Method for producing cyclopropylacetaldehyde

Abstract

Providing an industrially advantageous method for producing cyclopropylacetaldehyde. [Solution] General formula (I) [Formula 1] To establish a safe and industrially advantageous method for efficiently producing cyclopropylacetaldehyde, which can be used as a raw material for insecticides, by adding water to readily available and relatively inexpensive cyclopropylacetylene using a ruthenium catalyst and mainly bidentate ligands in the presence of a solvent under an inert gas atmosphere such as nitrogen gas.

Description

[Technical Field]

[0001] The present invention relates to a method for producing cyclopropylacetaldehyde using a ruthenium catalyst. [Background technology]

[0002] Cyclopropylacetaldehyde is useful as a raw material for the synthesis of pharmaceuticals or agricultural chemicals. Patent Document 1 describes a method for producing tetrahydrodisilylalkane compounds by synthesizing them using cyclopropylacetylene, a chiral cobalt complex, and a silane compound, followed by oxidation. Patent Document 2 describes a method for producing trihydrodisilylalkane compounds by synthesizing them using cyclopropylacetylene, a chiral cobalt complex, and a silane compound, followed by oxidation. Patent Document 3 describes a method for producing 3-cyclopropyl-2,3-epoxypropionic acid ester by synthesizing it from cyclopropanecarbaldehyde, followed by alkaline hydrolysis and acid treatment. On the other hand, Non-Patent Documents 1 and 2 describe methods for synthesizing the corresponding aldehydes using certain acetylene compounds and a ruthenium catalyst.

[0003] On the other hand, Patent Documents 4 and 5 describe benzoxazole compounds useful as pesticides and cyclopropylpyridine compounds as synthetic intermediates thereof. [Prior art documents] [Patent Documents]

[0004] [Patent Document 1] No. CN109705154 [Patent Document 2] No. CN109111333 [Patent Document 3] International Publication 2003 / 042145 Pamphlet [Patent Document 4] International Publication 2019 / 009387 Brochure [Patent Document 5] Japanese Patent Publication No. 2020-172469 [Non-patent literature]

[0005] [Non-Patent Document 1] Angew.Chem.Int.Ed. 2014, 53, 7892-7895 [Non-Patent Document 2] Journal of the Society of Synthetic Organic Science, 58(6), 2000, 587-596 [Overview of the project] [Problems that the invention aims to solve]

[0006] The object of the present invention is to provide a method for producing cyclopropylacetaldehyde, which can be used in the production of cyclopropylpyridine compounds, which are synthetic intermediates for benzoxazole compounds useful as pesticides. [Means for solving the problem]

[0007] The inventors of this application conducted extensive research to solve the aforementioned problems and, as a result, discovered a method for producing cyclopropylacetaldehyde in high yield and industrially advantageous terms, thus completing the present invention.

[0008] In other words, the present invention is [1] The present invention relates to a method for producing cyclopropylacetaldehyde, characterized by reacting cyclopropylacetylene with water in a solvent in the presence of a ruthenium catalyst and a ligand. [Effects of the Invention]

[0009] According to the present invention, the target compound can be produced efficiently and economically on an industrial scale. [Best Mode for Carrying Out the Invention]

[0010] The present invention is a method for producing cyclopropylacetaldehyde, characterized by reacting cyclopropylacetylene with water in a solvent in the presence of a ruthenium catalyst and a ligand.

[0011] Examples of ruthenium catalysts that can be used in this reaction include ruthenium(III) chloride, (η) 5 -Cyclopentadienyl)tris(acetonitrile)ruthenium hexafluorophosphate:[CpRu(CH3CN)3]PF6,(η 5 -cyclopentadienyl)(η 6 -Naphthalene)Ruthenium hexafluorophosphate:CpRu(C 10 H8)]PF6, (η 5 Examples of ruthenium complexes include, but are not limited to, cyclopentadienyl tris(acetonitrile)ruthenium trifluorosulfonate:[CpRu(CH3CN)3]OTf.

[0012] The amount of ruthenium catalyst used in this reaction can be appropriately selected from the range of 0.5 molar equivalents to 0.0001 molar equivalents per mole of cyclopropylacetylene.

[0013] Ligands that can be used in this reaction include, for example, monodentate ligands such as tri-t-butylphosphine, tricyclohexylphosphine, triphenylphosphine, tri-o-tolylphosphine, diphenyl(pentafluorophenyl)phosphine, isoquinolone-3-yldiphenylphosphine, 6-pivaloylamino-2-pyridyldiphenylphosphine, methyldiphenylphosphine, dimethylphenylphosphine, trimethylphosphine, or 2,2'-bipyridine, 5-bromo-2,2'-bipyridine, and 6-bromo-2,2'-bipyridine. 5,5-dibromo-2,2'-bipyridine, 5,5-difluoro-2,2'-bipyridine, 6,6-difluoro-2,2'-bipyridine, 4,4-dimethyl-2,2'-bipyridine, 4,4-diphenyl-2,2'-bipyridine, 4,4-dimethoxy-2,2'-bipyridine, [2,2'-bipyridine]-3,3'-dicarboxylic acid, [2,2'-bipyridine]-5,5'-dicarboxylic acid, dimethyl[2,2'-bipyridine]-4,4'-dicarboxylate, 4,4'-bis(trifluoromethyl)-2,2'-bipyridine, 5,5'-bis (Trifluoromethyl)-2,2'-bipyridine, 1,10-phenanthroline, 1,10-phenanthroline-5,6-dione, 2,9-dimethyl-1,10-phenanthroline, 5-chloro-1,10-phenanthroline, 3,3-dibromo-1,10-phenanthroline, 5,6-dibromo-1,10-phenanthroline, 3,5,6,8-tetrabromo-1,10-phenanthroline, 2-(diphenylphosphino)-6-(2,4,6-triisopropylphenyl)pyridine, 2-(tert-butyl)-6-(2,6-di Phenylphosphino)pyridine, 2-(tert-butyl)-2-(diphenylphosphino)-1-methyl-1H-imidazole, 1,1-bisdiphenylphosphinomethane (dppm), 1,2-bisdiphenylphosphinoethane (dppe), 1,3-bisdiphenylphosphinopropane (dppp), 1,4-bisdiphenylphosphinotane (dppb), bis[2-(diphenylphosphino)phenyl]ether (DPEphos), 1,2-bis(diphenylphosphino)benzene, bis(dimethylphosphino)methane, 1,Examples of bidentate ligands include, but are not limited to, 2-bis(dimethylphosphino)ethane and the like.

[0014] The amount of the ligand used in this reaction can be appropriately selected from the range of 0.5 molar equivalent to 0.0001 molar equivalent with respect to 1 mole of cyclopropylacetylene.

[0015] In this reaction, the ruthenium catalyst and the ligand may be added to the reaction system separately, or a catalyst may be prepared in advance from the ruthenium catalyst and the ligand and added to the reaction system. Examples of such catalysts include, but are not limited to, (5,5'-bis(trifluoromethyl)-2,2'-bipyridine)-chloro-(η 5 -cyclopentadienyl)ruthenium, (1,1-bis(diphenylphosphinomethane)-chloro-(η 5 -cyclopentadienyl)ruthenium: RuCpCl(dppm) and the like.

[0016] The water that can be used in this reaction may be any water that does not significantly inhibit this reaction. Examples include industrial water, tap water, ion-exchanged water, pure water, etc., and ion-exchanged water and pure water are preferred.

[0017] Since this reaction is an equimolar reaction, 1 molar equivalent of water may be used with respect to 1 mole of cyclopropylacetylene, but an excess amount can also be used. The amount used can range from 1 molar equivalent to the amount of the solvent.

[0018] Any inert solvent that does not significantly inhibit the reaction can be used in this reaction. Examples include linear or cyclic ethers such as diethyl ether, tetrahydrofuran (THF), and dioxane; linear or cyclic saturated hydrocarbons such as pentane, hexane, and cyclohexane; aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated aromatic hydrocarbons such as chlorobenzene and dichlorobenzene; halogenated hydrocarbons such as methylene chloride, chloroform, and carbon tetrachloride; nitriles such as acetonitrile; esters such as ethyl acetate; polar solvents such as N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMA), N-methylpyrrolidone (NMP), and 1,3-dimethyl-2-imidazolidinone (DMI); alcohols such as methanol, ethanol, 1-propanol, and 2-propanol; and water. These inert solvents can be used individually or in any ratio of two or more.

[0019] Although this reaction can be carried out in the atmosphere, it is preferable to carry it out under an inert gas such as nitrogen gas or argon gas, as it is a catalytic reaction.

[0020] The reaction temperature for this reaction can usually be within the range of approximately 0°C to the reflux temperature of the inert solvent used. The reaction time varies depending on the scale of the reaction, the reaction temperature, etc., and is not constant, but can be appropriately selected within the range of a few minutes to 48 hours. After the reaction is complete, the target product can be isolated from the reaction system containing the target product by conventional methods, and if necessary, the target product can be produced by purification by distillation, recrystallization, column chromatography, etc. Alternatively, it can be used in the next reaction without isolation. [Examples]

[0021] The following are examples of typical embodiments of the present invention, but the present invention is not limited to these.

[0022] Example 1. Production of cyclopropylacetaldehyde [ka] Cyclopropylacetylene (264 mg, 4.00 mmol) was dissolved in 2-propanol (10 mL) and water (3 mL) under an argon atmosphere, and RuCpCl (d ppm) (234 g, 0.400 mmol) was added and the mixture was reacted at 100°C for 19 hours. Mesitylene was added as an internal standard, and analysis by NMR revealed a yield of 61% for cyclopropylacetaldehyde. 1 H-NMR (CDCl3, TMS) δ: 9. 9 0 - 9. 7 0(1H, m), 2. 3 3 - 2. 2 5 ( 2 H, m), 1. 1 5 - 0. 9 5 (1 H, m), 0. 65 - 0. 58 (2H, m), 0. 2 1 - 0. 1 5 (2H, m)

[0023] Example 2. Production of cyclopropylacetaldehyde Cyclopropylacetylene (76 mg, 1.15 mmol) was dissolved in DMA (4.6 ml) and water (1.1 ml) under an argon atmosphere. [CpRu(CH3CN)3]PF6 (100 mg, 0.230 mmol) and 5,5'-bis(trifluoromethyl)-2,2'-bipyridyl (67 mg, 0.230 mmol) were added, and the mixture was stirred at 45°C for 7 hours. Mesitylene was added as an internal standard, and analysis by NMR revealed a yield of 57% for cyclopropylacetaldehyde.

[0024] Example 3. Production of cyclopropylacetaldehyde Cyclopropylacetylene (76 mg, 1.15 mmol) was dissolved in DMA (4.6 mL) and water (1.1 mL) under an argon atmosphere. [CpRu(CH3CN)3]PF6 (100 mg, 0.230 mmol) and [2,2'-bipyridine]-5,5'-dicarboxylic acid (56 mg, 0.230 mmol) were added, and the mixture was stirred at 45°C for 7 hours. Mesitylene was added as the internal standard, and analysis by NMR revealed a yield of 57% for cyclopropylacetaldehyde.

[0025] Example 4. Production of cyclopropylacetaldehyde Under an argon atmosphere, [CpRu(CH3CN)3]OTf (43.9 mg, 0.100 mmol), 5,5'-bis(trifluoromethyl)-2,2'-bipyridine (29.2 mg, 0.100 mmol), NMP (4 mL), and water (1 mL) were sequentially added, and the mixture was stirred at 60 °C for 3 hours. After confirming that the solution had turned purple, it was cooled to room temperature, and cyclopropylacetylene (66.1 mg, 1.00 mmol) was added, followed by stirring for 24 hours. Mesitylene was added as an internal standard substance, and the analysis using NMR showed that the yield of cyclopropylacetaldehyde was 56%.

[0026] Reference Example 1. Production of (E)-4-cyclopropyl-2-(ethanesulfonyl)but-2-enenitrile

Chemical formula

[0027] Reference Example 2. Production of (2E)-4-cyclopropyl-5-(dimethylamino)-2-(ethanesulfonyl)penta-2,4-dienenitrile

Chemical formula

[0028] Reference Example 3. Production of 2-chloro-5-cyclopropyl-3-(ethanesulfonyl)pyridine [ka] To 80 mL of ethyl acetate solution of hydrogen chloride (4 mol / L), (2E)-4-cyclopropyl-5-(dimethylamino)-2-(ethanesulfonyl)penta-2,4-diennitrile (1.3 g, 5.0 mmol) was gradually added under stirring, and the mixture was stirred at room temperature for 24 hours. After cooling, water was added to the reaction mixture, and it was extracted with ethyl acetate. The organic layer was washed in the following order with water, saturated sodium bicarbonate aqueous solution, and saturated brine, and dried over anhydrous magnesium sulfate. After removing the solvent under reduced pressure, the residue was purified by silica gel column chromatography (ethyl acetate:hexane = 1:2) to obtain the compound described in the title (4.2 g, 17 mmol). Melting point: 60℃

[0029] Reference Example 4. Preparation of 2-(3-ethylsulfonyl-5-cyclopropylpyridine-2-yl)-5-trifluoromethylsulfinylbenzoxazole [ka] A mixture of 5-trifluoromethylsulfinylbenzoxazole (107.6 mg, 0.46 mmol), 2-chloro-5-cyclopropyl-3-ethylsulfonylpyridine (73.5 mg, 0.30 mmol), potassium carbonate (110.9 mg, 0.60 mmol), palladium acetate (3.9 mg, 0.02 mmol), 2,2'-bis(di-p-tolylphosphin)-1,1'-binaphthyl (22.1 mg, 0.03 mmol), and N,N-dimethylacetamide (1.2 mL) was stirred at 100°C for 4 hours. The reaction mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and the organic layer was dried over anhydrous sodium sulfate. After drying, the residue obtained by concentration under reduced pressure was purified by silica gel column chromatography to obtain the title compound (123.3 mg). Yield: 93% 1 NMR(CDCl3,TMS)δ:8.78(1H,d),8.33(1H,s),8.13(1H,d),7.92-7.85(2H,m),4. 02(2H,q),2.17-2.10(1H,m),1.43(3H,t),1.33-1.28(2H,m),1.00-0.96(2H,m)

[0030] Reference Example 5. Production of 2-(3-ethylsulfonyl-5-cyclopropylpyridine-2-yl)-5-trifluoromethylsulfonylbenzoxazole [ka] A mixture of 5-trifluoromethylsulfonylbenzoxazole (114.4 mg, 0.46 mmol), 2-chloro-5-cyclopropyl-3-ethylsulfonylpyridine (73.6 mg, 0.30 mmol), potassium carbonate (82.9 mg, 0.60 mmol), palladium acetate (3.8 mg, 0.02 mmol), 2,2'-bis(di-p-tolylphosphin)-1,1'-binaphthyl (20.6 mg, 0.03 mmol), and N,N-dimethylacetamide (1.2 mL) was stirred at 100°C for 4 hours. The reaction mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and the organic layer was dried over anhydrous sodium sulfate. After drying, the residue obtained by concentration under reduced pressure was purified by silica gel column chromatography to obtain the title compound (65.6 mg). Yield: 48% Physical properties: 1 HNMR(CDCl3,TMS) δ:8.78(1H,d),8.56(1H,d),8.16-8.13(2H,m),7.94(1H,d),3.99(2H,q ),2.17-2.11(1H,m),1.44(3H,t),1.34-1.29(2H,m),1.01-0.97(2H,m) [Industrial applicability]

[0031] According to the present invention, cyclopropyl aldehyde can be produced industrially advantageously.

Claims

[Claim 1] A method for producing cyclopropylacetaldehyde, characterized by reacting cyclopropylacetylene with water in a solvent in the presence of a ruthenium catalyst and a ligand.

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