CN115611781A - 一种由脂肪胺基磺酰氯制备烷基磺酰胺的新方法 - Google Patents
一种由脂肪胺基磺酰氯制备烷基磺酰胺的新方法 Download PDFInfo
- Publication number
- CN115611781A CN115611781A CN202110799183.8A CN202110799183A CN115611781A CN 115611781 A CN115611781 A CN 115611781A CN 202110799183 A CN202110799183 A CN 202110799183A CN 115611781 A CN115611781 A CN 115611781A
- Authority
- CN
- China
- Prior art keywords
- nmr
- cdcl
- thiophenol
- sulfonyl chloride
- derivative
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- -1 amine sulfonyl chloride Chemical class 0.000 title claims abstract description 111
- 238000000034 method Methods 0.000 title claims abstract description 14
- 125000004422 alkyl sulphonamide group Chemical group 0.000 title claims abstract description 12
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 claims abstract description 36
- 239000011941 photocatalyst Substances 0.000 claims abstract description 11
- 150000001336 alkenes Chemical class 0.000 claims abstract description 10
- 239000003638 chemical reducing agent Substances 0.000 claims abstract description 10
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims abstract description 10
- QAHVHSLSRLSVGS-UHFFFAOYSA-N sulfamoyl chloride Chemical compound NS(Cl)(=O)=O QAHVHSLSRLSVGS-UHFFFAOYSA-N 0.000 claims abstract description 9
- 229940124530 sulfonamide Drugs 0.000 claims abstract description 8
- 150000003456 sulfonamides Chemical class 0.000 claims abstract description 8
- 230000001699 photocatalysis Effects 0.000 claims abstract description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 5
- 238000005576 amination reaction Methods 0.000 claims abstract description 4
- 150000003254 radicals Chemical class 0.000 claims abstract description 4
- 230000009471 action Effects 0.000 claims abstract description 3
- 238000007342 radical addition reaction Methods 0.000 claims abstract description 3
- 239000002904 solvent Substances 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 43
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 18
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 12
- TXNLQUKVUJITMX-UHFFFAOYSA-N 4-tert-butyl-2-(4-tert-butylpyridin-2-yl)pyridine Chemical compound CC(C)(C)C1=CC=NC(C=2N=CC=C(C=2)C(C)(C)C)=C1 TXNLQUKVUJITMX-UHFFFAOYSA-N 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical group CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 6
- NIFAOMSJMGEFTQ-UHFFFAOYSA-N 4-methoxybenzenethiol Chemical compound COC1=CC=C(S)C=C1 NIFAOMSJMGEFTQ-UHFFFAOYSA-N 0.000 claims description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical group CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 4
- WLHCBQAPPJAULW-UHFFFAOYSA-N 4-methylbenzenethiol Chemical compound CC1=CC=C(S)C=C1 WLHCBQAPPJAULW-UHFFFAOYSA-N 0.000 claims description 3
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 3
- SEACYXSIPDVVMV-UHFFFAOYSA-L eosin Y Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C([O-])=C(Br)C=C21 SEACYXSIPDVVMV-UHFFFAOYSA-L 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical class CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 claims description 2
- KEJGAYKWRDILTF-JDDHQFAOSA-N (3ar,5s,6s,6ar)-5-[(4r)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyl-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxol-6-ol Chemical class O1C(C)(C)OC[C@@H]1[C@@H]1[C@H](O)[C@H]2OC(C)(C)O[C@H]2O1 KEJGAYKWRDILTF-JDDHQFAOSA-N 0.000 claims description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 2
- VQGHOUODWALEFC-UHFFFAOYSA-N 2-phenylpyridine Chemical compound C1=CC=CC=C1C1=CC=CC=N1 VQGHOUODWALEFC-UHFFFAOYSA-N 0.000 claims description 2
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 2
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- AXBVSRMHOPMXBA-UHFFFAOYSA-N 4-nitrothiophenol Chemical compound [O-][N+](=O)C1=CC=C(S)C=C1 AXBVSRMHOPMXBA-UHFFFAOYSA-N 0.000 claims description 2
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 2
- NEZONWMXZKDMKF-JTQLQIEISA-N Alkannin Chemical class C1=CC(O)=C2C(=O)C([C@@H](O)CC=C(C)C)=CC(=O)C2=C1O NEZONWMXZKDMKF-JTQLQIEISA-N 0.000 claims description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical group C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 2
- 150000002167 estrones Chemical class 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- 125000005322 morpholin-1-yl group Chemical group 0.000 claims description 2
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 2
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
- 239000003208 petroleum Substances 0.000 claims description 2
- 238000007146 photocatalysis Methods 0.000 claims description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 150000003568 thioethers Chemical class 0.000 claims description 2
- 239000012300 argon atmosphere Substances 0.000 claims 1
- 125000001624 naphthyl group Chemical group 0.000 claims 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 4
- 229930014626 natural product Natural products 0.000 abstract description 4
- 239000000758 substrate Substances 0.000 abstract description 4
- 238000007306 functionalization reaction Methods 0.000 abstract description 3
- IZDRSEBCBNFCJA-UHFFFAOYSA-N 6-sulfonylcyclohexa-2,4-dien-1-ol Chemical compound OC1C=CC=CC1=S(=O)=O IZDRSEBCBNFCJA-UHFFFAOYSA-N 0.000 abstract 1
- 125000001424 substituent group Chemical group 0.000 abstract 1
- 239000007787 solid Substances 0.000 description 35
- 239000007858 starting material Substances 0.000 description 27
- JLBJTVDPSNHSKJ-UHFFFAOYSA-N 4-Methylstyrene Chemical compound CC1=CC=C(C=C)C=C1 JLBJTVDPSNHSKJ-UHFFFAOYSA-N 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- NDVAMUMVOJRAJV-UHFFFAOYSA-N 10h-phenanthren-9-one Chemical compound C1=CC=C2C(=O)CC3=CC=CC=C3C2=C1 NDVAMUMVOJRAJV-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- QUCRCMAGYMXUKA-UHFFFAOYSA-N CC(C)(C)OC(N1C2=CC=C(CCS(N(C)C)(=O)=O)C=C2C=C1)=O Chemical compound CC(C)(C)OC(N1C2=CC=C(CCS(N(C)C)(=O)=O)C=C2C=C1)=O QUCRCMAGYMXUKA-UHFFFAOYSA-N 0.000 description 3
- WKSDBJDINSQBCC-UHFFFAOYSA-N CC(C)(C)OC(N1C2=CC=C(CCS(NC)(=O)=O)C=C2C=C1)=O Chemical compound CC(C)(C)OC(N1C2=CC=C(CCS(NC)(=O)=O)C=C2C=C1)=O WKSDBJDINSQBCC-UHFFFAOYSA-N 0.000 description 3
- VOCCOPCSVXHAEL-UHFFFAOYSA-N n,n-dimethyl-2-(4-nitrophenyl)ethanesulfonamide Chemical compound CN(C)S(=O)(=O)CCC1=CC=C([N+]([O-])=O)C=C1 VOCCOPCSVXHAEL-UHFFFAOYSA-N 0.000 description 3
- YPJAOELRXBOUCI-UHFFFAOYSA-N n,n-dimethyl-2-phenylpropane-2-sulfonamide Chemical compound CN(C)S(=O)(=O)C(C)(C)C1=CC=CC=C1 YPJAOELRXBOUCI-UHFFFAOYSA-N 0.000 description 3
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 3
- LLLQQESOZZJGQC-UHFFFAOYSA-N tert-butyl 5-ethenylindole-1-carboxylate Chemical compound C=CC1=CC=C2N(C(=O)OC(C)(C)C)C=CC2=C1 LLLQQESOZZJGQC-UHFFFAOYSA-N 0.000 description 3
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 2
- KXYAVSFOJVUIHT-UHFFFAOYSA-N 2-vinylnaphthalene Chemical group C1=CC=CC2=CC(C=C)=CC=C21 KXYAVSFOJVUIHT-UHFFFAOYSA-N 0.000 description 2
- FUGYGGDSWSUORM-UHFFFAOYSA-N 4-hydroxystyrene Chemical compound OC1=CC=C(C=C)C=C1 FUGYGGDSWSUORM-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- DQXKOHDUMJLXKH-PHEQNACWSA-N (e)-n-[2-[2-[[(e)-oct-2-enoyl]amino]ethyldisulfanyl]ethyl]oct-2-enamide Chemical compound CCCCC\C=C\C(=O)NCCSSCCNC(=O)\C=C\CCCCC DQXKOHDUMJLXKH-PHEQNACWSA-N 0.000 description 1
- KEIFWROAQVVDBN-UHFFFAOYSA-N 1,2-dihydronaphthalene Chemical compound C1=CC=C2C=CCCC2=C1 KEIFWROAQVVDBN-UHFFFAOYSA-N 0.000 description 1
- SSZOCHFYWWVSAI-UHFFFAOYSA-N 1-bromo-2-ethenylbenzene Chemical compound BrC1=CC=CC=C1C=C SSZOCHFYWWVSAI-UHFFFAOYSA-N 0.000 description 1
- KQJQPCJDKBKSLV-UHFFFAOYSA-N 1-bromo-3-ethenylbenzene Chemical compound BrC1=CC=CC(C=C)=C1 KQJQPCJDKBKSLV-UHFFFAOYSA-N 0.000 description 1
- WGGLDBIZIQMEGH-UHFFFAOYSA-N 1-bromo-4-ethenylbenzene Chemical compound BrC1=CC=C(C=C)C=C1 WGGLDBIZIQMEGH-UHFFFAOYSA-N 0.000 description 1
- KTZVZZJJVJQZHV-UHFFFAOYSA-N 1-chloro-4-ethenylbenzene Chemical compound ClC1=CC=C(C=C)C=C1 KTZVZZJJVJQZHV-UHFFFAOYSA-N 0.000 description 1
- LVJZCPNIJXVIAT-UHFFFAOYSA-N 1-ethenyl-2,3,4,5,6-pentafluorobenzene Chemical compound FC1=C(F)C(F)=C(C=C)C(F)=C1F LVJZCPNIJXVIAT-UHFFFAOYSA-N 0.000 description 1
- NVZWEEGUWXZOKI-UHFFFAOYSA-N 1-ethenyl-2-methylbenzene Chemical compound CC1=CC=CC=C1C=C NVZWEEGUWXZOKI-UHFFFAOYSA-N 0.000 description 1
- CEWDRCQPGANDRS-UHFFFAOYSA-N 1-ethenyl-4-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(C=C)C=C1 CEWDRCQPGANDRS-UHFFFAOYSA-N 0.000 description 1
- JWVTWJNGILGLAT-UHFFFAOYSA-N 1-ethenyl-4-fluorobenzene Chemical compound FC1=CC=C(C=C)C=C1 JWVTWJNGILGLAT-UHFFFAOYSA-N 0.000 description 1
- UAJRSHJHFRVGMG-UHFFFAOYSA-N 1-ethenyl-4-methoxybenzene Chemical compound COC1=CC=C(C=C)C=C1 UAJRSHJHFRVGMG-UHFFFAOYSA-N 0.000 description 1
- YFZHODLXYNDBSM-UHFFFAOYSA-N 1-ethenyl-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(C=C)C=C1 YFZHODLXYNDBSM-UHFFFAOYSA-N 0.000 description 1
- QEDJMOONZLUIMC-UHFFFAOYSA-N 1-tert-butyl-4-ethenylbenzene Chemical compound CC(C)(C)C1=CC=C(C=C)C=C1 QEDJMOONZLUIMC-UHFFFAOYSA-N 0.000 description 1
- DLMYXFNCIVZCRA-UHFFFAOYSA-N 2-(4-methylphenyl)benzenethiol Chemical compound C1=CC(C)=CC=C1C1=CC=CC=C1S DLMYXFNCIVZCRA-UHFFFAOYSA-N 0.000 description 1
- RIPGVSBLNYALJM-UHFFFAOYSA-N 2-prop-1-en-2-yl-1,3-benzothiazole Chemical group C1=CC=C2SC(C(=C)C)=NC2=C1 RIPGVSBLNYALJM-UHFFFAOYSA-N 0.000 description 1
- ORNUPNRNNSVZTC-UHFFFAOYSA-N 2-vinylthiophene Chemical group C=CC1=CC=CS1 ORNUPNRNNSVZTC-UHFFFAOYSA-N 0.000 description 1
- GMPDOIGGGXSAPL-UHFFFAOYSA-N Phenyl vinyl sulfide Natural products C=CSC1=CC=CC=C1 GMPDOIGGGXSAPL-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- XYLMUPLGERFSHI-UHFFFAOYSA-N alpha-Methylstyrene Chemical group CC(=C)C1=CC=CC=C1 XYLMUPLGERFSHI-UHFFFAOYSA-N 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- JFCHSQDLLFJHOA-UHFFFAOYSA-N n,n-dimethylsulfamoyl chloride Chemical compound CN(C)S(Cl)(=O)=O JFCHSQDLLFJHOA-UHFFFAOYSA-N 0.000 description 1
- 150000002790 naphthalenes Chemical group 0.000 description 1
- 238000005935 nucleophilic addition reaction Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000006103 sulfonylation Effects 0.000 description 1
- 238000005694 sulfonylation reaction Methods 0.000 description 1
- 238000005987 sulfurization reaction Methods 0.000 description 1
- ZWQXDRJLUKYHII-UHFFFAOYSA-N tert-butyl 3-ethenylindole-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC(C)(C)C)C=C(C=C)C2=C1 ZWQXDRJLUKYHII-UHFFFAOYSA-N 0.000 description 1
- PQEXLIRUMIRSAL-UHFFFAOYSA-N tert-butyl 4-(2-ethoxy-2-oxoethyl)piperidine-1-carboxylate Chemical compound CCOC(=O)CC1CCN(C(=O)OC(C)(C)C)CC1 PQEXLIRUMIRSAL-UHFFFAOYSA-N 0.000 description 1
- TTYAAYBJWCDCLU-UHFFFAOYSA-N tert-butyl n-(4-ethenylphenyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=C(C=C)C=C1 TTYAAYBJWCDCLU-UHFFFAOYSA-N 0.000 description 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000004073 vulcanization Methods 0.000 description 1
Classifications
-
- 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
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B45/00—Formation or introduction of functional groups containing sulfur
-
- 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
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/26—Radicals substituted by sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/64—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/192—Radicals derived from carboxylic acids from aromatic carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/18—Radicals substituted by singly bound hetero atoms other than halogen by sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
- C07J1/0051—Estrane derivatives
- C07J1/0059—Estrane derivatives substituted in position 17 by a keto group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
Abstract
本发明提供一种由脂肪胺基磺酰氯在光催化条件下制备烷基磺酰胺的方法,如方程式1所示:取代烯烃A在一定溶剂中,氩气氛围,光催化剂、还原剂和硫酚共同作用,蓝光源照射下与脂肪胺基磺酰氯B发生自由基加成和硫酚协调氢原子转移的氢化磺酰胺化反应制得磺酰胺I。该方法条件温和,收率高,底物使用范围广,可用于复杂天然产物或药物分子的后期官能团化。R1‑R5所指代的取代基详见说明书。
Description
技术领域
本发明属于精细化学品技术领域,具体涉及光促进的由脂肪胺基磺酰氯制备烷基磺酰胺的方法,该方法可用于烷基磺酰胺类化合物的高效制备。
背景技术
在医药、农药和材料等领域,磺酰胺一直是一类重要的官能团,且广泛存在于多种天然产物和功能材料中(Science 2000,287,1960-1964;Chem.Rev.2019,119,8701-8780;Nat.Prod.Rep.2020,37,246-275;Top Curr.Chem.2017,375,82)。磺胺类药物具有良好的物理化学性能、化学和代谢稳定性、良好的药效和疗效(J.Med.Chem.2015,58,7381-7399;J.Med.Chem.2019,62,467-479)。迄今为止报道的大多数磺酰胺合成往往都需要硫化、氧化为磺酰氯,再与胺基亲核加成。由于反应步骤长、硫化条件苛刻和磺酰氯的高反应活性导致反应较差的选择性,限制了其在合成中的应用(J.Org.Chem.2009,74,9287-9291;Synlett.2011,16,2315-2320)。2020年,Gouverneur课题组报道一种可见光诱导Eosin Y催化的缺电子烯烃的氢化磺酰胺化反应(J.Am.Chem.Soc.2020,142,720-725)。近些年来,由于制药行业对富含C(sp3)的分子的需求不断增加,烷基磺酰胺类药物的合成方法仍面临着诸多的挑战(J.Med.Chem.2009,52,4111-4114;Chem.Rev.2010,110,4489-4497)。同时,以脂肪胺基磺酰氯为自由基源,不需羰基预活化烯烃的氢化磺酰胺化反应制备烷基磺酰胺的方法未见报道。
发明内容
本发明的目的是提供一种由脂肪胺基磺酰氯在光催化条件下制备烷基磺酰胺的方法。该方法条件温和,收率高,底物使用范围广,可用于复杂天然产物或药物分子的后期官能团化。
本发明的一种由脂肪胺基磺酰氯在光催化条件下制备烷基磺酰胺的方法如方程式1所示:取代烯烃A在一定溶剂中,氩气氛围,光催化剂、还原剂和硫酚共同作用,蓝光源照射下与脂肪胺基磺酰氯B发生自由基加成和硫酚协调氢原子转移的氢化磺酰胺化反应制得磺酰胺I。
方程式1
式中:R1为:苯基、4-甲基苯基、4-叔丁基苯基、4-甲氧基苯基、4-乙酰氧基苯基、4-甲酸酯基苯基、4-三氟甲基苯基、4-硝基苯基、4-氟苯基、4-氯苯基、4-溴苯基,4-羟基苯基、4-(N-Boc-胺基)苯基、2-甲基苯基、2-溴苯基、3-溴苯基、2,3,4,5,6-五氟苯基、取代萘环、喹啉环、噻吩环、苯并噻唑环、吲哚环、硫醚、酚噻唑酸衍生物、薄荷醇衍生物、双丙酮-D-葡萄糖衍生物、雌酚酮衍生物、H-Phe-Leu-OBzl衍生物或紫草素衍生物;R2为:甲基或苯基;R3为:甲基;R4和R5分别独立的为:氢、甲基、1-吗啉基、1-哌啶基或1-吡咯基。
本反应中烯烃(A)、光催化剂、硫酚、脂肪胺基磺酰氯(B)、还原剂的摩尔比是1∶0.002-0.2∶0.1-1∶1-5∶1-5。
反应温度范围为-30-80℃,最佳的反应温度为20-50℃。
本反应的反应时间为0.5-48小时,最佳反应时间为1-36小时。
在本发明中所使用的还原剂为N,N-二异丙基乙胺或汉斯酯。最佳还原剂为汉斯酯。
在本发明中所使用的硫酚为4-甲氧基苯硫酚、苯硫酚、4-甲氧基苯硫酚或4-硝基苯硫酚。最佳硫酚为4-甲基苯硫酚。
在本发明中所使用的有机溶剂选自乙醇、甲醇、环己烷、正己烷、正戊烷、正庚烷、石油醚、乙醚、四氢呋喃、二氯甲烷、三氯甲烷、四氯化碳、1,2-二氯乙烷和乙腈中的至少一种。最佳的有机溶剂为乙腈。
本反应在不加光催化剂或不加碱或不加还原剂或不光照的条件下,均不能发生。
本发明的光催化剂为[Ir{dF(CF3)ppy}2(dtbbpy)]PF6,[Ir(dtbbpy)(ppy)2]PF6,Eosin Y,Ru(bpy)3(PF6)2,Ir(ppy)3或Mes-Acr+。
烷基磺酰胺I的优选化合物为结构式1所示的化合物I-1~I-41:
结构式2
与现有技术相比,本发明具有突出的实质性特点和显著进步如下:该方法底物烯烃不需羰基的预活化,反应条件温和,收率高,底物使用范围广,可用于复杂天然产物或药物分子的后期官能团化。
具体实施方式
实施例1 磺酰胺I-1~I-35的合成
将1.0当量的烯烃A与1.0-5.0当量的二甲胺基磺酰氯、0.2-2.0mmol%的光催化剂[Ir(dF(CF3)ppy)2(dtbbpy)]PF6、1.0-5.0当量的汉斯酯、0.2-1.0当量4-甲基苯硫酚、2-5mL乙腈加入10mL Schlenk管,通过双排管,氩气抽放气3-5次,在15W的465~475nm蓝光照射下反应3~12小时,加入饱和NaCl溶液和二氯甲烷萃取,有机层干燥,真空减压脱溶,柱层析得到脂肪胺磺酰基环化产物纯品。
2-(4-甲基苯基)-N,N-二甲基胺基磺酰乙烷(I-1)
原料4-甲基苯乙烯(35.5mg,0.3mmol)得到化合物I-1(63.6mg,0.28mmol,94%),产物为白色固体,熔点96-98℃。1H NMR(400MHz,CDCl3)δ7.17-7.07(m,4H,Ar-H),3.18-3.12(m,2H,CH2),3.11-3.05(m,2H,CH2),2.87(s,6H,N-CH3),2.33(s,3H,Ar-CH3).13C NMR(100MHz,CDCl3)δ136.6,135.1,129.5,128.2,49.8,37.5,28.9,21.0.HRMS(ESI):Cacldfor C11H18NO2S[M+H]+228.1054,found 228.1057.
2-苯基-N,N-二甲基胺基磺酰乙烷(I-2)
原料苯乙烯(31.1mg,0.3mmol)得到化合物I-2(61.4mg,0.29mmol,96%),产物为白色固体,熔点60-62℃。1H NMR(400MHz,CDCl3)δ7.35-7.30(m,2H,Ar-H),7.26-7.21(m,3H,Ar-H),3.20-3.15(m,2H,CH2),3.14-3.09(m,2H,CH2),2.87(s,6H,N-CH3).13C NMR(100MHz,CDCl3)δ138.1,128.9,128.4,126.9,49.6,37.4,29.3.HRMS(ESI):Cacld for C10H16NO2S[M+H]+214.0896,found 214.0891.
2-(4-叔丁基苯基)-N,N-二甲基胺基磺酰乙烷(I-3)
原料4-叔丁基苯乙烯(48.1mg,0.3mmol)得到化合物I-3(71.9mg,0.27mmol,89%),产物为白色固体,熔点124-125℃。1H NMR(400MHz,CDCl3)δ7.38(d,J=8.1Hz,2H,Ar-H),7.19(d,J=8.1Hz,2H,Ar-H),3.24-3.15(m,2H,CH2),3.15-3.08(m,2H,CH2),2.90(s,6H,N-CH3),1.34(s,9H,CH3).13C NMR(100MHz,CDCl3)δ149.9,135.1,128.1,125.8,49.6,37.5,34.5,31.3,28.7.HRMS(ESI):Cacld for C14H24NO2S[M+H]+270.1522,found 270.1523.
2-(4-甲氧基苯基)-N,N-二甲基胺基磺酰乙烷(I-4)
原料4-甲氧基苯乙烯(40.3mg,0.3mmol)得到化合物I-4(74.0mg,0.29mmol,96%),产物为白色固体,熔点124-125℃。1H NMR(400MHz,CDCl3)δ7.14(d,J=8.6Hz,2H,Ar-H),6.86(d,J=8.6Hz,2H,Ar-H),3.78(d,J=8.7Hz,3H,O-CH3),3.18-3.10(m,2H,CH2),3.10-3.01(m,2H,CH2),2.87(s,6H,N-CH3).13C NMR(100MHz,CDCl3)δ130.1,130.0,129.4,114.3,55.3,49.9,37.5,28.5.HRMS(ESI):Cacld for C11H18NO3S[M+H]+244.1002,found244.1007.
乙酸-2-(N,N-二甲基胺基磺酰乙烷基)苯脂(I-5)
原料乙酸-2-乙烯基苯脂(48.7mg,0.3mmol)得到化合物I-5(51.1mg,0.25mmol,83%),产物为白色固体,熔点91-92℃。1H NMR(400MHz,CDCl3)δ7.23(d,J=8.3Hz,2H,Ar-H),7.04(d,J=8.3Hz,2H,Ar-H),3.20-3.06(m,4H,CH2),2.87(s,6H,N-CH3),2.29(s,3H,CO-CH3).13C NMR(100MHz,CDCl3)δ169.5,149.6,135.7,129.4,122.0,49.5,37.4,28.7,21.1.HRMS(ESI):Cacld for C12H18NO4S[M+H]+272.0951,found 272.0958.
2-(4-甲酸甲脂苯基)-N,N-二甲基胺基磺酰乙烷(I-6)
4-甲酸甲酯苯乙烯(48.7mg,0.3mmol)得到化合物I-6(60.2mg,0.22mmol,74%),产物为白色固体,熔点112-113℃。1H NMR(400MHz,CDCl3)δ8.00(d,J=8.3Hz,2H,Ar-H),7.30(d,J=8.2Hz,2H,Ar-H),3.91(s,3H,O-CH3),3.18(m,4H,CH2),2.88(s,6H,N-CH3).13CNMR(100MHz,CDCl3)δ166.8,143.4,130.2,128.5,52.2,49.1,37.4,29.3.HRMS(ESI):Cacldfor C12H18NO4S[M+H]+272.0951,found 272.0956.
2-(4-三氟甲基苯基)-N,N-二甲基胺基磺酰乙烷(I-7)
原料4-三氟甲基苯乙烯(51.7mg,0.3mmol)得到化合物I-7(67.6mg,0.24mmol,80%),产物为白色固体,熔点86-87℃。1H NMR(400MHz,CDCl3)δ7.58(d,J=8.1Hz,2H,Ar-H),7.35(d,J=8.0Hz,2H,Ar-H),3.20-3.16(m,4H,CH2),2.88(s,6H,N-CH3).13C NMR(100MHz,CDCl3)δ142.3,128.8,128.0,125.8-125.7(m,1C),49.1,37.4,29.2.HRMS(ESI):Cacld for C11H15F3NO2S[M+H]+282.0770,found 282.0773.
2-(4-硝基苯基)-N,N-二甲基胺基磺酰乙烷(I-8)
原料4-硝基苯乙烯(44.7mg,0.3mmol)得到化合物I-8(62.0mg,0.24mmol,80%),产物为棕色固体,熔点140-142℃。1H NMR(400MHz,CDCl3)δ8.20(d,J=8.6Hz,2H,Ar-H),7.41(d,J=8.6Hz,2H,Ar-H),3.32-3.22(m,2H,CH2),3.22-3.14(m,2H,CH2),2.90(s,6H,N-CH3).13C NMR(100MHz,CDCl3)δ145.7,129.4,124.1,48.8,37.5,29.2.HRMS(ESI):Cacldfor C10H15N2O4S[M+H]+259.0747,found 259.0743.
2-(4-氟苯基)-N,N-二甲基胺基磺酰乙烷(I-9)
原料4-氟苯乙烯(36.6mg,0.3mmol)得到化合物I-9(64.7mg,0.28mmol,93%),产物为黄色固体,熔点88-89℃。1H NMR(400MHz,CDCl3)δ7.22-7.15(m,2H,Ar-H),7.05-6.97(m,2H,Ar-H),3.18-3.06(m,4H,CH2),2.88(s,6H,N-CH3).13C NMR(100MHz,CDCl3)δ161.8(d,J=274.1Hz,1C),133.9(d,J=8.1Hz,1C),129.9,115.7(d,J=21.4Hz,1C),49.6,37.5,28.6.HRMS(ESI):Cacld for C10H15FNO2S[M+H]+232.0802,found 232.0809.
2-(4-氯苯基)-N,N-二甲基胺基磺酰乙烷(I-10)
原料4-氯苯乙烯(41.7mg,0.3mmol)得到化合物I-10(66.0mg,0.27mmol,89%),产物为白色固体,熔点130-131℃。1H NMR(400MHz,CDCl3)δ7.31-7.27(dd,J=3.1,1.2Hz,2H,Ar-H),7.18-7.13(dd,J=2.7,1.1Hz,2H,Ar-H),3.15-3.06(m,4H,CH2),2.88(s,6H,N-CH3).13C NMR(100MHz,CDCl3)δ136.6,132.8,129.8,129.0,49.4,37.5,28.7.HRMS(ESI):Cacldfor C10H15ClNO2S[M+H]+248.0507,found 248.0501.
2-(4-溴苯基)-N,N-二甲基胺基磺酰乙烷(I-11)
原料4-溴苯乙烯(54.9mg,0.3mmol)得到化合物I-11(69.7mg,0.24mmol,71%),产物为黄色固体,熔点132-134℃。1H NMR(400MHz,CDCl3)δ7.47(d,J=83Hz,2H,Ar-H),7.12(d,J=8.2Hz,2H,Ar-H),3.18-3.13(m,2H,CH2),3.13-3.06(m,2H,CH2),2.90(s,6H,N-CH3).13C NMR(100MHz,CDCl3)δ137.1,131.9,130.1,120.8,49.4,37.4,28.8.HRMS(ESI):Cacldfor C10H15BrNO2S[M+H]+292.0001,found 292.0004.
2-(4-羟基苯基)-N,N-二甲基胺基磺酰乙烷(I-12)
原料4-羟基苯乙烯(36.1mg,0.3mmol)得到化合物I-12(32.7mg,0.14mmol,48%),产物为棕色固体,熔点89-90℃。1H NMR(400MHz,CDCl3)δ7.07(d,J=8.2Hz,2H,Ar-H),6.80(d,J=8.4Hz,2H,Ar-H),5.41(s,1H,OH),3.17-3.10(m,2H,CH2),3.07-3.02(m,2H,CH2),2.87(s,6H,N-CH3).13C NMR(100MHz,CDCl3)δ154.7,129.9,129.6,115.7,49.9,37.5,28.4.HRMS(ESI):Cacld for C10H16NO3S[M+H]+230.0845,foumd 230.0844.
2-(4-(N-Boc-胺基)苯基)-N,,N-二甲基胺基磺酰乙烷(I-13)
原料4-(N-Boc-胺基)苯乙烯(66.1mg,0.3mmol)得到化合物I-13(76.6mg,0.23mmol,78%),产物为黄色油状物。1H NMR(400MHz,CDCl3)δ7.26-7.19(m,4H,Ar-H),3.19-3.10(m,4H,CH2),2.85(s,6H,N-CH3),1.45(s,9H,CH3).13C NMR(100MHz,CDCl3)δ154.7,151.9,137.7,128.8,128.4,83.5,49.5,37.4,29.0,28.0.HRMS(ESI):Cacld forC15H25N2O4S[M+H]+329.1530,found 329.1533.
2-(2-甲基苯基)-N,N-二甲基胺基磺酰乙烷(I-14)
原料2-甲基苯乙烯(35.5mg,0.3mmol)得到化合物I-14(64.8mg,0.29mmol,98%),产物为白色固体,熔点68-69℃。1H NMR(400MHz,CDCl3)δ7.17-7.13(m,J,4H),3.14-3.09(m,4H,CH2),2.89(s,6H,N-CH3),2.35(s,3H,Ar-CH3).13C NMR(100MHz,CDCl3)δ136.4,136.0,130.7,128.8,127.2,126.5,48.3,37.5,26.7,19.2.HRMS(ESI):Cacld for C11H18NO2S[M+H]+228.1053,found 228.1057.
2-(2-溴苯基)-N,N-二甲基胺基磺酰乙烷(I-15)
原料2-溴苯乙烯(54.9mg,0.3mmol)得到化合物I-15(62.3mg,0.21mmol,71%),产物为白色固体,熔点70-71℃。1H NMR(400MHz,CDCl3)δ7.55(d,J=7.8Hz,1H,Ar-H),7.30-7.26(m,2H,Ar-H),7.16-7.10(m,1H,Ar-H),3.26-3.19(m,4H,CH2),2.92(s,6H,N-CH3).13CNMR(100MHz,CDCl3)δ137.5,133.1,130.8,128.9,128.0,124.2,48.1,37.5,30.3.HRMS(ESI):Cacld for C10H15BrNO2S[M+H]+292.0001,found 292.0005.
2-(3-溴苯基)-N,N-二甲基胺基磺酰乙烷(I-16)
原料3-溴苯乙烯(54.9mg,0.3mmol)得到化合物I-16(65.4mg,0.22mmol,75%),产物为白色固体,熔点82-84℃。1H NMR(400MHz,CDCl3)δ7.41-7.35(m,2H,Ar-H),7.22-7.11(m,2H,Ar-H),3.17-3.13(m,2H,CH2),3.12-3.07(m,2H,CH2),2.88(s,6H,N-CH3).13C NMR(100MHz,CDCl3)δ140.4,131.4,130.4,130.1,127.1,122.8,49.3,37.5,29.0.HRMS(ESI):Cacld for C10H15BrNO2S[M+H]+292.0001,found 292.0008.
2-苯基-N,N-二甲基胺基磺酰丙烷(I-17)
原料2-苯基丙烯(35.5mg,0.3mmol)得到化合物I-17(46.1mg,0.20mmol,68%),产物为黄色油状物。1H NMR(400MHz,CDCl3)δ7.36-7.30(m,2H,Ar-H),7.26-7.2(m,3H,Ar-H),3.40(dd,J=13.6,7.0Hz,1H,SO2-CH2),3.21(dd,J=13.9,5.4Hz,1H,SO2-CH2),3.13-3.04(m,1H,Ar-CH),2.72(s,6H,N-CH3),1.47(d,J=7.0Hz,3H,CH3).13C NMR(100MHz,CDCl3)δ144.7,128.9,127.0,126.8,55.1,37.2,35.5,22.0.HRMS(ESI):Cacld for C11H18NO2S[M+H]+228.1053,found 228.1047.
2,2-二苯基-N,N-二甲基胺基磺酰乙烷(I-18)
原料1,1-二苯乙烯(54.1mg,0.3mmol)得到化合物I-18(57.8mg,0.20mmol,67%),产物为白色固体,熔点96-97℃。1H NMR(400MHz,CDCl3)δ7.35-7.26(m,10H,Ar-H),4.60(t,J=7.0Hz,1H,Ar-CH),3.72(d,J=7.0Hz,2H,SO2-CH2),2.55(s,6H,N-CH3).13C NMR(100MHz,CDCl3)δ142.1,128.9,127.6,127.1,54.8,46.5,36.7.HRMS(ESI):Cacld for C16H20NO2S[M+H]+290.1209,found 290.1207.
2-苯基-2-(N,,N-二甲基胺基磺酰基)丙烷(I-19)
原料Z/E-1-苯基丙烯(35.5mg,0.3mmol)得到化合物I-19(20.0mg,0.09mmol,29%),产物为黄色油状物。1H NMR(400MHz,CDCl3)δ7.34-7.30(m,2H,Ar-H),7.27-7.25(m,1H,Ar-H),7.18(d,J=7.0Hz,2H,Ar-H),3.43-3.35(dd,J=13.1,10.1Hz,1H,Ar-CH2),3.36-3.25(m,1H,SO2-CH),2.95(s,6H,N-CH3),2.66(dd,J=13.3,11.1Hz,1H,Ar-CH2),1.22(d,J=6.8Hz,3H,CH3).13C NMR(100MHz,CDCl3)δ137.5,129.2,128.7,126.9,58.7,37.9,36.7,13.5.HRMS(ESI):Cacld for C11H18NO2S[M+H]+228.1053,found 228.1057.
2-(2,3,4,5,6-五氟苯基)-N,N-二甲基胺基磺酰乙烷(I-20)
原料2,3,4,5,6-五氟苯乙烯(58.2mg,0.3mmol)得到化合物I-20(59.7mg,0.20mmol,66%),产物为棕色固体,熔点66-68℃。1H NMR(400MHz,CDCl3)δ3.24-3.18(m,2H,CH2),3.19-3.11(m,2H,CH2),2.91(s,6H,N-CH3).13C NMR(100MHz,CDCl3)δ46.5,37.4,37.2.HRMS(ESI):Cacld for C10H11F5NO2S[M+H]+304.0425,found 304.0427.
2-(2-萘基)-N,N-二甲基胺基磺酰乙烷(I-21)
原料2-萘乙烯(42.3mg,0.3mmol)得到化合物I-21(74.3mg,0.28mmol,94%),产物为白色固体,熔点89-91℃。1H NMR(400MHz,CDCl3)δ7.83-7.77(m,3H,Ar-H),7.67(s,1H,Ar-H),7.49-7.43(m,2H,Ar-H),7.33(dd,J=8.4,1.7Hz,1H,Ar-H),3.30-3.23(m,4H,CH2),2.88(s,6H,N-CH3).13C NMR(100MHz,CDCl3)δ135.6,133.6,132.4,128.6,127.7,127.5,126.8,126.6,126.4,125.9,49.6,37.5,29.5.HRMS(ESI):Cacld for C14H18NO2S[M+H]+264.1053,found 264.1059.
2-(2-喹啉)-N,N-二甲基胺基磺酰乙烷(I-22)
原料2-萘乙烯(42.3mg,0.3mmol)得到化合物I-22(40.1mg,0.15mmol,51%),产物为黄色固体,熔点104-106℃。1H NMR(400MHz,CDCl3)δ8.11(d,J=8.4Hz,1H,Ar-H),8.04(d,J=8.5Hz,1H,Ar-H),7.81(d,J=8.1Hz,1H,Ar-H),7.73-7.69(m,1H,Ar-H),7.56-7.50(m,1H,Ar-H),7.33(d,J=8.4Hz,1H,Ar-H),3.67-3.57(m,2H,CH2),3.51-3.47(m,2H,CH2),2.87(s,6H,N-CH3).13C NMR(100MHz,CDCl3)δ158.0,147.7,136.9,129.8,128.7,127.7,127.0,126.3,121.5,46.8,37.4,31.8.HRMS(ESI):Cacld for C13H17N2O2S[M+H]+265.1005,found265.1001.
2-(2-噻吩)-N,N-二甲基胺基磺酰乙烷(I-23)
原料2-噻吩乙烯(42.3mg,0.3mmol)得到化合物I-23(33.1mg,0.19mmol,63%),产物为棕色固体,熔点76-77℃。1H NMR(400MHz,CDCl3)δ7.18(dd,J=5.1,1.1Hz,1H,Ar-H),6.94(dd,J=5.1,3.5Hz,1H,Ar-H),6.89-6.86(m,1H,Ar-H),3.37-3.33(m,2H,CH2),3.26-3.20(m,2H,CH2),2.88(s,6H,N-CH3).13C NMR(100MHz,CDCl3)δ140.4,127.2,125.5,124.3,49.9,37.4,23.8.HRMS(ESI):Cacld for C8H14NO2S2[M+H]+220.0460,found 220.0461.
2-(2-苯并噻唑)-N,N-二甲基胺基磺酰丙烷(I-24)
原料2-苯并噻唑丙烯(52.6mg,0.3mmol)得到化合物I-24(36.6mg,0.14mmol,45%),产物为棕色油状物。1H NMR(400MHz,CDCl3)δ7.98(d,J=8.0Hz,1H,Ar-H),7.87(d,J=8.1Hz,1H,Ar-H),7.48(t,J=7.7Hz,1H,Ar-H),7.39(t,J=7.6Hz,1H,Ar-H),3.95-3.81(m,2H,CH2),3.27-3.22(m,1H),2.81(s,6H,N-CH3),1.68(d,J=6.8Hz,3H,CH3).13C NMR(100MHz,CDCl3)δ173.8,152.9,134.8,126.2,125.2,122.8,121.8,52.9,37.3,34.6,21.7.HRMS(ESI):Cacld for C12H17N2O2S2[M+H]+285.0726,found 285.0728.
3-(2-(N,N-二甲基胺基磺酰基)乙基)-N-Boc吲哚(I-25)
原料3-乙烯基-N-Boc吲哚(73.3mg,0.3mmol)得到化合物I-25(78.2mg,0.22mmol,74%),产物为黄色固体,熔点91-92℃。1H NMR(400MHz,CDCl3)δ8.14(d,J=7.3Hz,1H,Ar-H),7.53(d,J=7.6Hz,1H,Ar-H),7.44(s,1H,Ar-H),7.37-7.32(m,1H,Ar-H),7.29-7.25(m,1H,Ar-H),3.29-3.19(m,4H,CH2),2.91(s,6H,N-CH3),1.67(s,9H,CH3).13C NMR(100MHz,CDCl3)δ124.8,123.0,122.73,118.5,117.1,115.5,47.9,37.5,28.2,19.1.HRMS(ESI):Cacld for C17H25N2O4S[M+H]+353.1530,found 353.1534.
5-(2-(N,N-二甲基胺基磺酰基)乙基)-N-Boc吲哚(I-26)
原料5-乙烯基-N-Boc吲哚(73.3mg,0.3mmol)得到化合物I-26(92.0mg,0.26mmol,87%),产物为棕色固体,熔点73-74℃。1H NMR(400MHz,CDCl3)δ8.08(d,J=8.2Hz,1H,Ar-H),7.59(d,J=3.6Hz,1H,Ar-H),7.40(d,J=1.4Hz,1H,Ar-H),7.16(dd,J=8.5,1.7Hz,1H,Ar-H),6.52(d,J=3.7Hz,1H,Ar-H),3.21(m,4H,CH2),2.88(s,6H,N-CH3),1.67(s,9H,CH3).13C NMR(100MHz,CDCl3)δ149.7,132.4,131.0,126.5,124.5,120.5,115.5,107.0,83.8,50.2,37.5,29.3,28.2.HRMS(ESI):Cacld for C17H25N2O4S[M+H]+353.1530,found353.1533.
2,3-二氢-2-(N,N-二甲基胺基磺酰基)-1H-茚(I-27)
原料茚(34.9mg,0.3mmol)得到化合物I-27(51.4mg,0.20mmol,68%),产物为棕色固体,熔点129-130℃。1H NMR(400MHz,CDCl3)δ7.26-7.15(m,4H,Ar-H),4.10-3.96(m,1H,SO2-CH),3.45(dd,J=16.2,7.7Hz,2H,Ar-CH2),3.28(dd,J=16.2,8.7Hz,2H,Ar-CH2),2.87(s,6H,N-CH3).13C NMR(100MHz,CDCl3)δ139.8,127.2,124.4,60.0,37.8,34.6.HRMS(ESI):Cacld for C11H16NO2S[M+H]+226.0896,found 226.0899.
1,2,3,4-四氢-2-(N,N-二甲基胺基磺酰基)萘(I-28)
原料1,2-二氢萘(39.1mg,0.3mmol)得到化合物I-28(52.4mg,0.20mmol,65%),产物为棕色固体,熔点106-107℃。1H NMR(400MHz,CDCl3)δ7.16-7.10(m,4H),3.44-3.34(m,1H,SO2-CH),3.12(d,J=8.5Hz,2H,Ar-CH2),2.97(d,J=4.9Hz,6H,N-CH3),2.98-2.93(m,1H,Ar-CH2),2.92-2.84(m,1H,Ar-CH2),2.43-2.34(m,1H,CH2),2.02-1.98(m,1H,CH2).13CNMR(100MHz,CDCl3)δ135.0,133.3,129.1,128.8,126.5,126.3,57.6,38.0,29.7,28.4,23.7.HRMS(ESI):Cacld for C12H18NO2S[M+H]+240.1053,found 240.1052.
2-苯硫基-1-(N,N-二甲基胺基磺酰基)乙烷(I-29)
原料苯基乙烯基硫醚(40.9mg,0.3mmol)得到化合物I-29(65.3mg,0.27mmol,89%),产物为白色固体,熔点70-71℃。1H NMR(400MHz,CDCl3)δ7.39-7.30(m,4H,Ar-H),7.27-7.23(m,1H,Ar-H),3.34-3.24(m,2H,CH2),3.18-3.09(m,2H,CH2),2.85(s,6H,N-CH3).13C NMR(100MHz,CDCl3)δ133.9,130.1,129.4,127.2,48.2,37.5,37.4,26.9.HRMS(ESI):Cacld for C10H16NO2S2[M+H]+246.0617,found 246.0619.
4-(2-(N,N-二甲基胺基磺酰基)乙基)-2-(2-甲氧基苯基)噻唑(I-30)
原料4-乙烯基-2-(2-甲氧基苯基)噻唑(65.1mg,0.3mmol)得到化合物I-30(65.2mg,0.20mmol,67%),产物为棕色固体,熔点69-70℃。1H NMR(400MHz,CDCl3)δ8.38(dd,J=7.8,1.5Hz,1H,Ar-H),7.41-7.36(m,1H,Ar-H),7.10-7.06(m,2H,Ar-H),7.03(d,J=8.3Hz,1H,Ar-H),4.01(s,3H,O-CH3),3.49-3.45(m,2H,CH2),3.32-3.28(m,2H,CH2),2.85(s,6H,N-CH3).13C NMR(100MHz,CDCl3)δ162.4,156.4,151.7,130.8,128.3,122.1,121.0,115.7,111.4,55.6,48.0,37.4,25.5.HRMS(ESI):Cacld for C14H19N2O3S2[M+H]+327.0832,found 327.0836.
(1R,2S,5R)-2-异丙基-5-甲基环己基-4-(2-(N,N-二甲基胺基磺酰基)乙基)苯甲酸酯(I-31)原料(1R,2S,5R)-2-异丙基-5-甲基环己基-4-乙烯基苯甲酸酯(85.9mg,0.3mmol)得到化合物I-31(76.0mg,0.19mmol,64%),产物为黄色油状物。1H NMR(400MHz,CDCl3)δ8.00(d,J=8.2Hz,2H,Ar-H),7.30(d,J=8.2Hz,2H,Ar-H),4.92(td,J=10.9,4.4Hz,1H,O-CH),3.18(m,4H,CH2),2.88(s,6H,N-CH3),2.15-2.09(m,1H,CH),1.98-1.90(m,1H,CH),1.75-1.72(m,2H,CH2),1.60-1.52(m,2H,CH2),1.16-1.07(m,2H,CH2),0.94-0.90(m,6H,CH3),0.79(d,J=7.0Hz,3H,CH3).13C NMR(100MHz,CDCl3)δ165.7,143.2,130.1,129.6,128.4,74.9,49.1,47.2,41.0,37.4,34.3,31.4,29.3,26.5,23.6,22.1,20.8,16.6.HRMS(ESI):Cacld for C21H34NO4S[M+H]+396.2203,found 396.2206.
(3aR,4R,6R,6aR)-2,2-二甲基-6-(1,6-二氢-6-氧代-9h-嘌呤-9-基)四氢呋喃[3,4-d][1,3]二氧醇-4-基)甲基-4-(2-(N,N-二甲基胺基磺酰基)乙基)苯甲酸酯(I-32)
原料((3aR,4R,6R,6aR)-2,2-二甲基-6-(6-氧代-1,6-二氢-9h-嘌呤-9-基)四氢呋喃[3,4-d][1,3]二氧醇-4-基)-甲基-4-乙烯基苯甲酸酯(117.1mg,0.3mmol)得到化合物I-32(71.3mg,0.14mmol,48%),产物为黄色固体,熔点64-65℃。1H NMR(400MHz,CDCl3)δ7.99(d,J=8.2Hz,2H,Ar-H),7.33(d,J=8.2Hz,2H,Ar-H),5.95(d,J=3.7Hz,1H,O-CH),5.49(d,J=2.4Hz,1H,O-CH),4.63(d,J=3.7Hz,1H,O-CH),4.38-4.32(m,2H,CH2),4.13-4.07(m,2H,CH2),3.36-3.07(m,4H,CH2),2.89(s,6H,N-CH3),1.56(s,3H,CH3),1.42(s,3H,CH3),1.32(s,3H,CH3),1.27(s,3H,CH3).13C NMR(100MHz,CDCl3)δ164.9,144.2,130.3,128.7,128.3,112.4,109.4,105.1,83.4,79.9,76.6,72.6,67.3,49.0,37.4,29.4,26.8,26.7,26.2,25.2.HRMS(ESI):Cacld for C23H34NO9S[M+H]+500.1949,found 500.1956.
(8R,9S,13S,14S)-6,7,8,9,11,12,13,14,15,16-十二氢-13-甲基-3-(2-(N,N-二甲基胺基磺酰基)乙基)-17-羰基-环戊[a]菲酮(I-33)
原料(8R,9S,13S,14S)-6,7,8,9,11,12,13,14,15,16-十二氢-13-甲基-3-乙烯基-17-羰基-环戊[a]菲酮(84.1mg,0.3mmol)得到化合物I-33(104.0mg,0.27mmol,89%),产物为黄色固体,熔点85-86℃。1H NMR(400MHz,CDCl3)δ7.93(d,J=1.7Hz,1H,Ar-H),7.43(dt,J=15.7,5.0Hz,2H,Ar-H),3.17(s,4H,CH2),2.90(s,6H,N-CH3),2.89-2.86(m,2H,CH2),2.61-2.57(m,1H,CH),2.53(dd,J=18.7,8.6Hz,1H,CH),2.38-2.30(m,1H,CH),2.14-2.02(m,4H,CH2),1.73-1.49(m,6H,CH2),0.93(s,3H,CH3).13C NMR(100MHz,CDCl3)δ145.0,136.9,134.2,132.6,126.8,126.0,77.2,50.4,49.2,47.6,43.2,39.3,37.5,35.6,31.2,28.7,25.0,24.4,21.4,13.6.HRMS(ESI):Cacld for C22H32NO3S[M+H]+390.2097,found390.2099.
N-(4-(2-(N,N-二甲基胺基磺酰基)乙基)苯甲酰基)-L-苯丙氨酸基-L-亮氨酸苄脂(I-34)
原料N-(4-乙烯基苯甲酰基)-L-苯丙氨酸基-L-亮氨酸苄脂(149.5mg,0.3mmol)得到化合物I-34(78.0mg,0.13mmol,42%),产物为白色固体,熔点138-139℃。1H NMR(400MHz,CDCl3)δ7.67(d,J=8.0Hz,2H,Ar-H),7.38-7.32(m,5H,Ar-H),7.27-7.23(m,7H,Ar-H),6.89(d,J=7.4Hz,1H,NH),6.39(d,J=7.8Hz,1H,NH),5.19-5.12(m,2H,O-CH2),4.90(dd,J=6.9Hz,2.9Hz,1H,NH-CH),4.60-4.52(m,1H,NH-CH),3.23-3.10(m,6H,Ar-CH2+SO2-CH2),2.87(s,6H,N-CH3),1.62-1.55(m,1H,CH),1.54-1.43(m,2H,CH2),0.83(d,J=6.1Hz,6H,CH3).13C NMR(100MHz,CDCl3)δ172.1,170.7,166.7,142.3,136.4,135.3,132.5,129.5,128.7,128.7,128.5,128.3,127.6,127.1,67.1,54.6,51.2,49.2,41.3,38.4,37.5,29.2,24.8,22.7,21.9.HRMS(ESI):Cacld for C33H42N3O6S[M+H]+608.2789,found608.2796.
N-(2-(2-(3,5-二溴-4-甲氧基苯基)乙酰氨基)乙基)-4-(2-(N,N-二甲基胺基磺酰基)乙基)苯甲酰胺(I-35)
原料N-(2-(2-(3,5-二溴-4-甲氧基苯基)乙酰氨基)乙基)-4-乙烯基苯甲酰胺(149.5mg,0.3mmol)得到化合物I-35(61.7mg,0.10mmol,34%),产物为白色固体,熔点162-163℃。
1H NMR(400MHz,DMSO-d6)δ8.47(s,1H,NH),8.24(s,1H,NH),7.78(d,J=7.7Hz,2H,Ar-H),7.54(s,2H,Ar-H),7.40(d,J=7.6Hz,2H,Ar-H),3.77(s,3H,O-CH3),3.41(s,2H,Ar-CH2),3.35(d,J=16.7Hz,4H,CH2),3.24-3.22(m,2H,CH2),3.09-3.00(m,2H,CH2),2.79(s,6H,N-CH3).13C NMR(100MHz,DMSO-d6)δ170.1,166.6,152.4,142.2,136.2,133.8,133.2,128.9,127.8,117.4,60.8,47.7,41.0,39.0,37.5,28.8.HRMS(ESI):Cacld forC22H28Br2N3O5S[M+H]+604.0111,found 604.0115.
实施例2 磺酰胺I-36~I-41的合成
将1.0当量的烯烃A与1.0-5.0当量的脂肪胺基磺酰氯B、0.2-2.0mmol%的光催化剂[Ir(dF(CF3)ppy)2(dtbbpy)]PF6、1.0-5.0当量的汉斯酯、0.2-1.0当量4-甲基苯硫酚、2-5mL乙腈加入10mL Schlenk管,通过双排管,氩气抽放气3-5次,在15W的465~475nm蓝光照射下反应3~12小时,加入饱和NaCl溶液和二氯甲烷萃取,有机层干燥,真空减压脱溶,柱层析得到脂肪胺磺酰基环化产物纯品。
2-(4-甲基苯基)-甲基胺基磺酰乙烷(I-36)
原料4-甲基苯乙烯(35.5mg,0.3mmol)得到化合物I-36(40.1mg,0.19mmol,63%),产物为白色固体,熔点89-90℃。1H NMR(400MHz,CDCl3)δ7.17-7.10(m,4H,Ar-H),3.98(d,J=4.8Hz,1H,NH),3.31-3.23(m,2H,CH2),3.08(dd,J=9.6,6.3Hz,2H,CH2),2.70(d,J=5.3Hz,3H,NH-CH3),2.33(s,3H,Ar-CH3).13C NMR(100MHz,CDCl3)δ136.7,134.8,129.6,128.2,52.4,29.5,29.4,21.0.HRMS(ESI):Cacld for C10H16NO2S[M+H]+214.0896,found214.0897.
1-(4-甲基苯乙基)磺酰基吡咯烷(I-37)
原料4-甲基苯乙烯(35.5mg,0.3mmol)得到化合物I-37(68.4mg,0.27mmol,90%),产物为白色固体,熔点99-100℃。1H NMR(400MHz,CDCl3)δ7.16-7.08(m,4H,Ar-H),3.38-3.32(m,4H,N-CH2),3.23-3.16(m,2H,CH2),3.12-3.05(m,2H,CH2),2.33(s,3H,CH3),1.93-1.87(m,4H,NCH2-CH2).13C NMR(100MHz,CDCl3)δ136.5,135.2,129.5,128.3,50.9,47.7,29.1,25.9,21.0.HRMS(ESI):Cacld for C13H20NO2S[M+H]+254.1209,found 254.1211.
1-(4-甲基苯乙基)磺酰基哌啶(I-38)
原料4-甲基苯乙烯(35.5mg,0.3mmol)得到化合物I-38(64.5mg,0.24mmol,80%),产物为白色固体,熔点101-103℃。1H NMR(400MHz,CDCl3)δ7.11(q,J=8.2Hz,4H,Ar-H),3.24(t,J=4.3Hz,4H,N-CH2),3.12-3.07(m,4H,CH2),2.33(s,3H,Ar-CH3),1.69-1.61(m,4H,NCH2-CH2),1.58-1.55(m,2H,NCH2CH2-CH2).13C NMR(100MHz,CDCl3)δ136.5,135.2,129.5,128.3,50.8,46.6,46.5,28.9,25.7,23.8,21.0.HRMS(ESI):Cacld for C14H22NO2S[M+H]+268.1366,found 268.1367.
1-(4-甲基苯乙基)磺酰基哌啶(I-39)
原料4-甲基苯乙烯(35.5mg,0.3mmol)得到化合物I-39(73.5mg,0.27mmol,91%),产物为白色固体,熔点141-142℃。1H NMR(400MHz,CDCl3)δ7.17-7.08(m,4H,Ar-H),3.74(t,J=4.1Hz,4H,O-CH2),3.26(t,J=3.9Hz,4H,N-CH2),3.17-3.12(m,2H,CH2),3.12-3.06(m,2H,CH2),2.33(s,3H,Ar-H).13C NMR(100MHz,CDCl3)δ136.7,134.8,129.6,128.3,66.6,50.4,45.8,28.8,21.1.HRMS(ESI):Cacld for C13H20NO3S[M+H]+270.1158,found270.1156.
5-(2-甲基胺基磺酰基乙基)-N-Boc吲哚(I-40)
原料5-乙烯基-N-Boc吲哚(73.3mg,0.3mmol)得到化合物I-40(75.1mg,0.22mmol,74%),产物为无色油状物。1H NMR(400MHz,CDCl3)δ8.01(d,J=8.1Hz,1H,Ar-H),7.52(d,J=3.5Hz,1H,Ar-H),7.34(s,1H,Ar-H),7.09(dd,J=8.5,1.4Hz,1H,Ar-H),6.44(d,J=3.7Hz,1H,Ar-H),4.07-3.98(m,1H,NH),3.26(dd,J=9.8,5.6Hz,2H,CH2),3.13(dd,J=9.8,5.8Hz,2H,CH2),2.61(d,J=5.3Hz,3H,N-CH3),1.59(s,9H,CH3).13C NMR(100MHz,CDCl3)δ149.6,134.2,132.1,131.0,126.6,124.5,120.5,115.5,107.0,83.9,52.6,29.9,29.3,28.2.HRMS(ESI):Cacld for C16H23N2O4S[M+H]+339.1373,found 339.1375.
5-(2-(1-吡咯烷)磺酰基乙基)-N-Boc吲哚(I-41)
原料5-乙烯基-N-Boc吲哚(73.3mg,0.3mmol)得到化合物I-41(81.8mg,0.22mmol,72%),产物为白色固体,熔点112-113℃。1H NMR(400MHz,CDCl3)δ8.08(d,J=8.2Hz,1H,Ar-H),7.59(d,J=3.6Hz,1H,Ar-H),7.40(d,J=1.1Hz,1H,Ar-H),7.16(dd,J=8.5,1.6Hz,1H,Ar-H),6.52(d,J=3.7Hz,1H,Ar-H),3.36(t,J=6.7Hz,4H,CH2),3.29-3.16(m,4H,CH2),1.94-1.85(m,4H,CH2),1.67(s,9H,CH3).13C NMR(100MHz,CDCl3)δ149.7,134.1,132.6,131.0,126.5,124.6,120.5,115.4,107.0,83.8,51.2,47.7,29.5,28.2,25.9.HRMS(ESI):Cacld for C19H27N2O4S[M+H]+379.1686,found 379.1689.
以上详细描述了本发明的优选实施方式,但是,本发明并不限于此。在本发明的技术构思范围内,可以对本发明的技术方案进行多种简单变型,包括各个技术特征以任何其它的合适方式进行组合,这些简单变型和组合同样应当视为本发明所公开的内容,均属于本发明的保护范围。
Claims (3)
1.一种由脂肪胺基磺酰氯在光催化条件下制备烷基磺酰胺的方法,其特征在于取代烯烃A在一定溶剂中,氩气氛围,光催化剂、还原剂和硫酚共同作用,蓝光源照射下与脂肪胺基磺酰氯B发生自由基加成和硫酚协调氢原子转移的氢化磺酰胺化反应制得磺酰胺I:
式中:R1为:苯基、4-甲基苯基、4-叔丁基苯基、4-甲氧基苯基、4-乙酰氧基苯基、4-甲酸酯基苯基、4-三氟甲基苯基、4-硝基苯基、4-氟苯基、4-氯苯基、4-溴苯基,4-羟基苯基、4-(N-Boc-胺基)苯基、2-甲基苯基、2-溴苯基、3-溴苯基、2,3,4,5,6-五氟苯基、取代萘环、喹啉环、噻吩环、苯并噻唑环、吲哚环、硫醚、酚噻唑酸衍生物、薄荷醇衍生物、双丙酮-D-葡萄糖衍生物、雌酚酮衍生物、H-Phe-Leu-OBzl衍生物或紫草素衍生物;R2为:甲基或苯基;R3为:甲基;R4和R5分别独立的为:氢、甲基、1-吗啉基、1-哌啶基或1-吡咯基;
反应中烯烃(A)、光催化剂、硫酚、脂肪胺基磺酰氯(B)、还原剂的摩尔比是1∶0.002-0.2∶0.1-1∶1-5∶1-5;
反应温度范围为-30-80℃;
反应时间为0.5-48小时;
所使用的还原剂为N,N-二异丙基乙胺或汉斯酯;
所使用的硫酚为4-甲氧基苯硫酚、苯硫酚、4-甲氧基苯硫酚或4-硝基苯硫酚;
所使用的有机溶剂选自乙醇、甲醇、环己烷、正己烷、正戊烷、正庚烷、石油醚、乙醚、四氢呋喃、二氯甲烷、三氯甲烷、四氯化碳、1,2-二氯乙烷和乙腈中的至少一种;
光催化剂为[Ir{dF(CF3)ppy}2(dtbbpy)]PF6,[Ir(dtbbpy)(ppy)2]PF6,Eosin Y,Ru(bpy)3(PF6)2,Ir(ppy)3或Mes-Acr+。
2.权利要求1所述的由脂肪胺基磺酰氯在光催化条件下制备烷基磺酰胺的方法,其特征在于反应温度为20-50℃,反应时间为1-36小时,还原剂为汉斯酯,硫酚为4-甲基苯硫酚,有机溶剂为乙腈,光催化剂为[Ir{dF(CF3)ppy}2(dtbbpy)]PF6。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110799183.8A CN115611781B (zh) | 2021-07-15 | 2021-07-15 | 一种由脂肪胺基磺酰氯制备烷基磺酰胺的新方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110799183.8A CN115611781B (zh) | 2021-07-15 | 2021-07-15 | 一种由脂肪胺基磺酰氯制备烷基磺酰胺的新方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN115611781A true CN115611781A (zh) | 2023-01-17 |
CN115611781B CN115611781B (zh) | 2024-03-26 |
Family
ID=84856006
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202110799183.8A Active CN115611781B (zh) | 2021-07-15 | 2021-07-15 | 一种由脂肪胺基磺酰氯制备烷基磺酰胺的新方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN115611781B (zh) |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111217736A (zh) * | 2020-02-12 | 2020-06-02 | 陕西科技大学 | 一种光催化下2-酰基吲哚化合物的合成方法 |
-
2021
- 2021-07-15 CN CN202110799183.8A patent/CN115611781B/zh active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111217736A (zh) * | 2020-02-12 | 2020-06-02 | 陕西科技大学 | 一种光催化下2-酰基吲哚化合物的合成方法 |
Non-Patent Citations (3)
Title |
---|
""Photoredox-Catalyzed Generation of Sulfamyl Radicals: Sulfonamidation of Enol Silyl Ether with Chlorosulfonamide"", 《J. ORG. CHEM.》, vol. 84, pages 13897 - 13907 * |
SANDRINE M. HELL等: ""Silyl Radical-Mediated Activation of Sulfamoyl Chlorides Enables Direct Access to Aliphatic Sulfonamides from Alkenes"", 《J. AM. CHEM. SOC.》, vol. 142, pages 720 - 725 * |
ZHANG MINGJUN等: ""Generation and precise control of sulfonyl radicals: visible-light-activated redox-neutral formation of sulfonates and sulfonamides"", 《ORG. CHEM. FRONT.》, vol. 8, pages 961 - 967 * |
Also Published As
Publication number | Publication date |
---|---|
CN115611781B (zh) | 2024-03-26 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US7595338B2 (en) | Process for preparing 3,3-disubstituted oxindoles and thio-oxindoles | |
US7838550B2 (en) | Selective N-sulfonylation of 2-amino fluoro- and trifluoroalkyl substituted alcohols | |
US7582755B2 (en) | Cyanopyrrole-containing cyclic carbamate and thiocarbamate biaryls and methods for preparing the same | |
KR20080093126A (ko) | 술폰아미드 치환된 알코올 및 이의 중간체의 제조 방법 | |
HU226881B1 (en) | Efficient enantioselective addition reaction using an organozinc reagent | |
WO2011000212A1 (zh) | 依泽替米贝的制备方法及其中间体 | |
CN115611781A (zh) | 一种由脂肪胺基磺酰氯制备烷基磺酰胺的新方法 | |
Kerr et al. | Enantioselective N-heterocyclic carbene catalyzed formal [3+ 2] cycloaddition using α-aroyloxyaldehydes and oxaziridines | |
Chen et al. | Chiral N-phosphonyl imine chemistry: asymmetric additions of malonate-derived enolates to chiral N-phosphonyl imines for the synthesis of β-aminomalonates | |
Tranchant et al. | Reaction of vinyl triflates of α-keto esters with primary amines: Efficient synthesis of aziridine carboxylates | |
CN115286578A (zh) | 一种含三氟甲基的吡唑化合物的制备方法 | |
Chen et al. | A cascade process for the synthesis of gem-difluoromethylene compounds | |
US20100160681A1 (en) | Chiral phosphoramides, chiral N-phosphonimines and methods for forming the same | |
CN110734378B (zh) | 一种高化学及立体选择性制备手性烯丙基胺类化合物的方法 | |
CN110041365B (zh) | 吡咯啉类手性双膦配体及其制备方法和应用 | |
CN109851599A (zh) | 一种2-氨基苯并呋喃化合物的制备方法 | |
CN114988976B (zh) | 一种有机催化Nazarov环化合成手性环戊烯酮类化合物的方法 | |
Malhotra et al. | Divergent asymmetric synthesis of hexahydrobenzophenanthridine dopamine D1 agonists, A-86929, and dihydrexidine | |
JP2005053781A (ja) | 光学活性な3−(n−メチルアミノ)−1−(2−チエニル)−プロパン−1−オールの製造方法 | |
Tang et al. | Metal-free synthesis of N-vinyl sulfoximines via DABCO-participated Michael addition of terminal carbonyl alkynes with N-chlorosulfoximines | |
CN117447356A (zh) | 一种环戊烯酮类衍生物及其合成方法和应用 | |
JP2024516199A (ja) | バルベナジンの合成方法 | |
CN114539121A (zh) | 一种光促进的由磺酰氯制备磺酸盐和磺酰胺的新方法 | |
CN117209457A (zh) | 一种α-手性脒化合物的合成 | |
WO2021226149A1 (en) | Synthesis of optically active indoline derivatives via ruthenium(ii)-catalyzed enantioselective c-h functionalization |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |