CN111995643B - Pentacyclic benzo-delta-phosphine lactam compound and preparation method thereof - Google Patents
Pentacyclic benzo-delta-phosphine lactam compound and preparation method thereof Download PDFInfo
- Publication number
- CN111995643B CN111995643B CN202010836230.7A CN202010836230A CN111995643B CN 111995643 B CN111995643 B CN 111995643B CN 202010836230 A CN202010836230 A CN 202010836230A CN 111995643 B CN111995643 B CN 111995643B
- Authority
- CN
- China
- Prior art keywords
- benzo
- group
- phosphine
- cdcl
- nmr
- 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.)
- Active
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- 229910000073 phosphorus hydride Inorganic materials 0.000 title claims abstract description 18
- 125000003118 aryl group Chemical group 0.000 claims abstract description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 14
- 150000001875 compounds Chemical class 0.000 claims abstract description 13
- UZVGSSNIUNSOFA-UHFFFAOYSA-N dibenzofuran-1-carboxylic acid Chemical compound O1C2=CC=CC=C2C2=C1C=CC=C2C(=O)O UZVGSSNIUNSOFA-UHFFFAOYSA-N 0.000 claims abstract description 10
- YCWSUKQGVSGXJO-NTUHNPAUSA-N nifuroxazide Chemical group C1=CC(O)=CC=C1C(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 YCWSUKQGVSGXJO-NTUHNPAUSA-N 0.000 claims abstract description 10
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 9
- 239000001301 oxygen Substances 0.000 claims abstract description 9
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 claims abstract description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 7
- 238000010438 heat treatment Methods 0.000 claims abstract description 6
- PFRUBEOIWWEFOL-UHFFFAOYSA-N [N].[S] Chemical compound [N].[S] PFRUBEOIWWEFOL-UHFFFAOYSA-N 0.000 claims abstract 2
- -1 phosphine oxide compound Chemical class 0.000 claims description 171
- 238000000034 method Methods 0.000 claims description 21
- 238000006243 chemical reaction Methods 0.000 claims description 19
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 125000004104 aryloxy group Chemical group 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 239000011737 fluorine Substances 0.000 claims description 5
- FYGHSUNMUKGBRK-UHFFFAOYSA-N 1,2,3-trimethylbenzene Chemical compound CC1=CC=CC(C)=C1C FYGHSUNMUKGBRK-UHFFFAOYSA-N 0.000 claims description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- HHVIBTZHLRERCL-UHFFFAOYSA-N sulfonyldimethane Chemical compound CS(C)(=O)=O HHVIBTZHLRERCL-UHFFFAOYSA-N 0.000 claims description 3
- RELMFMZEBKVZJC-UHFFFAOYSA-N 1,2,3-trichlorobenzene Chemical compound ClC1=CC=CC(Cl)=C1Cl RELMFMZEBKVZJC-UHFFFAOYSA-N 0.000 claims description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 claims description 2
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- RFFFKMOABOFIDF-UHFFFAOYSA-N Pentanenitrile Chemical compound CCCCC#N RFFFKMOABOFIDF-UHFFFAOYSA-N 0.000 claims description 2
- CYTYCFOTNPOANT-UHFFFAOYSA-N Perchloroethylene Chemical group ClC(Cl)=C(Cl)Cl CYTYCFOTNPOANT-UHFFFAOYSA-N 0.000 claims description 2
- KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical compound CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 claims description 2
- 229940117389 dichlorobenzene Drugs 0.000 claims description 2
- 238000005485 electric heating Methods 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 claims description 2
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- 229950011008 tetrachloroethylene Drugs 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- 239000002994 raw material Substances 0.000 abstract description 30
- 229940079593 drug Drugs 0.000 abstract description 10
- 239000003814 drug Substances 0.000 abstract description 10
- 239000000575 pesticide Substances 0.000 abstract description 7
- 239000011368 organic material Substances 0.000 abstract description 6
- 239000000543 intermediate Substances 0.000 abstract description 5
- MPQXHAGKBWFSNV-UHFFFAOYSA-N oxidophosphanium Chemical class [PH3]=O MPQXHAGKBWFSNV-UHFFFAOYSA-N 0.000 abstract description 4
- 230000002194 synthesizing effect Effects 0.000 abstract description 4
- 239000000463 material Substances 0.000 abstract description 3
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 abstract 4
- CCGKOQOJPYTBIH-UHFFFAOYSA-N ethenone Chemical compound C=C=O CCGKOQOJPYTBIH-UHFFFAOYSA-N 0.000 abstract 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 160
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 87
- 125000005605 benzo group Chemical group 0.000 description 62
- WXLCDTBTIVJDCE-UHFFFAOYSA-N 1,4-oxazepine Chemical compound O1C=CC=NC=C1 WXLCDTBTIVJDCE-UHFFFAOYSA-N 0.000 description 55
- 125000000623 heterocyclic group Chemical group 0.000 description 29
- 239000013078 crystal Substances 0.000 description 27
- 238000004679 31P NMR spectroscopy Methods 0.000 description 26
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 25
- 238000005160 1H NMR spectroscopy Methods 0.000 description 25
- 229910052799 carbon Inorganic materials 0.000 description 23
- SFJGCXYXEFWEBK-UHFFFAOYSA-N oxazepine Chemical compound O1C=CC=CC=N1 SFJGCXYXEFWEBK-UHFFFAOYSA-N 0.000 description 19
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 10
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 10
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- NYERMPLPURRVGM-UHFFFAOYSA-N thiazepine Chemical compound S1C=CC=CC=N1 NYERMPLPURRVGM-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 5
- QPPOMEOQNLTFRU-UHFFFAOYSA-N 1,4-thiazepine Chemical compound S1C=CC=NC=C1 QPPOMEOQNLTFRU-UHFFFAOYSA-N 0.000 description 4
- 238000004293 19F NMR spectroscopy Methods 0.000 description 4
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 4
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 4
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 4
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 3
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 125000001209 o-nitrophenyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])[N+]([O-])=O 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- NPUACKRELIJTFM-UHFFFAOYSA-N cr gas Chemical compound C1=NC2=CC=CC=C2OC2=CC=CC=C21 NPUACKRELIJTFM-UHFFFAOYSA-N 0.000 description 2
- RWGFKTVRMDUZSP-UHFFFAOYSA-N cumene Chemical compound CC(C)C1=CC=CC=C1 RWGFKTVRMDUZSP-UHFFFAOYSA-N 0.000 description 2
- 125000005921 isopentoxy group Chemical group 0.000 description 2
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 2
- 125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 150000004912 thiazepines Chemical class 0.000 description 2
- HVLLSGMXQDNUAL-UHFFFAOYSA-N triphenyl phosphite Chemical compound C=1C=CC=CC=1OP(OC=1C=CC=CC=1)OC1=CC=CC=C1 HVLLSGMXQDNUAL-UHFFFAOYSA-N 0.000 description 2
- 229940082496 Adrenoreceptor antagonist Drugs 0.000 description 1
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 1
- 150000001345 alkine derivatives Chemical group 0.000 description 1
- 150000001361 allenes Chemical group 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940127088 antihypertensive drug Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 150000005840 aryl radicals Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 239000002834 estrogen receptor modulator Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 description 1
- 125000005484 neopentoxy group Chemical group 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229910017464 nitrogen compound Inorganic materials 0.000 description 1
- 150000002830 nitrogen compounds Chemical class 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- IVMHDOBGNQOUHO-UHFFFAOYSA-N oxathiane Chemical class C1CCSOC1 IVMHDOBGNQOUHO-UHFFFAOYSA-N 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- ACVYVLVWPXVTIT-UHFFFAOYSA-M phosphinate Chemical compound [O-][PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-M 0.000 description 1
- UNQNIRQQBJCMQR-UHFFFAOYSA-N phosphorine Chemical compound C1=CC=PC=C1 UNQNIRQQBJCMQR-UHFFFAOYSA-N 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 239000010453 quartz Substances 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 125000005920 sec-butoxy group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000009281 ultraviolet germicidal irradiation Methods 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
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
- C07F9/6581—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms
- C07F9/6584—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms having one phosphorus atom as ring hetero atom
- C07F9/65842—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring
- C07F9/65846—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring the phosphorus atom being part of a six-membered ring which may be condensed with another ring system
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1003—Carbocyclic compounds
- C09K2211/1007—Non-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1018—Heterocyclic compounds
- C09K2211/1025—Heterocyclic compounds characterised by ligands
- C09K2211/1029—Heterocyclic compounds characterised by ligands containing one nitrogen atom as the heteroatom
- C09K2211/104—Heterocyclic compounds characterised by ligands containing one nitrogen atom as the heteroatom with other heteroatoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a pentacyclic fused benzo-delta-phosphine lactam compound and a preparation method thereof. Under the heating condition, diazo (aryl) methyl (diaryl) phosphine oxide compounds are rearranged into diaryl (aryl) phosphine ketene by wolff, and the diaryl (aryl) phosphine ketene reacts with dibenzo [ b, f ] [1,4] oxygen or sulfur nitrogen hetero-compounds to obtain pentacyclic benzo-delta-phosphine lactam compounds. The preparation method has the advantages of simple and easily obtained raw materials and convenient operation. The obtained compound can be applied to important organic materials, medicines and pesticides, can also be used for synthesizing intermediates of the organic materials and the medicines, and is used for preparing various materials and medicines.
Description
Technical Field
The invention belongs to the technical field of organic chemistry and organic synthesis, and particularly relates to a pentacyclic benzo-delta-phosphine lactam compound and a preparation method thereof.
Background
The benzo-delta-phosphine lactam compound is a very important organic synthesis intermediate and a compound with wide application in the fields of pharmaceutical chemistry, pesticides and synthetic chemistry. In medicinal chemistry, benzo [ b ] [1,4] oxathiane derivatives exhibit many biological activities, such as antioxidants, antihypertensive drugs, estrogen receptor modulators, adrenoreceptor antagonists, anticancer drugs and sweeteners (basoli, a.; Merlini, l.; Morini, g.; Vedani, angelo.j.chem.soc., Perkin trans.21998, 1449; Viglianisi, c.; menitti, s.curr.med.chem.2010,17,915.).
Since benzo-delta-phosphinolactams have important applications, different preparation methods have been developed successively. Benzo-delta-phosphinolactams may be arylated by palladium catalyzed C-H bonds (Lin, z. -q.; Wang, w. -z.; Yan, s. -b.; Duan, w. -l.angelw.chem.int.ed.2015, 54,6265; Guan, j.; Wu, g. -j.; Han, f. -s.chem.eur.j.2014,20,3301; Liu, l.t.; Zhang, a. -a.wang, y.f.; Zhang, f.q.; Zuo, z.z.; Zhao, w. -x.; fen, C. -l.; Ma, w.j.org.lett 2015,17,2046.), cobalt catalyzed phosphinate sp2Functionalization of C-H bonds with terminal alkynes or allenes (Nguyen, t.t.; Grigorjeva, l.; daugaulis, o.acs cat.2016, 6, 551; Yao, x.; Jin, l.; Rao, y.asian.j.org.chem.2017,6,825.), cyclization of triphenyl phosphite with ortho-alkynyl aniline (von negfut, c.l.; Shonkwiler, a.m.; Khalifa, m.m.; Zakharov, l.n.; Johnson, d.w.; Haley, m.angew.m.int.ed.2015, 54,13318.), and intramolecular aryl radical oxidative phosphinine amidation;han, f. -s.chem.commun.2017,53,5826; ma, y. -n.; zhang, x.; yang, s. -d.chem.eur.j.2017,23,3007; ma, y. -n.; cheng, M. -X.; yang, s. -d.org.lett.2017,19, 600.). However, these preparation methods often require noble metal catalysts or substrates with limited applicability, which are difficult to synthesize polycyclic fused benzo- δ -phosphinolactams.
The pentacyclic benzo-delta-phosphino lactam compound is obtained by reacting diazo (aryl) methyl (diaryl) phosphine oxide compounds with dibenzo [ b, f ] [1,4] oxygen or thiazepine compounds. The reaction raw materials are simple and easy to obtain, and the process is easy to operate. The obtained compound can be applied to important organic materials, medicines and pesticides, can also be used for synthesizing intermediates of the organic materials and the medicines, and is used for preparing various materials and medicines.
Disclosure of Invention
The invention aims to provide a pentacyclic benzo-delta-phosphine lactam compound and a preparation method thereof. The compounds can be applied to important organic materials, medicines and pesticides, can also be used for synthesizing intermediates of the organic materials, the medicines and the pesticides, and can be used for preparing various materials, the medicines and the pesticides. The preparation method of the compound adopts diazo (aryl) methyl (diaryl) phosphine oxide compounds and dibenzo [ b, f ] [1,4] oxygen or sulfur nitrogen hetero compounds as raw materials, the raw materials are simple and easy to obtain, and complicated operation is not needed, so that the preparation method is a simple and convenient method suitable for mass preparation.
The structure and the technical scheme of the compound are as follows:
pentacyclic benzo-delta-phosphinolactam compounds (formula 1) obtained by reacting diazo (aryl) methyl (diaryl) phosphinoxide compounds (formula 2) with dibenzo [ b, f ] [1,4] oxy or thiazepine compounds (formula 3).
In the above reaction formula:
x may be an oxygen or sulfur atom; r1、R2、R3And R4Is shown as havingAlkyl or alkoxy of 1 to 5 carbon atoms, aryl or aryloxy of 6 to 8 carbon atoms, fluorine, chlorine, bromine, cyano, nitro; r1、R2、R3And R4May be the same or different; the aryl and aryloxy groups may be alkyl or alkoxy groups having 1 to 3 carbon atoms, fluorine, chlorine, bromine, cyano, nitro, phenyl and phenoxy groups; r3/4And R4/3Represents a substituent R3The other is R4。
Wherein the alkyl refers to a straight chain or branched chain alkyl group having 1 to 5 carbon atoms, such as: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, pentyl, isopentyl, sec-pentyl, neopentyl, particularly preferably a linear or branched alkyl group having 1 to 3 carbon atoms, most preferably methyl and ethyl.
The alkoxy refers to a straight chain or branched chain alkoxy with 1-5 carbon atoms, such as: methoxy group, ethoxy group, propoxy group, isopropoxy group, butoxy group, isobutoxy group, tert-butoxy group, sec-butoxy group, pentyloxy group, isopentyloxy group, sec-pentyloxy group, neopentyloxy group, particularly preferably straight-chain or branched alkoxy group having 1 to 3 carbon atoms, most preferably methoxy group and ethoxy group.
The aryl refers to aryl with 6-8 carbon atoms. Preferably, it is phenyl, o-methylphenyl, m-methylphenyl, p-methylphenyl, o-ethylphenyl, m-ethylphenyl, p-ethylphenyl, 2, 3-dimethylphenyl, 2, 4-dimethylphenyl, 2, 5-dimethylphenyl, 2, 6-dimethylphenyl, 3, 4-dimethylphenyl, 3, 5-dimethylphenyl, o-methoxyphenyl, m-methoxyphenyl, p-methoxyphenyl, o-ethoxyphenyl, m-ethoxyphenyl, p-ethoxyphenyl, 2, 3-methyleneoxyphenyl, 3, 4-methyleneoxyphenyl, o-fluorophenyl, m-fluorophenyl, p-fluorophenyl, o-chlorophenyl, m-chlorophenyl, p-chlorophenyl, o-nitrophenyl, m-nitrophenyl, p-nitrophenyl, o-cyanophenyl, m-cyanophenyl, p-cyanophenyl, etc.
The aryloxy group refers to an aryloxy group having 6 to 8 carbon atoms. Preferably phenoxy, o-methylphenoxy, m-methylphenoxy, p-methylphenoxy, o-ethylphenoxy, m-ethylphenoxy, p-ethylphenoxy, 2, 3-dimethylphenoxy, 2, 4-dimethylphenoxy, 2, 5-dimethylphenoxy, 2, 6-dimethylphenoxy, 3, 4-dimethylphenoxy, 3, 5-dimethylphenoxy, o-methoxyphenoxy, m-methoxyphenoxy, p-methoxyphenoxy, o-ethoxyphenoxy, m-ethoxyphenoxy, p-ethoxyphenoxy, 2, 3-methyleneoxyphenoxy, 3, 4-methyleneoxyphenoxy, o-fluorophenoxy, m-fluorophenoxy, p-fluorophenoxy, o-chlorophenoxy, m-chlorophenoxy, p-chlorophenoxy, o-nitrophenoxy, m-nitrophenoxy, p-nitrophenoxy, o-ethylphenoxy, m-ethylphenoxy, p-methoxyphenoxy, p-ethoxyphenoxy, o-ethoxyphenoxy, m-phenoxy, m-methoxyphenoxy, p-ethoxyphenoxy, p-methoxyphenoxy, p-fluorophenoxy, p-propxy, p-fluorophenoxy, p-propxy, p-fluorophenoxy, p-propxy, p-fluorophenoxy, p-fluorop, O-cyanophenoxy, m-cyanophenoxy, p-cyanophenoxy and the like.
Preferred R1、R2、R3And R4Represents methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, pentyl, isopentyl, sec-pentyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy, sec-butoxy, pentyloxy, isopentyloxy, sec-pentyloxy, phenyl, o-methylphenyl, m-methylphenyl, p-methylphenyl, o-ethylphenyl, m-ethylphenyl, p-ethylphenyl, 2, 3-dimethylphenyl, 2, 4-dimethylphenyl, 2, 5-dimethylphenyl, 2, 6-dimethylphenyl, 3, 4-dimethylphenyl, 3, 5-dimethylphenyl, o-methoxyphenyl, m-methoxyphenyl, p-methoxyphenyl, 2, 3-methyleneoxyphenyl, 3, 4-methyleneoxyphenyl, o-fluorophenyl, m-fluorophenyl, o-fluorophenyl, isopentyl, methyl, phenyl, o-methylphenyl, n-ethylphenyl, o-ethylphenyl, p-ethylphenyl, o-ethylphenyl, p-ethylphenyl, 2, 3-methyleneoxyphenyl, 3, 4-methyleneoxyphenyl, o-fluorophenyl, m-fluorophenyl, o-ethylphenyl, or, P-fluorophenyl group, o-chlorophenyl group, m-chlorophenyl group, p-chlorophenyl group, o-nitrophenyl group, m-nitrophenyl group, p-nitrophenyl group, o-cyanophenyl group, m-cyanophenyl group, p-cyanophenyl group, phenoxy group, o-methylphenoxy group, m-methylphenoxy group, p-methylphenoxy group, 2, 3-dimethylphenoxy group, 2, 4-dimethylphenoxy group, 2, 5-dimethylphenoxy group, 2, 6-dimethylphenoxy group, 3, 4-dimethylphenoxy group, 3, 5-dimethylphenoxy group, o-methoxyphenoxy group, m-methoxyphenoxy group, p-methoxyphenoxy group, 2, 3-methyleneoxyphenoxy group, 3, 4-methyleneoxyphenoxy group, o-fluorophenoxy group, m-fluorophenoxy group, p-fluorophenoxy group, o-chlorobenzoxy groupOxy, m-chlorophenoxy, p-chlorophenoxy, o-nitrophenoxy, m-nitrophenoxy, p-nitrophenoxy, o-cyanophenoxy, m-cyanophenoxy, p-cyanophenoxy, fluorine, chlorine, bromine, cyano, nitro, more preferably methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, isopentyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, isopentyloxy, phenyl, o-methylphenyl, m-methylphenyl, p-methylphenyl, 2, 3-dimethylphenyl, 2, 4-dimethylphenyl, 2, 5-dimethylphenyl, 2, 6-dimethylphenyl, 3, 4-dimethylphenyl, 3, 5-dimethylphenyl, o-methoxyphenyl, m-methoxyphenyl, p-methoxyphenyl, 2, 3-methyleneoxyphenyl, o-cyanophenoxy, m-phenoxy, m-cyanophenoxy, m-phenoxy, n, m-cyanophenoxy, n, butoxy, iso-isobutoxy, iso-butoxy, phenyl, o-butoxy, o-phenoxy, o-methoxy, o-methyl, o-methyl-phenyl, o-methyl, o-methyl, o-methyl-phenyl, o-methyl, o-phenyl, o-methyl, o-methyl, o-methyl, o-methyl-phenyl, o-methyl, o-methyl-, 3, 4-methyleneoxyphenyl, o-fluorophenyl, m-fluorophenyl, p-fluorophenyl, o-chlorophenyl, m-chlorophenyl, p-chlorophenyl, o-nitrophenyl, m-nitrophenyl, p-nitrophenyl, o-cyanophenyl, m-cyanophenyl, p-cyanophenyl, phenoxy, o-methylphenoxy, m-methylphenoxy, p-methylphenoxy, 2, 3-dimethylphenoxy, 2, 4-dimethylphenoxy, 2, 5-dimethylphenoxy, 2, 6-dimethylphenoxy, 3, 4-dimethylphenoxy, 3, 5-dimethylphenoxy, o-methoxyphenoxy, m-methoxyphenoxy, p-methoxyphenoxy, 2, 3-methyleneoxyphenoxy, 3, 4-methyleneoxyphenoxy, o-fluorophenoxy, m-fluorophenoxy, p-fluorophenoxy, o-chlorophenoxy, p-chlorophenoxy, o-methyl, p-methyl-2, 4-dimethylphenoxy, 2, 4-methylphenoxy, p-methylphenoxy, o, p-fluorophenoxy, p-chlorophenoxy, p-methyl, p-chlorophenoxy, p-o, p-chlorophenoxy, p, M-chlorophenoxy group, p-chlorophenoxy group, o-nitrophenoxy group, m-nitrophenoxy group, p-nitrophenoxy group, o-cyanophenoxy group, m-cyanophenoxy group, fluorine, chlorine, bromine, cyano group, nitro group, most preferably methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, pentyl group, isopentyl group, methoxy group, ethoxy group, propoxy group, isopropoxy group, pentyloxy group, isopentyloxy group, phenyl group, o-methylphenyl group, m-methylphenyl group, p-methylphenyl group, o-methoxyphenyl group, m-methoxyphenyl group, p-methoxyphenyl group, 2, 3-methyleneoxyphenyl group, 3, 4-methyleneoxyphenyl group, o-fluorophenyl group, m-fluorophenyl group, p-fluorophenyl group, o-chlorophenyl group, m-chlorophenyl group, p-nitrophenyl group, o-cyanophenyl group, m-cyanophenyl groupA group, p-cyanophenyl group, phenoxy group, o-methylphenoxy group, m-methylphenoxy group, p-methylphenoxy group, o-methoxyphenoxy group, m-methoxyphenoxy group, p-methoxyphenoxy group, 2, 3-methyleneoxyphenoxy group, 3, 4-methyleneoxyphenoxy group, o-fluorophenoxy group, m-fluorophenoxy group, p-fluorophenoxy group, o-chlorophenoxy group, m-chlorophenoxy group, p-chlorophenoxy group, fluorine, chlorine, bromine, cyano group, nitro group.
The prepared pentacyclic benzo-delta-phosphine lactam compound comprises the following thirty compounds 1a to 1':
(R1、R2、R3and R4The position numbers of the substituents are the numbers thereof in the structure of formula 1)
1a：X＝O,R1＝R2＝R3＝R4＝H；
1b：X＝O,R2＝11-Me,R1＝R3＝R4＝H；
1c：X＝O,R2＝11-Cl,R1＝R3＝R4＝H；
1d：X＝O,R2＝12-Me,R1＝R3＝R4＝H；
1e：X＝O,R2＝12-F,R1＝R3＝R4＝H；
1f：X＝O,R2＝12-Cl,R1＝R3＝R4＝H；
1g：X＝O,R2＝12-Br,R1＝R3＝R4＝H；
1h：X＝O,R2＝12-MeO,R1＝R3＝R4＝H；
1i：X＝O,R1＝7-Me,R2＝R3＝R4＝H；
1j：X＝O,R1＝7-Cl,R2＝R3＝R4＝H；
1k：X＝O,R1＝6-NO2,R2＝R3＝R4＝H；
1l：X＝O,R2＝11-NO2,R1＝R3＝R4＝H；
1m：X＝O,R1＝7-Cl,R2＝11-Cl,R3＝R4＝H；
1n：X＝O,R1＝7-Me,R2＝11-Me,R3＝R4＝H；
1o：X＝S,R1＝R2＝R3＝R4＝H；
1p：X＝S,R1＝7-Me,R2＝R3＝R4＝H；
1q：X＝S,R1＝8-F,R2＝R3＝R4＝H；
1r：X＝S,R1＝H,R2＝12-Cl,R3＝R4＝H；
1s：X＝O,R1＝H,R2＝11-Me,R3＝H,R4＝16-(2-F)；
1t：X＝O,R1＝H,R2＝11-Cl,R3＝H,R4＝16-(2-F)；
1u：X＝O,R1＝H,R2＝11-Me,R3＝He,R4＝16-(4-Me)；
1’u：X＝O,R1＝H,R2＝11-Me,R3＝3-Me,R4＝H；
1v：X＝O,R1＝H,R2＝11-Me,R3＝He,R4＝16-(4-Cl)；
1’v：X＝O,R1＝H,R2＝11-Me,R3＝3-Cl,R4＝H；
1w：X＝O,R1＝H,R2＝11-Me,R3＝H,R4＝15,16-(4-Me)2；
1’w：X＝O,R1＝H,R2＝11-Me,R3＝3-Me,R4＝15-(4-Me)；
1x：X＝O,R1＝H,R2＝11-Me,R3＝H,R4＝15,16-(4-Cl)2；
1’x：X＝O,R1＝H,R2＝11-Me,R3＝3-Cl,R4＝15-(4-Cl)；
1y：X＝O,R1＝H,R2＝11-Cl,R3＝H,R4＝15,16-(4-Cl)2；
1’y：X＝O,R1＝H,R2＝11-Cl,R3＝3-Cl,R4＝15-(4-Cl).
The above-mentioned preparation method is usually to obtain pentacyclic benzo-delta-phosphinolactam compound by reaction of diazo (aryl) methyl (diaryl) phosphine oxide compound with dibenzo [ b, f ] [1,4] oxygen or thiazepine compound in solvent.
In the preparation method, the raw materials of the diazo (aryl) methyl (diaryl) phosphine oxide compound and the dibenzo [ b, f ] [1,4] oxygen or sulfur nitrogen hetero compound can be directly prepared according to a literature method.
In the above-mentioned production process, a solvent usually used is dimethyl sulfoxide, cyclobutane sulfoxide, dimethyl sulfone, sulfolane, acetonitrile, propionitrile, butyronitrile, valeronitrile, chloroform, 1, 2-dichloroethane, tetrachloroethylene, tetrahydrofuran, 1, 4-dioxane, ethylene glycol dimethyl ether, benzene, toluene, xylene, trimethylbenzene, ethylbenzene, cumene, chlorobenzene, dichlorobenzene, trichlorobenzene or a mixture thereof.
The preparation method uses the reaction temperature of 20-150 ℃, and the reaction can be carried out by adopting the traditional steam heating, electric heating and microwave heating.
The preparation method uses the reaction temperature of-40-150 ℃, and the reaction can be carried out by illumination.
The preparation method uses the reaction condition that the reaction is carried out in an anhydrous solvent under the protection of nitrogen.
The invention has the advantages and positive effects that:
the pentacyclic benzo-delta-phosphine lactam compound prepared by the invention is a very important organic intermediate, has wide application in the fields of medicines, pesticide chemistry and synthetic chemistry, and also shows various biological activities, fluorescence properties and the like.
The compound and the preparation method thereof provided by the invention take simple and easily obtained diazo (aryl) methyl (diaryl) phosphine oxide compounds and dibenzo [ b, f ] [1,4] oxygen or sulfur-nitrogen-doped nitrogen compounds as raw materials, and the compound can be prepared according to a known method. The method is simple to operate, has a short synthetic route, can be used for synthesizing pentacyclic benzo-delta-phosphine lactam compounds containing structural diversity, is suitable for large-scale preparation, and has very important significance for the preparation and application of the compounds.
Detailed Description
The invention is further illustrated by the following examples, which are not to be construed as limiting the invention thereto.
Example one
Rel- (4bS,15S,16S) -15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f ] benzo [4,5] [1,2] azophosp-cyclohexa [1,6-d ] [1,4] oxazepine 15-oxide 1a
Azo (phenyl) (diphenyl) phosphine oxide (0.4mmol,127mg) and dibenzo [ b, f ]][1,4]Oxazepine (0.2mmol,39mg) was added to a 10mL microwave reaction tube and 3mL anhydrous chlorobenzene was added and the reaction was stirred in a microwave reactor at 160 ℃ under nitrogen protection for 10 minutes under microwave radiation. Cooling, distilling off solvent, separating residue with silica gel column, and gradient eluting with petroleum ether and ethyl acetate (5:1 to 1: 1) to obtain colorless crystals 82mg, 84%; mp.286-288 deg.C, IR (KBr) v (cm)-1)3057,2924,2851,1599,1492,1258,1243,1210,1116,1049,1017,978,784,751,693.1H NMR(400MHz,CDCl3)δ7.77(dd,J＝7.0,1.9Hz,1H),7.45–7.32(m,3H),7.27–7.02(m,13H),6.80–6.62(m,5H),6.34(d,J＝7.8Hz,1H),5.12(d,J＝28.6Hz,1H).13C NMR(101MHz,CDCl3)δ159.5,153.4(d,J＝4.9Hz),140.4(d,J＝3.8Hz),134.5(d,J＝3.0Hz),134.3(d,J＝5.1Hz),133.5(d,J＝9.0Hz),131.9(d,J＝2.0Hz),131.8(d,J＝4.1Hz),131.3(d,J＝5.3Hz),130.7,128.5(d,J＝153.8Hz),128.2,127.9(d,J＝7.8Hz),127.8,127.5,126.9,126.1(d,J＝2.9Hz),126.0,125.6,125.3,125.0,121.0,120.6,62.1(d,J＝2.6Hz),51.4(d,J＝78.6Hz).31P NMR(162MHz,CDCl3)δ28.6。
Example two
Rel- (4bS,15S,16S) -15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f ] benzo [4,5] [1,2] azophosp-hoxano [1,6-d ] [1,4] oxazepine 15-oxide 1a
Azo (phenyl) (diphenyl) phosphine oxide (0.4mmol,127mg) and dibenzo [ b, f ] [1,4] oxazepine (0.2mmol,39mg) were added to a 10mL test tube and 3mL of anhydrous chlorobenzene was added, and the reaction was stirred with heating at 160 ℃ for 1 hour under nitrogen. After cooling, the solvent was distilled off, and the residue was separated by means of a silica gel column and eluted with a gradient of petroleum ether and ethyl acetate (5:1 to 1: 1) to give 78mg, 80% as colorless crystals.
EXAMPLE III
Rel- (4bS,15S,16S) -15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f ] benzo [4,5] [1,2] azophosp-hoxano [1,6-d ] [1,4] oxazepine 15-oxide 1a
Azo (phenyl) (diphenyl) phosphine oxide (0.4mmol,127mg) and dibenzo [ b, f ] [1,4] oxazepine (0.2mmol,39mg) were added to a 10mL quartz reaction tube and 3mL anhydrous chlorobenzene was added and the reaction was stirred at room temperature for half an hour under UV irradiation. The solvent was distilled off, and the residue was separated by means of a silica gel column and eluted with a gradient of petroleum ether and ethyl acetate (5:1 to 1: 1) to give 73mg, 75% as colorless crystals.
Example four
Rel- (4bS,15S,16S) -11-methyl-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f ] benzo [4,5] [1,2] azophosp-hoxano [1,6-d ] [1,4] oxazepine 15-oxide 1b
Following the procedure described in example one, 7-methyldibenzo [ b, f ] was used][1,4]Taking oxazepine as a raw material to obtain Rel- (4bS,15S,16S) -11-methyl-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f)]Benzo [4,5]][1,2]N-P heterocyclic hexane [1,6-d ]][1,4]Oxazepine 15-oxide, colorless crystal, 96mg, 94%; mp.294-296 deg.C, IR (KBr) v (cm)-1)3060,2923,2854,1599,1502,1260,1212,1122,980,933,785,748,695.1H NMR(400MHz,CDCl3)δ7.65(d,J＝8.0Hz,1H),7.43–7.08(m,15H),6.86(d,J＝1.3Hz,1H),6.75–6.65(m,3H),6.56(dd,J＝8.2,1.4Hz,1H),6.30(d,J＝7.6Hz,1H),5.07(d,J＝28.2Hz,1H),2.08(s,3H).13C NMR(101MHz,CDCl3)δ159.5,153.3(d,J＝5.0Hz),140.4(d,J＝4.2Hz),135.2,134.3(d,J＝5.2Hz),133.6(d,J＝9.0Hz),132.0(d,J＝4.2Hz),131.9(d,J＝2.0Hz),131.8(d,J＝2.4Hz),131.3(d,J＝5.2Hz),131.6,130.6,128.7(d,J＝130.1Hz),128.1,128.0(d,J＝7.3Hz),127.8,127.5(d,J＝2.0Hz),126.9,126.2,125.9,125.5,121.2,121.1,62.3(d,J＝2.8Hz),51.5(d,J＝78.7Hz),20.6.31P NMR(162MHz,CDCl3)δ28.1。
EXAMPLE five
Rel- (4bS,15S,16S) -11-chloro-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f ] benzo [4,5] [1,2] azophosp-hoxano [1,6-d ] [1,4] oxazepine 15-oxide 1c
Using 7-chlorodibenzo [ b, f ] as described in example one][1,4]Taking oxazepine as a raw material to obtain Rel- (4bS,15S,16S) -11-chloro-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f)]Benzo [4,5]][1,2]N-P heterocyclic hexane [1,6-d ]][1,4]Oxazepine 15-oxide, colorless crystal, 100mg, 96%; mp.282-284 deg.C, IR (KBr) v (cm)-1)3062,2926,2854,1736,1598,1565,1485,1268,1198,1115,1020,975,902,782,740,701,574,528.1H NMR(400MHz,CDCl3)δ7.65(d,J＝8.8Hz,1H),7.40–7.34(m,1H),7.32–7.21(m,3H),7.19–7.10(m,4H),7.08–6.99(m,7H),6.97(d,J＝2.4Hz,1H),6.71–6.60(m,3H),6.59–6.52(m,1H),6.25(d,J＝8.0Hz,1H),5.05(d,J＝28.7Hz,1H).13C NMR(101MHz,CDCl3)δ159.2,153.7(d,J＝5.0Hz),140.3(d,J＝3.9Hz),134.2(d,J＝5.3Hz),133.4(d,J＝6.3Hz),133.4,132.2(d,J＝2.8Hz),131.8,131.44,131.35(d,J＝5.7Hz),131.0,129.2,128.24(d,J＝2.2Hz),128.20(d,J＝142.6Hz),128.1,127.7(d,J＝2.7Hz),127.4(d,J＝2.2Hz),127.4,127.0(d,J＝2.0Hz),126.7(d,J＝3.4Hz),126.0,125.8(d,J＝2.3Hz),125.4,121.2,121.0,62.0(d,J＝3.1Hz),51.4(d,J＝78.5Hz).31P NMR(162MHz,CDCl3)δ28.9。
EXAMPLE six
Rel- (4bS,15S,16S) -12-methyl-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f ] benzo [4,5] [1,2] azophosp-hoxano [1,6-d ] [1,4] oxazepine 15-oxide 1d
Using 8-methyldibenzo [ b, f ] as described in example one][1,4]Oxazepine is used as a raw material to obtainRel- (4bS,15S,16S) -12-methyl-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f)]Benzo [4,5]][1,2]N-P heterocyclic hexane [1,6-d ]][1,4]Oxazepine 15-oxide, colorless crystal, 88mg, 88%; mp.300-302 deg.C, IR (KBr) v (cm)-1)2972,2926,1508,1380,1266,1214,1089,1048,880,744.1H NMR(400MHz,CDCl3)δ7.56(s,1H),7.43–7.07(m,15H),6.91(d,J＝8.1Hz,1H),6.78–6.67(m,3H),6.55(d,J＝8.1Hz,1H),6.30(d,J＝7.7Hz,1H),5.08(d,J＝28.4Hz,1H).13C NMR(101MHz,CDCl3)δ159.6,151.3(d,J＝4.9Hz),140.3(d,J＝4.2Hz),135.1,134.3(d,J＝5.3Hz),134.1(d,J＝2.7Hz),133.5(d,J＝9.1Hz),131.9,131.3(d,J＝5.3Hz),131.1(d,J＝89.6Hz),128.6(d,J＝153.7Hz),128.1,128.0,127.9,127.7,127.5(d,J＝1.8Hz),126.9,126.6(d,J＝2.8Hz),126.2,125.5,121.0,120.2,62.2(d,J＝2.7Hz),51.5(d,J＝78.7Hz),20.6.31P NMR(162MHz,CDCl3)δ28.3。
EXAMPLE seven
Rel- (4bS,15S,16S) -12-fluoro-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f ] benzo [4,5] [1,2] azophosp-hoxano [1,6-d ] [1,4] oxazepine 15-oxide 1e
Using 8-fluorodibenzo [ b, f ] as described in example one][1,4]Taking oxazepine as a raw material to obtain Rel- (4bS,15S,16S) -12-fluoro-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f)]Benzo [4,5]][1,2]N-P heterocyclic hexane [1,6-d ]][1,4]Oxazepine 15-oxide, colorless crystals, 82mg, 81%; mp.310-312 deg.C, IR (KBr) v (cm)-1)3060,2925,2853,1736,1590,1517,1491,1340,1259,1243,1211,1113,974,745,700.1H NMR(400MHz,CDCl3)δ7.53(dd,J＝10.1,2.7Hz,1H),7.49–7.43(m,1H),7.41–7.09(m,14H),6.98(dd,J＝8.8,5.5Hz,1H),6.79(d,J＝7.1Hz,2H),6.65–6.60(m,1H),6.47–6.39(m,1H),6.34(d,J＝8.2Hz,1H),5.13(d,J＝29.0Hz,1H).13C NMR(101MHz,CDCl3)δ159.80,159.1(d,JC-F＝243.8Hz),149.7(dd,J＝4.9,3.1Hz),140.5(d,J＝3.6Hz),135.6(d,J＝3.3Hz),135.5(d,J＝3.3Hz),134.2(d,J＝5.1Hz),133.4(d,J＝9.0Hz),128.33(d,J＝2.0Hz),128.25(d,J＝128.2Hz),128.1,128.1(d,J＝0.6Hz),128.0,127.8(d,J＝2.7Hz),127.4(d,J＝6.6Hz),127.2(d,J＝6.8Hz),127.1(d,J＝1.8Hz),126.0,125.6(d,J＝2.1Hz),121.2(d,J＝9.8Hz),120.8,113.0(d,J＝23.0Hz),110.9(d,J＝23.2Hz),61.9(d,J＝3.1Hz),51.3(d,J＝78.3Hz).31P NMR(162MHz,CDCl3)δ29.1.19F NMR(376MHz,CDCl3)δ-115.7。
Example eight
Rel- (4bS,15S,16S) -12-chloro-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f ] benzo [4,5] [1,2] azophosp-hoxaneo [1,6-d ] [1,4] oxazepine 15-oxide 1f
Using 8-chlorodibenzo [ b, f ] as described in example one][1,4]Taking oxazepine as a raw material to obtain Rel- (4bS,15S,16S) -12-chloro-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f)]Benzo [4,5]][1,2]N-P heterocyclic hexane [1,6-d ]][1,4]Oxazepine 15-oxide, colorless crystal, 90mg, 87%; mp.320-322 deg.C, IR (KBr) v (cm)-1)3060,2926,2852,1598,1492,1241,1210,1111,1076,978,782,696.1H NMR(400MHz,CDCl3)δ7.77(d,J＝1.6Hz,1H),7.46–7.21(m,8H),7.18–7.09(m,7H),6.96(d,J＝8.4Hz,1H),6.78(d,J＝7.4Hz,2H),6.73–6.68(m,1H),6.68–6.63(m,1H),6.32(d,J＝8.0Hz,1H),5.12(d,J＝28.9Hz,1H).13C NMR(101MHz,CDCl3)δ159.3,152.0(d,J＝4.9Hz),140.2(d,J＝3.5Hz),135.6(d,J＝2.7Hz),134.2(d,J＝5.1Hz),133.4(d,J＝9.0Hz),132.3,131.8,131.4(d,J＝5.2Hz),131.0,130.2,128.3,128.22(d,J＝128.2Hz),128.15(d,J＝2.9Hz),128.0,127.7(d,J＝2.0Hz),127.5(d,J＝3.0Hz),127.1,126.0,125.8,125.8(d,J＝3.2Hz),124.7,121.5,120.9,62.0(d,J＝2.5Hz),51.4(d,J＝78.5Hz).31P NMR(162MHz,CDCl3)δ29.0。
Example nine
1g of Rel- (4bS,15S,16S) -12-bromo-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f ] benzo [4,5] [1,2] azophospino [1,6-d ] [1,4] oxazepine 15-oxide
Using 8-bromodibenzo [ b, f ] as described in example one][1,4]Taking oxazepine as a raw material to obtain Rel- (4bS,15S,16S) -12-bromo-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f)]Benzo [4,5]][1,2]N-P heterocyclic hexane [1,6-d ]][1,4]Oxazepine 15-oxide, colorless crystals, 94mg,83％；mp.330–332℃.IR(KBr)ν(cm-1)2974,2928,1619,1591,1483,1458,1326,1213,1089,1049,978,881,738,701.1H NMR(400MHz,CDCl3)δ7.90(d,J＝1.4Hz,1H),7.49–7.40(m,1H),7.39–7.11(m,14H),6.92–6.82(m,2H),6.78(d,J＝7.4Hz,2H),6.70–6.62(m,1H),6.31(d,J＝8.0Hz,1H),5.11(d,J＝28.9Hz,1H).13C NMR(101MHz,CDCl3)δ159.2,152.5(d,J＝4.9Hz),140.2(d,J＝3.8Hz),135.9(d,J＝2.9Hz),134.2(d,J＝5.2Hz),133.4(d,J＝9.1Hz),132.3,131.8(d,J＝2.0Hz),131.4(d,J＝5.4Hz),131.0,128.6(d,J＝3.1Hz),128.28,128.23(d,J＝128.2Hz),128.2(d,J＝4.5Hz),128.0,127.7,127.5(d,J＝6.8Hz),127.4,127.1,126.0(d,J＝12.7Hz),122.0,121.0,117.7,62.0(d,J＝2.4Hz),51.4(d,J＝78.5Hz).31P NMR(162MHz,CDCl3)δ29.0。
Example ten
Rel- (4bS,15S,16S) -12-methoxy-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f ] benzo [4,5] [1,2] azophosp-cyclohexo [1,6-d ] [1,4] oxazepine 15-oxide 1h
Using 8-methoxydibenzo [ b, f ] as described in example one][1,4]Taking oxazepine as a raw material to obtain Rel- (4bS,15S,16S) -12-methoxyl-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f)]Benzo [4,5]][1,2]N-P heterocyclic hexane [1,6-d ]][1,4]Oxazepine 15-oxide, colorless crystal, 73mg, 71%; mp.286-288 deg.C, IR (KBr) v (cm)-1)3060,2935,2834,1607,1492,1265,1215,1115,1053,986,810,781,751,701.1H NMR(400MHz,CDCl3)δ7.35–6.98(m,16H),6.85(d,J＝8.8Hz,1H),6.71(d,J＝7.2Hz,2H),6.59–6.52(m,1H),6.25(d,J＝8.0Hz,1H),6.20(dd,J＝8.8,2.8Hz,1H),5.04(d,J＝28.8Hz,1H),3.43(s,3H).13C NMR(101MHz,CDCl3)δ160.1,156.5,147.5(d,J＝4.9Hz),140.6(d,J＝3.9Hz),134.8(d,J＝2.4Hz),134.2(d,J＝5.0Hz),133.4(d,J＝9.1Hz),132.1(d,J＝2.8Hz),131.7,131.4(d,J＝5.3Hz),130.8,128.4(d,J＝171.6Hz),128.2,128.0(d,J＝3.4Hz),127.6(d,J＝3.0Hz),127.2(d,J＝6.7Hz),127.0,125.8,125.6,121.0,120.8,111.1,110.3(d,J＝3.5Hz),62.0(d,J＝2.6Hz),55.4,51.4(d,J＝78.2Hz).31P NMR(162MHz,CDCl3)δ28.8。
EXAMPLE eleven
Rel- (4bS,15S,16S) -7-methyl-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f ] benzo [4,5] [1,2] azophosp-xyazepino [1,6-d ] [1,4] oxazepine 15-oxide 1i
Using 3-methyldibenzo [ b, f ] as described in example one][1,4]Taking oxazepine as a raw material to obtain Rel- (4bS,15S,16S) -7-methyl-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f)]Benzo [4,5]][1,2]N-P heterocyclic hexane [1,6-d ]][1,4]Oxazepine 15-oxide, colorless crystal, 71mg, 72%; mp.296-298 deg.C, IR (KBr) v (cm)-1)3057,2925,2859,1598,1492,1244,1208,1112,982,781,746,701,693.1H NMR(400MHz,CDCl3)δ7.74(dd,J＝7.3,1.4Hz,1H),7.30–7.01(m,15H),6.80–6.67(m,5H),6.30(d,J＝8.0Hz,1H),5.10(d,J＝28.7Hz,1H),2.42(s,3H).13C NMR(101MHz,CDCl3)δ159.5,153.5(d,J＝5.0Hz),141.4,140.8(d,J＝3.8Hz),134.5(d,J＝3.4Hz),134.4(d,J＝5.2Hz),133.5(d,J＝9.0Hz),132.0(d,J＝2.9Hz),131.7(d,J＝4.2Hz),131.5,131.4,128.6(d,J＝129.2Hz),128.2(d,J＝2.0Hz),127.9(d,J＝2.2Hz),127.8,127.6(d,J＝2.8Hz),127.3(d,J＝6.7Hz),126.9(d,J＝1.7Hz),126.4,126.0(d,J＝3.4Hz),125.9(d,J＝2.0Hz),125.3,124.9,124.5(d,J＝6.7Hz),121.6,120.7,61.8(d,J＝3.1Hz),51.5(d,J＝78.6Hz),21.2.31P NMR(162MHz,CDCl3)δ28.7.
EXAMPLE twelve
Rel- (4bS,15S,16S) -7-chloro-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f ] benzo [4,5] [1,2] azophosp-hoxano [1,6-d ] [1,4] oxazepine 15-oxide 1j
Using 3-chlorodibenzo [ b, f ] as described in example one][1,4]Taking oxazepine as a raw material to obtain Rel- (4bS,15S,16S) -7-chloro-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f)]Benzo [4,5]][1,2]N-P heterocyclic hexane [1,6-d ]][1,4]Oxazepine 15-oxide, colorless crystal, 89mg, 86%; mp.302-304 deg.C, IR (KBr) v (cm)-1)3057,2924,2851,1599,1492,1258,1243,1210,1116,1049,1017,978,784,751,684.1H NMR(400MHz,CDCl3)δ7.79–7.72(m,1H),7.40(d,J＝2.0Hz,1H),7.30–7.03(m,14H),6.84–6.73(m,3H),6.70(d,J＝7.4Hz,2H),6.30(d,J＝7.6Hz,1H),5.08(d,J＝28.1Hz,1H).13C NMR(101MHz,CDCl3)δ159.4,152.9(d,J＝5.1Hz),139.6(d,J＝4.7Hz),135.4,134.5,134.2(d,J＝5.4Hz),133.5(d,J＝9.0Hz),132.4,132.1,131.9,131.2(d,J＝5.4Hz),128.31,128.29(d,J＝129.5Hz),128.1,127.9(d,J＝13.1Hz),127.6(d,J＝2.8Hz),127.1(d,J＝1.5Hz),126.6(d,J＝6.5Hz),125.7(d,J＝3.0Hz),125.4,61.9(d,J＝3.3Hz),51.5(d,J＝78.9Hz).31P NMR(162MHz,CDCl3)δ28.5。
EXAMPLE thirteen
Rel- (4bS,15S,16S) -6-nitro-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f ] benzo [4,5] [1,2] azophosp-hoxano [1,6-d ] [1,4] oxazepine 15-oxide 1k
Following the procedure described in example one, 2-nitrodibenzo [ b, f ]][1,4]Taking oxazepine as a raw material to obtain Rel- (4bS,15S,16S) -6-nitro-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f)]Benzo [4,5]][1,2]N-P heterocyclic hexane [1,6-d ]][1,4]Oxazepine 15-oxide, colorless crystals, 50mg, 47%); mp.303-305 deg.C, IR (KBr) v (cm)-1)3059,2925,2852,1527,1492,1439,1347,1243,1114,980,750.1H NMR(400MHz,CDCl3)δ8.30–8.20(m,2H),7.84–7.79(m,1H),7.45–7.23(m,8H),7.16–7.02(m,4H),6.98–6.82(m,4H),6.46(d,J＝7.6Hz,2H),6.32(d,J＝6.0Hz,1H),5.02(d,J＝25.8Hz,1H).13C NMR(101MHz,CDCl3)δ161.8,152.1(d,J＝5.5Hz),143.8,136.9(d,J＝8.1Hz),135.4,133.7(d,J＝9.0Hz),133.5(d,J＝6.4Hz),133.1(d,J＝3.9Hz),132.3(d,J＝1.9Hz),131.0(d,J＝8.0Hz),130.3(d,J＝4.9Hz),129.9(d,J＝5.2Hz),129.3,128.3,128.0,128.0(d,J＝130.7Hz),127.9,127.8,127.6,127.2(d,J＝3.3Hz),127.2(d,J＝2.1Hz),126.7,126.2,125.4,122.3,120.8,63.7(d,J＝1.8Hz),51.5(d,J＝80.7Hz).31P NMR(162MHz,CDCl3)δ28.5。
Example fourteen
1l of Rel- (4bS,15S,16S) -11-nitro-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f ] benzo [4,5] [1,2] azophosp-hoxano [1,6-d ] [1,4] oxazepine 15-oxide
According to the method described in example oneUsing 7-nitrodibenzo [ b, f ]][1,4]Taking oxazepine as a raw material to obtain Rel- (4bS,15S,16S) -11-nitro-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f)]Benzo [4,5]][1,2]N-P heterocyclic hexane [1,6-d ]][1,4]Oxazepine 15-oxide, colorless crystals, 25mg, 24%); mp.300-302 deg.C, IR (KBr) v (cm)-1)3060,2925,2854,1736,1590,1517,1491,1341,1259,1243,1211,974,782,745,700.1H NMR(400MHz,CDCl3)δ7.85(d,J＝2.5Hz,1H),7.78(d,J＝9.0Hz,1H),7.54–7.33(m,4H),7.30–6.97(m,12H),6.75(d,J＝6.6Hz,2H),6.61–6.53(m,1H),6.35(d,J＝9.1Hz,1H),5.15(d,J＝29.8Hz,1H).13C NMR(101MHz,CDCl3)δ159.1,152.0(d,J＝4.9Hz),143.1,141.6,140.0(d,J＝2.9Hz),134.0(d,J＝5.0Hz),132.7(d,J＝3.0Hz),132.0,131.7,131.6(d,J＝5.6Hz),130.5(d,J＝4.2Hz),128.5(d,J＝2.3Hz),128.4(d,J＝1.3Hz),128.1(d,J＝3.0Hz),127.8(d,J＝126.3Hz),127.3,126.9(d,J＝6.8Hz),126.8,126.7(d,J＝6.6Hz),125.3(d,J＝2.3Hz),125.1(d,J＝3.7Hz),121.0,120.8,116.8,61.9(d,J＝3.0Hz),51.4(d,J＝78.3Hz).31P NMR(162MHz,CDCl3)δ30.3。
Example fifteen
Rel- (4bS,15S,16S) -7, 11-dichloro-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f ] benzo [4,5] [1,2] azophosp-hoxano [1,6-d ] [1,4] oxazepine 15-oxide 1m
The procedure described in example one was followed using 3, 7-dichlorodibenzo [ b, f ]][1,4]Taking oxazepine as a raw material to obtain Rel- (4bS,15S,16S) -7, 11-dichloro-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f)]Benzo [4,5]][1,2]N-P heterocyclic hexane [1,6-d ]][1,4]Oxazepine 15-oxide, colorless crystals, 108mg, 97%); mp.288-290 deg.C, IR (KBr) v (cm)-1)3059,2924,2852,1597,1492,1261,1243,1210,1116,1049,1017,976,783,750,689.1H NMR(400MHz,CDCl3)δ7.73(d,J＝8.8Hz,1H),7.40(d,J＝2.0Hz,1H),7.31–7.19(m,6H),7.16–7.03(m,8H),6.73(m,4H),6.30(d,J＝7.6Hz,1H),5.09(d,J＝28.4Hz,1H).13C NMR(101MHz,CDCl3)δ159.1,153.1(d,J＝4.9Hz),139.5(d,J＝4.0Hz),135.7,134.1(d,J＝5.3Hz),133.4(d,J＝9.1Hz),132.5,132.3(d,J＝1.7Hz),131.5(d,J＝3.9Hz),131.2(d,J＝5.3Hz),128.77(d,J＝166.0Hz),128.75(d,J＝9.8Hz),128.4,128.2,128.1(d,J＝13.5Hz),127.7(d,J＝2.0Hz),127.1,126.9(d,J＝2.7Hz),126.3(d,J＝6.4Hz),126.1,126.0,125.7,121.7,121.2,61.7(d,J＝1.4Hz),51.4(d,J＝78.7Hz).31P NMR(162MHz,CDCl3)δ28.9。
Example sixteen
Rel- (4bS,15S,16S) -7, 11-dimethyl-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f ] benzo [4,5] [1,2] azophosp-hoxano [1,6-d ] [1,4] oxazepine 15-oxide 1n
The procedure described in example one was followed using 3, 7-dimethyldibenzo [ b, f ]][1,4]Taking oxazepine as a raw material to obtain Rel- (4bS,15S,16S) -7, 11-dimethyl-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f)]Benzo [4,5]][1,2]N-P heterocyclic hexane [1,6-d ]][1,4]Oxazepine 15-oxide, colorless crystal, 63mg, 78%; mp.290-292 deg.C, IR (KBr) v (cm)-1)3060,2923,2854,1502,1258,1211,1127,1088,944,782,730,544.1H NMR(400MHz,CDCl3)δ7.63(d,J＝8.2Hz,1H),7.31–7.00(m,15H),6.84(d,J＝2.0Hz,1H),6.74(d,J＝7.4Hz,2H),6.70–6.66(m,1H),6.27(d,J＝7.8Hz,1H),5.08(d,J＝28.4Hz,1H),2.41(s,3H),2.06(s,3H).13C NMR(101MHz,CDCl3)δ159.4,153.3(d,J＝5.0Hz),141.1,140.8(d,J＝4.1Hz),135.0,134.3(d,J＝5.3Hz),133.6(d,J＝9.1Hz),131.9(d,J＝6.8Hz),131.9,131.7(d,J＝3.2Hz),131.40,131.35(d,J＝5.6Hz),128.8,128.7(d,J＝129.5Hz),128.4,128.1(d,J＝2.3Hz),127.9(d,J＝4.5Hz),127.8,127.5(d,J＝2.9Hz),127.4(d,J＝6.9Hz),126.9(d,J＝1.8Hz),126.2,126.0(d,J＝2.3Hz),125.84,125.81,124.6(d,J＝6.6Hz),121.6,121.2,61.9(d,J＝3.4Hz),51.5(d,J＝78.5Hz),21.2,20.5.31P NMR(162MHz,CDCl3)δ28.3。
Example seventeen
Rel- (4bS,15S,16S) -15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f ] benzo [4,5] [1,2] azophosp-hoxano [1,6-d ] [1,4] thiazepine 15-oxide 1o
Following the procedure described in example one, dibenzo [ b, f ]][1,4]Taking thiazepine as a raw material to obtain Rel- (4bS,15S,16S) -15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f)]Benzo [4,5]][1,2]N-P heterocyclic hexane [1,6-d ]][1,4]Thiazepine 15-oxide, colorless crystal, 75mg, 75%; mp.296-298 deg.C, IR (KBr) v (cm)-1)3060,2971,2927,1736,1618,1471,1438,1324,1220,1066,975,750,701,534.1H NMR(400MHz,CDCl3)δ8.01(d,J＝8.0Hz,1H),7.67–7.62(m,1H),7.32–6.97(m,15H),6.89(td,J＝7.8,1.6Hz,1H),6.81–6.71(m,2H),6.66(td,J＝7.6,1.6Hz,1H),6.42–6.27(m,2H),5.04(d,J＝29.6Hz,1H).13C NMR(101MHz,CDCl3)δ141.9(d,J＝3.7Hz),140.8(d,J＝2.2Hz),140.4,137.0(d,J＝6.8Hz),135.7(d,J＝5.2Hz),135.0(d,J＝4.8Hz),133.5,133.4,133.2,133.0,131.9(d,J＝2.9Hz),131.7(d,J＝5.6Hz),131.6(d,J＝4.4Hz),129.5(d,J＝7.0Hz),129.3,128.9(d,J＝3.1Hz),128.2(d,J＝2.0Hz),127.9,127.7,127.6,127.6,126.5(d,J＝6.7Hz),126.5(d,J＝2.3Hz),126.3(d,J＝1.8Hz),125.1,63.5(d,J＝3.7Hz),51.6(d,J＝77.8Hz).31P NMR(162MHz,CDCl3)δ29.5。
EXAMPLE eighteen
Rel- (4bS,15S,16S) -7-methyl-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f ] benzo [4,5] [1,2] azophosp-cyclohexo [1,6-d ] [1,4] thiazepine 15-oxide 1p
Using 3-methyldibenzo [ b, f ] as described in example one][1,4]Taking thiazepine as a raw material to obtain Rel- (4bS,15S,16S) -7-methyl-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f)]Benzo [4,5]][1,2]N-P heterocyclic hexane [1,6-d ]][1,4]Thiazepine 15-oxide, colorless crystals, 71mg, 69%; mp.306-308 deg.C, IR (KBr) v (cm)-1)3059,2974,1599,1470,1438,1218,1064,975,779,700,530.1H NMR(400MHz,CDCl3)δ8.00(d,J＝8.0Hz,1H),7.47(d,J＝2.0Hz,1H),7.27–6.97(m,14H),6.89(td,J＝8.0,1.6Hz,1H),6.77(dd,J＝6.8,2.0Hz,2H),6.66(td,J＝7.6,1.2Hz,1H),6.41(dd,J＝7.2,1.6Hz,1H),6.30(d,J＝10.0Hz,1H),5.03(d,J＝29.6Hz,1H).13C NMR(101MHz,CDCl3)δ142.0(d,J＝3.7Hz),141.1(d,J＝2.2Hz),140.0,139.7,135.8(d,J＝5.3Hz),135.1(d,J＝4.9Hz),134.3,133.9(d,J＝6.9Hz),133.5(d,J＝9.6Hz),133.1(d,J＝4.1Hz),131.9(d,J＝2.9Hz),131.8(d,J＝5.5Hz),131.7,130.3,129.3,129.0(d,J＝131.5Hz),129.0(d,J＝3.0Hz),128.3(d,J＝2.1Hz),127.9(d,J＝13.2Hz),127.64(d,J＝2.7Hz),127.57,126.6,126.5,126.3(d,J＝1.8Hz),125.0,63.3(d,J＝3.6Hz),51.7(d,J＝77.8Hz),21.1.31P NMR(162MHz,CDCl3)δ29.5。
Example nineteen
Rel- (4bS,15S,16S) -8-fluoro-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f ] benzo [4,5] [1,2] azophospino [1,6-d ] [1,4] thiazepine 15-oxide 1q
Using 4-fluorodibenzo [ b, f ] as described in example one][1,4]Taking thiazepine as a raw material to obtain Rel- (4bS,15S,16S) -8-fluoro-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f)]Benzo [4,5]][1,2]N-P heterocyclic hexane [1,6-d ]][1,4]Thiazepine 15-oxide, colorless crystal, 75mg, 72%; mp.290-292 deg.C, IR (KBr) v (cm)-1)3060,2925,2849,1578,1474,1459,1528,1215,1114,1069,1049,986,950,781,751,702,532.1H NMR(400MHz,CDCl3)δ8.01(d,J＝8.0Hz,1H),7.33–7.00(m,16H),6.77(d,J＝7.6Hz,2H),6.74–6.65(m,1H),6.45(d,J＝6.8Hz,1H),6.38(d,J＝10.0Hz,1H),5.04(d,J＝29.6Hz,1H).13C NMR(101MHz,CDCl3)δ161.8(d,JC-F＝246.3Hz),142.3(d,J＝2.6Hz),140.3,139.7(d,J＝6.6Hz),135.0(d,J＝4.8Hz),134.7(d,J＝5.2Hz),133.6,133.4(d,J＝9.5Hz),132.1(d,J＝2.1Hz),131.7(d,J＝5.7Hz),131.5(d,J＝4.0Hz),130.6(d,J＝8.3Hz),129.8,129.2(d,J＝2.3Hz),128.7(d,JC-P＝132.7Hz),128.6(d,J＝2.5Hz),128.3,128.0,127.9(d,J＝6.5Hz),127.7(d,J＝1.7Hz),126.8(d,J＝6.6Hz),126.4(d,J＝10.3Hz),125.3,116.94(d,J＝23.9Hz),63.1(dd,JC-F,C-P＝2.5,2.5Hz),51.6(d,J＝77.9Hz).19F NMR(376MHz,CDCl3)δ-109.35.31P NMR(162MHz,CDCl3)δ29.8。
Example twenty
Rel- (4bS,15S,16S) -12-chloro-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f ] benzo [4,5] [1,2] azophospino [1,6-d ] [1,4] thiazepine 15-oxide 1r
Using 7-chlorodibenzo [ b, f ] as described in example one][1,4]Taking thiazepine as a raw material to obtain Rel- (4bS,15S,16S) -12-chloro-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f ]]Benzo [4,5]][1,2]N-P heterocyclic hexane [1,6-d ]][1,4]Thiazepine 15-oxide, colorless crystal, 93mg, 89%; mp.286-288 deg.C, IR (KBr) v (cm)-1)3059,2925,2849,1736,1572,1460,1439,1214,1115,1014,985,781,750,697,538,521.1H NMR(400MHz,CDCl3)δ8.17(s,1H),7.45–7.12(m,15H),6.90(d,J＝6.2Hz,2H),6.76(d,J＝7.5Hz,1H),6.45(dd,J＝23.6,8.3Hz,2H),5.15(d,J＝29.8Hz,1H).13C NMR(101MHz,CDCl3)δ143.0(d,J＝2.9Hz),140.5,139.8,136.7(d,J＝6.8Hz),134.8,134.8(d,J＝5.1Hz),134.2(d,J＝5.2Hz),133.5(d,J＝4.5Hz),133.4,133.3,132.1(d,J＝2.7Hz),131.7(d,J＝5.8Hz),131.2,129.8(d,J＝10.1Hz),129.0(d,J＝2.7Hz),128.6(d,J＝131.4Hz),128.3(d,J＝2.1Hz),128.0(d,J＝13.1Hz),127.7,126.6(d,J＝6.8Hz),126.4,125.1,63.6(d,J＝3.5Hz),51.6(d,J＝77.5Hz).31P NMR(162MHz,CDCl3)δ29.8。
Example twenty one
Rel- (4bS,15S,16R) -16- (2-fluorophenyl) -11-methyl-15-phenyl-4 b, 16-dihydrodibenzo [ b, f ] benzo [4,5] [1,2] azophosp-hoxano [1,6-d ] [1,4] oxazepine 15-oxide 1S
Following the procedure described in example one, using azo (2-fluorophenyl) (diphenyl) phosphine oxide and 7-methyldibenzo [ b, f ]][1,4]Taking oxazepine as a raw material to obtain Rel- (4bS,15S,16R) -16- (2-fluorophenyl) -11-methyl-15-phenyl-4 b, 16-dihydrodibenzo [ b, f]Benzo [4,5]][1,2]N-P heterocyclic hexane [1,6-d ]][1,4]Oxazepine 15-oxide, colorless crystal, 90mg, 87%; mp.272-274 ℃.1H NMR(400MHz,CDCl3)δ7.57(d,J＝2.0Hz,1H),7.43–7.18(m,10H),7.12–7.06(m,3H),7.02(t,J＝9.2Hz,1H),6.91(d,J＝8.0Hz,1H),6.79(dd,J＝7.2,1.6Hz,1H),6.68(t,J＝7.6Hz,1H),6.59(dd,J＝8.0,2.0Hz,1H),6.32(d,J＝7.2Hz,1H),6.20(tt,J＝7.6,2.0Hz,1H),5.53(d,J＝27.8Hz,1H),2.01(s,3H).31P NMR(162MHz,CDCl3)δ27.28(d,J＝1.2Hz).13C NMR(101MHz,CDCl3)δ161.6(dd,JC-F,C-P＝247.7,6.3Hz),159.1,151.4(d,J＝5.3Hz),140.1(d,J＝4.6Hz),135.1,134.2(d,J＝2.7Hz),133.4(d,J＝9.2Hz),133.3(d,J＝5.7Hz),132.0(d,J＝2.2Hz),131.4,130.5,129.1(d,J＝8.3Hz),128.6(d,JC-P＝134.0Hz),128.2,128.0,127.8(d,J＝13.5Hz),127.0,126.9,125.9,125.3,123.1,121.1,120.2,120.1(d,J＝3.6Hz),120.0(d,J＝3.3Hz),115.7(d,J＝22.9Hz),62.7(d,J＝3.1Hz),42.5(d,J＝81.1Hz),20.7.31P NMR(162MHz,CDCl3)δ27.3(d,J＝1.6Hz).19F NMR(377MHz,CDCl3)δ-114.2。
Example twenty two
Rel- (4bS,15S,16R) -11-chloro-16- (2-fluorophenyl) -15-phenyl-4 b, 16-dihydrodibenzo [ b, f ] benzo [4,5] [1,2] azophosp-hoxano [1,6-d ] [1,4] oxazepine 15-oxide 1t
Following the procedure described in example one, using azo (2-fluorophenyl) (diphenyl) phosphine oxide and 7-chlorodibenzo [ b, f][1,4]Taking oxazepine as a raw material to obtain Rel- (4bS,15S,16R) -11-chloro-16- (2-fluorophenyl) -15-phenyl-4 b, 16-dihydrodibenzo [ b, f)]Benzo [4,5]][1,2]N-P heterocyclic hexane [1,6-d ]][1,4]Oxazepine 15-oxide, colorless crystal, 70mg, 65%; mp.280-282 deg.C, IR (KBr) v (cm)-1)3061,1736,1585,1488,1237,1214,1113,902,783,749,695,576.1H NMR(400MHz,CDCl3)δ7.67–7.63(m,1H),7.39–6.97(m,15H),6.70–6.58(m,3H),6.27(d,J＝7.4Hz,1H),6.11(t,J＝7.5Hz,1H),5.50(d,J＝28.2Hz,1H).13C NMR(101MHz,CDCl3)δ161.6(dd,JC-F,C-P＝247.8,6.6Hz),158.82,153.77(d,J＝5.1Hz),140.1(d,J＝4.4Hz),133.4(d,J＝8.9Hz),133.2(d,J＝5.4Hz),132.4(d,J＝2.8Hz),131.6,131.5(dd,J＝4.4,2.4Hz),130.9,129.6,129.3(dd,J＝8.5,2.6Hz),128.3,128.2(d,JC-P＝133.4Hz),128.1(d,J＝13.1Hz),127.64,127.56,127.2(d,J＝1.6Hz),127.0(d,J＝3.3Hz),126.4(d,J＝1.9Hz),125.9,125.4,123.2(dd,J＝3.0,3.0Hz),121.2(d,J＝19.6Hz),119.4(dd,J＝13.8,3.8Hz),116.0(d,J＝1.9Hz),115.8(d,J＝1.8Hz),62.4(d,J＝2.9Hz),42.2(d,J＝79.0Hz).31P NMR(162MHz,CDCl3)δ28.0(d,J＝2.9Hz).19F NMR(376MHz,CDCl3)δ-114.2。
Example twenty three
Rel- (4bS,15S,16S) -11-methyl-15-phenyl-16- (4-methylphenyl) -4b, 16-dihydrodibenzo [ b, f ] benzo [4,5] [1,2] azophosp-hoxazolo [1,6-d ] [1,4] oxazepine 15-oxide 1u and Rel- (4bS,15S,16S) -3, 11-dimethyl-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f ] benzo [4,5] [1,2] azophosp-hoxazolo [1,6-d ] [1,4] oxazepine 15-oxide 1 u'
Following the procedure described in example one, using azo (4-methylphenyl) (diphenyl) phosphine oxide and 7-methyldibenzo [ b, f ]][1,4]Taking oxazepine as a raw material to obtain Rel- (4bS,15S,16S) -11-methyl-15-phenyl-16- (4-methylphenyl) -4b, 16-dihydrodibenzo [ b, f)]Benzo [4,5]][1,2]N-P heterocyclic hexane [1,6-d ]][1,4]Oxazepine 15-oxide 1u and Rel- (4bS,15S,16S) -3, 11-dimethyl-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f ] S]Benzo [4,5]][1,2]N-P heterocyclic hexane [1,6-d ]][1,4]Oxazepine 15-oxide 1 u', colorless crystals, 90mg, 85%; mp.292-294 deg.C, IR (KBr) v (cm)-1)3058,3028,2922,2855,1600,1504,1490,1264,1213,1119,989,908,825,731,696,571,523.1H NMR(400MHz,CDCl3)δ7.56(d,J＝2.0Hz,2H),7.40–7.02(m,14H),6.95–6.89(m,2H),6.74–6.61(m,2H),6.60–6.46(m,1H),6.33–6.20(m,2H),5.07(d,J＝28.7Hz,0.36×1H,3u),5.01(d,J＝27.9Hz,0.64×1H,3u’),2.28(s,3H),1.99(s,0.64×3H,3u’),1.97(s,0.36×3H,3u).13C NMR(101MHz,CDCl3)δ159.7,159.2,151.20(d,J＝4.2Hz),151.15(d,J＝5.1Hz),140.5(d,J＝3.9Hz),139.8(d,J＝4.8Hz),137.2(d,J＝2.9Hz),136.6(d,J＝1.9Hz),134.97,134.95,134.6(d,J＝5.1Hz),134.3(d,J＝2.9Hz),134.0(d,J＝3.1Hz),133.4(d,J＝9.1Hz),133.3,131.8(d,J＝2.9Hz),131.7(d,J＝133.3Hz,3u’),131.64(d,J＝134.8Hz,3u),131.58,131.4,131.1(d,J＝5.3Hz),130.7,130.4,129.3,128.9(d,J＝2.3Hz),128.7,128.5(d,J＝4.1Hz),128.0(d,J＝2.0Hz),127.80,127.75,127.7,127.6,127.4(d,J＝6.8Hz),127.3,126.8(d,J＝1.6Hz),126.6(d,J＝3.4Hz),126.4(d,J＝3.5Hz),125.8(d,J＝1.9Hz),125.54,125.48,125.3,125.2,120.90,120.85,120.1(d,J＝2.0Hz),62.5(d,J＝3.3Hz,3u’),62.0(d,J＝3.4Hz,3u),51.2(d,J＝79.2Hz,3u’),51.0(d,J＝78.9Hz,3u),21.3(3u’),21.0(3u),20.6.31P NMR(162MHz,CDCl3)δ28.6(3u’),28.4(3u)。
Example twenty-four
Rel- (4bS,15S,16S) -16- (4-chlorophenyl) -11-methyl-15-phenyl-4 b, 16-dihydrodibenzo [ b, f ] benzo [4,5] [1,2] azophosp-hoxano [1,6-d ] [1,4] oxazepine 15-oxide 1v and Rel- (4bS,15S,16S) -3-chloro-11-methyl-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f ] benzo [4,5] [1,2] azophosp-hoxano [1,6-d ] [1,4] oxazepine 15-oxide 1 v'
Following the procedure described in example one, using azo (4-chlorophenyl) (diphenyl) phosphine oxide and 7-methyldibenzo [ b, f ]][1,4]Taking oxazepine as a raw material to obtain Rel- (4bS,15S,16S) -16- (4-chlorphenyl) -11-methyl-15-phenyl-4 b, 16-dihydrodibenzo [ b, f]Benzo [4,5]][1,2]N-P heterocyclic hexane [1,6-d ]][1,4]Oxazepine 15-oxide 1v and Rel- (4bS,15S,16S) -3-chloro-11-methyl-15, 16-diphenyl-4 b, 16-dihydrodibenzo [ b, f ]]Benzo [4,5]][1,2]N-P heterocyclic hexane [1,6-d ]][1,4]Oxazepine 15-oxide 1 v', colorless crystals, 62mg, 56%; mp.292-294 deg.C, IR (KBr) v (cm)-1)2974,2926,1504,1491,1529,1214,1090,1049,881,734,696.1H NMR(400MHz,CDCl3)δ7.55(d,J＝2.4Hz,1H),7.49–7.07(m,15H),6.95(d,J＝8.0Hz,1H),6.80–6.75(m,1H),6.70–6.63(m,1H),6.63–6.55(m,1H),6.30(dd,J＝8.0,2.8Hz,1H),5.08(d,J＝27.9Hz,0.31×1H,3v’),5.07(d,J＝28.7Hz,0.69×1H,3v),2.02(s,0.31×3H,3v’),2.00(s,0.69×3H,3v).13C NMR(101MHz,CDCl3)δ159.7,159.5,151.3(d,J＝5.1Hz),142.5(d,J＝3.8Hz),135.2,133.7(d,J＝3.2Hz),133.49(d,J＝9.3Hz),133.46(d,J＝9.1Hz),133.14,133.11(d,J＝1.7Hz),132.5(d,J＝5.2Hz),132.2(d,J＝2.8Hz),131.6,131.5,131.4,131.3(d,J＝5.5Hz),131.2,128.8(d,J＝6.9Hz),128.4(d,J＝133.4Hz),128.3(d,J＝1.9Hz),128.2,128.04(d,J＝1.6Hz),128.01(d,J＝13.3Hz),127.9(d,J＝13.7Hz),127.2(d,J＝1.5Hz),127.1(d,J＝6.6Hz),126.6(d,J＝3.6Hz),126.5(d,J＝3.4Hz),126.4(d,J＝2.1Hz),125.8,125.7,125.6,125.4,121.2,121.1,120.30,120.26,62.4(d,J＝2.9Hz,3v’),61.8(d,J＝3.4Hz,3v),51.2(d,J＝78.4Hz,3v),51.0(d,J＝78.7Hz,3v’),20.7.31P NMR(162MHz,CDCl3)δ28.1(3v),27.8(3v’)。
Example twenty-five
Rel- (4bS,15S,16S) -11-methyl-15, 16-bis (4-methylphenyl) -4b, 16-dihydrodibenzo [ b, f ] benzo [4,5] [1,2] azophospino [1,6-d ] [1,4] oxazepine 15-oxide 1w and Rel- (4bS,15S,16S) -3, 11-dimethyl-15- (4-methylphenyl) -16-phenyl-4 b, 16-dihydrodibenzo [ b, f ] benzo [4,5] [1,2] azophospino [1,6-d ] [1,4] oxazepine 15-oxide 1 w'
Following the procedure described in example one, using azo (phenyl) (bis (4-methylphenyl)) phosphine oxide and 7-methyldibenzo [ b, f ]][1,4]Taking oxazepine as a raw material to obtain Rel- (4bS,15S,16S) -11-methyl-15, 16-di (4-methylphenyl) -4b, 16-dihydrodibenzo [ b, f)]Benzo [4,5]][1,2]N-P heterocyclic hexane [1,6-d ]][1,4]Oxazepine 15-oxide 1w and Rel- (4bS,15S,16S) -3, 11-dimethyl-16-phenyl-15- (4-methylphenyl) -4b, 16-dihydrodibenzo [ b, f ]]Benzo [4,5]][1,2]N-P heterocyclic hexane [1,6-d ]][1,4]Oxazepine 15-oxide 1 w', colorless crystals, 40mg, 39%; mp.284-286 deg.C, IR (KBr) v (cm)-1)3030,2922,2859,1601,1505,1491,1264,1215,1112,988,908,811,731,571,521.1H NMR(400MHz,CDCl3)δ7.60(s,1H),7.46–7.34(m,3H),7.26–7.18(m,3H),7.15–7.04(m,4H),6.99–6.89(m,4H),6.76–6.54(m,4H),6.38–6.24(m,1H),5.08(d,J＝28.4Hz,1H×0.64,3w’),5.02(d,J＝27.4Hz,1H×0.36,3w),2.32(s,3H),2.25(s,3H),2.04(s,3H×0.64,3w’),2.02(s,3H×0.36,3w).13C NMR(101MHz,CDCl3)δ159.8,159.2,151.3(d,J＝4.7Hz),142.3(d,J＝2.9Hz),140.6(d,J＝4.0Hz),140.0(d,J＝4.8Hz),137.1(d,J＝3.0Hz),136.6(d,J＝1.8Hz),135.0,134.7(d,J＝5.0Hz),134.5(d,J＝3.1Hz),134.1(d,J＝3.4Hz),133.6,133.5(d,J＝2.3Hz),133.4,132.5(d,J＝4.2Hz),131.6,131.4,131.18(d,J＝11.1Hz),131.18,130.7,130.4,128.9(d,J＝2.1Hz),128.63(d,J＝13.7Hz),128.58(d,J＝13.3Hz),128.0(d,J＝6.1Hz),127.91(d,J＝2.4Hz),127.85,127.34(d,J＝6.7Hz),127.25(d,J＝1.8Hz),127.2(d,J＝2.8Hz),126.7,126.6(d,J＝3.4Hz),125.9(d,J＝13.8Hz),125.8(d,J＝1.6Hz),124.7,124.5,120.90,120.85,120.1,62.5(d,J＝3.0Hz,3w),62.1(d,J＝3.2Hz,3w’),51.3(d,J＝79.4Hz,3w),51.1(d,J＝79.1Hz,3w’),21.5(3w’),21.3(3w),21.02(3w’),20.98(3w),20.6,14.1.31P NMR(162MHz,CDCl3)δ29.0(3w),28.8(3w’)。
Example twenty-six
Rel- (4bS,15S,16S) -15, 16-bis (4-chlorophenyl) -11-methyl-4 b, 16-dihydrodibenzo [ b, f ] benzo [4,5] [1,2] azophospine [1,6-d ] [1,4] oxazepine 15-oxide 1x and Rel- (4bS,15S,16S) -3-chloro-15- (4-chlorophenyl) -11-methyl-16-phenyl-4 b, 16-dihydrodibenzo [ b, f ] benzo [4,5] [1,2] azophospine [1,6-d ] [1,4] oxazepine 15-oxide 1 x'
Following the procedure described in example one, using azo (4-methylphenyl) (bis (4-chlorophenyl)) phosphinoxide and 7-methyldibenzo [ b, f ]][1,4]Taking oxazepine as a raw material to obtain Rel- (4bS,15S,16S) -15, 16-di (4-chlorphenyl) -11-methyl-4 b, 16-dihydrodibenzo [ b, f]Benzo [4,5]][1,2]N-P heterocyclic hexane [1,6-d ]][1,4]Oxazepine 15-oxide 1x and Rel- (4bS,15S,16S) -3-chloro-15- (4-chlorophenyl) -11-methyl-16-phenyl-4 b, 16-dihydrodibenzo [ b, f]Benzo [4,5]][1,2]N-P heterocyclic hexane [1,6-d ]][1,4]Oxazepine 15-oxide 1 x', colorless crystals, 107mg, 94%; mp.284-286 deg.C, IR (KBr) v (cm)-1)2923,1507,1491,1214,1120,1086,821,699,571,540.1H NMR(400MHz,CDCl3)δ7.55(s,1H),7.48–7.09(m,13H),7.00–6.94(m,1H),6.81–6.74(m,1H),6.73–6.60(m,3H),6.33–6.23(m,1H),5.09(d,J＝28.0Hz,0.60×1H,3x),5.07(d,J＝28.7Hz,0.40×1H,3x’),2.05(s,0.60×3H,3x),2.03(s,0.40×3H,3x’).13C NMR(101MHz,CDCl3)δ159.4(3x’),159.2(3x),151.4(d,J＝5.1Hz),142.2(d,J＝4.1Hz),139.9(d,J＝4.9Hz),138.8(d,J＝3.9Hz),138.8(d,J＝4.0Hz),135.3,134.8(d,J＝10.0Hz),134.8(d,J＝10.1Hz),133.8(d,J＝2.9Hz),133.6(d,J＝3.6Hz),133.5(d,J＝3.0Hz),133.4(d,J＝5.5Hz),133.2(d,J＝2.4Hz),132.6(d,J＝5.3Hz),132.3(d,J＝5.4Hz),131.5,131.4,131.3(d,J＝4.6Hz),131.16,131.15(d,J＝5.2Hz),130.7,130.6(d,J＝4.6Hz),128.44,128.42,128.37(d,J＝131.8Hz,3x),128.36,128.30,128.29(d,J＝133.1Hz,3x’),128.28,128.1,127.9(d,J＝2.9Hz),127.8,127.62,127.55,127.2(d,J＝1.5Hz),126.9(d,J＝6.6Hz),126.8(d,J＝1.7Hz),126.6(d,J＝3.7Hz),126.5(d,J＝3.4Hz),126.4(d,J＝8.1Hz),126.2,126.0,125.7,125.4,121.2,121.1,120.38,120.36,62.5(d,J＝3.3Hz,3x),61.9(d,J＝3.5Hz,3x’),50.9(d,J＝79.2Hz,3x’),50.8(d,J＝79.6Hz,3x),20.7.31P NMR(162MHz,CDCl3)δ27.2(3x’),26.8(3x)。
Example twenty-seven
Rel- (4bS,15S,16S) -11-chloro-15, 16-bis (4-chlorophenyl) -4b, 16-dihydrodibenzo [ b, f ] benzo [4,5] [1,2] azophospino [1,6-d ] [1,4] oxazepine 15-oxide 1y and Rel- (4bS,15S,16S) -3, 11-dichloro-15- (4-chlorophenyl) -16-phenyl-4 b, 16-dihydrodibenzo [ b, f ] benzo [4,5] [1,2] azophospino [1,6-d ] [1,4] oxazepine 15-oxide 1 y'
Following the procedure described in example one, with azo (phenyl) (bis (4-chlorophenyl)) phosphine oxide and 7-chlorodibenzo [ b, f ]][1,4]Rel- (4bS,15S,16S) -11-chloro-15, 16-di (4-chlorphenyl) -4b, 16-dihydrodibenzo [ b, f ] is obtained by using oxazepine as a raw material]Benzo [4,5]][1,2]N-P heterocyclic hexane [1,6-d ]][1,4]Oxazepine 15-oxide 1y and Rel- (4bS,15S,16S) -3, 11-dichloro-15- (4-chlorophenyl) -16-phenyl-4 b, 16-dihydrodibenzo [ b, f ]]Benzo [4,5]][1,2]N-P heterocyclic hexane [1,6-d ]][1,4]Oxazepine 15-oxide 1 y', colorless crystals, 92mg, 78%; mp.282-284 deg.C, IR (KBr) v (cm)-1)3063,2928,2852,1736,1582,1482,1238,1210,1085,1013,978,902,823,783,742,577,549.1H NMR(400MHz,CDCl3)δ7.76–7.68(m,1H),7.54–7.39(m,2H),7.37–7.24(m,4H),7.22–7.05(m,8H),6.83–6.57(m,4H),6.33(dd,J＝7.2,5.2Hz,1H),5.16(d,J＝28.5Hz,0.50×1H),5.13(d,J＝29.0Hz,0.50×1H).13C NMR(101MHz,CDCl3)δ159.0,158.9,153.8(d,J＝3.0Hz),153.7(d,J＝2.9Hz),142.2(d,J＝3.7Hz),140.0(d,J＝4.1Hz),139.21(d,J＝3.3Hz),139.16(d,J＝3.3Hz),134.8(d,J＝9.8Hz),133.9(d,J＝3.4Hz),133.35,133.33(d,J＝7.7Hz),133.0(d,J＝3.2Hz),132.8(d,J＝3.2Hz),132.6(d,J＝5.1Hz),132.4(d,J＝5.5Hz),131.7(d,J＝5.5Hz),131.5,131.2(d,J＝5.5Hz),131.1,130.7(d,J＝4.5Hz),130.0(d,J＝4.5Hz),129.8(d,J＝8.7Hz),128.7,128.6,128.5(d,J＝1.9Hz),128.4,128.2,128.1(d,J＝133.3Hz),128.0(d,J＝2.7Hz),127.4(d,J＝1.6Hz),127.2(d,J＝6.9Hz),126.8(d,J＝3.1Hz),126.7(d,J＝3.2Hz),126.6(d,J＝6.6Hz),126.4,126.3(d,J＝1.8Hz),126.2(d,J＝2.4Hz),126.0,125.6(d,J＝2.5Hz),121.4,121.3,121.1,62.1(d,J＝3.3Hz),61.6(d,J＝3.3Hz),50.8(d,J＝79.1Hz),50.6(d,J＝79.3Hz).31P NMR(162MHz,CDCl3)δ27.8,27.5。
Claims (6)
1. A pentacyclic benzo-delta-phosphine lactam compound shown as a formula 1;
wherein: x may be an oxygen or sulfur atom; r1、R2、R3And R4Represents an alkyl group or an alkoxy group having 1 to 5 carbon atoms, an aryl group or an aryloxy group having 6 to 8 carbon atoms, fluorine, chlorine, bromine, a cyano group, a nitro group; r1、R2、R3And R4May be the same or different; r3/4And R4/3When R is represented3/4Is R3When R is4/3Is R4And R is3/4Is R4When R is4/3Is R3。
2. A preparation method of pentacyclobenzo-delta-phosphine lactam compound shown in formula 1 is characterized in that diazo (aryl) methyl (diaryl) phosphine oxide compound shown in formula 2 and dibenzo [ b, f ] [1,4] oxygen or sulfur nitrogen hetero-compound shown in formula 3 react to obtain the pentacyclobenzo-delta-phosphine lactam compound shown in formula 1
3. The process for producing pentacyclic benzo- δ -phosphine lactams according to claim 2, wherein the solvent used is dimethylsulfoxide, cyclobutane sulfoxide, dimethylsulfone, sulfolane, acetonitrile, propionitrile, butyronitrile, valeronitrile, chloroform, 1, 2-dichloroethane, tetrachloroethylene, tetrahydrofuran, 1, 4-dioxane, ethylene glycol dimethyl ether, benzene, toluene, xylene, trimethylbenzene, ethylbenzene, toluene, chlorobenzene, dichlorobenzene, trichlorobenzene or a mixture thereof.
4. The process for preparing pentacyclic benzo- δ -phosphine lactams according to claim 2 or 3, wherein the reaction temperature is 50-150 ℃, and the reaction can be carried out by conventional steam heating, electric heating or microwave heating.
5. The process for producing pentacyclic benzo- δ -phosphinolactam compounds according to claim 2 or 3, wherein the reaction temperature is-40 to 150 ℃ and the reaction can be carried out by irradiation with light.
6. The process for producing pentacyclic benzo- δ -phosphine lactam compound according to claim 2 or 3, wherein the reaction conditions are carried out in an anhydrous solvent under nitrogen protection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010836230.7A CN111995643B (en) | 2020-08-19 | 2020-08-19 | Pentacyclic benzo-delta-phosphine lactam compound and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010836230.7A CN111995643B (en) | 2020-08-19 | 2020-08-19 | Pentacyclic benzo-delta-phosphine lactam compound and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111995643A CN111995643A (en) | 2020-11-27 |
| CN111995643B true CN111995643B (en) | 2022-05-17 |
Family
ID=73472975
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010836230.7A Active CN111995643B (en) | 2020-08-19 | 2020-08-19 | Pentacyclic benzo-delta-phosphine lactam compound and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111995643B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113717228A (en) * | 2021-10-18 | 2021-11-30 | 北京化工大学 | Beta-phosphinic lactam compound and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9073956B1 (en) * | 2014-05-02 | 2015-07-07 | Knu-Industry Cooperation Foundation | Dihydro-1H-phosphole 1-oxide derivatives and preparation method thereof |
| CN106946843A (en) * | 2017-03-03 | 2017-07-14 | 北京化工大学 | A kind of preparation method of the oxathiene of 3 acyl group 1,4 |
| CN107739365A (en) * | 2017-11-13 | 2018-02-27 | 北京化工大学 | A kind of preparation method of the base methanol of benzo [b] [1,4] oxygen thia hexamethylene 3 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101448582B1 (en) * | 2014-05-02 | 2014-10-13 | 강원대학교산학협력단 | Novel cyclic phosphinate derivatives and its preparation method |
| KR101452337B1 (en) * | 2014-05-30 | 2014-10-22 | 강원대학교산학협력단 | Novel phosphinine oxide derivatives and its preparation method |
-
2020
- 2020-08-19 CN CN202010836230.7A patent/CN111995643B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9073956B1 (en) * | 2014-05-02 | 2015-07-07 | Knu-Industry Cooperation Foundation | Dihydro-1H-phosphole 1-oxide derivatives and preparation method thereof |
| CN106946843A (en) * | 2017-03-03 | 2017-07-14 | 北京化工大学 | A kind of preparation method of the oxathiene of 3 acyl group 1,4 |
| CN107739365A (en) * | 2017-11-13 | 2018-02-27 | 北京化工大学 | A kind of preparation method of the base methanol of benzo [b] [1,4] oxygen thia hexamethylene 3 |
Non-Patent Citations (2)
| Title |
|---|
| Palladium-Catalyzed Enantioselective C-H Arylation for the Synthesis of P-Stereogenic Compounds;Lin, Zi-Qi 等;《Angewandte Chemie, International Edition》;20150402;第54卷(第21期);第6265-6269页 * |
| 电子受体烯酮参与Staudinger反应立体选择性的实验与理论研究;亓恒振 等;《中国化学会全国第三届有机合成化学与过程学术讨论会论文摘要集》;20101231;第79-80页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111995643A (en) | 2020-11-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111995643B (en) | Pentacyclic benzo-delta-phosphine lactam compound and preparation method thereof | |
| AU2020201527B2 (en) | Phosphoramidate compound and preparation method and crystal thereof | |
| WO2014012495A1 (en) | Chiral α-methylene-β-lactam compound and preparation method and application thereof | |
| CN112661764A (en) | Tetrahydrofuran indole compound and preparation method and application thereof | |
| Caine et al. | Synthesis of (.+-.)-umbelactone | |
| Osuna et al. | Asymmetric synthesis of amathamides A and B: novel alkaloids isolated from Amathia wilsoni | |
| CN109651385A (en) | A kind of preparation method of pyrans [3,2-a] carbazole compound | |
| CN115197058B (en) | Anticancer natural product Dysideanone B analogue and preparation method thereof | |
| CN110724080B (en) | Synthetic method of aryl selenium cyanogen compound | |
| CN114591331A (en) | Triazole derivative and application thereof in anti-cancer drugs | |
| CN111518010B (en) | Synthesis of bicyclo [3,3,0] cyclooctanone derivatives and preparation method thereof | |
| Gelpke et al. | Resolution and some properties of (1, 1′)-bi (dibenzofuranyl)-2, 2′-diol (BIFOL) | |
| CN110028487B (en) | Preparation method of thiochromanone compound | |
| Gataullin | Halolactonization of N-Acyl-N-(2-cyclohex-1-en-1-yl-6-methylphenyl) glycines: Towards Production of 4, 1-Benzoxazoheterocycles | |
| Kudashev et al. | Methylene C (sp3)− H Arylation Enables the Stereoselective Synthesis and Structure Revision of Indidene Natural Products | |
| CN113461700B (en) | Application of oxygen-promoted dearomatization reaction in construction of spiro-dienone skeleton | |
| CN115260136B (en) | Phthalide compound and preparation method thereof | |
| CN113651755B (en) | 4-azafluorene compound and preparation method and application thereof | |
| CN110003235B (en) | Isoxazole succinimide compound and synthetic method thereof | |
| CN112142709B (en) | Synthetic method of 6-aryl-2,3,4,5-tetrahydrooxaheptin-3-alcohol derivative | |
| CN108948034A (en) | A kind of chroman bridged ring isoindolone and preparation method thereof | |
| CN113717228A (en) | Beta-phosphinic lactam compound and preparation method thereof | |
| CN112094234B (en) | Synthesis method of 6-phenyl-2, 3,4, 7-tetrahydro-1H-3-azepine derivative | |
| TOMIOKA et al. | Stereoselective Reactions. XII.: Synthesis of Antitumor-Active Steganacin Analogs, Picrosteganol and Epipicrosteganol, by Selective Isomerization | |
| CN116655641A (en) | Tryptamine ketimine compound and derivative thereof, and synthetic method and application thereof |
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 |