Note: Descriptions are shown in the official language in which they were submitted.
CA 022~7080 1998-12-01
PYRIMIDINE-4-CARBOXYLIC ACID AMIDES
The present invention relates to pyrimidine-4-carboxamides of the
S formula I
R3 Y
R2 ~ N-Rs
l l
N ~ N R4 (I)
S (O) n-Rl
15 and salts and N-oxides thereof where:
Rl is Cl-C8-alkyl, it being possible for these radicals to be
partially or fully halogenated and/or to carry one to three
of the following groups: cyano, Cl-C4-alkoxyalkyl, Cl-C4-halo-
alkyl, Cl-C4-alkoxy, Cl-C4-haloalkoxy, Cl-C4-alkylthio,
Cl-C4-alkoxycarbonyl, C3-C7-cycloalkyl, C3-C7-cycloalkenyl,
aryl, aryloxy and hetaryl, it being in turn possible for the
cyclic radicals to carry one to three of the following
substituents: halogen, cyano, Cl-C4-alkyl, Cl-C4-alkoxyalkyl,
Cl-C4-haloalkyl, Cl-C4-alkoxy, Cl-C4-haloalkoxy, Cl-C4-alkyl-
thio, Cl-C4-alkoxycarbonyl, aryl, aryloxy and hetaryl, or
is aryl, it being possible for this radical to carry one or,
independently of one another, two or three of the following
groups: halogen, cyano, Cl-C4-alkyl, Cl-C4-alkoxyalkyl,
Cl-C4-haloalkyl, Cl-C4-alkoxy, Cl-C4-haloalkoxy, Cl-C4-alkyl-
thio, Cl-C4-alkoxycarbonyl, aryl, aryloxy and hetaryl, it
being in turn possible for the cyclic substituents to carry
one or, independently of one another, two or three of the
following substituents: halogen, cyano, Cl-C4-alkyl,
Cl-C4-alkoxyalkyl, Cl-C4-haloalkyl, Cl-C4-alkoxy, Cl-C4-halo-
alkoxy, Cl-C4-alkylthio and Cl-C4-alkoxycarbonyl;
n is 0, 1 or 2;
R2 is hydrogen, hydroxyl, halogen, Cl-C8-alkyl, Cl-C8-haloalkyl,
Cl-C8-alkoxy, Cl-C8-haloalkoxy;
R3 is hydrogen, hydroxyl, halogen, Cl-Cg-alkyl, Cl-C8-haloalkyl,
Cl-C8-alkoxy, Cl-C8-haloalkoxy;
,
0050/46965 CA 022~7080 1998-12-01
one of the radicals R2 and R3 in each case always being
hydrogen;
Y is oxygen or sulfur;
R4 is hydrogen or Cl-Cg-alkyl which may be partially or fully
halogenated or C3-C7-cycloalkyl which may be partially or
fully halogenated;
10 Rs is Cl-C8-alkyl, it being possible for these radicals to be
partially or fully halogenated and/or to carry one or,
independently of one another, two or three of the following
groups: cyano, Cl-Cg-alkoxyalkyl, Cl-C4-haloalkyl,
Cl-C4-alkoxy, Cl-C4-haloalkoxy, Cl-C4-alkylthio, Cl-C4-alkoxy-
carbonyl, C3-C7-cycloalkyl, C3-C7-cycloalkenyl, aryl, aryloxy
and hetaryl, it being in turn possible for the cyclic
radicals to carry one or, independently of one another, two
or three of the following substituents: halogen, cyano,
Cl-C4-alkyl, Cl-C4-alkoxyalkyl, Cl-C4-haloalkyl, Cl-C4-alkoxy,
Cl-C4-haloalkoxy, Cl-C4-alkylthio, Cl-C4-alkoxycarbonyl, aryl,
aryloxy and hetaryl, or
is C3-C7-cycloalkyl, it being possible for this radical to
carry one or, independently of one another, two or three of
the following groups: halogen, Cl-C4-alkyl, Cl-C4-haloalkyl
and Cl-C4-alkoxy, or
is aryl, it being possible for this radical to carry one or,
independently of one another, two or three of the following
groups: halogen, cyano, Cl-C4-alkyl, Cl-C4-alkoxyalkyl,
Cl-C4-haloalkyl, Cl-C4-alkoxy, Cl-C4-haloalkoxy, Cl-C4-alkyl-
thio, Cl-C4-alkoxycarbonyl, aryl, aryloxy and hetaryl, it
being in turn possible for the cyclic substituents to carry
one or, independently of one another, two or three of the
following substituents: halogen, cyano, Cl-C4-alkyl,
Cl-C4-alkoxyalkyl, Cl-C4-haloalkyl, Cl-C4-alkoxy, Cl-C4-halo-
alkoxy, Cl-C4-alkylthio and Cl-C4-alkoxycarbonyl.
Additionally, the invention relates to compositions comprising
40 the compounds I and to the use of the compounds I and the
compositions for controlling harmful fungi.
Compounds of the type I having fungicidal activity are known from
EP-A 569 912 and WO-A 95/25 723.
0050/46965 CA 022~7080 1998-12-01
However, the activity of the compounds described in the
abovementioned publications against harmful fungi is not
satisfactory.
5 It is an object of the present invention to provide novel
pyrimidine-4-carboxamides having improved properties, in
particular a higher activity, and additionally a broad spectrum
of activity in the control of harmful fungi.
10 We have found that this object is achieved by the above-defined
compounds I, by compositions comprising them, and by their use
- and the use of the compositions for controlling harmful fungi.
The compounds I can be prepared in a conventional manner or
15 similar to known methods, as is exemplified in the three
preparation processes below.
Preparation process 1
20 The pyrimidine-4-carboxamides I where
Rl = methyl;
R2 = chlorine;
R3 = hydrogen;
25 Y = 0 and
n = 0, 1 or 2
can be obtained, for example, (cf. Scheme 1 below) by initially
reacting a compound II with S-methylisothiourea sulfate (III) to
30 give 4-hydroxypyrimidine-6-carboxylic acid IV (cf. J. Org. Chem.
26 (1961), 2755). After the chlorination of the hydroxyl
function, which is carried out in a conventional manner and
yields the compounds V, the compounds V are reacted with
amines VI to give the amides I (n = 0). Compounds I where n is 1
35 or 2 are accessible from these amides by oxidation.
0050/46965 CA 022~7080 lss8-l2-ol
Scheme 1
O O- Na+ NH2
HsC20--C--C = CH-- COOC2Hs + (H2N-C-SCH3)+2 SOg2~
II III
O O y
HO ~ ~ OH Cl ~ Cl HN-Rs
I POCl3 I VI
N ~ N ~ N ~ N
S-CH3 S-CH3
IV V
o
Cl ~ ~ N-R5 oxidation
l ll ¦ ~ I (n = 1 or 2)
N ~ N y
S-CH3
I (n = 0)
The amines VI are known or can be obtained in a simple manner
(cf. Houben-Weyl, Methoden der Organischen Chemie, Georg Thieme
Verlag, Stuttgart, Volume XI/l, 4th Edition, 1957, pages 24 to
262 and pages 360 to 409).
The reaction of the amines VI with the compounds V is preferably
carried out in a solvent such as dichloromethane, tetrahydrofuran
or toluene.
35 Suitable bases are in particular the amines VI themselves, these
being usually recovered from the crude product.
The oxidation of the amides I where n = 0 to give the
corresponding compounds I where n = 1 or 2 can be carried out in
40 a conventional manner (cf. Houben-Weyl, Methoden der Organischen
Chemie, Georg Thieme Verlag, Stuttgart, Volume Ell, 4th Edition,
1985, pages 665-850, in particular pages 702-718 (Subvolume I);
ibid., pages 1129-1256, in particular pages 1195-1204 (Subvolume
II); ibid., Vol. IX, 4th Edition, 1955, p. 222 ff.).
.
0050/46965 CA 022~7080 1998-12-01
Suitable oxidizing agents are, for example, hydrogen peroxide,
organic peroxides such as peracetic acid, trifluoroperacetic
acid, m-chloroperbenzoic acid, tert-butyl hydroperoxide and
tert-butyl hypochloride, and inorganic compounds such as sodium
5 metaiodate, chromic acid and nitric acid.
Suitable for completely oxidizing the sulfur are in particular
hydrogen peroxide, organic peroxides such as peracetic acid,
trifluoroperacetic acid and m-chloroperbenzoic acid, and also
10 inorganic oxidizing agents such as potassium permanganate. When
using an inorganic oxidizing agent, the addition of a catalyst,
for example tungstate, can promote the reaction.
Particularly advantageous is a mixture of sodium tungstate and
15 hydrogen peroxide.
As a rule, the reaction is carried out in an inert solvent,
suitable solvents being, depending on the oxidizing agent, for
example organic acids such as acetic acid, trichloroacetic acid
20 and propionic acid, chlorinated hydrocarbons such as methylene
chloride, chloroform and l,2-dichloroethane, aromatic
hydrocarbons or halogenated hydrocarbons such as benzene,
chlorobenzene and toluene, protic solvents such as methanol and
ethanol, or water. Mixtures of the solvents mentioned are also
25 suitable.
The reaction temperature is generally from (-30)~C to the boiling
point of the respective reaction mixture, for the partial
oxidation of the sulfur more in the lower temperature range, for
30 the complete oxidation preferably from 10~C to the boiling point.
The reaction is particularly preferably carried out at from 0 to
40~C.
Depending on the desired target product I where n = 1 or 2,
35 approximately equimolar amounts of oxidizing agent or an about
twofold molar excess is used.
Furthermore, the compounds of the formula I can be converted into
their N-oxides in a conventional manner tcf. for example
40 A. Albini and S. Pietra, Heterocyclic N-Oxides, CRC-Press Inc.,
Boca Raton, USA l991i H.S. Mosher et al., Org. Synth. Coll.
Vol. IV 1963, page 828; E.C. Taylor et al., Org. Synth. Coll.
Vol. IV 1963, page 704; T.W. Bell et al., Synth. 69 (1990), 226).
45 Examples of the oxidizing agents conventionally used for the
oxidation include peracetic acid, trifluoroperacetic acid,
perbenzoic acid, m-chloroperbenzoic acid, monopermaleic acid,
0050/46965 CA 022~7080 1998-12-01
magnesium monoperoxyphthalate, sodium perborate, Oxone~ (contains
peroxomonosulfate), pertungstic acid and hydrogen peroxide.
Suitable solvents are, for example, water, sulfuric acid,
5 carboxylic acids such as acetic acid and trifluoroacetic acid and
halogenated hydrocarbons such as dichloromethane and chloroform.
The oxidation usually succeeds at temperatures of from 0~C to the
boiling point of the reaction mixture.
The oxidizing agent is usually employed in at least equimolar
amounts, based on the starting material. However, a large excess
of oxidizing agent has proved to be particularly advantageous.
15 Preparation process 2
- The pyrimidine-4-carboxamides I where
Rl = methyl;
20 R2 = hydrogen;
R3 = bromine;
Y = 0 and
n = 0, 1 or 2
25 are obtained, for example (cf. Scheme 2 below), by reacting
mucobromic acid VII with S-methylisothiourea sulfate (III) to
give 5-bromopyrimidine-6-carboxylic acids VIII (cf. J. Chem. Soc.
1953, pages 3129-3131) and then proceeding as described in
preparation example 1.
Br O
Br ~ r NH2 ~ OH
HO ~ O (H2N-C-SCH3)+2 so42- ~ N ~ N
VII S-CH3
VIII
Alternatively, in particular when preparing the corresponding
amides I, the 5-bromopyrimidine-6-carboxylic acids VIII are
converted into acyl cyanides or anhydrides (cf. Tetrahedron
Letters 18 (1973), 1595 - 1598, or Houben-Weyl~, Volume 15/1,
45 page 28 to page 32). The carboxy-activated acyl cyanides are
prepared for example by the reaction with diethyl
cyanophosphonate, in particular in an inert solvent such as
, .
0050/46965 CA 022~7080 1998-12-01
tetrahydrofuran or toluene. The carboxy-activated anhydrides are
prepared by reaction with chloroformates such as iso-butyl
chloroformate in the presence of bases and, if appropriate, in an
inert solvent such as toluene or tetrahydrofuran.
Preparation process 3
The pyrimidine-4-carboxamides I where
10 Rl = methyl;
R2 = hydrogen;
R3 = hydrogen;
Y = 0 and
n = 0, 1 or 2
are obtained, for example, by dehalogenating the compounds VIII
(cf. preparation process 2) according to Acta Chem. Scand. ~n
(1986), 588-592 or J. Med. Chem. 29 (1986), 1374-80 and then
proceeding as described in preparation process 1.
Depending on the nature of the substituents, the compounds of the
formula I can in some cases be present as geometric and/or
optical isomers or isomer mixtures. Both the pure isomers and the
mixtures of isomers exhibit the fungicidal action.
The salts of the acid-stable compounds I which contain basic
centers, especially basic nitrogen atoms, in particular with
mineral acids such as sulfuric acid and phosphoric acid or Lewis
acids such as zinc chloride, are also part of the invention.
30 Customarily, in this case the nature of the salt does not matter.
According to the invention, those salts are preferred which do
not damage the plants, areas, materials or spaces to be kept free
from harmful fungi and do not adversely affect the action of the
compounds I. Of particular importance are salts which are
35 suitable for agricultural purposes.
The salts of the compounds I are accessible in a manner known per
se, especially by reacting the corresponding compounds I with the
acids mentioned in water or an inert organic solvent at from
40 (-80) to 120 C, preferably from 0 to 60 C.
In the definitions of the compounds I given at the beginning,
collective terms were used which are generally representative of
the following substituents:
halogen: fluorine, chlorine, bromine and iodine;
- ~ 0050/46965 CA 022~7080 1998-12-01
alkyl: straight-chain or branched alkyl groups having 1 to 8
carbon atoms, eg. C1-C6-alkyl such as methyl, ethyl, n-propyl,
1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl,
1,1-dimethylethyl, n-pentyl, 1-methylbutyl, 2-methylbutyl,
5 3-methylbutyl, 1,1-dimethylpropyl, 2,2-dimethylpropyl,
1,2-dimethylpropyl, 1-ethylpropyl, n-hexyl, 1-methylpentyl,
2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethyl-
butyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 1,2-dimethylbutyl,
1,3-dimethylbutyl, 2,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl,
10 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl,
1-ethyl-1-methylpropyl and 1-ethyl-2-methylpropyl;
haloalkyl or partially or fully halogenated alkyl: straight-chain
or branched alkyl groups having 1 to 4 or 8 carbon atoms (as
15 mentioned above), where in these groups the hydrogen atoms can be
partially or fully replaced by halogen atoms (as mentioned
above), eg. C1-C2-haloalkyl such as chloromethyl, dichloromethyl,
trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl,
chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl,
20 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl,
2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-
2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloro-
ethyl and pentafluoroethyl;
25 alkoxy: straight-chain or branched alkoxy groups having 1 to 4
carbon atoms, eg. C1-C3-alkoxy such as methoxy, ethoxy, propoxy
and l-methylethoxy;
alkoxyalkyl: straight-chain or branched alkyl groups having 1 to
30 8 carbon atoms (as mentioned above), which in any desired
position carry a straight-chain or branched alkoxy group (as
mentioned above) having, in the case of C1-C4-alkoxyalkyl, 1 to 4
carbon atoms, such as methoxymethyl, ethoxymethyl,
n-propoxymethyl, n-butoxymethyl, 1-methoxyethyl, 2-methoxyethyl,
35 1-ethoxyethyl, 2-ethoxyethyl, 2-n-propoxyethyl and 2-butoxyethyl;
haloalkoxy: straight-chain or branched alkoxy groups having 1 to
4 carbon atoms (as mentioned above), where in these groups the
hydrogen atoms can be partially or fully replaced by halogen
40 atoms (as mentioned above), eg. C1-C2-haloalkoxy such as
chloromethoxy, dichloromethoxy, trichloromethoxy, fluoromethoxy,
difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy,
dichlorofluoromethoxy, chlorodifluoromethoxy, 1-fluoroethoxy,
2-fluoroethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy,
45 2-chloro-2-fluoroethoxy, 2-chloro-2,2-difluoroethoxy,
~ 0050/46965 CA 022~7080 1998-12-01
2,2-dichloro-2-fluoroethoxy, 2,2,2-trichloroethoxy and
pentafluoroethoxy;
alkylthio: straight-chain or branched alkyl groups having 1 to 4
5 carbon atoms (as mentioned above), which are bonded to the
structure via a sulfur atom (-S-), eg. Cl-C4-alkylthio such as
methylthio, ethylthio, propylthio, l-methylethylthio, n-butylthio
and tert-butylthio;
10 alkoxycarbonyl: straight-chain or branched alkoxy groups having 1
to 4 C atoms (as mentioned above), which are bonded to the
structure via a carbonyl group (-CO-);
alkenyl: straight-chain or branched alkenyl groups having 2 to 8
15 carbon atoms and a double bond in any desired position, eg.
C2-C6-alkenyl such as ethenyl, l-propenyl, 2-propenyl, l-methyl-
ethenyl, l-butenyl, 2-butenyl, 3-butenyl, l-methyl-l-propenyl,
2-methyl-1-propenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl,
2-methyl-1-propenyl, 1-methyl-2-propenyl, l-pentenyl, 2-pentenyl,
20 3-pentenyl, 4-pentenyl, l-methyl-l-butenyl, 2-methyl-1-butenyl,
3-methyl-1-butenyl, 1-methyl-2-butenyl, 2-methyl-2-butenyl,
3-methyl-2-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl,
3-methyl-3-butenyl, 1,1-dimethyl-2-propenyl, 1,2-dimethyl-1-
propenyl, 1,2-dimethyl-2-propenyl, l-ethyl-l-propenyl,
25 1-ethyl-2-propenyl, l-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl,
5-hexenyl, l-methyl-l-pentenyl, 2-methyl-1-pentenyl, 3-methyl-
l-pentenyl, 4-methyl-1-pentenyl, 1-methyl-2-pentenyl, 2-methyl-
2-pentenyl, 3-methyl-2-pentenyl, 4-methyl-2-pentenyl, l-methyl-
3-pentenyl, 2-methyl-3-pentenyl, 3-methyl-3-pentenyl, 4-methyl-
30 3-pentenyl, 1-methyl-4-pentenyl, 2-methyl-4-pentenyl, 3-methyl-
4-pentenyl, 4-methyl-4-pentenyl, 1,1-dimethyl-2-butenyl,
1,1-dimethyl-3-butenyl, 1,2-dimethyl-1-butenyl, 1,2-dimethyl-
2-butenyl, 1,2-dimethyl-3-butenyl, 1,3-dimethyl-1-butenyl,
1,3-dimethyl-2-butenyl, 1,3-dimethyl-3-butenyl, 2,2-dimethyl-
35 3-butenyl, 2,3-dimethyl-1-butenyl, 2,3-dimethyl-2-butenyl,
2,3-dimethyl-3-butenyl, 3,3-dimethyl-1-butenyl, 3,3-dimethyl-
2-butenyl, l-ethyl-l-butenyl, 1-ethyl-2-butenyl, l-ethyl-
3-butenyl, 2-ethyl-1-butenyl, 2-ethyl-2-butenyl, 2-ethyl-
3-butenyl, 1,1,2-trimethyl-2-propenyl, l-ethyl-l-methyl-
40 2-propenyl, 1-ethyl-2-methyl-1-propenyl and 1-ethyl-2-methyl-
2-propenyl;
alkynyl: straight-chain or branched alkynyl groups having 2 to 8
carbon atoms and a triple bond in any desired position, eg.
45 C2-C6-alkynyl such as ethynyl, l-propynyl, 2-propynyl, l-butynyl,
2-butynyl, 3-butynyl, 1-methyl-2-propynyl, l-pentynyl,
2-pentynyl, 3-pentynyl, 4-pentynyl, 1-methyl-2-butynyl, l-methyl-
, . _ _ .......................... . .. ~ ........ .. ....
0050/46965 CA 022~7080 1998-12-01
3-butynyl, 2-methyl-3-butynyl, 3-methyl-1-butynyl, l,l-dimethyl-
2-propynyl, 1-ethyl-2-propynyl, l-hexynyl, 2-hexynyl, 3-hexynyl,
4-hexynyl, S-hexynyl, l-methyl-2-pentynyl, 1-methyl-3-pentynyl,
l-methyl-4-pentynyl, 2-methyl-3-pentynyl, 2-methyl-4-pentynyl,
5 3-methyl-1-pentynyl, 3-methyl-4-pentynyl, 4-methyl-1-pentynyl,
4-methyl-2-pentynyl, 1,1-dimethyl-2-butynyl, l,l-dimethyl-
3-butynyl, 1,2-dimethyl-3-butynyl, 2,2-dimethyl-3-butynyl,
3,3-dimethyl-1-butYnyl, l-ethyl-2-butynyl, 1-ethyl-3-butynyl,
2-ethyl-3-butynyl and 1-ethyl-1-methyl-2-propynyl;
cycloalkyl: monocyclic alkyl groups having 3 to 7 carbon ring
members, eg. C3-C7-cycloalkyl such as cyclopropyl, cyclobutyl,
cyclopentyl, cyclohexyl and cycloheptyl;
15 cycloalkenyl: monocyclic alkyl groups having 5 to 7 carbon ring
members which contain one or more double bonds, eg. C5-C7-cyclo-
alkenyl such as cyclopentenyl, cyclohexenyl and cycloheptenyl;
aryl: monocyclic or polycyclic aromatic groups having 6 to 10 C
20 atoms, such as phenyl and naphthyl;
arylalkyl: aryl groups (as mentioned above), which in the case of
aryl-(Cl-Cg)-alkyl are bonded to the structure via alkyl groups
having 1 to 4 carbon atoms (as mentioned above), eg.
25 phenyl-(Cl-C4)-alkyl such as benzyl, 2-phenylethyl, 3-phenyl-
propyl, 4-phenylbutyl, l-phenylethyl, l-phenylpropyl and
l-phenylbutyl;
aryloxy: aryl groups (as mentioned above), which are bonded to
30 the structure via an oxygen atom (-O-), such as phenoxy,
l-naphthoxy and 2-naphthoxy;
hetaryl: aromatic mono- or polycyclic radicals which in addition
to carbon ring members can additionally contain 1 to 4 nitrogen
35 atoms or 1 to 3 nitrogen atoms and an oxygen or a sulfur atom or
an oxygen or a sulfur atom, eg.:
- 5-membered hetaryl, containing 1 to 3 nitrogen atoms:
5-membered ring hetaryl groups which in addition to carbon
atoms can contain 1 to 3 nitrogen atoms as ring members, eg.
2-pyrrolyl, 3-pyrrolyl, 3-pyrazolyl, 4-pyrazolyl,
5-pyrazolyl, 2-imidazolyl, 4-imidazolyl, 1,2,4-triazol-3-yl
and l,3,4-triazol-2-yl;
5-membered hetaryl, containing 1 to 4 nitrogen atoms or 1 to
3 nitrogen atoms and 1 sulfur atom or oxygen atom or 1 oxygen
or 1 sulfur atom: S-membered ring hetaryl groups which in
0050/46965 CA 022~7080 1998-12-01
11
addition to carbon atoms can contain 1 to 4 nitrogen atoms or
1 to 3 nitrogen atoms and 1 sulfur or oxygen atom or 1 oxygen
or sulfur atom as ring members, eg. 2-furyl, 3-furyl,
2-thienyl, 3-thienyl~, 2-pyrrolyl, 3-pyrrolyl, 3-isoxazolyl,
4-isoxazolyl, 5-isoxazolyl, 3-isothiazolyl, 4-isothiazolyl,
5-isothiazolyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl,
2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 2-thiazolyl, 4-thiazolyl,
5-thiazolyl, 2-imidazolyl, 4-imidazolyl, 1,2,4-oxadiazol-
3-yl, 1,2,4-oxadiazol-5-yl, 1,2,4-thiadiazol-3-yl,
1,2,4-thiadiazol-5-yl, 1,2,4-triazol-3-yl, 1,3,4-oxadiazol-
2-yl, 1,3,4-thiadiazol-2-yl, 1,3,4-triazol- 2-yl;
- benzo-fused 5-membered hetaryl, containing 1 to 3 nitrogen
atoms or 1 nitrogen atom and/or an oxygen or sulfur atom:
5-membered ring hetaryl groups which in addition to carbon
atoms can contain 1 to 4 nitrogen atoms or 1 to 3 nitrogen
atoms and 1 sulfur or oxygen atom or 1 oxygen or a sulfur
atom as ring members, and in which 2 adjacent carbon ring
members or 1 nitrogen and 1 adjacent carbon ring member can
be bridged by a buta-1,3-diene-1,4-diyl group;
- 5-membered hetaryl bonded via nitrogen, containing 1 to 4
nitrogen atoms, or benzo-fused 5-membered hetaryl bonded via
nitrogen, containing 1 to 3 nitrogen atoms: 5-membered ring
hetaryl groups which in addition to carbon atoms can contain
1 to 4 nitrogen atoms or 1 to 3 nitrogen atoms as ring
members, and in which 2 adjacent carbon ring members or a
nitrogen and an adjacent carbon ring member can be bridged by
a buta-1,3-diene-1,4-diyl group, where these rings are bonded
to the structure via one of the nitrogen ring members;
- 6-membered hetaryl, containing 1 to 3 or 1 to 4 nitrogen
atoms: 6-membered ring hetaryl groups which in addition to
carbon atoms can contain 1 to 3 or 1 to 4 nitrogen atoms as
ring members, eg. 2-pyridinyl, 3-pyridinyl, 4-pyridinyl,
3-pyridazinyl, 4-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl,
5-pyrimidinyl, 2-pyrazinyl, 1,3,5-triazin-2-yl,
1,2,4-triazin-3-yl and 1,2,4,5-tetrazin-3-yl;
40 - benzo-fused 6-membered hetaryl, containing 1 to 4 nitrogen
atoms: 6-membered ring hetaryl groups in which 2 adjacent
carbon ring members can be bridged by a buta-1,3-diene-
1,4-diyl group, eg. quinoline, isoquinoline, quinazoline and
quinoxaline.
0050/46965 CA 022~7080 1998-12-01
12
The statement Upartially or fully halogenatedn is intended to
express that in the groups characterized in this way the hydrogen
atoms can be partially or fully replaced by identical or
different halogen atoms as mentioned above.
With respect to their biological action against harmful fungi,
preference is given to compounds I where the radicals have the
following meanings, namely per se or in combination:
10 Rl is methyl;
n is 1, in particular 2;
R2 is hydroxyl, Cl-cs-alkoxy with or without substitution as
claimed, in particular hydrogen, chlorine, methoxy;
R3 is hydroxyl, Cl-Cg-alkoxy with or without substitution as
claimed, in particular hydrogen, bromine, methoxy;
20 Y is oxygen;
R4 is hydrogen;
R5 is Cl-C6-alkyl with or without substitution, cyclohexyl, in
particular phenyl with or without substitution.
With respect to their biological activity, very particular
preference is given to the compounds I listed in the tables
below.
Table 1
Compounds of the formula I.l
Br ~
U~
~ ~ NH - R5
N~,N (I.l)
o=~~=O
CH3
where for each compound R5 corresponds to one row in Table A.
.. . , , . .. ~, . ,
~ 0050/46965 CA 02257080 1998-12-01
Table 2
Compounds of the formula I.2
Br O
~ NH - R5
N~,N (I.2)
10=o
CH3
where for each compound R5 corresponds to one row in Table A.
Table 3
Compounds of the formula I.3
20OCH3 O
~ NH - R5
N~,N (I.3)
2~o=~~=O
CH3
where for each compound R5 corresponds to one row in Table A.
Table 4
Compounds of the formula I.4
35OCH3 ~
~ NH - R5
N~N (I.4)
40~ =O
CH3
where for each compound R5 corresponds to one row in Table A.
- ~ 0050/46965 CA 022~7080 1998-12-01
14
Table 5
Compounds of the formula I.5
~ NH - R5
N~,N (I.5)
0=-=0
CH3
where for each compound Rs corresponds to one row in Table A.
Table 6
Compounds of the formula I.6
0
~ NH - R5
N~,N (I.6)
~=O
CH3
where for each compound Rs corresponds to one row in Table A.
Table 7
Compounds of the formula I.7
O
CH30 ~ NH - Rs
N~,N (I.7)
o= ~=O
CH3
where for each compound Rs corresponds to one row in Table A.
0050/46965 CA 02257080 1998-12-01
Table 8
Compounds of the formula I.8
O
CH3O ~ NH - Rs
N~,N (I.8)
'-=~
CH3
where for each compound R5 corresponds to one row in Table A.
Table 9
Compounds of the formula I.9
O
Cl ~ NH--Rs
N ~ N (I.9)
o=l=O
CH3
where for each compound R5 corresponds to one row in Table A.
Table 10
Compounds of the formula I.10
O
1~
Cl ~ NH - Rs
N ~ N (I.10)
~~=O
CH3
where for each compound R5 corresponds to one row in Table A.
0050/46g65 CA 022~7080 1998-12-01
Table A
No. R5
A.1 2-CH3- (C6H4)
A.2 3-CH3- (C6H4)
A.3 4-CH3- (C6H4)
A .4 2 - OCH3 - ( 4H4)
A.5 3-OCH3- (C6H4)
10 A.6 4-OCH3- (C6H4)
A.7 2-OC2Hs- (C6H4)
A.8 3-OC2Hs~ (C6H4)
A.9 4-OC2Hs~ (C6H4)
A.10 2-OCH (CH3) 2- (C6H4)
A.11 3-OCH (CH3) 2- (C6H4)
A.12 4-OCH (CH3) 2- (C6H4)
A .13 2 -CN- ( C6H4)
A .14 3 -CN- ( C6H4)
20 A.15 4-CN-(C6H4)
A .16 2 -NO2- ( C6H4)
A.17 3-NO2- (C6H4)
A.18 4-NO2- (C6H4)
25 A.19 2-OH- (C6H4)
A .20 3 -OH- ( C6H4)
A.21 4-OH- (C6H4)
A.22 2-Cl- (C6H4)
30 A.23 3-C1- (C6H4)
A .24 4 -C 1- ( C6H4)
A.25 2-Br- (C6H4)
A.26 3-Br- (C6H4)
A.27 4-Br- (C6H4)
35 A.28 2-F- (C6H4)
A.29 3-F- (C6H4)
A.30 4-F- (C6H4)
A .31 2 -CF3- ( C6H4)
40 A.32 3-CF3- (C6H4)
A.33 4-CF3- (C6H4)
A.34 2-C (CH3) 3- (C6H4)
A.35 3-C (CH3) 3- (C6H4)
45 A.36 4-C (CH3) 3- (C6H4)
A.37 2,3-F2- (C6H3)
A.38 2,4-F2- (C6H3)
~ 0050/46965 CA 022~7080 1998-12-01
17
No. R5
A.39 2,5-F2-(C6H3)
A.40 2,6-F2-(C6H3)
A.41 3~4-F2-(c6H3)
A.42 3~5-F2-(c6H3)
A.43 2,4,5-F3-(C6H2)
A.44 2,4,6-F3-(C6H2)
A.45 3,4,5-F3-(C6H2)
A 46 2 3-C12-(C6H3)
A.47 2,4-Cl2-(C6H3)
A.48 2,5-Cl2-(C6H3)
A.49 2,6-Cl2-(C6H3)
A.50 3,4-Cl2-(C6H3)
A.51 3,5-Cl2-(C6H3)
A.52 2,4,5-c13-(C6H2)
A.53 2,4,6-c13-(C6H2)
A.54 3~4~5-cl3-(c6H2)
A.55 2,3-(CH3)2-(C6H3)
A.56 2,4-(CH3)2-(C6H3)
A.57 2,5-(CH3)2-(C6H3)
A.58 2,6-(CH3)2-(C6H3)
A.59 3,4-(CH3)2-(C6H3)
A.60 3~5-(CH3)2-(C6H3)
A.61 2,4,5-(CH3)3-(C6H2)
A.62 2,4,6-(CH3)3-(C6H2)
A.63 3~4~5-(cH3)3-(c6H2)
A.64 CH2CH2CH2CH3
A.65 CH2CF3
A.65 CH(CH3)-(c6Hs)
35 A.66 C6H5
A.67 cyclo-c6Hll
The compounds I are suita~le for controlling harmful fungi.
Depending on their chemical and physical properties, they may be
formulated with conventional formulation auxiliaries, i.e.
formulation auxiliaries known to a person skilled in the art. The
thus-prepared products are called ~compositions~.
0050/46965 CA 022~7080 1998-12-01
Suitable formulation auxiliaires are, for example, solid or
liquid carriers, surfactants and tackifiers.
Liquid carriers are liquid solvents such as water and organic
5 solvents, the latter, especially when using water as solvent,
acting as auxiliary solvent. Suitable organic solvents are:
aromatics, such as xylene, toluene and alkylnaphthalenes,
chlorinated aromatics or chlorinated aliphatic hydrocarbons, such
as chlorobenzenes, chloroethylenes and methylene chloride,
10 aliphatic hydrocarbons, such as cyclohexane and paraffins, for
example petroleum fractions, alcohols, such as butanol,
iso-butanol, cyclohexanol and glycol and also the corresponding
ethers and esters, ketones, such as acetone, methyl ethyl ketone,
methyl iso-butyl ketone and cyclohexanone, and aprotic dipolar
15 solvents, such as dimethylformamide, N-methyl-2-pyrrolidone and
dimethyl sulfoxide.
Suitable solid carriers are, for example: ground natural minerals
and mineral earths such as silicas, silicates, kaolins, clays,
20 bole, loess, talc, chalk, limestone, lime, dolomite, magnesium
oxide, quartz, attapulgite, montmorillonite and diatomaceous
earth; ground synthetic materials such as finely divided silica,
ground synthetic aluminum oxide or ground synthetic silicates.
Solid carriers particularly suitable for granules are, for
25 example: crushed and fractionated natural rocks, such as calcite,
marble, pumice and sepiolite; synthetic granules of inorganic and
organic meals; granules of organic material such as sawdust,
coconut shells, maize cobs or tobacco stalks.
30 Suitable surfactants are nonionic and anionic emulsifiers/
foam formers and dispersants:
- polyoxyethylene fatty acid esters, such as lauryl alcohol
polyoxyethylene ether acetate,
35 - polyoxyethylene alkyl ethers or polyoxypropylene alkyl
ethers, for example of iso-tridecylalcohol, and polyoxy-
ethylene fatty alcohol ethers,
- alkylaryl alcohol polyoxyethylene ethers, such as octylphenol
polyoxyethylene ether,
40 - tributylphenol polyoxyethylene ether,
- ethoxylated iso-octyl-, octyl- or nonylphenol or castor oil,
- sorbitol esters,
- arylsulfonic acids, alkylsulfonic acids, alkylsulfuric acids,
- alkali metal salts, alkaline earth metal salts and ammonium
salts of arylsulfonic acids, e.g. ligno-, phenol-,
naphthalene- and dibutylnaphthalenesulfonic acid, of
alkylsulfonic acids, alkylarylsulfonic acids, alkyl, lauryl
0050/46965 CA 022~7080 1998-12-01
19
ether and fatty alcohol sulfates, fatty acids, sulfated
hexa-, hepta- and octadecanols and fatty alcohol glycol
ethers,
- condensates of sulfonated naphthalene and its derivatives
with formaldehyde,
- condensates of naphthalenesulfonic acids with phenol or
formaldehyde,
- protein hydrolyzates and
- in particular as dispersants: lignin-sulfite waste liquors
and methylcellulose.
Suitable tackifiers are, for example: carboxymethylcellulose;
natural and synthetic polymers in the form of powders, granules
or latices such as gum arabic, polyvinyl alcohol and polyvinyl
15 acetate, natural phospholipids such as cephalins and lecithins,
synthetic phospholipids.
Furthermore, the compositions may comprise one or more examples
of the following groups of compounds: colorants, other known
20 active compounds, trace nutrients and other additives.
Suitable colorants are, for example, inorganic pigments, such as
iron oxide, titanium oxide, Prussian Blue, further organic
dyestuffs, such as alizarin dyestuffs, azo dyestuffs and metal
25 phthalocyanine dyestuffs. Other known active compounds are, for
example, other fungicides, and also insecticides, acaricides,
herbicides and growth regulators. Trace nutrients are, for
example, salts of iron, manganese, boron, copper, cobalt,
molybdenum and zinc. Further suitable additives are, for example,
30 mineral and vegetable oils.
In addition, the compositions may be mixed with other mixing
partners of practical importance, such as fertilizers and other
ready-to-use active compound compositions.
The compositions are prepared in a conventional manner, i.e.
depending on the chemical and physical properties of the
compounds used, for example by mixing, joint grinding, spraying
on, extrusion, granulation, or dissolution in water, the latter,
40 if necessary, with the aid of an organic solvent. Powders,
granules and dusts can be obtained for example by mixing or
grinding the compounds I together with a solid carrier.
0050/46965 CA 022~7080 1998-12-01
Depending on the compounds used, the compositions are, for
example, solutions, emulsions, suspensions, powders, foams,
pastes, granules, aerosols or microencapsulations in polymeric
substances or in coatings for seeds.
For application, the compositions, which are usually commercially
available as concentrates, are, if necessary, dissolved, diluted,
etc. as is common practice, in the case of spray powders, water-
dispersible granules, emulsifiable concentrates, dispersions and
10 also in the case of some microgranules normally by using water.
Dusts, granules and spray-solutions are usually not diluted any
further with other inert substances prior to application.
The compositions are applied in a manner known per se, for
15 example by spraying, atomizing, dusting, scattering or wetting.
Generally, the plants are sprayed or dusted with the
compositions. Alternatively or additionally, the seeds of the
plants are treated in a m~nner known per se.
20 Examples of such preparations are:
I. a solution of 90 parts by weight of a compound I according
to the invention and 10 parts by weight of N-methyl-
2-pyrrolidone, which is suitable for use in the form of
microdrops;
II. a mixture of 20 parts by weight of a compound I according
to the invention, 80 parts by weight of xylene, 10 parts by
weight of the adduct of 8 to 10 mol of ethylene oxide to
1 mol of oleic acid N-monoethanolamide, 5 parts by weight
of calcium dodecylbenzenesulfonate, 5 parts by weight of
the adduct of 40 mol of ethylene oxide to 1 mol of castor
oil: a dispersion is obtained by finely distributing the
solution in water;
III. an a~ueous disperson of 20 parts by weight of a compound I
according to the invention, 40 parts by weight of
cyclohexanone, 30 parts by weight of isobutanol, 20 parts
by weight of the adduct of 40 mol of ethylene oxide to
1 mol of castor oil;
IV. an aqueous dispersion of 20 parts by weight of a compound I
according to the invention, 25 parts by weight of cyclo-
hexanol, 65 parts by weight of a petroleum fraction of
boiling point 210 to 280~C and 10 parts by weight of the
adduct of 40 mol of ethylene oxide to 1 mol of castor oil;
0050/46965 CA 022~7080 1998-12-01
21
V. a mixture, ground in a hAmmer mill, of 80 parts by weight
of a compound I according to the invention, 3 parts by
weight of sodium diisobutylnaphthalene-l-sulfonate,
10 parts by weight of the sodium salt of a lignosulfonic
acid from a sulfite waste liquor and 7 parts by weight of
pulverulent silica gel: a spray mixture is obtained by
finely distributing the mixture in water;
VI. an intimate mixture of 3 parts by weight of a compound I
according to the invention and 97 parts by weight of finely
divided kaolini this dust comprises 3% by weight of active
ingredient;
VII. an intimate mixture of 30 parts by weight of a compound I
according to the invention, 92 parts by weight of
pulverulent silica gel and 8 parts by weight of paraffin
oil which has been sprayed onto the surface of this silica
gel; this formulation imparts good adhesion to the active
ingredient;
VIII. a stable aqueous dispersion of 40 parts by weight of a
compound I according to the invention, 10 parts by weight
of the sodium salt of a phenolsulfonic acid/urea/
formaldehyde condensate, 2 parts by weight of silica gel
and 48 parts by weight of water, it being possible for this
dispersion to be diluted further;
IX. a stable oily dispersion of 20 parts by weight of a
compound I according to the invention, 2 parts by weight of
calcium dodecylbenzenesulfonate, 8 parts by weight of
fatty alcohol polyglycol ether, 20 parts by weight of the
sodium salt of a phenolsulfonic acid/urea/formaldehyde
condensate and 68 parts by weight of a paraffinic mineral
oil.
If the compounds I are applied as such, a fine distribution is
essential.
The compounds I and the compositions according to the invention
40 have an outstanding activity against a broad spectrum of harmful
fungi (phytopathogenic fungi), in particular from the classes of
the
- Ascomycetes,
45 - Basidiomycetes,
- Deuteromycetes and
~ Phycomycetes.
~ 0050/46965 CA 022~7080 1998-12-01
22
Some of them act systemically and can be employed as foliar- and
soil-acting fungicides.
They are especially important for controlling a large number of
5 fungi in a variety of crop plants, such as wheat, rye, barley,
oats, rice, maize, lawns, cotton, soy, coffee, sugar cane,
grapevines, ~ruit species, ornamentals and vegetable species such
as cucumbers, beans and cucurbits as well as the seeds of these
plants.
The compounds I, their salts and N-oxides and the compositions
according to the invention are applied by treating the harmful
fungi, their habitat, or the seeds, plants, areas, materials or
the spaces to be protected against fungal infection, with a
15 fungicidally active amount of the compositions or of the
compounds I. Application is effected before or after infection by
the fungi.
Specifically, the compositions according to the invention and the
20 compounds I are suitable for controlling the following plant
diseases:
Erysiphe graminis (powdery mildew) in cereals, Erysiphe
cichoracearum and Sphaerotheca fuliginea in cucurbits,
25 Podosphaera leucotricha in apples, Uncinula necator in
grapevines, Puccinia species in cereals, Rhizoctonia species in
cotton, rice and lawns, Ustilago species in cereals and sugar
cane, Venturia inaequalis (scab) in apples, Helminthosporium
species in cereals, Septoria nodorum in wheat, Botrytis cinerea
30 (gray mold) in strawberries, grapevines, ornamentals and
vegetables, Cercospora arachidicola in groundnuts,
Pseudocercosporella herpotrichoides in wheat, barley, Pyricularia
oryzae in rice, Phytophthora infestans in potatoes and tomatoes,
Fusarium and Verticillium species in a variety of plants,
- 35 Plasmopara viticola in grapevines, Pseudoperonospora species in
hops and cucumbers and Alternaria species in vegetables and
fruit.
In general, the fungicidal compositions comprise from 0.1 to 95,
40 preferably from 0.5 to 90, % by weight of active compound.
Depending on the nature of the desired effect, the rates of
application are from 0.01 to 2.0 kg of active compound per ha.
0050/46965 CA 022S7080 1998-12-01
In the treatment of seed, amounts of from 0.001 to 0.1 g,
preferably 0.01 to O.OS g of active compound are generally
required per kilogram of seed.
5 The compositions according to the invention in the use form as
fungicides may also be present together with other active
compounds, e.g. with herbicides, insecticides, growth regulators,
fungicides or else with fertilizers.
10 In many cases, a mixture with fungicides results in a widened
fungicidal spectrum of action.
The following list of fungicides together with which the
compounds according to the invention can be used is intended to
15 illustrate the possible combinations, but not to impose any
limitation:
sulfur, dithiocarbamates and their derivatives, such as iron
dimethyldithiocarbamate, zinc dimethyldithiocarbamate, zinc
20 ethylenebisdithiocarbamate, manganese ethylenebisdithiocarbamate,
manganese zinc ethylenediamine-bis-dithiocarbamate,
tetramethylthiuram disulfide, ammonia complex of zinc
(N,N-ethylene-bis-dithiocarbamate), ammonia complex of zinc
(N,N'-propylene-bis-dithiocarbamate), zinc (N,N'-propylene-
25 bisdithiocarbamate), N,N'-polypropylenebis(thiocarbamoyl)-
disulfidei
nitro derivatives, such as dinitro-(l-methylheptyl)phenyl
crotonate, 2-sec-butyl-4,6-dinitrophenyl-3,3-dimethyl acrylate,
30 2-sec-butyl-4,6-dinitrophenylisopropyl carbonate, di-isopropyl
5-nitroisophthalate;
heterocyclic substances, such as 2-heptadecyl-2-imidazoline
acetate, 2,4-dichloro-6-(o-chloroanilino)-s-triazine, O,O-diethyl
35 phthalimidophosphonothioate, 5-amino-1-[bis(dimethylamino)-
phosphynyl]-3-phenyl-1,2,4-triazole, 2,3-dicyano-1,4-dithio-
anthraquinone, 2-thio-1,3-dithiolo[4,5-b]quinoxaline, methyl
l-(butylcarbamoyl)-2-benzimidazolecarbamate, 2-methoxycarbonyl-
aminobenzimidazole, 2-(furyl-(2))benzimidazole, 2-(thiazolyl-
40 (4))benzimidazole, N-(1,1,2,2-tetrachloroethylthio)tetrahydro-
phthalimide, N-trichloromethylthiotetrahydrophthalimide,
N-trichloromethylthiophthalimide,
N-dichlorofluoromethylthio-N',N'-dimethyl-N-phenylsulfuric
45 diamide, 5-ethoxy-3-trichloromethyl-1,2,3-thiadiazole,
2-thiocyanatomethylthiobenzothiazole, 1,4-dichloro-2,5-dimethoxy-
benzene, 4-(2-chlorophenylhydrazono)-3-methyl-5-isoxazolone,
0050/46965 CA 022~7080 1998-12-01
24
pyridine-2-thio-1-oxide, 8-hydroxyquinoline or its copper salt,
2,3-dihydro-5-carboxanilido-6-methyl-1,4-oxathiine, 2,3-dihydro-
5-carboxanilido-6-methyl-1,4-oxathiine-4,4-dioxide, 2-methyl-
5,6-dihydro-4H-pyran-3-carboxanilide, 2-methylfuran-3-carbox-
5 anilide, 2,5-dimethylfuran-3-carboxanilide, 2,4,5-trimethylfuran-
3-carboxanilide, N-cyclohexyl-2,5-dimethylfuran-3-carboxamide,
N-cyclohexyl-N-methoxy-2,5-dimethylfuran-3-carboxamide,
2-methylbenzanilide, 2-iodobenzanilide, N-formyl-N-morpholine
2,2,2-trichloroethyl acetal, piperazine-1,4-diylbis-
10 (1-(2,2,2-trichloroethyl)formamide, 1-(3,4-dichloroanilino)-
l-formylamino-2,2,2-trichloroethane, 2,6-dimethyl-N-tridecyl-
morpholine or its salts, 2,6-dimethyl-N-cyclododecylmorpholine or
its salts, N-[3-(p-tert-butylphenyl)-2-methylpropyl]-cis-
2,6-dimethylmorpholine, N-[3-(p-tert-butylphenyl)-2-methyl-
15 propyl]piperidine, 1-[2-(2,4-dichlorophenyl)-4-ethyl-1,3-
dioxolan-2-ylethyl]-lH-1,2,4-triazole, 1-[2-(2,4-dichloro-
phenyl)-4-n-propyl-1,3-dioxolan-2-ylethyl]-lH-1,2,4-triazole,
N-(n-propyl)-N-(2,4,6-trichlorophenoxyethyl)-N'-imidazolylurea,
1-(4-chlorophenoxy)-3,3-dimethyl-1-(lH-1,2,4-triazol-1-yl)-
20 2-butanone, (2-chlorophenyl)-(4-chlorophenyl)-5-pyrimidine-
methanol, 5-butyl-2-dimethylamino-4-hydroxy-6-methylpyrimidine,
bis(p-chlorophenyl)-3-pyridinemethanol, 1,2-bis(3-ethoxycarbonyl-
2-thioureido)benzene, 1,2-bis(3-methoxycarbonyl-2-thioureido)-
benzene, [2-(4-chlorophenyl)ethyl]-(1,1-dimethylethyl)-lH-1,2,4-
25 triazole-l-ethanol, and
a variety of fungicides, such as dodecylguanidine acetate,
3-[3-(3,5-dimethyl-2-oxycyclohexyl)-2-hydroxyethyl]glutarimide,
hexachlorobenzene, methyl N-(2,6-dimethylphenyl)-N-(2-furoyl)-
30 DL-alaninate, DL-N-(2,6-dimethylphenyl)-N-(2~-methoxyacetyl)-
alanine methyl ester, N-(2,6-dimethylphenyl)-N-chloroacetyl-
D,L-2-aminobutyrolactone, DL-N-(2,6-dimethylphenyl)-N-(phenyl-
acetyl)alanine methyl ester, 5-methyl-5-vinyl-3-(3,5-dichloro-
phenyl)-2,4-dioxo-1,3-oxazolidine, 3-(3,5-dichlorophenyl)-
35 5-methyl-5-methoxymethyl-1,3-oxazolidine-2,4-dione,
3-(3,5-dichlorophenyl)-1-iso-propylcarbamoylhydantoin,
N-(3,5-dichlorophenyl)-1,2-dimethylcyclopropane-1,2-
dicarboximide, 2-cyano-[N-(ethylaminocarbonyl)-2-methoximino]-
acetamide, l-[2-(2,4-dichlorophenyl)pentyl]-lH-1,2,4-triazole,
40 2,4-difluoro-a-(lH-1,2,4-triazolyl-1-methyl)benzhydryl alcohol,
N-(3-chloro-2,6-dinitro-4-trifluoromethylphenyl)-5-trifluoro-
methyl-3-chloro-2-aminopyridine, 1-((bis-(4-fluorophenyl)methyl-
silyl)methyl)-lH-1,2,4-triazole.
45 Strobilurins, such as methyl E-methoximino-[a-(o-tolyloxy)-
o-tolyl]acetate, methyl E-2-{2-[6-(2-cyanophenoxy)pyridimin-4-yl-
oxy]phenyl}-3-methoxyacrylate, N-methyl-E-methox; m; no-[a-
0050/46965 CA 022~7080 1998-12-01
(2-phenoxyphenyl)]acetamide, N-methyl-E-methoximino-[a-
(2,5-dimethylphenoxy)-o-tolyl]acetamide.
AnilinopyrimidineS, such as N-(4,6-dimethylpyrimidin-2-yl)-
5 aniline, N-[4-methyl-6-(1-propynyl)pyrimidin-2-yl]aniline,
N-(4-methyl-6-cyclopropylpyrimidin-2-yl)aniline.
Phenylpyrroles, such as 4-(2,2-difluoro-1,3-benzodioxol-4-yl)-
pyrrole-3-carbonitrile.
Cinnamamides, such as 3-(4-chlorophenyl)-3-(3,4-dimethoxyphenyl)-
acryloylmorpholide.
(2RS,3SR)-1-[3-(2-chlorophenyl)-2-[4-fluorophenyl]oxiran-2-yl-
15 methyl]-lH-1,2,4-triazole.
Preparation examples
The procedures of the preparation examples below may be employed
20 to prepare further representatives of the compounds I by
modifying the starting materials. The physical data of the
products prepared in this way are listed in the Table Sl below.
1. 2-Methylsulfonyl-5-brOmopyrimidine-4-carboxy-(4-fluoro-
phenyl)amide (compound Sl.10)
a) 2-Thiomethyl-5-bromopyrimidine-4-carboxylic acid was obtained
by the method of J. Chem. Soc. 1953, 3129-21: 56 g
(0.217 mol) of mucobromic acid were dissolved in 800 ml of
water at 50~C, and 60 g (0.217 mol) of S-methylisothiourea
sulfate were added at this temperature. After cooling to room
temperature, 65.8 g (0.651 mol) of triethylamine were added
dropwise with stirring, the temperature being kept at 20~C.
After acidification with concentrated hydrochloric acid, the
product crystallized as a solid (28.0 g, mp. 168-170~C).
b) 2-Thiomethyl-5-bromopyrimidine-4-carbonyl chloride
10.0 g (40 mmol) of 2-thiomethyl-5-bromopyrimidin-
4-carboxylic acid and 50 ml of thionyl chloride were stirred
with 1 ml of DMF for two hours at 80~C. The thionyl chloride
was distilled off and the product was fractionated at
105-110~C and 0.8 mbar. Yield: 9.3 g.
0050/46965 CA 022~7080 1998-12-01
26
c) 2-Thiomethyl-5-bromopyrimidine-4-carboxy-(4-fluorophenyl)-
amide
1.0 g (3.7 mmol) of 2-thiomethyl-5-bromopyrimidine-4-carbonyl
chloride and 0.4 g (4 mmol) of triethylamine were dissolved
in 40 ml of anhydrous toluene, and 0.41 g (3.7 mmol) of
4-fluoroaniline was added with stirring. The mixture was
stirred for 16 hours and washed with 50 ml each of 2 N
hydrochloric acid, 5% strength sodium bicarbonate solution
and water, and the organic phase was dried with sodium
sulfate and concentrated. This gave 1.2 g of 2-thiomethyl-
5-bromopyrimidine-4-carboxy-(4-fluorophenyl)amide (compound
S1.47).
15 d) 2-Methylsulfonyl-5-bromopyrimidine-4-carboxy-(4-fluoro-
phenyl)amide
50 mg of sodium tungstate were added to a mixture of 0.4 g of
30% hydrogen peroxide and 5 ml of glacial acetic acid, and
the mixture was stirred for 15 min. 1.2 g (3.5 mmol) of
2-thiomethyl-5-bromopyrimidine-4-carboxy-(4-fluorophenyl)-
amide dissolved in glacial acetic acid were then added, and
the mixture was stirred at 25~C for 16 hours. On addition of
100 ml of water, the product precipitated in the form of
yellow crystals and was filtered off with suction. This gave
1.1 g of the title compound (mp. 169-174~C, compound S1.10).
2. 2-Methylsulfonylpyrimidine-4-carboxy-(4-fluorophenyl)amide
(compound S1.23)
a) 2-Thiomethylpyrimidine-4-carboxylic acid was prepared by the
method of J. Med. Chem. 29 (1986), 1374-80: 46.8 g
(0.188 mol) of 2-thiomethyl-5-bromopyrimidine-4-carboxylic
acid together with 23 g (0.41 mol) of potassium hydroxide
were dissolved in 800 ml of methanol. After the addition of
10 g of 5% palladium on barium sulfate, a pressure of 10 bar
of hydrogen was applied and the mixture was stirred for
16 hours. The catalyst was filtered off and the filtrate was
diluted with water and acidified to pH 1 using hydrochloric
acid. The product precipitated in the form of light-brown
crystals. Recrystallization from ethanol gave 28.7 g of
2-thiomethylpyrimidine-4-carboxylic acid of melting point
211-215~C.
.
0050/46965 CA 022~7080 1998-12-01
27
b) 2-Thiomethylpyrimidine-4-carboxy-(4-fluorophenyl)amide
0.68 g (4 mmol) of 2-thiomethylpyrimidine-4-carboxylic acid
and 0.44 g (4 mmol) of 4-fluoroaniline were suspended in
50 ml of dichloromethane (puriss.). After the addition of
0.5 g of triethylamine, 0.7 g (4 mmol) of 93% diethyl
cyanophosphonate were added dropwise and the mixture was
stirred at 25~C for 16 hours. 50 ml of dichloromethane were
added, and the mixture was washed twice with 100 ml of 2 N
aqueous sodium hydroxide solution, dilute hydrochloric acid,
5% sodium bicarbonate solution and water each time. The
organic phase was then dried and concentrated. This gave
0.9 g of 2-thiomethylpyrimidine-4-carboxy-(4-fluorophenyl)-
amide (compound S.1.48).
c) 2-Methylsulfonylpyrimidine-4-carboxy-(4-fluorophenyl)amide
50 mg of sodium tungstate were added to a mixture of 0.4 g of
30% hydrogen peroxide and 5 ml of glacial acetic acid, and
the mixture was stirred for 15 min. 0.9 g (3.4 mmol) of
2-thiomethylpyrimidine-4-carboxy-(4-fluorophenyl)amide
dissolved in glacial acetic acid were then added, and the
mixture was stirred at 25~C for 16 hours. On addition of
100 ml of water, the product precipitated in the form of
yellow crystals and was filtered off with suction. This gave
0.6 g of the title compound (mp. 175-178~C, compound Sl.23).
3. 2-Methylsulfonyl-6-chloropyrimidine-4-carboxy-(4-fluoro-
phenyl)amide (compound Sl.43)
a) 2-Thiomethyl-6-chloropyrimidine-4-carbonyl chloride
50 g (0.27 mol) of 2-thiomethyl-6-hydroxypyrimidine-
4-carboxylic acid (cf. J. Org. Chem. 26 (lg61), 2755-61) and
100 ml of phosphorus oxytrichloride were heated under reflux
at 80~C for six hours. The phosphorus oxytrichloride was
distilled off and the product was fractionated at 100-102~C
and 0.5 mbar. Yield: 36.7 g.
40 b) 2-Thiomethyl-6-chloropyrimidine-4-carboxy-(4-fluorophenyl)-
amide
2.4 g (10.8 mmol) of 2-thiomethyl-6-chloropyrimidine-
4-carbonyl chloride and 1.2 g (11.8 mmol) of triethylamine
were dissolved in 50 ml of dichloromethane (puriss.), and
1.2 g (10.8 mmol) of fluoroaniline was added with stirring.
The mixture was stirred for 16 hours and washed with 50 ml
0050/46965 CA 022~7080 1998-12-01
each of 2 N hydrochloric acid, 5% sodium bicarbonate solution
and water, and the organic phase was dried with sodium
sulfate and concentrated. Chromatography over silica gel
(eluent hexane/MTBE = 9/1) gave 1.3 g of 2-thiomethyl-
5-bromopyrimidine-4-carboxy-(4-fluorophenyl)amide
(mp. 116-120~C; compound Sl.34).
c) 2-Methylsulfonyl-6-chloropyrimidine-4-carboxy-(4-fluoro-
phenyl)amide
100 mg of sodium tungstate were added to a mixture of 2.4 g
of 30% hydrogen peroxide and 20 ml of glacial acetic acid,
and the mixture was stirred for 15 min. 0.7 g (2.4 mmol) of
2-thiomethyl-6-chloropyrimidine-4-carboxy-(4-fluorophenyl)-
amide dissolved in glacial acetic acid were then added, andthe mixture was stirred at 25~C for 16 hours. On addition of
100 ml of water, the product precipitated in the form of
yellow crystals and was filtered off with suction. This gave
0.7 g of the title compound (mp. 180-182~C, compound Sl.43).
Table Sl
R3 O
R2 ~ IN-R5
N~N H
S (O) n-Rl
30 No. n Rl R2 R3 R5 Mp. [~C]
Sl.l 2 CH3 H H 3-CF3-phenyl
Sl.2 2 CH3 Cl H CH2CH2CH2CH3
Sl.3 2 CH3 Cl H 2,4-F2-phenyl
Sl.4 2 CH3 H H CH2-CF3
Sl.5 2 CH3 H Br CH (CH3) -4-Me-phenyl
Sl.6 2 CH3 H Br 2,4-F2-phenyl 200-5
Sl.7 2 CH3 H Br 3,5-Cl2-phenyl 195-201
Sl.8 2 CH3 H Br 4-CN-phenyl oil
40 Sl.9 2 CH3 H Br 3-CN-phenyl oil
Sl.10 2 CH3 H Br 4-F-phenyl 169-74
Sl.ll 2 CH3 H Br 3-F-phenyl 163-6
Sl.12 2 CH3 H Br 2-F-phenyl 160-5
45 Sl.13 2 CH3 H Br 3-Me-phenyl 142-50
Sl.14 2 CH3 H Br 4-Me-phenyl 142-5
Sl.15 0 CH3 H H 2,4-F2-phenyl 138-41
0050/46965 CA 022~7080 1998-12-01
29
No. n R1 R2 R3 Rs Mp. [~C]
S1.16 0 CH3 H H 4-CN-phenyl 155-7
S1.17 0 CH3 H H 3-CN-phenyl 148-50
5 S1 18 0 CH3 H H 2-F-phenyl 114-7
S l .1 9 0 CH3 H H 3-Me-phenyl 100-3
S1.20 2 CH3 H H 3,5-Cl2-phenyl oil
S1.21 2 CH3 H H 4-CN-phenyl oil
Sl.22 2 CH3 H H 3-CN-phenyl 195-7
S1.23 2 CH3 H H 4-F-phenyl 175-8
S1.24 2 CH3 H H 3-F-phenyl 183-6
S1.25 2 CH3 H H 2-F-phenyl 188-9
S1.26 2 CH3 H H 3-Me-phenyl 115-20
15 S1.27 2 CH3 H H 4-Me-phenyl 178-81
S1.28 0 CH3 Cl H phenyl 151-5
S1.29 0 CH3 Cl H 3-Me-phenyl 165-70
S1.30 0 CH3 Cl H 2-F-phenyl 141-5
20 S1.31 0 CH3 Cl H 3-CN-phenyl 170-5
S1.32 0 CH3 Cl H 2,4-F2-phenyl 138-41
S1.33 0 CH3 Cl H 4-Me-phenyl 140-5
S1.34 0 CH3 Cl H 4-F-phenyl 115-20
25 S1.35 0 CH3 Cl H 3-F-phenyl 163-6
S1.36 0 CH3 Cl H 3,5-Cl2-phenyl 175-8
S1.37 0 CH3 Cl H 3-CN-phenyl 158-60
S1.38 1 CH3 Cl H 3-F-phenyl oil
S1.39 2 CH3 Cl H phenyl oil
S1.40 2 CH3 Cl H 3-Me-phenyl 189-90
S1.41 2 CH3 Cl H 2-F-phenyl 192-3
S1.42 2 CH3 Cl H 4-Me-phenyl oil
S1.43 2 CH3 Cl H 4-F-phenyl 180-2
35 S1.44 2 CH3 Cl H 3-F-phenyl oil
S1.45 2 CH3 Cl H 3-CN-phenyl oil
S1.46 2 CH3 Cl H 3,5-Cl2-phenyl oil
S1.47 0 CH3 H Br 4-F-phenyl
40 S1-48 0 CH3 H H 4-F-phenyl
Use examples
For the following experimental investigations of the fungicidal
45 activity of the compounds I, an emulsion comprising 10% by weight
of the active compound and 90 % by weight of a mixture of
- 0050/46965 CA 022~7080 1998-12-01
70 % by weight of cyclohexanol,
20 % by weight of Nekanil~ LN (Lutensol~ AP6, wetting agent
having emulsifying and dispersing action, based
on ethoxylated alkylphenols) and
5 10 % by weight of Uniperol~ EL (nonionic emulsifier based on
ethoxylated castor oil)
was used. The desired active compound concentration was set by
dilution of this emulsion with water. The extent of the infection
10 was determined visually.
