Hydrogenation of imines with Ru complexes

Abstract

Described herein are catalytic hydrogenation and the use of ruthenium complexes having a bidentate diphosphine ligand or two monodentate phosphine ligands, two carboxylate ligands, and optionally a diamine ligand in hydrogenation processes for the reduction of imines into the corresponding amines.

Claims

1. A process for the reduction by hydrogenation, using molecular H.sub.2, of a C.sub.5-C.sub.20 substrate of formula ##STR00051## wherein R.sup.a and R.sup.c represent, independently from each other, a hydrogen atom or a C.sub.1-C.sub.15 hydrocarbon group optionally comprising one to three oxygen atoms and/or one to two nitrogen atoms and/or one sulphur or halogen atom; R.sup.b represents a C.sub.1-C.sub.15 hydrocarbon group optionally comprising one to three oxygen atoms and/or one to two nitrogen atoms and/or one sulphur or halogen atom, a hydrogen atom, a SO.sub.2R.sup.b′, a OR.sup.b″ or a POR.sup.b′.sub.2 group wherein R.sup.b′ represents a C.sub.1-C.sub.6 alkyl group or a phenyl or tolyl group and R.sup.b′ represents a hydrogen atom, a C.sub.1-C.sub.6 alkyl group or a phenyl or tolyl group; or R.sup.a and R.sup.c represent, when taken together, a C.sub.1-C.sub.10 alkanediyl or alkenediyl group; provided that at least one R.sup.a, R.sup.b, or R.sup.c is not a hydrogen atom; into the corresponding amine, wherein said process is carried out in the presence of at least one catalyst or pre-catalyst of formula
[Ru(PP)(NN).sub.n(RCOO).sub.2](1) or [Ru(P).sub.2(NN).sub.n(RCOO).sub.2]  (1′) wherein n is 0 or 1; PP represents a C.sub.5-C.sub.50 bidentate ligand wherein the coordinating groups are two phosphino groups; P represents a C.sub.3-C.sub.50 monodentate ligand; NN represents a C.sub.2-C.sub.20 bidentate ligand wherein the coordinating atoms are two nitrogen atoms; and each R represents, simultaneously or independently, a hydrogen atom, a C.sub.1-C.sub.12 linear hydrocarbon group, or a branched or cyclic C.sub.3-C.sub.12 hydrocarbon group and said hydrocarbon group comprises optionally one to five heteroatoms selected amongst halogen, oxygen and nitrogen atoms; and wherein the process is performed in the absence of a base additive.

2. The process according to claim 1, wherein R.sup.a, R.sup.b and R.sup.c represent, independently from each other, a hydrogen atom, a C.sub.1-C.sub.10 linear alkyl group, a C.sub.2-C.sub.10 linear alkenyl group, a C.sub.3-C.sub.10 linear, branched, or cyclic alkyl or alkenyl group, a C.sub.4-C.sub.10 linear, branched, or cyclic alkadienyl group, a C.sub.3-8 aryl, a C.sub.2-8 heterocyclic, or a C.sub.6-12 arylalkyl group optionally substituted by a hydroxyl group, a C.sub.1-6 alkyl group or a C.sub.1-6 alkoxy group; or R.sup.a and R.sup.c represent, when taken together, a C.sub.1-C.sub.10 alkanediyl or alkenediyl group; provided that at least one R.sup.a, R.sup.b, or R.sup.c is not a hydrogen atom.

3. The process according to claim 1, wherein R.sup.c is a hydrogen atom.

4. The process according to claim 1, wherein R.sup.a or R.sup.b represent a C.sub.2-6 heterocyclic group optionally substituted by a hydroxyl group, a C.sub.1-3 alkyl group, or a C.sub.1-3 alkoxy group and the other represents a C.sub.1-C.sub.8 linear alkyl group, a C.sub.2-C.sub.8 linear alkenyl group, a C.sub.3-C.sub.8 linear, branched, or cyclic alkyl or alkenyl group, a C.sub.4-C.sub.8 linear, branched, or cyclic alkadienyl group, or a C.sub.3-6 aryl, C.sub.2-6 heterocyclic, or C.sub.6-8 arylalkyl group optionally substituted by a hydroxyl group, a C.sub.1-3 alkyl group, or a C.sub.1-3 alkoxy group.

5. The process according to claim 1, wherein R.sup.a and R.sup.b represent, independently from each other, a C.sub.3-6 heterocyclic group comprising from 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulphur.

6. The process according to claim 1, wherein the catalyst or the pre-catalyst is of formula
[Ru(PP)(NN).sub.n(RCOO).sub.2]  (1) wherein PP, NN, R, and n have the same meaning as defined in claim 1.

7. The process according to claim 6, wherein the RCOO group of (I) is selected from the group consisting of isobutyrate, pivalate, .sup.tBu-acetate, trifluoroacetate, 2-Et-hexanoate, cyclohexanecarboxylate, picolinate, cinnamate, benzoate, 4-Me-benzoate, 4-OMe-benzoate, 3,5-dichloro-benzoate, 2,4-dichloro-benzoate, isovalerate, adamantate, and sec-butyrate.

8. The process according to claim 1, wherein the bidentate NN ligand is a compound of formula ##STR00052## wherein a and a′, simultaneously or independently, represent 0 or 1, when a′ is 0 then the nitrogen atom is part of an aromatic heterocycle; the R.sup.1, taken separately, represent, simultaneously or independently, a hydrogen atom or a C.sub.1-6 linear, branched, or cyclic alkyl group optionally substituted or a phenyl or a benzyl group optionally substituted; two R.sup.1, taken together, may form a saturated heterocycle containing 3 to 7 atoms and including the atoms to which said le are bonded, said heterocycle being optionally substituted; R.sup.2 and R.sup.3, taken separately, represent, simultaneously or independently, a hydrogen atom, a C.sub.1-6 linear, branched alkyl group optionally substituted, or a C.sub.6-10 aromatic group optionally substituted; a R.sup.1 and an adjacent R.sup.2, taken together, may form a saturated or unsaturated heterocycle containing 5 to 8 atoms and including the atoms to which said R.sup.1 and R.sup.2 are bonded, and optionally containing one additional nitrogen or oxygen atom; two R.sup.2, taken together, may form a saturated or unsaturated ring having 5 to 8 atoms and including the carbon atoms to which said two R.sup.2 groups are bonded, said ring optionally containing one additional nitrogen and/or oxygen atom; and Q represents a group of formula ##STR00053## wherein m is 1 or 2, and R.sup.5 and R.sup.6 represent, simultaneously or independently, a hydrogen atom, a C.sub.1-6 linear, branched, or cyclic alkyl group optionally substituted or a C.sub.6-10 aromatic group optionally substituted; two distinct R.sup.6 and/or R.sup.5 groups, taken together, may form a C.sub.3-8 saturated ring optionally substituted, including the atoms to which said R.sup.6 and/or R.sup.5 groups are bonded, and optionally containing one or two additional nitrogen or oxygen atoms.

9. The process according to claim 8, wherein a is 0.

10. The process according to claim 8, wherein the bidendate (NN) ligand is selected from the group consisting of ethane-1,2-diamine, N,N-dimethylethane-1,2-diamine, N,N,N′,N′-tetramethylethane-1,2-diamine, 1,2-diphenylethane-1,2-diamine, (1R,2R)-1,2-diphenylethane-1,2-diamine, cyclohexane-1,2-diamine, (1R,2R)-cyclohexane-1,2-diamine, propane-1,3-diamine, and pyridin-2-ylmethanamine.

11. The process according to claim 1, wherein the bidentate ligand (PP) is a compound of formula ##STR00054## wherein R.sup.11 and R.sup.12, when taken separately, represent, simultaneously or independently, a C.sub.1-6 linear alkyl group optionally substituted, a C.sub.3-6 branched or cyclic alkyl group optionally substituted, or a C.sub.6-10 aromatic group optionally substituted; and Q′ represents a group of formula ##STR00055## wherein m′ is 1, 2, 3 or 4; and R.sup.5′ and R.sup.6′ represent, simultaneously or independently, a hydrogen atom, a C.sub.1-6 linear or branched alkyl group optionally substituted or a C.sub.6-10 aromatic group optionally substituted; two distinct R.sup.6′ and/or R.sup.5′ groups, taken together, may form a C.sub.3 to C.sub.8 saturated or unsaturated ring optionally substituted, including the atoms to which said R.sup.6′ and/or R.sup.5′ groups are bonded, and optionally containing one or two additional nitrogen or oxygen atoms; or a C.sub.10-C.sub.16 metallocenediyl, a 2,2′-diphenyl, a 1,1′-binaphthalene-2,2′-diyl, a benzenediyl, a naphthalenediyl, 2,3-bicyclo[2:2:1]hept-5-enediyl, 4,6-phenoxazinediyl, 4,5-(9, 9-dimethyl)-xanthenediyl, 4,6-10H-phenoxazinediyl, 2,2′-(oxybis(2, 1-phenylene)), or bis(phen-2-yl)ether group optionally substituted.

12. The process according to claim 11, wherein the R.sup.11 and R.sup.12, when taken separately, represent, simultaneously or independently, a C.sub.3-6 branched or cyclic alkyl group or a C.sub.6-10 aromatic group.

13. The process according to claim 11, wherein the Q′ represents a linear C.sub.1-4 alkanediyl radical, a 1,2- or 1,1′-C.sub.10-12 metallocenediyl, a 2,2′-diphenyl, a 1,2-benzenediyl, a 1,1′-binaphthalene-2,2′-diyl, or a 1,8- or 1,2-naphthalenediyl, 4,6-10H-phenoxazinediyl or 2,2′-(oxybis(2,1-phenylene)) group optionally substituted.

14. The process according to claim 11, wherein the (PP) ligand is selected from the group consisting of bis(dicyclohexylphosphanyl)methane, 1,2-bis(dicyclohexylphosphanyl)ethane, 1,2-bis(diphenylphosphanyl)ethane, 1,2-bis(diphenylphosphanyl)ethane, 1,3-bis(diisopropylphosphanyl)propane, 1,3-bis(dicyclohexylphosphanyl)propane, 1,4-bis(diphenylphosphanyl)butane, 1,1′-bis(diphenylphosphanyl)ferrocene, 1,1′-bis(dii sopropylphosphanyl)ferrocene, 1,1′-bis(dicyclohexylphosphanyl)ferrocene, 2,2′-bis(diphenylphosphaneyl)-1,1′-biphenyl, 2,2′-bis(dicyclohexylphosphaneyl)-1,1′-biphenyl, (oxybis(2,1-phenylene))bis(diphenylphosphane), and 4, 6-bis(diphenylphosphanyl)-10H-phenoxazine.

15. The process according to claim 1, wherein the complexes of formula (1) are generated directly in situ.

Description

EXAMPLES

(1) The invention will now be described in further detail by way of the following examples, wherein the temperatures are indicated in degrees centigrade and the abbreviations have the usual meaning in the art.

(2) All the procedures described hereafter have been carried out under an inert atmosphere unless stated otherwise. Hydrogenations were carried out in stainless steel autoclave. H.sub.2 gas (99.99990%) was used as received. NMR spectra were recorded on a Bruker AM-400 (.sup.1H at 400.1 MHz, .sup.13C {.sup.1H} at 100.6 MHz, and .sup.31P at 161.9 MHz) spectrometer and normally measured at 300 K, in CD.sub.2Cl.sub.2 unless indicated otherwise. Chemical shifts are listed in ppm.

Example 1

(3) Catalytic hydrogenation of imines using complex [Ru(OPiv).sub.2(PP)(en)] (OPiv=Pivalate, en=ethane-1,2-diamine) generated in-situ:

(4) General procedure for the catalytic hydrogenation of (E)-N-(1H-pyrazol-5-yl)-1-(thiophen-2-yl)methanimine as substrate:

(5) Under argon, a 10 ml vial was charged with [Ru(OPiv).sub.2(cod)].sub.2[H.sub.2O] (3.3 mg, 0.004 mmoles, 0.25 mol %) and the corresponding diphosphine (0.009 mmoles, 0.3 mol %) followed by EtOH (2 ml). The vial was sealed and heated in an aluminium block at 50° C. for 3h. Then the vial was brought back under argon, and a solution of ethylene diamine in EtOH (1 ml at 0.0125 M, 0.0125 mmoles, 0.4 mol %) was added. The vial was sealed and heated again at 67° C. for 2h. Then the solution was added under argon into a glass tube containing the imine (3 mmol), and the tube was placed in a Biotage Endeavour® multi-reactor. The tube was pressurised with hydrogen gas at 30 bar and heated at 100° C. with stirring (800 rpm). After 20 h, the system was cooled to room temperature and ventilated.

(6) Then, an aliquot (0.1 ml) was taken, diluted with CH.sub.2Cl.sub.2 (1 ml) and analysed by GC (HP-1).

(7) The results with various diphosphines taken from Table 2 are shown in Table 1.

(8) TABLE-US-00001 TABLE 1 Hydrogenation of (E)-N-(1H-pyrazol-5-yl)-1-(thiophen-2-yl)methanimine using [Ru(OPiv).sub.2(PP)(en)] generated in-situ: Test PP.sup.a) Ru.sup.b) Conv..sup.c) Amine.sup.d) 1 L1 1000 100 99 2 L1 500 60 40 3 L2 2500 100 99 4 L2 1000 100 96 5 L2 500 75 55 6 L3 2500 100 95 7 L3 1000 100 96 8 L3 500 100 93 9 L4 2500 100 93 10 L4 1000 100 96 11 L4 500 100 100 12 L5 2500 100 97 13 L5 1000 100 97 14 L5 500 100 92 15 L6 2500 100 95 16 L6 1000 100 97 17 L6 500 100 93 18 L7 2500 100 83 .sup.a)Diphosphines used as described in Table 2. .sup.b)Molar ratio in ppm of complex relative to the substrate. .sup.c)Conversion calculated according to amount of starting material left as measured by GC (HP-1). .sup.d)Amount of desired amine as measured by GC (HP-1).

(9) TABLE-US-00002 TABLE 2 Structure and names of diphosphines used Ligand Structure Name L1 0 bis(dicyclohexylphosphanyl)methane L2 1,2-bis(dicyclohexylphosphanyl)ethane L3 1,2-bis(diphenylphosphanyl)ethane L4 1,3-bis(diisopropylphosphanyl)propane L5 1,4-bis(diphenylphosphanyl)butane L6 1,1′-bis(diphenylphosphanyl)ferrocene L7 (oxybis(2,1-phenylene))bis(diphenylphosphane) L8 1,3-bis(dicyclohexylphosphanyl)propane

Example 2

(10) Catalytic hydrogenation of imines using complex [Ru(OPiv).sub.2(PP)(NN)] (OPiv=Pivalate) generated in-situ:

(11) General procedure for the catalytic hydrogenation of (E)-N-(1H-pyrazol-5-yl)-1-(thiophen-2-yl)methanimine as substrate:

(12) Under argon, a 10 ml vial was charged with the preformed [Ru(OPiv).sub.2(L4)] (4.5 mg, 0.006 mmoles) followed by a solution of the corresponding diamine in EtOH (1 ml at 0.07 M, 0.007 mmoles). More EtOH (1 ml) was added and the vial was sealed and heated in an aluminium block at 60° C. for 1.5h. Then a part (0.2 ml, 0.0006 mmoles, 0.02 mol %) of this solution was added to a glass tube containing the imine (3 mmol). More EtOH (2.8 ml) was added and the tube was placed in a Biotage Endeavour® multi-reactor. The tube was pressurised with hydrogen gas at 30 bar and heated at 100° C. with stirring (800 rpm). After 16 hours, the system was cooled to room temperature and ventilated. Then, an aliquot (0.1 ml) was taken, diluted with CH.sub.2Cl.sub.2 (1 ml) and analysed by GC (HP-1). The results with various ruthenium complexes and various diamines taken from Table 4 are shown in Table 3.

(13) TABLE-US-00003 TABLE 3 Hydrogenation of (E)-N-(1H-pyrazol-5-yl)-1-(thiophen-2-yl)methanimine using [Ru(OPiv).sub.2(PP)(NN)] generated in-situ: Test PP.sup.a) NN.sup.b) Ru.sup.c) Conv..sup.d) Amine.sup.e) 1 L3 N1 200 100 89 2 L3 N2 200 100 95 3 L3 N3 200 100 84 4 L3 N4 200 96 76 5 L3 N5 200 100 89 6 L3 N6 200 79 56 7 L3 N7 200 100 94 8 L4 N1 200 100 99 9 L4 N2 200 100 97 10 L4 N3 200 100 97 11 L4 N4 200 100 98 12 L4 N5 200 100 98 13 L4 N6 200 99 97 14 L4 N7 200 99 95 .sup.a)Diphosphines used as described in Table 2. .sup.b)Diamines used as described in Table 4. .sup.c)Molar ratio in ppm of complex relative to the substrate. .sup.d)Conversion calculated according to amount of starting material left as measured by GC (HP-1). .sup.e)Amount of desired amine as measured by GC (HP-1).

(14) TABLE-US-00004 TABLE 4 Structure and names of diamines used. Ligand Structure Name N1 ethane-1,2-diamine N2 N,N-dimethylethane- 1,2-diamine N3 0 N,N,N′,N′-tetramethylethane- 1,2-diamine N4 (1R,2R)-1,2-diphenylethane- 1,2-diamine N5 (1R,2R)-cyclohexane- 1,2-diamine N6 pyridin-2-ylmethanamine N7 propane-1,3-diamine

Example 3

(15) Catalytic hydrogenation of imines using complex [Ru(OPiv).sub.2(L4)(N1)] (OPiv=Pivalate):

(16) General procedure for the catalytic hydrogenation of (E)-N-(1H-pyrazol-5-yl)-1-(thiophen-2-yl)methanimine as substrate:

(17) A 500 ml stainless steel autoclave was charged with preformed [Ru(OPiv).sub.2(L4)(N1)] (18.6 mg, 0.029 mmoles), (E)-N-(1H-pyrazol-5-yl)-1-(thiophen-2-yl)methanimine (25.2 g, 142 mmoles) and absolute EtOH (88.2 g). The autoclave was closed, purged with hydrogen gas (5×10 bar) and then pressurized at 15 bar. The reaction was stirred (800 rpm) and heated at 100° C. After 7.5 h the autoclave was cooled to room temperature. The reaction mixture was removed from the autoclave and some EtOH was added to rinse the autoclave. A sample (10.9 g) of the reaction mixture (137.7 g) was concentrated under vacuum (35 mbar/40° C.) to give a brown oil (2.42 g), which was distilled on a Kugel-Rohr (0.4 mbar/208-224° C.) to give a colourless oil (1.93 g) with some residue left (0.15 g), which corresponded to an extrapolated yield of 96%.

(18) The results at various temperature and hydrogen gas pressure are shown in Table 5.

(19) TABLE-US-00005 TABLE 5 Hydrogenation of (E)-N-(1H-pyrazol-5-yl)-1-(thiophen- 2-yl)methanimine using preformed [Ru(OPiv).sub.2(L4)(N1)] complexes at various temperature and pressure: Test T[° C.] H.sub.2 [bar] Ru.sup.a) Time [h] Conv..sup.b) Amine.sup.c) Yield.sup.d) 1 100 15 200 7.5 100 99 96 2 100 26 200 8 100 99 — 3 90 15 200 10.5 99.5 97 96 4 110 15 200 5.5 100 96 — .sup.a)Molar ratio in ppm of complex relative to the substrate. .sup.b)Conversion calculated according to amount of starting material left as measured by GC (HP-1). .sup.c)Amount of desired amine as measured by GC (HP-1). .sup.d)Isolated yield after distillation.

Example 4

(20) Catalytic hydrogenation of imines using complex [Ru(OPiv).sub.2(L4)] (OPiv=Pivalate):

(21) General procedure for the catalytic hydrogenation of (E)-N-(1H-pyrazol-5-yl)-1-(thiophen-2-yl)methanimine as substrate:

(22) A 500 ml stainless steel autoclave was charged with preformed [Ru(OPiv).sub.2(L4)] (34.1 mg, 0.059 mmoles), (E)-N-(1H-pyrazol-5-yl)-1-(thiophen-2-yl)methanimine (50.5 g, 285 mmoles) and absolute EtOH (175.1 g). The autoclave was closed, purged with hydrogen gas (5×10 bar) and then pressurized at 25 bar. The reaction was stirred (800 rpm) and heated at 100° C. After 8 h the autoclave was cooled to room temperature. The reaction mixture was removed from the autoclave and some EtOH was added to rinse the autoclave. A sample (10.6 g) of the reaction mixture (259.6 g) was concentrated under vacuum (20 mbar/40° C.) to give a brown oil (2.31 g), which was distilled on a Kugel-Rohr (0.2 mbar/180-215° C.) to give a colourless oil (1.93 g) with some residue left (0.12 g), which corresponded to an extrapolated yield of 92%.

Example 5

(23) Catalytic Hydrogenation of imines using Complex [Ru(OPiv).sub.2(L4)(N1)] (OPiv=Pivalate):

(24) General procedure for the catalytic hydrogenation of various imines taken from Table 6. A glass tube is charged with [Ru(OPiv).sub.2(L4)(N1)] (9.9 mg, 0.015 mmoles, 0.5 mol %), (E)-N-(4-methoxyphenethyl)-1-(thiophen-2-yl)methanimine (738.8 mg, 3 mmoles) and absolute EtOH (3 ml). The tube was then placed in a Biotage Endeavour® multi-reactor, and pressurised with hydrogen gas at 15 bar and heated at 100° C. with stirring (800 rpm). After 16 h, the system was cooled to room temperature and ventilated. Then, an aliquot (0.1 ml) was taken, diluted with CH.sub.2Cl.sub.2 (1 ml) and analysed by GC (HP-1). Purification by column chromatography (SiO.sub.2, CH.sub.2Cl.sub.2/Et.sub.2O 4/1+Et.sub.3N 1%) gave the desired product (500 mg, 1.99 mmoles, 66%).

(25) Using these conditions several imines described in Table 6 were hydrogenated and the results are shown in Table 7.

(26) TABLE-US-00006 TABLE 6 Structure and names of imines hydrogenated. Ligand Structure Name S1 (E)-N-(1H-pyrazol-5-yl)-1- (thiophen-2-yl)methanimine S2 (E)-N-(4-methoxyphenethyl)-1- (thiophen-2-yl)methanimine S3 (E)-N-benzyl-1-(thiophen- 2-yl)methanimine S4 (E)-N-benzyl-1-(p-tolyl)methanimine S5 (E)-N-benzyl-1-(2- methoxyphenyl)methanimine S6 0 (E)-N-(1H-pyrazol-5-yl)-1- (p-tolyl)methanimine

(27) TABLE-US-00007 TABLE 7 Hydrogenation of imines described in Table 6 using [Ru(OPiv).sub.2(L4)(N1)]: Test Imines Ru.sup.a) Conv..sup.b) Amine.sup.c) Yield.sup.d) 1 S2 5000 99 85 66 2 S3 5000 89 74 64 3 S4 5000 98 84 79 4 S5 5000 95 77 68  5.sup.e) S6 5000 100 91 76 .sup.a)Molar ratio in ppm of complex relative to the substrate. .sup.b)Conversion calculated according to the amount of starting material left as measured by GC (HP-1). .sup.c)Amount of desired amine as measured by GC (HP-1). .sup.d)Isolated yield after purification. .sup.e)Test performed in THF.

Example 6

(28) Comparative Example—Catalytic Hydrogenation of imines using Complex [Ru(bis(2-(diphenylphosphaneyflethyl)amine)(CO)(H)(BH.sub.4)]:

(29) General procedure for the catalytic hydrogenation of (E)-N-(1H-pyrazol-5-yl)-1-(thiophen-2-yl)methanimine as substrate in various solvents:

(30) Under argon, a 10 ml tube was charged with [Ru(bis(2-(diphenylphosphaneyl)ethyDamine)(CO)(H)(BH.sub.4)] (12.9 mg, 0.022 mmoles, 1.1 mol %), (E)-N-(1H-pyrazol-5-yl)-1-(thiophen-2-yl)methanimine (355.6 mg, 2.01 moles) and THF (3 ml). The tube was placed in a Biotage Endeavour® multi-reactor. The tube was pressurised with hydrogen gas at 20 bar and heated at 100° C. with stirring (800 rpm). After 20 h, the system was cooled to room temperature and ventilated. Then, an aliquot (0.1 ml) was taken, diluted with CH.sub.2Cl.sub.2 (1 ml) and analysed by GC (HP-1). The results with various solvents are shown in Table 8.

(31) TABLE-US-00008 TABLE 8 Hydrogenation of (E)-N-(1H-pyrazol-5-yl)- 1-(thiophen-2-yl)methanimine using [Ru(bis(2- (diphenylphosphaneyl)ethyl)amine)(CO)(H)(BH.sub.4)] in various solvent: Test Solvent Conv..sup.a) Amine.sup.b) 1 THF 6 2 2 Toluene 13 3 3 MTBE 12 3 4 iPrOH 6 6 5 EtOH 8 (20.sup.c)) 7 (13.sup.c)) 6 MeOH 10 6 .sub.a)Conversion calculated according to the amount of starting material left as measured by GC (HP-1). .sub.b)Amount of desired amine as measured by GC (HP-1). .sub.c)Test performed with H.sub.2 (80 bar) at 100° C. for 20 h.

Example 7

(32) Catalytic Hydrogenation of imines using Complex [Ru(OPiv).sub.2(L8)] (OPiv=Pivalate):

(33) General procedure for the catalytic hydrogenation of various imines taken from Table 9. A stainless steel autoclave of 60 ml is charged with [Ru(OPiv).sub.2(L8)] (40.4 mg, 0.055 mmoles, 0.5 mol %), (E)-N-phenyl-1-(2-thienyl)methanimine (2.048 g, 10.94 mmoles) and MeOH (9 ml). The autoclave was closed and pressurised with hydrogen gas at 50 bar and heated at 100° C. with stirring (800 rpm). After 26 h, the system was cooled to room temperature and ventilated. Then, the reaction mixture was concentrated under vacuum (40° C./5 mbar) to give a brown oil (2.089 g). Analysis by .sup.1H-NMR showed complete conversion. Purification by Kugel-Rohr distillation (bp: 160-170° C./0.4 mbar) gave a white solid (1.855 g, GC (HP-1): 99.5%, 89% yield).

(34) Using these conditions several imines described in Table 9 were hydrogenated and the results are shown in Table 10.

(35) TABLE-US-00009 TABLE 9 Structure and names of imines hydrogenated. Ligand Structure Name S7 (E)-N-phenyl-1-(thiophen- 2-yl)methanimine S8 (E)-N-benzyl-1-(thiophen- 2-yl)methanimine S9 (E)-N-phenyl-1-(p-tolyl)methanimine S10 (E)-N-(4-methoxyphenyl)-1- phenylmethanimine S11 (E)-N-cyclohexyl-1- (p-tolyl)methanimine S12 (E)-N-(4-fluorophenyl)-1- (p-tolyl)methanimine S13 (E)-N-(4-methoxyphenyl)-1- (p-tolyl)methanimine S14 (E)-N-(2,4-dimethylphenyl)-1- (p-tolyl)methanimine S15 (E)-N-(pyridin-4-ylmethyl)-1- (p-tolyl)methanimine S16 0 (E)-1-(thiophen-2-yl)-N- (thiophen-2-ylmethyl)methanimine

(36) TABLE-US-00010 TABLE 10 Hydrogenation of imines described in Table 9 using [Ru(OPiv).sub.2(L8)]: Test Imines Ru.sup.a) Time (h) Conv..sup.b) Yield.sup.c) 1 S7 5000 26 100 89 2 S8 5000 24 100 90 3 S9 5000 38.5 100 97 4 S10 5000 38.5 100 90 5 S11 5000 24 100 93 6 S4 5000 24 100 89 7 S12 5000 24 100 97 8 S13 5000 24.5 100 96 9 S14 5000 25 100 88 10 S15 5000 24 100 70 11 S16 5000 24 100 83 .sup.a)Molar ratio in ppm of complex relative to the substrate. .sup.b)Conversion calculated according to the amount of starting material left as measured by GC (HP-1) in the crude reaction mixture. .sup.c)Isolated yield after Kugel-Rohr distillation of the desired amine.

Example 8

(37) Comparative Example—Catalytic Hydrogenation of (E)-N-(1H-pyrazol-5-yl)-1-(thiophen-2-yl)methanimine as Substrate using Various ruthenium Complexes with and without Base

(38) General Procedure for the Catalytic Hydrogenation:

(39) A 10 ml glass tube was charged with [Ru(OPiv).sub.2(L3)(N4)] (1.4 mg, 0.015 mmoles, 0.1 mol %), (E)-N-(1H-pyrazol-5-yl)-1-(thiophen-2-yl)methanimine (266.6 mg, 1.5 mmoles) and absolute EtOH (3 ml). The tube was then placed in a Biotage Endeavour® multi-reactor, and pressurised with hydrogen gas at 10 bar and then heated at 100° C. with stirring (800 rpm). After 12 h, the system was cooled to room temperature and ventilated. Then, an aliquot (0.1 ml) was taken, diluted with CH.sub.2Cl.sub.2 (1 ml) and analysed by GC (HP-1). Using these conditions several ruthenium complexes were compared and the results are shown in Table 11.

(40) TABLE-US-00011 TABLE 11 Hydrogenation of (E)-N-(1H-pyrazol-5-yl)-1-(thiophen-2-yl)methanimine using various ruthenium complexes in ethanol: Base Test Ruthenium complexes (mol %) Conv..sup.a) Amine.sup.b) 1 [Ru(OPiv).sub.2(L3)(N4)] — 27 23 2 [Ru(Cl).sub.2(L3)(N4)].sup.c) tBuOK (10) 3 1 .sup.a)Conversion calculated according to the amount of starting material left as measured by GC (HP-1). .sup.b)Amount of desired amine as measured by GC (HP-1). .sup.c)Comparative example; complex not part of the invention

(41) When the hydrogenation was carried out with [Ru(C1).sub.2(L3)(N4)] in a presence of base, as reported in prior art, only 1% of amine was detected after 12h (Table 11, entry 2). In the same conditions, with the invention's complex, 23% of amine was detected (Table 11, entry 1). The hydrogenation of the present invention allows improving the hydrogenation of amine.