CN116162027A - 一种铁催化羰基化三组分偶联反应合成ɑ,β-不饱和酮的方法 - Google Patents
一种铁催化羰基化三组分偶联反应合成ɑ,β-不饱和酮的方法 Download PDFInfo
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- CN116162027A CN116162027A CN202310191950.6A CN202310191950A CN116162027A CN 116162027 A CN116162027 A CN 116162027A CN 202310191950 A CN202310191950 A CN 202310191950A CN 116162027 A CN116162027 A CN 116162027A
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- 150000002576 ketones Chemical class 0.000 title claims abstract description 39
- 238000000034 method Methods 0.000 title claims abstract description 30
- 238000005859 coupling reaction Methods 0.000 title claims abstract description 27
- 230000006315 carbonylation Effects 0.000 title claims abstract description 24
- 238000005810 carbonylation reaction Methods 0.000 title claims abstract description 24
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 23
- 238000006243 chemical reaction Methods 0.000 claims abstract description 92
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims abstract description 47
- 229910002091 carbon monoxide Inorganic materials 0.000 claims abstract description 47
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims abstract description 46
- 229910052742 iron Inorganic materials 0.000 claims abstract description 24
- -1 alkenyl boric acid Chemical compound 0.000 claims abstract description 20
- 239000003054 catalyst Substances 0.000 claims abstract description 16
- 150000001502 aryl halides Chemical class 0.000 claims abstract description 12
- 239000004327 boric acid Substances 0.000 claims abstract description 10
- 239000000126 substance Substances 0.000 claims abstract description 9
- 239000002904 solvent Substances 0.000 claims description 44
- 125000001424 substituent group Chemical group 0.000 claims description 26
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- 229920001223 polyethylene glycol Polymers 0.000 claims description 16
- 239000002202 Polyethylene glycol Substances 0.000 claims description 14
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 claims description 14
- 229960002089 ferrous chloride Drugs 0.000 claims description 14
- NMCUIPGRVMDVDB-UHFFFAOYSA-L iron dichloride Chemical compound Cl[Fe]Cl NMCUIPGRVMDVDB-UHFFFAOYSA-L 0.000 claims description 14
- 125000001624 naphthyl group Chemical group 0.000 claims description 14
- 125000005561 phenanthryl group Chemical group 0.000 claims description 14
- 125000001725 pyrenyl group Chemical group 0.000 claims description 14
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 claims description 10
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 10
- 235000017550 sodium carbonate Nutrition 0.000 claims description 10
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- 125000001931 aliphatic group Chemical group 0.000 claims description 9
- 150000002367 halogens Chemical group 0.000 claims description 9
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 8
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 6
- 125000001072 heteroaryl group Chemical group 0.000 claims description 6
- VCJMYUPGQJHHFU-UHFFFAOYSA-N iron(3+);trinitrate Chemical compound [Fe+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O VCJMYUPGQJHHFU-UHFFFAOYSA-N 0.000 claims description 6
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 125000004185 ester group Chemical group 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 claims description 4
- 235000019797 dipotassium phosphate Nutrition 0.000 claims description 4
- 229910000396 dipotassium phosphate Inorganic materials 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- BQZGVMWPHXIKEQ-UHFFFAOYSA-L iron(ii) iodide Chemical compound [Fe+2].[I-].[I-] BQZGVMWPHXIKEQ-UHFFFAOYSA-L 0.000 claims description 4
- 235000011056 potassium acetate Nutrition 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- 235000011181 potassium carbonates Nutrition 0.000 claims description 4
- 239000011698 potassium fluoride Substances 0.000 claims description 4
- 235000003270 potassium fluoride Nutrition 0.000 claims description 4
- SJRDNQOIQZOVQD-UHFFFAOYSA-M sodium;2,2-dimethylpropanoate Chemical compound [Na+].CC(C)(C)C([O-])=O SJRDNQOIQZOVQD-UHFFFAOYSA-M 0.000 claims description 4
- QVHJQCGUWFKTSE-YFKPBYRVSA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical group OC(=O)[C@H](C)NC(=O)OC(C)(C)C QVHJQCGUWFKTSE-YFKPBYRVSA-N 0.000 claims description 3
- LFKXWKGYHQXRQA-FDGPNNRMSA-N (z)-4-hydroxypent-3-en-2-one;iron Chemical compound [Fe].C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O LFKXWKGYHQXRQA-FDGPNNRMSA-N 0.000 claims description 3
- CDVAIHNNWWJFJW-UHFFFAOYSA-N 3,5-diethoxycarbonyl-1,4-dihydrocollidine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OCC)C1C CDVAIHNNWWJFJW-UHFFFAOYSA-N 0.000 claims description 3
- 229910021575 Iron(II) bromide Inorganic materials 0.000 claims description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 3
- MCDLETWIOVSGJT-UHFFFAOYSA-N acetic acid;iron Chemical compound [Fe].CC(O)=O.CC(O)=O MCDLETWIOVSGJT-UHFFFAOYSA-N 0.000 claims description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 3
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 claims description 3
- 239000000920 calcium hydroxide Substances 0.000 claims description 3
- 229910001861 calcium hydroxide Inorganic materials 0.000 claims description 3
- 235000011116 calcium hydroxide Nutrition 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 229910000397 disodium phosphate Inorganic materials 0.000 claims description 3
- 235000019800 disodium phosphate Nutrition 0.000 claims description 3
- VEPSWGHMGZQCIN-UHFFFAOYSA-H ferric oxalate Chemical compound [Fe+3].[Fe+3].[O-]C(=O)C([O-])=O.[O-]C(=O)C([O-])=O.[O-]C(=O)C([O-])=O VEPSWGHMGZQCIN-UHFFFAOYSA-H 0.000 claims description 3
- 229940046149 ferrous bromide Drugs 0.000 claims description 3
- 229940076136 ferrous iodide Drugs 0.000 claims description 3
- 229940062993 ferrous oxalate Drugs 0.000 claims description 3
- 239000011790 ferrous sulphate Substances 0.000 claims description 3
- 235000003891 ferrous sulphate Nutrition 0.000 claims description 3
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 3
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 claims description 3
- OWZIYWAUNZMLRT-UHFFFAOYSA-L iron(2+);oxalate Chemical compound [Fe+2].[O-]C(=O)C([O-])=O OWZIYWAUNZMLRT-UHFFFAOYSA-L 0.000 claims description 3
- RUTXIHLAWFEWGM-UHFFFAOYSA-H iron(3+) sulfate Chemical compound [Fe+3].[Fe+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O RUTXIHLAWFEWGM-UHFFFAOYSA-H 0.000 claims description 3
- 229910000359 iron(II) sulfate Inorganic materials 0.000 claims description 3
- 229910000360 iron(III) sulfate Inorganic materials 0.000 claims description 3
- GYCHYNMREWYSKH-UHFFFAOYSA-L iron(ii) bromide Chemical compound [Fe+2].[Br-].[Br-] GYCHYNMREWYSKH-UHFFFAOYSA-L 0.000 claims description 3
- FZGIHSNZYGFUGM-UHFFFAOYSA-L iron(ii) fluoride Chemical compound [F-].[F-].[Fe+2] FZGIHSNZYGFUGM-UHFFFAOYSA-L 0.000 claims description 3
- SHXXPRJOPFJRHA-UHFFFAOYSA-K iron(iii) fluoride Chemical compound F[Fe](F)F SHXXPRJOPFJRHA-UHFFFAOYSA-K 0.000 claims description 3
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 claims description 3
- 229910052808 lithium carbonate Inorganic materials 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 239000011736 potassium bicarbonate Substances 0.000 claims description 3
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 3
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 3
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 3
- 235000011118 potassium hydroxide Nutrition 0.000 claims description 3
- 239000001632 sodium acetate Substances 0.000 claims description 3
- 235000017281 sodium acetate Nutrition 0.000 claims description 3
- 235000011121 sodium hydroxide Nutrition 0.000 claims description 3
- 239000001488 sodium phosphate Substances 0.000 claims description 3
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 3
- 235000011008 sodium phosphates Nutrition 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- FEONEKOZSGPOFN-UHFFFAOYSA-K tribromoiron Chemical compound Br[Fe](Br)Br FEONEKOZSGPOFN-UHFFFAOYSA-K 0.000 claims description 3
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 3
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 229910052740 iodine Chemical group 0.000 claims description 2
- 239000011630 iodine Chemical group 0.000 claims description 2
- OSHOQERNFGVVRH-UHFFFAOYSA-K iron(3+);trifluoromethanesulfonate Chemical compound [Fe+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F OSHOQERNFGVVRH-UHFFFAOYSA-K 0.000 claims description 2
- AIUIJBDEQKTMHT-UHFFFAOYSA-N perchloric acid;hydrate Chemical compound O.OCl(=O)(=O)=O AIUIJBDEQKTMHT-UHFFFAOYSA-N 0.000 claims description 2
- VTLYFUHAOXGGBS-UHFFFAOYSA-N Fe3+ Chemical compound [Fe+3] VTLYFUHAOXGGBS-UHFFFAOYSA-N 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 claims 1
- 239000000758 substrate Substances 0.000 abstract description 11
- 239000003513 alkali Substances 0.000 abstract description 9
- 230000007613 environmental effect Effects 0.000 abstract description 7
- 230000003197 catalytic effect Effects 0.000 abstract description 6
- 238000006555 catalytic reaction Methods 0.000 abstract description 6
- 125000000524 functional group Chemical group 0.000 abstract description 5
- 230000000694 effects Effects 0.000 abstract description 4
- 239000003446 ligand Substances 0.000 abstract description 4
- 239000012429 reaction media Substances 0.000 abstract description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 282
- 239000000047 product Substances 0.000 description 50
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 36
- 238000004587 chromatography analysis Methods 0.000 description 36
- 238000001704 evaporation Methods 0.000 description 36
- 230000008020 evaporation Effects 0.000 description 36
- 239000012074 organic phase Substances 0.000 description 36
- 239000003208 petroleum Substances 0.000 description 36
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 36
- 239000011541 reaction mixture Substances 0.000 description 36
- 230000002829 reductive effect Effects 0.000 description 36
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 36
- 150000001875 compounds Chemical class 0.000 description 9
- 230000000052 comparative effect Effects 0.000 description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 4
- 239000002253 acid Substances 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 229910000510 noble metal Inorganic materials 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- CSCPPACGZOOCGX-MICDWDOJSA-N 1-deuteriopropan-2-one Chemical compound [2H]CC(C)=O CSCPPACGZOOCGX-MICDWDOJSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 229920000604 Polyethylene Glycol 200 Polymers 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- NTAMHDOMEKTZDO-UHFFFAOYSA-N [Fe].C1(=CC=CC=C1)CC(C(=O)C1=CC=CC=C1)=O Chemical compound [Fe].C1(=CC=CC=C1)CC(C(=O)C1=CC=CC=C1)=O NTAMHDOMEKTZDO-UHFFFAOYSA-N 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000000460 chlorine Chemical group 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 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 description 2
- 239000012847 fine chemical Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 229940113115 polyethylene glycol 200 Drugs 0.000 description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 description 2
- 235000011009 potassium phosphates Nutrition 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 1
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 1
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- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
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- KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 description 1
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- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
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- 229910052723 transition metal Inorganic materials 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C269/06—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups by reactions not involving the formation of carbamate groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/49—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reaction with carbon monoxide
- C07C45/50—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reaction with carbon monoxide by oxo-reactions
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/10—Preparation of carboxylic acids or their salts, halides or anhydrides by reaction with carbon monoxide
- C07C51/14—Preparation of carboxylic acids or their salts, halides or anhydrides by reaction with carbon monoxide on a carbon-to-carbon unsaturated bond in organic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/313—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of doubly bound oxygen containing functional groups, e.g. carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/22—Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
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Abstract
本发明公开了一种铁催化羰基化三组分偶联反应合成ɑ,β‑不饱和酮的方法,该方法包括如下步骤:在含有碱性物质和铁类催化剂的溶液体系中,铁催化芳基卤代物、烯基硼酸与一氧化碳进行偶联反应,得到ɑ,β‑不饱和酮。该方法具有诸多优势:催化剂来源广泛、廉价易得且环境友好,反应介质来源广泛、廉价且环保,无需外加配体且活性好,使用亚计量的碱可以取得高的催化活性,反应选择性高,底物来源广泛且稳定,底物官能团相容性好且底物的适用范围广。在优化的反应条件之下,目标产品分离后产率可以达到95%。
Description
技术领域
本发明属于催化合成技术和精细化学品合成领域,更具体地,涉及一种铁催化羰基化三组分偶联反应合成ɑ,β-不饱和酮的方法,特别涉及一种无配体铁催化芳基卤代物、烯基硼酸与一氧化碳三组分偶联反应直接合成ɑ,β-不饱和酮的方法。
背景技术
ɑ,β-不饱和酮在有机合成中是一类非常重要的化合物,这种羰基化合物可用于各种合成策略的中间步骤,如Diels-Alder反应、Morita-Baylis-Hillman反应,同时,ɑ,β-不饱和酮也是合成精细化学品、药物和天然产物的常用原料。Claisen-Schmidt反应是合成ɑ,β-不饱和酮的经典方法,然而该方法需要用到强碱,且底物是含有羰基的化合物,导致ɑ,β-不饱和酮的合成缺乏多样性(Himansu S.Biswal etal.,ACS SustainableChem.Eng.2022,10,14271-14279)。过渡金属催化的羰基化方法很好的解决了这些问题:无需强碱参与反应;官能团相容性好;羰基源是廉价易得、原子经济性好的一氧化碳。目前,已有文献报道利用了Heck反应来羰基化合成ɑ,β-不饱和酮,然而该类方法只适用于合成1,3-二取代丙烯酮结构的ɑ,β-不饱和酮且需采用贵金属钯催化(Matthias Beller etal.,J.Am.Chem.Soc.2010,132,14596–14602)。
发明内容
发明目的:针对现有技术存在的问题,本发明提供一种铁催化羰基化三组分偶联反应合成ɑ,β-不饱和酮的方法,解决现有合成ɑ,β-不饱和酮的方法需要使用贵金属催化剂催化反应、需要强碱或过量的碱、合成方法单一、合成ɑ,β-不饱和酮种类单一等技术问题。
本发明利用铁类催化剂催化芳基卤代物、烯基硼酸与一氧化碳通过偶联反应合成ɑ,β-不饱和酮的方法,该方法具有显著的优势:催化剂来源广泛、廉价易得且环境友好,反应介质来源广泛、廉价且环保,无需外加配体且活性好,使用亚计量的碱可以取得高的催化活性,反应选择性高,底物来源广泛且稳定,底物官能团相容性好且底物的适用范围广。
技术方案:为了实现上述目的,本发明所述一种铁催化羰基化三组分偶联反应合成ɑ,β-不饱和酮的方法,在含有碱性物质和铁类催化剂的溶液体系中,芳基卤代物、烯基硼酸与一氧化碳进行偶联反应,得到ɑ,β-不饱和酮;
反应通式表示如下:
式中,X为溴或碘;
Ar为取代或者非取代的苯基、取代或者非取代的萘基、取代或者非取代的蒽基、取代或者非取代的菲基、取代或者非取代的芘基或取代或者非取代的杂芳基;
R1、R2和R3各自独立选自氢,或者选自C1~C10烷基,或者选自取代或非取代的苯基、取代或非取代的萘基、取代或非取代的蒽基、取代或非取代的菲基或取代或非取代的芘基。
其中,所述Ar为取代的苯基、萘基、蒽基、菲基、芘基或芳杂环基时,其含有的取代基为C1~C10烷基、苯基、C1~C10烷氧基、卤素取代基、羟基、硝基、羧基、氰基、三氟甲基、C2~C12酯基、N-叔丁氧羰基-L-丙氨酸基中至少一种;所述杂芳基为含N、O或S的五至十三元环的杂芳基。
其中,所述R1、R2或R3选自取代的苯基、萘基、蒽基、菲基或芘基时,其含有的取代基为C1~C10烷基、C1~C10烷氧基、苯基、卤素取代基、三氟甲基中至少一种,或者,R1和R2构成C5~C8的闭合脂肪环。
作为优选,本发明的ɑ,β-不饱和酮中Ar是由芳基卤代物引入的基团,其选择范围比较广,主要为取代或非取代的苯基、萘基、蒽基、菲基、芘基或芳杂环基,这些取代基都能获得较高的目标产物收率。Ar可以为苯基或稠环取代基,稠环取代基常见为萘基、蒽基、菲基或芘基。Ar还可以为芳杂环基,芳杂环基主要是含有氮、氧或硫中一种以上杂原子的芳杂环基,芳杂环基可以为五元环或六元环,具体例如噻吩基、吡啶基、异恶唑基等。Ar还可以为苯基、萘基、蒽基、菲基、芘基或芳杂环基衍生出来的基团,主要是在芳基或芳杂环基上进一步包含有常见的取代基,这些取代基可以为C1~C10烷基、苯基、C1~C10烷氧基、卤素取代基、羟基、硝基、羧基、氰基、三氟甲基、C2~C12酯基、N-叔丁氧羰基-L-丙氨酸基中至少一种,取代基的位置不受限制,取代基的数量也不受限制,但一般常见为1~2个取代基,当取代基选择C1~C10烷基时,可以为直链烷基,也可以为含支链的烷基,碳原子数超过3时,烷基还可以为环烷基,具体例如甲基、异丁基、环己基等;当取代基为C1~C10烷氧基时,可以为甲氧基、乙氧基、异丁氧基等;当取代基为卤素取代基时,可以选择氟、氯、溴等常见卤素取代基;当取代基为C2~C12酯基时,酯基中可以包含C1~C11饱和脂肪烃或不饱和脂肪烃,也可以包含其他常见的有机基团,如羟基、碳基等。
作为优选,本发明的ɑ,β-不饱和酮中R1、R2和R3是由烯基硼酸引入的基团,R1、R2和R3独立选自氢,或者选自C1~C10烷基,或选自取代或非取代的苯基、萘基、蒽基、菲基或芘基,或者,R1和R2构成C5~C8的闭合脂肪环。R1、R2和R3可以同时选择为氢或同时选择其他取代基团,也可以一个选自氢,另一个选自其他取代基团,其他取代基团选自取代或非取代的苯基、萘基、蒽基、菲基或芘基,还有一种特殊的情况,R1和R2可以为闭合脂肪环,脂肪环的碳原子数一般在5~8,脂肪环可以为饱和脂肪环也可以为不饱和脂肪环。R1、R2和R3选自取代的苯基、萘基、蒽基、菲基或芘基时,其含有的取代基为C1~C10烷基、C1~C10烷氧基、苯基、卤素取代基、三氟甲基中至少一种;取代基的位置不受限制,取代基的数量也不受限制,但一般常见为1~2个取代基,当取代基选择C1~C10烷基时,可以为直链烷基,也可以为含支链的烷基,碳原子数超过3时,烷基还可以为环烷基,具体例如甲基、异丁基、环己基等;当取代基为C1~C10烷氧基时,可以为甲氧基、乙氧基、异丁氧基等;当取代基为卤素取代基时,可以选择氟、氯、溴等常见卤素取代基。
其中,所述碱性物质选自氢氧化钠、氢氧化钾、氢氧化钙、碳酸钠、碳酸氢钠、碳酸钾、碳酸氢钾、碳酸锂、碳酸铯、磷酸钠、磷酸氢钠、磷酸氢二钠、磷酸钾、磷酸氢钾、醋酸钠、醋酸钾、特戊酸钠、特戊酸钾、氟化钾、四丁基氟化铵、三乙胺和二异丙基乙胺中至少一种。
优选地,碱性物质主要用来活化烯基硼酸,以提高烯基硼酸的转化效率。
其中,所述铁选自氯化亚铁、三氯化铁、乙酰丙酮亚铁、乙酰丙酮铁、三氟甲磺酸亚铁、三氟甲磺酸铁、1,3-二苯基丙二酮亚铁、1,3-二苯基丙二酮铁、苯甲酰丙酮亚铁、苯甲酰丙酮铁、铁氰化亚铁、铁氰化铁、醋酸亚铁、硫酸亚铁、硫酸铁、草酸亚铁、草酸铁、氟化亚铁、氟化铁、溴化亚铁、溴化铁、碘化亚铁、碘化铁、高氯酸铁(III)水合物和硝酸铁中至少一种。
其中,所述溶液体系采用聚乙二醇或者聚乙二醇和水溶剂作为溶剂。
作为优选,所述聚乙二醇为低聚聚乙二醇,其分子量为200~10000。低聚聚乙二醇的分子量更优选为低聚聚乙二醇的分子量为200~800。
其中,所述一氧化碳的压力为常压,提供羰基源。
其中,所述芳基卤代物、烯基硼酸、碱性物质和铁类催化剂的摩尔比为1:(1~2):(0.1~10):(0.001~10)。
其中,所述偶联反应的条件为:常压下,温度为50~150℃,时间为0.5~60小时。
本发明的芳基卤代物、烯基硼酸与一氧化碳通过偶联反应合成ɑ,β-不饱和酮的反应机理:首先,铁与一氧化碳原位形成羰基铁化物,紧接着在碱作用下与烯基硼试剂作用形成高亲核性的有机铁中间体。该中间体发生分子内一氧化碳迁移插入形成酰基铁物种。随后,芳基卤代物通过单电子转移过程与酰基铁物种发生氧化加成形成关键的酰基芳基铁中间体,紧接着发生还原消除给出目标产物。本发明的方法中使用的催化剂来源广泛、廉价易得且环境友好,反应介质来源广泛、廉价且环保,无需外加配体且活性好,使用亚计量的碱可以取得高的催化活性,反应选择性高,底物来源广泛且稳定,底物官能团相容性好且底物的适用范围广,使用铁催化即可完成反应。
本发明通过铁催化实现羰基化三组分偶联反应合成ɑ,β-不饱和酮,催化剂廉价易得、弱的亚计量碱可以使反应顺利进行,而现有ɑ,β-不饱和酮的合成方法需要用到贵金属钯催化,或需要使用强碱。
此外,铁催化活性通常不高,对于羰基化偶联反应实际非常困难,本发明通过特定的合成方法和反应条件,首次发现铁能催化高效该类反应。
有益效果:与现有技术相比,本发明具有如下优点:
(1)本发明提供了一种无需配体促进的铁催化羰基化三组分偶联反应合成ɑ,β-不饱和酮的方法,该方法具有催化剂廉价、来源广泛和环保的独特优势;反应常压进行且选择性高;弱的亚计量碱可以使反应顺利进行;
(2)本发明提供的合成ɑ,β-不饱和酮的方法简单易行和安全,可直接得到目标产物,在优化的反应条件之下,目标产品分离后产率可达到95%,是一种通用、高效、经济和环境友好的合成ɑ,β-不饱和酮的方法;
(3)本发明提供的ɑ,β-不饱和酮的合成方法中,利用低聚聚乙二醇及其水溶液作为溶剂可以显著提高铁催化羰基化的活性,同时利用碱抑制了非羰基化副产物的生成,使得该反应具有高选择性、官能团相容性好和适用范围广的优势。
具体实施方式
根据下述实施例,可以更好地理解本发明。然而,本领域的技术人员容易理解,实施例所描述的内容仅用于说明本发明,而不应当也不会限制权利要求书中所详细描述的本发明。
实施例中所述实验方法,如无特殊说明,均为常规方法;所述试剂和材料,如无特殊说明,均可从商业途径或通过现有技术简单制备获得。
实施例中的底物和产物的具体结构见表1。
本发明实施例中所用原料化合物以及合成的产物均为已知化合物,可以通过现有方法合成。
本发明实施例中以聚乙二醇作为反应溶剂,低分子量PEG为液体,高分子量的PEG是低熔点固体,加热为液体作为溶剂。
实施例1
化合物1:25mL反应瓶中依次加入氯化亚铁(0.05mmol),碳酸钠(0.25mmol),1a(0.5mmol),2a(0.6mmol)和聚乙二醇-400(2.0mL),并引入一个大气压的一氧化碳。反应混合物在100℃下反应3h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙醚V/V=10:3)得到产物1,其产率86%。
1H NMR(400MHz,CDCl3)δ8.37(d,J=8.8Hz,2H),8.16(d,J=8.8Hz,2H),7.86(d,J=15.6Hz,1H),7.69-7.67(m,2H),7.51(d,J=16.0Hz,1H),7.48-7.44ppm(m,3H);13C NMR(100MHz,CDCl3)δ189.0,150.0,146.8,143.0,134.2,131.2,129.4,129.1,128.7,123.8,121.2ppm.
实施例2
化合物2:25mL反应瓶中依次加入三氯化铁(0.05mmol),氢氧化钠(0.25mmol),1b(0.5mmol),2a(0.6mmol)和聚乙二醇-400(2.0mL),并引入一个大气压的一氧化碳。反应混合物在100℃下反应12h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙醚V/V=10:2)得到产物2,其产率75%。
实施例3
化合物3:25mL反应瓶中依次加入乙酰丙酮亚铁(0.05mmol),氢氧化钾(0.25mmol),1c(0.5mmol),2a(0.6mmol)和聚乙二醇-400(2.0mL),并引入一个大气压的一氧化碳。反应混合物在100℃下反应12h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙醚V/V=10:2)得到产物3,其产率85%。
1H NMR(400MHz,CDCl3)δ7.60-7.58(m,2H),7.53-7.51(m,1H),7.49(d,J=16.4Hz,1H),7.44-7.39(m,4H),7.31(d,J=7.6Hz,2H),7.16(d,J=16.0Hz,1H),2.47ppm(s,3H);13CNMR(100MHz,CDCl3)δ196.6,145.9,139.0,136.9,134.5,131.3,130.6,130.4,128.9,128.4,128.1,126.7,125.4,20.2ppm.
实施例4
化合物4:25mL反应瓶中依次加入乙酰丙酮铁(0.05mmol),氢氧化钙(0.25mmol),1d(0.5mmol),2a(0.6mmol)和聚乙二醇-400(2.0mL),并引入一个大气压的一氧化碳。反应混合物在100℃下反应12h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙醚V/V=10:2)得到产物4,其产率85%。
实施例5
化合物5:25mL反应瓶中依次加入三氟甲磺酸亚铁(0.05mmol),碳酸氢钠(0.25mmol),1e(0.5mmol),2a(0.5mmol)和聚乙二醇-400(2.0mL),并引入一个大气压的一氧化碳。反应混合物在100℃下反应12h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙醚V/V=10:3)得到产物5,其产率80%。
实施例6
化合物6:25mL反应瓶中依次加入三氟甲磺酸铁(0.05mmol),碳酸钾(0.25mmol),1f(0.3mmol),2a(0.5mmol)和聚乙二醇-400(2.0mL),并引入一个大气压的一氧化碳。反应混合物在100℃下反应12h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙醚V/V=10:3)得到产物6,其产率86%。
实施例7
化合物7:25mL反应瓶中依次加入1,3-二苯基丙二酮亚铁(0.05mmol),碳酸钾(0.25mmol),1g(0.5mmol),2a(1.0mmol)和聚乙二醇-400(2.0mL),并引入一个大气压的一氧化碳。反应混合物在100℃下反应12h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙醚V/V=10:2)得到产物7,其产率80%。
实施例8
化合物8:25mL反应瓶中依次加入1,3-二苯基丙二酮铁(0.05mmol),碳酸氢钾(0.25mmol),1h(0.5mmol),2a(1.0mmol)和聚乙二醇-400(2.0mL),并引入一个大气压的一氧化碳。随后,滴加双氧水(0.5mmol)。反应混合物在100℃下反应12h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙醚V/V=10:2)得到产物8,其产率80%。
实施例9
化合物9:5mL反应瓶中依次加入1,3-二苯基丙二酮铁(0.05mmol),碳酸锂(0.25mmol),1i(0.5mmol),2a(0.6mmol)和聚乙二醇-400(2.0mL),并引入一个大气压的一氧化碳。反应混合物在100℃下反应12h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙醚V/V=10:3)得到产物9,其产率75%。
实施例10
化合物10:5mL反应瓶中依次加入苯甲酰丙酮铁(0.05mmol),碳酸铯(0.25mmol),1j(0.25mmol),2a(0.6mmol)和聚乙二醇-400(2.0mL),并引入一个大气压的一氧化碳。反应混合物在100℃下反应12h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙醚V/V=10:2)得到产物10,其产率85%。
实施例11
化合物11:5mL反应瓶中依次加入铁氰化亚铁(0.05mmol),磷酸钠(0.25mmol),1k(0.5mmol),2a(0.6mmol)和聚乙二醇-400(2.0mL),并引入一个大气压的一氧化碳。反应混合物在100℃下反应13h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙醚V/V=10:2)得到产物11,其产率85%。
实施例12
化合物12:5mL反应瓶中依次加入铁氰化铁(0.05mmol),磷酸氢钠(0.375mmol),1l(0.5mmol),2a(0.6mmol)和聚乙二醇-200(2.0mL),并引入一个大气压的一氧化碳。反应混合物在100℃下反应12h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙醚V/V=10:3)得到产物12,其产率90%。
1H NMR(400MHz,CDCl3)δ8.11(d,J=8.8Hz,2H),7.86(d,J=15.6Hz,1H),7.83(d,J=8.4Hz,2H),7.68-7.66(m,2H),7.49(d,J=15.6Hz,1H),7.47-7.43ppm(m,3H);13C NMR(100MHz,CDCl3)δ189.1,146.6,141.4,134.3,132.5,131.1,129.1,128.8,128.6,121.0,118.0,115.9ppm.
实施例13
化合物13:5mL反应瓶中依次加入醋酸亚铁(0.05mmol),磷酸氢二钠(0.375mmol),1m(0.5mmol),2a(0.6mmol)和聚乙二醇-400(2.0mL),并引入一个大气压的一氧化碳。反应混合物在100℃下反应12h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙醚V/V=10:3)得到产物13,其产率93%。
1H NMR(400MHz,CDCl3)δ8.18(d,J=8.4Hz,2H),8.07(d,J=8.4Hz,2H),7.84(d,J=15.6Hz,1H),7.68-7.66(m,2H),7.53(d,J=15.6Hz,1H),7.45-7.44(m,3H),3.97ppm(s,3H);13C NMR(100MHz,CDCl3)δ190.0,166.2,145.7,141.5,134.5,133.4,130.8,129.8,129.0,128.5,128.3,121.7,52.4ppm.
实施例14
化合物14:5mL反应瓶中依次加入硫酸亚铁(0.05mmol),磷酸钾(0.25mmol),1n(0.5mmol),2a(0.6mmol)和聚乙二醇-400(2.0mL),并引入一个大气压的一氧化碳。反应混合物在100℃下反应12h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙醚V/V=10:2)得到产物14,其产率85%。
1H NMR(400MHz,CDCl3)δ8.07(d,J=9.2Hz,2H),7.83(d,J=15.6Hz,1H),7.68-7.65(m,2H),7.58(d,J=15.6Hz,1H),7.45–7.43(m,3H),7.01(d,J=9.2Hz,2H),3.91ppm(s,3H);13C NMR(100MHz,CDCl3)δ188.7,163.4,144.0,135.0,131.0,130.8,130.3,128.9,128.3,121.8,113.8,55.5ppm.
实施例15
化合物15:5mL反应瓶中依次加入硫酸铁(0.05mmol),磷酸钾(0.25mmol),1o(0.5mmol),2a(0.6mmol)和聚乙二醇-400(2.0mL),并引入一个大气压的一氧化碳。反应混合物在100℃下反应12h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙醚V/V=10:2)得到产物15,其产率73%。
1H NMR(400MHz,CDCl3)δ8.36(d,J=7.6Hz,1H),8.03(d,J=8.4Hz,1H),7.95-7.93(m,1H),7.81-7.79(m,1H),7.64(d,J=16.0Hz,1H),7.62-7.56(m,5H),7.45-7.41(m,3H),7.34ppm(d,J=16.0Hz,1H);13C NMR(100MHz,CDCl3)δ195.8,146.0,137.0,134.5,133.8,131.6,130.7,130.4,128.9,128.5,128.4,127.4,127.1,127.0,126.4,125.6,124.5ppm.
实施例16
化合物16:5mL反应瓶中依次加入草酸亚铁(0.05mmol),磷酸氢钾(0.25mmol),1p(0.5mmol),2a(0.6mmol)和聚乙二醇-400(2.0mL),并引入一个大气压的一氧化碳。反应混合物在100℃下反应24h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙醚V/V=10:2)得到产物16,其产率60%。
1H NMR(400MHz,CDCl3)δ8.20-8.19(m,1H),7.84(d,J=15.6Hz,1H),7.70-7.69(m,1H),7.66-7.64(m,2H),7.45-7.41(m,4H),7.39-7.37ppm(m,1H);13C NMR(100MHz,CDCl3)δ183.8,144.0,143.0,134.7,132.0,130.4,128.9,128.3,127.4,126.4,122.6ppm.
实施例17
化合物17:5mL反应瓶中依次加入草酸铁(0.05mmol),磷酸氢钾(0.25mmol),1q(0.5mmol),2a(0.6mmol)和聚乙二醇-400(2.0mL),并引入一个大气压的一氧化碳。反应混合物在100℃下反应4h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙醚V/V=10:3)得到产物17,其产率85%。
1H NMR(400MHz,CDCl3)δ7.67(d,J=7.6Hz,1H),7.60-7.57(m,2H),7.47-7.42(m,6H),7.38-7.34(m,1H),7.12ppm(d,J=16.0Hz,1H);13C NMR(100MHz,CDCl3)δ194.8,146.7,141.0,134.3,133.4,131.3,130.9,129.1,129.0,128.6,127.3,126.1,119.4ppm.
实施例18
化合物18:5mL反应瓶中依次加入氟化亚铁(0.05mmol),醋酸钠(0.25mmol),1r(0.5mmol),2a(0.6mmol)和聚乙二醇-400(2.0mL),并引入一个大气压的一氧化碳。反应混合物在100℃下反应12h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙醚V/V=10:2)得到产物18,其产率70%。
1H NMR(400MHz,CDCl3)δ7.57-7.55(m,2H),7.49-7.46(m,2H),7.43-7.41(m,3H),7.36(d,J=8.0Hz,1H),7.30-7.26(m,1H),7.10(d,J=16.4Hz,1H),3.23(dt,J=13.7,6.8Hz,1H),1.27(s,3H),1.25ppm(s,3H);13C NMR(100MHz,CDCl3)δ198.2,147.0,146.6,138.8,134.4,130.7,130.2,129.0,128.4,127.8,127.2,126.1,125.3,30.0,24.2ppm.
实施例19
化合物19:5mL反应瓶中依次加入氟化铁(0.05mmol),醋酸钾(0.25mmol),1s(0.5mmol),2a(0.6mmol)和聚乙二醇-400(2.0mL),并引入一个大气压的一氧化碳。反应混合物在100℃下反应12h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙醚V/V=10:2)得到产物19,其产率50%。
1H NMR(400MHz,CDCl3)δ7.54-7.52(m,2H),7.44-7.38(m,3H),7.20(d,J=15.6Hz,1H),6.95(d,J=15.6Hz,1H),6.91(s,2H),2.35(s,3H),2.21ppm(s,6H);13C NMR(100MHz,CDCl3)δ201.5,146.7,138.4,137.0,134.4,134.1,130.8,128.9,128.5,128.4,128.3,21.1,19.3ppm.
实施例20
化合物20:55mL反应瓶中依次加入溴化亚铁(0.05mmol),醋酸钾(0.25mmol),1t(0.5mmol),2a(0.6mmol)和聚乙二醇-400(2.0mL),并引入一个大气压的一氧化碳。反应混合物在100℃下反应12h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙醚V/V=10:2)得到产物20,其产率75%。
1H NMR(400MHz,CDCl3)δ7.71(d,J=15.6Hz,1H),7.62-7.60(m,2H),7.47-7.42(m,3H),7.13(d,J=15.6Hz,1H),2.70(s,3H),2.51ppm(s,3H);13CNMR(100MHz,CDCl3)δ185.3,173.0,159.1,144.6,134.3,130.9,129.1,128.4,124.3,117.4,13.9,12.1ppm.
实施例21
化合物21:5mL反应瓶中依次加入溴化铁(0.05mmol),特戊酸钠(0.875mmol),1u(0.5mmol),2a(0.6mmol)和聚乙二醇-400(2.0mL),并引入一个大气压的一氧化碳。反应混合物在120℃下反应24h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙醚V/V=10:4)得到产物21,其产率70%。
1H NMR(400MHz,CDCl3)δ8.03(d,J=8.8Hz,2H),7.84(d,J=15.6Hz,1H),7.66(dd,J=7.2,3.6Hz,2H),7.57(d,J=15.6Hz,1H),7.45-7.43(m,3H),6.98ppm(d,J=8.8Hz,2H);13C NMR(100MHz,CDCl3)δ189.2,160.4,144.4,134.9,131.2,130.9,130.5,128.9,128.4,121.8,115.6ppm;mp 162-163℃
实施例22
化合物22:5mL反应瓶中依次加入碘化亚铁(0.05mmol),特戊酸钠(0.875mmol),1v(0.5mmol),2a(0.6mmol),聚乙二醇-400(2.0mL)和水(2.0g),并引入一个大气压的一氧化碳。反应混合物在120℃下反应24h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙酸乙酯V/V=10:4)得到产物22,其产率65%。
1H NMR(400MHz,Acetone-d6)δ8.25(d,J=8.4Hz,2H),8.19(d,J=8.8Hz,2H),7.91(d,J=15.6Hz,1H),7.88-7.85(m,2H),7.83(d,J=15.6Hz,1H),7.49-7.43ppm(m,3H);13CNMR(100MHz,Acetone-d6)δ189.5,166.6,145.3,142.0,135.5,134.6,131.2,130.3,129.5,129.3,129.0,122.4ppm.
实施例23
化合物23:5mL反应瓶中依次加入碘化铁(0.05mmol),特戊酸钾(0.25mmol),1n(0.5mmol),2b(0.6mmol)和聚乙二醇-400(2.0mL),并引入一个大气压的一氧化碳。反应混合物在100℃下反应12h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙醚V/V=10:2)得到产物23,其产率87%。
实施例24
化合物24:5mL反应瓶中依次加入高氯酸铁(III)水合物(0.05mmol),氟化钾(0.25mmol),1n(0.5mmol),2c(0.6mmol)和聚乙二醇-400(2.0mL),并引入一个大气压的一氧化碳。反应混合物在100℃下反应12h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙醚V/V=10:2)得到产物24,其产率70%。
1H NMR(400MHz,CDCl3)δ8.07(d,J=8.8Hz,2H),7.81(d,J=15.6Hz,1H),7.75(d,J=8.0Hz,2H),7.68(d,J=8.4Hz,2H),7.63(d,J=16.0Hz,1H),7.02(d,J=8.8Hz,2H),3.92ppm(s,3H);13C NMR(100MHz,CDCl3)δ188.1,163.7,141.9,138.5,131.6(q,J=32.4Hz),130.9,130.7,128.4,125.8(q,J=3.8Hz),124.0,123.8(q,J=270.5Hz),113.9,55.5ppm.
实施例25
化合物25:5mL反应瓶中依次加入硝酸铁(0.05mmol),氟化钾(0.15mmol),1n(0.5mmol),2d(0.6mmol)和聚乙二醇-400(2.0mL),并引入一个大气压的一氧化碳。反应混合物在100℃下反应8h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙醚V/V=10:2)得到产物25,其产率85%。
实施例26
化合物26:5mL反应瓶中依次加入氯化亚铁(0.05mmol),四丁基氟化铵(0.25mmol),1n(0.5mmol),2e(0.6mmol)和聚乙二醇-400(2.0mL),并引入一个大气压的一氧化碳。反应混合物在100℃下反应12h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙醚V/V=10:2)得到产物26,其产率95%。
1H NMR(400MHz,CDCl3)δ7.95(d,J=8.8Hz,2H),6.95(d,J=15.6Hz,1H),6.73(m,1H),3.88(s,3H),2.20(d,J=1.0Hz,3H),2.02ppm(d,J=1.0Hz,2H);13C NMR(100MHz,CDCl3)δ190.3,162.9,155.2,132.1,130.4,121.2,113.6,55.4,27.9,21.1ppm.
实施例27
化合物27:5mL反应瓶中依次加入氯化亚铁(0.05mmol),三乙胺(0.25mmol),1n(0.5mmol),2f(0.6mmol)和聚乙二醇-400(2.0mL),并引入一个大气压的一氧化碳。反应混合物在100℃下反应18h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙醚V/V=10:2)得到产物27,其产率75%。
实施例28
化合物28:5mL反应瓶中依次加入氯化亚铁(0.05mmol),二异丙基乙胺(0.25mmol),1n(0.5mmol),2g(0.6mmol)和聚乙二醇-400(2.0mL),并引入一个大气压的一氧化碳。反应混合物在100℃下反应12h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙醚V/V=10:2)得到产物28,其产率70%。
实施例29
化合物29:5mL反应瓶中依次加入氯化亚铁(0.05mmol),碳酸钠(0.25mmol),1n(0.5mmol),2h(0.6mmol)和聚乙二醇-400(2.0mL),并引入一个大气压的一氧化碳。反应混合物在100℃下反应12h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙醚V/V=10:2)得到产物29,其产率75%。
实施例30
化合物30:5mL反应瓶中依次加入氯化亚铁(0.05mmol),二异丙基乙胺(0.25mmol),1f(0.5mmol),2h(0.6mmol)和聚乙二醇-400(2.0mL),并引入一个大气压的一氧化碳。反应混合物在100℃下反应12h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙醚V/V=10:2)得到产物30,其产率75%。
1H NMR(400MHz,CDCl3)δ7.98(d,J=8.4Hz,2H),7.82(d,J=15.6Hz,1H),7.56(d,J=8.0Hz,2H),7.49(d,J=8.0Hz,2H),7.46(d,J=15.6Hz,1H),7.25(d,J=8.0Hz,2H),2.42ppm(s,3H);13C NMR(100MHz,CDCl3)δ189.2,145.4,141.3,139.0,136.6,131.9,129.9,129.7,128.9,128.5,120.4,21.6ppm.
实施例31
化合物31:5mL反应瓶中依次加入氯化亚铁(0.05mmol),碳酸钠(0.75mmol),1c(0.5mmol),2h(0.6mmol)和聚乙二醇-400(2.0mL),并引入一个大气压的一氧化碳。反应混合物在100℃下反应12h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙醚V/V=10:2)得到产物31,其产率75%。
实施例32
化合物32:5mL反应瓶中依次加入氯化亚铁(0.05mmol),碳酸钠(0.75mmol),1n(0.5mmol),2i(0.5mmol)和聚乙二醇-400(2.0mL),并引入一个大气压的一氧化碳。反应混合物在100℃下反应8h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙醚V/V=10:2)得到产物32,其产率90%。
1H NMR(400MHz,CDCl3)δ7.70(d,J=8.8Hz,2H),6.93(d,J=8.8Hz,2H),6.52-6.50(m,1H),3.87(s,3H),2.44-2.41(m,2H),2.30-2.26(m,2H),1.78-1.72(m,2H),1.70-1.66ppm(m,2H);13C NMR(100MHz,CDCl3)δ197.2,162.4,141.6,138.7,131.6,131.0,113.3,55.4,25.9,24.3,22.1,21.7ppm.
实施例33
化合物33:5mL反应瓶中依次加入氯化亚铁(0.05mmol),碳酸钠(0.75mmol),1c(0.5mmol),2i(1.0mmol)和聚乙二醇-400(2.0mL),并引入一个大气压的一氧化碳。反应混合物在100℃下反应23h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙醚V/V=10:2)得到产物33,其产率91%。
1H NMR(400MHz,CDCl3)δ7.33-7.29(m,1H),7.22-7.17(m,3H),6.52-6.49(m,1H),2.44-2.41(m,2H),2.28(s,3H),2.25-2.21(m,2H),1.77-1.71(m,2H),1.69-1.65ppm(m,2H);13C NMR(100MHz,CDCl3)δ200.3,146.4,140.1,139.7,135.6,130.5,129.1,127.4,124.9,26.3,22.9,21.9,21.6,19.5ppm.
实施例34
化合物34:5mL反应瓶中依次加入氯化亚铁(0.05mmol),碳酸钠(0.75mmol),1f(0.5mmol),2i(0.6mmol)和聚乙二醇-200(2.0mL),并引入一个大气压的一氧化碳。反应混合物在100℃下反应5h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙醚V/V=10:3)得到产物34,其产率90%。
1H NMR(400MHz,CDCl3)δ7.60(d,J=8.4Hz,2H),7.41(d,J=8.4Hz,2H),6.58-6.43(m,1H),2.44-2.40(m,2H),2.31-2.27(m,2H),1.78-1.72(m,2H),1.72-1.66ppm(m,2H);13CNMR(100MHz,CDCl3)δ196.9,144.2,138.6,137.6,136.9,130.6,128.3,26.1,23.9,21.9,21.6ppm.
实施例35
化合物35:5mL反应瓶中依次加入氯化亚铁(0.05mmol),碳酸钠(0.25mmol),1n(0.5mmol),2j(0.6mmol)和聚乙二醇-400(2.0mL),并引入一个大气压的一氧化碳。反应混合物在100℃下反应12h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙醚V/V=10:2)得到产物35,其产率65%。
1H NMR(400MHz,CDCl3)δ7.94(d,J=9.2Hz,2H),7.46-7.43(m,2H),7.38-7.33(m,3H),6.93(d,J=9.2Hz,2H),6.02(s,1H),5.58(s,1H),3.88ppm(s,3H);13C NMR(100MHz,CDCl3)δ196.3,163.7,148.4,137.1,132.4,129.8,128.6,128.3,126.8,119.0,113.7,55.5ppm.
实施例36
化合物36:5mL反应瓶中依次加入氯化亚铁(0.05mmol),碳酸钠(0.25mmol),1w(0.5mmol),2a(0.6mmol)和聚乙二醇-8000(2.0mL),并引入一个大气压的一氧化碳。反应混合物在100℃下反应24h。反应结束,加入饱和食盐水10mL,并用乙醚萃取(10mL×3),合并有机相,减压蒸除溶剂后,直接层析分离(石油醚:乙酸乙酯V/V=10:4)得到产物36,其产率50%。
1H NMR(400MHz,CDCl3)δ7.99(d,J=8.0Hz,2H),7.83(d,J=15.6Hz,1H),7.67-7.64(m,2H),7.54(d,J=15.6Hz,1H),7.44-7.42(m,3H),7.36(d,J=7.2Hz,2H),5.10-5.08(m,1H),4.69-4.68(m,1H),3.34-3.15(m,2H),1.44ppm(s,9H);13C NMR(100MHz,CDCl3)δ190.3,175.0,155.3,145.0,141.6,136.7,134.8,130.6,129.8,128.9,128.8,128.5,121.8,80.4,54.0,37.9,28.2ppm.
实施例1~36的原料和产物结构式及对应的实验结果如下表1所示:
表1铁催化羰基化合成ɑ,β-不饱和酮
实施例37
实施例37与实施例26的方法相同,不同之处在于:芳基卤代物、烯基硼酸、碱性物质和铁类催化剂的摩尔比为1:1:0.1:0.001。
实施例38
实施例38与实施例26的方法相同,不同之处在于:芳基卤代物、烯基硼酸、碱性物质和铁类催化剂的摩尔比为1:2:10:10。
实施例39
实施例39与实施例26的方法相同,不同之处在于:溶剂(聚乙二醇-400和水),有机溶剂与水的质量比为1:0.1。
实施例40
实施例40与实施例26的方法相同,不同之处在于:溶剂(聚乙二醇-400和水),有机溶剂与水的质量比为1:5。
实施例41
实施例41与实施例26的方法相同,不同之处在于:反应的温度为50℃、时间为60小时。
实施例42
实施例42与实施例26的方法相同,不同之处在于:反应的温度为150℃、时间为0.5小时。
实施例43
实施例43与实施例26的方法相同,不同之处在于:聚乙二醇为其分子量为200。
实施例44
实施例44与实施例26的方法相同,不同之处在于:聚乙二醇为其分子量为10000。
对比例1
对比例1与实施例26的方法相同,不同之处在于:不加入铁催化剂,目标产物产率为0。
对比例2
对比例2与实施例26的方法相同,不同之处在于:加入醋酸钯做催化剂,目标产物产率为48%。
对比例3
对比例3与实施例26的方法相同,不同之处在于:不加入碱性物质,目标产物产率为0。
对比例4
对比例4与实施例26的方法相同,不同之处在于:加入水替代聚乙二醇-400,有痕量目标产物生成。
Claims (10)
2.根据权利要求1所述的铁催化羰基化三组分偶联反应合成ɑ,β-不饱和酮的方法,其特征在于,所述Ar为取代的苯基、萘基、蒽基、菲基、芘基或芳杂环基时,其含有的取代基为C1~C10烷基、苯基、C1~C10烷氧基、卤素取代基、羟基、硝基、羧基、氰基、三氟甲基、C2~C12酯基、N-叔丁氧羰基-L-丙氨酸基中至少一种;所述杂芳基为含N、O或S的五至十三元环的杂芳基。
3.根据权利要求1所述的铁催化羰基化三组分偶联反应合成ɑ,β-不饱和酮的方法,其特征在于,所述R1、R2或R3选自取代的苯基、萘基、蒽基、菲基或芘基时,其含有的取代基为C1~C10烷基、C1~C10烷氧基、苯基、卤素取代基、三氟甲基中至少一种,或者,R1和R2构成C5~C8的闭合脂肪环。
4.根据权利要求1所述的铁催化羰基化三组分偶联反应合成ɑ,β-不饱和酮的方法,其特征在于,所述碱性物质选自氢氧化钠、氢氧化钾、氢氧化钙、碳酸钠、碳酸氢钠、碳酸钾、碳酸氢钾、碳酸锂、碳酸铯、磷酸钠、磷酸氢钠、磷酸氢二钠、磷酸钾、磷酸氢钾、醋酸钠、醋酸钾、特戊酸钠、特戊酸钾、氟化钾、四丁基氟化铵、三乙胺和二异丙基乙胺中至少一种。
5.根据权利要求1所述的铁催化羰基化三组分偶联反应合成ɑ,β-不饱和酮的方法,其特征在于,所述铁选自氯化亚铁、三氯化铁、乙酰丙酮亚铁、乙酰丙酮铁、三氟甲磺酸亚铁、三氟甲磺酸铁、1,3-二苯基丙二酮亚铁、1,3-二苯基丙二酮铁、苯甲酰丙酮亚铁、苯甲酰丙酮铁、铁氰化亚铁、铁氰化铁、醋酸亚铁、硫酸亚铁、硫酸铁、草酸亚铁、草酸铁、氟化亚铁、氟化铁、溴化亚铁、溴化铁、碘化亚铁、碘化铁、高氯酸铁(III)水合物和硝酸铁中至少一种。
6.根据权利要求1所述的铁催化羰基化三组分偶联反应合成ɑ,β-不饱和酮的方法,其特征在于,所述溶液体系优选采用聚乙二醇或者聚乙二醇和水溶剂作为溶剂。
7.根据权利要求6所述的铁催化羰基化三组分偶联反应合成ɑ,β-不饱和酮的方法,其特征在于,所述聚乙二醇为低聚聚乙二醇,其分子量为200~10000。
8.根据权利要求1所述的铁催化羰基化三组分偶联反应合成ɑ,β-不饱和酮的方法,其特征在于,所述一氧化碳的压力为常压。
9.根据权利要求1所述的铁催化羰基化三组分偶联反应合成ɑ,β-不饱和酮的方法,其特征在于,所述芳基卤代物、烯基硼酸、碱性物质和铁类催化剂的摩尔比为1:(1~2):(0.1~10):(0.001~10)。
10.根据权利要求1所述的铁催化羰基化三组分偶联反应合成ɑ,β-不饱和酮的方法,其特征在于,所述偶联反应的条件为:常压下,温度为50~150℃,时间为0.5~60小时。
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