CN106588984B - A kind of preparation method of 6- phosphoryls substitution phenanthridines analog derivative - Google Patents
A kind of preparation method of 6- phosphoryls substitution phenanthridines analog derivative Download PDFInfo
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- 150000005053 phenanthridines Chemical class 0.000 title claims abstract description 13
- 238000006467 substitution reaction Methods 0.000 title claims description 5
- 238000002360 preparation method Methods 0.000 title description 8
- -1 diaryl oxygen phosphorus Chemical compound 0.000 claims abstract description 18
- 238000006243 chemical reaction Methods 0.000 claims abstract description 13
- 150000002540 isothiocyanates Chemical class 0.000 claims abstract description 7
- 238000010189 synthetic method Methods 0.000 claims abstract description 7
- 239000002904 solvent Substances 0.000 claims abstract description 5
- 125000001424 substituent group Chemical group 0.000 claims abstract description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 239000003054 catalyst Substances 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- UOGMEBQRZBEZQT-UHFFFAOYSA-L manganese(2+);diacetate Chemical compound [Mn+2].CC([O-])=O.CC([O-])=O UOGMEBQRZBEZQT-UHFFFAOYSA-L 0.000 claims description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims 1
- 229960001760 dimethyl sulfoxide Drugs 0.000 claims 1
- 229940071125 manganese acetate Drugs 0.000 claims 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 claims 1
- 230000035484 reaction time Effects 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 abstract description 12
- 238000000034 method Methods 0.000 abstract description 7
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- 239000012043 crude product Substances 0.000 abstract description 4
- 239000000047 product Substances 0.000 abstract description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 239000000706 filtrate Substances 0.000 abstract description 3
- 239000012074 organic phase Substances 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- 238000000926 separation method Methods 0.000 abstract description 3
- 238000004440 column chromatography Methods 0.000 abstract description 2
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 abstract 1
- 238000006555 catalytic reaction Methods 0.000 abstract 1
- 229910052748 manganese Inorganic materials 0.000 abstract 1
- 239000011572 manganese Substances 0.000 abstract 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 10
- 238000001228 spectrum Methods 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 3
- 230000036571 hydration Effects 0.000 description 3
- 238000006703 hydration reaction Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000007800 oxidant agent Substances 0.000 description 3
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 150000002527 isonitriles Chemical class 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- RDOWQLZANAYVLL-UHFFFAOYSA-N phenanthridine Chemical group C1=CC=C2C3=CC=CC=C3C=NC2=C1 RDOWQLZANAYVLL-UHFFFAOYSA-N 0.000 description 2
- FANCTJAFZSYTIS-IQUVVAJASA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-7a-methyl-1-[(2r)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C([C@@H](C)[C@@H]1[C@]2(CCCC(/[C@@H]2CC1)=C\C=C\1C([C@@H](O)C[C@H](O)C/1)=C)C)CS(=N)(=O)C1=CC=CC=C1 FANCTJAFZSYTIS-IQUVVAJASA-N 0.000 description 1
- QMGHHBHPDDAGGO-IIWOMYBWSA-N (2S,4R)-1-[(2S)-2-[[2-[3-[4-[3-[4-[[5-bromo-4-[3-[cyclobutanecarbonyl(methyl)amino]propylamino]pyrimidin-2-yl]amino]phenoxy]propoxy]butoxy]propoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide Chemical compound CN(CCCNC1=NC(NC2=CC=C(OCCCOCCCCOCCCOCC(=O)N[C@H](C(=O)N3C[C@H](O)C[C@H]3C(=O)NCC3=CC=C(C=C3)C3=C(C)N=CS3)C(C)(C)C)C=C2)=NC=C1Br)C(=O)C1CCC1 QMGHHBHPDDAGGO-IIWOMYBWSA-N 0.000 description 1
- HDACWFZGZYNUEP-UHFFFAOYSA-N Fc(cc1)ccc1-c1ccccc1N=C=S Chemical compound Fc(cc1)ccc1-c1ccccc1N=C=S HDACWFZGZYNUEP-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 239000003972 antineoplastic antibiotic Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000006269 biphenyl-2-yl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C(*)C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 125000004437 phosphorous atom Chemical group 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 238000007348 radical reaction Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000002699 waste material Substances 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
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/5765—Six-membered rings condensed with carbocyclic rings or carbocyclic ring systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
Abstract
The invention discloses a kind of method for preparing 6 phosphoryls and replacing phenanthridines analog derivative, this method belongs to technical field of organic synthesis, and the method is：Xenyl isothiocyanates and diaryl oxygen phosphorus are added into reactor, under manganese catalysis, it is heated in solvent, it is cooled to room temperature after completion of the reaction, system is washed after being diluted with ethyl acetate with saturated sodium-chloride, merge organic phase, then obtains crude product with Rotary Evaporators concentration filtrate, last column chromatography for separation obtains product.The synthetic method is easy to operate, and raw material is easily prepared, and can introduce multiple substituent groups simultaneously, and product is easy to purifies and separates, and yield is high, is suitable for 6 phosphoryls of synthesis and replaces phenanthridines analog derivative.Its reaction equation is as follows：
Description
Technical field
The invention belongs to technical field of organic synthesis, more particularly to a kind of preparation side of 6- phosphoryls phenanthridines analog derivative
Method.
Background technology
Phosphorous organic molecule is widely used in Synthetic Organic Chemistry, pharmaceutical chemistry as a kind of important organic compound
And in the multiple fields such as materials chemistry.Meanwhile the ligand that organophosphor is important as one kind, in the Synthetic Organic Chemistry of metal catalytic
With vital effect is also played in Coordinative Chemistry.
Phenanthridines is not only the nuclear structure unit of many natural products and the basic framework of many important drugs molecules.
Many includes that the molecule of phenanthridines skeleton all shows the bioactivity of anticancer antibiotic.Phosphorus atoms are introduced into phenanthridines skeleton
It has potential application.
In recent years, the synthetic method of 6- phosphoryls phenanthridines class compound attracts wide attention, the preparation of such compound
Method passes through mainly using xenyl isonitrile and diaryl oxygen phosphorus as raw material under the conditions of inorganic oxidizer or photochemical catalyst
Radical reaction synthesizes (Org.Lett.2014,16,250-253；Tetrahedron.2014,70,6985–6990；
Org.Lett.,2016,18,4928–4931).However, these preparation methods have the shortcomings that it is apparent：1) raw material xenyl isonitrile
It is difficult to prepare；2) these methods all use excessive oxidant, and post-processing is complicated, and production cost is high；3) it is at least needed for reaction
2.5 times of equivalent diaryl oxygen phosphorus waste big content of starting materials, and severe reaction conditions do not meet Atom economy, lack practical value.
Invention content
The present invention provides a kind of preparation method of 6- phosphoryls phenanthridines analog derivative.We utilize 2- biphenyl in the present invention
The reaction of base isothiocyanates and diaryl oxygen phosphorus is prepared for a series of 6- phosphoryls phenanthridines analog derivatives, provides a kind of valence
Lattice are cheap, synthesize to environmental-friendly synthetic method, more simple and effective 6- phosphoryl phenanthridines analog derivatives, the 6- phosphoryls
Phenanthridines analog derivative has structure shown in formula I：
In Formulas I, R1For hydrogen atom, methyl, methoxyl group, fluorine atom, phenyl；R2For hydrogen atom, methyl, chlorine atom；Ar is benzene
Base, substituted-phenyl, substituent group are methyl, methoxyl group, fluorine atom.
Synthesis 6- phosphoryl phenanthridines analog derivatives according to the present invention, reaction equation such as Formula II：
The preparation method detailed process of the 6- phosphoryl phenanthridine derivatives of the present invention is as follows：
It is former with 2- xenyls isothiocyanates and diaryl oxygen phosphorus in certain reaction temperature, solvent and catalyst
Material synthesis 6- phosphoryl phenanthridines analog derivatives.
The dosage of xenyl isothiocyanates is 1.5 times of diaryl oxygen phosphorus dosage, and reaction temperature is 110 DEG C, and solvent is
N,N-Dimethylformamide, catalyst are four hydration manganese acetates.
Specific implementation step is the addition diaryl oxygen phosphorus into reactor, 2- xenyl isothiocyanates, four hydration acetic acid
System is put into 110 DEG C of oil baths and stirs by manganese, n,N-Dimethylformamide.After reaction, after system being cooled down, second is added
Acetoacetic ester diluted system is washed in six times with saturated nacl aqueous solution, merges organic phase, and magnesium sulfate drying is added, filters,
Rotary Evaporators concentration filtrate obtains crude product, with eluant, eluent (petroleum ether：Ethyl acetate=2:1) column chromatography for separation obtains product.
Beneficial effects of the present invention are：The synthetic method science of 6- phosphoryls phenanthridines analog derivative provided by the invention is closed
Reason is avoided using excessive oxidant and diaryl oxygen phosphorus, reduces production cost, but also simple with synthetic method,
The features such as yield is high, product is easy to purifying.
Description of the drawings
Fig. 1 is compound 3a's prepared by embodiment 11H NMR and13C NMR spectras；
Fig. 2 is compound 3e's prepared by embodiment 51H NMR and13C NMR spectras；
Fig. 3 is compound 3i's prepared by embodiment 91H NMR and13C NMR spectras.
Specific implementation mode
The present invention will be further described in detail with specific embodiment below in conjunction with the accompanying drawings；
Experimental method described in following embodiments is unless otherwise specified conventional method；The reagent and material, such as
Without specified otherwise, commercially obtain.
Embodiment 1
The preparation of 6- phosphoryl phenanthridines 3a
Into the heavy wall pressure pipe of 10ml, xenyl isothiocyanates 1a (0.4mmol, 84.4mg), diaryl oxygen is added
Phosphorus 2a (0.6mmol, 121.2mg), four hydration manganese acetates (0.4mmol, 98.1mg), is added n,N-Dimethylformamide (2ml),
After charging, 6.0h is reacted at 110 DEG C.After reaction system cooling, 10ml ethyl acetate diluting reaction systems are added, are used in combination
30ml saturated nacl aqueous solutions are washed in six times, merge organic phase, and magnesium sulfate is added and dries 30 minutes, filtering, filtrate rotation
Turn to be concentrated by evaporation and obtains crude product.Crude product eluant, eluent (petroleum ether：Ethyl acetate=2:1) post separation (200-300 mesh silicon
Glue), white solid product is obtained through NMR, it was demonstrated that is 6- phosphoryl phenanthridines 3a, yield 68%.
Spectrum elucidation data 3a：
1H NMR(CDCl3,500MHz):δ7.43-7.47(m,4H),7.50-7.54(m,2H),7.68-7.76 (m,
3H), 7.86 (t, J=7.6Hz, 1H), 7.92-7.96 (m, 4H), 8.06 (t, J=4.6Hz, 1H), 8.61 (t, J=4.6Hz,
1H), 8.67 (d, J=8.2Hz, 1H), 9.51 (d, J=7.9Hz, 1H)13C NMR(CDCl3,125MHz):δ122.2,
(124.4,128.0,128.2 d, J=10.9Hz), 128.6,128.7,128.8,131.2 (d, J=14.2Hz), 131.7,
132.4 (d, J=6.5Hz), 133.4,142.8 (d, J=21.9Hz), 156.9 (d, J=128.3Hz)
Embodiment 2
The 1a in example 1 is replaced with 1b, for other experiment conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation data 3b：
1H NMR(CDCl3,500MHz):δ 2.56 (s, 3H), 7.42-7.45 (m, 4H), 7.51 (t, J=7.3Hz, 2H),
7.65-7.72 (m, 3H), 7.94 (q, J=6.3Hz, 4H), 8.03 (d, J=7.9Hz, 1H), 8.54 (d, J=3.7Hz, 2H),
9.33(s,1H).13C NMR(CDCl3,125MHz):δ 21.9,121.9,124.4,127.7,128.1 (d, J=12.0Hz),
(128.7,130.5,131.0,131.6,132.3 d, J=8.0Hz), 132.8 (d, J=16.4Hz), 133.6,138.1,
142.4 (d, J=23.9Hz), 156.3 (d, J=128.7Hz)
Embodiment 3
The 1a in example 1 is replaced with 1c, for other experiment conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation data 3c：
1H NMR(CDCl3,500MHz):δ 3.94 (s, 3H), 7.43-7.48 (m, 5H), 7.64 (t, J=7.4Hz, 2H),
7.69 (t, J=7.6Hz, 2H), 7.97 (q, J=6.3Hz, 4H), 8.04 (d, J=8.1Hz, 1H), 8.50 (d, J=7.9Hz,
1H), 8.54 (d, J=9.1Hz, 1H), 9.03 (d, J=2.2Hz, 1H)13C NMR(CDCl3,125MHz):δ55.6,107.5,
(121.6,122.6,123.6,124.5,127.1,127.6,128.1 d, J=11.4Hz), 128.8,129.4 (d, J=
22.9Hz), 131.1,131.6,132.3 (d, J=7.9Hz), 132.6,133.5,142.1 (d, J=22.8Hz), 155.5 (d,
), J=129.6Hz 158.8.
Embodiment 4
The 1a in example 1 is replaced with 1d, for other experiment conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation data 3d：
1H NMR(CDCl3,500MHz):δ 7.46-7.54 (m, 6H), 7.60 (t, J=7.0Hz, 1H), 7.73 (q, J=
6.8Hz, 2H), 7.96 (q, J=6.3Hz, 4H), 8.08 (d, J=7.6Hz, 1H), 8.54 (d, J=7.3Hz, 1H), 8.64 (d,
J=5.1Hz, 1H), 9.33 (dd, J=1.9,9.8Hz, 1H)13C NMR(CDCl3,125MHz):δ 113.2 (d, J=
23.3Hz), 120.5 (d, J=23.9Hz), 121.9,124.0,124.5 (d, J=8.0Hz), 128.2 (d, J=12.2Hz),
128.6,129.0 (d, J=9.2Hz), 129.2,129.3 (d, J=6.4Hz), 131.2,131.8,132.3 (d, J=
9.0Hz), 133.2,142.4 (d, J=21.9Hz), 156.0 (dd, J=3.8,128.3Hz), 161.3 (d, J=249.3Hz)
Embodiment 5
The 1a in example 1 is replaced with 1e, for other experiment conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation data 3e：
1H NMR(CDCl3,500MHz):δ 7.38 (t, J=7.3Hz, 1H), 7.44-7.48 (m, 6H), 7.52 (t, J=
7.2Hz, 2H), 7.71 (t, J=9.5Hz, 4H), 7.98-8.02 (m, 4H), 8.07-8.11 (m, 2H), 8.58 (d, J=
6.4Hz, 1H), 8.68 (d, J=8.7Hz, 1H), 9.84 (s, 1H)13C NMR(CDCl3,125MHz):δ122.1,122.7,
124.2,126.4,127.5,127.8,128.2 (d, J=12.1Hz), 128.4,128.6,128.9,129.0,130.0,
131.1,131.6,132.2 (d, J=9.0Hz), 133.5,140.1 (d, J=55.2Hz), 142.7 (d, J=22.9Hz),
157.0 (d, J=128.7Hz)
Embodiment 6
The 1a in example 1 is replaced with 1f, for other experiment conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation data 3f：
1H NMR(CDCl3,500MHz):δ2.63(s,3H),7.72-7.45(m,4H),7.49-7.54(m,3H),7.67
(t, J=7.6Hz, 1H), 7.82 (t, J=7.6Hz, 1H), 7.93 (q, J=6.6Hz, 5H), 8.37 (s, 1H), 8.63 (d, J=
7.93Hz, 1H), 9.48 (d, J=8.3Hz, 1H)13C NMR(CDCl3,125MHz):δ22.1,121.6,122.0,124.2,
(127.7,128.1 d, J=11.0Hz), 128.5,130.4,130.8 (d, J=18.9Hz), 131.6,132.3 (d, J=
7.1Hz), 132.8,133.6,139.0,141.2 (d, J=23.4Hz), 155.6 (d, J=129.4Hz)
Embodiment 7
The 1a in example 1 is replaced with 1g, for other experiment conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation data 3g：
1H NMR(CDCl3,500MHz):δ 7.43-7.46 (m, 4H), 7.52 (t, J=7.2Hz, 2H), 7.64 (dd, J=
8.9,2.2Hz, 1H), 7.72 (t, J=7.6Hz, 1H), 7.85-7.93 (m, 5H), 7.98 (d, J=8.7Hz, 1H), 8.55 (d,
J=2.1Hz, 1H), 8.6 (s, 1H), 9.50 (d, J=9.5Hz, 1H)13C NMR(CDCl3,125MHz):δ121.8,122.1,
125.5,128.2 (d, J=11.0Hz), 128.7 (d, J=26.3Hz), 129.3,131.3,131.8,132.3 (d, J=
7.4Hz), 132.6,133.2,134.9,141.1 (d, J=22.9Hz), 157.4 (d, J=127.7Hz)
Embodiment 8
The 2a in example 1 is replaced with 2b, for other experiment conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation data 3h：
1H NMR(CDCl3,500MHz):δ 2.38 (s, 6H), 7.24 (s, 4H), 7.66-7.71 (m, 3H), 7.81 (t, J=
9.6Hz, 5H), 8.06 (t, J=4.6Hz, 1H), 8.59 (d, J=7.7Hz, 1H), 8.64 (d, J=7.7Hz, 1H), 9.52 (d,
J=7.9Hz, 1H)13C NMR(CDCl3,125MHz):δ 21.6,122.0,124.3,127.8,128.6,128.7 (d, J=
5.4Hz), 128.9 (d, J=11.8Hz), 129.4,130.3,130.9,131.2,132.3 (d, J=8.0Hz), 132.5,
142.0,142.8 (d, J=22.9Hz), 157.4 (d, J=125.7Hz)
Embodiment 9
The 2a in example 1 is replaced with 2c, for other experiment conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation data 3i：
1H NMR(CDCl3,500MHz):δ 3.82 (s, 6H), 6.95 (q, J=3.5Hz, 4H), 7.67-7.73 (m, 3H),
7.84 (q, J=6.64Hz, 5H), 8.07 (t, J=4.6Hz, 1H), 8.59 (t, J=4.58Hz, 1H), 8.65 (d, J=
8.06Hz, 1H), 9.53 (d, J=8.54Hz, 1H)13C NMR(CDCl3,125MHz):δ 55.2,113.7 (d, J=
12.0Hz), 122.0,124.1 (d, J=34.9Hz), 124.9,127.8,128.6 (d, J=13.9Hz), 131.0 (d, J=
28.2Hz), 132.5,134.1 (d, J=8.0Hz), 142.7 (d, J=22.9Hz), 157.6 (d, J=127.7Hz),
162.2.HRMS(ESI-TOF,[M+H]+):calcd for C27H23NO3P,440.1410,found 440.1410.
Embodiment 10：
The 2a in example 1 is replaced with 2d, for other experiment conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation data 3j：
1H NMR(CDCl3,500MHz):δ 7.13-7.17 (m, 4H), 7.70-7.77 (m, 3H), 7.88 (t, J=7.6Hz,
1H), 7.90-7.96 (m, 4H), 8.06 (t, J=4.8Hz, 1H), 8.62 (t, J=4.6Hz, 1H), 8.68 (d, J=8.2Hz,
1H), 9.48 (d, J=8.5Hz, 1H)13C NMR(CDCl3,125MHz):δ 115.6 (dd, J=13.6,20.7Hz),
122.2,124.4,127.7 (d, J=23.9Hz), 128.2 (d, J=43.9Hz), 128.2,128.9 (d, J=21.6Hz),
131.1 (d, J=25.9Hz), 132.6 (d, J=5.6Hz), 134.7 (t, J=8.8Hz), 142.6 (d, J=23.9Hz),
156.3 (d, J=130.6Hz), 165.1 (d, J=252.3Hz) .HRMS (ESI-TOF, [M+H]+):calcd for
C25H17F2NOP,416.1010,found 416.1010.
Table 1
Claims (2)
1. a kind of synthetic method of 6- phosphoryls substitution phenanthridines analog derivative, the 6- phosphoryls substitution phenanthridines analog derivative have
Structure shown in formula I：
In Formulas I, R1For hydrogen atom, methyl, methoxyl group, fluorine atom, phenyl；R2For hydrogen atom, methyl, chlorine atom；Ar be phenyl,
Substituted-phenyl, substituent group are methyl, methoxyl group, chlorine atom；
It is characterized in that it is 1 that molar ratio is added into heavy wall pressure pipe：1.5 xenyl isothiocyanates and diaryl oxygen phosphorus, add
Enter the catalyst four that molar ratio is 1.0 and be hydrated manganese acetate, n,N-Dimethylformamide, methyl sulfoxide, nitromethane, toluene is added
The solvent of one of them, system is put into oil bath and is stirred to react；Its reaction equation is as follows：
2. the synthetic method of a kind of 6- phosphoryls substitution phenanthridines analog derivative described in accordance with the claim 1, it is characterized in that solvent
For n,N-Dimethylformamide, reaction temperature is 110 DEG C, reaction time 6h.
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| "Silver-catalyzed 2-isocyanobiaryls insertion/cyclization with phosphine oxides: synthesis of 6-phosphorylated phenanthridines";Cao J J. et al;《Tetrahedron 》;20140724;第70卷;第6985-6990页 * |
| "Synthesis of phenanthridin-6-yldiphenylphosphine oxides by oxidative cyclization of 2-isocyanobiphenyls with diarylphosphine oxides";Li Y W. et al;《Tetrahedron》;20140520;第70卷;第4652-4656页 * |
| Ludovik N D. et al."Metal-Free Synthesis of 6‑Phosphorylated Phenanthridines: Synthetic and Mechanistic Insights".《Org. Lett》.2016,第18卷第5900-5903页. * |
| Zhang B. et al."6‑Phosphorylated Phenanthridines from 2‑Isocyanobiphenyls via Radical C−P and C−C Bond Formation".《Org. Lett》.2013,第16卷第250-253页. * |
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