PROCESS FOR THE PREPARATION OF [RU(OAC)2(LIGAND)] CATALYSTS

Abstract

The invention comprises a process for the preparation of a [Ru(OAc).sub.2(Ligand)] catalysts of the formula I

##STR00001##

wherein R.sup.1 is C.sub.1-6 alkyl and R.sup.3 is hydrogen or C.sub.1-6 alkyl and R.sup.4 is hydrogen or C.sub.1-6-alkoxy.

[Ru(OAc).sub.2(Ligand)] catalysts are versatile hydrogenation catalysts.

Claims

1. A process for the preparation of a [Ru(OAc).sub.2(Ligand)] catalysts of the formula I and its enantiomers, ##STR00006## wherein R.sup.1 is C.sub.1-6 alkyl and R.sup.3is hydrogen or C.sub.1-6 alkyl and R.sup.4 is hydrogen or C.sub.1-6-alkoxy, comprising the conversion of a phosphine precursor of the formula II ##STR00007## wherein R.sup.1, R.sup.3 and R.sup.4 are as above, with [Ru(OAc).sub.2(p-cymene)], wherein Ac stands for acetyl, to the [Ru(OAc).sub.2(Ligand)] catalyst of the formula I in the presence of a non-polar solvent at a reaction temperature of 40 C. to 110 C.

2. The process of claim 1, wherein R.sup.1 is methyl.

3. The process of claim 1, wherein R.sup.3 is C.sub.1-4-alkyl, preferably t-butyl.

4. The process of claim 1, wherein R.sup.4 is hydrogen or C.sub.1-4-alkoxy, preferably hydrogen or methoxy.

5. The process of claim 1, wherein the non-polar solvent is selected from tetrahydrofuran, toluene, benzene, 1,4-dioxane and 2-methyltetrahydrofuran, preferably from 2-methyltetrahydrofuran.

6. The process of claim 1, wherein the reaction temperature is between 40 C. and 110 C.

7. The process of claim 1, wherein the conversion is conducted under inert gas atmosphere.

8. The process of claim 1, wherein the [Ru(OAc).sub.2(Ligand)] catalysts of the formula I are isolated by a solvent exchange wherein the non-polar solvent is replaced by and anti-solvent.

9. The process of claim 8, wherein the anti-solvent is selected from the group consisting of liner C.sub.5-10 alkanes and branched C.sub.5-10 alkanes.

10. The process of claim 8, wherein the wherein the anti-solvent is selected from the group consisting of n-pentane, n-hexane, and n-heptane.

Description

EXAMPLES

[0035] Abbreviations:

TABLE-US-00001 MeTHF 2-Methyl-tetrahydrofuran DCM Dichloromethane n-Hexane Hexane rt room temperature [RuCl.sub.2(p-cymene)].sub.2 Dichloro(p-cymene)ruthenium(II) dimer, CAS # 52462-29-0, commercially available from Strem Chemicals Ltd. [Ru(OAc).sub.2(p-cymene)] Diacetato(p-cymene)ruthenium(II), was synthesized in analogy to M.A. Bennett et al. J. Chem. Soc. Dalton Trans. 1983, 1571- 1581, b P. H. Dixneuf et al., Green Chem. 2011, 13, 3075-3078 (R)MeOBIPHEP (R)-(+)-(6,6-Dimethoxybiphenyl-2,2- diyl)bis(diphenylphosphine), CAS # 133545-16-1 commercially available from Solvias AG (R)-3,5-tBu-4-MeOMeOBIPHEP (R)-(6,6-Dimethoxybiphenyl-2,2- diyl)bis[bis(3,5-di-tert-butyl-4- methoxyphenyl)phosphine], CAS # 352655-61-9, commercially available from Solvias AG (R)-3,5-tBuMeOBIPHEP (R)-(6,6-Dimethoxybiphenyl-2,2- diyl)bis[bis(3,5-di-tert-butyl- phenyl)phosphine], CAS # 192138-05-9, commercially available from Solvias AG [Ru(OAc).sub.2((R)MeOBIPHEP)] Diacetato[(R)-(6,6-dimethoxybiphenyl- 2,2-diyl)bis(diphenylphosphine)] ruthenium(II [Ru(OAc).sub.2((R)-3,5-tBu-4-MeOMeOBIPHEP)] Diacetato[(R)-(6,6-dimethoxybiphenyl- 2,2-diyl)bis[bis(3,5-di-tert-butyl-4- methoxyphenyl)phosphine]]ruthenium(II) [Ru(OAc).sub.2((R)-3,5-tBuMeOBIPHEP)] Diacetato[(R)-(6,6-dimethoxybiphenyl- 2,2-diyl)bis[bis(3,5-di-tert-butyl- phenyl)phosphine]]ruthenium(II)

Example 1

Synthesis of [Ru(OAc).SUB.2.(p-cymene)]

Example 1.1

[0036] Under argon atmosphere, a 2-L round bottomed flask topped with an argon inlet and a Teflon-coated stirring bar was charged with [RuCl.sub.2(p-cymene)].sub.2 (82.5 g, 0.14 mol) and silver acetate (98.9 g, 0.59 mol). Toluene (750 mL) was added and the resulting yellow-brown suspension was stirred at rt for 23 h (complete conversion determined by .sup.1H-NMR spectroscopy). DCM (100 mL) was added and the suspension was filtered over a high porosity glass sintered filter (P3) covered with a 2-cm pad of pressed filter flocs (MN2101, Macherey-Nagel). The filter cake was rinsed with DCM (300 mL) and the combined filtrates were evaporated to dryness at 50 mbar/45 C. The dark red residue was dissolved in DCM (150 mL) and filtered over a high porosity glass sintered filter (P3) covered with a 2-cm pad of pressed filter flocs. The filter cake was rinsed with DCM (75 mL). To the combined filtrates, hexane (100 mL) was added and the solution concentrated at 400 mbar/35 C. to approx. half-volume. Hexane (100 mL) was added and the solution concentrated at 400 mbar/35 C. to approx. half-volume. This operation was repeated once to remove residual DCM, respectively to precipitate the product. The formed suspension was stirred at rt for 30 min and the light yellow supernatant was removed by suction with a tube equipped with a filter candle. The crystalline residue was washed with hexane (600 mL) in 3 portions whereby the supernatant was each time removed by suction with a tube equipped with a filter candle. The residue was dried overnight at 1 mbar/rt to yield the title compound (86.7 g, 91%) as a yellow-brown powder.

Example 1.2

[0037] Under argon atmosphere, a 100-mL round bottomed flask topped with an argon inlet and a Teflon-coated stirring bar was charged with [RuCl.sub.2(p-cymene)].sub.2 (5.0 g, 8.2 mmol) and potassium acetate (4.0 g, 40.8 mmol). Toluene (50 mL) was added and the resulting red suspension was stirred at rt for 24 h (complete conversion determined by .sup.1H-NMR spectroscopy). DCM (20 mL) was added and the suspension was filtered over a high porosity glass sintered filter (P3) covered with a 2-cm pad of pressed filter flocs (MN2101, Macherey-Nagel). The filter cake was rinsed with DCM (80 mL) and the combined filtrates were evaporated to dryness at 50 mbar/50 C. MeTHF (25 mL) were added to the dark red residue and the mixture was heated to 75 C. for 15 min to yield a dark red solution. After cooling to rt, the formed suspension was stirred in an ice bath for 30 min and the crude product was filtered off on a high porosity glass sintered filter (P3). The filter cake was washed with cold MeTHF (5 mL) and dried overnight at 1 mbar/rt to yield the title compound (5.0 g, 86%) as a yellow-brown powder.

[0038] .sup.1H-NMR (400 MHZ, CDCl.sub.3): (ppm) 5.80 (d, J=5.9 Hz, 2H), 5.58 (d, J=6.2 Hz, 2H), 2.86 (spt, J=6.9 Hz, 1H), 2.26 (s, 3H), 1.93 (s, 6H), 1.36 (d, J=6.7 Hz, 6H)

Example 2

Synthesis of [Ru(OAc).SUB.2.((R)-3,5-tBu-4-MeO-MeOBIPHEP)]

[0039] Under argon atmosphere, a 250-mL Schlenk flask equipped with a reflux condenser topped with an argon inlet and a Teflon-coated magnetic stirring bar was charged with of (R)-3,5-tBu-4-MeO-MeOBIPHEP (10.0 g, 8.68 mmol) and [Ru(OAc).sub.2(p-cymene)] (3.1 g, 8.68 mmol. MeTHF (80 mL) was added and the resulting brown suspension was stirred at 85 C. (jacket temperature) for 40 h to reach a conversion of 91% (determined by .sup.31P-NMR spectroscopy). The reaction mixture was allowed to cool to rt and concentrated at 100-300 mbar to a volume of 30-40 mL. Hexane (40 mL) was added, the resulting brown solution was cooled in an ice bath and filtered over a high porosity glass sintered filter (P3) covered with a 2-cm pad of pressed filter flocs (MN2101, Macherey-Nagel). The filter cake was rinsed with hexane (25 mL) and the combined filtrates were concentrated at 100-300 mbar/rt to a volume of 30-40 mL. Another portion of hexane (40 mL) was added and the resulting solution was concentrated at 100-300 mbar/rt to a volume of 30-40 mL to remove residual MeTHF. Subsequently, hexane (40 mL) was added and the formed suspension was stirred overnight at rt, then cooled in an ice bath, stirred for 1 h and filtered off on a high porosity glass sintered filter (P3). The filter cake was rinsed with hexane (20 mL) and dried for 4 h at 0.05-0.1 mbar/rt to yield the title compound (9.2 g, 77%) as an orange solid with >99% purity (determined by .sup.31P-NMR).

[0040] .sup.31P-NMR (162 MHz, CDCl.sub.3): (ppm) 66.6 (s). Residual solvents: MeTHF (0.03 wt % (GC)), hexane (0.11 wt % (GC)), H.sub.2O (<0.1 wt % (Karl Fischer)).

Example 3

Synthesis of [Ru(OAc).SUB.2.((R)-3,5-tBu-MeOBIPHEP)]

[0041] Under argon atmosphere, a 250-mL Schlenk flask equipped with a reflux condenser topped with an argon inlet and a Teflon-coated magnetic stirring bar was charged with of (R)-3,5-tBu-MeOBIPHEP (10.0 g, 9.70 mmol) and [Ru(OAc).sub.2(p-cymene)] (3.8 g, 10.78 mmol). MeTHF (80 mL) was added and the resulting brown suspension was stirred at 85 C. (jacket temperature) for 24 h to reach a conversion of 94% (determined by .sup.31P-NMR spectroscopy). The reaction mixture was allowed to cool to rt and concentrated at 100-300 mbar to a volume of 30-40 mL. Hexane (40 mL) was added and the resulting solution was concentrated at 100-300 mbar to a volume of 30-40 mL. This operation was repeated once to remove residual MeTHF. Subsequently, hexane (40 mL) was added and the solution was stirred overnight at rt. The reaction mixture was then heated to 40 C. and filtered on a high porosity glass sintered filter (P3) with a 2-cm pad of pressed filter flocs (MN2101, Macherey-Nagel). The filter cake was rinsed with hexane (30 mL) and the combined filtrates were concentrated at 100-300 mbar/rt to a volume of 30 mL. The resulting dark brown suspension was heated to 60 C. to deliver a clear solution which was then cooled to 0-5 C. The formed precipitate was filtered off on a high porosity glass sintered filter (P3), the filter cake was washed with hexane (30 mL) and dried overnight at 0.05-0.1 mbar/rt to yield the title compound (9.4 g, 70%) as a yellow solid with 98% purity (determined by .sup.31P-NMR) containing 2% (R)-3,5-tBu-MeOBIPHEP.

[0042] Optionally, the yellow solid can be recrystallized from hexane at 60 C. (as described above) to yield .sup.31P-NMR pure (>99.5%) [Ru(OAc).sub.2((R)-3,5-tBu-MeOBIPHEP)] (8.8 g, 65% overall yield).

[0043] .sup.31P-NMR (162 MHz, CDCl.sub.3): (ppm) 67.5 (s). Residual solvents: MeTHF (0.00 wt % (GC)), hexane (1.15 wt % (GC)), H.sub.2O (<0.1 wt % (Karl Fischer))

Example 4

Synthesis of [Ru(OAc).SUB.2.((R)-MeOBIPHEP)]

[0044] Under argon atmosphere, a 100-mL Schlenk flask equipped with a reflux condenser topped with an argon inlet and a Teflon-coated magnetic stirring bar was charged with of (R)-MeOBIPHEP (5.0 g, 8.58 mmol) and [Ru(OAc).sub.2(p-cymene)] (3.0 g, 8.58 mmol). MeTHF (40 mL) was added and the resulting brown suspension was stirred at 85 C. (jacket temperature) for 20 h to reach a conversion of >99.5% (determined by .sup.31P-NMR spectroscopy). The reaction mixture was allowed to cool to rt and concentrated at 100-300 mbar to a volume of 35 mL. The solution was filtered on a high porosity glass sintered filter (P3) with a 1.5-cm pad of pressed filter flocs (MN2101, Macherey-Nagel). The filter cake was rinsed with MeTHF (15 mL). Hexane (40 mL) was added to the combined filtrates and the resulting dark suspension was cooled in an ice bath and stirred for 1 h. The solid was filtered off on a high porosity glass sintered filter (P3), the filter cake was washed with ice-cold MeTHF (40 mL) and dried for 72 h at 0.05-0.1 mbar/rt to yield the title compound (4.2 g, 61%) as a yellow solid with >99.5% purity (determined by .sup.31P-NMR)

[0045] .sup.31P-NMR (162 MHz, CDCl.sub.3): (ppm) 63.4 (s). Residual solvents: MeTHF (0.03 wt % (GC)), hexane (0.11 wt % (GC)), H.sub.2O (0.3 wt % (Karl Fischer)).

Examples 5.1-5.3

Synthesis of [Ru(OAc).SUB.2.((R)-3,5-tBu-4-MeO-MeOBIPHEP)]

[0046] In analogy to Example 2, (R)-3,5-tBu-4-MeO-MeOBIPHEP (500 mg, 0.434 mmol) and [Ru(OAc).sub.2(p-cymene)] (153 mg, 0.434 mmol) were dissolved in 4 ml DCM or MeTHF and the resulting suspensions stirred at the temperatures as stated in Table 1. To determine the conversion at different time points, the reaction mixtures were sampled and analyzed by .sup.31P-NMR spectroscopy.

TABLE-US-00002 TABLE 1 Conversion Conversion Conversion Conversion Example Solvent Temp..sup.1 after 3 h after 6 h after 24 h after 48 h 5.1 DCM 40 C. 1 4 13 31 5.2 MeTHF 40 C. 8 17 45 64 5.3 MeTHF 85 C. 51 69 90 94 .sup.1jacket temperature

Examples 6.1-6.3

Synthesis of [Ru(OAc).SUB.2.((R)-MeOBIPHEP)]

[0047] In analogy to Example 4, (R)-MeOBIPHEP (250 mg, 0.429 mmol) and [Ru(OAc).sub.2(p-cymene)] (151 mg, 0.429 mmol) were dissolved in 4 ml DCM or MeTHF and the resulting suspensions stirred at the temperatures as stated in Table 2. To determine the conversion at different time points, the reaction mixtures were sampled and analyzed by .sup.31P-NMR spectroscopy.

TABLE-US-00003 TABLE 2 Conversion Conversion Conversion Example Solvent Temp..sup.1 after 3 h after 6 h after 24 h 6.1 DCM 40 C. 51 71 96 6.2 MeTHF 40 C. 76 86 96 6.3 MeTHF 85 C. 98 99 .sup.1jacket temperature