AP1286A

AP1286A - Benzoylpyridine derivative or its salt, Fungicide containing it as an active ingredient, its production process and intermediate for producing it.

Info

Publication number: AP1286A
Application number: APAP/P/2002/002683A
Authority: AP
Inventors: Hisaya Nishide; Munekazu Ogawa; Hidemasa Kominami; Koji Higuchi; Akihiro Nishimura
Original assignee: Ishihara Sangyo Kaisha
Priority date: 2000-07-05
Filing date: 2001-07-05
Publication date: 2004-06-26
Also published as: AP2002002683A0; ME00171B

Abstract

The present invention relates to a fungicide containing a novel benzoylpyridine derivative or its salt. The present invention provides a fungicide containing a benzoylpyridine derivative represented by the formula (I) or its salt: wherein X is a halogen atom, a nitro group, a substitutable alkoxy group, a substitutable alkoxy group, a substitutable aryloxy group, a substitutable cycloalkoxy group, a hydroxyl group, a substitutable hydrocarbon group, a substitutable alkylthio group, a cyano group, a carboxyl group which may be esterified or amidated, or a substitutable amino group; n is 1, 2, 3, or 4; R1 is a substitutable alkyl group; R2 is a substitutable alkyl group, a substitutable alkoxy group, a substitutable aryloxy group, a substitutable cycloalkoxy group or a hydroxyl group; and m is 1, 2, 3 or 4, provided that when m is at least 2, R2 may contain an oxygen atom to form a condensed ring.

Description

DESCRIPTION

BENZOYLPYRIDINE DERIVATIVE OR ITS SALT, FUNGICIDE

CONTAINING IT AS AN ACTIVE INGREDIENT, ITS PRODUCTION

PROCESS AND INTERMEDIATE FOR PRODUCING IT

TECHNICAL FIELD

The present invention relates to a novel benzoylpyridine derivative or its salt, a fungicide containing it as an active ingredient, its production process and an intermediate for producing it.

¹⁰ BACKGROUND ART

Benzoylpyridine derivatives which are analogous to the compounds of the present invention may be compounds as disclosed in e.g. WO99/41237, WO99/38845, WO96/17829, JP-A-7-309837 and JP-A-2-275858. However, they are different from the compounds of the present invention. Further, the purposes of use of these compounds are different from those of the compounds of the present invention.

Many fungicides which have been conventionally provided have their own characteristics in their controlling effects over pests which cause plant diseases. Some have a slightly poorer curative effect as compared with a preventive effect, and some have a residual effect which lasts only for a relatively short period of time, so that their controlling effects against pests tend to be practically insufficient in some cases. Accordingly, it has been desired to develop a novel compound which has a strong controlling effect against pests which cause plant diseases.

DISCLOSURE OF THE INVENTION

The present inventors have conducted extensive 5 studies to overcome the above problems and as a result, have found that use of the compound represented by the formula (I) as an active ingredient presents excellent preventive effect and curative effect against various plant diseases, particularly powdery mildew of barley, vegetables, fruits and flowering plants, and the present invention has been accomplished.

Namely, the present invention relates to a benzoylpyridine derivative represented by the formula (I)

rc <&·«,

7‘·.

wherein X is a halogen atom, a nitro group, a substitutable alkoxy’ group, a substitutable aryloxy group, a substitutable cycloalkoxy group, a hydroxyl group, a substitutable hydrocarbon group, a substitutable alkylthio group, a cyano group, a carboxyl group which may be esterified or amidated, or a substitutable amino group; n is 1, 2, 3 ox 4; r¹ is a substitutable alkyl group; R is a substitutable alkyl group, a substitutable alkoxy group, a substitutable aryloxy group, a substitutable cycloalkoxy group or a hydroxyl group; and m is 1, 2, 3 or 4, provided that when m is at least 2, R²may contain an oxygen atom to form a condensed ring (excluding a case where the pyridine ring is substituted by a benzoyl group at the 2-position; the pyridine ring is substituted by 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, its production process and an intermediate for producing it.

The halogen atom represented by X may, for example, be fluorine, chlorine, bromine or iodine, and preferably fluorine, chlorine or bromine, may, for example, be used.

The alkoxy moiety in the substitutable alkoxy group represented by each of X and R² may, for example, be a Ci_s alkoxy (such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy or t-butoxy), and preferably it may, for example, be a Ci_₄ alkoxy (such as methoxy or ethoxy) . Further, the secondary substituent of the substitutable alkoxy group may be from one to five substituents which are the same or different, selected from the group consisting of an aryl, an aryloxy, hydroxyl, nitro, nitroxy, a halogen (such as fluorine, chlorine, bromine or iodine) , a haloalkoxy (such as a Ci_₄ haloalkoxy such as CF₃O or HCF₂O) , a cycloalkyi, amino, an alkylthio and cyano. Of these substitutable alkoxy groups, preferred is an alkoxy group which is not substituted, particularly r* w

•

CM

O m·»,.

CM

preferred is a C 3.-.4 alkoxy group.

As the aryl moiety in the substitutable aryloxy group represented by X, a condensation type polycyclic group such as naphthyl as well as phenyl may be mentioned, and preferred is phenyl. The secondarysubstituent of the substitutable aryloxy group may, for example, be a halogen, an alkyl, an alkoxy or hydroxyl.

Of these substitutable aryloxy groups, most preferred is a phenoxy group.

The cycloalkyl moiety in the substitutable cycloalkoxy group represented by X is usually one having a carbon, number of from 3 to 10, and a monocyclic group such as cyclopropyl, cyclobutyl, cyclopentyl, cyciohexyl or cyclooctyl, as well as a condensation type polycyclic group, may, for example, be mentioned. However, preferred is a monocyclic group. The secondary %

substituent of the substitutable cycloalkoxy group may, :

for example, be a halogen, an alkyl, an alkoxy or hydroxyl.. Of these substitutable cycloalkoxy groups, most preferred is a cyclohexyloxy group.

The hydrocarbon moiety in the substitutablehydrocarbon group represented by X may, for example, be a Ci~₆ alkyl group (such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl or t-butyl), a C₂_₆ alkenyl (such as vinyl, allyl, xsopropenyl or 3-methyl--2butenyl) .. a C₂.₆ alkynyl (such as ethynyl, 1-propynyl or 2~propynyi), a C₃_₆ cycloalkyl (such as cyclopropyl, ft·»¹ cyclopentyl or cyclohexyl), or a C₅_₁₀ aryl. Further, the secondary substituent of the substitutable hydrocarbon group may be from one to five substituents which are the same or different, selected from the group consisting of an aryl, an aryloxy, hydroxyl, nitro, nitroxy, a halogen (such as fluorine, chlorine, bromine or iodine), a haloalkoxy (such as a Ci_₄ haloalkoxy such as CF₃O or HCF2O) , a cycloalkyl, amino, an alkylthio and cyano. Of these substitutable hydrocarbon groups, preferred is a substitutable alkyl group, and particularly preferred is an alkyl group. Further, a C1-4 alkyl group is most preferred among alkyl groups.

The alkylthio moiety in the substitutable alkylthio group represented by X may, for example, be a Ο_χ_6 alkylthio (such as methylthio, ethylthio, propylthio, isopropylthio, butylthio, isobutylthio or t-butylthio), and preferably a Ci_₄ alkylthio (such as methyl thio or ethyl thio) may, for example, be mentioned. Of these alkylthio groups which may be substituted, preferred is an alkylthio group, particularly preferred is a C1-4 alkylthio group. The secondary substituent of the substitutable alkylthio group may be from one to five substituents which are the same or different, selected from the group consisting of an aryl, an aryloxy, hydroxyl, nitro, nitroxy, a halogen (such as fluorine, chlorine, bromine or iodine), a haloalkoxy (such as a C1-4 haloalkoxy such as CF3O or HCF₂O) and cyano.

(K7

CM

O

The carboxyl group which may be esterified or ami dated, represented by X, may, for example, be a carboxyl group which may be esterified such as a Ci-_f>aIkoxycarbonyl group (such as a methoxycarhonyl group, an ethoxycarbonyl group, a propoxycarbonyl group, an isopropoxycarbonyl group, a butoxycarbonyl group, an isobutoxycarbonyl group or t-butoxycarbonyl group), a nitroxy C1-4 alkoxyaminocarbonyl group (such as 2~ nitroxyethoxycarbonyl group or a 3-nitroxypropoxycarbonyl

W^:’ ':

group) , a phenyl Cl./, alkoxycarbonyl group (such as a tgif benzyloxycarbonyl group or a phenethyIoxycarbonyl group);

’f ·.

or a carboxyl group which may be amidated such as a carbamoyl group, a C^g monoalkylaminocarbonyl group (such as a methylaminocarbonyl group, an ethylaminocarbonylgroup, a propylaminocarbonyl group, an . isopropylaminocarbonyl group, a butylaminocarbonyl group, an isobutylaminocarbonyl group or a t-butylaminoc.arbonyl group), a Ci_₆ dialkylaminocarbonyl group (such as a dimethylaminocarbonyl group, a diethylaminocarbonyl group, a dipropylaminocarbonyi group, a diisopropylaminocarbonyl group, a dibutylaminocarbonyl group or an isobutylaminocarbonyl group) , a nitroxy ¢1..4 alkylaminocarbonyl group (such as a 2nitroxyethylaminocarbonyl group or a 3nitroxypropylaminocarbonyl group) , a phenyl C1-4 alkylaminocarbonyl group (such as a benzylaminocarbonyl group or a phene thy laminocarbonyl group) , a C3~_b10 cycloalkylaminocarbonyl group (such as a cyclopropylaminocarbonyl group, a cyclopentylaminocarbonyl group or a cyclohexylaminocarbonyl group), a cyclic aminocarbonyl group (such as a morpholinocarbonyl group, a piperidinocarbonyl group, a pyrrolidinocarbonyl group or a thiomorpholinocarbonyl group) or an aminocarbonyl group.

The substitutable amino group represented by X may, for example, be an amino group or an alkylamino group such as a monoalkylamino group or a dialkylaraino group. The alkyl moiety in the alkylamino group (a monoalkylamino group or a dialkylamino group) is preferably a C1-4 alkyl. The secondary substituent of the substitutable amino group may be from one to five substituents which are the same or different, selected from the group consisting of an aryl, an aryloxy, hydroxyl, nitro, nitroxy, a halogen (such as fluorine, chlorine, bromine or iodine) , a haloalkoxy (such as a C1-4 haloalkoxy group such as CF₃O or HCF₂O) , a cycloaikyi, amino, an alkylthio and cyano.

The alkyl moiety in the substitutable alkyl group represented by each of R¹ and R² is preferably a Ci_6 alkyl (such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl or t-butyl) , and among them, preferred is a C_x_4 alkyl. The secondary substituent of the substitutable alkyl group may be from one to five substituents which

CM o

Cm

G t25 are the same or different, selected from the group consisting of an aryl, an aryloxy, hydroxyl, nitro, nitroxy, a halogen (such as fluorine, chlorine, bromine or iodine) , a haloalkoxy (such as a Ci_₄ haloalkoxy such, as CF₃O or HCF₂O) , a cycloalkyl, amino, an alkylthio and cyano. Of these substitutable alkyl groups, preferred is an alkyl group which is not substituted, and particularly preferred is a C^..^ alkyl group. Among them, most preferred is a methyl group.

The alkoxy moiety in the substitutable alkoxy group represented by R² is preferably a Ci-β (alkoxy such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy or t-butoxy) , and among them, preferred is a Ci..a alkoxy. The secondary substituent of the substitutable alkoxy group may be from one to five substituents which are the same or different, selected from the group consisting of an aryl group, an aryloxy group, a hydroxyl group, a nitro group, a nitroxy group, a halogen atom (such as fluorine, chlorine, bromine or iodine), a haloalkoxy group {such as a Ci_₄ haloalkoxy group such as CF₃O or HCF2O), a cycloalkyl group, an amino group, an alkylthio group and a cyano group. Of these substitutable alkoxy groups, most preferred is an alkoxy group which is riot substituted.

As the aryl moiety in the substitutable aryloxy group represented by Ph, a condensation type polycyclic group such as naphthyl, as well as phenyl, may be

18»

PM

I i

mentioned, and preferred is phenyl. The secondary substituent of the substitutable aryloxy group may, for example, be a halogen atom, an alkyl group, an alkoxy group or a hydroxyl group. Of these substitutable aryloxy groups, most preferred is a phenoxy group which is not substituted.

The cycloalkyl moiety in the substitutable cycloalkoxy group represented by R² is usually one having a carbon number of from 3 to 10, and a monocyclic group such as cyclopropyl, cyclobutyl, cyclopentyi, cyclohexyl or cyclooctyl, as well as a condensation type polycyclic group, may, for example, be mentioned, however, preferred is a monocyclic group. The secondary substituent of the substitutable cycloalkoxy group may, for example, be a halogen, an alkyl, an alkoxy or hydroxyl. Of these substitutable cycloalkoxy groups, most preferred is a cyclohexyloxy group which is not substituted.

Here, the aryl moiety, the cycloalkyl group and the alkylthio group in the secondary substituent of the substituent represented by X, R¹ and R² are as defined for the substituents represented by X, R¹, R² and R³.

The compound represented by the formula (I) may form a salt together with an acid substance, and it can form, for example, an inorganic salt such as a hydrochloride, a hydrobrornate, a phosphate, a sulfate or a nitrate, or an organic salt such as an acetate, a benzoate, a ptoluenesulfonate, a methanesulfonate or a ,K5 «»

CM

propanesulfonate.

BEST MODE FOR CARRYING OUT THE INVENTION

Some of the preferred modes of the benzoylpyridine derivative represented by the formula (I) are shown below. These modes may be mutually combined. Further, these compounds are useful as a fungicide.

R³', R³” and R²' ' are as defined for the above R², and X¹, X², X³ and X⁴ are as defined for the above X.

(1) A benzoylpyridine derivative represented by the

wherein X, n and R¹ are as defined in the above general formula (I), R²' is a substitutable alkyl group,, a substitutable alkoxy group, a substitutable aryloxy group, a substitutable cycloalkoxy group or a hydroxyl group, p is 1, 2 or 3. and R₂ is a substitutable alkoxy group or a hydroxyl group, provided that at least, two of R·⁴’ and P/'' may contain an oxygen atom to form a condensed ring (excluding a case where the pyridine ring is substituted by a benzoyl group at the 2-position; the pyridine ring is substituted by an alkoxy group, a hydroxyl group or a benzyloxy group at the 3-position; and n is 1, p is 1).

(2) The benzoylpyridine derivative or its salt fo id (lo ©

I i

<

,ο ft according to the above item (1), which is represented by the formula (I''):

wherein X is a halogen atom, a nitro group, a substitutable alkoxy group, a substitutable aryloxy group, a substitutable cycloalkoxy group, a substitutable hydrocarbon group, a substitutable alkylthio group, a cyano group, a carboxyl group which may be esterified or amidated, or a substitutable amino group; n is 1, 2 ,3 or 4; R¹ is an alkyl group; R²' is a substitutable alkyl group, a substitutable alkoxy group, a substitutable aryloxy group or a substitutable cycloalkoxy group; p is 1, 2 or 3; and each of R²” and R²’ is a substitutable alkoxy group.

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

(4) The benzoylpyridine derivative or its salt according to the above item (3), which is represented by the formula (1''):

as ,1

Ν' (X)n-1 /\ \ /^_R2 r²“' wherein X is a halogen atom, a nitro group, a substitutable alkoxy group, a substitutable cycloalkoxy group, an alkyl group, a substitutable alkylthio group or a substitutable amino group; n is 1, 2, 3, or 4,; R~ is an aikvl group; R²’ is a substitutable alkyl group, a substitutable alkoxy group, a substitutable aryloxy group or a substitutable cycloalkoxy group; p is 1, 2 or 3; each of R‘^! and R²' is a substitutable alkoxy group (excluding a case where the pyridine ring is substituted by a benzoyl group at the 3-position, and the pyridine ring has a CF₃ group at at least one of the 2,6-posiLions).

(5) The benzoylpyridine derivative or its salt according to the above item (1), which is represented by the formula (I''')

Ai

wherein .X is a halogen group, an alkyl group.

atom, a substitutable alkoxy a CF₃ group or an alkylthio group, •u ,

Wu «5»

I fe fc fc Κ n is 1, 2, 3 or 4; R¹ is an alkyl group; R² is a substitutable alkyl group, a substitutable alkoxy group or a substitutable cycloalkoxy group; p is 1, 2 or 3; and each of R² and R² is a substitutable alkoxy group.

(6) The benzoylpyridine derivative or its salt according to the above item (5), which is represented by

a® «Μ

CM o

wherein X is a halogen atom, a substitutable alkoxy group, an alkyl group, a CF₃ group or an alkylthio group; n is 1, 2, 3, or 4; R¹ is an alkyl group; R²' is a substitutable alkyl group, a substitutable aryloxy group or a substitutable cycloalkoxy group; p is 1, 2 or 3; each of R² and R²' is a substitutable alkoxy group (excluding a case where the pyridine ring is substituted by a benzoyl group at the 3-position, and the pyridine ring has a CF₃ group at at least one of the 2,6positions).

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

(8) The benzoylpyridine derivative or its salt

SC Τ

ΙΟ according to the above item (5) or (6), wherein n is 3 or

4.

(S) The benzoylpyridine derivative or its salt according to the above item (5) or (6), wherein, in a case where n is 1 or 2, the halogen atom represented by X is a fluorine atom or a chlorine atom.

(10) The benzoylpyridine derivative or its salt according to the above item (5), which is represented by the formula (I’' ’ ') ;

S,.

V

CO

V, '**,« wherein X is a halogen atom, an alkoxy group, an alkyl group, a CF₃ group or an alkylthio group,- n is 1, 2 or 3; R¹ is an alkyl group.: R²' is an alkoxy group; p is 1, 2 or 3; and each of R²' and. R²' is an alkoxy group.

(11) The benzoylpyridine derivative or its salt according to the above item (10), which is represented by

wherein X is a halogen atom, an alkoxy group, an alkyl group, a CF₃ group or an alkylthio group; n is 1, 2 or 3; R¹ is an alkyl group; R²’ is an alkoxy group; p is 1, 2 or 3; and each of R²” and R²*” is an alkoxy group (excluding a case where the pyridine ring is substituted by a 5 benzoyl group at the 3-position, and the pyridine ring has a CF₃ group at at least one of the 2,6-positions).

(12) The benzoylpyridine derivative or its salt according to the above item (8), which is represented

wherein B is -CX⁴= when A is -N=; B is -N= when A is -CH=; each of X¹ and X² which are independent of each other, is a halogen atom, an alkoxy group, an alkyl group, a CF₃ group or an alkylthio group; X³ is a hydrogen atom, a halogen atom, an alkoxy group, an alkyl group, a CF₃ group or an alkylthio group; X⁴ is a hydrogen atom, a halogen atom, an alkoxy group, an alkyl group, a CF₃ group or an alkylthio group; R¹ is an alkyl group; R²' is an alkoxy group; p is 1, 2 or 3; and each of R²” and R²'” is an alkoxy group.

(13) The benzoylpyridine derivative or its salt according to the above item (8), which is represented by

wherein B is -CX⁴= when A is -N=; B is -N= when A is ~CK=; each of X³ and which are independent of each other, is a halogen atom, an alkoxy group, an alkyl group, a CF3 group or an alkylthio group; X³ is a hydrogen, atom, a halogen atom, an alkoxy group, an alkyl group, a CF3 group or an alkylthio group; X⁴ is a hydrogen atom, a halogen atom, an alkoxy group, an alkyl group, a CF₃ group or an alkylthio group; R¹ is an alkyl group; R⁴' is an alkoxy group; p is 1, 2 or 3; and each of R‘ and R²' is an alkoxy group (excluding a case where A is -CH= and 33 is -N=, and X² is a CF3 group) ,

The compound represented by the formula (I) or its salt may be produced in accordance with a known production process of an analogous compound (such as a process as disclosed in WO96/17829). However, as the preferred modes, Processes 1 to 3 as shown in the following schemes may be mentioned. Here, X, R¹, R ² , n and in in the formulae are as defined above. One of the substituents represented by M¹ in the formula (II) and M²in the formula (III) is a cyano group, and the other is a β» '

tfh *

<

metal atom or a composite salt thereof; the substituent represented by W in the formula (V) is a halogen atom or a trifluoromethane sulfonyloxy group; one of the substituents represented by M³ in the formula (VI) and M⁴ in the formula (VII) is a formyl group, and the other is a metal atom or a composite salt thereof.

Process 1

A process for producing the compound represented by the formula (I), which comprises subjecting a compound represented by the formula (II) and a compound presented by the formula (ΙΠ) to a condensation reaction ^Jro produce an imine compound represented by the formula io (VIII):

wherein X, R¹, R², n and m are as defined above, and Z is a metal atom or a composite salt thereof, and hydrolyzing

1_C

The metal atom represented by each of M¹ and M* in the formulae (II) and (III) may, for example, be a typical metal atom such as lithium, magnesium, zinc or copper; or a transition metal atom such as palladium or ruthenium. Further, a composite salt of a metal atom may be used instead of a metal atom.

The compound of the formula (II) wherein M¹ is a cyano group and the compound of the formula (III) wherein is a cyano group may be produced in accordance with a known process such as a process as disclosed in Journal of the Chemical Society, Perkin transactions 1 pages

AS» ^,;!Ή„

i._s ^;,i<.

*.

2323-2326, 1999.

The condensation reaction to produce an imine compound is carried out in the presence of a proper solvent {such as an inert solvent such as tetrahydrofuran, diethyl ether, dimethoxyethane, hexane, benzene, toluene or methylene chloride, or a mixed

c* solvent thereof) at a reaction temperature of from -100 to 70°C, preferably from -80 to 30°C. This reaction is carried out preferably in an inert gas atmosphere of e.g nitrogen or argon.

The imine compound produced by the condensation reaction is hydrolyzed by a known procedure and converted into the compound represented by the formula (I) . The hydrolysis reaction may be carried out in the presence of e.g. water, an alcohol or a mixture thereof. Here, in Process 1, the condensation reaction and the hydrolysis reaction are usually carried out continuously, and no imine compound is isolated. Further, to obtain the compound represented by the formula (I) with a high yield, it is preferred to carry out the hydrolysis reaction after the condensation reaction is completely conducted.

Process 2

CM o

A process for producing the compound represented by the formula (I), which comprises subjecting a compound represented by the formula (IV) and a compound represented by the formula (V) to a condensation reaction to produce a compound represented by the formula (IX):

wherein X, R¹, R\ n and m are as defined above, and subjecting it to decyanogenation oxidatively in the presence of a base,

The reaction to produce the compound represented by the formula (IX.) at the first half stage of Process 2 is carried out usually in the presence of a base preferably in a solvent. The base to be used for the reaction, may, for example, be lithium hydride, sodium hydride, sodium methoxide, sodium ethoxide or potassium tert-butoxide.

The solvent may, for example, be tetrahydrofuran, diethyl ether, benzene, toluene, methylene chloride, chloroform or DMF, or a mixed solvent thereof. This reaction, is carried out preferably at a reaction temperature of from 0 to 100°C. Further, it is carried out preferably in. an inert gas atmosphere of e.g. nitrogen or argon. Further, sodium benzenesulfirate or sodium p-toluenesulfinate maybe added as the case requires to accelerate the reaction.

The oxidative decyanogenation reaction at the last half stage in Process 2 is carried out in the presence of a base. The base may, for example, be sodium hydride, potassium, hydride, sodium carbonate or potassium carbonate. Further, a phase-transfer catalyst (such as benzyl tr-iethylammonium chloride or tetrabutylammonium hydrogensulfate) may be used as the case requires . This reaction is usually carried out in a proper solvent (such as an inert solvent such as methylene chloride, chloroform, 1,2-dichloroethane, benzene, toluene, DMF or fe ’CSV gvi est

-·

DMSO, or a water-containing solvent or a mixed solvent thereof) at a reaction temperature of from 0 to 50°C.

Process 3

A process for producing the compound represented by 5 the formula (I) , which comprises reacting a compound represented by the formula (VI) and a compound represented by the formula (VII) to produce phenylpyridyl methanol represented by the formula (X):

(wherein X, n, m, R¹ and R² are as defined above with a proviso as in formula (I)) and oxidizing it.

Each of metal atoms represented by M³ and M⁴ in Process 3, may, for example, be a typical metal atom such as lithium, magnesium, zinc or copper; or a transition metal atom such as palladium or ruthenium. Further, a composite salt of a metal atom may be used instead of a metal atom.

The compound of the formula (VI) wherein the substituent represented by M³ is a formyl group and the compound of the formula (VII) wherein the substituent represented by M⁴ is a formyl group, may usually be produced in accordance with a known process such as a

process as disclosed in Journal of Organic Chemistry vol. 57., pages 6847-6852, 1992.

The phenylpyridyl methanol represented by the formula (X), formed from the compound represented by the formula (VI) and the compound represented by the formula (VII), may be oxidized by a known means such as a metal •oxidising agent such as manganese dioxide or chromic acid, a Swern oxidation method (dimethylsulfoxide + oxalyl chloride) oi a ruthenium oxidation method (tetrapropylammonium perruthenate + N-methylmorpholine-Noxide) and converted to a compound .represented by the formula (I)

Now, mode of carrying out Process 3 is described below, (1) A process fox producing the compound represented by the formula (I) , which comprises reacting a substituted benzaldehyde represented by the formula (VI1) :

HC

(wherein R¹, R² and in are as defined above) , and a. metal salt of a substituted pyridine derivative represented by the formula (V1I-1):

(wherein X is as defined above, and Z is a metal atom or a composite salt thereof), to produce phenylpyridyl methanol represented by the formula (X), and oxidizing it.

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

R¹

‘(R²)m (wherein R¹, R² and m are as defined above, and Z is a metal atom or a composite salt thereof), and a substituted pyridylaldehyde represented by the formula (VII-2) :

it Λ

N (wherein X is as defined above), to produce phenylpyridyl 25 methanol represented by the formula (X), and oxidizing it.

Here, the preferred modes of the phenylpyridyl

Ski gj

CM o

methane! represented by the formula ( X) which is an intermediate for production of the compound represented by the formula (I) are shown below.

(1) Phenylpyridyi methanol represented by the

wherein X, n and R¹ are as defined for the above general formula (I) , R²' is a substitutable alkyl group, a substitutable alkoxy group, a substitutable aryloxy group, a substitutable cycloalkoxy group or a hydroxyl group, p is 1, 2 or 3; and R²’* is a substitutable alkoxy group or a hydroxyl group, provided that at least two of R²' and R^2-' may contain an oxygen atom to form a condensed ring (excluding a case where the pyridine ring is substituted by a benzoyl group at the 2-position; the pyridine ring is substituted by an alkoxy group, a hydroxyl group or a bensyloxy group at the 3-position; and n is 1, p is 1).

(2) The phenylpyridyi methanol according to the above item (1), which is represented by the formula.

Λ , ijgjB t:

«· ’ a, &

<·;

(X' ·) ;

wherein X is a halogen atom, a nitro group, a substitutable alkoxy group, a substitutable aryloxy group, a substitutable cycloalkoxy group, a substitutable hydrocarbon group, a substitutable alkylthio group, a cyano group, a carboxyl group which may be esterified or amidated, or a substitutable amino group; n is 1, 2, 3 or 4; R¹ is an alkyl group; R²’ is a substitutable alkyl group, a substitutable alkoxy group, a substitutable aryloxy group or a substitutable cycloalkoxy group, p is 1, 2 or 3, and each of R²” and R²'” is a substitutable alkoxy group.

(3) The phenylpyridyl methanol according to the above item (2), wherein X is a halogen atom, a nitro group, a substitutable alkoxy group, a substitutable cycloalkoxy group, an alkyl group, a substitutable alkylthio group or a substitutable amino group.

(4) The phenylpyridyl methanol according to the above item (2) or (3), wherein the pyridine ring is substituted by a benzoyl group at the 4-position.

(5) The phenylpyridyl methanol according to the above item (1), which is represented by the formula

CM ©

wherein X is a halogen atom, a substitutable alkoxy group, an alkyl group, a CF₃ group or an alkylthio group; n is 1, 2, 3 or 4; R¹ is an alkyl group; R²’ is s. substitutable alkyl group, a substitutable alkoxy group or a substitutable cycloalkoxy group; p is 1, 2 or 3; and each of and R²' ’ is a substitutable alkoxy group.

(6) The phenylpyridyl methanol according to the above item (5), which is represented by the formula (X’ 7 :

€ • V UV

CM '

c<

I *

wherein X is a halogen atom, an alkoxy group, an alkyl group, a CF₃ group or an alkylthio group; n is 1, 2 or 3; R^j is an alkyl group; R²' is an alkoxy group; p is 1, 2 or

3; and each of R²' and R⁴’’’ is an alkoxy group.

(7) The phenylpyridyl methanol according to the above icem (5) or (6), wherein the pyridine ring is substituted by a benzoyl group at the 4-position.

(8) The phenylpyridyl methanol according to the above item (6), which is represented by the formula (X ') :

wherein B is -CX⁴= when A is -N=; B is -N= when A is -CH=; each of X¹ and X² which are independent of each other, is a halogen atom, an alkoxy group, an alkyl group, a CF3 group or an alkylthio group; X³ is a hydrogen atom, a halogen atom, an alkoxy group, an alkyl group, a CF3 group or an alkylthio group; X⁴ is a hydrogen atom, a halogen atom, an alkoxy group, an alkyl group, a CF₃ group or an alkylthio group; R¹ is an alkyl group; R²' is an alkoxy group; p is 1, 2 or 3; and each of R²” and R²’ is an alkoxy group.

(9) The phenylpyridyl methanol according to the above item (8), wherein A is -N=.

A substituent may further be introduced into the compound represented by the formula (I) electrophilically or nucleophilically. That is, the compound represented by the formula (I) may be converted into a compound

CM

represented by the formula (I-a) or (I-b) as illustrated in the following scheme. Further, it is also possible to radically introduce a substituent into the compound represented by the formula (X) . Here, in the formula (Ia) , E is an electrophilic reagent, and in the formula (Ίb't , Nu is a nucleophilic reagent.

n' and n'' are as defined for the above n.

io

The reaction to prepare the compound represented by the formula (I-a) varies properly depending upon the electrophile, and the reaction may usually be carried out by a known process or a. process in accordance therewith. For example, the above-described Process 1 may be

V I lift.

employed. The nucleophilic substitution to prepare the compound represented by the formula (I-b) varies properly depending upon the nucleophile, and the reaction may usually be carried out by a known process or a process in accordance therewith. For example, in a case of an ethyloxy nucleophilic reagent, it is preferred to carry out the reaction in the presence of an inert solvent such as ethanol or dioxane, toluene or octane as the solvent, at a reaction temperature of from 0 to 120°C for a proper time. The ethyloxy nucleophilic reagent is used in from 0.1 to 10 mol equivalent amount, preferably in from 0.5 to 5 mol equivalent amount.

Further, the compound represented by the formula (Ιο) (the compound of the formula (I) wherein X is a halogen atom) may further be converted into a compound represented by the formula (I-d) by removing the halogen substituent, as shown in the following scheme. For the reaction as illustrated by the scheme, catalytic hydrogenation, hydrogen transfer reaction or metal reduction reaction may properly be employed. In the scheme, Hal is a halogen atom.

«Μ

The catalytic hydrogenation may be carried out in the presence of a catalyst under hydrogen gas atmosphere under· normal pressure or under elevated pressure in the presence cf a proper solvent. The catalyst to be used may, for example, be a catalyst system having platinum, palladium, rhodium, ruthenium, nickel or iridium. The solvent to be used may, for example, be water, an alcohol (such as methanol or ethanol), ethyl acetate, acetic acid, dioxane, ether, benzene or hexane. In such a case, the catalyst is used in a proportion of from 0.01 to 1.2 mol based on the compound represented by the formula (I- iiP

c) . Further, the reaction may be carried out in the :

presence of a base such as triethylamine or sodium -p.

-'tip,...

hydrogen carbonate. Further, a known reduction reaction ¢0 may be employed such as hydrogen transfer reaction (e.g. Λ 15 palladium carbon, ammonium formate as a hydrogen source, or sodium dihydrogen phosphate) or a metal reduction reaction (e.g. samarium diiodide).

Sow, specific Synthesis Examples of the benzoylpyridine derivative represented by the formula (I) and the Intermediate for its production are described below (tne compounds In Synthesis Examples are based on ICJPAC nomenclature, and the substitution posit ions may be different from those shown in Tables as mentioned hereinafter, expediently).

SYNTHESIS EXAMPLE 1

Synthesis of 3-(2,3,1-trimethoxy-6-methylbenzoyl) -2 ,_6dichloro-4-trifluoromethylpyridine (compound No, 3)

2'_t & >

(a) 14 mfi (20 mmol) of n-butyllithium (1.5 M hexane solution) was dropwise added at 0°C to a solution having 2.9 mfl (21 mmol) of diisopropylamine dissolved in 62 mfi of tetrahydrofuran, followed by stirring for 30 minutes.

The solution was cooled to -20°C, a solution having 4.0 g (19 mmol) of 2,6-dichloro-4-trifluoromethylpyridine dissolved in 5 mfi of tetrahydrofuran was added thereto, followed by stirring for 5 minutes, and a solution having

3.8 g (18 mmol) of 2,3,4-trimethoxy-6-methylbenzaldehyde dissolved in 7 mfl of tetrahydrofuran was added thereto, followed by stirring for 1.5 hours. 3 0 mfi of water was added to the mixture to terminate the reaction, and tetrahydrofuran was distilled off under reduced pressure. Extraction with ethyl acetate was carried out, the organic layer was dried over anhydrous sodium sulfate and subjected to filtration, and the solvent was distilled off under reduced pressure. The crude product thus obtained was purified by silica gel column chromatography to obtain 6.2 g (yield 81%) of (2,3,4-trimethoxy-620 methylphenyl)(2,6-dichloro-4-trifluoromethyl-3pyridyl)methanol (brown oily substance).· (b) 14 g of manganese dioxide was added to a solution having 5.4 g of (2,3,4-trimethoxy-6methylphenyl)(2,6-dichloro-4-trifluoromethyl-325 pyridyl)methanol obtained in step (a) dissolved in 140 mfl of toluene, followed by stirring under reflux by heating for 6 hours. The mixture was cooled and then subjected

CO

CM

Co

O to filtration, and toluene was distilled off under reduced pressure to obtain 4.4 g (yield 81%) or. 3-(2,3,4tximethoxy-6-methyl benzoyl)-2,6-dichloro-4trifluoromethylpyridine (compound No. 3; m.p. 8.1-83°C) .

SYNTHESIS EXAMPLE 2

Synthesis of 3- (2,3,4-trimethoxy-6-methylbenzoyl) --2chioro-4-trifluoromethylpyridine (compound No. llj and 3(2,3,4-trimethoxy-6-methylbenzoyl)-4trifluoromethylpyrldine (compound No. 7)

2.4 mfl (17 mmol) of triethylamine and 0.3 g of 5% palladium carbon were added to a solution having 3.4 g (8.0 mmol) of 3 -(2,3,4-trimethoxy-6-methylbenzoyl)-2,6dichloro-4-trifluoromethylpyridine (compound No. 3) obtained in Synthesis Example 1 dissolved .in 50 xn6 of methanol, followed by stirring under hydrogen atmosphere for 6.5 hours. The mixture was subjected to filtration, 50 τ»β of water was added thereto, and methanol was distilled off under reduced pressure. Extraction of ethyl acetate was carried out, the organic layer was dried over anhydrous sodium sulfate and subjected to filtration, and the solvent was distilled off under reduced pressure. The crude product thus obtained was purified by silica gel column chromatography to obtain 1.7 g (yield 55%) of 3- (2,3,4-trimethoxy-6methylbenzoyl)-2-chloro-4-trifluoromethylpyridine (compound No. 11; m.p. 110~112°C) and 1.1 g (yield. 37%) of 3-(2,3,4-trimethoxy-6-methylbenzoyl) -42 5 trifluoromethylpyridine (compound No. 7; m.p. 59-62°C).

SYNTHESIS EXAMPLE 3

Synthesis of 4-(2,3,4-trimethoxy-6-methylbenzoyl)-2,5dichloro-3-trif luoromethylpyridine (compound No. 90) (a) 17 τα& (25 mmol) of n-butyllithium (1.5 M hexane solution) was dropwise added at 0°C to a solution having 3.6 mfi (25 mmol) of di isopropylamine dissolved in 60 mfi of diethyl ether, followed by stirring for 45 minutes.

The solution was cooled to -78°C, a solution having 6.0 g (24 mmol) of 2,3,6-trichloro-5-trifluoromethylpyridine dissolved in 8 ιηβ of diethyl ether was added thereto, followed by stirring for 5 minutes, and a solution having 5.0 g (24 mmol) of 2,3,4-trimethoxy-6-methylbenzaldehyde dissolved in 12 mfi of toluene was added thereto, followed by stirring for 1 hours. 30 mfi of water was added to the mixture to terminate the reaction, the aqueous layer was extracted with ethyl acetate, and then the organic layer was dried over anhydrous sodium sulfate and subjected to filtration, and the solvent was distilled off under reduced pressure to obtain (2,3,4-trimethoxy-6methylphenyl)(2,3,6-trichloro-5-trifluoromethyl-4pyridyl)methanol (m.p. 131-135°C).

(b) 2.7 mfi (19 mmol) of triethylamine and 0.9 g of 5% palladium carbon were added to a solution having (2,3,4trimethoxy-6-methylphenyl)(2,3,6-trichloro-5trifluoromethyl-4-pyridyl)methanol obtained in step (a) dissolved in 200 mfi of methanol, followed by stirring

Ki

16. A vaccine formulation according to any preceding claim wherein the mutant Leishmania is a drug resistant marker-free mutant.

17. A vaccine formulation according to any preceding claim tor eliciting at least a cellular immune response

18. A vaccine formulation according to claim 17 wherein the cellular immune response is a Thl cell response.

A vaccine formulation according to any preceding claim further comprising an adjuvant and/or cy tokine.

20. A vaccine formulation according to any preceding claim further comprising at least one disfunctional cysteine proteinase, wherein said disfunctional cysteine proteinase is substantially enzymatically inactive, but which is antigenic or immunogenic. did <3

21. A substance or composition for use in a method of vaccinating against Leishmania, said substance or composition comprising a vaccine formulation according to any one of claims 3 - 20, and said method comprising administering to an animal an effective, non-toxic amount of said substance or composition.

A substance or composition for use in a method of treatment according to claim 21 wherein the method comprises parenteral administration.

23. A substance or composition for use in a method for the prophylaxis and/or treatment of Leishmaniasis, said substance or composition comprising a mutant Leishmania wherein the mutant comprises at least one defective cysteine proteinase gene type, such that the mutant Leishmania is substantially incapable of expressing a functionally active form of said at least one cysteine proteinase, and said method comprising administering said substance or composition.

24. A pharmaceutical formulation comprising a vaccine according to any one of claims 3-20 together with a carrier or excipient.

solution having 1.5 g (4.2 mmol) of 3-(4,5-dimethoxy-2methylbenzoyl)-2-chloro-4-trifluoromethylpyridine synthesized in accordance with a process in Synthesis Example 1 dissolved in 20 mfl of toluene, followed by stirring under reflux by heating for 4 hours. The mixture was cooled, and then 20 mfl of water was added thereto to terminate the reaction, the aqueous solution was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and subjected to filtration by using a silica gel cake. The solvent was distilled off under reduced pressure to obtain 1.5 g (yield 99%) of 3-(4,5-dimethoxy-2-methylbenzoyl)-2methoxy-4-trifluoromethylpyridine (compound No. 32; m.p. 125-127°C).

SYNTHESIS EXAMPLE 5

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

CM

O*

CM

(a) 3.2 mfl (62 mmol) of bromine was dropwise added at 0°C to a solution having 7.0 mfl (58 mmol) of 3,420 (methylenedioxy) toluene and 5.5 mfl (68 mmol) of pyridine dissolved in 110 mfl of di chloromethane, 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 sodium hydroxide solution, dried over anhydrous sodium sulfate and subjected to filtration, and the solvent was distilled off under reduced pressure. The crude product thus

SB obtained was purified by silica gel column chromatography to obtain 13 g (yield 39%) of 2-bromo-4,5(methylenedioxy) toluene .

(b) 13 mfi (20 mmol) of n-butyllithium (1.5 M hexane 5 solution) was dropwise added at -78°C to a solution having 4.0 g (19 mmol) of 2-bromo-4,5(methylenedioxy)toluene dissolved in 50 mfi of tetrahydrofuran, followed by stirring for 30 minutes, and 1., S mfi (19 mmol) of dimethyl formamide was added thereto, followed by stirring for 7 0 minutes. 30 mfl of water was added to the mixture to terminate the reaction, and yy tetrahydrofuran was distilled off under reduced pressure. Extraction with chloroform was carried out, the: organic layer was dried over anhydrous sodium sulfate and

O subjected to filtration by using a silica gel cake, and ii the solvent was distilled off under reduced pressure to obtain 3.1 g (yield 99%) of 2-methyl-4,5(methylenedioxy)benzaldehyde (m.p. 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-methyl4,5-(methylenedioxy)benzaldehyde, 2.1 g (yield 73%) of (2-methyl-4,5-(methylenedioxy) phenyl)(2-chloro-itritluoromethyl-3-pyridyl)methanol (m.p. 127-130^aC) was obtained by a process in accordance with step (a) of

Synthesis Example 1.

id) Using 1.5 g {4.3 mmol) of (2-methyl-4,5(me thy 1 en edi oxy) phenyl) (2 - chi or o - 4 -1 r i f luorome t hy i -- 3 37 pyridyl)methanol obtained in step (c) and 8.0 g (92 mmol) of manganese dioxide, 0.3 g (yield 22%) of 3-(4,5(methylenedioxy)-2-methylbenzoyl]-2-chloro-4trifluoromethylpyridine (compound No. 13; m.p. 119-122°C) was obtained by a process in accordance with step (b) of Synthesis Example 1.

SYNTHESIS EXAMPLE 6

Synthesis of 3-(5-benzyloxy-4-methoxy-2-methylbenzoyl)-2chloro-4-trifluoromethylpyridine (compound No. 27) io (a) A dimethylformamide (15 mfi) solution of 2methoxy-4-methylphenol (6.91 g) was dropwise added to a dimethylformamide (20 mfi) suspension of sodium hydride (2.4 g) under cooling with ice, followed by stirring for 3 0 minutes. A dimethylformamide (15 mfi) solution of benzyl bromide (9.41 g) was dropwise added thereto, and tetrabutylammonium bromide in a catalytic amount was added thereto, followed by stirring at the same temperature for 30 minutes. The temperature was raised to room temperature and stirring was further carried out for one night. The reaction solution was poured into water (250 mfi), and extraction with ethyl acetate (100 mfi) was carried out three times. The ethyl acetate phase was washed with water (100 mfi) three times and then washed with an aqueous sodium chloride solution (100 mfi) .

After drying over magnesium sulfate, the solvent was distilled off under reduced pressure, the residue was purified by silica gel column chromatography (hexane-

CM

c.

<

ethyl acetate) to obtain 11.4 g of 4-benzyloxy-· 3 ~ methoxytoluene (m.p, 38-39°C) quantitatively, and its structure was confirmed by nuclear magnetic resonance spectrum..

(bi 4-benzyloxy-3-methoxytoluene (8.0 g) was dissolved in dimethylformamide (30 mfi) , and a dimethylformamide (.15 mfi) solution of N-bromosuccinimide (6,36 g) was dropwise added thereto, followed by stirring at room temperature fox· one night. The reaction solution io was poured into ice water (400 mfi) , and crystals thus deposited were collected by filtration, adequately washed with water, and dried for one night to obtain 10.64 g of

4. - benz.y i oxy - 2 -bromo 5 -methoxyt o luene (m.p. 110--311 ° C) substantially quantitatively, and its structure was confirmed by nuclear magnetic resonance spectrum.

(c) A hexane solution (17 mfl) of n-butyllithium was dropwise added to a tetrahydrofuran (190 mfl) solution of 4-benzyloxy-2-bromo-5-methoxytoluene (7.83 g) at -78°C over a period of 20 minutes, followed by stirring at the same temperature for .1 hour. A tetrahydrofuran (30 mfl) solution of dimethylformamide (3.73 g) was dropwise added thereto at -78°C, followed by stirring at the same temperature for 1 hour. The temperature was gradually raised to room temperature, and stirring was further carried out for one night. The reaction solution was poured into an aqueous ammonium chloride solution. (2C0 mfl), and extraction with ethyl acetate (150 mfl) was >g

CM .»· ί β s

c.

carried out twice. The ethyl acetate phase was washed with an aqueous sodium chloride solution (100 mfi) twice and dried over magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexaneethyl acetate) to obtain 3.14 g (yield 48%) of 5benzyloxy-4-methoxy-2-methylbenzaldehyde (m.p. 107109°C), and its structure was confirmed by nuclear magnetic resonance spectrum.

io (d) A hexane solution (11.4 mfl)of n-butyllithium was dropwise added to a tetrahydrofuran (45 mfi) solution of diisopropylamine (2.81 g) at 0°C, followed by stirring for 1 hour to prepare a tetrahydrofuran solution of lithium diisopropylamide. The solution was cooled to

-50°C, and a tetrahydro furan (7.5 mfi) solution of 2chloro-4-trifluoromethylpyridine (2.81 g) was gradually added thereto, followed by stirring at the same temperature for 30 minutes. The solution was cooled to -78°C, and a tetrahydrofuran (37.5 mfi) solution of 520 benzyloxy-4-methoxy-2-methylbenzaldehyde (3.97 g) was gradually added thereto, followed by stirring at the same temperature for 1 hour. A saturated aqueous ammonium chloride solution (50 mfi) was added thereto, the temperature was raised to room temperature, the mixture was poured into a saturated aqueous sodium bicarbonate solution (50 mfl) , and extraction with ethyl acetate (150 mfi) was carried out twice. The ethyl acetate phase was fell washed with an aqueous sodium chloride solution <100 mfi) and dried over magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane5 etnyl acetate) to obtain.5.48 g (yield 96%) oi (5benzyloxy-4-methoxy-2-methylphenyl) (2-chloro-4trifluoromethyl-3-pyridyl)methanol as a red-yellow oily substance, and its structure was confirmed by nuclear magnetic resonance spectrum.

(e) (5-benzyloxy-4-methoxy-2-methylphenyl)(2-chloro*·ί

4-tri£luoromethyl-3-pyridyl)methanol (5.9 g) was t dissolved in a mixed solvent of anhydrous methylene chloride (50 mfl) and acetonitrile (5 mfi) , and tetrapropylaramonium perruthenate (95 mg), N.

jnetnylmcrpholine-N-oxxde (2.38 g) and molecular sieve 4Ά '

ϊ.

(6.5 g) were sequentially added thereto, followed by #.

stirring in a stream of argon at room temperature for three nights. The reaction mixture was distilled off under reduced pressure, the residue thus obtained was suspended in methylene chloride and subjected to filtration by celite, and the residue was adequately washed with methylene chloride (2 00 mfi) . The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (hexane25 ethyi acetate) to obtain 4.93 g (yield 84%) of 3-(5--benzy Loxy-4-methoxy-2-methylbenzoyl) -2-chloro-4~ trifluoromethylpyridine (compound No. 27; m.p. 116-

117°C), and its structure was confirmed by nuclear magnetic resonance spectrum.

SYNTHESIS EXAMPLE 7

Synthesis of 3-(2,3,4-trimethoxy-6-methylbenzoyl)-2⁵ methylthio-4-trifluoromethylpyridine (compound No. 50)

Sodium methanethiolate (0.32 g) was added to a dimethylformamide (15 mfi) solution of 0.9 g of 3-(2,3,4trimethoxy-6-methylbenzoyl)-2-chioro-4trifluoromethylpyridine (compound No. 11) at room io temperature, followed by stirring for 1 hour. The mixture was poured into water (50 mfi) , and extraction with ethyl acetate was carried out. 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 (hexaneethyl acetate) to obtain 0.54 g (yield 58%) of 3-(2,3,4tr ime thoxy-6-methylbenz oyl) -2-me thy1thio-4trifluoromethylpyridine (compound No. 50; pale yellow oily substance), and its structure was confirmed by nuclear magnetic resonance spectrum.

SYNTHESIS EXAMPLE 8

Synthesis of 5-(2,3,4-trimethoxy-6-methylbenzoyl)-3acetyl-2,6-dichloro-4-trifluoromethylpyridine (compound

No. 62) (a) 9.6 mfi (14 mmol) of n-butyllithium (1.5 M hexane solution) was dropwise added to a tetrahydrofuran (16 mfi) solution of 2.0 mfi (14 mmol) of di isopropyl amine at 0°C,

Hh followed by stirring for 30 minutes. The solution was cooled to -50°C, a tetrahydrofuran (11 rn.6) solution of

2.S g (7 mmol) of (2,3,4-trimethoxy-6-methylphenyl)(2,6dichloro-4-trifluoromethyl-3-pyridyl)methanol was added thereto, followed by stirring for 30 minutes, then the solution was cooled to -78°C, and acetaldehyde; in an excess amount was added thereto, followed by stirring for 2 hours. .30 mfi of water was added to the mixture to terminate the reaction, and tetrahydrofuran was distilled off under reduced pressure. Extraction with ethyl acetate was carried out, the organic layer was dried over anhydrous sodium sulfate and subjected to filtration, and the solvent was distilled off under reduced pressure.

The crude product thus obtained was purified by silica gel column chromatography to obtain 2.5 g (yield 78%) of (2,3.4-trimethoxy-6-niethylphenyl) (2 ,, 6-dichlorc>--5- (1hydroxyethyl)-4-trifluoromethyl-3-pyridyl)methanol.

(b) 10 g of manganese dioxide was added to a toluene (80 m6) solution of 2.3 g (5 mmol) of (2,3,4-trimethoxy20 6-methylphenyl)(2,6-dichloro-5-(1-hydroxyethyl) 4 trifIuoxomethyl-3-pyridyl)methanol obtained in step (a), followed by stirring under reflux by heating for 1 hour. The reaction solution was cooled to room temperature and then subjected to filtration, 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 (yield 66%) of 5-(2,3,4-trimetboxy-6k ft methylbenzoyl)-3-acetyl-2,6-dichloro-4trifluoromethylpyridine (compound No. 62; m.p. 109112°C).

SYNTHESIS EXAMPLE 9' ⁵ Synthesis of 4-(2,3,4-trimethoxy-6-methylbenzoyl)-2chloro-3-trif luoromethyl-5-methoxypyridine (compound No.

123) (a) 70.0 mfi (106 mmol) of n-butyllithium (1.5 M hexane solution) was dropwise added to a diethyl ether 120 mfi solution of 15.0 imS (107 mmol) of diisopropylamine at 0°C, followed by stirring for 1 hour.' The solution was cooled to -78°C, a diethyl ether 10 mfi solution of

22.1 g (102 mmol) of 2,3-dichloro-5trifluoromethylpyridine was added thereto, followed by stirring for 30 minutes, and then a toluene 40 mfi solution of 21.0 g (100 mmol) of 2,3,4-trimethoxy-6methylbenzaldehyde was added thereto, followed by stirring for 2 hours. 30 mfi of water was added to the mixture to terminate the reaction, the aqueous layer was extracted with ethyl acetate, and then the organic layer was dried over anhydrous sodium sulfate and subjected to filtration, 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 (yield 58%) of (2,3,4-trimethoxy-6methylphenyl)(2,3-dichloro-5-trifluoromethyl-4pyridyl)methanol (m.p. 95-98°C).

<8®

CM o

**» o

I a

<

(b;· 2.1 g of 5% palladium carbon was added to a methanol 200 mfi solution of 24.8 g (58.1 mmol) of (2,3,4tr ime t h oxy- 6 -me thy Ipheny 1.) (2,3 - dichloro- 5 trifluoromethyl-4-pyridyl)methanol obtained in step (a) and 9.50 mfi (68.2 mmol) of triethylamine, followed by stirring under hydrogen atmosphere for 4 hours. The mixture was subjected to filtration, 50 mfi 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 and subjected to filtration, and the solvent was distilled off under reduced pressure.

The crude product thus obtained was purified bv silica gei. column chromatography to obtain 15.9 g (yield 70%) of Ο (2,3,4-trimethoxy-6-methylphenyl) (3-chloro-5- j, trifIuoromethyl-4-pyridyl)methanol (m.p. 102--105^:’C) . **·.

(c) 45 g of manganese dioxide was added to a toluene 220 mfi solution of 15,9 g (40.6 mmol) of (2,3,4trime thoxy-6-methyIpheny1)(3-chioro-5-tri fluoromethyl-4 20 pyridyl.)methanol obtained in step (b) , followed by stirring under reflux by heating for 2 hours. The mixture was subjected to filtration, and the solvent was distilled off under reduced pressure to obtain ..14.9 g (yield 94%) of 4- (2,3,4-trimethoxy-6-methylben.zoyi) -3~

2.5 chloro-5-trifluoromethylpyridine (compound No. 3 02; m.p.

75--77°C) ., (d) 16.4 g (301 mmol) of sodium methoxide was added io

f V

Ί to a toluene 150 mfi solution of 18.5 g (47.5 mmol) of 4(2,3,4-trimethoxy-6-methylbenzoyl)-3-chloro-5trifluoromethylpyridine obtained in step (c) and 16.6 ia& (95.4 mmol) of hexamethylphosphoric triamide, followed by stirring under reflux by heating for 30 minutes. Water was added thereto to terminate the reaction, the aqueous layer was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and subjected to filtration, 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 (yield 64%) of 4-(2,3,4-trimethoxy-6methylbenzoyl)-3-methoxy-5-trifluoromethylpyridine (compound No. 122; m.p. 103-106°C).

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

(f) 1.8 mfl (19 mmol) of phosphorus oxychloride was

€·

C* added to 4 mfi of toluene and 8 mB of dimethylformamide at 0°C, followed by stirring for 10 minutes, and 4.0 g (10 miRol) of 4- (2,3,4-trimethoxy-6-methylbenzoyl)-3-methoxy5-trifluoromethylpyridine-N-oxide was added thereto, 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 terminate the reaction. The aqueous layer was extracted with ethyl acetate, and then the organic layer was dried over anhydrous sodium sulfate and subjected to filtration, and the solvent was distilled off under reduced pressure,

The crude product thus obtained was purified by silica gel column chromatography to obtain 3.57 g (yield 85%) of 4-(2,3,4-trimethoxy--6-methylbenzoyl)-2-chloro-3trif luoromethyl-5-methoxypyrxdine (compound No, .123; m.p. C# 117-119°C) . 4,_v‘

SYNTHESIS EXAMPLE 10 V

Synthesis of 4-(2,3,4- trimethoxy-6-methylbenzoyl j --2bromo-3~ trif luoromethyl-5-methoxypyr-idine (compound No.

124)

Using 7.2 g (18 mmol) of 4-(2,3,4-trimethoxy-620 inethylbenzoyl)-3-methoxy-5-trifluoromethylpyridine-Noxide, 7 xnfl of toluene, 17 mfl of dimethyiformamide and 10 g (3-5 mmol) of phosphorus oxybromide, 4.1 g (yield 49%) of 4-(2,3,4~ trimethoxy--6-methylbenzoyl)-2-bromo-3trif luoromethyl-5-metho.xypyridine (compound No. 124; m.p,

145-147°C) was obtained in the same process as in

Synthesis Example 9 step (f).

SYNTHESIS EXAMPLE 11

Synthesis of 4-(2,3,4-trimethoxy-6-methylbenzoyl)-2,3,5trichloropyridine (compound No. 186) (a) 17.2 m2 (26.7 mmol) of n-butyllithium (1.56 M hexane solution) was dropwise added to a diethyl ether (20 m2) solution of 2.7 g (26.7 mmol) of diisopropylamine at 0°C, followed by stirring for 1 hour. The solution was cooled to -78°C, a toluene solution of 4.8 g (26.7 mmol) of 2,3,5-trichloropyridine was dropwise added thereto, and then a toluene solution of 5.0 g (24.0 mmol) of 2,3,4-trimethoxy-6-methylbenzaldehyde was dropwise added thereto, followed by stirring for 30 minutes. The temperature was recovered to room temperature, and stirring was carried out further for 1 hour. 30 m2 of water was added to the mixture to terminate the reaction, and ethyl acetate was added for extraction. The organic layer was dried over anhydrous sodium sulfate and subjected to filtration, and the solvent was distilled off under reduced pressure. The crude product thus obtained was purified by silica gel column chromatography to obtain 6.7 g (yield 72%) of amorphous (2,3,4trimethoxy-6-methylphenyl)(2,3,5-trichloro-4pyridyl)methanol.

(b) 16.2 g of manganese dioxide was added to a toluene (180 m2) solution of 5.6 g of (2,3,4-trimethoxy6-methylphenyl) (2,3,5-trichloro-4-pyridyl)methanol obtained in step (a), followed by stirring under reflux

CM

CM by heating· for 3 hours. After the mixture was cooled, it. was subjected to filtration, and the solvent was distilled off under reduced pressure to obtain 4,1? g (yield 87%) of 4-(2,3,4-trimethoxy-6-methylbenzoyl)2,3,5-trichloropyridine (compound No. 186; m.p.. 60-61°C) .

SYNTHESIS EXAMPLE 11

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

4.6 -i (6.9 mmol) of triethylamine and 1.8 g of 10% palladium carbon were added to a methanol. 280 mfi solution of 17.8 g (4.6 mmol) of 4-- (2,3,4-trimethoxy-6methylbenzoyl)-2,3,5-- trichloropyridine (compound No.

186) , followed by stirring- under hydrogen atmosphere at room temperature for 7 hours. The mixture was subjected to filtration, and the solvent was distilled off under reduced pressure. The crude product thus obtained was purified by silica gel column chromatography to obtain

11.6 g (yield 72%) of 4-(2,3,4-trimethoxy-6Inethylbenzoyl) --3,5-di chloropyridine (compound No. 191; m.p. 1O9-U1°C).

SYNTHESIS EXAMPLE 13

Synthesis of 4-(2,3,4-- trimethoxy-6-methylbenzoyl.) g3y 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 were added to a toluene (60 mfi) solution of 5.0 g (1.4 mmol) of 4-(2,3,4trimethoxy-6-methylbenzoyl)-3,5-dichloropyridine β»

-ί.

I'

-5, r r i (compound No. 191), followed by stirring under reflux by heating for 5 hours. After the mixture was cooled, 50 mfl of water was added to the mixture to terminate the reaction, and ethyl acetate was added thereto for 5 extraction. The organic layer was dried over anhydrous sodium sulfate and subjected to filtration, 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 410 (2,3,4-trimethoxy-6-methylbenzoyl)-3-chloro-5methoxypyridine (compound No. 244; pale yellow oily substance).

SYNTHESIS EXAMPLE 14

Synthesis of 4-(2,3,4-trimethoxy-6-methylbenzoyl)-2,3¹⁵ dichloro-5-methoxypyridine (compound No. 193) (a) A chloroform (60 mfl) solution of 3.4 g (1 mmol) of 4-(2,3,4-trimethoxy-6-methylbenzoyl) -3-chloro-5methoxypyridine (compound No. 244) was cooled with ice,

4.1 g (1.6 mmol) of m-chloroperbenzoic acid was added thereto, followed by stirring under cooling with ice for 2 hours, and stirring was further conducted at room temperature for 2 hours. 30 mfl of a 0.5 mol/fl aqueous sodium hydroxide solution was added to the mixture to terminate the reaction, the organic layer was dried over anhydrous sodium sulfate and subjected to filtration, and the solvent was distilled off under reduced pressure to obtain 3.5 g (yield 85%) of 4-(2,3,4-trimethoxy-650 metfaylbenzoyl)-3-chloro-5-methoxypyridine-N-oxide (m.p. 16Q-166°C}.

(b) 5 mfi of dimethylformamide was added to 2..5 mfl of toluene, the mixture was cooled with ice, and 1,3 mfl (.1.4 mmol) of phosphorus oxychloride was dropwise added thereto. After the mixture was stirred under cooling with ice for 10 minutes, 2.5 g (0.7 mmol) of 4--(2,3,4trimethoxy-6-methyltoenzoyl) -3-chloro-5-methoxypyridine-Noxide was added thereto. After the mixture was stirred under cooling with ice for 30 minutes, the temperature hi was recovered to room temperature, followed by stirring for 2 hours. 3 0 mfi of water was added to the mixture to terminate the reaction, and ethyl acetate was added

CM thereto for extraction. The organic layer was dried over anhydrous sodium sulfate, subjected to filtration and ft » purified by silica gel column chromatography to obtain 2.0 g (yield 76%) of 1-- (2,3,4~trimet.hoxy-6methylbensoyl)-2,3-dichloro-5-methoxypyridine (compound No, 193; m.p. 98-99°C),

SYNTHESIS EXAMPLE 15

Synthesis of 4-(2,3,4-trimethoxy-6-methylbenzoy3)-2bromo3-chloro--_5-methoxypyr. idine (compound No. 245) mfl of dimethylformamide was added to 2.5 rri of toluene, the mixture was cooled with ice, and 0.7 g (0.2 mmol) of phosphorus oxybromide was dropwise added thereto. After the mixture was stirred under cooling with ice for 10 minutes, 0.42 g (0.1 mmol) of 4-(2,3,451 trimethoxy-6-methylbenzoyl)-3-chloro-5-methoxypyridine~Noxide obtained in Synthesis Example 14 (a) was added thereto. After the mixture was stirred under cooling with ice for 30 minutes, the temperature was recovered to room temperature, followed by stirring for 2 hours. 10 mfi of water was added to the mixture to terminate the reaction, and ethyl acetate was added thereto for extraction. The organic layer was dried over anhydrous sodium sulfate, subjected to filtration and purified by silica gel column chromatography to obtain 0.32 g (yield 65%) of 4-(2,3,4-trimethoxy-6-methylbenzoyl)-2bromo-3chloro-5-methoxypyridine (compound No. 245; m.p. 9799°C).

SYNTHESIS EXAMPLE 16

Synthesis of 4-(2,3,4-trimethoxy-6-methylbenzoyl)-3bromo-5-methylpyridine (compound No. 228) (a) 57.0 mfi (88.9 mmol) of n-butyllithium (1.56 M hexane solution) was dropwise added to a diethyl ether (110 mfi) solution of 12.5 mfi (89.2 mmol) of diisopropylamine at 0°C, followed by stirring for 60 minutes. The solution was cooled to -78°C, a toluene (80 mfi) solution of 20 g (85 mmol) of 3,5-dibromopyridine was added thereto, followed by stirring for 5 minutes, and then a toluene 50 mfl solution of 21.0 g (100 mmol) of

2,3,4-trimethoxy-6-methylbenzaldehyde was added thereto, followed by stirring for 2 hours. 50 mfi of water was added to the mixture to terminate the reaction, the aqueous layer was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and subjected to filtration, 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 (yield 31%) of (2,3,4-t.rimetho.xy~6~ methylphenyl)(3,5-dibromo-4-pyridyl)methanol (yellow oily substance).

(b) A tetrahydrofuran. (15 mfl) solution of 2.0 g (4.6 mmol) of (2,3,4-trim©thoxy-6-methylphenyl)(3,5-dibromo-4pyridyl)methanol obtained in step (a) was cooled to ~78°C, 6.0 m£ (9.4 mmol) of n-butyllithium (1.56 h hexane solution.) was dropwise added thereto, followed by stirring for 5 minutes, and 0.5 mfl (8.0 mmol) of methyl iodide was added thereto, followed by stirring for 2.5 hours. 20 mfl of water was added, and tetrahydrofuran was distilled off under reduced pressure. The aqueous layer was extracted with ethyl acetate, the organic layer was dried over anhydrous sodium sulfate and subjected to filtration, 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 (yield 25%) of <2,3,4-trimethoxy-6methyIphenyl)(3-bromo-5-methyl-4-pyridyl) methanol.

(c) 3 g of manganese dioxide was added to a toluene (30 mfl) solution of 0.43 g (1.1 mmol) of (2,3,4-t r imethoxy-6-methylphenyl) (3-bromo-5-methy1 - 4 r a•sk i ·.<

pyridyl)methanol obtained in step (b) , followed by stirring under reflux by heating for 2 hours. The mixture was subjected to filtration, the solvent was distilled off under reduced pressure, and the crude product thus obtained was purified by silica gel column chromatography to obtain 0.23 g (yield 54%) of 4-(2,3,4trimethoxy- 6-methyl benzoyl) -3~bromo-5-methylpyridine (compound Ko. 228; m.p. 88-93°C).

SYNTHESIS EXAMPLE FOR AN INTERMEDIATE

Now, Synthesis Example of 2,3,4-trimethoxy-6methylbenzaldehyde to be used as an intermediate in the above Synthesis Examples 1, 3, 9, 11 and 16 is described below.

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

A dry methylene chloride (100 mfi) solution of 128 g (0.7 mol) of 3,4,5-trimethoxytoluene was dropwise added to a dry methylene chloride 500 mfi solution of 112 g (0.84 mol) of aluminum chloride gradually under cooling with ice. The mixture was stirred at the same temperature for 45 minutes, a dry methylene chloride solution of 88.5 g (0.77 mol) of dichloromethyl methyl ether was dropwise added thereto gradually over a period of 2 hours. Stirring was conducted at the same temperature for 2 hours, and the mixture was gradually recovered to room temperature, followed by stirring at room temperature for one night. The reaction mixture was poured into Ifi of ice water, the methylene chloride phase

was separated, and the aqueous phase was extracted with 200 mfi of methylene chloride twice. The extract and the methylene chloride phase were combined together, sequentially washed with 200 mfi of water, 200 mfi of a saturated aqueous sodium bicarbonate solution and 200 mfi of a saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. A seed for a crystal was inoculated into the residue, and the y resulting crystal was collected by filtration, washed with hexane and air dried to obtain 128 g of 2,3,4trimethoxy-6-methylbenzaldehyde (m.p. 55-57°C) ,

Compounds produced by processes in accordance with Synthesis Examples 1 to 16 are shown in the following

Tables 1. to 18 .

Here, compounds represented by the formulae il-l) to (1-9) in Tables are the following compounds. Further, in Tables, Me represents a methyl group, Et represents an ethyl group, Butyl represents a butyl group, i-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 SI-1) ¹¹ “'“Ί ~·- ⁷¹' ' -J·--^- ..-- .-I —«II.·· . ... --..

NO.	ex).	R^l	(R²O	Xr/sical properties
1	2~Cl, 6-Cl	Me	4'-MeO, 5’-MeO	m.p.108-110°C
2	2-Cl, 6-Cl	Me	4'-MeO, 5’-Me	m.p.l23-I26°C
3	2-Cl, S-Cl	Me	4’-MeO, 5'-MeO, 6'-MeO	in.p. 81-83°C
4	2-Cl, 6--Cl	Me	4'-MeO	Colorless oily substance
5	Net substituted	Me	4'-MeO, 5'-MeO	yellow oily substance
6	Not substituted	Me	4'-MeO, 5'-Me	κι ,ρ. 63-65°C
7	Not substituted	Me	4'-MeO, 5'-MeO, 6¹-MeO	n.p. 59“62°C
8	Not substituted	Me	4 *-MeO	Pale yellow oily substance
9	.2-01.	Me	4'-MeO, 5'-MeO	m.p,82-86°C
10	2-Ci	Me	4'-MeO, 5'-Me	m.p.86-89°C
11	2-Ci	Me	4·-MeO, 5¹-MeO, 6’-MeO	m.p.110-112°C
12	2-Cl	Me	4'-Me, 5'-Me, 6‘-Me	m.p.88-95°C
13	2-Cl	Me	4 ’ , 5'- (-OCH₂0-)	m,p,119-122^cC
14	2-CJ	Me	4'-MeO	Pale yellow oily substance
15	2-Cl.	Et	4’-MeO, 5'-MeO, 6’-MeO
16	2-Cl	i- Propyl	4·-MeO, 5'-MeO, 6'-MeO
17	2 -Cl	Me	.1'-MeO,4'-MeO,5'-MeO,6'-MeO
18	2-Cl	Me	•4.'-MeO, 5'~EtO	m.p.89-90°C
19	2-Cl	Me	4'-MeO, 5'-i-Propyl-O-	Pale yellow oily substance
20	2-Cl	Me	i^!-MeO, 5'-Allyl-O-
21	2-Cl	Me	i *-MeO, 5'-Propargyl-0-
22	2-Cl	Me	4'-MeO, 5'-CF₃CH₂O-
23 L__	.2-Cl	Me	4 ‘ -MeO, 5 ' -c-Hexyl-O-	ks . ρ.. 85--86^cC

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Table 2

Compounds represented by Formula (1-1)
No.	(X)n	R¹	(R²)_m	Physical properties
24	2-Cl	Me	4 ’ -MeO, 5 ' - (CH₃) ₂N(CH₂) ₂0-
25	2-Cl	Me	4'-MeO, 5'-CH₃S(CH₂)₂O-
26	2-Cl	Me	4'-MeO, 5'-PhO-
27	2-Cl	Me	4'-MeO, 5'-Benzyl-0-	m.p.116-117°C
28	2-Cl	Me	4’-MeO, 5 ' -CH₃COO-
29	2-Cl	Me	4'-MeO, 5'-CH3OCOO-
30	2 -MeO, 6 -MeO	Me	4'-MeO, 5'-MeO, 6'-MeO	m.p.93-94°C
31	2-Cl, 6-MeO	Me	4'-MeO, 5'-MeO, 6'-MeO	m.p.85-87°C
32	2-MeO	Me	4'-MeO, 5'-MeO	m.p.125-127°C
33	2-i-Propyl-0-	Me	4'-MeO, 5'-MeO, 6’-MeO	Pale yellow oily substance
34	2-CF3CH3O-	Me	4'-MeO, 5'-MeO, 6'-MeO	m.p.80-82°C
35	2-CH₃O (CH₂)₂O-	Me	4'-MeO, 5'-MeO, 6'-MeO	Pale yellow oily substance
36	2-CHjS (CH₂)₂O-	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-0-	Me	4'-MeO, 5'-MeO, 6'-MeO	Pale yellow oily substance
39	2-c-Hexyl-O-	Me	4'-MeO, 5'-MeO, 6'-MeO	Pale yellow oily substance
40	2-Allyl-O-	Me	4'-MeO, 5'-MeO, 6'-MeO	m.p.85-86°C
41	2-Propargyl-O-	Me	4'-MeO, 5'-MeO, 6'-MeO	m.p.l21-124°C
42	2- (CH₃)₂N(CH₂)₂O-	Me	4'-MeO, 5'-MeO, 6'-MeO	Pale yellow oily substance
43	2-Cl, 5-Me	Me	4'-MeO, 5'-MeO, 6'-MeO	m.p.161-162°C
44	2-Cl, 5-Allyl	Me	4¹-MeO, 5'-MeO, 6'-MeO
45	2-Cl, 5-Propargyl	Me	4'-MeO, 5'-MeO, 6'-MeO
46	2-Cl, 5-CH₃O(C=O)~	Me	4'-MeO, 5'-MeO, 6¹-MeO
47	2-Cl, 5-CH₃(C=O)~	Me	4'-MeO, 5'-MeO, 6'-MeO	m.p.127-129°C

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'Τ'δ.Χ/Ι G

Compounds represented by Formula	(i-i)
No.	CX)„	R¹	(R²)_m	Physical properties
48	2-Cl, 5-Et	Me	4'-MeO, 5'-MeO, 6¹-MeO
49	2-MeO, 5-Me	Me	4'-MeO, 5'-MeO, 6'-MeO
50		Me	4'-MeO, 5’-MeO, 6'-MeO	Pale yellow oily substance
51	2-Me₂N	Me	4'-MeO, 5'-MeO, 6'-MeO	Pale yellow OX XV substance
SRO	2-Cl, 5-(CH₃)₂N(C=O)-	Me	4’-MeO, 5'-MeO, 6'-MeO
53	2 -CN	Me	4'-MeO, 5 *-MeO, 6'-MeO	m >. ρ , 140-144°C
54	2~C1, 5-Cl, 6-Cl	Me	4'-MeO. 5'-MeO, 6'-MeO	in, tu 11.4-1.16°C
c c □ -2	2-Cl, 5--Cl	Me	4'-MeO, 5'-MeO, 6'-MeO	in. p. 14.9-151°C
56	2“ΉθΟ/ “Cl	Me	4'-MeO, 5'-MeO, 6'-MeO	ra. p. 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	m, p, 1Q!~1Q4°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, 6¹-MeO
61	2-Cl, 5-CH₃O(C=O)-»6-Cl	Me	4'-MeO, 5'-MeO, 6'-MeO	m, ρ „ 107-ill°C
62	2-Cl, 5-CH₃<C=O) ”, 6-Cl.	Me	4'-MeO, 5'-MeO, 6'-MeO	ill. p - 109-112°C
63	2-Cl, 5-Bt, 6-Cl	Me	4'-MeO, 5'-MeO, 6'-MeO
64	2-Cl, 5-iCH₃)₂N(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-CH₃O (C=O) --	Me	4'-MeO, 5'-MeO, 6'-MeO
69	5-CH₃{C=O> -	Me	4’-MeO, 5'-MeO, 6'-MeO	m.p , 110-1.13 “C
70	5-Et	Me	4'-MeO, 5'-MeO, 6'-MeO

Table 4

Compounds represented by Formula (1-1)
No.	(X)„	R¹	(R²)_m	Physical properties
71	5-(CH₃) ₂N (C=O) -	Me	4'-MeO, 5'-MeO, 6¹-MeO
72	2-CH₃O (CH₂) ₂O-	Me	4'-MeO, 5'-MeO	m.p. 77-81°C
73	2-(6'-phenyl) -0-	Me	4'-MeO,5'-MeO,6'-O-(2Pyridyl)	m.p. 183-189°C
74	2-MeO	Me	4'-MeO, 5'-MeO, 6'-MeO	m.p. 81-82°C
75	2-BtO	Me	4¹-MeO, 5'-MeO, 6'-MeO	Pale yellow oily substance
76	2-MeS	Me	4'-MeO, 5'-MeO, 6'-OH	m.p. 98-102°C
77	2-OH	Me	4'-MeO, 5'-MeO, 6'-MeO	m.p. 167-173°C
78	2-NH₂	Me	4'-MeO, 5'-MeO, 6'-MeO	m.p. 115-118°C
79	2-CH₃NH	Me	4'-MeO, 5'-MeO, 6'-MeO	m.p. 150-157°C
80	2-CH₃COO	Me	4'-MeO, 5'-MeO, 6’-MeO	Pale yellow oily substance
81	2-i-Propyl-O	Me	4'-MeO, 5'-MeO, 6 ' -iPropyl-0	Pale yellow oily substance
82	2-C1, 6-C1	Et	4'-MeO, 5'-MeO, 6'-MeO	m.p. 105-108°C
83	2-Cl	Me	4'-MeO, 5'- (4-MeO-Benzyl)0	m.p. 123-125°C
84	2-Me	Me	4'-MeO,5'-MeO, 6'-MeO	m.p. 100-103°C
85	2-Me,5-C1	Me	4'-MeO,5'-MeO, 6'-MeO
86	2-Me,5-Br	Me	4'-MeO,5'-MeO, 6’-MeO

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Table 5

Compounds represented by Formula {1-2)
No.	(X)„	R¹	(R²L	Physical properties
87	2-PhO, 5-Cl	Me	4'-MeO, 5'-MeO, 6'-MeO	m.p. 147-150°C
88	2-OH, 5-C1	Me	4'-MeO, 5'-MeO, 6'-MeO

Table 6

Compounds represented by Formula (1-2)
No.	(X)_n	E?	(R³)_m	Physical properties
89	2-Cl, 5-Cl	Me	4’-MeO, 5’-MeO	m.p.120~125°C
90	2-C1, 5-Cl	Me	4'-MeO, 5‘-MeO, 6’-MeO	m.p.l0f>-109°C
91	Nut substituted	Me	4’-MeO, 5'-MeO	m.p.98-101 °C
92	Wot substituted.	Me	4'-MeO, 5’-MeO, 6¹-MeO	m.p.104.....107°C
93	2-MeO, 5-Cl	Me	4'-MeO, 5'-MeO, 6‘-MeO	m.p.l30-134°C
94	2-MeC 5-Ci.	Me	4’-MeO, 5'-MeO	m.p.l51-156°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, 6¹-MeO
98	2-Cl, 5.....Cl, 6-Cl	Me	4'-MeO, 5'-MeO	m.p.l39--141°C
99	2-Cl, 5-Cl, 6-C1	Me	4’-MeO, 5'-MeO, 6'-MeO	m.p.113 -115°C
100	5-0, 6-Cl	Me	4·-MeO, 5'-MeO	m.p.94-37³C
101	5-Cl	Me	4’-MeO, 5'-MeO	m.p.90 -91°C
102	5-Cl	Me	4’-MeO, 5’-MeO, 6’-MeO	m.p.75-77°C
103	5.....Cl, 6-Cl	Me	4’-MeO, 5'-MeO, 6'-MeO	m.p.72-74°C
104	5-CI, 6-MeO	Me	4'-MeO, 5'-MeO, 6'-MeO	m.p.l43-i46°C
105	5-Cl, 6-MeO	Me	4.' -MeO, 5 ' -MeO	m.p.112-.I15°C
106	5-0, 6-EtO	Me	4’-MeO, 5'-MeO, 6'-MeO	m.p.82-84^cC
107	6 -MeO	Me	4' -MeO, 5'-MeO, 6'-MeO ......................	Pale yellow oily substance
108	5-Cl, 5-n-Propyl-O	Me	4’-MeO, 5'-MeO, 6'-MeO	Pale yellow oily substance
109	6-BtO	Me	4’-MeO, 5'-MeO, 6’-MeO	Pale yellow oily substance
110	5-0, 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~Butyl-0	Me	4'-MeO, 5’-MeO, 6'-MeO	Pale yellow oily substance

Λ * ’·

Table 7

Compounds represented by Formula (1-2)
No.	(X)n	R^l	(R²)_m	Physical properties
113	5-Cl, 6-Propargyl-O	Me	4'-MeO, 5'-MeO, 6'-MeO	m.p.131-133°C
114	5-Cl, 6-n-Pentyl-O	Me	4'-MeO, 5¹-MeO, 6'-MeO	Pale yellow oily substance
115	5-Cl, 6-OH	Me	4'-MeO, 5'-MeO, 6'-MeO	152-154°C
116	6-n-Pentyl-O	Me	4'-MeO, 5'-MeO, 6'-MeO	Pale yellow oily substance
117	5-Cl, 6-CH₃S(CH₂)₂0	Me	4'-MeO, 5'-MeO, 6'-MeO	m.p.62-64°C
118	5-Cl, 6-Allyl-O	Me	4’-MeO, 5'-MeO, 6'-MeO	Pale yellow oily substance
119	5-Cl, 6-CH₃O(CH₂) ₂0	Me	4'-MeO, 5'-MeO, 6'-MeO	m.p.78-80°C
120	2-MeO, 5-MeO	Me	4'-MeO, 5'-MeO, 6'-MeO	m.p.135-139°C
121	2-MeO	Me	4'-MeO, 5'-MeO, 6'-MeO	m.p.97-100°C
122	5-MeO	Me	4'-MeO, 5'-MeO, 6'-MeO	m.p.103-106°C
123	2-Cl, 5-MeO	Me	4'-MeO, 5'-MeO, 6'-MeO	m.p.H7-119°C
124	2-Br, 5-MeO	Me	4'-MeO, 5’-MeO, 6'-MeO	m.p.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-Propargyl,5-MeO	Me	4'-MeO,5'-MeO, 6'-MeO
130	2-EtO,5-MeO	Me	4’-MeO,5'-MeO, 6’-MeO	m.p.110-112°C
131	2-CN,5-MeO	Me	4'-MeO,5’-MeO, 6'-MeO	m.p.117-120°C
132	2-MeS,5-MeO	Me	4'-MeO,5'-MeO, 6'-MeO	m.p.154-159°C
133	5-Me	Me	4'-MeO,5'-MeO, 6'-MeO	m.p. 98~105°C
13 4	5-Br	Me	4'-MeO,5'-MeO, 6'-MeO
135	5-F	Me	4'-MeO,5'-MeO, 6'-MeO

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Table 13

No.	Formula	(XL	R¹	(r²)_p	R~	Phys ίcal properties
167	(1-7)	2-Cl,4-CF_3< 6-CFj	Me	5'-MeO, 6'-MeO	MeO	ΤΏ,ρ , 117-1X3°C
168	(1-7)	2-CF₃, 4-CFj, 5-Me	Me	5'-MeO, 6'-MeO	MeO
169	(1-7)	2-CFs , 4-CF3 , 5-Et	Me	5¹-MeO, 6'-MeO	MeO
170	(1-7)	2-CFj, 4-CF3, 5-Allyl	Me	5'-MeO, 6’-MeO	MeO
171	(1-7)	2 -CF₃, 4-CF₃, 5-n-Propyl	Me	5'-MeO, 6'-MeO	MeO
172	(1-7)	2-CFj, 4-CF3,5-Propargyl	Me	5'-MeO, 6'-MeO	MeO
173	(1-7)	2-CFj, 4-CF3, 5-Me,6-Cl	Me	5'-MeO, 6’-MeO	MeO
17 4	(X-7)	2-CF₃,4-CF₃, 5 -E t,6-C1	Me	5'-MeO, 6'-MeO	MeO
175	(1-7)	2-CF₃,4-CF₃,5-Allyl, 6-Cl	Me	5'-MeO, 6'-MeO	MeO
176	(X~7)	2-CF₃,4-CF₃, 5-n-Propyl,6-Cl	Me	5'-MeO, 6'-MeO	MeO
177	(1-7)	2-CF₃,4-CF₃, 5-Propargyl,6-Cl	Me	5'-MeO, 6'-MeO	MeO
178	(1-7)	2-CF3,4-CF₃	Me	5'-MeO, 6'-MeO	MeO
179	(I--7)	2-CF3,5-CF3,6--C1	Me	5'-MeO, 6¹-MeO	MeC
180	(X-7)	2-CF3,5-CF3	Me	5'-MeO, 6'-MeO	MeO
181	(1-7)	2-CFj,4-Me,5-CF3	Me	5'-MeO, 6’-MeO	MeO
182	(1-7)	2-CFj, 4-Et, 5-CFy	Me	5'-MeO, 6'-MeO	MeO
183	(1 - /)	2-CF₃,4-Allyl,5-CP₃	Me	5’-MeO, 6*-MeO	MeO
184	( I--7}	2-CF3,4-n-propyl,5-CF₃	Me	5'-MeO, 6'-MeO	MeO i
185	(1 -7)	2CF₃,4-propargyl,5~CF₃	Me	5'-MeO, 6'-MeO	MeO
186	(1 - 8 )	2-Cl,3-Cl,5-Cl	Me	5'-MeO, 6'-MeO	MeO	m.p. 60-61°C
187	(I - 8 ) .	2-MeO,3-Cl,5-Cl	Me	5'-MeO, 6'-MeO	i m.p. MeO I ( 128-134°C

Table 14

No.	Formula	(X)„	R¹	(r²)_p	R³	Physical properties
188	(1-8)	2-EtO,3-Cl,5-Cl	Me	5'-MeO, 6'-MeO	MeO	Pale yellow oily substance
189	(1-8)	2-MeO,3-MeO,5-Cl	Me	5'-MeO, 6¹-MeO	MeO	Pale yellow oily substance
19C	(1-8)	2-MeO,3-MeO	Me	5'-MeO, 6'-MeO	MeO	Pale yellow oily substance
191	(1-8)	3-Cl.5-Cl	Me	5'-MeO, 6'-MeO	MeO	m.p. 109-lll°C
192	(1-8)	3-Cl	Me	5'-MeO, 6'-MeO	MeO	m.p.90-94°C
193	(1-8)	2-Cl,3-Cl,5-MeO	Me	5'-MeO, 6'-MeO	MeO	m.p.98-99°C
194	(1-8)	2-Cl,3-Cl,5-EtO	Me	5'-MeO, 6’-MeO	MeO	m.p. 110-114°C
195	(1-8)	2-Cl,3-MeO,5-MeO	Me	5'-MeO, 6'-MeO	MeO
196	(1-8)	2-Cl,3-EtO,5-MeO	Me	5'-MeO, 6'-MeO	MeO
197	(1-8)	3-MeO	Me	5'-MeO, 6'-MeO	MeO
198	(1-8)	3-EtO	Me	5'-MeO, 6'-MeO	MeO
199	(1-8)	2-Cl,3-MeO,5-Cl	Me	5'-MeO, 6'-MeO	MeO	m.p.80-86°C
200	(1-8)	2-Cl,3-EtO,5-Cl	Me	5'-MeO, 6’-MeO	MeO	Pale yellow oily substance
201	(1-8)	3-Br	Me	5'-MeO, 6'-MeO	MeO	m.p.l06-107°C
202	(1-8)	3-Br,5-Br	Me	5'-MeO, 6’-MeO	MeO	m.p.1Q8-11O°C
203	(1-8)	3-Br,5-MeO	Me	5'-MeO, 6’-MeO	MeO	Pale yellow oily substance
204	(1-8)	2-F,3-F,5-F	Me	5'-MeO, 6'-MeO	MeO
205	(1-8)	2-MeO,3-F,5-F	Me	5'-MeO, 6'-MeO	MeO
206	(1-8)	2-EtO,3-F,5-F	Me	5'-MeO, 6'-MeO	MeO
207	(1-8)	2-MeO,3-MeO,5-F	Me	5'-MeO, 6'-MeO	MeO
208	(1-8)	3-F,5-F	Me	5'-MeO, 6'-MeO	MeO
209	(1-8)	3-F	Me	5'-MeO, 6'-MeO	MeO
210	(1-8)	3-Me,5-MeO	Me	5'-MeO, 6¹-MeO	MeO	Pale yellow oily substance

Table 15

No ,	Formula	(X)_n	R¹	(r²)_?	P?	— Physical properties
211	il~S)	2-Cl,3-Me,5-MeO	Me	5'-MeO, 6'-MeO	MeO	Pale yellow oily substance
212	(1-8)	2-Br,3-Me,5-MeC	Me	5'-MeO, 6'-MeO	MeO i
213	(1-8)	3-Me,5-Me	Me	5’-MeO, 6’-MeO	MeO	m.p . 117-122°C
214	(1-8)	2-Cl,3-Me,5-Me	Me	5'-MeO, 5'-MeO	MeO
215	(1-8)	2-Br,3-Me,5-Me	Me	5'-MeO, 5'-MeO	MeO
216	(1-8)	3-Et,5-MeO	Me	5'-MeO, S'-MeO	MeO
217	(1-8 5	3-Allyl,5-MeO	Me	5'-MeO, S'-MeO	MeO
218	(1-8)	3-n-Propyl,5-MeO	Me	5'-MeO, 5'-MeO	MeO
219	(1-8)	3-Propargyl,5-MeO	Me	5'-MeO, 5'-MeO	MeO
220	(1-8)	2-Cl,3-Et,5-MeO	Me	5'-MeO, 6'-MeO	MeO
221	(1-8)	2-Cl,3-Allyl,5-MeO	Me	5'-MeO, 6'-MeO	MeO
222	(1--8)	2-Cl,3-n-Propyl,5-MeO	Me	5'-MeO, 6'-MeO	MeO
223	(1-8)	2-Cl,3 -Propargyl,5-MeO	Me	5'-MeO, 6'-MeO	MeO
224	(1-8)	2-Br,3-Et,5-MeO	Me	5’-MeO, 6'-MeO	MeO
225	(1-8)	2-Br,3-Allyl,5-MeO	Me	5'-MeO, 6'-MeO	MeO
226	(1--8)	2-Br,3-n-Propyl,5-MeO	Me	5'-MeO, 6'-MeO	MeO
227	(1-8)	2-Br,3-Propargyl,5-MeO	Me	5’-MeO, 6'-MeO	MeO
228	(1-8)	3-Me,5-Br	Me	5'-MeO, 6'-MeO	MeO	ii i . p . 88-93 °C
229	(1-8)	3-Et,5-Br	Me	5'-MeO, 6'-MeO	MeO
230	(1-8 )	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	(.1-8)	3-Propargyl, 5-Br	Me	5¹-MeO, 6’-MeO	MeO
233	(1-8)	3-Me,5-Br,6-Cl	Me	5¹-MeO, 6'-MeO	MeO
234	(1-8)	3-Et,5-Br,5-Cl	Me	5'-MeO, 5'-MeO	MeO

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Table 16

No .	Formula	(χ)„	R¹	(R²)_P	R³	Physical properties
235	(1-8)	3-Allyl,5-Br,6-Cl	Me	5’-MeO, 6'-MeO	MeO
236	(1-8)	3-n-Propyl,5-Br,6-C1	Me	5'-MeO, 6'-MeO	MeO
237	(1-8)	3-Propargyl,5-Br,6-Cl	Me	5'-MeO, 6'-MeO	MeO
238	(1-8)	3-Me,5-Br,6-Br	Me	5'-MeO, 6'-MeO	MeO
239	(1-8)	3-Et,5-Br,6-Br	Me	5'-MeO, 6'-MeO	MeO
240	(1-8)	3-Allyl,5-Br,6-Br	Me	5’-MeO, 6'-MeO	MeO
241	(1-8)	3-n~Propyl,5-Br,6-Br	Me	5'-MeO, 6'-MeO	MeO
242	(1-8)	3-Propargyl,5-Br,6-Br	Me	5'-MeO, 6'-MeO	MeO
243	(1-8)	3-MeO,5-MeO	Me	5'-MeO, 6'-MeO	MeO	Red oily substance
244	(1-8)	3-MeO,5-Cl	Me	5'-MeO, 6'-MeO	MeO	Pale yellow oily substance
245	(1-8)	2-Br,3-Cl,5-MeO	Me	5'-MeO, 6'-MeO	MeO	m.p. 97-99°C
246	(1-8)	2-Br,3-Br,5-Br	Me	5'-MeO, 6'-MeO	MeO
247	(1-8)	2-Cl,3-Br,5-Br	Me	5'-MeO, 6'-MeO	MeO
248	(1-8)	2-Br,3-Cl,5-Cl	Me	5'-MeO, 6'-MeO	MeO
249	(1-8)	2-Cl,3-MeO,5-Cl,6-Cl	Me	5'-MeO, 6'-MeO	MeO	Yellow oily substance
250	(1-8)	2-Br,3-MeO,5-Cl,6-Cl	Me	5'-MeO, 6'-MeO	MeO	Yellow oily substance
251	(1-8)	3-EtO,5-EtO	.Me	5'-MeO, 6'-MeO	MeO	m.p. 106-109°C
252	(1-8)	3-EtO,5-Cl	Me	5'-MeO, 6'-MeO	MeO	m.p. 98.5-99.5°C
253	(1-8)	2-Br,3-EtO,5-Cl	Me	5'-MeO, 6'-MeO	MeO
254	(1-8)	2-Br,3-Cl,5-EtO	Me	5'-MeO, 6'-MeO	MeO	m.p. 113-115°C
255	(1-8)	2-Cl,3-Br,5-EtO	Me	5'-MeO, 6'-MeO	MeO
256	(1-8)	2-Br,3-Br,5-EtO	Me	5'-MeO, 6'-MeO	MeO
257	(1-8)	2-Br,3-Cl,5-Cl	Me	5'-MeO, 6'-MeO	MeO
258	(1-8)	2-C1,3-EtO,5-Cl,6-Cl	Me	5’-MeO, 6’-MeO	MeO

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No.	Formula	tx)„	R¹	(r²)_p	P?	Physical properties
259	(1-8)	2-Br,3-EtO,5-Cl,6-Cl	Me	5'-MeO, 6'-MeO	MeO
260	(1-8)	2-Cl,3-EtO,5-Cl,6-Br	Me	5'-MeO, 6'-MeO	MeO
261	(1-8)	2-Br, 3-EtO, 5-Cl, 6'-sr	Me	5'-MeO, 6'-MeO	MeO
262	(1-8)	2-F,3-F,5-F, 6-F	Me	5'-MeO, 6'-MeO	MeO	«1. p . 85-87°C
263	(1-8 )	2-Br,3-F,5-F	Me	5'-MeO, 6'-MeO	MeO
264	(1--8)	2-F,3-Me,5-F	Me	5'-MeO, 6'-MeO	MeO
265	(1-8)	2-Br, 3-F, 5-F,6 Br	Me	5'-MeO, 6'-MeO	MeO
266	(1-8)	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	(1-8)	2-C1,3-C1,5-Cl,6-Cl	Me	5'-MeO, 6'-MeO	MeO
269	(1-8)	3-Br,5-F	Me	5'-MeO, 6'-MeO	MeO
270	(1-8)	2-Br,3-F,5-F,6-F	Me	5'-MeO, 6'-MeO	MeO
271	(1--8)	3-F, 5-CH₃	Me	5'-MeO, 6'-MeO	MeO
272	(1-8)	3-Cl,5-CH3	Me	5'-MeO, 6'-MeO	MeO	m.p. 84-88°C
273	(1-8)	3-F,5-MeO	Me	5'-MeO, 6'-MeO	MeO !
274	(1-8)	2-Cl, 3-CF3,6-CF-,	Me	5'-MeO, 6'-MeO	MeO	m.p. 85-83°C
275	(1-8)	3-CF₃, 6-CF3	Me	5'-MeO, 6'-MeO	MeO
276	(1-8)	3-CF₃₍ 5-Me, 6-CF3	Me	5'-MeO, 6'-MeO	MeO
277	(1-8)	3-CP3, 5-Et, 6-CFj	Me	5'-MeO, 6'-MeO	MeO
278	(1-8)	3-CF₃, 5-Allyl,6-Cf3	Me	5'-MeO, 6'-MeO	MeO
279	(1-8)	3-CF3, 5-n-Propyl,6-CF₃	Me	5'-MeO, 6'-MeO	MeO
280	(1-8)	3-CF₃,5-Propargyl,6-CF3	Me	5'-MeO, 6'-MeO	MeO
281	(1-8)	2-Cl,3-CF₃₍ 5-CF3,6-Cl	Me	5'-MeO, 6'-MeO	MeO
282	(1-8)	2-C1,3-CF₃,5-CFy	Me	5'-MeO, 6'-MeO	MeO

Table 18

No.	Formula	(X)„	R¹	(r²)_p	R³	Physical properties
283	(1-8)	3-CF₃,5-CF₃	Me	5'-MeO, 6'-MeO	MeO
284	(1-9)	3-Cl,5-C1,6-Cl	Me	5'-MeO, 6'-MeO	MeO	m.p . 144-147°C
285	(1-9)	3-F,5-F,6-F	Me	5'-MeO, 6'-MeO	MeO
286	(1-9)	3-Br,5-Br	Me	5'-MeO, 6'-MeO	MeO	Pale yellow oily substance
287	(1-1)	2-MeO	Me	5'-C-Hexyl-0	MeO	m.p. 97-100°C
288	(1-8)	2-Me,3-Cl,6-Cl	Me	5' -MeO	MeO	m.p. ni-ii3°e
289	(1-8)	2-Me,3-Cl,6-Cl	Et	5'-MeO	MeO	m.p. 88-94°C
290	(1-8)	2-Me,3-Cl	Me	5'-MeO	MeO	m.p. 117-118°C
291	(1-8)	2-C1,3-Br,5-MeO	Me	5'-MeO,6'-MeO	MeO	Brown oily substance
292	(1-8)	2-Br,3-Br,5-MeO	Me	5'-MeO,6'-MeO	MeO	Yellow oily substance

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Compounds represented by the formula (X) co be used as an intermediate, produced by processes in accordance with Synthesis Examples 1, 3, 5, 6, 8, 9, 11 and 16, are shown in the following Tables 19 to 36.

Here, compounds represented by the general formulae (X-l) to (X-9) in Tables are the following compounds.

Further, in Tables, Me represents a methyl group, Et represents an ethyl group, Butyl represents a butyl, group, i-Propyl represents an isopropyl group. Ph s ^k 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.

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Table 19

Compounds represented by Formula (X-l)

No .	(XL	R¹	(R²)_m	Physical properties
1	2-Cl, 6-Cl	Me	4'-MeO, 5'-MeO	Viscous substance
2	2-Cl, 6-Cl	Me	4’-MeQ, 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‘-MeC	Viscous substance
5	Not substituted	Me	4·-MeO, 5¹-MeO
6	Not substituted	Me	4'-MeO, 5' -Me
7	Not substituted	Me	4’-MeO, 5'-MeO, S'-MeO	ir.,. p. 132-135°C
8	Not substituted	Me	4¹-MeO
9	2-Cl	Me	4’-MeO, 5'-MeO
10	2-Cl	Me	4’-MeO, 5 ' -Me
11	2-Cl	Me	4¹-MeO, 5'-MeO, 6'-MeO	Viscous substance
12	2-Cl	Me	4'-Me, 5'-Me, 6'-Me	All . p . 125-127°C
13	2-Cl	Me	4 S 5(~OCH₂O~) .....	IP. p, 127-130°C
14	2-Cl	Me	4'-MeO
15	2-ei	Et	4'-MeO, 5'-MeO, 6'-MeO
16	2-01	i- Prqpyl	4’-MeO, 5'-MeO, 6'-MeO
17	2 -Cl	Me	3’-MeO,4'-MeO,5'-MeO,6¹-MeO
18	2-Cl	Me	4‘-MeO, 5'-EtO	Viscous substance
19	2-CI	Me	4 -MeO, 5'-i-Propyl-O-	Viscous substance
20	2 ~Cl	Me	4‘-MeO, 5'-Allyl-O-
21	2-Cl	Me	4'-MeO, 5¹-Propargyl-O-
22	2-CI	Me	4 -MeO, 5'-CF₃CH₂O-
23	2-CI	Me	4‘-MeO,- 5 ' -c-Hexyl-O-	Viscous substance

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Table 20

Compounds represented by Formula (X-l)
No.	(x)„	R¹	(R²)m	Physical properties
24	2-Cl	Me	4 ' -MeO, 5 ' - (CH₃) ₂N(CH₂) ₂0-
25	2-Cl	Me	4’-MeO, 5 ' -CH₃S (CH₂) ₂O-
26	2-Cl	Me	4'-MeO, 5'-PhO-
27	2-Cl	Me	4'-MeO, 5'-Benzyl-0-	Viscous substance
28	2-Cl	Me	4'-MeO, 5 ’ -CH₃COO-
29	2-Cl	Me	4 ' -MeO, 5 ' -CH₃OCOO-
30	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-i-Propyl-O-	Me	4'-MeO, 5'-MeO, 6'-MeO
34	2-CF₃CH₂O-	Me	4'-MeO, 5'-MeO, 6'-MeO
35	2-CH3O (CH₂)₂O-	Me	4’-MeO, 5'-MeO, 6’-MeO
36	2-CH3S (CH₂)₂O-	Me	4'-MeO, 5'-MeO, 6'-MeO
37	2-PhO-	Me	4'-MeO, 5'-MeO, 6'-MeO
38	2-3enzyl-0-	Me	4'-MeO, 5'-MeO, 6'-MeO
39	2-c-Hexyl-O-	Me	4'-MeO, 5'-MeO, 6'-MeO
40	2-Allyl-O-	Me	4'-MeO, 5'-MeO, 6'-MeO
41	2-Propargyl-0-	Me	4'-MeO, 5'-MeO, 6'-MeO
42	2-(CH₃)₂N(CH₂)₂O-	Me	4¹-MeO, 5'-MeO, 6'-MeO
43	2-Cl, 5-Me	Me	4'-MeO, 5'-MeO, 6'-MeO
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-CH₃O(C=O)-	Me	4'-MeO, 5'-MeO, 6'-MeO
47	2-Cl, 5-CH₃(C=O)~	Me	4'-MeO, 5'-MeO, 6'-MeO

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Table

Compounds represented by Formula (X-l)
No.	(X)_B	R¹	(R²),	Pnysicax 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
50		Me	4'-MeO, 5¹-MeO, 6'-MeO
51	2-Me₂N	Me	4'-MeO, 5'-MeO, 6'-MeO
52	2-Cl, 5-(CH₃)₂N(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	Vxscoiis substance
55		Me	4‘-MeO, 5'-MeO, 6'-MeO
56	2-MeO, 5-C1	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-C'l	Me	4'-MeO, 5'-MeO, 6'-MeO	Viscous substance
60	2-Cl, 5-Propargyl, 6-C1	Me	4'-MeO, 5'-MeO, 6'-MeO
61	2 -Cl, 5 - CHjO(C=O)-,6-Cl	Me	4'-MeO, 5'-MeO, 6'-MeO	.m_?, p. 133~X35°C
62	2-Cl, 5-CH₃CH(OH) - , 6-Cl	Me	4'-MeO, 5'-MeO, 6'-MeO	in. ρ.. 141~1S8°C
63	2-Cl, 5-Et, 6-Cl	Me	4'-MeO, 5'-MeO, 6'-MeO
64	2-Cl, 5-(CH₃)₂N(C=O)-	Me	4'-MeO, 5'-MeO, 6’-MeO	................ ¹
65	5 -Me	Me	4'-MeO, 5'-MeO, 6'-MeO
66	5-Allyl	Me	4'-MeO, 5'-MeO, 6'-MeO
67	5-Propargyl	Me	4'-MeO, 5'-MeO, 6’-MeO
68	5~CH₃0(C=0) -	Me	4'-MeO, 5'-MeO, 6'-MeO
69	5-CHj(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-l)
No.	(X)„	R¹	(R²)_m	Physical properties
71	5- (CHj) ₂N(C=O) -	Me	4’-MeO, 5'-MeO, 6'-MeO
72	2-CH₃0(CH₂)₂0-	Me	4'-MeO, 5'-MeO
73	2-(6¹-phenyl)-0-	Me	4'-MeO,5¹-MeO,6¹-0-(2-Pyridyl)
74	2-MeO	Me	4'-MeO, 5'-MeO, 6’-MeO
75	2-EfcO	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, 6¹-MeO
78	2-NH₂	Me	4'-MeO, 5'-MeO, 6'-MeO
79	2-CH3NH	Me	4'-MeO, 5'-MeO, 6'-MeO
80	2-CH3COO	Me	4'-MeO, 5'-MeO, 6'-MeO
81	2-i-Propyl-0	Me	4 ' -MeO, 5¹ -MeO, 6' -i-Propyl-0
82	2-C1, 6-C1	Et	4'-MeO, 5'-MeO, 6'-MeO
83	2-C1	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

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Table 23

Compounds represented by Formula (X-2)
No.	(X)n	R¹	(R^Z)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, 6¹-MeO

Table 24

Compounds represented by Formula (X-2)
No.	(XI,	R^l	(B	2 ) J m				Physical. properties
89	2-Cl,	5-Cl	Me	4 ‘	-MeO, 5'	-MeO			m.p.134- 136 °C
90	2-Cl,	5-Cl	Me	A'	-MeO, 5'	-MeO,	6 ’	-MeO	m.p.162-165°C
91	Not substituted	Me	47	-MeO, 5'	-MeO
92	Not substituted	Me	4 ‘	-MeO,. 5 '	-MeO,	6 ¹	-MeO	m.p.101-136°C
93	2-MeO	, 5-Cl	Me j 4 '	-MeO, 5'	-MeO,	6'	-MeO
94	2-MeO	5-CI	Me	4 ¹	-MeO, 5'	-MeO
95	2~3r,	5-Cl	Me	4 ‘	-MeO, 5'	-MeO,	6 '	-MeO
95	2 -MeS	, 5-C1	Me	4-	-MeO, 5'	-MeO,	6 ’	-MeO
97	2-CK,	5 -Cl	Me	' 4 ¹	-MeO, 5'	-MeO,	6 ’	-MeO
98	2-Cl,	5-C1, 6-C1	Me	4 ³	-MeO, 5'	-MeO			ro.p.l56-158°C
99	2-Cl,	5-C1, 6-C1	Me	4'	-MeO, 5'	-MeO,	6'	-MeO	rn.p. 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	m.p. 102--105°C
103	5-C1,	6-Cl	Me	4 ’	-MeO, 5'	-MeO,	6'	-MeO	m.p.95-98°C
104	5-C1,	6 - MeO	Me	4 ^!	-MeO, 5'	-MeO,	6'	-MeO
105	5-Cl,	6-MeO	Me	4	-MeO, 5'	-MeO
105	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^s	-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	R¹	(R²)_m	Physical properties
113	5-Cl, 6-Propargyl-O	Me	4'-MeO, 5¹-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, 6¹-MeO
116	6-n-Pentyl-O	Me	4'-MeO, 5'-MeO, 6'-MeO
117	5-Cl, 6-CH₃S (CH₂)₂0	Me	4'-MeO, 5·-MeO, 6'-MeO
118	5-Cl, 6-Allyl-O	Me	4'-MeO, 5'-MeO, 6’-MeO
119	5-Cl, 6-CH₃O(CH₂) ₂0	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	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-Propargyl,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

X' «ν €* j

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Table 26

Compound represented, by Formula (X-3)
No.	(Χ)„	R¹	. ₂. ί Physical : properties
136	6 -Cl	Me	” © -1 !Viscous 4'-MeO, 5’-MeO, 6’-MeO . substance

Table 27

Compound represented by Formula (X-4)
No.	fx)_n	R¹	(R²)_m : Physical iproperties
137	Not substituted	Me	4'-MeO, 5’-MeO, 6’-MeO \ ,,1..-, —

Table 2 8

Compound represented by Formula (X-5)
No.	(XL	R¹	(R²), Physic»! i properties
138	5-Cl, S-Cl	Me	i TR . p . 4’-MeO, 5’-MeO, 6'-MeO ί71~73“Ο

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Table 29

Compounds represented by Formula (X-6)
No.	(X.)_a	R¹		Physical properties
139	4-Me	Me	4¹-MeO,5¹-MeO, 6¹-MeO
140	4-Me,5-Cl	Me	4'-MeO,5'-MeO, 6'-MeO
141	4-Ma,5-Br	Me	4'-MeO,5'-MeO, 6'-MeO

Table 30

No.	Formula	(X)_n	R¹	(r²)_p	R³	Physical properties
142	(X-7)	2-MeO	Me	5'-MeO	MeO	Viscous substance
143	(X-7)	2-Cl,4-C1	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	5¹-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-C1	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-C1	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-C1	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
159	(X-7)	2-MeO,4-Me,5-Br	Me	5'-MeO, 6'-MeO	MeO
160	(X-7)	2-Me,4-Cl	Me	5'-MeO, 6'-MeO	MeO
161	(X-7)	2-Me,4-C1,5-C1	Me	5'-MeO, 6'-MeO	MeO
162	(X-7)	2-Me,4-C1,5-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-C1	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-CF₃,4-CF₃, 6-Cl	Me	5'-MeO, 6'-MeO	MeO

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Table 31

No.	Formula	(X)„	R¹	(R²)_p	s !Physical
P?	properties
167	(X-7)	2-Cl,4-CF₃,6-CF,	Me	5*-MeO,	6'-MeO	MsO	Viscous substance
168	(X-7)	2-CF₃, 4-CFj, 5.....Me	Me	5'-MeO,	6'-MeO	MeO
169	(X-7)	2-CF3 ,4-CFj ,5-Et	Me	5'-MeO,	6'-MeO	MeO
170	(X-7)	2-CF3, 4-CFj, 5-Allyl	Me	5'-MeO,	6'-MeO	MeO
171	;x~7)	2-CF₃, 4-CFj , 5-n-Propyl	Me	5'-MeO,	6'-MeO	Meo
172	(X-7)	2-CF3, 4-CF₃, 5-Propargyl	Me	5'-MeO,	6 ’ -MeO	MeO
173	(X-7)	2-CF5, 4-CF₃, 5-Me,6-Cl	Me	5'-MeO,	6'-MeO	1 MeO j
174	(X-7)	2-CP₃,4-CFj, 5-St,6-Cl	Me	5'-MeO,	6'-MeO	.................I.................-................. MeO i
175	(X-7)	2-CFj,4-CF3, 5- Allyl,6-C1	Me	5'-MeO,	6'-MeO	MeO
176	(X-7)	2-CF₃,4-CF₃, 5-n-Propyl,6-C1	Me	5'-MeO,	6’-MeO	MeO
177	(X-7)	2-CF₃,4-CF₃, 5-Propargyl,6~Cl	Me	5’-MeO,	6'-MeO	MeO	........-
17 8	(X-7)	2-CF₃,4-CF₃	Me	5'-MeO,	6'-MeO	MeO !
179	(X-7)	2-CF₃,5-CF₃,6-Cl	Me	5'-MeO,	6’-MeO	............!.......... MeO ί
180	(X-7)	2-CF3,5-CFj	Me	5'-MeO,	6'-MeO	—,— ...................... MeO j
181	(X-7)	2-CF₃,4-Me,5-CP,»	Me	5'-MeO,	6'-MeO	MeO i
182	(X-7)	2-CF₃,4-Ht, S-CB’j	Me	5'-MeO,	6'-MeO	MeO 5
183	(X-7)	2-CF₃,4-Allyl, 5-CF₃	Me	5'-MeO,	6'-MeO	^k ......t........ MeC [
184	(X-7)	2-CF3,4-n-propyi,5-CF₃	Me	5'-MeO,	6'-MeO	MeO j
185	(X-7)	2-CFj, 4-propargy.L, 5-CF₃	Me	5'-MeO,	6'-MeO	MeO
186	(X-8)	2 -Cl,3-Cl,5-Cl	Me	5¹-MeO,	6'-MeO	MeO	Amorphous
187	(X-8')	2-MeO,3-C1,5~Cl	Me	5'-MeO,	6¹-MeO	MeO

Table 32

No.	Formula	(X)„	R¹	(r²)_p	R³	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-C1.5-C1	Me	5'-MeO, 6	-MeO	MeO	m.p. 136-140°C
192	(X-8)	3-C1	Me	5'-MeO, 6	-MeO	MeO	m.p. 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-C1,3-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-C1,3-MeO,5-Cl	Me	5'-MeO, 6	-MeO	MeO
200	(X-8)	2-C1,3-EtO,5-Cl	Me	5'-MeO, 6	-MeO	MeO
201	(X-8)	3-Br	Me	5'-MeO, 6	-MeO	MeO	m.p. 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	m.p. 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>„ ......	R¹	(R²)_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	CX -8)	3-Me,5-Me	Me	5'-MeO,	6¹-MeO	MeO
214	(X-8)	2-Cl,3-Me,5-Me	Me	5'-MeO,	6'-MeO	MeO
215	(X- 8 j	2-Br, 3-JSJe, 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)	2-C1,3-Et,5-MeO	Me	5’-MeO,	6'-MeO	MeO
221	(X-8)	2-C1,3-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-C1,3-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	5¹-MeO,	6'-MeO	MeO
226	(X-8)	2-Br,3-n-Propyl, 5-MeO	Me	5'-MeO,	6'-MeO	MeO
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
23 0	(X-8)	3-Allyl,5-Br	Me	5'-MeO,	6'-MeO	MeO
231	(X-8)	3-n-Propyl,5-Br	Me	5’-MeC,	6’-MeO	MeO
232	(X-8)	3-Propargyl,5-Br	Me	5'-MeO,	6¹-MeO	Me .
233	(X-8)	2-Me,5-Br,6-Cl	Me	5'-MeO,	6'-MeO	MsO
234	(X-8)	3-Et,5-Br,6-Cl	Me	5'-MeO,	6¹-MeO	MeO

Table 34

No .	Formula	(x).	R¹	a	R³	Physical properties
235	(X-8)	3-Allyl,5-Br,6-Cl	Me	5¹-MeO, 6¹-MeO	MeO
236	(X-8)	3-n-Propyl,5-Br,6-Cl	Me	5'-MeO, 6¹-MeO	MeO
237	(X-8)	3-Propargyl,5-Br,6-Cl	Me	5¹-MeO, 6¹-MeO	MeO
238	(X-8)	3-Me,5-Br,6-Br	Me	5¹-MeO, 6¹-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	5¹-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

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Table 35

No.	Formula	(X)„	R¹	(r²)_p		Physical properties
259	(X-8)	2-Br,3-EtO,5-C1,6-C1	Me	5'-MeO, 6’-MeO	MeO
260	(X-8)	2-Cl,3-EtO,5-C1.6-Br	Me	5'-MeO, 6'-MeO	KeO
261	(X-8;	2-Br,3-EtQ,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	KeO
2 65	(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	Mec
268	(X-8)	2-01,3-01,5-01,6-01	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-CH₃	Me	5'-MeO, 6'-MeO	MeO
272	(X-8)	3-Cl,5-CH₃	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-CF₃,6-CF.3	Me	5'-MeO, 6'-MeO	KeO	in, p. 154-158°C
275	(X-8)	3-CF3, 6-CF3	Me	5'-MeO, 6'-MeO	Meo
276	(X-8)	3-CFa, 5-Me,6-CF_:,	Me	5'-MeO, 6’-MeO	MeO
277	(X-8)	3-CF₃,5-Et, 6-CF₃	Me	5'-MeO, 6'-MeO	MeO
278	(X-8)	3-CFj, 5-Allyl,6-CF3	Me	5'-MeO, 6'-MeO	Meo
279	(X-8 )	3-CFj, 5-n-Propyl,6-CF3	Me	5'-MeO, 6'-MeO	MeO
280	(X-8)	3-CF₃,5-Propargyl,6-CF3	Me	5'-MeO, 6'-MeO	MeO
281	(X-8)	2-Cl,3-CF₃,5-e?3, 5-Cl	Me	5'-MeO, 6'-Meo	MeO	.
282	(X-8)	2-Cl,3-CFj, 5~CF₃	Me	5'-MeO, 6'-MeO	Meo

Table 36

No.	Formula	(X)n	R¹	(r²)_p	R³	Physical properties
283	(X-8)	3-CF₃,5-CF₃	Me	5'-MeO, 6'-MeO	MeO
284	(X-9)	3-Cl,5-Cl,6-C1	Me	5'-MeO, 6'-MeO	MeO	m.p. 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	m.p. 114-117°C

Cd

The benzoylpyr.idine derivative represented by the formula (I) or its salt is useful as an active ingredient fox a fungicide, particularly as an active ingredient for an agricultural and horticultural fungicide. As the agricultural and horticultural fungicide, it is effective fcr controlling diseases such as blast, brown spot or sheath blight of rice (Oryza sativa); powdery mildew, scab, rust, snow mold, loose smut, eyespot, leaf spot or glume blotch of barley (Hordeum vulgare); melanose or scab of citrus (Citrus)? blossom blight, powdery mildew, Altenaria leaf spot, or scab of apple (Malus puicila) ; scab or black spot of pear (Pyrus serotina, Pyrus ussuriensis, gyrus communis) ; brown rot, scab or Fomitopsis rot of peach (Prunus persica); Anthracnose, ripe rot, powdery mildew or downy mildew of grape (Vitis vinifera); anthracnose or circular leaf spot of Japanese persimmon (Diospyros kaki); anthracnose, powdery mildew, gummy stem blight or downy mildew of cucurbit (Cucumis meio); early blight, leaf mold or late blight of tomato (Lycopersicon esculentum) ; leaf blight of cress (Brassica sp.. , Raphanus sp., etc); early blight or late blight of potato (Solanum tuberosum); powdery mildew of strawberry (Fragaria chiioensis); gray mold, or stem rot of various crops, it shows an excellent controlling effect particularly on powdery mildew of barley and vegetables and rice blast. Further, it is also effective for controlling soil-borne diseases caused by phytopathogenic fungi such as

Fusarium, Pythium, Rhizoctonia, Verticillium and Plasmodiophora.

The compound of the present invention may be used in combination with an agricultural adjuvant to formulate various preparations of the fungicide containing the compound, such as a dust, granules, a granular wettable powder, a wettable powder, an aqueous suspension, an oil suspension, a water soluble powder, an emulsifiable concentrate, an aqueous solution, a paste, an aerosol or io a microdose dusting powder. The compound of the present invention may be formed into any preparation which is usually used in the agricultural and horticultural field so long as the purpose of the present invention is met. The adjuvant to be used for preparation may, for example, be a solid carrier such as diatomaceous earth, hydrated lime, calcium carbonate, talc, white carbon, kaolin, bentonite, a mixture of kaolinite and sericite, clay, sodium carbonate, sodium bicarbonate, glauber's salt, zeolite or starch; a solvent such as water, toluene, xylene, solvent naphtha, dioxane, acetone, isophorone, methyl isobutyl ketone, chlorobenzene, cyclohexane, dimethylsulfoxide, dimethylformamide, dimethylacetamide, N-methyl-2-pyrrolidone or an alcohol; an anionic surfactant or spreading agent such as a fatty acid salt, a benzoate, an alkyl sulfosuccinate, a dialkyl sulfosuccinate, a polycarboxylate, an alkyl sulfuric ester salt, an alkyl sulfate, an alkyl aryl sulfate, an

CP

CM

O

alkyl diglycol ether sulfate, an alcohol sulfuric ester salt, an alkyl sulfonate, an alkyl aryl sulfonate, an aryl sulfonate, a lignin sulfonate, an alkyl diphenyl ether disulfonate, a polystyrene sulfonate, an alkyl phosphoric ester salt, an alkyl aryl phosphate, a styryl aryl phosphate, a polyoxyethylene alkyl ether sulfuric ester salt, a polyoxyethylene alkyl aryl ether sulfate, a polyoxyethylene alkyl, aryl ether sulfuric ester salt, a polyoxyethylene alkyl ether phosphate, a polyoxyethylene ' A alkyl aryl phosphoric ester salt or a salt of e ,_teS r-·.,.. naphthalene sulfonic acid formalin condensate; a non·.

ionic surfactant or spreading agent such as a sorbitan fatty acid ester, a glycerol fatty acid ester, a. fatty acid polyglyceride, a fatty acid alcohol polyglycol 3 ether, an acetylene glycol, an acetylene alcohol, an m fcr oxyalkylene block polymer, a polyoxyethylene alkyl ether, *· a polyoxyethylene alkyl aryl ether, a polyoxyethylene styryl aryl ether, a polyoxyethylene glycol alkyl ether, a polyoxyethylene fatty acid ester, a polyoxyethylene sorbitan fatty acid ester, a polyoxyethylene glycerol fatty acid ester, a polyoxyethylene hardened caster oil or a polyoxypropylene fatty acid ester; vegetable oil or mineral oil such as olive oil, kapok oil, caster oil, palm oil, camellia oxi. coconut-oil, sesame oil, corn oil, rice bran oil, peanut oil, cotton oil, soy bean oil, rape oil, linseed oil, tung oil or liquid paraffin. A known adjuvant may be selected from adjuvants which are known in the agricultural and horticultural field within a range of not departing from the object of the present invention. Further, an adjuvant which is usually used may also be employed, such as a bulking agent, a thickener, an anti-settling agent, a freeze proofing agent, a dispersion stabilizer, a crop injury-reducing agent or a mildewproofing agent. The blending proportion of the compound of the present invention to the adjuvant is generally from 0.005:99.995 to 95:5, preferably from io 0.2:99.8 to 90:10. These formulations can be practically used either as they are or after they are diluted with a r·.diluent such as water to predetermined concentrations and _Λa spreading agent is added thereto as the case requires.

CX.

The concentration of the compound of the present invention varies depending upon the crop plant as the g object, the way of application, the form of preparation £*><

or the dose, and hence cannot be generically determined. However, in the case of foliage treatment, the concentration of the compound as the active ingredient is generally from 0.1 to 10,000 ppm, preferably from 1 to 2,000 ppm. In the case of soil treatment, it is generally from 10 to 100,000 g/ha, preferably from 200 to 20,000 g/ha.

The preparation fungicide containing the compound of the present invention or a diluted product thereof can be applied by an application method which is commonly used, such as spreading (spreading, spraying, misting, at.omiz2.ng, grain diffusing or application on water) , soil application (such as mixing or irrigation) or surface application (such as coating, dust coating or covering). Further, it may be applied also by so-called ultra low volume. By this method, the preparation can contain 100% oi the active ingredient.

The fungicide of the present invention may be mixed or used together with e.g. another agricultural chemical such as an insecticide, a miticide, a nematicide, a fungicide, an antiviral agent, an attractant, an herbicide or a plant growth regulator. In such a case, a still more excellent effect may be obtained in some cases .

Examples of the active ingredient compound (generic name; including compounds which are under application) cf the insecticide, miticide or nematicide i.e. a pesticide of the above other agricultural chemicals, include organic phosphate type compounds such as Profenofos, Dichlorvos, Fenamiphos, Fenitrothion, EPN, Diazinon,

Chlorpyrifos-methyl, Acephate, Prothiofos, Fosthiazate, Phosphocarb, Cadusafos and Dislufoton;

carbamate type compounds such as Carbaryl, Propoxux, Aldicarb, Carbofuran, Thiodicarb, Methomyl, Oxamyl,

Ethiofencarb, Pirimicarb, Fenobucarb, Carbosulfan and

Benfuracarb;

nelicetoxin derivatives such as Cartap and Thiocyclam;

pP

IBP

WB organic chlorine type compounds such as Dicofol and Tetradifon;

organic metal type compounds such as Fenbutatin Oxide;

pyrethroid type compounds such as Fenvalerate,

Permethrin, Cypermethrin, Deltamethrin, Cyhalothrin, Tefluthrin, Ethofenprox and Flufenprox;

benzoyl urea type compounds such as Diflubenzuron, Chlorfluazuron, Teflubenzuron and Flufenoxuron;

juvenile hormone-like compounds such as Methoprene;

pyridazinone type compounds such as Pyridaben; pyrazole type compounds such as Fenpyroximate,

Fipronil, Tebufenpyrad, Ethiprole, Tolefenpyrad and Acetoprole;

neonicotinoides such as Imidacloprid, Nitenpyram,

Acetamiprid, Thiacloprid, Thiamethoxam, Clothianidin, Nidinotefuran and Dinotefuran;

hydrazine type compounds such as Tebufenozide, Methoxyfenozide and Chromafenozide;

pyridine type compounds such as Pyridaryl and

Flonicamid;

tetronic acid type compounds such as Spirodiclofen; strobilurin type compounds such as Fluacrypyrin; dinitro type compounds, organosulfur compounds, urea type compounds, triazine type compounds, hydrozone type compounds and other compounds such as Buprofezin,

Hexythiazox, Amitraz, Chlordimeform, Silafluofen, tet*

O

Triazamate, Fymetrozine, Pyrimidifen, Chlorfenapyr, Indoxacarb, Acequinocyl, Etoxazole, Cyromazine and 1,3dichloropropene; AKD-1022 and IKA-2000. Further, the fungicide of the present invention may also be mixed or used together with a microbial pesticide such as a BT agent or an insect pathogenic virus agent or an antibiotic such as Avermectin, Milbemycin, Spinosad or

Emamectin Benzoate,

Of these other agricultural chemicals, examples of the active ingredient compounds of the fungicides (generic name; including compounds which are under application) include pyrimidinamine type compounds such as Mepanipyrim, Pyrimethanil and Cyprodinil, pyridinamine type compound such as Fluazinam;

azole type compounds such as Triadimefon,

Bitertanol, Triflumizole, Etaconazole, Propiconazole, Penconazole, Flusilazole, Myclobutan.il, Cyproconazole, Terbuconazole, fiexaconazole, Furconazole-cis, Prochloraz, Metconazole, Epoxiconazole, Tetraconazole, Oxpoconazole fumarate and Sipconazole;

quinoxaline type compounds such as Quinomethionate; dithiocarbamate type compounds such as Maneb, zineh,

Mancozeb, Polycarbamate, Metiram and Propineb;

organic chlorine type compounds such as Fthalide,

Chlorothalonil and Quintozene;

imidazole type compounds such as Benomyl, Thiophanate-Methyl, Carbendazim and Cyazofainid;

ace it thJ bw fe cyanoacetamide type compounds such as Cymoxanil; phenylamide type compounds such as Metalaxyl,

Metalaxyl M, Oxadixyl, Ofurace, Benalaxyl, Furalaxyl and Cyprofuram;

sulfenic acid type compounds such as Dichlofluanid; copper type compounds such as Cupric hydroxide and

Oxine Copper;

isoxazole type compounds such as Hydroxyisoxazole; organophosphorus compounds such as Fosetyl-Al,

Tolcofos-Methyl, S-benzyl O, Odiisopropylphosphorothioate, O-ethyl S,Sdiphenylphosphorodithioate and aluminum ethyl hydrogen phosphonate;

N-halogenothioalkyl type compounds such as Captan, Captafol and Folpet;

dicarboxyimide type compounds such as Procymidone, Iprodione and Vinclozolin;

benzanilide type compounds such as Flutolanil, Mepronil and Zoxamid;

piperazine type compounds such as Triforine; pyridine type compounds such as Pyrifenox; carbionol type compounds such as Fenarimol and

Flutriafol;

piperidine type compounds such as Fenpropidine; morpholine type compounds such as Fenpropimorph; organotin type compounds such as Fentin Hydroxide and Fentin Acetate;

iv

O

Cv c··

I €

<

urea type compounds such as Pencycuron; cinnamic acid type compounds such as Dimethomorph; phenyl carbamate type compounds such as

D i e t ho f enc ar b;

cyanopyrrole type compounds such as Pludioxon.il and

Fenpiclonil;

strobilurin type compounds such as Azoxystrobin, Kresoxim-Methyl, Metominofen, Triflouxystrobin . Picoxystrobin and Pyraclostrobin: (BAS 5OOF);

oxazolidinone type, compounds such as Famoxadone; thiazole carboxamide type compounds such as Ethaboxam;

silyl amide type compounds such as Silthiopham; aminoacid amidecarhamate type compounds such as iprovalicarb and Benthiavalicarb; Imidazolidine type compounds such as fenamidone; hydroxyanilide type compounds such as Fenhexamid; benzene sulfonamide type compounds such as Flusulfamid; oxime ether type compounds such as Cyflufenamid; phenoxyamide type compounds such as Fenoxanil; triazole type compounds such as Simeconazole;

anthraquinone type compounds; crotonic acid type compounds; antibiotics and other compounds such as Isoprothiolane, Tricyclazole, Pyroquilon, Diclomezine, Pro, benazole, Quinoxyfen, Propamocarb Hydrochloride, Spiroxamine, Chloropicrin, Dazomet and Metam-sodium; and

BJIi-993, BJL-994, BAS-510, BAS-505, MTF-753 and u'IBF-307. Now, Test Examples of the agricultural and

1'lb horticultural fungicides of the present invention will be described below. However, the present invention is by no means restricted thereto. In each test, the controlling index was determined on the basis of the following standards.

[Controlling index];[Degree of disease outbreak:Visual observation] : No lesions nor sporogony recognizable 4 : Area of lesions, number of lesions or area of sporogony is less than 10% of non-treated plot : Area of lesions, number of lesions or area of sporogony is less than 40% of non-treated plot : Area of lesions, number of lesions or area of sporogony is less than 70% of non-treated plot : Area of lesions, number of lesions or area of sporogony is at least 70% of non-treated plot

TEST EXAMPLE 1

F'

Tests on preventive effect against wheat powdery mildew

Wheat (cultivar: Norin-61-go) was cultivated in a polyethylene pot having a diameter of 7.5 cm, and when the wheat reached a one and a half-leaf stage, the wheat was sprayed with 10 mfi of a drug solution having a predetermined concentration of the compound of the present invention by a spray gun. After the drug solution dried, the wheat was inoculated by spreading with conidiospore of fungi of powdery mildew, and the wheat was kept in a thermostatic chamber at 20°C. From 6 to 8 days after the inoculation, the area of sporogony was examined to determine the controlling index, in accordance with the above evaluation standards. As a result, of the above compounds, compounds Nos. 1, 2, 8, 47, 58, 61, 62, 69, 73, 76, 77, 78, 83, 87, 91, 107, 110, 112, 1.14, 117, US., 138, 250, 262 and 274 showed effects with a controlling index of 4 or above at a concentration

of 500 ppm.,	and the compounds Nos. 3, 4, 5,	6,	7, 9,	, 10,
11, 13, 14,	18, 19, 23, 27, 30, 31, 32, 33,	34,	. .3 5 ,	3 6,
38, 40, 41,	43, 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,	1.23 ,
124,	133,	136, 142,	186,	187,	188,	189,	190, 19.1,	1.92,
193,	194,	199, 200,	210,	211,	213,	228,	243, 245,	249,
252,	254,	272, 287,.	288,	289,	290,	291	and 292 showed

effects with a controlling index of 4 or above at a concentration of 125 ppm.

TEST EXAMPLE 2

Test on preventive effect against rice blast

Rice (cultivar; Nihonbare) was calculated in. a polyethylene pot having a diameter of 7.5 cm, esnd when the rice reached a one and a half-leaf stage, the rice was sprayed with 10 mfi- of a drug solution having a predetermined concentration of the compound of the present invention by a spray gun. After the drug solution dried, the rice was sprayed and inoculated with a. conidiospore suspension of fungi of rice blast, and the rice was kept in an inoculation box at 20°C fox 24 hours, and then kept in a thermostatic chamber at 20°C. From 6 to 11 days after the inoculation, the number of lesions was examined to determine the controlling index in accordance with the above evaluation standards. As a result, of the above compounds, the compounds Nos. 31,

56, 76, 90, 103 and 136 showed effects with a controlling index of 4 or above at a concentration of 500 ppm, and the compounds Nos. 50, 74, 75 and 102 showed effects with a controlling index of 4 or above at a concentration of 125 ppm.

TEST EXAMPLE 3

Test on preventive effect against eggplant powdery mildew

Eggplant (cultivar: Senryo-2-go) was cultivated in a polyethylene pot having a diameter of 7.5 cm, and when the eggplant reached a two-leaf stage, the eggplant was sprayed with 10 mfi of a drug solution having a predetermined concentration of the compound of the present invention by a spray gun. After the drug solution dried, the eggplant was inoculated by spreading with conidiospore of fungi of eggplant powdery mildew, and the eggplant was kept in a thermostatic chamber at 20°C. 16 days after the inoculation, the area of sporogony was examined to determine the controlling index in accordance with the above evaluation standards. As a result, of the above compounds, compounds Nos. 1, 3, 5,

7, 92, 101 and 103 showed effects with a controlling index of 4 or above at a concentration of 500 ppm, and t

»- the compounds Nos. .9, 11, 55, 90 and 102 showed effects with a controlling index of 4 or above at a concentration of 125 ppm.

TEST EXAMPLE 4 ⁵ Test on preventive effect against cucumber powdery mildew

Cucumber (cultivar: Suyo) was cultivated in a polyethylene pot having a diameter of 7.5 cm, and when the cucumber reached one and a half-leaf stage, the cucumber was sprayed with a 10 mfl of a drug solution io having a predetermined concentration of the compound of the present invention by a spray gun. After the drug solution dried, the cucumber was sprayed and inoculated with a conidiospore suspension of fungi of powdery mildew, and the cucumber was kept in a thermostatic is chamber at 20 °C. From 7 to 11 days after the inoculation, the area of sporogony was examined to determine the controlling index in accordance with the above evaluation standards. As a result, of the above compounds, the compound No. 98 showed effects with a controlling index of i or above at a concentration of 500 ppm, and compounds Nos. 1, 5, 7, 9, 55, 74, 90, 92, 93, 102, 103, 123 and 124 showed effects with a controlling index of 4 or above at a concentration of 1.25 ppm.

Now, Formulation Examples of the compounds of the present invention will be described below. However, the formulation dose, the dosage form or the like is by no means restricted to the following Examples.

Di •V.

th'ft-o·

FORMULATION EXAMPLE 1 (1) Compound of the present invention parts by weight (2) Clay 72 parts by weight (3) Sodium lignin sulfonate 8 parts by weight

The above components are uniformly mixed to obtain a wettable powder.

FORMULATION EXAMPLE 2 (1) Compound of the present invention io 5 parts by weight (2) Talc 95 parts by weight

The above components are uniformly mixed to obtain a dust.

FORMULATION EXAMPLE 3 (1) Compound of the present invention parts by weight (2) N,N'-dimethylacetamide 20 parts by weight (3) Polyoxyethylene alkyl phenyl ether parts by weight (4) Xylene 50 parts by weight

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

FORMULATION EXAMPLE 4 (1) Clay 68 parts by weight (2) Sodium lignin sulfonate 2 parts by weight (3) Polyoxyethylene alkyl aryl sulfate parts by weight

0 (4) Fine silica. 25 parts by weight

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

FORMULATION EXAMPLE 5 (1) Compound of the present invention parts fay weight (2) Oxylated polyalkylphenyl phosphatetriethanolamine 2 parts by weight.

io (3) Silicone 0.2 part by weight (4( Water 47.8 parts by weight

The above components are uniformly mixed and pulverized to obtain a stock solution, and (5) Sodium polycarboxylate 5 parts by weight (6) Anhydrous sodium sulfate 42.8 parts by weight are further added thereto, followed by uniform mixing, granulation and drying to obtain a granular wettable powder .

y^:x iff/

VG <y

I ifl

FORMULATION EXAMPLE b (1) Compound of the present invention parts by weight (2) Polyoxyethylene octylphenyl ether part by weight (3) Phosphate of polyoxyethylene

0.1 part by weight (4) Particulate calcium carbonate

93.9 parts .by weight

101

The above components (1) to (3) are preliminarily mixed uniformly and diluted with a proper amount of acetone, the diluted mixture is sprayed on the component (4), and acetone is removed to obtain granules. FORMULATION EXAMPLE 7 (1) Compound of the present invention

2.5 parts by weight (2) N-methyl-2-pyrrolidone 2.5 parts by weight (3) Soybean oil 95.0 parts by weight

The above components are uniformly mixed and dissolved to obtain an ultra low volume formulation.

FORMULATION EXAMPLE 8 (1) Compound of the present invention parts by weight (2) Oxylated polyalkylphenol phosphate cm

triethanolamine	2 parts by weight
(3) Silicone	0.2 part by weight
(4) Xanthan gum	0.1 part by weight
(5) Ethylene glycol	5 parts by weight
(6) Water	72.7 parts by weight
The above components	are uniformly mixed and

pulverized to obtain an aqueous suspension.

INDUSTRIAL APPLICABILITY

As mentioned above, the benzoylpyridine derivative 25 represented by the formula (I) or its salt has excellent effects as an active ingredient of a fungicide.

Claims

1 A fungicide which contains a benzoylpyridine derivative represented by the formula (I) or its sait:
wherein X is a halogen atom, a nitro group, a substitutable alkoxy group, a substitutable aryloxy group, io a substitutable cycioalkoxy group, a hydroxyl group, a substitutable hydrocarbon group, a substitutable alkylthio group, a cyano group, a carboxyl group which may be esterified or amidated, or a substitutable amino group; n is 1, 2, 3 or 4; R¹ is a substitutable alkyl

15 group,- R² is a substitutable alkyl group, a substitutable alkoxy group, a substitutable aryloxy group, a substitutable cycioalkoxy group or a hydroxyl group,· and at is 1, 2, 3 or 4, provided that when m is at least 2, R²may contain an oxygen atom to form a condensed ring

20 (excluding a case where the pyridine ring is substituted by a benzoyl group at the 2-position; the pyridine ring is substituted by an alkoxy group, a hydroxyl group ox a benzyloxy group at the 3-position; and n is 1, m .is 1 or 2) as an active ingredient.

25 2 . The benzoylpyridine derivative or its salt according to claim 1 as an active ingredient of a fungicide, wherein X is a halogen atom, a nitro group, a substitutable alkoxy group, a substitutable aryloxy group,

Ϊ»'ϊ a

.

Λ * h .

103 a substitutable cycloalkoxy group, a hydroxyl group, a substitutable hydrocarbon group, a substitutable alkylthio group, a cyano group or a substitutable amino group.

5 3 . The benzoylpyridine derivative or its salt according to claim 1 as an active ingredient of a fungicide, wherein m is 2, 3 or 4.

4. The benzoylpyridine derivative or its salt according to claim 1 as an active ingredient of a fungicide, wherein R¹ is an alkyl group, and R² is an alkyl group, an alkoxy group or a hydroxyl group, io 5. A benzoylpyridine derivative or its salt, which is represented by the formula (I'):

Cm

O wherein X, n and R¹ are as defined in Claim 1, R²' is a

4 .

substitutable alkyl group, a substitutable alkoxy group, * 15 a substitutable aryloxy group, a substitutable cycloalkoxy group or a hydroxyl group, p is 1, 2 or 3, and R²'' is a substitutable alkoxy group or a hydroxyl group, provided that at least two of R²' and R² may contain an oxygen atom to form a condensed ring

20 (excluding (1, a case where the pyridine ring is substituted by a benzoyl group at the 2-position; the pyridine ring is substituted by an alkoxy group, a hydroxyl group or a benzyloxy group at the 3-position; and n is 1, p is 1_; (2) a case where the pyridine ring is substituted by a chlorine atom or a bromide atom at-ttre-a-position, and n is 1; and (3) a case where the pyridine ring is substituted by a benzoyl'grou^aTTTrft-a-jygsition, and the pyridine ring is substituted by a hydrogen atom at the 5-postion) ____

104

6. The benzoylpyridine derivative or its salt according to Claim. 5, which is represented by the formula. (I''):

wherein X is a halogen atom, a nitro group, a 5 substitutable alkoxy group, a substitutable aryloxy group, a substitutable cycloalkoxy group, a substitutable hydrocarbon group, a substitutable alkylthio group, a cyano group, a carboxyl group which may be esterified or amidated, or a substitutable amino group; n is 1, 2, 3 or

10 4; R¹ is an alkyl group; R²' is a substitutable alkyl group, a substitutable alkoxy group, a substitutable aryloxy group or a substitutable cycloalkoxy group, p is 1, 2 or 3, and each of R² and R²” is a substitutable alkoxy group.

15 7, The. benzoylpyridine derivative or its salt according to Claim 5, which is represented by the formula (I') ;

v.

κα

i.

•ae, •IM S A <

wherein X is a halogen atom, a substitutable alkoxy group, an alkyl group, a CF₃ group or an alkylthio group; n is 1,

105

2, 3 or 4; R¹ is an alkyl group; R²* is a substitutable alkyl group, a substitutable alkoxy group or a substitutable cycloalkoxy group; p is 1, 2 or 3; and each of R² and R²' is a substitutable alkoxy group.

5 8. The benzoylpyridine derivative or its salt according to Claim 5, which is represented by the formula (I,:

wherein X is a halogen atom, an alkoxy group, an alkyl group, a CF₃ group or an alkylthio group; n is 1, 2 or 3;

10 R¹ is an alkyl group; R²' is an alkoxy group; p is 1, 2 or 3, and each of R² and R²' is an alkoxy group.

9. The benzoylpyridine derivative or its salt according to Claim 8, which is represented by the formula (I'''' ') :

«0 ©

CM ©

wherein B is -CX⁴= when A is -N=; B is -N= when A is -CH=; each of X¹ and X² which are independent of each other, is a halogen atom, an alkoxy group, an alkyl group,

106 a CF3 group or an alkylthio group; X? is a halogen atom, an alkoxy group, an alkyl group. £. CF₃group or an alkylthio group; X⁴ is a hydrogen atom, a halogen atom, an alkoxy group, an alkyl group, a C?₃

5 group or an alkylthio group; R¹ is an alkyl group; R²' is an alkoxy group; p is 1, 2 or 3; and each of R² ’ and R²’ is an alkoxy group.

10, A fungicide which contains the benzoylpyridine derivative represented by the formula (I') or its salt as

10 defined in Claim 5 as an active ingredient.

11- A process for producing a benzoylpyridine derivative represented by the formula (I) or its salt:

o «3 il {wherein X is a halogen atom, a nitro group, a substitutable alkoxy group, a substitutable aryloxy group, a substitutable cycloalkoxy group, a hydroxyl group, a substitutable hydrocarbon group, a substitutable alkylthio group, a cyano group, a carboxyl group which may be esterified or amidated, or a substitutable amino grono; n is 1, 2, 3 0

Ph is a substitutable aihoi

107 group; R²' is a substitutable alkyl group, a substitutable alkoxy group, a substitutable aryloxy group, a substitutable cycloalkoxy group or a hydroxyl group; and p is 1, 2 or 3; and R² is a substitutable alkoxy group or hydroxyl group, provided that at least two R² and R² may contain an oxygen atom to form a condensed ring (excluding (1) a case where the pyridine ring is substituted by a benzoyl group at the 2-position; the pyridine ring is substituted by an alkoxy group, a hydroxyl group or a benzyloxy group at the 3-position; and n is 1, p is 1 or (2) a case where the pyridine ring is substituted by a chlorine atom or a bromide atom at the 2-position, and n is 1; and (3) a case where the pyridine ring is substituted by a benzoyl group at the 3-position, and the pyridine ring is substituted by a hydrogen atom at the 5-postion)
2)}, which process comprises reacting a substituted benzaldehyde represented by the formula (VI-1):

e

J****!

CM €>

(wherein R¹, R², R² and p are as defined above) and a metal salt of a substituted pyridine derivative represented by the formula (VII-1):

(wherein X is as defined above, and Z is a metal atom or a composite salt thereof) to produce phenylpyridyl methanol represented by the formula (X):

108 proviso as in formula (ί)), and oxidizing it.

12 . A process for producing a benzoylpyridine derivative .represented by the formula (I) or its salt:

{wherein X is a halogen atom, a nitro group, a substitutable alkoxy group, a substitutable aryloxy group, a substitutable cycloalkoxy group, a io substitutable hydrocarbon group, a substitutable alkylthio group, a cyano group, a carboxyl group which may be esterified ox amidated, or a substitutable amino group; n is 1, 2, 3 or 4; R¹ is a substitutable alkyl group; R² is a substitutable alkyl group, a substitutable

15 alkoxy group, a substicutable aryloxy group, a substitutable cycloalkoxy group or a hydroxyl group; and p is 1, 2 or 3; and R²’ is a substitutable alkoxyl group or a hydroxyl group; provided that at least two of R² and R² may contain an oxygen atom to form a condensed ring may contain an oxygen atom to form a condensed ring (excluding (11 a case where the pyridine ring ic subsu aaai %

'W i

L

109 by a benzoyl group at the 2-position; the pyridine ring is substituted by an alkoxy group, or a benzyloxy group at the 3-position? and n is 1, p is 1 (2) a case where the pyridine ring is substituted by a chlorine atom or a ₅ bromide atom at the 2-position, and n is 1; and (3) a case where the pyridine ring is substituted by a benzoyl group at the 3-position, and the pyridine ring is substituted by a hydrogen atom at the 5-postion) , vzhich process comprises reacting a metal salt of a substituted benzene derivative represented by the formula (VI-2):

(wherein rSR², R^r and p are as defined above, and Z is a metal atom or a composite salt thereof) and a substituted pyridyl aldehyde represented by the formula (VII-2):

(wherein X is as defined above) to produce phenylpyridyl methanol represented by the formula (X) :

«8.

C* <\s o

·***, <.

(wherein X, n, p₃ R¹, r²', _anc| pz- are as defined above with a proviso as in formula (ij ), and oxidizing it.

110

13 . The phenylpyridyl methanol which is represented by the formula (X'')

FV

QH =>.(R²),

F_aC“

X

N Wn-i p-i

R²” whereixi x is a halogen atom, a nitro group, a substitutable alkoxy group, a substitutable aryloxy group, a substitutable cycloalkoxy group, a substitutable hydrocarbon group, a substitutable alkylthio group,, a cyano group, a carboxyl group which may be esterified or amidated, or a substitutable amino group; n is 1,, 2, 3 or 4; R¹ is an alkyl group; R²' is a substitutable alkyl group, a substitutable alkoxy group, a substitutable arylexy group or a substitutable cycloalkoxy group, ρ is 1, 2 or 3, and each of R² and R²' is a substitutable aIkoxy group .

14 . The phenylpyridyl methanol represented by the formula (X' ' ');

₃1 cc

OH ,F!pl ,

-R

2“ v

'hf Mn

V*' wherein Σ is a halogen atom, a substitutable alkoxy group, an alkyl group, a CF₃ group or an alkylthio group,- n is 1, 2, .3 or 4; R¹ is an alkyl group; R²' is a subs ti tub-ible alkyl group, a substitutable alkoxy group or a

111 substitutable cycloalkoxy group; p is 1, 2 or 3; and each of R²” and R²' is a substitutable alkoxy group.

15. The phenyIpyridyl methanol according to Claim 14 , which is represented by the formula (X''''):

wherein X is a halogen atom, an alkoxy group, an alkyl group, a CF₃ group or an alkylthio group,· n is 1, 2 or 3; R¹ is an alkyl group; R²' is an alkoxy group; p is 1, 2 or 3; and each of R² and R²”' is an alkoxy group.

10 16 . The phenyIpyridyl methanol according to Claim 15 , which is represented by the formula (X' ' ' ' :

ifn·,

Z-J c««**

IP wherein B is -CX⁴- when A is -N=; B is -N= when A is -CH=? each of X¹ and X² which are independent of each

15 other, is a halogen atom, an alkoxy group, an alkyl group, a CP₃ group or an alkylthio group; X³ is a hydrogen atom, a halogen atom, an alkoxy group, an alkyl group, a CF3 group or an alkylthio group; X⁴ is a hydrogen atom, a halogen atom, an alkoxy group, an alkyl group, a CF3 grouo or an alkylthio group; R¹ is an alkyl group; R²' is

FISHER,₂CORM/\CK & BOTHA an alkoxy group; p is 1, 2 or 3; and the Applicant i, Dated this - day of is an alkoxy group. ⁷