CN114805163B - 一种有机硒化合物的合成方法 - Google Patents
一种有机硒化合物的合成方法 Download PDFInfo
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- CN114805163B CN114805163B CN202210502474.0A CN202210502474A CN114805163B CN 114805163 B CN114805163 B CN 114805163B CN 202210502474 A CN202210502474 A CN 202210502474A CN 114805163 B CN114805163 B CN 114805163B
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- oxime
- perfluorobenzoyl
- reaction
- diselenide
- organic
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- 229940065287 selenium compound Drugs 0.000 title claims abstract description 17
- 150000003343 selenium compounds Chemical class 0.000 title claims abstract description 16
- 238000000034 method Methods 0.000 title claims description 13
- 230000002194 synthesizing effect Effects 0.000 title claims description 6
- 238000006243 chemical reaction Methods 0.000 claims abstract description 104
- -1 oxime ester Chemical class 0.000 claims abstract description 96
- 239000003054 catalyst Substances 0.000 claims abstract description 10
- XIMIGUBYDJDCKI-UHFFFAOYSA-N diselenium Chemical compound [Se]=[Se] XIMIGUBYDJDCKI-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 99
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 96
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 68
- 150000002923 oximes Chemical class 0.000 claims description 45
- 239000003446 ligand Substances 0.000 claims description 37
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 34
- 239000000741 silica gel Substances 0.000 claims description 34
- 229910002027 silica gel Inorganic materials 0.000 claims description 34
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical group C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 32
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims description 32
- 239000003208 petroleum Substances 0.000 claims description 32
- HJDKCHUESYFUMG-UHFFFAOYSA-N cycloocta-1,5-diene;nickel Chemical compound [Ni].C1CC=CCCC=C1 HJDKCHUESYFUMG-UHFFFAOYSA-N 0.000 claims description 22
- YWWZCHLUQSHMCL-UHFFFAOYSA-N diphenyl diselenide Chemical group C=1C=CC=CC=1[Se][Se]C1=CC=CC=C1 YWWZCHLUQSHMCL-UHFFFAOYSA-N 0.000 claims description 18
- 229960002089 ferrous chloride Drugs 0.000 claims description 12
- KYGSYTRHCDNSGS-UHFFFAOYSA-N 1-phenylpent-4-en-1-one Chemical group C=CCCC(=O)C1=CC=CC=C1 KYGSYTRHCDNSGS-UHFFFAOYSA-N 0.000 claims description 7
- 239000003513 alkali Substances 0.000 claims description 7
- 239000007810 chemical reaction solvent Substances 0.000 claims description 6
- VLXBWPOEOIIREY-UHFFFAOYSA-N dimethyl diselenide Chemical compound C[Se][Se]C VLXBWPOEOIIREY-UHFFFAOYSA-N 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- 238000004440 column chromatography Methods 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
- SDLBMJQKOPWWGV-UHFFFAOYSA-N 1-fluoro-4-[(4-fluorophenyl)diselanyl]benzene Chemical compound C1=CC(F)=CC=C1[Se][Se]C1=CC=C(F)C=C1 SDLBMJQKOPWWGV-UHFFFAOYSA-N 0.000 claims description 3
- ZIXLDMFVRPABBX-UHFFFAOYSA-N 2-methylcyclopentan-1-one Chemical compound CC1CCCC1=O ZIXLDMFVRPABBX-UHFFFAOYSA-N 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 238000001308 synthesis method Methods 0.000 claims description 3
- IHFLMGMYVDKACS-UHFFFAOYSA-N 1-(3-chlorophenyl)pent-4-en-1-one Chemical compound ClC1=CC=CC(C(=O)CCC=C)=C1 IHFLMGMYVDKACS-UHFFFAOYSA-N 0.000 claims description 2
- RTMUTPLAEKUPML-UHFFFAOYSA-N 1-(3-methoxyphenyl)pent-4-en-1-one Chemical compound COC1=CC=CC(C(=O)CCC=C)=C1 RTMUTPLAEKUPML-UHFFFAOYSA-N 0.000 claims description 2
- WXEPXRKKIGTRHM-UHFFFAOYSA-N 1-(4-chlorophenyl)pent-4-en-1-one Chemical compound ClC1=CC=C(C(=O)CCC=C)C=C1 WXEPXRKKIGTRHM-UHFFFAOYSA-N 0.000 claims description 2
- IFCIFYPGYHSAOT-UHFFFAOYSA-N 1-(4-methoxyphenyl)pent-4-en-1-one Chemical compound COC1=CC=C(C(=O)CCC=C)C=C1 IFCIFYPGYHSAOT-UHFFFAOYSA-N 0.000 claims description 2
- OAPBYJHRDZXZDS-UHFFFAOYSA-N 1-(furan-2-yl)pent-4-en-1-one Chemical compound C=CCCC(=O)C1=CC=CO1 OAPBYJHRDZXZDS-UHFFFAOYSA-N 0.000 claims description 2
- RLDSFBXSHHFHGA-UHFFFAOYSA-N 1-methoxy-4-[(4-methoxyphenyl)diselanyl]benzene Chemical compound C1=CC(OC)=CC=C1[Se][Se]C1=CC=C(OC)C=C1 RLDSFBXSHHFHGA-UHFFFAOYSA-N 0.000 claims description 2
- KJCNOACMRYZZFR-UHFFFAOYSA-N 1-methyl-4-[(4-methylphenyl)diselanyl]benzene Chemical compound C1=CC(C)=CC=C1[Se][Se]C1=CC=C(C)C=C1 KJCNOACMRYZZFR-UHFFFAOYSA-N 0.000 claims description 2
- UMQJUMQJBPQOLL-UHFFFAOYSA-N 1-thiophen-2-ylpent-4-en-1-one Chemical compound C=CCCC(=O)C1=CC=CS1 UMQJUMQJBPQOLL-UHFFFAOYSA-N 0.000 claims description 2
- YQENJRQBTHILBT-UHFFFAOYSA-N 2-methylcyclobutan-1-one Chemical compound CC1CCC1=O YQENJRQBTHILBT-UHFFFAOYSA-N 0.000 claims description 2
- PVHNKILPLXXDDZ-UHFFFAOYSA-N 2-phenylcycloheptan-1-one Chemical compound O=C1CCCCCC1C1=CC=CC=C1 PVHNKILPLXXDDZ-UHFFFAOYSA-N 0.000 claims description 2
- 230000005526 G1 to G0 transition Effects 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- 238000000746 purification Methods 0.000 claims description 2
- HYAVEDMFTNAZQE-UHFFFAOYSA-N (benzyldiselanyl)methylbenzene Chemical compound C=1C=CC=CC=1C[Se][Se]CC1=CC=CC=C1 HYAVEDMFTNAZQE-UHFFFAOYSA-N 0.000 claims 1
- ROADCYAOHVSOLQ-UHFFFAOYSA-N 3-oxetanone Chemical compound O=C1COC1 ROADCYAOHVSOLQ-UHFFFAOYSA-N 0.000 claims 1
- NMCUIPGRVMDVDB-UHFFFAOYSA-L iron dichloride Chemical compound Cl[Fe]Cl NMCUIPGRVMDVDB-UHFFFAOYSA-L 0.000 claims 1
- 125000004122 cyclic group Chemical group 0.000 abstract description 5
- 150000002148 esters Chemical class 0.000 abstract description 5
- 229910052723 transition metal Inorganic materials 0.000 abstract description 5
- 150000003624 transition metals Chemical class 0.000 abstract description 5
- 238000010189 synthetic method Methods 0.000 abstract description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 abstract 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 abstract 2
- 239000002994 raw material Substances 0.000 abstract 2
- 150000001875 compounds Chemical class 0.000 abstract 1
- 125000004966 cyanoalkyl group Chemical group 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 229910052742 iron Inorganic materials 0.000 abstract 1
- 229910052759 nickel Inorganic materials 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 64
- 239000011261 inert gas Substances 0.000 description 60
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 30
- 238000005160 1H NMR spectroscopy Methods 0.000 description 30
- 238000002360 preparation method Methods 0.000 description 30
- ZUVVLBGWTRIOFH-UHFFFAOYSA-N methyl 4-methyl-2-[(4-methylphenyl)sulfonylamino]pentanoate Chemical compound COC(=O)C(CC(C)C)NS(=O)(=O)C1=CC=C(C)C=C1 ZUVVLBGWTRIOFH-UHFFFAOYSA-N 0.000 description 11
- 239000011669 selenium Substances 0.000 description 7
- KDZLXOUZKATOSA-UHFFFAOYSA-N 5-phenyl-2-(phenylselanylmethyl)-3,4-dihydro-2H-pyrrole Chemical compound C1CC(C=2C=CC=CC=2)=NC1C[Se]C1=CC=CC=C1 KDZLXOUZKATOSA-UHFFFAOYSA-N 0.000 description 6
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 6
- SHQSVMDWKBRBGB-UHFFFAOYSA-N cyclobutanone Chemical compound O=C1CCC1 SHQSVMDWKBRBGB-UHFFFAOYSA-N 0.000 description 6
- 229940091258 selenium supplement Drugs 0.000 description 6
- 229910052711 selenium Inorganic materials 0.000 description 5
- 238000001228 spectrum Methods 0.000 description 5
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 3
- QXCFWBGPRMYUTM-UHFFFAOYSA-N 4-methylselanylbutanenitrile Chemical compound C[Se]CCCC#N QXCFWBGPRMYUTM-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- KOYSIBNLFAIEQF-UHFFFAOYSA-N C(C1=CC=CC=C1)[Se]CCCC#N Chemical compound C(C1=CC=CC=C1)[Se]CCCC#N KOYSIBNLFAIEQF-UHFFFAOYSA-N 0.000 description 3
- UBSYPXSGULNPKG-UHFFFAOYSA-N C1(=CC=CC=C1)C(CC#N)C[Se]C1=CC=CC=C1 Chemical compound C1(=CC=CC=C1)C(CC#N)C[Se]C1=CC=CC=C1 UBSYPXSGULNPKG-UHFFFAOYSA-N 0.000 description 3
- OQPOFWBZBMVVOJ-UHFFFAOYSA-N C1(=CC=CC=C1)[Se]COCC#N Chemical compound C1(=CC=CC=C1)[Se]COCC#N OQPOFWBZBMVVOJ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 3
- 238000004293 19F NMR spectroscopy Methods 0.000 description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000007146 photocatalysis Methods 0.000 description 2
- 230000001699 photocatalysis Effects 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- YQNVPNRHJFZONU-UHFFFAOYSA-N 2,3-dimethylbutan-2-amine Chemical compound CC(C)C(C)(C)N YQNVPNRHJFZONU-UHFFFAOYSA-N 0.000 description 1
- NPAXPTHCUCUHPT-UHFFFAOYSA-N 3,4,7,8-tetramethyl-1,10-phenanthroline Chemical compound CC1=CN=C2C3=NC=C(C)C(C)=C3C=CC2=C1C NPAXPTHCUCUHPT-UHFFFAOYSA-N 0.000 description 1
- BVQSFCUGCAZOJQ-UHFFFAOYSA-N 3-phenylcyclobutan-1-one Chemical compound C1C(=O)CC1C1=CC=CC=C1 BVQSFCUGCAZOJQ-UHFFFAOYSA-N 0.000 description 1
- ZPGVCQYKXIQWTP-UHFFFAOYSA-N 4,7-dimethoxy-1,10-phenanthroline Chemical compound C1=CC2=C(OC)C=CN=C2C2=C1C(OC)=CC=N2 ZPGVCQYKXIQWTP-UHFFFAOYSA-N 0.000 description 1
- DHDHJYNTEFLIHY-UHFFFAOYSA-N 4,7-diphenyl-1,10-phenanthroline Chemical compound C1=CC=CC=C1C1=CC=NC2=C1C=CC1=C(C=3C=CC=CC=3)C=CN=C21 DHDHJYNTEFLIHY-UHFFFAOYSA-N 0.000 description 1
- IBRLCRDTRAPYSF-UHFFFAOYSA-N 4-methyl-1-phenylpent-4-en-1-one Chemical compound CC(=C)CCC(=O)C1=CC=CC=C1 IBRLCRDTRAPYSF-UHFFFAOYSA-N 0.000 description 1
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical compound N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 description 1
- OEUUZWSAIXLWCT-UHFFFAOYSA-N C(#N)CC(C(=O)OCC)C[Se]C1=CC=CC=C1 Chemical compound C(#N)CC(C(=O)OCC)C[Se]C1=CC=CC=C1 OEUUZWSAIXLWCT-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical class [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- 229910001370 Se alloy Inorganic materials 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 150000001336 alkenes Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 230000003712 anti-aging effect Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical compound CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 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
- 201000011510 cancer Diseases 0.000 description 1
- 239000007809 chemical reaction catalyst Substances 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- PGWFQHBXMJMAPN-UHFFFAOYSA-N ctk4b5078 Chemical compound [Cd].OS(=O)(=O)[Se]S(O)(=O)=O PGWFQHBXMJMAPN-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 235000013402 health food Nutrition 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 108091008695 photoreceptors Proteins 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 150000003958 selenols Chemical class 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/20—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C391/00—Compounds containing selenium
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C391/00—Compounds containing selenium
- C07C391/02—Compounds containing selenium having selenium atoms bound to carbon atoms of six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Catalysts (AREA)
- Indole Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
本发明属于合成药物化学技术领域,具体涉及一种有机硒化合物的合成方法。本发明在温和的条件下,以γ,δ‑不饱和肟酯与环酮肟酯(包括γ,δ‑不饱和肟酯衍生物与环酮肟酯衍生物)为原料,以二硒化物为硒化试剂,以廉价过渡金属镍或铁为催化剂,以实现γ,δ‑不饱和肟酯的氨基硒化与环酮肟酯的氰烷基硒化,从而制备出一系列有机硒吡咯啉衍生物与有机硒烷基腈衍生物。本发明不仅产物的收率高,反应条件温和,原料普遍适用性好,而且催化剂廉价易得,扩大量反应仍能表现出较好的重现性。因此,本发明为今后包含此结构的其他高价值化合物的工业化生产提供了一种有效的方案。
Description
技术领域
本发明属于合成药物化学技术领域,涉及一种有机硒化合物的合成方法,具体涉及一种有机硒吡咯啉衍生物与有机硒烷基腈衍生物的合成方法。
背景技术
硒元素作为人体内必需的微量元素之一,在身体的日常代谢中起到抗氧化以及提高身体免疫力的作用,且不会在身体里堆积,因此科学补硒成了人们拥有健康、美好生活的手段。同时在生物医药领域硒元素也被证明是抗癌、抗肿瘤、抗炎的有力帮手。除了在医药行业里被广泛使用以外,硒也被其他行业广泛使用。如硒合金在电子行业可用作感光器、光电池,硫硒化镉在化工颜料行业可用作催化剂、抗氧化剂,有机硒化合物在化妆品行业可用作抗衰老剂和抗氧化剂,天然有机硒化合物在保健食品业可用作食品添加剂。目前关于有机硒的化学合成方法不多,有机硒化合物的种类较少。因此开发通用且实用的新方法来构建C-Se键,拓展有机硒化合物的种类是非常重要的一个步骤。
通常人们对C-Se键的构建通过卤化物或硼酸与硒醇或二硒化物的交叉偶联。此类方法合成的脂肪族硒化合物易挥发、不稳定、且后处理困难。因此在工业应用上受到了一定限制。近年用过渡金属催化的肟酯末端烯烃1,2氨基芳基化的反应与环酮肟酯类衍生物的开环官能化受到了大家的关注和研究。这种方式条件温和,底物普适性强,转化率高,绿色安全,但是利用该路线合成有机硒类化合物的方法存在技术空白的问题。另外,由于有机硒吡咯啉衍生物与有机硒烷基腈衍生物的合成目前只能利用光催化来实现,且光催化的工业化目前存在技术壁垒,而传统的过渡金属催化的工业化路线更加成熟。因此利用过渡金属催化合成有机硒类化合物的方法具有实际的应用价值。
发明内容
有鉴于此,本发明的目的是针对现有技术中存在的问题,提供一种有机硒化合物的合成方法。
本发明具体公开了一种有机硒吡咯啉衍生物与有机硒烷基腈衍生物的合成方法,通过以廉价易得的过渡金属作为反应的催化剂,用二硒化物作为硒化试剂,与γ,δ-不饱和肟酯和环酮肟酯进行硒化反应得到其对应的有机硒产物,不仅官能团兼容范围较广,且该方法中催化剂廉价易得,反应条件温和,收率高,重现性好。
为了实现上述目的,本发明采用如下技术方案:
一种有机硒化合物的合成方法,所述方法具体包括如下步骤:
(1)向25毫升的史莱克管中加入催化剂、配体和有机溶剂,搅拌得反应溶剂,备用;
(2)待步骤(1)反应溶剂冷却至室温后,继续向25毫升的史莱克管中添加肟酯、二硒化物和碱反应;并于反应过程中用TLC进行跟踪以决定具体的反应时间;
(3)待步骤(2)的反应结束后,将溶剂旋干,并用硅胶柱进行纯化得到所述有机硒化合物,即为有机硒吡咯啉衍生物与有机硒烷基腈衍生物。
合成路线为:
其中,R、R1、R2、R3、R4、R5、R6至少选自氢、烷基、杂环、卤素、芳基、取代芳基、酯基中的一种;R3和R4相同或不同。
进一步的,步骤(1)中的搅拌温度为80℃,搅拌时间为30min;步骤(2)中的反应温度为90℃,反应时间为12-24h。
进一步的,所述肟酯在反应溶剂中的摩尔浓度为0.2~1.0mmol/mL,及所述有机溶剂为1,4-二氧六环、甲苯、四氢呋喃、二氯甲烷、乙腈、环己烷、N,N-二甲基甲酰胺、二甲基亚砜、乙酸乙酯或N-甲基吡咯烷酮,且所述有机溶剂的用量为2-8mL。
进一步的,所述催化剂为双-(1,5-环辛二烯镍)或氯化亚铁,及所述催化剂的用量为肟酯用量的5mol%~30mol%;所述配体为含氮双齿配体,具体包括2,2'-联吡啶、4,4'-二叔丁基-2,2'-联吡啶、4,4'-二甲氧基-2,2'-联吡啶、1,10-菲罗啉、3,4,7,8-四甲基-1,10-菲罗啉、4,7-二苯基-1,10-菲罗啉或4,7-二甲氧基-1,10-菲咯啉,且所述配体用量为肟酯用量的5mol%-30mol%。
进一步的,所述碱为有机或无机碱,包括三乙胺、二异丙基乙基胺、四甲基乙基胺、叔丁醇钾、碳酸铯、碳酸钾、碳酸钠或氢氧化钠,碱的用量为肟酯用量的1e-15e;所述硒化试剂为芳基二硒醚或烷基二硒醚,及肟酯与硒化试剂的摩尔比为2:1~1:2。
进一步的,所述步骤3)中的处理及纯化方法:先将反应后的溶剂旋干,进一步用柱层析法纯化分离;
其中,柱层析可以选择200~300目的硅胶作为固定相,展开剂为石油醚和乙酸乙酯的混合溶液。
与现有技术相比,本发明优点在于:产率高,反应条件相对温和,催化剂廉价易得,环保安全,重现性好,更加具有工业化应用潜力,该技术填补了多种有机硒吡咯啉衍生物与有机硒烷基腈衍生物合成路线的技术空白。
附图说明
为了更清楚地说明本发明实施例或现有技术中的技术方案,下面将对实施例或现有技术描述中所需要使用的附图作简单地介绍,显而易见地,下面描述中的附图仅仅是本发明的实施例,对于本领域普通技术人员来讲,在不付出创造性劳动的前提下,还可以根据提供的附图获得其他的附图
图1为实施例3的谱图。
图2为实施例5的谱图。
图3为实施例13的谱图。
图4为实施例25的谱图。
图5为实施例26的谱图。
具体实施方式
下面将对本发明实施例中的技术方案进行清楚、完整地描述,显然,所描述的实施例仅是本发明一部分实施例,而不是全部的实施例。基于本发明中的实施例,本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例,都属于本发明保护的范围。
为更好地理解本发明,下面通过以下实施例对本发明作进一步具体的阐述,但不可理解为对本发明的限定,对于本领域的技术人员根据上述发明内容所作的一些非本质的改进与调整,也视为落在本发明的保护范围内。
实施例1:5-苯基-2-((苯基硒基)甲基)-3,4-二氢-2H-吡咯的制备
在惰性气体保护下,称取双-(1,5-环辛二烯镍)(11.0mg,20mol%)、1,10-菲罗啉(7.2mg,20mol%)、1,4-二氧六环(6mL)加入史莱克管中,加热至80℃搅拌反应0.5h,冷却至室温后直接用于下一步。在装有催化剂-配体络合物的史莱克管中仍然在惰性气体保护下加入1-苯基戊-4-烯-1-酮O-全氟苯甲酰肟(73.8mg,0.2mmol),二苯基二硒醚(94.2mg,1.5equiv),三乙胺(202.4mg,10equiv)。室温搅拌反应12h。所得反应物用硅胶柱(石油醚/乙酸乙酯)纯化得到5-苯基-2-((苯基硒基)甲基)-3,4-二氢-2H-吡咯(56.9mg)产率90%。
5-苯基-2-((苯基硒基)甲基)-3,4-二氢-2H-吡咯
1H NMR(400MHz,Chloroform-d)δ7.84–7.75(m,2H),7.60–7.52(m,2H),7.41(dd,J=9.1,6.9Hz,3H),7.24(d,J=6.8Hz,3H),4.58–4.47(m,1H),3.47(dd,J=12.0,4.7Hz,1H),3.09(dd,J=12.1,7.9Hz,2H),2.99–2.85(m,1H),2.29(dt,J=8.0,2.5Hz,1H),1.88–1.74(m,1H);13C NMR(101MHz,Chloroform-d)δ173.52,134.41,132.70,130.70,129.13,128.52,127.91,126.86,125.90,72.96,35.48,34.47,28.70.
实施例2:5-苯基-2-((苯基硒基)甲基)-3,4-二氢-2H-吡咯的制备
在惰性气体保护下,称取氯化亚铁(5.1mg,20mol%)、1,10-菲罗啉(7.2mg,20mol%)、1,4-二氧六环(6mL)加入史莱克管中,加热至80℃搅拌反应0.5h,冷却至室温后直接用于下一步。在装有催化剂-配体络合物的史莱克管中仍然在惰性气体保护下加入1-苯基戊-4-烯-1-酮O-全氟苯甲酰肟(73.8mg,0.2mmol),二苯基二硒醚(94.2mg,1.5equiv),三乙胺(202.4mg,10equiv)。室温搅拌反应24h。所得反应物用硅胶柱(石油醚/乙酸乙酯)纯化得到5-苯基-2-((苯基硒基)甲基)-3,4-二氢-2H-吡咯(50.4mg)产率80%。
5-苯基-2-((苯基硒基)甲基)-3,4-二氢-2H-吡咯
1H NMR(400MHz,Chloroform-d)δ7.84–7.75(m,2H),7.60–7.52(m,2H),7.41(dd,J=9.1,6.9Hz,3H),7.24(d,J=6.8Hz,3H),4.58–4.47(m,1H),3.47(dd,J=12.0,4.7Hz,1H),3.09(dd,J=12.1,7.9Hz,2H),2.99–2.85(m,1H),2.29(dt,J=8.0,2.5Hz,1H),1.88–1.74(m,1H);13C NMR(101MHz,Chloroform-d)δ173.52,134.41,132.70,130.70,129.13,128.52,127.91,126.86,125.90,72.96,35.48,34.47,28.70.
实施例3:5-(4-氯苯基)-2-((苯基硒基)甲基)-3,4-二氢-2H-吡咯的制备
在惰性气体保护下,称取双-(1,5-环辛二烯镍)(11.0mg,20mol%)、1,10-菲罗啉(7.2mg,20mol%)、1,4-二氧六环(6mL)加入史莱克管中,加热至80℃搅拌反应0.5h,冷却至室温后直接用于下一步。在装有催化剂-配体络合物的史莱克管中仍然在惰性气体保护下加入1-(4-氯苯基)戊-4-烯-1-酮O-全氟苯甲酰肟(80.6mg,0.2mmol),二苯基二硒醚(94.2mg,1.5equiv),三乙胺(202.4mg,10equiv)。室温搅拌反应12h。所得反应物用硅胶柱(石油醚/乙酸乙酯)纯化得到5-(4-氯苯基)-2-((苯基硒基)甲基)-3,4-二氢-2H-吡咯(46.1mg)产率66%。
5-(4-氯苯基)-2-((苯基硒基)甲基)-3,4-二氢-2H-吡咯
1H NMR(400MHz,Chloroform-d)δ7.72(d,J=8.6Hz,2H),7.54(dd,J=7.6,1.9Hz,2H),7.36(d,J=8.6Hz,2H),7.25–7.18(m,3H),4.52(s,1H),3.43(dd,J=12.1,4.8Hz,1H),3.17–2.98(m,2H),2.96–2.82(m,1H),2.36–2.22(m,1H),1.88–1.74(m,1H);13C NMR(151MHz,Chloroform-d)δ172.38,136.76,132.91,132.73,130.63,129.24,129.17,128.77,126.93,73.12,35.51,34.47,28.79;HRMS(ESI):m/z calcd for C17H16ClNSe[M+H]+350.0214,found 350.0214.
实施例4:5-(4-甲氧基苯基)-2-((苯基己烯基)甲基)-3,4-二氢-2H-吡咯的制备
在惰性气体保护下,称取双-(1,5-环辛二烯镍)(11.0mg,20mol%)、1,10-菲罗啉(7.2mg,20mol%)、1,4-二氧六环(6mL)加入史莱克管中,加热至80℃搅拌反应0.5h,冷却至室温后直接用于下一步。在装有催化剂-配体络合物的史莱克管中仍然在惰性气体保护下加入1-(4-甲氧基苯基)戊-4-烯-1-酮O-全氟苯甲酰肟(79.8mg,0.2mmol),二苯基二硒醚(94.2mg,1.5equiv),三乙胺(202.4mg,10equiv)。室温搅拌反应12h。所得反应物用硅胶柱(石油醚/乙酸乙酯)纯化得到5-(4-甲氧基苯基)-2-((苯基己烯基)甲基)-3,4-二氢-2H-吡咯(56.0mg)产率81%。
5-(4-甲氧基苯基)-2-((苯基己烯基)甲基)-3,4-二氢-2H-吡咯
1H NMR(400MHz,Chloroform-d)δ7.75(d,J=8.8Hz,2H),7.55(d,J=7.9Hz,2H),7.23(d,J=7.1Hz,3H),6.90(d,J=8.8Hz,2H),4.54–4.43(m,1H),3.84(s,3H),3.46(dd,J=12.0,4.7Hz,1H),3.13–2.98(m,2H),2.95–2.81(m,1H),2.32–2.22(m,1H),1.77(d,J=23.5Hz,1H);13C NMR(151MHz,Chloroform-d)δ172.85,161.69,132.67,130.71,129.61,129.12,127.14,126.83,113.83,72.69,55.47,35.36,34.57,28.76;HRMS(ESI):m/z calcdfor C18H19NOSe[M+H]+346.0710,found 346.0711.
实施例5:5-(3-氯苯基)-2-(苯基己烯基)甲基)-3,4-二氢-2H-吡咯的制备
在惰性气体保护下,称取双-(1,5-环辛二烯镍)(11.0mg,20mol%)、1,10-菲罗啉(7.2mg,20mol%)、1,4-二氧六环(6mL)加入史莱克管中,加热至80℃搅拌反应0.5h,冷却至室温后直接用于下一步。在装有催化剂-配体络合物的史莱克管中仍然在惰性气体保护下加入1-(3-氯苯基)戊-4-烯-1-酮O-全氟苯甲酰肟(80.6mg,0.2mmol),二苯基二硒醚(94.2mg,1.5equiv),三乙胺(202.4mg,10equiv)。室温搅拌反应12h。所得反应物用硅胶柱(石油醚/乙酸乙酯)纯化得到5-(3-氯苯基)-2-(苯基己烯基)甲基)-3,4-二氢-2H-吡咯(54.4mg)产率78%。
5-(3-氯苯基)-2-(苯基己烯基)甲基)-3,4-二氢-2H-吡咯
1H NMR(400MHz,Chloroform-d)δ7.79(s,1H),7.63(d,J=7.7Hz,1H),7.55(d,J=7.8Hz,2H),7.42–7.18(m,5H),4.53(t,J=6.8Hz,1H),3.43(dd,J=12.2,4.9Hz,1H),3.18–2.96(m,2H),2.93–2.80(m,1H),2.34–2.21(m,1H),1.88–1.76(m,1H);13C NMR(101MHz,Chloroform-d)δ172.27,136.19,134.66,132.75,130.64,130.59,129.78,129.16,127.97,126.96,126.05,73.15,35.54,34.43,28.71;HRMS(ESI):m/z calcd for C17H16ClNSe[M+H]+350.0214,found 350.0224.
实施例6:5-(3-甲氧基苯基)-2-((苯基硒基)甲基)-3,4-二氢-2H-吡咯的制备
在惰性气体保护下,称取双-(1,5-环辛二烯镍)(11.0mg,20mol%)、1,10-菲罗啉(7.2mg,20mol%)、1,4-二氧六环(6mL)加入史莱克管中,加热至80℃搅拌反应0.5h,冷却至室温后直接用于下一步。在装有催化剂-配体络合物的史莱克管中仍然在惰性气体保护下加入1-(3-甲氧基苯基)戊-4-烯-1-酮O-全氟苯甲酰肟(79.8mg,0.2mmol),二苯基二硒醚(94.2mg,1.5equiv),三乙胺(202.4mg,10equiv)。室温搅拌反应12h。所得反应物用硅胶柱(石油醚/乙酸乙酯)纯化得到5-(3-甲氧基苯基)-2-((苯基硒基)甲基)-3,4-二氢-2H-吡咯(55.2mg)产率80%。
5-(3-甲氧基苯基)-2-((苯基硒基)甲基)-3,4-二氢-2H-吡咯
1HNMR(400MHz,Chloroform-d)δ7.59–7.50(m,2H),7.40(s,1H),7.36–7.27(m,2H),7.23(d,J=6.6Hz,3H),6.98(d,J=7.8Hz,1H),4.58–4.47(m,1H),3.84(s,3H),3.47(dd,J=12.1,4.6Hz,1H),3.06(t,J=12.3Hz,2H),2.98–2.84(m,1H),2.35–2.22(m,1H),1.83(d,J=16.9Hz,1H);13C NMR(101MHz,Chloroform-d)δ173.48,159.75,135.81,132.75,130.69,129.51,129.14,126.89,120.71,117.24,112.25,72.97,55.53,35.61,34.49,28.72;HRMS(ESI):m/z calcd for C18H19NOSe[M+H]+346.0710,found 346.0713.
实施例7:2-((苯基硒基)甲基)-5-(噻吩-2-基)-3,4-二氢-2H-吡咯的制备
在惰性气体保护下,称取双-(1,5-环辛二烯镍)(11.0mg,20mol%)、1,10-菲罗啉(7.2mg,20mol%)、1,4-二氧六环(6mL)加入史莱克管中,加热至80℃搅拌反应0.5h,冷却至室温后直接用于下一步。在装有催化剂-配体络合物的史莱克管中仍然在惰性气体保护下加入1-(噻吩-2-基)戊-4-烯-1-酮O-全氟苯甲酰肟(75.0mg,0.2mmol),二苯基二硒醚(94.2mg,1.5equiv),三乙胺(202.4mg,10equiv)。室温搅拌反应12h。所得反应物用硅胶柱(石油醚/乙酸乙酯)纯化得到2-((苯基硒基)甲基)-5-(噻吩-2-基)-3,4-二氢-2H-吡咯(43.7mg)产率54%。
2-((苯基硒基)甲基)-5-(噻吩-2-基)-3,4-二氢-2H-吡咯
1H NMR(400MHz,Chloroform-d)δ7.53–7.46(m,2H),7.11(dd,J=5.1,3.7Hz,1H),5.83(td,J=16.9,6.7Hz,1H),5.16–4.98(m,2H),3.01–2.92(m,2H),2.48–2.37(m,2H);13CNMR(151MHz,Chloroform-d)δ163.27,156.35,146.50(d,J=11.3Hz),144.65(d,J=44.2Hz),142.81,138.74(d,J=12.9Hz),137.08(d,J=28.2Hz),136.21,136.14,130.43,130.17,127.70,116.40,107.01(d,J=33.8Hz),31.40,28.98;HRMS(ESI):m/z calcd forC15H15NSSe[M+H]+322.0169,found 322.0172.
实施例8:5-(呋喃-2-基)-2-((苯基硒基)甲基)-3,4-二氢-2H-吡咯的制备
在惰性气体保护下,称取双-(1,5-环辛二烯镍)(11.0mg,20mol%)、1,10-菲罗啉(7.2mg,20mol%)、1,4-二氧六环(6mL)加入史莱克管中,加热至80℃搅拌反应0.5h,冷却至室温后直接用于下一步。在装有催化剂-配体络合物的史莱克管中仍然在惰性气体保护下加入1-(呋喃-2-基)戊-4-烯-1-酮O-全氟苯甲酰肟(71.8mg,0.2mmol),二苯基二硒醚(94.2mg,1.5equiv),三乙胺(202.4mg,10equiv)。室温搅拌反应12h。所得反应物用硅胶柱(石油醚/乙酸乙酯)纯化得到5-(呋喃-2-基)-2-((苯基硒基)甲基)-3,4-二氢-2H-吡咯(36.6mg)产率44%。
5-(呋喃-2-基)-2-((苯基硒基)甲基)-3,4-二氢-2H-吡咯
1H NMR(600MHz,Chloroform-d)δ7.50–7.46(m,3H),7.17(dd,J=9.5,7.0Hz,3H),6.74(d,J=3.4Hz,1H),6.41(dd,J=3.5,1.7Hz,1H),4.45–4.37(m,1H),3.47(dd,J=12.2,4.3Hz,1H),2.94(dd,J=12.1,8.7Hz,2H),2.76(dt,J=19.0,9.7Hz,1H),2.25–2.17(m,1H),1.67(d,J=7.2Hz,1H);13C NMR(151MHz,Chloroform-d)δ164.10,149.87,144.86,132.57,130.45,129.17,126.89,113.65,111.71,73.10,35.30,34.01,28.48;HRMS(ESI):m/z calcd for C15H15NOSe[M+H]+306.0397,found 306.0399.
实施例9:5-苯基-2-(1-(苯基硒基)乙基)-3,4-二氢-2H-吡咯的制备
在惰性气体保护下,称取双-(1,5-环辛二烯镍)(11.0mg,20mol%)、1,10-菲罗啉(7.2mg,20mol%)、1,4-二氧六环(6mL)加入史莱克管中,加热至80℃搅拌反应0.5h,冷却至室温后直接用于下一步。在装有催化剂-配体络合物的史莱克管中仍然在惰性气体保护下加入1-苯基十六烷-4-烯-1-酮O-全氟苯甲酰肟(76.6mg,0.2mmol),二苯基二硒醚(94.2mg,1.5equiv),三乙胺(202.4mg,10equiv)。室温搅拌反应12h。所得反应物用硅胶柱(石油醚/乙酸乙酯)纯化得到5-苯基-2-(1-(苯基硒基)乙基)-3,4-二氢-2H-吡咯(34.1mg)产率52%。
5-苯基-2-(1-(苯基硒基)乙基)-3,4-二氢-2H-吡咯
1H NMR(400MHz,Chloroform-d)δ7.83–7.77(m,2H),7.60–7.56(m,2H),7.38(d,J=7.7Hz,3H),7.23(dd,J=4.1,2.3Hz,3H),4.50–4.40(m,1H),3.85–3.74(m,1H),3.11–2.83(m,2H),2.22–2.09(m,1H),1.95(d,J=10.3Hz,1H),1.38(d,J=7.0Hz,3H);13C NMR(101MHz,Chloroform-d)δ173.55,134.57,134.51,130.66,129.88,129.10,128.54,127.91,127.39,77.30,44.39,35.76,25.17,17.50;HRMS(ESI):m/z calcd for C18H19NSe[M+H]+330.0761,found 330.0765.
实施例10:5-苯基-2-(2-(苯基硒基)丙-2-基)-3,4-二氢-2H-吡咯的制备
在惰性气体保护下,称取双-(1,5-环辛二烯镍)(11.0mg,20mol%)、1,10-菲罗啉(7.2mg,20mol%)、1,4-二氧六环(6mL)加入史莱克管中,加热至80℃搅拌反应0.5h,冷却至室温后直接用于下一步。在装有催化剂-配体络合物的史莱克管中仍然在惰性气体保护下加入5-甲基-1-苯基十六烷-4-烯-1-酮O-全氟苯甲酰肟(76.4mg,0.2mmol),二苯基二硒醚(94.2mg,1.5equiv),三乙胺(202.4mg,10equiv)。室温搅拌反应12h。所得反应物用硅胶柱(石油醚/乙酸乙酯)纯化得到5-苯基-2-(2-(苯基硒基)丙-2-基)-3,4-二氢-2H-吡咯(48.0mg)产率70%。
5-苯基-2-(2-(苯基硒基)丙-2-基)-3,4-二氢-2H-吡咯
1H NMR(400MHz,Chloroform-d)δ7.69(dd,J=7.7,1.9Hz,2H),7.56–7.48(m,2H),7.35–7.16(m,4H),7.15–7.02(m,2H),4.18–4.08(m,1H),2.95–2.71(m,2H),2.11–1.86(m,2H),1.36(s,3H),1.26(s,3H);13C NMR(101MHz,Chloroform-d)δ173.13,138.61,134.70,130.50,128.74–128.35(m),127.85(d,J=13.6Hz),82.52,51.92,35.59,28.31,26.37,25.55.
实施例11:2-甲基-5-苯基-2-((苯基硒基)甲基)-3,4-二氢-2H-吡咯的制备
在惰性气体保护下,称取双-(1,5-环辛二烯镍)(11.0mg,20mol%)、1,10-菲罗啉(7.2mg,20mol%)、1,4-二氧六环(6mL)加入史莱克管中,加热至80℃搅拌反应0.5h,冷却至室温后直接用于下一步。在装有催化剂-配体络合物的史莱克管中仍然在惰性气体保护下加入4-甲基-1-苯基戊-4-烯-1-酮O-全氟苯甲酰肟(76.6mg,0.2mmol),二苯基二硒醚(94.2mg,1.5equiv),三乙胺(202.4mg,10equiv)。室温搅拌反应12h。所得反应物用硅胶柱(石油醚/乙酸乙酯)纯化得到2-甲基-5-苯基-2-((苯基硒基)甲基)-3,4-二氢-2H-吡咯(34.9mg)产率53%。
2-甲基-5-苯基-2-((苯基硒基)甲基)-3,4-二氢-2H-吡咯
1H NMR(400MHz,Chloroform-d)δ7.85–7.77(m,2H),7.55(dd,J=7.6,2.0Hz,2H),7.42(dd,J=9.3,7.1Hz,3H),7.23(q,J=5.1Hz,3H),3.35(d,J=10.4Hz,2H),3.09(t,J=8.0Hz,2H),2.16(dt,J=12.9,8.1Hz,1H),1.97–1.84(m,1H),1.49(s,3H);13C NMR(101MHz,Chloroform-d)δ171.38,134.54,132.42,131.76,130.54,129.04,128.44,127.93,126.62,76.92,41.55,35.97,34.08,27.83;HRMS(ESI):m/z calcd for C18H19NSe[M+H]+330.0761,found 330.0767.
实施例12:2-((苯基硒基)甲基)-3,3a,4,5-四氢-2H-苯并(g)吲哚的制备
在惰性气体保护下,称取双-(1,5-环辛二烯镍)(11.0mg,20mol%)、1,10-菲罗啉(7.2mg,20mol%)、1,4-二氧六环(6mL)加入史莱克管中,加热至80℃搅拌反应0.5h,冷却至室温后直接用于下一步。在装有催化剂-配体络合物的史莱克管中仍然在惰性气体保护下加入2-烯丙基-3,4-二氢萘-1(2H)-酮-O-全氟苯甲酰肟(79.0mg,0.2mmol),二苯基二硒醚(94.2mg,1.5equiv),三乙胺(202.4mg,10equiv)。室温搅拌反应12h。所得反应物用硅胶柱(石油醚/乙酸乙酯)纯化得到2-((苯基硒基)甲基)-3,3a,4,5-四氢-2H-苯并(g)吲哚(34.8mg)产率51%。
2-((苯基硒基)甲基)-3,3a,4,5-四氢-2H-苯并(g)吲哚
(obtained in a 2.2:1ratio of diastereomers,data are given for themixture);1H NMR(400MHz,Chloroform-d)δ8.08(dd,J=7.7,1.4Hz,2H(major isomer)),8.03(dd,J=7.9,1.4Hz,1H(minor isomer)),7.65–7.49(m,6H(major isomer)),7.34(td,J=7.5,1.6Hz,3H(minor isomer)),7.30–7.03(m,8H(major isomer)+4H(minorisomer)),4.64(td,J=8.6,4.2Hz,1H(minor isomer)),4.28–4.10(m,2H(majorisomer)),3.63(dd,J=11.9,4.9Hz,2H(major isomer)),3.29(dd,J=12.2,4.5Hz,1H(minor isomer)),3.19–2.76(m,8H(major isomer)+4H(minor isomer)),2.54(ddd,J=12.3,7.9,6.2Hz,2H(minor isomer)),2.33–2.19(m,4H(major isomer)),1.79(dt,J=13.1,9.2Hz,1H(minor isomer)),1.69(td,J=12.9,4.8Hz,2H(major isomer)),1.65–1.53(m,1H(minor isomer)),1.40–1.23(m,2H(major isomer));13C NMR(101MHz,Chloroform-d)δ174.59,174.12,141.21,132.60,132.56,131.56,130.98,130.95,130.66,130.61,130.04,129.96,129.28,129.13,129.10,128.95,128.90,126.85,126.79,126.54,126.49,126.20,126.06,71.12,71.01,47.85,45.99,37.75,34.90,34.63,32.66,30.14,30.09,30.00,29.73;HRMS(ESI):m/z calcd for C19H19NSe[M+H]+342.0761,found342.0768.
实施例13:2-(((4-甲氧基苯基)硒基)甲基)-5-苯基-3,4-二氢-2H-吡咯的制备
在惰性气体保护下,称取氯化亚铁(5.1mg,20mol%)、1,10-菲罗啉(7.2mg,20mol%)、1,4-二氧六环(6mL)加入史莱克管中,加热至80℃搅拌反应0.5h,冷却至室温后直接用于下一步。在装有催化剂-配体络合物的史莱克管中仍然在惰性气体保护下加入1-苯基戊-4-烯-1-酮O-全氟苯甲酰肟(73.8mg,0.2mmol),二(4-甲氧基苯基)二硒醚(112.2mg,1.5equiv),三乙胺(202.4mg,10equiv)。室温搅拌反应24h。所得反应物用硅胶柱(石油醚/乙酸乙酯)纯化得到2-(((4-甲氧基苯基)硒基)甲基)-5-苯基-3,4-二氢-2H-吡咯(38.2mg)产率55%。
2-(((4-甲氧基苯基)硒基)甲基)-5-苯基-3,4-二氢-2H-吡咯
1H NMR(400MHz,Chloroform-d)δ7.88–7.76(m,2H),7.52(d,J=8.8Hz,2H),7.41(t,J=7.7Hz,4H),6.79(d,J=8.7Hz,2H),4.52–4.40(m,1H),3.78(s,3H),3.39(dd,J=12.1,4.6Hz,1H),3.14–3.02(m,1H),3.02–2.84(m,2H),2.33–2.21(m,1H),1.85–1.74(m,1H);13C NMR(101MHz,Chloroform-d)δ173.31,159.31,135.64,134.49,130.63,128.49,127.87,120.30,114.84,73.13,55.39,35.52,35.41,28.65;HRMS(ESI):m/z calcd forC18H19NOSe[M+H]+346.0710,found 346.0718.
实施例14:2-(((4-氟苯基)硒基)甲基)-5-苯基-3,4-二氢-2H-吡咯的制备
在惰性气体保护下,称取氯化亚铁(5.1mg,20mol%)、1,10-菲罗啉(7.2mg,20mol%)、1,4-二氧六环(6mL)加入史莱克管中,加热至80℃搅拌反应0.5h,冷却至室温后直接用于下一步。在装有催化剂-配体络合物的史莱克管中仍然在惰性气体保护下加入1-苯基戊-4-烯-1-酮O-全氟苯甲酰肟(73.8mg,0.2mmol),二(4-氟苯基)二硒醚(105.0mg,1.5equiv),三乙胺(202.4mg,10equiv)。室温搅拌反应24h。所得反应物用硅胶柱(石油醚/乙酸乙酯)纯化得到2-(((4-氟苯基)硒基)甲基)-5-苯基-3,4-二氢-2H-吡咯(38.9mg)产率58%。
2-(((4-氟苯基)硒基)甲基)-5-苯基-3,4-二氢-2H-吡咯
1H NMR(400MHz,Chloroform-d)δ7.84–7.73(m,2H),7.54(dd,J=8.6,5.5Hz,2H),7.46–7.36(m,3H),6.94(t,J=8.8Hz,2H),4.55–4.43(m,1H),3.40(dd,J=12.1,4.8Hz,1H),3.16–3.00(m,2H),2.99–2.86(m,1H),2.35–2.18(m,1H),1.86–1.72(m,1H);13C NMR(101MHz,Chloroform-d)δ173.49,162.40(d,J=246.4Hz),135.36(d,J=7.7Hz),130.74,128.54,127.89,124.96(d,J=3.5Hz),116.27(d,J=21.5Hz),73.00,35.49(d,J=1.6Hz),28.69;19F NMR(376MHz,Chloroform-d)δ-115.10;HRMS(ESI):m/z calcd for C17H16FNSe[M+H]+334.0510,found 334.0515.
实施例15:2-((苄基硒基)甲基)-5-苯基-3,4-二氢-2H-吡咯的制备
在惰性气体保护下,称取氯化亚铁(5.1mg,20mol%)、1,10-菲罗啉(7.2mg,20mol%)、1,4-二氧六环(6mL)加入史莱克管中,加热至80℃搅拌反应0.5h,冷却至室温后直接用于下一步。在装有催化剂-配体络合物的史莱克管中仍然在惰性气体保护下加入1-苯基戊-4-烯-1-酮O-全氟苯甲酰肟(73.8mg,0.2mmol),二苄基二硒醚(102.6mg,1.5equiv),三乙胺(202.4mg,10equiv)。室温搅拌反应24h。所得反应物用硅胶柱(石油醚/乙酸乙酯)纯化得到2-((苄基硒基)甲基)-5-苯基-3,4-二氢-2H-吡咯(48.0mg)产率73%。
2-((苄基硒基)甲基)-5-苯基-3,4-二氢-2H-吡咯
1H NMR(400MHz,Chloroform-d)δ7.85(dd,J=7.8,1.9Hz,2H),7.42(d,J=2.1Hz,3H),7.29(dd,J=9.2,6.7Hz,4H),7.22–7.16(m,1H),4.57–4.46(m,1H),3.87(s,2H),3.12–3.01(m,1H),2.98–2.88(m,2H),2.83(dd,J=12.3,6.9Hz,1H),2.29–2.16(m,1H),1.77–1.68(m,1H);13C NMR(101MHz,Chloroform-d)δ173.22,139.76,134.53,130.66,129.15,129.06,128.59,127.89,126.75,73.54,35.53,30.73,28.80,28.12;HRMS(ESI):m/z calcdfor C18H19NSe[M+H]+330.0761,found 330.0765.
实施例16:2-((甲基硒基)甲基)-5-苯基-3,4-二氢-2H-吡咯的制备
在惰性气体保护下,称取氯化亚铁(5.1mg,20mol%)、1,10-菲罗啉(7.2mg,20mol%)、1,4-二氧六环(6mL)加入史莱克管中,加热至80℃搅拌反应0.5h,冷却至室温后直接用于下一步。在装有催化剂-配体络合物的史莱克管中仍然在惰性气体保护下加入1-苯基戊-4-烯-1-酮O-全氟苯甲酰肟(73.8mg,0.2mmol),二甲基二硒醚(57.0mg,1.5equiv),三乙胺(202.4mg,10equiv)。室温搅拌反应24h。所得反应物用硅胶柱(石油醚/乙酸乙酯)纯化得到2-((甲基硒基)甲基)-5-苯基-3,4-二氢-2H-吡咯(27.1mg)产率54%。
2-((甲基硒基)甲基)-5-苯基-3,4-二氢-2H-吡咯
1H NMR(600MHz,Chloroform-d)δ7.84(d,J=6.5Hz,2H),7.49–7.37(m,3H),4.57–4.49(m,1H),3.13–3.05(m,1H),3.02(dd,J=12.4,4.8Hz,1H),2.97–2.89(m,1H),2.80(dd,J=12.4,7.4Hz,1H),2.33–2.22(m,1H),2.06(s,3H),1.84–1.75(m,1H);13C NMR(151MHz,Chloroform-d)δ173.26,134.46,130.68,128.56,127.88,73.41,35.45,32.25,28.66,5.41;HRMS(ESI):m/z calcd for C12H15NSe[M+H]+254.0448,found 254.0450.
实施例17:4-(苯基硒基)丁腈的制备
在惰性气体保护下,称取双-(1,5-环辛二烯镍)(11.0mg,20mol%)、1,10-菲罗啉(7.2mg,20mol%)、1,4-二氧六环(6mL)加入史莱克管中,加热至80℃搅拌反应0.5h,冷却至室温后直接用于下一步。在装有催化剂-配体络合物的史莱克管中仍然在惰性气体保护下加入环丁酮O-全氟苯甲酰肟(55.8mg,0.2mmol),二苯基二硒醚(94.2mg,1.5equiv),三乙胺(202.4mg,10equiv)。室温搅拌反应12h。所得反应物用硅胶柱(石油醚/乙酸乙酯)纯化得到4-(苯基硒基)丁腈(46.4mg)产率86%。
4-(苯基硒基)丁腈
1H NMR(400MHz,Chloroform-d)δ7.55–7.46(m,2H),7.34–7.24(m,3H),2.99(t,J=7.0Hz,2H),2.49(t,J=7.0Hz,2H),2.07–1.93(m,2H);13C NMR(101MHz,Chloroform-d)δ133.35,129.43,128.82,127.63,119.16,26.16,25.82,17.13.
实施例18:4-(苯基硒基)丁腈的制备
在惰性气体保护下,称取氯化亚铁(5.1mg,20mol%)、1,10-菲罗啉(7.2mg,20mol%)、1,4-二氧六环(6mL)加入史莱克管中,加热至80℃搅拌反应0.5h,冷却至室温后直接用于下一步。在装有催化剂-配体络合物的史莱克管中仍然在惰性气体保护下加入环丁酮O-全氟苯甲酰肟(55.8mg,0.2mmol),二苯基二硒醚(94.2mg,1.5equiv),三乙胺(202.4mg,10equiv)。室温搅拌反应24h。所得反应物用硅胶柱(石油醚/乙酸乙酯)纯化得到4-(苯基硒基)丁腈(44.1mg)产率98%。
4-(苯基硒基)丁腈
1H NMR(400MHz,Chloroform-d)δ7.55–7.46(m,2H),7.34–7.24(m,3H),2.99(t,J=7.0Hz,2H),2.49(t,J=7.0Hz,2H),2.07–1.93(m,2H);13C NMR(101MHz,Chloroform-d)δ133.35,129.43,128.82,127.63,119.16,26.16,25.82,17.13.
实施例19:3-苯基-4-(苯基硒基)丁腈的制备
在惰性气体保护下,称取双-(1,5-环辛二烯镍)(11.0mg,20mol%)、1,10-菲罗啉(7.2mg,20mol%)、1,4-二氧六环(6mL)加入史莱克管中,加热至80℃搅拌反应0.5h,冷却至室温后直接用于下一步。在装有催化剂-配体络合物的史莱克管中仍然在惰性气体保护下加入3-苯基环丁烷-1-酮O-全氟苯甲酰肟(71.0mg,0.2mmol),二苯基二硒醚(94.2mg,1.5equiv),三乙胺(202.4mg,10equiv)。室温搅拌反应12h。所得反应物用硅胶柱(石油醚/乙酸乙酯)纯化得到3-苯基-4-(苯基硒基)丁腈(45.8mg)产率76%。
3-苯基-4-(苯基硒基)丁腈
1H NMR(400MHz,Chloroform-d)δ7.51–7.42(m,2H),7.39–7.21(m,6H),7.18(d,J=7.9Hz,2H),3.29(dd,J=12.3,6.2Hz,1H),3.26–3.07(m,2H),2.86(dd,J=16.8,5.3Hz,1H),2.75(dd,J=16.8,7.5Hz,1H);13C NMR(101MHz,Chloroform-d)δ140.70,133.23,129.45,129.11,129.09,128.04,127.64,127.15,118.21,42.27,32.71,24.16.
实施例20:3-氰基-2-((苯基硒基)甲基)丙酸乙酯的制备
在惰性气体保护下,称取双-(1,5-环辛二烯镍)(11.0mg,20mol%)、1,10-菲罗啉(7.2mg,20mol%)、1,4-二氧六环(6mL)加入史莱克管中,加热至80℃搅拌反应0.5h,冷却至室温后直接用于下一步。在装有催化剂-配体络合物的史莱克管中仍然在惰性气体保护下加入乙基-3-(((全氟苯甲酰)氧基)亚氨基)环丁烷-1-羧酸酯(70.2mg,0.2mmol),二苯基二硒醚(94.2mg,1.5equiv),三乙胺(202.4mg,10equiv)。室温搅拌反应12h。所得反应物用硅胶柱(石油醚/乙酸乙酯)纯化得到3-氰基-2-((苯基硒基)甲基)丙酸乙酯(29.7mg)产率50%。
3-氰基-2-((苯基硒基)甲基)丙酸乙酯
1H NMR(600MHz,Chloroform-d)δ7.57–7.51(m,2H),7.33–7.26(m,3H),4.11(ddq,J=41.3,10.7,7.1Hz,2H),3.33(dd,J=13.1,5.6Hz,1H),3.13(dd,J=13.2,7.4Hz,1H),2.98–2.91(m,1H),2.80(dd,J=6.5,0.9Hz,2H),1.24(t,J=7.1Hz,3H);13C NMR(151MHz,Chloroform-d)δ171.01,133.78,129.56,128.41,128.08,117.51,61.96,42.22,28.17,19.36,14.19.
实施例21:4-(苯基硒基)戊腈的制备
在惰性气体保护下,称取双-(1,5-环辛二烯镍)(11.0mg,20mol%)、1,10-菲罗啉(7.2mg,20mol%)、1,4-二氧六环(6mL)加入史莱克管中,加热至80℃搅拌反应0.5h,冷却至室温后直接用于下一步。在装有催化剂-配体络合物的史莱克管中仍然在惰性气体保护下加入2-甲基环丁烷-1-酮O-全氟苯甲酰肟(58.6mg,0.2mmol),二苯基二硒醚(94.2mg,1.5equiv),三乙胺(202.4mg,10equiv)。室温搅拌反应12h。所得反应物用硅胶柱(石油醚/乙酸乙酯)纯化得到4-(苯基硒基)戊腈(35.4mg)产率74%。
4-(苯基硒基)戊腈
1H NMR(400MHz,Chloroform-d)δ7.50–7.43(m,2H),7.21(p,J=7.6,7.2Hz,3H),3.21(h,J=6.9Hz,1H),2.45(td,J=7.3,5.1Hz,2H),1.82(t,J=7.2Hz,2H),1.36(d,J=6.9Hz,3H);13C NMR(101MHz,Chloroform-d)δ135.62,129.27,128.24,127.57,119.37,37.92,32.96,21.97,15.94;HRMS(ESI):m/z calcd for C10H11NSe[M+H]+240.0291,found240.0287.
实施例22:2-((苯基硒基)甲氧基)乙腈的制备
在惰性气体保护下,称取双-(1,5-环辛二烯镍)(11.0mg,20mol%)、1,10-菲罗啉(7.2mg,20mol%)、1,4-二氧六环(6mL)加入史莱克管中,加热至80℃搅拌反应0.5h,冷却至室温后直接用于下一步。在装有催化剂-配体络合物的史莱克管中仍然在惰性气体保护下加入3-氧杂环丁酮O-全氟苯甲酰肟(58.6mg,0.2mmol),二苯基二硒醚(94.2mg,1.5equiv),三乙胺(202.4mg,10equiv)。室温搅拌反应12h。所得反应物用硅胶柱(石油醚/乙酸乙酯)纯化得到2-((苯基硒基)甲氧基)乙腈(35.4mg)产率78%。
2-((苯基硒基)甲氧基)乙腈
1HNMR(400MHz,Chloroform-d)δ7.61–7.53(m,2H),7.36–7.27(m,3H),5.35(s,2H),4.45(s,2H);13C NMR(101MHz,Chloroform-d)δ133.1,129.5,129.1,128.0,115.3,71.8,53.3.
实施例23:2-(((苯基硒基)甲基)硫代)乙腈的制备
在惰性气体保护下,称取双-(1,5-环辛二烯镍)(11.0mg,20mol%)、1,10-菲罗啉(7.2mg,20mol%)、1,4-二氧六环(6mL)加入史莱克管中,加热至80℃搅拌反应0.5h,冷却至室温后直接用于下一步。在装有催化剂-配体络合物的史莱克管中仍然在惰性气体保护下加入3-硫杂环丁酮O-全氟苯甲酰肟(59.4mg,0.2mmol),二苯基二硒醚(94.2mg,1.5equiv),三乙胺(202.4mg,10equiv)。室温搅拌反应12h。所得反应物用硅胶柱(石油醚/乙酸乙酯)纯化得到2-(((苯基硒基)甲基)硫代)乙腈(30.1mg)产率62%。
2-(((苯基硒基)甲基)硫代)乙腈
1HNMR(400MHz,Chloroform-d)δ7.62–7.55(m,2H),7.39–7.27(m,3H),4.13(s,2H),3.49(s,2H);13C NMR(101MHz,Chloroform-d)δ134.1,129.5,128.5,128.4,116.7,29.9,17.7;HRMS(ESI):m/z calcd for C9H9NSSe[M+H]+243.9699,found 243.9703.
实施例24:5-(苯基硒基)己腈的制备
在惰性气体保护下,称取双-(1,5-环辛二烯镍)(11.0mg,20mol%)、1,10-菲罗啉(7.2mg,20mol%)、1,4-二氧六环(6mL)加入史莱克管中,加热至80℃搅拌反应0.5h,冷却至室温后直接用于下一步。在装有催化剂-配体络合物的史莱克管中仍然在惰性气体保护下加入2-甲基环戊烷-1-酮O-全氟苯甲酰肟(61.4mg,0.2mmol),二苯基二硒醚(94.2mg,1.5equiv),三乙胺(202.4mg,10equiv)。室温搅拌反应12h。所得反应物用硅胶柱(石油醚/乙酸乙酯)纯化得到5-(苯基硒基)己腈(38.5mg)产率79%。
5-(苯基硒基)己腈
1H NMR(400MHz,Chloroform-d)δ7.59–7.52(m,2H),7.30(t,J=5.3Hz,3H),3.25(h,J=6.7Hz,1H),2.33(t,J=6.9Hz,2H),1.83(p,J=6.5,6.0Hz,2H),1.78–1.69(m,2H),1.43(d,J=6.9Hz,3H);13C NMR(101MHz,Chloroform-d)δ135.3,129.1,128.5,127.8,119.5,38.6,36.4,23.8,22.3,17.0;HRMS(ESI):m/z calcd for C12H15NSSe[M+H]+254.0448,found 254.0446.
实施例25:6-苯基-6-(苯基硒基)己腈的制备
在惰性气体保护下,称取双-(1,5-环辛二烯镍)(11.0mg,20mol%)、1,10-菲罗啉(7.2mg,20mol%)、1,4-二氧六环(6mL)加入史莱克管中,加热至80℃搅拌反应0.5h,冷却至室温后直接用于下一步。在装有催化剂-配体络合物的史莱克管中仍然在惰性气体保护下加入2-苯基环己-1-酮O-全氟苯甲酰肟(76.6mg,0.2mmol),二苯基二硒醚(94.2mg,1.5equiv),三乙胺(202.4mg,10equiv)。室温搅拌反应12h。所得反应物用硅胶柱(石油醚/乙酸乙酯)纯化得到6-苯基-6-(苯基硒基)己腈(50.7mg)产率77%。
6-苯基-6-(苯基硒基)己腈
1H NMR(400MHz,CDCl3)δ7.42–7.35(m,2H),7.27(d,J=3.2Hz,1H),7.26–7.22(m,3H),7.20(dt,J=5.4,2.4Hz,2H),7.16(dd,J=5.3,3.1Hz,2H),4.23–4.17(m,1H),2.29–2.21(m,2H),2.14–1.97(m,2H),1.69–1.56(m,2H),1.53–1.36(m,2H);13C NMR(101MHz,CDCl3)δ141.8,135.5,129.3,128.8,128.4,127.9,127.6,127.1,119.4,47.9,35.2,27.5,25.0,17.0;HRMS(ESI):m/z calcd for C18H19NSe[M+Na]+352.0576,found 352.0587.
实施例26:7-苯基-7-(苯基硒基)庚腈的制备
在惰性气体保护下,称取双-(1,5-环辛二烯镍)(11.0mg,20mol%)、1,10-菲罗啉(7.2mg,20mol%)、1,4-二氧六环(6mL)加入史莱克管中,加热至80℃搅拌反应0.5h,冷却至室温后直接用于下一步。在装有催化剂-配体络合物的史莱克管中仍然在惰性气体保护下加入2-苯基环庚烷-1-酮O-全氟苯甲酰肟(79.4mg,0.2mmol),二苯基二硒醚(94.2mg,1.5equiv),三乙胺(202.4mg,10equiv)。室温搅拌反应12h。所得反应物用硅胶柱(石油醚/乙酸乙酯)纯化得到7-苯基-7-(苯基硒基)庚腈(53.2mg)产率78%。
7-苯基-7-(苯基硒基)庚腈
1H NMR(400MHz,Chloroform-d)δ7.43–7.37(m,2H),7.30–7.16(m,8H),4.23(dd,J=9.0,6.4Hz,1H),2.27(t,J=7.1Hz,2H),2.13–1.99(m,2H),1.62–1.55(m,2H),1.43(dd,J=14.1,6.4Hz,2H),1.37–1.27(m,2H);13C NMR(101MHz,Chloroform-d)δ142.26,135.56,129.54,128.90,128.45,127.92,127.76,127.06,119.74,48.37,35.77,28.27,27.59,25.21,17.11;HRMS(ESI):m/z calcd for C11H13NSe[M+Na]+366.0736,found 366.0733.
实施例27:4-(对甲苯基硒基)丁腈的制备
在惰性气体保护下,称取氯化亚铁(5.1mg,20mol%)、1,10-菲罗啉(7.2mg,20mol%)、1,4-二氧六环(6mL)加入史莱克管中,加热至80℃搅拌反应0.5h,冷却至室温后直接用于下一步。在装有催化剂-配体络合物的史莱克管中仍然在惰性气体保护下加入环丁酮O-全氟苯甲酰肟(55.8mg,0.2mmol),二(4-甲基苯基)二硒醚(102.6mg,1.5equiv),三乙胺(202.4mg,10equiv)。室温搅拌反应24h。所得反应物用硅胶柱(石油醚/乙酸乙酯)纯化得到4-(对甲苯基硒基)丁腈(40.2mg)产率84%。
4-(对甲苯基硒基)丁腈
1H NMR(600MHz,Chloroform-d)δ7.41(d,J=8.0Hz,2H),7.10(d,J=7.8Hz,2H),2.94(t,J=7.0Hz,2H),2.49(t,J=7.1Hz,2H),2.33(s,3H),1.97(p,J=7.0Hz,2H);13C NMR(151MHz,Chloroform-d)δ137.9,133.9,130.3,124.9,119.2,26.5,25.8,21.3,17.1;HRMS(ESI):m/z calcd for C11H13NSe[M+H]+240.0291,found 240.0292.
实施例28:4-((4-氟苯基)硒基)丁腈的制备
在惰性气体保护下,称取氯化亚铁(5.1mg,20mol%)、1,10-菲罗啉(7.2mg,20mol%)、1,4-二氧六环(6mL)加入史莱克管中,加热至80℃搅拌反应0.5h,冷却至室温后直接用于下一步。在装有催化剂-配体络合物的史莱克管中仍然在惰性气体保护下加入环丁酮O-全氟苯甲酰肟(55.8mg,0.2mmol),二(4-氟苯基)二硒醚(105.0mg,1.5equiv),三乙胺(202.4mg,10equiv)。室温搅拌反应24h。所得反应物用硅胶柱(石油醚/乙酸乙酯)纯化得到4-((4-氟苯基)硒基)丁腈(26.0mg)产率54%。
4-((4-氟苯基)硒基)丁腈
1H NMR(600MHz,Chloroform-d)δ7.56–7.46(m,2H),7.04–6.94(m,2H),2.94(t,J=7.0Hz,2H),2.50(t,J=7.0Hz,2H),1.97(p,J=7.0Hz,2H);13C NMR(151MHz,Chloroform-d)δ162.8(d,J=247.9Hz),136.1(d,J=7.9Hz),123.2(d,J=3.3Hz),119.1,116.7(d,J=21.5Hz),27.0,25.8,17.1;19F NMR(376MHz,Chloroform-d)δ-113.70;HRMS(ESI):m/zcalcd for C10H10FNSe[M+H]+244.0040,found 244.0042.
实施例29:4-(甲基硒基)丁腈的制备
在惰性气体保护下,称取氯化亚铁(5.1mg,20mol%)、1,10-菲罗啉(7.2mg,20mol%)、1,4-二氧六环(6mL)加入史莱克管中,加热至80℃搅拌反应0.5h,冷却至室温后直接用于下一步。在装有催化剂-配体络合物的史莱克管中仍然在惰性气体保护下加入环丁酮O-全氟苯甲酰肟(55.8mg,0.2mmol),二甲基二硒醚(57.0mg,1.5equiv),三乙胺(202.4mg,10equiv)。室温搅拌反应24h。所得反应物用硅胶柱(石油醚/乙酸乙酯)纯化得到4-(甲基硒基)丁腈(18.1mg)产率56%。
4-(甲基硒基)丁腈
1H NMR(600MHz,Chloroform-d)δ2.66(t,J=7.0Hz,2H),2.52(t,J=7.0Hz,2H),2.07–1.96(m,5H);13C NMR(151MHz,Chloroform-d)δ119.3,25.7,23.6,17.2,4.4.
实施例30:4-(苄基硒基)丁腈的制备
在惰性气体保护下,称取氯化亚铁(5.1mg,20mol%)、1,10-菲罗啉(7.2mg,20mol%)、1,4-二氧六环(6mL)加入史莱克管中,加热至80℃搅拌反应0.5h,冷却至室温后直接用于下一步。在装有催化剂-配体络合物的史莱克管中仍然在惰性气体保护下加入环丁酮O-全氟苯甲酰肟(55.8mg,0.2mmol),二苄基二硒醚(102.6mg,1.5equiv),三乙胺(202.4mg,10equiv)。室温搅拌反应24h。所得反应物用硅胶柱(石油醚/乙酸乙酯)纯化得到4-(苄基硒基)丁腈(30.4mg)产率64%。
4-(苄基硒基)丁腈
1H NMR(600MHz,Chloroform-d)δ7.28(dt,J=10.6,7.2Hz,4H),7.21(t,J=6.9Hz,1H),3.77(s,2H),2.57(t,J=7.0Hz,2H),2.39(d,J=14.1Hz,2H),1.87(p,J=7.1Hz,2H);13C NMR(151MHz,Chloroform-d)δ138.9,128.9,128.8,127.1,119.2,27.4,25.9,22.1,17.2.
对所公开的实施例的上述说明,使本领域专业技术人员能够实现或使用本发明。对这些实施例的多种修改对本领域的专业技术人员来说将是显而易见的,本文中所定义的一般原理可以在不脱离本发明的精神或范围的情况下,在其它实施例中实现。因此,本发明将不会被限制于本文所示的这些实施例,而是要符合与本文所公开的原理和新颖特点相一致的最宽的范围。
Claims (2)
1.一种有机硒化合物的合成方法,其特征在于,所述方法具体包括如下步骤:
(1)向25毫升的史莱克管中加入催化剂、配体和有机溶剂,搅拌得反应溶剂,备用;
(2)待步骤(1)反应溶剂冷却至室温后,继续向25毫升的史莱克管中添加肟酯、二硒化物和碱反应;并于反应过程中用TLC进行跟踪以决定具体的反应时间;
(3)待步骤(2)的反应结束后,将溶剂旋干,并用硅胶柱进行纯化得到所述有机硒化合物,即为有机硒吡咯啉衍生物与有机硒烷基腈衍生物;
步骤(1)中的搅拌温度为80℃,搅拌时间为30min;步骤(2)中的反应温度为90℃,反应时间为12-24h;
所述肟酯为1-苯基戊-4-烯-1-酮O-全氟苯甲酰肟、1-(4-氯苯基)戊-4-烯-1-酮O-全氟苯甲酰肟、1-(4-甲氧基苯基)戊-4-烯-1-酮O-全氟苯甲酰肟、1-(3-氯苯基)戊-4-烯-1-酮O-全氟苯甲酰肟、1-(3-甲氧基苯基)戊-4-烯-1-酮O-全氟苯甲酰肟、1-(噻吩-2-基)戊-4-烯-1-酮O-全氟苯甲酰肟、1-(呋喃-2-基)戊-4-烯-1-酮O-全氟苯甲酰肟、1-苯基十六烷-4-烯-1-酮O-全氟苯甲酰肟、5-甲基-1-苯基十六烷-4-烯-1-酮O-全氟苯甲酰肟、4-甲基-1-苯基戊-4-烯-1-酮O-全氟苯甲酰肟、2-烯丙基-3,4-二氢萘-1(2H)-酮-O-全氟苯甲酰肟、环丁酮 O-全氟苯甲酰肟、3-苯基环丁烷-1-酮O-全氟苯甲酰肟、乙基-3-(((全氟苯甲酰)氧基)亚氨基)环丁烷-1-羧酸酯、2-甲基环丁烷-1-酮O-全氟苯甲酰肟、3-氧杂环丁酮O-全氟苯甲酰肟、3-硫杂环丁酮O-全氟苯甲酰肟、2-甲基环戊烷-1-酮O-全氟苯甲酰肟、2-苯基环己-1-酮O-全氟苯甲酰肟、2-苯基环庚烷-1-酮O-全氟苯甲酰肟;
所述二硒化物为二苯基二硒醚、二(4-甲氧基苯基)二硒醚、二(4-氟苯基)二硒醚、二苄基二硒醚、二甲基二硒醚、二(4-甲基苯基)二硒醚;
所述肟酯在反应溶剂中的摩尔浓度为0.2 mmol/mL,及所述有机溶剂为1,4-二氧六环,且所述有机溶剂的用量为6mL;
所述催化剂为双-(1,5-环辛二烯镍)或氯化亚铁,及所述催化剂的用量为肟酯用量的20mol%;所述配体为1,10-菲罗啉,且所述配体用量为肟酯用量的20mol%;
所述碱为三乙胺,碱的用量为肟酯用量的10e;肟酯与硒化试剂的摩尔比为2:1~1:2。
2.根据权利要求1所述的一种有机硒化合物的合成方法,其特征在于,所述步骤3)中的处理及纯化方法:先将反应后的溶剂旋干,进一步用柱层析法纯化分离;
其中,柱层析可以选择200~300目的硅胶作为固定相,展开剂为石油醚和乙酸乙酯的混合溶液。
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