precipitated solid (1.28 g) which is identified as 5-chloro-2-phenylpyrrole-3-carbonitrile, mp 192.5-105 ° C. The filtrate is diluted with 400 ml of ethyl acetate, washed twice with 200 ml of water, dried (sodium sulfate), treated with charcoal, filtered, and then evaporated to dryness in vacuo to give (after slurrying the residue with hexane), 60 g (yield 21.3%) of nei-30 dirty-purple solid. This solid is recrystallized from 5 ml of hot acetone to give 0.32 g (9% yield) of 4,5-dichloro-2-phenyl-pyrrole-3-carbonitrile as an orange-brown solid, mp 254-255 ° C.

33 91523

Max (Mull, Nujoi): 3165 (brs), 3120 (s), 2245 (s), 1570 (m), 1513 (m), 1440 (s), 1252 (111), 1069 (m), 996 (m ), 920 (m), 768 (s), 698 (s), 665 (s) cm-1.

1 H-NMR (DMSO): 57.73 (d, J = 6.6Hz, 1.97H, two phen-prot. At 5 C-2.6), 57.52 (t, J = 7.3Hz , 2.04H, 2 phenyl-proton at C-3.5), 57.44 (t, J = 7.3Hz, 1.02H, 2-phenyl-proton at C-4).

C-NMR (DMSO):% 137.51 (C-2 pyrrole carbon), >> 129.25 (C-4 phenyl carbon), £ 129.04 (C-3.5 phenyl carbons), 10 £ 128.37 (Cl phenyl carbon), £ 125.88 (C-2.6 phenyl carbons), £ 114.32 (either C-5 pyrrole or nitrile carbon), £ 114.14 (either C -5 pyrrole tax nitrile carbon), £ 110.72 (C-4 pyrrole carbon), £ 89.78 (C-3 pyrrole carbon). Microanalysis (mp 237.09): Calculated: C, 55.72%; H, 2.55%; N, 11.82%; Cl, 29.91%

Found: C, 55.78%; H, 2.59%; N, 11.12%; Cl, 29.74%

Example 3 p-Chloro- (5- (E-formylmethyl) amino / cinnamonitrile, diethyl acetal 20 toluene)

cMqXc »· c, -w ^ iA

· - 25 A magnetically stirred solution of 250.00 g (1-39 moles) of E-chlorobenzoylacetonitrile, 203 ml (185.95 g, 1.39 moles) of 2,2-diethoxyethylamine and 1300 ml of dried toluene is heated to reflux. hours. Water is collected in a Dean-Stark trap (23.8 ml, 95.2% of theory). A hot cloudy dark brown solution * with a large amount of insoluble solids is filtered through a diatomaceous earth filter. After diluting with 200 ml of ethyl acetate, the solution is filtered through a 7 cm x 13.5 cm silica gel column. The filtrate is concentrated in vacuo to give 354.38 g (yield 34,91523 86.4% crude product) of a clear dark oil which slowly converts to a solid. This solid is recrystallized from hot cyclohexane to give 324.26 g (79.1% yield) of a waxy orange solid. NMR of this product shows a mixture of p-chloro- [3 - [(formylmethyl) amino] -cinnamitrile, 78% isomer of diethyl acetal and 23% of (E) -isomer, mp 60-72 ° C. The following analytical values are the values of another sample 10 prepared in the same manner.

Max (Mull. Nunoli: 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): $ 7.47 (d, J = 8.6Hz, 2.12H, two aromatic protons),% 7.37 (d, J = 8.6Hz, 2.12H, two aromatic protons) ), £ 5.10 (E) & 4.86 (Z) / br t, 1.25, one NH proton, -6 4.69 (Z) & 4.60 (E) / t, J = 5, 1Hz, 1.05H, one methine proton on acetal-carbon ?, £ 4.07 (E) & o 20 4.05 (Z),? _, 0.83H, enamine proton7, £ 3.71 (E ) & h 3.68 (Z), / q, J = 7.1 Hz, 2.22H, two methylene protons from the other two ethoxy groups /, £ 3.56 (Z) & r ^ 3.53 (E) / q, J = 7.1 Hz, 2.22H, two methylene protons from the other two ethoxy groups /, <3.18 (t, J = 5.1 Hz, 1.77H, two methylene protons from the ethylene acetal group), h 1, 20 (t, J = 7.1 Hz, 4.90H, six methyl protons from two ethoxy groups).

C-NMR (chloroform): ε> 161.21 (ε-enamine-carbon), $ 136.29 (Z) & 134.60 (E) / {either Cl or C-4 in the phenyl ring ?, 30 134, 08 (Z) & $ 132.30 (E) j {either Cl or C-4 in the phenyl ring7 / ^ 129.34 (Z) & <$ 129.89 (E) / either C-2.6 or In the C-3,5 phenyl ring.7, 128.94 (Z) & £ 128.63 (E) / in either the C-2.6 or C-3,5 phenyl ring_7, £ 21.19 (Z) & £ 119.50 (E) / nitrile carbon /, <$ 99.43 (Z) & £ 100.63 (E) 35 Zj /? - enamine carbon7, £ 61.88 (Z) & £ -63.25 ( E) / in methine-carbon acetate /, £ 62.64 (Z) & 63.03 (E) / methylene-carbon of ethoxy groups7, 46.32 (Z) & ^ 47.33 (E) Ethylamine methylene carbon /, 15.26 (methyl carbons of ethoxy groups).

Microanalysis (mp 294.78): δ Calculated: C / 61.11%; H, 6.50%; N, 9.51% Cl, 12.03%.

Found: C, 61.25%; H, 6.25%; N, 9.34%; Cl, 12.35%.

Example 4 2- (p-Chlorophenyl) pyrrole-3-carbonitrile

.. / CN CN

10 C I

Cl_C // λ λ + CF3C ° 2H - ”C \ / = \ n — f ha— / N0—. To a solution of 108 ml of trifluoroacetic acid stirred at 23 ° C is added 54.00 g (0.183 moles) of solid ε-chloro-β - [( formylmethyl) amino-cinnamonitrile, diethyl acetal over 45 minutes. This addition caused an exothermic reaction up to 38 ° C and 32 minutes after the addition a solid began to precipitate. After stirring for 30 minutes at room temperature, the reaction mixture is filtered under vacuum and the collected solid is washed first with trifluoroacetic acid, secondly with ethyl acetate-hexane and finally with hexane. The yield is 16.83 g (45.4%) of an off-white solid, mp 165-166 ° C. The following analytical values are those given for a sample prepared in the same way. ljax (Mull, Nujol): 3275 (br s), 2225 (s), 1502 (s), 30 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 br s, 0.99H, one pyrrole NH proton), δ 7.82 (d, J = 8.9Hz, 2.46H, two aromatic phenyl protons), $ 7.51 (d, J = 8.9Hz, 2.46Hz, two to 35 aromatic phenyl protons), <7.02 (t, J = 2.6Hz, .. 1.01H, one pyrrole- proton in C-5), δ 6.58 (t, J = 2.6Hz, 0.77H, one pyrrole proton in C-4).

36 91523 C-NMR (acetone): ε> 137.73 (pyrrole C-2), δ 134.42 (ε-chlorophenyl in C-4), ν 129.93 (methine carbons in phenyl ring C -3.5), £ 129.93 (methine carbons in C-3.5 of the phenyl ring), 128.07 (methine carbons in C-2.6 of the phenyl ring), 121 , 21 (pyrrole in C-5), ^ 117.93 (nitrile carbon), b 113.78 (pyrrole carbon in C-4),% 90.86 (pyrrole carbon in C-3) .

Microanalysis (mp 202.64):

Calculated: C, 65.19%; H, 3.48%; N, 13.83%; Cl, 17.50% Found: C, 64.18%; H, 3.52%; N, 13.63%; Cl, 17.74% Using the above procedure or substituting concentrated hydrochloric acid for trifluoroacetic acid, the following compounds are obtained:

CN

15 _ / M

\> \, - V R

: Xjr 20 M j, ay or R mp ° C Acid used

4-Cl 165-166 conc. HCl, CF 3 COOH

3.4- di-Cl 216-221 CF3COOH

2- Cl 156-157 CF3COOH

4-OCF3 143-145 CF3COOH

25 4-CF 3 179-180 CF 3 COOH

2.4- di-Cl 197-199 CF3COOH

3- Cl 150-156 CF 3 COOH

4- CN 210-212 CF3COOH

4-F 167-170 cone. HC1

30 4-SO 2 CH 3 221-221.5 CF 3 COOH

3.4- di-F 173-175.5 CF 3 COOH

3- CF3 166-168 CF3COOH

4- COOCH3 155.5-158 CF3COOH

4-CH-117-137 CF 3 COOH

35 4-NO 2 174-177 CF 3 COOH

37 9 1 5 2 3

Example 5 4,5-Dichloro-2- (p-chlorophenyl) pyrrole-3-carbonitrile CN rw

5 Cl CN

jj ^ 2.2 eq. SO2Cl2 Jj ^ HORc * AnA / = \ H C1 C1 H C1 10

To a mechanically stirred solution of 16.83 g (83.1 germ) of 2- (p-chlorophenyl) pyrrole-3-carbonitrile in 450 ml of glacial acetic acid at 36 ° C is added dropwise over 18 minutes 14.7 ml (24 , 70 g, 183.0 mmol) of sulfuryl chloride. The addition causes the temperature to rise exothermically to 39 ° C and after a further 16 minutes, the reaction mixture is filtered under vacuum. The collected solids are washed first with acetic acid and then with water. After recrystallization from hot ethyl acetate, this solid melts at 259-261 ° C.

Other samples of this product were prepared by similar methods and the analytical values of one such product are shown below.

Max (Mull, Nujol): 3170 (br s), 3100 (m), 2225 (s),; 1508 (m), 1097 (m), 825 (s), 717 (m), 660 (m) cm-1.

1 H-NMR (DMSO): dl.12 (d, J = 8.6Hz, 2.0OH, two aromatic protons), b 7.56 (d, J = 8.6Hz, 2.0OH, two aromatic protons).

C-NMR (DMSO): δ 136.01 (pyrrole C-2 carbon), δ 133.92 δ (p-chlorophenyl C-4 carbon), δ 129.09 (p-chlorophenyl C-3.5 carbons), Λ 127.41 (p-chlorophenyl C-4 carbon), 127.11 (p-chlorophenyl Cl carbon), b> 114.49 (nitrile carbon), b 114.10 (pyrrole C-5 carbon), S 110, 92 (pyrrole C-4 carbon), b 90.09 (pyrrole C-3 carbon).

35 Microanalysis (mp 271.64): 38,91523

Calculated: C, 48.65%, H, 1.86%; N, 10.32%; Cl, 39.17%

Found: C, 49.22%; H, 2.12%; N, 9.85%; Cl, 39.03%

Example 6 4,5-Dibromo-2 - (, .beta.-trifluoro-p-tolyl) -5-pyrrole-3-carbonitrile

Γ Br \ / N

(Λ + Br2 - * JT \ _ 10 N \ / - \ \ _ΓΓ H CF3 H \ // 3

To a stirred mixture of 0.8 g of 2- (trifluoro-ε-tolyl) -pyrrole-3-carbonitrile in 70 ml of chloroform is added 2 ml of bromine. Upon stirring overnight, a white solid precipitates which is collected by filtration. Thin chromatography (1: 1 ethyl acetate-hexane) shows a single component; mp> 230 ° C.

Analysis for C- ^ 2H5Br2F3 ^ 2:

Calculated: C 35.55, H 1.27, N 7.11, Br 40.61%

Found: C 36.40, H 1.08, N 6.99, Br 40.55%

Following the procedures of Examples 5 and 6, but substituting appropriately substituted phenylpyrrole-3-carbonitrile for 2- (N, N'-trifluoro-E-tolyl) -25 pyrrole-3-carbonitrile, the following compounds are obtained.

39 91523

X CN

s Jr \ ϋ / - \ m

iU

10 L M R X Y s p ° C

HH 4 -NO2 Br Br 274-277 HH 4-F Cl Cl> 220 HH 4-F Br Br> 220 HH 4-SO2CH3 Cl Cl> 230 15 H 3-F 4-F Cl Cl> 230 H 3-F 4 -F Br Br> 220 2-Cl 3-Cl 4-Cl Cl Cl 2-Br 3-Br 4-Br Br Br HH 4-OCF3 Cl Cl 222-225 20 HH 4-OCF3 Br Br 231-232

H H 4-OCF3 Cl H

HH 4-CN Br Br> 230 HH 4-CN Cl Cl> 240 HH 4-SO 2 CH 3 Br Br> 230 - 25 HH 4-NO 2 Cl Cl 246-249 H 3 — Cl 4 — Cl Br Br> 260 HH 3-CF3 Cl Cl> 230 HH 4-COCH3 Cl Cl 251-254 H 2,3-CH = CH- Cl Cl 244-247 30 HH 4-CH3 Cl Cl 215-217 H 2-Cl 4-Cl Br Br> 230 40 91523

L M R X Y s p ° C

H H 3-Cl Cl Cl> 230 H 2-Cl 4-C1 Cl Cl> 230 5 H H 4-Cl Br Br 273-274 H H 2-C1 Br Br> 230 H H 4-CF 3 Cl Cl> 230 H H. 4-Br Cl Cl> 235 HH 2-Cl Cl Cl> 230 10 h 3-Cl 4-Cl Cl Cl> 235 HHH Cl Cl 254-255 HH 4-Cl Cl Cl 255-257 HH 4-CF3 Br Br> 230 HH 4-Cl Cl Br 262-263 (dec.) 15 HH 4-Cl Br Cl 250-258 (dec.) H 3-C1 5-Cl Cl Cl> 230 H 3-Cl 4-Cl Cl Br> 230 2 -C 14 -Cl 5 -F Cl Cl 207-210 20 Example 7 3-Nitro-2-phenylpyrrole no 2 CCH 2 NO 2 HgNCH 2 CH <OEt> 2 -► C = CH-NO 2 -? -Nitroacetophenone (5.7 g, 0 .3345 moles) is dissolved in 100 ml of toluene and 4.6 g (0.0345 moles) of aminoacetaldehyde diethyl acetal are added. The reagents are placed in a 250 ml RB flask fitted with a Dean-Stark trap. The trap is filled with a 4A molecular sieve and the mixture is heated at reflux for 18 hours. The toluene is removed in vacuo to give 8.36 g of oC- (2,2-diethoxyethyl-35-amino) -β-nitrostyrene as a brown oil. To this oil is added 50 ml of concentrated HCl. When the bottle is swirled, the oil forms a yellow suspension. After 10 minutes, the solid is filtered off to give 2.48 g of a yellow solid. Recrystallization from ether / ethyl acetate / hexane gives the product in two fractions, 2.08 g, mp 190-192 ° C; (31%).

1485 cm -1 (NO 2), 1 H-NMR (CDCl 3 / DMSO) 56.73 (111.211), 7.46 (m, 5H).

Example 8 2,3-Dichloro-4-nitro-5-phenylpyrrole NO 2 Cl NO 2 / TA + NaOCl → J

A mixture of 3-nitro-2-phenylpyrrole (1.56 g, 0.0083 mol) in 60 ml of dioxane is cooled by dropwise addition of 25.9 g (0.0182 mol) of technical grade sodium hypochlorite in an ice bath. After stirring for 45 minutes, the mixture is acidified with concentrated HCl. Add water and Et 2 O. The layers are separated and the supernatant is washed with H 2 O, dried over anhydrous MgSO 4 and evaporated to dryness in vacuo to give 2.21 g of a yellow solid. Purification by chromatography on silica gel, eluting with increasing proportions of ethyl acetate / hexane, gives, after evaporation to dryness, 0.77 g of a yellow solid (36%), m.p. 190-190.5 ° C.

Analysis for the compound:

Calculated: C 46.72, H 2.35, N 10.90% 35 Found: C 46.96, H 2.86, N 10.02% • · 42 91523

Following the procedures of Examples 7 and 8, but using appropriately substituted c 1-4 nitroacetophenone and 2,2-di (C 1-4 alkoxy) ethylamine, substituted O (7 (2,2-di (C 1-6 alkoxy)) is obtained. ethylamino) - / 3-nitrostyrene, which is then converted to 3-nitro-2- (substituted) phenylpyrrole by treatment with NCl, HBr or CF 2 CCl 4 Ht. The reaction of the substituted phenylpyrrole thus formed with sodium hypochlorite in dioxane gives chlorine. while substituted phenyl-10-pyrrole reacts with bromine in chloroform to give bromine analogs.

x no2 15 H ^ 4- Π

x R

L M R X Y sb ° C

20 HHH Cl Cl 190-190 ^ 5 H 4 — Cl H Cl Cl 214-215 H 4-Cl H Br Br 203-204 (dec.) HHH Br Br 148.5-149 3-C1 4 — Cl C Cl Cl 219-220 (dec.) 25 H 4-Br H Cl Cl 222-223 (dec.) HH 4_CF3 Cl C1 166-168

Example 9 4,5-Dichloro-2- (3,4-dichlorophenyl) -1-methylpyrrole-3-carbonitrile

C1v / N Cl CN

_ / C1 C1 ci S \ yT \) _ ci ♦ tteI + K ° C <CH3> 3 -► Cl / 35 \ - / Me \ _ / Cl 43 91523 in a 100 ml flask of 2 g of 4,5-dichloro A clear brown solution of -2- (3,4-dichlorophenyl) -pyrrole-3-carbonitrile is formed in 60 ml of dry THF. 1 equivalent of KOtBu is added with stirring to give a clear solution after a few minutes. Using a syringe, add 1 equivalent of methyl iodide and heat the solution to boiling for 4 hours. It is then stirred at room temperature overnight. The next day, 50 mL of CH 2 Cl 2 is added and the mixture is extracted with 4 x 50 mL of 10 CHCl 3. The organic phases are combined, dried over MgSO 4 and evaporated to dryness. The white solid formed is purified by flash chromatography on silica gel using a 50/50 mixture of ethyl acetate / hexane as eluent. This gives 1.80 g of a white solid.

Yield = 86%

Mp = 154-156 ° C.

Following the above procedure but substituting the appropriately substituted phenylpyrrole-3-carbonitrile or 3-nitro-2- (3,4-dichlorophenyl) -pyrro-20β-3-carbonitrile for 3-nitro-2- (substituted) - phenylpyrrole, the compounds shown below are obtained.

44 91 523

X CN

5 J / ~ \ Y X \, - v Π TXl ίο N-

A L M R X Y s p ° C

CH3 H H 4-Cl Cl Cl 152-153 C_HcOCH_ H 3-Cl 4-Cl Cl Cl 128-130 2 D 2 C-H ,. H 3 -Cl 4 -Cl Cl Cl 137-138 15 15 CH3 H 3 — Cl 4-Cl Cl Cl 154-156 CH3 H H 4 “CF3 Br Br 145-146 C H -CH0 H H 4-CF_ Br Br 145-147

O D 2 J

C ^ Hc-CH_ H 3-Cl 4-Cl Cl Cl 95-96 bo 2 CH2 = CH-CH2 H 3 — Cl 4-Cl Cl Cl 69-70 20 CH2 = C-CH2 H 3 — Cl 4-Cl Cl Cl

Cl CH = C-CH2 H 3-Cl 4-Cl Cl Cl 147-148 CH3SCH2 H 3-Cl 4-Cl Cl Cl C (CH_) HH 4 — CF Cl Cl 25 JJ 3 CH3 HH 4_CF3 Cl C1 99-100 CH SC H, H 3 -Cl 4-Cl Cl Cl 74-75 J 2 0 0 C2H5-OC-CH2 H 3-Cl 4-Cl Cl Cl 118-120 CH —OCH_ HH 4-CF ^ Cl Cl 99-100 2 q 2 0 2 3 CH3 HH 4-OCH3 Br Br 112-115 CH3 HH 4-Cl Br Br 197-201 CH OCH HH 4-0CF_ Cl Cl 46-47 2 0 2 3 CH3 HH 4-OCF3 Cl Cl 72-73

CcH -CH_ H H 4-OCF. Cl Cl oil 35 5 5 2 3 C2H5OCH2 H H 4-Cl Cl Cl 45 91523

A LH B - - §LB — Q

HOCH2CH2 H 3-C1 4-Cl Cl Cl 143-145 NC H 3-C1 4-Cl Cl Cl 251-252 5 C6H5CH2OCH2 H 3-Cl 4-Cl Cl Cl 88-89

Cl ° ~ CH2 H 3 -Cl 4_Cl C1 Cl 118 “120 IC = C-CH2 H 3 -Cl 4-Cl Cl Cl 115-116 CH3 HH 4-Cl Br CF3 126-129 C2H5OCH2 HH 4-Cl Br CF3 91- 92 10 C2H5-OCH2 H 3-Cl 4-Cl Cl Cl 118-120 C2H5-OCH2 HH 4-Cl Br Br 104-105 C-Hc-CH_ HH 4-Cl Br Br 81-82

O D Z

CH3 HH 4-Cl Br Br 197-201 CN HH 4 — cf3 Cl Cl 138-139 15 C2H5-OCH2 HH 4 ”CF3 Br CF3 104-105 C2H5-OCH2 HH 4“ CF3 H CF3 76-77 C2H5OCH2 H 3-Cl 4-Cl Br CF 3 80-81 20 Example 10 1-Benzyl-4,5-dibromo-2- (oC, rj, r <, - trifluoro-p-tolyl) pyrrole-3-carbonitrile

Br CN

• 25 \ / A 'Λ // j \ + K0C (CH3) 3 + CHaBr -► BrCFj

Br -CF 3 ό 30 In a 100 ml flask, 1.5 g of 4,5-dibromo-2- (od, nl - ·· trifluoro-ε-tolyl) pyrrole-3-carbonitrile are mixed with 50 ml of dry THF, giving a clear dark solution. Add with stirring 1 eq. K0tBu added. After a few minutes, the solution clears. Add 35 benzyl bromide (0.65 g) via syringe. The mixture is heated to reflux overnight. The next day, TLC (ethyl acetate / hexane 50/50) shows the presence of both starting material and product. The reaction mixture is further treated as follows; 50 ml of water are added and the mixture is extracted with 5 x 50 ml of CHCl3. The organic phases are combined and washed with 4 x 50 ml of 10% aqueous NaOH solution. The organic phase is dried over MgSO 4 and evaporated to dryness. This gives a brown solid which is crystallized from ethyl acetate / hexane.

Yield = 0.75 g = 40.7%

Mp = 145-147 ° C with decomposition.

Example 11 4,5-Dichloro-2- (3,4-dichlorophenyl) -1- (ethoxymethyl) pyrrole-3-carbonitrile 15

ci _ CN

+ K0C <CH3) 3 + C ICHjOCgHg -121 * Cl CHeOC2H5 Cj 20 ci 4,5-dichloro-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile sample (1.0 g, 0.003 mol) is dissolved in 10 ml: dry tetrahydrofuran. To this solution is added potassium t-butylate (0.37 g, 0.0033 mol) followed by chloromethyl ethyl ether (0.312 g, 0.0033 mol). The mixture is stirred for about an hour at room temperature and then poured into a large volume of water which precipitates the product. The white solid is collected and dried to give 1.0 g (91%) of product, mp 128-130 ° C.

Example 12 4-Chloro-3-cyano-2- (p-chlorophenyl) pyrrole

C1 cn ci CN

35 r-t * M. W

_ · * "*“ C1-- «» NfV «V \ TVc.

! h ci dioxane v = / \ = J

47 91525

To a magnetically stirred solution of 17.87 g (88.2 mmol, 1.00 equivalents) of 2- (E-chlorophenyl) -3-cyanopyrrole in 800 ml of dioxane at 20 ° C is added dropwise over 30 minutes. 250.15 g (13.13 g of solid, 176.4 mmol, 2.00 equivalents) of 5.25% by weight of bleach.

After stirring for a further 30 minutes at room temperature, the reaction solution is poured into 2200 ml of water. The resulting mixture is filtered under vacuum to remove a small amount of black solid. The filtrate is acidified to pH 2 with concentrated HCl to give a brown solid. This solid is filtered off in vacuo and the collected solids are washed with water to give 22.41 g of a brown solid. This solid is treated with 100 mL of 5% aqueous sodium hydroxide to dissolve the bulk of the material, leaving a small amount of insoluble black solid. This black solid, dissolved in 100 mL of ethyl acetate, is washed with 75 mL portions of 5% aqueous NaOH, water, and saturated aqueous NaCl. The ethyl acetate layer is dried (MgSO 4), treated with charcoal, filtered, and then evaporated to dryness on a rotary evaporator in vacuo to give 1.10 g (yield-13 to 5.3 4) of an orange-brown solid. This solid was recrystallized from ethyl acetate-chloroform to give 0.51 g (2.4% yield) of an off-white solid, 4-chloro-3-cyano-2- (p-chlorophenyl) pyrrole, mp 251- 253.5 ° C.

30 Example 13

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

Π λ dioxane n — r \ / f \ + Br2 - * Ji \\ 35 XN / \ yy— \ Br «A.

A sample of H '(ί y-c 1 y-cl ci ci 48 91523 2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile (2.0 g, 0.008 mol) is dissolved in 100 ml of dioxane by heating 4 The solution is then cooled to 30 and bromine (1.3 g, 0.008 mol) is added, and after stirring for 1 hour at room temperature, the solution is poured into water and a gray solid (2.2 g, 88 %) is collected, mp 233-236 ° C, dec.

In a similar manner, 5-bromo-2- (3,4-dichloro) -3-nitropyrrole can be prepared starting from 2- (3,4-dichlorophenyl) -3-nitropyrrole.

Example 14 Preparation of 5-bromo-4-chloro-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile

15 CN C1 \ _ / CN

f / ~ \ + <CH3> 3C0C1 - * II 'λ

A sample of Br 2 Cl 2 Cl 5 -bromo-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile (0.158 g, 0.005 mol) is dissolved in tetrahydrofuran (5 mL). An equivalent amount of t-butyl hypochlorite is added and the solution is stirred overnight. The solution is poured into water and the precipitate (0.052 g, 30%) is collected. Mp> 275 ° C.

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

Example 15 5-Bromo-4-chloro-2- (p-chlorophenyl) -pyrrole-3-

carbonitrile production Cl CN Cl CN

35 + ΒΓ * 2 CHCl 3 C

H Ν ^ Λ-Cl Br H Ν ^ Λ-Cl 49 91523

To a magnetically stirred solution at 22 ° C of 0.17 g (0.67 mmol, 1.00 equivalents) of 4-chloro-2- (E-chlorophenyl) pyrrole-3-carbonitrile in 100 mL of chloroform is added dropwise over 30 minutes a solution of 0.20 ml (0.62 g, 3.88 mmol, 5.79 equivalents) of bromine in 5 ml of chloroform. The addition does not cause exotherm. After stirring for 1 1/4 hours at room temperature, the clear red reaction solution is evaporated to dryness in vacuo to give 0.28 g of an off-white solid. This solid is slurried with hexane-methylene chloride to give 0.23 g of an off-white fluffy solid in vacuo; mp 262-263 ° C; with decomposition.

Example 16 Preparation of 5-chloro-4-bromo-2- (p-chlorophenyl) pyrrole-3-carbonitrile

CN Br \ CN

20 CHCl 3 Cl 2 -ci '25 To a magnetically stirred solution at 45 ° C of 1.00 g (4.22 mmol, 1.00 equivalents) of 5-chloro-2- (E-chlorophenyl) pyrrole-3- carbonitrile in 300 ml of chloroform, a solution of 0.40 ml (1.24 g, 7.76 mmol, 1.84 equivalents) of bromine in 25 ml of chloroform is added dropwise over 30 minutes. The addition does not cause exotherm and a small amount of solid begins to precipitate at the end of the addition. After stirring for 19 1/2 hours at room temperature, the reaction mixture is evaporated to dryness in vacuo to give 1.49 g of an orange-white solid.

t · 50 91525 This solid is slurried with hexane-methylene chloride to give 1.33 g (100% yield) of a fluffy white solid under vacuum filtration; mp 250-258 ° C, dec.

Example 17 Preparation of 5-chloro-2- (p-chlorophenyl) pyrrole-3-carbonitrile

CN CN

ηη, _ / HOflc, _ / 10 / T% + S0eCl2 —- JT \ —Cl C1 —Cl to a magnetically stirred solution at 35 ° C of 2.40 g (11.8 mmol, 1.00 equivalents) of 2- (p-chlorophenyl) pyrrole-3-carbonitrile and 65 mL of glacial acetic acid, 0.75 mL (1.26 g, 9.34 mmol, 0.79 equivalents) of sulfuryl chloride is added dropwise via syringe over 5 minutes. . Approximately 5 minutes after the end of the addition, a solid precipitated from the reaction solution. After stirring for 45 minutes at room temperature, the reaction mixture is filtered and the collected solid is washed with very cold acetic acid to give 2.08 g (crude Santo 74%) of an off-white solid. This solid is recrystallized from 75 ml of hot acetic acid to give 1.63 g (58% yield) of 97% by weight pure product; mp 258.5-261 ° C.

Example 18 Preparation of 2- (3,4-dichlorophenyl) -1-methylpyrrole-3-carbonitrile

CN

CN _ / n— / Cl + KOC (CH3) 3 + CH3I-► 35 h CH3 \ = / li 91523 51 2.0 g in a 100 ml flask 2.0 g of 2- (3,4-dichlorophenyl) -pyrrole-3-carbonitrile dissolve in 50 ml of dry THF and add 1 equivalent of potassium t-butylate.

This forms a slightly turbid solution. One equivalent of methyl iodide is then pipetted into the mixture li-5. This causes a slight lightening of the color. A drying tube is connected to the flask and stirred at ambient temperature overnight.

The next morning, the bottle contains a faint pale-10 colored precipitate. 50 ml of water are then added and the solution clarifies before a solid precipitates out of solution. This solid is filtered off from solution and compared to the starting material by TLC (25% ethyl acetate in hexane). This shows a new single spot 15 which moves faster than the starting material. It is dried in a vacuum oven at 50 ° C overnight. 1.31 g of product are obtained or the yield is 62% and its melting point is 140-142 ° C.

Example 19 Preparation of 4,5-dichloro-2- (3,4-dichlorophenyl) -1-methyl-pyrrole-3-carbonitrile

CN Cl CN

n ~ {Cl + SO2Cl2 -► F ~ \, cl 25 Y \ fiLcl = ιΛτγν «CHj \ - / CH3 v = / in a 50 ml round bottom flask 0.5 g of 2- (3,4-dichlorophenyl) -1- methylpyrrole-3-carbonitrile is mixed with 35 ml of glacial acetic acid. The mixture is gently heated in a heater to dissolve any pyrrole.

To this clear solution is added by pipette 2 eq. sulfuryl chloride. The solution is stirred at room temperature for 12 hours. After 12 hours, the solution is poured into 50 ml of water, resulting in the formation of a white precipitate. This is filtered off and dried in a vacuum oven at 50 ° C for 3 hours.

The solid obtained is identical to the product of Example 9 by TLC (25% ethyl acetate in hexane) and infrared analysis. The product yield is 0.36 (56%).

Example 20 Preparation of 4,5-dichloro-2- (3,4-dichlorophenyl) -1- (2-hydroxyethyl) pyrrole-2-carbonitrile 10

Cl CN

W

cl - ^ \ + BrClCHOH + K + (^ - t-Bu-►

15 H

Cl CN

20 k

OH

To a stirred mixture of 2.0 g (6.5 mmol) of 4,5-dichloro-2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile and 0.88 g (7.8 mmol) potassium tert-butylate and which is heated to boiling in 50 ml of dioxane, 0.98 g (7.8 mmol) of bromoethanol are added. The mixture is stirred at reflux for 12 hours, cooled, diluted with 50 ml of water, and extracted several times with chloroform.

The combined chloroform extracts are dried over magnesium sulphate and evaporated to dryness in vacuo to leave a solid which, on heating and dissolving in ethyl acetate, precipitates on cooling most of the starting pyrrole. By evaporating the mother liquor to dryness and

II

53 91 523 recrystallization of the remaining solid from 20% ethyl acetate in hexane gives 0.31 g of a white solid, mp 143-145 ° C; IR 5077A. Analysis for C 18 H 18 N 2 O 2: 5 Calculated: C 44.57, H 2.29, N 8.00, Cl 40, 57%

Found: (Agm 33139): C 44.77, H 2.29, N 8.09, Cl 40.14%

Example 21 Preparation of 4,5-dichloro-2- (3,4-dichlorophenyl) pyrrole-1,3-dicarbonitrile 10

Cl CN

v_y

Cl-'X / CNBr + K + t "Bu0 ~ - H '' ^ / ^ Cl 15

Cl CN

20 I ^^ Cl

CN

Potassium t-butylate (617 mg, 55 mmol) is added portionwise to a solution of 3-cyano-4,5-dichloro-2- (3,4-dichlorophenyl) pyrrole (1.52 g, 5 mmol). 25 lia) in dry THF (20 ml). After 30 minutes, a solution of cyanogen bromide (583 mg, 5.5 mol) in THF (1 mL) is added. The reaction mixture is kept at room temperature overnight. The solvent is removed on a rotary evaporator. The residue is treated with water and extracted with ethyl acetate. The organic layer is washed with water and brine and dried (MgSO 4). Evaporation to dryness and crystallization of the residue from ethyl acetate gave white crystals (1.07 g); mp 250.5-252.0 ° C; IR (nujol) 2255, 2245 cm-1 (CN); 13 C NMR 35 (DMSO-d 6) 102.7 (N-CN), 113.7 (3-CN); mass spectrum 331.9 (M + 1).

54 91523

Analysis for compound (330.99):

Calculated: C 43.54, H 0.91, N 12.70, Cl 42.85%

Found: C 43.62, H 0.93, N 12.63, Cl 41.95%

Example 22 4,5-Dichloro-2- (3,4-dichlorophenyl) -1- (3-iodo-2-

propynyl) -pyrrole-3-carbonitrile Cl 2 -, CN

1 [f / ^ / cl · 10 ciANAr ^ Y + I2 + NaOH -

Λ c \ / CN

N V_ / i5 i Cl

^ CHI

To a stirred mixture of 1.91 g (5.5 nunol-20) of 4,5-dichloro-2- (3,4-dichlorophenyl) -1- (2-propynyl) pyrrole-3-carbonitrile 500 in methanol, 69 ml of 10% aqueous sodium hydroxide solution and then 0.70 g (2.7 mmol) of iodine are added. The mixture is stirred for 12 hours and then acidified and diluted with 200 ml of water. The precipitated solids are collected and recrystallized from methanol to give 0.51 g of crystals, mp 115-116 ° C.

This reaction is also applicable to the conversion of any of the substituted N-alkynylarylpyrroles of formulas III, IV, V, VI or VII of this invention to the N-substituted 3-iodo-2-propynylarylpyrroles of said invention.

Example 23 Preparation of 2, (3,4-dichlorophenyl) -4,5-diiodopyrrole-3-carbon-35-nitrile • «55 91523

/ CW o * \ / CN

• l [^ C · ¢ - - '^ C

o N-Ioduccinimide (5.7 g, 0.0254 mol) is slowly added to a solution of 2- (3,4-dichloro-10-phenyl) -pyrrole-3-carbonitrile (3.0 g, 0.0127 mol) In 100 mL of THF. The reaction mixture is stirred for several hours at 25 ° C until thin layer chromatographic analysis (silica gel; ether: petroleum ether: acetic acid = 100: 100: 1) indicates that the reaction is complete. The mixture is evaporated in vacuo to give a residue containing pyrrole and succinimide. The crude solid is dissolved in 500 ml of ether and shaken with 5 x 400 ml of water to remove succinimide. The ether is dried over Na2SO4 and evaporated to dryness in vacuo to leave 2.0 g (32.3%) of a gray-brown solid, m.p. 230 DEG C. (purple fumes).

Example 24 Preparation of 2-phenyl-1-pyrroline-4-carbonitrile 25

NC

/ CN / N \ I ΙΪ10 mo1 * "Bu4N + F_) -v = / + TMS - / JJ-1-> / \

THF / 16hr / RT

s »\\ J

30 \

A solution of acrylonitrile (0.65 mL; 0.01 mol) and N- (trimethylsilyl) methyl S-methylbenzenethiimidate (2.4 g, 0.0 mol) in THF (100 mL), 35 is cooled to -5 ° C in an ice-acetone bath. A solution of tetrabutylammonium fluoride (1.0 ml of 1N THF solution) and THF (20 ml) is added dropwise over 30 minutes as a nitrogen blanket. The solution is stirred for another 30 minutes at -5 ° C, and then allowed to slowly warm to ambient temperature. Stirring is continued for a further 18 hours and then the solvent is removed in vacuo. The residue is partitioned between ether and water and the aqueous layer is extracted with fresh ether. The combined organic layer is washed with water, then saturated sodium chloride solution. The solution is dried over MgSO 4 and cooling of the filtrate causes a precipitate of an off-white solid (1.2 g, 70% of theory) with spectral properties identical to those described by Tsuge (J. Org. Chem. 52, 2523 (1987)).

Analysis for cnHioN2:

Calculated: C 77.65, H 5.88, N 16.47%

Found: C 77.55, H 5.83, N 16.39%

Mp = 95-97 ° C.

Example 25 Preparation of 2-phenyl-pyrrole-4-carbonitrile

NC

25 DDQ / CmE / pyr \

16 h / h.l. NH

Nitrogen-protected 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (0.23 g, 0.001 mol) and 2-phenyl-1-pyrroline-4-carbonitrile (0.17 g; 0.001 mol) dissolved in 1,2-dimethoxyethane (13 ml) to give a clear orange solution. Pyridine (0.08 ml; 0.001 mol) is added in one portion, causing a slight

II

91523 57 exothermic reaction (to about 28 ° C) and a green-gray precipitate immediately formed. The suspension is stirred at room temperature for 18 hours during which time much of the solvent evaporates. The brownish semi-solid residue is partitioned between ether-5 ter and half-saturated sodium carbonate solution. The red-brown aqueous layer is extracted twice with ether and the combined ether layer is washed with fresh water, then saturated sodium chloride solution. After drying over MgSO 4, the solvent 10 is removed in vacuo to give a white semi-solid. This material was recrystallized from ethylene dichloride (DARCo treatment) to give lavender blue crystals (0.1 g).

The identical product is obtained directly in one step by condensing oC-chloroacrylonitrile and N- (trimethylsilyl) methyl S-methylbenzenethioimidate using a tetrabutylammonium fluoride catalyst (analogous to the preparation of 2-phenyl-1-pyrroline-4-carbonitrile described previously).

Analysis for cnH8N2:

Calculated: C 78.57, H 4.76, N 16.67%

Found: C 78.65, H 4.70, N 16.43%

Mp = 155-158 ° C.

Example 26 Preparation of 2,4-dibromo-5-phenyl-pyrrole-3-carbonitrile NC NC Br 30 Br2 / CHCl3 NH \ W) -Λη \\ ^)

Under nitrogen, a solution of bromine (0.6 mL; 35 0.012 mol) in CHCl 3 (5 mL) is added dropwise over 20 minutes to a stirred solution of 58,91523 2-phenyl-pyrrole-4-carbonitrile (0.84 g; 0.05 mol) in CHCl 3 (20 ml). The resulting solution is stirred for 18 hours at room temperature, then the solvent is removed in vacuo to give a solid which is recrystallized from C 2 H 2 Cl 2 (DARCO treatment) to give the desired final product (0.6 g); mp = 239-242 ° C. Analysis for the compound

Calculated: C 40.49, H 1.84, Br 49.08, N 8.59%

Found: C 39.88, H 1.87, Br, 48.81, N 8.48% By the method described in Examples 24, 25 and 26, 2,4-dibromo-5- (and-chlorophenyl) pyrrole 3-carbonitrile; mp 270-272 ° C (dec.).

Example 27 3 ', 4'-Dichloro-3- (1,3-dioxolan-2-yl) -propio-phenone "or ..... * ι 20 Cl 0

J

25 Cl ^

To a rapidly stirred mixture of magnesium turnings (0.64 g, 26 mmol) in 10 mL of tetrahydrofuran at 25 ° C in a 100 mL three-necked round bottom flask equipped with a thermometer at 60 mL. with an addition funnel, and a nitrogen inlet tube, is added dropwise 2- (2-bromoethyl) -1,3-dioxolane (4.7 g, 26 mmol) in 40 mL of tetrahydrofuran. The addition rate is adjusted so that the reaction temperature is kept below 50 ° C. The reaction mixture is then stirred at 91523 for 59 hours at 25 ° C. 120 ml of tetrahydrofuran are mixed with potassium 3,4-dichlorobenzoate (5.0 g, 22 mmol) under nitrogen. The Grignard solution is then rapidly decanted from the unreacted magnesium turnings, 5 and added dropwise to the rapidly stirred potassium benzoate suspension. The reaction mixture is then stirred for 24 hours at 25 ° C. Fifty ml of diethyl ether and 15 ml of 3-norm are added to the reaction mixture. hydrochloric acid and the layers are separated. The organic layer is washed with saturated aqueous sodium hydrogencarbonate solution until neutral, then washed once with 10 ml of saturated brine. Drying over sodium sulfate and evaporation to dryness on a rotary evaporator gives a beige semi-solid which is chromatographed on silica gel using 3: 1 hexane-ethyl acetate as eluent to give the ketoacetal (4.3 g, 60%) as a white solid; mp 115-117 ° C.

Example 28 Preparation of 3- (3,4-dichlorobenzoyl) propionaldehyde O 0 H 2 O 3 / H 2 O 2 H 2 O / ETOH / JO 3 CHO

Ten grams (26 mmol) of 3 ', 41-dichloro-3- (1,3-dioxolan-2-yl) -propiophenone are added to 30 ml of 0.2 mol. oxalic acid (prepared by dissolving 0.9 g of ox, 30 hydrochloric acid dihydrate in 30 ml of water) and 5 ml of ethanol. The mixture is boiled for one hour and then allowed to cool. Most of the ethanol is evaporated off on a rotary evaporator and 100 ml of diethyl ether are added together with 20 ml of saturated aqueous sodium hydrogen carbonate solution. The layers are separated and the organic phase is dried over magnesium sulphate. Evaporation to dryness on a rotary evaporator gives a viscous yellow oil which is chromatographed on silica gel using hexane-ethyl acetate 3: 1 to give the keto-5 aldehyde (6.3 g, 75%) as a white solid. Example 29 Preparation of 2- (3,4-dichlorophenyl) pyrrole 0 10 Cl NH 4 ORC-Cl OCHO ETOH ([

To a suspension of 3- (3,4-dichlorobenzoyl) propionaldehyde (6 g, 26 mmol) in 60 mL of absolute ethanol is added ammonium acetate (4 g, 52 mmol). The reaction mixture is boiled for 20 minutes and allowed to cool. Most of the ethanol is evaporated off on a rotary evaporator and 200 ml of a 1: 1 mixture of dichloromethane and diethyl ether and 50 ml of water are added. The layers are separated and the organic phase is dried over sodium sulfate. Evaporation to dryness on a rotary evaporator gives a dark brown oil which is chromatographed on silica gel using a 3: 1 mixture of hexane and ethyl acetate as eluent to give pyrrole (4.6 g, 83%) as a light brown solid; mp 49-51 ° C.

Example 30 Preparation of 5- (3,4-dichlorophenyl) pyrrole-2-carboxyaldehyde ___ Cl I-- Cl ^ N / Sfn 15 DnF / pcci3 Αντυτη

35 H H 2 Cl 2 - H HCl

E) Naoflc 91523 61 To 10 ml of dimethylformamide, which is stirred under a nitrogen-protected 50 ml round-bottomed flask, is added dropwise phosphorus oxychloride (0.6 ml, 6.5 mmol) by syringe. The solution warms up and turns pale yellow in color. It is stirred for 20 minutes before 2- (3,4-dichlorophenyl) pyrrole (1 g, 4.7 mmol) is added portionwise. The resulting beige suspension is stirred for 30 minutes before heating at 50 ° C for 40 minutes. To the cooled reaction mixture 10 is added a solution of sodium acetate (10 g, 122 mmol) in 15 mL of water, which is then stirred for 20 minutes. The beige precipitate is filtered off from the reaction mixture and air dried for 20 hours to give essentially pure aldehyde (1.1 g, 95%), 15 mp> 200 ° C.

Example 31 Preparation of 5- (3,4-dichlorophenyl) pyrrole-2-carbonitrile 20 __ Cl .-- Cl

H 2 N-0S0, H

0HC'-Y \\ 2 3, \\ H Vc ^ / ^ ci ETOH / Hg0 H Vi ^ / ^ Cl 1 To a suspension of 5- (3,4-dichlorophenyl) pyrrole-2-carboxaldehyde (1, 5 g, 6.2 mmol) in 20 mL of water and 20 mL of ethanol, hydroxylamine-O-sulfonic acid (0.7 g, 6.2 mmol) is added. The reaction mixture is boiled for one hour, during which time a gray precipitate appears. After allowing the reaction mixture to cool, it is filtered to give essentially pure nitrile (1.5 g, 99%) as a gray solid, mp 170-171 ° C.

Example 32 35 Preparation of 3,4-dibromo-5- (3,4-dichlorophenyl) pyrrole-2-carbonitrile 62,91523

Br Br

Cl \ - (ci

yy VV> - / NBS // \ V

\\ -1 \ V

5 H V ^ / ^ Cl THF Vc ^ / ^ Cl

To a solution of 5- (3,4-dichlorophenyl) pyrrole-2-carbonitrile (0.5 g, 2.1 mmol) in 20 mL of 10 tetrahydrofuran under nitrogen is added portionwise N-bromo-succinimide (0.8 g). , 4.2 mmol). The reaction mixture is stirred at 25 ° C for 30 minutes before 10 ml of water and 40 ml of diethyl ether are added. The layers are separated and the organic layer is dried over sodium sulfate. After evaporation to dryness on a rotary evaporator, chromatograph on silica gel using hexane-ethyl acetate 3: 1 as eluent to give dibromopyrrole (0.5 g, 60%) as a brown solid, mp> 259 ° C.

Example 33 Preparation of 4-phenylpyrrole-3-carbonitrile CN 2, SO 2, CT

YJO

30 Ky

*: H

To a mixture of 5.0 g (39 mmol) of cinnamonitrile and 7.6 g (39 mmol) of (E-tolylsulfonyl) methyl-35-isocyanide in 35 ml of DMSO and 65 ml of ether are added 63,91523 Over 20 minutes, a suspension of 1.86 g of a 60% suspension of sodium hydride in oil (1.11 g; 46 mmol) in 80 ml of ether. The reaction mixture is kept under nitrogen for one hour and then diluted with ether and water. The ether layer is separated, dried over magnesium sulfate, and evaporated to dryness in vacuo.

The resulting oil is chromatographed on silica gel using 1: 1 chloroform-ethyl acetate to give 2.5 g of a cream solid. Recrystallization from ether-hexane gives 1.15 g of product, mp 123-125 ° C; NMRM86-1077. Literature: Tet. Letters 5337 (1972): mp 128-129 ° C.

Example 34 Preparation of 2,5-dichloro-4-phenylpyrrole-3-carbonitrile

\ jD \ _jD

20 + SOoCU - »N Cl N Cl

H H

To a stirred mixture of 0.66 g (3.9 mmol) of 4-phenylpyrrole-3-carbonitrile in 20 mL of dry THF cooled to 6 ° C with an ice bath is added 0.66 mL (1, 11 g, 8.2 mmol) of sulfuryl chloride over 4 minutes. The mixture is kept at 5-40 ° C for another 45 minutes and then stirred for another 30 minutes in the absence of an ice bath. After pouring the reaction mixture into 80 ml of ethyl acetate and 40 ml of water, the organic phase is separated, washed with water, and dried over sodium sulfate. Filtration through a short column of silica gel, rinsing with ethyl acetate, and evaporation of the combined filtrates to dryness in vacuo gave 0.9523 g of a dark solid. Recrystallization from chloroform gives 0.42 g of off-white crystals, mp 195-196 ° C; (With decomposition).

Analysis for Compound 5 Calculated: C 55.72, H 2.55, N 11.82, Cl 29.91%

Found: C 55.66, H 2-65, N 11.69, Cl 29.97%

Following the procedures of Examples 33 and 34, the following analogous compounds are prepared. For the synthesis of 2,6-dibromo-4- (p-chlorophenyl) pyrrole-3-carbonitrile, the procedure of Example 33 is followed using bromine in dioxane instead of sulfuryl chloride in tetrahydrofuran.

yjy y N x

B

R X Y s p ° C; 25 4-Cl Cl Cl 237-240 (ha].) 4-CH3 Cl Cl 103-206 4-Cl Br Br> 245 ° 30

Example 35

Ethyl 4- (p-chlorophenyl) pyrrole-3-carboxylic-methacrylate

II

65 91523 p

+ NaH

5 C1v ^ n

Xxxr ~

B

To a mixture of 5.63 g of a 60% suspension of sodium 10 hydride / oil in 200 ml of dry ether under nitrogen is added a mixture of 23.5 g (122 mmol) of ethyl p-chlorocinnamate and 19.4 g ( 122 mmol) (E-tolylsulfonyl) methyl isocyanide as a solution in 180 ml of ether and 80 ml of dimethylsulfonide. 15 The addition time is about 20 minutes and causes the mixture to boil slightly. After stirring for a further 10 minutes, the mixture is diluted with 100 ml of water. The mixture is extracted four times with ether which is then dried over magnesium sulphate and then evaporated to dryness in vacuo. The resulting solid is recrystallized from ethylene dichloride to give 7.8 g of crystals, mp 137-138 ° C.

Analysis for C 12 H 20 N 2 O 2 (Calculated: C 6253, 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 until crystallization leaves more crude ester which is transferred to the saponification step.

Example 36 Preparation of 3- (p-chlorophenyl) pyrrole V-'Vl

B

35 C1

B

66 91523

A mixture of 22.0 g of crude ethyl 4- (E-chlorophenyl) pyrrole-3-carboxylate obtained from the recrystallization of the mother liquor and the recrystallized product obtained from the previous step is stirred at reflux for 2.5 hours with 150 ml. 10% aqueous sodium hydroxide solution. The mixture is cooled, extracted with ether, and acidified to give a precipitate which, when combined and dried, weighs 11.6 g.

A mixture of 10.5 g of acid in 100 ml of β -eta-10 nolamine is heated at reflux for three hours. After cooling, the mixture is poured into 400 ml of ice and the resulting mixture is extracted four times with chloroform. After drying over magnesium sulfate and treatment with activated charcoal, the chloroform solution is evaporated to dryness in vacuo to leave a brown solid. Chromatography on silica gel using 1: 1 ethyl acetate-hexane gives 4.0 g of a white solid, mp 117-118 ° C.

Example 37 Preparation of 3- (p-chlorophenyl) -pyrrole-2-carboxaldehyde jf n_ / Il 25 + <coci> 2 + <ch3> 2nch— \ N / 'ο®'ϋ \ n / ^ - cho

B

To a mixture of 0.86 g (12 mmol) of dimethylformamide in 10 ml of ethylene dichloride, which is kept under nitrogen and cooled in an ice bath, is added 1.49 g (12 mmol) of oxalyl 91523 67 chloride over 25 minutes. in ml of ethylene dichloride. The ice bath is removed, the mixture is stirred for another 5 minutes and re-cooled in an ice bath. To this mixture is added 1.5 g (8.5 mmol) of 3- (E-chlorophenyl) pyrrole in 25 ml of ethylene dichloride over 20 minutes. The ice bath is removed and, after stirring for a further 30 minutes, the mixture is poured into 50 ml of ice water and 6 ml of 50% sodium hydroxide solution. The resulting mixture is extracted with ether and chloroform and the combined organic mixture is dried over magnesium sulfate and evaporated to dryness in vacuo.

Purification of the resulting solid by chromatography on silica gel using 1: 1 ethyl acetate-hexane gives 0.63 g of an off-white solid which is used directly for conversion to 3- (p-chlorophenyl) -15 pyrrole-2-carbonitrile.

Example 38 Preparation of 3- (2-chlorophenyl) -pyrrole-2-carbonitrile ”/ f + H2NSO3H ->

: 25 Jj CH = 0 N CN

A mixture of 0.63 g (3.1 mmol) of 3- (E-chlorophenyl) pyrrole-2-carboxaldehyde in 10 ml of water is stirred and cooled on ice with the slow addition of 0.52 g (4.6 mmol) of hydroxylamine-O-sulfonic acid in 10 ml of water. After the addition, the cooling bath is removed and the mixture is heated for 25 minutes. After cooling, the solid obtained is collected and shown, by NMR, to be a mixture of the product and the starting aldehyde. This mixture is reacted in a similar manner with 68,91523, adding 0.49 g (4.2 mmol) of hydroxylamine-O-sulfonic acid in a total of 30 ml of water. The mixture is heated at 60-70 ° C for 2 hours. The mixture is cooled and the solids formed are collected and purified by chromatography on silica gel using 1: 1 ethyl acetate-hexane to give 0.40 g of a pink solid, mp 114-115 ° C.

Example 39 Preparation of 4,5-dibromo-3- (p-chlorophenyl) pyrrole-2-carbo-10-nitrile. > · ^ 1 Z1 15 BrY- ^ + Br2 - *

H CN Br H CN

20

To a mixture of 0.40 g (2.0 mmol) of 3- (E-chlorophenylpyrrole) -2-carbonitrile in 25 mL of chloroform is added 0.63 g (4.0 mmol) of bromine. After 20 minutes to 25 minutes, the precipitate formed is collected and recrystallized from ethyl acetate to give 0.21 g of pink crystals, mp> 250 ° C.

Analysis for C 1-4 H 2 B 2 CIN:

Calculated: C 36.62, H 1.39, Br 44.38, Cl 9.85, N 7.77% Found: C 36.92, H 1.32, Br 44.62, Cl 9.88, N 7.50%

Example 40

Preparation of ethyl 5-bromo-4- (p-chlorophenyl) pyrrole-3-carboxylate 91523 69

O

"

/ “Λ / c- ° c2h5 II

“$ 0. o 'ή

H II

o 10 r — λ / COOCgHg

Br N - 11 Ethyl 4- (E-chlorophenyl) pyrrole-3-carboxylate (1.6 g, 0.0064 mmol) is dissolved in tetrahydrofuran (40 mL). At 25-28 ° C, N-bromo-succinimide (1.14 g, 0.0064 mmol) is added in small portions. After the addition is complete, the solution is stirred overnight at room temperature.

The solution is evaporated to dryness in vacuo and the solid residue is partitioned between water and ether. The ether layer is separated and dried over magnesium sulfate. Further treatment of the ether extract left 1.9 g (90%) of a white solid which was purified by stirring with a mixture of hexane and ethyl acetate in a ratio of 80/20. The insoluble solid (1.3 g, 62%) is collected and has a mp of 161-164 ° C.

Analysis for ci3HnBrClN025

Calculated: C 47.50, H 3.34, N 4.26, Br 24.33, Cl 10.80% Found: C 47.39, H 3.38, N 4.12, Br 24.29, Cl 10.77%

Example 41 Preparation of 5-bromo-4- (p-chlorophenyl) pyrrole-3-carboxylic acid 70 91523 cl_fVrY C0 ° CaH5 cia = / ~ j3 .1M Ni0 „_ 5 B <Y · <Υ

Ethyl 5-bromo-4- (p-chlorophenyl) pyrrole-3-carboxylate (15 g, 0.045 mmol) is added to 200 mL of 10% sodium hydroxide and the slurry is heated to reflux. When everything appears to be dissolved, boil the mixture for another 40 minutes. The mixture is cooled, filtered and the filtrate is acidified. The white precipitate (8.0 g, 58%) is collected and dried. The mp of the solid is> 205 ° C and NMR (d 6 -DMSO) reveals 7.72 (d) for the pyrrole proton. The mass spectrum is also consistent with the monobrominated compound.

Example 42 Preparation of 2-bromo-3- (p-chlorophenyl) pyrrole 20

C1_ <rv / COOH

\ = / Jl ^ y h2nch2ch2oh \ = y

Br JJ * H

5-Bromo-4- (p-chlorophenyl) pyrrole-3-carboxylic acid (8.0 g, 0.026 mmol) is added to aminoethanol (24 mL) and the slurry is slowly warmed to 110-120 ° C and maintained at that temperature for one hour. I drive. The solution is cooled and poured into water and extracted with ether. The ether extract, flash chromatography (hexane / ethyl acetate 75/25) shows a larger fast moving spot and a slower moving smaller component. Further work-up of the ether portion left a dark solid (4.0 g, 56%) which is 2-bromo-3- (p-chloro-phenyl) pyrrole and was used immediately to give 5-bromo-4- (jd). -

II

91523 71 chlorophenyl) pyrrole-2-carbonitrile. Example 43 Preparation of 5-bromo-4- (p-chlorophenyl) pyrrole-2-carbonitrile C1 A D "E C1 / Vr-.

\ = slH \ + C1S ° 2NCO + DMF—

Br h Br h 10 A freshly prepared sample of 2-bromo-3- (p-chlorophenyl) pyrrole (4.0 g, 0.015 mmol) is dissolved in dry dimethoxyethane (25 mL). Chlorosulfonyl isocyanate (3.08 g, 0.022 mmol) is then added, keeping the temperature below 25 ° C. After stirring overnight, the solution is treated with dimethylformamide (6 mL) and stirred for 3 hours. Finally, the solution is poured into water to precipitate a brown solid (3.8 g, 90%). Chromatography on a dry column (hexane / ethyl acetate = 80/20) gives 1.4 g (33%) of a white solid, m.p. 202-204 ° C.

Analysis for C 18 H 9 BrClN 2:

Calculated: C 46.90, H 2.13, N 9.95, Cl 12.61, Br 28.39% Found: C 47.20, H 2.09, N 9.80, Cl 12.36, Br 27.42%

Example 44 Preparation of 3,5-dibromo-4- (p-chlorophenyl) pyrrole-2-carbonitrile

Cl— (f y — r — v + BrP dioctane Cl — v v ~~~ 7— \ x = / JP \ 1- * \ = / // \\

3 Br 1, r'CN Br N ^ 'CN

Br H Br H

A sample of 5-bromo-4- (p-chlorophenyl) pyrrole-2-carbonitrile (2.2 g, 0.0078 mol) is dissolved in 30 ml of dioxane. The solution is warmed with bromine (1.3 g, 0.008 72 91523 moles) in dioxane (20 mL) and then stirred overnight at room temperature. The reaction mixture is poured into water to precipitate a tan solid (2.6 g, 92%). A portion thereof (1.6 g) is purified by flash chromatography using hexane / ethyl acetate 75/25 to give 0.8 g of a gray solid, mp 191-194 ° C.

Analysis for C 11 H 12 Br 2 ClN 2:

Calculated: C 36.61, H 1.38, N 7.76, Cl 9.84, Br 44.3% Found: C 37.46, H 1.25, N 7.41, Cl 9.53, Br 42.99%

Example 45 Preparation of 3- (3,4-dichlorophenyl) -4-nitropyrrole 15 δ ____ "NC + NaH-

AJ; AJ

Cl ch3 Λ “- ° g \ A /

; B

25

Sodium hydride (2.66 g of a 60% oil suspension rinsed with dry ether; 66 mmol) is suspended in 150 ml of dry ether. To this mixture is added over 15 minutes a mixture of 12.0 g (5.5 mmol) of 3,4-30 dichloro-p-nitrostyrene and 10.8 g (5.5 mmol) of (E-tolylsulfonyl) methyl isocyanide in 50 ml of DMSO and 150 ml of ether. The mixture is stirred for 1.5 hours and then diluted with 150-200 ml of water and added ether. The ether layer is separated, dried over magnesium sulfate, and evaporated to dryness in vacuo. The obtained 10.6 g of 73,91523 crude product is purified by chromatography on silica gel using a 4: 1 mixture of chloroform and ethyl acetate. 7.2 g of solid fraction are recrystallized from chloroform-ethyl acetate-hexane to give 3.0 g of a yellow solid, m.p. 187-188 ° C (dec.).

Analysis for the compound::

Calculated: C 46.72, H 2.35, N 10.90%

Found: C 46.96, H 2.60, N 9.77% Example 46 Preparation of 2,5-dichloro-3- (3,4-dichlorophenyl) -4-nitropyrrole

+ so2ci2-► LJ LI

c r ^ N ^^ ci

H H

20

To a mixture of 3- (3,4-dichlorophenyl) -4-nitropyrrole (2.5 g, 9.7 mmol) heated to about 40 ° C in 200 mL of chloroform is added 2.95 g per minute. (22 mmol) sulfuryl chloride. After a second hour, the mixture is diluted with 100 ml of saturated sodium hydrogen carbonate solution and 300 ml of ether. The organic layer is separated and dried over magnesium sulfate. Evaporation to dryness in vacuo left a brown solid which was chromatographed on silica gel using chloroform-ethyl acetate 4: 1. The orange solid fraction is recrystallized from chloroform and then rechromatographed on silica gel using chloroform-ethyl acetate 4: 1 to give 0.36 g of a yellow solid, 35 mp 19-194 ° C.

74 91523

By the method of Examples 45 and 46 above, 2,5-dichloro-3-nitro-4-phenylpyrrole is also prepared, mp 193-194 ° C (dec.).

Example 47 Preparation of 5- (p-chlorophenyl) pyrrole-2,4-dicarbonitrile

/ CN

10 \ OMF

A sample of 1'N + ciso2nco + (ch3) 2ncho - 15 ™ - 20 2-ε-chlorophenyl-3-cyanopyrrole prepared by the method of Example 4 (3.0 g, 0.015 mol) is dissolved in 50 ml of dry dimethoxyethane. To this solution is added chlorosulfonyl isocyanate (3.39 g, 0.024 mol). The addition is exothermic and some cooling is required. After stirring for 3 hours at room temperature, dimethylformamide (6-7ml) is added and the solution is stirred for a further 4 hours. The solution is then poured into water to precipitate a white solid (3.4 g, 100%). A sample of this (1.0 g) is purified by dissolving in ethyl acetate and then passing the solution through a 60 ml coarse filter funnel filled with silica gel. The filtrate is evaporated to dryness to give 0.7 g of a white solid, m.p. 235-240 ° C.

Following the procedure of Example 47, the following analogs are prepared: 91523 75

CN

rY

10 1-R L

3-Cl 4-Cl> 225 ° C

15 H 4-OCF 3 185-190 ° C

H 4-CF 3 180-185 ° C

Example 48 Preparation of 3-bromo-5- (p-chlorophenyl) pyrrole-2,4-dicarbonitrile A sample of 5- (E-chlorophenyl) pyrrole-2,4-dicarbonitrile (1.0 g, 0.004 mol) is dissolved. To 20 mL of dioxane is added and then a solution of bromine (0.8 g, 0.005 mol) in dioxane (10 mL) is added. The solution is stirred for several hours at room temperature and then poured into water to precipitate a white solid (1.2 g, 100%). The mp of the solid is> 225 ° C and the mass spectrum of sample 35 gives a pattern consistent with the desired structure.

76 9 1 5 2 3

Following the procedure set forth in Example 48 above, the following additional compounds are prepared:

n CN

Br \ / 10

E L Sp ° C

15

3-Cl 4-Cl> 250 ° C

H 4-OCF 3 218-223 ° C

H 4 ”CF 3 239-241 ° C

Example 49 20 Preparation of bromifumaronitrile

CN CN

- / Br2 / CHCl3 / ^ / / -> / - \ NC C-HBr) NC Br 25

Under a stream of nitrogen, fumaronitrile (15.6 g, 0.2 mol) is heated in CHCl 3 (150 mL) at reflux to give a clear solution. A solution of bromine (5.3 mL, 0.2 moles) in CHCl 3 (25 mL) is added dropwise over 30 minutes, resulting in slow color fading and the release of acidic (pH test paper) fumes. The solution is boiled for a further 90 minutes, during which time most of the color has disappeared. The solution is cooled and the solvent is removed in vacuo to leave a golden brown oil (weight approximately 91523 77 for bromofumaronitrile). the oil is treated by distillation from ball to ball (0.2 nunHg), keeping the temperature below 120 ° C (rapid decomposition of the substance occurs above this point). A semi-solid is obtained which slowly forms a waxy, golden brown solid, mp 43-47 ° C.

Analysis for C 1 H 2 HBrN:

Calculated: C 30.57, H 0.64, N 17.83%

Found: C 29.13, H 0.75, N 16.94% Example 50 Preparation of 2-phenyl-pyrrole-3,4-dicarbonitrile CN \ / s 15 + TnsA / Kln NC Br N N '

NC CN

20 HMPfl / 3 eq. .HP0 (-TMS, -HBr, -CH3SH)

A solution of bromofumaronitrile (4.7 g, 0.03 mol) and N- (trimethyl-25-silyl) methyl S-methylbenzenethioimidate (7.1 g, 0.03 mol) in hexamethylphosphoramide (HMPA) (protected by a stream of nitrogen) ( 35 ml), stirred at room temperature. Add water (1.6 mL, 0.09 mol) washed with HMPA (10 mL) in one portion. In solution, an exothermic reaction begins almost immediately as the temperature rapidly rises to 100 ° C before decomposing. The resulting dark red solution is stirred at ambient temperature for 20 hours. When the reaction mixture is poured into an ice / water mixture, a resinous substance is formed, which slowly forms a solid beige solid. This material is collected on a filter pad and washed with cold water and dried as a filter. After further drying (vacuum oven; 60 ° C), the material is recrystallized twice from C 2 H 2 Cl 2 (DARCO treatment) to give a white powder.

5 Analysis for C12H7N3:

Calculated: C 74.61, H 3.63, N 21.76%

Found: C 74.45, H 3.84, N 21.61%

Mp = 197-200 ° C.

Example 51 Preparation of 2-bromo-5-phenylpyrrole-3,4-dicarbonitrile

NC CN NC CN

15 H 2 Cl 2 / CHCl 3 / Br 2 Under a stream of nitrogen, 2-phenyl-pyrrole-3,4-dicarbonitrile (1.4 g, 0.0075 mol) is added to CHCl 3 (35 mL). ), which dissolves a lot of solids.

A solution of bromine (0.4 mL; 0.008 mol) in CHCl 3 (5 mL) is added dropwise over 20 minutes. Initially • 25 the color disappears quickly, but when a new, resinous solid begins to precipitate, the color is retained. After stirring for 30 minutes at ambient temperature, the mixture is heated to boiling, resulting in the formation of much more discrete solids. After boiling for 90 minutes, the reaction mixture is cooled and sampled and analyzed (HPLC), indicating that about 60% of the starting material is still present. Fresh bromine (0.2 ml; 0.004 mol) is added in one portion and boiling is continued for another 45 minutes, after which 35 samples show 10% starting material remaining. A second fresh portion of bromine (0.2 mL; 0.004 mol) is added to the boiling suspension and boiling is continued for another 30 minutes. The suspension is cooled and stirred for 18 hours at room temperature. The solvent is removed in vacuo to give a greenish solid which is extracted with hot CHCl 3 to leave a dark residue. The extract is treated according to DARCO and filtered hot. A white precipitate quickly begins to precipitate from the clear yellow filtrate. After cooling to -10 ° C, the white solid is collected by filtration.

Analysis for c2H6BrN3:

Calculated: C 52.94, H 2.21, N 15.44, Br 29.41%

Found: C 51.64, H 2.35, N 14.91, Br 28.69% mp = 225-258 ° C.

Example 52 Preparation of 2- (3,4-dichlorophenyl) -5-nitropyrrole-3-carbonitrile

CN CN

20 * HN ° 3 + flc2 ° - f / λ \ / 7 ~ \ h N // \\ - ci 2 HV 'y-ci \ i ci 25 2- (3,4-dichlorophenyl) pyrrole-3-carbonitrile ( 3.0 g, 0.013 mol) are added to acetic anhydride (50 ml) and 90% nitric acid (0.6 ml) with very weak exothermic reaction. The mixture is slowly warmed to 30 ° C and then maintained at 30-33 ° C until all is dissolved. Gradually a new solid precipitates. The mixture is stirred for 2-3 hours at room temperature and then poured into water and ice to decompose acetic anhydride. After stirring for 1 hour, the mixture is filtered and the solid (2.9 g, 82%) is collected and dried. An aliquot (1.5 g) is purified by column chromatography on silica gel, eluting with hexane / ethyl acetate 75/25 to give 0.7 g of a yellow solid, mp 228-231 ° C.

5 Analysis for C 1 H 2 Cl 2 N 2 O 2:

Calculated: C 46.80, H 1.77, N 14.89, Cl 25.17%

Found: C 46.50, H 1.96, N 14.27, Cl 24.30%

By the same procedure, starting from 2- (E-chlorophenyl) pyrrole-3-carbonitrile, 2- (E-chlorophenyl) -10 5-nitropyrrole-3-carbonitrile is obtained, mp 201-206 ° C. 2- (N-trifluoromethylphenyl) pyrrole-3-carbonitrile is also obtained from 2- (E-trifluoromethylphenyl) -5-nitropyrrole-3-carbonitrile by the method described above. The melting point of this compound is 164-165.5 ° C.

Example 53 Preparation of 4-bromo-2- (3,4-dichlorophenyl) -5-nitropyrrole-3-carbonitrile

CN Br \ CN

20 _ / dioxane \ _ / + Brs - * 02νΛΛ \ 02N ^ N ^ \ a— \ h V7 \ V C1 H V7 y — Cl

Cl ci 25 L1 2- (3,4-dichlorophenyl) -5-nitropyrrole-3-carbonitrile (0.5 g, 0.0017 mol) is dissolved in dry dioxane (10 mL). To this solution is added bromine (0.28 g, 0.0017 mol in dioxane. After stirring overnight, the solution is poured into water to precipitate a tan solid (0.54 g, 88%). Recrystallization from acetonitrile (5 mL) gives 0.26 g of a tan solid, m.p. 195-200 [deg.] C. Analysis for C18 H18 BrCl2 N2Cl2: 35 Calculated: C 36.57, H 1.10, N 11.63, Br 2213, Cl 19.67% Found: C 36.46, H 1.29, N 11.50, Br 21.63, Cl 19.28% 91523 81

Following the procedure of Example 53 above, but starting from 2- (p-chlorophenyl) -5-nitropyrrole-3-carbonitrile, 4-bromo-2- (E-chlorophenyl) -5-nitropyrrole-3-carbonitrile is obtained. mp 180-185 ° C.

Example 54 5- (3,4-Dichlorophenyl) -4-nitropyrrole-2-carbonitrile c / No 2 10 HNO 3 NC ΰ \ U - * \\

0C20 H

To a suspension of 5- (3,4-dichlorophenyl) -5-pyrrole-2-carbonitrile (1.2 g, 5.1 mmol) in 25 mL of acetic anhydride at 30 ° C under nitrogen is added dropwise 90%: nitric acid (0.3 mL, 5.1 mmol). The reaction mixture is exothermic to 45 ° C and turns to a green solution. After stirring for 2 hours, the reaction mixture is poured into 50 ml of water and stirred vigorously for 5 minutes. The beige precipitate formed is filtered off and dissolved in a minimum of acetone. Chromatography on silica gel using 3: 1 hexane-ethyl acetate gives nitropyrrole · 25 (1/2 g, 84%) as an off-white solid, mp> 200 ° C.

Example 55 3-Bromo-5- (3,4-dichlorophenyl) -4-nitropyrrole-2-carbonitrile 30, NO2 Br_. N02

Sr 35 To a suspension of 5- (3,4-dichlorophenyl) -4-nitropyrrole-2-carbonitrile (0.6 g, 2.1 mmol) in 10 mL of 82 91523 dioxane at 25 ° C under nitrogen is added dropwise addition of a solution of bromine (0.3 g, 2.1 mmol) in 5 mL of dioxane. The reaction mixture is stirred overnight. Upon addition of 50 mL of water, a yellow solid precipitate formed which was collected and dried in a vacuum oven 5 (50 mmHg, 45 ° C) to give brominated pyrrole (0.7g, 90%) as a pale yellow solid, mp> 200 ° C.

Example 56 4- (p-Chlorophenyl) -2- (trifluoromethyl-2-oxazolin-5-one) Trifluoroacetic anhydride (1.7 ml; 0.012 mol) is added in one portion to powdered 2- (p-chlorophenyl) glycine (11, 4 g, 0.06 mol) immediately causing an exothermic reaction to about 40 ° C, whereupon a yellow color forms on the surface of the solid.

15 When the mixture is slowly heated to 70 ° C, the solid dissolves further in the orange / golden brown oil. All solids dissolve in about 2 hours and heating is continued for another hour. The solvent is removed on a vacuum rotary evaporator. Toluene is added twice and removed in vacuo, but the odor of trifluoroacetic acid is still evident. This yellow semi-solid (theoretical yield; purity> 90% by HPLC) is the compound identified above and is used in the next step without further purification.

Example 57 Preparation of 2- (p-chlorophenyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile 4- (E-chlorophenyl) -2- (trifluoromethyl) -2-oxazolin-5-one (2.5 g) , 0.01 mol) is dissolved in nitromethane 30 (50 ml). 2-Chloroacrylonitrile (8.0 ml; 0.10 mol) is added in one portion to the solution and the resulting solution is stirred at reflux for 18 hours under a nitrogen atmosphere. On cooling the red-brown solution to -5 ° C in an ice-acetone bath, a precipitate forms which is collected by filtration and washed with a small amount of cold nitro-83 91523 methane. The resulting tan solid is recrystallized from hot ethylene chloride to give the product as white crystals (1.8 g, 56% of theory), mp 238-241 ° C (dec).

Using the appropriate arylglycine in the procedure of Example 55 and following the procedure of this example, the following 2-aryl-5- (trifluoromethyl) pyrrole-3-carbonitrile is prepared:

/ CN

10 _ /

CF

3 H U / 15

R L SP ° C

HH 215-218 H 4-CH 3 191-193 H 4-OCH, 168-180 (dec.) 20 3 3- Cl 4 -Cl 245-246 (dec.) H 4-CF 3 218-219 25 Example 58 4- Preparation of bromo-2- (p-chlorophenyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile Under a stream of nitrogen, 2- (p-chlorophenyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile (1.6 g, 0.005 mol) - 30 lia) suspension in acetic acid (25 ml) is heated, all substances dissolving into a clear solution at about 60 ° C.

A solution of bromine (0.8 ml, 0.015 mol) in acetic acid (10 ml) is added dropwise over 15 minutes to the boiling solution. The solution is boiled for 6 hours, then stirred for 18 hours at room temperature.

• · 84 91 523

HPLC of the reaction mixture shows about 80% conversion to product. The mixture is heated back to boiling and more bromine (0.5 ml; 0.01 mol) in acetic acid (5 ml) is added dropwise. After a further 3 hours of boiling, the sample shows> 95% conversion to the product.

The reaction mixture is cooled and the solvent is removed in vacuo on a rotary evaporator to give a dark gray solid. Toluene is added to the mixture and removed in vacuo, but the odor of acetic acid is still 10. The whole is dissolved in hot toluene (75 ml) to a cloudy solution which is treated with a DARCO filter and filtered. A white solid precipitates from the pale rose solution during cooling to ambient temperature. After cooling in the freezer 15, the solid is collected by filtration, washed with hexanes, and dried on a filter. Further drying in a vacuum oven at 45 ° C gives the product (1.2 g; about 60% of theory); mp 247-250 ° C (dec.).

Analysis for C ^ ^ B ^ IF ^^:

Calculated: C 41.20, H 1.43, N 8.01, Br 22.89, Cl 10.16, F 16.31%

Found: C 41.27, H 1-48, N 8.10, Br 22.92, Cl 10.16, F 16.03% 25 Bromination of the appropriate 2-aryl-5- (trifluoromethyl) pyrrole-3-carbonitrile obtained by the method of Example 57 according to the above procedure, the following additional examples are prepared:

II

91523 85

Β \ / CN

5 CF3 "W?

E L S.P. ° C

10 HH 235-238 H 4-CH3 244-245 3-C14-C1218-223 H4-CF3 225-226 15 Example 59 2- (4-chlorophenyl) -5-trifluoromethyl-pyrrole-3,4-dicarbonitrile manufacture 0

20 H2N \ Ä ° v \ n / = N

Y ^ OH —-0 f 1 / Vj N- XBr (CF3CO) 20 - * I 3 2, f | N f CH 3 NO 2 // 18h

'2h jU

: T

- 25 Cl

MH F

30 1! Y

: Cl

Trifluoroacetic anhydride (3.1 ml; 0.022 mol-35 mol) is added in one portion to 91523 (2.0 g; 0.011 mol) of (4-chlorophenyl) glycine, which immediately causes the formation of a yellow color and some boiling.

The mixture is heated slowly to boiling, causing all of the substance to dissolve into a yellow / orange solution which is further heated for 2 hours. The reaction mixture is cooled and the solvent is removed in vacuo. Toluene is added twice and removed in vacuo to give a very thick oil (VqQ = 1800 cm.

This residue is dissolved (slightly insoluble) in CH 3 NO 2 (40 mL) and bromofumaronitrile (2.7 g, 0.018 mol) is added in one portion. The resulting solution is heated at reflux for 18 hours to give a dark red solution. The solvent is removed in vacuo and the dark residue is dissolved in Cl 2 Cl 2, removing a small amount of Liu-15 non-lubricating material by filtration.

The material is fractionated by dry column chromatography (silica gel; 3% 2-propanol in CH 2 Cl 2) and the appropriate fractions are collected. Evaporation of one fraction to dryness gives the title compound as a yellow solid which is recrystallized from CH 2 Cl 2 (DARCO treatment) to give a pale yellow solid (0.2 g), mp = 238-241 ° C (some decomposition).

Example 60 • 25 p-Chloro-β-β (formylmethyl) amino] quinamitrile, diethyl acetal d 2 O 2 CH 2 O + Et 2 O 2 30 H \ 35 Magnetically stirred solution of 250.0 g (1.39 moles) of chlorobenzoylacetonitrile, 87,91523,203 mL (185.9 g, 1.39 moles) of 2,2-diethoxyethylamine, and 1300 mL of dry toluene, are heated at reflux for 20 hours. Water is collected in a Dean-Stark trap (23.8 ml, 95.2% of theory). A hot cloudy, dark brown solution with a large amount of insoluble solids is filtered through a diatomaceous earth filter device. After dilution with 200 ml of ethyl acetate, the solution is filtered through a column of silica gel, measuring 7 cm x 13.5 cm. The filtrate is evaporated to dryness in vacuo to give 10,354.3 g (crude product yield 86.4%) of a clear dark oil which slowly becomes a solid. This solid is recrystallized from hot cyclohexane to give 324.2 g (79.1% yield) of a waxy orange solid. NMR of this product shows it to be a mixture of 15β-chloro-N- (formylmethyl) amino] cinnamonitrile, diethyl acetal (Zj isomer (78%) and (E) isomer (23%), mp 60-72 ° C. The following analytical values are those of another similarly prepared sample.

Max (Mull, Nujoi): 3325 (s), 3065 (m), 2197 (s), 1600 (s), 20 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 = 8.6Hz, 2.12H, two aromatic protons), δ 7.37 (d, J = 8.6Hz, 2.12H, two * 25 aromatic proton), ^ 5.10 (E) & £ 4.86 (Zj ^ br t, 1.25H, one NH proton7, £ 4.69 (Z) & £> 4.60 (E) / t, J = 5.1 Hz, 1.05H, one methine proton on acetal carbon7, S 4.07 (E) & b 4.05 (Zj / s, 0.83H, enamine Jb proton ?, 3.71 (E) Δ 3.68 (Zj / q, J = 7.1 Hz, 2.22H, two methylene protons 30 in one of the two ethoxy groups7, by 3.56 (Zj & $ 3.53 (E) • / g, J = 7 , 1 Hz, 2.22H, two methylene protons in one of the two ethoxy groups7, S 3.18 (t, J = 5.1 Hz, 1.77H, two methylene protons in the ethylene acetal group), £ 1.20 (t, J = 7.1 Hz, 4.90H, six methyl protons of two ethoxy groups).

t · V

88 9 1 5 2 3 C-NMR (chloroform): δ 161.21 (α-enamine-carbon), 136.29 (Z) & 134.60 (E) 1-ylyl ring with either Cl or C-47, £ 134 .08 (Z) & b 132.30 (E) phenyl ring either Cl or C-47 / S 129.34 (ZJ & b 129.89 (E) / phenyl ring 5 either C-2.6 or C -3.5 ?, £ 12 8.94 (Z ^) & b 128.63 (E) Ajoko phenyl ring C-2.6 or C-3.57, £ 121.19 (_Z) & £ 119, 50 (E) / nitrile carbon7, £ 99.43 (_Z), & £ 100.63 (E) Γ / 3-enamine carbon?, £ 6188 (Z) & £ 63.25 (E) / _ acetal methine carbon7, b 62.64 (^) 63.03 (E) / methylene carbons of the ethoxy groups?, 10 £ 46.32 (Zj & ^ 47.33 (E) / methylene carbon of the ethylamine group?, £ 15 .26 (methyl carbons of ethoxy groups).

Microanalysis (mp 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% Following the above procedure but substituting the appropriate benzoylacetylacetonitrile for E-chlorobenzoylacetonitrile and / or 2,2-diethoxyethylamine with the appropriate 2.2- with di (C 1-4 alkoxy) ethylamine, the following compounds are obtained: 89 91523 / p 'S-CO-CH 2 CN + H 2 NCH 2 CH (C 1 -C 4 "alkoxy) 2 s \ -4- / toluene" i' | 'N-CH 2 CH (C 1 -C 4 alkoxy) 2

R H

10, "" -alkoxy)., Sp o_

L M R fC1-C4. 2 2 ___C

H H E-CH3OCO (OC2H5) 2 68-73 15 H E-CH3 H (OC2H5) 2 59-69 H τη-OCH. e-OCH_ (OC-H-), red-orange half- 3 3 s solid H _ _ (OC2H5) 2 62-70 20 E-Cl HH (OCH3) 2 --- H E-CH3 H (OCH3) 2 --- Η τη-Cl E-Cl (OC2H5) 2 --- HH E-OCF3 (OC2H5) 2 HH E-CF (OCX) 25 91523

Example 61 2- (p-Chlorophenyl) -pyrrole-3-carbonitrile

.cn

To 10 108 ml of trifluoroacetic acid stirred at 23 ° C are added 54.00 g (0.183 moles) of solid ε-chloro-chloro-acetic acid. 6- (formylmethyl) amino / cinnamonitrile, diethyl acetal over 45 minutes. This addition exothermically raises the temperature to 38 ° C and 32 minutes after the addition, a solid began to precipitate. After stirring for 30 minutes at room temperature, the reaction mixture is filtered under vacuum and the collected solid is washed first with trifluoroacetic acid, secondly with ethyl acetate-hexane, and finally with hexane. Saan-20 to is 16.83 g (45.4%) of an off-white solid, mp 165-166 ° C. The following analytical values are obtained from a similarly prepared sample.

Me * (Mull, Nujol): 3275 (brs), 2225 (s), 1502 (s), 1410 (m), 1275 (a), 1200 (m), 1108 (s), 1023 (a), 999 ( a), 908 (m), 25,843 (s), 752 (s), 722 (s), 695 (s), 620 (s) Cm ”1.

1 H-NMR (acetone): δ 11.22 (v br s, 0.99H, one pyrrole NH proton), δ 7.82 (d, J = 8.9Hz, 2.46H, two aromatic phenyl protons), S 7.51 (d, J = 8.9Hz, 2.46Hz, two aromatic phenyl protons), $ 7.02 (t, J = 2.6Hz, 1.01J, one pyrrole proton at C-5 ), S 6.58 (t, J = 2.6 Hz, 0.77H, one pyrrole proton at C-4).

C-NMR (acetone): $ 137.73 (pyrrole C-2), h 134.42 (E-chlorophenyl for C-4), - $ 129.93 (methine carbons for phenyl ring C-3.5), % 128.07 (methine carbons at 35 phenyl ring C-2.6), S 121.21 (pyrrole at C-5), $ 117.93 (nitrile carbon), $ 113.78 (pyrrole at 91523 91 carbon C-4), 90.86 (pyrrole carbon for C-3).

Microanalysis (mp 202.64):

Calculated: C, 65.19%; H, 3f48%; N, 13.83%; Cl, 17.50% Found: C, 64.18%; H, 3.52%; N, 13.63%; Cl, 17.74% Using the above procedure or replacing trifluoroacetic acid with concentrated hydrochloric acid, the following compounds are obtained:

CN

10 _ / 15 M and / or R Spoc Acid used

4-C1 165-166 cone. HCl, CF 3 COOH

3.4- di-Cl 216-221 CF3C00H

2- C1 156-157 CF3COOH

20 4-OCF3 143-145 CF3COOH

4-CF 3 179-180 CF 3 COOH

2.4- di-Cl 197-199 CF3COOH

3- Cl 150-156 CF 3 COOH

4- CN 210-212 CF3COOH

25 4-F 167-170 cone. HC1

4-SO 2 CH 3 221-221.5 CF 3 COOH

3.4- di-F 173-175.5 CF 3 COOH

3- CF3 166-168 CF3COOH

4- COOCH3 155.5-158 CF 2 COOH

3Q 4-CH3 117-137 CF3COOH

4-NO2 174-177 CF3COOH

92 91523

Example 62 4,5-Dichloro-2- (p-chlorophenyl) pyrrole-3-carbonitrile

CN ci? N

jj ^ 2.2 eq-SOgClg jj ^ HORc η1 '/ ^ Ν / \ / = Γ \ __ Γΐ H V /> - Cl C1 H \ J / 10

To a mechanically stirred solution of 16.83 g (83.1 mmol) of 2- (E-chlorophenyl) pyrrole-3-carbonitrile in 450 ml of glacial acetic acid at 36 ° C is added dropwise over 18 minutes 14.7 ml (24 , 70g, 183.0 mmol) sulfuryl chloride. The addition causes a slight exotherm to 39 ° C and after a further 16 minutes the reaction mixture is filtered under vacuum. The collected solids are washed first with acetic acid and then with water. This solid melts after recrystallization from hot ethyl acetate at 259-261 ° C. Other samples of this product were prepared by similar methods and the analytical values for one such product are shown below.

MftX (Mull, Nujol): 3170 (brs), 3100 (m), 2225 (s), 1508 (m), 25 1097 (m), 825 (s), 717 (m), 660 (m) cm-1 .

1 H-NMR (DMSO): δ 7.72 (d, J = 8.8Hz, 2.0OH, two aromatic protons), 7.56 (d, J = 8.6Hz, 2.0OH, two aromatic protons) ).

C-NMR (DMSO): £ 136.01 (pyrrole-C-2-carbon), £ 133.92 (E-chlorophenyl-C-4 carbon), £ 129.09 (E-chlorophenyl, C-3, 5 carbons), >> 127.41 (E-chlorophenyl C-4 carbon), £ 127.11 (E-chlorophenyl Cl-carbon), £ 114.49 (nitrile-1-carbon), £ 114.10 (pyrrole C -5 carbon), £ 110.92 (pyrrole-C-4 carbon), £ 90.09 (pyrrole-C-3 carbon).

35 Microanalysis (mp 271.54):

Calculated: Cf 48.65%, H, 1.86%; N, 10.32%; Cl, 39.17%

Found: C, 49.22%; H, 2.12%; N, 9.85%; Cl, 39.03% 91523 93

Example 63 4,5-Dibromo-2- (pC, α, N, N-trifluoro-p-tolyl) -pyrrole-3-tolyl) -pyrrole-3-carbonitrile

5 CN Br CN

+ Br2 --- iSN ^ CP3 * H \ j - “* 10

To a stirred mixture of 0.8 g of 2 - (- [±, 6,0-trifluoro-p-tolyl) -pyrrole-3-carbonitrile in 70 ml of chloroform is added 2 ml of bromine. Upon stirring overnight, a white solid precipitates which is collected by filtration. The thin layer chromatography plate (ethyl acetate-hexane 1: 1) shows a single component; mp> 230 ° C.

Analysis for ci2H5Br2F3N2:

Calculated: C 36.55, H 1.27, N 7.11, Br 40.61% Found: C 36.40, H 1.08, N 6.99, Br 40.55%

Following the above procedure, but substituting appropriately substituted phenylpropyl-3-carbonitrile for 2- (<, N, 06-trifluoro-p-tolyl) pyrrole-3-carbonitrile, the following compounds are obtained.

25

X CN

94 91523 li ME Σ XS,? Lc HH 4-NO2 Br Br 274-277 HH 4-F Cl Cl> 220 5 HH 4-F Br Br> 220 HH 4-SO2CH3 Cl Cl> 230 H 3-F 4-F Cl Cl> 230 H 3-F 4-F Br Br> 220 2-C1 3-Cl 4-Cl Cl Cl 10 2-Br 3-Br 4-Br Br Br HH 4-OCF3 Cl Cl 222-225 HH 4- OCF3 Br Br

H H 4-OCF3 Cl H

H H 4-CN Br Br> 230. c H H 4-CN Cl Cl> 240

Id HH 4 -SO 2 CH 3 Br Br> 230 HH 4 -NO 2 Cl Cl 246-249 H 3-Cl 4-Cl Br Br> 260 HH 3-CF 3 Cl Cl> 230 2Q HH 4-COCH 3 Cl Cl 251-254 H 2, 3-CH = CH- Cl Cl 244-247 HH 4-CH3 Cl Cl 215-217 H 2-Cl 4-Cl Br Br> 230 HH 3-Cl Cl Cl> 230 H 2-Cl 4-Cl Cl Cl> 230

L · D

HH 4-Cl Br Br 273-274 HH 2-Cl Br Br> 230 HH 4-CF3 Cl Cl> 230 HH 4-Br Cl Cl> 235 HH 2-Cl Cl Cl> 230 30 H 3-Cl 4-Cl Cl Cl> 235 HHH Cl Cl 254-255

II

91 523 95

Example 64 o6- (2,2-Diethoxyethylamino) - [3-nitrostyrene and 3-nitro-2-phenylpyrrole (HtNCH.CH1OEl), - (N-C-CH-NO, -Y '-' nh- chj ch (oe t) jh ού-nitroacetophenone (5.7 g, 0.0345 mol) is dissolved in 100 ml of antholuene and 4.6 g (0.0345 mol) of aminoacetaldehyde diethyl acetal are added. The reagents are placed in a 250 ml round-bottomed flask fitted with a Dean-Stark trap. The trap is filled with a 4A molecular sieve and the mixture is heated at reflux for 18 hours. The toluene is removed in vacuo to give 8.36 g of σε- (2,2-diethoxyethylamino) -β-nitrostyrene as a brown oil.

To this oil is added 50 mL of concentrated HCl. As the bottle is swirled, the oil turns into a yellow suspension. After 10 minutes, the solid is filtered off to give 2.48 g of a yellow solid. Recrystallization from ether / ethyl acetate / hexane gives the product in two fractions, 2.08 g, mp 190-192 ° C, (31%).

Max 1485 cm-1 (NO 2), 1 H-NMR (CDCl 3) DMSO) δ 6.73 (m, 2H), δ 7.46 (m, 5H).

According to the above reaction, other β-nitrostyrene compounds can be prepared by replacing o-nitroacetophenone with an appropriately substituted o-nitroacetone and / or aminoacetaldehyde diethyl acetal with 2,2-di (C 1-4 alkoxy). with ethylamine to give the following compounds: 96 91523 ^ -CCHgNOg + HgNCHgCH (C1-C4-alkoxy) -2 ^ toluene

5 R

Li £> T "" · —1 γ \ ^ - Ζ- 'N-CH2CH (C1-C4-alkoxy) 2

R H

10 1 HB (C1-4 alkoxy) 2 HH E-CH3OCO (OC2H5) 2 15 H E-CH3 H (° c2h5) 2 H ffi-OCH3 2-0CH3 (OC2H5) 2 8 - - <0C2H5> 2 20 E -Cl HH (OCH3) 2 h e-ch3 h (och3) 2 HH E-CF3 (0¾¾) 2

Example 65 3 ς 3 2,3-Dichloro-4-nitro-5-phenylpyrrole NOg Cl NOg 30 0 ^ ^ ^ + NaOCl - * ^

A mixture of 3-nitro-2-phenylpyrrole (1.56 g, 0.0083 mol) in 60 ml of dioxane is cooled in an ice bath.

i I

97 91 523 in tea by dropwise addition of 25.9 g (0.0182 mol) of technical grade sodium hypochlorite. After stirring for 45 minutes, the mixture is acidified with concentrated HCl. Add water and ethyl ether. The layers are separated and the supernatant is washed with H 2 O, dried over anhydrous MgSO 4 and evaporated to dryness in vacuo to give 2.21 g of a yellow solid. Purification by chromatography, using silica gel and eluting in increasing proportions with wool in ethyl acetate / hexane gives, after evaporation to dryness, 0.77 g of a yellow solid (36%), mp 190-190.5 ° C;

Analysis for C 18 H 18 S 2 C 2 Cl 2;

Calculated: C 46.72, H 2.35, N 10.90% Found: C 46.96, H 2.86, N 10.02%

Example 66

Estimates as insecticides and acaricides All experiments have been performed using technical materials. All concentrations reported herein are concentrations of the active ingredient. All experiments have been performed at 27 ° C.

Spodoptera eridania, third stage larvae, "southern armyworm"

Pretty mucus bean leaf, developed 7-8 cm; 25 in length, immerse in the test suspension by mixing 3 of it and place in a dry cover. The leaf is then placed in a 100 x 10 mm petri dish with moist filter paper at the bottom and ten third-stage per-host larvae. The dish is stored for 5 days before 30 observations are made of mortality, reduced nutrition, or any disturbance associated with normal bark replacement.

Spodoptera eridania, 7-day residue Plants treated in the 35 tests mentioned above are kept under high-intensity lamps 98 91 523 in a greenhouse for 7 days. These lamps double the effect of a bright sunny June day in New Jersey and illuminate for 14 hours during the day. After 7 days, the leaves are sampled 5 and analyzed as in the above experiment.

Aphis fabae, mixed stage, bean leaf litter In pots with individual nectar plants (Tropaeolum sp), about 5 cm in size, about 100-200 leaf leaves are planted the day before the experiment. For each 10-month period, the test mixture is sprayed over 2 cycles at 4 rpm on a rotating table in a cover, using 154 DeVilbiss nebulizers. The tip of the shower is kept at a distance of about 15 cm from the plant and the shower is oriented so that the plants and leaf lice can be completely coated. The sprayed pots are placed on their sides on white enamel trays and thus kept for 2 days, after which mortality estimates are performed.

Tetranychus urticae (P-resistant species), 2-spotted spider mite.

20 Select Pretty mucus bean plants, the first leaves of which have grown to a length of 7-8 cm, and cut one plant per pot. A small piece of the leaf taken from the main community is cut and placed on each leaf of the test plants. This is done about 2 hours before the 25 treatments to allow the mites to migrate to the test plant and lay their eggs. The size of the cut piece is varied so that about 100 mites are obtained for each leaf. At the time of treatment, the piece of leaf used to move the mites is removed and discarded. Plants infected with tick 30 are immersed in the test mixture for 3 seconds using agitation and allowed to dry in a cover. Plants are thus kept for 2 days before fully developed mortality estimates are performed using the first leaf. The second leaf is kept on the plant for another 5 days 35 before observations are made of the destruction of eggs and / or newborn nymphs.

99 91523

Diabrotic undecimpunctata howardi, third stage southern corn rootworm 3

One cm of fine talc is placed in a 30 ml wide-mouth screw-cap glass container. Pipette 1 to 5 ml of a suitable acetone suspension into the talc to give 1.25 and 0.25 mg of active ingredient per vessel. The vessels are kept under a gentle stream of air until the acetone has evaporated. The dried talc is fluffed, 1 cm 2 of ground seeds are added to feed the insects and 25 ml of moist soil is added to each dish. The vessel is covered with a lid and the contents are thoroughly mixed with a Vortex-Mixer. The ten third-stage rootworm is then added to each vessel and the vessels are loosely covered with a lid to allow air exchange for the larvae. 15 Treated containers should be stored for 6 days prior to performance calculations. Missing larvae are presumed dead because they disperse rapidly and cannot be found. The concentrations used in this experiment correspond to approximately 50, and 10 kg / ha, respectively.

20 Rating scale: 0 = no effect 5 = 56-65% dead 1 = 10-25% dead 6 = 66-75% dead 2 = 26-35% dead 7 = 76-85% dead 3 = 36-45% dead 8 = 86-99% dead 25 4 = 46-55% dead 9 = 100% dead R - reduced nutrition • · 100 91 523 cd sx

Oi ^ LO Γ- U Cn o o LO Mi un un O Γ 'O O 00 Ή in λ; Ο Mi MCE o • DO. o o o o en o oo σ \ &, O O ro

»O

: cd>

-B

: <D

O

r- en en en o> E o m O O * en O x oo en en en en en en

E

m 0 s> 1 o E o M otnencncncncnen

eC 'M

.e CU 4-1 r — i · Η 3: rd 0,4-1 £ O O O O LO o o o rd -H o o O 4-1 O '—I ["

Il o • HO I I 5-4

I -H M X I I -H I I O - ~ J M

• H -H O M -Hl -Hlr-IO m Xl C>,

pH -H O rd T3 -H M -H -H O I - M -O

Do * H i — I Mi I> —I 4—1 · —I * H p — I CO ^ 3 * Cd ^ 9 -— '

>, M Mi I rro -> i M Mi I -Mi li -H

C 4-> I PO »M I>, 4-1 I -H ^ I - r-ι -H

'—I CD -H O 1 PÖH OC-HOp-H -H PO -, - >> ,, - 1

M-l e '- -rH - Lo \ dl C' —'O PHI> 1-H

0 I 0 I pH I o-H I 4-1 o IM> 1-H I i — I -r-1

Mi pui X rs) O pj-h rg 4>, .H c \ i O M

Mi | H I M I -H -H I -H M I> 1-H C O I4-14-) C -pH rd -H M * H rH -pH -H Cn cd Ή ΟΉ CU H · Η I · ρ- |

pH M Mi M> 1 Μ> ίΜ HMiMi Ml -H 4-iH MOC

'C OIOO 0> ι4-) 00Ι0— ~ · Η · Η>, 010

.. id O ro OI 0C-H04-> P00-HMEO O -H XI

E-1 p — I I p — I -—- -H i — I 0 e p — I (D I p — 1'— 14-1 O Ή · Η i — IMM

CD Mi -H Mi-Η, Η ϋ MO Mi 6 H Mi>, - HMM> H Mi O td 4-1 -H i — I -H pH * H * H -HX * H · Η rH * H Do CXO Ή Ή D Mi en x) 0 Ό> ι-Η ΌΜΜ ΌΜΟ Ό GOIO -h χ) hi • H IM I> i M * O (Ö I0M I 0 XO Ή M | 44po Ό and M uoc-H and O Mi un DM in 4-ih - m: -U in-hi X · * C> i ·· CD Ή - p — I | - i — I Do - -H Cd 1 · Η -H - H Ή

> i -s-O'S’UHC ^ Mi m ίτ 4-1 O 9jp m M oj Ό C * 3 "4-i H

ιοί 91523 td S s: «^ m u en o co ^ lo o ez> en o o o o co n-

D

en ai <0 ϋ D e £ o en • C a o C4 D Dj m o o en o o oo r- o: tfl: <fl>

B

: <d tn tn en en en en

Di Γ "ε o

Dj O

ma h entn en en en en en en ε

D

0 s

> i O

ε o d o <5 h en en en en en en en en tn 102 91523 2 Λ PS \ ΓΟ υ & Ο m M Ln ο ο οο οο • Η C0 Λί ω α; ρ c ε o m • 3 α ο

OiQjQjroo ο οο: <d: «> • Η ΟΙ (<ι <Τι ΟΛ α r- Ε ο

Ch Ο ιο d ι — ι σ σ σ σ ε Ρ Ο

S

> ι Ο ε ο <σ ι — ι σ σ σ σ ι • Η -Ρ ω r- (3-Ρ & ι · η ε o ro Π5: ιβ 04 ο - Ρ4 4-> (¾ rP Ο ο οο οο ιϋ Ο

X

4-> I

3 I · Ρ ι-Ί II ο 1-1 - Ο 'O' I I Μ Ο 1-1 '' Τ -—- 4-> ρ Μ -Ρ 00 I -Η · Η H -rl

Η · Η -—. ι — I C Ρ ι — I

OG <Η I · Ρ> 1 II · Η Ο Μ ΙΟ 1-0 —I> ιΠ Ρ 1-ι ^ 'TP I> ι Cl I -Ρ Ρ 3 I Ρ -Η> ι · Η <1) -Ρ -Ρ · Η I> ι,> -1 -P> iPCrHlPPrPp-Ja, 3 εΟ, ΟΟΟ-ΗΟΟ 0 C ~: 3 ο · η own εορ ο —ρ

Ε-ι Ρ Ή t — I -Η Ρ Ο 1 — ΙΡι — I -s? <-I

αΐ £! >, Ρί Ρ>, Ρ Λί>, X C>, 4-4 -Ρ> 1 -Ρ Ο £ Χ XI -H di -Ρ '> ι 01 Ό C Τ3 O O I 03 Ο Ό -n? Ή -Ρ 10 I ι — I Ρ ft I Ρ ιί'ο Ό οο 4-4 ΠΛί-Ρ - LT) -Ρ 00-4-1 -C - I - -Ρ · Ρ I - -Ρ '11> 4 ΟΜίη <Ν Ό C (Ν "! Τ c ONLOCLi 91523

Example 67

Reviews as insecticides

Heliothis virescens, a third-stage tobacco bud worm. The cotton cotyledons are soaked in the test mixture and allowed to dry under cover. After drying, each is cut into four parts and the ten parts are individually placed in 30 ml plastic medicine cups with a 5.7 mm long piece of moist tooth. One third stage butterfly larva is added to each dish and a cardboard lid is placed on top of the dish. Treatment is maintained for 3 days before mortality calculations and estimates of reduction in feeding damage are made.

Empoasca abrupta, fully developed, western mashed potato leaf 15 A beautiful mucus bean leaf, about 5 cm long, is immersed in the test mixture with stirring for 3 seconds and placed in a cover to dry. Place the leaf in a 100 x 10 mm petri dish with moist filter paper at the bottom. Approximately 10 adult birches are added to each plate and treatments are stored for 3 days prior to performing the mortality count.

Blattella germanica, bait test, adult German Tor akka male 0.1% bait is prepared by pipetting 1 ml · '. A 1000 ppm concentrated acetone solution of 25 test compounds per gram of maize flour in a 30 ml wide-mouthed flask. The bait is dried by introducing a gentle stream of air into the flask. The bait is placed in a one-pint wide-mouthed Mason container and ten adult cockroach males are added. A lid is placed on top of the container 30 and a small piece of cotton dipped in 10% honey is placed on the lid. Mortality calculations are performed after 3 days.

Blattela germanica, residual test, adult German cockroach male 35 One milliliter of a 1000 ppm concentrated acetone solution of the test substance is slowly pipetted into the bottom of a 150 x 15 mm petri dish 104 91523 so that the coverage is as even as possible. After the precipitate has dried, 10 adult male larvae are placed in each dish and a lid is added. Mortality calculations are performed after 3 days.

5 Spodoptera eridania, systemic absorption, third stage larvae, "southern armyworm"

The compound is mixed into an emulsion containing 0.1 g of test substance, 0.2 g of Emulphor EL-620 ® emulsifier, 10 ml of acetone and 90 ml of water. This is diluted 10-fold with 10 ml of water to give a 100 ppm emulsion for the experiment. Thereafter, make 10-fold dilutions with water, if necessary. Pretty mucus bean plants, the first leaves of which have grown to a length of 7-8 cm, are cut across at least 3 cm above the ground 15 in order to avoid the introduction of soil bacteria, which causes stem spoilage during the experiment. The cut stems are placed in test emulsions and a piece of cotton is wrapped in each stem to keep the stem off the bottom of the bottle and to limit evaporation and evaporation of the compound. The experimental treatment is maintained for 3 days at 27 ° C to allow the compounds to be absorbed into the plant. One leaf is then taken from the plant and placed in a 100 x 10 mm petri dish with 10 southern armyworm as described in Experiment III. Mortality counts 25 and observations of feeding damage are performed 3 and 5 days later.

Empoasca abrupta, adult, western potato leaf piles, systemic absorption

The compound is mixed into an emulsion containing 0.1 g of test substance, 0.2 g of Emulphor EL-620 ® emulsifier, 10 ml of acetone and 90 ml of water. This is diluted 10-fold with water to give a 100 ppm emulsion for the experiment. Subsequent 10-fold dilutions are made with water as needed. Pretty mucus-bean plants, the first 35 leaves of which have grown to a length of 7-8 cm, are cut across at least 3 cm above the ground in order to

II

105 91523 avoid contamination by soil bacteria which causes stem contamination during the test. The truncated stems are placed in test emulsions and a piece of cotton is wrapped in each stem to hold the stem off the bottom of the 5 bottles and to limit evaporation and evaporation of the compound. The experiment is continued for 3 days at 27 ° C to allow the compounds to be absorbed into the plant. One leaf is then taken from the plant and placed in a 100 x 10 mm petri dish and tested as in Experiment VIII above.

For the above experiments, the classification scale is the same as described in Example 9.

106 91 523

O

O

o * —I

«G ΟΓ'Γ'-αοοοσιΟ QJ d« d (0

M O

M o

fti -H O

M -P rH

9 r- o o r- ~ o o o o o

-P .0 E

•> 1 d CO CO a c CL)

G I O

• h en m o E (ti ¢) i — i ai In a! E 1 ° ° w ° 1 m ° -P fti O CL, tn m e a.

> 1 tn i

CO S E O

° 01 ^ m 1 1 ^ Π2 E o ^ P3 21 ° 00 σ \ en o σι en o

E-t d-H

o o (^ co en en en en en

tn M

«A) Λί Cu tn d E o / 5, 2 o o o en o o en o X S VJ4

107 91 52 S

o o o

I-I

idE o en o o cd • p 'en tn o <L) Dj 05 Dj td M o

M O

(d -H O

DJ-) rj 0 +) o o o o o o en o o

J-): 0 E

• Dj en en a e

<D

C I o

• H en d o E <ei <l) r-H

OJ-VOj o en o o o en o o o

a) tn Dj E

JJ (0 O Dj W «K Dj> 1 en en SE o 1 <Dj o III l | oo en o en U en Dj» h ro SB o CQ Dj o σ> «n en o en co ao eo o H Dj Ή o in mo - - o enenen tn en tn oo cd

I H

en D td a) M Dj in tn Dj g o ed O Dj o o en o o o o o o o o

t * 5 S3 Dj I — I

<d o I 1 M III -Hl -Hl

+ J -rl o -rj I DO D -H -H -H

rrt DX! H -rl I II ΟΧ! O Ή D H I

-r-, O D - I -H Ό -P -H -H O D I O O O O m

Old ^ -P I -H TdrH iP ed O i — I D O D I

H Λ -H D "3 · O IO MM D Ai D P D O

H ^ I -> f— | 4-) ^ D D II J-) I ^ P

H | rn> ι · Ρ es D -D Ero -H DjDjIDjJJ

DjI ip G> 1 e \ l> i - I C -H 1 'O Dj O "H

O -—- -, - t -—- .— | O I Dj-η “Dj-η I * H I Ή ID'— 'D C

M | H I O A {N j "·» Ή I —— P (N H Tj-OinJ-> IJJ | -H

Ai CN O (N 4-> D I -P -P CS -P -P I O ID I Ή in -D Ί1 P

«Id I D I I td P» H Ή I r — I * H Ή D Ή D * P G ID 10

Ή -H D -H DjA5 D> i D -H> i D DD D> i Dl -Hl -P D

G E iP Eli 0iPJ-> E: pJ-> 0> i ODjO ^ -E ^ ED

td ODj O -P ro O G -P O G -P O Dj O-H OI OI O iP

E-I Dl -—- - * H D D I -HOG DOC P · - Ή Ή Ή Ή.— D -. DDj X) · Ρ Ρ Χ! 0 · Η ϋΉ Ο .ΟΡΟ Α! · Ρ Ρ Α! ΪΡ Αί · Ρ Χ3 -Ρ X! · Ρ • Η ι — I -H -H G Ή · Ρ -Η Λ -Η · Η X! -Ρ ι — I Ρ · Η> ι -rl Η · Η Η Ή Η Ό> 1 · Η ΌΡΟ ODD ODD Ό ΪρΡ Ό G d> ι fl> ι d> ι l> iD I MJ D lOtd IO d I> iD ΙΟ I £ p I ΪΡ I ΪΡ

inGJ-1 in P D li) O X in O A5 inGJ-> ro P RoG RoG RoG

*. fl) P - D> 1 ι — I I ι — I I * Q) P - I - O Q)

^ in G TfjJDj ^ Xiro p Ai ro Ι · P G es in tj D es P es P

108 91523 o o o

I-i

co E σ \ cr σι 0) a «dl cö

Ai O

AC O

CO-H O

d 4-> -H

0 4-> O O O

4-1: o e •>, d σι co Cu c ai

Cl o.

• H (I) ho E co Φ i — I

11 AC dl CT CT CT

cu en a. E

-M CO O d, CO «K di> 1 co

CO S E O

I <diO CT CT (Ti

CJ CO dH

LO

3: E o CO d o CT co oo

£ - (d> —I

o o

o CT CT CT

I.-I

CO d co <u M d CO d E o

CO O do (T CO CT

i * C X d i — I

- I

. CO o O O -1-4

AC rH i — I

4-> AC O I -H | co -h h m h in

• or T3 h - 0 I I

~ I>, -a · d 0 d

• 'T d I d d I

1-1 'O -> 1 4-4 -H

M CO d -H d -H d

_ 4-) I — I 0 G O

O I -H>, d I 3 —I

(40 CO £> i 4J * 3 * r — i r — I

I I e -H I 4-4 p

3 -1-4 XT (U c -H -H M

* ^ d I 4-1 | d d d 3 O —-- Hm 0 4-i> 1 g O -H E I O I d

c-1 —I r-4 O -H I O

AC> 1 S-ι (-1 AC C -H

Ή -Q 0 Ή - i — I

Ό C I 0 T3> e> 1 I <U d i — I I -> 1

CO 4-4 AC n ^ —I

'• H | -H 'Ά O

(N h (N O Cl 4-J

109 9 1 5 2 3

Example 68 A) Evaluation of test compounds as nematicides

Culture maintenance: C.elegans cultures (Bristol species, 5 J. Lewis) are stored in E. coli media on NG Agar Plates at 20 ° C. New crops are acquired weekly.

The nematodes to be tested are washed from 4-5 day old cultures using Fresh Ascaris Ringers Solution (FARS). The worms are further washed with FARS containing gentamicin to reduce bacterial contamination and centrifuged to separate the worms from the wash solution. This procedure is repeated three times. The washed worms are then added to C. bringgsae Maintenance Medium (CbMM), a preparation of GIBCOat supplemented with gentamicin (600 units / ml) and mycostatin (0.5 mg / ml).

The experiments are then performed on mixtures of the three compounds taken from another large-scale selection program to reduce additional work and compound costs.

The compounds are dissolved in acetone and made up to volume with an equal volume of water. The final test concentration of each compound in the mixture is 150 ppm. The test material is micropipetted (25 μl) into one well of a 96-well sterile tissue culture plate b, 25 (COSTAR) and the solvent is allowed to evaporate. These "hand-held" plates are used immediately or stored in a refrigeration unit without adverse effects on the compounds.

A freshly prepared volume (50 μg) of 30 C. elegans in CbMM is micropipetted into each hand. well and several control wells per plate. The culture plate is incubated at 20 ° C. Observations of efficacy are made under an analysis microscope at 4, 24, and 48 hours after immersion. Immediately before the interpretation of the plate, it is tapped lightly to stimulate the movement of the worms. Activity is judged no. 91523 individually, but semi-quantitatively, based on the effects of the herb on adult and larval mobility. The criteria are as follows: 8 = no mobility, 7 = significantly reduced mobility in about 5 95% of worms, 6 = reduced mobility, 5 = slightly reduced mobility, 0 = normal mobility, same as controls. Other factors indicative of activity are readily detectable, such as death, pelvic stiffness, shrinkage, twisting, paralysis, abnormal jerking, reduction in worm polylation in 48 hours, and other abnormalities in normal behavior.

Method for Caenorhabditis elegans test Day O - Planting E.coli-NG agar plate with 30-50 C.elegans 15 - Incubation at 20 ° C Day 4 - Harvesting a new C.elegens population - Washing with antibiotics - Transfer CbMM - Addition of C.elegans (25-100, ul) to the wells treated with "herbs" - Activity check 4 hours after immersion Day 5 - Activity check Day 6 - Activity check 25 a)

The herb-treated wells may be freshly or previously prepared and stored in a refrigerator.

The values obtained in these experiments are shown in Table III below.

30 B) Root-knot nematode test * Root-knot nematode populations (Meloidogyne incognita) are stored in fireball tomatoes in a greenhouse. Egg clusters are removed from contaminated root surfaces and kept on moistened filter paper for 24 hours to allow them to be buried. The larvae form U1 91523 and drip into the water below the paper. The test larvae are transferred to wells of the cell plate containing test compounds at concentrations of 300 ppm in 3% acetone, about 10 larvae per well of the cell. Lois-5 infected wells are maintained at 27 ° C and mortality is determined 24 hours after treatment.

The values obtained are shown in Table III below.

Table III

10 C.Ele. Root-knot 150 ppm nematodes LA 300 ppm 4,5-dichloro-2- [p- (trifluoromethoxy) phenyl] pyrrole-3-carbonitrile-4,4,5-dichloro-2- (6,6-trifluoro) -g-tolyl) -pyrrole-3-carbonitrile 99 5 4,5-Dibromo-2- (X, oC, o {, - trifluoro-g-tolyl) -20-pyrrole-3-carbonitrile 99 0 2.3- dichloro-4-nitro-5-phenylpyrrole 00 9 2,3-dichloro-5- (p-chlorophenyl) -4-nitro-pyrrole 99 9 2.3-dichloro-5- (3,4-dichlorophenyl) -4-nitropyrrole 99 0 2- (p-Bromophenyl) -4,5-dichloro-3-nitropyrrole 99 6 30 2.3-Dichloro-4-nitro-5- (N, O, rk, trifluoro-p-tolyl) pyrrole 99 112 91523

Example 69

Following the method of Examples 59 and 60, evaluations of the effects of the compounds of the invention against a variety of insect species are performed, including: 5 cassava, tobacco budworm, southern armyworm, and giant sandpiper. The classification system is the same system used in the above examples. The values obtained are shown in Table IV below. When two or more experiments have been performed with the same test compound, the results are over the age of one; Table A also shows that no test has been performed.

113 91 523 m M o aj o (fl o P Ή 0 · -P tn E oo o o o r ~ - • <D cu CO «04

C

Q)

C I O

• h tn o o

E d QJH

(UMO

(D ω Q (E O O en o o o • p ta o a tn «a a Sp tn co IS 6 o i <04 o U ω a h οσ> en r- 1 tn: tö: t0>

•B

ad CU 00 I I I 1 O 'r- tn o ε o O rH m en en eri en en 0>> 1 o e ε o P OiO en en en σι en en

<O4H

m 2 E o CQ OiO o o (N o o en

E- <O41 — I

O

'o m en en o en en o

1 rH

tn p ns <D Ai Cu tn O E o o o o o o en

rd O O4O I

► * J s Q41 — I m I

I - *

• HI I -H I I II

IX) -H 10 IrHO 10 I · - O

· Η I 1 — I I - * X3 (M> ιΧΙ XI CM I · Η -O

II— (-H 'T> 1 CU Ή p I> 1 P 1 -HP 1 -HI — I p • HO Ή l> (- iH (t3 -HG td Oj «—I (T3 -HP> 4 (0 > p P -H -HCI> .Ai P <D Ai -> iAi P 0 I> 1 Ai H OP -H ECU «N> il 0 * PII> ι IOO rH -P | O> 1 P 04-tie en 0-H m cm G rn o ή i qj n 0 1 — IO »-P Pl -H 0 IH f — IPI -H IQJI-H 1 — I Ai —- EI Ή

Ai <D Ai Ή -H X | ID -H p ih -H iH Ai 0 -H rH -H lp -H rH Ai Ή · Η · Η -H 1—1

^ -P Ή H C · Η I H O * H rH * H * H 0> —I Ή E Ά * —I ‘P -H d H [Il 1 — I -H

0 tn Τ3> ι0 Ό00 OPO-P Ό Ή O -P OPO-H Ό I> iAi 0 -H

Ή -H l>, X IPP t — I 0 P P lAiPP Ρ0ΡΡ Ι'ΤΪηΟΡΡ

O Ό m C P ro-pp AiOP-P iniP-P ΧΙ0Ρ-Ρ m ^ C-PP-P

(0 X - 0) (0 - -H>, I rH Cp-H * 01> 1Ή I Ή> ι · Η -m 0 O> 1-H

EH> 4 PJ 4-1 Ai pj G Oi rr Ai O. G -er ^ OiC m a; a G -i-P - ac 114 91523 ra λ: o λ: o ra o P Ή 0 · • PcnE σ ', o o ct o • 0) a ra «a e

CD

C I o • h ra μ o E ra CD -H JIM Q, <D ra CL E o o o o ct p ra o a, to si i a ΪΡ ra w S E o i <a o U ra O, h I n o ct σι: ra:

•B

: ra CL σι i en σι en Γ ιο o E o

P CT O CT CT CT

0

S

> 1 O

E E o

P CLo ct ct ct ct cT

CL »H

m S E o

CQ CLO (Ti O O CT CT

E-c CL i — I

e »o 05 o ct -cr en ct ct o

1 i — I

ra p ra <D X CL

- ra CL E o o o o o o ra ra O CLo i O X s CL —i i »_ X - 'I i ro -p -P -P -P I -P I' -, —I | ra i i — i »h -P -P i — il -P -P i ι i> * · ρ · ρ

• ΓΤ CN> 1 O ι — I PO-P I I rP rP CN I> i (N> iH H

I> 1 P -P 0 P (H CN -P O · ρ I · Ρ> 1 I · Ρ I £ 5 ο · Ρ

• P C P * P O P Γρ I P P · Ρ · Ρ P, —I Γ0 rp -P φ p -P

> P tl> iP (P> ι> ι · Ρ -P o P P p-UOI-P peppp M O Lp CL -P ^ CL + J + J E O> iL 014-1 -P-P O -P> ί 4->

O -P -P -p -P -P (D 4P OH CL-P o v I ή p OP CL-P

0.-Pprpc OCEra p λ; - e h ^ eiol p o -pc cd λ: ο> ιΟ i ra - ra λ · ρ · ρ o ϋ o pp ^ op o

4-t -p o -Q lti ra · ρ o -p ra ι — i-O -p * p p e * p <—t Dp-O

3 ra rap -μ p -> i.p ra oi> i p ό ^ ρϊρΟ ra 44>. p 1 * -pi ^ ora p- ra>, - p ι · <τ>, ra ι - o CL Λ i-P4-> ra ο Όra l E4C - I> i G m - G 44 iny 3 - p in Ό (D 44 i ° X - CU ι ι ι ro ι cd 'to (D ι -' ι ι * p ra -lii E-ι 3p iro CMIcn-Q ^ lp ro -ct —- lp .p Ai tpn ns 91523 (Τ3

M O

M O

ta o ii γη m 0 · -Peni- o σι o co o • cu a en K Cu e cu CI o • h en Ci o E <a <u »h cu ^ di cUendE en eri σι o en p ta od 10 WK d> 1 en en SE oi <C d. o U en d <—i ^ o't o \ o ^>: nj: ta>

B

: cC

d σι CTi O <Ti <Xi e 'en o E o

Ci r-e m cy * o ^ o

0 S

> i O

E E o

Ci do en en r-- σ ~ ι e ^

d P

m 2 E o C3 do m en o oo o

H d i — I

. O

‘O en o I σι σ> o

1 P

en ci <a cu. * d _ en d E o o o o o o ra ta o do o x d i — i i i M I - ro -

P I OI I -H I

ta I -H -H I I I 4-1 I O I Ή I P O

n (N I »—li — 1 CN I -P I CN P X! I- Ojr-I: fN> ι Xl

I P 0 -P I -rl a P1 -H I P -H Cl -Η I O -H I> i P

-h ci Ci -h -h ci £ i <—i * h en p ta i * p p p * p x ta> p o p p ροι · ρ · ρ p · ρ> i .ui -p p p -p p cu x:

• M O 3> i -P OOPP-P O p> 1 I Elo> rP O P I

^ op d-P O '—il OP O> 1 C m O <N 3 d P 0-PO

O p P e p> i -. p p P> 1 (U I -P ρ ι p p P P I · Ρ pc cu p; -p -p o pi -p -p p -p m -p p -p p xi -p p · ρ · ρ p; O -p p

-e -P T3 P X! -p Ό P> 1 C -P (U .—. P -P -P P -P P C -P X P -P

3 ^ Ό I> 1 p Ό | > 1 d O Ό £ -p O -P Ό> 1 P> 1 O ΌΡ 0 · Ρ

^ I 'S *> 1 ta I Ί1> ί · Ρ JQ I—' P P p I> vU> ιΧΙ I P P P

p p m-cpi in-CPP m i> 1 p p m P ι p p m i p -o p p ^ m o i -o o> i ta -οΐ> ι> ι · ρ -cu ota - dj> 1 -p

p> · -'P tn • «r p>, xi • ^ r- ^ Gdc: - ^ E -PM ^ - d C

116 91 523 fö Λί ο Μ ο 05 Ο 5-1 «-Η Ο · ^ ^ § ο ο <τ> σ> ο • CD Um C / 0 (X di

C

(1) c I p

H M M O

% JS ^ ^ 2 £ o d ^ ° w ^ ^

M K IS CL

> 1 tn ”ϋ I. S ^ ^“ i U C / 0 d ι-H ^ 0 ^ (j,: r0: r0>

-P

dl „c \ σι • q · ct \ σι r- ~ tn o E o

P ι — I

0 σ> σ 'σ \ σι eri

S

> i O

E E o <S3 σ 'σι σι σ' σι ro S Ε ο Q d ο _ Ε-ι d * —ι σι σ 'νο γ- ~ σ' ο 1 ο 0 σ 'σ' σ 'σ' σι

1 ι — I

tn ρ (0 φ ^ d Λ tn d Ε ο _ fö ro ο do ο ο ο ο σ 'O ^ ~, - (

JX I

-P I I I 7, m n i CM i -. i - ι ι V i

1—1 · ιΗ · Η '—'10 -HO I -H O in * - I -H

- | I. — Ii — i I 00 I Ή X! N H J0 - - CM * —I

(N τ | O ‘H fN Ή 0 CM>, p I> 10 y I 0 -P

s, *> I 0 0 * H I ι — I rO I> i t0 · Ρ> i fO I ^ * P P 1 — I

• L ·, -H O Cl Cl -p>, a; -C C ϋ CCA! -H ~ C Ci -H

£ 2> i-P £>, I £ CU I O Φ I ι — I I O> ι · Ρ P O ι — ι d-H OCn o * p m o 00 m> iCM 3 d 0

v fl. P 00 - C Cl (D I · Η Cl O I -ή ι — I O I "H> ι I

i) 00 Ή * P O 00 00 Ή ι — I 00 Cl * P ι — I 00 Cl * P ι — I tn Ή 0-1 * P * H

Ί3 rn Ή 'O ι — I 00 Ή Ή H Ή · Η -Ρ> —I Ή · Η -Ρ ι — I · Η -Ρ £ Ή ι I C

f — I, I τί I> 1 0 Ό 0 0 · Η Ό · Η Ο · Η Τ3-ΗΟ-Η C Ο Ρ> ι Ο ρ rrj l ^>, ra I Ο Ρ Ρ ICPP I GPP Φ Ρ -Ρ > 100 t ~ r ~ m ^ e 00 m ei ρ -P mip-p miP-P 0 0 ι p 0 tl>, -m φ ι μη>, - p * CM> ih -CM> ip 1 -π- y 0 to a · 0-in ^ 00 d C - d C ^ - dC 1 — I Ό ρ -Ρ Λ! ii7 91 523 Π3 λ; ο Ο ο d ο

d ι — I

Ο · -PtflE m ο ο ο ο • QJ Ο, co κ Οι

C

ο C I ο • H tn d Ο Ε d Q) Μ

QJ O D

(D Ιβ D Ε ο ο ο ο ο 4J d O D tn «s α tn ws ε ο ι <α ο O CQ Ο-ι · —ι 0 ο ο σ σ: d>

•B

II II

r ~ tn o E o 1-1 σ o σ o o 3

> i O

E E o σ σ σ σ σ ίΧι ι-ί ΓΟ 2 ε ο g α ° 00 '^ ° ο. ° σ cn σ co r ~ - ι tn d d α) Λί Cu d!? π n S ° o o o r->

X d O Dj O

M X = αΓΗ I I

-P - I d I I

d -dl O> 1 DJ I I - · I

-σ I rd O 4-1 Qj I O I I -d • 'r -d O

- rsj>, 0 | drs 1—0 CSJII -d t — i I - Ή O

I> t d (N 3 -d 'I fM -d d I * d (dj | H -d uO Γ0> i d - -dCd I CO »—10 l-Hd -d d" J - O -d v—- (ti

; f * d 0) O -d-d>, 0 -d>, 0 dOiOdd ^ RiCO

M 04-l | g .h>, d E> i I O O> —ι -d d -P I <N 0) I

-, O 0 ro 0> iCd O CM o OI -P>, - d -dl 4d ro H ι — ICI -dd> i G) O -dd OI -d rd O - -d Dj C rd -d -d I -d ~ ~ X m-dH O -P * PI rd O 4d -d> —IX -d -d H ^ o>, dd-dd O t: -d (0 d -d -d 0) - ro -d -d -d Ή -d -do Ή> i-d'XI> i OOH -d Σ, li O> i O -d Ό E -d I -d Ό d 0 -d ΐ I> i> id d -P000-d 11 11 Itndd I -— <—ι -dd lOdd | -a->, -p> i <3 <u, -c, -n d d z. μ m ι d -p m ι>, .- 1 -p uo o d -p m - c <D> ιϋ E M O d -p £ ~ - DJ> i -d * ·. DJ> ί 0 -d »d 3rd -ro 0) E 4-> I I -d -d>, - d

^ - DC ^ d- :. G d C - ^ ODC τί- - id - d) ro, d O Ό D C

118 91 523

fO

^ o

Ai O

03 O

i-J · Ή O · ^ ^ en en oi W K d c

(U

CI o • h tn μ o E Λ 1) H d) Λί Dj 0 tn de ^ „„ -PttJOQj ^ ° en tn «kd> 1 tn cm SE o 1 <Q <ou tn Di h _ en o o- < n: rfl

: CIS

> Ή: o3 m a, _ O en I eri m γ- ~ tn o E o μ -h 0 cr. eri eri en in

S

> i O

E E o μ ao <; Oj <—I eri eri en en eri ro 2 E o 03 do

En Qjr — i tri er. o tn o o o • o en i LO tn en

1 iH

tn μ 3 0) Λί di ed ^ tn D, Eo S tti O diO m i in ld o o .S ^, -

-d · Η I I-H III I

^ I I — I -H>, | 4-ί 4-> · Η | | -. |

e-1 I -H O Ή μ> i O I O -H μ I -H LO 'T -H O

- ι-Η-μμΓ-ι OCX! lo I 4-i C OCrH »*, μ X

ινομ · Η oo μ i-hoji o ω ι · μ ^ ro>, μ> · Η 1 O> 1 · Η H μ (3 · μμ · - '·> ί · ιΗ μ · Η · Η 1 -—> -, ra • μ μ '"-' αμ Λί -μ Λί μ ο ι ι ι Λίμμ μ · η ι e λ; 014 -) -. 40 I μ I Ο 0 Ή - I μ o XI — 104 0) 1 Ο Ο ΟΙ · μ -μ · η ί Οο 0 Ή I · μ -μ lo Ο μ -μ>, ι μ ο Λί 0) Ή ι μ ιΗ C ΙΟΙ · μ μ Λ! - μ μ IOμC> ι-μ - μ I · μ Xί X ίί · μ μ> ι Ο · μ μ · μ μ Λί · μ · μ> ι Ο · μ η> ι O tn μ μ μ μ 3 tn · μ Ή I> ιΧ ΕΛίΉ-μ · μ Ό Ή> ι μ Ε Λί d X μ Ο Ο Η · μ, μ -μ ό μ ο ι ο -μ χι> ιχμ ο ι - μ cooo-μ 3 χ ι> ι ο ο π3 μ ο ^ μ μ ι μ-> ι ω> ι μ oj-μ (¾ qj> —ι —ι μ μ 3 X LOX -4JX χ — μχ η. C £ d Χ-μ 4ί ΧΛίΧμχ Ε-ι> η - 0) X ι ι II> ι · μ - ro Ο -μ Ο Ι Ι> ι Ι | -μ · μ>, · μ ^ £ dro Looidc (Μ '' μ tn μ μ · οί >> ro xxxdc 119 91523 rt X o λ : o ra o

k-l f ”H

o ·

| J O g O σ σ σ O

• cd a en k a e 0 e I o

• H CO U O E <0 <D r — I

qj λ; a Φ n a E o σι o σ o -M ra O Oi m «s a> 1 en co S E o i <a o O co Οι ή en σ m σ o: rt: rt>

•B

: rt Οι γ ~ σ σ σ σ r- co o ε o 0 I — I σ σ σ σ σ Ο

S

> ι Ο ε ε ο Μ ΟιΟ σ σ σ σ σ Οι' — ι ro en S ε ο C3 Οο 'S' σ οο σ m (Η Ο ι — ι; ° • ο σ σ σ σ σ ο 1 - 4 C0 ο ra ο λ; ο en Ο Ε ο ο σ ο οο ο rt rt Ο Οο ι Ο ϊ * ί Ο O'-Η I - λ; ι - ι m ή ι ι 4-4 - III -rt I - -> —I .—. I Οι rt -H -HI Λ'ΗΗ o I -HI ι> ι Ή Ο - I Ο

• ι ι I I Η ι — I ι — I -Η 44 „Q 'S r-H -rt CN Ν'— I -Q I - ~ -Q

- -Η>, 0 I Ή 44>, 44 '> ιΌ · 4 IC>, 44 Γ0 -O 44 * · 44 Ή £> -, I i — I rt 00 I' —I -rt (D rt I · —L ra> I ro C 44 -H 4> IY04I - C * 3 · -H 4 W c ϋ Ή>, Ä

Μ ΓΟ - Ο> ι-0 0 4-1 0 4J | I O “4 0 * 4> i I E> I

- I ** 4 o -P 0 1) - I ro in W N 4 o O O ro 0C (N

0 (N LO -OO rt 1-4 E 'vo I -r4 I * γ4 I 4-1. — I 0 OI Ή 4-1 OI Ή 01 0) II 44 C rt ϋ · 4 0 ι · Η 4 · 4 4 · 4 · 4 X Ο 44 · 4 ι-4 Ο Ή · 4 Η X 4-1 -Η -Η 0 rt -Ο -γ4 C /) - -Η ι-4 -ι4 Ε 0 | “4 C -Η ι-4 Ο »-4 -Η Ή -Η * -4 -Η 3 rt Ή 4ι O rt Ο 3 Λί Υ 4 Ο · 4 0 Ο Ο 0 Τ3 Λί I Ο · Η Ό 4 Ο · Η Ή - Η> ι0Η>, 01 I 0 ^ 0 44 44 4, Η 4) XI I · Η (ΝΙ 44 4 104444 ο> -, o Oi en rt ΙΟ -O - 3 44 -Ο £ 1 -ϋ 44 44 1003- -44-0 10 O 4 44

rt X 4J1 — Ι-ΗΪΙ -OI' — I> 1 -H | -r4> irt -ΙΙ ^ ιΌ * · —I> 0 * H

h> 4 h x ό s h "^^ - γμοοο ora 'S'-s'i-hoc -ί m oc 120 91523 rö

X O

O

tfl O

P I — 1 0 · 4-> tn g i— σΊ σ o o o

• cu CX

m «a.

e

(U

C I o

Ή ti] M O

E <T5 (1) M

a) Λί Qj Φ in ae o o o o σ o W n) o a m x e a> 1 en i <Λ S E o ι <Oj o 0 U3 Qj r-1 LO O O O σι o: iö>

•B

: a3

Qj σ σ o σ σ σ Γ 'm o 6 o

Dm σ σ σο σ σ Ο 5> ι ο e ε ο Ρ QjO σ σ σ σ σ σ

Dj '—I

η s ε ο W DjO σ σ ι ο σ ο £ -1 Dj Μ. Ο ° σ σ ι (Ν σ σ ο 1 Μ CO Ρ (¾ Q)

-. λ; Dj I

n) in Qj Ε ο γ ~ ο ο ο ._. o γ ~ ο Π3 O QjO.

«S DjM I,

t! 1 —I I -M I

<3 II Ml MM I M M> 1 I I O I

'M MM P M M MMM> i in-P O M P 0 - dm O I M M I> 1 o m> 1 I>, (D X! Ρ -Ρ X) OO O M o M m>, p M C'TM CEP 0 M p

- OPI Μ Ρ D M I C Ρ M 0) | M ¢) M fl OCfO

h * Μ Ρ Ο .Μ Ο Ρ P M <D>, p 4-4 CO Μ 4-1 Ρ Λί M I M

Μ Αί> ιΧί I Ο in -P EMQj-P II M I O I X if> \ M Dj P M M DjM o m m m in M P tM 3 η M I ΓΟ

2 „Ό - (0 M I - C Ρ P M C IM-P I ι — I I Μ Ό -> I M

M D I M X M M M M O D O> t 0 MOM M 4-1 M M I M M M

M -P 'ST Η Μ Μ Ε Ό M X) MO> iXI EDC g M M M M M M

• j 2 ^> ιΌ Μ 0Ι> ιΡ Ό Μ -Ρ P O D O ODOM “> iOM

Μ ~ Μ> ι I D Ρ M>, Ο I Ai CU C p in XI p-ppproinpp 2 32 '-cm-d xi - e x: m ι g λ; xi Qj p xi — p-p ~ c ρ -ρ

z £ I O * · M I Π OJ I * Qj I I I M rtj ll> (M I (!)> iM

m ph mPN e m ^ 4-4 m - min n m ^ ^ mOiC m p a C

121 91523 rt a: o

Ai O

rt o 5-1 P

0 · _p tn g oo θ '»tr ro o • <D a co« a c Q) C I o • rt U) 5-1 O £ rt d) ή ai λ; a Φ tn O. goot— ld ct -pmod tn «a: d> 1 tn co 2 £ oi <do UCOdi-H oo tn CT CT o: rt: rt> rt: rt dm tr ct ct or ~ r- tn o E o

5-1 I — I OCT CT CT CO CT

0 s

> i O

G E o

5-1 do <T CT CT <T CT <T

d P

ro 2 E o aa do o ct ct ct o r-

E-c d P

122 9 1 5 2 3 ο Μ ο Π3 Ο i-l * “Η 2 ή ε ° 00 οο. ο) α, tn «α c ο C I ο • h uj μ ο Ε 10 ΟΗ ϊ μ αε ° m ° m ^

-n <ο ο α tn χ, ε α> 1 UI I

cn S ε o UM α S ^ O '° O' O ': rö: α3>

••B

~ Qj O 'οί en en n ~ uo o § 2 o' en en en en

O

3

> 1 O

U α§ ^ ^ ^ en en

* £ Cl »H

ro 0 cL§ o> en en o en E- * di i — i o o 1 2 o ^ en en en en UI J- |

ro di Λ Λί CU

ra tn α ε o tn ° ~ O 'en n en eo “n 1 11

^ I I I IM M

• m I -— · Η · Ή 'O I I in>, I I f0 III r — Ι · ΗΜγ-IX! O O - I Λ eN>, λ; (N · Η> 1 I -HII — IO> i> -l MX · <Τ IX ι \ I |>, | ^ I ^ ^ 'ΊΗ Ή> i 3> i 10 IM S- {I »CX <D -Hl O -H Cm f, -MOCI -HM>, iH Cil -H> i ro -MM gh Λ M 0) |

E 3 O) -H -H O X X QJ I M (Χ, λ; X CN -H> i M O X -H -H

o O X X X M O 0) X X m OI -H> 1 I M> i ro O X X X

_ £ m M tM -. O X X E tn I X O - TS -M> iX O C Λί X Ή M O -M

v jj XI -H -HM -HX -HX -H -MX XXIX UI M 3 QJ IHXOM Ή _ XM UI MCX U3 - UI XX ΛίιΗ- ^ Ρ-Η XOXX m XXO Cl Cl, x τι x λ:>, o ό mimo · η i - xeowi -h tj x>, x

n rr- <I O CX X I O iQ-t O Cl M £ X M GJ <—I X X X M I Λί QjX

ra _c m ι x ^ m m x x m x -'Cix Xlil Ij ran + j m i - * e c_, r; ~, cu <ux 'ra - ai ι ω Shx i Qi-hh i -hxxo -h - am o ^ ^ ΕΗϋ <ί - IN E dc in HHC HO- O ti C -ί-Ηΰ 123 91523 m jm o JM o

Π3 O

Li i — i

0 O O CT O CT

-utn e • a) a, LO OS d c 0) C I o • H M U O 5 ΐϋ d) m OJ JM d σ \ cr, «τι t- ~ ro ai m Cu E nm o a M« ffi d in

M

ws E o

I <C d O (3 o 03 O O

O C0 di Ή «0: ic>

♦ H

cr r ~~ cr cr cr M-i CO o

S ° CT O CT (T CT

Li i — I

O

S

> i O

σ ', g-, g-, g-, CT

Li dO

^ Cl i — i ro a cLo T4 o (T o in

H CU '—I

124 91523 ra X o

Ai o (O o

t-l r — I

0 · m o en oo -M tn £ • oi a, tn «a c

CJ

C I o

-H 0) t-l O E fÖ QJ H

CU Ai Dj O <n O O

ti »tt £ u« o a tn x s: a.

> 1 tn tn s E o l <C Qj o o en σΊ oo

U W D <H

: ra: ral>

•B

^ en en <n r- tn o S ^ <n en en en

O

3

> i O

S E o en en <n en

t-ι QjO

<1 Q-j Ή ro S E ° o o o o O di o co Q-ί I-f / ° o, 2 en m r- tn> -i ra o

At a en Cu E o n ^ 5 n ° o LO rr r-

^ I

«1 I

® Il I LO I -H -h 'I

-ΓΛ (N I I o II II e-vj | .—. | S_ |, —1 -H

I -H o JC I o U I I -H -H S-l O> iT3 -H

. - -H C C Cl —I * H -H 0 i> i 0 -H tl H β 3> ilr-l o u o e ra> 1 ή u i — i ac e o>, Ai .h q ^ -h

M 00> iAi> 1> 1 O Ai -—- Cl O O> 1 I -H U-IOJ ^ .H

0 · —i Qi-h tn>, o -h -h ra o h e η h · η ή in u

^ ^ Ό -H -P +1 H ra H Ai -H H ϋ 0) | -H tu -χ I -P

- * ω Ai -H · Ή | e | COMI>, 1 H x -H 4-1 -H -H U-l · Η -H -H

ΤΊ · ιΗ Ό> —I ro -H 0 E Ή Ν '> | Π · Η · Η ra · Η H tl - 03 ι — I C

• j tnra i> i »-H jc - ra - e i -hra i t o u iacoo„ 22 I ^> i.-H i-ι χ-; -P | ro o -h t-ι IO tl -H, αο ΚΛ -J Ό LO - CI 4J \ lt / 3 LD - Ml I — I -tJ LD χ q tl C 4-1 tl Slra XZ x ro Ο Ή · Η I Ai x I -H o -H xfNH>, OIO> i (0 tn 'ΐΤ -—- Ml. — Ie H ON · M t tl C -O' —- 't-Ι Q, £) enECLAi 125 91523 ra M o pe o ra o

S-J <—I

0 · o o σ o

4-1 tn E

• O Dj en oS Dj

C

GJ

e i o

H li] O

E ra D Ή

<U Λί Qj σ o O O O

Q) ID Dj E

-p ra o a tn tlS OS Dj> 1 tn en s E o irfIDjO σ o-, o σ σ U en ft h: ra> Ή: ί ^ σ σ en σ σ

Dj tn o

Bo σ> σ en en σ D r- (

O

S

> i O

B B o σ σσσ σ ft Duo Dj r-1 ro SEo o oenσ o

a DjO

En DjiH

; o o 2 e »σσσ σ tn ft ra o -¾ Dj (3 tn Dj E o O ® S? £ 31 ° ° en en o σ

V μΐ mm * -L | rH

-P I

ra i O i

σ II I -ft -ft ft O I I

- i — i I CN I I (Nil I · —I 14 4J D I tft Il -rl I C I -H 0 I -H Γ0 I -H -H o -H ft UI> ι I · Η I -P Τ3 -ft

. -H 0) -H ft ft -H ft '—- -rl H -rl O C ra I C m r-4 Dj G) -rl' I rH

r> ft 4H rH O ft I ft O I Dj O ft h I ^ -ft O I -ft VJ E rH rr -ft M O -H> i O>! O OOr-IOD + J Λί'Τ I E'P-rl-rl I -ft>, v -ft _ Ο ft> ι-Η DjXi O i — II ft ft -ft -HI (N 0 -rl -HD m H>, N tj

S m H H Dj> J C Or. | -H ft ft O -P I O C I -P

• fj ^ y 0 1) -rl P ra p a; -rl -rl | Dj O | -H -H rH Λ O ft - <H H 3 0) -H -H

-ra -HHE ra H Ai -H -H ral H (N rv Xl «JHH-H -ft O ft CEPH ep RaftS-v |>, 1H T3 l>, I -ft ft -3h0-h TJ rH>, OO p - ooj 2- ll-H- ^ SprOP I> 1-HH m ro>, ft ft IPSDjJD pP-HPAft E:% m Dj tn> q ι -P m ~ q raJ VPe q ft -P ip Xjptnpp P ~ --- Ά O dl-HH v ΓΟ ra o> 1 II (D> 1 -ft vDj-Hra I -P PS> 1 <T3

era · * ft · V> O ^ P4 Ή q - W -n e tn in P ft C (N '- HA! ro - Q Dj PS

91523 C3

M O

X O

tO o P <—I

o σ en • φ a. tn «a.

e 0 e I o • H W P O E m li h OJ · * ^ o o o o o <d w a ε -p to o a en «n: a> 1 tn to s ε o.

Sηα S ° ° ° ° o: <ö>

•B

σ σ \ σ σ σο r'- tn o σ en σ <τ \ σ '.

Ο 3> 1 Ο g Eg σ σ σ

Qj Ή co m a§ ° o σ σ σ E- · CX Ή o o 1 2 σ en σ σ \ tn p to o λ; a A tn a ε o 0 5 5 n S 03 en o o r- '

^ a _ a a I

P I

- I I I I i i "P I

• σ I -H | -H I>, -H -H -H -H I O -P ~ I Γ0 'f h · η -π> i ι i a a ρ ρ ^ χ tu-oOi ->, H -H I -H P | -rl ID -HO -HO -P -HP ε »* -P -H · Η ^ n> io -H aaiajroi — II ppa O 'Ή nj a - iaaf, —- e P p“> im EI -h - ho PP and ι>, λ; pv O a M IQJP4-) I> 1 I Ή Ή · Η εθ> ι-Ρ A "m>, I Ο ^ ΙΡ-Ρ tn Ρ>, · Η (NC · Η Ρ Η ρ O-na-H - ΗΙ4-ΙΓ0 Ρ '-'- ΗΡΡ HI -see I o rH ο ο -p ρ λ; ^ e ό - oj ι haip>, -p

~ r <-H P o O -H tp 3 P -H X! -H -H o I -H ε -H a a (M o a-H

~ γ E O ΡΛ ε a>, a p e -ηόηχι a a a a a i 3 - * C

"i oo-pp op -pa>, o ό i> p ~> ipoapaao rrt P aa ro POtu-nax ia> i to m> iOPP aaaa χ £ ^ ΧΛίΠΛί £! 0 ε P ~ P ^» CM C 3 P a - aa> ipp ^ ir; i-Hii iaiaa to -nm ι i uh>, - hi>, p>, ro “^ n O ^ naa —ή ϋ m - p γμ cm aa pj C tn> ι- Ρ h λ: 127 91 523 rö

M O

M O

ro o Γ “| 0 · en o o o eri P en £

• QJ CL, en K CL

C

0) C I o Ή t / 3 Ci o E tO QJ ip QJ λ; cl o o o i o

qj tn CL E

L m o CL

tn LC CC Cu

Sn tn en s e o I eC CL O o o o i o

U en CL rH

: rö: tfl>

•B

cr cr o cr cr

CL

Γη o E °, cr cr o cr tr

Ci ip 0! * _ Un

> 1 O

S G o cr cr r— cr cr

Ci CLO

Cl '—i en § o o m o eo cr

03 CLO

E-ι CL i — I

o ‘o, 5 cr <r cr cr cr

1 H

tn o (0 Q)

Ai CL

^ tn CL £ O

O 5 o o o o cr

v1 HM MH 00 fP | I

-P - „n) · ρ i -hi

• m Ή O Ή O I li II

~ I> 1.0 I> iXl I I en -Ρ I —h I -. I

Ί ·> 1 O ^> 1 Ο ιη-ΡΙ-Ρ Ρ -Ρ P l-P> i -PP

m ien ien ioj-p-p i -P h d clp>, p n p; -P QJ Ai -P QJ Ai -p £, p-p CL '"> nA £ Ϊρ-Ρ I> iAi

M £ L-ι | £ L-ι | rP -P O -P I I> ι I -P I> i CU -P Sr I -P

Ο-Pen O-PtN Sr Ρ Ρ P in in P m P (N C £ PLmri

H .. p p | -P p p I -P>, o P -P I I <U I -P I QJ -P -P 0) I -P

n jn CJ O H p J3 o -h h i — in 3r * P · ρ · ρ £ * p · ρ -p p tn - '£ -p · ρ n γ. · Ρ o ή · ρ · ρ ο ή · ρ ο ρ α e ε Η · ρ η ρ ε · ρ λ <ι · ρ γρ ρ · "“ 1 ΌΡ Ο-Ρ η ρ Ο · ρ -Ρ uo -— η Ο o Sr Ρ Ο -Ρ Ο Ρ O tn Ρ 0 -Ρ 'Ρ', Ρ I Ai Ρ Ρ I Αί Ρ Ρ I · Ρ · Ρ Λ Ρ> ι Ο Ρ · Ρ Ρ Ο -Ρ I Ο Ρ · Ρ

η η ίπιρρι inip-p CLPrPp Λ Ρ 3 Ρ C Λ Ο ΦΌ Ρ C

~ 'CL> 1 · Ρ - CL> Ι · Ρ I -Ρ Sr C3 I OH> ιΟ I Η' - '-Ρ Η> ιΟ ^ ^ cncoCLC m'— CLC cn ^ SrAi ^ -Ρ 4-1 CL X ! Ρ · Ai, ρ rP ip CLX1 128 9 1 5 2 3 ra λ: o λ: o ra o P <—i

Sm e ^ ° ^ °

• 0) CL LO X CL

C

<D

C I o • h m ci o E ra <D <—i S m α e ° ° ° 1 -ci ra o cl m x k CL> 1 m i

w S E O

ύ m ä h ° ° ° 1: ra: ra> • r- \: n3

CT »O CT» O

m o £ o

^ _l j d? CT

0 s

> i O

E E o

Ci CLo it. eri cr <σ \ * £ I CL Ή m S E o aa clo o o o o £ - * CL Ή

O

* o o 1, _ (σι n in o ~ m ci ra o

Li CL

- ~ · m CL E o S ra o clo

O V- CLr-H (TO TO

Li ^ III

O I .—. -H .— ra -—. I> · Ι I -P I rP | -p

n I -P -P I vj -H | | -H i — I O> 1 · Η Ι-H I

~ '»H <11 ra V p I -H ^ p ap-Q>, P> | -H

: · - iP EI Ή '-' OP -P PPL> i P 4-1 4-1> iT3 -p • p> roac-H-Hi — ii ra ao i> —i -p> —ι i <- ira οι »—ιι» —i

l_l '- C P Ή -h ra P CL-H -H —1> ι · ν> O Ai E V O ^ -P

icuoo-p i p - ra) -P i ao v 4-> ι i C -u - -p

0 04 Page 3 P P -P-P-PIP LO 4-1 - I ra H - I N P

m l-P'— I P 4-1 P P H »T 4J lOoO ^ l-P I 'χι CL I 4-1 k * I i -P p LP ap * P Cp 4-1 r-H -P £ - | Ή i— | -p v | · Ρ · Ρ 01 [f] E o · ρ a c ap i apo4 ra £ -p - .p, —i * p £ - · ρ i — i ra

-H OOPr ^ o 4-igrP | o OPvPO-P o v P O O

3 T> P P L -P XI O) f 0-PX3 PO-ΟΡΡ P-OPX2

(3 x; X) Li '- P P £ r4JrPP X3 3 - 3 P 4J X - 3 P P

> h i -p i> 1 ra i n, i o ra i <—ι i <—i ap * p ι i —iapra

T3 m LL h '-¾1 lp 04 lp CL C ra in P LL

129 91 523 n

Ai O

Ai O

ra o

P i — I

0 · OO I

-pm e • O) &

CO Di CL

C

0) C I o -a en p o

E Π5 <U »H

(D Ai CL I I

ei m αε

• P (0 O CL m ui 2 CL

r O

m en S E o i <CL o i i U en CL -h

M

M

>

•B

I I

CL

r ~ en o E o σι i

P rH

0 s

> 1 O

E E o οί o> P CLo rrC 0-t i — i

C/O

S E o σ I

eQ CLO

t- <CL i — I

Claims (8)

91623 Patent Applications 1. A compound of structural formula I is Y N ' A wherein X is F, Cl, Br, I or CF 3; Y is F, Cl, Br, I, CF 3 or CN; W is CN or NO 2; and A is H; C 1-4 alkyl optionally substituted with one to three halogen towers, one hydroxy, one C 1-4 alkoxy or one C 1-4 alkylthio, one phenyl optionally substituted with C 1-3 alkyl or C 1-3 alkoxy or one - three halogen atoms, one phenoxy optionally substituted with one to three halogen atoms, or one benzyloxy optionally substituted with one halogen substituent; C 1-4 karbalkoksimetyyli; C3-4 alkenyl optionally substituted with one to three halogen atoms; cyano; C3-4 alkynyl optionally substituted with one halogen atom; di- (C 1-4 alkyl) amino-carbonyl; or C 4-6 cycloalkylaminocarbonyl; L is H, F, Cl or Br; and M and R are each independently H, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 alkylsulfonyl, cyano, F, Cl, Br, nitro, CF 3, OCF 3 or R 2 CO, and when M and R are in adjacent positions, they may, together with the carbon atoms 30 to which they are attached, form a ring,. wherein MR represents the structure: • · O · 91523 and R 2 is C 1-3 alkyl or C 1-3 alkoxy. Compound according to Claim 1, characterized in that it is 4-bromo-2- (p-chlorophenyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile or 4-bromo-2- (p-chlorophenyl) -1 - (ethoxymethyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile. 3. A method of controlling insects, nematodes and mites, characterized in that said insects, nematodes and mites, their breeding sites, food stores or habitats are contacted with an insecticidally, nematicidically or acaricidally effective amount of a compound having the structural formula: Wherein X is H, F, Cl, Br, I or CF 3; Y is F, Cl, Br, I, CF 3 or CN; W is CN or NO 2 and A is H; C 1-6 alkyl optionally substituted with one to three halogen atoms, one hydroxy, one C 1-4 alkoxy or one C 1-4 al-. 25 thylthio, one phenyl optionally substituted with C 1-4 alkyl or C 1-3 alkoxy or one to three halogen atoms, one phenoxy optionally substituted with one to three halogen atoms, or one benzyloxy having optionally one halogen substituent as a substituent; C 1-4 karbalkoksimetyyli; C3-4 alkenyl optionally substituted with one to three halogen atoms; cyano; C3-4 alkynyl optionally substituted with one halogen atom; di- (C 1-4 alkyl) aminocarbonyl; or C 4-6 cycloalkylaminocarbonyl; L is H, F, Cl or Br; and M and R are each independently H, C 1-3 alkyl, C 1-3 alkoxy, C 1-6 alkylsulfonyl, cyano, F, Cl, Br, nitro, CF 3, OCF 3 or R 2 CO, and when M and R R at adjacent positions may, together with the carbon atoms to which they are attached, form a ring in which MR represents the structure: and R 2 is C 1-3 alkyl or C 1-3 alkoxy. A process according to claim 3, characterized in that said compound is: 4-bromo-2- (p-chlorophenyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile; or 4-bromo-2- (2-chlorophenyl) -1- (ethoxymethyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile. 5. A method for protecting growing plants against insects, nematodes and mites, characterized in that an insectically, nematicidically or acaricidally effective amount of a compound of the formula I is applied to the foliage of said plants or to the soil or water in which they grow. the structural formula is: 25,; ri- »jVMr 30. N A wherein X is H, F, Cl, Br, I or CF 3; Y is F, Cl, Br, I, CF 3 or CN; W is CN or NO 2 and A is H; C 1-4 alkyl optionally substituted with one to three halogen atoms, one hydroxy, one C 1-4 alkoxy or one C 1-4 alkylthio, one phenyl optionally substituted C 1-3 alkyl or C 1-3 alkoxy or one to three halogen atoms, one phenoxy optionally substituted with one to three halogen atoms, or one benz-5-yloxy optionally substituted with one halogen substituent ; C 1-4 karbalkoksimetyyli; C3-4 alkenyl optionally substituted with one to three halogen atoms; cyano, C3-4 alkynyl optionally substituted with one halogen; di (C 1-4 alkyl-10 H) -aminocarbonyl; or C 4-6 cycloalkylaminocarbonyl; L is H, F, Cl or Br; and M and R are each independently H, C 1-8 alkyl, C 1-3 alkoxy, C 1-3 alkylsulfonyl, cyano, F, Cl, Br, nitro, CF 3, OCF 3 or R 2 CO, and when M and R are in adjacent positions, they may together with the carbon atoms to which they are attached form a ring in which MR represents the structure: 20 'and R 2 is C 1-3 alkyl or C 1-4 alkoxy. Process according to claim 5, characterized in that said compound is: 4-bromo-2- (p-chlorophenyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile; or 4-bromo-2- (E-chlorophenyl) -1- (ethoxymethyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile. A method according to claim 5, characterized in that said compound is applied to the plants or to the soil in which they grow in an amount of about 0.125 kg / ha to about 4.0 kg / ha. A method according to claim 5, characterized in that said compound of formula I is applied to the foliage or soil of plants or to the water in which they grow, in the form of a liquid combination containing from about 10 ppm to about 10,000 ppm of said compound of formula I compound. Il 91523