CN110857281B - N-双苯磺酰基-1-苯硒基三氟乙烷衍生物及其合成方法和应用 - Google Patents
N-双苯磺酰基-1-苯硒基三氟乙烷衍生物及其合成方法和应用 Download PDFInfo
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
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- C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C323/46—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having at least one of the nitrogen atoms, not being part of nitro or nitroso groups, further bound to other hetero atoms
- C07C323/49—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having at least one of the nitrogen atoms, not being part of nitro or nitroso groups, further bound to other hetero atoms to sulfur atoms
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
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Abstract
本发明公开了一种N‑双苯磺酰基‑1‑苯硒基三氟乙烷衍生物的合成方法，以重氮化合物、二醚类化合物、N‑氟代双苯磺酰亚胺为原料，无需任何催化剂，以有机溶剂为溶剂，经过一步反应，得到所述N‑双苯磺酰基‑1‑苯硒基三氟乙烷衍生物。本发明N‑双苯磺酰基‑1‑苯硒基三氟乙烷衍生物的合成方法具有高效的原子经济性，无需任何有机催化剂或金属催化剂，操作简单安全，合成得到的N‑双苯磺酰基‑1‑苯硒基三氟乙烷衍生物是重要的有机合成、医药中间体。
Description
技术领域
本发明属于合成医药、化工领域，主要涉及N-双苯磺酰基-1-苯硒基三氟乙烷衍生物及其合成方法和应用。
背景技术
含硒类与三氟甲基类化合物具有很好的生物活性，此外，有机硒类化合物具有重要的物理和药物活性，被广泛地应用于材料科学和药物设计。构筑同时具有硒与三氟甲基结构的化合物可以提供或开发更多具有该类结构的特殊性质。由于该类产物所含活性官能团较多，难以合成，因此，还没有发现该类结构的产物的合成方法。
发明内容
本发明填补了该类化合物合成方法的空白，提出了一步合成同时具有含氮与硒的三氟甲基类化合物的合成方法，具有原料简单易得、操作简便、条件温和、无需金属催化剂、高收率等优点。利用本发明合成方法具有较高的收率。本发明合成得到的N-双苯磺酰基-1-苯硒基三氟乙烷衍生物具有高效原子经济性等优点。
本发明提出了一种如式(4)所示的N-双苯磺酰基-1-苯硒基三氟乙烷衍生物，其结构如式(4)所示：
R1为氟取代的C1-C10烷基、磷酸酯基、C1-C10烷基取代的磷酸酯基、酯基、C1-C10烷基取代的酯基、苄基酯基、异丙基羰基、环己基羰基；其中，所述氟取代的C1-C10烷基可以是一氟、二氟等多氟取代C1-C10烷基；
X为硫、硒、碲；
R2为苯基、C1-C10烷基取代的苯基、卤素取代的苯基、氰基取代的苯基、萘基、噻吩基、吡啶基、C1-C10烷基。
优选地，
R1为二氟甲基、三氟甲基、五氟乙基、乙基磷酸酯基、乙基酯基、苄基酯基、异丙基羰基、环己基羰基；
X为硫、硒、碲；
R2为苯基、邻甲基苯基、间甲基苯基、对甲基苯基、对溴苯基、对氯苯基、对氰基苯基、2-萘基、3-噻吩基、3-吡啶基、正庚基。
本发明还提出了一种如式(4)所示的N-双苯磺酰基-1-苯硒基三氟乙烷衍生物的合成方法，以重氮化合物、二醚类化合物、N-氟代双苯磺酰亚胺为原料，无需任何催化剂，以有机溶剂为溶剂，经过一步反应，得到所述N-双苯磺酰基-1-苯硒基三氟乙烷衍生物；
所述合成反应过程如反应式(I)所示：
式(4)及反应式(I)中，R1为氟取代的C1-C10烷基、磷酸酯基、C1-C10烷基取代的磷酸酯基、酯基、C1-C10烷基取代的酯基、苄基酯基、异丙基羰基、环己基羰基；其中，所述氟取代的C1-C10烷基可以是一氟、二氟等多氟取代C1-C10烷基；
X为硫、硒、碲；
R2为苯基、烷基取代的苯基、卤素取代的苯基、氰基取代的苯基、萘基、噻吩基、吡啶基、C1-C10烷基。
优选地，
R1为：二氟甲基、三氟甲基、五氟乙基、乙基磷酸酯基、乙基酯基、苄基酯基、异丙基羰基、环己基羰基；
X为硫、硒、碲；
R2为苯基、邻甲基苯基、间甲基苯基、对甲基苯基、对溴苯基、对氯苯基、对氰基苯基、2-萘基、3-噻吩基、3-吡啶基、正庚基。
本发明中，所述方法具体包括以下步骤：先将二醚类化合物和N-氟代双苯磺酰亚胺溶于有机溶剂中形成第一混合溶液，然后将重氮化合物溶于前述有机溶剂中形成第二混合溶液，然后将第一、第二混合溶液混合，反应得到所述N-双苯磺酰基-1-苯硒基三氟乙烷衍生物。
本发明中，所述原料的摩尔比为重氮化合物：二醚类化合物：N-氟代双苯磺酰亚胺＝(2-3)：(0.6-1)：(1)；优选地，为2:0.6:1。
本发明中，所述有机溶剂为氯代烷烃、醚类、甲苯，其中，所述卤代烷烃为二氯甲烷、三氯甲烷、1,2-二氯乙烷等中的一种或多种；所述醚类为乙醚、四氢呋喃、1，4二氧六环等中的一种或多种。
优选地，所述有机溶剂为二氯甲烷、甲苯。
本发明中，所述反应的温度为0℃-40℃；优选地，为25℃。
本发明中，所述反应的时间为10min-12h；优选地，为10min。
本发明在制备得到所述N-双苯磺酰基-1-苯硒基三氟乙烷衍生物后还包括分离纯化的步骤。
其中，所述分离纯化是用体积比为1:(40～20)的乙酸乙酯和石油醚的混合溶液进行柱层析。
本发明首次开发了三氟甲基重氮的双官能团化：无需添加任何催化剂或添加剂，通过简单易得的原料，在温和的反应条件下高效构建含有氮、硒杂原子的三氟甲基类化合物。区别于现有技术中需要重金属或者贵金属催化合成手段与反应机理，本发明通过更加高效的绿色方法，合成了一系列含硒的三氟甲基类化合物。值得注意的是，在合成反应中，二醚类化合物只需其它投料的一半即可，大大提高了反应的原子经济性。
本发明还提出了由上述制备方法制备得到的N-双苯磺酰基-1-苯硒基三氟乙烷衍生物。
本发明还提出了N-双苯磺酰基-1-苯硒基三氟乙烷衍生物在有机合成中的应用。
本发明所提出的具有含氮与硒的N-双苯磺酰基-1-苯硒基三氟乙烷衍生物的化学合成方法，以重氮化合物、二醚类化合物和N-氟代双苯磺酰亚胺为原料，无需任何有机或金属催化剂，以有机溶剂为溶剂，经过一步三组分反应得到产物。
本发明合成方法所涉及的化学机理如下所示：二醚类化合物与N-氟代双苯磺酰亚胺在室温下迅速反应形成活泼中间体I(久至空气中不稳定)和氟化硒II；氟化硒与N-氟代双苯磺酰亚胺进一步反应形成活泼中间体I，并放出无机形态氟；活泼中间体I中带正电部分的Se与重氮的中心碳原子反应，促进重氮的分解，随之带负电部分的N进攻中心碳原子，得到目标产物。这是一种全新的非共轭类重氮双官能团化的合成方法。
本发明采用一步三组分反应得到式(4)所示的产物。由于多组分反应具有高灵活性，高选择性，高效原子经济性，易操作性等特点，近年来随着原子经济性概念的日益发展，多组分反应越来越成为研究的热点。将多组分反应应用于药物合成领域具有很广阔的前景。本发明用重氮化合物、二醚类化合物、N-氟代双苯磺酰亚胺为原料，无需催化剂，该反应以有机溶剂为溶剂，一步制备出一系列的同时含硒与三氟甲基类衍生物。
本发明有益效果还包括，能够通过一步反应构建具有光学活性的N-双苯磺酰基-1-苯硒基三氟乙烷衍生物，具有高效原子经济性，高普适性，高收率等优点，并且操作简单安全。本发明无需任何催化剂首次实现了非共轭类重氮的双官能团化，通过简单易得的原料，一步高效构建了同时具有硒与三氟甲基类衍生物。
附图说明
图1所示为本发明实施例1N-双苯磺酰基-1-苯硒基三氟乙烷衍生物的核磁共振1HNMR(图1A)、13C NMR(图1B)、19F NMR图谱(图1C)。
图2所示为本发明实施例2N-双苯磺酰基-1-苯硒基三氟乙烷衍生物的核磁共振1HNMR(图2A)、13C NMR(图2B)、19F NMR图谱(图2C)。
图3所示为本发明实施例3N-双苯磺酰基-1-苯硒基三氟乙烷衍生物的核磁共振1HNMR(图3A)、13C NMR(图3B)、19F NMR图谱(图3C)。
图4所示为本发明实施例4N-双苯磺酰基-1-苯硒基三氟乙烷衍生物的核磁共振1HNMR(图4A)、13C NMR(图4B)、31P NMR图谱(图4C)。
图5所示为本发明实施例5N-双苯磺酰基-1-苯硒基三氟乙烷衍生物的核磁共振1HNMR(图5A)、13C NMR图谱(图5B)。
图6所示为本发明实施例6N-双苯磺酰基-1-苯硒基三氟乙烷衍生物的核磁共振1HNMR(图6A)、13C NMR(图6B)、19F NMR图谱(图6C)。
图7所示为本发明实施例7N-双苯磺酰基-1-苯硒基三氟乙烷衍生物的核磁共振1HNMR(图7A)、13C NMR图谱(图7B)。
图8所示为本发明实施例8N-双苯磺酰基-1-苯硒基三氟乙烷衍生物的核磁共振1HNMR(图8A)、13C NMR(图8B)、19F NMR图谱(图8C)。
图9所示为本发明实施例9N-双苯磺酰基-1-苯硒基三氟乙烷衍生物的核磁共振1HNMR(图9A)、13C NMR(图9B)、19F NMR图谱(图9C)。
具体实施方式
结合以下具体实施例和附图，对本发明作进一步的详细说明，本发明的保护内容不局限于以下实施例。在不背离发明构思的精神和范围下，本领域技术人员能够想到的变化和优点都被包括在本发明中，并且以所附的权利要求书为保护范围。
实施例1：
N-氟代双苯磺酰亚胺(0.2mmol)，二苯基二硒醚(0.12mmol)溶于二氯甲烷(2.0mL)，然后，将稀释在二氯甲烷(1mL)的三氟甲基重氮的甲苯溶液(c＝0.85mmol/mL,0.4mmol)缓慢滴加到反应体系中，反应体系在室温(25℃)下，滴加完毕后，搅拌10分钟，减压除去溶剂，得到粗产物，其结构如式(4-1)所示。将粗产物进行柱层析(乙酸乙酯:石油醚＝1:40～1:20)得到纯产品。产率为95％。核磁共振1H NMR、13C NMR、19F NMR图谱如图1所示，1H NMR(400MHz,CDCl3):δ8.23(d,J＝8.2Hz,2H),7.87(d,J＝8.2Hz,2H),7.71-7.57(m,4H),7.46-7.42(m,2H),7.36-7.32(m,3H),7.27-7.23(m,2H),5.54(q,J＝8.0Hz,1H)ppm；13CNMR(100MHz,CDCl3):δ139.9,138.0,134.9,134.6,134.5,129.7,129.6,129.4,129.3,128.9,128.8,123.5(q,JCF＝280.3Hz),60.2(q,JCF＝36.5Hz)ppm；19F NMR(376MHz,CDCl3)δ-67.03ppm.
实施例2：
N-氟代双苯磺酰亚胺(0.2mmol)，二苯基二硒醚(0.12mmol)溶于二氯甲烷(2.0mL)，然后，将稀释在二氯甲烷(1mL)的五氟乙基重氮的甲苯溶液(c＝0.85mmol/mL,0.4mmol)缓慢滴加到反应体系中，反应体系在室温(25℃)下，滴加完毕后，搅拌10分钟，减压除去溶剂，得到粗产物，其结构如式(4-2)所示。将粗产物进行柱层析(乙酸乙酯:石油醚＝1:40～1:20)得到纯产品。产率为88％。核磁共振1H NMR、13C NMR、19F NMR图谱如图2所示，1H NMR(400MHz,CDCl3):δ8.40(d,J＝7.8Hz,2H),7.90(d,J＝7.9Hz,2H),7.71(t,J＝7.4Hz,1H),7.62(q,J＝7.8Hz,3H),7.45(t,J＝7.8Hz,2H),7.40-7.32(m,3H),7.31-7.25(m,2H),5.96(dd,J＝20.0,6.9Hz,1H)ppm；13C NMR(100MHz,CDCl3):δ139.86,138.04,134.97,134.61,134.47,130.11,129.63,129.46,129.01,128.97,128.76,128.40,58.95(dd,JCF＝28.9,20.6Hz)ppm(部分碳因氟原子对其耦合，产生多重裂分无法表述)；19F NMR(376MHz,CDCl3):δ-81.70(3F),-107.99(d,J＝264.8Hz,2F),-110.24(d,J＝264.8Hz,2F)ppm.
实施例3：
N-氟代双苯磺酰亚胺(0.2mmol)，二苯基二硒醚(0.12mmol)溶于二氯甲烷(2.0mL)，然后，将稀释在二氯甲烷(1mL)的二氟甲基重氮的氯仿溶液(c＝0.85mmol/mL,0.4mmol)缓慢滴加到反应体系中，反应体系在室温(25℃)下，滴加完毕后，搅拌10分钟，减压除去溶剂，得到粗产物，其结构如式(4-3)所示。将粗产物进行柱层析(乙酸乙酯:石油醚＝1:40～1:20)得到纯产品。产率为85％。核磁共振1H NMR、13C NMR、19F NMR图谱如图3所示，1H NMR(400MHz,CDCl3):δ8.12(d,J＝7.6Hz,2H),7.70(d,J＝7.6Hz,2H),7.59-7.41(m,5H),7.29(d,J＝7.9Hz,3H),7.20(t,J＝7.3Hz,1H),7.12(t,J＝7.4Hz,2H),6.44-6.13(m,1H),5.23-5.11(m,1H)ppm；13C NMR(100MHz,CDCl3):δ139.74,138.72,137.84,134.84,134.46,129.45,129.38,129.27,129.21,129.09,129.00,128.95,128.83,128.67,114.62(dd,JCF＝256.1,243.9Hz),62.79(dd,JCF＝37.0,20.9Hz)ppm；19F NMR(376MHz,CDCl3):δ-112.62(d,J＝275.2Hz),-120.77(d,J＝275.2Hz)ppm.
实施例4：
N-氟代双苯磺酰亚胺(0.2mmol)，二苯基二硒醚(0.12mmol)溶于二氯甲烷(2.0mL)，然后，将稀释在二氯甲烷(1mL)的亚磷酸乙酯甲基重氮(0.4mmol)缓慢滴加到反应体系中，反应体系在室温(25℃)下，滴加完毕后，搅拌10分钟，减压除去溶剂，得到粗产物，其结构如式(4-4)所示。将粗产物进行柱层析(乙酸乙酯:石油醚＝1:30～1:20)得到纯产品。产率为90％。核磁共振1H NMR、13C NMR、31PNMR图谱如图4所示，1H NMR(400MHz,CDCl3):δ8.45(d,J＝7.7Hz,2H),7.83(d,J＝7.7Hz,2H),7.70(t,J＝7.2Hz,1H),7.62-7.57(m,3H),7.46(d,J＝7.2Hz,2H),7.39(t,J＝7.7Hz,2H),7.33(d,J＝6.9Hz,1H),7.31-7.25(m,2H),5.77(d,J＝19.0Hz,1H),4.25-4.11(m,4H),1.31-1.24(m,6H)ppm；13C NMR(100MHz,CDCl3):δ140.0,138.4,134.2,134.1,134.0,130.2(d,JCP＝5.2Hz),130.1,129.3,128.9,128.7,128.6,127.4,64.2(dd,JCP＝15.0,7.0Hz),56.8,55.1,16.3(d,JCP＝6.1Hz),16.2(d,JCP＝6.3Hz)ppm；31P NMR(162MHz,CDCl3):δ15.68ppm.
实施例5：
N-氟代双苯磺酰亚胺(0.2mmol)，二苯基二硒醚(0.12mmol)溶于二氯甲烷(2.0mL)，然后，将稀释在二氯甲烷(1mL)的重氮乙酸乙酯(0.4mmol)缓慢滴加到反应体系中，反应体系在室温(25℃)下，滴加完毕后，搅拌10分钟，减压除去溶剂，得到粗产物，其结构如式(4-5)所示。将粗产物进行柱层析(乙酸乙酯:石油醚＝1:40～1:20)得到纯产品。产率为88％。核磁共振1H NMR、13C NMR图谱如图5所示，1H NMR(400MHz,CDCl3):δ8.24-8.03(m,4H),7.64(t,J＝7.2Hz,2H),7.57-7.50(m,4H),7.46(d,J＝7.4Hz,2H),7.35-7.30(m,1H),7.27-7.24(m,2H),5.91(s,1H),4.12-4.06(m,1H),4.04-3.93(m,1H),1.08(t,J＝7.0Hz,3H)ppm；13C NMR(100MHz,CDCl3):δ167.6,135.3,134.2,129.7,129.4,129.3,129.1,129.0,128.8,62.9,60.1,13.8ppm.
实施例6：
N-氟代双苯磺酰亚胺(0.2mmol)，二庚基二硒醚(0.12mmol)溶于二氯甲烷(2.0mL)，然后，将稀释在二氯甲烷(1mL)的三氟甲基重氮的甲苯溶液(c＝0.85mmol/mL,0.4mmol)缓慢滴加到反应体系中，反应体系在室温(25℃)下，滴加完毕后，搅拌10分钟，减压除去溶剂，得到粗产物，其结构如式(4-6)所示。将粗产物进行柱层析(乙酸乙酯:石油醚＝1:40～1:20)得到纯产品。产率为75％。核磁共振1H NMR、13C NMR、19F NMR图谱如图6所示，1H NMR(400MHz,CDCl3):δ8.28(d,J＝8.0Hz,2H),8.07(d,J＝7.7Hz,2H),7.72-7.66(m,2H),7.61-7.55(m,4H),5.59(q,J＝8.3Hz,1H),2.75-2.68(m,1H),2.55-2.48(m,1H),1.59-1.54(m,2H),1.29-1.26(m,8H),0.89(t,J＝6.7Hz,3H)ppm；13C NMR(100MHz,CDCl3):δ140.1,138.3,134.6,134.2,129.5,129.2,128.8,128.7,123.3(q,JCF＝281.6Hz),55.7(q,JCF＝37.1Hz),31.6,29.6,29.5,28.7,28.1,22.5,14.0ppm；19F NMR(376MHz,CDCl3):δ-66.18ppm.
实施例7：
N-氟代双苯磺酰亚胺(0.2mmol)，二苯基二硒醚(0.12mmol)溶于二氯甲烷(2.0mL)，然后，将稀释在二氯甲烷(1mL)的异丙基羰基重氮甲烷(0.4mmol)缓慢滴加到反应体系中，反应体系在室温(25℃)下，滴加完毕后，搅拌10分钟，减压除去溶剂，得到粗产物，其结构如式(4-7)所示。将粗产物进行柱层析(乙酸乙酯:石油醚＝1:40～1:20)得到纯产品。产率为93％。核磁共振1HNMR、13C NMR图谱如图7所示，1H NMR(400MHz,CDCl3):δ8.15(s,4H),7.66-7.60(m,4H),7.54-7.50(m,4H),7.40-7.32(m,3H),5.81(s,1H),3.13-2.98(m,1H),1.13(d,J＝6.6Hz,3H),0.64(d,J＝6.9Hz,3H)ppm；13C NMR(100MHz,CDCl3):δ202.7,134.1,134.1,131.1,129.9,129.1,128.9,66.4,35.8,19.6,19.1ppm.
实施例8：
N-氟代双苯磺酰亚胺(0.2mmol)，二苯基二硫醚(0.12mmol)溶于二氯甲烷(2.0mL)，然后，将稀释在二氯甲烷(1mL)的三氟甲基重氮的甲苯溶液(c＝0.85mmol/mL,0.4mmol)缓慢滴加到反应体系中，反应体系在室温(25℃)下，滴加完毕后，搅拌过夜，减压除去溶剂，得到粗产物，其结构如式(4-8)所示。将粗产物进行柱层析(乙酸乙酯:石油醚＝1:40～1:20)得到纯产品。产率为80％。核磁共振1H NMR、13C NMR、19F NMR图谱如图8所示，1HNMR(400MHz,CDCl3):δ8.30(d,J＝8.0Hz,2H),7.87(d,J＝8.0Hz,2H),7.72-7.68(m,1H),7.64-7.57(m,3H),7.46-7.42(m,2H),7.36(t,J＝7.1Hz,1H),7.30-7.20(m,4H),5.76(q,J＝7.6Hz,1H)ppm；13C NMR(100MHz,CDCl3):δ140.1,138.3,134.6,134.4,133.3,132.9,129.7,129.6,129.4,129.1,128.9,128.8,123.1(q,JCF＝281.5Hz),70.4(q,JCF＝36.0Hz)ppm；19F NMR(470MHz,CDCl3):δ-66.92ppm.
实施例9：
N-氟代双苯磺酰亚胺(0.2mmol)，二苯基二碲醚(0.12mmol)溶于二氯甲烷(2.0mL)，然后，将稀释在二氯甲烷(1mL)的三氟甲基重氮的甲苯溶液(c＝0.85mmol/mL,0.4mmol)缓慢滴加到反应体系中，反应体系在室温(25℃)下，滴加完毕后，搅拌10分钟，减压除去溶剂，得到粗产物，其结构如式(4-9)所示。将粗产物进行柱层析(乙酸乙酯:石油醚＝1:40～1:20)得到纯产品。产率为85％。核磁共振1H NMR、13C NMR、19F NMR图谱如图9所示，1H NMR(400MHz,CDCl3):δ8.16(d,J＝8.1Hz,2H),7.90(d,J＝8.1Hz,2H),7.68(t,J＝7.4Hz,2H),7.58-7.55(m,4H),7.48(t,J＝7.7Hz,2H),7.37(t,J＝7.3Hz,1H),7.22(t,J＝7.5Hz,2H),5.30(q,J＝8.7Hz,1H)ppm；13C NMR(100MHz,CDCl3):δ140.1,139.7,137.7,134.7,134.6,129.6,129.4,129.1,129.0,128.9,124.3(q,JCF＝280.5Hz),115.9,38.4(q,JCF＝36.1Hz)ppm；19F NMR(470MHz,CDCl3):δ-67.00ppm.
实施例10：
本实施例实验方法基本与实施例8相同，本实施例中所采用的硫醚为二对甲苯基二硫醚，所得到的产物如结构式(4-10)所示。产率为85％。1H NMR(400MHz,CDCl3):δ8.33(d,J＝8.0Hz,2H),7.90(d,J＝8.0Hz,2H),7.73-7.59(m,4H),7.47(t,J＝7.7Hz,2H),7.10(q,J＝8.1Hz,4H),5.71(q,J＝7.6Hz,1H),2.34(s,3H)ppm；13C NMR(100MHz,CDCl3):δ140.2,139.8,138.4,134.5,134.4,133.7,130.3,129.7,129.2,129.1,128.8,123.1(q,JCF＝281.7Hz),70.7(q,JCF＝35.8Hz),21.2ppm；19F NMR(470MHz,CDCl3):δ-66.84ppm.
实施例11：
本实施例实验方法基本与实施例8相同，本实施例中所采用的硫醚为二对氯苯基二硫醚，所得到的产物如结构式(4-11)所示。产率为75％。1H NMR(400MHz,CDCl3):δ8.30(d,J＝7.7Hz,2H),7.90(d,J＝7.7Hz,2H),7.73-7.70(m,1H),7.68-7.59(m,3H),7.48(t,J＝7.7Hz,2H),7.24(d,J＝8.3Hz,2H),7.14(d,J＝8.1Hz,2H),5.66(q,J＝7.5Hz,1H)ppm；13CNMR(100MHz,CDCl3):δ140.0,138.2,136.0,134.8,134.7,134.5,131.1,129.8,129.7,129.2,128.9,128.8,122.9(q,JCF＝283.4Hz),70.3(q,JCF＝36.4Hz)ppm；19F NMR(470MHz,CDCl3):δ-66.83ppm.
实施例12：
本实施例实验方法基本与实施例5相同，本实施例中所采用的重氮为重氮乙酸苄酯，所得到的产物如结构式(4-12)所示。产率为85％。1H NMR(400MHz,CDCl3):δ8.21-7.95(m,4H),7.55(t,J＝7.4Hz,2H),7.44-7.35(m,6H),7.33-7.28(m,4H),7.23-7.16(m,4H),5.92(s,1H),5.02(s,2H)ppm；13C NMR(100MHz,CDCl3):δ167.6,135.4,134.7,134.2,129.6,129.3,129.0,128.8,128.6,128.5,128.5,68.6,59.8ppm.
实施例13：
本实施例实验方法基本与实施例7相同，本实施例中所采用的重氮为环己基羰基重氮甲烷，所得到的产物如结构式(4-13)所示。产率为90％。1H NMR(400MHz,CDCl3):δ8.15(s,4H),7.67-7.60(m,4H),7.55-7.51(m,4H),7.41-7.33(m,3H),5.79(s,1H),2.77(t,J＝11.3Hz,1H),1.93(d,J＝12.9Hz,1H),1.74(d,J＝12.4Hz,1H),1.56(t,J＝11.1Hz,2H),1.40-1.31(m,1H),1.21-1.07(m,3H),1.00-0.91(m,1H),0.88-0.79(m,1H)ppm；13C NMR(100MHz,CDCl3):δ201.7,134.3,134.1,131.2,129.8,129.1,128.9,66.4,45.8,29.7,28.9,25.6,25.5,25.4ppm.
实施例14：
本实施例实验方法基本与实施例1相同，本实施例中所采用的硒醚为二对甲苯基二硒醚，所得到的产物如结构式(4-14)所示。产率为95％。1H NMR(400MHz,CDCl3):δ8.24(d,J＝8.0Hz,2H),7.89(d,J＝8.0Hz,2H),7.74-7.62(m,2H),7.57(t,J＝7.6Hz,2H),7.46(t,J＝7.6Hz,2H),7.21(d,J＝7.6Hz,2H),7.05(d,J＝7.6Hz,2H),5.50(q,J＝8.0Hz,1H),2.34(s,3H)ppm；13C NMR(100MHz,CDCl3):δ139.9,139.6,138.1,135.2,134.6,134.5,130.3,129.4,129.3,128.9,128.8,126.0,123.6(q,JCF＝281.9Hz),60.4(q,JCF＝36.2Hz),21.3ppm；19F NMR(470MHz,CDCl3):δ-66.96ppm.
实施例15：
本实施例实验方法基本与实施例1相同，本实施例中所采用的硒醚为二间甲基二硒醚，所得到的产物如结构式(4-15)所示。产率为92％。1H NMR(400MHz,CDCl3):δ8.25(d,J＝8.0Hz,2H),7.89(d,J＝7.9Hz,2H),7.72-7.64(m,2H),7.60(t,J＝7.5Hz,2H),7.45(t,J＝7.5Hz,2H),7.16-7.14(m,4H),5.57(q,J＝8.0Hz,1H),2.31(s,3H)ppm；13C NMR(100MHz,CDCl3):δ139.9,139.3,138.0,135.3,134.5,134.5,131.8,130.1,129.4,129.4,129.2,128.9,128.8,128.7,123.5(q,JCF＝281.9Hz),60.1(q,JCF＝36.4Hz),21.3ppm；19F NMR(470MHz,CDCl3):δ-66.97ppm.
实施例16：
本实施例实验方法基本与实施例1相同，本实施例中所采用的硒醚为二对溴苯基二硒醚，所得到的产物如结构式(4-16)所示。产率为90％。1H NMR(400MHz,CDCl3):δ8.23(d,J＝7.9Hz,2H),7.91(d,J＝7.9Hz,2H),7.75-7.65(m,2H),7.60(t,J＝7.7Hz,2H),7.49(t,J＝7.7Hz,2H),7.38(d,J＝8.1Hz,2H),7.18(d,J＝8.1Hz,2H),5.45(q,J＝7.9Hz,1H)ppm；13CNMR(100MHz,CDCl3):δ139.7,137.8,136.6,134.7,134.6,132.7,129.3,129.0,128.8,128.3,124.1,123.4(q,JCF＝282.0Hz),60.2(q,JCF＝36.6Hz)ppm；19F NMR(376MHz,CDCl3):δ-66.93ppm.
实施例17：
本实施例实验方法基本与实施例1相同，本实施例中所采用的硒醚为二β-吡啶基二硒醚，所得到的产物如结构式(4-17)所示。产率为88％。1H NMR(400MHz,CDCl3):δ8.59(d,J＝4.6Hz,1H),8.41(s,1H),8.21(d,J＝8.0Hz,2H),7.89(d,J＝8.0Hz,2H),7.70-7.69(m,3H),7.59(t,J＝7.6Hz,2H),7.50(t,J＝7.5Hz,2H),7.24-7.17(m,1H),5.39(q,J＝7.8Hz,1H)ppm；13C NMR(100MHz,CDCl3):δ154.8,150.3,142.6,139.6,137.7,135.0,134.7,129.4,129.3,129.0,128.8,126.7,124.4,123.2(q,JCF＝280.2Hz),59.9(q,JCF＝36.9Hz)ppm；19FNMR(376MHz,CDCl3):δ-67.04ppm.
实施例18：
本实施例实验方法参考与实施例1相同，本实施例中所采用的硒醚为二邻甲苯基二硒醚，所得到的产物如结构式(4-18)所示。产率为90％。1H NMR(400MHz,CDCl3):δ8.29(d,J＝7.9Hz,2H),7.80(d,J＝7.9Hz,2H),7.69(t,J＝7.3Hz,1H),7.58(t,J＝7.9Hz,3H),7.36(t,J＝8.5Hz,3H),7.23(d,J＝7.0Hz,1H),7.17(d,J＝7.3Hz,1H),7.10(t,J＝7.4Hz,1H),5.64(q,J＝8.0Hz,1H),2.26(s,3H)ppm；13C NMR(100MHz,CDCl3):δ141.3,139.9,137.9,135.1,134.5,130.8,130.5,129.6,129.5,129.1,128.9,128.7,127.4,123.4(q,JCF＝282.1Hz),60.3(q,JCF＝36.6Hz),22.9ppm；19F NMR(376MHz,CDCl3):δ-66.45ppm.
实施例19：
本实施例实验方法与实施例1相同，本实施例中所采用的硒醚为二β-萘基二硒醚，所得到的产物如结构式(4-19)所示。产率为80％。1H NMR(400MHz,CDCl3):δ8.27(d,J＝8.0Hz,2H),8.08(d,J＝7.9Hz,1H),7.84(d,J＝7.9Hz,2H),7.81(s,1H),7.76-7.70(m,3H),7.63-7.58(m,2H),7.56-7.52(m,3H),7.44(d,J＝8.5Hz,1H),7.31(t,J＝7.7Hz,2H),5.65(q,J＝8.0Hz,1H)ppm；13C NMR(100MHz,CDCl3):δ140.0,139.0,137.9,134.7,134.5,134.4,133.5,133.1,131.0,129.4,129.3,129.2,129.1,128.9,128.8,128.7,127.9,127.8,127.2,126.9,123.5(q,JCF＝282.1Hz),60.2(q,JCF＝36.4Hz)ppm；19F NMR(376MHz,CDCl3):δ-66.90ppm.
实施例20：
本实施例实验方法与实施例1相同，本实施例中所采用的硒醚为二β-噻吩基二硒醚，所得到的产物如结构式(4-20)所示。产率为80％。1H NMR(400MHz,CDCl3):δ8.24(d,J＝7.8Hz,2H),7.93(d,J＝7.7Hz,2H),7.72-7.67(m,2H),7.59(t,J＝7.7Hz,2H),7.51(t,J＝7.8Hz,2H),7.31-7.29(m,1H),7.20(d,J＝1.6Hz,1H),6.93(d,J＝4.8Hz,1H),5.45(q,J＝8.0Hz,1H)ppm；13C NMR(100MHz,CDCl3):δ139.8,138.1,134.7,134.5,132.7,131.7,129.3,129.3,128.9,128.8,127.2,123.4(q,JCF＝282.0Hz),123.0,60.2(q,JCF＝36.4Hz)ppm；19FNMR(376MHz,CDCl3):δ-67.13ppm.
实施例21：
本实施例实验方法与实施例1相同，本实施例中所采用的硒醚为二对氰基苯基二硒醚，所得到的产物如结构式(4-21)所示。产率为70％。1H NMR(400MHz,CDCl3):δ8.22(d,J＝7.9Hz,2H),7.89(d,J＝7.9Hz,2H),7.76-7.65(m,2H),7.65-7.59(m,2H),7.55(d,J＝8.0Hz,2H),7.51-7.42(m,4H),5.57(q,J＝7.8Hz,1H)ppm；13C NMR(100MHz,CDCl3):δ138.6,136.8,135.0,133.8,133.7,133.5,131.8,128.3,128.2,128.0,127.8,122.1(q,JCF＝282.2Hz),116.9,111.8,58.8(q,JCF＝37.1Hz)ppm；19F NMR(376MHz,CDCl3):δ-66.99ppm.
本发明的保护内容不局限于以上实施例。在不背离本发明构思的精神和范围下，本领域技术人员能够想到的变化和优点都被包括在本发明中，并且以所附的权利要求书为保护范围。
Claims (8)
1.一种式(4)化合物的合成方法，其特征在于，所述方法以重氮化合物、二醚类化合物、N-氟代双苯磺酰亚胺为原料，以有机溶剂为溶剂，经过一步反应，得到如式(4)所示的化合物；所述反应过程如反应式(I)所示：
其中，R1为氟取代的C1-C10烷基、C1-C10烷基取代的磷酸酯基、C1-C10烷基取代的酯基、苄基酯基、异丙基羰基、环己基羰基；
X为硫、硒、碲；
R2为苯基、C1-C10烷基取代的苯基、卤素取代的苯基、氰基取代的苯基、萘基、噻吩基、吡啶基、C1-C10烷基。
2.如权利要求1所述的合成方法，其特征在于，R1为二氟甲基、三氟甲基、五氟乙基、乙基磷酸酯基、乙基酯基、苄基酯基、异丙基羰基、环己基羰基；X为硫、硒、碲；R2为苯基、邻甲基苯基、间甲基苯基、对甲基苯基、对溴苯基、对氯苯基、对氰基苯基、2-萘基、3-噻吩基、3-吡啶基、正庚基。
3.如权利要求1所述的合成方法，其特征在于，所述方法具体包括以下步骤：先将所述二醚类化合物、N-氟代双苯磺酰亚胺溶于所述有机溶剂中形成第一混合溶液，然后将重氮化合物溶于前述有机溶剂中形成第二混合溶液，然后将第一、第二混合溶液混合，反应得到式(4)所示的化合物。
4.如权利要求1所述的合成方法，其特征在于，所述原料的摩尔比为重氮化合物：二醚类化合物：N-氟代双苯磺酰亚胺＝(2-3)：(0.6-1.0)：(1)。
5.如权利要求1所述的合成方法，其特征在于，所述原料的摩尔比为重氮化合物：二醚类化合物：N-氟代双苯磺酰亚胺＝2:0.6:1。
6.如权利要求1所述的合成方法，其特征在于，所述有机溶剂为氯代烷烃、醚类、甲苯；其中，所述氯代烷烃选自二氯甲烷、三氯甲烷、1,2-二氯乙烷中的一种或多种；所述醚类选自乙醚、四氢呋喃、1,4-二氧六环中的一种或多种。
7.如权利要求1所述的合成方法，其特征在于，所述反应的温度为0℃-40℃。
8.如权利要求1所述的合成方法，其特征在于，在反应得到所述式(4)化合物后还包括分离纯化的步骤；所述分离纯化是用体积比为1:(40～20)的乙酸乙酯和石油醚的混合溶液进行柱层析。
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