JPH01168675A - Method for producing 1,3-dialkylpyrazole-5-carboxylic acid esters - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

Detailed Description of the Invention [Industrial Application Field] The present invention relates to a 1,3-dialkylpyrazole represented by the general formula (1) (wherein R, R' and R1 each represent a lower alkyl group) This invention relates to a method for producing -5-carboxylic acid esters.

The 1,3-dialkylpyrazole-5-carboxylic acid esters produced by the production method according to the present invention are useful as intermediates in the production of agricultural chemicals, particularly fungicides and herbicides.

[Conventional technology]

The method for producing 1,3-dialkylpyrazole-5-carboxylic acid esters is described in the Australian Journal of Chemistry (Au5t).

J. Cheea-), Vol. 36, pp. 135-147 (1983), acetopyruvate and methylhydrazine were reacted in ethanol to form 1,3-dimethyl, rub-ru-5-carboxylic acid ester, and 1.5. It is reported that a mixture of -dimethylpyrazole-3-carboxylic acid esters was obtained.

Also, V, Aue*ers+ K, and B
reyhan + T,)
AP, ), 143 (1935), 259, reports that when methyl 3-methylpyrazole-5-carboxylate is reacted with methyl iodide, only methyl 1,5-dimethylpyrazole-3-carboxylate is obtained. has been done.

[Problem that the invention seeks to solve]

The present inventors have published the above-mentioned Australian Journal of Chemistry (Au5t, J. Chew),
As a result of the reaction according to the synthesis conditions described in Volume 36, pages 135-147 (1983), 1.3-dimethylpyrazole-5-carboxylic acid esters and 1.5-dimethylpyrazole-3-carboxylic acid ester The generation ratio is 3/
It was obtained as a mixture of 7. That is, in the conventional method, the production ratio of the desired 1,3-dialkylpyrazole-5-carboxylic acid ester is at most 30%, and in N-alkylation with an alkyl halide, the production ratio of the desired 1,3-dialkylpyrazole-5-carboxylic acid ester is at most 30%. -There is a problem that carboxylic acid esters cannot be obtained.The present invention is directed to 1,3-dialkylpyrazole-5, which is useful as an intermediate for agricultural chemicals.
- It is an object of the present invention to provide a method for producing carboxylic acid esters that solves the above-mentioned problems and produces them with good regioselectivity.

[Means and actions for solving the problems] As a result of intensive studies to solve the above problems, it was found that good regioselectivity was achieved by using dialkyl sulfuric acid as an alkylating agent in the presence of a base and a phase transfer catalyst.1. It was discovered that 3-dialkylpyrazole-5-carboxylic acid ester could be obtained,
The invention has been completed.

That is, the present invention relates to 3(5)-methylpyrazole-5(3)-carboxylic acid esters represented by the general formula (II) 0+ (wherein R and R1 each represent a lower alkyl group) and the general A dialkyl sulfuric acid represented by the formula (III) (R'')zsOa (I[[) (in the formula, R1 represents a methyl group or an ethyl group) is reacted in the presence of a base and a phase transfer catalyst. This is a method for producing 1,3-dialkylpyrazole-5-carboxylic acid esters represented by the general formula (wherein R, R' and R1 each have the above-mentioned meanings).

The production method according to the present invention is 1,3-dialkylpyrazole-
This is a new method for producing 5-carboxylic acid esters, and the 1,3-dialkylpyrazole-5-carboxylic acid esters produced by the production method according to the present invention are pyrazoles useful as agricultural chemicals, especially fungicides and herbicides. It is useful as an intermediate in the production of carbonylaminoacetonitrile derivatives.

The production method according to the present invention is carried out according to the route shown in reaction formula (A).

Reaction formula (A) Mt. Hereinafter, the manufacturing method according to the present invention will be explained in detail.

Starting materials, e.g. 3(5)-methylpyrazole-5(3
)-carboxylic acid esters are available from the Australian Institute of Chemistry (Aust, J. Chem.),
It can be produced from acetopyruvate according to the following formula with reference to the method described in Vol. 36, pp. 135-147 (1983).

Other starting materials can be obtained by reacting in the same manner.

The production method according to the present invention comprises 3(
5) A base and a phase transfer catalyst are added to the -alkylpyrazole-5(3)-carboxylic acid ester, and a dialkyl sulfuric acid represented by the general formula (II[) is added while stirring. The reaction proceeds even in the absence of a base and a phase transfer catalyst, but it proceeds very easily in the presence of a base and a phase transfer catalyst;
．． The production rate of 3-dialkylpyrazole-5-carboxylic acid esters is dramatically improved.The reaction can be carried out in either an open or closed reaction vessel.The reaction temperature is 0°C.
-150°C, preferably 10-60°C.

Bases include alkali metal or alkaline earth metal oxides, hydroxides, and carbonates, and organic amines, specifically sodium hydroxide, potassium hydroxide, barium hydroxide, magnesium oxide, and calcium oxide. , sodium carbonate, sodium hydrogen carbonate, potassium carbonate, potassium hydrogen carbonate, calcium carbonate, triethylamine,
Examples include pyridine. These bases can be used in liquid or solid state. Preferred are potassium hydroxide, sodium hydroxide, potassium carbonate, sodium hydrogen carbonate, pyridine, and triethylamine. The amount used is 0.5 to 10 molar equivalents, preferably 1.5 to 10 molar equivalents per mole of the 3(5)-alkylpyrazole-5(3)-carboxylic acid ester represented by general formula (II).
It is 0 to 3.0 molar equivalent. If the amount of base used is small, the yield will be reduced. Further, if the amount is too large, it will not affect the yield in any way, but industrially it is desirable that the amount is 4.0 molar equivalent or less. The alkylating agent used in the production method of the present invention is diethyl sulfate or dimethyl sulfate. The amount used is 0.5 per mole of the 3(5)-alkylpyrazole-5(3)-carboxylic acid ester represented by the general formula (If).
mol or more, but from the viewpoint of yield and economic efficiency, it is 0.8 to 3
．． 0 mol is preferred.

Examples of the solvent used in the production method of the present invention include aromatic hydrocarbons, ethers, ketones, polar solvents, and esters. Preference is given to ethers such as tetrahydrofuran, polar solvents such as dimethylformamide.

The phase transfer catalysts used in the production method of the present invention are quaternary ammonium salts, quaternary phosphonium salts, and crown ethers. These phase transfer catalysts can be used in liquid or solid state.

The amount used is 0.1 to 50%, preferably 5.0 to 20%, based on the weight of the 3(5)-alkylpyrazole-5(3)-carboxylic acid ester represented by general formula (II).
%. If the amount of phase transfer catalyst is small, the yield will decrease. If it is too large, it will not affect the yield in any way, but industrially it is desirable that it be 20% or less. After the reaction is completed, it can be easily purified by distillation, recrystallization, or column chromatography.

〔Example〕

Hereinafter, the manufacturing method of the present invention will be specifically explained with reference to Examples.

Example 1 Synthesis of ethyl 1.3-dimethylpyrazole-5-carboxylate 1.8% potassium hydroxide in 30ml tetrahydrofuran
g (0,0272 mol), 0.3 g of triethylbenzylammonium chloride and 2.1 g of ethyl 3(5)-methylpyrazole-5(3)-carboxylate (0,013
6 mol) was added. Dimethyl sulfate 3.4 at room temperature under stirring
g (0,0272 mol) was added dropwise. The temperature was then raised to 60°C and stirred at the same temperature for 3 to 4 hours to complete the reaction.
The reaction was cooled to room temperature and condensed under reduced pressure. 50ml of water was added to the residue, and the mixture was extracted three times with 50ml of ethyl acetate. The organic layers were combined and washed with saturated brine, then dried over sodium sulfate, and then distilled under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography.

Elution with a hexane-ethyl acetate system yielded 2.1 g of desired ethyl 1,3-dimethyl and lab-ru-5-carboxylate. Yield 91.8% Oily DCIs δ (ppm): 1.36 (3H, t, J-7,
0H2), MS 2.25 (3H, s), 4.09 (3) 1. s), 4.
29 (2H, Q, J・7.0H2), 6.63 (LH,
s) Example 2 Synthesis of ethyl 1-ethyl-3-methylpyrazole-5-carboxylate 1.6 ml of triethylamine in 30 ml of tetrahydrofuran
g (0,0163 mol) and 0.3 g triethylbenzylammonium bromide and 2.1 g (0,01
36 mol) was added. diethyl sulfate at room temperature under stirring
．． 5 g (0,0163 mol) was added dropwise. Then 60'
The temperature was raised to C. and the mixture was stirred at the same temperature for 4 to 5 hours to complete the reaction.

The reaction was cooled to room temperature and concentrated under reduced pressure. The residue was purified by silica gel column chromatography. Elution with hexane-ethyl acetate system yielded 2.1 g of the desired 1-ethyl-3-methylpyrazole-5-carboxylic acid. Yield 90.7% Oily 6 CD" (PI): 1.3-1.6 (6
B, m), 2.25 (38, s), T gate S 4.1-4.6 (4Hv), 6.60 (IH, s) [
[Effects of the Invention] The method for producing 1,3-dialkylpyrazole-5-carboxylic acid esters according to the present invention overcomes the drawbacks of conventional methods such as large amounts of positional isomers being produced as by-products and low yields, and enables positional selection. This makes it possible to synthesize the target product in a highly efficient manner and in high yield.

Moreover, l produced by the production method according to the present invention.

3-Dialkylpyrazole-5-carboxylic acid esters are used as intermediates in the production of pyrazolecarbonylaminoacetonitriles, which have excellent broad control effects as fungicides and herbicides, especially fungicides for agriculture and horticulture. is extremely useful industrially.

Claims (1)

[Claims] General formula (II) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(II) (In the formula, R and R^1 each represent a lower alkyl group) 3(5)- Methyl pyrazole-5(3)-carboxylic acid esters and dialkyl sulfuric acid represented by the general formula (III) (R^2)_2SO_4(III) (in the formula, R^2 represents a methyl group or an ethyl group). In the presence of a base and a phase transfer catalyst,
General formula (I) characterized by reaction ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (I) (In the formula, R, R^1 and R^2 each have the above meanings) Represented by Method for producing 1,3-dialkylpyrazole-5-carboxylic acid esters.