ZA200303012B - Pyrrolcarboxamides and pyrrolcarbothioamides and their agrochemical uses. - Google Patents

Description

od ’ > WO 02/38542 PCT/EP01/12830

EJ

-1-

PYRROLCARBOXYAMIDES AND PYRROLCARBOTHIOAMIDES AND THEIR AGROCHEMICAL USES

: lhe present invention relates to novel pyrrolecarboxylic acid amides and pyrrolecarbothioic ) acid amides which have microbicidal activity, in particular fungicidal activity. The invention also relates to the preparation of these substances, to agrochemical compositions which somprise at least one of the novel compounds as active ingredient, to the preparation of the sompositions mentioned and to the use of the active ingredients or compositions in agriculture and horticulture for controlling or preventing infestation of plants by

Shytopathogenic microorganisms, preferably fungi.

The 3-pyrrolecarboxylic acid amides and 3-pyrrolecarbothioic acid amides of the present invention have the general formula() / :

X

R, _Q

N

N H oo

HR

R, wherein

X is oxygen or sulfur;

R, is CF, CF.H or CFHy; :

Rz is Cy-Caalkyl, Ci-Cshaloalkyl, C-Cjalkoxy-C,-Cgalkyl or C-Cshaloalkoxy-C4-Csalkyl;

Rj is hydrogen, methyl, CF; or fluoro;

Rs Rs Ry R,

Rs Re S Re 7 S Rs . S ]

Qis Qn , oS (@) CS @ SQ ;

R{ R, R, R, - R, is Ce-Cisbicycloalkyl unsubstituted or substituted by methyl, ethyl or CF;

Ce-Cusbicycloalkenyl unsubstituted or substituted by methyl, ethyl or CF3; * Ce-Cusbicycloalkadienyl unsubstituted or substituted by methyl, ethyl or CF3; or a group of the form oA

R, . wherein R;, Rs and Rg are independently of each other C,-Cjalkyl or

R; Rg ’ C:-Cshaloalkyl; or a group

Ryo : Hn, wherein Ryo and Ry; are independently of each other hydrogen or

Ri (CH), halogen and n = 1 or 2; and

Rs and Rg are independently of each other hydrogen or halogen.

Surprisingly, it has now been found that the compounds of formula | exhibit improved biological properties which render them more suitable for the practical use in agriculture and horticulture.

Where asymmetrical carbon atoms are present in the compounds of formula |, these compounds are in optically active form. The invention relates to the pure isomers, such as enantiomers and diastereomers, as well as to all possible mixtures of isomers, e.g. mixtures of diastereomers, racemates or mixture of racemates.

Within the present specification alkyl denotes methyl, ethyl, n-propyl and isopropyl. Non- branched alkyl! is preferred. Alkyl as part of other radicals such as alkoxy, haloalky}, etc. is understood in an analogous way. Halogen will be understood generally as meaning fluoro, chloro, bromo or iodo. Fluoro, chloro or bromo are preferred meanings. Halogen as part of other radicals such as haloalkyl, haloalkoxy, etc. is understood in an analogous way.

Bicycloalkyl is, depending on the ring size, bicyclo[2.1.1]hexane, bicyclo[2.2.1]heptane, bicyclof2.2.2]octane, bicyclo[3.2.1]octane, bicyclo[3.2.2Jnonane, bicyclo[4.2.2]decane, 0 bicyclo[4.3.2]undecane, adamantane and the like.

Bicycloalkenyl is bicyclo[2.1.1]hex-4-ene, bicyclo[2.2.1]hept-2-ene, bicyclo[2.2.2]oct-2-ene ’ and the ike.

Bicycloalkadienyl is bicyclo[2.2.1]hepta-2,5-diene, bicyclo[2.2.2]octa-2,5-diene, and the like.

One specific subgroup of the compounds of formula | is the group wherein X is oxygen.

Another specific subgroup of the compounds of formula | is the group wherein X is sulfur.

Preferred subgroups of compounds of formula | are those wherein : X is oxygen; or

X is sulfur; or

R; is CF3; or

Riis CFzH; or

Ry is CFHy; or

R: is C4-Caalkyl; or

R: is C4-Cshaloalkyl; or

R; is C4-Caalkoxy-Cy-Csalkyl; or

R; is C¢-Cshaloalkoxy-C;-Csalkyl; or

R: is C4-Caalkyl or Ci-Cshaloalkyl; or

R; is Cy-Caalkyl, C4-Cshaloalkyl or C4-Czalkoxy-C4-Csalkyl; or

R: is methyl or CH,OCHj5; or

Rs is methyl; or

Rj is hydrogen; or

Rj is methyl; or

Rais CF3; or

Rj is fluoro; or

Rs is hydrogen or fluoro; or

Qis Qt; or

Qis Q2, Q3 or Q4; or

Qis Q2; or

Qis Q3; or

Qis Q4; or

R, is Ce-Cyobicycloalkyl unsubstituted or substituted by methyl, ethyl or CF3; or

Cs-C1obicycloalkenyl unsubstituted or substituted by methyl, ethyl or CF;; or

Ce-Ciobicycloalkadienyl unsubstituted or substituted by methyl, ethyl or CF;; or a group of the form

Ry

YY wherein R;, Rg and Rg are independently of each other Cy-Caalkyl or 7 8

4 =

C,-Cshaloalkyl; or a group } Rio

NY Vr, wherein Ro and Ry; are independently of each other hydrogen or ' Ri (CH, halogenandn=1 or2; or

Rs is Ce-Cygbicycloalkyl unsubstituted or substituted by methyl, ethyl or CF;

Cs-Ciobicycloalkenyl unsubstituted or substituted by methyl, ethyl or CF;

Ce-Cyobicycloalkadienyl unsubstituted or substituted by methyl, ethyl or CF; , or a group of the form

Ry

NY wherein R7, Rg and Ry are independently of each other C,-Cjalkyl or

R, Ry

C;-Cshaloalkyl; and

Rs and Rg are independently of each other hydrogen, chloro, bromo or fluoro; or

Rs and Rg are independently of each other hydrogen, chloro or fluoro; or

Rs is hydrogen and Rg is chloro or fluoro.

Further preferred subgroups are those wherein a) X is oxygen;

R; is CF;;

R: is C¢-Cgalky! or C1-Csalkoxy-C,-Csalkyl;

Rs is hydrogen or fluoro;

Qis Qf;

Ra is Cg-Cobicycloalkyl unsubstituted or substituted by methyl, ethyl or CF3; or

Ce-Ciobicycloalkenyl unsubstituted or substituted by methyl, ethyl or CF3; or

Ce-Ciobicycloalkadienyl unsubstituted or substituted by methyl, ethyl or CF3; or a group of the form ’ R,

NYY wherein R;, Rg and Ry are independently of each other C;-Csalkyl or

C1-Cshaloalkyl; or a group

Rio ’ haga wherein Ryo and R44 are independently of each other hydrogen or

Rr (CH halogen and n = 1 or 2; and

Rs and Rg are independently of each other hydrogen, fluoro, chloro or bromo; or b) X is oxygen;

Rq is CF3;

R. is C4-Csalkyl or C4-Czhaloalkyl;

Rs; is hydrogen or fluoro;

Qis Q2, Q3 or Q4;

R4 is Ce-Ciobicycloalkyl unsubstituted or substituted by methyl, ethyl or CF3; or

Ce-Cyobicycloalkenyl unsubstituted or substituted by methyl, ethyl or CF;; or

Cs-Cyobicycloalkadienyl unsubstituted or substituted by methyl, ethyl or CF; ; or a group of the form

Rg

NYY wherein R7, Rg and Ry are independently of each other C4-Caalkyl or

R, Ry

C:-Cshaloalkyl; or a group

Rio

Yrs wherein Ry and Ry, are independently of each other hydrogen or

Ro CHa halogen and n = 1 or 2; and

Rs and Rg are independently of each other hydrogen, fluoro, chloro or bromo; and among this subgroup Q = Q2 is preferred; or ab) X is oxygen;

R, is CF3; - ] R:z is methyl or CH,OCHg;

Rs is hydrogen or fluoro; . Qis Qf;

R, is a group of the form g . WO 02/38542 PCT/EP01/12830

Ry : YY wherein R7, Rg and Rg are independently of each other C4-Csalkyl or

R, Ry

Ci-Cshaloalkyl; and

Rs and Rg are independently of each other hydrogen, fluoro, chloro or bromo; or c) X is oxygen;

Ry is CF3;

R. is methyl;

Rs is hydrogen or fluoro;

Qis Qt;

R4 is a group of the form

Ry

YY wherein R7, Rg and Rg are independently of each other CF;, methyl or

R, Ry ethyl, preferably methyl; and

Rs and Rg are independently of each other hydrogen, fluoro or chloro; or d) X is oxygen;

R, is CF3;

Rz is methyl;

Rs is hydrogen;

Qis Qf;

R is a group of the form

Rg

YY wherein R;, Rg and Rg are independently of each other methyl or ethyl,

R, Rg preferably methyl; and

Rs and Rg are independently of each other hydrogen, fluoro or chloro; or ‘ e) X is oxygen;

Ris CF; ’ R; is methyl;

Rs is fluoro;

Qis Q1;

Rs is a group of the form

Re . NOY wherein R;, Rg and Rg are independently of each other methyl or ethyl,

R, Rg preferably methyl; and

Rs and Rg are independently of each other hydrogen, fluoro or chloro.

Other preferred subgroups are those wherein f) X is sulfur;

R; is CF3;

R. is C4-Caalkyl or C4-Cshaloalkyl;

Rs is hydrogen or fluoro;

Qis Q1;

R, is Cg-Cyobicycloalkyl unsubstituted or substituted by methyl, ethyl or CF3; or

Ce-Cyobicycloalkenyl unsubstituted or substituted by methyl, ethyl or CF3; or

Ces-Cyobicycloalkadienyl unsubstituted or substituted by methyl, ethyl or CF;; or a group of the form

Ry

YOY wherein R7, Rg and Rg are independently of each other C4-Cjalkyl or

R, Rg

C4-Cshaloalkyl; or a group

Rio

Ya wherein Rip and Ry are independently of each other hydrogen or

R, (cH), halogen and n = 1 or 2; and

Rs and Rs are independently of each other hydrogen, fluoro, chloro or bromo; or g) X is sulfur,

R, is CF;

R. is C;-Caalkyl or C4-Cghaloalkyl;

Rs is hydrogen or fluoro;

Qis Q2, Q3 or Q4;

R, is Cg-Ciobicycloalkyl unsubstituted or substituted by methyl, ethyl or CF; or

Cs-Ciobicycloalkeny! unsubstituted or substituted by methyl, ethyl or CF3; or

Ce-C1obicycloalkadienyl unsubstituted or substituted by methyl, ethyl or CF3; or a group of the form . fn,

NOY wherein R;, Rg and Ry are independently of each other C;-Csalkyl or - R, Rg

C;-Cshaloalkyl; or a group

Rio hay wherein Ry, and Ry; are independently of each other hydrogen or

RCH halogen and n = 1 or 2; and

Rs and Rg are independently of each other hydrogen, fluoro, chloro or bromo.

Other subgroups of compounds of formula | are those wherein h) X is oxygen or sulfur;

Ri is CF3;

R; is C1-Cjalkyl, C,-Czhaloalkyl or C4-Cjalkoxy-C;-Caalkyl ;

Rs is hydrogen or fluoro;

Qis Qf;

R, is Ce-Cyobicycloalkyl unsubstituted or substituted by methyl, ethyl or CF;

Cs-Cqobicycloalkenyl unsubstituted or substituted by methyl, ethyl or CF;

Cs-C1obicycloalkadienyl unsubstituted or substituted by methyl, ethyl or CF; ; a group of the form

R,

NOY wherein Ry, Rg and Ry are independently of each other C;-Czalkyl or

R, Rg

C;-Cshaloalkyl; and

Rs and Rs are independently of each other hydrogen, chloro or fluoro; or i) X is oxygen or sulfur;

R, is CF3;

R. is C4-Cjalkyl, C1-Cshaloalkyl or C,-Csalkoxy-C+-Csalkyl! ;

Ra is hydrogen or fluoro;

Qis Qt;

Rs is a group of the form

’ © WO 02/38542 PCT/EP01/12830

Ry . YOY wherein R;, Rg and Ry are independently of each other C;-Cjalkyi or

R, Rg ’ C1-Cshaloalkyl; and

Rs and Rg are independently of each other hydrogen, chloro or fluoro; or j) X is oxygen or sulfur;

Riis CF;

R; is C4-Caalkyl, C4-Cshaloalkyl or C,-Cjalkoxy-C4-Cjalkyl;

Rs is hydrogen or fluoro;

Qis Q2, Q3 or Q4;

Rs is Cs-Ciobicycloalkyl unsubstituted or substituted by methyl, ethyl or CF;

Cs-Ciobicycloalkenyl unsubstituted or substituted by methyl, ethyl or CF3;

Ce-Cyobicycloalkadieny! unsubstituted or substituted by methyl, ethyl or CF3; a group of the form

Re

NOY wherein R;, Rg and Rg are independently of each other C4-Caalkyl or

R, Rg

Ci-Cshaloalkyt; and

Rs and Rg are independently of each other hydrogen, chloro or fluoro; or k) X is oxygen or sulfur;

R; is CFy;

R. is C4-Czalkyl, C4-Cshaloalky! or Cy-Csalkoxy-C4-Csalkyi;

Rj is hydrogen or fluoro;

Qis Q2;

R, is Ce-Cigbicycloalkyl unsubstituted or substituted by methyl, ethyl or CFs;

Cs-Ciobicycloalkenyl unsubstituted or substituted by methyl, ethyl or CFs;

Ce-Ciobicycloalkadienyl unsubstituted or substituted by methyl, ethyl or CF3; a group of the form

Ry , NOY wherein Ry, Rg and Rg are independently of each other C4-Cjalkyl or

R, Ry

C4-Cshaloalkyl; and

Rs and Rg are independently of each other hydrogen, chloro or fluoro; or

I) X is oxygen or sulfur; . R; is CH.F or CF.H;

R, is C4-Csalkyl, C;-Cshaloalkyl or C;-Csalkoxy-C4-Caalkyl; : Rs is hydrogen or fluoro;

Qis Qt;

Rs is Ce-Crobicycloalkyl unsubstituted or substituted by methyl, ethyl or CFs;

Ce-C1obicycloalkenyl unsubstituted or substituted by methyl, ethyl or CF;

Ce-Crobicycloalkadienyl unsubstituted or substituted by methyl, ethyl or CF3; a group of the form

Ry

NY wherein R;, Rs and Ry are independently of each other Cy-Caalkyl or

R, Rg

Cy-Cshaloalkyl; and

Rs and Rs are independently of each other hydrogen, chloro or fluoro; or m) X is oxygen;

R, is CHF or CF,H;

R; is methyl or CH,OCHg3;

R; is hydrogen or fluoro;

Qis Q1;

Rs is a group of the form

Ry

NY wherein R;, Rg and Rg are independently of each other C,-Csalkyl or

R, R,

C,-Cshaloalkyl; and

Rs and Rg are independently of each other hydrogen, chloro or fluoro; or n) X is oxygen or sulfur;

R; is CH.F or CF;H; . R. is C1-Csalkyl, C4-Cshaloalkyl or C4-Csalkoxy-C4-Caalkyl;

Rs is hydrogen or fiuoro; . Qis Q2, Q3 or Q4;

R. is Cs-Ciobicycloalkyl unsubstituted or substituted by methyl, ethyl or CF;

Ce-Ciobicycloalkenyl unsubstituted or substituted by methyl, ethyl or CFs;

Cs-Cobicycloalkadienyl unsubstituted or substituted by methyl, ethyl or CF3; a group of the : form

Rg ’ YY wherein Ry, Rs and Rg are independently of each other C,-Csalkyl or

R, Re

C;-Cshaloalkyl; and

Rs and Rs are independently of each other hydrogen, chloro or fluoro; or 0) X is oxygen;

R; is CH.F or CF.H;

R. is methyl or CH,OCHys;

Rs is hydrogen or fluoro;

Qis Q2, Q3 or Q4;

R, is a group of the form

Re wherein R;, Rg and Rg are independently of each other C4-Caalkyl or

R, Rg

C4-Cshaloalkyl; and

Rs and Rs are independently of each other hydrogen, chloro or fluoro.

Preferred individual compounds are : 1-methyl-4-trifluoromethyl-1H-pyrrole-3-carboxylic acid [2-(1,3-dimethylbutyl)phenyl]jamide; 1-methoxymethyl-4-trifluoromethyl-1H-pyrrole-3-carboxylic acid {2-(1,3- dimethylbutyl)phenyilamide; 1-methyl-2-fluoro-4-trifluoromethyl-1H-pyrrole-3-carboxylic acid [2-(1,3- dimethylbutyl)phenyilamide; 1-methoxymethyl-2-fluoro-4-trifluoromethyl-1 H-pyrrole-3-carboxylic acid [2-(1,3- dimethylbutyl)phenyljamide; 1-methyl-4-trifluoromethyl-1H-pyrrole-3-carbothioic acid [2-(1,3-dimethylbutyl)phenyl] amide.

The compounds according to formula | wherein X is oxygen may be prepared according to the following reaction Scheme 1A.

’ v WO 02/38542 PCT/EP01/12830

Scheme 1A . 9 o

R, OOH R, oct HN" R, Q a wv NH ] chiorination | | |]

N base/ solvent N lo R N R, } Rg

R, R, R,

I in | (X=0)

The compounds of the formula | wherein X is oxygen may also be prepared from the corresponding esters according to reaction Scheme 1B.

Scheme 1B 0 MO-alkyl, HO-alkyl 0

R, THF AR

OR (M = Li, Na, K) 1 Ne

EE ——..

IN Q N° "Rr 3 - | 3

R, HN R, v Iv I (X=0) 0°C-reflux

R = G,-Gy-alkyl / t= 15 min. - 24 hours

SiR, (R" = C,-Cg-alkyl)

A further method for the synthesis of compounds of the formula 1 is outlined in Scheme 1C.

Scheme 1C

CHO COOH Q 0

CHO a CHF, P

I 1) "chlorination" I] NH I] NH —————————

N —— eee 2) H,N-Q / base N DAST or SF, N° 1(x=0

R, R -20°C to RT R, R=CHI 2 CH,CI, or CHCI,

The synthesis of the pyrrole carboxylic acids of formula ll wherein Rj; is not hydrogen may be conducted according to Scheme 2A.

Scheme 2A

R, OOH R, OOH 1) 2-3 equi. LDA -78°C /THF

N N

H 2) HP. reagent Eg ] Rs

R, R,

Nn

HY _reagents : 08 N-fluoro-bis(phenylsulfonyl)amine, N-fluoro-N-methyi-toluene-4-sulfonamide, 2-fluoro-3,3-dimethyl-2,3-dihydro-1,2-benzisothiazole-1,1-dioxide, 1-fluoro-sym.-collidiniumtetrafiuoroborate © jn) Mel, MeBr, DMS (dimethylsuifate)

C= NCS, Cl, hexachloroethane

LDA = lithiumdiisopropylamide

The synthesis of the pyrrole carboxylic acids of formula Il wherein Rs = H is described in

WO0-00/09482.

Alternatively the pyrrole carboxylic acid fluorides wherein Rs is fluoro may be obtained as outlined in Scheme 2B.

Scheme 2B

R, OOH 4y2.3 equi LDA/-78°C Fh OOH 2) NCS or Cl, or CI;CCCly —_—

N N" “ci

R, R,

KF / sulfolane COF 100-250°C Ry — || — ———

N° °F

R,

The synthesis of the pyrrole carboxylic acids Il may also be conducted according to the : Schemes 2C or 2D. :

} © WO 02/38542 PCT/EP01/12830

Scheme 2C - co OOR

OR OOH COOR

COOR COOR 1) TOSMIC / base I \ on© A : — _—> N SE — N

H 2) NaH / R,| R, l 2 R,

CH,OH H,F COOR CH,F 1) C-C-C-Cl/ DMF \” OR ? Loon

IN I Ty or Ty 00 NU Te I (Ry=H —_— — — or SOC, N DAST / CH,Cl, N V (Rg=H N R z CHP) 2) NaBH, / THF R, 20°CtoRT R, M=CHP) R, mE

Scheme 2D

COOH LOOR CHO OOR

1) cL / DMF

BD 88 J } yromeas

R, 2) DIBAH or R,

LIAIH(O-t-butyl), -78° - -30°C

THF or hexane

DAST or SF, CF,H OOR CF,H COOH

CH,CL Hydrolysis — = Jy == ['\

N V (RH N Il (Rg=H

R 3= R R,=CHF,) 2 R,=CHF,) 2

The amine intermediates NH,-Q of formula IV may be prepared according to the following reactions as outlined in Scheme 3.

Scheme 3 . Route a) strong base -100 to -110 °C

W-NH-CHO + aketoniX —————> WY-NH-CHO solvent (X) (XI) acid / solvent

NaOH or KOH HN-WY andor HN-Q (IV) in alcohol Pd or Pt on charcoal/ 1) H, / solvent wherein Q, BR, Rg, Ry, Ry, Ry, Ryo, By; and n are as described for the compounds of formula 1,

Hal is Br or I; strong base is n-BuLi, sec.-Buli, tert.-Buli, PhLi; and wherein

R

R R Rs 5

Rs Rs S Re | Se

Wis Wi), — Ss Wa), LD wa) or yp WA

Hal Hal Hal Hal 0] Oo ) IXc

IXis J (H,Me,Et,CF;) R; (IXb) or R; Rio (1Xc)

Oo " Rg Ry Ri (1Xa) n+m=2-10 CH,),

Rg R R R Rs

WY i Re 6 6 (WY10) ,

Is ’ (WY1b)

In Rio

HO (HMe,EtcF) HO Ry HO R,,

R

(WY1a) Im 7 Ry R; (CH,

R

Rs R RoR, Re 6 , (WY2c) ,

SJ wyzp)y , S~Z R

S In HO 10

HO (HMe,EtCF) © Ro & Ru m R 7 (WY2a) ) 7 Ry (CHa),

\ i WO 02/38542 PCT/EP01/12830 i -16 -

R R re 5S R AR WY3 ’ R; 7 ' Rs 7 (WY3b) > _ ( c)

Jn Rio

HO (H,Me,Et,CF,) HO R, HO R ) R R " (WY3a) m TR, 7 (CH),

Rg ) Re Rs s I I wy

R \ ? Rs R ( 4c) ’

In x (WYdb) , 3° Ko R

Va 10

HO (HMeELCE) HO R, HO R.,

R

(WY4a) hn 7 OR, R (CH,), and n+m=2-10 or

Route b) solvent(ether, THF) Pd/C, H,,

MNT xv 0°C to refl FN-WY acid in alcohol HN-QG (V) : 0 reflux oan (Grignard) (Vv) acid, solvent Pd/C, H,, acid in alcohol

HN-TG (Xv) wherein

Rs R

R, R, Rs R; Rg 5 Rg .

Tis (my, 3 (T2) , oo BS (T3) or (T4) 0 0 0 0

R, R, R; R; . Rio

Rg R;; CH,MgHal

XV is = Crtigha or orth ® (XVb) (XVc)

R Re Rs Re Rg Re Rs Re

Ts S S 8 : TG is , _ — , — , — R= R—— Rs : Ry R R

R R 8 9

Rg Ry Rg Ry TG 3b) 9 TG 4b) (TG1b) (TG2b)

Re Rs Re R, Rg Rs Re

Rs S S S ==\ R,, Ri——=— Rio Rr—— Rio Rs - Fao

R; R R,, R,, Ry 1 CH,), (CH,), (TG4c) (CH), ) (CH In C (TG10) 2 (TG2c) (TG3c) and wherein isomeric mixtures are possible at the double bond or

Route c) strong base SOCl, or POC, solvent

NO,W + akelone——Zh > NO,WY —————> NO, TG -105° ridine (xt) (1%) 105°C (Vi) oC to reflux (vim

Raney-Ni /H, — =» HNa (IV) alcohol 50-200 bar/ 50-150°C

Specific amines of the formula IV can be prepared as follows: -- The amines HaN-Q of formula IV, wherein Q = Q1 as defined in formula | and R4 is : bicycloalkyl, bicycloalkenyl or bicycloalkadienyl and Rs and Rg are hydrogen may be obtained according to Scheme 3A (Route a).

Scheme 3A : 2-3 equi. n-BuLi or sec-Buli or other strong bases -100 to -110°C

NHCHO THF/hexane NHCHO 1 _— (4h) )

Br n

HO (H,Me,CF,) (Xa)

H,Me,CF,;) (Xla) © 1Xa n=1-3,m=2 p-TsOH, HCI, H,SO,, NH

NaOH or KOH NH, H,PO, 2 in alcohols > in CH,Cl,, benzene, (Mn ———— toluene, hexane, THF

HO ? 1] (H.Me,CF,) (H,Me,CF,)

Vi Vv

NH,

Pd or Pt on charcoal /H, (Pn (IVa) —————

THF, alcohols H (H.Me,CF,) (exo/endo-isomers for n= 1,2 or 3)

For the synthesis of 2-bicyclo[2.2.1]hept-2-yl phenylamine and other bicyclosystems see for example EP-116044.

According to Scheme 3A the following compounds are also available :

NH, . 0) R

Rio (Ive) Dy starting the 10 reaction sequence Ry,

R R,, 3A with R, CH), Xe 7 (CH), : wherein Rs; and Rg are hydrogen and Ry, Rio, Ry; and n are as defined for formula |.

Ry : -- The amines H.N-Q wherein Q is Q1 and R, is a group of the form ‘ R; Ry

Rs and Rg are hydrogen and Ry, Rg and Ry are as defined for formula | may be obtained according to Scheme 3B (Route b).

Scheme 3B

Rg

NH, _)—CHygHal (excess) NH, 0 R OH Re ® (XVb)

Vi

LS Toon 7 THF or ether, 0°C-reflux 7 R (XIlb)

NH, NH,

He R, Pd,Pt on charcoal / H, R,

CH,CI,, benzene, solvent(THF alcohols) H 0°C - reflux R Ry toluene, hexane, R R I

THF XIv Rs ° IVb + other double bound isomers (other syntheses of ortho-alkylsubstituted anilines are also described in EP-824099) or in a one step hydrogenation of the OH-group of compounds of formula VI

Pd on charcoal / Hy H,S0, vy) ———— IVb alcohols -- Another synthesis of the amine intermediates is outlined in Scheme 3C (Route c).

Scheme 3C

NH, R, for compounds of formula IVb1

Ry

CF, wherein Ry is CF3, Rs and Rg are hydrogen and Rg and Rg are as defined for formula

Rg 1) Strong base OH : THF /-105°C

Br -—_ R 9 2) Coron, CF, (Xi) NO, IXb1 NO, Vila

Oo strong base: n-BuLi, sec-Buli, tert-Buli,

PhLi or others

SOCl, or POC Ry Ry 2 Of 3 Ra-Ni/ H, —_—_— = —_— Ry i Ry pyridine CF, methanol CF, o NO Vii NH IVb1 0°C- reflux 5 150 bar / 100°C ?

E/Z mixture

Using the reaction sequence outlined in Scheme 3C the compounds of formula 1Vc2 wherein Rs and Rg are hydrogen, R; is CF, n=1 and Ry, and Ry; are as defined for formula are also available

NH, Rio +"

CF, Ve2 -- The synthesis of the amines IV wherein Q is Q2, Q3 or Q4, Rs and Rg are hydrogen and

Ry

R, is bicycloalkyl, bicycloalkenyl, bicycloalkadienyl or a group of the form

R; Re and wherein R;, Rg and Rg are as defined for formula | may be obtained according to scheme 3A) or 3B) starting from the following corresponding thienyl derivatives

S

. ZN 57 \ / — or — or or

OHGNH Br OHCNH Br OHCNH Br

S

N

7s ] \ or _ or — o or 0

HN O HN HN

R

R, R; 7 {protected aminothiophenes)

S

OO EEE

BOCNH © BOcNH © BOCNH ©

R, R; R,

BOC = -C(0)OC(CH,), ° Bo x0) and reacting either with the ketone IXa or IXb YY

R, Rg

Re or the Grignard-reagent XVb > CHgha (XVb)

Ry

The present invention also relates to novel ketones of formula IX.

The carbothioic acid amides of formula I, wherein X=S may be obtained from the compounds of formula | wherein X=0 according to Scheme 4.

Scheme 4

R Q 1)Lawesson-Reagent or P,Sg R .Q ! NH 2)Dioxane or THF or toluene ! | NH 0° - reflux 5

LR y Ha | (X=S)

R: 1 x=0) 2 -

The following phenylamine derivatives of formula IV are new and part of the invention : . 2-bicyclo[2.2.2]oct-2-yi-phenylamine; 2-bicyclo[2.2.2]oct-2-en-2-yl-phenylamine; 2-bicyclo[2.2.2]octa-2,5-dien-2-yl-phenylamine; 2-(2-aminophenyl)-1,1,1-trifluoromethyi-4-methyl-pentan-2-ol; 2-(2-aminophenyl)-1-cyclopropyl-propan-2-ol; 2-(2-aminophenyl)-1-cyclopropyl-butan-2-ol; 2-(3-methyl-1-trifluoromethyl-but-1-enyl)-phenylamine; 2-(3-methyl-1-trifluoromethyl-butyl)phenylamine; 2-(2-cyclopropyl-1-methyl-ethyl)phenylamine; and 2-(1-cyclopropylmethyl-propyl)phenylamine.

Surprisingly, it has now been found that the novel compounds of formula | have, for practical purposes, a very advantageous spectrum of activities for protecting plants against diseases that are caused by fungi as well as by bacteria and viruses.

The compounds of formula | can be used in the agricultural sector and related fields of use as active ingredients for controlling plant pests. The novel compounds are distinguished by excellent activity at low rates of application, by being well tolerated by plants and by being environmentally safe. They have very useful curative, preventive and systemic properties and are used for protecting numerous cultivated plants. The compounds of formula | can be used to inhibit or destroy the pests that occur on plants or parts of plants (fruit, blossoms, leaves, stems, tubers, roots) of different crops of useful plants, while at the same time protecting also those parts of the plants that grow later e.g. from phytopathogenic micro- organisms.

It is also possible to use compounds of formula | as dressing agents for the treatment of plant propagation material, in particular of seeds (fruit, tubers, grains) and plant cuttings (e.g. rice), for the protection against fungal infections as well as against phytopathogenic fungi occurring in the soil.

The compounds | are, for example, effective against the phytopathogenic fungi of the following classes: Fungi imperfecti (e.g. Botrytis, Pyricularia, Helminthosporium, Fusarium,

Septoria, Cercospora and Alternaria) and Basidiomycetes (e.g. Rhizoctonia, Hemileia,

Puccinia). Additionally, they are also effective against the Ascomycetes classes (e.g. Ven-

turia and Erysiphe, Podosphaera, Monilinia, Uncinula) and of the Oomycetes classes (e.g. : Phytophthora, Pythium, Plasmopara). Outstanding activity has been observed against powdery mildew (Erysiphe spp.). Furthermore, the novel compounds of formula | are effective against phytopathogenic bacteria and viruses (e.g. against Xanthomonas spp,

Pseudomonas spp, Erwinia amylovora as well as against the tobacco mosaic virus).

Within the scope of present invention, target crops to be protected typically comprise the following species of plants: cereal (wheat, barley, rye, oat, rice, maize, sorghum and related species); beet (sugar beet and fodder beet); pomes, drupes and soft fruit (apples, pears, plums, peaches, almonds, cherries, strawberries, raspberries and blackberries); leguminous plants (beans, lentils, peas, soybeans); oil plants (rape, mustard, poppy, olives, sunflowers, coconut, castor oil plants, cocoa beans, groundnuts); cucumber plants (pumpkins, cucum- bers, melons); fibre plants (cotton, flax, hemp, jute); citrus fruit (oranges, lemons, grapefruit, mandarins); vegetables (spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes, paprika); lauraceae (avocado, cinnamomum, camphor) or plants such as tobacco, nuts, coffee, eggplants, sugar cane, tea, pepper, vines, hops, bananas and natural rubber plants, as well as ornamentals.

The compounds of formula | are used in unmodified form or, preferably, together with the adjuvants conventionally employed in the art of formulation. To this end they are conve- niently formulated in known manner to emulsifiable concentrates, coatable pastes, directly sprayable or dilutable solutions, dilute emulsions, wettable powders, soluble powders, dusts, granulates, and also encapsulations e.g. in polymeric substances. As with the type of the compositions, the methods of application, such as spraying, atomizing, dusting, scatter- ing, coating or pouring, are chosen in accordance with the intended objectives and the pre- vailing circumstances. The compositions may also contain further adjuvants such as stabilizers, antifoams, viscosity regulators, binders or tackifiers as well as fertilizers, micronutrient donors or other formulations for obtaining special effects.

Suitable carriers and adjuvants can be solid or liquid and are substances useful in formula- tion technology, e.g. natural or regenerated mineral substances, solvents, dispersants, wetting agents, tackifiers, thickeners, binders or fertilizers. Such carriers are for example described in WO 97/33890.

The compounds of formula | are normally used in the form of compositions and can be . applied to the crop area or plant to be treated, simultaneously or in succession with further compounds. These further compounds can be e.g. fertilizers or micronutrient donors or other preparations which influence the growth of plants. They can also be selective herbici- des as well as insecticides, fungicides, bactericides, nematicides, molluscicides or mixtures of several of these preparations, if desired together with further carriers, surfactants or application promoting adjuvants customarily employed in the art of formulation.

The compounds of formula | can be mixed with other fungicides, resulting in some cases in unexpected synergistic activities.

Mixing components which are particularly preferred are azoles such as azaconazole, bitertanol, propiconazole, difenoconazole, diniconazole, cyproconazole, epoxiconazole, fluguinconazole, flusilazole, flutriafol, hexaconazole, imazalil, imibenconazole, ipconazole, tebuconazole, tetraconazole, fenbuconazole, metconazole, myclobutanil, perfurazoate, penconazole, bromuconazole, pyrifenox, prochloraz, triadimefon, triadimenol, triflumizole or triticonazole; pyrimidinyl carbinoles such as ancymidol, fenarimol or nuarimol; 2-amino- pyrimidine such as bupirimate, dimethirimol or ethirimol; morpholines such as dodemorph, fenpropidin, fenpropimorph, spiroxamin or tridemorph; anilinopyrimidines such as cyprodinil, pyrimethanil or mepanipyrim; pyrroles such as fenpiclonil or fludioxonil; phenylamides such as benalaxyl, furalaxyl, metalaxyl, R-metalaxyl, ofurace or oxadixyl; benzimidazoles such as benomyl, carbendazim, debacarb, fuberidazole or thiabendazole; dicarboximides such as chlozolinate, dichlozoline, iprodine, myclozoline, procymidone or vinclozolin; carboxamides such as carboxin, fenfuram, flutolanil, mepronil, oxycarboxin or thifluzamide; guanidines such as guazatine, dodine or iminoctadine; strobilurines such as azoxystrobin, kresoxim- methyl, metominostrobin, SSF-129, methyl 2-{(2-trifluoromethyl)-pyrid-6-yloxymethyl}-3- methoxyacrylate or 2-[a{[(a-methyl-3-trifluoromethyl-benzyl)imino]-oxy}-o-tolyl]-glyoxylic acid-methylester-O-methyloxime (trifloxystrobin); dithiocarbamates such as ferbam, mancozeb, maneb, metiram, propineb, thiram, zineb or ziram; N-halomethylthio- ' dicarboximides such as captafol, captan, dichlofluanid, fluoromide, folpet or tolyfluanid; copper compounds such as Bordeaux mixture, copper hydroxide, copper oxychloride, copper sulfate, cuprous oxide, mancopper or oxine-copper; nitrophenol derivatives such as dinocap or nitrothal-isopropyl; organo phosphorous derivatives such as edifenphos, iprobenphos, isoprothiolane, phosdiphen, pyrazophos or toclofos-methyl; and other compounds of diverse structures such as acibenzolar-S-methyl, anilazine, blasticidin-S,

chinomethionat, chloroneb, chlorothalonil, cymoxanil, dichlone, diclomezine, dicloran, . diethofencarb, dimethomorph, dithianon, etridiazole, famoxadone, fenamidone, fentin, ferimzone, fluazinam, fiusulfamide, fenhexamid, fosetyl-aluminium, hymexazol, kasuga- : mycin, methasulfocarb, pencycuron, phthalide, polyoxins, probenazole, propamocarb, pyroquilon, quinoxyfen, quintozene, sulfur, triazoxide, tricyclazole, triforine, validamycin, (S)- 5-methyl-2-methylthio-5-phenyl-3-phenyl-amino-3,5-dihydroimidazol-4-one (RPA 407213), 3,5-dichioro-N-(3-chloro-1-ethyl-1-methyl-2-oxopropyl)-4-methylbenzamide (RH-7281),

N-allyl-4,5-dimethyl-2-trimethylsilylthiophene-3-carboxamide (MON 65500), 4-chloro-4- cyano-N,N-dimethyl-5-p-tolylimidazole-1-sulfon-amide (IKF-216), N-(1-cyano-1,2-dimethyl- propyl)-2-(2,4-dichlorophenoxy)-propionamide (AC 382042), or iprovalicarb (SZX 722).

A preferred method of applying a compound of formula I, or an agrochemical composition which contains at least one of said compounds, is foliar application. The frequency of application and the rate of application will depend on the risk of infestation by the corre- sponding pathogen. However, the compounds of formula | can also penetrate the plant through the roots via the soil (systemic action) by drenching the locus of the plant with a liquid formulation, or by applying the compounds in solid form to the soil, e.g. in granular form (soil application). In crops of water rice such granulates can be applied to the flooded rice field. The compounds of formula | may also be applied to seeds (coating) by impregna- ting the seeds or tubers either with a liquid formulation of the fungicide or coating them with a solid formulation.

The formulation, i.e. the compositions containing the compound of formula | and, if desired, a solid or liquid adjuvant, are prepared in known manner, typically by intimately mixing and/or grinding the compound with extenders, e.g. solvents, solid carriers and, optionally, surface active compounds (surfactants).

The agrochemical formulations will usually contain from 0.1 to 99 % by weight, preferably from 0.1 to 95 % by weight, of the compound of formula I, 99.9 to 1 % by weight, preferably © 99.8105 % by weight, of a solid or liquid adjuvant, and from 0 to 25 % by weight, preferably from 0.1 to 25 % by weight, of a surfactant.

Advantageous rates of application are normally from 5 g to 2 kg of active ingredient (a.i.) per hectare (ha), preferably from 10 g to 1 kg a.i./ha, most preferably from 20 g to 600 g a.i/ha. When used as seed drenching agent, convenient dosages are from 10 mg to 1 g of . active substance per kg of seeds. ‘ Whereas it is preferred to formulate commercial products as concentrates, the end user will normally use dilute formulations.

The following non-limiting examples illustrate the above-described invention in more detail.

Temperatures are given in degrees Celsius. The following abbreviations are used: m.p.= melting point; b.p.= boiling point. "NMR" means nuclear magnetic resonance spectrum. MS stands for mass spectrum. "%" is percent by weight, unless corresponding concentrations are indicated in other units.

Example 1 2-Fluoro-1-methyl-4-trifluoromethyl-1H-pyrrole-3-carboxylic acid

CF, COOH

NF

CH,

A solution of 1.25g (11mmol) lithiumdiisopropylamide (LDA) a 95% in 20ml absolute THF is dropwise added to a solution of 1.0g (5.2mmol) 1-methyl-4-trifluormethyl-1H-pyrrole-3- carboxylic acid in 60mi THF in such a manner that the temperature remains constant at -75°C. After 3 hours stirring at -75°C, a solution of 1.95¢g (6.2mmol) N-fluoro- bis(phenylsulfonyl)amine in 20m! absolute THF is added in ca. 30 minutes at a constant temperature of -75°C. Then the cooling is stopped and the reaction mixture is stirred for 16 hours, thereby slowly warming up to room temperature. Then the solvent is removed in a water jet vacuum and the residue is solved in water. After addition of TN hydrochloric acid (pH = 1) ethylacetate is added and the organic phase extracted twice with additional water. : After separation of the organic phase, drying over sodium sulfate and evaporation of the solvent in a water jet vacuum the raw material is obtained. The crude product is purified by column chromatography over silica-gel (eluant : hexane/ethylacetate = 1:1 )- Yield : 0.65¢g 2-Fluoro-1-methyl-4-trifluoromethyl-1H-pyrrole-3-carboxylic acid in the form of white crystals; m.p. : 190-191°C.

2-Chloro-1-methyi-4-trifluoromethyl-1H-pyrrole-3-carboxylic acid can be obtained in . analogous manner using for example N-chlorsuccinimide as halogenation agent in the reaction described above, m.p. 197-198°C.

Example 2 1-Methyl-4-trifluoromethyl-1H-pyrrole-3-carboxylic acid{2-(1,3-dimethylbutyl)phenyilamide 0 .

CF, a es )

N H,C [cmpd. 1.1]

CH,

H,C

CH,

A solution of 0.5g (2.6mmol) 1-methyl-4-trifuoromethylpyrrole-3-carboxylic acid and 0.37g (2.85mmol) oxalylchloride in 20ml methylene chloride is stirred for 3 hours at room temperature in the presence of a catalytic amount of DMF. Then the acid chloride solution is slowly added to a solution of 0.46g (2.6mmol) 2-(1,3-dimethylbutyl)phenylamine, 0.33g (3.4mmol) triethylamine and 15mi methylene chloride. The resulting mixture is then stirred for 16 hours at room temperature. After removal of the solvent in a water jet vacuum, the raw material is taken up in ethylacetate. The ethylacetate phase is washed twice with water and then the organic phase is dried over sodium sulfate. After evaporation of the solvent in a water jet vacuum, the obtained residue is purified by column chromatography over silica- gel (eluant: hexane/ethylacetate = 3:1). Yield: 0.45g 1-Methyl-4-trifluoromethyl-1H-pyrrole-3- carboxylic acid[2-(1,3-dimethylbutyl)phenyl}amide in the form of brownish crystals; m.p. : 83-85°C.

Example 3 1-Methyl-4-trifluoromethyl-1H-pyrrole-3-carbothioic acid[2-(1,3-dimethylbutyl)phenyllamide

S

CF, ns

N H,C [cmpd. 6.1]

CH,

H,C

CH,

In a sulfonation flask a mixture of 0.6 g 1-Methyl-4-trifluoromethyl-1H-pyrrole-3-carboxylic acid[2-(1,3-dimethylbutyl)phenyljamide, 0.45 g P,Ss and 30 ml dioxane is heated at 70- 75°C for 3 hours. After filtration, the solvent is removed in a water jet vacuum and the residue taken up in ethylacetate. The organic phase is washed twice with water and ethylacetate is removed in a water jet vacuum. The crude material is purified by column chromatography over silica gel (eluant: ethylacetate/n-hexane = 1:1). Yield: 0.53 g 1-Methyl- 4-trifluoromethyl-1H-pyrrole-3-carbothioic acid[2-(1,3-dimethylbutyl)phenyllamide in the form of a reddish resin ('H-NMR).

Example 4 (amine intermediate) 2-(2-cyclopropyl-1-methyi-ethyl)phenylamine

NH, ase

CH, [cmpd. 7.6]

To a solution of 2.96 g (15.5 mmol) of 2-(2-aminophenyl)-1-cyclopropyl-propan-2-ol in 70 mi methanol is added 4.43 g (43.4 mmol) conc. sulfuric acid (96%). The resulting mixture is hydrogenated over 600 mg Pd/C(10%) for 20 hours at 30-35°C. After that time no more hydrogen uptake is detected. The catalyst is filtered off and the solvent removed in a water- jet vacuum. The residue is taken up in ethylacetate/water and the water phase is neutralised by the addition of sodium carbonate. The water phase is extracted twice with ethylacetate, then the combined organic phase is dried over sodium sulfate. After removal of the solvent in a water-jet vacuum, the crude amine is obtained. The obtained raw material is purified by column chromagraphy over silica gel (eluant: hexane/ether = 5:1). Yield: 2.1 g 2-(2-cyclopropyl-1-methyl-ethyl)phenylamine in the form of a brown oil (H-NMR).

Example 5 (amine intermediate) 2-(3-methyl-1-trifluoromethyl-but-1-enyl)phenylamine, E/Z-isomeric mixture : NH, nH cr, Cts [cmpd. 7.4]

i -29 -

A solution of 1.14 g (4.4 mmol) 1-(3-methyl-1-trifluoromethy!-but-1-enyl)-2-nitrobenzene in : 20 ml methanol is hydrogenated over 10% Pd/C (230 mg) at room temperature for 20 minutes. Then the catalyst is filtered off and the solvent removed in a water-jet vacuum. The : crude product is purified by column chromatography over silica gel (eluant: methylenechioride/hexane = 2:1). Yield: 0.6 g((sum E + Z isomer) 2-(3-methyl-1- trifluoromethyl-but-1-enyl)phenylamine in the form of a brown oil. After column chromatography both isomers are obtained in pure form (‘H-NMR).

Example 6 1,1, 1-trifluoromethyl-4-methyl-2-(2-nitrophenyl)-pentan-2-ol

NO, CH,

OH

CF,

To a solution of 20.2 g (0.1 mol) 2-bromonitrobenzene in 300 ml abs. tetrahydrofurane is added 81 ml of sec. BuLi (0.105 mol) over a period of 30 minutes in such a manner that the internal temperature remains constant at —103 to —107°C. After stirring for 70 minutes at — 103 to —107°C a solution of 20.0 g (0.13 mol) of trifluoromethylisobutylketone in 150 mi abs. tetrahydrofurane is added over a period of 20 minutes in such a manner that the temperature remains constant at —105°C (+ 2°C). After stirring for 4 hours at —105°C the temperature is raised to —20°C and a solution of 150 ml of saturated ammoniumchloride solution is added. Then 1 | of ethylacetate is added and the organic phase is washed 3 times with water. After drying the organic phase over sodium sulfate and distilling off the solvent in a water-jet vacuum the raw-material is obtained. Purification is achieved by column chromatography over silica gel (eluant: hexane/ethylacetate = 5:1). Yield: 8.2 g 1,11 -trifluoromethyl-4-methyl-2-(2-nitrophenyl)pentan-2-ol in the form of a brownish powder; m.p.: 103-105°C.

Example 7 ) 1-(8-methyl-1-trifluoromethyl-but-1-enyl)-2-nitrobenzene (E/Z-mixture)

NO, KH a py. CH,

CF, Ch

To a solution of 10.8 g (39 mmol) 1,1,1-trifluoromethyl-4-methyl-2-(2-nitrophenyl)pentan-2-ol : in 110 ml of abs. pyridine is added slowly 13.9 g (117 mmol) thionylchloride at a temperature of 0-5°C. Then the mixture is heated at 90-95°C for 1 hour. After cooling the reaction mixture is added to ice water. The resulting solution is extracted carefully with ethylacetate and after drying of the organic phase over sodium sulfate and distilling off the solvent in a water-jet vacuum, the crude product is obtained. Purification is achieved by column chromatography over silica gel (eluant: methylene chloride/hexane = 1:1). Yield: 5.2 g 1-(3-methyl-1-trifluoromethyl-but-1-enyl)-2-nitrobenzene in the form of a brownish oil ('"H-

NMR).

Example 8 (amine intermediate) 2-(3-methyl-1-trifluoromethyl-butyl)phenylamine

Ne CH,

SA

CF, f[cmpd. 7.5)

A solution of 2.98 g (12.9 mmol) 1-(3-methyl-1-trifluoromethyl-but-1-enyl)-2-nitrobenzene in ml methanol is hydrogenated over Raney-Nickel (ethanol) at 100°C and 150 bar for 10 hours. Then the catalyst is filtered off and the solvent removed in a water-jet vacuum. The obtained crude product is purified by column chromatography over silica gel (eluant: hexane/methylene chloride = 1:2). Yield: 1.9 g 2-(3-methyl-1-triffluoromethyi- butyl)phenylamine in the form of a brown oil (‘H-NMR).

© WO 02/38542 PCT/EP01/12830

Table 1 o Rs : | NA > la : : : (md = mixture of diastereocisomers)

VR, OR i HR,

Re

Cmpd. R; R. Rs Rs R Ry Rs Rs phys. data no. 6 m.p.°C 1.1 CF; Me H H H Me Me Me 83-85 1.2 CF, CH,OMe H H H Me Me Me 75-77 1.3 CF; Me H H H CF; Me Me 98-100 1.4 CF; Me H H H Me CF; CF; 1.5 CF; Me H H H Me Me Et 93-97 (md) 1.6 CF; CHOMe H H H Me Me Et 1.7 CF; Me H 6-F H Me Me Me 1.8 CF; Me H 5F H Me Me Me 1.9 CF; Me H H H Me Et Et 84-86 1.10 CF; Me F H H Me Me Me 1.11 CF, CH,OMe F H H Me Me Me 1.12 CF; Me F H H Me Me Et resin; "H-NMR,

MS

1.13 CF; Me FH H CFs Me Me resin; ‘H-NMR,

MS

1.14 CF; Me F H H CF; Me Et 1.15 CF.H Me H H H Me Me Me . 1.16 CF,H Me H H H Me Me Et 1.17 CF,H Me H H H CF; Me Me Resin : 1.18 CF,H Me H H H Me CF; CF; 1.19 CFH Me H H H CF,H Me Me 1.20 CF,H CH) OMe H H H Me Me Me

1.21 CF,H CH,OMe H H H Me Me Et 122 CRH Me F H H Me Me Me 1.23 CFH Me F H H Me Me Et 1.24 CFH, Me H H H Me Me Me 1.25 CFH, Me H H H Me Me Et 1.26 CFH, Me F H H Me Me Me 1.27 CFH. Me F H H Me Me Et 128 CF; Me H H H Et Me Me Resin; 'H-NMR,

M* = 366 1.29 CF3 Me H H H Et Me Et oil: M" = 380 1.30 CF; Me F H H Et Me Me 1.31 CF; Me F H H Et Me Et 1.32 CFH Me H H H Et Me Me 1.33 CF:H Me H H H Et Me Et 1.34 CF.H Me F H H Et Me Me 1.35 CFH. Me H H H Et Me Me

Table 2 0 Rs

R, 6 A if R, R,

Cmpd. Rj Ro Rs R4 Rs Rs Phys.data no. m.p.°C 2.1 CF; Me H H H

2.2 CF, Me H H H Resin k (H-NMR,

MS) 23 CF; Me H H H y 2.4 CF; Me H H H 136-137 y

CF; Me H 6-F H y 2.6 CF H 3s Me H,C— CH, H H ol H, 27 CF; CH,OMe H H H y 28 CF,H Me H H H

H i WO 02/38542 PCT/EP01/12830 2.9 CF.H Me H H H . H 2.10 CF; Me H H H 105-107 2.11 CF3 Me H H H 110-112 2.12 CF; Me H H H 2.13 CF; Me H H H 127-129 “ H 2.14 CF; CH,OMe H H H

A

2.15 CFs Me H 4-F H / H

216 CF; CH,OMe H 4-F H : / g 247 CFH Me H H H / g 218 CFs Me F H H g 219 CF, Me F H H g g 220 CF; CH.OMe F H H

H

2.21 CF; CH,OMe F H H “ g 222 CF; Me F H H / g

2.23 CF; Me F H H 176-178 / g 2.24 CF; CH,OMe F H H / H 2.25 CF; Me Me H H

H

2.26 CF; Me Me H H / H

Table 3 0] Rs A

R, -

NH NN S lc

R,

N Ry Ry; *o

R, H

Cmpd. R; Ra Rj Rs Rs Ry Rs Ro Phys. data no. m.p.°C 3.1 CFs Me H H H Me Me Me 92-93 3.2 CF; CH,OMe H H H Me Me Me 3.3 CF; Me H H H CFs Me Me 3.4 CF; Me H H H Me CF; CFs 3.5 CF; Me H H H Me Me Et

; vo 7 SLUR UL SAAAT HY FT NEY : rl Jar 11.0¢.°08 11034 LUSSYRGENIH Li HIRO aan’ v4’. Case PF/5-50034A ve -37 - : 36 CFs CHOMe H H H Me Meo Et 3.7 CF, Me H 6F H Me Ms Me ¢ 3.8 CF, Me H B&F H Me Me Ms 3.9 CF, Me H H H Me Et Et 3.10 CF3 Ms F H H Me Me Ms Oil 3.11 CF, CH.OMe F H H Me Me Me 3.12 CF, Me F H H Me Me Et 3.13 CF, Me F H H CFs Me Me 3.14 CFs Me F H H CFa Me Et 3.18 CF:H Me H H H Ms Me Me Qil 3.16 CF:H Me H H H Me Me Eb 3.17 CF.H Me H H H CFs Me Me 3.18 CFH Me H H H Me Me Me 3.19 CFH; Me H H H Me Me Me 3.20 CFH; Me H H H Me Me Et 3.21 CFH, Me H H H CFs Me Me 3.22 CFH: Me H HM H Ms Me Me

Table 4

R, [

R, -

N Ry 4

R,

Cmpd. AR; Ra Rs Rs Rs Rs phys.data no. m.p.°C , 4.1 CF; Me H H H

AMENDED SHEET i WO 02/38542 PCT/EP01/12830 4.2 CF; Me H H ~H Resin 4.3 CF; Me H H H

H

4.4 CF; Me H H H Resin

H

45 CF; Me H 6'-F H

H

4.6 CF, Me H H.C CH, H H ol CH, 47 CF; CH,OMe H H H

H

4.8 CF,H Me H H H } A .

4.9 CFH Me H H H : H 410 CF; Me H H H 4.11 CFs Me H H H 412 CF; Me H H H 413 CFs Me H H H

H

414 CF; CH,OMe H H H

H

415 CF; Me H 4F H / H

4.16 CF; CH.OMe H 4-F H : /H 4.17 CF.H Me H H H ’ H 4.18 CF; Me F H H

H

4.19 CF; Me F H H

H

4.20 CF; CH.OMe F H H

H

H

4.22 CF; Me F H H

4.23 CF; Me F H H : 7 "H 4.24 CF; CH.OMe F H H 7 H 4.25 CF; Me Me H H

H

4.26 CF; Me Me H H 7 H

Table 5 0

R, Rs

NH

R, y

R, R; 2 Ryo

Ry,

Cmpd. Ri R. Rs Rs Rs Ry Rio Ris phys.data no. m.p.°C 5.1 CFs Me H H H Me H H 109-110 5.2 CFs; CH OMe H H H Me H H 5.3 CF; Me H H H CFs H H 54 CF; Me H H H Me Cl Cl 5.5 CF; CH,OMe H H H CF; H H

56 CFs Me F H H Me H H 57 CF, CHOMe F H H Me H H 58 CF; Me F H H CF, H H

59 CF, CHOMe F H H Me H H 510 CFs GCHOMe F H H GCF, H H 511 CFs Me F H H Me C Cl 512 CFH Me H H H Me H H 513 CFH Me H H H CF, H H 514 CFRH CHOMe H H H Me H H 515 CFH CHOMe H H H CFs H H 516 CFH Me F H H Me H H 517 CFH Me F H H CFs H H 518 CFH CH,OMe F H H Me H H 519 CFH CHOMe F H H CFs H H 520 CFH Me H H H Me GC Cl 521 CFH CHOMe H H H Me CI Cl 522 CFH, Me H H H Me H H 523 CFH, Me H H H E H H 524 CFH Me F H H Me H H 525 CF; Me H H H Et H H 5961 526 CF; Me F H H E H H 527 CFH Me H H H Et H H 528 CFH Me F H H Et H H

Table 6

R, i 6 (md = mixture of diastereoisomers) y R, R; 2 HR,

Cmpd. R; Ra Rs: Ry Rs Re Phys. Data no. m.p.°C 6.1 CF; Me H Me Me Me resin; ’H-NMR; M*=368 6.2 CF; CH,OMe H Me Me Me 6.3 CF; Me H CF; Me Me 6.4 CF; Me H Me CF; CF; 6.5 CFs Me H Me Me Et md;resin;'H-NMR;M'=382 6.6 CF; CH,OMe H Me Me Et 6.7 CF; Me H Me Et Et 6.8 CF, Me F Me Me Me Resin; M' = 386 6.9 CF; CH,OMe F Me Me Me 6.10 CF; Me F Me Me Et 6.11 CF; Me F CFs Me Me 6.12 CF; Me F CFs Me Et 6.13 CF.H Me H Me Me Me 6.14 CFH Me H Me Me Et 6.15 CFH Me H CF; Me Me 6.16 CF;H Me H Me Me Me h ‘WO 02/38542 PCT/EP01/12830

Table 7: Amine-Intermediates 71 NH 84-86 2

OH CH,

CH,

CF, 7.2 NH, Oil; "H-NMR a OH /\

CH, 7.3 NH, Oil; "H-NMR a OH /\

C,Hs 7.4 NH, H Oil; "H-NMR 7.4.1: E- : CH, 4.1: py isomer CH, 7.4.2: Z- CFs isomer E/Z-mixture 7.5 NH Oil; "H-NMR 2 CH,

CH,

CF, 7.6 NH, Oil; "H-NMR a H /\

CH, 7.7 NH, Oil; "H-NMR ates

C,H;

"H-NMR Table

Compd. 'H-NMR-data (ppm/multiplicity/number of protons; solvent GDCly) : No. 6.1 0.82/2xd/6H; 1.19/d/3H; 1.35-1.60/m/1H; 3.70/s/3H; 6.99/d/1H; 7.2-7.4/m/4H; 7.61/d/1H; 8.70/s(broad)/1H 6.5 0.75-0.88/m/12H; 1.0-1.65/m/6H; 1.18/d/3H; 1.20/d/3H; 3.0/m/2H; 3.70/s/6H; 7.0/d/2H; 7.2-7.4/m/8H; 7.61/d/2H; 8.7/s/2H 7.2 0.1/m/2H; 0.45/m/2H; 0.65/m/1H; 1.69/s/3H; 1.80/m/1H; 2.0/m/1H,; 3.7/s(broad)/3H(OH+NH;); 6.60-6.70/m/2H; 6.98-7.11/m/2H 7.3 0.01/m/2H; 0.35/m/2H; 0.55/m/2H; 0.75/t/3H; 1.51/m/1H; 1.8-2.05/m/3H; 3.72/s(broad)/3H(OH+NH>); 6.47-6.59/m/2H; 6.91/m/2H 7.41 1.09/d/6H; 3.02/m/1H; 3.60/s(broad)/2H(NH,); 5.81/d/1H; 6.72/m/2H; (E-isomer) 6.99/dxd/1H; 7.15/txd/1H 7.4.2 0.91/d/3H; 1.03/d/3H; 2.25/m/1H; 3.58/s(broad)/2H; 6.36/dxd/1H; (Z-isomer) 6.78/m/2H; 6.99/dxd/1H; 7.18/txd/1H 7.5 0.83/d/3H; 0.87/d/3H; 1.40/m/1H; 1.69/m/1H; 1.99/m/1H; 3.6/m/3H(NH,+H-benzylic); 6.75/dxd/1H; 6.85/t/1H; 7.09-7.2/m/2H 7.6 0.05/m/2H; 0.4/m/2H; 0.69/m/1H; 1.29/d/3H; 1.35/m/1H; 1.60/m/1H; 2.88/m/1H; 3.65/s(broad)/2H(NH,); 6.68/d/1H; 6.85/t/1H; 7.0/txd/1H; 7.1/dxd/1H 7.7 0.01/m/2H; 0.38/m/2H; 0.60/m/1H; 0.82/t/3H; 1.32/m/1H; 1.52-1.80/m/3H; 2.68/m/1H; 3.65/s(broad)/2H(NH); 6.69/d/1H; 6.78/t/1H; 7.0/txd/1H; 7.08/dxd/1H 1.28 0.78-0.85/t+d/9H; 1.35-1.69/m/5H; 2.85/m/1H; 3.70/s/3H; 7.0/d/1H; 7.20/m/3H; 7.37/d/1H; 7.58/s(broad)/1H; 7.7/m/1H

Formulation Examples for compounds of formula

Working procedures for preparing formulations of the compounds of formula | such as

Emuisifiable concentrates, Solutions, Granulates, Dusts and Wettable powders are described in WO 97/33890.

Biological Examples: Fungicidal actions

CT WO 02/38542 PCT/EP01/12830

Example B-1: Action against Puccinia recondita / wheat (Brownrust on wheat) . 1 week old wheat plants cv. Arina are treated with the formulated test compound (0.02% active ingredient) in a spray chamber. One day after application wheat plants are : inoculated by spraying a spore suspension (1 x 10° uredospores/ml) on the test plants.

After an incubation period of 2 days at 20° C and 95% r. h. plants are kept in a greenhouse for 8 days at 20°C and 60% r.h. The disease incidence is assessed 10 days after inoculation.

Compounds of Tables 1 to 6 show good activity in these tests (< 20% infestation).

Example B-2: Action against Podosphaera leucotricha / apple (Powdery mildew on apple) week old apple seedlings cv. Mcintosh are treated with the formulated test compound (0.002% active ingredient) in a spray chamber. One day after application apple plants are inoculated by shaking plants infected with apple powdery mildew above the test plants.

After an incubation period of 12 days at 22° GC and 60% r. h. under a light regime of 14/10 h (light/dark) the disease incidence is assessed.

Compounds of Tables 1 to 6 show good activity in this test.

Example B-3: Action against Venturia inaequalis / apple (Scab on apple) 4 week old apple seedlings cv. Mcintosh are treated with the formulated test compound (0.02% active ingredient) in a spray chamber. One day after application apple plants are inoculated by spraying a spore suspension (4 x 10° conidia/ml) on the test plants. After an incubation period of 4 days at 21° C and 95% r. h. the plants are placed for 4 days at 21° C and 60% r. h. in a greenhouse. After another 4 day incubation period at 21° C and 95% r. h. the disease incidence is assessed.

Compounds of Tables 1 to 6 show good activity in this test.

Example B-4: Action against Erysiphe graminis / barley (Powdery mildew on barley) 1 week old barley plants cv. Express are treated with the formulated test compound (0.02% active ingredient) in a spray chamber. One day after application barley plants are inoculated by shaking powdery mildew infected plants above the test plants. After an incubation period of 6 days at 20° C / 18°C (day/night) and 60% r. h. in a greenhouse the disease incidence is assessed.

Compounds of Tables 1 to 6 show good activity in this test.

47 - a

Example B-5: Action against Botrytis cinerea / apple (Botrytis on apple fruits) : in an apple fruit cv. Golden Delicious 3 holes are drilled and each filled with 30 ul droplets of the formulated test compound (0.002% active ingredient). Two hours after application 50 pl ’ of a spore suspension of B. cinerea (4 x 10° conidia/ml) are pipetted on the application sites. After an incubation period of 7 days at 22° C in a growth chamber the disease incidence is assessed.

Compounds of Tables 1 to 6 show good activity in this test.

Example B-6: Action against Botrytis cinerea / grape (Botrytis on grapes) week old grape seedlings cv. Gutedel are treated with the formulated test compound (0.002% active ingredient) in a spray chamber. Two days after application grape plants are inoculated by spraying a spore suspension (1 x 10° conidia/ml) on the test plants. After an incubation period of 4 days at 21° C and 95% r. h. in a greenhouse the disease incidence is assessed.

Compounds of Tables 1 to 6 show good activity in this test.

Example B-7: Action against Botrytis cinerea / tomato (Botrytis on tomatoes) 4 week old tomato plants cv. Roter Gnom are treated with the formulated test compound (0.002% active ingredient) in a spray chamber. Two days after application tomato plants are inoculated by spraying a spore suspension (1 x 10° conidia/ml) on the test plants. After an incubation period of 4 days at 20° C and 95% r. h. in a growth chamber the disease incidence is assessed.

Compounds of Tables 1 to 6 show good activity in this test.

Example B-8: Action against Pyrenophora teres / barley (Net blotch on barley) 1 week old barley plants cv. Express are treated with the formulated test compound (0.002% active ingredient) in a spray chamber. Two days after application barley plants are inoculated by spraying a spore suspension (3 x 10* conidia/ml) on the test plants. After an incubation period of 2 days at 20° C and 95% r. h. plants are kept for 2 days at 20°C and . 60% r.h. in a greenhouse. The disease incidence is assessed 4 days after inoculation.

Compounds of Tables 1 to 6 show good activity in this test.

Example B-9: Action against Septoria nodorum / wheat (Septoria leaf spot on wheat) : 1 week old wheat plants cv. Arina are treated with the formulated test compound (0.02% active ingredient) in a spray chamber. One day after application wheat plants are ' inoculated by spraying a spore suspension (5 x 10° conidia/mi) on the test plants. After an incubation period of 1 day at 20° C and 95% r. h. plants are kept for 10 days at 20°C and 60% r.h. in a greenhouse. The disease incidence is assessed 11 days after inoculation.

Compounds of Tables 1 to 6 show good activity in this test.

Claims (13)

i WO 02/38542 PCT/EP01/12830 What is claimed is

1. A pyrrolecarboxylic acid amide or pyrrolecarbothioic acid amide of the formula x R, _Q N ) N H H | R, R, wherein X is oxygen or sulfur; R; is CF, CF,H or CFHg;

R. is C4-Cgalkyl, C;-Cshaloalkyl, C;-Csalkoxy-C:-Caalkyl or C;-Cshaloalkoxy-C;-Cjalkyl; Rs is hydrogen, methyl, CF; or fluoro; Rs Rs Re R, Re Re S Rs ] Ss Re . S . Qis @1) , n° @) LS ©, 2 Qa; R} R, R, R, R, is Ce-Cy4bicycloalkyl unsubstituted or substituted by methyl, ethyl or CFs; Ce-C1sbicycloalkenyl unsubstituted or substituted by methyl, ethyl or CF3; Ce-Ci4bicycloalkadienyl unsubstituted or substituted by methyl, ethyl or CF3; a group of the form Ry NY wherein R7, Rg and Rg are independently of each other C;-Casalkyl or R, Re C,-Czhaloalkyl; or a group Rio : Yn, wherein Ry and Ry; are independently of each other hydrogen or R7 (CH, halogen and n = 1 or 2; and Rs and Rs are independently of each other hydrogen or halogen.

2. A compound of formula | according to claim 1, wherein . X is oxygen.

3. A compound of formula | according to claim 1, wherein X is sulfur.

4. A compound of formula | according to claim 1, wherein Ri is CF3; R, is C4-Cjalkyl, C4-Cshaloalkyl or C,-Czalkoxy-C,-Caalkyl ; Rj is hydrogen or fluoro; Qis Qt; R, is C¢-Cyobicycloalkyl unsubstituted or substituted by methyl, ethyl or CF; Ce-Ciobicycloalkenyl unsubstituted or substituted by methyl, ethyl or CF3; Ce-Cypbicycloalkadienyl unsubstituted or substituted by methyl, ethyl or CFs; a group of the form Ry wherein Ry, Rg and Rg are independently of each other C-Cjalkyl or R, Rg C,-Cshaloalkyl; and Rs and Rg are independently of each other hydrogen, chloro or fluoro.

5. A compound of formula I according to claim 4, wherein R, is a group of the form Rg wherein Ry, Rg and Ry are independently of each other C,-Caalkyl or R; Re C,-Cghaloalkyl.

6. A compound of formula | according to claim 1, wherein . Ri is CF3; R; is Cy-Czalkyl, C4-Cghaloalkyl or C,-Csalkoxy-C4-Caalkyl; Rj is hydrogen or fluoro; Qis Q2, Q3 or Q4;

R, is Cs-Ciobicycloalkyl unsubstituted or substituted by methyl, ethyl or CF3; : Ce-Ciobicycloalkenyl unsubstituted or substituted by methyl, ethyl or CF3; Cs-Ciobicycloalkadieny! unsubstituted or substituted by methyl, ethyl or CF3; a group of the form Ry wherein R;, Rg and Ry are independently of each other C-Czalkyl or R, Ry C,-Cshaloalkyl; and Rs and Rs are independently of each other hydrogen, chloro or fluoro.

7. A compound of formula | according to claim 6, wherein Qis Q2.

8. A compound of formula | according to claim 2, wherein R, is CF; R; is C4-Caalkyl or C4-Cjalkoxy-C4-Caalkyl; Rs is hydrogen or fluoro; Qis Qf; Rs is Ce-Ciobicycloalkyl unsubstituted or substituted by methyl, ethyl or GF; Cs-Ciobicycloalkeny! unsubstituted or substituted by methyl, ethyl or CF3; Ces-Ciobicycloalkadienyl unsubstituted or substituted by methyl, ethyl or CF3; a group of the form Ry : YOY wherein Rs, Rg and Ry are independently of each other C,-Csalkyl or R, Rg C,-Cshaloalkyl; or a group Rio . YH, wherein Rio and Ry; are independently of each other hydrogen or A (A halogen and n = 1 or 2; and Rs and Rs are independently of each other hydrogen, chloro or fluoro.

9. A compound of formula | according to claim 8, wherein

> . WO 02/38542 PCT/EP01/12830 R, is methyl or CH,OCHg; R, is a group of the form Ry YOY wherein R;, Rg and Rg are independently of each other CFs, methyl or R, Rs ethyl, preferably methyl; and Rs and Rg are independently of each other hydrogen, fluoro or chloro.

10. A compound of formula I according to claim 9, wherein Rz is methyl.

11. A compound of formula I according to claim 9, wherein Rz is methyl; Rs is hydrogen; R, is a group of the form Re wherein Ry, Rs and Ry are independently of each other methyl or ethyl, R, Rg preferably methyl; and Rs and Rg are independently of each other hydrogen, fluoro or chloro.

12. A compound of formula | according to claim 9, wherein R; is methyf; Rj is fluoro;

R. is a group of the form Re NYY wherein Ry, Rg and Rg are independently of each other methyl or ethyl, R, Rs preferably methyl; and Rs and Rg are independently of each other hydrogen, fluoro or chloro.

13. A compound of formula | according to claim 1, wherein R, is CF2H or CFHy;