JPH06199762A - Production of dibenzoylhydrazine derivative - Google Patents

Abstract

PURPOSE:To readily obtain the subject compound by reacting a hydrazine derivative with a carboxylic acid derivative. CONSTITUTION:A compound of formula I (R<1> to R<5> are H, halogen, cyano, etc.; R<6> is 3-12C alkyl; X is cyano, SCCl3, etc.) and a carboxylic acid of formula II (R<15> to R<19> have the same meanings as those of R<1> to R<5>) or a reactive derivative thereof are subjected to condensing reaction in a solvent (e.g. THF) at -100 to +100 deg.C for 1-48hr to afford the objective compound of formula III. The compound of formula II is used in an amount of 1-10 equiv. based on the compound of formula I. N-(5-Methyl-1,4-benzodioxan-6-carbo)-N-cyano-N'-t- butylhydrazine is exemplified as the compound of formula I and 3,5- dimethylbenzoyl chloride is exemplified as the compound of formula II. Furthermore, N-(5-methyl-1,4-benzodioxan-6-carbo)-N-cyano-N'-t-butyl-N'-(3,5- dimethylbenzoyl)hydrazine is exemplified as the compound of formula III.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing a dibenzoylhydrazine derivative.

[0002]

2. Description of the Related Art JP-A-2-108659, JP-A-2-207066 and JP-A-2-295963 disclose a method for producing a dibenzoylhydrazine derivative. It is a new one that is different from the manufacturing method of.

[0003]

The present invention has the general formula (II)

[0004]

[Chemical 5]

[Wherein R ¹ , R ² , R ³ , R ⁴ and R ⁵
Are the same or different, and are a hydrogen atom, halogen, cyano,
Hydroxy, C _1-6 alkyl, C _1-6 haloalkyl, C
_1-6 alkoxy, C _1-6 alkoxy C _1-6 alkyl, C
_1-6 alkoxy C _1-6 alkoxy, C _2-6 alkenyl,
C _2-6 alkynyl, carboxy, C _1-6 alkoxycarbonyl, C _1-6 alkylcarbonyl, group —NR ⁷ R ⁸ ,
Or a group —S (O) _m R ⁷ (R ⁷ and R ⁸ are the same or different and represent a hydrogen atom, C _1-6 alkyl or phenyl)
Or R ¹ and R ² , R ² and R ³ , R ³ and R
⁴ or R ⁴ and R ⁵ together form a group -A-CR ⁹ R
¹⁰ -CR ¹¹ R ¹² -B- or a group -A-CR ⁹ R ¹⁰ -B-
(A and B are the same or different and represent an oxygen atom, a sulfur atom or methylene, and R ⁹ , R ¹⁰ , R ¹¹ and R ¹² are the same or different and are a hydrogen atom, a halogen, a C _1-4 alkyl,
C _1-4 alkoxy), R ⁶ represents C _3-12 branched alkyl, X represents cyano, group —SCCl ₃ , group —S.
CCl ₂ F, group —S (O) _m NR ¹³ R ¹⁴ , group —S (O)
_m NR ¹³ CO ₂ R ¹⁴ , group —S (O) _m NR ¹³ COR ¹⁴ ,
Group ^{_{-S (O) m NR 13 SO}} 2 R 14, group -S (O) _m NR
¹³ COSR ¹⁴ , group —S (O) _m NR ¹³ SO ₂ N (R ¹⁴ ).
₂ , base

[0006]

[Chemical 6]

A group --COCO ₂ R ¹³ and a group --CH ₂ OCO
R ¹³ or a group —CONR ¹³ R ¹⁴ (in the above formula, m is 0,
1 or 2 and represents R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R
⁶ has the same meaning as above, and R ¹³ and R ¹⁴ are the same or different and each is a hydrogen atom, C _1-6 alkyl, or 1 to 3 C _1-4.
And phenyl and benzyl which may be substituted with alkyl or halogen, and R ^{15 to} R ¹⁹ have the same meanings as R ^{1 to} R ⁵ . ] The compound represented by the following general formula (III)

[0008]

[Chemical 7]

[Wherein R ¹⁵ , R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹
Indicates the same meaning as described above. ] It reacts with the carboxylic acid represented by these or its reactive derivative,
The following general formula (I)

[0010]

[Chemical 8]

[In the formula, R ^{1 to} R ⁶ , R ^{15 to} R ¹⁹ and X have the same meanings as described above. ] It is a manufacturing method of the dibenzoyl hydrazine derivative represented by these.

In the present invention, "halogen" means fluorine, chlorine, bromine and iodine.

In the present invention, "C _1-6 alkyl" means
For example, it is a linear or branched alkyl group having 1 to 6 carbon atoms such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, t-butyl, pentyl, hexyl and the like.

In the present invention, "C _1-6 haloalkyl" means, for example, chloromethyl, fluoromethyl, bromomethyl, methyl iodide, dichloromethyl, trichloromethyl, difluoromethyl, trifluoromethyl, chlorodifluoromethyl, 2-chloroethyl. , 2,2,2-trichloroethyl, 2-fluoroethyl, chloro-t-butyl, 2-chlorohexyl and the like, wherein 1 to 3 of the above halogens are substituted on the above C _1-6 alkyl.

In the present invention, "C _1-6 alkoxy" means, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, t-butoxy,
It is a linear or branched alkoxy group having 1 to 6 carbon atoms such as hexyloxy.

In the present invention, "C _1-6 alkoxy C _1-6
"Alkyl" means, for example, methoxymethyl, ethoxymethyl, butoxymethyl, t-butoxymethyl, 1-methoxyethyl, 2-methoxyethyl, 2-ethoxyethyl,
2-hexyloxyethyl, 4-butoxybutyl, 3-
The C _1-6 alkoxy such as methoxyhexyl is the C
It is a group in which _1-6 alkyl is substituted.

In the present invention, "C _1-6 alkoxy C _1-6
"Alkoxy" is, for example, methoxymethoxy, ethoxymethoxy, t-butoxymethoxy, hexyloxymethoxy, 1-methoxyethoxy, 2-methoxyethoxy, 2-ethoxyethoxy, 2-methoxy-1,1-dimethylethoxy, 6-. The above C _1-6 alkoxy such as methoxyhexyloxy is a group in which one C _1-6 alkoxy is substituted.

In the present invention, "C _2-6 alkenyl" means, for example, vinyl, propenyl, 2-methyl-1-propenyl, allyl, 1-butynyl, 2-methyl-1-butynyl, 2-hexenyl and the like. It is a linear or branched alkenyl group having 2 to 6 carbon atoms.

In the present invention, "C _2-6 alkynyl" means, for example, ethynyl, propynyl, 2-propynyl,
It is a linear or branched alkynyl group having 2 to 6 carbon atoms such as 1-hexynyl.

[0020] In the present invention, the "C _1-6 alkoxycarbonyl", for example, methoxycarbonyl, ethoxycarbonyl, propyloxycarbonyl, isopropyloxycarbonyl, butoxycarbonyl, t-butoxycarbonyl, hexyl oxycarbonyl, wherein the C _{1 -6}
A group in which alkoxy is substituted with carbonyl.

In the present invention, "C _1-6 alkylcarbonyl" means, for example, acetyl, propionyl, isopropionyl, pivaloyl, butyryl, hexanoyl and the like.
It is a group in which the C _1-6 alkyl is substituted with carbonyl.

In the present invention, "C _1-4 alkyl" means
For example, it is a linear or branched alkyl group having 1 to 4 carbon atoms such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl and the like.

In the present invention, "C _1-4 alkoxy" means, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, t-butoxy, etc., straight or branched chain having 1 to 4 carbon atoms. It is an alkoxy group in the chain.

In the present invention, "C _3-12 branched alkyl" means, for example, isopropyl, t-butyl, 1,2,2-
Trimethylpropyl, 2,2-dimethylpropyl, 1,
It is a branched chain alkyl group having 3 to 12 carbon atoms such as 2,2-trimethylbutyl. The production method of the present invention and the production method of the raw materials thereof are represented by the following reaction formulas.

[0025]

[Chemical 9]

[Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ ,
^{R 6, R 15, R 16} , R 17, R 18, R 19 and X are as defined above] Step A was formylated nitrogen atom of benzohydrazide of formula (VII) are known per se, It is a step of producing a hydrazine derivative of the formula (V).

Examples of the compound of formula (VII) include:
N-benzoyl-N'-t-butylhydrazine, N-benzoyl-N '-(1,2,2-trimethylpropyl)
Hydrazine, N-benzoyl-N '-(2,2-dimethylpropyl) hydrazine, N- (4-ethylbenzoyl) -N'-t-butylhydrazine, N- (4-ethylbenzoyl) -N'-(1 , 2,2-Trimethylpropyl) hydrazine, N- (4-ethylbenzoyl) -N '
-(2,2, -Dimethylpropyl) hydrazine, N-
(2,3-Dimethylbenzoyl) -N'-t-butylhydrazine, N- (1,4-benzodioxane-6-carbo) -N'-t-butylhydrazine, N- (5-methyl-1,4) -Benzodioxane-6-carbo) -N'-t
-Butylhydrazine, N- (5-methyl-1,4-benzodioxane-6-carbo) -N '-(1,2,2-trimethylpropyl) hydrazine, N- (5-methyl-
1,4-benzodioxane-6-carbo) -N'-
(2,2-Dimethylpropyl) hydrazine, N- (5-
Examples thereof include methylchroman-6-carbo) -N′-t-butylhydrazine, but are not limited thereto.

Examples of the compound of the formula (V) include N-
Benzoyl-N'-t-butyl-N'-formylhydrazine, N- (4-ethylbenzoyl) -N'-t-butyl-N'-formylhydrazine, N- (2,3-dimethylbenzoyl) -N '-T-butyl-N'-formylhydrazine, N- (1,4-benzodioxane-6-carbo) -N'-t-butyl-N'-formylhydrazine,
N- (5-methyl-1,4-benzodioxane-6-carbo) -N'-t-butyl-N'-formylhydrazine, N- (5-methyl-1,4-benzodioxane-6)
-Carbo) -N '-(1,2,2-trimethylpropyl) -N'-formylhydrazine, N- (5-methyl-
1,4-benzodioxane-6-carbo) -N'-
(2,2-Dimethylpropyl) -N'-formylhydrazine, N- (5-methylchroman-6-carbo) -N '
-T-butyl-N'-formylhydrazine, N- (5-
Methylchroman-6-carbo) -N '-(1,2,2-
Trimethylpropyl) -N'-formylhydrazine, N
-(5-methylchroman-6-carbo) -N '-(2,
2-dimethylpropyl) -N′-formylhydrazine and the like can be mentioned, but the invention is not limited thereto.

In the formylation reaction, the formylating agent is not particularly limited as long as it is one usually used for formylating a nitrogen atom. For example, formic acid-
Acetic anhydride, formic acid-dicyclohexylcarbodiimide-pyridine, N, N-dimethylformamide-silica gel,
Examples thereof include ethyl formate, pentafluorophenyl formate, t-butyldimethylsilyl chloride-N, N-dimethylaminopyridine-triethylamine-N, N-dimethylformamide and the like.

The formylating agent is usually used in the amount of 1 equivalent to excess amount based on compound (VII). The reaction is carried out without solvent or in a solvent. The solvent is not particularly limited as long as it does not participate in the reaction, for example, hexane, petroleum ether, benzene, toluene, xylene, chloroform,
Hydrocarbons such as methylene chloride and o-chlorobenzene, ethers such as diethyl ether, tetrahydrofuran, dioxane, ethylene glycol dimethyl ether and the like can be mentioned.

The reaction temperature is usually -100 ° C to 150 ° C,
The temperature is preferably −78 ° C. to 100 ° C., and the time required for the reaction is usually 30 minutes to 1 week.

In step B, the hydrazine derivative of formula (V)
General formula (VI)

[0033]

[Image Omitted] X-L [wherein X represents the same meaning as described above, and L represents a leaving group such as a halogen atom], and a hydrazine derivative of the formula (IV) is obtained. This is a manufacturing process.

Examples of the compound of formula (VI) include cyanogen bromide, cyanogen chloride, trichloromethanesulfenyl chloride, dichlorofluoromethanesulfenyl chloride, N, N-dimethylsulfenamoyl chloride, N,
N-dibutylsulfenamoyl chloride, N-ethyl-
N-methylsulfenamoyl chloride, N, N-dibutylsulfinamoyl chloride, N, N-dibutylsulfamoyl chloride, N-ethyl-N-methoxycarbonylsulfenamoyl chloride, N-methyl-N-butoxycarbonylsulfate Phenamoyl chloride, N-methyl-
N-butoxycarbonylsulfinamoyl chloride, N
-Methyl-N-butoxycarbonylsulfamoyl chloride, N-isopropyl-N-isopropoxycarbonylsulfenamoyl chloride, N-butyl-N-butoxycarbonylsulfenamoyl chloride, N-methyl-
N-acetylsulfenamoyl chloride, N-methyl-
N-methanesulfonylsulfenamoyl chloride, N
-Methyl-N-benzenesulfonylsulfenamoyl chloride, N-methyl-N-methylthiocarbonylsulfenamoyl chloride, N- (2,4-dichlorophenyl) -N-benzylthiocarbonylsulfenamoyl chloride, N-methyl-N -(N ', N'-dimethylsulfamoyl) sulfenamoyl chloride, ethyloxalyl chloride, t-butyloxalyl chloride, chloromethyl pivalate, N, N-dimethylcarbamoyl chloride and the like can be mentioned. It is not limited.

Examples of the compound of formula (IV) include N
-Benzoyl-N-cyano-N'-t-butyl-N'-
Formylhydrazine, N- (4-ethylbenzoyl)-
N-cyano-N'-t-butyl-N'-formylhydrazine, N- (2,3-dimethylbenzoyl) -N-cyano-N'-t-butyl-N'-formylhydrazine, N
-(5-Methyl-1,4-benzodioxane-6-carbo) -N-cyano-N'-t-butyl-N'-formylhydrazine, N- (5-methyl-1,4-benzodioxane-6 -Carbo) -N-cyano-N '-(1,2,2
-Trimethylpropyl) -N'-formylhydrazine,
N- (5-methyl-1,4-benzodioxane-6-carbo) -N-cyano-N '-(2,2-dimethylpropyl) -N'-formylhydrazine, N- (5-methylchroman-6) -Carbo) -N-cyano-N'-t-butyl-N'-formylhydrazine, N- (5-methyl-1,
4-benzodioxane-6-carbo) -N-trichloromethanesulfenyl-N'-t-butyl-N'-formylhydrazine, N- (5-methyl-1,4-benzodioxane-6-carbo) -N -Dichlorofluoromethanesulfenyl-N'-t-butyl-N'-formylhydrazine, N- (5-methyl-1,4-benzodioxane-
6-carbo) -N- (N ", N" -dibutylsulfenamoyl) -N'-t-butyl-N'-formylhydrazine, N- (5-methyl-1,4-benzodioxane-6) -Carbo) -N- (N "-methyl-N" -butoxycarbonylsulfenamoyl) -N'-t-butyl-N'-formylhydrazine, N- (5-methyl-1,
4-Benzodioxane-6-carbo) -N- (N ''-
Methyl-N ″ -butoxycarbonylsulfenamoyl) -N ′-(1,2,2-trimethylpropyl)-
N'-formylhydrazine, N- (5-methylchroman-6-carbo) -N- (N "-methyl-N" -butoxycarbonylsulfenamoyl) -N'-t-butyl-N'-formyl Hydrazine, N- (5-methyl-1,
4-Benzodioxane-6-carbo) -N- (N ''-
Isopropyl-N "-isopropoxycarbonylsulfenamoyl) -N'-t-butyl-N'-formylhydrazine, N- (5-methylchroman-6-carbo)-
N- (N "-isopropyl-N" -isopropoxycarbonylsulfenamoyl) -N'-t-butyl-
N'-formylhydrazine, N- (5-methyl-1,4
-Benzodioxan-6-carbo) -N- (N "-methyl-N" -benzenesulfonylsulfonylphenamoyl) -N'-t-butyl-N'-formylhydrazine,
N- (5-methyl-1,4-benzodioxane-6-carbo) -N- (N ''-2,4-dichlorophenyl-
N ″ -benzylthiocarbonylsulfenamoyl)-
N'-t-butyl-N'-formylhydrazine, N-
(5-Methyl-1,4-benzodioxane-6-carbo) -N- [N "-methyl-N"-(N "',
N "'-dimethylsulfamoyl) sulfenamoyl] -N'-t-butyl-N'-formylhydrazine,
N- (5-methyl-1,4-benzodioxane-6-carbo) -N-ethoxalyl-N'-t-butyl-N'-
Formylhydrazine, N- (5-methyl-1,4-benzodioxane-6-carbo) -N-pivaloyloxymethyl-N'-t-butyl-N'-formylhydrazine,
N- (5-methyl-1,4-benzodioxane-6-carbo) -N- (N ", N" -dimethylcarbamoyl) -N'-t-butyl-N'-formylhydrazine and the like can be mentioned. However, the present invention is not limited to this.

The compound (VI) is 1 with respect to the compound (V).
Equivalent to 20 equivalents, preferably 1 equivalent to 5 equivalents are used.

The reaction is preferably carried out in the presence of a base. Examples of the base used include triethylamine, N, N-dimethylaniline, pyridine, 4-dimethylaminopyridine, 1,5-diazabicyclo [4.3.
0] nonene-5 (DBN), 1,8-diazabicyclo [5.4.0] undecene-7 (DBU), n-butyllithium, sec-butyllithium, t-butyllithium, and other organic bases and potassium carbonate, Inorganic bases such as sodium carbonate, potassium hydroxide, sodium hydride and the like can be mentioned.

The base is usually used in an amount of 1 to 20 equivalents.

The reaction is usually carried out in a solvent. Examples of the solvent used include hexane, benzene, toluene, methylene chloride, chloroform, diethyl ether, tetrahydrofuran, dioxane, acetone, methyl ethyl ketone, acetonitrile, ethyl acetate, N, N.
-Dimethylformamide, N, N-dimethylacetamide, dimethylsulfoxide and the like are not particularly limited as long as they do not participate in this reaction.

The reaction temperature is usually -100 ° C to 150 ° C,
The temperature is preferably −78 ° C. to 100 ° C., and the time required for the reaction is usually 1 hour to 48 hours.

Step C is a step of removing the formyl group of the compound of formula (IV) to produce a hydrazine derivative of formula (II).

Examples of the compound of formula (II) include N
-Benzoyl-N-cyano-N'-t-butylhydrazine, N- (4-ethylbenzoyl) -N-cyano-N '
-T-butylhydrazine, N- (2,3-dimethylbenzoyl) -N-cyano-N'-t-butylhydrazine,
N- (5-methyl-1,4-benzodioxane-6-carbo) -N-cyano-N'-t-butylhydrazine, N
-(5-Methyl-1,4-benzodioxane-6-carbo) -N-cyano-N '-(1,2,2-trimethylpropyl) hydrazine, N- (5-methyl-1,4-benzodioxane -6-carbo) -N-cyano-N'-
(2,2-Dimethylpropyl) hydrazine, N- (5-
Methylchroman-6-carbo) -N-cyano-N'-t
-Butylhydrazine, N- (5-methyl-1,4-benzodioxane-6-carbo) -N-trichloromethanesulfenyl-N'-t-butylhydrazine, N- (5-
Methyl-1,4-benzodioxane-6-carbo) -N
-Dichlorofluoromethanesulfenyl-N'-t-butylhydrazine, N- (5-methyl-1,4-benzodioxane-6-carbo) -N- (N ", N" -dibutylsulfenamoyl) -N'-t-butylhydrazine, N- (5-methyl-1,4-benzodioxane-6
-Carbo) -N- (N "-methyl-N" -butoxycarbonylsulfenamoyl) -N'-t-butylhydrazine, N- (5-methyl-1,4-benzodioxane-6-carbo) -N- (N "-methyl-N" -butoxycarbonylsulfenamoyl) -N '-(1,2,
2-trimethylpropyl) hydrazine, N- (5-methylchroman-6-carbo) -N- (N ''-methyl-
N "-butoxycarbonylsulfenamoyl) -N '
-T-butylhydrazine, N- (5-methyl-1,4-
Benzodioxane-6-carbo) -N- (N "-isopropyl-N" -isopropoxycarbonylsulfenamoyl) -N'-t-butylhydrazine, N- (5-
Methylchroman-6-carbo) -N- (N "-isopropyl-N" -isopropoxycarbonylsulfenamoyl) -N'-t-butylhydrazine, N- (5-methyl-1,4-benzodioxane -6-carbo) -N-
(N "-methyl-N" -benzenesulfonylsulfenamoyl) -N'-t-butylhydrazine, N-
(5-Methyl-1,4-benzodioxane-6-carbo) -N- (N ''-2,4-dichlorophenyl-
N ″ -benzylthiocarbonylsulfenamoyl)-
N'-t-butylhydrazine, N- (5-methyl-1,
4-benzodioxane-6-carbo) -N- [N ''-
Methyl-N ″-(N ′ ″, N ′ ″-dimethylsulfamoyl) sulfenamoyl] -N′-t-butylhydrazine, N- (5-methyl-1,4-benzodioxane-6-carbo ) -N-Ethoxalyl-N'-t-butylhydrazine, N- (5-methyl-1,4-benzodioxane-6-carbo) -N-pivaloyloxymethyl-
N'-t-butylhydrazine, N- (5-methyl-1,
4-benzodioxane-6-carbo) -N- (N '',
Examples thereof include N ″ -dimethylcarbamoyl) -N′-t-butylhydrazine, but the invention is not limited thereto.

Deformylation can be achieved with an inorganic acid such as hydrochloric acid or sulfuric acid, an inorganic base such as potassium hydroxide or potassium carbonate, and the preferred one is hydrochloric acid.

The amount of the acid or base used is usually an excess amount, preferably about 1 to 100 equivalents.

The deformylation reaction is preferably carried out in the presence of a solvent, but the solvent is not particularly limited as long as the reaction has no side effect. Suitable solvents include, for example, water, ethanol, methanol, tetrahydrofuran, dioxane, diethyl ether, acetonitonyl, methylene chloride, chloroform, benzene, toluene and mixtures of these solvents.

The reaction temperature is usually 0 ° C to 100 ° C,
The time required for the reaction is usually 30 minutes to 48 hours.

In step D, the hydrazine derivative of the formula (II) is converted into the following formula (III)

[0048]

[Chemical 11]

[In the formula, R ¹⁵ , R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹
Has the same meaning as above. ] It is a process of manufacturing the dibenzoyl hydrazine derivative of formula (I) by making it react with the carboxylic acid or its reactive derivative.

Examples of the compound of formula (I) include N-
Benzoyl-N-cyano-N'-t-butyl-N'-benzoylhydrazine, N- (4-ethylbenzoyl)-
N-cyano-N'-t-butyl-N '-(3,5-dimethylbenzoyl) hydrazine, N- (2,3-dimethylbenzoyl) -N-cyano-N'-t-butyl-N'-
(3,5-Dimethylbenzoyl) hydrazine, N- (5
-Methyl-1,4-benzodioxan-6-carbo)-
N-cyano-N'-t-butyl-N '-(3,5-dimethylbenzoyl) hydrazine, N- (5-methyl-1,
4-benzodioxan-6-carbo) -N-cyano-
N'-t-butyl-N '-(3,5-dichlorobenzoyl) hydrazine, (5-methyl-1,4-benzodioxane-6-carbo) -N-cyano-N'-t-butyl-
N '-(2,4-dichlorobenzoyl) hydrazine, N
-(5-Methyl-1,4-benzodioxane-6-carbo) -N-cyano-N '-(1,2,2-trimethylpropyl) -N'-(3,5-dimethylbenzoyl) hydrazine, N -(5-Methyl-1,4-benzodioxane-6-carbo) -N-cyano-N '-(2,2-dimethylpropyl) -N'-(3,5-dimethylbenzoyl)
Hydrazine, N- (5-methylchroman-6-carbo)
-Cyano-N'-t-butyl-N '-(3,5-dimethylbenzoyl) hydrazine, N- (5-methyl-1,4)
-Benzodioxane-6-carbo) -N-trichloromethanesulfenyl-N'-t-butyl-N '(3,5-
Dimethylbenzoyl) hydrazine, N- (5-methyl-
1,4-benzodioxane-6-carbo) -N-dichlorofluoromethanesulfenyl-N'-t-butyl-
N '-(3,5-dimethylbenzoyl) hydrazine, N
-(5-Methyl-1,4-benzodioxane-6-carbo) -N- (N ", N" -dibutylsulfenamoyl) -Nt-butyl-N '-(3,5-dimethyl Benzoyl) hydrazine, N- (5-methyl-1,4-benzodioxane-6-carbo) -N-(-N "-methyl-N" -butoxycarbonylsulfenamoyl)-
N'-t-butyl-N '-(3,5-dimethylbenzoyl) hydrazine, N- (5-methyl-1,4-benzodioxane-6-carbo) -N- (N''-methyl-
N "-butoxycarbonylsulfenamoyl) -N '
-T-butyl-N '-(3,5-dichlorobenzoyl)
Hydrazine, N- (5-methyl-1,4-benzodioxane-6-carbo) -N- (N "-methyl-N"-
Butoxycarbonylsulfenamoyl) -N '-(1,
2,2-trimethylpropyl) -N '-(3,5-dimethylbenzoyl) hydrazine, N- (5-methylchroman-6-carbo) -N- (N "-methyl-N" -butoxycarbonylsul Phenamoyl) -N'-t-butyl-N '-(3,5-dimethylbenzoyl) hydrazine, N- (5-methyl-1,4-benzodioxane-6)
-Carbo) -N- (N "-isopropyl-N" -isopropoxycarbonylsulfenamoyl) -N'-t
-Butyl-N '-(3,5-dimethylbenzoyl) hydrazine, N- (5-methylchroman-6-carbo) -N
-(N "-isopropyl-N" -isopropoxycarbonylsulfenamoyl) -N'-t-butyl-N '
-(3,5-Dimethylbenzoyl) hydrazine, N-
(5-Methyl-1,4-benzodioxane-6-carbo) -N- (N "-methyl-N" -benzenesulfonylsulfonylphenamoyl) -N'-t-butyl-N'-
(3,5-Dimethylbenzoyl) hydrazine, N- (5
-Methyl-1,4-benzodioxan-6-carbo)-
N- (N "-2,4-dichlorophenyl-N" -benzylthiocarbonylsulfenamoyl) -N'-t-
Butyl-N '-(3,5-dimethylbenzoyl) hydrazine, N- (5-methyl-1,4-benzodioxane-
6-carbo) -N- [N "-methyl-N"-
(N ''',N'''-dimethylsulfamoyl) sulfenamoyl] -N'-t-butyl-N '-(3,5-
Dimethylbenzoyl) hydrazine, N- (5-methyl-
1,4-benzodioxane-6-carbo) -N-ethoxalyl-N'-t-butyl-N '-(3,5-dimethylbenzoyl) hydrazine, N- (5-methyl-1,4-
Benzdioxane-6-carbo) -N-pivaloyloxymethyl-N'-t-butyl-N '-(3,5-dimethylbenzoyl) hydrazine, N- (5-methyl-1,4)
-Benzodioxan-6-carbo) -N- (N '',
N ″ -dimethylcarbamoyl) -N′-t-butyl-
Examples thereof include N ′-(3,5-dimethylbenzoyl) hydrazine, but the present invention is not limited thereto.

This step D is a condensation reaction of the hydrazine derivative of the formula (II) and the carboxylic acid of the formula (III), and is therefore carried out by a known method known per se as a condensation reaction.

When using the carboxylic acid (III) itself, it is preferable to use dichlorohexylcarbodiimide (D
CC), diethylazocarboxylate-triphenylphosphine (Mitsunobu reagent), p-toluenesulfonic acid,
A dehydrating agent such as sulfuric acid is used. When DCC is used, pyridine, 4-pyrrolidinopyridine, 4-dimethylaminopyridine and the like are more preferably used together.

Examples of the reactive derivative of carboxylic acid (III) include acid halides (acid chloride, acid bromide, acid iodide, etc.), acid anhydrides, mixed acid anhydrides, active esters (eg p-nitrobenzyl ester). Examples thereof include those commonly used in condensation reactions such as active amides.

When a reactive derivative of carboxylic acid (III) is used, pyridine, triethylamine, 4-dimethylaminopyridine, 1,5-diazabicyclo [4.
3.0] Nonene-5 (DBN) or 1,8-diazabicyclo [5.4.0] undecene-7 (DBU), n-butyllithium, sec-butyllithium, t-butyllithium, potassium carbonate, sodium carbonate. It is desirable to use a base such as sodium hydride or potassium hydroxide as a reaction aid.

The reaction is usually carried out in the presence of a solvent, but the kind of the solvent is not particularly limited as long as the reaction has no side effect. Examples of the suitable solvent include hexane, benzene, toluene, methylene chloride, chloroform, diethyl ether, tetrahydrofuran, dioxane, acetone, methyl ethyl ketone, acetonitrile, ethyl acetate, N, N-dimethylformamide, dimethyl sulfoxide and the like. it can.

The amount of the carboxylic acid (III) or its reaction derivative used in the reaction is usually 1 to 10 equivalents, preferably 1 to 4 equivalents.

The reaction temperature is usually -100 ° C to 100 ° C.
C., preferably -78.degree. C. to 50.degree. C., and the time required for the reaction is usually 1 hour to 48 hours.

After completion of the reaction in each step, the desired compounds (I), (II), (IV) and (V) are isolated from the reaction mixture by a known method and, if necessary, column chromatography. It is purified by known means such as chromatography.

Next, the present invention will be described more specifically with reference to Examples and Reference Examples.

[0060]

【Example】

[0061]

Example 1 (Step D) N- (5-methyl-1,4-benzodioxane-6-carbo) -N-cyano-N′-t-butyl-N ′-(3
5-Dimethylbenzoyl) hydrazine 30.0 mg of N- (5-methyl-1,4-benzodioxane-6-carbo) -N-cyano-N'-t-butylhydrazine was dissolved in 3 ml of dry tetrahydrofuran and -72
At 00C, 0.100 ml of 1.59 M n-butyllithium hexane solution was added. After stirring at -72 ° C for 5 minutes, 36 mg of 3,5-dimethylbenzoyl chloride was added, and the temperature was -72 ° C.
The mixture was stirred at room temperature for 1 hour and at room temperature for 19 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The organic layer was washed with 5% aqueous sodium hydroxide solution, water and saturated brine, and dried over sodium sulfate. The solvent was evaporated, the residue was purified by thin layer silica gel chromatography, and the desired N- (5-methyl-1,4-benzodioxane-6-carbo) -N- was obtained.
20.7 mg of cyano-N'-t-butyl-N '-(3,5-dimethylbenzoyl) hydrazine was obtained (yield 47.4
%).

¹ H-NMR (CDCl ₃ ) δ (ppm): 1.69 (9H, s), 1.84
(3H, s), 2.31 (6H, s), 4.22-4.27 (4H, m), 6.10 (1H, d, J = 8.5H
z), 6.59 (1H, d, J = 8.5Hz), 7.08 (1H, s), 7.13 (2H, s)

[0063]

[Reference example]

[0064]

Reference Example 1 (Step A) N- (5-Methyl-1,4-benzodioxane-6-carbo) -N'-t-butyl-N'-formylhydrazine 1.00 g of N- (5-methyl- 10 ml of 1,4-benzodioxane-6-carbo) -N'-t-butylhydrazine
Was dissolved in 99% formic acid and 1.5 ml of acetic anhydride was added under water cooling. The reaction solution was stirred at room temperature for 5 days and concentrated. 70 ml of ethyl acetate was added to the concentrate, washed with saturated sodium bicarbonate solution, water and saturated saline, and dried with sodium sulfate. The solvent was distilled off to obtain 1.50 g of the desired N- (5-methyl-1,4-benzodioxane-6-carbo) -N'-t-butyl-N'-formylhydrazine (yield 94.9%). .

¹ H-NMR (CDCl ₃ ) δ (ppm): 1.46 (9H, s), 2.32
(3H, s), 4.24-4.32 (4H, m), 6.73 (1H, d, J = 8.4Hz), 7.09 (1H,
d, J = 8.4Hz), 7.29 (1H, s), 8.48 (1H, s)

[0066]

[Reference Example 2] (Step B) N- (5-methyl-1,4-dioxane-6-carbo)
-N-Cyano-N'-t-butyl-N'-formylhydrazine 0.85 g of N- (5-methyl-1,4-dioxane-6-
Carbo) -N'-t-butyl-N'-formylhydrazine was dissolved in 10 ml of dry N, N-dimethylformamide and 0.23 g of 60% sodium hydride was added under ice cooling. The reaction mixture was cooled with ice for 30 minutes and then at room temperature for 10 minutes.
After stirring for 1 minute, 0.65 g of 95% cyanogen bromide was added and stirred at room temperature for 80 minutes. The reaction mixture was poured into ice water and extracted with a mixed solvent of ethyl acetate and hexane (volume ratio 1: 1). The organic layer was washed with water and saturated saline and dried over sodium sulfate. The solvent was evaporated, the residue was purified by silica gel column chromatography, and the desired N- (5-methyl-1,4-dioxane-6-carbo) -N-cyano-N'-t-butyl-N 'was obtained. − 0.79 for formylhydrazine
g was obtained (yield 86%).

¹ H-NMR (CDCl ₃ ) δ (ppm): 1.57 (9H, s), 2.31
(3H, s), 4.27-4.33 (4H, m), 6.82 (1H, d, J = 8.4Hz), 7.16 (1H,
d, J = 8.4Hz), 8.56 (1H, s)

[0068]

Reference Example 3 (Step C) N- (5-methyl-1,4-benzodioxane-6-carbo) -N-cyano-N'-t-butylhydrazine 0.300 g of N- (5-methyl-1) , 4-Benzodioxane-6-carbo) -N-cyano-N'-t-butyl-
N'-formylhydrazine was added to 5 ml of 1,4-dioxane and 5 ml of 1N hydrochloric acid, and the mixture was heated under reflux for 2 hours. The reaction mixture was poured into an ice-cold aqueous solution of 10% sodium hydroxide and extracted with ethyl acetate. The organic layer was washed with water and saturated saline and dried over sodium sulfate. The solvent was evaporated, the residue was purified by silica gel chromatography, and the desired N- (5-methyl-1,4-benzodioxane-6-) was obtained.
Carbo) -N-cyano-N'-t-butylhydrazine
0.171 g was obtained (yield 62.5%).

¹ H-NMR (CDCl ₃ ) δ (ppm): 1.24
(9H, s), 2.28 (3H, s), 4.27-4.
33 (4H, m), 5.29 (1H, s), 6.81
(1H, d, J = 8.4 Hz), 7.09 (1H, d,
J = 8.4Hz)

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification code Internal reference number FI Technical indication location C07D 311/58 9360-4C 319/12 319/18 (72) Inventor Yoshihiro Sawada Yasu, Yasu-gun, Shiga Prefecture Machinosu 1041 Sankyo Stock Association In-house (72) Inventor Mikio Yanagi 4265-3 Kawataya, Okegawa City, Saitama Prefecture (72) Inventor Sugi ▲ Hiroyasu 2-6-11 Omori Nishi, Ota-ku, Tokyo (72) Inventor Tetsuya Toya 1090 Kamiochiai, Yono City, Saitama Nikkasha B-421

Claims (1)

[Claims] 1. A compound represented by the general formula (II): [Wherein R ¹ , R ² , R ³ , R ⁴ and R ⁵ are the same or different and each represents a hydrogen atom, halogen, cyano, hydroxy,
C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, C _1-6 alkoxy C _1-6 alkyl, C _1-6 alkoxy C _1-6 alkoxy, C _2-6 alkenyl, C _2-6 Alkynyl, carboxy, C _1-6 alkoxycarbonyl, C
_1-6 alkylcarbonyl, group -NR ⁷ R ^8, or a group -S
(O) _m R ⁷ (R ⁷ and R ⁸ are the same or different and represent a hydrogen atom, C _1-6 alkyl, phenyl) or
Alternatively, R ¹ and R ² , R ² and R ³ , R ³ and R ⁴ or R ⁴
And R ⁵ together form a group -A-CR ⁹ R ¹⁰ -CR ¹¹
R ¹² -B- or group -A-CR ⁹ R ¹⁰ -B- (A and B are the same or different and each represents an oxygen atom, a sulfur atom or methylene, and R ⁹ , R ¹⁰ , R ¹¹ and R ¹² are The same or different, each represents a hydrogen atom, halogen, C _1-4 alkyl, C _1-4 alkoxy), R ⁶ represents C _3-12 branched alkyl, X represents cyano, a group —SCCl ₃ , Group-SCCl ₂
F, group ^{_{-S (O) m NR 13 R}} 14, group -S (O) _m NR ¹³
CO ₂ R ¹⁴ , group —S (O) _m NR ¹³ COR ¹⁴ , group —S
(O) _m NR ¹³ SO ₂ R ¹⁴ , group -S (O) _m NR ¹³ CO
SR ¹⁴ , group -S (O) _m NR ¹³ SO ₂ N (R ¹⁴ ) ₂ , group A group —COCO ₂ R ¹³ , a group —CH ₂ OCOR ¹³ , or
The radical -CONR ¹³ R ¹⁴ (the above formulas, m represents 0, 1 or ^{2, R 1, R 2,} R 3, R 4, R 5 and R ⁶ have the same meanings as defined above, R ¹³ and R ¹⁴ is the same or different and is a hydrogen atom, C _1-6 alkyl, 1 to 3 C _1-4 alkyl or phenyl optionally substituted with halogen, benzyl, R ^{15 to} R ¹⁹ are R ¹ ~ Has the same meaning as R ⁵ )
Indicates. ] The compound represented by the following general formula (III): [Wherein R ¹⁵ , R ¹⁶ , R ¹⁷ , R ¹⁸ and R ¹⁹ have the same meanings as described above. ] The carboxylic acid represented by the formula or a reactive derivative thereof is reacted with the following general formula (I): [In the formula, R ^{1 to} R ⁶ , R ^{15 to} R ¹⁹ and X have the same meanings as described above. ] The manufacturing method of the dibenzoyl hydrazine derivative represented by these.