Substituted aromatic amide derivative, intermediate thereof, agrohorticultural insecticide containing thereof and method for the use thereof

This application is the national phase of international application PCT/JP02/04742 filed 16 May 2002 which designated the U.S.

The present invention relates to a substituted aromatic amide derivative, an intermediate thereof, an agrohorticultural insecticide containing said substituted aromatic amide derivative as an active ingredient, and a method for the use thereof.

Although JP-A-11-240857, JP-A-2001-131141, JP-A-2001-64258 and JP-A-2001-64268 disclose compounds which are considered analogous to the compound of the present invention, these patent gazettes neither disclose nor suggest the compounds which are represented by the general formula (I) of the present invention.

In the field of crop production such as agriculture, horticulture, etc., great injuries are done by pest insects even today, and development of a novel agrohorticultural insecticide is earnestly awaited, especially considering the appearance of resistant pest insecticides to the existing insecticides. At the same time, the age of agricultural workers becomes higher year by year, which makes it necessary to think out various labor-economizing methods of pesticide application and to create an agrohorticultural insecticide suitable for such new application methods.

The present inventors have conducted extensive studies with the aim of developing a novel agrohorticultural insecticide. As a result, it has been found that the fluoroalkyl-substituted aromatic amine derivatives represented by general formula (IV), which are new compounds not found in literature, are useful as an intermediate for the manufacture of various physiologically active derivatives such as medical drugs, pesticides, etc. Further, it has also been found that the substituted aromatic amide derivatives represented by general formula (I) derived from the above-mentioned compounds are new compounds not found in literature; and they exhibit an excellent insecticidal effect at a low dosage as compared with prior compounds found in literature, and exhibit high uptake and translocation from the root and an excellent insecticidal effect especially when applied to soil. Based on these findings, this invention has been accomplished.

Thus, the present invention relates to a substituted aromatic amide derivative represented by the following general formula (I):

{wherein Z represents formula (II):

(wherein A, R 1 and R 2 are as defined below), or formula (III):

(wherein A represents a C 1 -C 6 alkylene group; a substituted C 1 -C 6 alkylene group having at least one, the same or different substituents selected from the group consisting of halogen atom, cyano group, nitro group, halo C 1 -C 6 alkyl group, C 1 -C 6 alkoxy group, halo C 1 -C 6 alkoxy group, C 1 -C 6 alkylthio group, halo C 1 -C 6 alkylthio group, C 1 -C 6 alkylsulfinyl group, halo C 1 -C 6 alkylsulfinyl group, C 1 -C 6 alkylsulfonyl group, halo C 1 -C 6 alkylsulfonyl group, C 1 -C 6 alkylthio C 1 -C 6 alkyl group, C 1 -C 6 alkoxycarbonyl group and phenyl group; a C 2 -C 6 alkenylene group; a substituted C 2 -C 6 alkenylene group having at least one, the same or different substituents selected from the group consisting of halogen atom, cyano group, nitro group, halo C 1 -C 6 alkyl group, C 1 -C 6 alkoxy group, halo C 1 -C 6 alkoxy group, C 1 -C 6 alkylthio group, halo C 1 -C 6 alkylthio group, C 1 -C 6 alkylsulfinyl group, halo C 1 -C 6 alkylsulfinyl group, C 1 -C 6 alkylsulfonyl group, halo C 1 -C 6 alkylsulfonyl group, C 1 -C 6 alkylthio C 1 -C 6 alkyl group, C 1 -C 6 alkoxycarbonyl group and phenyl group; a C 2 -C 6 alkynylene group; or a substituted C 3 -C 6 alkynylene group having at least one, the same or different substituents selected from the group consisting of halogen atom, cyano group, nitro group, halo C 1 -C 6 alkyl group, C 1 -C 6 alkoxy group, halo C 1 -C 6 alkoxy group, C 1 -C 6 alkylthio group, halo C 1 -C 6 alkylthio group, C 1 -C 6 alkylsulfinyl group, halo C 1 -C 6 alkylsulfinyl group, C 1 -C 6 alkylsulfonyl group, halo C 1 -C 6 alkylsulfonyl group, C 1 -C 6 alkylthio C 1 -C 6 alkyl group, C 1 -C 6 alkoxycarbonyl group and phenyl group; and an arbitrarily selected saturated carbon atom in the C 1 -C 6 alkylene group, substituted C 1 -C 6 alkylene group, C 3 -C 6 alkenylene group, substituted C 3 -C 6 alkenylene group, C 3 -C 6 alkynylene group or substituted C 3 -C 6 alkynylene group may be substituted with a C 2 -C 5 alkylene group to form a C 3 -C 6 cycloalkane ring, and arbitrarily selected two carbon atoms in the C 2 -C 6 alkylene group, substituted C 2 -C 6 alkylene group, C 3 -C 6 alkenylene group or substituted C 3 -C 6 alkenylene group may be taken conjointly together with an alkylene group or an alkenylene group to form a C 3 -C 6 cycloalkane ring or a C 3 -C 6 cycloalkene ring;

R 1 represents a hydrogen atom; a halogen atom; a cyano group; a nitro group; a C 3 -C 6 cycloalkyl group; a C 1 -C 6 alkoxycarbonyl group; a mono C 1 -C 6 alkylaminocarbonyl group; a di C 1 -C 6 alkylaminocarbonyl group which the C 1 -C 6 alkyl groups may be the same or different; a mono C 1 -C 6 alkylaminosulfonyl group; a di C 1 -C 6 alkylaminosulfonyl group which the C 1 -C 6 alkyl groups may be the same or different; a di C 1 -C 6 alkoxyphosphoryl group which the C 1 -C 6 alkyl groups may be the same or different; a di C 1 -C 6 alkoxythiophosphoryl group which the C 1 -C 6 alkyl groups may be the same or different; —C(R 5 )═NOR 6 (in this formula, R 5 represents a hydrogen atom or a C 1 -C 6 alkyl group; and R 6 represents a hydrogen atom; a C 1 -C 6 alkyl group; a C 3 -C 6 alkenyl group; a C 3 -C 6 alkynyl group; a C 3 -C 6 cycloalkyl group; a phenyl C 1 -C 4 alkyl group; or a substituted phenyl C 1 -C 4 alkyl group having, on the ring thereof, at least one, the same or different substituents selected from the group consisting of halogen atom, C 1 -C 6 alkyl group, halo C 1 -C 6 alkyl group, C 1 -C 6 alkoxy group and C 1 -C 6 alkylthio group); a phenyl group; a substituted phenyl group having at least one, the same or different substituents selected from the group consisting of halogen atom, cyano group, nitro group, C 1 -C 6 alkyl group, halo C 1 -C 6 alkyl group, C 1 -C 6 alkoxy group, halo C 1 -C 6 alkoxy group, C 1 -C 6 alkylthio group, halo C 1 -C 6 alkylthio group, C 1 -C 6 alkylsulfinyl group, halo C 1 -C 6 alkylsulfinyl group, C 1 -C 6 alkylsulfonyl group and halo C 1 -C 6 alkylsulfonyl group; a heterocyclic group; a substituted heterocyclic group having at least one, the same or different substituents selected from the group consisting of halogen atom, cyano group, nitro group, C 1 -C 6 alkyl group, halo C 1 -C 6 alkyl group, C 1 -C 6 alkoxy group, halo C 1 -C 6 alkoxy group, C 1 -C 6 alkylthio group, halo C 1 -C 6 alkylthio group, C 1 -C 6 alkylsulfinyl group, halo C 1 -C 6 alkylsulfinyl group, C 1 -C 6 alkylsulfonyl group and halo C 1 -C 6 alkylsulfonyl group; or -A 1 -R 7 (in this formula, A 1 represents —O—, —S—, —SO—, —SO 2 — or —N(R 6 )— (in this formula, R 6 is as defined above); and R 7 represents a hydrogen atom; a C 1 -C 6 alkyl group; a halo C 1 -C 6 alkyl group; a C 3 -C 6 alkenyl group; a halo C 3 -C 6 alkenyl group; a C 3 -C 6 alkynyl group; a halo C 3 -C 6 alkynyl group; a C 3 -C 6 cycloalkyl group; a phenyl group; a substituted phenyl group having at least one, the same or different substituents selected from the group consisting of halogen atom, cyano group, nitro group, C 1 -C 6 alkyl group, halo C 1 -C 6 alkyl group, C 1 -C 6 alkoxy group, halo C 1 -C 6 alkoxy group, C 1 -C 6 alkylthio group, halo C 1 -C 6 alkylthio group, C 1 -C 6 alkylsulfinyl group, halo C 1 -C 6 alkylsulfinyl group, C 1 -C 6 alkylsulfonyl group, halo C 1 -C 6 alkylsulfonyl group and C 1 -C 6 alkoxycarbonyl group; a phenyl C 1 -C 4 alkyl group; a substituted phenyl C 1 -C 4 alkyl group having, on the ring thereof, at least one, the same or different substituents selected from the group consisting of halogen atom, cyano group, nitro group, C 1 -C 6 alkyl group, halo C 1 -C 6 alkyl group, C 1 -C 6 alkoxy group, halo C 1 -C 6 alkoxy group, C 1 -C 6 alkylthio group, halo C 1 -C 6 alkylthio group, C 1 -C 6 alkylsulfinyl group, halo C 1 -C 6 alkylsulfinyl group, C 1 -C 6 alkylsulfonyl group, halo C 1 -C 6 alkylsulfonyl group and C 1 -C 6 alkoxycarbonyl group; a heterocyclic group; a substituted heterocyclic group having, on the ring thereof, at least one, the same or different substituents selected from the group consisting of halogen atom, cyano group, nitro group, C 1 -C 6 alkyl group, halo C 1 -C 6 alkyl group, C 1 -C 6 alkoxy group, halo C 1 -C 6 alkoxy group, C 1 -C 6 alkylthio group, halo C 1 -C 6 alkylthio group, C 1 -C 6 alkylsulfinyl group, halo C 1 -C 6 alkylsulfinyl group, C 1 -C 6 alkylsulfonyl group, halo C 1 -C 6 alkylsulfonyl group and C 1 -C 6 alkoxycarbonyl group; a C 1 -C 6 alkylcarbonyl group; a halo C 1 -C 6 alkylcarbonyl group; a C 1 -C 6 alokoxycarbonyl group; a mono C 1 -C 6 alkylaminocarbonyl group; a di C 1 -C 6 alkylaminocarbonyl group which the C 1 -C 6 alkyl groups may be the same or different; a C 1 -C 6 alkylsulfonyl group; a halo C 1 -C 6 alkylsulfonyl group; a mono C 1 -C 6 alkylaminosulfonyl group; a di C 1 -C 6 alkylaminosulfonyl group which the C 1 -C 6 alkyl groups may be the same or different; a di C 1 -C 6 alkoxyphosphoryl group which the C 1 -C 6 alkyl groups may be the same or different; or a di C 1 -C 6 alkoxythiophosphoryl group which the C 1 -C 6 alkyl groups may be the same or different);

R 2 represents a hydrogen atom; a C 1 -C 4 alkyl group; a C 1 -C 4 alkoxy C 1 -C 4 alkyl group; or a C 1 -C 4 alkylthio C 1 -C 4 alkyl group; and R 2 may be taken conjointly together with A or R 1 to form one to three, the same or different, 5- to 7-membered rings which may be intercepted by oxygen atom, sulfur atom or nitrogen atom);

R 3 represents a hydrogen atom; a C 1 -C 4 alkyl group; a C 1 -C 4 alkoxy C 1 -C 4 alkyl group; or a C 1 -C 4 alkylthio C 1 -C 4 alkyl group;

R 4 represents a hydrogen atom; a fluorine atom; or a fluoro C 1 -C 6 alkyl group; and Rf represents a fluorine atom; or a fluoro C 1 -C 6 alkyl group;

Q 1 to Q 9 , which may be the same or different, represent a carbon atom or a nitrogen atom;

X which may be the same or different represent a halogen atom; a nitro group; a cyano group; a C 1 -C 6 alkyl group; a halo C 1 -C 6 alkyl group; a C 2 -C 6 alkenyl group; a halo C 2 -C 6 alkenyl group; a C 2 -C 6 alkynyl group; a halo C 2 -C 6 alkynyl group; a C 1 -C 6 alkoxy group; a halo C 1 -C 6 alkoxy group; a C 1 -C 6 alkylthio group; a halo C 1 -C 6 alkylthio group; a C 1 -C 6 alkylsulfinyl group; a halo C 1 -C 6 alkylsulfinyl group; a C 1 -C 6 alkylsulfonyl group; or a halo C 1 -C 6 alkylsulfonyl group; and two groups of X residing in adjacent positions on the aromatic ring may be taken conjointly to form a fused ring, and said fused ring may have at least one, the same or different substituents selected from the group consisting of halogen atom, cyano group, nitro group, C 1 -C 6 alkyl group, halo C 1 -C 6 alkyl group, C 1 -C 6 alkoxy group, halo C 1 -C 6 alkoxy group, C 1 -C 6 alkylthio group, halo C 1 -C 6 alkylthio group, C 1 -C 6 alkylsulfinyl group, halo C 1 -C 6 alkylsulfinyl group, C 1 -C 6 alkylsulfonyl group and halo C 1 -C 6 alkylsulfonyl group; and 1 represents an integer of 0 to 2;

Y which may be the same or different represents a halogen atom; a C 1 -C 6 alkyl group; a halo C 1 -C 6 alkyl group; a cyclo C 3 -C 6 alkyl group; a C 1 -C 6 alkoxy group; a halo C 1 -C 6 alkoxy group; a mono C 1 -C 6 alkylamino group; a di C 1 -C 6 alkylamino group which the C 1 -C 6 alkyl groups may be the same or different, a C 1 -C 6 alkylthio group; a halo C 1 -C 6 alkylthio group; a C 1 -C 6 alkylsulfinyl group; a halo C 1 -C 6 alkylsulfinyl group; a C 1 -C 6 alkylsulfonyl group; a halo C 1 -C 6 alkylsulfonyl group; a phenyl group; a substituted phenyl group having at least one, the same or different substituents selected from the group consisting of halogen atom, C 1 -C 6 alkyl group, halo C 1 -C 6 alkyl group, C 1 -C 6 alkoxy group, halo C 1 -C 6 alkoxy group, C 1 -C 6 alkylthio group, halo C 1 -C 6 alkylthio group, C 1 -C 6 alkylsulfinyl group, halo C 1 -C 6 alkylsulfinyl group, C 1 -C 6 alkylsulfonyl group and halo C 1 -C 6 alkylsulfonyl group; a phenyl C 1 -C 4 alkyl group; a substituted phenyl C 1 -C 4 alkyl group having, on the ring thereof, at least one, the same or different substituents selected from the group consisting of halogen atom, C 1 -C 6 alkyl group, halo C 1 -C 6 alkyl group, C 1 -C 6 alkoxy group, halo C 1 -C 6 alkoxy group, C 1 -C 6 alkylthio group, halo C 1 -C 6 alkylthio group, C 1 -C 6 alkylsulfinyl group, halo C 1 -C 6 alkylsulfinyl group, C 1 -C 6 alkylsulfonyl group and halo C 1 -C 6 alkylsulfonyl group; a phenoxy group; a substituted phenoxy group having at least one, the same or different substituents selected from the group consisting of halogen atom, C 1 -C 6 alkyl group, halo C 1 -C 6 alkyl group, C 1 -C 6 alkoxy group, halo C 1 -C 6 alkoxy group, C 1 -C 6 alkylthio group, halo C 1 -C 6 alkylthio group, C 1 -C 6 alkylsulfinyl group, halo C 1 -C 6 alkylsulfinyl group, C 1 -C 6 alkylsulfonyl group and halo C 1 -C 6 alkylsulfonyl group; a phenylthio group; a substituted phenylthio group having at least one, the same or different substituents selected from the group consisting of halogen atom, C 1 -C 6 alkyl group, halo C 1 -C 6 alkyl group, C 1 -C 6 alkoxy group, halo C 1 -C 6 alkoxy group, C 1 -C 6 alkylthio group, halo C 1 -C 6 alkylthio group, C 1 -C 6 alkylsulfinyl group, halo C 1 -C 6 alkylsulfinyl group, C 1 -C 6 alkylsulfonyl group and halo C 1 -C 6 alkylsulfonyl group; a heterocyclic group; or a substituted heterocyclic group having at least one, the same or different substituents selected from the group consisting of halogen atom, cyano group, nitro group, C 1 -C 6 alkyl group, halo C 1 -C 6 alkyl group, C 1 -C 6 alkoxy group, halo C 1 -C 6 alkoxy group, C 1 -C 6 alkylthio group, halo C 1 -C 6 alkylthio group, C 1 -C 6 alkylsulfinyl group, halo C 1 -C 6 alkylsulfinyl group, C 1 -C 6 alkylsulfonyl group and halo C 1 -C 6 alkylsulfonyl group; and two groups of Y residing in adjacent positions on the aromatic ring may be taken conjointly to form a fused ring, and said fused ring may have at least one, the same or different substituents selected from the group consisting of halogen atom, C 1 -C 6 alkyl group, halo C 1 -C 6 alkyl group, C 1 -C 6 alkoxy group, halo C 1 -C 6 alkoxy group, C 1 -C 6 alkylthio group, halo C 1 -C 6 alkylthio group, C 1 -C 6 alkylsulfinyl group, halo C 1 -C 6 alkylsulfinyl group, C 1 -C 6 alkylsulfonyl group and halo C 1 -C 6 alkylsulfonyl group; and

Y may be taken conjointly together with R 3 to form a 5- to 7-membered ring which may be intercepted by one or two, the same or different oxygen atoms, sulfur atoms or nitrogen atoms; and m represents an integer of 0 to 3}, an agrohorticultural insecticide containing said compound as an active ingredient and a method for using the same.

The present invention further relates to a fluoroalkyl-substituted aromatic amine derivative represented by general formula (IV):

(wherein R 3 represents a hydrogen atom; a C 1 -C 4 alkyl group; a C 1 -C 4 alkoxy C 1 -C 4 alkyl group; or a C 1 -C 4 alkylthio C 1 -C 4 alkyl group; R 4 represents a hydrogen atom; a fluorine atom; or a fluoro C 1 -C 6 alkyl group; and Rf represents a fluorine atom; or a fluoro C 1 -C 6 alkyl group;

Q 5 to Q 9 which may be the same or different represent a carbon atom or a nitrogen atom;

Y which may be the same or different represents a halogen atom; a C 1 -C 6 alkyl group; a halo C 1 -C 6 alkyl group; a C 1 -C 6 alkoxy group; a halo C 1 -C 6 alkoxy group; a C 1 -C 6 alkylthio group; a halo C 1 -C 6 alkylthio group; a C 1 -C 6 alkylsulfinyl group; a halo C 1 -C 6 alkylsulfinyl group; a C 1 -C 6 alkylsulfonyl group; a halo C 1 -C 6 alkylsulfonyl group; a phenyl group; a substituted phenyl group having at least one, the same or different substituents selected from the group consisting of halogen atom, C 1 -C 6 alkyl group, halo C 1 -C 6 alkyl group, C 1 -C 6 alkoxy group, halo C 1 -C 6 alkoxy group, C 1 -C 6 alkylthio group, halo C 1 -C 6 alkylthio group, C 1 -C 6 alkylsulfinyl group, halo C 1 -C 6 alkylsulfinyl group, C 1 -C 6 alkylsulfonyl group and halo C 1 -C 6 alkylsulfonyl group; a phenyl C 1 -C 4 alkyl group; a substituted phenyl C 1 -C 4 alkyl group having, on the ring thereof, at least one, the same or different substituents selected from the group consisting of halogen atom, C 1 -C 6 alkyl group, halo C 1 -C 6 alkyl group, C 1 -C 6 alkoxy group, halo C 1 -C 6 alkoxy group, C 1 -C 6 alkylthio group, halo C 1 -C 6 alkylthio group, C 1 -C 6 alkylsulfinyl group, halo C 1 -C 6 alkylsulfinyl group, C 1 -C 6 alkylsulfonyl group and halo C 1 -C 6 alkylsulfonyl group; a phenoxy group; or a substituted phenoxy group having at least one, the same or different substituents selected from the group consisting of halogen atom, C 1 -C 6 alkyl group, halo C 1 -C 6 alkyl group, C 1 -C 6 alkoxy group, halo C 1 -C 6 alkoxy group, C 1 -C 6 alkylthio group, halo C 1 -C 6 alkylthio group, C 1 -C 6 alkylsulfinyl group, halo C 1 -C 6 alkylsulfinyl group, C 1 -C 6 alkylsulfonyl group and halo C 1 -C 6 alkylsulfonyl group; and two groups of Y residing in the adjacent positions on the aromatic ring may be taken conjointly to form a fused ring, and said fused ring may have at least one, the same or different substituents selected from the group consisting of halogen atom, C 1 -C 6 alkyl group, halo C 1 -C 6 alkyl group, C 1 -C 6 alkoxy group, halo C 1 -C 6 alkoxy group, C 1 -C 6 alkylthio group, halo C 1 -C 6 alkylthio group, C 1 -C 6 alkylsulfinyl group, halo C 1 -C 6 alkylsulfinyl group, C 1 -C 6 alkylsulfonyl group and halo C 1 -C 6 alkylsulfonyl group; and m represents an integer of 0 to 3;

provided that when m represents an integer of 0, then R 4 is not a hydrogen atom or R 4 and Rf do not simultaneously represent a fluorine atom);

which is an intermediate compound for manufacture of the above-mentioned substituted aromatic amine derivative.

In the definition of general formula (I) representing the substituted aromatic amide derivatives of this invention, the term “halogen atom” means a chlorine atom, a bromine atom, an iodine atom or a fluorine atom; “n-” means normal, “s-” means secondary and “t-” means tertiary; “C 1 -C 6 alkyl” means a straight or branched chain alkyl group having 1 to 6 carbon atoms such as methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, n-pentyl, neopentyl, n-hexyl and the like; “C 1 -C 6 haloalkyl” means a straight or branched chain alkyl group having 1 to 6 carbon atoms which is substituted with at least one, the same or different halogen atoms, such as trifluoromethyl group, difluoromethyl group, perfluoroethyl group, perfluoroisopropyl group, chloromethyl group, bromomethyl group, 1-bromoethyl group, 2,3-dibromopropyl group and the like; “C 1 -C 6 alkylene” means a straight or branched chain alkylene group having 1 to 6 carbon atoms such as methylene, ethylene, propylene, trimethylene, dimethylmethylene, tetramethylene, isobutylene, dimethylethylene, hexamethylene and the like; and “C 2 -C 6 alkenylene” or “C 2 -C 6 alkynylene” similarly means a straight or branched chain alkenylene or alkynylene group having 2 to 6 carbon atoms; “C 3 -C 6 cycloalkyl” means an alicyclic alkyl group having 3-6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like.

As the “heterocyclic group”, mention can be made of, for example, pyridyl group, pyridine-N-oxide group, pyrimidinyl group, furyl group, tetrahydrofuryl group, thienyl group, tetrahydrothienyl group, tetrahydropyranyl group, tetrahydrothiopyranyl group, oxazolyl group, isoxazolyl group, oxadiazolyl group, thiazolyl group, isothiazolyl group, thiadiazolyl group, imidazolyl group, triazolyl group, pyrazolyl group and the like. As the “fused ring”, mention can be made of, for example, naphthalene, tetrahydronaphthalene, indene, indane, quinoline, quinazoline, indole, indoline, chroman, isochroman, benzodioxane, benzodioxole, benzofuran, dihydrobenzofuran, benzothiophene, dihydrobenzothiophene, benzoxazole, benzothiazole, benzimidazole, indazole, and the like.

In some cases, the substituted aromatic amide derivative represented by general formula (I) may have one or plural asymmetric carbon atoms or asymmetric centers in the structural formula thereof and may have two or more optical isomers and diastereomers. In such cases, the present invention involves all such optical isomers and mixtures of such optical isomers at any proportions. Further, in some cases, the substituted aromatic amide derivative represented by general formula (I) of the present invention may have two geometrical isomers due to carbon-carbon double bond or carbon-nitrogen double bond in the structural formula thereof. In such a case, the present invention involves all such geometrical isomers and mixtures of such geometrical isomers in any proportions.

In the substituted aromatic amide derivatives represented by general formula (I) of the present invention, A is preferably a C 1 -C 6 alkylene group and further preferably a C 3 -C 6 alkylene group; R 1 is preferably a hydrogen atom or a group -A 1 -R 7 and further preferably A 1 -A 7 in which A 1 is S, SO or SO 2 and R 7 is a C 1 -C 6 alkyl group. R 2 is preferably a hydrogen atom or a C 1 -C 4 alkyl group, and further preferably a hydrogen atom; R 3 is preferably a hydrogen atom or a C 1 -C 4 alkyl group, and further preferably a hydrogen atom; R 4 is preferably a hydrogen atom or a fluoro C 1 -C 6 alkyl group, and further preferably a fluoro C 1 -C 3 alkyl group; Rf is preferably a fluoro C 1 -C 6 alkyl group, and further preferably a C 1 -C 3 alkyl group; Q 1 to Q 9 represent a carbon atom or a nitrogen atom, and further preferably Q 1 to Q 5 and Q 7 to Q 9 represent a carbon atom and Q 6 is a carbon atom or a nitrogen atom; X is preferably a halogen atom, and further preferably an iodine atom; 1 preferably represents 1; Y is preferably a halogen atom or a C 1 -C 6 alkyl group, and further preferably a methyl group; and m preferably represents 1.

The substituted aromatic amide derivatives represented by general formula (I) and the fluoroalkyl-substituted aromatic amine derivatives represented by general formula (IV) can be produced from the fluoroalkyl-substituted aromatic amine derivatives represented by general formula (IV) which can be produced according to the process disclosed in, for instance, in JP-A-11-302233, European Patent No. 1006102, etc., according to the process scheme shown below, for example. It is also possible, however, to produce the substituted aromatic amide derivatives of general formula (I) according to the processes disclosed in JP-A-11-240857, JP-A-2001-131141, JP-A-2001-64258, JP-A-2001-64268, etc.

wherein R 1 , R 2 , R 3 , R 4 , Rf, Y, m, X, l, Q 1 , Q 2 , Q 3 , Q 4 , Q 5 , Q 6 , Q 7 , Q 8 and Q 9 are as defined above.

A fluoroalkyl-substituted aromatic amine represented by general formula (V) is subjected to a reduction in the presence or absence of an inert solvent, in the presence of a reducing agent to form a fluoroalkyl-substituted aromatic amine derivative represented by general formula (IV). After isolating or not isolating said fluoroalkyl-substituted aromatic amine derivative, it is reacted with a phthalic acid isoimide represented by general formula (VI), whereby a substituted aromatic amide derivative represented by general formula (I-1) can be obtained.

1-1. General Formula (V)→General Formula (IV)

As the reducing agent used in this reaction, for example, metal hydrides such as lithium aluminum hydride, sodium bis(2-methoxyethoxy)aluminum hydride, sodium borohydride and the like, metals such as metallic lithium and the like, and metallic salts can be referred to, and the amount of the reducing agent may be appropriately selected from a range of from an equivalent amount to an excessive amount based on the fluoroalkyl-substituted aromatic amine represented by general formula (V).

The solvent used in this reaction may be any solvent so far as the solvent does not disturb the progress of this reaction markedly, and examples of such a solvent include aromatic hydrocarbons such as benzene, toluene, xylene and the like, halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride and the like, halogenated aromatic hydrocarbons such as chlorobenzene, dichlorobenzene and the like, acyclic and cyclic ethers such as diethyl ether, dioxane, tetrahydrofuran and the like, etc. These inert solvents may be used either alone or in the form of a mixture of two or more.

The reaction can be carried out at a temperature ranging from room temperature to the boiling temperature of the used inert solvent. Although the reaction time varies depending on the scale and temperature of the reaction, it is in the range of from several minutes to 50 hours.

After completion of the reaction, the product is isolated from the reaction system containing the objective compound in the conventional method. The objective compound can be produced by purification such as recrystallization, column chromatography, etc., according to the need. It is also possible to feed the objective compound to the next step of the reaction, without isolation from the reaction system.

1-2. General Formula (IV)→General Formula (I-1)

The fluoroalkyl-substituted aromatic amine derivative of general formula (IV) is reacted with a phthalic acid isoimide represented by general formula (VI) in the presence of an inert solvent, whereby a substituted aromatic amide derivative represented by general formula (I-1) can be obtained.

This reaction may be carried out in the presence of an acid or a base, of which amount may be varied in the range from a catalytic amount to an excessive amount according to the need.

As the inert solvent used in this reaction, any solvent may be used so far as the solvent does not disturb the progress of the reaction markedly. Examples of the inert solvent include aromatic hydrocarbons such as benzene, toluene, xylene and the like; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride and the like; halogenated aromatic hydrocarbons such as chlorobenzene, dichlorobenzene and the like; acyclic and cyclic ethers such as diethyl ether, dioxane, tetrahydrofuran and the like; esters such as ethyl acetate and the like; nitrites such as acetonitrile and the like; amides such as dimethylformamide, dimethylacetamide and the like; acids such as acetic acid and the like; dimethyl sulfoxide; 1,3-dimethyl-2-imidazolidinone; etc. These inert solvents may be used either alone or in the form of a mixture of two or more.

Since this reaction is an equimolar reaction, the reactants may be used in equimolar amounts. It is also possible to use any one of the reactants in an excessive amount. If desired, the reaction may be carried out under a dehydrating condition.

The reaction can be carried out at a temperature ranging from room temperature to the boiling temperature of the used inert solvent.

Although the reaction time varies depending on the scale and temperature of the reaction, it is in the range of from several minutes to 48 hours.

After completion of the reaction, the product is isolated from the reaction system containing the objective compound in the conventional method. The objective compound can be produced by purification such as recrystallization, column chromatography, etc., according to the need.

In the case that R 1 represents -A 1 -R 7 in the general formula (I-1), the compound wherein A 1 is —SO— or —SO 2 — can be prepared from the compound wherein A 1 is —S— by the usual method, for example, an oxidation of the compound wherein A 1 is —S— with the oxidizing agent such as m-chloroperbenzoic acid.

The phthalic acid isoimide represented by general formula (VI) can be produced according to the method described in, for example, J. Med. Chem., 10, 982 (1967).

wherein A, R 1 , R 2 , R 3 , R 4 , Rf, X, l, Y, m, Q 1 , Q 2 , Q 3 , Q 4 , Q 5 , Q 6 , Q 7 , Q 8 and Q 9 are as defined above, and M represents a halogen atom or R 8 SO 3 − wherein R 8 represents a C 1 -C 6 alkyl group such as methyl group or the like or a phenyl group which may have a substituent such as methyl group or the like on the para position thereof.

A diamide represented by general formula (VIII) is reacted with a halogenating agent or a sulfonic ester-forming agent in the presence or absence of an inert solvent to form a compound represented by general formula (VII), and then the compound (VII) is subjected to a cyclization reaction under a heating condition or by the use of a base or the like, whereby a substituted aromatic amide derivative represented by general formula (I-2) can be obtained.

2-1. General Formula (VIII)→General Formula (VII)

As the halogenating agents which can be used in this reaction, diethylamino sulfur trifluoride (DAST), thionyl chloride, phosphorus oxychloride, and combination of triphenylphosphine and carbon tetrabromide or carbon tetrachloride can be referred to. As the sulfonic acid-forming agents which can be used, sulfonic acid halides such as methaneuslfonyl chloride, p-toluenesulfonyl chloride and the like can be referred to. The amount of the halogenating agent or the sulfonic ester-forming agent may be appropriately selected from a range of from an equimolar amount to an excessive molar amount based on the diamide represented by general formula (VIII).

As the bases which can be used in this reaction, for example, organic bases such as triethylamine, pyridine and the like and inorganic bases such as potassium carbonate and the like can be referred to. The amount of said base may be appropriately selected from a range of from an equimolar amount to an excessive molar amount based on the diamide of general formula (VIII).

As the inert solvent, the same ones as mentioned in the paragraph of Production Process 1 can be used. Apart from them, other inert solvents such as pyridine and the like can also be used for this purpose.

The reaction can be carried out at a temperature ranging from −20° C. to the boiling point region of the used inert solvent. Although the reaction time may vary depending on the scale and temperature of the reaction, the reaction time is in the range of several minutes to 48 hours.

After completion of the reaction, the product is isolated from the reaction system containing the objective compound in the conventional method, and purified by recrystallization, column chromatography, etc. according to the need, whereby the objective compound can be obtained.

The diamides represented by general formula (VIII) can be produced according to Production Process 1.

2-2. General Formula (VII)→General Formula (I-2)

As the base and the inert solvent used in this reaction, for example, the same bases and inert solvents as mentioned in the paragraph of Production Process 2-1 can be used.

The amount of said base may be appropriately selected from a range of from an equimolar amount to an excessive amount based on the compound of general formula (VII).

The reaction can be carried out at a temperature ranging from −20° C. to the boiling point region of the used inert solvent. Although the reaction time may vary depending on the scale and temperature of the reaction, the reaction time is in the range of several minutes to 48 hours.

After completion of the reaction, the product is isolated from the reaction system containing the objective compound in the conventional method, and purified by recrystallization, column chromatography, etc. according to the need, whereby the objective compound can be obtained.

In the case that R 1 represents -A 1 -R 7 in the general formula (I-1), the compound wherein A 1 is —SO— or —SO 2 — can be prepared from the compound wherein A 1 is —S— by the usual method, for example, an oxidation of the compound wherein A 1 is —S— under the oxidizing agent such as m-chloroperbenzoic acid.

Next, typical examples of the fluoroalkyl-substituted aromatic amine derivative represented by general formula (IV) are listed in Tables 1 to 4, and typical examples of the substituted aromatic amide represented by general formula (I) are listed in Tables 5 to 10. This invention is by no means limited thereby.

In the tables, “Me” means methyl group, “Et” means ethyl group, “Pr” means propyl group, and “Ph” means phenyl group.

In Table 8, physical property of some compounds are expressed in the term of “Amorphous”. 1 H-NMR data of these compounds are shown in Table 11.

Next, typical examples of the present invention are presented below. The present invention is by no means limited by these examples.