CN109988117B - Preparation method of a class of 3-methylquinoxaline-2(1H)-one derivatives - Google Patents
Preparation method of a class of 3-methylquinoxaline-2(1H)-one derivatives Download PDFInfo
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- CN109988117B CN109988117B CN201910429014.8A CN201910429014A CN109988117B CN 109988117 B CN109988117 B CN 109988117B CN 201910429014 A CN201910429014 A CN 201910429014A CN 109988117 B CN109988117 B CN 109988117B
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- BMIMNRPAEPIYDN-UHFFFAOYSA-N 3-methyl-2-quinoxalinol Chemical class C1=CC=C2N=C(O)C(C)=NC2=C1 BMIMNRPAEPIYDN-UHFFFAOYSA-N 0.000 title claims abstract description 9
- 238000002360 preparation method Methods 0.000 title claims description 3
- ZBIKORITPGTTGI-UHFFFAOYSA-N [acetyloxy(phenyl)-$l^{3}-iodanyl] acetate Chemical compound CC(=O)OI(OC(C)=O)C1=CC=CC=C1 ZBIKORITPGTTGI-UHFFFAOYSA-N 0.000 claims abstract description 21
- -1 quinoxalinone compound Chemical class 0.000 claims abstract description 19
- 239000011941 photocatalyst Substances 0.000 claims abstract description 16
- 238000000034 method Methods 0.000 claims abstract description 11
- 238000006555 catalytic reaction Methods 0.000 claims abstract description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 22
- 239000000460 chlorine Substances 0.000 claims description 17
- 229920000604 Polyethylene Glycol 200 Polymers 0.000 claims description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 9
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 150000002367 halogens Chemical group 0.000 claims description 8
- 125000002252 acyl group Chemical group 0.000 claims description 7
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 4
- 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 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- ZBQZBWKNGDEDOA-UHFFFAOYSA-N eosin B Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC([N+]([O-])=O)=C(O)C(Br)=C1OC1=C2C=C([N+]([O-])=O)C(O)=C1Br ZBQZBWKNGDEDOA-UHFFFAOYSA-N 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 238000013032 photocatalytic reaction Methods 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- UKZQEOHHLOYJLY-UHFFFAOYSA-M ethyl eosin Chemical compound [K+].CCOC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C([O-])=C(Br)C=C21 UKZQEOHHLOYJLY-UHFFFAOYSA-M 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
- 239000011630 iodine Substances 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 claims description 2
- 229940043267 rhodamine b Drugs 0.000 claims description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims 1
- 239000000049 pigment Substances 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 45
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- 125000000524 functional group Chemical group 0.000 abstract description 2
- 238000009776 industrial production Methods 0.000 abstract 1
- 239000002994 raw material Substances 0.000 abstract 1
- 238000010189 synthetic method Methods 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 38
- 239000000047 product Substances 0.000 description 35
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
- 239000002904 solvent Substances 0.000 description 18
- 239000012043 crude product Substances 0.000 description 13
- 238000000605 extraction Methods 0.000 description 13
- SKTCDJAMAYNROS-UHFFFAOYSA-N methoxycyclopentane Chemical compound COC1CCCC1 SKTCDJAMAYNROS-UHFFFAOYSA-N 0.000 description 13
- 239000003208 petroleum Substances 0.000 description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 229910052799 carbon Inorganic materials 0.000 description 12
- 239000003480 eluent Substances 0.000 description 12
- 238000003818 flash chromatography Methods 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- 238000001228 spectrum Methods 0.000 description 12
- FFRYUAVNPBUEIC-UHFFFAOYSA-N quinoxalin-2-ol Chemical class C1=CC=CC2=NC(O)=CN=C21 FFRYUAVNPBUEIC-UHFFFAOYSA-N 0.000 description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- 229940079593 drug Drugs 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- 238000001819 mass spectrum Methods 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- 230000003595 spectral effect Effects 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 230000002194 synthesizing effect Effects 0.000 description 3
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 2
- LEFAAJZDPNMPLQ-UHFFFAOYSA-N 1-methyl-7-(trifluoromethyl)quinoxalin-2-one Chemical compound FC(F)(F)C1=CC=C2N=CC(=O)N(C)C2=C1 LEFAAJZDPNMPLQ-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 125000006165 cyclic alkyl group Chemical group 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 238000005265 energy consumption Methods 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical compound [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 description 2
- 238000007069 methylation reaction Methods 0.000 description 2
- 239000012429 reaction media Substances 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- IVURBRPZGWNNLH-UHFFFAOYSA-N 1,3,6,7-tetramethylquinoxalin-2-one Chemical compound N1=C(C)C(=O)N(C)C2=C1C=C(C)C(C)=C2 IVURBRPZGWNNLH-UHFFFAOYSA-N 0.000 description 1
- MTAYAONIFFKJJF-UHFFFAOYSA-N 1,3-dimethyl-6-nitroquinoxalin-2-one Chemical compound [O-][N+](=O)C1=CC=C2N(C)C(=O)C(C)=NC2=C1 MTAYAONIFFKJJF-UHFFFAOYSA-N 0.000 description 1
- GRGDSEWMSMJHMU-UHFFFAOYSA-N 1,3-dimethylquinoxalin-2-one Chemical compound C1=CC=C2N(C)C(=O)C(C)=NC2=C1 GRGDSEWMSMJHMU-UHFFFAOYSA-N 0.000 description 1
- DRDHXUCEJHWQON-UHFFFAOYSA-N 1,6,7-trimethylquinoxalin-2-one Chemical compound N1=CC(=O)N(C)C2=C1C=C(C)C(C)=C2 DRDHXUCEJHWQON-UHFFFAOYSA-N 0.000 description 1
- FJLBBMABBOQQAJ-UHFFFAOYSA-N 1-benzyl-3-methylquinoxalin-2-one Chemical compound O=C1C(C)=NC2=CC=CC=C2N1CC1=CC=CC=C1 FJLBBMABBOQQAJ-UHFFFAOYSA-N 0.000 description 1
- XSIQIJZHBWPBDQ-UHFFFAOYSA-N 1-benzylquinoxalin-2-one Chemical compound O=C1C=NC2=CC=CC=C2N1CC1=CC=CC=C1 XSIQIJZHBWPBDQ-UHFFFAOYSA-N 0.000 description 1
- YEGRUCPCVUDQCF-UHFFFAOYSA-N 1-methyl-6-nitroquinoxalin-2-one Chemical compound C1=C([N+]([O-])=O)C=C2N=CC(=O)N(C)C2=C1 YEGRUCPCVUDQCF-UHFFFAOYSA-N 0.000 description 1
- CHPVQLYVDDOWNT-UHFFFAOYSA-N 1-methylquinoxalin-2-one Chemical compound C1=CC=C2N=CC(=O)N(C)C2=C1 CHPVQLYVDDOWNT-UHFFFAOYSA-N 0.000 description 1
- GFZURTHPGYNOOL-UHFFFAOYSA-N 1-phenylquinoxalin-2-one Chemical compound O=C1C=NC2=CC=CC=C2N1C1=CC=CC=C1 GFZURTHPGYNOOL-UHFFFAOYSA-N 0.000 description 1
- DGKOFMLBEWYZLR-UHFFFAOYSA-N 1-prop-2-ynylquinoxalin-2-one Chemical compound C1=CC=C2N(CC#C)C(=O)C=NC2=C1 DGKOFMLBEWYZLR-UHFFFAOYSA-N 0.000 description 1
- WWQICOXCMRQCHP-UHFFFAOYSA-N 3-methyl-1-phenylquinoxalin-2-one Chemical compound O=C1C(C)=NC2=CC=CC=C2N1C1=CC=CC=C1 WWQICOXCMRQCHP-UHFFFAOYSA-N 0.000 description 1
- CHGWIDJZBJRMMI-UHFFFAOYSA-N 3-methyl-1-prop-2-ynylquinoxalin-2-one Chemical compound C1=CC=C2N(CC#C)C(=O)C(C)=NC2=C1 CHGWIDJZBJRMMI-UHFFFAOYSA-N 0.000 description 1
- KUKQPMCYLSKEIE-UHFFFAOYSA-N 6-bromo-1,3-dimethylquinoxalin-2-one Chemical compound BrC1=CC=C2N(C)C(=O)C(C)=NC2=C1 KUKQPMCYLSKEIE-UHFFFAOYSA-N 0.000 description 1
- RILVWEDHGCCKLS-UHFFFAOYSA-N 6-bromo-1-methylquinoxalin-2-one Chemical compound C1=C(Br)C=C2N=CC(=O)N(C)C2=C1 RILVWEDHGCCKLS-UHFFFAOYSA-N 0.000 description 1
- ZFNRTLFONAUWQD-UHFFFAOYSA-N 7-fluoro-1,3-dimethylquinoxalin-2-one Chemical compound FC1=CC=C2N=C(C(N(C2=C1)C)=O)C ZFNRTLFONAUWQD-UHFFFAOYSA-N 0.000 description 1
- STYKWDCQOONTBY-UHFFFAOYSA-N 7-fluoro-1-methylquinoxalin-2-one Chemical compound FC=1C=C2N(C(C=NC2=CC=1)=O)C STYKWDCQOONTBY-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
- 229940125895 MET kinase inhibitor Drugs 0.000 description 1
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 238000006254 arylation reaction Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- MNJVRJDLRVPLFE-UHFFFAOYSA-N etoricoxib Chemical compound C1=NC(C)=CC=C1C1=NC=C(Cl)C=C1C1=CC=C(S(C)(=O)=O)C=C1 MNJVRJDLRVPLFE-UHFFFAOYSA-N 0.000 description 1
- 229960004945 etoricoxib Drugs 0.000 description 1
- 239000000576 food coloring agent Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000004896 high resolution mass spectrometry Methods 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- MBXNQZHITVCSLJ-UHFFFAOYSA-N methyl fluorosulfonate Chemical group COS(F)(=O)=O MBXNQZHITVCSLJ-UHFFFAOYSA-N 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 238000012803 optimization experiment Methods 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000001699 photocatalysis Effects 0.000 description 1
- 238000007146 photocatalysis Methods 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
- 229960002855 simvastatin Drugs 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000006692 trifluoromethylation reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
- C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
- C07D241/40—Benzopyrazines
- C07D241/44—Benzopyrazines with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
Abstract
本发明公开了一种3‑甲基喹喔啉‑2(1H)‑酮类化合物的制备方法,该方法是将喹喔啉酮类化合物与二乙酸碘苯在光催化剂作用下进行可见光催化反应,即得3‑甲基喹喔啉酮类化合物;相对现有技术,该合成方法的优势有:1)使用的喹喔啉‑2(1H)‑酮衍生物原料廉价易得,有利于降低成本,2)在室温下经光照就可进行反应,条件温和,且一步得到产物,反应收率高,操作环保,有利于工业生产,3)该方法对官能团适用性好,可以获得各种3‑甲基喹喔啉酮类化合物衍生物。The invention discloses a method for preparing a 3-methylquinoxaline-2(1H)-ketone compound. The method comprises the following steps of performing a visible light catalytic reaction between a quinoxalinone compound and iodobenzene diacetate under the action of a photocatalyst , that is, 3-methylquinoxalinone compounds are obtained; relative to the prior art, the synthetic method has the following advantages: 1) the quinoxaline-2(1H)-ketone derivative raw materials used are cheap and easy to obtain, which is conducive to reducing cost, 2) the reaction can be carried out by light at room temperature, the conditions are mild, and the product can be obtained in one step, the reaction yield is high, the operation is environmentally friendly, which is beneficial to industrial production, 3) the method has good applicability to functional groups, and can obtain various 3 - Methylquinoxalinone derivatives.
Description
技术领域technical field
本发明涉及一种喹喔啉酮类衍生物的合成方法,特别涉及以喹喔啉-2(1H)-酮类化合物与二乙酸碘苯为起始原料,在光催化剂作用下,经光催化一步制备3-甲基喹喔啉-2(1H)-酮的方法,属于有机合成技术领域。The invention relates to a method for synthesizing quinoxalinone derivatives, in particular to a method for synthesizing quinoxalin-2(1H)-one compounds and iodobenzene diacetate as starting materials, under the action of a photocatalyst, through photocatalysis A method for preparing 3-methylquinoxalin-2(1H)-one in one step belongs to the technical field of organic synthesis.
背景技术Background technique
甲基是最小的烷基片段,大多数药物分子中都有这一基团,在分子中引入甲基可以改善药物分子的药物溶解性,选择性和代谢活性。在代谢位点的邻位引入甲基,产生空间位阻,可以延长药物半衰期,如辛伐他汀,若药物半衰期太长,药物化学家还能通过引入甲基产生新的代谢位点,缩短药物半衰期,如依托考昔,甲基在药物化学中的影响被称为“magic methyl effect”。Methyl group is the smallest alkyl fragment, which is present in most drug molecules. The introduction of methyl group into the molecule can improve the drug solubility, selectivity and metabolic activity of drug molecules. Introducing a methyl group at the vicinal position of the metabolic site creates steric hindrance, which can prolong the half-life of the drug, such as simvastatin. If the half-life of the drug is too long, medicinal chemists can also introduce a methyl group to generate a new metabolic site to shorten the drug. Half-life, like etoricoxib, the effect of methyl in medicinal chemistry is known as the "magic methyl effect".
喹喔啉-2(1H)-酮作为一类重要的氮杂环衍生物,其在天然产物,药剂学以及材料科学中的应用已经非常普遍,其中3-甲基喹喔啉-2(1H)-酮衍生物因为其具有可以调控喹喔啉酮生物活性的特性更是吸引了一大批有机化学研究学者的兴趣。例如,化合物A是一种c-met激酶抑制剂(Bioorg.Med.Chem.2015,23,6560),甲基的引入明显改善了该分子的药物活性。As an important class of nitrogen heterocyclic derivatives, quinoxalin-2(1H)-ones have been widely used in natural products, pharmacy and materials science. Among them, 3-methylquinoxaline-2(1H) )-ketone derivatives have attracted the interest of a large number of organic chemistry researchers because of their ability to control the biological activity of quinoxalinone. For example, compound A is a c-met kinase inhibitor (Bioorg. Med. Chem. 2015, 23, 6560), and the introduction of methyl groups significantly improved the drug activity of the molecule.
目前喹喔啉-2(1H)-酮C3位的芳基化、酰化、磷酸酯化、氨化以及三氟甲基化等研究都有相关报道,但是关于喹喔啉-2(1H)-酮类化合物C3位直接甲基化却还未见相关报道。At present, there are relevant reports on the arylation, acylation, phosphorylation, amination and trifluoromethylation of the C3 position of quinoxaline-2(1H)-one. - The direct methylation of the C3 position of ketone compounds has not been reported yet.
发明内容SUMMARY OF THE INVENTION
针对现有技术中对喹喔啉-2(1H)-酮的C3位烷基化反应存在的技术空白,本发明的目的是在于提供一种利用光催化反应在温和条件下实现3-甲基喹喔啉-2(1H)-酮及其衍生物的合成方法,该方法通过使用光催化剂从而避免使用对环境有污染的金属催化剂,同时在常温光照等温和条件下反应,避免高温和其他繁复的操作,且能降低反应成本和能耗,提高反应的效率同时达到绿化化学的目的。Aiming at the technical gap existing in the prior art for the C3 alkylation reaction of p-quinoxalin-2(1H)-one, the object of the present invention is to provide a kind of photocatalytic reaction to realize 3-methyl group under mild conditions A method for synthesizing quinoxalin-2(1H)-one and its derivatives, the method avoids the use of metal catalysts that pollute the environment by using photocatalysts, and at the same time reacts under mild conditions such as light at room temperature, avoiding high temperature and other complicated It can reduce the cost and energy consumption of the reaction, improve the efficiency of the reaction and achieve the purpose of greening chemistry.
为了实现上述技术目的,本发明提供了一种3-甲基喹喔啉-2(1H)-酮类化合物的制备方法,式1结构喹喔啉酮类化合物与式2二乙酸碘苯及光催化剂作用下进行可见光催化反应,即得式3结构3-甲基喹喔啉酮类化合物;In order to achieve the above technical purpose, the present invention provides a preparation method of a 3-methylquinoxaline-2(1H)-one compound, the quinoxalinone compound of formula 1 and the iodobenzene diacetate of formula 2 and a light Under the action of a catalyst, a visible light catalytic reaction is carried out to obtain a 3-methylquinoxalinone compound of formula 3;
其中,in,
R1为氢、烷基或芳烷基;R 1 is hydrogen, alkyl or aralkyl;
R2和R3独立选择氢、烷基、烷氧基、硝基、氨基、酰基、卤素取代基、羟基、氰基或三氟甲基。R2 and R3 are independently selected from hydrogen , alkyl, alkoxy, nitro, amino, acyl, halogen substituent, hydroxy, cyano or trifluoromethyl.
本发明的式1、式2和式3化合物中。R1是氮原子上取代的基团,其可以选择为氢原子,也可以是其他基团取代氢原子,如烷基或芳烷基取代氢。烷基为C1~C8的烷基,可以为直链烷基或者带支链的烷基,或者是环状烷基,具体如甲基、乙基、丁基、异丙基、环己基等等。芳烷基主要是烷基的烷基链上取代有芳基,烷基链的长度为C1~C8,在烷基链的任意碳原子上取代芳基,芳基如苯基、萘基或取代苯基,取代苯基是苯环上含有一些常规的取代基,如C1~C5的烷基、C1~C5的烷氧基、卤素取代基等,最常见的芳烷基如苄基、苯基乙基等等。R2和R3是喹喔啉酮类化合物的苯环上包含的取代基团,R2和R3对喹喔啉酮类化合物C3位烷基化反应影响相对较小,其取代位置可以是苯环上可以取代的任意位置,且其选择范围较广,如氢、烷基、烷氧基、硝基、氨基、酰基、卤素取代基、羟基、氰基或三氟甲基等,当R2或R3选择烷基时,烷基为C1~C8的烷基,可以为直链烷基或者为带支链的烷基,或者是环状烷基,具体如甲基、乙基、丁基、异丙基、环己基等等;R2或R3选择烷氧基时,烷氧基为C1~C8的烷氧基,如甲氧基、乙氧基、异丁氧基等等;R2或R3选择酰基时,酰基为甲酰基、乙酰基或丙酰基;R2或R3选择卤素取代基时,卤素取代基为氟、氯、溴或碘。In the compounds of formula 1, formula 2 and formula 3 of the present invention. R 1 is a group substituted on a nitrogen atom, which can be selected to be a hydrogen atom, or other groups to replace the hydrogen atom, such as alkyl or aralkyl to replace the hydrogen. The alkyl group is a C 1 -C 8 alkyl group, which can be a straight-chain alkyl group or a branched-chain alkyl group, or a cyclic alkyl group, such as methyl, ethyl, butyl, isopropyl, and cyclohexyl. and many more. Aralkyl is mainly an aryl group substituted on the alkyl chain of an alkyl group, the length of the alkyl chain is C 1 -C 8 , and an aryl group is substituted on any carbon atom of the alkyl chain, such as phenyl and naphthyl. Or substituted phenyl, substituted phenyl contains some conventional substituents on the benzene ring, such as C 1 -C 5 alkyl, C 1 -C 5 alkoxy, halogen substituents, etc., the most common aralkyl Such as benzyl, phenylethyl and the like. R 2 and R 3 are substituent groups contained on the benzene ring of quinoxalinone compounds, R 2 and R 3 have relatively little effect on the alkylation reaction of quinoxalinone compounds at C3 position, and their substitution positions can be Any position that can be substituted on the benzene ring, and its selection range is wide, such as hydrogen, alkyl, alkoxy, nitro, amino, acyl, halogen substituent, hydroxyl, cyano or trifluoromethyl, etc., when R When 2 or R 3 selects an alkyl group, the alkyl group is a C 1 -C 8 alkyl group, which can be a straight-chain alkyl group or a branched-chain alkyl group, or a cyclic alkyl group, such as methyl, ethyl , butyl, isopropyl, cyclohexyl, etc.; when R 2 or R 3 selects an alkoxy group, the alkoxy group is a C 1 -C 8 alkoxy group, such as methoxy, ethoxy, isobutoxy When R 2 or R 3 selects an acyl group, the acyl group is formyl, acetyl or propionyl; when R 2 or R 3 selects a halogen substituent, the halogen substituent is fluorine, chlorine, bromine or iodine.
优选的方案,喹喔啉-2-酮类衍生物与二乙酸碘苯的摩尔比为:1:1~1:20。较优选为1:1~1:10。In a preferred solution, the molar ratio of the quinoxalin-2-one derivatives to iodobenzene diacetate is 1:1 to 1:20. More preferably, it is 1:1 to 1:10.
优选的方案,喹喔啉-2-酮类衍生物与光催化剂的摩尔比为:1:0.01~1:0.05。In a preferred solution, the molar ratio of the quinoxalin-2-one derivatives to the photocatalyst is: 1:0.01-1:0.05.
较优选的方案,所述光催化剂包括Ru(bpy)3Cl2、曙红B(C20H6Br2N2Na2O9)、水溶伊红(曙红Y,C20H6Br4Na3O5)、醇溶伊红、罗丹明B、食用色素红中至少一种。最优选的光催化剂为Ru(bpy)3Cl2。In a more preferred solution, the photocatalyst includes Ru(bpy) 3 Cl 2 , eosin B (C 20 H 6 Br 2 N 2 Na 2 O 9 ), water-soluble eosin (eosin Y, C 20 H 6 Br 4 ) At least one of Na 3 O 5 ), alcohol-soluble eosin, rhodamine B, and food coloring red. The most preferred photocatalyst is Ru(bpy) 3Cl2 .
优选的方案,所述可见光催化反应的条件为:在可见光照射下,于室温反应6~12小时。In a preferred solution, the conditions for the visible light catalytic reaction are: under visible light irradiation, the reaction is performed at room temperature for 6 to 12 hours.
优选的方案,所述可见光源为功率为3W~24W的LED白光源、蓝光源或绿色光源。较优选的可见光源为功率为12W的LED白光源。In a preferred solution, the visible light source is an LED white light source, a blue light source or a green light source with a power of 3W to 24W. A more preferred visible light source is an LED white light source with a power of 12W.
优选的方案,所述光催化反应在DMSO、DMF、CHCl3、CH3OH、PEG-200、PEG-400中至少一种反应介质中进行。较优选的反应介质为PEG-200。In a preferred solution, the photocatalytic reaction is carried out in at least one reaction medium among DMSO, DMF, CHCl 3 , CH 3 OH, PEG-200, and PEG-400. A more preferred reaction medium is PEG-200.
本发明的3-甲基喹啉-2(1H)-酮类化合物的合成路线如下:The synthetic route of the 3-methylquinoline-2(1H)-one compound of the present invention is as follows:
本发明的3-甲基喹喔啉-2(1H)-酮类化合物的合成反应机理如下:光催化剂被光激活释放电子,释放的电子被二乙酸碘苯捕获,捕获电子的二乙酸碘苯通过裂解释放甲基自由基,甲基自由基进攻喹喔啉酮类化合物的3位碳,形成中间体A,中间体A被光催化剂夺回电子转化成不稳定的中间体B,中间体B发生分子内重组并释放氢质子,得到目标化合物。The synthesis reaction mechanism of the 3-methylquinoxaline-2(1H)-one compounds of the present invention is as follows: the photocatalyst is activated by light to release electrons, the released electrons are captured by iodobenzene diacetate, and the captured electron iodobenzene diacetate The methyl radical is released by cleavage, and the methyl radical attacks the 3-position carbon of quinoxalinones to form intermediate A, which is converted into unstable intermediate B by recapturing electrons by the photocatalyst, and intermediate B occurs Intramolecular recombination and release of hydrogen protons yield the target compound.
相对现有技术,本发明的技术方案带来的有益技术效果:Relative to the prior art, the beneficial technical effects brought by the technical solution of the present invention:
本发明的通过使用绿色环保的光催化剂从而避免使用对环境有污染的金属催化剂。The present invention avoids the use of metal catalysts that pollute the environment by using green and environment-friendly photocatalysts.
本发明的喹喔啉酮类化合物C3甲基化反应效率高,可以获得高选择性收率。The quinoxalinone compound C3 methylation reaction efficiency of the present invention is high, and high selectivity yield can be obtained.
本发明的反应条件温和,可以常温光照等温和条件下反应,避免高温和其他繁复的操作,且降低反应成本和能耗。The reaction conditions of the invention are mild, and the reaction can be carried out under mild conditions such as normal temperature and illumination, avoiding high temperature and other complicated operations, and reducing the reaction cost and energy consumption.
本发明对官能团适用性好,可以获得各种3-甲基喹喔啉酮类化合物衍生物,为喹喔啉酮类化合物衍生物的合成提供了一种全新的路径。The invention has good applicability to functional groups, can obtain various 3-methylquinoxalinone compound derivatives, and provides a brand-new route for the synthesis of quinoxalinone compound derivatives.
具体实施方式Detailed ways
以下实施例旨在进一步说明本发明内容,而不是限制本发明权利要求保护范围。The following examples are intended to further illustrate the content of the present invention, rather than limit the protection scope of the claims of the present invention.
条件优化实验:Condition optimization experiment:
具体反应条件按以下进行:在25℃下,在10mL反应管中,依次加入化合物1a(0.2mmol),二乙酸碘苯2a(0.44mmol),光催化剂,溶剂(1mL),混合均匀,然后在12w白色LED灯照射下,搅拌反应8h。用TLC检测至反应完成后,加入环戊基甲醚(2ml×3)萃取,取上层萃取液,50℃下真空浓缩至无溶剂,得到粗产品,然后用体积比为2:1的石油醚和乙酸乙酯混合洗脱剂冲洗,硅胶柱快速柱层析,得到产物3aa。The specific reaction conditions are as follows: at 25 ° C, in a 10 mL reaction tube, add compound 1a (0.2 mmol), iodobenzene diacetate 2a (0.44 mmol), photocatalyst, solvent (1 mL), mix well, and then in Under the irradiation of 12w white LED lamp, the reaction was stirred for 8h. After the reaction was detected by TLC, cyclopentyl methyl ether (2ml×3) was added for extraction, and the upper layer extract was taken and concentrated in vacuo to no solvent at 50°C to obtain a crude product, which was then used with petroleum ether in a volume ratio of 2:1. Rinse with mixed eluent with ethyl acetate, and perform flash column chromatography on silica gel to obtain product 3aa.
为了高产率得到3-甲基-2(1H)-喹喔啉酮类化合物,根据上述反应条件进行以下对照实验组1~13,对影响反应的一些条件因素进行了考察,主要包括光催化剂的种类、溶剂,具体优化过程见下表:In order to obtain 3-methyl-2(1H)-quinoxalinone compounds in high yield, the following control experiment groups 1 to 13 were carried out according to the above reaction conditions, and some conditional factors affecting the reaction were investigated, mainly including the photocatalyst Types, solvents, and the specific optimization process are shown in the following table:
从上表中可以看出,在所有实验采用的光催化剂中Ru(bpy)3Cl2、曙红B、水溶伊红等光催化剂都可以实现3-甲基-2(1H)-喹喔啉酮类化合物的合成,但是Ru(bpy)3Cl2具有最佳的催化效果。且催化剂的用量在1%左右就可以达到很好的催化效果。对于溶剂的选择,最佳的溶剂为PEG-200;其次,DMF和DMSO也是反应较好的良性溶剂,而乙腈,四氢呋喃及二氯乙烷作为溶剂几乎得不到目标产物。It can be seen from the above table that among all the photocatalysts used in the experiments, Ru(bpy) 3 Cl 2 , eosin B, water-soluble eosin and other photocatalysts can achieve 3-methyl-2(1H)-quinoxaline Synthesis of ketones, but Ru(bpy ) 3Cl2 has the best catalytic effect. And the amount of the catalyst is about 1% to achieve a good catalytic effect. For the choice of solvent, the best solvent is PEG-200; secondly, DMF and DMSO are also good solvents for reaction, while acetonitrile, tetrahydrofuran and dichloroethane can hardly obtain the target product.
以下具体实施案例1~12均是在优化条件下反应,考察不同取代基团对反应的影响。The following specific implementation cases 1 to 12 are all reacted under optimized conditions, and the influence of different substituent groups on the reaction is investigated.
实施例1Example 1
在25℃下,在10mL反应管中,依次加入1-甲基喹喔啉-2(1H)-酮1a(0.2mmol),二乙酸碘苯2a(0.44mmol),Ru(bpy)3Cl2·6H2O(0.002mmol),PEG-200(1mL),混合均匀,然后在12w白色LED灯照射下,搅拌反应8h。用TLC检测至反应完成后,加入环戊基甲醚(2ml×3)萃取,取上层萃取液,50℃下真空浓缩至无溶剂,得到粗产品,然后用体积比为2:1的石油醚和乙酸乙酯混合洗脱剂冲洗,硅胶柱快速柱层析,得到本实例中的1,3-二甲基喹喔啉-2(1H)-酮产物3aa,为白色固体32.8mg,收率91%。At 25°C, in a 10 mL reaction tube, sequentially add 1-methylquinoxalin-2(1H)-one 1a (0.2 mmol), iodobenzene diacetate 2a (0.44 mmol), Ru(bpy) 3 Cl 2 · 6H 2 O (0.002 mmol), PEG-200 (1 mL), mixed well, and then stirred for 8 h under the irradiation of a 12w white LED lamp. After the reaction was detected by TLC, cyclopentyl methyl ether (2ml×3) was added for extraction, and the upper layer extract was taken and concentrated in vacuo to no solvent at 50°C to obtain a crude product, which was then used with petroleum ether in a volume ratio of 2:1. The 1,3-dimethylquinoxalin-2(1H)-one product 3aa in this example was obtained as a white solid, 32.8 mg in a yield of 32.8 mg. 91%.
所得产物核磁图谱数据为:1H NMR(400MHz,CDCl3):δ=7.80(d,J=8.0Hz,1H),7.54–7.50(m,1H),7.35–7.29(m,2H),3.70(s,3H),2.60(s,3H);13C NMR(100MHz,CDCl3):δ=158.4,155.2,133.2,132.6,129.6,129.4,123.6,113.6,29.0,21.6.The nuclear magnetic spectrum data of the obtained product are: 1 H NMR (400MHz, CDCl 3 ): δ=7.80(d, J=8.0Hz, 1H), 7.54-7.50(m, 1H), 7.35-7.29(m, 2H), 3.70 (s, 3H), 2.60 (s, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ=158.4, 155.2, 133.2, 132.6, 129.6, 129.4, 123.6, 113.6, 29.0, 21.6.
实施例2Example 2
在25℃下,在10mL反应管中,依次加入6-溴-1-甲基喹喔啉-2(1H)-酮1b(0.2mmol),二乙酸碘苯2a(0.44mmol),Ru(bpy)3Cl2·6H2O(0.002mmol),PEG-200(1mL),混合均匀,然后在12W白色LED灯照射下,搅拌反应8h。用TLC检测至反应完成后,加入环戊基甲醚(2ml×3)萃取,取上层萃取液,50℃下真空浓缩至无溶剂,得到粗产品,然后用体积比为2:1的石油醚和乙酸乙酯混合洗脱剂冲洗,硅胶柱快速柱层析,得到本实例中的6-溴-1,3-二甲基喹喔啉-2(1H)-酮产物3ba,为白色固体42.8mg,收率85%。At 25°C, in a 10 mL reaction tube, sequentially add 6-bromo-1-methylquinoxalin-2(1H)-one 1b (0.2 mmol), iodobenzene diacetate 2a (0.44 mmol), Ru (bpy ) 3 Cl 2 ·6H 2 O (0.002 mmol), PEG-200 (1 mL), mixed uniformly, and then stirred for 8 h under the irradiation of a 12W white LED lamp. After the reaction was detected by TLC, cyclopentyl methyl ether (2ml×3) was added for extraction, and the upper layer extract was taken and concentrated in vacuo to no solvent at 50°C to obtain a crude product, which was then used with petroleum ether in a volume ratio of 2:1. Rinse with ethyl acetate mixed eluent, and perform flash column chromatography on silica gel to obtain 6-bromo-1,3-dimethylquinoxalin-2(1H)-one product 3ba in this example, which is a white solid 42.8 mg, the yield is 85%.
所得产物核磁图谱数据为:1H NMR(400MHz,CDCl3):δ=7.94(d,J=2.0Hz,1H),7.60(dd,J1=8.8Hz,J2=2.0Hz,1H),7.16(d,J=8.8Hz,1H),3.67(s,3H),2.59(s,3H);13CNMR(100MHz,CDCl3):δ=159.8,154.8,133.5,132.4,132.3,131.9,116.1,115.0,29.2,21.7。The nuclear magnetic spectrum data of the obtained product are: 1 H NMR (400 MHz, CDCl 3 ): δ=7.94 (d, J=2.0 Hz, 1H), 7.60 (dd, J 1 =8.8 Hz, J 2 =2.0 Hz, 1H), 7.16 (d, J=8.8 Hz, 1H), 3.67 (s, 3H), 2.59 (s, 3H); 13 CNMR (100 MHz, CDCl 3 ): δ=159.8, 154.8, 133.5, 132.4, 132.3, 131.9, 116.1 , 115.0, 29.2, 21.7.
所得产物高分辨质谱数据为:HRMS calc.for r C10H10BrN2O[M+H]+:252.9971,found 252.9968。The high-resolution mass spectrum data of the obtained product are: HRMS calc.for r C 10 H 10 BrN 2 O[M+H] + : 252.9971, found 252.9968.
实施例3Example 3
在25℃下,在10mL反应管中,依次加入7-氟-1-甲基喹喔啉-2(1H)-酮1c(0.2mmol),二乙酸碘苯2a(0.44mmol),Ru(bpy)3Cl2·6H2O(0.002mmol),PEG-200(1mL),混合均匀,然后在12W白色LED灯照射下,搅拌反应6h。用TLC检测至反应完成后,加入环戊基甲醚(2ml×3)萃取,取上层萃取液,50℃下真空浓缩至无溶剂,得到粗产品,然后用体积比为2:1的石油醚和乙酸乙酯混合洗脱剂冲洗,硅胶柱快速柱层析,得到本实例中的7-氟-1,3-二甲基喹喔啉-2(1H)-酮产物3ca,为白色固体35.3mg,收率92%。In a 10 mL reaction tube at 25°C, 7-fluoro-1-methylquinoxalin-2(1H)-one 1c (0.2 mmol), iodobenzene diacetate 2a (0.44 mmol), Ru (bpy ) 3 Cl 2 ·6H 2 O (0.002 mmol), PEG-200 (1 mL), mixed uniformly, and then stirred for 6 h under the irradiation of a 12W white LED lamp. After the reaction was detected by TLC, cyclopentyl methyl ether (2ml×3) was added for extraction, and the upper layer extract was taken and concentrated in vacuo to no solvent at 50°C to obtain a crude product, which was then used with petroleum ether in a volume ratio of 2:1. Rinse with ethyl acetate mixed eluent, and perform flash column chromatography on silica gel to obtain the 7-fluoro-1,3-dimethylquinoxalin-2(1H)-one product 3ca in this example, which is a white solid 35.3 mg, the yield is 92%.
所得产物核磁图谱数据为:1H NMR(400MHz,CDCl3):δ=7.79–7.76(m,1H),7.07–7.02(m,1H),6.98(dd,J1=10.0Hz,J2=2.4Hz,1H),3.66(s,3H),2.57(s,3H);13C NMR(100MHz,CDCl3):δ=164.1,161.6,157.2,155.1,134.7,134.6,131.3,131.2,129.4,,111.5,111.2,100.7,100.4,29.3,21.4;19F NMR(376MHz,CDCl3):δ=-108.3.The nuclear magnetic spectrum data of the obtained product are: 1 H NMR (400MHz, CDCl 3 ): δ=7.79-7.76 (m, 1H), 7.07-7.02 (m, 1H), 6.98 (dd, J 1 =10.0Hz, J 2 = 2.4Hz, 1H), 3.66(s, 3H), 2.57(s, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ=164.1, 161.6, 157.2, 155.1, 134.7, 134.6, 131.3, 131.2, 129.4, , 111.5, 111.2, 100.7, 100.4, 29.3, 21.4; 19 F NMR (376MHz, CDCl 3 ): δ=-108.3.
所得产物高分辨质谱数据为:HRMS(ESI)m/z calcd.for C10H10FN2O[M+H]+:193.0772,found 193.0770。The high-resolution mass spectrum data of the obtained product are: HRMS (ESI) m/z calcd.for C 10 H 10 FN 2 O[M+H] + : 193.0772, found 193.0770.
实施例4Example 4
在25℃下,在10mL反应管中,依次加入6-硝基-1-甲基喹喔啉-2(1H)-酮1d(0.2mmol),二乙酸碘苯2a(0.44mmol),Ru(bpy)3Cl2·6H2O(0.002mmol),PEG-200(1mL),混合均匀,然后在12W白光LED灯照射下,搅拌反应8h。用TLC检测至反应完成后,加入环戊基甲醚(2ml×3)萃取,取上层萃取液,50℃下真空浓缩至无溶剂,得到粗产品,然后用体积比为2:1的石油醚和乙酸乙酯混合洗脱剂冲洗,硅胶柱快速柱层析,得到本实例中的6-硝基-1,3-二甲基喹喔啉-2(1H)-酮产物3da,为黄色固体36.8mg,收率84%。In a 10 mL reaction tube at 25°C, 6-nitro-1-methylquinoxalin-2(1H)-one 1d (0.2 mmol), iodobenzene diacetate 2a (0.44 mmol), Ru ( bpy) 3 Cl 2 ·6H 2 O (0.002 mmol), PEG-200 (1 mL), mixed uniformly, and then stirred for 8 h under the irradiation of a 12W white LED lamp. After the reaction was detected by TLC, cyclopentyl methyl ether (2ml×3) was added for extraction, and the upper layer extract was taken and concentrated in vacuo to no solvent at 50°C to obtain a crude product, which was then used with petroleum ether in a volume ratio of 2:1. Rinse with ethyl acetate mixed eluent, silica gel column flash column chromatography to obtain 6-nitro-1,3-dimethylquinoxalin-2(1H)-one product 3da in this example as a yellow solid 36.8 mg, yield 84%.
所得产物核磁图谱数据为:1H NMR(400MHz,CDCl3):δ=8.69(d,J=2.4Hz,1H),8.38(dd,J1=9.2Hz,J2=2.4Hz,1H),7.39(d,J=9.2Hz,1H),3.75(s,3H),2.63(s,3H);13CNMR(100MHz,CDCl3):δ=161.2,154.8,143.4,137.9,131.8,125.2,124.2,114.2,29.6,21.7。The nuclear magnetic spectrum data of the obtained product are: 1 H NMR (400 MHz, CDCl 3 ): δ=8.69 (d, J=2.4 Hz, 1H), 8.38 (dd, J 1 =9.2 Hz, J 2 =2.4 Hz, 1H), 7.39 (d, J=9.2 Hz, 1H), 3.75 (s, 3H), 2.63 (s, 3H); 13 CNMR (100 MHz, CDCl 3 ): δ=161.2, 154.8, 143.4, 137.9, 131.8, 125.2, 124.2 , 114.2, 29.6, 21.7.
所得产物高分辨质谱数据为:HRMS(ESI)m/z calcd.for C10H10N3O3[M+H]+:220.0717,found 220.0713。The high-resolution mass spectral data of the obtained product are: HRMS (ESI) m/z calcd.for C 10 H 10 N 3 O 3 [M+H] + : 220.0717, found 220.0713.
实施例5Example 5
在25℃下,在10mL反应管中,依次加入7-三氟甲基-1-甲基喹喔啉-2(1H)-酮1e(0.2mmol),二乙酸碘苯2a(0.44mmol),Ru(bpy)3Cl2·6H2O(0.002mmol),PEG-200(1mL),混合均匀,然后在12W白色LED灯照射下,搅拌反应7h。用TLC检测至反应完成后,加入环戊基甲醚(2ml×3)萃取,取上层萃取液,50℃下真空浓缩至无溶剂,得到粗产品,然后用体积比为2:1的石油醚和乙酸乙酯混合洗脱剂冲洗,硅胶柱快速柱层析,得到本实例中的7-三氟甲基-1,3-二甲基喹喔啉-2(1H)-酮产物3ea,为白色固体43.6mg,收率90%。At 25°C, in a 10 mL reaction tube, 7-trifluoromethyl-1-methylquinoxalin-2(1H)-one 1e (0.2 mmol), and iodobenzene diacetate 2a (0.44 mmol) were sequentially added, Ru(bpy) 3 Cl 2 ·6H 2 O (0.002 mmol), PEG-200 (1 mL), mixed uniformly, and then stirred for 7 h under the irradiation of a 12W white LED lamp. After the reaction was detected by TLC, cyclopentyl methyl ether (2ml×3) was added for extraction, and the upper layer extract was taken and concentrated in vacuo to no solvent at 50°C to obtain a crude product, which was then used with petroleum ether in a volume ratio of 2:1. Rinse with ethyl acetate mixed eluent, silica gel column flash column chromatography to obtain 7-trifluoromethyl-1,3-dimethylquinoxalin-2(1H)-one product 3ea in this example, which is White solid 43.6 mg, yield 90%.
所得产物核磁图谱数据为:1H NMR(400MHz,CDCl3):δ=7.91(d,J=8.8Hz,1H),7.57(d,J=8.4Hz,1H),7.53(s,1H),3.73(s,3H),2.62(s,3H);13C NMR(100MHz,CDCl3):δ=161.2,154.9,134.3,133.3,132.0,131.3,131.0,130.2,125.0,122.3,120.2,120.1,111.0,29.2,21.8;19F NMR(376MHz,CDCl3):δ=-62.3。The nuclear magnetic spectrum data of the obtained product are: 1 H NMR (400MHz, CDCl 3 ): δ=7.91(d, J=8.8Hz, 1H), 7.57(d, J=8.4Hz, 1H), 7.53(s, 1H), 3.73(s, 3H), 2.62(s, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ=161.2, 154.9, 134.3, 133.3, 132.0, 131.3, 131.0, 130.2, 125.0, 122.3, 120.2, 120.1, 111.0, 29.2, 21.8; 19 F NMR (376 MHz, CDCl 3 ): δ=-62.3.
所得产物高分辨质谱数据为:HRMS(ESI)m/z calcd.for C11H10F3N2O[M+H]+:243.0740,found 243.0744。The high-resolution mass spectrum data of the obtained product are: HRMS (ESI) m/z calcd.for C 11 H 10 F 3 N 2 O[M+H] + : 243.0740, found 243.0744.
实施例6Example 6
在25℃下,在10mL反应管中,依次加入7-三氟甲基-1-甲基喹喔啉-2(1H)-酮1f(0.2mmol),二乙酸碘苯2a(0.44mmol),Ru(bpy)3Cl2·6H2O(0.002mmol),PEG-200(1mL),混合均匀,然后在12W白色LED灯照射下,搅拌反应8h。用TLC检测至反应完成后,加入环戊基甲醚(2ml×3)萃取,取上层萃取液,50℃下真空浓缩至无溶剂,得到粗产品,然后用体积比为2:1的石油醚和乙酸乙酯混合洗脱剂冲洗,硅胶柱快速柱层析,得到本实例中的6-甲酯-1,3-二甲基喹喔啉-2(1H)-酮产物3fa,为白色固体40.4mg,收率87%。At 25°C, in a 10 mL reaction tube, 7-trifluoromethyl-1-methylquinoxalin-2(1H)-one 1f (0.2 mmol), and iodobenzene diacetate 2a (0.44 mmol) were sequentially added, Ru(bpy) 3 Cl 2 ·6H 2 O (0.002 mmol), PEG-200 (1 mL), mixed uniformly, and then stirred for 8 h under the irradiation of a 12W white LED lamp. After the reaction was detected by TLC, cyclopentyl methyl ether (2ml×3) was added for extraction, and the upper layer extract was taken and concentrated in vacuo to no solvent at 50°C to obtain a crude product, which was then used with petroleum ether in a volume ratio of 2:1. Rinse with ethyl acetate mixed eluent, silica gel column flash column chromatography to obtain 6-methyl-1,3-dimethylquinoxalin-2(1H)-one product 3fa in this example, which is a white solid 40.4 mg, yield 87%.
所得产物核磁图谱数据为:1H NMR(400MHz,CDCl3):δ=8.48(d,J=2.0Hz,1H),8.17(dd,J1=8.8Hz,J2=2.0Hz,1H),7.32(d,J=8.4Hz,1H),3.95(s,3H),3.72(s,3H),2.60(s,3H);13C NMR(100MHz,CDCl3):δ=166.1,159.4,155.1,136.5,132.0,131.3,130.4,125.5,113.6,52.3,29.3,21.6.The nuclear magnetic spectrum data of the obtained product are: 1 H NMR (400 MHz, CDCl 3 ): δ=8.48 (d, J=2.0 Hz, 1H), 8.17 (dd, J 1 =8.8 Hz, J 2 =2.0 Hz, 1H), 7.32 (d, J=8.4 Hz, 1H), 3.95 (s, 3H), 3.72 (s, 3H), 2.60 (s, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ=166.1, 159.4, 155.1 ,136.5,132.0,131.3,130.4,125.5,113.6,52.3,29.3,21.6.
所得产物高分辨质谱数据为:HRMS(ESI)m/z calcd.for C12H13N2O3[M+H]+:233.0921,found 233.0919.The high-resolution mass spectrometry data of the obtained product are: HRMS (ESI) m/z calcd.for C 12 H 13 N 2 O 3 [M+H] + : 233.0921, found 233.0919.
实施例7Example 7
在25℃下,在10mL反应管中,依次加入1,6,7-三甲基喹喔啉-2(1H)-酮1g(0.2mmol),二乙酸碘苯2a(0.44mmol),Ru(bpy)3Cl2·6H2O(0.002mmol),PEG-200(1mL),混合均匀,然后在12W白色LED灯照射下,搅拌反应8h。用TLC检测至反应完成后,加入环戊基甲醚(2ml×3)萃取,取上层萃取液,50℃下真空浓缩至无溶剂,得到粗产品,然后用体积比为2:1的石油醚和乙酸乙酯混合洗脱剂冲洗,硅胶柱快速柱层析,得到本实例中的1,3,6,7-四甲基喹喔啉-2(1H)-酮产物3ga,为白色固体33.5mg,收率83%。At 25°C, in a 10 mL reaction tube, 1,6,7-trimethylquinoxalin-2(1H)-one 1 g (0.2 mmol), iodobenzene diacetate 2a (0.44 mmol), Ru ( bpy) 3 Cl 2 ·6H 2 O (0.002 mmol), PEG-200 (1 mL), mixed well, and then stirred for 8 h under the irradiation of a 12W white LED lamp. After the reaction was detected by TLC, cyclopentyl methyl ether (2ml×3) was added for extraction, and the upper layer extract was taken and concentrated in vacuo to no solvent at 50°C to obtain a crude product, which was then used with petroleum ether in a volume ratio of 2:1. Rinse with ethyl acetate mixed eluent, and perform flash column chromatography on silica gel to obtain the 1,3,6,7-tetramethylquinoxalin-2(1H)-one product 3ga in this example, which is a white solid 33.5 mg, the yield is 83%.
所得产物核磁图谱数据为:1H NMR(400MHz,CDCl3):δ=7.54(s,1H),7.04(s,1H),3.67(s,3H),2.56(s,3H),2.40(s,3H),2.33(s,3H);13C NMR(100MHz,CDCl3):δ=157.0,155.3,139.2,132.4,131.2,131.0,129.5,114.2,28.9,21.5,20.5,19.2。The nuclear magnetic spectrum data of the obtained product are: 1 H NMR (400MHz, CDCl 3 ): δ=7.54(s, 1H), 7.04(s, 1H), 3.67(s, 3H), 2.56(s, 3H), 2.40(s , 3H), 2.33(s, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ=157.0, 155.3, 139.2, 132.4, 131.2, 131.0, 129.5, 114.2, 28.9, 21.5, 20.5, 19.2.
所得产物高分辨质谱数据为:HRMS(ESI)m/z calcd.for C12H15N2O[M+H]+:203.1179,found 203.1176。The high-resolution mass spectrum data of the obtained product is: HRMS (ESI) m/z calcd.for C 12 H 15 N 2 O[M+H] + : 203.1179, found 203.1176.
实施例8Example 8
在25℃下,在10mL反应管中,依次加入1-苄基喹喔啉-2(1H)-酮1h(0.2mmol),二乙酸碘苯2a(0.44mmol),Ru(bpy)3Cl2·6H2O(0.002mmol),PEG-200(1mL),混合均匀,然后在12W白色LED灯照射下,搅拌反应6h。用TLC检测至反应完成后,加入环戊基甲醚(2ml×3)萃取,取上层萃取液,50℃下真空浓缩至无溶剂,得到粗产品,然后用体积比为2:1的石油醚和乙酸乙酯混合洗脱剂冲洗,硅胶柱快速柱层析,得到本实例中的3-甲基-1-苄基喹喔啉-2(1H)-酮产物3ha,为白色固体43.5mg,收率87%。In a 10 mL reaction tube at 25°C, 1-benzylquinoxalin-2(1H)-one 1h (0.2 mmol), iodobenzene diacetate 2a (0.44 mmol), Ru(bpy) 3 Cl 2 were sequentially added to a 10 mL reaction tube · 6H 2 O (0.002 mmol), PEG-200 (1 mL), mixed well, and then under the irradiation of a 12W white LED lamp, the reaction was stirred for 6 h. After the reaction was detected by TLC, cyclopentyl methyl ether (2ml×3) was added for extraction, and the upper layer extract was taken and concentrated in vacuo to no solvent at 50°C to obtain a crude product, which was then used with petroleum ether in a volume ratio of 2:1. Rinse with ethyl acetate mixed eluent, silica gel column flash column chromatography to obtain 3-methyl-1-benzylquinoxalin-2(1H)-one product 3ha in this example, which is 43.5mg of white solid, Yield 87%.
所得产物核磁图谱数据为:1H NMR(400MHz,CDCl3):δ=7.82(dd,J1=7.6Hz,J2=1.6Hz,1H),7.42–7.38(m,1H),7.34–7.27(m,4H),7.25–7.23(m,3H),5.50(s,2H),2.66(s,3H);13C NMR(100MHz,CDCl3):δ=158.5,155.3,135.2,132.9,132.6,129.6,129.6,128.9,127.7,126.9,123.7,114.4,45.9,21.7.The nuclear magnetic spectrum data of the obtained product are: 1 H NMR (400 MHz, CDCl 3 ): δ=7.82 (dd, J 1 =7.6 Hz, J 2 =1.6 Hz, 1H), 7.42-7.38 (m, 1H), 7.34-7.27 (m, 4H), 7.25-7.23 (m, 3H), 5.50 (s, 2H), 2.66 (s, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ=158.5, 155.3, 135.2, 132.9, 132.6 ,129.6,129.6,128.9,127.7,126.9,123.7,114.4,45.9,21.7.
实施例9Example 9
在25℃下,在10mL反应管中,依次加入1-炔丙基喹喔啉-2(1H)-酮1i(0.2mmol),二乙酸碘苯2a(0.44mmol),Ru(bpy)3Cl2·6H2O(0.002mmol),PEG-200(1mL),混合均匀,然后在12W白色LED灯照射下,搅拌反应7h。用TLC检测至反应完成后,加入环戊基甲醚(2ml×3)萃取,取上层萃取液,50℃下真空浓缩至无溶剂,得到粗产品,然后用体积比为2:1的石油醚和乙酸乙酯混合洗脱剂冲洗,硅胶柱快速柱层析,得到本实例中的3-甲基-1-炔丙基喹喔啉-2(1H)-酮产物3ia,为白色固体43.5mg,收率95%。In a 10 mL reaction tube at 25°C, 1-propargylquinoxalin-2(1H)-one 1i (0.2 mmol), iodobenzene diacetate 2a (0.44 mmol), and Ru(bpy) 3 Cl were sequentially added to a 10 mL reaction tube. 2 · 6H 2 O (0.002 mmol), PEG-200 (1 mL), mixed well, and then under the irradiation of a 12W white LED lamp, the reaction was stirred for 7 h. After the reaction was detected by TLC, cyclopentyl methyl ether (2ml×3) was added for extraction, and the upper layer extract was taken and concentrated in vacuo to no solvent at 50°C to obtain a crude product, which was then used with petroleum ether in a volume ratio of 2:1. Rinse with ethyl acetate mixed eluent, silica gel column flash column chromatography to obtain 3-methyl-1-propargylquinoxalin-2(1H)-one product 3ia in this example, as white solid 43.5mg , the yield is 95%.
所得产物核磁图谱数据为:1H NMR(400MHz,CDCl3):δ=7.82(dd,J1=8.0Hz,J2=1.6Hz,1H),7.58–7.54(m,1H),7.46–7.44(m,1H),7.38–7.34(m,1H),5.05(d,J=2.8Hz,2H),2.60(s,3H),2.29(t,J=2.4Hz,1H);13C NMR(100MHz,CDCl3):δ=158.3,154.2,132.8,131.7,129.7,129.6,124.0,114.1,76.8,73.2,31.5,21.5。The nuclear magnetic spectrum data of the obtained product are: 1 H NMR (400 MHz, CDCl 3 ): δ=7.82 (dd, J 1 =8.0 Hz, J 2 =1.6 Hz, 1H), 7.58-7.54 (m, 1H), 7.46-7.44 (m, 1H), 7.38–7.34 (m, 1H), 5.05 (d, J=2.8Hz, 2H), 2.60 (s, 3H), 2.29 (t, J=2.4Hz, 1H); 13 C NMR ( 100MHz, CDCl 3 ): δ=158.3, 154.2, 132.8, 131.7, 129.7, 129.6, 124.0, 114.1, 76.8, 73.2, 31.5, 21.5.
所得产物高分辨质谱数据为:HRMS(ESI)m/z calcd.for C12H11N2O[M+H]+:199.0866,found 199.0862。The high-resolution mass spectral data of the obtained product are: HRMS (ESI) m/z calcd.for C 12 H 11 N 2 O[M+H] + : 199.0866, found 199.0862.
实施例10Example 10
在25℃下,在10mL反应管中,依次加入2-(2-氧代喹喔啉-1(2H)-基)乙酸乙酯1j(0.2mmol),二乙酸碘苯2a(0.44mmol),Ru(bpy)3Cl2·6H2O(0.002mmol),PEG-200(1mL),混合均匀,然后在12W白色LED灯照射下,搅拌反应8h。用TLC检测至反应完成后,加入环戊基甲醚(2ml×3)萃取,取上层萃取液,50℃下真空浓缩至无溶剂,得到粗产品,然后用体积比为2:1的石油醚和乙酸乙酯混合洗脱剂冲洗,硅胶柱快速柱层析,得到本实例中的3-甲基-2-(2-氧代喹喔啉-1(2H)-基)乙酸乙酯产物3ja,为白色固体39.8mg,收率81%。At 25°C, in a 10 mL reaction tube, sequentially added 2-(2-oxoquinoxalin-1(2H)-yl)ethyl acetate 1j (0.2 mmol), and iodobenzene diacetate 2a (0.44 mmol), Ru(bpy) 3 Cl 2 ·6H 2 O (0.002 mmol), PEG-200 (1 mL), mixed uniformly, and then stirred for 8 h under the irradiation of a 12W white LED lamp. After the reaction was detected by TLC, cyclopentyl methyl ether (2ml×3) was added for extraction, and the upper layer extract was taken and concentrated in vacuo to no solvent at 50°C to obtain a crude product, which was then used with petroleum ether with a volume ratio of 2:1. Rinse with ethyl acetate mixed eluent, silica gel column flash column chromatography to obtain 3-methyl-2-(2-oxoquinoxalin-1(2H)-yl) ethyl acetate product 3ja in this example , as a white solid 39.8 mg, the yield is 81%.
所得产物核磁图谱数据为:1H NMR(400MHz,CDCl3):δ=7.83(dd,J1=8.0Hz,J2=1.6Hz,1H),7.51–7.47(m,1H),7.36–7.32(m,1H),7.06(dd,J1=8.4Hz,J2=0.8Hz,1H),5.02(s,2H),4.28–4.22(m,2H),2.61(s,3H),1.27(t,J=7.2Hz,3H);13C NMR(100MHz,CDCl3):δ=167.1,158.2,154.8,132.7,132.4,129.8,129.7,123.9,113.0,62.1,43.5,21.5,14.1The nuclear magnetic spectrum data of the obtained product are: 1 H NMR (400 MHz, CDCl 3 ): δ=7.83 (dd, J 1 =8.0 Hz, J 2 =1.6 Hz, 1H), 7.51-7.47 (m, 1H), 7.36-7.32 (m, 1H), 7.06(dd, J 1 =8.4Hz, J 2 =0.8Hz, 1H), 5.02(s, 2H), 4.28–4.22(m, 2H), 2.61(s, 3H), 1.27( t, J=7.2 Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ=167.1, 158.2, 154.8, 132.7, 132.4, 129.8, 129.7, 123.9, 113.0, 62.1, 43.5, 21.5, 14.1
所得产物高分辨质谱数据为:HRMS(ESI)m/z calcd.for C13H15N2O3[M+H]+:247.1077,found 247.1068.The high-resolution mass spectral data of the obtained product are: HRMS (ESI) m/z calcd.for C 13 H 15 N 2 O 3 [M+H] + : 247.1077, found 247.1068.
实施例11Example 11
在25℃下,在10mL反应管中,依次加入1-苯基喹喔啉-2(1H)-酮1k(0.2mmol),二乙酸碘苯2a(0.44mmol),Ru(bpy)3Cl2·6H2O(0.002mmol),PEG-200(1mL),混合均匀,然后在12W白色LED灯照射下,搅拌反应6h。用TLC检测至反应完成后,加入环戊基甲醚(2ml×3)萃取,取上层萃取液,50℃下真空浓缩至无溶剂,得到粗产品,然后用体积比为2:1的石油醚和乙酸乙酯混合洗脱剂冲洗,硅胶柱快速柱层析,得到本实例中的3-甲基-1-苯基喹喔啉-2(1H)-酮产物3ka,为白色固体42.5mg,收率90%。At 25°C, in a 10 mL reaction tube, sequentially add 1-phenylquinoxalin-2(1H)-one 1k (0.2 mmol), iodobenzene diacetate 2a (0.44 mmol), Ru(bpy) 3 Cl 2 · 6H 2 O (0.002 mmol), PEG-200 (1 mL), mixed well, and then under the irradiation of a 12W white LED lamp, the reaction was stirred for 6 h. After the reaction was detected by TLC, cyclopentyl methyl ether (2ml×3) was added for extraction, and the upper layer extract was taken and concentrated in vacuo to no solvent at 50°C to obtain a crude product, which was then used with petroleum ether in a volume ratio of 2:1. Rinse with ethyl acetate mixed eluent, silica gel column flash column chromatography, obtain 3-methyl-1-phenylquinoxalin-2(1H)-one product 3ka in this example, it is white solid 42.5mg, Yield 90%.
所得产物核磁图谱数据为:1H NMR(400MHz,CDCl3):δ=7.86–7.83(m,1H),7.63–7.53(m,3H),7.33–7.28(m,4H),6.67–6.65(m,1H),2.64(s,3H);13CNMR(100MHz,CDCl3):δ=159.2,154.9,135.8,134.1,132.5,130.3,129.4,129.2,129.0,128.2,123.8,115.4,21.4.The nuclear magnetic spectrum data of the obtained product are: 1 H NMR (400MHz, CDCl 3 ): δ=7.86-7.83(m, 1H), 7.63-7.53(m, 3H), 7.33-7.28(m, 4H), 6.67-6.65( m, 1H), 2.64 (s, 3H); 13 CNMR (100 MHz, CDCl 3 ): δ=159.2, 154.9, 135.8, 134.1, 132.5, 130.3, 129.4, 129.2, 129.0, 128.2, 123.8, 115.4, 21.4.
实施例12Example 12
在25℃下,在10mL反应管中,依次加入1-烯丙喹喔啉-2(1H)-酮1l(0.2mmol),二乙酸碘苯2a(0.44mmol),Ru(bpy)3Cl2·6H2O(0.002mmol),PEG-200(1mL),混合均匀,然后在12W白光LED灯照射下,搅拌反应8h。用TLC检测至反应完成后,加入环戊基甲醚(2ml×3)萃取,取上层萃取液,50℃下真空浓缩至无溶剂,得到粗产品,然后用体积比为2:1的石油醚和乙酸乙酯混合洗脱剂冲洗,硅胶柱快速柱层析,得到本实例中的3-甲基-1-烯丙基喹喔啉-2(1H)-酮产物3la,为白色固体36.4mg,收率91%。At 25°C, in a 10 mL reaction tube, sequentially add 1-allylquinoxalin-2(1H)-one 11 (0.2 mmol), iodobenzene diacetate 2a (0.44 mmol), Ru(bpy) 3 Cl 2 · 6H 2 O (0.002 mmol), PEG-200 (1 mL), mixed well, and then stirred for 8 h under the irradiation of a 12W white LED lamp. After the reaction was detected by TLC, cyclopentyl methyl ether (2ml×3) was added for extraction, and the upper layer extract was taken and concentrated in vacuo to no solvent at 50°C to obtain a crude product, which was then used with petroleum ether in a volume ratio of 2:1. Rinse with ethyl acetate mixed eluent, silica gel column flash column chromatography to obtain 3-methyl-1-allylquinoxalin-2(1H)-one product 3la in this example, which is 36.4 mg of white solid , the yield is 91%.
所得产物核磁图谱数据为:1H NMR(400MHz,CDCl3):δ=7.81(d,J=8.0Hz,1H),7.48(t,J=7.6Hz,1H),7.34–7.28(m,2H),5.98–5.88(m,1H),5.26(d,J=12.0Hz,1H),5.16(d,J=16.8Hz,1H),4.90(d,J=4.8Hz,2H),2.61(s,3H);13CNMR(100MHz,CDCl3):δ=158.4,154.7,132.8,132.4,130.6,129.5,129.5,123.6,118.0,114.2,44.5,21.5。The nuclear magnetic spectrum data of the obtained product are: 1 H NMR (400MHz, CDCl 3 ): δ=7.81(d, J=8.0Hz, 1H), 7.48(t, J=7.6Hz, 1H), 7.34-7.28(m, 2H) ), 5.98–5.88(m, 1H), 5.26(d, J=12.0Hz, 1H), 5.16(d, J=16.8Hz, 1H), 4.90(d, J=4.8Hz, 2H), 2.61(s , 3H); 13 CNMR (100 MHz, CDCl 3 ): δ=158.4, 154.7, 132.8, 132.4, 130.6, 129.5, 129.5, 123.6, 118.0, 114.2, 44.5, 21.5.
所得产物高分辨质谱数据为:HRMS(ESI)m/z calcd.for C12H13N2O[M+H]+:201.1022,found 201.1019。The high-resolution mass spectrum data of the obtained product is: HRMS (ESI) m/z calcd.for C 12 H 13 N 2 O[M+H] + : 201.1022, found 201.1019.
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