一种咪唑并[1,2-a]吡啶的芳基化方法转让专利
申请号 : CN201610906165.4
文献号 : CN106565704B
文献日 : 2018-10-23
发明人 : 邵黎雄 , 陆建梅 , 刘青鲜 , 何邦岳
申请人 : 温州大学
摘要 :
本发明提供了一种咪唑并[1,2‑a]吡啶的芳基化方法：氮气保护下，将式(1)所示咪唑并[1,2‑a]吡啶、式(2)所示芳基/杂芳基氯化物、催化剂氮杂环卡宾‑钯络合物、碱性物质、反应溶剂混合，于80～150℃反应12～24h，之后反应液经后处理，得到产物式(3)所示芳基化咪唑并[1,2‑a]吡啶；本发明发展了新颖的催化体系，催化剂稳定、易得，能使稳定、价格低廉的芳基/杂芳基氯化物参与反应，具有反应操作简单、成本低廉、产物收率和纯度高等诸多优点，是合成芳基化咪唑并[1,2‑a]吡啶类化合物的全新方法，为该类化合物的合成提供了新的路线，具有良好的研究价值和工业应用产景；
权利要求 :
1.一种咪唑并[1,2-a]吡啶的芳基化方法，其特征在于，所述的方法为：氮气保护下，将式(1)所示咪唑并[1,2-a]吡啶、式(2)所示芳基/杂芳基氯化物、催化剂氮杂环卡宾-钯络合物、碱性物质、反应溶剂混合，于80～150℃反应12～24h，之后反应液经后处理，得到产物式(3)所示芳基化咪唑并[1,2-a]吡啶；
式(1)、(2)或(3)中，
R1为氢、C1～C5烷基、C1～C5烷氧基或卤素；
R2为氢、C1～C5烷基、C1～C5烷氧基、C1～C5烯基或卤素；
Ar表示C5～C10芳基或C5～C10杂芳基；
所述式(1)所示咪唑并[1,2-a]吡啶与式(2)所示芳基/杂芳基氯化物、催化剂氮杂环卡宾-钯络合物、碱性物质的投料物质的量之比为1：1～5：0.001～0.1：1～5；
所述的碱性物质选自叔丁醇钾、叔丁醇钠、氢氧化钾中的任意一种；
所述的反应溶剂为四氢呋喃、二氧六环、甲苯或N,N-二甲基乙酰胺；
所述的催化剂氮杂环卡宾-钯络合物选自式(4)～(7)之一所示的化合物：
2.如权利要求1所述的咪唑并[1,2-a]吡啶的芳基化方法，其特征在于，所述的式(1)所示咪唑并[1,2-a]吡啶选自下列式(1a)～(1e)所示化合物之一：
3.如权利要求1所述的咪唑并[1,2-a]吡啶的芳基化方法，其特征在于，所述的式(2)所示芳基/杂芳基氯化物选自下列式(2a)～(2l)所示化合物之一：
4.如权利要求1所述的咪唑并[1,2-a]吡啶的芳基化方法，其特征在于，所述式(1)所示咪唑并[1,2-a]吡啶与式(2)所示芳基/杂芳基氯化物、催化剂氮杂环卡宾-钯络合物、碱性物质的投料物质的量之比为1：1.5～2.0：0.1～0.05：2～3。
5.如权利要求1所述的咪唑并[1,2-a]吡啶的芳基化方法，其特征在于，所述反应溶剂的体积用量以式(1)所示咪唑并[1,2-a]吡啶的质量计为5～10mL/g。
6.如权利要求1所述的咪唑并[1,2-a]吡啶的芳基化方法，其特征在于，所述反应液的后处理方法为：反应结束后，将反应液自然冷却至室温，然后用旋转蒸发仪除去反应液中的溶剂，残留物进行常规柱色谱分离纯化，以300～400目硅胶为柱填料，石油醚与乙酸乙酯体积比1～4：1的混合液以及乙酸乙酯为洗脱剂进行梯度洗脱，柱层析过程中使用TLC跟踪监测，收集含目标化合物的洗脱液，蒸除溶剂并干燥，即得产物。
说明书 :
一种咪唑并[1,2-a]吡啶的芳基化方法
(一)技术领域
[0001] 本发明涉及一种通过C-H键直接官能团化合成芳基化咪唑并[1,2-a]吡啶的方法，属于有机化学合成领域。(二)背景技术
[0002] 咪唑并[1,2-a]吡啶骨架广泛存在于大量杂环化合物中，并且它们是一些重要药物如唑吡坦、阿吡坦和佐利咪啶的关键骨架。由于这类化合物具有广泛的生物活性，因此设计发展此类化合物具有非常重要的现实意义。
[0003] 近年来，过渡金属催化杂环化合物的C-H键直接官能团化，由于步骤简洁、原料易得，引起了大家的广泛关注，并取得了长足的进展。毫无疑问地，在过去几年中，通过C-H键直接官能团化合成芳基化咪唑并[1,2-a]吡啶也得到了一定的发展。公开报导中的芳基化试剂包括芳基卤化物、芳基硼酸、芳基磺酸酯和芳烃。从理论上来看，芳烃是最理想的芳基化试剂，但使用这种试剂时需要大量的芳烃作为反应溶剂和反应试剂，原子经济性很差，而且直接采用芳烃作为芳基化试剂，反应的区域选择性很差。接下来，理想的芳基化试剂为芳基卤化物，这种试剂相对其它几种来说，价格相对低廉，且简便易得，反应位点容易控制。但是，就公开的报导来看，采用芳基卤化物为芳基化试剂时，由于催化体系的限制，目前只能使用活性较高、但价格也相对较高的芳基溴化物和碘化物为芳基化试剂，而以活性虽然较低，但价格相当低廉的芳基氯化物为芳基化试剂的报导很少。而且，在已公开的以芳基氯化物为芳基化试剂的报导中，存在明显的缺陷，并因此限制了它们在有机合成中的应用价值，例如：(1)底物局限性大；(2)催化剂和配体的用量大；(3)反应中必须使用对空气敏感、不易制备、毒性较大的膦配体，且配体不易合成，导致反应操作步骤复杂。
[0004] 基于以上原因，探索稳定、易得、高效的催化剂，以价格低廉的芳基氯化物为底物，合成芳基化咪唑并[1,2-a]吡啶，仍具有很大的研究发展空间，这也正是本发明得以完成的基础和动力所在。(三)发明内容
[0005] 为了克服上述合成芳基化咪唑并[1,2-a]吡啶中的诸多缺陷，本发明提供了一种新的咪唑并[1,2-a]吡啶的芳基化方法。
[0006] 本发明采用如下技术方案：
[0007] 一种咪唑并[1,2-a]吡啶的芳基化方法，所述的方法为：
[0008] 氮气保护下，将式(1)所示咪唑并[1,2-a]吡啶、式(2)所示芳基/杂芳基氯化物、催化剂氮杂环卡宾-钯络合物、碱性物质、反应溶剂混合，于80～150℃反应12～24h，之后反应液经后处理，得到产物式(3)所示芳基化咪唑并[1,2-a]吡啶；
[0009] 所述式(1)所示咪唑并[1,2-a]吡啶与式(2)所示芳基/杂芳基氯化物、催化剂氮杂环卡宾-钯络合物、碱性物质的投料物质的量之比为1：1～5：0.001～0.1：1～5，优选1：1.5～2.0：0.1～0.05：2～3；
[0010] 所述反应溶剂的体积用量以式(1)所示咪唑并[1,2-a]吡啶的质量计为5～10mL/g；
[0011]
[0012] 式(1)、(2)或(3)中，
[0013] R1为氢、C1～C5烷基、C1～C5烷氧基或卤素；
[0014] R2为氢、C1～C5烷基、C1～C5烷氧基、C1～C5烯基或卤素；
[0015] Ar表示C5～C10芳基或C5～C10杂芳基，例如：苯基或吡啶基。
[0016] 进一步，式(1)中，R1可位于咪唑并[1,2-a]吡啶骨架的5-位、6-位、7-位或8-位，咪唑并[1,2-a]吡啶骨架的编号顺序如下：
[0017]
[0018] 具体的，优选所述的式(1)所示咪唑并[1,2-a]吡啶选自下列式(1a)～(1e)所示化合物之一：
[0019]
[0020] 进一步，式(2)中，R2可位于芳环或杂芳环上Cl的邻位、间位或对位。
[0021] 具体的，优选所述的式(2)所示芳基/杂芳基氯化物选自下列式(2a)～(2l)所示化合物之一：
[0022]
[0023] 本发明所述的碱性物质可选自叔丁醇钾、叔丁醇钠、叔丁醇锂、碳酸钾、碳酸钠、碳酸锂、碳酸铯、氢氧化钾、氢氧化钠、氢氧化铯、磷酸钾、磷酸钠、碳酸氢钾、碳酸氢钠中的任意一种，优选为叔丁醇钠。
[0024] 本发明所述的反应溶剂可以为四氢呋喃、2-甲基四氢呋喃、二氧六环、甲苯、N,N-二甲基乙酰胺、N,N-二甲基甲酰胺、乙腈、1,2-二氯乙烷、乙醚、乙醇、甲醇、丙醇、异丙醇、丁醇、丙酮、水中的任意一种或两种以上任意比例的混合溶剂，优选为四氢呋喃或二氧六环。
[0025] 本发明所述方法的反应时间并无特别的限定，例如可通过液相色谱、色谱-质谱联用方法或TLC检测原料残留量多少而确定合适的反应时间，通常为12～24h。
[0026] 本发明所述方法中，反应结束后反应液的后处理可采用有机合成领域中任何公知的常规处理手段，例如结晶、重结晶、柱色谱提纯、萃取等中的任何一种处理手段或多种处理手段的组合。具体的，可按照如下方法进行后处理：反应结束后，将反应液自然冷却至室温(20～30℃)，然后用旋转蒸发仪除去反应液中的溶剂，残留物进行常规柱色谱分离纯化，以300～400目硅胶为柱填料，石油醚与乙酸乙酯体积比1～4：1的混合液以及乙酸乙酯(纯)为洗脱剂进行梯度洗脱，柱层析过程中使用TLC跟踪监测，收集含目标化合物的洗脱液，蒸除溶剂并干燥，即得产物。
[0027] 本发明中，所述的催化剂氮杂环卡宾-钯络合物的非限定性例子如式(4)～(23)之一所示，这些催化剂均能通过公知的方法简洁地合成得到：
[0028]
[0029]
[0030] 本发明的有益效果在于：本发明使用氮杂环卡宾-钯络合物为催化剂，在碱性物质存在下，式(1)所示咪唑并[1,2-a]吡啶与式(2)所示芳基/杂芳基氯化物可发生C-H键直接官能团化反应，得到相应的芳基化咪唑并[1,2-a]吡啶类化合物。所述方法中，发展了新颖的催化体系，催化剂稳定、易得，能使稳定、价格低廉的芳基/杂芳基氯化物参与反应，具有反应操作简单、成本低廉、产物收率和纯度高等诸多优点，是合成芳基化咪唑并[1,2-a]吡啶类化合物的全新方法，为该类化合物的合成提供了新的路线，具有良好的研究价值和工业应用产景。(四)具体实施方式
[0031] 下面通过实施例的方式进一步说明本发明，但并不因此将本发明限制在所述的实施例范围之中。本发明所述合成方法中，室温为25℃。
[0032] 实施例
[0033] 除非特殊限定，普遍反应条件如下：
[0034] 氮气保护下，将氮杂环卡宾-钯络合物(6.5mg,2.0mol％)，叔丁醇钠(144mg,3.0equiv)，四氢呋喃(0.5mL)，咪唑并[1,2-a]吡啶(52μL,0.5mmol)和氯苯(76μL,
0.75mmol)依次加入封管中。将混合物120℃下加热反应12小时。停止反应，将混合物自然冷却至室温，旋转蒸发仪除去溶剂，残留物用快速柱层析分离得到纯净产物，所有产率为分离纯化后产物的产率。
0.75mmol)依次加入封管中。将混合物120℃下加热反应12小时。停止反应，将混合物自然冷却至室温，旋转蒸发仪除去溶剂，残留物用快速柱层析分离得到纯净产物，所有产率为分离纯化后产物的产率。
[0035] 表格1.反应条件优化
[0036]
[0037]
[0038] a所有反应均以1a(0.5mmol)，2a(0.75mmol)，4(2.0mol％)，碱(3.0当量)，溶剂(0.5mL)在120℃下反应12小时。b分离收率。
[0039] 表格2.氮杂环卡宾-钯络合物4催化1a与2的反应。
[0040]
[0041]
[0042] a除非特别说明，所有反应均以1a(0.5mmol)，2(0.75mmol)，4(2.0mol％)，NaOtBu(3.0当量)在四氢呋喃(0.5mL)中反应。b分离收率。c4(4.0mol％)。
[0043] 表格3.氮杂环卡宾-钯络合物4催化1与2的反应。
[0044]
[0045]
[0046] a除非特别说明，所有反应均以1(0.5mmol)，2(0.75mmol)，4(2.0mol％)，NaOtBu(3.0当量)，四氢呋喃(0.5mL)在120℃反应12小时。b分离收率。c130℃.
[0047] 对比例
[0048] 将2-甲基咪唑并[1，2-a]吡啶2i(66mg，0.5mmol)，氯苯2a(78.4mg，0.7mmol)，醋酸钯(2.5mol％)，丁基二金刚烷基膦(10mol％)，碳酸铯(1.5mmol)和N-甲基吡咯烷酮(2mL)在油浴120℃中加热反应24小时。反应结束后，加入8毫升水。水溶液用乙醚萃取(3×8mL)，有机相合并后用无水硫酸镁干燥。溶剂浓缩后用柱层析分离得到产物。
[0049] 从上述文献报导结果可知，与本发明实施例相比，此反应底物局限性大，即咪唑并[1,2-a]吡啶2-位上必须有甲基取代基；所用配体合成步骤复杂，且对空气和水汽敏感，导致操作不易；反应所使用的溶剂毒性较大，对环境危害严重；反应后处理复杂，需结合萃取、干燥等步骤。
[0050] 附：本发明实施例所合成产物的表征数据
[0051] 化合物3a：黄色固体。1H NMR(500MHz,CDCl3,TMS)δ8.31(d,J＝7.0Hz,1H),7.69(s,1H),7.66(d,J＝9.0Hz,1H),7.55-7.53(m,2H),7.49(t,J＝8.0Hz,2H),7.41-7.38(m,1H),
7.19-7.15(m,1H),6.77(td,J＝7.0,1.0Hz,1H).13C NMR(125MHz,CDCl3)δ146.0,132.3,
129.13,129.08,128.0,127.8,125.6,124.1,123.2,118.1,112.4.
7.19-7.15(m,1H),6.77(td,J＝7.0,1.0Hz,1H).13C NMR(125MHz,CDCl3)δ146.0,132.3,
129.13,129.08,128.0,127.8,125.6,124.1,123.2,118.1,112.4.
[0052] 化合物3b：棕色液体。1H NMR(500MHz,CDCl3,TMS)δ7.83(dt,J＝6.5,1.0Hz,1H),7.66(t,J＝4.5Hz,2H),7.47-7.41(m,2H),7.18(ddd,J＝9.0,6.5,1.0Hz,1H),7.08(td,J＝
7.5,1.0Hz,1H),7.05(d,J＝8.0Hz,1H),6.75(td,J＝7.0,1.0Hz,1H),3.80(s,3H).13C NMR(125MHz,CDCl3)δ157.1,145.9,133.1,131.8,130.2,125.2,123.8,123.0,121.0,118.0,
117.7,111.5,111.2,55.4.
7.5,1.0Hz,1H),7.05(d,J＝8.0Hz,1H),6.75(td,J＝7.0,1.0Hz,1H),3.80(s,3H).13C NMR(125MHz,CDCl3)δ157.1,145.9,133.1,131.8,130.2,125.2,123.8,123.0,121.0,118.0,
117.7,111.5,111.2,55.4.
[0053] 化合物3c：白色固体。1H NMR(500MHz,CDCl3,TMS)δ8.35(d,J＝6.5Hz,1H),7.70(s,1H),7.66(d,J＝9.0Hz,1H),7.41(t,J＝8.0Hz,1H),7.18(t,J＝8.0Hz,1H),7.13(d,J＝
7.5Hz,1H),7.08(s,1H),6.94(dd,J＝8.0,2.5Hz,1H),6.79(t,J＝6.5Hz,1H),3.85(s,3H).13C NMR(125MHz,CDCl3)δ160.0,146.0,132.4,130.4,130.1,125.4,124.1,123.3,120.0,
118.0,113.5,113.3,112.4,55.2.
7.5Hz,1H),7.08(s,1H),6.94(dd,J＝8.0,2.5Hz,1H),6.79(t,J＝6.5Hz,1H),3.85(s,3H).13C NMR(125MHz,CDCl3)δ160.0,146.0,132.4,130.4,130.1,125.4,124.1,123.3,120.0,
118.0,113.5,113.3,112.4,55.2.
[0054] 化合物3d：白色固体。1H NMR(500MHz,CDCl3,TMS)δ8.24(d,J＝7.0Hz,1H),7.65(d,J＝9.5Hz,1H),7.62(s,1H),7.45(d,J＝8.5Hz,2H),7.16(t,J＝8.0Hz,1H),7.04(d,J＝8.5Hz,2H),6.77(t,J＝7.0Hz,1H),3.86(s,3H).13C NMR(125MHz,CDCl3)δ159.4,145.6,
131.8,129.5,125.4,123.8,123.1,121.3,117.9,114.5,112.2,55.2.
131.8,129.5,125.4,123.8,123.1,121.3,117.9,114.5,112.2,55.2.
[0055] 化合物3e：棕色液体。1H NMR(500MHz,CDCl3,TMS)δ7.76(d,J＝7.0Hz,1H),7.69(d,J＝9.0Hz,1H),7.62(s,1H),7.41-7.30(m,4H),7.20(ddd,J＝9.0,6.5,1.0Hz,1H),6.77(t,J＝6.5Hz,1H),2.17(s,3H).13C NMR(125MHz,CDCl3)δ145.4,138.2,132.8,131.1,130.6,129.1,128.2,126.2,124.6,123.9,123.6,118.0,112.2,19.7.
[0056] 化合物3f：棕色液体。1H NMR(500MHz,CDCl3,TMS)δ8.32(d,J＝7.0Hz,1H),7.67(s,1H),7.65(d,J＝9.0Hz,1H),7.40-7.33(m,3H),7.21(d,J＝7.5Hz,1H),7.18-7.15(m,1H),
6.77(td,J＝7.0,1.0Hz,1H),2.42(s,3H).13C NMR(125MHz,CDCl3)δ145.9,138.9,132.3,
129.1,129.0,128.8,128.6,125.7,124.9,124.0,123.3,118.0,112.3,21.3.
6.77(td,J＝7.0,1.0Hz,1H),2.42(s,3H).13C NMR(125MHz,CDCl3)δ145.9,138.9,132.3,
129.1,129.0,128.8,128.6,125.7,124.9,124.0,123.3,118.0,112.3,21.3.
[0057] 化合物3g：黄色固体。1H NMR(500MHz,CDCl3,TMS)δ8.31(d,J＝7.0Hz,1H),7.68-7.66(m,2H),7.45(d,J＝8.0Hz,2H),7.33(d,J＝8.0Hz,2H),7.20-7.17(m,1H),6.80(t,J＝
6.5Hz,1H),2.44(s,3H).13C NMR(125MHz,CDCl3)δ145.9,138.2,132.1,129.9,128.0,
126.2,125.7,124.1,123.3,118.1,112.4,21.3.
6.5Hz,1H),2.44(s,3H).13C NMR(125MHz,CDCl3)δ145.9,138.2,132.1,129.9,128.0,
126.2,125.7,124.1,123.3,118.1,112.4,21.3.
[0058] 化合物3h：棕色液体。1H NMR(500MHz,CDCl3,TMS)δ8.01-7.99(m,1H),7.74(s,1H),7.68(d,J＝9.0Hz,1H),7.49(t,J＝7.5Hz,1H),7.42(dd,J＝13.5,7.5Hz,1H),7.31-7.19(m,3H),6.81(t,J＝7.5Hz,1H).13C NMR(125MHz,CDCl3)δ159.7(d,JC-F＝247.375Hz),
146.2,133.7(d,JC-F＝0.75Hz),131.1(d,JC-F＝3.125Hz),130.2(d,JC-F＝8.125Hz),124.7(d,JC-F＝3.5Hz),124.3,124.2(d,JC-F＝4.625Hz),119.9,117.8,116.9(d,JC-F＝15.0Hz),
116.1(d,JC-F＝21.375Hz),112.3.MS(ESI):213[M+H]+；HRMS(ESI)calcd for C13H10FN2[M++
H]:213.0823；found:213.0840；IR(neat)ν1635,1542,1497,1483,1469,1450,1351,1301,
1270,1256,1216,1177,1146,1118,1090,1008,970,897,865,814,779,753,737cm-1.[0059] 化合物3i：棕色液体。1H NMR(500MHz,CDCl3,TMS)δ8.33(d,J＝7.0Hz,1H),7.72(s,
1H),7.67(d,J＝9.0Hz,1H),7.47(td,J＝8.0,6.0Hz,1H),7.34(dt,J＝7.5,1.0Hz,1H),
7.26(dt,J＝9.5,2.0Hz,1H),7.21(ddd,J＝9.0,6.5,1.0Hz,1H),7.10(tdd,J＝8.5,2.5,
1.0Hz,1H),6.83(td,J＝7.0,1.0Hz,1H).13C NMR(125MHz,CDCl3)δ163.0(d,JC-F＝
245.875Hz),146.3,132.9,131.2(d,JC-F＝8.375Hz),130.8(d,JC-F＝8.625Hz),124.4,
123.3(d,JC-F＝3.0Hz),123.1,118.2,114.9(d,JC-F＝21.0Hz),114.5(d,JC-F＝22.125Hz),
112.7.MS(ESI):213[M+H]+；HRMS(ESI)calcd for C13H10FN2[M+H]+:213.0823；found:
213.0840；IR(neat)ν1610,1582,1495,1469,1436,1354,1295,1264,1208,1157,1129,
1115,848,791,750,734cm-1.
146.2,133.7(d,JC-F＝0.75Hz),131.1(d,JC-F＝3.125Hz),130.2(d,JC-F＝8.125Hz),124.7(d,JC-F＝3.5Hz),124.3,124.2(d,JC-F＝4.625Hz),119.9,117.8,116.9(d,JC-F＝15.0Hz),
116.1(d,JC-F＝21.375Hz),112.3.MS(ESI):213[M+H]+；HRMS(ESI)calcd for C13H10FN2[M++
H]:213.0823；found:213.0840；IR(neat)ν1635,1542,1497,1483,1469,1450,1351,1301,
1270,1256,1216,1177,1146,1118,1090,1008,970,897,865,814,779,753,737cm-1.[0059] 化合物3i：棕色液体。1H NMR(500MHz,CDCl3,TMS)δ8.33(d,J＝7.0Hz,1H),7.72(s,
1H),7.67(d,J＝9.0Hz,1H),7.47(td,J＝8.0,6.0Hz,1H),7.34(dt,J＝7.5,1.0Hz,1H),
7.26(dt,J＝9.5,2.0Hz,1H),7.21(ddd,J＝9.0,6.5,1.0Hz,1H),7.10(tdd,J＝8.5,2.5,
1.0Hz,1H),6.83(td,J＝7.0,1.0Hz,1H).13C NMR(125MHz,CDCl3)δ163.0(d,JC-F＝
245.875Hz),146.3,132.9,131.2(d,JC-F＝8.375Hz),130.8(d,JC-F＝8.625Hz),124.4,
123.3(d,JC-F＝3.0Hz),123.1,118.2,114.9(d,JC-F＝21.0Hz),114.5(d,JC-F＝22.125Hz),
112.7.MS(ESI):213[M+H]+；HRMS(ESI)calcd for C13H10FN2[M+H]+:213.0823；found:
213.0840；IR(neat)ν1610,1582,1495,1469,1436,1354,1295,1264,1208,1157,1129,
1115,848,791,750,734cm-1.
[0060] 化合物3j：棕色液体。1H NMR(500MHz,CDCl3,TMS)δ8.24(d,J＝7.0Hz,1H),7.68(d,J＝10.0Hz,2H),7.55-7.51(m,2H),7.25-7.19(m,3H),6.82(td,J＝7.0,1.0Hz,1H).13C NMR(125MHz,CDCl3)δ162.4(d,JC-F＝247.0Hz),145.9,132.4,129.9(d,JC-F＝8.125Hz),125.2(d,JC-F＝3.125Hz),124.5,124.1,123.0,118.2,116.2(d,JC-F＝21.625Hz),112.5.[0061] 化合物3k：棕色液体。1H NMR(500MHz,CDCl3,TMS)δ8.35(d,J＝7.0Hz,1H),7.71(s,1H),7.68(d,J＝9.0Hz,1H),7.56(d,J＝8.5Hz,2H),7.53(d,J＝8.5Hz,2H),7.21(t,J＝
8.0Hz,1H),6.83(d,J＝7.0Hz,1H),6.78(dd,J＝17.5,11.0Hz,1H),5.83(d,J＝17.5Hz,
13
1H),5.33(d,J＝11.0Hz,1H). C NMR(125MHz,CDCl3)δ146.1,137.3,136.0,132.5,128.5,
127.8,126.9,125.4,124.2,123.3,118.1,114.5,112.5.MS(ESI):221[M+H]+；HRMS(ESI)calcd for C15H13N2[M+H]+:221.1073；found:221.1091；IR(neat)ν1627,1604,1540,1483,
1407,1351,1301,1273,1253,1163,1149,1129,1115,1008,989,962,910,903,893,858,-1
848,843,754,738,736cm .
8.0Hz,1H),6.83(d,J＝7.0Hz,1H),6.78(dd,J＝17.5,11.0Hz,1H),5.83(d,J＝17.5Hz,
13
1H),5.33(d,J＝11.0Hz,1H). C NMR(125MHz,CDCl3)δ146.1,137.3,136.0,132.5,128.5,
127.8,126.9,125.4,124.2,123.3,118.1,114.5,112.5.MS(ESI):221[M+H]+；HRMS(ESI)calcd for C15H13N2[M+H]+:221.1073；found:221.1091；IR(neat)ν1627,1604,1540,1483,
1407,1351,1301,1273,1253,1163,1149,1129,1115,1008,989,962,910,903,893,858,-1
848,843,754,738,736cm .
[0062] 化合物3l：白色固体。熔点：80-81℃。1H NMR(500MHz,CDCl3,TMS)δ9.93(d,J＝7.0Hz,1H),8.64(d,J＝5.0Hz,1H),8.13(s,1H),7.72-7.68(m,3H),7.2t(t,J＝8.0Hz,1H),
7.16-7.11(m,1H),6.92(t,J＝7.0Hz,1H).13C NMR(125MHz,CDCl3)δ150.5,148.6,147.4,
136.4,134.5,128.0,125.4,123.5,120.8,120.3,117.4,112.8.MS(ESI):196[M+H]+；HRMS(ESI)calcd for C12H10N3[M+H]+:196.0869；found:196.0879；IR(neat)ν1587,1531,1495,
1444,1438,1360,1348,1320,1306,1273,1261,1185,1171,1126,1093,1014,992,968,888,
851,837,782,751,736,716cm-1.
7.16-7.11(m,1H),6.92(t,J＝7.0Hz,1H).13C NMR(125MHz,CDCl3)δ150.5,148.6,147.4,
136.4,134.5,128.0,125.4,123.5,120.8,120.3,117.4,112.8.MS(ESI):196[M+H]+；HRMS(ESI)calcd for C12H10N3[M+H]+:196.0869；found:196.0879；IR(neat)ν1587,1531,1495,
1444,1438,1360,1348,1320,1306,1273,1261,1185,1171,1126,1093,1014,992,968,888,
851,837,782,751,736,716cm-1.
[0063] 化合物3m：棕色液体。1H NMR(500MHz,CDCl3,TMS)δ8.20(d,J＝7.0Hz,1H),7.61(s,1H),7.53-7.47(m,4H),7.41-7.36(m,2H),6.61(d,J＝7.5Hz,1H),2.39(s,3H).13C NMR(125MHz,CDCl3)δ146.5,135.0,132.0,129.4,129.0,127.8,127.7,125.1,122.4,116.4,
115.0,21.1.
115.0,21.1.
[0064] 化合物3n：棕色液体。1H NMR(500MHz,CDCl3,TMS)δ8.22(d,J＝7.0Hz,1H),7.62(s,1H),7.40-7.31(m,2H),7.11(d,J＝7.5Hz,1H),7.06(s,1H),6.92(dd,J＝8.0,1.5Hz,1H),
6.61(d,J＝7.0Hz,1H),3.84(s,3H),2.38(s,3H).13C NMR(125MHz,CDCl3)δ159.9,146.4,
135.0,132.0,130.5,130.0,124.8,122.5,119.8,116.3,115.0,113.3,113.0,55.1,
21.0.MS(ESI):239[M+H]+；HRMS(ESI)calcd for C15H15N2O[M+H]+:239.1179；found:
239.1200；IR(neat)ν1646,1599,1573,1542,1492,1464,1433,1340,1298,1292,1287,
1233,1185,1166,1141,1110,1042,989,845,776,746,698cm-1.
6.61(d,J＝7.0Hz,1H),3.84(s,3H),2.38(s,3H).13C NMR(125MHz,CDCl3)δ159.9,146.4,
135.0,132.0,130.5,130.0,124.8,122.5,119.8,116.3,115.0,113.3,113.0,55.1,
21.0.MS(ESI):239[M+H]+；HRMS(ESI)calcd for C15H15N2O[M+H]+:239.1179；found:
239.1200；IR(neat)ν1646,1599,1573,1542,1492,1464,1433,1340,1298,1292,1287,
1233,1185,1166,1141,1110,1042,989,845,776,746,698cm-1.
[0065] 化合物3o：棕色液体。1H NMR(500MHz,CDCl3,TMS)δ8.22(d,J＝7.0Hz,1H),7.60(s,1H),7.41-7.33(m,4H),7.20(d,J＝7.0Hz,1H),6.62(dd,J＝7.0,1.5Hz,1H),2.43(s,3H),
13
2.40(s,3H). C NMR(125MHz,CDCl3)δ146.5,138.9,134.9,132.1,129.4,129.0,128.6,
128.5,125.2,124.8,122.6,116.4,115.0,21.4,21.1.MS(ESI):223[M+H]+；HRMS(ESI)calcd for C15H15N2[M+H]+:223.1230；found:223.1247；IR(neat)ν1647,1608,1544,1497,
1463,1346,1332,1301,1268,1184,1167,1134,1114,1033,905,884,858,842,789,779,
742,703cm-1.
13
2.40(s,3H). C NMR(125MHz,CDCl3)δ146.5,138.9,134.9,132.1,129.4,129.0,128.6,
128.5,125.2,124.8,122.6,116.4,115.0,21.4,21.1.MS(ESI):223[M+H]+；HRMS(ESI)calcd for C15H15N2[M+H]+:223.1230；found:223.1247；IR(neat)ν1647,1608,1544,1497,
1463,1346,1332,1301,1268,1184,1167,1134,1114,1033,905,884,858,842,789,779,
742,703cm-1.
[0066] 化合物3p：黄色固体。熔点：99-100℃。1H NMR(500MHz,CDCl3,TMS)δ7.89(dd,J＝7.0,3.0Hz,1H),7.66(s,1H),7.49(td,J＝7.5,1.5Hz,1H),7.44-7.39(m,2H),7.29-7.21(m,2H),6.67-6.64(m,1H),2.41(s,3H).13C NMR(125MHz,CDCl3)δ159.6(d,JC-F＝
247.125Hz),146.7,135.4,133.4,131.0(d,JC-F＝3.25Hz),130.0(d,JC-F＝8.125Hz),124.7(d,JC-F＝3.5Hz),123.5(d,JC-F＝4.75Hz),119.5,117.2(d,JC-F＝15.0Hz),116.2(d,JC-F＝+ +
1.875Hz),116.1,114.9,21.1.MS(ESI):227[M+H] ；HRMS(ESI)calcd for C14H12FN2[M+H] :
227.0979；found:227.0998；IR(neat)ν1647,1545,1496,1449,1340,1300,1275,1213,
1186,1139,1117,1092,975,867,848,825,810,787,758,748cm-1.
247.125Hz),146.7,135.4,133.4,131.0(d,JC-F＝3.25Hz),130.0(d,JC-F＝8.125Hz),124.7(d,JC-F＝3.5Hz),123.5(d,JC-F＝4.75Hz),119.5,117.2(d,JC-F＝15.0Hz),116.2(d,JC-F＝+ +
1.875Hz),116.1,114.9,21.1.MS(ESI):227[M+H] ；HRMS(ESI)calcd for C14H12FN2[M+H] :
227.0979；found:227.0998；IR(neat)ν1647,1545,1496,1449,1340,1300,1275,1213,
1186,1139,1117,1092,975,867,848,825,810,787,758,748cm-1.
[0067] 化合物3q：黄色固体。1H NMR(500MHz,CDCl3,TMS)δ8.12(d,J＝7.0Hz,1H),7.58(s,1H),7.49(dd,J＝8.5,6.0Hz,2H),7.41(s,1H),7.20(t,J＝8.5Hz,2H),6.64(d,J＝7.0Hz,
1H),2.41(s,3H).13C NMR(125MHz,CDCl3)δ162.3(d,JC-F＝246.75Hz),146.5,135.1,132.1,
129.7(d,JC-F＝8.125Hz),125.5(d,JC-F＝3.375Hz),124.1,122.2,116.5,116.2(d,JC-F＝
21.625Hz),115.2,21.1.
1H),2.41(s,3H).13C NMR(125MHz,CDCl3)δ162.3(d,JC-F＝246.75Hz),146.5,135.1,132.1,
129.7(d,JC-F＝8.125Hz),125.5(d,JC-F＝3.375Hz),124.1,122.2,116.5,116.2(d,JC-F＝
21.625Hz),115.2,21.1.
[0068] 化合物3r：棕色液体。1H NMR(500MHz,CDCl3,TMS)δ8.10(d,J＝1.0Hz,1H),7.63(s,1H),7.57-7.49(m,5H),7.40(tt,J＝7.0,1.5Hz,1H),7.03(dd,J＝9.0,1.5Hz,1H),2.29(s,
3H).13C NMR(125MHz,CDCl3)δ145.1,132.3,129.4,129.1,127.9,127.3,125.3,122.0,
120.8,117.4,18.2.
3H).13C NMR(125MHz,CDCl3)δ145.1,132.3,129.4,129.1,127.9,127.3,125.3,122.0,
120.8,117.4,18.2.
[0069] 化合物3s：黄色液体。1H NMR(500MHz,CDCl3,TMS)δ8.13(s,1H),7.64(s,1H),7.56(d,J＝9.0Hz,1H),7.42(t,J＝8.0Hz,1H),7.13(d,J＝7.5Hz,1H),7.08(s,1H),7.03(d,J＝9.0Hz,1H),6.94(dd,J＝8.5,2.5Hz,1H),3.86(s,3H),2.29(s,3H).13C NMR(125MHz,CDCl3)δ160.0,145.1,132.2,130.6,130.1,127.3,125.1,122.0,120.9,120.1,117.3,113.7,
113.1,55.2,18.2.MS(ESI):239[M+H]+；HRMS(ESI)calcd for C15H15N2O[M+H]+:239.1179；
found:239.1200；IR(neat)ν1607,1576,1540,1526,1500,1472,1427,1357,1332,1298,
1278,1239,1211,1157,1132,1042,978,844,799,781,753,696cm-1.
113.1,55.2,18.2.MS(ESI):239[M+H]+；HRMS(ESI)calcd for C15H15N2O[M+H]+:239.1179；
found:239.1200；IR(neat)ν1607,1576,1540,1526,1500,1472,1427,1357,1332,1298,
1278,1239,1211,1157,1132,1042,978,844,799,781,753,696cm-1.
[0070] 化合物3t：棕色液体。1H NMR(500MHz,CDCl3,TMS)δ8.09(s,1H),7.62(s,1H),7.55(d,J＝9.5Hz,1H),7.39(t,J＝7.5Hz,1H),7.34(d,J＝7.5Hz,2H),7.21(d,J＝7.5Hz,1H),7.02(dd,J＝9.5,1.5Hz,1H),2.43(s,3H),2.29(s,3H).13C NMR(125MHz,CDCl3)δ145.1,
138.9,132.2,129.3,128.9,128.7,128.6,127.1,125.4,124.9,121.9,120.9,117.3,21.4,
18.2.MS(ESI):223[M+H]+；HRMS(ESI)calcd for C15H15N2[M+H]+:223.1230；found:
223.1250；IR(neat)ν1606,1583,1541,1505,1460,1357,1340,1299,1265,1232,1153,-1
1134,1092,1042,856,845,786,753,703cm .
138.9,132.2,129.3,128.9,128.7,128.6,127.1,125.4,124.9,121.9,120.9,117.3,21.4,
18.2.MS(ESI):223[M+H]+；HRMS(ESI)calcd for C15H15N2[M+H]+:223.1230；found:
223.1250；IR(neat)ν1606,1583,1541,1505,1460,1357,1340,1299,1265,1232,1153,-1
1134,1092,1042,856,845,786,753,703cm .
[0071] 化合物3u：黄色固体。熔点：80-81℃。1H NMR(500MHz,CDCl3,TMS)δ7.78(s,1H),7.68(s,1H),7.58(d,J＝9.5Hz,1H),7.49(td,J＝7.5,1.5Hz,1H),7.45-7.40(m,1H),7.29-
7.22(m,2H),7.07(dd,J＝9.0,1.0Hz,1H),2.30(s,3H).13C NMR(125MHz,CDCl3)δ159.7(d,JC-F＝247.25Hz),145.3,133.6,131.1(d,JC-F＝3.25Hz),130.1(d,JC-F＝8.125Hz),127.5,
124.6(d,JC-F＝3.5Hz),121.9(d,JC-F＝6.375Hz),119.6,117.3,117.1,116.2(d,JC-F＝
21.5Hz),18.2.MS(ESI):227[M+H]+；HRMS(ESI)calcd for C14H12FN2[M+H]+:227.0979；
found:227.0998；IR(neat)ν1548,1528,1503,1469,1458,1436,1354,1334,1301,1264,
1230,1208,1152,1138,1118,1084,1037,965,930,861,830,809,795,768,753cm-1.[0072] 化合物3v：棕色液体。1H NMR(500MHz,CDCl3,TMS)δ8.11(d,J＝0.5Hz,1H),7.66(s,
1H),7.57(d,J＝9.5Hz,1H),7.47(td,J＝8.0,6.0Hz,1H),7.34(dt,J＝8.0,1.5Hz,1H),
7.26(ddd,J＝9.5,2.0,1.5Hz,1H),7.11-7.06(m,2H),2.32(s,3H).13C NMR(125MHz,CDCl3)δ163.1(d,JC-F＝245.625Hz),145.4,132.8,131.5(d,JC-F＝8.25Hz),130.7(d,JC-F＝
8.625Hz),127.6,124.1,123.4(d,JC-F＝2.875Hz),122.4,120.7,117.5,114.7(d,JC-F＝
21.125Hz),114.5(d,JC-F＝22.0Hz),18.3.
7.22(m,2H),7.07(dd,J＝9.0,1.0Hz,1H),2.30(s,3H).13C NMR(125MHz,CDCl3)δ159.7(d,JC-F＝247.25Hz),145.3,133.6,131.1(d,JC-F＝3.25Hz),130.1(d,JC-F＝8.125Hz),127.5,
124.6(d,JC-F＝3.5Hz),121.9(d,JC-F＝6.375Hz),119.6,117.3,117.1,116.2(d,JC-F＝
21.5Hz),18.2.MS(ESI):227[M+H]+；HRMS(ESI)calcd for C14H12FN2[M+H]+:227.0979；
found:227.0998；IR(neat)ν1548,1528,1503,1469,1458,1436,1354,1334,1301,1264,
1230,1208,1152,1138,1118,1084,1037,965,930,861,830,809,795,768,753cm-1.[0072] 化合物3v：棕色液体。1H NMR(500MHz,CDCl3,TMS)δ8.11(d,J＝0.5Hz,1H),7.66(s,
1H),7.57(d,J＝9.5Hz,1H),7.47(td,J＝8.0,6.0Hz,1H),7.34(dt,J＝8.0,1.5Hz,1H),
7.26(ddd,J＝9.5,2.0,1.5Hz,1H),7.11-7.06(m,2H),2.32(s,3H).13C NMR(125MHz,CDCl3)δ163.1(d,JC-F＝245.625Hz),145.4,132.8,131.5(d,JC-F＝8.25Hz),130.7(d,JC-F＝
8.625Hz),127.6,124.1,123.4(d,JC-F＝2.875Hz),122.4,120.7,117.5,114.7(d,JC-F＝
21.125Hz),114.5(d,JC-F＝22.0Hz),18.3.
[0073] 化合物3w：棕色液体。1H NMR(500MHz,CDCl3,TMS)δ8.01(s,1H),7.60(s,1H),7.57(d,J＝9.0Hz,1H),7.52(dd,J＝8.5,5.5Hz,2H),7.22(t,J＝8.5Hz,2H),7.06(dd,J＝9.0,1.0Hz,1H),2.32(s,3H).13C NMR(125MHz,CDCl3)δ162.5(d,JC-F＝246.75Hz),145.2,132.3,
130.1(d,JC-F＝8.125Hz),127.4,125.6(d,JC-F＝3.375Hz),124.3,122.3,120.7,117.6,
116.3(d,JC-F＝21.625Hz),18.3.MS(ESI):227[M+H]+；HRMS(ESI)calcd for C14H12FN2[M+H]+:227.0979；found:227.0985；IR(neat)ν1551,1531,1506,1490,1358,1338,1305,1229,
1151,1134,1095,962,931,840,835,811,798,759,744,735cm-1.
130.1(d,JC-F＝8.125Hz),127.4,125.6(d,JC-F＝3.375Hz),124.3,122.3,120.7,117.6,
116.3(d,JC-F＝21.625Hz),18.3.MS(ESI):227[M+H]+；HRMS(ESI)calcd for C14H12FN2[M+H]+:227.0979；found:227.0985；IR(neat)ν1551,1531,1506,1490,1358,1338,1305,1229,
1151,1134,1095,962,931,840,835,811,798,759,744,735cm-1.
[0074] 化合物3x：黄色固体。熔点：105-106℃。1H NMR(500MHz,CDCl3,TMS)δ8.13(d,J＝8.0Hz,1H),7.53(s,1H),7.52-7.46(m,4H),7.38-7.35(m,1H),6.91(d,J＝2.5Hz,1H),6.51(dd,J＝7.5,2.5Hz,1H),3.86(s,3H).13C NMR(125MHz,CDCl3)δ157.4,147.5,131.7,129.3,
129.0,127.7,127.6,124.7,123.8,107.4,95.1,55.3.MS(ESI):225[M+H]+；HRMS(ESI)calcd for C14H13N2O[M+H]+:225.1022；found:225.1038；IR(neat)ν1646,1601,1548,1507,
1475,1434,1301,1233,1162,1180,1139,1109,1028,972,947,907,864,841,831,776,766,
750,738,699cm-1.
129.0,127.7,127.6,124.7,123.8,107.4,95.1,55.3.MS(ESI):225[M+H]+；HRMS(ESI)calcd for C14H13N2O[M+H]+:225.1022；found:225.1038；IR(neat)ν1646,1601,1548,1507,
1475,1434,1301,1233,1162,1180,1139,1109,1028,972,947,907,864,841,831,776,766,
750,738,699cm-1.
[0075] 化合物3y：黄色固体。熔点：134-135℃。1H NMR(500MHz,CDCl3,TMS)δ8.16(d,J＝7.5Hz,1H),7.52(s,1H),7.38(t,J＝7.5Hz,1H),7.33(d,J＝8.5Hz,2H),7.20(d,J＝7.0Hz,
1H),6.91(d,J＝2.5Hz,1H),6.53(dd,J＝7.5,2.5Hz,1H),3.88(s,3H),2.43(s,3H).13C NMR(125MHz,CDCl3)δ157.5,147.6,139.0,131.8,129.4,129.0,128.7,128.5,125.0,124.8,
124.0,107.4,95.3,55.5,21.5.MS(ESI):239[M+H]+；HRMS(ESI)calcd for C15H15N2O[M+H]+:239.1179；found:239.1203；IR(neat)ν1652,1604,1537,1509,1478,1430,1348,1295,
1233,1183,1163,1042,951,866,860,840,809,774,743,702cm-1.
1H),6.91(d,J＝2.5Hz,1H),6.53(dd,J＝7.5,2.5Hz,1H),3.88(s,3H),2.43(s,3H).13C NMR(125MHz,CDCl3)δ157.5,147.6,139.0,131.8,129.4,129.0,128.7,128.5,125.0,124.8,
124.0,107.4,95.3,55.5,21.5.MS(ESI):239[M+H]+；HRMS(ESI)calcd for C15H15N2O[M+H]+:239.1179；found:239.1203；IR(neat)ν1652,1604,1537,1509,1478,1430,1348,1295,
1233,1183,1163,1042,951,866,860,840,809,774,743,702cm-1.
[0076] 化合物3z：棕色液体。1H NMR(500MHz,CDCl3,TMS)δ7.83(dd,J＝7.5,3.0Hz,1H),7.58(s,1H),7.49(td,J＝7.5,1.5Hz,1H),7.43-7.38(m,1H),7.28-7.21(m,2H),6.94(d,J＝2.0Hz,1H),6.55(dd,J＝7.5,2.5Hz,1H),3.88(s,3H).13C NMR(125MHz,CDCl3)δ159.6(d,JC-F＝246.875Hz),157.8,147.8,133.2,131.1(d,JC-F＝3.25Hz),130.0(d,JC-F＝8.125Hz),
124.9(d,JC-F＝4.875Hz),124.7(d,JC-F＝3.5Hz),119.1,117.2(d,JC-F＝15.0Hz),116.2(d,JC-F＝21.5Hz),107.3,95.0,55.4.MS(ESI):243[M+H]+；HRMS(ESI)calcd for C14H12FN2O[M+H]+:243.0928；found:243.0929；IR(neat)ν1647,1617,1575,1547,1494,1449,1338,1304,-1
1276,1212,1187,1145,1092,1036,975,946,937,869,849,825,809,789,761,747cm .[0077] 化合物3aa：黄色固体。熔点：132-133℃。1H NMR(500MHz,CDCl3,TMS)δ8.15(d,J＝
7.5Hz,1H),7.56(s,1H),7.45(td,J＝7.5,6.0Hz,1H),7.31-7.29(m,1H),7.22(dt,J＝
10.0,2.0Hz,1H),7.09-7.05(m,1H),6.92(d,J＝2.5Hz,1H),6.55(dd,J＝7.5,2.5Hz,1H),
3.88(s,3H).13C NMR(125MHz,CDCl3)δ163.1(d,JC-F＝245.625Hz),157.7,147.9,132.4,
131.5(d,JC-F＝8.25Hz),130.7(d,JC-F＝8.625Hz),123.7,123.1(d,JC-F＝2.875Hz),114.6,
114.3(d,JC-F＝22.125Hz),107.8,95.3,55.4.MS(ESI):243[M+H]+；HRMS(ESI)calcd for C14H12FN2O[M+H]+:243.0928；found:243.0963；IR(neat)ν1652,1610,1582,1542,1534,
1506,1483,1467,1436,1346,1337,1298,1236,1202,1180,1163,1143,1104,1022,951,
871,859,843,775,760,743cm-1.
124.9(d,JC-F＝4.875Hz),124.7(d,JC-F＝3.5Hz),119.1,117.2(d,JC-F＝15.0Hz),116.2(d,JC-F＝21.5Hz),107.3,95.0,55.4.MS(ESI):243[M+H]+；HRMS(ESI)calcd for C14H12FN2O[M+H]+:243.0928；found:243.0929；IR(neat)ν1647,1617,1575,1547,1494,1449,1338,1304,-1
1276,1212,1187,1145,1092,1036,975,946,937,869,849,825,809,789,761,747cm .[0077] 化合物3aa：黄色固体。熔点：132-133℃。1H NMR(500MHz,CDCl3,TMS)δ8.15(d,J＝
7.5Hz,1H),7.56(s,1H),7.45(td,J＝7.5,6.0Hz,1H),7.31-7.29(m,1H),7.22(dt,J＝
10.0,2.0Hz,1H),7.09-7.05(m,1H),6.92(d,J＝2.5Hz,1H),6.55(dd,J＝7.5,2.5Hz,1H),
3.88(s,3H).13C NMR(125MHz,CDCl3)δ163.1(d,JC-F＝245.625Hz),157.7,147.9,132.4,
131.5(d,JC-F＝8.25Hz),130.7(d,JC-F＝8.625Hz),123.7,123.1(d,JC-F＝2.875Hz),114.6,
114.3(d,JC-F＝22.125Hz),107.8,95.3,55.4.MS(ESI):243[M+H]+；HRMS(ESI)calcd for C14H12FN2O[M+H]+:243.0928；found:243.0963；IR(neat)ν1652,1610,1582,1542,1534,
1506,1483,1467,1436,1346,1337,1298,1236,1202,1180,1163,1143,1104,1022,951,
871,859,843,775,760,743cm-1.
[0078] 化合物3ab：黄色固体。熔点：135-136℃。1H NMR(500MHz,CDCl3,TMS)δ8.05(d,J＝7.5Hz,1H),7.50-7.47(m,3H),7.19(t,J＝9.0Hz,2H),6.92(d,J＝2.5Hz,1H),6.53(dd,J＝
7.5,2.0Hz,1H),3.88(s,3H).13C NMR(125MHz,CDCl3)δ162.3(d,JC-F＝246.625Hz),157.6,
147.5,131.8,129.7(d,JC-F＝8.0Hz),125.5(d,JC-F＝3.375Hz),123.7(d,JC-F＝20.0Hz),+
116.2(d,JC-F＝21.625Hz),107.6,95.2,55.5.MS(ESI):243[M+H] ；HRMS(ESI)calcd for C14H12FN2O[M+H]+:243.0928；found:243.0963；IR(neat)ν1649,1557,1545,1506,1491,
1475,1431,1345,1295,1219,1180,1156,1139,1106,1020,944,851,837,821,810,789,
775,736cm-1.
7.5,2.0Hz,1H),3.88(s,3H).13C NMR(125MHz,CDCl3)δ162.3(d,JC-F＝246.625Hz),157.6,
147.5,131.8,129.7(d,JC-F＝8.0Hz),125.5(d,JC-F＝3.375Hz),123.7(d,JC-F＝20.0Hz),+
116.2(d,JC-F＝21.625Hz),107.6,95.2,55.5.MS(ESI):243[M+H] ；HRMS(ESI)calcd for C14H12FN2O[M+H]+:243.0928；found:243.0963；IR(neat)ν1649,1557,1545,1506,1491,
1475,1431,1345,1295,1219,1180,1156,1139,1106,1020,944,851,837,821,810,789,
775,736cm-1.
[0079] 化合物3ac：棕色液体。1H NMR(500MHz,CDCl3,TMS)δ8.26(dd,J＝4.0,2.0Hz,1H),7.74(s,1H),7.65(dd,J＝10.0,5.5Hz,1H),7.56-7.52(m,4H),7.47-7.43(m,1H),7.15-
7.11(m,1H).13C NMR(125MHz,CDCl3)δ153.6(d,JC-F＝235.25Hz),143.8,133.7(d,JC-F＝
1.875Hz),129.3,128.8,128.5,127.8,127.0,118.6(d,JC-F＝9.125Hz),116.3(d,JC-F＝
25.625Hz),110.0(d,JC-F＝41.375Hz).
7.11(m,1H).13C NMR(125MHz,CDCl3)δ153.6(d,JC-F＝235.25Hz),143.8,133.7(d,JC-F＝
1.875Hz),129.3,128.8,128.5,127.8,127.0,118.6(d,JC-F＝9.125Hz),116.3(d,JC-F＝
25.625Hz),110.0(d,JC-F＝41.375Hz).
[0080] 化合物3ad：黄色固体。熔点：86-87℃。1H NMR(500MHz,CDCl3,TMS)δ8.29(d,J＝1.5Hz,1H),7.74(s,1H),7.65(dd,J＝10.0,5.5Hz,1H),7.45(t,J＝8.0Hz,1H),7.14-7.11(m,2H),7.06(s,1H),6.98(dd,J＝8.5,2.0Hz,1H),3.87(s,3H).13C NMR(125MHz,CDCl3)δ
160.2,153.5(d,JC-F＝235.375Hz),143.8,133.7,130.4,130.0,126.9,119.9,118.6(d,JC-F＝9.125Hz),116.3(d,JC-F＝25.625Hz),113.7(d,JC-F＝27.75Hz),110.3,110.0,55.3.MS(ESI):243[M+H]+；HRMS(ESI)calcd for C14H12FN2O[M+H]+:243.0928；found:243.0963；IR(neat)ν1652,1599,1585,1540,1503,1483,1461,1441,1329,1304,1259,1239,1219,1146,
1121,1039,954,859,831,817,800,789,762,703cm-1.
160.2,153.5(d,JC-F＝235.375Hz),143.8,133.7,130.4,130.0,126.9,119.9,118.6(d,JC-F＝9.125Hz),116.3(d,JC-F＝25.625Hz),113.7(d,JC-F＝27.75Hz),110.3,110.0,55.3.MS(ESI):243[M+H]+；HRMS(ESI)calcd for C14H12FN2O[M+H]+:243.0928；found:243.0963；IR(neat)ν1652,1599,1585,1540,1503,1483,1461,1441,1329,1304,1259,1239,1219,1146,
1121,1039,954,859,831,817,800,789,762,703cm-1.
[0081] 化合物3ae：棕色液体。1H NMR(500MHz,CDCl3,TMS)δ8.27(s,1H),7.72(s,1H),7.65(dd,J＝10.0,5.5Hz,1H),7.42(t,J＝7.5Hz,1H),7.35(d,J＝7.5Hz,2H),7.25(s,1H),7.12(t,J＝9.5Hz,1H),2.45(s,3H).13C NMR(125MHz,CDCl3)δ153.5(d,JC-F＝235.125Hz),143.7,139.2,133.6(d,JC-F＝1.875Hz),129.3(d,JC-F＝11.625Hz),128.7,128.5,127.2,
124.8,118.6(d,JC-F＝9.125Hz),116.2(d,JC-F＝25.625Hz),110.1(d,JC-F＝41.375Hz),
21.5.MS(ESI):227[M+H]+；HRMS(ESI)calcd for C14H12FN2[M+H]+:227.0979；found:
227.0997；IR(neat)ν1652,1604,1594,1503,1326,1306,1292,1253,1225,1197,1146,
1118,1101,948,852,816,788,757,699cm-1.
124.8,118.6(d,JC-F＝9.125Hz),116.2(d,JC-F＝25.625Hz),110.1(d,JC-F＝41.375Hz),
21.5.MS(ESI):227[M+H]+；HRMS(ESI)calcd for C14H12FN2[M+H]+:227.0979；found:
227.0997；IR(neat)ν1652,1604,1594,1503,1326,1306,1292,1253,1225,1197,1146,
1118,1101,948,852,816,788,757,699cm-1.
[0082] 化合物3af：棕色液体。1H NMR(500MHz,CDCl3,TMS)δ7.95-7.93(m,1H),7.77(s,1H),7.66(dd,J＝9.5,5.0Hz,1H),7.51-7.43(m,2H),7.31-7.24(m,2H),7.18-7.13(m,1H).13C NMR(125MHz,CDCl3)δ159.6(d,JC-F＝247.5Hz),153.3(d,JC-F＝235.25Hz),143.9,
134.9,130.9(d,JC-F＝3.125Hz),130.6(d,JC-F＝8.125Hz),124.8(d,JC-F＝3.625Hz),
121.4,118.3(d,JC-F＝9.125Hz),116.5(d,JC-F＝15.0Hz),116.34(d,JC-F＝25.625Hz),
116.27(d,JC-F＝21.25Hz),111.2(d,JC-F＝4.75Hz),110.9(d,JC-F＝4.875Hz).MS(ESI):231[M+H]+；HRMS(ESI)calcd for C13H9F2N2[M+H]+:231.0728；found:231.0736；IR(neat)ν
1652,1545,1529,1506,1467,1336,1299,1266,1229,1199,1159,1129,1084,950,867,842,
814,794,755cm-1.
134.9,130.9(d,JC-F＝3.125Hz),130.6(d,JC-F＝8.125Hz),124.8(d,JC-F＝3.625Hz),
121.4,118.3(d,JC-F＝9.125Hz),116.5(d,JC-F＝15.0Hz),116.34(d,JC-F＝25.625Hz),
116.27(d,JC-F＝21.25Hz),111.2(d,JC-F＝4.75Hz),110.9(d,JC-F＝4.875Hz).MS(ESI):231[M+H]+；HRMS(ESI)calcd for C13H9F2N2[M+H]+:231.0728；found:231.0736；IR(neat)ν
1652,1545,1529,1506,1467,1336,1299,1266,1229,1199,1159,1129,1084,950,867,842,
814,794,755cm-1.