CN109988117B - Preparation method of 3-methylquinoxaline-2 (1H) -ketone derivatives - Google Patents
Preparation method of 3-methylquinoxaline-2 (1H) -ketone derivatives Download PDFInfo
- Publication number
- 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
- Authority
- CN
- China
- Prior art keywords
- alkyl
- reaction
- product
- photocatalyst
- visible light
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 5
- 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 20
- 239000011941 photocatalyst Substances 0.000 claims abstract description 17
- 238000006555 catalytic reaction Methods 0.000 claims abstract description 6
- 238000000034 method Methods 0.000 claims abstract description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 23
- 239000000460 chlorine Substances 0.000 claims description 19
- 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
- 125000002252 acyl group Chemical group 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 7
- 150000002367 halogens Chemical group 0.000 claims description 7
- BMIMNRPAEPIYDN-UHFFFAOYSA-N 3-methyl-2-quinoxalinol Chemical class C1=CC=C2N=C(O)C(C)=NC2=C1 BMIMNRPAEPIYDN-UHFFFAOYSA-N 0.000 claims description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 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 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
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-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
- 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 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
- 239000000049 pigment Substances 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
- 238000004519 manufacturing process Methods 0.000 claims 2
- 238000006243 chemical reaction Methods 0.000 abstract description 42
- 238000005286 illumination Methods 0.000 abstract description 3
- 238000001308 synthesis method Methods 0.000 abstract description 3
- 125000000524 functional group Chemical group 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 230000002349 favourable effect Effects 0.000 abstract 2
- 238000009776 industrial production Methods 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 52
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 41
- 239000000047 product Substances 0.000 description 35
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
- 239000012043 crude product Substances 0.000 description 23
- 239000002904 solvent Substances 0.000 description 19
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- 239000003480 eluent Substances 0.000 description 13
- 238000000605 extraction Methods 0.000 description 13
- 238000003818 flash chromatography 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
- 239000000741 silica gel Substances 0.000 description 13
- 229910002027 silica gel Inorganic materials 0.000 description 13
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 12
- 238000005160 1H NMR spectroscopy Methods 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- 238000001228 spectrum Methods 0.000 description 12
- 238000001819 mass spectrum Methods 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 229910052799 carbon Inorganic materials 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 238000004293 19F NMR spectroscopy Methods 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
- 230000003197 catalytic effect Effects 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
- 238000001514 detection method Methods 0.000 description 2
- 230000000694 effects Effects 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
- 239000002184 metal Substances 0.000 description 2
- 238000007069 methylation reaction Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- FFRYUAVNPBUEIC-UHFFFAOYSA-N quinoxalin-2-ol Chemical class C1=CC=CC2=NC(O)=CN=C21 FFRYUAVNPBUEIC-UHFFFAOYSA-N 0.000 description 2
- 238000003786 synthesis reaction Methods 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
- 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 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
- 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
- 238000006254 arylation reaction Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- NFWMSGZOFCQKCT-UHFFFAOYSA-N ethyl 2-(2-oxoquinoxalin-1-yl)acetate Chemical compound C1=CC=C2N=CC(=O)N(CC(=O)OCC)C2=C1 NFWMSGZOFCQKCT-UHFFFAOYSA-N 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
- 239000012634 fragment Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- ALHUXMDEZNLFTA-UHFFFAOYSA-N methyl-quinoxaline Natural products C1=CC=CC2=NC(C)=CN=C21 ALHUXMDEZNLFTA-UHFFFAOYSA-N 0.000 description 1
- 230000011987 methylation Effects 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
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 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
- 238000007146 photocatalysis Methods 0.000 description 1
- 230000001699 photocatalysis Effects 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000011160 research Methods 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
- 238000003756 stirring Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 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
- 238000005406 washing 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
Abstract
The invention discloses a preparation method of 3-methylquinoxaline-2 (1H) -ketone compounds, which comprises the steps of carrying out visible light catalytic reaction on a quinoxalinone compound and iodobenzene diacetate under the action of a photocatalyst to obtain a 3-methylquinoxalinone compound; compared with the prior art, the synthesis method has the advantages that 1) the used quinoxaline-2 (1H) -ketone derivative is cheap and easy to obtain in raw materials and is favorable for reducing the cost, 2) the reaction can be carried out at room temperature by illumination, the conditions are mild, the product can be obtained in one step, the reaction yield is high, the operation is environment-friendly and is favorable for industrial production, and 3) the method has good applicability to functional groups and can obtain various 3-methyl quinoxalinone compound derivatives.
Description
Technical Field
The invention relates to a synthesis method of quinoxalinone derivatives, in particular to a method for preparing 3-methylquinoxalin-2 (1H) -one by one step through photocatalysis under the action of a photocatalyst by taking quinoxaline-2 (1H) -one compounds and iodobenzene diacetate as starting raw materials, belonging to the technical field of organic synthesis.
Background
Methyl is the smallest alkyl fragment, which is found in most drug molecules, and introduction of methyl groups into the molecule improves drug solubility, selectivity and metabolic activity of the drug molecule. The introduction of methyl at the ortho position of the metabolic site generates steric hindrance, can prolong the half-life of the medicine, such as simvastatin, and pharmaceutical chemists can also generate new metabolic sites by introducing the methyl if the half-life of the medicine is too long, so as to shorten the half-life of the medicine, such as etoricoxib.
Quinoxaline-2 (1H) -ketone is an important nitrogen heterocyclic derivative, and the application of the derivative in natural products, pharmacy and material science is very common, wherein 3-methylquinoxaline-2 (1H) -ketone derivatives attract the interest of a large number of researchers in organic chemistry because of the characteristic that the derivatives can regulate the bioactivity of the quinoxaline. For example, compound a is a c-met kinase inhibitor (bioorg.med.chem.2015,23,6560), and the introduction of methyl groups significantly improves the pharmaceutical activity of the molecule.
At present, researches on arylation, acylation, phosphorylation, ammoniation, trifluoromethylation and the like of C3 site of quinoxaline-2 (1H) -ketone are reported, but no related report is found on direct methylation of C3 site of quinoxaline-2 (1H) -ketone compound.
Disclosure of Invention
Aiming at the technical blank existing in the C3 alkylation reaction of quinoxaline-2 (1H) -ketone in the prior art, the invention aims to provide a synthesis method for realizing 3-methylquinoxaline-2 (1H) -ketone and derivatives thereof under mild conditions by using a photocatalytic reaction, the method avoids using a metal catalyst polluting the environment by using the photocatalyst, and simultaneously, the reaction is carried out under the conditions of normal temperature illumination, constant temperature and constant temperature, high temperature and other complicated operations are avoided, the reaction cost and energy consumption can be reduced, the reaction efficiency is improved, and the purpose of greening chemistry is achieved.
In order to realize the technical purpose, the invention provides a preparation method of 3-methylquinoxaline-2 (1H) -ketone compounds, wherein the quinoxaline compound with the structure of formula 1, iodobenzene diacetate with the structure of formula 2 and a photocatalyst are subjected to visible light catalytic reaction to obtain the 3-methylquinoxaline compound with the structure of formula 3;
wherein,
R1is hydrogen, alkyl or aralkyl;
R2and R3Independently selected from hydrogen, alkyl, alkoxy, nitro, amino, acyl, halogen substituents, hydroxy, cyano or trifluoromethyl.
The compounds of formula 1, formula 2 and formula 3 of the present invention. R1Is a group substituted on the nitrogen atom, which may be selected as a hydrogen atom, or may be other groups substituted for a hydrogen atom, such as an alkyl group or an aralkyl group substituted for a hydrogen atom. Alkyl is C1~C8The alkyl group of (A) may be a straight-chain alkyl group or a branched alkyl group, or a cyclic alkyl group, such as methyl, ethyl, butylIsopropyl, cyclohexyl, and the like. Aralkyl is essentially an alkyl chain substituted with an aryl group, the length of the alkyl chain being C1~C8By substitution of aryl groups, such as phenyl, naphthyl or substituted phenyl, at any carbon atom of the alkyl chain, substituted phenyl being phenyl rings containing some conventional substituents, such as C1~C5Alkyl of (C)1~C5Alkoxy, halo substituents, and the like, with aralkyl groups such as benzyl, phenylethyl, and the like being most common. R2And R3Is a substituent group contained on the benzene ring of the quinoxalinone compound, R2And R3The influence on the C3 alkylation reaction of the quinoxalinone compound is relatively small, the substituted position can be any position which can be substituted on a benzene ring, and the selection range is wide, such as hydrogen, alkyl, alkoxy, nitro, amino, acyl, halogen substituent, hydroxyl, cyano or trifluoromethyl, and the like, when R is2Or R3When alkyl is selected, the alkyl is C1~C8The alkyl group of (b) may be a straight-chain alkyl group or a branched-chain alkyl group, or a cyclic alkyl group, specifically, such as methyl, ethyl, butyl, isopropyl, cyclohexyl, etc.; r2Or R3When alkoxy is selected, alkoxy is C1~C8Alkoxy groups of (a), such as methoxy, ethoxy, isobutoxy, etc.; r2Or R3When acyl is selected, the acyl is formyl, acetyl or propionyl; r2Or R3When a halogen substituent is selected, the halogen substituent is fluorine, chlorine, bromine or iodine.
In a preferred scheme, the molar ratio of the quinoxaline-2-ketone derivative to iodobenzene diacetate is as follows: 1:1 to 1: 20. More preferably 1:1 to 1: 10.
In a preferable scheme, the molar ratio of the quinoxaline-2-ketone derivative to the photocatalyst is 1: 0.01-1: 0.05.
Preferably, the photocatalyst comprises Ru (bpy)3Cl2Eosin B (C)20H6Br2N2Na2O9) Eosin (eosin Y, C)20H6Br4Na3O5) Alcohol soluble eosin, rhodamine B, edibleAt least one pigment red. The most preferred photocatalyst is Ru (bpy)3Cl2。
In a preferred embodiment, the visible light catalytic reaction conditions are as follows: and reacting for 6-12 hours at room temperature under the irradiation of visible light.
Preferably, the visible light source is an LED white light source, a blue light source or a green light source with power of 3W-24W. The preferred visible light source is an LED white light source with a power of 12W.
In a preferred embodiment, the photocatalytic reaction is performed in DMSO, DMF, CHCl3、CH3OH, PEG-200 and PEG-400. A more preferred reaction medium is PEG-200.
The synthetic route of the 3-methylquinoline-2 (1H) -ketone compound is as follows:
the synthetic reaction mechanism of the 3-methylquinoxaline-2 (1H) -ketone compound is as follows: the photocatalyst is activated by light to release electrons, the released electrons are captured by iodobenzene diacetate, the iodobenzene diacetate capturing the electrons releases methyl radicals through cracking, the methyl radicals attack the 3-position carbon of the quinoxalinone compound to form an intermediate A, the intermediate A is abstracted back to the electrons by the photocatalyst to be converted into an unstable intermediate B, and the intermediate B undergoes intramolecular recombination and releases hydrogen protons to obtain the target compound.
Compared with the prior art, the technical scheme of the invention has the beneficial technical effects that:
the invention avoids using metal catalyst which pollutes the environment by using the green and environment-friendly photocatalyst.
The quinoxalinone compound C3 has high methylation reaction efficiency and can obtain high selectivity yield.
The method has mild reaction conditions, can perform reaction under the conditions of normal temperature illumination and isothermy, avoids high temperature and other complicated operations, and reduces the reaction cost and energy consumption.
The invention has good applicability to functional groups, can obtain various 3-methylquinoxalinone compound derivatives, and provides a brand new path for synthesizing the quinoxalinone compound derivatives.
Detailed Description
The following examples are intended to further illustrate the present disclosure, but not to limit the scope of the claims.
Condition optimization experiment:
the specific reaction conditions were as follows: the compound 1a (0.2mmol), iodobenzene diacetate 2a (0.44mmol), a photocatalyst and a solvent (1mL) were added in this order to a 10mL reaction tube at 25 ℃ and mixed well, followed by stirring and reaction for 8h under the irradiation of a 12w white LED lamp. Detecting by TLC until the reaction is finished, adding cyclopentyl methyl ether (2ml multiplied by 3) for extraction, taking the upper layer of extract, concentrating the extract in vacuum at 50 ℃ until no solvent exists to obtain a crude product, then washing the crude product by using a mixed eluent of petroleum ether and ethyl acetate with the volume ratio of 2:1, and performing silica gel column flash column chromatography to obtain a product 3 aa.
In order to obtain the 3-methyl-2 (1H) -quinoxalinone compound with high yield, the following control experiment groups 1-13 are carried out according to the reaction conditions, some condition factors influencing the reaction are investigated, the condition factors mainly comprise the type and the solvent of the photocatalyst, and the specific optimization process is shown in the following table:
as can be seen from the above table, of all the photocatalysts used in the experiments, Ru (bpy)3Cl2The synthesis of 3-methyl-2 (1H) -quinoxalinone compounds can be realized by the photocatalysts such as eosin B, water-soluble eosin and the like, but Ru (bpy)3Cl2Has the best catalytic effect. And is catalyzed byThe dosage of the catalyst is about 1 percent, so that a good catalytic effect can be achieved. For the choice of solvent, the most preferred solvent is PEG-200; secondly, DMF and DMSO are good solvents for reaction, and acetonitrile, tetrahydrofuran and dichloroethane as solvents hardly obtain target products.
The following specific embodiments 1 to 12 are all reacted under optimized conditions, and the influence of different substituent groups on the reaction is examined.
Example 1
1-Methylquinoxalin-2 (1H) -one 1a (0.2mmol), iodobenzene diacetate 2a (0.44mmol), Ru (bpy) were added sequentially in a 10mL reaction tube at 25 deg.C3Cl2·6H2O (0.002mmol), PEG-200(1mL) are mixed uniformly, then stirred and reacted for 8H under the irradiation of a 12w white LED lamp, after the reaction is detected to be finished by TLC, cyclopentyl methyl ether (2mL × 3) is added for extraction, the upper layer of extract is taken and concentrated in vacuum at 50 ℃ until no solvent is available, a crude product is obtained, then the crude product is washed by mixed eluent of petroleum ether and ethyl acetate with the volume ratio of 2:1, and the silica gel column flash column chromatography is carried out, so that the product 3aa of the 1, 3-dimethyl quinoxaline-2 (1H) -one in the example is obtained, the white solid is 32.8mg, and the yield is 91%.
The nuclear magnetic spectrum data of the obtained product are as follows:1H NMR(400MHz,CDCl3):=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):=158.4,155.2,133.2,132.6,129.6,129.4,123.6,113.6,29.0,21.6.
example 2
At 25 ℃, in a 10mL reaction tube, 6-bromo-1-methylquinoxaline-2 (1H) -one 1b (0.2mmol), iodobenzene diacetate 2a (0.44mmol), Ru (bpy)3Cl2·6H2O (0.002mmol), PEG-200(1mL), mixed well and then irradiated in a 12W white LED lampThen, the reaction is stirred for 8H, TLC is used for detection until the reaction is completed, cyclopentyl methyl ether (2ml × 3) is added for extraction, the upper layer of extract liquid is taken and concentrated in vacuum at 50 ℃ until no solvent is obtained, a crude product is obtained, then the crude product is washed by mixed eluent of petroleum ether and ethyl acetate with the volume ratio of 2:1, and silica gel column flash column chromatography is carried out, so that the 6-bromo-1, 3-dimethyl quinoxalin-2 (1H) -one product 3ba in the example is obtained, and is 42.8mg of white solid, and the yield is 85%.
The nuclear magnetic spectrum data of the obtained product are as follows:1H NMR(400MHz,CDCl3):=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):=159.8,154.8,133.5,132.4,132.3,131.9,116.1,115.0,29.2,21.7。
the obtained high-resolution mass spectrum data of the product are as follows: for r C HRMS calc10H10BrN2O[M+H]+:252.9971,found 252.9968。
Example 3
At 25 ℃, in a 10mL reaction tube, 7-fluoro-1-methylquinoxaline-2 (1H) -one 1c (0.2mmol), iodobenzene diacetate 2a (0.44mmol), Ru (bpy)3Cl2·6H2O (0.002mmol), PEG-200(1mL) are mixed uniformly, then stirred and reacted for 6H under the irradiation of a 12W white LED lamp, after the reaction is detected to be finished by TLC, cyclopentyl methyl ether (2mL × 3) is added for extraction, the upper layer of extract is taken and concentrated in vacuum at 50 ℃ until no solvent is available, a crude product is obtained, then the crude product is washed by mixed eluent of petroleum ether and ethyl acetate with the volume ratio of 2:1, and the silica gel column is subjected to flash column chromatography, so that the product 3ca of the 7-fluoro-1, 3-dimethyl quinoxaline-2 (1H) -one in the example is obtained, the white solid is 35.3mg, and the yield is 92%.
The nuclear magnetic spectrum data of the obtained product are as follows:1H NMR(400MHz,CDCl3):=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):=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):=-108.3.
the obtained high-resolution mass spectrum data of the product are as follows: HRMS (ESI) m/z calcd.for C10H10FN2O[M+H]+:193.0772,found 193.0770。
Example 4
At 25 ℃, in a 10mL reaction tube, 6-nitro-1-methylquinoxaline-2 (1H) -one 1d (0.2mmol), iodobenzene diacetate 2a (0.44mmol), Ru (bpy)3Cl2·6H2O (0.002mmol), PEG-200(1mL) were mixed well, and then stirred to react for 8H under 12W white LED lamp irradiation, after TLC detection till the reaction was completed, cyclopentyl methyl ether (2mL × 3) was added for extraction, the upper extract was taken and concentrated in vacuo at 50 ℃ until no solvent was present to give a crude product, which was then washed with a mixed eluent of petroleum ether and ethyl acetate at a volume ratio of 2:1 and flash column chromatography on silica gel column to give 6-nitro-1, 3-dimethylquinoxalin-2 (1H) -one product 3da in this example as a yellow solid 36.8mg, yield 84%.
The nuclear magnetic spectrum data of the obtained product are as follows:1H NMR(400MHz,CDCl3):=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):=161.2,154.8,143.4,137.9,131.8,125.2,124.2,114.2,29.6,21.7。
the obtained high-resolution mass spectrum data of the product are as follows: HRMS (ESI) m/z calcd.for C10H10N3O3[M+H]+:220.0717,found 220.0713。
Example 5
7-Tris-chloride was sequentially added to a 10mL reaction tube at 25 deg.CFluoromethyl-1-methylquinoxalin-2 (1H) -one 1e (0.2mmol), iodobenzene diacetate 2a (0.44mmol), Ru (bpy)3Cl2·6H2O (0.002mmol), PEG-200(1mL) are mixed uniformly, then the mixture is stirred and reacted for 7H under the irradiation of a 12W white LED lamp, after the reaction is detected to be finished by TLC, cyclopentyl methyl ether (2mL × 3) is added for extraction, the upper layer of extract liquor is taken and concentrated in vacuum at 50 ℃ until no solvent is available, a crude product is obtained, then the crude product is washed by mixed eluent of petroleum ether and ethyl acetate with the volume ratio of 2:1, and the silica gel column flash column chromatography is carried out, so that the product 3ea of the 7-trifluoromethyl-1, 3-dimethyl quinoxaline-2 (1H) -ketone in the example is obtained, the white solid is 43.6mg, and the yield is 90%.
The nuclear magnetic spectrum data of the obtained product are as follows:1H NMR(400MHz,CDCl3):=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):=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):=-62.3。
the obtained high-resolution mass spectrum data of the product are as follows: HRMS (ESI) m/z calcd.for C11H10F3N2O[M+H]+:243.0740,found 243.0744。
Example 6
7-trifluoromethyl-1-methylquinoxalin-2 (1H) -one 1f (0.2mmol), iodobenzene diacetate 2a (0.44mmol), Ru (bpy) were added sequentially at 25 ℃ in a 10mL reaction tube3Cl2·6H2O (0.002mmol), PEG-200(1mL) were mixed well, and then reacted for 8H under 12W white LED lamp irradiation, TLC was used to detect that the reaction was completed, cyclopentyl methyl ether (2mL × 3) was added for extraction, the upper layer extract was taken and concentrated in vacuo at 50 ℃ until no solvent was present to give a crude product, which was then washed with a mixed eluent of petroleum ether and ethyl acetate at a volume ratio of 2:1 and flash column chromatography on silica gel column to give 6-methyl ester-1, 3-dimethylquinoxalin-2 (1H) -one product 3fa in this example as a white solid 40.4mg with a yield of 87%.
The nuclear magnetic spectrum data of the obtained product are as follows:1H NMR(400MHz,CDCl3):=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):=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 obtained high-resolution mass spectrum data of the product are as follows: HRMS (ESI) m/z calcd.for C12H13N2O3[M+H]+:233.0921,found 233.0919.
Example 7
1g (0.2mmol) of 1,6, 7-trimethylquinoxalin-2 (1H) -one, iodobenzene diacetate 2a (0.44mmol), Ru (bpy) were added sequentially at 25 ℃ in a 10mL reaction tube3Cl2·6H2O (0.002mmol), PEG-200(1mL) are mixed uniformly, then the mixture is stirred and reacted for 8H under the irradiation of a 12W white LED lamp, after the reaction is detected to be finished by TLC, cyclopentyl methyl ether (2mL × 3) is added for extraction, the upper layer of extract liquor is taken and concentrated in vacuum at 50 ℃ until no solvent is available, a crude product is obtained, then the crude product is washed by mixed eluent of petroleum ether and ethyl acetate with the volume ratio of 2:1, and the silica gel column flash column chromatography is carried out, so that the product 3ga of 1,3,6, 7-tetramethyl quinoxaline-2 (1H) -one in the example is obtained, the white solid is 33.5mg, and the yield is 83%.
The nuclear magnetic spectrum data of the obtained product are as follows:1H NMR(400MHz,CDCl3):=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):=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 obtained high-resolution mass spectrum data of the product are as follows: HRMS (ESI) m/z calcd.for C12H15N2O[M+H]+:203.1179,found 203.1176。
Example 8
1-Benzylquinoxalin-2 (1H) -one 1H (0.2mmol), iodobenzene diacetate 2a (0.44mmol), Ru (bpy) were added sequentially in a 10mL reaction tube at 25 deg.C3Cl2·6H2O (0.002mmol), PEG-200(1mL) are mixed uniformly, then stirred and reacted for 6H under the irradiation of a 12W white LED lamp, after the reaction is detected to be finished by TLC, cyclopentyl methyl ether (2mL × 3) is added for extraction, the upper layer of extract is taken and concentrated in vacuum at 50 ℃ until no solvent is available, a crude product is obtained, then the crude product is washed by mixed eluent of petroleum ether and ethyl acetate with the volume ratio of 2:1, and the silica gel column flash column chromatography is carried out, so that 3-methyl-1-benzyl quinoxaline-2 (1H) -one product 3ha in the example is obtained, the white solid is 43.5mg, and the yield is 87%.
The nuclear magnetic spectrum data of the obtained product are as follows:1H NMR(400MHz,CDCl3):=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):=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.
example 9
1-propargylquinoxalin-2 (1H) -one 1i (0.2mmol), iodobenzene diacetate 2a (0.44mmol), Ru (bpy) were added sequentially at 25 ℃ in a 10mL reaction tube3Cl2·6H2O (0.002mmol), PEG-200(1mL) were mixed well, and then reacted for 7H under 12W white LED lamp irradiation, TLC was used to detect that the reaction was completed, cyclopentyl methyl ether (2mL × 3) was added for extraction, the upper layer extract was taken and concentrated in vacuo at 50 ℃ until no solvent was present to give a crude product, which was then washed with a mixed eluent of petroleum ether and ethyl acetate at a volume ratio of 2:1 and flash column chromatography on silica gel column to give 3-methyl-1-propargyl quinoxalin-2 (1H) -one product 3ia in this example as a white solid 43.5mg, yield 95%.
The nuclear magnetic spectrum data of the obtained product are as follows:1H NMR(400MHz,CDCl3):=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):=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 obtained high-resolution mass spectrum data of the product are as follows: HRMS (ESI) m/z calcd.for C12H11N2O[M+H]+:199.0866,found 199.0862。
Example 10
In a 10mL reaction tube at 25 ℃, ethyl 2- (2-oxoquinoxalin-1 (2H) -yl) acetate 1j (0.2mmol), iodobenzene diacetate 2a (0.44mmol), Ru (bpy)3Cl2·6H2O (0.002mmol), PEG-200(1mL) are mixed uniformly, then the mixture is stirred and reacted for 8H under the irradiation of a 12W white LED lamp, after the reaction is detected to be finished by TLC, cyclopentyl methyl ether (2mL × 3) is added for extraction, the upper layer of extract liquor is taken and concentrated in vacuum at 50 ℃ until no solvent is available, a crude product is obtained, then the crude product is washed by mixed eluent of petroleum ether and ethyl acetate with the volume ratio of 2:1, and the silica gel column flash column chromatography is carried out, so that the 3-methyl-2- (2-oxo-quinoxaline-1 (2H) -yl) ethyl acetate product 3ja in the example is obtained, the white solid is 39.8mg, and the yield is 81%.
The nuclear magnetic spectrum data of the obtained product are as follows:1H NMR(400MHz,CDCl3):=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):=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
the obtained high-resolution mass spectrum data of the product are as follows: HRMS (ESI) m/z calcd.for C13H15N2O3[M+H]+:247.1077,found 247.1068.
Example 11
1-Phenylquinoxalin-2 (1H) -one 1k (0.2mmol), iodobenzene diacetate 2a (0.44mmol), Ru (bpy) were added sequentially at 25 ℃ in a 10mL reaction tube3Cl2·6H2O (0.002mmol), PEG-200(1mL) are mixed uniformly, then stirred and reacted for 6H under the irradiation of a 12W white LED lamp, after the reaction is detected to be finished by TLC, cyclopentyl methyl ether (2mL × 3) is added for extraction, the upper layer of extract is taken and concentrated in vacuum at 50 ℃ until no solvent is available, a crude product is obtained, then the crude product is washed by mixed eluent of petroleum ether and ethyl acetate with the volume ratio of 2:1, and the silica gel column flash column chromatography is carried out, so that the 3-methyl-1-phenylquinoxaline-2 (1H) -one product 3ka in the example is obtained, and is 42.5mg of white solid with the yield of 90 percent.
The nuclear magnetic spectrum data of the obtained product are as follows:1H NMR(400MHz,CDCl3):=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):=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.
example 12
1-allylquinoxalin-2 (1H) -one 1l (0.2mmol), iodobenzene diacetate 2a (0.44mmol), Ru (bpy) were added sequentially at 25 ℃ in a 10mL reaction tube3Cl2·6H2O (0.002mmol), PEG-200(1mL) are mixed uniformly, then stirred and reacted for 8H under the irradiation of a 12W white light LED lamp, after the reaction is detected to be finished by TLC, cyclopentyl methyl ether (2mL × 3) is added for extraction, the upper layer extract is taken and concentrated in vacuum at 50 ℃ until no solvent is available, a crude product is obtained, then the crude product is washed by mixed eluent of petroleum ether and ethyl acetate with the volume ratio of 2:1, and the silica gel column flash column chromatography is carried out, so that the 3-methyl-1-allyl quinoxaline-2 (1H) -one product 3la in the example is obtained, and is 36.4mg of white solid with the yield of 91%.
The nuclear magnetic spectrum data of the obtained product are as follows:1H NMR(400MHz,CDCl3):=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):=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 obtained high-resolution mass spectrum data of the product are as follows: HRMS (ESI) m/z calcd.for C12H13N2O[M+H]+:201.1022,found 201.1019。
Claims (4)
1. A preparation method of 3-methylquinoxaline-2 (1H) -ketone compounds is characterized in that: carrying out visible light catalytic reaction on the quinoxalinone compound with the structure of formula 1 and iodobenzene diacetate with the structure of formula 2 under the action of a photocatalyst to obtain a 3-methyl quinoxalinone compound with the structure of formula 3;
wherein,
R1is hydrogen, alkyl or aralkyl;
R2and R3Independently selected from hydrogen, alkyl, alkoxy, nitro, amino, acyl, halogen substituents, hydroxy, cyano or trifluoromethyl;
R1when selected from alkyl, the alkyl is C1~C8Alkyl groups of (a); r1When selected from aralkyl, the aralkyl is benzyl or phenylethyl;
R2or R3When alkyl is selected, the alkyl is C1~C8Alkyl groups of (a); r2Or R3When alkoxy is selected, alkoxy is C1~C8Alkoxy group of (a); r2Or R3When acyl is selected, the acyl is formyl, acetyl or propionyl; r2Or R3When a halogen substituent is selected, the halogen substituent is fluorine, chlorine, bromine or iodine;
the photocatalyst is Ru (bpy)3Cl2At least one of eosin B, water-soluble eosin, alcohol-soluble eosin, rhodamine B and edible pigment red;
the photocatalytic reaction is carried out in DMSO, DMF, CHCl3、CH3OH, PEG-200 and PEG-400.
2. The process according to claim 1 for preparing 3-methylquinoxalin-2 (1H) -ones, wherein:
the mol ratio of the quinoxaline-2 (1H) -ketone derivative to iodobenzene diacetate is as follows: 1: 1-1: 20;
the molar ratio of the quinoxaline-2 (1H) -ketone derivative to the photocatalyst is 1: 0.01-1: 0.05.
3. The process for preparing 3-methylquinoxalin-2 (1H) -ones according to claim 1 or 2, characterized in that: the visible light catalytic reaction conditions are as follows: and reacting for 6-12 hours at room temperature under the irradiation of visible light.
4. The process for preparing 3-methylquinoxalin-2 (1H) -ones according to claim 3, characterized in that: the visible light catalytic reaction adopts an LED white light source with the power of 3W-24W, a blue light source with the power of 3W-24W or a green light source with the power of 3W-24W.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910429014.8A CN109988117B (en) | 2019-05-22 | 2019-05-22 | Preparation method of 3-methylquinoxaline-2 (1H) -ketone derivatives |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910429014.8A CN109988117B (en) | 2019-05-22 | 2019-05-22 | Preparation method of 3-methylquinoxaline-2 (1H) -ketone derivatives |
Publications (2)
Publication Number | Publication Date |
---|---|
CN109988117A CN109988117A (en) | 2019-07-09 |
CN109988117B true CN109988117B (en) | 2020-09-29 |
Family
ID=67136889
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201910429014.8A Expired - Fee Related CN109988117B (en) | 2019-05-22 | 2019-05-22 | Preparation method of 3-methylquinoxaline-2 (1H) -ketone derivatives |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN109988117B (en) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110437164B (en) * | 2019-08-20 | 2022-03-25 | 浙江工业大学 | Method for synthesizing C-3 alkyl substituted quinoxalinone derivative based on Minisci reaction |
CN110983368B (en) * | 2019-11-06 | 2021-04-09 | 北京工业大学 | Synthesis method of nickel-catalyzed C-3 alkyl substituted quinoxalinone under electrochemical condition |
CN111116497B (en) * | 2019-11-20 | 2021-05-25 | 温州医科大学 | Preparation method of 3-methylquinoxaline-2- (1H) -one derivative |
CN110862347B (en) * | 2019-12-05 | 2022-03-04 | 哈尔滨工业大学 | Preparation method of 2-aryl substituted quinoline nitroxide compound |
CN112028841B (en) * | 2020-08-27 | 2021-12-31 | 湖南科技学院 | Photocatalytic synthesis method of 3-aryl-N-methylquinoxaline-2 (1H) -ketone compound |
CN111892545B (en) * | 2020-08-31 | 2021-11-05 | 怀化学院 | Green synthesis method of 1-methyl-3-alkyl quinoxalinone compound |
CN112321517A (en) * | 2020-11-16 | 2021-02-05 | 杭州师范大学 | 3-aryl-2 (1H) -quinoxalinone and synthetic method thereof |
CN112812069B (en) * | 2021-02-21 | 2022-08-09 | 山东京博生物科技有限公司 | Synthetic method of 3-methyl-3-quinolol |
CN113943257B (en) * | 2021-09-06 | 2024-06-14 | 青岛科技大学 | Synthesis method and application of photocatalytic C-3-alkyl substituted quinoxaline-2 (1H) -ketone compound |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE102004023332A1 (en) * | 2004-05-12 | 2006-01-19 | Bayer Cropscience Gmbh | Quinoxaline-2-one derivatives, crop protection agents containing them, and processes for their preparation and their use |
CN108752325B (en) * | 2018-08-06 | 2021-03-23 | 曲阜师范大学 | Preparation method of 3-oxyalkyl quinoxaline-2 (1H) -ketone compound |
CN109160903B (en) * | 2018-09-28 | 2021-07-16 | 曲阜师范大学 | Photocatalytic preparation method of 3-aminoquinoxaline-2 (1H) -ketone compound |
-
2019
- 2019-05-22 CN CN201910429014.8A patent/CN109988117B/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
CN109988117A (en) | 2019-07-09 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN109988117B (en) | Preparation method of 3-methylquinoxaline-2 (1H) -ketone derivatives | |
CN110117260B (en) | Preparation method of 3-alkyl quinoxaline-2 (1H) -ketone compound | |
EP1027316B1 (en) | Synthesis of aryl ethers, methods and reagents related thereto | |
JP6846906B2 (en) | Synthesis of substituted salicylaldehyde derivatives | |
Masters et al. | The Acetal Concept: Regioselective Access to ortho, ortho-Diphenols via Dibenzo-1, 3-dioxepines. | |
CN110845428A (en) | Photocatalytic preparation method of 3-acyl quinoxalinone compound | |
CN107840819B (en) | Synthesis method of polysubstituted isoindolinone derivative | |
CN109320489A (en) | A kind of color alkyl compound and preparation method thereof | |
CN108059610B (en) | Preparation method of 3-acyl spiro-trienone compound | |
CN110590788B (en) | 2-acyl-9H-pyrrolo [1,2-a]Synthesis method of indole compound | |
CN109651271B (en) | Synthetic method of 3-tert-butyl-N-methylquinoxaline-2 (1H) -ketone compound | |
CN111484436B (en) | Method for introducing isopentene group into C3 position of indole | |
Fumagalli et al. | Pd (II)-mediated cyclodehydrogenation of formyldiarylamines—total synthesis of natural carbazoles clauraila A, clausenal and 6-methoxymurrayanine | |
CN111269228A (en) | Preparation method of indolizine ring-1, 2-diketone and derivative thereof with fluorescence activity | |
CN110627734A (en) | Preparation method of 3-alkoxy substituted quinoxalinone derivative | |
CN114014805B (en) | Preparation method of trifluoromethyl 2, 4-quinoline diketone compound | |
CN111484437A (en) | Method for introducing tertiary isopentenyl group to C3 position of indole | |
CN110698483B (en) | Synthesis of 2-sulfonyl-9H-pyrrolo [1,2-a ] indole compound | |
CN111393437B (en) | Trisubstituted indolizine compound and preparation method thereof | |
CN107954960B (en) | Synthetic method of 1,3-dihydroisobenzofuran compound | |
CN107954872B (en) | Method for synthesizing malonate type compound | |
CN108586457B (en) | indole carbocycle dearomatization synthesis method based on nitrogen atom α hydrogen migration strategy | |
CN105801333B (en) | A kind of preparation method of coronene | |
CN114773229B (en) | 1,6 Diene compound and preparation method and application thereof | |
KR102292794B1 (en) | Preparation method of 2-substituted 1,2,3,4-tetrahydroquinoline compound |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant | ||
CF01 | Termination of patent right due to non-payment of annual fee | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20200929 Termination date: 20210522 |