CN109438349A - 6-(α-氰基亚胺)基菲啶类化合物及其合成方法 - Google Patents
6-(α-氰基亚胺)基菲啶类化合物及其合成方法 Download PDFInfo
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- CN109438349A CN109438349A CN201811072379.1A CN201811072379A CN109438349A CN 109438349 A CN109438349 A CN 109438349A CN 201811072379 A CN201811072379 A CN 201811072379A CN 109438349 A CN109438349 A CN 109438349A
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- methyl
- hydrogen
- dihydrophenanthridine
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- phenanthridines
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- -1 alpha-cyano imines Chemical class 0.000 title claims abstract description 61
- 238000010189 synthetic method Methods 0.000 title description 6
- 238000006243 chemical reaction Methods 0.000 claims abstract description 52
- 238000000034 method Methods 0.000 claims abstract description 31
- 239000002994 raw material Substances 0.000 claims abstract description 18
- 150000001875 compounds Chemical class 0.000 claims abstract description 11
- FAGLEPBREOXSAC-UHFFFAOYSA-N tert-butyl isocyanide Chemical compound CC(C)(C)[N+]#[C-] FAGLEPBREOXSAC-UHFFFAOYSA-N 0.000 claims abstract description 3
- CZKMPDNXOGQMFW-UHFFFAOYSA-N chloro(triethyl)germane Chemical compound CC[Ge](Cl)(CC)CC CZKMPDNXOGQMFW-UHFFFAOYSA-N 0.000 claims abstract 2
- 239000012043 crude product Substances 0.000 claims description 30
- 229910052739 hydrogen Inorganic materials 0.000 claims description 25
- 239000001257 hydrogen Substances 0.000 claims description 25
- 239000002904 solvent Substances 0.000 claims description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 21
- 150000002431 hydrogen Chemical group 0.000 claims description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 239000000460 chlorine Substances 0.000 claims description 11
- 239000000047 product Substances 0.000 claims description 10
- 239000000758 substrate Substances 0.000 claims description 9
- YQQRKUQVFWYEPV-UHFFFAOYSA-N 5,6-dihydrophenanthridine Chemical compound C1=CC=C2CNC3=CC=CC=C3C2=C1 YQQRKUQVFWYEPV-UHFFFAOYSA-N 0.000 claims description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical compound C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 claims description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 239000011737 fluorine Substances 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 claims description 6
- 235000011152 sodium sulphate Nutrition 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- 239000012065 filter cake Substances 0.000 claims description 4
- 239000000706 filtrate Substances 0.000 claims description 4
- 238000001914 filtration Methods 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- WHQSYGRFZMUQGQ-UHFFFAOYSA-N n,n-dimethylformamide;hydrate Chemical compound O.CN(C)C=O WHQSYGRFZMUQGQ-UHFFFAOYSA-N 0.000 claims description 4
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 claims description 4
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- TWBPWBPGNQWFSJ-UHFFFAOYSA-N 2-phenylaniline Chemical compound NC1=CC=CC=C1C1=CC=CC=C1 TWBPWBPGNQWFSJ-UHFFFAOYSA-N 0.000 claims description 3
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 3
- 238000006467 substitution reaction Methods 0.000 claims description 3
- AOPBDRUWRLBSDB-UHFFFAOYSA-N 2-bromoaniline Chemical compound NC1=CC=CC=C1Br AOPBDRUWRLBSDB-UHFFFAOYSA-N 0.000 claims description 2
- VPIDANAIZIMNGX-UHFFFAOYSA-N 4-methyl-n-(2-phenylphenyl)benzenesulfonamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC1=CC=CC=C1C1=CC=CC=C1 VPIDANAIZIMNGX-UHFFFAOYSA-N 0.000 claims description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 claims description 2
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 2
- JXASPPWQHFOWPL-UHFFFAOYSA-N Tamarixin Natural products C1=C(O)C(OC)=CC=C1C1=C(OC2C(C(O)C(O)C(CO)O2)O)C(=O)C2=C(O)C=C(O)C=C2O1 JXASPPWQHFOWPL-UHFFFAOYSA-N 0.000 claims description 2
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 2
- KDKYADYSIPSCCQ-UHFFFAOYSA-N ethyl acetylene Natural products CCC#C KDKYADYSIPSCCQ-UHFFFAOYSA-N 0.000 claims description 2
- 239000012074 organic phase Substances 0.000 claims description 2
- 238000000746 purification Methods 0.000 claims description 2
- 238000010791 quenching Methods 0.000 claims description 2
- 230000000171 quenching effect Effects 0.000 claims description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- YJXGADCZMLHGLV-UHFFFAOYSA-N aniline;pyridine Chemical compound C1=CC=NC=C1.NC1=CC=CC=C1 YJXGADCZMLHGLV-UHFFFAOYSA-N 0.000 claims 1
- 150000004054 benzoquinones Chemical class 0.000 claims 1
- 150000001721 carbon Chemical class 0.000 claims 1
- 238000002156 mixing Methods 0.000 claims 1
- 238000002360 preparation method Methods 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 238000003756 stirring Methods 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 238000006555 catalytic reaction Methods 0.000 abstract description 3
- RDOWQLZANAYVLL-UHFFFAOYSA-N phenanthridine Chemical group C1=CC=C2C3=CC=CC=C3C=NC2=C1 RDOWQLZANAYVLL-UHFFFAOYSA-N 0.000 abstract description 3
- 125000004093 cyano group Chemical group *C#N 0.000 abstract description 2
- 230000009257 reactivity Effects 0.000 abstract description 2
- 238000009776 industrial production Methods 0.000 abstract 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 16
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 12
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- 150000008422 chlorobenzenes Chemical class 0.000 description 9
- 239000002024 ethyl acetate extract Substances 0.000 description 9
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 9
- 239000003208 petroleum Substances 0.000 description 9
- 238000004809 thin layer chromatography Methods 0.000 description 9
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical class ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 8
- 238000001035 drying Methods 0.000 description 8
- 150000002825 nitriles Chemical class 0.000 description 8
- 150000005053 phenanthridines Chemical class 0.000 description 6
- QRUBYZBWAOOHSV-UHFFFAOYSA-M silver trifluoromethanesulfonate Chemical class [Ag+].[O-]S(=O)(=O)C(F)(F)F QRUBYZBWAOOHSV-UHFFFAOYSA-M 0.000 description 6
- 239000002585 base Substances 0.000 description 5
- 239000012266 salt solution Substances 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- WDQPRBKCNORRAR-UHFFFAOYSA-N [Ag].CS(=O)(=O)O.[F] Chemical compound [Ag].CS(=O)(=O)O.[F] WDQPRBKCNORRAR-UHFFFAOYSA-N 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 2
- 125000004494 ethyl ester group Chemical group 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 229910052709 silver Inorganic materials 0.000 description 2
- 239000004332 silver Substances 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- JXQCQIISNNKKIM-UHFFFAOYSA-N 1-bromo-5,6-dihydrophenanthridine Chemical compound Brc1cccc2NCc3ccccc3-c12 JXQCQIISNNKKIM-UHFFFAOYSA-N 0.000 description 1
- 238000004293 19F NMR spectroscopy Methods 0.000 description 1
- LXIBSKNXNJFKLV-UHFFFAOYSA-N 2,8-dimethyl-5-(4-methylphenyl)sulfonyl-6H-phenanthridine Chemical class CC1=CC=2C3=CC=C(C=C3CN(C=2C=C1)S(=O)(=O)C1=CC=C(C)C=C1)C LXIBSKNXNJFKLV-UHFFFAOYSA-N 0.000 description 1
- UKSYXZYABRTUDD-UHFFFAOYSA-N 3,8-dimethyl-5-(4-methylphenyl)sulfonyl-6H-phenanthridine Chemical class CC=1C=CC=2C3=CC=C(C=C3CN(C=2C=1)S(=O)(=O)C1=CC=C(C)C=C1)C UKSYXZYABRTUDD-UHFFFAOYSA-N 0.000 description 1
- QWCVBPUIUAMWMF-UHFFFAOYSA-N 5-(4-methylphenyl)sulfonyl-6h-phenanthridine Chemical class C1=CC(C)=CC=C1S(=O)(=O)N1C2=CC=CC=C2C2=CC=CC=C2C1 QWCVBPUIUAMWMF-UHFFFAOYSA-N 0.000 description 1
- QWYRPZNEEHFRFS-UHFFFAOYSA-N 8-methyl-5-(4-methylphenyl)sulfonyl-6H-phenanthridine Chemical class CC=1C=C2CN(C=3C=CC=CC=3C2=CC=1)S(=O)(=O)C1=CC=C(C)C=C1 QWYRPZNEEHFRFS-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000234479 Narcissus Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000006254 arylation reaction Methods 0.000 description 1
- 102000055104 bcl-X Human genes 0.000 description 1
- 108700000711 bcl-X Proteins 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 238000000375 direct analysis in real time Methods 0.000 description 1
- 238000012063 dual-affinity re-targeting Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- SEACYXSIPDVVMV-UHFFFAOYSA-L eosin Y Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C([O-])=C(Br)C=C21 SEACYXSIPDVVMV-UHFFFAOYSA-L 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 150000002527 isonitriles Chemical class 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 1
- 239000003504 photosensitizing agent Substances 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 238000007348 radical reaction Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/06—Ring systems of three rings
- C07D221/10—Aza-phenanthrenes
- C07D221/12—Phenanthridines
-
- 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
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
- C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明涉及一种α‑氰基亚胺取代的菲啶类化合物,该化合物的结构式为:
Description
技术领域
本发明涉及一种6-(α-氰基亚胺)基菲啶类化合物及其合成方法。
背景技术
菲啶类化合物是一类非常有价值的有机化合物,广泛存在于天然产物中。因其具有较好的生物活性及光电活性而被广泛应用于药物化学及有机功能材料领域中。例如,Shamma等人从多种植物中提取到了近百种含菲啶骨架的天然产物(见参考文献:Shamma,M.et al,J.Nat.Prod.1984,47,1)。Bastida等人从阿斯图里亚斯水仙中提取到了含有菲啶骨架的化合物Trisphaeridin(见参考文献:Bastida,J.et al,Planta Med.1997,63,583)。Chai等人合成了多种白屈菜红碱的类似物并测试了其对Bcl-XL和Bak肽的抑制活性,结果表明有三种新化合物均显示出更高的抑制活性(见参考文献:Chai,C.L.L.et al,J.Med.Chem.2008,51,6699)。LaVoie等人合成了一系列具有抗肿瘤活性的菲啶类化合物并对其细胞毒性进行了一系列的研究(见参考文献:LaVoie,E.J.et al,Bioorg.Med.Chem.2005,13,6782)。Turro等人合成了一种含有菲啶骨架的新型荧光探针并研究了其在细胞成像领域的应用(见参考文献:Turro,N.J.et al,J.Am.Chem.Soc.2008,130,7182)。Lakowicz等人合成了一种含有菲啶骨架的聚合物,该聚合物可以显著提高其在440nm波长处的等离子体吸收率(见参考文献:Lakowicz,J.R.J.Phys.Chem.B2005,109,8701)。
综上所述,菲啶类化合物是及其重要的化合物,近一百年来,科学家们对菲啶类化合物的合成进行了很多的研究。文献中报道过的合成菲啶类化合物的方法主要有以下几种:
(一)Pictet等人以2-苯基苯胺类化合物为原料在氯化锌参与下与芳基甲酸反应,得到了一系列的6-芳基菲啶类化合物(见参考文献:Pictet et al,Chem.Ber.1896,29,1191)。
(二)Gilman等人直接以菲啶为底物,以苯基锂为芳基化试剂,实现了菲啶的直接芳基化。但该方法的官能团兼容性较差(见参考文献:Nelson.etal,J.Am.Chem.Soc.1948,70,3316)。
(三)Nanni等人以联苯基异腈为原料,在自由基反应条件下发生了自由基串联环化反应,构建了6-取代的菲啶类化合物(见参考文献:Nanni,D.et al,Terahedron1995,51,9045)。该方法经Chatani等人的系统研究后,成为高效构建6-取代的菲啶类化合物的一种重要方法(见参考文献:Chatani,N.et al,Angew.Chem.Int.Ed.2012,51,11363)。
(四)李斌等人报道了从三取代亚胺类化合物出发,在醋酸钯的催化下,以碳酸铯为碱,经碳-氢键活化反应构建了6-芳基菲啶类化合物(见参考文献:Li,B.et al,J.Org.Chem.2011,76,9507)。
(五)刘绪宗等人利用联苯基重氮盐与氰基化合物的反应,在无金属催化的条件下,构建了6-取代菲啶类化合物。该方法中,氰基化合物作为溶剂参与了反应,因此在有机合成应用中受到很大限制(见参考文献:Liu,S.et al,J.Org.Chem.2015,80,5329)。
(六)郭丽娜等人报道了联苯基乙烯基叠氮类化合物在以曙红Y作为光敏剂的条件下,可与N-酰氧基邻苯二甲酰亚胺产生的自由基发生串联环化反应,构建了6-取代菲啶类化合物(见参考文献:Guo,L.et al,J.Org.Chem.2018,83,1598)。
目前菲啶类化合物的合成方法主要有以上几种,但是上述方法可以合成的化合物类型仍较为有限,对于一些带有特殊取代基的化合物仍需发展新的合成方法。
发明内容
本发明的目的之一在于提供一种6-(α-氰基亚胺)基菲啶类化合物。
本发明的目的之二在于提供该化合物的合成方法。
为达到上述目的,本发明方法采用的反应机理为:
其中:R1为氢,甲基,溴,苯基或(三甲基硅基)乙炔基;
R2为氢,甲基;
R3为氢,甲基,氟,氯。
根据上述反应机理,本发明采用了如下的技术方案:
一种6-(α-氰基亚胺)基菲啶类化合物,其特征在于该化合物的结构式为:
其中:R1为氢、甲基、溴、苯基或(三甲基硅基)乙炔基;
R2为氢或甲基;
R3为氢、甲基、氟或氯。
一种制备所述的5,6-二氢菲啶的方法,其特征在于该方法具有如下步骤:在惰性气氛下,将邻溴苯胺、苯硼酸、碳酸钾、双三苯基膦二氯化钯按1.0:1.2:4.0:0.05的摩尔比加入到水和N,N-二甲基甲酰胺以体积比1.0:4.0混合的溶剂中,于80℃搅拌反应至反应原料消失。反应结束后,冷至室温,用硅藻土过滤反应液,并用乙酸乙酯洗涤滤饼。滤液依次用水和饱和氯化钠溶液洗涤,并用硫酸钠干燥。减压除去溶剂后得粗产物;该粗产物经分离提纯得到2-苯基苯胺,其具有如下结构:
其中:R1为氢、甲基或溴;
R2为氢或甲基;
R3为氢、甲基、氟或氯。
向吡啶中加入上述2-苯基苯胺与对甲苯磺酰氯(摩尔比为1.0:1.2),60℃反应12小时。减压除去吡啶,用二氯甲烷溶解残余物,并依次用浓度为2.0mol/L的盐酸溶液、饱和碳酸钠溶液、饱和氯化钠溶液洗涤有机相,用硫酸钠干燥。减压除去溶剂,得到N-对甲苯磺酰基-2-苯基苯胺,其具有如下结构:
其中:R1为氢、甲基或溴;
R2为氢或甲基;
R3为氢、甲基、氟或氯。
将上述N-对甲苯磺酰基-2-苯基苯胺加入到硫酸:乙酸以体积比1.0:(4.0~10.0)混合的溶剂中,室温反应12小时。加入水淬灭,过滤并收集残余物。该残余物经分离提纯即得到所述5,6-二氢菲啶。
一种制备所述的苯基或(三甲基硅基)乙炔基取代5,6-二氢菲啶的方法,其特征在于该方法具有如下步骤:在惰性气氛下,将N-对甲苯磺酰基-8-溴-5,6-二氢菲啶(其结构式为:)、苯硼酸,碳酸钾、双三苯基膦二氯化钯按1.0:1.2:4.0:0.05的摩尔比加入到水和N,N-二甲基甲酰胺以体积比1.0:4.0混合的溶剂中,于80℃搅拌反应至反应原料消失。反应结束后,冷至室温,用硅藻土过滤反应液,并用二氯甲烷洗涤滤饼。滤液依次用水和饱和氯化钠溶液洗涤,并用硫酸钠干燥。减压除去溶剂后得粗产物;该粗产物经分离提纯得到所述的苯基取代的5,6-二氢菲啶,其结构式为或者在惰性气氛下,N-对甲苯磺酰基-8-溴-5,6-二氢菲啶(其结构式为:)、醋酸钯、碘化亚铜、三甲基硅基乙炔按1.0:0.05:0.05:3.0的摩尔比加入到三乙胺中,90℃反应至原料消失;反应结束后,冷至室温,除去溶剂后得粗产物;该粗产物经分离提纯,即得到所述的(三甲基硅基)乙炔基取代的5,6-二氢菲啶,其结构式为
本发明方法原料简单易得,并采用叔丁基异腈作为反应的氰基源,在三氟甲磺酸银的催化下展现出较高的反应活性;反应过程中操作简单,条件温和,环境友好,产率一般到中等。氰基亚胺这一特殊官能团可通过一系列化学方法,转化为酰胺(见参考文献:Zhu,J.P.et al,Chem.Eur.J.2012,18,14812),杂环化合物(见参考文献:Zhao,Y.L.et al,Org.Biomol.Chem.2016,14,165),羧酸及羧酸酯(见参考文献:Stevens,E.et al,TerahedronLett.2002,43,5361)。因此,该方法具有良好的应用前景。
具体实施方式
实施例一:(Z)-N-(叔丁基)菲啶-6-甲亚胺氰化物
(Z)-N-(叔丁基)菲啶-6-甲亚胺氰化物采用下述步骤:①在1000毫升反应釜中加入15.9克N-对甲苯磺酰基-5,6-二氢菲啶,20.1毫升叔丁基异腈,1.74克三氟甲磺酸银,30.6克2,3-二氯-5,6-二氰基-1,4-苯醌,675毫升氯代苯,加热至80℃。用薄层层析方法跟踪反应,至反应原料消失;②反应结束后,乙酸乙酯萃取产物,饱和食盐水分别洗涤,干燥后用旋转蒸发仪去掉溶剂,得粗产物;③粗产物用柱层析(石油醚:乙酸乙酯=20:1)纯化,得到8.8克(Z)-N-(叔丁基)菲啶-6-甲亚胺氰化物,其结构式为:产率为68%。熔点:103-105℃。
IR(KBr,cm-1):3075,2975,2217,1612,1450,1362,1207,937;
1H NMR(CDCl3,500MHz):δ9.10(d,J=8.4Hz,1H),8.69(d,J=8.3Hz,1H),8.60(d,J=7.8Hz,1H),8.31(d,J=7.8Hz,1H),7.89(t,J=7.4Hz,1H),7.83-7.74(m,2H),7.72(t,J=7.4Hz,1H,),1.70(s,9H);
13C NMR(CDCl3,125MHz):δ151.44,142.74,139.05,134.01,131.09,131.05,129.22,128.97,128.05,127.73,124.81,123.82,122.38,122.12,112.44,59.94,29.41;
LC-MS(ESI)m/z:288.1[M+H]+;
HRMS(DART Positive)m/z:calcd for C19H17N3[M+H]+288.1492,found288.1495
实施例二:(Z)-N-(叔丁基)-8-甲基菲啶-6-甲亚胺氰化物
(Z)-N-(叔丁基)-8-甲基菲啶-6-甲亚胺氰化物采用下述步骤:①在1000毫升反应釜中加入15.6克N-对甲苯磺酰基-5,6-二氢-8-甲基菲啶,25.2毫升叔丁基异腈,1.74克三氟甲磺酸银,15.9克2,3-二氯-5,6-二氰基-1,4-苯醌,450毫升氯代苯,加热至90℃。用薄层层析方法跟踪反应,至反应原料消失;②反应结束后,乙酸乙酯萃取产物,饱和食盐水分别洗涤,干燥后用旋转蒸发仪去掉溶剂,得粗产物;③粗产物用柱层析(石油醚:乙酸乙酯=20:1)纯化,得到7.18克(Z)-N-(叔丁基)-8-甲基菲啶-6-甲亚胺氰化物,其结构式为:产率为53%。熔点:158-160℃。
IR(KBr,cm-1):2965.9,2208.3,1954.4,1741.1,1621.8,1568.0,1459.3,1366.4,1234.9;
1H NMR(CDCl3,500MHz):δ8.90(s,1H),8.59-8.50(m,2H),8.31-8.25(m,1H),7.80-7.68(m,3H),2.59(s,3H),1.71(s,9H);
13C NMR(CDCl3,125MHz):δ151.10,142.79,139.03 138.06,132.76,131.95,131.02,128.88,128.76,127.18,124.93,123.97,122.28,121.95,112.45,59.94,29.40,22.18;
LC-MS(EI)m/z:301.2[M]+;
HRMS(EI)m/z:calcd for C20H19N3[M]+301.1579,found 301.1584.
实施例三:(Z)-8-溴-N-(叔丁基)菲啶-6-甲亚胺氰化物
(Z)-N-(叔丁基)-8-溴菲啶-6-甲亚胺氰化物采用下述步骤:①在1000毫升反应釜中加入18.6克N-对甲苯磺酰基-5,6-二氢-8-溴菲啶,20.1毫升叔丁基异腈,1.74克三氟甲磺酸银,30.6克2,3-二氯-5,6-二氰基-1,4-苯醌,450毫升氯代苯,加热至85℃。用薄层层析方法跟踪反应,至反应原料消失;②反应结束后,乙酸乙酯萃取产物,饱和食盐水分别洗涤,干燥后用旋转蒸发仪去掉溶剂,得粗产物;③粗产物用柱层析(石油醚:乙酸乙酯=20:1)纯化,得到5.18克(Z)-N-(叔丁基)-8-甲基菲啶-6-甲亚胺氰化物,其结构式为:产率为31%。熔点:172-174℃。
IR(KBr,cm-1):2967.0,2931.7,2220.7,1614.3,1692.6,1616.6,1566.5;
1H NMR(CDCl3,500MHz):δ9.47(d,J=2.0Hz,1H),8.56-8.47(m,2H),8.30(dd,J=8.2,1.2Hz,1H),7.95(dd,J=8.8,2.0Hz,1H),7.84-7.79(m,1H),7.79-7.74(m,1H),1.71(s,9H);
13C NMR(CDCl3,125MHz):δ149.67,142.66,139.10,134.17,132.64,131.33,130.68,129.65,129.52,124.96,124.32,124.08,122.43,121.97,112.08,60.13,29.34;
LC-MS(ESI)m/z:366.1[M(79Br)+H]+(81),368.1[M(81Br)+H]+(100);
HRMS(ESI)m/z:calcd for C19H17N3Br[M+H]+366.0600,found 366.0601.
实施例四:(Z)-N-(叔丁基)-8-苯基菲啶-6-甲亚胺氰化物
(Z)-N-(叔丁基)-8-苯基菲啶-6-甲亚胺氰化物采用下述步骤:①在1000毫升反应釜中加入18.5克N-对甲苯磺酰基-5,6-二氢-8-苯基菲啶,25.2毫升叔丁基异腈,1.74克三氟甲磺酸银,40.9克2,3-二氯-5,6-二氰基-1,4-苯醌,450毫升氯代苯,加热至90℃。用薄层层析方法跟踪反应,至反应原料消失;②反应结束后,乙酸乙酯萃取产物,饱和食盐水分别洗涤,干燥后用旋转蒸发仪去掉溶剂,得粗产物;③粗产物用柱层析(石油醚:乙酸乙酯=20:1)纯化,得到5.78克(Z)-N-(叔丁基)-8-苯基菲啶-6-甲亚胺氰化物,其结构式为:产率为36%。熔点:112-114℃。
IR(KBr,cm-1):2965.7,2859.4,2216.6,1608.8,1463.4,1395.9;
1H NMR(CDCl3,500MHz):δ9.55(d,J=1.3Hz,1H),8.70(d,J=8.7Hz,1H),8.58(d,J=7.7Hz,1H),8.31(d,J=7.5Hz,1H),8.13(dd,J=8.6,1.5Hz,1H),7.82-7.72(m,4H),7.54(t,J=7.7Hz,2H),7.44(t,J=7.4Hz,1H),1.73(s,9H);
13C NMR(CDCl3,125MHz):δ151.15,142.71,140.56,140.41,139.40,132.97,131.16,129.97,129.26,129.18,129.14,128.07,127.38,126.05,124.67,124.27,122.94,122.14,112.32,59.90,29.43;
LC-MS(EI)m/z:363.2[M+];
HRMS(ESI)m/z:calcd for C25H21N3[M]+363.1735,found 363.1736.
实施例五:(Z)-N-(叔丁基)-8-((三甲基甲硅基)乙炔基)菲啶-6-甲亚胺氰化物
(Z)-N-(叔丁基)-8-((三甲基甲硅基)乙炔基)菲啶-6-甲亚胺氰化物采用下述步骤:①在1000毫升反应釜中加入19.4克N-对甲苯磺酰基-5,6-二氢-8-(三甲基甲硅基)乙炔基)菲啶,25.2毫升叔丁基异腈,1.74克三氟甲磺酸银,15.9克2,3-二氯-5,6-二氰基-1,4-苯醌,450毫升氯代苯,加热至80℃。用薄层层析方法跟踪反应,至反应原料消失;②反应结束后,乙酸乙酯萃取产物,饱和食盐水分别洗涤,干燥后用旋转蒸发仪去掉溶剂,得粗产物;③粗产物用柱层析(石油醚:乙酸乙酯=20:1)纯化,得到7.18克(Z)-N-(叔丁基)-8-甲基菲啶-6-甲亚胺氰化物,其结构式为:产率为53%。熔点:135-137℃。
IR(KBr,cm-1):2966.6,2150.3,1690.5,1647.2,1619.5,1465.2,1363.4;
1H NMR(CDCl3,500MHz):δ9.36(d,J=1.4Hz,1H),8.59(d,J=8.6Hz,1H),8.55(d,J=7.9Hz,1H),8.30(dd,J=8.2,1.3Hz,1H),7.89(dd,J=8.6,1.7Hz,1H),7.84-7.72(m,2H),1.71(s,9H),0.30(s,9H);
13C NMR(CDCl3,125MHz):δ150.40,142.88,138.78,133.38,133.35,132.13,131.10,129.51,129.15,124.29,123.43,122.86,122.25,122.21,112.05,104.63,96.30,59.96,29.17,-0.11;
LC-MS(EI)m/z:383.2[M]+;
HRMS(ESI)m/z:calcd for C24H25N3Si[M]+383.1818,found 383.1815
实施例六:(Z)-N-(叔丁基)-3,8-二甲基菲啶-6-甲亚胺氰化物
(Z)-N-(叔丁基)-3,8-二甲基菲啶-6-甲亚胺氰化物采用下述步骤:①在1000毫升反应釜中加入16.3克N-对甲苯磺酰基-5,6-二氢-3,8-二甲基菲啶,25.2毫升叔丁基异腈,1.74克三氟甲磺酸银,15.9克2,3-二氯-5,6-二氰基-1,4-苯醌,450毫升氯代苯,加热至80℃。用薄层层析方法跟踪反应,至反应原料消失;②反应结束后,乙酸乙酯萃取产物,饱和食盐水分别洗涤,干燥后用旋转蒸发仪去掉溶剂,得粗产物;③粗产物用柱层析(石油醚:乙酸乙酯=20:1)纯化,得到6.93克(Z)-N-(叔丁基)-3,8-二甲基菲啶-6-甲亚胺氰化物,其结构式为:产率为49%。熔点:158-160℃。
IR(KBr,cm-1):2970.1,2909.2,2212.4,1619.9,1565.2,1470.6;
1H NMR(CDCl3,500MHz):δ8.89(s,1H),8.52(d,J=8.5Hz,1H),8.43(d,J=8.4Hz,1H),8.09(s,1H),8.68(dd,J=8.5,1.6Hz,1H),7.56(dd,J=8.4,1.6Hz,1H),2.60(s,3H),2.57(s,3H),1.70(s,9H);
13C NMR(CDCl3,125MHz):δ151.06,142.64,139.17,138.98,137.53,132.69,132.04,130.72,130.46,127.11,123.70,122.64,122.10,121.73,112.50,59.87,29.41,22.16,21.55;
LC-MS(EI)m/z:315.2[M]+;
HRMS(EI)m/z:calcd for C21H21N3[M]+315.1735,found 315.1738.
实施例七:(Z)-N-(叔丁基)-3-氟-8-甲基菲啶-6-甲亚胺氰化物
(Z)-N-(叔丁基)-3-氟-8-甲基菲啶-6-甲亚胺氰化物采用下述步骤:①在1000毫升反应釜中加入16.5克N-对甲苯磺酰基-5,6-二氢-3-氟-8-甲基菲啶,20.1毫升叔丁基异腈,1.74克三氟甲磺酸银,30.6克2,3-二氯-5,6-二氰基-1,4-苯醌,675毫升氯代苯,加热至80℃。用薄层层析方法跟踪反应,至反应原料消失;②反应结束后,乙酸乙酯萃取产物,饱和食盐水分别洗涤,干燥后用旋转蒸发仪去掉溶剂,得粗产物;③粗产物用柱层析(石油醚:乙酸乙酯=20:1)纯化,得到6.65克(Z)-N-(叔丁基)-3-氟-8-甲基菲啶-6-甲亚胺氰化物,其结构式为:产率为46%。熔点:161-163℃。
IR(KBr,cm-1):2966.8,2927.6,2220.2,1620.7,1575.9,1472.7;
1H NMR(CDCl3,500MHz):δ8.82(s,1H),8.48(dd,J=9.1,5.7Hz,1H),8.44(d,J=8.4Hz,1H),7.90(dd,J=9.5,2.5Hz,1H),7.68(d,J=8.3Hz,1H),7.46(td,J=8.2,1.8Hz,1H),2.57(s,3H),1.71(s,9H);
19F NMR(CDCl3,470MHz):δ-111.94(m,Ar-F);
13C NMR(CDCl3,125MHz):δ162.59(d,1JC-F=249.0Hz),152.24,143.55(d,3JC-F=12.0Hz),138.67,137.89,133.14,131.78,127.22,123.89(d,3JC-F=9.3Hz),123.48,122.03,121.60(d,4JC-F=2.2Hz),117.98(d,2JC-F=24.0Hz),115.17(d,2JC-F=20.7Hz),112.30,60.09,29.38,22.12;
LC-MS(EI)m/z:319.2[M]+;
HRMS(ESI)m/z:calcd for C20H18N3F[M]+319.1485,found 319.1484.
实施例八:(Z)-N-(叔丁基)-3-氯-8-甲基菲啶-6-甲亚胺氰化物
(Z)-N-(叔丁基)-3-氯-8-甲基菲啶-6-甲亚胺氰化物采用下述步骤:①在1000毫升反应釜中加入17.3克N-对甲苯磺酰基-5,6-二氢-3-氯-8-甲基菲啶,20.1毫升叔丁基异腈,1.74克三氟甲磺酸银,30.6克2,3-二氯-5,6-二氰基-1,4-苯醌,675毫升氯代苯,加热至80℃。用薄层层析方法跟踪反应,至反应原料消失;②反应结束后,乙酸乙酯萃取产物,饱和食盐水分别洗涤,干燥后用旋转蒸发仪去掉溶剂,得粗产物;③粗产物用柱层析(石油醚:乙酸乙酯=20:1)纯化,得到6.99克(Z)-N-(叔丁基)-3-氯-8-甲基菲啶-6-甲亚胺氰化物,其结构式为:产率为46%。熔点:206-208℃。
IR(KBr,cm-1):2966.4,2923.7,2218.4,1614.3,1466.8,1365.1;
1H NMR(CDCl3,500MHz):δ8.82(s,1H),8.40(d,J=8.5Hz,1H),8.36(d,J=8.8Hz,1H),8.20(d,J=2.0Hz,1H),7.67(dd,J=8.4,1.0Hz,1H),7.61(dd,J=8.8,2.1Hz,1H),2.57(s,3H),1.71(s,9H);
13C NMR(CDCl3,125MHz):δ152.00,142.87,138.68,138.39,134.35,133.10,131.44,129.87,129.24,127.26,123.75,123.25,123.24,122.09,112.25,60.08,29.36,22.17;
LC-MS(EI)m/z:337.1(7)[M(37Cl)]+,335.1(21)[M(35Cl)]+;
HRMS(ESI)m/z:calcd for C20H18N3Cl[M]+335.1189,found 335.1183.
实施例九:(Z)-N-(叔丁基)-2,8-二甲基菲啶-6-甲亚胺氰化物
(Z)-N-(叔丁基)-2,8-二甲基菲啶-6-甲亚胺氰化物采用下述步骤:①在1000毫升反应釜中加入16.3克N-对甲苯磺酰基-5,6-二氢-2,8-二甲基菲啶,25.2毫升叔丁基异腈,1.74克三氟甲磺酸银,15.9克2,3-二氯-5,6-二氰基-1,4-苯醌,450毫升氯代苯,加热至85℃。用薄层层析方法跟踪反应,至反应原料消失;②反应结束后,乙酸乙酯萃取产物,饱和食盐水分别洗涤,干燥后用旋转蒸发仪去掉溶剂,得粗产物;③粗产物用柱层析(石油醚:乙酸乙酯=20:1)纯化,得到4.37克(Z)-N-(叔丁基)-2,8-二甲基菲啶-6-甲亚胺氰化物,其结构式为:产率为31%。熔点:138-140℃。
IR(KBr,cm-1):2970.6,2915.2,2212.4,1899.3,1743.5,1609.2,1567.8,1462.8,1233.3,1200.3;
1H NMR(CDCl3,500MHz):δ8.91(s,1H),8.52(d,J=8.5Hz,1H),8.30(s,1H),8.16(d,J=8.3Hz,1H),7.67(d,J=8.4Hz,1H),7.57(d,J=8.3Hz,1H),2.64(s,3H),2.57(s,3H),1.71(s,9H);
13C NMR(CDCl3,125MHz):δ150.13,140.85,139.22,139.14,137.87,132.48,131.60,130.75,130.55,127.10,124.77,124.06,122.22,121.55,112.51,59.80,29.40,22.35,22.17;
LC-MS(EI)m/z:315.2[M]+;
HRMS(EI)m/z:calcd for C21H21N3[M]+315.1735,found 315.1738。
Claims (5)
1.一种6-(α-氰基亚胺)基菲啶类化合物,其特征在于该化合物的结构式为:
其中:R1为氢、甲基、溴、苯基或(三甲基硅基)乙炔基;
R2为氢或甲基;
R3为氢、甲基、氟或氯。
2.一种权利要求1所述的6-(α-氰基亚胺)基菲啶类化合物的制备方法,其特征在于该方法具有如下步骤:在惰性气氛下,将5,6-二氢菲啶、叔丁基异腈、三氟甲磺酸银、二氯二氰基苯醌(DDQ)按1.0:(4.0~5.0):(0.1~0.2):(3.0~4.0)的摩尔比加入到氯代苯溶剂中,回流搅拌反应至反应原料消失;反应结束后,冷至室温,除去溶剂后得粗产物;该粗产物经分离提纯,即得到取代的6-(α-氰基亚胺)基菲啶类化合物;所述的5,6-二氢菲啶的结构式为:
其中:R1为氢、甲基、溴、苯基或(三甲基硅基)乙炔基;
R2为氢或甲基;
R3为氢、甲基、氟或氯。
3.一种权利要求2所述的5,6-二氢菲啶的方法,其特征在于该方法具有如下步骤:在惰性气氛下,将邻溴苯胺、苯硼酸、碳酸钾、双三苯基膦二氯化钯按1.0:1.2:4.0:0.05的摩尔比加入到水和N,N-二甲基甲酰胺以体积比1.0:4.0混合的溶剂中,于80℃搅拌反应至反应原料消失。反应结束后,冷至室温,用硅藻土过滤反应液,并用乙酸乙酯洗涤滤饼。滤液依次用水和饱和氯化钠溶液洗涤,并用硫酸钠干燥。减压除去溶剂后得粗产物;该粗产物经分离提纯得到2-苯基苯胺,其具有如下结构:
其中:R1为氢、甲基或溴;
R2为氢或甲基;
R3为氢、甲基、氟或氯。
4.一种权利要求2所述的5,6-二氢菲啶的方法,其特征在于:向吡啶中加入上述2-苯基苯胺与对甲苯磺酰氯(摩尔比为1.0:1.2),60℃反应12小时。
减压除去吡啶,用二氯甲烷溶解残余物,并依次用浓度为2.0mol/L的盐酸溶液、饱和碳酸钠溶液、饱和氯化钠溶液洗涤有机相,用硫酸钠干燥。减压除去溶剂,得到N-对甲苯磺酰基-2-苯基苯胺,其具有如下结构:
其中:R1为氢、甲基或溴;
R2为氢或甲基;
R3为氢、甲基、氟或氯。
将上述N-对甲苯磺酰基-2-苯基苯胺加入到硫酸:乙酸以体积比1.0:(4.0~10.0)混合的溶剂中,室温反应12小时。加入水淬灭,过滤并收集残余物。该残余物经分离提纯即得到所述5,6-二氢菲啶。
5.一种制备权利要求2所述的苯基或(三甲基硅基)乙炔基取代5,6-二氢菲啶的方法,其特征在于该方法具有如下步骤:在惰性气氛下,将N-对甲苯磺酰基-8-溴-5,6-二氢菲啶(其结构式为:)、苯硼酸,碳酸钾、双三苯基膦二氯化钯按1.0:1.2:4.0:0.05的摩尔比加入到水和N,N-二甲基甲酰胺以体积比1.0:4.0混合的溶剂中,于80℃搅拌反应至反应原料消失。反应结束后,冷至室温,用硅藻土过滤反应液,并用二氯甲烷洗涤滤饼。滤液依次用水和饱和氯化钠溶液洗涤,并用硫酸钠干燥。减压除去溶剂后得粗产物;该粗产物经分离提纯得到所述的苯基取代的5,6-二氢菲啶,其结构式为或者在惰性气氛下,N-对甲苯磺酰基-8-溴-5,6-二氢菲啶(其结构式为:)、醋酸钯、碘化亚铜、三甲基硅基乙炔按1.0:0.05:0.05:3.0的摩尔比加入到三乙胺中,90℃反应至原料消失;反应结束后,冷至室温,除去溶剂后得粗产物;该粗产物经分离提纯,即得到所述的(三甲基硅基)乙炔基取代的5,6-二氢菲啶,其结构式为
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