CN113135869B - 一种制备α-芳基羰基化合物的方法及产品 - Google Patents
一种制备α-芳基羰基化合物的方法及产品 Download PDFInfo
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- 238000000034 method Methods 0.000 title claims abstract description 30
- -1 iodobenzene diacetate compound Chemical class 0.000 claims abstract description 39
- 238000006243 chemical reaction Methods 0.000 claims abstract description 24
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 16
- 150000002367 halogens Chemical class 0.000 claims abstract description 16
- 125000001424 substituent group Chemical group 0.000 claims abstract description 11
- 239000002841 Lewis acid Substances 0.000 claims abstract description 9
- 150000007517 lewis acids Chemical class 0.000 claims abstract description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 23
- 150000001875 compounds Chemical class 0.000 claims description 21
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 claims description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- 239000002585 base Substances 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 5
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 claims description 4
- XEFCWBLINXJUIV-UHFFFAOYSA-N acetic acid;iodobenzene Chemical class CC(O)=O.CC(O)=O.IC1=CC=CC=C1 XEFCWBLINXJUIV-UHFFFAOYSA-N 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 125000005936 piperidyl group Chemical group 0.000 claims description 3
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 claims description 3
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- LHJCZOXMCGQVDQ-UHFFFAOYSA-N tri(propan-2-yl)silyl trifluoromethanesulfonate Chemical compound CC(C)[Si](C(C)C)(C(C)C)OS(=O)(=O)C(F)(F)F LHJCZOXMCGQVDQ-UHFFFAOYSA-N 0.000 claims description 2
- STMPXDBGVJZCEX-UHFFFAOYSA-N triethylsilyl trifluoromethanesulfonate Chemical compound CC[Si](CC)(CC)OS(=O)(=O)C(F)(F)F STMPXDBGVJZCEX-UHFFFAOYSA-N 0.000 claims description 2
- 125000003504 2-oxazolinyl group Chemical class O1C(=NCC1)* 0.000 claims 1
- SNHMUERNLJLMHN-UHFFFAOYSA-N iodobenzene Chemical compound IC1=CC=CC=C1 SNHMUERNLJLMHN-UHFFFAOYSA-N 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 abstract description 8
- 125000000592 heterocycloalkyl group Chemical group 0.000 abstract description 8
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 abstract description 6
- 125000004453 alkoxycarbonyl group Chemical group 0.000 abstract description 5
- 125000004093 cyano group Chemical group *C#N 0.000 abstract description 5
- 125000003545 alkoxy group Chemical group 0.000 abstract description 4
- 125000003118 aryl group Chemical group 0.000 abstract description 4
- 125000004104 aryloxy group Chemical group 0.000 abstract description 4
- 125000000753 cycloalkyl group Chemical group 0.000 abstract description 4
- 125000001188 haloalkyl group Chemical group 0.000 abstract description 4
- 125000000547 substituted alkyl group Chemical group 0.000 abstract description 4
- 239000003513 alkali Substances 0.000 abstract description 3
- 238000000926 separation method Methods 0.000 abstract description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 48
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 20
- 238000005160 1H NMR spectroscopy Methods 0.000 description 14
- 239000007788 liquid Substances 0.000 description 11
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 10
- 235000019439 ethyl acetate Nutrition 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- ZBIKORITPGTTGI-UHFFFAOYSA-N [acetyloxy(phenyl)-$l^{3}-iodanyl] acetate Chemical compound CC(=O)OI(OC(C)=O)C1=CC=CC=C1 ZBIKORITPGTTGI-UHFFFAOYSA-N 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 239000003814 drug Substances 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 150000002918 oxazolines Chemical class 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 4
- 239000007832 Na2SO4 Substances 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 238000006462 rearrangement reaction Methods 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- QOLHWXNSCZGWHK-BWBORTOCSA-N (6r,7r)-1-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-4,7-dihydroxy-6-(11-phenoxyundecylcarbamoyloxy)-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid Chemical compound C([C@@H](C)[C@H](OC(C)=O)C(=C)CCC12[C@@H]([C@@H](OC(=O)NCCCCCCCCCCCOC=3C=CC=CC=3)C(O1)(C(O)=O)C(O)(C(O2)C(O)=O)C(O)=O)O)C1=CC=CC=C1 QOLHWXNSCZGWHK-BWBORTOCSA-N 0.000 description 3
- OEENXWLHBPUUFL-UHFFFAOYSA-N 2-pentyl-4,5-dihydro-1,3-oxazole Chemical compound CCCCCC1=NCCO1 OEENXWLHBPUUFL-UHFFFAOYSA-N 0.000 description 3
- 229940126559 Compound 4e Drugs 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 230000005012 migration Effects 0.000 description 3
- 238000013508 migration Methods 0.000 description 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 230000002194 synthesizing effect Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- KXVKWZFUSKQARU-UHFFFAOYSA-N CC(C)CCCC1=NCCO1 Chemical compound CC(C)CCCC1=NCCO1 KXVKWZFUSKQARU-UHFFFAOYSA-N 0.000 description 2
- YXXNEKREPCFWFS-UHFFFAOYSA-N N-(2-chloroethyl)hexanamide Chemical compound CCCCCC(=O)NCCCl YXXNEKREPCFWFS-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 229960004365 benzoic acid Drugs 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- VIMMECPCYZXUCI-MIMFYIINSA-N (4s,6r)-6-[(1e)-4,4-bis(4-fluorophenyl)-3-(1-methyltetrazol-5-yl)buta-1,3-dienyl]-4-hydroxyoxan-2-one Chemical compound CN1N=NN=C1C(\C=C\[C@@H]1OC(=O)C[C@@H](O)C1)=C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 VIMMECPCYZXUCI-MIMFYIINSA-N 0.000 description 1
- YXZFFTJAHVMMLF-UHFFFAOYSA-N 1-bromo-3-methylbutane Chemical compound CC(C)CCBr YXZFFTJAHVMMLF-UHFFFAOYSA-N 0.000 description 1
- GUXJXWKCUUWCLX-UHFFFAOYSA-N 2-methyl-2-oxazoline Chemical compound CC1=NCCO1 GUXJXWKCUUWCLX-UHFFFAOYSA-N 0.000 description 1
- SAFZQLDSMLNONX-UHFFFAOYSA-N 2-phenoxyethenylbenzene Chemical group C=1C=CC=CC=1OC=CC1=CC=CC=C1 SAFZQLDSMLNONX-UHFFFAOYSA-N 0.000 description 1
- WSNKEJIFARPOSQ-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-(1-benzothiophen-2-ylmethyl)benzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NCC2=CC3=C(S2)C=CC=C3)C=CC=1 WSNKEJIFARPOSQ-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- WRCUVAKWABKCNE-UHFFFAOYSA-N CC(C1=NCCO1)C(C=CC=C1)=C1I Chemical compound CC(C1=NCCO1)C(C=CC=C1)=C1I WRCUVAKWABKCNE-UHFFFAOYSA-N 0.000 description 1
- FILQAEDOGKFZNM-UHFFFAOYSA-N COCCCCCCCC1=NCCO1 Chemical compound COCCCCCCCC1=NCCO1 FILQAEDOGKFZNM-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- UPPGAVXYIVUREZ-UHFFFAOYSA-N O1C(=NCC1)C1=C(C=CC=C1)I Chemical compound O1C(=NCC1)C1=C(C=CC=C1)I UPPGAVXYIVUREZ-UHFFFAOYSA-N 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 125000005361 aryl sulfoxide group Chemical group 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 238000006757 chemical reactions by type Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 125000005520 diaryliodonium group Chemical group 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- YWGHUJQYGPDNKT-UHFFFAOYSA-N hexanoyl chloride Chemical compound CCCCCC(Cl)=O YWGHUJQYGPDNKT-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 230000001617 migratory effect Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- YHBXLSOKBAEPMQ-UHFFFAOYSA-N n,2-dichloroethanamine Chemical compound ClCCNCl YHBXLSOKBAEPMQ-UHFFFAOYSA-N 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 125000003011 styrenyl group Chemical group [H]\C(*)=C(/[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229930192474 thiophene Chemical group 0.000 description 1
- 125000006248 tosyl amino group Chemical group [H]N(*)S(=O)(=O)C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/04—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/52—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen
- C07C57/58—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/04—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D263/06—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by oxygen atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明公开了一种制备α‑芳基羰基化合物的方法,包括:R1取代二醋酸碘苯化合物经过路易斯酸活化,然后与R2取代噁唑啉化合物在碱存在下反应得到所述α‑芳基羰基化合物;所述R1选自H、一个或多个烷基、一个或多个卤代烷基、烷氧羰基、卤素或者上述原子组合形成的多取代;R2选自H、烷基、取代烷基,其中取代基选自环烷基、卤素、烷氧基、杂环烷基、取代杂环烷基、芳基、氰基、芳氧基、羰基。该方法反应条件温和,产物易分离、操作简单。
Description
技术领域
本发明属于有机化学合成领域,特别涉及一种制备α-芳基羰基化合物的新方法及产品。
背景技术
由于α-芳基羰基化合物的重要性,被广泛的研究。目前是许多药物活性分子合成的重要中间体。α-芳基羰基化合物主要用于医药领域中新药的开发.
含有α-芳基羰基片段的化合物在医药领域中具有重要的药物活性和生理性。(J.Org.Chem.2001,66:3653;J.Med.Chem.1986,29:523;J.Am.Chem.Soc.1985,107:435;J.Am.Chem.Soc.1999,121:2147.)。
到目前为止,一些α-芳基羰基化合物的合成方法已经被相继报道。
环酮类化合物在金属试剂的作用下可以与二芳基碘鎓盐反应制备α-芳基羰基化合物(Tetrahedron Lett.1997,38:5061;Organometallics 1997,16:3241.)。可是该类反应需要当量的金属催化剂,而且使用了强碱,官能团兼容性差。
羰基化合物和卤代芳烃在金属钯,镍或铜的催化下也可用于α-芳基羰基化合物的合成(Angew.Chem.Int.Ed.1997,36:1740;J.Am.Chem.Soc.1997,119:1110;J.Org.Chem.2007,72:5069;J.Chem.Soc.1929,1870.)。可是该类方法选择性差,底物范围窄,官能团兼容性差。
通过芳基亚砜和1,3-二羰基化合物或者腈类化合物的[3,3]迁移重排反应也可用于α-芳基羰基化合物的合成(J.Am.Chem.Soc.2011,133:8510;J.Am.Chem.Soc.2017,139:4211)。但是该类方法底物特殊,而且反应对水分很敏感。
发明内容
为了克服现有技术中存在的缺陷,本发明提供了一种制备α-芳基羰基化合物的新方法,具有反应条件温和、产物易分离、操作简单等优点。
一种制备α-芳基羰基化合物的方法,包括:R1取代二醋酸碘苯化合物经过路易斯酸活化,然后与R2取代噁唑啉化合物在碱存在下反应得到所述α-芳基羰基化合物;
所述R1选自H、一个或多个烷基、一个或多个卤代烷基、烷氧羰基、卤素或者上述原子组合形成的多取代;R2选自H、烷基、取代烷基,其中取代基选自环烷基、卤素、烷氧基、杂环烷基、取代杂环烷基、芳基、氰基、芳氧基、羰基。
本发明提供了制备α-芳基羰基化合物的新方法,其采用在有机溶剂存在下通过二醋酸碘苯和噁唑啉的[3,3]迁移重排反应合成α-芳基羰基化合物。
作为优选,所述R1选自H、一个或多个C1~C3烷基、一个或多个卤代C1~C3烷基、C1~C3烷氧羰基、卤素或者上述原子组合形成的多取代;R2选自H、C1~C10烷基、取代C1~C10烷基,其中取代基选自环己基、卤素、C1~C3烷氧基、哌啶基、取代哌啶基、苯基、卤素取代苯基、氰基、苯氧基、卤素取代苯氧基、苯乙烯取代羰基、噻吩取代羰基。
作为进一步优选,所述R1选自H、甲基、多个甲基多取代、卤代甲基、多个卤代甲基多取代、甲氧羰基、卤素或者卤素与一个或多个甲基组成的多取代;多取代时,可以是间位取代、对位取代等。
作为进一步优选,所述R2选自H、正丁基、甲基、异丙基取代乙基(1位或2位取代)、异丁基、异丙基、环己基甲基、氯代丙基(1位、2位、3位取代)、溴代正己基(可以任意的为1~6位取代)、I代11烷基、6-(对甲苯磺酰基氧基)己基、甲氧基取代正己基(可以任意的为1~6位取代)、N位取代的哌啶-6-基(比如N-对甲苯磺酰基取代)乙基、2-对溴苯基乙基、氰基取代的戊基、4-对氯甲基氧基正丁基、1-庚烯-7-基、2-甲氧羰基乙基等。
作为一种方案,所述α-芳基羰基化合物经过进一步水解得到对应的羧酸化合物:
该化合物可以用于合成多种现有或者新的化合物。R1、R2取代情况如上述内容所述。
所述水解可以在硫酸等无机酸溶液中进行,反应溶剂可以采用1,4-二氧六环、甲苯等,反应温度可以为80~120℃。
利用上述羧酸化合物可以进一步还原得到对应的醇化合物,也可以与醇化合物或者氨化合物反应得到对应的酯化合物和酰胺化合物等。羧酸化合物上碘取代位置,可以与烯烃化合物(比如苯乙烯)或者炔烃化合物(苯乙炔)反应,得到对应的苯代烯烃化合物(苯乙烯取代苯羧酸化合物)或苯代炔烃化合物(苯乙炔取代苯羧酸化合物);或者与苯基硼酸反应,联苯基取代的羧酸化合物。或者以上反应类型的组合制备现有的药物或药物中间,或者制备新的药物或者药物中间体等。
作为优选,所述的路易斯酸为三氟甲磺酸三甲基硅酯、三氟甲磺酸三乙基硅酯、三氟甲磺酸三异丙基硅酯中的一种或多种。
作为优选,反应温度为:-50℃~30℃;进一步优选为:-40℃~25℃。反应在有机溶剂中进行,所述有机溶剂为二氯甲烷、乙腈中的一种或者混合物。
作为优选,所用到的碱为2-甲基吡啶、三乙烯二胺、三乙胺、二异丙基乙基胺和1,8-二氮杂二环十一碳-7-烯中的一种或多种。
作为优选,所述R1取代二醋酸碘苯化合物与R2取代噁唑啉化合物的摩尔比为1:(1~3);所述R1取代二醋酸碘苯化合物与路易斯酸的摩尔比为1:(1~3);所述R1取代二醋酸碘苯化合物与碱的摩尔比为1:(1~3)。也就是说,所述方法中各物质的当量为:R1取代二醋酸碘苯1.0equiv,R2取代噁唑啉1.0至3.0equiv,路易斯酸1.0至3.0equiv,碱1.0至3.0equiv。
本发明方法的具体工艺包括以下步骤:-40℃下在100mL反应瓶内称取R1取代二醋酸碘苯,将溶剂加入到其中,然后加入路易斯酸,搅拌均匀,适当时间后加入R2取代噁唑啉,适当时间后加入碱,用薄层色谱法跟踪反应进程,展开剂为石油醚/乙酸乙酯的体积比为(3/1)。反应结束后,将反应物料减压浓缩,柱层析法分离,得到α-芳基羰基化合物。
一种化合物,结构如下式所示:
所述R1选自H、一个或多个烷基、一个或多个卤代烷基、烷氧羰基、卤素或者上述原子组合形成的多取代;R2选自H、烷基、取代烷基,其中取代基选自环烷基、卤素、烷氧基、杂环烷基、取代杂环烷基、芳基、氰基、芳氧基、羰基。
常见的结构如下:
一种化合物,结构如下式所示:
所述R1选自H、一个或多个烷基、一个或多个卤代烷基、烷氧羰基、卤素或者上述原子组合形成的多取代;R2选自烷基、取代烷基,其中取代基选自环烷基、卤素、烷氧基、杂环烷基、取代杂环烷基、芳基、氰基、芳氧基、羰基。
本发明中R1取代二醋酸碘苯化合物与R2取代噁唑啉化合物可以直接市购,也可以自行制备得到。
与现有方法相比,本方法通过R1取代二醋酸碘苯和R2取代噁唑啉的[3,3]迁移重排反应合成α-芳基羰基化合物,其优势在于:
本方法反应条件温和、选择性好,产物易分离、操作简单;
本方法所用原料价廉易得,避免了传统方法中用到的很难制备和购买的催化剂,反应条件苛刻;
利用二醋酸碘苯和噁唑啉的[3,3]迁移重排反应,能够制备化学稳定的α-芳基羰基化合物,为这一类化合物的合成提供了新的反应策略。
具体实施方式
以下介绍本发明提供的制备α-芳基羰基化合物的新方法的具体实施实例,提供了多个具体实施实例。应当指出的是,本发明的实施不局限于以下实施实例。
实施例中R1取代二醋酸碘苯原料采用市购产品,R2取代噁唑啉部分来源于市购,其中部分化合物的制备方法为:
2-戊基-4,5-二氢噁唑(4a):
在0℃下,向2-氯乙基氨盐酸盐(10.21g,88mmol)和Et3N(28mL,200mmol)的DCM(267mL)溶液中滴加己酰氯(11.2mL,80mmol)。体系液升温至室温,搅拌3h。用水淬灭体系液,DCM萃取,Na2SO4干燥,浓缩.浓缩液重结晶(DCM and PE)得到N-(2-氯乙基)己酰胺白色固体9.67g,产率为68%。(Rf=0.48,eluent:PE/EtOAc=1/1)。
向N-(2-氯乙基)己酰胺(9.67g,54mmol)的MeOH(360mL)溶液中加入NaOH(3.02g,76mmol)。回流过夜,浓缩,饱和NaHCO3水溶液稀释,DCM萃取。合并有机层,Na2SO4干燥,浓缩。残留物利用柱层析纯化得到浅黄色油状物化合物4a:2-戊基-4,5-二氢噁唑,5.95g,收率78%。(Rf=0.20,eluent:PE/EtOAc=3/1)。1H NMR(600MHz,CDCl3):δ4.18(t,J=9.5Hz,2H),3.78(t,J=9.5Hz,2H),2.22(t,J=7.7Hz,2H),1.66–1.54(m,2H),1.35–1.24(m,4H),0.86(t,J=6.6Hz,3H)。
2-(4-甲基戊基)-4,5-二氢噁唑(4e):
在-78℃条件下,向2-甲基-4,5-二氢噁唑(1.70g,20mmol)的THF(67mL)溶液中滴加n-BuLi(2.5M,8.8mL)。搅拌3h,-78℃条件下滴加1-溴-3-甲基丁烷(3.02g,20mmol)的THF(14.0mL)溶液。继续搅拌1h,体系液升温至室温,搅拌过夜。加入水,利用DCM萃取,合并有机层,Na2SO4干燥,浓缩,残留物经过柱层析纯化得到化合物4e,2.30g,收率74%。(Rf=0.25,eluent:PE/EtOAc=2/1)。1H NMR(600MHz,CDCl3):δ4.21(t,J=9.5Hz,2H),3.81(t,J=9.5Hz,2H),2.26–2.21(m,2H),1.65–1.58(m,2H),1.58–1.51(m,1H),1.24–1.18(m,2H),0.87(d,J=6.6Hz,6H)。
2-(2-(1-Ts-哌啶-4-基)乙基)-4,5-二氢噁唑(4l):
按照化合物4e的制备方法,利用15mmol对应的溴代烷基得到白色固体化合物(4l)m.p.134–136℃,2.37g,产率47%。(Rf=0.33,eluent:PE/EtOAc=1/2).1H NMR(600MHz,CDCl3):δ7.60(d,J=8.2Hz,2H),7.29(d,J=8.0Hz,2H),4.16(t,J=9.5Hz,2H),3.78–3.68(m,4H),2.40(s,3H),2.24–2.15(m,4H),1.75–1.67(m,2H),1.57–1.49(m,2H),1.31–1.15(m,3H)。
2-(7-甲氧庚基)-4,5-二氢噁唑(4m):
按照化合物4e的制备方法,利用8mmol对应的溴代烷基得到黄色油状物化合物4m:924.8mg,收率58%.(Rf=0.21,eluent:PE/EtOAc=1/1)。1H NMR(600MHz,CDCl3):δ4.20(t,J=9.5Hz,2H),3.80(t,J=9.5Hz,2H),3.34(t,J=6.6Hz,2H),3.31(s,3H),2.25(t,J=7.7Hz,2H),1.65–1.58(m,2H),1.58–1.51(m,2H),1.38–1.28(m,6H)。
其他底物可以采用上述相似的方法制备得到,或者市购。
制备方法:
在100毫升的反应瓶内进行抽真空,抽换氮气三次,在氮气保护下加入R1取代二醋酸碘苯(1.0mmol,1.0eq)和无水的DCM(10mL,0.1M)并置于-40℃,然后加入三氟甲磺酸三甲基硅酯(2.0mmol,2.0eq.),反应10分钟后加入R2取代噁唑啉(2.0mmol,2.0eq.),再过10分钟后,加入2-甲基吡啶(2.0mmol,2.0eq.)。24小时后用薄层色谱法跟踪反应进程,展开剂为石油醚/乙酸乙酯的体积比为3/1,监测到反应结束,饱和碳酸氢钠处理,DCM萃取,合并有机相并用Na2SO4干燥,将有机相通过减压浓缩,柱层析法分离得到产物。
实施例1
R1取H,R2取正丁基,按照上述方法得到212.8mg黄色液体化合物1,收率是62%。
1H NMR(600MHz,CDCl3):δ7.83(d,J=7.9Hz,1H),7.38–7.34(m,1H),7.30(t,J=7.5Hz,1H),6.95–6.88(m,1H),4.26–4.19(m,1H),4.19–4.13(m,1H),4.01(t,J=7.5Hz,1H),3.85(t,J=9.5Hz,2H),2.07–1.97(m,1H),1.83–1.74(m,1H),1.39–1.29(m,3H),1.25–1.18(m,1H),0.86(t,J=7.2Hz,3H).
13C NMR(151MHz,CDCl3):δ169.1,143.2,139.7,128.8,128.7,127.9,101.8,67.4,54.4,48.9,34.0,29.6,22.7,14.0.
IR(neat):2954,2929,2871,1659,1583,1561,1460,1435,1171,1108,732.
HRMS(ESI-TOF):calculated for[C14H19INO(M+H+)]:344.0506,found:344.0508.
实施例2
R1取H,R2取异戊基,通过同样的方法可以得到225.0mg黄色液体化合物2,收率是63%。
1H NMR(600MHz,CDCl3):δ7.86–7.82(m,1H),7.39–7.35(m,1H),7.33–7.29(m,1H),6.95–6.90(m,1H),4.26–4.14(m,2H),3.99(t,J=7.5Hz,1H),3.90–3.80(m,2H),2.06–1.98(m,1H),1.84–1.76(m,1H),1.59–1.51(m,1H),1.32–1.23(m,1H),1.14–1.06(m,1H),0.88–0.83(m,6H).
13C NMR(151MHz,CDCl3):δ169.2,143.3,139.8,128.8,128.7,128.0,101.9,67.5,54.5,49.2,36.5,32.2,28.1,22.7,22.6.
IR(neat):2952,2901,2869,1660,1465,1435,1383,1365,1171,732.
HRMS(ESI-TOF):calculated for[C15H21INO(M+H+)]:358.0662,found:358.0662.
实施例3
R1取H,R2取环己基甲基,通过同样的方法可以得到210.8mg白色固体化合物3,收率是55%。1H NMR(600MHz,CDCl3):δ7.88–7.80(m,1H),7.41–7.37(m,1H),7.33–7.28(m,1H),6.96–6.89(m,1H),4.26–4.20(m,1H),4.19–4.12(m,2H),3.89–3.79(m,2H),1.96–1.89(m,1H),1.84–1.74(m,2H),1.70–1.58(m,4H),1.28–1.12(m,4H),1.00–0.89(m,2H).
13C NMR(151MHz,CDCl3):δ169.3,143.6,139.9,128.8,128.7,128.1,101.6,67.4,54.5,46.3,42.0,35.3,33.7,33.4,26.6,26.3,26.2.
IR(neat):2921,2886,2849,2836,1665,1464,1446,1180,765.
HRMS(ESI-TOF):calculated for[C17H23INO(M+H+)]:384.0819,found:384.0813.
实施例4
R1取H,R2取3-氯丙基,通过同样的方法可以得到196.3mg黄色液体化合物4,收率是60%。1H NMR(600MHz,CDCl3):δ7.85–7.80(m,1H),7.35–7.32(m,1H),7.32–7.28(m,1H),6.96–6.87(m,1H),4.25–4.19(m,1H),4.19–4.12(m,1H),4.03(t,J=7.3Hz,1H),3.84(t,J=9.7Hz,2H),3.51(t,J=6.5Hz,2H),2.20–2.12(m,1H),1.98–1.84(m,2H),1.76–1.68(m,1H).
13C NMR(151MHz,CDCl3):δ168.5,142.5,139.8,129.0,128.8,127.8,101.6,67.5,54.4,48.2,44.7,31.5,30.4.
IR(neat):2954,2879,1659,1583,1562,1464,1434,1010,750,728.
HRMS(ESI-TOF):calculated for[C13H16ClINO(M+H+)]:363.9960,found:363.9958.
实施例5
R1取H,R2取6-甲氧基己基,通过同样的方法可以得到240.8mg黄色液体化合物5,收率是60%。
1H NMR(600MHz,CDCl3):δ7.85–7.81(m,1H),7.37–7.33(m,1H),7.32–7.28(m,1H),6.94–6.90(m,1H),4.25–4.19(m,1H),4.19–4.13(m,1H),4.01(t,J=7.5Hz,1H),3.88–3.81(m,2H),3.34–3.31(m,2H),3.30(s,3H),2.06–1.98(m,1H),1.82–1.74(m,1H),1.55–1.50(m,2H),1.39–1.25(m,6H).
13C NMR(151MHz,CDCl3):δ169.1,143.2,139.8,128.8,128.7,128.0,101.8,73.0,67.4,58.6,54.5,48.9,34.2,29.7,29.4,27.4,26.0.
IR(neat):2928,2855,1660,1463,1435,1115,1010,982,729.
HRMS(ESI-TOF):calculated for[C17H25INO2(M+H+)]:402.0924,found:402.0912。
实施例6
R1取H,R2取N-Ts哌啶-1-基-甲基,通过同样的方法可以得到323.0mg黄色液体化合物6,收率是60%。1H NMR(600MHz,CDCl3):δ7.60–7.72(m,1H),7.58–7.52(m,2H),7.29–7.26(m,1H),7.26–7.21(m,3H),6.88–6.82(m,1H),4.16–4.10(m,1H),4.09–4.00(m,2H),3.75(t,J=9.5Hz,2H),3.68(d,J=11.5Hz,2H),2.35(s,3H),2.17–2.09(m,2H),1.94–1.87(m,1H),1.81(d,J=12.7Hz,1H),1.73(d,J=12.8Hz,1H),1.64–1.58(m,1H),1.38–1.23(m,2H),1.21–1.16(m,1H).
13C NMR(151MHz,CDCl3):δ168.6,143.4,142.7,139.8,133.1,129.6,129.0,128.8,127.8,127.7,101.4,67.4,54.3,46.3,46.2,46.0,40.4,32.7,31.7,31.4,21.5.
IR(neat):2917,2843,1658,1596,1435,1194,1144,1094,814.
HRMS(ESI-TOF):calculated for[C23H28IN2O3S(M+H+)]:539.0860,found:539.0830.
实施例7
R1取甲基(I取代的对位),R2取正丁基,通过同样的方法可以得到235.8mg黄色液体化合物7,收率是66%。
1H NMR(600MHz,CDCl3):δ7.69(d,J=8.1Hz,1H),7.17–7.14(m,1H),6.78–6.73(m,1H),4.27–4.14(m,2H),3.97(t,J=7.5Hz,1H),3.90–3.82(m,2H),2.28(s,3H),2.07–1.96(m,1H),1.82–1.73(m,1H),1.39–1.30(m,3H),1.25–1.19(m,1H),0.87(t,J=7.2Hz,3H).
13C NMR(151MHz,CDCl3):δ169.4,142.9,139.4,138.7,130.0,128.6,97.8,67.5,54.4,48.7,34.1,29.6,22.8,21.2,14.1.
IR(neat):2954,2928,2871,1159,1466,1171,1008,984,806,731.
HRMS(ESI-TOF):calculated for[C15H21INO(M+H+)]:358.0662,found:358.0656.
实施例8
R1取Cl(I取代的对位),R2取正丁基,通过同样的方法可以得到151.1mg黄色液体化合物8,收率是40%。
1H NMR(400MHz,CDCl3):δ7.73(d,J=8.4Hz,1H),7.35(d,J=2.5Hz,1H),6.94–6.89(m,1H),4.27–4.15(m,2H),3.96(t,J=7.5Hz,1H),3.86(t,J=9.6Hz,2H),2.05–1.96(m,1H),1.78–1.71(m,1H),1.37–1.28(m,3H),1.25–1.19(m,1H),0.87(t,J=7.2Hz,3H).
13C NMR(101MHz,CDCl3):δ168.4,145.2,140.6,135.0,129.0,128.1,98.7,67.5,54.5,48.9,34.0,29.5,22.6,14.0.
IR(neat):2953,2927,2870,1656,1575,1478,1455,1193,1105,732.
HRMS(ESI-TOF):calculated for[C14H18ClINO(M+H+)]:378.0116,found:378.0104.
实施例9
R1取H,R2取甲基,通过同样的方法可以得到225.8mg黄色液体化合物9,2-(1-(2-碘苯基)乙基)-4,5-二氢噁唑,75%yield.(Rf=0.20,eluent:PE/EtOAc=3/1)。
1H NMR(600MHz,CDCl3):δ7.83(d,J=7.9Hz,1H),7.30(d,J=4.0Hz,2H),6.96–6.88(m,1H),4.28–4.15(m,2H),4.13–4.04(m,1H),3.92–3.81(m,2H),1.48(d,J=7.1Hz,3H).
13C NMR(151MHz,CDCl3):δ169.8,144.3,139.8,128.80,128.79,127.5,100.8,67.7,54.5,43.7,19.2.
IR(neat):2975,2932,2901,2878,1659,1584,1466,1433,1181,1118,747.
HRMS(ESI-TOF):calculated for[C11H13INO(M+H+)]:302.0036,found:302.0030。
实施例10
R1取H,R2取H,通过同样的方法可以得到89mg黄色液体化合物10:2-(2-碘苯基)-4,5-二氢噁唑,31%yield.(Rf=0.33,eluent:PE/EtOAc=1/1)。
1H NMR(600MHz,CDCl3):δ7.86–7.81(m,1H),7.36–7.28(m,2H),6.97–6.92(m,1H),4.26(t,J=9.5Hz,2H),3.84(t,J=9.5Hz,2H),3.75(s,2H).
13C NMR(151MHz,CDCl3):δ166.0,139.7,138.6,130.2,128.9,128.5,100.9,67.8,54.7,39.8.
IR(neat):2902,2878,1662,1585,1563,1464,1206,1107,733.
HRMS(ESI-TOF):calculated for[C10H11INO(M+H+)]:287.9880,found:287.9879。
羧酸制备:
将化合物1~10按照如下方法即可得到对应的羧酸化合物:
向25mL反应管中加入化合物I(1.0mmol),4M的H2SO4(2.0mL)和1,4-二氧六环(2.0mL),然后在100℃下反应15h。反应结束后冷却至室温,并向其中加入2M的NaOH至碱性,然后减压浓缩。剩余物用1M的HCl酸化并用二氯甲烷萃取,有机相用无水Na2SO4干燥,减压浓缩后得到产物,产物不需要进一步纯化。
Claims (3)
1.一种制备α-芳基羰基化合物的方法,其特征在于,包括:R1取代二醋酸碘苯化合物经过路易斯酸活化,然后与R2取代噁唑啉化合物在碱存在下反应得到所述α-芳基羰基化合物;
所述R1选自H、一个或多个C1~C3烷基、一个或多个卤代C1~C3烷基、卤素或者上述取代基组合形成的多取代;
R2选自H、C1~C10烷基、取代C1~C10烷基,其中取代基选自环己基、卤素、C1~C3烷氧基、哌啶基;
所述的路易斯酸为三氟甲磺酸三甲基硅酯、三氟甲磺酸三乙基硅酯、三氟甲磺酸三异丙基硅酯中的一种或多种;
反应温度为:-50℃~30℃;反应在有机溶剂中进行,所述有机溶剂为二氯甲烷、乙腈中的一种或者混合物;
所用到的碱为2-甲基吡啶、三乙烯二胺、三乙胺、二异丙基乙基胺和1,8-二氮杂二环十一碳-7-烯中的一种或多种。
3.根据权利要求1所述的制备α-芳基羰基化合物的方法,其特征在于,所述R1取代二醋酸碘苯化合物与R2取代噁唑啉化合物的摩尔比为1:(1~3);所述R1取代二醋酸碘苯化合物与路易斯酸的摩尔比为1:(1~3);所述R1取代二醋酸碘苯化合物与碱的摩尔比为1:(1~3)。
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