CN113861002B - Method for preparing aromatic ketone compound by catalytic oxidation of aromatic alcohol without metal catalytic system - Google Patents
Method for preparing aromatic ketone compound by catalytic oxidation of aromatic alcohol without metal catalytic system Download PDFInfo
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- CN113861002B CN113861002B CN202111285670.9A CN202111285670A CN113861002B CN 113861002 B CN113861002 B CN 113861002B CN 202111285670 A CN202111285670 A CN 202111285670A CN 113861002 B CN113861002 B CN 113861002B
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- Prior art keywords
- cycloalkyl
- alkyl
- aryl
- group
- membered
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- -1 aromatic ketone compound Chemical class 0.000 title claims abstract description 92
- 238000000034 method Methods 0.000 title claims abstract description 34
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 title claims abstract description 21
- 230000003197 catalytic effect Effects 0.000 title abstract description 12
- 230000003647 oxidation Effects 0.000 title abstract description 8
- 238000007254 oxidation reaction Methods 0.000 title abstract description 8
- 229910052751 metal Inorganic materials 0.000 title description 5
- 239000002184 metal Substances 0.000 title description 5
- 238000006243 chemical reaction Methods 0.000 claims abstract description 54
- 230000001590 oxidative effect Effects 0.000 claims abstract description 13
- 239000007800 oxidant agent Substances 0.000 claims abstract description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 10
- 239000001301 oxygen Substances 0.000 claims abstract description 10
- 238000004519 manufacturing process Methods 0.000 claims abstract description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 78
- 125000000623 heterocyclic group Chemical group 0.000 claims description 66
- 125000000217 alkyl group Chemical group 0.000 claims description 56
- 125000003118 aryl group Chemical group 0.000 claims description 50
- 125000001072 heteroaryl group Chemical group 0.000 claims description 46
- 125000003545 alkoxy group Chemical group 0.000 claims description 36
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 34
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 30
- 229910052736 halogen Inorganic materials 0.000 claims description 27
- 150000002367 halogens Chemical class 0.000 claims description 27
- 229910052799 carbon Inorganic materials 0.000 claims description 21
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 21
- 239000002904 solvent Substances 0.000 claims description 20
- 150000007530 organic bases Chemical group 0.000 claims description 19
- 125000001424 substituent group Chemical group 0.000 claims description 18
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 17
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 15
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 14
- 239000003054 catalyst Substances 0.000 claims description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- 238000004440 column chromatography Methods 0.000 claims description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 12
- 239000002994 raw material Substances 0.000 claims description 11
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 10
- 238000010791 quenching Methods 0.000 claims description 10
- 230000000171 quenching effect Effects 0.000 claims description 10
- 238000003756 stirring Methods 0.000 claims description 9
- 238000001704 evaporation Methods 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 7
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 claims description 6
- LZWQNOHZMQIFBX-UHFFFAOYSA-N lithium;2-methylpropan-2-olate Chemical compound [Li+].CC(C)(C)[O-] LZWQNOHZMQIFBX-UHFFFAOYSA-N 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 125000000304 alkynyl group Chemical group 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- AZVCGYPLLBEUNV-UHFFFAOYSA-N lithium;ethanolate Chemical compound [Li+].CC[O-] AZVCGYPLLBEUNV-UHFFFAOYSA-N 0.000 claims description 3
- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 claims description 3
- 125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- 125000004043 oxo group Chemical group O=* 0.000 claims description 3
- RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 claims description 3
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 3
- 125000003944 tolyl group Chemical group 0.000 claims description 2
- 239000010814 metallic waste Substances 0.000 abstract description 2
- 231100000614 poison Toxicity 0.000 abstract description 2
- 239000003440 toxic substance Substances 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- 125000006413 ring segment Chemical group 0.000 description 16
- 229910052757 nitrogen Inorganic materials 0.000 description 15
- NTPLXRHDUXRPNE-UHFFFAOYSA-N 4-methoxyacetophenone Chemical compound COC1=CC=C(C(C)=O)C=C1 NTPLXRHDUXRPNE-UHFFFAOYSA-N 0.000 description 12
- 125000004432 carbon atom Chemical group C* 0.000 description 12
- 125000003367 polycyclic group Chemical group 0.000 description 12
- 125000002619 bicyclic group Chemical group 0.000 description 11
- 239000003153 chemical reaction reagent Substances 0.000 description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 11
- 125000005842 heteroatom Chemical group 0.000 description 10
- MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 description 9
- 238000004809 thin layer chromatography Methods 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
- 125000000000 cycloalkoxy group Chemical group 0.000 description 8
- 125000004438 haloalkoxy group Chemical group 0.000 description 8
- 125000001188 haloalkyl group Chemical group 0.000 description 8
- 125000005844 heterocyclyloxy group Chemical group 0.000 description 8
- 125000002950 monocyclic group Chemical group 0.000 description 8
- 239000003208 petroleum Substances 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 7
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 7
- 238000000605 extraction Methods 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- 229910052717 sulfur Chemical group 0.000 description 7
- 239000011593 sulfur Chemical group 0.000 description 7
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 6
- 238000001035 drying Methods 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 239000000010 aprotic solvent Substances 0.000 description 5
- 125000004429 atom Chemical group 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 238000005303 weighing Methods 0.000 description 5
- IUUULXXWNYKJSL-UHFFFAOYSA-N 4-methoxy-alpha-methylbenzyl alcohol Chemical compound COC1=CC=C(C(C)O)C=C1 IUUULXXWNYKJSL-UHFFFAOYSA-N 0.000 description 4
- 239000000470 constituent Substances 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 4
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- 125000003003 spiro group Chemical group 0.000 description 4
- 150000003457 sulfones Chemical class 0.000 description 4
- 150000003462 sulfoxides Chemical class 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- VXGJFMHAPUVWSB-UHFFFAOYSA-N 2-methyl-1-phenylpentan-1-one Chemical compound CCCC(C)C(=O)C1=CC=CC=C1 VXGJFMHAPUVWSB-UHFFFAOYSA-N 0.000 description 3
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 3
- 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- YLQWCDOCJODRMT-UHFFFAOYSA-N fluoren-9-one Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3C2=C1 YLQWCDOCJODRMT-UHFFFAOYSA-N 0.000 description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 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
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 125000002524 organometallic group Chemical group 0.000 description 3
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 125000005918 1,2-dimethylbutyl group Chemical group 0.000 description 2
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000005916 2-methylpentyl group Chemical group 0.000 description 2
- 125000005917 3-methylpentyl group Chemical group 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- 150000002739 metals Chemical class 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- WAPNOHKVXSQRPX-UHFFFAOYSA-N 1-phenylethanol Chemical compound CC(O)C1=CC=CC=C1 WAPNOHKVXSQRPX-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 125000003660 2,3-dimethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000003764 2,4-dimethylpentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- CRBHXDCYXIISFC-UHFFFAOYSA-N 2-(Trimethylammonio)ethanolate Chemical compound C[N+](C)(C)CC[O-] CRBHXDCYXIISFC-UHFFFAOYSA-N 0.000 description 1
- CJNZAXGUTKBIHP-UHFFFAOYSA-N 2-iodobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1I CJNZAXGUTKBIHP-UHFFFAOYSA-N 0.000 description 1
- AKMRXUUGAJOMFO-UHFFFAOYSA-N 2-methyl-1-phenylpentan-1-ol Chemical compound CCCC(C)C(O)C1=CC=CC=C1 AKMRXUUGAJOMFO-UHFFFAOYSA-N 0.000 description 1
- 125000003229 2-methylhexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004337 3-ethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003469 3-methylhexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 238000005675 Corey-Kim oxidation reaction Methods 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 238000006809 Jones oxidation reaction Methods 0.000 description 1
- 238000006633 Ley oxidation reaction Methods 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 229920000433 Lyocell Polymers 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 241000208125 Nicotiana Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- JWIPGAFCGUDKEY-UHFFFAOYSA-L O[Cr](Cl)(=O)=O.C1=CC=NC=C1 Chemical compound O[Cr](Cl)(=O)=O.C1=CC=NC=C1 JWIPGAFCGUDKEY-UHFFFAOYSA-L 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000008365 aromatic ketones Chemical class 0.000 description 1
- 125000000732 arylene group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- DUEPRVBVGDRKAG-UHFFFAOYSA-N carbofuran Chemical compound CNC(=O)OC1=CC=CC2=C1OC(C)(C)C2 DUEPRVBVGDRKAG-UHFFFAOYSA-N 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- LQEJKDNALLXRCT-UHFFFAOYSA-N chloroform;toluene Chemical compound ClC(Cl)Cl.CC1=CC=CC=C1 LQEJKDNALLXRCT-UHFFFAOYSA-N 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000002188 cycloheptatrienyl group Chemical group C1(=CC=CC=CC1)* 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000003678 cyclohexadienyl group Chemical group C1(=CC=CCC1)* 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 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 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- VRLDVERQJMEPIF-UHFFFAOYSA-N dbdmh Chemical compound CC1(C)N(Br)C(=O)N(Br)C1=O VRLDVERQJMEPIF-UHFFFAOYSA-N 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229910001882 dioxygen Inorganic materials 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- AFMVESZOYKHDBJ-UHFFFAOYSA-N fluoren-9-ol Chemical compound C1=CC=C2C(O)C3=CC=CC=C3C2=C1 AFMVESZOYKHDBJ-UHFFFAOYSA-N 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 125000005549 heteroarylene group Chemical group 0.000 description 1
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 1
- 239000002638 heterogeneous catalyst Substances 0.000 description 1
- 239000002815 homogeneous catalyst Substances 0.000 description 1
- BNSOYWDFFBDEFB-UHFFFAOYSA-L hydroxy-(hydroxy(dioxo)chromio)oxy-dioxochromium;pyridine Chemical compound C1=CC=NC=C1.O[Cr](=O)(=O)O[Cr](O)(=O)=O BNSOYWDFFBDEFB-UHFFFAOYSA-L 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000779 smoke Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical compound [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
- IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- OSBSFAARYOCBHB-UHFFFAOYSA-N tetrapropylammonium Chemical compound CCC[N+](CCC)(CCC)CCC OSBSFAARYOCBHB-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- 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
- C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
- C07C45/32—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with molecular oxygen
- C07C45/37—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with molecular oxygen of >C—O—functional groups to >C=O groups
- C07C45/39—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with molecular oxygen of >C—O—functional groups to >C=O groups being a secondary hydroxyl group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
- C07C2603/10—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings
- C07C2603/12—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings only one five-membered ring
- C07C2603/18—Fluorenes; Hydrogenated fluorenes
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present disclosure relates to a method for preparing aromatic ketone compounds by oxidizing aromatic alcohol compounds in a metal-free catalytic system, wherein the method uses air or oxygen widely existing in nature as an oxidant for oxidation, thereby reducing the generation of reaction metal waste. The method disclosed by the invention avoids the generation of toxic substances, is environment-friendly, simple, efficient, can be carried out at normal temperature and normal pressure, has mild reaction conditions, is easy to control in operation, is safe and reliable, has low cost, and can lay a foundation for the later industrialized mass production.
Description
Technical Field
The present disclosure belongs to the technical field of chemical synthesis, and in particular relates to a method for preparing aromatic ketone compounds by oxidizing aromatic alcohol compounds by a metal-free catalytic system.
Background
The aromatic ketone compound has important significance in the field of pharmaceutical chemical industry, and a large number of compounds in the existing medicines and medicine intermediates in the market contain aromatic ketone bonds, so that the efficient synthesis of the aromatic ketone compound has important significance and prospect for the chemical industry. At present, aromatic ketones are mainly prepared by taking aromatic alcohols as raw materials, wherein the raw materials comprise chromium-based systems CrO 3/H2SO4 (Jones oxidation), crO 3/py2 (Kolin oxidation), pyridine chlorochromate (Corey oxidation) or pyridine dichromate, a high-valence iodine reagent [ Dess-Martin periodinane or o-iodobenzoic acid, corey-Kim reagent, oppenauer reagent, manganese dioxide or tetrapropylammonium perruthenate (Ley-Griffith reagent). The organometallic reagents used in the above method are too active, so that the selectivity of the reaction sites is poor, and the organometallic reagents cannot carry active functional groups, thereby greatly limiting the application of the organometallic reagents in organic synthesis.
Recently, many other homogeneous and heterogeneous catalysts have been developed for the oxidation of alcohols, but most of these catalysts involve metals to increase catalytic activity, such as Cu, ru, pd, au and the like. Metal-free catalytic systems are currently mainly focused on TEMPO systems. For example TEMPO/polymer bound halogenate (I), TEMPO/Br 2/NaNO2, TEMPO/1, 3-dibromo-5, 5-dimethylhydantoin/NaNO 2, TEMPO/HBr/t-butyl nitrite, TEMPO/HCl/NaNO 2 and [ imim-TEMPO ] +X-/[imim-COOH]+X-/NaNO2 ] (imim-cooh=1-carboxymethyl-3-methylimidazole chloride) have been widely used for the aerobic oxidation of alcohols to carbonyl compounds. However, the use of the above-mentioned oxidizing agents in equal amounts produces almost equal amounts of waste derived from the oxidizing agents, which causes a certain pollution to the environment, and TEMPO systems are not widely used, on the one hand, relatively expensive, difficult to separate and sometimes require special operations. In addition, their relatively large structural dimensions further reduce their applicability in the fine chemical industry due to steric hindrance.
Meanwhile, the exploration of molecular oxygen and even air as terminal oxidants can further solve the above-mentioned disadvantageous problems, because it only produces water as a byproduct, and the use of non-cost atmosphere as an oxidant is more suitable for developing green and environment-friendly processes. In view of the fact that most of the catalytic systems reported at present are related to metals and/or that the catalyst synthesis and reaction processes are cumbersome, it is still urgent to explore an environment-friendly, simple, efficient, mild, metal-free catalytic system.
Disclosure of Invention
Problems to be solved by the invention
In order to solve the problems in the prior art, the present disclosure provides a method for preparing aromatic ketone compounds by oxidizing aromatic alcohol compounds with the participation of a metal-free catalytic system, which is environment-friendly, simple, efficient, mild in reaction condition, easy to control in operation, safe and reliable.
Solution for solving the problem
A process for preparing aromatic ketone compound features that the aromatic alcohol as raw material is reacted in the presence of catalyst and oxidant to obtain aromatic ketone compound,
The catalyst is an organic base, and the catalyst is an organic base,
The oxidant is air or oxygen;
The reaction process is as follows:
wherein A 1 is selected from N and C-R 1;
A 2 is selected from N and C-R 2;
A 3 is selected from N and C-R 3;
a 4 is selected from N and C-R 4;
a 5 is selected from N and C-R 5;
r 1、R2、R3、R4、R5 is each independently selected from the group consisting of hydrogen, halogen, alkyl, alkoxy, alkenyl, alkynyl, cyano, hydroxy, nitro, oxo, cycloalkyl, heterocyclyl, aryl, and heteroaryl, wherein the alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more substituents selected from the group consisting of halogen, alkyl, alkoxy, cyano, amino, nitro, hydroxy, hydroxyalkyl, carboxy, cycloalkyl, heterocyclyl, aryl, and heteroaryl;
R 6 is selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more substituents selected from the group consisting of halogen, alkyl, alkoxy, cyano, amino, nitro, hydroxy, hydroxyalkyl, carboxy, cycloalkyl, heterocyclyl, aryl, and heteroaryl;
Or R 5、R6 and the carbon to which it is attached form cycloalkyl, heterocyclyl, wherein said cycloalkyl, heterocyclyl is optionally substituted with one or more substituents selected from the group consisting of halogen, alkyl, alkoxy, cyano, amino, nitro, hydroxy, hydroxyalkyl, carboxyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
Or R 1、R6 and the carbon to which it is attached form cycloalkyl, heterocyclyl, wherein said cycloalkyl, heterocyclyl is optionally substituted with one or more substituents selected from the group consisting of halogen, alkyl, alkoxy, cyano, amino, nitro, hydroxy, hydroxyalkyl, carboxyl, cycloalkyl, heterocyclyl, aryl and heteroaryl.
Further, the organic base is selected from one or more of lithium tert-butoxide, sodium tert-butoxide, potassium tert-butoxide, lithium tert-amyl alcohol, sodium tert-amyl alcohol, potassium tert-amyl alcohol, sodium ethoxide, potassium ethoxide and lithium ethoxide; preferably one or more of lithium tert-butoxide, sodium tert-butoxide and potassium tert-butoxide; more preferably sodium tert-butoxide.
Further, the reaction is carried out in a solvent selected from aprotic solvents; preferably one or two of toluene, ethylbenzene, mesitylene, chlorobenzene, dichloromethane and chloroform; toluene is more preferred.
Further, the reaction temperature is 0 to 50 ℃, preferably room temperature.
Further, the molar ratio of the raw material aromatic alcohol to the organic base is 1:0.5-5; preferably 1:2.5.
Further, each R 1、R2、R3、R4、R5 is independently selected from hydrogen, halogen, alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl, and heteroaryl; preferably hydrogen, alkyl, alkoxy and aryl; more preferred are hydrogen, C 1-C10 alkyl, C 1-C10 alkoxy and C 6-C12 aryl.
Further, the R 6 is selected from alkyl, cycloalkyl, heterocyclyl, and aryl; preferably C 1-C10 alkyl and C 6-C12 aryl; more preferably a C 1-C6 alkyl group.
Further, the R 5、R6 and the carbon to which it is attached form cycloalkyl, which cycloalkyl is optionally substituted with phenyl; or R 1、R6 and the carbon to which it is attached form cycloalkyl, which cycloalkyl is optionally substituted with phenyl.
Further, the raw aromatic alcohol is selected from
Further, the reaction process is that raw materials of aromatic alcohol, a catalyst and a solvent are placed in a reaction vessel, and are stirred and reacted in an open mode, and the product of aromatic ketone compound is obtained after post-treatment; preferably, the post-treatment step is to add acid quenching after the reaction is completed, extract with organic solvent, evaporate the solvent and purify by column chromatography to obtain the product.
ADVANTAGEOUS EFFECTS OF INVENTION
The method for preparing aromatic ketone compounds by oxidizing aromatic alcohol compounds avoids using a metal catalytic system, utilizes air or oxygen widely existing in nature as an oxidant for oxidation, and reduces the generation of reaction metal wastes. The method disclosed by the invention avoids the generation of toxic substances, is environment-friendly, simple, efficient, can be carried out at normal temperature and normal pressure, has mild reaction conditions, is easy to control in operation, is safe and reliable, has low cost, and can lay a foundation for the later industrialized mass production. Meanwhile, the preparation method disclosed by the invention has high reaction yield and the obtained product has high purity.
Drawings
Fig. 1: 1 H NMR spectrum of acetophenone prepared in example 1.
Fig. 2: 13 C NMR spectrum of acetophenone prepared in example 1.
Fig. 3: 1 H NMR spectrum of 4-methoxyacetophenone prepared in example 2.
Fig. 4: 13 C NMR spectrum of 4-methoxyacetophenone prepared in example 2.
Fig. 5: 1 H NMR Spectrometry of 2-methyl-1-phenylpentan-1-one obtained in example 3.
Fig. 6: 13 C NMR Spectrometry of 2-methyl-1-phenylpentan-1-one obtained in example 3.
Fig. 7: 1 H NMR spectrum of 9-fluorenone prepared in example 4.
Fig. 8: 13 C NMR spectrum of 9-fluorenone prepared in example 4.
Detailed Description
In order to make the technical scheme and the beneficial effects of the present disclosure more obvious and understandable, the following detailed description is given by way of example only. Wherein the drawings are not necessarily to scale, and wherein local features may be exaggerated or reduced to more clearly show details of the local features; unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs.
The disclosure provides a method for preparing aromatic ketone compounds, which is characterized in that raw material aromatic alcohol reacts in the presence of a catalyst and an oxidant to obtain aromatic ketone compounds,
The catalyst is an organic base, and the catalyst is an organic base,
The oxidant is air or oxygen;
The reaction process is as follows:
wherein A 1 is selected from N and C-R 1;
A 2 is selected from N and C-R 2;
A 3 is selected from N and C-R 3;
a 4 is selected from N and C-R 4;
a 5 is selected from N and C-R 5;
r 1、R2、R3、R4、R5 is each independently selected from the group consisting of hydrogen, halogen, alkyl, alkoxy, alkenyl, alkynyl, cyano, hydroxy, nitro, oxo, cycloalkyl, heterocyclyl, aryl, and heteroaryl, wherein the alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more substituents selected from the group consisting of halogen, alkyl, alkoxy, cyano, amino, nitro, hydroxy, hydroxyalkyl, carboxy, cycloalkyl, heterocyclyl, aryl, and heteroaryl;
R 6 is selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more substituents selected from the group consisting of halogen, alkyl, alkoxy, cyano, amino, nitro, hydroxy, hydroxyalkyl, carboxy, cycloalkyl, heterocyclyl, aryl, and heteroaryl;
Or R 5、R6 and the carbon to which it is attached form cycloalkyl, heterocyclyl, wherein said cycloalkyl, heterocyclyl is optionally substituted with one or more substituents selected from the group consisting of halogen, alkyl, alkoxy, cyano, amino, nitro, hydroxy, hydroxyalkyl, carboxyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
Or R 1、R6 and the carbon to which it is attached form cycloalkyl, heterocyclyl, wherein said cycloalkyl, heterocyclyl is optionally substituted with one or more substituents selected from the group consisting of halogen, alkyl, alkoxy, cyano, amino, nitro, hydroxy, hydroxyalkyl, carboxyl, cycloalkyl, heterocyclyl, aryl and heteroaryl.
In certain embodiments, the organic base is selected from one or more of lithium t-butoxide, sodium t-butoxide, potassium t-butoxide, sodium ethoxide, potassium ethoxide, lithium ethoxide, and the like.
In certain embodiments, the organic base is selected from one or more of lithium t-butoxide, sodium t-butoxide, potassium t-butoxide, and the like.
In certain embodiments, the organic base is selected from sodium t-butoxide.
In certain embodiments, the reaction is performed in a solvent.
In certain embodiments, the solvent is selected from aprotic solvents.
In certain embodiments, the aprotic solvent is selected from one or both of toluene, ethylbenzene, mesitylene, chlorobenzene, methylene chloride, chloroform, and the like.
In certain embodiments, the aprotic solvent is selected from one or both of toluene and chlorobenzene.
In certain embodiments, the aprotic solvent is selected from toluene.
In certain embodiments, the reaction temperature is from 0 to 50 ℃.
In certain embodiments, the reaction temperature is from 10 to 30 ℃.
In certain embodiments, the reaction temperature is room temperature.
In certain embodiments, the molar ratio of the starting aromatic alcohol to the organic base is from 1:0.5 to 5.
In certain embodiments, the molar ratio of the starting aromatic alcohol to the organic base is from 1:1 to 3.
In certain embodiments, the molar ratio of the starting aromatic alcohol to the organic base is 1:2.5.
In certain embodiments, the reaction time of the reaction is from 0.5 to 12 hours.
In certain embodiments, the reaction time of the reaction is 0.5h.
In certain embodiments, each R 1、R2、R3、R4、R5 is independently selected from hydrogen, halogen, alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl, and heteroaryl; preferred are hydrogen, alkyl, alkoxy and aryl.
In certain embodiments, each of the R 1、R2、R3、R4、R5 is independently selected from the group consisting of hydrogen, C 1-C10 alkyl, C 1-C10 alkoxy, and C 6-C12 aryl.
In certain embodiments, each R 1、R2、R3、R4、R5 is independently selected from hydrogen, C 1-C3 alkyl, and C 1-C3 alkoxy.
In certain embodiments, each R 1、R2、R3、R4、R5 is independently selected from hydrogen, methyl, ethyl, methoxy, and ethoxy.
In certain embodiments, the R 6 is selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, and aryl.
In certain embodiments, the R 6 is selected from C 1-C10 alkyl and C 6-C12 aryl.
In certain embodiments, the R 6 is selected from C 1-C6 alkyl.
In certain embodiments, the R 6 is selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1-ethylpropyl, 1-dimethylpropyl, 1, 2-dimethylpropyl, and 2, 2-dimethylpropyl.
In certain embodiments, the R 5、R6 and the carbon to which it is attached form cycloalkyl, which cycloalkyl is optionally substituted with phenyl;
in certain embodiments, R 1、R6 and the carbon to which it is attached form cycloalkyl, which is optionally substituted with phenyl.
In certain embodiments, the starting aromatic alcohol is selected from the group consisting of
In some embodiments, the reaction process is to put raw materials of aromatic alcohol, catalyst and solvent into a reaction vessel, stir and react the raw materials in an open way, and obtain the product of aromatic ketone compound after post-treatment.
In certain embodiments, the post-treatment step is acid quenching, organic solvent extraction, drying of the organic layer, evaporation of the solvent, and column chromatography purification to obtain the product.
Description of the terms
Unless stated to the contrary, the terms used in the specification and claims have the following meanings.
The term "alkyl" refers to a saturated aliphatic hydrocarbon group which is a straight or branched chain group containing from 1 to 20 carbon atoms, preferably an alkyl group containing from 1 to 12 (e.g., 1,2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12) carbon atoms, more preferably an alkyl group containing from 1 to 6 carbon atoms. Non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1-dimethylpropyl, 1, 2-dimethylpropyl, 2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1-ethyl-2-methylpropyl, 1, 2-trimethylpropyl, 1-dimethylbutyl, 1, 2-dimethylbutyl, 2-dimethylbutyl, 1, 3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2, 3-dimethylbutyl, n-heptyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl 5-methylhexyl, 2, 3-dimethylpentyl, 2, 4-dimethylpentyl, 2-dimethylpentyl, 3-dimethylpentyl, 2-ethylpentyl, 3-ethylpentyl, n-octyl, 2, 3-dimethylhexyl, 2, 4-dimethylhexyl, 2, 5-dimethylhexyl, 2-dimethylhexyl, 3-dimethylhexyl 4, 4-dimethylhexyl, 2-ethylhexyl, 3-ethylhexyl, 4-ethylhexyl, 2-methyl-2-ethylpentyl, 2-methyl-3-ethylpentyl, n-nonyl, 2-methyl-2-ethylhexyl, 2-methyl-3-ethylhexyl, 2-diethylpentyl, n-decyl, 3-diethylhexyl, 2-diethylhexyl, and various branched isomers thereof. More preferred are lower alkyl groups containing 1 to 6 carbon atoms, and non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1-dimethylpropyl, 1, 2-dimethylpropyl, 2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1-ethyl-2-methylpropyl, 1, 2-trimethylpropyl, 1-dimethylbutyl, 1, 2-dimethylbutyl, 2-dimethylbutyl, 1, 3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2, 3-dimethylbutyl, and the like. The alkyl group may be substituted or unsubstituted, and when substituted, it may be substituted at any available point of attachment, and the substituents are preferably independently optionally selected from one or more of D atom, halogen, alkoxy, haloalkyl, haloalkoxy, cycloalkyloxy, heterocyclyloxy, hydroxy, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclyl, aryl and heteroaryl.
The term "alkenyl" refers to an alkyl compound having at least one carbon-carbon double bond in the molecule, wherein alkyl is as defined above. Alkenyl groups may be substituted or unsubstituted, and when substituted, the substituents are preferably one or more substituents independently selected from one or more of alkoxy, halogen, haloalkyl, haloalkoxy, cycloalkyloxy, heterocyclyloxy, hydroxy, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclyl, aryl, and heteroaryl.
The term "alkynyl" refers to an alkyl compound having at least one carbon-carbon triple bond in the molecule, wherein alkyl is as defined above. Alkynyl groups may be substituted or unsubstituted, and when substituted, the substituents are preferably one or more substituents independently selected from one or more of alkoxy, halogen, haloalkyl, haloalkoxy, cycloalkyloxy, heterocyclyloxy, hydroxy, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclyl, aryl and heteroaryl.
The term "cycloalkyl" refers to a saturated or partially unsaturated monocyclic or polycyclic cyclic hydrocarbon substituent, the cycloalkyl ring containing from 3 to 20 carbon atoms, preferably from 3 to 12 carbon atoms, preferably from 3 to 8 (e.g., 3,4,5,6, 7, and 8) carbon atoms, more preferably from 3 to 6 carbon atoms. Non-limiting examples of monocyclic cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptatrienyl, cyclooctyl, and the like; polycyclic cycloalkyl groups include spiro, fused and bridged cycloalkyl groups.
The term "spirocycloalkyl" refers to a 5 to 20 membered, monocyclic, polycyclic group sharing one carbon atom (referred to as the spiro atom) between the monocyclic rings, which may contain one or more double bonds. Preferably 6 to 14 membered, more preferably 7 to 10 membered (e.g. 7, 8, 9 or 10 membered). The spirocycloalkyl group is classified into a single spirocycloalkyl group, a double spirocycloalkyl group or a multiple spirocycloalkyl group according to the number of common spiro atoms between rings, and preferably a single spirocycloalkyl group and a double spirocycloalkyl group. More preferably 3-membered/5-membered, 3-membered/6-membered, 4-membered/4-membered, 4-membered/5-membered, 4-membered/6-membered, 5-membered/5-membered or 5-membered/6-membered, mono-spirocycloalkyl. Non-limiting examples of spirocycloalkyl groups include:
The term "fused ring alkyl" refers to 5 to 20 membered, all carbon polycyclic groups in which each ring in the system shares an adjacent pair of carbon atoms with the other rings in the system, wherein one or more of the rings may contain one or more double bonds. Preferably 6 to 14 membered, more preferably 7 to 10 membered (e.g. 7, 8, 9 or 10 membered). The number of constituent rings may be classified into a bicyclic, tricyclic, tetra-cyclic or polycyclic condensed ring alkyl group, preferably a bicyclic or tricyclic, more preferably a 3-membered/4-membered, 3-membered/5-membered, 3-membered/6-membered, 4-membered/4-membered, 4-membered/5-membered, 4-membered/6-membered, 5-membered/4-membered, 5-membered/5-membered, 5-membered/6-membered, 6-membered/3-membered, 6-membered/4-membered, 6-membered/5-membered and 6-membered/6-membered, and the like. Non-limiting examples of fused ring alkyl groups include:
The term "bridged cycloalkyl" refers to an all-carbon polycyclic group of 5 to 20 members, any two rings sharing two carbon atoms that are not directly attached, which may contain one or more double bonds. Preferably 6 to 14 membered, more preferably 7 to 10 membered (e.g. 7, 8, 9 or 10 membered). Cycloalkyl groups which may be classified as bicyclic, tricyclic, tetracyclic or polycyclic bridged according to the number of constituent rings are preferably bicyclic, tricyclic or tetracyclic, more preferably bicyclic or tricyclic. Non-limiting examples of bridged cycloalkyl groups include:
The cycloalkyl ring includes cycloalkyl (including monocyclic, spiro, fused, and bridged rings) fused to an aryl, heteroaryl, or heterocycloalkyl ring as described above, wherein the ring attached to the parent structure is cycloalkyl, non-limiting examples include Etc.; preference
Cycloalkyl groups may be substituted or unsubstituted, and when substituted, they may be substituted at any available point of attachment, preferably independently optionally selected from one or more of halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, cycloalkyloxy, heterocyclyloxy, hydroxy, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclyl, aryl and heteroaryl.
The term "alkoxy" refers to-O- (alkyl) and-O- (cycloalkyl), wherein alkyl, cycloalkyl are as defined above. Non-limiting examples of alkoxy groups include: methoxy, ethoxy, propoxy and butoxy. Alkoxy groups may be optionally substituted or unsubstituted, and when substituted, are preferably one or more groups independently selected from D atoms, halogen, alkoxy, haloalkyl, haloalkoxy, cycloalkyloxy, heterocyclyloxy, hydroxy, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclyl, aryl, and heteroaryl.
The term "heterocyclyl" refers to a saturated or partially unsaturated monocyclic or polycyclic cyclic substituent comprising 3 to 20 ring atoms, wherein one or more ring atoms are heteroatoms selected from nitrogen, oxygen and sulfur, which sulfur may optionally be oxo (i.e., form sulfoxides or sulfones), but excluding the ring portions of-O-, -O-S-or-S-, the remaining ring atoms being carbon. Preferably from 3 to 12 (e.g., 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12) ring atoms, of which 1 to 4 (e.g., 1,2,3, and 4) are heteroatoms; more preferably 3 to 8 ring atoms (e.g., 3, 4, 5, 6, 7, and 8), of which 1-3 (e.g., 1,2, and 3) are heteroatoms; more preferably 3 to 6 ring atoms, of which 1-3 are heteroatoms; most preferably 5 or 6 ring atoms, of which 1 to 3 are heteroatoms. Non-limiting examples of monocyclic heterocyclyl groups include pyrrolidinyl, tetrahydropyranyl, 1,2,3, 6-tetrahydropyridinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, homopiperazinyl, and the like. Polycyclic heterocyclyl groups include spiro, fused and bridged heterocyclic groups.
The term "spiroheterocyclyl" refers to a5 to 20 membered, polycyclic heterocyclic group having a single ring sharing one atom (referred to as the spiro atom) therebetween, wherein one or more of the ring atoms is a heteroatom selected from nitrogen, oxygen and sulfur, which sulfur may optionally be oxo (i.e., form a sulfoxide or sulfone), the remaining ring atoms being carbon. Which may contain one or more double bonds. Preferably 6 to 14 membered, more preferably 7 to 10 membered (e.g. 7, 8, 9 or 10 membered). The spiroheterocyclyl groups are classified into a single spiroheterocyclyl group, a double spiroheterocyclyl group or a multiple spiroheterocyclyl group according to the number of common spiro atoms between rings, and preferably a single spiroheterocyclyl group and a double spiroheterocyclyl group. More preferably 3-membered/5-membered, 3-membered/6-membered, 4-membered/4-membered, 4-membered/5-membered, 4-membered/6-membered, 5-membered/5-membered or 5-membered/6-membered single spiro heterocyclyl. Non-limiting examples of spiroheterocyclyl groups include:
The term "fused heterocyclyl" refers to a 5 to 20 membered, polycyclic heterocyclic group in which each ring in the system shares an adjacent pair of atoms with the other rings in the system, one or more of which may contain one or more double bonds, wherein one or more ring atoms are heteroatoms selected from nitrogen, oxygen and sulfur, which may optionally be oxo (i.e., form sulfoxides or sulfones), and the remaining ring atoms are carbon. Preferably 6 to 14 membered, more preferably 7 to 10 membered (e.g. 7, 8, 9 or 10 membered). The number of constituent rings may be classified into a bicyclic, tricyclic, tetracyclic or polycyclic fused heterocyclic group, preferably a bicyclic or tricyclic, more preferably a 3-membered/4-membered, 3-membered/5-membered, 3-membered/6-membered, 4-membered/4-membered, 4-membered/5-membered, 4-membered/6-membered, 5-membered/4-membered, 5-membered/5-membered, 5-membered/6-membered, 6-membered/3-membered, 6-membered/4-membered, 6-membered/5-membered and 6-membered bicyclic fused heterocyclic group. Non-limiting examples of fused heterocyclyl groups include:
The term "bridged heterocyclyl" refers to a 5 to 14 membered, polycyclic heterocyclic group in which any two rings share two atoms which are not directly connected, which may contain one or more double bonds, wherein one or more of the ring atoms is a heteroatom selected from nitrogen, oxygen and sulfur, which may optionally be oxo (i.e., form sulfoxides or sulfones), the remaining ring atoms being carbon. Preferably 6 to 14 membered, more preferably 7 to 10 membered (e.g. 7, 8, 9 or 10 membered). Heterocyclic groups which may be classified as bicyclic, tricyclic, tetracyclic or polycyclic bridged according to the number of constituent rings are preferably bicyclic, tricyclic or tetracyclic, more preferably bicyclic or tricyclic. Non-limiting examples of bridged heterocyclyl groups include:
The heterocyclyl ring includes heterocyclyl (including monocyclic, spiro, fused and bridged heterocyclic rings) as described above fused to an aryl, heteroaryl or cycloalkyl ring, wherein the ring attached to the parent structure is heterocyclyl, non-limiting examples of which include:
Etc.
The heterocyclic group may be substituted or unsubstituted, and when substituted, it may be substituted at any available point of attachment, preferably independently optionally selected from one or more of halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, cycloalkyloxy, heterocyclyloxy, hydroxy, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclyl, aryl and heteroaryl.
The term "aryl" refers to a 6 to 14 membered all-carbon monocyclic or fused polycyclic (fused polycyclic being a ring sharing adjacent pairs of carbon atoms) group having a conjugated pi-electron system, preferably 6 to 10 membered, such as phenyl and naphthyl. The aryl ring includes aryl rings fused to heteroaryl, heterocyclyl, or cycloalkyl rings as described above, wherein the ring attached to the parent structure is an aryl ring, non-limiting examples of which include:
Aryl groups may be substituted or unsubstituted, and when substituted, they may be substituted at any available point of attachment, preferably independently optionally selected from one or more of halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, cycloalkyloxy, heterocyclyloxy, hydroxy, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclyl, aryl and heteroaryl.
The term "heteroaryl" refers to a heteroaromatic system containing 1 to 4 (e.g., 1, 2, 3, and 4) heteroatoms, 5 to 14 ring atoms, wherein the heteroatoms are selected from oxygen, sulfur, and nitrogen. Heteroaryl is preferably 5 to 10 membered (e.g., 5, 6, 7, 8, 9, or 10 membered), more preferably 5 or 6 membered, such as furyl, thienyl, pyridyl, pyrrolyl, N-alkylpyrrolyl, pyrimidinyl, pyrazinyl, pyridazinyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, and the like. The heteroaryl ring includes heteroaryl condensed onto an aryl, heterocyclyl, or cycloalkyl ring as described above, wherein the ring attached to the parent structure is a heteroaryl ring, non-limiting examples of which include:
Heteroaryl groups may be substituted or unsubstituted, and when substituted, they may be substituted at any available point of attachment, preferably independently optionally selected from one or more of halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, cycloalkyloxy, heterocyclyloxy, hydroxy, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclyl, aryl and heteroaryl.
The cycloalkyl, heterocyclyl, aryl and heteroaryl groups mentioned above include residues derived from the removal of one hydrogen atom from the parent ring atom, or residues derived from the removal of two hydrogen atoms from the same or two different ring atoms of the parent, i.e. "divalent cycloalkyl", "divalent heterocyclyl", "arylene", "heteroarylene".
The term "hydroxyalkyl" refers to an alkyl group substituted with one or more hydroxyl groups, wherein alkyl is as defined above.
The term "halogen" refers to fluorine, chlorine, bromine or iodine.
The term "hydroxy" refers to-OH.
The term "mercapto" refers to-SH.
The term "amino" refers to-NH 2.
The term "cyano" refers to-CN.
The term "nitro" refers to-NO 2.
The term "oxo" or "oxo" refers to "=o".
The term "carboxy" refers to-C (O) OH.
"Optional" or "optionally" means that the subsequently described event or circumstance may but need not occur, and that the description includes instances where the event or circumstance occurs or does not. For example, "a heterocyclic group optionally substituted with an alkyl group" means that an alkyl group may be, but is not necessarily, present, and the description includes cases where the heterocyclic group is substituted with an alkyl group and cases where the heterocyclic group is not substituted with an alkyl group.
"Substituted" means that one or more hydrogen atoms, preferably 1 to 5, more preferably 1 to 3, in the group are independently substituted with a corresponding number of substituents. The person skilled in the art is able to determine (by experiment or theory) possible or impossible substitutions without undue effort. For example, amino or hydroxyl groups having free hydrogen may be unstable when bound to carbon atoms having unsaturated (e.g., olefinic) bonds.
The process of the present invention is illustrated by the following specific examples, it being understood that these examples are illustrative of the basic principles, main features and advantages of the present invention, and the present invention is not limited by the scope of the following examples; the implementation conditions employed in the examples may be further adjusted according to specific requirements, and the implementation conditions not specified are generally those in routine experiments.
The 1 H NMR spectra in the examples below were determined using a Bruker instrument (400 MHz) and the chemical shifts were expressed in ppm. Tetramethylsilane internal standard (0.00 ppm) was used. 1 H NMR representation method: s=singlet, d=doublet, t=triplet, q=quartet, m=multiplet, br=broadened, dd=doublet of doublet, dt=doublet of triplet. If coupling constants are provided, they are in Hz.
The mass spectrum is measured by an LC/MS instrument, and the ionization mode is ESI.
High performance liquid chromatograph model: agilent 1260, siemens flying U3000; chromatographic column model: waters xbrige C18 < 18 > (4.6X105 mm,3.5 μm); mobile phase: ACN, B Water (0.1% H 3PO4); flow rate: 1.0mL/min; gradient ：5％A for 1min,increase to 20％A within 4min,increase to 80％A within 8min,80％A for 2min,back to 5％A within 0.1min; wavelength: 220nm; column incubator: 35 ℃.
TLC: thin layer chromatography. The thin layer chromatography silica gel plate is a smoke table yellow sea HSGF254 or Qingdao GF254 silica gel plate, the specification of the silica gel plate used by the Thin Layer Chromatography (TLC) is 0.2mm-0.3mm, and the specification of the thin layer chromatography separation and purification product is 0.4mm-0.5mm.
Column chromatography generally uses tobacco stage yellow sea silica gel 200-300 mesh silica gel as carrier.
In the following examples, unless otherwise indicated, all temperatures are in degrees celsius and unless otherwise indicated, various starting materials and reagents are either commercially available or synthesized according to known methods, and are used without further purification, and unless otherwise indicated, commercially available manufacturers include, but are not limited to, the national pharmaceutical community, the carbofuran technologies, the tencel (Shanghai) chemical industry development limited, the Shanghai Pico pharmaceutical technologies limited, the Shanghai Michelson chemical technologies limited, and the like.
The examples are not particularly described, and the solution in the reaction is an aqueous solution.
The examples are not specifically described, and the reaction temperature is room temperature and is 20℃to 30 ℃.
The monitoring of the progress of the reaction in the examples employed Thin Layer Chromatography (TLC), the developing reagent used for the reaction, the system of eluent for column chromatography employed for purifying the compound or the developing reagent system of thin layer chromatography included: a: petroleum ether and ethyl acetate systems; b: methylene chloride and methanol systems; c: n-hexane: ethyl acetate; the volume ratio of the solvent is different according to the polarity of the compound, and can be adjusted by adding a small amount of acidic or alkaline reagent, such as acetic acid or triethylamine.
Example 1
97.7Mg (0.8 mmol) of 1-phenethyl alcohol, 192.2mg (2 mmol) of sodium tert-butoxide are accurately weighed, placed in a 25mL reaction bottle, 3mL of toluene is added, the stirring rate is 800rmp, the reaction is carried out at room temperature for 30min, after the reaction is finished, 3mL of 2mol/L HCl aqueous solution is added for quenching, ethyl acetate is added for extraction (5 mL of 3 times), the organic phases are combined, anhydrous sodium sulfate is dried, the filtrate is filtered, the solvent is distilled off, and the residue is subjected to petroleum ether-ethyl acetate (10:1) column chromatography to obtain 90.1mg (yield: 93%) of acetophenone.
Example 2
Accurately weighing 121.7mg (0.8 mmol) of 1- (4-methoxyphenyl) ethanol, 192.2mg (2 mmol) of sodium tert-butoxide, placing into a 25mL reaction bottle, adding 3mL of toluene, stirring at a rate of 800rmp, performing open reaction at room temperature for 30min, after the reaction is finished, adding 3mL of 2mol/L HCl aqueous solution for quenching, adding ethyl acetate for extraction (5 mL for 3 times), merging organic phases, drying over anhydrous sodium sulfate, filtering, evaporating the solvent from the filtrate, and performing petroleum ether-ethyl acetate (10:1) column chromatography on the residue to obtain 121.05mg (yield: 99%) of 4-methoxyacetophenone.
Example 3
142.6Mg (0.8 mmol) of 2-methyl-1-phenyl-1-pentanol, 192.2mg (2 mmol) of sodium tert-butoxide are accurately weighed, placed in a 25mL reaction flask, 3mL of toluene are added, the stirring rate is 800rmp, the reaction is carried out for 30min at room temperature, after the reaction is finished, 3mL of 2mol/L HCl aqueous solution is added for quenching, ethyl acetate is added for extraction (5 mL for 3 times), the organic phases are combined, anhydrous sodium sulfate is dried, filtration is carried out, the filtrate is distilled to remove the solvent, and the residue is subjected to petroleum ether-ethyl acetate (10:1) column chromatography to obtain 134.1mg (yield: 94%) of 2-methyl-1-phenylpentan-1-one.
Example 4
Accurately weighing 145.8mg (0.8 mmol) of 9-fluorenol, 192.2mg (2 mmol) of sodium tert-butoxide, placing in a 25mL reaction bottle, adding 3mL of toluene, stirring at a rate of 800rmp, reacting at room temperature for 30min with an open mouth, adding 3mL of 2mol/L of HCl aqueous solution for quenching after the reaction is finished, adding ethyl acetate for extraction (5 mL of 3 times), combining organic phases, drying over anhydrous sodium sulfate, filtering, evaporating the filtrate to remove the solvent, and subjecting the residue to petroleum ether-ethyl acetate (10:1) column chromatography to obtain 135.6mg (yield: 93%) of 9-fluorenone.
Example 5
Accurately weighing 121.7mg (0.8 mmol) of 1- (4-methoxyphenyl) ethanol, 224.4mg (2 mmol) of potassium tert-butoxide, placing into a 25mL reaction bottle, adding 3mL of toluene, stirring at a rate of 800rmp, performing open reaction at room temperature for 30min, after the reaction is finished, adding 3mL of 2mol/L HCl aqueous solution for quenching, adding ethyl acetate for extraction (5 mL for 3 times), merging organic phases, drying over anhydrous sodium sulfate, filtering, evaporating the solvent from the filtrate, and performing petroleum ether-ethyl acetate (10:1) column chromatography on the residue to obtain 110.7mg (yield: 91%) of 4-methoxyacetophenone.
Example 6
Accurately weighing 121.7mg (0.8 mmol) of 1- (4-methoxyphenyl) ethanol, 192.2mg (2 mmol) of sodium tert-butoxide, placing into a 25mL reaction bottle, adding 3mL of chlorobenzene, stirring at a rate of 800rmp, performing open reaction at room temperature for 30min, after the reaction is finished, adding 3mL of 2mol/L HCl aqueous solution for quenching, adding ethyl acetate for extraction (5 mL for 3 times), merging organic phases, drying over anhydrous sodium sulfate, filtering, evaporating the solvent from the filtrate, and performing petroleum ether-ethyl acetate (10:1) column chromatography on the residue to obtain 101.1mg (yield: 83%) of 4-methoxyacetophenone.
Example 7
Accurately weighing 121.7mg (0.8 mmol) of 1- (4-methoxyphenyl) ethanol, 192.2mg (2 mmol) of sodium tert-butoxide, placing into a 25mL reaction bottle, adding 3mL of toluene, stirring at a rate of 800rmp, performing open reaction at room temperature for 12h, after the reaction is finished, adding 3mL of 2mol/L HCl aqueous solution for quenching, adding ethyl acetate for extraction (5 mL for 3 times), merging organic phases, drying over anhydrous sodium sulfate, filtering, evaporating the solvent from the filtrate, and performing petroleum ether-ethyl acetate (10:1) column chromatography on the residue to obtain 118.1mg (yield: 97%) of 4-methoxyacetophenone.
It should be understood that the above examples are illustrative and are not intended to encompass all possible implementations encompassed by the claims. Various modifications and changes may be made in the above embodiments without departing from the scope of the disclosure. Likewise, the various features of the above embodiments may also be combined arbitrarily to form further embodiments of the disclosure that may not be explicitly described. Thus, the above examples merely represent several embodiments of the present disclosure, and do not limit the scope of protection of the present disclosure.
Claims (20)
1. A process for preparing aromatic ketone compound features that the aromatic alcohol as raw material is reacted in the presence of catalyst and oxidant to obtain aromatic ketone compound,
The catalyst is an organic base, and the catalyst is an organic base,
The oxidant is air or oxygen;
The reaction process is as follows:
Wherein A 1 is selected from C-R 1;
A 2 is selected from C-R 2;
a 3 is selected from C-R 3;
A 4 is selected from C-R 4;
a 5 is selected from C-R 5;
R 1、R2、R3、R4、R5 is each independently selected from the group consisting of hydrogen, halogen, alkyl, alkoxy, alkenyl, alkynyl, cyano, hydroxy, nitro, oxo, cycloalkyl, aryl, and heteroaryl, wherein the alkyl, alkoxy, cycloalkyl, aryl, or heteroaryl is optionally substituted with one or more substituents selected from the group consisting of halogen, alkyl, alkoxy, cyano, amino, nitro, hydroxy, hydroxyalkyl, carboxyl, cycloalkyl, aryl, and heteroaryl;
r 6 is selected from the group consisting of alkyl, cycloalkyl, aryl, and heteroaryl, wherein said alkyl, cycloalkyl, aryl, or heteroaryl is optionally substituted with one or more substituents selected from the group consisting of halogen, alkyl, alkoxy, cyano, amino, nitro, hydroxy, hydroxyalkyl, carboxyl, cycloalkyl, aryl, and heteroaryl;
or R 5、R6 and the carbon to which it is attached form cycloalkyl, heterocyclyl, wherein said cycloalkyl, heterocyclyl is optionally substituted with one or more substituents selected from the group consisting of halogen, alkyl, alkoxy, cyano, amino, nitro, hydroxy, hydroxyalkyl, carboxyl, cycloalkyl, aryl and heteroaryl;
Or R 1、R6 and the carbon to which it is attached form cycloalkyl, heterocyclyl, wherein said cycloalkyl, heterocyclyl is optionally substituted with one or more substituents selected from the group consisting of halogen, alkyl, alkoxy, cyano, amino, nitro, hydroxy, hydroxyalkyl, carboxyl, cycloalkyl, aryl and heteroaryl;
Wherein the reaction is carried out in a solvent, and the solvent is one or two of toluene, ethylbenzene, mesitylene, chlorobenzene, dichloromethane and chloroform.
2. The method of claim 1, wherein the organic base is selected from one or more of lithium t-butoxide, sodium t-butoxide, potassium t-butoxide, sodium ethoxide, potassium ethoxide, and lithium ethoxide.
3. The method of claim 1, wherein the organic base is one or more of lithium t-butoxide, sodium t-butoxide, and potassium t-butoxide.
4. The method of claim 1, wherein the organic base is sodium t-butoxide.
5. The method of claim 1, wherein the solvent is toluene.
6. The method of claim 1, wherein the reaction temperature is from 0 ℃ to 50 ℃.
7. The method of claim 1, wherein the reaction temperature is room temperature.
8. The method of claim 1, wherein the molar ratio of the starting aromatic alcohol to the organic base is from 1:0.5 to 5.
9. The method of claim 1, wherein the molar ratio of the starting aromatic alcohol to the organic base is 1:2.5.
10. The method of any one of claims 1-9, wherein each R 1、R2、R3、R4、R5 is independently selected from the group consisting of hydrogen, halogen, alkyl, alkoxy, cycloalkyl, aryl, and heteroaryl.
11. The method of any one of claims 1-9, wherein each R 1、R2、R3、R4、R5 is independently selected from the group consisting of hydrogen, alkyl, alkoxy, and aryl.
12. The method of any one of claims 1-9, wherein each R 1、R2、R3、R4、R5 is independently selected from the group consisting of hydrogen, C 1-C10 alkyl, C 1-C10 alkoxy, and C 6-C12 aryl.
13. The method of any one of claims 1-9, wherein R 6 is selected from the group consisting of alkyl, cycloalkyl, and aryl.
14. The method of any one of claims 1-9, wherein R 6 is selected from the group consisting of C 1-C10 alkyl and C 6-C12 aryl.
15. The method of any one of claims 1-9, wherein R 6 is selected from C 1-C6 alkyl.
16. The method of any one of claims 1-9, wherein R 5、R6 and the carbon to which it is attached form cycloalkyl, optionally substituted with phenyl.
17. The method of any one of claims 1-9, wherein R 1、R6 and the carbon to which it is attached form cycloalkyl, optionally substituted with phenyl.
18. The method of any one of claims 1-9, wherein the starting aromatic alcohol is selected from the group consisting of
19. The method according to any one of claims 1 to 9, wherein the reaction process is to put raw materials of aromatic alcohol, catalyst and solvent into a reaction vessel, stir and react the raw materials in an open way, and obtain the product of aromatic ketone compound after post-treatment.
20. The method of claim 19, wherein the post-treatment step is performed by adding acid quenching after the reaction is completed, extracting with an organic solvent, evaporating the solvent, and purifying by column chromatography to obtain the product.
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