CN112375102B - 一种可见光催化膦酰化咪唑并吡啶类化合物的制备方法 - Google Patents
一种可见光催化膦酰化咪唑并吡啶类化合物的制备方法 Download PDFInfo
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- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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Abstract
本发明公开了一种可见光催化下膦酰化咪唑并吡啶类化合物的制备方法。本发明以咪唑并吡啶类化合物和膦氧化物为原料，以罗丹明B为光催化剂，过氧化十二酰为氧化剂的作用下合成膦酰化咪唑并吡啶类化合物。该方法具有反应条件温和、操作简便、底物适用范围广等优点。该类类化合物在医药/有机合成等研究领域具有潜在的应用价值。
Description
技术领域
本发明涉及化学合成领域，具体涉及一种膦酰化咪唑并吡啶类化合物的制备方法。
背景技术
咪唑并吡啶类化合物具有独特的物理、化学及生物活性，广泛存在于生物活性分子及药物分子中，许多市售药物如唑吡坦、唑来咪啶、奥普利酮、阿吡培南，沙立哌定和米诺膦酸等均含有咪唑并吡啶骨架结构(J.Med.Chem.1998,41,4587；J.Org.Chem.2018,83,13991)。有机磷化合物在药物、活性分子、农药和功能材料等领域也具有非常重要的研究价值，但是，将磷取代基引入到咪唑并吡啶中的方法十分有限(Eur.J.Org.Chem.2015,2015,6526，Chem.Commun.2019,55,4230)，并且已开发的方法所能制备得到的产物结构类型有限，因而，开发步骤简便，快速高效合成膦酰化咪唑并吡啶类化合物的制备方法具有重要的研究意义与应用前景。
发明内容
本发明提出了一种膦酰化咪唑并吡啶类化合物的制备方法，该合成方法反应条件温和，简便安全，原料和催化剂价廉易得，是一种环境友好的绿色合成方法。
实现本发明的技术方案是：一种膦酰化咪唑并吡啶类化合物，其特征在于结构式如下：
其中R1为苯基、噻吩基、萘基；R2为苯基，对甲苯基、对氯苯基、乙氧基、3,5-二甲基苯基；其中R3为氨基、甲基、甲氧基、氟、氯、溴。
所述的膦酰化咪唑并吡啶类化合物的制备方法，其特征在于步骤如下：将咪唑并吡啶类化合物和膦氧化物溶解在碳酸二乙酯中，然后加入罗丹明B和过氧化十二酰(LPO)于白色LED的照射下搅拌8小时，反应结束后，经萃取，干燥，减压蒸去溶剂，经柱层析分离得到膦酰化咪唑并吡啶类化合物。
所述咪唑并吡啶类化合物的结构式如下：
其中R1为苯基、噻吩基、萘基；其中R3为氨基、甲基、甲氧基、氟、氯、溴。
所述溶剂为碳酸二乙酯。
所述咪唑并吡啶类化合物、膦氧化物、罗丹明B和过氧化十二酰(LPO)的摩尔比为1:2:0.05:2。
所述反应时间为8小时，所述光源为白光。
本发明所述制备方法的反应通式如下：
本发明的有益效果是：本发明提供了一种膦酰化咪唑并吡啶类化合物的制备方法，所述方法条件温和，催化剂廉价易得，操作简便、区域选择性高、产率高、有利于工业化生产，为膦酰化咪唑并吡啶类化合物的合成提供了新的方法。
具体实施方式
下面将结合本发明实施例，对本发明的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有付出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
实施例1
在8mL反应瓶中加入咪唑并吡啶(0.3mmol)，二苯基膦氧(0.6mmol)，LPO(0.6mmol)，罗丹明B(0.0015mmol)于2mL碳酸二乙酯中白光照射下搅拌8小时，薄层析检测反应过程。反应结束后，经萃取，干燥，减压蒸去溶剂，剩余物用硅胶柱层析分离(石油醚:乙酸乙酯＝1:1)，得终产物的产率为78％。
具体结果如下：
Yellow solid(92.2mg,78％)；Rf＝0.28(50％EtOAc in petroleum ether)；mp172.3-173.1℃；1H NMR(400MHz,CDCl3)δ8.76(d,J＝7.0Hz,1H),7.74(d,J＝9.0Hz,1H),7.55(dd,J＝12.8,7.0Hz,4H),7.45–7.34(m,3H),7.28(dd,J＝10.7,7.7Hz,4H),7.11(d,J＝8.3Hz,2H),7.05(s,1H),6.94(s,2H),6.81(s,1H)；13C{1H}NMR(101MHz,CDCl3)δ155.7(d,J＝13.3Hz),148.1(d,J＝10.3Hz),133.7,132.2(d,J＝2.8Hz),131.8(d,J＝10.6Hz),131.4(d,J＝112.1Hz),129.5,128.7,128.5,128.4,127.7(d,J＝3.6Hz),127.4,117.5,113.4,110.6(d,J＝123.1Hz)；31P NMR(162MHz,CDCl3)δ18.92；HRMS(ESI-TOF)m/z:[M+H]+Calcd for C25H20N2OP 395.1308,found:395.1306.
实施例2
在8mL反应瓶中加入2-(4-甲基苯基)咪唑并[1,2-a]吡啶(0.3mmol)，二苯基膦氧(0.6mmol)，LPO(0.6mmol)，罗丹明B(0.0015mmol)于2mL碳酸二乙酯中白光照射下搅拌8小时，薄层析检测反应过程。反应结束后，经萃取，干燥，减压蒸去溶剂，剩余物用硅胶柱层析分离(石油醚:乙酸乙酯＝1:1)，得终产物的产率为81％。
具体结果如下：
Faint yellow solid(99.2mg,81％)；Rf＝0.24(50％EtOAc in petroleumether)；mp192.3-193.8℃；1H NMR(400MHz,CDCl3)δ8.74(d,J＝7.0Hz,1H),7.72(d,J＝10.0Hz,1H),7.53(dd,J＝12.8,7.1Hz,4H),7.43–7.38(m,2H),7.37–7.32(m,1H),7.26(m,J＝7.7,3.1Hz,4H),6.99(d,J＝8.0Hz,2H),6.78(t,J＝6.9Hz,1H),6.72(d,J＝7.9Hz,2H),2.19(s,3H)；13C{1H}NMR(101MHz,CDCl3)δ155.9(d,J＝13.2Hz),148.1(d,J＝10.3Hz),137.4,132.0(d,J＝2.8Hz),131.8(d,J＝10.5Hz),131.5(d,J＝112.1Hz),130.7,129.4,128.6,128.3,128.0,127.6,117.5,113.3,110.5(d,J＝123.4Hz),21.2；31P NMR(162MHz,CDCl3)δ18.48；HRMS(ESI-TOF)m/z:[M+H]+Calcd for C26H22N2OP 409.1466,found:409.1468.
实施例3
在8mL反应瓶中加入2-(4-甲氧基苯基)咪唑并[1,2-a]吡啶(0.3mmol)，二苯基膦氧(0.6mmol)，LPO(0.6mmol)，罗丹明B(0.0015mmol)于2mL碳酸二乙酯中白光照射下搅拌8小时，薄层析检测反应过程。反应结束后，经萃取，干燥，减压蒸去溶剂，剩余物用硅胶柱层析分离(石油醚:乙酸乙酯＝1:1)，得终产物的产率为69％。
具体结果如下：
Yellow liquid(87.9mg,69％)；Rf＝0.19(50％EtOAc in petroleum ether)；1HNMR(400MHz,CDCl3)δ8.70(d,J＝6.9Hz,1H),7.72(d,J＝9.0Hz,1H),7.55(dd,J＝12.8,7.1Hz,4H),7.42(t,J＝7.4Hz,2H),7.37–7.32(m,1H),7.29(m,J＝7.6,3.2Hz,4H),7.06(d,J＝8.7Hz,2H),6.77(t,J＝7.3Hz,1H),6.47(d,J＝8.7Hz,2H),3.70(s,3H)；13C{1H}NMR(101MHz,CDCl3)δ159.2,155.6(d,J＝13.2Hz),148.1(d,J＝10.3Hz),132.1(d,J＝2.5Hz),131.8(d,J＝10.4Hz),131.5(d,J＝120.2Hz),130.8,128.6(d,J＝12.8Hz),128.3,127.6,126.1,117.4,113.2,112.9,110.3(d,J＝123.9Hz),55.2；31P NMR(162MHz,CDCl3)δ18.79.HRMS(ESI-TOF)m/z:[M+H]+Calcd for C26H22N2O2P425.1416,found:425.1418.
实施例4
在8mL反应瓶中加入2-(4-氰基苯基)咪唑并[1,2-a]吡啶(0.3mmol)，二苯基膦氧(0.6mmol)，LPO(0.6mmol)，罗丹明B(0.0015mmol)于2mL碳酸二乙酯中白光照射下搅拌8小时，薄层析检测反应过程。反应结束后，经萃取，干燥，减压蒸去溶剂，剩余物用硅胶柱层析分离(石油醚:乙酸乙酯＝1:1)，得终产物的产率为93％。
具体结果如下：
White solid(119.9mg,93％)；Rf＝0.31(50％EtOAc in petroleum ether)；mp178.0-178.6℃；1H NMR(400MHz,CDCl3)δ8.65(d,J＝7.0Hz,1H),7.75(d,J＝9.0Hz,1H),7.55(dd,J＝12.8,7.0Hz,4H),7.48(t,J＝7.5Hz,2H),7.44–7.39(m,1H),7.32(m,J＝7.7,3.2Hz,4H),7.26(s,4H),6.84(t,J＝6.9Hz,1H)；13C{1H}NMR(101MHz,CDCl3)δ153.4(d,J＝12.7Hz),148.2(d,J＝10.1Hz),138.6,132.6(d,J＝2.8Hz),131.8(d,J＝10.4Hz),130.98,130.95(d,J＝112.1Hz),130.2,128.9,128.8,128.3(d,J＝5.3Hz),118.6,117.7,113.9,111.8(d,J＝121.2Hz),,111.3；31P NMR(162MHz,CDCl3)δ17.56；HRMS(ESI-TOF)m/z:[M+H]+Calcd for C26H19N3OP 420.1262,found:420.1263.
实施例5
在8mL反应瓶中加入2-(4-三氟甲基苯基)咪唑并[1,2-a]吡啶(0.3mmol)，二苯基膦氧(0.6mmol)，LPO(0.6mmol)，罗丹明B(0.0015mmol)于2mL碳酸二乙酯中白光照射下搅拌8小时，薄层析检测反应过程。反应结束后，经萃取，干燥，减压蒸去溶剂，剩余物用硅胶柱层析分离(石油醚:乙酸乙酯＝1:1)，得终产物的产率为85％。
具体结果如下：
Orange solid(117.9mg,85％)；Rf＝0.29(50％EtOAc in petroleum ether)；mp201.9-202.3℃；1H NMR(400MHz,CDCl3)δ8.72(d,J＝6.9Hz,1H),7.75(d,J＝9.0Hz,1H),7.53(dd,J＝12.8,8.2Hz,4H),7.41(q,J＝10.3,9.0Hz,3H),7.28(m,J＝7.6,3.0Hz,4H),7.25–7.17(m,4H),6.83(t,J＝6.9Hz,1H)；13C{1H}NMR(101MHz,CDCl3)δ154.0(d,J＝12.9Hz),148.2(d,J＝10.1Hz),137.5,132.5(d,J＝2.8Hz),131.8(d,J＝10.4Hz),131.0(d,J＝112.1Hz),129.8,129.4,128.7(d,J＝12.7Hz),128.2(d,J＝24.5Hz),125.3,124.2(q,J＝3.7Hz),122.6,117.7,113.8,111.6(d,J＝121.5Hz)；31P NMR(162MHz,CDCl3)δ18.14；19F NMR(376MHz,CDCl3)δ-62.99；HRMS(ESI-TOF)m/z:[M+H]+Calcd for C26H19F3N2OP463.1184,found:463.1182.
实施例6
在8mL反应瓶中加入2-(4-氟基苯基)咪唑并[1,2-a]吡啶(0.3mmol)，二苯基膦氧(0.6mmol)，LPO(0.6mmol)，罗丹明B(0.0015mmol)于2mL碳酸二乙酯中白光照射下搅拌8小时，薄层析检测反应过程。反应结束后，经萃取，干燥，减压蒸去溶剂，剩余物用硅胶柱层析分离(石油醚:乙酸乙酯＝1:1)，得终产物的产率为63％。
具体结果如下：
Pink solid(77.9mg,63％)；Rf＝0.23(50％EtOAc in petroleum ether)；mp132.3-132.9℃；1H NMR(400MHz,CDCl3)δ8.71(d,J＝7.0Hz,1H),7.73(d,J＝9.0Hz,1H),7.59–7.50(m,4H),7.48–7.42(m,2H),7.41–7.35(m,1H),7.30(m,J＝11.2,7.3,5.0Hz,4H),7.10(dd,J＝8.7,5.4Hz,2H),6.81(t,J＝7.5Hz,1H),6.64(t,J＝8.7Hz,2H)；13C{1H}NMR(101MHz,CDCl3)δ162.4(d,J＝247.3Hz),154.6(d,J＝13.2Hz),148.1(d,J＝10.2Hz),132.3(d,J＝2.9Hz),131.8(d,J＝10.7Hz),131.33(d,J＝112.1Hz),131.29(d,J＝8.4Hz),128.7(d,J＝12.5Hz),128.4,127.9,117.5,114.5,114.3,113.5,110.9(d,J＝122.9Hz)；31PNMR(162MHz,CDCl3)δ18.43；19F NMR(376MHz,CDCl3)δ-113.86；HRMS(ESI-TOF)m/z:[M+H]+Calcd for C25H19FN2OP413.1216,found:413.1217.
实施例7
在8mL反应瓶中加入2-(4-氯苯基)咪唑并[1,2-a]吡啶(0.3mmol)，二苯基膦氧(0.6mmol)，LPO(0.6mmol)，罗丹明B(0.0015mmol)于2mL碳酸二乙酯中白光照射下搅拌8小时，薄层析检测反应过程。反应结束后，经萃取，干燥，减压蒸去溶剂，剩余物用硅胶柱层析分离(石油醚:乙酸乙酯＝1:1)，得终产物的产率为72％。
具体结果如下：
Pink solid(92.6mg,72％)；Rf＝0.26(50％EtOAc in petroleum ether)；mp186,2-187,5℃；1H NMR(400MHz,CDCl3)δ8.71(d,J＝6.9Hz,1H),7.73(d,J＝9.9Hz,1H),7.58–7.50(m,4H),7.49–7.43(m,2H),7.38(dd,J＝9.0,5.9Hz,1H),7.30(m,J＝7.7,2.9Hz,4H),7.04(d,J＝8.4Hz,2H),6.91(d,J＝8.4Hz,2H),6.84–6.78(m,1H)；13C{1H}NMR(101MHz,CDCl3)δ154.4(d,J＝12.9Hz),148.2(d,J＝10.2Hz),134.0,132.3(d,J＝2.8Hz),131.8(d,J＝10.4Hz),131.2(d,J＝112.1Hz),130.8,128.8,128.6,128.3,127.9,127.5,117.6,113.6,111.1(d,J＝122.4Hz)；31P NMR(162MHz,CDCl3)δ18.36；HRMS(ESI-TOF)m/z:[M+H]+Calcd for C25H19ClN2OP 429.0918,found:429.0917.
实施例8
在8mL反应瓶中加入2-(4-溴苯基)咪唑并[1,2-a]吡啶(0.3mmol)，二苯基膦氧(0.6mmol)，LPO(0.6mmol)，罗丹明B(0.0015mmol)于2mL碳酸二乙酯中白光照射下搅拌8小时，薄层析检测反应过程。反应结束后，经萃取，干燥，减压蒸去溶剂，剩余物用硅胶柱层析分离(石油醚:乙酸乙酯＝1:1)，得终产物的产率为85％。
具体结果如下：
White solid(120.3mg,85％)；Rf＝0.28(50％EtOAc in petroleum ether)；mp211.4-212.1℃；1H NMR(400MHz,CDCl3)δ8.70(d,J＝7.0Hz,1H),7.73(d,J＝8.0Hz,1H),7.58–7.50(m,4H),7.51–7.42(m,2H),7.42–7.33(m,1H),7.30(m,J＝7.7,3.2Hz,4H),7.06(d,J＝8.4Hz,2H),6.97(d,J＝8.4Hz,2H),6.85–6.77(m,1H)；13C{1H}NMR(101MHz,CDCl3)δ154.4(d,J＝12.8Hz),148.2(d,J＝10.1Hz),132.7,132.3(d,J＝2.8Hz),131.8(d,J＝10.5Hz),131.2(d,J＝113.1Hz),131.0,130.5,128.7(d,J＝12.8Hz),128.4,127.9,122.3,117.6,113.6,111.1(d,J＝122.2Hz)；31P NMR(162MHz,CDCl3)δ18.38；HRMS(ESI-TOF)m/z:[M+H]+Calcd for C25H19BrN2OP473.0415,found:473.0413.
实施例9
在8mL反应瓶中加入2-(3-氯苯基)咪唑并[1,2-a]吡啶(0.3mmol)，二苯基膦氧(0.6mmol)，LPO(0.6mmol)，罗丹明B(0.0015mmol)于2mL碳酸二乙酯中白光照射下搅拌8小时，薄层析检测反应过程。反应结束后，经萃取，干燥，减压蒸去溶剂，剩余物用硅胶柱层析分离(石油醚:乙酸乙酯＝1:1)，得终产物的产率为70％。
具体结果如下：
Orange solid(90.0mg,70％)；Rf＝0.25(50％EtOAc in petroleum ether)；mp167.2-168.5℃；1H NMR(400MHz,CDCl3)δ8.73(d,J＝6.9Hz,1H),7.74(d,J＝9.0Hz,1H),7.55(dd,J＝12.8,7.2Hz,4H),7.46–7.41(m,2H),7.38(d,J＝8.6Hz,1H),7.32(m,J＝7.6,3.1Hz,4H),7.08–7.00(m,3H),6.91(t,J＝8.1Hz,1H),6.83(t,J＝6.9Hz,1H)；13C{1H}NMR(101MHz,CDCl3)δ154.0(d,J＝13.0Hz),148.1(d,J＝10.0Hz),135.6,133.2,132.5(d,J＝2.0Hz),131.7(d,J＝10.5Hz),131.0(d,J＝113.1Hz),129.8,128.8,128.7,128.6,128.4,128.0(d,J＝2.8Hz),127.7,117.6,113.7,111.1(d,J＝122.3Hz)；31P NMR(162MHz,CDCl3)δ18.54；HRMS(ESI-TOF)m/z:[M+H]+Calcd for C25H19ClN2OP 429.0918,found:429.0920.
实施例10
在8mL反应瓶中加入2-(2,4-二甲基苯基)咪唑并[1,2-a]吡啶(0.3mmol)，二苯基膦氧(0.6mmol)，LPO(0.6mmol)，罗丹明B(0.0015mmol)于2mL碳酸二乙酯中白光照射下搅拌8小时，薄层析检测反应过程。反应结束后，经萃取，干燥，减压蒸去溶剂，剩余物用硅胶柱层析分离(石油醚:乙酸乙酯＝1:1)，得终产物的产率为61％。
具体结果如下：
Yellow liquid(77.2mg,61％)；Rf＝0.33(50％EtOAc in petroleum ether)；1HNMR(400MHz,CDCl3)δ8.91(d,J＝6.9Hz,1H),7.71(d,J＝9.0Hz,1H),7.42(m,J＝31.5,15.7,8.7Hz,7H),7.27–7.21(m,4H),6.85(t,J＝6.8Hz,1H),6.72(d,J＝7.5Hz,1H),6.56(d,J＝11.0Hz,2H),2.17(s,3H),1.91(s,3H)；13C{1H}NMR(101MHz,CDCl3)δ155.0(d,J＝14.1Hz),148.1(d,J＝10.2Hz),137.7,136.4,131.9(d,J＝2.8Hz),131.7(d,J＝10.6Hz),131.3(d,J＝112.1Hz),130.4,130.3,130.2,128.3(d,J＝3.3Hz),128.2,127.4,125.4,117.5,113.4,111.2(d,J＝124.7Hz),21.0,20.0；31P NMR(162MHz,CDCl3)δ19.65；HRMS(ESI-TOF)m/z:[M+H]+Calcd for C27H24N2OP 423.1623,found:423.1626.
实施例11
在8mL反应瓶中加入2-(奈-2-基)咪唑并[1,2-a]吡啶(0.3mmol)，二苯基膦氧(0.6mmol)，LPO(0.6mmol)，罗丹明B(0.0015mmol)于2mL碳酸二乙酯中白光照射下搅拌8小时，薄层析检测反应过程。反应结束后，经萃取，干燥，减压蒸去溶剂，剩余物用硅胶柱层析分离(石油醚:乙酸乙酯＝1:1)，得终产物的产率为79％。
具体结果如下：
Orange solid(105.3mg,79％)；Rf＝0.31(50％EtOAc in petroleum ether)；mp201.2-201.9℃；1H NMR(400MHz,CDCl3)δ8.79(d,J＝6.9Hz,1H),7.77(d,J＝8.9Hz,1H),7.67(d,J＝7.9Hz,1H),7.58–7.51(m,6H),7.46(d,J＝8.4Hz,1H),7.41–7.35(m,3H),7.34–7.30(m,1H),7.22–7.17(m,2H),7.14(m,J＝6.6,3.3Hz,4H),6.82(t,J＝6.9Hz,1H)；13C{1H}NMR(101MHz,CDCl3)δ155.6(d,J＝13.1Hz),148.2(d,J＝10.2Hz),132.6,132.2,132.0(d,J＝2.9Hz),131.7(d,J＝10.4Hz),131.4(d,J＝113.1Hz),131.1,129.7,128.5(d,J＝12.8Hz),128.5,128.2,127.8,127.4,127.1,126.8,126.2,125.7,117.6,113.4,111.1(d,J＝122.9Hz)；31P NMR(162MHz,CDCl3)δ18.90；HRMS(ESI-TOF)m/z:[M+H]+Calcd forC29H22N2OP 445.1466,found:445.1463.
实施例12
在8mL反应瓶中加入2-(噻吩-2-基)咪唑并[1,2-a]吡啶(0.3mmol)，二苯基膦氧(0.6mmol)，LPO(0.6mmol)，罗丹明B(0.0015mmol)于2mL碳酸二乙酯中白光照射下搅拌8小时，薄层析检测反应过程。反应结束后，经萃取，干燥，减压蒸去溶剂，剩余物用硅胶柱层析分离(石油醚:乙酸乙酯＝1:1)，得终产物的产率为71％。
具体结果如下：
White solid(85.3mg,71％)；Rf＝0.34(50％EtOAc in petroleum ether)；mp194.6-195.7℃；1H NMR(400MHz,CDCl3)δ8.89(d,J＝7.0Hz,1H),7.75–7.70(m,1H),7.68–7.60(m,4H),7.50–7.44(m,2H),7.40–7.33(m,5H),7.13(dd,J＝5.0,1.0Hz,1H),6.81(s,1H),6.54–6.46(m,2H).；13C{1H}NMR(101MHz,CDCl3)δ148.5(d,J＝12.7Hz),148.2(d,J＝10.1Hz),135.0,132.4(d,J＝2.8Hz),131.8(d,J＝10.6Hz),131.5(d,J＝113.1Hz),129.1,128.7(d,J＝12.9Hz),128.5,127.9,127.1,126.8,117.4,113.4,110.4(d,J＝122.5Hz)；31PNMR(162MHz,CDCl3δ19.85；HRMS(ESI-TOF)m/z:[M+H]+Calcd for C23H18N2OPS 401.0874,found:401.0876.
实施例13
在8mL反应瓶中加入2-苯基咪唑并[1,2-a]吡啶-8-胺(0.3mmol)，二苯基膦氧(0.6mmol)，LPO(0.6mmol)，罗丹明B(0.0015mmol)于2mL碳酸二乙酯中白光照射下搅拌8小时，薄层析检测反应过程。反应结束后，经萃取，干燥，减压蒸去溶剂，剩余物用硅胶柱层析分离(石油醚:乙酸乙酯＝1:1)，得终产物的产率为68％。
具体结果如下。
Orange solid(83.5mg,68％)；Rf＝0.28(50％EtOAc in petroleum ether)；mp150.1-151.6℃；1H NMR(400MHz,(CD3)2SO))δ8.22(s,1H),7.80(d,J＝6.7Hz,2H),7.73–7.56(m,10H),7.40(s,2H),7.30(d,J＝7.1Hz,1H),6.54(d,J＝10.5Hz,3H),6.29(d,J＝6.5Hz,1H)；13C{1H}NMR(101MHz,(CD3)2SO)δ143.4,141.3(d,J＝1.5Hz),139.1(d,J＝4.5Hz),133.8,133.1(d,J＝2.4Hz),132.1(d,J＝10.1Hz),131.0(d,J＝108.1Hz),129.6(d,J＝12.2Hz),129.2,128.2,125.8,125.4,115.5(d,J＝122.5Hz),110.4,99.5(d,J＝11.6Hz)；31P NMR(162MHz,(CD3)2SO)δ22.04；HRMS(ESI-TOF)m/z:[M+H]+Calcd forC25H21N3OP 410.1419,found:410.1417.
实施例14
在8mL反应瓶中加入7-甲基-2-苯基咪唑并[1,2-a]吡啶(0.3mmol)，二苯基膦氧(0.6mmol)，LPO(0.6mmol)，罗丹明B(0.0015mmol)于2mL碳酸二乙酯中白光照射下搅拌8小时，薄层析检测反应过程。反应结束后，经萃取，干燥，减压蒸去溶剂，剩余物用硅胶柱层析分离(石油醚:乙酸乙酯＝1:1)，得终产物的产率为68％。
具体结果如下。
Orange solid(101.7mg,83％)；Rf＝0.25(50％EtOAc in petroleum ether)；mp214.3-215.6℃；1H NMR(400MHz,CDCl3)δ8.59(d,J＝7.1Hz,1H),7.54(dd,J＝12.8,7.1Hz,4H),7.49(s,1H),7.40(t,J＝7.0Hz,2H),7.26(m,J＝7.6,3.0Hz,4H),7.10(d,J＝8.3Hz,2H),7.04(t,J＝7.4Hz,1H),6.93(t,J＝7.6Hz,2H),6.63(d,J＝8.5Hz,1H),2.41(s,3H)；13C{1H}NMR(101MHz,CDCl3)δ155.8(d,J＝13.3Hz),148.6(d,J＝10.2Hz),139.0,133.8,132.1(d,J＝2.9Hz),131.8(d,J＝10.4Hz),131.5(d,J＝113.1Hz),129.5,128.5(d,J＝12.8Hz),127.7,127.4,127.3,116.0,115.9,109.9(d,J＝124.6Hz),21.4；31P NMR(162MHz,CDCl3)δ18.74；HRMS(ESI-TOF)m/z:[M+H]+Calcd for C26H22N2OP 409.1466,found:409.1468.
实施例15
在8mL反应瓶中加入7-甲氧基-2-苯基咪唑并[1,2-a]吡啶(0.3mmol)，二苯基膦氧(0.6mmol)，LPO(0.6mmol)，罗丹明B(0.0015mmol)于2mL碳酸二乙酯中白光照射下搅拌8小时，薄层析检测反应过程。反应结束后，经萃取，干燥，减压蒸去溶剂，剩余物用硅胶柱层析分离(石油醚:乙酸乙酯＝1:1)，得终产物的产率为68％。
具体结果如下。
Orange solid(112.0mg,88％)；Rf＝0.26(50％EtOAc in petroleum ether)；mp219.7-220.2℃；1H NMR(400MHz,CDCl3)δ8.54(d,J＝7.5Hz,1H),7.55(dd,J＝12.3,7.7Hz,4H),7.38(t,J＝6.8Hz,2H),7.26(s,4H),7.11(d,J＝7.2Hz,2H),7.02(dd,J＝15.2,7.8Hz,2H),6.92(t,J＝7.2Hz,2H),6.49(d,J＝6.0Hz,1H),3.84(s,3H)；13C{1H}NMR(101MHz,CDCl3)δ159.8,156.0(d,J＝13.2Hz),150.0(d,J＝10.0Hz),133.8,132.1(d,J＝2.9Hz),131.8(d,J＝10.4Hz),131.6(d,J＝111.1Hz),129.4,128.6,128.5(d,J＝12.8Hz),127.6,127.3,109.3(d,J＝125.3Hz),107.9,95.0,55.6；31P NMR(162MHz,CDCl3)δ18.61；HRMS(ESI-TOF)m/z:[M+H]+Calcd for C26H22N2O2P 425.1416,found:425.1418.
实施例16
在8mL反应瓶中加入7-氟-2-苯基咪唑并[1,2-a]吡啶(0.3mmol)，二苯基膦氧(0.6mmol)，LPO(0.6mmol)，罗丹明B(0.0015mmol)于2mL碳酸二乙酯中白光照射下搅拌8小时，薄层析检测反应过程。反应结束后，经萃取，干燥，减压蒸去溶剂，剩余物用硅胶柱层析分离(石油醚:乙酸乙酯＝1:1)，得终产物的产率为85％。
具体结果如下。
Orange solid(105.2mg,85％)；Rf＝0.29(50％EtOAc in petroleum ether)；mp176.8-177.4℃；1H NMR(400MHz,CDCl3)δ8.86–8.79(m,1H),7.53(dd,J＝12.6,7.8Hz,4H),7.42(t,J＝7.1Hz,2H),7.35(d,J＝8.7Hz,1H),7.31–7.25(m,4H),7.07(t,J＝9.0Hz,3H),6.94(t,J＝7.4Hz,2H),6.69(t,J＝7.2Hz,1H)；13C{1H}NMR(101MHz,CDCl3)δ161.9(d,J＝255.8Hz),156.7(d,J＝13.0Hz),148.9(dd,J＝13.9,10.1Hz),133.4,132.4(d,J＝2.8Hz),131.8(d,J＝10.5Hz),131.2(d,J＝113.1Hz),130.1(d,J＝10.8Hz),129.4,128.6(d,J＝12.9Hz),127.9,127.4,110.5(d,J＝122.8Hz),105.6(d,J＝28.4Hz),101.4(d,J＝23.4Hz)；31P NMR(162MHz,CDCl3)δ17.51；19F NMR(376MHz,CDCl3)δ108.73；HRMS(ESI-TOF)m/z:[M+H]+Calcd for C25H19FN2OP 413.1216,found:413.1215.
实施例17
在8mL反应瓶中加入7-氯-2-苯基咪唑并[1,2-a]吡啶(0.3mmol)，二苯基膦氧(0.6mmol)，LPO(0.6mmol)，罗丹明B(0.0015mmol)于2mL碳酸二乙酯中白光照射下搅拌8小时，薄层析检测反应过程。反应结束后，经萃取，干燥，减压蒸去溶剂，剩余物用硅胶柱层析分离(石油醚:乙酸乙酯＝1:1)，得终产物的产率为80％。
具体结果如下。
Yellow solid(102.9mg,80％)；Rf＝0.28(50％EtOAc in petroleum ether)；mp190.0-191.2℃；1H NMR(400MHz,CDCl3)δ8.77(d,J＝7.4Hz,1H),7.72(s,1H),7.53(dd,J＝12.8,7.3Hz,4H),7.42(t,J＝7.0Hz,2H),7.29(m,J＝8.9,4.5Hz,4H),7.07(t,J＝8.2Hz,3H),6.94(t,J＝7.6Hz,2H),6.80(d,J＝7.4Hz,1H)；13C{1H}NMR(101MHz,CDCl3)δ156.3(d,J＝12.9Hz),148.0(d,J＝10.1Hz),134.5,133.3,132.4(d,J＝2.8Hz),131.8(d,J＝10.5Hz),131.1(d,J＝113.1Hz),129.4,128.7,128.6,128.0,127.5,116.4,114.9,111.0(d,J＝121.5Hz)；31PNMR(162MHz,CDCl3)δ17.51；HRMS(ESI-TOF)m/z:[M+H]+Calcd forC25H19ClN2OP 429.0918,found:429.0917.
实施例18
在8mL反应瓶中加入7-溴-2-苯基咪唑并[1,2-a]吡啶(0.3mmol)，二苯基膦氧(0.6mmol)，LPO(0.6mmol)，罗丹明B(0.0015mmol)于2mL碳酸二乙酯中白光照射下搅拌8小时，薄层析检测反应过程。反应结束后，经萃取，干燥，减压蒸去溶剂，剩余物用硅胶柱层析分离(石油醚:乙酸乙酯＝1:1)，得终产物的产率为67％。
具体结果如下：
White solid(95.1mg,67％)；Rf＝0.29(50％EtOAc in petroleum ether)；mp215.8-216.3℃；1H NMR(400MHz,CDCl3)δ8.70(d,J＝7.4Hz,1H),7.91(s,1H),7.53(dd,J＝12.9,7.2Hz,4H),7.46–7.40(m,2H),7.28(m,J＝7.7,3.1Hz,4H),7.07(t,J＝8.2Hz,3H),6.97–6.88(m,3H)；13C{1H}NMR(101MHz,CDCl3)δ156.2(d,J＝13.0Hz),148.3(d,J＝10.1Hz),133.2,132.4(d,J＝2.8Hz),131.8(d,J＝10.5Hz),131.1(d,J＝113.1Hz),129.5,128.7(d,J＝12.9Hz),128.6,128.0,127.5,122.0,119.8,117.3,111.1(d,J＝121.2Hz)；31PNMR(162MHz,CDCl3)δ19.29；HRMS(ESI-TOF)m/z:[M+H]+Calcd for C25H19BrN2OP 473.0415,found:473.0414.
实施例19
在8mL反应瓶中加入2-苯基苯并[d]咪唑并[2,1,b]噻唑(0.3mmol)，二苯基膦氧(0.6mmol)，LPO(0.6mmol)，罗丹明B(0.0015mmol)于2mL碳酸二乙酯中白光照射下搅拌8小时，薄层析检测反应过程。反应结束后，经萃取，干燥，减压蒸去溶剂，剩余物用硅胶柱层析分离(石油醚:乙酸乙酯＝1:1)，得终产物的产率为74％。
具体结果如下：
Orange solid(100.0mg,74％)；Rf＝0.32(50％EtOAc in petroleum ether)；mp165.2-165.7℃；1H NMR(400MHz,CDCl3δ8.50–8.45(m,1H),7.66–7.61(m,1H),7.58–7.52(m,4H),7.36–7.31(m,2H),7.23(m,J＝10.6,7.5,3.5Hz,6H),7.10–7.06(m,2H),7.01(t,J＝7.4Hz,1H),6.91(t,J＝7.5Hz,2H)；13C{1H}NMR(101MHz,CDCl3)δ158.2(d,J＝14.1Hz),153.0(d,J＝10.7Hz),133.6,133.3,132.3,132.1(d,J＝2.9Hz),131.9(d,J＝10.3Hz),130.4(d,J＝144.4Hz),129.6,128.5(d,J＝12.9Hz),127.7,127.4,126.4,125.1,123.6,117.5,115.6(d,J＝120.5Hz)；31P NMR(162MHz,CDCl3)δ18.26；HRMS(ESI-TOF)m/z:[M+H]+Calcd for C27H20N2OPS 451.1031,found:451.1030.
实施例20
在8mL反应瓶中加入2-(4-甲基苯基)咪唑并[1,2-a]吡啶(0.3mmol)，二(4-甲氧基苯基)膦氧(0.6mmol)，LPO(0.6mmol)，罗丹明B(0.0015mmol)于2mL碳酸二乙酯中白光照射下搅拌8小时，薄层析检测反应过程。反应结束后，经萃取，干燥，减压蒸去溶剂，剩余物用硅胶柱层析分离(石油醚:乙酸乙酯＝1:1)，得终产物的产率为72％。
具体结果如下：
Orange liquid(101.2mg,72％)；Rf＝0.34(50％EtOAc in petroleum ether)；1HNMR(400MHz,CDCl3)δ8.78(d,J＝7.0Hz,1H),7.70(d,J＝9.9Hz,1H),7.42(dd,J＝12.3,8.8Hz,4H),7.38–7.31(m,1H),6.95(d,J＝8.0Hz,2H),6.77(m,J＝8.7,1.5Hz,7H),3.78(s,6H),2.23(s,3H)；13C{1H}NMR(101MHz,CDCl3)δ162.7(d,J＝2.9Hz),155.5(d,J＝13.2Hz),147.9(d,J＝10.2Hz),137.0,133.7(d,J＝11.9Hz),131.0,129.5,127.9(d,J＝101.0Hz),127.9,123.4,122.2,117.4,114.1(d,J＝13.9Hz),113.2,111.5(d,J＝123.6Hz),55.2(d,J＝2.9Hz),21.1；31P NMR(162MHz,CDCl3)δ19.02；HRMS(ESI-TOF)m/z:[M+H]+Calcd forC28H26N2O3P 469.1676,found:469.1675.
实施例21
在8mL反应瓶中加入2-(4-甲基苯基)咪唑并[1,2-a]吡啶(0.3mmol)，二(4-甲基苯基)膦氧(0.6mmol)，LPO(0.6mmol)，罗丹明B(0.0015mmol)于2mL碳酸二乙酯中白光照射下搅拌8小时，薄层析检测反应过程。反应结束后，经萃取，干燥，减压蒸去溶剂，剩余物用硅胶柱层析分离(石油醚:乙酸乙酯＝1:1)，得终产物的产率为64％。
具体结果如下：
Orange liquid(83.8mg,64％)；Rf＝0.38(50％EtOAc in petroleum ether)；1HNMR(400MHz,CDCl3)δ8.75(d,J＝7.0Hz,1H),7.71(d,J＝9.9Hz,1H),7.39(dd,J＝12.6,8.0Hz,5H),7.06(dd,J＝7.9,2.5Hz,4H),6.94(d,J＝8.0Hz,2H),6.79(t,J＝6.9Hz,1H),6.73(d,J＝7.8Hz,2H),2.33(s,6H),2.23(s,3H)；13C{1H}NMR(101MHz,CDCl3)δ155.6(d,J＝13.0Hz),148.0(d,J＝10.1Hz),142.7(d,J＝2.8Hz),137.2,131.8(d,J＝10.8Hz),131.0,129.4,129.2(d,J＝13.3Hz),128.4,128.2(d,J＝114.1Hz),127.9,127.5,117.4,113.2,111.1(d,J＝122.9Hz),21.6(d,J＝7.1Hz),21.1；31P NMR(162MHz,CDCl3)δ19.39；HRMS(ESI-TOF)m/z:[M+H]+Calcd for C28H26N2OP 437.1779,found:437.1775.
实施例22
在8mL反应瓶中加入2-(4-甲基苯基)咪唑并[1,2-a]吡啶(0.3mmol)，二(4-氯苯基)膦氧(0.6mmol)，LPO(0.6mmol)，罗丹明B(0.0015mmol)于2mL碳酸二乙酯中白光照射下搅拌8小时，薄层析检测反应过程。反应结束后，经萃取，干燥，减压蒸去溶剂，剩余物用硅胶柱层析分离(石油醚:乙酸乙酯＝1:1)，得终产物的产率为83％。
具体结果如下：
Yellow solid(118.8mg,83％)；Rf＝0.37(50％EtOAc in petroleum ether)；mp113.2-114.5℃；1H NMR(400MHz,CDCl3)δ8.67(d,J＝6.9Hz,1H),7.74(d,J＝9.0Hz,1H),7.41(dd,J＝12.3,8.5Hz,5H),7.27–7.22(m,4H),6.93(d,J＝8.0Hz,2H),6.82(dd,J＝12.4,7.4Hz,3H),2.29(s,3H)；13C{1H}NMR(101MHz,CDCl3)δ156.2(d,J＝13.5Hz),148.2(d,J＝10.3Hz),139.2(d,J＝3.6Hz),138.2,133.1(d,J＝11.4Hz),130.5,129.5(d,J＝114.1Hz),129.3,129.0,128.9,128.2,128.0(d,J＝8.5Hz),117.7,113.7,109.9(d,J＝126.8Hz),21.2；31P NMR(162MHz,CDCl3)δ19.39；HRMS(ESI-TOF)m/z:[M+H]+Calcd forC26H20Cl2N2OP 477.0687,found:477.0688.
实施例23
在8mL反应瓶中加入2-(4-甲基苯基)咪唑并[1,2-a]吡啶(0.3mmol)，二(3,4-二甲基苯基)膦氧(0.6mmol)，LPO(0.6mmol)，罗丹明B(0.0015mmol)于2mL碳酸二乙酯中白光照射下搅拌8小时，薄层析检测反应过程。反应结束后，经萃取，干燥，减压蒸去溶剂，剩余物用硅胶柱层析分离(石油醚:乙酸乙酯＝1:1)，得终产物的产率为85％。
具体结果如下：
Orange solid(118.4mg,85％)；Rf＝0.33(50％EtOAc in petroleum ether)；mp99.3-99.6℃；1H NMR(400MHz,CDCl3)δ8.80–8.75(m,1H),7.71(d,J＝9.0Hz,1H),7.37–7.31(m,1H),7.12(d,J＝13.1Hz,4H),7.04–6.96(m,4H),6.77(dd,J＝16.6,7.9Hz,3H),2.22(s,3H),2.19(s,12H)；13C{1H}NMR(101MHz,CDCl3)155.6(d,J＝13.1Hz),148.0(d,J＝10.0Hz),138.2(d,J＝13.5Hz),137.2,133.7(d,J＝2.9Hz),131.2(d,J＝111.1Hz),131.1,129.5(d,J＝10.4Hz),129.2,128.5,127.6,127.4,117.4,113.1,111.1(d,J＝121.8Hz),21.2,21.1；31P NMR(162MHz,CDCl3)δ19.85；HRMS(ESI-TOF)m/z:[M+H]+Calcd for C30H30N2OP465.2093,found:465.2092.
实施例24
在8mL反应瓶中加入2-(4-甲基苯基)咪唑并[1,2-a]吡啶(0.3mmol)，亚磷酸二乙酯(0.6mmol)，LPO(0.6mmol)，罗丹明B(0.0015mmol)于2mL碳酸二乙酯中白光照射下搅拌8小时，薄层析检测反应过程。反应结束后，经萃取，干燥，减压蒸去溶剂，剩余物用硅胶柱层析分离(石油醚:乙酸乙酯＝1:1)，得终产物的产率为72％。
具体结果如下：
Faint yellow liquid(44.4mg,43％)；Rf＝0.39(50％EtOAc in petroleumether)；1H NMR(400MHz,CDCl3)δ9.19(d,J＝7.0Hz,1H),7.75(dd,J＝16.0,8.6Hz,3H),7.42–7.35(m,1H),7.26(s,1H),7.24(s,1H),6.94(t,J＝7.5Hz,1H),4.11(m,J＝10.0,7.2Hz,2H),3.97–3.86(m,2H),2.41(s,3H),1.16(t,J＝7.0Hz,6H)；13C{1H}NMR(101MHz,CDCl3)δ155.2(d,J＝17.7Hz),148.2(d,J＝14.5Hz),138.7,130.7,129.6,128.6,128.4,127.4,117.3,113.4,107.0(d,J＝226.4Hz),62.4(d,J＝5.0Hz),21.4,15.9(d,J＝7.2Hz)；31P NMR(162MHz,CDCl3)δ8.39；HRMS(ESI-TOF)m/z:[M+H]+Calcd for C18H22N2O3P345.1362,found:345.1366.
以上所述仅为本发明的较佳实施例而已，并不用以限制本发明，凡在本发明的精神和原则之内，所作的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。
Claims (2)
1.一种膦酰化咪唑并吡啶类化合物的制备方法，其特征在于：所述制备的膦酰化咪唑并吡啶类化合物结构式如下：
其中，R1为苯基、噻吩基、萘基；R2为苯基、对甲苯基、对氯苯基、乙氧基、3,5-二甲基苯基；其中R3为氨基、甲基、甲氧基、氟、氯、溴；
所述制备方法的反应通式如下：
2.根据权利要求1所述的膦酰化咪唑并吡啶类化合物的制备方法，其特征在于：所述咪唑并吡啶类化合物
膦氧化物
罗丹明B和过氧化十二酰的摩尔比为1:2:0.05:2。
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