Process for ruthenium-catalysed hydrogenation of aldehyde acetals

Abstract

To provide a process for the ruthenium-catalysed hydrogenation of aldehyde acetals that can achieve a high yield.SOLUTION: A process includes the following steps: a) charging an aldehyde acetal; b) adding an Ru compound capable of forming a complex and a ligand containing a P atom, or an Ru-ligand complex in which a ligand of the complex contains a P atom; c) supplying H2; and d) heating a reaction mixture from the steps a) to c) and converting the aldehyde acetal into an alcohol compound.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a ruthenium-catalyzed hydrogenation method of aldehyde acetal.

Background Art

[0002] German Patent Application Publication No. 4220939 describes a method for producing 2-aryl-ethanol.

[0003]

Chemical formula

[0004] This reaction is carried out in a sulfuric acid medium and is catalyzed by a Ru / C catalyst, that is, a supported Ru catalyst with carbon powder as a support.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0006] The present invention is based on the object of providing a ruthenium-catalyzed hydrogenation method of aldehyde acetal that can achieve a good yield.

Means for Solving the Problems

[0007] This object is achieved by the method according to claim 1. a) First, formulas (Ia) to (VIa):

[0008]

Chemical formula

[0009] (wherein a, c, d, f are integers from 0 to 12, b, e are integers from 1 to 12, and R 1 , R 2 , R 3 , R 4 are each independently (C1-C 12 )-alkyl.) A step of introducing any one of the aldehyde acetals of b) A step of adding a Ru compound capable of forming a complex and a ligand containing a P atom, or a Ru ligand complex in which the ligand of the complex contains a P atom, c) A step of supplying H2, d) Heating the reaction mixture of the above step a) to the above step c), and converting the aldehyde acetal into compounds of formula (Ib) to formula (VIb):

[0010]

Chemical formula

[0011] The step of conversion A method comprising

[0012] The expression (C1-C 12 )-alkyl includes linear and branched alkyl groups having 1 to 12 carbon atoms. These are preferably (C1-C8)-alkyl, more preferably (C1-C6)-alkyl, and most preferably (C1-C4)-alkyl.

[0013] In one variant of this method, R 1 , R 2 are the same radical.

[0014] In one variant of this method, R 3 , R 4 are the same radical.

[0015] In one variant of this method, R 1 , R 2 , R 3 , R 4 are the same radical.

[0016] In one modification of this method, R 1 , R 2 , R 3 , R 4 is (C1-C4)-alkyl.

[0017] In one modification of this method, the Ru compound is selected from RuCl3×3H2O, [Ru(cymene)Cl2]2, RuBr3×3H2O, RuI3, Ru(PPh3)3Cl2.

[0018] In one modification of this method, the ligand is a phosphine ligand or a phosphite ligand.

[0019] In one modification of this method, the ligand is a phosphine ligand.

[0020] In one modification of this method, 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).

[0021] In one modification of this method, H2 is supplied at a pressure in the range of 0.5 MPa (5 bar) to 8 MPa (80 bar).

[0022] In one modification of this method, H2 is supplied at a pressure in the range of 1 MPa (10 bar) to 6 MPa (60 bar).

[0023] In one modification of this method, the reaction mixture is heated to a temperature in the range of 30 °C to 100 °C.

[0024] In one modification of this method, the reaction mixture is heated to a temperature in the range of 40 °C to 80 °C.

[0025] In a modified example of this method, the method includes an additional step of adding a solvent in c’).

[0026] In a modified example of this method, the solvent is selected from 1,4 - dioxane, tetrahydrofuran (THF), and water.

[0027] Hereinafter, the present invention will be described in more detail with reference to examples.

Example

[0028] General (Autoclave) An appropriate amount of RuCl3×3H2O, PPh3, and a magnetic stirrer were placed in an 8 mL volumetric vial. Then, the vial was sealed with a septum (silicone rubber coated with PTFE) and a phenolic resin cap. The vial was connected to an argon supply line via a needle. The vial was evacuated three times and filled with argon. When an ether solvent (THF or 1,4 - dioxane, stored under argon), an appropriate amount of water, and a substrate were injected into the vial with a syringe, a dark - colored solution was formed. The vial was placed in a stainless - steel plate, and the needle was left as it was so that gas exchange could occur in the autoclave. The plate was placed in a Parr Instruments model 4760 series autoclave (300 mL capacity) under an argon atmosphere. The autoclave was purged three times with hydrogen, and then the hydrogen pressure was raised to 20 bar / 40 bar at room temperature. The autoclave was heated at 60 °C (temperature of the aluminum block) for 18 hours on a heating / stirring device equipped with a magnetic stirrer to carry out the reaction. When the reaction time ended, the autoclave was cooled to room temperature, and the pressure was carefully released. Then, tetradecane (0.100 mL) was injected as an internal standard. A) From 1,1 - dimethoxynonane to 1 - nonanol

[0029]

Chemical formula

[0030] THF (1.5 mL), 0.135 mL of water (7.5 mmol), and 0.55 mL of 1,1-dimethoxynonane (0.47 g, 2.5 mmol) were added to 1.3 mg of RuCl3·3H2O (0.2 mol%) and 5.2 mg of PPh3 (0.8 mol%). H2 was injected up to 20 bar, and the reaction was carried out at 60 °C for 18 hours. The yield (GC) was quantitative.

[0031] Variation of ligands 1,4-Bis(diphenylphosphino)butane (dppb): 1.5 mL of dioxane (anhydrous), 0.36 mL of water (15 mmol), and 0.55 mL of 1,1-dimethoxynonane (0.47 g, 2.5 mmol) were added to 2.6 mg of RuCl3·3H2O (0.4 mol%) and 8.5 mg of 1,4-bis(diphenylphosphino)butane (0.04 mmol, 0.8 mol%). H2 was injected up to 20 bar, and the reaction was carried out at 60 °C for 18 hours. The yield (GC) was quantitative.

[0032] 1,1'-Ferrocenediylbis(diphenylphosphine) (dppf): 1.5 mL of dioxane (anhydrous), 0.36 mL of water (15 mmol), and 0.55 mL of 1,1-dimethoxynonane (0.47 g, 2.5 mmol) were added to 2.6 mg of RuCl3·3H2O (0.4 mol%) and 11.1 mg of 1,1'-ferrocenediylbis(diphenylphosphine) (0.04 mmol, 0.8 mol%). H2 was injected up to 20 bar, and the reaction was carried out at 60 °C for 18 hours. The yield (GC) was quantitative.

[0033] Bis[2-(diphenylphosphino)phenyl]ether (dpephos): 1,4-Dioxane (1.5 mL, anhydrous), 0.36 mL (15 mmol) of water, and 0.55 mL (0.47 g, 2.5 mmol) of 1,1-dimethoxynonane were 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 was injected up to 20 bar, and the reaction was carried out at 60 °C for 18 hours. The yield (GC) was quantitative.

[0034] 1,3-Bis(diphenylphosphino)propane (dppp): 1,4-Dioxane (1.5 mL, anhydrous), 0.36 mL (15 mmol) of water, and 0.55 mL (0.47 g, 2.5 mmol) of 1,1-dimethoxynonane were 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 was injected up to 20 bar, and the reaction was carried out at 60 °C for 18 hours. The yield (GC) was quantitative.

[0035] 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (XantPhos): 1,4-Dioxane (1.5 mL, anhydrous), 0.36 mL (15 mmol) of water, and 0.55 mL (0.47 g, 2.5 mmol) of 1,1-dimethoxynonane were 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 was injected up to 20 bar, and the reaction was carried out at 60 °C for 18 hours. Yield (GC): 59%.

[0036] Variations of Ru compounds [Ru(cymene)Cl2]2: 1,4-Dioxane (1.5 mL, anhydrous), 0.36 mL (15 mmol) of water, and 0.55 mL (0.47 g, 2.5 mmol) of 1,1-dimethoxynonane were added to 3.1 mg of [Ru(cymene)Cl2]2 (ruthenium 0.4 mol%) and 10.5 mg of PPh3 (0.04 mmol, 1.6 mol%). H2 was injected up to 20 bar, and the reaction was carried out at 60 °C for 18 hours. The yield (GC) was quantitative.

[0037] RuBr3·3H2O: 1,4-Dioxane (1.5 mL, anhydrous), 0.36 mL (15 mmol) of water, and 0.55 mL (0.47 g, 2.5 mmol) of 1,1-dimethoxynonane were added to 3.9 mg of RuBr3·3H2O (ruthenium 0.4 mol%) and 10.5 mg of PPh3 (0.04 mmol, 1.6 mol%). H2 was injected up to 20 bar, and the reaction was carried out at 60 °C for 18 hours. Yield (GC): 93%.

[0038] RuI3: 1,4-Dioxane (1.5 mL, anhydrous), 0.36 mL (15 mmol) of water, and 0.55 mL (0.47 g, 2.5 mmol) of 1,1-dimethoxynonane were added to 4.8 mg of RuI3 (ruthenium 0.4 mol%) and 10.5 mg of PPh3 (0.04 mmol, 1.6 mol%). H2 was injected up to 20 bar, and the reaction was carried out at 60 °C for 18 hours. Yield (GC): 75%.

[0039] Ru(PPh3)3Cl2: 1,4-Dioxane (1.5 mL, anhydrous), 0.36 mL (15 mmol) of water, and 0.55 mL (0.47 g, 2.5 mmol) of 1,1-dimethoxynonane were added to 9.6 mg of Ru(PPh3)3Cl2 (ruthenium 0.4 mol%) and 2.6 mg of PPh3 (0.01 mmol, 0.4 mol%). H2 was injected up to 20 bar, and the reaction was carried out at 60 °C for 18 hours. The yield (GC) was quantitative.

[0040] Variations of aldehyde acetals

[0041] B) From 1,1,6,6 - tetramethoxyhexane to hexane - 1,6 - diol

[0042] [Chemical formula]

[0043] 1,4 - Dioxane (6 mL, anhydrous), 1.44 mL of water (80 mmol), 2.06 g of 1,1,6,6 - tetramethoxyhexane (10 mmol), 10.5 mg of RuCl3·3H2O (0.4 mol %), and 42 mg of PPh3 (1.6 mol %) were added to a vial. H2 was injected up to 40 bar, and the reaction was carried out at 60 °C for 18 hours. The GC yield was 81%.

[0044] C) From 1,1,6,6 - tetrabutoxyhexane to hexane - 1,6 - diol

[0045] [Chemical formula]

[0046] 1.5 mL of THF, 0.99 g of 1,1,6,6 - tetrabutoxyhexane (2.64 mmol), 0.72 mL of H2O, 2.6 mg of RuCl3·3H2O (0.38 mol %), and 10.5 mg of PPh3 (1.52 mol %) were added to a vial. H2 was injected up to 20 bar, and the reaction was carried out at 60 °C for 18 hours. The GC yield was 90%.

[0047] D) From 1,1,4,4 - tetramethoxybutane to butane - 1,4 - diol

[0048] [Chemical formula]

[0049] 1.5 mL of dioxane, 0.54 mL of water, 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 were added to a vial. H2 was injected up to 20 bar, and the reaction was carried out at 60 °C for 18 hours. The NMR yield was 66%.

[0050] E) From benzaldehyde dimethyl acetal to benzyl alcohol

[0051]

Chemical formula

[0052] 1.5 mL of THF, 0.135 g of H2O, 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 were added to a vial. H2 was injected up to 20 bar, and the reaction was carried out at 60 °C for 18 hours. The GC yield was more than 99%.

[0053] F) From phenylacetaldehyde dimethyl acetal to 2 - phenylethanol

[0054]

Chemical formula

[0055] 1.5 mL of dioxane, 0.36 g of H2O, 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 were added to a vial. H2 was injected up to 20 bar, and the reaction was carried out at 60 °C for 18 hours. The GC yield was more than 99%.

[0056] G) From 4 - methyl - 2 - octyl - 1,3 - dioxolane to 1 - nonanol

[0057]

Chem.

[0058] 1,4 - Dioxane (1.5 mL, anhydrous), 0.135 mL (7.5 mmol) of water, 0.5 mL (0.47 g, 2.3 mmol) of 4 - methyl - 2 - octyl - 1,3 - dioxolane, 2.6 mg (0.4 mol%) of RuCl3·3H2O, and 10.5 mg (1.6 mol%) of PPh3 were added to a vial. H2 was injected up to 40 bar, and the reaction was carried out at 60 °C for 18 hours. The GC yield was 89%.

[0059] H) From 2,5 - dimethoxytetrahydrofuran (cis / trans mixture) to butane - 1,4 - diol

[0060]

Chem.

[0061] 1.5 mL of dioxane, 0.18 mL of water, 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 were added to a vial. H2 was injected up to 20 bar, and the reaction was carried out at 60 °C for 18 hours. The GC yield was 84%.

[0062] I) From 3 - ethoxypropionaldehyde diethyl acetal to 3 - ethoxypropanol

[0063]

Chem.

[0064] 1.5 mL of dioxane, 0.27 g of H2O, 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 were added to a vial. H2 was injected up to 20 bar, and the reaction was carried out at 60 °C for 18 hours. The GC yield was more than 99%.

[0065] Variations of the catalyst system

[0066] J) From phenylacetaldehyde dimethyl acetal to 2-phenylethanol

[0067]

Chemical formula

[0068] The solid catalyst was weighed into an 8 mL volumetric vial, and all the liquids were added with a syringe. Finally, the substrate was added.

[0069] The following catalyst systems were tested: Catalyst 1: 0.4 mol% of RuCl3×3H2O, 1.6 mol% of PPh3, 0.36 mL of water, 1.5 mL of dioxane Catalyst 2: Ru / C 5% (Strem) 44 - 4065 LOT#: 21539500, moisture content 50%, metal 0.67 mol%, calculated with 0.17 mL of 0.1 M H2SO4 (aqueous solution), 1.34 mL of water, 1.5 mL of methanol Catalyst 3: Ru / C 5% (Johnson - Matthey) type 622, LOT KS0004, 0.17 mL of 0.1 M H2SO4 (aqueous solution), 1.34 mL of water, 1.5 mL of methanol

[0070] After the reaction, diglyme was added as a GC standard. Reaction conditions: Substrate 2.5 mmol, H2: 20 bar, 60 °C, 5 hours. The experimental results are shown in the following table.

[0071]

Table 1

[0072] As shown by the experimental results, this object is achieved by the method of the present invention.

Claims

1. a) First, a step of introducing any one of the aldehyde acetals of formula (Ia) to formula (Via): 【Chemical 1】 (wherein a, c, d, and f are integers from 0 to 12, b and e are integers from 1 to 12, and R １ , R ２ , R ３ , R ４ are each independently (C １ -C １２ )-alkyl.) b) A step of adding an Ru compound capable of forming a complex and a ligand containing a P atom, or an Ru ligand complex in which the ligand of the complex contains a P atom d) Heating the reaction mixture of the above steps a) to c), and converting the aldehyde acetal into a compound of formula (Ib) to formula (Vib): c) Supplying H ２ and The step of conversion [Chemical Formula 2] A method comprising the steps of

2.

3. R １ and R ２ are the same group, the method according to claim 1.

4. R ３ and R ４ are the same group, the method according to claim 1 or claim 2.

5. R １ 、R ２ 、R ３ 、R ４ is (C １ -C ４ )-alkyl, the method according to any one of claims 1 to 3.

6. The Ru compound is RuCl ３ ×3H ２ O, [Ru(cymene)Cl ２ ２ , RuBr ３ ×3H ２ O, RuI ３ , Ru(PPh ３ ) ３ Cl ２ The method according to any one of claims 1 to 4, selected from​​​ The method according to any one of claims 1 to 5, wherein the ligand is a phosphine ligand

7.

8. The ligand is PPh ３ , 1,4-bis(diphenylphosphino)butane (dppb), 1,1'-ferrocenediylbis(diphenylphosphine) (dppf), bis[2-(diphenylphosphino)phenyl]ether (dpephos), 1,3-bis(diphenylphosphino)propane (dpppp), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (XantPhos), and the method according to any one of claims 1 to 6.

9. H ２ The method according to any one of claims 1 to 7, wherein H is supplied at a pressure in the range of 0.5 MPa (5 bar) to 8 MPa (80 bar). The method according to any one of claims 1 to 8, wherein the reaction mixture is heated to a temperature in the range of 30 °C to 100 °C

10. The method according to any one of claims 1 to 9, further comprising an additional step c') of adding a solvent

11. The method according to claim 10, wherein the solvent is selected from 1,4-dioxane, tetrahydrofuran (THF), and water ​

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