RU2255088C2 - Benzoylpyridine derivative or its salt, fungicide comprising its as active component, methods for its preparing and intermediate compounds for its preparing - Google Patents

Abstract

FIELD: organic chemistry, chemical technology, fungicides.

SUBSTANCE: invention describes derivative of benzoylpyridine of the formula (I) or its salt:

wherein X represents halogen atom, (C₁-C₆)-alkoxy-group optionally substituted with a substitute taken among halogen atom, phenyl, methoxy-, methylthio-, dimethylamino-group, vinyl or ethynyl; phenoxy-group, (C₃-C₆)-cycloalkoxy-group, hydroxyl group, (C₁-C₆)-alkyl group, (C₂-C₆)-alkenyl group, CF₃, (C₁-C₆)-alkylthio-group, (C₁-C₆)-alkoxycarbonyl group, (C₁-C₆)-dialkylaminocarbonyl group, (C₁-C₆)-alkylcarbonyloxy-group, (C₁-C₆)-alkylcarbonyl group, amino-group, (C₁-C₄)-alkylamino-group or di-(C₁-C₄)-alkylamino-group; n represents 1, 2, 3 or 4; R¹ represents (C₁-C₆)-alkyl group; R² represents (C₁-C₆)-alkyl group, (C₁-C₆)-alkoxy-group optionally substituted with phenyl, phenoxy-group, (C₃-C₁₀)-cycloalkyloxy-group or hydroxyl group; m = 1, 2 or 3 under condition that if m = 2 then R² can form ring -OCH₂O- (with exception when pyridine ring is substituted with benzoyl group at 2-position; pyridine ring is substituted with (C₁-C₆)-alkoxy-group, hydroxyl group or benzyloxy-group; n = 1; m = 1 or 2). Also, invention describes fungicide comprising compound of the formula (I) or it salt as an active component, methods for preparing derivatives of benzoylpyridine, phenylpyridylmethanol that is an intermediate compounds used for synthesis of compound of the formula (I). Invention provides fungicide properties of compound of the formula (I) or its salt.

EFFECT: improved method for preparing, valuable properties of compounds.

17 cl, 36 tbl, 4 ex

Description

Field of Invention

The present invention relates to a new derivative of benzoylpyridine or its salt, to a fungicide containing it as an active ingredient, to a method for its preparation and to intermediate compounds for its preparation.

BACKGROUND OF THE INVENTION

Derivatives of benzoylpyridine, which are analogues of the compounds of the present invention, can be compounds disclosed, for example, in WO99 / 41237, WO99 / 38845, WO96 / 17829, JP-A-7-309837 and JP-A-2-275858. However, they differ from the compounds of the present invention. Furthermore, the uses for these compounds are different from the uses for the compounds of the present invention.

Many of the commonly used fungicides have specific characteristics in terms of controlling the pests that cause plant diseases. Some of them (fungicides) are characterized by a slightly weaker healing effect compared to the prophylactic effect, and some have a residual effect that lasts only a relatively short period of time, so in some cases their ability to control pests is insufficient in practice. Accordingly, it was highly desirable to create new compounds that would be very effective in controlling pests that cause plant diseases.

Description of the invention

The authors of the present invention have undertaken intensive research to overcome the above problems and as a result found that the use of the compound represented by formula (I) as an active ingredient provides an excellent prophylactic effect and healing effect against various plant diseases, especially against powdery mildew of barley, vegetables , fruits and flowering plants, and thus, the present invention has been completed.

Thus, the present invention relates to a benzoylpyridine derivative represented by the formula (I), or a salt thereof

where X represents a halogen atom, a nitro group, a substituted alkoxy group, a substituted aryloxy group, a substituted cycloalkoxy group, a hydroxyl group, a substituted hydrocarbon group, a substituted alkylthio group, a cyano group, a carboxyl group that can be esterified or amidated, or a substituted amino; n is 1, 2, 3 or 4; R ¹ represents a substituted alkyl group; R ² represents a substituted alkyl group, a substituted alkoxy group, a substituted aryloxy group, a substituted cycloalkoxy group or a hydroxyl group; and m is 1, 2, 3, or 4, provided that if m is at least 2, R ² may contain an oxygen atom to form a fused ring (unless the pyridine ring is substituted with a benzoyl group in the 2-position ; the pyridine ring is substituted with an alkoxy group, a hydroxyl group or a benzyloxy group at the 3-position; and n is 1, m is 1 or 2), a fungicide containing it as an active ingredient, a method for its preparation and an intermediate for its preparation.

The halogen atom designated X may be, for example, fluorine, chlorine, bromine or iodine, and preferably, for example, fluorine, chlorine or bromine can be used. The alkoxy moiety in the substituted alkoxy group represented by each of X and R ² may be, for example, C _1-6 alkoxy (such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy or tert-butoxy), and preferably be, for example, C _1-4 alkoxy (such as methoxy or ethoxy). In addition, secondary substituents of the substituted alkoxy group may be from 1 to 5 substituents, which may be the same or different and which are selected from the group consisting of aryl, aryloxy, hydroxyl, nitro, nitroxy, halogen (such as fluorine, chlorine, bromine or iodine ), haloalkoxy (such as C _1-4 haloalkoxy, such as CF ₃ O or HCF ₂ O), cycloalkyl, amino, alkylthio and cyano. Of these substituted alkoxy groups, an unsubstituted alkoxy group is preferred, a C _1-4 alkoxy group is particularly preferred.

As the aryl moiety in the substituted aryloxy group designated as X, there may be mentioned polycyclic groups of the fused type, such as naphthyl and phenyl, with phenyl being preferred. The secondary substituent on the substituted aryloxy group may be, for example, halogen, alkyl, alkoxy or hydroxyl. Of the substituted aryloxy groups, a phenoxy group is most preferred.

The cycloalkyl moiety in the displaceable cycloalkoxy group denoted by X is usually a moiety containing from 3 to 10 carbon atoms and a monocyclic group such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cyclooctyl, and condensed polycyclic groups may also be mentioned. However, a monocyclic group is preferred. The secondary substituent of the substituted cycloalkoxy group may be, for example, halogen, alkyl, alkoxy or hydroxyl. Of these substituted cycloalkoxy groups, cyclohexyloxy is most preferred.

The hydrocarbon moiety in the substituted hydrocarbon group represented by X may be, for example, a C _1-6 alkyl group (such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl or tert-butyl), C _2-6 alkenyl (such as vinyl , allyl, isopropenyl or 3-methyl-2-butenyl), C _2-6 alkynyl (such as ethynyl, 1-propynyl or 2-propynyl), C _3-6 cycloalkyl (such as cyclopropyl, cyclopentyl or cyclohexyl), or C _6-10 aryl. In addition, the secondary substituents of the substituted hydrocarbon group may be from one to five substituents, which may be the same or different, and which are selected from the group consisting of aryl, aryloxy, hydroxyl, nitro, nitroxy, halogen (such as fluorine, chlorine, bromine or iodine), haloalkoxy (such as C _1-4 haloalkoxy, such as CF ₃ O or HCF ₂ O), cycloalkyl, amino, alkylthio and cyano. Of these substituted hydrocarbon groups, substituted alkyl groups are preferred, and alkyl groups are particularly preferred. In addition, among the alkyl groups, C _1-4 alkyl groups are most preferred.

The alkylthio moiety in the substituted alkylthio group denoted by X can be, for example, C _1-6 alkylthio (such as methylthio, ethylthio, propylthio, isopropylthio, butylthio, isobutylthio or tert-butylthio) and preferably C _1-4 alkylthio (such as methylthio or ethylthio). Of these alkylthio groups which may have substituents, an alkylthio group is preferred, a C _1-4 alkylthio group is particularly preferred. Secondary substituents on the substituted alkylthio group may be from one to five substituents, which may be the same or different and which are selected from the group consisting of aryl, aryloxy, hydroxyl, nitro, nitroxy, halogen (such as fluorine, chlorine, bromine or iodine), haloalkoxy (such as C _1-4 haloalkoxy, such as CF ₃ O or HCF ₂ O) and cyano.

A carboxyl group that can be esterified or amidated, designated X, can be, for example, a carboxyl group that can be esterified, such as a C _1-6 alkoxycarbonyl group (such as, for example, a methoxycarbonyl group, an ethoxycarbonyl group, a propoxycarbonyl group, an isopropoxycarbonyl group, butoxycarbonyl group, isobutoxycarbonyl group or tert-butoxycarbonyl group), nitroxy-C _1-4 alkoxyaminocarbonyl group (such as 2-nitroxyethoxycarbonyl group a or a 3-nitroxypropoxycarbonyl group), a phenyl-C _1-4 alkoxycarbonyl group (such as a benzyloxycarbonyl group or a phenylethoxycarbonyl group); or a carboxyl group that may be amidated, such as a carbamoyl group, a C _1-6 monoalkylaminocarbonyl group (such as a methylaminocarbonyl group, an ethylaminocarbonyl group, a propylaminocarbonyl group, an isopropylaminocarbonyl group, a butylaminocarbonyl group, an isobutylaminocarbonyl group, or t- _{1) 6} dialkylaminocarbonyl group (such as dimethylaminocarbonyl group, diethylaminocarbonyl group, dipropylaminocarbonyl group, diisopropyl a minocarbonyl group, a dibutylaminocarbonyl group or an isobutylaminocarbonyl group), a nitroxy-C _1-4 alkylaminocarbonyl group (such as a 2-nitroxyethylaminocarbonyl group or a 3-nitroxypropylaminocarbonyl group), a phenyl-C _1-4 alkylaminocarbonyl-phenyl group (such as ), C _3-6 -tsikloalkilaminokarbonilnaya group (such as a cyclopropylaminocarbonyl group) or a group tsiklopentilaminokarbonilnaya tsiklogeksilaminokarbonilnaya group, cyclic kai aminocarbonyl group (such as a morpholinocarbonyl group, piperidinokarbonilnaya group pirrolidinokarbonilnaya tiomorfolinokarbonilnaya group or group) or an aminocarbonyl group.

The substituted amino group denoted by X may, for example, be an amino group or an alkylamino group such as a monoalkylamino group or a dialkylamino group. The alkyl moiety in the alkylamino group (monoalkylamino group or dialkylamino group) is preferably C _1-4 alkyl. Secondary substituents on the substituted amino group may be from one to five substituents, which may be the same or different and which are selected from the group consisting of aryl, aryloxy, hydroxyl, nitro, nitroxy, halogen (such as fluorine, chlorine, bromine or iodine), haloalkoxy (such as C _1-4 haloalkoxy, such as CF ₃ O or HCF ₂ O), cycloalkyl, amino, alkylthio and cyano.

The alkyl moiety in the substituted alkyl group designated by each of R ¹ and R ² is preferably C _1-6 alkyl (such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl or tert-butyl), and C _{1- is} preferred among them. ₄ alkyl. Secondary substituents of the substituted alkyl group may be from one to five substituents, which may be the same or different and which are selected from the group consisting of aryl, aryloxy, hydroxyl, nitro, nitroxy, halogen (such as fluorine, chlorine, bromine or iodine), haloalkoxy (such as C _1-4 haloalkoxy, such as CF ₃ O or HCF ₂ O), cycloalkyl, amino, alkylthio and cyano. Of these substituted alkyl groups, an unsubstituted alkyl group is preferred, and a C _1-4 alkyl group is particularly preferred. Among them, a methyl group is most preferred.

The alkoxy moiety in the displaceable alkoxy group designated as R ² is preferably C _1-6 alkoxy (such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy or tert-butoxy), and among them, C _1-4 alkoxy is preferred. Secondary substituents of the substituted alkyl group may be from one to five substituents, which may be the same or different and which are selected from the group consisting of an aryl group, an aryloxy group, a hydroxyl group, a nitro group, a nitroxy group, halogen atoms (such as fluorine, chlorine, bromine or iodine), haloalkoxy groups (such as a C _1-4 haloalkoxy group, such as CF ₃ O or HCF ₂ O), a cycloalkyl group, an amino group, an alkylthio group and a cyano group. Of these substituted alkoxy groups, an unsubstituted alkoxy group is preferred.

As the aryl moiety in the substituted aryloxy group designated R ² , condensed-type polycyclic groups such as naphthyl and also phenyl can be mentioned, with phenyl being preferred. Secondary substituents of the substituted aryloxy group may be, for example, a halogen atom, an alkyl group, an alkoxy group or a hydroxyl group. Of these substituted aryloxy groups, unsubstituted phenoxy is most preferred.

The cycloalkyl moiety in the displaceable cycloalkoxy group designated R ² is typically a moiety that contains from 3 to 10 carbon atoms and a monocyclic group such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cyclooctyl, as well as a fused-type polycyclic group. However, a monocyclic group is preferred. The secondary substituent on the substituted cycloalkoxy group may, for example, be a halogen atom, alkyl, alkoxy or hydroxyl. Of these substituted cycloalkoxy groups, unsubstituted cyclohexyloxy group is most preferred.

Finally, the aryl moiety, cycloalkyl group and alkylthio group in the secondary substituent of the substituent designated X, R ¹ and R ² have the meanings indicated for the substituents designated X, R ¹ , R ² and R ³ .

The compound represented by formula (I) can form a salt with an acidic compound, and it can form, for example, an inorganic salt such as hydrochloride, hydrobromide, phosphate, sulfate or nitrate, or an organic salt such as acetate, benzoate, para-toluenesulfonate , methanesulfonate or propanesulfonate.

Preferred Embodiment

Some preferred embodiments of benzoylpyridine derivatives represented by formula (I) are shown below. These compounds can be combined with each other. In addition, these compounds are useful as fungicides.

R ^{2 '} , R ^2'' and R ^2''' have the meanings indicated for R ² and X ¹ , X ² , X ³ and X ⁴ have the meanings indicated above for X.

(1) A benzoylpyridine derivative represented by the formula (I ′) or a salt thereof

where X, n and R ¹ have the meanings given above for general formula (I), R ^{2 ′} represents a substituted alkyl group, a substituted alkoxy group, a substituted aryloxy group, a substituted cycloalkoxy group or a hydroxyl group, p is 1, 2 or 3, and R ^{2 ′ ''} represents a substituted alkoxy group or hydroxyl group, provided that at least two of R ^{2 '} and R ^2'' can contain an oxygen atom to form a fused ring (except when the pyridine ring is substituted by a benzoyl group at the 2-position; pyridine the ring is substituted by alkoxy group, hydroxyl group or benzyloxy group at the 3-position; and n is 1, p is 1).

(2) A benzoylpyridine derivative or a salt thereof according to the above (1), which is represented by the formula (I ″)

where X represents a halogen atom, a nitro group, a substituted alkoxy group, a substituted aryloxy group, a substituted cycloalkoxy group, a substituted hydrocarbon group, a substituted alkylthio group, a cyano group, a carboxyl group which may be esterified or amidated, or a substituted amino group; n is 1, 2,3 or 4; R ¹ represents an alkyl group; R ^{2 '} represents a substituted alkyl group, a substituted alkoxy group, a substituted aryloxy group or a substituted cycloalkoxy group; p is 1, 2 or 3; and each of R ^{2 ″} and R ^{2 ″ ″} represents a substituted alkoxy group.

(3) The benzoylpyridine derivative or a salt thereof according to the above (2), wherein X represents a halogen atom, a nitro group, a substituted alkoxy group, a substituted cycloalkoxy group, an alkyl group, a substituted alkylthio group or an amino group.

(4) A benzoylpyridine derivative or a salt thereof according to the above (3), represented by the formula (I ″):

where X represents a halogen atom, a nitro group, a substituted alkoxy group, a substituted cycloalkoxy group, an alkyl group, a substituted alkylthio group or a substituted amino group; n is 1, 2, 3, or 4; R ¹ represents an alkyl group; R ² represents a substituted alkyl group, a substituted alkoxy group, a substituted aryloxy group or a substituted cycloalkoxy group; p is 1, 2 or 3; each of R ^{2 ″} and R ^{2 ″ ″} represents a substituted alkoxy group (except in the case where the pyridine ring is substituted with a benzoyl group at the 3-position and the pyridine ring contains a CF ₃ group in at least one of the 2,6-positions )

(5) A benzoylpyridine derivative or a salt thereof according to the above (1), represented by the formula (I ″)

where X represents a halogen atom, a substituted alkoxy group, an alkyl group, a CF ₃ group or an alkylthio group; n is 1, 2, 3 or 4; R ¹ represents an alkyl group; R ² represents a substituted alkyl group, a substituted alkoxy group or a substituted cycloalkoxy group; p is 1, 2 or 3; and each of R ^{2 ″} and R ^{2 ″ ″} represents a substituted alkoxy group.

(6) A benzoylpyridine derivative or a salt thereof according to the above (5), represented by the formula (I ″)

where X represents a halogen atom, a substituted alkoxy group, an alkyl group, a CF ₃ group or an alkylthio group; n is 1, 2, 3, or 4; R ¹ represents an alkyl group; R ^{2 '} represents a substituted alkyl group, a substituted aryloxy group or a substituted cycloalkoxy group; p is 1, 2 or 3; each of R ^{2 ″} and R ^{2 ″ ″} represents a substituted alkoxy group (except in the case where the pyridine ring is substituted by a benzoyl group at the 3-position and the pyridine ring contains a CF ₃ group in at least one of the 2,6-positions )

(7) A benzoylpyridine derivative or a salt thereof according to the above (5) or (6), wherein the halogen atom represented by X is a fluorine atom or a chlorine atom.

(8) A benzoylpyridine derivative or a salt thereof according to the above (5) or (6), wherein n is 3 or 4.

(9) A benzoylpyridine derivative or a salt thereof according to (5) or (6) above, where, when n is 1 or 2, the halogen atom represented by X is a fluorine atom or a chlorine atom.

(10) A benzoylpyridine derivative or a salt thereof according to the above (5), represented by the formula (I ″ ″)

where X represents a halogen atom, an alkoxy group, an alkyl group, a CF ₃ group or an alkylthio group; n is 1, 2 or 3; R ¹ represents an alkyl group; R ^{2 '} represents an alkoxy group; p is 1, 2 or 3; and each of R ^{2 ″} and R ^{2 ″ ″} represents an alkoxy group.

(11) A benzoylpyridine derivative or a salt thereof according to the above (10), represented by the formula (I ″ ″)

where X represents a halogen atom, an alkoxy group, an alkyl group, a CF ₃ group or an alkylthio group; n is 1, 2 or 3; R ¹ represents an alkyl group; R ^{2 '} represents an alkoxy group; p is 1, 2 or 3; and each of R ^{2 ″} and R ^{2 ″ ″} represents an alkoxy group (except when the pyridine ring is substituted with a benzoyl group at the 3-position and the pyridine ring contains a CF ₃ group in at least one of the 2,6-positions )

(12) A benzoylpyridine derivative or a salt thereof according to the above (8), represented by the formula (I ″ ″ ″)

where B is —CX ⁴ = when A is —N =; B is —N = when A is —CH =; each of X ¹ and X ² that are independent of each other, represents a halogen atom, an alkoxy group, an alkyl group, a CF ₃ group or an alkylthio group; X ³ represents a hydrogen atom, a halogen atom, an alkoxy group, an alkyl group, a CF ₃ group or an alkylthio group; X ⁴ represents a hydrogen atom, a halogen atom, an alkoxy group, an alkyl group, a CF ₃ group or an alkylthio group; R ¹ represents an alkyl group; R ^{2 '} represents an alkoxy group; p is 1, 2 or 3; and each of R ^{2 ″} and R ^{2 ″ ″} represents an alkoxy group.

(13) A benzoylpyridine derivative or a salt thereof according to the above (8), represented by the formula (I ″ ″ ″)

where B is —CX ⁴ = when A is —N =; B is —N = when A is —CH =; each of X ¹ and X ² that are independent of each other, represent a halogen atom, an alkoxy group, an alkyl group, a CF ₃ group or an alkylthio group; X ³ represents a hydrogen atom, a halogen atom, an alkoxy group, an alkyl group, a CF ₃ group or an alkylthio group; X ⁴ represents a hydrogen atom, a halogen atom, an alkoxy group, an alkyl group, a CF ₃ group or an alkylthio group; R ¹ represents an alkyl group; R ^{2 '} represents an alkoxy group; p is 1, 2 or 3; and each of R ^{2 ″} and R ^{2 ″ ″} represents an alkoxy group (except where A represents —CH═ and B represents —N =, and X ² represents a CF ₃ group).

A compound represented by formula (I) or a salt thereof can be prepared according to a known method for preparing a similar compound (such as the method disclosed in WO 96/17829). However, as preferred methods, you can specify methods 1-3, presented in the following diagrams. Here, X, R ¹ , R ² , n and m in the formulas have the above meanings. One of the substituents represented by M ¹ in the formula (II) and M ² in the formula (III) represents a cyano group, and the other represents a metal atom, or a mixed salt thereof; the substituent represented by W in the formula (V) represents a halogen atom or a trifluoromethanesulfonyloxy group; one of the substituents represented by M ³ in formula (VI) and M ⁴ in formula (VII) represents a formyl group, and the other represents a metal atom or its mixed salt.

Method 1

A method for producing a compound represented by formula (I), which comprises carrying out a condensation reaction of a compound represented by formula (II) and a compound represented by formula (III) to obtain an imino compound represented by formula (VIII)

where X, R ¹ , R ² , n and m are as previously defined, a Z is a metal atom or its mixed salt, and the hydrolysis of the resulting compound.

The metal atom designated by each of M ¹ and M ² in formulas (II) and (III) may be, for example, an atom of a typical metal, such as lithium, magnesium, zinc or copper; or a transition metal atom such as palladium or ruthenium. In addition, instead of a metal atom, a mixed salt of a metal atom can be used.

A compound of formula (II) where M ¹ is a cyano group and a compound of formula (III) where M ² is a cyano group can be prepared in a known manner, such as disclosed in Journal of the Chemical Society, Perkin transactions 1 pages 2323-2326, 1999.

The condensation reaction to obtain the imino compound is carried out in a suitable solvent (an inert solvent such as tetrahydrofuran, diethyl ether, dimethoxyethane, hexane, benzene, toluene, methylene chloride, or mixtures thereof) at a reaction temperature of from -100 to 70 ° C, preferably from -80 up to 30 ° C. This reaction is preferably carried out in an atmosphere of inert gas, for example nitrogen or argon.

The imino compound obtained by the condensation reaction is hydrolyzed in a known manner and converted to the compound represented by formula (I). The hydrolysis reaction can be carried out in the presence of, for example, water, alcohol or a mixture thereof. In method 1, the condensation reaction and the hydrolysis reaction are usually carried out continuously and do not emit any imino compounds. In addition, in order to obtain the compound represented by formula (I) in a high yield, it is preferable to carry out the hydrolysis reaction after the condensation reaction is completely completed.

Method 2

A method of producing a compound represented by formula (I), which comprises carrying out a condensation reaction of a compound represented by formula (IV) and a compound represented by formula (V) to obtain a compound represented by formula (IX)

where X, R ¹ , R ² , n and m are as previously defined, and the implementation of oxidative decyanation in the presence of a base.

The reaction for preparing the compound represented by formula (IX) in the first half of method 2 is usually carried out in the presence of a base, preferably in a solvent. The base that can be used in this reaction may be, for example, lithium hydride, sodium hydride, sodium methoxide, sodium ethoxide or potassium tert-butoxide. The solvent may be, for example, tetrahydrofuran, diethyl ether, benzene, toluene, methylene chloride, chloroform or DMF, or mixtures of these solvents. This reaction is preferably carried out at a temperature of from 0 to 100 ° C. In addition, it is preferably carried out in an atmosphere of inert gas, for example nitrogen or argon. In addition, in cases where it is desired to accelerate the reaction, sodium benzenesulfinate or sodium p-toluenesulfinate can be added.

The oxidative decyanation reaction in the last half of method 2 is carried out in the presence of a base. The base may be, for example, sodium hydride, potassium hydride, sodium carbonate or potassium carbonate. In addition, if necessary, an interfacial catalyst (such as benzyltriethylammonium chloride or tetrabutylammonium hydrogen sulfate) can be used. This reaction is usually carried out in a suitable solvent (such as an inert solvent, such as, for example, methylene chloride, chloroform, 1,2-dichloroethane, benzene, toluene, DMF or DMSO, or in a solvent containing water or mixtures thereof), at a reaction temperature from 0 to 50 ° C.

Method 3

A method for producing a compound represented by formula (I), which comprises reacting a compound represented by formula (VI) and a compound represented by formula (VII) to produce phenylpyridylmethanol represented by formula (X)

(where X, n, m, R ¹ and R ² have the meanings indicated above for formula (I)), and the implementation of the oxidation reaction of the obtained compound.

Each of the metal atoms designated M ³ and M ⁴ in method 3 may be, for example, an atom of a typical metal, such as lithium, magnesium, zinc or copper; or a transition metal atom such as palladium or ruthenium. In addition, instead of a metal atom, a mixed salt of a metal atom can be used.

The compound of formula (VI), where the substituent designated M ³ is a formyl group, and the compound of formula (VII), where the substituent designated M ⁴ is a formyl group, can usually be obtained by a known method, such as the method disclosed in Journal of Organic Chemistry, vol. 57, pages 6847-6852, 1992.

The phenylpyridylmethanol represented by the formula (X) obtained from the compound represented by the formula (VI) and the compound represented by the formula (VII) can be oxidized by known methods using a metal-containing oxidizing agent such as manganese dioxide or chromic acid, the oxidation method according to Suern (Swern) (dimethyl sulfoxide + oxalyl chloride) or an oxidation method using ruthenium (tetrapropylammonium perruthenate + N-methylmorpholine-N-oxide) and converted to the compound represented by formula (I).

The following discloses a method of implementing method 3.

(1) A method for producing a compound represented by formula (I), which comprises reacting a substituted benzaldehyde represented by formula (VI-1)

(where R ¹ , R ² and m are as previously defined), and salts of a substituted pyridine derivative with a metal represented by the formula (VII-1)

(where X is as previously defined, and Z represents a metal atom or its mixed salt) to obtain phenylpyridylmethanol represented by formula (X) and its oxidation.

(2) A method for producing a compound represented by formula (I), which comprises reacting a salt of a substituted benzene derivative with a metal represented by formula (VI-2):

(where R ¹ , R ² and m are as previously defined, and Z represents a metal atom or its mixed salt), and a substituted pyridylaldehyde represented by the formula (VII-2)

(where X have the previously indicated meanings), to obtain phenylpyridylmethanol represented by the formula (X), and its oxidation.

The following are preferred varieties of phenylpyridylmethanol represented by formula (X), which is an intermediate to produce a compound represented by formula (I).

(1) Phenylpyridylmethanol represented by the formula (X ')

where X, n and R ¹ have the meanings given above for formula (I), R ^{2 ′} represents a substituted alkyl group, a substituted alkoxy group, a substituted aryloxy group, a substituted cycloalkoxy group or a hydroxyl group, p is 1, 2 or 3; and R ^{2 ″} represents a substitutable alkoxy group or a hydroxyl group, provided that at least two of R ^{2 ″} and R ^{2 ″} may contain an oxygen atom to form a fused ring (except when the pyridine ring is substituted with a benzoyl group in 2-position; the pyridine ring is substituted with an alkoxy group, a hydroxyl group or a benzyloxy group at the 3-position; and n is 1, p is 1).

(2) Phenylpyridylmethanol according to the above (1), represented by the formula (X ″)

where X represents a halogen atom, a nitro group, a substituted alkoxy group, a substituted aryloxy group, a substituted cycloalkoxy group, a substituted hydrocarbon group, a substituted alkylthio group, a cyano group, a carboxyl group which may be esterified or amidated, or a substituted amino group; n is 1, 2, 3 or 4; R ¹ represents an alkyl group; R ^{2 ″} represents a substituted alkyl group, a substituted alkoxy group, a substituted aryloxy group or a substituted cycloalkoxy group, p is 1, 2 or 3, and each of R ^{2 ″} and R ^{2 ″ ″} represents a substituted alkoxy group.

(3) Phenylpyridylmethanol according to the above (2), wherein X represents a halogen atom, a nitro group, a substituted alkoxy group, a substituted cycloalkoxy group, an alkyl group, a substituted alkylthio group or a substituted amino group.

(4) Phenylpyridylmethanol according to the above (2) or (3), wherein the pyridine ring is substituted with a benzoyl group at the 4-position.

(5) Phenylpyridylmethanol according to the above (1), represented by the formula (X ″ ″)

where X represents a halogen atom, a substituted alkoxy group, an alkyl group, a CF ₃ group or an alkylthio group; n is 1, 2, 3 or 4; R ¹ represents an alkyl group; R ^{2 '} represents a substituted alkyl group, a substituted alkoxy group or a substituted cycloalkoxy group; p is 1, 2 or 3; and each of R ^{2 ″} and R ^{2 ″ ″} represents a substituted alkoxy group.

(6) Phenylpyridylmethanol according to the above (5), represented by the formula (X ″ ″)

where X represents a halogen atom, an alkoxy group, an alkyl group, a CF ₃ group or an alkylthio group; n is 1, 2 or 3; R ¹ represents an alkyl group; R ^{2 '} represents an alkoxy group; p is 1, 2 or 3; and each of R ^{2 ″} and R ^{2 ″ ″} represents an alkoxy group.

(7) Phenylpyridylmethanol according to the above (5) or (6), wherein the pyridine ring is substituted with a benzoyl group at the 4-position.

(8) Phenylpyridylmethanol according to the above (6), represented by the formula (X ″ ″ ″)

where B is —CX ⁴ =, if A is —N =; B is —N = if A is —CH =; each of X ¹ and X ² independently from each other represents a halogen atom, an alkoxy group, an alkyl group, a CF ₃ group or an alkylthio group; X ³ represents a hydrogen atom, a halogen atom, an alkoxy group, an alkyl group, a CF ₃ group or an alkylthio group; X ⁴ represents a hydrogen atom, a halogen atom, an alkoxy group, an alkyl group, a CF ₃ group or an alkylthio group; R ¹ represents an alkyl group; R ^{2 '} represents an alkoxy group; p is 1, 2 or 3; and each of R ^{2 ″} and R ^{2 ″ ″} represents an alkoxy group.

(9) Phenylpyridylmethanol according to the above (8), wherein A is —N =.

In addition, substituents electrophilic or nucleophilic can be further added to the compound represented by formula (I). That is, the compound represented by formula (I) can be converted into the compound represented by formula (Ia) or (Ib), as illustrated in the following scheme. In addition, a radical radical may be introduced into the compound represented by formula (I). Here, in the formula (I-a) E represents an electrophilic reagent, and in the formula (I-b) Nu represents a nucleophilic reagent.

n 'and n' 'have the previously indicated values for n.

The reaction to obtain the compound represented by formula (Ia) varies appropriately depending on the electrophilic agent, and the reaction is usually carried out by known methods or the method presented here. For example, you can use the above method 1. The nucleophilic substitution to obtain the compound represented by formula (I-b), varies appropriately depending on the nucleophilic agent, and the reaction is usually carried out by known methods or the method presented here. For example, in the case of an ethyloxynucleophilic reagent, it is preferable to conduct the reaction in the presence of an inert solvent, such as ethanol or dioxane, toluene or octane, at a reaction temperature of from 0 to 120 ° C for an appropriate period of time. The ethyloxynucleophilic reagent is used in an amount of from 0.1 to 10 molar equivalents, preferably from 0.5 to 5 molar equivalents.

In addition, the compound represented by formula (1-c) (the compound of formula (I), where X represents a halogen atom) can be further converted to the compound represented by formula (I-d) by removal of the halogen substituent as shown in the following scheme. In the reaction illustrated further in the scheme, catalytic hydrogenation, a hydrogen transfer reaction or a metal reduction reaction can be suitably used. In the diagram, Hal represents a halogen atom.

Catalytic hydrogenation can be carried out in the presence of a catalyst in a hydrogen gas atmosphere at normal pressure or at elevated pressure in an appropriate solvent. A catalyst that can be used can be, for example, a catalyst system comprising platinum, palladium, rhodium, ruthenium, nickel or iridium. As the solvent, for example, water, alcohol (such as methanol or ethanol), ethyl acetate, acetic acid, dioxane, ether, benzene or hexane can be used. In this case, the catalyst is used in an amount of from 0.01 to 1.2 moles, based on the compound represented by formula (I-c). In addition, the reaction can be carried out in the presence of a base such as triethylamine or sodium bicarbonate. In addition, a known reduction reaction can be used, such as a hydrogen transfer reaction (for example, using palladium-on-charcoal, ammonium formate as a hydrogen source or sodium dihydrogen phosphate), or a metal reduction reaction (for example, samarium diiodide).

The following are specific examples of the preparation of benzoylpyridine derivatives represented by formula (I) and intermediates for their preparation (the names of the compounds in the preparation examples are based on the IUPAC nomenclature, and the positions of substituents may differ from the positions presented in the tables below).

Production Example 1

Preparation of 3- (2,3,4-trimethoxy-6-methylbenzoyl) -2,6-dichloro-4-trifluoromethylpyridine (compound No. 3)

(a) 14 ml (20 mmol) of n-butyllithium (1.5 M hexane solution) was added dropwise at 0 ° C. to a solution containing 2.9 ml (21 mmol) of diisopropylamine dissolved in 62 ml of tetrahydrofuran, followed by stirring within 30 minutes The solution was cooled to −20 ° C., a solution containing 4.0 g (19 mmol) of 2,6-dichloro-4-trifluoromethylpyridine dissolved in 5 ml of tetrahydrofuran was added to the resulting mixture, followed by stirring for 5 minutes, and added to the resulting a solution containing 3.8 g (18 mmol) of 2,3,4-trimethoxy-6-methylbenzaldehyde dissolved in 7 ml of tetrahydrofuran, followed by stirring for 1.5 hours. 30 ml of water was added to the mixture to complete the reaction, and tetrahydrofuran was distilled off under reduced pressure. Extraction is carried out with ethyl acetate, the organic layer is dried over anhydrous sodium sulfate, filtered and the solvent is distilled off under reduced pressure. The crude product thus obtained was purified by silica gel column chromatography to obtain 6.2 g (81% yield) (2,3,4-trimethoxy-6-methylphenyl) (2,6-dichloro-4-trifluoromethyl-3-pyridyl) methanol (an oily substance of brown color).

(b) 14 g of magnesium dioxide are added to a solution containing 5.4 g of (2,3,4-trimethoxy-6-methylphenyl) (2,6-dichloro-4-trifluoromethyl-3-pyridyl) methanol obtained in step ( a) and toluene dissolved in 140 ml, followed by stirring at the boil under reflux with heating for 6 hours. The mixture was cooled, then filtered and the toluene was distilled off under reduced pressure to obtain 4.4 g (81% yield) of 3- (2,3,4-trimethoxy-6-methylbenzoyl) -2,6-dichloro-4-trifluoromethylpyridine compound No. 3 ; Mp 81-83 ° C).

Production Example 2

Obtaining 3- (2,3,4-trimethoxy-6-methylbenzoyl) -2-chloro-4-trifluoromethylpyridine (compound No. 11) and 3- (2,3,4-trimethoxy-6-methylbenzoyl) -4-trifluoromethylpyridine ( connection No. 7)

2.4 ml (17 mmol) of triethylamine and 0.3 g of 5% palladium-on-carbon are added to a solution containing 3.4 g (8.0 mmol) of 3- (2,3,4-trimethoxy-6-methylbenzoyl ) -2,6-dichloro-4-trifluoromethylpyridine (compound No. 3) obtained in Production Example 1, dissolved in 50 ml of methanol, followed by stirring in a hydrogen atmosphere for 6.5 hours. The mixture was filtered, 50 ml of water was added thereto, and methanol was distilled off under reduced pressure. Extraction is carried out with ethyl acetate, the organic layer is dried over anhydrous sodium sulfate, filtered and the solvent is distilled off under reduced pressure. The crude product thus obtained was purified on a silica gel column chromatography to obtain 1.7 g (55% yield) of 3- (2,3,4-trimethoxy-6-methylbenzoyl) -2-chloro-4-trifluoromethylpyridine (compound No. 11; Mp 110-112 ° C) and 1.1 g (37% yield) 3- (2,3,4-trimethoxy-6-methylbenzoyl) -4-trifluoromethylpyridine (compound No. 7; mp 59- 62 ° C).

Production Example 3

Preparation of 4- (2,3,4-trimethoxy-6-methylbenzoyl) -2,5-dichloro-3-trifluoromethylpyridine (compound No. 90)

(a) 17 ml (25 mmol) of n-butyllithium (1.5 M hexane solution) is added dropwise at 0 ° C. to a solution containing 3.6 ml (25 mmol) of diisopropylamine dissolved in 60 ml of diethyl ether, followed by stirring for 45 minutes The solution was cooled to −78 ° C., a solution containing 6.0 g (24 mmol) of 2,3,6-trichloro-5-trifluoromethylpyridine dissolved in 8 ml of diethyl ether was added to the resulting solution, followed by stirring for 5 minutes, and to the resulting solution was added a solution containing 5.0 g (24 mmol) of 2,3,4-trimethoxy-6-methylbenzaldehyde dissolved in 12 ml of toluene, followed by stirring for 1 hour. 30 ml of water was added to the mixture to complete the reaction, the aqueous layer was extracted with ethyl acetate, and then the organic layer was dried over anhydrous sodium sulfate, filtered and the solvent was distilled off under reduced pressure to obtain (2,3,4-trimethoxy-6-methylphenyl) (2, 3,6-trichloro-5-trifluoromethyl-4-pyridyl) methanol (mp. 131-135 ° C).

(b) 2.7 ml (19 mmol) of triethylamine and 0.9 g of 5% palladium-on-carbon are added to a solution containing (2,3,4-trimethoxy-6-methylphenyl) (2,3,6-trichloro -5-trifluoromethyl-4-pyridyl) methanol obtained in stage (a), dissolved in 200 ml of methanol, followed by stirring in a hydrogen atmosphere for 14 hours. The mixture was filtered, 30 ml of water was added thereto, and methanol was distilled off under reduced pressure. Extraction is carried out with ethyl acetate, the organic layer is dried over anhydrous sodium sulfate, filtered and the solvent is distilled off under reduced pressure. The crude product thus obtained was purified by silica gel column chromatography to obtain 2.38 g (24% yield) (2,3,4-trimethoxy-6-methylphenyl) (2,5-dichloro-3-trifluoromethyl-4-pyridyl) methanol (mp 162-165 ° C).

(c) 14 g of manganese dioxide are added to a solution containing 3.5 g (8.2 mmol) of (2,3,4-trimethoxy-6-methylphenyl) (2,5-dichloro-3-trifluoromethyl-4-pyridyl) methanol obtained in stage (b), dissolved in 100 ml of toluene, followed by stirring at the boil under reflux with heating for 6 hours. The mixture was cooled, then filtered and the toluene was distilled off under reduced pressure. The crude product thus obtained was purified by silica gel column chromatography to obtain 3.1 g (89% yield) 4- (2,3,4-trimethoxy-6-methyl-benzoyl-2,5-dichloro-3-trifluoromethylpyridine (compound No. 90; mp 106-109 ° C).

Production Example 4

Obtaining 3- (4,5-dimethoxy-2-methylbenzoyl) -2-methoxy-4-trifluoromethylpyridine (compound No. 32)

0.9 g (16 mmol) of sodium methoxide is added to a solution containing 1.5 g (4.2 mmol) of 3- (4,5-dimethoxy-2-methylbenzoyl) -2-chloro-4-trifluoromethylpyridine synthesized by the method production example 1 and dissolved in 20 ml of toluene, followed by stirring at the boil under reflux with heating for 4 hours. The mixture was cooled and then 20 ml of water was added thereto to complete the reaction, the aqueous solution was extracted with ethyl acetate, the organic layer was dried over anhydrous sodium sulfate and filtered using a silica gel cake. The solvent was distilled off under reduced pressure to obtain 1.5 g (99% yield) of 3- (4,5-dimethoxy-2-methylbenzoyl) -2-methoxy-4-trifluoromethylpyridine (compound No. 32; mp. 125-127 ° FROM).

Production Example 5

Obtaining 3- [4,5- (methylenedioxy) -2-methylbenzoyl] -2-chloro-4-trifluoromethylpyridine (compound No. 13)

(a) 3.2 ml (62 mmol) of bromine is added dropwise at 0 ° C. to a solution containing 7.0 ml (58 mmol) of 3,4- (methylenedioxy) toluene and 5.5 ml (68 mmol) of pyridine, dissolved in 110 ml of dichloromethane, followed by stirring for 30 minutes, and the temperature was raised to room temperature, followed by stirring for 22 hours. The mixture was washed with an aqueous solution of sodium hydroxide, dried over anhydrous sodium sulfate, filtered and the solvent was distilled off under reduced pressure. The crude product thus obtained was purified on a silica gel column chromatography to obtain 13 g (99% yield) of 2-bromo-4,5- (methylenedioxy) toluene.

(b) 13 ml (20 mmol) of n-butyllithium (1.5 M hexane solution) was added dropwise at -78 ° C to a solution containing 4.0 g (19 mmol) of 2-bromo-4,5- (methylenedioxy ) toluene dissolved in 50 ml of tetrahydrofuran, followed by stirring for 30 minutes, and 1.5 ml (19 mmol) of dimethylformamide was added to the resulting mixture, followed by stirring for 70 minutes. 30 ml of water was added to the mixture to complete the reaction, and tetrahydrofuran was distilled off under reduced pressure. Extraction is carried out with chloroform, the organic layer is dried over anhydrous sodium sulfate, filtered using a silica gel cake, and the solvent is distilled off under reduced pressure to obtain 3.1 g (99% yield) of 2-methyl-4,5- (methylenedioxy) benzaldehyde (T. pl. 84-86 ° C).

(c) Using 1.5 g (8.3 mmol) of 2-chloro-4-trifluoromethylpyridine and 1.4 g (8.2 mmol) of 2-methyl-4,5- (methylenedioxy) benzaldehyde, according to the method of step (a) ) of Production Example 1, 2.1 g (73% yield) of (2-methyl-4,5- (methylenedioxy) phenyl) (2-chloro-4-trifluoromethyl-3-pyridyl) methanol are obtained (mp. 127-130 ° C).

(d) Using 1.5 g (4.3 mmol) of (2-methyl-4,5- (methylenedioxy) phenyl) (2-chloro-4-trifluoromethyl-3-pyridyl) methanol obtained in step (c), and 8.0 g (92 mmol) of manganese dioxide according to the method of step (b) of Production Example 1, 0.3 g (22% yield) of 3- [4,5- (methylenedioxy) -2-methylbenzoyl] -2-chlorine are obtained -4-trifluoromethylpyridine (compound No. 13; mp. 119-122 ° C).

Production Example 6

Obtaining 3- (5-benzyloxy-4-methoxy-2-methylbenzoyl) -2-chloro-4-trifluoromethylpyridine (compound No. 27)

(a) A solution of 2-methoxy-4-methylphenol (6.91 g) in dimethylformamide (15 ml) was added dropwise to a suspension of sodium hydride (2.4 g) in dimethylformamide (20 ml) under ice cooling, followed by stirring for 30 minutes. To the resulting dimethyl foramide (15 ml) solution of benzyl bromide (9.41 g) was added dropwise and a catalytic amount of tetrabutylammonium bromide was added to the resulting mixture, followed by stirring at the same temperature for 30 minutes. The temperature was raised to room temperature and stirring was continued overnight. The reaction solution was poured into water (250 ml) and extracted with ethyl acetate (100 ml) three times. The ethyl acetate phase is washed with water (100 ml) three times and then washed with an aqueous solution of sodium chloride (100 ml). After drying over magnesium sulfate, the solvent was distilled off under reduced pressure, the residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain 11.4 g of 4-benzyloxy-3-methoxytoluene (mp. 38-39 ° C) quantitatively, and The structure of the product is confirmed using a nuclear magnetic resonance spectrum.

(b) 4-benzyloxy-3-methoxytoluene (8.0 g) was dissolved in dimethylformamide (30 ml), and a dimethylformamide solution (15 ml) of N-bromosuccinimide (6.36 g) was added dropwise, followed by stirring at room temperature during the night. The reaction solution was poured into ice water (400 ml), and the precipitated crystals were collected by filtration, washed with water and dried overnight to obtain 10.64 g of 4-benzyloxy-2-bromo-5-methoxytoluene (mp. . 110-111 ° C) is practically quantitative, and the structure of this compound is confirmed using the spectrum of nuclear magnetic resonance.

(c) A hexane solution (17 ml) of n-butyllithium was added dropwise to a tetrahydrofuran solution (190 ml) of 4-benzyloxy-2-bromo-5-methoxytoluene (7.83 g) at -78 ° C for 20 min followed by stirring at the same temperature for 1 hour. To the resulting dropwise tetrahydrofuran solution (10 ml) was added dimethylforms and (3.73 g) at -78 ° C, followed by stirring at the same temperature for 1 hour. The temperature was gradually raised to room temperature, and stirring was continued overnight. The reaction solution was poured into an aqueous solution of ammonium chloride (200 ml) and extracted with ethyl acetate (150 ml) twice. The ethyl acetate phase was washed with an aqueous solution of sodium chloride (100 ml) twice, dried over magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain 3.14 g (48% yield) of 5-benzyloxy-4-methoxy-2-methylbenzaldehyde (mp. 107-109 ° C), and its structure was confirmed using the spectrum of nuclear magnetic resonance.

(d) A hexane solution (11.4 ml) of n-butyllithium was added dropwise to a tetrahydrofuran solution (45 ml) of diisopropylamine (2.81 g) at 0 ° C., followed by stirring for 1 hour to obtain a tetrahydrofuran solution of lithium diisopropylamide. The solution was cooled to -50 ° C and a tetrahydrofuran solution (7.5 ml) of 2-chloro-4-trifluoromethylpyridine (2.81 g) was gradually added to the resulting solution, followed by stirring at the same temperature for 30 minutes. The solution was cooled to -78 ° C and a tetrahydrofuran solution (37.5 ml) of 5-benzyloxy-4-methoxy-2-methylbenzaldehyde (3.97 g) was gradually added to the resulting solution, followed by stirring at the same temperature for 1 hour. A saturated aqueous solution of ammonium chloride (50 ml) was added to the resultant, the temperature was raised to room temperature, the mixture was poured into a saturated aqueous solution of sodium bicarbonate (50 ml), and extracted with ethyl acetate (150 ml) twice. The ethyl acetate phase was washed with an aqueous solution of sodium chloride (100 ml), dried over magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain 6.48 g (96% yield) (5-benzyloxy-4-methoxy-2-methylphenyl) (2-chloro-4-trifluoromethyl-3-pyridyl) methanol in the form of a red-yellow oily substance, the structure of which is confirmed by the spectrum of nuclear magnetic resonance.

(e) (5-benzyloxy-4-methoxy-2-methylphenyl) (2-chloro-4-trifluoromethyl-3-pyridyl) methanol (5.9 g) is dissolved in a mixed solvent consisting of anhydrous methylene chloride (50 ml) and acetonitrile (5 ml), and tetrapropylammonium perruthenate (95 mg), N-methylmorpholine-N-oxide (2.38 g) and molecular sieves 4A (6.8 g) were successively added to the resulting mixture, followed by stirring under argon at room temperature in for three nights. The reaction mixture was distilled off under reduced pressure, the residue thus obtained was suspended in methylene chloride and filtered through celite; the residue is suitably washed with methylene chloride (200 ml). The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain 4.93 g (84% yield) of 3- (5-benzyloxy-4-methoxy-2-methylbenzoyl) -2-chloro- 4-trifluoromethylpyridine (compound No. 27; mp 116-117 ° C), the structure of which is confirmed by the spectrum of nuclear magnetic resonance.

Production Example 7

Obtaining 3- (2,3,4-trimethoxy-6-methylbenzoyl) -2-methylthio-4-trifluoromethylpyridine (compound No. 50)

Sodium methanethiolate (0.32 g) was added to a dimethylformamide solution (15 ml) 0.9 g of 3- (2,3,4-trimethoxy-6-methylbenzoyl) -2-chloro-4-trifluoromethylpyridine (compound No. 11) at room temperature followed by stirring for 1 hour. The mixture was poured into water (50 ml) and extracted with ethyl acetate. The ethyl acetate phase was dried over sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain 0.54 g (58% yield) 3- (2,3,4-trimethoxy-6- methylbenzoyl) -2-methylthio-4-trifluoromethylpyridine (compound No. 50; pale yellow oily substance), the structure of which is confirmed by the nuclear magnetic resonance spectrum.

Production Example 8

Preparation of 5- (2,3,4-trimethoxy-6-methylbenzoyl) -3-acetyl-2, 6-dichloro-4-trifluoromethylpyridine (compound No. 62)

(a) 9.6 ml (14 mmol) of n-butyllithium (1.5 M hexane solution) was added dropwise to a tetrahydrofuran (16 ml) solution of 2.0 ml (14 mmol) of diisopropylamine at 0 ° C., followed by stirring for 30 minutes. The solution was cooled to -50 ° C, to which was added a tetrahydrofuran (11 ml) solution of 2.9 g (7 mmol) (2,3,4-trimethoxy-6-methylphenyl) (2,6-dichloro-4-trifluoromethyl-3 -pyridyl) methanol, followed by stirring for 30 minutes, then the solution is cooled to -78 ° C and an excess of acetaldehyde is added to the resulting mixture, followed by stirring for 2 hours. 30 ml of water was added to the mixture to complete the reaction, and tetrahydrofuran was distilled off under reduced pressure. The mixture was extracted with ethyl acetate, the organic layer was dried over anhydrous sodium sulfate, filtered and the solvent was distilled off under reduced pressure. The crude product thus obtained was purified on a silica gel column chromatography to obtain 2.5 g (78% yield) (2,3,4-trimethoxy-6-methylphenyl) (2,6-dichloro-5- (1-hydroxyethyl) - 4-trifluoromethyl-3-pyridyl) methanol.

(b) 10 g of manganese dioxide are added to a toluene (80 ml) solution of 2.3 g (5 mmol) (2,3,4-trimethoxy-6-methylphenyl) (2,6-dichloro-5- (1-hydroxyethyl) -4-trifluoromethyl-3-pyridyl) methanol obtained in stage (a), followed by stirring at the boil under reflux with heating for 1 hour. The reaction solution was cooled to room temperature, then filtered, and toluene was distilled off under reduced pressure. The crude product thus obtained was purified by silica gel column chromatography to obtain 1.5 g (66% yield) 5- (2,3,4-trimethoxy-6-methylbenzoyl) -3-acetyl-2,6-dichloro-4- trifluoromethylpyridine (compound No. 62; mp 109-112 ° C).

Production Example 9

Preparation of 4- (2,3,4-trimethoxy-6-methylbenzoyl) -2-chloro-3-trifluoromethyl-5-methoxypyridine (compound No. 123)

(a) 70.0 ml (106 mmol) of n-butyllithium (1.5 M hexane solution) was added dropwise to a solution of 15.0 ml (107 mmol) of diisopropylamine in diethyl ether (120 ml) at 0 ° C, followed by stirring within 1 hour. The solution was cooled to −78 ° C., a solution of 22.1 g (102 mmol) of 2,3-dichloro-5-trifluoromethylpyridine in diethyl ether (10 ml) was added thereto, followed by stirring for 30 minutes, and then a toluene solution was added to the resulting (40 ml) 21.0 g (100 mmol) of 2,3,4-trimethoxy-6-methylbenzaldehyde, followed by stirring for 2 hours. To the mixture was added 30 ml of water to complete the reaction, the aqueous layer was extracted with ethyl acetate, and then the organic layer was dried over anhydrous sodium sulfate, filtered and the solvent was distilled off under reduced pressure. The crude product thus obtained was purified by silica gel column chromatography to obtain 24.8 g (58% yield) (2,3,4-trimethoxy-6-methylphenyl) (2,3-dichloro-5-trifluoromethyl-4-pyridyl) methanol (mp. 95-98 ° C).

(b) 2.1 g of 5% palladium-on-carbon are added to a methanol solution (200 ml) of 24.8 g (58.1 mmol) of (2,3,4-trimethoxy-6-methylphenyl) (2,3- dichloro-5-trifluoromethyl-4-pyridyl) methanol obtained in step (a) and 9.50 ml (68.2 mmol) of triethylamine, followed by stirring in a hydrogen atmosphere for 4 hours. The mixture was filtered, 50 ml of water was added thereto, and methanol was distilled off under reduced pressure. The aqueous layer was extracted with ethyl acetate and the organic layer was dried over anhydrous sodium sulfate, filtered and the solvent was distilled off under reduced pressure. The crude product thus obtained was purified by silica gel column chromatography to obtain 15.9 g (70% yield) (2,3,4-trimethoxy-6-methylphenyl) (3-chloro-5-trifluoro-methyl-4-pyridyl) methanol (mp. 102-105 ° C).

(c) 45 g of manganese dioxide are added to a toluene solution (220 ml) of 15.9 g (40.6 mmol) of (2,3,4-trimethoxy-6-methylphenyl) (3-chloro-5-trifluoromethyl-4-pyridyl ) methanol obtained in stage (b), followed by stirring at the boil under reflux with heating for 2 hours. The mixture was filtered and the solvent was distilled off under reduced pressure to obtain 14.9 g (94% yield) of 4- (2,3,4-trimethoxy-6-methylbenzoyl) -3-chloro-5-trifluoromethylpyridine (compound No. 102; mp. . 75-77 ° C).

(d) 16.4 g (304 mmol) of sodium methoxide are added to a toluene solution (150 ml) of 18.5 g (47.5 mmol) of 4- (2,3,4-trimethoxy-6-methylbenzoyl) -3-chloro -5-trifluoromethylpyridine obtained in step (c) and 16.6 ml (95.4 mmol) of hexamethylphosphoric triamide, followed by stirring under reflux with heating for 30 minutes. Water was added to the mixture to complete the reaction, the aqueous layer was extracted with ethyl acetate and the organic layer was dried over anhydrous sodium sulfate, filtered and the solvent was distilled off under reduced pressure. The crude product thus obtained was purified by silica gel column chromatography to obtain 11.7 g (64% yield) of 4- (2,3,4-trimethoxy-6-methylbenzoyl) -3-methoxy-5-trifluoromethylpyridine (compound No. 122; Mp 103-106 ° C).

(e) 6.1 g (28 mmol) of m-chloroperbenzoic acid (m-CPBA) is added to a chloroform solution (100 ml) 5.6 g (15 mmol) of 4- (2,3,4-trimethoxy-6-methylbenzoyl ) -3-methoxy-5-trifluoromethylpyridine (compound No. 122) at 0 ° C, followed by stirring at room temperature for 18 hours. The reaction solution was washed with saturated aqueous sodium hydroxide and the solvent was distilled off under reduced pressure to obtain 5.8 g (99% yield) of 4- (2,3,4-trimethoxy-6-methylbenzoyl) -3-methoxy-5-trifluoromethylpyridin-N -oxide (mp. 128-134 ° C).

(f) 1.8 ml (19 mmol) of phosphorus oxychloride is added to 4 ml of toluene and 8 ml of dimethylformamide at 0 ° C, followed by stirring for 10 minutes, and 4.0 g (10 mmol) of 4- are added to the resulting (2, 3,4-trimethoxy-6-methylbenzoyl) -3-methoxy-5-trifluoromethylpyridine-N-oxide, followed by stirring for 20 minutes. Stirring was carried out at room temperature for 2 hours, and then the reaction solution was poured into ice water to complete the reaction. The aqueous layer was extracted with ethyl acetate, then the organic layer was dried over anhydrous sodium sulfate, filtered and the solvent was distilled off under reduced pressure. The crude product thus obtained was purified on a silica gel column chromatography to obtain 3.57 g (85% yield) of 4- (2,3,4-trimethoxy-6-methylbenzoyl) -2-chloro-3-trifluoromethyl-5-methoxypyridine ( compound No. 123; mp 117-119 ° C).

Production Example 10

Preparation of 4- (2,3,4-trimethoxy-6-methylbenzoyl) -2-bromo-3-trifluoromethyl-5-methoxypyridine (compound No. 124)

Using 7.2 g (18 mmol) of 4- (2,3,4-trimethoxy-6-methylbenzoyl) -3-methoxy-5-trifluoromethylpyridin-N-oxide, 7 ml of toluene, 17 ml of dimethylformamide and 10 g (35 mmol) ) phosphorus bromide, by the method of Production Example 9 of step (f), 4.1 g (49% yield) of 4- (2,3,4-trimethoxy-6-methylbenzoyl) -2-bromo-3-trifluoromethyl-5-methoxypyridine are obtained (compound No. 124; mp 145-147 ° C).

Production Example 11

Preparation of 4- (2,3,4-trimethoxy-6-methylbenzoyl) -2,3,5-trichloropyridine (compound No. 186)

(a) 17.2 ml (26.7 mmol) of n-butyllithium (1.56 M hexane solution) was added dropwise to a solution of 2.7 g (26.7 mmol) of diisopropylamine in diethyl ether (20 ml) at 0 ° With subsequent stirring for 1 hour. The solution was cooled to −78 ° C., 4.8 g (26.7 mmol) of 2,3,5-trichloropyridine toluene solution was added dropwise to the solution, and then 5.0 g (24.0 mmol) of toluene solution was added dropwise. ) 2,3,4-trimethoxy-6-methylbenzaldehyde, followed by stirring for 30 minutes. The temperature was brought to room temperature and stirring was further carried out for 1 hour. 30 ml of water was added to the mixture to complete the reaction, and ethyl acetate was added to extract. The organic layer was dried over anhydrous sodium sulfate, filtered and the solvent was distilled off under reduced pressure. The crude product thus obtained was purified on a silica gel column chromatography to obtain 6.7 g (72% yield) of amorphous (2,3,4-trimethoxy-6-methylphenyl) (2,3,5-trichloro-4-pyridyl) methanol .

(b) 16.2 g of manganese dioxide are added to a toluene solution (180 ml) of 5.6 g of (2,3,4-trimethoxy-6-methylphenyl) (2,3,5-trichloro-4-pyridyl) methanol obtained in step (a), followed by stirring at the boil under reflux with heating for 3 hours. After the mixture was cooled, it was filtered and the solvent was distilled off under reduced pressure to obtain 4.7 g (87% yield) of 4- (2,3,4-trimethoxy-6-methylbenzoyl) -2,3,5-trichloropyridine (compound No. 186; mp 60-61 ° C).

Production Example 12

Preparation of 4- (2,3,4-trimethoxy-6-methylbenzoyl) -3,5-dichloropyridine (compound No. 191)

4.6 g (6.9 mmol) of triethylamine and 1.8 g of 10% palladium-on-charcoal are added to a methanol solution (280 ml) 17.8 g (4.6 mmol) of 4- (2,3,4- trimethoxy-6-methylbenzoyl) -2,3,5-trichloropyridine (compound No. 186), followed by stirring in a hydrogen atmosphere at room temperature for 7 hours. The mixture was filtered and the solvent was distilled off under reduced pressure. The crude product thus obtained was purified on a silica gel column chromatography to obtain 11.6 g (72% yield) of 4- (2,3,4-trimethoxy-6-methylbenzoyl) -3,5-dichloropyridine (compound No. 191; T. pl. 109-111 ° C).

Production Example 13

Preparation of 4- (2,3,4-trimethoxy-6-methylbenzoyl) -3-chloro-5-methoxypyridine (compound No. 244)

5.0 g (2.8 mmol) of hexamethylphosphoric triamide and 1.1 g (2.1 mmol) of sodium methoxide are added to a toluene solution (60 ml) 5.0 g (1.4 mmol) of 4- (2,3,4 -trimethoxy-6-methylbenzoyl) -3,5-dichloropyridine (compound No. 191), followed by stirring at the boil under reflux with heating for 5 hours. After the mixture is cooled, 50 ml of water are added to it to complete the reaction, and ethyl acetate is added to the resulting mixture to extract. The organic layer was dried over anhydrous sodium sulfate, filtered and the solvent was distilled off under reduced pressure. The crude product thus obtained was purified by silica gel column chromatography to obtain 3.4 g (yield 69%) of 4- (2,3,4-trimethoxy-6-methylbenzoyl) -3-chloro-5-methoxypyridine (compound No. 244; pale yellow oily substance).

Production Example 14

Preparation of 4- (2,3,4-trimethoxy-6-methylbenzoyl) -2,3-dichloro-5-methoxypyridine (compound No. 193)

(a) A chloroform (60 ml) solution of 3.4 g (1 mmol) of 4- (2,3,4-trimethoxy-6-methylbenzoyl) -3-chloro-5-methoxypyridine (compound No. 244) was cooled with ice to obtain 4.1 g (1.6 mmol) of m-chloroperbenzoic acid are added, followed by stirring under ice-cooling for 2 hours, and stirring is continued at room temperature for 2 hours. To the mixture was added 30 ml of a 0.5 mol / L aqueous solution of sodium hydroxide to complete the reaction, the organic layer was dried over anhydrous sodium sulfate, filtered and the solvent was distilled off under reduced pressure to obtain 3.5 g (85% yield) 4- (2, 3,4-trimethoxy-6-methylbenzoyl) -3-chloro-5-methoxypyridine-N-oxide (mp. 160-166 ° C).

(b) 5 ml of dimethylformamide was added to 2.5 ml of toluene, the mixture was cooled with ice and 1.3 ml (1.4 mmol) of phosphorus oxychloride was added dropwise thereto. The mixture was stirred under ice-cooling for 10 minutes, 2.5 g (0.7 mmol) of 4- (2,3,4-trimethoxy-6-methylbenzoyl) -3-chloro-5-methoxypyridine-N-oxide were added to the resulting mixture. . After the mixture was stirred under ice-cooling for 30 minutes, the temperature was brought to room temperature, followed by stirring for 2 hours. To the mixture was added 30 ml of water to complete the reaction, and ethyl acetate was added to the resulting mixture to extract. The organic layer was dried over anhydrous sodium sulfate, filtered and purified on a silica gel column chromatography to give 2.0 g (76% yield) 4- (2,3,4-trimethoxy-6-methylbenzoyl) -2,3-dichloro-5 -methoxypyridine (compound No. 193; mp 98-99 ° C).

Production Example 15

Obtaining 4- (2,3,4-trimethoxy-6-methylbenzoyl) -2-bromo-3-chloro-5-methoxypyridine (compound No. 245)

5 ml of dimethylformamide was added to 2.5 ml of toluene, the mixture was cooled with ice and 0.7 g (0.2 mmol) of phosphorus oxybromide was added dropwise thereto. After the mixture was stirred under ice cooling for 10 minutes, 0.42 g (0.1 mmol) of 4- (2,3,4-trimethoxy-6-methylbenzoyl) -3-chloro-5-methoxypyridine- was added to the resulting mixture. N-oxide obtained in Production Example 14 (a). After the mixture was stirred under ice-cooling for 30 minutes, the temperature was brought to room temperature, followed by stirring for 2 hours. 10 ml of water was added to the mixture to complete the reaction, and ethyl acetate was added to the resulting mixture to effect extraction. The organic layer was dried over anhydrous sodium sulfate, filtered and purified on a silica gel column chromatography to obtain 0.32 g (65% yield) 4- (2,3,4-trimethoxy-6-methylbenzoyl) -2-bromo-3-chloro -5-methoxypyridine (compound No. 245; mp. 97-99 ° C).

Production Example 16

Preparation of 4- (2,3,4-trimethoxy-6-methylbenzoyl) -3-bromo-5-methylpyridine (compound No. 228)

(a) 57.0 ml (88.9 mmol) of n-butyllithium (1.56 M hexane solution) was added dropwise to a solution of 12.5 ml (89.2 mmol) of diisopropylamine in diethyl ether (110 ml) at 0 ° C followed by stirring for 60 minutes The solution was cooled to -78 ° C, to the resulting solution was added toluene (80 ml) solution of 20 g (85 mmol) of 3,5-dibromopyridine, followed by stirring for 5 min, and then to the resulting solution was added toluene (50 ml) solution 21.0 g (100 mmol) of 2,3,4-trimethoxy-6-methylbenzaldehyde, followed by stirring for 2 hours. 50 ml of water was added to the mixture to complete the reaction, the aqueous layer was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate, filtered and the solvent was distilled off under reduced pressure. The crude product thus obtained was purified by silica gel column chromatography to obtain 11.8 g (31% yield) (2,3,4-trimethoxy-6-methylphenyl) (3,5-dibromo-4-pyridyl) methanol (yellow oily substance).

(b) Tetrahydrofuran (15 ml) solution of 2.0 g (4.6 mmol) of (2,3,4-trimethoxy-6-methylphenyl) (3,5-dibromo-4-pyridyl) methanol obtained in step (a) ), cooled to −78 ° C., 6.0 ml (9.4 mmol) of n-butyllithium (1.56 M hexane solution) was added dropwise thereto, followed by stirring for 5 minutes, and 0.5 was added to the resulting ml (8.0 mmol) of methyl iodide, followed by stirring for 2.5 hours. 20 ml of water are added and tetrahydrofuran is distilled off under reduced pressure. The aqueous layer was extracted with ethyl acetate, the organic layer was dried over anhydrous sodium sulfate, filtered and the solvent was distilled off under reduced pressure. The crude product thus obtained was purified by silica gel column chromatography to obtain 0.44 g (25% yield) of (2,3,4-trimethoxy-6-methylphenyl) (3-bromo-5-methyl-4-pyridyl) methanol.

(c) 3 g of manganese dioxide is added to a toluene (30 ml) solution of 0.43 g (1.1 mmol) (2,3,4-trimethoxy-6-methylphenyl) (3-bromo-5-methyl-4-pyridyl ) methanol obtained in stage (b), followed by stirring at the boil under reflux with heating for 2 hours. The mixture was filtered, the solvent was distilled off under reduced pressure, and the crude product thus obtained was purified on a silica gel column chromatography to obtain 0.23 g (54%) 4- (2,3,4-trimethoxy-6-methylbenzoyl) -3- bromo-5-methylpyridine (compound No. 228; mp 88-93 ° C).

Production Example 17

Obtaining 3- (2,3,4-trimethoxy-6-methylbenzoyl) -2,6-dichloro-4-methylpyridine (compound No. 320)

(a) Synthesis of 3-cyano-2,6-dichloro-4-methylpyridine

A mixture of 4.76 g (32 mmol) of 3-cyano-2,6-dihydroxy-4-methylpyridine and 26 g (133 mmol) of phenylphosphoric acid dichloride was stirred at 150 ° C. for 2 days. The reaction mixture was poured into ice water (200 ml) and filtered with celite, followed by washing with toluene (100 ml). The aqueous layer was extracted twice with ethyl acetate (100 ml) and combined with the organic layer, followed by washing with water (100 ml) (twice) and a saturated aqueous solution of sodium chloride (100 ml), dried over magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain 5.45 g of pale yellow crystals of 3-cyano-2,6-dichloro-4-methylpyridine. ¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.59 (s, 3H), 7.28 (s, 1H).

(b) Synthesis of 2,6-dichloro-3-formyl-4-methylpyridine

1.54 g (8.23 mmol) of 3-cyano-2,6-dichloro-4-methylpyridine was dissolved in methylene chloride (40 ml), cooled to -70 ° C, and then toluene solution (1M, 10 ml) was slowly added dropwise. ) diisobutylaluminum hydride. After stirring at -78 ° C for 15 minutes, the temperature of the liquid was raised to room temperature and stirring was continued overnight. Since the starting materials were not completely consumed, the liquid was again cooled to −78 ° C., toluene solution of diisobutylaluminum hydride was again added and stirring was continued at −78 ° C. for 15 minutes and at room temperature overnight. The reaction mixture was poured into 1N. hydrochloric acid solution and was extracted three times with methylene chloride (50 ml). The methylene chloride layer was washed successively with saturated sodium bicarbonate (100 ml), saturated aqueous sodium chloride (100 ml) and dried over magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain 0.81 g of 2,6-dichloro-3-formyl-4-methylpyridine. ¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.60 (s, 3H), 7.20 (s, 1H), 10.52 (s, 1H).

(c) Synthesis of (2,3,4-trimethoxy-6-methylphenyl) (2,6-dichloro-4-methyl-3-pyridyl) methanol (Intermediate No. 302)

A solution of 3,4,5-trimethoxy-2-bromotoluene (1.53 g, 5.9 mmol) in tetrahydrofuran (25 ml) was cooled to -78 ° C and n-BuLi (1.5 M solution in hexane) was added dropwise. , 4 ml), followed by stirring at the same temperature for 40 minutes to obtain 2,3,4-trimethoxy-6-methylphenyl lithium. Then, a solution of 2,6-dichloro-3-formyl-4-methylpyridine (0.93 g, 4.9 mmol) in tetrahydrofuran (5 ml) was added dropwise thereto, followed by stirring at -78 ° C for 1 hour. To complete the reaction, a saturated aqueous solution of ammonium chloride (15 ml) was added and the temperature of the reaction mixture was raised to room temperature, then the reaction mixture was poured into a saturated solution of sodium bicarbonate and was extracted twice with ethyl acetate (100 ml). The ethyl acetate layer was washed with a saturated aqueous solution of sodium chloride (100 ml), dried over magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (hexane-ethyl acetate) to obtain 0.73 g of a pale yellow oily (2,3,4-trimethoxy-6-methylphenyl) (2,6-dichloro-4-methyl-3-pyridyl) methanol. ¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.20 (s, 3H), 2.41 (s, 3H), 3.46 (s, 3H), 3.77 ( s, 3H), 3.80 (s, 3H), 6.26 (d, J = 6.4 Hz, 1H), 6.46 (s, 1H), 7.03 (s, 1H).

(d) Synthesis of 3- (2,3,4-trimethoxy-6-methylbenzoyl) -2,6-dichloro-4-methylpyridine

1.06 g (2.85 mmol) of (2,3,4-trimethoxy-6-methylphenyl) (2,6-dichloro-4-methyl-3-pyridyl) methanol was dissolved in toluene (50 ml) and 4 was added. 23 g (purity: 88%, 42.8 mmol) of manganese dioxide, followed by heating for 5 hours at the boiling temperature under reflux. The liquids were allowed to cool and the reaction mixture was filtered through celite, then the residue was washed with ethyl acetate (100 ml). The filtrate and wash solution were combined and the solvent was distilled off under reduced pressure, followed by purification by silica gel column chromatography (hexane-ethyl acetate), so as to obtain 0.81 g of a pale yellow oily 3- (2,3,4-trimethoxy-6-methylbenzoyl) -2 6-dichloro-4-methylpyridine. ¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.31 (s, 3H), 2.45 (s, 3H), 3.32 (s, 3H), 3.73 ( s, 3H), 3.88 (s, 3H), 6.56 (s, 1H), 7.18 (s, 1H).

Production Example 18

Preparation of 3- (2,3,4-trimethoxy-6-methylbenzoyl) -2,5-dichloro-4-methylpyridine (Compound No. 321)

(a) Synthesis of 2-amino-3-bromo-5-chloropyridine

25.34 g (197 mmol) of 2-amino-5-chloropyridine and 16.16 g (197 mmol) of sodium acetate were dissolved in 120 ml of acetic acid and heated to 43 ° C, then added dropwise over 1.5 hours at a temperature of 43-45 ° C. 31.5 g (10.2 ml, 197 mmol) of bromine in acetic acid (10 ml). The reaction mixture was allowed to cool, and then it was poured into ice water, the solution was made slightly alkaline (pH 8-9) by adding 1 N. sodium hydroxide (200 ml) and then solid sodium hydroxide and was extracted with 100 ml of ethyl acetate (5 times). The ethyl acetate layers were combined, washed twice with 100 ml of a 10% aqueous solution of sodium sulfite and 100 ml of a saturated aqueous solution of sodium chloride, dried over sodium sulfate and filtered. The solvent was distilled off under reduced pressure to obtain 40.0 g of crude crystals of 2-amino-3-bromo-5-chloropyridine.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 4.98 (broad, 2H), 7.67 (d, J = 2.0 Hz, 1H), 7.97 (d , J = 2.0 Hz, 1H).

(b) Synthesis of 3-bromo-5-chloro-2-hydroxypyridine

40.0 g of crude crystals of 2-amino-3-bromo-5-chloropyridine were dissolved in a solution of concentrated hydrochloric acid (52 ml) in water (326 ml) and cooled in an ice-sodium chloride bath. While maintaining the temperature of the solution below -1 ° C, an aqueous solution (109 ml) of 13.6 g of sodium nitrite (purity 98%, 193 mmol) was gradually added dropwise over 80 minutes, and the reaction mixture was stirred for 20 minutes at 0 ° C. and then overnight at room temperature. The resulting crystals were collected by filtration, washed with 100 ml of water, and then 100 ml of hexane and dried at 40 ° C under reduced pressure to obtain 28.86 g of crude crystals of 3-bromo-5-chloro-2-hydroxypyridine.

(c) Synthesis of 3-bromo-2,5-dichloropyridine

28.86 g of crude crystals of 3-bromo-5-chloro-2-hydroxypyridine was dissolved in 35 ml of dimethylformamide and 31.7 g (19.3 ml) of phosphorus oxychloride was gradually added dropwise over 4 hours. The reaction mixture was heated to 70 ° C and stirred at the same temperature for 3 days. After the mixture was allowed to cool, it was poured into ice water (500 ml) and the resulting crystals were collected by filtration, washed sufficiently with 300 ml of water and dried at room temperature and reduced pressure for 8 hours and (after slightly noticeable sublimation) at atmospheric pressure for 1 week to obtain 21.33 g of crude crystals of 3-bromo-2,5-dichloropyridine.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 7.95 (d, J = 2.0 Hz, 1H), 8.32 (d, J = 2.0 Hz, 1H) .

(d) Synthesis of 2,5-dichloro-3-formylpyridine

10.0 g (44.1 mmol) of 3-bromo-2,5-dichloropyridine in anhydrous diethyl ether (250 ml) was cooled to -78 ° C in an argon atmosphere, and 29.4 ml of n-butyllithium was gradually added dropwise (1 5 M solution in hexane, 44.1 mmol). The resulting mixture was stirred at -78 ° C for 1 hour. To the resulting solution of 2,5-dichloro-3-pyridyllithium, 3.27 g (44.1 mmol) of ethyl formate in 20 ml of anhydrous diethyl ether was gradually added dropwise, and the resulting mixture was stirred at -78 ° C for 2 hours. After confirming the completion of the reaction by TLC, the reaction was completed by adding 23 ml of a saturated aqueous solution of ammonium chloride to the reaction mixture, and then 200 ml of water. After warming to room temperature, the reaction mixture was extracted 3 times with 150 ml of ethyl acetate and the ethyl acetate layers were combined, washed with 200 ml of a saturated aqueous solution of sodium chloride, dried over sodium sulfate and filtered. The solvent was distilled off under reduced pressure, and the residue was purified on a silica gel column to obtain 4.83 g of 2,5-dichloro-3-formylpyridine (yield 62%).

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 8.18 (d, J = 2.4 Hz, 1H), 8.56 (d, J = 2.4 Hz, 1H) 10.38 (s, 1H).

(e) Synthesis of 2,5-dichloro-3-dimethoxymethylpyridine

8.55 g (48.6 mmol) of 2,5-dichloro-3-formylpyridine was dissolved in 60 ml of methanol and heated for 12 hours with 15.47 g (146 mmol) of methyl orthoformate and 0.61 g (2.4 mmol) ) pyridinium p-toluenesulfonate at reflux. After cooling, the volatiles were distilled off under reduced pressure, mixed with 100 ml of water and extracted 3 times with 100 ml of ethyl acetate. The ethyl acetate layers were combined, dried over magnesium sulfate, filtered and the solvent was distilled off under reduced pressure. The residue was purified on a silica gel column to give 9.60 g of 2,5-dichloro-3-dimethoxymethylpyridine (89% yield).

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.40 (s, 6H), 5.52 (s, 1H), 7.94 (d, J = 2.4 Hz, 1H), 8.33 (d, J = 2.4 Hz, 1H).

(f) Synthesis of 2,5-dichloro-3-dimethoxymethyl-4-methylpyridine

5.0 g (22.5 mmol) of 2,5-dichloro-3-dimethoxymethylpyridine was dissolved in 100 ml of anhydrous tetrahydrofuran and cooled to -78 ° C under argon, then 26.3 ml of phenyllithium (0.94 M) was added dropwise. solution in cyclohexane-diethyl ether, 24.7 mmol). The resulting mixture was stirred at -78 ° C for 4 hours to obtain 2,5-dichloro-3-dimethoxymethyl-4-pyridyllithium. Then, 6.39 g (45 mmol) of methyl iodide in 25 ml of tetrahydrofuran was added dropwise and the mixture was stirred at -78 ° C for 1 hour, and then overnight at room temperature. After adding 100 ml of water, the reaction mixture was extracted 3 times with 100 ml of ethyl acetate. The ethyl acetate layers were combined, washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and filtered. The solvent was distilled off and the residue was purified on a silica gel column to obtain 0.51 g of 2,5-dichloro-3-dimethoxymethyl-4-methylpyridine (yield 9.6%).

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.57 (s, 3H), 3.46 (s, 6H), 5.76 (s, 1H), 8.27 ( s, 1H).

(g) Synthesis of 2,5-dichloro-3-formyl-4-methylpyridine

0.51 g (2.16 mmol) of 2,5-dichloro-3-dimethoxymethyl-4-methylpyridine was dissolved in 40 ml of dimethylformamide and mixed with 20 ml of 1 N. hydrochloric acid at room temperature overnight. After adding 40 ml of water, the reaction mixture was neutralized with an aqueous sodium hydroxide solution and extracted 3 times with 50 ml of diethyl ether. The diethyl ether layers were combined, dried over magnesium sulfate and filtered. The solvent was distilled off and the residue was purified on a silica gel column. The purified product was then subjected to deacetalization, as NMR analysis showed the presence of a residue of the starting material. The purified product was dissolved in 1 ml of acetic acid and stirred at room temperature overnight. The progress of the reaction was monitored by HPLC and it turned out that a certain percentage of the starting material remained unreacted. Therefore, the reaction mixture was heated at 50-60 ° C, and then at 70-80 ° C. The reaction mixture was allowed to cool, and after adding 20 ml of water, the reaction mixture was neutralized with an aqueous sodium hydroxide solution and extracted 3 times with 50 ml of diethyl ether. The layers of diethyl ether were combined, washed 3 times with 50 ml of water, dried over magnesium sulfate and filtered. The solvent was distilled off to obtain 0.22 g of 2,5-dichloro-3-formyl-4-methylpyridine.

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.67 (s, 3H), 8.48 (s, 1H), 10.52 (s, 1H).

(h) Synthesis of (2,3,4-trimethoxy-6-methylphenyl) (2,5-dichloro-4-methyl-3-pyridyl) methanol

To 0.30 g (1.16 mmol) of 3,4,5-trimethoxy-2-bromotoluene in tetrahydrofuran (6 ml), cooled to -78 ° C, 0.75 ml of n-butyl lithium was added dropwise in an argon atmosphere ( 1.5 M solution in hexane, 1.13 mmol) and the resulting mixture was stirred at this temperature for 30 minutes to obtain 2,3,4-trimethoxy-6-methylphenyl lithium. Then, 0.22 g (1.16 mmol) of 2,5-dichloro-3-formyl-4-methylpyridine in tetrahydrofuran (2 ml) was added dropwise and the resulting mixture was stirred at -78 ° C for 1 hour. To complete the reaction, 1.5 ml of a saturated aqueous solution of ammonium chloride and 40 ml of water were added sequentially. The reaction mixture was warmed to room temperature and 40 ml of ethyl acetate was extracted 3 times. The ethyl acetate layers were combined, washed with 40 ml of a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and filtered. The solvent was distilled off under reduced pressure, and the residue was purified on a silica gel column to obtain 0.14 g of (2,3,4-trimethoxy-6-methylphenyl) (2,5-dichloro-4-methyl-3-pyridyl) methanol (yield 32 ,4%).

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.18 (s, 3H), 2.50 (s, 3H), 3.59 (s, 3H), 3.81 ( s, 3H) 3.85 (s, 3H), 6.42 (br. 1H), 6.50 (s, 1H), 8.26 (s, 1H).

(i) Synthesis of 3- (2,3,4-trimethoxy-6-methylbenzoyl) -2,5-dichloro-4-methylpyridine (Compound No. 321)

0.14 g (0.38 mmol) (2,3,4-trimethoxy-6-methylphenyl) (2,5-dichloro-4-methyl-3-pyridyl) methanol was dissolved in 5 ml of toluene and heated for 2 hours with 0.67 g (6.8 mmol) of activated manganese dioxide with stirring and boiling under reflux. After the reaction mixture was allowed to cool, it was filtered through celite and the filter cake was washed sufficiently with toluene and then with ethyl acetate. The filtrate and washings were combined and the solvent was removed by distillation under reduced pressure, the residue was purified on a silica gel column to obtain 0.10 g of the desired product.

Mp 77-79 ° C. ¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.37 (s, 3H), 2.53 (s, 3H), 3.30 (s, 3H), 3.76 ( s, 3H), 3.92 (s, 3H), 6.60 (s, 1H), 8.32 (s, 1H).

Production Example 19

Preparation of 3- (2,3,4-trimethoxy-6-methylbenzoyl) -5-chloro-2-methylpyridine (Compound No. 322)

(a) Synthesis of 5-chloro-3-dimethoxymethyl-2-methylpyridine

3.0 g (13.5 mmol) of 2,5-dichloro-3-dimethoxymethylpyridine was dissolved in 30 ml of 1,4-dioxane and heated for 6 hours with 5.6 g (40.5 mmol) of potassium carbonate, 1, 56 g (1.35 mmol) of tetrakistriphenylphosphine palladium and 1.69 g of trimethylboroxine (50% solution in tetrahydrofuran, 6.75 mmol) with stirring and boiling under reflux. Since the presence of unreacted starting material was detected, 0.84 g (3.35 mmol) of trimethylboroxine was added and the reaction mixture was heated with stirring and refluxing for another 6 hours. After the reaction mixture was allowed to cool, it was filtered through celite and a filter cake, washed with 15 ml of ethyl acetate and 15 ml of tetrahydrofuran. The filtrate and washings were combined, the solvent was removed by distillation under reduced pressure, and the residue was purified on a silica gel column to obtain 0.81 g of 5-chloro-3-dimethoxymethyl-2-methylpyridine (30% yield).

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.55 (s, 3H), 3.31 (s, 6H), 5.44 (s, 1H), 7.85 ( d, J = 2.4 Hz, 1H), 8.41 (d, J = 2.4 Hz, 1H).

(b) Synthesis of 5-chloro-3-formyl-2-methylpyridine

0.81 g (4 mmol) of 5-chloro-3-dimethoxymethyl-2-methylpyridine was dissolved in 1.6 ml of acetic acid and stirred at room temperature for 3 hours, and then at 60-70 ° C for 23.5 hours. The reaction mixture was allowed to cool, and after adding 30 ml of water, it was neutralized with an aqueous solution of sodium hydroxide and extracted 3 times with 50 ml of diethyl ether. The diethyl ether layers were combined, washed with water (50 ml), dried over magnesium sulfate and filtered. The solvent was distilled off under reduced pressure, and the residue was purified on a silica gel column to obtain a mixture of the desired product and the starting material, approximately 1: 1. The mixture was dissolved in 5 ml of acetic acid and stirred at 60-70 ° C for 23.5 hours. The reaction mixture was allowed to cool, and then was subjected to treatment and purification as described above to obtain 0.30 g of 5-chloro-3-formyl-2-methylpyridine (48% yield).

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.86 (s, 3H), 8.08 (d, J = 2.4 Hz, 1H), 8.65 (d, J = 2.4 Hz, 1H), 10.30 (s, 1H).

(c) Synthesis of (2,3,4-trimethoxy-6-methylphenyl) (5-chloro-2-methyl-3-pyridyl) methanol

To 0.50 g (1.91 mmol) of 3,4,5-trimethoxy-2-bromotoluene in tetrahydrofuran (10 ml) cooled to -78 ° C, 1.3 ml of n-butyllithium was added dropwise in an argon atmosphere ( 1.5 M solution in hexane, 1.95 mmol) and the resulting mixture was stirred at the same temperature for 30 minutes to obtain 2,3,4-trimethoxy-6-methylphenyl lithium. Then, 0.30 g (1.93 mmol) of 5-chloro-3-formyl-2-methylpyridine in tetrahydrofuran (3 ml) was added dropwise and the resulting mixture was stirred at -78 ° C for 2 hours. To complete the reaction, 26 ml of a saturated aqueous solution of ammonium chloride and 70 ml of water were successively added. The reaction mixture was warmed to room temperature and 70 ml of ethyl acetate was extracted 3 times. The ethyl acetate layers were combined, washed with 70 ml of a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and filtered. The solvent was distilled off under reduced pressure, and the residue was purified on a silica gel column to obtain 0.33 g of (2,3,4-trimethoxy-6-methylphenyl) (5-chloro-2-methyl-3-pyridyl) methanol (yield 51, 4%).

¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.25 (s, 3H), 2.50 (s, 3H), 3.64 (s, 3H), 3.81 ( s, 3H), 3.87 (s, 3H), 5.98 (d, J = 7.6 Hz, 1H), 6.52 (s, 1H), 7.75 (br., 1H), 8 37 (d, J = 2.4 Hz, 1H).

(d) Synthesis of 3- (2,3,4-trimethoxy-6-methylbenzoyl) -5-chloro-2-methylpyridine (Compound No. 322)

0.33 g (0.98 mmol) (2,3,4-trimethoxy-6-methylphenyl) (5-chloro-2-methyl-3-pyridyl) methanol was dissolved in 12 ml of toluene and heated for 2 hours with stirring and refluxing with 1.73 g (17.5 mmol) of activated manganese dioxide. After the reaction mixture was allowed to cool, it was filtered through celite and the filter cake was washed sufficiently with toluene and then with ethyl acetate. The filtrate and washings were combined, distilled off under reduced pressure to remove the solvent, and the residue was purified on a silica gel column to obtain 0.22 g of the desired product (67% yield).

Mp 49-50 ° C. ¹ H-NMR (400 MHz, CDCl ₃ ): δ (ppm) 2.27 (s, 3H), 2.74 (s, 3H), 3.54 (s, 3H), 3.81 ( s, 3H), 3, 92 (s, 3H), 6.58 (s, 1H), 7.61 (d, J = 2.4 Hz, 1H), 8.54 (d, J = 2.4 Hz, 1H).

An example of obtaining an intermediate compound

The following is an example of the preparation of 2,3,4-trimethoxy-6-methylbenzaldehyde, which is used as an intermediate in the above production examples 1, 3, 9, 11 and 16.

Preparation of 2,3,4-trimethoxy-6-methylbenzaldehyde

128 g (0.7 mol) of 3,4,5-trimethoxytoluene dissolved in dry methylene chloride (100 ml) are gradually added dropwise to a solution of 112 g (0.84 mol) of aluminum chloride in dry methylene chloride (500 ml) under ice-cooling. . The mixture was stirred at the same temperature for 45 minutes, a solution of 88.5 g (0.77 mol) of dichloromethyl methyl ether in dry methylene chloride was gradually added dropwise to it over 2 hours. Stirring was continued at the same temperature for 2 hours, and the mixture was gradually brought to room temperature, followed by stirring at room temperature overnight. The reaction mixture was poured into 1 L of ice water, the methylene chloride phase was isolated, and the aqueous phase was extracted twice with 200 ml of methylene chloride. The extract and the methylene chloride phase are combined, washed successively with 200 ml of water, 200 ml of a saturated aqueous solution of sodium bicarbonate, dried over anhydrous magnesium sulfate and the solvent is distilled off under reduced pressure. Embryos for crystallization were introduced into the residue, and the obtained crystals were collected by filtration, washed with hexane and air-dried to obtain 128 g of 2,3,4-trimethoxy-6-methylbenzaldehyde (mp. 55-57 ° C).

Compounds obtained by the methods of Production Examples 1-19 are shown in Tables 1-18 below.

The compounds represented by formulas (I-1) to (I-9) in the tables are the following compounds. In addition, in the tables, Me represents a methyl group, Et represents an ethyl group, Butyl represents a butyl group, ISO-Propyl represents an isopropyl group, Ph represents a phenyl group, Allyl represents an allyl group, c-Hexyl represents a cyclohexyl group, Benzyl represents a benzyl group, Propargyl represents a propargyl group and Pentyl represents a pentyl group.

Table 1 Compounds represented by formula (I-1) No. (X) _n R ¹ (R ² ) _m Physical properties 1 2-Cl, 6-Cl Me 4’-MeO, 5’-MeO so pl. 108-110 ° C 2 2-Cl, 6-Cl Me 4’-MeO, 5’-Me so pl. 123-126 ° C 3 2-Cl, 6-Cl Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 81-83 ° C 4 2-Cl, 6-Cl Me 4’-MeO Colorless oily substance 5 No substitution Me 4'-MeO, 5’-MeO Yellow oily substance 6 No substitution Me 4'-MeO, 5'-Me so pl. 63-65 ° C 7 No substitution Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 59-62 ° C 8 No substitution Me 4’-MeO Pale yellow oily substance nine 2-cl Me 4'-MeO, 5’-MeO so pl. 82-86 ° C 10 2-cl Me 4'-MeO, 5'-Me so pl. 86-89 ° C eleven 2-cl Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 110-112 ° C 12 2-cl Me 4'-Me, 5'-Me, 6'-Me so pl. 88-95 ° C thirteen 2-cl Me 4 ', 5' - (- OCH ₂ O-) so pl. 119-122 ° C 14 2-cl Me 4'-MeO Pale yellow oily substance fifteen 2-cl Et 4'-MeO, 5'-MeO, 6'-MeO 16 2-cl Iso-propyl 4'-MeO, 5'-MeO, 6'-MeO 17 2-cl Me 3'-MeO, 4'-MeO, 5’-MeO, 6'-MeO eighteen 2-cl Me 4'-MeO, 5'-EtO so pl. 89-90 ° C 19 2-cl Me 4'-MeO, 5'-iso-propyl-O- Pale yellow oily substance twenty 2-cl Me 4'-MeO, 5'-Allyl-O- 21 2-cl Me 4'-MeO, 5'-Propargil-O- 22 2-cl Me 4'-MeO, 5'-CF ₃ CH ₂ O- 23 2-cl Me 4'-MeO, 5'-s-Hexyl-O- so pl. 85-86 ° C

table 2 Compounds represented by formula (I-1) No. (X) _n R ¹ (R ² ) _m Physical properties 24 2-cl Me 4'-MeO, 5 '- (CH ₃ ) ₂ N (CH ₂ ) ₂ O- 25 2-cl Me 4'-MeO, 5'-CH ₃ S (CH ₂ ) ₂ O- 26 2-cl Me 4'-MeO, 5'-PhO- Viscous substance 27 2-cl Me 4'-MeO, 5'-benzyl-O- so pl. 116-117 ° C 28 2-cl Me 4'-MeO, 5'-CH ₃ COO- 29th 2-cl Me 4'-MeO, 5'-CH ₃ OSOO- thirty 2-MeO, 6-MeO Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 93-94 ° C 31 2-Cl, 6-MeO Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 85-87 ° C 32 2-MeO Me 4'-MeO, 5'-MeO so pl. 125-127 ° C 33 2-isopropyl-O- Me 4'-MeO, 5'-MeO, 6'-MeO Pale yellow oily substance 34 2-CF ₃ CH ₂ O- Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 80-82 ° C 35 2-CH ₃ O (CH ₂ ) ₂ O- Me 4'-MeO, 5'-MeO, 6'-MeO Pale yellow oily substance 36 2-CH ₃ S (CH ₂ ) ₂ O- Me 4'-MeO, 5'-MeO, 6'-MeO Pale yellow oily substance 37 2-PhO- Me 4'-MeO, 5'-MeO, 6'-MeO Pale yellow oily substance 38 2-benzyl-O- Me 4'-MeO, 5'-MeO, 6'-MeO Pale yellow oily substance 39 2-cyclohexyl-O- Me 4'-MeO, 5'-MeO, 6'-MeO Pale yellow oily substance 40 2-allyl-O- Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 85-86 ° C 41 2-propargyl-O- Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 121-124 ° C 42 2- (CH ₃ ) ₂ N (CH ₂ ) ₂ O- Me 4'-MeO, 5'-MeO, 6'-MeO Pale yellow oily substance 43 2-Cl, 5-Me Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 161-162 ° C 44 2-Cl, 5-allyl Me 4'-MeO, 5'-MeO, 6'-MeO 45 2-Cl, 5-propargyl Me 4'-MeO, 5'-MeO, 6'-MeO 46 2-Cl, 5-CH ₃ O (C = O) - Me 4'-MeO, 5'-MeO, 6'-MeO 47 2-Cl, 5-CH ₃ (C = O) - Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 127-129 ° C

Table 3 Compounds represented by formula (I-1) No. (X) _n R ¹ (R ² ) _m Physical properties 48 2-Cl, 5-Et Me 4'-MeO, 5'-MeO, 6'-MeO 49 2-MeO, 5-Me Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 103-105 ° C fifty 2-mes Me 4'-MeO, 5'-MeO, 6'-MeO Pale yellow oily substance 51 2-Me ₂ N Me 4'-MeO, 5'-MeO, 6'-MeO Pale yellow oily substance 52 2-Cl, 5- (CH ₃ ) ₂ N (C = O) - Me 4'-MeO, 5'-MeO, 6'-MeO 53 2-CN Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 140-144 ° C 54 2-Cl, 5-Cl, 6-Cl Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 114-116 ° C 55 2-Cl, 5-Cl Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 149-151 ° C 56 2-MeO, 5-Cl Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 100-103 ° C 57 2-OH, 5-Cl Me 4'-MeO, 5'-MeO, 6'-MeO 58 2-Cl, 5-Me, 6-Cl Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 101-104 ° C 59 2-Cl, 5-allyl, 6-Cl Me 4'-MeO, 5'-MeO, 6'-MeO Pale yellow oily substance 60 2-Cl, 5-propargyl, 6-Cl Me 4'-MeO, 5'-MeO, 6'-MeO 61 2-Cl, 5-CH ₃ O (C = O) -, 6-Cl Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 107-111 ° C 62 2-Cl, 5-CH ₃ (C = O) -, 6-Cl Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 109-112 ° C 63 2-Cl, 5-Et, 6-Cl Me 4'-MeO, 5'-MeO, 6'-MeO 64 2-Cl, 5- (CH ₃ ) ₂ N (C = O) - Me 4'-MeO, 5'-MeO, 6'-MeO 65 5-me Me 4'-MeO, 5'-MeO, 6'-MeO Pale yellow oily substance 66 5-allyl Me 4'-MeO, 5'-MeO, 6'-MeO 67 5-propargyl Me 4'-MeO, 5'-MeO, 6'-MeO 68 5-CH ₃ O (C = O) - Me 4'-MeO, 5'-MeO, 6'-MeO 69 5-CH ₃ (C = O) - Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 110-113 ° C 70 5-Et Me 4'-MeO, 5'-MeO, 6'-MeO

Table 4 Compounds represented by formula (I-1) No. (X) _n R ¹ (R ² ) _m Physical properties 71 5- (CH ₃ ) ₂ N (C = O) - Me 4'-MeO, 5'-MeO, 6'-MeO 72 2-CH ₃ O (CH ₂ ) ₂ O-, Me 4'-MeO, 5'-MeO so pl. 77-81 ° C 74 2-MeO Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 81-82 ° C 75 2-EtO Me 4'-MeO, 5'-MeO, 6'-MeO Pale yellow oily substance 76 2-mes Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 98-102 ° C 77 2-OH Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 167-173 ° C 78 2-NH ₂ Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 115-118 ° C 79 2-CH ₃ NH Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 150-157 ° C 80 2-CH ₃ COO Me 4'-MeO, 5'-MeO, 6'-MeO Pale yellow oily substance 81 2-isopropyl-O Me 4'-MeO, 5'-MeO, 6'-isopropyl-O- Pale yellow oily substance 82 2-Cl, 6-Cl Et 4'-MeO, 5'-MeO, 6'-MeO so pl. 105-108 ° C 83 2-cl Me 4'-MeO, 5 '- (4-MeO-benzyl) -O- so pl. 123-125 ° C 84 2-me Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 100-103 ° C 85 2-Me, 5-Cl Me 4'-MeO, 5'-MeO, 6'-MeO 86 2-Me, 5-Br Me 4'-MeO, 5'-MeO, 6'-MeO Table 5 Compounds represented by formula (I-2) No. (X) _n R ¹ (R ² ) _m Physical properties 87 2-PhO, 5-Cl Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 147-150 ° C 88 2-OH, 5-Cl Me 4'-MeO, 5'-MeO, 6'-MeO

Table 6 Compounds represented by formula (I-2) No. (X) _n R ¹ (R ² ) _m Physical properties 89 2-Cl, 5-Cl Me 4'-MeO, 5'-MeO so pl. 120-125 ° C 90 2-Cl, 5-Cl Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 106-109 ° C 91 No substitution Me 4'-MeO, 5'-MeO so pl. 98-101 ° C 92 No substitution Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 104-107 ° C 93 2-MeO, 5-Cl Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 130-134 ° C 94 2-MeO 5-Cl Me 4'-MeO, 5'-MeO so pl. 151-156 ° C 95 2-Br, 5-Cl Me 4'-MeO, 5'-MeO, 6'-MeO 96 2-MeS, 5-Cl Me 4'-MeO, 5'-MeO, 6'-MeO 97 2-CN, 5-Cl Me 4'-MeO, 5'-MeO, 6'-MeO 98 2-Cl, 5-Cl, 6-Cl Me 4'-MeO, 5'-MeO so pl. 139-141 ° C 99 2-Cl, 5-Cl, 6-Cl Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 113-115 ° C 100 5-Cl, 6-C1 Me 4'-MeO, 5'-MeO so pl. 94-97 ° C 101 5-cl Me 4'-MeO, 5'-MeO so pl. 90-91 ° C 102 5-cl Me 4'-MeO, 5'-MeO. 6'-MeO so pl. 75-77 ° C 103 5-Cl, 6-C1 Me 4'-MeO, 5'-MeO, 6'-MeO Mp 72-74 ° C 104 5-Cl, 6-MeO Me 4'-MeO, 5'-MeO, 6’-MeO Mp 143-146 ° C 105 5-Cl, 6-MeO Me 4'-MeO, 5'-MeO Mp 112-115 ° C 106 5-Cl, 6-EtO Me 4'-MeO, 5'-MeO, 6'-MeO Mp 82-84 ° C 107 6-MeO Me 4'-MeO, 5'-MeO, 6'-MeO Pale yellow oily substance 108 5-Cl, 6-n-Propyl-O Me 4'-MeO, 5'-MeO, 6'-MeO Pale yellow oily substance 109 6-EtO Me 4'-MeO, 5'-MeO, 6'-MeO Pale yellow oily substance 110 5-Cl, 6-n-Butyl-O Me 4'-MeO, 5'-MeO, 6'-MeO Pale yellow oily substance 111 6-n-Propyl-O Me 4'-MeO, 5'-MeO, 6'-MeO Pale yellow oily substance 112 6-n-Bogil-O Me 4'-MeO, 5'-MeO, 6'-MeO Pale yellow oily substance

Table 7 Compounds represented by formula (I-2) No. (X) _n R ¹ (R ² ) _m Physical properties 113 5-Cl, 6-Propargyl-O Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 131-133 ° C 114 5-Cl, 6-n-Pentyl-O Me 4'-MeO, 5'-MeO, 6'-MeO Pale yellow oily substance 115 5-Cl, 6-OH Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 152-154 ° C 116 6-n-Pentyl-O Me 4'-MeO, 5'-MeO, 6'-MeO Pale yellow oily substance 117 5-Cl, 6-CH ₃ S (CH ₂ ) ₂ O Me 4-MeO, 5'-MeO, 6'-MeO so pl. 62-64 ° C 118 5-Cl, 6-Allyl-O Me 4'-MeO, 5'-MeO, 6'-MeO Pale yellow oily substance 119 5-Cl, 6-CH ₃ O (CH ₂ ) ₂ O Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 78-80 ° C 120 2-MeO, 5-MeO Me 4'-MeO, 5'-MeO, 6'-MeO Toll 135-139 ° C 121 2-MeO Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 97-100 ° C 122 5-MeO Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 103-106 ° C 123 2-Cl, 5-MeO Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 117-119 ° C 124 2-Br, 5-MeO Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 145-147 ° C 125 2-Me, 5-MeO Me 4'-MeO, 5’-MeO, 6'-MeO 126 2-Et, 5-MeO Me 4'-MeO, 5'-MeO, 6'-MeO 127 2-n-Propyl, 5-Meo Me 4’-MeO, 5'-MeO, 6'-MeO 128 2-Allyl, 5-Meo Me 4’-MeO, 5'-MeO, 6'-MeO 129 2-Propargil, 5-Meo Me 4'-MeO, 5'-MeO, 6'-MeO 130 2-EtO, 5-MeO Me 4’-MeO, 5'-MeO, 6’-MeO so pl. 110-112 ° C 131 2-CN, 5-MeO Me 4’-MeO, 5'-MeO, 6'-MeO so pl. 117-120 ° C 132 2-MeS, 5-MeO Me 4'-MeO, 5’-MeO, 6'-MeO so pl. 154-159 ° C 133 5-me Me 4’-MeO, 5’-MeO, 6'-MeO so pl. 98-105 ° C 134 5-br Me 4’-MeO, 5’-MeO, 6'-MeO 135 5-f Me 4'-MeO, 5'-MeO, 6'-MeO

Table 8 Compounds represented by formula (I-3) No. (X) _n R ¹ (R ² ) _m Physical properties 136 6-cl Me 4'-MeO, 5'-MeO, 6’-MeO Yellow oily substance Table 9 Compounds represented by formula (I-4) No. (X) _n R ¹ (R ² ) _m Physical properties 137 No substitution Me 4'-MeO, 5'-MeO, 6’-MeO Table 10 Compounds represented by formula (I-5) No. (X) _n R ¹ (R ² ) _m Physical properties 138 5-Cl, 6-Cl Me 4'-MeO, 5'-MeO, 6'-MeO Mp 109-111 ° C Table 11 Compounds represented by formula (I-6) No. (X) _n R ¹ (R ² ) _m Physical properties 139 4-me Me 4'-MeO, 5'-MeO, 6'-MeO 140 4-Me, 5-Cl Me 4'-MeO, 5'-MeO, 6'-MeO 141 4-Me, 5-Br Me 4'-MeO, 5'-MeO, 6'-MeO

Table 12 No. Formula (X) _n R ¹ (R ² ) _p R ³ Physical properties 142 (I-7) 2-MeO Me 5'-MeO Meo so pl. 90-91 ° C 143 (I-7) 2-Cl, 4-Cl Me 5'-MeO Ph 144 (I-7) 2-Cl, 4-Cl Me 5'-MeO, 6'-MeO Meo 145 (I-7) 2-Cl, 4-MeO Me 5'-MeO, 6'-MeO Meo 146 (I-7) 2-MeO, 4-Cl Me 5'-MeO, 6'-MeO Meo 147 (I-7) 2-F, 4-F Me 5'-MeO, 6'-MeO Meo 148 (I-7) 2-F, 4-MeO Me 5'-MeO, 6'-MeO Meo 149 (I-7) 2-MeO, 4-F Me 5'-MeO, 6'-MeO Meo 150 (I-7) 2-Cl, 4-Cl, 5-Cl Me 5'-MeO, 6'-MeO Meo 151 (I-7) 2-Me, 4-Me Me 5'-MeO, 6'-MeO Meo 152 (I-7) 2-Me, 4-Me, 5-Cl Me 5'-MeO, 6'-MeO Meo 153 (I-7) 2-Me, 4-Me, 5-Br Me 5'-MeO, 6'-MeO Meo 154 (I-7) 2-Me, 4-MeO Me 5'-MeO, 6'-MeO Meo 155 (I-7) 2-Me, 4-MeO, 5-Cl Me 5'-MeO, 6'-MeO Meo 156 (I-7) 2-Me, 4-MeO, 5-Br Me 5'-MeO, 6'-MeO Meo 157 (I-7) 2-MeO, 4-Me Me 5'-MeO, 6'-MeO Meo 158 (I-7) 2-MeO, 4-Me, 5-Cl Me 5'-MeO, 6'-MeO Meo so pl. 84-88 ° C 159 (I-7) 2-MeO, 4-Me, 5-Br Me 5'-MeO, 6'-MeO Meo so pl. 111-114 ° C 160 (I-7) 2-Me, 4-Cl Me 5'-MeO, 6'-MeO Meo 161 (I-7) 2-Me, 4-Cl, 5-Cl Me 5'-MeO, 6'-MeO Meo 162 (I-7) 2-Me, 4-Cl, 5-Br Me 5'-MeO, 6'-MeO Meo 163 (I-7) 2-Cl, 4-Me Me 5'-MeO, 6'-MeO Meo 164 (I-7) 2-Cl, 4-Me, 5-Cl Me 5'-MeO, 6'-MeO Meo 165 (I-7) 2-Cl, 4-Me, 5-Br Me 5'-MeO, 6'-MeO Meo 166 (I-7) 2-CF ₃ , 4-CF ₃ , 5-Cl Me 5'-MeO, 6'-MeO Meo

Table 13 No. Formula (X) _n R ¹ (R ² ) _p R ³ Physical properties 167 (I-7) 2-Cl, 4-CF ₃ , 6-CF ₃ Me 5'-MeO, 6'-MeO Meo so pl. 117-118 ° C 168 (I-7) 2-CF ₃ , 4-CF ₃ , 5-Me Me 5’-MeO, 6'-MeO Meo 169 (I-7) 2-CF ₃ , 4-CF ₃ , 5-Et Me 5'-MeO, 6'-MeO Meo 170 (I-7) 2-CF ₃ , 4-CF ₃ , 5-Alpil Me 5'-MeO, 6'-MeO Meo 171 (I-7) 2-CF ₃ , 4-CF ₃ , 5-n-Propyl Me 5'-MeO, 6'-MeO Meo 172 (I-7) 2-CF ₃ , 4-CF ₃ , 5-Propargyl Me 5'-MeO, 6'-MeO Meo 173 (I-7) 2-CF ₃ , 4-CF ₃ , 5-Me, 6-Cl Me 5'-MeO, 6'-MeO Meo 174 (I-7) 2-CF ₃ , 4-CF ₃ , 5-Et, 6-Cl Me 5'-MeO, 6'-MeO Meo 175 (I-7) 2-CF ₃ , 4-CF ₃ , 5-Allyl, 6-Cl Me 5'-MeO, 6'-MeO Meo 176 (I-7) 2-CF ₃ , 4-CF ₃ , 5-n-Propyl, 6-Cl Me 5'-MeO, 6'-MeO Meo 177 (I-7) 2-CF ₃ , 4-CF ₃ , 5-Propargyl, 6-Cl Me 5'-MeO, 6'-MeO Meo 178 (I-7) 2-CF ₃ , 4-CF ₃ Me 5'-MeO, 6'-MeO Meo 179 (I-7) 2-CF ₃ , 5-CF ₃ , 6-Cl Me 5'-MeO, 6'-MeO Meo 180 (I-7) 2-CF ₃ , 5-CF ₃ Me 5'-MeO, 6'-MeO Meo 181 (I-7) 2-CF ₃ , 4-Me, 5-CF ₃ Me 5'-MeO, 6'-MeO Meo 182 (I-7) 2-CF ₃ , 4-Et, 5-CF ₃ Me 5'-MeO, 6'-MeO Meo 183 (I-7) 2-CF ₃ , 4-Allyl, 5-CF ₃ Me 5'-MeO, 6'-MeO Meo 184 (I-7) 2-CF ₃ , 4-n-propyl, 5-CF ₃ Me 5'-MeO, 6'-MeO Meo 185 (I-7) 2-CF ₃ , 4-Propargyl, 5-CF ₃ Me 5'-MeO, 6'-MeO Meo 186 (I-8) 2-Cl, 3-Cl, 5-Cl Me 5'-MeO, 6'-MeO Meo mp 60-61 ° C 187 (I-8) 2-MeO, 3-Cl, 5-Cl Me 5'-MeO, 6'-MeO Meo mp 128-134 ° C

Table 14 No. Formula (X) _n R ¹ (R ² ) _p R ³ Physical properties 188 (I-8) 2-EtO, 3-Cl, 5-Cl Me 5'-MeO, 6'-MeO Meo Pale yellow oily substance 189 (I-8) 2-MeO, 3-MeO, 5-Cl Me 5'-MeO, 6'-MeO Meo Pale yellow oily substance 190 (I-8) 2-MeO, 3-MeO Me 5'-MeO, 6'-MeO Meo Pale yellow oily substance 191 (I-8) 3-Cl, 5-Cl Me 5’-MeO, 6’-MeO Meo so pl. 109-111 ° C 192 (I-8) 3-cl Me 5'-MeO, 6'-MeO Meo so pl. 90-94 ° C 193 (I-8) 2-Cl, 3-Cl, 5-MeO Me 5'-MeO, 6'-MeO Meo so pl. 98-99 ° C 194 (I-8) 2-Cl, 3-Cl, 5-EtO Me 5'-MeO, 6'-MeO Meo so pl. 110-114 ° C 195 (I-8) 2-Cl, 3-MeO, 5-MeO Me 5'-MeO, 6'-MeO Meo 196 (I-8) 2-Cl, 3-EtO, 5-MeO Me 5'-MeO, 6'-MeO Meo 197 (I-8) 3-MeO Me 5'-MeO, 6'-MeO Meo 198 (I-8) 3-EtO Me 5'-MeO, 6'-MeO Meo 199 (I-8) 2-Cl, 3-MeO, 5-Cl Me 5'-MeO, 6'-MeO Meo tpp 80-86 ° C 200 (I-8) 2-Cl, 3-EtO, 5-Cl Me 5'-MeO, 6'-MeO Meo Pale yellow oily substance 201 (I-8) 3-br Me 5'-MeO, 6'-MeO Meo so pl. 106-107 ° C 202 (I-8) 3-Br, 5-Br Me 5'-MeO, 6'-MeO Meo so pl. 108-110 ° C 203 (I-8) 3-Br, 5-MeO Me 5'-MeO, 6'-MeO Meo Pale yellow oily substance 204 (I-8) 2-F, 3-F, 5-F Me 5'-MeO, 6'-MeO Meo 205 (I-8) 2-MeO, 3-F, 5-F Me 5'-MeO, 6'-MeO Meo 206 (I-8) 2-EtO, 3-F, 5-F Me 5'-MeO, 6'-MeO Meo 207 (I-8) 2-MeO, 3-MeO, 5-F Me 5'-MeO, 6'-MeO Meo 208 (I-8) 3-F, 5-F Me 5'-MeO, 6'-MeO Meo 209 (I-8) 3-f Me 5'-MeO, 6'-MeO Meo 210 (I-8) 3-Me, 5-MeO Me 5'-MeO, 6'-MeO Meo Pale yellow oily substance

Table 15 No. Formula (X) _n R ¹ (R ² ) _p R ³ Physical properties 211 (I-8) 2-Cl, 3-Me, 5-MeO Me 5'-MeO, 6'-MeO Meo Pale yellow oily substance 212 (I-8) 2-Br, 3-Me, 5-MeO Me 5'-MeO, 6'-MeO MeO 213 (I-8) 3-Me, 5-Not Me 5'-MeO, 6'-MeO MeO so pl. 117-122 ° C 214 (I-8) 2-Cl, 3-Me, 5-Me not 5’-MeO, 6'-MeO MeO 215 (I-8) 2-Br, 3-Me, 5-He Me 5'-MeO, 6'-MeO MeO 216 (I-8) 3-Et, 5-MeO Me 5'-MeO, 6'-MeO MeO 217 (I-8) 3-Allyl, 5-MeO Me 5'-MeO, 6'-MeO MeO 218 (I-8) 3-n-Propyl, 5-Meo Me 5'-MeO, 6'-MeO MeO 219 (I-8) 3-Propargyl, 5-MeO Me 5'-MeO, 6'-MeO MeO 220 (I-8) 2-Cl, 3-Et, 5-MeO Me 5'-MeO, 6'-MeO MeO 221 (I-8) 2-Cl, 3-Allyl, 5-MeO Me 5'-MeO, 6'-MeO MeO 222 (I-8) 2-Cl, 3-n-Propyl, 5-MeO Me 5'-MeO, 6'-MeO MeO 223 (I-8) 2-Cl, 3-Propargyl, 5-MeO Me 5'-MeO, 6'-MeO MeO 224 (I-8) 2-Br, 3-Et, 5-MeO Me 5'-MeO, 6'-MeO MeO 225 (I-8) 2-Br, 3-Allyl, 5-MeO Me 5'-MeO, 6'-MeO MeO 226 (I-8) 2-Br, 3-n-Propyl, 5-MeO Me 5'-MeO, 6'-MeO MeO 227 (I-8) 2-Br, 3-Propargal, 5-MeO Me 5'-MeO, 6'-MeO MeO 228 (I-8) 3-Me, 5-Br Me 5'-MeO, 6'-MeO MeO so pl. 88-93 ° C 229 (I-8) 3-Et, 5-Br Me 5'-MeO, 6'-MeO MeO 230 (I-8) 3-Allyl, 5-Br Me 5'-MeO, 6'-MeO MeO 231 (I-8) 3-n-Propyl, 5-Br Me 5'-MeO, 6'-MeO MeO 232 (I-8) 3-Propargil, 5-Br Me 5'-MeO, 6'-MeO MeO 233 (I-8) 3-Me, 5-Br, 6-Cl Me 5'-MeO, 6'-MeO MeO 234 (I-8) 3-Et, 5-Br, 6-Cl Me 5'-MeO, 6'-MeO MeO

Table 16 No. Formula (X) _n R ¹ (R ² ) _p R ³ Physical properties 235 (I-8) 3-Allyl, 5-Br, 6-Cl Me 5'-MeO, 6'-MeO MeO 236 (I-8) 3-n-propnl, 5-Br, 6-Cl Me 5'-MeO, 6'-MeO MeO 237 (I-8) 3-Propargyl, 5-Br, 6-Cl Me 5'-MeO, 6'-MeO MeO 238 (I-8) 3-Me, 5-Br, 6-Br Me 5'-MeO, 6'-MeO MeO 239 (I-8) 3-Et, 5-Br, 6-Br Me 5'-MeO, 6'-MeO MeO 240 (I-8) 3-Allyl, 5-Br, 6-Br Me 5'-MeO, 6'-MeO MeO 241 (I-8) 3-n-Propyl, 5-Br, 6-Br Me 5'-MeO, 6'-MeO MeO 242 (I-8) 3-Propargyl, 5-Br, 6-Br Me 5'-MeO, 6'-MeO MeO 243 (I-8) 3-MeO, 5-MeO Me 5'-MeO, 6'-MeO MeO Red oily substance 244 (I-8) 3-MeO, 5-Cl Me 5'-MeO, 6'-MeO MeO Pale yellow oily substance 245 (I-8) 2-Br, 3-Cl, 5-MeO Me 5'-MeO, 6'-MeO MeO so pl. 97-99 ° C 246 (I-8) 2-Br, 3-Br, 5-Br Me 5'-MeO, 6'-MeO MeO 247 (I-8) 2-Cl, 3-Br, 5-Br Me 5'-MeO, 6'-MeO MeO 248 (I-8) 2-Br, 3-Cl, 5-Cl Me 5'-MeO, 6'-MeO MeO 249 (I-8) 2-Cl, 3-MeO, 5-Cl, 6-Cl Me 5'-MeO, 6'-MeO MeO Pale yellow oily substance 250 (I-8) 2-Br, 3-MeO, 5-Cl, 6-Cl Me 5'-MeO, 6'-MeO MeO Pale yellow oily substance 251 (I-8) 3-EtO, 5-EtO Me 5'-MeO, 6'-MeO MeO so pl. 106-109 ° C 252 (I-8) 3-EtO, 5-Cl Me 5'-MeO, 6'-MeO MeO so pl. 98.5-99.5 ° C 253 (I-8) 2-Br, 3-EtO, 5-Cl Me 5'-MeO, 6'-MeO MeO 254 (I-8) 2-Br, 3-Cl, 5-EtO Me 5'-MeO, 6'-MeO MeO so pl. 113-115 ° C 255 (I-8) 2-Cl, 3-Br, 5-EtO Me 5'-MeO, 6'-MeO MeO 256 (I-8) 2-Br, 3-Br, 5-EtO Me 5'-MeO, 6'-MeO MeO 257 (I-8) 2-Br, 3-Cl, 5-Cl Me 5'-MeO, 6'-MeO meo 258 (I-8) 2-Cl, 3-EtO, 5-Cl, 6-Cl Me 5'-MeO, 6'-MeO MeO

Table 17 No. Formula (X) _n R ¹ (R ² ) _p R ³ Physical properties 259 (I-8) 2-Br, 3-EtO, 5-Cl, 6-Cl Me 5'-Meo, 6'-Meo Meo 260 (I-8) 2-Cl, 3-EtO, 5-Cl, 6-Br Me 5’-MeO, 6'-Meo MeO 261 (I-8) 2-Br, 3-EtO, 5-Cl, 6-Br Me 5'-MeO, 6'-MeO MeO 262 (I-8) 2-F, 3-F, 5-F, 6-F Me 5'-MeO, 6'-MeO MeO so pl. 85-87 ° C 263 (I-8) 2-Br, 3-F, 5-F Me 5'-MeO, 6'-MeO MeO 264 (I-8) 2-F, 3-Me, 5-F Me 5'-MeO, 6'-MeO MeO 265 (I-8) 2-Br, 3-F, 5-F, 6-Br Me 5'-MeO, 6'-MeO MeO 266 (I-8) 2-Cl, 3-F, 5-F Me 5'-MeO, 6'-MeO MeO 267 (I-8) 2-Br, 3-Br, 5-Br, 6-Br Me 5'-MeO, 6'-MeO MeO 268 (I-8) 2-Cl, 3-Cl, 5-Cl, 6-Cl Me 5'-MeO, 6'-MeO MeO 269 (I-8) 3-Br, 5-F Me 5'-MeO, 6'-MeO MeO 270 (I-8) 2-Br, 3-F, 5-F, 6-F Me 5'-MeO, 6'-MeO MeO 271 (I-8) 3-F, 5-CH ₃ Me 5'-MeO, 6'-MeO MeO 272 (I-8) 3-Cl, 5-CH ₃ Me 5'-MeO, 6'-MeO MeO tpp 84-88 ° C 273 (I-8) 3-F, 5-MeO Me 5'-MeO, 6'-MeO MeO 274 (I-8) 2-Cl, 3-CF ₃ , 6-CF ₃ Me 5'-MeO, 6'-MeO MeO so pl. 85-88 ° C 275 (I-8) 3-CF ₃ , 6-CF ₃ Me 5'-MeO, 6'-MeO MeO 276 (I-8) 3-CF ₃ , 5-Me, 6-CF ₃ Me 5'-MeO, 6'-MeO MeO 277 (I-8) 3-CF ₃ , 5-ЕF ₃ , 6-СF ₃ Me 5'-MeO, 6'-MeO MeO 278 (I-8) 3-CF ₃ , 5-Allyl, 6-CF ₃ Me 5'-MeO, 6'-MeO MeO 279 (I-8) 3-CF ₃ , 5-n-Propyl, 6-CF ₃ Me 5'-MeO, 6'-MeO MeO 280 (I-8) 3-CF ₃ , 5-Propargil, 6-CF ₃ Me 5'-MeO, 6'-MeO MeO 281 (I-8) 2-Cl, 3-CF ₃ , 5-CF ₃ , 6-Cl Me 5'-MeO, 6'-MeO MeO 282 (I-8) 2-Cl, 3-CF ₃ , 5-CF ₃ Me 5'-MeO, 6'-MeO MeO

Table 18 No. Formula (X) _n R ¹ (R ² ) _p R ³ Physical properties 283 (I-8) 3-CF ₃ , 5-CF ₃ Me 5'-MeO, 6'-MeO MeO 284 (I-9) 3-Cl, 5-Cl, 6-Cl Me 5'-MeO, 6'-MeO MeO so pl. 144-147 ° C 285 (I-9) 3-F, 5-F, 6-F Me 5'-MeO, 6'-MeO MeO 286 (I-9) 3-Br, 5-Br Me 5'-MeO, 6'-MeO MeO Pale yellow oily substance 287 (I-1) 2-MeO Me 5'-cyclohexyl-O MeO mp 97-100 ° C 288 (I-8) 2-Me, 3-Cl, 6-Cl Me 5'-MeO MeO so pl. 111-113 ° C 289 (I-8) 2-Me, 3-Cl, 6-Cl Et 5'-MeO MeO so pl. 88-94 ° C 290 (I-8) 2-Me, 3-Cl Me 5'-MeO MeO so pl. 117-118 ° C 291 (I-8) 2-Cl, 3-Br, 5-MeO Me 5'-MeO, 6'-MeO MeO Brown oily substance 292 (I-8) 2-Br, 3-Br, 5-MeO Me 5'-MeO, 6'-MeO MeO Yellow oily substance 293 (I-7) 2-MeO, 4-Br, 5-Cl Me 5'-MeO, 6'-MeO MeO so pl. 92-94 ° C 294 (I-7) 2-MeO, 4-Et, 5-Cl Me 5'-MeO, 6'-MeO MeO Yellow oily substance 295 (I-7) 2-MeO, 4-Cl, 5-Cl Me 5'-MeO MeO so pl. 139-141 ° C 296 (I-7) 2-MeO, 4-Cl, 5-Cl Me 5'-EtO MeO so pl. 110-112 ° C 297 (I-7) 2-EtO, 4-Br, 5-Cl Me 5'-MeO, 6'-MeO MeO Yellow oily substance 298 (I-7) 2-EtO, 4-Me, 5-Cl Me 5'-MeO, 6'-MeO MeO Yellow oily substance 299 (I-7) 2-EtO, 4-Cl, 5-Br Me 5'-MeO, 6'-MeO MeO Pale yellow oily substance 300 (I-7) 2-MeO, 4-Cl, 5-I Me 5'-MeO, 6'-MeO MeO Colorless oily substance 301 (I-7) 2-MeO, 4-MeO, 5-I Me 5'-MeO, 6'-MeO MeO Colorless oily substance 302 (I-7) 2-MeO, 4-MeS, 5-Cl Me 5'-MeO, 6'-MeO MeO so pl. 98-104 ° C 303 (I-7) 2-MeO, 4-MeO, 5-Cl Me 5'-MeO, 6'-MeO MeO so pl. 93-94 ° C 304 (I-7) 2-MeO, 4-Br, 5-Br Me 5'-MeO, 6'-MeO MeO so pl. 149-150 ° C 305 (I-7) 2-MeO, 4-Br, 5-Me Me 5'-MeO, 6'-MeO MeO so pl. 140-142 ° C 306 (I-7) 2-MeO, 4-CF ₃ , 5-Br Me 5'-MeO, 6'-MeO MeO so pl. 128-129 ° C 307 (I-7) 2-MeO, 4-Cl, 5-Cl Me 5'-MeO, 6'-MeO MeO so pl. 84-86 ° C

Table 18 (continued) No. Formula (X) _n R ¹ (R ² ) _p R ³ Physical properties 308 (I-7) 2-Cl, 4-Cl, 5-Me Me 5'-MeO, 6'-MeO Meo so pl. 78-80 ° C 309 (I-7) 2-Cl, 4-Cl, 5-I Me 5'-MeO, 6'-MeO Meo Oily substance 310 (I-7) 2-F, 4-I, 5-Me Me 5'-MeO, 6'-MeO Meo so pl. 140-141 ° C 311 (I-7) 2-F, 4-Me, 5-Me Me 5'-MeO, 6'-MeO Meo so pl. 91-92 ° C 312 (I-7) 2-MeO, 4-Me, 5-Me Me 5'-MeO, 6'-MeO Meo so pl. 84-86 ° C 313 (I-7) 2-EtO, 4-Me, 5-Me Me 5'-MeO, 6'-MeO Meo so pl. 74-75 ° C 314 (I-7) 2-MeS, 4-Me, 5-Me Me 5'-MeO, 6'-MeO Meo Oily substance 315 (I-7) 2-MeO, 4-Cl, 5-Br Me 5'-MeO, 6'-MeO Meo so pl. 84-87 ° C 316 (I-7) 2-MeO, 4-Cl, 5-Me Me 5'-MeO, 6'-MeO Meo so pl. 88-90 ° C 317 (I-7) 2-MeO, 4-ethynyl, 5-Cl Me 5'-MeO, 6'-MeO Meo so pl. 113-115 ° C 318 (I-7) 2-MeO, 4-CH ₂ F, 5-Cl Me 5'-MeO, 6'-MeO Meo so pl. 82-84 ° C 319 (I-7) 2-MeO, 4-Me, 5-Cl Me 5'-MeO Meo so pl. 129-130 ° C 320 (I-7) 2-Cl, 4-Me, 6-Cl Me 5'-MeO, 6'-MeO Meo Pale yellow oily substance 321 (I-7) 2-Cl, 4-Me, 5-Cl Me 5'-MeO, 6'-MeO Meo so pl. 77-79 ° C 322 (I-7) 2-Me, 5-Cl Me 5'-MeO, 6'-MeO Meo so pl. 49-50 ° C

Compounds represented by formula (X), which are used as intermediates, prepared according to the methods of Preparation 1, 3, 5, 6, 8, 9, 11 and 16, are shown in the following Tables 19-36.

The compounds represented by the general formulas (X-1) to (X-9) in the tables are the following compounds.

In addition, in these tables Me represents a methyl group, Et represents an ethyl group, Butyl represents a butyl group, ISO-Propyl represents an isopropyl group, Ph represents a phenyl group, Allyl represents an allyl group, c-Hexyl represents a cyclohexyl group, Benzyl represents a benzyl group, Propargyl represents a propargyl group and Pentyl represents a pentyl group.

Table 19 Compounds represented by formula (X-1) No. (X) _n R ¹ (R ² ) _m Physical properties 1 2-Cl, 6-Cl Me 4'-MeO, 5'-MeO Viscous substance 2 2-Cl, 6-Cl Me 4'-MeO, 5'-Me Viscous substance 3 2-Cl, 6-Cl Me 4'-MeO, 5'-MeO, 6'-MeO Viscous substance 4 2-Cl, 6-Cl Me 4'-MeO Viscous substance 5 No substitution Me 4'-MeO, 5'-MeO 6 No substitution Me 4'-MeO, 5'-Me 7 No substitution Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 132-135 ° C 8 No substitution Me 4’-MeO nine 2-cl Me 4'-MeO, 5'-MeO 10 2-cl Me 4'-MeO, 5'-Me eleven 2-cl Me 4’-MeO, 5’-MeO, 6'-MeO Viscous substance 12 2-cl Me 4'-Me, 5'-Me, 6'-Me so pl. 125-127 ° C thirteen 2-cl Me 4 ', 5' - (- OCH ₂ O-) so pl. 127-130 ° C 14 2-cl Me 4'-MeO fifteen 2-cl Et 4'-MeO, 5'-MeO, 6'-MeO 16 2-cl iso-propyl 4'-MeO, 5'-MeO, 6'-MeO 17 2-cl Me 3'-MeO, 4'-MeO, 5’-MeO, 6'-MeO eighteen 2-cl Me 4'-MeO, 5'-EtO Viscous substance 19 2-cl Me 4'-MeO, 5'-ISO-Propyl-O Viscous substance twenty 2-cl Me 4'-MeO, 5'-Allyl-O 21 2-cl Me 4'-MeO, 5'-Propargil-O 22 2-cl Me 4'-MeO, 5'-CF ₃ CH ₂ O- 23 2-cl Me 4'-MeO, 5'-s-Hexyl-O Viscous substance

Table 20 Compounds represented by formula (X-1) No. (X) _n R ¹ (R ² ) _m Physical properties 24 2-cl Me 4'-MeO, 5 '- (CH ₃ ) ₂ N (CH ₂ ) ₂ O- 25 2-cl Me 4'-MeO, 5'-CH ₃ S (CH ₂ ) ₂ O- 26 2-cl Me 4'-MeO, 5'-PhO- 27 2-cl Me 4'-MeO, 5'-Benzyl-O- Viscous substance 28 2-cl Me 4'-MeO, 5'-CH ₃ COO- 29th 2-cl Me 4'-MeO, 5'-CH ₃ OSOO- thirty 2-MeO, 6-MeO Me 4'-MeO, 5'-MeO, 6’-MeO 31 2-Cl, 6-MeO Me 4’-MeO, 5'-MeO, 6’-MeO 32 2-MeO Me 4'-MeO, 5'-MeO 33 2-Iso-Propyl-O Me 4'-MeO, 5'-MeO, 6'-MeO 34 2-CF ₃ CH ₂ O- Me 4'-MeO, 5'-MeO, 6’-MeO 35 2-CH ₃ O (CH ₂ ) ₂ O- Me 4'-MeO, 5'-MeO, 6'-MeO 36 2-CH ₃ S (CH ₂ ) ₂ O- Me 4'-MeO, 5'-MeO, 6’-MeO 37 2-PhO- Me 4’-MeO, 5'-MeO, 6’-MeO 38 2-Benzyl-O- Me 4'-MeO, 5'-MeO, 6’-MeO 39 2-s-hexyl-o- Me 4’-MeO, 5'-MeO, 6’-MeO 40 2-Allyl-O- Me 4’-MeO, 5'-MeO, 6'-MeO 41 2-Propargyl-O- Me 4'-MeO, 5'-MeO, 6'-MeO 42 2- (CH ₃ ) ₂ N (CH ₂ ) ₂ O- Me 4’-MeO, 5'-MeO, 6’-MeO 43 2-Cl, 5-Not Me 4’-MeO, 5'-MeO, 6'-MeO 44 2-Cl, 5-Allyl Me 4'-MeO, 5'-MeO, 6'-MeO 45 2-Cl, 5-prolartle Me 4’-MeO, 5'-MeO, 6’-MeO 46 2-Cl, 5-CH ₃ O (C = O) - Me 4’-MeO, 5'-MeO, 6'-MeO 47 2-Cl, 5-CH ₃ (C = O) - Me 4’-MeO, 5'-MeO, 6’-MeO

Table 21 Compounds represented by formula (X-1) No. (X) _n R ¹ (R ² ) _m Physical properties 48 2-Cl, 5-Et Me 4'-MeO, 5’-MeO, 6'-MeO 49 2-MeO, 5-Me Me 4'-MeO, 5’-MeO, 6’-MeO fifty 2-mes Me 4'-MeO, 5'-MeO, 6'-MeO 51 2-Me ₂ N Me 4'-MeO, 5-MeO, 6’-MeO 52 2-Cl, 5- (CH ₃ ) ₂ N (C = O) - Me 4'-MeO, 5'-MeO, 6’-MeO 53 2-CN Me 4'-MeO, 5’-MeO, 6'-MeO 54 2-Cl, 5-Cl, 6-Cl Me 4'-MeO, 5'-MeO, 6’-MeO Viscous substance 55 2-Cl, 5-Cl Me 4’-MeO, 5'-MeO, 6’-MeO 56 2-MeO, 5-Cl Me 4’-MeO, 5’-MeO, 6'-MeO 57 2-OH, 5-Cl Me 4'-MeO, 5’-MeO, 6’-MeO 58 2-Cl, 5-Me, 6-Cl Me 4'-MeO, 5’-MeO, 6’-MeO Viscous substance 59 2-Cl, 5-Allyl, 6-Cl Me 4'-MeO, 5'-MeO, 6'-MeO Viscous substance 60 2-Cl, 5-Propargyl, 6-Cl Me 4'-MeO, 5'-MeO, 6’-MeO 61 2-Cl, 5-CH ₃ O (C = O) -, 6-Cl Me 4'-MeO, 5’-MeO, 6’-MeO so pl. 133-135 ° C 62 2-Cl, 5-CH ₃ CH (OH) -, 6-Cl Me 4’-MeO, 5'-MeO, 6'-MeO so pl. 141-158 ° C 63 2-Cl, 5-Et, 6-Cl Me 4'-MeO, 5’-MeO, 6'-MeO 64 2-Cl, 5- (CH ₃ ) ₂ N (C = O) - Me 4'-MeO, 5-MeO, 6’-MeO 65 5-me Me 4'-MeO, 5’-MeO, 6’-MeO 66 5-allyl Me 4'-MeO, 5’-MeO, 6’-MeO 67 5-Propargil Me 4'-MeO, 5’-MeO, 6'-MeO 68 5-CH ₃ O (C = O) - Me 4'-MeO, 5’-MeO, 6'-MeO 69 5-CH ₃ (C = O) - Me 4'-MeO, 5’-MeO, 6'-MeO 70 5-Et Me 4'-MeO, 5’-MeO, 6’-MeO

Table 22 Compounds represented by formula (X-1) No. (X) _n R ¹ (R ² ) _m Physical properties 71 5- (CH ₃ ) ₂ N (C = O) - Me 4'-MeO, 5'-MeO, 6’-MeO 72 2-CH ₃ O (CH ₂ ) ₂ O- Me 4'-MeO, 5'-MeO 73 2- (6'-phenyl) -O- Me 4’-MeO, 5’-MeO, 6’-O- (2-Pyridyl) 74 2-MeO Me 4'-MeO, 5'-MeO, 6’-MeO 75 2-EtO Me 4'-MeO, 5'-MeO, 6'-MeO 76 2-mes Me 4'-MeO, 5'-MeO, 6'-OH 77 2-OH Me 4'-MeO, 5'-MeO, 6'-MeO 78 2-NH ₂ Me 4'-MeO, 5'-MeO, 6'-MeO 79 2-CH ₃ NH Me 4'-MeO, 5'-MeO, 6'-MeO 80 2-CH ₃ COO Me 4'-MeO, 5'-MeO, 6'-MeO 81 2-iso-propyl-o- Me 4'-MeO, 5'-MeO, 6'-iso-Propyl-O- 82 2-Cl, 6-Cl Et 4'-MeO, 5'-MeO, 6’-MeO 83 2-cl Me 4'-MeO, 5 '- (4-MeO-Benzyl) O Viscous substance 84 2-me Me 4'-MeO, 5'-MeO, 6’-MeO 85 2-Me, 5-Cl Me 4'-MeO, 5'-MeO, 6’-MeO 86 2-Me, 5-Br Me 4'-MeO, 5'-MeO, 6'-MeO Table 23 Compounds represented by formula (X-2) No. (X) _p R ¹ (R ² ) _m Physical properties 87 2-PhO, 5-Cl Me 4'-MeO, 5'-MeO, 6'-MeO 88 2-OH, 5-Cl Me 4'-MeO, 5'-MeO, 6’-MeO

Table 24 Compounds represented by formula (X-2) No. (X) _n R ¹ (R ² ) _m Physical properties 89 2-Cl, 5-Cl Not 4'-MeO, 5'-MeO so pl. 134-136 ° C 90 2-Cl, 5-Cl Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 162-165 ° C 91 No substitution Me 4'-MeO, 5'-MeO 92 No substitution Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 101-106 ° C 93 2-MeO, 5-Cl Me 4'-MeO, 5'-MeO, 6'-MeO 94 2-MeO, 5-Cl Me 4'-MeO, 5'-MeO 95 2-Br, 5-Cl Me 4'-MeO, 5'-MeO, 6'-MeO 96 2-MeS, 5-Cl Me 4'-MeO, 5'-MeO, 6'-MeO 97 2-CN, 5-Cl Me 4'-MeO, 5'-MeO, 6'-MeO 98 2-Cl, 5-Cl, 6-Cl Me 4'-MeO, 5'-MeO so pl. 156-158 ° C 99 2-Cl, 5-Cl, 6-Cl Me 4'-MeO, 5'-MeO, 6’-MeO so pl. 131-135 ° C 100 5-Cl, 6-Cl Me 4'-MeO, 5'-MeO Viscous substance 101 5-cl Me 4'-MeO, 5'-MeO 102 5-cl Me 4'-MeO, 5'-MeO, 6'-MeO so pl. 102-105 ° C 103 5-Cl, 6-Cl Me 4'-MeO, 5'-MeO, 6'-MeO tpp 95-98 ° C 104 5-Cl, 6-MeO Me 4'-MeO, 5'-MeO, 6'-MeO 105 5-Cl, 6-MeO Me 4'-MeO, 5'-MeO 106 5-Cl, 6-EtO Me 4'-MeO, 5'-MeO, 6'-MeO 107 6-MeO Me 4'-MeO, 5'-MeO, 6'-MeO 108 5-Cl, 6-n-Propyl-O Me 4'-MeO, 5'-MeO, 6'-MeO 109 6-EtO Me 4'-MeO, 5'-MeO, 6'-MeO 110 5-Cl, 6-n-Butyl-O Me 4'-MeO, 5'-MeO, 6'-MeO 111 6-n-Propyl-O Me 4'-MeO, 5'-MeO, 6'-MeO 112 6-n-Butyl-O Me 4'-MeO, 5'-MeO, 6'-MeO

Table 25 Compounds represented by formula (X-2) No. (X) _n R ¹ (R ² ) _m Physical properties 113 5-Cl, 6-Propargyl-O Me 4'-MeO, 5'-MeO, 6'-MeO 114 5-Cl, 6-n-Pentyl-O Me 4'-MeO, 5'-MeO, 6'-MeO 115 5-Cl, 6-OH Me 4'-MeO, 5'-MeO, 6'-MeO 116 6-n-Pentyl-O Me 4'-MeO, 5'-MeO, 6'-MeO 117 5-Cl, 6-CH ₃ S (CH ₂ ) ₂ O Me 4'-MeO, 5'-MeO, 6'-MeO 118 5-Cl, 6-Allyl-O Me 4’-MeO, 5'-MeO, 6'-MeO 119 5-Cl, 6-CH ₃ O (CH ₂ ) ₂ O Me 4'-MeO, 5'-MeO, 6'-MeO 120 2-MeO, 5-MeO Me 4’-MeO, 5'-MeO, 6'-MeO 121 2-MeO Me 4'-MeO, 5'-MeO, 6'-MeO 122 5-MeO Me 4'-MeO, 5'-MeO, 6'-MeO 123 2-Cl, 5-MeO Me 4'-MeO, 5'-MeO, 6'-MeO 124 2-Br, 5-MeO Me 4'-MeO, 5'-MeO, 6'-MeO 125 2-Me, 5-MeO Me 4'-MeO, 5'-MeO, 6'-MeO 126 2-Et, 5-MeO He 4'-MeO, 5'-MeO, 6'-MeO 127 2-n-Propyl, S-MeO Me 4’-MeO, 5'-MeO, 6'-MeO 128 2-Allkl, 5-MeO Me 4'-MeO, 5'-MeO, 6'-MeO 129 2-Propargil, 5-Meo Me 4'-MeO, 5’-MeO, 6'-MeO 130 2-EtO, 5-MeO Me 4’-MeO, 5'-MeO, 6'-MeO 131 2-CN, 5-MeO Me 4'-MeO, 5’-MeO, 6'-MeO 132 2-MeS, 5-MeO Me 4'-MeO, 5'-MeO, 6'-MeO 133 5-me Me 4'-MeO, 5'-MeO, 6'-MeO 134 5-br Me 4'-MeO, 5'-MeO, 6’-MeO 135 5-f Me 4'-MeO, 5’-MeO, 6'-MeO

Table 26 Compounds represented by formula (X-3) No. (X) _n R ¹ (R ² ) _m Physical properties 136 6-cl Me 4'-MeO, 5’-MeO, 6'-MeO Viscous substance Table 27 Compounds represented by formula (X-4) No. (X) _n R ¹ (R ² ) _m Physical properties 137 No substitution Me 4'-MeO, 5'-MeO, 6'-MeO Table 28 Compounds represented by formula (X-5) No. (X) _n R ¹ (R ² ) _m Physical properties 138 5-Cl, 6-Cl Me 4’-MeO, 5'-MeO, 6’-MeO tpp 71-73 ° C Table 29 Compounds represented by formula (X-6) No. (X) _n R ¹ (R ² ) _m Physical properties 139 4-me Me 4'-MeO, 5'-MeO, 6'-Meo 140 4-Me, 5-Cl Me 4'-MeO, 5'-MeO, 6'-MeO 141 4-Me, 5-Br Me 4'-MeO, 5'-MeO, 6'-MeO

Table 30 No. Formula (X) _n R ¹ (R ² ) _p R ³ Physical properties 142 (X-7) 2-MeO Me 5'-MeO Meo Viscous substance 143 (X-7) 2-Cl, 4-Cl Me 5'-MeO Pho 144 (X-7) 2-Cl, 4-Cl Me 5'-MeO, 6'-MeO Meo 145 (X-7) 2-Cl, 4-MeO Me 5'-MeO, 6'-MeO Meo 146 (X-7) 2-MeO, 4-Cl Me 5'-MeO, 6'-MeO Meo 147 (X-7) 2-F, 4-F Me 5'-MeO, 6'-MeO Meo 148 (X-7) 2-F, 4-MeO Me 5'-MeO, 6'-MeO Meo 149 (X-7) 2-MeO, 4-F Me 5'-MeO, 6'-MeO Meo 150 (X-7) 2-Cl, 4-Cl, 5-Cl Me 5'-MeO, 6'-MeO Meo 151 (X-7) 2-Me, 4-Me Me 5'-MeO, 6'-MeO Meo 152 (X-7) 2-Me, 4-Me, 5-Cl Me 5'-MeO, 6'-MeO Meo 153 (X-7) 2-Me, 4-Me, 5-Br Me 5'-MeO, 6'-MeO Meo 154 (X-7) 2-Me, 4-MeO Me 5'-MeO, 6'-MeO Meo 155 (X-7) 2-Me, 4-MeO, 5-Cl Me 5'-MeO, 6'-MeO Meo 156 (X-7) 2-Me, 4-MeO, 5-Br Me 5'-MeO, 6'-MeO Meo 157 (X-7) 2-MeO, 4-Me Me 5'-MeO, 6'-MeO Meo 158 (X-7) 2-MeO, 4-Me, 5-Cl Me 5'-MeO, 6'-MeO Meo Viscous substance 159 (X-7) 2-MeO, 4-Me, 5-Br Me 5'-MeO, 6'-MeO Meo Viscous substance 160 (X-7) 2-Me, 4-Cl Me 5'-MeO, 6'-MeO Meo 161 (X-7) 2-Me, 4-Cl, 5-Cl Me 5'-MeO, 6'-MeO Meo 162 (X-7) 2-Me, 4-Cl, 5-Br Me 5'-MeO, 6'-MeO Meo 163 (X-7) 2-Cl, 4-Me Me 5'-MeO, 6'-MeO Meo 164 (X-7) 2-Cl, 4-Me, 5-Cl Me 5'-MeO, 6'-MeO Meo 165 (X-7) 2-Cl, 4-Me, 5-Br Me 5'-MeO, 6'-MeO Meo 166 (X-7) 2-CF ₃ , 4-CF ₃ , 6-Cl Me 5'-MeO, 6'-MeO Meo

Table 31 No. Formula (X) _n R ¹ (R ² ) _p R ³ Physical properties 167 (X-7) 2-Cl, 4-CF ₃ , 6-CF ₃ Me 5'-MeO, 6'-MeO Meo Viscous substance 168 (X-7) 2-CF ₃ , 4-CF ₃ , 5-Me Me 5'-MeO, 6'-MeO Meo 169 (X-7) 2-CF ₃ , 4-CF ₃ , 5-Et Me 5'-MeO, 6'-MeO Meo 170 (X-7) 2-CF ₃ , 4-CF ₃ , 5-Allyl Me 5'-MeO, 6'-MeO Meo 171 (X-7) 2-CF ₃ , 4-CF ₃ , 5-n-Propyl Me 5'-MeO, 6'-MeO Meo 172 (X-7) 2-CF ₃ , 4 – CF ₃ , 5-Propargyl Me 5'-MeO, 6'-MeO Meo 173 (X-7) 2-CF ₃ , 4-CF ₃ , 5-Me, 6-C1 Me 5'-MeO, 6'-MeO Meo 174 (X-7) 2-CF ₃ , 4-CF ₃ , 5-Et, 6-Cl Me 5'-MeO, 6'-MeO Meo 175 (X-7) 2-CF ₃ , 4-CF ₃ , 5-Allyl, 6-Cl Me 5'-MeO, 6'-MeO Meo 176 (X-7) 2-CF ₃ , 4-CF ₃ , 5-n-Propyl, 6-Cl Me 5’-MeO, 6'-MeO Meo 177 (X-7) 2-CF ₃ , 4-CF ₃ , 5-Propargyl, 6-Cl Me 5'-MeO, 6'-MeO Meo 178 (X-7) 2-CF ₃ , 4-CF ₃ Me 5'-MeO, 6'-MeO Meo 179 (X-7) 2-CF ₃ , 5-CF ₃ , 6-Cl Me 5'-MeO, 6'-MeO Meo 180 (X-7) 2-CF ₃ , 5-CF ₃ Me 5'-MeO, 6'-MeO Meo 181 (X-7) 2-CF ₃ , 4-Me, 5-CF ₃ Me 5'-MeO, 6'-MeO Meo 182 (X-7) 2-CF ₃ , 4-Et, 5-CF ₃ Me 5'-MeO, 6'-MeO Meo 183 (X-7) 2-CF ₃ , 4-Allyl, 5-CF ₃ Me 5'-MeO, 6'-MeO Meo 184 (X-7) 2-CF ₃ , 4-n-Propyl, 5-CF ₃ Me 5'-MeO, 6'-MeO Meo 185 (X-7) 2-CF ₃ , 4-Propargyl, 5-CF ₃ Me 5'-MeO, 6'-MeO Meo 186 (X-8) 2-Cl, 3-Cl, 5-Cl Me 5'-MeO, 6'-MeO Meo Non-crystalline 187 (X-8) 2-MeO, 3-Cl, 5-Cl Me 5'-MeO, 6'-MeO Meo

Table 32 No. Formula (X) _n R ¹ (R ² ) _p R ³ Physical properties 188 (X-8) 2-EtO, 3-Cl, 5-Cl Me 5'-MeO, 6'-MeO MeO 189 (X-8) 2-MeO, 3-MeO, 5-Cl Me 5'-MeO, 6'-MeO MeO 190 (X-8) 2-MeO, 3-MeO Me 5'-MeO, 6'-MeO MeO 191 (X-8) 3-Cl, 5-Cl Me 5'-MeO, 6'-MeO MeO so pl. 136-140 ° C 192 (X-8) 3-cl Me 5'-MeO, 6'-MeO MeO so pl. 160-162 ° C 193 (X-8) 2-Cl, 3-Cl, 5-MeO Me 5'-MeO, 6'-MeO MeO 194 (X-8) 2-Cl, 3-Cl, 5-EtO Me 5'-MeO, 6'-MeO MeO 195 (X-8) 2-Cl, 3-MeO, 5-MeO Me 5'-MeO, 6'-MeO MeO 196 (X-8) 2-Cl, 3-EtO, 5-MeO Me 5'-MeO, 6'-MeO MeO 197 (X-8) 3-MeO Me 5'-MeO, 6'-MeO MeO 198 (X-8) 3-EtO Me 5'-MeO, 6'-MeO MeO 199 (X-8) 2-Cl, 3-MeO, 5-Cl Me 5'-MeO, 6'-MeO MeO 200 (X-8) 2-Cl, 3-EtO, 5-Cl Me 5'-MeO, 6'-MeO MeO 201 (X-8) 3-br Me 5'-MeO, 6'-MeO MeO so pl. 168-169 ° C 202 (X-8) 3-Br, 5-Br Me 5'-MeO, 6'-MeO MeO Viscous substance 203 (X-8) 3-Br, 5-MeO Me 5'-MeO, 6'-MeO MeO so pl. 90-93 ° C 204 (X-8) 2-F, 3-F, 5-F Me 5'-MeO, 6'-MeO MeO 205 (X-8) 2-MeO, 3-F, 5-F Me 5'-MeO, 6'-MeO MeO 206 (X-8) 2-EtO, 3-F, 5-F Me 5'-MeO, 6'-MeO MeO 207 (X-8) 2-MeO, 3-MeO, 5-F Me 5'-MeO, 6'-MeO MeO 208 (X-8) 3-F, 5-F Me 5'-MeO, 6'-MeO MeO 209 (X-8) 3-f Me 5’-MeO, 6'-MeO MeO 210 (X-8) 3-Me, 5-MeO Me 5'-MeO, 6'-MeO MeO

Table 33 No. Formula (X) _n R ¹ (R ² ) _p R ³ Physical
properties 211 (X-8) 2-Cl, 3-Me, 5-MeO Me 5'-MeO, 6'-MeO Meo 212 (X-8) 2-Br, 3-Me, 5-MeO Me 5'-MeO, 6'-MeO Meo 213 (X-8) 3-Me, 5-Me Me 5'-MeO, 6'-MeO Meo 214 (X-8) 2-Cl, 3-Me, 5-Me Me 5'-MeO, 6'-MeO Meo 215 (X-8) 2-Br, 3-Me, 5-Me Me 5'-MeO, 6'-MeO Meo 216 (X-8) 3-Et, 5-MeO Me 5'-MeO, 6'-MeO Meo 217 (X-8) 3-Allyl, 5-MeO Me 5'-MeO, 6'-MeO Meo 218 (X-8) 3-n-Propyl, 5-MeO Me 5'-MeO, 6'-MeO Meo 219 (X-8) 3-Propargyl, 5-MeO Me 5'-MeO, 6'-MeO Meo 220 (X-8) 3-Cl, 3-Et, 5-MeO Me 5'-MeO, 6'-MeO Meo 221 (X-8) 2-Cl, 3-Allyl, 5-MeO Me 5'-MeO, 6'-MeO Meo 222 (X-8) 2-Cl, 3-n-Propyl, 5-MeO Me 5'-MeO, 6'-MeO Meo 223 (X-8) 2-Cl, 3-Propargyl, 5-MeO Me 5'-MeO, 6'-MeO Meo 224 (X-8) 2-Br, 3-Et, 5-MeO Me 5'-MeO, 6'-MeO Meo 225 (X-8) 2-Br, 3-Allyl, 5-MeO Me 5'-MeO, 6'-MeO Meo 226 (X-8) 2-Br, 3-n-Propyl, 5-MeO Me 5'-MeO, 6'-MeO Meo
ir 227 (X-8) 2-Br, 3-Propargyl, 5-MeO Me 5'-MeO, 6'-MeO Meo 228 (X-8) 3-Me, 5-Br Me 5'-MeO, 6'-MeO Meo Viscous substance 229 (X-8) 3-Et, 5-Br Me 5'-MeO, 6'-MeO Meo 230 (X-8) 3-Allyl, 5-Br Me 5'-MeO, 6'-MeO Meo 231 (X-8) 3-n-Propyl, 5-Br Me 5'-MeO, 6'-MeO Meo 232 (X-8) 3-Propargil, 5-Br Me 5'-MeO, 6'-MeO Meo 233 (X-8) 3-Me, 5-Br, 6-Cl Me 5'-MeO, 6'-MeO Meo 234 (X-8) 3-Et, 5-Br, 6-Cl Me 5'-MeO, 6'-MeO Meo

Table 34 No. Formula (X) _n R ¹ (R ² ) _p R ³ Physical properties 235 (X-8) 3-Allyl, 5-Br, 6-Cl Me 5'-MeO, 6’-MeO Meo 236 (X-8) 3-n-Propargyl, 5-Br, 6-Cl Me 5'-MeO, 6'-MeO Meo 237 (X-8) 3-Propargyl, 5-Br, 6-Cl Me 5'-MeO, 6'-MeO Meo 238 (X-8) 3-Me, 5-Br, 6-Br Me 5'-MeO, 6'-MeO Meo 239 (X-8) 3-Et, 5-Br, 6-Br Me 5'-MeO, 6'-MeO Meo 240 (X-8) 3-Allyl, 5-Br, 6-Br Me 5'-MeO, 6'-MeO Meo 241 (X-8) 3-n-Propyl, 5-Br, 6-Br Me 5'-MeO, 6'-MeO Meo 242 (X-8) 3-Propargyl, 5-Br, 6-Br Me 5'-MeO, 6'-MeO Meo 243 (X-8) 3-MeO, 5-MeO Me 5'-MeO, 6'-MeO Meo 244 (X-8) 3-MeO, 5-Cl Me 5'-MeO, 6'-MeO Meo 245 (X-8) 2-Br, 3-Cl, 5-MeO Me 5'-MeO, 6'-MeO Meo 246 (X-8) 2-Br, 3-Br, 5-Br Me 5'-MeO, 6'-MeO Meo 247 (X-8) 2-Cl, 3-Br, 5-Br Me 5'-MeO, 6'-MeO Meo 248 (X-8) 2-Br, 3-Cl, 5-Cl Me 5'-MeO, 6'-MeO Meo 249 (X-8) 2-Cl, 3-MeO, 5-Cl, 6-Cl Me 5'-MeO, 6'-MeO Meo 250 (X-8) 2-Br, 3-MeO, 5-Cl, 6-Cl Me 5'-MeO, 6'-MeO Meo 251 (X-8) 3-EtO, 5-EtO Me 5'-MeO, 6'-MeO Meo 252 (X-8) 3-EtO, 5-Cl Me 5'-MeO, 6'-MeO Meo 253 (X-8) 2-Br, 3-EtO, 5-Cl Me 5'-MeO, 6'-MeO Meo 254 (X-8) 2-Br, 3-Cl, 5-EtO Me 5'-MeO, 6'-MeO Meo 255 (X-8) 2-Cl. 3-Br, 5-EtO Me 5'-MeO, 6'-MeO Meo 256 (X-8) 2-Br, 3-Br, 5-EtO Me 5'-MeO, 6'-MeO Meo 257 (X-8) 2-Br, 3-Cl, 5-Cl Me 5'-MeO, 6'-MeO Meo 258 (X-8) 2-Cl, 3-EtO, 5-Cl, 6-Cl Me 5'-MeO, 6'-MeO Meo

Table 35 No. Formula (X) _n R ¹ (R ² ) _p R ³ Physical properties 259 (X-8) 2-Br, 3-EtO, 5-Cl, 6-Cl Me 5'-MeO, 6'-MeO Meo 260 (X-8) 2-Cl, 3-EtO, 5-Cl, 6-Br Me 5'-MeO, 6'-MeO Meo 261 (X-8) 2-Br, 3-EtO, 5-Cl, 6-Br Me 5'-MeO, 6'-MeO Meo 262 (X-8) 2-F, 3-F, 5-F, 6-F Me 5'-MeO, 6'-MeO Meo Viscous substance 263 (X-8) 2-Br, 3-F, 5-F Me 5'-MeO, 6'-MeO Meo 264 (X-8) 2-F, 3-Me, 5-F Me 5'-MeO, 6'-MeO Meo 265 (X-8) 2-Br, 3-F, 5-F, 6-Br Me 5'-MeO, 6'-MeO Meo 266 (X-8) 2-Cl, 3-F, 5-F Me 5'-MeO, 6'-MeO Meo 267 (X-8) 2-Br, 3-Br, 5-Br, 6-Br Me 5'-MeO, 6'-MeO Meo 268 (X-8) 2-Cl, 3-Cl, 5-Cl, 6-Cl Me 5'-MeO, 6'-MeO Meo 269 (X-8) 3-Br, 5-F Me 5'-MeO, 6'-MeO Meo 270 (X-8) 2-Br, 3-F, 5-F, 6-F Me 5'-MeO, 6'-MeO Meo 271 (X-8) 3-F, 5-CH ₃ Me 5'-MeO, 6'-MeO Meo 272 (X-8) 3-Cl, 5-CH ₃ Me 5'-MeO, 6'-MeO Meo 273 (X-8) 3-F, 5-MeO Me 5'-MeO, 6'-MeO Meo 274 (X-8) 2-Cl, 3-CF ₃ , 6-CF ₃ Me 5'-MeO, 6'-MeO Meo so pl. 154-158 ° C 275 (X-8) 3-CF ₃ , 6-CF ₃ Me 5'-MeO, 6'-MeO Meo 276 (X-8) 3-CF ₃ , 5-Me, 6-CF ₃ Me 5'-MeO, 6'-MeO Meo 277 (X-8) 3-CF ₃ , 5-Et, 6-CF ₃ Me 5'-MeO, 6'-MeO Meo 278 (X-8) 3-CF ₃ , 5-Allyl, 6-CF ₃ Me 5'-MeO, 6'-MeO Meo 279 (X-8) 3-CF ₃ , 5-n-Propyl, 6-CF ₃ Me 5'-MeO, 6'-MeO Meo 280 (X-8) 3-CF ₃ , 5-Propargil, 6-CF ₃ Me 5'-MeO, 6'-MeO Meo 281 (X-8) 2-Cl, 3-CF ₃ , 5-CF ₃ , 6-Cl Me 5'-MeO, 6'-MeO Meo 282 (X-8) 2-Cl, 3-CF ₃ , 5-CF ₃ Me 5'-MeO, 6'-MeO Meo

Table 36 No. Formula (X) p R ¹ (R ² ) p R ³ Physical properties 283 (X-8) 3-CF ₃ , 5-CF ₃ Me 5'-MeO, 6'-MeO Meo 284 (X-9) 3-Cl, 5-Cl, 6-Cl Me 5'-MeO, 6'-MeO Meo so pl. 97-99 ° C 285 (X-9) 3-F, 5-F, 6-F Me 5'-MeO, 6'-MeO Meo 286 (X-9) 3-Br, 5-Br Me 5'-MeO, 6'-MeO Meo so pl. 114-117 ° C 287 (X-7) 2-MeO, 4-Br, 5-Cl Me 5'-MeO, 6'-MeO Meo NMR data (table 37) 288 (X-7) 2-MeO, 4-Cl, 5-Cl Me 5'-MeO Meo NMR data (table 37) 289 (X-7) 2-MeO, 4-Cl, 5-Cl Et 5'-EtO Meo NMR data (table 37) 290 (X-7) 2-EtO, 4-Br, 5-Cl Me 5'-MeO, 6'-MeO Meo NMR data (table 37) 291 (X-7) 2-EtO, 4-Cl, 5-Br Me 5'-MeO, 6'-MeO Meo NMR data (table 37) 292 (X-7) 2-MeO, 4-Cl, 5-I Me 5'-MeO, 6'-MeO Meo NMR data (table 37) 293 (X-7) 2-MeO, 4-Br, 5-Br Me 5'-MeO, 6'-MeO Meo NMR data (table 37) 294 (X-7) 2-MeO, 4-CF ₃ , 5-Br Me 5'-MeO, 6'-MeO Meo NMR data (table 37) 295 (X-7) 2-MeO, 4-Cl, 5-Cl Me 5'-MeO, 6'-MeO Meo NMR data (table 37) 296 (X-7) 2-Cl, 4-Cl, 5-Me Me 5'-MeO, 6'-MeO Meo NMR data (table 37) 297 (X-7) 2-Cl, 4-Cl, 5-I Me 5'-MeO, 6'-MeO Meo NMR data (table 37) 298 (X-7) 2-F, 4-I, 2-Me Me 5'-MeO, 6'-MeO Meo NMR data (table 37) 299 (X-7) 2-MeO, 4-Cl, 5-Br Me 5'-MeO, 6'-MeO Meo NMR data (table 37) 300 (X-7) 2-MeO, 4-CH ₂ F, 5-Cl Me 5'-MeO, 6'-MeO Meo NMR data (table 37) 301 (X-7) 2-MeO, 4-Me, 5-Cl Me 5'-MeO Meo NMR data (table 37) 302 (X-7) 2-Cl, 4-Me, 5-Cl Me 5'-MeO, 6'-MeO Meo Pale yellow oily substance 303 (X-7) 2-Cl, 4-Me, 5-Cl Me 5'-MeO, 6'-MeO Meo NMR data (table 37) 304 (X-7) 2-Me, 5-Cl Me 5'-MeO, 6'-MeO NMR data (table 37)

Supplement to table 36: data for the compounds of table. 36

Table 36 ¹ H-NMR (CDCl ₃ , 400 MHz): δ (ppm) 287 2.33 (s, 3H), 3.46 (s, 3H), 3.77 (s, 3H), 3.82 (s, 3H), 3.94 (s, 3H), 5.33 (d , 1H, J = 10.4 Hz), 6.17 (d, 1H, J = 10.4 Hz), 6.48 (s, 1H), 8.06 (s, 1H) 288 2.42 (s, 3H), 3.70 (s, 3H), 3.77 (d, 1H, J = 11.6 Hz), 3.86 (s, 3H), 4.00 (s, 3H) ), 6.32 (d, 1H, J = 11.6 Hz), 6.58 (s, 1H), 6.72 (s, 1H), 8.18 (s, 1H) 289 1.30 (t, 3H, J = 6.8 Hz), 2.35 (s, 3H), 3.74 (d, 1H, J = 11.2 Hz), 3.78 (s, 3H), 3.86 (q, 2H, J = 6.8 Hz), 3.93 (s, 3H), 6.24 (d, 1H, J = 11.2 Hz), 6.50 (s, 1H), 6.65 (s, 1H), 8.11 (s, 1H) 290 1.41 (t, 3H, J = 4.4 Hz), 2.24 (s, 3H), 3.77 (s, 3H), 3.82 (s, 3H), 4.09 (s, 3H) ), 4.44 (q, 2H, J = 4.4 Hz), 5.36 (d, 1H, J = 9.6 Hz), 6.34 (d, 1H, J = 9.6 Hz), 6.48 (s, 1H); 7.98 (s, 1H) 291 1.35 (t, 3H, J = 4.4 Hz), 2.33 (s, 3H), 3.49 (s, 3H), 3.77 (s, 3H), 3.83 (s, 3H) ), 4.44 (q, 2H, J = 4.4 Hz), 5.38 (d, 1H, J = 10.0 Hz), 6.23 (d, 1H, J = 10.0 Hz), 6.48 (s, 1H), 8.17 (s, 1H) 292 2.34 (s, 3H), 3.51 (s, 3H), 3.77 (s, 3H), 3.82 (s, 3H), 3.95 (s, 3H), 5.31 (d , 1H, J = 10.4 Hz), 6.23 (d, 1H, J = 10.4 Hz), 6.47 (s, 1H), 8.36 (s, 1H) 293 2.24 (s, 3H), 3.53 (s, 3H), 3.77 (s, 3H), 3.83 (s, 3H), 3.97 (s, 3H), 4.50-4 65 (broad s, 1H), 6.28-6.34 (broad s, 1H), 6.48 (s, 1H), 8.16 (s, 1H) 294 2.35 (s, 3H), 3.29 (s, 3H), 3.74 (s, 3H), 3.82 (s, 3H), 3.90 (s, 3H), 4.86-4 88 (broad s, 1H), 6.19-6.22 (broad s, 1H), 6.51 (s, 1H), 8.31 (s, 1H) 295 2.32 (s, 3H), 3.52 (s, 3H), 3.77 (s, 3H), 3.82 (s, 3H), 4.11 (s, 3H), 5.32 (d , 1H, J = 10.0 Hz), 6.21 (d, 1H, J = 10.0 Hz), 6.55 (s, 1H), 8.07 (s, 1H) 296 2.10 (s, 3H), 2.26 (s, 3H), 3.59 (s, 3H), 3.73 (s, 3H), 3.77 (s, 3H), 5.15 (d , 1H, J = 9.2 Hz), 6.41 (d, 1H, J = 9.2 Hz), 6.42 (s, 1H), 8.08 (s, 1H) 297 2.18 (s, 3H), 3.62 (s, 3H), 3.76 (s, 3H), 3.81 (s, 3H), 5.02 (br s, 1H), 6.41 (broad s, 1H), 6.46 (s, 1H), 8.57 (s, 1H) 298 2.21 (s, 3H), 2.42 (s, 3H), 3.72 (s, 3H), 3.79 (s, 3H), 3.81 (s, 3H), 4.97 (d , 1H, J = 10.0 Hz), 6.07 (d, 1H, J = 10.0 Hz), 6.46 (s, 1H), 7.86 (s, 1H) 299 2.17 (s, 3H), 2.33 (s, 3H), 3.54 (s, 3H), 3.79 (s, 3H), 3.84 (s, 3H), 3.97 (s , 3H), 5.32 (d, 1H, J = 10.0 Hz), 6.23 (d, 1H, J = 10.0 Hz), 6.49 (s, 1H), 8.21 (s , 1H) 300 2.32 (s, 3H), 3.37 (s, 3H), 3.75 (s, 3H), 3.79 (s, 3H), 3.81 (s, 3H), 4.28 (d , 1H, J = 6.0 Hz), 5.59 (dd, 1H, J = 10.4 Hz, 46.8 Hz), 5.97 (dd, 1H, J = 10.4 Hz, 46.8 Hz), 6.27 (d, 1H, J = 6.0 Hz), 6.47 (s, 1H), 8.08 (s, 1H) 301 2.26 (s, 3H), 2.38 (s, 3H), 3.69 (s, 3H), 3.85 (br., 1H), 3.87 (s, 3H), 4.00 ( s, 3H), 6.13 (s, 1H), 6.57 (s, 1H), 6.72 (s, 1H), 8.11 (s, 1H) 303 2.18 (s, 3H), 2.50 (s, 3H), 3.59 (s, 3H), 3.81 (s, 3H), 3.85 (s, 3H), 6.42 (broad ., 1H), 6.50 (s, 1H), 8.26 (s, 1H) 304 2.25 (s, 3H), 2.50 (s, 3H), 3.64 (s, 3H), 3.81 (s, 3H), 3.87 (s, 3H), 5.98 (d , J = 7.6 Hz, 1H), 6.52 (s, 1H), 7.75 (s, 1H), 8.37 (d, J = 2.4 Hz, 1H)

The benzoylpyridine derivative represented by the formula (I) or a salt thereof can be used as an active ingredient or fungicide, especially as an active ingredient for agricultural and horticultural fungicides. As an agricultural and horticultural fungicide, it is effective in controlling diseases such as pyriculariosis, brown spotting or rhizoctonia of rice vaginas (Oryza sativa); powdery mildew, scab, rust, snow mold, dusty smut, eye spotting, leaf spotting or spotting of barley flakes (Hordeum vulgare); citrus melanosis or scab (Citrus); gray rot, powdery mildew, alternaria leaf spot or scab of apples (Malus pumila); scab or black spotted pears (Pyrus serotina, Pyrus ussuriensis, Pyrus coiroiunis); rhizoctonia, scab, or rot of peaches (Prunus persica) caused by the causative agent Fomitopsis; Anthracnose, glomerella rot, powdery mildew or downy mildew of grapes (Vitis vinifera); Anthracnose or circular spotting of Japanese persimmon leaves (Diospyros kaki); Anthracnose, powdery mildew, black mycospheresis rot or powdery mildew of pumpkin (Cucumis melo); brown spotting, leaf mold or late blight of tomatoes (Lycopersicon esculentum); cress spotting (Brassica sp., Raphanus sp., etc); brown spotting or late blight of potato (Solanum tuberosum); powdery mildew of strawberries (Fragaria chiloensis); gray mold or stem rot of various cereals. It has an excellent effect, especially in the fight against powdery mildew of barley and vegetables and rice pyricularosis. In addition, it is also effective in controlling soil diseases caused by phytopathogenic fungi, such as Fusarium, Pythium, Rhizoctonia, Verticillium and Plasmodiophora.

The compound of the present invention can be used in combination with agricultural excipients to obtain various preparations of fungicides containing this compound, such as dusts, granules, granular wettable powders, wettable powders, aqueous suspensions, oil suspensions, water-soluble powders, emulsifiable concentrates, aqueous solutions, pastes, aerosols or microdoses of dusts. The compound of the present invention can be prepared in the form of any preparations that are usually used in agriculture or horticulture, if only the objectives of the present invention are satisfied. As auxiliary substances that can be used to prepare preparations, one can mention, for example, a solid carrier, such as diatomaceous earth, fluffy lime, calcium carbonate, talc, white soot, kaolin, bentonite, a mixture of kaolin and serecite, clay, sodium carbonate , sodium bicarbonate, Glauber's salt, zeolites or starch; solvents such as water, toluene, xylene, naphtha, dioxane, acetone, isophorone, methyl isobutyl ketone, chlorobenzene, cyclohexane, dimethyl sulfoxide, dimethylformamide, dimethylacetamide, N-methyl-2-pyrrolidone or alcohol; anionic surfactants or distribution agents, such as fatty acid salts, benzoates, alkyl sulfosuccinates, dialkyl sulfosuccinates, polycarboxylates, salts of alkyl sulfuric esters, alkyl sulfates, alkyl aryl sulfates, alkyl diglycol ether sulfates, alkyl sulfonate esters, alkyl sulfate esters , arylsulfonates, ligninsulfonates, alkyl diphenyl ether disulfonates, polystyrene sulfonates, salts of alkyl phosphoric esters, alkylaryl veils, styryl aryl phosphates, a salt of a sulfuric acid ester and a polyoxyethylene alkyl ether, a sulfate polyoxyethylene alkyl aryl ether, a salt of a sulfuric acid ester and a polyoxyethylene alkyl aryl ether, a phosphate polyoxyethylene alkyl ether or a polyoxyethylene alkyl aryl sulfonate salt and formalin; nonionic surfactants or distribution agents, such as sorbitan fatty acid esters, glycerol fatty acid esters, polyglycerides of fatty acids, ethers of polyglycols and alcohols derived from fatty acids, acetylene glycols, acetylene alcohols, hydroxyalkylene block polymers, polyoxyethylene polyethylene -alkylaryl ethers, polyoxyethylene-styrylaryl ethers, polyoxyethylene glycol alkyl ethers, polyoxyethylene fatty acid esters, olioksietilensorbitanovye fatty acid esters, polyoxyethylene fatty acid esters, polyoxyethylene hardened castor oil or a polyoxypropylene fatty acid ester; vegetable oils or mineral oils, such as olive oil, kapok oil, castor oil, palm oil, camellia oil, coconut oil, sesame oil, corn oil, rice oil, peanut oil, cottonseed oil, linseed oil, tung oil, or liquid paraffin. Known excipients can be selected from excipients that are known in the field of agriculture and horticulture, without going beyond the scope of the present invention. Additionally, adjuvants that are commonly used may be used, such as bulking agents, thickening agents, anti-precipitation agents, anti-freezing agents, dispersion stabilizers, plant damage reducing agents, or powdery mildew protecting agents. Typically, the ratio in the mixture of the compound of the present invention to the excipient is from 0.005: 99.995 to 95: 5, preferably from 0.2: 99.8 to 90:10. Such compositions in practice can be used either as they are, or when diluted with a diluent, such as water, to the desired concentrations, and if necessary, a spray agent is added to them. The concentration of the compound of the present invention varies depending on the plants to be treated, the method of application, the form of the preparation or the dose and, therefore, cannot be indicated in the general case. However, in the case of foliar concentration of the compound as an active ingredient is usually from 0.1 to 10000 million ^-1, preferably from 1 to 2000 million ^-1. In the case of tillage, the concentration is usually from 10 to 100,000 g / ha, preferably from 200 to 20,000 g / ha.

A fungicide preparation containing a compound of the present invention, or a diluted product thereof, can be applied by any of the commonly used application methods, such as dispersion (dispersion, spraying, fogging, atomizing fine particles, spreading in the form of grains or applying to water), application to the soil (e.g. mixing or irrigation) or applying to the surface (for example, by coating, dusting or coating the surface). In addition, it can be applied using the so-called ultra-small volumes. With this method, the preparation may contain 100% of the active ingredient.

The fungicide of the present invention can be mixed or used, for example, together with another agricultural chemical such as an insecticide, miticide, nematicide, fungicide, antiviral agent, attractant, herbicide or plant growth regulator. Sometimes in this case an even more significant effect can be achieved.

Examples of compounds are active ingredients (generic name; including the compounds in question), insecticides, miticides or nematicides, i.e. pesticides from the above agricultural chemicals include organic phosphorus compounds such as profenofos, dichlorophos, fenamiphos, phenytrotion, EPN, diazinon, chlorpyrifos-methyl, acefate, prothiophos, fostiazate, phosphocarb, cadusafos and dislufoton;

carbamate-type compounds such as carbaryl, propoxur, aldicarb, carbofuran, thiodicarb, methomyl, oxamyl, etiofencarb, pyrimicarb, phenobucarb, carbosulfan and benfuracarb;

non-acetoxin derivatives such as cartap and thiocyclam;

organic chlorine compounds such as dicofol and tetradiphone;

organic metal compounds such as phenbutatin oxide;

pyrethroid compounds such as phenvalerate, permethrin, cypermethrin, deltamethrin, cygalotrin, teflutrin, etofenprox and flufenprox;

benzoylurea-type compounds such as diflubenzuron, chlorofluazuron, teflubenzuron and flufenoxuron;

compounds like juvenile hormone such as metoprene;

pyridazinone-type compounds such as pyridaben;

pyrazole-type compounds such as fenpiroximate, fipronil, tebufenpyrad, etiprol, tolfenpyrad and acetoprol;

neonicotinoids such as imidacloprid, nitenpyram, acetamipride, thiacloprid, thiamethoxam, clothianidin, nidinotefuran and dinotefuran;

compounds such as hydrazine, such as tebufenoside, methoxyphenoside and chromafenoside;

pyridine type compounds such as pyridaryl and flonicamide;

tetronic acid type compounds such as spirodiclofen;

compounds such as strobilurin, such as fluacripirin;

dinitro compounds, organic sulfur compounds, urea-type compounds, triazine-type compounds, hydrazone-type compounds and other compounds such as buprofesin, hexithiazox, amitraz, chlordimeform, silafluofen, triazamate, pymetrozine, pyrimidiphene, chlorfenapyr, indoxacarbazole, acecholazine, acecholazine, acecholazine, acechine 3-dichloropropene; AKD-1022 and IKA-2000. In addition, the fungicide of the present invention can be mixed or used with a microbial pesticide, such as BT, or with a pathogenic insect virus, or with an antibiotic, such as avermectin, milbemycin, spinosad or emamectin benzoate.

Among other agricultural chemicals, examples of the active ingredient compounds of the fungicides (common name; including the subject compounds) include pyrimidinamine type compounds such as mepanipyrim, pyrimethanil and cyprodinil, pyridinamine type compounds such as fluazinam;

compounds of the azole type, such as triadimefon, bitertanol, triflumezole, ethaconazole, propiconazole, penconazole, fluzilazole, miclobutanyl, ciproconazole, terbukonazole, hexaconazole, furconazole-cis, prochloraz, metconazole, epicazole;

quinoxaline type compounds such as quinomethionate;

compounds of the dithiocarbamate type, such as maneb, kineb, mankozeb, polycarbamate, metiram and propineb; or

organic chlorine compounds such as phthalide, chlorothalonil and chintosene;

compounds of the imidazole type, such as benomyl, thiofanate methyl, carbendazim and cyazofamide;

compounds such as cyanoacetamide such as cymoxanil;

compounds of the phenylamide type, such as metalaxyl, metalaxyl M, oxadixyl, ofuras, benalaxyl, furalaxyl and ciprofuram;

sulfenic acid type compounds such as dichlorofluanide;

copper compounds such as copper hydroxide and Oxine Copper;

compounds of the isoxazole type, such as hydroxyisoxazole;

organophosphorus compounds such as fosetyl-Al, tolkofos-methyl, 3-benzyl O, O-diisopropylphosphorothioate, O-ethyl S, S-diphenylphosphorodithioate and aluminum ethyl hydrophosphonate;

N-halogenioalkyl type compounds such as captan and folpet;

compounds of the dicarboxyimide type, such as procymidone, iprodione and vinclozolin;

benzaniline-type compounds such as flutolanil, mepronil and zoxamide;

piperazine type compounds such as triforin;

pyridine type compounds such as pyrifenox;

carbinol type compounds such as fenarimol and flutriafol;

compounds such as piperidine, fenpropidin;

compounds of the morpholine type, such as fenpropimorph;

organotin compounds such as fentin hydroxide and fentin acetate;

urea-type compounds such as phencycuron;

cinnamic acid type compounds such as dimethomorph;

carbamate-type compounds such as diethophencarb;

cyanopyrrole type compounds such as fludioxonil and fenpiclonil;

compounds such as strobilurin, such as azoxystrobin, kresoxime-methyl, metominophen, trifluoxystrobin, picoxystrobinipirachlostrobin: (BAS 500F);

compounds such as oxazolidinone, such as famoxadone;

thiazolecarboxamide-type compounds such as ethaboxam;

compounds such as silylamide, such as silthiofam;

amino acid amide carbamate-type compounds such as iprivalicarb and bentiavalicarb;

compounds such as imidazolidine, such as phenamidone;

hydroxyanilide-type compounds such as phenhexamide;

benzenesulfonamide-type compounds such as flusulfamide;

compounds such as oxime esters, such as cyflufenamide;

compounds of the phenoxyamide type, such as phenoxanil;

compounds of the triazole type, such as simeconazole;

compounds such as anthraquinone; compounds of the type crotonic acid; antibiotics and other compounds, such as isoprothiolan, tricyclazole, pyrochilone, diclomesin. Pro. benzene, quinoxifene, propamocarbhydrochloride, spiroxamine, chloropicrin, dazomet and metham sodium; and BJL-993, BJL-994, BAS-510, BAS-505, MTF-753 and UIBF-307.

The following are test examples for the agricultural and horticultural fungicides of the present invention. However, these examples in no way limit the present invention.

In each of the tests, an indicator of the effectiveness of suppressing diseases (control indicator) is determined based on the following criteria.

[control score]: [Degree of outbreak: visual observation]

5: Neither lesions nor sporogony are noticeable

4: Area of lesion, number of lesions or sporogony area is less than 10% of the corresponding values for untreated specimens

3: Area of lesion, number of lesions or sporogony area is less than 40% of the corresponding values for untreated specimens

2: Area of lesion, number of lesions, or sporogony area is less than 70% of the corresponding values for untreated specimens

1: Area of lesion, number of lesions, or sporogony area is at least 70% of the corresponding values for untreated specimens.

TEST EXAMPLE 1

Test to determine the protective effect against real powdery mildew of wheat

Wheat (cultivar Norin-61-go) is grown in plastic pots with a diameter of 7.5 cm, and when the wheat reaches the stage of one and a half leaves, it is sprayed with 10 ml of a solution containing a certain concentration of the compound of the present invention using a sprayer. After the solution has dried, the wheat is infected by applying the conidiospores of the powdery mildew fungus, then the wheat is kept in a thermostatic chamber at 20 ° C. 6-8 days after inoculation, the sporogony area is examined to determine the control index using the above criteria. As a result, the above compounds No. 1, 2, 8, 47, 58, 61, 62, 69, 73, 76, 77, 78, 83, 87, 91, 107, 110, 112, 114, 117, 119, 138 , 250, 262 and 274 showed the results corresponding to parameters controlling 4 or above at a concentration of 500 million ^-1 and compound №№3, 4, 5, 6, 7, 9, 10, 11, 13, 14, 18, 19, 23, 27, 30, 31, 32, 33, 34, 35, 36, 38, 40, 41, 43, 49, 50, 51, 54, 55, 56, 59, 65, 72, 74, 75, 82, 84, 89, 90, 92, 93, 94, 99, 100, 101, 102, 103, 104, 105, 106, 108, 109, 111, 113, 118, 120, 121, 122, 123, 124, 133, 136, 142, 158, 159, 186, 187, 188, 189, 190 191, 192, 193, 194, 199, 200, 210, 211, 213, 228, 243, 245, 249 252, 254, 272, 287, 288, 289, 290, 291, 292, 293, 294, 296, 297, 298, 299, 300, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 320 and 321 showed results you corresponding control parameters of 4 or above at a concentration of 125 million ^-1.

TEST EXAMPLE 2

Test to determine the protective effect against rice pyriculariosis

Rice (cultivar: Nihonbare) is grown in 7.5 cm diameter plastic pots, and when the rice reaches the stage of one and a half leaves, it is sprayed with 10 ml of a solution containing a certain concentration of the compound of the present invention using a sprayer. After the solution has dried, the rice is infected by applying a suspension of conidiospores of rice pyriculariosis fungus, then the rice is kept in the inoculation box at 20 ° C for 24 hours, and then kept in a thermostatic chamber at 20 ° C. 6-11 days after inoculation, the number of affected areas is examined to determine a control index using the above criteria. As a result of the above compounds, compounds No. 31, 56, 76, 90, 103, 136, 158, 293, 294, 307, 308, 309, 314, 315, 316 and 321 showed results corresponding to control values of 4 or higher at a concentration of 500 million ^-1, and compounds №№50, 74, 75 and 102 showed results corresponding control parameters of 4 or above at a concentration of 125 million ^-1.

TEST EXAMPLE 3

Test to determine the protective effect against real powdery mildew of eggplant

Eggplant (grade Senryo-2-go) is grown in 7.5 cm diameter plastic pots, and when the eggplant plants reach the two-leaf stage, they are sprayed with 10 ml of a solution containing a certain concentration of the compound of the present invention using a sprayer. After the solution has dried, the eggplants are infected by applying the conidiospores of the real powdery mildew of eggplant, then the eggplants are kept in a thermostatic chamber at 20 ° C. 16 days after inoculation, the sporogony area is examined to determine a control index using the above criteria. As a result of the above compounds, compounds №№1, 3, 5, 7, 92, 101 and 103 showed results corresponding control parameters of 4 or above at a concentration of 500 million ^-1 and compound №№9, 11, 55, 90 and 102 demonstrated the results corresponding to the control parameters of 4 or above at a concentration of 125 million ^-1.

TEST EXAMPLE 4

Test to determine the protective effect against real powdery mildew of cucumbers

Cucumbers (Suyo variety) are grown in 7.5 cm diameter plastic pots, and when the cucumbers reach the stage of one and a half leaves, they are sprayed with 10 ml of a solution containing a certain concentration of the compound of the present invention using a sprayer. After the solution has dried, the cucumbers are infected by applying a suspension of conidiospores of powdery mildew fungus, then the cucumbers are kept in a thermostatic chamber at 20 ° C. 7-11 days after inoculation, the sporogony area is examined to determine a control index using the above criteria. As a result of the above compounds, the compound has demonstrated №98 results corresponding control indicators 4 or above at a concentration of 500 million ^-1, and compounds №№1, 5, 7, 9, 49, 55, 74, 90, 92, 93, 102 , 103, 123, 124, 158, 159, 293, 294, 296, 297, 299, 300, 302, 303, 304, 305, 306, 307, 308, 313, 314, 315, 316 and 321 showed results corresponding to control indicators 4 or above at a concentration of 125 million ^-1.

The following are examples of compositions containing the compounds of the present invention. However, the examples cited in no way limit the dosage of the compositions, dosage form, and the like.

EXAMPLE OF COMPOSITION 1

(1) The compound of the present invention 20 weight. parts

(2) Clay 72 weight. parts

(3) Sodium ligninsulfonate 8 weight. parts

The above components are mixed until uniform, obtaining a wettable powder.

EXAMPLE OF COMPOSITION 2

(1) The compound of the present invention 5 weight. parts

(2) Talc 95 weight. parts

The above components are mixed until homogeneous, receiving dust.

EXAMPLE OF COMPOSITION 3

(1) The compound of the present invention 20 weight. parts

(2) N, N-dimethylacetamide 20 weight. parts

(3) Alkylphenyl ether of polyoxyethylene 10 wt. parts

(4) Xylene 50 weight. parts

The above components are mixed until homogeneous and dissolved to obtain an emulsifiable concentrate.

EXAMPLE OF COMPOSITION 4

(1) Clay 68 weight. parts

(2) Sodium lignin sulfonate 2 parts by weight

(3) Polyoxyethylene alkylaryl sulfate 5 wt. parts

(4) Fine Silica 25 wt. parts

A mixture of the above components and the compound of the present invention are mixed in a 4: 1 weight ratio to obtain a wettable powder.

EXAMPLE OF COMPOSITION 5

(1) The compound of the present invention 50 wt. parts

(2) Oxidized Polyalkylphenyl Phosphate-Triethanolamine 2 parts by weight

(3) Silicone 0.2 weight. parts

(4) Water 47.8 weight. parts

The above components are mixed until homogeneous and ground to obtain a stock solution, and then added to it

(5) Sodium polycarboxylate 5 wt. parts

(6) Anhydrous sodium sulfate 42.8 weight. parts

Then everything is mixed until smooth, granulated and dried, obtaining a granular wettable powder.

EXAMPLE OF COMPOSITION 6

(1) The compound of the present invention 5 weight. parts

(2) Polyoxyethylene-octylphenyl ether 1 weight. part

(3) Polyoxyethylene phosphate 0.1 wt. parts

(4) Ground calcium carbonate 93.9 weight. parts

The above components (1) to (3) are pre-mixed until homogeneous and diluted with an appropriate amount of acetone, component (4) is sprayed with the diluted mixture and the acetone is removed to obtain granules.

EXAMPLE OF COMPOSITION 7

(1) The compound of the present invention 2.5 weight. parts

(2) N-methyl-2-pyrrolidone 2.5 weight. parts

(3) Soybean oil 95.0 weight. parts

The above components are mixed until homogeneous and dissolved, obtaining a composition of ultra-small volume.

EXAMPLE OF COMPOSITION 8

(1) The compound of the present invention 20 weight. parts

(2) Oxidized polyalkylphenolphosphate-triethanolamine 2 wt. parts

(3) Silicone 0.2 weight. parts

(4) Xanthan gum 0.1 weight. parts

(5) Ethylene glycol 5 weight. parts

(6) Water 72.7 weight. parts

The above components are mixed to homogeneity and crushed to obtain an aqueous suspension.

Industrial applicability

As indicated above, the benzoylpyridine derivatives represented by the formula (I) or their salts have excellent action as the active ingredient of the fungicides.

Claims (17)

1. Derived benzoylpyridine represented by formula (I), or its salt

where X represents a halogen atom, a C _1-6 alkoxy group optionally substituted with a substituent selected from halogen, phenyl, methoxy, methylthio, dimethylamino, vinyl and ethinyl; phenoxy group; C _3-6 cycloalkoxy; hydroxyl group; A C _1-6 alkyl group; C _2-6 alkenyl group; CF ₃ group; C _1-6 alkylthio; cyano group; C _1-6 alkoxycarbonyl group; C _1-6 dialkylaminocarbonyl group; A C _1-6 alkylcarbonyloxy group; A C _1-6 alkylcarbonyl group; an amino group; A C _1-4 alkylamino group; or di-C _1-4 alkylamino group; n represents 1, 2, 3 or 4; R ¹ represents a C _1-6 alkyl group; R ² represents a C _1-6 alkyl group; C _1-6 alkoxy optionally substituted with phenyl; phenoxy group; C _3-10 cycloalkoxy or hydroxyl group; and m is 1, 2 or 3, provided that if m is 2, then R ² can form a -OCH ₂ O- ring (unless the pyridine ring is substituted with a benzoyl group in the 2-position; the pyridine ring is substituted with C _{1 -6} alkoxy group, hydroxyl group or benzyloxy group at the 3-position; and n is 1, m is 1 or 2) as an active ingredient of fungicide. 2. The benzoylpyridine derivative or its salt according to claim 1 as the active ingredient of the fungicide, where X is a halogen atom, a C _1-6 alkoxy group optionally substituted with a substituent selected from halogen, phenyl, methoxy, methylthio, dimethylamino, vinyl and ethinyl; phenoxy group; C _3-6 cycloalkoxy; hydroxyl group; A C _1-6 alkyl group; C _3-6 alkenyl group; CF ₃ group; C _1-6 alkylthio; a cyano group or an amino group; C _1-4 alkylamino; di-C _1-4 alkylamino group. 3. The benzoylpyridine derivative or its salt according to claim 1 as the active ingredient of the fungicide, where m is 2 or 3. 4. The benzoylpyridine derivative or its salt according to claim 1 as the active ingredient of the fungicide, where R ¹ represents a C _1-6 alkyl group and R ² represents a C _1-6 alkyl group, a C _1-6 alkoxy group or a hydroxyl group. 5. Derived benzoylpyridine or its salt according to claim 1, represented by formula (I ')

where X, n and R ¹ have the meanings indicated in claim 1, R ^{2 ′} represents a C _1-6 alkyl group, a C _1-6 alkoxy group, a phenoxy group, a C _3-10 cycloalkoxy group or a hydroxyl group, p is 1 or 2, and R ^{2 ″} represents a C _1-6 alkoxy group or a hydroxyl group, provided that two of R ^{2 ″} and R ^{2 ″} may form a —OCH ₂ O— ring (unless (1) the pyridine ring is substituted with a group benzoyl at 2-position; the pyridine ring is substituted by a C _1-6 alkoxy group, a hydroxyl group or a benzyloxy group at the 3-position; and n is 1, p is 1, and (2) pyridines e ring is substituted by a chlorine atom or a bromine atom in the 2-position and n is 1). 6. A benzoylpyridine derivative or a salt thereof according to claim 5, represented by formula (I ″)

where X represents a halogen atom, a C _1-6 alkoxy group optionally substituted with a substituent selected from halogen, phenyl, methoxy, methylthio, dimethylamino, vinyl and ethinyl; phenoxy group, C _3-10 cycloalkoxy group, C _1-6 alkylthio group, cyano group, C _1-6 alkoxycarboxyl group, C _1-6 dialkylaminocarbonyl group, C _1-6 alkylcarbonyloxy group, C _1-6 alkylcarbonyl group, amino group, C _{1 A -4} alkylamino group or a di-C _1-4 alkylamino group; n is 1, 2, 3 or 4; R ¹ represents a C _1-6 alkyl group; R ^{2 ′} represents a C _1-6 alkoxy group; p is 1 or 2; and each of R ^{2 ″} and R ^{2 ″ ″} represents a C _1-6 alkoxy group. 7. The benzoylpyridine derivative or its salt according to claim 5, represented by the formula (I ″)

where X represents a halogen atom, a C _1-6 alkoxy group, a C _1-6 alkyl group, a CF ₃ group or a C _1-6 alkylthio group; n is 1, 2, 3 or 4; R ¹ represents a C _1-6 alkyl group; R ^{2 ′} represents a C _1-6 alkoxy group; p is 1 or 2; and each of R ^{2 ″} and R ^{2 ″ ″} represents a C _1-6 alkoxy group. 8. The benzoylpyridine derivative or its salt according to claim 5, represented by the formula (I ″ ″)

where X represents a halogen atom, a C _1-6 alkoxy group, a C _1-6 alkyl group, a CF ₃ group or a C _1-6 alkylthio group; n is 1, 2 or 3; R ¹ represents a C _1-6 alkyl group; R ^{2 '} represents a C _1-6 alkoxy group, p is 1 or 2; and each of R ^{2 ″} and R ^{2 ″ ″} represents a C _1-6 alkoxy group. 9. Derived benzoylpyridine or its salt according to claim 8, represented by the formula (I '' '' ')

where B is —CX ⁴ =, if A is —N =; B is —N = if A is —CH =; each of X ¹ and X ² which are independent of each other, represents a halogen atom, a C _1-6 alkoxy group, a C _1-6 alkyl group, a CF ₃ group or a C _1-6 alkylthio group; X ³ represents a hydrogen atom, a halogen atom, a C _1-6 alkoxy group or a C _1-6 alkyl group; X ⁴ represents a hydrogen atom, a halogen atom, a C _1-6 alkoxy group or a C _1-6 alkylthio group; R ¹ represents a C _1-6 alkyl group; R ^{2 ′} represents a C _1-6 alkoxy group; p is 1 or 2; and each of R ^{2 ″} and R ^{2 ″ ″} represents a C _1-6 alkoxy group. 10. A fungicide that contains as an active ingredient a benzoylpyridine derivative represented by the formula (I '), or a salt thereof according to claim 5. 11. A method of obtaining a benzoylpyridine derivative represented by the formula (I '), or a salt thereof

where X, n and R ¹ have the meanings indicated in claim 1, R ^{2 ′} represents a C _1-6 alkyl group, a C _1-6 alkoxy group, a phenoxy group, a C _3-10 cycloalkoxy group or a hydroxyl group; p is 1 or 2, and R ^{2 ″} represents a C _1-6 alkoxy group or a hydroxyl group, provided that two of R ^{2 ’} and R ^{2 ″} can form a —OCH ₂ O— ring (unless pyridine the ring is substituted with a benzoyl group at the 2-position; the pyridine ring is substituted with a C _1-6 alkoxy group, a hydroxyl group or a benzyloxy group at the 3-position; and n is 1, p is 1), which includes the reaction of a substituted benzaldehyde represented by the formula (VI-1 )

(where R ¹ , R ^{2 ′} , R ^{2 ″} and p are as defined above), and salts of a substituted pyridine derivative with a metal represented by the formula (VII-1)

(where X has the above meanings, and Z represents a metal atom or its mixed salt) to obtain phenylpyridylmethanol represented by the formula (X ')

(where X, n, p, R ¹ , R ^{2 '} and R ^2' have the above meanings, subject to the conditions specified for formula (I ')), and its oxidation. 12. A method of obtaining a benzoylpyridine derivative represented by the formula (I '), or its salt

where X, n and R ¹ have the meanings indicated in claim 1; R ^{2 ′} represents a C _1-6 alkyl group, a C _1-6 alkoxy group, a phenoxy group, a C _3-6 cycloalkoxy group or a hydroxyl group; p is 1 or 2, and R ^{2 ″} represents a C _1-6 alkoxy group or a hydroxyl group; with the proviso that two R ^{2 ′} and R ^{2 ″} may form a -OCH ₂ O- ring (unless the pyridine ring is substituted with a 2-position benzoyl group; the pyridine ring is substituted with a C _1-6 alkoxy group, a hydroxyl group, or - benzyloxy at the 3-position; and n is 1, p is 1), which includes reacting a salt of a substituted benzene derivative with a metal represented by the formula (VI-2)

(where R ¹ , R ^{2 '} and p have the above meanings, and Z represents a metal atom or its mixed salt), and substituted pyridylaldehyde represented by the formula (VII-2)

(where X has the above meanings), to obtain phenylpyridylmethanol represented by the formula (X ')

(where X, n, p, R ¹ R ^{2 '} and R ^2' have the above meanings, subject to the conditions specified for formula (I ')), and its oxidation. 13. Phenylpyridylmethanol represented by the formula (X)

where X represents a halogen atom, a C _1-6 alkoxy group, a C _1-6 alkyl group, a C _2-6 alkenyl group, a CF ₃ group; or a C _1-6 alkoxycarbonyl group; n is 1, 2, 3 or 4; R ¹ represents a C _1-4 alkyl group; R ² represents a C _1-4 alkyl group, a C _1-6 alkoxy group, a C _3-10 cycloalkoxy group, or two R ² located at positions 4 and 5 form a —OCH ₂ O— group; and m is 1, 2 or 3, (unless the pyridine ring is substituted with an α-hydroxybenzyl group at the 2-position; the pyridine ring is replaced with a C _1-6 alkoxy group at the 3-position; and n is 1, m is 1 or 2 ) 14. Phenylpyridylmethanol according to item 13, represented by the formula (X ')

where X, n and R ¹ have the meanings indicated in paragraph 13, R ^{2 '} represents a C _1-4 alkyl group, a C _1-6 alkoxy group, or a C _3-10 cycloalkoxy group; p is 1 or 2, and R ^{2 ″} represents a C _1-6 alkoxy group, with the proviso that two R ^{2 ″} and R ^{2 ″} can form a group (—OCH ₂ O—) (unless the pyridine ring is substituted α-hydroxybenzyl group at the 2-position; the pyridine ring is substituted with a C _1-6 alkoxy group at the 3-position; and n is 1, p is 1). 15. Phenylpyridylmethanol according to claim 14, represented by formula (X ″)

where X represents a halogen atom, a C _1-6 alkoxy group, a C _1-4 alkyl group, a C _2-6 alkenyl group, a CF ₃ group; With a _1-6 alkoxycarbonyl group, n is 1, 2, 3 or 4; R ¹ represents a C _1-4 alkyl group; R ^{2 ′} represents a C _1-6 alkoxy group, p is 1 or 2, and each of R ^{2 ″} and R ^{2 ″ ″} represents a C _1-6 alkoxy group. 16. Phenylpyridylmethanol according to claim 14, represented by formula (X ″ ″)

where X represents a halogen atom, a C _1-6 alkoxy group, a C _1-4 alkyl group or a CF ₃ group; n is 1, 2, 3 or 4; R ¹ represents a C _1-4 alkyl group; R ^{2 ′} represents a C _1-6 alkoxy group; p is 1 or 2; and each of R ^{2 ″} and R ^{2 ″ ″} represents a C _1-6 alkoxy group. 17. Phenylpyridylmethanol according to clause 16, represented by the formula (X '' '' ')

where B is —CX ⁴ = if A is —N =; B is —N = if A is —CH =; each of X ¹ and X ² that are independent of each other, represents a halogen atom, a C _1-6 alkoxy group, a C _1-4 alkyl group or a CF ₃ group; X ³ represents a halogen atom or a CF ₃ group; X ⁴ represents a hydrogen atom or a halogen atom; R ¹ represents a C _1-4 alkyl group; R ^{2 ′} represents a C _1-6 alkoxy group; p is 1 or 2; and each of R ^{2 ″} and R ^{2 ″ ″} represents a C _1-6 alkoxy group.