JPS58188858A - New pyrazole derivative - Google Patents

Abstract

NEW MATERIAL:A compound shown by the formula [R is (substituted) alkyl (benzoylmethyl and toluoyl methyl are omitted), substituted alkenyl, (substituted) aralkyl, acyl, carbamoyl, thiocarbonyl, sulfonyl, or sulfamoyl). EXAMPLE:1, 3-Dimethyl-4-(2, 4-dichloro-3-methylbenzoyl)-5-(p-bromophenacyloxy) pyrazole. USE:Having antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, etc., useful as various kinds of physiologically active substances, and expected as industrial germicide, etc. PROCESS:1,3-Dimethyl-4-(2,4-dichloro-3-methylbenzoyl)-5-hydroxypyrazole or its alkaline(earth)metal salt, or quaternary ammonium salt is reacted with an organic halide shown by the formula (X is F, Cl, Br or I) in an inert solvent in the presence or absence of an acid binder, to give a compound shown by the formula I .

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to novel pyrazole derivatives. More specifically, in the general formula (1), R is an alkyl group that may have a substituent (however,
(excluding benzoylmethyl group and toluoylmethyl group),
Indicates an alkenyl group having a substituent, an aralkyl group which may have a substituent, an acyl group, a carbamoyl group, a thiolcarbonyl group, a sulfonyl group, or a sulfamoyl group]
This invention relates to a novel pyrazole derivative represented by:

While researching the physiological activities of a series of pyrazole derivatives, the present inventors examined 1,3-dimethyl-a-(2゜4-cyclo-3-methylbenzoyl)-5-hydroxypyrazole derivatives, and found that the general formula It has been found that the compound represented by (1) has antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, etc. Therefore, the compound of the present invention is expected to be used as an industrial fungicide, but the compound is also useful as a starting material for various physiologically active substances.

In the above general formula (1) Ic, the alkyl groups C1 to C1! methyl, ethyl, n-propyl, t-propyl, n-7fl, 5ec-7'thyl, tert-butyl, i-butyl, n-pentyl, i-
Examples include pentyl, n-hexyl, n-hebutyl, n-octyl, n-decyl, and n-dodecyl.

The alkyl group of the alkyl group having a substituent is cl to C!
and its substituents include halogen atoms such as chloro and bromine, nitrile groups, C1-4 alkoxycarbonyl groups, carbamoyl groups, tti-CO-R''(R''
tl-Cx~6 alkyl group, styryl group, chenyl group, halogen-substituted chenyl group, hisricyl group, phenyl group or one or more C1~4 alkyl group... rogene atom, nitro group or 01~4 group Represents a phenyl group substituted with an alkoxy group. ) is an acyl group represented by

Specific examples include chloromethyl, bromomethyl, cyanomethyl, methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, butoxycarbonylmethyl, acetylmethyl, t-butylcarbonylmethyl, 2-methylpiperidine-1-carbonylmethyl, and 5-chloromethyl. -2-f enylcarbonylmethyl, bi,
, 3luponylmethyl, 2-chloroethyl, 2-cyanoethyl, 1-methoxycarbonylethyl, l-ethoxycarbonylethyl 1.1-butoxycarbonylethyl,
3.4-cyztylphenacyl, p-ethylphenacyl, p-n-propylphenacyl, p-n 7 butylphenacyl, p-i-butylphenacyl, P L-butylphenacyl, 0-chlorophenacil, p-chlorophenacil p-bromophenacyl, 2,4-dichlorophenacyl, 2-chloro-4-nitrophenacyl, p-
Examples include nitrophenacyl, 0-methoxyphenacyl, m-methoxyphenacyl, p-methoxyphenacyl, 2,4-dichloro-3-methylphenacyl, and cinnamoylmethyl.

The alkenyl group of the alkenyl group having a substituent is C1-4
and the substituent is a halogen atom, an alkoxycarbonyl group of 01 to 4, or a phenyl group, and specific examples thereof include 4-chloro-2-butenyl, 3-metho*dicarbonyl-2-7'lovenyl, 3-ethoxy carbonyl-2
-propenyl, t*&t3-phenyl-2-propenyl groups, and the like.

The aralkyl group of the aralkyl group which may have a substituent is C7~! The substituent is an alkyl group, a hydroxyl group, a halogen atom, a nitro group or a cyan group of Cx~4. Specific examples include benzyl, phenethyl, phenylpropyl, α, α-dimethylbenzyl, p-methylbenzyl, p-10 lobenzyl, 2,4-dichlorobenzyl, m-nitrobenzyl, p-nitrobenzyl, 2-chloro- 4-nitrobenzyl, p-cyanobenzyl, p-
Examples thereof include hydroxybenzyl, 3.5-di-t-butyl-4-hydroxybenzyl, and the like.

The acyl group is represented by -Co-R1, R"FiCx
Represents a phenyl group substituted with a ~6 alkyl group, a C7-9 aralkyl group, a phenyl group, or one or more halogen atoms, a C1-4 alkyl group, a C1-4 alkoxy group, or a hanitro group . Specific examples of acyl groups include acetyl, propionyl, chloroacetyl, bromoacetyl, trifluoroacetyl, 0-methylbenzoyl, m-
Methylbenzoyl, p-methylbenzoyl, p t-propylbenzoyl, p-methoxybenzoyl, 3,4-
Dimethoxybenzoyl, 0-chlorobenzoyl, p-chlorobenzoyl, p-bromobenzoyl, p-nitropenzoyl, 2,4-dichlorobenzoyl, 2-chlorobenzoyl
Examples include 4-nitrobenzoyl, 2,4-cyclo-3-methylbenzoyl, and the like.

Carbamoyl group is represented by -CON'R3\R4, and RM, R4-Ct-4 alkyl group 01-4 alkoxy group, phenyl group or tiR3 and R4 are bonded, and C2-8 including N is bonded. Represents a ring. Specific examples include N,
N-dimethylcarbamoyl, NIN-diethylcarbamoyl, N-methyl-N-methoxycarbamoyl, N,
N-tetramethylenecarbamoyl, N,N-hentamethylenecarbamoyl, N,N-hexamethylenecarbamoyl, N-)ethyl-N-phenylcarbamoyl, N
-ethyl-N-phenylcarbamoyl, or 3.5-
Examples include dimethyl-pyrazolylcarbonyl.

Thiol carbonyl group is represented by 1008-R5
Specific examples of R5-01-4 alkyl groups, halogen-substituted benzyl groups, or C7-1o aralkyl groups include FiS-methylcarbonyl, S-ethylcarbonyl, S-benzylcarbonyl, 5-(p- Examples include chlorobenzyl)carbonyl, S-(α,α-dimethylbenzyl)carbonyl, and the like.

Sulfonyl group is represented by 8Ox-R', R6 is 0
Extracted by the alkyl group of numbers 1 to 1, the aryl group of C6 to 1e,
Specific examples of ``s'' include methanesulfonyl, ethanesulfonyl, benzenesulfonyl, toluenesulfonyl, and the like.

, R7 sulfamoyl group and u-8o! Represented by N＼R
8 Re represents an alkyl group or phenyl group of R7 and R''dC1-4. Specific examples thereof include N,N-dimethylsulfonyl, N,N-diethylsulfonyl, N-
Examples include phenylsulfonyl, N-methyl-N-phenylsulfonyl, and the like.

Representative examples of the compound of the present invention represented by general formula (1) are shown below.

H3 The compound of the present invention represented by the general formula <1) is l,3-dimethyl-4-(2,4-dichloro-3-methylbenzoyl)-5-hydroxypyrazole or its a. Alkaline metal salt, alkaline earth metal salt, tertiary ammonium salt, general formula (■) R-X (n) [wherein R has the same meaning as general formula (1), and fluorine, chlorine, bromine and iodine] in a solvent inert to the reaction in the presence or absence of an acid binder.

When using 1.3-dimethyl-4-(2,4-dichloro-3-methylbenzoyl)-5-hydroxypyrazole as a raw material, alkali metal carbonates such as sodium carbonate and potassium carbonate, tertiary metal carbonates such as triethylamine, etc. Amines are used as acid binders.

Also, 1,3-dimethyl-4-('2,4-dichloro3
When an alkali metal salt, alkaline earth metal salt, tertiary ammonium salt, etc. of -methylbenzoyl)-5-hydroxypyrazole is used as a raw material, it is subjected to the reaction without adding the above-mentioned acid binder.

Examples of alkali metal salts include sodium salts and potassium salts, alkaline earth metal salts include calcium salts, and tertiary ammonium salts include triethylammonium salts and tri-n-butylammonium salts.

As the solvent for the reaction, any solvent that is inert to the reaction can be used, such as aromatic hydrocarbons such as benzene, toluene, and xylene; In addition to halogenated hydrocarbons, ethers such as ethyl ether, tetrahydrofuran, and dioxane, and ketones such as acetone and methyl ethyl ketone, acetonitrile, N,N-dimethylformamide, and dimethyl sulfoxide are used. The reaction temperature can be carried out at a temperature ranging from room temperature to 150°C, preferably at a temperature ranging from 50°C to 100°C.

The reaction time varies depending on the raw materials used, the reaction temperature, and the type of solvent, and is not necessarily constant, but is usually in the range of 0.5 to 10 hours. The amount of acid binder is typically 1,3-dimethyl-4-(2,4-dichloro-3-methylbenzoyl)
The amount is in the range of 1 to 2 times mole relative to -5-hydroxypyrazole. The amount of organic halide represented by general formula (11) is l,3-di)thyl-4-(2,4-cyclo-3-
It can be carried out in an amount of 0.5 to 5 times the molar amount of methylbenzoyl)-5-hydroxypyrazole, but it is usually in the range of 1 to 2 times the molar amount.

As the organic compound represented by the general formula (1) used in the present invention, methyl bromide, methyl iodide, ethyl bromide, ethyl iodide, n-propyl bromide, n-butyl bromide, hexyl chloride, chloride Dotesyl, chloroacetonitrile, 1-bromo-2-chloroethane, ethyl bromoacetate, methyl α-chloro-propionate, chloroacetone, bromomethyl-3-pyridylketone, 3-ethoxycarbonylallyl bromide, 3-phenyl-1-chloropropane, p-chlorobenzyl chloride, 3.4-dimethylphenacyl bromide, p-methoxyphenacyl bromide, acetyl chloride, phenylacetic acid chloride, benzoyl chloride, 2.4-dichlorobenzoyl chloride, N, N
-dimethylcarbamoyl chloride, S-ethyl chloroformate, benzenesulfonyl chloride, N, N
-dimethylsulfonyl chloride and the like can be exemplified.

The compound of the present invention can be obtained as a crude product by distilling off the solvent after completion of the reaction, but it can also be obtained with high purity by using conventional purification methods such as recrystallization and column chromatography.

Next, manufacturing examples of the present invention will be specifically explained.

Example 1.3-dimethyl-4-(2,4-dichloro-3-methylbenzoyl)-5-hydroxypyrazole 2,99
F (0.01 mol), anhydrous potassium carbonate 2.1y (
After suspending 2.78 f (0.01 mol) of p-bromophenacyl bromide in 20-methyl ethyl ketone for 30 minutes, It was dripped. After the dropwise addition, the reaction was carried out under reflux for 3 hours, and after cooling, the inorganic substances were removed and the solvent was distilled off under reduced pressure to obtain a crude product of 4.52. Purified by column chromatography using chloroform, 3.79
1,3-dimethyl-4-(2,4-cyclo-3-methylpensoyl)-s-(p-bromophenacyloxy)pyrazole was obtained. Melting point of this #i127.0~
The temperature was 128.5°C. (Yield 74.6 mol)

Claims (1)

[Claims] General formula (1) [In the formula, R is an alkyl group that may have a substituent (provided that
(excluding benzoylmethyl group and toluoylmethyl group),
Indicates an alkenyl group having a substituent, an aralkyl group which may have a substituent, an acyl group, a carbamoyl group, a thiolcarbonyl group, a sulfonyl group, or a sulfamoyl group]
A new pyrazole derivative represented by