CA2257080A1 - Pyrimidine-4-carboxylic acid amides - Google Patents

Abstract

Pyrimidine-4-carboxylic acid amides of formula (I) and their salts, in which R1 is optionally substituted alkyl, aryl; n is 0, 1, or 2; R2 is hydrogen, hydroxy, halogen, alkyl, alkyl halide, alkoxy, alkoxy halide; R3 is hydrogen, hydroxy, halogen, alkyl, alkyl halide, alkoxy, alkoxy halide, where one of the radicals R2 and R3 always stands for hydrogen; Y is oxygen or sulphur; R4 is hydrogen or optionally partially or fully halogenated alkyl, cycloalkyl; R5 is optionally substituted alkyl, cycloalkyl, aryl; and agents containing them and their use as fungicides.

Description

CA 022~7080 1998-12-01 The present invention relates to pyrimidine-4-carboxamides of the S formula I

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

IV V
o Cl ~ ~ N-R5 oxidation l ll ¦ ~ I (n = 1 or 2) N ~ N y 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

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 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 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

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 where for each compound R5 corresponds to one row in Table A.

Table 3 Compounds of the formula I.3 ~ NH - R5 N~,N (I.3) 2~o=~~=O

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

where for each compound R5 corresponds to one row in Table A.

- ~ 0050/46965 CA 022~7080 1998-12-01 Table 5 Compounds of the formula I.5 ~ NH - R5 N~,N (I.5) 0=-=0 where for each compound Rs corresponds to one row in Table A.
Table 6 Compounds of the formula I.6 ~ NH - R5 N~,N (I.6) ~=O

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

where for each compound Rs corresponds to one row in Table A.

Table 8 Compounds of the formula I.8 O
CH3O ~ NH - Rs N~,N (I.8) '-=~

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

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

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 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 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 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 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.

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 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 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 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 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 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.

Claims (4)

We claim:

1. Pyrimidine-4-carboxamides of the formula I

and salts and N-oxides thereof where:
R1 is C1-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, C1-C4-alkoxyalkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C4-alkylthio, C1-C4-alkoxycarbonyl, C3-C7-cycloalkyl, C3-C7-cycloalkenyl, aryl, aryloxy and hetaryl, it being possible for the cyclic radicals in turn to carry one to three of the following substituents: halogen, cyano, C1-C4-alkyl, C1-C4-alkoxyalkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C4-alkylthio, C1-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, C1-C4-alkyl, C1-C4-alkoxyalkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C4-alkylthio, C1-C4-alkoxycarbonyl, aryl, aryloxy and hetaryl, it being possible for the cyclic substituents in turn to carry one or, independently of one another, two or three of the following substituents: halogen, cyano, C1-C4-alkyl, C1-C4-alkoxyalkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C4-alkylthio and C1-C4-alkoxycarbonyl;
n is 0, 1 or 2;
R2 is hydrogen, hydroxyl, halogen, C1-C8-alkyl, C1-C8-haloalkyl, C1-C8-alkoxy, C1-C8-haloalkoxy;

R3 is hydrogen, hydroxyl, halogen, C1-C8-alkyl, C1-C8-haloalkyl, C1-C8-alkoxy, C1-C8-haloalkoxy;

one of the radicals R2 and R3 in each case always being hydrogen;
Y is oxygen or sulfur;

R4 is hydrogen or C1-C8-alkyl which may be partially or fully halogenated or C3-C7-cycloalkyl which may be partially or fully halogenated;

R5 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, C1-C4-alkyl, C1-C4-haloalkyl and C1-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, C1-C4-alkyl, C1-C4-alkoxyalkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C4-alkylthio, C1-C4-alkoxycarbonyl, where the C1-C4-alkoxycarbonyl radical is not in the ortho position, aryl, aryloxy and hetaryl, it being possible for the cyclic substituents in turn to carry one or, independently of one another, two or three of the following substituents: halogen, cyano, C1-C4-alkyl, C1-C4-alkoxyalkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C4-alkylthio and C1-C4-alkoxycarbonyl.

2. Fungicides, comprising a fungicidally active amount of a compound of the formula I or a salt or N-oxide thereof as claimed in claim 1 and at least one conventional formulation auxiliary.

3. A method for controlling harmful fungi, which comprises treating the harmful fungi, their habitat or the plants, areas, materials or spaces to be kept free from them with an active amount of a compound of the general formula I or a salt or N-oxide thereof as claimed in claim 1 or a fungicide as claimed in claim 2.

4. The use of the compounds of the general formula I and of salts and N-oxides thereof as claimed in claim 1 for controlling harmful fungi.