The present invention relates to a process for the ruthenium-catalysed hydrogenation of aldehyde acetals.
DE 42 20 939 A1 describes a process for preparing 2-aryl-ethanols:
The reaction is effected in a sulfuric acid medium and is catalysed by an Ru/C catalyst, that is to say a supported Ru catalyst with carbon powder as support.
The present invention was based on the object of providing a process for the ruthenium-catalysed hydrogenation of aldehyde acetals that makes it possible to achieve a good yield.
This object is achieved by a process according to claim 1.
Process comprising the process steps of:
The expression (C1-C12)-alkyl encompasses straight-chain and branched alkyl groups having 1 to 12 carbon atoms. These are preferably (C1-C8)-alkyl groups, more preferably (C1-C6)-alkyl, most preferably (C1-C4)-alkyl.
In one variant of the process, R1, R2 are the same radical.
In one variant of the process, R3, R4 are the same radical.
In one variant of the process, R1, R2, R3, R4 are the same radical.
In one variant of the process, R1, R2, R3, R4 are (C1-C4)-alkyl.
In one variant of the process, the Ru compound is selected from: RuCl3×3H2O, [Ru(cymene)Cl2]2, RuBr3×3H2O, RuI3, Ru(PPh3)3Cl2.
In one variant of the process, the ligand is a phosphine ligand or phosphite ligand.
In one variant of the process, the ligand is a phosphine ligand.
In one variant of the process, the ligand is selected from: PPh3, 1,4-bis(diphenylphosphino)butane (dppb), 1,1′-ferrocenediylbis(diphenylphosphine) (dppf), bis[2-(diphenylphosphino)phenyl]ether (dpephos), 1,3-bis(diphenylphosphino)propane (dppp), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (XantPhos).
In one variant of the process, H2 is fed in with a pressure in the range from 0.5 MPa (5 bar) to 8 MPa (80 bar).
In one variant of the process, H2 is fed in with a pressure in the range from 1 MPa (10 bar) to 6 MPa (60 bar).
In one variant of the process, the reaction mixture is heated to a temperature in the range from 30° C. to 100° C.
In one variant of the process, the reaction mixture is heated to a temperature in the range from 40° C. to 80° C.
In one variant of the process, the process comprises the additional process step c′):
In one variant of the process, the solvent is selected from: 1,4-dioxane, tetrahydrofuran (THF), water.
The invention is to be elucidated in more detail hereinafter with reference to working examples.
An 8 ml vial was filled with the appropriate amounts of RuCl3×3H2O, PPh3 and a magnetic stirrer. The vial was then sealed with a septum (PTFE-coated silicone rubber) and a phenolic resin cap. The vial was connected to the argon feed line via a needle. The vial was evacuated and filled with argon three times. An ether solvent (THF or 1,4-dioxane, stored under argon) and the appropriate amounts of water and substrate were injected into the vial using a syringe, with the result that a dark solution formed. The vial was placed into a stainless steel plate, with the needle still remaining in place in order to enable gas exchange in the autoclave. The plate was placed into an autoclave (300 ml) of the 4760 series from Parr Instruments under an argon atmosphere. After the autoclave had been purged three times with hydrogen, the hydrogen pressure was increased to 20 bar/40 bar at room temperature. The reaction was carried out by heating the autoclave in an aluminium block on a heating/stirring apparatus with magnetic stirring for 18 h at 60° C. (temperature of the aluminium block). At the end of the reaction time, the autoclave was cooled to room temperature and the pressure was cautiously released. Tetradecane (0.100 ml) was then injected as internal standard.
THE (1.5 ml), 0.135 ml (7.5 mmol) of water and 0.55 ml (0.47 g, 2.5 mmol) of 1,1-dimethoxynonane were added to 1.3 mg (0.2 mol %) of RuCl3×3H2O and 5.2 mg (0.8 mol %) of PPh3. H2 is injected to 20 bar and the reaction is carried out at 60° C. for 18 h. Yield (GC) quantitative.
Dioxane (1.5 ml, absolute), 0.36 ml (15 mmol) of water and 0.55 ml (0.47 g, 2.5 mmol) of 1,1-dimethoxynonane are added to 2.6 mg (0.4 mol %) of RuCl3×3H2O and 8.5 mg (0.04 mmol, 0.8 mol %) of 1,4-bis(diphenylphosphino)butane. H2 is injected to 20 bar and the reaction is carried out at 60° C. for 18 h. Yield (GC) quantitative.
Dioxane (1.5 ml, absolute), 0.36 ml (15 mmol) of water and 0.55 ml (0.47 g, 2.5 mmol) of 1,1-dimethoxynonane are added to 2.6 mg (0.4 mol %) of RuCl3×3H2O and 11.1 mg (0.04 mmol, 0.8 mol %) of 1,1′-ferrocenediylbis(diphenylphosphine). H2 is injected to 20 bar and the reaction is carried out at 60° C. for 18 h. Yield (GC) quantitative.
Dioxane (1.5 ml, absolute), 0.36 ml (15 mmol) of water and 0.55 ml (0.47 g, 2.5 mmol) of 1,1-dimethoxynonane are added to 2.6 mg (0.4 mol %) of RuCl3×3H2O and 10.8 mg (0.04 mmol, 0.8 mol %) of bis[2-(diphenylphosphino)phenyl]ether. H2 is injected to 20 bar and the reaction is carried out at 60° C. for 18 h. Yield (GC) quantitative.
Dioxane (1.5 ml, absolute), 0.36 ml (15 mmol) of water and 0.55 ml (0.47 g, 2.5 mmol) of 1,1-dimethoxynonane are added to 2.6 mg (0.4 mol %) of RuCl3×3H2O and 8.2 mg (0.04 mmol, 0.8 mol %) of 1,3-bis(diphenylphosphino)propane. H2 is injected to 20 bar and the reaction is carried out at 60° C. for 18 h. Yield (GC) quantitative.
Dioxane (1.5 ml, absolute), 0.36 ml (15 mmol) of water and 0.55 ml (0.47 g, 2.5 mmol) of 1,1-dimethoxynonane are added to 2.6 mg (0.4 mol %) of RuCl3×3H2O and 11.6 mg (0.02 mmol, 0.8 mol %) of 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene. H2 is injected to 20 bar and the reaction is carried out at 60° C. for 18 h. Yield (GC) 59%.
Dioxane (1.5 ml, absolute), 0.36 ml (15 mmol) of water and 0.55 ml (0.47 g, 2.5 mmol) of 1,1-dimethoxynonane are added to 3.1 mg (0.4 mol % of ruthenium) of [Ru(cymene)Cl2]2 and 10.5 mg (0.04 mmol, 1.6 mol %) of PPh3. H2 is injected to 20 bar and the reaction is carried out at 60° C. for 18 h. Yield (GC) quantitative.
Dioxane (1.5 ml, absolute), 0.36 ml (15 mmol) of water and 0.55 ml (0.47 g, 2.5 mmol) of 1,1-dimethoxynonane are added to 3.9 mg (0.4 mol % of ruthenium) of RuBr3×3H2O and 10.5 mg (0.04 mmol, 1.6 mol %) of PPh3. H2 is injected to 20 bar and the reaction is carried out at 60° C. for 18 h. Yield (GC) 93%.
Dioxane (1.5 ml, absolute), 0.36 ml (15 mmol) of water and 0.55 ml (0.47 g, 2.5 mmol) of 1,1-dimethoxynonane (0.47 g, 2.5 mmol) are added to 4.8 mg (0.4 mol % of ruthenium) of RuI3 and 10.5 mg (0.04 mmol, 1.6 mol %) of PPh3.
H2 is injected to 20 bar and the reaction is carried out at 60° C. for 18 h. Yield (GC) 75%.
Dioxane (1.5 ml, absolute), 0.36 ml (15 mmol) of water and 0.55 ml (0.47 g, 2.5 mmol) of 1,1-dimethoxynonane are added to 9.6 mg (0.4 mol % of ruthenium) of Ru(PPh3)3Cl2 and 2.6 mg (0.01 mmol, 0.4 mol %) of PPh3. H2 is injected to 20 bar and the reaction is carried out at 60° C. for 18 h. Yield (GC) quantitative.
1,4-Dioxane (6 ml, absolute), 1.44 ml (80 mmol) of water and 2.06 g (10 mmol) of 1,1,6,6-tetramethoxyhexane, 10.5 mg (0.4 mol %) of RuCl3×3H2O and 42 mg (1.6 mol %) of PPh3 are added to a vial. H2 is injected to 40 bar and the reaction is carried out at 60° C. for 18 h. The GC yield is 81%.
1.5 ml of THF, 0.99 g (2.64 mmol) of 1,1,6,6-tetrabutoxyhexane and 0.72 ml of H2O, 2.6 mg (0.38 mol %) of RuCl3×3H2O and 10.5 mg (1.52 mol %) of PPh3 are added to a vial. H2 is injected to 20 bar and the reaction is carried out at 60° C. for 18 h. The GC yield is 90%.
1.5 ml of dioxane, 0.54 ml of water and 0.46 g (2.56 mmol) of 1,1,4,4-tetramethoxybutane, 2.6 mg (0.39 mol %) of RuCl3×3H2O and 10.5 mg (1.56 mol %) of PPh3 are added to a vial. H2 is injected to 20 bar and the reaction is carried out at 60° C. for 18 h. The NMR yield is 66%.
1.5 ml of THF, 0.135 g of H2O and 0.42 g (2.72 mmol) of benzaldehyde dimethyl acetal, 1.3 mg (0.18 mol %) of RuCl3×3H2O and 5.2 mg (0.73 mol %) of PPh3 are added to a vial. H2 is injected to 20 bar and the reaction is carried out at 60° C. for 18 h. The GC yield is >99%.
1.5 ml of dioxane, 0.36 g of H2O and 0.42 g (2.5 mmol) of phenylacetaldehyde dimethyl acetal, 2.6 mg (0.4 mol %) of RuCl3×3H2O and 10.5 mg (1.6 mol %) of PPh3 are added to a vial. H2 is injected to 20 bar and the reaction is carried out at 60° C. for 18 h. The GC yield is >99%.
1,4-Dioxane (1.5 ml, absolute), 0.135 ml (7.5 mmol) of water and 0.5 ml of 4-methyl-2-octyl-1,3-dioxolane (0.47 g, 2.3 mmol), 2.6 mg (0.4 mol %) of RuCl3×3H2O and 10.5 mg (1.6 mol %) of PPh3 are added to a vial. H2 is injected to 40 bar and the reaction is carried out at 60° C. for 18 h. The GC yield is 89%.
1.5 ml of dioxane, 0.18 ml of water and 0.33 g (2.5 mmol) of 2,5-dimethoxytetrahydrofuran (cis/trans mixture), 2.6 mg of RuCl3×3H2O and 10.5 mg (1.6 mol %) of PPh3 are added to a vial. H2 is injected to 20 bar and the reaction is carried out at 60° C. for 18 h. The GC yield is 84%.
1.5 ml of dioxane, 0.27 g of H2O and 0.451 g (2.56 mmol) of ethoxypropionaldehyde diethyl acetal, 2.6 mg (0.39 mol %) of RuCl3×3H2O and 10.5 mg (1.56 mol %) of PPh3 are added to a vial. H2 is injected to 20 bar and the reaction is carried out at 60° C. for 18 h. The GC yield is >99%.
The solid catalyst was weighed out in 8 ml vials and all liquids were added with the syringe. The substrate was added last here.
The following catalyst systems were tested:
Diglyme was added, after the reaction, as GC standard.
The experimental results are listed in the following table:
As the experimental results show, the object is achieved by the process according to the invention.
Number | Date | Country | Kind |
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23219604.8 | Dec 2023 | EP | regional |