BENZOTHIOPHENE DERIVATES AS HERBICIDES

UTILISATION DES DERIVES DU BENZOTHIOPHENE COMME HERBICIDES

English Abstract

Compounds of formula (I) wherein R1 is C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy-
C1-C4alkyl, C1-C4alkoxycarbonyl, cyano, cyano-C1-C4alkyl, hydroxy-C1-C4alkyl,
amino-C1-C4alkyl, CHO, C1-C4alkyl-ON=CH, C2-C6alkenyl, C1-C4alkoxycarbonyl-C2-
C6alkenyl or a group -CH(OR20)OR21; R20 and R21 are each independently of the
other C1-C4alkyl; or R20 and R21 together are -(CH2)n1-; n1 is 2, 3 or 4; R2
is hydrogen or C1-C4alkyl; R3 and R4 are each independently of the other
hydrogen, C1-C4alkyl or halogen; n is 0, 1 or 2; R5 is C1-C4alkyl, C1-
C4haloalkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C4alkoxy, C1-C4haloalkoxy,C1-
C4alkyl-S(O)n2, (C1-C4alkyl)2NS(O)2, C1-C4alkyl-S(O)2O, halogen, nitro or
cyano; n2 is 0, 1 or 2; Q is OH, halogen or a group (Q1), (Q2), (Q3), (Q4),
(Q5), or (Q6); and R6 to R14, W, Y and n6 are as defined in claim 1, and
agrochemically acceptable salts and stereoisomers of those compounds of
formula (I) have good pre- and post-emergence selective herbicidal properties.
The preparation of the compounds and their use as herbicidal active
ingredients are described.

French Abstract

La présente invention concerne les composés de la formule (I) dans laquelle R?1¿ représente C¿1?-C¿4?alkyle, C¿1?-C¿4?haloalkyle, C¿1?-C¿4?alcoxy-C¿1?-C¿4?alkyle, C¿1?-C¿4?alcoxycarbonyle, cyano, cyano-C¿1?-C¿4?alkyle, hydroxy-C¿1?-C¿4?-alkyle, amino-C¿1?-C¿4?-alkyle, CHO, C¿1?-C¿4?-alkyle-ON=CH, C¿2?-C¿6?alcényle, C¿1?-C¿4?alcoxycarbonyle-C¿2?-C¿6?alcényle ou un groupe -CH(OR¿20?)OR¿21?; R¿20? et R¿21? représentent chacun indépendamment l'autre C¿1?-C¿4?alkyle; ou R¿20? et R¿21? représentent ensemble -(CH¿2?)¿n1?-; n¿1? représente 2, 3 ou 4; R¿2? représente un hydrogène ou C¿1?-C¿4?alkyle; R¿3? et R¿4? représentent chacun indépendamment l'autre hydrogène, C¿1?-C¿4?alkyle ou halogène; n représente 0, 1 ou 2; R¿5? représente C¿1?-C¿4?alkyle, C¿1?-C¿4?haloalkyle, C¿2?-C¿6?alcényle, C¿2?-C¿6?alkynyle, C¿1?-C¿4?alcoxy, C¿1?-C¿4?haloalcoxy, C¿1?-C¿4?alkyle-S(O)¿n2?, (C¿1?-C¿4?alkyle)¿2?NS(O)¿2?, C¿1?-C¿4?alkyle-S(O)¿2?O, un halogène, un nitro ou un cyano; n¿2? représente 0, 1 ou 2; Q représente OH, un halogène ou un groupe (Q¿1?), (Q¿2?), (Q¿3?), (Q¿4?), (Q¿5?) ou (Q¿6?); R¿6? à R¿14?, W, Y et n¿6? sont tels que définis dans la revendication 1, les sels et les stéréoisomères acceptables agrochimiquement des composés de la formule (I) possédant de bonnes propriétés herbicides sélectives de pré-levée et de post-levée. Cette invention concerne également la préparation de ces composés et leur utilisation comme ingrédients actifs à action herbicide.

Claims

-101-

What is claimed is:

1. A compound of formula I

Image


wherein
R1 is C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy-C1-C4alkyl, C1-C4alkoxycarbonyl,
cyano,
cyano-C1-C4alkyl, hydroxy-C1-C4alkyl, amino-C1-C4alkyl, CHO, C1-C4alkyl-ON=CH,
C2-C6alkenyl,
C1-C4alkoxycarbonyl-C2-C6alkenyl or a group ~CH(OR20)OR21 ;

R20 and R21 are each independently of the other C1-C4alkyl; or R1 and R2,
together are
-(CH2)n1-;

n1 is 2, 3 or 4;
R2 is hydrogen or C1-C4alkyl;
R3 and R4 are each independently of the other hydrogen, C1-C4alkyl or halogen;
n is 0, 7 or 2;
R5 is C1-C4alkyl, C1-C4haloalkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C4alkoxy, C1-
C4haloalkoxy,
C1-C4alkyl-S(O)n2, (C1-C4alkyl)2NS(O)2, C1-C4alkyl-S(O)2O, halogen, nitro or
cyano;

n2 is 0, 1 or 2;

Q is OH, halogen or a group~Image




-102-

Image


R6 and R7 are each independently of the other hydrogen, OH, C1-C4alkyl, C2-
C6alkenyl,
C2-C6alkynyl, C1-C4alkoxycarbonyl, C1-C4alkyl-S(O)n2, C1-C4alkyl-NHS(O)2,
phenyl or phenyl
substituted by C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy, C1-C4haloalkoxy, C1-
C4alkylcarbonyl,
C1-C4alkoxycarbonyl, amino, C1-C4alkylamino, di-C1-C4alkylamino, C1-C4alkyl-
S(O)n2,
C1-C4alkyl-S(O)2O, C1-C4haloalkyl-S(O)n2, C1-C4haloalkyl-S(O)2O, C1-C4alkyl-
S(O)2NH,
C1-C4alkyl-S(O)2N(C1-C4alkyl), halogen, nitro, COOH or cyano;
or R6 and R7 are each independently of the other C1-C4haloalkyl, -NH-C1-
C4alkyl,
-N(C1-C4alkyl)2, C1-C6alkoxy, cyano, vitro or halogen;
or adjacent R6 and R7 together are -(CH2)n3-;
n3 is 2, 3, 4, 5 or 6;
W is oxygen, sulfur, -C(R18)2- or -N(R22)- ;
n6 is 0 or 1, or when W is -C(R18)2-, n6 may additionally be 2 or 3;
each R18 independently of the other is hydrogen, C1-C4alkyl, C1-C4haloalkyl or
C1-C4alkoxy-carbonyl;
or
R18 together with one of the adjacent substituents R7 forms a single bond when
n6 is 1, and
the remaining geminal R6 and R7 are other than hydrogen;
R22 is hydrogen, C1-C4alkyl or C1-C4alkoxycarbonyl;
R6 is OH, C1-C4alkoxy, C1-C4alkylcarbonyloxy, C1-C4alkoxycarbonyloxy, R23R24N-
C(O)O,
phenylthio, C1-C4alkylthio, C1-C4alkyl-S(O)2O, (C1-C4alkoxy)2P(O)O, C1-
C4alkyl(C1-C4-
alkoxy)P(O)O; H(C1-C4alkoxy)P(O)O or benzoyloxy;
R23 and R24 are each independently of the other hydrogen or C1-C4alkyl;
Y is oxygen, sulfur or -(CH2)n5-;
n5 is 0, 1, 2, 3 or 4;
R9 is hydrogen, C1-C6alkyl, C1-C4alkylcarbonyl, C1-C4alkoxycarbonyl, (C1-
C4alkyl)NHCO or
(C1-C4alkyl)2NCO;



-103-

R10, R11 and R12 are each independently of the others hydrogen, C1-C4alkyl, C1-
C4alkoxy-carbonyl,
phenyl or phenyl substituted by C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy,
C1-C4-haloalkoxy, C1-C4alkylcarbonyl, C1-C4alkoxycarbonyl, amino, C1-
C4alkylamino, di-C1-C4alkyl-amino,
C1-C4alkyl-S(O)n2, C1-C4alkyl-S(O)2O, C1-C4haloalkyl-S(O)n2, C1-C4haloalkyl-
S(O)2O,
C1-C4alkyl-S(O)2NH, C1-C4alkyl-S(O)2N(C1-C4alkyl), halogen, nitro, COOH or
cyano;

R13 is hydrogen; halogen; C1-C4alkyl; C1-C4alkyl substituted by unsubstituted
or
R17-substituted phenyl; C1-C4haloalkyl; C2-C6alkenyl; C2-C6alkenyl substituted
by unsubstituted
or R17-substituted phenyl; C2-C6alkynyl; C2-C6alkynyl substituted by
unsubstituted or
R17-substituted phenyl; C3-C6haloalkenyl; C3-C6haloalkynyl; C3-C6cycloalkyl;
C3-C6cycloalkyl
substituted by halogen, R15 or COOR16; COOR16; COR15; cyano; nitro; CONH2;
(C1-C4-alkyl)NHCO; (C1-C4alkyl)2NCO; (C1-C4haloalkyl)NHCO; (C1-
C4haloalkyl)2NCO; C1-C4alkyl-S(O)n2;
C1-C4alkyl-S(O)n2 substituted by unsubstituted or R17-substituted phenyl;
C1-C4-alkoxy-C2-C6alkyl-S(O)n2; C2-C6alkenyl-S(O)n2; C2-C6alkenyl-S(O)n2
substituted by
unsubstituted or R17-substituted phenyl; C2-C6alkynyl-S(O)n2; or C2-C6alkynyl-
S(O)n2
substituted by unsubstituted or R17-substituted phenyl;

R15 is C1-C4alkyl, C1-C4haloalkyl, C3-C6alkenyl, C3-C6haloalkenyl, C3-
C6alkynyl,
C3-C6haloalkynyl, phenyl or R17-substituted phenyl;

R16 is hydrogen, C1-C4alkyl or C1-C4haloalkyl;

R17 is halogen, C1-C4alkyl, C1-C4haloalkyl, C3-C6alkenyl, C3-C6haloalkenyl, C3-
C6alkynyl,
C3-C6haloalkynyl, C1-C4alkoxy-C1-C4alkyl, C1-C4alkoxy-C3-C6alkenyl, C1-
C4alkoxy-C3-C6-alkynyl,
cyano, nitro, COOH, C1-C4alkoxycarbonyl, C1-C4haloalkoxycarbonyl, C1-C4alkyl-
S(O)n2,
C1-C4haloalkyl-S(O)n2, phenyl-S(O)n2; phenyl-S(O)n2 substituted on the phenyl
ring by
halogen, C1-C4alkyl, C1-C4haloalkyl, C2-C6alkenyl, C3-C6alkynyl, cyano, vitro,
COOH,
C1-C4-alkoxycarbonyl, C1-C4alkyl-S(O)n2, C1-C4haloalkyl-S(O)n2, C1-
C4alkylcarbonyl, di-C1-C4alkyl-amino,
C1-C4alkoxy, C1-C4haloalkoxy, C1-C4alkyl-S(O)2O or C1-C4haloalkyl-S(O)2O;
C1-C4-alkylcarbonyl, di-C1-C4alkylamino, C1-C4alkyl-S(O)2NH, C1-C4alkyl-
S(O)2N(C1-C4alkyl),
C1-C4haloalkyl-S(O)2NH, C1-C4haloalkyl-S(O)2N(C1-C4alkyl), NH2S(O)2, (C1-
C4alkyl)NHS(O)2,
(C1-C4alkyl)2NS(O)2, CONH2, (C1-C4alkyl)NHCO, (C1-C4alkyl)2NCO, NH2CS,
(C1-C4alkyl)NHCS, (C1-C4alkyl)2NCS, C1-C4alkoxy, C1-C4haloalkoxy, C3-
C6alkenyloxy,
C3-C6alkynyloxy, C1-C4alkyl-S(O)2O, C1-C4haloalkyl-S(O)2O, phenyl-S(O)2O or
phenyl-S(O)2O substituted on the phenyl ring by halogen, C1-C4alkyl, C1-
C4haloalkyl, C3-C6alkenyl,
C3-C6alkynyl, cyano, nitro, COOH, C1-C4alkoxycarbonyl, C1-C4alkyl-S(O)n2, C1-
C4haloalkyl-



-104-

S(O)n2, C1-C4alkylcarbonyl, di-C1-C4alkylamino, C1-C4alkoxy, C1-C4haloalkoxy,
C1-C4alkyl-S(O)2O
or C1-C4haloalkyl-S(O)2O; and

R14 is C1-C4alkyl, C1-C4haloalkyl, C3-C6alkenyl, C3-C6haloalkenyl, C3-
C6alkynyl, C3-C6haloalkynyl,
C3-C6cycloalkyl or C3-C6cycloalkyl substituted by halogen, C1-C4alkyl, C1-
C4haloalkyl,
C3-C6alkenyl, C3-C6haloalkenyl, C3-C6alkynyl, C3-C6haloalkynyl, phenyl or
phenyl
substituted by halogen, C1-C4alkyl, C1-C4haloalkyl, C3-C6alkenyl, C3-
C6alkynyl, cyano, nitro,
COOH, C1-C4alkoxycarbonyl, C1-C4alkyl-S(O)n2, C1-C4haloalkyl-S(O)n2, C1-
C4alkylcarbonyl,
di-C1-C4alkylamino, C1-C4alkoxy, C1-C4haloalkoxy, C1-C4alkyl-S(O)2O or C1-
C4haloalkyl-S(O)2O,

or an agrochemically acceptable salt or a stereoisomer of such a compound of
formula 1.

2. A compound according to claim 1, wherein R1 is C1-C4alkyl, C1-C4haloalkyl,
C1-C4alkoxy-C1-C4alkyl,
C1-C4alkoxycarbonyl, cyano, cyano-C1-C4alkyl, CHO, C1-C4alkyl-ON=CH,
C2-C6alkenyl, C1-C4alkoxycarbonyl-C2-C6alkenyl or a group -CH(OR20)OR21;
W is oxygen, sulfur, -C(R15)2- or -N(R22)-; each R18 independently of the
other is hydrogen,
C1-C4alkyl or C1-C4alkoxycarbonyl; and R22 is hydrogen, C1-C4alkyl or C1-
C4alkoxycarbonyl.

3. A process for the preparation of a compound of formula I

Image



-105-

wherein R1 to R5 and n are as defined in claim 1; Q is a group

Image R8 is OH; and R6,

R7, R9, R10, W, n6 and Y are as defined in claim 1, which comprises either
a) reacting a compound of formula III
Image
wherein R1 to R5 and n are as defined and X is a leaving group, in an inert
organic solvent
in the presence of a base with a compound of formula IV

Image
wherein
Z1 is C(R6)R7, Z2 is (W)n6, Z3 is C(R6)R7 and n4 is 0 (= group Q1);
Z1 is CH, Z2 is oxygen, sulfur or -(CH2)n5- (=Y), Z3 is CH and n4 is 2 (=
group Q2);
Z, is CH2, Z2 is CHNHR9, Z3 is CH2 and n4 is 0 (= group Q3); or
Z, is NR10, Z2 is oxygen, Z3 is C(R6)R7 and n4 is 0 (= group Q4),
and R6, R7, R9, R10, W, n6 and n5 are as defined in claim 1, to form a
compound of
formula Ic



-106-

Image
and then isomerising that compound; or
b) reacting a compound of formula Id
Image
wherein R1 to R5 and n are as defined, with a compound of formula IV
Image
wherein Z1, Z2, Z3 and n4 are as defined, in an inert organic solvent in the
presence of a
base and a coupling agent to form a compound of formula Ic
Image
and then isomerising that compound.



-107-

4. A compound of formula V
Image
wherein R1 to R5, R14 and n are as defined in claim 1.

5. A compound of formula VII

Image
wherein R1 to R5, R14 and n are as defined in claim 1; R25 is C1-C4alkyl, C1-
C4alkyl
substituted by unsubstituted or R17-substituted phenyl, C1-C4alkoxy-C2-
C6alkyl, C2-C6alkenyl,
C2-C6alkenyl substituted by unsubstituted or R17-substituted phenyl, C2-
C6alkynyl or
C2-C6-alkynyl substituted by unsubstituted or R17-substituted phenyl; R17 is
halogen, C1-C4alkyl,
C1-C4haloalkyl, C3-C6alkenyl, C3-C6haloalkenyl, C3-C6alkynyl, C3-
C6haloalkynyl, C1-C4alkoxy-
C1-C4alkyl, C1-C4alkoxy-C3-C6alkenyl, C1-C4alkoxy-C3-C6alkynyl, cyano, vitro,
COOH,
C1-C4alkoxycarbonyl, C1-C4haloalkoxycarbonyl, C1-C4alkyl-S(O)n2, C1-
C4haloalkyl-S(O)n2,
phenyl-S(O)n2; phenyl-S(O)n2 substituted on the phenyl ring by halogen, C1-
C4alkyl,
C1-C4-haloalkyl, C3-C6alkenyl, C3-C6alkynyl, cyano, nitro, COOH, C1-
C4alkoxycarbonyl, C1-C4alkyl-S(O)n2,
C1-C4haloalkyl-S(O)n2, C1-C4alkylcarbonyl, di-C1-C4alkylamino, C1-C4alkoxy,
C1-C4-haloalkoxy, C1-C4alkyl-S(O)2O or C1-C4haloalkyl-S(O)2O; C1-
C4alkylcarbonyl, di-C1-C4alkyl-amino,
C1-C4alkyl-S(O)2NH, C1-C4alkyl-S(O)2N(C1-C4alkyl), C1-C4haloalkyl-S(O)2NH,
C1-C4-haloalkyl-S(O)2N(C1-C4-alkyl), NH2S(O)2, (C1-C4alkyl)NHS(O)2, (C1-
C4alkyl)2NS(O)2, CONH2,
(C1-C4alkyl)NHCO, (C1-C4alkyl)2NCO, NH2CS, (C1-C4alkyl)NHCS, (C1-C4alkyl)2NCS,

C1-C4-alkoxy, C1-C4haloalkoxy, C3-C6alkenyloxy, C3-C6alkynyloxy, C1-C4alkyl-
S(O)2O, C1-C4halo-
alkyl-S(O)2O, phenyl-S(O)2O or phenyl-S(O)2O substituted on the phenyl ring by
halogen,
C1-C4alkyl, C1-C4haloalkyl, C3-C6alkenyl, C3-C6alkynyl, cyano, nitro, COOH, C1-
C4alkoxy-carbonyl,
C1-C4alkyl-S(O)n2, C1-C4haloalkyl-S(O)n2, C1-C4alkylcarbonyl, di-C1-
C4alkylamino,



-108-

C1-C4alkoxy, C1-C4haloalkoxy, C1-C4alkyl-S(O)2O or C1-C4haloalkyl-S(O)2O; and
n2 is 0, 1
or 2.

6. A compound of formula IX
Image
wherein R1 to R5, R14 and n are as defined in claim 1; R13 is hydrogen, C1-
C4alkyl, C1-C4alkyl
substituted by unsubstituted or R17-substituted phenyl, C1-C4haloalkyl, C2-
C6alkenyl,
C2-C6-alkenyl substituted by unsubstituted or R17-substituted phenyl, C2-
C6alkynyl, C2-C6alkynyl
substituted by unsubstituted or R17-substituted phenyl, C3-C6haloalkenyl, C3-
C6haloalkynyl,
C3-C6cycloalkyl or C3-C6cycloalkyl substituted by halogen, R15 or COOR16; R17
is halogen,
C1-C4alkyl, C1-C4haloalkyl, C3-C6alkenyl, C3-C6haloalkenyl, C3-C6alkynyl, C3-
C6haloalkynyl,
C1-C4alkoxy-C1-C4alkyl, C1-C4alkoxy-C3-C6alkenyl, C1-C4alkoxy-C3-C6alkynyl,
cyano, nitro,
COOH, C1-C4alkoxycarbonyl, C1-C4haloalkoxycarbonyl, C1-C4alkyl-S(O)n2, C1-
C4haloalkyl-S(O)n2,
phenyl-S(O)n2; phenyl-S(O)n2 substituted on the phenyl ring by halogen, C1-
C4alkyl,
C1-C4haloalkyl, C3-C6alkenyl, C3-C6alkynyl, cyano, nitro, COOH, C1-
C4alkoxycarbonyl,
C1-C4alkyl-S(O)n2, C1-C4haloalkyl-S(O)n2, C1-C4alkylcarbonyl, di-C1-
C4alkylamino,
C1-C4alkoxy, C1-C4haloalkoxy, C1-C4alkyl-S(O)2O or C1-C4haloalkyl-S(O)2O; C1-
C4alkyl-carbonyl,
di-C1-C4alkylamino, C1-C4alkyl-S(O)2NH, C1-C4alkyl-S(O)2N(C1-C4alkyl),
C1-C4-haloalkyl-S(O)2NH, C1-C4haloalkyl-S(O)2N(C1-C4alkyl), NH2S(O)2, (C1-
C4alkyl)NHS(O)2,
(C1-C4alkyl)2NS(O)2, CONH2, (C1-C4alkyl)NHCO, (C1-C4alkyl)2NCO, NH2CS, (C1-
C4alkyl)-NHCS,
(C1-C4alkyl)2NCS, C1-C4alkoxy, C1-C4haloalkoxy, C3-C6alkenyloxy, C3-
C6alkynyloxy,
C1-C4alkyl-S(O)2O, C1-C4haloalkyl-S(O)2O, phenyl-S(O)2O or phenyl-S(O)2O
substituted on
the phenyl ring by halogen, C1-C4alkyl, C1-C4haloalkyl, C3-C6alkenyl, C3-
C6alkynyl, cyano,
nitro, COOH, C1-C4alkoxycarbonyl, C1-C4alkyl-S(O)n2, C1-C4haloalkyl-S(O)n2, C1-
C4alkyl-carbonyl,
di-C1-C4alkylamino, C1-C4alkoxy, C1-C4haloalkoxy, C1-C4alkyl-S(O)2O or C1-
C4halo-
alkyl-S(O)2O; n2 is 0, 1 or 2; R15 is C1-C4alkyl, C1-C4haloalkyl, C3-
C6alkenyl,
C3-C6-haloalkenyl, C3-C6alkynyl, C3-C6haloalkynyl, phenyl or R17-substituted
phenyl; R16 is
hydrogen, C1-C4alkyl or C1-C4haloalkyl; and R27 is C1-C4alkyl.



-109-



7. A herbicidal and plant-growth-inhibiting composition comprising a
herbicidally effective
content of a compound of formula I, and an inert carrier.
8. A method of controlling undesired plant growth, wherein a compound of
formula I, or a
composition comprising such a compound, is applied in a herbicidally effective
amount to
the crops of useful plants or to the locus thereof.
9. The use of a composition according to claim 7 in controlling undesired
plant growth.

Description

CA 02291101 1999-11-24
WO 99/09023 - 1 - PCT/EP98/05247
BENZOTHIOPHENE DERIVATES AS IWRBICIDES
The present invention relates to novel herbicidally active substituted
bicyclic benzoyl
derivatives, to processes for the preparation thereof, to compositions
comprising those
compounds, and to the use thereof in the control of weeds, especially in crops
of useful
plants, for example cereals, maize, rice, cotton, soybeans, rape, sorghum,
sugar cane,
sugar beet, sunflowers, vegetables, plantation crops and fodder plants, or in
the inhibition of
plant growth.
Isoxazolyl- and pyrazolyl-benzoyl and bicyclic benzoyl derivatives having
herbicidal activity
are known and are described, for example, in WO 96/26192, WO 96/26206 and
W O 97/08164.
New substituted bicyclic benzoyl derivatives having herbicidal and growth-
inhibiting
properties have now been found.
The present invention therefore relates to compounds of formula I
R~
R2 S(O)n O
Ra ~ C.Q
R4
Rs
wherein
R, is C,-C4alkyl, C,-C4haloalkyl, C,-Caalkoxy-C,-C4alkyl, C,-C4alkoxycarbonyl,
cyano, cyano-
C,-C4alkyl, hydroxy-C,-C4alkyl, amino-C,-C,alkyl, CHO, C,-C4alkyl-ON=CH, C2-
Csalkenyl,
C,-C4alkoxycarbonyl-C2-Cealkenyl or a group -CH(OR2o)OR2, ;
Rzo and R2, are each independently of the other C,-C4alkyl; or R~ and R2,
together are
-(CH2)",-~
n, is 2, 3 or 4;
R2 is hydrogen or C,-C4alkyl;
R3 and R4 are each independently of the other hydrogen, C,-Caalkyl or halogen;
n is 0, 1 or 2;


CA 02291101 1999-11-24
WO 99/09023 - 2 - PCT/EP98/05247
R5 is C1-C4alkyl, Ct-C4haloalkyl, Cz-Csalkenyl, Cz-Csalkynyl, C,-C4alkoxy, C,-
C4haloalkoxy,
C,-C,alkyl-S(O)"z, (C,-C4alkyl)zNS(O)z, C,-Caalkyl-S(O)z0, halogen, vitro or
cyano;
nz is 0, 1 or 2;
O
Rs Re
Q is OH, halogen or a group ~ W~ ~ (Q,), Y {Qz),
Ra ~ ns n
Rs R7
O ~ Rs R"
{Qs), / ~ R~ {Q4)~ OH ' N\N {QS) or
Ra NH~R9 O
,o ,z
R, a
I \ N (Gls);
R'4 O,
Rs and R~ are each independently of the other hydrogen, OH, C,-C4alkyl, Cz-
Csalkenyl,
Cz-Csalkynyl, C,-C4alkoxycarbonyl, C~-C4alkyl-S(O)~z, C,-C4alkyl-NHS(O)2,
phenyl or phenyl
substituted by C,-C4alkyl, C,-C4haloalkyl, C,-C4alkoxy, C,-C4haloalkoxy, C,-
C4alkyicarbonyl,
C,-C4aikoxycarbonyl, amino, C,-C4alkylamino, di-C,-C4aikylamino, C,-C4alkyl-
S(O)"z,
C,-Caalkyl-S(O)z0, C,-Cahaioalkyl-S(O)~z, C,-C4hafoalkyl-S(O)z0, C,-Caalkyl-
S(O)zNH,
C,-C4alkyl-S(O)zN(C,-C4alkyl), halogen, vitro, COOH or cyano;
or Rs and R~ are each independently of the other C,-Cahaloaikyl, -NH-C,-
C4alkyl,
-N(C,-Caalkyl)z, C,-Csalkoxy, cyano, vitro or halogen;
or adjacent Rs and R~ together are -(CHz)~3-;
n3 is 2, 3, 4, 5 or fi;
W is oxygen, sulfur, -C{R,e)z- or -N(Rzz)- ;
ns is 0 or 1, or when W is -C(R,8)z- , ns may additionally be 2 or 3;
each R,s independently of the other is hydrogen, C,-C4alkyl, C,-C,haloalkyl or
C,-C4alkoxy-
carbonyl; or


CA 02291101 1999-11-24
WO 99!09023 - 3 - PCT/EP98/05247
R,8 together with one of the adjacent substituents R~ forms a single bond when
ns is 1, and
the remaining geminal Rs and R, are other than hydrogen;
Rzz is hydrogen, C,-C4alkyl or C,-Cealkoxycarbonyl;
Re is OH, C,-C4alkoxy, C,-C4alkylcarbonyloxy, C,-Caalkoxycarbonyloxy, Rz3Rz4N-
C{O)O,
phenylthio, C,-Caalkylthio, C,-C4alkyl-S(O)z0, (C,-C4alkoxy)zP(O)O, C,-
C4alkyl(C,-C4-
alkoxy)P(O)O, H(C,-C4alkoxy)P(O)O or benzoyloxy;
Rz3 and Rza are each independently of the other hydrogen or C,-Coalkyl;
. Y is oxygen, sulfur or -(CHz)"s-;
ns is 0, 1, 2, 3 or 4;
R9 is hydrogen, C,-Cealkyl, C,-C4alkylcarbonyl, C,-Caalkoxycarbonyl, (C,-
C4alkyl)NHCO or
(C,-C4alkyl)zNCO;
R,o, R" and R,z are each independently of the others hydrogen, C,-C4alkyl, C,-
C4alkoxy-
carbonyl, phenyl or phenyl substituted by C,-C4alkyl, C,-C4haloalkyl, C,-
C4alkoxy, C,-C4-
haloaikoxy, C,-Caalkylcarbonyl, C,-Coalkoxycarbonyl, amino, C,-Caalkylamino,
di-C,-C4alkyl-
amino, C,-Caalkyl-S(O)~z, C,-C,alkyl-S(O)z0, C,-C4haloalkyl-S(O)"z, C,-
C4haloalkyi-S(O)zO,
C,-C4alkyl-S(O)zNH, C,-C4alkyl-S(O)zN(C,-C4alkyl), halogen, vitro, COOH or
cyano;
R,3 is hydrogen; halogen; C,-C4alkyl; C,-Caalkyl substituted by unsubstituted
or R"-
substituted phenyl; C,-C,,haioalkyl; Cz-Csaikenyl; Cz-Csalkenyl substituted by
unsubstituted
or R,~-substituted phenyl; Cz-Csalkynyl; Cz-Csalkynyl substituted by
unsubstituted or R"-
substituted phenyl; C3-Cghaloalkenyl; C3-Cehaloalkynyl; C3-Cecycloalkyl; C3-
Cecycloalkyl
substituted by halogen, R,s or COOR,6; COOR,6; COR,s; cyano; vitro; CONHz; (C,-
C4-
alkyl)NHCO; (C,-C4alkyl)zNCO; (C,-C4haloalkyl)NHCO; (C,-C4haloalkyi)zNCO; C,-
C4alkyl-
S(O)~z; C,-C4alkyl-S(O)~z substituted by unsubstituted or R"-substituted
phenyl; C,-C4-
alkoxy-C2-CBalkyl-S(O)~2; C2-Csalkenyl-S(O)~z; Cz-Cgalkenyl-S(O)nz substituted
by
unsubstituted or R"-substituted phenyl; Cz-Csalkynyl-S(O)"z; or Cz-Csalkynyl-
S(O)"z
substituted by unsubstituted or R,~-substituted phenyl;
R,s is C,-C4alkyl, C,-C4haloalkyl, C3-Csalkenyl, C3-Cshaloalkenyl, C3-
Csalkynyl, C3-Cshalo-
alkynyl, phenyl or R"-substituted phenyl;
R,e is hydrogen, C,-C4alkyl or C,-C4haloaikyl;
R,~ is halogen, C,-C4alkyl, C,-C4haloalkyl, C3-Cealkenyl, C3-Cehaloaikenyl, C3-
Csalkynyl,


CA 02291101 1999-11-24
WO 99109023 - 4 - PCT/EP98/05247
C3-Cshaloalkynyl, C,-C4alkoxy-C,-Cdalkyl, C,-C4alkoxy-Ca-Csalkenyl, C,-
C4alkoxy-C3-Cs-
alkynyl, cyano, nitro, COOH, C,-C4alkoxycarbonyl, C,-C4haloalkoxycarbonyl, C,-
C4alkyl-
S(O)~2, C,-Cahaloalkyl-S{O)~2, phenyl-S(O)n2; phenyl-S(O)~2 substituted on the
phenyl ring by
halogen, C,-C4alkyl, C,-C4haloalkyl, C3-Csalkenyl, C3-Csalkynyl, cyano, nitro,
COOH, C,-C4-
alkoxycarbonyl, C,-Caalkyl-S(O)~2, C,-C4haloalkyl-S(O)n2, C,-Caalkytcarbonyl,
di-C,-C4alkyt-
amino, C,-C4alkoxy, C1-C4haloalkoxy, C,-C4alkyl-S{O)20 or C,-C4haloalkyl-
S(O)20; C,-C4-
aikylcarbonyl, di-C,-Caalkylamino, C,-C4alkyl-S(O)2NH, C,-C4alkyl-S(O)2N{C,-
C4alkyl),
C,-Cahaloalkyl-S(O)2NH, C,-C4hatoalkyl-S(O)2N(C,-Cealkyl), NH2S(O)2, (C,-
C4alkyl)NHS(O)2,
(C,-C4alkyl)2NS(O)2, CONH2, (C,-Caalkyl)NHCO, (C,-C4alkyl)2NC0, NH2CS,
(C,-C4alkyl)NHCS, (C,-C4alkyl)2NCS, C,-C4alkoxy, C1-C4haloalkoxy, C3-
Csaikenyloxy,
C3-Csalkynyloxy, C,-C4alkyl-S(O)20, C,-Cahaloalkyl-S(O)20, phenyl-S(O)20 or
phenyl-
S(O)20 substituted on the phenyl ring by halogen, C,-C4alkyl, C,-C4haloalkyl,
C3-Csalkenyl,
C3-Csalkynyl, cyano, vitro, COOH, C,-C4alkoxycarbonyl, C,-Caalkyl-S(O)~2, C,-
C4haloalkyl-
S(O)~2, C,-Caalkylcarbonyl, di-C,-C4alkylamino, C,-C4alkoxy, C,-C4haloalkoxy,
C,-C4alkyl-
S{O)20 or C,-C4haloatkyl-S(O)20; and
R,4 is C,-C4alkyl, C,-C4haloalkyl, C3-Csalkenyl, C3-Cshaloalkenyl, C3-
Csalkynyl, C3-Cshalo-
alkynyl, C3-Cscycloalkyl or C3-Cgcycloalkyl substituted by halogen, C~-
Caalkyl, C,-Cahalo-
alkyl, C3-Csalkenyl, C3-Cshaloalkenyl, C3-Csalkynyl, C3-Cshaloalkynyl, phenyl
or phenyl
substituted by halogen, C,-C4alkyl, C,-C4haloalkyl, C3-Csalkenyl, C3-
Csalkynyl, cyano, vitro,
COOH, C,-Caalkoxycarbonyl, C,-C4atkyl-S(O)"2, C,-C4haloalkyl-S(O)~2, C,-
C4alkylcarbonyl,
di-C,-C4alkylamino, C,-C4alkoxy, C,-C4haloalkoxy, C,-C4alkyl-S(O)20 or C,-
C4haloalkyl-
S(O)20,
and the agrochemically acceptable salts and stereoisomers of those compounds
of
formula I.
In the above definitions, halogen is to be understood as meaning iodine or,
preferably,
fluorine, chlorine or bromine.
The alkyl, alkenyl and alkynyl groups in the substituent definitions may be
straight-chain or
branched, this applying also to the alkyl, alkenyl and alkynyi moiety of the
following groups:
alkylcarbonyl, cyanoalkyl, alkoxyalkyl, alkyfthio, alkylsulfonyl,
alkylaminocarbonyl, dialkyl-
aminocarbonyl, (alkyl)2NS(O)2, alkyl(alkoxy)P{O)O, alkyl substituted by
unsubstituted or R"-
substituted phenyl, alkenyl substituted by unsubstituted or R"-substituted
phenyl, alkoxy-
carbonylalkenyl, aIkyIS(O}2N(alkyl), (alkyl)2NC0, (alkyl)2NCS ,alkenyl-S{O)~2
substituted by


CA 02291101 1999-11-24
WO 99/09023 - 5 - PCT/EP98I05247
unsubstituted or R,~-substituted phenyl, alkoxyalkenyl, alkenyloxy and
alkynyloxy.
Alkyl groups are, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl,
sec-butyl, isobutyl,
tert-butyl and the various isomers of pentyl and hexyl. Methyl, ethyl, n-
propyl, isopropyl and
n-butyl are preferred.
Examples of alkenyl radicals that may be mentioned are vinyl, ally!,
methallyl, 1-methylvinyl,
but-2-en-1-yl, pentenyl and 2-hexenyl, with preference being given to alkenyl
radicals
having a chain length of from 3 to 5 carbon atoms.
Examples of alkynyl radicals that may be mentioned are ethynyl, propargyl, 1-
methyl-
propargyl, 3-butynyl, but-2-yn-1-yl, 2-methylbut-3-yn-2-yl, but-3-yn-2-yl, 1-
pentynyl, pent-4-
yn-1-yl and 2-hexynyl, with preference being given to alkynyl radicals having
a chain length
of from 2 to 4 carbon atoms.
Suitable haloalkyl radicals are alkyl groups that are mono- or poly-
substituted, especially
mono- to tri-substituted, by halogen, halogen being in particular iodine or
especially fluorine,
chlorine or bromine, for example fluoromethyl, difluoromethyl,
trifiuoromethyl, chloromethyl,
dichloromethyl, trichloromethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2-
chloroethyl, 2,2-dichloro-
ethyl, 2,2,2-trifluoroethyl and 2,2,2-trichloroethyl.
Suitable haloalkenyl radicals are alkenyl groups mono- or poly-substituted by
halogen,
halogen being in particular bromine, iodine or especially fluorine or
chlorine, for example 2-
or 3-fluoropropenyl, 2- or 3-chioropropenyl, 2- or 3-bromopropenyl, 2,3,3-
trifluoropropenyl,
2,3,3-trichloropropenyl, 4,4,4-trifluorobut-2-en-1-yl and 4,4,4-trichlorobut-2-
en-1-yl. Of the
alkenyl radicals mono-, di- or tri-substituted by halogen, preference is given
to those having
a chain length of 3 or 4 carbon atoms. The alkenyl groups may be substituted
by halogen at
saturated or unsaturated carbon atoms.
Suitable haloalkynyl radicals are, for example, alkynyl groups mono- or poly-
substituted by
halogen, halogen being bromine, iodine or especially fluorine or chlorine, for
example 3-
fluoropropynyl, 3-chloropropynyl, 3-bromopropynyl, 3,3,3-trifluoropropynyl and
4,4,4-
trifluoro-but-2-yn-1-yl.
Alkylsulfonyl is, for example, methylsulfonyl, ethylsulfonyl, propylsulfonyl,
isopropylsulfonyl,
n-butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl, tart-butylsulfonyl or an
isomer of pentyl-


CA 02291101 1999-11-24
WO 99/09023 - s - PCT/EP98I05247
sulfonyl or hexylsulfonyl; preferably methylsulfonyl or ethylsulfonyl.
Haloalkylsulfonyl is, for example, fiuoromethyisulfonyl,
difluoromethylsulfonyl, trifluoro-
methylsulfonyl, chloromethylsulfonyl, trichloromethylsulfonyl, 2-
fluoroethylsulfonyl, 2,2,2-tri-
fluoroethylsulfonyl or 2,2,2-trichloroethylsulfonyl.
Alkenylsulfonyl is, for example, allylsulfonyl, methallylsulfonyl, but-2-en-1-
ylsulfonyl,
pentenylsulfonyl or 2-hexenylsulfonyl.
Cyanoalkyl is, for example, cyanomethyl, cyanoethyl, cyanoeth-1-yl or
cyanopropyl.
Alkylamino is, for example, methylamino, ethyfamino or an isomer of propyl- or
butyl-amino.
Dialkylamino is, for example, dimethylamino, diethylamino or an isomer of
dipropyl- or
dibutyl-amino.
Alkylcarbonyl is especially acetyl or propionyl.
Alkoxy is, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy,
isobutoxy, sec-
butoxy or tert-butoxy.
Alkenyloxy is, for example, allyloxy, methallyioxy or but-2-en-1-yloxy.
Aikynyloxy is, for example, propargyloxy or 1-methylpropargyloxy.
Alkoxyalkyl is, for example, methoxymethyf, methoxyethyl, ethoxymethyl,
ethoxyethyl,
n-propoxymethyl, n-propoxyethyl, isopropoxymethyl or isopropoxyethyi.
Alkoxycarbonyl is, for example, methoxycarbonyl, ethoxycarbonyl, n-
propoxycarbonyl, iso-
propoxycarbonyl or n-butoxycarbonyl, preferably methoxycarbonyl or
ethoxycarbonyl.
Haloalkoxy is, for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy,
2,2,2-trifluoro-
ethoxy, 1,7,2,2-tetrafluoroethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2,2,2-
trichloroethoxy or
pentafluoroethoxy.
The cycloalkyl radicals suitable as substituents are, for example,
cyclopropyl, cyclobutyl,
cyciopentyl and cyclohexyl.
The halocycloalkyl radicals suitable as substituents are, for example, mono-,
di- or per-


CA 02291101 1999-11-24
WO 99/09023 - 7 - PCT/EP98/05247
halogenated cycloalkyl radicals, for example fluorocyclopropyl,
chlorocyclopropyl, bromo-
cyclopropyl, 2,2-dichlorocyclopropyl, 2,2-difluorocyclopropyl, 2,2-
dibromocyclopropyl, 2-
fluoro-2-chlorocyclopropyl, 2-chloro-2-bromocyclopropyl, 2,2,3,3-
tetrafluorocyclopropyl,
2,2,3,3-tetrachlorocyclopropyl, pentafluorocyclopropyl, fluorocyciobutyl,
chlorocyclobutyl,
2,2-difluorocyclobutyl, 2,2,3,3-tetrafluorocyclobutyl, 2,2,3-trifiuoro-3-
chlorocyclobutyl, 2,2-
dichloro-3,3-difluorocyclobutyl, fluorocyctopentyl, difluorocyciopentyl,
chlorocyclopentyl,
perfluorocyciopentyl, chlorocyclohexyl and pentachlorocyclohexyl.
Alkylthio is, for example, methylthio, ethylthio, propylthio or butylthio or a
branched isomer
thereof.
Phenyl per se, or as part of a substituent, such as, for example, phenylthio
or ben2oyloxy,
may be unsubstituted or substituted, in which case the substituents may be in
the ortho-,
meta- or para-position. Unless specifically indicated, substituents are, for
example, C,-C4-
alkyl, C,-C4alkoxy, halogen or C,-C4haloalkyl.
Corresponding meanings may also be given to the substituents in combined
definitions,
such as, for example, alkyl-S(O)-, alkyl-ON=CH-, (alkyl)2NC0-, alkenyl-SO-,
alkynyl-S{O)~2-,
alkylcarbonyloxy-, haloalkoxycarbonyl-, haloalkyl-S(O)20-, haloalkyl-SO-,
(alkyl)2NS(O}2-,
alkyl-S(O)20-, alkyl substituted by unsubstituted or R"-substituted phenyl,
alkenyl
substituted by unsubstituted or R"-substituted phenyl, alkyl-S(O)2NH-,
haloalkyl-S(O}2NH-,
aIkyINHS(O)2-, aIkyINHCO-, haloaIkyINHCO-, (alkyl)2NCS-, H(alkoxy)P(O)O-,
alkyl(alkoxy)P(O)O-, (alkoxy)2P(O)O-, alkoxycarbonyl-alkenyl, alkyl-S(O)~2
substituted by
unsubstituted or R"-substituted phenyl, alkoxy-alkyl-S(O)"2- and alkynyl-
S(O)"2-.
In the definitions of cyanoalkyl, alkylcarbonyl, alkoxycarbonylaikenyl,
alkylcarbonyloxy,
alkoxycarbonyl, alkoxycarbonyloxy and haloalkoxycarbonyl, the upper and lower
limits of
the number of carbon atoms given in each case do not include the cyano or
carbonyl
carbon atom, as the case may be.
The compounds of formula I wherein D is a group 4, to Q4 and Re is OH can be
in the form
of mixtures of the following isomeric forms I, to 14 and Ic:


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WO 99/09023 - 8 - PCT/EP98/05247
R, R~
RZ S(O)n O O RZ S(O)n OH O
R3 C _ R3 C w
Ra I ~ Z~~ ~ Ra I ~ Z.Zz\
Rs O , (CHz)na Rs O ' (C~)na
l2
~\ R R,
2 S(O)n O OH
R3 C
Ra I
O RS O , (CHZ)na
R R,
R x S(O)n O ~ ~ Is
3
c
Ra I ~ ~O Z,'w-(CHz)n
4
Rs Rz R,
S(O)n O O
!c Rs
Ra i ~ I Zi
RS HO , (CHZ)n
4
In the above isomeric compounds of formulae I, to 14 and Ic:
when Z, = C(R6)R,, Z2 = (W),~, Z3 = C(Rs)R, and n4 = 0, the right-hand portion
of the
isomeric compounds represents the group Q,;
when Z, = CH, Z2 = O, S or -(CH2)~5-, Z3 = CH and n4 = 2, the right-hand
portion of the
isomeric compounds represents the group Q2;
when Z, = CH2, Z2 = CHNHR9, Z3 = CHZ and n4 = 0, the right-hand portion of the
isomeric
compounds represents the group Q3; or
when Z, = NR,o, Z2 = O, Z3 = C(Rg)R, and n4 = 0, the right-hand portion of the
isomeric
compounds represents the group Q4.
The compounds of formula I wherein Q is a group QS may also be in the form of
mixtures of
the following isomeric forms Is, I, and le:


CA 02291101 1999-11-24
WO 99109023 PCT/EP98/05247
-9-
R~ R~
R Rz S~O)n 101 R" R Rz S~O)n ~H R"
Cr 3 C \
R4 !~ ( \\N ~ R4 I w \N
R / OH N R / O N~
R,z R,z
Ig I-
\'~ !/
R
Rz ~ O R"
R St0)n C \ ~ \
3 N
R4 ~ O N
i
R R~z
s
le
The invention includes all those isomeric forms I, to l4, Ic, I6, h and le and
their mixtures I, to
1, and lc, and Is, h and le.
The invention likewise includes the salts that the compounds of formula I
having azide
R,
Rz S(O)rt 0 OH
hydrogen, for example the compounds of formulae 13 and Is ~'R ~ I c ~ z~
R O Z,~~-~Z~(CHz)
n,
R,
Rz S(O)n O
OH
and R3 ~ c ,, (I6), and the derivatives having carboxylic acid and
R' I ~ ; '~-R,z
N
R$ R"
sulfonamide groups (e.g. carboxy-substituted phenyl, alkyl-S(O)2NH and
haloalkyl-S(O)2NH
groups) are able to form with bases. Those salts are, for example, alkali
metal salts, e.g.
sodium and potassium salts; alkaline earth metal salts, e.g, calcium and
magnesium salts;
ammonium salts, that is to say unsubstituted ammonium salts and mono- or poly-
substituted
ammonium salts, e.g. triethylammonium and methylammonium salts; or salts with
other
organic bases.
Among the alkali metal and alkaline earth metal hydroxides as salt formers,
attention is


CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
-10-
drawn, for example, to the hydroxides of lithium, sodium, potassium, magnesium
and
calcium, but especially to the hydroxides of sodium and potassium. Suitable
salt formers are
described, for example, in WO 97/411 t2.
Among the alkali metal and alkaline earth metal hydrides attention is drawn,
for example, to
sodium hydride and calcium hydride, and among the carbonates attention is
drawn to the
carbonates of sodium, potassium, caesium, calcium, barium, magnesium and
lithium.
Examples of amines suitable for ammonium salt formation include ammonia as
well as
primary, secondary and tertiary C,-C,ealkylamines, C,-Cahydroxyalkylamines and
C2-C4-
alkoxyalkylamines, for example methylamine, ethylamine, n-propylamine,
isopropylamine,
the four isomers of butylamine, n-amylamine, isoamylamine, hexylamine,
heptylamine,
octylamine, nonylamine, decylamine, pentadecylamine, hexadecylamine,
heptadecylamine,
octadecylamine, methylethylamine, methylisopropylamine, methylhexylamine,
methylnonyl-
amine, methylpentadecylamine, methyloctadecylamine, ethylbutylamine,
ethyfheptylamine,
ethyloctyiamine, hexylheptylamine, hexyloctylamine, dimethylamine,
diethylamine, di-n-
propylamine, diisopropylamine, di-n-butylamine, di-n-amylamine,
diisoamylamine,
dihexylamine, diheptylamine, dioctylamine, ethanolamine, n-propanolamine,
isopropanol-
amine, N,N-diethanolamine, N-ethylpropanolamine, N-butylethanoiamine,
allylamine,
n-butenyl-2-amine, n-pentenyl-2-amine, 2,3-dimethylbutenyl-2-amine, dibutenyl-
2-amine,
n-hexenyl-2-amine, propylenediamine, trimethylamine, triethyfamine, tri-n-
propylamine,
triisopropylamine, tri-n-butylamine, triisobutylamine, tri-sec-butylamine, tri-
n-amylamine,
methoxyethylamine and ethoxyethylamine; heterocyclic amines, for example
pyridine,
quinoline, isoquinoline, morpholine, thiomorpholine, piperidine, pyrrolidine,
indoline,
quinuclidine and azepine; primary aryfamines, for example anilines,
methoxyanilines,
ethoxyanilines, o-, m- and p-toluidines, phenylenediamines, benzidines,
naphthylamines
and o-, m- and p-chloroanilines; but especially triethylamine, isopropylamine
and
diisopropylamine.
The salts of compounds of formula I having basic groups, especially having
basic amino
groups, for example alkylamino and diafkylamino groups, in the definition of
Rs, R~ or R"
are, for example, salts with inorganic or organic acids, for example
hydrohaiic acids, such
as hydrofluoric acid, hydrochloric acid, hydrobromic acid or hydriodic acid,
and also sulfuric
acid, phosphoric acid, nitric acid, and organic acids, such as acetic acid,
trifluoroacetic acid,
trichloroacetic acid, propionic acid, glycolic acid, thiocyanic acid, citric
acid, benzoic acid,


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WO 99/09023 - 11 - PCT/EP98/05247
oxalic acid, formic acid, benzenesulfonic acid, p-toluenesulfonic acid and
methanesulfonic
acid.
The possibility of the presence of at feast one asymmetrical carbon atom in
the compounds
of formula I, for example in the substituent R,, where R, is a branched alkyl,
alkenyl, halo-
alkyl or alkoxyalkyl group, or where R, and R2 and/or R3 and R4, and Rs and R~
are different
from one another, means that the compounds may occur in the form of optically
active
single isomers or in the form of racemic mixtures.
Because rotation between the benzoyl and the Q, to Qs ring systems is
hindered, the com-
pounds of formula I may also be in the form of rotational isomers
(atropisomers).
In the present invention, "compounds of formula I" is to be understood as
including both the
pure optical antipodes and the racemates or diastereoisomers and atropisomers.
When an aliphatic C=C or C=N-O double bond (synlanti) is present, geometric
isomerism
may occur. The present invention relates to those isomers also.
Preference is given to compounds of formula I wherein R, is C,-C4alkyl, C,-
C4haloalkyl,
C,-Caalkoxy-C,-C4alkyl, C,-C4alkoxycarbonyl, cyano, cyano-C,-C4alkyl, CHO, C,-
Caalkyl-
ON=CH, C2-Csalkenyl, C,-Caalkoxycarbonyl-C2-Csalkenyl or a group -CH(OR2o)OR2,
;
W is oxygen, sulfur, -C(R,e)2- or -N(Rz2)-; each R,e independently of the
other is hydrogen,
C,-Caalkyl or C,-Caalkoxycarbonyl; and R22 is hydrogen, C,-C4alkyl or C,-
C4alkoxycarbonyl.
Re
Also preferred are compounds of formula I wherein Q is a group ~ (Q2),
Y
O
R8 ~ R" R
13
(Qs) or \N (Qs); R6 and Rare each
/ ~~R~ (Qa)~ OH r N\N
O N ~ R~4 O
R,2
independently of the other C,-C4alkyl or C,-C4alkyl-S(O)~2; n2 is 0; RB is OH,
C,-C4alkoxy,
C,-C4alkylcarbonyloxy, phenylthio or C,-C4alkylthio; R,o, R" and R,2 are each
independently


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WO 99/09023 - 12 - PCTIEP98105247
of the others hydrogen, C,-C4alkyl or C,-C4alkoxycarbonyl; R,3 is halogen, C,-
Caalkyl, C3-Cs-
cycloalkyl, COOR,s, COR,S or cyano; R,a is C,-C4alkyl, C3-Csalkynyl, C3-
Cscycloalkyl or
C3-Cscycloalkyl substituted by halogen, C,-C4alkyl, C,-C4haloalkyl, C3-
CBalkenyl, C3-Cshalo-
alkenyl, C3-Csalkynyl, C3-Cshaloalkynyl or phenyl; R,5 is C,-C4alkyl, C,-
C4haloalkyl, C3-Cs-
alkenyi, C3-Cshaloalkenyl, C3-Cealkynyl, C3-Cshaloalkynyl or phenyl; and R,s
and Y are as
defined for formula I.
O
Rs
Also preferred are compounds of formula I wherein D is a group ~ ( ~~ ~ (Q,)
or
Rs X ns
Rs R~
O
(Q3); Rs and R~ are each independently of the other C,-C4alkyl or
R9
R8 NH
C,-C4alkyl-S(O)n2~ na is 0; Rs is OH, C,-C4alkoxy, C,-C4alkyicarbonyloxy,
phenylthio or
C,-C4alkylthio; W is oxygen or -C(R,e)2 ; R18 IS hydrogen; ns is 1; and R9 is
(C,-C4alkyl)-
NHCO or (C,-C4alkyl)ZNCO.
Preference is given also to compounds of formula I wherein n is 1 or 2.
The process according to the invention for the preparation of compounds of
formula I
R~
R2 S(O)~ O
R3 ~ C~Q (I)
Rs
O
Rs
wherein R, to R5 and n are as defined for formula I; Q is a group ~ (W R~
(Q,),
Rs X ns
Rs R~


CA 02291101 1999-11-24
WO 99109023 . 13 _ PCT/EP98/05247
Re
Rs O Rs
{Qz), I (Q3) or / ~ R, {Qa); Ra is OH; and R6,
O Re NH~Rg O N
Rio
R,, R9, R,p, W, nfi and Y are as defined for formula I is carried out
analogously to known
procedures and comprises either
a) reacting a compound of formula III
R~
RZ S(O)n O
Rs , C~X (III),
R4
R5
wherein R, to R5 and n are as defined and X is a leaving group, e.g, halogen,
in an inert
organic solvent in the presence of a base with a compound of formula IV
O
(IV),
HO Z~ Z ~ (CH2)
n4
wherein
Z, is C(Rs)R,, Zz is {W)~s, Z3 is C(Rs)R~ and n4 is 0 (= group Q,);
Z, is CH, Zz is oxygen, sulfur or -(CHz)"5- (=Y), Z3 is CH and n4 is 2 (=
group Qz);
Z, is CHz, Z2 is CHNHRe, Z3 is CHz and n4 is 0 (= group Q3); or
Z, is NR,o, Z2 is oxygen, Z3 is C(Rs)R, and n4 is 0 (= group Q4).
and Rs, R,, R9, Rya, W, nB and n5 are as defined for formula I, to form a
compound of
formula lc
R, O
R2 S(O)n O Z3
ii
C,O Z~Z2~ (Ic).
Ra ~ ' ~\ (CH2)~,
Rs


CA 02291101 1999-11-24
WO 99/09023 - 14 _ PCTIEP98/05247
and then isomerising that compound, for example in the presence of a base and
a catalytic
amount of a cyanide source; or
b) reacting a compound of formula Id
R,
O
R3 n
R i C~OH (Id)~
4
Rs
wherein R, to R5 and n are as defined, with a compound of formula IV
O
(IV),
HO Z 2
' ~ (CH2)
wherein Z,, Z2, Z3 and n4 are as defined, in an inert organic solvent in the
presence of a
base and a coupling agent to form a compound of formula Ic
R~ O
R2 S(O)
O
Ra / C~O Z'''w(CH )
2 nn
Rs
and then isomerising that compound, for example as described under Route a).
The process according to the invention for the preparation of compounds of
formula I
Rt
S(O)~ O
C~(~ (I)
R4
Rs


CA 02291101 1999-11-24
WO 99109023 PCTIEP98/05247
_ ~c~ _
R~~
wherein R, to R5 and n are as defined for formula I; Q is a group ~ \N (Q5);
and
OH N
i
R,z
R" and R,2 are as defined for formula I is carried out analogously to known
procedures and
comprises either:
a) reacting a compound of formula III
R1
R2 S~O~n
Rs , C'X (III),
R4
Rs
wherein R, to R5 and n are as defined and X is a leaving group, e.g. halogen,
with a
compound of formula IVa
t,z
HO N'N (IVa),
\ I
R"
wherein R" and R,2 are as defined, in an inert organic solvent in the presence
of a base to
form a compound of formula le
Ri R,z
S(O)
R3 n O N'N
R4 , I C,~O ~ ~ (ie)~
R, ~
R5
and then isomerising that compound, for example in the presence of a base and
a catalytic
amount of a cyanide source; or
b) reacting a compound of formula Id


CA 02291101 1999-11-24
WO 99/09023 PCT/EP98I05247
-16-
R,
R2 S(O)n
O
R3 11
R , I C_OH (Id).
4
R5
wherein R, to R5 and n are as defined, with a compound of formula IVa
~12
HO ~ 'iN (IVa),
R"
wherein R" and R,2 are as defined, in an inert organic solvent in the presence
of a base
and a coupling agent to form a compound of formula le
R
R2 S(O~
n O hl w
(le),
4
\ R"
R5
and then isomerising that compound as described under Route a).
The process according to the invention for the preparation of compounds of
formula I
R,
R2 S(O)~ O
R3 ~ ~~Q (I)
R4
R5
Ris
wherein R, to R5 and n are as defined for formula 1; D is a group j \\N (Q6);
R,3 is
R,4 O
hydrogen, C,-C4alkyl, C,-Caalkyl substituted by unsubstituted or R"-
substituted phenyl,
C,-Cahaloalkyl, C2-C$alkenyl, C2-Csalkenyl substituted by unsubstituted or R"-
substituted
phenyl, C2-Cgalkynyl, C2-Csalkynyl substituted by unsubstituted or R,~-
substituted phenyl,


CA 02291101 1999-11-24
WO 99/09023 PCT/EP98105247
_j7_
C3-Cshaloalkenyl, C3-Cehaloalkynyl, C3-CBcycloalkyl, C3-Cscycloalkyl
substituted by halogen,
R,5 or COOR,s; C,-C4alkyl-S(O)~z, C,-Cealkyl-S(O)"2substituted by
unsubstituted or R,~-
substituted phenyl, C,-C4alkoxy-C2-CBalkyl-S(O)~2, C2-Cealkenyl-S(O)~2, C2-
Csalkenyl-S(O)"2
substituted by unsubstituted or R,~-substituted phenyl, C2-Cealkynyl-S{O)~2 or
CZ-Csalkynyl-
S(O}~2 substituted by unsubstituted or R,~-substituted phenyl; and R,4 to R,~
and n2 are as
defined for formula I, is carried out analogously to known procedures and
comprises either:
a) converting a compound of formula V
R~
Rz S(O)
R3 _ ~ O O
-C~
R4 ~ ~ CHZ R~4
w
R5
wherein R, to R5, R,4 and n are as defined, in the presence of a base, carbon
disulfide and
an alkylating reagent of formula VI
R25-Xv (VI),
wherein R25 is C,-C4alkyl, C,-C4aikyl substituted by unsubstituted or R"-
substituted phenyl,
C,-C4alkoxy-C2-Csalkyl, C2-Csalkenyl, C2-Csalkenyl substituted by
unsubstituted or R,~-
substituted phenyl, C2-Csalkynyl or C2-Csalkynyl substituted by unsubstituted
or R"-
substituted phenyl; R,7 is as defined for formula I, and X, is a leaving
group, e.g. halogen or
sulfonate, into a compound of formula VII
R~
R2 S(O)
R3 ~ O O
R ~ C, il ~C,R14 (VII).
4
C
R5 SR \ SR
25 25
wherein R, to R5, R,4, R25 and n are as defined, then cyclising that compound
with hydroxyl-
amine hydrochloride, optionally in a solvent, in the presence of a base to
form a compound
of formula If


CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
_18_
R,
R2
S(O)~ O R~s
R3 I I
C v (If},
Ra \ I , O
R5 R,a
wherein R, to R5, R,a and n are as defined, R,3 is R25S and R25 is C,-Caalkyl,
C,-Caalkyl
substituted by unsubstituted or R»-substituted phenyl, C,-Caalkoxy-Cz-Csalkyl,
C2-Csaikenyl,
C2-Cfialkenyl substituted by unsubstituted or R"-substituted phenyl, C2-
Csalkynyl or C2-C6-
alkynyl substituted by unsubstituted or R»-substituted phenyl, and then
oxidising that com-
pound, for example with meta-chloroperbenzoic acid (m-CPBA); or
b) converting a compound of formula V
R~
R2
S(O) ~ O O
R3 II 11
R ~ C~.CH2 C"R,a (V).
4
R5
wherein R, to R5, R,a and n are as defined, with an orthoacid amide of formula
VIII
R260~~-N(R2,)2 (VIII),
zs R,s
wherein R,3 is hydrogen, C,-Caalkyl, C,-Caalkyl substituted by unsubstituted
or R"-
substituted phenyl, C,-Cahaloalkyl, C2-Csalkenyl, C2-Cealkenyl substituted by
unsubstituted
or R,~-substituted phenyl, C2-Csalkynyl, C2-Csalkynyl substituted by
unsubstituted or R,~-
substituted phenyl, C3-Cshaloalkenyl, C3-CBhaloalkynyl, C3-Cscycloalkyl or C3-
Cscycloalkyl
substituted by halogen, R,5 or COOR,s; R,5 to R" are as defined for formula I;
and R26 and
R2, are each independently of the other C,-Caalkyl, into a compound of formula
IX
R~
S(O~~ O O
R3 II II
R , C~iI~C~R~a (IX),
4
\
R R 3 \N(R2~)2
*rB


CA 02291101 1999-11-24
WO 99/09023 - 1 g _ PCT/EP98/05247
wherein R, to R5, R,3, R,A, n and R2~ are as defined, and then cyclising that
compound in
the presence of hydroxylamine hydrochloride, optionally in a solvent, in the
presence of a
base to form a compound of formula If
R~
R2
S(~)~ O R~s
R3 I I
C v (If).
Ra
RS R~4
The process according to the invention for the preparation of compounds of
formula Id
R~
S(O)S O
(Id)
i C~OH
R5
wherein R,, R3 to RS and n are as defined for formula I and R2 is CH3 is
carried out
analogously to known procedures and comprises either:
a} etherifying a compound of formula XX
OH O
II
i I ~ ~ OR28 (XX),
Rs
wherein R5 is as defined for formula I and R2g is C,-C4alkyl, with a compound
of
formula XXV
Rs' R,
~C=C~HZ Hal (XXV),
Ra
wherein R,, R3 and R4 are as defined for formula 1 and Hal is halogen, to form
a compound
of formula XXI


CA 02291101 1999-11-24
WO 99109023 PCTIEP98I05247
-20-
R3
CH '
O O
R~ II
C ~ OR2a (XXI)
Rs
wherein R1, R3 to Rs and R2g are as defined, subjecting that compound to a
Claisen
rearrangement and then acylating the resulting compound of formula XXII
H2C R~
OH O
11
Rs , C.
OR2a (XXII)
Rs
with a compound of formula XXVI
S
Hal-C-N(C~-C4alkyl)2 (XXVI),
wherein Ha! is chlorine, bromine or iodine, to yield a compound of formula
XXIII
N\ ~-C4alkyl)2
C=S
H2C R,
O O
il
R3 i I C~OR28 (XXIII),
Ra
Rs
which is subjected to a rearrangement and yields a compound of formula XXIV
N(C1-C481ky1)2
H2C R~
S O
II (XXIV),
R3 i C~OR
R
4
R5
then hydrolysing and cyclising that compound to form a compound of formula Id


CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
-21 -
R~
RZ S(O)n O
Ra / C~OH (Id).
R<
Rs
wherein R, and R3 to RS are as defined, R2 is CH3 and n is 0, and then
oxidising that
compound (n is 1 or 2); or
b) first brominating a compound of formula XX
OH O
II
/ ' C~OR28 (XX),
R5
wherein RS and Rze are as defined, to yield a compound of formula XXb
OH O
II
Br / C~OR (XXb),
~e
Rs
subjecting that compound to a coupling reaction in the presence of a catalyst
and an
organometal reagent of formula XXVb
R~ R3
CH2=C-C-Sn(RZ9)3 (XXVb),
R4
wherein R,, R3 and R4 are as defined and R29 is C,-G4alkyl, to yield a
compound of
formula XXII
O
11
(XXII),
2B
R5
H2C R~
OH
wherein R,, R3 to R$ and R~ are as defined, and reacting that compound further
analogously to the method described under Route a) to form a compound of
formula Id.


CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
-22-
The process according to the invention for the preparation of compounds of
formula Id
R~
R2 S(O)n O
R3 , C~OH (Id)
R4
Rs
wherein R,, R3 to Rs and n are as defined for formula I and R2 is CH3 is
carried out
analogously to known procedures and comprises reacting a compound of formula
XXa
Br O
t
~ C~OR28 (XXa),
w
Rs
wherein Rs is as defined and R28 is C,-Caalkyl, with a compound of formula
XXVa
Rs'
~C=C-CHz SH (XXVa),
RQ
wherein R,, R3 and R4 are as defined, to yield a compound of formula XXIa
Ra
CH \
S O
R tt
i
C ~OR2e (XXIa),
Rs
subjecting that compound to a Claisen rearrangment to yield a compound of
formula XXlla
H2C R1
SH O
tl
R3 i I C~OR28 (XXlla),
Ra
R5
which is then hydrolysed and cyclised to form a compound of formula Id


CA 02291101 1999-11-24
WO 99/09023 - 23 - PCT/EP98/05247
R,
Rz S(O)n O
C~OH
Ra
Rs
wherein R, and R3 to Rs are as defined, R2 is CH3 and n is 0, and then
oxidising that
compound (n is 1 or 2).
The process according to the invention for the preparation of compounds of
formula I
R~
R2 S(O)n O
R3
Ra
Rs
wherein R, to Rs and n are as defined for formula I and Q is halogen is
carried out
analogously to known procedures and comprises treating a compound of formula
Id
R,
R2 S(O)n O
~~OH (Id).
Ra
Rs
wherein R, to Rs and n are as defined, with a halogenating agent.
The preparation of the compounds of formula I is illustrated in more detail in
the following
Reaction Schemes 1 to 6.
*rB


CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
-24-
Reaction Scheme 1
Route a):
R~
R2
S(O)n O O
R3 C
R4 ~ I ~X ~ ~ base e.g. (C2H5)3N,
+ Z~zz~ solvent e.g. CH3CN,
R5 HO ; (CH2)n4 0_110°C
III IV
O ~ R,
R~ S(O)n ~ O
S(O) O ~ isomerisation: Ra C
R n C ( /~~ base e.g. (C2H5)3N, R4 %~ I ~Z3
3
R i ~O Z,'----(CH2) KCNcat.
a \ I na R5 Re Z, --..._ (CH2)n
4
R5
lc I (RB - OH)
Route b):
R R,
S(O)S O O
R3 C
R i ~OH ~ base e.g. (C2H5)3N, coupling
+ ~ ~~\ reagent e.g.
RS HO z, "-- (CH2)n I
Id IV 4 I- N~C1
I
CH3
solvent e.g. CH3CN,
0-110°C
O R R~
z
R2 R' isomerisation: R3 S(O)n ~ O
S(O)n O ~ base e.g. (C2H5)3N,
R3 C~ I ~Zz~ KCN R4 / I I Zs
I O Z~ ~ (CH2) n cat. ~ R
Z,'.----(CH2)
R na
Ic I (R8 = OH)


CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
-25-
In Reaction Scheme 1
when Z, = C(R6)R~, Z2 = (W)~g, Z3 = C(Rs)R, and n4 = 0, the right-hand portion
of the
compounds of formula I represents the group Q,;
when Z, = CH, Z2 = O, S or -(CH2)~5-, Z3 = CH and n4 = 2, the right-hand
portion of the
compounds of formula I represents the group Q2;
when Z, = CHz, Z2 = CHNHR9, Z3 = CH2 and n4 = 0, the right-hand portion of the
compounds
of formula I represents the group Q3; or
when Z, = NR,o, Z2 = O, Z3 = C(Rs)R, and n4 = 0, the right-hand portion of the
compounds
of formula I represents the group Q4.
Reaction Scheme 2
Route a):
R
R z
g(p)~ p ',2
R3
C~X HO N~N
R4 %~ + \ / base e.g. (C2H5)3N,
solvent e.g. CH3CN,
Rs R" 0-110°C
IVa
R R,
2 O
R2 R~ R\N_ isomerisation: R3 S(O) n C R»
R S(O)n ~ N base e.g. (C2H5)3N, i
R ~ C\'O ~ , KCN R4 ~ I ~ ~N
t R~~ cat. HO N
w Rs I
R5 R,2
le I (Q=QS)


CA 02291101 1999-11-24
WO 99/09023 PCTIEP98/05247
-26-
Route b):
R~
R2
S(O)S O
R3 ~ C~OH HO \N iN base e.g. (C2H5)3N, coupling
R4
+ ~--~ reagent e.g.
R5 R»
Id IVa I- NCI
I
CH3
solvent, e.g. CH3CN,
0-110°C
R,
RZ R' ( ) R~2 isomerisation: RZ S(O)n ~ R~~
R S O n ~ N ~ base e.g. (C2H5)3N, ~ Ra
' Coo \ IN KCNcat. R' ' ~ 4 NN
w R" RS v HO v
R5 R~2
le I (Q=QS)


CA 02291101 1999-11-24
WO 99109023 PCTIEP98/05247
-27-
Reaction Scheme 3
Route a):
R, R,
Rz S(O) O O K CO lCS , R -X , Rz S(O) O O
n n z a z xs , n II
VI R C
'R i I C~CH2C~R,4 solvente.g.DMF,or 3R4 ~ ~ C~~~ ~R,4
' ~ KFIAI/CSz, Rzs-X~ w C
R VI Rs RzsS~ SRzs
s solvent e.g. CH3CN, or
NaHICSz, Rzs X,,
V VI
solvent e.g. DMSO VII
R~
Rz S(O)S ii R,s
NHzOH ~ HCI, base e.g. R3 ~ C I ~ IOj e,g. m-CPBA
NaOAc/CzH50H R4 \ ~ N
O
Rs R,4
It (R~3=RzsS-)
R~
Rz S(O)n ~ R,s
R3R ~ ~ C ~ ~N
4
p
Rs R,a
If (R~3=RzsSO- or RzsSOz-)
Route b):
R, R2s0 R,
S(O) O O R O~C N(R27)2 R2 S(O) O O
n II a 2s R n II
R3 C' ~C~ ,3 R3
R4 \ I CH2 R" VIII R4 ~ I C R,4
C, '
R5 R5 R13 N(R27)2
V
IX
R~
R2 S(O)n ~ Rt3
NH20H ~ HCI, base e.g. R3 ~ C
Na0AGC2H50H R4 ~ ~ ~ O N
R5 R14
If


CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
- 28 _
For the preparation of compounds of formula I wherein 4 is a group Q, to Qa
and R8 is OH,
according to Reaction Scheme 1, Route a), the starting materials used are
carboxylic acid
derivatives of formula III wherein X is a leaving group, e.g. halogen, for
example iodine,
bromine or especially chlorine, N-oxyphthalimide or N,O-dimethylhydroxylamino
or part of
an activated ester, e.g. ' rN=C-NH-( ) (formed from dicyclohexylcarbodiimide
o ~J-
C H N=C-NH(CH ) N(CH )2
(DCC) and the corresponding carboxylic acid) or 2 5 0- 2 3 ' (formed from
N-ethyl-N'-(3-dimethylaminopropyl)-carbodiimide {EDC) and the corresponding
carboxylic
acid). Those starting materials are reacted in an inert organic solvent, for
example a
halogenated hydrocarbon, e.g. dichloromethane, a nitrite, e.g. acetonitrile,
or an aromatic
hydrocarbon, e.g. toluene, and in the presence of a base, for example an
alkylamine, e.g.
triethyfamine, an aromatic amine, e.g. pyridine or 4-dimethyiaminopyridine
(DMAP), with a
dione derivative of formula IV to form isomeric snot ethers of formula Ic. The
esterification
takes place at temperatures of from 0°C to 110°C.
The isomerisation of the ester derivatives of formula Ic to form the dione
derivatives of
formula I (Re = OH) can be carried out, for example, analogously to EP-A-0 369
803 in the
presence of a base, for example an alkylamine, e.g. triethylamine, or a
carbonate, e.g.
potassium carbonate, and a catalytic amount of a cyanide source, for example
acetone
cyanohydrin or potassium cyanide.
According to Reaction Scheme 1, Route b), the desired diones of formula I (RB
= OH) can
be obtained, for example, analogously to Chem. Lett. 1975, 1045 by
esterification of the
carboxylic acids of formula Id with the dione derivatives of formula IV in an
inert solvent, for
example a halogenated hydrocarbon, e.g. dichloromethane, a nitrite, e.g.
acetonitrile, or an
aromatic hydrocarbon, e.g. toluene, in the presence of a base, for example an
afkylamine,
e.g. triethylamine, and a coupling agent, for example 2-chforo-1-methyl-
pyridinium iodide.
The esterification is carried out, depending upon the solvent used, at
temperatures of from
0°C to 110°C and yields first, as described under Route a), the
isomeric ester of formula Ic,
which can be isomerised as described under Route a), for example in the
presence of a
base and a catalytic amount of a cyanide source, to form the desired dione
derivative of
formula I (Re = OH).


CA 02291101 1999-11-24
WO 99/09023 - 29 - PCT/EP98/05247
According to Reaction Scheme 2, the compounds of formula I wherein Q is a
group QS can
be obtained in a manner analogous to that described, for example, in Reaction
Scheme 1 or
Tetrahedron 36, 2409 (1976), either
a) by esterification of a carboxylic acid derivative of formula III with the
hydroxypyrazole
derivative of formula IVa in an inert organic solvent and in the presence of a
base, or
b) by esterification of the carboxylic acid of formula Id with the
hydroxypyrazole derivative of
formula IVa in an inert solvent in the presence of a base and a coupling
agent, and subse-
quent isomerisation of the intermediately formed ester of formula le, for
example with the
aid of a base and a catalytic amount of cyanide source.
The preparation of the compounds of formula I wherein Q is the group Q6 can be
carried out
in accordance with Reaction Scheme 3 advantageously either
via Route a) by reacting the ~3-diketone derivative of formula V, e.g.
analogously to
Synthesis 1991, 301; ibid. 1988, 793; or Tetrahedron 32, 3055 (i 976), with
carbon disulfide
in the presence of a base, for example a carbonate, e.g. potassium carbonate,
a metal
hydride, e.g. sodium hydride, or potassium fluoride on aluminium, and an
alkylating reagent
of formula VI wherein X, is a leaving group, e.g. halogen, for example iodine,
bromine or
especially chlorine, R250S0z0-, CH3S020- or ~H3 ~ ~ 5020- . The reaction is
advantageously carried out in a solvent, for example an amide, e.g. N,N-
dimethylformamide
(DMF), a sulfoxide, e.g. dimethyl sulfoxide (DMSO), or a nitrite, e.g.
acetonitrile. The
resulting ketene thioacetal of formula VII is cyclised with the aid of
hydroxylamine
hydrochloride in the presence of a base, for example sodium acetate, in a
solvent, for
example an alcohol, e.g. ethanol, or an ether, for example tetrahydrofuran, to
form a
compound of formula if wherein R,3 is R25S-. The cyclisation reaction is
advantageously
carried out at temperatures of from 0°C to 100°C. If desired,
the compound of formula If can
be oxidised analogously to known standard procedures, e.g. with peracids, for
example
meta-chloroperbenzoic acid (m-CPBA) or peracetic acid, to form the
corresponding sulfone
or sulfoxide of formula If (R,3 = R25S0- or R25S02-); or can be carried out
via Route b), by converting the ~-diketone derivative of formula V analogously
to J. Het.
Chem. 20, 645 (1983) with an orthoacid amide of formula Vlli, for example


CA 02291101 1999-11-24
WO 99/09023 - 30 - PCT/EP98/05247
dimethylformamide dimethyi acetal, into the enamine derivative of formula IX
and then
cyclising that derivative with the aid of hydroxylamine hydrochloride, in the
presence of a
base, e.g. sodium acetate, in a solvent, for example an alcohol, e.g. ethanol,
to form a
compound of formula If.
The preparation of the 4-benzoylisoxazole derivatives of formula I (Q=Qs)
wherein R13 is
COOR,6, COR,S, cyano, nitro or CONH2 can also be carried out, for example,
analogously
to WO 96121357 and references cited therein.
The carboxylic acids of formula id can be prepared analogously to known
procedures, e.g.
in accordance with the methods given in Reaction Schemes 4 and 5 below.


CA 02291101 1999-11-24
WO 99/09023 - 3~ - PCTIEP98/05247
Reaction Scheme 4
Route a)
OH O R C~C~CH;O O
C ~ R° R I I
ORza alkenylation: ' ~ C.
ORzB
R, I
Rs XX R,C=C-CH2 Hal Rs XXI
XXV
N\C~-C°alkyl)z
R~ R~ C=S
HzC OH O HzC O O
II II
Claisen rearrangement R3 C ~ acylation e.g. R C
R I ~ ORzs --~ s R ~ ~ ~ORze --r
T ° ~S 4
R ~ Hal-C ~ R
s ~N(C,-C°alkyl)z s
XXI I ~VI XXIII
N;C~-C°alkyl)z
R, C=O R
rearrangement H2 R3 S O. 1 ) hydrolysis R Rz S(O)n O
w ORze C
T, solvent R° I , 2) cyclisation R° I ~ ~OH
R5 i
XXIV Rs
Id (Rz=CH3; n-_ 0)
R R,
R z S(O)n O
(O) e.g. ~ C~OH
m-CPBA ~ R°
i
solvent, R
0-i i t7°C s
Id (Rz=CH3; n-_ 1 or 2 )


CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
-32-
Route b):
OH O OH O
C~ Br
OR28 bromination: Br2 ~ I ~ C~OR2a ~
i Lewis acid, solvent,
Rs 0-7 00°C Rs
XX XXb
R
H2C ' OH O
coupling II
Ra C. --r
ze
CHz=C~ C3 Sn(Rzs)a ~ Pd[(C6Hs)3PJ4 R4 I % OR ~ Id
R4 Rs
XXVb
XXI I
solvent, 0-200°C
Reaction Scheme 5
R3
Br ~ R4~~g O
C, aromat. nucleophifi Ic
i I OR2s substitution e.g. R~ , C~OR
\ 28
Rs R3 R, \
XXa R~C=C-CH2SH, solvent, Rs
XXVa XXIa
base, 0-200°C
R,
H2C R, SH R
R 2 S(O)S O
Claisen rearrangement R3 ~ C~ 3 C.
R /~~ OR2e 1 ) hydrolysis R4 ~ ( OH
T 4
Rs \ 2) cyclisation R w --i
XXlla Id (Rz=CH3; n=0)
R~
R2 S(O)n O
R3
[O) e.g. R
C~OH
m-CPBA~' \
R5
Id (R2=CH3; n=1 or2 )


CA 02291101 1999-11-24
WO 99/09023 - 33 - PCT/EP98/05247
The alkenylation of the salicylic acid derivative of formula XX wherein R28 is
C,-C4alkyl in
accordance with Route a) in Reaction Scheme 4 is carried out, for example,
analogously to
standard etherification methods by means of reaction with an allyl halide of
formula XXV
wherein Hal is halogen, especially chlorine, bromine or iodine, in an aprotic
solvent, for
example an amide, e.g. N,N-dimethylformamide (DMF) or 1-methyl-2-pyrrolidone
(NMP), a
sulfoxide, e.g. dimethyl sulfoxide (DMSO), a ketone, e.g. acetone, or a
nitrite, e.g. aceto-
nitrile, in the presence of a base, for example a carbonate, e.g. potassium or
caesium
carbonate, or a metal hydride, e.g. sodium hydride. The reaction temperatures
are
generally in the range of from 0°C to 110°C.
The subsequent Claisen rearrangement of the allyl ether of formula XXI in
Reaction
Scheme 4 can be carried out, for example, thermally at temperatures of from
100°C to
300°C, optionally in an inert solvent, for example an aromatic
hydrocarbon, e.g. xylene.
Alternatively the thermal Claisen rearrangement can be carried out, for
example, also
without a solvent in a microwave oven. Such Claisen rearrangements are
described, for
example, in C. Ferri, "Reaktionen der organischen Synthese", Georg Thieme
Verlag,
Stuttgart, 1978, page 461 ff..
In accordance with Reaction Scheme 4, the resulting phenol derivative of
formula XXIi is
then acylated, for example with a thiocarbamoyl halide of formula XXVI, e.g.
N,N-dimethyl-
thioformyl chloride, in an aprotic solvent, for example an amide, e.g. N,N-
dimethylformamide
(DMF) or 1-methyl-2-pyrrolidone (NMP), a sulfoxide, e.g. dimethyl sulfoxide
(DMSO), a
ketone, e.g. acetone, or a nitrite, e.g, acetonitrile, in the presence of a
base, for example a
carbonate, e.g. potassium or caesium carbonate, or a metal hydride, e.g.
sodium hydride.
The acylation is advantageously carried out at temperatures of from 0°C
to 110°C.
The rearrangement of the thiocarbamate of formula XXIII in Reaction Scheme 4
is effected,
for example, thermally in an inert solvent, for example an ether, e.g.
Biphenyl ether, at
temperatures of from 100°C to 300°C and yields the
thioicarbamate of formula XXIV. That
compound is then hydrolysed and cyclised using base or acid catalysis to form
a compound
of formula Id wherein R2 = CH3 and n = 0. This is effected advantageously
either with a
metal hydroxide, e.g. sodium hydroxide, or with a mineral acid, e.g.
hydrochloric acid or
sulfuric acid, at temperatures of from 0°C to 110°C. Suitable
solvents are, for example,
water, ethers, e.g. tetrahydrofuran, halogenated hydrocarbons, e.g.
dichloromethane, and
aromatic hydrocarbons, e.g. toluene.


CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
-34-
The resulting benzothiophene derivative of formula Id wherein R2 is methyl and
n is 0 can
then be oxidised in accordance with various standard methods. Advantageously
the
oxidation is carried out, for example, with hydrogen peroxide in an acidic
solvent, for
example an organic acid, e.g. acetic acid, or with an organic peracid, for
example meta-
chloroperbenzoic acid (m-CPBA), in an inert solvent, for example a halogenated
hydro-
carbon, e.g. dichloromethane, or an aromatic hydrocarbon, e.g. toluene. The
reaction
temperatures for the oxidation are generally in the range of from 0°C
to 110°C. The degree
of oxidation at the sulfur atom (n = 1 or 2) can be controlled by the amount
of oxidising
agent.
The above reaction sequence via acylation of the phenol derivative of formula
XXII to form
a thiocarbamate of formula XXlll, rearrangement of the latter compound to form
a thiol-
carbamate of formula XXIV and hydrolysis and cyclisation to form a compound of
formula Id
(n = 0) is carried out, for example, analogously to Org. Synth. 51, 139 (1971
}, and the
oxidation to form a compound of formula Id (n = 1 or 2) is carried out, for
example, as
described in H. O. House, "Modem Synthetic Reactions" W. A. Benjamin, Inc.,
Menlo Park,
California, 1972, pages 334-335 and 353-354.
The electrophilic bromination according to Route b} in Reaction Scheme 4 is
carried out, for
example, analogously to Chem. Communic. 1972, 214. The bromination of the
salicylic acid
derivative of formula XX can be effected, for example, in an inert solvent,
for example a
halogenated hydrocarbon, e.g. dichioromethane, and in the presence of a Lewis
acid, for
example titanium halide, e.g. titanium tetrachloride, at temperatures of from
0°C to 100°C.
The subsequent coupling of the resulting bromosalicylic acid derivative of
formula XXb to a
trialkyltin-olefin of formula XXVb wherein R29 is C,-C4alkyl is carried out
analogously to
Angew. Chem. 98, 504 (1986) in an organic solvent, for example an ether, e.g.
tetrahydro-
furan, an aromatic hydrocarbon, e.g. toluene, and in the presence a palladium
catalyst, for
example tetrakis(triphenylphosphine)paliadium. The reaction temperature is
advantageously
from 0°C to 200°C. The coupling product of formula XXII obtained
by Route b) can then, for
example in a manner analogous to that described under Route a), be acylated,
rearranged,
hydrolysed and cyclised, and optionally oxidised to form a compound of formula
Id.
The aromatic nucleophilic substitution of the ortho-bromobenzoic acid ester of
formula XXa
wherein R28 is C,-C4alkyl in Reaction Scheme 5 can be carried out analogously
to known
procedures, as described, for example, in J. March, "Advanced Organic
Chemistry", 4th


CA 02291101 1999-11-24
WO 99109023 - 35 - PCT/EP98I05247
Edition, John Wiley & Sons, New York, 1992, pages 641-876. Accordingly, the
benzoic
acid ester of formula XXa is reacted with an alkenyl sulfide of formula XXVa
in an aprotic
solvent, for example an amide, e.g. N,N-dimethylformamide (DMF) or 1-methyl-2-
pyrrolidone (NMP), a sulfoxide, e.g. dimethyl sulfoxide (DMSO), a ketone, e.g.
acetone, or a
nitrite, e.g. acetonitrile, in the presence of a base, for example a
carbonate, e.g. potassium
or caesium carbonate, or a metal hydride, e.g. sodium hydride, at temperatures
of from 0°C
to 200°C.
The subsequent Claisen rearrangement of the resulting thioallyl ether of
formula XXIa in
Reaction Scheme 5 can advantageously be carried out in a manner analogous to
that
described in J. Org. Chem. USSR 13, 2437 {1977) and under Reaction Scheme 4
for the
allyl ether of formula XXI, at temperatures of from 100°C to
300°C. The subsequent hydro-
lysis and cyclisation of the thiophenol of formula XXlla and the optional
oxidation of the
resulting dihydrobenzo[b]thiophene derivative of formula Id (n=0) are
advantageously like-
wise carried out as already described under Reaction Scheme 4.
The activated carboxylic acid derivatives of formulae III and I in Reaction
Schemes 1 and 2
{Route a)) wherein X is a leaving group, for example halogen, e.g. bromine,
iodine or espe-
cially chlorine, can be prepared according to known standard procedures as
described, for
example, by C. Ferri in "Reaktionen der organischen Synthese", Georg Thieme
Verlag,
Stuttgart, 1978, page 461 ff., such as, for example, in accordance with
Reaction Scheme 6
below.
Reaction Scheme 6
S(O?n O R2 S(OIn O
C~OH W~-X, DMF~t. , R3 C.
w ~ X Ra !~~ X
R 20-150°C
R
5
Id
III or I
In accordance with Reaction Scheme 6, the preparation of the compounds of
formula III
{X = leaving group) and I (X = halogen) is carried out, for example,
advantageously by the
use of a halogenating agent, for example a thionyl halide, e.g. thionyl
chloride or bromide; a
phosphorus halide or phosphorus oxyhalide, e.g. phosphorus pentachloride or
phosphorus


CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
-3s-
oxychloride, or phosphorus pentabromide or phosphoryl bromide; or an oxalyl
halide, e.g.
oxalyl chloride, or by the use of a reagent for forming activated esters, for
example N,N'-
dicyclohexylcarbodiimide {DCC) or N-ethyl-N'-(3-dimethylaminopropyl)-
carbodiimide (EDC)
of formula X. Where the compound of formula X is a halogenating agent, the
group X is,
for example, a leaving group, for example halogen, e.g. fluorine, bromine or
iodine or
especially chlorine, and W, is, for example, PCI2, SOCI, SOBr or CICOCO.
The operation is optionally carried out in an inert organic solvent, for
example in an
aliphatic, haiogenated aliphatic, aromatic or halogenated aromatic
hydrocarbon, for
example n-hexane, benzene, toluene, a xyiene, dichloromethane, 1,2-
dichloroethane or
chiorobenzene, at reaction temperatures in the range of from -20°C to
the reflux
temperature of the reaction mixture, preferably at from 40 to 150°C,
and in the presence of
a catalytic amount of N,N-dimethylformamide. Such reactions are known and
various
variations thereof in respect of the leaving group X are described in the
literature.
The compounds of formulae V, VII and IX (Reaction Scheme 3) are novel. They
are import-
ant intermediates for the synthesis of the compounds of formula If. The
invention therefore
relates also to those compounds.
The compounds of formula IV (Reaction Scheme 1 ) wherein Z, = C(Rs)R~, Z2 =
(W)~s, Z3 =
C(R6}R, and na = 0 are known and can be prepared in a manner analogous to that
described, for example, in US-A-5 006 150, WO 97/08164, DE-OS-3 818 958 and
DE-OS-3 902 818.
The compounds of formula IV (Reaction Scheme 1 ) wherein Z, = CH, Z2 = O, S or
-(CH2)"s-,
Z3 = CH and n4 = 2 are known and can be prepared in a manner analogous to that
described, for example, in EP-A-0 338 992.
The compounds of formula IV (Reaction Scheme 1 ) wherein Z, = CH2, Z2 =
CHNHR9, Z3 =
CH2 and n4 = 0 are known and can be prepared in a manner analogous to that
described,
for example, in EP-A-0 278 907.
The compounds of formula IV (Reaction Scheme 1 ) wherein Z, = NR,o, 22 = O, Z3
= C(Rs)R,
and na = 0 are known and can be prepared in a manner analogous to that
described, for
example, in WO 96/26192 and US-A-5 336 662.


CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
-37-
The compounds of formula IVa (Reaction Scheme 2) wherein R" and R,2 are as
defined for
formula I are known and can be prepared in a manner analogous to that
described, for
example, in WO 96/26206 and WO 97108164.
The compounds of formula V in Reaction Scheme 3 can be obtained in accordance
with
standard procedures, for example from the corresponding esters of formula
XXVII
R~
S(O)S O
R3 C. (XXVII),
OR2e
R5
wherein R, to R5 and n are as defined for formula I and R2B is C,-C4alkyl, for
example via
Claisen condensation, ar from the compounds of formula III by reaction with a
ketocarboxylic acid salt of formula XXVIII
COO - M +
CH (XXVIII),
2
~ COR~4
wherein R,4 is as defined for formula I and M+ is an alkali metal ion (see,
for example,
WO 96/26192, EP-A-0 496 631 ).
The salicylic acid derivatives of formula XX (Reaction Scheme 4) are either
known (some of
them being commercially available, for example when R5 is amino (4-
aminosalicylic acid)) or
can readily be prepared by standard procedures, for example starting from 4-
aminosalicylic
acid via diazotisation, Sandmeyer reaction and aromatic, nucleophilic
substitution (see e.g.
J. March, "Advanced Organic Chemistry", 4th Edition, John Wiley & Sons, New
York, 1992,
pages 641-676) or Heck reaction of the resulting halide.
The benzoic acid derivatives of formula XXa (Reaction Scheme 5) are either
known or can
readily be obtained by bromination of the corresponding benzoic acid
derivatives (see
Reaction Scheme 4, Route b)).
The reagents of formulae VI, VIII, X, XXV, XXVa, XXVb and XXVI used in
Reaction
Schemes 3 to 6 are either known or can be prepared analogously to disclosed
procedures.


CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
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For the preparation of all other compounds of formula I functionalised in
accordance with
the definitions of R, and R2 (2-position of the dihydrobenzo[b]thiophene
ring), a large
number of known standard procedures are available, for example alkylation,
halogenation,
acylation, amidation, oximation, oxidation and reduction, the choice of a
suitable
preparation process being governed by the properties (reactivities) of the
substituents in the
respective intermediates (see e.g. EP-A-0 796 856).
For the preparation of all other compounds of formula 1 functionalised in
accordance with
the definition of Re wherein Q is a group D, to Q4, a large number of known
standard
procedures are available, for example alkylation, acylation and treatment with
a sulfur
reagent (e.g. PzSS or Lawesson), the choice of a suitable preparation process
being
governed by the properties (reactivities) of the substituents in the
respective intermediates
(see e.g. WO 97/08164 and DE-OS-3 902 818).
All other compounds within the scope of formula I can readily be prepared,
taking into
account the chemical properties of the dihydrobenzo[b]thiophene or Q moiety in
relation to
the structure of the dihydrobenzo[b]thiophene or Q rings, in a manner
analogous to that
described in Preparation Examples P1 to P11 or, for example, to that described
in the
patent specifications indicated.
The end products of formula I can in conventional manner be isolated by
concentration or
evaporation of the solvent and purified by recrystallisation or trituration of
the solid residue
in solvents in which they are not readily soluble, such as ethers, aromatic
hydrocarbons or
chlorinated hydrocarbons, by distillation or by means of column chromatography
and a
suitable eiuant. The sequence in which it is advantageous to carry out certain
reactions in
order to avoid possible secondary reactions will also be familiar to the
person skilled in the
art. Unless the synthesis is specifically aimed at the isolation of pure
isomers, the product
may be obtained in the form of a mixture of two or more isomers. The isomers
can be
separated according to methods known per se.
For the use according to the invention of the compounds of formula I, or of
compositions
comprising them, there come into consideration all methods of application
customary in
agriculture, for example pre-emergence application, post-emergence application
and seed
dressing, and also various methods and techniques such as, for example, the
controlled
release of active ingredient. For that purpose a solution of the active
ingredient is applied to


CA 02291101 1999-11-24
WO 99109023 - 39 - PCT/EP98/05247
mineral granule carriers or polymerised granules (urea/forrnaldehyde) and
dried. If required,
it is also possible to apply a coating (coated granules), which allows the
active ingredient to
be released in metered amounts over a specific period of time.
The compounds of formula I may be used in unmodified form, that is to say as
obtained in
the synthesis, but they are preferably formulated in customary manner together
with the
adjuvants conventionally employed in formulation technology, for example into
emulsifiable
concentrates, directly sprayable or dilutabie solutions, dilute emulsions,
wettable powders,
soluble powders, dusts, granules or microcapsules. Such formulations are
described, for
example, on pages 9 to 13 of WO 97/34485. As with the nature of the
compositions, the
methods of application, such as spraying, atomising, dusting, wetting,
scattering or pouring,
are chosen in accordance with the intended objectives and the prevailing
circumstances.
The formulations, that is to say the compositions, preparations or mixtures
comprising the
compound (active ingredient) of formula I or at least one compound of formula
I and,
usually, one or more solid or liquid formulation adjuvants, are prepared in
known manner,
e.g. by homogeneously mixing and/or grinding the active ingredients with the
formulation
adjuvants, for example solvents or solid carriers. Surface-active compounds
(surfactants)
may also be used in addition in the preparation of the formulations. Examples
of solvents
and solid carriers are given, for example, on page 6 of WO 97134485.
Depending on the nature of the compound of formula I to be formulated,
suitable surface-
active compounds are non-ionic, cationic andlor anionic surfactants and
surtactant mixtures
having good emulsifying, dispersing and wetting properties. Examples of
suitable anionic,
non-ionic and cationic surfactants are listed, for example, on pages 7 and 8
of
W O 97134485.
In addition, the surfactants conventionally employed in formulation
technology, which are
described in, inter alia, "McCutcheon's Detergents and Emulsifiers Annual" MC
Publishing
Corp., Ridgewood New Jersey, 1981, Stache, H., "Tensid-Taschenbuch", Carl
Hanser
Verlag, Munich/Vienna 1981, and M, and J. Ash, "Encyclopedia of Surfactants",
Vol. I-III,
Chemical Publishing Co., New York, 1980-81, are also suitable for the
preparation of the
compositions according to the invention.
The herbicidal formulations generally contain from 0.1 to 99 % by weight,
especially from
0.1 to 95 % by weight, of herbicide, from 1 to 99.9 % by weight, especially
from 5 to 99.8


CA 02291101 1999-11-24
WO 99/09423 PCT/EP98/05247
-40-
by weight, of a solid or liquid formulation adjuvant, and from 0 to 25 % by
weight, especially
from 0.1 to 25 % by weight, of a surfactant. Whereas commercial products will
preferably be
formulated as concentrates, the end user will normally employ dilute
formulations. The
compositions may also comprise further ingredients, such as stabilisers, for
example vege-
table oils or epoxidised vegetable oils (epoxidised coconut oil, rape oil or
soybean oil), anti-
foams, for example silicone oil, preservatives, viscosity regulators, binders,
tackifiers, and
also fertilisers or other active ingredients.
The compounds of formula I can be used successfully either in the form of a
mixture of the
isomeric forms I, to 14 and Ic (Q is a group Q, to Qa and Re is OH) or 16, I,
and ie (4 is a
group Q5) or in the form of pure isomeric forms I, to 14 or Ic, or I6, I, or
le, generally on plants
or the locus thereof, at rates of application of from 0.001 to 4 kg/ha,
especially from 0.005
to 2 kg/ha. The concentration required to achieve the desired effect can be
determined by
experiment. It is dependent on the nature of the action, the stage of
development of the
cultivated plant and of the weed and on the application (place, time, method)
and may vary
within wide limits as a function of those parameters.
The compounds of formula I are distinguished by herbicidal and growth-
inhibiting properties,
allowing them to be used in crops of useful plants, especially cereals,
cotton, soybeans,
sugar beet, sugar cane, plantation crops, rape, maize and rice, and also for
non-selective
weed control. The term "crops" is to be understood as including also crops
that have been
made tolerant to herbicides or classes of herbicides as a result of
conventional methods of
breeding or genetic techniques. The weeds to be controlled may be either
monocotyl-
edonous or dicotyledonous weeds, such as, for example, Stellaria, Nasturtium,
Agrostis,
Digitaria, Avena, Setaria, Sinapis, Lolium, Solanum, Phaseolus, Echinochloa,
Scirpus,
Monochoria, Sagittaria, Bromus, Alopecurus, Sorghum halepense, Rottboellia,
Cyperus,
Abutilon, Sida, Xanthium, Amaranthus, Chenopodium, Ipomoea, Chrysanthemum,
Galium,
Viola and Veronica.
The following Examples further illustrate but do not limit the invention.


CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
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Preparation Examples:
Example P1: 2-All~rlox~r-4-chlorobenzoic acid methyl ester
O o
~i
C~OCH3
CI
50 g (0.36 mol) of potassium carbonate are added, with stirring, to 56 g (0.3
mol) of 4-
chforosalicylic acid methyl ester in 200 ml of dimethyl sulfoxide. When the
slightly
exothermic reaction has subsided, 40 g (0.33 mol) of allyl bromide are added
dropwise at
25°C. The reaction mixture is stirred at 22°C for 16 hours,
poured into water and extracted
by shaking with diethyl ether. The combined ether phases are washed with
water, dried
with sodium sulfate and concentrated by evaporation. The residue is
recrystallised from a
small amount of hexane. 62 g (91.2 % of theory) of the desired product having
a melting
point of 61-62°C are obtained.
Example P2: 2-Hydroxy-3-yproneny,-4-chlorobenzoic acid methyl ester
OH O
~I
C"OCH3
CI
97.9 g (0.432 mol) of 2-aliyloxy-4-chlorobenzoic acid methyl ester (Example P1
) are melted
in a round-bottomed flask and irradiated in a microwave oven at 500 watts for
5 minutes. An
exothermic reaction takes place. The reaction mixture is allowed to cool and
yields 97.1 g
(99.1 % of theory) of the desired product having a melting point of 32-35'C.


CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
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Example P3' 2-Oxv-(N.N-dimethvl-thiocarbamovll-3-(3-propenyl)-4-chlorobenzoic
acid
meths ester
CH3
N.,CH3
S
O O
ii
C'OCH3
CI
97 g (0.428 mol) of 2-hydroxy-3-(3-propenyl)-4-chlorobenzoic acid methyl ester
(Example P2) and 69 g (0.5 mol) of potassium carbonate are stirred in 400 ml
of dimethyl-
formamide for 1/2 hour. A solution of 55.6 g (0.45 mol) of N,N-dimethyl-
thiocarbamoyl
chloride in 200 ml of dimethylformamide is then added dropwise thereto. The
reaction
mixture is stirred at 22°C for 22 hours. To complete the reaction, 11 g
(0.09 mol) of N,N-
dimethyl-thiocarbamoyl chloride and 15 g (0.11 mol) of potassium carbonate are
added.
After a further 24 hours at 22°C, the reaction mixture is poured into
an ice-water mixture
and extracted by shaking with ethyl acetate. The ethyl acetate phase is washed
with water,
then with brine, dried over sodium sulfate and concentrated by evaporation.
The residue is
chromatographed on silica gel {eluant: ethyl acetate/hexane 1J3), yielding
114.5 g (85 % of
theory) of the desired product in the form of an oil.
Example P4: 2-Merc~to-~N.N-dimethyl-carbamoyl)-3-(3-proaen~)-4-chlorobenzoic
acid
methyl ester
CH3
N~CH3
O
S O
II
C'OCH3
CI
114.5 g (0.365 mol) of 2-oxy-(N,N-dimethyl-thiocarbamoyl)-3-(3-propenyl)-4-
chlorobenzoic
acid methyl ester (Example P3) dissolved in 150 ml of Biphenyl ether are added
dropwise,
in the course of 5 hours, to 100 ml of Biphenyl ether at 205-210'C. The
temperature is
maintained at 205°C for a further 1 1/2 hours. After cooling, the
Biphenyl ether is distilled


CA 02291101 1999-11-24
WO 99/09023 - 43 - PCTIEP98/05247
off at a pressure of 0.04 mbar. The residue is chromatographed on silica gel
(eluant: ethyl
acetate/hexane 1/1 }, yielding 90.2 g (78.8 % of theory) of the desired
product in the form of
an oil.
Example P5' 4-Chloro-2-methyl-2 3-dihydro-benzofblthiophene-7-carboxvfic acid
CH3
S
COON (Comp. No. 1.001 )
CI
90.2 g (0.287 mol) of 2-mercapto-(N,N-dimethylcarbamoyl)-3-(3-propenyl)-4-
chlorobenzoic
acid methyl ester (Example P4) is heated under reflux for 20 hours in 150 ml
of acetic acid
and 200 ml of concentrated hydrochloric acid. The reaction mixture is
concentrated in a
rotary evaporator and the residue is stirred with water and cooled. The solid
substance is
filtered off and drying is carried out in vacua at 60~C, yielding 66 g (100 %
of theory) of the
expected product having a melting point of 215-218~C.
Example P6: 4-Chloro-2-methyl-1.1-dioxo-2.3-dihydro-benzo(b]thiophene-7-carbox
IiY c acid
CH3 O
a
S=O
COON (Comp. No. 1.027)
CI
20 g (0.0875 mol) of 4-chloro-2-methyl-2,3-dihydro-benzo[b]thiophene-7-
carboxylic acid
(Example P5) are suspended in 150 ml of acetic acid and heated to 70°C.
24 ml of approx.
35 % hydrogen peroxide are then added dropwise thereto. The reaction is
exothermic. At
80°C, the heating bath is removed and the dropwise addition is
continued in such a manner
that the temperature remains at 80'C. The reaction mixture is then maintained
at 70-75°C
for 1 hour. The reaction mixture is then concentrated using a rotary
evaporator until crystals
are deposited. Water is then added; the mixture is cooled and the precipitated
crystals are
filtered off. After drying in vacuo at 60 C, 17 g (74 % of theory) of the
desired product
having a melting point of 223-225'C are obtained.
*rB


CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
-44-
Example P7: 4-Chloro-2-methyl-1.1-dioxo-2.3-dihYdro-benzofblthiophene-7-
carboxylic acid
chloride
CH3 O
S=O
COCI
i
CI
16.7 g (0.06 mol) of 4-chloro-2-methyl-1,1-dioxo-2,3-dihydro-benzo[b]thiophene-
7-carboxylic
acid (Example P6) are heated to 90°C in 100 ml of toluene. 3 drops of
dimethylformamide
are added and then 9.5 g (0.08 mol) of thionyl chloride are added dropwise
thereto in the
course of 20 minutes, a clear solution being obtained. The reaction mixture is
heated at
100°C for 3 hours and then concentrated by evaporation using a rotary
evaporator, yielding
17 g of the desired product in the form of a solid substance.
Example P8: (2.3-Dihydro-4-chloro-2-methylbenzofblthiot~hen-7-yl)l2-hvdroxy-6-
oxo-1-
~clohexen-1-ylLmethanone S.S-dioxide
O CH3
O O O~S
(Comp. No. 2.027)
OH CI
9.5 g (0.094 mol) of triethylamine are added at 5°C to 3.6 g (0.0314
mol) of 1,3-
cyclohexanedione in 80 ml of methylene chloride. At 5'C, 8.8 g (0.0314 mol) of
4-chloro-2-
methyl-1,1-dioxo-2,3-dihydro-benzo[b]thiophene-7-carboxylic acid chloride
(Example P7) in
20 ml of methyiene chloride are added dropwise. After 1 hour at 22°C,
0.5 ml of acetone
cyanohydrin are added. After 5 1/2 hours, the reaction mixture is extracted by
shaking with
2N hydrochloric acid. The methylene chloride phase is separated off, dried
with sodium
sulfate and concentrated by evaporation, and the residue is dissolved in a
small amount of
warm acetone. On being left to stand the product crystallises out. After
filtration, 5.5 g (50
of theory) of the expected product having a melting point of 170-172°C
are obtained.


CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
-45-
Example P9' 4-Chloro-2-methyl-2 3-dihydro-benzo(bjthiophene-7-carboxvltc acid
chloride
CH3
S
COCI
i
i
cl
45.7 g (0.2 mol) of 4-chloro-2-methyl-2,3-dihydro-benzo[bjthiophene-7-
carboxylic acid
(Example P5), 23.8 g (0.22 mol) of thionyl chloride and a few drops of
dimethylformamide
are heated in 300 ml of toluene at 100°C for 18 hours. Concentration by
evaporation yields
the desired product, which can be used further without purification.
Examale P10~ (2 3-Dihydro-4-chloro-2-methvlbenzo~blthiot'hen-7-
vl)(1.3=dimethyl-5-
~drox~i H-pyrazol-4-yl)methanone
CH3
(Comp. No. 10.001 )
CI
2.3 g (0.02 mot) of 1,3-dimethylpyrazolone-5 and 2.2 g (0.022 mol) of
triethylamine are
suspended in 80 ml of ethyl acetate and cooled to 5°C, and then 5.0 g
(0.02 mol) of 4-
chloro-2-methyl-2,3-dihydro-benzo[bjthiophene-7-carboxylic acid chloride
(Example P9) in
20 ml of ethyl acetate are added. The reaction mixture is stirred at
22°C for 18 hours, the
salts are filtered off and concentration by evaporation is carried out using a
rotary
evaporator. The residue is dissolved in 70 ml of dimethyiformamide, and 2.2 g
(0.022 mol)
of triethylamine and 0.2 g of potassium cyanide are added. The reaction
mixture is left to
stand at 22°C for 18 hours and the dimethylformamide is evaporated off.
Ethyl acetate and
m1 of glacial acetic acid are added to the residue and the resulting solution
is extracted by
shaking with water. The organic phase is separated off, dried with sodium
sulfate and
concentrated by evaporation. Trituration with diethyl ether yields the desired
product having
a melting point of 191-193°C.
_ _ CH"


CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
-46-
Examele P11 ~ 12.3-Dihvdro-4-chloro-2-meth Ibenzojb]thiophen-7-vll(1.3-
dimethyl-5-
~droxv-1 H-nyrazol-4-YI)methanone S.S-dioxide
CH3 N
(Comp. No. 10.027)
2.0 g (0.0115 mol) of 3-chloroperbenzoic acid dissolved in 30 ml of methylene
chloride are
added to 1.7 g (0.0052 mol) of (2,3-dihydro-4-chloro-2-methylbenzo(b]thiophen-
7-yl)(1,3-
dimethyl-5-hydroxy-1 H-pyrazol-4-yl)methanone (Example P10) in 40 ml of
methylene
chloride. The reaction mixture is left to stand at 22°C for 2 days and
is extracted by shaking
with saturated, aqueous sodium hydrogen carbonate solution. The hydrogen
carbonate
phase is acidified with concentrated hydrochloric acid and the resulting
precipitate is filtered
off. The solid substance so obtained is triturated with diethyl ether and
isolated by filtration,
yielding 1.6 g of the desired product having a melting point of 230-233 C.
In analogous manner, and in accordance with methods such as those described in
the
general Reaction Schemes 1 to 5 and the references indicated therein, it is
also possible to
prepare the preferred compounds listed in the following Tables.
Table 1: A preferred group of compounds of formula I corresponds to general
formula Id
R~
RZ S(O)" O
R (Id}, wherein the meanings of the corresponding substituents
OH
4
R~
R, to R5 and n are given in Table A, so that 819 specific compounds of formula
Id are
disclosed.
_ . CH~


CA 02291101 1999-11-24
WO 99/09023 PCTIEP98/05247
-47-
Table 2: A further preferred group of compounds of formula I corresponds to
general
R,
R2
S(O}~ O O
formula Ig R3 (Ig), wherein the meanings of the corresponding
Ra
R5 OH
substituents R, to R5 and n are given in Table A, so that 819 specific
compounds of
formula Ig are disclosed.
Table 3: A further preferred group of compounds of formula I corresponds to
general
S(O}~ O OH
formula Ih R3 (Ih), wherein the meanings of the corresponding
R
' ~~~ CH2
R5 O
substituents R, to RS and n are given in Table A, so that 819 specific
compounds of
formula Ih are disclosed.
Table 4: A further preferred group of compounds of formula I corresponds to
general
R~
R2 S(O}~ O OH
formula li R3 ~ ~ (li}, wherein the meanings of the corresponding
R4
R5 O
substituents R, to RS and n are given in Table A, so that 819 specific
compounds of
formula li are disclosed.
Table 5: A further preferred group of compounds of formula I corresponds to
general
R,
R2 S(O)~ O O
formula Ij R3 (Ij), wherein the meanings of the
Ra
R OH NH CH3
corresponding substituents R, to R5 and n are given in Table A, so that 819
specific
compounds of formula ij are disclosed.


CA 02291101 1999-11-24
WO 99109023 PCTIEP98105247
-48-
Table 6: A further preferred group of compounds of formula I corresponds to
general
R,
R2 g(O)~ p OH
R3 CH3
formula Ik R ~ ~ (Ik), wherein the meanings of the
a ~ ~ I 'CH3
N.O
RS O
CH3
corresponding substituents R, to R5 and n are given in Table A, so that 819
specific
compounds of formula Ik are disclosed.
Table A
Compd.Rz R, R3 R4 RS n


No.


.001 H CH3 H H CI 0


.002 H CH3 H H F 0


.003 H CH3 H H Br 0


.004 H CH3 H H SOZMe 0


.005 H CH3 H H SMe 0


.006 H CH3 H H S02NMe2 0


.007 H CH3 H H CF3 0


.008 H CH3 H H CH3 0


.009 H CH3 H H CH(CH3)20


.010 H CH3 H H N02 0


.011 H CH3 H H OCH3 0


.012 H CH3 H H OCF2CF3 0


.013 H CH3 H H CN 0


.014 H CH3 H H CI i


.015 H CH3 H H F 1


.016 H CH3 H H Br 1


.017 H CH3 H H S02Me 1


.018 H CH3 H H SMe 1


.019 H CH3 H H S02NMe2 1


.020 H CH3 H H CF3 1



CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
-49-
Compd.R2 R~ R3 R4 Rs


No.


.021 H CH3 H H CH3 1


.022 H CH3 H H CH(CH3)21


.023 H CH3 H H NOZ 1


.024 H CH3 H H OCH3 1


.025 H CH3 H H OCF2CF3 1


.026 H CH3 H H CN 1


.027 H CH3 H H CI 2


.028 H CH3 H H F 2


.029 H CH3 H H Br 2


.030 H CH3 H H S02Me 2


.031 H CH3 H H SMe 2


.032 H CH3 H H S02NMez 2


.033 H CHa H H CF3 2


.034 H CH3 H H CH3 2


.035 H CH3 H H CH(CH3)22


.036 H CH3 H H N02 2


.037 H CH3 H H OCH3 2


.038 H CH3 H H OCF2CF3 2


.039 H CH3 H H CN 2


.040 H CH3CH2 H H CI 0


.041 H CH3CH2 H H F 0


.042 H CH3CH2 H H Br 0


.043 H CH3CH2 H H SOZMe 0


.044 H CH3CH2 H H SMe 0


.045 H CH3CH2 H H S02NMe2 0


.046 H CH3CH2 H H CF3 0


.047 H CH3CH2 H H CH3 0
-


.048 H CH3CH2 H H CH(CH3)z0


.049 H CH3CH2 H H N02 0


.050 H CH3CH2 H H OCH3 0


.051 H CH3CH2 H H OCF2CF3 0



CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
-50-
Compd. Rz R, R3 Ra R$ n


No.


.052 H CH3CHz H H CN 0


.053 H CH3CHz H H CI 1


.054 H CH3CHz H H F 1


.055 H CH3CHz H H Br 1


.056 H CH3CHz H H S02Me 1


.057 H CH3CHz H H SMe 1


.058 H CH3CHz H H S02NMez 1


.059 H CH3CHz H H CFs 1


.060 H CH3CHz H H CH3 1


.061 H CH3CHz H H CH(CH3)z1


.062 H CH3CHz H H NOz 1


.063 H CH3CHz H H OCH3 1


.064 H CH3CHz H H OCF2CF3 1


.065 H CH3CH2 H H CN 1


.066 H CHaCHz H H CI 2


.067 H CH3CHz H H F 2


.068 H CHaCHz H H Br 2


.069 H CH3CHz H H S02Me 2


.070 H CH3CHz H H SMe 2


.071 H CH3CHz H H S02NMez 2


.072 H CH3CHz H H CF3 2


.073 H CH3CHz H H CH3 2


.074 H CHsCHz H H CH(CH3)z2


.075 H CH3CHz H H NOz 2


.076 H CH3CHz H H OCH3 2


.077 H CH3CHz H H OCFZCF3 2


.078 H CH3CHz H H CN 2


.079 CH3 CH3CHz H H CI 0


.080 CH3 CH3CHz H H F 0


.081 CH3 CH3CHz H H Br 0


.082 CH3 CH3CHz H H S02Me 0



CA 02291101 1999-11-24
WO 99109023 PCTIEP98105247
-51 -
Compd. R2 R, R3 R4 R5 n


No.


.083 CHs CH3CH2 H H SMe 0


.084 CHs CH3CH2 H H S02NMez 0


.085 CHs CH3CH2 H H CFs 0


.086 CHs CH3CH2 H H CHs 0


.087 CHs CH3CH2 H H CH(CHs)2 0


.088 CHs CH3CH2 H H N02 0


.089 CHs CH3CH2 H H OCHs 0


.090 CHs CH3CH2 H H OCF2CFs 0


.091 CHs CH3CH2 H H CN 0


.092 CHs CH3CH2 H H CI 1


.093 CHs CH3CH2 H H F 1


.094 CHs CH3CH2 H H Br 1


.095 CHs CH3CH2 H H S02Me 1


.096 CHs CH3CH2 H H SMe 1


.097 CHs CH3CHz H H S02NMe2 1


.098 CHs CH3CH2 H H CFs 1


.099 CHs CH3CH2 H H CHs 1


.100 CHs CH3CH2 H H CH(CHs)2 1


.101 CHs CH3CH2 H H NOZ 1


.102 CHs CH3CH2 H H OCHs 1


.103 CHs CH3CH2 H H OCFZCFs 1


.104 CHs CH3CH2 H H CN 1


.105 CHs CH3CH2 H H CI 2


.106 CHs CH3CH2 H H F 2


.107 CHs CH3CH2 H H Br 2


.108 CHs CH3CH2 H H S02Me 2


.109 CHs CH3CH2 H H SMe 2


.110 CHs CH3CHZ H H S02NMe2 2


.111 CHs CH3CH2 H H CFs 2


.112 CHs CH3CHZ H H CHs 2


.113 CHs CH3CH2 H H CH(CHs)2 2



CA 02291101 1999-11-24
WO 99!09023 PCT/EP98/05247
-52-
Compd. R2 R, Rs R4 Rs n


No.


.114 CHs CH3CHz H H N02 2


.115 CHs CH3CH2 H H OCHs 2


.116 CHs CH3CH2 H H OCF2CFs2


.117 CHs CH3CH2 H H CN 2


.118 H CHs H CHs CI 0


.119 H CHs H CHs F 0


.120 H CHs H CHs Br 0


.121 H CHs H CHs S02Me 0


.122 H CHs H CHs SMe 0


.123 H CHs H CHs SOZNMe20


.124 H CHs H CHs CFs 0


.125 H CHs H CHs CHs 0


.126 H CHs H CHs CH(CHs)20


.127 H CHs H CHs N02 0


.128 H CHs H CHs OCHs 0


.129 H CHs H CHs OCF2CFs0


.130 H CHs H CHs CN 0


.131 H CHs H CHs CI 1


.132 H CHs H CHs F 1


.133 H CHs H CHs Br 1


.134 H CHs H CHs S02Me 1


.135 H CHs H CHs SMe 1


.136 H CHs H CHs S02NMe21


.137 H CHs H CHs CFs 1


.138 H CH3 H CH3 CHs 1


.139 H CHs H CHs CH(CHs)21


.14o H CHs H CHs N02 1


.141 H CHs H CHs OCHs 1


.142 H CHs H CH3 OCFZCFs1


.143 H CHs H CHs CN 1


.144 H CHs H CHs CI 2



CA 02291101 1999-11-24
WO 99/09023 PCT/EP98I05247
-53-
Compd.R2 R, R3 Ra R5 n


No.


.145 H CHs H CHs F 2


.146 H CHs H CHs Br 2


.147 H CHs H CHs S02Me 2


.i48 H CHs H CHs SMe 2


.149 H CHs H CHs S02NMe2 2


.150 H CHs H CHs CFs 2


.I51 H CHs H CHs CHs 2


.152 H CHs H CHs CH(CHs)22


.153 H CHs H CHs N02 2


.154 H CHs H CHs OCHs 2


.155 H CHs H CHs OCF2CFs 2


.156 H CH3CH2 H CHs CN 2


.157 H CH3CH2 H CHs CI 0


.158 H CH3CH2 H CHs F 0


.159 H CH3CH2 H CHs Br 0


.160 H CH3CH2 H CHs S02Me 0


.161 H CH3CH2 H CHs SMe 0


.162 H CH3CHz H CHs S02NMe2 0


.163 H CH3CH2 H CHs CFs 0


.164 H CH3CH2 H CHs CHs 0


.165 H CH3CHz H CHs CH(CHs)20


.166 H CH3CH2 H CHs N02 0


.167 H CH3CH2 H CHs OCHs 0


.168 H CH3CH2 H CHs OCF2CFs 0


.169 H CH3CH2 H CHs CN 0


.170 H CH3CH2 H CHs CI 1


.171 H CH3CHz H CHs F 1


.172 H CH3CH2 H CHs Br 1


.173 H CH3CH2 H CHs SO2Me 1


.1?4 H CH3CH2 H CH3 SMe 1


.175 H CH3CH2 H CHs S02NMe2 1



CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/0524'7
-54-
Compd.RZ R, R3 Ra Rs n


No.


.176 H CH3CH2 H CH3 CF3 1


.177 H CHaCH2 H CH3 CHa 1


.178 H CH3CH2 H CH3 CH(CH3)21


.179 H CH3CH2 H CH3 NOZ i


.180 H CH3CH2 H CH3 OCH3 1


.181 H CH3CH2 H CH3 OCF2CF3 1


.182 ~ H CH3CH2 H CH3 CN 1


.183 H CH3CH2 H CH3 CI 2


.184 H CH3CH2 H CH3 F 2


.185 H CH3CH2 H CH3 Br 2


.186 H CH3CH2 H CH3 S02Me 2


.187 H CH3CH2 H CH3 SMe 2


1 gg H CH3CH2 H CH3 S02NMe2 2


.189 H CH3CH2 H CH3 CF3 2


.190 H CH3CH2 H CH3 CH3 2


.191 H CH3CH2 H CH3 CH(CHa)22


.192 H CH3CH2 H CH3 N02 2


.193 H CH3CHz H CN3 OCH3 2


.194 H CH3CHz H CH3 OCF2CF3 2


.195 H CH3CH2 H CH3 CN 2


.196 CH3 CH3CH2 H CH3 CI 0


.197 CH3 CH3CH2 H CH3 F 0


.198 CH3 CH3CH2 H CH3 Br 0


.199 CH3 CH3CH2 H CH3 S02Me 0


.200 CH3 CH3CH2 H CH3 SMe 0


.201 CH3 CH3CH2 H CH3 SOzNMe2 0


.202 CH3 CH3CHz H CH3 CF3 0


.203 CH3 CH3CH2 H CH3 CH3 0


.204 CH3 CH3CHz H CH3 CH(CH3)20


.205 CH3 CH3CH2 H CH3 N02 0


.206 CH3 CH3CH2 H CH3 OCH3 0




CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
-55-
Compd.R2 R~ R3 R4 Rs


No.


.207 CH3 CH3CH2 H CH3 OCF2CF3 0


.208 CH3 CH3CH2 H CH3 CN 0


.209 CH3 CH3CH2 H CH3 CI 1


.210 CH3 CH3CH2 H CH3 F 1


.211 CH3 CH3CH2 H CH3 Br 1


.212 CH3 CH3CH2 H CH3 S02Me 1


.213 CH3 CH3CH2 H CH3 SMe 1


.214 CH3 CH3CH2 H CH3 S02NMe2 1


.215 CH3 CH3CH2 H CH3 CF3 1


.216 CH3 CH3CH2 H CH3 CH3 1


.217 CH3 CH3CH2 H CH3 CH(CH3}21


.218 CH3 CH3CH2 H CH3 N02 1


.219 CHs CH3CH2 H CHs OCH3 1


.220 CH3 CH3CH2 H CH3 OCF2CF3 1


.221 CH3 CH3CH2 H CHs CN 1


.222 CH3 CH3CH2 H CH3 CI 2


.223 CH3 CH3CH2 H CH3 F 2


.224 CH3 CH3CH2 H CH3 Br 2


.225 CH3 CH3CH2 H CH3 S02Me 2


.226 CH3 CH3CHz H CH3 SMe 2


.227 CH3 CH3CH2 H CH3 S02NMe2 2


.228 CH3 CH3CH2 H CH3 CF3 2


.229 CH3 CH3CH2 H CH3 CH3 2


.230 CH3 CH3CH2 H CH3 CH(CH3)22


.231 CH3 CH3CH2 H CH3 N02 2


.232 CH3 CH3CH2 H CH3 OCH3 2


.233 CH3 CH3CH2 H CH3 OCF2CF3 2


.234 CH3 CH3CH2 H CH3 . CN 2


.235 CH3 CH3CH2 CH3 CH3 CI 0


.236 CH3 CH3CH2 CH3 CH3 F 0


.237 CH3 CH3CH2 CH3 CH3 Br 0




CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
-56-
Compd. Rz R, Rs R4 R5 n


No.


.238 CHs CH3CHz CHs CHs S02Me 0


.239 CHs CH3CHz CHs CHs SMe 0


.240 CHs CH3CHz CHs CHs SOZNMez0


.241 CHs CH3CHz CHs CHs CFs 0


.242 CHs CH3CHz CHs CHs CHs 0


.243 CH3 CH3CHz CH3 CHs CH(CH3)z0


.244 CHs CH3CHz CHs CHs NOz 0


.245 CHs CH3CHz CHs CHs OCHs 0


.246 CHs CH3CHz CHs CHs OCFZCF30


.247 CH3 CH3CHz CHs CH3 CN 0


.248 CHs CH3CHz CHs CHs CI 1


.249 CHs CH3CHz CHs CHs F 1


.250 CHs CH3CHz CHs CHs Br 1


.251 CHs CH3CHz CH3 CHs S02Me i


.252 CHs CH3CHz CHs CHs SMe 1


.253 CHs CH3CHz CHs CHs S02NMez1


.254 CHs CH3CHz CHs CHs CFs 1


.255 CHs CH3CHz CHs CHs CHs 1


.256 CHs CH3CHz CHs CHs CH(CHs)z1


.257 CHs CH3CHz CHs CHs NOz 1


.258 CH3 CH3CHz CHs CHs OCHs 1


.259 CHs CH3CHz CHa CH3 OCF2CFs1


.260 CHs CH3CHz CHs CHs CN 1


.261 CHs CH3CHz CHs CHs CI 2


.262 CH3 CH3CHz CHs CH3 F 2


.263 CHs CH3CHz CHs CHs Br 2


.264 CHs CHsCHz CHs CH3 S02Me 2


.265 CHs CHsCHz CHs CHs SMe 2


.266 CHs CHsCHz CHs CH3 S02NMez2


.267 CHs CH3CHz CHs CHs CFs 2


.268 CHs CH3CHz CHs CHs 2
CHs



CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
-57-
Compd. Rz R, R3 Re RS


No.


.269 CH3 CH3CHz CH3 CH3 CH(CH3)z2


.270 CH3 CH3CHz CH3 CH3 NOz 2


.271 CH3 CH3CHz CH3 CH3 OCH3 2


.272 CH3 CH3CHz CH3 CH3 OCFZCF3 2


.273 CH3 CH3CHz CH3 CH3 CN 2


.274 H CH3 H CI CI 0


.275 H CH3 H CI F 0


.276 H CH3 H CI Br 0


.277 H CH3 H CI S02Me 0


.278 H CH3 H CI SMe 0


.279 H CH3 H CI S02NMe2 0


.280 H CH3 H CI CF3 0


.281 H CH3 H CI CH3 0


.282 H CH3 H CI CH(CH3)z0


.283 H CH3 H CI NOz 0


.284 H CH3 H CI OCH3 0


.285 H CH3 H CI OCF2CF3 0


.286 H CH3 H CI CN 0


.287 H CH3 H CI CI 1


.288 H CH3 H CI F 1


.289 H CH3 H CI Br 1


.290 H CH3 H CI S02Me 1


.291 H CH3 H CI SMe 1


.292 H CH3 H CI S02NMez 1


.293 H CH3 H CI CF3 1


.294 H CH3 H CI CH3 1


.295 H CH3 H CI CH(CH3)z1


.296 H CH3 H CI NOz 1


.297 H CH3 H CI OCH3 1


.298 H CH3 H CI OCF2CF3 1


.299 H CH3 H CI CN 1



CA 02291101 1999-11-24
WO 99/09023 PCTIEP98105247
-58-
Compd. R2 R, R3 R4 R5 n


No.


,300 H CH3 H CI CI 2


.301 H CH3 H CI F 2


.302 H CH3 H CI Br 2


.303 H CH3 H CI S02Me 2


.304. H CH3 H CI SMe 2


.305 H CH3 H CI SOZNMe2 2


.306 H CH3 H CI CF3 2


.307 H CH3 H CI CH3 2


.308 H CH3 H Cl CH(CH3)22


.309 H CH3 H CI N02 2


.310 H CH3 H CI OCH3 2


.311 H CH3 H CI OCF2CF3 2


.3I2 H CH3 H CI CN 2


.313 H CH3CH2 H CI CI 0


.314 H CH3CH2 H CI F 0


.315 H CH3CH2 H CI Br 0


.316 H CH3CH2 H CI S02Me 0


.31? H CHsCH2 H CI SMe 0


.318 H CH3CH2 H CI S02NMe2 0


.319 H CH3CH2 H CI CF3 0


.320 H CH3CH2 H CI CH3 0


.321 H CH3CH2 H CI CH(CH3)20


.322 H CH3CH2 H CI N02 0


.323 H CH3CH2 H CI OCH3 0


.324 H CH3CH2 H CI OCF2CF3 0


.325 H CH3CH2 H CI CN 0


.326 H CH3CH2 H CI CI 1


.327 H CH3CH2 H CI F 1


.328 H CH3CH2 H CI Br 1


.329 H CH3CH2 H Cl SOzMe 1


.330 H CH3CH2 H CI SMe 1



CA 02291101 1999-11-24
WO 99/09023 PCT/EP98I05247
_Sg_
Compd.R2 R, R3 R4 RS n


No.


.331 H CH3CH2 H CI S02NMe2 1


.332 H CH3CH2 H CI CF3 1


.333 H CH3CH2 H CI CH3 1


.334 H CH3CH2 H CI CH(CH3)2 1


.335 H CH3CH2 H CI N02 1


.336 H CH3CH2 H Cl OCH3 1


.337 H CH3CH2 H CI OCF2CF3 1


.338 H CH3CH2 H CI CN 1


.339 H CH3CH2 H CI CI 2


.340 H CH3CH2 H CI F 2


.341 H CH3CH2 H CI Br 2


.342 H CH3CH2 H CI S02Me 2


.343 H CH3CH2 H CI SMe 2


.344 H CH3CH2 H CI S02NMe2 2


.345 H CH3CHz H CI CF3 2


.346 H CH3CH2 H CI CH3 2


.347 H CH3CH2 H CI CH(CH3)2 2


.348 H CH3CH2 H CI N02 2


.349 H CH3CH2 H CI OCH3 2


.350 H CH3CH2 H CI OCFZCF3 2


.351 H CH3CH2 H C! CN 2


.352 CH3 CH3CH2 H CI CI 0


.353 CH3 CH3CH2 H CI F 0


.354 CH3 CH3CH2 H CI Br 0


.355 CH3 CH3CH2 H CI S02Me 0


.356 CH3 CH3CH2 H CI SMe 0


.357 CH3 CHsCH2 H CI S02NMe2 0


.358 CH3 CH3CH2 H CI CF3 0


.359 CH3 CH3CH2 H CI CH3 0


.360 CH3 CH3CH2 H Cl CH(CH3)2 0


.361 CH3 CH3CH2 H CI N02 0



CA 02291101 1999-11-24
WO 99/09023 PCTIEP98/05247
-60-
Compd. R2 R, R3 R4 R5 n


No.


.362 CH3 CHsCHz H CI OCHs 0


.363 CH3 CH3CH2 H CI OCF2CF3 0


.364 CH3 CH3CH2 H CI CN 0


.365 CH3 CH3CH2 H CI CI 1


.366 CH3 CH3CH2 H CI F 1


.367 CH3 CH3CH2 H CI Br 1


.368 CHa CH3CH2 H CI S02Me 1


.369 CH3 CH3CH2 H CI SMe 1


.370 CH3 CH3CH2 H CI S02NMe2 1


.371 CH3 CH3CH2 H CI CF3 1


.372 CH3 CH3CHz H CI CH3 1


.373 CH3 CH3CH2 H Cl CH(CH3)21


.374 CH3 CH3CH2 H CI N02 1


.375 CH3 CH3CH2 H CI OCH3 1


.376 CH3 CH3CH2 H CI OCFZCF3 1


.377 CH3 CH3CH2 H CI CN 7


.378 CH3 CH3CH2 H CI CI 2


.379 CH3 CH3CH2 H CI F 2


.380 CH3 CH3CHz H CI Br 2


.381 CH3 CH3CHz H CI S02Me 2


.382 CH3 CH3CH2 H CI SMe 2


.383 CH3 CH3CH2 H CI S02NMe2 2


.384 CH3 CH3CH2 H CI CF3 2


.385 CH3 CH3CH2 H CI CH3 2


.386 CH3 CH3CH2 H CI CH(CH3)22


.387 CH3 CH3CH2 H CI NOZ 2


.388 CH3 CH3CH2 H CI OCH3 2


.389 CH3 CH3CH2 H CI OCF2CF3 2


.390 CH3 CH3CH2 H CI CN 2


.391 H CH3 H H CI 0


.392 H CH3 H H F 0



CA 02291101 1999-11-24
WO 99/09023 PCTIEP98/05247
-61 -
Compd.R2 R, R3 R4 R3 n


No.


.393 H CH3 H H Br 0


.394 H CH$ H H S02Me 0


.395 H CH3 H H SMe 0


.396 H CH3 H H S02NMe2 0


.397 H CH3 H H CF3 0


.398 H CH3 H H CH3 0


.399 H CH3 H H CH(CH3)20


.400 H CH3 H H N02 0


.401 H CH3 H H OCH3 0


.402 H CH3 H H OCF2CF3 0


.403 H CH3 H H CN 0


.404 H CH3 H H CI 1


.405 H CH3 H H F 1


.406 H CH3 H H Br 1


.407 H CH3 H H S02Me 1


.408 H CH3 H H SMe 1


.409 H CH3 H H S02NMe2 1


.410 H CH3 H H CF3 1


.411 H CH3 H H CH3 1


.412 H CH3 H H CH(CH3)21


.413 H CH3 H H NOZ 1


.414 H CH3 H H OCH3 1


.415 H CH3 H H OCF2CF3 1


.416 H CH3 H H CN 1


.417 H CH3 H H CI 2


.418 H CH3 H H F 2


.419 H CH3 H H Br 2


.420 H CH3 H H S02Me 2


.421 H CH3 H H SMe 2


.422 H CH3 H H S02NMe2 2


.423 H CH3 H H CF3 2



CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
-62-
Compd. R2 R, Rs Re R5 n


No.


.424 H CH3 H H CH3 2


.425 H CH3 H H CH(CH3)22


.426 H CH3 H H N02 2


.427 H CH3 H H OCH3 2


.428 H CH3 H H OCF2CF3 2


.429 H CH3 H H CN 2


.430 H CHZOH H H CI 0


.431 H CH20H H H F 0


.432 H CH20H H H Br 0


.433 H CHZOH H H S02Me 0


.434 H CH20H H H SMe 0


.435 H CH2OH H H S02NMe2 0


.436 H CH20H H H CF3 0


.437 H CH20H H H CH3 0


.438 H CH20H H H CH(CH3)20


.439 H CH20H H H N02 0


.440 H CH20H H H OCH3 0


.441 H CH20H H H OCF2CF3 0


.442 H CH20H H H CN 0


.443 H CH20H H H CI 1


.444 H CH20H H H F 1


.445 H CH20H H H Br 1


.446 H CH20H H H S02Me 1


.447 H CH20H H H SMe 1


.448 H CH20H H H S02NMe2 1


.449 H CH20H H H CF3 1


.450 H CH20H H H CH3 1


.451 H CH2OH H H CH{CH3)21


.452 H CH20H H H NOZ 1


.453 H CH20H H H OCH3 1


.454 H CH20H H H OCF2CF3 1



CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
- 63 -
Compel.R2 R, R3 R4 RS n


No.


.455 H CH20H H H CN 1


.456 H CHZOH H H CI 2


.457 H CH20H H H F 2


.458 H CHZOH H H Br 2


.459 H CH20H H H S02Me 2


.460 H CH20H H H SMe 2


.461 H CH20H H H S02NMe2 2


.462 H CH20H H H CF3 2


.463 H CH20H H H CH3 2


.464 H CHZOH H H CH(CH3)22


.465 H CH20H H H N02 2


.466 H CHZOH H H OCH3 2


.467 H CH20H H H OCF2CF3 2


.468 H CH20H H H CN 2


.469 H C02CH3 H H CI 0


.470 H C02CH3 H H F 0


.471 H C02CH3 H H Br 0


.472 H C02CH3 H H SOZMe 0


.473 H C02CH3 H H SMe 0


.474 H C02CH3 H H S02NMe2 0


.475 H COZCH3 H H CF3 0


.476 H C02CH3 H H CH3 0


.477 H C02CH3 H H CH(CH3)20


.478 H COZCH3 H H N02 0


.479 H C02CH3 H H OCH3 0


.480 H C02CH3 H H OCF2CF3 0


.481 H C02CH3 H H CN 0


.482 H C02CH3 H H CI 1


.483 H C02CH3 H H F 1


.484 H C02CH3 H H Br 1


.485 H C02CH3 H H S02Me 1



CA 02291101 1999-11-24
WO 99/09023 PCT/EP98I05247
-s4-
Compd.R2 R, R3 R4 R5 n


No.


.486 H C02CH3 H H SMe 1


.487 H C02CH3 H H S02NMe2 1


,488 H C02CH3 H H CF3 1


.489 H C02CH3 H H CH3 1


.490 H C02CH3 H H CH(CH3)2 1


.491 H C02CH3 H H N02 1


.492 H C02CH3 H H OCH3 1


.493 H COzCH3 H H OCF2CF3 1


.494 H C02CH3 H H CN 1


.495 H C02CH3 H H CI 2


.496 H C02CH3 H H F 2


.497 H C02CH3 H H Br 2


.498 H C02CH3 H H S02Me 2


.499 H C02CH3 H H SMe 2


.500 H C02CH3 H H S02NMe2 2


.501 H C02CH3 H H CF3 2


.502 H C02CH3 H H CH3 2


.503 H C02CH3 H H CH(CH3)2 2


.504 H C02CH3 H H NOZ 2


.505 H C02CH3 H H OCH3 2


.506 H C02CHs H H OCF2CF3 2


.507 H C02CH3 H H CN 2


.508 H CH=O H H CI 0


.509 H CH=O H H F 0


.510 H CH=O H H Br 0


.511 H CH=O H H S02Me 0


.512 H CH=O H H SMe 0


.513 H CH=O H H S02NMe2 0


.514 H CH=O H H CF3 0


.515 H CH=O H H CH3 0


.516 H CH=O H H CH(CH3)2 0



CA 02291101 1999-11-24
WO 99/09023 PCTIEP98/05247
-65-
Compd. RZ R, R3 R4 RS n


No.


.517 H CH=O H H N02 0


.518 H CH=O H H OCH3 0


.519 H CH=O H H OCF2CF3
0


.520 H CH=O H H CN 0


.521 H CH=O H H CI 1


.522 H CH=O H H F 1


.523 H CH~O H H Br 1


.524 H CH=O H H S02Me
1


.525 H CH=O H H SMe 1


.526 H CH=O H H S02NMe2
1


.527 H CH=O H H CF3 1


.528 H CH=O H H CH3 1


.529 H CH=O H H CH(CH3)2
1


.530 H CH=O H H NOZ 1


.531 H CH=O H H OCH3 1


.532 H CH=O H H OCF2CF3
1


.533 H CH=O H H CN 1


.534 H CH=O H H Cf 2


.535 H CH=O H H F 2


.536 H CH=O H H Br 2


.537 H CH=O H H S02Me
2


.538 H CH=O H H SMe 2


.539 H CH=O H H S02NMe2
2


.540 H CH=O H H CF3 2


.541 H CH=O H H CH3 2


.542 H CH=O H H CH(CH3}2
2


.543 H CH=O H H N02 2


.544 H CH=O H H OCH3 2


.545 H CH=O H H OCFZCF3
2


.546 H CH=O H H CN 2


.547 H CH=NOCH3 H H CI 0



CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
-66-
Compd. R2 R, R3 R4 RS n


No.


.548 H CH=NOCH3 H H F 0


.549 H CH=NOCH3 H H Br 0


.550 H CH=NOCH3 H H S02Me 0


.551 H CH=NOCH3 H H SMe 0


.552 H CH=NOCH3 H H S02NMe2
0


.553 H CH=NOCH3 H H CF3 0


.554 H CH=NOCH3 H H CH3 0


.555 H CH=NOCH3 H H CH(CH3)2
0


.556 H CH=NOCH3 H H N02 0


.557 H CH=NOCH3 H H OCH3 0


.558 H CH=NOCH3 H H OCF2CF3
0


.559 H CH=NOCH3 H H CN 0


.560 H CH=NOCH3 H H CI 1


.561 H CH=NOCH3 H H F 1


.562 H CH=NOCH3 H H Br 1


.563 H CH=NOCH3 H H S02Me 1


.564 H CH=NOCH3 H H SMe 1


.565 H CH=NOCH3 H H S02NMe2
1


.566 H CH=NOCH3 H H CF3 1


.567 H CH=NOCH3 H H CH3 1


.568 H CH=NOCH3 H H CH(CH3)2
7


.569 H CH=NOCHs H H N02 1


.570 H CH=NOCH3 H H OCH3 1


.571 H CH=NOCH3 H H OCF2CF3
1


.572 H CH=NOCH3 H H CN 1


.573 H CH=NOCH3 H H CI 2


.574 H CH=NOCH3 H H F 2


.575 H CH=NOCH3 H H Br 2


.576 H CH=NOCH3 H H S02Me 2


.577 H CH=NOCH3 H H SMe 2


.578 H CH=NOCH3 H H S02NMe2
2


*rB

CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
-67-
Compd.R2 R, R3 R4 R5 n


No.


.579 H CH=NOCH3 H H CF3 2


.580 H CH=NOCH3 H H CH3 2


.581 H CH=NOCH3 H H CH(CH3)22


.582 H CH=NOCH3 H H N02 2


.583 H CH=NOCH3 H H OCH3 2


.584 H CH=NOCH3 H H OCF2CF3 2


.585 H CH=NOCH3 H H CN 2


.586 H CH2NHz H H CI 0


.587 H CH2NH2 H H F 0


.588 H CH2NH2 H H Br 0


.589 H CH2NH2 H H S02Me 0


.590 H CHZNHZ H H SMe 0


.591 H CH2NH2 H H S02NMe2 0


.592 H CH2NH2 H H CF3 0


.593 H CH2NH2 H H CH3 0


.594 H CH2NH2 H H CH(CH3)20


.595 H CH2NH2 H H NOZ 0


.596 H CH2NH2 H H OCH3 0


.597 H CH2NH2 H H OCF2CF3 0


.598 H CH2NH2 H H CN 0


.599 H CH2NH2 H H CI 1


.600 H CH2NH2 H H F 1


.601 H CH2NHz H H Br 1


.602 H CH2NHz H H SOzMe 1


.603 H CHZNH2 H H SMe 1


.604 H CH2NH2 H H S02NMe2 1


.605 H CHZNH2 H H CF3 1


.606 H CH2NH2 H H CH3 1


.607 H CH2NH2 H H CH(CH3)21


.608 H CHzNH2 H H N02 1


.609 H CH2NH2 H H OCH3 1



CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
-68-
Compd. R2 R~ R3 R4 RS n


No.


.610 H CH2NH2 H H OCF2CF3
1


.611 H CH2NH2 H H CN 1


.612 H CHZNH2 H H CI 2


.613 H CH2NH2 H H F 2


.614 H CH2NH2 H H Br 2


.615 H CH2NH2 H H S02Me
2


.616 H CH2NH2 H H SMe 2


.617 H CH2NHz H H S02NMe2
2


.618 H CH2NH2 H H CF3 2


.619 H CH2NH2 H H CH3 2


.620 H CHZNH2 H H CH(CH3)2
2


.621 H CH2NH2 H H NOZ 2


.622 H CH2NH2 H H OCHs 2


.623 H CH2NH2 H H OCFZCF3
2


.624 H CH2NH2 H H CN 2


.625 H CN H H CI 0


.626 H CN H H F 0


.627 H CN H H Br 0


.628 H CN H H S02Me
0


.629 H CN H H SMe 0


.630 H CN H H S02NMe2
0


.631 H CN H H CF3 0


.632 H CN H H CH3 0


.633 H CN H H CH(CH3)2
0


.634 H CN H H N02 0


.635 H CN H H OCH3 0


.636 H CN H H OCF2CF3
0


.637 H CN H H CN 0


.638 H CN H H CI 1


.639 H CN H H F 1


.640 H CN H H Br 1



CA 02291101 1999-11-24
WO 99109023 PCT/EP98/05247
-ss-
Compd. RZ R, R3 R4 Rs n


No.


.641 H CN H H S02Me 7


.642 H CN H H SMe 1


.643 H CN H H S02NMe2
1


.644 H CN H H CF3 1


.645 H CN H H CH3 1


.646 H CN H H CH(CH3)2
1


.647 H CN H H N02 1


.648 H CN H H OCH3 1


.649 H CN H H OCF2CF3
1


.650 H CN H H CN 1


.651 H CN H H CI 2


.652 H CN H H F 2


.653 H CN H H Br 2


.654 H CN H H S02Me 2


.655 H CN H H SMe 2


.656 H CN H H S02NMe2
2


.657 H CN H H CF3 2


.658 H CN H H CH3 2


.659 H CN H H CH(CH3)2
2


.660 H CN H H NOZ 2


.661 H CN H H OCH3 2


.b62 H CN H H OCF2CF3
2


.663 H CN H H CN 2


.664 H CH(OH)CH3 H H CI 0


.665 H CH(OH)CH3 H H F 0


.666 H CH(OH)CH3 H H Br 0


.667 H CH{OH)CH3 H H S02Me 0


.568 H CH(OH)CH3 H H SMe 0


.669 H CH(OH)CH3 H H S02NMe2
0


.670 H CH(OH)CH3 H H CF3 0


.671 H CH(OH)CH3 H H CH3 0



CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
-70-
Compd.R2 R, R3 R4 RS n


No.


.672 H CH(OH)CH3 H H CH(CH3)2
0


.673 H CH(OH)CH3 H H NOZ 0


.674 H CH(OH)CH3 H H OCH3 0


.675 H CH(OH)CH3 H H OCF2CF3
0


.676 H CH(OH)CH3 H H CN 0


.677 H CH(OH)CH3 H H CI f


.678 H CH(OH)CH3 H H F 1


.679 H CH(OH)CH3 H H Br 1


.680 H CH(OH)CH3 H H S02Me 1


.681 H CH(OH)CH3 H H SMe 1


.682 H CH(OH)CH3 H H S02NMeZ
1


.683 H CH(OH)CH3 H H CF3 1


.684 H CH(OH)CH3 H H CH3 1


.685 H CH(OH)CH3 H H CH(CH3)2
1


.686 H CH(OH)CH3 H H NOZ 1


.687 H CH(OH)CH3 H H OCH3 1


.688 H CH(OH)CH3 H H OCF2CF3
f


.689 H CH(OH)CH3 H H CN 1


.690 H CH(OH)CH3 H H CI 2


.691 H CH(OH)CH3 H H F 2


.692 H CH(OH)CH3 H H Br 2


.693 H CH(OH)CH3 H H S02Me 2


.694 H CH(OH)CH3 H H SMe 2


.695 H CH(OH)CH3 H H S02NMe2
2


.696 H CH(OH)CH3 H H CF3 2


.697 H CH(OH)CH3 H H CH3 2


.698 H CH(OH)CH3 H H CH(CH3)2
2


.699 H CH(OH)CH3 H H N02 2


.700 H CH(OH)CH3 H H OCH3 2


.701 H CH(OH)CH3 H H OCF2CF3
2


.702 H CH(OH)CH3 H H CN 2


*rB

CA 02291101 1999-11-24
WO 99/09023 PCTIEP98/05247
_71
Compd.R2 R, R3 R4 R5 n


No.


.703 H CH=CHCH3 H H CI 0


.704 H CH=CHCH3 H H F 0


.705 H CH=CHCH3 H H Br 0


.706 H CH=CHCH3 H H S02Me 0


.707 H CH=CHCH3 H H SMe 0


.708 H CH=CHCH3 H H S02NMe2
0


.709 H CH=CHCH3 H H CF3 0


.710 H CH=CHCH3 H H CH3 0


.711 H CH=CHCH3 H H CH(CH3)2
0


.712 H CH=CHCH3 H H N02 0


.713 H CH=CHCH3 H H OCH3 0


.714 H CH=CHCH3 H H OCFZCF3
0


.715 H CH=CHCH3 H H CN 0


.716 H CH=CHCH3 H H CI 1


.717 H CH=CHCH3 H H F 1


.718 H CH=CHCH3 H H Br 1


.719 H CH=CHCH3 H H S02Me 1


.720 H CH=CHCH3 H H SMe 1


.721 H CH=CHCH3 H H S02NMe2
1


.722 H CH=CHCH3 H H CF3 1


.723 H CH=CHCH3 H H CH3 1


.724 H CH=CHCH3 H H CH(CH3)2
1


.725 H CH=CHCH3 H H N02 1


.726 H CH=CHCH3 H H OCH3 1


.727 H CH=CHCH3 H H OCFZCF3
1


.728 H CH=CHCH3 H H CN 1


.729 H CH=CHCH3 H H Ci 2


.?30 H CH=CHCH3 H H F 2


.731 H CH=CHCH3 H H Br 2


.732 H CH=CHCH3 H H S02Me 2


.733 H CH=CHCH3 H H SMe 2



CA 02291101 1999-11-24
WO 99/09023 _ 7~ _ PCTIEP98/05247
Compd. R2 R, R3 R4 R5 n


No.


.734 H CH=CHCH3 H H S02NMe2
2


.735 H CH=CHCH3 H H CF3 2


.736 H CH=CHCH3 H H CH3 2


.737 H CH=CHCH3 H H CH(CH3)2
2


.738 H CH=CHCH3 H H N02 2


.739 H CH=CHCH3 H H OCH3 2


.740 H CH=CHCH3 H H OCF2CF3
2


.741 H CH=CHCH3 H H CN 2


.742 H CH=CHC02CH3 H H CI 0


.743 H CH=CHC02CH3 H H F 0


.744 H CH=CHC02CH3 H H Br 0


.745 H CH=CHC02CH3 H H S02Me 0


.746 H CH=CHC02CH3 H H SMe 0


.747 H CH=CHC02CH3 H H SOZNMe2
0


.748 H CH=CHC02CH3 H H CF3 0


.749 H CH=CHC02CH3 H H CH3 0


.750 H CH=CHCOzCH3 H H CH(CH3)2
0


.751 H CH=CHC02CH3 H H NOZ 0


.752 H CH=CHC02CH3 H H OCH3 0


.753 H CH=CHC02CH3 H H OCF2CF3
0


.754 H CH=CHC02CH3 H H CN 0


.755 H CH=CHC02CH3 H H CI 1


.756 H CH=CHC02CH3 H H F 1


.757 H CH=CHC02CH3 H H Br 1


.758 H CH=CHC02CH3 H H S02Me 1


.759 H CH=CHC02CH3 H H SMe 1


.760 H CH=CHC02CH3 H H S02NMe2
1


.761 H CH=CHC02CH3 H H CF3 1


.762 H CH=CHC02CH3 H H CH3 1


.763 H CH=CHC02CH3 H H CH(CH3)2


.764 H CH=CHC02CH3 H H N02 1



CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
- 73 -
Compel.Rz R, R3 R4 Rs n


No.


.765 H CH=CHC02CH3 H H OCH3 1


.766 H CH=CHC02CH3 H H OCF2CF3
1


.767 H CH=CHC02CH3 H H CN 1


.768 H CH=CHC02CH3 H H CJ 2


.769 H CH=CHC02CH3 H H F 2


.770 H CH=CHC02CH3 H H Br 2


.771 H CH=CHC02CH3 H H S02Me 2


.772 H CH=CHC02CH3 H H SMe 2


.773 H CH=CHCOZCH3 H H S02NMe2
2


.774 H CH=CHC02CH3 H H CF3 2


.775 H CH=CHC02CH3 H H CH3 2


.776 H CH=CHC02CH3 H H CH(CH3)2
2


.777 H CH=CHCOZCH3 H H N02 2


.778 H CH=CHC02CH3 H H OCH3 2


.779 H CH=CHC02CH3 H H OCF2CF3
2


.780 H CH=CHC02CH3 H H CN 2


.781 CH3 CH3 H H CI 0


.782 CH3 CH3 H H F 0


.783 CH3 CH3 H H Br 0


.784 CH3 CH3 H H SOZMe 0


.785 CH3 CH3 H H SMe 0


.786 CH3 CH3 H H S02NMez
0


.787 CH3 CH3 H H CF3 0


.788 CH3 CHs H H CH3 0


.789 CH3 CH3 H H CH(CH3)2
0


.790 CH3 CH3 H H N02 0


.791 CH3 CH3 H H OCH3 0


.792 CH3 CH3 H H OCF2CF3
0


.793 CH3 CH3 H H CN 0


.794 CH3 CH3 H H CI 1


.795 CH3 CH3 H H F 1



CA 02291101 1999-11-24
WO 99/09023 _ 74 _ PCT/EP98/05247
Compd.R2 R, R3 R4 RS n


No.


.796 CH3 CH3 H H Br 1


.797 CH3 CH3 H H S02Me 1


.798 CH3 CH3 H H SMe 1


.799 CH3 CH3 H H S02NMe2
1


.800 CH3 CH3 H H CF3 1


.801 CH3 CH3 H H CH3 1


.802 CH3 CH3 H H CH(CH3)2
1


.803 CH3 CH3 H H N02 1


.804 CH3 CH3 H H OCH3 1


.805 CH3 CH3 H H OCF2CF3
1


.806 CH3 CH3 H H CN 1


.807 CH3 CH3 H H CI 2


.808 CH3 CH3 H H F 2


.809 CH3 CH3 H H Br 2


.810 CH3 CH3 H H S02Me 2


.811 CH3 CH3 H H SMe 2


.812 CH3 CH3 H H S02NMe2
2


.813 CH3 CH3 H H CF3 2


.814 CH3 CH3 H H CH3 2


.815 CH3 CH3 H H CH(CH3)2
2


.816 CH3 CH3 H H N02 2


.817 CH3 CH3 H H OCH3 2


.818 CH3 CH3 H H OCF2CFs
2


.819 CH3 CH3 H H CN 2



CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
-75-
Table 7: Compounds of formula II
R, CH3


RZ S(O)~ O S(O)~=


Rs i w N (II)


R ~
4 /


\ O


Rs


Compd. R2 R, R3 R4 R5 n n2 Phys. data


No.


7.001 H CH3 H H CI 0 0


7.002 H CH3 H H F 0 0


7.003 H CH3 H H Br 0 0


7.004 H CH3 H H SOzMe 0 0


7.005 H CH3 H H SMe 0 0


7.006 H CH3 H H S02NMe2 0 0


7.007 H CH3 H H CF3 0 0


7.008 H CH3 H H CH3 0 0


7.009 H CH3 H H CH(CH3)20 0


7.010 H CH3 H H NOZ 0 0


7.OI1 H CH3 H H OCH3 0 0


7.012 H CH3 H H OCF2CF3 0 0


7.013 H CH3 H H CN 0 0


7.014 H CH3 H H CI 1 0


7.015 H CH3 H H F 1 0


7.016 H CH3 H H Br 1 0


7.017 H CH3 H H S02Me 1 0


7.018 H CH3 H H SMe 1 0


7.019 H CH3 H H SOZNMe2 1 0


7.020 H CH3 H H CF3 1 0


7.021 H CH3 H H CH3 1 0


7.022 H CH3 H H CH(CH3)21 0


7.023 H CH3 H H N02 1 0


7.024 H CH3 H H OCH3 1 0


7.025 H CH3 H H OCF2CF3 1 0




CA 02291101 1999-11-24
WO 99109023 PCT/EP98/05247
-76-
Compd.RZ R, R3 R4 RS n n2 Phys.
data


No.


7.026 H CH3 H H CN 1 0


7.027 H CH3 H H CI 2 0 129-130C
'


7.028 H CH3 H H F 2 0


7.029 H CHs H H Br 2 0


7.030 H CH3 H H S02Me 2 0


7.031 H CH3 H H SMe 2 0


7.032 H CH3 H H S02NMe2 2 0


7.033 H CH3 H H CF3 2 0


7.034 H CH3 H H CH3 2 0


7.035 H CH3 H H CH(CH3)22 0


7.036 H CH3 H H N02 2 0


7.037 H CH3 H H OCH3 2 0


7.038 H CH3 H H OCF2CF3 2 0


7.039 H CH3 H H CN 2 0


7.040 H CH3 H H CI 0 0


7.041 H CH3 H H F 0 0


7.042 H CH3 H H Br 0 0


7.043 H CH3 H H S02Me 0 0


7.044 H CH3 H H SMe 0 0


7.045 H CH3 H H S02NMe2 0 0


7.046 H CH3 H H CF3 0 0


7.047 H CH3 H H CH3 0 0


7.048 H CH3 H H CH(CH3)20 0


?.049 H CH3 H H N02 0 0


7.050 H CH3 H H OCH3 0 0


7.051 H CH3 H H OCF2CF3 0 0


7.052 H CH3 H H CN 0 0


7.053 H CH3 H H CI 1 0


7.054 H CH3 H H F 1 0


7.055 H CH3 H H Br 1 0


7.056 H CH3 H H S02Me 1 0


7.057 H CH3 H H SMe 1 0



CA 02291101 1999-11-24
WO 99109023 PCTIEP98I05247
_77_
Compd.R2 R1 RsR4 R5 n n2 Phys.
data


No.


7.058 H CH3 H H S02NMex 1 0


7.059 H CHa H H CF3 1 0


7.060 H CH3 H H CH3 1 0


7.061 H CH3 H H CH(CH3)z1 0


7.062 H CH3 H H N02 1 0


7.063 H CH3 H H OCH3 1 0


7.064 H CH3 H H OCFZCF3 1 0


7.065 H CH3 H H CN 1 0


7.066 H CH3 H H CI 2 0


7.067 H CH3 H H F 2 0


7.068 H CH3 H H Br 2 0


7.069 H CH3 H H S02Me 2 0


7.070 H CH3 H H SMe 2 0


7.071 H CH3 H H S02NMe2 2 0


7.072 H CH3 H H CF3 2 0


7.073 H CH3 H H CH3 2 0


7.074 H CH3 H H CH(CH3)22 0


7.075 H CH3 H H N02 2 0


7.076 H CH3 H H OCH3 2 0


7.077 H CH3 H H OCFzCF3 2 0


7.078 H CH3 H H CN 2 0


7.079 H CH3 H H CI 0 1


7.080 H CH3 H H F 0 1


7.081 H CH3 H H Br 0 1


7.082 H CH3 H H S02Me 0 1


7.083 H CH3 H H SMe 0 1


7.084 H CH3 H H S02NMe2 0 1


7.085 H CH3 H H CF3 0 1


7.086 H CH3 H H CH3 0 1


7.087 H CH3 H H CH(CH3)z0 1


7.088 H CH3 H H NOZ 0 1


7.089 H CH3 H H OCH3 0 1




CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
_7g_
Compd. R2 R, R3 R4 Rs n n2 Phys.
data


No.


7.090 H CHs H H OCF2CF3 0 1


7.091 H CH3 H H CN 0 1


7.092 H CH3 H H CI 1 1


7.093 H CH3 H H F 1 1


7.094 H CH3 H H Br 1 1


7.095 H CH3 H H S02Me 1 1


7.096 H CHs H H SMe 1 1


7.097 H CH3 H H S02NMe2 1 1


7.098 H CH3 H H CF3 1 1


7.099 H CH3 H H CH3 1 1


7.100 H CH3 H H CH(CH3)21 1


7.101 H CH3 H H NOZ 1 1


7.102 H CH3 H H OCH3 1 1


7.103 H CH3 H H OCF2CF3 1 1


7.104 H CH3 H H CN 1 1


7.105 H CH3 H H CI 2 1


7.106 H CH3 H H F 2 1


7.107 H CH3 H H Br 2 1


7.108 H CH3 H H S02Me 2 1


7.109 H CH3 H H SMe 2 1


7.110 H CH3 H H S02NMez 2 1


7.111 H CH3 H H CF3 2 1


7.112 H CH3 H H CH3 2 1


7.113 H CH3 H H CH(CH3?22 1


7.114 H CH3 H H N02 2 1


7.115 H CH3 H H OCH3 2 1


7.116 H CH3 H H OCF2CF3 2 1


7.117 H CH3 H H CN 2 1


7.118 H CH3 H H CI 0 2


7.119 H CH3 H H F 0 2


7.120 H CH3 H H Br 0 2


7.121 H CHs H H S02Me 0 2




CA 02291101 1999-11-24
WO 99109023 PCT/EP98/05247
-79-
Compel.R2 R, R3 R4 R5 n nz Phys.
data


No.


7.122 H CH3 H H SMe 0 2


7.123 H CH3 H H S02NMez 0 2


7.124 H CH3 H H CF3 0 2


7.125 H CH3 H H CH3 0 2


7.126 H CH3 H H CH(CH3)20 2


7.127 H CH3 H H NOz 0 2


7.128 H CH3 H H OCH3 0 2


7.129 H CH3 H H OCFZCF3 0 2


7.130 H CHs H H CN 0 2


7.131 H CH3 H H CI 1 2


7.132 H CH3 H H F 1 2


7.133 H CH3 H H Br 1 2


7.134 H CH3 H H S02Me 1 2


7.135 H CH3 H H SMe 1 2


7.136 H CH3 H H S02NMez 1 2


7.137 H CH3 H H CF3 1 2


7.138 H CH3 H H CH3 1 2


7.139 H CH3 H H CH(CH3)z1 2


7.140 H CH3 H H NOz 1 2


7.141 H CH3 H H OCH3 1 2


7.142 H CH3 H H OCF2CF3 1 2


7.143 H CH3 H H CN 1 2


7.144 H CH3 H H CI 2 2


7.145 H CH3 H H F 2 2


7.146 H CH3 H H Br 2 2


7.147 H CH3 H H S02Me 2 2


7.148 H CH3 H H SMe 2 2


7.149 H CH3 H H S02NMez 2 2


7.150 H CH3 H H CF3 2 2


7.151 H CH3 H H CH3 2 2


7.152 H CH3 H H CH(CH3)z2 2


7.153 H CH3 H H NOz 2 2




CA 02291101 1999-11-24
WO 99/09023 PCT/EP98105247


-80-


Compd. R2 R, R3R4 Rs n n2 Phys. data


No.


7.154 H CH3 H H OCH3 2 2


7.155 H CH3 H H OCF2CF3 2 2


7.156 H CHs H H CN 2 2


?.157 CH3 CH3 H H CI 0 0


7.158 CH3 CH3 H H F 0 0


7.159 CH3 CH3 H H Br 0 0


7.160 CH3 CH3 H H S02Me 0 0


7.161 CH3 CH3 H H SMe 0 0


7.162 CH3 CH3 H H S02NMe2 0 0


7.163 CH3 CH3 H H CF3 0 0


7.164 CH3 CH3 H H CHs 0 0


7.165 CH3 CH3 H H CH(CH3)20 0


7.166 CH3 CH3 H H NOZ 0 0


7.167 CH3 CH3 H H OCH3 0 0


7.168 CH3 CH3 H H OCF2CF3 0 0


7.169 CH3 CH3 H H CN 0 0


7.170 CH3 CH3 H H CI 1 0


7.171 CH3 CH3 H H F 1 0


7.172 CH3 CH3 H H Br 1 0


7.173 CH3 CH3 H H S02Me 1 0


7.174 CH3 CH3 H H SMe 1 0


7.175 CH3 CH3 H H S02NMe2 1 0


7.176 CH3 CH3 H H CF3 1 0


7.177 CH3 CH3 H H CH3 1 0


7.178 CH3 CH3 H H CH(CH3)21 0


7.179 CH3 CH3 H H N02 1 0


7.180 CH3 CH3 H H OCH3 1 0


7.181 CH3 CH3 H H OCF2CF3 1 0


7.182 CH3 CH3 H H CN 1 0


7.183 CH3 CH3 H H CI 2 0


7.184 CH3 CH3 H H F 2 0


7.185 CH3 CH3 H H Br 2 0



CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247


-81 -


Compel. R2 R, R3 R4 RS n n2 Phys. data


No.


7.186 CH3 CH3 H H S02Me 2 0


7.187 CH3 CHs H H SMe 2 0


7.188 CH3 CH3 H H S02NMe2 2 0


7.189 CH3 CH3 H H CF3 2 0


7.190 CH3 CH3 H H CH3 2 0


7.191 CHs CHa H H CH(CH3)22 0


7.192 CH3 CH3 H H N02 2 0


7.193 CH3 CH3 H H OCH3 2 0


7.194 CH3 CH3 H H OCF2CF3 2 0


7.195 CH3 CH3 H H CN 2 0


Table 8: A further group of compounds of formula I corresponds to general
formula Im
CH3
O
R2 S(O) n O O
R3 ~ ~ {Im), wherein the meanings of the corresponding
R4 1 N
\ ~ O
R5
substituents R, to RS and n are given in Table B, so that 78 specific
compounds of formula
Im are disclosed.
Table 9: A further group of compounds of formula ! corresponds to general
formula In
S(O) ~ O
3 R ~ ~ (In), wherein the meanings of the corresponding substituents
N
4
\ O
RS
R, to R5 and n are given in Table B, so that 78 specific compounds of formula
In are
disclosed.


CA 02291101 1999-11-24
WO 99/09023 PCTlEP98105247
-82-
Table 10: A further group of compounds of formula i corresponds to general
formula to
R~
S(p) ~ O CH3
R3 ~ w N (lo), wherein the meanings of the corresponding
R4
N\
R5 OH CH3
substituents R, to R5 and n are given in Table B, so that 78 specific
compounds of formula
to are disclosed.
Table 11: A further group of compounds of formula I corresponds to general
formula Ip
RZ S(O)~ o
R3 ~ ~ N (Ip), wherein the meanings of the corresponding
R4 w ( ~ N
R5 OH
Cr2H5
substituents R, to R5 and n are given in Table B, so that 78 specific
compounds of formula
ip are disclosed.
Table B
Campd.R2 R, R3 R4 R5 n


No.


.001 H CH3 H H CI 0


.002 H CH3 H H F 0


.003 H CH3 H H Br 0


.004 H CH3 H H S02Me 0


.005 H CH3 H H SMe 0


.006 H CH3 H H S02NMe2
0


.007 H CH3 H H CF3 0


.008 H CH3 H H CH3 0


.009 H CH3 H H CH(CH3)2
0


.010 H CH3 H H N02 0


.011 H CH3 H H OCH3 0


.012 H CH3 H H OCF2CF3
0




CA 02291101 1999-11-24
WO 99/09023 - $3 - PCT/EP98105247
Compd.RZ R, R3 R4 RS n


No.


.013 H CH3 H H CN 0


.014 H CH3 H H CI 1


.015 H CH3 H H F 1


.016 H CH3 H H Br 1


.017 H CH3 H H S02Me 1


.018 H CH3 H H SMe 1


.019 H CH3 H H SO2NMe2 1


.020 H CH3 H H CF3 1


.021 H CH3 H H CH3 1


.022 H CH3 H H CH(CH3)21


.023 H CH3 H H N02 1


.024 H CH3 H H OCH3 1


.025 H CH3 H H OCF2CF3 1


.026 H CH3 H H CN 1


.027 H CH3 H H C! 2


.028 H CH3 H H F 2


.029 H CH3 H H Br 2


.030 H CH3 H H S02Me 2


.031 H CH3 H H SMe 2


.032 H CH3 H H S02NMe2 2


.033 H CH3 H H CF3 2


.034 H CH3 H H CH3 2


.035 H CH3 H H CH(CH3)22


.036 H CH3 H H N02 2


.037 H CH3 H H OCH3 2


.038 H CH3 H H OCF2CF3 2


.039 H CH3 H H CN 2


.040 CH3 CH3 H H CI 0


.041 CH3 CH3 H H F 0


.042 CH3 CH3 H H Br 0


.043 CH3 CH3 H H S02Me 0


.044 CH3 CH3 H H SMe 0




CA 02291101 1999-11-24
WO 99/09023 PCT/EP98I05247
-84-
Compd.R2 R, R3 R4 RS n


No.


.045 CH3 CH3 H H S02NMe20


.046 CH3 CH3 H H CF3 0


.047 CH3 CH3 H H CH3 0


.048 CH3 CH3 H H CH(CH3)20


.049 CH3 CH3 H H N02 0


.050 CH3 CH3 H H OCH3 0


.051 CH3 CH3 H H OCF2CF30


.052 CH3 CH3 H H CN 0


.053 CH3 CH3 H H CI 1


.054 CH3 CH3 H H F 1


.055 CH3 CH3 H H Br 1


.056 CH3 CH3 H H S02Me 1


.057 CH3 CH3 H H SMe 1


.058 CH3 CH3 H H S02NMe21


.059 CH3 CH3 H H CF3 1


.060 CH3 CH3 H H CH3 1


.061 CH3 CH3 H H CH(CH3)Z1


.062 CH3 CH3 H H N02 1


.063 CH3 CH3 H H OCH3 1


.064 CH3 CH3 H H OCF2CF31


.065 CH3 CH3 H H CN 1


.066 CH3 CH3 H H CI 2


.067 CH3 CH3 H H F 2


.068 CH3 CH3 H H Br 2


.069 GH3 CH3 H H S02Me 2


.070 CH3 CH3 H H SMe 2


.071 CH3 CH3 H H S02NMe22


.072 CH3 CH3 H H CF3 2


.073 CH3 CH3 H H CH3 2


.074 CH3 CH3 H H CH(CH3)22


.075 CH3 CH3 H H N02 2


.076 CH3 CH3 H H OCH3 2



CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
-85-
Compd. R2 R, R3 R4 R$ n
No.
.077 CH3 CH3 H H OCF2CF3 2
.078 CH3 CH3 H H CN 2
Table 12: Compounds of formula Iq
Rs
(Iq)
R is
~ n s
Compd.R6 (C3) R, Rs (C5) Rye n Phys. data


No.


12.001CH3 CH3 H H 0


12.002CH3 CH3 CH3 H 0


12.003CH3 CH3 CH=CHZ H 0


12.004CH3 CH3 Br H 0


12.005CH3 CH3 SMe H 0


12.006CH3 CH3 H H 1


12.007CH3 CH3 CH3 H 1


12.008CH3 CH3 CH=CH2 H 1


12.009CH3 CH3 Br H 1


12.01 CH3 CH3 SMe H 1


12.011CH3 CH3 H H 2 159-161 C


12.012CH3 CH3 CH3 H 2 157-159C


12.013CH3 CH3 CH=CH2 H 2


12.014CH3 CH3 Br H 2


12.015CH3 CH3 SMe H 2


12.016CH3 CH3 CH3 CH3 0


12.017CH3 CH3 CH=CHZ CH3 0


i 2.018CH3 CH3 Br CH3 0



CA 02291101 1999-11-24
W O 99/09023 PCTIEP98/05247
-86-
Compd. Rs (Cs)R, RB (C5) R,e n Phys. data


No.


12.019 CH3 CH3 SMe CH3 0


12.02 CH3 CH3 H CH3 1


12.021 CH3 CH3 CH3 CH3 1


12.022 CH3 CH3 CH=CHZ CH3 1


12.023 CH3 CH3 Br CH3 1


12.024 CH3 CH3 SMe CH3 1


12.025 CH3 CH3 H CH3 2


12.026 CH3 CH3 CHs CH3 2


12.027 CH3 CH3 CH=CH2 CH3 2


12.028 CH3 CH3 Br CH3 2


12.029 CH3 CH3 SMe CH3 2


'R6 (C3)' ubstituent
in Table RB
12 above is
means bonded
that to
the carbon
s atom
3
in
the


compound
of formula
Iq;
and
accordingly
'RB
(C5)'
means
that
the
substituent
R6 is
bonded


to carbon
atom
in
the
compound
of formula
iq.


Table of formula Ir
13:
Compounds


(Ir)


ie


Compd. R6 R6 R, R, R,e n Phys. data


No.


13.001 H H H H CH3 0 viscous oii


13.002 H H H H CF3 0


13.003 H H H H C02CHZCH3 0 viscous oil


13.004 H H H H CH3 1


13.005 H H H H CF3 1


13.006 H H H H C02CH2CH3 1



CA 02291101 1999-11-24
WO 99/09023 PCTIEP98/05247
_87_
Compd. R6 R6 R, R, R,e n Phys. data


No.


13.007 H H H H CH3 2 129-132C


13.008 H H H H CF3 2


13.009 H H H H C02CH2CH3 2 viscous
oii


13.010 CH3 H H H H 0


13.011 CH3 H H H CH3 0


13.012 CH3 H H H CF3 0


.13.013CH3 H H H COZCH2CH3 0


13.014 CH3 H H H H 1


13.015 CH3 H H H CH3 1


13.016 CH3 H H H CF3 1


13.017 CH3 H H H C02CH2CH3 1


13.018 CH3 H H H H 2


13.019 CH3 H H H CH3 2


13.020 CH3 H H H CF3 2


13.021 CH3 H H H C02CH2CHs 2


13.022 CH3 H CH3 H H 0 139-140C


13.023 CH3 H CH3 H CH3 0


13.024 CH3 H CH3 H CF3 0


13.025 CH3 H CH3 H C02CH2CH3 0


13.02fiCH3 H CH3 H H 1


13.027 CH3 H CH3 H CH3 1


13.028 CH3 H CH3 H CF3 1


13.029 CH3 H CH3 H C02CH2CH3 1


13.030 CH3 H CH3 H H 2 179-180C


13.031 CH3 H CH3 H CH3 2


13.032 CH3 H CH3 H CF3 2


13.033 CH3 H CH3 H C02CH2CH3 2


13.034 CH3 CH3 CH3 H H 0 viscous
oil


13.035 CH3 CH3 CH3 H CH3 0


13.036 CH3 CH3 CH3 H CF3 0


13.037 CH3 CH3 CH3 H C02CH2CH3 0


13.038 CH3 CH3 CH3 H H 1 amorphous



CA 02291101 1999-11-24
WO 99/09023 PCTIEP98/05247
-88-
Compel.R6 Rs R~ R~ R,e n Phys. data


No.


13.039CH3 CH3 CH3 H CH3 1


13.040CH3 CH3 CH3 H CF3 1


13.041CH3 CH3 CH3 H C02CHZCH3 1


13.042CH3 CH3 CH3 H H 2 resin


13.043CH3 CH3 CH3 H CH3 2


13.044CH3 CH3 CH3 H CF3 2


13.045CH3 CH3 CH3 H C02CH2CH3 2


13.046CH3 CH3 CH3 CH3 H 0


13.047CH3 CH3 CH3 CH3 CH3 0


13.048CH3 CH3 CH3 CH3 CF3 0


13.049CH3 CH3 CH3 CH3 C02CH2CH3 0


13.050CH3 CH3 CH3 CH3 H 1


13.051CH3 CH3 CH3 CH3 CH3 1


13.052CH3 CH3 CH3 CH3 CF3 1


13.053CH3 CH3 CH3 CH3 C02CH2CH3 1


13.054CH3 CH3 CH3 CH3 H 2


13.055CH3 CH3 CH3 CH3 CH3 2


13.056CH3 CH3 CH3 CH3 CF3 2


13.057CH3 CH3 CH3 CH3 C02CH2CH3 2


13.058SCH3 H CH3 H : H 0 125-128C


13.059S02CH3 H CH3 H H 0 viscous oil


13.060SCH3 H CH3 H CH3 0


13.061SCH3 H CH3 H CF3 0


13.062SCH3 H CH3 H C02CH2H3 0


13.063SCH3 H CH3 H H 1


13.064SCH3 H CH3 H CH3 1


13.065SCH3 H CH3 H CF3 1


13.066SCH3 H CH3 H C02CH2CH3 1


13.067SCH3 H CH3 H H 2


i 3.068SCH3 H CH3 H CH3 2


13.069SCH3 H CH3 H CF3 2


13.070SCH3 H CH3 H C02CH2CH3 2



CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
-89-
Compd.R6 R6 R, R, R,e n Phys. data


No.


13.071SCH3 CH3 CH3 H H 0 111-113C


13.072SCH3 CH3 CH3 H CH3 0


13.073SCH3 CH3 CH3 H CF3 0


13.074SCH3 CH3 CH3 H C02CH2CH3 0


13.075SCH3 CH3 CH3 H H 1


13.076SCH3 CH3 CH3 H CH3 1


13.077SCH3 CH3 CH3 H CF3 1


13.078SCH3 CH3 CH3 H C02CH2CH3 1


13.079SCH3 CH3 CH3 H H 2 resin


13.080S02CH3CH3 CH3 H H 2 244-246C


13.081SCH3 CH3 CH3 H CH3 2


13.082SCH3 CH3 CH3 H CF3 2 viscous oil (E
isomer)


13.083SCH3 CH3 CH3 H CF3 2 viscous oil (Z
isomer)


13.084SCH3 CH3 CH3 H C02CH2CH3 2


13.085SCH3 H CH3 CH3 H 0


13.086SCH3 H CH3 CH3 CH3 0


13.087SCH3 H CH3 CH3 CF3 0


13.088SCH3 H CH3 CH3 C02CH2CH3 0


13.089SCH3 H CH3 CH3 H 1


13.090SCH3 H CH3 CH3 CH3 1


13.091SCH3 H CH3 CH3 CF3 1


13.092SCH3 H CH3 CH3 C02CH2CH3 1


13.093SCH3 H CH3 CH3 H 2


13.094SCH3 H CH3 CH3 CH3 2


13.095SCH3 H CH3 CH3 CF3 2


i 3.096SCH3 H CH3 CH3 C02CH2CH3 2


13.097SCH3 CH3 CH3 CH3 H 0


13.098SCH3 CH3 CH3 CH3 CH3 0


13.099SCH3 CH3 CH3 CH3 CF3 0


13.100SCH3 CH3 CH3 CH3 C02CH2CH3 0


13.101SCH3 CH3 CH3 CH3 H 1


13.102SCH3 CH3 CH3 CH3 CH3 1



CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
-90-
Compd.R6 R6 R, R~ R,e n Phys. data


No.


13.103SCH3 CH3 CH3 CH3 CF3 1


13.104SCH3 CH3 CH3 CH3 C02CH2CH3 1


13.105SCH3 CHI CH3 CH3 H 2


13.106SCH3 CH3 CH3 CH3 CH3 2


13.107SCH3 CH3 CH3 CH3 CF3 2


13.108SCH3 CH3 CH3 CH3 C02CH2CH3 2


13.109SCH3 SCH3 H H H 0


13.110SCH3 SCH3 H H CH3 0


13.111SCH3 SCH3 H H CF3 0


13.112SCH3 SCH3 H H C02CH2CH3 0


i 3.113SCH3 SCH3 H H H 1


13.114SCH3 SCH3 H H CH3 1


13.115SCH3 SCH3 H H CF3 1


13.116SCH3 SCH3 H H C02CH2CH3 1


13.117SCH3 SCH3 H H H 2


13.118SCH3 SCH3 H H CH3 2


13.119SCH3 SCH3 H H CF3 2


13.120SCH3 SCH3 H H COZCH2CH3 2


13.121SCH3 SCH3 CH3 CH3 H 0


13.122SCH3 SCH3 CH3 CH3 CH3 0


13.123SCH3 SCH3 CH3 CH3 CF3 0


13.124SCH3 SCH3 CH3 CH3 C02CH2CHa 0


13.125SCH3 SCH3 CH3 CH3 H 1


13.126SCH3 SCH3 CH3 CH3 CH3 1


13.127SCH3 SCH3 CH3 CH3 CF3 1


13.128SCH3 SCH3 CH3 CH3 C02CH2CH3 1


13.129SCH3 SCH3 CH3 CH3 H 2 128-130C (meso
form)


13.130SCH3 SCH3 CH3 CH3 H 2 i 89-192C (E isomer)


13.131SCH3 SCH3 CH3 CH3 CH3 2


13.132SCH3 SCH3 CH3 CH3 CF3 2


13.133SCH3 SCH3 CH3 CH3 C02CH2CH3 2


13.134OCH3 H H H H 0



CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
-91 -
Compd.Rs Rs R~ R, Rie n Phys. data


No.


13.135OCH3 H H H CH3 0


13.136OCH3 H H H CF3 0


13.137OCH3 H H H C02CH2CH3 0


13.138OCH3 H H H H 1


13.139OCH3 H H H CH3 1


13.140OCH3 H H H CF3 1


13.141OCH3 H H H C02CH2CH3 1


13.142OCH3 H H H H 2


13.143OCH3 H H H CH3 2


13.144OCH3 H H H CF3 2


13.145OCH3 H H H C02CH2CH3 2


13.146OCH3 H CH3 H H 0


13.147OCH3 H CH3 H CH3 0


13.148OCH3 H CH3 H CF3 0


13.149OCH3 H CH3 H C02CH2CH3 0


13.150OCH3 H CH3 H H 1


13.151OCH3 H CH3 H CH3 1


13.152OCH3 H CH3 H CF3 1


13.153OCH3 H CH3 H C02CH2CH3 1


13.154OCH3 H CH3 H H 2


13.155OCH3 H CH3 H CH3 2


13.156OCH3 H CH3 H CF3 2


13.157OCH3 H CH3 H C02CHZCH3 2


13.158OCH3 CH3 CH3 H H 0 resin {E isomer)


13.159OCH3 CH3 CH3 H H 0 104-105C (Z isomer)


13.160OCH3 CH3 CH3 H CH3 0


13.161OCH3 CH3 CH3 H CF3 0


13.162OCH3 CH3 CH3 H C02CH2CH3 0


13.163OCH3 CH3 CH3 H H 1


i 3.164OCH3 CH3 CH3 H CH3 1


13.165OCH3 CH3 CH3 H CF3 1


13.166OCH3 CH3 CH3 H C02CHZCH3 1


*rB

CA 02291101 1999-11-24
WO 99/09023 _ 92 _ PCT/EP98/05247
Compd.Rs R6 R, R, R,e n Phys. data


No.


13.167OCH3 CH3 CH3 H H 2 resin (Z isomer)


13.168OCH3 CH3 CH3 H H 2 resin (E isomer)


13.169OCH3 CH3 CH3 H CH3 2


13.170OCH3 CH3 CH3 H CF3 2


13.171OCH3 CH3 CH3 H C02CH2CH3 2


13.172OCH3 CH3 CH3 CH3 H 0


13.173OCH3 CH3 CH3 CH3 CH3 0


13.174OCH3 CH3 CH3 CH3 CF3 0


13.175OCH3 CH3 CH3 CH3 COZCH2CH3 0


13.176OCH3 CH3 CH3 CH3 H 1


13.177OCH3 CH3 CH3 CH3 CH3 1


13.178OCH3 CH3 CH3 CH3 CF3 1


13.179OCH3 CH3 CH3 CH3 C02CHZCH3 1


13.180OCH3 CH3 CH3 CH3 H 2


13.181OCH3 CH3 CH3 CH3 CH3 2


13.182OCH3 CH3 CH3 CH3 CF3 2


13.183OCH3 CH3 CH3 CH3 C02CH2CH3 2


13.184OCH3 H OCH3 H H 0


13.185OCH3 H OCH3 H CH3 0


13.186OCH3 H OCH3 H CF3 0


13.187OCH3 H OCH3 H C02CH2CH3 0


13.188OCH3 H OCH3 H H 1


13.189OCH3 H OCH3 H CH3 1


13.190OCH3 H OCH3 H CF3 1


13.191OCH3 H OCH3 H C02CH2CH3 1


13.192OCH3 H OCH3 H H 2


13.193OCH3 H OCH3 H CH3 2


13.194OCH3 H OCH3 H CF3 2


13.195OCH3 H OCH3 H C02CH2CH3 2


13.196OCH3 CH3 OCH3 CH3 H 0


13.197OCH3 CH3 OCH3 CH3 CH3 0


13.198OCH3 CH3 OCH3 CH3 CF3 0



CA 02291101 1999-11-24
WO 99109023 PCT/EP98/05247
-93-
Compd. Rs Rs R, R~ R,s n Phys. data


No.


13.199 OCH3 CH3 OCH3 CH3 C02CH2CH3 0


13.200 OCH3 CH3 OCH3 CH3 H 1


13.201 OCH3 CH3 OCH3 CH3 CH3 1


13.202 OCH3 CH3 OCH3 CH3 CF3 1


13.203 OCH3 CH3 OCH3 CH3 C02CH2CH3 1


13.204 OCH3 CH3 OCH3 CH3 H 2


i 3.205OCH3 CH3 OCH3 CH3 CH3 2


13.206 OCH3 CH3 OCH3 CH3 CF3 2


13.207 OCH3 CH3 OCH3 CH3 C02CHZCH3 2


13.208 SCH3 CH3 OCH3 H H 0 amorphous


13.209 SCH3 CH3 OCH3 H ~ CH3 0


13.210 SCH3 CH3 OCH3 H CF3 0


13.211 SCH3 CH3 OCH3 H C02CHzCH3 0


13.212 SCH3 CH3 OCH3 H H 1


13.213 SCH3 CH3 OCH3 H CH3 1


13.214 SCH3 CH3 OCH3 H CF3 1


13.215 SCH3 CH3 OCH3 H COZCHZCH3 1


13.216 SCH3 CH3 OCH3 H H 2 166-168C


13.217 SCH3 CH3 OCH3 H CH3 2


13.218 SCH3 CH3 OCH3 H CF3 2


13.219 SCH3 CH3 OCH3 H C02CH2CH3 2


13.220 SCH3 CH3 OCH3 CH3 H 0


13.221 SCH3 CH3 OCH3 CH3 CH3 0


13.222 SCH3 CH3 OCH3 CH3 CF3 0


13.223 SCH3 CH3 OCH3 CH3 COZCH2CH3 0


13.224 SCH3 CH3 OCH3 CH3 H 1


13.225 SCH3 CH3 OCH3 CH3 CH3 1


13.226 SCH3 CH3 OCH3 CH3 CF3 1


13.227 SCH3 CH3 OCHs CH3 C02CH2CH3 1


13.228 SCH3 CH3 OCH3 CH3 H 2


13.229 SCH3 CH3 OCH3 CH3 CH3 2


13.230 SCH3 CH3 OCH3 CH3 CF3 2



CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
-94-
Compd.Rs Rs R, R, R,s n Phys. data


No.


13.231SCH3 CH3 OCH3 CH3 C02CH2CH3 2


13.232CH3 H CH3 CH2CH=CH2 H 0


13.233CH3 H CH3 CH2CH=CH2 CH3 0


13.234CH3 H CH3 CH2CH=CH2 CF3 0


13.235CH3 H CH3 CH2CH=CH2 COZCH2CH3 0


13.236CH3 H CH3 CH2CH=CH2 H 1


13.237CH3 H CH3 CHZCH=CH2 CH3 1


13.238CH3 H CH3 CH2CH=CH2 CF3 1


13.239CH3 H CH3 CH2CH=CHz COZCH2CH3 1


13.240CH3 H CH3 CHZCH=CH2 H 2 viscous oil


13.241CH3 H CH3 CH2CH=CH2 CH3 2


13.242CH3 H CH3 CH2CH=CH2 CF3 2


13.243CH3 H CH3 CH2CCH C02CH2CH3 2


13.244CH3 H CH3 CH2CCH H 0


13.245CH3 H CH3 CH2CCH CH3 0


13.246CH3 H CH3 CH2CCH CF3 0


13.247CH3 H CH3 CH2CCH C02CH2CH3 0


13.248CH3 H CH3 CH2CCH H 1


13.249CH3 H CH3 CH2CCH CH3 1


13.250CH3 H CH3 CH2CCH CF3 i


13.251CH3 H CH3 CH2CCH C02CHZCH3 1


13.252CH3 H CH3 CH2CCH H 2 viscous oit


13.253CH3 H CH3 CH2CCH CH3 2


13.254CH3 H CH3 CH2CCH CF3 2


13.255CH3 H CH3 CH2CCH C02CH2CH3 2


13.256CH3 CH3 CH3 CH2CH=CH2 H 0


13.257CH3 CH3 CH3 CH2CH=CH2 CH3 0


13.258CH3 CH3 CH3 CH2CH=CH2 CF3 0


13.259CH3 CH3 CH3 CH2CH=CH2 C02CH2CH3 0



CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
-95-
Compd.Rs Rs R, R, R,e n Phys. data


No.


13.260CH3 CH3 CH3 CH2CH=CHZ H 1


13.261CH3 CH3 CH3 CH2CH=CH2 CH3 1


13.262CH3 CH3 CH3 CH2CH=CHz CF3 1


13.263CH3 CH3 CH3 CH2CH=CH2 C02CH2CH3 1


13.264CH3 CHs CH3 CH2CH=CH2 H 2


13.265CH3 CH3 CH3 CH2CH=CH2 CH3 2


13.266CH3 CH3 CH3 CH2CH=CH2 CF3 2


13.267CH3 CH3 CH3 CH2CCH C02CH2CH3 2


13.268CH3 CH3 CH3 CH2CCH H 0


13.269CH3 CH3 CH3 CH2CCH CH3 0


13.270CH3 CH3 CH3 CH2CCH CF3 0


13.271CH3 CH3 CH3 CH2CCH COZCH2CH3 0


13.272CH3 CH3 CH3 CH2CCH H 1


13.273CH3 CH3 CH3 CH2CCH CH3 1


13.274CH3 CH3 CH3 CH2CCH CF3 1


13.275CH3 CH3 CH3 CH2CCH C02CH2CH3 1


13.276CH3 CH3 CH3 CH2CCH H 2


13.277CH3 CH3 CH3 CHzCCH CH3 2


13.278CH3 CH3 CH3 CH2CCH CF3 2


13.279CH3 CH3 CH3 CH2CCH CO2CH2CH3 2


Table C: Physico-chemical data for prepared compounds in the above-mentioned
Tables i-
6 and A, and also 8-11 and B. The figure before the point indicates the number
of the
Table, e.g. 1.027 indicates in Table 1 compound No. 027 of Table A, and 11.027
indicates
in Table 11 compound No. 027 of Table C.
Compd. Physico-chemical data


No. _


_
1.001 m.p.215-218C


1.002 m.p.180C


1.003 m.p.204-206C




CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
-96-
Compd. ~ Physico-chemical data
1.005 m.p.225-226C


1.008 m.p.213-216C


1.016 m.p.194-196C


1.027 m.p.223-225C


1.029 m.p.220-230C


1.030 m.p.222C


1.031 m.p.263-264C


1.033 m.p.187-189C


1.034 m.p. 220-221
C


2.001 m.p.123-126C


2.002 m.p.127-129C


2.003 m.p.112-114C


2.005 m.p.133-134C


2.008 m.p.173-174C


2.027 m.p.170-172C


2.028 m.p. 168-171
C


2.029 m.p.173-174C


2.030 m.p.252C


?.033 m.p.132-135C


2.034 m.p.206C


2.807 m.p.134-135C


3.027 m.p.183-184C


3.029 m.p.185-186C


3.033 m.p. 141-144C


5.027 resin


5.005 resin


5.027 m.p.194-195C


6.029 m.p.189-190C


x.001 m.p.129-130C


3.027 m.p.178-180C


10.001 m.p.191-193C


10.003 m.p.192-193C




CA 02291101 1999-11-24
WO 99/09023 - 97 - PCT/EP98/05247
Compd. Physico-chemical data


No.


10.018 m.p.199-200C


10.027 m.p.230-233C


10.029 m.p.191-192C


10.033 m.p.222-224C


1 i .001 m.p. 185-188C


11.027 m.p.216-218C


11.040 m.p.117-120C


11.066 m.p.213-215C


Examples of specific formulations for compounds of formula l, such as
emuisifiable concen-
trates, solutions, wettable powders, coated granules, extruder grannies, dusts
and suspen-
sion concentrates, are described on pages 9 to 13 of WO 97/34485.
Bioiog~ical Exams Ides
Example B1 ~ Herbicidal action prior to emergence of the plants (hre-emergence
actionl
Monocotyledonous and dicotyledonous test plants are sown in standard soil in
plastics pots.
Immediately after sowing, the test compounds, in the form of an aqueous
suspension or
emulsion prepared from a 25 % wettable powder (Example F3, b), as described,
for
example, in WO 97/34485, or in the form of an emulsion (prepared from a 25
emulsifiable concentrate (Example F1, c), as described, for example, in WO
97/34485), are
applied by spraying in a concentration corresponding to 2000 g of active
lngredient/ha (500
litres waterlha). The test plants are then grown in a greenhouse under optimum
conditions.
After a test duration of 3 weeks, the test is evaluated in accordance with a
scale of nine
ratings (1 = total damage, 9 = no action). Ratings of from 1 to 4 (especially
from 1 to 3)
indicate good to very good herbicidal action.
Test plants: Cyperus, Sinapis, Solanum
The compounds according to the invention exhibit good herbicidal action.
Examples of the good herbicidal activity of the compounds of formula I are
given in
Table B1.
*rB


CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
-98
Table B1: Pre-emergence action:
Test plant: Cyperus Sinapis Solanum Conc.


[g ./ha]
a.i


Compound
No.


2.001 6 2 2 2000


2.003 1 1 1 2000


2.027 3 2 2 2000


2.029 1 1 1 2000


2.034 3 5 3 2000


2.807 2 2 5 2000


3.027 3 1 1 2000


6.029 3 2 2 2000


9.001 3 2 1 2000


10.001 4 5 3 2000


10.027 3 3 2 2000


11.027 4 4 1 2000


12.012 3 7 3 2000


13.007 2 2 2 2000


13.022 3 2 2 2000


13.030 4 4 2 2000


13.038 3 2 2 2000


The same results are obtained when compounds of formula I are formulated in
accordance
with Examples F2 to F8, as described, for example, in WO 97/34485.
Example B2: Post-emer ence herbicidal action
In a greenhouse, monocotyledonous and dicotyisdonous test plants are grown in
standard
soil in plastics pots and at the 4- to 6-leaf stage are sprayed with an
aqueous suspension or
emulsion of the test compounds of formula I, prepared from a 25 % wettable
powder
(Example F3, b), as described, for example, in WO 97134485, or in the form of
an emulsion
(prepared from a 25 % emulsifiable concentrate (Example F1, c), as described,
for example,
in WO 97/34485), in a concentration corresponding to 2000 g of active
ingredient/ha
(500 litres water/ha). The test plants are then grown on in a greenhouse under
optimum
conditions. After a test duration of about 18 days, the test is evaluated in
accordance with a


CA 02291101 1999-11-24
WO 99/09023 PCT/EP98105247
-99-
scale of nine ratings (1 = total damage, 9 = no action}. Ratings of from 1 to
4 (especially
from 1 to 3) indicate good to very good herbicidal action.
Test plants: Setaria, Sinapis, Solanum, Stellaria
In this test too, the compounds of formula I exhibit strong herbicidal action.
Examples of the good herbicidal activity of the compounds of formula I are
given in
Table B2.
Table B2: Post-emergence action:
Test plant: Sinapis Solanum StellariaConc.
Setaria


[g a.i./haj


Compd.
No.


2.001 3 1 2 4 2000


2.002 6 2 1 4 2000


2.003 4 2 2 3 2000


2.005 4 2 2 3 2000


2.008 5 2 2 2 2000


2.027 3 1 2 3 2000


2.028 3 2 2 3 2000


2.029 5 2 2 2 2000


2.030 5 2 2 2 2000


2.034 3 2 2 3 2000


2.807 3 2 1 2 2000


3.027 4 1 1 4 2000


3.029 5 2 2 2 2000


5.027 3 2 1 2 2000


6.005 2 2 2 2 2000


6.027 5 1 4 3 2000


6.029 7 1 1 2 2000


7.027 8 2 2 4 2000


9.001 4 1 1 3 2000


9.027 3 2 2 4 2000


10.001 1 1 3 2000
3




CA 02291101 1999-11-24
WO 99/09023 PCT/EP98/05247
- 100 -
10.0033 1 2 3 2000


10.0163 2 3 3 2000


10.0273 1 2 4 2000


10.0293 3 2 3 2000


11.0012 1 2 3 2000


11.0272 2 2 2 2000


11.0401 2 2 2 2000


11.0662 1 2 2 2000


12.0123 1 1 3 2000


13.0014 1 1 3 2000


13.0073 1 2 2 2000


13.0225 1 1 2 2000


13.0305 1 1 2 2000


13.0343 1 1 3 2000


13.0383 1 1 2 2000


13.0424 1 1 2 2000


13.0586 2 2 3 2000


13.0597 3 2 4 2000


13.0717 2 1 2 2000


13.0794 1 1 3 2000


13.0806 1 1 2 2000


13.1582 1 1 2 2000


13.1593 3 3 3 2000


13.1672 1 1 2 2000


13.1682 2 2 2 2000


13.2166 2 4 2 2000


13.2403 1 2 3 2000


13.2523 3 2 3 2000


The same results are obtained when compounds of formula I are formulated in
accordance
with Examples F2 to F8, as described, for example, in WO 97/34485.

Representative Drawing