CN110372628B - 内磺酰胺类化合物及其制备方法 - Google Patents
内磺酰胺类化合物及其制备方法 Download PDFInfo
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- CN110372628B CN110372628B CN201910616230.3A CN201910616230A CN110372628B CN 110372628 B CN110372628 B CN 110372628B CN 201910616230 A CN201910616230 A CN 201910616230A CN 110372628 B CN110372628 B CN 110372628B
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- 150000003456 sulfonamides Chemical class 0.000 claims description 23
- 239000001257 hydrogen Substances 0.000 claims description 19
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- 125000001072 heteroaryl group Chemical group 0.000 claims description 2
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 claims description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Chemical compound [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 claims description 2
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- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 22
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- XGYCWCIGCYGQFU-UHFFFAOYSA-N 1,2-thiazolidine 1,1-dioxide Chemical compound O=S1(=O)CCCN1 XGYCWCIGCYGQFU-UHFFFAOYSA-N 0.000 description 15
- 239000002808 molecular sieve Substances 0.000 description 11
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- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 8
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- 238000011065 in-situ storage Methods 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
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- 239000008346 aqueous phase Substances 0.000 description 4
- 238000010668 complexation reaction Methods 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
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- 230000002194 synthesizing effect Effects 0.000 description 3
- DLBPTOMGZXBZOX-UHFFFAOYSA-N 1,2-thiazole 1,1-dioxide Chemical compound O=S1(=O)C=CC=N1 DLBPTOMGZXBZOX-UHFFFAOYSA-N 0.000 description 2
- 238000004293 19F NMR spectroscopy Methods 0.000 description 2
- 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 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
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- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000532 dioxanyl group Chemical group 0.000 description 1
- 125000003709 fluoroalkyl group Chemical group 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
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- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 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
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- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- UETBQZUGBOZWRA-UHFFFAOYSA-N methyl 1,1-dioxo-1,2-thiazolidine-3-carboxylate Chemical compound COC(=O)C1CCS(=O)(=O)N1 UETBQZUGBOZWRA-UHFFFAOYSA-N 0.000 description 1
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- 229910052757 nitrogen Inorganic materials 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
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- 238000007154 radical cyclization reaction Methods 0.000 description 1
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 238000006257 total synthesis reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Images
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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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明提供了一种内磺酰胺类化合物及其制备方法。本发明的具体方法是把催化剂C，磺酰胺B，氧化剂D加入有机溶剂中反应，经过分离提纯，得到一种内磺酰胺类化合物E，或者待检测反应完成后，再加入氧化剂F反应后，进分离纯化，得到内磺酰亚胺类化合物G。该方法所需的催化剂是廉价易得，毒性低的铁络合物。当使用磺酰胺H时，通过按照以上方法反应完毕后，再额外加入另一个氧化剂F的条件下，实现一锅法合成内磺酰亚胺类化合物。所制备的内磺酰胺和内磺酰亚胺类化合物广泛地应用于药物化学、材料化学和有机合成领域。
Description
技术领域
本发明涉及有机合成技术领域，具体涉及一种内磺酰胺类化合物及其制备方法。
背景技术
磺酰胺结构骨架在一些具有广谱抗菌活性的药物大分子中广泛存在，是一类非常重要的结构片段，在新药合成中发挥着重要作用。特别指出的是，内磺酰胺类结构具有良好的水溶性和稳定性，被视为内酰胺骨架等价物，并广泛应用于药物的结构修饰(如图3所示)，因此在药物化学领域中受到科学家们的广泛关注[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.]，此外，这类结构也可以应用于某些杂环化合物及天然产物全合成[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.]。目前合成这类结构的方法主要包括(1)Diels–Alder环化反应[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)关环烯烃复分解(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)自由基环化[Ueda,M.；Miyabe,H.；Nishimura,A.；Miyata,O.； Takemoto,Y.；Naito,T.Org.Lett.2003,5,3835–3838.]；(4)分子内Heck反应[a) Khalifa,A.；Conway,L.；Geoghegan,K.；Evans,P.TetrahedronLett.2017,58, 4559–4562.b)Laha,J.K.；Sharma,S.；Kirar,S.；Banerjee,U.C.J.Org.Chem.2017, 82,9350–9359.]等。
目前，催化的内磺酰胺骨架的合成方法鲜有报道，而且仅限于苯磺酰叠氮底物分子内胺化，合成苯并磺酰胺结构骨架。近些年来随着酶催化反应的快速发展， Arnold,Fasan和Hartwig课题组相继报道了芳基磺酰叠氮底物在酶催化下，发生分子内胺化，得到了刚性的苯并内磺酰胺结构，具有良好的化学选择性和对映选择性的[a)McIntosh,J.A.；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.]。金属催化剂卟啉钴和铱亚胺复合物也能催化芳基磺酰胺的分子内反应，合成苯并内磺酰胺[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.]。总之，这些方法存在催化剂结构复杂，不易获得，且价格昂贵等缺点，更重要的是，这些方法的反应底物都局限于芳基磺酰叠氮底物，只能用于合成刚性的苯并内磺酰胺产物。
发明内容
为了解决现有技术存在的缺陷，本发明的目的是提供一种内磺酰胺类化合物及其制备方法，即用铁络合物催化的新方法来合成内磺酰胺及内磺酰亚胺类化合物。
为实现上述目的，本发明一方面提供的内磺酰胺类化合物，其特征在于：包括内磺酰胺类化合物E和内磺酰胺类化合物G；
所述内磺酰胺类化合物E的分子结构式如下：
所述内磺酰胺类化合物G的分子结构式如下：
其中R1、R2、R3、R4、R5是分别独立的；n任取自0、1或2；
所述R1任选自氢、烷基、烯基、芳基、取代的芳基、烷氧基、酚氧基、烷硫基、酚硫基、烷基胺基或芳基氨基；
所述R2任选自氢、烷基、烯基、芳基、取代的芳基、烷氧基、酚氧基、烷硫基、酚硫基、烷基胺基或芳基氨基；
所述R3任选自氢、烷基、烯基、芳基；
所述R4任选自氢、烷基、烯基、芳基；
所述R5任选自氢、烷基、烯基、芳基、取代的芳基、烷氧基、酚氧基、烷硫基、酚硫基、烷基胺基或芳基氨基。
本发明另一方面提供的内磺酰胺类化合物的制备方法，其特征在于：包括以下步骤：
将铁络合催化剂C、原料磺酰胺B、氧化剂D加入到有机溶剂中搅拌反应，反应后经过分离提纯，得到内磺酰胺类化合物E；在原料用量上，铁络合催化剂 C、原料磺酰胺B、氧化剂D的物质的量比范围为0.01:1:1至0.5:1:5；
所制得的内磺酰胺类化合物E是以磺酰胺B为原料，反应方程式如下：
或者，将铁络合催化剂C、原料磺酰胺H、氧化剂D加入到有机溶剂中搅拌反应，检测反应完成后，再加入氧化剂F反应后，进分离纯化，得到内磺酰亚胺类化合物G；在原料用量上，所述铁络合催化剂C、原料磺酰胺H、氧化剂D、氧化剂F的物质的量比范围为0.01:1:1:1至0.5:1:5:2；
所制得的内磺酰胺类化合物G是以磺酰胺H为原料，反应方程式如下：
其中R1、R2、R3、R4、R5是分别独立的；n任取自0、1或2；
所述R1任选自氢、烷基、烯基、芳基、取代的芳基、烷氧基、酚氧基、烷硫基、酚硫基、烷基胺基或芳基氨基；
所述R2任选自氢、烷基、烯基、芳基、取代的芳基、烷氧基、酚氧基、烷硫基、酚硫基、烷基胺基或芳基氨基；
所述R3任选自氢、烷基、烯基、芳基；
所述R4任选自氢、烷基、烯基、芳基；
所述R5任选自氢、烷基、烯基、芳基、取代的芳基、烷氧基、酚氧基、烷硫基、酚硫基、烷基胺基或芳基氨基。
所述氧化剂F的结构是Ar2I(OCOCF3)2,其中Ar2任取自苯基、取代的苯基、萘基、取代的萘基；
所述铁络合物催化剂C是铁盐和配体形成的络合物；其中铁盐任选自三价铁盐或者二价铁盐，结构式为Fe(X)2或者Fe(X)3；X任选自如***离子：Cl–、Br–、 I–、AcO–、TfO–、ClO4 –、BF4 –或SbF6 –；其中配体任取自如下结构：
其中R6任取自氢、C1-C6的烷基、苯基或取代的苯基；其中R7、R8、R9分别是独立的取代基，相同或者不同；R7、R8、R9任取自氢、C1-C6的烷基或者含氟烷基、芳基、杂芳基、烷氧基、烷基胺基、芳基氨基；其中铁和配体的物质的量的比例为1:1 至1:3；
所述氧化剂D是高价碘化物，任取自氧碘苯或Ar1I(OCOR)2；其中Ar1任取自苯基、取代的苯基、萘基或取代的萘基；其中R任取自C1-C6的烷基或者含氟烷基。
作为优选方案，所述铁和配体的物质的量的比例为1:2。
进一步地，所述含氟烷基为醋酸碘苯、三氟乙酸碘苯、特戊酸碘苯、二甲基丙二酸碘苯或苯甲酸碘苯中任一种。
更进一步地，所述搅拌反应的温度为20摄氏度至120摄氏度；所述分离提纯为柱层析、重结晶或蒸馏中任一种。
更进一步地，所述的有机溶剂任选自如下溶剂或者溶剂的组合：乙腈、叔丁醇、1,2-二氯乙烷、二氯甲烷、四氢呋喃、甲基叔丁基醚、二氧六环、二甲基亚砜、N、N’-二甲基甲酰胺、三氟乙醇、苯、甲苯、二甲苯或氯苯。
更进一步地，所述有机溶剂为乙腈或1,2-二氯乙烷。
上述反应中，加入分子筛可以提高反应的收率，其中分子筛任选自
分子筛、
分子筛、
分子筛，优选
分子筛；
本发明具有如下优点和有益效果：
(1)本方法首次使用廉价易得的铁催化剂实现了内磺酰胺类化合物的合成，反应操作简单，反应效率高、经济性好；
(2)通过原位加入氧化剂，实现了一锅法制备内磺酰亚胺类化合物，为内磺酰亚胺的合成提供了一种全新的方法；
(3)使用毒性较小的铁催化剂，可以有效减少所合成产物中的重金属残留以及反应本身对环境的污染。
附图说明
图1为本发明内磺酰胺类化合物E反应方程图式；
图2为本发明内磺酰胺类化合物G反应方程图式；
图3为含内磺酰胺骨架的代表性生物活性分子结构。
具体实施方式
通过以下详细说明可以进一步理解本发明的特点和优点。所提供的实施例仅是对本发明方法的说明，而不以任何方式限制本发明揭示的其余内容。
实施例1：以苯丙磺酰胺为标准底物，对铁催化的内磺酰胺合成的反应条件
进行研究：
其中，脚注a为反应在60摄氏度操作；脚注b表示反应没有加入分子筛；其中[Fe]为铁盐；配体结构如表格所画L1-L7所示；mol％指的相对摩尔量，equiv 代表当量，碱代表常用无机碱，solvent指的是有机溶剂，体积为2mL；其中DMF 为N,N’-二甲基甲酰胺，MeCN为乙腈、DCE为1，2-二氯乙烷、1，4-dioxane 为二氧六环、toluene为甲苯。其中，ligand指多齿氮配体，oxidant是氧化剂，yield 指内磺酰胺和内磺酰亚胺的总核磁收率，以均三甲氧基苯为内标物。PhI(OAc)2是醋酸碘苯，PhI(OCOCF3)2是三氟乙酸碘苯，PhI(DMM)是二甲基丙二酸碘苯， PhI(OPiv)2是特戊酸碘苯。
3-苯基异噻唑烷-1,1-二氧[3-Phenylisothiazolidine 1,1-dioxide]:
白色固体，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).
实施例2：
3-(4-甲基苯基)异噻唑烷-1,1-二氧[3-(4-Tolyl)isothiazolidine 1,1-dioxide]:
先称取高氯酸亚铁(5.1mg，0.02mmol)和配体L2(8.2mg,0.04mmol)于 4mL反应瓶中，加入1.0mL乙腈进行溶解，于室温下搅拌30分钟，原位络合完毕后，称取
分子筛(50.0mg)，特戊酸碘苯(163.8mg,0.4mmol)和对甲级苯丙磺酰胺底物(42.3mg,0.2mmol)，加入反应体系中，再加入1.0mL乙腈溶解，于80℃下，反应2h，过滤，滤饼用适量饱和碳酸氢钠洗涤，水相用二氯甲烷萃取3次(3×10mL)，合并有机相，饱和食盐水洗，无水硫酸钠干燥处理，脱溶剂后，柱层析分离(二氯甲烷/石油醚＝1：1～二氯甲烷)，得内磺酰胺3-(4- 甲基苯基)异噻唑烷1,1-二氧(33.7mg,80％)，白色固体。1H NMR(400MHz, CDCl3)δ7.29(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).
实施例3：
3-(4-甲氧基苯基)异噻唑烷-1,1-二氧[3-(4-Methoxyphenyl)isothiazolidine1,1-dioxide]
白色固体；产率86％；1H NMR(400MHz,CDCl3)δ7.32(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-苯基异噻唑烷-1，1-二氧[3-Phenylisothiazolidine 1,1-dioxide]
白色固体
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).
实施例4：
3-(4-硝基苯基)异噻唑烷-1,1-二氧[3-(4-Nitrophenyl)isothiazolidine 1,1-dioxide]
白色固体；产率52％；1H NMR(400MHz,CDCl3)δ8.25(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)；13CNMR(100MHz,CDCl3)δ148.0,147.9,127.0,124.5,57.2, 48.2,32.0；HRMS(ESI+)calc’dfor C9H10ClNNaO2S[M+Na]+:265.0253,found 265.0254.
实施例5：
3-(3-甲氧基苯基)异噻唑烷-1,1-二氧[3-(3-Methoxyphenyl)isothiazolidine1,1-dioxide]
白色固体；产率66％；1H NMR(400MHz,CDCl3)δ7.30(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.
实施例6：
3-(3-溴苯基)异噻唑烷-1,1-二氧[3-(3-Bromophenyl)isothiazolidine 1,1-dioxide]
白色固体；产率74％；1H NMR(400MHz,CDCl3)δ7.56(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.
实施例7：
3-(2-甲氧基苯基)异噻唑烷-1,1-二氧[3-(2-Methoxyphenyl)isothiazolidine1,1-dioxide]
白色固体；产率77％；1H NMR(400MHz,CDCl3)δ7.45(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)；13CNMR(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.
实施例8：
3-(2-溴苯基)异噻唑烷-1,1-二氧[3-(2-Bromophenyl)isothiazolidine 1,1-dioxide 2h])
白色固体；产率61％；1H NMR(400MHz,CDCl3)δ7.73(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.
实施例9：
3-(4-氯苯基)异噻唑烷-1,1-二氧[3-(4-Chlorophenyl)isothiazolidine 1,1-dioxide]
白色固体；产率80％；1H NMR(400MHz,CDCl3)δ7.34–7.32(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.
实施例10：
3-(4-溴苯基)异噻唑烷-1,1-二氧[3-(4-Bromophenyl)isothiazolidine 1,1-dioxide]
白色固体；产率75％；1H NMR(400MHz,CDCl3)δ7.50(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,found297.9512.
实施例11：
3-(4-三氟甲基苯基)异噻唑烷-1,1-二氧[3-(4-(Trifluoromethyl)phenyl)isothiazolidine 1,1-dioxide]
白色固体；产率88％；1H NMR(400MHz,CDCl3)δ7.64(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)δ144.6(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；19FNMR(376MHz,CDCl3)δ–62.61(s)； HRMS(ESI+)calc’d for C10H10F3NNaO2S[M+Na]+:288.0277,found 288.0282.
实施例12：
3-(3-甲基苯基)异噻唑烷-1,1-二氧[3-(3-Tolyl)isothiazolidine 1,1-dioxide]
白色固体；产率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).
实施例13：
3-(2-甲基苯基)异噻唑烷-1,1-二氧[3-(2-Tolyl)isothiazolidine 1,1-dioxide]
白色固体；产率81％；1H NMR(400MHz,CDCl3)δ7.58(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).
实施例14：
3-苯基-1,2-噻嗪烷-1,1-二氧[3-phenyl-1,2-thiazinane 1,1-dioxide]
白色固体；产率70％；1H NMR(400MHz,CDCl3)δ7.43–7.29(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).
实施例15：
3-甲基-2,3-二氢苯并异噻唑烷-1,1-二氧 [3-methyl-2,3-dihydrobenzo[d]isothiazole 1,1-dioxide]
白色固体；产率70％；1H NMR(400MHz,CDCl3)δ7.78(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).
实施例16：
2,3-二氢苯并异噻唑烷-1,1-二氧[2,3-Dihydrobenzo[d]isothiazole 1,1-dioxide]
白色固体；产率50％；1H NMR(400MHz,CDCl3)δ7.80(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).
实施例17:
3-((三甲基硅基)乙炔基)异噻唑烷-1,1-二氧[3-((trimethylsilyl)ethynyl)isothiazolidine 1,1-dioxide]
黄色固体；产率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 forC8H15NNaO2SSi[M+Na]+:240.0485,found 240.0489.
实施例18：
3,3-二甲基异噻唑烷-1,1-二氧[3,3-dimethylisothiazolidine 1,1-dioxide]
白色固体；产率68％；1H NMR(400MHz,CDCl3)δ4.06(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.
实施例19：
3-甲基异噻唑烷-1,1-二氧[3-methylisothiazolidine 1,1-dioxide]
白色固体；产率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).
实施例20:
方法一：先称取高氯酸亚铁(5.1mg,0.02mmol)和L1(8.1mg,0.04mmol) 于4mL反应瓶中，加入1.0mL乙腈进行溶解，于室温下搅拌30分钟，原位络合完毕后，称取
分子筛(50.0mg)，二甲基丙二酸碘苯(167.0mg,0.5mmol) 和对应的磺酰胺底物(38.6mg,0.2mmol)，加入反应体系中，再加入1.0mL乙腈溶解，于80℃下，反应2h，过滤，滤饼用适量饱和碳酸氢钠洗涤，水相用二氯甲烷萃取3次(3×10mL)，合并有机相，饱和食盐水清洗，无水硫酸钠干燥处理，脱除溶剂后，柱层析分离(二氯甲烷/石油醚＝1：1～二氯甲烷)，得五元内磺酰胺3-戊基异噻唑烷-1,1-二氧和六元内磺酰胺3-丁基异噻嗪烷-1,1-二氧为3： 5的混合物(32.6mg,85％)。
方法二：先称取高氯酸亚铁(5.1mg,0.02mmol)和L6(10.1mg,0.06mmol) 于4mL反应瓶中，加入1.0mL乙腈进行溶解，于室温下搅拌30分钟，原位络合完毕后，称取
分子筛(50.0mg)，二甲基丙二酸碘苯(162.5mg,0.5mmol) 和对应的磺酰胺底物(38.6mg,0.2mmol)，加入反应体系中，再加入1.0mL乙腈溶解，于80℃下，反应2h，过滤，滤饼用适量饱和碳酸氢钠洗涤，水相用二氯甲烷萃取3次(3×10mL)，合并有机相，饱和食盐水清洗，无水硫酸钠干燥处理，脱除溶剂后，柱层析分离(二氯甲烷/石油醚＝1：1～二氯甲烷)，得五元内磺酰胺3-戊基异噻唑烷-1,1-二氧和六元内磺酰胺3-丁基异噻嗪烷-1,1-二氧比例为2：1的混合物(28.6mg,75％)。
3-戊基异噻唑烷-1,1-二氧[3-Pentylisothiazolidine 1,1-dioxide]
无色液体；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,found214.0873.
3-丁基异噻嗪烷-1,1-二氧[3-Butyl-1,2-thiazinane 1,1-dioxide]
无色液体；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.
实施例21:
3-苯基-1，2-噻吖丁烷-1，1-二氧[3-Phenyl-1,2-thiazetidine 1,1-dioxide]
MS＝183.04
实施例22:
[Tetrahydro-1H,3H-isothiazolo[4,3-c]isothiazole 2,2,5,5-tetraoxide]
MS＝211.99
实施例23:
异噻唑烷-1，1-二氧[isothiazolidine 1,1-dioxide]
MS＝121.02
实施例24:
3-甲基-6-苯基-1，2-异噻嗪烷-1，1-二氧[3-methyl-6-phenyl-1,2-thiazinane1,1-dioxide]
MS＝225.08
实施例25:
1，2-异噻嗪烷-1，1-二氧[1,2-thiazinane 1,1-dioxide]
MS＝135.04
实施例26:
甲基-3，4，6，7，8，9-六氢-2氢化萘[2,3-e]并异噻嗪烷-3-羧基-1，1-二氧[methyl 3,4,6,7,8,9-hexahydro-2H-naphtho[2,3-e][1,2]thiazine-3-carboxylate 1,1-dioxide]
MS＝295.09
实施例27:
(E)-5-(3,5-二叔丁基-4-羟基-苯亚甲基异噻嗪烷-1，1-二氧 [(E)-5-(3,5-di-tert-butyl-4-hydroxybenzylidene)isothiazolidine 1,1-dioxide]
MS＝337.17
实施例28:
甲基异噻唑烷-3羰基-1，1-二氧[methyl isothiazolidine-3-carboxylate 1,1-dioxide]
MS＝179.03
实施例29-42:
先称取高氯酸亚铁(5.2mg,0.02mmol)和配体L2(8.0mg,0.04mmol)于4mL反应瓶中，加入1.0mL乙腈进行溶解，于室温下搅拌30分钟，原位络合完毕后，称取
分子筛(50.0mg)，特戊酸碘苯(163.8mg,0.4mmol)和相应磺酰胺H(0.2mmol)，加入反应体系中，再加入1.0mL乙腈，于80℃下反应到 TLC监测反应完全后，向反应体系中加入三氟乙酸碘苯(103.1mg，0.24mmol), 于80℃下再反应1h，然后过滤，滤饼用适量饱和碳酸氢钠洗涤，水相用二氯甲烷萃取3次(3×10mL)，合并有机相并用饱和食盐水清洗，无水硫酸钠干燥处理，脱溶剂后，柱层析分离(二氯甲烷/石油醚＝1：1～二氯甲烷)，得内磺酰亚胺类化合物G。
实施例29：
3-苯基-4,5-二氢异噻唑-1,1-二氧[3-phenyl-4,5-dihydroisothiazole 1,1-dioxide]
白色固体；产率88％；1H NMR(400MHz,CDCl3)δ8.03(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).
实施例30：
3-(4-甲基苯基)-4,5-二氢异噻唑-1,1-二氧[3-(4-Tolyl)-4,5-dihydroisothiazole 1,1-dioxide]
白色固体；1H NMR(400MHz,CDCl3)δ7.92(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).
实施例31：
3-(4-硝基苯基)-4,5-二氢异噻唑-1,1-二氧 [3-(4-Nitrophenyl)-4,5-dihydroisothiazole 1,1-dioxide]
白色固体；产率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)δ177.2,151.9,137.5,131.1,124.9,45.4,35.1；HRMS (ESI+)calc’d for C9H8N2NaO4S[M+Na]+:263.0097,found 263.0093.
实施例32：
3-(3-甲氧基苯基)-4,5-二氢异噻唑-1,1-二氧 [3-(3-Methoxyphenyl)-4,5-dihydroisothiazole 1,1-dioxide]
白色固体；产率81％；1H NMR(400MHz,CDCl3)δ7.63–7.58(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.
实施例33：
3-(3-溴苯基)-4,5-二氢异噻唑-1,1-二氧 [3-(3-Bromophenyl)-4,5-dihydroisothiazole 1,1-dioxide]
白色固体；产率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.
实施例34：
3-(2-甲氧基苯基)-4,5-二氢异噻唑-1,1-二氧 [3-(2-Methoxyphenyl)-4,5-dihydroisothiazole 1,1-dioxide]
白色固体；1H NMR(400MHz,CDCl3)δ8.15(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,found248.0352.
实施例35：
3-(2-溴苯基)-4,5-二氢异噻唑-1,1-二氧 [3-(2-Bromophenyl)-4,5-dihydroisothiazole 1,1-dioxide]
白色固体；1H NMR(400MHz,CDCl3)δ7.71(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.
实施例36：
3-(4-氯苯基)-4,5-二氢异噻唑-1,1-二氧 [3-(4-Chlorophenyl)-4,5-dihydroisothiazole 1,1-dioxide]
白色固体；产率85％；1H NMR(400MHz,CDCl3)δ7.96(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.
实施例37：
3-(4-溴苯基)-4,5-二氢异噻唑-1,1-二氧 [3-(4-Bromophenyl)-4,5-dihydroisothiazole 1,1-dioxide]
白色固体；1H NMR(400MHz,CDCl3)δ7.88(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,found295.9353.
实施例38：
3-(4-三氟甲基苯基)-4,5-二氢异噻唑-1,1-二氧[3-(4-(Trifluoromethyl)phenyl)-4,5-dihydroisothiazole 1,1-dioxide]
白色固体；产率92％；1H NMR(400MHz,CD3CN)δ8.21(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)δ177.7,135.9(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 forC10H8F3NNaO2S[M+Na]+:286.0120, found 286.0118.
实施例39：
3-(4-甲氧基苯基)-4,5-二氢异噻唑-1,1-二氧 [3-(4-Methoxyphenyl)-4,5-dihydroisothiazole 1,1-dioxide]
白色固体；产率78％；1H NMR(400MHz,CDCl3)δ7.99(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)δ175.0,164.9,131.6,123.5,114.7,55.8,44.5,33.4；HRMS (ESI+)calc’d for C10H11NNaO3S[M+Na]+:248.0352,found 248.0356.
实施例40：
3-甲基-4,5-二氢异噻唑-1,1-二氧[3-Methyl-4,5-dihydroisothiazole 1,1-dioxide]
白色固体；1H NMR(400MHz,CDCl3)δ3.31–3.24(t,2H),3.23–3.16(t,2H), 2.34(s,3H).
实施例41：
甲基-4,5-二氢异噻唑-3-羰基-1,1-二氧[methyl 4,5-dihydroisothiazole-3-carboxylate 1,1-dioxide]
MS＝177.01
实施例42：
(E)-3-(1-烯丙基)-4，5-4,5-二氢异噻唑-1,1-二氧 [(E)-3-(prop-1-en-1-yl)-4,5-dihydroisothiazole 1,1-dioxide]
MS＝159.04。
Claims (4)
1.一种内磺酰胺类化合物的制备方法，其特征在于：包括以下步骤：
将铁络合催化剂C、原料磺酰胺B、氧化剂D加入到有机溶剂中搅拌反应，反应后经过分离提纯，得到内磺酰胺类化合物E；在原料用量上，铁络合催化剂C、原料磺酰胺B、氧化剂D的物质的量比为0.01:1:1或0.5:1:5；
所制得的内磺酰胺类化合物E是以磺酰胺B为原料，反应方程式如下：
或者，将铁络合催化剂C、原料磺酰胺H、氧化剂D加入到有机溶剂中搅拌反应，检测反应完成后，再加入氧化剂F反应后，经分离纯化，得到内磺酰亚胺类化合物G；在原料用量上，所述铁络合催化剂C、原料磺酰胺H、氧化剂D、氧化剂F的物质的量比为0.01:1:1:1或0.5:1:5:2；
所制得的内磺酰胺类化合物G是以磺酰胺H为原料，反应方程式如下：
其中R1、R2、R3、R4、R5是分别独立的；n选自0、1或2；
所述R1选自氢、烷基、烯基、芳基、取代的芳基、烷氧基、酚氧基、烷硫基、酚硫基、烷基胺基或芳基氨基；
所述R2选自氢、烷基、烯基、芳基、取代的芳基、烷氧基、酚氧基、烷硫基、酚硫基、烷基胺基或芳基氨基；
所述R3选自氢、烷基、烯基、芳基；
所述R4选自氢、烷基、烯基、芳基；
所述R5选自氢、烷基、烯基、芳基、取代的芳基、烷氧基、酚氧基、烷硫基、酚硫基、烷基胺基或芳基氨基；
所述氧化剂F的结构是Ar2I(OCOCF3)2,其中Ar2选自苯基、取代的苯基、萘基、取代的萘基；
所述铁络合物催化剂C是铁盐和配体形成的络合物；其中铁盐选自三价铁盐或者二价铁盐，结构式为Fe(X)2或者Fe(X)3；X选自如***离子：Cl–、Br–、I–、AcO–、TfO–、ClO4 –、BF4 –或SbF6 –；其中配体选自如下结构：
其中R6选自氢、C1-C6的烷基、苯基或取代的苯基；其中R7、R8、R9分别是独立的取代基，相同或者不同；R7、R8、R9选自氢、C1-C6的烷基或者含氟烷基、芳基、杂芳基、烷氧基、烷基胺基、芳基氨基；其中铁和配体的物质的量的比例为1:1至1:3；
所述氧化剂D为醋酸碘苯、三氟乙酸碘苯、特戊酸碘苯、二甲基丙二酸碘苯或苯甲酸碘苯中任一种；
所述有机溶剂选自如下溶剂或者溶剂的组合：乙腈、叔丁醇、1,2-二氯乙烷、二氯甲烷、四氢呋喃、甲基叔丁基醚、二氧六环、二甲基亚砜、N、N’-二甲基甲酰胺、三氟乙醇、苯、甲苯、二甲苯或氯苯。
2.如权利要求1所述的内磺酰胺类化合物的制备方法，其特征在于：所述铁和配体的物质的量的比例为1:2。
3.如权利要求1或2所述的内磺酰胺类化合物的制备方法，其特征在于：所述搅拌反应的温度为20摄氏度至120摄氏度；所述分离提纯为柱层析、重结晶或蒸馏中任一种。
4.如权利要求3所述的内磺酰胺类化合物的制备方法，其特征在于：所述有机溶剂为乙腈或1,2-二氯乙烷。
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