WO2006136327A1

WO2006136327A1 - Fungicidal benzylpyrimidine derivatives

Info

Publication number: WO2006136327A1
Application number: PCT/EP2006/005780
Authority: WO
Inventors: Mamoru Hatazawa; Masahito Ito; Yasuo Araki; Tetsuya Inuta
Original assignee: Bayer Cropscience Ag
Priority date: 2005-06-21
Filing date: 2006-06-16
Publication date: 2006-12-28
Also published as: JP2007031424A; TW200745054A; AR054791A1

Abstract

Novel benzylpyrimidine derivatives of the formula (I) wherein, R represents C2-6 alkyl, X represents halogen, Y represents halogen, and n is an integer of 0 to 2, when n is 2 the two Y radicals may be the same or different from each other, and the use of the new compounds as fungicides.

Description

FUNGICIDAL BENZYLPYRIMIDINE DERIVATIVES

The present invention relates to novel benzylpyrimidine derivatives, to their use as fungicides and to processes for their preparation.

It has been known that specific pyrimidine derivatives function as a fungicide, for example, see Japanese Patent Application Laid-Open No. 8-283246 (hereinafter referred to as JP-8-283246A), German Patent No. 4029649, WO02/74753, WO03/43993, German Patent No. 4034762, and European Patent No. 407899.

Moreover, it has been known that specific pyrimidine derivatives have various biological activities, for example, see WO 99/19305 in which a function to the central nervous system is disclosed, and WO00/61562 in which function to the nervous system is disclosed.

There have now been found novel benzylpyrimidine derivatives of the formula (I)

wherein,

R represents C₂-₆ alkyl,

X represents halogen,

Y represents halogen, when n is 2 the two Y radicals may be the same or different each other, and

n is an integer of 0 to 2.

The compound of formula (I), according to the present invention, can be obtained by a process

a)

NTP 835 + 835.01 compounds of the formula (II)

wherein X, Y and n have the same definition as aforementioned are reacted, with^' compounds of the formula (III)

R-NH₂ (III)

wherein R has the same definition as aforementioned,

in the presence of inert solvents, and if appropriate, in the presence of an acid binder.

The benzylpyrimidine derivatives of the formula (I) which are provided by the present invention show a strong fungicidal action.

The benzylpyrimidine derivatives of the formula (I), according to the present invention, are novel compounds that have not specifically been disclosed in the above-mentioned JP-8-283246A, although the benzylpyrimidine derivatives of the present invention are generically embraced by the general formula disclosed in JP-8-283246A. Moreover, unexpectedly, the compounds of the formula (I), according to the present invention, exert substantially superior preventive function against plant diseases in comparison with the known compounds having analogous structures and specifically described in JP-8-283246A. Particularly, the compounds of the formula (I) have a remarkably superior preventive function against plant diseases, such as Phytophthora infestans, Sphaerotheca fuliginea, Alternariamali, Pyriculaia oryzae, Gibberella ficjikuroi and Cochliobolus miyabeanus . Phakopsora pachyrhizi and so on.

Therefore, the benzylpyrimidine derivatives of the formula (I), according to the present invention, are very useful as fungicides for agriculture and horticulture.

In the present specification, "halogen" indicates fluorine, chlorine, bromine or iodine, and, preferably, is fluorine or chlorine.

"C₂.6 alkyl" may be linear or branched, and is for example, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 1 ,2-dimethylpropyl, neo-pentyl, 1 -ethylpropyl, iso-pentyl, 1,2,2-trimethylpropyl or 1,3-dimethylbutyl. Among the compounds of the formula (I), those are preferable wherein

R represents ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 1 ,2-dimethylpropyl, neo-pentyl, 1 -ethylpropyl, iso-pentyl, 1 ,2,2-trimethylpropyl or 1 ,3-dimethylbutyl,

X represents fluorine, chlorine, bromine or iodine,

Y represents fluorine or chlorine, when n is 2 the two Y radicals may be the same or different from each other, and

n is an integer of 0 to 2.

Among the compounds of the formula (I), those are more preferable wherein

R represents isopropyl, isobutyl, sec-butyl or neo-pentyl,

X represents fluorine, chlorine or bromine,

Y represents fluorine or chlorine, and

n is an integer of 0 to 2,

when n is 1 the Y is bonded to the 4- or 5-position of the phenyl moiety, and when n is 2 the two Y radicals are bonded to the 4- and 5-positions of the phenyl moiety and they may be the same or different from each other.

When the group of R contains an asymmetric carbon atom, the compounds of the formula (I) include enantiomers (R/S configuration).

The preparation method (a) mentioned above may be specifically represented by the following reaction formula when, for example, 4,6-dichloro-5-(3-chlorobenzyl)pyrimidine and isopropyl amine are used as the starting materials

In the preparation method (a), the compounds of the formula (II), which are used as the starting materials, are in part novel compounds that have not been described in prior art documents, and can be easily prepared by reacting compounds of the formula (FV)

wherein X, Y and n have the same definition as aforementioned,

with a halogenating agent such as phosphorus oxychloride in accordance with the methods described, for example, in Journal of Heterocyclic Chemistry, Vol. 29, pp. 1369-1370, 1992, Journal of Organic Chemistry, Vol. 32, No. 2, pp. 1591-1596, 1967, and Journal of Medicinal Chemistry, Vol. 45, No. 17, pp. 3639-3648, 2002.

The compounds of the formula (FV) are in part novel compounds that have not been described in prior art documents, and can be easily prepared by reacting compounds of the formula (V)

wherein,

» R¹ represents Ci_-4 alkyl, and

X, Y and n have' the same definition as aforementioned,

with formamidine acetate or formamidine hydrochloride in accordance with the methods described, for example, in Journal of the American Chemical Society, Vol. 77, pp. 745-749, 1955, Journal of the American Chemical Society, Vol. 69, pp. 2941-2942, 1938, and Journal of Medicinal Chemistry, Vol. 45, No. 17, pp. 3639-3648, 2002.

The compounds of the formula (V) are in part novel compounds which have not been described in prior art documents, and can be easily prepared by reacting compounds of the formula (VI)

wherein R¹ has the same definition as aforementioned,

with compounds of the formula (VII)

wherein,

X¹ represents halogen, preferably, chloro, bromo or iodo, and

X and Y have the same definition as aforementioned,

in accordance with the methods described, for example, in Japanese Patent Application Laid-Open No. 11-228500, and Journal of Medicinal Chemistry, Vol. 45, No. 17, pp. 3639-3648, 2002.

The compounds of the above formulae (VI) and (VlI) per se are known compounds.

The compounds of the formula (III) pre se which are used as the starting materials in the preparation method (a) are known compounds.

Specific examples of the compounds of the formula (II) which are used as the starting materials in the preparation method (a) include the followings:

4,6-dichIoro-5-(3-fluorobenzyl)pyrimidine,

4,6-dichloro-5-(3-chlorobenzyl)pyrimidine,

4,6-dichloro-5-(3-bromobenzyl)pyrimidine,

4,6-dichloro-5-(3-iodobenzyl)pyrimidine,

4,6-dichloro-5-(3,4-difluorobenzyl)pyrimidine,

4,6-dichloro-5-(2,5-difluorobenzyl)pyrimidine, 4,6-dichloro-5-(3,5-difluorobenzyl)pyrimidine,

4,6-dichIoro-5-(3,5-dichlorobenzyl)pyrimidine and

4,6-dichloro-5-(3,4,5-trifluorobenzyl)pyrimidine, and so on.

Specific examples of the compounds of the formula (FV) which are used as the starting materials in the preparation of the compounds of the above formula (II) include the followings;

4,6-dihydroxy-5-(3-fluorobenzyl)pyrimidine,

4,6-dihydroxy-5-(3-chlorobenzyl)pyrimidine,

4,6-dihydroxy-5-(3-bromobenzyl)pyrimidine,

4,6-dihydroxy-5-(3-iodobenzyl)pyrimidine,

4,6-dihydroxy-5-(3,4-difluorobenzyl)pyrimidine,

4,6-dihydroxy-5-(2,5-difluorobenzyl)pyrimidine,

4,6-dihydroxy-5-(3,5-difluorobenzyl)pyrimidine,

4,6-dihydroxy-5-(3,5-dichlorobenzyl)pyrimidine and

4,6-dihydroxy-5-(3,4,5-trifluorobenzyl)pyrimidine, and so on.

Specific examples of the compounds of the formula (V) which are used as the starting material in the preparation of the compounds of the above formula (FV) include the followings:

diethyl (3-fluorobenzyl)malonate,

diethyl (3-chlorobenzyl)malonate,

diethyl (3-bromobenzyl)maIonate,

diethyl (3 -iodobenzyl)malonate,

diethyl (3 ,4-difluorobenzyl)malonate,

diethyl (2,5-difluorobenzyl)malonate,

diethyl (3,5-difluorobenzyl)malonate, diethyl (3,5-dichlorobenzyl)malonate and

diethyl (3,4,5-trifluorobenzyl)malonate, and so on.

Specific examples of the compounds of the formula (VI) which are used as the starting materials in the preparation of the compounds of the above formula (V) include diethyl malonate and dimethyl malonate.

Specific examples of the compounds of the formula (VII) which are used as the starting materials in the preparation of the compounds of the above formula (V) include the followings:

3-fluorobenzylbromide,

3-chlorobenzylbromide,

3-bromobenzylbromide,

3-iodobenzylbromide,

3 ,4-difluorobenzylbromide,

2,5-difluorobenzylbromide,

3,5-difluorobenzylbromide,

3,5-dichlorobenzylbromide and

3,4,5-trifluorobenzylbromide, and so on.

Specific examples of the compounds of the formula (III) which are used as the starting materials in the preparation method (a) include the followings:

ethylamine,

n-propylamine,

iso-propylamine,

n-butylamine,

iso-butylamine,

sec-butylamine, (R)-sec-butylam ine,

(S)-sec-butylamine,

tert-butylamine,

n-amylamine,

iso-amylamine,

1 -ethylpropylamine,

3-methyl-2-butylamine,

(R)-3 -methyl-2-buty lam ine,

(S)-3-methyl-2-butylamine,

2,2-dimethylpropylamine and

1,3-dimethylbutylamine, and so on.

The reaction of the above preparation method (a) may be carried out in an appropriate diluent, and examples thereof include:

aliphatic, alicyclic and aromatic hydrocarbons, which optionally may be chlorinated, such as pentane, hexaηe, cyclohexane, petroleum ether, ligroin, benzene, toluene, xylene,

dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, chlorobenzene and dichlorobenzene;

ethers, such as ethyl ether, methyl ethyl ether, isopropyl ether, and butyl ether,

dioxane, dimethoxyethane (DME), tetrahydrofuran (THF), diethyleneglycol and dimethyl ether (DGM);

ketones, such as acetone, methyl ethyl ketone (MEK), methyl-isopropyl ketone and methyl isobutyl ketone (MDBK);

nitriles, such as acetonitrile, propionitrile and

acrylonitrile; alcohols, such as methanol, ethanol, isopropanol, butanol and ethyleneglycol;

esters, such as ethyl acetate and amyl acetate;

acid amides, such as dimethylformamide (DMF), dimethylacetamide (DMA), N-methylpyrrolidone, l,3-dimethyl-2-imidazolidinone and hexamethylphosphoric triamide (HMPA);

sulfones and sulfoxides, such as dimethylsulfoxide (DMSO) and sulforane; and

bases, such as pyridine.

The preparation method (a) can be carried out in the presence of an acid binder, and examples thereof include inorganic bases, such as hydrides, hydroxides, carbonates and bicarbonates of alkali metals and alkali earth metals, and specific examples thereof include:

sodium hydride, lithium hydride,

sodium hydrogencarbonate, potassium hydrogencarbonate, sodium carbonate, potassium carbonate,

lithium hydroxide, sodium hydroxide, potassium hydroxide and calcium hydroxide;

inorganic alkali metal amides, such as lithium amide, sodium amide and potassium amide;

organic bases, such as alcoholate, tertiary amines, dialkylaminoanilines and pyridines, e.g., triethylamine, 1,1,4,4-tetramethylethylenediamine (TMEDA), N,N-dimethylaniline, N,N-diethylaniline,

pyridine, 4-dimethylaminopyridine (DMAP), l,4-diazabicyclo[2,2,2]octane (DABCO) and 1 ,8-diazabicyclo[5,4,0]undec-7-ene (DBU);

organic amine hydrochlorides, such as pyridine hydrochloride and triethylamine hydrochloride; and

amine sulfonates, such as pyridine p-toluenesulfonate and triethylamine p-toluenesulfonate,.

The preparation method (a) can be carried out in a substantially wide temperature range.

The temperature range is generally set from about -78 to about 200⁰C, more preferably, from about -20 to about 180⁰C.

Moreover, the reaction is preferably carried out under normal pressure, although it may be carried out under a high or reduced pressure.

The preparation method (a) may be carried out, for example, by reacting 1 mole of the compounds of the formula (II) with 1.0 mole to 10.0 moles of the compounds of the formula (III) in a diluent such as tetrahydrofuran in the presence of triethylamine thereby to obtain the aimed compounds of the formula (I).

The active compounds of the formula (I), according to the present invention, which show a strong fungicidal function, can be practically used for eliminating undesirable pathogenic fungi against plants.

In general, the active compounds of the formula (I),according to the present invention, may be used, as fungicides, against various diseases of plants suffering from Plasmodiophoromycetes, Oomycetes, Zygomycetes, Ascomycetes, Basidiomycetes and Deuteromycetes .

According to the present invention, the active compounds of the formula (I) particularly show superior preventive effects on pathogenic fungi against plants, such as:

Phytophthora infestans,

Sphaerotheca fuliginea,

Alternaria mali,

Gibberella fujikuroi,

Pyriculaia oryzae,

CocMiobolus miyabeanus,

Phakopsora pachyrhizi and so on.

The active compounds of the formula (I), according to the present invention, have good compatibility to plant bodies in a concentration thereof required for preventing pathogenic fungi against plants. The active compounds of the present invention may be used for treating plant bodies above the ground, treating the rootstock or seeds, and treating the soil.

Moreover, the active compounds of the formula (I), according to the present invention, have low toxicity on warm-blooded animals, and thus may be used safely.

When used as agrichemicals, the active compounds of formula (I) , according to the present invention can be converted into the conventional formulation forms. Examples of the formulation forms include solutions, wettable powders, emulsions, suspensions, powders, dusts, pastes, tablets, granules, aerosols, active-compound impregnated-natural and synthetic materials, microcapsules, coatings for seeds and ULV (cold mist and warm mist).

These formulations can be produced in a manner known per se, for example, by mixing the active compound with an extruder, that is, liquid diluents, solid diluents, or carriers, optionally with the use of a surfactant, that is, emulsifiers and/or dispersants and/or foam-formers.

5 The liquid diluents or carriers generally include aromatic hydrocarbons (e.g., xylene, toluene and alkylnaphthalene), chlorinated aromatic or chlorinated aliphatic hydrocarbons (e.g., chlorobenzenes, ethylene chlorides and methylene chlorides), aliphatic hydrocarbons [e.g., cyclohexane and paraffins (e.g., mineral oil fraction)], alcohols (e.g., butanol and glycol) and ethers, esters, ketones (e.g., acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone), strongly polar ,10 solvents (e.g., dimethylformamide and dimethylsulfoxide) and water. When the extruder used is water, for example, an organic solvent may be used as an auxiliary solvent.

The solid diluents include, for example, ground natural minerals (e.g., kaolin, clay, talc, chalk, quartz, attapulgite, montmorillonite and diatomaceous earth) and ground synthetic minerals (e.g., highly-dispersed silica, and alumina and silicate).

15 The solid carriers for granules include, for example, crushed and fractionated natural rocks (e.g., calcite, marble, pumice, sepiolite and dolomite), synthetic granules of inorganic or organic meals and granules of organic material (e.g., sawdust, coconut shells, maize cobs and tobacco stalks).

The emulsifiers and/or foam-formers include, for example, nonionic and anionic emulsifiers [e.g., polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers (e.g., alkylaryl polyglycol 20 ethers, alkylsuifonates, alkyl sulfates and arylsulfonates)] and albumin hydrolysates.

The dispersants.include, for example, lignosulfite waste liquors and methylcellulose.

Tackifiers may also be used in the formulation (in the form of powders, granules, or emulsions), which include carboxymethylcellulose, natural and synthetic polymers (e.g., gum arabic, polyvinyl alcohol, and polyvinyl acetate).

25 Colorants may also be used, which include inorganic pigments (e.g., iron oxide, titanium oxide and

Persian Blue), and organic dyes such as alizarin dyestuffs, azo dyestuffs or metal phthalocyanine . dyestuffs, as well as trace nutrient metals such as iron, manganese, boron, copper, cobalt, molybdenum and zinc and salts thereof.

The formulations generally contain the active compound represented by formula (I) of the present

30 invention at a rate within a range of 0.1 to 95% by weight, more preferably, in a range of 0.5 to

90% by weight. The active compounds of the formula (I) , according to the present invention, can be used in the above formulations and in various use forms as a mixture with other known active compounds, such as fungicides (fungicides, bactericides), insecticides, acaricides, nematicides, herbicides, bird repellents, growth-regulating agents, fertilizers and/or soil conditioners.

In the practical use of the active compounds of the formula (I) , according to the present invention, it may be directly used as it is, or may be used in various use forms, such as prepared solutions for spraying, emulsions, suspensions, powders, tablets, pastes, microcapsules and granules, or may be used in a further diluted and adjusted form. Moreover, the active compounds may be applied by conventional methods, such as watering, soaking, spraying, atomizing, misting, irrigation, suspension-forming, coating, dusting, scattering, dressing, wet-dressing, wet-coating, paste-coating and plumage-coating.

The concentration of the active compound in practical use forms to treat respective portions of a plant body may vary within a practical range, and is generally set in a range of 0.0001 to 1% by weight, preferably, in a range of 0.001 to 0.5% by weight.

For the treatments on seeds, the active compound may be generally used at a rate within a range of 0.001 to 50 g, preferably, within a range of 0.01 to 1O g, per kg of the seeds.

For the soil treatment, the active compound may be generally used at a concentration, with respect to the site of action, within a range of 0.00001 to 0.1% by weight, particularly, within a range of 0.0001 to 0.02% by weight.

The following description will further describe the preparation and use of the compounds of the present invention more specifically through the following examples, however, the present invention is not intended to be limited only to these examples.

Synthesis Example 1

To tetrahydrofuran (20 ml) was added and dissolved 4,6-dichloro-5-(3,5-difluorobenzyl)pyrimidine (160 mg, 0.58 mmol), and to the mixture was further added isopropylamine (210 μl, 2.4 mmol) and triethylamine (170 μl, 1.2 mmol). After heating the mixture under reflux for 7 hours, isopropyl amine (420 μl, 4.8 mmol) was added to the mixture and refluxed under heat for 5 hours. Upon the completion of the reaction, the precipitate was removed, and the filtrate was condensed in vacuo. The residue was purified with a silica gel column chromatography (elution solvent: n-hexane/ethyl acetate = 9/1) to obtain 5-(3,5-difluorobenzyl)-4-chloro-6-isopropyl- aminopyrimidine (150 mg, yield: 88%).

mp 119-121⁰C.

Synthesis Example 2

To tetrahydrofuran (20 ml) was added and dissolved 4,6-dichloro-5-(3,5-difluorobenzyl)pyrimidine (170 mg, 0.6 mmol), and to the mixture was further added isobutyl amine (240 μl, 2.4 mmol) and triethyl amine (250 μl, 1.8 mmol), and the mixture was refluxed under heat for 7 hours. Upon the completion of the reaction, the precipitate was removed, and the filtrate was condensed in vacuo. The residue was purified with a silica gel column chromatography (elution solvent: n-hexane/ethyl acetate = 9/1) to obtain 5-(3,5-difluorobenzyl)-4-chloro-6-isobutylaminopyrimidine (180 mg, yield: 97%).

mp 82-83°C.

Synthesis Example 3

To tetrahydrofuran (4 ml) and ethanol (500 μl) was added and dissolved 4,6-dichloro-5-(3-chlorobenzyl)pyrimidine (273 mg, 1.0 mmol), and to the mixture was further added isopropylamine (260 μl, 3.0 mmol) and triethylamine (420 μl, 3.0 mmol), and the resulting mixture was allowed to react at 180°C for 25 minutes by using a microwave reactor (Initiator™, produced by Biotage). Upon the completion of the reaction, the precipitate was removed, and the filtrate was condensed in vacuo. The residue was purified with a silica gel column chromatography (elution solvent: n-hexane/ethyl acetate = 9/1 ) to obtain

5-(3-chlorobenzyl)-4-chloro-6-isopropylaminopyrimidine (261 mg, yield: 88%).

mp l l O-1 12°C.

The compounds of the formula (I) obtained by the same manner as the above Synthesis Examples 1 to 3, are shown in Table 1 together with the compounds that have been synthesized by Synthesis Examples 1 to 3.

Table 1

Reference Example 1 (Preparation of Intermediate)

To acetone (300 ml) were suspended 3-fluorobenzyl bromide (50 g, 0.26 mol), diethyl malonate (320 ml, 2.1 mol) and potassium carbonate (80 g, 0.58 mol), and the mixture was stirred at 75°C for 6 hours. Upon the completion of the reaction, the precipitate was filtered, and washed with acetone. The solvent and excess diethyl malonate were removed in vacuo, and residue was purified with a silica gel column chromatography (elution solvent: n-hexane/ethyl acetate = 20/1) to obtain diethyl(3-fluorobenzyl) malonate (62 g). Reference Example 2 (Preparation of Intermediate)

To a suspension of formamidine acetate (11.5 g, 0.11 mol) and ethanol (200 ml) was added a solution of sodium methoxide in 28% methanol (58 g, 0.3 mol) under ice-cooling, and the mixture was stirred for 20 minutes successively under ice-cooling. To the mixture was added diethyl(3-fluorobenzyl) malonate (26.8 g, 0.1 mol). The mixture was stirred for 30 minutes successively under ice-cooling, stirred at room temperature for 15 hours, and then refluxed under heat for 15 hours. Ethanol was removed therefrom in vacuo, and water was added thereto. To the mixture was added cone, hydrochloric acid (30 g) under ice-cooling, and the resulting precipitate was filtered. The filtrate was washed with water and then n-hexane, and dried in a desiccator to obtain 4,6-dihydroxy-5-(3-fluorobenzyl)pyrimidine (21 g).

The product thus obtained was used in the next reaction without further purification.

Reference Example 3 (Preparation of Intermediate)

To 4,6-dihydroxy-5-(3-fluorobenzyl)pyrimidine (21 g) were added N,N-dimethyl aniline (25 ml) and phosphorus oxychloride (150 ml), and the mixture was refluxed under heat for 10 hours. Upon the completion of the reaction, excessive phosphorus oxychloride was removed in vacuo, ice water was added, and extracted with ethyl acetate. The ethyl acetate layer was dried with anhydrous magnesium sulfate, and filtered through a glass filter charged with silica gel ^y usimj ethyl acetate. The crude product obtained by condensing the filtrate in vacuo was dissolved in ethanol, and ice water was added. The resulting precipitate was filtered, washed with water, and then dried in a desiccator to obtain 4,6-dichloro-5-(3-fluorobenzyl)pyrimidine (22.7 g).

mp 47-49°C.

By using the similar processes as the above Reference Examples 1 to 3, the following compounds are obtained as typical examples: ,6-dichloro-5-(2,5-difluorobenzyl)pyrimidine, mp 115-117⁰C;

,6-dichIoro-5-(3,4-difluorobenzyl)pyrimidine, mp 61-69⁰C;

,6-dichloro-5-(3,4,5-trifluorobenzyl)pyrimidine, n_D ²⁰ 1.4750; and

,6-dichloro-5-(3,5-dichlorobenzyl)pyrimidine; mp 109-1 10⁰C.

Comparative compounds

(Comparative compounds C-I to C-5 are analogues compounds to the present compounds and are disclosed in JP-8-283246A.)

Biological Test Example 1 : Efficacy test against Phytophthora infestans by spraying the samples to stalks and leaves

Preparation of sample compounds

Active compound: 5 parts by weight

Organic solvent: Acetone 142.5 parts by weight

Emulsifier: Polyoxyethylene alkylphenyl ether 7.5 parts by weight The above active compound, acetone and emulsifier were mixed, and diluted with water to a predetermined concentration to prepare a sample compound.

Test Method

Tomato (cultivar: Regina) was grown in a plastic pot of 4 cm in diameter, and to the small seedling 5 that had grown to have 2 to 3 leaves was sprayed a diluent of the active compound having a predetermined concentration preliminarily prepared, at an amount of 6 ml per three pots. One day after the spraying, zoosporangia, formed on disease spots of Phytophthora infestans that had been previously infected to tomatoes and developed thereon, were washed off with a brush into distilled water to prepare a suspended solution. This suspended solution was atomized over the treated ,10 plants as an inoculation source so as to be inoculated (once), and the resulting plants were maintained at 2O⁰C and a relative humidity of 100% to allow the infection. Four days after the inoculation, the morbidity per pot was classified and evaluated, and the preventive value (%) was determined. Moreover, the phytotoxicity was simultaneously examined. The present tests were carried out based upon the average of the results of one section including three pots.

15 The evaluation on the morbidity and the calculations of the preventive value (%) were carried out in the following criteria:

Morbidity Rate of disease spot area (%)

0.5 less than 2

20 1 2 to less than 5

2 5 to less than 10

3 10 to less than 20

4 20 to less than 40

5 40 or more

25

Preventive value (%) = [1 - (Morbidity of treated section / Morbidity of non-treated section)] x 100 The test results on Compound Nos. 1-5, 1-10, 1-14, 1-17, 1-22, 1-25, 1 -27, 1 -31 , 1-42, 1-44 and 1-47 as well as on Comparative compounds C-I , C-2, C-3, C-4 and C-5 are shown in the following Table 2 as specific examples. Here, no phytotoxicity was found with the compounds of the present invention.

Table 2: Preventive value (%) to Phytophthora infestans

Biological Test Example 2: Efficacy test against Sphaerotheca fuliginea by spraying the samples to stalks and leaves Test Method

Cucumber (cultivar: Sagamihanpaku) was grown in a plastic pot of 4 cm in diameter, and to the small seedling that had grown to cotyledons was sprayed a diluent of the active compound having a predetermined concentration preliminarily prepared in the same manner as in Test Example 1 , at an amount of 6 ml per three pots. One day after the spraying, spores of Sphaerotheca fuliginea that had been previously infected to cucumbers and developed thereon were washed off into distilled water to prepare a suspended solution. This suspended solution was atomized over the treated plants as an inoculation source so as to be inoculated (once), and the resulting plants were kept in a green house to allow the infection. Seven days after the inoculation, the morbidity per pot was classified and evaluated, and the preventive value (%) was determined. Moreover, the phytotoxicity was simultaneously examined. The present tests were carried out based upon the average of the results of one section including three pots.

The evaluation on the morbidity and the calculations of the preventive value (%) were carried out in the following criteria:

Morbidity Rate of disease spot area (%)

0.5 less than 2

1 2 to less than 5

2 5 to less than 10

3 10 to less than 20

4 20 to less than 40

5 40 or more

Preventive value (%) = [1 - (Morbidity of treated section / Morbidity of non-treated section)] x 100

The test results on Compound Nos. 1-5, 1-6, 1-7, 1-9, 1-12 and 1-42 as well as on Comparative compounds C-I, C-2, C-3, C-4 and C-5 are shown in the following Table 3 as specific examples. Here, no phytotoxicity was found with the compounds of the present invention. Table 3: Preventive value (%) to Sphaerotheca fuliginea

Biological Teist Example 3: Efficacy test against Pyriculaia oryzae by spraying the samples to stalks and leaves

Test Method

Paddy-field rice (cultivar: Koshihikari) was grown in a plastic pot of 4 cm in diameter, and to the small seedling that had grown to have 1.5 to 2 leaves was sprayed a diluent of the active cόmpourfd having a predetermined concentration preliminarily prepared in the same manner as Test Example 1 , at an amount of 6 ml per three pots. One day after the spraying, a suspension of spores of Pyriculaia oryzae that had been artificially cultivated was atomized over the treated plants so as to be inoculated (once), and the resulting plants were maintained at 25°C and a relative humidity of 100% to allow the infection. Seven days after the inoculation, the morbidity per pot was classified and evaluated, and the preventive value (%) was determined. Moreover, the phytotoxicity was simultaneously examined. The present tests were carried out based upon the average of the results of one section including three pots. The evaluation on the morbidity and the calculations of the preventive value (%) were carried out in the following criteria:

Morbidity Rate of disease spot area (%)

0 0

0.5 less than 2

1 2 to less than 5

2 5 to less than 10

3 10 to less than 20

4 20 to less than 40

5 40 or more

The test results of Compound Nos. 1-3, 1-4, 1-5, 1 -6, 1-7, 1-9, 1-10, 1-12, 1-13, 1-14, 1-16, 1 -18, 1-19, 1-21, 1-22, 1-24, 1-26, 1-27, 1-28, 1-29, 1-31, 1-38, 1-39, 1-40, 1-42, 1-43, 1-46, 1-47, 1-49, 1-52, 1-54 and 1 -56 as well as on Comparative compounds C-I, C-2, C-3, C-4 and C-5 are shown in the following Table 4 as specific examples. Here, no phytotoxicity was found in the compounds of the present invention.

Table 4: Preventive value to Pyriculaia oryzae

Biological Test Example 4: Efficacy test against Phakopsora pachyrhizi by spraying the samples to stalks and leaves

Test method

Soybean (variety: Miyagishirome) was cultivated in a plastic pot of 7.5cm in diameter. To the seedlings which had reached at 1.5 leaf stage, 6 ml of the test chemical solution per 3 pots, which had been prepared in the same manner as Test Example 1, was sprayed. One day after spraying, the leaves were inoculated with a urediniospore suspension (1 x 105 urediniospores/ml) of the pathogen (Phakopsora pachyrhizi) by using a spray gun. 14 days after the inoculation, the severity per pot was evaluated and the protective value was calculated. Phytotoxicity was observed -at the same-time. , f

Morbidity Rate of disease spot area (%)

0 0

0.5 less than 2

1 2 to less than 5

2 5 to less than 10

3 10 to less than 20

20 to less than 40 40 or more

Test result

Compound Nos. 1-5, 1-6, 1-7, 1-9, 1-11, 1-12, 1-21, 1-27, 1-35, 1-36, 1-39, 1-4?,^' 1-43, 1-46, 1-49, 1-51, 1-57 and 1-58 showed, as typical examples, more than 80% of a preventive value in an agent concentration of 500 ppm. Here, no phytotoxicity was found in the compounds of the present invention.

Formulation Example 1 (granules)

Water (25 parts) was added to a mixture of Compound No. 1 -12 (10 parts) of the present invention, bentonite (montmorillonite)(30 parts), talc (58 parts) and lignosulfite (2 parts), and the mixture was kneaded sufficiently and made into grains of 10 to 40 meshes by using an extrusion-type granulator, and then dried at a temperature in a range of 40 to 50⁰C to prepare granules.

Formulation Example 2 (granules)

Clay mineral grains (95 parts) having a grain-size distribution of 0.2 to 2 mm was charged into a rotary mixer, and Compound No. 1-47 (5 parts) of the present invention mixed in a liquid diluent was atomized under rotation so as to be uniformly moistened, and the resulting grains were dried at a temperature in a range of 40 to 50⁰C to prepare granules.

Formulation Example 3 (emulsifiable concentrate)

Compound No. 1-18 (30 parts) of the present invention, xylene (55 parts), polyoxyethylene alkylphenyl ether (8 parts) and alkylbenzene calcium sulfonate (7 parts) were mixed and stirred to prepare an emulsion.

Formulation Example 4 (wettable powders)

Compound No. 1-5 (15 parts) of the present invention, a mixture of white carbon (hydrous non-crystallized silicon oxide fine powder) and powdered clay (l :5)(8O parts), alkylbenzene sodium sulfonate (2 parts) and polymer sodium alkylnaphthalene-sulfonate-formalin (3 parts) were powder-mixed to prepare wettable powders.

Formulation Example 5 (wettable powders)

Compound No. 1-42 (20 parts) of the present invention, sodium lignosulfonate (30 parts), bentonite (15 parts) and calcined diatomaceous earth powder (35 parts) were mixed sufficiently, and water was added thereto, and the resulting mixture was extruded through a screen of 0.3 mm anci dried to prepare water-dispersible granules.

Claims

CLAIMES

1) Novel benzylpyrimidine derivatives of the following formula (I)

wherein,

R represents C_2-6 alkyl;

X represents halogen;

Y represents halogen, when n is 2 the two Y radicals may be the same or, different from each other; and

n is an integer of 0 to 2.

2) The compounds set forth in Claim 1, wherein, t R represents ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl,

1,2-dimethylpropyl, neo-pentyl, 1 -ethylpropyl, iso-pentyl, 1,2,2-trimethylpropyl or 1,3-dimethylbutyl;

X represents fluorine, chlorine, bromine or iodine;

/ >

Y represents fluorine or chlorine, when n is 2 the two Y radicals may be the same or different from each other; and

n is an integer of 0 to 2.

3) The compounds set forth in Claim 1 , wherein

R represents isopropyl, isobutyl, sec-butyl or neo-pentyl; X represents fluorine, chlorine or bromine;

Y represents fluorine or chlorine; and

n is an integer of 0 to 2;

4) A process for the preparation of the compounds of the formula (I)

wherein,

R represents C₂^ alkyl;

X represents halogen;

Y represents halogen, when n is 2 the two Y radicals may be the same or different from each other; and

n is an integer of 0 to 2,

characterized in that

a)

compounds of the formula (II)

wherein X, Y and n have the same definition as aforementioned are reacted, with compounds of the formula (III)

R-NH₂ (III)

wherein R has the same definition as aforementioned,

5) Fungicidal compounds, characterized in that they contain at least one benzylpyrimidine derivative of the formula (I) according to Claim 1.

6) Process for combating undesired fungi, characterized in that benzylpyrimidine derivatives of the formula (I) according to Claim 1 are applied to the microorganisms and / or to their habitat.

7) Use of benzylpyrimidine derivatives of the formula (I) according to Claim 1 for combating undesired fungi.

8) ^" Process^ for the preparation of fungicidal compositions, characterized in that benzylpyrimidine derivatives of the formula (I) according to Claim 1 are mixed with extends and / or surface active agents.