JPS6330899B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to novel pyrazole acetic acids and a method for producing the same. More specifically, the present invention relates to the general formula () The present invention relates to pyrazole acetic acids represented by the formula and a method for producing the same. However, in the above general formula (), R ¹ is a hydrogen atom; a lower alkyl group such as a methyl group, an ethyl group, a propyl group, a butyl group; a phenyl group that may have a substituent; a naphthyl group; a pyridyl group; Represents a pyrimidinyl group that may be substituted with a lower alkyl group such as a methyl group, ethyl group, propyl group, butyl group, and the substituent is a halogen atom such as a fluorine atom, chlorine atom, bromine atom, or iodine atom; methyl , a lower alkyl group such as an ethyl group, a propyl group, a butyl group; a lower alkoxy group such as a methoxy group, an ethoxy group, a propoxy group, a butoxy group; or a nitro group. base
CH ₂ CO ₂ R ² is located at the 3rd or 5th position of the pyrazole ring. Here, R ² is a hydrogen atom; an alkyl group such as a methyl group, ethyl group, propyl group, butyl group;
vinyl group, allyl group, prenyl group, geranyl group,
It represents an alkenyl group such as a farnesyl group; or an alkynyl group such as a propargyl group. The pyrazole acetic acids represented by the general formula () provided by the present invention have excellent antibacterial activity against rice blast disease, and many of the compounds are effective against rice blast rot, mongale disease, and cucumber root rot. It exhibits high antibacterial activity against one or more of various plant pathogenic fungi such as powdery mildew, tangy mildew, gray mold, downy mildew, gray mold of kidney beans, and kinkweed, and has no phytotoxicity to agricultural crops. It is useful as a fungicide for agriculture and horticulture. Representative compounds of pyrazole acetic acids represented by the general formula () are listed below.

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[Table] According to the present invention, pyrazole acetic acids represented by the general formula () can be produced by the following method. That is, the general formula () (In the formula, R ³ and R ⁴ are the same or different and each represents a lower alkyl group.)
or general formula () (In the formula, R ³ and R ⁴ are the same or different and each represents a lower alkyl group.) and the general formula () R ¹ NHNH ₂ ... () [In the formula, R ¹ is the same as in the general formula ()] have the same meaning. ] When reacting with the hydrazine compound shown in the presence of an acid, the general formula (') is obtained. [In the formula, R ¹ has the same meaning as in the general formula (); -CH ₂ CO ₂ R ³ group is located at the 3rd or 5th position of the pyrazole ring, and R ³ has the same meaning as in the general formula () have meaning. ] A pyrazole acetic acid ester represented by the general formula () is obtained, and if necessary, this is hydrolyzed or converted into an ester to obtain a pyrazole acetic acid represented by the general formula (2). The above method will be explained in detail below. First, by reacting a compound represented by the general formula () and/or a compound represented by the general formula () with a hydrazine compound represented by the general formula () in the presence of an acid, a compound represented by the general formula ('a) is obtained. [In the formula, R ¹ and R ³ have the same meanings as in the general formula ('). ] Pyrazole-3
-yl acetate esters and/or general formula ('b) [In the formula, R ¹ and R ³ have the same meanings as in the general formula ('). ] Pyrazole-5
-ylacetic acid esters are obtained. Acids include hydrochloric acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, oxalic acid, benzoic acid,
Inorganic or organic acids such as p-toluenesulfonic acid are used. This reaction usually involves alcohols such as methanol and ethanol, ethers such as tetrahydrofuran and 1,2-dimethoxyethane, aromatic hydrocarbons such as benzene, toluene, and xylene, N,N-dimethylformamide, dimethyl sulfoxide, etc. The reaction is carried out in the presence or absence of a solvent inert to the reaction at a temperature range of room temperature to 150°C, preferably 50°C to 100°C. In addition, when carrying out this reaction in the presence of acetic acid, acetic acid is used in excess of the compound represented by the general formula () or the compound represented by the general formula () as a raw material, so that the acetic acid acts as a solvent. It may also serve as a role. The pyrazol-3-yl acetate represented by the general formula ('a) or the pyrazol-5-yl acetate represented by the general formula ('b) obtained by the above reaction can be prepared, for example, by the following method (i). ) to (iii) are easily hydrolyzed or esterified. [In the formula, R ¹ and R ³ have the same meanings as in the general formula ('). ] [In the formula, R ¹ has the same meaning as in the general formula (), R ⁵ represents an alkyl group, an alkenyl group, or an alkynyl group, and X represents a halogen atom. ] [In the formula, R ¹ and R ³ have the same meanings as in general formula ('), and R ⁵ represents an alkyl group, an alkenyl group, or an alkynyl group. In other words, method (i) involves adding a pyrazol-3-yl acetate represented by the general formula ('a) or a pyrazol-5-yl acetate represented by the general formula ('b) to water according to a conventional method. Hydrolysis is carried out in the presence of an alkali such as potassium oxide or sodium hydroxide. Method (ii) is a pyrazol-3-yl acetic acid represented by general formula (a-1) or general formula (b-1) obtained by method (i).
The pyrazol-5-yl acetic acids represented by are first treated with a thionyl halide such as thionyl chloride or thionyl bromide in an inert solvent such as benzene or toluene by a conventional method to obtain the corresponding acid halide; The acid halide has the general formula R ⁵ OH
The alcohol represented by is mixed with benzene in the presence of a tertiary amine such as pyridine or triethylamine.
The reaction is carried out in an inert solvent such as toluene at room temperature. Method (iii) is to add a pyrazol-3-yl acetate represented by the general formula ('a) or a pyrazol-5-yl acetate represented by the general formula ('b) to an inorganic compound such as benzene or toluene according to a conventional method. This is carried out by heating and stirring together with an alcohol represented by the general formula R ⁵ OH in an active solvent in the presence of an alkali such as potassium hydroxide or sodium hydroxide, and distilling off the produced low-boiling alcohol. The target pyrazole acetic acid is pyrazole-3
When obtained as a mixture of pyrazole-5-ylacetic acids and pyrazole-5-ylacetic acids, it is easy to obtain the desired pyrazole acetic acid by subjecting this mixture to conventional separation means such as recrystallization, distillation, and chromatography. can be obtained. The compound represented by the general formula () used in the present invention can be obtained by reacting 1-lower alkoxy-1-buten-3-yne and di-lower alkyl carbonate in a lower alkanol in the presence of sodium alcoholate. The compound represented by the general formula () can be obtained by reacting 1-lower alkoxy-1-buten-3-yne and di-lower alkyl carbonate in the presence of sodium alcoholate [Ber., 89 , 878 (1956)].
Hydrazine compounds represented by the general formula () include hydrazine, methylhydrazine, phenylhydrazine, 4-chlorophenylhydrazine, 2,4-
Examples include dichlorophenylhydrazine, 4-methylphenylhydrazine, 4-methoxyphenylhydrazine, 4-nitrophenylhydrazine, β-naphthylhydrazine, 2-pyridylhydrazine, and 3-methylpyrimidinylhydrazine. EXAMPLES The present invention will be explained below with reference to Examples, but the present invention is not limited in any way by these Examples. Example 1 Synthesis of ethyl 1-phenylpyrazol-3-ylacetate and ethyl 1-phenylpyrazol-5-ylacetate 0.5 g of ethyl 3,5,5-triethoxy-2-pentenoate and phenylhydrazine hydrochloride
0.27 g was added to 10 ml of ethanol and heated under reflux for 30 minutes. Water was added to the resulting reaction solution, and then this solution was extracted with diethyl ether. The ether extract was subjected to silica gel thin layer chromatography (solvent:
By separating and purifying with chloroform), the following can be obtained.
Oily ethyl 1-phenylpyrazol-3-ylacetate (compound 2) each with an NMR spectrum
0.13g and oily 1-phenylpyrazole-5
-0.22g of ethyl acetate (compound 1) was obtained. NMR spectrum (CDCl ₃ ) δ: Compound 1 1.04 (3H, t, J = 7Hz), 3.53
(2H, s), 3.93 (2H, q, J = 7Hz), 6.20 (1H, d, J = 2Hz), 7.22 (5H,
s), 7.43 (1H, d, J = 2Hz) Compound 2 1.16 (3H, t, J = 7Hz), 3.61
(2H, s), 4.04 (2H, q, J = 7Hz), 6.28 (1H, d, J = 2Hz), 7.3 (5H,
m), 7.66 (1H, d, J = 2Hz) 1-(3-methylpyrimidinyl)pyrazole- having the following properties was prepared in the same manner as in Example 1.
Ethyl 5-ylacetate (Compound 13), ethyl 1-(3-methylpyrimidinyl)pyrazol-3-ylacetate (Compound 14), ethyl 1-methylpyrazol-5-ylacetate (Compound 15) and 1-methylpyrazole- Ethyl 3-yl acetate (compound 16) was obtained.

[Table] Example 2 Synthesis of ethyl 1-phenylpyrazol-3-yl acetate and ethyl 1-phenylpyrazol-5-yl acetate 0.5 g of ethyl 3,5-diethoxy-2,4-pentadienoate and enylhydrazine hydrochloride
0.4 g was added to 10 ml of ethanol and heated under reflux for 20 hours. Water was added to the resulting reaction solution, and then this solution was extracted with ethyl acetate. The ethyl acetate extract was dried over anhydrous magnesium sulfate, and the solvent was distilled off.
The residue was separated and purified by silica gel chromatography (solvent: benzene-chloroform) to obtain 0.14 g of 1-phenylpyrazol-3-yl ethyl acetate (compound 2) and 1-phenylpyrazol-5-yl ethyl acetate. (Compound 1)
Obtained 0.37g. Example 3 Synthesis of ethyl pyrazol-3-ylacetate Ethyl 3,5,5-triethoxy-2-pentenoate and ethyl 3,5-diethoxy-2,4
- a mixture of pentadienoates in a weight ratio of 3:1 50
g and 18 g of hydrazine hydrate in 200 ml of ethanol.
In addition, 50 ml of concentrated hydrochloric acid was added dropwise to this solution, and then
The mixture was heated under reflux for 14 hours. After distilling off the solvent from the resulting reaction solution, water was added to the residue, and an aqueous potassium carbonate solution was further added to make it slightly alkaline, and this solution was extracted with ethyl acetate. The ethyl acetate extract was dried over anhydrous sodium sulfate, the solvent was distilled off, and the residue was purified by silica gel chromatography (solvent: benzene-ethyl acetate) to obtain the following.
Oily pyrazole-3 with NMR spectrum
17 g of ethyl -ylacetate (compound 11) was obtained. NMR spectrum (CDCl ₃ ) δ: 1.23 (3H, t, J = 7Hz), 3.76 (2H,
s), 4.15 (2H, q, J=7Hz), 6.24 (1H,
d, J = 2Hz), 7.52 (1H, d, J = 2Hz) 1-(4-nitrophenyl)pyrazole-5- having the following properties was prepared in the same manner as in Example 3.
Ethyl ylacetate (Compound 3), ethyl 1-(4-nitrophenyl)pyrazol-3-ylacetate (Compound 4), ethyl 1-(3,4-dichlorophenyl)pyrazol-5-ylacetate (Compound 5) and 1-
(3,4-dichlorophenyl)pyrazole-3-
Ethyl yl acetate (compound 6) was obtained.

[Table] Example 4 Synthesis of 1-phenylpyrazol-5-ylacetic acid 3 g of ethyl 1-phenylpyrazol-5-ylacetate (compound 1) and 1 g of sodium hydroxide were added to a mixed solution of 50 ml of ethanol and 5 ml of water. and stirred at room temperature overnight. 100 ml of water was added to the resulting reaction solution, and then this solution was washed with diethyl ether. Dilute hydrochloric acid was added to the aqueous layer to make it acidic, and this solution was extracted with chloroform. After distilling off the solvent from the chloroform extract, the residue was recrystallized with a benzene-n-hexane mixed solution to obtain 2.3 g of 1-phenylpyrazol-5-yl acetic acid (compound 7) having the following properties. . Compound 7 mp.105-106℃ NMR (acetone-d6) δ: 3.72 (2H,
s), 6.31 (1H, d, J = 2Hz), 7.46 (5H, s), 7.51 (1H, d, J = 2Hz) 1-Phenylpyrazole- having the following properties was prepared in the same manner as in Example 4. 3-yl acetic acid (compound 8), 1-(3,4-dichlorophenyl)pyrazol-5-yl acetic acid (compound 9) and 1-(3-
Methylpyrimidinyl)pyrazol-3-yl acetic acid (compound 10) was obtained. Compound 8 mp.73-75℃ NMR (acetone-d6) δ: 3.60 (2H,
s), 6.35 (1H, d, J = 2Hz), 7.2 (3H, m), 7.66 (2H, m), 8.05 (1H, d, J = 2Hz) Compound 9 mp.156℃ NMR (acetone-d6) δ: 3.76 (2H,
s), 6.34 (1H, d, J = 2Hz), 7.5 (3H, m), 7.65 (1H, d, J = 2Hz) Compound 10 mp.169-170℃ NMR (DMSO-d6) δ: 2.41 (3H ,s,)
3.60 (2H, s), 6.41 (1H, d, J = 2Hz), 7.19 (1H, d, J = 5Hz), 8.44 (1H, d, J = 2Hz), Example 5 Pyrazol-3-ylgeranyl acetate Synthesis of ethyl pyrazol-3-yl acetate (compound 11)
23g, geraniol 66g and potassium hydroxide 0.2
g was added to 300 ml of toluene, and heating and stirring were continued while the produced ethanol was distilled off together with the toluene. After 1 hour, add potassium hydroxide to the reaction solution.
0.2 g was added, and heating and stirring were continued for 2 hours. The temperature of the reaction solution obtained by cooling was brought to room temperature, and 300 ml of diethyl ether was added to the reaction solution, followed by washing with water.
After concentrating the organic layer and distilling off geraniol, the residue was separated and purified using silica gel chromatography (solvent: benzene) to obtain an oily pyrazol-3-ylgeranyl acetate (compound 12) having the following NMR spectrum. ) was obtained. NMR spectrum (CDCl ₃ ) δ: 1.55 (3H, s), 1.62 (6H, s), 2.0 (4H, m), 3.70 (2H, s), 4.59 (2H, d, J=7Hz), 5.03 (1H , m), 5.30 (1H, t, J = 7Hz), 6.19 (1H, d, J = 2Hz), 7.47 (1H, d, J =
2Hz).

Claims (1)

[Claims] 1 General formula () (In the formula, R ¹ represents a hydrogen atom, a lower alkyl group, a phenyl group that may have a substituent, a naphthyl group, a pyridyl group, or a pyrimidinyl group that may be substituted with a lower alkyl group, and the substituent means a halogen atom, a lower alkyl group, a lower alkoxy group, or a nitro group; -CH ₂ CO ₂ R ² group is located at the 3rd or 5th position of the pyrazole ring, and R ² is a hydrogen atom, an alkyl group, an alkenyl group or represents an alkynyl group.) Pyrazole acetic acids represented by: 2 General formula () Compound and/or general formula () represented by By reacting the compound represented by the general formula () with the hydrazine compound represented by the general formula () R ¹ NHNH ₂ ...() in the presence of an acid, the general formula (') is obtained. A general formula () characterized by obtaining a pyrazole acetic acid represented by and optionally hydrolyzing or converting it into an ester A method for producing pyrazole acetic acids represented by (In the above formula, R ¹ is a hydrogen atom, a lower alkyl group,
Represents a phenyl group, naphthyl group, pyridyl group, or pyrimidinyl group optionally substituted with a lower alkyl group, which may have a substituent, and the substituent is a halogen atom, a lower alkyl group, a lower alkoxy group, or a nitro group. -CH ₂ CO ₂ R ² group is located at the 3rd or 5th position of the pyrazole ring, R ² represents a hydrogen atom, an alkyl group, an alkenyl group or an alkynyl group; -CH ₂ CO ₂ R ³ group is located at the 3rd or 5th position of the pyrazole ring; R ³ and R ⁴ are the same or different and each represents a lower alkyl group. )