Process for hydrogenation of acetals by ruthenium catalysis

Abstract

The invention relates to a method for hydrogenating acetals by ruthenium catalysis.

Description

Technical Field

[0001] The present invention relates to a method for hydrogenating acetals by ruthenium catalysis. Background Art

[0002] DE 4220939A1 describes a method for preparing 2-aryl ethanol:

[0003]

[0004] The reaction is carried out in a sulfuric acid medium and catalyzed by a Ru / C catalyst, i.e., a Ru-supported catalyst with carbon powder as the carrier. Summary of the Invention

[0005] The object of the present invention is to provide a method for hydrogenating acetals by ruthenium catalysis, which can achieve good yields.

[0006] This object is achieved by the method according to claim 1.

[0007] A method comprising the following method steps:

[0008] a) Preloading an acetal according to one of formulas (Ia) to (VIa):

[0009]

[0010] where a, c, d, f are integers from 0 to 12, and b, e are integers from 1 to 12, and R 1 , R 2 , R 3 , R 4 are each independently of one another (C1-C 12 )-alkyl;

[0011] b) Adding a Ru compound capable of forming a complex and a ligand containing a P atom, or

[0012] a Ru-ligand complex, wherein the ligand of the complex contains a P atom;

[0013] c) Feeding in H2;

[0014] d) Heating the reaction mixture from a) to c), thereby converting the acetal into a compound according to formulas (Ib) to (VIb):

[0015]

[0016] The term (C1-C 12 )-alkyl includes straight-chain and branched alkyls having 1 to 12 carbon atoms. These are preferably (C1-C8)-alkyls, more preferably (C1-C6)-alkyls, and most preferably (C1-C4)-alkyls.

[0017] In a variant of the method, R 1 , R 2 are the same group.

[0018] In a variant of the method, R 3 , R 4 are the same group.

[0019] In a variant of the method, R 1 , R 2 , R 3 , R 4 are the same group.

[0020] In a variant of the method, R 1 , R 2 , R 3 , R 4 are (C1-C4)-alkyl.

[0021] In a variant of the method, the Ru compound is selected from: RuCl3 x 3H2O, [Ru(cumene)Cl2]2, RuBr3 x 3H2O, RuI3, Ru(PPh3)3Cl2.

[0022] In a variant of the method, the ligand is a phosphine ligand or a phosphite ligand.

[0023] In a variant of the method, the ligand is a phosphine ligand.

[0024] In a variant of the 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).

[0025] In a variant of the method, the introduction of H2 is carried out under a pressure of 0.5 MPa (5 bar) to 8 MPa (80 bar).

[0026] In a variant of the method, the introduction of H2 is carried out under a pressure of 1 MPa (10 bar) to 6 MPa (60 bar).

[0027] In a variant of the method, the reaction mixture is heated to a temperature of 30 °C to 100 °C.

[0028] In a variant of the method, the reaction mixture is heated to a temperature of 40 °C to 80 °C.

[0029] In a variant of the method, the method includes an additional method step c'):

[0030] c') adding a solvent.

[0031] In a variant of the method, the solvent is selected from: 1,4-dioxane, tetrahydrofuran (THF), water.

[0032] The present invention will be described in more detail below with reference to the examples. Specific embodiments

[0033] Experimental description

[0034] General (autoclave)

[0035] An 8 ml vial was charged with the appropriate amounts of RuCl3 x 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 an argon line through a needle. The vial was evacuated and flushed 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, thereby forming a dark solution.

[0036] The vial was placed in a stainless steel plate with the needle still in place to enable gas exchange in the autoclave. The plate was transferred under an argon atmosphere to a Parr Instruments 4760 series autoclave (300 ml). After the autoclave was purged with hydrogen three times, the hydrogen pressure was raised to 20 bar / 40 bar at room temperature. The reaction was carried out by heating the autoclave in an aluminum block on a heating / stirring device with a magnetic stirrer at 60 °C (aluminum block temperature) for 18 hours. After 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.

[0037] A) Conversion of 1,1-dimethoxynonane to 1-nonanol

[0038]

[0039] THF (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 x 3H2O and 5.2 mg (0.8 mol%) of PPh3. 20 bar of H2 was injected and the reaction was carried out at 60 °C for 18 hours. The yield (GC) was quantified.

[0040] Variation of the ligand

[0041] 1,4-Bis(diphenylphosphino)butane (dppb):

[0042] Add 1.5 ml (anhydrous) of dioxane, 0.36 ml (15 mmol) of water, and 0.55 ml (0.47 g, 2.5 mmol) of 1,1-dimethoxynonane 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. Inject 20 bar of H2, and the reaction is carried out at 60 °C for 18 hours. The yield (GC) is quantified.

[0043] 1,1'-Ferrocenediylbis(diphenylphosphine) (dppf):

[0044] Add 1.5 ml (anhydrous) of dioxane, 0.36 ml (15 mmol) of water, and 0.55 ml (0.47 g, 2.5 mmol) of 1,1-dimethoxynonane 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). Inject 20 bar of H2, and the reaction is carried out at 60 °C for 18 hours. The yield (GC) is quantified.

[0045] Bis[2-(diphenylphosphino)phenyl]ether (dpephos):

[0046] Add 1.5 ml (anhydrous) of dioxane, 0.36 ml (15 mmol) of water, and 0.55 ml (0.47 g, 2.5 mmol) of 1,1-dimethoxynonane 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. Inject 20 bar of H2, and the reaction is carried out at 60 °C for 18 hours. The yield (GC) is quantified.

[0047] 1,3-Bis(diphenylphosphino)propane (dppp):

[0048] Add 1.5 ml (anhydrous) of dioxane, 0.36 ml (15 mmol) of water, and 0.55 ml (0.47 g, 2.5 mmol) of 1,1-dimethoxynonane 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. Inject 20 bar of H2, and the reaction is carried out at 60 °C for 18 hours. The yield (GC) is quantified.

[0049] 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (XantPhos):

[0050] 1,1 - dimethoxynonane (0.55 mL, 0.47 g, 2.5 mmol), dioxane (1.5 mL, anhydrous), and water (0.36 mL, 15 mmol) were added to RuCl3·3H2O (2.6 mg, 0.4 mol%) and 4,5 - bis(diphenylphosphino)-9,9 - dimethylxanthene (11.6 mg, 0.02 mmol, 0.8 mol%). H2 (20 bar) was introduced, and the reaction was carried out at 60 °C for 18 h. Yield (GC): 59%.

[0051] Variation of Ru compounds

[0052] [Ru(cymene)Cl2]2:

[0053] 1,1 - dimethoxynonane (0.55 mL, 0.47 g, 2.5 mmol), dioxane (1.5 mL, anhydrous), and water (0.36 mL, 15 mmol) were added to [Ru(cymene)Cl2]2 (3.1 mg, 0.4 mol% Ru) and PPh3 (10.5 mg, 0.04 mmol, 1.6 mol%). H2 (20 bar) was introduced, and the reaction was carried out at 60 °C for 18 h. Yield (GC): quantitative.

[0054] RuBr3·3H2O:

[0055] 1,1 - dimethoxynonane (0.55 mL, 0.47 g, 2.5 mmol), dioxane (1.5 mL, anhydrous), and water (0.36 mL, 15 mmol) were added to RuBr3·3H2O (3.9 mg, 0.4 mol% Ru) and PPh3 (10.5 mg, 0.04 mmol, 1.6 mol%). H2 (20 bar) was introduced, and the reaction was carried out at 60 °C for 18 h. Yield (GC): 93%.

[0056] RuI3:

[0057] 1,1 - dimethoxynonane (0.55 mL, 0.47 g, 2.5 mmol), dioxane (1.5 mL, anhydrous), and water (0.36 mL, 15 mmol) were added to RuI3 (4.8 mg, 0.4 mol% Ru) and PPh3 (10.5 mg, 0.04 mmol, 1.6 mol%). H2 (20 bar) was introduced, and the reaction was carried out at 60 °C for 18 h. Yield (GC): 75%.

[0058] Ru(PPh3)3Cl2:

[0059] Add 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 to 9.6 mg (0.4 mol% ruthenium) of Ru(PPh3)3Cl2 and 2.6 mg (0.01 mmol, 0.4 mol%) of PPh3. Inject 20 bar of H2 and the reaction is carried out at 60 °C for 18 h. The yield (GC) is quantitative.

[0060] Changes in acetals

[0061] B) Conversion of 1,1,6,6-tetramethoxyhexane to hexane-1,6-diol

[0062]

[0063] Add 1,4-dioxane (6 ml, anhydrous), 1.44 ml (80 mmol) of water, 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 to a vial. Inject 40 bar of H2 and the reaction is carried out at 60 °C for 18 h. The GC yield is 81%.

[0064] C) Conversion of 1,1,6,6-tetrabutoxyhexane to hexane-1,6-diol

[0065]

[0066] Add 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 to a vial. Inject 20 bar of H2 and the reaction is carried out at 60 °C for 18 h. The GC yield is 90%.

[0067] D) Conversion of 1,1,4,4-tetramethoxybutane to butane-1,4-diol

[0068]

[0069] Add 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 to a vial. Inject 20 bar of H2 and the reaction is carried out at 60 °C for 18 h. The NMR yield is 66%.

[0070] E) Conversion of benzaldehyde dimethyl acetal to benzyl alcohol

[0071]

[0072] 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 were added to a vial. 20 bar of H2 was injected, and the reaction was carried out at 60 °C for 18 h. The GC yield was >99%.

[0073] F) Conversion of phenylacetaldehyde dimethyl acetal to 2-phenylethanol

[0074]

[0075] 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·H2O, and 10.5 mg (1.6 mol%) of PPh3 were added to a vial. 20 bar of H2 was injected, and the reaction was carried out at 60 °C for 18 h. The GC yield was >99%.

[0076] G) Conversion of 4-methyl-2-octyl-1,3-dioxolane to 1-nonanol

[0077]

[0078] 1,4-Dioxane (1.5 ml, anhydrous), 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 were added to a vial. 40 bar of H2 was injected, and the reaction was carried out at 60 °C for 18 h. The GC yield was 89%.

[0079] H) Conversion of 2,5-dimethoxytetrahydrofuran (cis / trans mixture) to butane-1,4-diol

[0080]

[0081] 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 were added to a vial. 20 bar of H2 was injected and the reaction was carried out at 60 °C for 18 h. The GC yield was 84%.

[0082] I) Conversion of 3-ethoxypropanal diethyl acetal to 3-ethoxypropanol

[0083]

[0084] 1.5 ml of dioxane, 0.27 g of H2O, 0.451 g (2.56 mmol) of ethoxypropanal 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. 20 bar of H2 was injected and the reaction was carried out at 60 °C for 18 h. The GC yield was >99%.

[0085] Changes in the catalyst system

[0086] J) Conversion of phenylacetaldehyde dimethyl acetal to 2-phenylethanol

[0087]

[0088] The solid catalyst was weighed into an 8 mL vial and all the liquids were added using a syringe. The substrate was added last.

[0089] The following catalyst systems were tested:

[0090] Catalyst 1: 0.4 mol% RuCl3·3H2O, 1.6 mol% PPh3, 0.36 ml of water, 1.5 ml of dioxane

[0091] Catalyst 2: Ru / C 5% (Strem) 44 - 4065 LOT#: 21539500, water content 50%, calculated as 0.67 mol% of metal, 0.17 ml of 0.1 M H2SO4 (aqueous solution), 1.34 ml of water, 1.5 ml of methanol

[0092] 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

[0093] After the reaction, diethylene glycol dimethyl ether was added as a GC standard.

[0094] Reaction conditions:

[0095] 2.5 mmol of substrate, H2 20 bar, 60 °C, 5 hours.

[0096] The experimental results are listed in the following table:

[0097] Catalyst Yield Catalyst 1* >98％ Catalyst 2 52％ Catalyst 3 56％

[0098] *The catalyst system according to the present invention

[0099] As the experimental results show, the object is achieved by the method according to the present invention.

Claims

1. A method comprising the following steps: a) Pre-charging with an acetal according to one of the formulae (Ia) to (VIa): wherein a, c, d, f are integers from 0 to 12, and b, e are integers from 1 to 12, and R 1 , R 2 , R 3 , R 4 Each is independently (C1-C 12 )-alkyl; b) adding a Ru compound capable of forming a complex and a ligand containing a P atom, or a Ru-ligand complex, wherein the ligand of the complex contains a P atom; c) supplying H2; d) heating the reaction mixture from a) to c), thereby converting the acetal into a compound according to formula (Ib) to (VIb):

2. The method according to claim 1, Where R 1 , R 2 are the same group.

3. The method according to any one of claims 1 or 2, Where R 3 , R 4 are the same group.

4. The method according to any one of claims 1 to 3, Where R 1 , R 2 , R 3 , R 4 It is (C1-C4)-alkyl.

5. The method according to any one of claims 1 to 4, The Ru compound is selected from the group consisting of: RuCl3 x 3H2O, [Ru(methyl isopropylbenzene)Cl2]2, RuBr3 x 3H2O, RuI3, and Ru(PPh3)3Cl2.

6. The method according to any one of claims 1 to 5, The ligand is a phosphine ligand.

7. The method according to any one of claims 1 to 6, The ligand is selected from: PPh3, 1,4-bis(diphenylphosphino)butane (dppb), 1,1'-ferrocenebis(diphenylphosphine) (dppf), bis[2-(diphenylphosphino)phenyl]ether (dpephos), 1,3-bis(diphenylphosphino)propane (dppp), and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (XantPhos).

8. The method according to any one of claims 1 to 7, The H2 is fed in at a pressure of 0.5 MPa (5 bar) to 8 MPa (80 bar).

9. The method according to any one of claims 1 to 8, Therein the reaction mixture is heated to a temperature of 30°C to 100°C.

10. The method according to any one of claims 1 to 9, It comprises the additional method step c'): c') Adding solvent.

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

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