WO2017114121A1

WO2017114121A1 - Method for preparing pyridylpyrazolidone carboxylic acid compound

Info

Publication number: WO2017114121A1
Application number: PCT/CN2016/108984
Authority: WO
Inventors: 于海波; 王学玲; 赵贵民; 黄耀师; 徐凤波; 杨辉斌; 李斌
Original assignee: 沈阳中化农药化工研发有限公司
Priority date: 2015-12-29
Filing date: 2016-12-08
Publication date: 2017-07-06
Also published as: CN106928183B; CN108137535B; CN108137535A; BR112018013249B1; CN106928183A; BR112018013249A2

Abstract

The present invention belongs to the field of organic synthesis, and in particular relates to a method for preparing a pyridylpyrazolidone carboxylate compound. The reaction formula is as follows and the definition for each group in the formula can be found in the description. The present invention provides a method for preparing a pyridylpyrazolidone carboxylate compound that is a key intermediate of benzamide insecticides. By employing the method of the present invention, the yield of products is increased, and the energy consumption is reduced. The method of the present invention is more easily to be used in the industrial production.

Description

Method for preparing pyridylpyrazolidinone carboxylic acid compound

Technical field

The invention belongs to the field of organic synthesis, and in particular relates to a method for preparing a pyridylpyrazolidinone carboxylate compound.

Background technique

Benzoylamides are a class of highly effective and safe new insecticides. Wherein 3-bromo-N-(2-methyl-4-chloro-6-(carbamoyl)phenyl)-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-carboxamide (common name: chlorantraniliprole), 3-bromo-N-(2-methyl-4-cyano-6-(carbamoyl)phenyl)-1-(3-chloro-2-pyridyl)-1H- Pyrazole-5-carboxamide (common name cyantraniliprole) has high insecticidal activity and DuPont has developed insecticides. The bisamide compound being developed by Ishihara Sangyo Co., Ltd. 3-bromo-N-(2-chloro-4-bromo-6-((1-cyclopropylethyl) acyl)phenyl)-1-(3-chloro 2-pyridyl)-1H-pyrazole-5-carboxamide (common name: cyclaniliprole) has a broad spectrum of insecticidal activity. Shenyang Institute of Chemical Industry found 3-bromo-N-(2,4-dichloro-6-(carbamoyl)phenyl)-1-(3,5-dichloro-2-pyridine) with high insecticidal activity -1H-pyrazole-5-carboxamide, also developed as an insecticide, is commonly known as tetrachlorazamide.

1-(3-Chloropyridin-2-yl)-3-pyrazolidinone-5-carboxylate is a common key intermediate for the synthesis of chlorantraniliprole, cyantraniliprole, cyclaniliprole, and 1-(3-chloropyridine) is disclosed in WO2004011453. The synthesis of 2-yl)-3-pyrazolidinone-5-carboxylate is obtained by reacting mercaptopyridine with maleic acid diester at reflux temperature, and the reaction yield is only 55%.

Xu Fengbo, from Nankai University, reported the synthesis of ethyl 1-(3-chloropyridin-2-yl)-3-pyrazolidin-5-carboxylate using a complex guanidine ring-containing bisamine complex A as a catalyst. Method (Reference: Pesticide Research and Application. 14(2), 14-15, 2009), yield 70%. The specific structure of the catalyst is as follows:

For a long time, technicians have been working on the development of new, more advanced and rational pyridylpyrazolidinone carboxylate compounds in order to obtain better quality and lower price benzamide insecticides.

Summary of the invention

It is an object of the present invention to provide a process for the preparation of a pyridylpyrazolidinone carboxylate compound which is simpler and more efficient.

In order to achieve the above object, the technical solution adopted by the present invention is:

A method for preparing a pyridylpyrazolidinone carboxylate compound, the reaction formula is as follows:

Wherein R _{1 is} selected from H or Cl; and R _{2 is} selected from C ₁ -C ₆ alkyl, C ₂ -C ₄ alkenyl, C ₂ -C ₄ alkynyl, C ₃ -C ₆ cycloalkyl, halogen, a benzyl group which is unsubstituted or substituted with up to 6 C ₁ -C ₄ alkyl groups;

Pyridylpyridine (II) is obtained by reacting a maleic acid diester (III) with a maleic acid diester (III) under basic conditions to obtain a pyridylpyrazolidinone carboxylate compound (I).

Wherein the catalyst is selected from: Cu (L1) Cl, Cu (L1) Br, Cu (L1) I, Cu (L2) 2 Cl, Cu (L2) 2 Br, Cu (L2) 2 I, Ni (L1) Cl _{_{2, Ni (L1) Br 2}} , Ni (L1) I 2, Ni (L2) 2 Cl 2, Ni (L2) 2 Br 2 or Ni (L2) _₂ I _2; wherein L1 is selected from:

L2 is selected from:

The catalyst is selected from the group consisting of Cu(L1)Br, Cu(L1)I, Cu(L2) ₂ Br or Cu(L2) ₂ I;

L1 is selected from:

L2 is selected from:

The catalyst is selected from Cu(L1)I or Cu(L2) ₂ I, wherein

L1 is selected from:

L2 is selected from:

The step of preparing a pyridylpyrazolidinone carboxylate compound (I) by reacting a pyridylpyridine (II) with a maleic acid diester (III) under the action of a catalyst under basic conditions includes,

The molar ratio of the mercaptopyridine (II), the base, the maleic acid diester (III) and the catalyst is from 1:1 to 2:1 to 5:0.00001 to 0.01.

The molar ratio of the mercaptopyridine (II), the base, the maleic acid diester (III) and the catalyst is 1:1.2-1.5:1.5-2:0.0001-0.001;

The pyridylpyridine (II) is subjected to a reaction with a maleic acid diester (III) under basic conditions to obtain a pyridylpyrazolidinone carboxylate compound (I), and the reaction temperature is controlled. 20-50 ° C.

The reaction of the pyrithione (II) with a maleic acid diester (III) by a catalyst under basic conditions to obtain a pyridylpyrazolidinone carboxylate compound (I) is carried out in the following solvent:

The solvent is toluene, chlorobenzene, carboxylic acid esters, alkyl alcohols, ethers or polar aprotic solvents;

The base employed is selected from the group consisting of alkali metal hydrides, alkali metal amides or alkyl alcoholates.

The hydride of the alkali metal is lithium hydride, sodium hydride or potassium hydride;

The alkali metal amide is lithium amide, sodium amide or potassium amide; the alkyl alcoholate is sodium methoxide, sodium ethoxide, sodium propoxide, sodium butoxide, sodium pentoxide, sodium isopropoxide, sodium isobutoxide, sec Sodium alkoxide, sodium t-butoxide, potassium methoxide, potassium ethoxide, potassium propoxide or potassium t-butoxide;

The carboxylic acid esters are acetate, fumaric acid diester or maleic acid diester; alkyl alcohols are methanol, ethanol, propanol, butanol, pentanol, isopropanol, isobutanol, secondary Butanol or tert-butanol; ethers are tetrahydrofuran, 2-methyltetrahydrofuran or dioxane; polar aprotic solvents are acetonitrile, N,N-dimethylformamide, N,N-dimethyl Amide or dimethyl sulfoxide.

The base is selected from the group consisting of sodium methoxide, sodium ethoxide, sodium propoxide, sodium butoxide, sodium pentoxide, sodium isopropoxide, sodium isobutoxide, sodium sec-butoxide or sodium t-butoxide;

Suitable solvents are selected from the group consisting of methanol, ethanol, propanol, butanol, pentanol, isopropanol, isobutanol, sec-butanol or tert-butanol.

The base is selected from sodium ethoxide; the suitable solvent is selected from the group consisting of ethanol.

In the synthetic methods given above and the definitions of the groups in the compounds of the general formula, the terms used in the collection are generally defined as follows:

Alkyl means straight-chain or branched form, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, etc. Group. The cycloalkyl group means a group including a cyclic chain form such as a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a methylcyclopropyl group, a cyclopropylcyclopropyl group or the like. The alkenyl group means a linear or branched alkenyl group such as a 1-propenyl group, a 2-propenyl group and a different butenyl group. Alkynyl means a straight or branched alkyne such as 1-propynyl, 2-propynyl and the different butynyl groups and the like. Halogen means fluorine, chlorine, bromine or iodine.

The present invention has a point: the present invention employs a simple nitrogen-free phenylphosphine compound as a catalyst for catalyzing the synthesis of a pyridylpyrazolidinone carboxylate, which can greatly improve the yield of the reaction, thereby completing the present invention.

Alternatively, the reaction of the preparation method of the present invention can be carried out at 20 to 50 ° C, and the temperature is easily controlled, so that the safety of the reaction is greatly improved. In addition, the catalyst of the invention has the advantages of simple synthesis and low cost, and can be prepared only by reacting a metal salt and a phenylphosphine in ethanol. Therefore, the catalyst of the present invention is easier to use in industrial production.

detailed description

Hereinafter, the present invention will be described in more detail by way of examples, but the present invention is not intended to limit the invention.

Example 1

Synthesis of ethyl 1-(3-chloropyridin-2-yl)-3-pyrazolidinone-5-carboxylate

1000 ml of absolute ethanol and sodium ethoxide (65.7 g, 0.966 mol), 3-chloro-2-mercaptopyridine (101.04 g, 98%, 0.69 mol) were added to a 2000 ml reaction flask, followed by addition of a catalyst Cu (PPh _{3 ).} ₂ I (0.15 g, 0.00021 mol) (bistriphenylphosphine cuprous iodide, synthetic method participation: Chemistry-A European Journal, 16 (39), 11822-11826, 2010) mixture heated to 40 ° C, dripping Diethyl maleate (145.7 g, 0.83 mol). This temperature was maintained for 4 h and then the reaction mixture was neutralized with glacial acetic acid (60 g). The mixture was diluted with 1000 ml of water, cooled to room temperature and solids precipitated. The solid was collected by filtration and washed with 3×150 ml of 40% aqueous ethanol. After drying, 149.91 g of an orange solid of 1-(3-chloro-2-pyridyl)-3-pyrazolidinone-5-carboxylate was obtained, which was quantitatively analyzed by external standard method to be 98%, yield 79%. ^{1 H NMR (300MHz, DMSO)} : 8.289-8.269 (q, 1H), 7.956-7.190 (q, 1H), 7.231-7.190 (q, 1H), 4.862-4.816 (q, 1H), 4.236-4.165 (q , 2H), 2.967-2.879 (q, 1H), 2.396-2.336 (q, 1H), 1.250-1.202 (t, 3H).

The synthesis method of the catalyst is as follows:

1000 ml of absolute ethanol, triphenylphosphine (500 g, 1,9 mol), CuI (181 g, 0.95 mol) were sequentially added to a 2000 ml reaction flask, and the mixture was heated to 80 ° C for 1 h, and then naturally cooled to room temperature and filtered. , dried, yielded 644.9 g of product, yield 95%.

The selection of suitable starting materials for the other catalysts described below can be prepared in this manner.

Example 2

Synthesis of ethyl 1-(3-chloropyridin-2-yl)-3-pyrazolidinone-5-carboxylate

In a 1000 ml reaction flask, 300 ml of absolute ethanol and sodium ethoxide (16.97 g, 0.249 mol), 3-chloro-2-mercaptopyridine (30.75 g, 98%, 0.21 mol) were added, followed by the addition of catalyst Cu (binap). I (0.017 g, 0.00021 mol) (2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl abbreviated as binap, synthesis method participation: Chemistry-A European Journal, 16 (39), 11822- 11826, 2010) The mixture is heated to 30 ° C, dripping

Diethyl maleate (44.23 g, 0.252 mol). This temperature was maintained for 4 h and then the reaction mixture was neutralized with glacial acetic acid (15 g,). The mixture was diluted with 300 ml of water and cooled to room temperature to precipitate a solid. The solid was collected by filtration and washed with 3×50 mL of 40% aqueous ethanol. After drying, 47.06 g of an orange solid of 1-(3-chloro-2-pyridyl)-3-pyrazolidinone-5-carboxylate was obtained, which was quantitatively analyzed by external standard method to be 95%, yield 79%.

Example 3

Synthesis of ethyl 1-(3-chloropyridin-2-yl)-3-pyrazolidinone-5-carboxylate

In a 1000 ml reaction flask, 300 ml of absolute ethanol and sodium ethoxide (16.97 g, 0.249 mol), 3-chloro-2-mercaptopyridine (30.75 g, 98%, 0.21 mol) were added, followed by the addition of catalyst Cu (PPh _{3 ).} ₂ Br (0.042 g, 0.000063 mol) (bistriphenylphosphine bromide, synthetic method participation: Chemistry-A European Journal, 16 (39), 11822-11826, 2010), the mixture is heated to 35 ° C, dripping Diethyl maleate (44.23 g, 0.252 mol). This temperature was maintained for 4 h and then the reaction mixture was neutralized with glacial acetic acid (15 g). The mixture was diluted with 300 ml of water and cooled to room temperature to precipitate a solid. The solid was collected by filtration and washed with 3×50 mL of 40% aqueous ethanol. After drying, ethyl l-(3-chloro-2-pyridyl)-3-pyrazolidinone-5-carboxylate was obtained as an orange solid, 45.98 g, which was quantitatively analyzed by external standard method to be 96%, yield 78%.

Example 4

Synthesis of ethyl 1-(3-chloropyridin-2-yl)-3-pyrazolidinone-5-carboxylate

In a 1000 ml reaction flask, 300 ml of absolute ethanol and sodium ethoxide (16.97 g, 0.249 mol), 3-chloro-2-mercaptopyridine (30.75 g, 98%, 0.21 mol) were added, followed by the addition of catalyst Ni (PPh _{3 ).} ₂ Br ₂ (0.047 g, 0.000063 mol) (bis-triphenylphosphine nickel dibromide synthesis method: Appl. Organometal. Chem., 23, 455-459, 2009), the mixture is heated to 45 ° C, maleic acid is added dropwise Diethyl ester (44.23 g, 0.252 mol). This temperature was maintained for 4 h and then the reaction mixture was neutralized with glacial acetic acid (15 g). The mixture was diluted with 300 ml of water and cooled to room temperature to precipitate a solid. The solid was collected by filtration and washed with 3×50 mL of 40% aqueous ethanol. After drying, 45.98 g of an orange solid of ethyl 1-(3-chloro-2-pyridyl)-3-pyrazolidinone-5-carboxylate was obtained, which was quantitatively analyzed by external standard method to be 96%, yield 78%.

According to the method in Example 1, the catalyst Cu(PPh ₃ ) ₂ I (bistriphenylphosphine cuprous iodide) can be used to obtain 1-(3,5-dichloropyridin-2-yl) in high yield. Ethyl-3-pyrazolidinone-5-carboxylate. ^{_{1 H NMR (300MHz, CDCl 3}} ): 8.146 (q, 1H), 7.658 (q, 1H), 5.073 (dd, 1H), 4.241 (q, 2H), 3.029 (dd, 1H), 2.721 (dd, 1H ), 1.258 (t, 3H).

Example 5

Synthesis of ethyl 1-(3-chloropyridin-2-yl)-3-pyrazolidinone-5-carboxylate

600 liters of anhydrous ethanol and sodium ethoxide (34.6 kg, 500 mol), 3-chloro-2-mercaptopyridine (61.5 kg, 98%, 420 kmol) were added to a 1000 liter autoclave, followed by the addition of catalyst Cu ( PPh ₃ ) ₂ I (90 g), the mixture was heated to 35 ° C, and diethyl maleate (88.4 kg, 500 mol) was added dropwise. This temperature was maintained for 4 h and then the reaction mixture was neutralized with glacial acetic acid (20 kg). The mixture was diluted with 300 liters of water and cooled to room temperature with solids. The solid was collected by filtration and beaten with 100 liters of 40% aqueous ethanol. After centrifugation and drying, the crude solid of ethyl 1-(3-chloro-2-pyridyl)-3-pyrazolidinone-5-carboxylate was 92 kg, and the content was 96% by external standard method. The rate is 78%.

Comparative example

1-(3-Chloropyridin-2-yl)-3-pyrazolidinone-5-carboxy was synthesized according to the open method of Nankai University (Reference: Pesticide Research and Application. 14(2), 14-15, 2009) Ethyl acetate.

300 ml of absolute ethanol and sodium (5.22 g, 0.227 mol) were added to a 1000 ml reaction flask, stirred until no bubbles were formed, 3-chloro-2-mercaptopyridine (30.00 g, 0.205 mol) was added and the mixture was heated to After refluxing for 5 min, 0.003 g of catalyst A was further added, and diethyl maleate (36.00 g, 0.209 mol) was added dropwise. The reflux was maintained for 30 min and then the reaction mixture was cooled to 65.degree. C. and neutralized with glacial acetic acid (25.2 g). The mixture was diluted with 300 ml of water and cooled to room temperature to precipitate a solid. The solid was collected by filtration and washed with 3×50 mL of 40% aqueous ethanol. After drying, ethyl 1-(3-chloro-2-pyridyl)-3-pyrazolidinone-5-carboxylate was obtained, 45.2 g of an orange solid, with a normal content of 96%, and its content was 85.4% by external standard method. The yield is 70%.

It can be seen from the above various examples and comparative examples that the present invention uses a nitrogen-free phenylphosphine compound which is simple in structure and inexpensive to obtain as a catalyst, and obtains a pyridylpyrazolidinone carboxylate compound in a relatively high yield. And got an industrial magnification application. After using the catalyst of the invention, the reaction can be carried out at a lower temperature, which reduces the production energy consumption and greatly increases the safety of the reaction, which plays an important role in reducing production cost and improving reaction safety in the production process.

Applications

According to the above reaction formula, the ethyl 3-chloropyridylpyrazolidinonecarboxylate obtained in the above examples was subjected to bromination and hydrolysis to give 3-bromo-1-pyridylpyrazole-5-carboxylic acid. The pyrazole carboxylic acid obtained by hydrolysis is further acylated and oxidized to obtain pyrazole oxychloride, and then reacted with 2-amino-3-methyl-5-chlorobenzoylmethylamine to obtain a commercial chlorantraniliprole. The rate was 56.7% (calculated as ethyl 3-chloropyridylpyrazolidinone).

Claims

A method for preparing a pyridylpyrazolidinone carboxylate compound, characterized in that:

The reaction formula is as follows:

Wherein R 1 is selected from H or Cl; and R 2 is selected from C 1 -C 6 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 3 -C 6 cycloalkyl, halogen, a benzyl group which is unsubstituted or substituted with up to 6 C 1 -C 4 alkyl groups;

Pyridylpyridine (II) is obtained by reacting a maleic acid diester (III) with a maleic acid diester (III) under basic conditions to obtain a pyridylpyrazolidinone carboxylate compound (I).

Wherein the catalyst is selected from: Cu (L1) Cl, Cu (L1) Br, Cu (L1) I, Cu (L2) 2 Cl, Cu (L2) 2 Br, Cu (L2) 2 I, Ni (L1) Cl 2, Ni (L1) Br 2 , Ni (L1) I 2, Ni (L2) 2 Cl 2, Ni (L2) 2 Br 2 or Ni (L2) 2 I 2;

Where L1 is selected from:

L2 is selected from:
The method for producing a pyridylpyrazolidinone carboxylate compound according to claim 1, wherein:

The catalyst is selected from the group consisting of Cu(L1)Br, Cu(L1)I, Cu(L2) 2 Br or Cu(L2) 2 I;

L1 is selected from:

L2 is selected from:
The method of preparing the ester compound pyridyl pyrazolidinone carboxylic acid according to claim 2, wherein: said catalyst is selected from Cu (L1) I or Cu (L2) 2 I, wherein

L1 is selected from:

L2 is selected from:
The method for producing a pyridylpyrazolidinone carboxylate compound according to claim 1, wherein the pyridylpyridine (II) is subjected to a catalyst and a maleic acid diester under basic conditions. III) The step of preparing the pyridylpyrazolidinone carboxylate compound (I) by the reaction includes

The molar ratio of the mercaptopyridine (II), the base, the maleic acid diester (III) and the catalyst is from 1:1 to 2:1 to 5:0.00001 to 0.01.
The method for preparing a pyridylpyrazolidinone carboxylate compound according to claim 4, characterized in that the molar combination of the mercaptopyridine (II), the base, the maleic acid diester (III) and the catalyst The ratio is 1:1.2-1.5:1.5-2: 0.0001-0.001.
The method for preparing a pyridylpyrazolidinone carboxylate compound according to claim 1, wherein the mercaptopyridine (II) is reacted with a maleic acid diester (III) under basic conditions. In the step of preparing the pyridylpyrazolidinone carboxylate compound (I), the reaction temperature is controlled to be 20 to 50 °C.
The method for preparing a pyridylpyrazolidinone carboxylate compound according to claim 1, wherein the mercaptopyridine (II) is reacted with a maleic acid diester (III) under basic conditions. The reaction for producing the pyridylpyrazolidinone carboxylate compound (I) is carried out in the following solvent:

The solvent is toluene, chlorobenzene, carboxylic acid esters, alkyl alcohols, ethers or polar aprotic solvents;

The base employed is selected from the group consisting of alkali metal hydrides, alkali metal amides or alkyl alcoholates.
The method for preparing a pyridylpyrazolidinone carboxylate compound according to claim 7, wherein the alkali metal hydride is lithium hydride, sodium hydride or potassium hydride;

The alkali metal amide is lithium amide, sodium amide or potassium amide; the alkyl alcoholate is sodium methoxide, sodium ethoxide, sodium propoxide, sodium butoxide, sodium pentoxide, sodium isopropoxide, sodium isobutoxide, sec Sodium alkoxide, sodium t-butoxide, potassium methoxide, potassium ethoxide, potassium propoxide or potassium t-butoxide;

The carboxylic acid esters are acetate, fumaric acid diester or maleic acid diester; alkyl alcohols are methanol, ethanol, propanol, butanol, pentanol, isopropanol, isobutanol, secondary Butanol or tert-butanol; ethers are tetrahydrofuran, 2-methyltetrahydrofuran or dioxane; polar aprotic solvents are acetonitrile, N,N-dimethylformamide, N,N-dimethyl Amide or dimethyl sulfoxide.
The method for preparing a pyridylpyrazolidinone carboxylate compound according to claim 8, wherein the base is selected from the group consisting of sodium methoxide, sodium ethoxide, sodium propoxide, sodium butoxide, and sodium pentoxide. Sodium propoxide, sodium isobutoxide, sodium sec-butoxide or sodium t-butoxide;

The solvent is selected from the group consisting of methanol, ethanol, propanol, butanol, pentanol, isopropanol, isobutanol, sec-butanol or tert-butanol.
The method for producing a pyridylpyrazolidinone carboxylate compound according to claim 9, wherein the base is selected from the group consisting of sodium ethoxide; and the solvent is selected from the group consisting of ethanol.