一种α,α-二氯或α,α-二溴取代的亚胺化合物及制备方法
阅读说明：本技术 一种α,α-二氯或α,α-二溴取代的亚胺化合物及制备方法 (Alpha, alpha-dichloro or alpha, alpha-dibromo substituted imine compound and preparation method thereof ) 是由 李方怿 邱昌福 梁柳艺 赫文迪 王春华 李正 于 2019-10-09 设计创作，主要内容包括：本发明涉及一种α,α-二氯或α,α-二溴取代的亚胺化合物及制备方法。该制备方法包含下列步骤：将如式A所示烯胺化合物溶于有机溶剂中,再加入氯化试剂或溴化试剂,待反应完全后,经过滤、洗涤、分离等操作或其中部分操作得到如式B或C所对应的二氯或二溴取代的亚胺化合物。本发明的制备方法操作简单,原料简单易得,反应步骤少,转化率和反应收率高,官能团兼容性好,底物适用范围广,可避免使用碱和贵金属,绿色环保。所得化合物含有亚胺、二氯亚甲基和二溴亚甲基结构,可作为活性分子的重要合成砌块,在生物医药领域具有较大的应用前景。(The invention relates to an alpha, alpha-dichloro or alpha, alpha-dibromo substituted imine compound and a preparation method thereof. The preparation method comprises the following steps: dissolving enamine compound shown in formula A in organic solvent, adding a chlorination reagent or a bromination reagent, after the reaction is completed, filtering, washing, separating and the like or partially operating the mixture to obtain dichloro or dibromo substituted imine compound corresponding to formula B or C. The preparation method disclosed by the invention is simple to operate, the raw materials are simple and easy to obtain, the reaction steps are few, the conversion rate and the reaction yield are high, the compatibility of functional groups is good, the application range of the substrate is wide, the use of alkali and noble metal can be avoided, and the preparation method is green and environment-friendly. The obtained compound contains imine, dichloromethylene and dibromomethylene structures, can be used as an important synthetic building block of active molecules, and has a wide application prospect in the field of biomedicine.)
技术领域
本发明涉及一种α,α-二氯或α,α-二溴取代的亚胺化合物及制备方法。
背景技术
氯元素和溴元素同属于卤素系列，具有相同的性质也表现出一定的差异，在自然界中常以化合态的形式存在。将二者的原子引入有机化合物分子中，其母体化合物的物理性质、化学性质和生物性质通常会发生显著的改变。凭借它们独特的性质特点，常用于医药、农药及其他精细化学品的合成。
氯原子可增加化合物分子的脂溶性、吸电子性的代谢阻碍作用及其位阻作用。α,α-二氯取代的亚胺化合物作为有机合成中间体，相比于在亚胺的邻位、亚甲基(-CH2-)的脱氢和羰基的胺化引入偕二氯亚甲基的方法，制备邻位含有偕二氯亚甲基的亚胺化合物的方法十分有限。Tetrahedron,1978,35,789-798报道过含二氯亚甲基取代的亚胺化合物的制备，但是该反应仅限于亚胺反应底物和需要较长的反应时间。同样，J.Org.Chem.2006,71,5881-5887也报道过类似底物的制备，但该反应需在催化剂下进行且适用范围窄。Org.Biomol.Chem.,2008,6,3667–3669报道过二氯丙烯取代的亚胺化合物的制备，该反应底物仅限于亚胺-戊烯反应底物，并且反应底物制备困难，反应能耗高。J.Org.Chem,2014,79,5558–5568报道过含三氟甲基二氯亚甲基取代的亚胺化合物的制备，该反应产物官能团转化不易，原料制备困难和氯化试剂所用量较高。
溴被称为“海洋元素”，与氟和氯相比，溴的电负性较低，溴容易以离子形式离去而成为亲电试剂，但存在于芳香环中较为稳定。α,α-二溴取代的亚胺化合物是一种重要的化工原料和有机合成砌块，已被用于构筑其它的功能性基团，但合成α,α-二溴取代的亚胺化合物的方法报道较少。J.Org.Chem.1991,56,4459-4463报道过二溴亚甲基取代的亚胺化合物的制备，该反应以四种氮杂1,3-二烯化合物为底物，反应较长的时间获得了衍生产品。Tetrahedron,1997,53,16313–16326发现含烯胺的氮杂环丙烷化合物碳碳双键上的氢被单溴替代时，过量的NBS会促进二溴产物的高产率生成，但并未进行深入的研究。Org.Lett.2017,19,6240-6243报道过含二溴亚甲基取代的亚胺化合物的制备，该反应仅以两种β-官能化烯胺为底物，且反应时间较长。
因此探索一种原料简单易得，转化率和反应收率高，官能团兼容性好，底物适用范围广，绿色环保的方法合成α,α-二氯和α,α-二溴取代的亚胺化合物具有显著的意义。
发明内容
本发明的目的旨在提供一种α,α-二氯或α,α-二溴取代的亚胺化合物及制备方法。
在本发明提供了一种α,α-二氯或α,α-二溴取代的亚胺化合物及制备方法，其包含下列步骤：
将如式A所示的化合物溶于有机溶剂中，再加入氯化试剂或溴化试剂，待反应完全后，经过滤、洗涤、分离等操作或其中部分操作得到如式B或C所对应的二氯或二溴乙酸酯取代的亚胺化合物。
其中如式A所示的化合物、如式B所示的化合物和如式C所示的化合物中，R1为芳香基团和杂芳香基团；R2为芳香基团和脂肪烷基；EWG吸电子基。
所述的氯化试剂为三氯均三嗪-2、4、6三酮(TCCA)、N-氯代丁二酰亚胺(NCS)和1,3-二氯-5,5-二甲基海因，溴化试剂为N-溴代丁二酰亚胺(NBS)、1,3-二溴-1,3,5-三嗪-2,4,6-三酮、1,3-二溴-5,5-二甲基海因和1,3,5-三溴-1,3,5-三嗪-2,4,6-三酮。
所述的如式A所示烯胺化合物与氯化试剂或溴化试剂的摩尔配比为1:2.5～3。
所述的溶剂为水，乙腈，乙醇，丙酮，四氢呋喃，乙酸乙酯，二氯甲烷，甲苯和四氯化碳。
所述的R1为芳香基团、杂芳香基团和脂肪烷基，其中芳香基团为苯基，4-甲基苯基，4-甲氧基苯基，4-氟苯基，4-氯苯基，4-溴苯基，4-碘苯基，4-三氟甲基苯基，4-硝基苯基，3-溴苯基，2-溴苯基，3-氯-4-氟-苯基，3,4-亚甲基二氧苯基，1-萘基和2-萘基；杂芳香基团为2-呋喃基，2-噻吩基和2-噻唑基；脂肪烷基为甲基。
所述的R2为芳香基团和脂肪烷基，其中芳香基团为苯基，4-甲基苯基，4-甲氧基苯基，4-氟苯基，4-氯苯基，4-三氟甲基苯基，3-甲氧基苯基，2-甲氧基苯基，1-萘基和2-萘基；其中脂肪烷基为烯丙基，炔丙基，异丙基，环丙基和4-硝基苄基。
所述的EWG吸电子基为氰基，甲基羰基，甲氧羰基，乙氧羰基，异丙氧羰基，叔丁氧羰基和苄氧羰基。
本发明的优点在于：
本发明得到了40中二氯取代的亚胺化合物和34中二溴取代的亚胺化合物，其中取代基包括芳香基、杂芳香基和脂肪基，说明本发明的合成方法对各种官能团的兼容性好、底物适用范围广，并且简单易得，转化率和反应收率高，绿色环保。
具体实施方式
下面通过具体实施例对本发明作进一步详述，以下实施例只是描述性的，不是限定性的，不能以此限定本发明的保护范围。
二氯取代的亚胺化合物的制备方法具体实施方式
通过下述实施例有助于进一步理解本发明，但并不因此将本发明限制在所述的实施例范围中。
实施例1
在一干燥的25mL反应瓶中，将A-1(59mg,0.20mmol)溶于乙腈(2mL)中，体系冷却至0℃后，一次性加入三氯均三嗪-2、4、6三酮(39mg,0.17mmol)，在0℃下继续搅拌反应1min。TLC检测反应完全后，向体系里加入乙酸乙酯(10mL)，然后用饱和碳酸氢钠(10mL)洗涤一次和饱和食盐水(10mL)洗涤三次，再用乙酸乙酯(10mL)萃取洗涤液三次，合并有机相，无水硫酸钠干燥，旋干后柱层析(淋洗液：石油醚/乙酸乙酯＝20/1to 10/1)即可得目标产物B-1(70mg,收率96％)为黄色油状液体。1H NMR(400MHz,CDCl3)δ7.41–7.28(m,5H),6.71–6.60(m,4H),4.42(q,J＝7Hz,2H),3.70(s,3H),1.38(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ165.07,163.39,157.54,140.23,132.40,129.67,129.60,128.30,123.45,113.86,85.33,64.25,55.40,14.13.
实施例2
在一干燥的25mL反应瓶中，将A-1(59mg,0.20mmol)溶于乙腈(2mL)中，体系冷却至0℃后，一次性加入N-氯代丁二酰亚胺(67mg,0.50mmol)，在0℃下继续搅拌反应3h。TLC检测反应完全后，向体系里加入乙酸乙酯(10mL)，然后用饱和碳酸氢钠(10mL)洗涤一次和饱和食盐水(10mL)洗涤三次，再用乙酸乙酯(10mL)萃取洗涤液三次，合并有机相，无水硫酸钠干燥，过滤旋干后柱层析(淋洗液：石油醚/乙酸乙酯＝20/1to 10/1)即可得目标产物B-1(66mg,收率90％)为黄色油状液体。1H NMR(400MHz,CDCl3)δ7.41–7.28(m,5H),6.71–6.60(m,4H),4.42(q,J＝7Hz,2H),3.70(s,3H),1.38(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ165.07,163.39,157.54,140.23,132.40,129.67,129.60,128.30,123.45,113.86,85.33,64.25,55.40,14.13.
实施例3
在一干燥的25mL反应瓶中，将A-1(59mg,0.20mmol)溶于乙腈(2mL)中，体系冷却至0℃后，一次性加入1,3-二氯-5,5-二甲基海因(49mg,0.25mmol)，在0℃下继续搅拌反应3h后，向体系里加入乙酸乙酯(10mL)，然后用饱和碳酸氢钠(10mL)洗涤一次和饱和食盐水(10mL)洗涤三次，再用乙酸乙酯(10mL)萃取洗涤液三次，合并有机相，无水硫酸钠干燥，过滤旋干后柱层析(淋洗液：石油醚/乙酸乙酯＝20/1to 10/1)即可得目标产物B-1(58mg,收率79％)为黄色油状液体。1H NMR(400MHz,CDCl3)δ7.41–7.28(m,5H),6.71–6.60(m,4H),4.42(q,J＝7Hz,2H),3.70(s,3H),1.38(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ165.07,163.39,157.54,140.23,132.40,129.67,129.60,128.30,123.45,113.86,85.33,64.25,55.40,14.13.
实施例4
与实验1类似的方法，A-1(59mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),水为溶剂，体系冷却至0℃反应3h,得到目标产物B-1(39mg,收率53％)为黄色油状液体。1H NMR(400MHz,CDCl3)δ7.41–7.28(m,5H),6.71–6.60(m,4H),4.42(q,J＝7Hz,2H),3.70(s,3H),1.38(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ165.07,163.39,157.54,140.23,132.40,129.67,129.60,128.30,123.45,113.86,85.33,64.25,55.40,14.13.
实施例5
与实验1类似的方法，A-1(59mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),丙酮为溶剂，体系冷却至0℃反应1min,得到目标产物B-1(57mg,收率78％)为黄色油状液体。1H NMR(400MHz,CDCl3)δ7.41–7.28(m,5H),6.71–6.60(m,4H),4.42(q,J＝7Hz,2H),3.70(s,3H),1.38(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ165.07,163.39,157.54,140.23,132.40,129.67,129.60,128.30,123.45,113.86,85.33,64.25,55.40,14.13.
实施例6
与实验1类似的方法，A-1(59mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),乙醇为溶剂，体系冷却至0℃反应3h,得到目标产物B-1(59mg,收率81％)为黄色油状液体。1H NMR(400MHz,CDCl3)δ7.41–7.28(m,5H),6.71–6.60(m,4H),4.42(q,J＝7Hz,2H),3.70(s,3H),1.38(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ165.07,163.39,157.54,140.23,132.40,129.67,129.60,128.30,123.45,113.86,85.33,64.25,55.40,14.13.
实施例7
与实验1类似的方法，A-1(59mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),四氢呋喃为溶剂，体系冷却至0℃反应1min,得到目标产物B-1(73mg,收率99％)为黄色油状液体。1H NMR(400MHz,CDCl3)δ7.41–7.28(m,5H),6.71–6.60(m,4H),4.42(q,J＝7Hz,2H),3.70(s,3H),1.38(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ165.07,163.39,157.54,140.23,132.40,129.67,129.60,128.30,123.45,113.86,85.33,64.25,55.40,14.13.
实施例8
与实验1类似的方法，A-1(59mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),乙酸乙酯为溶剂，体系冷却至0℃反应1min,得到目标产物B-1(68mg,收率93％)为黄色油状液体。1H NMR(400MHz,CDCl3)δ7.41–7.28(m,5H),6.71–6.60(m,4H),4.42(q,J＝7Hz,2H),3.70(s,3H),1.38(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ165.07,163.39,157.54,140.23,132.40,129.67,129.60,128.30,123.45,113.86,85.33,64.25,55.40,14.13.
实施例9
与实验1类似的方法，A-1(59mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),二氯甲烷为溶剂，体系冷却至0℃反应5min,得到目标产物B-1(64mg,收率87％)为黄色油状液体。1H NMR(400MHz,CDCl3)δ7.41–7.28(m,5H),6.71–6.60(m,4H),4.42(q,J＝7Hz,2H),3.70(s,3H),1.38(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ165.07,163.39,157.54,140.23,132.40,129.67,129.60,128.30,123.45,113.86,85.33,64.25,55.40,14.13.
实施例10
与实验1类似的方法，A-1(59mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),甲苯为溶剂，体系冷却至0℃反应10min,得到目标产物B-1(68mg,收率93％)为黄色油状液体。1H NMR(400MHz,CDCl3)δ7.41–7.28(m,5H),6.71–6.60(m,4H),4.42(q,J＝7Hz,2H),3.70(s,3H),1.38(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ165.07,163.39,157.54,140.23,132.40,129.67,129.60,128.30,123.45,113.86,85.33,64.25,55.40,14.13.
实施例11
与实验1类似的方法，A-1(59mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),四氯化碳为溶剂，体系冷却至0℃反应3h,得到目标产物B-1(59mg,收率80％)为黄色油状液体。1H NMR(400MHz,CDCl3)δ7.41–7.28(m,5H),6.71–6.60(m,4H),4.42(q,J＝7Hz,2H),3.70(s,3H),1.38(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ165.07,163.39,157.54,140.23,132.40,129.67,129.60,128.30,123.45,113.86,85.33,64.25,55.40,14.13.
实施例12
与实验1类似的方法，A-2(59mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),乙腈为溶剂，室温下反应12h,得到目标产物B-2(63mg,收率86％)为黄色油状液体。1H NMR(400MHz,CDCl3)δ7.36–7.24(m,5H),7.02(t,J＝8Hz,1H),6.55–6.47(m,1H),6.28–6.20(m,2H),4.41(q,J＝7Hz,2H),3.64(s,3H),1.36(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3,)δ165.21,164.84,159.84,148.94,131.87,129.66,129.58,129.44,128.06,113.16,110.80,106.35,84.81,64.37,55.30,14.10.
实施例13
与实验1类似的方法，A-3(59mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),乙腈为溶剂，室温下反应1.5h,得到目标产物B-3(65mg,收率89％)为黄色油状液体。1H NMR(400MHz,CDCl3)δ7.40–7.32(m,2H),7.28–7.19(m,3H),6.91(td,J＝8,2Hz,1H),6.75–6.66(m,2H),6.55(dd,J＝8,2Hz,1H),4.35(q,J＝7Hz,2H),3.69(s,3H),1.32(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ166.53,164.86,149.03,137.82,132.61,129.54,128.80,127.70,125.58,120.56,120.50,111.70,84.55,64.28,55.55,13.99.
实施例14
与实验1类似的方法，A-4(53mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),乙腈为溶剂，室温下反应5h,得到目标产物B-4(65mg,收率97％)为浅黄色固体。1HNMR(400MHz,CDCl3)δ7.35–7.21(m,5H),7.15–7.06(m,2H),6.98–6.89(m,1H),6.71–6.59(m,2H),4.39(q,J＝7Hz,2H),1.35(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ165.09,164.76,147.66,131.76,129.57,128.56,127.99,124.86,120.59,84.80,64.27,14.03.
实施例15
与实验1类似的方法，A-5(57mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),乙腈为溶剂，室温下反应5h,得到目标产物B-5(65mg,收率92％)为浅黄色固体。1HNMR(400MHz,CDCl3)δ7.37–7.27(m,5H),6.87–6.77(m,2H),6.69–6.59(m,2H),4.41(q,J＝7Hz,2H),1.37(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ165.48,164.81,160.27(d,J＝243Hz),143.61(d,J＝3Hz),131.77,129.80,129.59,128.25,122.68(d,J＝8Hz),115.50(d,J＝23Hz),84.85,64.37,14.10.19F NMR(376MHz,CDCl3)δ-117.79.
实施例16
与实验1类似的方法，A-6(60mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),乙腈为溶剂，室温下反应12h,得到目标产物B-6(50mg,收率68％)为黄色油状液体。1H NMR(400MHz,CDCl3)δ7.37–7.27(m,5H),7.14–7.04(m,2H),6.64–6.57(m,2H),4.41(q,J＝7Hz,2H),1.36(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ165.91,164.73,146.21,131.58,130.52,129.89,129.55,128.82,128.25,122.18,84.69,64.42,14.09.
实施例17
与实验1类似的方法，A-7(67mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),乙腈为溶剂，室温下反应h,得到目标产物B-7(80mg,收率99％)为浅黄色油状液体。1H NMR(400MHz,CDCl3)δ7.40(d,J＝8Hz,2H),7.36–7.26(m,5H),6.75(d,J＝8Hz,2H),4.41(q,J＝7Hz,2H),1.36(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ166.65,164.59,150.92,131.26,130.05,129.47,128.25,126.80(q,J＝32Hz),125.98(q,J＝4Hz),124.16(q,J＝270Hz),120.42,84.41,64.52,14.08.19F NMR(376MHz,CDCl3)δ-62.18.
实施例18
与实验1类似的方法，A-8(63mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),乙腈为溶剂，室温下反应h,得到目标产物B-8(76mg,收率99％)为黄色油状液体。1H NMR(400MHz,CDCl3)δ8.00–7.90(m,1H),7.79–7.72(m,1H),7.57–7.43(m,3H),7.32–7.25(m,2H),7.25–7.19(m,1H),7.19–7.09(m,3H),6.45(d,J＝7Hz,1H),4.46(q,J＝7Hz,2H),1.40(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ166.05,165.03,144.30,133.71,131.68,129.72,129.01,127.99,127.95,127.11,126.44,126.07,125.42,124.94,123.56,114.28,84.82,64.58,14.09.
实施例19
与实验1类似的方法，A-9(65mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),乙腈为溶剂，室温下反应1min,得到目标产物B-9(77mg,收率98％)为无色油状液体。1H NMR(400MHz,CDCl3)δ8.21–8.12(m,2H),7.52–7.45(m,3H),7.40–7.30(m,4H),4.49(s,2H),4.38(q,J＝7Hz,2H),1.33(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ167.94,164.89,147.14,146.29,131.28,130.08,128.72,128.70,128.06,123.76,84.77,64.38,56.21,14.08.
实施例20
与实验1类似的方法，A-10(46mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),乙腈为溶剂，室温下反应h,得到目标产物B-10(59mg,收率99％)为无色油状液体。1H NMR(400MHz,CDCl3)δ7.46(s,5H),4.33(q,J＝7Hz,2H),2.65–2.53(m,1H),1.32(t,J＝7Hz,3H),0.92–0.85(m,2H),0.85–0.77(m,2H).13C NMR(100MHz,CDCl3)δ165.14,162.79,132.18,129.47,129.44,128.34,85.13,63.93,35.23,14.04,10.26.
实施例21
与实验1类似的方法，A-11(62mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),乙腈为溶剂，室温下反应1min,得到目标产物B-11(70mg,收率92％)为黄色油状液体。1H NMR(400MHz,CDCl3)δ7.23(d,J＝8Hz,2H),7.12(d,J＝8Hz,2H),6.72–6.60(m,4H),4.41(q,J＝7Hz,2H),3.71(s,3H),2.33(s,3H),1.38(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ165.15,163.60,157.44,140.43,139.69,129.56,129.32,129.02,123.40,113.85,85.50,64.20,55.41,21.54,14.13.
实施例22
与实验1类似的方法，A-12(65mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),乙腈为溶剂，室温下反应5min,得到目标产物B-12(71mg,收率90％)为黄色油状液体。1H NMR(400MHz,CDCl3)δ7.31–7.26(m,2H),6.86–6.78(m,2H),6.72–6.62(m,4H),4.40(q,J＝7Hz,2H),3.79(s,3H),3.72(s,3H),1.37(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ165.17,163.28,160.41,157.42,140.57,131.20,124.34,123.37,113.93,113.75,85.68,64.18,55.42,55.31,14.13.
实施例23
与实验1类似的方法，A-13(63mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),乙腈为溶剂，室温下反应h,得到目标产物B-13(69mg,收率90％)为黄色油状液体。1H NMR(400MHz,CDCl3)δ7.39–7.30(m,2H),7.06–6.97(m,2H),6.72–6.65(m,2H),6.65–6.59(m,2H),4.42(q,J＝7Hz,2H),3.72(s,3H),1.38(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ164.93,163.22(d,J＝249Hz),162.54,157.65,140.09,131.82(d,J＝8Hz),128.27(d,J＝4Hz),123.31,115.61(d,J＝22Hz),113.99,85.28,64.32,55.43,14.14.19F NMR(376MHz,CDCl3)δ-110.11.
实施例24
与实验1类似的方法，A-14(66mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),乙腈为溶剂，室温下反应h,得到目标产物B-14(73mg,收率91％)为黄色油状液体。1H NMR(400MHz,CDCl3)δ7.33–7.26(m,4H),6.71–6.66(m,2H),6.66–6.59(m,2H),4.42(q,J＝7Hz,2H),3.72(s,3H),1.38(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ164.85,162.33,157.71,139.93,135.86,131.12,130.70,128.71,123.31,114.03,85.10,64.36,55.44,14.14.
实施例25
与实验1类似的方法，A-15(73mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),乙腈为溶剂，室温下反应1.5h,得到目标产物B-15(78mg,收率90％)为黄色油状液体。1H NMR(400MHz,CDCl3)δ(ppm):7.60(d,J＝8Hz,2H),7.49(d,J＝8Hz,2H),6.71–6.64(m,2H),6.64–6.58(m,2H),4.44(q,J＝7Hz,2H),3.72(s,3H),1.40(t,J＝7Hz,3H)；13C NMR(100MHz,CDCl3)δ(ppm):164.72,161.94,157.86,139.63,136.05,131.58(q,J＝32Hz),130.27,125.31(q,J＝4Hz),123.78(q,J＝270Hz),123.31,114.09,84.85,64.46,55.44,14.14；19F NMR(376MHz,CDCl3)δ(ppm):-62.94.
实施例26
与实验1类似的方法，A-16(75mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),乙腈为溶剂，室温下反应2h,得到目标产物B-16(83mg,收率93％)为黄色油状液体。1H NMR(400MHz,CDCl3)δ7.36–7.30(m,2H),7.27–7.19(m,3H),6.92(td,J＝8,2Hz,1H),6.76–6.67(m,2H),6.55(dd,J＝8,2Hz,1H),4.40(q,J＝7Hz,2H),3.68(s,3H),1.36(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ166.55,164.89,149.04,137.80,132.61,129.56,128.82,127.72,125.60,120.59,120.50,111.66,84.55,64.32,55.56,14.02.
实施例27
与实验1类似的方法，A-17(75mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),乙腈为溶剂，室温下反应1min,得到目标产物B-17(75mg,收率84％)为黄色油状液体。1H NMR(400MHz,CDCl3)δ7.54(s,1H),7.50(d,J＝8Hz,1H),7.27–7.22(m,1H),7.19(t,J＝8Hz,1H),6.72–6.66(m,2H),6.66–6.61(m,2H),4.43(q,J＝7Hz,2H),3.72(s,3H),1.39(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ164.79,161.50,157.83,139.71,134.29,132.78,132.32,129.88,128.47,123.42,122.42,114.05,84.99,64.39,55.45,14.14.
实施例28
与实验1类似的方法，A-18(75mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),乙腈为溶剂，室温下反应12h,得到目标产物B-18(73mg,收率82％)为黄色油状液体。.1H NMR(400MHz,CDCl3)δ7.67(dd,J＝8,2Hz,1H),7.51(dd,J＝8,1Hz,1H),7.39(td,J＝8,1Hz,1H),7.26(td,J＝8,2Hz,1H),6.75–6.69(m,2H),6.69–6.64(m,2H),4.57–4.36(m,2H),3.71(s,3H),1.42(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ164.95,160.85,158.13,139.63,134.30,133.33,131.24,131.06,127.01,123.67,122.30,113.77,84.90,64.27,55.39,14.21.
实施例29
与实验1类似的方法，A-19(70mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),乙腈为溶剂，室温下反应12h,得到目标产物B-19(83mg,收率99％)为黄色油状液体。1H NMR(400MHz,CDCl3)δ7.47(dd,J＝7,2Hz,1H),7.23–7.16(m,1H),7.09(t,J＝9Hz,1H),6.73–6.67(m,2H),6.65–6.60(m,2H),4.43(q,J＝7Hz,2H),3.73(s,3H),1.39(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ164.68,160.94,158.68(d,J＝252Hz),157.88,139.61,131.98,130.05(d,J＝8Hz),129.25(d,J＝5Hz),123.29,121.51(d,J＝18Hz),116.79(d,J＝21Hz),114.14,84.98,64.45,55.46,14.15.19F NMR(376MHz,CDCl3)δ-112.32.
实施例30
与实验1类似的方法，A-20(68mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),乙腈为溶剂，室温下反应1h,得到目标产物B-20(63mg,收率77％)为浅黄色油状液体。1H NMR(400MHz,CDCl3)δ6.86–6.79(m,2H),6.74(d,J＝8Hz,1H),6.72–6.64(m,4H),5.97(s,2H),4.41(q,J＝7Hz,2H),3.73(s,3H),1.38(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ165.07,162.79,157.56,148.64,147.60,140.30,125.59,124.07,123.36,113.97,110.07,108.34,101.54,85.52,64.23,55.44,14.14.
实施例31
与实验1类似的方法，A-21(61mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),乙腈为溶剂，室温下反应5h,得到目标产物B-21(61mg,收率82％)为黄色油状液体。1H NMR(400MHz,CDCl3)δ7.40(d,J＝5Hz 1H),7.30(d,J＝4Hz,1H),6.98–6.93(m,1H),6.80–6.74(m,2H),6.74–6.69(m,2H),4.39(q,J＝7Hz,2H),3.76(s,3H),1.33(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ164.72,157.69,156.59,141.05,132.31,130.27,129.75,126.60,122.10,114.31,85.63,64.31,55.49,14.02.
实施例32
与实验1类似的方法，A-22(72mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),乙腈为溶剂，室温下反应2min,得到目标产物B-22(82mg,收率96％)为黄色油状液体。1H NMR(400MHz,CDCl3)δ7.48–7.41(m,2H),7.41–7.35(m,3H),7.36–7.27(m,5H),6.67–6.59(m,2H),6.56–6.48(m,2H),5.40(s,2H),3.70(s,3H).13C NMR(100MHz,CDCl3)δ165.03,163.25,157.55,140.01,134.88,132.24,129.61,129.60,128.74,128.67,128.60,128.29,123.53,113.76,85.40,69.56,55.36.
实施例33
与实验1类似的方法，A-23(66mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),乙腈为溶剂，室温下反应2h,得到目标产物B-23(75mg,收率94％)为黄色油状液体。1H NMR(400MHz,CDCl3)δ8.13–8.05(m,2H),7.62–7.54(m,1H),7.52–7.43(m,4H),7.43–7.33(m,3H),6.64–6.55(m,2H),6.42–6.34(m,2H),3.67(s,3H).13C NMR(100MHz,CDCl3)δ185.62,164.61,157.66,140.05,132.99,132.77,132.02,130.91,130.03,129.47,128.63,128.29,123.08,113.94,89.40,55.38.
实施例34
与实验1类似的方法，A-24(50mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),乙腈为溶剂，室温下反应5min,得到目标产物B-24(59mg,收率93％)为黄色油状液体。1H NMR(400MHz,CDCl3)δ7.48–7.30(m,5H),6.81–6.75(m,2H),6.72–6.66(m,2H),3.73(s,3H).13C NMR(100MHz,CDCl3)δ158.79,158.53,138.87,130.62,130.33,129.89,128.76,124.57,114.32,114.04,71.65,55.46.
实施例35
与实验1类似的方法，A-25(53mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),乙腈为溶剂，室温下反应2min,得到目标产物B-25(62mg,收率92％)为黄色油状液体。1H NMR(400MHz,CDCl3)δ8.06–7.97(m,2H),7.59–7.51(m,1H),7.48–7.41(m,2H),6.87–6.81(m,2H),6.66–6.59(m,2H),3.77(s,3H),2.27(s,3H).13C NMR(100MHz,CDCl3)δ186.14,165.85,157.21,141.17,133.26,132.50,130.97,128.18,120.53,114.38,90.27,55.53,15.36.
实施例36
与实验1类似的方法，A-26(47mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),乙腈为溶剂，室温下反应50min,得到目标产物B-26(58mg,收率94％)为浅黄色油状液体。1H NMR(400MHz,CDCl3)δ8.10–8.03(m,2H),7.60–7.54(m,1H),7.50–7.44(m,2H),7.35–7.28(m,2H),7.14–7.07(m,1H),6.69–6.63(m,2H),2.23(s,3H).13C NMR(100MHz,CDCl3)δ185.98,166.24,148.35,133.42,132.35,131.01,129.18,128.25,124.86,118.52,89.93,15.55.
实施例37
与实验1类似的方法，A-27(54mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),乙腈为溶剂，室温下反应1.5h,得到目标产物B-27(66mg,收率97％)为黄色油状液体。1H NMR(400MHz,CDCl3)δ8.07–8.00(m,2H),7.60–7.53(m,1H),7.49–7.43(m,2H),7.29–7.25(m,2H),6.62–6.56(m,2H),2.21(s,3H).13C NMR(100MHz,CDCl3)δ185.85,166.98,146.80,133.53,132.22,130.95,130.35,129.33,128.31,120.03,89.60,15.73.
实施例38
与实验1类似的方法，A-28(40mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),乙腈为溶剂，室温下反应1min,得到目标产物B-28(46mg,收率85％)为无色油状液体。1H NMR(400MHz,CDCl3)δ7.87–7.78(m,2H),7.51–7.46(m,1H),7.40–7.34(m,2H),2.96–2.89(m,1H),2.36(s,3H),0.85–0.80(m,2H),0.61–0.53(m,2H).13C NMR(100MHz,CDCl3)δ187.29,162.23,133.38,132.68,130.87,127.82,91.24,33.59,13.53,9.27.
实施例39
与实验1类似的方法，A-29(47mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),乙腈为溶剂，室温下反应1min,得到目标产物B-29(54mg,收率88％)为浅黄色油状液体。1H NMR(400MHz,CDCl3)δ6.90–6.84(m,2H),6.76–6.67(m,2H),4.37(q,J＝7Hz,2H),3.78(s,3H),2.17(s,3H),1.33(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ164.65,164.22,157.08,141.26,120.80,114.31,85.72,64.11,55.51,14.44,14.01.
实施例40
与实验1类似的方法，A-30(41mg,0.20mmol),三氯均三嗪-2、4、6三酮(39mg,0.17mmol),乙腈为溶剂，室温下反应1.5h,得到目标产物B-30(37mg,收率67％)为浅黄色油状液体。1H NMR(400MHz,CDCl3)δ6.90–6.86(m,2H),6.74–6.69(m,2H),3.79(s,3H),2.50(s,3H),2.22(s,3H).13C NMR(100MHz,CDCl3)δ193.40,165.82,157.33,140.91,120.97,114.42,90.48,55.59,26.10,14.77.
二溴取代的亚胺化合物的制备方法具体实施流程：
实施例1
在一干燥的25mL反应瓶中，将A-1(59mg,0.20mmol)溶于乙腈(2mL)中，体系冷却至0℃后，一次性加入N-溴代丁二酰亚胺(89mg,0.50mmol)，在0℃下继续搅拌反应3h。TLC检测反应完全后,反应液旋干后柱层析((淋洗液：石油醚/乙酸乙酯＝20/1to 10/1)即可得目标产物C-1(86mg,收率94％)为亮黄色油状液体。1H NMR(400MHz,CDCl3)δ7.43–7.36(m,2H),7.36–7.27(m,3H),6.69–6.60(m,4H),4.37(q,J＝7Hz,2H),3.70(s,3H),1.33(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ165.03,163.75,157.43,140.52,133.09,129.86,129.51,128.20,123.32,113.83,64.44,62.41,55.40,14.04.
实施例2
在一干燥的25mL反应瓶中，将A-1(59mg,0.20mmol)溶于乙腈(2mL)中，体系冷却至0℃后，一次性加入1,3-二溴-1,3,5-三嗪-2,4,6-三酮(143mg,0.50mmol)，在0℃下继续搅拌反应3h。TLC检测反应完全后,反应液旋干后柱层析((淋洗液：石油醚/乙酸乙酯＝20/1to10/1)即可得目标产物C-1(58mg,收率64％)为亮黄色油状液体。1H NMR(400MHz,CDCl3)δ(ppm):7.43–7.36(m,2H),7.36–7.27(m,3H),6.69–6.60(m,4H),4.37(q,J＝7Hz,2H),3.70(s,3H),1.33(t,J＝7Hz,3H)；13C NMR(100MHz,CDCl3)δ(ppm):165.03,163.75,157.43,140.51,133.01,129.86,129.51,128.20,123.32,113.83,64.44,62.41,55.40,14.04.
实施例3
在一干燥的25mL反应瓶中，将A-1(59mg,0.20mmol)溶于乙腈(2mL)中，体系冷却至0℃后，一次性加入1,3-二溴-5,5-二甲基海因(143mg,0.50mmol)，在0℃下继续搅拌反应3h。TLC检测反应完全后,反应液旋干后柱层析((淋洗液：石油醚/乙酸乙酯＝20/1to 10/1)即可得目标产物C-1(41mg,收率45％)为亮黄色油状液体。1H NMR(400MHz,CDCl3)δ(ppm):7.43–7.36(m,2H),7.36–7.27(m,3H),6.69–6.60(m,4H),4.37(q,J＝7Hz,2H),3.70(s,3H),1.33(t,J＝7Hz,3H)；13C NMR(100MHz,CDCl3)δ(ppm):165.03,163.75,157.43,140.51,133.01,129.86,129.51,128.20,123.32,113.83,64.44,62.41,55.40,14.04.
实施例4
在一干燥的25mL反应瓶中，将A-1(59mg,0.20mmol)溶于乙腈(2mL)中，体系冷却至0℃后，一次性加入1,3,5-三溴-1,3,5-三嗪-2,4,6-三酮(61mg,0.17mmol)，在0℃下继续搅拌反应3h。TLC检测反应完全后,反应液旋干后柱层析((淋洗液：石油醚/乙酸乙酯＝20/1to10/1)即可得目标产物C-1(5mg,收率5％)为亮黄色油状液体。1H NMR(400MHz,CDCl3)δ(ppm):7.43–7.36(m,2H),7.36–7.27(m,3H),6.69–6.60(m,4H),4.37(q,J＝7Hz,2H),3.70(s,3H),1.33(t,J＝7Hz,3H)；13C NMR(100MHz,CDCl3)δ(ppm):165.03,163.75,157.43,140.51,133.01,129.86,129.51,128.20,123.32,113.83,64.44,62.41,55.40,14.04.
实施例5
与实验1类似的方法，A-1(59mg,0.20mmol),N-溴代丁二酰亚胺(89mg,0.50mmol),乙醇为溶剂，0℃下反应3h,得到目标产物C-1(83mg,收率91％)为亮黄色油状液体。1H NMR(400MHz,CDCl3)δ7.43–7.36(m,2H),7.36–7.27(m,3H),6.69–6.60(m,4H),4.37(q,J＝7Hz,2H),3.70(s,3H),1.33(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ165.03,163.75,157.43,140.52,133.09,129.86,129.51,128.20,123.32,113.83,64.44,62.41,55.40,14.04.
实施例6
与实验1类似的方法，A-1(59mg,0.20mmol),N-溴代丁二酰亚胺(89mg,0.50mmol),丙酮为溶剂，0℃下反应3h,得到目标产物C-1(80mg,收率88％)为亮黄色油状液体。1H NMR(400MHz,CDCl3)δ7.43–7.36(m,2H),7.36–7.27(m,3H),6.69–6.60(m,4H),4.37(q,J＝7Hz,2H),3.70(s,3H),1.33(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ165.03,163.75,157.43,140.52,133.09,129.86,129.51,128.20,123.32,113.83,64.44,62.41,55.40,14.04.
实施例7
与实验1类似的方法，A-1(59mg,0.20mmol),N-溴代丁二酰亚胺(89mg,0.50mmol),四氢呋喃为溶剂，0℃下反应3h,得到目标产物C-1(56mg,收率62％)为亮黄色油状液体。1HNMR(400MHz,CDCl3)δ7.43–7.36(m,2H),7.36–7.27(m,3H),6.69–6.60(m,4H),4.37(q,J＝7Hz,2H),3.70(s,3H),1.33(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ165.03,163.75,157.43,140.52,133.09,129.86,129.51,128.20,123.32,113.83,64.44,62.41,55.40,14.04.
实施例8
与实验1类似的方法，A-1(59mg,0.20mmol),N-溴代丁二酰亚胺(89mg,0.50mmol),乙酸乙酯为溶剂，0℃下反应3h,得到目标产物C-1(82mg,收率90％)为亮黄色油状液体。1HNMR(400MHz,CDCl3)δ7.43–7.36(m,2H),7.36–7.27(m,3H),6.69–6.60(m,4H),4.37(q,J＝7Hz,2H),3.70(s,3H),1.33(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ165.03,163.75,157.43,140.52,133.09,129.86,129.51,128.20,123.32,113.83,64.44,62.41,55.40,14.04.
实施例9
与实验1类似的方法，A-1(59mg,0.20mmol),N-溴代丁二酰亚胺(89mg,0.50mmol),二氯甲烷为溶剂，0℃下反应3h,得到目标产物C-1(82mg,收率90％)为亮黄色油状液体。1HNMR(400MHz,CDCl3)δ7.43–7.36(m,2H),7.36–7.27(m,3H),6.69–6.60(m,4H),4.37(q,J＝7Hz,2H),3.70(s,3H),1.33(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ165.03,163.75,157.43,140.52,133.09,129.86,129.51,128.20,123.32,113.83,64.44,62.41,55.40,14.04.
实施例10
与实验1类似的方法，A-1(59mg,0.20mmol),N-溴代丁二酰亚胺(89mg,0.50mmol),甲苯为溶剂，0℃下反应3h,得到目标产物C-1(43mg,收率47％)为亮黄色油状液体。1H NMR(400MHz,CDCl3)δ7.43–7.36(m,2H),7.36–7.27(m,3H),6.69–6.60(m,4H),4.37(q,J＝7Hz,2H),3.70(s,3H),1.33(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ165.03,163.75,157.43,140.52,133.09,129.86,129.51,128.20,123.32,113.83,64.44,62.41,55.40,14.04.
实施例11
与实验1类似的方法，A-1(59mg,0.20mmol),N-溴代丁二酰亚胺(89mg,0.50mmol),四氯化碳为溶剂，0℃下反应5min,得到目标产物C-1(81mg,收率89％)为亮黄色油状液体。1H NMR(400MHz,CDCl3)δ7.43–7.36(m,2H),7.36–7.27(m,3H),6.69–6.60(m,4H),4.37(q,J＝7Hz,2H),3.70(s,3H),1.33(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ165.03,163.75,157.43,140.52,133.09,129.86,129.51,128.20,123.32,113.83,64.44,62.41,55.40,14.04.
实施例12
与实验1类似的方法，A-2(59mg,0.20mmol),N-溴代丁二酰亚胺(89mg,0.50mmol),乙腈为溶剂，室温下反应5min,得到目标产物C-2(79mg,收率87％)为亮黄色油状液体。1HNMR(400MHz,CDCl3)δ7.41–7.32(m,2H),7.28–7.17(m,3H),6.91(td,J＝8,2Hz,1H),6.76–6.63(m,2H),6.55(dd,J＝8,2Hz,1H),4.35(q,J＝7Hz,2H),3.69(s,3H),1.32(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ166.87,164.91,149.09,138.11,133.31,129.46,128.97,127.64,125.49,120.52,120.48,111.70,64.49,61.34,55.60,13.92.
实施例13
与实验1类似的方法，A-3(53mg,0.20mmol),N-溴代丁二酰亚胺(89mg,0.50mmol),乙腈为溶剂，室温下反应1h,得到目标产物C-3(78mg,收率92％)为浅黄色固体。1H NMR(400MHz,CDCl3)δ7.40–7.32(m,2H),7.30–7.23(m,3H),7.18–7.07(m,2H),6.95(td,J＝7,1Hz,1H),6.72–6.60(m,2H),4.37(q,J＝7Hz,2H),1.33(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ165.46,164.89,148.03,132.56,129.87,129.54,128.59,127.97,124.79,120.61,64.56,61.78,14.02.
实施例14
与实验1类似的方法，A-4(57mg,0.20mmol),N-溴代丁二酰亚胺(89mg,0.50mmol),乙腈为溶剂，室温下反应30min,得到目标产物C-4(76mg,收率86％)为浅黄色固体。1H NMR(400MHz,CDCl3)δ7.38–7.26(m,5H),6.87–6.77(m,2H),6.69–6.59(m,2H),4.37(q,J＝7Hz,2H),1.33(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ165.80,164.82,160.19(d,J＝243Hz),143.93(d,J＝3Hz),132.48,129.80,129.70,128.16,122.55(d,J＝8Hz),115.46(d,J＝23Hz),64.56,61.72,14.01.19F NMR(376MHz,CDCl3)δ-118.03.
实施例15
与实验1类似的方法，A-5(65mg,0.20mmol),N-溴代丁二酰亚胺(89mg,0.50mmol),乙腈为溶剂，室温下反应1min,得到目标产物C-5(86mg,收率89％)为无色油状液体。1H NMR(400MHz,CDCl3)δ8.22–8.12(m,2H),7.52–7.44(m,3H),7.43–7.35(m,4H),4.49(s,2H),4.35(q,J＝7Hz,2H),1.31(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ168.13,164.86,147.10,146.49,131.98,129.97,129.04,128.60,128.06,123.76,64.59,61.62,56.53,14.01.
实施例16
与实验1类似的方法，A-6(67mg,0.20mmol),N-溴代丁二酰亚胺(89mg,0.50mmol),乙腈为溶剂，室温下反应1min,得到目标产物C-6(95mg,收率96％)为黄色油状液体。1H NMR(400MHz,CDCl3)δ7.39(d,J＝8.4Hz,2H),7.35–7.24(m,5H),6.75(d,J＝8Hz,2H),4.37(q,J＝7Hz,2H),1.32(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ166.89,164.64,151.21,131.94,129.93,129.66,128.16,126.62(q,J＝32Hz),125.92(q,J＝4Hz),124.19(q,J＝270Hz),120.33,64.70,61.06,13.97.19F NMR(376MHz,CDCl3)δ-62.14.
实施例17
与实验1类似的方法，A-7(46mg,0.20mmol),N-溴代丁二酰亚胺(89mg,0.50mmol),乙腈为溶剂，室温下反应0.5h,得到目标产物C-7(75mg,收率96％)为无色油状液体。1H NMR(400MHz,CDCl3)δ7.54–7.48(m,2H),7.48–7.41(m,3H),4.30(q,J＝7Hz,2H),2.59–2.50(m,1H),1.30(t,J＝7Hz,3H),0.91–0.86(m,2H),0.85–0.77(m,2H).13C NMR(100MHz,CDCl3)δ164.97,163.07,132.89,129.68,129.30,128.17,64.09,62.02,35.52,13.95,10.31.
实施例18
与实验1类似的方法，A-8(62mg,0.20mmol),N-溴代丁二酰亚胺(89mg,0.50mmol),乙腈为溶剂，室温下反应1min,得到目标产物C-8(89mg,收率95％)为亮黄色油状液体。1HNMR(400MHz,CDCl3)δ7.27(d,J＝8Hz,2H),7.10(d,J＝8Hz,2H),6.70–6.61(m,4H),4.37(q,J＝7Hz,2H),3.71(s,3H),2.32(s,3H),1.33(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ165.10,163.95,157.34,140.72,139.57,130.02,129.76,128.91,123.28,113.83,64.39,62.75,55.40,21.52,14.04.
实施例19
与实验1类似的方法，A-9(65mg,0.20mmol),N-溴代丁二酰亚胺(89mg,0.50mmol),乙腈为溶剂，室温下反应3min,得到目标产物C-9(89mg,收率92％)为亮黄色油状液体。1HNMR(400MHz,CDCl3)δ7.36–7.28(m,2H),6.85–6.77(m,2H),6.71–6.60(m,4H),4.36(q,J＝7Hz,2H),3.79(s,3H),3.72(s,3H),1.33(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ165.14,163.60,160.30,157.30,140.86,131.37,125.07,123.30,113.90,113.63,64.38,55.42,55.32,14.06.
实施例20
与实验1类似的方法，A-10(63mg,0.20mmol),N-溴代丁二酰亚胺(89mg,0.50mmol),乙腈为溶剂，室温下反应0.5h,得到目标产物C-10(84mg,收率89％)为亮黄色油状液体。1H NMR(400MHz,CDCl3)δ7.42–7.35(m,2H),7.04–6.96(m,2H),6.71–6.65(m,2H),6.65–6.58(m,2H),4.38(q,J＝7Hz,2H),3.72(s,3H),1.35(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ164.92,163.13(d,J＝249Hz),162.94,157.55,140.38,132.01(d,J＝8Hz),129.00(d,J＝4Hz),123.18,115.49(d,J＝22Hz),113.96,64.52,62.29,55.43,14.06.19F NMR(376MHz,CDCl3)δ-110.25.
实施例21
与实验1类似的方法，A-11(66mg,0.20mmol),N-溴代丁二酰亚胺(89mg,0.50mmol),乙腈为溶剂，室温下反应1h,得到目标产物C-11(84mg,收率86％)为亮黄色油状液体。1H NMR(400MHz,CDCl3)δ7.37–7.31(m,2H),7.31–7.26(m,2H),6.71–6.65(m,2H),6.65–6.58(m,2H),4.39(q,J＝7Hz,2H),3.72(s,3H),1.35(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ164.85,162.73,157.60,140.22,135.72,131.44,131.32,128.59,123.17,114.00,64.55,61.97,55.43,14.06.
实施例22
与实验1类似的方法，A-12(75mg,0.20mmol),N-溴代丁二酰亚胺(89mg,0.50mmol),乙腈为溶剂，室温下反应1min,得到目标产物C-12(95mg,收率89％)为亮黄色油状液体。1H NMR(400MHz,CDCl3)δ7.48–7.39(m,2H),7.30–7.23(m,2H),6.71–6.64(m,2H),6.64–6.57(m,2H),4.38(q,J＝7Hz,2H),3.72(s,3H),1.35(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ164.84,162.73,157.63,140.20,131.93,131.54,124.08,123.18,114.03,64.57,61.90,55.45,14.08.
实施例23
与实验1类似的方法，A-13(75mg,0.20mmol),N-溴代丁二酰亚胺(89mg,0.50mmol),乙腈为溶剂，室温下反应1min,得到目标产物C-13(94mg,收率88％)为黄色油状液体。1H NMR(400MHz,CDCl3)δ7.59(t,J＝2Hz,1H),7.51–7.44(m,1H),7.29(dt,J＝8,1Hz,1H),7.18(t,J＝8Hz,1H),6.71–6.66(m,2H),6.66–6.60(m,2H),4.39(q,J＝7Hz,2H),3.71(s,3H),1.35(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ164.76,161.88,157.71,139.99,134.99,132.65,132.51,129.75,128.69,123.25,122.28,114.01,64.57,61.76,55.44,14.06.
实施例24
与实验1类似的方法，A-14(75mg,0.20mmol),N-溴代丁二酰亚胺(89mg,0.50mmol),乙腈为溶剂，室温下反应5min,得到目标产物C-14(91mg,收率85％)为亮黄色油状液体。1H NMR(400MHz,CDCl3)δ7.84(dd,J＝8,2Hz,1H),7.50(dd,J＝8,1Hz,1H),7.40(td,J＝8,1Hz,1H),7.26(td,J＝8,2Hz 1H),6.73–6.68(m,2H),6.68–6.64(m,2H),4.55–4.33(m,2H),3.71(s,3H),1.40(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ165.01,161.37,158.05,139.78,135.14,133.34,131.21,131.01,127.00,123.58,122.29,113.71,64.46,61.28,55.39,14.17.
实施例25
与实验1类似的方法，A-15(70mg,0.20mmol),N-溴代丁二酰亚胺(89mg,0.50mmol),乙腈为溶剂，室温下反应1min,得到目标产物C-15(90mg,收率89％)为亮黄色油状液体。1H NMR(400MHz,CDCl3)δ7.52(dd,J＝7,2Hz,1H),7.27–7.23(m,1H),7.08(t,J＝9Hz,1H),6.70(d,J＝9Hz,2H),6.62(d,J＝9Hz,2H),4.40(q,J＝7Hz,2H),3.73(s,3H),1.37(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ164.71,161.38,158.58(d,J＝252Hz),157.77,139.91,132.19,130.28(d,J＝8Hz),130.01(d,J＝4Hz),123.14,121.35(d,J＝18Hz),116.65(d,J＝21Hz),114.11,64.65,61.73,55.46,14.08.19F NMR(376MHz,CDCl3)δ-112.48.
实施例26
与实验1类似的方法，A-16(68mg,0.20mmol),N-溴代丁二酰亚胺(89mg,0.50mmol),乙腈为溶剂，室温下反应1min,得到目标产物C-16(88mg,收率88％)为黄色油状液体。1H NMR(400MHz,CDCl3)δ6.91–6.83(m,2H),6.75–6.71(m,1H),6.71–6.63(m,4H),5.96(s,2H),4.38(q,J＝7Hz,2H),3.73(s,3H),1.35(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ165.03,163.15,157.46,148.52,147.49,140.58,126.33,124.19,123.22,113.94,110.31,108.21,101.51,64.42,62.70,55.43,14.06.
实施例27
与实验1类似的方法，A-19(72mg,0.20mmol)，N-溴代丁二酰亚胺(89mg,0.50mmol),乙腈为溶剂，室温下反应1min,得到目标产物C-19(100mg,收率97％)为浅黄色固体。1H NMR(400MHz,CDCl3)δ7.46–7.41(m,2H),7.40–7.34(m,5H),7.34–7.26(m,3H),6.66–6.60(m,2H),6.56–6.48(m,2H),5.37(s,2H),3.70(s,3H).13C NMR(100MHz,CDCl3)δ164.95,163.65,157.45,140.28,134.90,132.97,129.82,129.50,128.72,128.63,128.54,128.18,123.41,113.74,69.77,62.21,55.37.
实施例28
与实验1类似的方法，A-18(66mg,0.6mmol),N-溴代丁二酰亚胺(89mg,0.50mmol),乙腈为溶剂，室温下反应5h,得到目标产物C-18(94mg,收率96％)为亮黄色油状液体。1HNMR(400MHz,CDCl3)δ8.14–8.05(m,2H),7.59–7.53(m,1H),7.54–7.49(m,2H),7.49–7.43(m,2H),7.43–7.33(m,3H),6.62–6.56(m,2H),6.37–6.30(m,2H),3.67(s,3H).13C NMR(100MHz,CDCl3)δ185.18,165.08,157.64,140.23,132.83,132.81,132.24,131.13,129.97,129.62,128.55,128.24,122.98,113.94,70.44,55.39.
实施例29
与实验1类似的方法，A-19(53mg,0.20mmol),N-溴代丁二酰亚胺(89mg,0.50mmol),乙腈为溶剂，室温下反应15min,得到目标产物C-19(76mg,收率89％)为黄色油状液体。1H NMR(400MHz,CDCl3)δ8.04(d,J＝8Hz,2H),7.53(t,J＝7Hz,1H),7.47–7.39(m,2H),6.88–6.81(m,2H),6.63(d,J＝8Hz,2H),3.76(s,3H),2.33(s,3H).13C NMR(100MHz,CDCl3)δ185.65,166.13,157.15,141.41,133.16,131.87,131.11,128.13,120.39,114.38,72.24,55.52,16.50.
实施例30
与实验1类似的方法，A-20(47mg,0.20mmol),N-溴代丁二酰亚胺(89mg,0.50mmol),乙腈为溶剂，室温下反应40min,得到目标产物C-20(73mg,收率93％)为浅黄色油状液体。1H NMR(400MHz,CD3OD)δ8.03(d,J＝8Hz,2H),7.59–7.51(m,1H),7.46(t,J＝7Hz,2H),7.33–7.25(m,2H),7.08(t,J＝7Hz,1H),6.61(d,J＝8Hz,2H),2.29(s,3H).13C NMR(100MHz,CD3OD)δ186.85,168.55,149.74,134.30,132.92,132.12,130.16,129.23,125.79,119.26,72.06,16.85.
实施例31
与实验1类似的方法，A-21(54mg,0.20mmol),N-溴代丁二酰亚胺(89mg,0.50mmol),乙腈为溶剂，室温下反应1h,得到目标产物C-21(81mg,收率94％)为黄色油状液体。1H NMR(400MHz,CD3OD)δ8.04–7.98(m,2H),7.59–7.52(m,1H),7.49–7.43(m,2H),7.31–7.24(m,2H),6.63–6.57(m,2H),2.30(s,3H).13C NMR(100MHz,CD3OD)δ186.70,169.33,148.26,134.36,132.81,132.08,131.18,130.23,129.27,121.02,71.73,17.02.
实施例32
与实验1类似的方法，A-22(40mg,0.20mmol),N-溴代丁二酰亚胺(89mg,0.50mmol),乙腈为溶剂，室温下反应1min,得到目标产物C-22(63mg,收率88％)为无色油状液体。1H NMR(400MHz,CDCl3)δ7.87–7.80(m,2H),7.50–7.43(m,1H),7.40–7.31(m,2H),2.93–2.86(m,1H),2.44(s,3H),0.85–0.79(m,2H),0.60–0.55(m,2H).13C NMR(100MHz,CDCl3)δ186.69,162.66,132.72,132.55,130.98,127.73,73.25,33.76,14.94,9.29.
实施例33
与实验1类似的方法，A-23(47mg,0.20mmol),N-溴代丁二酰亚胺(89mg,0.50mmol),乙腈为溶剂，室温下反应1min,得到目标产物C-23(68mg,收率87％)为黄色油状液体。1H NMR(400MHz,CDCl3)δ6.90–6.85(m,2H),6.76–6.67(m,2H),4.36(q,J＝7Hz,2H),3.79(s,3H),2.26(s,3H),1.33(t,J＝7Hz,3H).13C NMR(100MHz,CDCl3)δ164.75,164.55,157.04,141.58,120.71,114.34,64.35,63.30,55.56,15.78,13.99.
实施例34
与实验1类似的方法，A-24(41mg,0.20mmol),N-溴代丁二酰亚胺(89mg,0.50mmol),乙腈为溶剂，室温下反应15min,得到目标产物C-24(46mg,收率64％)为淡黄色油状液体。1H NMR(400MHz,CDCl3)δ6.89–6.86(m,2H),6.71(d,J＝8Hz,2H),3.79(s,3H),2.59(s,3H),2.33(s,3H).13C NMR(100MHz,CDCl3)δ192.81,166.27,157.29,141.04,120.88,114.39,73.29,55.58,25.75,16.29.
以上所述实施例是本发明的优选实例，应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明所述原理的前提下，还可以做出一些改进，这些改进也应视为本发明的保护范围。