CN111170905A - 一种磺酰胺类化合物的合成方法 - Google Patents
一种磺酰胺类化合物的合成方法 Download PDFInfo
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- CN111170905A CN111170905A CN201911388271.8A CN201911388271A CN111170905A CN 111170905 A CN111170905 A CN 111170905A CN 201911388271 A CN201911388271 A CN 201911388271A CN 111170905 A CN111170905 A CN 111170905A
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- Prior art keywords
- electron
- compound
- copper
- group
- heterocyclic ring
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Links
- -1 sulfonamide compound Chemical class 0.000 title claims abstract description 53
- 229940124530 sulfonamide Drugs 0.000 title claims abstract description 23
- 238000010189 synthetic method Methods 0.000 title description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims abstract description 33
- 229910052802 copper Inorganic materials 0.000 claims abstract description 18
- 239000010949 copper Substances 0.000 claims abstract description 18
- 150000001875 compounds Chemical class 0.000 claims abstract description 17
- RWPGFSMJFRPDDP-UHFFFAOYSA-L potassium metabisulfite Chemical compound [K+].[K+].[O-]S(=O)S([O-])(=O)=O RWPGFSMJFRPDDP-UHFFFAOYSA-L 0.000 claims abstract description 17
- 229940043349 potassium metabisulfite Drugs 0.000 claims abstract description 17
- 235000010263 potassium metabisulphite Nutrition 0.000 claims abstract description 17
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims abstract description 16
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims abstract description 15
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims abstract description 15
- 238000000034 method Methods 0.000 claims abstract description 13
- 230000009471 action Effects 0.000 claims abstract description 12
- 238000010438 heat treatment Methods 0.000 claims abstract description 11
- 239000003054 catalyst Substances 0.000 claims abstract description 10
- DOUHZFSGSXMPIE-UHFFFAOYSA-N hydroxidooxidosulfur(.) Chemical compound [O]SO DOUHZFSGSXMPIE-UHFFFAOYSA-N 0.000 claims abstract description 9
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000002360 preparation method Methods 0.000 claims abstract description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 51
- 238000006243 chemical reaction Methods 0.000 claims description 42
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 20
- 125000000623 heterocyclic group Chemical group 0.000 claims description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 16
- 239000003446 ligand Substances 0.000 claims description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- 229910052786 argon Inorganic materials 0.000 claims description 10
- 239000003638 chemical reducing agent Substances 0.000 claims description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 9
- 239000004327 boric acid Substances 0.000 claims description 9
- 238000004440 column chromatography Methods 0.000 claims description 9
- 238000012544 monitoring process Methods 0.000 claims description 9
- 239000012074 organic phase Substances 0.000 claims description 9
- 239000012071 phase Substances 0.000 claims description 9
- 238000000926 separation method Methods 0.000 claims description 9
- 239000000243 solution Substances 0.000 claims description 9
- 238000001308 synthesis method Methods 0.000 claims description 9
- 238000012360 testing method Methods 0.000 claims description 9
- 238000009423 ventilation Methods 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 8
- 125000002252 acyl group Chemical group 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000003277 amino group Chemical group 0.000 claims description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- 239000000460 chlorine Chemical group 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 230000002950 deficient Effects 0.000 claims description 8
- 239000011737 fluorine Substances 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- 150000002828 nitro derivatives Chemical class 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 239000003208 petroleum Substances 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 7
- 150000001543 aryl boronic acids Chemical class 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 239000011259 mixed solution Substances 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 5
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 claims description 4
- 125000006575 electron-withdrawing group Chemical group 0.000 claims description 4
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 4
- 230000002194 synthesizing effect Effects 0.000 claims description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 125000004185 ester group Chemical group 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 3
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 claims description 2
- DWYFDOGPFCQTIE-UHFFFAOYSA-N 1,2,2-trimethylpyrrolidin-3-one Chemical compound CN1CCC(=O)C1(C)C DWYFDOGPFCQTIE-UHFFFAOYSA-N 0.000 claims description 2
- QFMZQPDHXULLKC-UHFFFAOYSA-N 1,2-bis(diphenylphosphino)ethane Chemical class C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 QFMZQPDHXULLKC-UHFFFAOYSA-N 0.000 claims description 2
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical class N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 claims description 2
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 2
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 claims description 2
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 2
- SBTSVTLGWRLWOD-UHFFFAOYSA-L copper(ii) triflate Chemical compound [Cu+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F SBTSVTLGWRLWOD-UHFFFAOYSA-L 0.000 claims description 2
- 229940045803 cuprous chloride Drugs 0.000 claims description 2
- UVJHQYIOXKWHFD-UHFFFAOYSA-N cyclohexa-1,4-diene Chemical compound C1C=CCC=C1 UVJHQYIOXKWHFD-UHFFFAOYSA-N 0.000 claims description 2
- UTGAVWVWCKHFRU-UHFFFAOYSA-N dimethyl 2,6-dimethylpyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=CC(C(=O)OC)=C(C)N=C1C UTGAVWVWCKHFRU-UHFFFAOYSA-N 0.000 claims description 2
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 claims description 2
- 235000010265 sodium sulphite Nutrition 0.000 claims description 2
- 238000003756 stirring Methods 0.000 claims description 2
- 150000003456 sulfonamides Chemical class 0.000 claims description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 1
- 239000011630 iodine Chemical group 0.000 claims 1
- 229910052740 iodine Inorganic materials 0.000 claims 1
- 238000002156 mixing Methods 0.000 claims 1
- 150000005041 phenanthrolines Chemical class 0.000 claims 1
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 abstract description 12
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 abstract description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 abstract description 9
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 abstract description 8
- 230000009467 reduction Effects 0.000 abstract description 6
- 238000006555 catalytic reaction Methods 0.000 abstract description 5
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 abstract description 5
- 239000002904 solvent Substances 0.000 abstract 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 abstract 1
- 150000004982 aromatic amines Chemical class 0.000 abstract 1
- 239000003153 chemical reaction reagent Substances 0.000 abstract 1
- 230000000536 complexating effect Effects 0.000 abstract 1
- 125000000524 functional group Chemical group 0.000 abstract 1
- 229910052708 sodium Inorganic materials 0.000 abstract 1
- 239000011734 sodium Substances 0.000 abstract 1
- 239000000758 substrate Substances 0.000 abstract 1
- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 12
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 238000012512 characterization method Methods 0.000 description 7
- CAYQIZIAYYNFCS-UHFFFAOYSA-N (4-chlorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Cl)C=C1 CAYQIZIAYYNFCS-UHFFFAOYSA-N 0.000 description 5
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 5
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 4
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 238000006713 insertion reaction Methods 0.000 description 2
- WFKAJVHLWXSISD-UHFFFAOYSA-N isobutyramide Chemical compound CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 2
- 150000003871 sulfonates Chemical class 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- SDEAGACSNFSZCU-UHFFFAOYSA-N (3-chlorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(Cl)=C1 SDEAGACSNFSZCU-UHFFFAOYSA-N 0.000 description 1
- COLPLFZHPXIFCQ-UHFFFAOYSA-N 1,4-dihydropyridine-3,5-dicarboxylic acid Chemical compound OC(=O)C1=CNC=C(C(O)=O)C1 COLPLFZHPXIFCQ-UHFFFAOYSA-N 0.000 description 1
- SCCCFNJTCDSLCY-UHFFFAOYSA-N 1-iodo-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(I)C=C1 SCCCFNJTCDSLCY-UHFFFAOYSA-N 0.000 description 1
- CZGCEKJOLUNIFY-UHFFFAOYSA-N 4-Chloronitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=C1 CZGCEKJOLUNIFY-UHFFFAOYSA-N 0.000 description 1
- CQHCWIOJHKGUPA-UHFFFAOYSA-N 4-chloro-N-(4-formylphenyl)benzenesulfonamide Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)NC1=CC=C(C=O)C=C1 CQHCWIOJHKGUPA-UHFFFAOYSA-N 0.000 description 1
- CALNUDRLRJURKB-UHFFFAOYSA-N 4-chloro-n-(4-chlorophenyl)benzenesulfonamide Chemical compound C1=CC(Cl)=CC=C1NS(=O)(=O)C1=CC=C(Cl)C=C1 CALNUDRLRJURKB-UHFFFAOYSA-N 0.000 description 1
- NSULXXCIZRGXLS-UHFFFAOYSA-N 4-chloro-n-(4-iodophenyl)benzenesulfonamide Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)NC1=CC=C(I)C=C1 NSULXXCIZRGXLS-UHFFFAOYSA-N 0.000 description 1
- 125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 description 1
- BXRFQSNOROATLV-UHFFFAOYSA-N 4-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=C(C=O)C=C1 BXRFQSNOROATLV-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- ZXRQXDKYKXXJAE-UHFFFAOYSA-N C1(=CC=CC=C1)NS(=O)(=O)C1=CC2=CC=CC=C2C=C1.C1(=CC=CC=C1)NS(=O)(=O)C1=CC2=CC=CC=C2C=C1 Chemical compound C1(=CC=CC=C1)NS(=O)(=O)C1=CC2=CC=CC=C2C=C1.C1(=CC=CC=C1)NS(=O)(=O)C1=CC2=CC=CC=C2C=C1 ZXRQXDKYKXXJAE-UHFFFAOYSA-N 0.000 description 1
- KJEBULYHNRNJTE-DHZHZOJOSA-N Cinalong Chemical compound COCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC\C=C\C=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 KJEBULYHNRNJTE-DHZHZOJOSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 1
- HJLSLZFTEKNLFI-UHFFFAOYSA-N Tinidazole Chemical compound CCS(=O)(=O)CCN1C(C)=NC=C1[N+]([O-])=O HJLSLZFTEKNLFI-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000013064 chemical raw material Substances 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 229960003020 cilnidipine Drugs 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 1
- 229960002074 flutamide Drugs 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229940047889 isobutyramide Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- VGGNVBNNVSIGKG-UHFFFAOYSA-N n,n,2-trimethylaziridine-1-carboxamide Chemical compound CC1CN1C(=O)N(C)C VGGNVBNNVSIGKG-UHFFFAOYSA-N 0.000 description 1
- KPTRDYONBVUWPD-UHFFFAOYSA-N naphthalen-2-ylboronic acid Chemical compound C1=CC=CC2=CC(B(O)O)=CC=C21 KPTRDYONBVUWPD-UHFFFAOYSA-N 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229960005053 tinidazole Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/21—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen directly attached to ring carbon atoms
- C07D211/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/88—Nitrogen atoms, e.g. allantoin
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
本发明属有机化学技术领域,具体为磺酰胺类化合物的制备方法。此类化合物的结构经1H NMR、13C NMR表征并得以确认。本发明方法是在以1‑甲基‑2‑吡咯烷酮为溶剂,由苯硼酸、焦亚硫酸钾和硝基苯在六氟磷酸四乙腈铜/邻菲咯啉催化及异丙醇作还原剂条件下,于加热条件下反应,由苯硼酸、焦亚硫酸钾与铜催化剂作用产生亚磺酸盐中间体,再在铜作用下与硝基苯络合,络合物由异丙醇还原脱氧得羟胺中间体,进一步还原得到磺酰胺类化合物。本发明所述化合物制备方法优点在于由硝基苯出发,省去了通常制备方法中由芳香硝基化合物还原得芳胺的步骤,条件温和、简单高效、无需预先合成磺酰氯或亚磺酸钠类试剂、官能团兼容性强、底物的适用范围广。
Description
技术领域
本发明属有机化学技术领域,具体涉及一种磺酰胺类化合物的合成方法
背景技术
磺酰胺类化合物为一类含有磺酰基与氮原子相连接的有机化合物。其传统合成方法为使用相应的磺酰氯与胺进行反应,在碱的作用下脱去一分子氯化氢制得。
二氧化硫插入反应是一种得到广泛关注的新型有机合成策略,具体而言,即为在有机化学反应中“插入”一分子二氧化硫,从而合成含磺酰基化合物。其优势在于避免了传统含磺酰基化合物合成路线中强酸性磺酸或磺酰氯的使用与制备,而可通过一步直接完成磺酰基官能团的构建,具有简单高效、绿色环保的优点。近年来,针对现有磺酰胺类化合物的合成方法仍依赖于磺酰氯及磺酸盐类化合物的局限性,通过二氧化硫插入反应合成磺酰胺类化合物的反应方法得到了一定研究。[(a)B.Nguyen,E.J.Emmett,M.C.Willis,J.Am.Chem.Soc.2010,132,16372;(b)D.Zheng,Y.An,Z.Li,J.Wu,Angew.Chem.Int.Ed.2014,53,2451;(c)Y.Chen,P.R.D.Murray,A.T.Davies,M.C.Willis,J.Am.Chem.Soc.2018,140,8781;(d)M.Wang,Q.Fan,X.Jiang,Green Chem.2018,20,5469.]
芳香硝基化合物是一类极重要的化工原料,苯胺类化合物基本均由相应的芳香硝基化合物还原制得。因此,以芳香硝基化合物为原料,通过二氧化硫插入反应直接合成磺酰胺类化合物的方法具有极广阔的应用前景。
发明内容
本发明目的在于提供一种简便、高效的磺酰胺类化合物的合成方法。
本发明的优势在于:(1)使用芳香硝基化合物作为氮源,避免了传统步骤中先将硝基还原为氨基,再与磺酰类化合物反应的步骤;(2)使用二氧化硫插入策略,使用已非常成熟商业化的硼酸类化合物作为反应原料,无需预先合成磺酰氯或磺酸盐类化合物即可方便高效地合成各种磺酰胺类产物,具有广阔的药物化学与工业合成价值。
本发明方法是在酰胺类溶剂中,由有机硼酸、焦亚硫酸盐和硝基化合物在铜盐/配体催化及还原剂条件下加热反应,由有机硼酸、焦亚硫酸盐与铜催化剂作用产生亚磺酸盐中间体,再在铜作用下与硝基化合物络合,络合物由还原脱氧得羟胺中间体,进一步还原得到磺酰胺类化合物。
本发明提供的磺酰胺类化合物的合成方法,是利用有机硼酸、焦亚硫酸盐和芳香硝基化合物,添加还原剂,在有机溶剂中、铜/配体催化及加热条件下的偶联反应,高效构建磺酰胺类化合物。
具体而言,本发明方法是在有机溶剂(如1-甲基-2-吡咯烷酮)中,由苯硼酸、焦亚硫酸钾和硝基苯在六氟磷酸四乙腈铜/邻菲咯啉催化及异丙醇作还原剂条件下,于70摄氏度下反应,由苯硼酸、焦亚硫酸钾与铜催化剂作用产生亚磺酸盐中间体,再在铜作用下与硝基苯络合,络合物由异丙醇还原脱氧得羟胺中间体,进一步还原得到磺酰胺类化合物,其反应式为:
式中,(Het)Ar1为吸电子或供电子的苯基或杂环取代基,吸电子基团包括氟、氯、溴、三氟甲基、酰基和酯基取代基团,供电子基团包括烷基、烷氧基和取代氨基基团,杂环为缺电子或富电子杂环。
(Het)Ar2为吸电子或供电子的苯基或杂环取代基,吸电子基团包括氟、氯、溴和酰基取代基团,供电子基团包括烷基、烷氧基和取代氨基基团,杂环为缺电子或富电子杂环。
本发明方法的具体步骤如下:
(1)在室温下,向干燥的试管中加入0.2mmol的硝基化合物、0.6mmol焦亚硫酸钾、0.6mmol芳基硼酸、0.04mmol的六氟磷酸四乙腈铜(I)以及0.02mmol邻菲咯啉,用塞子塞好反应管后置于高纯氮气或者氩气中置换气,使得体系处于无水无氧条件后加入2.0mL的干燥1-甲基-2-吡咯烷酮和0.4mmol的异丙醇,置于70℃加热装置中搅拌48h;
(2)继TLC监测完全反应后,将反应液倒入80mL水中,用乙酸乙酯萃取(20 mL×3),有机相合并后用饱和食盐水洗涤两次,经无水硫酸钠干燥后减压浓缩,并采用石油醚和乙酸乙酯的混合液作为流动相进行柱层析分离,即可得到相应磺酰胺类化合物。
本发明的反应收率可达70%以上。
本发明的方法合成的该类化合物的结构经1H NMR、13C NMR、HRMS等方法表征并得以确认。
本发明中,所用的有机溶剂优选为1-甲基-2-吡咯烷酮(NMP),次备选项可为二甲基乙酰胺(DMAc),N,N-二甲基丙烯基脲(DMPU),N,N-二甲基咪唑啉酮(DMI)等。在以上若干溶剂中反应收率会有一定降低。
本发明中,所用的芳基硼酸中的芳基为吸电子或供电子的苯基或杂环取代基,吸电子基团包括氟、氯、溴、三氟甲基、酰基和酯基取代基团,供电子基团包括烷基、烷氧基和取代氨基基团,杂环为缺电子或富电子杂环。。
本发明中,所用的硝基化合物中的芳基为吸电子或供电子的苯基或杂环取代基,吸电子基团包括氟、氯、溴、酰基取代基团,供电子基团包括烷基、烷氧基、取代氨基基团,杂环为缺电子或富电子杂环。
本发明中,所用的铜催化剂为六氟磷酸四乙腈铜(I),次备选项可为四氟硼酸四乙腈铜(I),三氟甲烷磺酸铜,氯化亚铜等一价或二价的可溶性铜盐。更换铜催化剂反应收率会有一定降低。
本发明中,所用的配体为邻菲咯啉,次备选项可为取代邻菲咯啉、2,2’-联吡啶、取代2,2’-联吡啶、1,2-双(二苯基膦)乙烷及其他双齿氮、膦配体。更换配体反应收率会有一定降低。
本发明中,所用的还原剂优选为异丙醇,次备选项可为1,1,1,3,3,3-六氟异丙醇、亚硫酸钠、亚硫酸氢钠、2,6-二甲基-3,5-吡啶二羧酸二甲酯,2,6-二甲基-3,5-吡啶二羧酸二乙酯、1,4-环己二烯、对苯二酚等可给出氢或接受氧的化合物。更换还原剂反应收率会有一定降低。本发明中选用异丙醇为还原剂的主要原因为廉价、高效、不引入难挥发有机化合物、便于后处理及分离分析。
本发明中,以芳香硝基化合物为1.0当量计,焦亚硫酸钾的用量优选为3当量,较次备选用量为2.0-2.5当量;芳基硼酸的用量为3当量,较次备选用量为2.0-2.5当量;六氟磷酸四乙腈铜(I)的用量为0.2当量,较次备选用量为0.05-0.1当量,邻菲咯啉的用量为0.1当量,较次备选用量为0.05当量。以上替换会对反应收率造成一定降低。
本发明中,反应温度优选为70℃,备选温度为80℃,在上述范围内改变反应温度对反应收率无显著影响。
本发明方法是在酰胺类溶剂中,由有机硼酸、焦亚硫酸盐和硝基化合物在铜盐/配体催化及还原剂条件下加热反应,由有机硼酸、焦亚硫酸盐与铜催化剂作用产生亚磺酸盐中间体,再在铜作用下与硝基化合物络合,络合物由还原脱氧得羟胺中间体,进一步还原得到磺酰胺类化合物。
具体实施方式
下面通过具体实施例进一步描述本发明。
实施例1
在室温下,向干燥的试管中加入3当量的焦亚硫酸钾、3当量的2-萘硼酸、0.2当量的六氟磷酸四乙腈铜(I)以及0.1当量邻菲咯啉,用塞子塞好反应管后置于高纯氩气中置换气,使得体系处于无水无氧条件后加入干燥的1-甲基-2-吡咯烷酮、1当量的硝基苯和2当量的异丙醇,置于70℃加热装置中搅拌48h。继TLC监测完全反应后,将反应液用0.1M盐酸淬灭后倒入80mL水中,用乙酸乙酯萃取,有机相合并后用饱和食盐水洗涤两次,经无水硫酸钠干燥后减压浓缩,并采用4∶1石油醚和乙酸乙酯的混合液作为流动相进行柱层析分离,即可得到相应N-苯基-2-萘磺酰胺N-phenylnaphthalene-2-sulfonamide例1。
化合物例1的结构表征:1H NMR(400MHz,Acetone-d6)δ9.12(s,1H),8.42(s,1H),8.04(t,J=9.0Hz,2H),7.97(d,J=7.9Hz,1H),7.81(d,J=8.7Hz,1H),7.69-7.56(m,2H),7.28-7.15(m,4H),7.04-6.98(m,1H).13C NMR(101MHz,Acetone)δ137.81,136.98,134.79,132.04,129.23,129.14,129.05,128.79,128.34,127.84,127.54,124.46,122.36,120.77.
实施例2
在室温下,向干燥的试管中加入1当量的1-氯-4-硝基苯、3当量焦亚硫酸钾、3当量3-氯苯硼酸、0.2当量的六氟磷酸四乙腈铜(I)以及0.1当量邻菲咯啉,用塞子塞好反应管后置于高纯氩气中置换气,使得体系处于无水无氧条件后加入干燥的1-甲基-2-吡咯烷酮和2当量的异丙醇,置于70℃加热装置中搅拌48h。继TLC监测完全反应后,将反应液用0.1M盐酸淬灭后倒入80mL水中,用乙酸乙酯萃取,有机相合并后用饱和食盐水洗涤两次,经无水硫酸钠干燥后减压浓缩,并采用4∶1石油醚和乙酸乙酯的混合液作为流动相进行柱层析分离,即可得到相应N-(4-氯苯基)-4-氯苯磺酰胺3-Chloro-N-(4-chlorophenyl)benzenesulfonamide例2。化合物例2的结构表征:1H NMR(400MHz,CDCl3)δ7.79(s,1H),7.62(d,J=7.8Hz,1H),7.54(d,J=7.9Hz,1H),7.40(t,J=7.8Hz,1H),7.24(d,J=7.2Hz,2H),7.04(d,J=7.3Hz,2H),6.93(s,1H).13C NMR(101MHz,CDCl3)δ140.31,135.43,134.34,133.41,131.63,130.42,129.60,127.22,125.29,123.40.
实施例3
在室温下,向干燥的试管中加入1当量的4-硝基碘苯、3当量焦亚硫酸钾、3当量4-氯苯硼酸、0.2当量的六氟磷酸四乙腈铜(I)以及0.1当量邻菲咯啉,用塞子塞好反应管后置于高纯氩气中置换气,使得体系处于无水无氧条件后加入干燥的1-甲基-2-吡咯烷酮和2当量的异丙醇,置于70℃加热装置中搅拌48h。继TLC监测完全反应后,将反应液用0.1M盐酸淬灭后倒入80mL水中,用乙酸乙酯萃取,有机相合并后用饱和食盐水洗涤两次,经无水硫酸钠干燥后减压浓缩,并采用4∶1石油醚和乙酸乙酯的混合液作为流动相进行柱层析分离,即可得到相应N-(4-碘苯基)-4-氯苯磺酰胺4-Chloro-N-(4-iodophenyl)benzenesulfonamide例3。
化合物例3的结构表征:1H NMR(400MHz,Acetone-d6)δ9.13(broad,1H),7.80(d,J=8.7Hz,2H),7.63-7.57(m,4H),7.05(d,J=8.8Hz,2H).13C NMR(101MHz,Acetone-d6)δ138.67,138.34,136.89,132.19,129.32,128.84,122.85,117.37.
实施例4
在室温下,向干燥的试管中加入1当量的4-硝基苯甲醛、3当量焦亚硫酸钾、3当量4-氯苯硼酸、0.2当量的六氟磷酸四乙腈铜(I)以及0.1当量邻菲咯啉,用塞子塞好反应管后置于高纯氩气中置换气,使得体系处于无水无氧条件后加入干燥的1-甲基-2-吡咯烷酮和2当量的异丙醇,置于70℃加热装置中搅拌48h。继TLC监测完全反应后,将反应液用0.1M盐酸淬灭后倒入80mL水中,用乙酸乙酯萃取,有机相合并后用饱和食盐水洗涤两次,经无水硫酸钠干燥后减压浓缩,并采用2∶1石油醚和乙酸乙酯的混合液作为流动相进行柱层析分离,即可得到相应N-(4-甲酰基苯基)-4-氯苯磺酰胺4-Chloro-N-(4-formylphenyl)benzenesulfonamide例4。化合物例4的结构表征:1H NMR(400MHz,Acetone-d6)δ9.90(s,1H),9.68(s,1H),7.91(d,J=7.8Hz,2H),7.83(d,J=7.8Hz,2H),7.61(d,J=7.8Hz,2H),7.43(d,J=7.8Hz,2H).13C NMR(101MHz,Acetone-d6)δ206.26,191.58,139.42,136.81,133.70,131.94,130.49,129.91,128.56,120.05.
实施例5
在室温下,向干燥的试管中加入1当量的替硝唑、3当量焦亚硫酸钾、3当量4-氯苯硼酸、0.2当量的六氟磷酸四乙腈铜(I)以及0.1当量邻菲咯啉,用塞子塞好反应管后置于高纯氩气中置换气,使得体系处于无水无氧条件后加入干燥的1-甲基-2-吡咯烷酮和2当量的异丙醇,置于70℃加热装置中搅拌48h。继TLC监测完全反应后,将反应液用碳酸氢钠溶液淬灭后倒入80mL水中,用乙酸乙酯萃取,有机相合并后用饱和食盐水洗涤两次,经无水硫酸钠干燥后减压浓缩,并采用30∶1二氯甲烷和甲醇的混合液作为流动相进行柱层析分离,即可得到相应目标化合物4-chloro-N-(1-(2-(ethylsulfonyl)ethyl)-2-methyl-1H-imidazol-5-yl)benzenesulfonamide例5。
化合物例5的结构表征:1H NMR(400MHz,Acetone-d6)δ7.90(d,J=8.6Hz,2H),7.58(d,J=8.6Hz,2H),5.60(broad,1H),5.58(s,1H),4.34(t,J=6.9Hz,2H),3.59(t,J=6.9Hz,2H),3.05(q,J=7.5Hz,2H),2.26(s,3H),1.28(t,J=7.5Hz,3H).13C NMR(101MHz,Acetone-d6)δ144.35,143.75,141.07,138.74,129.95,129.25,50.11,48.66,36.94,13.38,6.55.
实施例6
在室温下,向干燥的试管中加入1当量的氟他胺、3当量焦亚硫酸钾、3当量4-氯苯硼酸、0.2当量的六氟磷酸四乙腈铜(I)以及0.1当量邻菲咯啉,用塞子塞好反应管后置于高纯氩气中置换气,使得体系处于无水无氧条件后加入干燥的1-甲基-2-吡咯烷酮和2当量的异丙醇,置于70℃加热装置中搅拌48h。继TLC监测完全反应后,将反应液用倒入80mL水中,用乙酸乙酯萃取,有机相合并后用饱和食盐水洗涤两次,经无水硫酸钠干燥后减压浓缩,并采用2∶1石油醚和乙酸乙酯的混合液作为流动相进行柱层析分离,即可得到相应目标化合物N-(4-((4-Chlorophenyl)sulfonamido)-3-(trifluoromethyl)phenyl)isobutyramide例6.
化合物例6的结构表征:1H NMR(400MHz,Acetone-d6)δ9.39(s,1H),8.57(s,1H),8.14(s,1H),7.84(d,J=8.7Hz,1H),7.79(d,J=7.6Hz,2H),7.62(d,J=7.7Hz,2H),7.39(d,J=8.7Hz,1H),2.63(dt,J=13.3,6.6Hz,1H),1.16(d,J=6.6Hz,6H).13C NMR(101MHz,Acetone-d6)δ176.53,140.52,139.54(d,JF=18.8Hz),130.16,130.09,129.79,129.04,126.67(q,JF=29.9Hz),125.55,123.76,122.83,117.94(q,JF=5.5Hz),36.70,19.72.19FNMR(376MHz,Acetone-d6)δ-60.24.
实施例7
在室温下,向干燥的试管中加入1当量的西尼地平、3当量焦亚硫酸钾、3当量4-氯苯硼酸、0.2当量的六氟磷酸四乙腈铜(I)以及0.1当量邻菲咯啉,用塞子塞好反应管后置于高纯氩气中置换气,使得体系处于无水无氧条件后加入干燥的1-甲基-2-吡咯烷酮和2当量的异丙醇,置于70℃加热装置中搅拌48h。继TLC监测完全反应后,将反应液用倒入80mL水中,用乙酸乙酯萃取,有机相合并后用饱和食盐水洗涤两次,经无水硫酸钠干燥后减压浓缩,并采用2∶1石油醚和乙酸乙酯的混合液作为流动相进行柱层析分离,即可得到相应目标化合物3-Cinnamyl 5-(2-methoxyethyl)4-(3-((4-chlorophenyl)sulfonamido)phenyl)-2,6-dimethyl-
1,4-dihydropyridine-3,5-dicarboxylate例7.
化合物例7的结构表征:1H NMR(400MHz,Acetone-d6)δ8.91(broad,1H),8.00(s,1H),7.71(d,J=7.4Hz,2H),7.47(d,J=7.5Hz,2H),7.38(d,J=7.3Hz,2H),7.34-7.29(m,3H),7.24(t,J=7.0Hz,1H),7.13-7.03(m,2H),6.90(d,J=7.5Hz,1H),6.51(d,J=16.0Hz,1H),6.36-6.26(m,1H),5.07(s,1H),4.70(qd,J=13.7,5.6Hz,2H),4.14(s,2H),3.52(s,2H),3.26(s,3H),2.38(s,3H),2.33(s,3H).13C NMR(101MHz,Acetone-d6)δ167.87,167.58,150.50,146.80,146.25,139.65,139.26,138.34,137.62,133.18,130.08,129.78,129.49,129.43,128.63,127.43,125.39,121.07,119.67,103.59,103.18,71.31,64.44,63.42,58.87,40.23,18.93.
本技术领域中的技术人员应当认识到,以上的实例仅是用来说明本发明,而非用作为对本发明的限定,只要在本发明的实质精神范围内,对以上所述实施例的变化,变型都将落在本发明的权利要求范围内。
Claims (10)
2.如权利要求1所述磺酰胺类化合物的合成方法,其特征在于,在有机溶剂中,由芳基硼酸、焦亚硫酸钾和芳香族硝基化合物在铜催化剂、配体以及还原剂作用下,于70-80摄氏度下反应,由芳基硼酸、焦亚硫酸钾与铜催化剂作用产生亚磺酸盐中间体,再在铜作用下与硝基化合物络合,络合物由还原剂还原脱氧得羟胺中间体,进一步还原得到磺酰胺类化合物。
3.根据权利要求2所述的合成方法,其特征在于,所述芳基硼酸中的芳基为吸电子或供电子的苯基或杂环取代基,吸电子基团包括氟、氯、溴、碘、三氟甲基、酰基和酯基取代基团,供电子基团为烷基、烷氧基和取代氨基基团,杂环为缺电子或富电子杂环。
4.根据权利要求2所述的合成方法,其特征在于,所述芳香族硝基化合物中的芳基为吸电子或供电子的苯基或杂环取代基,吸电子基团包括氟、氯、溴和酰基取代基团,供电子基团包括烷基、烷氧基和取代氨基基团,杂环为缺电子或富电子杂环。
5.根据权利要求2所述的合成方法,其特征在于,所述有机溶剂为1-甲基-2-吡咯烷酮、二甲基乙酰胺、N,N-二甲基丙烯基脲和N,N-二甲基咪唑啉酮中的任意一种。
6.根据权利要求2所述的合成方法,其特征在于,所述铜催化剂为六氟磷酸四乙腈铜(I)、四氟硼酸四乙腈铜(I)、三氟甲烷磺酸铜和氯化亚铜中的任意一种。
7.根据权利要求2所述的制备方法,其特征在于,所述配体为邻菲咯啉、取代邻菲咯啉、2,2’-联吡啶、取代2,2’-联吡啶、1,2-双(二苯基膦)乙烷及其他双齿氮配体和双膦配体。
8.根据权利要求2所述的合成方法,其特征在于,所述还原剂为异丙醇、1,1,1,3,3,3-六氟异丙醇、亚硫酸钠、亚硫酸氢钠、2,6-二甲基-3,5-吡啶二羧酸二甲酯、2,6-二甲基-3,5-吡啶二羧酸二乙酯、1,4-环己二烯和对苯二酚中的任意一种。
9.根据权利要求2所述的合成方法,其特征在于,以芳香簇硝基化合物为1.0当量计,焦亚硫酸钾的用量为2-3当量;芳基硼酸的用量为2-3当量;铜催化剂的用量为0.05-0.2当量,配体的用量为0.05-0.1当量。
10.根据权利要求2所述的制备方法,其特征在于,具体步骤如下:
(1)在室温下,向干燥的试管中加入0.2mmol的芳香族硝基化合物、0.6mmol焦亚硫酸钾、0.6mmol芳基硼酸、0.04mmol的六氟磷酸四乙腈铜(I)以及0.02mmol邻菲咯啉,用塞子塞好反应管后置于高纯氮气或者氩气中置换气,使得体系处于无水无氧条件后加入2.0mL的干燥1-甲基-2-吡咯烷酮和0.4mmol的异丙醇,置于70℃加热装置中搅拌48h;
(2)继TLC监测完全反应后,将反应液倒入80mL水中,用乙酸乙酯萃取,有机相合并后用饱和食盐水洗涤两次,经无水硫酸钠干燥后减压浓缩,并采用石油醚和乙酸乙酯的混合液作为流动相进行柱层析分离,即可得到相应磺酰胺类化合物;
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