JP2007031424A - Benzylpyrimidine derivative and fungicide for agriculture and horticulture - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a benzylpyrimidine derivative exhibiting excellent activity as a fungicide for agriculture and horticulture. <P>SOLUTION: The benzylpyrimidine derivative is represented by formula (wherein R is a 2-6C alkyl; X is a halogen; Ys are each a halogen and when n is 2, two Ys may each be same or different and n is an integer of 0-2) and utilized as the fungicide for agriculture and horticulture. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a novel benzylpyrimidine derivative and its use as an agricultural and horticultural fungicide.

It is already known that certain pyrimidine derivatives exhibit an action as a fungicide (see, for example, Patent Documents 1 to 6).
Moreover, it is known that a certain kind of pyrimidine derivative has various physiological activities (for example, refer patent documents 7-8).
JP-A-8-283246, German Patent No. 4029649, PCT International Publication WO02 / 74753 pamphlet, PCT International Publication WO 03/43993 Pamphlet, German Patent No. 4034662, European Patent No. 407899, PCT International Publication WO 99/19305 Brochure: Action on the central nervous system, PCT International Publication WO 00/61562 pamphlet: action on nervous system,

  As a result of intensive studies to create a novel useful compound having a higher effect as an agricultural and horticultural fungicide, the present inventors have developed a novel compound represented by the following formula (I) having excellent biological activity. Benzylpyrimidine derivatives were found.

式中、
ＲはＣ_２−６アルキルを示し、
Ｘはハロゲンを示し、
Ｙはハロゲンを示し、ｎが２を示す場合、２個のＹはそれぞれ同一又は相異なっていてもよく、そして
ｎは０〜２の整数を示す。

Where
R represents C _2-6 alkyl;
X represents halogen,
Y represents halogen, and when n represents 2, two Ys may be the same or different from each other, and n represents an integer of 0 to 2.

  The compound of the formula (I) of the present invention can be synthesized, for example, by the following production method (a).

Manufacturing method (a)
formula

式中、
Ｘ、Ｙ及びｎは前記と同義である、
で表される化合物を
式
Ｒ−ＮＨ_２ （ＩＩＩ）
式中、
Ｒは前記と同義である、
で表される化合物と反応させる方法。

Where
X, Y, and n are as defined above.
A compound represented by the formula
R-NH ₂ (III)
Where
R is as defined above,
The method of making it react with the compound represented by these.

  The benzylpyrimidine derivative of the formula (I) provided by the present invention exhibits a strong plant disease control action.

  The benzylpyrimidine derivative of formula (I) according to the present invention is conceptually included in the compound represented by the general formula described in Patent Document 1, but the compound of the present invention specified by the above formula (I) is patented. It is a novel compound not specifically disclosed in Document 1. The compound of the present invention represented by the above formula (I) is surprisingly substantially superior to plant diseases that are substantially superior to known structurally similar compounds specifically described in Patent Document 1. It exerts a controlling effect, and in particular, tomato plague (Phytophthora infestans), cucumber powdery mildew (Sphaerotheca fuliginea), apple spotted leaf disease (Alternaria bullye), rice blast It exhibits a particularly outstanding plant interference control action against sesame leaf blight (Cochliobolus Miyabeanus), soybean rust (Phakopsora pachyrhizi), and the like.

  Therefore, the benzylpyrimidine derivative of the formula (I) of the present invention is extremely useful as an agricultural and horticultural fungicide.

In this specification,
“Halogen” represents fluorine, chlorine, bromine or iodine, preferably fluorine or chlorine.

“C _2-6 alkyl” may be linear or branched, for example, specifically, 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, 1,3-dimethylbutyl and the like.

In the compound of the formula (I), preferably
R is 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 is indicated,
X represents fluorine, chlorine, bromine or iodine,
When Y represents fluorine or chlorine and n represents 2, two Ys may be the same or different from each other, and n represents an integer of 0 to 2.

In the compound of the formula (I), particularly preferably
R represents isopropyl, isobutyl, sec-butyl or neo-pentyl;
X represents fluorine, chlorine or bromine,
Y represents fluorine or chlorine;
n represents an integer of 0 to 2,
When n represents 1, Y is bonded to the 4-position or 5-position of the phenyl moiety, and when n is 2, two Y are bonded to the 4-position and 5-position of the phenyl moiety, and two Y may be the same or different.

  In the compound of the formula (I), when the group R has an asymmetric carbon, it includes an enantiomer (R / S configuration).

  The production method (a) can be represented by the following reaction formula when, for example, 4,6-dichloro-5- (3-chlorobenzyl) pyrimidine and isopropylamine are used as raw materials.

上記製法（ａ）において、原料である式（ＩＩ）の化合物は、その一部は従来の文献に未記載の新規化合物であり、例えば、式

In the production method (a), a part of the compound of the formula (II) as a raw material is a novel compound that has not been described in the conventional literature.

式中、
Ｘ、Ｙ及びｎは前記と同義である、
で表される化合物をハロゲン化剤、例えば、オキシ塩化リン等と、例えば、
Ｊｏｕｒｎａｌ ｏｆ Ｈｅｔｅｒｏｃｙｃｌｉｃ Ｃｈｅｍｉｓｔｒｙ，Ｖｏｌ．２９，ｐ．１３６９−１３７０，１９９２年、Ｊｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ，Ｖｏｌ．３２，Ｎｏ．２，ｐ．１５９１−１５９６，１９６７年、Ｊｏｕｒｎａｌ ｏｆ Ｍｅｄｉｃｉｎａｌ Ｃｈｅｍｉｓｔｒｙ，Ｖｏｌ．４５，Ｎｏ．１７，ｐ．３６３９−３６４８，２００２年等に記載の方法に従って反応させることにより、容易に製造することができる。

Where
X, Y, and n are as defined above.
And a halogenating agent such as phosphorus oxychloride, for example,
Journal of Heterocyclic Chemistry, Vol. 29, p. 1369-1370, 1992, Journal of Organic Chemistry, Vol. 32, no. 2, p. 1591-1596, 1967, Journal of Medicinal Chemistry, Vol. 45, no. 17, p. It can be easily produced by reacting according to the method described in 3639-3648, 2002 or the like.

  A part of the compound of the above formula (IV) is a novel compound which has not been described in the conventional literature.

式中、
Ｒ^１はＣ_１−４アルキルを示し、
Ｘ、Ｙ及びｎは前記と同義である、
で表される化合物をホルムアミジン酢酸塩又はホルムアミジン塩酸塩と、例えば、Ｊｏｕｒｎａｌ ｏｆ ｔｈｅ Ａｍｅｒｉｃａｎ Ｃｈｅｍｉｃａｌ Ｓｏｃｉｅｔｙ，Ｖｏｌ．７７，ｐ．７４５−７４９，１９５５年、Ｊｏｕｒｎａｌ ｏｆ ｔｈｅ Ａｍｅｒｉｃａｎ Ｃｈｅｍｉｃａｌ Ｓｏｃｉｅｔｙ，Ｖｏｌ．６９，ｐ．２９４１−２９４２，１９３８年、Ｊｏｕｒｎａｌ ｏｆ Ｍｅｄｉｃｉｎａｌ Ｃｈｅｍｉｓｔｒｙ，Ｖｏｌ．４５，Ｎｏ．１７，ｐ．３６３９−３６４８，２００２年等に記載される方法に従って反応させることにより容易に製造することができる。

Where
R ¹ represents C _1-4 alkyl;
X, Y, and n are as defined above.
And formamidine acetate or formamidine hydrochloride, for example, Journal of the American Chemical Society, Vol. 77, p. 745-749, 1955, Journal of the American Chemical Society, Vol. 69, p. 2941-2942, 1938, Journal of Medicinal Chemistry, Vol. 45, no. 17, p. It can be easily produced by reacting according to the method described in 3639-3648, 2002.

  A part of the above formula (V) is a novel compound not described in the conventional literature.

式中、
Ｒ^１は前記と同義である、
で表される化合物を式

Where
R ¹ is as defined above,
A compound represented by the formula

式中、
Ｘ^１はハロゲン、好ましくはクロロ、ブロモ又はヨードを示し、
Ｘ、Ｙ及びｎは前記と同義である、
で表される化合物と、例えば、日本特許公開公報特開平１１−２２８５００号、Ｊｏｕｒｎａｌ ｏｆ Ｍｅｄｉｃｉｎａｌ Ｃｈｅｍｉｓｔｒｙ，Ｖｏｌ．４５，Ｎｏ．１７，ｐ．３６３９−３６４８，２００２年等に記載される方法に従って反応させることにより容易に製造することができる。

Where
X ¹ represents halogen, preferably chloro, bromo or iodo,
X, Y, and n are as defined above.
And compounds represented by, for example, JP-A-11-228500, Journal of Medicinal Chemistry, Vol. 45, no. 17, p. It can be easily produced by reacting according to the method described in 3639-3648, 2002.

  The compounds of the above formulas (VI) and (VII) are known per se.

  In the above production method (a), the raw material compound of the formula (III) is a compound known per se.

As typical examples of the compound of the formula (II) used as a starting material in the production method (a), the following can be exemplified.
4,6-dichloro-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-dichloro-5- (3,5-dichlorobenzyl) pyrimidine,
4,6-dichloro-5- (3,4,5-trifluorobenzyl) pyrimidine and the like.

As representative examples of the compound of formula (IV) used as a raw material in the production of the compound of formula (II), the following can be exemplified.
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,
4,6-dihydroxy-5- (3,4,5-trifluorobenzyl) pyrimidine and the like.

As typical examples of the compound of the formula (V) used as a raw material in the production of the compound of the formula (IV), the following can be exemplified.
Diethyl (3-fluorobenzyl) malonate,
Diethyl (3-chlorobenzyl) malonate,
Diethyl (3-bromobenzyl) malonate,
Diethyl (3-iodobenzyl) malonate,
Diethyl (3,4-difluorobenzyl) malonate,
Diethyl (2,5-difluorobenzyl) malonate,
Diethyl (3,5-difluorobenzyl) malonate,
Diethyl (3,5-dichlorobenzyl) malonate,
Diethyl (3,4,5-trifluorobenzyl) malonate and the like.

  Representative examples of the compound of formula (VI) used as a raw material in the production of the compound of formula (V) include diethyl malonate and dimethyl malonate.

As representative examples of the compound of formula (VII) used as a raw material in the production of the compound of formula (V), the following can be exemplified.
3-fluorobenzyl bromide,
3-chlorobenzyl bromide,
3-bromobenzyl bromide,
3-iodobenzyl bromide,
3,4-difluorobenzyl bromide,
2,5-difluorobenzyl bromide,
3,5-difluorobenzyl bromide,
3,5-dichlorobenzyl bromide,
3,4,5-trifluorobenzyl bromide and the like.

Typical examples of the compound of the formula (III) used as a starting material in the production method (a) include the following.
Ethylamine,
n-propylamine,
iso-propylamine,
n-butylamine,
iso-butylamine,
sec-butylamine,
(R) -sec-butylamine,
(S) -sec-butylamine,
tert-butylamine,
n-amylamine,
iso-amylamine,
1-ethylpropylamine,
3-methyl-2-butylamine,
(R) -3-methyl-2-butylamine,
(S) -3-methyl-2-butylamine,
2,2-dimethylpropylamine,
1,3-dimethylbutylamine and the like.

Reaction of the said manufacturing method (a) can be implemented in a suitable diluent, As an example of the diluent used in that case,
Aliphatic, cycloaliphatic and aromatic hydrocarbons (which may optionally be chlorinated) such as pentane, hexane, cyclohexane, petroleum ether, ligroin, benzene, toluene, xylene,
Dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, chlorobenzene, dichlorobenzene, etc .;
Ethers such as ethyl ether, methyl ethyl ether, isopropyl ether, butyl ether,
Dioxane, dimethoxyethane (DME), tetrahydrofuran (THF), diethylene glycol dimethyl ether (DGM) and the like;
Ketones such as acetone, methyl ethyl ketone (MEK), methyl-isopropyl ketone, methyl isobutyl ketone (MIBK);
Nitriles such as acetonitrile, propionitrile,
Acrylonitrile, etc .;
Alcohols such as methanol, ethanol, isopropanol, butanol, ethylene glycol and the like;
Esters such as ethyl acetate, amyl acetate and the like;
Acid amides such as dimethylformamide (DMF), dimethylacetamide (DMA), N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone, hexamethylphosphoric triamide (HMPA) and the like;
Examples include sulfone, sulfoxides such as dimethyl sulfoxide (DMSO), sulfolane and the like; and bases such as pyridine and the like.

The production method (a) can be carried out in the presence of an acid binder, and as such an acid binder, alkali metal and alkaline earth metal hydrides, hydroxides, carbonates and bicarbonates as inorganic bases can be used. Salt etc.
Sodium hydride, lithium hydride,
Sodium bicarbonate, potassium bicarbonate, sodium carbonate, potassium carbonate,
Lithium hydroxide, sodium hydroxide, potassium hydroxide, calcium hydroxide, etc .;
Inorganic alkali metal amides such as lithium amide, sodium amide, potassium amide and the like;
Alcoholates as organic bases, tertiary amines, dialkylaminoanilines and pyridines such as triethylamine, 1,1,4,4-tetramethylethylenediamine (TMEDA), N, N-dimethylaniline, N, N-diethyl Aniline,
Pyridine, 4-dimethylaminopyridine (DMAP), 1,4-diazabicyclo [2,2,2] octane (DABCO), 1,8-diazabicyclo [5,4,0] undec-7-ene (DBU) and the like;
Organic amine hydrochlorides such as pyridine hydrochloride, triethylamine hydrochloride and the like;
Examples thereof include amine sulfonates such as pyridine p-toluenesulfonate and triethylamine p-toluenesulfonate.

  The production method (a) can be carried out within a substantially wide temperature range.

In general, it can be carried out at a temperature between about −78 and about 200 ° C., preferably between about −20 and about 180 ° C.
The reaction is preferably carried out under normal pressure, but can be operated under pressure or reduced pressure.

  In carrying out the production method (a), for example, 1.0 mol to 10.0 mol of the compound of formula (III) in a diluent such as tetrahydrofuran is added to triethylamine with respect to 1 mol of the compound of formula (II). The target compound (I) can be obtained by reacting in the presence.

  The active compounds of the formula (I) according to the invention exhibit a strong fungicidal action and can in fact be used to control unwanted phytopathogenic fungi.

  The active compounds of the formula (I) according to the invention are generally used as fungicides as fungicides (Plasmodiophoromycetes), oomycetes, zygomycetes, ascomycetes, basidiomycetes (Basidiomycetes) It can be used against various plants by Basidiomycetes and Deuteromycetes.

According to the invention, the active compounds of the formula (I) are in particular
Tomato plague (Phytophthora infestans),
Cucumber powdery mildew (Sphaerotheca furiginea),
Apple spotted leaf disease (Alternaria mary),
Gibberella fujikuroi,
Rice blast (Pyriculaia oryzae),
Excellent control effect against plant pathogens such as rice sesame leaf blight (Cochliobolus miyabeanus) and soybean rust (Phakopsora pachyrhizi).

  The active compound of the formula (I) of the present invention exhibits good compatibility with the plant at the concentration of the active compound necessary for controlling the phytopathogenic fungi. Drug treatment, treatment of rootstock or seed, and soil treatment are possible.

  Moreover, the active compound of the formula (I) of the present invention has low toxicity to warm-blooded animals and can be used safely.

  The active compound of the formula (I) of the present invention can be formulated into a usual preparation form when used as an agricultural chemical. Examples of the dosage form include liquids, wettable powders, emulsions, suspensions, powders, foams, pastes, tablets, granules, aerosols, active compound infiltration-natural and synthetic, microcapsules, seed coatings. , ULV [cold mist, warm mist] and the like.

  These preparations can be produced in a manner known per se. For example, the activator is prepared by mixing with a developing agent, i.e. a liquid diluent, solid diluent or carrier, optionally with a surfactant, i.e. emulsifier and / or dispersant and / or foam former. be able to.

  Liquid diluents or carriers generally include aromatic hydrocarbons (eg, xylene, toluene, alkylnaphthalene, etc.), chlorinated aromatic or chlorinated aliphatic hydrocarbons (eg, chlorobenzenes, ethylene chlorides, Methylene chloride, etc.), aliphatic hydrocarbons [e.g., cyclohexane, paraffins (e.g., mineral oil fractions)], alcohols (e.g., butanol, glycols, etc.) and ethers, esters, etc. thereof, ketones (e.g., Acetone, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone, etc.), strong solvents (for example, dimethylformamide, dimethyl sulfoxide, etc.), and water. When water is used as the developing agent, for example, an organic solvent can be used as an auxiliary solvent.

  Examples of the solid diluent include ground natural minerals (for example, kaolin, clay, talc, chalk, quartz, attapul guide, montmorillonite, diatomaceous earth, etc.), ground synthetic minerals (for example, highly dispersed silicic acid, alumina, silicates, etc.) Can be mentioned.

  Solid carriers for granules include, for example, crushed and fractionated rocks (eg calcite, marble, pumice, gabbro, dolomite, etc.), synthetic particles of inorganic or organic powders, organic substances (eg sawdust) , Coconuts, corn cobs, tobacco stems, etc.).

  Examples of the emulsifier and / or foaming agent include nonionic and anionic emulsifiers [for example, polyoxyethylene fatty acid ester, polyoxyethylene fatty acid alcohol ether (for example, alkylaryl polyglycol ether, alkyl sulfonate, alkyl sulfate, Aryl sulfonates, etc.)], albumin hydrolysis products, and the like.

  Examples of the dispersant include lignin sulfite waste liquid, methylcellulose and the like.

  The sticking agent can also be used in preparations (powder, granules, emulsions). Examples of the sticking agent that can be used in this case include carboxymethyl cellulose, natural and synthetic polymers (eg, gum arabic, polyvinyl alcohol, polyvinyl). Acetate).

  Colorants can also be used, such as inorganic pigments (eg, iron oxide, titanium oxide, Prussian blue, etc.), alizarin dyes, organic dyes such as azo dyes or metal phthalocyanine dyes, iron, Mention may be made of trace elements such as manganese, boron, copper, cobalt, molybdenum, zinc or salts of these metals.

  The formulations in general contain the active compounds of the formula (I) according to the invention in a proportion in the range from 0.1 to 95% by weight, preferably from 0.5 to 90% by weight.

  The active compounds of the formula (I) according to the invention can be used in the above formulations or in various use forms, for example in other known active compounds such as fungicides (fungisides, bacteriides), insecticides, acaricides, nematocides. , Herbicides, avian repellents, growth regulators, fertilizers and / or soil conditioners.

  When the active compound of the formula (I) of the present invention is actually used, it is used directly as it is, or in the form of a preparation for spraying, an emulsion, a suspension, a powder, a tablet, a paste, a microcapsule, a granule, etc. It can be used or can be used in a use form prepared by further dilution. The active compound is then applied in a conventional manner, for example, liquid watering, dipping, spraying, spraying, suspension formation, application, dusting, dusting, powder dressing, wet dressing, wet coating, pasty. It can be applied by a method such as coating or robe coating.

  In the treatment of each part of the plant body, the concentration of the active compound in the actual use form can vary within a substantial range, but is generally 0.0001 to 1% by weight, preferably 0.001. It can be in the range of -0.5 wt%.

  In seed treatment, the active compound can be used in a proportion of generally 0.001 to 50 g, preferably 0.01 to 10 g, per 1 kg of seed.

  In soil treatment, the active compound can be used at a concentration generally in the range of 0.00001 to 0.1% by weight, in particular 0.0001 to 0.02% by weight, based on the point of action.

  Next, although the specific example shows the manufacture and use of the compound of this invention by the following example, this invention should not be limited only to these.

<Examples of compound production>
Synthesis example 1

４，６−ジクロロ−５−（３，５−ジフルオロベンジル）ピリミジン（１６０ｍｇ、０．５８ｍｍｏｌ）をテトラヒドロフラン（２０ｍｌ）に溶解し、次いでイソプロピルアミン（２１０μｌ、２．４ｍｍｏｌ）およびトリエチルアミン（１７０μｌ、１．２ｍｍｏｌ）を加え、７時間加熱還流した後、さらにイソプロピルアミン（４２０μｌ、４．８ｍｍｏｌ）を加え５時間加熱還流した。反応終了後、沈殿物を除去後、濾液を減圧下濃縮し、残渣をシリカゲルカラムクロマトグラフィー（溶出溶媒： ｎ−ヘキサン：酢酸エチル＝９：１）にて精製し、５−（３，５−ジフルオロベンジル）−４−クロロ−６−イソプロピルアミノピリミジン（１５０ｍｇ、収率８８％）を得た。
ｍｐ １１９−１２１℃

4,6-Dichloro-5- (3,5-difluorobenzyl) pyrimidine (160 mg, 0.58 mmol) was dissolved in tetrahydrofuran (20 ml), then isopropylamine (210 μl, 2.4 mmol) and triethylamine (170 μl, 1. 2 mmol) was added and heated to reflux for 7 hours, and then isopropylamine (420 μl, 4.8 mmol) was further added and heated to reflux for 5 hours. After completion of the reaction, the precipitate was removed, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (elution solvent: n-hexane: ethyl acetate = 9: 1) to give 5- (3,5- Difluorobenzyl) -4-chloro-6-isopropylaminopyrimidine (150 mg, 88% yield) was obtained.
mp 119-121 ° C

Synthesis example 2

４，６−ジクロロ−５−（３，５−ジフルオロベンジル）ピリミジン（１７０ｍｇ、０．６ｍｍｏｌ）をテトラヒドロフラン（２０ｍｌ）に溶解し、次いでイソブチルアミン（２４０μｌ、２．４ｍｍｏｌ）およびトリエチルアミン（２５０μｌ、１．８ｍｍｏｌ）を加え、７時間加熱還流した。反応終了後、沈殿物を除去後、濾液を減圧下濃縮し、残渣をシリカゲルカラムクロマトグラフィー（溶出溶媒： ｎ−ヘキサン：酢酸エチル＝９：１）にて精製し、５−（３，５−ジフルオロベンジル）−４−クロロ−６−イソブチルアミノピリミジン（１８０ｍｇ、収率９７％）を得た。
ｍｐ ８２−８３℃

4,6-Dichloro-5- (3,5-difluorobenzyl) pyrimidine (170 mg, 0.6 mmol) was dissolved in tetrahydrofuran (20 ml), then isobutylamine (240 μl, 2.4 mmol) and triethylamine (250 μl, 1. 8 mmol) was added and heated to reflux for 7 hours. After completion of the reaction, the precipitate was removed, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (elution solvent: n-hexane: ethyl acetate = 9: 1) to give 5- (3,5- Difluorobenzyl) -4-chloro-6-isobutylaminopyrimidine (180 mg, 97% yield) was obtained.
mp 82-83 ° C

Synthesis example 3

４，６−ジクロロ−５−（３−クロロベンジル）ピリミジン（２７３ｍｇ、１．０ｍｍｏｌ）をテトラヒドロフラン（４ｍｌ）、エタノール（５００μｌ）に溶解し、次いでイソプロピルアミン（２６０μｌ、３．０ｍｍｏｌ）およびトリエチルアミン（４２０μｌ、３．０ｍｍｏｌ）を加え、マイクロウェーブリアクター（Ｉｎｉｔｉａｔｏｒ^ＴＭ， Ｂｉｏｔａｇｅ社）によって、１８０℃にて２５分間反応させた。反応終了後、沈殿物を除去後、濾液を減圧下濃縮し、残渣をシリカゲルカラムクロマトグラフィー（溶出溶媒： ｎ−ヘキサン：酢酸エチル＝９：１）にて精製し、５−（３−クロロベンジル）−４−クロロ−６−イソプロピルアミノピリミジン（２６１ｍｇ、収率８８％）を得た。
ｍｐ １１０−１１２℃

4,6-Dichloro-5- (3-chlorobenzyl) pyrimidine (273 mg, 1.0 mmol) was dissolved in tetrahydrofuran (4 ml), ethanol (500 μl), then isopropylamine (260 μl, 3.0 mmol) and triethylamine (420 μl). , 3.0 mmol) was added, and the mixture was reacted at 180 ° C. for 25 minutes using a microwave reactor (Initiator ^™ , Biotage). After completion of the reaction, the precipitate was removed, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (elution solvent: n-hexane: ethyl acetate = 9: 1) to give 5- (3-chlorobenzyl). ) -4-chloro-6-isopropylaminopyrimidine (261 mg, yield 88%) was obtained.
mp 110-112 ° C

  The compounds obtained in the same manner as in Synthesis Examples 1 to 3 are shown in Table 1 together with the compounds synthesized in Synthesis Examples 1 to 3.

Reference Example 1 (Production of Intermediate)

３−フルオロベンジルブロミド（５０ｇ、０．２６ｍｏｌ）、ジエチルマロネート（３２０ｍｌ、２．１ｍｏｌ）および炭酸カリウム（８０ｇ、０．５８ｍｏｌ）をアセトン（３００ｍｌ）に縣濁し７５℃で６時間攪拌した。反応終了後、沈殿物を濾過、アセトン洗浄した。減圧下、溶媒、過剰のマロン酸ジエチルを除去し、残渣をシリカゲルカラムクロマトグラフィー（溶出溶媒： ｎ−ヘキサン：酢酸エチル＝２０：１）にて精製し、ジエチル（３−フルオロベンジル）マロネート（６２ｇ）を得た。

3-Fluorobenzyl bromide (50 g, 0.26 mol), diethyl malonate (320 ml, 2.1 mol) and potassium carbonate (80 g, 0.58 mol) were suspended in acetone (300 ml) and stirred at 75 ° C. for 6 hours. After completion of the reaction, the precipitate was filtered and washed with acetone. Under reduced pressure, the solvent and excess diethyl malonate were removed, and the residue was purified by silica gel column chromatography (elution solvent: n-hexane: ethyl acetate = 20: 1) to give diethyl (3-fluorobenzyl) malonate (62 g). )

Reference Example 2 (Production of Intermediate)

ホルムアミジン酢酸塩（１１．５ｇ、０．１１ｍｏｌ）、エタノール（２００ｍｌ）の縣濁液に氷冷下、ナトリウムメトキシド２８％メタノール溶液（５８ｇ、０．３ｍｏｌ）を加え、氷冷下のまま２０分間攪拌した後、ジエチル（３−フルオロベンジル）マロネート（２６．８ｇ、０．１ｍｏｌ）を加えた。氷冷下のまま３０分間攪拌し、室温で１５時間攪拌した後、１５時間加熱還流した。減圧下、エタノールを除去し、水を加えた。氷冷下、濃塩酸（３０ｇ）を加えて生成した沈殿を瀘別し、水、次いでｎ−ヘキサンで洗浄後、デシケーターで乾燥し、４，６−ジヒドロキシ−５−（３−フルオロベンジル）ピリミジン（２１ｇ）を得た。
そのまま精製することなく、次の反応に用いた。

Sodium methoxide 28% methanol solution (58 g, 0.3 mol) was added to a suspension of formamidine acetate (11.5 g, 0.11 mol) and ethanol (200 ml) under ice cooling, and the mixture was kept under ice cooling. After stirring for minutes, diethyl (3-fluorobenzyl) malonate (26.8 g, 0.1 mol) was added. The mixture was stirred for 30 minutes with cooling on ice, stirred at room temperature for 15 hours, and then heated to reflux for 15 hours. Ethanol was removed under reduced pressure and water was added. Concentrated hydrochloric acid (30 g) was added under ice-cooling, and the resulting precipitate was filtered off, washed with water and then with n-hexane, dried with a desiccator, and 4,6-dihydroxy-5- (3-fluorobenzyl) pyrimidine (21 g) was obtained.
The product was used in the next reaction without purification.

Reference Example 3 (Production of Intermediate)

４，６−ジヒドロキシ−５−（３−フルオロベンジル）ピリミジン（２１ｇ）にＮ，Ｎ−ジメチルアニリン（２５ｍｌ）、オキシ塩化リン（１５０ｍｌ）を加え１０時間加熱還流した。反応終了後、減圧下、過剰のオキシ塩化リンを除去し、氷水を加え、酢酸エチルで抽出した。酢酸エチル層を無水硫酸マグネシウムで乾燥し、シリカゲルを詰めたグラスフィルターにて酢酸エチルを用いて濾過した。瀘液を減圧下濃縮し得られた粗製生成物をエタノールに溶解し、氷水を加え、生成した沈殿を瀘別し、水で洗浄後、デシケーターで乾燥し、４，６−ジクロロ−５−（３−フルオロベンジル）ピリミジン（２２．７ｇ）を得た。
ｍｐ ４７−４９℃

N, N-dimethylaniline (25 ml) and phosphorus oxychloride (150 ml) were added to 4,6-dihydroxy-5- (3-fluorobenzyl) pyrimidine (21 g), and the mixture was heated to reflux for 10 hours. After completion of the reaction, excess phosphorus oxychloride was removed under reduced pressure, ice water was added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and filtered through a glass filter packed with silica gel using ethyl acetate. The crude product obtained by concentrating the filtrate under reduced pressure was dissolved in ethanol, ice water was added, the formed precipitate was filtered off, washed with water, dried in a desiccator, and 4,6-dichloro-5- ( 3-Fluorobenzyl) pyrimidine (22.7 g) was obtained.
mp 47-49 ° C

In the same manner as in Reference Examples 1 to 3, for example, the following compounds are obtained as typical examples.
4,6-dichloro-5- (2,5-difluorobenzyl) pyrimidine; mp 115-117 ° C,
4,6-dichloro-5- (3,4-difluorobenzyl) pyrimidine; mp 61-69 ° C.,
4,6-dichloro-5- (3,4,5-trifluorobenzyl) pyrimidine; n _D ²⁰ 1.4750,
4,6-dichloro-5- (3,5-dichlorobenzyl) pyrimidine; mp 109-110 ° C.

<Biological test example>
Comparative compound

（Ｃ−１〜Ｃ−５は特許文献１に開示される類似化合物である）。

(C-1 to C-5 are similar compounds disclosed in Patent Document 1).

Test Example 1 : Preparation of test compounds for foliar spray efficacy test against tomato plague Active compound: 5 parts by weight Organic solvent: Acetone 142.5 parts by weight Emulsifier: 7.5 parts by weight of polyoxyethylene alkylphenyl ether Above active compound, acetone And an emulsifier are mixed, diluted with water to a predetermined concentration, and used for the test.

Test method Tomato (variety: Resina) was cultivated in a plastic pot having a diameter of 4 cm, and 6 ml of a predetermined concentration diluted solution of an active compound prepared in advance was sprayed on small seedlings reaching 2-3 leaves. One day after spraying, the zoosporangia formed on the tomato plague ( Phytophthora infestans ) lesion, which had been caused by infecting the tomato in advance, was washed off in distilled water with a brush to obtain a suspension. Using this suspension as an inoculum, the treated plants were spray-inoculated (once) and kept at 20 ° C. and 100% relative humidity for infection. Four days after the inoculation, the morbidity per pot was classified and the control value (%) was obtained. The phytotoxicity was also investigated at the same time. This test is the average of the results of 3 pots in 1 district.

The morbidity evaluation and control value calculation methods are as follows.
Disease severity Rate of lesion area (%)
0 0
0.5 Less than 2 1 Less than 2 to 5 2 Less than 5 to 10 3 Less than 10 to 20 4 Less than 20 to 40 5 40 or more

Control value (%) = (1- {morbidity of treated area ÷ morbidity of untreated area}) × 100

  As representative examples, compound Nos. 1-5, 1-10, 1-14, 1-17, 1-22, 1-25, 1-27, 1-31, 1-42, 1-44, 1-47 Table 2 below shows the results of investigation on the compounds and the compounds of Comparative Compound Nos. C-1, C-2, C-3, C-4, and C-5. In the compound of the present invention, no phytotoxicity was observed.

Test Example 2 : Test method of foliage spraying efficacy test method for cucumber powdery mildew Cucumber (variety: Sagamihanjiro) was cultivated in a plastic pot with a diameter of 4 cm, and was prepared in the same manner as in Test Example 1 above to a small seedling that reached the cotyledon. 6 ml of a predetermined concentration dilution of the active compound was sprayed per 3 pots. One day after spraying, spore powdery mildew ( Sphaerotheca furiginae ) spores previously infected with cucumber were washed off in distilled water to give a suspension. This suspension was spray-inoculated (once) to the treated plants as an inoculum and infected in the greenhouse. Seven days after the inoculation, the morbidity per pot was classified and the control value (%) was obtained. The phytotoxicity was also investigated at the same time. This test is the average of the results of 3 pots in 1 district.

The morbidity evaluation and control value calculation methods are as follows.
Disease severity Rate of lesion area (%)
0 0
0.5 Less than 2 1 Less than 2 to 5 2 Less than 5 to 10 3 Less than 10 to 20 4 Less than 20 to 40 5 40 or more

Control value (%) = (1- {morbidity of treated area ÷ morbidity of untreated area}) × 100

  As representative examples, compounds of compound numbers 1-5, 1-6, 1-7, 1-9, 1-12, 1-42 and comparative compound numbers C-1, C-2, C-3, C-4 Table 3 below shows the results of investigation on the compounds of C-5 and C-5. In the compound of the present invention, no phytotoxicity was observed.

Test Example 3 : Test method of foliage spraying efficacy test for rice blast disease Rice (cultivar: Koshihikari) was cultivated in a plastic pot with a diameter of 4 cm and prepared in the same manner as in Test Example 1 from 1.5 to 2 leaves. 6 ml of a predetermined concentration dilution of the active compound was sprayed per 3 pots. One day after the spraying, an artificially cultured spore suspension of rice blast fungus ( Pyricularia oryzae ) was spray-inoculated (once) and kept at 25 ° C. and 100% relative humidity for infection. Seven days after the inoculation, the morbidity per pot was classified and the control value (%) was determined. The phytotoxicity was also investigated at the same time. This test is the average of the results of 3 pots in 1 district.

The morbidity evaluation and control value calculation methods are as follows.
Disease severity Rate of lesion area (%)
0 0
0.5 Less than 2 1 Less than 2 to 5 2 Less than 5 to 10 3 Less than 10 to 20 4 Less than 20 to 40 5 40 or more

Control value (%) = (1- {morbidity of treated area ÷ morbidity of untreated area}) × 100

  As representative examples, compound numbers 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, 1-56 and comparative compound numbers C-1, C-2, C- Table 4 below shows the results of investigation on the compounds of 3, C-4, and C-5. In the compound of the present invention, no phytotoxicity was observed.

Test Example 4 : Stem and leaf spraying efficacy test for soybean rust disease Test method Soybean (variety: Miyagi shirome) was cultivated in a plastic pot with a diameter of 7.5 cm, and a plant that reached 1.5 leaf stage was tested in the same manner as in Test Example 1 above. 6 ml of a predetermined concentration diluted solution of the active compound thus prepared was sprayed per 3 pots. One day after the spraying, the soybean rust spores ( Phakopsora pachyrhizi ) spores previously infected with the soybean were washed off in distilled water to obtain a suspension. This suspension was spray-inoculated (once) to the treated plants as an inoculum and infected in the greenhouse. Eleven days after the inoculation, the morbidity per pot was classified and the control value (%) was obtained. The phytotoxicity was also investigated at the same time. This test is the average of the results of 3 pots in 1 district.

The morbidity evaluation and control value calculation methods are as follows.
Disease severity Rate of lesion area (%)
0 0
0.5 Less than 2 1 Less than 2 to 5 2 Less than 5 to 10 3 Less than 10 to 20 4 Less than 20 to 40 5 40 or more

Control value (%) = (1- {morbidity of treated area ÷ morbidity of untreated area}) × 100

Test results As representative examples, compound numbers 1-5, 1-6, 1-7, 1-9, 1-11, 1-12, 1-21, 1-27, 1-35, 1-36, 1- The compounds of 39, 1-42, 1-43, 1-46, 1-49, 1-51, 1-57 and 1-58 showed a control value of 80% or more at the drug concentration (500 ppm). In the compound of the present invention, no phytotoxicity was observed.

<Formulation example>
Formulation Example 1 (Granule)
Add water (25 parts) to a mixture of the present compound number 1-12 (10 parts), bentonite (montmorillonite) (30 parts), talc (talc) (58 parts) and lignin sulfonate (2 parts) It hatches and is made into 10-40 mesh granule with an extrusion-type granulator, and it dries at 40-50 degreeC to make a granule.

Formulation Example 2 (Granule)
Clay mineral particles (95 parts) having a particle size distribution of 0.2 to 2 mm were placed in a rotary mixer, and under rotation, the present compound No. 1-47 (5 parts) was sprayed together with a liquid diluent and moistened evenly. Then, it dries at 40-50 degreeC and is set as a granule.

Formulation Example 3 (Emulsion)
Compound No. 1-18 (30 parts) of the present invention, xylene (55 parts), polyoxyethylene alkylphenyl ether (8 parts) and calcium alkylbenzenesulfonate (7 parts) are mixed and stirred to obtain an emulsion.

Formulation Example 4 (Wetting agent)
Compound No. 1-5 (15 parts) of the present invention, a mixture of white carbon (hydrous amorphous silicon oxide fine powder) and powdered clay (1: 5) (80 parts), sodium alkylbenzenesulfonate (2 parts) and alkylnaphthalene Sodium sulfonate formalin polymer (3 parts) is mixed with powder to obtain a wettable powder.

Formulation Example 5 (Hydrated Granules)
Compound No. 1-42 (20 parts) of the present invention, sodium lignin sulfonate (30 parts), bentonite (15 parts) and calcined diatomaceous earth powder (35 parts) were thoroughly mixed, water was added, and a 0.3 mm screen Extrude and dry to make hydrated granules.

  The novel benzylpyrimidine derivative of the present invention has excellent properties as an agricultural and horticultural fungicide, as is apparent from the above biological test examples.

Claims (4)

formula

Where
R represents C _2-6 alkyl;
X represents halogen,
Y represents halogen, and when n represents 2, two Ys may be the same or different from each other, and n represents an integer of 0 to 2,
A benzylpyrimidine derivative represented by: R is 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 is indicated,
X represents fluorine, chlorine, bromine or iodine,
When Y represents fluorine or chlorine and n represents 2, two Ys may be the same or different from each other, and n represents an integer of 0 to 2,
The compound of claim 1. R represents isopropyl, isobutyl, sec-butyl or neo-pentyl;
X represents fluorine, chlorine or bromine,
Y represents fluorine or chlorine;
n represents an integer of 0 to 2,
When n represents 1, Y is bonded to the 4-position or 5-position of the phenyl moiety, and when n is 2, two Y are bonded to the 4-position and 5-position of the phenyl moiety, and two Y may be the same or different,
The compound of claim 1.   An agricultural and horticultural fungicide containing the compound according to claim 1, 2 or 3 as an active ingredient.