CN112062681A - Preparation method of trifluoromethylated aniline compound - Google Patents
Preparation method of trifluoromethylated aniline compound Download PDFInfo
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- CN112062681A CN112062681A CN202010724979.2A CN202010724979A CN112062681A CN 112062681 A CN112062681 A CN 112062681A CN 202010724979 A CN202010724979 A CN 202010724979A CN 112062681 A CN112062681 A CN 112062681A
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- formula
- extraction
- ethyl acetate
- reaction
- aniline compound
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- -1 trifluoromethylated aniline compound Chemical class 0.000 title claims abstract description 43
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims abstract description 200
- 238000006243 chemical reaction Methods 0.000 claims abstract description 137
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 76
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 74
- 239000012046 mixed solvent Substances 0.000 claims abstract description 40
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims abstract description 27
- 239000011941 photocatalyst Substances 0.000 claims abstract description 20
- 150000001448 anilines Chemical class 0.000 claims abstract description 12
- 239000011541 reaction mixture Substances 0.000 claims abstract description 9
- 239000012429 reaction media Substances 0.000 claims abstract description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 420
- 238000000605 extraction Methods 0.000 claims description 204
- 150000001875 compounds Chemical class 0.000 claims description 148
- 239000012044 organic layer Substances 0.000 claims description 76
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 72
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 68
- 239000007864 aqueous solution Substances 0.000 claims description 68
- 238000001035 drying Methods 0.000 claims description 68
- 239000003480 eluent Substances 0.000 claims description 63
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 claims description 56
- 239000002904 solvent Substances 0.000 claims description 40
- 238000001704 evaporation Methods 0.000 claims description 39
- 239000000706 filtrate Substances 0.000 claims description 37
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 36
- 238000001914 filtration Methods 0.000 claims description 36
- 239000010410 layer Substances 0.000 claims description 36
- 239000003208 petroleum Substances 0.000 claims description 36
- 238000010898 silica gel chromatography Methods 0.000 claims description 36
- 239000000047 product Substances 0.000 claims description 17
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 239000012043 crude product Substances 0.000 claims description 9
- 239000011259 mixed solution Substances 0.000 claims description 6
- 238000004440 column chromatography Methods 0.000 claims description 4
- SEACYXSIPDVVMV-UHFFFAOYSA-L eosin Y Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C([O-])=C(Br)C=C21 SEACYXSIPDVVMV-UHFFFAOYSA-L 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- UEEXRMUCXBPYOV-UHFFFAOYSA-N iridium;2-phenylpyridine Chemical compound [Ir].C1=CC=CC=C1C1=CC=CC=N1.C1=CC=CC=C1C1=CC=CC=N1.C1=CC=CC=C1C1=CC=CC=N1 UEEXRMUCXBPYOV-UHFFFAOYSA-N 0.000 claims description 4
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 claims description 4
- 229940043267 rhodamine b Drugs 0.000 claims description 4
- 238000000926 separation method Methods 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 230000007613 environmental effect Effects 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 75
- 239000000243 solution Substances 0.000 description 54
- 238000000034 method Methods 0.000 description 39
- 239000012071 phase Substances 0.000 description 36
- 238000001228 spectrum Methods 0.000 description 34
- 239000008346 aqueous phase Substances 0.000 description 30
- 238000002390 rotary evaporation Methods 0.000 description 29
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 16
- 238000004293 19F NMR spectroscopy Methods 0.000 description 16
- 238000005160 1H NMR spectroscopy Methods 0.000 description 16
- TXNLQUKVUJITMX-UHFFFAOYSA-N 4-tert-butyl-2-(4-tert-butylpyridin-2-yl)pyridine Chemical compound CC(C)(C)C1=CC=NC(C=2N=CC=C(C=2)C(C)(C)C)=C1 TXNLQUKVUJITMX-UHFFFAOYSA-N 0.000 description 16
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 16
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 16
- 229910052799 carbon Inorganic materials 0.000 description 16
- 229910052731 fluorine Inorganic materials 0.000 description 16
- 239000011737 fluorine Substances 0.000 description 16
- 229910052739 hydrogen Inorganic materials 0.000 description 16
- 239000001257 hydrogen Substances 0.000 description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 150000002431 hydrogen Chemical class 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 238000006692 trifluoromethylation reaction Methods 0.000 description 5
- 239000002253 acid Substances 0.000 description 4
- DMVOXQPQNTYEKQ-UHFFFAOYSA-N biphenyl-4-amine Chemical group C1=CC(N)=CC=C1C1=CC=CC=C1 DMVOXQPQNTYEKQ-UHFFFAOYSA-N 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- RZXMPPFPUUCRFN-UHFFFAOYSA-N p-toluidine Chemical compound CC1=CC=C(N)C=C1 RZXMPPFPUUCRFN-UHFFFAOYSA-N 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- WCCVEGGNHCGFGB-UHFFFAOYSA-N C1[IH]C(C2=C1C=CC=C2)=O Chemical compound C1[IH]C(C2=C1C=CC=C2)=O WCCVEGGNHCGFGB-UHFFFAOYSA-N 0.000 description 3
- 230000003712 anti-aging effect Effects 0.000 description 3
- GPRYKVSEZCQIHD-UHFFFAOYSA-N 1-(4-aminophenyl)ethanone Chemical compound CC(=O)C1=CC=C(N)C=C1 GPRYKVSEZCQIHD-UHFFFAOYSA-N 0.000 description 2
- WKBALTUBRZPIPZ-UHFFFAOYSA-N 2,6-di(propan-2-yl)aniline Chemical compound CC(C)C1=CC=CC(C(C)C)=C1N WKBALTUBRZPIPZ-UHFFFAOYSA-N 0.000 description 2
- ZANPJXNYBVVNSD-UHFFFAOYSA-N 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(N)C=C1 ZANPJXNYBVVNSD-UHFFFAOYSA-N 0.000 description 2
- LNKBDFVSILQKSI-UHFFFAOYSA-N 4-Chloro-3-methoxyaniline Chemical compound COC1=CC(N)=CC=C1Cl LNKBDFVSILQKSI-UHFFFAOYSA-N 0.000 description 2
- XAGFYNSCWICYPA-UHFFFAOYSA-N 4-amino-n-methylbenzamide Chemical compound CNC(=O)C1=CC=C(N)C=C1 XAGFYNSCWICYPA-UHFFFAOYSA-N 0.000 description 2
- YBAZINRZQSAIAY-UHFFFAOYSA-N 4-aminobenzonitrile Chemical compound NC1=CC=C(C#N)C=C1 YBAZINRZQSAIAY-UHFFFAOYSA-N 0.000 description 2
- WDFQBORIUYODSI-UHFFFAOYSA-N 4-bromoaniline Chemical compound NC1=CC=C(Br)C=C1 WDFQBORIUYODSI-UHFFFAOYSA-N 0.000 description 2
- QSNSCYSYFYORTR-UHFFFAOYSA-N 4-chloroaniline Chemical compound NC1=CC=C(Cl)C=C1 QSNSCYSYFYORTR-UHFFFAOYSA-N 0.000 description 2
- KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 description 2
- VLVCDUSVTXIWGW-UHFFFAOYSA-N 4-iodoaniline Chemical compound NC1=CC=C(I)C=C1 VLVCDUSVTXIWGW-UHFFFAOYSA-N 0.000 description 2
- 244000144730 Amygdalus persica Species 0.000 description 2
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 2
- COHYTHOBJLSHDF-UHFFFAOYSA-N Indigo Chemical compound N1C2=CC=CC=C2C(=O)C1=C1C(=O)C2=CC=CC=C2N1 COHYTHOBJLSHDF-UHFFFAOYSA-N 0.000 description 2
- 235000006040 Prunus persica var persica Nutrition 0.000 description 2
- 239000005441 aurora Substances 0.000 description 2
- BLFLLBZGZJTVJG-UHFFFAOYSA-N benzocaine Chemical compound CCOC(=O)C1=CC=C(N)C=C1 BLFLLBZGZJTVJG-UHFFFAOYSA-N 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 2
- LRTFPLFDLJYEKT-UHFFFAOYSA-N para-isopropylaniline Chemical compound CC(C)C1=CC=C(N)C=C1 LRTFPLFDLJYEKT-UHFFFAOYSA-N 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- QKLXBIHSGMPUQS-FGZHOGPDSA-M (3r,5r)-7-[4-(4-fluorophenyl)-2,5-dimethyl-1-phenylpyrrol-3-yl]-3,5-dihydroxyheptanoate Chemical compound CC1=C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)C(C=2C=CC(F)=CC=2)=C(C)N1C1=CC=CC=C1 QKLXBIHSGMPUQS-FGZHOGPDSA-M 0.000 description 1
- VPMIAOSOTOODMY-KJAPKAAFSA-N (4r)-6-[(e)-2-[6-tert-butyl-4-(4-fluorophenyl)-2-propan-2-ylpyridin-3-yl]ethenyl]-4-hydroxyoxan-2-one Chemical compound C([C@H](O)C1)C(=O)OC1/C=C/C=1C(C(C)C)=NC(C(C)(C)C)=CC=1C1=CC=C(F)C=C1 VPMIAOSOTOODMY-KJAPKAAFSA-N 0.000 description 1
- QRDAPCMJAOQZSU-KQQUZDAGSA-N (e)-3-[4-[(e)-3-(3-fluorophenyl)-3-oxoprop-1-enyl]-1-methylpyrrol-2-yl]-n-hydroxyprop-2-enamide Chemical compound C1=C(\C=C\C(=O)NO)N(C)C=C1\C=C\C(=O)C1=CC=CC(F)=C1 QRDAPCMJAOQZSU-KQQUZDAGSA-N 0.000 description 1
- VGKYEIFFSOPYEW-UHFFFAOYSA-N 2-methyl-4-[(4-phenyldiazenylphenyl)diazenyl]phenol Chemical compound Cc1cc(ccc1O)N=Nc1ccc(cc1)N=Nc1ccccc1 VGKYEIFFSOPYEW-UHFFFAOYSA-N 0.000 description 1
- KLLLJCACIRKBDT-UHFFFAOYSA-N 2-phenyl-1H-indole Chemical compound N1C2=CC=CC=C2C=C1C1=CC=CC=C1 KLLLJCACIRKBDT-UHFFFAOYSA-N 0.000 description 1
- 239000002890 Aclonifen Substances 0.000 description 1
- REDUQXCPUSNJOL-UHFFFAOYSA-N C(C1=CC=CC=C1)NC(CN(C(C1=CC=C(C=C1)C(C)C)=O)CC1=CC=C(C=C1)C(NO)=O)=O Chemical compound C(C1=CC=CC=C1)NC(CN(C(C1=CC=C(C=C1)C(C)C)=O)CC1=CC=C(C=C1)C(NO)=O)=O REDUQXCPUSNJOL-UHFFFAOYSA-N 0.000 description 1
- CYSWUSAYJNCAKA-FYJFLYSWSA-N ClC1=C(C=CC=2N=C(SC=21)OCC)OC1=CC=C(C=N1)/C=C/[C@H](C)NC(C)=O Chemical compound ClC1=C(C=CC=2N=C(SC=21)OCC)OC1=CC=C(C=N1)/C=C/[C@H](C)NC(C)=O CYSWUSAYJNCAKA-FYJFLYSWSA-N 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- YLEIFZAVNWDOBM-ZTNXSLBXSA-N ac1l9hc7 Chemical compound C([C@H]12)C[C@@H](C([C@@H](O)CC3)(C)C)[C@@]43C[C@@]14CC[C@@]1(C)[C@@]2(C)C[C@@H]2O[C@]3(O)[C@H](O)C(C)(C)O[C@@H]3[C@@H](C)[C@H]12 YLEIFZAVNWDOBM-ZTNXSLBXSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- DDBMQDADIHOWIC-UHFFFAOYSA-N aclonifen Chemical compound C1=C([N+]([O-])=O)C(N)=C(Cl)C(OC=2C=CC=CC=2)=C1 DDBMQDADIHOWIC-UHFFFAOYSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- SRVFFFJZQVENJC-IHRRRGAJSA-N aloxistatin Chemical compound CCOC(=O)[C@H]1O[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)NCCC(C)C SRVFFFJZQVENJC-IHRRRGAJSA-N 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- POJOORKDYOPQLS-UHFFFAOYSA-L barium(2+) 5-chloro-2-[(2-hydroxynaphthalen-1-yl)diazenyl]-4-methylbenzenesulfonate Chemical compound [Ba+2].C1=C(Cl)C(C)=CC(N=NC=2C3=CC=CC=C3C=CC=2O)=C1S([O-])(=O)=O.C1=C(Cl)C(C)=CC(N=NC=2C3=CC=CC=C3C=CC=2O)=C1S([O-])(=O)=O POJOORKDYOPQLS-UHFFFAOYSA-L 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 1
- 229960005274 benzocaine Drugs 0.000 description 1
- KSCRVOKQPYZBHZ-IXPOFIJOSA-N benzyl n-[(2s)-1-[[(2s)-1-[[(2s)-1-(1,3-benzothiazol-2-yl)-1-oxo-3-[(3s)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C[C@H]1C(NCC1)=O)C(=O)C=1SC2=CC=CC=C2N=1)C(C)C)C(=O)OCC1=CC=CC=C1 KSCRVOKQPYZBHZ-IXPOFIJOSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- DSARWKALPGYFTA-UHFFFAOYSA-L disodium 4-hydroxy-7-[(5-hydroxy-6-phenyldiazenyl-7-sulfonatonaphthalen-2-yl)carbamoylamino]-3-phenyldiazenylnaphthalene-2-sulfonate Chemical compound [Na+].[Na+].[O-]S(=O)(=O)C1=CC2=CC(NC(=O)NC=3C=C4C=C(C(N=NC=5C=CC=CC=5)=C(O)C4=CC=3)S([O-])(=O)=O)=CC=C2C(O)=C1N=NC1=CC=CC=C1 DSARWKALPGYFTA-UHFFFAOYSA-L 0.000 description 1
- MCPLVIGCWWTHFH-UHFFFAOYSA-M disodium;4-[4-[[4-(4-sulfoanilino)phenyl]-[4-(4-sulfonatophenyl)azaniumylidenecyclohexa-2,5-dien-1-ylidene]methyl]anilino]benzenesulfonate Chemical compound [Na+].[Na+].C1=CC(S(=O)(=O)O)=CC=C1NC1=CC=C(C(=C2C=CC(C=C2)=[NH+]C=2C=CC(=CC=2)S([O-])(=O)=O)C=2C=CC(NC=3C=CC(=CC=3)S([O-])(=O)=O)=CC=2)C=C1 MCPLVIGCWWTHFH-UHFFFAOYSA-M 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 238000007336 electrophilic substitution reaction Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 239000010408 film Substances 0.000 description 1
- IYWCBYFJFZCCGV-UHFFFAOYSA-N formamide;hydrate Chemical compound O.NC=O IYWCBYFJFZCCGV-UHFFFAOYSA-N 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- LZXXNPOYQCLXRS-UHFFFAOYSA-N methyl 4-aminobenzoate Chemical compound COC(=O)C1=CC=C(N)C=C1 LZXXNPOYQCLXRS-UHFFFAOYSA-N 0.000 description 1
- QAPTWHXHEYAIKG-RCOXNQKVSA-N n-[(1r,2s,5r)-5-(tert-butylamino)-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](NC(C)(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 QAPTWHXHEYAIKG-RCOXNQKVSA-N 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 239000012860 organic pigment Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- MFOUDYKPLGXPGO-UHFFFAOYSA-N propachlor Chemical compound ClCC(=O)N(C(C)C)C1=CC=CC=C1 MFOUDYKPLGXPGO-UHFFFAOYSA-N 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- ANRHNWWPFJCPAZ-UHFFFAOYSA-M thionine Chemical compound [Cl-].C1=CC(N)=CC2=[S+]C3=CC(N)=CC=C3N=C21 ANRHNWWPFJCPAZ-UHFFFAOYSA-M 0.000 description 1
- 239000002966 varnish Substances 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/68—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton
- C07C209/74—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton by halogenation, hydrohalogenation, dehalogenation, or dehydrohalogenation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/08—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C221/00—Preparation of compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/16—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions not involving the amino or carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/025—Boronic and borinic acid compounds
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
A preparation method of trifluoromethylated aniline compounds shown in formula (IIA) or formula (IIB), which comprises the following steps: taking a DMF (dimethyl formamide) and water mixed solvent with a volume ratio of 1: 1-4 as a reaction medium, adding an aniline compound shown as a formula (IA) or a formula (IB), 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -ketone and a photocatalyst, reacting for 2-6H at room temperature under blue light, and after the reaction is completed, carrying out post-treatment on the obtained reaction mixture to obtain the trifluoromethylated aniline compound shown as a formula (IIA) or a formula (IIB). The invention utilizes the photocatalyst to drive the reaction to proceed under the irradiation of visible light, has mild reaction conditions, high site selectivity, high reaction efficiency, greenness and environmental protection, has the reaction yield of 90 percent, and can prepare the product by only one step.
Description
(I) technical field
The invention belongs to the technical field of organic chemistry, and particularly relates to a preparation method of trifluoromethylated aniline compounds, in particular to a novel method for preparing trifluoromethylated aniline compounds by directly trifluoromethylating aniline compounds.
(II) background of the invention
Aniline is an important basic organic raw material, has multiple purposes, and can be used for manufacturing acid ink blue G, acid medium BS, acid bright yellow, direct orange S, direct peach red, indigo blue, disperse yellow brown, cation peach red FG, reactive brilliant red X-SB and the like in the dye industry; the organic pigment is used for manufacturing aurora red, aurora red g, scarlet powder, phenol cyanine red, oil-soluble black and the like. In the printing and dyeing industry for the dye nigrosine; in the agrochemical industry for the production of many insecticides, fungicides such as DDV, aclonifen, propachlor and the like; aniline is an important raw material of rubber auxiliaries and is used for preparing an anti-aging agent A, an anti-aging agent D, an anti-aging agent 4010, accelerators M, 808, D, CA and the like; can also be used as raw material of sulfa drugs, and is also an intermediate for producing spices, plastics, varnish, films and the like; and can be used as a stabilizer in explosives, an explosion-proof agent in gasoline and a solvent; other compounds may also be used for the production of hydroquinone, 2-phenylindole, and the like.
Despite widespread use in organic synthesis, C-H bond trifluoromethylation of free anilines remains a significant challenge. The reason is that since nitrogen atoms have high nucleophilicity, free anilines are susceptible to electrophilic substitution, oxidation and even decomposition under harsh conditions, and lack an efficient and straightforward process, N-protected anilines are commonly used to attach CF3 groups and avoid the formation of by-products. However, the introduction and subsequent removal of protecting groups not only requires additional operations, such as removal of protecting groups under strongly acidic or basic reaction conditions (Piv, Ac, Boc, etc.), but also significantly reduces the compatibility of the functional groups, since many important functional groups are sensitive to acids and bases, and furthermore, the introduction of direct groups reduces atom economy. Undoubtedly, the most attractive and desirable route for trifluoromethylated free anilines is direct trifluoromethylation of the C-H bond of the free aniline. Therefore, it is of great significance and urgency to develop a novel and effective C-H trifluoromethylation method of aniline under mild conditions.
Disclosure of the invention
In order to overcome the defects and shortcomings of the existing aniline trifluoromethylation method, the invention provides a method for preparing trifluoromethylated aniline compounds by using a photocatalyst.
In order to achieve the purpose, the invention adopts the following technical scheme:
the invention provides a preparation method of trifluoromethylated aniline compounds shown in formula (IIA), which comprises the following steps: taking a DMF (dimethyl formamide) and water mixed solvent with a volume ratio of 1: 1-4 as a reaction medium, adding an aniline compound shown in formula (IA), 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -ketone and a photocatalyst, reacting for 2-6H at room temperature under blue light (usually an LED (light-emitting diode) lamp), and after the reaction is completed, carrying out post-treatment on the obtained reaction mixture to obtain a trifluoromethylated aniline compound shown in formula (IIA);
wherein R in the formula (IA) and the formula (IIA)2When it is methoxy, R1Is halogen; or R2When is H, R1Is C1-C3Alkyl, halogen, cyano, methoxy, acetyl, boroester, phenyl, -COOCH3、-COOC2H5or-COONHCH3；
The volume of the mixed solvent is 10mL/mmol based on the mass of the aniline compound shown in the formula (IA); the photocatalyst is tris (2,2' -bipyridyl) ruthenium dichloride, eosin Y, tris (2-phenylpyridine) iridium, fluorescein or rhodamine B; the mass ratio of the aniline compound shown in the formula (IA), the 1- (trifluoromethyl) -1, 2-phenyliodosyl-3 (1H) -ketone and the photocatalyst is 1: 1-3: 0.01-0.5.
Preferably, the trifluoromethylated aniline compound shown in the formula (IIA) is one of the following compounds:
preferably, the photocatalyst is fluorescein.
Further, the post-treatment comprises the following steps: adding saturated NaCl aqueous solution and ethyl acetate into the reaction mixture in sequence for extraction, collecting an organic layer after primary extraction, adding ethyl acetate into a water phase layer again for secondary extraction, combining the organic layers after the extraction is finished, drying and filtering the organic layers by anhydrous sodium sulfate, taking filtrate, and rotationally evaporating the solvent at normal temperature to obtain a crude product; and (3) performing silica gel column chromatography on the crude product, wherein the volume ratio is 1: and (3) taking a mixed solution of ethyl acetate and petroleum ether of 1-15 as an eluent, carrying out column chromatography separation, collecting a eluent containing a target product, removing the solvent under reduced pressure, and drying to obtain the trifluoromethylated aniline compound shown in the formula (IIA).
The invention also provides a preparation method of the trifluoromethylated aniline compound shown in the formula (IIB), which comprises the following steps: taking a DMF (dimethyl formamide) and water mixed solvent with a volume ratio of 1: 1-4 as a reaction medium, adding an aniline compound shown in formula (IB), 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -ketone and a photocatalyst, reacting for 2-6H at a room temperature under blue light, and after the reaction is completed, carrying out aftertreatment on the obtained reaction mixture to obtain a trifluoromethylated aniline compound shown in formula (IIB);
wherein in the formulae (IB) and (IIB), R3Is C1-C3An alkyl group;
the volume of the mixed solution is 10mL/mmol based on the mass of the aniline compound shown in the formula (IB); the photocatalyst is tris (2,2' -bipyridyl) ruthenium dichloride, eosin Y, tris (2-phenylpyridine) iridium, fluorescein or rhodamine B; the mass ratio of the aniline compound shown in the formula (IB), the 1- (trifluoromethyl) -1, 2-phenyliodosyl-3 (1H) -ketone and the photocatalyst is 1: 1-3: 0.01-0.5.
Preferably, the trifluoromethylated aniline compound represented by the formula (IIB) is
Preferably, the photocatalyst is fluorescein.
Further, the post-treatment comprises the following steps: adding saturated NaCl aqueous solution and ethyl acetate into the reaction mixture in sequence for extraction, collecting an organic layer after primary extraction, adding ethyl acetate into a water phase layer again for extraction, combining the organic layers after extraction is finished, drying and filtering the organic layers through anhydrous sodium sulfate, taking filtrate, and rotationally evaporating the solvent at normal temperature to obtain a crude product; and (3) performing silica gel column chromatography on the crude product, wherein the volume ratio is 1: and (2) taking a mixed solution of ethyl acetate and petroleum ether of 1-15 as an eluent, carrying out column chromatography separation, collecting a eluent containing a target product, and removing the solvent under reduced pressure to obtain the trifluoromethylated aniline compound shown in the formula (IIA) or the formula (IIB).
Compared with the prior art, the invention has the beneficial effects that: the invention provides a preparation method of trifluoromethylated aniline derivatives, which utilizes a photocatalyst to drive reaction under the irradiation of visible light, wherein the reaction solvent is a mixed solvent of water and DMF, and has the advantages of good catalytic performance, mild reaction conditions, high site selectivity and high reaction efficiency, and the reaction solvent is more in line with the green chemical concept advocated by modern chemistry, is green and environment-friendly, has the reaction yield of 90 percent, can prepare products by only one step, has simple operation process, is easily obtained by commercialization of raw materials, and is more direct, green, environment-friendly, efficient and rapid compared with the traditional aniline trifluoromethylation reaction method.
(IV) accompanying drawings
FIGS. 1,2 and 3 are nuclear magnetic diagrams of the hydrogen spectrum, carbon spectrum and fluorine spectrum of the compound 2a in example 1, respectively;
FIGS. 4, 5 and 6 are nuclear magnetic diagrams of the hydrogen spectrum, the carbon spectrum and the fluorine spectrum of the compound 2b in example 5, respectively;
FIGS. 7, 8 and 9 are nuclear magnetic diagrams of the hydrogen spectrum, the carbon spectrum and the fluorine spectrum of the compound 2c in example 9, respectively;
FIGS. 10, 11 and 12 are nuclear magnetic diagrams of the hydrogen spectrum, the carbon spectrum and the fluorine spectrum of the compound 2d in example 13, respectively;
FIGS. 13, 14 and 15 are nuclear magnetic maps of the hydrogen, carbon and fluorine spectra, respectively, of Compound 2e in example 17;
FIGS. 16, 17 and 18 are nuclear magnetic maps of the hydrogen, carbon and fluorine spectra, respectively, of Compound 2f in example 21;
FIGS. 19, 20 and 21 are nuclear magnetic maps of the hydrogen, carbon and fluorine spectra, respectively, of compound 2g in example 25;
FIGS. 22, 23 and 24 are nuclear magnetic maps of the hydrogen, carbon and fluorine spectra, respectively, of compound 2h in example 29;
FIGS. 25, 26 and 27 are nuclear magnetic maps of the hydrogen spectrum, carbon spectrum and fluorine spectrum, respectively, of Compound 2i in example 33;
FIGS. 28, 29 and 30 are nuclear magnetic maps of the hydrogen spectrum, carbon spectrum and fluorine spectrum, respectively, of Compound 2j in example 37;
FIGS. 31, 32 and 33 are nuclear magnetic maps of the hydrogen, carbon and fluorine spectra, respectively, of Compound 2k in example 41;
FIGS. 34, 35 and 36 are nuclear magnetic maps of the hydrogen, carbon and fluorine spectra, respectively, of Compound 2l of example 45;
FIGS. 37, 38 and 39 are nuclear magnetic maps of the hydrogen spectrum, carbon spectrum and fluorine spectrum, respectively, of Compound 2m in example 49;
FIGS. 40, 41 and 42 are nuclear magnetic maps of the hydrogen spectrum, carbon spectrum and fluorine spectrum, respectively, of Compound 2n in example 53;
FIGS. 43, 44 and 45 are nuclear magnetic maps of the hydrogen, carbon and fluorine spectra, respectively, of Compound 2o in example 57;
FIGS. 46, 47 and 48 are nuclear magnetic maps of the hydrogen spectrum, carbon spectrum and fluorine spectrum of Compound 2p in example 61, respectively.
(V) detailed description of the preferred embodiments
The invention will be further described with reference to specific examples, but the scope of the invention is not limited thereto:
the yields in the following examples are calculated according to the formula "yield, i.e. pure mass", actual yield/theoretical yield, which means moles of aniline substrate charged x molecular weight of the product.
Example 1:
21.4mg (0.2mmol) of 4-methylaniline was added to 2ml of a mixed solvent of DMF and water (the volume ratio of DMF to water was 1:4), 75.8mg (0.24mmol) of 1- (trifluoromethyl) -1, 2-benziodo-3 (1H) -one and 1.33mg (0.004mmol) of fluorescein were added thereto, and reacted under irradiation of a 9W blue LED lamp at normal temperature for 2 hours, and after the reaction was completed, an extraction operation was carried out: 1. and (3) adding a saturated NaCl aqueous solution and ethyl acetate into the reaction solution in sequence for extraction twice, 2, adding 50mL of the saturated NaCl aqueous solution and 25mL of ethyl acetate for the first time for primary extraction, 3, collecting an organic layer after the primary extraction is finished, adding 25mL of ethyl acetate into the aqueous phase layer again for secondary extraction, drying the organic layer by anhydrous sodium sulfate after the extraction is finished, filtering, taking the filtrate, and evaporating to dryness at normal temperature under reduced pressure to obtain a crude compound. And (3) performing silica gel column chromatography on the crude compound, taking a solution with the volume ratio of ethyl acetate to petroleum ether being 1:15 as a mobile phase, tracking and collecting an eluent with the Rf value of 0.5 by TLC, removing the solvent from the collected eluent by rotary evaporation at normal temperature under reduced pressure, and drying to obtain 31.2mg of a pure compound shown in the formula 2a, wherein the reaction yield is 89%.1H NMR(500MHz,CDCl3)6.83(dd,J＝12.0,1.2Hz,1H),6.78–6.74(m,1H),6.73–6.67(m,1H),3.59(s,2H),2.26(s,3H).13C NMR(126MHz,CDCl3)152.61(s),150.72(s),131.67(d,J＝13.0Hz),128.68(d,J＝6.5Hz),124.75(d,J＝3.1Hz),116.94(d,J＝3.9Hz),115.82(d,J＝18.4Hz),20.39(d,J＝1.2Hz).19F NMR(376MHz,CDCl3)-62.47(s).
Example 2:
the procedure was carried out in the same manner as in example 1 except that the mass and mole of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one was changed to 63.2mg (0.2mmol) and the mass and mole of fluorescein were changed to 0.664mg (0.002mmol), whereby 14mg of the pure compound represented by the formula 2a was obtained in a reaction yield of 40%.
Example 3:
the procedure was carried out in the same manner as in example 1 except that the mass and mole of 1- (trifluoromethyl) -1, 2-benziodoxyl-3 (1H) -one were changed to 189.6mg (0.6mmol) and the mass and mole of fluorescein were changed to 33.2mg (0.1mmol), whereby 23.4mg of the pure compound represented by the formula 2a was obtained in a reaction yield of 67%.
Example 4:
21.4mg (0.2mmol) of 4-methylaniline was added to 2ml of a mixed solvent of DMF and water (DMF/water volume ratio of 1:4), and 75.8mg (0.24mmol) of 1- (trifluoromethyl) -1, 2-benziodo-3 (1H) -one, 3.65mg (0.004mmol) of [ Ir (dtbbpy) ((ppy))2][PF6]And reacting for 2 hours under the irradiation of a 9W blue light LED lamp at normal temperature, and after the reaction is finished, carrying out extraction operation: 1. and (3) adding a saturated NaCl aqueous solution and ethyl acetate into the reaction solution in sequence for extraction twice, 2, adding 50mL of the saturated NaCl aqueous solution and 25mL of ethyl acetate for the first time for primary extraction, 3, collecting an organic layer after the primary extraction is finished, adding 25mL of ethyl acetate into the aqueous phase layer again for secondary extraction, drying the organic layer by anhydrous sodium sulfate after the extraction is finished, filtering, taking the filtrate, and evaporating to dryness at normal temperature under reduced pressure to obtain a crude compound. Subjecting the crude compound to silica gel column chromatography, collecting eluate with Rf of 0.5 by TLC with ethyl acetate and petroleum ether at a volume ratio of 1:15 as mobile phase, evaporating under reduced pressure at room temperature to remove solvent, and drying to obtain pure compound of formula 2a 3.5mg with reaction yield of 10%
Example 5:
43.8mg (0.2mmol) of 4-iodoaniline was added to 2ml of a mixed solvent of DMF and water (the volume ratio of DMF to water was 1:4), 75.8mg (0.24mmol) of 1- (trifluoromethyl) -1, 2-benziodol-3 (1H) -one and 1.33mg (0.004mmol) of fluorescein were added thereto, and the mixture was reacted at room temperature under irradiation of a 9W blue LED lamp for 4 hours, followed by extraction: 1. and (3) adding a saturated NaCl aqueous solution and ethyl acetate into the reaction solution in sequence for extraction twice, 2, adding 50mL of the saturated NaCl aqueous solution and 25mL of ethyl acetate for the first time for primary extraction, 3, collecting an organic layer after the primary extraction is finished, adding 25mL of ethyl acetate into the aqueous phase layer again for secondary extraction, drying the organic layer by anhydrous sodium sulfate after the extraction is finished, filtering, taking the filtrate, and evaporating to dryness at normal temperature under reduced pressure to obtain a crude compound. And (3) performing silica gel column chromatography on the crude compound, wherein the volume ratio of ethyl acetate to petroleum ether is 1: the solution of 10 is a mobile phase, an eluent with Rf value of 0.3 is collected by TLC tracking, the solvent is removed by rotary evaporation at normal temperature and reduced pressure after the collected eluent, and the pure compound shown as the formula 2b is obtained after drying, namely 51.7mg of the pure compound shown as the formula 2b is obtained, and the reaction yield is 90%.1H NMR(600MHz,CDCl3)7.71(d,J＝1.8Hz,1H),7.55(dd,J＝8.6,1.7Hz,1H),6.54(d,J＝8.6Hz,1H),4.37–4.10(m,2H).13C NMR(101MHz,CDCl3)144.10(s),141.34(s),134.91(q,J＝5.4Hz),125.17(s),122.46(s),119.11(s),115.89(s),.19F NMR(376MHz,CDCl3)-63.17(s).
Example 6:
the procedure was carried out in the same manner as in example 5 except that the mass and mole of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one was changed to 63.2mg (0.2mmol) and the mass and mole of fluorescein were changed to 0.664mg (0.002mmol), whereby 24mg of a pure compound represented by the formula 2b was obtained in a reaction yield of 42%.
Example 7:
the procedure was carried out in the same manner as in example 5 except that the mass and mole of 1- (trifluoromethyl) -1, 2-benziodoxyl-3 (1H) -one were changed to 189.6mg (0.6mmol) and the mass and mole of fluorescein were changed to 33.2mg (0.1mmol), whereby 32mg of the pure compound represented by the formula 2b was obtained in a reaction yield of 57%.
Example 8:
43.8mg (0.2mmol) of 4-iodoaniline was added to 2ml of a mixed solvent of DMF and water (DMF/water volume ratio of 1:4), and 75.8mg (0.24mmol) of 1- (trifluoromethyl) -1, 2-benziodo-3 (1H) -one, 3.65mg (0.004mmol) of [ Ir (dtbbpy) (ppy)2][PF6]And reacting for 4 hours under the irradiation of a 9W blue light LED lamp at normal temperature, and after the reaction is finished, carrying out extraction operation: 1. and (3) adding a saturated NaCl aqueous solution and ethyl acetate into the reaction solution in sequence for extraction twice, 2, adding 50mL of the saturated NaCl aqueous solution and 25mL of ethyl acetate for the first time for primary extraction, 3, collecting an organic layer after the primary extraction is finished, adding 25mL of ethyl acetate into the aqueous phase layer again for secondary extraction, drying the organic layer by anhydrous sodium sulfate after the extraction is finished, filtering, taking the filtrate, and evaporating to dryness at normal temperature under reduced pressure to obtain a crude compound. And (3) performing silica gel column chromatography on the crude compound, wherein the volume ratio of ethyl acetate to petroleum ether is 1: the solution of 10 is a mobile phase, an eluent with Rf value of 0.3 is collected by TLC tracking, the solvent is removed by rotary evaporation at normal temperature and reduced pressure after the collected eluent, and the pure compound shown as the formula 2b is obtained by drying, wherein the pure compound is 5.72mg, and the reaction yield is 10%.
Example 9:
34.2mg (0.2mmol) of 4-bromoaniline was added to 2ml of a mixed solvent of DMF and water (the volume ratio of DMF to water was 1:4), 75.8mg (0.24mmol) of 1- (trifluoromethyl) -1, 2-benziodo-3 (1H) -one and 1.33mg (0.004mmol) of fluorescein were added thereto, and the mixture was reacted at room temperature under irradiation of a 9W blue LED lamp for 4 hours, followed by extraction: 1. adding saturated NaCl aqueous solution and ethyl acetate into the reaction solution in sequence for extraction twice, 2, adding saturated NaCl aqueous solution 50mL for the first time and ethyl acetate 25mL for the first time for extraction, 3, collecting an organic layer after the extraction is finished for the first timeAnd adding 25ml of ethyl acetate into the water phase layer again for secondary extraction, drying the organic layer by anhydrous sodium sulfate after the extraction is finished, filtering, and evaporating the filtrate under reduced pressure at normal temperature to obtain a crude compound. And (3) performing silica gel column chromatography on the crude compound, wherein the volume ratio of ethyl acetate to petroleum ether is 1: the solution of 13 is mobile phase, TLC tracking collects eluent with Rf value of 0.5, the collected eluent is removed solvent by rotary evaporation under reduced pressure at normal temperature, and drying is carried out, thus obtaining the pure compound 41.7mg shown in the formula 2c with the reaction yield of 87%.1H NMR(600MHz,CDCl3)7.55(d,J＝2.2Hz,1H),7.39(dd,J＝8.6,2.1Hz,1H),6.65(d,J＝8.7Hz,1H),4.36–4.07(m,2H).13C NMR(101MHz,CDCl3)143.51(s),135.62(s),130.03–128.16(m),125.35(s),122.64(s),118.75(s),108.92(s).19F NMR(376MHz,CDCl3)-63.21(s).
Example 10:
the procedure was carried out in the same manner as in example 9 except for changing the mass and mole of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one to 63.2mg (0.2mmol) and the mass and mole of fluorescein to 0.664mg (0.002mmol), thereby obtaining 16mg of a pure compound represented by the formula 2c with a reaction yield of 35%.
Example 11:
the procedure was carried out in the same manner as in example 9 except that the mass and mole of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one were changed to 189.6mg (0.6mmol) and the mass and mole of fluorescein were changed to 33.2mg (0.1mmol), whereby 19mg of the pure compound represented by the formula 2c was obtained in a reaction yield of 41%
Example 12:
34.2mg (0.2mmol) of 4-bromoaniline was added to 2ml of a mixed solvent of DMF and water (DMF/water volume ratio of 1:4), and 75.8mg (0.24mmol) of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one, 3.65mg (0.004mmol) of [ Ir (dtbbpy) (ppy)2][PF6]And reacting for 4 hours under the irradiation of a 9W blue light LED lamp at normal temperature, and after the reaction is finished, carrying out extraction operation: 1. adding saturated NaCl aqueous solution and ethyl acetate into the reaction solution in sequence for extraction twice, 2, adding saturated NaCl aqueous solution 50mL for the first time and ethyl acetate 25mL for the first time, and extracting for the first time, 3, extracting for the first timeAnd after extraction, collecting an organic layer, adding 25ml of ethyl acetate into the water phase layer again for secondary extraction, drying the organic layer by using anhydrous sodium sulfate, filtering, taking filtrate, and evaporating the filtrate under reduced pressure at normal temperature to obtain a crude compound. And (3) performing silica gel column chromatography on the crude compound, wherein the volume ratio of ethyl acetate to petroleum ether is 1: the solution of 13 is a mobile phase, an eluent with Rf value of 0.5 is collected by TLC tracking, the solvent is removed by rotary evaporation at normal temperature and reduced pressure after the collected eluent, and the pure compound shown as the formula 2c is obtained after drying, wherein the pure compound is 4.78mg, and the reaction yield is 10%.
Example 13:
adding 25.4mg (0.2mmol) of 4-chloroaniline into 2ml of a mixed solvent of DMF and water (the volume ratio of DMF to water is 1:4), adding 75.8mg (0.24mmol) of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one and 1.33mg (0.004mmol) of fluorescein, reacting for 5 hours under the irradiation of a 9W blue LED lamp at normal temperature, and after the reaction is finished, carrying out extraction operation: 1. and (3) adding a saturated NaCl aqueous solution and ethyl acetate into the reaction solution in sequence for extraction twice, 2, adding 50mL of the saturated NaCl aqueous solution and 25mL of ethyl acetate for the first time for primary extraction, 3, collecting an organic layer after the primary extraction is finished, adding 25mL of ethyl acetate into the aqueous phase layer again for secondary extraction, drying the organic layer by anhydrous sodium sulfate after the extraction is finished, filtering, taking the filtrate, and evaporating to dryness at normal temperature under reduced pressure to obtain a crude compound. And (3) performing silica gel column chromatography on the crude compound, wherein the volume ratio of ethyl acetate to petroleum ether is 1: the solution of 10 is a mobile phase, an eluent with Rf value of 0.5 is collected by TLC tracking, the solvent is removed by rotary evaporation at normal temperature and reduced pressure after the collected eluent, and the pure compound shown as the formula 2d is obtained by drying, wherein 32.4mg of the pure compound is obtained, and the reaction yield is 83%.1H NMR(600MHz,CDCl3)7.42(d,J＝2.4Hz,1H),7.28–7.25(m,1H),6.70(d,J＝8.7Hz,1H),4.19(s,2H).13C NMR(101MHz,CDCl3)143.06(s),132.78(s),126.35(d,J＝5.4Hz),125.45(s),122.35(s),118.44(s),114.64(s).19F NMR(376MHz,CDCl3)-63.23(s).
Example 14:
the procedure was carried out in the same manner as in example 13 except for changing the mass and mole of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one to 63.2mg (0.2mmol) and the mass and mole of fluorescein to 0.664mg (0.002mmol), thereby obtaining 12mg of a pure compound represented by the formula 2d with a reaction yield of 33%.
Example 15:
the procedure was carried out in the same manner as in example 13 except that the mass and mole of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one were changed to 189.6mg (0.6mmol) and the mass and mole of fluorescein were changed to 33.2mg (0.1mmol), whereby 17mg of a pure compound represented by the formula 2d was obtained in a reaction yield of 45%
Example 16:
25.4mg (0.2mmol) of 4-chloroaniline was added to 2ml of a mixed solvent of DMF and water (DMF/water volume ratio of 1:4), and 75.8mg (0.24mmol) of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one, 3.65mg (0.004mmol) of [ Ir (dtbbpy) (ppy)2][PF6]And reacting for 5 hours under the irradiation of a 9W blue light LED lamp at normal temperature, and after the reaction is finished, carrying out extraction operation: 1. and (3) adding a saturated NaCl aqueous solution and ethyl acetate into the reaction solution in sequence for extraction twice, 2, adding 50mL of the saturated NaCl aqueous solution and 25mL of ethyl acetate for the first time for primary extraction, 3, collecting an organic layer after the primary extraction is finished, adding 25mL of ethyl acetate into the aqueous phase layer again for secondary extraction, drying the organic layer by anhydrous sodium sulfate after the extraction is finished, filtering, taking the filtrate, and evaporating to dryness at normal temperature under reduced pressure to obtain a crude compound. And (3) performing silica gel column chromatography on the crude compound, wherein the volume ratio of ethyl acetate to petroleum ether is 1: the solution of 10 is a mobile phase, an eluent with Rf value of 0.5 is collected by TLC tracking, the solvent is removed by rotary evaporation at normal temperature and reduced pressure after the collected eluent, and the pure compound shown as the formula 2d is obtained by drying, wherein the pure compound is 3.9mg, and the reaction yield is 10%.
Example 17:
22.2mg (0.2mmol) of 4-fluoroaniline was added to 2ml of a mixed solvent of DMF and water (the volume ratio of DMF to water was 1:4), 75.8mg (0.24mmol) of 1- (trifluoromethyl) -1, 2-benziodo-3 (1H) -one and 1.33mg (0.004mmol) of fluorescein were added thereto, and the mixture was reacted at room temperature under irradiation of a 9W blue LED lamp for 6 hours, and after the reaction was completed, extraction operation was carried out: 1. and (3) adding a saturated NaCl aqueous solution and ethyl acetate into the reaction solution in sequence for extraction twice, 2, adding 50mL of the saturated NaCl aqueous solution and 25mL of ethyl acetate for the first time for primary extraction, 3, collecting an organic layer after the primary extraction is finished, adding 25mL of ethyl acetate into the aqueous phase layer again for secondary extraction, drying the organic layer by anhydrous sodium sulfate after the extraction is finished, filtering, taking the filtrate, and evaporating to dryness at normal temperature under reduced pressure to obtain a crude compound. And (3) performing silica gel column chromatography on the crude compound, wherein the volume ratio of ethyl acetate to petroleum ether is 1:15 as mobile phase, collecting eluent with Rf value of 0.5 by TLC tracking, removing solvent by rotary evaporation at room temperature under reduced pressure, and drying to obtain pure compound 27.9mg shown in formula 2e with reaction yield of 78%.1H NMR(400MHz,CDCl3)7.17(dd,J＝8.9,2.9Hz,1H),7.10–6.99(m,1H),6.71(dd,J＝8.9,4.4Hz,1H),4.06(s,2H).13C NMR(101MHz,CDCl3)156.08(s),153.73(s),140.79(d,J＝1.9Hz),125.43(s),122.73(s),120.60–119.43(m),118.48(s).19F NMR(376MHz,CDCl3)-63.35(s),-126.50(td,J＝8.3,4.5Hz).
Example 18:
the same procedures as in example 17 were repeated except for changing the mass and mole of 1- (trifluoromethyl) -1, 2-benziodol-3 (1H) -one to 63.2mg (0.2mmol) and the mass and mole of fluorescein to 0.664mg (0.002mmol), to obtain 5mg of a pure compound represented by the formula 2e in a reaction yield of 14%.
Example 19:
the procedure was carried out in the same manner as in example 17 except that the mass and mole of 1- (trifluoromethyl) -1, 2-benziodoxyl-3 (1H) -one were changed to 189.6mg (0.6mmol) and the mass and mole of fluorescein were changed to 33.2mg (0.1mmol), whereby 7mg of a pure compound represented by the formula 2e was obtained in a reaction yield of 20%.
Example 20:
22.2mg (0.2mmol) of 4-fluoroaniline was added to 2ml of a mixed solvent of DMF and water (DMF/water volume ratio of 1:4), and 75.8mg (0.24mmol) of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one, 3.65mg (0.004mmol) of [ Ir (dtbbpy) (ppy)2][PF6]And reacting for 6 hours under the irradiation of a 9W blue light LED lamp at normal temperature, and after the reaction is finished, carrying out extraction operation: 1. and (3) adding a saturated NaCl aqueous solution and ethyl acetate into the reaction solution in sequence for extraction twice, 2, adding 50mL of the saturated NaCl aqueous solution and 25mL of ethyl acetate for the first time for primary extraction, 3, collecting an organic layer after the primary extraction is finished, adding 25mL of ethyl acetate into the aqueous phase layer again for secondary extraction, drying the organic layer by anhydrous sodium sulfate after the extraction is finished, filtering, taking the filtrate, and evaporating to dryness at normal temperature under reduced pressure to obtain a crude compound. And (3) performing silica gel column chromatography on the crude compound, wherein the volume ratio of ethyl acetate to petroleum ether is 1:15 as mobile phase, collecting eluent with Rf value of 0.5 by TLC tracking, removing solvent by rotary evaporation at room temperature under reduced pressure, and drying to obtain pure compound of formula 2e 3.58mg with reaction yield of 10%.
Example 21:
23.6mg (0.2mmol) of 4-cyanoaniline was added to 2ml of a mixed solvent of DMF and water (the volume ratio of DMF to water was 1:4), 75.8mg (0.24mmol) of 1- (trifluoromethyl) -1, 2-benziodo-3 (1H) -one and 1.33mg (0.004mmol) of fluorescein were added thereto, and the mixture was reacted at room temperature under irradiation of a 9W blue LED lamp for 6 hours, followed by extraction: 1. and (3) adding a saturated NaCl aqueous solution and ethyl acetate into the reaction solution in sequence for extraction twice, 2, adding 50mL of the saturated NaCl aqueous solution and 25mL of ethyl acetate for the first time for primary extraction, 3, collecting an organic layer after the primary extraction is finished, adding 25mL of ethyl acetate into the aqueous phase layer again for secondary extraction, drying the organic layer by anhydrous sodium sulfate after the extraction is finished, filtering, taking the filtrate, and evaporating to dryness at normal temperature under reduced pressure to obtain a crude compound. Will combine withPerforming silica gel column chromatography on the crude product, wherein the volume ratio of ethyl acetate to petroleum ether is 1: and (3) taking the solution of the step (8) as a mobile phase, tracking and collecting an eluent with the Rf value of 0.5 by TLC, removing the solvent from the collected eluent by rotary evaporation at normal temperature under reduced pressure, and drying to obtain a pure compound product 28.6mg shown in the formula 2f, wherein the reaction yield is 77%.1H NMR(600MHz,CDCl3)7.75(s,1H),7.55(dd,J＝8.6,1.7Hz,1H),6.78(d,J＝8.6Hz,1H),4.72(s,2H).13C NMR(101MHz,CDCl3)147.82(s),136.22(s),131.58(d,J＝5.3Hz),122.35(s),118.62(s),117.09(s),100.13(s),29.70(s).19F NMR(376MHz,CDCl3)-63.60(s).
Example 22:
the procedure was carried out in the same manner as in example 21 except for changing the mass and mole of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one to 63.2mg (0.2mmol) and the mass and mole of fluorescein to 0.664mg (0.002mmol), thereby obtaining 3.7mg of a pure compound represented by the formula 2f in a reaction yield of 10%.
Example 23:
the procedure was carried out in the same manner as in example 21 except that the mass and mole of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one were changed to 189.6mg (0.6mmol) and the mass and mole of fluorescein were changed to 33.2mg (0.1mmol), whereby 7.8mg of a pure compound represented by the formula 2f was obtained in a reaction yield of 21%.
Example 24:
23.6mg (0.2mmol) of 4-cyanoaniline was added to 2ml of a mixed solvent of DMF and water (DMF/water volume ratio of 1:4), and 75.8mg (0.24mmol) of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one, 3.65mg (0.004mmol) of [ Ir (dtbbpy) (ppy)2][PF6]And reacting for 6 hours under the irradiation of a 9W blue light LED lamp at normal temperature, and after the reaction is finished, carrying out extraction operation: 1. adding saturated NaCl aqueous solution and ethyl acetate into the reaction solution in sequence for extraction twice, 2, adding 50mL saturated NaCl aqueous solution and 25mL ethyl acetate for the first time for primary extraction, 3, collecting an organic layer after the primary extraction is finished, adding 25mL ethyl acetate into the aqueous phase layer again for secondary extraction, drying the organic layer with anhydrous sodium sulfate, filtering, taking the filtrate, evaporating to dryness under reduced pressure at normal temperature,thus obtaining the crude compound. And (3) performing silica gel column chromatography on the crude compound, wherein the volume ratio of ethyl acetate to petroleum ether is 1: and (3) taking the solution of the step (8) as a mobile phase, tracking and collecting an eluent with the Rf value of 0.5 by TLC, removing the solvent from the collected eluent by rotary evaporation at normal temperature under reduced pressure, and drying to obtain a pure compound product 1.86mg shown in the formula 2f, wherein the reaction yield is 5%.
Example 25:
24.6mg (0.2mmol) of 4-methoxyaniline was added to 2ml of a mixed solvent of DMF and water (the volume ratio of DMF to water is 1:4), 75.8mg (0.24mmol) of 1- (trifluoromethyl) -1, 2-benziodo-3 (1H) -one and 1.33mg (0.004mmol) of fluorescein were added thereto, and the mixture was reacted for 6 hours under irradiation of a 9W blue LED lamp at normal temperature, and after the reaction was completed, extraction was carried out: 1. and (3) adding a saturated NaCl aqueous solution and ethyl acetate into the reaction solution in sequence for extraction twice, 2, adding 50mL of the saturated NaCl aqueous solution and 25mL of ethyl acetate for the first time for primary extraction, 3, collecting an organic layer after the primary extraction is finished, adding 25mL of ethyl acetate into the aqueous phase layer again for secondary extraction, drying the organic layer by anhydrous sodium sulfate after the extraction is finished, filtering, taking the filtrate, and evaporating to dryness at normal temperature under reduced pressure to obtain a crude compound. And (3) performing silica gel column chromatography on the crude compound, wherein the volume ratio of ethyl acetate to petroleum ether is 1: the solution of 10 is used as a mobile phase, an eluent with the Rf value of 0.5 is collected by TLC tracking, the solvent is removed by rotary evaporation at normal temperature and reduced pressure after the collected eluent, and the pure product of the compound shown in the formula 2g, 30.9mg, with the reaction yield of 81 percent, is obtained after drying.1H NMR(600MHz,CDCl3)8.17(d,J＝1.6Hz,1H),7.98(dd,J＝8.6,1.8Hz,1H),6.75(d,J＝8.6Hz,1H),4.61(s,2H),3.90(s,3H)13C NMR(101MHz,CDCl3)151.76(s),138.30(d,J＝1.8Hz),126.09(s),123.38(s),119.69(d,J＝1.0Hz),118.90(s),111.04(q,J＝5.4Hz),55.76(s).19F NMR(376MHz,CDCl3)-62.78(s).
Example 26:
the procedure was carried out in the same manner as in example 25 except for changing the mass and mole of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one to 63.2mg (0.2mmol) and the mass and mole of fluorescein to 0.664mg (0.002mmol), thereby obtaining 4.5mg of a pure compound represented by the formula 2g with a reaction yield of 12%.
Example 27:
the procedure was carried out in the same manner as in example 25 except for changing the mass and mole of 1- (trifluoromethyl) -1, 2-benziodoxyl-3 (1H) -one to 189.6mg (0.6mmol) and the mass and mole of fluorescein to 33.2mg (0.1mmol), thereby obtaining 7.6mg of the pure compound represented by the formula 2g in 20% yield.
Example 28:
24.6mg (0.2mmol) of 4-methoxyaniline was added to 2ml of a mixed solvent of DMF and water (DMF/water volume ratio of 1:4), and 75.8mg (0.24mmol) of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one, 3.65mg (0.004mmol) of [ Ir (dtbbpy) (ppy)2][PF6]And reacting for 6 hours under the irradiation of a 9W blue light LED lamp at normal temperature, and after the reaction is finished, carrying out extraction operation: 1. and (3) adding a saturated NaCl aqueous solution and ethyl acetate into the reaction solution in sequence for extraction twice, 2, adding 50mL of the saturated NaCl aqueous solution and 25mL of ethyl acetate for the first time for primary extraction, 3, collecting an organic layer after the primary extraction is finished, adding 25mL of ethyl acetate into the aqueous phase layer again for secondary extraction, drying the organic layer by anhydrous sodium sulfate after the extraction is finished, filtering, taking the filtrate, and evaporating to dryness at normal temperature under reduced pressure to obtain a crude compound. And (3) performing silica gel column chromatography on the crude compound, wherein the volume ratio of ethyl acetate to petroleum ether is 1: the solution of 10 is a mobile phase, an eluent with Rf value of 0.5 is collected by TLC tracking, the solvent is removed by rotary evaporation at normal temperature and reduced pressure after the collected eluent, and the pure product of the compound shown in the formula 2g is obtained by drying, wherein the pure product is 1.91mg, and the reaction yield is 5%.
Example 29:
27mg (0.2mmol) of 4-aminoacetophenone was added to 2ml of a mixed solvent of DMF and water (volume ratio of DMF to water: 1:4), 75.8mg (0.24mmol) of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one was added thereto,1.33mg (0.004mmol) of fluorescein, reacting for 6 hours under the irradiation of a 9W blue LED lamp at normal temperature, and after the reaction is finished, extracting: 1. and (3) adding a saturated NaCl aqueous solution and ethyl acetate into the reaction solution in sequence for extraction twice, 2, adding 50mL of the saturated NaCl aqueous solution and 25mL of ethyl acetate for the first time for primary extraction, 3, collecting an organic layer after the primary extraction is finished, adding 25mL of ethyl acetate into the aqueous phase layer again for secondary extraction, drying the organic layer by anhydrous sodium sulfate after the extraction is finished, filtering, taking the filtrate, and evaporating to dryness at normal temperature under reduced pressure to obtain a crude compound. And (3) performing silica gel column chromatography on the crude compound, wherein the volume ratio of ethyl acetate to petroleum ether is 1: the solution of 10 is a mobile phase, an eluent with Rf value of 0.5 is collected by TLC tracking, the solvent is removed by rotary evaporation at normal temperature and reduced pressure after the collected eluent, and the pure product of the compound shown in the formula 2h is obtained after drying, wherein 33.3mg of the pure product is obtained, and the reaction yield is 82%.1H NMR(600MHz,CDCl3)8.09(d,J＝1.7Hz,1H),7.94(dd,J＝8.6,1.9Hz,1H),6.77(d,J＝8.6Hz,1H),4.68(s,2H),2.55(s,3H).13C NMR(101MHz,CDCl3)195.52(s),148.39(s),133.23(s),128.30(q,J＝5.1Hz),126.97(s),125.81(s),123.11(s),116.36(s),26.05(s).19F NMR(376MHz,CDCl3)-63.03(s).
Example 30:
the procedure was carried out in the same manner as in example 29 except for changing the mass and mole of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one to 63.2mg (0.2mmol) and the mass and mole of fluorescein to 0.664mg (0.002mmol), thereby obtaining 6mg of a pure compound represented by the formula 2H with a reaction yield of 15%.
Example 31:
the procedure was carried out in the same manner as in example 29 except that the mass and mole of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one were changed to 189.6mg (0.6mmol) and the mass and mole of fluorescein were changed to 33.2mg (0.1mmol), to obtain 9.7mg of the pure compound represented by the formula 2H in 24% yield
Example 32:
27mg (0.2mmol) of 4-aminoacetophenone was added to 2ml of a mixed solvent of DMF and water (volume ratio of DMF to water 1:4), to which 75.8mg (0.24mmol) of 1- (trifluoromethyl) was added) -1, 2-Benzoiodoxy-3 (1H) -one, 3.65mg (0.004mmol) [ Ir (dtbbpy) ((ppy))2][PF6]And reacting for 6 hours under the irradiation of a 9W blue light LED lamp at normal temperature, and after the reaction is finished, carrying out extraction operation: 1. and (3) adding a saturated NaCl aqueous solution and ethyl acetate into the reaction solution in sequence for extraction twice, 2, adding 50mL of the saturated NaCl aqueous solution and 25mL of ethyl acetate for the first time for primary extraction, 3, collecting an organic layer after the primary extraction is finished, adding 25mL of ethyl acetate into the aqueous phase layer again for secondary extraction, drying the organic layer by anhydrous sodium sulfate after the extraction is finished, filtering, taking the filtrate, and evaporating to dryness at normal temperature under reduced pressure to obtain a crude compound. And (3) performing silica gel column chromatography on the crude compound, wherein the volume ratio of ethyl acetate to petroleum ether is 1: 10 as mobile phase, collecting eluate with Rf value of 0.5 by TLC tracking, removing solvent by rotary evaporation at room temperature under reduced pressure, and drying to obtain pure compound 4.06mg shown in formula 2h with reaction yield of 10%
Example 33:
43.8mg (0.2mmol) of 4-aminophenylboronic acid pinacol ester is added to 2ml of a mixed solvent of DMF and water (the volume ratio of DMF to water is 1:1), 75.8mg (0.24mmol) of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one and 1.33mg (0.004mmol) of fluorescein are added thereto, and the mixture is reacted for 6 hours under the irradiation of a 9W blue LED lamp at normal temperature, and after the reaction is finished, extraction operation is carried out: 1. and (3) adding a saturated NaCl aqueous solution and ethyl acetate into the reaction solution in sequence for extraction twice, 2, adding 50mL of the saturated NaCl aqueous solution and 25mL of ethyl acetate for the first time for primary extraction, 3, collecting an organic layer after the primary extraction is finished, adding 25mL of ethyl acetate into the aqueous phase layer again for secondary extraction, drying the organic layer by anhydrous sodium sulfate after the extraction is finished, filtering, taking the filtrate, and evaporating to dryness at normal temperature under reduced pressure to obtain a crude compound. And (3) performing silica gel column chromatography on the crude compound, wherein the volume ratio of ethyl acetate to petroleum ether is 1: 10 is mobile phase, TLC tracking collects eluent with Rf value of 0.5, collects eluent and rotates at normal temperatureThe solvent was removed by evaporation under reduced pressure, and the residue was dried to obtain 45.9mg of a pure compound represented by formula 2i in a reaction yield of 80%.1H NMR(600MHz,CDCl3)7.91(s,1H),7.73(d,J＝8.1Hz,1H),6.73(d,J＝8.1Hz,1H),4.37(s,2H),1.35(s,12H).13C NMR(101MHz,CDCl3)146.92(d,J＝1.7Hz),139.31(s),134.63–132.88(m),126.42(s),123.71(s),116.10(s),83.71(s),24.83(s).19F NMR(376MHz,CDCl3)-62.55(s).
Example 34:
the same procedures as in example 33 were repeated except for changing the mass and mole of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one to 63.2mg (0.2mmol) and the mass and mole of fluorescein to 0.664mg (0.002mmol), to obtain 6.8mg of a pure compound represented by the formula 2i in a reaction yield of 12%.
Example 35:
the procedure was carried out in the same manner as in example 33 except that the mass and mole of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one were changed to 189.6mg (0.6mmol) and the mass and mole of fluorescein were changed to 33.2mg (0.1mmol), whereby 14.3mg of a pure compound represented by the formula 2i was obtained in a reaction yield of 25%.
Example 36:
43.8mg (0.2mmol) of 4-aminobenzeneboronic acid pinacol ester was added to 2ml of a mixed solvent of DMF and water (the volume ratio of DMF to water was 1:1), and 75.8mg (0.24mmol) of 1- (trifluoromethyl) -1, 2-benziodo-3 (1H) -one, 3.65mg (0.004mmol) [ Ir (dtbbpy) (ppy)2][PF6]And reacting for 6 hours under the irradiation of a 9W blue light LED lamp at normal temperature, and after the reaction is finished, carrying out extraction operation: 1. and (3) adding a saturated NaCl aqueous solution and ethyl acetate into the reaction solution in sequence for extraction twice, 2, adding 50mL of the saturated NaCl aqueous solution and 25mL of ethyl acetate for the first time for primary extraction, 3, collecting an organic layer after the primary extraction is finished, adding 25mL of ethyl acetate into the aqueous phase layer again for secondary extraction, drying the organic layer by anhydrous sodium sulfate after the extraction is finished, filtering, taking the filtrate, and evaporating to dryness at normal temperature under reduced pressure to obtain a crude compound. And (3) performing silica gel column chromatography on the crude compound, wherein the volume ratio of ethyl acetate to petroleum ether is 1: 10 is mobile phase, and is collected by TLC tracingCollecting the eluate with Rf value of 0.5, rotary evaporating at room temperature under reduced pressure to remove solvent, and drying to obtain 2.87mg pure compound shown in formula 2i with reaction yield of 5%.
Example 37:
adding 33.8mg (0.2mmol) of 4-aminobiphenyl into 2ml of a mixed solvent of DMF and water (the volume ratio of DMF to water is 1:4), adding 75.8mg (0.24mmol) of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -ketone and 1.33mg (0.004mmol) of fluorescein, reacting for 6 hours under the irradiation of a 9W blue light LED lamp at normal temperature, and after the reaction is finished, carrying out extraction operation: 1. and (3) adding a saturated NaCl aqueous solution and ethyl acetate into the reaction solution in sequence for extraction twice, 2, adding 50mL of the saturated NaCl aqueous solution and 25mL of ethyl acetate for the first time for primary extraction, 3, collecting an organic layer after the primary extraction is finished, adding 25mL of ethyl acetate into the aqueous phase layer again for secondary extraction, drying the organic layer by anhydrous sodium sulfate after the extraction is finished, filtering, taking the filtrate, and evaporating to dryness at normal temperature under reduced pressure to obtain a crude compound. And (3) performing silica gel column chromatography on the crude compound, wherein the volume ratio of ethyl acetate to petroleum ether is 1: the solution of 10 is used as a mobile phase, an eluent with the Rf value of 0.5 is collected by TLC tracking, the solvent is removed by rotary evaporation at normal temperature and reduced pressure after the collected eluent, and the pure compound shown as the formula 2j is obtained by drying, wherein the pure compound is 37.4mg, and the reaction yield is 79%.1H NMR(600MHz,CDCl3)7.66(d,J＝1.9Hz,1H),7.56–7.50(m,3H),7.41(dd,J＝10.7,4.8Hz,2H),7.31(t,J＝7.4Hz,1H),6.81(d,J＝8.4Hz,1H),4.20(s,2H).13C NMR(101MHz,CDCl3)143.66(s),139.92(s),131.44(s),130.90(s),128.85(s),126.90(s),126.41(s),125.08(q,J＝5.2Hz),123.61(s),117.65(s),114.09(d,J＝29.9Hz).19F NMR(376MHz,CDCl3)-63.03(s).
Example 38:
the procedure was carried out in the same manner as in example 37 except for changing the mass and mole of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one to 63.2mg (0.2mmol) and the mass and mole of fluorescein to 0.664mg (0.002mmol), thereby obtaining 4.7mg of a pure compound represented by the formula 2j with a reaction yield of 10%.
Example 39:
the procedure was carried out in the same manner as in example 37 except for changing the mass and mole of 1- (trifluoromethyl) -1, 2-benziodoxyl-3 (1H) -one to 189.6mg (0.6mmol) and the mass and mole of fluorescein to 33.2mg (0.1mmol), thereby obtaining 6.1mg of a pure compound represented by the formula 2j with a reaction yield of 13%.
Example 40:
33.8mg (0.2mmol) of 4-aminobiphenyl was added to 2ml of a mixed solvent of DMF and water (DMF to water volume ratio of 1:4), and 75.8mg (0.24mmol) of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one, 3.65mg (0.004mmol) of [ Ir (dtbbpy) (ppy)2][PF6]And reacting for 6 hours under the irradiation of a 9W blue light LED lamp at normal temperature, and after the reaction is finished, carrying out extraction operation: 1. and (3) adding a saturated NaCl aqueous solution and ethyl acetate into the reaction solution in sequence for extraction twice, 2, adding 50mL of the saturated NaCl aqueous solution and 25mL of ethyl acetate for the first time for primary extraction, 3, collecting an organic layer after the primary extraction is finished, adding 25mL of ethyl acetate into the aqueous phase layer again for secondary extraction, drying the organic layer by anhydrous sodium sulfate after the extraction is finished, filtering, taking the filtrate, and evaporating to dryness at normal temperature under reduced pressure to obtain a crude compound. And (3) performing silica gel column chromatography on the crude compound, wherein the volume ratio of ethyl acetate to petroleum ether is 1: the solution of 10 is a mobile phase, an eluent with the Rf value of 0.5 is collected by TLC tracking, the solvent is removed by rotary evaporation at normal temperature and reduced pressure after the collected eluent, and the pure compound shown as the formula 2j is obtained after drying, wherein the pure compound is 4.74mg, and the reaction yield is 10%.
Example 41:
27mg (0.2mmol) of 4-isopropylaniline was added to 2ml of a mixed solvent of DMF and water (the volume ratio of DMF to water was 1:4), 75.8mg (0.24mmol) of 1- (trifluoromethyl) -1, 2-benziodo-3 (1H) -one and 1.33mg (0.004mmol) of fluorescein were added thereto, and blue light L of 9W was applied at ordinary temperatureAnd (3) reacting for 6 hours under the irradiation of an ED lamp, and after the reaction is finished, carrying out extraction operation: 1. and (3) adding a saturated NaCl aqueous solution and ethyl acetate into the reaction solution in sequence for extraction twice, 2, adding 50mL of the saturated NaCl aqueous solution and 25mL of ethyl acetate for the first time for primary extraction, 3, collecting an organic layer after the primary extraction is finished, adding 25mL of ethyl acetate into the aqueous phase layer again for secondary extraction, drying the organic layer by anhydrous sodium sulfate after the extraction is finished, filtering, taking the filtrate, and evaporating to dryness at normal temperature under reduced pressure to obtain a crude compound. And (3) performing silica gel column chromatography on the crude compound, wherein the volume ratio of ethyl acetate to petroleum ether is 1:15 is used as a mobile phase, an eluent with the Rf value of 0.5 is collected by TLC tracking, the solvent is removed by rotary evaporation and reduced pressure at normal temperature after the collected eluent, and the pure compound shown as the formula 2k is obtained by drying, wherein the pure compound is 30.4mg, and the reaction yield is 75%.1H NMR(600MHz,CDCl3)7.29(d,J＝1.8Hz,1H),7.19(dd,J＝8.3,1.8Hz,1H),6.71(d,J＝8.3Hz,1H),4.05(s,2H),2.86(dt,J＝13.8,6.9Hz,1H),1.24(d,J＝6.9Hz,6H).13C NMR(101MHz,CDCl3)142.29(s),138.36(s),130.96(s),126.47(s),124.08(q,J＝5.1Hz),123.77(s),123.77(s),33.12(s),24.00(s).19F NMR(376MHz,CDCl3)-62.47(s).
Example 42:
the procedure was carried out in the same manner as in example 41 except that the mass and mole of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one was changed to 63.2mg (0.2mmol) and the mass and mole of fluorescein were changed to 0.664mg (0.002mmol), whereby 4.4mg of a pure compound represented by the formula 2k was obtained in a reaction yield of 11%.
Example 43:
the procedure was carried out in the same manner as in example 41 except that the mass and mole of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one was changed to 189.6mg (0.6mmol) and the mass and mole of fluorescein were changed to 33.2mg (0.1mmol), whereby 9.7mg of a pure compound represented by the formula 2k was obtained in a reaction yield of 24%.
Example 44:
27mg (0.2mmol) of 4-isopropylaniline was added to 2ml of a mixed solvent of DMF and water (DMF/water volume ratio of 1:4), to which 75.8mg (0.24mmol) of 1- (trifluoromethyl) -1, 2-benzene was addedIodoyl-3 (1H) -one, 3.65mg (0.004mmol) [ Ir (dtbbpy) ((ppy))2][PF6]And reacting for 6 hours under the irradiation of a 9W blue light LED lamp at normal temperature, and after the reaction is finished, carrying out extraction operation: 1. and (3) adding a saturated NaCl aqueous solution and ethyl acetate into the reaction solution in sequence for extraction twice, 2, adding 50mL of the saturated NaCl aqueous solution and 25mL of ethyl acetate for the first time for primary extraction, 3, collecting an organic layer after the primary extraction is finished, adding 25mL of ethyl acetate into the aqueous phase layer again for secondary extraction, drying the organic layer by anhydrous sodium sulfate after the extraction is finished, filtering, taking the filtrate, and evaporating to dryness at normal temperature under reduced pressure to obtain a crude compound. And (3) performing silica gel column chromatography on the crude compound, wherein the volume ratio of ethyl acetate to petroleum ether is 1:15 is used as a mobile phase, an eluent with Rf value of 0.5 is collected by TLC tracking, the solvent is removed by rotary evaporation at normal temperature and reduced pressure after the collected eluent, and the pure compound shown as the formula 2k is obtained after drying, wherein the pure compound is 2.03mg, and the reaction yield is 5%.
Example 45:
30.2mg (0.2mmol) of 4-methyl aminobenzoate was added to 2ml of a mixed solvent of DMF and water (the volume ratio of DMF to water was 1:1), 75.8mg (0.24mmol) of 1- (trifluoromethyl) -1, 2-benziodol-3 (1H) -one and 1.33mg (0.004mmol) of fluorescein were added thereto, and reacted under irradiation of a 9W blue LED lamp at normal temperature for 6 hours, and after the reaction was completed, extraction was performed: 1. and (3) adding a saturated NaCl aqueous solution and ethyl acetate into the reaction solution in sequence for extraction twice, 2, adding 50mL of the saturated NaCl aqueous solution and 25mL of ethyl acetate for the first time for primary extraction, 3, collecting an organic layer after the primary extraction is finished, adding 25mL of ethyl acetate into the aqueous phase layer again for secondary extraction, drying the organic layer by anhydrous sodium sulfate after the extraction is finished, filtering, taking the filtrate, and evaporating to dryness at normal temperature under reduced pressure to obtain a crude compound. And (3) performing silica gel column chromatography on the crude compound, wherein the volume ratio of ethyl acetate to petroleum ether is 1: 5 is mobile phase, TLC tracking collects eluent with Rf value of 0.3, and the collected eluent is removed by rotary evaporation and reduced pressure at normal temperatureThen, the mixture was dried to obtain 33.2mg of a pure compound represented by the formula 2l, which was obtained in a reaction yield of 76%.1H NMR(600MHz,CDCl3)8.17(d,J＝1.6Hz,1H),7.98(dd,J＝8.6,1.8Hz,1H),6.75(d,J＝8.6Hz,1H),4.61(s,2H),3.90(s,3H).13C NMR(101MHz,CDCl3)166.15(s),148.22(s),134.28(s),129.17(q,J＝5.3Hz),125.80(s),123.10(s),119.17(s),116.29(s),51.92(s).19F NMR(376MHz,CDCl3)-63.05(s).
Example 46:
the procedure was carried out in the same manner as in example 45 except for changing the mass and mole of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one to 63.2mg (0.2mmol) and the mass and mole of fluorescein to 0.664mg (0.002mmol), thereby obtaining 4.3mg of a pure compound represented by the formula 2l with a reaction yield of 10%.
Example 47:
the procedure was carried out in the same manner as in example 45 except for changing the mass and mole of 1- (trifluoromethyl) -1, 2-benziodoxyl-3 (1H) -one to 189.6mg (0.6mmol) and the mass and mole of fluorescein to 33.2mg (0.1mmol), thereby obtaining 9.1mg of a pure compound represented by the formula 2l with a reaction yield of 21%.
Example 48:
30.2mg (0.2mmol) of methyl 4-aminobenzoate was added to 2ml of a mixed solvent of DMF and water (volume ratio of DMF to water 1:1), and 75.8mg (0.24mmol) of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one, 3.65mg (0.004mmol) [ Ir (dtbbpy) ((ppy))2][PF6]And reacting for 6 hours under the irradiation of a 9W blue light LED lamp at normal temperature, and after the reaction is finished, carrying out extraction operation: 1. and (3) adding a saturated NaCl aqueous solution and ethyl acetate into the reaction solution in sequence for extraction twice, 2, adding 50mL of the saturated NaCl aqueous solution and 25mL of ethyl acetate for the first time for primary extraction, 3, collecting an organic layer after the primary extraction is finished, adding 25mL of ethyl acetate into the aqueous phase layer again for secondary extraction, drying the organic layer by anhydrous sodium sulfate after the extraction is finished, filtering, taking the filtrate, and evaporating to dryness at normal temperature under reduced pressure to obtain a crude compound. And (3) performing silica gel column chromatography on the crude compound, wherein the volume ratio of ethyl acetate to petroleum ether is 1: 5 as mobile phase, and collecting Rf value by TLC tracing0.3, collecting the obtained eluent, removing the solvent by rotary evaporation at normal temperature under reduced pressure, and drying to obtain 2.19mg of a pure compound shown as a formula 2l, wherein the reaction yield is 5%.
Example 49:
adding 33mg (0.2mmol) of 4-ethyl aminobenzoate into 2ml of a mixed solvent of DMF and water (the volume ratio of DMF to water is 1:1), adding 75.8mg (0.24mmol) of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one and 1.33mg (0.004mmol) of fluorescein, reacting for 6 hours under the irradiation of a 9W blue light LED lamp at normal temperature, and after the reaction is finished, performing extraction operation: 1. and (3) adding a saturated NaCl aqueous solution and ethyl acetate into the reaction solution in sequence for extraction twice, 2, adding 50mL of the saturated NaCl aqueous solution and 25mL of ethyl acetate for the first time for primary extraction, 3, collecting an organic layer after the primary extraction is finished, adding 25mL of ethyl acetate into the aqueous phase layer again for secondary extraction, drying the organic layer by anhydrous sodium sulfate after the extraction is finished, filtering, taking the filtrate, and evaporating to dryness at normal temperature under reduced pressure to obtain a crude compound. And (3) performing silica gel column chromatography on the crude compound, wherein the volume ratio of ethyl acetate to petroleum ether is 1: the solution 1 is a mobile phase, an eluent with Rf value of 0.3 is collected by TLC tracking, the solvent is removed by rotary evaporation at normal temperature and reduced pressure after the collected eluent, and the pure compound 31.2mg shown in the formula 2m is obtained after drying, and the reaction yield is 67%.1H NMR(400MHz,CDCl3)8.16(d,J＝1.5Hz,1H),7.97(dd,J＝8.6,1.8Hz,1H),6.74(d,J＝8.6Hz,1H),4.66(s,2H),4.35(q,J＝7.1Hz,2H),1.39(t,J＝7.1Hz,3H).13C NMR(101MHz,CDCl3)165.80(s),148.28(s),134.24(s),129.07(q,J＝5.2Hz),125.85(s),119.34(s),116.27(s),112.66(q,J＝30.7Hz),60.81(s),14.35(s).19F NMR(376MHz,CDCl3)-63.07(s).
Example 50:
the procedure was carried out in the same manner as in example 49 except for changing the mass and mole of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one to 63.2mg (0.2mmol) and the mass and mole of fluorescein to 0.664mg (0.002mmol), thereby obtaining 4.6mg of a pure compound represented by the formula 2m with a reaction yield of 10%.
Example 51:
the procedure was carried out in the same manner as in example 49 except for changing the mass and mole of 1- (trifluoromethyl) -1, 2-benziodoxyl-3 (1H) -one to 189.6mg (0.6mmol) and the mass and mole of fluorescein to 33.2mg (0.1mmol), thereby obtaining 9.3mg of a pure compound represented by the formula 2m with a reaction yield of 20%.
Example 52:
33mg (0.2mmol) of ethyl 4-aminobenzoate was added to 2ml of a mixed solvent of DMF and water (DMF to water volume ratio of 1:1), and 75.8mg (0.24mmol) of 1- (trifluoromethyl) -1, 2-benziodo-3 (1H) -one, 3.65mg (0.004mmol) of [ Ir (dtbbpy) ((ppy))2][PF6]And reacting for 6 hours under the irradiation of a 9W blue light LED lamp at normal temperature, and after the reaction is finished, carrying out extraction operation: 1. and (3) adding a saturated NaCl aqueous solution and ethyl acetate into the reaction solution in sequence for extraction twice, 2, adding 50mL of the saturated NaCl aqueous solution and 25mL of ethyl acetate for the first time for primary extraction, 3, collecting an organic layer after the primary extraction is finished, adding 25mL of ethyl acetate into the aqueous phase layer again for secondary extraction, drying the organic layer by anhydrous sodium sulfate after the extraction is finished, filtering, taking the filtrate, and evaporating to dryness at normal temperature under reduced pressure to obtain a crude compound. And (3) performing silica gel column chromatography on the crude compound, wherein the volume ratio of ethyl acetate to petroleum ether is 1: the solution 1 is a mobile phase, an eluent with the Rf value of 0.3 is collected by TLC tracking, the solvent is removed by rotary evaporation at normal temperature and reduced pressure after the collected eluent, and the pure compound 2.33mg shown in the formula 2m is obtained after drying, and the reaction yield is 10%.
Example 53:
35.4mg (0.2mmol) of 2, 6-diisopropylaniline was added to 2ml of a mixed solvent of DMF and water (volume ratio of DMF to water: 1:4), 75.8mg (0.24mmol) of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one, 1.33mg (0.004mmol) of fluorescein were added thereto, and a 9W blue LED was placed at room temperatureAnd (3) reacting for 6 hours under the irradiation of a lamp, and after the reaction is finished, carrying out extraction operation: 1. and (3) adding a saturated NaCl aqueous solution and ethyl acetate into the reaction solution in sequence for extraction twice, 2, adding 50mL of the saturated NaCl aqueous solution and 25mL of ethyl acetate for the first time for primary extraction, 3, collecting an organic layer after the primary extraction is finished, adding 25mL of ethyl acetate into the aqueous phase layer again for secondary extraction, drying the organic layer by anhydrous sodium sulfate after the extraction is finished, filtering, taking the filtrate, and evaporating to dryness at normal temperature under reduced pressure to obtain a crude compound. And (3) performing silica gel column chromatography on the crude compound, wherein the volume ratio of ethyl acetate to petroleum ether is 1: and (3) taking the solution of the step (8) as a mobile phase, tracking and collecting an eluent with the Rf value of 0.5 by TLC, removing the solvent from the collected eluent by rotary evaporation at normal temperature under reduced pressure, and drying to obtain a pure compound product 38.2mg shown in the formula 2n, wherein the reaction yield is 78%.1H NMR(600MHz,CDCl3)7.29(2H,s),4.04(2H,s),2.99–2.89(2H,m),1.32(12H,d,J 6.9).13C NMR(101MHz,CDCl3)143.34(s),131.88(s),122.78(s),120.00(dd,J＝7.5,3.7Hz),27.99(s),22.12(s).19F NMR(376MHz,CDCl3)-60.86(s).
Example 54:
the procedure was carried out in the same manner as in example 53 except for changing the mass and mole of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one to 63.2mg (0.2mmol) and the mass and mole of fluorescein to 0.664mg (0.002mmol), thereby obtaining 6.3mg of a pure compound represented by the formula 2n with a reaction yield of 13%.
Example 55:
the procedure was carried out in the same manner as in example 53 except for changing the mass and mole of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one to 189.6mg (0.6mmol) and the mass and mole of fluorescein to 33.2mg (0.1mmol), to obtain 9.3mg of a pure compound represented by the formula 2n with a reaction yield of 19%.
Example 56:
35.4mg (0.2mmol) of 2, 6-diisopropylaniline was added to 2ml of a mixed solvent of DMF and water (volume ratio of DMF to water: 1:4), to which 75.8mg (0.24mmol) of 1- (trifluoromethyl) -1, 2-phenyliodoxy-3 (1H) -one, 3.65mg (0.004mmol) of [ Ir (dtbbpy) ((ppy))2][PF6]At normal temperatureReacting for 6 hours under the irradiation of a 9W blue LED lamp, and after the reaction is finished, carrying out extraction operation: 1. and (3) adding a saturated NaCl aqueous solution and ethyl acetate into the reaction solution in sequence for extraction twice, 2, adding 50mL of the saturated NaCl aqueous solution and 25mL of ethyl acetate for the first time for primary extraction, 3, collecting an organic layer after the primary extraction is finished, adding 25mL of ethyl acetate into the aqueous phase layer again for secondary extraction, drying the organic layer by anhydrous sodium sulfate after the extraction is finished, filtering, taking the filtrate, and evaporating to dryness at normal temperature under reduced pressure to obtain a crude compound. And (3) performing silica gel column chromatography on the crude compound, wherein the volume ratio of ethyl acetate to petroleum ether is 1: and (3) taking the solution of the step (8) as a mobile phase, tracking and collecting an eluent with the Rf value of 0.5 by TLC, removing the solvent from the collected eluent by rotary evaporation at normal temperature under reduced pressure, and drying to obtain a pure compound product 2.45mg shown in the formula 2n, wherein the reaction yield is 5%.
Example 57:
adding 31.4mg (0.2mmol) of 3-methoxy-4-chloroaniline into 2ml of a mixed solvent of DMF and water (the volume ratio of DMF to water is 1:4), adding 75.8mg (0.24mmol) of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -ketone and 1.33mg (0.004mmol) of fluorescein, reacting for 6 hours under the irradiation of a 9W blue LED lamp at normal temperature, and after the reaction is finished, carrying out extraction operation: 1. and (3) adding a saturated NaCl aqueous solution and ethyl acetate into the reaction solution in sequence for extraction twice, 2, adding 50mL of the saturated NaCl aqueous solution and 25mL of ethyl acetate for the first time for primary extraction, 3, collecting an organic layer after the primary extraction is finished, adding 25mL of ethyl acetate into the aqueous phase layer again for secondary extraction, drying the organic layer by anhydrous sodium sulfate after the extraction is finished, filtering, taking the filtrate, and evaporating to dryness at normal temperature under reduced pressure to obtain a crude compound. And (3) performing silica gel column chromatography on the crude compound, wherein the volume ratio of ethyl acetate to petroleum ether is 1: the solution of 10 is used as a mobile phase, an eluent with the Rf value of 0.5 is collected by TLC tracking, the solvent is removed by rotary evaporation at normal temperature and reduced pressure after the collected eluent, and the pure compound shown as the formula 2o is obtained by drying, wherein the reaction yield is 60 percent.1H NMR(600MHz,DMSO)7.29(s,1H),6.56(s,1H),5.74(s,2H),3.80(s,3H).13C NMR(101MHz,DMSO)158.08(s),147.50(s),127.33(q,J＝5.2Hz),126.40(s),123.70(s),107.78(s),100.46(s),56.35(s).19F NMR(376MHz,DMSO)-60.30(s).
Example 58:
the procedure was carried out in the same manner as in example 57 except that the mass and mole of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one was changed to 63.2mg (0.2mmol) and the mass and mole of fluorescein were changed to 0.664mg (0.002mmol), whereby 9mg of a pure compound represented by the formula 2o was obtained in a reaction yield of 20%.
Example 59:
the procedure was carried out in the same manner as in example 57 except that the mass and mole of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one was changed to 189.6mg (0.6mmol) and the mass and mole of fluorescein were changed to 33.2mg (0.1mmol), whereby 11.7mg of a pure compound represented by the formula 2o was obtained in a reaction yield of 26%.
Example 60:
31.4mg (0.2mmol) of 3-methoxy-4-chloroaniline was added to 2ml of a mixed solvent of DMF and water (the volume ratio of DMF to water was 1:4), and 75.8mg (0.24mmol) of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one, 3.65mg (0.004mmol) of [ Ir (dtbbpy) (ppy)2][PF6]And reacting for 6 hours under the irradiation of a 9W blue light LED lamp at normal temperature, and after the reaction is finished, carrying out extraction operation: 1. and (3) adding a saturated NaCl aqueous solution and ethyl acetate into the reaction solution in sequence for extraction twice, 2, adding 50mL of the saturated NaCl aqueous solution and 25mL of ethyl acetate for the first time for primary extraction, 3, collecting an organic layer after the primary extraction is finished, adding 25mL of ethyl acetate into the aqueous phase layer again for secondary extraction, drying the organic layer by anhydrous sodium sulfate after the extraction is finished, filtering, taking the filtrate, and evaporating to dryness at normal temperature under reduced pressure to obtain a crude compound. And (3) performing silica gel column chromatography on the crude compound, wherein the volume ratio of ethyl acetate to petroleum ether is 1: the solution of 10 is a mobile phase, an eluent with Rf value of 0.5 is collected by TLC tracking, the solvent is removed by rotary evaporation at normal temperature and reduced pressure after the collected eluent, and the pure product of the compound shown in the formula 2o is obtained by drying, wherein the pure product is 2.25mg, and the reaction yield is 5%.
Example 61:
30mg (0.2mmol) of 4-amino-N-methylbenzamide was added to 2ml of a mixed solvent of DMF and water (the volume ratio of DMF to water was 1:4), 75.8mg (0.24mmol) of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one and 1.33mg (0.004mmol) of fluorescein were added thereto, and reacted under irradiation of a 9W blue LED lamp at normal temperature for 6 hours, and after the reaction was completed, extraction was carried out: 1. and (3) adding a saturated NaCl aqueous solution and ethyl acetate into the reaction solution in sequence for extraction twice, 2, adding 50mL of the saturated NaCl aqueous solution and 25mL of ethyl acetate for the first time for primary extraction, 3, collecting an organic layer after the primary extraction is finished, adding 25mL of ethyl acetate into the aqueous phase layer again for secondary extraction, drying the organic layer by anhydrous sodium sulfate after the extraction is finished, filtering, taking the filtrate, and evaporating to dryness at normal temperature under reduced pressure to obtain a crude compound. And (3) performing silica gel column chromatography on the crude compound, wherein the volume ratio of ethyl acetate to petroleum ether is 1: the solution 1 is a mobile phase, an eluent with the Rf value of 0.3 is collected by TLC tracking, the solvent is removed by rotary evaporation and reduced pressure at normal temperature after the collected eluent, and the pure compound shown in the formula 2p is obtained by drying, wherein the pure compound is 30.5mg, and the reaction yield is 70%.1H NMR(600MHz,CDCl3)7.88(s,1H),7.73(d,J＝8.3Hz,1H),6.72(d,J＝8.5Hz,1H),6.42(s,1H),4.61(s,2H),2.98(d,J＝4.8Hz,3H).13C NMR(101MHz,CDCl3)147.22(s),140.99(s),131.72(s),128.59(s),126.05(q,J＝5.2Hz),123.14(d,J＝5.8Hz),116.65(s),112.66(q,J＝30.5Hz),26.87(s).19F NMR(376MHz,CDCl3)-62.98(s).
Example 62:
the procedure was carried out in the same manner as in example 61 except for changing the mass and mole of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one to 63.2mg (0.2mmol) and the mass and mole of fluorescein to 0.664mg (0.002mmol), thereby obtaining 5.2mg of a pure compound represented by the formula 2p with a reaction yield of 12%.
Example 63:
the procedure was carried out in the same manner as in example 61 except that the mass and mole of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one was changed to 189.6mg (0.6mmol) and the mass and mole of fluorescein were changed to 33.2mg (0.1mmol), whereby 8.7mg of a pure compound represented by the formula 2p was obtained in a reaction yield of 20%.
Example 64:
30mg (0.2mmol) of 4-amino-N-methylbenzamide was added to 2ml of a mixed solvent of DMF and water (volume ratio of DMF to water: 1:4), and 75.8mg (0.24mmol) of 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -one, 3.65mg (0.004mmol) of [ Ir (dtbbpy) (ppy)2][PF6]And reacting for 6 hours under the irradiation of a 9W blue light LED lamp at normal temperature, and after the reaction is finished, carrying out extraction operation: 1. and (3) adding a saturated NaCl aqueous solution and ethyl acetate into the reaction solution in sequence for extraction twice, 2, adding 50mL of the saturated NaCl aqueous solution and 25mL of ethyl acetate for the first time for primary extraction, 3, collecting an organic layer after the primary extraction is finished, adding 25mL of ethyl acetate into the aqueous phase layer again for secondary extraction, drying the organic layer by anhydrous sodium sulfate after the extraction is finished, filtering, taking the filtrate, and evaporating to dryness at normal temperature under reduced pressure to obtain a crude compound. And (3) performing silica gel column chromatography on the crude compound, wherein the volume ratio of ethyl acetate to petroleum ether is 1: the solution 1 is a mobile phase, an eluent with the Rf value of 0.3 is collected by TLC tracking, the solvent is removed by rotary evaporation and reduced pressure at normal temperature after the collected eluent, and the pure compound shown as the formula 2p is obtained by drying, wherein the pure compound is 2.18mg, and the reaction yield is 5%.
Claims (8)
1. A preparation method of trifluoromethylated aniline compound shown as a formula (IIA) is characterized by comprising the following steps: taking a DMF (dimethyl formamide) and water mixed solvent with a volume ratio of 1: 1-4 as a reaction medium, adding an aniline compound shown in formula (IA), 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -ketone and a photocatalyst, reacting for 2-6H at room temperature under blue light, and after the reaction is completed, carrying out aftertreatment on the obtained reaction mixture to obtain a trifluoromethylated aniline compound shown in formula (IIA);
wherein R in the formula (IA) and the formula (IIA)2When it is methoxy, R1Is halogen; or R2When is H, R1Is C1-C3Alkyl, halogen, cyano, methoxy, acetyl, boroester, phenyl, -COOCH3、-COOC2H5or-COONHCH3；
The volume of the mixed solvent is 10mL/mmol based on the mass of the aniline compound shown in the formula (IA); the photocatalyst is tris (2,2' -bipyridyl) ruthenium dichloride, eosin Y, tris (2-phenylpyridine) iridium, fluorescein or rhodamine B; the mass ratio of the aniline compound shown in the formula (IA), the 1- (trifluoromethyl) -1, 2-phenyliodosyl-3 (1H) -ketone and the photocatalyst is 1: 1-3: 0.01-0.5.
2. The method for producing trifluoromethylated aniline compounds according to claim 1, wherein the trifluoromethylated aniline compound represented by the formula (IIA) is one of the following compounds:
3. the method for producing a trifluoromethylated aniline compound according to claim 1 or 2, wherein the photocatalyst is fluorescein.
4. The method for producing trifluoromethylated aniline compound according to claim 1, wherein the post-treatment is: adding saturated NaCl aqueous solution and ethyl acetate into the reaction mixture in sequence for extraction, collecting an organic layer after primary extraction, adding ethyl acetate into a water phase layer again for secondary extraction, combining the organic layers after the extraction is finished, drying and filtering the organic layers by anhydrous sodium sulfate, taking filtrate, and rotationally evaporating the solvent at normal temperature to obtain a crude product; and (3) performing silica gel column chromatography on the crude product, wherein the volume ratio is 1: and (3) taking a mixed solution of ethyl acetate and petroleum ether of 1-15 as an eluent, carrying out column chromatography separation, collecting a eluent containing a target product, removing the solvent under reduced pressure, and drying to obtain the trifluoromethylated aniline compound shown in the formula (IIA).
5. A preparation method of trifluoromethylated aniline compound shown as a formula (IIB) is characterized by comprising the following steps: taking a DMF (dimethyl formamide) and water mixed solvent with a volume ratio of 1: 1-4 as a reaction medium, adding an aniline compound shown in formula (IB), 1- (trifluoromethyl) -1, 2-phenyliodoyl-3 (1H) -ketone and a photocatalyst, reacting for 2-6H at a room temperature under blue light, and after the reaction is completed, carrying out aftertreatment on the obtained reaction mixture to obtain a trifluoromethylated aniline compound shown in formula (IIB);
wherein in the formulae (IB) and (IIB), R3Is C1-C3An alkyl group;
the volume of the mixed solution is 10mL/mmol based on the mass of the aniline compound shown in the formula (IB); the photocatalyst is tris (2,2' -bipyridyl) ruthenium dichloride, eosin Y, tris (2-phenylpyridine) iridium, fluorescein or rhodamine B; the mass ratio of the aniline compound shown in the formula (IB), the 1- (trifluoromethyl) -1, 2-phenyliodosyl-3 (1H) -ketone and the photocatalyst is 1: 1-3: 0.01-0.5.
6. The method for producing trifluoromethylated aniline compounds according to claim 1, wherein the trifluoromethylated aniline compound represented by the formula (IIB) is
7. The method for producing trifluoromethylated aniline compound according to claim 5 or 6, wherein the photocatalyst is fluorescein.
8. The method for producing trifluoromethylated aniline compound according to claim 1, wherein the post-treatment is: adding saturated NaCl aqueous solution and ethyl acetate into the reaction mixture in sequence for extraction, collecting an organic layer after primary extraction, adding ethyl acetate into a water phase layer again for extraction, combining the organic layers after extraction is finished, drying and filtering the organic layers through anhydrous sodium sulfate, taking filtrate, and rotationally evaporating the solvent at normal temperature to obtain a crude product; and (3) performing silica gel column chromatography on the crude product, wherein the volume ratio is 1: and (2) taking a mixed solution of ethyl acetate and petroleum ether of 1-15 as an eluent, carrying out column chromatography separation, collecting a eluent containing a target product, and removing the solvent under reduced pressure to obtain the trifluoromethylated aniline compound shown in the formula (IIA) or the formula (IIB).
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Application publication date: 20201211 |