CN108033919B - Method for synthesizing 2-phenyl quinazolinone compound by taking styrene compound as raw material - Google Patents
Method for synthesizing 2-phenyl quinazolinone compound by taking styrene compound as raw material Download PDFInfo
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- CN108033919B CN108033919B CN201810122265.7A CN201810122265A CN108033919B CN 108033919 B CN108033919 B CN 108033919B CN 201810122265 A CN201810122265 A CN 201810122265A CN 108033919 B CN108033919 B CN 108033919B
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- aminobenzamide
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- -1 styrene compound Chemical class 0.000 title claims abstract description 25
- 238000000034 method Methods 0.000 title claims abstract description 21
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 18
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Natural products C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 title claims abstract description 16
- 239000002994 raw material Substances 0.000 title claims abstract description 16
- 238000006243 chemical reaction Methods 0.000 claims abstract description 84
- PXBFMLJZNCDSMP-UHFFFAOYSA-N 2-Aminobenzamide Chemical compound NC(=O)C1=CC=CC=C1N PXBFMLJZNCDSMP-UHFFFAOYSA-N 0.000 claims abstract description 44
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 40
- 239000003054 catalyst Substances 0.000 claims abstract description 24
- 239000003446 ligand Substances 0.000 claims abstract description 24
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 16
- 239000001301 oxygen Substances 0.000 claims abstract description 13
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 13
- 239000001257 hydrogen Substances 0.000 claims abstract description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 11
- 230000009471 action Effects 0.000 claims abstract description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 3
- 239000000460 chlorine Chemical group 0.000 claims abstract description 3
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 3
- 239000011737 fluorine Chemical group 0.000 claims abstract description 3
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 48
- 239000007810 chemical reaction solvent Substances 0.000 claims description 23
- 150000001875 compounds Chemical class 0.000 claims description 22
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical group N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 claims description 20
- PBDBXAQKXCXZCJ-UHFFFAOYSA-L palladium(2+);2,2,2-trifluoroacetate Chemical compound [Pd+2].[O-]C(=O)C(F)(F)F.[O-]C(=O)C(F)(F)F PBDBXAQKXCXZCJ-UHFFFAOYSA-L 0.000 claims description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzenecarboxaldehyde Natural products O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims description 6
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 5
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims description 4
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical group [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 3
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 3
- 238000009833 condensation Methods 0.000 claims description 3
- 230000005494 condensation Effects 0.000 claims description 3
- 238000005859 coupling reaction Methods 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- 238000011049 filling Methods 0.000 claims description 2
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 2
- DHDHJYNTEFLIHY-UHFFFAOYSA-N 4,7-diphenyl-1,10-phenanthroline Chemical compound C1=CC=CC=C1C1=CC=NC2=C1C=CC1=C(C=3C=CC=CC=3)C=CN=C21 DHDHJYNTEFLIHY-UHFFFAOYSA-N 0.000 claims 1
- 125000005245 nitryl group Chemical group [N+](=O)([O-])* 0.000 claims 1
- 230000035484 reaction time Effects 0.000 abstract description 4
- 150000003440 styrenes Chemical class 0.000 abstract description 3
- 238000009776 industrial production Methods 0.000 abstract description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract description 2
- 238000002360 preparation method Methods 0.000 abstract description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 abstract 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 32
- 239000000047 product Substances 0.000 description 31
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- 238000005481 NMR spectroscopy Methods 0.000 description 16
- 238000001228 spectrum Methods 0.000 description 16
- AVRPFRMDMNDIDH-UHFFFAOYSA-N 1h-quinazolin-2-one Chemical class C1=CC=CC2=NC(O)=NC=C21 AVRPFRMDMNDIDH-UHFFFAOYSA-N 0.000 description 14
- 230000015572 biosynthetic process Effects 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- 239000007858 starting material Substances 0.000 description 11
- 238000000746 purification Methods 0.000 description 10
- 238000000926 separation method Methods 0.000 description 10
- 238000004440 column chromatography Methods 0.000 description 9
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- 229910052799 carbon Inorganic materials 0.000 description 8
- 239000003480 eluent Substances 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 230000000845 anti-microbial effect Effects 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000003814 drug Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 4
- QMNUDYFKZYBWQX-UHFFFAOYSA-N 1H-quinazolin-4-one Chemical class C1=CC=C2C(=O)N=CNC2=C1 QMNUDYFKZYBWQX-UHFFFAOYSA-N 0.000 description 3
- WQRWUSWJYHBQNF-UHFFFAOYSA-N 4-phenyl-1,10-phenanthroline Chemical compound C1=CC=CC=C1C1=CC=NC2=C1C=CC1=CC=CN=C21 WQRWUSWJYHBQNF-UHFFFAOYSA-N 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 150000007660 quinolones Chemical class 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000009987 spinning Methods 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- UKSZBOKPHAQOMP-SVLSSHOZSA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 UKSZBOKPHAQOMP-SVLSSHOZSA-N 0.000 description 1
- JZEKLNQRYWDABI-SDQBBNPISA-N (3z)-6-chloro-3-(pyridin-3-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC(Cl)=CC=C2\C1=C\C1=CC=CN=C1 JZEKLNQRYWDABI-SDQBBNPISA-N 0.000 description 1
- KYVBNYUBXIEUFW-UHFFFAOYSA-N 1,1,3,3-tetramethylguanidine Chemical compound CN(C)C(=N)N(C)C KYVBNYUBXIEUFW-UHFFFAOYSA-N 0.000 description 1
- WGGLDBIZIQMEGH-UHFFFAOYSA-N 1-bromo-4-ethenylbenzene Chemical compound BrC1=CC=C(C=C)C=C1 WGGLDBIZIQMEGH-UHFFFAOYSA-N 0.000 description 1
- KTZVZZJJVJQZHV-UHFFFAOYSA-N 1-chloro-4-ethenylbenzene Chemical compound ClC1=CC=C(C=C)C=C1 KTZVZZJJVJQZHV-UHFFFAOYSA-N 0.000 description 1
- CEWDRCQPGANDRS-UHFFFAOYSA-N 1-ethenyl-4-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(C=C)C=C1 CEWDRCQPGANDRS-UHFFFAOYSA-N 0.000 description 1
- JWVTWJNGILGLAT-UHFFFAOYSA-N 1-ethenyl-4-fluorobenzene Chemical compound FC1=CC=C(C=C)C=C1 JWVTWJNGILGLAT-UHFFFAOYSA-N 0.000 description 1
- UAJRSHJHFRVGMG-UHFFFAOYSA-N 1-ethenyl-4-methoxybenzene Chemical compound COC1=CC=C(C=C)C=C1 UAJRSHJHFRVGMG-UHFFFAOYSA-N 0.000 description 1
- YFZHODLXYNDBSM-UHFFFAOYSA-N 1-ethenyl-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(C=C)C=C1 YFZHODLXYNDBSM-UHFFFAOYSA-N 0.000 description 1
- OHJPGUSXUGHOGE-UHFFFAOYSA-N 2-methyl-6-(6-methylpyridin-2-yl)pyridine Chemical compound CC1=CC=CC(C=2N=C(C)C=CC=2)=N1 OHJPGUSXUGHOGE-UHFFFAOYSA-N 0.000 description 1
- VDULOAUXSMYUMG-UHFFFAOYSA-N 2-phenyl-1h-quinazolin-4-one Chemical compound N=1C2=CC=CC=C2C(O)=NC=1C1=CC=CC=C1 VDULOAUXSMYUMG-UHFFFAOYSA-N 0.000 description 1
- OFDVABAUFQJWEZ-UHFFFAOYSA-N 3-pyridin-3-ylpyridine Chemical group C1=CN=CC(C=2C=NC=CC=2)=C1 OFDVABAUFQJWEZ-UHFFFAOYSA-N 0.000 description 1
- JLBJTVDPSNHSKJ-UHFFFAOYSA-N 4-Methylstyrene Chemical compound CC1=CC=C(C=C)C=C1 JLBJTVDPSNHSKJ-UHFFFAOYSA-N 0.000 description 1
- NBPGPQJFYXNFKN-UHFFFAOYSA-N 4-methyl-2-(4-methylpyridin-2-yl)pyridine Chemical compound CC1=CC=NC(C=2N=CC=C(C)C=2)=C1 NBPGPQJFYXNFKN-UHFFFAOYSA-N 0.000 description 1
- IOQMOSNHRJJVGR-UHFFFAOYSA-N 6-(4-nitrophenyl)-1H-quinazolin-2-one Chemical compound [N+](=O)([O-])C1=CC=C(C=C1)C=1C=C2C=NC(NC2=CC=1)=O IOQMOSNHRJJVGR-UHFFFAOYSA-N 0.000 description 1
- PTRATZCAGVBFIQ-UHFFFAOYSA-N Abametapir Chemical compound N1=CC(C)=CC=C1C1=CC=C(C)C=N1 PTRATZCAGVBFIQ-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 239000005411 L01XE02 - Gefitinib Substances 0.000 description 1
- 239000005551 L01XE03 - Erlotinib Substances 0.000 description 1
- 244000207740 Lemna minor Species 0.000 description 1
- 235000006439 Lemna minor Nutrition 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- LHPXYPROPRFEQE-UHFFFAOYSA-N Methylhalfordinol Chemical compound C1=CC(OC)=CC=C1C1=CN=C(C=2C=NC=CC=2)O1 LHPXYPROPRFEQE-UHFFFAOYSA-N 0.000 description 1
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- TWKVUTXHANJYGH-UHFFFAOYSA-L allyl palladium chloride Chemical compound Cl[Pd]CC=C.Cl[Pd]CC=C TWKVUTXHANJYGH-UHFFFAOYSA-L 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- DKVNPHBNOWQYFE-UHFFFAOYSA-N carbamodithioic acid Chemical group NC(S)=S DKVNPHBNOWQYFE-UHFFFAOYSA-N 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 150000004659 dithiocarbamates Chemical class 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000009982 effect on human Effects 0.000 description 1
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 1
- 229960001433 erlotinib Drugs 0.000 description 1
- KBPUBCVJHFXPOC-UHFFFAOYSA-N ethyl 3,4-dihydroxybenzoate Chemical compound CCOC(=O)C1=CC=C(O)C(O)=C1 KBPUBCVJHFXPOC-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 229960002584 gefitinib Drugs 0.000 description 1
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 description 1
- 150000002431 hydrogen Chemical group 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 208000025113 myeloid leukemia Diseases 0.000 description 1
- KVKFRMCSXWQSNT-UHFFFAOYSA-N n,n'-dimethylethane-1,2-diamine Chemical compound CNCCNC KVKFRMCSXWQSNT-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- JKDRQYIYVJVOPF-FDGPNNRMSA-L palladium(ii) acetylacetonate Chemical compound [Pd+2].C\C([O-])=C\C(C)=O.C\C([O-])=C\C(C)=O JKDRQYIYVJVOPF-FDGPNNRMSA-L 0.000 description 1
- INIOZDBICVTGEO-UHFFFAOYSA-L palladium(ii) bromide Chemical compound Br[Pd]Br INIOZDBICVTGEO-UHFFFAOYSA-L 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/88—Oxygen atoms
- C07D239/91—Oxygen atoms with aryl or aralkyl radicals attached in position 2 or 3
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for synthesizing 2-phenyl quinazolinone compounds, which takes styrene compounds and 2-aminobenzamide as reaction raw materials, and the reaction is carried out under the combined action of palladium catalyst, ligand and oxygen to obtain the 2-phenyl quinazolinone compounds, wherein the reaction temperature is 80-110 ℃, and the reaction equation is as follows:
Description
Technical Field
The invention relates to a synthesis method of a compound, in particular to a method for synthesizing a 2-phenyl quinazolinone compound by taking a styrene compound as a raw material, belonging to the technical field of organic compound synthesis.
Background
Quinazolinone compounds are important nitrogen-containing heterocyclic compounds containing a benzo pyrimidone skeleton, and exist in a plurality of natural alkaloids, such as: dichroine, camelinine, sanocinine and the like. Quinazolinone compounds exhibit wide application potential because the quinazolinone skeleton is easily modified by various functional groups, and in particular in the field of medicine, quinazolinone active molecules are concerned by researchers because of the advantages of low toxicity, high efficiency, unique action mode and the like.
In the antimicrobial field, with the wide use and even abuse of antibiotics such as quinolones in recent years, drug-resistant strains are frequently generated, so that the drug effects of many clinical antimicrobial drugs are greatly reduced or even completely ineffective, and the development of novel high-efficiency antimicrobial drugs is urgent. Quinazolinones, important derivative structures as antibacterial agents quinolones, show great potential for development in the antimicrobial field. Studies have shown that the 2-and 3-positions of quinazolinones are important sites for affecting antimicrobial activity and are also easily modified, and thus numerous researchers have performed a number of structural modifications of the 2-and 3-positions to evaluate their antimicrobial activity and have achieved excellent results.
Just because of the importance of quinazolinone compounds, the synthesis and clinical trials of quinazolinone drugs have become the focus of scientific research, such as:
(1) in 2001, Connolly and the like react 2-aminobenzoic acid with imido ester compounds to generate corresponding 2-alkyl or 2-aryl substituted 4(3H) -quinazolinone compounds, the yield is 75-97%, and bioactivity tests show that the compounds have good bioactivity and show excellent activity in the aspects of inflammation resistance, hypertension resistance and bacteria resistance;
(2) in 2007, von Lemna minor and the like introduce various dithiocarbamate side chains into 6-site of 4(3H) -quinazolinone to synthesize a series of fluorophenylpiperazinyl dithiocarbamate compounds containing quinazolinone, and the results of screening of anticancer activity show that: among the obtained compounds, 4- (4-fluorophenyl) piperazine dithioformate containing quinazolinone has the strongest activity and has a remarkable inhibitory effect on the in vitro growth of human myeloid leukemia K562 cells (IC50 is 0.5 mol/L);
(3) in 2008, as shown by bioactivity screening results, erlotinib is obtained by using 3, 4-dihydroxy ethyl benzoate as a raw material through a series of reactions: the compound with the basic structure of the quinazoline ring has a certain degree of in-vitro inhibition effect on human lung cancer cells A549, and the activity of the compound is equivalent to that of gefitinib.
Therefore, the design and synthesis of novel molecules containing quinazolinone structural elements and the research of synthetic strategies of quinazolinone derivatives with different structures have important theoretical innovative significance undoubtedly, and lay the foundation for screening quinazolinone derivatives with excellent activity.
Disclosure of Invention
The invention aims to provide a method for synthesizing 2-phenylquinazolinone compounds, which takes cheap and easily available styrene compounds as raw materials, has short reaction time and simple operation and is easy for post-treatment.
In order to achieve the above object, the present invention adopts the following technical solutions:
the method for synthesizing the 2-phenylquinazolinone compound is characterized in that a styrene compound and 2-aminobenzamide are used as reaction raw materials, under the combined action of a palladium catalyst, a ligand and oxygen, carbon-carbon bonds of the styrene compound are broken to generate a benzaldehyde compound, and the generated benzaldehyde compound and the 2-aminobenzamide are subjected to intermolecular condensation coupling reaction to obtain the 2-phenylquinazolinone compound, wherein the reaction temperature is 80-110 ℃, and the reaction equation is as follows:
in the formula, R is hydrogen, fluorine, chlorine, bromine, methyl, trifluoromethyl, nitro or methoxyl.
The method for synthesizing the 2-phenylquinazolinone compound is characterized by comprising the following steps of:
step 1: adding 2-aminobenzamide, a palladium catalyst and a ligand into a reaction vessel, and then continuously performing air extraction-oxygen filling operation on the reaction vessel for 3 times;
step 2: continuously adding a styrene compound and a reaction solvent into the reaction vessel, and reacting at the reaction temperature of 80-110 ℃ until the reaction is finished;
step 3: and separating and purifying the mixture obtained by the reaction.
The method for synthesizing the 2-phenylquinazolinone compound is characterized in that the molar ratio of the 2-aminobenzamide to the styrene compound is 1: 1-1: 3.
The method for synthesizing the 2-phenylquinazolinone compound is characterized in that the palladium catalyst is palladium acetate or palladium trifluoroacetate.
The method for synthesizing the 2-phenylquinazolinone compound is characterized in that the molar ratio of the palladium catalyst to the 2-aminobenzamide is 1: 10-1: 100.
The method for synthesizing the 2-phenylquinazolinone compound is characterized in that the ligand is at least one of 2,2 ' -bipyridine, 4 ' -dimethyl-2, 2 ' -bipyridine, 5 ' -dimethyl-2, 2 ' -bipyridine, 1, 10-phenanthroline and 4, 7-phenyl-1, 10-phenanthroline.
The method for synthesizing the 2-phenylquinazolinone compound is characterized in that the molar ratio of the ligand to the 2-aminobenzamide is 1: 5-1: 100.
The method for synthesizing the 2-phenylquinazolinone compound is characterized in that the reaction solvent is at least one of 3-dimethyl-2-imidazolidinone, dimethyl sulfoxide, tetrahydrofuran and N, N-dimethylacetamide.
The invention has the advantages that:
1. the raw material styrene compound is cheap and easy to obtain, and is more economical;
2. the preparation process is simple and convenient to operate, and the obtained product is easy to post-treat and suitable for large-scale industrial production;
3. high temperature and high pressure are not needed, and the reaction condition is mild;
4. the reaction time is short;
5. the reaction is efficient, the yield is high, and the reaction efficiency is higher after the reaction is amplified.
Detailed Description
The invention utilizes the carbon-carbon bond fracture of the styrene compound to generate the benzaldehyde compound, and the generated benzaldehyde compound and 2-aminobenzamide are subjected to intermolecular condensation coupling reaction, thereby preparing the quinazolinone compound.
The present invention will be described in detail with reference to the following embodiments.
Example 1: synthesis of 2-phenylquinazolinones
Starting material 2-aminobenzamide (0.3mmol, 1equiv), catalyst palladium trifluoroacetate (Pd (TFA)20.03mmol, 10%) and ligand 2, 2' -bipyridine (bpy, 0.06mmol, 20%) were added to the reaction vessel, the reaction vessel was subjected to 3 consecutive pump-oxygen operations, and then the reaction solvent dimethylsulfoxide (DMSO, 0.4mL) and the starting material styrene (0.9mmol, 3equiv) were added to the reaction vessel, followed by stirring in an oil bath at a reaction temperature of 100 ℃ until the reaction was complete (about 12 h).
The mixture obtained after the reaction can be further separated and purified, for example: extraction, column chromatography, distillation, decantation, filtration, centrifugation, washing, evaporation, stripping and adsorption to obtain a purer final product.
Of course, if desired, the mixture obtained after the reaction may also be subjected to a pretreatment such as: concentrating, extracting, distilling under reduced pressure, and introducing into other processes for reaction to produce other products, or directly introducing into other processes without pretreatment.
In this example, we used the following specific separation and purification method:
directly removing the reaction solvent by spinning off, and then separating by column chromatography (silica gel with 300-400 meshes is filled in the column, and the volume ratio of dichloromethane to ethyl acetate is 10: 1 is used as an eluent) to obtain a product after separation and purification.
After separation and purification, a white solid is obtained with the yield of 85 percent.
The data of the nuclear magnetic resonance hydrogen spectrum of the obtained product are as follows:
1H NMR(400MHz,DMSO-d6)δ:12.53(1H,s),8.15-8.20(3H,m),7.81-7.85(1H,m),7.74(1H,d),7.50-7.61(4H,m)。
the data of the nuclear magnetic resonance carbon spectrum of the obtained product are as follows:
13C NMR(100MHz,DMSO-d6)δ:162.1,152.2,148.6,134.5,132.6,131.3,128.5,127.7,125.8,127.4,126.5,125.8,120.9。
theoretical calculations and experimental results for the analysis of the product are as follows:
Anal.Calcd.For C14H10N2O：C,75.66；H,4.54；N,12.60；O,7.20。
Found：C,75.65；H,4.53；N,12.61；O,7.21。
example 2: synthesis of 2- (4-methylphenyl) quinazolinone
Starting material 2-aminobenzamide (0.3mmol, 1equiv), catalyst palladium trifluoroacetate (Pd (TFA)20.03mmol, 10%) and ligand 2, 2' -bipyridine (bpy, 0.06mmol, 20%) were added to a reaction vessel, the reaction vessel was continuously subjected to 3 times of air-oxygen charging operation, then the reaction solvent dimethylsulfoxide (DMSO, 0.4mL) and the raw material 4-methylstyrene (0.9mmol, 3equiv) were continuously added to the reaction vessel, followed by stirring in an oil bath at a reaction temperature of 100 ℃ until the reaction was completed (about 12 hours), then the reaction solvent was spun off, and column chromatography was performed (column packed with 300-400 mesh silica gel, volume ratio of dichloromethane to ethyl acetate was 10: eluent 1) was added, and after separation and purification, a white solid was obtained with a yield of 83%.
The data of the nuclear magnetic resonance hydrogen spectrum of the obtained product are as follows:
1H NMR(400MHz,DMSO-d6)12.45(1H,s),8.16(1H,dd),8.1(2H,d),7.80-7.84(1H,m),7.72(1H,d),7.48-7.52(1H,m),7.34(2H,d),2.38(3H,s)。
the data of the nuclear magnetic resonance carbon spectrum of the obtained product are as follows:
13C NMR(100MHz,DMSO-d6)δ:162.2,152.2,148.7,141.4,134.4,129.8,129.1,127.6,127.2,126.3,125.8,120.8,20.9。
theoretical calculations and experimental results for the analysis of the product are as follows:
Anal.Calcd.For C15H12N2O：C,76.25；H,5.12；N,11.86；O,6.77。
Found：C,76.24；H,5.11；N,11.85；O,6.76。
example 3: synthesis of 2- (4-fluorophenyl) quinazolinone
Starting material 2-aminobenzamide (0.3mmol, 1equiv), catalyst palladium trifluoroacetate (Pd (TFA)20.03mmol, 10%) and ligand 2, 2' -bipyridine (bpy, 0.06mmol, 20%) were added to a reaction vessel, the reaction vessel was continuously subjected to 3 times of air-oxygen charging operation, then the reaction solvent dimethylsulfoxide (DMSO, 0.4mL) and the raw material 4-fluorostyrene (0.9mmol, 3equiv) were continuously added to the reaction vessel, followed by stirring in an oil bath at a reaction temperature of 100 ℃ until the reaction was completed (about 12 hours), then the reaction solvent was spun off, and column chromatography was performed (column packed with 300-400 mesh silica gel, volume ratio of dichloromethane to ethyl acetate was 10: eluent 1) and then the white solid is obtained after separation and purification, and the yield is 78%.
The data of the nuclear magnetic resonance hydrogen spectrum of the obtained product are as follows:
1H NMR(400MHz,DMSO-d6)δ:12.55(s,1H),8.23-8.27(m,2H),8.15(1H,dd),7.81-7.85(1H,m),7.73(1H,d),7.50-7.54(1H,m),7.36-7.41(2H,m)。
the data of the nuclear magnetic resonance carbon spectrum of the obtained product are as follows:
13CNMR(100MHz,DMSO-d6)δ：165.2,162.7,151.3,148.5,134.5,130.3,129.1,127.3,126.5,125.8,120.8,115.5。
theoretical calculations and experimental results for the analysis of the product are as follows:
Anal.Calcd.For C14H9FN2O：C,69.99；H,3.78；F,7.91；N,11.66；O,6.66。
Found：C,69.98；H,3.77；F,7.90；N,11.65；O,6.65。
example 4: synthesis of 2- (4-chlorophenyl) quinazolinone
Starting material 2-aminobenzamide (0.3mmol, 1equiv), catalyst palladium trifluoroacetate (Pd (TFA)20.03mmol, 10%) and ligand 2, 2' -bipyridine (bpy, 0.06mmol, 20%) were added to a reaction vessel, the reaction vessel was continuously subjected to 3 times of air-oxygen charging operation, then the reaction solvent dimethylsulfoxide (DMSO, 0.4mL) and the raw material 4-chlorostyrene (0.9mmol, 3equiv) were continuously added to the reaction vessel, followed by stirring in an oil bath at a reaction temperature of 100 ℃ until the reaction was completed (about 12 hours), then the reaction solvent was spun off, and column chromatography was performed (column packed with 300-400 mesh silica gel, volume ratio of dichloromethane to ethyl acetate was 10: eluent 1) and then the white solid is obtained after separation and purification, and the yield is 76%.
The data of the nuclear magnetic resonance hydrogen spectrum of the obtained product are as follows:
1H NMR(400MHz,DMSO-d6)δ：12.6(1H,s),7.35–7.43(1H,m),7.54–7.60(1H,m),7.64–7.69(2H,m),8.18–8.27(2H,m)。
the data of the nuclear magnetic resonance carbon spectrum of the obtained product are as follows:
13C NMR(100MHz,DMSO-d6)δ：159.9,143.7,138.7,133.5,131.6,131.4,130.7,130.4,128.9,128.5,127.3,127.2,124.9,123.8,123.2,122.3,122.0。
theoretical calculations and experimental results for the analysis of the product are as follows:
Anal.Calcd.For C14H9ClN2O：C,65.51；H,3.53；Cl,13.81；N,10.91；O,6.23。
Found：C,65.50；H,3.52；Cl,13.80；N,10.90；O,6.22。
example 5: synthesis of 2- (4-bromophenyl) quinazolinone
Starting material 2-aminobenzamide (0.3mmol, 1equiv), catalyst palladium trifluoroacetate (Pd (TFA)20.03mmol, 10%) and ligand 2, 2' -bipyridine (bpy, 0.06mmol, 20%) were added to a reaction vessel, the reaction vessel was continuously subjected to 3 times of air-oxygen charging operation, then the reaction solvent dimethylsulfoxide (DMSO, 0.4mL) and the raw material 4-bromostyrene (0.9mmol, 3equiv) were continuously added to the reaction vessel, followed by stirring in an oil bath at a reaction temperature of 100 ℃ until the reaction was completed (about 12 hours), then the reaction solvent was spun off, and column chromatography was performed (the column was filled with 300-400 mesh silica gel, the volume ratio of dichloromethane to ethyl acetate was 10: eluent 1) and then the white solid is obtained after separation and purification, and the yield is 70%.
The data of the nuclear magnetic resonance hydrogen spectrum of the obtained product are as follows:
1H NMR(400MHz,DMSO-d6)δ：12.56(1H,s),8.12-8.19(3H,m),7.84(1H,t),7.73-7.77(2H,m),7.50-7.59(2H,m)。
the data of the nuclear magnetic resonance carbon spectrum of the obtained product are as follows:
13C NMR(100MHz,DMSO-d6)δ：162.1,151.4,148.4,134.5,131.5,131.3,129.7,127.7,126.5,125.8,125.1,120.9。
theoretical calculations and experimental results for the analysis of the product are as follows:
Anal.Calcd.For C14H9BrN2O:C,55.84；H,3.01；Br,26.53；N,9.30；O,5.31。
Found：C,55.84；H,3.01；Br,26.53；N,9.30；O,5.31。
example 6: synthesis of 6- (4-nitrophenyl) quinazolinone
Starting material 2-aminobenzamide (0.3mmol, 1equiv), catalyst palladium trifluoroacetate (Pd (TFA)20.03mmol, 10%) and ligand 2, 2' -bipyridine (bpy, 0.06mmol, 20%) were added to a reaction vessel, the reaction vessel was continuously subjected to 3 times of air-oxygen charging operation, then the reaction solvent dimethylsulfoxide (DMSO, 0.4mL) and the raw material 4-nitrostyrene (0.9mmol, 3equiv) were continuously added to the reaction vessel, followed by stirring in an oil bath at a reaction temperature of 100 ℃ until the reaction was completed (about 12 hours), then the reaction solvent was spun off, and column chromatography was performed (column packed with 300-400 mesh silica gel, volume ratio of dichloromethane to ethyl acetate was 10: eluent 1) and obtaining white solid with the yield of 58 percent after separation and purification.
The data of the nuclear magnetic resonance hydrogen spectrum of the obtained product are as follows:
1H NMR(400MHz,DMSO-d6)δ:12.83(1H,s),8.37-8.43(m,4H),8.18(d,J＝8.2Hz,1H),7.88(t,J＝7.9Hz,1H),7.67(d,J＝7.2Hz,1H),7.58(t,J＝8.0Hz,1H)。
the data of the nuclear magnetic resonance carbon spectrum of the obtained product are as follows:
13CNMR(100MHz,DMSO-d6)δ:115.5,115.8,118.4,124.5,128.3,128.9,134.5,148.2,148.3,150.3,164.3(CO)。
theoretical calculations and experimental results for the analysis of the product are as follows:
Anal.Calcd.For C14H9N3O3：C,62.92；H,3.39；N,15.72；O,17.96。
Found：C,62.91；H,3.38；N,15.71；O,17.95。
example 7: synthesis of 2- (4-trifluoromethylphenyl) quinazolinone
Starting material 2-aminobenzamide (0.3mmol, 1equiv), catalyst palladium trifluoroacetate (Pd (TFA)2，0.03mmol，10%) and ligand 2, 2' -bipyridine (bpy, 0.06mmol, 20%) were added to a reaction vessel, the reaction vessel was continuously subjected to 3 pump-oxygen operations, then the reaction solvent dimethylsulfoxide (DMSO, 0.4mL) and the starting material 4-trifluoromethylstyrene (0.9mmol, 3equiv) were continuously added to the reaction vessel, followed by stirring in an oil bath at a reaction temperature of 100 ℃ until the reaction was completed (about 12h), then the reaction solvent was spun off, and the mixture was purified by column chromatography (column packed with 300-400 mesh silica gel, in a volume ratio of dichloromethane to ethyl acetate of 10: eluent 1) and obtaining white solid with the yield of 60 percent after separation and purification.
The data of the nuclear magnetic resonance hydrogen spectrum of the obtained product are as follows:
1H NMR(400MHz,DMSO-d6)δ：12.8(1H,s),8.39–8.42(2H,m),7.80–7.98(4H,m),8.19–8.23(1H,m),7.57–7.63(1H,m)。
the data of the nuclear magnetic resonance carbon spectrum of the obtained product are as follows:
13C NMR(100MHz,DMSO-d6)δ：122.2,123.0,126.4,126.9,128.1,128.6,129.7,131.8,135.7,137.5,149.3,152.2,163.1。
theoretical calculations and experimental results for the analysis of the product are as follows:
Anal.Calcd.For C15H9F3N2O：C,62.07；H,3.13；F,19.64；N,9.65；O,5.51。
Found：C,62.06；H,3.12；F,19.63；N,9.64；O,5.50。
example 8: synthesis of 2- (4-methoxyphenyl) quinazolinone
Starting material 2-aminobenzamide (0.3mmol, 1equiv), catalyst palladium trifluoroacetate (Pd (TFA)20.03mmol, 10%) and ligand 2, 2' -bipyridine (bpy, 0.06mmol, 20%) were added to a reaction vessel, the reaction vessel was subjected to 3 consecutive pump-oxygen operations, and then the reaction solvent dimethylsulfoxide (DMSO,0.4mL) and 4-methoxystyrene (0.9mmol, 3equiv) as a starting material, followed by stirring in an oil bath at a reaction temperature of 100 ℃ until the reaction is completed (about 12 hours), then removing the reaction solvent by spinning off, and purifying by column chromatography (column packed with 300-400 mesh silica gel, in a volume ratio of dichloromethane to ethyl acetate of 10: eluent 1) and then the white solid is obtained after separation and purification, and the yield is 79%.
The data of the nuclear magnetic resonance hydrogen spectrum of the obtained product are as follows:
1H NMR(400MHz,DMSO-d6)δ:12.39(1H,s),8.21-8.17(2H,m),8.13(1H,dd),7.79-7.83(1H,m),7.69-7.71(1H,m),7.46-7.50(1H,m),7.07-7.11(2H,m),3.85(3H,s)。
the data of the nuclear magnetic resonance carbon spectrum of the obtained product are as follows:
13C NMR(100MHz,DMSO-d6)δ:162.2,161.8,151.8,148.7,134.4,129.4,127.2,126.0,125.7,124.7,120.6,113.9,55.4。
theoretical calculations and experimental results for the analysis of the product are as follows:
Anal.Calcd.For C15H12N2O2：C,71.42；H,4.79；N,11.10；O,12.68。
Found：C,71.41；H,4.78；N,11.11；O,12.67。
example 9 to example 24: using different reaction solvents
Examples 9 to 24 were identical to example 1 except that the reaction solvent used was different, and the reaction solvents used in the respective examples and the yields of the respective products were as shown in the following table:
as can be seen from the above table, when a solvent other than dimethylsulfoxide is used, for example: polar solvents 3-dimethyl-2-imidazolidinone, N-dimethylacetamide and tetrahydrofuran all react, but the yield is significantly reduced compared with dimethyl sulfoxide, which means that the yield of the reaction is significantly influenced by the appropriate choice of the solvent.
Example 25 to example 30: using different palladium catalysts
Examples 25 to 30 were identical to example 1 except that the palladium catalyst was different, and the yields of the palladium catalyst and the corresponding products used in each example are shown in the following table:
| numbering | Palladium catalyst | Reaction yield |
| Example 25 | Palladium acetate | 64％ |
| Example 26 | Palladium chloride | 0 |
| Example 27 | Palladium bromide | 0 |
| Example 28 | Allyl palladium chloride | 0 |
| Example 29 | Palladium acetylacetonate | 0 |
| Example 30 | Bis (dibenzylideneacetone) palladium | 0 |
As can be seen from the above table, when a palladium catalyst other than palladium trifluoroacetate is used, for example: the palladium catalyst, palladium acetate, also reacted, but in significantly lower yields compared to palladium trifluoroacetate, indicating that the appropriate choice of palladium catalyst has a significant effect on the yield of the reaction.
Example 31 to example 39: using different ligands
The same operations as in example 1 were carried out except that the ligands were different in examples 31 to 39, and the yields of the ligands and the corresponding products used in the respective examples are shown in the following table:
| numbering | Ligands | Reaction yield |
| Example 31 | 4, 4 '-dimethyl-2, 2' -bipyridine | 67％ |
| Example 32 | 5, 5 '-dimethyl-2, 2' -bipyridine | 38％ |
| Example 33 | 6, 6 '-dimethyl-2, 2' -bipyridine | 0 |
| Example 34 | 1, 10-phenanthroline | 48％ |
| Example 35 | 4, 7-phenyl-1, 10-phenanthroline | 35％ |
| Example 36 | Tetramethyl guanidine | 0 |
| Example 37 | Tetramethyl ethylene diamine | 0 |
| Example 38 | Dimethyl ethylenediamine | 0 |
| Example 39 | Triphenylphosphine | 0 |
As can be seen from the above table, when ligands other than 2, 2' -bipyridine are used, such as: the bidentate nitrogen ligand 5, 5 ' -bipyridyl, 6 ' -bipyridyl, 1, 10-phenanthroline and 4, 7-phenyl-1, 10-phenanthroline can react, but the yield is obviously reduced compared with that of 2,2 ' -bipyridyl, which shows that the yield of the reaction is obviously influenced by proper selection of the ligand.
Example 40 to example 43: difference in reaction temperature
Examples 40 to 43 were identical to example 1 except for the difference in reaction temperature, and the reaction temperature and the yield of the corresponding product used in each example are shown in the following table:
| numbering | Reaction temperature | Reaction yield |
| Example 40 | 40℃ | 0 |
| EXAMPLE 41 | 60℃ | 0 |
| Example 42 | 80℃ | 60％ |
| Example 43 | 110℃ | 71％ |
As can be seen from the above table, when temperatures other than 100 ℃ are used, such as: both 80 ℃ and 110 ℃ were able to react, but the yield was significantly reduced compared to 100 ℃, indicating that the appropriate choice of temperature had a significant effect on the yield of the reaction.
In conclusion, the invention uses cheap and easily available styrene compounds as raw materials, has simple operation, easy post-treatment and short reaction time, and provides a brand new synthetic route for the efficient and rapid synthesis of the 2-phenylquinazolinone compounds.
It should be noted that the above-mentioned embodiments do not limit the present invention in any way, and all technical solutions obtained by using equivalent alternatives or equivalent variations fall within the protection scope of the present invention.
Claims (5)
1. The method for synthesizing the 2-phenylquinazolinone compound is characterized in that a styrene compound and 2-aminobenzamide are used as reaction raw materials, under the combined action of a palladium catalyst, a ligand and oxygen, carbon-carbon bonds of the styrene compound are broken to generate a benzaldehyde compound, and the generated benzaldehyde compound and the 2-aminobenzamide are subjected to intermolecular condensation coupling reaction to obtain the 2-phenylquinazolinone compound, wherein the reaction temperature is 80-110 ℃, and the reaction equation is as follows:
in the formula, R is hydrogen, fluorine, chlorine, bromine, methyl, trifluoromethyl, nitryl or methoxyl;
the reaction solvent is at least one of 3-dimethyl-2-imidazolidinone, dimethyl sulfoxide, tetrahydrofuran and N, N-dimethylacetamide;
the palladium catalyst is palladium acetate or palladium trifluoroacetate;
the ligand is at least one of 2,2 ' -bipyridyl, 4 ' -dimethyl-2, 2 ' -bipyridyl, 5 ' -dimethyl-2, 2 ' -bipyridyl, 1, 10-phenanthroline and 4, 7-diphenyl-1, 10-phenanthroline.
2. The method for synthesizing 2-phenylquinazolinone compounds according to claim 1, comprising the following steps:
step 1: adding 2-aminobenzamide, a palladium catalyst and a ligand into a reaction vessel, and then continuously performing air extraction-oxygen filling operation on the reaction vessel for 3 times;
step 2: continuously adding a styrene compound and a reaction solvent into the reaction vessel, and reacting at the reaction temperature of 80-110 ℃ until the reaction is finished;
step 3: and separating and purifying the mixture obtained by the reaction.
3. The method for synthesizing the 2-phenylquinazolinone compound according to claim 1, wherein the molar ratio of the 2-aminobenzamide to the styrene compound is 1: 1-1: 3.
4. The method for synthesizing the 2-phenylquinazolinone compound according to claim 1, wherein the molar ratio of the palladium catalyst to the 2-aminobenzamide is 1: 10-1: 100.
5. The method for synthesizing the 2-phenylquinazolinone compound according to claim 1, wherein the molar ratio of the ligand to the 2-aminobenzamide is 1: 5-1: 100.
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