CN114669333A - 一种催化α-季碳醛脱羰氢化的催化剂体系和催化方法 - Google Patents
一种催化α-季碳醛脱羰氢化的催化剂体系和催化方法 Download PDFInfo
- Publication number
- CN114669333A CN114669333A CN202210439122.5A CN202210439122A CN114669333A CN 114669333 A CN114669333 A CN 114669333A CN 202210439122 A CN202210439122 A CN 202210439122A CN 114669333 A CN114669333 A CN 114669333A
- Authority
- CN
- China
- Prior art keywords
- bis
- aldehyde
- alpha
- decarbonylation
- quaternary
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000006606 decarbonylation reaction Methods 0.000 title claims abstract description 98
- 230000006324 decarbonylation Effects 0.000 title claims abstract description 96
- 229910052799 carbon Inorganic materials 0.000 title claims abstract description 68
- 238000005984 hydrogenation reaction Methods 0.000 title claims abstract description 66
- -1 carbon aldehyde Chemical class 0.000 title claims abstract description 62
- 239000003054 catalyst Substances 0.000 title claims abstract description 52
- 238000000034 method Methods 0.000 title claims abstract description 50
- 239000003446 ligand Substances 0.000 claims abstract description 55
- 238000006243 chemical reaction Methods 0.000 claims abstract description 39
- 125000003172 aldehyde group Chemical group 0.000 claims abstract description 20
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229910052741 iridium Inorganic materials 0.000 claims abstract description 13
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 claims abstract description 13
- 238000010438 heat treatment Methods 0.000 claims abstract description 8
- 239000002904 solvent Substances 0.000 claims abstract description 7
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims abstract description 3
- 238000002156 mixing Methods 0.000 claims abstract description 3
- 230000008569 process Effects 0.000 claims abstract description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical group CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 73
- 229910052751 metal Inorganic materials 0.000 claims description 9
- 239000002184 metal Substances 0.000 claims description 9
- 239000008096 xylene Substances 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 5
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 claims description 4
- URLKBWYHVLBVBO-UHFFFAOYSA-N Para-Xylene Chemical group CC1=CC=C(C)C=C1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- RWGFKTVRMDUZSP-UHFFFAOYSA-N cumene Chemical compound CC(C)C1=CC=CC=C1 RWGFKTVRMDUZSP-UHFFFAOYSA-N 0.000 claims description 4
- 150000001924 cycloalkanes Chemical class 0.000 claims description 4
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 238000011065 in-situ storage Methods 0.000 claims description 4
- IVSZLXZYQVIEFR-UHFFFAOYSA-N m-xylene Chemical group CC1=CC=CC(C)=C1 IVSZLXZYQVIEFR-UHFFFAOYSA-N 0.000 claims description 4
- YTZKOQUCBOVLHL-UHFFFAOYSA-N tert-butylbenzene Chemical compound CC(C)(C)C1=CC=CC=C1 YTZKOQUCBOVLHL-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- XHYCFRBYCKMCNT-UHFFFAOYSA-N [2-[2-bis(3,4,5-trifluorophenyl)phosphanyl-6-methoxyphenyl]-3-methoxyphenyl]-bis(3,4,5-trifluorophenyl)phosphane Chemical compound COC=1C=CC=C(P(C=2C=C(F)C(F)=C(F)C=2)C=2C=C(F)C(F)=C(F)C=2)C=1C=1C(OC)=CC=CC=1P(C=1C=C(F)C(F)=C(F)C=1)C1=CC(F)=C(F)C(F)=C1 XHYCFRBYCKMCNT-UHFFFAOYSA-N 0.000 claims description 2
- JZCMGMXFWZWFRX-UHFFFAOYSA-N [2-[2-bis(3,4,5-trimethoxyphenyl)phosphanyl-6-methoxyphenyl]-3-methoxyphenyl]-bis(3,4,5-trimethoxyphenyl)phosphane Chemical compound COC=1C=CC=C(P(C=2C=C(OC)C(OC)=C(OC)C=2)C=2C=C(OC)C(OC)=C(OC)C=2)C=1C=1C(OC)=CC=CC=1P(C=1C=C(OC)C(OC)=C(OC)C=1)C1=CC(OC)=C(OC)C(OC)=C1 JZCMGMXFWZWFRX-UHFFFAOYSA-N 0.000 claims description 2
- SWMJWTAAPZTGDO-UHFFFAOYSA-N [2-[2-bis(3,5-dimethoxyphenyl)phosphanyl-6-methoxyphenyl]-3-methoxyphenyl]-bis(3,5-dimethoxyphenyl)phosphane Chemical compound COC1=CC(OC)=CC(P(C=2C=C(OC)C=C(OC)C=2)C=2C(=C(OC)C=CC=2)C=2C(=CC=CC=2OC)P(C=2C=C(OC)C=C(OC)C=2)C=2C=C(OC)C=C(OC)C=2)=C1 SWMJWTAAPZTGDO-UHFFFAOYSA-N 0.000 claims description 2
- IMUHNRWTDUVXOU-UHFFFAOYSA-N [2-[2-bis(3,5-dimethylphenyl)phosphanyl-6-methoxyphenyl]-3-methoxyphenyl]-bis(3,5-dimethylphenyl)phosphane Chemical compound COC=1C=CC=C(P(C=2C=C(C)C=C(C)C=2)C=2C=C(C)C=C(C)C=2)C=1C=1C(OC)=CC=CC=1P(C=1C=C(C)C=C(C)C=1)C1=CC(C)=CC(C)=C1 IMUHNRWTDUVXOU-UHFFFAOYSA-N 0.000 claims description 2
- PBYRAYONARLAQJ-UHFFFAOYSA-N [2-[2-bis(3,5-ditert-butylphenyl)phosphanyl-6-methoxyphenyl]-3-methoxyphenyl]-bis(3,5-ditert-butylphenyl)phosphane Chemical compound COC=1C=CC=C(P(C=2C=C(C=C(C=2)C(C)(C)C)C(C)(C)C)C=2C=C(C=C(C=2)C(C)(C)C)C(C)(C)C)C=1C=1C(OC)=CC=CC=1P(C=1C=C(C=C(C=1)C(C)(C)C)C(C)(C)C)C1=CC(C(C)(C)C)=CC(C(C)(C)C)=C1 PBYRAYONARLAQJ-UHFFFAOYSA-N 0.000 claims description 2
- JZQLSOZVSQIHEI-UHFFFAOYSA-N [2-[2-bis(4-methoxyphenyl)phosphanyl-6-methoxyphenyl]-3-methoxyphenyl]-bis(4-methoxyphenyl)phosphane Chemical compound C1=CC(OC)=CC=C1P(C=1C(=C(OC)C=CC=1)C=1C(=CC=CC=1OC)P(C=1C=CC(OC)=CC=1)C=1C=CC(OC)=CC=1)C1=CC=C(OC)C=C1 JZQLSOZVSQIHEI-UHFFFAOYSA-N 0.000 claims description 2
- SAPFRROREVCQOG-UHFFFAOYSA-N [2-[2-bis[3,5-bis(trifluoromethyl)phenyl]phosphanyl-6-methoxyphenyl]-3-methoxyphenyl]-bis[3,5-bis(trifluoromethyl)phenyl]phosphane Chemical compound COC=1C=CC=C(P(C=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)C=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)C=1C=1C(OC)=CC=CC=1P(C=1C=C(C=C(C=1)C(F)(F)F)C(F)(F)F)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 SAPFRROREVCQOG-UHFFFAOYSA-N 0.000 claims description 2
- 229930007927 cymene Natural products 0.000 claims description 2
- WDIIYWASEVHBBT-UHFFFAOYSA-N di(propan-2-yl)phosphane Chemical compound CC(C)PC(C)C WDIIYWASEVHBBT-UHFFFAOYSA-N 0.000 claims description 2
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 claims description 2
- HFPZCAJZSCWRBC-UHFFFAOYSA-N p-cymene Chemical compound CC(C)C1=CC=C(C)C=C1 HFPZCAJZSCWRBC-UHFFFAOYSA-N 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 150000003738 xylenes Chemical class 0.000 claims description 2
- 230000003197 catalytic effect Effects 0.000 abstract description 68
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 abstract description 6
- 125000000524 functional group Chemical group 0.000 abstract description 5
- 238000006555 catalytic reaction Methods 0.000 abstract description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 99
- 150000001875 compounds Chemical class 0.000 description 53
- 150000001299 aldehydes Chemical class 0.000 description 37
- 229940078552 o-xylene Drugs 0.000 description 34
- 238000004440 column chromatography Methods 0.000 description 28
- 238000005160 1H NMR spectroscopy Methods 0.000 description 26
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 25
- 238000012360 testing method Methods 0.000 description 23
- 230000000052 comparative effect Effects 0.000 description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-Bis(diphenylphosphino)propane Substances C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 239000000758 substrate Substances 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000004305 biphenyl Substances 0.000 description 4
- 235000010290 biphenyl Nutrition 0.000 description 4
- 239000012230 colorless oil Substances 0.000 description 4
- TXLHNFOLHRXMAU-UHFFFAOYSA-N 2-(4-benzylphenoxy)-n,n-diethylethanamine;hydron;chloride Chemical compound Cl.C1=CC(OCCN(CC)CC)=CC=C1CC1=CC=CC=C1 TXLHNFOLHRXMAU-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 238000006356 dehydrogenation reaction Methods 0.000 description 3
- 238000011068 loading method Methods 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- 150000003138 primary alcohols Chemical class 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- MPDGHEJMBKOTSU-YKLVYJNSSA-N 18beta-glycyrrhetic acid Chemical compound C([C@H]1C2=CC(=O)[C@H]34)[C@@](C)(C(O)=O)CC[C@]1(C)CC[C@@]2(C)[C@]4(C)CC[C@@H]1[C@]3(C)CC[C@H](O)C1(C)C MPDGHEJMBKOTSU-YKLVYJNSSA-N 0.000 description 2
- BCJVBDBJSMFBRW-UHFFFAOYSA-N 4-diphenylphosphanylbutyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCCP(C=1C=CC=CC=1)C1=CC=CC=C1 BCJVBDBJSMFBRW-UHFFFAOYSA-N 0.000 description 2
- MBVFRSJFKMJRHA-UHFFFAOYSA-N 4-fluoro-1-benzofuran-7-carbaldehyde Chemical group FC1=CC=C(C=O)C2=C1C=CO2 MBVFRSJFKMJRHA-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- GDMCOFXEPNHXJT-UHFFFAOYSA-N [5-(6-diphenylphosphanyl-2,3-dihydro-1,4-benzodioxin-5-yl)-2,3-dihydro-1,4-benzodioxin-6-yl]-diphenylphosphane Chemical compound O1CCOC(C=2C=3C=4OCCOC=4C=CC=3P(C=3C=CC=CC=3)C=3C=CC=CC=3)=C1C=CC=2P(C=1C=CC=CC=1)C1=CC=CC=C1 GDMCOFXEPNHXJT-UHFFFAOYSA-N 0.000 description 2
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 2
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- HHEAADYXPMHMCT-UHFFFAOYSA-N dpph Chemical compound [O-][N+](=O)C1=CC([N+](=O)[O-])=CC([N+]([O-])=O)=C1[N]N(C=1C=CC=CC=1)C1=CC=CC=C1 HHEAADYXPMHMCT-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 2
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
- 238000004293 19F NMR spectroscopy Methods 0.000 description 1
- MIJYXULNPSFWEK-GTOFXWBISA-N 3beta-hydroxyolean-12-en-28-oic acid Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CCC(C)(C)C[C@H]5C4=CC[C@@H]3[C@]21C MIJYXULNPSFWEK-GTOFXWBISA-N 0.000 description 1
- BTXXTMOWISPQSJ-UHFFFAOYSA-N 4,4,4-trifluorobutan-2-one Chemical compound CC(=O)CC(F)(F)F BTXXTMOWISPQSJ-UHFFFAOYSA-N 0.000 description 1
- MZFPAWGWFDGCHP-UHFFFAOYSA-N 5-diphenylphosphanylpentyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCCCP(C=1C=CC=CC=1)C1=CC=CC=C1 MZFPAWGWFDGCHP-UHFFFAOYSA-N 0.000 description 1
- BQACOLQNOUYJCE-FYZZASKESA-N Abietic acid Natural products CC(C)C1=CC2=CC[C@]3(C)[C@](C)(CCC[C@@]3(C)C(=O)O)[C@H]2CC1 BQACOLQNOUYJCE-FYZZASKESA-N 0.000 description 1
- RSWGJHLUYNHPMX-UHFFFAOYSA-N Abietic-Saeure Natural products C12CCC(C(C)C)=CC2=CCC2C1(C)CCCC2(C)C(O)=O RSWGJHLUYNHPMX-UHFFFAOYSA-N 0.000 description 1
- DNQVOXPMLAZUQZ-UHFFFAOYSA-N C=O.C12CC3CC(CC(C1)C3)C2 Chemical compound C=O.C12CC3CC(CC(C1)C3)C2 DNQVOXPMLAZUQZ-UHFFFAOYSA-N 0.000 description 1
- JKLISIRFYWXLQG-UHFFFAOYSA-N Epioleonolsaeure Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C)(C)CC5C4CCC3C21C JKLISIRFYWXLQG-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- MPDGHEJMBKOTSU-UHFFFAOYSA-N Glycyrrhetinsaeure Natural products C12C(=O)C=C3C4CC(C)(C(O)=O)CCC4(C)CCC3(C)C1(C)CCC1C2(C)CCC(O)C1(C)C MPDGHEJMBKOTSU-UHFFFAOYSA-N 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- YBRJHZPWOMJYKQ-UHFFFAOYSA-N Oleanolic acid Natural products CC1(C)CC2C3=CCC4C5(C)CCC(O)C(C)(C)C5CCC4(C)C3(C)CCC2(C1)C(=O)O YBRJHZPWOMJYKQ-UHFFFAOYSA-N 0.000 description 1
- MIJYXULNPSFWEK-UHFFFAOYSA-N Oleanolinsaeure Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C)(C)CC5C4=CCC3C21C MIJYXULNPSFWEK-UHFFFAOYSA-N 0.000 description 1
- GRTJBNJOHNTQBO-UHFFFAOYSA-N [2-(2-diphenylphosphanylphenyl)phenyl]-diphenylphosphane Chemical group C1=CC=CC=C1P(C=1C(=CC=CC=1)C=1C(=CC=CC=1)P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 GRTJBNJOHNTQBO-UHFFFAOYSA-N 0.000 description 1
- RZZDRSHFIVOQAF-UHFFFAOYSA-N [4-(5-diphenylphosphanyl-1,3-benzodioxol-4-yl)-1,3-benzodioxol-5-yl]-diphenylphosphane Chemical compound C=12OCOC2=CC=C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)C=1C1=C2OCOC2=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RZZDRSHFIVOQAF-UHFFFAOYSA-N 0.000 description 1
- DZULQZKFBAHSRX-UHFFFAOYSA-N adamantane-1-carbaldehyde Chemical compound C1C(C2)CC3CC2CC1(C=O)C3 DZULQZKFBAHSRX-UHFFFAOYSA-N 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000003934 aromatic aldehydes Chemical class 0.000 description 1
- 238000006254 arylation reaction Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- CNXMDTWQWLGCPE-UHFFFAOYSA-N ditert-butyl-(2-phenylphenyl)phosphane Chemical compound CC(C)(C)P(C(C)(C)C)C1=CC=CC=C1C1=CC=CC=C1 CNXMDTWQWLGCPE-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229960003720 enoxolone Drugs 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000003682 fluorination reaction Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 1
- 125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910052755 nonmetal Inorganic materials 0.000 description 1
- 229940100243 oleanolic acid Drugs 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- HZLWUYJLOIAQFC-UHFFFAOYSA-N prosapogenin PS-A Natural products C12CC(C)(C)CCC2(C(O)=O)CCC(C2(CCC3C4(C)C)C)(C)C1=CCC2C3(C)CCC4OC1OCC(O)C(O)C1O HZLWUYJLOIAQFC-UHFFFAOYSA-N 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- QBERHIJABFXGRZ-UHFFFAOYSA-M rhodium;triphenylphosphane;chloride Chemical compound [Cl-].[Rh].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QBERHIJABFXGRZ-UHFFFAOYSA-M 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 1
- 239000011995 wilkinson's catalyst Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Images
Classifications
-
- 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
- B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
- B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
- B01J31/2409—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring with more than one complexing phosphine-P atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C1/00—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon
- C07C1/20—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from organic compounds containing only oxygen atoms as heteroatoms
- C07C1/207—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from organic compounds containing only oxygen atoms as heteroatoms from carbonyl compounds
- C07C1/2076—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from organic compounds containing only oxygen atoms as heteroatoms from carbonyl compounds by a transformation in which at least one -C(=O)- moiety is eliminated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C13/00—Cyclic hydrocarbons containing rings other than, or in addition to, six-membered aromatic rings
- C07C13/28—Polycyclic hydrocarbons or acyclic hydrocarbon derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C13/00—Cyclic hydrocarbons containing rings other than, or in addition to, six-membered aromatic rings
- C07C13/28—Polycyclic hydrocarbons or acyclic hydrocarbon derivatives thereof
- C07C13/32—Polycyclic hydrocarbons or acyclic hydrocarbon derivatives thereof with condensed rings
- C07C13/54—Polycyclic hydrocarbons or acyclic hydrocarbon derivatives thereof with condensed rings with three condensed rings
- C07C13/573—Polycyclic hydrocarbons or acyclic hydrocarbon derivatives thereof with condensed rings with three condensed rings with three six-membered rings
- C07C13/60—Completely or partially hydrogenated phenanthrenes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C15/00—Cyclic hydrocarbons containing only six-membered aromatic rings as cyclic parts
- C07C15/02—Monocyclic hydrocarbons
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C269/06—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups by reactions not involving the formation of carbamate groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/12—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/74—Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring
- C07C69/753—Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring of polycyclic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/04—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
- C07D211/16—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with acylated ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
- C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/26—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D211/62—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J63/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
- C07J63/008—Expansion of ring D by one atom, e.g. D homo steroids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/36—Systems containing two condensed rings the rings having more than two atoms in common
- C07C2602/44—Systems containing two condensed rings the rings having more than two atoms in common the bicyclo ring system containing eight carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/22—Ortho- or ortho- and peri-condensed systems containing three rings containing only six-membered rings
- C07C2603/26—Phenanthrenes; Hydrogenated phenanthrenes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/56—Ring systems containing bridged rings
- C07C2603/58—Ring systems containing bridged rings containing three rings
- C07C2603/70—Ring systems containing bridged rings containing three rings containing only six-membered rings
- C07C2603/74—Adamantanes
Abstract
本申请属于α‑季碳醛催化技术领域,尤其涉及一种催化α‑季碳醛脱羰氢化的催化剂体系和催化方法。本申请第一方面提供了一种催化α‑季碳醛脱羰氢化的催化剂体系,由金属铱和BIPHEP配体组成。本申请第二方面提供了一种催化α‑季碳醛脱羰氢化的方法,包括以下步骤:将α‑季碳醛与溶剂混合,在催化剂存在的条件下进行加热反应,得到与所述α‑季碳醛对应的醛基α位由季碳转化成一个次甲基且其手性碳构型保持的产物;所述催化剂由金属铱和BIPHEP配体组成。本申请提供的催化剂体系和催化方法,可有效解决现有仍没有一种高效的、官能团兼容性良好的对大位阻α‑季醛脱羰氢化的催化方法。
Description
技术领域
本申请属于过渡金属催化的有机合成技术领域,尤其涉及一种催化α-季碳醛脱羰氢化的催化剂体系和催化方法。
背景技术
醛类化合物是一类重要的化合物,是非常容易获得的大宗化学品之一并且其在药物、食品、饲料领域也有良好的应用前景。醛也是一类活性官能团,可以发生多种化学反应:氧化、还原、偶联、缩合以及加成等反应;同时醛基或者醛基与胺类作用(原位形成亚胺)可以作为一个导向基,在金属催化条件下可以实现导向氟化、胺化、硼化、烷基化、芳基化等转化,当实现这些转化后作为导向基的醛基需要脱除。所以发展一种对醛进行高效脱除的策略具有重要意义,而对于α-手性季醛的化合物脱羰后产物手性可以保持将更加具有挑战性。
目前文献报道醛脱羰常用的催化剂是wilkinson催化剂,其在脂肪醛与芳香醛脱羰都展现出良好的催化性能(Tsuji,J.et al.Tetrahedron Lett.1965,6,3969;Ohno,K.etal.J.Am.Chem.Soc.1968,90,99.),但是催化剂用量需要大于一个当量,此催化剂价格昂贵,所以限制了其使用。另外一个醛脱羰催化效率比较高的体系是Rh/dppp(Doughty,D.H.et al.J.Am.Chem.Soc.1978,100,7083.),此催化体系对苯甲醛脱羰TON最高可达1×105以上。虽然该催化体系展现出了极高的催化效率,但是对于大位阻α-季醛脱羰没有任何催化效果。对大位阻的α-季醛脱羰反应,到目前为止只有一篇文献报道,该文献报道了Pd/C催化金刚烷甲醛脱羰生成金刚烷的反应(T.Shirai et al.Synlett 2019 30 972-976.)。该催化体系虽然实现了α-季醛的脱羰,但是底物仅仅适用于结构特殊的金刚烷甲醛。除了底物特殊外,该反应需要比较高的催化剂上载量(10%mol Pd/C)与较长的反应时间(48.0h)。Iwai等人报道了一例[IrCl(cod)]2(5mol%Ir)与三苯基膦共催化α-季碳醛脱羰氢化,其唯一的底物产率仅3%的产物(T.Iwai et al.Chem.Commun.,2008,6215)。
到目前为止,对大位阻α-季醛脱羰还没有一种高效的、官能团兼容性良好的催化体系被开发出来,特别是对于α-手性季醛脱羰后产物手性保持的方法更是亟待研究。
发明内容
鉴于此,本申请提供了一种催化α-季碳醛脱羰氢化的催化剂体系和催化方法,可有效解决现有仍没有一种高效的、官能团兼容性良好的对大位阻α-季醛脱羰氢化的催化方法。
本申请第一方面提供了一种催化α-季碳醛脱羰氢化的催化剂体系,由金属铱和BIPHEP配体组成;
所述金属铱为[Ir(COD)Cl]2或/和[Ir(COE)Cl]2;
所述BIPHEP配体选自(6,6'-二甲氧基联苯-2,2'-基)双(二苯基膦)、(6,6′-二甲氧基联苯-2,2′-二基)二[双(4-甲氧基苯基)膦]、(6,6′-二甲氧基联苯-2,2′-二基)二[双(3,5-二甲氧基苯基)膦]、(6,6′-二甲氧基联苯-2,2′-二基)二[双(3,5-二甲基苯基)膦]、(6,6′-二甲氧基联苯-2,2′-二基)二[双(3,5-二叔丁基苯基)膦]、(6,6′-二甲氧基联苯-2,2′-二基)二[双(3,5-二苯基苯基)膦]、(6,6′-二甲氧基联苯-2,2′-二基)二[双(3,5-二三氟甲基苯基)膦]、(6,6′-二甲氧基联苯-2,2′-二基)二[双(3,4,5-三氟苯基)膦]、(6,6′-二甲氧基联苯-2,2′-二基)二[双(3,4,5-三甲氧基苯基)膦]、(6,6'-二甲氧基联苯-2,2'-基)双(二异丙基膦)、1,1'-联萘-2,2'-双二苯膦、5,5'-双(二苯基磷)-4,4'-二-1,3-苯并二氧和[(5,6),(5',6')-双(乙烯二氧)联苯-2,2'-基]二苯基磷中的一种或多种。
优选的,所述金属铱和所述BIPHEP配体的摩尔比为1:(0.5~3)。
进一步的,所述α-季碳醛具有式I所示结构;
其中,R1、R2和R3各自独立地为取代或非取代烷基、取代或非取代环烷烃、取代或非取代杂环烷烃。
进一步的,所述α-季碳醛为通过式II原位脱除一分子的氢气产生如所述式I中的醛基,所述原位脱除一分子的氢气的催化剂采用脱除羰基相同的催化剂(即所述催化剂体系)。
其中,R1、R2和R3各自独立地为取代或非取代烷基、取代或非取代环烷烃、取代或非取代杂环烷烃。
进一步的,所述α-季碳醛选自直链α-季碳醛、环状α-季碳醛以及含有杂原子的α-季碳醛中的一种或多种。
更进一步的,所述R1、所述R2和所述R3各自独立地选自卤素、C1~12烷基、C1~12卤代烷基、C1~12芳基取代烷基、C1~12氨基取代烷基、C1~12烷氧基取代烷基、C1~12吡啶取代烷基、C1~12噻吩取代烷基、C1~12呋喃取代烷基、C3~12环烷基、C3~12氨基取代环烷基、C12~18稠和环;其中的杂原子为N和O卤素中的一种或多种,一个或多个。
优选的,所述α-季碳醛选自:
本申请第二方面提供了一种催化α-季碳醛脱羰氢化的方法,包括以下步骤:
将α-季碳醛与溶剂混合,在催化剂存在的条件下进行加热反应,得到与所述α-季碳醛对应的醛基α位手性碳构型保持产物;所述催化剂为所述催化剂体系;所述α-季碳醛为上述种类的α-季碳醛。
具体的,所述醛基α位手性碳构型保持产物为与所述α-季碳醛对应的醛基α位由季碳转化成一个次甲基且其手性碳构型保持的产物。
具体的,所述催化α-季碳醛脱羰氢化的方法路线如下:
具体的,由上述反应可知,所述R1、所述R2和所述R3均不参与反应,同时对上述脱羰反应也不产生任何的影响,因此只需式I所示化合物中存在醛基,在上述催化剂体系中,即可发生上述脱羰反应。
优选的,所述α-季碳醛、所述金属铱与所述BIPHEP配体的摩尔比为100:(0.1~10):(0.05~30)。
优选的,所述溶剂选自邻二甲苯、间二甲苯、对二甲苯、混合二甲苯、异丙苯、乙苯、叔丁基苯、伞花烃、二乙二醇二甲醚中的一种或多种。优选的,所述加热反应的温度为130~190℃,所述加热反应的时间为5~30小时。
更优选的,所述溶剂为邻二甲苯。
更优选的,所述加热反应的温度为170℃。
具体的,本申请提供的催化α-季碳醛脱羰氢化的方法在开放体系中进行,底物(式I所示化合物)、催化剂体系与溶剂在手套箱进行称量与量取后加入到史莱克反应管,反应管拿出手套箱后用氮气气球保护。
本申请发现以金属铱-BIPHEP为催化体系,实现了大位阻α-季醛脱羰,对于的α-手性季醛可得到醛基α位手性碳构型保持产物的方法。反应条件简单;反应的底物适用性强,对于直链或者环状以及含有杂原子的α-季醛均可实现脱羰;对于的α-手性季醛可得到醛基α位手性碳构型保持产物,并且产率良好。
附图说明
为了更清楚地说明本申请实施例或现有技术中的技术方案,下面将对实施例或现有技术描述中所需要使用的附图作简单地介绍。
图1为本申请提供的催化α-季碳醛脱羰氢化的合成路线;
图2为本申请测试例提供的不同催化剂配体对α-季醛(式1-1所示化合物)脱羰的转化率和收率;
图3为本申请测试例提供的不同α-季碳醛脱羰氢化后得到的醛基α位手性碳构型保持产物结构式和收率结果图;
图4为本申请测试例提供的不同α-季碳醛脱羰氢化后得到的醛基α位手性碳构型保持产物结构式和收率结果图;
图5为本申请测试例提供的不同α-季碳醛结构进行脱羰氢化的收率结果图;
图6为本申请对比例3提供的不同催化剂配体催化α-季碳醛脱羰氢化的转化率和产率结果。
具体实施方式
本申请提供了一种催化α-季碳醛脱羰氢化的催化剂体系和催化方法,用于解决现有技术中没有一种高效的、官能团兼容性良好的对大位阻α-季醛脱羰氢化的催化方法的缺陷。
下面将对本申请实施例中的技术方案进行清楚、完整地描述,显然,所描述的实施例仅仅是本申请一部分实施例,而不是全部的实施例。基于本申请中的实施例,本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例,都属于本申请保护的范围。
本申请实施例所用的α-季碳醛和BIPHEP配体可通过现有文献公开的方法制备得到。
实施例1
本申请实施例提供了式1-1所示化合物脱羰氢化的催化方法,具体包括:
取一个25mL史莱克反应管并用高温枪烘干,然后将其移入手套箱,在手套箱中将[Ir(COD)Cl]2(10.3mg,0.0153mmol),L7(56.9mg,0.0603mmol)与1-1(303.8mg,1.0013mmol)依次加入该反应管中,最后加入o-Xylene(1.5mL)。温度升到170℃反应18小时后,反应液直接柱层析柱层析(PE/EA=20:1)得到2-1((229.1mg,83%yield),淡黄色油状物。1H NMR(400MHz,CDCl3)δ7.32–7.23(m,3H),7.23–7.15(m,1H),7.17–7.09(m,2H),4.06(br.s,2H),2.63(t,J=12.8Hz,2H),2.53(d,J=7.0Hz,2H),1.81–1.53(m,3H),1.45(s,9H),1.14(qd,J=12.6,4.2Hz,2H)。13C NMR(101MHz,CDCl3)δ154.99,140.36,129.23,128.35,126.05,79.33,44.11,43.27,38.30,32.11,28.59。MS(EI):m/z(%)275(M+,2.97),57(100)。
实施例2
本申请实施例提供了式1-2所示化合物脱羰氢化的催化方法,具体包括:
参考实施例1,[Ir(COD)Cl]2(10.2mg,0.0152mmol),L7(56.8mg,0.0602mmol.),1-2(338.2mg,1.0023mmol.),o-Xylene(1.5mL),170℃反应18小时。柱层析(PE/EA=10:1)得到2-2(290.1mg,94%),白色固体。1H NMR(400MHz,CDCl3)δ7.41–7.23(m,7H,7.24–7.15(m,1),7.16–7.08(m,2),5.12(s,2),4.16(br.s,2H),2.72(m,2H),2.54(d,J=7.0Hz,2H),1.84–1.53(m,3H),1.25–1.06(m,2H)。13C NMR(101MHz,CDCl3)δ155.37,140.17,137.07,129.21,128.56,128.36,128.00,127.92,67.03,44.29,43.18,38.16,31.99。IR(neat):2926,2854,1691,1240,1185,1060cm-1。MS(EI):m/z(%)275(M+,2.97),57(100)。HRMS(ESI+):m/z calc’d for(M+H)+:310.1802,found 310.1804。MP:42.9-43.4℃。
实施例3
本申请实施例提供了式1-3所示化合物脱羰氢化的催化方法,具体包括:
参考实施例1,Ir(COD)Cl]2(10.1mg,0.0150mmol.),L7(56.8mg,0.0602mmol.),1-3(308.4mg,1.0033mmol.),o-Xylene(1.5mL),170℃反应18小时。柱层析(PE/EA=10:1)得到2-3((270.2mg,96%yield)。1H NMR(400MHz,CDCl3)δ7.38(s,5H),7.31–7.26(m,2H),7.23–7.17(m,1H),7.18–7.09(m,2H),4.71(d,J=12.2Hz,1H),3.72(d,J=13.6Hz,1H),3.04–2.62(m,2H),2.57(t,J=5.6Hz,2H),1.99–1.71(m,2H),1.59(d,J=13.0Hz,1H),1.45–0.93(m,2H)。13C NMR(101MHz,CDCl3)δ170.31,139.95,136.44,129.44,129.10,128.42,128.34,126.86,126.09,48.05,43.03,42.47,38.37,32.69,31.85。IR(neat):2916,2850,1628,1431,1284,966cm-1。MS(EI):m/z(%)279(M+,41.45),105(100)。HRMS(ESI+):m/z calc’d for(M+H)+:280.1696,found 280.1694。
实施例4
本申请实施例提供了式1-4所示化合物脱羰氢化的催化方法,具体包括:
参考实施例1,[Ir(COD)Cl]2(10.0mg,0.0149mmol.),L7(56.5mg,0.0599mmol.),1-4(358.1mg,1.0017mmol.),o-Xylene(1.5mL),170℃反应18小时。柱层析(PE/EA=10:1)得到2-4(316.2mg,96%yield)。1H NMR(400MHz,CDCl3)δ7.61(d,J=8.2Hz,2H),7.29(d,J=8.0Hz,2H),7.28–7.20(m,2H),7.19–7.13(m,1H),7.10–7.00(m,2H),3.79–3.69(m,2H),2.50(d,J=6.7Hz,2H),2.41(s,3H),2.17(t,J=11.8Hz,2H),1.77–1.59(m,1H),1.48–1.05(m,3H)。13C NMR(101MHz,CDCl3)δ143.45,139.91,133.20,129.63,129.09,128.37,127.81,126.14,46.55,42.72,37.43,31.37,21.60。IR(neat):2914,2846,1336,1159,937,814cm-1。MS(EI):m/z(%)329(M+,31.91),91(100)。HRMS(ESI+):m/z calc’d for(M+H)+:330.1522,found 330.1519。MP:97.7-98.1℃。
实施例5
本申请实施例提供了式1-5所示化合物脱羰氢化的催化方法,具体包括:
参考实施例1,[Ir(COD)Cl]2(10.0mg,0.0149mmol.),L7(56.7mg,0.0601mmol.),1-5(228.1mg,1.0035mmol.),o-Xylene(1.5mL),170℃反18小时。柱层析(PE/EA=20:1)得到2-5(139.8mg,70%),淡黄色油状物。1H NMR(400MHz,CDCl3)δ4.05(br.s,2H),2.68(t,J=12.2Hz,2H),1.65–1.54(m,1H),1.53-1.45(m,10H),1.08(qd,J=12.5,4.2Hz,2H),0.93(d,J=6.5Hz,3H).13C NMR(101MHz,CDCl3)δ155.05,79.22,44.39,34.16,31.10,28.62,22.01.MS(EI):m/z(%)199(M+,3.81),57(100)
实施例6
本申请实施例提供式1-6所示化合物脱羰氢化的催化方法,具体包括:
参考实施例1,[Ir(COD)Cl]2(10.0mg,0.0149mmol.),L7(56.7mg,0.0601mmol.),aldehyde 3-6(347.9mg,1.0041mmol.),o-Xylene(1.5mL),170℃反应18小时。柱层析(PE/EA=20:1)得到2-6(249.8mg,78%yield),淡黄色油状物。1H NMR(400MHz,CDCl3)δ7.26–7.18(m,2H),6.75–6.60(m,3H),4.08(br.s,2H),3.41–3.26(m,2H),2.90(s,3H),2.69(t,J=12.0Hz,2H),1.76–1.63(m,2H),1.60–1.46(m,3H),1.45(s,9H),1.15(qd,J=12.4,4.3Hz,2H).13C NMR(101MHz,CDCl3)δ154.98,149.33,129.32,116.24,112.36,79.38,50.36,44.10,38.31,34.19,32.98,32.31,28.60.IR(neat):2923,1689,1600,1506,1169,866cm-1。MS(ESI):m/z(%)319(M+H)+,8.85),263(100).HRMS(ESI+):m/z calc’d for(M+H)+:319.2380,found 319.2378。
实施例7
本申请实施例提供式1-7所示化合物脱羰氢化的催化方法,具体包括:
参考实施例1,[Ir(COD)Cl]2(10.2mg,0.0152mmol.),L7(56.6mg,0.0600mmol.),1-7(273.3mg,1.0071mmol.),o-Xylene(1.5mL),170℃反应24小时。柱层析(PE/EA=10:1)得到2-7(180.8mg,74%yield),淡黄色油状物。1H NMR(400MHz,CDCl3)δ4.07(br.s,2H),3.42(t,J=6.2Hz,2H),3.33(s,3H),2.69(t,J=11.7Hz,2H),1.74–1.59(m,2H),1.60–1.48(m,3H),1.45(s,9H)1.10(qd,J=12.4,4.3Hz,2H).13C NMR(101MHz,CDCl3)δ154.98,79.27,70.26,58.71,44.06,36.30,32.98,32.23,28.57.MS(EI):m/z(%)243(M+,0.79),57(100).
实施例8
本申请实施例提供式1-8所示化合物脱羰氢化的催化方法,具体包括:
参考实施例1,[Ir(COD)Cl]2(10.3mg,0.0153mmol.),L7(56.7mg,0.0601mmol.),1-8(260.8mg,1.0057mmol.),o-Xylene(1.5mL),170℃反应18小时。柱层析(PE/EA=10:1)得到2-8(187.6mg,81%yield),淡黄色油状物。1H NMR(400MHz,CDCl3)δ4.57(t,J=5.8Hz,1H),4.46(t,J=5.7Hz,1H),4.09(br.s,2H),2.68(t,J=13.4Hz,2H),1.79–1.51(m,5H),1.46(s,9H),1.14(qd,J=12.4,4.4Hz,2H).13C NMR(101MHz,CDCl3)δ154.96,81.98(d,J=164.4Hz),79.39,44.01,37.04(d,J=19.4Hz),32.60(d,J=3.9Hz),32.08,28.57.19F NMR(377MHz,CDCl3)δ-219.18.MS(EI):m/z(%)231(M+,3.86),57(100).
实施例9
本申请实施例提供式1-9所示化合物脱羰氢化的催化方法,具体包括:
参考实施例1,[Ir(COD)Cl]2(10.1mg,0.0150mmol),L7(56.9mg,0.0603mmol),1-9(286.6mg,1.0044mmol),o-Xylene(1.5mL),170℃反应18小时。柱层析(PE/EA=10:1)得到2-9(203.2mg,79%yield),无色油状物。1H NMR(400MHz,CDCl3)δ4.14(q,J=7.1Hz,2H),4.02(s,2H),2.83(t,J=11.8Hz,2H),2.43(tt,J=11.0,3.8Hz,1H),1.97–1.84(m,2H),1.62(qd,J=12.9,12.2,4.2Hz,2H),1.46(s,9H),1.26(t,J=7.1Hz,3H).13C NMR(101MHz,CDCl3)δ174.70,154.82,79.65,60.59,43.17,41.26,28.54,28.08,14.31.MS(EI):m/z(%)257(M+,0.2),57(100).
实施例10
本申请实施例提供式1-10所示化合物脱羰氢化的催化方法,具体包括:
参考实施例1,[Ir(COD)Cl]2(16.9mg,0.0252mmol),L7(56.5mg,0.1002mmol),1-10(304.6mg,1.0040mmol),o-Xylene(1.5mL)。170℃反应36小时。柱层析(PE/EA=20/1)得到2-10(187.5mg,68%)。1H NMR(600MHz,DMSO-d6,80℃)δ7.29(t,J=7.1Hz,2H),7.19(d,J=7.5Hz,3H),3.75(d,J=13.1Hz,2H),2.82(t,J=12.0Hz,1H),2.62–2.54(m,1H),1.82–1.51(m,3H),1.42–1.24(m,10H),1.18(q,J=11.3Hz,1H).13C NMR(151MHz,DMSO-d6,80℃)δ154.55,140.45,129.33,128.65,126.32,78.87,49.53,44.66,39.96,37.84,30.86,28.65,24.94.MS(ESI):m/z(%)298(M+Na)+,100),298(100).
实施例11
本申请实施例提供式1-11所示化合物脱羰氢化的催化方法,具体包括:
参考实施例1,[Ir(COD)Cl]2(10.2mg,0.0152mmol),L7(56.5mg,0.0599mmol),1-11(202.5mg,1.0010mmol),o-Xylene(1.5mL),170℃反应24小时。柱层析(PE=100%)得到2-11(119.9mg,69%yield),无色油状物。(沸点与二甲苯接近,后处理损失核磁收率90%)。1H NMR(600MHz,CDCl3)δ7.26(t,J=7.4Hz,2H),7.17(t,J=7.3Hz,1H),7.13(d,J=7.5Hz,2H),2.47(d,J=7.1Hz,2H),1.82–1.58(m,5H),1.56–1.48(m,1H),1.24–1.10(m,3H),1.01–0.88(m,2H).13C NMR(151MHz,CDCl3)δ141.51,129.32,128.16,125.69,44.29,39.93,33.30,26.72,26.47.MS(EI):m/z(%)174(M+,63.62),91(100).
实施例12
本申请实施例提供式1-12所示化合物脱羰氢化的催化方法,具体包括:
参考实施例1,[Ir(COD)Cl]2(10.3mg,0.0153mmol),L7(56.8mg,0.0602mmol),1-12(289.9mg,1.0mmol),o-Xylene(1.5mL),170℃18小时。柱层析(PE/EA=10:1)得2-12(211.8mg,81%)。1H NMR of Two Rotamers(400MHz,CDCl3)δ7.35–7.26(m,2H),7.21(t,J=7.8Hz,1H),7.16(d,J=7.5Hz,2H),3.65–3.36(m,2H),3.25(hept,J=9.2,8.2Hz,1H),3.09–2.91(m,1H),2.80–2.56(m,2H),2.55–2.29(m,1H),2.00–1.85(m,1H),1.76–1.51(m,2H),1.45(s,9H).13C NMR of Two Rotamers(101MHz,CDCl3)δ154.75,140.44,128.77,128.52,126.23,79.13 and 79.09,51.35 and 51.09,45.72 and 45.29,40.86 and40.15,39.32,31.53 and 30.83,28.63.MS(EI):m/z(%)261(M+,3.23),57(100).
实施例13
本申请实施例提供式1-13所示化合物脱羰氢化的催化方法,具体包括:
参考实施例1,[Ir(COD)Cl]2(10.1mg,0.0150mmol),L7(56.8mg,0.0602mmol),aldehyde 3-16(275.8mg,1.0016mmol),o-Xylene(1.5mL),170℃反应18小时。柱层析(PE/EA=10:1)得到2-13(203.2mg,82%yield),无色油状物。1H NMR(400MHz,CDCl3)δ7.36–7.25(m,2H),7.25–7.16(m,1H),7.17–7.10(m,2H),3.99(t,J=8.3Hz,2H),3.65(dd,J=8.6,5.3Hz,2H),3.07–2.78(m,2H),2.86–2.73(m,1H),1.44(s,9H).13C NMR(101MHz,CDCl3)δ156.57,139.45,128.68,128.51,126.47,79.34,54.30,40.39,30.00,28.53.IR(neat):2964,1684,1407,1366,1135,862cm-1。MS(EI):m/z(%)247(M+,2.33),57(100)。HRMS(ESI+):m/z calc’d for(M+H)+:248.1645,found 248.1644.
实施例14
本申请实施例提供式1-14所示化合物脱羰氢化的催化方法,具体包括:
参考实施例1,[Ir(COD)Cl]2(10.2mg,0.0152mmol.),L7(56.7mg,0.0601mmol.),1-14(196.5mg,1.0055mmol.),o-Xylene(1.5mL),170℃反应18小时。柱层析(PE/EA=50:1)得到2-14(145.0mg,86%yield),无色油状物。1H NMR(400MHz,CDCl3)δ3.63(s,3H),1.84–1.68(m,6H),1.66–1.52(m,7H).13C NMR(151MHz,CDCl3)δ178.81,51.67,38.41,28.17,25.49,23.84.MS(EI):m/z(%)168(M+,68.57),108.9(100).
实施例15
本申请实施例提供式1-15所示化合物脱羰氢化的催化方法,具体包括:
参考实施例1,[Ir(COD)Cl]2(10.1mg,0.0150mmol.),L7(56.9mg,0.0603mmol.),1-15(223.5mg,1.0055mmol.),o-Xylene(1.5mL),170℃反应24小时。柱层析(PE/EA=50:1)得到2-13(168.4mg,86%yield),白色固体。1H NMR(400MHz,CDCl3)δ3.65(s,3H),2.01(s,3H),1.89(d,J=3.1Hz,6H),1.80–1.63(m,6H).13C NMR(101MHz,CDCl3)δ178.36,51.67,40.83,38.99,36.64,28.08.MS(EI):m/z(%)194(M+,14.81),135(100).
实施例16
本申请实施例提供式1-16所示化合物脱羰氢化的催化方法,具体包括:
参考实施例1,[Ir(COD)Cl]2(10.3mg,0.0153mmol.),L7(56.5mg,0.0599mmol.),1-16(196.5mg,1.0055mmol.),o-Xylene(1.5mL),170℃反应18小时。2-16与o-Xylene Rf值与沸点接近。核磁收率:86%。
实施例17
本申请实施例提供式1-17所示化合物脱羰氢化的催化方法,具体包括:
参考实施例1,[Ir(COD)Cl]2(10.2mg,0.0152mmol),L7(56.7mg,0.0601mmol),1-17(218.4mg,1.0054mmol.),o-Xylene(1.5mL),170℃反应18小时。柱层析(PE/EA=10/1)得到2-17(174.9mg,92%yield)。1H NMR(400MHz,CDCl3)δ7.81(dd,J=5.4,3.0Hz,2H),7.70(dd,J=5.5,3.1Hz,2H),4.54(hept,J=7.0Hz,1H),1.49(d,J=6.9Hz,6H).13C NMR(151MHz,CDCl3)δ168.49,133.86,132.23,123.09,43.10,20.24.MS(EI):m/z(%)189(M+,9.23),174(100).
实施例18
本申请实施例提供式1-18所示化合物脱羰氢化的催化方法,具体包括:
参考实施例1,[Ir(COD)Cl]2(10.2mg,0.0152mmol.),L7(56.5mg,0.0599mmol.),1-18(188.5mg,1.0067mmol.)and o-Xylene(1.5mL),170℃反应18小时。柱层析(PE/EA=20/1)得到2-18(119.3mg,74%yield),淡黄色固体。(沸点低)。1H NMR(600MHz,CDCl3)δ4.38(br.s,1H),3.76(br.s,1H),1.44(s,9H),1.13(d,J=6.6Hz,6H).13C NMR(151MHz,CDCl3)δ155.29,79.05,42.62,28.56,23.23.MS(EI):101((M–C3H9N)+,36.57),59(100).
实施例19
本申请实施例提供式1-19所示化合物脱羰氢化的催化方法,具体包括:
参考实施例1,[Ir(COD)Cl]2(10.0mg,0.0149mmol.),L9(56.8mg,0.0602mmol.),aldehyde 1-19(294.4mg,1.0035mmol.)ino-Xylene(1.5mL),170℃反应18小时。柱层析(PE/EA=10/1)得到2-19(218.4mg,82%yield),淡黄色油状物。1H NMR(400MHz,CDCl3)δ7.30(dd,J=1.9,0.8Hz,1H),6.28(dd,J=3.0,1.9Hz,1H),5.99(d,J=2.7Hz,1H),4.08(br.s,2H),2.67(t,J=13.0Hz,2H),2.55(d,J=7.0Hz,2H),1.77(ttt,J=10.9,7.1,3.6Hz,1H),1.71–1.58(m,2H),1.45(s,9H),1.14(qd,J=12.5,4.4Hz,2H).13C NMR(101MHz,CDCl3)δ154.97,154.34,141.14,110.19,106.22,79.35,35.84,35.00,32.00,28.57.IR(neat):2930,1690,1421,1234,1159,1009cm-1。MS(EI):265((M+,3.06),57(100).HRMS(ESI+):m/z calc’d for(M+Na)+:288.1570,found 288.1568.
实施例20
本申请实施例提供式1-20所示化合物脱羰氢化的催化方法,具体包括:
参考实施例1,[Ir(COD)Cl]2(34.2mg,0.051mmol.),L7(189.3mg,0.20mmol.),1-20(303.9mg,0.9984mmol.),o-Xylene(1.5mL),170℃反应36小时。柱层析(PE/EA=2/1)得到2-20(131.2mg,48%)。1H NMR(400MHz,CDCl3)δ8.50(d,J=5.7Hz,2H),7.07(d,J=6.0Hz,2H),4.09(br.s,2H),2.66(t,J=12.9Hz,2H),2.54(d,J=7.2Hz,2H),1.84–1.64(m,1H),1.67–1.54(m,2H),1.45(s,9H),1.16(qd,J=12.6,4.1Hz,2H).13C NMR(151MHz,CDCl3)δ154.88,149.78,149.22,124.63,79.46,44.19,43.64,42.52,37.50,31.96,28.54.IR(neat):2929,2854,1688,1421,1160,1065cm-1。MS(ESI):277((M+H)+,33.26),221(100).HRMS(ESI+):m/z calc’d for(M+H)+:277.1911,found 277.1909.
实施例21
本申请实施例提供式1-21所示化合物脱羰氢化的催化方法,具体包括:
参考实施例1,[Ir(COD)Cl]2(10.3mg,0.0153mmol.),L7(56.6mg,0.0600mmol.),1-21(309.0mg,0.9995mmol.),o-Xylene(1.5mL).,170℃反应18小时。柱层析(PE/EA=10/1)得到2-21(186.2mg,66%yield),淡黄色固体。1H NMR(400MHz,CDCl3)δ7.13(dd,J=5.1,1.2Hz,1H),6.92(dd,J=5.1,3.4Hz,1H),6.76(dd,J=3.4,1.1Hz,1H),4.07(br.s,2H),2.75(d,J=6.7Hz,2H),2.66(t,J=11.8Hz,2H),1.78–1.60(m,3H),1.45(s,9H),1.14(qd,J=13.0,4.0Hz,2H).13C NMR(101MHz,CDCl3)δ154.94,142.83,126.85,125.33,123.43,79.36,43.96,38.70,36.94,31.95,28.57.IR(neat):2922,1682,1424,1365,1238,1150cm-1。MS(ESI):332((M+Na)+,332(100).HRMS(ESI+):m/z calc’d for(M+Na)+:304.1342,found304.1339.MP:33.1-33.9℃。
实施例22
本申请实施例提供式1-22所示化合物脱羰氢化的催化方法,具体包括:
参考实施例1,[Ir(COD)Cl]2(17.2mg,0.0256mmol.),L7(94.2mg,0.0999mmol.),1-22(284.2mg,0.9992mmol.),o-Xylene(1.5mL),170℃反应24小时。柱层析(PE)得到2-22(210.3mg,82%)。1H NMR(400MHz,CDCl3)δ7.16(d,J=8.1Hz,1H),6.98(dd,J=8.1,1.6Hz,2H),6.91–6.86(m,1H),2.94–2.85(m,3H),2.81(hept,J=6.92Hz,1H),2.25(dt,J=12.9,2.8Hz,1H),2.01–1.88(m,2H),1.87–1.71(m,1H),1.69(ddd,J=12.8,4.7,2.2Hz,1H),1.64–1.43(m,4H),1.38(td,J=13.1,3.5Hz,1H),1.22(d,J=6.9Hz,6H),1.17(s,3H),1.00(d,J=7.6Hz,3H).13C NMR(101MHz,CDCl3)δ147.31,145.55,135.20,127.11,124.43,123.93,44.58,38.76,37.42,34.08,33.61,33.23,30.50,25.70,24.71,24.14(d,J=2.0Hz),18.21,15.28.MS(EI):256(M+,27.76),159(100).
实施例23
本申请实施例提供式1-23所示化合物脱羰氢化的催化方法,具体包括:
参考实施例1,[Ir(COD)Cl]2(16.6mg,0.0247mmol.),L7(94.7mg,0.1004mmol.),1-23(276.5mg,0.4982mmol.),o-Xylene(2.0mL),170℃反应36小时。柱层析(PE=100%)得到2-23(157.9mg mg,60%yield),白色固体。1H NMR(600MHz,CDCl3)δ5.19(t,J=3.7Hz,1H),3.19(dd,J=11.3,4.4Hz,1H),2.34(dt,J=13.7,4.7Hz,1H),1.91–1.84(m,2H),1.80(qd,J=13.2,3.4Hz,1H),1.70(tt,J=14.1,4.7Hz,1H),1.66–1.61(m,1H),1.61–1.51(m,6H),1.49–1.41(m,3H),1.42–1.30(m,3H),1.29–1.17(m,3H),1.11(s,3H),1.10–1.05(m,1H),1.02–0.97(m,1H),0.92(s,3H),0.91(s,3H),0.90–0.88(m,12H),0.87(s,3H),0.86(s,3H),0.75(s,3H),0.71(d,J=1.9Hz,1H),0.03(s,6H).13C NMR(151MHz,CDCl3)δ146.06,121.32,79.60,55.46,47.90,45.09,42.56,41.02,39.47,39.26,38.59,37.13,35.85,33.85,33.79,33.27,31.34,31.21,28.72,28.15,27.80,26.09,25.23,24.01,23.51,22.41,18.75,18.28,17.61,16.31,15.54,-3.57,-4.74.IR(neat):2926,2858,1461,1386,1249,1101,1072,833cm-1。HRMS(ESI+):m/z calc’d for(M+H)+:527.4643,found527.4644.MP:204.2-205.2℃。
实施例24
本申请实施例提供式1-24所示化合物脱羰氢化的催化方法,具体包括:
参考实施例1,[Ir(COD)Cl]2(5.1mg,0.0076mmol.),L7(28.1mg,0.0298mmol.),1-24(285.1mg,0.5010mmol.),,o-Xylene(1.0mL),170℃反应18小时。柱层析(PE=100%)得到2-24(260.5mg,96%yield),白色固体。1H NMR(400MHz,CDCl3)δ5.59(s,1H),3.19(dd,J=11.5,4.6Hz,1H),2.73(dt,J=13.5,3.6Hz,1H),2.32(s,1H),2.12–1.88(m,2H),1.82(td,J=13.7,4.7Hz,1H),1.74–1.53(m,4H),1.54–1.36(m,6H),1.36(s,3H),1.34–1.22(m,3H),1.13(d,J=2.0Hz,6H),1.10–0.93(m,3H),0.91(s,3H),0.89(d,J=2.7Hz,12H),0.83(s,3H),0.77(s,3H),0.67(d,J=10.3Hz,1H),0.03(d,J=2.3Hz,6H).13C NMR(151MHz,CDCl3)δ200.62,170.38,128.16,79.42,62.02,55.17,51.82,45.52,43.44,41.53,40.99,39.86,39.28,37.15,33.51,33.00,32.53,30.77,28.87,28.64,27.75,26.80,26.76,26.07,23.48,22.53,18.83,18.26,17.84,16.57,16.24,-3.55,-4.79.IR(neat):2929,2857,1664,1254,1208,1088,1068,890,833cm-1。HRMS(ESI+):m/z calc’d for(M+H)+:541.4435,found 541.4430.MP:244.4–245.5℃。
实施例25
本申请实施例提供式1-25所示化合物脱羰氢化的催化方法,具体包括:
参考实施例1,[Ir(COD)Cl]2(5.1mg,0.0076mmol.),L7(28.6mg,0.0303mmol.),1-25(228.4mg,0.5023mmol.),o-Xylene(1.0mL),170℃反应18小时。柱层析(PE/EA=10/1)得到2-25(169.1mg,79%)。1H NMR(400MHz,CDCl3)δ5.64(s,1H),2.96(ddd,J=13.4,6.8,4.1Hz,1H),2.63(ddd,J=16.9,11.1,7.2Hz,1H),2.44(s,1H),2.36(dt,J=15.7,5.2Hz,1H),2.12–1.98(m,2H),1.85(td,J=13.6,4.3Hz,1H),1.79–1.64(m,1H),1.64–1.50(m,4H),1.52–1.38(m,4H),1.37(s,3H),1.36–1.26(m,3H),1.27(s,3H),1.24–1.15(m,4H),1.16–1.05(m,7H),1.05–0.96(m,1H),0.89(d,J=6.2Hz,3H),0.85(s,3H).13C NMR(151MHz,CDCl3)δ217.18,199.58,170.90,127.93,61.07,55.44,51.80,47.79,45.25,43.50,41.52,40.87,39.82,36.74,34.27,33.41,32.46,32.18,30.65,28.83,26.74,26.68,26.50,23.33,22.43,21.46,18.88,18.58,15.74.IR(neat):2922,2857,1720,1703,1659,1343,1164,926,815cm-1.MS(ESI):426((M+H)+,426(100).HRMS(ESI+):m/z calc’d for(M+H)+:425.3414,found 425.3413.
对比例1
本申请对比例提供式2-26的制备方法,合成路线如下,具体包括:
向2-24(541mg,1.0mmol)的5mL四氢呋喃溶液中加入TBAF(3.0mL,1.0M/THF,3.0mmol)。在50℃下搅拌24小时。用20mL饱和NaHCO3水溶液猝灭反应,用20mL乙酸乙酯萃取3次,用盐水洗涤合并有机层,用Na2SO4干燥,过滤,减压浓缩。通柱层析纯化(PE/EA=5/1),得到产物2-26(325mg,76%yield),白色固体。1H NMR(400MHz,CDCl3)δ5.60(s,1H),3.22(dd,J=11.0,5.2Hz,1H),2.78(d,J=13.5Hz,1H),2.34(s,1H),2.14–1.94(m,2H),1.83(td,J=13.8,4.4Hz,1H),1.74–1.56(m,5H),1.55–1.37(m,6H),1.36(s,3H),1.35–1.22(m,2H),1.21–1.06(m,8H),1.04–0.92(m,5H),0.88(d,J=6.2Hz,3H),0.83(s,3H),0.81(s,3H),0.74–0.65(m,1H).13C NMR(151MHz,Chloroform-d)δ200.54,170.56,128.07,78.81,61.88,55.05,51.81,45.48,43.44,41.50,40.94,39.25,37.18,33.47,32.89,30.73,28.85,27.41,26.75(d,J=2.7Hz),23.45,22.51,18.79,17.61,16.49,15.73.MS(ESI):450((M+Na)+,450(100)。
实施例26
本申请实施例提供式5-1所示化合物脱羰氢化的催化方法,合成路线如下,具体包括:
取一个25mL史莱克反应管并用高温枪烘干,然后将其移入手套箱,在手套箱中将[Ir(COD)Cl]2(10.2mg,0.0152mmol.),L7(56.9mg,0.0603mmol.),上述5-1所示化合物(303.8mg,1.0013mmol)依次加入该反应管中,最后加入o-Xylene(1.5mL)。温度升到170℃反应24小时后,反应液直接柱层析(PE/EA=20:1)得到4-1(154.7mg,57%yield),淡黄色油状物。1H NMR(400MHz,CDCl3)δ7.33–7.24(m,2H),7.24–7.15(m,1H),7.17–7.08(m,2H),4.07(br.s,2H),2.63(t,J=12.8Hz,2H),2.53(d,J=6.9Hz,2H),1.75–1.55(m,3H),1.45(s,9H),1.14(qd,J=12.5,4.0Hz,2H).
实施例27
本申请实施例提供式3-2所示化合物脱羰氢化的催化方法,合成路线如下,具体包括:
参考实施例27,[Ir(COD)Cl]2(10.3mg,0.0153mmol.),L7(56.7mg,0.0601mmol.),上述3-2所示化合物(223.9mg,1.0013mmol.),o-Xylene(1.5mL)。170℃反应24小时。柱层析(PE/EA=50/1)得到2-15(166.6mg,86%yield)。
实施例28
本申请实施例提供式3-3所示化合物脱羰氢化的催化方法,合成路线如下,具体包括:
参考实施例27,Ir(COD)Cl]2(10.1mg,0.0150mmol.),L9(56.5mg,0.0599mmol.),aldehyde上述3-3所示化合物(221.1mg,1.0092mmol.),o-Xylene(1.5mL)。170℃反应24小时。柱层析(PE/EA=20/1)得到2-17(159.6mg,84%)。
实施例29
本申请实施例提供式3-3所示化合物脱羰氢化的催化方法,合成路线如下,具体包括:
参考实施例27,[Ir(COD)Cl]2(5.1mg,0.0076mmol.),L7(28.1mg,0.0298mmol.),上述3-3所示化合物(285.6mg,0.5mmol),o-Xylene(1.0mL)。170℃反应24小时。柱层析(PE/EA=20/1)得到2-24(239.9mg,89%),白色固体。
测试例
本测试例提供了不同的催化剂配体对α-季醛(式1-1所示化合物)脱羰效率试验,以上述合成路线的式1-1所示化合物为原料,[Ir(COD)Cl2]为金属催化剂,筛选不同的催化剂配体骨架,合成路线如下:
1、测定不同催化剂配体对α-季醛(式1-1所示化合物)脱羰的转化率和收率(收率通过NMR计算),其中,催化剂配体上载量为12mol%,结果如图2和表1所示。
从图2和表1所示,不同催化剂配体对大位阻α-季醛的脱羰产率有着明显的差别。单齿配体考察了Ph3P,Cy3P,CyJohnphos,JohnPhos,除了Ph3P有3%的产物生成,其他几个单齿配体均没有催化效果。紧接着测试了双齿配体,本测试例首先筛选了商业可得价格低廉的直链型双齿配体DPPE,DPPP,DPPB,DPPPe,DPPH,实验结果显示使用DPPE配体可以得到28%产物,而其他几个配体催化效果较差或者几乎没有效果。接下来,本测试例测试了其他不同骨架双齿配体:2,2'-双(二苯基磷)联苯、1,2-双(二苯基膦基)苯、1,8-双(二苯基膦)萘、4,5-双二苯基膦-9,9-二甲基氧杂蒽(XantPhos),通过实验结果,本测试例发现联苯型配体2,2'-双(二苯基磷)联苯可以得到44%的收率,而其他几个配体催化效果远远低于联苯配体。由于联苯型配体展现出明显的优势,所以本测试例接下来又测试了其他几种联苯型配体:(6,6'-二甲氧基联苯-2,2'-基)双(二苯基膦)(MeO-BIPHEP)、5,5'-双(二苯基磷)-4,4'-二-1,3-苯并二氧(SEGPHOS)、6,6'-双(二苯基磷)-2,2',3,3'-四氢-5,5'-二-1,4-苯并二辛烷(SYNPHOS)以及1,1'-联萘-2,2'-双二苯膦(BINAP),通过实验结果,本测试例可以看出MeO-BIPHEP,SEGPHOS与SYNPHOS三个配体催化脱羰得到产物的收率分别为65%,64%和62%,这三个配体的催化效果优于BINAP的54%;而MeO-BIPHEP的催化效果要比SEGPHOS与SYNPHOS有微弱的优势,所以本测试例选择MeO-BIPHEP作为骨架,对该类型配体继续优化反应条件。
3、选择MeO-BIPHEP作为骨架,上述合成路线中式1-1所示化合物为α-季碳醛,该MeO-BIPHEP配体L如表1所示。对该类型配体继续优化反应条件。
反应条件:反应在25mL Schlenk管中进行,在170℃下,用本测试例的式1-1所示化合物(1.0mmol)、[Ir(COD)Cl]2(0.015mmol)配体(0.06mmol)和邻二甲苯(1.5mL)在18h内进行,产率通过以均三甲苯为内标物的粗反应混合物的NMR分析确定。b.单独产量。c.150mgD.10mol%P/C负载[Ir(COD)Cl]2。E.50mol%P/C负载[Ir(COD)Cl]2。
其中,表1中配体催化剂L的结构式如下:
表1不同的配体脱羰产率的结果
从表1可知,基于MeO-BIPHEP类型配体,考察了不同配体L2到L10,本测试例发现配体L7的催化效率最高,核磁收率90%,分离收率可以得到83%。同时本测试例也考察了醛脱羰经典催化体系Rh/dppp与Rh(Ph3P)3Cl,在大位阻醛脱羰中Rh(Ph3P)3Cl催化活性较低,核磁收率仅为6%,而Rh/dppp体系则完全没有催化活性。另外本测试例还考察了Pd/C的催化体系,实验结果表明,即使将Pd/C的催化剂上载量升到50mol%,脱羰产物只有32%,而原料则基本分解完全。此催化体系在大位阻醛的脱羰效率上远远低于本申请的催化体系金属铱-BIPHEP体系。最后通过对照实验得知,金属铱与配体缺一不可,二者结合才有催化活性。
4、按照以下合成路线的条件,测定不同α-季碳醛的脱羰氢化的选择范围,不同α-季碳醛脱羰氢化后得到的醛基α位手性碳构型保持产物结构式如图3~图4所示,通过以下合成路线测定不同α-季碳醛脱羰氢化得到对应醛基α位手性碳构型保持产物的产率,产率结果如图3~图4所示。
反应条件:上述式1的α-季碳醛(1.0mmol),[Ir(COD)Cl]2(0.015mmol),L7(0.06mmol),o-Xylene(1.5mL),170℃,18h.分离收率。b 24h.c 36h.d[Ir(COD)Cl](0.025mmol),L7(0.1mmol).e[Ir(COD)Cl](0.05mmol),L7(0.2mmol).fo-Xylene(1.0mL).go-Xylene(2.0mL).h 1(0.5mmol).i核磁收率。
不同α-季碳醛中,哌啶环氮原子的不同保护基如Ts,Cbz,Bz均可以得到90%以上的脱羰产物;底物中含有甲基、氮、氧、氟与酯基等基团兼容性良好;对于无杂原子的环状醛同样可以得到比较高的收率;五元环与四元环以及含有刚性环的大位阻醛在该催化体系下同样可以较高收率脱羰;除了环状醛,链状α-季醛也表现出较高的催化效率;对于杂环噻吩,吡啶,呋喃都可以兼容。另外值得注意的是,对于天然产物松香酸、甘草次酸、齐墩果酸衍生的α-手性季醛脱羰后醛基邻位的手性碳原子构型保持。进一步通过对2-26单晶衍射确定了脱羰后构型保持。本测试例测到化合物1-25未被保护的羟基在Ir-L7催化下生成一个含有酮羰基结构的化合物2-25,说明此催化体系不仅可以脱羰还可以对一级醇和二级醇脱氢生成相应的醛和酮,基于此结果,本测试例说明本申请提供的催化体系可以对伯醇进行脱氢生成醛,然后继续对醛进行脱羰。
5、按照以下合成路线的条件,测定不同α-季碳醛的脱羰氢化的选择范围。
合成图5中式2-1所示化合物、式2-15所示化合物、式2-17所示化合物的反应条件:上述式3所示化合物的α-季碳醛(1.0mmol),[Ir(COD)C1]2(0.015mmo1),L7(0.06mmol),o-Xylene(1.5mL),170℃反应24h。
合成图5中式2-24所示化合物的反应条件:上述式3所示化合物的α-季碳醛(0.5mmol),[Ir(COD)Cl]2(0.0075mmol),L7(0.03mmol),o-Xylene(1.0mL),170℃反应24h。实验结果表明,伯醇的脱氢脱羰在Ir-L7催化体系下可以顺利进行,对于手性的底物(上述式3-3所示化合物的α-季碳醛)可以顺利脱氢脱羰得到2-24,同样对于羟基β位手性碳构型保持。
对比例2
本申请对比例提供了采用不同催化剂配体催化α-季碳醛脱羰氢化的试验,具体包括:
按照以下合成路线,采用表2中催化剂配体L对α-季碳醛进行脱羰氢化。
表2不同的配体脱羰产率的结果
Entry | L | Conv. | Yield |
1 | DPPE | 4% | NA |
2 | DPPP | 30% | trace |
3 | DPPB | 8% | NA |
4 | DPPPent. | 93% | NA |
5 | DPPH | 2% | NA |
6 | DPPF | 26% | NA |
7 | XantPhos | 45% | 23% |
8 | Binap | 6% | NA |
对比例3
本申请本申请对比例提供了采用不同催化剂配体催化α-季碳醛脱羰氢化的试验,具体包括:
按照以下合成路线,采用图6提供的催化剂配体L对α-季碳醛进行脱羰氢化,不同催化剂配体催化α-季碳醛脱羰氢化的转化率和产率如图6所示。
对比例4
本申请本申请对比例提供了采用不同催化剂配体催化不同α-季碳醛脱羰氢化的试验,具体包括:
按照以下合成路线,采用表3提供的α-季碳醛M和催化剂配体L对进行脱羰氢化试验,不同催化剂配体催化不同α-季碳醛脱羰氢化的转化率和产率结果如表3所示。
表3不同的配体脱羰产率的结果
表3中“-”为不添加催化剂配体。
从表2~表3和图6数据可知,采用非BIPHEP配体或者采用非金属铱组成的催化剂体系无法催化α-季碳醛脱羰氢化,可见,本申请的催化剂体系中金属铱与配体缺一不可,二者结合才有催化催化α-季碳醛脱羰氢化的活性。
以上所述仅是本申请的优选实施方式,应当指出,对于本技术领域的普通技术人员来说,在不脱离本申请原理的前提下,还可以作出若干改进和润饰,这些改进和润饰也应视为本申请的保护范围。
Claims (10)
1.一种催化α-季碳醛脱羰氢化的催化剂体系,其特征在于,由金属铱和BIPHEP配体组成;
所述金属铱为[Ir(COD)Cl]2或/和[Ir(COE)Cl]2;
所述BIPHEP配体选自(6,6'-二甲氧基联苯-2,2'-基)双(二苯基膦)、(6,6′-二甲氧基联苯-2,2′-二基)二[双(4-甲氧基苯基)膦]、(6,6′-二甲氧基联苯-2,2′-二基)二[双(3,5-二甲氧基苯基)膦]、(6,6′-二甲氧基联苯-2,2′-二基)二[双(3,5-二甲基苯基)膦]、(6,6′-二甲氧基联苯-2,2′-二基)二[双(3,5-二叔丁基苯基)膦]、(6,6′-二甲氧基联苯-2,2′-二基)二[双(3,5-二苯基苯基)膦]、(6,6′-二甲氧基联苯-2,2′-二基)二[双(3,5-二三氟甲基苯基)膦]、(6,6′-二甲氧基联苯-2,2′-二基)二[双(3,4,5-三氟苯基)膦]、(6,6′-二甲氧基联苯-2,2′-二基)二[双(3,4,5-三甲氧基苯基)膦]、(6,6'-二甲氧基联苯-2,2'-基)双(二异丙基膦)、1,1'-联萘-2,2'-双二苯膦、5,5'-双(二苯基磷)-4,4'-二-1,3-苯并二氧和[(5,6),(5',6')-双(乙烯二氧)联苯-2,2'-基]二苯基磷中的一种或多种。
2.根据权利要求1所述的催化剂体系,其特征在于,所述金属铱原子和所述BIPHEP配体的摩尔比为1:(0.5~3)。
5.根据权利要求3所述的催化剂体系,其特征在于,所述R1、所述R2和所述R3各自独立地选自卤素、C1~12烷基、C1~12卤代烷基、C1~12芳基取代烷基、C1~12氨基取代烷基、C1~12烷氧基取代烷基、C1~12吡啶取代烷基、C1~12噻吩取代烷基、C1~12呋喃取代烷基、C3~12环烷基、C3~12氨基取代环烷基、C12~18稠和环;其中的杂原子为N和O卤素中的一种或多种,一个或多个。
7.一种催化α-季碳醛脱羰氢化的方法,其特征在于,包括以下步骤:
将α-季碳醛与溶剂混合,在催化剂存在的条件下进行加热反应,得到与所述α-季碳醛对应的醛基α位由季碳转化成一个次甲基且其手性碳构型保持的产物;所述催化剂为权利要求1或2所述的催化剂体系;所述α-季碳醛为权利要求3~6任意一项所述的α-季碳醛。
8.根据权利要求7所述的方法,其特征在于,所述α-季碳醛、所述金属铱与所述BIPHEP配体的摩尔比为100:(0.1~10):(0.05~30)。
9.根据权利要求7所述的方法,其特征在于,所述溶剂选自邻二甲苯、间二甲苯、对二甲苯、混合二甲苯、异丙苯、乙苯、叔丁基苯、伞花烃和二乙二醇二甲醚中的一种或多种。
10.根据权利要求7所述的方法,其特征在于,所述加热反应的温度为130~190℃,所述加热反应的时间为5~30小时。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210439122.5A CN114669333B (zh) | 2022-04-25 | 2022-04-25 | 一种催化α-季碳醛脱羰氢化的催化剂体系和催化方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210439122.5A CN114669333B (zh) | 2022-04-25 | 2022-04-25 | 一种催化α-季碳醛脱羰氢化的催化剂体系和催化方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN114669333A true CN114669333A (zh) | 2022-06-28 |
CN114669333B CN114669333B (zh) | 2023-06-23 |
Family
ID=82079869
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202210439122.5A Active CN114669333B (zh) | 2022-04-25 | 2022-04-25 | 一种催化α-季碳醛脱羰氢化的催化剂体系和催化方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN114669333B (zh) |
Citations (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2645101A1 (en) * | 1998-07-10 | 2000-01-20 | Stephen L. Buchwald | Ligands for metals and metal-catalyzed processes |
CN1468852A (zh) * | 2003-05-30 | 2004-01-21 | 中国科学院大连化学物理研究所 | 对映选择性铱催化氢化取代芳香吡啶环和吡嗪环的方法 |
WO2004084834A2 (en) * | 2003-03-24 | 2004-10-07 | The University Of North Carolina At Chapel Hill | Chiral porous metal phosphonates for heterogeneous asymmetric catalysis |
US20050070714A1 (en) * | 2003-09-29 | 2005-03-31 | Kurt Puentener | Process for the production of chiral propionic acid derivatives |
CN1909964A (zh) * | 2004-09-15 | 2007-02-07 | Lg化学株式会社 | 含磷催化剂组合物以及使用该组合物的醛化反应的方法 |
JP2007161609A (ja) * | 2005-12-09 | 2007-06-28 | Chiba Univ | 新規不斉イリジウム触媒の製造方法とこれらを用いる光学活性β−ヒドロキシ−α−アミノ酸誘導体の製造方法 |
WO2010146172A2 (en) * | 2009-06-19 | 2010-12-23 | Lek Pharmaceuticals D.D. | NEW SYNTHETIC ROUTE FOR THE PREPARATION OF α-AMINO BORONIC ACID DERIVATIVES VIA SUBSTITUTED ALK-1-YNES |
WO2011033022A2 (en) * | 2009-09-17 | 2011-03-24 | Universita' Degli Studi Di Udine | Osmium complexes usable as catalysts for the reduction of carbonyl compounds |
WO2012175837A1 (fr) * | 2011-06-24 | 2012-12-27 | Diverchim | PROCÉDÉS DE PRÉPARATION D'ACIDES α- ET β-AMINOPHOSPHORÉS ET LEURS DÉRIVÉS |
CN105566081A (zh) * | 2015-12-15 | 2016-05-11 | 上海华谊(集团)公司 | 烯烃氢甲酰化制备醛的方法 |
WO2018060512A1 (en) * | 2016-09-30 | 2018-04-05 | Patheon Austria Gmbh & Co Kg | Process for preparing chiral amines |
CN110551037A (zh) * | 2018-05-31 | 2019-12-10 | 中国科学院大连化学物理研究所 | 一种铱/手性双膦体系催化亚胺不对称氢化方法 |
CN111099986A (zh) * | 2019-12-13 | 2020-05-05 | 郑州大学 | 氢化反应方法 |
WO2021083018A1 (zh) * | 2019-10-30 | 2021-05-06 | 浙江九洲药业股份有限公司 | 吡啶环上3-位取代手性螺环胺基膦配体制备方法及其应用 |
-
2022
- 2022-04-25 CN CN202210439122.5A patent/CN114669333B/zh active Active
Patent Citations (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2645101A1 (en) * | 1998-07-10 | 2000-01-20 | Stephen L. Buchwald | Ligands for metals and metal-catalyzed processes |
WO2004084834A2 (en) * | 2003-03-24 | 2004-10-07 | The University Of North Carolina At Chapel Hill | Chiral porous metal phosphonates for heterogeneous asymmetric catalysis |
CN1468852A (zh) * | 2003-05-30 | 2004-01-21 | 中国科学院大连化学物理研究所 | 对映选择性铱催化氢化取代芳香吡啶环和吡嗪环的方法 |
US20050070714A1 (en) * | 2003-09-29 | 2005-03-31 | Kurt Puentener | Process for the production of chiral propionic acid derivatives |
CN1909964A (zh) * | 2004-09-15 | 2007-02-07 | Lg化学株式会社 | 含磷催化剂组合物以及使用该组合物的醛化反应的方法 |
JP2007161609A (ja) * | 2005-12-09 | 2007-06-28 | Chiba Univ | 新規不斉イリジウム触媒の製造方法とこれらを用いる光学活性β−ヒドロキシ−α−アミノ酸誘導体の製造方法 |
WO2010146172A2 (en) * | 2009-06-19 | 2010-12-23 | Lek Pharmaceuticals D.D. | NEW SYNTHETIC ROUTE FOR THE PREPARATION OF α-AMINO BORONIC ACID DERIVATIVES VIA SUBSTITUTED ALK-1-YNES |
WO2011033022A2 (en) * | 2009-09-17 | 2011-03-24 | Universita' Degli Studi Di Udine | Osmium complexes usable as catalysts for the reduction of carbonyl compounds |
WO2012175837A1 (fr) * | 2011-06-24 | 2012-12-27 | Diverchim | PROCÉDÉS DE PRÉPARATION D'ACIDES α- ET β-AMINOPHOSPHORÉS ET LEURS DÉRIVÉS |
CN105566081A (zh) * | 2015-12-15 | 2016-05-11 | 上海华谊(集团)公司 | 烯烃氢甲酰化制备醛的方法 |
WO2018060512A1 (en) * | 2016-09-30 | 2018-04-05 | Patheon Austria Gmbh & Co Kg | Process for preparing chiral amines |
CN110551037A (zh) * | 2018-05-31 | 2019-12-10 | 中国科学院大连化学物理研究所 | 一种铱/手性双膦体系催化亚胺不对称氢化方法 |
WO2021083018A1 (zh) * | 2019-10-30 | 2021-05-06 | 浙江九洲药业股份有限公司 | 吡啶环上3-位取代手性螺环胺基膦配体制备方法及其应用 |
CN111099986A (zh) * | 2019-12-13 | 2020-05-05 | 郑州大学 | 氢化反应方法 |
Non-Patent Citations (1)
Title |
---|
ESBEN P. K. OLSEN等: "Experimental and Theoretical Mechanistic Investigation of the Iridium-Catalyzed Dehydrogenative Decarbonylation of Primary Alcohols", 《J. AM. CHEM. SOC.》, pages 834 * |
Also Published As
Publication number | Publication date |
---|---|
CN114669333B (zh) | 2023-06-23 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Kwong et al. | Chiral pyridine-containing ligands in asymmetric catalysis | |
He et al. | Heterogeneous copper-free Sonogashira coupling reaction catalyzed by a reusable palladium Schiff base complex in water | |
Naghipour et al. | A highly active two six-membered phosphinite palladium PCP pincer complex [PdCl {C6H3 (CH2OPPri) 2-2, 6}] | |
Coşkun et al. | An efficient catalytic method for fulvene synthesis | |
CN108525704A (zh) | 用于烯烃氢甲酰化反应的催化剂及其制备方法和应用 | |
Aydemir et al. | Aminophosphine–palladium (II) complexes: Synthsesis, structure and applications in Suzuki and Heck cross-coupling reactions | |
CN110483252B (zh) | 一种不对称三芳基甲烷衍生物的合成方法 | |
WO2011040434A1 (ja) | シクロパラ(ヘテロ)アリーレン化合物およびその製造方法 | |
Duan et al. | Synthesis of new alkoxy/sulfonate-substituted carbene precursors derived from [2.2] paracyclophane and their application in the asymmetric arylation of aldehydes | |
Arena et al. | Structural control in palladium (II)-catalyzed enantioselective allylic alkylation by new chiral phosphine-phosphite and pyridine-phosphite ligands | |
CN105384731A (zh) | 一种手性含胺甲基吡啶噁唑啉的化合物及其制备方法 | |
Botteghi et al. | New synthetic route to pheniramines via hydroformylation of functionalyzed olefins | |
Majumder et al. | Bimetallic Pd II complexes with NHC/Py/PCy 3 donor set ligands: applications in α-arylation, Suzuki–Miyaura and Sonogashira coupling reactions | |
CN114669333A (zh) | 一种催化α-季碳醛脱羰氢化的催化剂体系和催化方法 | |
Šebesta et al. | Asymmetric allylic substitutions on symmetrical and non-symmetrical substrates using [5] ferrocenophane ligands | |
Samec et al. | Ruthenium carbene complexes bearing an anionic carboxylate chelated to a hemilabile ligand | |
CN110615811B (zh) | 一种手性亚磺酰胺单膦配体的大量制备方法 | |
Wang et al. | Copper-and base-free Sonogashira-type cross-coupling reaction of triarylantimony dicarboxylates with terminal alkynes under an aerobic condition | |
CN110117237B (zh) | 一种芳香腈或烯基腈类化合物的制备方法 | |
CN105669746A (zh) | 一种二芳基磷酸酯类化合物的合成方法 | |
Kajanus et al. | Synthesis of bis (phenylethynyl) arylene-linked diporphyrins designed for studies of intramolecular energy transfer | |
CN107266283A (zh) | 一种含有非端基双键的化合物的制备方法 | |
CN112851708B (zh) | 催化端炔或端位共轭烯炔制备烯醛的方法及其使用的双膦配体 | |
Chang et al. | Imidazolio-substituted secondary phosphine oxides as potential carbene reagents | |
Lee et al. | Formate as a CO surrogate for cascade processes: Rh-catalyzed cooperative decarbonylation and asymmetric Pauson–Khand-type cyclization reactions |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |