CN113563272A - Preparation method of 2-phenylquinazolinone compound - Google Patents
Preparation method of 2-phenylquinazolinone compound Download PDFInfo
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- CN113563272A CN113563272A CN202110910293.7A CN202110910293A CN113563272A CN 113563272 A CN113563272 A CN 113563272A CN 202110910293 A CN202110910293 A CN 202110910293A CN 113563272 A CN113563272 A CN 113563272A
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- phenylquinazolinone
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- ethyl acetate
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 13
- 238000002360 preparation method Methods 0.000 title claims abstract description 7
- 238000006243 chemical reaction Methods 0.000 claims abstract description 29
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000011630 iodine Substances 0.000 claims abstract description 21
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 21
- -1 2- (benzylamino) benzamide compound Chemical class 0.000 claims abstract description 17
- 239000003054 catalyst Substances 0.000 claims abstract description 10
- 238000000034 method Methods 0.000 claims abstract description 10
- 239000002904 solvent Substances 0.000 claims abstract description 8
- DOFHLSHJNOHLFW-UHFFFAOYSA-N 2-(benzylamino)benzamide Chemical compound NC(=O)C1=CC=CC=C1NCC1=CC=CC=C1 DOFHLSHJNOHLFW-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 108
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 44
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 38
- 238000004440 column chromatography Methods 0.000 claims description 18
- 239000012074 organic phase Substances 0.000 claims description 18
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 2
- 229960001701 chloroform Drugs 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 20
- 230000015572 biosynthetic process Effects 0.000 abstract description 19
- 239000002994 raw material Substances 0.000 abstract description 7
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 62
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 16
- 238000005160 1H NMR spectroscopy Methods 0.000 description 16
- 239000003208 petroleum Substances 0.000 description 16
- 239000012295 chemical reaction liquid Substances 0.000 description 11
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 7
- 238000000926 separation method Methods 0.000 description 7
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 3
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 description 3
- 238000004293 19F NMR spectroscopy Methods 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 3
- ZLGVZKQXZYQJSM-UHFFFAOYSA-N 1,2-diphenylbenzimidazole Chemical compound C1=CC=CC=C1C1=NC2=CC=CC=C2N1C1=CC=CC=C1 ZLGVZKQXZYQJSM-UHFFFAOYSA-N 0.000 description 2
- AVRPFRMDMNDIDH-UHFFFAOYSA-N 1h-quinazolin-2-one Chemical class C1=CC=CC2=NC(O)=NC=C21 AVRPFRMDMNDIDH-UHFFFAOYSA-N 0.000 description 2
- DPEOPHOCJXTCHK-UHFFFAOYSA-N 2-(2,5-difluorophenyl)-3H-quinazolin-4-one Chemical compound FC1=C(C=C(C=C1)F)C1=NC2=CC=CC=C2C(N1)=O DPEOPHOCJXTCHK-UHFFFAOYSA-N 0.000 description 2
- GGOWAPMNHOQUBZ-UHFFFAOYSA-N 2-(3,5-dimethoxyphenyl)-1h-quinazolin-4-one Chemical compound COC1=CC(OC)=CC(C=2NC3=CC=CC=C3C(=O)N=2)=C1 GGOWAPMNHOQUBZ-UHFFFAOYSA-N 0.000 description 2
- RNDLJEZKSAHWAC-UHFFFAOYSA-N 2-(3,5-dimethylphenyl)-3H-quinazolin-4-one Chemical compound CC=1C=C(C=C(C=1)C)C1=NC2=CC=CC=C2C(N1)=O RNDLJEZKSAHWAC-UHFFFAOYSA-N 0.000 description 2
- DUQSFLFKFAGWIS-UHFFFAOYSA-N 2-(3-methoxyphenyl)-1h-quinazolin-4-one Chemical compound COC1=CC=CC(C=2NC3=CC=CC=C3C(=O)N=2)=C1 DUQSFLFKFAGWIS-UHFFFAOYSA-N 0.000 description 2
- UTEHUKGJDLVHIH-UHFFFAOYSA-N 2-(4-methylphenyl)-1h-quinazolin-4-one Chemical compound C1=CC(C)=CC=C1C1=NC(=O)C2=CC=CC=C2N1 UTEHUKGJDLVHIH-UHFFFAOYSA-N 0.000 description 2
- PXBFMLJZNCDSMP-UHFFFAOYSA-N 2-Aminobenzamide Chemical compound NC(=O)C1=CC=CC=C1N PXBFMLJZNCDSMP-UHFFFAOYSA-N 0.000 description 2
- PQPIYBZADFPOKZ-UHFFFAOYSA-N 2-[4-(trifluoromethoxy)phenyl]-1h-quinazolin-4-one Chemical compound C1=CC(OC(F)(F)F)=CC=C1C1=NC(=O)C2=CC=CC=C2N1 PQPIYBZADFPOKZ-UHFFFAOYSA-N 0.000 description 2
- 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 2
- FPQXJSZKSFDUFR-UHFFFAOYSA-N 3-methyl-2-phenylquinazolin-4-one Chemical compound N=1C2=CC=CC=C2C(=O)N(C)C=1C1=CC=CC=C1 FPQXJSZKSFDUFR-UHFFFAOYSA-N 0.000 description 2
- QNEIILVTYYDCIF-UHFFFAOYSA-N 5-fluoro-2-phenyl-1h-quinazolin-4-one Chemical compound N=1C(=O)C=2C(F)=CC=CC=2NC=1C1=CC=CC=C1 QNEIILVTYYDCIF-UHFFFAOYSA-N 0.000 description 2
- OGVYLCTUZFHCOU-UHFFFAOYSA-N 5h-quinazolin-6-one Chemical compound N1=CN=C2C=CC(=O)CC2=C1 OGVYLCTUZFHCOU-UHFFFAOYSA-N 0.000 description 2
- PGMBDCKPRFLKLG-UHFFFAOYSA-N 6-chloro-2-phenyl-1h-quinazolin-4-one Chemical compound N=1C(=O)C2=CC(Cl)=CC=C2NC=1C1=CC=CC=C1 PGMBDCKPRFLKLG-UHFFFAOYSA-N 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- AKLQKSHYAAAFEV-UHFFFAOYSA-N 2-(3,4-dihydro-1H-isoquinolin-2-yl)-4-methylbenzamide Chemical compound CC1=CC=C(C(N)=O)C(N2CC3=CC=CC=C3CC2)=C1 AKLQKSHYAAAFEV-UHFFFAOYSA-N 0.000 description 1
- PSQHWKOGHVLUOB-UHFFFAOYSA-N 2-(3,5-dimethylphenyl)-3-methylquinazolin-4-one Chemical compound CC1=CC(C(N2C)=NC3=CC=CC=C3C2=O)=CC(C)=C1 PSQHWKOGHVLUOB-UHFFFAOYSA-N 0.000 description 1
- IXMXCFSRQIHRHB-UHFFFAOYSA-N 2-(4-fluorophenyl)-1h-quinazolin-4-one Chemical compound C1=CC(F)=CC=C1C1=NC(=O)C2=CC=CC=C2N1 IXMXCFSRQIHRHB-UHFFFAOYSA-N 0.000 description 1
- IZGKXIYZQMMXLP-UHFFFAOYSA-N 2-(benzylamino)-N-methylbenzamide Chemical compound CNC(=O)C1=CC=CC=C1NCC1=CC=CC=C1 IZGKXIYZQMMXLP-UHFFFAOYSA-N 0.000 description 1
- XXUNIGZDNWWYED-UHFFFAOYSA-N 2-methylbenzamide Chemical compound CC1=CC=CC=C1C(N)=O XXUNIGZDNWWYED-UHFFFAOYSA-N 0.000 description 1
- SOYJZZYSQMMFFC-UHFFFAOYSA-N 3-methyl-2-(4-methylphenyl)quinazolin-4-one Chemical compound C1=CC(C)=CC=C1C1=NC2=CC=CC=C2C(=O)N1C SOYJZZYSQMMFFC-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 230000002365 anti-tubercular Effects 0.000 description 1
- 230000002155 anti-virotic effect Effects 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/18—Benzimidazoles; Hydrogenated benzimidazoles with aryl radicals directly attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
Abstract
The invention relates to a preparation method of 2-phenyl quinazolinone compounds, and the specific structure is shown as II. The method comprises the steps of taking a 2- (benzylamino) benzamide compound (I) as a raw material for an experimental model reaction, adding an elemental iodine catalyst and a solvent into a reaction reagent, and obtaining a target product (II); the innovation point of the invention is that the 2- (benzylamino) benzamide which is easy to obtain is taken as the raw material for the first time, a metal-free catalyst is used under mild conditions, the 2-phenylquinazolinone compound is obtained with high yield, and the invention has the advantages of green synthesis such as step economy, atom economy and the like.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a 2-phenylquinazolinone compound and a preparation method thereof.
Background
Quinazolinone compounds are nitrogen-containing benzo heterocyclic compounds, and belong to a large class of alkaloids. Has wide application in the fields of pesticide, medicine and the like, and has prominent effect in the fields of antibiosis, antivirus, antidiabetic and antituberculosis, in particular in the research field of antitumor drugs. In conventional methods, quinazolinones are typically formed by coupling 2-aminobenzamide with aldehydes, carboxylic acids, and carboxyl halides. The innovation point of the method is that the 2- (benzylamino) benzamide which is easy to obtain is used as a raw material for the first time, a metal-free catalyst is used under mild conditions, and the 2-phenylquinazolinone compound is obtained with high yield, so that the method has the advantages of green synthesis such as step economy, atom economy and the like.
Disclosure of Invention
Based on the technical problems, the technical scheme of the invention provides a synthesis scheme of a 2-phenylquinazolinone compound, wherein the structure of the 2-phenylquinazolinone compound is shown as a formula (II):
said R1Including hydrogen, C1-C3 alkyl, C1-C3 alkyloxy, C3-C7 cycloalkyl, C1-C3 alkylamino
Any one of alkyl halide, halogen hydroxyl, amino, nitro, cyano and aryl;
said R2Comprises any one of hydrogen, C1-C3 alkyl, C1-C3 alkyloxy, halogenated alkyl, C3-C7 naphthenic base, C1-C3 alkylamino and aryl;
said R3Comprises any one of hydrogen, C1-C3 alkyl, C1-C3 alkyloxy, halogenated alkyl, C3-C7 naphthenic base, C1-C3 alkylamino and aryl.
Based on the structural formula provided above, the technical scheme of the invention further preferably obtains the 2-phenylquinazoline-4 (3H) -ketone compound which comprises
The technical scheme of the invention also comprises a preparation method of the 2-phenyl quinazolinone compound, the method takes 2- (benzylamino) benzamide as a raw material, DMSO as a solvent, iodine simple substance as a catalyst, the reaction is carried out for 0.1-12h (the reaction temperature is further preferably 130 ℃, the reaction time is 6h) at 50-150 ℃, after the reaction is finished, ethyl acetate is extracted, organic phase is combined and concentrated, and column chromatography separation is carried out to obtain a target product (II), and the specific reaction equation is as follows:
2- (benzylamino) benzamide (I), and the molar ratio of the materials of the catalyst is 1-2: 0.1-0.5.
The catalyst comprises elemental iodine.
The solvent comprises a single solvent of dichloromethane, trichloromethane, toluene, ethyl acetate, diethyl ether, 1, 4-dioxane, 1, 2-dichloroethane, acetonitrile, ethylene glycol dimethyl ether, methyl tert-butyl ether, tetrahydrofuran, N-dimethylformamide and dimethyl sulfoxide, and is further optimized as follows: dimethyl sulfoxide (DMSO).
The invention discloses a 2- (benzylamino) benzamide compound and a preparation method thereof. The method takes a 2- (benzylamino) benzamide compound (I) as a raw material for the experimental model reaction, takes dimethyl sulfoxide as a solvent, and performs an oxidation addition reaction under the action of a catalytic amount of a simple substance iodine to directly obtain a target product (II). The method uses the 2- (benzylamino) benzamide (I) as a raw material for the first time, is simple and convenient to operate, easy to obtain the raw material, mild in reaction condition, high in yield and wide in application prospect.
Detailed Description
The present invention will be further described with reference to the following examples, but the present invention is not limited to the following examples.
EXAMPLE 1 Synthesis of 2-phenylquinazolin-4 (3H) -one
2- (benzylamino) benzamide (0.44mmol,100mg), elemental iodine (0.04mmol,11mg) and dimethyl sulfoxide (2ml) are sequentially added into a test tube and reacted at 130 ℃ for 6H, after that, the reaction solution is extracted by ethyl acetate for 3 times, the combined organic phases are concentrated to dryness and separated by column chromatography (petroleum ether: ethyl acetate 4:1) to obtain 2-phenylquinazolin-4 (3H) -one with the yield of (91mg, 91%).1H NMR(400MHz,DMSO-d6):δ＝ 12.54(s,1H),8.21-8.15(m,3H),7.88-7.82(m,1H),7.76(d,J＝7.2Hz,1H),7.62-7.51(m,4H)；13C NMR(100 MHz,DMSO-d6):δ＝162.71,152.78,149.19,135.09,133.16,131.88,129.08,128.23,127.97,127.07,126.32, 121.43.
The catalyst and the dosage are replaced, the reaction time and the reaction solvent are changed, and when the reaction temperature is changed, the reaction result is as follows:
EXAMPLE 2 Synthesis of 5-fluoro-2-phenylquinazolin-4 (3H) -one
2- (benzylamino) -6-fluorobenzamide (0.41mmol,100mg), elemental iodine (0.04mmol,11mg) and dimethyl sulfoxide (2ml) are sequentially added into a test tube and reacted at 130 ℃ for 6H, after the reaction is finished, the reaction liquid is extracted 3 times by ethyl acetate, the organic phases are combined and concentrated to dryness, and the mixture is separated by column chromatography (petroleum ether: ethyl acetate 4:1) to obtain 5-fluoro-2-phenylquinazolin-4 (3H) -one, wherein the yield is (89mg, 77%).1H NMR(400MHz,DMSO-d6): δ＝12.59(s,1H),8.20-8.17(m,2H),7.83-7.78(m,1H),7.61-7.54(m,4H),7.26-7.25(m,1H)；13C NMR(100 MHz,DMSO-d6):δ＝162.29,160.0,159.68,153.73,151.32,135.60(d,J＝10.7Hz),132.67,132.13,129.80(d,J ＝75.6Hz),124.02,113.33(d,J＝20.20Hz),110.86(d,J＝6.1Hz).19F NMR(376MHz,DMSO-d6)δ＝111.45.
EXAMPLE 3 Synthesis of 6-chloro-2-phenylquinazolin-4 (3H) -one
2- (benzylamino) -5-chlorobenzamide (0.38mmol,100mg), elemental iodine (0.04mmol,11mg) and dimethyl sulfoxide (2ml) are sequentially added into a test tube and reacted at 130 ℃ for 6H, after that, the reaction solution is extracted for 3 times by ethyl acetate, the combined organic phases are concentrated to dryness and separated by column chromatography (petroleum ether: ethyl acetate 4:1) to obtain 6-chloro-2-phenylquinazolin-4 (3H) -one, and the yield is (82mg, 84%).1H NMR(400MHz,DMSO-d6): δ＝12.76(s,1H),8.19(d,J＝7.2,2H),8.10(d,J＝2.4,1H),7.90-7.87(m,1H),7.78(d,J＝8.4Hz,1H), 7.64-7.55(m,3H)；13C NMR(100MHz,DMSO-d6):δ＝161.85,153.38,147.91,135.16,132.95,132.07,131.22, 130.15,129.11,128.32,125.35,122.69.
EXAMPLE 4 Synthesis of 2- (4-fluorophenyl) quinazolin-4 (3H) -one
2- (4-fluorobenzyl) aminobenzamide (0.40mmol,100mg), elemental iodine (0.04mmol,11mg) and dimethyl sulfoxide (2ml) are sequentially added into a test tube and reacted at 130 ℃ for 6H, after reaction, the reaction liquid is extracted for 3 times by ethyl acetate, organic phases are combined and concentrated to dryness, and column chromatography (petroleum ether: ethyl acetate 4:1) is carried out for separation to obtain 2- (4-fluorophenyl) quinazoline-4 (3H) -ketone, wherein the yield is (84mg, 85%).1H NMR(400MHz, DMSO-d6):δ＝12.60(s,1H),8.30-8.25(m,2H),8.17(dd,J1＝8.0Hz,J2＝1.6Hz,1H),7.88-7.84(m,1H),7.75 (dd,J1＝8.0Hz,J2＝1.2Hz,1H),7.56-7.52(m,1H),7.41(t,J＝8.8Hz,2H)；13C NMR(100MHz,DMSO-d6):δ＝162.67,150.47(d,J＝20.20Hz),135.11,130.89,130.79,129.71,127.94,127.09,126.32,121.35,116.21, 115.99.
EXAMPLE 5 Synthesis of 2- (2, 5-difluorophenyl) quinazolin-4 (3H) -one
2- (2, 5-difluorobenzyl) aminobenzamide (0.38mmol,100mg), elemental iodine (0.04mmol,11mg) and dimethyl sulfoxide (2ml) are sequentially added into a test tube and reacted at 130 ℃ for 6H, after that, the reaction solution is extracted for 3 times by ethyl acetate, the organic phases are combined and concentrated to dryness, and the mixture is separated by column chromatography (petroleum ether: ethyl acetate 4:1) to obtain 2- (2, 5-difluorophenyl) quinazolin-4 (3H) -one with the yield of (85mg, 86%).1H NMR(400MHz, DMSO-d6):δ＝12.67(s,1H),8.19(dd,J1＝8.0Hz,J2＝1.2Hz,1H),7.90-7.86(m,1H),7.76(d,J＝8.0Hz,1H), 7.70-7.58(m,2H),7.52-7.47(m,2H)；13C NMR(100MHz,DMSO-d6):δ＝161.88,159.00,157.23(d,J＝45.3Hz), 155.00,149.01(d,J＝32.7Hz),135.15,128.03,127.75,126.34,121.67,119.91(d,J＝8.8Hz),119.67(d,J＝8.9 Hz),118.49(dd,J1＝24.4Hz,J2＝8.9Hz),117.82(dd,J1＝25.8Hz,J2＝2.8Hz)；19F NMR(376MHz,DMSO-d6) δ＝120.03,118.14.
EXAMPLE 6 Synthesis of 2- (3-methoxyphenyl) quinazolin-4 (3H) -one
2- (3-methoxybenzyl) aminobenzamide (0.38mmol,100mg), elemental iodine (0.04mmol,11mg) and dimethyl sulfoxide (2ml) are sequentially added into a test tube and reacted at 130 ℃ for 6H, after reaction, the reaction liquid is extracted for 3 times by ethyl acetate, organic phases are combined and concentrated to dryness, and column chromatography (petroleum ether: ethyl acetate 4:1) is carried out for separation to obtain 2- (3-methoxyphenyl) quinazolin-4 (3H) -one, wherein the yield is (90mg, 91%).1H NMR(400MHz, DMSO-d6):δ＝12.57(s,1H),8.17(dd,J1＝8.0Hz,J2＝1.6Hz,1H),7.90-7.73(m,4H),7.61-7.43(m,2H),7.17 (ddd,J1＝8.0Hz,J1＝3.2Hz,J3＝0.8Hz,1H),3.88(s,3H)；13C NMR(100MHz,DMSO-d6):δ＝162.72,159.80, 152.51,135.11,134.48,130.23,128.01,127.12,126.33,121.47,120.59,118.08,112.97,55.85.
EXAMPLE 7 Synthesis of 2- (3, 5-dimethoxyphenyl) quinazolin-4 (3H) -one
2- (3, 5-dimethoxybenzyl) aminobenzamide (0.35mmol,100mg), elemental iodine (0.04mmol,11mg) and dimethyl sulfoxide (2ml) are sequentially added into a test tube and reacted at 130 ℃ for 6H, after that, the reaction solution is extracted for 3 times by ethyl acetate, the organic phases are combined and concentrated to dryness, and the mixture is separated by column chromatography (petroleum ether: ethyl acetate 4:1) to obtain 2- (3, 5-dimethoxyphenyl) quinazolin-4 (3H) -one, wherein the yield is (84mg, 85%).1H NMR (400MHz,DMSO-d6):δ＝12.54(s,1H),8.17(dd,J1＝8.0Hz,J2＝1.2Hz,1H),7.87-7.73(m,2H),7.55-7.51(m, 1H),7.40(d,J＝2.4Hz,2H),6.71(t,J＝2.0Hz,1H),3.85(s,6H)；13C NMR(100MHz,DMSO-d6):δ＝162.69, 160.94,160.94,152.28,135.07,134.99,128.03,127.12,126.31,121.50,105.92,104.22,55.99.
EXAMPLE 8 Synthesis of 2- (4- (trifluoromethoxy) phenyl) quinazolin-4 (3H) -one
2- ((4- (trifluoromethoxy) benzyl) amino) benzamide (0.32mmol,100mg), elemental iodine (0.03mmol,8mg) and dimethyl sulfoxide (2ml) are sequentially added into a test tube and reacted at 130 ℃ for 6H, after the reaction is finished, the reaction liquid is extracted by ethyl acetate for 3 times, organic phases are combined and concentrated to be dry, and the 2- (4- (trifluoromethoxy) phenyl) quinazolin-4 (3H) -one is obtained by column chromatography (petroleum ether: ethyl acetate: 4:1), wherein the yield is (77mg, 78%).1H NMR(400MHz,DMSO-d6):δ＝12.68(s,1H),8.32(d,J＝8.8Hz,2H),8.18(dd,J1＝8.0Hz,J2＝1.6Hz,1H), 7.89-7.85(m,1H),7.77(dd,J1＝8.4Hz,J2＝1.2Hz,1H),7.60-7.52(m,3H)；13C NMR(100MHz,DMSO-d6):δ＝173.01,151.73,138.64,135.16,130.58,130.11,127.95,127.31,126.35,121.46,121.36,113.24,92.57.
EXAMPLE 9 Synthesis of 2- (p-tolyl) quinazolin-4 (3H) -one
2- ((4-methylbenzyl) amino) benzamide (0.42mmol,100mg), elemental iodine (0.04mmol,11mg) and dimethyl sulfoxide (2ml) are sequentially added into a test tube and reacted at 130 ℃ for 6 hours, after reaction, the reaction liquid is extracted for 3 times by ethyl acetate, organic phases are combined and concentrated to dryness, and separation is carried out by column chromatography (petroleum ether: ethyl acetate 4:1) to obtain 2- (p-tolyl) quinazolin-4 (3H) -one, wherein the yield is (67mg, 68%).1H NMR(400MHz, DMSO-d6):δ＝12.50(s,1H),8.17-8.10(m,3H),7.87-7.83(m,1H),7.74(d,J＝8.4Hz,1H),7.55-7.49(m,1H), 7.37(d,J＝8.0Hz,2H),2.41(s,3H)；13C NMR(100MHz,DMSO-d6):δ＝162.73,152.68,149.28,141.94, 135.07,130.33,129.67,128.14,127.88,126.89,126.30,121.34,21.47.
EXAMPLE 10 Synthesis of 2- (3, 5-dimethylphenyl) quinazolin-4 (3H) -one
2- ((3, 5-dimethylbenzyl) amino) benzamide (0.39mmol,100mg), elemental iodine (0.04mmol,11mg) and dimethyl sulfoxide (2ml) are sequentially added into a test tube and reacted at 130 ℃ for 6 hours, after the reaction is finished, the reaction liquid is extracted by ethyl acetate for 3 times, organic phases are combined and concentrated to be dry, and the 2- (3, 5-dimethylphenyl) quinazolin-4 (3H) -one is obtained by separation of column chromatography (petroleum ether: ethyl acetate: 4:1), wherein the yield is (85mg, 86%).1H NMR(400MHz, DMSO-d6):δ＝12.43(s,1H),8.16(dd,J1＝8.0Hz,J2＝1.6Hz,1H),7.87-7.83(m,3H),7.76(dd,J1＝8.4Hz,J2＝ 1.2Hz,1H),7.55-7.51(m,1H),7.23(s,1H),2.38(s,6H)；13C NMR(100MHz,DMSO-d6):δ＝162.63,152.92, 149.25,138.23,135.06,133.20,133.01,127.91,126.95,126.30,125.95,121.42,21.35.
EXAMPLE 11 Synthesis of 2- (3, 5-dimethoxyphenyl) -5-fluoroquinazolin-4 (3H) -one
2- ((3, 5-dimethoxybenzyl) amino) -6-fluorobenzamide (0.33mmol,100mg), elemental iodine (0.03mmol,8mg) and dimethyl sulfoxide (2ml) are sequentially added into a test tube and reacted at 130 ℃ for 6H, after the reaction is finished, the reaction liquid is extracted for 3 times by ethyl acetate, organic phases are combined and concentrated to be dry, and the 2- (3, 5-dimethoxyphenyl) -5-fluoroquinazolin-4 (3H) -one is obtained by separation of column chromatography (petroleum ether: ethyl acetate ═ 4:1), wherein the yield is (69mg, 70%).1H NMR(400MHz,DMSO-d6):δ＝12.53(s,1H),7.85-7.80(m,1H),7.59-7.56(m,1H),7.39(d,J＝2.4Hz, 2H),7.30-7.25(m,1H),6.73(t,J＝2.4Hz,1H),3.86(s,6H).13C NMR(100MHz,DMSO-d6):δ＝162.29, 161.00,159.81(d,J＝25.8Hz),153.29,151.21,135.62(d,J＝10.5Hz),134.55,124.14,113.43(d,J＝20.4Hz), 106.12,104.52,99.98,56.05；19F NMR(376MHz,DMSO-d6)δ＝111.46.
EXAMPLE 12 Synthesis of 3-methyl-2-phenylquinazolin-4 (3H) -one
2- (benzylamino) -N-methylbenzamide (0.42mmol,100mg), elemental iodine (0.04mmol,11mg) and dimethyl sulfoxide (2ml) are sequentially added into a test tube and reacted at 130 ℃ for 6H, after that, the reaction solution is extracted for 3 times by ethyl acetate, the combined organic phases are concentrated to dryness, and the 3-methyl-2-phenylquinazolin-4 (3H) -one is obtained by column chromatography (petroleum ether: ethyl acetate 4:1), with the yield of (82mg, 83%).1H NMR(400MHz,CDCl3): δ＝8.36(d,J＝8.0Hz,1H),7.77(s,2H),7.63-7.58(m,2H),7.57-7.52(m,3H),3.53(d,J＝2.0Hz,3H)；13C NMR (100MHz,CDCl3):δ＝162.73,156.14,147.33,135.42,134.33,130.09,128.91,128.02,127.51,127.01,126.69, 120.54,34.30.
EXAMPLE 13 Synthesis of 3-methyl-2- (p-tolyl) quinazolin-4 (3H) -one
Adding N-methyl-2- ((4-methylbenzyl) amino) benzamide (0.39mmol,100mg), elemental iodine (0.04mmol,11mg) and dimethyl sulfoxide (2ml) into a test tube in sequence, reacting at 130 ℃ for 6H, extracting the reaction liquid for 3 times by using ethyl acetate after the reaction is finished, combining organic phases, concentrating to be dry, and separating by using column chromatography (petroleum ether: ethyl acetate ═ 4:1) to obtain 3-methyl-2- (p-tolyl) quinazoline-4 (3H) -ketone, wherein the yield is (69mg, 70%).1H NMR (400MHz,DMSO-d6):δ＝8.19(dd,J1＝8.4Hz,J2＝1.2Hz,1H),7.86-7.81(m,1H),7.67(d,J＝8.0Hz,1H), 7.59-7.53(m,3H),7.36(d,J＝7.6Hz,2H),2.41(s,3H)；13C NMR(100MHz,DMSO-d6):δ＝162.19,156.67, 147.55,139.97,134.77,133.06,129.35,128.75,127.60,127.23,126.54,120.51,34.42,21.45.
EXAMPLE 14 Synthesis of 2- (3, 5-dimethylphenyl) -3-methyl-quinazolin-4 (3H) -one
2- ((3, 5-dimethylbenzyl) amino) -N-methylbenzamide (0.37mmol,100mg), elemental iodine (0.04mmol,11mg) and dimethyl sulfoxide (2ml) are sequentially added into a test tube and reacted at 130 ℃ for 6H, after reaction, the reaction liquid is extracted for 3 times by ethyl acetate, organic phases are combined and concentrated to be dry, and separation is carried out by column chromatography (petroleum ether: ethyl acetate ═ 4:1) to obtain 2- (3, 5-dimethylphenyl) -3-methyl quinazoline-4 (3H) -ketone, wherein the yield is (84mg, 85%).1H NMR(400MHz,DMSO-d6):δ＝8.18(dd,J1＝8.0Hz,J2＝1.2Hz,1H),7.85-7.81(m,1H),7.67(dd,J1＝8.4 Hz,J2＝1.2Hz,1H),7.57-7.52(m,1H),7.27(s,2H),7.19(s,1H),3.37(s,5H),2.39-2.33(m,6H)；13C NMR(100 MHz,DMSO-d6):δ＝162.10,156.75,147.54,138.12,135.73,134.76,131.53,127.58,127.23,126.53,126.25, 120.54,34.36,21.30.
EXAMPLE 15 Synthesis of 1, 2-Diphenyl-1H-benzo [ d ] imidazole
Will N1-benzyl-N2Sequentially adding (0.36mmol,100mg) phenyl-1, 2-diamine, elementary iodine (0.04mmol,11mg) and dimethyl sulfoxide (2ml) into a test tube, reacting at 130 ℃ for 6H, extracting the reaction liquid for 3 times by using ethyl acetate, combining organic phases, concentrating to dryness, and separating by column chromatography (petroleum ether: ethyl acetate 4:1) to obtain 1, 2-diphenyl-1H-benzo [ d]Imidazole, yield (69mg, 70%).1H NMR(400MHz,DMSO-d6): δ＝7.82(dt,J1＝7.6Hz,J2＝0.8Hz,1H),7.62-7.52(m,5H),7.47-7.35(m,5H),7.35-7.25(m,2H),7.21(dt,J＝ 8.4,1.2Hz,1H).13C NMR(100MHz,DMSO-d6):δ＝152.29,143.01,137.54,136.92,130.50,130.29,129.98, 129.58,129.31,128.81,127.99,123.81,123.20,119.85,110.92.
EXAMPLE 16 Synthesis of 9-methyl-12, 13-dihydro-6H-isoquinolin [2,1-a ] quinazolin-6-one
Adding 2- (3, 4-dihydroisoquinoline-2 (1H) -yl) -4-methylbenzamide (0.38mmol,100mg), elemental iodine (0.04mmol,11mg) and dimethyl sulfoxide (2ml) into a test tube in sequence, reacting at 130 ℃ for 6H, extracting the reaction liquid with ethyl acetate for 3 times after the reaction is finished, combining organic phases, concentrating to dryness, and separating by column chromatography (petroleum ether: ethyl acetate ═ 4:1) to obtain 9-methyl-12, 13-bis (methyl-benzamide)Hydrogen-6H-isoquinoline [2,1-a ]]Quinazolin-6-one, yield (70mg, 71%).1H NMR(400MHz,Chloroform-d):δ＝8.49(dd,J1＝8.0Hz,J2＝1.6Hz,1H),8.22(d,J＝8.0Hz,1H), 7.48(td,J1＝7.6Hz,J2＝1.2Hz,1H),7.38-7.20(m,4H),4.32(t,J＝6.8Hz,2H),3.25(t,J＝6.4Hz,2H),2.51(s, 3H).13C NMR(100MHz,CDCl3):δ＝154.85,144.82,140.77,135.83,132.60,129.48,129.11,128.58,127.67, 127.19,126.99,118.08,113.99,43.19,27.08,22.42。
Claims (6)
- A preparation method of 2-phenyl quinazolinone compounds is characterized by comprising the following steps: adding the 2- (benzylamino) benzamide compound (I), a catalyst and a solvent into a reaction reagent, reacting for 0.1-12h at 50-150 ℃, extracting with ethyl acetate after the reaction is finished, combining and concentrating organic phases, and separating by column chromatography to obtain a target product (II), wherein the reaction equation is as follows:
- 2. the process for producing a 2-phenylquinazolinone compound according to claim 1, wherein: 2- (benzylamino) benzamide (I), and the molar ratio of the catalyst is 1-2: 0.1-0.5.
- 3. The process for producing a 2-phenylquinazolinone compound according to claim 1, wherein: the catalyst is elementary iodine.
- 4. The process for producing a 2-phenylquinazolinone compound according to claim 1, wherein: the solvent comprises any one of single solvents or mixtures of dichloromethane, trichloromethane, toluene, ethyl acetate, diethyl ether, 1, 4-dioxane, 1, 2-dichloroethane, acetonitrile, ethylene glycol dimethyl ether, methyl tert-butyl ether, tetrahydrofuran, N-dimethylformamide and dimethyl sulfoxide.
- 5. The process for producing a 2-phenylquinazolinone compound according to claim 1, wherein: the reaction temperature is 130 ℃, and the reaction time is 6 h.
- 6. 2-phenylquinazolinone compounds prepared according to any one of claims 1 to 5, characterized in that: the 2-phenylquinazolinone compound comprises the following components:
any one of them.
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