PROCESS FOR THE RUTHENIUM-CATALYSED HYDROGENATION OF ALDEHYDE ACETALS

Abstract

Process for the ruthenium-catalysed hydrogenation of aldehyde acetals.

Claims

1. Process comprising the process steps of: a) initially charging an aldehyde acetal of one of formulae (Ia) to (VIa): ##STR00014## where a, c, d, f are an integer from 0 to 12 and b, e are an integer from 1 to 12 and R.sup.1, R.sup.2, R.sup.3, R.sup.4, each independently, are (C.sub.1-C.sub.12)-alkyl; b) adding an Ru compound capable of forming a complex and a ligand comprising a P atom, or an Ru-ligand complex, where the ligand of the complex comprises a P atom; c) feeding in H.sub.2; d) heating the reaction mixture from a) to c), with conversion of the aldehyde acetal to a compound of formula (Tb) to (VIb): ##STR00015##

2. Process according to claim 1, wherein R.sup.1, R.sup.2 are the same radical.

3. Process according to claim 1, wherein R.sup.3, R.sup.4 are the same radical.

4. Process according to claim 1, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 are (C.sub.1-C.sub.4)-alkyl.

5. Process according to claim 1, wherein the Ru compound is selected from: RuCl.sub.33H.sub.2O, [Ru(cymene)Cl.sub.2].sub.2, RuBr.sub.33H.sub.2O, RuI.sub.3, Ru(PPh.sub.3).sub.3Cl.sub.2.

6. Process according to claim 1, wherein the ligand is a phosphine ligand.

7. Process according to claim 1, wherein the ligand is selected from: PPh.sub.3, 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).

8. Process according to claim 1, wherein H.sub.2 is fed in with a pressure in the range from 0.5 MPa (5 bar) to 8 MPa (80 bar).

9. Process according to claim 1, wherein the reaction mixture is heated to a temperature in the range from 30 C. to 100 C.

10. Process according to claim 1, comprising the additional process step c): c) adding a solvent.

11. Process according to claim 10, wherein the solvent is selected from: 1,4-dioxane, tetrahydrofuran (THF), water.

Description

EXPERIMENTAL DESCRIPTION

General (Autoclave)

[0030] An 8 ml vial was filled with the appropriate amounts of RuCl.sub.33H.sub.2O, PPh.sub.3 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.

A) 1,1-Dimethoxynonane to 1-nonanol

##STR00004##

[0031] 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 RuCl.sub.33H.sub.2O and 5.2 mg (0.8 mol %) of PPh.sub.3. H.sub.2 is injected to 20 bar and the reaction is carried out at 60 C. for 18 h. Yield (GC) quantitative.

Variation of the Ligand

1,4-Bis(diphenylphosphino)butane (dppb)

[0032] 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 RuCl.sub.33H.sub.2O and 8.5 mg (0.04 mmol, 0.8 mol %) of 1,4-bis(diphenylphosphino)butane. H.sub.2 is injected to 20 bar and the reaction is carried out at 60 C. for 18 h. Yield (GC) quantitative.

1,1-Ferrocenediylbis(diphenylphosphine) (dppf)

[0033] 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 RuCl.sub.33H.sub.2O and 11.1 mg (0.04 mmol, 0.8 mol %) of 1,1-ferrocenediylbis(diphenylphosphine). H.sub.2 is injected to 20 bar and the reaction is carried out at 60 C. for 18 h. Yield (GC) quantitative.

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

[0034] 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 RuCl.sub.33H.sub.2O and 10.8 mg (0.04 mmol, 0.8 mol %) of bis[2-(diphenylphosphino)phenyl]ether. H.sub.2 is injected to 20 bar and the reaction is carried out at 60 C. for 18 h. Yield (GC) quantitative.

1,3-Bis(diphenylphosphino)propane (dppp)

[0035] 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 RuCl.sub.33H.sub.2O and 8.2 mg (0.04 mmol, 0.8 mol %) of 1,3-bis(diphenylphosphino)propane. H.sub.2 is injected to 20 bar and the reaction is carried out at 60 C. for 18 h. Yield (GC) quantitative.

4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (XantPhos)

[0036] 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 RuCl.sub.33H.sub.2O and 11.6 mg (0.02 mmol, 0.8 mol %) of 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene. H.sub.2 is injected to 20 bar and the reaction is carried out at 60 C. for 18 h. Yield (GC) 59%.

Variation of the Ru Compound

[Ru(cymene)Cl.SUB.2.].SUB.2

[0037] 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)Cl.sub.2].sub.2 and 10.5 mg (0.04 mmol, 1.6 mol %) of PPh.sub.3. H.sub.2 is injected to 20 bar and the reaction is carried out at 60 C. for 18 h. Yield (GC) quantitative.

RuBr.SUB.3.3H.SUB.2.O

[0038] 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 RuBr.sub.33H.sub.2O and 10.5 mg (0.04 mmol, 1.6 mol %) of PPh.sub.3. H.sub.2 is injected to 20 bar and the reaction is carried out at 60 C. for 18 h. Yield (GC) 93%.

RuI.SUB.3

[0039] 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 RuI.sub.3 and 10.5 mg (0.04 mmol, 1.6 mol %) of PPh.sub.3.

[0040] H.sub.2 is injected to 20 bar and the reaction is carried out at 60 C. for 18 h. Yield (GC) 75%.

Ru(PPh.SUB.3.).SUB.3.Cl.SUB.2

[0041] 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(PPh.sub.3).sub.3Cl.sub.2 and 2.6 mg (0.01 mmol, 0.4 mol %) of PPh.sub.3. H.sub.2 is injected to 20 bar and the reaction is carried out at 60 C. for 18 h. Yield (GC) quantitative.

Variation of the Aldehyde Acetal

B) 1,1,6,6-Tetramethoxyhexane to hexane-1,6-diol

##STR00005##

[0042] 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 RuCl.sub.33H.sub.2O and 42 mg (1.6 mol %) of PPh.sub.3 are added to a vial. H.sub.2 is injected to 40 bar and the reaction is carried out at 60 C. for 18 h. The GC yield is 81%.

C) 1,1,6,6-Tetrabutoxyhexane to hexane-1,6-diol

##STR00006##

[0043] 1.5 ml of THF, 0.99 g (2.64 mmol) of 1,1,6,6-tetrabutoxyhexane and 0.72 ml of H.sub.2O, 2.6 mg (0.38 mol %) of RuCl.sub.33H.sub.2O and 10.5 mg (1.52 mol %) of PPh.sub.3 are added to a vial. H.sub.2 is injected to 20 bar and the reaction is carried out at 60 C. for 18 h. The GC yield is 90%.

D) 1,1,4,4-Tetramethoxybutane to butane-1,4-diol

##STR00007##

[0044] 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 RuCl.sub.33H.sub.2O and 10.5 mg (1.56 mol %) of PPh.sub.3 are added to a vial. H.sub.2 is injected to 20 bar and the reaction is carried out at 60 C. for 18 h. The NMR yield is 66%.

E) Benzaldehyde Dimethyl Acetal to Benzyl Alcohol

##STR00008##

[0045] 1.5 ml of THF, 0.135 g of H.sub.2O and 0.42 g (2.72 mmol) of benzaldehyde dimethyl acetal, 1.3 mg (0.18 mol %) of RuCl.sub.33H.sub.2O and 5.2 mg (0.73 mol %) of PPh.sub.3 are added to a vial. H.sub.2 is injected to 20 bar and the reaction is carried out at 60 C. for 18 h. The GC yield is >99%.

F) Phenylacetaldehyde Dimethyl Acetal to 2-Phenylethanol

##STR00009##

[0046] 1.5 ml of dioxane, 0.36 g of H.sub.2O and 0.42 g (2.5 mmol) of phenylacetaldehyde dimethyl acetal, 2.6 mg (0.4 mol %) of RuCl.sub.33H.sub.2O and 10.5 mg (1.6 mol %) of PPh.sub.3 are added to a vial. H.sub.2 is injected to 20 bar and the reaction is carried out at 60 C. for 18 h. The GC yield is >99%.

G) 4-Methyl-2-octyl-1,3-dioxolane to 1-nonanol

##STR00010##

[0047] 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 RuCl.sub.33H.sub.2O and 10.5 mg (1.6 mol %) of PPh.sub.3 are added to a vial. H.sub.2 is injected to 40 bar and the reaction is carried out at 60 C. for 18 h. The GC yield is 89%.

H) 2,5-Dimethoxytetrahydrofuran (Cis/Trans Mixture) to Butane-1,4-Diol

##STR00011##

[0048] 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 RuCl.sub.33H.sub.2O and 10.5 mg (1.6 mol %) of PPh.sub.3 are added to a vial. H.sub.2 is injected to 20 bar and the reaction is carried out at 60 C. for 18 h. The GC yield is 84%.

I) 3-Ethoxypropionaldehyde diethyl acetal to 3-ethoxypropanol

##STR00012##

[0049] 1.5 ml of dioxane, 0.27 g of H.sub.2O and 0.451 g (2.56 mmol) of ethoxypropionaldehyde diethyl acetal, 2.6 mg (0.39 mol %) of RuCl.sub.33H.sub.2O and 10.5 mg (1.56 mol %) of PPh.sub.3 are added to a vial. H.sub.2 is injected to 20 bar and the reaction is carried out at 60 C. for 18 h. The GC yield is >99%.

Variation of the Catalyst System

J) Phenylacetaldehyde dimethyl acetal to 2-phenylethanol

##STR00013##

[0050] The solid catalyst was weighed out in 8 ml vials and all liquids were added with the syringe. The substrate was added last here.

[0051] The following catalyst systems were tested: [0052] Cat 1: 0.4 mol % of RuCl.sub.33 H.sub.2O, 1.6 mol % of PPh.sub.3, 0.36 ml of water, 1.5 ml of dioxane [0053] Cat 2: Ru/C 5% (Strem) 44-4065 LOT #:21539500, 50% water content, calculated for 0.67 mol % of metal, 0.17 ml of 0.1 M H.sub.2SO.sub.4 (aq), 1.34 ml of water, 1.5 ml of methanol [0054] Cat 3: Ru/C 5% (Johnson-Matthey) Type 622, LOT KS0004, 0.17 ml of 0.1 M H.sub.2SO.sub.4 (aq), 1.34 ml of water, 1.5 ml of methanol

[0055] Diglyme was added, after the reaction, as GC standard.

Reaction Conditions:

[0056] 2.5 mmol of substrate, 20 bar of H.sub.2, 60 C., 5 h.

[0057] The experimental results are listed in the following table:

TABLE-US-00001 Catalyst Yield Cat 1* >98% Cat 2 52% Cat 3 56% *catalyst system according to the invention

[0058] As the experimental results show, the object is achieved by the process according to the invention.