CN115197108A - Preparation method of gamma-ketosulfone compound - Google Patents
Preparation method of gamma-ketosulfone compound Download PDFInfo
- Publication number
- CN115197108A CN115197108A CN202210830894.1A CN202210830894A CN115197108A CN 115197108 A CN115197108 A CN 115197108A CN 202210830894 A CN202210830894 A CN 202210830894A CN 115197108 A CN115197108 A CN 115197108A
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- China
- Prior art keywords
- acid
- compound
- chain alkyl
- formula
- phenyl
- Prior art date
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- Granted
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 65
- 238000006243 chemical reaction Methods 0.000 claims abstract description 34
- 150000001875 compounds Chemical class 0.000 claims abstract description 30
- 239000002253 acid Substances 0.000 claims abstract description 22
- 239000002904 solvent Substances 0.000 claims abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 17
- 238000002156 mixing Methods 0.000 claims abstract description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 306
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 149
- 239000000047 product Substances 0.000 claims description 118
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 102
- 238000005406 washing Methods 0.000 claims description 102
- 239000000741 silica gel Substances 0.000 claims description 100
- 229910002027 silica gel Inorganic materials 0.000 claims description 100
- -1 C3-C10 cyclic alkyl Chemical group 0.000 claims description 89
- XRHGYUZYPHTUJZ-UHFFFAOYSA-N 4-chlorobenzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1 XRHGYUZYPHTUJZ-UHFFFAOYSA-N 0.000 claims description 54
- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 claims description 54
- 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 54
- 238000001914 filtration Methods 0.000 claims description 53
- 125000000217 alkyl group Chemical group 0.000 claims description 52
- 239000000706 filtrate Substances 0.000 claims description 51
- 239000007788 liquid Substances 0.000 claims description 51
- 239000003208 petroleum Substances 0.000 claims description 51
- 238000013375 chromatographic separation Methods 0.000 claims description 43
- 125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 31
- 125000000623 heterocyclic group Chemical group 0.000 claims description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims description 21
- 239000001257 hydrogen Substances 0.000 claims description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 16
- 150000002431 hydrogen Chemical class 0.000 claims description 16
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 150000002367 halogens Chemical class 0.000 claims description 15
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims description 14
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical group CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 12
- URLKBWYHVLBVBO-UHFFFAOYSA-N Para-Xylene Chemical group CC1=CC=C(C)C=C1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 12
- IVSZLXZYQVIEFR-UHFFFAOYSA-N m-xylene Chemical group CC1=CC=CC(C)=C1 IVSZLXZYQVIEFR-UHFFFAOYSA-N 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 239000001301 oxygen Substances 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 12
- 125000004434 sulfur atom Chemical group 0.000 claims description 12
- 125000006736 (C6-C20) aryl group Chemical group 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 claims description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 8
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical class C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 8
- LPNBBFKOUUSUDB-UHFFFAOYSA-N p-toluic acid Chemical compound CC1=CC=C(C(O)=O)C=C1 LPNBBFKOUUSUDB-UHFFFAOYSA-N 0.000 claims description 8
- 229940078552 o-xylene Drugs 0.000 claims description 6
- OTLNPYWUJOZPPA-UHFFFAOYSA-N 4-nitrobenzoic acid Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)C=C1 OTLNPYWUJOZPPA-UHFFFAOYSA-N 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 239000004305 biphenyl Chemical class 0.000 claims description 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 4
- XRXMNWGCKISMOH-UHFFFAOYSA-N 2-bromobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1Br XRXMNWGCKISMOH-UHFFFAOYSA-N 0.000 claims description 4
- UOBYKYZJUGYBDK-UHFFFAOYSA-N 2-naphthoic acid Chemical compound C1=CC=CC2=CC(C(=O)O)=CC=C21 UOBYKYZJUGYBDK-UHFFFAOYSA-N 0.000 claims description 4
- SLAMLWHELXOEJZ-UHFFFAOYSA-N 2-nitrobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1[N+]([O-])=O SLAMLWHELXOEJZ-UHFFFAOYSA-N 0.000 claims description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 4
- QBHDSQZASIBAAI-UHFFFAOYSA-N 4-acetylbenzoic acid Chemical compound CC(=O)C1=CC=C(C(O)=O)C=C1 QBHDSQZASIBAAI-UHFFFAOYSA-N 0.000 claims description 4
- BBYDXOIZLAWGSL-UHFFFAOYSA-N 4-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C=C1 BBYDXOIZLAWGSL-UHFFFAOYSA-N 0.000 claims description 4
- 239000005711 Benzoic acid Substances 0.000 claims description 4
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 4
- 235000010233 benzoic acid Nutrition 0.000 claims description 4
- 235000010290 biphenyl Nutrition 0.000 claims description 4
- 235000019253 formic acid Nutrition 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 229910017604 nitric acid Inorganic materials 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- UQRONKZLYKUEMO-UHFFFAOYSA-N 4-methyl-1-(2,4,6-trimethylphenyl)pent-4-en-2-one Chemical group CC(=C)CC(=O)Cc1c(C)cc(C)cc1C UQRONKZLYKUEMO-UHFFFAOYSA-N 0.000 claims description 2
- 125000002178 anthracenyl group Chemical class C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 claims description 2
- 125000001797 benzyl group Chemical class [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000002603 chloroethyl group Chemical class [H]C([*])([H])C([H])([H])Cl 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical class 0.000 claims description 2
- 125000001041 indolyl group Chemical class 0.000 claims description 2
- 125000000468 ketone group Chemical group 0.000 claims description 2
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 2
- 125000001624 naphthyl group Chemical class 0.000 claims description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 8
- 229910052751 metal Inorganic materials 0.000 abstract description 7
- 239000002184 metal Substances 0.000 abstract description 7
- 238000001308 synthesis method Methods 0.000 abstract description 7
- 230000015572 biosynthetic process Effects 0.000 abstract description 6
- 239000000126 substance Substances 0.000 abstract description 6
- 239000000463 material Substances 0.000 abstract description 5
- 239000007800 oxidant agent Substances 0.000 abstract description 5
- 150000002978 peroxides Chemical class 0.000 abstract description 5
- 239000003054 catalyst Substances 0.000 abstract description 4
- 230000001590 oxidative effect Effects 0.000 abstract description 4
- 230000004071 biological effect Effects 0.000 abstract description 3
- 230000007547 defect Effects 0.000 abstract description 3
- 239000012634 fragment Substances 0.000 abstract description 3
- 238000007040 multi-step synthesis reaction Methods 0.000 abstract description 3
- 230000000144 pharmacologic effect Effects 0.000 abstract description 3
- 150000002894 organic compounds Chemical class 0.000 abstract description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 106
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 94
- 238000004440 column chromatography Methods 0.000 description 59
- 239000007787 solid Substances 0.000 description 53
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 47
- CHLCPTJLUJHDBO-UHFFFAOYSA-M sodium;benzenesulfinate Chemical group [Na+].[O-]S(=O)C1=CC=CC=C1 CHLCPTJLUJHDBO-UHFFFAOYSA-M 0.000 description 30
- JITPLZPWKYUTDM-UHFFFAOYSA-N 1-phenylprop-2-yn-1-one Chemical compound C#CC(=O)C1=CC=CC=C1 JITPLZPWKYUTDM-UHFFFAOYSA-N 0.000 description 20
- 239000000203 mixture Substances 0.000 description 17
- 238000000926 separation method Methods 0.000 description 15
- 238000007789 sealing Methods 0.000 description 13
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 150000001336 alkenes Chemical class 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 4
- 230000002194 synthesizing effect Effects 0.000 description 4
- RVCKCEDKBVEEHL-UHFFFAOYSA-N 2,3,4,5,6-pentachlorobenzyl alcohol Chemical compound OCC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl RVCKCEDKBVEEHL-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 3
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 238000004007 reversed phase HPLC Methods 0.000 description 3
- 229940077386 sodium benzenesulfonate Drugs 0.000 description 3
- MZSDGDXXBZSFTG-UHFFFAOYSA-M sodium;benzenesulfonate Chemical compound [Na+].[O-]S(=O)(=O)C1=CC=CC=C1 MZSDGDXXBZSFTG-UHFFFAOYSA-M 0.000 description 3
- 238000004611 spectroscopical analysis Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 3
- KLTVSWGXIAYTHO-UHFFFAOYSA-N 1-Octen-3-one Chemical compound CCCCCC(=O)C=C KLTVSWGXIAYTHO-UHFFFAOYSA-N 0.000 description 2
- MQJKPEGWNLWLTK-UHFFFAOYSA-N Dapsone Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=C1 MQJKPEGWNLWLTK-UHFFFAOYSA-N 0.000 description 2
- SUJUHGSWHZTSEU-UHFFFAOYSA-N Tipranavir Natural products C1C(O)=C(C(CC)C=2C=C(NS(=O)(=O)C=3N=CC(=CC=3)C(F)(F)F)C=CC=2)C(=O)OC1(CCC)CCC1=CC=CC=C1 SUJUHGSWHZTSEU-UHFFFAOYSA-N 0.000 description 2
- NTJOBXMMWNYJFB-UHFFFAOYSA-N amisulpride Chemical compound CCN1CCCC1CNC(=O)C1=CC(S(=O)(=O)CC)=C(N)C=C1OC NTJOBXMMWNYJFB-UHFFFAOYSA-N 0.000 description 2
- 229960003036 amisulpride Drugs 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 229960000860 dapsone Drugs 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- KFZUDNZQQCWGKF-UHFFFAOYSA-M sodium;4-methylbenzenesulfinate Chemical compound [Na+].CC1=CC=C(S([O-])=O)C=C1 KFZUDNZQQCWGKF-UHFFFAOYSA-M 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 150000003457 sulfones Chemical group 0.000 description 2
- NZPXPXAGXYTROM-FYBSXPHGSA-N tipranavir Chemical compound C([C@@]1(CCC)OC(O)=C([C@H](CC)C=2C=C(NS(=O)(=O)C=3N=CC(=CC=3)C(F)(F)F)C=CC=2)C(=O)C1)CC1=CC=CC=C1 NZPXPXAGXYTROM-FYBSXPHGSA-N 0.000 description 2
- 229960000838 tipranavir Drugs 0.000 description 2
- BPQMGSKTAYIVFO-UHFFFAOYSA-N vismodegib Chemical compound ClC1=CC(S(=O)(=O)C)=CC=C1C(=O)NC1=CC=C(Cl)C(C=2N=CC=CC=2)=C1 BPQMGSKTAYIVFO-UHFFFAOYSA-N 0.000 description 2
- 229960004449 vismodegib Drugs 0.000 description 2
- ACUGGDVMDPMOFH-UHFFFAOYSA-N 1-(4-fluorophenyl)prop-2-yn-1-one Chemical compound FC1=CC=C(C(=O)C#C)C=C1 ACUGGDVMDPMOFH-UHFFFAOYSA-N 0.000 description 1
- WUZGMAXWGIRPRC-UHFFFAOYSA-N 1-phenylbut-3-yn-2-one Chemical compound C#CC(=O)CC1=CC=CC=C1 WUZGMAXWGIRPRC-UHFFFAOYSA-N 0.000 description 1
- DMAMKPWVVZCTDR-UHFFFAOYSA-N 3-(benzenesulfonyl)-1-(4-fluorophenyl)propan-1-one Chemical compound C1=CC(F)=CC=C1C(=O)CCS(=O)(=O)C1=CC=CC=C1 DMAMKPWVVZCTDR-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 229930193822 Adociaquinone Natural products 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000036436 anti-hiv Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- MNJVRJDLRVPLFE-UHFFFAOYSA-N etoricoxib Chemical compound C1=NC(C)=CC=C1C1=NC=C(Cl)C=C1C1=CC=C(S(C)(=O)=O)C=C1 MNJVRJDLRVPLFE-UHFFFAOYSA-N 0.000 description 1
- 229960004945 etoricoxib Drugs 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 125000001736 nosyl group Chemical group S(=O)(=O)(C1=CC=C([N+](=O)[O-])C=C1)* 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 208000020352 skin basal cell carcinoma Diseases 0.000 description 1
- HSMQEPRQVNOYDB-UHFFFAOYSA-N sodium;2,4,6-trimethylbenzenesulfinic acid Chemical compound [Na].CC1=CC(C)=C(S(O)=O)C(C)=C1 HSMQEPRQVNOYDB-UHFFFAOYSA-N 0.000 description 1
- MZXNLGKKMURPNV-UHFFFAOYSA-M sodium;2-chloroethanesulfinate Chemical compound [Na+].[O-]S(=O)CCCl MZXNLGKKMURPNV-UHFFFAOYSA-M 0.000 description 1
- JJLZHSLAFQPNON-UHFFFAOYSA-M sodium;4-(trifluoromethoxy)benzenesulfinate Chemical compound [Na+].[O-]S(=O)C1=CC=C(OC(F)(F)F)C=C1 JJLZHSLAFQPNON-UHFFFAOYSA-M 0.000 description 1
- IRJVONHUBTUTAL-UHFFFAOYSA-M sodium;4-(trifluoromethyl)benzenesulfinate Chemical compound [Na+].[O-]S(=O)C1=CC=C(C(F)(F)F)C=C1 IRJVONHUBTUTAL-UHFFFAOYSA-M 0.000 description 1
- UHTHXINUPNECBQ-UHFFFAOYSA-M sodium;4-bromobenzenesulfonate Chemical compound [Na+].[O-]S(=O)(=O)C1=CC=C(Br)C=C1 UHTHXINUPNECBQ-UHFFFAOYSA-M 0.000 description 1
- ZBKKIKXRUXGSDO-UHFFFAOYSA-M sodium;4-fluorobenzenesulfonate Chemical compound [Na+].[O-]S(=O)(=O)C1=CC=C(F)C=C1 ZBKKIKXRUXGSDO-UHFFFAOYSA-M 0.000 description 1
- IILVFSMKWWTVRT-UHFFFAOYSA-M sodium;4-iodobenzenesulfinate Chemical compound [Na+].[O-]S(=O)C1=CC=C(I)C=C1 IILVFSMKWWTVRT-UHFFFAOYSA-M 0.000 description 1
- JZEDOEPVMYKFAB-UHFFFAOYSA-M sodium;4-methoxybenzenesulfinate Chemical compound [Na+].COC1=CC=C(S([O-])=O)C=C1 JZEDOEPVMYKFAB-UHFFFAOYSA-M 0.000 description 1
- YAHKQSVGVMFKMR-UHFFFAOYSA-M sodium;4-nitrobenzenesulfinate Chemical compound [Na+].[O-][N+](=O)C1=CC=C(S([O-])=O)C=C1 YAHKQSVGVMFKMR-UHFFFAOYSA-M 0.000 description 1
- CQSFZPDGBPHCHV-UHFFFAOYSA-M sodium;cyclopropanesulfinate Chemical compound [Na+].[O-]S(=O)C1CC1 CQSFZPDGBPHCHV-UHFFFAOYSA-M 0.000 description 1
- JGGFVSGYTHUAOQ-UHFFFAOYSA-M sodium;naphthalene-2-sulfinate Chemical compound [Na+].C1=CC=CC2=CC(S(=O)[O-])=CC=C21 JGGFVSGYTHUAOQ-UHFFFAOYSA-M 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
- C07C315/04—Preparation of sulfones; Preparation of sulfoxides by reactions not involving the formation of sulfone or sulfoxide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
- C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/12—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
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Abstract
The invention relates to the technical field of synthesis of organic compounds, in particular to a preparation method of a gamma-ketosulfone compound, which comprises the following steps: mixing an alkynone compound with a structure shown in a formula I, a compound with a structure shown in a formula II, an acid and a solvent, and reacting to obtain a gamma-ketosulfone compound with a structure shown in a formula III; the invention overcomes the defects that the existing synthesis method of the gamma-ketosulfone compound has complex synthesis steps, can be completed by adopting a multi-step synthesis process, and also needs to use a metal catalyst, a chemical equivalent oxidant or peroxide and the like; the atom economy is kept to the utmost extent; the compound has stable molecular structure and excellent chemical property, and the molecular cut block and the compound fragment contain rich contents of biological activity and pharmacological activity; the method also has the characteristics of simple reaction system, mild reaction conditions, fewer steps, fewer reaction devices, simple and convenient experimental operation, wide material sources, low price, easy obtainment and the like.
Description
Technical Field
The invention relates to the technical field of synthesis of organic compounds, in particular to a preparation method of a gamma-ketosulfone compound.
Background
The sulfone compounds are common organic intermediates, and play a vital role in the fields of medicines, organic pesticides, novel functional materials and the like. Sulfone functional groups are also an important class of small molecular structures of drugs, such as adroquinone (Adociaquinones) for the treatment of breast cancer, dapsone (Dapsone), the antibacterial agent Vismodegib (Vismodegib) for the treatment of basal cell carcinoma of the skin, the anti-HIV drug Tipranavir (Tipranavir), amisulpride (Amisulpride) for the treatment of schizophrenia, and etaxib (Etoricoxib) for the treatment of osteoarthritis, all containing sulfone structural units. Wherein, part of the ketone sulfone derivatives have bactericidal activity and are hopeful to be drugs for resisting melanoma. Because the ketone sulfone derivatives have important potential application value, the synthesis of the compounds has very important significance. Although some documents report the synthesis methods of the compounds, the further development of the synthesis methods is still a hot spot in the field of organic synthesis.
In the field of organic synthesis, the synthesis method of the gamma-ketosulfone derivative mainly comprises the following steps: 1) Nucleophilic substitution with sodium benzene sulfinate and 2-chloroketene (j.chem.soc. (C), 1969,0,1204-1208); 2) Elimination reactions using bromine-substituted saturated ketone sulfones (J.am. Chem. Soc.1935,57, 1448-1452); 3) By oxidation of the corresponding thioether or sulfoxide compound (J.Am. Chem. Soc.1935,57, 1316-1321); 4) By addition reaction of sulfonyl radicals with alkenes or alkynes (Green chem.2014,16,2988-2991, chem.Sci.2015,6,6654-6658, chem.AsianJ.2016,11, 3334-3338). However, most of these methods require metal catalysis, or the addition of large amounts of metal oxidants or peroxides; the reaction conditions are harsh, the steps are long, and the application limit of the synthesis method of the gamma-ketosulfone derivative is undoubtedly greatly limited, especially in the pharmaceutical industry. Therefore, a high-efficiency, simple, convenient and environment-friendly synthetic method for synthesizing the gamma-ketosulfone derivative under mild conditions without metal catalysis needs to be developed.
Disclosure of Invention
In view of the above, the technical problem to be solved by the present invention is to provide a method for preparing a γ -ketosulfone compound, which is simple to operate and does not need metal catalysis.
The invention provides a preparation method of a gamma-ketosulfone compound, which comprises the following steps:
mixing an alkynone compound with a structure shown in a formula I, a compound with a structure shown in a formula II, an acid and a solvent, and reacting to obtain a gamma-ketosulfone compound with a structure shown in a formula III;
wherein R is 1 Selected from hydrogen, C1-C10 straight-chain alkyl, C1-C10 branched-chain alkyl, C3-C10 cyclic alkyl, substituted or unsubstituted C6-C20 aryl, and substituted or unsubstituted heterocyclic group containing nitrogen, oxygen and sulfur atoms; wherein, the substituent of the aryl or heterocyclic group is selected from C1-C10 straight-chain alkyl, C1-C10 branched-chain alkyl, C3-C10 cyclic alkyl, halogen, nitro or amino;
R 2 selected from C1-C10 straight-chain alkyl, C1-C10 branched-chain alkyl, C3-C10 cyclic alkyl, trifluoromethyl, substituted or unsubstituted C6-C20 aryl, and substituted or unsubstituted heterocyclic groups containing nitrogen, oxygen and sulfur atoms; wherein, the substituent of the aryl or heterocyclic group is selected from C1-C10 straight-chain alkyl, C1-C10 branched-chain alkyl, C3-C10 cyclic alkyl, halogen, nitro or amino;
R 4 selected from hydrogen, C1-C10 straight-chain alkyl, C1-C10 branched-chain alkyl, C3-C10 cyclic alkyl, substituted or unsubstituted C6-C20 aryl, trifluoromethyl, and substituted or unsubstituted heterocyclic group containing nitrogen, oxygen and sulfur atoms; wherein, the substituent of the aryl or heterocyclic group is selected from C1-C10 straight-chain alkyl, C1-C10 branched-chain alkyl, C3-C10 cyclic alkyl, halogen, nitro or amino.
In a certain aspect of the inventionIn some embodiments, R is 1 Selected from hydrogen, halogen substituted phenyl, methyl substituted phenyl, methoxy substituted phenyl, methylsulfonyl substituted phenyl, biphenyl, dimethylamino substituted phenyl, trifluoromethyl substituted phenyl, nitro substituted phenyl, anthracenyl, indolyl, benzyl or substituted quinolinyl.
In certain embodiments of the present invention, the R 1 One selected from the formulas R1-1 to R1-18;
in certain embodiments of the invention, the R is 2 Selected from phenyl, methyl-substituted phenyl, tert-butyl-substituted phenyl, methoxy-substituted phenyl, trifluoromethoxy-substituted phenyl, mesityl, halogen-substituted phenyl, trifluoromethyl-substituted phenyl, nitro-substituted phenyl, naphthyl, cyclopropylalkyl, chloroethyl or cycloalkyl containing a keto group.
In certain embodiments of the invention, the R is 2 One selected from the formulas R2-1 to R2-18;
in certain embodiments of the invention, the R is 4 Selected from hydrogen, methine or phenyl.
In certain embodiments of the invention, the gamma-ketosulfone compound having the structure shown in formula III is selected from one of formulas III-1 to III-37;
in certain embodiments of the present invention, the acid comprises at least one of acetic acid, formic acid, hydrochloric acid, nitric acid, benzoic acid, p-toluic acid, 4-acetylbenzoic acid, 4-fluorobenzoic acid, 4-chlorobenzoic acid, bromobenzoic acid, 4-nitrobenzoic acid, 2-naphthoic acid, and 2-nitrobenzoic acid.
In certain embodiments of the invention, the solvent comprises at least one of dimethyl sulfoxide, 1,4-dioxane, toluene, methanol, o-xylene, m-xylene, p-xylene, trifluorotoluene, and mesitylene.
In certain embodiments of the invention, the molar ratio of the acetylenic ketone compound having the structure of formula i to the compound having the structure of formula ii is 1:1 to 3; specifically, it may be 1: 1.1-2, more specifically 1:2 or 1:2.5.
in certain embodiments of the present invention, the molar ratio of the alkynone compound having the structure of formula i to the acid is 1:0.5 to 3; specifically, it may be 1: 1-2, more specifically 1:2 or 1:3.
in certain embodiments of the present invention, the acetylenic ketone compound having the structure of formula I and the solvent are used in a ratio of 0.02 to 0.07mol:1L; specifically, the content may be 0.067mol:1L of the compound.
In certain embodiments of the invention, the temperature of the reaction is 25 to 80 ℃, preferably 30 ℃; the reaction time is 24-48 h; specifically, the time period may be 48 hours. The reaction is carried out under an air atmosphere. The reaction is carried out with stirring.
In certain embodiments of the present invention, after the reacting, further comprising:
and filtering the product solution after the reaction, washing filter residues by using ethyl acetate, and performing reduced pressure concentration and column chromatographic separation on the obtained filtrate and washing liquid to obtain the gamma-ketosulfone compound with the structure shown in the formula III.
The filtration adopts a sand core funnel with silica gel.
The column chromatographic separation selects 200-300 mesh silica gel, the mobile phase selects petroleum ether and ethyl acetate, and the volume ratio is 3-5: 1; specifically, it may be 4:1.
the invention also provides another preparation method of the gamma-ketosulfone compound, which comprises the following steps:
mixing an ketene compound with a structure shown in a formula IV, a compound with a structure shown in a formula II, an acid and a solvent, and reacting to obtain a gamma-ketosulfone compound with a structure shown in a formula V;
wherein R is 1 Selected from hydrogen, C1-C10 straight-chain alkyl, C1-C10 branched-chain alkyl, C3-C10 cyclic alkyl, substituted or unsubstituted C6-C20 aryl, and substituted or unsubstituted heterocyclic group containing nitrogen, oxygen and sulfur atoms; wherein, the substituent of the aryl or heterocyclic group is selected from C1-C10 straight-chain alkyl, C1-C10 branched-chain alkyl, C3-C10 cyclic alkyl, halogen, nitro or amino;
R 2 selected from C1-C10 straight-chain alkyl, C1-C10 branched-chain alkyl, C3-C10 cyclic alkyl, trifluoromethyl, substituted or unsubstituted C6-C20 aryl, and substituted or unsubstituted heterocyclic groups containing nitrogen, oxygen and sulfur atoms; wherein, the substituent of the aryl or heterocyclic group is selected from C1-C10 straight-chain alkyl, C1-C10 branched-chain alkyl, C3-C10 cyclic alkyl, halogen, nitro or amino;
R 3 selected from hydrogen, C1-C10 straight-chain alkyl, C1-C10 branched-chain alkyl and C3-C10 cyclic alkyl;
R 4 selected from hydrogen, C1-C10 straight-chain alkyl, C1-C10 branched-chain alkyl, C3-C10 cyclic alkyl, substituted or unsubstituted C6-C20Aryl, trifluoromethyl, substituted or unsubstituted heterocyclic group containing nitrogen, oxygen, sulfur atoms; wherein, the substituent of the aryl or heterocyclic group is selected from C1-C10 straight-chain alkyl, C1-C10 branched-chain alkyl, C3-C10 cyclic alkyl, halogen, nitro or amino.
In certain embodiments of the present invention, the R 1 Selected from hydrogen, phenyl, methoxy substituted phenyl, biphenyl, halogen substituted phenyl, cyano substituted phenyl, nitro substituted phenyl or pentyl.
In certain embodiments of the present invention, the R 1 One selected from the group consisting of r1-1 to r 1-8;
in certain embodiments of the invention, the R is 2 Selected from phenyl or methyl substituted phenyl.
In certain embodiments of the invention, the R is 2 One selected from the group consisting of r2-1 to r 2-2;
in certain embodiments of the invention, the gamma-ketosulfone compound having the structure of formula V is selected from one of formulas V-1 to V-11;
in certain embodiments of the present invention, the acid comprises at least one of acetic acid, formic acid, hydrochloric acid, nitric acid, benzoic acid, p-toluic acid, 4-acetylbenzoic acid, 4-fluorobenzoic acid, 4-chlorobenzoic acid, bromobenzoic acid, 4-nitrobenzoic acid, 2-naphthoic acid, and 2-nitrobenzoic acid.
In certain embodiments of the invention, the solvent comprises at least one of dimethyl sulfoxide, 1,4-dioxane, toluene, methanol, o-xylene, m-xylene, p-xylene, trifluorotoluene, and mesitylene.
In certain embodiments of the present invention, the molar ratio of the ketene compound having the structure shown in formula iv to the compound having the structure shown in formula ii is 1:1 to 3; specifically, it may be 1: 1.1-2, more specifically 1:2 or 1:2.5.
in certain embodiments of the present invention, the molar ratio of the alkenone compound having the structure of formula iv to the acid is 1:0.5 to 3, specifically, 1: 1-2, more specifically 1:2 or 1:3.
in some embodiments of the present invention, the ketene compound having the structure shown in formula IV and the solvent are used in a ratio of 0.02 to 0.07mol:1L; specifically, the molar ratio may be 0.067mol:1L of the compound.
In certain embodiments of the invention, the temperature of the reaction is 25 to 80 ℃, preferably 30 ℃; the reaction time is 12 to 48 hours; specifically, the time can be 48h. The reaction is carried out under an air atmosphere.
In certain embodiments of the present invention, after the reacting, further comprising:
and filtering the product solution after the reaction, washing filter residues by using ethyl acetate, and performing reduced pressure concentration and column chromatographic separation on the obtained filtrate and washing liquid to obtain the gamma-ketosulfone compound with the structure shown in the formula III.
The filtration adopts a sand core funnel with silica gel.
The column chromatographic separation selects 200-300 mesh silica gel, the mobile phase selects petroleum ether and ethyl acetate, and the volume ratio is 3-5: 1; specifically, the ratio of 4:1.
the preparation method of the gamma-ketosulfone compound provided by the invention does not need to use a catalyst, an oxidant and peroxide.
The invention overcomes the defects that the existing synthesis method of the gamma-ketone sulfone compound has complex synthesis steps, can be completed by adopting a multi-step synthesis process, and needs to use a metal catalyst, a chemical equivalent oxidant or peroxide and the like; the atom economy is kept to the utmost extent; the compound has stable molecular structure and excellent chemical property, and the molecular cut block and the compound fragment contain rich contents of biological activity and pharmacological activity; the method has the characteristics of simple reaction system, mild reaction conditions, few steps, few reaction equipment, simple and convenient experimental operation, wide material sources, low price and easy obtainment, easy expansion of users and application, higher product utilization value, expected market commercialization prospect and the like.
The raw material sources adopted by the invention are not particularly limited, and the raw materials can be generally sold in the market; or prepared by the existing preparation method.
The invention overcomes the defects that the existing synthesis method of the gamma-ketosulfone compound has complex synthesis steps, can be completed by adopting a multi-step synthesis process, and also needs to use a metal catalyst, a chemical equivalent oxidant or peroxide and the like; the atom economy is kept to the utmost extent; the compound has stable molecular structure and excellent chemical property, and molecular blocks and compound fragments contain rich contents of biological activity and pharmacological activity; the method has the characteristics of simple reaction system, mild reaction conditions, few steps, few reaction equipment, simple and convenient experimental operation, wide material sources, low price, easy obtainment, easy expansion of users and application, higher product utilization value, expected market commercialization prospect and the like.
Drawings
FIG. 1 is a nuclear magnetic resonance hydrogen spectrum of a target product prepared in example 4 of the present invention;
FIG. 2 is a nuclear magnetic resonance carbon spectrum of a target product prepared in example 4 of the present invention;
FIG. 3 is a NMR spectrum of a target product prepared in example 40 of the present invention;
FIG. 4 is a NMR carbon spectrum of a target product prepared in example 40 of the present invention.
Detailed Description
The technical solutions of the present invention will be described clearly and completely with reference to the following embodiments of the present invention, and it should be understood that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be obtained by a person skilled in the art without making any creative effort based on the embodiments in the present invention, belong to the protection scope of the present invention.
The starting materials used in the following examples are all commercially available.
Example 1
The results of examining the influence of acid on the reaction yield in the reaction for synthesizing (E) - α, β -unsaturated γ -ketosulfone compound 3fa using E-1- (4-fluorophenyl) -2-propyn-1-one 1f (prepared in reference (org. Lett.2016,18,15,3554-3557) and sodium benzenesulfonate 2a as standard substrates are shown in table 1;
at 30 ℃ 1f was 0.2mmol,1f/2a molar ratio 1:2.5,3mL of toluene solvent for 48h,3 equivalents of material of acid (relative to 1f of material); wherein PCBA represents 4-chlorobenzoic acid, PNBA represents 4-nitrobenzoic acid; yield refers to the total separation yield of the compound containing (E) -alpha, beta-unsaturated gamma-ketone sulfone; E/Z refers to the trans-to cis-ratio of the olefin, as determined by reversed phase high performance liquid chromatography.
TABLE 1 Effect of acid on reaction yield
Example 2
The results of the study on the influence of the solvent on the reaction yield in the reaction for synthesizing the (E) -alpha, beta-unsaturated gamma-ketosulfone compound 3fa by using 1- (4-fluorophenyl) -2-propyn-1-one 1f and sodium benzene sulfinate 2a as standard substrates are shown in Table 2;
at 30 ℃ 1f was 0.2mmol,1f/2a molar ratio 1:2.5, reacting in the solvent shown in Table 2 for 48 hours, wherein the using amount of the solvent is 3 mL; wherein the acid in the reaction system is 4-chlorobenzoic acid (PCBA), 3 equivalents mass of acid (relative to mass of 1 f); yield refers to the total separation yield of the compound containing (E) -alpha, beta-unsaturated gamma-ketosulfone. E/Z refers to the trans-to cis-ratio of the olefin, as determined by reversed phase high performance liquid chromatography. Wherein o-Xylene means o-Xylene, p-Xylene means p-Xylene, m-Xylene means m-Xylene, DMF means N, N' -dimethylformamide, meOH means methanol, and Mesitylene means Mesitylene.
TABLE 2 influence of solvent on reaction yield
Example 3
The results of studying the influence of the molar ratio of acid to the raw material 1f, the molar ratio of 1f to 2a, and the temperature on the reaction yield in the reaction for synthesizing the (E) -alpha, beta-unsaturated gamma-ketosulfone compound 3fa by using E-1- (4-fluorophenyl) -2-propyn-1-one 1f and sodium benzenesulfonate 2a as standard substrates are shown in Table 3;
reacting at 30 ℃ in a mesitylene solvent with 1f of 0.2mmol and 3mL for 48h, wherein the acid in the reaction system is 4-chlorobenzoic acid (PCBA); equiv represents equivalent; yield refers to the total separation yield of the compound containing (E) -alpha, beta-unsaturated gamma-ketosulfone. E/Z refers to the trans-to cis-ratio of the olefin, as determined by reversed phase high performance liquid chromatography.
TABLE 3 influence of the molar ratio of acid to starting material 1f, the molar ratio of 1f to 2a and the temperature on the reaction yield
| entry | Acid(Xeq.) | 2a/1f | temp.(℃) | yield(％) | E/Z |
| 1 | 2.0 | 2.5 | 30 | 85 | 95:05 |
| 2 | 1.2 | 2.5 | 30 | 76 | 91:09 |
| 3 | 0.5 | 2.5 | 30 | 44 | 73:27 |
| 4 | 2.0 | 2.0 | 30 | 79 | 90:10 |
| 5 | 2.0 | 2.5 | 80 | 53 | 97:03 |
Example 4
Preparation of (E) -3- (phenylsulfonyl) -1-phenyl-2-propen-1-one ((E) -1-phenyl-3- (phenylsulfonyl) prop-2-en-1-one) having the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6mg, 0.4 mmol), 1-phenyl-2-propyn-1-one (26.0mg, 0.2mmol) and sodium benzenesulfinate (82.1mg, 0.5 mmol) were weighed in a 10mLSchlen tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then, the mixture was sealed and reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system by a sand core funnel with silica gel, washing filter residues by 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating by column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the obtained target product is a yellow solid; a yield of 97%; rf =0.5 (PE: EA = 4:1).
The structural characterization data is as follows:
1 H NMR(500MHz,CDCl3)δ8.04(d,J＝8.5Hz,1H),8.00-7.92(m,4H),7.70-7.59(m,3H),7.54(t,J＝7.8Hz,2H),7.46(d,J＝8.5Hz,1H),7.36(d,J＝14.9Hz,1H)； 13 C NMR(126MHz,CDCl 3 )δ187.63,141.97,138.56,135.95,134.51,134.38,133.03,129.66,129.09,128.98,128.29。
the target product was subjected to nmr hydrogen spectroscopy, and the results are shown in fig. 1. FIG. 1 is a NMR chart of a target product prepared in example 4 of the present invention.
The target product was subjected to nmr carbon spectroscopy, and the results are shown in fig. 2. FIG. 2 is the NMR spectrum of the target product prepared in example 4 of the present invention.
Example 5
Preparation of (E) -3- (phenylsulfonyl) -1- (p-tolyl) -2-propen-1-one ((E) -3- (phenylsulfonyl) -1- (p-tolyl) prop-2-en-1-one) having the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6 mg,0.4 mmol), 1- (4-methyl) phenyl-2-propyn-1-one (28.4 mg, 0.2mmol) and sodium benzenesulfinate (82.1mg, 0.5 mmol) were weighed into a 10mLSchlen tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then sealed and reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system through a sand core funnel with silica gel, washing filter residues with 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating the residues through column chromatography to obtain a pyridine product; the column chromatography separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the obtained target product is a white solid; a yield of 98%; rf =0.4 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl3)δ7.97-7.88(m,5H),7.68(t,J＝7.4Hz,1H),7.59(t,J＝7.7Hz,2H),7.34(dd,J＝18.4,11.4Hz,3H),2.44(s,3H)； 13 C NMR(126MHz,CDCl3)δ187.09,145.81,141.63,138.72,134.35,133.57,133.32,129.82,129.67,129.16,128.28,21.89。
Example 6
Preparation of (E) -3- (benzenesulfonyl) -1- (p-methoxyphenyl) -2-propen-1-one ((E) -1- (4-methoxyphenyl) -3- (phenylsulfonyl) prop-2-en-1-one) having the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6 mg,0.4 mmol), 1- (4-methoxy) phenyl-2-propyn-1-one (32.0mg, 0.2mmol) and sodium benzenesulfinate (82.1mg, 0.5 mmol) were weighed in a 10mL Schlenk tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then, the mixture was sealed and reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system by a sand core funnel with silica gel, washing filter residues by 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating by column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the obtained target product is a white solid; 71% yield; rf =0.5 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl 3 )δ7.93-7.85(m,5H),7.61(t,J＝7.4Hz,1H),7.52(t,J＝7.7Hz,2H),7.28-7.19(m,1H),6.92(d,J＝8.9Hz,2H),3.83(s,3H)； 13 C NMR(126MHz,CDCl 3 )δ184.70,163.71,140.25,137.83,133.23,132.37,130.51,128.60,128.13,127.22,113.34,54.65。
Example 7
In this example, (E) -3- (benzenesulfonyl) -1- (p-methylthiophenyl) -2-propen-1-one ((E) -1- (4- (methylthiohio) phenyl) -3- (phenylsulfonyl) prop-2-en-1-one) was prepared, having the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6 mg,0.4 mmol), 1- (4-thiomethyl) phenyl-2-propyn-1-one (35.3 mg, 0.2mmol) and sodium benzenesulfinate (82.1mg, 0.5 mmol) were weighed into a 10mL Schlenk tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then, the mixture was sealed and reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system by a sand core funnel with silica gel, washing filter residues by 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating by column chromatography to obtain a pyridine product; the column chromatography separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the obtained target product is a yellow solid with 82% yield; rf =0.3 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl 3 )δ7.84(dd,J＝28.5,8.2Hz,5H),7.60(t,J＝7.1Hz,1H),7.51(t,J＝7.3Hz,2H),7.28(d,J＝14.8Hz,1H),7.21(d,J＝8.1Hz,2H),2.45(s,3H)； 13 C NMR(126MHz,CDCl 3 )δ186.22,148.51,141.64,138.65,134.39,133.04,132.14,129.69,129.36,128.29,125.06,14.62。
Example 8
In this example, (E) -3- (benzenesulfonyl) -1-biphenyl-2-propen-1-one ((E) -1- ([ 1,1' -biphenyl ] -4-yl) -3- (phenylsulfonyl) prop-2-en-1-one) was prepared, having the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6 mg,0.4 mmol), 1- (4-phenyl) phenyl-2-propyn-1-one (41.25mg, 0.2mmol) and sodium benzenesulfinate (82.1mg, 0.5 mmol) were weighed into a 10mL Schlenk tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then, after sealing, reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system through a sand core funnel with silica gel, washing filter residues with 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating the residues through column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the target product was obtained as a yellow solid in 94% yield; rf =0.5 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl 3 )δ8.08-7.96(m,5H),7.75(d,J＝8.3Hz,2H),7.70(t,J＝7.5Hz,1H),7.65(d,J＝7.2Hz,2H),7.60(dd,J＝15.8,8.1Hz,2H),7.50(t,J＝7.4Hz,2H),7.46-7.38(m,2H)； 13 C NMR(126MHz,CDCl 3 )δ187.10,147.24,141.92,139.37,138.63,134.69,134.43,133.09,129.72,129.68,129.12,128.72,128.34,127.71,127.38。
Example 9
In this example, the preparation of (E) -3- (benzenesulfonyl) -1- (p-fluorophenyl) -2-propen-1-one ((E) -1- ([ 1,1' -biphenyl ] -4-yl) -3- (phenylsulfonyl) prop-2-en-1-one) has the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6 mg,0.4 mmol), 1- (4-fluoro) phenyl-2-propyn-1-one (29.6 mg, 0.2mmol) and sodium benzenesulfinate (82.1mg, 0.5 mmol) were weighed into a 10mLSchlenk tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then, after sealing, reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system through a sand core funnel with silica gel, washing filter residues with 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating the residues through column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the obtained target product is a yellow solid with 85% yield; rf =0.4 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl 3 )δ8.05-8.03(m,2H),7.96(d,J＝7.8Hz,2H),7.91(d,J＝14.9Hz,1H),7.70(t,J＝7.4Hz,1H),7.61(t,J＝7.7Hz,2H),7.37(d,J＝14.9Hz,1H),7.21(t,J＝8.4Hz,2H)； 13 C NMR(126MHz,CDCl 3 )δ186.02,166.54(d,J＝257.8Hz),142.25,138.58,134.43,132.68,132.49(d,J＝2.8Hz),131.81(d,J＝9.8Hz),129.70,128.32,116.42(d,J＝22.1Hz)； 19 F NMR(471MHz,CDCl 3 )δ-101.93。
Example 10
In this example, (E) -3- (benzenesulfonyl) -1- (p-chlorophenyl) -2-propen-1-one ((E) -1- (4-chlorophenyl) -3- (phenylsulfonyl) prop-2-en-1-one) was prepared, having the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6 mg,0.4 mmol), 1- (4-chloro) phenyl-2-propyn-1-one (32.9 mg,0.2 mmol) and sodium benzenesulfinate (82.1mg, 0.5 mmol) were weighed into a 10mL Schlenk tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then sealed and reacted at 30 ℃ for 48h. Filtering the reacted mixed system by a sand core funnel with silica gel, washing filter residues by 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating by column chromatography to obtain a pyridine product; the column chromatography separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the obtained target product was a white solid with a yield of 93%; rf =0.6 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl 3 )δ7.97-7.89(m,5H),7.70(t,J＝7.3Hz,1H),7.61(t,J＝7.6Hz,2H),7.51(d,J＝8.4Hz,2H),7.38(d,J＝14.9Hz,1H)； 13 CNMR(126MHz,CDCl 3 )δ186.44,142.44,141.20,138.47,134.50,134.31,132.45,130.37,129.74,129.50,128.34。
Example 11
In this example, (E) -3- (phenylsulfonyl) -1- (p-bromophenyl) -2-propen-1-one ((E) -1- (4-bromophenyl) -3- (phenylsulfonyl) prop-2-en-1-one) was prepared, having the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6 mg,0.4 mmol), 1- (4-bromo) phenyl-2-propyn-1-one (28.4 mg, 0.2mmol) and sodium benzenesulfinate (82.1mg, 0.5 mmol) were weighed into a 10mLSchlen tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then sealed and reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system through a sand core funnel with silica gel, washing filter residues with 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating the residues through column chromatography to obtain a pyridine product; the column chromatography separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the obtained target product is a white solid with a yield of 97%; rf =0.4 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl 3 )δ7.88(d,J＝7.7Hz,2H),7.79(dd,J＝13.9,11.9Hz,3H),7.61(dd,J＝16.1,7.9Hz,3H),7.53(t,J＝7.7Hz,2H),7.31-7.19(m,1H)； 13 C NMR(126MHz,CDCl 3 )δ185.63,141.47,137.50,133.70,133.42,131.45,131.38,129.33,128.99,128.67,127.29。
Example 12
In this example, (E) -3- (phenylsulfonyl) -1- (p-iodophenyl) -2-propen-1-one ((E) -1- (4-iodophenyl) -3- (phenylsulfonyl) prop-2-en-1-one) was prepared, having the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6 mg,0.4 mmol), 1- (4-iodo) phenyl-2-propyn-1-one (51.2 mg,0.2 mmol) and sodium benzenesulfinate (82.1mg, 0.5 mmol) were weighed into a 10mL Schlenk tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then sealed and reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system by a sand core funnel with silica gel, washing filter residues by 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating by column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the target product was obtained as a white solid in 86% yield; rf =0.6 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl 3 )δ7.88(d,J＝6.4Hz,2H),7.81(t,J＝10.8Hz,3H),7.62(d,J＝6.6Hz,3H),7.53(s,2H),7.32-7.19(m,1H)； 13 C NMR(126MHz,CDCl 3 )δ187.01,142.48,138.48,138.24,135.23,134.51,132.34,130.16,129.74,128.35,103.15。
Example 13
In this example, (E) -3- (benzenesulfonyl) -1- (4- (N, N-dimethyl) phenyl) -2-propen-1-one ((E) -1- (4- (dimethyllamino) phenyl) -3- (phenylsulfonyl) prop-2-en-1-one) was prepared, having the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6 mg,0.4 mmol), 1- (4- (N, N-dimethyl)) phenyl-2-propyn-1-one (34.7 mg, 0.2mmol) and sodium benzenesulfinate (82.1mg, 0.5 mmol) were weighed into a 10mLSchlen tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then, after sealing, reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system by a sand core funnel with silica gel, washing filter residues by 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating by column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the target product was obtained as a red solid in 73% yield; rf =0.2 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl 3 )δ7.99-7.91(m,5H),7.67(t,J＝7.2Hz,1H),7.58(t,J＝7.5Hz,2H),7.34-7.27(m,1H),6.67(d,J＝8.7Hz,2H),3.10(s,6H)； 13 C NMR(126MHz,CDCl 3 )δ184.09,154.26,139.87,139.10,134.14,134.12,131.61,129.57,128.80,128.18,124.01,111.00,40.11。
Example 14
In this example, (E) -3- (benzenesulfonyl) -1- (4-trifluoromethylphenyl) -2-propen-1-one ((E) -3- (phenylsulfonyl) -1- (4- (trifluoromethyl) phenyl) prop-2-en-1-one) was prepared, having the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6 mg,0.4 mmol), 1- (4-trifluoromethyl) phenyl-2-propyn-1-one (39.6 mg, 0.2mmol) and sodium benzenesulfinate (82.1mg, 0.5 mmol) were weighed into a 10mL Schlenk tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then sealed and reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system by a sand core funnel with silica gel, washing filter residues by 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating by column chromatography to obtain a pyridine product; the column chromatography separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the obtained target product is a yellow solid with a yield of 95%; rf =0.4 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl 3 )δ8.10(d,J＝7.8Hz,2H),7.95(dd,J＝21.2,11.5Hz,4H),7.79(d,J＝7.9Hz,2H),7.61(t,J＝7.4Hz,2H),7.42(d,J＝14.9Hz,1H)； 13 C NMR(126MHz,CDCl 3 )δ186.95,143.05,138.60,138.36,135.46(d,J＝32.9Hz),134.57,132.21,129.76,129.30,128.36,126.14(q,J＝3.8Hz),123.35(q,J＝273.0Hz)； 19 F NMR(471MHz,CDCl 3 )δ-63.22。
Example 15
In this example, (E) -3- (benzenesulfonyl) -1- (2-nitrophenyl) -2-propen-1-one ((E) -1- (2-nitrophenyl) -3- (phenylsulfonyl) prop-2-en-1-one) was prepared and has the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6 mg,0.4 mmol), 1- (2-nitro) phenyl-2-propyn-1-one (35.0 mg, 0.2mmol) and sodium benzenesulfinate (82.1mg, 0.5 mmol) were weighed into a 10mL Schlenk tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then, the tube was sealed and reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system through a sand core funnel with silica gel, washing filter residues with 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating the residues through column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the target product was obtained as a white solid in 71% yield; rf =0.4 (PE: EA = 2:1).
1 H NMR(500MHz,CDCl 3 )δ8.18(d,J＝8.2Hz,1H),7.90(d,J＝7.7Hz,2H),7.80(t,J＝7.5Hz,1H),7.71(dd,J＝11.9,7.5Hz,2H),7.60(t,J＝7.8Hz,2H),7.48(d,J＝7.5Hz,1H),7.29-7.26(m,1H),7.04(d,J＝15.3Hz,1H)； 13 C NMR(126MHz,CDCl 3 )δ189.52,146.20,141.24,138.18,135.71,134.90,134.81,134.59,132.00,129.76,128.82,128.34,124.76。
Example 16
In this example, (E) -3- (benzenesulfonyl) -1- (5-anthracenyl) -2-propen-1-one ((E) -1- (anthracenyl-9-yl) -3- (phenylsulfonyl) prop-2-en-1-one) was prepared, having the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6 mg,0.4 mmol), 1-anthryl-2-propyn-1-one (46.1mg, 0.2mmol) and sodium benzenesulfinate (82.1mg, 0.5 mmol) were weighed into a 10mLSchlen tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then sealed and reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system by a sand core funnel with silica gel, washing filter residues by 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating by column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the target product was obtained as a red solid with a yield of 94%; rf =0.4 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl 3 )δ8.56(s,1H),8.05-8.03(m,2H),7.86(d,J＝7.6Hz,2H),7.76-7.74(m,2H),7.66(t,J＝7.3Hz,1H),7.56-7.48(m,7H),7.07(d,J＝15.3Hz,1H)； 13 C NMR(126MHz,CDCl 3 )δ196.41,142.94,138.38,137.90,134.48,131.95,130.94,130.59,129.68,129.07,128.40,128.31,127.69,125.81,124.28。
Example 17
In this example, (E) -3- (benzenesulfonyl) -1- (2-methylphenyl) -2-propen-1-one ((E) -3- (phenylsulfonyl) -1- (o-tolyl) prop-2-en-1-one) was prepared, having the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6mg, 0.4 mmol), 1- (2-methyl) phenyl-2-propyn-1-one (28.8mg, 0.2mmol) and sodium benzenesulfinate (82.1mg, 0.5 mmol) were weighed into a 10mLSchlen tube with magnetons, 3.0mL of mesitylene was added thereto using a pipette, and then, the mixture was sealed and reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system through a sand core funnel with silica gel, washing filter residues with 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating the residues through column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the target product was obtained as a white solid in 71% yield; rf =0.4 (PE: EA = 2:1). The target product was obtained as a white solid in 82% yield; rf =0.6 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl 3 )δ7.95(d,J＝7.8Hz,2H),7.71-7.58(m,5H),7.46(t,J＝7.4Hz,1H),7.33-7.27(m,2H),7.22(d,J＝15.0Hz,1H),2.48(s,3H)； 13 C NMR(126MHz,CDCl 3 )δ191.07,141.73,139.41,138.61,136.14,135.88,134.42,132.80,132.27,129.78,129.70,128.31,126.02,21.19。
Example 18
In this example, (E) -3- (phenylsulfonyl) -1- (3-methylphenyl) -2-propen-1-one ((E) -3- (phenylsulfonyl) -1- (m-tolyl) prop-2-en-1-one) was prepared, having the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6mg, 0.4 mmol), 1- (3-methyl) phenyl-2-propyn-1-one (28.8mg, 0.2mmol) and sodium benzenesulfinate (82.1mg, 0.5 mmol) were weighed into a 10mLSchlen tube with magnetons, 3.0mL of mesitylene was added thereto using a pipette, and then, the mixture was sealed and reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system by a sand core funnel with silica gel, washing filter residues by 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating by column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the target product was obtained as a white solid in 71% yield; rf =0.4 (PE: EA = 2:1). The target product was obtained as a yellow solid in 94% yield; rf =0.4 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl 3 )δ7.96(dd,J＝10.7,5.9Hz,3H),7.79(d,J＝8.4Hz,2H),7.69(t,J＝7.1Hz,1H),7.60(t,J＝7.5Hz,2H),7.46(d,J＝7.2Hz,1H),7.43-7.35(m,2H),2.43(s,3H)； 13 C NMR(126MHz,CDCl 3 )δ187.74,141.79,139.10,138.63,136.01,135.38,134.41,133.27,129.70,129.46,128.99,128.31,126.28,21.39。
Example 19
In this example, (E) -3- (benzenesulfonyl) -1- (2-indolyl) -2-propen-1-one ((E) -1- (1H-indol-3-yl) -3- (phenylsulfonyl) prop-2-en-1-one) was prepared, which has the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6mg, 0.4 mmol), 2-indolyl-2-propyn-1-one (33.8mg, 0.2mmol) and sodium benzenesulfinate (82.1mg, 0.5 mmol) were weighed into a 10mLSchlen tube with magnetons, 3.0mL of mesitylene was added thereto using a pipette, and then the mixture was sealed and reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system by a sand core funnel with silica gel, washing filter residues by 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating by column chromatography to obtain a pyridine product; the column chromatography separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the target product was obtained as a white solid in 71% yield; rf =0.4 (PE: EA = 2:1). The target product was obtained as a yellow solid in 76% yield; rf =0.4 (PE: EA = 3:1).
1 H NMR(500MHz,CDCl 3 )δ8.69(s,6H),8.20(d,J＝3.5Hz,11H),7.90(s,12H),7.71(s,3H),7.61(s,11H),7.48(d,J＝5.0Hz,8H),7.19(s,10H),6.98(s,3H)； 13 C NMR(126MHz,CDCl 3 )δ179.98,146.82,140.81,135.01,132.62,132.35,129.00,128.62,125.23,122.93,122.34,120.59,119.85,119.44,112.34。
Example 20
In this example, (E) -1-phenyl-4- (phenylsulfonyl) -3-propen-3-one ((E) -1-phenyl-4- (phenylsulfonyl) but-3-en-2-one) was prepared, having the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6 mg,0.4 mmol), 1-benzyl-2-propyn-1-one (28.8 mg,0.2 mmol) and sodium benzenesulfinate (82.1mg, 0.5 mmol) were weighed into a 10mL Schlenk tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then, after sealing, reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system by a sand core funnel with silica gel, washing filter residues by 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating by column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the target product was obtained as a white solid in 71% yield; rf =0.4 (PE: EA = 2:1). The target product was obtained as a white solid in 80% yield; rf =0.4 (PE: EA = 5:1).
1 H NMR(500MHz,CDCl 3 )δ7.84(s,4H),7.65(s,1H),7.55(s,3H),7.22-7.13(m,9H),6.93(s,1H),4.34(s,4H)； 13 C NMR(126MHz,CDCl 3 )δ197.06,144.54,140.81,134.55,132.62,130.75,130.45,129.00,128.67,128.62,126.65,44.91。
Example 21
In this example, (E) -1- (2-cycloprophyl-4- (4-fluorophenyl) quinolin-3-yl) -3- (phenylsulfonyl) prop-2-en-1-one was prepared, having the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6 mg,0.4 mmol), 1- (2-cyclopropyl-4- (4-fluorophenyl) quinolin-3-yl) -2-propyn-1-one (63.1mg, 0.2mmol) and sodium benzenesulfinate (82.1mg, 0.5 mmol) were weighed into a 10mLSchlenk tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then, after sealing, reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system by a sand core funnel with silica gel, washing filter residues by 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating by column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the target product was obtained as a white solid in 71% yield; rf =0.4 (PE: EA = 2:1). The target product was obtained as a white solid in 79% yield; rf =0.4 (PE: EA = 5:1).
1 H NMR(500MHz,CDCl 3 )δ8.12(s,10H),7.90(s,22H),7.76(s,10H),7.71(s,6H),7.61(s,21H),7.54-7.47(m,24H),7.39(s,27H),7.15(s,21H),6.98(s,5H),2.22(s,4H),1.24(s,9H),0.99(s,9H)； 13 C NMR(126MHz,CDCl 3 )δ181.84,163.68,158.79,158.62,146.43,144.80,140.81,132.62,131.54,130.74,129.00,128.98,128.73,128.62,128.57,127.71,125.70,125.67,125.03,114.63,103.79,15.41,10.82。
Example 22
In this example, 3- (phenylsulfonyl) -1,3-diphenyl) -2-propen-1-one (1,3-diphenyl-3- (phenylsulfonyl) prop-2-en-1-one) was prepared, having the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6 mg,0.4 mmol), 1,3-diphenylpropyl-2-propyn-1-one (41.24mg, 0.2mmol) and sodium benzenesulfinate (82.1mg, 0.5 mmol) were weighed into a 10mLSchlen tube with magnetons, 3.0mL mesitylene was added with a pipette, and then reacted at 30 ℃ for 48 hours after sealing. Filtering the reacted mixed system through a sand core funnel with silica gel, washing filter residues with 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating the residues through column chromatography to obtain a pyridine product; the column chromatography separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the target product was obtained as a white solid in 71% yield; rf =0.4 (PE: EA = 2:1). The obtained target product is a green solid with 86% yield; rf =0.4 (PE: EA = 4:1).
1 H NMR(600MHz,CDCl3)δ7.98(s,1H),7.83(d,J＝7.5Hz,2H),7.65(d,J＝7.6Hz,2H),7.57-7.51(m,2H),7.45-7.36(m,4H),7.21(t,J＝7.3Hz,1H),7.13(t,J＝7.6Hz,2H),7.08(d,J＝7.5Hz,2H). 13 C NMR(125MHz,CDCl3)δ191.2,150.7,137.7,135.9,134.1,133.8,133.5,130.2,129.5,129.4,129.00,128.96,128.9,128.7,128.0。
Example 23
In this example, (E) -3- (4-tosyl) -1-phenyl-2-propen-1-one ((E) -1-phenyl-3-tosylprop-2-en-1-one) was prepared, which has the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6mg, 0.4 mmol), 1-phenyl-2-propyn-1-one (26.0 mg, 0.2mmol) and sodium 4-methylbenzenesulfinate (89mg, 0.5 mmol) were weighed into a 10mL Schlenk tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then sealed and reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system by a sand core funnel with silica gel, washing filter residues by 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating by column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the obtained target product is a yellow solid with a yield of 70%; rf =0.4 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl 3 )δ7.98(d,J＝7.8Hz,2H),7.90(d,J＝14.9Hz,1H),7.83(d,J＝8.1Hz,2H),7.64(t,J＝7.4Hz,1H),7.52(t,J＝7.7Hz,2H),7.36(dd,J＝15.4,11.6Hz,3H),2.45(s,3H)； 13 C NMR(126MHz,CDCl 3 )δ187.77,145.61,142.33,136.08,135.70,134.41,132.66,130.31,129.07,128.96,128.34,21.73。
Example 24
In this example, (E) -3- (4-tert-butylbenzenesulfonyl) -1-phenyl-2-propen-1-one ((E) -3- ((4- (tert-butyl) phenyl) sulfonyl) -1-phenylprop-2-en-1-one) was prepared, having the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6mg, 0.4 mmol), 1-phenyl-2-propyn-1-one (26.0mg, 0.2mmol) and sodium 4-tert-butylsulfinate (55.1mg, 0.5 mmol) were weighed into a 10mL Schlenk tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then, the mixture was sealed and reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system by a sand core funnel with silica gel, washing filter residues by 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating by column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the obtained target product is a white solid with a yield of 60%; rf =0.6 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl 3 )δ7.92-7.75(m,5H),7.58(t,J＝7.4Hz,1H),7.53-7.44(m,4H),7.3007.18(m,1H),1.28(s,9H)； 13 C NMR(126MHz,CDCl 3 )δ157.49,141.28,135.03,134.46,133.40,131.59,128.35,128.04,127.94,127.79,127.17,125.69,125.18,34.35,29.99。
Example 25
In this example, (E) -3- (4-methoxybenzenesulfonyl) -1-phenyl-2-propen-1-one ((E) -3- ((4-methoxyphenyl) sulfonyl) -1-phenylprop-2-en-1-one) was prepared, which has the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6mg, 0.4 mmol), 1-phenyl-2-propyn-1-one (26.0mg, 0.2mmol) and sodium 4-methoxybenzenesulfinate (48.5mg, 0.5mmol) were weighed into a 10mL Schlenk tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then, the tube was sealed and reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system by a sand core funnel with silica gel, washing filter residues by 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating by column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the target product was obtained as a yellow solid in 61% yield; rf =0.5 (PE: EA = 3:1).
1 H NMR(500MHz,CDCl 3 )δ7.99(d,J＝7.7Hz,1H),7.89-7.86(m,2H),7.65(t,J＝7.4Hz,1H),7.53(t,J＝7.7Hz,1H),7.36-7.26(m,1H),7.04(d,J＝8.8Hz,1H),3.90(s,2H)； 13 C NMR(126MHz,CDCl 3 )δ187.89,164.38,142.59,136.13,134.39,132.09,130.64,129.96,129.07,128.97,114.94,55.82。
Example 26
In this example, (E) -3- (4-trifluoromethoxybenzenesulfonyl) -1-phenyl-2-propen-1-one ((E) -1-phenyl-3- ((4- (trifluoromethyl) phenyl) sulfonyl) prop-2-en-1-one) was prepared, which has the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6mg, 0.4 mmol), 1-phenyl-2-propyn-1-one (26.0mg, 0.2mmol) and sodium 4-trifluoromethoxybenzenesulfinate (124.0mg, 0.5 mmol) were weighed in a 10mL Schlenk tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then, the tube was sealed and reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system by a sand core funnel with silica gel, washing filter residues by 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating by column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the target product was obtained as a white solid in 70% yield; rf =0.5 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl 3 )δ8.03-7.95(m,5H),7.68-7.65(m,1H),7.54(t,J＝7.8Hz,2H),7.41(d,J＝8.2Hz,2H),7.36(d,J＝14.9Hz,1H)； 13 C NMR(126MHz,CDCl 3 )δ187.44,153.48,153.47,141.49,136.94,135.91,134.61,133.78,130.68,129.15,129.02,121.36； 19 F NMR(471MHz,CDCl 3 )δ-57.64。
Example 27
In this example, (E) -3- (mesitylenesulfonyl) -1-phenyl-2-propen-1-one ((E) -3- (mesitylsultylfonyl) -1-phenylprop-2-en-1-one) was prepared, having the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6mg, 0.4 mmol), 1-phenyl-2-propyn-1-one (26.0mg, 0.2mmol) and 2,4,6-trimethylbenzenesulfinic acid sodium (103.3mg, 0.5 mmol) were weighed into a 10mL Schlenk tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then, after sealing, reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system by a sand core funnel with silica gel, washing filter residues by 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating by column chromatography to obtain a pyridine product; the column chromatography separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the target product was obtained as a white solid in 73% yield; rf =0.4 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl 3 )δ7.99-7.98(m,2H),7.88(d,J＝14.9Hz,1H),7.65(t,J＝7.4Hz,1H),7.53(t,J＝7.8Hz,2H),7.41(d,J＝14.9Hz,1H),6.99(s,2H),2.65(s,6H),2.32(s,3H)； 13 C NMR(126MHz,CDCl 3 )δ187.96,144.42,142.53,140.55,136.18,134.40,132.53,131.86,131.56,129.09,128.94,22.97,21.13。
Example 28
In this example, (E) -3- (4-fluorophenylsulfonyl) -1-phenyl-2-propen-1-one ((E) -3- ((4-fluorophenylyl) sulfonyl) -1-phenylprop-2-en-1-one) was prepared, which has the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6mg, 0.4 mmol), 1-phenyl-2-propyn-1-one (26.0mg, 0.2mmol) and sodium 4-fluorobenzenesulfonate (45.5mg, 0.5mmol) were weighed into a 10mLSchlen tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then, the mixture was sealed and reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system through a sand core funnel with silica gel, washing filter residues with 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating the residues through column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the obtained target product is a yellow solid, and the yield is 67%; rf =0.5 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl3)δ8.00-7.92(m,5H),7.67(t,J＝7.2Hz,1H),7.54(t,J＝7.7Hz,2H),7.34(d,J＝14.9Hz,1H),7.j27(dd,J＝11.3,5.2Hz,2H)； 13 C NMR(126MHz,CDCl 3 )δ187.55,166.25(d,J＝258.1Hz),141.81,135.96,134.56,133.28,131.32,131.24,129.13,129.00,117.09(d,J＝22.8Hz)； 19 F NMR(471MHz,CDCl 3 )δ-101.93.kk。
Example 29
In this example, (E) -3- (4-chlorobenzenesulfonyl) -1-phenyl-2-propen-1-one ((4-chlorophenylyl) sulfonyl) -1-phenylprop-2-en-1-one) was prepared, which has the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6mg, 0.4 mmol), 1-phenyl-2-propyn-1-one (26.0mg, 0.2mmol) and sodium 4-chlorophenylene sulfonate (49.7mg, 0.5 mmol) were weighed in a 10mLSchlenk tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then, the mixture was sealed and reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system by a sand core funnel with silica gel, washing filter residues by 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating by column chromatography to obtain a pyridine product; the column chromatography separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the obtained target product is a yellow solid with a yield of 72%; rf =0.6 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl 3 )δ8.00-7.98(m,1H),7.96-7.89(m,3H),7.67(dd,J＝10.6,4.2Hz,1H),7.58-7.52(m,4H),7.35(d,J＝14.9Hz,1H)； 13 C NMR(126MHz,CDCl 3 )δ187.47,141.59,141.31,137.19,135.93,134.58,133.58,130.05,129.77,129.14,129.00。
Example 30
In this example, (E) -3- (4-bromophenylsulfonyl) -1-phenyl-2-propen-1-one ((4-bromophenyl) sulfonyl) -1-phenylprop-2-en-1-one) was prepared, which has the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6mg, 0.4 mmol), 1-phenyl-2-propyn-1-one (26.0mg, 0.2mmol) and 4-bromobenzenesulfonic acid sodium salt (121.5mg, 0.5mmol) were weighed into a 10mLSchlenk tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then, the mixture was sealed and reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system through a sand core funnel with silica gel, washing filter residues with 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating the residues through column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the target product was obtained as a yellow solid in 73% yield; rf =0.6 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl 3 )δ7.92(s,2H),7.89-7.77(m,4H),7.69(s,2H),7.57(s,1H),7.49(s,2H)； 13 C NMR(125MHz,CDCl 3 )δ186.56,147.20,139.55,137.81,133.34,131.99,130.24,128.96,128.80,128.76,127.23。
Example 31
In this example, (E) -3- (4-iodobenzenesulfonyl) -1-phenyl-2-propen-1-one ((E) -3- ((4-iodophenyl) sulfonyl) -1-phenylprop-2-en-1-one) was prepared, having the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6mg, 0.4 mmol), 1-phenyl-2-propyn-1-one (26.0 mg, 0.2mmol) and sodium 4-iodobenzene sulfinate (145.1mg, 0.5 mmol) were weighed into a 10mL Schlenk tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then, after sealing, reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system by a sand core funnel with silica gel, washing filter residues by 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating by column chromatography to obtain a pyridine product; the column chromatography separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the target product was obtained as a yellow solid in 78% yield; rf =0.6 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl 3 )δ8.31(s,3H),7.98-7.71(m,3H),7.57(s,3H),7.49(s,2H)； 13 C NMR(125MHz,CDCl 3 )δ186.56,147.20,137.81,135.77,135.67,133.34,130.95,128.80,128.76,127.23,98.23。
Example 32
In this example, (E) -3- (4-trifluoromethylbenzenesulfonyl) -1-phenyl-2-propen-1-one ((E) -1-phenyl-3- ((4- (trifluoromethyl) phenyl) sulfonyl) prop-2-en-1-one) was prepared, having the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6 mg,0.4 mmol), 1-phenyl-2-propyn-1-one (26.0 mg,0.2 mmol) and sodium 4-trifluoromethylbenzenesulfinate (116.1mg, 0.5 mmol) were weighed into a 10mL Schlenk tube with magnetons, 3.0mL mesitylene was added with a pipette, and then, after sealing, reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system by a sand core funnel with silica gel, washing filter residues by 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating by column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the target product was obtained as a yellow solid in 83% yield; rf =0.6 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl 3 )δ8.10(d,J＝8.2Hz,2H),8.01-7.99(m,3H),7.87(d,J＝8.2Hz,2H),7.67(t,J＝7.4Hz,1H),7.55(t,J＝7.7Hz,2H),7.35(d,J＝14.9Hz,1H)； 13 C NMR(126MHz,CDCl 3 )δ187.26,142.35,141.05,135.98(q,J＝34.2Hz),135.84,134.67,134.49,129.18,129.02,128.92,126.82(q,J＝3.6Hz),123.00(q,J＝273.1Hz)； 19 F NMR(471MHz,CDCl 3 )δ-63.28。
Example 33
In this example, (E) -3- (4-nitrobenzenesulfonyl) -1-phenyl-2-propen-1-one ((E) -3- ((4-nitrophenyl) sulfonyl) -1-phenylproprop-2-en-1-one) was prepared, which has the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6mg, 0.4 mmol), 1-phenyl-2-propyn-1-one (26.0mg, 0.2mmol) and sodium 4-nitrobenzenesulfinate (104.6mg, 0.5 mmol) were weighed into a 10mLSchlenk tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then, the mixture was sealed and reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system through a sand core funnel with silica gel, washing filter residues with 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating the residues through column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the target product was obtained as a white solid in 85% yield; rf =0.3 (PE: EA = 3:1).
1 H NMR(500MHz,CDCl 3 )δ8.36(d,J＝8.7Hz,2H),8.10(d,J＝8.7Hz,2H),7.95(dd,J＝19.8,11.2Hz,3H),7.61(t,J＝7.4Hz,1H),7.48(t,J＝7.7Hz,2H),7.29(d,J＝14.9Hz,1H)； 13 C NMR(126MHz,CDCl 3 )δ187.05,151.10,144.42,140.54,135.71,135.19,134.83,129.76,129.24,129.06,124.85。
Example 34
In this example, (E) -3- (2-chlorobenzenesulfonyl) -1-phenyl-2-propen-1-one ((E) -3- ((2-chlorophenylyl) sulfonyl) -1-phenylprop-2-en-1-one) was prepared, which has the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6mg, 0.4 mmol), 1-phenyl-2-propyn-1-one (26.0mg, 0.2mmol) and sodium 2-chlorophenylene sulfonate (99.3mg, 0.5 mmol) were weighed in a 10mLSchlen tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then, the mixture was sealed and reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system through a sand core funnel with silica gel, washing filter residues with 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating the residues through column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the target product was obtained as a white solid in 77% yield; rf =0.5 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl 3 )δ8.21(d,J＝7.2Hz,1H),8.03(dd,J＝24.1,11.0Hz,3H),7.67-7.50(m,7H)； 13 C NMR(126MHz,CDCl 3 )δ187.57,140.16,136.33,135.96,135.91,135.52,134.58,133.28,132.16,131.43,129.15,129.05,127.78。
Example 35
In this example, (E) -3- (3-chlorobenzenesulfonyl) -1-phenyl-2-propen-1-one ((E) -3- ((3-chlorophenylyl) sulfonyl) -1-phenylprop-2-en-1-one) was prepared, which has the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6mg, 0.4 mmol), 1-phenyl-2-propyn-1-one (26.0mg, 0.2mmol) and sodium 3-chlorophenylene sulfonate (99.3mg, 0.5 mmol) were weighed in a 10mLSchlen tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then, the mixture was sealed and reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system by a sand core funnel with silica gel, washing filter residues by 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating by column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the target product was obtained as a yellow solid in 81% yield; rf =0.4 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl 3 )δ7.99-7.93(m,4H),7.85(d,J＝7.9Hz,1H),7.66(t,J＝8.0Hz,2H),7.56-7.52(m,3H),7.35(d,J＝14.9Hz,1H)； 13 C NMR(126MHz,CDCl 3 )δ187.40,141.35,140.51,135.91,134.59,134.50,134.00,130.99,129.14,129.02,128.29,126.41。
Example 36
In this example, (E) -3- (2-naphthalenesulfonyl) -1-phenyl-2-propen-1-one ((E) -3- (naphtalen-2-ylsulfonyl) -1-phenylprop-2-en-1-one) was prepared, which has the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6mg, 0.4 mmol), 1-phenyl-2-propyn-1-one (26.0mg, 0.2mmol) and sodium 2-naphthalenesulfinate (107.0mg, 0.5 mmol) were weighed in a 10mLSchlenk tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then, the mixture was sealed and reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system by a sand core funnel with silica gel, washing filter residues by 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating by column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the target product was obtained as a yellow solid in 87% yield; rf =0.3 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl 3 )δ8.57(s,1H),8.03-7.97(m,5H),7.94(d,J＝8.1Hz,1H),7.88(dd,J＝8.7,1.7Hz,1H),7.70(dd,J＝11.1,4.0Hz,1H),7.65(t,J＝7.4Hz,2H),7.53(t,J＝7.8Hz,2H),7.43(d,J＝14.9Hz,1H)； 13 C NMR(126MHz,CDCl 3 )δ187.71,142.05,136.03,135.58,135.39,134.50,133.14,132.31,130.44,130.08,129.78,129.56,129.11,129.01,128.09,127.98,122.56。
Example 37
In this example, (E) -3- (cyclopropylsulfonyl) -1-phenyl-2-propen-1-one ((E) -3- (cyclopropysulfonyl) -1-phenylprop-2-en-1-one) was prepared, having the formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6mg, 0.4 mmol), 1-phenyl-2-propyn-1-one (26.0mg, 0.2mmol) and sodium cyclopropanesulfinate (64.0mg, 0.5 mmol) were weighed in a 10mLSchlen tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then, the mixture was sealed and reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system by a sand core funnel with silica gel, washing filter residues by 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating by column chromatography to obtain a pyridine product; the column chromatography separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the target product was obtained as a white solid in 75% yield; rf =0.4 (PE: EA = 5:1).
1 H NMR(500MHz,CDCl 3 )δ8.21(d,J＝14.0Hz,2H),7.81(s,2H),7.57(s,1H),7.49(s,2H),1.72(s,2H),1.02(s,2H),0.68(s,1H)； 13 C NMR(125MHz,CDCl 3 )δ186.56,150.36,137.81,133.34,128.80,128.76,122.33,32.68,15.50。
Example 38
In this example, (E) -3- (2-chloroethylsulfonyl) -1-phenyl-2-propen-1-one ((E) -3- ((2-chloroethyl) sulfonyl) -1-phenylprop-2-en-1-one) was prepared, which had the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6mg, 0.4 mmol), 1-phenyl-2-propyn-1-one (26.0mg, 0.2mmol) and sodium 2-chloroethane-1-sulfinate (75.0mg, 0.5 mmol) were weighed in a 10mL Schlenk tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then, the mixture was sealed and reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system through a sand core funnel with silica gel, washing filter residues with 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating the residues through column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the target product was obtained as a yellow solid in 76% yield; rf =0.4 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl 3 )δ8.42-7.62(m,2H),7.55(s,3H),7.47(s,2H),4.02(s,2H),3.68(s,2H)； 13 C NMR(125MHz,CDCl 3 )δ186.56,140.81,137.81,133.34,128.80,128.76,123.12,47.89,39.33。
Example 39
In this example, (E) -7,7-dimethyl-1- (((3-oxo-3-phenylprop-1-en-1-yl) sulfonyl) methyl) bicyclo [2.2.1] heptan-2-one was prepared as follows:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6mg, 0.4 mmol), 1-phenyl-2-propyn-1-one (26.0mg, 0.2mmol) and (7,7-dimethyl-2-oxobicyclo [2.2.1] hept-1-yl) sodium methanesulfinate (119.1mg, 0.5 mmol) were weighed into a 10mLSchlen tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then, after sealing, it was reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system by a sand core funnel with silica gel, washing filter residues by 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating by column chromatography to obtain a pyridine product; the column chromatography separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the target product was obtained as a white solid in 74% yield; rf =0.3 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl 3 )δ8.21(d,J＝7.4Hz,2H),7.81(s,2H),7.57(s,1H),7.49(s,2H),3.57(d,J＝125.0Hz,2H),2.23(s,1H),2.09(s,1H),1.88(d,J＝105.0Hz,2H),1.75-1.73(m,2H),1.66(s,4H),1.52(s,4H),1.41(s,3H),0.99(s,3H)； 13 C NMR(125MHz,CDCl 3 )δ215.74,186.56,142.97,137.81,133.34,128.80,128.76,122.86,61.50,55.70,48.62,44.12,42.94,29.36,28.28,20.11。
Example 40
In this example, 1-phenyl-3- (phenylsulfonyl) propan-1-one (1-phenyl-3- (phenylsulfonyl) propan-1-one) was prepared, having the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6 mg,0.4 mmol), 1-phenyl-2-propenyl-1-one (26.0 mg, 0.2mmol) and sodium benzenesulfinate (82.1mg, 0.5 mmol) were weighed into a 10mLSchlen tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then sealed and reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system by a sand core funnel with silica gel, washing filter residues by 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating by column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the target product was obtained as a white solid in 84% yield; rf =0.5 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl 3 )δ7.99-7.95(m,2H),7.93-7.92(m,2H),7.68(dd,J＝10.6,4.3Hz,1H),7.61-7.58(m,3H),7.48(t,J＝7.7Hz,2H),3.59-3.56(m,2H),3.53-3.49(m,2H)； 13 C NMR(126MHz,CDCl 3 )δ195.46,139.07,135.81,133.98,133.84,129.46,128.83,128.09,128.02,51.05,31.39。
The target product was analyzed by nmr hydrogen spectroscopy, and the results are shown in fig. 3. FIG. 3 is a NMR chart of a target product prepared in example 40 of the present invention.
The target product was subjected to nmr analysis, and the results are shown in fig. 4. FIG. 4 is a NMR carbon spectrum of a target product prepared in example 40 of the present invention.
EXAMPLE 41
In this example, 1- (4-methoxyphenyl) -3- (phenylsulfonyl) propan-1-one (1- (4-methoxyphenyl) -3- (phenylsulfonyl) propan-1-one) was prepared, having the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6mg, 0.4 mmol), 1- (4-methoxy) phenyl-2-propenyl-1-one (32.4 mg, 0.2mmol) and sodium benzenesulfonate (82.1mg, 0.5 mmol) were weighed into a 10mLSchlen tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then sealed and reacted at 30 ℃ for 48h. Filtering the reacted mixed system by a sand core funnel with silica gel, washing filter residues by 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating by column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the obtained target product is a white solid with 98% yield; rf =0.2 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl 3 )δ7.95(d,J＝7.4Hz,2H),7.90(d,J＝7.3Hz,2H),7.67(t,J＝7.2Hz,1H),7.58(t,J＝7.1Hz,2H),6.93(d,J＝7.3Hz,2H),3.87(s,3H),3.57-3.54(m,2H),3.46-3.43(m,2H)； 13 C NMR(126MHz,CDCl 3 )δ193.88,164.01,139.08,133.95,130.42,129.44,128.87,128.01,113.96,55.57,51.17,30.95； 13 C NMR(126MHz,CDCl 3 )δ193.88,164.01,139.08,133.95,130.42,129.44,128.87,128.01,113.96,55.57,51.17,30.95。
Example 42
In this example, 1- ([ 1,1'-biphenyl ] -4-yl) -3- (phenylsulfonyl) propan-1-one (1- ([ 1,1' -biphenyl ] -4-yl) -3- (phenylsulfonyl) propan-1-one) was prepared, which has the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6 mg,0.4 mmol), 1- (4-phenyl) phenyl-2-propenyl-1-one (41.7 mg, 0.2mmol) and sodium benzenesulfinate (82.1mg, 0.5 mmol) were weighed into a 10mLSchlenk tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then sealed and reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system by a sand core funnel with silica gel, washing filter residues by 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating by column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the target product was obtained as a white solid in 88% yield; rf =0.3 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl 3 )δ7.92-7.89(m,3H),7.62-7.58(m,3H),7.55-7.50(m,3H),7.40(t,J＝7.4Hz,2H),7.34(d,J＝7.3Hz,1H),3.51-3.45(m,4H)； 13 C NMR(126MHz,CDCl 3 )δ193.99,145.45,138.54,138.07,133.45,132.94,128.43,127.99,127.66,127.42,126.99,126.38,126.25,50.05,30.36。
Example 43
In this example, 1- (4-fluorophenyl) -3- (benzenesulfonyl) propan-1-one (1- (4-fluorophenylyl) -3- (phenylsulfonyl) propan-1-one) was prepared, which had the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6 mg,0.4 mmol), 1- (4-fluorophenyl) -2-propenyl-1-one (41.7 mg,0.2 mmol) and sodium benzenesulfinate (82.1mg, 0.5 mmol) were weighed in a 10mL Schlenk tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then, after sealing, reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system by a sand core funnel with silica gel, washing filter residues by 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating by column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the obtained target product is a white solid with a yield of 97%; rf =0.3 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl 3 )δ7.97-7.95(m,4H),7.68(t,J＝7.4Hz,1H),7.59(t,J＝7.6Hz,2H),7.14(t,J＝8.5Hz,2H),3.56(d,J＝7.3Hz,2H),3.48(d,J＝7.2Hz,2H)； 13 C NMR(126MHz,CDCl 3 )δ193.89,166.11(d,J＝256.3Hz),139.02,134.02,132.27(d,J＝2.8Hz),130.81(d,J＝9.3Hz),129.48,128.00,116.09,115.91,50.97,31.27。
Example 44
In this example, 1- (4-chlorophenyl) -3- (benzenesulfonyl) propan-1-one (1- (4-chlorophenyl) -3- (phenylsulfonyl) propan-1-one) was prepared, having the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6 mg,0.4 mmol), 1- (4-chlorophenyl) -2-propenyl-1-one (33.3 mg,0.2 mmol) and sodium benzenesulfinate (82.1mg, 0.5 mmol) were weighed into a 10mLSchlen tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then, after sealing, reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system by a sand core funnel with silica gel, washing filter residues by 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating by column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the target product was obtained as a white solid in 87% yield; rf =0.4 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl 3 )δ7.95(d,J＝7.5Hz,2H),7.87(d,J＝8.3Hz,2H),7.68(t,J＝7.1Hz,1H),7.59(t,J＝7.5Hz,2H),7.45(d,J＝8.2Hz,2H),3.57-3.55(m,2H),3.49-3.46(m,2H)； 13 C NMR(126MHz,CDCl 3 )δ194.31,140.37,138.99,134.10,134.05,131.55,129.50,129.18,128.00,50.92,31.34。
Example 45
In this example, 4- (3- (phenylsulfonyl) propionyl) benzonitrile (4- (3- (phenylsulfonyl) propanoyl) benzonitril) is prepared, which has the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6mg, 0.4 mmol), 1- (4-cyano) -2-propenyl-1-one (31.4 mg, 0.2mmol) and sodium benzenesulfinate (82.1mg, 0.5 mmol) were weighed into a 10mLSchlen tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then sealed and reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system by a sand core funnel with silica gel, washing filter residues by 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating by column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the obtained target product was a white solid with a yield of 95%; rf =0.4 (PE: EA = 2:1).
1 H NMR(500MHz,CDCl 3 )δ7.95(d,J＝8.3Hz,2H),7.87(d,J＝7.8Hz,2H),7.71(d,J＝8.2Hz,2H),7.62(t,J＝7.4Hz,1H),7.52(t,J＝7.7Hz,2H),3.49(d,J＝6.5Hz,2H),3.45(d,J＝7.0Hz,2H)； 13 C NMR(126MHz,CDCl 3 )δ193.32,137.89,137.65,133.12,131.68,128.52,127.51,126.95,116.67,116.03,49.70,30.69。
Example 46
In this example, 1- (4-nitrophenyl) -3- (phenylsulfonyl) propan-1-one (1- (4-nitrophenyl) -3- (phenylsulfonyl) propan-1-one) was prepared, which has the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6 mg,0.4 mmol), 1- (4-nitro) -2-propenyl-1-one (35.4 mg,0.2 mmol) and sodium benzenesulfinate (82.1mg, 0.5 mmol) were weighed into a 10mLSchlen tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then sealed and reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system by a sand core funnel with silica gel, washing filter residues by 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating by column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the target product was obtained as a yellow solid in 75% yield; rf =0.4 (PE: EA = 2:1).
1 H NMR(500MHz,CDCl 3 )δ8.36(d,J＝15.0Hz,4H),7.84(d,J＝60.0Hz,4H),7.76(s,2H),7.66(s,2H),3.36(d,J＝14.1Hz,2H)； 13 C NMR(125MHz,CDCl 3 )δ197.30,151.22,142.66,139.72,132.94,129.33,129.22,128.94,124.75,50.53,35.28。
Example 47
In this example, 1- (phenylsulfonyl) octan-3-one (1- (phenylsulfonyl) octan-3-one) was prepared, having the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6 mg,0.4 mmol), 1-octen-3-one (25.2mg, 0.2mmol) and sodium benzenesulfinate (82.1mg, 0.5 mmol) were weighed into a 10mLSchlen tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then sealed and reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system by a sand core funnel with silica gel, washing filter residues by 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating by column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the obtained target product is a yellow solid with 80% yield; rf =0.4 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl 3 )δ7.84(d,J＝60.0Hz,1H),7.77(d,J＝6.6Hz,1H),7.66(s,1H),3.46(s,1H),3.13(s,2H),2.40(s,2H),1.53(s,2H),1.33(s,2H),1.25(s,4H),0.89(s,3H)； 13 C NMR(125MHz,CDCl 3 )δ209.10,139.72,132.94,129.33,129.22,50.16,42.75,34.08,30.91,25.53,23.16,14.00。
Example 48
In this example, 1-phenyl-3-tosylpropan-1-one (1-phenyl-3-tosylpropan-1-one) was prepared, which has the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6mg, 0.4 mmol), 1-phenyl-2-propenyl-1-one (26.0mg, 0.2mmol) and sodium 4-methylbenzenesulfinate (89.1mg, 0.5 mmol) were weighed into a 10mLSchlenk tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then, the mixture was sealed and reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system by a sand core funnel with silica gel, washing filter residues by 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating by column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the obtained target product is a yellow solid with a yield of 95%; rf =0.4 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl 3 )δ7.92(d,J＝7.5Hz,2H),7.83(d,J＝8.1Hz,2H),7.59(t,J＝7.3Hz,1H),7.47(t,J＝7.6Hz,2H),7.37(d,J＝7.9Hz,2H),3.54(d,J＝7.4Hz,2H),3.49(d,J＝7.6Hz,2H),2.45(s,3H)； 13 C NMR(126MHz,CDCl 3 )δ195.58,145.04,136.01,135.81,133.82,130.08,128.82,128.09,128.05,51.11,31.53,21.70。
Example 49
In this example, 2-methyl-1-phenyl-3- (phenylsulfonyl) propan-1-one (2-methyl-1-phenyl-3- (phenylsulfonyl) propan-1-one) was prepared, having the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6 mg,0.4 mmol), 2-methyl-1-phenyl-2-propenyl-1-one (29.2mg, 0.2mmol) and sodium benzenesulfinate (82.1mg, 0.5 mmol) were weighed into a 10mLSchlenk tube with magnetons, 3.0mL of mesitylene was added with a pipette, and then sealed and reacted at 30 ℃ for 48 hours. Filtering the reacted mixed system by a sand core funnel with silica gel, washing filter residues by 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating by column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the obtained target product is a yellow solid with a yield of 60%; rf =0.4 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl 3 )δ8.01(d,J＝3.0Hz,2H),7.90-7.85(m,2H),7.81-7.71(m,1H),7.69-7.59(m,3H),7.56–7.45(m,2H),4.03(qt,J＝12.9,9.8Hz,1H),3.66(dd,J＝24.7,9.7Hz,1H),3.41(dd,J＝24.7,9.9Hz,1H),1.21(d,J＝12.7Hz,3H)； 13 C NMR(125MHz,CDCl 3 )δ199.57,139.96,136.96,132.86,132.65,129.47,129.15,128.72,128.51,57.49,38.97,15.59。
Example 50
In this example, 3-trifluoromethyl-1-phenyl-3- (phenylsulfonyl) propan-1-one (4,4,4-triflo-1-phenyl-3- (phenylsulfonyl) butan-1-one) was prepared having the following structural formula:
the preparation method comprises the following steps:
4-chlorobenzoic acid (62.6 mg,0.4 mmol), (E) -4,4,4-trifluoro-1-phenylbutan-2-propen-1-one (40mg, 0.2mmol) and sodium benzenesulfinate (82.1mg, 0.5 mmol) were weighed into a 10mL Schlenk tube with magnetons, 3.0mL mesitylene was added with a pipette and then reacted at 30 ℃ for 48h after sealing. Filtering the reacted mixed system through a sand core funnel with silica gel, washing filter residues with 20mL ethyl acetate, concentrating the obtained filtrate and washing liquid under reduced pressure to obtain residues, and purifying and separating the residues through column chromatography to obtain a pyridine product; the column chromatographic separation adopts 200-300 meshes of silica gel, and the mobile phase adopts petroleum ether: ethyl acetate in a volume ratio of 4:1. the obtained target product is a yellow solid with a yield of 55%; rf =0.4 (PE: EA = 4:1).
1 H NMR(500MHz,CDCl 3 )δ7.99-7.85(m,1H),7.83-7.72(m,1H),7.71-7.56(m,1H),7.51-7.39(m,1H),4.33(qt,J＝17.9,14.3Hz,1H),3.54(dd,J＝24.7,14.3Hz,1H),3.33(dd,J＝24.8,14.4Hz,1H)； 13 C NMR(125MHz,CDCl 3 )δ194.15,139.82,136.83,133.16,132.89,130.27,129.40,128.88,128.78,122.76,36.40； 19 F NMR(472MHz,CDCl 3 )δ-45.50。
The above description of the embodiments is only intended to facilitate the understanding of the method of the invention and its core idea. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.
Claims (12)
1. A preparation method of a gamma-ketone sulfone compound comprises the following steps:
mixing an alkynone compound with a structure shown in a formula I, a compound with a structure shown in a formula II, an acid and a solvent, and reacting to obtain a gamma-ketosulfone compound with a structure shown in a formula III;
wherein R is 1 Selected from hydrogen, C1-C10 straight-chain alkyl, C1-C10 branched-chain alkyl, C3-C10 cyclic alkyl, substituted or unsubstituted C6-C20 aryl, and substituted or unsubstituted heterocyclic group containing nitrogen, oxygen and sulfur atoms; wherein, the substituent of the aryl or heterocyclic group is selected from C1-C10 straight-chain alkyl, C1-C10 branched-chain alkyl, C3-C10 cyclic alkyl, halogen, nitro or amino;
R 2 selected from C1-C10 straight-chain alkyl, C1-C10 branched-chain alkyl, C3-C10 cyclic alkyl, trifluoromethyl, substituted or unsubstituted C6-C20 aryl, and substituted or unsubstituted heterocyclic groups containing nitrogen, oxygen and sulfur atoms; wherein, the substituent of the aryl or heterocyclic group is selected from C1-C10 straight-chain alkyl, C1-C10 branched-chain alkyl, C3-C10 cyclic alkyl, halogen, nitro or amino;
R 4 selected from hydrogen, C1-C10 straight-chain alkyl, C1-C10 branched-chain alkyl, C3-C10 cyclic alkyl, substituted or unsubstituted C6-C20 aryl, trifluoromethyl, and substituted or unsubstituted heterocyclic group containing nitrogen, oxygen and sulfur atoms; wherein, the substituent of the aryl or heterocyclic group is selected from C1-C10 straight-chain alkyl, C1-C10 branched-chain alkyl, C3-C10 cyclic alkyl, halogen, nitro or amino.
2. The method of claim 1, wherein R is 1 Selected from hydrogen, halogen-substituted phenyl, methyl-substituted phenyl, methoxy-substituted phenyl, mesylSubstituted phenyl, biphenyl, dimethylamino-substituted phenyl, trifluoromethyl-substituted phenyl, nitro-substituted phenyl, anthracenyl, indolyl, benzyl or substituted quinolinyl;
R 2 selected from phenyl, methyl-substituted phenyl, tert-butyl-substituted phenyl, methoxy-substituted phenyl, trifluoromethoxy-substituted phenyl, mesityl, halogen-substituted phenyl, trifluoromethyl-substituted phenyl, nitro-substituted phenyl, naphthyl, cyclopropylalkyl, chloroethyl or a cycloalkyl group containing a keto group;
R 4 selected from hydrogen, methine or phenyl.
3. The method according to claim 1, wherein R is 1 One selected from the formulas R1-1 to R1-18;
said R is 2 One selected from the formulas R2-1 to R2-18;
4. the preparation method according to claim 1, wherein the γ -ketosulfone compound having the structure represented by formula iii is selected from one of formulae iii-1 to iii-37;
5. the method of claim 1, wherein the acid comprises at least one of acetic acid, formic acid, hydrochloric acid, nitric acid, benzoic acid, p-toluic acid, 4-acetylbenzoic acid, 4-fluorobenzoic acid, 4-chlorobenzoic acid, bromobenzoic acid, 4-nitrobenzoic acid, 2-naphthoic acid, and 2-nitrobenzoic acid;
the solvent comprises at least one of dimethyl sulfoxide, 1,4-dioxane, toluene, methanol, o-xylene, m-xylene, p-xylene, trifluorotoluene and mesitylene;
the molar ratio of the alkynone compound with the structure shown in the formula I to the compound with the structure shown in the formula II is 1:1 to 3;
the molar ratio of the alkynone compound with the structure shown in the formula I to the acid is 1:0.5 to 3;
the dosage ratio of the alkynone compound with the structure shown in the formula I to the solvent is 0.02-0.07 mol:1L of the total amount of the active ingredients.
6. The preparation method according to claim 1, wherein the reaction temperature is 25-80 ℃ and the reaction time is 24-48 h;
after the reaction, the method further comprises the following steps:
filtering the product solution after the reaction, washing filter residues with ethyl acetate, and carrying out reduced pressure concentration and column chromatographic separation on the obtained filtrate and washing liquid to obtain a gamma-ketosulfone compound with a structure shown in a formula III;
the column chromatographic separation selects 200-300 mesh silica gel, the mobile phase selects petroleum ether and ethyl acetate, and the volume ratio is 3-5: 1.
7. a preparation method of a gamma-ketone sulfone compound comprises the following steps:
mixing an ketene compound with a structure shown in a formula IV, a compound with a structure shown in a formula II, an acid and a solvent, and reacting to obtain a gamma-ketosulfone compound with a structure shown in a formula V;
wherein R is 1 Selected from hydrogen, C1-C10 straight-chain alkyl, C1-C10 branched-chain alkyl, C3-C10 cyclic alkyl, substituted or unsubstituted C6-C20 aryl, and substituted or unsubstituted heterocyclic group containing nitrogen, oxygen and sulfur atoms; wherein, the substituent of the aryl or heterocyclic group is selected from C1-C10 straight-chain alkyl, C1-C10 branched-chain alkyl, C3-C10 cyclic alkyl, halogen, nitro or amino;
R 2 selected from C1-C10 straight-chain alkyl, C1-C10 branched-chain alkyl, C3-C10 cyclic alkyl, trifluoromethyl, substituted or unsubstituted C6-C20 aryl, and substituted or unsubstituted heterocyclic groups containing nitrogen, oxygen and sulfur atoms; wherein, the substituent of the aryl or heterocyclic group is selected from C1-C10 straight-chain alkyl, C1-C10 branched-chain alkyl, C3-C10 cyclic alkyl, halogen, nitro or amino;
R 3 selected from hydrogen, C1-C10 straight-chain alkyl, C1-C10 branched-chain alkyl and C3-C10 cyclic alkyl;
R 4 selected from hydrogen, C1-C10 straight-chain alkyl, C1-C10 branched-chain alkyl, C3-C10 cyclic alkyl, substituted or unsubstituted C6-C20 aryl, trifluoromethyl, and substituted or unsubstituted heterocyclic groups containing nitrogen, oxygen and sulfur atoms; wherein, the substituent of the aryl or heterocyclic group is selected from C1-C10 straight-chain alkyl, C1-C10 branched-chain alkyl, C3-C10 cyclic alkyl, halogen, nitro or amino.
8. The method according to claim 7, wherein R is 1 Selected from hydrogen, phenyl, methoxy substituted phenyl, biphenyl, halogen substituted phenyl, cyano substituted phenyl, nitro substituted phenyl or pentyl;
R 2 selected from phenyl or methyl substituted phenyl;
R 3 selected from hydrogen or methyl;
R 4 selected from hydrogen or trifluoromethyl.
9. The method of claim 7, wherein R is 1 One selected from the group consisting of r1-1 to r 1-8;
the R is 2 One selected from the group consisting of r2-1 to r 2-2;
10. the preparation method according to claim 7, wherein the γ -ketosulfone compound having the structure represented by formula v is selected from one of formula v-1 to formula v-11;
11. the method of claim 7, wherein the acid comprises at least one of acetic acid, formic acid, hydrochloric acid, nitric acid, benzoic acid, p-toluic acid, 4-acetylbenzoic acid, 4-fluorobenzoic acid, 4-chlorobenzoic acid, bromobenzoic acid, 4-nitrobenzoic acid, 2-naphthoic acid, and 2-nitrobenzoic acid;
the solvent comprises at least one of dimethyl sulfoxide, 1,4-dioxane, toluene, methanol, o-xylene, m-xylene, p-xylene, trifluorotoluene and mesitylene;
the mol ratio of the ketene compound with the structure shown in the formula IV to the compound with the structure shown in the formula II is 1:1 to 3;
the mol ratio of the ketene compound with the structure shown in the formula IV to the acid is 1:0.5 to 3;
the dosage ratio of the ketene compound with the structure shown in the formula IV to the solvent is 0.02-0.1 mol:1L of the total amount of the active ingredients.
12. The preparation method of claim 7, wherein the reaction temperature is 25-80 ℃ and the reaction time is 12-48 h;
after the reaction, the method further comprises the following steps:
filtering the product solution after the reaction, washing filter residues with ethyl acetate, and carrying out reduced pressure concentration and column chromatographic separation on the obtained filtrate and washing liquid to obtain a gamma-ketosulfone compound with a structure shown in a formula III;
the column chromatographic separation selects 200-300 mesh silica gel, the mobile phase selects petroleum ether and ethyl acetate, and the volume ratio is 3-5: 1.
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| CN105906537A (en) * | 2016-04-27 | 2016-08-31 | 湖南科技学院 | One-pot synthesis method of (Z)-type sulfonyl olefine acid ester compound |
| CN106083669A (en) * | 2016-06-24 | 2016-11-09 | 湖南大学 | A kind of method being prepared β chlorine alkene sulfone compound by sulfinate and alkynes |
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| CN116162052A (en) * | 2022-12-13 | 2023-05-26 | 三峡大学 | Preparation method of 2-benzylidene indoline-3-ketone compound |
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