CN110372628A - Interior sulfamide compound and preparation method thereof - Google Patents
Interior sulfamide compound and preparation method thereof Download PDFInfo
- Publication number
- CN110372628A CN110372628A CN201910616230.3A CN201910616230A CN110372628A CN 110372628 A CN110372628 A CN 110372628A CN 201910616230 A CN201910616230 A CN 201910616230A CN 110372628 A CN110372628 A CN 110372628A
- Authority
- CN
- China
- Prior art keywords
- alkyl
- interior
- aryl
- optionally
- hydrogen
- 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
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- -1 sulfamide compound Chemical class 0.000 title claims description 67
- 229940124530 sulfonamide Drugs 0.000 claims abstract description 30
- 238000006243 chemical reaction Methods 0.000 claims abstract description 29
- 150000003456 sulfonamides Chemical class 0.000 claims abstract description 26
- 239000007800 oxidant agent Substances 0.000 claims abstract description 21
- 230000001590 oxidative effect Effects 0.000 claims abstract description 20
- 239000003054 catalyst Substances 0.000 claims abstract description 15
- 150000004698 iron complex Chemical class 0.000 claims abstract description 12
- JNGZXGGOCLZBFB-IVCQMTBJSA-N compound E Chemical compound N([C@@H](C)C(=O)N[C@@H]1C(N(C)C2=CC=CC=C2C(C=2C=CC=CC=2)=N1)=O)C(=O)CC1=CC(F)=CC(F)=C1 JNGZXGGOCLZBFB-IVCQMTBJSA-N 0.000 claims abstract description 10
- NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical class NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000003960 organic solvent Substances 0.000 claims abstract description 9
- 125000005463 sulfonylimide group Chemical group 0.000 claims abstract description 8
- 239000000463 material Substances 0.000 claims abstract description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 42
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 34
- 125000000217 alkyl group Chemical group 0.000 claims description 26
- 239000001257 hydrogen Substances 0.000 claims description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims description 24
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 24
- 125000003118 aryl group Chemical group 0.000 claims description 22
- 125000003342 alkenyl group Chemical group 0.000 claims description 20
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 19
- 125000003545 alkoxy group Chemical group 0.000 claims description 14
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 13
- 239000003446 ligand Substances 0.000 claims description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- 125000004414 alkyl thio group Chemical group 0.000 claims description 12
- 125000001769 aryl amino group Chemical group 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 125000003107 substituted aryl group Chemical group 0.000 claims description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 8
- 125000003282 alkyl amino group Chemical group 0.000 claims description 8
- 239000002994 raw material Substances 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- 229910052742 iron Inorganic materials 0.000 claims description 7
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 6
- YCOXTKKNXUZSKD-UHFFFAOYSA-N as-o-xylenol Natural products CC1=CC=C(O)C=C1C YCOXTKKNXUZSKD-UHFFFAOYSA-N 0.000 claims description 6
- 238000004440 column chromatography Methods 0.000 claims description 6
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 6
- SNHMUERNLJLMHN-UHFFFAOYSA-N iodobenzene Chemical compound IC1=CC=CC=C1 SNHMUERNLJLMHN-UHFFFAOYSA-N 0.000 claims description 6
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 6
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical class ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 4
- FTSSFFOOJBWGQL-UHFFFAOYSA-N CC(C(=O)O)(C(=O)O)C.IC1=CC=CC=C1 Chemical compound CC(C(=O)O)(C(=O)O)C.IC1=CC=CC=C1 FTSSFFOOJBWGQL-UHFFFAOYSA-N 0.000 claims description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- PCRAJOWHMTYSKR-UHFFFAOYSA-N iodobenzene;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.IC1=CC=CC=C1 PCRAJOWHMTYSKR-UHFFFAOYSA-N 0.000 claims description 4
- 150000002790 naphthalenes Chemical class 0.000 claims description 4
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 claims description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- DORMTBIPKNPJPY-UHFFFAOYSA-N acetic acid;iodobenzene Chemical compound CC(O)=O.IC1=CC=CC=C1 DORMTBIPKNPJPY-UHFFFAOYSA-N 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 3
- 238000004821 distillation Methods 0.000 claims description 3
- 150000002505 iron Chemical class 0.000 claims description 3
- 238000001953 recrystallisation Methods 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- QCSDUECDSLGYSD-UHFFFAOYSA-N C(C1=CC=CC=C1)(=O)O.IC1=CC=CC=C1 Chemical compound C(C1=CC=CC=C1)(=O)O.IC1=CC=CC=C1 QCSDUECDSLGYSD-UHFFFAOYSA-N 0.000 claims description 2
- BQSXIOTYUJEEML-UHFFFAOYSA-N C1(=CC=CC=C1)I.[O] Chemical compound C1(=CC=CC=C1)I.[O] BQSXIOTYUJEEML-UHFFFAOYSA-N 0.000 claims description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 claims description 2
- 150000001450 anions Chemical class 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 229910001914 chlorine tetroxide Inorganic materials 0.000 claims description 2
- 125000001072 heteroaryl group Chemical group 0.000 claims description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 2
- 150000002825 nitriles Chemical class 0.000 claims description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Chemical compound [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 230000017260 vegetative to reproductive phase transition of meristem Effects 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- GNHQSAUHXKRQMC-UHFFFAOYSA-N benzene;chlorine Chemical compound [Cl].C1=CC=CC=C1 GNHQSAUHXKRQMC-UHFFFAOYSA-N 0.000 claims 1
- 238000001514 detection method Methods 0.000 claims 1
- AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 claims 1
- 238000000746 purification Methods 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 13
- 238000003786 synthesis reaction Methods 0.000 abstract description 8
- 230000001988 toxicity Effects 0.000 abstract description 2
- 231100000419 toxicity Toxicity 0.000 abstract description 2
- 238000005580 one pot reaction Methods 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 106
- 238000005160 1H NMR spectroscopy Methods 0.000 description 34
- 239000007787 solid Substances 0.000 description 32
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 22
- 239000011734 sodium Substances 0.000 description 21
- 241000790917 Dioxys <bee> Species 0.000 description 18
- XGYCWCIGCYGQFU-UHFFFAOYSA-N 1,2-thiazolidine 1,1-dioxide Chemical compound O=S1(=O)CCCN1 XGYCWCIGCYGQFU-UHFFFAOYSA-N 0.000 description 13
- 239000002808 molecular sieve Substances 0.000 description 11
- 239000000758 substrate Substances 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 7
- 229960002262 profenamine Drugs 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- WEVYAHXRMPXWCK-FIBGUPNXSA-N acetonitrile-d3 Chemical compound [2H]C([2H])([2H])C#N WEVYAHXRMPXWCK-FIBGUPNXSA-N 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 5
- 239000012065 filter cake Substances 0.000 description 4
- CKFMJXZQTNRXGX-UHFFFAOYSA-L iron(2+);diperchlorate Chemical compound [Fe+2].[O-]Cl(=O)(=O)=O.[O-]Cl(=O)(=O)=O CKFMJXZQTNRXGX-UHFFFAOYSA-L 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 3
- 125000005605 benzo group Chemical group 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000007363 ring formation reaction Methods 0.000 description 3
- 239000012266 salt solution Substances 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 125000000565 sulfonamide group Chemical group 0.000 description 3
- CRUILBNAQILVHZ-UHFFFAOYSA-N 1,2,3-trimethoxybenzene Chemical compound COC1=CC=CC(OC)=C1OC CRUILBNAQILVHZ-UHFFFAOYSA-N 0.000 description 2
- 238000004293 19F NMR spectroscopy Methods 0.000 description 2
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 2
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 2
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 2
- QFZHTRYMJCITDV-UHFFFAOYSA-N 3-phenyl-1,2-thiazolidine 1,1-dioxide Chemical compound N1S(=O)(=O)CCC1C1=CC=CC=C1 QFZHTRYMJCITDV-UHFFFAOYSA-N 0.000 description 2
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- DYUQAZSOFZSPHD-UHFFFAOYSA-N Phenylpropyl alcohol Natural products CCC(O)C1=CC=CC=C1 DYUQAZSOFZSPHD-UHFFFAOYSA-N 0.000 description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 description 2
- 238000005576 amination reaction Methods 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 2
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- CZSRXHJVZUBEGW-UHFFFAOYSA-N 1,2-thiazolidine Chemical compound C1CNSC1 CZSRXHJVZUBEGW-UHFFFAOYSA-N 0.000 description 1
- GVYVHZKTSVDMNT-UHFFFAOYSA-N 2,3-dihydro-1,2-benzothiazole 1,1-dioxide Chemical compound C1=CC=C2S(=O)(=O)NCC2=C1 GVYVHZKTSVDMNT-UHFFFAOYSA-N 0.000 description 1
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 1
- HQNSWBRZIOYGAW-UHFFFAOYSA-N 2-chloro-n,n-dimethylpyridin-4-amine Chemical compound CN(C)C1=CC=NC(Cl)=C1 HQNSWBRZIOYGAW-UHFFFAOYSA-N 0.000 description 1
- XDLKHEFKZQJAEV-UHFFFAOYSA-N 3,3-dimethyl-1,2-thiazolidine 1,1-dioxide Chemical compound CC1(C)CCS(=O)(=O)N1 XDLKHEFKZQJAEV-UHFFFAOYSA-N 0.000 description 1
- ULZOVNGHPDAGMF-UHFFFAOYSA-N 3-methyl-1,2-thiazolidine 1,1-dioxide Chemical compound CC1CCS(=O)(=O)N1 ULZOVNGHPDAGMF-UHFFFAOYSA-N 0.000 description 1
- WZOKMILQIPCVQJ-UHFFFAOYSA-N 3-methyl-2,3-dihydro-1,2-benzothiazole 1,1-dioxide Chemical compound C1=CC=C2C(C)NS(=O)(=O)C2=C1 WZOKMILQIPCVQJ-UHFFFAOYSA-N 0.000 description 1
- ADXOWPSNHDMYNN-UHFFFAOYSA-N 3-methyl-4,5-dihydro-1,2-thiazole 1,1-dioxide Chemical compound CC1=NS(=O)(=O)CC1 ADXOWPSNHDMYNN-UHFFFAOYSA-N 0.000 description 1
- DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical compound C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 description 1
- 238000005698 Diels-Alder reaction Methods 0.000 description 1
- 238000006617 Intramolecular Heck reaction Methods 0.000 description 1
- 241000288047 Phasianus colchicus Species 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
- NVJHHSJKESILSZ-UHFFFAOYSA-N [Co].N1C(C=C2N=C(C=C3NC(=C4)C=C3)C=C2)=CC=C1C=C1C=CC4=N1 Chemical compound [Co].N1C(C=C2N=C(C=C3NC(=C4)C=C3)C=C2)=CC=C1C=C1C=CC4=N1 NVJHHSJKESILSZ-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 238000005865 alkene metathesis reaction Methods 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- OREAFAJWWJHCOT-UHFFFAOYSA-N dimethylmalonic acid Chemical compound OC(=O)C(C)(C)C(O)=O OREAFAJWWJHCOT-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052741 iridium Inorganic materials 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- 150000003951 lactams Chemical group 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- 239000003863 metallic catalyst Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 230000005311 nuclear magnetism Effects 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000005546 pivalic acid group Chemical group 0.000 description 1
- 125000006238 prop-1-en-1-yl group Chemical group [H]\C(*)=C(/[H])C([H])([H])[H] 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- DNGMYXZLJGHHOM-UHFFFAOYSA-N thiazinane 1,1-dioxide Chemical compound O=S1(=O)CCCCN1 DNGMYXZLJGHHOM-UHFFFAOYSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 229940030010 trimethoxybenzene Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 235000020681 well water Nutrition 0.000 description 1
- 239000002349 well water Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
- C07D275/02—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
- C07D275/02—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings
- C07D275/03—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
- C07D275/04—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems
- C07D275/06—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems with hetero atoms directly attached to the ring sulfur atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D279/02—1,2-Thiazines; Hydrogenated 1,2-thiazines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
- C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
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- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention provides a kind of interior sulfamide compounds and preparation method thereof.Specific method of the invention is that catalyst C, sulfonamide B, oxidant D are added in organic solvent to react, by separating-purifying, obtain a kind of interior sulfamide compound E or it is to be detected after the reaction was completed, after adding oxidant F reaction, into isolating and purifying, interior sulfonyl imide compounds G is obtained.Catalyst needed for this method is cheap and easy to get, the low iron complex of toxicity.When using sulfonamide H, by after completion of the reaction, then being additionally added under conditions of another oxidant F according to above method, sulfonyl imide compounds in one pot process are realized.Prepared interior sulfonamide and interior sulfonyl imide compounds are widely used in pharmaceutical chemistry, materials chemistry and organic synthesis field.
Description
Technical field
The present invention relates to technical field of organic synthesis, and in particular to a kind of interior sulfamide compound and preparation method thereof.
Background technique
Sulfonamide structure skeleton is widely present in some drug macromoleculars with broad spectrum antibiotic activity, be it is a kind of very
Important structure fragment plays an important role in new drug synthesis.It is emphasized that interior sulfonamides structure has well
Water solubility and stability, be considered as lactams skeleton equivalent, and be widely used in the structural modification of drug (such as Fig. 3 institute
Show), thus in field of medicinal chemistry by the extensive concern of scientists [a) Mustafa, A.Chem.Rev.1954,54,
195–223.b)Inagaki,M.；Tsuri,T.；Jyoyama,H.； Ono,T.；Yamada,K.；Kobayashi,M.；Hori,
Y.；Arimura,A.；Yasui,K.；Ohno,K.； Kakudo,S.；Koizumi,K.；Suzuki,R.；Kato,M.；Kawai,
S.；Matsumoto,S.J.Med. Chem.2000,43,2040–2048.c)Donkor,I.O.Curr.Med.Chem.2000,
7,1171–1188.d) Wells,G.J.；Tao,M.；Josef,K.A.；Bihovsky,R.J.Med.Chem.2001,44,
3488–3503. e)Lebegue,N.；Gallet,S.；Flouquet,N.；Carato,P.；Pfeiffer,B.；Renard,
P.；Léonce,S.； Pierré,A.；Chavatte,P.；Berthelot,P.J.Med.Chem.2005,48,7363–
7373.f)Lad,N.P.； Kulkarni,S.；Sharma,R.；Mascarenhas,M.；Kulkarni,M.R.；Pandit,
S.S. Piperlongumine.Eur.J.Med.Chem.2017,126,870-878.], in addition, this class formation can also be applied
In certain heterocyclic compounds and natural products fully synthetic [a) Davison, E.C.；Fox,M.E.；Holmes, A.B.；
Roughley,S.D.；Smith,C.J.；Williams,G.M.；Davies,J.E.；Raithby,P.R.；Adams,J.P.；
Forbes,I.T.；Press,N.J.；Thompson,M.J.J.Chem.Soc.,Perkin Trans. 12002,12,1494–
1514.b)Storer,R.I.；Takemoto,T.；Jackson,P.S.；Brown,D.S.； Baxendale,I.R.；Ley,
S.V.Chem.Eur.J.2004,10,2529–2547.].The method for synthesizing this class formation at present mainly includes (1) Diels-
Alder cyclization [a) Rassadin, V.A.；Grosheva,D.S.； Tomashevskii,A.A.；Sokolov,
V.V.Chem.Heterocycl.Compd.2013,49,39–65.b) Greig,I.R.；Tozer,M.J.；Wright,
P.T.Org.Lett.2001,3,369–371.]；(2) cyclization olefin metathesis (RCM) [a) McReynolds, M.D.；
Dougherty,J.M.；Hanson,P.R.Chem.Rev.2004, 104,2239–2258.b)Karsch,S.；Freitag,
D.；Schwab,P.Metz,P.Synthesis 2004, 1696–1712.]；(3) free cyclization [Ueda, M.；Miyabe,
H.；Nishimura,A.；Miyata,O.； Takemoto,Y.；Naito,T.Org.Lett.2003,5,3835–3838.]；
(4) intramolecular Heck reaction [a) Khalifa, A.；Conway,L.；Geoghegan,K.；Evans,P.Tetrahedron
Lett.2017,58, 4559–4562.b)Laha,J.K.；Sharma,S.；Kirar,S.；Banerjee,
U.C.J.Org.Chem.2017,82,9350-9359.] etc..
Currently, the synthetic method of the interior sulfonamide backbones of catalysis is rarely reported, and it is only limitted to benzenesulfonyl azide substrate point
Amination in son synthesizes benzene sulfinyl amine structure skeleton.In recent years with the fast development of enzymic catalytic reaction, Arnold,
Fasan and Hartwig seminar reports arylsulfonyl nitrine substrate enzymatically in succession, and intramolecular amination occurs, obtains
Sulfonamide structure in the benzo of rigidity, [a) McIntosh, J.A. with good chemo-selective and enantioselectivity；
Coelho,P.S.；Farwell,C.C.；Wang,Z.J.；Lewis,J.C.；Brown, R.；Arnold,
F.H.Angew.Chem.,Int.Ed.2013,52,9309–9312.b)Hyster,T.K.； Farwell,C.C.；Buller,
A.R.；McIntosh,J.A.；Arnold,F.H.J.Am.Chem.Soc.2014, 136,15505–15508.c)Prier,
C.K.；Zhang,R.K.；Buller,A.R.；Brinkmann-Chen,S.； Arnold,F.H.Nat.Chem.2017,9,
629–634.d)Singh,R.；Bordeaux,M.；Fasan,R. ACS Catal.2014,4,546–552.e)Singh,R.；
Kolev,J.N.；Sutera,P.A.；Fasan,R.ACS Catal.2015,5,1685–1691.f)Dydio,P.；Key,
H.M.；Hayashi,H.；Clark,D.S.； Hartwig,J.F..J.Am.Chem.Soc.2017,139,1750–1753.].
Metallic catalyst Cobalt Porphyrin and iridium imines compound can also be catalyzed the inner molecular reaction of aryl sulfonic acid amides, synthesize sulfonamide in benzo
[Ruppel,J.V.； Kamble,R.M.；Zhang,X.P..Org.Lett.2007,9,4889–4892；Ichinose,M.；
Suematsu, H.；Yasutomi,Y.；Nishioka,Y.；Uchida,T.；Katsuki,T.Angew.Chem.,
Int.Ed.2011, 50,9884–9887.].In short, these methods are not easy to obtain there are catalyst structure complexity, and price is high
Your the disadvantages of, it is often more important that, the reaction substrate of these methods is all confined to arylsulfonyl nitrine substrate, and it is rigid to be only used for synthesis
Sulfonamide product in the benzo of property.
Summary of the invention
In order to solve defect of the existing technology, the object of the present invention is to provide a kind of interior sulfamide compound and its
Preparation method synthesizes interior sulfonamide and interior sulfonyl imide compounds with the new method that iron complex is catalyzed.
To achieve the above object, the interior sulfamide compound that one aspect of the present invention provides, it is characterised in that: including interior sulphur
Amides compound E and interior sulfamide compound G；
The molecular structural formula of the interior sulfamide compound E is as follows:
The molecular structural formula of the interior sulfamide compound G is as follows:
Wherein R1、R2、R3、R4、R5It is independently；N, which appoints, is derived from 0,1 or 2；
The R1Optionally from hydrogen, alkyl, alkenyl, aryl, substituted aryl, alkoxy, phenol oxygroup, alkylthio group, phenol sulfenyl,
Alkyl amine group or arylamino；
The R2Optionally from hydrogen, alkyl, alkenyl, aryl, substituted aryl, alkoxy, phenol oxygroup, alkylthio group, phenol sulfenyl,
Alkyl amine group or arylamino；
The R3Optionally from hydrogen, alkyl, alkenyl, aryl；
The R4Optionally from hydrogen, alkyl, alkenyl, aryl；
The R5Optionally from hydrogen, alkyl, alkenyl, aryl, substituted aryl, alkoxy, phenol oxygroup, alkylthio group, phenol sulfenyl,
Alkyl amine group or arylamino.
The preparation method for the interior sulfamide compound that another aspect of the present invention provides, it is characterised in that: including following step
It is rapid:
Iron complex catalyst C, stock sulfonamide B, oxidant D are added in organic solvent and are stirred to react, is passed through after reaction
Separating-purifying is crossed, interior sulfamide compound E is obtained；In raw material dosage, iron complex catalyst C, stock sulfonamide B, oxidation
The mass ratio of the material range of agent D is 0.01:1:1 to 0.5:1:5；
Obtained interior sulfamide compound E is using sulfonamide B as raw material, and reaction equation is as follows:
Alternatively, iron complex catalyst C, stock sulfonamide H, oxidant D to be added in organic solvent and be stirred to react, detect
After the reaction was completed, after adding oxidant F reaction, into isolating and purifying, interior sulfonyl imide compounds G is obtained；In raw material dosage
On, the iron complex catalyst C, stock sulfonamide H, oxidant D, oxidant F the mass ratio of the material range be 0.01:1:1:1
To 0.5:1:5:2；
Obtained interior sulfamide compound G is using sulfonamide H as raw material, and reaction equation is as follows:
Wherein R1、R2、R3、R4、R5It is independently；N, which appoints, is derived from 0,1 or 2；
The R1Optionally from hydrogen, alkyl, alkenyl, aryl, substituted aryl, alkoxy, phenol oxygroup, alkylthio group, phenol sulfenyl,
Alkyl amine group or arylamino；
The R2Optionally from hydrogen, alkyl, alkenyl, aryl, substituted aryl, alkoxy, phenol oxygroup, alkylthio group, phenol sulfenyl,
Alkyl amine group or arylamino；
The R3Optionally from hydrogen, alkyl, alkenyl, aryl；
The R4Optionally from hydrogen, alkyl, alkenyl, aryl；
The R5Optionally from hydrogen, alkyl, alkenyl, aryl, substituted aryl, alkoxy, phenol oxygroup, alkylthio group, phenol sulfenyl,
Alkyl amine group or arylamino.
The structure of the oxidant F is Ar2I(OCOCF3)2, wherein Ar2Appoint and is derived from phenyl, substituted phenyl, naphthalene, takes
The naphthalene in generation；
The iron complex catalyst C is the complex compound that molysite and ligand are formed；Wherein molysite optionally from trivalent iron salt or
Person's divalent iron salt, structural formula are Fe (X)2Or Fe (X)3；X is optionally from following anion: Cl–、Br–、 I–、AcO–、TfO–、
ClO4 –、BF4 –Or SbF6 –；Wherein ligand is appointed and is derived from such as flowering structure:Wherein
R6Appoint and is derived from hydrogen, the alkyl of C1-C6, phenyl or substituted phenyl；Wherein R7、R8、R9Independent substituent group respectively, it is identical or
Person is different；R7、R8、R9Appoint and is derived from hydrogen, the alkyl of C1-C6 or containing fluoroalkyl, aryl, heteroaryl, alkoxy, alkyl amine group, virtue
Base amino；Wherein the ratio of the amount of the substance of iron and ligand is 1:1 to 1:3；
The oxidant D is high price iodide, appoints and is derived from oxygen iodobenzene or Ar1I(OCOR)2；Wherein Ar1Appoint and is derived from phenyl, takes
Phenyl, naphthalene or the substituted naphthalene in generation；Wherein R appoints the alkyl for being derived from C1-C6 or containing fluoroalkyl.
Preferably, the ratio of the amount of the substance of the iron and ligand is 1:2.
Further, the fluoroalkyl that contains is iodobenzene acetate, trifluoroacetic acid iodobenzene, pivalic acid iodobenzene, dimethyl malonic acid
It is any in iodobenzene or benzoic acid iodobenzene.
Further, the temperature being stirred to react is 20 degrees Celsius to 120 degrees Celsius；The separating-purifying is column layer
It is any in analysis, recrystallization or distillation.
Further, the organic solvent is optionally from the combination of following solvent or solvent: acetonitrile, the tert-butyl alcohol, 1,
2- dichloroethanes, methylene chloride, tetrahydrofuran, methyl tertiary butyl ether(MTBE), dioxane, dimethyl sulfoxide, N, N '-dimethyl formyl
Amine, trifluoroethanol, benzene,toluene,xylene or chlorobenzene.
Further, the organic solvent is acetonitrile or 1,2- dichloroethanes.
In above-mentioned reaction, molecular sieve, which is added, can be improved the yield of reaction, and wherein molecular sieve is optional certainlyMolecular sieve,Molecular sieve,Molecular sieve, preferablyMolecular sieve；
The invention has the advantages that and the utility model has the advantages that
(1) this method realizes the synthesis of interior sulfamide compound using iron catalyst cheap and easy to get for the first time, reaction
It is easy to operate, reaction efficiency height, good economy performance；
(2) oxidant is added by situ, realizes one kettle way and prepare interior sulfonyl imide compounds, is interior sulfimide
Synthesis provide a kind of completely new method；
(3) the lesser iron catalyst of toxicity is used, heavy-metal residual in synthesized product and anti-can be effectively reduced
It should pollution to environment itself.
Detailed description of the invention
Fig. 1 is sulfamide compound E reactional equation schema in the present invention；
Fig. 2 is sulfamide compound G reactional equation schema in the present invention；
Fig. 3 is the representative bioactive molecule structure containing interior sulfonamide backbones.
Specific embodiment
By following detailed description it will be further appreciated that the features and advantages of the invention.Provided embodiment is only pair
The explanation of the method for the present invention, remaining content without limiting the invention in any way announcement.
Embodiment 1: using phenylpropyl alcohol sulfonamide as standard substrate, to the reaction condition of the interior sulfonamide synthesis of iron catalysis
It is studied:
Wherein, footnote a is that reaction is operated at 60 degrees Celsius；Footnote b indicates reaction that molecular sieve is not added；Wherein [Fe] is
Molysite；Shown in ligand structure L1-L7 as drawn by table；The relative molecular weight that mol% refers to, equiv represent equivalent, and alkali represents normal
With inorganic base, solvent refers to organic solvent, volume 2mL；Wherein DMF is N, and N '-dimethyl formamide, MeCN is second
Nitrile, DCE 1,2- dichloroethanes, Isosorbide-5-Nitrae-dioxane are dioxane, toluene is toluene.Wherein, ligand refers to multiple tooth nitrogen
Ligand, oxidant are oxidants, and yield refers to total nuclear-magnetism yield of interior sulfonamide and interior sulfimide, with equal trimethoxy-benzene
For internal standard compound.PhI(OAc)2It is iodobenzene acetate, PhI (OCOCF3)2It is trifluoroacetic acid iodobenzene, PhI (DMM) is dimethyl malonic acid
Iodobenzene, PhI (OPiv)2It is pivalic acid iodobenzene.
3- phenylisothiazole alkane -1,1- dioxy [3-Phenylisothiazolidine 1,1-dioxide]:
White solid,1H NMR(400MHz,CDCl3)δ7.54–7.31(m,5H),4.76–4.70(m, 2H),3.44–
3.29 (m, 1H), 3.20 (m, J=12.6,10.6,7.6Hz, 1H), 2.80-2.73 (m, 1H), 2.45-2.34 (m, 1H)
Embodiment 2:
3- (4- aminomethyl phenyl) isothiazolidine -1,1- dioxy [3- (4-Tolyl) isothiazolidine 1,1-
dioxide]:
Ferrous perchlorate (5.1mg, 0.02mmol) and ligand L 2 (8.2mg, 0.04mmol) are first weighed in 4mL reaction flask
In, 1.0mL acetonitrile is added and is dissolved, stirs 30 minutes, after complexes ira situ, weighs at room temperatureMolecular sieve
(50.0mg), pivalic acid iodobenzene (163.8mg, 0.4mmol) and to first class phenylpropyl alcohol sulfonamide substrate (42.3mg, 0.2mmol) add
Enter in reaction system, add the dissolution of 1.0mL acetonitrile, at 80 DEG C, reacts 2h, filtering, the appropriate saturated sodium bicarbonate of filter cake
Washing, water phase are extracted with dichloromethane 3 times (3 × 10mL), merge organic phase, and saturated common salt is washed, at anhydrous sodium sulfate drying
It manages, after desolventizing, column chromatography for separation (methylene chloride/petroleum ether=1:1~methylene chloride) obtains interior sulfonamide 3- (4- methylbenzene
Base) isothiazolidine 1,1- dioxy (33.7mg, 80%), white solid.1H NMR(400MHz, CDCl3) δ 7.29 (d, J=
8.1Hz, 2H), 7.19 (d, J=7.9Hz, 2H), 4.70 (dt, J=9.0,5.9Hz, 1H), 4.43 (br s, 1H), 3.36
(ddd, J=12.1,8.0,3.8Hz, 1H), 3.21 (ddd, J=12.7,10.3,7.6Hz, 1H), 2.75 (dtd, J=11.0,
7.0,3.8Hz,1H),2.46–2.37(m,1H),2.35(s,3H).
Embodiment 3:
3- (4- methoxyphenyl) isothiazolidine -1,1- dioxy [3- (4-Methoxyphenyl) isothiazolidine
1,1-dioxide]
White solid；Yield 86%；1H NMR(400MHz,CDCl3) δ 7.32 (d, J=8.8Hz 2H), 6.90 (d, J=
8.8Hz 2H),4.79–4.63(m,1H),4.50(br s,1H),3.81(s,3H),3.45–3.32 (m,1H),3.25–3.17
(m,1H),2.76–2.68(m,1H),2.44–2.34(m,1H)；13C NMR(100 MHz,CDCl3)δ159.8,132.0,
127.5,114.5,58.0,55.5,48.5,32.4；HRMS(ESI+) calc'd for C10H13NNaO3S[M+Na]+:
250.0508,found 250.0513.
3- phenylisothiazole alkane -1,1- dioxy [3-Phenylisothiazolidine 1,1-dioxide]
White solid
1H NMR(400MHz,CDCl3)δ7.54–7.31(m,5H),4.76–4.70(m,2H),3.44– 3.29(m,1H),
3.20 (m, J=12.6,10.6,7.6Hz, 1H), 2.80-2.73 (m, 1H), 2.45-2.34 (m, 1H)
Embodiment 4:
3- (4- nitrobenzophenone) isothiazolidine -1,1- dioxy [3- (4-Nitrophenyl) isothiazolidine 1,1-
dioxide]
White solid；Yield 52%；1H NMR(400MHz,CDCl3) δ 8.25 (d, J=8.7Hz, 2H), 7.62 (d, J=
8.7Hz, 2H), 4.85 (m, J=7.9Hz, 1H), 4.74 (br s, 1H), 3.40 (ddd, J=12.3,7.3,2.7Hz, 1H),
3.21 (td, J=12.0,7.6Hz, 1H), 2.88 (ddd, J=13.8,7.1,4.6Hz, 1H), 2.50-2.25 (m, 1H)；13C
NMR(100MHz,CDCl3)δ148.0,147.9,127.0,124.5,57.2, 48.2,32.0；HRMS(ESI+)calc'd
for C9H10ClNNaO2S[M+Na]+:265.0253,found 265.0254.
Embodiment 5:
3- (3- methoxyphenyl) isothiazolidine -1,1- dioxy [3- (3-Methoxyphenyl) isothiazolidine
1,1-dioxide]
White solid；Yield 66%；1H NMR(400MHz,CDCl3) δ 7.30 (t, J=7.9Hz, 1H), 6.97 (d, J=
8.2Hz, 2H), 6.87 (d, J=8.2Hz, 1H), 4.75-4.67 (m, 1H), 4.55 (br s, 1H), 3.82 (s, 3H), 3.44-
3.29(m,1H),3.24–3.16(m,1H),2.81–2.73(m,1H),2.45–2.37 (m,1H)；13C NMR(100MHz,
CDCl3)δ160.2,141.9,130.3,118.2,114.0,111.6,58.2, 55.5,48.2,32.2；HRMS(ESI+)
calc’d for C10H13NNaO3S[M+Na]+:250.0508,found 250.0513.
Embodiment 6:
3- (3- bromophenyl) isothiazolidine -1,1- dioxy [3- (3-Bromophenyl) isothiazolidine 1,1-
dioxide]
White solid；Yield 74%；1H NMR(400MHz,CDCl3) δ 7.56 (s, 1H), 7.46 (dd, J=7.9,
1.0Hz, 1H), 7.35 (d, J=7.8Hz, 1H), 7.30-7.21 (m, 1H), 4.73-4.65 (m, 2H), 3.43-3.31 (m,
1H), 3.19 (m, J=12.5,11.0,7.6Hz, 1H), 2.79 (m, J=10.4,7.3,3.4 Hz, 1H), 2.49-2.28 (m,
1H)；13C NMR(100MHz,CDCl3)δ142.7,131.7,130.8, 129.2,124.8,123.2,57.5,48.2,32.1；
HRMS(ESI+)calc’d for C9H10BrNNaO2S [M+Na]+:297.9508,found 297.9509.
Embodiment 7:
3- (2- methoxyphenyl) isothiazolidine -1,1- dioxy [3- (2-Methoxyphenyl) isothiazolidine
1,1-dioxide]
White solid；Yield 77%；1H NMR(400MHz,CDCl3) δ 7.45 (dd, J=7.6,1.5Hz, 1H), 7.34-
7.28 (m, 1H), 7.00-6.97 (m, 1H), 6.90 (d, J=8.2Hz, 1H), 4.96 (dd, J=8.3,7.0Hz, 1H), 3.86
(s,3H),3.34–3.27(m,1H),3.24–3.16(m,1H),2.84–2.76(m, 1H),2.45–2.35(m,1H)；13C
NMR(100MHz,CDCl3)δ156.6,129.5,127.5,127.3, 121.2,110.7,55.5,54.4,48.2,30.4；
HRMS(ESI+)calc’d for C10H13NNaO3S [M+Na]+:250.0508,found 250.0505.
Embodiment 8:
3- (2- bromophenyl) isothiazolidine -1,1- dioxy [3- (2-Bromophenyl) isothiazolidine 1,1-
dioxide 2h])
White solid；Yield 61%；1H NMR(400MHz,CDCl3) δ 7.73 (dd, J=7.8,1.6Hz, 1H), 7.54
(dd, J=8.0,1.1Hz, 1H), 7.42-7.34 (m, 1H), 7.18 (td, J=7.7,1.7Hz, 1H), 5.16 (dd, J=
14.8,6.7Hz, 1H), 4.70 (br s, 1H), 3.33 (ddd, J=12.1,7.1,3.7Hz, 1H), 3.23-3.12 (m, 1H),
3.06–2.98(m,1H),2.30–2.20(m,1H)；13C NMR(100MHz, CDCl3)δ139.7,133.1,129.8,
128.5,127.6,121.8,57.2,48.0,30.1；HRMS(ESI+) calc'd for C9H10BrNNaO2S[M+Na]+:
297.9508,found 297.9505.
Embodiment 9:
3- (4- chlorphenyl) isothiazolidine -1,1- dioxy [3- (4-Chlorophenyl) isothiazolidine 1,1-
dioxide]
White solid；Yield 80%；1H NMR(400MHz,CDCl3) δ 7.34-7.32 (m, 4H), 4.71 (t, J=
6.6Hz,1H),4.66(br s,1H),3.36–3.30(m,1H),3.22–3.14(m,1H),2.79– 2.71(m,1H),
2.38–2.27(m,1H)；13C NMR(100MHz,CDCl3)δ138.9,134.4,129.3, 127.5,57.6,48.3,32.3；
HRMS(ESI+)calc’d for C9H10ClNNaO2S[M+Na]+: 254.0013,found 254.0013.
Embodiment 10:
3- (4- bromophenyl) isothiazolidine -1,1- dioxy [3- (4-Bromophenyl) isothiazolidine 1,1-
dioxide]
White solid；Yield 75%；1H NMR(400MHz,CDCl3) δ 7.50 (d, J=8.3Hz, 2H), 7.29 (d, J=
8.4Hz, 2H), 4.87-4.59 (m, 2H), 3.35 (ddd, J=10.9,7.6,3.1Hz, 1H), 3.26-3.13 (m, 1H),
2.85–2.70(m,1H),2.44–2.25(m,1H)；13C NMR(100MHz, CDCl3)δ139.5,132.3,127.9,
122.4,57.6,48.3,32.2；HRMS(ESI+)calc'd for C9H10BrNNaO2S[M+Na]+:297.9508,found
297.9512.
Embodiment 11:
3- (4- trifluoromethyl) isothiazolidine -1,1- dioxy [3- (4- (Trifluoromethyl) phenyl)
isothiazolidine 1,1-dioxide]
White solid；Yield 88%；1H NMR(400MHz,CDCl3) δ 7.64 (d, J=8.2Hz, 2H), 7.54 (d, J=
8.2Hz, 2H), 4.87-4.79 (m, 2H), 3.37 (ddd, J=12.3,7.5,3.2Hz, 1H), 3.27-3.14 (m, 1H),
2.84–2.80(m,1H),2.47–2.26(m,1H)；13C NMR(100MHz, CDCl3) δ 144.6 (q, J=1.0Hz), 130.8
(q, J=32.4Hz), 126.5,126.1 (q, J=3.8Hz), 124.0 (q, J=270.5Hz), 57.6,48.2,32.1；19F
NMR(376MHz,CDCl3)δ–62.61(s)； HRMS(ESI+)calc'd for C10H10F3NNaO2S[M+Na]+:
288.0277,found 288.0282.
Embodiment 12:
3- (3- aminomethyl phenyl) isothiazolidine -1,1- dioxy [3- (3-Tolyl) isothiazolidine 1,1-
dioxide]
White solid；Yield 89%；1H NMR(400MHz,CDCl3)δ7.30–7.25(m,1H),7.24 –7.12(m,
3H),4.72–4.68(m,1H),4.51(br s,1H),3.39–3.33(m,1H),3.25–3.17 (m,1H),2.78–2.73
(m,1H),2.46–2.38(m,1H),2.37(s,3H).
Embodiment 13:
3- (2- aminomethyl phenyl) isothiazolidine -1,1- dioxy [3- (2-Tolyl) isothiazolidine 1,1-
dioxide]
White solid；Yield 81%；1H NMR(400MHz,CDCl3) δ 7.58 (d, J=7.4Hz, 1H), 7.30-7.23
(m, 1H), 7.21 (dd, J=7.2,1.2Hz, 1H), 7.17 (d, J=7.2Hz, 1H), 4.97 (t, J=6.8Hz, 1H), 4.51
(br s, 1H), 3.35 (ddd, J=12.3,7.8,4.3Hz, 1H), 3.21 (ddd, J=12.6,9.8,7.6Hz, 1H), 2.78
(ddd, J=11.6,10.2,5.8Hz, 1H), 2.37 (s, 3H), 2.37-2.28 (m, 1H)
Embodiment 14:
3- phenyl -1,2- thiazan -1,1- dioxy [3-phenyl-1,2-thiazinane 1,1-dioxide]
White solid；Yield 70%；1H NMR(400MHz,CDCl3) δ 7.43-7.29 (m, 5H), 4.59 (dd, J=
11.9,3.4Hz, 1H), 4.24 (br s, 1H), 3.33-3.19 (m, 1H), 3.01 (td, J=13.1,5.2 Hz, 1H), 2.43-
2.23 (m, 2H), 2.06 (ddd, J=13.9,5.9,3.0Hz, 1H), 1.73 (ddd, J=17.1,13.0,8.5Hz, 1H)
Embodiment 15:
3- methyl -2,3- dihydrobenzo isothiazolidine -1,1- dioxy [3-methyl-2,3-dihydrobenzo [d]
isothiazole 1,1-dioxide]
White solid；Yield 70%；1H NMR(400MHz,CDCl3) δ 7.78 (d, J=7.7Hz, 1H), 7.64 (t, J=
7.5Hz, 1H), 7.54 (t, J=7.4Hz, 1H), 7.40 (d, J=7.7Hz, 1H), 4.82-4.78 (m, 1H), 1.63 (d, J=
6.4Hz,3H).
Embodiment 16:
2,3- dihydrobenzo isothiazolidine -1,1- dioxy [2,3-Dihydrobenzo [d] isothiazole 1,1-
dioxide]
White solid；Yield 50%；1H NMR(400MHz,CDCl3) δ 7.80 (d, J=7.8Hz, 1H), 7.62 (td, J
=7.6,1.1Hz, 1H), 7.56-7.51 (m, 1H), 7.40 (d, J=7.7Hz, 1H), 4.81 (br s, 1H), 4.54 (s,
2H).
Embodiment 17:
3- ((trimethyl silicon substrate) acetenyl) isothiazolidine -1,1- dioxy [3- ((trimethylsilyl) ethynyl)
isothiazolidine 1,1-dioxide]
Yellow solid；Yield 53%；1H NMR(400MHz,CDCl3)δ4.59–4.22(m,2H), 3.31–3.20(m,
1H),3.19–3.14(m,1H),2.86–2.66(m,1H),2.61–2.40(m,1H), 0.17(s,9H)；13C NMR
(100MHz,CDCl3)δ102.0,91.2,46.7,46.0,30.9,-0.21； HRMS(ESI+)calc'd for
C8H15NNaO2SSi[M+Na]+:240.0485,found 240.0489.
Embodiment 18:
3,3- dimethyl isothiazolidine -1,1- dioxy [3,3-dimethylisothiazolidine 1,1-dioxide]
White solid；Yield 68%；1H NMR(400MHz,CDCl3) δ 4.06 (br s, 1H), 3.23 (t, J=7.5Hz,
2H), 2.29 (t, J=7.5Hz, 2H), 1.40 (s, 6H)；13C NMR(100MHz,CDCl3)δ 57.9,48.3,37.0,29.7；
HRMS(ESI+)calc’d for C5H11NNaO2S[M+Na]+:172.0403, found 172.0404.
Embodiment 19:
3- methyl-isothiazol alkane -1,1- dioxy [3-methylisothiazolidine 1,1-dioxide]
White solid；Yield 74%；
1H NMR(400MHz,CDCl3)δ4.04(br s,1H),3.76–3.68(m,1H),3.26–3.20 (m,1H),
3.17-3.09 (m, 1H), 2.55-2.48 (m, 1H), 2.09-1.99 (m, 1H), 1.33 (d, J=6.3Hz, 3H)
Embodiment 20:
Method one: ferrous perchlorate (5.1mg, 0.02mmol) and L1 (8.1mg, 0.04mmol) are first weighed and is reacted in 4mL
In bottle, 1.0mL acetonitrile is added and is dissolved, stirs 30 minutes, after complexes ira situ, weighs at room temperatureMolecular sieve
(50.0mg), dimethyl malonic acid iodobenzene (167.0mg, 0.5mmol) and corresponding sulfonamide substrate (38.6mg,
0.2mmol), it is added in reaction system, adds the dissolution of 1.0mL acetonitrile, at 80 DEG C, react 2h, filtering, filter cake is used appropriate full
It is washed with sodium bicarbonate, water phase is extracted with dichloromethane 3 times (3 × 10mL), merges organic phase, and saturated salt solution cleaning is anhydrous
Sodium sulphate is dried, and after removing solvent, column chromatography for separation (methylene chloride/petroleum ether=1:1~methylene chloride) is obtained in five yuan
Sulfonamide 3- amyl isothiazolidine -1,1- dioxy and hexa-atomic interior sulfonamide 3- butyl isothiazine alkane -1,1- dioxy are the mixed of 3:5
It closes object (32.6mg, 85%).
Method two: first weighing ferrous perchlorate (5.1mg, 0.02mmol) and L6 (10.1mg, 0.06mmol) is anti-in 4mL
It answers in bottle, 1.0mL acetonitrile is added and is dissolved, stirs 30 minutes, after complexes ira situ, weighs at room temperatureMolecular sieve
(50.0mg), dimethyl malonic acid iodobenzene (162.5mg, 0.5mmol) and corresponding sulfonamide substrate (38.6mg,
0.2mmol), it is added in reaction system, adds the dissolution of 1.0mL acetonitrile, at 80 DEG C, react 2h, filtering, filter cake is used appropriate full
It is washed with sodium bicarbonate, water phase is extracted with dichloromethane 3 times (3 × 10mL), merges organic phase, and saturated salt solution cleaning is anhydrous
Sodium sulphate is dried, and after removing solvent, column chromatography for separation (methylene chloride/petroleum ether=1:1~methylene chloride) is obtained in five yuan
Sulfonamide 3- amyl isothiazolidine -1,1- dioxy and hexa-atomic interior sulfonamide 3- butyl isothiazine alkane -1,1- dioxy ratio are 2:1's
Mixture (28.6mg, 75%).
3- amyl isothiazolidine -1,1- dioxy [3-Pentylisothiazolidine 1,1-dioxide]
Colourless liquid；1H NMR(400MHz,CDCl3)δ4.31(br s,1H),3.61–3.53(m,1H), 3.26–3.15
(m,1H),3.13–3.06(m,1H),2.59–2.43(m,1H),2.12–1.97(m,1H), 1.64–1.53(m,2H),1.42–
1.15 (m, 6H), 0.89 (t, J=6.8Hz, 3H)；13C NMR(100 MHz,CDCl3)δ55.4,48.2,36.1,31.6,
30.0,25.9,22.6,14.1；HRMS(ESI+)calc'd for C8H17NNaO2S[M+Na]+:214.0872,found
214.0873.
3- butyl isothiazine alkane -1,1- dioxy [3-Butyl-1,2-thiazinane 1,1-dioxide]
Colourless liquid；1H NMR(400MHz,CDCl3)δ3.74(br s,1H),3.50–3.43(m,1H), 3.20(dt,J
=13.3,3.5Hz, 1H), 2.98-2.72 (m, 1H), 2.28-2.12 (m, 2H), 1.84-1.80 (m, 1H), 1.52-1.14
(m, 7H), 0.90 (t, J=7.0Hz, 3H)；13C NMR(100MHz,CDCl3)δ 56.8,49.6,35.6,30.7,27.6,
23.2,22.5,14.1.
Embodiment 21:
3- phenyl -1,2- thiophene azete alkane -1,1- dioxy [3-Phenyl-1,2-thiazetidine 1,1-dioxide]
MS=183.04
Embodiment 22:
[Tetrahydro-1H,3H-isothiazolo[4,3-c]isothiazole 2,2,5,5-tetraoxide]
MS=211.99
Embodiment 23:
Isothiazolidine -1,1- dioxy [isothiazolidine 1,1-dioxide]
MS=121.02
Embodiment 24:
3- methyl -6- phenyl -1,2- isothiazine alkane -1,1- dioxy [3-methyl-6-phenyl-1,2-thiazinane
1,1-dioxide]
MS=225.08
Embodiment 25:
1,2- isothiazine alkane -1,1- dioxy [1,2-thiazinane 1,1-dioxide]
MS=135.04
Embodiment 26:
Methyl -3,4, -2 hydrogenated naphthalene of 6,7,8,9- hexahydro [2,3-e] and isothiazine alkane -3- carboxyl -1,1- dioxy
[methyl 3,4,6,7,8,9-hexahydro-2H-naphtho[2,3-e][1,2]thiazine-3-carboxylate 1,
1-dioxide]
MS=295.09
Embodiment 27:
(E) -5- (3,5- di-t-butyl -4- hydroxy-benzylidene isothiazine alkane -1,1- dioxy [(E) -5- (3,5-di-
tert-butyl-4-hydroxybenzylidene)isothiazolidine 1,1-dioxide]
MS=337.17
Embodiment 28:
- 3 carbonyl -1,1- dioxy [methyl isothiazolidine-3-carboxylate 1,1- of methyl-isothiazol alkane
dioxide]
MS=179.03
Embodiment 29-42:
Ferrous perchlorate (5.2mg, 0.02mmol) and ligand L 2 (8.0mg, 0.04mmol) are first weighed in 4mL reaction flask
In, 1.0mL acetonitrile is added and is dissolved, stirs 30 minutes, after complexes ira situ, weighs at room temperatureMolecular sieve
(50.0mg), pivalic acid iodobenzene (163.8mg, 0.4mmol) and corresponding sulfonamide H (0.2mmol) are added in reaction system, then
1.0mL acetonitrile is added, after TLC monitoring fully reacting is reacted at 80 DEG C, trifluoroacetic acid iodobenzene is added into reaction system
(103.1mg, 0.24mmol) reacts 1h again at 80 DEG C, then filters, and filter cake is washed with appropriate saturated sodium bicarbonate, water phase
It is extracted with dichloromethane 3 times (3 × 10mL), merges organic phase and is cleaned with saturated salt solution, anhydrous sodium sulfate is dried, and is taken off
After solvent, column chromatography for separation (methylene chloride/petroleum ether=1:1~methylene chloride) obtains interior sulfonyl imide compounds G.
Embodiment 29:
3- phenyl -4,5- dihydro isothiazole -1,1- dioxy [3-phenyl-4,5-dihydroisothiazole 1,1-
dioxide]
White solid；Yield 88%；1H NMR(400MHz,CDCl3) δ 8.03 (dd, J=8.4,1.2Hz, 2H), 7.74-
7.61 (m, 1H), 7.53 (t, J=7.7Hz, 2H), 3.75-3.61 (m, 2H), 3.56-3.35 (m, 2H)
Embodiment 30:
3- (4- aminomethyl phenyl) -4,5- dihydro isothiazole -1,1- dioxy [3- (4-Tolyl) -4,5-
dihydroisothiazole 1,1-dioxide]
White solid；1H NMR(400MHz,CDCl3) δ 7.92 (d, J=8.3Hz, 2H), 7.32 (d, J=8.3Hz,
2H), 3.65 (dd, J=8.2,6.4Hz, 2H), 3.43 (dd, J=8.1,6.5Hz, 2H), 2.45 (s, 3H)
Embodiment 31:
3- (4- nitrobenzophenone) -4,5- dihydro isothiazole -1,1- dioxy [3- (4-Nitrophenyl) -4,5-
dihydroisothiazole 1,1-dioxide]
White solid；Yield 75%；1H NMR(400MHz,CD3CN)δ8.42–8.28(m,2H), 8.28–8.15(m,
2H), 3.76 (dd, J=8.0,6.3Hz, 2H), 3.47 (dd, J=7.9,6.3Hz, 2H)；13C NMR(100MHz,CD3CN)δ
177.2,151.9,137.5,131.1,124.9,45.4,35.1；HRMS (ESI+)calc'd for C9H8N2NaO4S[M+
Na]+:263.0097,found 263.0093.
Embodiment 32:
3- (3- methoxyphenyl) -4,5- dihydro isothiazole -1,1- dioxy [3- (3-Methoxyphenyl) -4,5-
dihydroisothiazole 1,1-dioxide]
White solid；Yield 81%；1H NMR(400MHz,CDCl3) δ 7.63-7.58 (m, 1H), 7.52 (d, J=
7.7Hz, 1H), 7.42 (t, J=8.0Hz, 1H), 7.19 (dd, J=8.2,2.4Hz, 1H), 3.87 (s, 3H), 3.75-3.55
(m,2H),3.56–3.31(m,2H)；13C NMR(100MHz,CDCl3)δ176.0, 160.1,132.2,130.2,121.6,
121.4,113.3,55.7,44.4,33.7；HRMS(ESI+)calc'd for C10H11NNaO3S[M+Na]+:248.0352,
found 248.0352.
Embodiment 33:
3- (3- bromophenyl) -4,5- dihydro isothiazole -1,1- dioxy [3- (3-Bromophenyl) -4,5-
dihydroisothiazole 1,1-dioxide]
White solid；Yield 78%；1H NMR(400MHz,CDCl3)δ8.16(s,1H),8.05–7.90(m, 1H),
7.80-7.77 (m, 1H), 7.44-7.40 (m, 1H), 3.64 (dd, J=8.3,6.2Hz, 2H), 3.46 (dd, J=8.1,
6.3Hz,2H)；13C NMR(100MHz,CDCl3)δ174.6,137.5,132.9,132.1,130.8, 127.7,123.5,
44.4,33.6；HRMS(ESI+)calc'd for C9H8BrNNaO2S[M+Na]+: 295.9351,found 295.9347.
Embodiment 34:
3- (2- methoxyphenyl) -4,5- dihydro isothiazole -1,1- dioxy [3- (2-Methoxyphenyl) -4,5-
dihydroisothiazole 1,1-dioxide]
White solid；1H NMR(400MHz,CDCl3) δ 8.15 (dd, J=7.9,1.8Hz, 1H), 7.66-7.48 (m,
1H), 7.09-7.04 (m, 1H), 7.01 (d, J=8.5Hz, 1H), 3.93 (s, 3H), 3.82 (t, J=7.2Hz, 2H), 3.35
(t, J=6.8Hz 2H)；13C NMR(100MHz,CDCl3)δ178.0,160.5, 135.8,132.5,121.4,120.1,
112.0,55.8,44.2,37.9；HRMS(ESI+)calc'd for C10H11NNaO3S[M+Na]+:248.0352,found
248.0352.
Embodiment 35:
3- (2- bromophenyl) -4,5- dihydro isothiazole -1,1- dioxy [3- (2-Bromophenyl) -4,5-
dihydroisothiazole 1,1-dioxide]
White solid；1H NMR(400MHz,CDCl3) δ 7.71 (dd, J=7.8,1.3Hz, 1H), 7.66 (dd, J=
7.6,1.9Hz, 1H), 7.46 (dd, J=7.5,1.4Hz, 1H), 7.43-7.38 (m, 1H), 3.94-3.68 (t, 2H), 3.45
(t,2H)；13C NMR(100MHz,CDCl3)δ178.9,134.6,133.6,133.3, 131.0,128.0,121.2,44.7,
37.4；HRMS(ESI+)calc'd for C9H8BrNNaO2S[M+Na]+: 295.9351,found 295.9350.
Embodiment 36:
3- (4- chlorphenyl) -4,5- dihydro isothiazole -1,1- dioxy [3- (4-Chlorophenyl) -4,5-
dihydroisothiazole 1,1-dioxide]
White solid；Yield 85%；1H NMR(400MHz,CDCl3) δ 7.96 (d, J=8.6Hz, 2H), 7.51 (d, J=
8.5Hz,2H),3.82–3.57(t,2H),3.56–3.36(t,2H)；13C NMR(100MHz, CDCl3)δ174.8,141.4,
130.5,129.8,129.4,44.5,33.6；HRMS(ESI+)calc'd for C9H8ClNNaO2S[M+Na]+:251.9856,
found 251.9860.
Embodiment 37:
3- (4- bromophenyl) -4,5- dihydro isothiazole -1,1- dioxy [3- (4-Bromophenyl) -4,5-
dihydroisothiazole 1,1-dioxide]
White solid；1H NMR(400MHz,CDCl3) δ 7.88 (d, J=8.6Hz, 2H), 7.68 (d, J=8.6Hz, 2H),
3.67–3.60(t,2H),3.50–3.41(t,2H)；13C NMR(100MHz,CDCl3)δ 174.9,132.8,130.5,
130.1,129.9,44.4,33.6；HRMS(ESI+)calc'd for C9H8BrNNaO2S[M+Na]+:295.9351,found
295.9353.
Embodiment 38:
3- (4- trifluoromethyl) -4,5- dihydro isothiazole -1,1- dioxy [3- (4- (Trifluoromethyl)
phenyl)-4,5-dihydroisothiazole 1,1-dioxide]
White solid；Yield 92%；1H NMR(400MHz,CD3CN) δ 8.21 (d, J=8.2Hz, 2H), 7.87 (d, J=
8.3Hz, 2H), 3.75 (t, J=7.9,6.3Hz, 2H), 3.53-3.32 (t, 2H)；13C NMR (100MHz,CD3CN)δ
177.7,135.9 (q, J=1.0Hz), 135.1 (q, J=32.5Hz), 130.6,126.9 (q, J=3.8Hz), 124.7 (q, J
=270.2Hz), 45.3,34.9；19F NMR(376MHz, CD3CN)δ–63.77(s)；HRMS(ESI+)calc'd for
C10H8F3NNaO2S[M+Na]+:286.0120, found 286.0118.
Embodiment 39:
3- (4- methoxyphenyl) -4,5- dihydro isothiazole -1,1- dioxy [3- (4-Methoxyphenyl) -4,5-
dihydroisothiazole 1,1-dioxide]
White solid；Yield 78%；1H NMR(400MHz,CDCl3) δ 7.99 (d, J=8.9Hz, 2H), 7.00 (d, J=
8.9Hz,2H),3.90(s,3H),3.74–3.58(t,2H),3.49–3.35(t,2H)；13C NMR(100MHz,CDCl3)δ
175.0,164.9,131.6,123.5,114.7,55.8,44.5,33.4；HRMS (ESI+)calc'd for C10H11NNaO3S
[M+Na]+:248.0352,found 248.0356.
Embodiment 40:
3- methyl -4,5- dihydro isothiazole -1,1- dioxy [3-Methyl-4,5-dihydroisothiazole 1,1-
dioxide]
White solid；1H NMR(400MHz,CDCl3)δ3.31–3.24(t,2H),3.23–3.16(t,2H), 2.34(s,
3H).
Embodiment 41:
Methyl -4,5- dihydro isothiazole -3- carbonyl -1,1- dioxy [methyl 4,5-dihydroisothiazole-3-
carboxylate 1,1-dioxide]
MS=177.01
Embodiment 42:
(E) -3- (1- allyl) -4,5-4,5- dihydro isothiazole -1,1- dioxy [(E) -3- (prop-1-en-1-yl) -
4,5-dihydroisothiazole 1,1-dioxide]
MS=159.04.
Claims (8)
1. a kind of interior sulfamide compound, it is characterised in that: including interior sulfamide compound E and interior sulfamide compound
G；
The molecular structural formula of the interior sulfamide compound E is as follows:
The molecular structural formula of the interior sulfamide compound G is as follows:
Wherein R1、R2、R3、R4、R5It is independently；N, which appoints, is derived from 0,1 or 2；
The R1Optionally from hydrogen, alkyl, alkenyl, aryl, substituted aryl, alkoxy, phenol oxygroup, alkylthio group, phenol sulfenyl, alkyl
Amido or arylamino；
The R2Optionally from hydrogen, alkyl, alkenyl, aryl, substituted aryl, alkoxy, phenol oxygroup, alkylthio group, phenol sulfenyl, alkyl
Amido or arylamino；
The R3Optionally from hydrogen, alkyl, alkenyl, aryl；
The R4Optionally from hydrogen, alkyl, alkenyl, aryl；
The R5Optionally from hydrogen, alkyl, alkenyl, aryl, substituted aryl, alkoxy, phenol oxygroup, alkylthio group, phenol sulfenyl, alkyl
Amido or arylamino.
2. a kind of preparation method of sulfamide compound interior as described in claim 1, it is characterised in that: the following steps are included:
Iron complex catalyst C, stock sulfonamide B, oxidant D are added in organic solvent and are stirred to react, through excessive after reaction
From purification, interior sulfamide compound E is obtained；In raw material dosage, iron complex catalyst C, stock sulfonamide B, oxidant D
The mass ratio of the material range is 0.01:1:1 to 0.5:1:5；
Obtained interior sulfamide compound E is using sulfonamide B as raw material, and reaction equation is as follows:
Alternatively, iron complex catalyst C, stock sulfonamide H, oxidant D are added in organic solvent and are stirred to react, detection reaction
After the completion, after adding oxidant F reaction, into isolating and purifying, interior sulfonyl imide compounds G is obtained；In raw material dosage, institute
State iron complex catalyst C, stock sulfonamide H, oxidant D, oxidant F the mass ratio of the material range be 0.01:1:1:1 to 0.5:
1:5:2；
Obtained interior sulfamide compound G is using sulfonamide H as raw material, and reaction equation is as follows:
Wherein R1、R2、R3、R4、R5It is independently；N, which appoints, is derived from 0,1 or 2；
The R1Optionally from hydrogen, alkyl, alkenyl, aryl, substituted aryl, alkoxy, phenol oxygroup, alkylthio group, phenol sulfenyl, alkyl
Amido or arylamino；
The R2Optionally from hydrogen, alkyl, alkenyl, aryl, substituted aryl, alkoxy, phenol oxygroup, alkylthio group, phenol sulfenyl, alkyl
Amido or arylamino；
The R3Optionally from hydrogen, alkyl, alkenyl, aryl；
The R4Optionally from hydrogen, alkyl, alkenyl, aryl；
The R5Optionally from hydrogen, alkyl, alkenyl, aryl, substituted aryl, alkoxy, phenol oxygroup, alkylthio group, phenol sulfenyl, alkyl
Amido or arylamino.
The structure of the oxidant F is Ar2I(OCOCF3)2, wherein Ar2Appoint and is derived from phenyl, substituted phenyl, naphthalene, substituted naphthalene
Base；
The iron complex catalyst C is the complex compound that molysite and ligand are formed；Wherein molysite is optionally from trivalent iron salt or two
Valence molysite, structural formula are Fe (X)2Or Fe (X)3；X is optionally from following anion: Cl–、Br–、I–、AcO–、TfO–、ClO4 –、BF4 –
Or SbF6 –；Wherein ligand is appointed and is derived from such as flowering structure:Wherein
R6Appoint and is derived from hydrogen, the alkyl of C1-C6, phenyl or substituted phenyl；Wherein R7、R8、R9Independent substituent group respectively, it is identical or
Person is different；R7、R8、R9Appoint and is derived from hydrogen, the alkyl of C1-C6 or containing fluoroalkyl, aryl, heteroaryl, alkoxy, alkyl amine group, virtue
Base amino；Wherein the ratio of the amount of the substance of iron and ligand is 1:1 to 1:3；
The oxidant D is high price iodide, appoints and is derived from oxygen iodobenzene or Ar1I(OCOR)2；Wherein Ar1Appoint be derived from phenyl, replace
Phenyl, naphthalene or substituted naphthalene；Wherein R appoints the alkyl for being derived from C1-C6 or containing fluoroalkyl.
3. the preparation method of sulfamide compound in as claimed in claim 2, it is characterised in that: the object of the iron and ligand
The ratio of the amount of matter is 1:2.
4. the preparation method of sulfamide compound in as claimed in claim 2 or claim 3, it is characterised in that: described to contain fluoroalkyl
It is any in iodobenzene acetate, trifluoroacetic acid iodobenzene, pivalic acid iodobenzene, dimethyl malonic acid iodobenzene or benzoic acid iodobenzene.
5. the preparation method of sulfamide compound in as claimed in claim 2 or claim 3, it is characterised in that: described to be stirred to react
Temperature be 20 degrees Celsius to 120 degrees Celsius；The separating-purifying is any in column chromatography, recrystallization or distillation.
6. such as the preparation method of claim 4 or the interior sulfamide compound, it is characterised in that: described to be stirred to react
Temperature is 20 degrees Celsius to 120 degrees Celsius；The separating-purifying is any in column chromatography, recrystallization or distillation.
7. the preparation method of sulfamide compound in as claimed in claim 2 or claim 3, it is characterised in that: described is organic molten
Agent is optionally from the combination of following solvent or solvent: acetonitrile, the tert-butyl alcohol, 1,2- dichloroethanes, methylene chloride, tetrahydrofuran, first
Base tertbutyl ether, dioxane, dimethyl sulfoxide, N, N '-dimethyl formamide, trifluoroethanol, benzene,toluene,xylene or chlorine
Benzene.
8. the preparation method of sulfamide compound in as claimed in claim 7, it is characterised in that: the organic solvent is second
Nitrile or 1,2- dichloroethanes.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
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| CN1735592A (en) * | 2002-12-05 | 2006-02-15 | 葛兰素集团有限公司 | Hydroxyethylamine derivatives for the treatment of alzheimer's disease |
| CN104854093A (en) * | 2012-12-03 | 2015-08-19 | 辉瑞大药厂 | Novel selective androgen receptor modulators |
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| CN1735592A (en) * | 2002-12-05 | 2006-02-15 | 葛兰素集团有限公司 | Hydroxyethylamine derivatives for the treatment of alzheimer's disease |
| CN104854093A (en) * | 2012-12-03 | 2015-08-19 | 辉瑞大药厂 | Novel selective androgen receptor modulators |
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| CORINNE FRUIT ET AL.: "Intramolecular Asymmetric Amidations of Sulfonamides and Sulfamates Catalyzed by Chiral Dirhodium(II) Complexes", 《HELVETICA CHIMICA ACTA》 * |
| DAYOU ZHONG ET AL.: "Synthesis of Sultams and Cyclic N‑Sulfonyl Ketimines via Iron-Catalyzed Intramolecular Aliphatic C−H Amidation", 《ORGANIC LETTERS》 * |
| HELENE WOLLEB ET AL.: "Synthesis and Structure−Activity Relationship Studies of Anti-Inflammatory Epoxyisoprostane Analogues", 《ORGANIC LETTERS》 * |
| YUNGEN LIU ET AL.: "Nonheme Iron-Mediated Amination of C(sp3)-H Bonds. Quinquepyridine-Supported Iron-Imide/Nitrene Intermediates by Experimental Studies and DFT Calculations", 《JOURNAL OF THE AMERICAN CHEMICAL SOCIETY》 * |
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