CN117964553A - Method for selectively synthesizing 2-amido quinoline-N-oxide compound from quinoline-N-oxide compound - Google Patents
Method for selectively synthesizing 2-amido quinoline-N-oxide compound from quinoline-N-oxide compound Download PDFInfo
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- -1 quinoline-N-oxide compound Chemical class 0.000 title claims abstract description 26
- 238000000034 method Methods 0.000 title claims abstract description 20
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 13
- GIIWGCBLYNDKBO-UHFFFAOYSA-N Quinoline 1-oxide Chemical class C1=CC=C2[N+]([O-])=CC=CC2=C1 GIIWGCBLYNDKBO-UHFFFAOYSA-N 0.000 claims abstract description 15
- 238000006243 chemical reaction Methods 0.000 claims abstract description 10
- CQLFBEKRDQMJLZ-UHFFFAOYSA-M silver acetate Chemical compound [Ag+].CC([O-])=O CQLFBEKRDQMJLZ-UHFFFAOYSA-M 0.000 claims abstract description 9
- 229940071536 silver acetate Drugs 0.000 claims abstract description 9
- 239000003054 catalyst Substances 0.000 claims abstract description 8
- QXDOFVVNXBGLKK-UHFFFAOYSA-N 3-Isoxazolidinone Chemical compound OC1=NOCC1 QXDOFVVNXBGLKK-UHFFFAOYSA-N 0.000 claims abstract description 7
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims abstract 2
- 229910052802 copper Inorganic materials 0.000 claims abstract 2
- 239000010949 copper Substances 0.000 claims abstract 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 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
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 125000000217 alkyl group Chemical group 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
- 239000000460 chlorine Substances 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 125000001207 fluorophenyl group Chemical group 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract description 10
- 229910052757 nitrogen Inorganic materials 0.000 abstract description 5
- 239000000758 substrate Substances 0.000 abstract description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 abstract 2
- 229910052741 iridium Inorganic materials 0.000 abstract 1
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 abstract 1
- 239000003446 ligand Substances 0.000 abstract 1
- 229910000510 noble metal Inorganic materials 0.000 abstract 1
- 229910052763 palladium Inorganic materials 0.000 abstract 1
- 229910052703 rhodium Inorganic materials 0.000 abstract 1
- 239000010948 rhodium Substances 0.000 abstract 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 abstract 1
- 238000006467 substitution reaction Methods 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 44
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 13
- 238000005160 1H NMR spectroscopy Methods 0.000 description 13
- 238000001228 spectrum Methods 0.000 description 13
- 230000015572 biosynthetic process Effects 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
- VDQCQTULYAZNNT-UHFFFAOYSA-N 4-phenyl-1,2-oxazol-3-one Chemical compound O=C1NOC=C1C1=CC=CC=C1 VDQCQTULYAZNNT-UHFFFAOYSA-N 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 238000001308 synthesis method Methods 0.000 description 5
- 230000004913 activation Effects 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 230000002035 prolonged effect Effects 0.000 description 3
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 2
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 2
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 2
- QGLUGLQOMMPQQX-UHFFFAOYSA-N C1=CC=CC2=[N+]([O-])C(N)=CC=C21 Chemical class C1=CC=CC2=[N+]([O-])C(N)=CC=C21 QGLUGLQOMMPQQX-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 229940125904 compound 1 Drugs 0.000 description 2
- 229940125797 compound 12 Drugs 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 150000003248 quinolines Chemical class 0.000 description 2
- 150000003335 secondary amines Chemical class 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- UVNPEUJXKZFWSJ-LMTQTHQJSA-N (R)-N-[(4S)-8-[6-amino-5-[(3,3-difluoro-2-oxo-1H-pyrrolo[2,3-b]pyridin-4-yl)sulfanyl]pyrazin-2-yl]-2-oxa-8-azaspiro[4.5]decan-4-yl]-2-methylpropane-2-sulfinamide Chemical compound CC(C)(C)[S@@](=O)N[C@@H]1COCC11CCN(CC1)c1cnc(Sc2ccnc3NC(=O)C(F)(F)c23)c(N)n1 UVNPEUJXKZFWSJ-LMTQTHQJSA-N 0.000 description 1
- ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 description 1
- NJZVZIKDQXGOIH-UHFFFAOYSA-N 1-oxido-6-propan-2-ylquinolin-1-ium Chemical compound [O-][N+]1=CC=CC2=CC(C(C)C)=CC=C21 NJZVZIKDQXGOIH-UHFFFAOYSA-N 0.000 description 1
- WDBQJSCPCGTAFG-QHCPKHFHSA-N 4,4-difluoro-N-[(1S)-3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-pyridin-3-ylpropyl]cyclohexane-1-carboxamide Chemical compound FC1(CCC(CC1)C(=O)N[C@@H](CCN1CCC(CC1)N1C(=NN=C1C)C(C)C)C=1C=NC=CC=1)F WDBQJSCPCGTAFG-QHCPKHFHSA-N 0.000 description 1
- BWGRDBSNKQABCB-UHFFFAOYSA-N 4,4-difluoro-N-[3-[3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]-1-thiophen-2-ylpropyl]cyclohexane-1-carboxamide Chemical compound CC(C)C1=NN=C(C)N1C1CC2CCC(C1)N2CCC(NC(=O)C1CCC(F)(F)CC1)C1=CC=CS1 BWGRDBSNKQABCB-UHFFFAOYSA-N 0.000 description 1
- FWUGFRIFQMEGKX-UHFFFAOYSA-N 4-(4-fluorophenyl)-3h-1,3-oxazol-2-one Chemical compound C1=CC(F)=CC=C1C1=COC(=O)N1 FWUGFRIFQMEGKX-UHFFFAOYSA-N 0.000 description 1
- BUIIQSIPZLULBF-UHFFFAOYSA-N 4-(4-methylphenyl)-3h-1,3-oxazol-2-one Chemical compound C1=CC(C)=CC=C1C1=COC(=O)N1 BUIIQSIPZLULBF-UHFFFAOYSA-N 0.000 description 1
- LRMGFEQLZDIREV-UHFFFAOYSA-N 4-chloro-1-oxidoquinolin-1-ium Chemical compound C1=CC=C2[N+]([O-])=CC=C(Cl)C2=C1 LRMGFEQLZDIREV-UHFFFAOYSA-N 0.000 description 1
- RFVVMGAZGKKIOZ-UHFFFAOYSA-N 4-ethyl-1,2-oxazol-3-one Chemical group CCC1=CONC1=O RFVVMGAZGKKIOZ-UHFFFAOYSA-N 0.000 description 1
- PTGKRMDLCPTLHU-UHFFFAOYSA-N 4-methyl-1,2-oxazol-3-one Chemical group CC1=CON=C1O PTGKRMDLCPTLHU-UHFFFAOYSA-N 0.000 description 1
- PSZUKCUBGTVVPJ-UHFFFAOYSA-N 6-bromo-1-oxidoquinolin-1-ium Chemical compound BrC1=CC=C2[N+]([O-])=CC=CC2=C1 PSZUKCUBGTVVPJ-UHFFFAOYSA-N 0.000 description 1
- VDSWYWODRNTZRB-UHFFFAOYSA-N 6-fluoro-1-oxidoquinolin-1-ium Chemical compound FC1=CC=C2[N+]([O-])=CC=CC2=C1 VDSWYWODRNTZRB-UHFFFAOYSA-N 0.000 description 1
- ULMCVDAJWJRBFH-UHFFFAOYSA-N 7-methyl-1-oxidoquinolin-1-ium Chemical compound C1=CC=[N+]([O-])C2=CC(C)=CC=C21 ULMCVDAJWJRBFH-UHFFFAOYSA-N 0.000 description 1
- PIOGDSHYODXWAK-UHFFFAOYSA-N 8-methyl-1-oxidoquinolin-1-ium Chemical compound C1=C[N+]([O-])=C2C(C)=CC=CC2=C1 PIOGDSHYODXWAK-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 235000021513 Cinchona Nutrition 0.000 description 1
- 241000157855 Cinchona Species 0.000 description 1
- 238000010499 C–H functionalization reaction Methods 0.000 description 1
- NUGPIZCTELGDOS-QHCPKHFHSA-N N-[(1S)-3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-pyridin-3-ylpropyl]cyclopentanecarboxamide Chemical compound C(C)(C)C1=NN=C(N1C1CCN(CC1)CC[C@@H](C=1C=NC=CC=1)NC(=O)C1CCCC1)C NUGPIZCTELGDOS-QHCPKHFHSA-N 0.000 description 1
- LFZAGIJXANFPFN-UHFFFAOYSA-N N-[3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-thiophen-2-ylpropyl]acetamide Chemical compound C(C)(C)C1=NN=C(N1C1CCN(CC1)CCC(C=1SC=CC=1)NC(C)=O)C LFZAGIJXANFPFN-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 229940111121 antirheumatic drug quinolines Drugs 0.000 description 1
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- KMPWYEUPVWOPIM-KODHJQJWSA-N cinchonidine Chemical compound C1=CC=C2C([C@H]([C@H]3[N@]4CC[C@H]([C@H](C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-KODHJQJWSA-N 0.000 description 1
- KMPWYEUPVWOPIM-UHFFFAOYSA-N cinchonidine Natural products C1=CC=C2C(C(C3N4CCC(C(C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-UHFFFAOYSA-N 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 1
- NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 description 1
- 229910001958 silver carbonate Inorganic materials 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
Abstract
The invention discloses a method for selectively synthesizing a 2-amido quinoline-N-oxide compound by using a quinoline-N-oxide compound, which is characterized in that copper tetrafluoroacetonitrile hexafluorophosphate and silver acetate are used as catalysts, isoxazolidinone is used as a nitrogen source, expensive ligands are not required to be added, and the product can be obtained through reaction under mild conditions. The method has the advantages of low cost, mild reaction conditions, high selectivity and the like, and avoids the use of noble metals such as rhodium, iridium, palladium and the like. The method is suitable for substrates such as quinoline-N-oxide compounds with different substitutions and other polysubstituted isoxazolidinones.
Description
Technical Field
The invention belongs to the technical field of activation of C-H bonds, and particularly relates to a method for selectively synthesizing 2-amido quinoline-N-oxide compounds based on copper hexafluorophosphate tetraacetonitrile and silver acetate catalysis quinoline-N-oxide compounds.
Background
Quinoline derivatives are important starting materials and intermediates in the chemical industry and are widely used to synthesize a variety of chemical products including various dyes, pharmaceutical products, agricultural chemicals, and the like. In particular, the synthesis of quinolines is very important in the fields of pharmaceutical chemistry and organic synthetic chemistry, such as: cinchonidine and cinchona alkaloid, and the like. In addition, detection of microbial and anti-cancer activity of 2-amidoquinoline-N-oxide has also been reported (antibodies & chemotherapy (Northfield, ill.), 1956,6,261-267; J.org.chem.,1961,26,2831-2833). Therefore, it is highly desirable to achieve efficient synthesis of 2-amidoquinolines and derivatives thereof by simple direct C-H bond activation.
In 2013, li Gang reports a system using copper acetate as a catalyst, silver carbonate as an oxidant and lactam as a nitrogen source to activate C-H bond of quinoline-N-oxide, thereby synthesizing various derivatives of 2-aminoquinoline-N-oxide. The method has lower catalyst loading and good functional group compatibility. Furthermore, the catalytic system likewise allows the reaction of cyclohexylamine and cyclopentylamine (org. Lett.,2013,15,5198-5201).
In 2014, cui Xiuling reports that the activation of C-H bond of quinoline-N-oxide is achieved under mild condition by using 10mol% of CuI as catalyst, air as oxidant, cyclic amine and common secondary amine as nitrogen source, and 2-aminoquinoline-N-oxide and its derivatives are synthesized (Org. Lett.,2014,16,1840-1843).
In 2017, samanta subject group CuI is taken as a catalyst, sp 2 N is taken as a nitrogen source, C-H bond activation of quinoline-N-oxide is realized, synthesis research of 2-arylaminoquinoline-N-oxide is realized for the first time, and the reaction has excellent universality and atom economy. Furthermore, the subject was based on the synthesis of a series of compounds possessing a highly conjugated system using this method (J.Org.chem., 2017,82,8933-8942)
The above method has limitations of substrate, and can only synthesize tertiary amine, aromatic amine and the like, and cannot be used for synthesizing secondary amine and primary amine. Secondly, the method has the defects of overlong reaction time, strict reaction temperature condition, complex operation and the like, thereby bringing about certain environmental pollution and economic cost problems, and particularly the problems are serious in the large-scale industrial production process. Therefore, developing a mild and efficient strategy for preparing the 2-amido quinoline-N-oxide has important scientific research significance.
Disclosure of Invention
The invention aims to provide a synthesis method for selectively synthesizing 2-amidoquinoline-N-oxide compounds by catalyzing quinoline-N-oxide compounds with copper tetraacetonitrile hexafluorophosphate and silver acetate.
Aiming at the purposes, the invention adopts the technical scheme that: reacting a quinoline-N-oxide compound shown in a formula I with isoxazolidinone shown in a formula II in dichloroethane for 12-24 hours at 75-85 ℃ by using copper hexafluorophosphate and silver acetate as catalysts, and separating and purifying after the reaction is finished to obtain a 2-amido quinoline-N-oxide compound shown in a formula I';
Wherein R 1 represents any one of H, C 1～C6 alkyl, C 1～C4 alkoxy and halogen; r 2 represents any one of H, C 1～C6 alkyl, phenyl, C 1～C4 alkyl substituted phenyl, C 1～C4 alkoxy substituted phenyl, halogenated phenyl, C 1～C6 alkyl and C 3～C6 cycloalkyl. Preferably, R 1 represents any one of fluorine, chlorine, bromine, methyl, isopropyl and methoxy, and R 2 represents any one of H, methyl, phenyl, methyl-substituted phenyl, ethyl-substituted phenyl, fluorophenyl, methyl, ethyl and cyclopropyl.
In the above synthesis method, the addition amount of the copper tetraacetonitrile hexafluorophosphate is preferably 15 to 25% of the molar amount of the quinoline-N-oxide compound, and the addition amount of the silver acetate is preferably 15 to 25% of the molar amount of the quinoline-N-oxide compound.
In the above synthetic method, the amount of the isoxazolidinone added is preferably 2 to 3 times the molar amount of the quinoline-N-oxide compound.
In the above synthesis method, it is preferable to react in air at 80℃for 12 to 24 hours.
Compared with the prior art, the invention has the following beneficial effects:
1. the synthesis method of the invention reports that the copper tetraacetonitrile hexafluorophosphate and silver acetate catalytic system is used for synthesizing the 2-amido quinoline-N-oxide compound for the first time, and provides a new thought for the subsequent C-H activation research of the No. 2 position of the quinoline-N-oxide compound.
2. The synthesis method is simple and green, and the isoxazolidinone is used as a nitrogen source, so that the reaction safety is improved.
3. The method has the advantages of mild reaction conditions, simple operation and high selectivity of target products.
4. The catalyst used in the invention is commercially available, is environment-friendly, and has low preparation cost and simple operation.
5. The invention has good substrate universality, is suitable for various quinoline-N-oxides, and can be well compatible with some halogen and other reducing functional groups.
Detailed Description
The present invention will be described in further detail with reference to examples, but the scope of the present invention is not limited to these examples.
Example 1
Synthesis of Compound 1 of the formula
Quinoline-N-oxide (40.0 mg,0.28 mmol), phenylisoxazolone (91.4 mg,0.56 mmol), copper tetraacetonitrile hexafluorophosphate (20.9 mg,0.056 mmol), silver acetate (9.3 mg,0.056 mmol) were dissolved in 4mL of dichloroethane, heated to 80℃and reacted for 12h. After completion of the reaction, quench with 0.5mL hydrochloric acid and 10mL saturated ammonium chloride, extract with dichloromethane (5 mL x 3), dry over anhydrous sodium sulfate, concentrate under vacuum and purify by column chromatography (dichloromethane: ethyl acetate=1:2) to give compound 1 as an off-white solid, 54.0mg, in 73% yield.
The spectrum data of the obtained product are ：1H NMR(400MHz,CDCl3):δ＝11.31(bs,1H),8.78(d,J＝8.0Hz,1H),8.65(d,J＝8.0Hz,1H),8.06(d,J＝8.0Hz,2H),7.87-7.81(m,3H),7.53-7.64(m,4H);13C NMR(100MHz,CDCl3):δ＝165.8,139.3,138.2,133.3,133.2,131.4,129.1,128.4,127.9,127.0,125.8,118.8,113.0.
Example 2
Synthesis of Compound 2 of the formula
In this example, the quinoline-N-oxide in example 1 was replaced with an equimolar amount of 8-methylquinoline-N-oxide, and the other procedure was the same as in example 1 to give compound 2 in 54% yield.
The spectrum data of the obtained product are ：1H NMR(400MHz,CDCl3)δ＝11.47(bs,1H),8.72(d,J＝8.0Hz,1H),8.07(d,J＝8.0Hz,2H),7.77(d,J＝8.0Hz,1H),7.64-7.58(m,2H),7.53-7.49(m,2H),7.45(d,J＝8.0Hz,1H),7.36(t,8.0Hz,1H),3.22(s,3H);13CNMR(100MHz,CDCl3)δ＝165.9,143.3,139.0,134.4,133.5,133.0,132.1,129.0,128.7,127.9,127.6,127.2,126.6,112.9,24.8..
Example 3
Synthesis of Compound 3 of the formula
In this example, the quinoline-N-oxide in example 1 was replaced with an equimolar amount of 6-bromoquinoline-N-oxide, and the other procedure was the same as in example 1 to obtain compound 3 in 57% yield.
The spectrum data of the obtained product are ：1H NMR(400MHz,CDCl3)δ＝11.22(bs,1H),8.84(d,J＝8.0Hz,1H),8.63(d,J＝8.0Hz,1H),8.19(d,J＝8.0Hz,1H),8.06(d,J＝8.0Hz,2H),7.82(d,J＝8.0Hz,1H),7.56-7.51(m,4H);13C NMR(100MHz,CDCl3)δ＝165.7,142.6,140.1,133.3,133.0,131.4,130.9,129.1,127.9,127.6,125.1,122.7,118.7,113.9.
Example 4
Synthesis of Compound 4 of the formula
In the examples, the quinoline-N-oxide in example 1 was replaced with an equimolar amount of 7-methylquinoline-N-oxide, and the other steps were the same as in example 1 to give compound 4 in a yield of 71%.
The spectrum data of the obtained product are ：1H NMR(400MHz,CDCl3)δ＝11.31(bs,1H),8.68(d,J＝8.0Hz,1H),8.44(s,1H),8.07(d,J＝8.0Hz,2H),7.82(d,J＝8.0Hz,1H),7.74(d,J＝8.0Hz,1H),7.63-7.53(m,3H),7.40(d,J＝8.0Hz,1H),2.60(s,3H);13C NMR(100MHz,CDCl3)δ＝165.8,142.5,139.2,133.4,133.1,132.6,131.0,130.7,129.1,128.1,127.9,127.4,124.0,117.9,112.1,22.4.
Example 5
Synthesis of Compound 5 of the formula
In the example, the quinoline-N-oxide in example 1 was replaced with an equimolar amount of 4-chloroquinoline-N-oxide, and the other procedure was the same as in example 1 to give compound 5 in 73% yield.
The spectrum data of the obtained product are ：1H NMR(400MHz,CDCl3)δ＝11.22(bs,1H),8.95(s,1H),8.68(d,J＝8.0Hz,1H),8.21(d,J＝8.0Hz,1H),8.06(d,J＝8.0Hz,2H),7.86(t,J＝8.0Hz,1H),7.53-7.69(m,4H);13C NMR(100MHz,CDCl3)δ＝165.7,141.9,139.6,133.4,133.0,132.1,129.2,127.9,127.8,125.4,123.8,119.3,113.2.
Example 6
Synthesis of Compound 6 of the formula
In this example, the quinoline-N-oxide in example 1 was replaced with an equimolar amount of 6-fluoroquinoline-N-oxide, and the other steps were the same as in example 1 to obtain compound 6 in a yield of 75%.
The spectrum data of the obtained product are 1H NMR(400MHz,CDCl3)δ＝11.17(bs,1H),8.80(d,J＝8.0Hz,1H),8.67(bs,1H),8,05(d,J＝8.0Hz,2H),7.78(d,J＝8.0Hz,1H),7.64-7.48(m,5H);13C NMR(100MHz,CDCl3)δ＝165.7,160.1(d,J＝250Hz),142.0,136.3,133.2,133.2,127.9,127.2,126.6(d,J＝10Hz),121.6(d,J＝10Hz),121.0(d,J＝26Hz),114.4,112.0(d,J＝23Hz).
Example 7
Synthesis of Compound 7 of the formula
In this example, the quinoline-N-oxide in example 1 was replaced with an equimolar amount of 6-isopropylquinoline-N-oxide, and the other steps were the same as in example 1 to obtain compound 7 in a yield of 72%.
The spectrum data of the obtained product are ：1H NMR(400MHz,CDCl3)δ＝11.25(bs,1H),8.71(d,J＝8.0Hz,1H),8.53(d,J＝8.0Hz,1H),8.02(d,J＝8.0Hz,1H),7.79(d,J＝7.9Hz,1H),6.67(d,J＝8.0Hz,1H),6.61(d,J＝8.0Hz,1H),7.48-7.58(m,4H),3.05(septet,J＝4Hz,1H),1.31(d,J＝4.0Hz,6H);13C NMR(100MHz,CDCl3)δ＝165.7,147.8,137.8,133.3,133.0,131.2,129.0,128.0,127.8,126.0,124.6,118.6,113.0,33.9,23.8.
Example 8
Synthesis of Compound 8 of the formula
In this example, the phenyl isoxazolone of example 1 was replaced with equimolar 4-fluorophenyl oxazolone, and the other steps were the same as in example 1 to give compound 8 in 78% yield.
The spectrum data of the obtained product are ：1H NMR(400MHz,CDCl3)δ＝11.27(bs,1H),8.74(d,J＝8.0Hz,1H),8.65(d,J＝8.0Hz,1H),8.08(dd,J＝4.0,4.0Hz,2H),7.86-7.78(m,3H),7.59(t,J＝8.0Hz,3H),7.23(t,J＝8.0Hz,2H);13C NMR(100MHz,CDCl3)δ＝166.6(d,J＝253Hz),164.6,139.2,131.4,130.5,130.4,29.5,128.4,127.1,125.8,118.7,116.4,116.2,113.0.
Example 9
Synthesis of Compound 9 of the formula
In this example, the phenyl isoxazolone of example 1 was replaced with equimolar (4-methyl) phenyl oxazolone, and the other steps were the same as in example 1 to give compound 9 in 79% yield.
The spectrum data of the obtained product are ：1H NMR(400MHz,CDCl3)δ＝11.24(bs,1H),8.76(d,J＝8.0Hz,1H),8.64(d,J＝8.0Hz,1H),7.96(d,J＝8.0Hz,2H),7.85-7.77(m,3H),7.56(t,J＝8.0Hz,1H),7.33(d,J＝8.0Hz,1H),2.43(s,3H);13C NMR(100MHz,CDCl3)δ＝165.6,144.0,142.4,139.2,131.3,130.4,129.8,128.3,127.9,126.9,118.7,113.1,21.7.
Example 10
Synthesis of Compound 10 of the formula
In this example, the phenylisoxazolone of example 1 was replaced with equimolar (4-ethyl) phenyloxazolone, and the other steps were the same as in example 1 to give compound 10 in 68% yield.
The spectrum data of the obtained product are ：1H NMR(400MHz,CDCl3)δ＝11.29(bs,1H),8.77(d,J＝8.0Hz,1H),8.66(d,J＝8.0Hz,1H),7.86(d,J＝8.0Hz,2H),7.88-7.79(m,3H),7.58(t,J＝8.0Hz,1H),7.37(d,J＝8.0Hz,1H),2.65(q,J＝8.2Hz,2H),1.18(t,J＝8.1Hz,3H);13C NMR(100MHz,CDCl3)δ＝165.8,150.2,142.5,139.2,131.4,130.7,128.6,118.8,113.21,29.0,15.3.
Example 11
Synthesis of Compound 11 of the formula
In this example, phenyl isoxazolone (91.4 mg,0.56 mmol) in example 1 was replaced with methyl isoxazolone (72.72 mg,0.72 mmol), the reaction time was prolonged to 24h, and the other steps were the same as in example 1 to give compound 11 as an off-white solid in 89% yield.
The spectrum data of the obtained product are ：1H NMR(400MHz,DMSO-d6)δ＝10.8(bs,1H),8.43(t,J＝8.0Hz,2H),7.98-7.91(m,2H),7.77(t,J＝8.1Hz,1H),7.58(d,J＝8.1Hz,1H),2.28(s,3H);13C NMR(100MHz,DMSO-d6)δ＝170.4,141.6,139.1,131.0,128.6,127.0,126.6,125.6,118.3,113.6,24.7.
Example 12
Synthesis of Compound 12 of the formula
In this example, phenyl isoxazolone (91.4 mg,0.56 mmol) in example 1 was replaced with ethyl isoxazolone (82.8 mg,0.72 mmol), the reaction time was prolonged to 24h, and the other steps were the same as in example 1 to give compound 12 as an off-white solid in 73% yield.
The spectrum data of the obtained product are ：1H NMR(400MHz,CDCl3)δ＝10.4(bs,1H),8.72(d,J＝8.0Hz,2H),7.88-7.71(m,3H),7.51(t,J＝8.1Hz,1H),2.62(q,J＝8.3Hz,2H),2.62(q,J＝8.3Hz,2H),1,25(t,J＝8.3Hz,3H);13C NMR(100MHz,CDCl3)δ＝173.5,142.1,139.0,131.0,128.7,127.3,126.7,125.8,118.6,113.2,31.7,9.8.
Example 13
Synthesis of Compound 13 of the formula
In this example, phenyl isoxazolone (91.4 mg,0.56 mmol) in example 1 was replaced with cyclopropyl isoxazolone (91.4 mg,0.72 mmol), the reaction time was prolonged to 24h, and the other steps were the same as in example 1 to give compound 13 as an off-white solid in 91% yield.
The spectral data of the obtained product were: the spectrum data of the obtained product are ：1H NMR(400MHz,DMSO-d6)δ＝10.8(bs,1H),8.43(d,J＝8.0Hz,1H),8.39(d,J＝8.1Hz,1H),7.93(d,J＝7.8Hz,1H),7.88(d,J＝7.9Hz,1H),7.74(t,J＝8.1Hz,1H),7.54(t,J＝8.0Hz,1H),2.42(t,J＝7.3Hz,1H),0.82(d,,J＝7.2Hz,4H);13C NMR(100MHz,DMSO-d6)δ＝174.1,141.9,139.5,131.4,129.0,127.4,127.0,126.0,118.7,114.2,15.3,9.4.
Claims (5)
1. A method for selectively synthesizing 2-amido quinoline-N-oxide compounds by quinoline-N-oxide compounds is characterized in that: reacting a quinoline-N-oxide compound shown in a formula I with isoxazolidinone shown in a formula II in dichloroethane for 12-24 hours at 75-85 ℃ by using copper hexafluorophosphate and silver acetate as catalysts, and separating and purifying after the reaction is finished to obtain a 2-amido quinoline-N-oxide compound shown in a formula I';
Wherein R 1 represents any one of H, C 1～C6 alkyl, C 1～C4 alkoxy and halogen; r 2 represents any one of H, C 1～C6 alkyl, phenyl, C 1～C4 alkyl substituted phenyl, C 1～C4 alkoxy substituted phenyl, halogenated phenyl, C 1～C6 alkyl and C 3～C6 cycloalkyl.
2. The method for selectively synthesizing 2-amido quinoline-N-oxide based compound according to claim 1, wherein the method comprises the following steps: r 1 represents any one of fluorine, chlorine, bromine, methyl, isopropyl and methoxy, R 2 represents any one of H, methyl, phenyl, methyl substituted phenyl, ethyl substituted phenyl, fluorophenyl, methyl, ethyl and cyclopropyl.
3. The method for selectively synthesizing 2-amido quinoline-N-oxide compounds according to claim 1 or 2, characterized in that: the addition amount of the copper tetrafluoroacetonitrile hexafluorophosphate is 15-25% of the molar amount of the quinoline-N-oxide compound, and the addition amount of the silver acetate is 15-25% of the molar amount of the quinoline-N-oxide compound.
4. The method for selectively synthesizing 2-amido quinoline-N-oxide compounds according to claim 1 or 2, characterized in that: the addition amount of the isoxazolidinone is 2-3 times of the molar amount of the quinoline-N-oxide compound.
5. The method for selectively synthesizing 2-amido quinoline-N-oxide compounds according to claim 1 or 2, characterized in that: reacting for 12-24 hours at 80 ℃ in the air.
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