Process for the ruthenium-catalysed hydrogenation of aldehyde acetals

Abstract

A method for the ruthenium-catalyzed hydrogenation of acetals.

Description

Technical Field

[0001] This invention relates to the ruthenium-catalyzed hydrogenation of acetals. Prior Technology

[0002] DE 42 20 939 A1 describes a method for preparing 2-aryl-ethanol:

[0003] The reaction takes place in a sulfuric acid medium and is catalyzed by a Ru / C catalyst, namely a supported Ru catalyst with carbon powder as the support. Summary of the Invention

[0004] The purpose of this invention is to provide a ruthenium-catalyzed hydrogenation method for acetals that can achieve good yields.

[0005] This objective is achieved by means of the method described in Request 1.

[0006] This method includes the following steps: a) First, add formula ( [Ia]) to formula ( [VIa]) One of the acetals: Where a, c, d, and f are integers from 0 to 12, and b and e are integers from 1 to 12. Furthermore, R1, R2, R3, and R4 are each independently (C1-C12)-alkyl groups; b) Adding a Ru compound capable of forming a complex and a ligand containing a P atom, or Ru-coordination complex, wherein the coordination group of the complex contains a P atom; c) Feed H2; d) Heating the reaction mixture from a) to c) converts the acetal to formula ( [Ib]) to formula ( [VIb]) Compounds: .

[0007] The formula (C1-C12)-alkyl encompasses straight-chain and branched alkyl groups having 1 to 12 carbon atoms. It is preferably (C1-C8)-alkyl, more preferably (C1-C6)-alkyl, and most preferably (C1-C4)-alkyl.

[0008] In a variant of this method, R1 and R2 are the same functional groups.

[0009] In a variant of this method, R3 and R4 are the same group.

[0010] In a variant of this method, R1, R2, R3, and R4 are the same functional groups.

[0011] In a variant of this method, R1, R2, R3, and R4 are (C1-C4)-alkyl groups.

[0012] In a variant of this method, the Ru compound is selected from: RuCl3x 3H2O, [Ru(isopropyltoluene)Cl2]2, RuBr3x 3H2O, RuI3, and Ru(PPh3)3Cl2.

[0013] In a variant of this method, the ligand is a phosphine ligand or a phosphite ligand.

[0014] In a variant of this method, the ligand is a phosphine ligand.

[0015] In a variant of this method, the ligand is selected from: PPh3, 1,4-bis(diphenylphosphine)butane (dppb), 1,1'-ferrocene di-bis(diphenylphosphine) (dppf), bis[2-(diphenylphosphine)phenyl]ether (dpephos), 1,3-bis(diphenylphosphine)propane (dppp), and 4,5-bis(diphenylphosphine)-9,9-dimethyldibenzopiperanone (XantPhos).

[0016] In a variant of this method, H2 is fed at a pressure range of 0.5 MPa (5 bar) to 8 MPa (80 bar).

[0017] In a variant of this method, H2 is fed at a pressure range of 1 MPa (10 bar) to 6 MPa (60 bar).

[0018] In a variant of this method, the reaction mixture is heated to a temperature in the range of 30°C to 100°C.

[0019] In a variant of this method, the reaction mixture is heated to a temperature in the range of 40°C to 80°C.

[0020] In a variant of this method, the method includes an additional method step c'): c') Add solvent.

[0021] In a variant of this method, the solvent is selected from: 1,4-diethane, tetrahydrofuran (THF), and water. Implementation

[0022] The invention will be described in more detail below with reference to operational examples. [Experiment Description] [] General purpose (autoclave)

[0023] Fill an 8 ml vial with appropriate amounts of RuCl3x3H2O, PPh3, and a magnetic stirrer. Seal the vial with a PTFE-coated silicone rubber septum and a phenolic resin cap. Connect the vial to the argon feed line via a needle. Evacuate the vial and refill it with argon three times. Using a syringe, inject the ether solvent (THF or 1,4-dimethyl ether, stored under argon) with appropriate amounts of water and the matrix into the vial, resulting in a dark solution.

[0024] The vial was placed in a stainless steel plate, with the needle remaining in place, to allow for gas exchange within the autoclave. The plate was then placed in a 300 mL autoclave from Parr Instruments' 4760 series under an argon atmosphere. After purging the autoclave three times with hydrogen, the hydrogen pressure was increased to 20 bar / 40 bar at room temperature. The reaction was carried out in the autoclave at 60 °C (temperature of the aluminum block) for 18 hours using a magnetic stirrer on a heating / stirring device. After the reaction time was complete, the autoclave was cooled to room temperature, and the pressure was carefully released. Tetradecanedicarboxylic acid (0.100 mL) was then injected as an internal standard. A) 1,1-Dimethoxynonane to 1-nonanol

[0025] 1.5 ml of THF, 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 RuCl3x3H2O and 5.2 mg (0.8 mol%) of PPh3. H2 was injected to 20 bar, and the reaction was carried out at 60 °C for 18 hours. The yield (GC) was quantitative. Changes in ligands 1,4-Bis(diphenylphosphine)butane (dppb):

[0026] 1.5 ml of dimethyl methoxide, 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 RuCl3x3H2O and 8.5 mg (0.04 mmol, 0.8 mol%) of 1,4-bis(diphenylphosphine)butane. H2 was injected to 20 bar, and the reaction was carried out at 60 °C for 18 hours. The yield (GC) was quantitative. 1,1'-Ferrocene di-di(diphenylphosphine) (dppf):

[0027] 1.5 ml of dimethyl methoxynonane, 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 RuCl3x3H2O and 11.1 mg (0.04 mmol, 0.8 mol%) of 1,1'-ferrocene dimethylbis(diphenylphosphine). H2 was introduced to 20 bar, and the reaction was carried out at 60 °C for 18 hours. The yield (GC) was quantitative. bis[2-(diphenylphosphine)phenyl] ether (dpephos):

[0028] 1.5 ml of dimethyl methoxide, 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 RuCl3x3H2O and 10.8 mg (0.04 mmol, 0.8 mol%) of bis[2-(diphenylphosphine)phenyl] ether. H2 was injected to 20 bar, and the reaction was carried out at 60 °C for 18 hours. The yield (GC) was quantitative. 1,3-Bis(diphenylphosphine)propane (dppp):

[0029] 1.5 ml of dimethyl methoxide, 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 RuCl3x3H2O and 8.2 mg (0.04 mmol, 0.8 mol%) of 1,3-bis(diphenylphosphine)propane. H2 was injected to 20 bar, and the reaction was carried out at 60 °C for 18 hours. The yield (GC) was quantitative. 4,5-Bis(diphenylphosphine)-9,9-dimethyldibenzopiperanone (XantPhos):

[0030] 1.5 ml of dimethyl methoxynonane, 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 RuCl3x3H2O and 11.6 mg (0.02 mmol, 0.8 mol%) of 4,5-bis(diphenylphosphine)-9,9-dimethyldibenzopiperan. H2 was added to 20 bar, and the reaction was carried out at 60 °C for 18 hours. The yield (GC) was 59%. Changes in Ru compounds [Ru(isopropyltoluene)Cl2]2:

[0031] Dimethyl methoxynonane (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 were added to 3.1 mg (0.4 mol% ruthenium) of [Ru(isopropyltoluene)Cl2]2 and 10.5 mg (0.04 mmol, 1.6 mol%) of PPh3. H2 was injected to 20 bar, and the reaction was carried out at 60 °C for 18 hours. The yield (GC) was quantitative. RuBr3x 3H2O:

[0032] Dimethyl methoxynonane (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 were added to 3.9 mg (0.4 mol% ruthenium) of RuBr3x3H2O and 10.5 mg (0.04 mmol, 1.6 mol%) of PPh3. H2 was injected to 20 bar, and the reaction was carried out at 60 °C for 18 hours. The yield (GC) was 93%. RuI3:

[0033] Dimethyl methoxynonane (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 were added to 4.8 mg (0.4 mol% ruthenium) of RuI3 and 10.5 mg (0.04 mmol, 1.6 mol%) of PPh3.

[0034] H2 was injected to 20 bar, and the reaction was carried out at 60°C for 18 hours. The yield (GC) was 75%. Ru(PPh3)3Cl2:

[0035] 1.5 ml of dimethoxynonane, 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 (0.4 mol% ruthenium) of Ru(PPh3)3Cl2 and 2.6 mg (0.01 mmol, 0.4 mol%) of PPh3. H2 was injected to 20 bar, and the reaction was carried out at 60 °C for 18 hours. The yield (GC) was quantitative. Changes in acetal B) 1,1,6,6-Tetramethoxyhexane to hexane-1,6-diol

[0036] 1,4-Dimethyl methoxide (6 ml, absolute), 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 RuCl3x3H2O, and 42 mg (1.6 mol%) of PPh3 were added to a vial. H2 was injected to 40 bar, and the reaction was carried out at 60 °C for 18 hours. The GC yield was 81%. C) 1,1,6,6-Tetrabutoxyhexane to hexane-1,6-diol

[0037] 1.5 ml of THF, 0.99 g (2.64 mmol) of 1,1,6,6-tetrabutoxyhexane, 0.72 ml of H₂O, 2.6 mg (0.38 mol%) of RuCl₃x₃H₂O, and 10.5 mg (1.52 mol%) of PPh₃ were added to a vial. H₂ was injected to 20 bar, and the reaction was carried out at 60 °C for 18 hours. The GC yield was 90%. D) 1,1,4,4-Tetramethoxybutane to butane-1,4-diol

[0038] 1.5 ml of dimethyl ether, 0.54 ml of water, 0.46 g (2.56 mmol) of 1,1,4,4-tetramethoxybutane, 2.6 mg (0.39 mol%) of RuCl3x3H2O, and 10.5 mg (1.56 mol%) of PPh3 were added to a vial. H2 was injected to 20 bar, and the reaction was carried out at 60 °C for 18 hours. The NMR yield was 66%. E) Benzaldehyde dimethyl acetal to benzyl alcohol

[0039] 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 RuCl₃x₃H₂O, and 5.2 mg (0.73 mol%) of PPh₃ were added to a vial. H₂ was injected to 20 bar, and the reaction was carried out at 60 °C for 18 hours. The GC yield was >99%. F) Phenylacetaldehyde dimethyl acetal to 2-phenylethanol

[0040] 1.5 ml of dimethyl ether, 0.36 g of H₂O, 0.42 g (2.5 mmol) of phenylacetaldehyde dimethyl acetal, 2.6 mg (0.4 mol%) of RuCl₃x₃H₂O, and 10.5 mg (1.6 mol%) of PPh₃ were added to a vial. H₂ was injected to 20 bar, and the reaction was carried out at 60 °C for 18 hours. The GC yield was >99%. G) 4-Methyl-2-octyl-1,3-dioxolane to 1-nonanol

[0041] 1,4-Dimethyl alkylene (1.5 ml, absolute), 0.135 ml (7.5 mmol) of water, 0.5 ml of 4-methyl-2-octyl-1,3-dioxolane (0.47 g, 2.3 mmol), 2.6 mg (0.4 mol%) of RuCl3x3H2O, and 10.5 mg (1.6 mol%) of PPh3 were added to a vial. H2 was injected to 40 bar, and the reaction was carried out at 60 °C for 18 hours. The GC yield was 89%. H) 2,5-Dimethoxytetrahydrofuran (cis / trans mixture) to butane-1,4-diol

[0042] 1.5 ml of dimethyl ether, 0.18 ml of water, 0.33 g (2.5 mmol) of 2,5-dimethoxytetrahydrofuran (cis / trans mixture), 2.6 mg of RuCl3x3H2O, and 10.5 mg (1.6 mol%) of PPh3 were added to a vial. H2 was injected to 20 bar, and the reaction was carried out at 60 °C for 18 hours. The GC yield was 84%. I) 3-Ethoxypropanal diacetal to 3-ethoxypropanol

[0043] 1.5 ml of diacetyl, 0.27 g of H₂O, 0.451 g (2.56 mmol) of ethoxypropionaldehyde diacetal, 2.6 mg (0.39 mol%) of RuCl₃x₃H₂O, and 10.5 mg (1.56 mol%) of PPh₃ were added to a vial. H₂ was injected to 20 bar, and the reaction was carried out at 60 °C for 18 hours. The GC yield was >99%. Changes in the catalyst system J) Phenylacetaldehyde dimethyl acetal to 2-phenylethanol

[0044] Weigh the solid catalyst into an 8 ml vial and add all the liquid using a syringe. Add the matrix last.

[0045] Test the following catalyst systems: catalyst [1]: 0.4 mol% RuCl3x 3 H2O, 1.6 mol% PPh3, 0.36 ml water, 1.5 ml dimethyl ether catalyst [2]:Ru / C 5%(Strem)44-4065 LOT#:21539500, 50% water content, calculated as 0.67 mol% metal, 0.17 ml of 0.1 M H2SO4 (aq), 1.34 ml of water, and 1.5 ml of methanol. catalyst [3]: Ru / C 5% (Johnson-Matthey) Type 622, LOT KS0004, 0.17 ml of 0.1 M H2SO4 (aq), 1.34 ml of water, and 1.5 ml of methanol.

[0046] After the reaction, diglyme was added as a GC standard.

[0047] Reaction conditions: 2.5 mmol matrix, 20 bar H2, 60°C, 5 hours.

[0048] The experimental results are listed in the table below: catalyst Yield Catalyst 1* > 98% Catalyst 2 52% Catalyst 3 56% *Catalyst system according to the present invention

[0049] Experimental results show that the method according to the present invention can achieve this objective.

Claims

1. A method for the ruthenium-catalyzed hydrogenation of an acetal, comprising the following steps: a) Firstly, adding an acetal of one of formulas (Ia) to (VIa): wherein a, c, d, and f are integers from 0 to 12, and b and e are integers from 1 to 12, and R1, R2, R3, and R4 are each independently C1-C12 alkyl groups; b) Adding a Ru compound capable of forming a complex and a coordinating group containing a P atom, or a Ru-coordinating group complex, wherein the coordinating group of the complex contains a P atom, wherein the Ru compound is selected from: RuCl3 x 3H2O, [Ru(isopropyltoluene)Cl2]2, RuBr3 x 3H2O, RuI3, Ru(PPh3)3Cl2; c') Adding a solvent, wherein the solvent is selected from: 1,4-diethane, tetrahydrofuran (THF), and water; c) Feeding H2; d) The reaction mixture from a) to c) is heated, and the acetal is converted into compounds of formula (Ib) to (VIb): .

2. The method of claim 1, wherein R1 and R2 are the same functional groups.

3. The method of claim 1, wherein R3 and R4 are the same functional groups.

4. The method of claim 1, wherein R1, R2, R3, and R4 are C1-C4 alkyl groups.

5. The method of claim 1, wherein the Ru compound is RuCl3 x 3H2O.

6. The method of claim 1, wherein the ligand is a phosphine ligand.

7. The method of claim 1, wherein the ligand is selected from: PPh3, 1,4-bis(diphenylphosphine)butane (dppb), 1,1'-ferrocene dimethylbis(diphenylphosphine) (dppf), bis[2-(diphenylphosphine)phenyl]ether (dpephos), 1,3-bis(diphenylphosphine)propane (dppp), and 4,5-bis(diphenylphosphine)-9,9-dimethyldibenzopiperanone (XantPhos).

8. The method of claim 1, wherein H2 is fed at a pressure range of 0.5 MPa (5 bar) to 8 MPa (80 bar).

9. The method of claim 1, wherein the reaction mixture is heated to a temperature in the range of 30°C to 100°C.

10. The method of claim 1, wherein the solvent is 1,4-dimethylamine and water.