WO2001004131A1 - Diphosphine ligands for metal complexes - Google Patents
Diphosphine ligands for metal complexes Download PDFInfo
- Publication number
- WO2001004131A1 WO2001004131A1 PCT/EP2000/006658 EP0006658W WO0104131A1 WO 2001004131 A1 WO2001004131 A1 WO 2001004131A1 EP 0006658 W EP0006658 W EP 0006658W WO 0104131 A1 WO0104131 A1 WO 0104131A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- alkyl
- substituted
- phenyl
- unsubstituted
- alkoxy
- Prior art date
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- 239000003446 ligand Substances 0.000 title claims abstract description 39
- VURFVHCLMJOLKN-UHFFFAOYSA-N diphosphane Chemical compound PP VURFVHCLMJOLKN-UHFFFAOYSA-N 0.000 title claims abstract description 37
- 229910052751 metal Inorganic materials 0.000 title claims abstract description 26
- 239000002184 metal Substances 0.000 title claims abstract description 26
- 238000005984 hydrogenation reaction Methods 0.000 claims abstract description 52
- 150000001875 compounds Chemical class 0.000 claims abstract description 38
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims abstract description 8
- -1 dimethylene, trimethylene, tetramethylene, pentamethylene Chemical class 0.000 claims description 55
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
- 229910052739 hydrogen Inorganic materials 0.000 claims description 25
- 239000001257 hydrogen Substances 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 21
- 125000004432 carbon atom Chemical group C* 0.000 claims description 18
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 14
- 150000001450 anions Chemical class 0.000 claims description 14
- XYFCBTPGUUZFHI-UHFFFAOYSA-N phosphine group Chemical group P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 12
- 239000012429 reaction media Substances 0.000 claims description 12
- 239000004215 Carbon black (E152) Substances 0.000 claims description 7
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 229930195733 hydrocarbon Natural products 0.000 claims description 7
- 150000007524 organic acids Chemical class 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 150000007522 mineralic acids Chemical class 0.000 claims description 6
- 229910052700 potassium Inorganic materials 0.000 claims description 6
- 229910052708 sodium Inorganic materials 0.000 claims description 6
- 229910052783 alkali metal Inorganic materials 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 150000001340 alkali metals Chemical class 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- 230000003197 catalytic effect Effects 0.000 claims description 4
- 125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 claims description 4
- 229910052744 lithium Inorganic materials 0.000 claims description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 229910052703 rhodium Inorganic materials 0.000 claims description 4
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 claims description 3
- 229910052741 iridium Inorganic materials 0.000 claims description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
- 125000004849 alkoxymethyl group Chemical group 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 150000001924 cycloalkanes Chemical class 0.000 claims description 2
- 150000001993 dienes Chemical class 0.000 claims description 2
- 125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 claims description 2
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 2
- 239000002638 heterogeneous catalyst Substances 0.000 claims description 2
- 239000002815 homogeneous catalyst Substances 0.000 claims description 2
- 150000004678 hydrides Chemical group 0.000 claims description 2
- 150000004715 keto acids Chemical class 0.000 claims description 2
- 150000005673 monoalkenes Chemical class 0.000 claims description 2
- 229910052701 rubidium Inorganic materials 0.000 claims description 2
- 150000004696 coordination complex Chemical class 0.000 claims 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 2
- 125000002030 1,2-phenylene group Chemical class [H]C1=C([H])C([*:1])=C([*:2])C([H])=C1[H] 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 34
- 239000003054 catalyst Substances 0.000 abstract description 33
- 150000001298 alcohols Chemical class 0.000 abstract description 7
- 125000001424 substituent group Chemical group 0.000 abstract description 4
- 230000003381 solubilizing effect Effects 0.000 abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
- 239000000243 solution Substances 0.000 description 40
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- 239000000203 mixture Substances 0.000 description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 23
- 238000002360 preparation method Methods 0.000 description 22
- 238000006243 chemical reaction Methods 0.000 description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 150000003254 radicals Chemical class 0.000 description 16
- 239000000047 product Substances 0.000 description 15
- 239000012948 isocyanate Substances 0.000 description 14
- 150000002513 isocyanates Chemical class 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- 239000010948 rhodium Substances 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- SJYNFBVQFBRSIB-UHFFFAOYSA-N norbornadiene Chemical compound C1=CC2C=CC1C2 SJYNFBVQFBRSIB-UHFFFAOYSA-N 0.000 description 8
- 239000000758 substrate Substances 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 150000005691 triesters Chemical class 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 150000001735 carboxylic acids Chemical class 0.000 description 6
- 239000007795 chemical reaction product Substances 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000003960 organic solvent Substances 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- XODAOBAZOQSFDS-UHFFFAOYSA-N 2-acetamido-3-phenylprop-2-enoic acid Chemical compound CC(=O)NC(C(O)=O)=CC1=CC=CC=C1 XODAOBAZOQSFDS-UHFFFAOYSA-N 0.000 description 5
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 125000000217 alkyl group Chemical group 0.000 description 5
- 229910052786 argon Inorganic materials 0.000 description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 5
- 230000003287 optical effect Effects 0.000 description 5
- 239000008363 phosphate buffer Substances 0.000 description 5
- 150000003672 ureas Chemical class 0.000 description 5
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 4
- SZNYYWIUQFZLLT-UHFFFAOYSA-N 2-methyl-1-(2-methylpropoxy)propane Chemical compound CC(C)COCC(C)C SZNYYWIUQFZLLT-UHFFFAOYSA-N 0.000 description 4
- OZJPLYNZGCXSJM-UHFFFAOYSA-N 5-valerolactone Chemical compound O=C1CCCCO1 OZJPLYNZGCXSJM-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 4
- 229910000397 disodium phosphate Inorganic materials 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 150000002576 ketones Chemical class 0.000 description 4
- 229940098779 methanesulfonic acid Drugs 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- HHVIBTZHLRERCL-UHFFFAOYSA-N sulfonyldimethane Chemical compound CS(C)(=O)=O HHVIBTZHLRERCL-UHFFFAOYSA-N 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- 238000004679 31P NMR spectroscopy Methods 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- UKLDJPRMSDWDSL-UHFFFAOYSA-L [dibutyl(dodecanoyloxy)stannyl] dodecanoate Chemical compound CCCCCCCCCCCC(=O)O[Sn](CCCC)(CCCC)OC(=O)CCCCCCCCCCC UKLDJPRMSDWDSL-UHFFFAOYSA-L 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 239000012736 aqueous medium Substances 0.000 description 3
- 239000012431 aqueous reaction media Substances 0.000 description 3
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 3
- 239000004327 boric acid Substances 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 3
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 239000012975 dibutyltin dilaurate Substances 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 150000002170 ethers Chemical class 0.000 description 3
- 125000004494 ethyl ester group Chemical group 0.000 description 3
- 229960000304 folic acid Drugs 0.000 description 3
- 235000019152 folic acid Nutrition 0.000 description 3
- 239000011724 folic acid Substances 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 150000008282 halocarbons Chemical class 0.000 description 3
- 150000002367 halogens Chemical group 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 150000002596 lactones Chemical class 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N monoethanolamine hydrochloride Natural products NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical class C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 2
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 2
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 235000019502 Orange oil Nutrition 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 229910000831 Steel Inorganic materials 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 150000001336 alkenes Chemical class 0.000 description 2
- IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- SWIRFWUEJODNRG-LTCKWSDVSA-L disodium;(2s)-2-[[4-[(2-amino-4-oxo-1h-pteridin-6-yl)methylamino]benzoyl]amino]pentanedioate Chemical compound [Na+].[Na+].C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC([O-])=O)C([O-])=O)C=C1 SWIRFWUEJODNRG-LTCKWSDVSA-L 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 150000004658 ketimines Chemical class 0.000 description 2
- 150000003951 lactams Chemical class 0.000 description 2
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 150000002739 metals Chemical class 0.000 description 2
- USKHBABPFFAKJD-UHFFFAOYSA-N methyl 2-acetamido-3-phenylprop-2-enoate Chemical compound COC(=O)C(NC(C)=O)=CC1=CC=CC=C1 USKHBABPFFAKJD-UHFFFAOYSA-N 0.000 description 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 2
- 239000003607 modifier Substances 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000010502 orange oil Substances 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- RVROFNKKFDIHBM-UHFFFAOYSA-N phosphane;pyrrolidine Chemical class P.P.C1CCNC1 RVROFNKKFDIHBM-UHFFFAOYSA-N 0.000 description 2
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 150000003283 rhodium Chemical class 0.000 description 2
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 2
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 2
- 239000010959 steel Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 2
- 150000003457 sulfones Chemical class 0.000 description 2
- 150000003462 sulfoxides Chemical class 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 125000000383 tetramethylene group Chemical class [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 2
- ARCGXLSVLAOJQL-UHFFFAOYSA-N trimellitic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)C(C(O)=O)=C1 ARCGXLSVLAOJQL-UHFFFAOYSA-N 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- MAUMSNABMVEOGP-UHFFFAOYSA-N (methyl-$l^{2}-azanyl)methane Chemical group C[N]C MAUMSNABMVEOGP-UHFFFAOYSA-N 0.000 description 1
- PRBHEGAFLDMLAL-UHFFFAOYSA-N 1,5-Hexadiene Natural products CC=CCC=C PRBHEGAFLDMLAL-UHFFFAOYSA-N 0.000 description 1
- VYXHVRARDIDEHS-UHFFFAOYSA-N 1,5-cyclooctadiene Chemical group C1CC=CCCC=C1 VYXHVRARDIDEHS-UHFFFAOYSA-N 0.000 description 1
- 239000004912 1,5-cyclooctadiene Chemical group 0.000 description 1
- QYEMLLMAPAWTPT-UHFFFAOYSA-N 1h-imidazol-2-ylurea Chemical compound NC(=O)NC1=NC=CN1 QYEMLLMAPAWTPT-UHFFFAOYSA-N 0.000 description 1
- SBASXUCJHJRPEV-UHFFFAOYSA-N 2-(2-methoxyethoxy)ethanol Chemical compound COCCOCCO SBASXUCJHJRPEV-UHFFFAOYSA-N 0.000 description 1
- VKJCJJYNVIYVQR-UHFFFAOYSA-N 2-(3-bromopropyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCCBr)C(=O)C2=C1 VKJCJJYNVIYVQR-UHFFFAOYSA-N 0.000 description 1
- FBRJYBGLCHWYOE-UHFFFAOYSA-N 2-(trifluoromethyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C(F)(F)F FBRJYBGLCHWYOE-UHFFFAOYSA-N 0.000 description 1
- ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 1
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 241001061225 Arcos Species 0.000 description 1
- 229910017048 AsF6 Inorganic materials 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- KSSJBGNOJJETTC-UHFFFAOYSA-N COC1=C(C=CC=C1)N(C1=CC=2C3(C4=CC(=CC=C4C=2C=C1)N(C1=CC=C(C=C1)OC)C1=C(C=CC=C1)OC)C1=CC(=CC=C1C=1C=CC(=CC=13)N(C1=CC=C(C=C1)OC)C1=C(C=CC=C1)OC)N(C1=CC=C(C=C1)OC)C1=C(C=CC=C1)OC)C1=CC=C(C=C1)OC Chemical compound COC1=C(C=CC=C1)N(C1=CC=2C3(C4=CC(=CC=C4C=2C=C1)N(C1=CC=C(C=C1)OC)C1=C(C=CC=C1)OC)C1=CC(=CC=C1C=1C=CC(=CC=13)N(C1=CC=C(C=C1)OC)C1=C(C=CC=C1)OC)N(C1=CC=C(C=C1)OC)C1=C(C=CC=C1)OC)C1=CC=C(C=C1)OC KSSJBGNOJJETTC-UHFFFAOYSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical group NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- NMCHAKBEEGFTSD-UHFFFAOYSA-N Cc1ccc(P(c2ccccc2)c2ccccc2)c(c1)-c1cc(CO)ccc1P(c1ccccc1)c1ccccc1 Chemical group Cc1ccc(P(c2ccccc2)c2ccccc2)c(c1)-c1cc(CO)ccc1P(c1ccccc1)c1ccccc1 NMCHAKBEEGFTSD-UHFFFAOYSA-N 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 241000648097 Genetta pardina Species 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
- 229910004039 HBF4 Inorganic materials 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- QLZHNIAADXEJJP-UHFFFAOYSA-N Phenylphosphonic acid Chemical compound OP(O)(=O)C1=CC=CC=C1 QLZHNIAADXEJJP-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- PQHKXSOICTYGQD-OUTSHDOLSA-N [(3s,5s)-5-(diphenylphosphanylmethyl)pyrrolidin-3-yl]-diphenylphosphane Chemical compound C=1C=CC=CC=1P([C@H]1C[C@H](NC1)CP(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 PQHKXSOICTYGQD-OUTSHDOLSA-N 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 150000008107 benzenesulfonic acids Chemical class 0.000 description 1
- GRSTVVGJSKHCCS-UHFFFAOYSA-N bis(1h-imidazol-2-yl)methanone Chemical compound N=1C=CNC=1C(=O)C1=NC=CN1 GRSTVVGJSKHCCS-UHFFFAOYSA-N 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- CDQSJQSWAWPGKG-UHFFFAOYSA-N butane-1,1-diol Chemical compound CCCC(O)O CDQSJQSWAWPGKG-UHFFFAOYSA-N 0.000 description 1
- ZPFKRQXYKULZKP-UHFFFAOYSA-N butylidene Chemical group [CH2+]CC[CH-] ZPFKRQXYKULZKP-UHFFFAOYSA-N 0.000 description 1
- 235000013877 carbamide Nutrition 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- FOCAUTSVDIKZOP-UHFFFAOYSA-M chloroacetate Chemical compound [O-]C(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-M 0.000 description 1
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 1
- 229940106681 chloroacetic acid Drugs 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- QYQADNCHXSEGJT-UHFFFAOYSA-N cyclohexane-1,1-dicarboxylate;hydron Chemical class OC(=O)C1(C(O)=O)CCCCC1 QYQADNCHXSEGJT-UHFFFAOYSA-N 0.000 description 1
- PDXRQENMIVHKPI-UHFFFAOYSA-N cyclohexane-1,1-diol Chemical compound OC1(O)CCCCC1 PDXRQENMIVHKPI-UHFFFAOYSA-N 0.000 description 1
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- IIXOVPGRABFCAI-UHFFFAOYSA-N cyclohexylmethanediol Chemical compound OC(O)C1CCCCC1 IIXOVPGRABFCAI-UHFFFAOYSA-N 0.000 description 1
- VSSAZBXXNIABDN-UHFFFAOYSA-N cyclohexylmethanol Chemical compound OCC1CCCCC1 VSSAZBXXNIABDN-UHFFFAOYSA-N 0.000 description 1
- 229940120124 dichloroacetate Drugs 0.000 description 1
- JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 1
- XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 description 1
- 229940075557 diethylene glycol monoethyl ether Drugs 0.000 description 1
- PBWZKZYHONABLN-UHFFFAOYSA-M difluoroacetate Chemical compound [O-]C(=O)C(F)F PBWZKZYHONABLN-UHFFFAOYSA-M 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- 125000005805 dimethoxy phenyl group Chemical group 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- QEWYKACRFQMRMB-UHFFFAOYSA-N fluoroacetic acid Chemical compound OC(=O)CF QEWYKACRFQMRMB-UHFFFAOYSA-N 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- PYGSKMBEVAICCR-UHFFFAOYSA-N hexa-1,5-diene Chemical group C=CCCC=C PYGSKMBEVAICCR-UHFFFAOYSA-N 0.000 description 1
- 125000004051 hexyl group Chemical class [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000007172 homogeneous catalysis Methods 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- GBHRVZIGDIUCJB-UHFFFAOYSA-N hydrogenphosphite Chemical compound OP([O-])[O-] GBHRVZIGDIUCJB-UHFFFAOYSA-N 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 1
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 229910001507 metal halide Inorganic materials 0.000 description 1
- 150000005309 metal halides Chemical class 0.000 description 1
- 125000006178 methyl benzyl group Chemical group 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- UICCSKORMGVRCB-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-n',n'-diethylethane-1,2-diamine Chemical compound CCN(CC)CCNCCN(CC)CC UICCSKORMGVRCB-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052756 noble gas Inorganic materials 0.000 description 1
- 150000002835 noble gases Chemical class 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- ZFLIKDUSUDBGCD-UHFFFAOYSA-N parabanic acid Chemical compound O=C1NC(=O)C(=O)N1 ZFLIKDUSUDBGCD-UHFFFAOYSA-N 0.000 description 1
- 125000001147 pentyl group Chemical class C(CCCC)* 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- JXOWIQSNDGMEJD-UHFFFAOYSA-N phenyl-(4-phenylphosphanylpyrrolidin-3-yl)phosphane Chemical compound C=1C=CC=CC=1PC1CNCC1PC1=CC=CC=C1 JXOWIQSNDGMEJD-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003009 phosphonic acids Chemical class 0.000 description 1
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
- 125000004437 phosphorous atom Chemical group 0.000 description 1
- 150000003022 phthalic acids Chemical class 0.000 description 1
- 125000005543 phthalimide group Chemical class 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- ULWHHBHJGPPBCO-UHFFFAOYSA-N propane-1,1-diol Chemical compound CCC(O)O ULWHHBHJGPPBCO-UHFFFAOYSA-N 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 150000003303 ruthenium Chemical class 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000011949 solid catalyst Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 150000003504 terephthalic acids Chemical class 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 229940066528 trichloroacetate Drugs 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical class OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 125000005023 xylyl group Chemical group 0.000 description 1
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
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/50—Organo-phosphines
- C07F9/5027—Polyphosphines
-
- 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
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0073—Rhodium compounds
- C07F15/008—Rhodium compounds without a metal-carbon linkage
-
- 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
- C07F17/00—Metallocenes
- C07F17/02—Metallocenes of metals of Groups 8, 9 or 10 of the Periodic System
-
- 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
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/572—Five-membered rings
Definitions
- the invention relates to ditertiary diphosphine ligands for metal complexes as hydrogenation catalysts which are soluble in a polar reaction medium, for example water and organic solvents such as methanol, due to solubilizing groups and which can easily be separated from the reaction mixture after the hydrogenation, possibly by changing the pH.
- a polar reaction medium for example water and organic solvents such as methanol
- Hydrogenation processes which may be enantioselective or diastereoselective, using metal complexes of, for example, rhodium, iridium or ruthenium and achiral or chiral ditertiary diphosphine ligands have become important processes for the synthesis of intermediates or active substances such as pesticides and pharmaceuticals.
- aqueous or polar reaction media are often the medium of choice because of the solubility of starting compounds, but this then also requires water-soluble hydrogenation catalysts which can easily be separated from the reaction product by extraction.
- EP-A-0 329 043 describes pyrrolidine diphosphines bound to polyethylene glycol via a diisocyanate bridge; the rhodium complexes of these are used for the hydrogenation of 2,3-dehydrophosphinothricin - ⁇ - derivatives in aqueous solution.
- the stoichiometric composition of the complexes is difficult to control, so that reproducibility is not always ensured.
- Pyrrolidine diphosphines bound to a polyacrylic acid suffer from the same problem: although their complexes are water-soluble, the loading with the diphosphine is not sufficiently controllable [T. Malmstr ⁇ m et al., J. of Mol. Cat. A: Chemical 139, pages 259-270 (1999)].
- the enantioselectivity depends on the loading with the diphosphine and the catalyst activity is relatively low.
- ligands for hydrogenation catalysts which are soluble in a polar reaction medium, have a good catalyst activity, enable high optical yields to be achieved when the hydrogenation catalysts are chiral, can be used in the acidic to basic range of an aqueous reaction medium to set optimized reaction conditions, can be used in polar solvents such as alcohols, have a high catalyst activity even at high ratios of substrate to catalyst, for example above 100, lead to high optical yields and can easily be separated from the reaction mixture.
- the invention provides, firstly, compounds of the formulae I and la, A-[[Si-(C 1 -C 4 alkyl) 2 ] x -C m H 2m -Xi-C(0)-X 1 '- C n H 2n -Y ! -(R-Y) y ] r (I),
- A is a monovalent to tetravalent framework of a ditertiary diphosphine bound via a C atom
- Ai is a monovalent framework of a 3-8-membered N- heterocyclic ditertiary diphosphine bound via the N atom
- Xi is -0-, -NH- or -N- (C ⁇ -Calkyl) -,
- Xi' is -NH- or -N- (C ⁇ -C 4 alkyl)-; or X 1 ' is -O- when Xi is -NH- or -N-(C ⁇ -C 4 alkyl)-,
- Y is -C0 2 M, -N(C ⁇ -C 4 alkyl) 2 -, -N(C ⁇ -C alkyl) 2 H + X 2 " or -N(C ⁇ -C 4 alkyl) 3 + X 2 " ,
- x is 1 and m is from 2 to 4, or x is 0, m is 0 or an integer from 1 to 4, n is 0 or an integer from 1 to 4, r is an integer from 1 to 4, y is an integer from 1 to 5,
- M is H, an alkali metal or a monovalent hydrocarbon radical having from 1 to 18 C atoms, and
- X 2 is the anion of an inorganic or organic acid.
- the ditertiary diphosphines can be ones in which the phosphine groups are bound (a) to various C atoms of a chain having from 2 to 6 C atoms, preferably a carbon chain having from 2 to 4 C atoms, or (b) directly or via a bridging group of the formula -CR a Rb- either in the ortho positions of a cyclopentadienyl ring or each to a cyclopentadienyl ring of a ferrocenyl group, where R a and R b are identical or different and are H, Ci- C 8 alkyl, C ⁇ -C 4 fluoroalkyl, C 5 -C 6 cycloalkyl, phenyl, benzyl, or phenyl or benzyl substituted by from 1 to 3 C ⁇ -Calkyl or C ⁇ -C 4 alkoxy groups.
- R b is preferably hydrogen.
- R a is preferably hydrogen or C ⁇ -C 4 alkyl.
- the individual phosphine groups may contain identical or different hydrocarbon radicals.
- the individual phosphine groups preferably contain two identical hydrocarbon radicals, with various phosphine groups of this type being able to be bound to the framework of the diphosphine.
- the hydrocarbon radicals can be unsubstituted or substituted and contain from 1 to 20, preferably from 1 to 12, C atoms.
- the individual phosphine groups contain two identical or different radicals selected from the group consisting of linear or branched C ⁇ -C ⁇ alkyl; unsubstituted or C ⁇ -C 6 alkyl- or C ⁇ -C 6 alkoxy- substituted C 5 -C ⁇ 2 cycloalkyl or C 5 -C ⁇ 2 cycloalkyl-CH 2 -; phenyl and benzyl; and phenyl or benzyl substituted by halogen (for example F , CI and Br ) , C ⁇ -C 6 alkyl , Ci-Cehaloalkyl ( for example trif luoromethyl ) , Ci- C 6 alkoxy , C ⁇ -C 6 haloalkoxy ( for example trifluoro- methoxy ) , ( C 6 H 5 ) 3 Si , ( d-C ⁇ 2 alkyl ) 3 Si or
- the two radicals in the phosphine groups can also together be unsubstituted or halogen- , C ⁇ -C 6 alkyl- or C ⁇ -C 6 alkoxy-substituted dimethylene , trimethylene , tetramethylene , pentamethylene or 3 -oxapentane-l , 5- diyl .
- the substituents are preferably bound in the two ortho positions relative to the P atom .
- the phosphine groups can also be groups of the formulae
- o and p are, independently of one another, an integer from 2 to 10, and the sum of o+p is from 4 to 12 and preferably from 5 to 8.
- Examples are [3.3.1]- and [4.2.1] -phobyl of the formulae
- alkyl substituents preferably containing from 1 to 6 C atoms
- alkyl substituents preferably containing from 1 to 6 C atoms
- P alkyl substituents, preferably containing from 1 to 6 C atoms, on P are methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl and the isomers of pentyl and hexyl.
- Examples of unsubstituted or alkyl- substituted cycloalkyl substituents on P are cyclopentyl, cyclohexyl, methylcyclohexyl and ethylcyclohexyl and dimethylcyclohexyl.
- alkyl-, alkoxy-, haloalkyl- and haloalkoxy-substituted phenyl and benzyl substituents on P are methylphenyl, dimethylphenyl, trimethylphenyl, ethylphenyl, methylbenzyl, methoxyphenyl, dimethoxyphenyl, trifluoro ethylphenyl, bistrifluoromethylphenyl, tristrifluoromethylphenyl, trifluoromethoxyphenyl and bistrifluoromethoxyphenyl .
- Preferred phosphine groups are those containing identical or different, preferably identical, radicals selected from the group consisting of C ⁇ -C 6 alkyl, unsubstituted or C ⁇ -C 4 alkyl- or C ⁇ -C 4 alkoxy- monosubstituted to -trisubstituted cyclobutyl, cyclopentyl or cyclohexyl, benzyl and particularly phenyl which is unsubstituted or substituted by from 1 to 3 C ⁇ -C 4 alkyl, C ⁇ -Calkoxy, F, CI, C ⁇ -C 4 fluoroalkyl or C ⁇ -C 4 fluoroalkoxy substituents.
- diphosphine radicals A and Ai in the formulae I and la preferably correspond to the formulae II, Ila and lib,
- Ri , R 2 , R 4 and R 5 are each, independently of one another, a hydrocarbon radical having from 1 to 20 C atoms which is unsubstituted or substituted by halogen, C ⁇ -C 6 alkyl , Ci-Cehaloalkyl , C ⁇ -C 6 alkoxy, C ⁇ -C 6 haloalkoxy, ( C 6 H 5 ) 3 Si , (C ⁇ -C ⁇ 2 alkyl) 3 Si or -C0 2 -Ci-C 6 alkyl ; or R x and R 2 or R 4 and R 5 are in each case together unsubstituted or halogen- , C ⁇ -C 6 alkyl- or C ⁇ -C 6 alkoxy-substituted tetramethylene, pen tame thy lene or 3 -oxapentane-l , 5-diyl ; and R 3 is unsubstituted or C ⁇ -C 6 alkyl- , C
- R 8 is hydrogen, C ⁇ -C 8 alkyl, C ⁇ -C 4 fluoroalkyl, unsubstituted phenyl or phenyl substituted by from 1 to 3 F, CI, Br, C ⁇ -Calkyl, C ⁇ -C 4 alkoxy or fluoromethyl substituents;
- q in formula Ila is 0 or an integer from 1 to 6, where the radical of the formula Ila is unfused or fused with cycloaliphatic, heterocycloaliphatic, aromatic or heteroaromatic radicals, and the radical of the formula Ila is unsubstituted or substituted by halogen, C ⁇ -C 6 alkyl, C ⁇ -C 6 haloalkyl, C ⁇ -C 6 alkoxy, C ⁇ -C 6 haloalkoxy, (C 6 H 5 ) 3 Si, (C ⁇ -C ⁇ 2 alkyl) 3 Si or -C0 2 -Ci-C 6 alkyl; and R 9 and Rio are, independently of one another, C
- R 9 and Rio are preferably methylene, ethylene or linear or branched propylene or butylene .
- the chain formed by R 9 , Rio and N preferably contains from 3 to 5 atoms.
- Ri, R 2 , R and R 5 are preferably identical or different, in particular identical, radicals selected from the group consisting of branched C 3 -C 6 alkyl, unsubstituted or C ⁇ -C 4 alkyl- or C ⁇ -C 4 alkoxy-monosubstituted to -trisubstituted cyclopentyl or cyclohexyl, unsubstituted or C ⁇ -C 4 alkyl- or C ⁇ -C 4 alkoxy- monosubstituted to -trisubstituted benzyl and in particular unsubstituted or C ⁇ -C 4 alkyl-, C ⁇ -C 4 alkoxy-, NH 2 -, OH-, F-, C1-, C ⁇ -C 4 fluoroalkyl- or C ⁇ -C 4 fluoro- alkoxy-monosubstituted to -trisubstituted phenyl.
- R is preferably C ⁇ -C 8 alkyl and particularly preferably C ⁇ -C 6 alkyl which may be interrupted by from one to three -0- or -N(C ⁇ -C 4 alkyl) - groups .
- the alkyl in the group N(C ⁇ -C 4 alkyl) 2 is preferably linear and can be methyl, ethyl, n-propyl or n-butyl .
- Y is particularly preferably -C0 2 M, -N(CH 3 ) 2 -, -N(CH 3 ) 2 H + X 2 " or -N(CH 3 ) 3 + X 2 ⁇ in which M is H, Li, Na, K or C ⁇ -C 4 alkyl, and X 2 is the anion of an inorganic or organic acid.
- M is H, Li, Na, K or C ⁇ -C 4 alkyl
- X 2 is the anion of an inorganic or organic acid.
- m is preferably 0, 1 or 2 and n is preferably 0, 1 or 2.
- r is preferably from 1 to 3, particularly preferably 1 or 2 and very particularly preferably 1.
- y is preferably from 1 to 4, particularly preferably from 1 to 3 and very particularly preferably 1 or 2.
- a cycloalkane radical Y 2 is preferably a 5- or 6-membered cycloalkane radical.
- the alkyl is preferably methyl .
- alkali metals M preference is given to Li, Na or K.
- Anions X 2 derived from an inorganic acid may be, for example, halides such as chloride, bromide and iodide, sulfite, sulfate, hydrogensulfate, carbonate, hydrogen- carbonate, nitrate, phosphite, hydrogenphosphite, phosphate, hydrogenphosphate, tetrafluoroborate or hexafluorophosphate.
- halides such as chloride, bromide and iodide, sulfite, sulfate, hydrogensulfate, carbonate, hydrogen- carbonate, nitrate, phosphite, hydrogenphosphite, phosphate, hydrogenphosphate, tetrafluoroborate or hexafluorophosphate.
- Anions X 2 derived from organic acids are the anions of carboxylic acids, sulfonic acids and phosphonic acids which may contain from 1 to 18, preferably from 1 to 12 and particularly preferably from 1 to 8, C atoms.
- Some preferred examples of anions of organic acids are acetate, propionate, butyrate, monochloroacetate, dichloroacetate and trichloroacetate, monofluoro- acetate, difluoroacetate and trifluoroacetate, hydroxyacetate, oxalate, malonate, and also the anions of cyclohexanemonocarboxylic and cyclohexane- dicarboxylic acids, benzoic acid, phthalic and terephthalic acids, trifluoromethylbenzoic acid, phenylacetic acid, phenylphosphonic acid, methyl- sulfonic, ethylsulfonic, propylsulfonic, butylsulfonic, cyclo
- the group - [Si- (C ⁇ -C 4 alkyl) 2 ] x -C m H 2m -X ⁇ - in the radicals of the formula I is preferably -Si (CH 3 ) 2 -CH 2 CH 2 CH 2 -NH- or -Si(CH 3 ) 2 -CH 2 CH 2 CH 2 -0-.
- Some specific embodiments of the group -CmH ⁇ - are methylene, ethylene, 1,2- or 1, 3-propylene, 1,2-, 1,3-, 1,4- or 2,3-butylene, ethylidene, propylidene and butylidene.
- Some specific embodiments of the group -X ⁇ -C(O) -X x ' - C n H 2n -Y ⁇ - (R-Y)y in the radicals of the formula I are, for example, -NH-C(O) -NH-C (CH 2 -C0 2 H) 3 , -NH-C (O) -NH-CH(CH 2 - C0 2 H) 2 , -NH-C(0)-NH-CH 2 (CH 2 -C0 2 H) , -NH-C (O) -NH-CH 2 -C (CH 2 - C0 2 H) 3 , -NH-C(0)-NH-CH 2 -CH(CH 2 -C0 2 H) 2 -NH-C (0) -NH-CH 2 - CH 2 (CH 2 -C0 2 H) , -0-C(0)-NH-C(CH 2 -C0 2 H) 3 , -O-C (O) -NH-CH(CH 2 -
- NHC 6 H 8 (N(CH 3 ) 2 ) 3 , -0-C(0)-NHC 6 H 9 (N(CH 3 ) 2 ) 2/ -O-C (O) -NHC 6 H 8 - (N(CH 3 ) 2 ) 3 .
- a (CH 3 ) 2 N group can be replaced by a (C 2 H 5 ) 2 N group.
- Particularly preferred groups are -NH-C (O) -NH-C (CH 2 -0- CH 2 CH 2 C0 2 H) 3 , -O-C (O) -NH-C (CH 2 -0-CH 2 CH 2 C0 2 H) 3 , -NH-C(O)- NH-CH 2 CH 2 -N[CH 2 CH 2 -N(CH 3 ) 2 ] 2 , -NH-C (O) -NH-CH 2 -NH-CH 2 CH 2 - N[CH 2 CH 2 -N(CH 3 ) 2 ] 2 and -NH-C (O) -N[CH 2 CH 2 -N(CH 3 ) 2 ] 2 , where the N(CH 3 ) 2 group can be replaced by an N(C 2 H 5 ) 2 group.
- Some specific embodiments of the group -C (0) -Xi' -C n H 2n - Yi-(R-Y) y are ones as listed above but in which -NH- or -0- is left off at the beginning.
- Particularly preferred groups are -C(O) -NH-C (CH 2 -0-CH 2 CH 2 C0 2 H) 3 , -C (0) -NH-CH 2 C (CH 2 -0-CH 2 CH 2 C0 2 H) 3 , -C (O) -NH-CH 2 CH 2 -N[CH 2 CH 2 - N(CH 3 ) 2 ] 2 and -C (O) -NH-CH 2 CH 2 CH 2 -N[CH 2 CH 2 -N(CH 3 ) 2 ] 2 , where the N(CH 3 ) 2 group can be replaced by an N(C 2 H 5 ) 2 group.
- a preferred subgroup of tertiary diphosphines of the formulae I and la consists of those of the formulae
- Rii and R i2 are, independently of one another, linear or branched C ⁇ -C 4 alkylene, and the chain -P-Rn-N-R ⁇ 2 -P- has from 5 to 8 atoms,
- R13 and R i are identical or different groups selected from among unsubstituted or C ⁇ -Calkyl-, C ⁇ -C 4 alkoxy- or trifluoromethyl-substituted C 5 cycloalkyl or C 6 cycloalkyl and unsubstituted or C ⁇ -C 4 alkyl-, C ⁇ -Calkoxy-, F-, Cl- or trifluoromethyl-substituted phenyl,
- R15 and R ⁇ 6 are together C 2 -C 6 alkylene
- R i are, independently of one another, a bond or methylene or ethylidene
- L is a radical of the formula -C(O) -Xi' -C n H 2n -Y ! - (R-Y) y and
- Li is a radical of the formula - [ [Si- (CH 3 ) 2 ] x -C m H 2m -X ⁇ -
- Xi' is -NH- or -N- (C ⁇ -C 4 alkyl) -; or Xi ' is -0- when X x is
- Y is -C0 2 M, -N(CH 3 ) 2 , -N(CH 3 ) 2 H + X 2 " or -N(CH 3 ) 3 + X 2 " , x is 1 and m is 2 or 3 , or x is 0, m is 0 or from 2 to 4, n is 0 or from 2 to 4, r is 1 or 2, y is an integer from 1 to 3 , M is H, Li, Na, K or Ci-C 4 alkyl, and
- X 2 is the anion of an inorganic or organic acid.
- X 2 can be, for example, an anion selected from the group consisting of chloride, bromide, iodide, hydrogensulfate, dihydrogenphosphate, acetate, benzoate, tosylate and methylsulfonate.
- the compounds of the formulae I and la can be prepared in a manner known per se by reacting OH- or NH- functional ditertiary disphosphines with isocyanates or capped isocyanates of a solubilized compound.
- the invention further provides a process for preparing compounds of the formulae I and la, in which a) OH- or NH-functional ditertiary diphosphines of the formulae III and Ilia,
- esters for example methyl or ethyl esters
- carboxylic acids Y is -C0 2 H
- Activated urea derivatives are also referred to as capped isocyanates. These can, for example, correspond to the formula IVa,
- Y, Y x , R, n, y and r are as defined above and R19 is the N-bonded radical of an activating amine.
- Such amines are essentially cyclic secondary amines, preferably N-heteroaromatics such as pyrrole and in particular imidazole.
- the compounds of the formulae IV and IVa are obtainable by reaction of appropriate ureas, for example carbonylbisimidazole, with compounds of the formula H 2 N-C n H 2n -Y ⁇ - (R-Y) y ] r •
- mixtures of isocyanates and capped isocyanates in chemical equilibrium can be formed and can likewise be used.
- the reaction is generally carried out at room temperature or slightly elevated temperature in an inert solvent such as toluene.
- the reaction products can be used directly in further reactions without isolating the isocyanates/capped isocyanates. Syntheses using azolidene are described by H. A. Staab in Angew. Chem. 12, 1962, pages 407 to 419.
- the reaction of functional ditertiary diphosphine and isocyanate/capped isocyanate or vice versa is generally carried out in an inert solvent.
- suitable solvents are aliphatic, cycloaliphatic or aromatic hydrocarbons, halogenated hydrocarbons, ethers, carboxylic esters, lactones, N-substituted carboxamides, lactams and ketones.
- the reaction can be carried out at temperatures of from -20 °C to 100 °C.
- the compounds of the formulae I and la are very useful ligands for metal complexes, in particular ones which can be used as hydrogenation catalysts and are soluble in polar reaction media such as water or aprotic or protic and polar organic solvents, e.g. alcohols, and can be separated off after the hydrogenation, for example by means of extraction, if appropriate after hydrolysis of ester groups and/or changing the pH.
- polar reaction media such as water or aprotic or protic and polar organic solvents, e.g. alcohols
- the invention further provides metal complexes of d 8 metals with compounds of the formulae I and la, in particular metal complexes of the formulae V, Va and Vb
- a 3 is a compound of the formula I or la;
- X is two monoolefin ligands or one diene ligand;
- Me is a d 8 metal selected from the group consisting of Ir and Rh;
- D is -CI, -Br or -I;
- E is the anion of an oxo acid or complex acid;
- X 3 and X 4 are identical or different and are as defined for D or E, or X 3 and X 4 are allyl or 2-methallyl, or X 3 is as defined for D or E and X 4 is hydride.
- D is -Cl, -Br or -I.
- E " is C10 " , CF 3 S0 3 " , CH 3 S0 3 “ , HS0 4 “ , BF 4 " , B (phenyl) 4 “ , PF 6 “ , SbCl 6 “ , AsF 6 “ or SbF 6 " .
- the metal complexes of the formulae V, Va and Vb are prepared by methods known from the literature.
- the metal complexes of the invention are very useful as catalysts for the hydrogenation of organic double and triple bonds .
- the metal complexes of the invention are useful for the enantioselective hydrogenation of compounds containing prochiral carbon-carbon and carbon-heteroatom double bonds. Examples of such compounds are prochiral alkenes, imines and ketones.
- a further aspect of the invention is therefore the use of the novel metal complexes of d 8 metals as heterogeneous or homogeneous catalysts for hydrogenation, preferably for the asymmetric hydrogenation of prochiral compounds having carbon- carbon or carbon-heteroatom double bonds in a polar reaction medium.
- the metal complexes are preferably used for the asymmetric hydrogenation of prochiral compounds having carbon-carbon or carbon-heteroatom double bonds, in particular the Ir complexes for the hydrogenation of prochiral ketimines and the Rh complexes for the hydrogenation of prochiral ketimines and prochiral alkenes .
- the invention further provides a process for the hydrogenation of compounds having carbon-carbon or carbon-heteroatom double bonds, which comprises reacting the compounds at a temperature of from -20 to 150 °C with hydrogen in the presence of catalytic amounts of one or more metal complexes of the invention in a polar reaction medium.
- the metal complexes of the invention are hydrogenation catalysts or precursors of such catalysts which are activated under the hydrogenation conditions.
- the metal complexes can be prepared in situ and used as hydrogenation catalysts.
- the hydrogenations are advantageously carried out under protective gas such as noble gases (argon) .
- the process can be carried out under a hydrogen pressure of from 1 to 500 bar, preferably 1-150 bar, particularly preferably from 1 to 120 bar and in particular from 1 to 100 bar.
- the reaction temperature can be, for example, from 0 to 150 °C, preferably from 10 to 120 °C and particularly preferably from 30 to 100 °C.
- the amount of catalyst depends mainly on the desired reaction time and on economic considerations. Higher amounts of catalyst essentially promote shorter reaction times. Catalysts are preferably used in amounts of from 0.0001 to 10 mol%, particularly preferably from 0.001 to 10 mol% and in particular from 0.01 to 5 mol%, based on the compound to be hydrogenated.
- the molar ratio of substrate to catalyst can be, for example, from 30 to 100000, preferably from 50 to 50000, particularly preferably from 50 to 30000 and in particular from 100 to 2000.
- a particularly advantageous aspect is that the hydrogenation can be carried out in polar reaction media, for example polar organic or aqueous media, and in the acid, neutral or basic range, so that reaction conditions optimized for a particular substrate can be set and the catalysts can easily be separated off, for example by means of extraction. If Y in the formulae I and la is an ester group, this can be hydrolyzed beforehand to form the acid group.
- polar reaction media for example polar organic or aqueous media
- acid, neutral or basic range so that reaction conditions optimized for a particular substrate can be set and the catalysts can easily be separated off, for example by means of extraction. If Y in the formulae I and la is an ester group, this can be hydrolyzed beforehand to form the acid group.
- an aqueous reaction medium is one consisting of only water or water in admixture with a water-miscible or water-immiscible organic solvent.
- the proportion of water is preferably at least 30 per cent by volume, particularly preferably at least 50 per cent by volume and in particular at least 70 per cent by volume.
- the reaction medium very particularly preferably contains only water.
- suitable solvents are alcohols such as methanol, ethanol, propanol, butanol, ethylene glycol and ethylene glycol monomethyl ether; ethers such as diethyl ether, diisobutyl ether, tetrahydrofuran and dioxane; esters and lactones such as ethyl acetate, methyl acetate and valerolactone; sulfoxides and sulfones such as dimethyl sulfoxide, dimethyl sulfone, tetramethylene sulfone; ketones such as acetone or methyl isobutyl ketone; halogenated hydrocarbons such as methylene chloride, chloroform, tetrachloroethane and chlorobenzene; and N-substituted carboxamides and lactarns such as N-methylpyrrolidone and dimethylformamide. If the organic solvents are not miscible with water, a two-phase hydrogen
- Buffers, bases or acids can be added to the aqueous reaction medium.
- the reaction can, for example, be carried out at a pH of from 1 to 12, preferably from 2 to 10 and particularly preferably from 3 to 9.
- Suitable buffers are, in particular, phosphate buffers, but it is also possible to use carboxylic acids, carbonic acid, phosphoric acid and boric acid.
- suitable bases are alkali metal hydroxides and alkaline earth metal hydroxides, amines and alkali metal salts of carboxylic acids, carbonic acid, phosphoric acid and boric acid.
- Suitable acids are HC1, HBr, HI, HBF 4 , HC10 4 , carboxylic acids (unsubstituted, fluorinated or chlorinated acetic acid, benzoic acid, citric acid) , boric acid, phosphoric acid, methanesulfonic acid, sulfuric acid and carbonic acid.
- the bases and acids can also be soluble or insoluble polymers such as ion-exchange resins .
- the amount of bases, acids and/or buffers can be, for example, from 0 to 2, preferably from 0 to 1 and particularly preferably from 0 to 0.5, mol per litre of water.
- suitable organic solvents are esters and lactones such as ethyl acetate and methyl acetate and valerolactone; ketones such as acetone or methyl isobutyl ketone; halogenated hydrocarbons such as methylene chloride, chloroform, tetrachloroethane and chlorobenzene; ethers such as diethyl ether, diisobutyl ether, tetrahydrofuran and dioxane; sulfoxides and sulfones such as dimethyl sulfoxide, dimethyl sulfone, tetramethylene sulfone; N-substituted carboxamides and lactams such as N-methylpyrrolidone and dimethyl- formamide; and particularly alcohols.
- esters and lactones such as ethyl acetate and methyl acetate and valerolactone
- ketones such as acetone or methyl isobutyl ket
- an alcoholic reaction medium means the presence of an alcohol, either alone or in admixture with another organic solvent.
- Suitable alcohols are aliphatic, cyclo- aliphatic, cycloaliphatic-aliphatic and araliphatic alcohols.
- Some preferred examples are methanol, ethanol, n- or i-propanol, n-, i- or t-butanol, pentanol, hexanol, cyclohexanol, cyclohexanediol, hydroxymethylcyclohexane or dihydroxymethylcyclohexane, benzyl alcohol, ethylene glycol, diethylene glycol, propanediol, butanediol, ethylene glycol monomethyl ether or ethylene glycol monoethyl ether, and diethylene glycol monomethyl ether or diethylene glycol monoethyl ether.
- the proportion of an alcohol is preferably at least 30 per cent by volume, particularly preferably at least 50 per cent by volume and in particular at least 70 per cent by volume. Very particular preference is given to using only an alcohol.
- the catalytic properties of the diphosphine catalysts used can be influenced by addition of cocatalysts, modifiers, metal halides and ammonium halides. It can therefore be advantageous to add alkali metal or ammonium chlorides, bromides or iodides, for example LiCl, LiBr, Lil, Nal, NaBr or tetrabutylammonium iodide, to the reaction mixture. The amount can be, for example, from 0.001 to 5 mol per litre of solvent.
- Known modifiers are phthalimides and parabanic acid.
- the hydrogenation can be carried out continuously or batchwise in various types of reactor. Preference is given to reactors which allow comparatively good mixing and good heat removal, e.g. loop reactors. This type of reactor has been found to be particularly useful when using small amounts of catalyst.
- the hydrogenated organic compounds which can be prepared according to the invention are active substances or intermediates for preparing such substances, in particular in the production of pharmaceuticals and agrochemicals .
- o, o-dialkylarylamine derivatives in particular those having alkyl and/or alkoxyalkyl groups, act as fungicides, particularly as herbicides.
- the derivatives can be amine salts, acid amides, e.g. of chloroacetic acid, tertiary amines and ammonium salts (cf., for example, EP-A-0 077 755 and EP-A-0 115 470) .
- Example Al Preparation of (C 2 H 5 0 2 C-CH 2 CH 2 -0-CH 2 - ) 3 C-NCO (Al) A solution of 1 mmol of (C 2 H 5 0 2 C-CH 2 CH 2 -0-CH 2 -) 3 C-NH 2 (prepared as described by G.R. Newcome et al . , Aldrichimica Acta, 25 (1992) 31-8)] in toluene (7 ml per mmol) is added to an equimolar amount of carbonyldiimidazole and the mixture is stirred overnight. A mixture of isocyanate and imidazolylurea is formed. The solution is used directly for the reactions below.
- Example A2 Preparation of H 2 N-CH 2 CH 2 CH 2 -N[CH 2 CH 2 -N- (C 2 H 5 )] 2 (A2) a) A mixture of 1 ml (3.5 mmol) of N,N,N',N'- tetraethyldiethylenetriamine in 5 ml of acetonitrile and 938 mg (3.5 mmol) of N- (3-bromopropyl)phthalimide and 977 mg (7 mmol) of potassium carbonate is stirred at room temperature over the weekend.
- the reaction mixture is extracted with methylene chloride/water, the organic phase is dried over sodium sulfate and evaporated on a rotary evaporator and the crude product is purified by chromatography (silica gel Merck 60, eluant: 50 / 1 mixture of ethanol / triethylamine) .
- the product is obtained as an oil in a yield of 80%.
- Example Bla The procedure of Example Bla is repeated, except that 3 , 4-diphenylphosphinopyrrolidine (pyrphos) is used as starting compound.
- the reaction product is obtained in a yield of 63%.
- Example B3 Preparation of ligand K3 a) Preparation of the triester The procedure of Example Bla is repeated, except that
- Example Bib The procedure of Example Bib is repeated. The product is obtained as a white solid in a yield of 92%.
- a solution of 83 mg (0.133 mmol) of the amine ligand B in 1.5 ml of methylene chloride is added at 0 °C to a solution of 22 mg (0.133 mmol) of 1, 1 ' -carbodiimidazole in 2 ml of methylene chloride and the mixture is subsequently stirred at room temperature for 2 hours .
- 2 equivalents of N,N,N' ,N' -tetraethyldiethylenetriamine and 2 mg of dibutyltin dilaurate are then added and the mixture is stirred overnight .
- Example B7 Preparation of ligand K7 97 mg (0.335 mmol) of tetraamine A2 in 1.5 ml of methylene chloride are added at 0 °C to a solution of 58 mg (0.35 mmol) of 1, 1 '-carbodiimidazole in 4 ml of methylene chloride and the reaction mixture is subsequently stirred at room temperature for 1 hour. A solution of 154 mg (0.34 mmol) of (2S, 4S) - (- ) -4- diphenylphosphino-2- (diphenylphosphinomethyl) - pyrrolidine in 2 ml of methylene chloride is then added and the mixture is stirred under reflux for 6 hours.
- R H or K, Na: acetamidocinnamic acid (AC)
- All operations are carried out under argon as protective gas .
- the hydrogenations are carried out in a 25 ml glass flask (1 bar of hydrogen pressure) or a 50 ml steel autoclave (>1 bar of hydrogen pressure) provided with magnetic stirrer and a vacuum/gas connection.
- the hydrogenation solutions are introduced by means of a syringe and needle, in the case of the glass flask through a septum, in the case of the autoclave under a countercurrent of argon.
- the inert gas is displaced by hydrogen (glass apparatus: 4 cycles of vacuum, hydrogen at atmospheric pressure; steel autoclave: 4 cycles of pressurization with 5-10 bar of hydrogen and depressurization) .
- the hydrogenations are started by switching on the stirrer.
- pH 7 0.041 mol of Na 2 HP0 4 and 0.028 mol of KH 2 P0 4 /litre
- pH 8 0.063 mol of Na 2 HP0 4 and 0.004 mol of KH 2 P0 4 /litre .
- the ligand is placed in a vessel and dissolved while stirring with the aid of 0. IN NaOH (1 equivalent of NaOH per equivalent of carboxylic acid functions) . After addition of 1 ml of water, the ligand solution is added to [Rh(norbornadiene) 2 ]BF 4 and the mixture is stirred until a clear solution is obtained.
- the substrate solution is prepared as described in Method a, but is made up to 10 ml with water only after addition of the catalyst solution. This solution is transferred to a hydrogenation apparatus and hydrogenated.
- Method c Hydrogenation in water
- the ligand is placed in a vessel, suspended in 1 ml of water and dissolved by addition of methanesulfonic acid (1% by volume in water) (1 equivalent of methanesulfonic acid per equivalent of amine functions) .
- the ligand solution is added to [Rh (norbornadiene) 2 ]BF 4 and the mixture is stirred until a clear solution is obtained.
- the substrate solution is prepared as described in Method a) , but is made up to 10 ml with water only after addition of the catalyst solution. This solution is transferred to a hydrogenation apparatus and hydrogenated.
- the hydrogenation solution from Example C9 is, after the hydrogenation, evaporated to dryness under reduced pressure and the mixture is subsequently extracted with ethyl acetate and water (with phosphate buffer, pH 8) .
- the organic phases are collected, washed with water, dried over sodium sulfate and finally evaporated to dryness on a rotary evaporator. Analysis of the organic product indicates that more than 95% of the rhodium have been separated off.
- the reaction conditions are indicated in Table 1.
- MAC is used as substrate, while AC is used in all the others .
- the hydrogenation in Examples CI and CIO is carried out by Method a) , in Examples C2 to C7 by Method b) , and in Examples C7, C8, Cll, C12 and C15 by Method c) .
- the hydrogen pressure is 15 bar, in all the other examples 1 bar.
- the solvent is water; in Examples C8, C9, Cll, C12 and C15 it is methanol; and in Example C5 it is a mixture of 10 ml of water (phosphate buffer pH 8) and 7 ml of ethyl acetate (two-phase hydrogenation) .
- Reaction temperature in Examples C1-C5 and C10-C11: 25 °C; in Examples C6 to C9 and C12-C15: 40 °C.
- Examples C16-C23 Hydrogenation of folic acid 0.0025 mmol of ligand are dissolved in 5 ml of water and 0.5 ml of buffer pH 7 (0.041 mol of Na 2 HP0 4 and 0.028 mol of KH 2 P0 4 in 1 1 of water) . The carboxylic acid groups of the ligands are then reacted with 0.1N NaOH until a clear solution is formed. The resulting solution is added to 7.4 mg (0.02 mmol) of [Rh(NBD) 2 ]BF and stirred until a solution has formed (NBD is norbornadiene) .
- This solution is added to a solution of 2 mmol of folic acid disodium salt in 11 ml of water and 1.5 ml of buffer pH 7 and the mixture is transferred to a hydrogenation autoclave provided with a sparging stirrer by means of a syringe in a countercurrent of argon.
- the autoclave is closed, the argon is replaced by hydrogen and hydrogen is finally injected until the desired pressure has been reached.
- the hydrogen pressure is maintained by further supplies from the reservoir via a reducing valve.
- the hydrogenation is started by switching on the stirrer.
- the hydrogenation time reported is the time until the reaction stops (no longer any uptake of hydrogen) . Unless indicated otherwise, this corresponds to complete conversion of the folic acid.
- the pressure is 80 bar and the reaction temperature is 70 °C (30 °C in Example C21) .
- the molar ratio of substrate to catalyst (S/C) is 100 in Examples C16-C22 and is 1000 in Example C23.
- the optical yield DE is reported for the S,S configuration of folic acid. The results are summarized in Table 3.
- Footnotes 1) Buffer pH 6 : 0.01 mol of Na 2 HP0 and 0.071 mol of KH 2 P0 4 in 1 1 of water; at the end of the reaction, another 4 ml of IN KH 2 P0 4 are added.
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AU59846/00A AU5984600A (en) | 1999-07-14 | 2000-07-12 | Diphosphine ligands for metal complexes |
EP00945913A EP1194437A1 (en) | 1999-07-14 | 2000-07-12 | Diphosphine ligands for metal complexes |
JP2001509740A JP2003504376A (en) | 1999-07-14 | 2000-07-12 | Diphosphine ligands for metal complexes |
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
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US9127308B2 (en) | 2002-03-07 | 2015-09-08 | Atlas Genetics Limited | Nucleic acid probes, their synthesis and use |
CN112892604A (en) * | 2019-12-03 | 2021-06-04 | 中国科学院大连化学物理研究所 | Organic amine and CO2Heterogeneous catalysis method for preparing formamide |
Citations (6)
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---|---|---|---|---|
EP0329043A2 (en) * | 1988-02-19 | 1989-08-23 | Hoechst Aktiengesellschaft | Optically active rhodium-complexes of 3,4-bis(diarylphosphino)-pyrrolidines, and their use in the preparation of phosphinothricine by asymmetric hydrogenation |
EP0496699A1 (en) * | 1991-01-25 | 1992-07-29 | Ciba-Geigy Ag | Diphosphines containing silane groups, immobilized diphosphines and their use as hydrogenation catalysts |
EP0512416A2 (en) * | 1991-05-03 | 1992-11-11 | Hoechst Aktiengesellschaft | Homochiral diphosphines |
EP0729969A1 (en) * | 1995-02-24 | 1996-09-04 | Ciba-Geigy Ag | Silated ferrocene-diphosphine ligands, inorganic or polymeric organic support to which these ligands are bound and metal complexes thereof, and their preparation and use |
WO1997002232A1 (en) * | 1995-07-06 | 1997-01-23 | Novartis Ag | PROCESS FOR THE HYDROGENATION OF IMINES IN THE PRESENCE OF IMMOBILIZED Ir-DIPHOSPHINE CATALYSTS |
WO1998001457A1 (en) * | 1996-07-10 | 1998-01-15 | Novartis Ag | Functionalized ferrocenyldiphosphines, a process for their preparation and their use |
-
2000
- 2000-07-12 EP EP00945913A patent/EP1194437A1/en not_active Ceased
- 2000-07-12 WO PCT/EP2000/006658 patent/WO2001004131A1/en not_active Application Discontinuation
- 2000-07-12 JP JP2001509740A patent/JP2003504376A/en active Pending
- 2000-07-12 AU AU59846/00A patent/AU5984600A/en not_active Abandoned
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0329043A2 (en) * | 1988-02-19 | 1989-08-23 | Hoechst Aktiengesellschaft | Optically active rhodium-complexes of 3,4-bis(diarylphosphino)-pyrrolidines, and their use in the preparation of phosphinothricine by asymmetric hydrogenation |
EP0496699A1 (en) * | 1991-01-25 | 1992-07-29 | Ciba-Geigy Ag | Diphosphines containing silane groups, immobilized diphosphines and their use as hydrogenation catalysts |
EP0512416A2 (en) * | 1991-05-03 | 1992-11-11 | Hoechst Aktiengesellschaft | Homochiral diphosphines |
EP0729969A1 (en) * | 1995-02-24 | 1996-09-04 | Ciba-Geigy Ag | Silated ferrocene-diphosphine ligands, inorganic or polymeric organic support to which these ligands are bound and metal complexes thereof, and their preparation and use |
WO1997002232A1 (en) * | 1995-07-06 | 1997-01-23 | Novartis Ag | PROCESS FOR THE HYDROGENATION OF IMINES IN THE PRESENCE OF IMMOBILIZED Ir-DIPHOSPHINE CATALYSTS |
WO1998001457A1 (en) * | 1996-07-10 | 1998-01-15 | Novartis Ag | Functionalized ferrocenyldiphosphines, a process for their preparation and their use |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9127308B2 (en) | 2002-03-07 | 2015-09-08 | Atlas Genetics Limited | Nucleic acid probes, their synthesis and use |
US10094800B2 (en) | 2002-03-07 | 2018-10-09 | Atlas Genetics Limited | Assays and apparatus for detecting electrochemical active markers in an electric field |
CN112892604A (en) * | 2019-12-03 | 2021-06-04 | 中国科学院大连化学物理研究所 | Organic amine and CO2Heterogeneous catalysis method for preparing formamide |
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EP1194437A1 (en) | 2002-04-10 |
JP2003504376A (en) | 2003-02-04 |
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