JP2000226375A - Production of pyridazin-3-one derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an industrially advantageous method for producing a pyridazin-3-one derivative having excellent herbicidal activity. SOLUTION: A hydrazone compound of general formula I (X is H or a halogen; Y is a halogen; W is H or ZR1; Z is oxygen or sulfur; R1 is H, an alkyl or the like) is reacted with a malonic acid derivative of general formula II of R2CH(COOH)2 (R2 is H or an alkyl) in the presence of 2-methyl-5- ethylpyridine to give a carboxylic acid derivative of general formula III (X, Y, W and R2 are each as shown above) or its salt, which is reacted with an acid to give a pyridazin-3-one derivative of formula IV.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a pyridazine-3-
The present invention relates to a method for producing an on derivative.

[0002]

For example, equation (5) Have excellent herbicidal activity, and it has been desired to develop an industrially advantageous method for producing these pyridazin-3-one derivatives. Conventionally, a carboxylic acid derivative represented by the following general formula (3) or a salt thereof has been isolated, and therefore, operations such as extraction and concentration have been required, and accompanying equipment for dust control has been required.

[0003]

Means for Solving the Problems The present inventors have been keen to develop a method which can be industrially advantageously produced when producing a pyridazin-3-one derivative represented by the following general formula (4). As a result of repeated studies, the present invention has been reached. That is, the present invention provides a compound represented by the general formula (1): (Wherein, X represents a hydrogen atom or a halogen atom, Y represents a halogen atom, W is a hydrogen atom or a ZR ^1,, Z represents an oxygen atom or a sulfur atom, R ¹ represents a hydrogen atom, C1- C6 alkyl group, C1-C6 haloalkyl group, C
3-C8 cycloalkyl group, benzyl group, C3-C6 alkenyl group, C3-C6 haloalkenyl group, C3-C6 alkynyl group, C3-C6 haloalkynyl group, cyano C1-C6 alkyl group, C2-C8 (alkoxyalkyl) Group, C2-C8
(Alkylthioalkyl) group, carboxy C1-C6 alkyl group, (C1-C8 alkoxy) carbonyl C1-C6 alkyl group, {(C1-C4 alkoxy) C1-C4 alkoxy} carbonyl C1-C6 alkyl group, (C3-C8 cycloalkyl Alkoxy) carbonyl C1-C6 alkyl group, or
{(C1-C6 alkoxy) carbonyl C1-C6 alkyl} represents an oxycarbonyl C1-C6 alkyl group. ) And a malonic acid derivative represented by the general formula (2) R ² CH (COOH) ₂ (wherein R ² represents a hydrogen atom or a C1-C3 alkyl group), −
Reacting in the presence of 5-ethylpyridine to obtain a compound of the general formula (3) (Wherein, X, Y, W and R ² have the same meanings as described above), and then reacting with a carboxylic acid derivative represented by the formula (4) (Wherein, X, Y, W and R ² have the same meanings as described above).

[0004]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail. In the compound of the present invention, examples of the halogen atom represented by X and Y include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. C1 represented by R ¹
-C6 alkyl groups include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, t
-Butyl group, amyl group, isoamyl group, t-amyl group and the like.
Chloroethyl group, 2-bromoethyl group, 2,2,2-trifluoroethyl group and the like; C3-C8 cycloalkyl group includes cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group and the like; As the -C6 alkenyl group, an allyl group, 1-
Methyl-2-propenyl group, 3-butenyl group, 2-butenyl group, 3-methyl-2-butenyl group, 2-methyl-3
-Butenyl group and the like, and examples of the C3-C6 haloalkenyl group include a 2-chloro-2-propenyl group and a 3,3-
Dichloro-2-propenyl group and the like, and C3-C6
Examples of the alkynyl group include a propargyl group, 1-methyl-
A 2-propynyl group, a 2-butynyl group, a 1,1-dimethyl-2-propynyl group and the like; a C3-C6 haloalkynyl group includes a 3-bromopropargyl group; a cyano C1-C6 alkyl group; As a (C2-C8 alkoxyalkyl) group, a methoxymethyl group, a methoxyethyl group, an ethoxymethyl group, an ethoxyethyl group, and the like; and as a (C2-C8 alkylthioalkyl) group, Is
A methylthiomethyl group, a methylthioethyl group and the like can be mentioned, and as the carboxy C1-C6 alkyl group, a carboxymethyl group, a 1-carboxyethyl group, a 2-carboxyethyl group and the like can be mentioned, and (C1-C8 alkoxy) carbonyl C1- Examples of the C6 alkyl group include a methoxycarbonylmethyl group, an ethoxycarbonylmethyl group, a propoxycarbonylmethyl group, an isopropoxycarbonylmethyl group, a butoxycarbonylmethyl group, an isobutoxycarbonylmethyl group, a t-butoxycarbonylmethyl group,
Amyloxycarbonylmethyl group, isoamyloxycarbonylmethyl group, t-amyloxycarbonylmethyl group, 1-methoxycarbonylethyl group, 1-ethoxycarbonylethyl group, 1-propoxycarbonylethyl group, 1-isopropoxycarbonylethyl group, 1 -Butoxycarbonylethyl group, 1-isobutoxycarbonylethyl group, 1-t-butoxycarbonylethyl group, 1-
Amyloxycarbonylethyl group, 1-isoamyloxycarbonylethyl group, 1-t-butoxycarbonylethyl group, 1-amyloxycarbonylethyl group, 1-isoamyloxycarbonylethyl group, 1-t-amyloxycarbonylethyl group and the like. ｛(C1-C4
Alkoxy) C1-C4 alkoxy @ carbonyl C1-
Examples of the C6 alkyl group include a methoxymethoxycarbonylmethyl group, a methoxyethoxycarbonylmethyl group,
A methoxyethoxycarbonylethyl group and the like;
(C3-C8 cycloalkoxy) carbonyl C1-C6
Examples of the alkyl group include a cyclobutyloxycarbonylmethyl group, a cyclopentyloxycarbonylmethyl group, a cyclohexyloxycarbonylmethyl group, a 1-cyclobutyloxycarbonylethyl group, a 1-cyclopentyloxycarbonylethyl group, a 1-cyclohexyloxycarbonylethyl group, and the like. Examples of the {(C1-C6 alkoxy) carbonyl C1-C6 alkyl} oxycarbonyl C1-C6 alkyl group include a (methoxycarbonyl) methoxycarbonylmethyl group and a (ethoxycarbonyl) methoxycarbonylmethyl group.

[0005] Examples of the C1-C3 alkyl group represented by R ² include a methyl group, an ethyl group and a propyl group.

Next, a method for producing the compound of the present invention will be described. The pyridazin-3-one derivative represented by the general formula (4) is obtained by converting a hydrazone compound represented by the general formula (1) and a malonic acid derivative represented by the general formula (2) into 2-methyl-5-ethylpyridine. A step of obtaining a carboxylic acid derivative represented by the general formula (3)
), And after the completion of Step 1, an acid is added, followed by a step of performing a reaction (referred to as Step 2).

The range of the reaction temperature in step 1 is usually 70 to 2
It is about 00 ° C, preferably about 70-100 ° C. The range of the reaction time is usually about 5 to 48 hours. The amount of the reagent used for the reaction is such that the malonic acid derivative represented by the general formula (2) is about 1 to 10 mol per mol of the hydrazone compound represented by the general formula (1),
Methyl-5-ethylpyridine is usually about 1 to 10 mol,
It is preferably about 1 to 3 mol. Usually, a solvent is used in the reaction, and examples of such a solvent include C7 to C15 aliphatic hydrocarbons such as heptane and octane, and aromatic hydrocarbons such as benzene, toluene and chlorobenzene, and mixtures thereof. C7 such as octane
-C15 aliphatic hydrocarbons are preferred.

The range of the reaction temperature in step 2 is usually from 70 to 2
It is about 00 ° C, preferably about 90 to 140 ° C. In the reaction, it is preferable to carry out the reaction while removing water from the reaction system, such as by using a drying agent such as azeotropic dehydration or molecular sieve. The range of the reaction time is usually about 5 to 48 hours.

The acids used in the reaction include fatty acids such as acetic acid, propionic acid, trimethylacetic acid, chloroacetic acid, trifluoroacetic acid, phenylacetic acid, butyric acid, isobutyric acid, valeric acid and isovaleric acid, benzoic acid, Nitrobenzoic acid, 4
Organic acids such as benzoic acids such as -chlorobenzoic acid, 3,5-dinitrobenzoic acid, and 4-methoxybenzoic acid; and sulfonic acids such as p-toluenesulfonic acid, benzenesulfonic acid, methanesulfonic acid, and trifluoromethanesulfonic acid. And inorganic acids such as sulfuric acid, hydrochloric acid and phosphoric acid, and acidic cation exchange resins such as Amberlite CG-50 and Amberlite IR-120.

The amount of the acid used in the reaction is usually 1 to 1 with respect to 1 mol of the hydrazone compound represented by the general formula (1).
It is about 0 mol, preferably about 1 to 3 mol.
Usually, a solvent is used for the reaction.
The same solvent as in Step 1 is used. It is also possible to add calcium carbonate into the reaction system.

After completion of the reaction, the reaction mixture is filtered to remove molecular sieves, calcium carbonate, and the like, if added. (1) The reaction mixture is concentrated as it is. (2) The reaction solution is poured into an aqueous solution of a mineral acid such as hydrochloric acid or dilute sulfuric acid, and the mixture is extracted with an organic solvent under acidic conditions, and then the organic layer is dried and concentrated. After purification, if necessary, by recrystallization, column chromatography or the like, the pyridazin-3-one derivative represented by the general formula (4) can be produced.

As the malonic acid derivative represented by the general formula (2) used in the above production method, a commercially available one can be used, or it can be produced according to a known method. Further, the hydrazone compound represented by the general formula (1) can be obtained by converting the hydrazone compound represented by the general formula (5) (Wherein V represents an iodine atom, a bromine atom or a chlorine atom), or a dihalotrifluoroacetone derivative represented by the general formula (6): (Wherein V represents the same meaning as described above) by reacting a dihalotrifluoropropanediol derivative or a hydrate thereof with water in the presence of a base,
Equation (7) And a hydrate or an acetal derivative thereof (hereinafter referred to as reaction 1). (Wherein, X, Y and W represent the same meanings as described above) or a salt thereof with a mineral acid (hereinafter referred to as reaction 2).

The above reaction 1 is usually carried out at a pH of 12 or less, preferably in the range of about 2 to 9. When the pH exceeds 12, the fluorine of the trifluoromethyl group is also hydrolyzed at a considerable rate, so that the yield decreases and the purification becomes complicated. As the acid or base used for pH adjustment, known substances can be widely used. Specific examples of the acid include inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid and phosphoric acid, acetic acid, propionic acid, p
Organic acids such as toluenesulfonic acid, sodium dihydrogen phosphate, potassium dihydrogen phosphate, sodium bisulfite,
Examples thereof include acidic metal salts such as potassium hydrogen sulfite, and acidic ion exchange resins.

Specific examples of the base include basic salts such as hydroxides, carbonates, bicarbonates and acetates of alkali metals such as sodium and potassium or alkaline earth metals such as calcium and barium; And a nonionic ion exchange resin. It is also possible to use mixtures of the acids and bases indicated above.

The reaction is usually carried out in water, but it can also be carried out in a mixed solvent system of an organic solvent not involved in the reaction and water. The amount of water to be used is usually 0.5 to 100% by weight based on the dihalotrifluoroacetone derivative represented by the general formula (5) or the dihalotrifluoropropanediol derivative represented by the general formula (6) or a hydrate thereof. About twice,
Preferably, it is about 1 to 20 times by weight.

Examples of the organic solvent that can be used in such a reaction include hydrocarbon solvents such as benzene, toluene, and hexane; ether solvents such as tetrahydrofuran and methyl-t-butyl ether; and halogen solvents such as monochlorobenzene. No. The amount of the organic solvent used is not particularly limited.

The reaction temperature is usually in the range of about 0 ° C. to 100 ° C., but is preferably in the range of about 10 ° C. to 70 ° C. if the pH is 5 or less or in the range of 9 to 12, and is preferably in the range of 5 to 9 ° C. If it is within the range, the range is preferably from about 70 ° C to about 100 ° C.

After completion of the reaction, the reaction mixture is subjected to a conventional method, for example, an extraction treatment using an organic solvent, and the obtained organic layer is concentrated to obtain a carbonyl compound represented by the formula (7), a hydrate thereof, or acetate. To obtain a thiol derivative.
Further, if necessary, it can be purified by recrystallization, various types of chromatography and the like. Further, the aqueous solution of the carbonyl compound represented by the formula (7), a hydrate thereof, or an acetal derivative obtained by such a reaction can be used as it is in the next reaction.

The above reaction 2 is usually carried out in a solvent, and the reaction temperature is usually about 0 to 100 ° C., and the reaction time is usually about instant to about 72 hours. The amount of the reagent to be subjected to the reaction is represented by the general formula (8) based on 1 mol of the carbonyl compound represented by the formula (7) synthesized by the above reaction 1, or a hydrate thereof, or an acetal derivative. The hydrazine derivative to be used has a theoretical amount of 1 mole,
If necessary, an excess amount of the compound represented by the formula (7) can be used. The hydrazine derivative can also be used as a salt such as a hydrochloride or a sulfate.

In the above reaction, a solvent is usually used. Examples of such a solvent include aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether, aromatic hydrocarbons such as benzene, toluene and xylene. Chlorobenzene,
Halogenated hydrocarbons such as dichlorobenzene, ethers such as diethyl ether, diisopropyl ether, 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, and methyl tert-butyl ether; And alcohols such as ethanol, ethanol, ethylene glycol and isopropanol, water or a mixture thereof.

After completion of the reaction, the reaction solution is added with water as needed, and the resulting crystals are collected by filtration or subjected to ordinary post-treatments such as extraction with an organic solvent and concentration, and if necessary, chromatography. -The objective substance can be isolated by further purifying through operations such as recrystallization.

The hydrazine derivative represented by the general formula (8) and its salt with a mineral acid can be obtained by the production method described in JP-A-09-323977.

The pyridazine-3-compound represented by the general formula (4)
Specific examples of the ON derivative are shown in (Table 1), but the present invention is not limited to these.

[Table 1]

[0024]

Industrial Applicability According to the present invention, pyridazin-3-one derivatives having excellent herbicidal activity can be produced with high yield.

[0025]

EXAMPLES The present invention will be described in more detail with reference to the following Examples, which should not be construed as limiting the present invention. Example 1 g3 was added to heptane 20.97 under a nitrogen stream.
3,3-trifluoro-2-oxo-1- (4-chloro-2-fluoro-5-hydroxyphenylhydrazone)
20.94 g (purity 97.82%) of propanal, 13.17 g (purity 97%) of methylmalonic acid, 2-methyl-
9.01 g (purity 96.8%) of 5-ethylpyridine was added, and the mixture was heated to 80 ° C and stirred for 12 hours. To this solution were added, at the same temperature, 17.71 g (purity 96.8%) of 2-methyl-5 ethylpyridine and 2.70 g (purity 9) of calcium carbonate.
9.5%), and then heated to 105 ° C. to give 9.51 g.
After distilling off the liquid, the mixture was cooled to 35 ° C. Next, 38.62 g of toluene and 4.69 g of propionic acid were added,
The temperature was raised to 110 ° C., and heating and refluxing were performed for 32 hours while azeotropic dehydration. The reaction mass was cooled to 35 ° C., filtered through a glass filter, and the filtrate was concentrated to give 2-
A crude product of (2-fluoro-4-chloro-6-hydroxyphenyl) -5-trifluoromethylpyridazin-3-one was obtained. The yield was 70% from LC analysis. (Determined by an absolute calibration method using LC. Absolute calibration method: A solution in which the concentration of the target substance isolated in advance was changed was adjusted, and the detection intensity by liquid chromatography analysis was measured. Prepare a calibration curve.
Subsequently, the reaction solution after the completion of the reaction was prepared, the solution set in the range of the calibration curve was prepared, liquid chromatography analysis was performed, and the peak and area of the obtained target product were used to terminate the reaction using the calibration curve. It refers to a method of calculating the concentration of a target substance in a liquid to determine the yield. )

Claims (5)

[Claims] 1. The general formula (1) (Wherein, X represents a hydrogen atom or a halogen atom, Y represents a halogen atom, W is a hydrogen atom or a ZR ^1,, Z represents an oxygen atom or a sulfur atom, R ¹ represents a hydrogen atom, C1- C6 alkyl group, C1-C6 haloalkyl group, C
3-C8 cycloalkyl group, benzyl group, C3-C6 alkenyl group, C3-C6 haloalkenyl group, C3-C6 alkynyl group, C3-C6 haloalkynyl group, cyano C1-C6 alkyl group, C2-C8 (alkoxyalkyl) Group, C2-C8
(Alkylthioalkyl) group, carboxy C1-C6 alkyl group, (C1-C8 alkoxy) carbonyl C1-C6 alkyl group, {(C1-C4 alkoxy) C1-C4 alkoxy} carbonyl C1-C6 alkyl group, (C3-C8 cycloalkyl Alkoxy) carbonyl C1-C6 alkyl group, or
{(C1-C6 alkoxy) carbonyl C1-C6 alkyl} represents an oxycarbonyl C1-C6 alkyl group. ) And a malonic acid derivative represented by the general formula (2) R ² CH (COOH) ₂ (wherein R ² represents a hydrogen atom or a C1-C3 alkyl group), −
Reacting in the presence of 5-ethylpyridine to obtain a compound of the general formula (3) (Wherein, X, Y, W and R ² have the same meanings as described above), and then reacting with a carboxylic acid derivative represented by the formula (4) (Wherein, X, Y, W and R ² have the same meanings as described above). 2. The method for producing a pyridazin-3-one derivative according to claim 1, wherein the reaction is carried out in an organic solvent. 3. The process for producing a pyridazin-3-one derivative according to claim 1, wherein the organic solvent is a C7 to C15 aliphatic hydrocarbon, an optionally substituted aromatic hydrocarbon, or a mixture thereof. . 4. The condition for adding and reacting with an acid is that azeotropic dehydration and / or addition of a dehydrating agent is carried out while removing water produced by the reaction from the system. Pyridazine-3- according to 2, or 3
A method for producing an on derivative. 5. The process for producing a pyridazin-3-one derivative according to claim 1, wherein the reaction temperature is about 70 to 200 ° C.