CN115650924A - Green synthesis method of quinazolinone - Google Patents
Green synthesis method of quinazolinone Download PDFInfo
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- CN115650924A CN115650924A CN202211411758.5A CN202211411758A CN115650924A CN 115650924 A CN115650924 A CN 115650924A CN 202211411758 A CN202211411758 A CN 202211411758A CN 115650924 A CN115650924 A CN 115650924A
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- anthranilamide
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- AVRPFRMDMNDIDH-UHFFFAOYSA-N 1h-quinazolin-2-one Chemical compound C1=CC=CC2=NC(O)=NC=C21 AVRPFRMDMNDIDH-UHFFFAOYSA-N 0.000 title claims abstract description 28
- 238000001308 synthesis method Methods 0.000 title claims abstract description 15
- PXBFMLJZNCDSMP-UHFFFAOYSA-N 2-Aminobenzamide Chemical compound NC(=O)C1=CC=CC=C1N PXBFMLJZNCDSMP-UHFFFAOYSA-N 0.000 claims abstract description 72
- 238000006243 chemical reaction Methods 0.000 claims abstract description 63
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims abstract description 53
- YLQWCDOCJODRMT-UHFFFAOYSA-N fluoren-9-one Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3C2=C1 YLQWCDOCJODRMT-UHFFFAOYSA-N 0.000 claims abstract description 30
- 238000000034 method Methods 0.000 claims abstract description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 14
- 238000013032 photocatalytic reaction Methods 0.000 claims abstract description 13
- 239000011941 photocatalyst Substances 0.000 claims abstract description 12
- 239000003054 catalyst Substances 0.000 claims abstract description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 126
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 84
- 239000002904 solvent Substances 0.000 claims description 61
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 125000005059 halophenyl group Chemical group 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 125000004802 cyanophenyl group Chemical group 0.000 claims description 3
- 125000004464 hydroxyphenyl group Chemical group 0.000 claims description 3
- -1 methoxyphenyl Chemical group 0.000 claims description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 125000003944 tolyl group Chemical group 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 2
- 239000002994 raw material Substances 0.000 abstract description 7
- 230000015572 biosynthetic process Effects 0.000 abstract description 5
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- 229910052755 nonmetal Inorganic materials 0.000 abstract description 3
- 230000008569 process Effects 0.000 abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 138
- 239000011541 reaction mixture Substances 0.000 description 45
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 36
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 23
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
- 238000001914 filtration Methods 0.000 description 23
- 239000003208 petroleum Substances 0.000 description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- 238000001035 drying Methods 0.000 description 22
- 238000004440 column chromatography Methods 0.000 description 21
- 150000001875 compounds Chemical class 0.000 description 21
- 239000007787 solid Substances 0.000 description 21
- 238000002390 rotary evaporation Methods 0.000 description 20
- 238000002844 melting Methods 0.000 description 19
- 230000008018 melting Effects 0.000 description 19
- 235000019445 benzyl alcohol Nutrition 0.000 description 12
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 10
- 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 7
- RSKPIJGOGQGETI-UHFFFAOYSA-N 2,3-diphenylquinazolin-4-one Chemical compound C=1C=CC=CC=1C1=NC2=CC=CC=C2C(=O)N1C1=CC=CC=C1 RSKPIJGOGQGETI-UHFFFAOYSA-N 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 4
- NRCCYFAMXZIJSC-UHFFFAOYSA-N 2-(4-bromophenyl)-1h-quinazolin-4-one Chemical compound C1=CC(Br)=CC=C1C1=NC(=O)C2=CC=CC=C2N1 NRCCYFAMXZIJSC-UHFFFAOYSA-N 0.000 description 3
- 230000007613 environmental effect Effects 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 239000007800 oxidant agent Substances 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- MFGWMAAZYZSWMY-UHFFFAOYSA-N (2-naphthyl)methanol Chemical compound C1=CC=CC2=CC(CO)=CC=C21 MFGWMAAZYZSWMY-UHFFFAOYSA-N 0.000 description 2
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 2
- AKHUKZJZNGHOJU-UHFFFAOYSA-N 2-(4-chlorophenyl)-1h-quinazolin-4-one Chemical compound C1=CC(Cl)=CC=C1C1=NC(=O)C2=CC=CC=C2N1 AKHUKZJZNGHOJU-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
- MEWDLKFIQDINLZ-UHFFFAOYSA-N 2-cyclohexyl-1h-quinazolin-4-one Chemical compound N1C2=CC=CC=C2C(=O)N=C1C1CCCCC1 MEWDLKFIQDINLZ-UHFFFAOYSA-N 0.000 description 2
- MSHFRERJPWKJFX-UHFFFAOYSA-N 4-Methoxybenzyl alcohol Chemical compound COC1=CC=C(CO)C=C1 MSHFRERJPWKJFX-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- BVJSUAQZOZWCKN-UHFFFAOYSA-N p-hydroxybenzyl alcohol Chemical compound OCC1=CC=C(O)C=C1 BVJSUAQZOZWCKN-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- FSWNRRSWFBXQCL-UHFFFAOYSA-N (3-bromophenyl)methanol Chemical compound OCC1=CC=CC(Br)=C1 FSWNRRSWFBXQCL-UHFFFAOYSA-N 0.000 description 1
- PTHGDVCPCZKZKR-UHFFFAOYSA-N (4-chlorophenyl)methanol Chemical compound OCC1=CC=C(Cl)C=C1 PTHGDVCPCZKZKR-UHFFFAOYSA-N 0.000 description 1
- GEZMEIHVFSWOCA-UHFFFAOYSA-N (4-fluorophenyl)methanol Chemical compound OCC1=CC=C(F)C=C1 GEZMEIHVFSWOCA-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
- HETSSARHFAGODR-UHFFFAOYSA-N 2-(4-methoxyphenyl)-1H-quinazolin-4-one Chemical compound C1=CC(OC)=CC=C1C1=NC(=O)C2=CC=CC=C2N1 HETSSARHFAGODR-UHFFFAOYSA-N 0.000 description 1
- RUHKZVAPXHIWJH-UHFFFAOYSA-N 2-amino-4-methylbenzamide Chemical compound CC1=CC=C(C(N)=O)C(N)=C1 RUHKZVAPXHIWJH-UHFFFAOYSA-N 0.000 description 1
- REPZELLBLWMUAB-UHFFFAOYSA-N 2-amino-6-fluorobenzamide Chemical compound NC(=O)C1=C(N)C=CC=C1F REPZELLBLWMUAB-UHFFFAOYSA-N 0.000 description 1
- FDPVTENMNDHFNK-UHFFFAOYSA-N 2-amino-n-phenylbenzamide Chemical compound NC1=CC=CC=C1C(=O)NC1=CC=CC=C1 FDPVTENMNDHFNK-UHFFFAOYSA-N 0.000 description 1
- XTMWMJDTSKFKCW-UHFFFAOYSA-N 2-naphthalen-2-yl-1h-quinazolin-4-one Chemical compound C1=CC=CC2=CC(C3=NC(C4=CC=CC=C4N3)=O)=CC=C21 XTMWMJDTSKFKCW-UHFFFAOYSA-N 0.000 description 1
- SVVNZCGMBNAQFW-UHFFFAOYSA-N 2-thiophen-2-yl-1h-quinazolin-4-one Chemical compound N1C2=CC=CC=C2C(=O)N=C1C1=CC=CS1 SVVNZCGMBNAQFW-UHFFFAOYSA-N 0.000 description 1
- 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 1
- KINPFEIFSJMYNL-UHFFFAOYSA-N 4-(4-oxo-1h-quinazolin-2-yl)benzonitrile Chemical compound N1C2=CC=CC=C2C(=O)N=C1C1=CC=C(C#N)C=C1 KINPFEIFSJMYNL-UHFFFAOYSA-N 0.000 description 1
- KMTDMTZBNYGUNX-UHFFFAOYSA-N 4-methylbenzyl alcohol Chemical compound CC1=CC=C(CO)C=C1 KMTDMTZBNYGUNX-UHFFFAOYSA-N 0.000 description 1
- YBGVJFZTKPJHFV-UHFFFAOYSA-N 6-fluoro-2-phenyl-1h-quinazolin-4-one Chemical compound N1C(=O)C2=CC(F)=CC=C2N=C1C1=CC=CC=C1 YBGVJFZTKPJHFV-UHFFFAOYSA-N 0.000 description 1
- DWSBXSUAJILPPH-UHFFFAOYSA-N 7-chloro-2-phenyl-1h-quinazolin-4-one Chemical compound C=1C(Cl)=CC=C(C(N=2)=O)C=1NC=2C1=CC=CC=C1 DWSBXSUAJILPPH-UHFFFAOYSA-N 0.000 description 1
- SQHDRGBPGNFYKA-UHFFFAOYSA-N 7-methyl-2-phenyl-1h-quinazolin-4-one Chemical compound C=1C(C)=CC=C(C(N2)=O)C=1N=C2C1=CC=CC=C1 SQHDRGBPGNFYKA-UHFFFAOYSA-N 0.000 description 1
- LQRUAMXCQHSABE-UHFFFAOYSA-N C1=CC=C2C(=O)NC(CCCCCCCCC)=NC2=C1 Chemical compound C1=CC=C2C(=O)NC(CCCCCCCCC)=NC2=C1 LQRUAMXCQHSABE-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- KIMWOULVHFLJIU-UHFFFAOYSA-N N-Methylanthranilamide Chemical compound CNC(=O)C1=CC=CC=C1N KIMWOULVHFLJIU-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
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- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
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- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- VSSAZBXXNIABDN-UHFFFAOYSA-N cyclohexylmethanol Chemical compound OCC1CCCCC1 VSSAZBXXNIABDN-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 231100001261 hazardous Toxicity 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 229910052741 iridium Inorganic materials 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- VEDDBHYQWFOITD-UHFFFAOYSA-N para-bromobenzyl alcohol Chemical compound OCC1=CC=C(Br)C=C1 VEDDBHYQWFOITD-UHFFFAOYSA-N 0.000 description 1
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- ZPHGMBGIFODUMF-UHFFFAOYSA-N thiophen-2-ylmethanol Chemical compound OCC1=CC=CS1 ZPHGMBGIFODUMF-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
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Abstract
The invention discloses a green synthesis method of quinazolinone, which comprises the steps of carrying out photocatalytic reaction under the irradiation of visible light by taking anthranilamide and alcohol as raw materials, 9-fluorenone as a photocatalyst and p-toluenesulfonic acid as an auxiliary catalyst to obtain the quinazolinone. The invention uses the non-metal catalyst, thus reducing the reaction cost; the reaction condition is mild, and the reaction can be completed at room temperature; the whole synthesis process is simple to operate, simple in post-treatment, high in product yield and more environment-friendly. The method not only has higher academic value, but also has certain industrialization prospect.
Description
Technical Field
The invention relates to a synthetic method of quinazolinone, in particular to a synthetic method of quinazolinone, which is simple in operation, mild in reaction condition, green and environment-friendly, and belongs to the technical field of organic synthetic chemistry.
Background
Quinazolinone is an important nitrogen-containing heterocyclic aromatic compound, and has wide biological activity and pharmacological activity, including antibacterial, antiviral, anti-inflammatory, anticonvulsant and anticancer properties. In recent decades, various methods for synthesizing quinazolinones have been developed, but the most classical method still generates quinazolinones through oxidation of an intermediate produced by condensation of anthranilamide and aldehyde. However, these methods of synthesizing quinazolinones require the use of excess amounts of hazardous oxidizing agents (KMnO) 4 CuCl, DDQ and MnO 2 Etc.) or under the combined action of a transition metal catalyst and an oxidant to synthesize the quinazolinone. Longer reaction times and higher reaction temperatures are often required in these synthesis processes. <xnotran> ((a) I.Khan, A.Ibrar, N.Abbas and A.Saeed, eur.J.Med.Chem.76 (2014) 193-244. (b) P.P.Kung, casper, D.M.K.L.Cook, L.Wilson-Lingard, L.M.Risen, T.A.Vickers, R.Ranken, L.B.Blyn, R.Wyatt, P.D.Cook, D.Ecker, J.Med.Chem.42 (1999) 4705-4713; (c) N.J.Liverton, D.J.Armstrong, D.A.Claremon, D.C.Remy, J.J.Baldwin, R.J.Lynch, G.Zhang, R.J.Gould, bioorg.Med.Chem.Lett.8 (1998) 483-487; (d) Z.W.Wang, M.X.Wang, X.Yao, Y.Li, J.Tan, L.Z.Wang, W.T.Qiao, Y.Q.Geng, Y.X.Liu, Q.M.Wang, eur.J.Med.Chem.53 (2012) 275-282; (e) S.E.Laszlo, C.S.Quagliato, W.J.Greenlee, A.A.Patchett, R.S.L.Chang, V.J.Lotti, T.B.Chen, S.A.Scheck, K.A.Faust, S.S.Kivlighn, T.S.Schorn, G.J.Zingaro, P.K.S.Siegl, J.Med.Chem.36 (1993) 3207-3210; (f) M.M.Aly, Y.A.Mohamed, K.A.El-Bayouki, W.M.Basyouni, S.Y.Abbas, eur.J.Med.Chem.45 (2010) 3365-3373; (g) S.Kobayashi, M.Ueno, R.Suzuki and H.Ishitani, tetrahedron Lett.40 (1999) 2175-2178; (h) S.L.Cao, Y.P.Feng, Y.Y.Jiang, S.Y.Liu, G.Y.Ding, R.T.Li, bioorg.Med.Chem.Lett.15 (2005) 1915-1917; (i) D.A.Horton, G.T.Bourne, M.L.Smythe, chem.Rev.103 (2003) 893-930; (j) T.Hisano, M.Ichikawa, A.Nakagawa, M.Tsuji, chem.Pharm.Bull.23 (1975) 1910-1916; (k) R.J.Abdel-Jalil, H.M.Aldoqum, M.T.Ayoub, W.Voelter, heterocycles 65 (2005) 2061-2070; (l) Y.Mitobe, S.Ito, T.Mizutani, T.Nagase, N.Sato, S.Tokita, bioorg.Med.Chem.Lett.19 (</xnotran>2009)4075-4078；(m)K.Juvale,M.Wiese,Bioorg.Med.Chem.Lett.22(2012)6766-6769；(n)C.Balakumar,P.Lamba,D.P.Kishore,B.L.Narayana,K.V.Rao,K.Rajwinder,A.R.Rao,B.Shireesh,B.Narsaiah,Eur.J.Med.Chem.45(2010)4904-4913；(o)D.Zhan,T.Li,H.Wei,W.Weng,K.Ghandi,Q.Zeng,RSC Adv.3(2013)9325-9329.)
In addition, in the classical preparation method of quinazolinone using condensation reaction of anthranilamide and aldehyde, aldehyde not only has high toxicity, but also is easily subject to side reaction of self-condensation during the reaction, resulting in a decrease in atom economy of reaction. Therefore, the development of low-toxicity, cheap and easily-obtained green reaction raw materials for preparing quinazolinone has important research value. Compared with aldehyde, alcohol is used as a common organic reagent, and has the advantages of low toxicity, low price, easy obtainment, greenness, environmental protection and the like. In recent years, some research progress has been made in the preparation of quinazolinones by reacting anthranilamide with in situ aldehyde formation using alcohol. However, in these reported methods, it is inevitably necessary to use a metal catalyst or an equivalent of an oxidizing agent (Ir, pd, ru, mn, fe, cu, DMSO, etc.). (a) j.zhou, j.fang, j.org.chem.76 (2011) 7730-7736 (b) h.hikawa, y.ino, h.suzuki, y.yokoyama, j.org.chem.77 (2012) 7046-7051 (c) jaa.watson, c.maxwell, jmj.williams, org.biomol.chem.10 (2012) 240-243. (d) z.zhang, m.wang, c.zhang, z.zhang, j.lu, f.wang, chem.commu.51 (RSC) 9205-9207. (e) y.201n, l.li, chev.6 (65196-204) (rsc.huh) 9205-9207. (e) y.201n, l.l.li, chev.6 (65196-65204) (sarraf.s.76, sarhaq.60, sarhaki, saryao.80, saryao.75, saryama.75, saryama.r.r.r.r.t.r.r.t.r.r.r.r.r.r.t.r.r.r.r.r.f.
Therefore, from the perspective of green organic synthesis, the realization of a new method for preparing quinazolinone from alcohol and anthranilamide under mild conditions has important research value and scientific significance.
Disclosure of Invention
The invention aims to provide a green synthesis method of quinazolinone, which takes alcohol and anthranilamide as raw materials, utilizes a non-metal photocatalyst, synthesizes quinazolinone through photocatalytic reaction under the irradiation of visible light, has mild reaction conditions, simple operation and environmental protection, and provides a new thought for the synthesis of quinazolinone.
The invention is realized by the following technical scheme:
the quinazolinone provided by the invention has a structure shown in the following formula I:
in the formula I, R 1 Selected from hydrogen, methyl or halogen; r 2 Selected from phenyl, methylphenyl, methoxyphenyl, halophenyl, hydroxyphenyl, cyanophenyl, thienyl, naphthyl, octyl or cyclohexyl; r is 3 Selected from hydrogen, methyl or phenyl.
Further, in the above formula I, R 1 When it is methyl or halogen, R 1 The position on the benzene ring can be selected at will. R 2 When the phenyl group is a phenyl group substituted with a methyl group, a methoxyphenyl group, a halophenyl group, a hydroxyphenyl group, or a cyanophenyl group, the number of the substituents selected from the group consisting of a methyl group, a methoxy group, a halogen group, a hydroxyl group, and a cyano group may be one, two, or two or more, and the position of the substituent on the phenyl ring may be arbitrarily selected.
Further, in the above formula I, R 1 When the halogen is fluorine, chlorine, bromine, iodine, etc.; r 2 In the case of a halophenyl group, the halogen in the halophenyl group may be fluorine, chlorine, bromine, iodine, or the like.
The invention provides a green synthesis method of quinazolinone shown in formula I, which comprises the step of obtaining quinazolinone shown in formula I through the photocatalytic reaction of anthranilamide shown in formula II and alcohol shown in formula III; the reaction formula is as follows:
further, in the above formulae II and III, R 1 、R 2 、R 3 Is defined and describedThe definitions in the formula I are the same.
Further, the photocatalytic reaction in the invention is that alcohol is changed into aldehyde through visible light induction, and then the aldehyde and anthranilamide continue to perform cyclization oxidation reaction under the visible light induction to obtain quinazolinone. In the photocatalytic reaction, 9-fluorenone is used as a photocatalyst, p-toluenesulfonic acid is used as an auxiliary catalyst, and the photocatalytic reaction is carried out under the irradiation of blue light. The structure of 9-fluorenone is shown below:
further, the molar ratio of anthranilamide to alcohol is 1 to 1.5, preferably 1.
Further, the amount of the photocatalyst 9-fluorenone is 3-5mol%, preferably 4-5mol% of the molar amount of the anthranilamide.
Furthermore, the auxiliary catalyst p-toluenesulfonic acid is used in an amount of 10-30% of the molar amount of the anthranilamide, and preferably 10%.
Further, the blue light can be realized by a blue light lamp, and the power of the blue light lamp is 5-15w.
Further, the photocatalytic reaction is carried out in the presence of a solvent. The solvent is used for providing a medium environment for the reaction, and moreover, the solvent can influence the yield of the photocatalytic reaction. The solvent is an organic solvent, preferably at least one of acetonitrile, tetrahydrofuran and dimethyl sulfoxide (DMSO). More preferably, the solvent is a mixture of acetonitrile and DMSO.
In one embodiment of the present invention, the solvent is a mixture of acetonitrile and DMSO in a volume ratio of 8 to 10.
Furthermore, the dosage of the solvent has no special requirements, and the raw materials can be fully dispersed and dissolved, and can be adjusted according to actual conditions.
Furthermore, the method is simple to operate, and the raw materials can be reacted under the irradiation of light after being mixed. In one embodiment of the present invention, there is provided a specific process for the synthesis of quinazolinones, comprising the steps of: mixing anthranilamide, alcohol, a photocatalyst, an auxiliary catalyst and a solvent, and reacting the obtained mixture under the irradiation of a 5-15W blue light lamp to obtain quinazolinone.
Furthermore, the photocatalytic reaction condition is mild, the reaction can be carried out at room temperature, the reaction can be automatically finished when the raw materials disappear, and the reaction time is generally 10-24h.
According to the method, 9-fluorenone is used as a photocatalyst, alcohol is oxidized into aldehyde under the irradiation of blue light, and the aldehyde and anthranilamide undergo a cyclization oxidation reaction to synthesize quinazolinone. Compared with the prior art, the method has the following remarkable advantages:
1. the invention uses alcohol as raw material, and has lower toxicity compared with aldehyde.
2. The invention uses 9-fluorenone as a photocatalyst and p-toluenesulfonic acid as an auxiliary catalyst, so that the photocatalytic reaction is feasible, and the two catalysts are both non-metal components, thereby reducing the reaction cost.
3. The invention has mild reaction conditions, and can complete the reaction at room temperature.
4. The method has the advantages of simple operation, simple post-treatment, high product yield and greenness and environmental protection.
5. The invention not only has higher academic value, but also has certain industrialization prospect.
Drawings
FIG. 1 is a nuclear magnetic hydrogen spectrum of the product of example 1.
FIG. 2 is a nuclear magnetic carbon spectrum of the product of example 1.
Detailed Description
The present invention is further illustrated by the following examples, which are intended to be purely exemplary and are not to be construed as limiting the scope of the invention. Many modifications, variations and changes in the materials, methods and reaction conditions may be made without departing from the inventive concept. All such modifications, variations and changes which do not constitute inventive faculty are intended to be within the spirit and scope of the invention.
Example 1
2-Phenyl-4-quinazolinone
Anthranilamide (27.2mg, 0.2mmol), benzyl alcohol (25.9mg, 0.24mmol), 9-fluorenone (1.8mg, 5 mol%), p-toluenesulfonic acid (3.4mg, 10mol%) and 2mL of a solvent (acetonitrile: DMSO volume ratio, 9: 1) were added to a 15mL reaction tube. The reaction mixture was reacted for 16 hours under the irradiation of a 10w blue light lamp, and after the completion of the reaction, 100mL of water was added to the reaction mixture, extracted with ethyl acetate (3X 50 mL), and anhydrous MgSO (MgSO) was extracted 4 Drying, filtration, rotary evaporation to remove the solvent, and then column chromatography (developer: petroleum ether/ethyl acetate volume ratio =10: 1) gave the pure title compound as a white solid (40.4 mg), yield: 91.3 percent and the melting point is 237-238 ℃.
Example 2- (4-methylphenyl) -4- [3H ] quinazolinone
2-(p-Tolyl)quinazolin-4(3H)-one
Anthranilamide (27.2mg, 0.2mmol), 4-methylbenzyl alcohol (29.3mg, 0.24mmol), 9-fluorenone (1.8mg, 5 mol%), p-methylbenzenesulfonic acid (3.4mg, 10mol%) and 2mL of a solvent (acetonitrile: DMSO volume ratio 9) were added to a 15mL reaction tube. The reaction mixture was reacted for 16 hours under irradiation of a 10w blue light lamp, and after completion of the reaction, 100mL of water was added to the reaction mixture, extracted with ethyl acetate (3X 50 mL), and anhydrous MgSO 4 Drying, filtration, rotary evaporation to remove the solvent, and column chromatography (developer: petroleum ether/ethyl acetate volume ratio =10: 1) gave the pure title compound as a white solid (42.2 mg), yield: 89.3 percent and the melting point of 244-245 ℃.
1 H NMR(400MHz,[D 6 ]DMSO)δ12.49(br s,1H),8.15(d,J＝7.6Hz,1H),8.10(d,J＝7.6Hz,2H),7.83(t,J＝7.4Hz,1H),7.73(d,J＝8.0Hz,1H),7.50(t,J＝7.2Hz,1H),7.36(d,J＝7.6Hz,2H),2.39(s,3H)； 13 C NMR(100MHz,[D 6 ]DMSO)δ162.3,152.2,148.9,141.5,134.6,129.9,129.2,127.7,127.5,126.4,125.9,120.9,21.0.
Example 3
2-(4-Methoxyphenyl)quinazolin-4(3H)-one
Anthranilamide (27.2mg, 0.2mmol), 4-methoxybenzyl alcohol (33.1mg, 0.24mmol), 9-fluorenone (1.8mg, 5 mol%), p-toluenesulfonic acid (3.4mg, 10mol%) and 2mL of a solvent (acetonitrile: DMSO volume ratio 9) were added to a 15mL reaction tube. The reaction mixture was reacted for 16 hours under irradiation of a 10w blue light lamp, and after completion of the reaction, 100mL of water was added to the reaction mixture, extracted with ethyl acetate (3X 50 mL), and anhydrous MgSO 4 Drying, filtration, rotary evaporation to remove the solvent, and then column chromatography (developer: petroleum ether/ethyl acetate volume ratio =10: 1) gave the pure title compound as a white solid (44.6 mg), yield: 88.5 percent and the melting point is 245-247 ℃.
1 H NMR(400MHz,[D 6 ]DMSO)δ12.43(br s,1H),8.20(d,J＝7.8Hz,2H),8.14(d,J＝7.4Hz,1H),7.82(t,J＝6.9Hz,1H),7.71(d,J＝7.7Hz,1H),7.49(t,J＝6.8Hz,2H),7.10(d,J＝7.8Hz,2H),7.85(s,3H)； 13 C NMR(100MHz,[D 6 ]DMSO)δ162.4,161.9,151.9,149.0,134.6,129.5,127.3,126.2,125.9,124.8,120.7,114.1,55.5.
Example 4
2-(4-Fluorophenyl)quinazolin-4(3H)-one
Anthranilamide (27.2mg, 0.2mmol), 4-fluorobenzyl alcohol(30.2mg, 0.24mmol), 9-fluorenone (1.8mg, 5 mol%), p-toluenesulfonic acid (3.4mg, 10mol%) and 2mL of a solvent (acetonitrile: DMSO volume ratio 9) were charged into a 15mL reaction tube. The reaction mixture was reacted for 16 hours under irradiation of a 10w blue light lamp, and after completion of the reaction, 100mL of water was added to the reaction mixture, extracted with ethyl acetate (3X 50 mL), and anhydrous MgSO 4 Drying, filtration, rotary evaporation to remove the solvent, and then column chromatography (developer: petroleum ether/ethyl acetate volume ratio =10: 1) gave the pure title compound as a white solid (40.8 mg), yield: 85.1 percent and a melting point of 258-259 ℃.
1 H NMR(400MHz,[D 6 ]DMSO)δ12.59(br s,1H),8.25(t,J＝6.2Hz,2H),8.15(d,J＝7.8Hz,1H),7.84(t,J＝7.56Hz,1H),7.74(d,J＝8.0Hz,1H),7.52(t,J＝7.4Hz,1H),7.39(t,J＝8.2Hz,2H)； 13 C NMR(100MHz,[D 6 ]DMSO)δ165.3(d,J C-F ＝250.0Hz),162.3,151.4,148.7,134.7,130.5(d,J＝9.0Hz),129.3(d,J＝2.4Hz),127.5,126.6,125.9,120.9,115.8(d,J＝21.8Hz).
Example 5 2- (4-chlorophenyl) -4- [3H ] quinazolinone
2-(4-Chlorophenyl)quinazolin-4(3H)-one
Anthranilamide (27.2mg, 0.2mmol), 4-chlorobenzyl alcohol (34.1mg, 0.24mmol), 9-fluorenone (1.8mg, 5 mol%), p-toluenesulfonic acid (3.4mg, 10mol%) and 2mL of a solvent (acetonitrile: DMSO volume ratio, 9: 1) were added to a 15mL reaction tube. The reaction mixture was reacted for 16 hours under the irradiation of a 10w blue light lamp, and after the completion of the reaction, 100mL of water was added to the reaction mixture, extracted with ethyl acetate (3X 50 mL), and anhydrous MgSO (MgSO) was extracted 4 Drying, filtration, rotary evaporation to remove the solvent, and then column chromatography (developer: petroleum ether/ethyl acetate volume ratio =10: 1) gave the pure title compound as a white solid (40.8 mg), yield: 85.1 percent and the melting point is 300-301 ℃.
1 H NMR(400MHz,[D 6 ]DMSO)δ12.62(br s,1H),8.21-8.14(m,3H),7.84(t,J＝7.3Hz,1H),7.75(d,J＝8.0Hz,1H),7.63(d,J＝7.9Hz,1H),7.53(t,J＝7.0Hz,1H)； 13 C NMR(100MHz,[D 6 ]DMSO)δ162.2,151.4,148.6,136.3,134.7,131.6,129.7,128.7,127.6,126.8,125.9,121.0.
Example 6 [ 2- (4-bromophenyl) -4- [3H ] quinazolinone ]
2-(4-Bromophenyl)quinazolin-4(3H)-one
Anthranilamide (27.2mg, 0.2mmol), 4-bromobenzyl alcohol (44.6mg, 0.24mmol), 9-fluorenone (1.8mg, 5 mol%), p-toluenesulfonic acid (3.4mg, 10mol%) and 2mL of a solvent (acetonitrile: DMSO volume ratio 9) were added to a 15mL reaction tube. The reaction mixture was reacted for 16 hours under the irradiation of a 10w blue light lamp, and after the completion of the reaction, 100mL of water was added to the reaction mixture, extracted with ethyl acetate (3X 50 mL), and anhydrous MgSO (MgSO) was extracted 4 Drying, filtration, rotary evaporation to remove the solvent, and column chromatography (developer: petroleum ether/ethyl acetate volume ratio =10: 1) gave the pure title compound as a white solid (49.6 mg), yield: 82.3 percent and the melting point is 296-297 ℃.
1 H NMR(400MHz,[D 6 ]DMSO)δ12.62(br s,1H),8.16-8.11(m,3H),7.84(t,J＝7.4Hz,1H),7.77-7.73(m,3H)； 13 C NMR(100MHz,[D 6 ]DMSO)δ162.2,151.5,148.6,134.8,132.0,131.7,129.9,127.6,126.9,125.9,125.3,121.1.
Example 7
2-(4-Bromophenyl)quinazolin-4(3H)-one
Anthranilamide (27.2mg, 0.2mmol), 4-hydroxybenzyl alcohol (29.8mg, 0.24mmol), 9-fluorenone (1.8mg, 5 mol%), p-toluenesulfonic acid (3.4mg, 10mol%) and 2mL of a solvent (acetonitrile: DMSO volume ratio 9) were added to a 15mL reaction tube. The reaction mixture was irradiated with a 10w blue light lampAfter the reaction was completed for 16 hours, 100mL of water was added to the reaction mixture, followed by extraction with ethyl acetate (3X 50 mL) and anhydrous MgSO 4 Drying, filtration, rotary evaporation to remove the solvent, and then column chromatography (developer: petroleum ether/ethyl acetate volume ratio =10: 1) gave the pure title compound as a white solid (42.4 mg), yield: 89.0% melting Point>300℃。
1 H NMR(400MHz,[D 6 ]DMSO)δ12.32(s,1H),10.19(s,1H),8.10(m,3H),7.79(t,J＝7.0Hz,1H),7.68(d,J＝7.8Hz,1H),7.45(t,J＝6.9Hz,1H),6.90(d,J＝7.6Hz,2H)； 13 C NMR(100MHz,[D 6 ]DMSO)δ162.5,160.6,152.2,149.1,134.6,129.7,127.2,126.0,125.9,123.3,120.6,115.4.
Example 8
4-(4-Oxo-3,4-dihydroquinazolin-2-yl)benzonitrile
Anthranilamide (27.2mg, 0.2mmol), 3-bromobenzyl alcohol (31.9mg, 0.24mmol), 9-fluorenone (1.8mg, 5 mol%), p-toluenesulfonic acid (3.4mg, 10mol%) and 2mL of a solvent (acetonitrile: DMSO volume ratio 9) were added to a 15mL reaction tube. The reaction mixture was reacted for 16 hours under the irradiation of a 10w blue light lamp, and after the completion of the reaction, 100mL of water was added to the reaction mixture, extracted with ethyl acetate (3X 50 mL), and anhydrous MgSO (MgSO) was extracted 4 Drying, filtration, rotary evaporation to remove the solvent, and then column chromatography (developer: petroleum ether/ethyl acetate volume ratio =10: 1) gave the pure title compound as a white solid (43.6 mg), yield: 88.2 percent and the melting point is 281-282 ℃.
1 H NMR(400MHz,[D 6 ]DMSO)δ12.76(br s,1H),8.34(d,J＝7.8Hz,2H),8.18(d,J＝7.6Hz,1H),8.05(d,J＝7.8Hz,2H),7.89(t,J＝7.4Hz,1H),7.79(d,J＝7.7Hz,1H),7.59(t,J＝7.1Hz,1H)； 13 C NMR(100MHz,[D 6 ]DMSO)δ162.2,151.0,148.3,136.9,134.8,132.6,128.7,127.8,127.3,126.0,121.2,118.4,113.6.
Example 9
2-(Thiophen-2-yl)quinazolin-4(3H)-one
Anthranilamide (27.2mg, 0.2mmol), thiophene-2-methanol (27.4mg, 0.24mmol), 9-fluorenone (1.8mg, 5 mol%), p-toluenesulfonic acid (3.4mg, 10mol%) and 2mL of a solvent (acetonitrile: DMSO volume ratio 9) were added to a 15mL reaction tube. The reaction mixture was reacted for 16 hours under irradiation of a 10w blue light lamp, and after completion of the reaction, 100mL of water was added to the reaction mixture, extracted with ethyl acetate (3X 50 mL), and anhydrous MgSO 4 Drying, filtration, rotary evaporation to remove the solvent, and then column chromatography (developer: petroleum ether/ethyl acetate volume ratio =10: 1) gave the pure title compound as a white solid (36.5 mg), yield: 80.0 percent and the melting point is 272-273 ℃.
1 H NMR(400MHz,[D 6 ]DMSO)δ12.67(br s,1H),8.24-8.22(m,1H),8.13(d,J＝7.8Hz,1H),7.88(d,J＝7.8Hz,1H),7.80(t,J＝7.5Hz,1H),7.66(d,J＝8.1Hz,1H),7.49(t,J＝7.3Hz,1H),7.25-7.22(m,1H)； 13 C NMR(100MHz,[D 6 ]DMSO)δ161.8,148.7,147.9,137.4,134.7,132.3,129.4,128.6,127.0,126.4,126.0,120.9.
Example 10
2-(Naphthalen-2-yl)quinazolin-4(3H)-one
Anthranilamide (27.2mg, 0.2mmol), 2-naphthylmethanol (38.0mg, 0.24mmol), 9-fluorenone (1.8mg, 5 mol%), p-toluenesulfonic acid (3.4mg, 10mol%) and 2mL of a solvent (acetonitrile: DMSO volume ratio 9) were added to a 15mL reaction tube. The reaction mixture was reacted for 16 hours under irradiation of a 10w blue light lamp, and after completion of the reaction, 100mL of water was added to the reaction mixture, extracted with ethyl acetate (3X 50 mL), and anhydrous MgSO 4 Drying, filtering, rotary evaporating to remove solvent, and introducingColumn chromatography (developer: petroleum ether/ethyl acetate volume ratio = 10) gave the pure title compound as a white solid (47.5 mg), yield: 87.2 percent and the melting point is 212-214 ℃.
1 H NMR(400MHz,[D 6 ]DMSO)δ12.69(s,1H),8.82(s,1H),8.31(d,J＝8.4Hz,1H),8.19(d,J＝7.5Hz,1H),8.08-8.05(m,2H),8.02(d,J＝7.0Hz,1H),7.87(t,J＝7.5Hz,1H),7,81(d,J＝7.8Hz,1H),7.67-7.61(m,2H),7.85(t,J＝7.3Hz,1H)； 13 C NMR(100MHz,[D 6 ]DMSO)δ162.3,152.3,148.8,134.7,134.2,132.3,130.0,129.0,128.2,128.2,128.0,127.7,127.6,127.0,126.7,126.0,124.5,121.1.
Example 11 2-cyclohexyl-4- [3H ] quinazolinone
2-Cyclohexylquinazolin-4(3H)-one
Anthranilamide (27mg, 0.2mmol), cyclohexylmethanol (27.4 mg, 0.24mmol), 9-fluorenone (1.8mg, 5 mol%), p-toluenesulfonic acid (3.4 mg,10 mol%) and 2mL of a solvent (acetonitrile: DMSO volume ratio 9. The reaction mixture was reacted for 16 hours under irradiation of a 10w blue light lamp, and after completion of the reaction, 100mL of water was added to the reaction mixture, extracted with ethyl acetate (3X 50 mL), and anhydrous MgSO 4 Drying, filtration, rotary evaporation to remove the solvent, and then column chromatography (developer: petroleum ether/ethyl acetate volume ratio =10: 1) gave the pure title compound as a white solid (20.8 mg), yield: 45.6 percent and the melting point is 229-231 ℃.
1 H NMR(400MHz,[D 6 ]DMSO)δ12.09(br s,1H),8.08(d,J＝7.8Hz,1H),7.76(t,J＝7.5Hz,1H),7.60(d,J＝8.0Hz,1H),7.44(t,J＝7.4Hz,1H),2.57(t,J＝11.3Hz,1H),1.91-1.78(m,4H),1.68-1.53(m,3H),1.31-1.20(m,3H)； 13 C NMR(100MHz,[D 6 ]DMSO)δ162.0,160.8,149.0,134.3,127.0,126.0,125.7,121.9,42.8,30.2,25.6,25.4.
Example 12
2-Nonylquinazolin-4(3H)-one
Anthranilamide (27.2mg, 0.2mmol), octanol (31.3mg, 0.24mmol), 9-fluorenone (1.8mg, 5 mol%), p-toluenesulfonic acid (3.4mg, 10mol%) and 2mL of a solvent (acetonitrile: DMSO volume ratio 9). The reaction mixture was reacted for 16 hours under irradiation of a 10w blue light lamp, and after completion of the reaction, 100mL of water was added to the reaction mixture, extracted with ethyl acetate (3X 50 mL), and anhydrous MgSO 4 Drying, filtration, rotary evaporation to remove the solvent, and then column chromatography (developer: petroleum ether/ethyl acetate volume ratio =10: 1) gave the pure title compound as a white solid (12.0 mg), yield: 32.0 percent and the melting point is 140-142 ℃.
1 H NMR(400MHz,[D 6 ]DMSO)δ12.18(br s,1H),8.08(d,J＝7.9Hz,1H),7.77(t,J＝7.5Hz,1H),7.60(d,J＝8.1Hz,1H),7.45(t,J＝7.4Hz,1H),2.59(t,J＝7.5Hz,2H),1.73-1.70(m,2H),1.29-1.23(m,12H),0.86-0.83(m,3H)； 13 C NMR(100MHz,[D 6 ]DMSO)δ161.9,157.7,148.7,134.4,126.6,126.0,125.7,120.7,34.5,31.1,28.5,28.4,26.8,22.1,14.0
Example 13-methyl-2-phenyl-4- [3H ] quinazolinone
7-Methyl-2-phenylquinazolin-4(3H)-one
2-amino-4-methylbenzamide (30.0mg, 0.2mmol), benzyl alcohol (25.9mg, 0.24mmol), 9-fluorenone (1.8mg, 5 mol%), p-methylbenzenesulfonic acid (3.4mg, 10mol%), and 2mL of a solvent (acetonitrile: DMSO volume ratio, 9) were added to a 15mL reaction tube. The reaction mixture was reacted for 16 hours under the irradiation of a 10w blue light lamp, and after the completion of the reaction, 100mL of water was added to the reaction mixture, extracted with ethyl acetate (3X 50 mL), and anhydrous MgSO (MgSO) was extracted 4 Drying, filtering, rotary evaporating to remove solvent, and performing column chromatography (developer: petroleum ether/ethyl acetate volume ratio)=10, 1) pure target compound was obtained as a white solid (39.8 mg), yield: 84.2 percent and the melting point of 238-238 ℃.
1 H NMR(400MHz,[D 6 ]DMSO)δ12.45(br s,1H),8.18(d,J＝6.9Hz,2H),8.13(d,J＝7.8Hz,1H),8.04(d,J＝7.9Hz,1H),7.60-7.53(m,4H),7.34(d,J＝7.9Hz,1H),2.46(s,3H)； 13 C NMR(100MHz,[D 6 ]DMSO)δ162.2,152.4,148.9,145.1,132.8,131.4,128.7,128.1,127.8,127.2,125.8,118.6,21.4.
Example 14-fluoro-2-phenyl-4- [3H ] quinazolinone
6-Fluoro-2-phenylquinazolin-4(3H)-one
2-amino-6-fluorobenzamide (30.8mg, 0.2mmol), benzyl alcohol (25.9mg, 0.24mmol), 9-fluorenone (1.8mg, 5 mol%), p-methylbenzenesulfonic acid (3.4mg, 10mol%), and 2mL of a solvent (acetonitrile: DMSO volume ratio, 9) were added to a 15mL reaction tube. The reaction mixture was reacted for 16 hours under irradiation of a 10w blue light lamp, and after completion of the reaction, 100mL of water was added to the reaction mixture, extracted with ethyl acetate (3X 50 mL), and anhydrous MgSO 4 Drying, filtration, rotary evaporation to remove the solvent, and then column chromatography (developer: petroleum ether/ethyl acetate volume ratio =10: 1) gave the pure title compound as a white solid (39.4 mg), yield: 82.1% and a melting point of 278-279 ℃.
1 H NMR(400MHz,[D 6 ]DMSO)δ12.66(br s,1H),8.17(d,J＝6.8Hz,2H),7.83(d,J＝8.2Hz,2H),7.72(t,J＝8.3Hz,1H),7.60-7.53(m,3H)； 13 C NMR(100MHz,[D 6 ]DMSO)δ161.8,161.2(d,J C-F ＝243.7Hz),152.0,145.6,132.6,131.5,130.4(d,J C-F ＝8.0Hz),128.7,127.8,123.3(d,J C-F ＝23.9Hz),122.3(d,J C-F ＝8.3Hz),110.7(d,J C-F ＝23.1Hz).
Example 15-chloro-2-phenyl-4- [3H ] quinazolinone
7-Chloro-2-phenylquinazolin-4(3H)-one
2-amino-7-chlorobenzamide (34.1mg, 0.2mmol), benzyl alcohol (25.9mg, 0.24mmol), 9-fluorenone (1.8mg, 5 mol%), p-methylbenzenesulfonic acid (3.4mg, 10mol%), and 2mL of a solvent (acetonitrile: DMSO volume ratio, 9) were added to a 15mL reaction tube. The reaction mixture was reacted for 16 hours under irradiation of a 10w blue light lamp, and after completion of the reaction, 100mL of water was added to the reaction mixture, extracted with ethyl acetate (3X 50 mL), and anhydrous MgSO 4 Drying, filtration, rotary evaporation to remove the solvent, and then column chromatography (developer: petroleum ether/ethyl acetate volume ratio =10: 1) gave the pure title compound as a white solid (43.6 mg), yield: 85.1 percent and the melting point is 279 to 287 ℃.
1 H NMR(400MHz,[D 6 ]DMSO)δ12.69(br s,1H),8.18-8.13(m,3H),7.79(s,1H),7.61-7.54(m,4H)； 13 C NMR(100MHz,[D 6 ]DMSO)δ161.7,153.8,149.9,139.2,132.4,131.8,128.7,128.0,128.9,126.9,126.6,119.8.
Example 16-phenyl-2-phenyl-4- [3H ] quinazolinone
3-Methyl-2-phenylquinazolin-4(3H)-one
2-amino-N-methylbenzamide (30.0 mg, 0.2mmol), benzyl alcohol (25.9mg, 0.24mmol), 9-fluorenone (1.8mg, 5mol%), p-methylbenzenesulfonic acid (3.4mg, 10mol%), and 2mL of a solvent (acetonitrile: DMSO volume ratio, 9) were added to a 15mL reaction tube. The reaction mixture was reacted for 16 hours under irradiation of a 10w blue light lamp, and after completion of the reaction, 100mL of water was added to the reaction mixture, extracted with ethyl acetate (3X 50 mL), and anhydrous MgSO 4 Drying, filtration, rotary evaporation to remove the solvent, and then column chromatography (developer: petroleum ether/ethyl acetate volume ratio =10: 1) gave the pure title compound as a white solid (40.2 mg), yield: 85.0 percent and the melting point of 112-114 ℃.
1 H NMR(400MHz,[D 6 ]DMSO)δ8.19(d,J＝7.9Hz,1H),7.83(t,J＝7.3Hz,1H),7.68(d,J＝6.6Hz,3H),7.58-7.53(m,4H),3.36(s,3H)； 13 C NMR(100MHz,[D 6 ]DMSO)δ161.7,156.2,147.1,135.4,134.4,129.9,128.5,128.3,127.2,126.9,126.1,120.2,34.0.
Example 17-Diphenyl-4- [3H ] quinazolinone
2,3-diphenylquinazolin-4(3H)-one
2-amino-N-phenylbenzamide (42.4mg, 0.2mmol), benzyl alcohol (25.9mg, 0.24mmol), 9-fluorenone (1.8mg, 5mol%), p-methylbenzenesulfonic acid (3.4mg, 10mol%), and 2mL of a solvent (acetonitrile: DMSO volume ratio, 9) were added to a 15mL reaction tube. The reaction mixture was reacted for 16 hours under irradiation of a 10w blue light lamp, and after completion of the reaction, 100mL of water was added to the reaction mixture, extracted with ethyl acetate (3X 50 mL), and anhydrous MgSO 4 Drying, filtration, rotary evaporation to remove the solvent, and then column chromatography (developer: petroleum ether/ethyl acetate volume ratio =10: 1) gave the pure title compound as a white solid (47.1 mg), yield: 78.8 percent and a melting point of 112-114 ℃.
1 H NMR(400MHz,[D 6 ]DMSO)δ8.21(d,J＝7.8Hz,1H),7.90(t,J＝7.5Hz,1H),7.79(d,J＝8.1Hz,1H),7.61(t,J＝7.4Hz,1H),7.39-7.21(m,10H)； 13 C NMR(100MHz,[D 6 ]DMSO)δ161.4,155.2,147.3,137.8,135.6,134.8,129.5,128.9,128.9,128.6,128.2,127.5,127.4,127.2,126.5,120.8.
Example 18 diphenyl-4- [3H ] quinazolinone
Anthranilamide (27.2mg, 0.2mmol), benzyl alcohol (25.9mg, 0.24mmol), 9-fluorenone, p-methylbenzenesulfonic acid (3.4mg, 10mol%), and 2mL of a solvent (acetonitrile: DMSO volume ratio, 9). The reaction mixture was reacted for 16 hours under the irradiation of a 10w blue light lamp, and after the completion of the reaction, 100mL of water was added to the reaction mixture, extracted with ethyl acetate (3X 50 mL), and anhydrous MgSO (MgSO) was extracted 4 Drying, filtering, rotary evaporating to remove solvent, and introducingColumn chromatography (developing solvent: petroleum ether/ethyl acetate =10: 1) gave the pure target compound as a white solid, 2-phenyl-4-quinazolinone.
The product obtained by varying the amount of 9-fluorenone was as follows:
example 19 2, 3-Diphenyl-4- [3H ] quinazolinone
Anthranilamide (27.2mg, 0.2mmol), benzyl alcohol (25.9mg, 0.24mmol), 9-fluorenone (1.8mg, 5 mol%), p-toluenesulfonic acid and 2mL of solvent (acetonitrile: DMSO volume ratio 9: 1) were added to a 15mL reaction tube. The reaction mixture was reacted for 16 hours under irradiation of a 10w blue light lamp, and after completion of the reaction, 100mL of water was added to the reaction mixture, extracted with ethyl acetate (3X 50 mL), and anhydrous MgSO 4 Drying, filtration, rotary evaporation to remove the solvent, and column chromatography (developer: petroleum ether/ethyl acetate = 10) gave the pure target compound as a white solid, 2-phenyl-4-quinazolinone.
The amount of p-toluenesulfonic acid was varied and the product obtained was as follows:
example 20 diphenyl-4- [3H ] quinazolinone
Anthranilamide (27.2mg, 0.2mmol), benzyl alcohol (25.9mg, 0.24mmol), 9-fluorenone (1.8mg, 5 mol%), p-toluenesulfonic acid (3.4mg, 10mol%) and 2mL of a solvent (acetonitrile: DMSO volume ratio, 9: 1) were added to a 15mL reaction tube. The reaction mixture was reacted for 16 hours under the irradiation of a blue light lamp, and after the reaction was completed, 100mL of water was added to the reaction solution, extracted with ethyl acetate (3X 50 mL), and anhydrous MgSO 4 Drying, filtration, rotary evaporation to remove the solvent, and column chromatography (developing solvent: petroleum ether/ethyl acetate = 10) to obtain pure target compound as white solid 2-
Phenyl-4-quinazolinone.
The power of the blue light lamp was varied and the product obtained was as follows:
| numbering | Power of blue light lamp | Quality of the product | Product yield | Melting point of |
| 1 | 5w | 36.5mg | 82.5％ | 237-238 |
| 2 | 15w | 40.6mg | 91.8％ | 237-238℃ |
Example 21-diphenyl-4- [3H ] quinazolinone
Anthranilamide (27.2mg, 0.2mmol), benzyl alcohol (25.9mg, 0.24mmol), 9-fluorenone (1.8mg, 5 mol%), p-toluenesulfonic acid (3.4mg, 10mol%) and 2mL of a solvent (acetonitrile: DMSO volume ratio, 9: 1) were added to a 15mL reaction tube. The reaction mixture was reacted under irradiation of a 10w blue light lamp, and after completion of the reaction, 100mL of water was added to the reaction mixture, extracted with ethyl acetate (3X 50 mL), and anhydrous MgSO 4 The mixture is dried and then is dried,filtration and rotary evaporation to remove the solvent followed by column chromatography (developer: petroleum ether/ethyl acetate =10: 1) gave the pure target compound as a white solid, 2-phenyl-4-quinazolinone.
The reaction time was varied and the product obtained was as follows:
| numbering | Reaction time | Quality of the product | Product yield | Melting point of the |
| 1 | 10h | 36.4mg | 82.3％ | 237-238 |
| 2 | 24h | 40.7mg | 92.0％ | 237-238℃ |
Example 22-diphenyl-4- [3H ] quinazolinone
Anthranilamide (27.2mg, 0.2mmol), benzyl alcohol (25.9mg, 0.24mmol), 9-fluorenone (1.8mg, 5mol%), p-toluenesulfonic acid (3.4mg, 10mol%) and solvent (2 mL) were added to 15mL of transAnd is applied to the pipe. The reaction mixture was reacted for 16 hours under irradiation of a 10w blue light lamp, and after completion of the reaction, 100mL of water was added to the reaction mixture, extracted with ethyl acetate (3X 50 mL), and anhydrous MgSO 4 Drying, filtration, rotary evaporation to remove the solvent, followed by column chromatography (developer: petroleum ether/ethyl acetate =10: 1) gave the product 2-phenyl-4-quinazolinone.
The solvent was varied, and the obtained product was as follows:
example 23-diphenyl-4- [3H ] quinazolinone
Anthranilamide (27.2mg, 0.2mmol), benzyl alcohol (25.9mg, 0.24mmol), photocatalyst, p-toluenesulfonic acid (3.4mg, 10mol%) and 2mL of solvent (acetonitrile: DMSO volume ratio, 9) were added to a 15mL reaction tube. The reaction mixture was reacted for 16 hours under the irradiation of a 10w blue light lamp, and after the completion of the reaction, 100mL of water was added to the reaction mixture, extracted with ethyl acetate (3X 50 mL), and anhydrous MgSO (MgSO) was extracted 4 Drying, filtration, rotary evaporation to remove the solvent, and then column chromatography (developer: petroleum ether/ethyl acetate = 10) to afford the product 2-phenyl-4-quinazolinone.
The photocatalyst was changed in kind, and the obtained product was as follows:
Claims (10)
1. a green synthesis method of quinazolinone is characterized in that: the method comprises the steps of carrying out a photocatalytic reaction on anthranilamide shown in a formula II and alcohol shown in a formula III to obtain quinazolinone shown in a formula I; the reaction formula is as follows:
2. a green color synthesis method according to claim 1, characterized in that: in the formulae I, II and III, R 1 Selected from hydrogen, methyl or halogen; r is 2 Selected from phenyl, methylphenyl, methoxyphenyl, halophenyl, hydroxyphenyl, cyanophenyl, thienyl, naphthyl, octyl or cyclohexyl; r is 3 Selected from hydrogen, methyl or phenyl.
3. A green color synthesis method according to claim 1, characterized in that: the photocatalytic reaction takes 9-fluorenone as a photocatalyst and takes p-toluenesulfonic acid as an auxiliary catalyst.
4. A green color synthesis method according to claim 3, characterized in that: the using amount of the photocatalyst is 3-5% of the molar weight of the anthranilamide; the dosage of the p-toluenesulfonic acid is 10 to 30 percent of the molar weight of the anthranilamide.
5. A green synthesis method according to claim 1 or 3, characterized in that: the photocatalytic reaction is carried out under the irradiation of blue light.
6. The green color synthesis method according to claim 5, wherein: the power of the blue light is 5-15w.
7. The green color synthesis method according to claim 1, wherein: the molar ratio of anthranilamide to alcohol is 1.
8. A green synthesis method according to claim 1, 2,3, 4 or 7, characterized in that: the reaction is carried out in the presence of a solvent, the solvent being at least one of acetonitrile, tetrahydrofuran and dimethyl sulfoxide (DMSO); preferably, the solvent is a mixture of acetonitrile and dimethyl sulfoxide, and more preferably, the volume ratio of acetonitrile to dimethyl sulfoxide is 8-10.
9. A green synthesis method according to any one of claims 1 to 8, characterized by comprising the following specific steps: mixing anthranilamide, alcohol, a photocatalyst, an auxiliary catalyst and a solvent, and reacting the obtained mixture under the irradiation of a 5-15W blue light lamp to obtain quinazolinone.
10. A green synthesis method according to claim 1, 2,3, 4 or 7, characterized in that: the reaction temperature was room temperature.
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| CN111777564A (en) * | 2020-08-11 | 2020-10-16 | 许昌学院 | Method for synthesizing quinazolinone compound through photocatalytic alcohol oxidation in aqueous phase |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN108822046A (en) * | 2018-08-28 | 2018-11-16 | 河南大学 | The method of one pot process quianzolinones |
| CN111777564A (en) * | 2020-08-11 | 2020-10-16 | 许昌学院 | Method for synthesizing quinazolinone compound through photocatalytic alcohol oxidation in aqueous phase |
Non-Patent Citations (1)
| Title |
|---|
| QIANGQIANG XIA: ""Visible-Light-Enabled Selective Oxidation of Primary Alcohols through Hydrogen-Atom Transfer and its Application in the Synthesis of Quinazolinones"", 《ASIAN J. ORG. CHEM》, 31 December 2019 (2019-12-31), pages 1933 * |
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