Title of Invention	BENZOYLPYRIDINE DERIVATIVE OR ITS SALT, FUNGICIDE CONTAINING IT AS AN ACTIVE INGREDIENT, ITS PRODUCTION PROCESS AND INTERMEDIATE FOR PRODUCING IT
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 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.

Title of Invention

BENZOYLPYRIDINE DERIVATIVE OR ITS SALT, FUNGICIDE CONTAINING IT AS AN ACTIVE INGREDIENT, ITS PRODUCTION PROCESS AND INTERMEDIATE FOR PRODUCING IT

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 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.

Full Text	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. 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 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) or its salt: wherein X is a fluorine atom, a chlorine atom, a bromine atom, a iodine atom, a nitro group, an Ci-o alkoxy group which may be substituted by a C6-10 aryl, a C6-10 aryloxy, a hydroxyl, a nitro, a nitroxy, a halogen, a C1-4 haloalkoxy, a C5-6 cycloalkyl, amino, a C1-6 alkylthio or a cyano; a naphthyloxy group which may be substituted by a halogen, a C1-6 alkyl or a hydroxyL' a phenoxy group which may be substituted by a halogen, a C1-6 alkyl or a hydroxyl; a C6-10 cycloalkoxy group which may be substituted by a halogen ox a hydroxyL" a hydroxyl group; a hydrocarbon group selected from a C1-6 alkyl, a C2-6 aBcenyl group, a C2-6 alkynyl group, a C5-6 cydoalkyl group, and a C5-10 aryl group, which groups may be substituted by a C5-10 aryl, a C5-10 aryloxy, a hydroxyl, anitro, anitroxy, a halogen, a C1-4 haloalkoxy, a Ca-a cycloaliyl, a C1-0 alkylthio or acyano; a C1-0 alkylthio group which may be substituted by a C6-10 aryl, a C6-10 aryloxy, a hydroxyl, anitro, anitroxy, a halogen, a C1-4 haloalkoxy or acyano; a eyano group; a C1-6 alkoxycarbonyl group; a nitroxy C1-4 alkoxyaminocarbonyl group! a phenyl C1-4 alkoxycarbonyl group; a carbamoyl group! a mono C1-6 alkylaminocarbonyl group; a di C1-6 alkylaminocarbonyl group; a nitroxy C1-4 alkylaminocarbonyl group; a phenyl C1-4 alkylaminocarbonyl group; a Ca-6 cycloalkylamicnocarbonyl group; a moxpbolinocarbonyl group! a piperidinocarbonyl group; a pyrrolidmocarbojiyl group; a tbiomorpnolinocarbonyl group; an aminocarbonyl group; an amino group, a mono C1-4 alkylamino group or a di C1-4 alkylamino group; n is 1, 2, 3 or 4' R1 is a C1-6 alkyl group; R2'is a C1-6 alkyl group, a C1-6 alkoxy group, p ia 1, 2 or 3, and R2" is a C1-4 alkoxy group with the proviso that (l) the pyridine ring is not substituted by the benzoyl group at the 2-position; the pyridine ring is substituted, by a C1-6 alkoxy group, a hydroxyl group or a benzyloxy group at the 3-position>' and n is 1, p is 1 and that (2) the pyridine ring is not substituted by a chlorine atom or bromine atom at the 2-position and n is 1. Preferably the benzoylpyridine derivative or its salt is represented by the formula (I") wherein X is a halogen atom, a nitro group, a C1-6 alkoxy group which may be substituted by a C1-6 aryl, a C1-6 aryloxy, a hydroxyl, anitro, a nitroxy, a halogen, a C1-4 haloalkoxy, a C1-6 cydoalkyl, an amino, a C1-6 alkylthio or a cyanol a naphthyloxy group which may be substituted by a Halogen, a hydroxyl; a phenoxy group which, may be substituted by a halogen,. a C1-6 alkyl or a hydxoxyL a C1-6 cycloalkoxy group which may be substituted by a halogen or a hydroxyl; a hydrocarbon, group selected from a C1-6 alkyl, a C2-6 alkenyl group, a C2-6 alkynyl group, a Ca-6 cydoalkyl group, and a C5-10 aryl group, which groups may be substituted by a C6-10 aryl, a C6-10 aryloxy, a hydroxyl, a nitro, a nitroxy, a halogen, a C1-4 haloalkoxy, a C5-6 cycloaliyl, an amiiio, a C1-6 alkylthio or a cyano! a C1-6 alkylthio group which may be substituted by a C5-10 aryl, a C5-10 aryloxy, a hydroxyl, a nitro, a nitroxy, a halogen, a C1-6 haloalkoxy or a cyano; a cyano group, a C1-6 alkoxycarbonyl group, a nitroxy C1-4 alkoxyaminocarbonyl group, a phenyl C1-4 alkoxycarbonyl group, a carbamoyl group, a mono C1-6 alkylaminocafbonyl group, a di C1-6 alkylaminocarborLyl group, a nitroxy C1-4 alkylaminocarbonyl group, a phenyl C1-4 alkylaminocarbonyl group, a C3-6 cycloalkylaminocarbonyl group, a morphoi i nncarbonyl group; a piperidinocarbonyl group; a pyrrolidinocarbonyl group; a thioinorpholinocarbonyl group; an aminocarbonyl group, an amino group, a mono C1-4 alkylamino group or a di C1-4 alkylamino group; n is 1, 2, 3 or 4; R1 is a C1-6 alkyl group! R2' is a C1-6 alkyl group or a C1-6 alkoxy group; p is 1, 2 or 3, and each of R2" and R2"1 is a C1-6 alkoxy group. More preferably the benzoylpyridine derivative or its salt is represented by the formula (I'') wherein X is a halogen atom, a C1-6 alkoxy group, a C1-6 alkyl group, a CF3 group or a Ci-c alkylthio group; n ia 1, 2, 3 or 4; R1s a Ci-g alkyl group; R2'is a C1-6 alkyl group or a C1-6 alkoxy group; p is 1, 2 or 3; and each of R2" and R2" is a C1-6 alkoxy group. More preferably the benzoylpyridine derivative or its salt is represented by the formula (I"") wnexein X is a. halogen atom, a C1-6 alkoxy group, a C1-6 alkyl group, a CFs group or a C1-4 aliylthio group; n is 1, 2 or 3; R1 is a C1-6 alkyl group; R2'is a C1-6 alkoxy group; p is 1, 2 or 8, and each of R2" and R2'' is a C1-6 alkoxy group. wherein B is -CX4= whenAis -N=; B is -N= whenAis -CH=; each, of X1 and X2 which are independent of each other, is a halogen atom, a C1-6 alkoxy group, a C1-6 alkyl group, a CPs group or a C1-6 alkylthio group! X3 is a hydrogen atom, a halogen atom, a C1-6 alkoxy group, a C1-6 alkyl group, a CFs group or a C1-6 alkylthio group ? X4 is a hydrogen atom, a halogen atom, a C1-6 alkoxy group, a C1-6 alkyl group, a CF3 group or a C1-6 alkylthio group, IVis a C1-6 alkyl group! R2" is a C1-6 alkoxy group; p is 1, 2 or 3; and each of R2" and R2" is a C1-6 alkoxy group . The benzoylpyridine derivative represented by the formula (I') or its salt for preventing I curing fungal diseases. The present invention also provides a process for producing a benzoylpyridine derivative represented by the formula (I') or its salt: wherein X, n and R1 are as defined in claim 1, R2' is a C1-6 aliyl group or a C1-6 alkoxy group, p is 1, 2 or 3, and R2" is a C1-6 alkoxy group with the proviso that (1) the pyridine ring is not substituted by the benzoyl group at the 2-position; the pyridine ring is substituted by a C1-6 alkoxy group, a hydroxyl group or a benzyloxy group at the 3-positionJ and n is 1, p is 1 and (2) that the pyridine ring is not substituted by a chlorine atom or bromine atom at the 2-position and n ia 1, which process comprises reacting a substituted benzaldehyde represented by the formula (VI-1'): (wherein R1, R2', R2" and p are as defined above) and a metal salt of a substituted pyridine derivative represented by the formula (VIM) - (wherein X is as defined above, and Z is a metal atom such as lithium, magnesium, zinc or copper, or a transition metal atom such as palladium or ruthemium or a composite salt thereof) to produce phenylpyridyl methanol represented by the formula (X1): (wherein X, n, p, R1, R2' and R2" are as defined above, with a proviso as in formula (I')), and oxidizing it. A preferred embodiment is a process for producing a benzoylpyridine derivative represented by the formula (I1) or its salt: wherein X, n and Rl are R2 is a C1-6 alkyl group or a C1-6 ajkoxy group, p is 1, 2 or 3, and R2 is a C1-6 alkoxy group with the proviso that (l) the pyridine ring is not substituted by the benzoyl group at the 2-position>' the pyridine ring is substituted by a C1-6 alkoxy .group, a hydroxyl group or a benzyloxy group at the 3-position; and n is 1, p is 1 and (2) that the pyridine ring is not substituted by a chlorine atom or bromine atom at the 2-position and n is 1, which process comprises reacting a metal salt of a substituted benzene derivative represented by the formula (VI-21)' (wherein Rl, R2", R2" and p are as defined above and Z is a metal atom such as lithium, magnesium, zinc or copper, or a transition metal atom such as palladium or ruthemium 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 (X1): (wherein X, n, p, R1 ,R2'and R2" are as defined above with a proviso as in formula (I')), and oxidizing it, 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, R2, n and m in the formulae are as defined above. One of the substituents represented by M1 in the formula (II) and M2 in the formula (III) is a cyano group, and the other is a 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 18 by the formula (III) to a condensation reaction to produce an imine compound represented by the formula (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 it. The metal atom represented by each of M1 and M2 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 M2 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 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 solvent thereof) at a reaction temperature of from -10 0 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 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, R2, 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 benzenesulfinate or sodium p-toluenesulfinate may be 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 triethylammonium 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 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 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 oxidizing agent such as manganese dioxide or chromic acid, a Swern oxidation method (dimethylsulfoxide + oxalyl chloride) or a ruthenium oxidation method (tetrapropylammonium perruthenate + N-methylmorpholine-N- oxide) and converted to a compound represented by the formula (I) Now, mode of carrying out Process 3 is described below. (1) A process for producing the compound represented by the formula (I), which comprises reacting a substituted benzaldehyde represented by the formula (VI- 1) : (wherein R1, R2 and m 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), 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): (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): (wherein X is as defined above), to produce phenylpyridyl 5 methanol represented by the formula (X), and oxidizing it. Here, the preferred modes of the phenylpyridyl methanol represented by the formula (X) which is an intermediate for production of the compound represented by the formula (I) are shown below. (1) Phenylpyridyl methanol represented by the formula (X'): 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 R2" 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 phenylpyridyl methanol according to the above item (1), which is represented by the formula (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 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 0 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 phenylpyridyl methanol according to the above item (5), which is represented by the formula 5 (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. (7) The phenylpyridyl methanol according to the above item (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 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 (I). Here, in the formula (I- a), E is an electrophilic reagent, and in the formula (I- b), Nu is a nucleophilic reagent. n' and n' are as defined for the above n. 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 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 (I- c) (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. 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 of 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- c) . Further, the reaction may be carried out in the presence of a base such as triethylamine or sodium hydrogen carbonate. Further, a known reduction reaction may be employed such as hydrogen transfer reaction (e.g. palladium carbon, ammonium formate as a hydrogen source, or sodium dihydrogen phosphate) or a metal reduction reaction (e.g. samarium diiodide). Now, specific Synthesis Examples of the benzoylpyridine derivative represented by the formula (I) and the intermediate for its production are described below (the compounds in Synthesis Examples are based on IUPAC nomenclature, and the substitution positions may be different from those shown in Tables as mentioned hereinafter, expediently). SYNTHESIS EXAMPLE 1 Synthesis of 3-(2,3,4-trimethoxy-6-methylbenzoyl)-2,6- dichloro-4-trifluoromethylpyridine (compound No. 3) (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 mfi (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 mfi of tetrahydrofuran was added thereto, followed by stirring for 1.5 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 6.2 g (yield 81%) of (2,3,4-trimethoxy-6- methylphenyl)(2,6-dichloro-4-trifluoromethyl-3- pyridyl)methanol (brown oily substance). (b) 14 g of manganese dioxide was added to a solution having 5.4 g of (2,3,4-trimethoxy-6- methylphenyl)(2,6-dichloro-4-trifluoromethyl-3- pyridyl)methanol obtained in step (a) dissolved in 14 0 mfi of toluene, followed by stirring under reflux by heating for 6 hours. The mixture was cooled and then subjected to filtration, and toluene was distilled off under reduced pressure to obtain 4.4 g (yield 81%) of 3-(2,3,4- trifluoromethylpyridine (compound No. 3; m.p. 81-83°C). SYNTHESIS EXAMPLE 2 Synthesis of 3-(2,3,4-trimethoxy-6-methylbenzoyl)-2- chloro-4-trifluoromethylpyridine (compound No. 11) and 3- (2,3,4-trimethoxy-6-methylbenzoyl)-4- trifluoromethylpyridine (compound No. 7) 2.4 mØ (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)-2,6- dichloro-4-trifluoromethylpyridine (compound No. 3) obtained in Synthesis Example 1 dissolved in 50 mfi of methanol, followed by stirring under hydrogen atmosphere for 6.5 hours. The mixture was subjected to filtration, 50 mfi 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-6- methylbenzoyl)-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)-4- trifluoromethylpyridine (compound No. 7; m.p. 59-62°C). SYNTHESIS EXAMPLE 3 Synthesis of 4-(2,3,4-trimethoxy-6-methylbenzoyl)-2,5- dichloro-3-trifluoromethylpyridine (compound No. 90) (a) 17 mfl (25 mmol) of n-butyllithium (1.5 M hexane solution) was dropwise added at 0°C to a solution having 3 . 6 mfl (25 mmol) of diisopropylamine dissolved in 60 mfl 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 mfl 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 mfl of toluene was added thereto, followed by stirring for 1 hours. 30 mfl 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-6- methylphenyl)(2,3,6-trichloro-5-trifluoromethyl-4- pyridy1)methanol (m.p. 131-135°C) . (b) 2.7 mfl (19 mmol) of triethylamine and 0.9 g of 5% palladium carbon were added to a solution having (2,3,4- trimethoxy-6-methylphenyl)(2,3,6-trichloro-5- trifluoromethyl-4-pyridyl)methanol obtained in step (a) dissolved in 200 mfl of methanol, followed by stirring under hydrogen atmosphere for 14 hours. The mixture was subjected to filtration, 30 ml of water was added thereto, and methanol 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 2.3 8 g (yield 24%) of (2,3,4- trimethoxy-6-methylphenyl)(2,5-dichloro-3- trifluoromethyl-4-pyridyl)methanol (m.p. 162-165°C). (c) 14 g of manganese dioxide was added to a solution having 3.5 g (8.2 mmol) of (2,3,4-trimethoxy-6- methylphenyl)(2,5-dichloro-3-trifluoromethyl-4- pyridyl)methanol obtained in step (b) dissolved in 100 ml of toluene, followed by stirring under reflux by heating for 6 hours. The mixture was cooled 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 3.1 g (yield 89%) of 4-(2,3,4-trimethoxy-6-methylbenzoyl- 2, 5-dichloro-3-trifluoromethylpyridine (compound No. 90; m.p. 106-109°C). SYNTHESIS EXAMPLE 4 Synthesis of 3-(4,5-dimethoxy-2-methylbenzoyl)-2-methoxy- 4-trifluoromethylpyridine (compound No. 32) 0.9 g (16 mmol) of sodium methoxide was added to a solution having 1.5 g (4.2 mmol) of 3-(4,5-dimethoxy-2- methylbenzoyl)-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 2 0 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)-2- methoxy-4-trifluoromethylpyridine (compound No. 32; m.p. 125-127°C). SYNTHESIS EXAMPLE 5 Synthesis of 3-[4,5-(methylenedioxy)-2-methylbenzoyl]-2- chloro-4-trifluoromethylpyridine (compound No. 13) (a) 3 .2 mfl (62 mmol) of bromine was dropwise added at 0°C to a solution having 7.0 mfl (58 mmol) of 3,4- (methylenedioxy)toluene and 5.5 mfl (68 mmol) of pyridine dissolved in 110 mfl of dichloromethane, followed by stirring for 3 0 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 obtained was purified by silica gel column chromatography to obtain 13 g (yield 99%) of 2-bromo-4,5- (methylenedioxy)toluene. (b) 13 ml (20 mmol) of n-butyllithium (1.5 M hexane 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 ml of tetrahydrofuran, followed by stirring for 30 minutes, and 1.5 ml (19 mmol) of dimethylformamide was added thereto, followed by stirring for 70 minutes. 30 ml of water was added to the mixture to terminate the reaction, and tetrahydrofuran was distilled off under reduced pressure. Extraction with chloroform was carried out, the organic layer was dried over anhydrous sodium sulfate and subjected to filtration by using a silica gel cake, and 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-methyl- 4,5-(methylenedioxy)benzaldehyde, 2.1 g (yield 73%) of (2-methyl-4,5-(methylenedioxy)phenyl)(2-chloro-4- trifluoromethyl-3-pyridyl)methanol (m.p. 127-130°C) was obtained by a process in accordance with step (a) of Synthesis Example 1. (d) Using 1.5 g (4.3 mmol) of (2-methyl-4,5- (methylenedioxy)phenyl)(2-chloro-4-trifluoromethyl-3- pyridyl)methanol obtained in step (c) and 8.0 g (92 mmol) of manganese dioxide, 0.3 g (yield 22%) of 3-[4,5- (methylenedioxy)-2-methylbenzoyl]-2-chloro-4- trifluoromethylpyridine (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)-2- chloro-4-trifluoromethylpyridine (compound No. 27) (a) A dimethylformamide (15 mfi) solution of 2- methoxy-4-methylphenol (6.91 g) was dropwise added to a dimethylformamide (20 ml) suspension of sodium hydride (2.4 g) under cooling with ice, followed by stirring for 3 0 minutes. A dimethylformamide (15 ml) 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 3 0 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- 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. (b) 4-benzyloxy-3-methoxytoluene (8.0 g) was dissolved in dimethylformamide (30 mfl) , and a dimethylformamide (15 mfl) solution of N-bromosuccinimide (6.36 g) was dropwise added thereto, followed by stirring at room temperature for one night. The reaction solution was poured into ice water (400 mfl) , and crystals thus deposited were collected by filtration, adequately washed with water, and dried for one night to obtain 10.64 g of 4-benzyloxy-2-bromo-5-methoxytoluene (m.p. 110-lll°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 (10 ml) 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 (200 mfl), and extraction with ethyl acetate (150 mfl) was 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 (hexane- ethyl acetate) to obtain 3.14 g (yield 48%) of 5- benzyloxy-4-methoxy-2-methylbenzaldehyde (m.p. 107- 109°C), and its structure was confirmed by nuclear magnetic resonance spectrum. (d) A hexane solution (11.4 mfi)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 tetrahydrofuran (7.5 mfi) solution of 2- chloro-4-trifluoromethylpyridine (2.81 g) was gradually added thereto, followed by stirring at the same temperature for 3 0 minutes. The solution was cooled to -78°C, and a tetrahydrofuran (37.5 mfi) solution of 5- 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 ml) was added thereto, the temperature was raised to room temperature, the mixture was poured into a saturated aqueous sodium bicarbonate solution (50 mfi), and extraction with ethyl acetate (150 mfl) was carried out twice. The ethyl acetate phase was washed with an aqueous sodium chloride solution (10 0 ml) and dried over magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane- ethyl acetate) to obtain 6.48 g (yield 96%) of (5- benzyloxy-4-methoxy-2-methylphenyl)(2-chloro-4- trifluoromethyl-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- 4-trifluoromethyl-3-pyridyl)methanol (5.9 g) was dissolved in a mixed solvent of anhydrous methylene chloride (50 ml) and acetonitrile (5 ml), and tetrapropylammonium perruthenate (95 mg), N- methylmorpholine-N-oxide (2.38 g) and molecular sieve 4A (6.8 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 ml) . The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (hexane- ethyl acetate) to obtain 4.93 g (yield 84%) of 3-(5- benzyloxy-4-methoxy-2-rnethylbenzoyl) -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)-2- methylthio-4-trifluoromethylpyridine (compound No. 50) Sodium methanethiolate (0.32 g) was added to a dimethylformamide (15 mfl) solution of 0.9 g of 3-(2,3,4- trimethoxy-6-methylbenzoyl)-2-chloro-4- trifluoromethylpyridine (compound No. 11) at room temperature, followed by stirring for 1 hour. The mixture was poured into water (50 ml) , and 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 (hexane- ethyl acetate) to obtain 0.54 g (yield 58%) of 3-(2,3,4- trimethoxy-6-methylbenzoyl)-2-methylthio-4- trifluoromethylpyridine (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)-3- acetyl-2,6-dichloro-4-trifluoromethylpyridine (compound No. 62) (a) 9.6 mfl (14 mmol) of n-butyllithium (1.5 M hexane solution) was dropwise added to a tetrahydrofuran (16 mfl) solution of 2.0 mfl (14 mmol) of diisopropylamine at 0°C, followed by stirring for 30 minutes. The solution was cooled to -50°C, a tetrahydrofuran (11 mfi) solution of 2.9 g (7 mmol) of (2,3,4-trimethoxy-6-methylphenyl)(2,6- dichloro-4-trifluoromethyl-3-pyridyl)methanol was added thereto, followed by stirring for 3 0 minutes, then the solution was cooled to -78°C, and acetaldehyde in an excess amount was added thereto, followed by stirring for 2 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 2.5 g (yield 78%) of (2,3,4-trimethoxy-6-methylphenyl)(2,6-dichloro-5-(1- hydroxyethyl)-4-trifluoromethyl-3-pyridyl)methanol. (b) 10 g of manganese dioxide was added to a toluene (80 mfi) solution of 2.3 g (5 mmol) of (2,3,4-trimethoxy- 6-methylphenyl)(2,6-dichloro-5-(1-hydroxyethyl)-4- trifluoromethyl-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-trimethoxy-6- methylbenzoyl)-3-acetyl-2,6-dichloro-4- trifluoromethylpyridine (compound No. 62; m.p. 109- 112°C). SYNTHESIS EXAMPLE 9 Synthesis of 4-(2,3,4-trimethoxy-6-methylbenzoyl)-2- chloro-3-trifluoromethyl-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 mfi (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-5- trifluoromethylpyridine was added thereto, followed by stirring for 3 0 minutes, and then a toluene 4 0 mfi solution of 21.0 g (100 mmol) of 2,3,4-trimethoxy-6- methylbenzaldehyde was added thereto, followed by stirring for 2 hours. 3 0 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-6- methylphenyl)(2,3-dichloro-5-trifluoromethyl-4- pyridyl)methanol (m.p. 95-98°C). (b) 2.1 g of 5% palladium carbon was added to a methanol 200 ml solution of 24.8 g (58.1 mmol) of (2,3,4- trimethoxy-6-methylphenyl)(2,3-dichloro-5- trifluoromethyl-4-pyridyl)methanol obtained in step (a) and 9.5 0 ml (68.2 mmol) of triethylamine, followed by stirring under hydrogen atmosphere for 4 hours. The mixture was subjected to filtration, 50 ml of water was added thereto, and methanol was distilled off under reduced pressure. The aqueous layer was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate 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 15.9 g (yield 7 0%) of (2,3,4-trimethoxy-6-methylphenyl)(3-chloro-5- trifluoromethyl-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 (2,3,4- trimethoxy-6-methylphenyl)(3-chloro-5-trifluoromethyl-4- 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-methylbenzoyl)-3- chloro-5-trifluoromethylpyridine (compound No. 102; m.p. 75-77°C). (d) 16.4 g (304 mmol) of sodium methoxide was added to a toluene 150 ml solution of 18.5 g (47.5 mmol) of 4- (2,3,4~trimethoxy-6-methylbenzoyl}-3-chloro-5- trifluoromethylpyridine obtained in step (c) and 16.6 ml (95.4 mmol) of hexamethylphosphoric triamide, followed by stirring under reflux 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-6- raethylbenzoyl)-3-methoxy~5~trifluoromethylpyridine (compound No. 122; m.p. 103-106°C). (e) 6.1 g (28 mmol) of m-chloroperbenzoic acid (m- CPBA) was added to a chloroform 100 mfl solution of 5.6 g (15 mmol) of 4-(2,3,4-trimethoxy-6-methylbenzoyl)-3- methoxy-5-trifluoromethylpyridine (compound No. 122} at 0°C, followed by stirring at room temperature for 18 hours. The reaction solution was washed with 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~5~ trifluoromethylpyridine-N-oxide (m.p. 128-134°C). (f) 1.8 mfl (19 mmol) of phosphorus oxychloride was added to 4 mfi of toluene and 8 mfi of dimethylformamide at 0°C, followed by stirring for 10 minutes, and 4.0 g (10 mmol) of 4-(2,3,4-trimethoxy-6-methylbenzoyl)-3-methoxy- 5-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-3- trifluoromethyl-5-methoxypyridine (compound No. 123; m.p. 117-119°C). SYNTHESIS EXAMPLE 10 Synthesis of 4-(2,3,4-trimethoxy-6-methylbenzoyl)-2- bromo-3-trifluoromethyl-5-methoxypyridine (compound No. 124) Using 7.2 g (18 mmol) of 4-(2,3,4-trimethoxy-6- methylbenzoyl)-3-methoxy-5-trifluoromethylpyridine-N- oxide, 7 ml of toluene, 17 ml of dimethylformamide and 10 g (35 mmol) of phosphorus oxybromide, 4.1 g (yield 49%) of 4-(2,3,4-trimethoxy-6-methylbenzoyl)-2-bromo-3- trifluoromethyl-5-methoxypyridine (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)-2,3,5- trichloropyridine (compound No. 186) (a) 17.2 ml (26.7 mmol) of n-butyllithium (1.56 M hexane solution) was dropwise added to a diethyl ether (20 mfi) 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. 3 0 mfi 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 (2,3,4- trimethoxy-6-methylphenyl)(2,3,5-trichloro-4- pyridyl)methanol. (b) 16.2 g of manganese dioxide was added to a toluene (180 mfi) solution of 5.6 g of (2,3,4-trimethoxy- 6-methylphenyl)(2,3,5-trichloro-4-pyridyl)methanol obtained in step (a), followed by stirring under reflux 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 4.7 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 12 Synthesis of 4-(2,3,4-trimethoxy-6-methylbenzoyl)-3,5- dichloropyridine (compound No. 191) 4.6 g (6.9 mmoDof triethylamine and 1.8 g of 10% palladium carbon were added to a methanol 2 80 mfi solution of 17.8 g (4.6 mmol) of 4-(2,3,4-trimethoxy-6- methylbenzoyl)-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-6- methylbenzoyl)-3,5-dichloropyridine (compound No. 191; m.p. 109-lll°C). SYNTHESIS EXAMPLE 13 Synthesis of 4-(2,3,4-trimethoxy-6-methylbenzoyl)-3- chloro-5-methoxypyridine (compound No. 244) 5.0 g (2.8 mmol) of hexamethylphosphoric triamide and 1.1 g (2.1 mmol) of sodium methoxide were added to a toluene (60 mfi) solution of 5.0 g (1.4 mmol) of 4-(2,3,4- trimethoxy-6-methylbenzoyl)-3,5-dichloropyridine (compound No. 191), followed by stirring under reflux by heating for 5 hours. After the mixture was cooled, 50 ml 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 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 4- (2,3,4-trimethoxy-6-methylbenzoyl)-3-chloro-5- methoxypyridine (compound No. 244; pale yellow oily substance). SYNTHESIS EXAMPLE 14 Synthesis of 4-(2,3,4-trimethoxy-6-methylbenzoyl)-2,3- dichloro-5-methoxypyridine (compound No. 193) (a) A chloroform (60 mfi) solution of 3.4 g (1 mmol) of 4-(2,3,4-trimethoxy-6-methylbenzoyl)-3-chloro-5- methoxypyridine (compound No. 244) was cooled with ice, 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. 3 0 mfi of a 0.5 mol/l 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-6- methylbenzoyl)-3-chloro-5-methoxypyridine-N-oxide (m.p. 160-166°C). (b) 5 mfi of dimethylformamide was added to 2.5 mfi of toluene, the mixture was cooled with ice, and 1.3 mG (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-(2,3,4- trimethoxy-6-methylbenzoyl)-3-chloro-5-methoxypyridine-N- oxide was added thereto. After the mixture was stirred under cooling with ice for 3 0 minutes, the temperature 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 thereto for extraction. The organic layer was dried over anhydrous sodium sulfate, subjected to filtration and purified by silica gel column chromatography to obtain 2.0 g (yield 76%) of 4-(2,3,4-trimethoxy-6- methylbenzoyl)-2,3-dichloro-5-methoxypyridine (compound No. 193; m.p. 98-99°C) . SYNTHESIS EXAMPLE 15 Synthesis of 4-(2,3,4-trimethoxy-6-methylbenzoyl)-2bromo- 3-chloro-5-methoxypyridine (compound No. 245) 5 mfi of dimethylformamide was added to 2.5 mfi 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-(2,3,4- trimethoxy-6-methylbenzoyl)-3-chloro-5-methoxypyridine-N- oxide obtained in Synthesis Example 14 (a) was added thereto. After the mixture was stirred under cooling with ice for 3 0 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-3- chloro-5-methoxypyridine (compound No. 245; m.p. 97- 99°C). SYNTHESIS EXAMPLE 16 Synthesis of 4-(2,3,4-trimethoxy-6-methylbenzoyl)-3- bromo-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 mfi 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-trimethoxy-6- methylphenyl)(3,5-dibromo-4-pyridyl)methanol (yellow oily substance). (b) A tetrahydrofuran (15 mfi) solution of 2.0 g (4.6 mmol) of (2,3,4-trimethoxy-6-methylphenyl)(3,5-dibromo-4- pyridyl)methanol obtained in step (a) was cooled to -78°C, 6.0 mfi (9.4 mmol) of n-butyllithium (1.56 M hexane solution) was dropwise added thereto, followed by stirring for 5 minutes, and 0.5 mfi (8.0 mmol) of methyl iodide was added thereto, followed by stirring for 2.5 hours. 20 mfi 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-6- methylphenyl)(3-bromo-5-methyl-4-pyridyl)methanol. (c) 3 g of manganese dioxide was added to a toluene (30 mfi) solution of 0.43 g (1.1 mmol) of (2,3,4- trimethoxy-6-methylphenyl)(3-bromo-5-methyl-4- 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-(2,3,4- trimethoxy-6-methylbenzoyl)-3-bromo-5-methylpyridine (compound No. 228; m.p. 88-93°C). SYNTHESIS EXAMPLE FOR AN INTERMEDIATE Now, Synthesis Example of 2,3,4-trimethoxy-6- methylbenzaldehyde 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 ml) solution of 128 g (0.7 mol) of 3,4,5-trimethoxytoluene was dropwise added to a dry methylene chloride 500 mfl 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 16 of ice water, the methylene chloride phase was separated, and the aqueous phase was extracted with 2 00 mfl of methylene chloride twice. The extract and the methylene chloride phase were combined together, sequentially washed with 200 ml of water, 200 mfl of a saturated aqueous sodium bicarbonate solution and 200 mfl 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 resulting crystal was collected by filtration, washed with hexane and air dried to obtain 128 g of 2,3,4- trimethoxy-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 (1-1) 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. Compounds represented by the formula (X) to 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 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. The benzoylpyridine derivative represented by the formula (I) or its salt is useful as an active ingredient for a fungicide, particularly as an active ingredient for an agricultural and horticultural fungicide. As the agricultural and horticultural fungicide, it is effective for 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 pumila); scab or black spot of pear (Pyrus serotina, Pyrus ussuriensis, Pyrus 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 melo); 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 chiloensis); 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 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 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 alkyl aryl phosphoric ester salt or a salt of a 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 ether, an acetylene glycol, an acetylene alcohol, an 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 oil, 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 0.2:99.8 to 90:10. These formulations can be practically used either as they are or after they are diluted with a diluent such as water to predetermined concentrations and a spreading agent is added thereto as the case requires. The concentration of the compound of the present invention varies depending upon the crop plant as the 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, atomizing, 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% of 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) of 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, Propoxur, Aldicarb, Carbofuran, Thiodicarb, Methomyl, Oxamyl, Ethiofencarb, Pirimicarb, Fenobucarb, Carbosulfan and Benfuracarb; nelicetoxin derivatives such as Cartap and Thiocyclam; 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, Triazamate, Pymetrozine, Pyrimidifen, Chlorfenapyr, Indoxacarb, Acequinocyl, Etoxazole, Cyromazine and 1,3- dichloropropene; 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, Myclobutanil, Cyproconazole, Terbuconazole, Hexaconazole, Furconazole-cis, Prochloraz, Metconazole, Epoxiconazole, Tetraconazole, Oxpoconazole fumarate and Sipconazole; quinoxaline type compounds such as Quinomethionate; dithiocarbamate type compounds such as Maneb, Zineb, 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 Cyazofamid; 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, O- diisopropylphosphorothioate, O-ethyl S,S- diphenylphosphorodithioate 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; urea type compounds such as Pencycuron; cinnamic acid type compounds such as Dimethomorph; phenyl carbamate type compounds such as Diethofencarb; cyanopyrrole type compounds such as Fludioxonil and Fenpiclonil; strobilurin type compounds such as Azoxystrobin, Kresoxim-Methyl, Metominofen, Triflouxystrobin, Picoxystrobin and Pyraclostrobin: (BAS 500F); oxazolidinone type compounds such as Famoxadone; thiazole carboxamide type compounds such as Ethaboxam; silyl amide type compounds such as Silthiopham; aminoacid amidecarbamate 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 BJL-993, BJL-994, BAS-510, BAS-505, MTF-753 andUIBF-307. Now, Test Examples of the agricultural and 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] 5 : No lesions nor sporogony recognizable 4 : Area of lesions, number of lesions or area of sporogony is less than 10% of non-treated plot 3 : Area of lesions, number of lesions or area of sporogony is less than 40% of non-treated plot 2 : Area of lesions, number of lesions or area of sporogony is less than 70% of non-treated plot 1 : Area of lesions, number of lesions or area of sporogony is at least 70% of non-treated plot TEST EXAMPLE 1 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 2 0°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, 114, 117, 119, 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, 35, 36, 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, 123, 124, 133, 136, 142, 186, 187, 188, 189, 190, 191, 192, 193, 194, 199, 200, 210, 211, 213, 228, 243, 245, 249, 252, 254, 272, 287, 288, 289, 290, 291 and 292 showed effects with a controlling index of 4 or above at a concentration of 12 5 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, and 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 for 24 hours, and then kept in a thermostatic chamber at 2 0°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 12 5 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 ml 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 the compounds Nos. 9, 11, 55, 90 and 102 showed effects with a controlling index of 4 or above at a concentration of 12 5 ppm. TEST EXAMPLE 4 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 ml 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 cucumber was sprayed and inoculated with a conidiospore suspension of fungi of powdery mildew, and the cucumber was kept in a thermostatic chamber at 2 0 °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 4 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 12 5 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. FORMULATION EXAMPLE 1 (1) Compound of the present invention 20 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 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 2 0 parts by weight (2) N,N'-dimethylacetamide 2 0 parts by weight (3) Polyoxyethylene alkyl phenyl ether 10 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 5 parts by weight (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 50 parts by weight (2) Oxylated polyalkylphenyl phosphate- triethanolamine 2 parts by weight (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. FORMULATION EXAMPLE 6 (1) Compound of the present invention 5 parts by weight (2) Polyoxyethylene octylphenyl ether 1 part by weight (3) Phosphate of polyoxyethylene 0.1 part by weight (4) Particulate calcium carbonate 93.9 parts by weight 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 9 5.0 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 2 0 parts by weight (2) Oxylated polyalkylphenol phosphate 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 represented by the formula (I) or its salt has excellent effects as an active ingredient of a fungicide. 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 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.

Full Text

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.
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
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)
or its salt:
wherein
X is a fluorine atom, a chlorine atom, a bromine atom, a iodine atom,
a nitro group,
an Ci-o alkoxy group which may be substituted by
a C6-10 aryl,
a C6-10 aryloxy,
a hydroxyl,
a nitro,
a nitroxy,
a halogen,
a C1-4 haloalkoxy,
a C5-6 cycloalkyl,
amino,
a C1-6 alkylthio or
a cyano;
a naphthyloxy group which may be substituted by
a halogen,
a C1-6 alkyl or
a hydroxyL'
a phenoxy group which may be substituted by
a halogen,
a C1-6 alkyl or
a hydroxyl;
a C6-10 cycloalkoxy group which may be substituted by
a halogen ox
a hydroxyL"
a hydroxyl group;
a hydrocarbon group selected from
a C1-6 alkyl,
a C2-6 aBcenyl group,
a C2-6 alkynyl group,
a C5-6 cydoalkyl group, and
a C5-10 aryl group,
which groups may be substituted by
a C5-10 aryl,
a C5-10 aryloxy,
a hydroxyl,
anitro,
anitroxy,
a halogen,
a C1-4 haloalkoxy,
a Ca-a cycloaliyl,
a C1-0 alkylthio or
acyano;
a C1-0 alkylthio group which may be substituted by
a C6-10 aryl,
a C6-10 aryloxy,
a hydroxyl,
anitro,
anitroxy,
a halogen,
a C1-4 haloalkoxy or
acyano;
a eyano group;
a C1-6 alkoxycarbonyl group;
a nitroxy C1-4 alkoxyaminocarbonyl group!
a phenyl C1-4 alkoxycarbonyl group;
a carbamoyl group!
a mono C1-6 alkylaminocarbonyl group;
a di C1-6 alkylaminocarbonyl group;
a nitroxy C1-4 alkylaminocarbonyl group;
a phenyl C1-4 alkylaminocarbonyl group;
a Ca-6 cycloalkylamicnocarbonyl group;
a moxpbolinocarbonyl group!
a piperidinocarbonyl group;
a pyrrolidmocarbojiyl group;
a tbiomorpnolinocarbonyl group;
an aminocarbonyl group;
an amino group, a mono C1-4 alkylamino group or
a di C1-4 alkylamino group;
n is 1, 2, 3 or 4'
R1 is a C1-6 alkyl group;
R2'is a C1-6 alkyl group,
a C1-6 alkoxy group,
p ia 1, 2 or 3, and
R2" is a C1-4 alkoxy group
with the proviso that (l) the pyridine ring is not substituted by the benzoyl
group at the 2-position; the pyridine ring is substituted, by a C1-6 alkoxy group,
a hydroxyl group or a benzyloxy group at the 3-position>' and n is 1, p is 1 and
that (2) the pyridine ring is not substituted by a chlorine atom or bromine atom
at the 2-position and n is 1.
Preferably the benzoylpyridine derivative or its salt is represented by the formula (I")
wherein X is a halogen atom,
a nitro group,
a C1-6 alkoxy group which may be substituted by
a C1-6 aryl,
a C1-6 aryloxy,
a hydroxyl,
anitro,
a nitroxy,
a halogen,
a C1-4 haloalkoxy,
a C1-6 cydoalkyl,
an amino,
a C1-6 alkylthio or
a cyanol
a naphthyloxy group which may be substituted by
a Halogen,
a hydroxyl;
a phenoxy group which, may be substituted by
a halogen,.
a C1-6 alkyl or
a hydxoxyL
a C1-6 cycloalkoxy group which may be substituted by
a halogen or
a hydroxyl;
a hydrocarbon, group selected from
a C1-6 alkyl,
a C2-6 alkenyl group,
a C2-6 alkynyl group,
a Ca-6 cydoalkyl group, and
a C5-10 aryl group,
which groups may be substituted by
a C6-10 aryl,
a C6-10 aryloxy,
a hydroxyl,
a nitro,
a nitroxy,
a halogen,
a C1-4 haloalkoxy,
a C5-6 cycloaliyl,
an amiiio,
a C1-6 alkylthio or
a cyano!
a C1-6 alkylthio group which may be substituted by
a C5-10 aryl,
a C5-10 aryloxy,
a hydroxyl,
a nitro,
a nitroxy,
a halogen,
a C1-6 haloalkoxy or
a cyano;
a cyano group,
a C1-6 alkoxycarbonyl group,
a nitroxy C1-4 alkoxyaminocarbonyl group,
a phenyl C1-4 alkoxycarbonyl group,
a carbamoyl group,
a mono C1-6 alkylaminocafbonyl group,
a di C1-6 alkylaminocarborLyl group,
a nitroxy C1-4 alkylaminocarbonyl group,
a phenyl C1-4 alkylaminocarbonyl group,
a C3-6 cycloalkylaminocarbonyl group,
a morphoi i nncarbonyl group;
a piperidinocarbonyl group;
a pyrrolidinocarbonyl group;
a thioinorpholinocarbonyl group;
an aminocarbonyl group,
an amino group,
a mono C1-4 alkylamino group or
a di C1-4 alkylamino group;
n is 1, 2, 3 or 4;
R1 is a C1-6 alkyl group!
R2' is a C1-6 alkyl group or
a C1-6 alkoxy group;
p is 1, 2 or 3, and each of
R2" and R2"1 is a C1-6 alkoxy group.
More preferably the benzoylpyridine derivative or its salt is represented by the formula (I'')
wherein X is a halogen atom,
a C1-6 alkoxy group,
a C1-6 alkyl group,
a CF3 group or
a Ci-c alkylthio group;
n ia 1, 2, 3 or 4;
R1s a Ci-g alkyl group;
R2'is a C1-6 alkyl group or
a C1-6 alkoxy group;
p is 1, 2 or 3; and
each of R2" and R2" is a C1-6 alkoxy group.
More preferably the benzoylpyridine derivative or its salt is represented by the formula (I"")
wnexein
X is a. halogen atom,
a C1-6 alkoxy group,
a C1-6 alkyl group,
a CFs group or
a C1-4 aliylthio group;
n is 1, 2 or 3;
R1 is a C1-6 alkyl group;
R2'is a C1-6 alkoxy group;
p is 1, 2 or 8, and
each of R2" and R2'' is a C1-6 alkoxy group.
wherein
B is -CX4= whenAis -N=;
B is -N= whenAis -CH=;
each, of X1 and X2 which are independent of each other, is
a halogen atom,
a C1-6 alkoxy group,
a C1-6 alkyl group,
a CPs group or
a C1-6 alkylthio group!
X3 is a hydrogen atom,
a halogen atom,
a C1-6 alkoxy group,
a C1-6 alkyl group,
a CFs group or
a C1-6 alkylthio group ?
X4 is a hydrogen atom,
a halogen atom,
a C1-6 alkoxy group,
a C1-6 alkyl group,
a CF3 group or
a C1-6 alkylthio group,
IVis a C1-6 alkyl group!
R2" is a C1-6 alkoxy group;
p is 1, 2 or 3; and
each of R2" and R2" is a C1-6 alkoxy group .
The benzoylpyridine derivative represented by the formula (I') or its salt for preventing
I curing fungal diseases.
The present invention also provides a process for producing a benzoylpyridine derivative
represented by the formula (I') or its salt:
wherein X, n and R1 are as defined in claim 1,
R2' is a C1-6 aliyl group or a C1-6 alkoxy group,
p is 1, 2 or 3, and
R2" is a C1-6 alkoxy group
with the proviso that (1) the pyridine ring is not substituted by the benzoyl
group at the 2-position; the pyridine ring is substituted by a C1-6 alkoxy
group, a hydroxyl group or a benzyloxy group at the 3-positionJ and n is 1, p is 1
and (2) that the pyridine ring is not substituted by a chlorine atom or bromine
atom at the 2-position and n ia 1,
which process comprises reacting a substituted benzaldehyde represented by
the formula (VI-1'):
(wherein R1, R2', R2" and p are as defined above) and a metal salt of a
substituted pyridine derivative represented by the formula (VIM) -
(wherein X is as defined above, and Z is a metal atom such as lithium,
magnesium, zinc or copper, or a transition metal atom such as palladium
or ruthemium or a composite salt thereof) to produce phenylpyridyl methanol
represented by the formula (X1):
(wherein X, n, p, R1, R2' and R2" are as defined above, with a proviso as in
formula (I')), and oxidizing it.
A preferred embodiment is a process for producing a benzoylpyridine derivative represented
by the formula (I1) or its salt:
wherein X, n and Rl are
R2 is a C1-6 alkyl group or
a C1-6 ajkoxy group,
p is 1, 2 or 3, and R2 is a C1-6 alkoxy group
with the proviso that (l) the pyridine ring is not substituted by the benzoyl
group at the 2-position>' the pyridine ring is substituted by a C1-6 alkoxy
.group, a hydroxyl group or a benzyloxy group at the 3-position; and n is 1, p is 1
and (2) that the pyridine ring is not substituted by a chlorine atom or bromine
atom at the 2-position and n is 1,
which process comprises reacting a metal salt of a substituted benzene
derivative represented by the formula (VI-21)'
(wherein Rl, R2", R2" and p are as defined above and
Z is a metal atom such as lithium, magnesium, zinc or copper, or a transition
metal atom such as palladium or ruthemium 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 (X1):
(wherein X, n, p, R1 ,R2'and R2" are as defined above with a proviso as in
formula (I')), and oxidizing it,
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, R2, n
and m in the formulae are as defined above. One of the
substituents represented by M1 in the formula (II) and M2
in the formula (III) is a cyano group, and the other is a
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
18
by the formula (III) to a condensation reaction to
produce an imine compound represented by the formula
(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
it.
The metal atom represented by each of M1 and M2 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
M2 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
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
solvent thereof) at a reaction temperature of from -10 0
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
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, R2, 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 benzenesulfinate or sodium p-toluenesulfinate may
be 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 triethylammonium 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
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
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
oxidizing agent such as manganese dioxide or chromic
acid, a Swern oxidation method (dimethylsulfoxide +
oxalyl chloride) or a ruthenium oxidation method
(tetrapropylammonium perruthenate + N-methylmorpholine-N-
oxide) and converted to a compound represented by the
formula (I)
Now, mode of carrying out Process 3 is described
below.
(1) A process for producing the compound represented
by the formula (I), which comprises reacting a
substituted benzaldehyde represented by the formula (VI-
1) :
(wherein R1, R2 and m 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), 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):
(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):
(wherein X is as defined above), to produce phenylpyridyl
5 methanol represented by the formula (X), and oxidizing
it.
Here, the preferred modes of the phenylpyridyl
methanol represented by the formula (X) which is an
intermediate for production of the compound represented
by the formula (I) are shown below.
(1) Phenylpyridyl methanol represented by the
formula (X'):
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 R2" 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 phenylpyridyl methanol according to the
above item (1), which is represented by the formula
(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
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
0 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 phenylpyridyl methanol according to the
above item (5), which is represented by the formula
5 (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.
(7) The phenylpyridyl methanol according to the
above item (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
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 (I). Here, in the formula (I-
a), E is an electrophilic reagent, and in the formula (I-
b), Nu is a nucleophilic reagent.
n' and n' are as defined for the above n.

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
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 (I-
c) (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.
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 of 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-
c) . Further, the reaction may be carried out in the
presence of a base such as triethylamine or sodium
hydrogen carbonate. Further, a known reduction reaction
may be employed such as hydrogen transfer reaction (e.g.
palladium carbon, ammonium formate as a hydrogen source,
or sodium dihydrogen phosphate) or a metal reduction
reaction (e.g. samarium diiodide).
Now, specific Synthesis Examples of the
benzoylpyridine derivative represented by the formula (I)
and the intermediate for its production are described
below (the compounds in Synthesis Examples are based on
IUPAC nomenclature, and the substitution positions may be
different from those shown in Tables as mentioned
hereinafter, expediently).
SYNTHESIS EXAMPLE 1
Synthesis of 3-(2,3,4-trimethoxy-6-methylbenzoyl)-2,6-
dichloro-4-trifluoromethylpyridine (compound No. 3)
(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 mfi (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 mfi of tetrahydrofuran was added thereto,
followed by stirring for 1.5 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 6.2 g (yield 81%) of (2,3,4-trimethoxy-6-
methylphenyl)(2,6-dichloro-4-trifluoromethyl-3-
pyridyl)methanol (brown oily substance).
(b) 14 g of manganese dioxide was added to a
solution having 5.4 g of (2,3,4-trimethoxy-6-
methylphenyl)(2,6-dichloro-4-trifluoromethyl-3-
pyridyl)methanol obtained in step (a) dissolved in 14 0 mfi
of toluene, followed by stirring under reflux by heating
for 6 hours. The mixture was cooled and then subjected
to filtration, and toluene was distilled off under
reduced pressure to obtain 4.4 g (yield 81%) of 3-(2,3,4-
trifluoromethylpyridine (compound No. 3; m.p. 81-83°C).
SYNTHESIS EXAMPLE 2
Synthesis of 3-(2,3,4-trimethoxy-6-methylbenzoyl)-2-
chloro-4-trifluoromethylpyridine (compound No. 11) and 3-
(2,3,4-trimethoxy-6-methylbenzoyl)-4-
trifluoromethylpyridine (compound No. 7)
2.4 mØ (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)-2,6-
dichloro-4-trifluoromethylpyridine (compound No. 3)
obtained in Synthesis Example 1 dissolved in 50 mfi of
methanol, followed by stirring under hydrogen atmosphere
for 6.5 hours. The mixture was subjected to filtration,
50 mfi 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-6-
methylbenzoyl)-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)-4-
trifluoromethylpyridine (compound No. 7; m.p. 59-62°C).
SYNTHESIS EXAMPLE 3
Synthesis of 4-(2,3,4-trimethoxy-6-methylbenzoyl)-2,5-
dichloro-3-trifluoromethylpyridine (compound No. 90)
(a) 17 mfl (25 mmol) of n-butyllithium (1.5 M hexane
solution) was dropwise added at 0°C to a solution having
3 . 6 mfl (25 mmol) of diisopropylamine dissolved in 60 mfl
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 mfl 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 mfl of toluene was added thereto, followed
by stirring for 1 hours. 30 mfl 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-6-
methylphenyl)(2,3,6-trichloro-5-trifluoromethyl-4-
pyridy1)methanol (m.p. 131-135°C) .
(b) 2.7 mfl (19 mmol) of triethylamine and 0.9 g of 5%
palladium carbon were added to a solution having (2,3,4-
trimethoxy-6-methylphenyl)(2,3,6-trichloro-5-
trifluoromethyl-4-pyridyl)methanol obtained in step (a)
dissolved in 200 mfl of methanol, followed by stirring
under hydrogen atmosphere for 14 hours. The mixture was
subjected to filtration, 30 ml of water was added
thereto, and methanol 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 2.3 8 g (yield 24%) of (2,3,4-
trimethoxy-6-methylphenyl)(2,5-dichloro-3-
trifluoromethyl-4-pyridyl)methanol (m.p. 162-165°C).
(c) 14 g of manganese dioxide was added to a
solution having 3.5 g (8.2 mmol) of (2,3,4-trimethoxy-6-
methylphenyl)(2,5-dichloro-3-trifluoromethyl-4-
pyridyl)methanol obtained in step (b) dissolved in 100 ml
of toluene, followed by stirring under reflux by heating
for 6 hours. The mixture was cooled 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
3.1 g (yield 89%) of 4-(2,3,4-trimethoxy-6-methylbenzoyl-
2, 5-dichloro-3-trifluoromethylpyridine (compound No. 90;
m.p. 106-109°C).
SYNTHESIS EXAMPLE 4
Synthesis of 3-(4,5-dimethoxy-2-methylbenzoyl)-2-methoxy-
4-trifluoromethylpyridine (compound No. 32)
0.9 g (16 mmol) of sodium methoxide was added to a
solution having 1.5 g (4.2 mmol) of 3-(4,5-dimethoxy-2-
methylbenzoyl)-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 2 0 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)-2-
methoxy-4-trifluoromethylpyridine (compound No. 32; m.p.
125-127°C).
SYNTHESIS EXAMPLE 5
Synthesis of 3-[4,5-(methylenedioxy)-2-methylbenzoyl]-2-
chloro-4-trifluoromethylpyridine (compound No. 13)
(a) 3 .2 mfl (62 mmol) of bromine was dropwise added at
0°C to a solution having 7.0 mfl (58 mmol) of 3,4-
(methylenedioxy)toluene and 5.5 mfl (68 mmol) of pyridine
dissolved in 110 mfl of dichloromethane, followed by
stirring for 3 0 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
obtained was purified by silica gel column chromatography
to obtain 13 g (yield 99%) of 2-bromo-4,5-
(methylenedioxy)toluene.
(b) 13 ml (20 mmol) of n-butyllithium (1.5 M hexane
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 ml of
tetrahydrofuran, followed by stirring for 30 minutes, and
1.5 ml (19 mmol) of dimethylformamide was added thereto,
followed by stirring for 70 minutes. 30 ml of water was
added to the mixture to terminate the reaction, and
tetrahydrofuran was distilled off under reduced pressure.
Extraction with chloroform was carried out, the organic
layer was dried over anhydrous sodium sulfate and
subjected to filtration by using a silica gel cake, and
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-methyl-
4,5-(methylenedioxy)benzaldehyde, 2.1 g (yield 73%) of
(2-methyl-4,5-(methylenedioxy)phenyl)(2-chloro-4-
trifluoromethyl-3-pyridyl)methanol (m.p. 127-130°C) was
obtained by a process in accordance with step (a) of
Synthesis Example 1.
(d) Using 1.5 g (4.3 mmol) of (2-methyl-4,5-
(methylenedioxy)phenyl)(2-chloro-4-trifluoromethyl-3-
pyridyl)methanol obtained in step (c) and 8.0 g (92 mmol)
of manganese dioxide, 0.3 g (yield 22%) of 3-[4,5-
(methylenedioxy)-2-methylbenzoyl]-2-chloro-4-
trifluoromethylpyridine (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)-2-
chloro-4-trifluoromethylpyridine (compound No. 27)
(a) A dimethylformamide (15 mfi) solution of 2-
methoxy-4-methylphenol (6.91 g) was dropwise added to a
dimethylformamide (20 ml) suspension of sodium hydride
(2.4 g) under cooling with ice, followed by stirring for
3 0 minutes. A dimethylformamide (15 ml) 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 3 0 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-
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.
(b) 4-benzyloxy-3-methoxytoluene (8.0 g) was
dissolved in dimethylformamide (30 mfl) , and a
dimethylformamide (15 mfl) solution of N-bromosuccinimide
(6.36 g) was dropwise added thereto, followed by stirring
at room temperature for one night. The reaction solution
was poured into ice water (400 mfl) , and crystals thus
deposited were collected by filtration, adequately washed
with water, and dried for one night to obtain 10.64 g of
4-benzyloxy-2-bromo-5-methoxytoluene (m.p. 110-lll°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 (10 ml)
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 (200
mfl), and extraction with ethyl acetate (150 mfl) was
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 (hexane-
ethyl acetate) to obtain 3.14 g (yield 48%) of 5-
benzyloxy-4-methoxy-2-methylbenzaldehyde (m.p. 107-
109°C), and its structure was confirmed by nuclear
magnetic resonance spectrum.
(d) A hexane solution (11.4 mfi)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 tetrahydrofuran (7.5 mfi) solution of 2-
chloro-4-trifluoromethylpyridine (2.81 g) was gradually
added thereto, followed by stirring at the same
temperature for 3 0 minutes. The solution was cooled to
-78°C, and a tetrahydrofuran (37.5 mfi) solution of 5-
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 ml) was added thereto, the
temperature was raised to room temperature, the mixture
was poured into a saturated aqueous sodium bicarbonate
solution (50 mfi), and extraction with ethyl acetate (150
mfl) was carried out twice. The ethyl acetate phase was
washed with an aqueous sodium chloride solution (10 0 ml)
and dried over magnesium sulfate, and the solvent was
distilled off under reduced pressure. The residue was
purified by silica gel column chromatography (hexane-
ethyl acetate) to obtain 6.48 g (yield 96%) of (5-
benzyloxy-4-methoxy-2-methylphenyl)(2-chloro-4-
trifluoromethyl-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-
4-trifluoromethyl-3-pyridyl)methanol (5.9 g) was
dissolved in a mixed solvent of anhydrous methylene
chloride (50 ml) and acetonitrile (5 ml), and
tetrapropylammonium perruthenate (95 mg), N-
methylmorpholine-N-oxide (2.38 g) and molecular sieve 4A
(6.8 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 ml) . The solvent was
distilled off under reduced pressure, and the residue was
purified by silica gel column chromatography (hexane-
ethyl acetate) to obtain 4.93 g (yield 84%) of 3-(5-
benzyloxy-4-methoxy-2-rnethylbenzoyl) -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)-2-
methylthio-4-trifluoromethylpyridine (compound No. 50)
Sodium methanethiolate (0.32 g) was added to a
dimethylformamide (15 mfl) solution of 0.9 g of 3-(2,3,4-
trimethoxy-6-methylbenzoyl)-2-chloro-4-
trifluoromethylpyridine (compound No. 11) at room
temperature, followed by stirring for 1 hour. The
mixture was poured into water (50 ml) , and 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 (hexane-
ethyl acetate) to obtain 0.54 g (yield 58%) of 3-(2,3,4-
trimethoxy-6-methylbenzoyl)-2-methylthio-4-
trifluoromethylpyridine (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)-3-
acetyl-2,6-dichloro-4-trifluoromethylpyridine (compound
No. 62)
(a) 9.6 mfl (14 mmol) of n-butyllithium (1.5 M hexane
solution) was dropwise added to a tetrahydrofuran (16 mfl)
solution of 2.0 mfl (14 mmol) of diisopropylamine at 0°C,
followed by stirring for 30 minutes. The solution was
cooled to -50°C, a tetrahydrofuran (11 mfi) solution of
2.9 g (7 mmol) of (2,3,4-trimethoxy-6-methylphenyl)(2,6-
dichloro-4-trifluoromethyl-3-pyridyl)methanol was added
thereto, followed by stirring for 3 0 minutes, then the
solution was cooled to -78°C, and acetaldehyde in an
excess amount was added thereto, followed by stirring for
2 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 2.5 g (yield 78%) of
(2,3,4-trimethoxy-6-methylphenyl)(2,6-dichloro-5-(1-
hydroxyethyl)-4-trifluoromethyl-3-pyridyl)methanol.
(b) 10 g of manganese dioxide was added to a toluene
(80 mfi) solution of 2.3 g (5 mmol) of (2,3,4-trimethoxy-
6-methylphenyl)(2,6-dichloro-5-(1-hydroxyethyl)-4-
trifluoromethyl-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-trimethoxy-6-

methylbenzoyl)-3-acetyl-2,6-dichloro-4-
trifluoromethylpyridine (compound No. 62; m.p. 109-
112°C).
SYNTHESIS EXAMPLE 9
Synthesis of 4-(2,3,4-trimethoxy-6-methylbenzoyl)-2-
chloro-3-trifluoromethyl-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 mfi (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-5-
trifluoromethylpyridine was added thereto, followed by
stirring for 3 0 minutes, and then a toluene 4 0 mfi
solution of 21.0 g (100 mmol) of 2,3,4-trimethoxy-6-
methylbenzaldehyde was added thereto, followed by
stirring for 2 hours. 3 0 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-6-
methylphenyl)(2,3-dichloro-5-trifluoromethyl-4-
pyridyl)methanol (m.p. 95-98°C).
(b) 2.1 g of 5% palladium carbon was added to a
methanol 200 ml solution of 24.8 g (58.1 mmol) of (2,3,4-
trimethoxy-6-methylphenyl)(2,3-dichloro-5-
trifluoromethyl-4-pyridyl)methanol obtained in step (a)
and 9.5 0 ml (68.2 mmol) of triethylamine, followed by
stirring under hydrogen atmosphere for 4 hours. The
mixture was subjected to filtration, 50 ml of water was
added thereto, and methanol was distilled off under
reduced pressure. The aqueous layer was extracted with
ethyl acetate, and the organic layer was dried over
anhydrous sodium sulfate 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 15.9 g (yield 7 0%) of
(2,3,4-trimethoxy-6-methylphenyl)(3-chloro-5-
trifluoromethyl-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 (2,3,4-
trimethoxy-6-methylphenyl)(3-chloro-5-trifluoromethyl-4-
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-methylbenzoyl)-3-
chloro-5-trifluoromethylpyridine (compound No. 102; m.p.
75-77°C).
(d) 16.4 g (304 mmol) of sodium methoxide was added
to a toluene 150 ml solution of 18.5 g (47.5 mmol) of 4-
(2,3,4~trimethoxy-6-methylbenzoyl}-3-chloro-5-
trifluoromethylpyridine obtained in step (c) and 16.6 ml
(95.4 mmol) of hexamethylphosphoric triamide, followed by
stirring under reflux 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-6-
raethylbenzoyl)-3-methoxy~5~trifluoromethylpyridine
(compound No. 122; m.p. 103-106°C).
(e) 6.1 g (28 mmol) of m-chloroperbenzoic acid (m-
CPBA) was added to a chloroform 100 mfl solution of 5.6 g
(15 mmol) of 4-(2,3,4-trimethoxy-6-methylbenzoyl)-3-
methoxy-5-trifluoromethylpyridine (compound No. 122} at
0°C, followed by stirring at room temperature for 18
hours. The reaction solution was washed with 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~5~
trifluoromethylpyridine-N-oxide (m.p. 128-134°C).
(f) 1.8 mfl (19 mmol) of phosphorus oxychloride was
added to 4 mfi of toluene and 8 mfi of dimethylformamide at
0°C, followed by stirring for 10 minutes, and 4.0 g (10
mmol) of 4-(2,3,4-trimethoxy-6-methylbenzoyl)-3-methoxy-
5-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-3-
trifluoromethyl-5-methoxypyridine (compound No. 123; m.p.
117-119°C).
SYNTHESIS EXAMPLE 10
Synthesis of 4-(2,3,4-trimethoxy-6-methylbenzoyl)-2-
bromo-3-trifluoromethyl-5-methoxypyridine (compound No.
124)
Using 7.2 g (18 mmol) of 4-(2,3,4-trimethoxy-6-
methylbenzoyl)-3-methoxy-5-trifluoromethylpyridine-N-
oxide, 7 ml of toluene, 17 ml of dimethylformamide and 10
g (35 mmol) of phosphorus oxybromide, 4.1 g (yield 49%)
of 4-(2,3,4-trimethoxy-6-methylbenzoyl)-2-bromo-3-
trifluoromethyl-5-methoxypyridine (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)-2,3,5-
trichloropyridine (compound No. 186)
(a) 17.2 ml (26.7 mmol) of n-butyllithium (1.56 M
hexane solution) was dropwise added to a diethyl ether
(20 mfi) 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. 3 0 mfi 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 (2,3,4-
trimethoxy-6-methylphenyl)(2,3,5-trichloro-4-
pyridyl)methanol.
(b) 16.2 g of manganese dioxide was added to a
toluene (180 mfi) solution of 5.6 g of (2,3,4-trimethoxy-
6-methylphenyl)(2,3,5-trichloro-4-pyridyl)methanol
obtained in step (a), followed by stirring under reflux
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 4.7 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 12
Synthesis of 4-(2,3,4-trimethoxy-6-methylbenzoyl)-3,5-
dichloropyridine (compound No. 191)
4.6 g (6.9 mmoDof triethylamine and 1.8 g of 10%
palladium carbon were added to a methanol 2 80 mfi solution
of 17.8 g (4.6 mmol) of 4-(2,3,4-trimethoxy-6-
methylbenzoyl)-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-6-
methylbenzoyl)-3,5-dichloropyridine (compound No. 191;
m.p. 109-lll°C).
SYNTHESIS EXAMPLE 13
Synthesis of 4-(2,3,4-trimethoxy-6-methylbenzoyl)-3-
chloro-5-methoxypyridine (compound No. 244)
5.0 g (2.8 mmol) of hexamethylphosphoric triamide
and 1.1 g (2.1 mmol) of sodium methoxide were added to a
toluene (60 mfi) solution of 5.0 g (1.4 mmol) of 4-(2,3,4-
trimethoxy-6-methylbenzoyl)-3,5-dichloropyridine
(compound No. 191), followed by stirring under reflux by
heating for 5 hours. After the mixture was cooled, 50 ml
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 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 4-
(2,3,4-trimethoxy-6-methylbenzoyl)-3-chloro-5-
methoxypyridine (compound No. 244; pale yellow oily
substance).
SYNTHESIS EXAMPLE 14
Synthesis of 4-(2,3,4-trimethoxy-6-methylbenzoyl)-2,3-
dichloro-5-methoxypyridine (compound No. 193)
(a) A chloroform (60 mfi) solution of 3.4 g (1 mmol)
of 4-(2,3,4-trimethoxy-6-methylbenzoyl)-3-chloro-5-
methoxypyridine (compound No. 244) was cooled with ice,
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. 3 0 mfi of a 0.5 mol/l 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-6-
methylbenzoyl)-3-chloro-5-methoxypyridine-N-oxide (m.p.
160-166°C).
(b) 5 mfi of dimethylformamide was added to 2.5 mfi of
toluene, the mixture was cooled with ice, and 1.3 mG (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-(2,3,4-
trimethoxy-6-methylbenzoyl)-3-chloro-5-methoxypyridine-N-
oxide was added thereto. After the mixture was stirred
under cooling with ice for 3 0 minutes, the temperature
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
thereto for extraction. The organic layer was dried over
anhydrous sodium sulfate, subjected to filtration and
purified by silica gel column chromatography to obtain
2.0 g (yield 76%) of 4-(2,3,4-trimethoxy-6-
methylbenzoyl)-2,3-dichloro-5-methoxypyridine (compound
No. 193; m.p. 98-99°C) .
SYNTHESIS EXAMPLE 15
Synthesis of 4-(2,3,4-trimethoxy-6-methylbenzoyl)-2bromo-
3-chloro-5-methoxypyridine (compound No. 245)
5 mfi of dimethylformamide was added to 2.5 mfi 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-(2,3,4-
trimethoxy-6-methylbenzoyl)-3-chloro-5-methoxypyridine-N-
oxide obtained in Synthesis Example 14 (a) was added
thereto. After the mixture was stirred under cooling
with ice for 3 0 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-3-
chloro-5-methoxypyridine (compound No. 245; m.p. 97-
99°C).
SYNTHESIS EXAMPLE 16
Synthesis of 4-(2,3,4-trimethoxy-6-methylbenzoyl)-3-
bromo-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 mfi 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-trimethoxy-6-
methylphenyl)(3,5-dibromo-4-pyridyl)methanol (yellow oily
substance).
(b) A tetrahydrofuran (15 mfi) solution of 2.0 g (4.6
mmol) of (2,3,4-trimethoxy-6-methylphenyl)(3,5-dibromo-4-
pyridyl)methanol obtained in step (a) was cooled to
-78°C, 6.0 mfi (9.4 mmol) of n-butyllithium (1.56 M hexane
solution) was dropwise added thereto, followed by
stirring for 5 minutes, and 0.5 mfi (8.0 mmol) of methyl
iodide was added thereto, followed by stirring for 2.5
hours. 20 mfi 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-6-
methylphenyl)(3-bromo-5-methyl-4-pyridyl)methanol.
(c) 3 g of manganese dioxide was added to a toluene
(30 mfi) solution of 0.43 g (1.1 mmol) of (2,3,4-
trimethoxy-6-methylphenyl)(3-bromo-5-methyl-4-
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-(2,3,4-
trimethoxy-6-methylbenzoyl)-3-bromo-5-methylpyridine
(compound No. 228; m.p. 88-93°C).
SYNTHESIS EXAMPLE FOR AN INTERMEDIATE
Now, Synthesis Example of 2,3,4-trimethoxy-6-
methylbenzaldehyde 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 ml) solution of 128 g
(0.7 mol) of 3,4,5-trimethoxytoluene was dropwise added
to a dry methylene chloride 500 mfl 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 16 of ice water, the methylene chloride phase
was separated, and the aqueous phase was extracted with
2 00 mfl of methylene chloride twice. The extract and the
methylene chloride phase were combined together,
sequentially washed with 200 ml of water, 200 mfl of a
saturated aqueous sodium bicarbonate solution and 200 mfl
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
resulting crystal was collected by filtration, washed
with hexane and air dried to obtain 128 g of 2,3,4-
trimethoxy-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 (1-1) 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.
Compounds represented by the formula (X) to 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
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.
The benzoylpyridine derivative represented by the
formula (I) or its salt is useful as an active ingredient
for a fungicide, particularly as an active ingredient for
an agricultural and horticultural fungicide. As the
agricultural and horticultural fungicide, it is effective
for 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 pumila); scab
or black spot of pear (Pyrus serotina, Pyrus ussuriensis,
Pyrus 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 melo); 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
chiloensis); 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
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
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
alkyl aryl phosphoric ester salt or a salt of a
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
ether, an acetylene glycol, an acetylene alcohol, an
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 oil, 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
0.2:99.8 to 90:10. These formulations can be practically
used either as they are or after they are diluted with a
diluent such as water to predetermined concentrations and
a spreading agent is added thereto as the case requires.
The concentration of the compound of the present
invention varies depending upon the crop plant as the
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,
atomizing, 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%
of 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) of
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, Propoxur,
Aldicarb, Carbofuran, Thiodicarb, Methomyl, Oxamyl,
Ethiofencarb, Pirimicarb, Fenobucarb, Carbosulfan and
Benfuracarb;
nelicetoxin derivatives such as Cartap and
Thiocyclam;
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,
Triazamate, Pymetrozine, Pyrimidifen, Chlorfenapyr,
Indoxacarb, Acequinocyl, Etoxazole, Cyromazine and 1,3-
dichloropropene; 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, Myclobutanil, Cyproconazole,
Terbuconazole, Hexaconazole, Furconazole-cis, Prochloraz,
Metconazole, Epoxiconazole, Tetraconazole, Oxpoconazole
fumarate and Sipconazole;
quinoxaline type compounds such as Quinomethionate;
dithiocarbamate type compounds such as Maneb, Zineb,
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 Cyazofamid;
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, O-
diisopropylphosphorothioate, O-ethyl S,S-
diphenylphosphorodithioate 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;
urea type compounds such as Pencycuron;
cinnamic acid type compounds such as Dimethomorph;
phenyl carbamate type compounds such as
Diethofencarb;
cyanopyrrole type compounds such as Fludioxonil and
Fenpiclonil;
strobilurin type compounds such as Azoxystrobin,
Kresoxim-Methyl, Metominofen, Triflouxystrobin,
Picoxystrobin and Pyraclostrobin: (BAS 500F);
oxazolidinone type compounds such as Famoxadone; thiazole
carboxamide type compounds such as Ethaboxam;
silyl amide type compounds such as Silthiopham;
aminoacid amidecarbamate 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
BJL-993, BJL-994, BAS-510, BAS-505, MTF-753 andUIBF-307.
Now, Test Examples of the agricultural and
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]
5 : No lesions nor sporogony recognizable
4 : Area of lesions, number of lesions or area of
sporogony is less than 10% of non-treated plot
3 : Area of lesions, number of lesions or area of
sporogony is less than 40% of non-treated plot
2 : Area of lesions, number of lesions or area of
sporogony is less than 70% of non-treated plot
1 : Area of lesions, number of lesions or area of
sporogony is at least 70% of non-treated plot
TEST EXAMPLE 1
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 2 0°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, 114, 117, 119, 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, 35, 36,
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, 123,
124, 133, 136, 142, 186, 187, 188, 189, 190, 191, 192,
193, 194, 199, 200, 210, 211, 213, 228, 243, 245, 249,
252, 254, 272, 287, 288, 289, 290, 291 and 292 showed
effects with a controlling index of 4 or above at a
concentration of 12 5 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, and 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 for 24 hours,
and then kept in a thermostatic chamber at 2 0°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
12 5 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 ml 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
the compounds Nos. 9, 11, 55, 90 and 102 showed effects
with a controlling index of 4 or above at a concentration
of 12 5 ppm.
TEST EXAMPLE 4
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 ml 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 cucumber was sprayed and inoculated
with a conidiospore suspension of fungi of powdery
mildew, and the cucumber was kept in a thermostatic
chamber at 2 0 °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 4 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 12 5 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.
FORMULATION EXAMPLE 1
(1) Compound of the present invention
20 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
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
2 0 parts by weight
(2) N,N'-dimethylacetamide 2 0 parts by weight
(3) Polyoxyethylene alkyl phenyl ether
10 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
5 parts by weight
(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
50 parts by weight
(2) Oxylated polyalkylphenyl phosphate-
triethanolamine 2 parts by weight
(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.
FORMULATION EXAMPLE 6
(1) Compound of the present invention
5 parts by weight
(2) Polyoxyethylene octylphenyl ether
1 part by weight
(3) Phosphate of polyoxyethylene
0.1 part by weight
(4) Particulate calcium carbonate
93.9 parts by weight
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 9 5.0 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
2 0 parts by weight
(2) Oxylated polyalkylphenol phosphate
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
represented by the formula (I) or its salt has excellent
effects as an active ingredient of a fungicide.
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 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.

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in-pct-2002-1520-kol-granted-claims.pdf

in-pct-2002-1520-kol-granted-correspondence.pdf

in-pct-2002-1520-kol-granted-description (complete).pdf

in-pct-2002-1520-kol-granted-examination report.pdf

in-pct-2002-1520-kol-granted-form 1.pdf

in-pct-2002-1520-kol-granted-form 13.pdf

in-pct-2002-1520-kol-granted-form 18.pdf

in-pct-2002-1520-kol-granted-form 2.pdf

in-pct-2002-1520-kol-granted-form 3.pdf

in-pct-2002-1520-kol-granted-form 5.pdf

in-pct-2002-1520-kol-granted-gpa.pdf

in-pct-2002-1520-kol-granted-priority document.pdf

in-pct-2002-1520-kol-granted-reply to examination report.pdf

in-pct-2002-1520-kol-granted-specification.pdf

in-pct-2002-1520-kol-granted-translated copy of priority document.pdf

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Patent Number

225673

Indian Patent Application Number

IN/PCT/2002/1520/KOL

PG Journal Number

47/2008

Publication Date

21-Nov-2008

Grant Date

19-Nov-2008

Date of Filing

12-Dec-2002

Name of Patentee

ISHIHARA SANGYO KAISHA, LTD.

Applicant Address

3-15, EDOBORI 1-CHOME, NISHI-KU, OSAKA-SHI, OSAKA 550-0002

Inventors:

#	Inventor's Name	Inventor's Address
1	NISHIDE HISAYA	C/O ISHIHARA SANGYO KAISHA LTD. CHUO KEN-KYUSHO, 3-1, NISHI-SHIBUKAWA 2-CHOME, KUSATSU-SHI, SHIGA 525-0025
2	OGAWA MUNEKAZU	C/O ISHIHARA SANGYO KAISHA LTD. CHUO KEN-KYUSHO, 3-1, NISHI-SHIBUKAWA 2-CHOME, KUSATSU-SHI, SHIGA 525-0025
3	KOMINAMI HIDEMASA	C/O ISHIHARA SANGYO KAISHA LTD. CHUO KEN-KYUSHO, 3-1, NISHI-SHIBUKAWA 2-CHOME, KUSATSU-SHI, SHIGA 525-0025
4	HIGUCHI KOJI	C/O ISHIHARA SANGYO KAISHA LTD. CHUO KEN-KYUSHO, 3-1, NISHI-SHIBUKAWA 2-CHOME, KUSATSU-SHI, SHIGA 525-0025
5	NISHIMURA AKIHIRO	C/O ISHIHARA SANGYO KAISHA LTD. CHUO KEN-KYUSHO, 3-1, NISHI-SHIBUKAWA 2-CHOME, KUSATSU-SHI, SHIGA 525-0025

PCT International Classification Number

C07D 213/61

PCT International Application Number

PCT/JP01/05851

PCT International Filing date

2001-07-05

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	2001-094222	2001-03-28	Japan
2	2000-203909	2000-07-05	Japan
3	2001-034182	2001-02-09	Japan