Method of producing aromatic amide derivative

The present invention relates to a method of producing an aromatic amide derivative.

International Publications WO 2005/73165, WO 2006/137376, and WO 2010/18714 disclose various compounds as amide derivatives having pest control effects, and also disclose that an amide derivative having a perfluoroalkylated phenyl group is useful in the production of said amide derivatives.

Further, International Publications WO 2010/18857 and WO 2014/161850 disclose a method of producing said amide derivatives.

Technical Problem

Although the amide derivatives are synthesized in WO 2010/18857, their yield is 45% and thus an industrially higher yield thereof has been demanded. In WO 2014/161850, the amide derivatives are synthesized in high yield by way of a protective compound, but the number of processes increases and thus an environmentally shorter process has been desired.

In view of the foregoing problems, the present invention aims to provide a method of producing an aromatic amide derivative in high yield with short processes.

Solution to Problem

The present inventors have made intensive studies in order to solve the above problems and have found that aromatic amide derivatives are obtained in high yield with short processes, thereby completing the present invention. Such aromatic amide derivatives are insecticides having a high insecticidal activity.

That is, the present invention includes the following embodiments.

<1> A method of producing an aromatic amide derivative represented by the following Formula (I), which method includes the following process a and process b:

in Formula (I), R 1 represents a halogen atom; a C 1 -C 4 haloalkyl group; or a substituted C 1 -C 4 haloalkyl group (in R 1 , the term “substituted” means substituted by 1 to 8 substituents, which may be the same or different, selected from the group consisting of a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group, a C 1 -C 4 haloalkoxy group, a C 1 -C 4 alkylthio group, a C 1 -C 4 haloalkylthio group, a C 1 -C 4 alkylamino group, a di-C 1 -C 4 alkylamino group, a cyano group, and a nitro group);

each of X 1 and X 2 independently represents a hydrogen atom, a halogen atom, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 2 -C 4 alkenyl group, a C 2 -C 4 haloalkenyl group, a C 2 -C 4 alkynyl group, a C 2 -C 4 haloalkynyl group, a C 1 -C 4 alkoxy group, a C 1 -C 4 haloalkoxy group, a C 1 -C 4 alkylthio group, a C 1 -C 4 haloalkylthio group, a C 1 -C 4 alkylsulfinyl group, a C 1 -C 4 haloalkylsulfinyl group, a C 1 -C 4 alkylsulfonyl group, a C 1 -C 4 haloalkylsulfonyl group, a C 1 -C 4 alkylamino group, a di-C 1 -C 4 alkylamino group, a cyano group, a nitro group, a C 1 -C 4 alkylcarbonyl group, or a C 1 -C 4 haloalkylcarbonyl group;

each of R 2 and R 3 independently represents a hydrogen atom, a halogen atom, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group, a C 1 -C 4 haloalkoxy group, a C 1 -C 4 alkylthio group, a C 1 -C 4 haloalkylthio group, a C 1 -C 4 alkylsulfinyl group, a C 1 -C 4 haloalkylsulfinyl group, a C 1 -C 4 alkylsulfonyl group, a C 1 -C 4 haloalkylsulfonyl group, a C 1 -C 4 alkylamino group, a di-C 1 -C 4 alkylamino group, a cyano group, or a nitro group;

R 4 represents a hydrogen atom; a C 1 -C 4 alkyl group; a substituted C 1 -C 4 alkyl group; a C 1 -C 4 haloalkyl group; a substituted C 1 -C 4 haloalkyl group; a C 1 -C 4 alkylcarbonyl group; a substituted C 1 -C 4 alkylcarbonyl group; a C 1 -C 4 haloalkylcarbonyl group; a substituted C 1 -C 4 haloalkylcarbonyl group; a C 1 -C 4 alkoxycarbonyl group; a substituted C 1 -C 4 alkoxycarbonyl group; a C 1 -C 4 haloalkoxycarbonyl group; a substituted C 1 -C 4 haloalkoxycarbonyl group; a C 1 -C 4 alkylsulfonyl group; a substituted C 1 -C 4 alkylsulfonyl group; a C 1 -C 4 haloalkylsulfonyl group; or a substituted C 1 -C 4 haloalkylsulfonyl group (in R 4 , the term “substituted” means substituted by 1 to 9 substituents, which may be the same or different, selected from the group consisting of a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group, a C 1 -C 4 haloalkoxy group, a C 1 -C 4 alkylthio group, a C 1 -C 4 haloalkylthio group, a C 1 -C 4 alkylsulfonyl group, a C 1 -C 4 haloalkylsulfonyl group, a C 1 -C 4 alkylamino group, a di-C 1 -C 4 alkylamino group, a C 1 -C 4 alkylcarbonyl group, a C 1 -C 4 alkoxycarbonyl group, a di-C 1 -C 4 alkylaminocarbonyl group, a cyano group, and a nitro group); and

Q represents a C 1 -C 4 alkyl group; a substituted C 1 -C 4 alkyl group; a C 1 -C 4 haloalkyl group; a substituted C 1 -C 4 haloalkyl group; a C 1 -C 4 alkylaminocarbonyl group; a C 1 -C 4 haloalkylaminocarbonyl group; a di-C 1 -C 4 alkylaminocarbonyl group; a di-C 1 -C 4 haloalkylaminocarbonyl group; a phenyl group; a substituted phenyl group; a heterocyclic group; or a substituted heterocyclic group (when Q is “a substituted C 1 -C 4 alkyl group” or “a substituted C 1 -C 4 haloalkyl group”, the term “substituted” means substituted by 1 to 9 substituents, which may be the same or different, selected from the group consisting of a halogen atom, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group, a C 1 -C 4 haloalkoxy group, a C 1 -C 4 alkylthio group, a C haloalkylthio group, a C 1 -C 4 alkylamino group, a di-C 1 -C 4 alkylamino group, a cyano group, and a nitro group. Also, when Q is “a substituted phenyl group”, the term “substituted” means substituted by 1 to 5 substituents, which may be the same or different, selected from the group consisting of a halogen atom, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group, a C 1 -C 4 haloalkoxy group, a C alkylthio group, a C 1 -C 4 haloalkylthio group, a C alkylamino group, a di-C 1 -C 4 alkylamino group, a cyano group, and a nitro group. Further, when Q is “a substituted heterocyclic group”, the term “substituted” means substituted by 1 to 4 substituents, which may be the same or different, selected from the group consisting of a halogen atom, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group, a C haloalkoxy group, a C 1 -C 4 alkylthio group, a C 1 -C 4 haloalkylthio group, a C 1 -C 4 alkylamino group, a di-C 1 -C 4 alkylamino group, a cyano group, and a nitro group. Moreover, said heterocyclic group is a pyridyl group, a pyridyl-N-oxide group, a pyrimidyl group, a pyridazyl group, a pyrazyl group, a furyl group, a thienyl group, an oxazolyl group, an isoxazolyl group, an oxadiazolyl group, a thiazolyl group, an isothiazolyl group, an imidazolyl group, a triazolyl group, a pyrrolyl group, a pyrazolyl group, or a tetrazolyl group.); and

wherein the process a includes reacting an aniline derivative represented by the following Formula (II) with a carboxylic acid derivative represented by the following Formula (III), in the presence of a base, to thereby obtain an imide compound represented by the following Formula (IV):

in Formula (II), R 1 , X 1 , and X 2 are the same as R 1 , X 1 , and X 2 in Formula (I),

Formula (III)

in Formula (III), X 3 represents a halogen atom or a C 1- C 4 alkoxy group, and R 2 , R 3 , R 4 , and Q are the same as R 2 , R 3 , R 4 , and Q in Formula (I),

Formula (IV)

in Formula (IV), R 1 , X 1 , X 2 , R 2 , R 3 , R 4 , and Q are the same as R 1 , X 1 , X 2 , R 2 , R 3 , R 4 , and Q in Formula (I), and two of R 1 , X 1 , X 2 , R 2 , R 3 , R 4 , and Q may be the same or different at each occurrence, respectively, and

the process b includes hydrolyzing the imide compound represented by Formula (IV) to thereby obtain the aromatic amide derivative represented by Formula (I).

<2> The method of producing an aromatic amide derivative according to <1>, wherein:

each of X 1 and X 2 in Formulae (I), (II) and (IV) independently represents a hydrogen atom, a halogen atom, a C 1- C 4 alkyl group, a C 1- C 4 haloalkyl group, a C 1- C 4 alkoxy group, a C 1- C 4 haloalkoxy group, a C 1- C 4 alkylthio group, a C 1- C 4 haloalkylthio group, a C 1- C 4 alkylsulfonyl group, or a C 1- C 4 haloalkylsulfonyl group;

each of R 2 and R 3 in Formulae (I), (III) and (IV) independently represents a hydrogen atom, a halogen atom, a C 1 -C 4 alkoxy group, a C 1 -C 4 haloalkoxy group, a C 1 -C 4 alkylthio group, a C 1 -C 4 haloalkylthio group, a C 1 -C 4 alkylsulfonyl group, a C 1 -C 4 haloalkylsulfonyl group, a C 1 -C 4 alkylamino group, a di-C 1 -C 4 alkylamino group, a cyano group, or a nitro group; and

R 4 in Formulae (I), (III) and (IV) represents a hydrogen atom, a C 1 -C 4 alkyl group, a substituted C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a substituted C 1 -C 4 haloalkyl group, a C 1 -C 4 alkylcarbonyl group, a C 1 -C 4 haloalkylcarbonyl group, a C 1 -C 4 alkoxycarbonyl group, a C 1 -C 4 haloalkoxycarbonyl group, a C 1 -C 4 alkylsulfonyl group, or a C 1 -C 4 haloalkylsulfonyl group (in R 4 , the term “substituted” means substituted by 1 to 9 substituents, which may be the same or different, selected from the group consisting of a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group, a C 1 -C 4 haloalkoxy group, a C 1 -C 4 alkylthio group, a C 1 -C 4 haloalkylthio group, a C 1 -C 4 alkylsulfonyl group, a C 1 -C 4 haloalkylsulfonyl group, a C 1 -C 4 alkylamino group, a di-C 1 -C 4 alkylamino group, a C 1 -C 4 alkylcarbonyl group, a C 1 -C 4 alkoxycarbonyl group, a di-C 1 -C 4 alkylaminocarbonyl group, a cyano group, and a nitro group).

<3> The method of producing an aromatic amide derivative according to <1> or <2>, wherein:

R 2 in Formulae (I), (III) and (IV) represents a hydrogen atom, a halogen atom, a C 1 -C 4 alkoxy group, a C 1 -C 4 haloalkoxy group, a C 1 -C 4 alkylthio group, a C 1 -C 4 haloalkylthio group, a C 1 -C 4 alkylsulfonyl group, a C 1 -C 4 haloalkylsulfonyl group, a C 1 -C 4 alkylamino group, a di-C 1 -C 4 alkylamino group, a cyano group, or a nitro group;

R 3 in Formulae (I), (III) and (IV) represents a hydrogen atom, a halogen atom, a C 1 -C 4 alkoxy group, a cyano group, or a nitro group; and

Q in Formulae (I), (III) and (IV) represents a C 1 -C 4 alkylaminocarbonyl group, a C 1 -C 4 haloalkylaminocarbonyl group, a di-C 1 -C 4 alkylaminocarbonyl group, a di-C 1 -C 4 haloalkylaminocarbonyl group, a phenyl group, a substituted phenyl group, a heterocyclic group, or a substituted heterocyclic group (when Q is “a substituted phenyl group”, the term “substituted” means substituted by 1 to 5 substituents, which may be the same or different, selected from the group consisting of a halogen atom, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group, a C 1 -C 4 haloalkoxy group, a C 1 -C 4 alkylthio group, a C 1 -C 4 haloalkylthio group, a C 1 -C 4 alkylamino group, a di-C 1 -C 4 alkylamino group, a cyano group, and a nitro group. Further, when Q is “a substituted heterocyclic group”, the term “substituted” means substituted by 1 to 4 substituents, which may be the same or different, selected from the group consisting of a halogen atom, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group, a C 1 -C 4 haloalkoxy group, a C 1 -C 4 alkylthio group, a C 1 -C 4 haloalkylthio group, a C 1 -C 4 alkylamino group, a di-C 1 -C 4 alkylamino group, a cyano group, and a nitro group.).

<4> The method of producing an aromatic amide derivative according to any one of <1> to <3>, wherein:

R 2 in Formulae (I), (III) and (IV) represents a hydrogen atom, a halogen atom, a C 1 -C 4 alkoxy group, a C 1 -C 4 alkylamino group, a di-C 1 -C 4 alkylamino group, a cyano group, or a nitro group; and

R 4 in Formulae (I), (III) and (IV) represents a hydrogen atom, a C 1 -C 4 alkyl group, or a C 1 -C 4 haloalkyl group.

<5> The method of producing an aromatic amide derivative according to any one of <1> to <4>, wherein:

R 2 in Formulae (I), (III) and (IV) represents a hydrogen atom, a halogen atom, or a C 1 -C 4 alkoxy group;

R 3 in Formulae (I), (III) and (IV) represents a hydrogen atom, a halogen atom, or a cyano group; and

Q in Formulae (I), (III) and (IV) represents a di-C 1 -C 4 alkylaminocarbonyl group, a phenyl group, a substituted phenyl group, a heterocyclic group, or a substituted heterocyclic group (when Q is “a substituted phenyl group”, the term “substituted” means substituted by 1 to 5 substituents, which may be the same or different, selected from the group consisting of a halogen atom, a cyano group, a nitro group, and a C 1 -C 4 haloalkyl group. Further, when Q is “a substituted heterocyclic group”, the term “substituted” means substituted by 1 to 4 substituents, which may be the same or different, selected from the group consisting of a halogen atom, a cyano group, a nitro group, and a C 1 -C 4 haloalkyl group.).

<6> The method of producing an aromatic amide derivative according to any one of <1> to <5>, wherein:

R 2 in Formulae (I), (III) and (IV) represents a hydrogen atom or a halogen atom;

R 4 in Formulae (I), (III) and (IV) represents a hydrogen atom or a C 1 -C 4 alkyl group; and

Q in Formulae (I), (III) and (IV) represents a phenyl group, a substituted phenyl group, a pyridyl group, or a substituted pyridyl group (when Q is “a substituted phenyl group”, the term “substituted” means substituted by 1 to 5 substituents, which may be the same or different, selected from the group consisting of a halogen atom, a cyano group, and a nitro group. Further, when Q is “a substituted pyridyl group”, the term “substituted” means substituted by 1 to 4 substituents, which may be the same or different, selected from the group consisting of a halogen atom, a cyano group, a nitro group, and a C 1 -C 4 haloalkyl group.).

<7> The method of producing an aromatic amide derivative according to any one of <1> to <6>, in which the method further includes the following process c, process d, and process e, wherein:

the process c includes obtaining a carboxylic acid compound represented by the following Formula (V) produced together with the aromatic amide derivative represented by Formula (I) in the process b, and halogenating or esterifying the carboxylic acid compound, to thereby obtain a carboxylic acid derivative reproducing compound represented by the following Formula (IIIa):

in Formula (V), R 2 represents a hydrogen atom, a halogen atom, a C 1 -C 4 alkoxy group, a C 1 -C 4 alkylamino group, a di-C 1 -C 4 alkylamino group, a cyano group, or a nitro group;

R 3 represents a hydrogen atom or a halogen atom;

R 4 represents a hydrogen atom, a C 1 -C 4 alkyl group, or a C 1 -C 4 haloalkyl group; and

Q represents a di-C 1 -C 4 alkylaminocarbonyl group, a phenyl group, a substituted phenyl group, a heterocyclic group, or a substituted heterocyclic group (when Q is “a substituted phenyl group”, the term “substituted” means substituted by 1 to 5 substituents, which may be the same or different, selected from the group consisting of a halogen atom, a cyano group, a nitro group, and a C 1 -C 4 haloalkyl group. Further, when Q is “a substituted heterocyclic group”, the term “substituted” means substituted by 1 to 4 substituents, which may be the same or different, selected from the group consisting of a halogen atom, a cyano group, a nitro group, and a C 1 -C 4 haloalkyl group. Said heterocyclic group is a pyridyl group, a pyridyl-N-oxide group, a pyrimidyl group, a pyridazyl group, a pyrazyl group, a furyl group, a thienyl group, an oxazolyl group, an isoxazolyl group, an oxadiazolyl group, a thiazolyl group, an isothiazolyl group, an imidazolyl group, a triazolyl group, a pyrrolyl group, a pyrazolyl group, or a tetrazolyl group.);

in Formula (IIIa), R 2 , R 3 , R 4 , X 3 and Q are the same as R 2 , R 3 , R 4 , X 3 and Q in Formula (III);

the process d includes allowing the carboxylic acid derivative reproducing compound obtained in the process c and the aniline derivative represented by Formula (II) to react with each other in the presence of a base to obtain the imide compound represented by Formula (IV); and

the process e includes hydrolyzing the imide compound represented by Formula (IV) obtained in the process d to obtain the aromatic amide derivative represented by Formula (I).

<8> The method of producing an aromatic amide derivative according to <7>, wherein:

R 2 in Formula (V) represents a hydrogen atom or a halogen atom;

R 4 represents a hydrogen atom or a C 1 -C 4 alkyl group; and

Q represents a di-C 1 -C 4 alkylaminocarbonyl group, a phenyl group, a substituted phenyl group, a pyridyl group or a substituted pyridyl group (when Q is “a substituted phenyl group”, the term “substituted” means substituted by 1 to 5 substituents, which may be the same or different, selected from the group consisting of a halogen atom, a cyano group, and a nitro group. Further, when Q is “a substituted pyridyl group”, the term “substituted” means substituted by 1 to 4 substituents, which may be the same or different, selected from the group consisting of a halogen atom and a C 1 -C 4 haloalkyl group.).

Advantageous Effects of Invention

According to the present invention, a method of producing an aromatic amide derivative in high yield with a short process can be provided.

In this specification, the term “process” includes not only an independent process, but also a case in which the process cannot be clearly distinguished from another process, as long as the predetermined action of the process is achieved.

Further, a numerical range expressed using “to” denotes a range including numerical values described in front of and behind “to”, as the minimum value and the maximum value, respectively.

The terms used in Formulae described in this specification have the definitions as described below, respectively, on the basis of their definitions.

“Halogen atom” represents a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom.

The term “n-” means “normal”, “i-” means “iso”, “s-” means “secondary”, and “t-” means “tertiary”.

Concerning the expression “C a -C b (wherein each of a and b represents an integer of 1 or more)”, for example, “C 1 -C 3 ” means that the number of carbon atoms is from 1 to 3, “C 2 -C 6 ” means that the number of carbon atoms is from 2 to 6, and “C 1 -C 4 ” means that the number of carbon atoms is from 1 to 4.

Further, in the following explanations on the substituents with a limitation of the number of carbon atoms, “C a -C b XX group (wherein “XX group” represents name of a substituent group and each of a and b represents an integer of 1 or more)” means, for example, in a case of “C 1 -C 3 XX group”, to represent a XX group having 1 to 3 carbon atoms and also include the range covered by the substituent having each number of carbon atoms, such as a XX group having 1 carbon atom, a XX group having 2 carbon atoms and a XX group having 3 carbon atoms, as a subordinate concept. In addition, “C a -C b XX group” also includes the range covered by the substituent in which the upper limit and the lower limit of the number of carbon atoms are optionally combined within the acceptable range, for example, in a case of “C 1 -C 3 XX group”, such as “C 1 -C 2 XX group” and “C 2 -C 3 XX group” are also included.

“C 1 -C 3 Alkyl group” represents a linear or branched alkyl group having from 1 to 3 carbon atoms, for example, a methyl group, an ethyl group, an n-propyl group, an i-propyl group, or the like, and “C 1 -C 4 alkyl group” represents a linear or branched alkyl group having from 1 to 4 carbon atoms, for example, an n-butyl group, an s-butyl group, i-butyl, a t-butyl group, or the like, in addition to the “C 1 -C 3 alkyl group”.

“C 1 -C 4 haloalkyl group” represents a linear or branched alkyl group having from 1 to 4 carbon atoms and being substituted with one or more halogen atoms which may be the same or different, for example, a monofluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a monochloromethyl group, a dichloromethyl group, a trichloromethyl group, a monobromomethyl group, a dibromomethyl group, a tribromomethyl group, a 1-fluoroethyl group, a 2-fluoroethyl group, a 2,2-difluoroethyl group, a 2,2,2-trifluoroethyl group, a 1-chloroethyl group, a 2-chloroethyl group, a 2,2-dichloroethyl group, a 2,2,2-trichloroethyl group, a 1-bromoethyl group, a 2-bromoethyl group, a 2,2-dibromoethyl group, a 2,2,2-tribromoethyl group, a 2-iodoethyl group, a pentafluoroethyl group, a 3-fluoro-n-propyl group, a 3-chloro-n-propyl group, a 3-bromo-n-propyl group, a 1,3-difluoro-2-propyl group, a 1,3-dichloro-2-propyl group, a 1,1,1-trifluoro-2-propyl group, a 1-chloro-3-fluoro-2-propyl group, a 1,1,1,3,3,3-hexafluoro-2-propyl group, a 1,1,1,3,3,3-hexafluoro-2-chloro-2-propyl group, a 2,2,3,3,3-pentafluoro-n-propyl group, a heptafluoro-i-propyl group, a heptafluoro-n-propyl group, a 4-fluoro-n-butyl group, a nonafluoro-n-butyl group, a nonafluoro-2-butyl group, a nonafluoro-i-butyl group, or the like.

“C 2 -C 4 alkenyl group” represents an alkenyl group having from 2 to 4 carbon atoms and a double bond in the carbon chain, for example, a vinyl group, an allyl group, a 2-butenyl group, a 3-butenyl group, or the like.

“C 2 -C 4 haloalkenyl group” represents a linear or branched alkenyl group having from 2 to 4 carbon atoms and a double bond in the carbon chain, and being substituted with one or more halogen atoms which may be the same or different, for example, a 3,3-difluoro-2-propenyl group, a 3,3-dichloro-2-propenyl group, a 3,3-dibromo-2-propenyl group, a 2,3-dibromo-2-propenyl group, a 4,4-difluoro-3-butenyl group, a 3,4,4-tribromo-3-butenyl group, or the like.

“C 2 -C 4 alkynyl group” represents a linear or branched alkynyl group having from 2 to 4 carbon atoms and a triple bond in the carbon chain, for example, a propargyl group, a 1-butyn-3-yl group, a 1-butyn-3-methyl-3-yl group, or the like.

“C 2 -C 4 haloalkynyl group” represents a linear or branched alkynyl group having from 2 to 4 carbon atoms and a triple bond in the carbon chain, and being substituted with one or more halogen atoms which may be the same or different, for example, a 3,3-difluoropropyne-1-yl group, a 3,3,3-trifluoropropyne-1-yl group, a 4,4,4-trifluoro-3,3-difluoro-butyne-1-yl group, or the like.

“C 1 -C 4 alkoxy group” represents a linear or branched alkoxy group having from 1 to 4 carbon atoms, for example, a methoxy group, an ethoxy group, an n-propyloxy group, an isopropyloxy group, an n-butyloxy group, an i-butyloxy group, or the like.

“C 1 -C 4 haloalkoxy group” represents a linear or branched haloalkoxy group having from 1 to 4 carbon atoms and being substituted with one or more halogen atoms which may be the same or different, for example, a trifluoromethoxy group, a 1,1,1,3,3,3-hexafluoro-2-propyloxy group, a 2,2,2-trifluoroethoxy group, a 2-chloroethoxy group, a 3-fluoro-n-propyloxy group, a 1,1,1,3,3,4,4,4-octafluoro-2-butyloxy group, or the like.

“C 1 -C 4 alkylthio group” represents a linear, branched, or cyclic alkylthio group having from 1 to 4 carbon atoms, for example, a methylthio group, an ethylthio group, an n-propylthio group, an i-propylthio group, a cyclopropylthio group, an n-butylthio group, an i-butylthio group, an s-butylthio group, a t-butylthio group, a cyclopropylmethylthio group, or the like.

“C 1 -C 4 haloalkylthio group” represents a linear or branched alkylthio group having from 1 to 4 carbon atoms and being substituted with one or more halogen atoms which may be the same or different, for example, a trifluoromethylthio group, a pentafluoroethylthio group, a 2,2,2-trifluoroethylthio group, a heptafluoro-n-propylthio group, a heptafluoro-i-propylthio group, a nonafluoro-n-butylthio group, a nonafluoro-i-butylthio group, a nonafluoro-s-butylthio group, a 4,4,4-trifluoro-n-butylthio group, or the like.

“C 1 -C 4 alkylsulfinyl group” represents a linear, branched, or cyclic alkylsulfinyl group having from 1 to 4 carbon atoms, for example, a methylsulfinyl group, an ethylsulfinyl group, an n-propylsulfinyl group, an i-propylsulfinyl group, a cyclopropylsulfinyl group, an n-butylsulfinyl group, an i-butylsulfinyl group, or the like.

“C 1 -C 4 haloalkylsulfinyl group” represents a linear or branched alkylsulfinyl group having from 1 to 4 carbon atoms and being substituted with one or more halogen atoms which may be the same or different, for example, a trifluoromethylsulfinyl group, a pentafluoroethylsulfinyl group, a 2,2,2-trifluoroethylsulfinyl group, a heptafluoro-n-propylsulfinyl group, a heptafluoro-i-propylsulfinyl group, a nonafluoro-n-butylsulfinyl group, a nonafluoro-i-butylsulfinyl group, a nonafluoro-s-butylsulfinyl group, a 4,4,4-trifluoro-n-butylsulfinyl group, or the like.

“C 1 -C 4 alkylsulfonyl group” represents a linear, branched, or cyclic alkylsulfonyl group having from 1 to 4 carbon atoms, for example, a methylsulfonyl group, an ethylsulfonyl group, an n-propylsulfonyl group, an i-propylsulfonyl group, a cyclopropylsulfonyl group, an n-butylsulfonyl group, an i-butylsulfonyl group, or the like.

“C 1 -C 4 haloalkylsulfonyl group” represents a linear or branched alkylsulfonyl group having from 1 to 4 carbon atoms and being substituted with one or more halogen atoms which may be the same or different, for example, a trifluoromethylsulfonyl group, a pentafluoroethylsulfonyl group, a 2,2,2-trifluoroethylsulfonyl group, a heptafluoro-n-propyl sulfonyl group, a heptafluoro-i-propyl sulfonyl group, a nonafluoro-n-butyl sulfonyl group, a nonafluoro-s-butyl sulfonyl group, or the like. “C 1 -C 4 alkylamino group” represents a linear, branched, or cyclic alkylamino group having from 1 to 4 carbon atoms, for example, a methylamino group, an ethylamino group, an n-propylamino group, an i-propylamino group, an n-butylamino group, a cyclopropylamino group, or the like.

“Di-C 1 -C 4 -alkylamino group” represents an amino group substituted with two linear or branched alkyl groups each having from 1 to 4 carbon atoms, which may be the same or different, for example, a dimethylamino group, a diethylamino group, an N-ethyl-N-methylamino group, or the like.

“C 1 -C 4 alkylcarbonyl group” represents a linear, branched, or cyclic alkylcarbonyl group having from 1 to 4 carbon atoms, for example, a formyl group, an acetyl group, a propionyl group, an isopropylcarbonyl group, a cyclopropylcarbonyl group, or the like. “C 1 -C 4 haloalkylcarbonyl group” represents a linear or branched alkylcarbonyl group having from 1 to 4 carbon atoms and being substituted with one or more halogen atoms which may be the same or different, for example, a fluoroacetyl group, a difluoroacetyl group, a trifluoroacetyl group, a chloroacetyl group, a dichloroacetyl group, a trichloroacetyl group, a bromoacetyl group, an iodoacetyl group, a 3,3,3-trifluoropropionyl group, a 2,2,3,3,3-pentafluoropropionyl group, or the like.

“C 1 -C 4 alkylcarbonyloxy group” represents a linear or branched alkylcarbonyloxy group having from 1 to 4 carbon atoms, for example, an acetoxy group, a propionyloxy group, or the like.

“C 1 -C 4 alkoxycarbonyl group” represents a linear or branched alkoxycarbonyl group having from 1 to 4 carbon atoms, for example, a methoxycarbonyl group, an ethoxycarbonyl group, an isopropyloxycarbonyl group, or the like.

“C 1 -C 4 perfluoroalkyl group” represents a linear or branched alkyl group having from 1 to 4 carbon atoms and being completely substituted with fluorine atoms, for example, a trifluoromethyl group, a pentafluoroethyl group, a heptafluoro-n-propyl group, a heptafluoro-i-propyl group, a nonafluoro-n-butyl group, a nonafluoro-2-butyl group, a nonafluoro-i-butyl group, or the like.

“C 1 -C 4 perfluoroalkylthio group” represents a linear or branched alkylthio group having from 1 to 4 carbon atoms and being completely substituted with fluorine atoms, for example, a trifluoromethylthio group, a pentafluoroethylthio group, a heptafluoro-n-propylthio group, a heptafluoro-i-propylthio group, a nonafluoro-n-butylthio group, a nonafluoro-2-butylthio group, a nonafluoro-i-butylthio group, or the like.

“C 1 -C 4 perfluoroalkylsulfinyl group” represents a linear or branched alkylsulfinyl group having from 1 to 4 carbon atoms and being completely substituted with fluorine atoms, for example, a trifluoromethylsulfinyl group, a pentafluoroethylsulfinyl group, a heptafluoro-n-propylsulfinyl group, a heptafluoro-i-propylsulfinyl group, a nonafluoro-n-butylsulfinyl group, a nonafluoro-2-butylsulfinyl group, a nonafluoro-i-butylsulfinyl group, or the like.

“C 1 -C 4 perfluoroalkylsulfonyl group” represents a linear or branched alkylsulfonyl group having from 1 to 4 carbon atoms and being completely substituted with fluorine atoms, for example, a trifluoromethylsulfonyl group, a pentafluoroethylsulfonyl group, a heptafluoro-n-propyl sulfonyl group, a heptafluoro-i-propyl sulfonyl group, a nonafluoro-n-butyl sulfonyl group, a nonafluoro-2-butyl sulfonyl group, a nonafluoro-i-butyl sulfonyl group, or the like.

In the invention, the compounds represented by Formula (I), Formula (II), Formula (III), Formula (IIIa), Formula (IV), Formula (V), or the like may include one or two or more chiral carbon atoms or chiral centers in their structural Formulae, and thus may have two or more optical isomers. The scope of the invention encompasses all of the individual optical isomers and any mixture containing such optical isomers in any proportion.

Further, the compound represented by Formula (I), Formula (II), Formula (III), Formula (IIIa), Formula (IV), Formula (V), or the like in the invention may have two or more geometrical isomers originating from carbon-carbon double bond(s) in their structural Formulae. The scope of the invention also encompasses any mixture containing such geometrical isomers in any proportion.

The method of producing an aromatic amide derivative represented by the following Formula (I) of the invention (hereinafter, simply referred to as “production method of the invention”) includes a process (process a) of obtaining an imide compound represented by Formula (IV) by reacting an aniline derivative represented by Formula (II) with a carboxylic acid derivative represented by Formula (III) in the presence of a base and a process (process b) of obtaining the aromatic amide derivative represented by Formula (I) by hydrolyzing the imide compound represented by Formula (IV).

In addition, the production method of the invention may further include, if necessary, a process (process c) of obtaining the carboxylic acid derivative reproducing compound represented by Formula (IIIa) by isolating and purifying the carboxylic acid compound represented by Formula (V) obtained together with the aromatic amide derivative represented by Formula (I) in the hydrolysis of the imide compound represented by Formula (IV) in the process b, and by halogenating or esterifying the carboxylic acid compound; a process (process d) of obtaining the imide compound represented by Formula (IV) by reacting the carboxylic acid derivative reproducing compound represented by Formula (IIIa) obtained in the process c with the aniline derivative represented by Formula (II) in the presence of a base; and a process (process e) of obtaining the aromatic amide derivative represented by Formula (I) by hydrolyzing the imide compound represented by Formula (IV) obtained in the process d.

The imide compound represented by Formula (IV) in the invention is a useful intermediate particularly in producing the compound represented by Formula (I), which is useful as an insecticide.

In Formula (IV), R 1 represents a halogen atom; a C 1 -C 4 haloalkyl group; or a C 1 -C 4 haloalkyl group substituted by 1 to 8 substituents, which may be the same or different, selected from the group consisting of a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group, a C 1 -C 4 haloalkoxy group, a C 1 -C 4 alkylthio group, a C 1 -C 4 haloalkylthio group, a C 1 -C 4 alkylamino group, a di-C 1 -C 4 alkylamino group, a cyano group, and a nitro group, and R 1 is preferably a C 1 -C 4 haloalkyl group.

In Formula (IV), each of X 1 and X 2 independently represents a hydrogen atom, a halogen atom, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 2 -C 4 alkenyl group, a C 2 -C 4 haloalkenyl group, a C 2 -C 4 alkynyl group, a C 2 -C 4 haloalkynyl group, a C 1 -C 4 alkoxy group, a C 1 -C 4 haloalkoxy group, a C 1 -C 4 alkylthio group, a C 1 -C 4 haloalkylthio group, a C 1 -C 4 alkylsulfinyl group, a C 1 -C 4 haloalkylsulfinyl group, a C 1 -C 4 alkylsulfonyl group, a C 1 -C 4 haloalkylsulfonyl group, a C 1 -C 4 alkylamino group, a di-C 1 -C 4 alkylamino group, a cyano group, a nitro group, a C 1 -C 4 alkylcarbonyl group, or a C 1 -C 4 haloalkylcarbonyl group; represents preferably a hydrogen atom, a halogen atom, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group, a C 1 -C 4 haloalkoxy group, a C 1 -C 4 alkylthio group, a C 1 -C 4 haloalkylthio group, a C 1 -C 4 alkylsulfonyl group, or a C 1 -C 4 haloalkylsulfonyl group; and represents more preferably a halogen atom, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, or a C 1 -C 4 haloalkylsulfonyl group.

In Formula (IV), each of R 2 and R 3 independently represents a hydrogen atom, a halogen atom, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group, a C 1 -C 4 haloalkoxy group, a C 1 -C 4 alkylthio group, a C 1 -C 4 haloalkylthio group, a C 1 -C 4 alkylsulfinyl group, a C 1 -C 4 haloalkylsulfinyl group, a C 1 -C 4 alkylsulfonyl group, a C 1 -C 4 haloalkylsulfonyl group, a C 1 -C 4 alkylamino group, a di-C 1 -C 4 alkylamino group, a cyano group, or a nitro group, and are preferably a hydrogen atom, a halogen atom, a C 1 -C 4 alkoxy group, a C 1 -C 4 haloalkoxy group, a C 1 -C 4 alkylthio group, a C 1 -C 4 haloalkylthio group, a C 1 -C 4 alkylsulfonyl group, a C 1 -C 4 haloalkylsulfonyl group, a C 1 -C 4 alkylamino group, a di-C 1 -C 4 alkylamino group, a cyano group, or a nitro group.

R 2 represents more preferably a hydrogen atom, a halogen atom, a C 1 -C 4 alkoxy group, a C 1 -C 4 haloalkoxy group, a C 1 -C 4 alkylthio group, a C 1 -C 4 haloalkylthio group, a C 1 -C 4 alkylsulfonyl group, a C 1 -C 4 haloalkylsulfonyl group, a C 1 -C 4 alkylamino group, a di-C 1 -C 4 alkylamino group, a cyano group, or a nitro group; even more preferably a hydrogen atom, a halogen atom, a C 1 -C 4 alkoxy group, a C 1 -C 4 alkylamino group, a di-C 1 -C 4 alkylamino group, a cyano group, or a nitro group; especially preferably a hydrogen atom, a halogen atom, or a C 1 -C 4 alkoxy group. R 3 represents more preferably a hydrogen atom, a halogen atom, a C 1 -C 4 alkoxy group, a cyano group, or a nitro group; even more preferably a hydrogen atom, a halogen atom, a nitro group or a cyano group; and especially preferably a hydrogen atom, a halogen atom, or a cyano group.

Two of R 2 may be the same or different at each occurrence, and two of R 3 may be the same or different at each occurrence.

In Formula (IV), R 4 represents a hydrogen atom; a C 1 -C 4 alkyl group; a C 1 -C 4 haloalkyl group; a C 1 -C 4 alkylcarbonyl group; a C 1 -C 4 haloalkylcarbonyl group; a C 1 -C 4 alkoxycarbonyl group; a C 1 -C 4 haloalkoxycarbonyl group; a C 1 -C 4 alkylsulfonyl group; a C 1 -C 4 haloalkylsulfonyl group; or a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkylcarbonyl group, a C 1 -C 4 haloalkylcarbonyl group, a C 1 -C 4 alkoxycarbonyl group, a C 1 -C 4 haloalkoxycarbonyl group, a C 1 -C 4 alkylsulfonyl group, or a C 1 -C 4 haloalkylsulfonyl group, substituted by 1 to 9 substituents, which may be the same or different, selected from the group consisting of a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group, a C 1 -C 4 haloalkoxy group, a C 1 -C 4 alkylthio group, a C 1 -C 4 haloalkylthio group, a C 1 -C 4 alkylsulfonyl group, a C 1 -C 4 haloalkylsulfonyl group, a C 1 -C 4 alkylamino group, a di-C 1 -C 4 alkylamino group, a C 1 -C 4 alkylcarbonyl group, a C 1 -C 4 alkoxycarbonyl group, a di-C 1 -C 4 alkylaminocarbonyl group, a cyano group, and a nitro group.

Two of R 4 may be the same or different at each occurrence.

R 4 may form a C 1 -C 6 heterocyclic ring when taken together with Q.

R 4 represents preferably a hydrogen atom, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkylcarbonyl group, a a C 1 -C 4 alkoxycarbonyl group, or a C 1 -C 4 alkylsulfonyl group; more preferably a hydrogen atom, a C 1 -C 4 alkyl group, or a C 1 -C 4 haloalkyl group; and even more preferably a hydrogen atom or a C 1 -C 4 alkyl group.

In Formula (IV), Q represents a C 1 -C 4 alkyl group; a C 1 -C 4 haloalkyl group; a C 1 -C 4 alkylaminocarbonyl group; a C 1 -C 4 haloalkylaminocarbonyl group; a di-C 1 -C 4 alkylaminocarbonyl group; a di-C 1 -C 4 haloalkylaminocarbonyl group; a phenyl group; a heterocyclic group; a C 1 -C 4 alkyl group or a C 1 -C 4 haloalkyl group, substituted by 1 to 9 substituents, which may be the same or different, selected from the group consisting of a halogen atom, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group, a C 1 -C 4 haloalkoxy group, a C 1 -C 4 alkylthio group, a C 1 -C 4 haloalkylthio group, a C 1 -C 4 alkylamino group, a di-C 1 -C 4 alkylamino group, a cyano group, and a nitro group; a phenyl group substituted by 1 to 5 substituents, which may be the same or different, selected from the group consisting of a halogen atom, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group, a C 1 -C 4 haloalkoxy group, a C 1 -C 4 alkylthio group, a C 1 -C 4 haloalkylthio group, a C 1 -C 4 alkylamino group, a di-C 1 -C 4 alkylamino group, a cyano group, and a nitro group; or a heterocyclic group substituted by 1 to 4 substituents, which may be the same or different, selected from the group consisting of a halogen atom, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group, a C 1 -C 4 haloalkoxy group, a C 1 -C 4 alkylthio group, a C 1 -C 4 haloalkylthio group, a C 1 -C 4 alkylamino group, a di-C 1 -C 4 alkylamino group, a cyano group, and a nitro group; wherein the heterocyclic group is a pyridyl group, a pyridyl-N-oxide group, a pyrimidyl group, a pyridazyl group, a pyrazyl group, a furyl group, a thienyl group, an oxazolyl group, an isoxazolyl group, an oxadiazolyl group, a thiazolyl group, an isothiazolyl group, an imidazolyl group, a triazolyl group, a pyrrolyl group, a pyrazolyl group, or a tetrazolyl group.

Two of Q may be the same or different at each occurrence.

Q represents preferably a C 1 -C 4 alkylaminocarbonyl group; a C 1 -C 4 haloalkylaminocarbonyl group; a di-C 1 -C 4 alkylaminocarbonyl group; a di-C 1 -C 4 haloalkylaminocarbonyl group; a phenyl group; a heterocyclic group; a phenyl group substituted by 1 to 5 substituents, which may be the same or different, selected from the group consisting of a halogen atom, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group, a C 1 -C 4 haloalkoxy group, a C 1 -C 4 alkylthio group, a C 1 -C 4 haloalkylthio group, a C 1 -C 4 alkylamino group, a di-C 1 -C 4 alkylamino group, a cyano group, and a nitro group; or a heterocyclic group substituted by 1 to 4 substituents, which may be the same or different, selected from the group consisting of a halogen atom, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group, a C 1 -C 4 haloalkoxy group, a C 1 -C 4 alkylthio group, a C 1 -C 4 haloalkylthio group, a C 1 -C 4 alkylamino group, a di-C 1 -C 4 alkylamino group, a cyano group, and a nitro group; more preferably a phenyl group; a heterocyclic group; a phenyl group substituted by 1 to 5 substituents, which may be the same or different, selected from the group consisting of a halogen atom, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group, a C 1 -C 4 haloalkoxy group, a C 1 -C 4 alkylthio group, a C 1 -C 4 haloalkylthio group, a C 1 -C 4 alkylamino group, a di-C 1 -C 4 alkylamino group, a cyano group, and a nitro group; or a heterocyclic group substituted by 1 to 4 substituents, which may be the same or different, selected from the group consisting of a halogen atom, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, a C 1 -C 4 alkoxy group, a C 1 -C 4 haloalkoxy group, a C 1 -C 4 alkylthio group, a C 1 -C 4 haloalkylthio group, a C 1 -C 4 alkylamino group, a di-C 1 -C 4 alkylamino group, a cyano group, and a nitro group; even more preferably a di-C 1 -C 4 alkylaminocarbonyl group; a phenyl group; a heterocyclic group; a phenyl group substituted by 1 to 5 substituents, which may be the same or different, selected from the group consisting of a halogen atom, a cyano group, a nitro group, and a C 1 -C 4 haloalkyl group; or a heterocyclic group substituted by 1 to 4 substituents, which may be the same or different, selected from the group consisting of a halogen atom, a cyano group, a nitro group, and a C 1 -C 4 haloalkyl group; particularly preferably a phenyl group; a pyridyl group; a phenyl group substituted by 1 to 5 substituents, which may be the same or different, selected from the group consisting of a halogen atom, a cyano group, and a nitro group; or a pyridyl group substituted by 1 to 4 substituents, which may be the same or different, selected from the group consisting of a halogen atom, a cyano group, a nitro group, and a C 1 -C 4 haloalkyl group.

R 1 , X 1 , X 2 , R 2 , R 3 , R 4 , and Q in Formula (I) have the same meanings as R 1 , X 1 , X 2 , R 2 , R 3 , R 4 , and Q in Formula (IV), respectively. The same shall be applied to preferred embodiments.

R 1 , X 1 , and X 2 in Formula (II) have the same meanings as R 1 , X 1 , and X 2 in Formula (IV), respectively. The same shall be applied to preferred embodiments.

X 3 in Formula (III) represents a halogen atom or a C 1 -C 4 alkoxy group, and R 2 , R 3 , R 4 , and Q have the same meanings as R 2 , R 3 , R 4 , and Q in Formula (IV). The same shall be applied to preferred embodiments.

R 2 , R 3 , R 4 , and Q in Formula (V) have the same meanings as R 2 , R 3 , R 4 , and Q in Formula (IV), and the same shall be applied to preferred embodiments.

In the chemical structure represented by a Formula, the range of the limitations on each of and every substituent described above are combinable in any arbitrary level, and the entire range of the limitations of the chemical structures represented by the Formula resulted from the arbitrary combinations are explicitly disclosed herein, as if each and every combination was indivisually and explicitly recited.

The production method of the invention will be described as follows.

First, the process a will be described.

The process a is, as shown in the following reaction scheme, a process of obtaining an imide compound represented by Formula (IV) by reacting an aniline derivative represented by Formula (II) with a carboxylic acid derivative represented by Formula (III) in the presence of a base.

Examples of the bases to be used in the above reaction may include organic bases such as triethylamine, tri-n-butylamine, pyridine, 4-dimethylaminopyridine, 1,4-diazabicyclo[2.2.2]octane, diazabicycloundecene, and diazabicyclononene; alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; carbonates such as sodium hydrogen carbonate and potassium carbonate; phosphates such as dipotassium monohydrogen phosphate and trisodium phosphate; alkali metal hydrides such as sodium hydride; alkali metal alcoholates such as sodium methoxide and sodium ethoxide; and the like. These bases may be used alone or as a mixture of two or more thereof.

Among these, the organic bases such as triethylamine, tri-n-butylamine, and 4-dimethylaminopyridine can be particularly preferably used in the above reaction.

Such base may be used in an amount appropriately selected within the range of from 0.01-fold molar equivalents to 10-fold molar equivalents, and preferably within the range of from 2-fold molar equivalents to 4-fold molar equivalents, with respect to the aniline derivative represented by Formula (II). The base may be used in an amount appropriately selected within the above range.

The above reaction may be carried out in the absence of a solvent or may be carried out in the presence of an inert solvent.

The inert solvent is not particularly limited as long as the solvent does not significantly inhibit the progress of the reaction. Examples of the inert solvent may include aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as dichloromethane, chloroform, and carbon tetrachloride; chained or cyclic ethers such as diethyl ether, dioxane, tetrahydrofuran, and 1,2-dimethoxyethane; esters such as ethyl acetate and butyl acetate; alcohols such as methanol and ethanol; ketones such as acetone, methyl isobutyl ketone, and cyclohexanone; amides such as N,N-dimethylformamide, N,N-dimethyl acetamide, 1,3-dimethyl-2-imidazolidinon, and N-methyl-2-pyrrolidone; nitriles such as acetonitrile; and dimethylsulfoxide. These solvents may be used alone or as a mixture of two or more kinds thereof.

Among them, at least one member as an inert solvent selected from the group consisting of benzene, toluene, and xylene can be particularly preferably used.

Concerning the amount of the inert solvent used, such inert solvent may be used in an amount appropriately selected within the range of from 2-fold by mass to 20-fold by mass, and preferably within the range of from 2-fold by mass to 10-fold by mass, with respect to the amount of the aniline derivative represented by Formula (II) used. The inert solvent may be used in an amount appropriately selected within the above range.

The reaction temperature in the above reaction may be appropriately selected within the range of from −20° C. to 200° C., preferably within the range of from 50° C. to 120° C., and in the case of using an inert solvent, the reaction temperature may be any temperature that is lower than or equal to the boiling point. The reaction time may be appropriately selected within the range of from several minutes to 96 hours and preferably within the range of from several minutes to 24 hours.

The amount of the carboxylic acid derivative represented by Formula (III) used in the above reaction is not particularly limited, with respect to the amount of the aniline derivative represented by Formula (II) used. For example, from the viewpoint of economy, the carboxylic acid derivative represented by Formula (III) is used preferably in an amount of from 2-fold molar equivalents to 5-fold molar equivalents, more preferably in an amount of from 2-fold molar equivalents to 3-fold molar equivalents, with respect to the amount of the aniline derivative represented by Formula (II) used.

In the process a as described above, the imide compound represented by Formula (IV), which is the aimed product, may be isolated from the reaction system after the completion of the reaction, according to a conventional method, and, if necessary, purification may be carried out by an operation such as recrystallization, column chromatography, or distillation.

The above explained reaction conditions in the process a, such as type and amount of the base, and the inert solvent, reaction temperature, reaction time, or the like are combinable in any arbitrary level, and each and every such combination is explicitly disclosed herein, as if each and every aspect was individually and explicitly recited.

The aniline derivative represented by Formula (II) can be synthesized by the method described in EP 2,319,830. Further, the carboxylic acid derivative represented by Formula (III) can be synthesized by the method described in WO 2010/018857 A1.

Next, the process b will be described.

The process b is, as shown in the following reaction scheme, a process of obtaining the aromatic amide derivative represented by Formula (I) by hydrolyzing the imide compound represented by (IV). In the process b, the carboxylic acid compound represented by Formula (V) can be obtained together with the aromatic amide derivative represented by Formula (I).

The hydrolysis in the above reaction indicates that the imide compound represented by Formula (IV) is decomposed to the aromatic amide derivative represented by Formula (I) and the carboxylic acid compound represented by Formula (V) with an acid or a base in the presence of water.

The acid used in the hydrolysis includes hydrogen chloride, hydrogen bromide, hydrogen iodide, sulfuric acid, and nitric acid, and hydrogen chloride and sulfuric acid are preferable.

The base used in the hydrolysis includes alkali metal hydroxides such as lithium hydroxide, sodium hydroxide, and potassium hydroxide; carbonates such as sodium hydrogen carbonate, sodium carbonate, and potassium carbonate; alkali metal alcoholates such as sodium methoxide and sodium ethoxide; organic bases such as triethylamine, 4-dimethylaminopyridine and pyridine; and the like. Among these, as the base, at least one member selected from the group consisting of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, and 4-dimethylaminopyridine can be particularly preferably used.

The amount of the acid or base used is, for example, in the range of from 0.5-fold molar equivalents to 20-fold molar equivalents, preferably from 0.5-fold molar equivalents to 10-fold molar equivalents, with respect to the amount of the imide compound represented by Formula (IV) used. Such acids or bases may be used in an amount appropriately selected within the above range.

The above reaction may be carried out in the absence of a solvent or may be carried out in the presence of an inert solvent.

The inert solvent is not particularly limited as long as the solvent does not significantly inhibit the progress of the reaction. Examples of the inert solvent may include aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as dichloromethane, chloroform, and carbon tetrachloride; chained or cyclic ethers such as diethyl ether, dioxane, tetrahydrofuran, and 1,2-dimethoxyethane; esters such as ethyl acetate and butyl acetate; alcohols such as methanol and ethanol; ketones such as acetone, methyl isobutyl ketone, and cyclohexanone; amides such as N,N-dimethylformamide, N,N-dimethylacetamide, 1,3-dimethyl-2-imidazolidinon, and N-methyl-2-pyrrolidone; nitriles such as acetonitrile; and dimethylsulfoxide. These solvents may be used alone or as a mixture of two or more kinds thereof.

Among them, at least one member as an inert solvent selected from the group consisting of tetrahydrofuran, methanol, 1,3-dimethyl-2-imidazolidinon, toluene, and xylene can be particularly preferably used.

Concerning the amount of the inert solvent used, such a solvent may be used, for example, in an amount appropriately selected within the range of from 1-fold by mass to 15-fold by mass, and preferably within the range of from 1-fold by mass to 10-fold by mass, with respect to the mount of the imide compound represented by Formula (IV) used. The inert solvent may be used in an amount appropriately selected within the above range.

The reaction temperature in the above reaction may be appropriately selected within the range of from −20° C. to 200° C., preferably within the range of from 50° C. to 120° C., and in the case of using an inert solvent, the reaction temperature may be any temperature that is lower than or equal to the boiling point. The reaction time may be appropriately selected within the range of from several minutes to 96 hours, and preferably within the range of from several minutes to 24 hours.

In the process b as described above, the aromatic amide derivative represented by Formula (I), which is the aimed product, may be isolated from the reaction system after the completion of the reaction, according to a conventional method, and, if necessary, purification may be carried out by an operation such as recrystallization, column chromatography, or distillation.

The above explained reaction conditions in the process b, such as type and amount of the acid, the base, and the inert solvent, reaction temperature, reaction time, or the like are combinable in any arbitrary level, and each and every such combination is explicitly disclosed herein, as if each and every aspect was individually and explicitly recited.

In the case of using an acid for hydrolysis in the process b, the carboxylic acid compound represented by Formula (V), which is obtained together with the aromatic amide derivative represented by Formula (I), may be isolated by filtration after the completion of the reaction. In the case of using a base for hydrolysis in the process b, the carboxylic acid compound represented by Formula (V) may be obtained by subjecting the aqueous phase to acid precipitation, followed by filtration. The isolated carboxylic acid compound may be optionally purified by an operation such as recrystallization and column chromatography.

Then, the process c will be described.

The process c is, as shown in the following reaction scheme, a process of obtaining the carboxylic acid derivative reproducing compound represented by Formula (IIIa) by halogenating or esterifying the carboxylic acid compound represented by Formula (V), which is obtained together with the aromatic amide derivative represented by Formula (I) in the hydrolysis of the imide compound represented by Formula (IV).

The halogenation in the above reaction is a reaction of obtaining the carboxylic acid derivative reproducing compound represented by Formula (IIIa) from the carboxylic acid compound represented by Formula (V) using a halogenating agent, and the esterification is a reaction of obtaining the carboxylic acid derivative reproducing compound represented by Formula (IIIa) from the carboxylic acid compound represented by Formula (V) using an acid catalyst in the presence of an alcohol.

The halogenating agent used in the above halogenation reaction includes phosgene, triphosgene, thionyl chloride, oxalyl chloride, phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride, phosphorus tribromide, and the like, and thionyl chloride, oxalyl chloride, and phosphorus oxychloride are preferable.

The amount of the halogenating agent used is, for example, in the range of from 0.2-fold molar equivalents to 10-fold molar equivalents, preferably in the range of from 0.5-fold molar equivalents to 2-fold molar equivalents, with respect to the amount of the carboxylic acid compound represented by Formula (V) used. The halogenating agent may be used in an amount appropriately selected within the above range.

Examples of the acid catalyst used for the esterification reaction are sulfuric acid, hydrochloric acid, p-toluenesulfonic acid, and the like, and sulfuric acid and p-toluenesulfonic acid are preferable.

The amount of the acid catalyst used is, for example, in the range of from 0.01-fold molar equivalents to 10-fold molar equivalents, preferably in the range of from 0.2-fold molar equivalents to 2-fold molar equivalents, with respect to the amount of the carboxylic acid compound represented by Formula (V) used. The acid catalyst may be used in an amount appropriately selected within the above range.

The above halogenation reaction and esterification reaction may be carried out in the absence of a solvent or may be carried out in the presence of an inert solvent.

The inert solvent is not particularly limited as long as the solvent does not significantly inhibit the progress of the reaction. Examples of the inert solvent may include aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as dichloromethane, chloroform and carbon tetrachloride; N,N-dimethylformamide; and 1,3-dimethyl-2-imidazolidinon. These solvents may be used alone or as a mixture of two or more kinds thereof.

Among them, at least one member as an inert solvent selected from the group consisting of toluene and xylene can be particularly preferably used.

Concerning the amount of the inert solvent used, such a solvent may be used in an amount within the range of from 1-fold by mass to 15-fold by mass, and preferably within the range of from 1-fold by mass to 10-fold by mass, with respect to the amount of the carboxylic acid compound represented by Formula (V) used. The inert solvent may be used in an amount appropriately selected within the above range.

The reaction temperature in the above halogenation reaction and esterification reaction may be within the range of from −20° C. to 200° C., preferably within the range of from 20° C. to 120° C., and in the case of using an inert solvent, the reaction temperature may be any temperature that is lower than or equal to the boiling point. The reaction time may be appropriately selected within the range of from several minutes to 96 hours, and preferably within the range of from 30 minutes to 24 hours.

The above explained reaction conditions in the process c, such as type and amount of the halogenating agent, the acid catalyst, and the inert solvent, reaction temperature and reaction time of the halogenation reaction and esterification reaction, or the like are combinable in any arbitrary level, and each and every such combination is explicitly disclosed herein, as if each and every aspect was individually and explicitly recited.

In the process c as described above, the carboxylic acid derivative reproducing compound represented by Formula (IIIa), which is the aimed product, may be used in the process d with or without purification after completion of the reaction.

Then, the process d will be described.

The process d is a process of obtaining the imide compound represented by Formula (IV) by reacting the carboxylic acid derivative reproducing compound represented by Formula (IIIa) obtained in the process c and the aniline derivative represented by Formula (II) in the presence of a base.

In the process d, the imide compound represented by Formula (IV) is obtained by allowing to perform the reaction between the carboxylic acid derivative reproducing compound represented by Formula (IIIa) in place of the carboxylic acid derivative represented by Formula (III) and the aniline derivative represented by Formula (II), or between the carboxylic acid derivative reproducing compound represented by Formula (IIIa) together with the carboxylic acid derivative represented by Formula (III) and the aniline derivative represented by Formula (II), in the presence of a base in the same manner as in the process a.

The reaction conditions in the process d (type and amount of bases, reaction, type and amount used of inert solvents, reaction temperature, reaction time, etc.) are the same as those in the process a. However, the reaction conditions in the process d may be different from those in the process a.

In the case of using the carboxylic acid derivative reproducing compound represented by Formula (IIIa) together with the carboxylic acid derivative represented by Formula (III) in the process d, the amount of the carboxylic acid derivatives reproducing compound represented by Formula (IIIa) used may be from 1% by mass to 100% by mass, and is preferably from 1% by mass to 90% by mass, with respect to the total amount of the carboxylic acid derivative represented by Formula (III) and the carboxylic acid derivative reproducing compound represented by Formula (IIIa) used.

Then, the process e will be described.

The process e is a process of obtaining the aromatic amide derivative represented by Formula (I) in the same manner as in the process b, by hydrolyzing the imide compound represented by Formula (IV) obtained in the process d.

The reaction conditions in the process e (type and amount of bases or acids used in the hydrolysis, reaction, type and amount used of inert solvents, reaction temperature, reaction time, etc.) are the same as those in the process b. However, the reaction conditions in the process e may be different from those in the process b.

The aromatic amide derivative represented by Formula (I) obtained in the process e may be isolated in the same manner as in the process b from the reaction system after the completion of the reaction, according to a conventional method, and, if necessary, purification may be carried out by an operation such as recrystallization, column chromatography, or distillation.

In the process e, the carboxylic acid compound represented by Formula (V) is obtained together with the aromatic amide derivative represented by Formula (I) by hydrolyzing the imide compound represented by Formula (IV).

As with the process b, in the case of using an acid for hydrolysis, the carboxylic acid compound represented by Formula (V) may be isolated by filtration after the completion of the reaction. In the case of using a base for hydrolysis, the carboxylic acid compound represented by Formula (V) may be isolated by subjecting the aqueous phase to acid precipitation, followed by filtration. The isolated carboxylic acid compound may be optionally purified by an operation such as recrystallization and column chromatography.

The carboxylic acid compound represented by Formula (V) obtained in the process e can be used as a raw material for the reaction in the process c. That is, the reactions of from the process c to the process e may be repeated by using the carboxylic acid compound represented by Formula (V) as a raw material and using the resulting carboxylic acid derivative reproducing compound represented by Formula (IIIa) as a raw material for the reaction with the aniline derivative represented by Formula (II) in the process d.

The number of repeated reactions is not particularly limited and may be appropriately determined to be, for example, within a range of from one time to 1000 times, preferably within a range of from one time to 500 times, in consideration of the type and amount of by-products accumulated in the repeated reaction system, the reaction yield of each reaction process, the quality of the resulting aromatic amide derivative represented by Formula (I), and the like.

Each process through process a to process e is combinable in any arbitrary level within the reaction conditions explained above, and each and every such combination is explicitly disclosed herein, as if each and every aspect was individually and explicitly recited.

Typical compounds of the imide compound represented by Formula (IV), which are effective intermediates of the invention, will be exemplified below. However the invention is not limited to these compounds.

Incidentally, in the exemplified compounds shown below, “Me” represents a methyl group, “Et” represents an ethyl group, “Pr” represents a propyl group, “H” represents a hydrogen atom, “F” represents a fluorine atom, “Cl” represents a chlorine atom, “Br” represents a bromine atom, “I” represents an iodine atom, and “CF 3 ” represents a trifluoromethyl group, respectively.

Although representative compounds of the aromatic amide derivatives represented by Formula (I) of the invention are illustrated below, the invention is not limited to these compounds.

Incidentally, in the illustrated compounds shown below, “Me” represents a methyl group, “Et” represents an ethyl group, “Pr” represents a propyl group, “H” represents a hydrogen atom, “F” represents a fluorine atom, “Cl” represents a chlorine atom, “Br” represents a bromine atom, “I” represents an iodine atom, and “CF 3 ” represents a trifluoromethyl group, respectively

The imide compounds represented by Formula (IV), which are obtained by the method of producing an aromatic amide derivative of the invention, are extremely useful as intermediates in the method of producing an amide derivative that exhibits excellent efficacy in terms of pest controlling effects.

Hereinafter, the present invention is further explained in more detail with reference to Examples; however it should be construed that the invention is by no means limited thereto.

Note that the chemical shift values of 1 H-NMR are expressed in ppm unit at the lower magnetic field side on the basis of tetramethylsilane, “s” means a singlet, “d” means a doublet, “t” means a triplet, “m” means a multiplet, and “brs” means a broad singlet. Further, unless otherwise specifically stated, “parts” and “%” are expressed in terms of mass basis.

Reference Example 1

Synthesis of N-[2-fluoro-3-[benzoyl(methyl)amino]benzoyl]-3-[benzoyl(methyl)amino]-N-[2-bromo-4-(heptafluoroisopropan-2-yl)-6-(trifluoromethyl)phenyl]-2-fluorobenzamide (Compound No.: 1-123)

1.00 g of 2-bromo-4-(heptafluoroisopropan-2-yl)-6-(trifluoromethyl)aniline, 0.89 g of triethylamine, 0.03 g of N,N-dimethyl-4-aminopyridine, and 1.57 g of 2-fluoro-3-(N-methylbenzamide)benzoyl chloride were added to 4.00 g of 1,3-dimethyl-2-imidazolidinon, and the mixture was stirred at room temperature for 1 hour. The resulting reaction solution was extracted with ethyl acetate, washed with saturated brine, and the organic phase was dried over magnesium sulfate. After filtering off the magnesium sulfate, the solution was concentrated and purified by silica gel chromatography to obtain 2.20 g of the aimed imide compound (Compound No.: 1-123) (isolation yield: 97%) as a white solid.

The 1 H-NMR chemical shift values of the obtained imide compound are shown below.

1 H-NMR (DMSO-d 6 , 70° C.) δppm: 8.44 (s, 1H), 7.99 (s, 1H), 7.60-7.57 (m, 2H), 7.51 (brs, 2H), 7.30-7.18 (m, 12H), 3.12 (s, 6H)

MS (M+H) + =918, 920

Reference Example 2

Synthesis of N-[2-fluoro-3-[benzoyl(methyl)amino]benzoyl]-3-[benzoyl(methyl)amino]-N-[2-bromo-4-(heptafluoroisopropan-2-yl)-6-(trifluoromethyl)phenyl]-2-fluorobenzamide (Compound No.: 1-123)

2.16 g of the aimed imide compound (Compound No. 1-123) (isolation yield: 95%) was obtained as a white solid in the same procedure as in Reference Example 1, except that the reaction solvent was changed to 3.00 g of toluene in place of 4.00 g of 1,3-dimethyl-2-imidazolidinon and the reaction condition was changed to stirring at 90° C. for 4 hours in place of stirring at room temperature for 1 hour.

Reference Example 3

Synthesis of N-[2-fluoro-3-[benzoyl(methyl)amino]benzoyl]-3-[benzoyl(methyl)amino]-N-[4-(heptafluoroisopropan-2-yl)-2-iodo-6-(trifluoromethyl)phenyl]-2-fluorobenzamide (Compound No.: 1-124)

3.79 g of 4-(heptafluoroisopropan-2-yl)-2-iodo-6-(trifluoromethyl)aniline, 2.80 g of triethylamine, 0.06 g of N,N-dimethyl-4-aminopyridine, and 5.3 g of 2-fluoro-3-(N-methylbenzamido)benzoyl chloride were added to 7.6 g of toluene, and the mixture was stirred at 90° C. for 2 hours. The resulting reaction solution was cooled to room temperature, and the crystal precipitated upon addition of water was filtered off and washed sequentially with toluene and water to obtain 5.87 g (isolation yield: 73%) of the aimed imide compound (Compound No. 1-124) as a pale yellow solid.

The 1 H-NMR chemical shift values of the obtained imide compound are shown below.

1 H-NMR (DMSO-d 6 , 70° C.) δppm: 8.53 (s, 1H), 7.97 (s, 1H), 7.54-7.51 (m, 4H), 7.30-7.13 (m, 12H), 3.14 (s, 6H)

MS (M+H) + =966

Reference Example 4

Synthesis of N-[2-fluoro-3-[4-fluorobenzoyl(methyl)amino]benzoyl]-3-[4-fluorobenzoyl(methyl)amino]-N-[2-bromo-4-(heptafluoroisopropan-2-yl)-6-(trifluoromethyl)phenyl]-2-fluorobenzamide (Compound No.: 1-127)

The aimed imide compound (Compound No. 1-127) was synthesized by the same synthetic method as in Reference Example 1, except that 2-bromo-4-(heptafluoroisopropan-2-yl)-6-(trifluoromethyl)aniline was changed to 4-(heptafluoroisopropan-2-yl)-2-bromo-6-(trifluoromethyl)aniline, and 2-fluoro-3-(N-methylbenzamido)benzoyl chloride was changed to 2-fluoro-3-[4-fluorobenzoyl(methyl)amino]benzoyl chloride.

The 1 H-NMR chemical shift values of the obtained imide compound are shown below.

1 H-NMR (DMSO-d 6 , 70° C.)) δppm: 8.44 (s, 1H), 7.97 (s, 1H), 7.64-7.62 (m, 2H), 7.50 (brs, 2H), 7.28-7.24 (m, 6H), 7.00-6.96 (m, 4H), 3.15 (s, 6H)

MS (M+H) + =954, 956

Reference Example 5

Synthesis of N-[2-fluoro-3-[4-fluorobenzoyl(methyl)amino]benzoyl]-3-[4-fluorobenzoyl(methyl)amino]-N-[4-(heptafluoroisopropan-2-yl-)-2-iodo-6-(trifluoromethyl)phenyl]-2-fluorobenzamide (Compound No.: 1-128)

The aimed imide compound (Compound No. 1-128) was synthesized by the same synthetic method as in Reference Example 1, except that 2-bromo-4-(heptafluoroisopropan-2-yl)-6-(trifluoromethyl)aniline was changed to 4-(heptafluoroisopropan-2-yl)-2-iodo-6-(trifluoromethyl)aniline, and 2-fluoro-3-(N-methylbenzamido)benzoyl chloride was changed to 2-fluoro-3-[4-fluorobenzoyl(methyl)amino]benzoyl chloride.

The 1 H-NMR chemical shift values of the obtained imide compound are shown below.

1 H-NMR (DMSO-d 6 , 70° C.)) δppm: 8.53 (s, 1H), 7.95 (s, 1H), 7.59-7.57 (m, 2H), 7.48 (brs, 2H), 7.28-7.22 (m, 6H), 7.01-6.97 (m, 4H), 3.16 (s, 6H)

MS (M+H) + =1002

Reference Example 6

Synthesis of N-[2-fluoro-3-[2,6-difluorobenzoyl(methyl)amino]benzoyl]-3-[2,6-difluorobenzoyl(methyl)amino]-N-[2-bromo-4-(heptafluoroisopropan-2-yl-)-6-(trifluoromethyl)phenyl]-2-fluorobenzamide (Compound No.: 1-135)

The aimed imide compound (Compound No. 1-135) was synthesized by the same synthetic method as in Reference Example 1, except that 2-bromo-4-(heptafluoroisopropan-2-yl)-6-(trifluoromethyl)aniline was changed to 4-(heptafluoroisopropan-2-yl)-2-bromo-6-(trifluoromethyl)aniline, and 2-fluoro-3-(N-methylbenzamido)benzoyl chloride was changed to 2-fluoro-3-[2,6-difluorobenzoyl(methyl)amino]benzoyl chloride.

The 1 H-NMR chemical shift values of the obtained imide compound are shown below.

1 H-NMR (DMSO-d 6 , 70° C.)) δppm: 8.46 (s, 1H), 8.01 (s, 1H), 7.33-7.30 (m, 4H), 7.25-7.11 (m, 5H), 6.86 (brs, 3H), 3.17 (s, 6H)

MS (M+H) + =990, 992

Reference Example 7

Synthesis of N-[2-fluoro-3-[4-nitrobenzoyl(methyl)amino]benzoyl]-3-[4-nitrobenzoyl(methyl)amino]-N-[2-bromo-4-(heptafluoroisopropan-2-yl)-6-(trifluoromethyl)phenyl]-2-fluorobenzamide (Compound No.: 1-577)

The aimed imide compound (Compound No. 1-577) was synthesized by the same synthetic method as in Reference Example 1, except that 2-bromo-4-(heptafluoroisopropan-2-yl)-6-(trifluoromethyl)aniline was changed to 4-(heptafluoroisopropan-2-yl)-2-bromo-6-(trifluoromethyl)aniline, and 2-fluoro-3-(N-methylbenzamido)benzoyl chloride was changed to 2-fluoro-3-[4-nitrobenzoyl(methyl)amino]benzoyl chloride.

The 1 H-NMR chemical shift values of the obtained imide compound are shown below.

1 H-NMR (DMSO-d 6 , 70° C.)) δppm: 8.41 (s, 1H), 8.03-8.01 (m, 4H), 7.92 (s, 1H), 7.72-7.70 (m, 6H), 7.30-7.24 (m, 2H), 3.20 (s, 6H)

MS (M+Na) + =1030, 1032

Reference Example 8

Synthesis of N-[2-fluoro-3-[4-nitrobenzoyl(methyl)amino]benzoyl]-3-[4-nitrobenzoyl(methyl)amino]-N-[4-(heptafluoroisopropan-2-yl)-2-iodo-6-(trifluoromethyl)phenyl]-2-fluorobenzamide (Compound No.: 1-578)

The aimed imide compound (Compound No. 1-578) was synthesized by the same synthetic method as in Reference Example 1, except that 2-bromo-4-(heptafluoroisopropan-2-yl)-6-(trifluoromethyl)aniline was changed to 4-(heptafluoroisopropan-2-yl)-2-iodo-6-(trifluoromethyl)aniline, and 2-fluoro-3-(N-methylbenzamido)benzoyl chloride was changed to 2-fluoro-3-[4-nitrobenzoyl(methyl)amino]benzoyl chloride.

The 1 H-NMR chemical shift values of the obtained imide compound are shown below.

1 H-NMR (DMSO-d 6 , 70° C.) δppm: 8.49 (s, 1H), 8.03-8.02 (m, 4H), 7.92 (s, 1H), 7.70-7.67 (m, 2H), 7.49-7.48 (m, 4H), 7.25-7.24 (m, 2H), 3.21 (s, 6H)

MS (M+Na) + =1078

Reference Example 9

Synthesis of N-[2-fluoro-3-[benzoyl(methyl)amino]benzoyl]-3-[benzoyl(methyl)amino]-N-[2,4-bis(heptafluoroisopropan-2-yl)-6-(trifluoromethyl)phenyl]-2-fluorobenzamide (Compound No.: 1-246)

The aimed imide compound (Compound No. 1-246) was synthesized by the same synthetic method as in Reference Example 1, except that 2-bromo-4-(heptafluoroisopropan-2-yl)-6-(trifluoromethyl)aniline was changed to 2,4-bis(heptafluoroisopropan-2-yl)-6-(trifluoromethyl)aniline, and 2-fluoro-3-(N-methylbenzamide)benzoyl chloride was changed to 2-fluoro-3-[benzoyl(methyl)amino]benzoyl chloride.

The 1 H-NMR chemical shift values of the obtained imide compound are shown below.

1 H-NMR (DMSO-d 6 , 70° C.)) δppm: 8.48 (s, 1H), 8.07 (s, 1H), 7.57-7.54 (m, 2H), 7.34 (brs, 2H), 7.28-7.18 (m, 14H), 3.07 (s, 6H)

MS(M+H) + =1008

Reference Example 10

Synthesis of N-[2-fluoro-3-[benzoyl(methyl)amino]benzoyl]-3-[benzoyl(methyl)amino]-N-[4-bromo-2-(heptafluoroisopropan-2-yl)-6-(trifluoromethyl)phenyl]-2-fluorobenzamide (Compound No.: 1-240)

The aimed imide compound (Compound No. 1-240) was synthesized by the same synthetic method as in Reference Example 1, except that 2-bromo-4-(heptafluoroisopropan-2-yl)-6-(trifluoromethyl)aniline was changed to 2-(heptafluoroisopropan-2-yl)-4-bromo-6-(trifluoromethyl)aniline, and 2-fluoro-3-(N-methylbenzamido)benzoyl chloride was changed to 2-fluoro-3-[benzoyl(methyl)amino]benzoyl chloride.

The 1 H-NMR chemical shift values of the obtained imide compound are shown below.

1 H-NMR (DMSO-d 6 , 70° C.)) δppm: 8.52 (s, 1H), 8.09 (s, 1H), 7.51-7.48 (m, 2H), 7.28-7.26 (m, 2H), 7.21-7.19 (m, 12H), 3.08 (s, 6H)

MS (M+H) + =918, 920

Reference Example 11

Synthesis of N-[2-fluoro-3-[benzoyl(methyl)amino]benzoyl]-3-[benzoyl(methyl)amino]-N-[2,6-dibromo-4-(nonafluoro-sec-butyl)phenyl]-2-fluorobenzamide (Compound No.: 1-168)

The aimed imide compound (Compound No. 1-168) was synthesized by the same synthetic method as in Reference Example 1, except that 2-bromo-4-(heptafluoroisopropan-2-yl)-6-(trifluoromethyl)aniline was changed to 4-(nonafluoro-sec-butyl)-2,6-dibromoaniline, and 2-fluoro-3-(N-methylbenzamido)benzoyl chloride was changed to 2-fluoro-3-[benzoyl(methyl)amino]benzoyl chloride.

The 1 H-NMR chemical shift values of the obtained imide compound are shown below.

1 H-NMR (DMSO-d 6 , 70° C.) δppm: 7.95 (s, 2H), 7.61-7.58 (m, 2H), 7.50 (brs, 2H), 7.29-7.26 (m, 2H), 7.22-7.16 (m, 10H), 3.21 (s, 6H)

MS (M+Na) + =1000, 1002