JPH0632783A - Production of 5-oxo-1h-pyrazole-4-carboxylate ester - Google Patents

Abstract

PURPOSE:To simply obtain the subject compound useful as a raw material for medicines, agricultural chemicals, etc., by reacting a 1H-pyrazol-5-one compound with a halogenocarbonic acid ester in the presence of a base without passing through a relatively unstable intermediate. CONSTITUTION:A compound of formula I (R<1>, R<2> are alkyl, aryl) is reacted with a compound of formula II (R<3> is lower alkyl; X is halogen, alkylsulfonyloxy, etc.,) (preferably methyl chlorocarbonate) in the presence of a base such as triethylamine, N,N-ethylaniline or pyridine in a solvent, preferably benzene, chloroform, preferably at 40-80 deg.C for 0.5-48hr to obtain the objective compound of formula III, e.g. 4,5-dihydro-1,3-dimethyl-5-oxo-1H-pyrazole-4- carboxylic acid ethyl ester.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing 5-oxo-1H-pyrazole-4-carboxylic acid ester useful as a raw material compound for medicines, agricultural chemicals, electronic materials and the like.

[0002]

As a method for producing 1H-pyrazole-4-carboxylic acid ester, a method of reacting an acylmalonic acid ester with hydrazine (J. Chem. Soc., 1
501 (1951)), a method of reacting ethoxymethylene malonate with hydrazine (Ber, vol2).
8, 35 (1895)), a method of reacting aminomethylidine malonate with hydrazine (Ann, vol.
578, 48 (1952), Ber, vol27, 27.
43 (1894)) is known.

[0003]

However, these conventional methods are methods for finally forming a pyrazolone ring, and are relatively unstable such as acylmalonic acid ester, ethoxymethylenemalonic acid ester, and aminomethylidynemalonic acid ester. There was a problem that we had to go through an intermediate.

The present inventor diligently studied a method for producing 5-oxo-1H-pyrazole-4-carboxylic acid ester in order to solve the above problems, and as a result, 1H-pyrazole-
The present inventors have found that a 5-oxo-1H-pyrazole-4-carboxylic acid ester can be easily produced by reacting a 5-one with a halocarbonic acid ester in the presence of a base, and completed the present invention.

[0005]

That is, the present invention is based on the general formula (1):

[Chemical 4] (In the formula, R ¹ and R ² represent the same or different alkyl groups or aryl groups) 1H-pyrazole-5
A compound of the general formula (2) in the presence of a base,

[Chemical 5] (Wherein R ³ is a lower alkyl group, X is a halogen atom, an alkylsulfonyloxy group, a haloalkylsulfonyloxy group or an arylsulfonyloxy group) and is reacted with a halocarbonic acid ester represented by the general formula (3),

[Chemical 6] (In the formula, R ¹ , R ² and R ³ are the same as the above-mentioned groups), and a process for producing a 5-oxo-1H-pyrazole-4-carboxylic acid ester.

1H-pyrazole-5 used in the present invention
Examples of the substituents R ¹ and R ^{2 of the} -ones include a methyl group, an ethyl group, an n-propyl group, an n-butyl group, an i-butyl group, an n-pentyl group, a 2-methylbutyl group and a 3-methylbutyl group. And other alkyl groups, phenyl groups, 2-chlorophenyl groups, 3-chlorophenyl groups, 4-chlorophenyl groups, 2,3-dichlorophenyl groups, 2,4-dichlorophenyl groups, 2,5-dichlorophenyl groups, 2,6-dichlorophenyl groups , 3,4-dichlorophenyl group, 3,
5-dichlorophenyl group, 1-naphthyl group, 2-chloro-1-naphthyl group, 4-chloro-1-naphthyl group, 2-
Examples of the aryl group include a naphthyl group, a 1-chloro-2-naphthyl group, a 4-chloro-2-naphthyl group and the like.

R ³ of the halocarbonic acid ester is, for example, methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, i-butyl group, sec-butyl group,
t-butyl group, n-pentyl group, 1-methylbutyl group,
Examples thereof include lower alkyl groups such as 2-methylbutyl group, 3-methylbutyl group and neo-pentyl group.

Examples of the halogen atom as X in the halocarbonic acid ester include chlorine and bromine. Examples of the alkylsulfonyloxy group include a methylsulfonyloxy group and an ethylsulfonyloxy group. Examples of the haloalkylsulfonyloxy group include a chloromethylsulfonyloxy group and a bromomethylsulfonyloxy group. As the arylsulfonyloxy group, a phenylsulfonyloxy group, a p-tolylsulfonyloxy group, 1-
Examples thereof include a naphthylsulfonyloxy group and a 2-naphthylsulfonyloxy group.

The reaction of the present invention is carried out in a solution or suspension state, but is preferably carried out using a solvent. The solvent is not limited as long as it is inert to the reaction,
For example, aromatic hydrocarbons such as benzene, toluene and xylene, halogenated hydrocarbons such as dichloroethane, chloroform, 1,2-dichloroethane, 1,1,1-trichloroethane, tetrachloroethylene, chlorobenzene and o-dichlorobenzene, diethyl ether. , Diisopropyl ether, tetrahydrofuran, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, triethylene glycol dimethyl ether,
Ethers such as dioxane, N, N-dimethylformamide, N-methylpyrrolidone, 1,3-dimethyl-2-
Examples thereof include aprotic polar solvents such as imidazolidinone, dimethyl sulfoxide and sulfolane, and organic bases such as pyridine and pyricon. It is also possible to mix these solvents and use them as a reaction solvent.

As the base, triethylamine,
N, N-diethylaniline, pyridine, α-pyricon,
Examples include γ-picoline and 2-methyl-5-ethylpyridine. The base may be used in an equimolar amount or more, preferably in the range of about 1.0 to 2.0 mol, based on 1 mol of 1H-pyrazol-5-ones. The amount of the halocarbonic acid ester to be used may be 1 mol or more of 1H-pyrazol-5-ones in an equimolar amount or more, preferably about 1.0 to
It is in the range of 2.0 mol.

The reaction temperature is selected from room temperature to the boiling point of each solvent, preferably in the range of 40 to 80 ° C.
The reaction time varies depending on the amount of the reactants, the reaction temperature, etc., but is selected from the range of about 0.5 to 48 hours. After completion of the reaction, the target compound, 5-oxo-1H-pyrazole-4-carboxylic acid ester, can be obtained by performing a conventional operation such as injecting water into the reaction solution and extracting with an organic solvent. it can. The 5-oxo-1H-pyrazole-4-carboxylic acid ester is used as it is, or if necessary, distilled,
It can be further purified by means of recrystallization, chromatography or the like and provided as a raw material compound.

[0012]

According to the method of the present invention, 5-oxo-1H
-Pyrazole-4-carboxylic acid ester can be easily produced in good yield.

[0013]

EXAMPLES The present invention will be described in more detail with reference to examples, but the present invention is not limited to the following examples.

Example 1 To 44.85 g (0.40 mol) of 4,5-dihydro-1,3-dimethyl-1H-pyrazol-5-one 1,2-
400 g of dichloroethane and 34.80 g of pyridine
(0.44 mol) was added, and the mixture was heated to 60 ° C. 47.75 g (0.44 mol) of ethyl chlorocarbonate was added thereto at 60 ° C.
Was added dropwise over 30 minutes, and the mixture was kept at 60 ° C. for 1 hour. After cooling the reaction solution to room temperature, 400 g of water was injected, the organic layer was separated, and the aqueous layer was extracted with 200 g of 1,2-dichloroethane. The organic layers are combined, dried over anhydrous magnesium sulfate,
After magnesium sulfate was filtered off, the solution was concentrated under reduced pressure. The obtained residue is distilled under reduced pressure (boiling point: 102-103 ° C / 3.5 mmH
g) and ethyl 4,5-dihydro-1,3-dimethyl-5-oxo-1H-pyrazole-4-carboxylate 56.
49 g were obtained. (Yield 76.7%).

Example 2 41.58 g (0.44 mol) of methyl chlorocarbonate was used in place of the ethyl chlorocarbonate of Example 1, the same reaction and post-treatment were carried out to give 4,5-dihydro-1,3. Methyl dimethyl-5-oxo-1H-pyrazole-4-carboxylate (boiling point: 98-104 ° C / 4.0 mmHg) 46.87
g was obtained. (Yield 68.9%).

Claims (3)

[Claims] 1. A compound represented by the general formula (1): (In the formula, R ¹ and R ² represent the same or different alkyl groups or aryl groups) 1H-pyrazole-5
In the presence of a base, the -ones are represented by the general formula (2): (Wherein R ³ is a lower alkyl group, X is a halogen atom, an alkylsulfonyloxy group, a haloalkylsulfonyloxy group or an arylsulfonyloxy group) and is reacted with a halocarbonic acid ester. (3), embedded image (In the formula, R ¹ , R ² and R ³ are the same as the above-mentioned groups) A process for producing a 5-oxo-1H-pyrazole-4-carboxylic acid ester. 2. The base is at least one compound selected from the group consisting of triethylamine, N, N-diethylaniline, pyridine, α-pyricon, γ-picoline and 2-methyl-5-ethylpyridine. A method for producing the described 5-oxo-1H-pyrazole-4-carboxylic acid ester. 3. The method for producing a 5-oxo-1H-pyrazole-4-carboxylic acid ester according to claim 1, wherein the halocarbonic acid ester is methyl chlorocarbonate or ethyl chlorocarbonate.