WO2024047674A1 - Manganese based catalyst, its process of preparation and their use in process of hydrogenation reactions - Google Patents
Manganese based catalyst, its process of preparation and their use in process of hydrogenation reactions Download PDFInfo
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- WO2024047674A1 WO2024047674A1 PCT/IN2023/050826 IN2023050826W WO2024047674A1 WO 2024047674 A1 WO2024047674 A1 WO 2024047674A1 IN 2023050826 W IN2023050826 W IN 2023050826W WO 2024047674 A1 WO2024047674 A1 WO 2024047674A1
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- WIPO (PCT)
- Prior art keywords
- alkyl
- aryl
- formula
- group
- substituted
- Prior art date
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- 239000011572 manganese Substances 0.000 title claims abstract description 78
- 239000003054 catalyst Substances 0.000 title claims abstract description 66
- 238000005984 hydrogenation reaction Methods 0.000 title claims abstract description 55
- 238000000034 method Methods 0.000 title claims abstract description 49
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 title claims abstract description 40
- 229910052748 manganese Inorganic materials 0.000 title claims abstract description 40
- 230000008569 process Effects 0.000 title claims abstract description 36
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 150000002576 ketones Chemical class 0.000 claims abstract description 39
- 239000000758 substrate Substances 0.000 claims abstract description 37
- 150000001299 aldehydes Chemical class 0.000 claims abstract description 29
- 150000002466 imines Chemical class 0.000 claims abstract description 28
- -1 tetrafluoroborate Chemical group 0.000 claims description 123
- 125000000217 alkyl group Chemical group 0.000 claims description 79
- 125000003118 aryl group Chemical group 0.000 claims description 76
- 125000001072 heteroaryl group Chemical group 0.000 claims description 53
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 43
- 150000001875 compounds Chemical class 0.000 claims description 39
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 34
- 125000001424 substituent group Chemical group 0.000 claims description 32
- 239000001257 hydrogen Substances 0.000 claims description 31
- 229910052739 hydrogen Inorganic materials 0.000 claims description 31
- 238000006243 chemical reaction Methods 0.000 claims description 29
- 125000004122 cyclic group Chemical group 0.000 claims description 28
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 25
- 239000011541 reaction mixture Substances 0.000 claims description 22
- 125000003545 alkoxy group Chemical group 0.000 claims description 20
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 19
- 150000001336 alkenes Chemical class 0.000 claims description 19
- 229910052736 halogen Inorganic materials 0.000 claims description 19
- 150000002367 halogens Chemical group 0.000 claims description 19
- 125000003107 substituted aryl group Chemical group 0.000 claims description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
- 239000003446 ligand Substances 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 18
- 239000002904 solvent Substances 0.000 claims description 18
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 18
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 17
- 150000001345 alkine derivatives Chemical class 0.000 claims description 14
- 229920006395 saturated elastomer Polymers 0.000 claims description 14
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- 238000003756 stirring Methods 0.000 claims description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 11
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 10
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 10
- 238000004440 column chromatography Methods 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 claims description 10
- 239000000741 silica gel Substances 0.000 claims description 10
- 229910002027 silica gel Inorganic materials 0.000 claims description 10
- 229910000404 tripotassium phosphate Inorganic materials 0.000 claims description 10
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- FCBMAOCCCGSEKV-UHFFFAOYSA-N n-ditert-butylphosphanyl-6-pyrazol-1-ylpyridin-2-amine Chemical compound CC(C)(C)P(C(C)(C)C)NC1=CC=CC(N2N=CC=C2)=N1 FCBMAOCCCGSEKV-UHFFFAOYSA-N 0.000 claims description 9
- 238000000746 purification Methods 0.000 claims description 9
- 235000019798 tripotassium phosphate Nutrition 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- 239000012298 atmosphere Substances 0.000 claims description 7
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 6
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 6
- 125000003282 alkyl amino group Chemical group 0.000 claims description 6
- 150000005215 alkyl ethers Chemical group 0.000 claims description 6
- 125000001769 aryl amino group Chemical group 0.000 claims description 6
- 150000008378 aryl ethers Chemical group 0.000 claims description 6
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical group FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 claims description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
- 125000004043 oxo group Chemical group O=* 0.000 claims description 6
- 239000002798 polar solvent Substances 0.000 claims description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 6
- 150000001298 alcohols Chemical class 0.000 claims description 5
- 150000001346 alkyl aryl ethers Chemical class 0.000 claims description 5
- 239000012300 argon atmosphere Substances 0.000 claims description 5
- JWHAUXFOSRPERK-UHFFFAOYSA-N propafenone Chemical compound CCCNCC(O)COC1=CC=CC=C1C(=O)CCC1=CC=CC=C1 JWHAUXFOSRPERK-UHFFFAOYSA-N 0.000 claims description 5
- 125000005157 alkyl carboxy group Chemical group 0.000 claims description 4
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 4
- 239000007789 gas Substances 0.000 claims description 4
- 150000004820 halides Chemical group 0.000 claims description 4
- 230000003647 oxidation Effects 0.000 claims description 4
- 238000007254 oxidation reaction Methods 0.000 claims description 4
- 229910015900 BF3 Inorganic materials 0.000 claims description 3
- WAEMQWOKJMHJLA-UHFFFAOYSA-N Manganese(2+) Chemical compound [Mn+2] WAEMQWOKJMHJLA-UHFFFAOYSA-N 0.000 claims description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 3
- 125000001931 aliphatic group Chemical group 0.000 claims description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 3
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 claims description 3
- 239000000920 calcium hydroxide Substances 0.000 claims description 3
- 229910001861 calcium hydroxide Inorganic materials 0.000 claims description 3
- 235000011116 calcium hydroxide Nutrition 0.000 claims description 3
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 claims description 3
- 229910052808 lithium carbonate Inorganic materials 0.000 claims description 3
- HQRPHMAXFVUBJX-UHFFFAOYSA-M lithium;hydrogen carbonate Chemical compound [Li+].OC([O-])=O HQRPHMAXFVUBJX-UHFFFAOYSA-M 0.000 claims description 3
- 229910001437 manganese ion Inorganic materials 0.000 claims description 3
- XYFCBTPGUUZFHI-UHFFFAOYSA-N phosphine group Chemical group P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 3
- 239000011736 potassium bicarbonate Substances 0.000 claims description 3
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 3
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- 235000011181 potassium carbonates Nutrition 0.000 claims description 3
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 3
- 235000011118 potassium hydroxide Nutrition 0.000 claims description 3
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 3
- 235000011009 potassium phosphates Nutrition 0.000 claims description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical compound [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 claims description 3
- 150000003512 tertiary amines Chemical class 0.000 claims description 3
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 3
- 238000013022 venting Methods 0.000 claims description 3
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 2
- 239000004210 ether based solvent Substances 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 33
- 229910052799 carbon Inorganic materials 0.000 description 32
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 26
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 23
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 125000003342 alkenyl group Chemical group 0.000 description 20
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 16
- 125000000304 alkynyl group Chemical group 0.000 description 16
- 230000015572 biosynthetic process Effects 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
- 229910052760 oxygen Inorganic materials 0.000 description 14
- 238000003786 synthesis reaction Methods 0.000 description 14
- 125000004429 atom Chemical group 0.000 description 13
- 238000004009 13C{1H}-NMR spectroscopy Methods 0.000 description 12
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 12
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- 235000019439 ethyl acetate Nutrition 0.000 description 10
- 125000005843 halogen group Chemical group 0.000 description 10
- 125000005842 heteroatom Chemical group 0.000 description 10
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 9
- 239000003208 petroleum Substances 0.000 description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 125000000623 heterocyclic group Chemical group 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 229910052717 sulfur Inorganic materials 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-MZWXYZOWSA-N benzene-d6 Chemical compound [2H]C1=C([2H])C([2H])=C([2H])C([2H])=C1[2H] UHOVQNZJYSORNB-MZWXYZOWSA-N 0.000 description 6
- 238000012512 characterization method Methods 0.000 description 6
- 150000002825 nitriles Chemical class 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 238000005899 aromatization reaction Methods 0.000 description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 4
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 229910018385 Mn(CO)5 Inorganic materials 0.000 description 4
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 4
- QGGZBXOADPVUPN-UHFFFAOYSA-N dihydrochalcone Chemical compound C=1C=CC=CC=1C(=O)CCC1=CC=CC=C1 QGGZBXOADPVUPN-UHFFFAOYSA-N 0.000 description 4
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 4
- 125000003709 fluoroalkyl group Chemical group 0.000 description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 description 4
- 229910052698 phosphorus Inorganic materials 0.000 description 4
- 238000000607 proton-decoupled 31P nuclear magnetic resonance spectroscopy Methods 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 125000004076 pyridyl group Chemical group 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 125000000335 thiazolyl group Chemical group 0.000 description 4
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 4
- 238000004679 31P NMR spectroscopy Methods 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 125000002947 alkylene group Chemical group 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 150000001721 carbon Chemical group 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 150000002118 epoxides Chemical class 0.000 description 3
- 125000001033 ether group Chemical group 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 125000002541 furyl group Chemical group 0.000 description 3
- 125000004438 haloalkoxy group Chemical group 0.000 description 3
- 125000001188 haloalkyl group Chemical group 0.000 description 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 3
- 125000002883 imidazolyl group Chemical group 0.000 description 3
- 125000000842 isoxazolyl group Chemical group 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 125000002950 monocyclic group Chemical group 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 125000003373 pyrazinyl group Chemical group 0.000 description 3
- 125000003226 pyrazolyl group Chemical group 0.000 description 3
- 125000002098 pyridazinyl group Chemical group 0.000 description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 description 3
- 125000000168 pyrrolyl group Chemical group 0.000 description 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 229910052710 silicon Inorganic materials 0.000 description 3
- 125000000547 substituted alkyl group Chemical group 0.000 description 3
- 125000001113 thiadiazolyl group Chemical group 0.000 description 3
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- 125000001425 triazolyl group Chemical group 0.000 description 3
- 125000004417 unsaturated alkyl group Chemical group 0.000 description 3
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- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 2
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- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 2
- MALLEZRHGUJEJP-UHFFFAOYSA-N 6-pyrazol-1-ylpyridin-2-amine Chemical compound NC1=CC=CC(N2N=CC=C2)=N1 MALLEZRHGUJEJP-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
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- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 2
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- 238000005481 NMR spectroscopy Methods 0.000 description 2
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- 125000002619 bicyclic group Chemical group 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 238000010531 catalytic reduction reaction Methods 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
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- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 2
- YMWUJEATGCHHMB-DICFDUPASA-N dichloromethane-d2 Chemical compound [2H]C([2H])(Cl)Cl YMWUJEATGCHHMB-DICFDUPASA-N 0.000 description 2
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 2
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 description 2
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- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 125000003838 furazanyl group Chemical group 0.000 description 2
- 125000004404 heteroalkyl group Chemical group 0.000 description 2
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 2
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- 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
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- DQFBYFPFKXHELB-VAWYXSNFSA-N trans-chalcone Chemical compound C=1C=CC=CC=1C(=O)\C=C\C1=CC=CC=C1 DQFBYFPFKXHELB-VAWYXSNFSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/26—Catalysts comprising hydrides, coordination complexes or organic compounds containing in addition, inorganic metal compounds not provided for in groups B01J31/02 - B01J31/24
- B01J31/32—Catalysts comprising hydrides, coordination complexes or organic compounds containing in addition, inorganic metal compounds not provided for in groups B01J31/02 - B01J31/24 of manganese, technetium or rhenium
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B35/00—Reactions without formation or introduction of functional groups containing hetero atoms, involving a change in the type of bonding between two carbon atoms already directly linked
- C07B35/02—Reduction
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B41/00—Formation or introduction of functional groups containing oxygen
- C07B41/02—Formation or introduction of functional groups containing oxygen of hydroxy or O-metal groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B43/00—Formation or introduction of functional groups containing nitrogen
- C07B43/04—Formation or introduction of functional groups containing nitrogen of amino groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
- C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
- C07C29/143—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of ketones
- C07C29/145—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of ketones with hydrogen or hydrogen-containing gases
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/62—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by hydrogenation of carbon-to-carbon double or triple bonds
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F13/00—Compounds containing elements of Groups 7 or 17 of the Periodic Table
- C07F13/005—Compounds without a metal-carbon linkage
Definitions
- the present invention provides a novel manganese based catalyst of Formula I, its process of preparation, and their use in a process of hydrogenation of different substrates. More particularly, the present invention provides a process of hydrogenation where the novel manganese catalyst of Formula I is used for hydrogenation of various substrates of Formula IIA or IIB such as ⁇ , ⁇ -unsaturated ketones, aldehydes, imines, etc.
- metal ⁇ ligand bifunctional catalysis metal ⁇ ligand cooperation
- complexes contain electronically coupled hydride and acidic hydrogen atoms.
- metal ⁇ ligand cooperation An effective way of bond activation by metal ⁇ ligand cooperation involves aromatization/dearomatization of the ligand in pincer complexes in which a central pyridine-based backbone is connected with ⁇ CH 2 PR 2 and/or ⁇ CH 2 NR 2 substituents. This has resulted in the development of novel and unprecedented iron and manganese catalysis, where this type of cooperation plays a key role in the heterolytic cleavage of H2.
- reaction conditions are very harsh to achieve the hydrogenation of alkenes and nitriles.
- Manganese catalysts and their use in hydrogenation of ketones is disclosed in the US patent application number ‘US2022119329A1’ wherein hydrogenation of ketones involves higher pressure and temperature conditions. Chemo- and regioselective hydrogenation of alkenes and carbonyls under mild conditions is crucial to achieve sustainable synthesis.
- Most of the known catalysts for hydrogenation of various substrates such as ⁇ , ⁇ -unsaturated ketones, aldehydes and imines requires expensive catalysts and/or harsh reaction conditions (high H 2 pressure and high reaction temperature).
- the main objective of the present invention is to provide a novel manganese catalyst of Formula I, for a catalytic hydrogenation processes. Another objective of the present invention is to provide a process of preparation of said manganese based catalyst of formula I. Yet another objective of the present invention is to provide a process for hydrogenation of various substrates such as ⁇ , ⁇ -unsaturated ketones, aldehydes and imines by using said manganese catalyst (of Formula I).
- Fig 1 The synthetic scheme explaining general process of hydrogenation of substrates such as ⁇ , ⁇ -unsaturated ketones, aldehydes and imines by using the manganese catalyst (of Formula I).
- Fig 2 The synthetic scheme explaining process of preparation of the manganese based catalyst of formula I.
- Fig 3 ORTEP (Oak Ridge Thermal-Ellipsoid Plot Program) of compound Mn-2 showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.
- Fig 5 Product Scope and Scheme of Mn-Catalyzed Hydrogenation of Aldehydes and Imines ( a Reaction Conditions: Substrate (0.20 mmol), Mn-3 (0.005 g, 0.01 mmol, 5 mol%), K 3 PO 4 (0.0043 g, 0.02 mmol), H 2 (5 bar), MeOH (1.0 mL). Yield of isolated compounds. b Obtained as a mixture of E and Z isomers. c Mixture of MeOH:DCM (4:1) used. c Reaction performed 50 o C).
- the present invention provides a novel manganese catalyst of Formula I or its isomeric forms, for hydrogenation of various substrates such as ⁇ , ⁇ -unsaturated ketones, aldehydes, and imines (of Formula IIA or IIB):
- Mn is manganese atom or manganese ion in oxidation state (I)
- moieties attached to Mn are selected from heteroaryl groups of pyridine and diazole, one or more carbon monoxide groups, and -PR 3 R 4 -NR 2 , wherein said nitrogen of -PR 3 R 4 -NR 2 is attached to said heteroaryl, and X group
- R 1 is selected from the group consisting of hydrogen, alkyl, aryl, alkylaryl, alkoxy, cycloalkyl, alkyl cycloalkyl, and alkylcarboxy
- R 2 is selected from the group consisting of hydrogen, and alkyl
- R 3 is selected from the group consisting
- the present disclosure also provides a process of preparation of a novel manganese catalyst (Formula I) under mild conditions which comprises reacting compound of formula III with substituted pentacarbonylmanganese [Mn(CO) 5 X] at room temperature of 25 to 30 o C to yield a novel manganese catalyst (Formula I), Formula III wherein R 1 , R 2 , R 3 , R 4 and X are same as defined above under formula I.
- the present invention relates to a process of preparation of the manganese based catalyst complex of Formula I, the process comprising steps of: a) reacting a ligand compound of formula III with substituted pentacarbonylmanganese [Mn(CO)5X] with a solvent in a container to obtain a reaction mixture Formula III wherein R 1 , R 2 , R 3 , R 4 and X are same as defined above under formula I; b) stirring the reaction mixture of step a) under inert atmosphere at a temperature in the range of 27-80 o C for a time period of up to 48 hrs; c) purifying the mixture of step b) to obtain the manganese catalyst of Formula I.
- the ligand compound of formula III used in step a) is selected from N-(diphenylphosphaneyl)-6-(1H-pyrazol-1-yl)pyridin-2-amine (L1), N-(di-n- propylphosphaneyl)-6-(1H-pyrazol-1-yl)pyridin-2-amine (L2), N-(di-tert- butylphosphaneyl)-6-(1H-pyrazol-1-yl)pyridin-2-amine (L3) and N-(di-tert- butylphosphaneyl)-N-methyl-6-(1H-pyrazol-1-yl)pyridin-2-amine (L4).
- the solvent used in step a) is selected from tetrahydrofuran, 2-methyl tetrahydrofuran and toluene.
- the present invention provides a process for hydrogenation of substrate selected from ⁇ , ⁇ -unsaturated ketone, aldehyde and imine (of Formula IIA or IIB), by using the manganese based catalyst complex of Formula I, the process comprising steps of: (i) preparing a mixture of the substrate of Formula IIA or IIB in presence of Mn-catalyst of Formula I and a base in dry vial with stir bar Formula IIA Formula IIB; wherein A, B, Y and X of formula IIA and R1, R2 and R3 of formula IIB is same as defined under formulas IVA and IVB; (ii) transferring the reaction vial of step i) in an autoclave under argon atmosphere; (iii) adding a polar solvent in vial of step ii) and pressurizing the autoclave
- the novel hydrogenated compounds of formula IVA and/or IVB are selected from the group consisting of: (i) 1-(3-(Allyloxy)phenyl)-3-phenylpropan-1-one (2a) , (ii) 3-Phenyl-1-(3-(prop-2-yn-1-yloxy)phenyl)propan-1-one (2b) (iii) 1-(3-(Oxiran-2-ylmethoxy)phenyl)-3-phenylpropan-1-one (2c) (iv) 2-(4-Acetylphenoxy)-1,3-diphenylpropan-1-one (2d) .
- the base used in said hydrogenation process is selected from the group consisting of potassium carbonate, potassium phosphate, potassium hydroxide, tripotassium phosphate potassium tert-butoxide, sodium tert-butoxide, sodium carbonate, cesium carbonate, sodium hydroxide, lithium carbonate, lithium hydroxide, calcium hydroxide, potassium bicarbonate, sodium bicarbonate, sodium methoxide, lithium bicarbonate and tertiary amines.
- the polar solvent used in said hydrogenation process is selected from simple alcohols, such as C1-10 hydrocarbyl alcohol, saturated aliphatic C1-8alcohol, polyvalent alcohol; ether based solvent, aliphatic or aromatic hydrocarbon solvent, and halogenated hydrocarbon solvent, or mixtures thereof.
- the purification of step v) of said hydrogenation process is done by concentrating the crude hydrogenated compound and subjecting it to column chromatography on silica gel wherein petroleum ether and ethyl acetate is used as solvent media in a ratio of 70:1 respectively, for separation and purification, to yield desired hydrogenated compounds of formula IVA or IVB.
- Alkyl as used herein is collection of carbon atoms that are covalently linked together in normal, secondary, tertiary or cyclic arrangements, i.e., in linear, branched, cyclic arrangement or some combination thereof.
- An alkyl substituent to structure is chain of carbon atoms that is covalently attached to structure through sp 3 carbon of substituent.
- alkyl substituents contains one or more saturated moieties or groups and may additionally contain unsaturated alkyl moieties or groups, i.e., substituent may comprise one, two, three or more independently selected double bonds or triple bonds of combination thereof, typically one double or one triple bond if such unsaturated alkyl moieties or groups are present.
- Unsaturated alkyl moieties or groups include moieties or groups as described below for alkenyl, alkynyl, cycloalkyl, and aryl moieties.
- Saturated alkyl moieties contain saturated carbon atoms (sp 3 ) and no aromatic, sp 2 or sp carbon atoms.
- the number of carbon atoms in an alkyl moiety or group can vary and typically is 1 to about 50, e.g., about 1-30 or about 1-20, unless otherwise specified, e.g., C1-8 alkyl or C1-C8 alkyl means an alkyl moiety containing 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms and C 1-6 alkyl or C 1 -C 6 means an alkyl moiety containing 1, 2, 3, 4, 5 or 6 carbon atoms.
- species may include methyl, ethyl, 1-propyl (n-propyl), 2-propyl (iso-propyl, —CH(CH3)2), 1-butyl (n-butyl), 2- methyl-1-propyl (iso-butyl, —CH 2 CH(CH 3 ) 2 ), 2-butyl (sec-butyl, —CH(CH 3 )CH 2 CH 3 ), 2-methyl-2-propyl (t-butyl, —C(CH3)3), amyl, isoamyl, sec-amyl and other linear, cyclic and branch chain alkyl moieties.
- alkyl groups can contain species and groups described below for cycloalkyl, alkenyl, alkynyl groups, aryl groups, arylalkyl groups, alkylaryl groups and the like.
- Cycloalkyl as used herein is a monocyclic, bicyclic or tricyclic ring system composed of only carbon atoms.
- the term “cycloalkyl” encompasses a monocyclic or polycyclic aliphatic, non-aromatic radical, wherein each of the atoms forming the ring (i.e. skeletal atoms) is a carbon atom.
- the number of carbon atoms in an cycloalkyl substituent, moiety or group can vary and typically is 3 to about 50, e.g., about 1-30 or about 1-20, unless otherwise specified, e.g., C 3-8 alkyl or C3-C8 alkyl means an cycloalkyl substituent, moiety or group containing 3, 4, 5, 6, 7 or 8 carbon atoms and C 3-6 alkyl or C3-C6 means an cycloalkyl substituent, moiety or group containing 3, 4, 5 or 6 carbon atoms.
- Cycloalkyl substituents, moieties or groups will typically have 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 carbon atoms and may contain exo or endo- cyclic double bonds or endo-cyclic triple bonds or a combination of both wherein the endo-cyclic double or triple bonds, or the combination of both, do not form a cyclic conjugated system of 4n+2 electrons; wherein the bicyclic ring system may share one (i.e., spiro ring system) or two carbon atoms and the tricyclic ring system may share a total of 2, 3 or 4 carbon atoms, typically 2 or 3.
- cycloalkyl substituents, moieties or groups can contain moieties and groups described for alkenyl, alkynyl, aryl, arylalkyl, alkylaryl and the like and can contain one or more other cycloalkyl moieties.
- cycloalkyls may be saturated, or partially unsaturated.
- Cycloalkyls may be fused with an aromatic ring, and the points of attachment to the aromatic ring are at a carbon or carbons of the cycloalkyl substituent, moiety or group that is not an aromatic ring carbon atom.
- Cycloalkyl groups include groups having from 3 to 10 ring atoms.
- Cycloalkyl substituents, moieties or groups include cyclopropyl, cyclopentyl, cyclohexyl, adamantly or other cyclic all carbon containing moieties. Cycloalkyls further include cyclobutyl, cyclopentenyl, cyclohexenyl, cycloheptyl and cyclooctyl. Cycloalkyl groups may be substituted or unsubstituted.
- a cycloalkyl substituent can be a monoradical or a diradical (i.e., an cycloalkylene, such as, but not limited to, cyclopropan-1,1-diyl, cyclobutan-1,1-diyl, cyclopentan-1,1-diyl, cyclohexan-1,1-diyl, cyclohexan-1,4-diyl, cycloheptan-1,1-diyl, and the like).
- an cycloalkylene such as, but not limited to, cyclopropan-1,1-diyl, cyclobutan-1,1-diyl, cyclopentan-1,1-diyl, cyclohexan-1,1-diyl, cyclohexan-1,4-diyl, cycloheptan-1,1-diyl, and the like).
- Alkenyl or “alkene” as used herein means a substituent, moiety or group that comprises one or more double bond moities (e.g., —CH ⁇ CH—) or 1, 2, 3, 4, 5 or 6 or more, typically 1, 2 or 3 such moieties and can include an aryl moiety or group such as benzene, and additionally comprises linked normal, secondary, tertiary or cyclic carbon atoms, i.e., linear, branched, cyclic or any combination thereof unless the alkenyl moiety is a vinyl moiety (e.g., —CH ⁇ CH2).
- An alkenyl moiety, group or substituent with multiple double bonds may have the double bonds arranged contiguously (i.e.
- a 1, 3 butadienyl moiety or non-contiguously with one or more intervening saturated carbon atoms or a combination thereof, provided that a cyclic, contiguous arrangement of double bonds do not form a cyclically conjugated system of 4n+2 electrons (i.e., aromatic).
- the number of carbon atoms in an alkenyl group or moiety can vary and typically is 2 to about 50, e.g., about 2-30 or about 2-20, unless otherwise specified, e.g., C2-8 alkenyl or C2-8 alkenyl means an alkenyl moiety containing 2, 3, 4, 5, 6, 7 or 8 carbon atoms and C 2-6 alkenyl or C 2 -6 alkenyl means an alkenyl moiety containing 2, 3, 4, 5 or 6 carbon atoms.
- Alkenyl moieties or groups will typically have 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 carbon atoms.
- species include, by way of example and not limitation, any of the alkyl or cycloalkyl, groups moieties or substituents described herein that has one or more double bonds, methylene methylmethylene ( ⁇ CH—CH3), ethylmethylene ( ⁇ CH—CH2—CH3), ⁇ CH—CH2—CH2—CH3, vinyl (—CH ⁇ CH2), allyl, 1-methylvinyl, butenyl, iso-butenyl, 3-methyl-2-butenyl, 1-pentenyl, cyclopentenyl, 1-methyl-cyclopentenyl, 1-hexenyl, 3-hexenyl, cyclohexenyl and other linear, cyclic and branched chained all carbon containing moieties containing at least one double bond.
- alkenyl When alkenyl is used as a Markush group (i.e., a substituent) the alkenyl is attached to a Markush formula with which it is associated through an unsaturated carbon of a double bond of the alkenyl moiety or group unless specified otherwise.
- Alkynyl or “alkyne” as used herein means a substituent, moiety or group that comprises one or more triple bond moieties (i.e., —C ⁇ C—), e.g., 1, 2, 3, 4, 5, 6 or more, typically 1 or 2 triple bonds, optionally comprising 1, 2, 3, 4, 5, 6 or more double bonds, with the remaining bonds (if present) being single bonds and comprising linked normal, secondary, tertiary or cyclic carbon atoms, i.e., linear, branched, cyclic or any combination thereof, unless the alkynyl moiety is ethynyl.
- triple bond moieties i.e., —C ⁇ C—
- 1, 2, 3, 4, 5, 6 or more typically 1 or 2 triple bonds, optionally comprising 1, 2, 3, 4, 5, 6 or more double bonds, with the remaining bonds (if present) being single bonds and comprising linked normal, secondary, tertiary or cyclic carbon atoms, i.e., linear, branched,
- the number of carbon atoms in an alkenyl moiety or group can vary and typically is 2 to about 50, e.g., about 2-30 or about 2-20, unless otherwise specified, e.g., C 2-8 alkynyl or C 2 -8 alkynyl means an alkynyl moiety containing 2, 3, 4, 5, 6, 7 or 8 carbon atoms.
- Alkynyl groups will typically have 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 carbon atoms.
- species include, by way of example and not limitation, any of the alkyl moieties, groups or substituents described herein that has one or more double bonds, ethynyl, propynyl, butynyl, iso-butynyl, 3-methyl-2-butynyl, 1-pentynyl, cyclopentynyl, 1-methyl-cyclopentynyl, 1-hexynyl, 3-hexynyl, cyclohexynyl and other linear, cyclic and branched chained all carbon containing moieties containing at least one triple bond.
- alkynyl When an alkynyl is used as a Markush group (i.e., a substituent) the alkynyl is attached to a Markush formula with which it is associated through one of the unsaturated carbons of the alkynyl functional group.
- Aryl as used here means an aromatic ring system or a fused ring system with no ring heteroatoms comprising 1, 2, 3 or 4 to 6 rings, typically 1 to 3 rings, wherein the rings are composed of only carbon atoms; and refers to a cyclically conjugated system of 4n+2 electrons (Huckel rule), typically 6, 10 or 14 electrons some of which may additionally participate in exocyclic conjugation (cross-conjugated (e.g., quinone).
- Aryl substituents, moieties or groups are typically formed by five, six, seven, eight, nine, or more than nine, carbon atoms.
- Aryl substituents, moieties or groups are optionally substituted.
- Exemplary aryls include C 6 -C 10 aryls such as phenyl and naphthalenyl and phenanthryl.
- an aryl group can be a monoradical or a diradical (i.e., an arylene group).
- Exemplary arylenes include, but are not limited to, phenyl-1,2-ene, phenyl-1,3-ene, and phenyl-1,4-ene.
- aryl When aryl is used as a Markush group (i.e., a substituent) the aryl is attached to a Markush formula with which it is associated through aromatic carbon of the aryl group.
- Arylalkyl as used herein means a substituent, moiety or group where an aryl moiety is bonded to an alkyl moiety, i.e., -alkyl-aryl, where alkyl and aryl groups are as described above, e.g., —CH2—C6H5 or —CH2CH(CH3)—C6H5.
- alkyl When arylalkyl is used as a Markush group (i.e., a substituent) the alkyl moiety of the arylalkyl is attached to a Markush formula with which it is associated through a sp 3 carbon of the alkyl moiety.
- Alkylaryl as used herein means substituent, moiety or group where alkyl moiety is bonded to aryl moiety, i.e.,-aryl-alkyl, where aryl and alkyl groups are as described above, e.g. —C 6 H 4 —CH 3 or —C 6 H 4 —CH 2 CH(CH 3 ).
- alkylaryl When alkylaryl is used as Markush group (i.e., substituent), aryl moiety of alkylaryl is attached to Markush formula with which it is associated through sp 2 carbon of the aryl moiety.
- “Substituted alkyl”, “substituted cycloalkyl”, “substituted alkenyl”, “substituted alkynyl”, substituted alkylaryl”, “substituted arylalkyl”, “substituted heterocycle”, “substituted aryl” and the like as used herein mean alkyl, alkenyl, alkynyl, alkylaryl, arylalkyl heterocycle, aryl or other group or moiety as defined or disclosed herein that has substituent(s) that replaces hydrogen atom(s) or substituent(s) that interrupts carbon atom chain.
- Heterocycle or “heterocyclic” or “heteroaryl” as used herein means a cycloalkyl or aromatic ring system wherein one or more, typically 1, 2 or 3, but not all of the carbon atoms comprising the ring system are replaced by a heteroatom which is an atom other than carbon, including, N, O, S, Se, B, Si, P, typically N, O or S wherein two or more heteroatoms may be adjacent to each other or separated by one or more carbon atoms, typically 1-17 carbon atoms, 1-7 atoms or 1-3 atoms.
- Heterocycles includes heteroaromatic rings (also known as heteroaryls) and heterocycloalkyl rings (also known as heteroalicyclic groups) containing one to four heteroatoms in the ring(s), where each heteroatom in the ring(s) is selected from O, S and N, wherein each heterocyclic group has from 4 to 10 atoms in its ring system, and with the proviso that the any ring does not contain two adjacent O or S atoms.
- Non-aromatic heterocyclic, substituents, moieties or groups also known as heterocycloalkyls
- aromatic heterocyclic groups have at least 5 atoms in their ring system and include benzo-fused ring systems.
- Heterocyclics with 3, 4, 5, 6 and 10 atoms include aziridinyl azetidinyl, thiazolyl, pyridyl and quinolinyl, respectively.
- Nonaromatic heterocyclic substituents, moieties/groups are pyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothienyl, oxazolidinonyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl, thiomorpholinyl, thioxanyl, piperazinyl, aziridinyl, azetidinyl, oxetanyl, thietanyl, homopiperidinyl, oxepanyl, thiepanyl, oxazepinyl, diazepinyl, thiazepiny
- Aromatic heterocyclic includes, by way of example and not limitation, pyridinyl, imidazolyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl, tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxazolyl, isothiazolyl, pyrrolyl, quinolinyl, isoquinolinyl, indolyl, benzimidazolyl, benzofuranyl, cinnolinyl, indazolyl, indolizinyl, phthalazinyl, pyridazinyl, triazinyl, isoindolyl, pteridinyl, purinyl, oxadiazolyl, thiadiazolyl, furazanyl, benzofurazanyl, benzo-thiophenyl, benzothiazolyl, benzoxazolyl, qui
- Non-aromatic heterocycles may be substituted with one or two oxo ( ⁇ O) moieties and includes pyrrolidin-2-one.
- “Heteroaryl” as used herein means an aryl ring system wherein one or more, typically 1, 2 or 3, but not all of the carbon atoms comprising the aryl ring system are replaced by a heteroatom which is an atom other than carbon, including, N, O, S, Se, B, Si, P, typically, oxygen (—O—), nitrogen (—NX—) or sulfur (—S—) where X is —H, protecting group or C 1-6 optionally substituted alkyl, wherein heteroatom participates in conjugated system either through pi-bonding with adjacent atom in ring system or through lone pair of electrons on heteroatom and may be optionally substituted on one or more carbons or heteroatoms, or combination of both, in manner which retains cyclically conjugated system.
- heteroaryls include by way of example and not limitation pyridyl, thiazolyl, pyrimidinyl, furanyl, thienyl, pyrrolyl, pyrazolyl, purinyl, imidazolyl, benzofuranyl, indolyl, isoindoyl, quinolinyl, isoquinolinyl, benzimidazolyl, pyridazinyl, pyrazinyl, benzothiopyran, benzotriazine, isoxazolyl, pyrazolopyrimidinyl, quinoxalinyl, thiadiazolyl, and triazolyl.
- Heterocycles that are not heteroaryls include, by way of example and not limited to, tetrahydrothiophenyl, tetrahydrofuranyl, indolenyl, piperidinyl, pyrrolidinyl, 2-pyrrolidonyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, octahydroisoquinolinyl, 2H-pyrrolyl, 3H-indolyl, 4H-quinolizinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, piperazinyl, quinuclidinyl, morpholinyl and oxazolidinyl.
- Monocyclic heteroaryls include, by way of example and not limitation, pyridinyl, imidazolyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl, tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxazolyl, isothiazolyl, pyrrolyl, pyridazinyl, triazinyl, oxadiazolyl, thiadiazolyl, and furazanyl.
- Heteroaryls include those substituents, moieties or groups containing 0-3 N atoms, 1-3 N atoms or 0-3 N atoms, 0-1 O atoms and 0-1 S atoms.
- a heteroaryl may be monocyclic or bicyclic.
- the ring system of a heteroaryls ring typically contains 1-9 carbons (i.e., C1-C9 heteroaryl).
- Monocyclic heteroaryls include C 1 -C 5 heteroaryls.
- Monocyclic heteroaryls include those having 5-membered or 6- membered ring systems.
- Bicyclic heteroaryls include C6-C9 heteroaryls.
- a heteroaryl group can be a monoradical or a diradical (i.e., a heteroarylene group).
- “Ether” as used herein in the terms “aryl ether, alkyl ether, aryl alkyl ether, alkoxy alkyl ether, alkyne alkyl ether, and alkylene alkyl ether” mean an organic moiety, group or substituent that comprises or consists of 1, 2, 3, 4 or more —O— moieties, usually 1 or 2, wherein no two —O— moieties are immediately adjacent (i.e., directly attached) to each other.
- ethers comprise an organic moiety containing 1-50 carbon atoms, 1-20 carbon atoms or 1-8 carbon atoms and 0 to 10 independently selected heteroatoms (e.g., O, S, N, P, Si), typically 0-2.
- An ether moiety, group or substituent includes organic moiety-O— wherein the organic moiety is as described herein for alkyl or optionally substituted alkyl group.
- ether is used as a Markush group (i.e., a substituent) the oxygen of the ether functional group is attached to a Markush formula with which it is associated.
- ether is a used as substituent in a Markush group it is sometimes designated as an “alkoxy” group.
- Alkoxy includes C1-C4 ether substituents such as, by way of example and not limited to, methoxy, ethoxy, propoxy, iso-propoxy and butoxy. Ether further includes those substituents, moieties or groups that contain one (excluding ketal) or more —OCH2CH2O—, moieties in sequence (polyethylene or PEG moieties).
- Halogen or “halo” as used herein means fluorine, chlorine, bromine or iodine.
- Hydroxroxyl as used herein means –OH, and the “alkylhydroxyl” means —OH is attached to alkyl groupl; wherein alkyl group is as defined above.
- Haloalkyl as used herein means an alkyl substituent moiety or group in which one or more of its hydrogen atoms are replaced by one or more independently selected halide atoms.
- Haloalkyl includes C1-C4 haloalkyl.
- Example but non-limiting C1-C4 haloalkyls are —CH2Cl, CH2Br, —CH2I, —CHBrCl, —CHCl—CH2Cl and —CHCl—CH2I.
- Haloalkylene as used herein means an alkylene substituent, moiety or group in which one or more hydrogen atoms are replaced by one or more halide atoms.
- Haloalkylene includes C1-C6 haloalkylenes or C1-C4 haloalkylenes.
- Fluoroalkyl as used herein means an alkyl in which one or more hydrogen atoms are replaced by a fluorine atom. Fluoroalkyl includes C 1 -C 6 and C 1 -C 4 fluoroalkyls. Example but non-limiting fluoroalkyls include —CH3F, —CH2F2 and —CF3 and perfluroalkyls.
- “Fluoroalkylene” as used herein means an alkylene in which one or more hydrogen atoms are replaced by a fluorine atom.
- Fluoroalkylene includes C 1 -C 6 fluoroalkylenes or C 1 -C 4 fluoroalkylenes.
- the term “heteroalkyl” refers to an alkyl group in which one or more skeletal atoms of the alkyl are selected from an atom other than carbon, e.g., oxygen, nitrogen, sulfur, phosphorus or combinations thereof.
- a heteroalkyl is a C1-C6 heteroalkyl.
- alkylene employed alone or in combination with other terms, refers to a divalent alkyl linking group.
- alkylene groups include, but are not limited to, ethan-1,2-diyl, propan-1,3-diyl, propan-1,2-diyl, butan-1,4-diyl, butan-1,3- diyl, butan-1,2-diyl, 2-methyl-propan-1,3-diyl, and the like.
- alkoxy employed alone or in combination with other terms, refers to a group of formula —O-alkyl, wherein the alkyl group as defined above.
- Example alkoxy groups include but not limited to methoxy, ethoxy, propoxy (e.g., n- propoxy and isopropoxy), t-butoxy, and the like.
- alkylalkoxy refers to a group of formula —alkyl- O-alkyl, wherein the alkyl group is as defined above.
- alkylamino refers to a group of formula —NH(alkyl), wherein the alkyl group is as defined above.
- arylamino refers to a group of formula —NH(aryl), wherein the aryl or aromatic group is as defined above.
- alkoxycarbonyl refers to a group of formula —C(O)O-alkyl, wherein the alkyl group is as defined above.
- alkylcarbonylamino refers to a group of formula — NHC(O)-alkyl, wherein the alkyl group is as defined above.
- alkylsulfonylamino refers to a group of formula —NHS(O)2- alkyl, wherein the alkyl group is as defined above.
- aminonosulfonyl refers to a group of formula —S(O) 2 NH 2 .
- alkylaminosulfonyl refers to a group of formula — S(O)2NH(alkyl), wherein the alkyl group is as defined above.
- aminocarbonyl employed alone or in combination with other terms, refers to a group of formula —NHC(O)-.
- alkylaminocarbonyl employed alone or in combination with other terms, refers to a group of formula —alkyl-NHC(O)- or —NHC(O)-alkyl-.
- alkylacylamino employed alone or in combination with other terms, refers to a group of formula —alkyl-C(O)-alkyl/aryl/heteroparyl-NH2.
- aminocarbonylamino refers to a group of formula —NHC(O)NH 2 .
- sulfanyl or “thio” refers to a group of formula —SH.
- alkylthio or “alkylsulfanyl” refers to a group of formula —S-alkyl, wherein the alkyl group is as defined above.
- arylthio or “arylsulfanyl” refers to a group of formula —S-aryl, wherein the aryl group is as defined above.
- heteroarylthio or “heteroarylsulfanyl” refers to a group of formula —S-heteroaryl, wherein the heteroaryl group is as defined above.
- sulfonyl refers to a group of formula —S(O) 2 -.
- alkylsulfonyl refers to a group of formula —S(O)2-alkyl, wherein the alkyl group is as defined above.
- arylsulfonyl refers to a group of formula —S(O) 2 -aryl, wherein the aryl group is as defined above.
- heteroarylsulfonyl refers to a group of formula —S(O)2-heteroaryl, wherein the heteroaryl group is as defined above.
- sulfonyloxy refers to a group of formula —S(O) 2 -O-.
- alkylsulfonyloxy refers to a group of formula —S(O) 2 -O-alkyl, wherein the alkyl group is as defined above.
- sulfinyl refers to a group of formula —S(O)-.
- alkylsulfinyl refers to a group of formula —S(O)-alkyl, wherein the alkyl group is as defined above.
- arylsulfinyl refers to a group of formula —S(O)-aryl, wherein the aryl group is as defined above.
- amino refers to a group of formula —NH 2 .
- carbamyl to a group of formula —C(O)NH2.
- carbonyl employed alone or in combination with other terms, refers to a —C(O)— group.
- alkylcarboxy refers to a group of formula —C(O)OH connected with at least one of alkyl group.
- dialkylamino refers to a group of formula —N(alkyl)2, wherein the two alkyl groups each is as defined above.
- alkyl cycloalkyl refers to a group of formula —alkyl attached to cycloalkyl group, wherein the alkyl and cycloalkyl groups each are as defined above.
- haloalkoxy refers to a group of formula —O-haloalkyl where alkyl and halo/halogen is as defined above.
- haloalkoxy group is OCF3.
- the haloalkoxy group is fluorinated only.
- haloalkyl employed alone or in combination with other terms, refers to an alkyl group having from one halogen atom to 2 s+1 halogen atoms which may be the same or different, where “s” is the number of carbon atoms in the alkyl group, wherein the alkyl and halo is as defined above.
- haloaryl refers to a group of formula — halo-aryl where aryl and halo/halogen is as defined above.
- the compounds described herein can be asymmetric (e.g., having one or more stereocenters).
- the compound has the (R)-configuration. In some embodiment, compound has (S)-configuration.
- compound used herein is meant to include all stereoisomers, geometric iosomers, tautomers, and isotopes of structures depicted. Compounds herein identified by name or structure as one particular tautomeric form are intended to include other tautomeric forms unless otherwise specified. All compounds, and pharmaceutically acceptable salts thereof, can be found together with other substances such as water and solvents (e.g. hydrates and solvates) or can be isolated.
- ambient temperature and “room temperature” or “rt” as used herein, are understood in the art, and refer generally to a temperature, e.g.
- reaction temperature that is about the temperature of the room in which the reaction is carried out, for example, a temperature from about 20° C. to about 30° C.
- the present invention provides a manganese based catalyst complex of Formula I, for hydrogenation of substrate wherein the substrate is select from ⁇ , ⁇ - unsaturated ketone, aldehyde and imine (of Formula IIA or IIB); the formula I is represented by: Formula I wherein, Mn is manganese atom or manganese ion in oxidation state (I); moieties attached to said Mn are selected from heteroaryl rings, one or more carbon monoxide groups, -PR 3 R 4 -NR 2 and X, wherein said nitrogen of -PR 3 R 4 -NR 2 is further attached to said one of heteroaryl rings, and wherein said heteroaryl rings are selected from pyridine and diazole; wherein R 1 is selected from the group consisting of hydrogen, (C1-C4)alkyl, aryl, alkyl aryl, alkoxy, cycloalkyl, alkyl cycloalkyl, and alkylcarboxy; R 2 is selected from the group consisting of hydrogen
- the Mn complex of formula I is defined by R1 being hydrogen, R2 being hydrogen or C1-C4alkyl, R3 being C1-C4alkyl or aryl, R4 being C1-C4alkyl or aryl, and X being halogen.
- Said Mn based catalyst comprises a mixed-donor ligand with different electronic features of donating center which suitably administer the electronic requirement at the metal center (Mn) and stabilize the active catalytic species.
- Mn metal center
- the presence of NH on the side-arm could facilitate the non-innocent behavior of ligand via aromatization/dearomatization approach leading to the heterolytic activation of molecules.
- the present disclosure provides a process of preparation of a novel manganese catalyst (Formula I) under mild conditions which comprising reacting compound of formula III and substituted pentacarbonylmanganese [Mn(CO) 5 X] at room temperature to yield a novel manganese catalyst (Formula I) Formula III wherein R 1 , R 2 , R 3 , R 4 and X are same as defined above under formula I.
- the present disclosure provides a process of preparation of novel manganese catalyst of Formula I, the steps comprising: a) reacting 0.16-0.24 mmol of compound of formula III with 0.16-0.24 mmol of substituted pentacarbonylmanganese [Mn(CO) 5 X] in a container such as round bottom flask with a solvent to obtain a reaction mixture Formula III wherein R 1 , R 2 , R 3 , R 4 and X are same as defined above under formula I; b) stirring the reaction mixture under inert atmosphere at temperature in the range of 27- 80 o C for a time period of up to 48 hrs; c) purifying the mixture to obtain the manganese catalyst of Formula I.
- the compound of formula III used in step a) is selected from N- (di-tert-butylphosphaneyl)-6-(1H-pyrazol-1-yl)pyridin-2-amine (L3), N-(di-n- propylphosphaneyl)-6-(1H-pyrazol-1-yl)pyridin-2-amine (L2), N- (diphenylphosphaneyl)-6-(1H-pyrazol-1-yl)pyridin-2-amine (L1), and N-(di-tert- butylphosphaneyl)-N-methyl-6-(1H-pyrazol-1-yl)pyridin-2-amine (L4).
- the solvent used in step a) is selected from THF (tetrahydrofuran), 2-methyl THF, and toluene.
- the amount of compound of formula III used in the reaction is inert atmosphere in step a) is attained by argon or helium.
- the amount of compound of formula III used in the reaction is 0.16 mmol, 0.20 mmol or 0.24 mmol.
- amount of compound of formula III and substituted pentacarbonylmanganese used in reaction is 0.16 mmol, 0.20 mmol or 0.24 mmol respectively.
- the novel manganese catalyst (Formula I) for hydrogenation of ⁇ , ⁇ -unsaturated ketones, aldehydes and imines is selected from group consisting of: 1. N-(diphenylphosphaneyl)-6-(1H-pyrazol-1-yl)pyridin-2-amine-Mn(CO) 2 Br complex(1a) (Mn-1) 2. N-(di-iso-propylphosphaneyl)-6-(1H-pyrazol-1-yl)pyridin-2-amine-Mn(CO)2Br complex (1b) (Mn-2) 3.
- Mn-1 to Mn-3 and 1d it displayed three IR peaks for carbonyls ranging between 1857-2053 cm -1 .
- ⁇ , ⁇ -unsaturated ketones, aldehyde, ketone or imine is hydrogenated to yield hydrogenated product (Formula IV), Formula IV wherein X is oxo group (O) or or nitrogen (NR 1 ) group, where R 1 is alkyl or aryl moiety; R is hydrogen, alkyl (C1-C10), (un)substituted aryl, (un)substituted heteroaryl, alkene, alkyne; A and Y is independently selected from hydrogen, alkyl (C1-C10), (un)substituted aryl, (un)substituted heteroaryl, alkene, alkyne, ferrocene, alkoxy, where the substituted aryl or heteroaryl maybe further substituted with aryl, alkoxy, alkyl, halogen, nitro, cyano, aryl ether, alkyl ether, aryl alkyl
- the hydrogenated products catalyzed by the novel manganese catalyst (Formula I) of ⁇ , ⁇ -unsaturated ketones, aldehydes, and imines (of Formula IIA or IIB) is selected from group consisting of: (i) 1-(3-(Allyloxy)phenyl)-3-phenylpropan-1-one (2a) (ii) 3-Phenyl-1-(3-(prop-2-yn-1-yloxy)phenyl)propan-1-one (2b) (iii) 1-(3-(Oxiran-2-ylmethoxy)phenyl)-3-phenylpropan-1-one (2c) (iv) 2-(4-Acetylphenoxy)-1,3-diphenylpropan-1-one (2d)
- the present disclosure provides a process for hydrogenation of various substrates such as ⁇ , ⁇ -unsaturated ketones, aldehydes, and imines (of Formula IIA or IIB) by using a novel
- the base is selected from the group consisting of potassium carbonate, potassium phosphate, potassium hydroxide, potassium tert-butoxide, sodium tert-butoxide, sodium carbonate, cesium carbonate, sodium hydroxide, lithium carbonate, lithium hydroxide, calcium hydroxide, potassium bicarbonate, sodium bicarbonate, sodium methoxide, lithium bicarbonate and tertiary amines, most preferably base used in the present invention is Tripotassium phosphate.
- Solvents used in the present invention include simple alcohols, such as C1-10 hydrocarbyl alcohols, often saturated aliphatic C1-8alcohols, for example, ethanol, isopropanol and tert-butanol; polyvalent alcohols such as ethylene glycol, propylene glycol, 1,2-propanediol and glycerol; ethers, for example tetrahydrofuran (THF) 1,4- dioxane, methyl tert-butyl ether, cyclopentyl methyl ether; aliphatic and aromatic hydrocarbon solvents, for example C5-12alkanes, benzene, toluene and xylene and halogenated (typically chlorinated) hydrocarbon solvents, for example dichloromethane and chlorobenzene, or mixtures thereof, in particular, mixtures of alcohols, for example ethanol or isopropanol, and hydrocarbon solvents such as hexanes, xylene
- reaction at step i) is in the range of 20 °C-40 °C.
- reaction at step i) is conducted at 27°C and the duration of hydrogenation reaction is quite low, preferably time requires is 1 hour to 5 hours.
- the methods of the invention, as is typical for hydrogenation reactions, are conducted in the presence of hydrogen gas, under pressure.
- the pressure at which the reactions are conducted is in the range of about 1 bar (100 kPa) to about 100 bar (10,000 kPa), for example from about 20 bar (2,000 kPa) to about 80 bar (8,000 kPa), although higher or lower pressures may on occasion be convenient, pressure at which hydrogenation reaction of the present invention is carried out is much lower, 5 bar.
- catalyzing the hydrogenation of various substrates especially ketones require low catalyst loading.
- compound comprising a charged or neutral complex of formula (I), wherein —N is substituted one or more times with the second electron donating group and at least one of R 1 and R 2 are substituted one or more times with the first electron donating group.
- form of Mn-catalyst and compound of Formula (I) is amorphous.
- ligands are tridentate attached to Mn complex represents tridentate neutral or anionic ligand.
- the Mn catalysts disclosed the t Bu-substituted complex Mn(CO)2Br shows an exceptional chemoselective catalytic reduction of unsaturated bonds in a wide range of ⁇ , ⁇ -unsaturated ketones/aldehydes/imines.
- This hydrogenation tolerates a range of highly sensitive functionalities, such as halides (-F, -Cl, -Br, -I), alkoxy, hydroxy and epoxide, including hydrogen sensitive moieties like acetyl, nitrile, nitro, unconjugated alkenyl and alkynyl groups.
- the employment of a mild base, moderate H2 pressure and room temperature (27 o C) in the Mn-catalyzed hydrogenation are highly advantageous to the commonly employed KO t Bu base and extreme reaction conditions.
- the ( tBu2 PNN Pyz )Mn(I) catalyst could hydrogenate diverse unsaturated ketones to saturated ketones at room temperature with the compatibility of sensitive functionalities, such as halides ( ⁇ F, ⁇ Cl, ⁇ Br, ⁇ I), alkoxy, hydroxy, epoxide, acetyl, nitrile, nitro, unconjugated alkenyl and alkynyl groups.
- sensitive functionalities such as halides ( ⁇ F, ⁇ Cl, ⁇ Br, ⁇ I)
- alkoxy hydroxy
- epoxide acetyl
- nitrile nitro
- unconjugated alkenyl and alkynyl groups unconjugated alkenyl and alkynyl groups.
- ligand precursor 6-(1H-pyrazol-1-yl)pyridin-2-amine, ligands L1 and L3 were prepared according to the previously described procedures (refer, D. Gong et al., J. Mol. Catal. A Chem., 2014, 395, 100-107; H. Chen et al., Polym. Chem., 2017, 8, 1805-1814; and D.
- Example 1 Synthesis of N-(di-iso-propylphosphaneyl)-6-(1H-pyrazol-1-yl)pyridin- 2-amine (L2): In 50 mL oven dried Schlenk flask, 6-(1H-pyrazol-1-yl)pyridin-2-amine (0.20 g, 1.25 mmol) was dissolved in THF (10 mL) followed by addition of freshly distilled Et3N (0.21 S4 mL, 1.5 mmol) under inert atmosphere.
- reaction mixture was cooled to 0oC and chlorodiisopropylphosphine (0.21 g, 1.37 mmol) was added dropwise. The reaction mixture was allowed to room temperature and stirred for 1 h. Further reaction mixture was cooled to -78oC and n-BuLi (0.94 mL, 1.5 mmol; 1.6 M in THF) was added dropwise resulting in colorless solution. Then reaction was allowed to room temperature and stirred for 1 h, followed by heating at 60 oC for 16 h. Volatiles were evaporated under vacuum and 30 mL of toluene was added into it.
- Example 2 N-(Di-tert-butylphosphaneyl)-N-methyl-6-(1H-pyrazol-1-yl)pyridin-2- amine (L4): In 50 mL round bottom flask, N-(di-tert-butylphosphaneyl)-6-(1H-pyrazol- 1- yl)pyridin-2-amine (0.10 g, 0.33 mmol) in THF (5 mL) was cooled to -20 oC and n- BuLi (0.25 mL, 0.40 mmol; 1.6 M in hexane) was added followed by the addition of MeI (0.055 g, 0.39 mmol).
- Example 4 Synthesis and characterization of Mn-catalyst (1c)(Mn-2): This catalyst was synthesized following the procedure similar to the synthesis of Mn-1 (example 1), using N-(di-iso-propylphosphaneyl)-6-(1Hpyrazol-1-yl)pyridin-2-amine (L2; 0.060 g, 0.217 mmol) and Mn(CO)5Br (0.060 g, 0.218 mmol). The complex Mn-2 was obtained as an orange powder. Yield: 0.090 g (89%).
- Example 5 Synthesis and characterization of Mn-catalyst (1c) (Mn-3)
- N-(di-tert-butylphosphaneyl)-6-(1H-pyrazol-1-yl)pyridin- 2-amine L3, 0.050 g, 0.16 mmol
- Mn(CO)5Br 0.45 g, 0.16 mmol
- THF 3 mL
- Reaction mixture was stirred under inert atmosphere at room temperature (27 o C) for 48 h. By the time the color of reaction mixture was changed from yellow to red.
- the reaction mixture was concentrated to 0.5 mL.
- Example 6 Synthesis and characterization of Mn-catalyst (1d) (Mn-4): This complex was synthesized following the procedure similar to the synthesis of Mn-1, using N-(di-tert-butylphosphaneyl)-N-methyl-6- (1H-pyrazol-1-yl)pyridin-2-amine (L4, 0.042 g, 0.132 mmol) and Mn(CO)5Br (0.036 g, 0.131 mmol), and the reaction mixture was stirred at room temperature (27 oC) for 16 h. The complex Mn-3Me was obtained as an orange powder. Yield: 0.060 g (85%).
- Example 7 General procedure for hydrogenation of substrates.
- a substrate such as ⁇ , ⁇ -unsaturated ketones or aldehydes or imines (of Formula IIA or IIB) in presence of Mn-catalyst (Formula I) (5mol%), base (10 mol%) was reacted in dry vial with stir bar, inside the glove box. Reaction vial was transferred to autoclave under argon atmosphere. Polar solvent was added and pressurized autoclave with H2 (5 bar) and vented for five times. The autoclave was pressurized with 5 bar H 2 and stirred (700 rpm) at 27 o C for 1 h.
- reaction mixture was concentrated and subjected to column chromatography on silica gel where petroleum ether & ethyl acetate was used in ratio of 70:1, after separation and purification, yielded desired hydrogenated products.
- Table 1 Optimization of Reaction Parameters
- Example 8 Synthesis of 1,3-diphenylpropan-1-one: To a dry vial with stir bar was introduced catalyst I (0.005 g, 0.01 mmol), K3PO4 (0.0043 g, 0.02 mmol), and (E)-chalcone (0.042 g, 0.202 mmol) inside the glove box.
- reaction vial was transferred to an autoclave under argon atmosphere. Then MeOH (1.0 mL) was added and the autoclave was pressurized with H2 (5 bar) and vented for five times. Finally, the autoclave was pressurized with 5 bar H 2 and stirred (700 rpm) at room temperature (27 o C) for 1 h. After reaction time, the reaction mixture was concentrated and subjected to column chromatography on silica gel (petroleum ether/EtOAc: 70/1) to yield 1,3-diphenylpropan-1-one (0.041 g, 97%) as white solid.
- Example 9 Synthesis of 1-(3-(Allyloxy)phenyl)-3-phenylpropan-1-one (2a) (15): The representative procedure was followed, using substrate (E)-1-(3-(allyloxy)phenyl)-3- phenylprop-2-en-1-one (0.053 g, 0.201 mmol) and the reaction mixture was stirred at room temperature (27 oC) for 3 h.
- Example 10 Synthesis of 3-Phenyl-1-(3-(prop-2-yn-1-yloxy)phenyl)propan-1-one (2b) (16): The representative procedure was followed, using substrate (E)-3-phenyl-1-(3-(prop-2- yn-1-yloxy)phenyl)prop-2-en-1-one (0.053 g, 0.202 mmol) and the reaction mixture was stirred at room temperature (27 o C) for 3 h.
- Example 11 Synthesis of 1-(3-(Oxiran-2-ylmethoxy)phenyl)-3-phenylpropan-1-one (2c) (17): The representative procedure was followed, using substrate (E)-1-(3-(oxiran-2- ylmethoxy)phenyl)-3-phenylprop-2-en-1-one (0.057 g, 0.203 mmol) and the reaction mixture was stirred at room temperature (27 oC) for 4 h.
- Example 12 Synthesis of 2-(4-Acetylphenoxy)-1,3-diphenylpropan-1-one (2d) (40): The representative procedure was followed, using substrate (Z)-2-(4-acetylphenoxy)-1,3- diphenylprop-2-en-1-one (0.069 g, 0.202 mmol) and the reaction mixture was stirred at room temperature (27 oC) for 3 h. Purification by column chromatography on silica gel (petroleum ether/EtOAc: 30/1) yielded 2-(4-Acetylphenoxy)-1,3-diphenylpropan-1-one (0.040 g, 57%) as yellow solid.
- the present invention provides process of hydrogenation wherein the novel manganese catalyst used for hydrogenation of various substrates such as ⁇ , ⁇ - unsaturated ketones, aldehydes, and imines (of Formula IIA or IIB).
- Hydrogenation of various substrates such as ⁇ , ⁇ -unsaturated ketones , aldehydes, and imines (of Formula IIA or IIB) is carried out at room temperature and low H2 pressure, wherein lower temperature conditions are quite suitable to yield high purified and selectively hydrogenated products.
- the Mn catalyst of formula I Hydrogenation at pressure of 5 bar H2 and room temperature. ⁇ Use of mild base and atom-efficient H 2 source. ⁇ Provides broad substrates scope with excellent tolerance of hydrogen-sensitive functionalities. ⁇ Using the sustainable molecular hydrogen and a mild K3PO4 base, the Mn catalyst of formula I hydrogenate diverse unsaturated ketones at room temperature with the compatibility of sensitive functionalities, such as halides (- F, -Cl, -Br, -I), alkoxy, hydroxy, epoxide, acetyl, nitrile, nitro, unconjugated alkenyl and alkynyl groups.
- sensitive functionalities such as halides (- F, -Cl, -Br, -I), alkoxy, hydroxy, epoxide, acetyl, nitrile, nitro, unconjugated alkenyl and alkynyl groups.
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Abstract
The present invention provides a novel manganese catalyst (Formula I) and their process of preparation thereof. The present invention also provides process of hydrogenation wherein the novel manganese catalyst used for hydrogenation of various substrates such as α,β-unsaturated ketones, aldehydes, and imines (of Formula IIA or IIB).
Description
MANGANESE BASED CATALYST, ITS PROCESS OF PREPARATION AND THEIR USE IN PROCESS OF HYDROGENATION REACTIONS FIELD OF THE INVENTION The present invention provides a novel manganese based catalyst of Formula I, its process of preparation, and their use in a process of hydrogenation of different substrates. More particularly, the present invention provides a process of hydrogenation where the novel manganese catalyst of Formula I is used for hydrogenation of various substrates of Formula IIA or IIB such as α,β-unsaturated ketones, aldehydes, imines, etc. BACKGROUND AND PRIOR ART OF THE INVENTION In modern synthetic organic chemistry, chemo- and regioselective hydrogenation of α,β- unsaturated ketones, aldehydes and imines is always a challenging procedure. The catalytic reduction of polar multiple bonds via molecular hydrogen plays a significant role. Use of catalytic procedures in combination with hydrogen gas displays an attractive option to develop efficient and cleaner processes. In last few years, well-defined Mn(I) complexes were introduced as powerful players in field of sustainable hydrogenation chemistry, being active for hydrogenation of not only aldehydes, ketones, esters, CO2, and carbonates but also nitrogen-containing compounds such as imines, nitriles, amides, and heterocycles. Many of these transition-metal catalyzed hydrogenations rely on metal−ligand bifunctional catalysis (metal−ligand cooperation), where complexes contain electronically coupled hydride and acidic hydrogen atoms. An effective way of bond activation by metal−ligand cooperation involves aromatization/dearomatization of the ligand in pincer complexes in which a central pyridine-based backbone is connected with −CH2PR2 and/or −CH2NR2 substituents. This has resulted in the development of novel and unprecedented iron and manganese catalysis, where this type of cooperation plays a key role in the heterolytic cleavage of H2. An overview of well-defined manganese complexes for hydrogenation reactions is depicted by Stefan Weber et al in the journal “Organometallics 2021, 40, 1388−1394”. An alternative way to activate dihydrogen was recently described in this publication. This article also discloses about the Mn(I) alkyl carbonyl complexes which are known to undergo insertions to form highly reactive acyl intermediates which are able to activate
dihydrogen, thereby forming the 16e− Mn(I) hydride catalysts. Accordingly, bisphosphine manganese tricarbonyl complexes containing alkyl ligands could be employed for the additive-free hydrogenation of alkenes and nitriles. The reaction conditions are very harsh to achieve the hydrogenation of alkenes and nitriles. Manganese catalysts and their use in hydrogenation of ketones is disclosed in the US patent application number ‘US2022119329A1’ wherein hydrogenation of ketones involves higher pressure and temperature conditions. Chemo- and regioselective hydrogenation of alkenes and carbonyls under mild conditions is crucial to achieve sustainable synthesis. Most of the known catalysts for hydrogenation of various substrates such as α,β-unsaturated ketones, aldehydes and imines requires expensive catalysts and/or harsh reaction conditions (high H2 pressure and high reaction temperature). Therefore, there is a need to provide a chemo and regioselective hydrogenation catalyst useful for the hydrogenation of various substrates such as α,β-unsaturated ketones, aldehydes, imines, etc. OBJECTS OF THE INVENTION The main objective of the present invention is to provide a novel manganese catalyst of Formula I, for a catalytic hydrogenation processes. Another objective of the present invention is to provide a process of preparation of said manganese based catalyst of formula I. Yet another objective of the present invention is to provide a process for hydrogenation of various substrates such as α,β-unsaturated ketones, aldehydes and imines by using said manganese catalyst (of Formula I). BRIEF DESCRIPTION OF DRAWINGS Fig 1: The synthetic scheme explaining general process of hydrogenation of substrates such as α,β-unsaturated ketones, aldehydes and imines by using the manganese catalyst (of Formula I).
Fig 2: The synthetic scheme explaining process of preparation of the manganese based catalyst of formula I. Fig 3: ORTEP (Oak Ridge Thermal-Ellipsoid Plot Program) of compound Mn-2 showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. Selected bond length (Å): Br1 ^Mn1, 2.5916(7); Mn1 ^C9, 1.773(4); Mn1 ^C10, 1.797(4); Mn1 ^N3, 2.011(3); Mn1 ^N1, 2.012(3); Mn1 ^P1, 2.2462(12). Selected bond angles ( ^): N3 ^Mn1 ^P1, 160.49(11); C10 ^Mn1 ^N1, 175.88(16); C9 ^Mn1 ^Br1, 175.54(14); C9 ^Mn1 ^C10, 87.40(19); C9 ^Mn1 ^N1, 96.23(16); N1 ^Mn1 ^Br1, 84.57(9). Fig 4: Product Scope and Scheme of Mn-Catalyzed C=C Bond Hydrogenation of α,β– Unsaturated Ketones (aReaction Conditions: Substrate, α,β-unsaturated ketone (0.20 mmol), Mn-3 (0.005 g, 0.01 mmol, 5 mol%), K3PO4 (0.0043 g, 0.02 mmol), MeOH (1.0 mL), H2 (5 bar). Yields are of isolated compounds. b Reaction at 50 oC. c Mixture of MeOH : DCM (4 : 1) used. d Reaction at 10 bar H2 and 50 oC.). Fig 5: Product Scope and Scheme of Mn-Catalyzed Hydrogenation of Aldehydes and Imines (aReaction Conditions: Substrate (0.20 mmol), Mn-3 (0.005 g, 0.01 mmol, 5 mol%), K3PO4 (0.0043 g, 0.02 mmol), H2 (5 bar), MeOH (1.0 mL). Yield of isolated compounds. b Obtained as a mixture of E and Z isomers. c Mixture of MeOH:DCM (4:1) used. c Reaction performed 50 oC). SUMMARY OF THE INVENTION In one aspect, the present invention provides a novel manganese catalyst of Formula I or its isomeric forms, for hydrogenation of various substrates such as α,β-unsaturated ketones, aldehydes, and imines (of Formula IIA or IIB):
Formula I wherein,
Mn is manganese atom or manganese ion in oxidation state (I), moieties attached to Mn are selected from heteroaryl groups of pyridine and diazole, one or more carbon monoxide groups, and -PR3R4-NR2, wherein said nitrogen of -PR3R4-NR2 is attached to said heteroaryl, and X group; R1 is selected from the group consisting of hydrogen, alkyl, aryl, alkylaryl, alkoxy, cycloalkyl, alkyl cycloalkyl, and alkylcarboxy; R2 is selected from the group consisting of hydrogen, and alkyl; R3 is selected from the group consisting of alkyl, unsubstituted aryl, substituted aryl, and cycloalkyl; R4 is selected from the group consisting of alkyl, unsubstituted aryl, substituted aryl, and cycloalkyl; and X is selected from the group consisting of halides, organosulfonate oxoanion (Triflate), boron trifluoride, and tetrafluoroborate; wherein R1 and R2 may be identical or different, and R3 and R4 are the substituents of phosphine moiety. The present disclosure also provides a process of preparation of a novel manganese catalyst (Formula I) under mild conditions which comprises reacting compound of formula III with substituted pentacarbonylmanganese [Mn(CO)5X] at room temperature of 25 to 30 oC to yield a novel manganese catalyst (Formula I),
Formula III wherein R1, R2, R3, R4 and X are same as defined above under formula I. In another aspect, the present invention relates to a process of preparation of the manganese based catalyst complex of Formula I, the process comprising steps of: a) reacting a ligand compound of formula III with substituted pentacarbonylmanganese [Mn(CO)5X] with a solvent in a container to obtain a reaction mixture
Formula III wherein R1, R2, R3, R4 and X are same as defined above under formula I; b) stirring the reaction mixture of step a) under inert atmosphere at a temperature in the range of 27-80 oC for a time period of up to 48 hrs; c) purifying the mixture of step b) to obtain the manganese catalyst of Formula I. In an embodiment, the ligand compound of formula III used in step a) is selected from N-(diphenylphosphaneyl)-6-(1H-pyrazol-1-yl)pyridin-2-amine (L1), N-(di-n- propylphosphaneyl)-6-(1H-pyrazol-1-yl)pyridin-2-amine (L2), N-(di-tert- butylphosphaneyl)-6-(1H-pyrazol-1-yl)pyridin-2-amine (L3) and N-(di-tert- butylphosphaneyl)-N-methyl-6-(1H-pyrazol-1-yl)pyridin-2-amine (L4). In an embodiment, the solvent used in step a) is selected from tetrahydrofuran, 2-methyl tetrahydrofuran and toluene. In another aspect, the present invention provides a process for hydrogenation of substrate selected from α, β-unsaturated ketone, aldehyde and imine (of Formula IIA or IIB), by using the manganese based catalyst complex of Formula I, the process comprising steps of: (i) preparing a mixture of the substrate of Formula IIA or IIB in presence of Mn-catalyst of Formula I and a base in dry vial with stir bar
Formula IIA Formula IIB; wherein A, B, Y and X of formula IIA and R1, R2 and R3 of formula IIB is same as defined under formulas IVA and IVB; (ii) transferring the reaction vial of step i) in an autoclave under argon atmosphere; (iii) adding a polar solvent in vial of step ii) and pressurizing the autoclave with H2 gas followed by venting for five times; (iv) pressurizing the autoclave with H2 gas of pressure ranging between 5-50 bar, and stirring the mixture with speed of 500-800 rpm at temperature in the range of 27-50 ºC for time period of 1 to 24 hrs to obtain crude hydrogenated compound; and (v) purifying the crude compound of step iv) to obtain desired hydrogenated compounds of formula IV
or Formula IVA Formula IVB Wherein in formula IVA: X is oxo group (O) or nitrogen (NR1) group, where R1 is alkyl or aryl moiety; R is hydrogen, alkyl (C1-C10), (un)substituted aryl, (un)substituted heteroaryl, alkene, alkyne; A and Y is independently selected from hydrogen, alkyl (C1- C10), (un)substituted aryl, (un)substituted heteroaryl, alkene, alkyne, ferrocene, alkoxy, where the substituted aryl or heteroaryl maybe further substituted with aryl, alkoxy, alkyl, halogen, nitro, cyano, aryl ether, alkyl ether, aryl alkyl ether, CF3, (un)substituted amino, alkyl amino, aryl amino, ferrocene, alkoxy alkyl ether, alkyne alkyl ether, alkylene alkyl ether, hydroxyl, cyclic saturated or unsaturated ring of aryl or heteroaryl with number of rings from 0 to 4; B is selected from hydrogen, alkene, alkyne, alkyl, aryl, heteroaryl, ferrocene, halogen; and A and B optionally together may form saturated or unsaturated ring of aryl or heteroaryl which may further be substituted with hydrogen, alkyl, aryl, heteroaryl, hydroxyl, alkylhydroxyl, alkyl aryl ether, aryl alkyl ether, nitro, cyano, and halogen; and in formula IVB: X is oxo group (O) or nitrogen (NR3) group, where R3 is alkyl or aryl moiety; R1 is selected from hydrogen, alkyl (C1-C10), (un)substituted aryl, (un)substituted heteroaryl, alkene, alkyne, ferrocene, alkoxy, where the substituted aryl or heteroaryl maybe further substituted with aryl, alkoxy, alkyl, halogen, nitro, cyano, aryl ether, alkyl ether, aryl alkyl ether, CF3, (un)substituted amino, alkyl amino, aryl amino, ferrocene, alkoxy alkyl ether, alkyne alkyl ether, alkylene alkyl ether, hydroxyl, cyclic saturated or unsaturated ring of aryl or heteroaryl with number of rings from 0 to 4; R2 is selected from hydrogen, alkene, alkyne, alkyl, aryl, heteroaryl, ferrocene, halogen; and R1 and R2 optionally together may form saturated or unsaturated ring of aryl or heteroaryl which may further be substituted with hydrogen, alkyl, aryl, heteroaryl, hydroxyl, alkylhydroxyl, alkyl aryl ether, aryl alkyl ether, nitro, cyano, and halogen. In an embodiment, the novel hydrogenated compounds of formula IVA and/or IVB are selected from the group consisting of: (i) 1-(3-(Allyloxy)phenyl)-3-phenylpropan-1-one (2a)
, (ii) 3-Phenyl-1-(3-(prop-2-yn-1-yloxy)phenyl)propan-1-one (2b)
(iii) 1-(3-(Oxiran-2-ylmethoxy)phenyl)-3-phenylpropan-1-one (2c)
(iv) 2-(4-Acetylphenoxy)-1,3-diphenylpropan-1-one (2d)
. In an embodiment, the base used in said hydrogenation process is selected from the group consisting of potassium carbonate, potassium phosphate, potassium hydroxide, tripotassium phosphate potassium tert-butoxide, sodium tert-butoxide, sodium carbonate, cesium carbonate, sodium hydroxide, lithium carbonate, lithium hydroxide, calcium hydroxide, potassium bicarbonate, sodium bicarbonate, sodium methoxide, lithium bicarbonate and tertiary amines. In an embodiment, the polar solvent used in said hydrogenation process is selected from simple alcohols, such as C1-10 hydrocarbyl alcohol, saturated aliphatic C1-8alcohol, polyvalent alcohol; ether based solvent, aliphatic or aromatic hydrocarbon solvent, and halogenated hydrocarbon solvent, or mixtures thereof. In an embodiment, the purification of step v) of said hydrogenation process is done by concentrating the crude hydrogenated compound and subjecting it to column chromatography on silica gel wherein petroleum ether and ethyl acetate is used as solvent media in a ratio of 70:1 respectively, for separation and purification, to yield desired hydrogenated compounds of formula IVA or IVB. The Mn-catalyzed process for hydrogenation of present invention is not limited to process of hydrogenation of substrates such as ketones but may be applicable to
hydrogenation process of other substrates too e.g. alkenes, any carbonyl containing substrates, aldehydes and imides, etc. DETAILED DESCRIPTION OF THE INVENTION: “Alkyl” as used herein is collection of carbon atoms that are covalently linked together in normal, secondary, tertiary or cyclic arrangements, i.e., in linear, branched, cyclic arrangement or some combination thereof. An alkyl substituent to structure is chain of carbon atoms that is covalently attached to structure through sp3 carbon of substituent. The alkyl substituents, as used herein, contains one or more saturated moieties or groups and may additionally contain unsaturated alkyl moieties or groups, i.e., substituent may comprise one, two, three or more independently selected double bonds or triple bonds of combination thereof, typically one double or one triple bond if such unsaturated alkyl moieties or groups are present. Unsaturated alkyl moieties or groups include moieties or groups as described below for alkenyl, alkynyl, cycloalkyl, and aryl moieties. Saturated alkyl moieties contain saturated carbon atoms (sp3) and no aromatic, sp2 or sp carbon atoms. The number of carbon atoms in an alkyl moiety or group can vary and typically is 1 to about 50, e.g., about 1-30 or about 1-20, unless otherwise specified, e.g., C1-8 alkyl or C1-C8 alkyl means an alkyl moiety containing 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms and C1-6 alkyl or C1-C6 means an alkyl moiety containing 1, 2, 3, 4, 5 or 6 carbon atoms. When an alkyl substituent, moiety or group is specified, species may include methyl, ethyl, 1-propyl (n-propyl), 2-propyl (iso-propyl, —CH(CH3)2), 1-butyl (n-butyl), 2- methyl-1-propyl (iso-butyl, —CH2CH(CH3)2), 2-butyl (sec-butyl, —CH(CH3)CH2CH3), 2-methyl-2-propyl (t-butyl, —C(CH3)3), amyl, isoamyl, sec-amyl and other linear, cyclic and branch chain alkyl moieties. Unless otherwise specified, alkyl groups can contain species and groups described below for cycloalkyl, alkenyl, alkynyl groups, aryl groups, arylalkyl groups, alkylaryl groups and the like. Cycloalkyl as used herein is a monocyclic, bicyclic or tricyclic ring system composed of only carbon atoms. The term “cycloalkyl” encompasses a monocyclic or polycyclic aliphatic, non-aromatic radical, wherein each of the atoms forming the ring (i.e. skeletal atoms) is a carbon atom. The number of carbon atoms in an cycloalkyl substituent, moiety or group can vary and typically is 3 to about 50, e.g., about 1-30 or about 1-20, unless otherwise specified, e.g., C3-8 alkyl or C3-C8 alkyl means an cycloalkyl substituent, moiety or group containing 3, 4, 5, 6, 7 or 8 carbon atoms and C3-6 alkyl or
C3-C6 means an cycloalkyl substituent, moiety or group containing 3, 4, 5 or 6 carbon atoms. Cycloalkyl substituents, moieties or groups will typically have 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 carbon atoms and may contain exo or endo- cyclic double bonds or endo-cyclic triple bonds or a combination of both wherein the endo-cyclic double or triple bonds, or the combination of both, do not form a cyclic conjugated system of 4n+2 electrons; wherein the bicyclic ring system may share one (i.e., spiro ring system) or two carbon atoms and the tricyclic ring system may share a total of 2, 3 or 4 carbon atoms, typically 2 or 3. Unless otherwise specified, cycloalkyl substituents, moieties or groups can contain moieties and groups described for alkenyl, alkynyl, aryl, arylalkyl, alkylaryl and the like and can contain one or more other cycloalkyl moieties. Thus, cycloalkyls may be saturated, or partially unsaturated. Cycloalkyls may be fused with an aromatic ring, and the points of attachment to the aromatic ring are at a carbon or carbons of the cycloalkyl substituent, moiety or group that is not an aromatic ring carbon atom. Cycloalkyl groups include groups having from 3 to 10 ring atoms. Cycloalkyl substituents, moieties or groups include cyclopropyl, cyclopentyl, cyclohexyl, adamantly or other cyclic all carbon containing moieties. Cycloalkyls further include cyclobutyl, cyclopentenyl, cyclohexenyl, cycloheptyl and cyclooctyl. Cycloalkyl groups may be substituted or unsubstituted. Depending on the substituent structure, a cycloalkyl substituent can be a monoradical or a diradical (i.e., an cycloalkylene, such as, but not limited to, cyclopropan-1,1-diyl, cyclobutan-1,1-diyl, cyclopentan-1,1-diyl, cyclohexan-1,1-diyl, cyclohexan-1,4-diyl, cycloheptan-1,1-diyl, and the like). When cycloalkyl is used as a Markush group (i.e., a substituent) the cycloalkyl is attached to a Markush formula with which it is associated through a carbon involved in a cyclic carbon ring system carbon of the cycloalkyl group that is not an aromatic carbon. “Alkylamine” as used herein means —N(alkyl)xHy group, moiety or substituent where x and y are independently selected from group x=1, y=1 and x=2, y=O. Alkylamine includes—N(alkyl)xHy groups where x=2 and y=0 and alkyl groups taken together with nitrogen atom to which they are attached form a cyclic ring system. “Alkenyl” or “alkene” as used herein means a substituent, moiety or group that comprises one or more double bond moities (e.g., —CH═CH—) or 1, 2, 3, 4, 5 or 6 or more, typically 1, 2 or 3 such moieties and can include an aryl moiety or group such as
benzene, and additionally comprises linked normal, secondary, tertiary or cyclic carbon atoms, i.e., linear, branched, cyclic or any combination thereof unless the alkenyl moiety is a vinyl moiety (e.g., —CH═CH2). An alkenyl moiety, group or substituent with multiple double bonds may have the double bonds arranged contiguously (i.e. a 1, 3 butadienyl moiety) or non-contiguously with one or more intervening saturated carbon atoms or a combination thereof, provided that a cyclic, contiguous arrangement of double bonds do not form a cyclically conjugated system of 4n+2 electrons (i.e., aromatic). The number of carbon atoms in an alkenyl group or moiety can vary and typically is 2 to about 50, e.g., about 2-30 or about 2-20, unless otherwise specified, e.g., C2-8 alkenyl or C2-8 alkenyl means an alkenyl moiety containing 2, 3, 4, 5, 6, 7 or 8 carbon atoms and C2-6 alkenyl or C2-6 alkenyl means an alkenyl moiety containing 2, 3, 4, 5 or 6 carbon atoms. Alkenyl moieties or groups will typically have 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 carbon atoms. When an alkenyl moiety, group or substituent is specified, species include, by way of example and not limitation, any of the alkyl or cycloalkyl, groups moieties or substituents described herein that has one or more double bonds, methylene
methylmethylene (═CH—CH3), ethylmethylene (═CH—CH2—CH3), ═CH—CH2—CH2—CH3, vinyl (—CH═CH2), allyl, 1-methylvinyl, butenyl, iso-butenyl, 3-methyl-2-butenyl, 1-pentenyl, cyclopentenyl, 1-methyl-cyclopentenyl, 1-hexenyl, 3-hexenyl, cyclohexenyl and other linear, cyclic and branched chained all carbon containing moieties containing at least one double bond. When alkenyl is used as a Markush group (i.e., a substituent) the alkenyl is attached to a Markush formula with which it is associated through an unsaturated carbon of a double bond of the alkenyl moiety or group unless specified otherwise. “Alkynyl” or “alkyne” as used herein means a substituent, moiety or group that comprises one or more triple bond moieties (i.e., —C≡C—), e.g., 1, 2, 3, 4, 5, 6 or more, typically 1 or 2 triple bonds, optionally comprising 1, 2, 3, 4, 5, 6 or more double bonds, with the remaining bonds (if present) being single bonds and comprising linked normal, secondary, tertiary or cyclic carbon atoms, i.e., linear, branched, cyclic or any combination thereof, unless the alkynyl moiety is ethynyl. The number of carbon atoms in an alkenyl moiety or group can vary and typically is 2 to about 50, e.g., about 2-30 or about 2-20, unless otherwise specified, e.g., C2-8 alkynyl or C2-8 alkynyl means an alkynyl moiety containing 2, 3, 4, 5, 6, 7 or 8 carbon atoms. Alkynyl groups will
typically have 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 carbon atoms. When an alkynyl moiety or group is specified, species include, by way of example and not limitation, any of the alkyl moieties, groups or substituents described herein that has one or more double bonds, ethynyl, propynyl, butynyl, iso-butynyl, 3-methyl-2-butynyl, 1-pentynyl, cyclopentynyl, 1-methyl-cyclopentynyl, 1-hexynyl, 3-hexynyl, cyclohexynyl and other linear, cyclic and branched chained all carbon containing moieties containing at least one triple bond. When an alkynyl is used as a Markush group (i.e., a substituent) the alkynyl is attached to a Markush formula with which it is associated through one of the unsaturated carbons of the alkynyl functional group. “Aryl” as used here means an aromatic ring system or a fused ring system with no ring heteroatoms comprising 1, 2, 3 or 4 to 6 rings, typically 1 to 3 rings, wherein the rings are composed of only carbon atoms; and refers to a cyclically conjugated system of 4n+2 electrons (Huckel rule), typically 6, 10 or 14 electrons some of which may additionally participate in exocyclic conjugation (cross-conjugated (e.g., quinone). Aryl substituents, moieties or groups are typically formed by five, six, seven, eight, nine, or more than nine, carbon atoms. Aryl substituents, moieties or groups are optionally substituted. Exemplary aryls include C6-C10 aryls such as phenyl and naphthalenyl and phenanthryl. Depending on the structure, an aryl group can be a monoradical or a diradical (i.e., an arylene group). Exemplary arylenes include, but are not limited to, phenyl-1,2-ene, phenyl-1,3-ene, and phenyl-1,4-ene. When aryl is used as a Markush group (i.e., a substituent) the aryl is attached to a Markush formula with which it is associated through aromatic carbon of the aryl group. “Arylalkyl” as used herein means a substituent, moiety or group where an aryl moiety is bonded to an alkyl moiety, i.e., -alkyl-aryl, where alkyl and aryl groups are as described above, e.g., —CH2—C6H5 or —CH2CH(CH3)—C6H5. When arylalkyl is used as a Markush group (i.e., a substituent) the alkyl moiety of the arylalkyl is attached to a Markush formula with which it is associated through a sp3 carbon of the alkyl moiety. “Alkylaryl” as used herein means substituent, moiety or group where alkyl moiety is bonded to aryl moiety, i.e.,-aryl-alkyl, where aryl and alkyl groups are as described above, e.g. —C6H4—CH3 or —C6H4—CH2CH(CH3). When alkylaryl is used
as Markush group (i.e., substituent), aryl moiety of alkylaryl is attached to Markush formula with which it is associated through sp2 carbon of the aryl moiety. “Substituted alkyl”, “substituted cycloalkyl”, “substituted alkenyl”, “substituted alkynyl”, substituted alkylaryl”, “substituted arylalkyl”, “substituted heterocycle”, “substituted aryl” and the like as used herein mean alkyl, alkenyl, alkynyl, alkylaryl, arylalkyl heterocycle, aryl or other group or moiety as defined or disclosed herein that has substituent(s) that replaces hydrogen atom(s) or substituent(s) that interrupts carbon atom chain. Alkenyl and alkynyl groups that comprise substituent(s) are optionally substituted at carbon that is one or more methylene moieties removed from double bond. “Heterocycle” or “heterocyclic” or “heteroaryl” as used herein means a cycloalkyl or aromatic ring system wherein one or more, typically 1, 2 or 3, but not all of the carbon atoms comprising the ring system are replaced by a heteroatom which is an atom other than carbon, including, N, O, S, Se, B, Si, P, typically N, O or S wherein two or more heteroatoms may be adjacent to each other or separated by one or more carbon atoms, typically 1-17 carbon atoms, 1-7 atoms or 1-3 atoms. Heterocycles includes heteroaromatic rings (also known as heteroaryls) and heterocycloalkyl rings (also known as heteroalicyclic groups) containing one to four heteroatoms in the ring(s), where each heteroatom in the ring(s) is selected from O, S and N, wherein each heterocyclic group has from 4 to 10 atoms in its ring system, and with the proviso that the any ring does not contain two adjacent O or S atoms. Non-aromatic heterocyclic, substituents, moieties or groups (also known as heterocycloalkyls) have at least 3 atoms in their ring system and aromatic heterocyclic groups have at least 5 atoms in their ring system and include benzo-fused ring systems. Heterocyclics with 3, 4, 5, 6 and 10 atoms include aziridinyl azetidinyl, thiazolyl, pyridyl and quinolinyl, respectively. Nonaromatic heterocyclic substituents, moieties/groups are pyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothienyl, oxazolidinonyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl, thiomorpholinyl, thioxanyl, piperazinyl, aziridinyl, azetidinyl, oxetanyl, thietanyl, homopiperidinyl, oxepanyl, thiepanyl, oxazepinyl, diazepinyl, thiazepinyl, 1,2,3,6- tetrahydropyridinyl, pyrrolin-2-yl, pyrrolin-3-yl, indolinyl, 2H-pyranyl, 4H-pyranyl, dioxanyl, 1,3-dioxolanyl, pyrazolinyl, dithianyl, dithiolanyl, dihydropyranyl, dihydrothienyl, dihydrofuranyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, 3-
azabicyclo[3.1.0)hexanyl, 3azabicyclo[4.1.0)heptanyl, 3H-indolyl and quinolizinyl. Aromatic heterocyclic includes, by way of example and not limitation, pyridinyl, imidazolyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl, tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxazolyl, isothiazolyl, pyrrolyl, quinolinyl, isoquinolinyl, indolyl, benzimidazolyl, benzofuranyl, cinnolinyl, indazolyl, indolizinyl, phthalazinyl, pyridazinyl, triazinyl, isoindolyl, pteridinyl, purinyl, oxadiazolyl, thiadiazolyl, furazanyl, benzofurazanyl, benzo-thiophenyl, benzothiazolyl, benzoxazolyl, quinazolinyl, quinoxalinyl, naphthyridinyl and furopyridinyl. Non-aromatic heterocycles may be substituted with one or two oxo (═O) moieties and includes pyrrolidin-2-one. “Heteroaryl” as used herein means an aryl ring system wherein one or more, typically 1, 2 or 3, but not all of the carbon atoms comprising the aryl ring system are replaced by a heteroatom which is an atom other than carbon, including, N, O, S, Se, B, Si, P, typically, oxygen (—O—), nitrogen (—NX—) or sulfur (—S—) where X is —H, protecting group or C1-6 optionally substituted alkyl, wherein heteroatom participates in conjugated system either through pi-bonding with adjacent atom in ring system or through lone pair of electrons on heteroatom and may be optionally substituted on one or more carbons or heteroatoms, or combination of both, in manner which retains cyclically conjugated system. Examples of heteroaryls include by way of example and not limitation pyridyl, thiazolyl, pyrimidinyl, furanyl, thienyl, pyrrolyl, pyrazolyl, purinyl, imidazolyl, benzofuranyl, indolyl, isoindoyl, quinolinyl, isoquinolinyl, benzimidazolyl, pyridazinyl, pyrazinyl, benzothiopyran, benzotriazine, isoxazolyl, pyrazolopyrimidinyl, quinoxalinyl, thiadiazolyl, and triazolyl. Heterocycles that are not heteroaryls include, by way of example and not limited to, tetrahydrothiophenyl, tetrahydrofuranyl, indolenyl, piperidinyl, pyrrolidinyl, 2-pyrrolidonyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, octahydroisoquinolinyl, 2H-pyrrolyl, 3H-indolyl, 4H-quinolizinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, piperazinyl, quinuclidinyl, morpholinyl and oxazolidinyl. Monocyclic heteroaryls include, by way of example and not limitation, pyridinyl, imidazolyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl, tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxazolyl, isothiazolyl, pyrrolyl, pyridazinyl, triazinyl, oxadiazolyl, thiadiazolyl, and furazanyl. Heteroaryls include those substituents, moieties or groups containing 0-3 N atoms, 1-3 N atoms or 0-3 N atoms, 0-1 O atoms and 0-1 S atoms. A heteroaryl may be monocyclic or bicyclic. The ring system of a heteroaryls ring typically contains 1-9 carbons (i.e., C1-C9 heteroaryl). Monocyclic heteroaryls include
C1-C5 heteroaryls. Monocyclic heteroaryls include those having 5-membered or 6- membered ring systems. Bicyclic heteroaryls include C6-C9 heteroaryls. Depending on the structure, a heteroaryl group can be a monoradical or a diradical (i.e., a heteroarylene group). “Ether” as used herein in the terms “aryl ether, alkyl ether, aryl alkyl ether, alkoxy alkyl ether, alkyne alkyl ether, and alkylene alkyl ether” mean an organic moiety, group or substituent that comprises or consists of 1, 2, 3, 4 or more —O— moieties, usually 1 or 2, wherein no two —O— moieties are immediately adjacent (i.e., directly attached) to each other. Typically, ethers comprise an organic moiety containing 1-50 carbon atoms, 1-20 carbon atoms or 1-8 carbon atoms and 0 to 10 independently selected heteroatoms (e.g., O, S, N, P, Si), typically 0-2. An ether moiety, group or substituent includes organic moiety-O— wherein the organic moiety is as described herein for alkyl or optionally substituted alkyl group. When ether is used as a Markush group (i.e., a substituent) the oxygen of the ether functional group is attached to a Markush formula with which it is associated. When ether is a used as substituent in a Markush group it is sometimes designated as an “alkoxy” group. Alkoxy includes C1-C4 ether substituents such as, by way of example and not limited to, methoxy, ethoxy, propoxy, iso-propoxy and butoxy. Ether further includes those substituents, moieties or groups that contain one (excluding ketal) or more —OCH2CH2O—, moieties in sequence (polyethylene or PEG moieties). “Halogen” or “halo” as used herein means fluorine, chlorine, bromine or iodine. “Hydroxyl” as used herein means –OH, and the “alkylhydroxyl” means –OH is attached to alkyl groupl; wherein alkyl group is as defined above. “Haloalkyl” as used herein means an alkyl substituent moiety or group in which one or more of its hydrogen atoms are replaced by one or more independently selected halide atoms. Haloalkyl includes C1-C4 haloalkyl. Example but non-limiting C1-C4 haloalkyls are —CH2Cl, CH2Br, —CH2I, —CHBrCl, —CHCl—CH2Cl and —CHCl—CH2I. “Haloalkylene” as used herein means an alkylene substituent, moiety or group in which one or more hydrogen atoms are replaced by one or more halide atoms. Haloalkylene includes C1-C6 haloalkylenes or C1-C4 haloalkylenes. “Fluoroalkyl” as used herein means an alkyl in which one or more hydrogen atoms are replaced by a fluorine atom.
Fluoroalkyl includes C1-C6 and C1-C4 fluoroalkyls. Example but non-limiting fluoroalkyls include —CH3F, —CH2F2 and —CF3 and perfluroalkyls. “Fluoroalkylene” as used herein means an alkylene in which one or more hydrogen atoms are replaced by a fluorine atom. Fluoroalkylene includes C1-C6 fluoroalkylenes or C1-C4 fluoroalkylenes. The term “heteroalkyl” refers to an alkyl group in which one or more skeletal atoms of the alkyl are selected from an atom other than carbon, e.g., oxygen, nitrogen, sulfur, phosphorus or combinations thereof. In one aspect, a heteroalkyl is a C1-C6 heteroalkyl. As used herein, the term “alkylene”, employed alone or in combination with other terms, refers to a divalent alkyl linking group. Examples of alkylene groups include, but are not limited to, ethan-1,2-diyl, propan-1,3-diyl, propan-1,2-diyl, butan-1,4-diyl, butan-1,3- diyl, butan-1,2-diyl, 2-methyl-propan-1,3-diyl, and the like. As used herein, the term “alkoxy”, employed alone or in combination with other terms, refers to a group of formula —O-alkyl, wherein the alkyl group as defined above. Example alkoxy groups include but not limited to methoxy, ethoxy, propoxy (e.g., n- propoxy and isopropoxy), t-butoxy, and the like. As used herein, the term “alkylalkoxy”, employed alone or in combination with other terms, refers to a group of formula —alkyl- O-alkyl, wherein the alkyl group is as defined above. As used herein, the term “alkylamino” refers to a group of formula —NH(alkyl), wherein the alkyl group is as defined above. As used herein, the term “arylamino” refers to a group of formula —NH(aryl), wherein the aryl or aromatic group is as defined above. As used herein, the term “alkoxycarbonyl” refers to a group of formula —C(O)O-alkyl, wherein the alkyl group is as defined above. As used herein, the term “alkylcarbonylamino” refers to a group of formula — NHC(O)-alkyl, wherein the alkyl group is as defined above. As used herein, the term “alkylsulfonylamino” refers to a group of formula —NHS(O)2- alkyl, wherein the alkyl group is as defined above.
As used herein, the term “aminosulfonyl” refers to a group of formula —S(O)2NH2. As used herein, the term “alkylaminosulfonyl” refers to a group of formula — S(O)2NH(alkyl), wherein the alkyl group is as defined above. As used herein, the term “aminocarbonyl”, employed alone or in combination with other terms, refers to a group of formula —NHC(O)-. As used herein, the term “alkylaminocarbonyl”, employed alone or in combination with other terms, refers to a group of formula —alkyl-NHC(O)- or —NHC(O)-alkyl-. As used herein, the term “alkylacylamino”, employed alone or in combination with other terms, refers to a group of formula —alkyl-C(O)-alkyl/aryl/heteroparyl-NH2. As used herein, the term “aminocarbonylamino”, employed alone or in combination with other terms, refers to a group of formula —NHC(O)NH2. As used herein, the term “sulfanyl” or “thio” refers to a group of formula —SH. As used herein, the term “alkylthio” or “alkylsulfanyl” refers to a group of formula —S-alkyl, wherein the alkyl group is as defined above. As used herein, the term “arylthio” or “arylsulfanyl” refers to a group of formula —S-aryl, wherein the aryl group is as defined above. As used herein, the term “heteroarylthio” or “heteroarylsulfanyl” refers to a group of formula —S-heteroaryl, wherein the heteroaryl group is as defined above. As used herein, the term “sulfonyl” refers to a group of formula —S(O)2-. As used herein, the term “alkylsulfonyl” refers to a group of formula —S(O)2-alkyl, wherein the alkyl group is as defined above. As used herein, the term “arylsulfonyl” refers to a group of formula —S(O)2-aryl, wherein the aryl group is as defined above. As used herein, the term “heteroarylsulfonyl” refers to a group of formula —S(O)2-heteroaryl, wherein the heteroaryl group is as defined above. As used herein, the term “sulfonyloxy” refers to a group of formula —S(O)2-O-. As used herein, the term “alkylsulfonyloxy” refers to a group of formula —S(O)2-O-alkyl, wherein the alkyl group is as defined above. As used herein, the term “sulfinyl” refers to a group of formula —S(O)-. As used herein, the term “alkylsulfinyl” refers to a group of formula —S(O)-alkyl, wherein the alkyl group is as defined above. As used herein, the term “arylsulfinyl” refers to a group of formula —S(O)-aryl, wherein the aryl group is as defined above.
As used herein, the term “amino” refers to a group of formula —NH2. As used herein, the term “carbamyl” to a group of formula —C(O)NH2. As used herein, the term “carbonyl”, employed alone or in combination with other terms, refers to a —C(O)— group. As used herein, the term “alkylcarboxy” refers to a group of formula —C(O)OH connected with at least one of alkyl group. As used herein, the term “dialkylamino” refers to a group of formula —N(alkyl)2, wherein the two alkyl groups each is as defined above. As used herein, the term “alkyl cycloalkyl” refers to a group of formula —alkyl attached to cycloalkyl group, wherein the alkyl and cycloalkyl groups each are as defined above. As used herein, “haloalkoxy” refers to a group of formula —O-haloalkyl where alkyl and halo/halogen is as defined above. An example haloalkoxy group is OCF3. In some embodiments, the haloalkoxy group is fluorinated only. As used herein, the term “haloalkyl”, employed alone or in combination with other terms, refers to an alkyl group having from one halogen atom to 2 s+1 halogen atoms which may be the same or different, where “s” is the number of carbon atoms in the alkyl group, wherein the alkyl and halo is as defined above. As used herein, “haloaryl” refers to a group of formula — halo-aryl where aryl and halo/halogen is as defined above. The compounds described herein can be asymmetric (e.g., having one or more stereocenters). All stereoisomers, such as enantiomers, geometric isomers, and diastereomers, are intended unless otherwise indicated. Compounds of the present invention that contain asymmetrically substituted carbon atoms can be isolated in optically active or racemic forms. Methods on how to prepare optically active forms from optically inactive starting materials are known in the art, such as by resolution of racemic mixtures or by stereoselective synthesis. Many geometric isomers of olefins, C═N double bonds, and the like can also be present in the compounds described herein, and all such stable isomers are contemplated in the present invention. Cis and trans geometric isomers of the compounds of the present invention are described and may be isolated as a mixture of isomers or as separated isomeric forms. In some
embodiments, the compound has the (R)-configuration. In some embodiment, compound has (S)-configuration. The term, “compound,” used herein is meant to include all stereoisomers, geometric iosomers, tautomers, and isotopes of structures depicted. Compounds herein identified by name or structure as one particular tautomeric form are intended to include other tautomeric forms unless otherwise specified. All compounds, and pharmaceutically acceptable salts thereof, can be found together with other substances such as water and solvents (e.g. hydrates and solvates) or can be isolated. The expressions, “ambient temperature” and “room temperature” or “rt” as used herein, are understood in the art, and refer generally to a temperature, e.g. a reaction temperature, that is about the temperature of the room in which the reaction is carried out, for example, a temperature from about 20° C. to about 30° C. In general embodiment, the present invention relates to the mixed-donor (PN3N)Mn(I) complexes (catalyst of formula I) for the chemoselective hydrogenation of C=C, C=O and C=N bonds using 5 bar H2 and a mild base K3PO4 at room temperature (refer Figure 1). The notable features of the present invention are: (i) use of 3rd most abundant transition metal as a catalyst, (ii) excellent chemoselectivity in the reduction of C=C, C=O and C=N bonds, (iii) hydrogenation using 5 bar H2 and at room temperature (27 oC), (iv) use of mild base and atom-efficient H2 source, and (v) broad substrates scope with excellent tolerance of hydrogen-sensitive functionalities. In an embodiment, the present invention provides a manganese based catalyst complex of Formula I, for hydrogenation of substrate wherein the substrate is select from α, β- unsaturated ketone, aldehyde and imine (of Formula IIA or IIB); the formula I is represented by:
Formula I wherein,
Mn is manganese atom or manganese ion in oxidation state (I); moieties attached to said Mn are selected from heteroaryl rings, one or more carbon monoxide groups, -PR3R4-NR2 and X, wherein said nitrogen of -PR3R4-NR2 is further attached to said one of heteroaryl rings, and wherein said heteroaryl rings are selected from pyridine and diazole; wherein R1 is selected from the group consisting of hydrogen, (C1-C4)alkyl, aryl, alkyl aryl, alkoxy, cycloalkyl, alkyl cycloalkyl, and alkylcarboxy; R2 is selected from the group consisting of hydrogen and (C1-C4)alkyl; R3 is selected from group consisting of (C1-C4)alkyl, unsubstituted aryl, substituted aryl and cycloalkyl; R4 is selected from the group consisting of(C1-C4)alkyl, unsubstituted aryl, substituted aryl and cycloalkyl; and X is selected from the group consisting of halide, organosulfonate oxoanion (triflate), boron trifluoride, and tetrafluoroborate; wherein R1 and R2 may be identical or different, and R3 and R4 are substituents of phosphine moiety. In another embodiment, the Mn complex of formula I is defined by R1 being hydrogen, R2 being hydrogen or C1-C4alkyl, R3 being C1-C4alkyl or aryl, R4 being C1-C4alkyl or aryl, and X being halogen. Said Mn based catalyst comprises a mixed-donor ligand with different electronic features of donating center which suitably administer the electronic requirement at the metal center (Mn) and stabilize the active catalytic species. Moreover, the presence of NH on the side-arm could facilitate the non-innocent behavior of ligand via aromatization/dearomatization approach leading to the heterolytic activation of molecules. In another embodiment, the present disclosure provides a process of preparation of a novel manganese catalyst (Formula I) under mild conditions which comprising reacting compound of formula III and substituted pentacarbonylmanganese [Mn(CO)5X] at room temperature to yield a novel manganese catalyst (Formula I)
Formula III wherein R1, R2, R3, R4 and X are same as defined above under formula I.
In an additional embodiment, the present disclosure provides a process of preparation of novel manganese catalyst of Formula I, the steps comprising: a) reacting 0.16-0.24 mmol of compound of formula III with 0.16-0.24 mmol of substituted pentacarbonylmanganese [Mn(CO)5X] in a container such as round bottom flask with a solvent to obtain a reaction mixture
Formula III wherein R1, R2, R3, R4 and X are same as defined above under formula I; b) stirring the reaction mixture under inert atmosphere at temperature in the range of 27- 80 oC for a time period of up to 48 hrs; c) purifying the mixture to obtain the manganese catalyst of Formula I. In preferred embodiment, the compound of formula III used in step a) is selected from N- (di-tert-butylphosphaneyl)-6-(1H-pyrazol-1-yl)pyridin-2-amine (L3), N-(di-n- propylphosphaneyl)-6-(1H-pyrazol-1-yl)pyridin-2-amine (L2), N- (diphenylphosphaneyl)-6-(1H-pyrazol-1-yl)pyridin-2-amine (L1), and N-(di-tert- butylphosphaneyl)-N-methyl-6-(1H-pyrazol-1-yl)pyridin-2-amine (L4). In another preferred embodiment, the solvent used in step a) is selected from THF (tetrahydrofuran), 2-methyl THF, and toluene. In another preferred embodiment, the amount of compound of formula III used in the reaction is inert atmosphere in step a) is attained by argon or helium. In yet another preferred embodiment, the amount of compound of formula III used in the reaction is 0.16 mmol, 0.20 mmol or 0.24 mmol. In yet another preferred embodiment, amount of compound of formula III and substituted pentacarbonylmanganese used in reaction is 0.16 mmol, 0.20 mmol or 0.24 mmol respectively.
In another embodiment, the novel manganese catalyst (Formula I) for hydrogenation of α, β-unsaturated ketones, aldehydes and imines (of Formula IIA or IIB), is selected from group consisting of: 1. N-(diphenylphosphaneyl)-6-(1H-pyrazol-1-yl)pyridin-2-amine-Mn(CO)2Br complex(1a) (Mn-1)
2. N-(di-iso-propylphosphaneyl)-6-(1H-pyrazol-1-yl)pyridin-2-amine-Mn(CO)2Br complex (1b) (Mn-2)
3. N-(di-tert-butylphosphaneyl)-6-(1H-pyrazol-1-yl)pyridin-2-amine Mn(CO)2Br complex (1c) (Mn-3)
4. N-(di-tert-butylphosphaneyl)-N-methyl-6-(1H-pyrazol-1-yl)pyridin-2-amine Mn(CO)2Br complex (1d) (Mn-4)
. Interestingly considering the characterization data of all complexes Mn-1 to Mn-3 and 1d, it displayed three IR peaks for carbonyls ranging between 1857-2053 cm-1. Similarly, closer look at the 13C{1H}-NMR spectra of complexes indicate the three carbonyl signals. Moreover,
and 13C{1H}-NMR spectra of all complexes display two sets of peaks. All these observations support formation of two geometrical isomeric species in each complex Mn-1, Mn-2, Mn-3 and 1d. Considering presence of three signals for carbonyls in each complexes, inventors noted that one isomer of Mn-complex would
have two carbonyls that are trans to –Br and –Npy ligands accounting for two peaks (as indicated in X-ray structure), whereas the other isomer would have two carbonyls trans to each other and display a single carbonyl peak (refer, Figure 2). All the complexes are further characterized by ESI-MS that show two prominent isotopic masses for 79Br and 81Br containing complexes. The molecular structure of Mn-2 was confirmed by a single crystal X-ray study (Figure 3). As expected, the coordination geometry around the manganese is distorted octahedral with –Br and one –CO unit trans to each other, making the C9 ^Mn1 ^Br angle almost linear (175.54(15)o). Mn1 ^C10 bond length [1.797(4) Å] is slightly longer than Mn1 ^C9 bond length [1.773(4) Å], which is due to greater trans influence of –Npy than –Br. The process for hydrogenation of various substrates such as α, β-unsaturated ketones, aldehydes, and imines (of Formula IIA or IIB) by using a novel manganese catalyst (Formula I) are successfully done and represented in detail in figures 3 and 4. These figures 3 and 4 enlist the hydrogenated compounds from substrates using said manganese catalyst (Formula I) namely compounds 4 to 55 with yields ranging from 33 to 97% or 60 to 97% of yield. The characterization data for these compounds 4-55 are well determined using 1H-NMR, C13-NMR and HRMS, and the same are in line with the data as reported in the literature known reports. In another embodiment of present invention, a substrate i.e. α, β-unsaturated ketones, aldehyde, ketone or imine (of Formula IIA or IIB) is hydrogenated to yield hydrogenated product (Formula IV),
Formula IV wherein X is oxo group (O) or or nitrogen (NR1) group, where R1 is alkyl or aryl moiety; R is hydrogen, alkyl (C1-C10), (un)substituted aryl, (un)substituted heteroaryl, alkene, alkyne; A and Y is independently selected from hydrogen, alkyl (C1-C10), (un)substituted aryl, (un)substituted heteroaryl, alkene, alkyne, ferrocene, alkoxy, where the substituted aryl or heteroaryl maybe further substituted with aryl, alkoxy, alkyl, halogen, nitro, cyano,
aryl ether, alkyl ether, aryl alkyl ether, CF3, (un)substituted amino, alkyl amino, aryl amino, ferrocene, alkoxy alkyl ether, alkyne alkyl ether, alkylene alkyl ether, hydroxyl, cyclic saturated or unsaturated ring of aryl or heteroaryl with number of rings from 0 to 4; B is selected from hydrogen, alkene, alkyne, alkyl, aryl, heteroaryl, ferrocene, halogen; and A and B together may form saturated or unsaturated ring of aryl or heteroaryl which may further be substituted with hydrogen, alkyl, aryl, heteroaryl, hydroxyl, alkylhydroxyl, alkyl aryl ether, aryl alkyl ether, nitro, cyano, halogen. The hydrogenated products catalyzed by the novel manganese catalyst (Formula I) of α,β-unsaturated ketones, aldehydes, and imines (of Formula IIA or IIB) is selected from group consisting of: (i) 1-(3-(Allyloxy)phenyl)-3-phenylpropan-1-one (2a)
(ii) 3-Phenyl-1-(3-(prop-2-yn-1-yloxy)phenyl)propan-1-one (2b)
(iii) 1-(3-(Oxiran-2-ylmethoxy)phenyl)-3-phenylpropan-1-one (2c)
(iv) 2-(4-Acetylphenoxy)-1,3-diphenylpropan-1-one (2d)
In preferred embodiment, the present disclosure provides a process for hydrogenation of various substrates such as α, β-unsaturated ketones, aldehydes, and imines (of Formula IIA or IIB) by using a novel manganese catalyst (Formula I) comprises of: (i) Reacting a substrate such as α, β-unsaturated ketones (Formula IIA) in presence of Mn-catalyst (Formula I) (1-5 mol%), base (2-10 mol%) in dry vial with stir bar, inside the glove box;
(ii) Transferring the reaction vial to an autoclave under argon atmosphere; (iii) Adding polar solvent and pressurizing autoclave with H2 (5-50 bar) and venting for five times; (iv) Pressurizing the autoclave with 5-50 bar H2 and stirring (500-800 rpm) at room temperature (27-50 oC) for 1-24 h; (v) After reaction time, the reaction mixture is concentrated and subjected to column chromatography on silica gel wherein petroleum ether and ethyl acetate is present in the ratio of 70:1 respectively, after separation and purification, to yield desired hydrogenated products. The base is selected from the group consisting of potassium carbonate, potassium phosphate, potassium hydroxide, potassium tert-butoxide, sodium tert-butoxide, sodium carbonate, cesium carbonate, sodium hydroxide, lithium carbonate, lithium hydroxide, calcium hydroxide, potassium bicarbonate, sodium bicarbonate, sodium methoxide, lithium bicarbonate and tertiary amines, most preferably base used in the present invention is Tripotassium phosphate. Solvents used in the present invention include simple alcohols, such as C1-10 hydrocarbyl alcohols, often saturated aliphatic C1-8alcohols, for example, ethanol, isopropanol and tert-butanol; polyvalent alcohols such as ethylene glycol, propylene glycol, 1,2-propanediol and glycerol; ethers, for example tetrahydrofuran (THF) 1,4- dioxane, methyl tert-butyl ether, cyclopentyl methyl ether; aliphatic and aromatic hydrocarbon solvents, for example C5-12alkanes, benzene, toluene and xylene and halogenated (typically chlorinated) hydrocarbon solvents, for example dichloromethane and chlorobenzene, or mixtures thereof, in particular, mixtures of alcohols, for example ethanol or isopropanol, and hydrocarbon solvents such as hexanes, xylenes (i.e. isomeric mixtures) or toluene. According to particular embodiments of present invention, methanol is used as a solvent. Suitable temperature to conduct the reaction at step i) is in the range of 20 °C-40 °C. In particularly useful embodiment, reaction at step i) is conducted at 27°C and the duration of hydrogenation reaction is quite low, preferably time requires is 1 hour to 5 hours. The methods of the invention, as is typical for hydrogenation reactions, are conducted in the presence of hydrogen gas, under pressure. Generally, the pressure at which the reactions are conducted is in the range of about 1 bar (100 kPa) to about 100 bar (10,000
kPa), for example from about 20 bar (2,000 kPa) to about 80 bar (8,000 kPa), although higher or lower pressures may on occasion be convenient, pressure at which hydrogenation reaction of the present invention is carried out is much lower, 5 bar. According to one aspect of the present invention, catalyzing the hydrogenation of various substrates especially ketones require low catalyst loading. According to one aspect of present invention, compound comprising a charged or neutral complex of formula (I), wherein —N is substituted one or more times with the second electron donating group and at least one of R1 and R2 are substituted one or more times with the first electron donating group. According to one aspect of the present invention, form of Mn-catalyst and compound of Formula (I) is amorphous. The Mn catalyst with an acidic NH on the ligand backbone. This acidic NH initiate the catalytic process by the aromatization/dearomatization process and make the present system the best catalysts at room temperature. It also selectively hydrogenates one double bond over the other. According to one aspect of the present invention, ligands are tridentate attached to Mn complex represents tridentate neutral or anionic ligand. Specifically, the present invention provides a chemoselective hydrogenation of C=C, C=O and C=N bonds in α,β-unsaturated ketones, aldehydes and imines at room temperature using the Mn catalyst of formula I at 5.0 bar H2. Amongst the Mn catalysts disclosed, the tBu-substituted complex Mn(CO)2Br shows an exceptional chemoselective catalytic reduction of unsaturated bonds in a wide range of α,β-unsaturated ketones/aldehydes/imines. This hydrogenation tolerates a range of highly sensitive functionalities, such as halides (-F, -Cl, -Br, -I), alkoxy, hydroxy and epoxide, including hydrogen sensitive moieties like acetyl, nitrile, nitro, unconjugated alkenyl and alkynyl groups. C=C bond is chemoselectively hydrogenated in α,β-unsaturated ketones, whereas aldehyde’s C=O bond and imine’s C=N bond are preferentially reduced over C=C bond using developed Mn catalyst. Comprehensive mechanistic investigation by controlled studies endorsed the non- innocent behaviour of ligand in the Mn-catalyst and supported a de-
aromatization/aromatization pathway by retaining the oxidation state of Mn(I). The DFT energy calculations highlighted a probable rate-influencing H2 activation with facile progress of other elementary steps. Particularly, the H2 provided a hydride-source and solvent alcohol (e.g. MeOH, propanol, etc.) gave proton-source for the hydrogenation reaction. Proposed mechanistic cycle was unanimously supported by the DFT energy calculations. In a nutshell, the present invention provides an efficient protocol for the chemoselective hydrogenation of C=C, C=O and C=N bonds in α,β-unsaturated ketones, aldehydes and imines catalyzed by the well-defined pincer-ligated Mn(I) complex of formula I. The employment of a mild base, moderate H2 pressure and room temperature (27 oC) in the Mn-catalyzed hydrogenation are highly advantageous to the commonly employed KOtBu base and extreme reaction conditions. The mixed donor Mn(I) complexes of formula I, ^3-(R2PN3NPyz)Mn(CO)2Br (R = Ph, iPr, tBu) were synthesized and meticulously characterized by various techniques. Though both the iPr and tBu-substituted Mn(I) complexes are efficient for the hydrogenation of α,β-unsaturated ketones, the (tBu2PNNPyz)Mn(CO)2Br complex as a catalyst provided exceptional chemoselectivity for the reduction of C=C bond (1,4-hydrogen addition). Thus, using the beneficial molecular hydrogen and a mild K3PO4 base, the (tBu2PNNPyz)Mn(I) catalyst could hydrogenate diverse unsaturated ketones to saturated ketones at room temperature with the compatibility of sensitive functionalities, such as halides ( ^F, ^Cl, ^Br, ^I), alkoxy, hydroxy, epoxide, acetyl, nitrile, nitro, unconjugated alkenyl and alkynyl groups. The C=O bond in aldehydes and C=N bond in imines were preferentially hydrogenated (1,2- hydrogen addition) over the C=C bond using the Mn-3 catalyst. EXAMPLES The ligand precursor 6-(1H-pyrazol-1-yl)pyridin-2-amine, ligands L1 and L3 were prepared according to the previously described procedures (refer, D. Gong et al., J. Mol. Catal. A Chem., 2014, 395, 100-107; H. Chen et al., Polym. Chem., 2017, 8, 1805-1814; and D. Gong et al., Dalton Trans., 2016, 45, 19399-19407) Example 1: Synthesis of N-(di-iso-propylphosphaneyl)-6-(1H-pyrazol-1-yl)pyridin- 2-amine (L2): In 50 mL oven dried Schlenk flask, 6-(1H-pyrazol-1-yl)pyridin-2-amine (0.20 g, 1.25 mmol) was dissolved in THF (10 mL) followed by addition of freshly
distilled Et3N (0.21 S4 mL, 1.5 mmol) under inert atmosphere. Reaction mixture was cooled to 0ºC and chlorodiisopropylphosphine (0.21 g, 1.37 mmol) was added dropwise. The reaction mixture was allowed to room temperature and stirred for 1 h. Further reaction mixture was cooled to -78ºC and n-BuLi (0.94 mL, 1.5 mmol; 1.6 M in THF) was added dropwise resulting in colorless solution. Then reaction was allowed to room temperature and stirred for 1 h, followed by heating at 60 ºC for 16 h. Volatiles were evaporated under vacuum and 30 mL of toluene was added into it. Filtration and evaporation of toluene extract gave N-(diiso-propylphosphaneyl)-6-(1H-pyrazol-1- yl)pyridin-2-amine (L2; 0.27 g, 78%) as colorless liquid.1H-NMR (500 MHz, C6D6): δ = 8.65 (d, J = 2.1 Hz, 1H, Ar–H), 7.68-7.66 (m, 2H, Ar–H), 7.13 (t, J = 8.1 Hz, 1H, Ar– H), 6.95 (dd, J = 7.9, 2.2 Hz, 1H, Ar–H), 6.14 (dd, J = 2.4, 1.5 Hz, 1H), 4.55 (br s, 1H, NH), 1.41 (d sept, J = 6.9, 1.7 Hz, 2H, CH), 0.90 (dd, J = 16.2, 7.3 Hz, 6H, CH3), 0.86 (dd, J = 11.0, 7.0 Hz, 6H, CH3). 13C{1H}-NMR (125 MHz, C6D6): δ = 160.4 (d, J = 20.0 Hz, Cq), 151.4 (Cq), 142.2 (CH), 140.6 (CH), 127.0 (CH), 107.7 (CH), 106.4 (d, J = 17.2 Hz, CH), 103.0 (CH), 26.8 (d, J = 12.4 Hz, 2C, CH), 19.2 (CH3), 19.0 (CH3), 17.5(CH3), 17.4(CH3).31P{1H}-NMR(162 MHz, C6D6):48.6 (s). Example 2: N-(Di-tert-butylphosphaneyl)-N-methyl-6-(1H-pyrazol-1-yl)pyridin-2- amine (L4): In 50 mL round bottom flask, N-(di-tert-butylphosphaneyl)-6-(1H-pyrazol- 1- yl)pyridin-2-amine (0.10 g, 0.33 mmol) in THF (5 mL) was cooled to -20 oC and n- BuLi (0.25 mL, 0.40 mmol; 1.6 M in hexane) was added followed by the addition of MeI (0.055 g, 0.39 mmol). The reaction mixture was allowed to the room temperature and stirred for overnight. The volatiles were evaporated under vacuo and 20 mL of water was added. The organic layer was extracted in EtOAc and the crude product was subjected to the column chromatography on silica gel (petroleum ether/EtOAc:10/1) to yield L3Me (0.071 g, 68%) as white solid.1H-NMR (500 MHz, CDCl3): δ = 8.30 (d, J = 2.4 Hz, 1H, Ar–H), 7.66 (s, 1H, Ar–H), 7.36 (dt, J = 7.9, 2.1 Hz, 1H, Ar–H), 7.04 (d, J = 7.5 Hz, 1H, Ar–H), 6.51 (d, J = 8.1 Hz, 1H), 6.37 (t, J = 2.1 Hz, 1H, Ar–H), 1.83 (d, J = 11.1 Hz, 3H, CH3), 1.34 (d, J = 14.1 Hz, 18H, CH3). 13C{1H}-NMR (100 MHz, CDCl3): δ = 164.4 (d, J = 9.2 Hz, Cq), 149.8 (Cq), 140.9 (CH), 138.6 (d, J = 3.8 Hz, CH), 126.3 (CH), 116.1 (d, J = 22.1 Hz, CH), 106.5 (CH), 98.5 (CH), 36.4 (d, J = 65.6 Hz, 2C, Cq), 27.2 (6C, CH3), 5.6 (d, J = 42.0 Hz, CH3).31P{1H}- NMR (162 MHz, CDCl3): 36.9 (s) Example 3: Synthesis and characterization of Mn-catalyst (1a)(Mn-1):
In a 25 mL round bottom flask N-(diphenylphosphaneyl)-6-(1H-pyrazol-1-yl)pyridin-2- amine (L1, 0.084 g, 0.24 mmol) and Mn(CO)5Br (0.067 g, 0.24 mmol) was added inside the glove box. The reaction flask was taken out and THF (3 mL) was added. Reaction mixture was stirred under inert atmosphere at room temperature (27 ºC) for 20 h. Within this time complex has been precipitated out. The solvent was evaporated under vacuum and solid was washed with hexane (3 mL X 3 times) and dried under vacuum to give yellow powder of Mn-1 complex (0.090 g, 70 %). FT-IR (νCO, cm-1): 1935, 1865, 1857. 1H-NMR (500 MHz, DMSOd6): (one isomer): δ = 10.34 (br s, 1H), 9.15 (br s, 1H), 8.57 (br s, 1H), 8.10 (br s, 1H), 7.77- 7.42 (m, 11H), 7.28 (br s, 1H), 6.92 (br s, 1H); (other isomer): δ = 10.02 (br s, 1H), 8.99 (br s, 1H), 8.22 (br s, 1H), 7.96 (br s, 1H), 7.77- 7.42 (m, 11H), 7.16 (br s, 1H), 6.77 (br s, 1H). 13C{1H}-NMR (125 MHz, DMSO-d6): (for both isomers) δ = 229.3, 225.3, 223.8, 160.0, 147.4, 146.1, 144.9, 141.5, 139.9, 136.2, 130.9, 129.8, 129.5, 128.9, 128.1, 127.7, 127.0, 125.7, 110.9, 106.7, 99.3. 31P NMR (162 MHz, DMSO-d6, ppm): 136.89 (s), 134.54 (s). ESI-MS (–ve mode): m/z [M– H]– Calcd for [C22H17 79BrMnN4O2P–H] 532.9569, Found 532.9575; m/z [M–H]– Calcd for [C22H1781BrMnN4O2P–H] 534.9549, Found 534.9554. Example 4: Synthesis and characterization of Mn-catalyst (1c)(Mn-2):
This catalyst was synthesized following the procedure similar to the synthesis of Mn-1 (example 1), using N-(di-iso-propylphosphaneyl)-6-(1Hpyrazol-1-yl)pyridin-2-amine (L2; 0.060 g, 0.217 mmol) and Mn(CO)5Br (0.060 g, 0.218 mmol). The complex Mn-2 was obtained as an orange powder. Yield: 0.090 g (89%). FT-IR (νCO, cm-1): 1940, 1872, 1857. 1H-NMR (400 MHz, DMSO-d6): (one isomer): δ = 9.15 (br s, 1H), 8.92 (br s, 1H), 8.49 (br s, 1H), 7.94 (br s, 1H), 7.53 (br s, 1H), 7.03 (br s, 1H), 6.91 (br s, 1H), 1.30-1.18 (m, 14H); (other isomer): δ = 9.13 (br s, 1H), 8.80 (br s, 1H), 8.10 (br s, 1H), 7.79 (br s, 1H), 7.40 (br s, 1H), 6.91 (br s, 1H), 6.72 (br s, 1H), 1.18-1.09 (m, 14H). 13C{1H}-NMR (100 MHz, DMSO-d6): (one isomer): δ = 230.2 (d, J = 15.3 Hz, CO),
226.6 (d, J = 22.9 Hz, CO), 161.0 (d, J = 9.5 Hz, Cq), 147.4 (Cq), 146.1 (CH), 141.1 (CH), 130.9 (CH), 111.4 (CH), 106.5 (CH), 98.8 (CH), 29.7, 26.4, 18.1, 17.4; (other isomer): δ = 227.0 (d, J = 19.1 Hz, CO), 225.8 (d, J = 22.9 Hz, CO), 160.6 (d, J = 9.5 Hz, Cq), 147.4 (Cq), 144.3 (CH), 139.5 (CH), 129.3 (CH), 110.6 (CH), 105.2 (CH), 98.1 (CH), 26.5, 25.8, 17.3, 16.5. 31P{1H}-NMR (162 MHz, DMSO-d6, ppm): 159.8 (s), 158.4 (s). ESI-MS (–ve mode): m/z [M–H]– Calcd for [C16H21 79BrMnN4O2P–H] 464.9882, Found 464.9887; m/z [M–H]– Calcd for [C16H21 81BrMnN4O2P–H] 466.9862, Found 466.9866. Example 5: Synthesis and characterization of Mn-catalyst (1c) (Mn-3)
In a 25 mL round bottom flask N-(di-tert-butylphosphaneyl)-6-(1H-pyrazol-1-yl)pyridin- 2-amine (L3, 0.050 g, 0.16 mmol) and Mn(CO)5Br (0.045 g, 0.16 mmol) was added inside the glove box. The reaction flask was taken out and THF (3 mL) was added. Reaction mixture was stirred under inert atmosphere at room temperature (27 oC) for 48 h. By the time the color of reaction mixture was changed from yellow to red. The reaction mixture was concentrated to 0.5 mL. Then hexane was added through the wall to give the orange precipitate of the desired complex. Then the solid was washed with hexane (10 mL x 3 times) and dried under vacuum to give orange solid of complex (0.064 g, 82 %). Note: The synthesized Mn-3 is sensitive to light, hence stored in brown colored vial. FT-IR (νCO, cm-1): 2053, 1959, 1930.31P NMR (162 MHz, CD2Cl2, ppm): 178.51 (s), 175.26 (s).31P NMR (162 MHz, CD3OD, ppm): 176.62 (s), 171.27 (s). 1H- NMR (200 MHz, CD3OD): δ = 8.46 (d, J = 24.3 Hz, 1H, Ar–H), 7.79 (s, 1H, Ar–H), 7.56 (s, 1H, Ar–H), 7.07 (s, 1H, Ar–H), 6.75 (s, 1H, Ar–H), 6.44 (d, J = 18.3 Hz, 1H, Ar–H), 2.95 (s, 1H, NH), 0.96 (t, J = 14.5 Hz, 18H, CH3). ESI-MS (–ve mode): m/z [M– H]– Calcd for [C18H25 79BrMnN4O2P–H] 493.0195, Found 493.0197; m/z [M–H]– Calcd for [C18H25 81BrMnN4O2P–H] 495.0175, Found 495.0178. Elemental anal. Calcd for C18H25BrMnN4O2P: C, 43.66; H, 5.09; N, 11.31. Found: C, 43.37; H, 5.26; N, 11.04. IR (νCO, cm-1): 1959, 1930. Example 6: Synthesis and characterization of Mn-catalyst (1d) (Mn-4):
This complex was synthesized following the procedure similar to the synthesis of Mn-1, using N-(di-tert-butylphosphaneyl)-N-methyl-6- (1H-pyrazol-1-yl)pyridin-2-amine (L4, 0.042 g, 0.132 mmol) and Mn(CO)5Br (0.036 g, 0.131 mmol), and the reaction mixture was stirred at room temperature (27 ºC) for 16 h. The complex Mn-3Me was obtained as an orange powder. Yield: 0.060 g (85%). FT-IR (νCO, cm1 ): 2018, 1924, 1901. 1H- NMR (500 MHz, acetone-d6): δ = 8.67 (br s, 1H, Ar–H), 8.21 (br s, 1H, Ar–H), 7.45 (br s, 1H, Ar–H), 7.02 (br s, 1H, Ar–H), 6.73 (br s, 1H, Ar–H), 6.63 (br s, 1H, Ar–H), 1.93 (s, 3H, CH3), 1.43 (d, J = 12.8 Hz, 18H, CH3).13C{1H}-NMR (125 MHz, DMSO-d6): δ = 224.2 (CO), 223.9 (CO), 223.1 (CO), 164.9 (Cq), 148.3 (Cq), 144.0 (CH), 138.1 (CH), 129.7 (CH), 112.0 (CH), 110.5 (CH), 96.4 (CH), 36.2 (d, J = 63.6 Hz, 2C Cq), 25.8 (d, J = 30.5 Hz, 6C, CH3), 5.1 (d, J = 42.0 Hz, CH3). 31P{1H}-NMR (162 MHz, acetoned6): 41.5 (s). Example 7: General procedure for hydrogenation of substrates. A substrate such as α, β-unsaturated ketones or aldehydes or imines (of Formula IIA or IIB) in presence of Mn-catalyst (Formula I) (5mol%), base (10 mol%) was reacted in dry vial with stir bar, inside the glove box. Reaction vial was transferred to autoclave under argon atmosphere. Polar solvent was added and pressurized autoclave with H2 (5 bar) and vented for five times. The autoclave was pressurized with 5 bar H2 and stirred (700 rpm) at 27 oC for 1 h. After reaction time, reaction mixture was concentrated and subjected to column chromatography on silica gel where petroleum ether & ethyl acetate was used in ratio of 70:1, after separation and purification, yielded desired hydrogenated products. Table 1. Optimization of Reaction Parameters
aReaction Conditions: 4a (0.042 g, 0.20 mmol), base (0.02 mmol), [Mn] catalyst (0.01 mmol, 5 mol %), solvent (1.0 mL). bGC conversion, isolated yield is given in parentheses. c20% allylic alcohol was observerd. dUsing 6.0 mol% K3PO4. eUsing 3 mol% of Mn-3. fUsing 3 mol% of Mn-3 and 6 mol% of K3PO4. bpy = 2,2’-bipyridine, phen = 1,10-phenanthroline, dppf = 1,1′-bis(diphenylphosphino)ferrocene, dppbz = 1,2- bis(diphenylphosphino)benzene. All three manganese complexes contain mixture of two geometrical isomers. Example 8: Synthesis of 1,3-diphenylpropan-1-one: To a dry vial with stir bar was introduced catalyst I (0.005 g, 0.01 mmol), K3PO4 (0.0043 g, 0.02 mmol), and (E)-chalcone (0.042 g, 0.202 mmol) inside the glove box. The reaction vial was transferred to an autoclave under argon atmosphere. Then MeOH (1.0 mL) was added and the autoclave was pressurized with H2 (5 bar) and vented for five times. Finally, the autoclave was pressurized with 5 bar H2 and stirred (700 rpm) at room temperature (27 oC) for 1 h. After reaction time, the reaction mixture was concentrated and subjected to column chromatography on silica gel (petroleum ether/EtOAc: 70/1) to yield 1,3-diphenylpropan-1-one (0.041 g, 97%) as white solid. 1H-NMR (500 MHz,
CDCl3): δ = 7.95 (d, J = 7.4 Hz, 2H, Ar–H), 7.54 (t, J = 7.4 Hz, 1H, Ar–H), 7.44 (t, J = 7.6 Hz, 2H, Ar–H), 7.31-7.18 (m, 5H, Ar–H), 3.29 (t, J = 7.7 Hz, 2H, CH2), 3.06 (t, J = 7.7 Hz, 2H, CH2).13C{1H}-NMR (125 MHz, CDCl3): δ = 199.4 (CO), 144.4 (Cq), 137.0 (Cq), 133.2 (CH), 128.8 (2C, CH), 128.7 (2C, CH), 128.6 (2C, CH), 128.2 (2C, CH), 126.3 (CH), 40.6 (CH2), 30.3 (CH2). HRMS (ESI): m/z Calcd for C15H14O + H+ [M + H]+ 211.1117; Found 211.1115. Example 9: Synthesis of 1-(3-(Allyloxy)phenyl)-3-phenylpropan-1-one (2a) (15): The representative procedure was followed, using substrate (E)-1-(3-(allyloxy)phenyl)-3- phenylprop-2-en-1-one (0.053 g, 0.201 mmol) and the reaction mixture was stirred at room temperature (27 oC) for 3 h. Purification by column chromatography on silica gel (petroleum ether/EtOAc: 50/1) yielded 1-(3-(Allyloxy)phenyl)-3-phenylpropan-1-one (0.039 g, 73%) as yellow oil.1H-NMR (400 MHz, CDCl3): δ = 7.54 (d, J = 7.8 Hz, 1H, Ar–H), 7.51-7.50 (m, 1H, Ar–H), 7.35 (t, J = 7.9 Hz, 1H, Ar–H), 7.30 (t, J = 7.3 Hz, 2H, Ar–H), 7.26-7.19 (m, 3H, Ar–H), 7.12 (dd, J = 8.3, 2.0 Hz, 1H, Ar–H), 6.10-6.01 (m, 1H, CH), 5.43 (dd, J = 17.3, 1.5 Hz, 1H, CH), 5.31 (dd, J = 10.6, 1.4 Hz, 1H, CH), 4.57 (d, J = 5.3 Hz, 2H, CH2), 3.28 (t, J = 7.7 Hz, 2H, CH2), 3.06 (t, J = 7.6 Hz, 2H, CH2). 13C{1H}-NMR (100 MHz, CDCl3): δ = 199.4 (CO), 159.3 (Cq), 141.7 (Cq), 138.7 (Cq), 133.3 (CH), 130.1 (CH), 129.0 (2C, CH), 129.0 (2C, CH), 126.6 (CH), 121.3 (CH), 120.6 (CH), 118.4 (CH2), 113.8 (CH), 69.4 (CH2), 41.0 (CH2), 30.6 (CH2). HRMS (ESI): m/z Calcd for C18H18O2 + H+ [M + H]+ 267.1380; Found 267.1373. Example 10: Synthesis of 3-Phenyl-1-(3-(prop-2-yn-1-yloxy)phenyl)propan-1-one (2b) (16): The representative procedure was followed, using substrate (E)-3-phenyl-1-(3-(prop-2- yn-1-yloxy)phenyl)prop-2-en-1-one (0.053 g, 0.202 mmol) and the reaction mixture was stirred at room temperature (27oC) for 3 h. Purification by column chromatography on silica gel (petroleum ether/EtOAc: 50/1) yielded 3-Phenyl-1-(3-(prop-2-yn-1- yloxy)phenyl)propan-1-one (0.037 g, 69%) as yellow oil.1H-NMR (400 MHz, CDCl3): δ = 7.57 (d, J = 8.1 Hz, 2H, Ar–H), 7.38 (t, J = 7.9 Hz, 1H, Ar–H), 7.30 (t, J = 7.4 Hz, 2H, Ar–H), 7.26-7.16 (m, 4H, Ar–H), 4.73 (d, J = 2.3 Hz, 2H, CH2), 3.28 (t, J = 7.7 Hz, 2H, CH2), 3.06 (t, J = 7.6 Hz, 2H, CH2), 2.53 (t, J = 2.2 Hz, 1H, CH). 13C{1H}-NMR (100 MHz, CDCl3): δ = 198.9 (CO), 157.9 (Cq), 141.4 (Cq), 138.4 (Cq), 129.8 (CH), 128.7 (2C, CH), 128.6 (2C, CH), 126.3 (CH), 121.6 (CH), 120.4 (CH), 113.7 (CH), 78.2
(Cq), 76.1 (CH), 56.1 (CH2), 40.7 (CH2), 30.3 (CH2). HRMS (ESI): m/z Calcd for C18H16O2 + H+ [M + H]+ 265.1223; Found 265.1217. Example 11: Synthesis of 1-(3-(Oxiran-2-ylmethoxy)phenyl)-3-phenylpropan-1-one (2c) (17): The representative procedure was followed, using substrate (E)-1-(3-(oxiran-2- ylmethoxy)phenyl)-3-phenylprop-2-en-1-one (0.057 g, 0.203 mmol) and the reaction mixture was stirred at room temperature (27 oC) for 4 h. Purification by column chromatography on silica gel (petroleum ether/EtOAc: 30/1) yielded 1-(3-(Oxiran-2- ylmethoxy)phenyl)-3-phenylpropan-1-one (0.039 g, 68%) as yellow oil. 1H-NMR (400 MHz, CDCl3): δ = 7.56 (d, J = 7.8 Hz, 1H, Ar–H), 7.50 (t, J = 1.9 Hz, 1H, Ar–H), 7.36 (t, J = 7.9 Hz, 1H, Ar–H), 7.30 (t, J = 7.3 Hz, 2H, Ar–H), 7.26-7.19 (m, 3H, Ar–H), 7.14 (dd, J = 2.5, 0.6 Hz, 1H, Ar–H), 4.30 (dd, J = 11.0, 2.9 Hz, 1H, CH), 3.97 (dd, J = 11.0, 5.9Hz, 1H, CH), 3.39-3.35 (m, 1H, CH), 3.29 (t, J = 7.6 Hz, 2H, CH2), 3.06 (t, J = 7.6 Hz, 2H, CH2), 2.92 (t, J = 4.5 Hz, 1H, CH2), 2.67 (dd, J = 4.9 Hz, 2.63 Hz, 1H, CH2). 13C{1H}-NMR (100 MHz, CDCl3): δ = 199.1 (CO), 158.9 (Cq), 141.4 (Cq), 138.4 (Cq), 129.9 (CH), 128.7 (2C, CH), 128.6 (2C, CH), 126.3 (CH), 121.4 (CH), 120.3 (CH), 113.2 (CH), 69.1 (CH2), 50.2 (CH), 44.7 (CH2), 40.7 (CH2), 30.3 (CH2). HRMS (ESI): m/z Calcd for C18H18O3 + H+ [M + H]+ 283.1329; Found 283.1223. Example 12: Synthesis of 2-(4-Acetylphenoxy)-1,3-diphenylpropan-1-one (2d) (40): The representative procedure was followed, using substrate (Z)-2-(4-acetylphenoxy)-1,3- diphenylprop-2-en-1-one (0.069 g, 0.202 mmol) and the reaction mixture was stirred at room temperature (27 oC) for 3 h. Purification by column chromatography on silica gel (petroleum ether/EtOAc: 30/1) yielded 2-(4-Acetylphenoxy)-1,3-diphenylpropan-1-one (0.040 g, 57%) as yellow solid. 1H-NMR (500 MHz, CDCl3): δ = 8.04 (d, J = 7.9 Hz, 2H, Ar–H), 7.82 (d, J = 8.8 Hz, 2H, Ar–H), 7.61 (t, J = 7.4 Hz, 1H, Ar–H), 7.48 (t, J = 7.8 Hz, 2H, Ar–H), 7.32-7.23 (m, 5H, Ar–H), 6.84 (d, J = 8.9 Hz, 2H, Ar–H), 5.61 (dd, J = 7.4, 5.3 Hz, 1H, CH), 3.36-3.34 (m, 2H, CH2), 2.48 (s, 3H, CH3). 13C{1H}-NMR (125 MHz, CDCl3): δ = 197.4 (CO), 196.8 (CO), 161.5 (Cq), 136.6 (Cq), 134.4 (Cq), 134.2 (CH), 131.2 (Cq), 130.8 (2C, CH), 129.5 (2C, CH), 129.1 (2C, CH), 128.9 (2C, CH), 128.8 (2C, CH), 127.3 (CH), 115.1 (2C, CH), 81.8 (CH), 39.4 (CH2), 26.5 (CH3). HRMS (ESI): m/z Calcd for C23H20O3 + H+ [M + H]+ 345.1485; Found 345.1478.
ADVANTAGES OF THE INVENTION ^ The present invention provides process of hydrogenation wherein the novel manganese catalyst used for hydrogenation of various substrates such as α,β- unsaturated ketones, aldehydes, and imines (of Formula IIA or IIB). ^ Hydrogenation of various substrates such as α,β-unsaturated ketones , aldehydes, and imines (of Formula IIA or IIB) is carried out at room temperature and low H2 pressure, wherein lower temperature conditions are quite suitable to yield high purified and selectively hydrogenated products. ^ Use of 3rd most abundant transition metal as catalyst. ^ Excellent chemoselectivity in the reduction of C=C, C=O and C=N. ^ Hydrogenation at pressure of 5 bar H2 and room temperature. ^ Use of mild base and atom-efficient H2 source. ^ Provides broad substrates scope with excellent tolerance of hydrogen-sensitive functionalities. ^ Using the sustainable molecular hydrogen and a mild K3PO4 base, the Mn catalyst of formula I hydrogenate diverse unsaturated ketones at room temperature with the compatibility of sensitive functionalities, such as halides (- F, -Cl, -Br, -I), alkoxy, hydroxy, epoxide, acetyl, nitrile, nitro, unconjugated alkenyl and alkynyl groups. ^ Additionally, a wide range of heteroarenes like indole, pyrrole, furan, thiophene, and pyridine derived unsaturated ketones could be chemoselectively hydrogenated to the corresponding saturated ketones. ^ The C=O bond in aldehydes and C=N bond in imines were preferentially hydrogenated over the C=C bond using the Mn catalyst at an extremely mild reaction conditions.
Claims
We Claim: 1. A manganese based catalyst complex of Formula I or its isomeric forms, for hydrogenation of substrate wherein the substrate is select from α, β-unsaturated ketone , aldehyde and imine (of Formula IIA or IIB); the formula I is represented by:
Formula I wherein, Mn is manganese atom or manganese ion in oxidation state (I); wherein R1 is selected from the group consisting of hydrogen, (C1-C4)alkyl, aryl, alkyl aryl, alkoxy, cycloalkyl, alkyl cycloalkyl, and alkylcarboxy; R2 is selected from the group consisting of hydrogen and (C1-C4)alkyl; R3 and R4 are each independently selected from the group consisting of (C1-C4)alkyl, unsubstituted aryl, substituted aryl and cycloalkyl; and X is selected from the group consisting of halide, organosulfonate oxoanion (triflate), boron trifluoride, and tetrafluoroborate; wherein R1 and R2 may be identical or different, and R3 and R4 are the substituents of phosphine moiety. 2. The manganese based catalyst complex of Formula I as claimed in claim 1, wherein said complex is selected from the group consisting of: a) N-(diphenylphosphaneyl)-6-(1H-pyrazol-1-yl)pyridin-2-amine Mn(CO)2Br complex (1a) (Mn-1)
, b) N-(di-iso-propylphosphaneyl)-6-(1H-pyrazol-1-yl)pyridin-2-amine Mn(CO)2Br complex (1b) (Mn-2)
, c) N-(di-tert-butylphosphaneyl)-6-(1H-pyrazol-1-yl)pyridin-2-amine Mn(CO)2Br complex (1c) (Mn-3)
d) N-(di-tert-butylphosphaneyl)-N-methyl-6-(1H-pyrazol-1-yl)pyridin-2-amine Mn(CO)2Br complex (1d) (Mn-4)
. 3. A process of preparation of the manganese based catalyst complex of Formula I as claimed in claim 1, comprising the steps of: a) reacting a ligand compound of formula III with substituted pentacarbonylmanganese [Mn(CO)5X] with a solvent in a container to obtain a reaction mixture
Formula III wherein R1, R2, R3, R4 and X are the same as defined under formula I in claim 1; b) stirring the reaction mixture of step a) under inert atmosphere at a temperature in the range of 27-80 oC for a time period of up to 48 hrs; c) purifying the mixture of step b) to obtain the manganese catalyst of Formula I. 4. The process as claimed in claim 3, wherein the ligand compound of formula III used in step a) is selected from N-(diphenylphosphaneyl)-6-(1H-pyrazol-1-yl)pyridin-2- amine (L1), N-(di-n-propylphosphaneyl)-6-(1H-pyrazol-1-yl)pyridin-2-amine (L2),
N-(di-tert-butylphosphaneyl)-6-(1H-pyrazol-1-yl)pyridin-2-amine (L3) and N-(di- tert-butylphosphaneyl)-N-methyl-6-(1H-pyrazol-1-yl)pyridin-2-amine (L4). 5. The process as claimed in claim 3, the solvent used in step a) is selected from tetrahydrofuran, 2-methyl tetrahydrofuran and toluene. 6. A process for hydrogenation of substrate selected from α, β-unsaturated ketone, aldehyde and imine (of Formula IIA or IIB) by using the manganese based catalyst complex of Formula I as claimed in claim 1, comprising the steps of: (i) preparing a mixture of a substrate of Formula IIA or IIB in the presence of Mn- catalyst of Formula I and a base in dry vial with stir bar
Formula IIA Formula IIB; (ii) transferring the reaction vial of step i) in an autoclave under argon atmosphere; (iii) adding a polar solvent in the vial of step ii) and pressurizing the autoclave with H2 gas followed by venting for five times; (iv) pressurizing the autoclave with H2 gas of pressure ranging between 5-50 bar, and stirring the mixture with a speed of 500-800 rpm at a temperature in the range of 27- 50 ºC for a time period of 1 to 24 hrs to obtain a crude hydrogenated compound; and (v) purifying the crude hydrogenated compound of step iv) to obtain desired hydrogenated compounds of formula IV
Formula IVA Formula IVB Wherein in formula IVA: X is oxo group (O) or nitrogen (NR1) group, where R1 is alkyl or aryl moiety; R is hydrogen, alkyl (C1-C10), (un)substituted aryl, (un)substituted heteroaryl, alkene, alkyne; A and Y is independently selected from hydrogen, alkyl (C1-C10), (un)substituted aryl, (un)substituted heteroaryl, alkene, alkyne, ferrocene, alkoxy, where the substituted aryl
or heteroaryl maybe further substituted with aryl, alkoxy, alkyl, halogen, nitro, cyano, aryl ether, alkyl ether, aryl alkyl ether, CF3, (un)substituted amino, alkyl amino, aryl amino, ferrocene, alkoxy alkyl ether, alkyne alkyl ether, alkylene alkyl ether, hydroxyl, cyclic saturated or unsaturated ring of aryl or heteroaryl with number of rings from 0 to 4; B is selected from hydrogen, alkene, alkyne, alkyl, aryl, heteroaryl, ferrocene, halogen; and A and B optionally together may form saturated or unsaturated ring of aryl or heteroaryl which may further be substituted with hydrogen, alkyl, aryl, heteroaryl, hydroxyl, alkylhydroxyl, alkyl aryl ether, aryl alkyl ether, nitro, cyano, and halogen; in formula IVB: X is oxo group (O) or nitrogen (NR3) group, where R3 is alkyl or aryl moiety; R1 is selected from hydrogen, alkyl (C1-C10), (un)substituted aryl, (un)substituted heteroaryl, alkene, alkyne, ferrocene, alkoxy, where the substituted aryl or heteroaryl maybe further substituted with aryl, alkoxy, alkyl, halogen, nitro, cyano, aryl ether, alkyl ether, aryl alkyl ether, CF3, (un)substituted amino, alkyl amino, aryl amino, ferrocene, alkoxy alkyl ether, alkyne alkyl ether, alkylene alkyl ether, hydroxyl, cyclic saturated or unsaturated ring of aryl or heteroaryl with number of rings from 0 to 4; R2 is selected from hydrogen, alkene, alkyne, alkyl, aryl, heteroaryl, ferrocene, halogen; and R1 and R2 optionally together may form saturated or unsaturated ring of aryl or heteroaryl which may further be substituted with hydrogen, alkyl, aryl, heteroaryl, hydroxyl, alkylhydroxyl, alkyl aryl ether, aryl alkyl ether, nitro, cyano, and halogen. 7. The process as claimed in claim 6, wherein the hydrogenated compounds of formula IVA or IVB are selected from the group consisting of: (i) 1-(3-(Allyloxy)phenyl)-3-phenylpropan-1-one (2a)
, (ii) 3-Phenyl-1-(3-(prop-2-yn-1-yloxy)phenyl)propan-1-one (2b)
,
(iii) 1-(3-(Oxiran-2-ylmethoxy)phenyl)-3-phenylpropan-1-one (2c)
(iv) 2-(4-Acetylphenoxy)-1,3-diphenylpropan-1-one (2d)
. 8. The process as claimed in claim 6, wherein the base is selected from the group consisting of potassium carbonate, potassium phosphate, potassium hydroxide, tripotassium phosphate, potassium tert-butoxide, sodium tert-butoxide, sodium carbonate, cesium carbonate, sodium hydroxide, lithium carbonate, lithium hydroxide, calcium hydroxide, potassium bicarbonate, sodium bicarbonate, sodium methoxide, lithium bicarbonate and tertiary amines. 9. The process as claimed in claim 6, wherein the polar solvent is selected from simple alcohols comprising C1-10 hydrocarbyl alcohol, saturated aliphatic C1-C8 alcohol, polyvalent alcohol; ether based solvent, , or mixtures thereof. 10. The process as claimed in claim 6, wherein the purification of step v) is done by concentrating the crude hydrogenated compound and subjecting it to a column chromatography on silica gel.
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US20120323007A1 (en) * | 2011-06-20 | 2012-12-20 | Kuo-Wei Huang | Phospho-amino pincer-type ligands and catalytic metal complexes thereof |
WO2017137984A1 (en) * | 2016-02-09 | 2017-08-17 | Yeda Research And Development Co. Ltd. | Manganese based complexes and uses thereof for homogeneous catalysis |
WO2020144476A1 (en) * | 2019-01-08 | 2020-07-16 | University Court Of The University Of St Andrews | Manganese catalysts and their use in hydrogenation of ketones |
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US20120323007A1 (en) * | 2011-06-20 | 2012-12-20 | Kuo-Wei Huang | Phospho-amino pincer-type ligands and catalytic metal complexes thereof |
WO2017137984A1 (en) * | 2016-02-09 | 2017-08-17 | Yeda Research And Development Co. Ltd. | Manganese based complexes and uses thereof for homogeneous catalysis |
WO2020144476A1 (en) * | 2019-01-08 | 2020-07-16 | University Court Of The University Of St Andrews | Manganese catalysts and their use in hydrogenation of ketones |
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LI WENXIN, ZHAO JUNYI; ZHANG XUEQUAN; GONG DIRONG: "Capability of PN 3 -type Cobalt Complexes toward Selective (Co-)Polymerization of Myrcene, Butadiene, and Isoprene: Access to Biosourced Polymers", INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH, AMERICAN CHEMICAL SOCIETY, vol. 58, no. 8, 27 February 2019 (2019-02-27), pages 2792 - 2800, XP093173024, ISSN: 0888-5885, DOI: 10.1021/acs.iecr.8b05866 * |
MAGNUS B. WIDEGREN, MATTHEW L. CLARKE: "Towards practical earth abundant reduction catalysis: design of improved catalysts for manganese catalysed hydrogenation", CATALYSIS SCIENCE & TECHNOLOGY, ROYAL SOCIETY OF CHEMISTRY, UK, vol. 9, no. 21, 28 October 2019 (2019-10-28), UK , pages 6047 - 6058, XP055672525, ISSN: 2044-4753, DOI: 10.1039/C9CY01601E * |
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