CN109734713A - 一种3-亚胺基咪唑并[1,2-a]吡啶化合物 - Google Patents
一种3-亚胺基咪唑并[1,2-a]吡啶化合物 Download PDFInfo
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Abstract
本发明公开了一种可见光催化N‑芳基甘氨酸酯与咪唑并[1,2‑a]吡啶化合物的氧化交叉偶联反应制备3‑亚胺基咪唑并[1,2‑a]吡啶化合物。在本发明方法中,曙红Y为光敏剂,柠檬酸为添加剂,N‑芳基甘氨酸酯与咪唑并[1,2‑a]吡啶化合物在有机溶剂中室温下经可见光照射后,直接脱氢交叉偶联生成3‑亚胺基咪唑并[1,2‑a]吡啶化合物。本发明方法以曙红Y作光敏剂,一水柠檬酸为添加剂,乙醇作溶剂,室温下空气氛围中利用可见光催化有效制备了一种3‑亚胺基咪唑并[1,2‑a]吡啶化合物。本发明方法操作简便,反应条件温和,选择性好,原子经济性。
Description
技术领域
本发明属于有机化学领域,涉及咪唑并[1,2-a]吡啶化合物的合成,特别涉及一种3-亚胺基咪唑并[1,2-a]吡啶化合物的合成方法。
背景技术
咪唑并[1,2-a]吡啶是一类重要的芳香类含氮杂环化合物,在医药、农药和材料科学领域具有非常广泛的应用。该类化合物因其特定的生理活性和化学活性受到化学家们极大的关注。许多咪唑并[1,2-a]吡啶化合物具有抗菌、抗病毒、抗焦虑活性,可用作治疗肿瘤、高血压、糖尿病和精神病等的处方药,也可用作治疗白血病、肝炎等的备用药物。例如,C3位取代的咪唑并[1,2-a]吡啶结构存在于一些重要的药物分子如唑吡坦、阿吡旦、沙立吡旦、奈可吡旦中,并且咪唑并[1,2-a]吡啶C3位不同的取代基能够极大影响其药物活性。因此,简便高效合成C3官能团化的咪唑并[1,2-a]吡啶化合物引起了化学家们广泛的研究兴趣。近年来,大量C3位官能团化的咪唑并[1,2-a]吡啶化合物及其合成方法被广泛报道。然而,到目前为止,利用绿色清洁并且可持续的可见光催化N-芳基甘胺酸酯与咪唑并[1,2-a]吡啶化合物合成3-亚胺基咪唑并[1,2-a]吡啶化合物未见文献和专利报道。
发明内容
本发明提供一种可见光催化合成3-亚胺基咪唑并[1,2-a]吡啶化合物的有效方法。该方法以曙红Y为光催化剂,柠檬酸为添加剂,咪唑并[1,2-a]吡啶化合物和N-芳基甘氨酸酯为反应底物,空气中室温条件下,通过可见光催化一步合成3-亚胺基咪唑并[1,2-a]吡啶化合物。本发明提供的一种3-亚胺基咪唑并[1,2-a]吡啶化合物的绿色合成方法,其操作过程简单、反应条件温和、原子经济并且对环境友好,具有较大应用前景。
本发明采用如下技术方案:一种3-亚胺基咪唑并[1,2-a]吡啶化合物,其结构式如式(I)所示:
其中,R1为氢、供电子基团或吸电子基团,优选的,所述供电子基团可以是非限定性地,例如可为甲基或甲氧基;所述吸电子基团可以是卤素,非限定性地例如可为氯。
R2为烷基或苄基,优选的,所述烷基可以是非限定性地,例如可为甲基、乙基、异丙基或者叔丁基。
R3与吡啶环相连接,可以是氢、供电子基团,优选的,所述的供电子基团为甲基。
R4为烷基、芳基或取代的芳基,优选的,所述烷基可以是非限定性地,例如可为甲基,所述的芳基为苯基,所述取代的芳基为3,4-二甲氧基苯基、4-甲氧基苯基、4-甲苯基、4-氟苯基、4-氯苯基、4-溴苯基。
本发明一种3-亚胺基咪唑并[1,2-a]吡啶化合物的制备方法,包括以下实验步骤:LED蓝光照射下,以曙红Y为光催化剂,一水柠檬酸为添加剂,N-芳基甘氨酸酯(II)和咪唑并[1,2-a]吡啶化合物(III)在有机溶剂中,空气氛围下26℃搅拌反应12-18小时,至TLC检测反应完全,反应液浓缩后用乙酸乙酯/石油醚硅胶柱层析分离,可制得产物3-亚胺基咪唑并[1,2-a]吡啶化合物,反应通式如下:
在本发明所述的制备方法中,光敏剂可以是Ru(bpy3)Cl2·6H2O、Eosin B、EosinY、Ir(bpy)3,Acr+-Mes-ClO4 -优选为EosinY。
优选的,所述步骤中的添加剂为甲酸、乙二酸、苯甲酸、一水柠檬酸,最优选为一水柠檬酸。
优选的,所述步骤中的有机溶剂为乙醇、乙腈,最优选为乙醇。
优选的,所述步骤中的温度为26℃至50℃,最优选为室温26℃。
优选的,所述可见光光源为18W LED白光或者蓝光,最优选为LED蓝光,可见光照射反应液的时间为12-18小时。
在本发明所述的制备方法中,式(II)所示的化合物和式(III)所示的化合物的摩尔比优选为1:1~1:1.5,最优选为1:1.2。
本发明的方法是在室温空气氛围中,曙红Y作光敏剂,一水柠檬酸为添加剂,乙醇作为反应溶剂,一步合成3-亚胺基咪唑并[1,2-a]吡啶化合物。反应操作简单、条件温和、原子经济、化学选择性好并且对环境友好,具有非常好的应用前景。
具体实施方式
以下通过具体实施例对本发明作进一步详细说明,但本发明的实施方式不限于此。
实施例1
将N-4-甲苯基甘氨酸乙酯(0.15mmol),2-苯基咪唑并[1,2-a]吡啶(0.18mmol),曙红Y(0.015mmol)和一水柠檬酸(0.18mmol)加入到带有搅拌磁子的干燥反应试管中。然后向试管中加入乙醇(2mL)作溶剂并将反应混合液置于空气氛围中室温下18W LED蓝光照射反应18小时。待TLC检测反应结束后,溶剂用旋转蒸发仪减压蒸馏除去,残留物经柱层析分离纯化得到纯净的黄色固体3aa,产率为73%。3aa化合物的结构表征数据如下:
Light yellow solid;mp 164.4-168.8℃;1H NMR(500MHz,CDCl3):δ9.79(d,J=7.0Hz,1H),7.79(d,J=8.9Hz,1H),7.61(dd,J=6.6Hz,J=3.0Hz,2H),7.50-7.46(m,1H),7.40(dd,J=5.0Hz,J=1.7Hz,3H),7.12(d,J=8.0Hz,2H),7.03(td,J=6.9Hz,J=1.2Hz,1H),6.84(d,J=8.2Hz,2H),3.36(q,J=7.2Hz,2H),2.33(s,3H),0.76(t,J=7.2Hz,3H);13CNMR(100MHz,CDCl3):δ162.3,153.1,151.8,147.3,147.1,134.2,134.0,129.9,129.3,128.8,128.6,128.1,127.9,119.7,117.3,116.7,114.0,61.2,20.8,13.1;HRMS(ESI)calcdfor C24H22N3O2(M+H)+384.1707,found 384.17027.
实施例2
将N-3-甲苯基甘氨酸乙酯(0.15mmol),2-苯基咪唑并[1,2-a]吡啶(0.18mmol),曙红Y(0.015mmol)和一水柠檬酸(0.18mmol)加入到带有搅拌磁子的干燥反应试管中。然后向试管中加入乙醇(2mL)作溶剂并将反应混合液置于空气氛围中室温下18W LED蓝光照射反应18小时。待TLC检测反应结束后,溶剂用旋转蒸发仪减压蒸馏除去,残留物经柱层析分离纯化得到纯净的淡黄色固体3ab,产率为53%。3ab化合物的结构表征数据如下:
Light yellow solid;mp 161.4-164.3℃;1H NMR(500MHz,CDCl3):δ9.81(d,J=7.0Hz,1H),7.80(d,J=9.0Hz,1H),7.63(dd,J=7.5Hz,J=4.0Hz,2H),7.51-7.47(m,1H),7.43-7.40(m,3H),7.22(t,J=7.5Hz,1H),7.04(t,J=7.0Hz,1H),6.96(d,J=7.5Hz,1H),6.80(s,1H),6.75(d,J=8.0Hz,1H),3.38(q,J=7.5Hz,2H),2.35(s,3H),0.77(t,J=7.5Hz,3H);13C NMR(100MHz,CDCl3):δ162.3,153.3,151.8,149.7,147.1,138.6,133.7,129.9,128.9,128.7,128.6,128.4,128.0,125.4,120.6,117.3,116.7,116.6,114.1,61.2,21.4,13.2;HRMS(ESI)calcd for C24H22N3O2(M+H)+384.1701,found 384.17106.
实施例3
将N-苯基甘氨酸乙酯(0.15mmol),2-苯基咪唑并[1,2-a]吡啶(0.18mmol),曙红Y(0.015mmol)和一水柠檬酸(0.18mmol)加入到带有搅拌磁子的干燥反应试管中。然后向试管中加入乙醇(2mL)作溶剂并将反应混合液置于空气氛围中室温下18W LED蓝光照射反应17小时。待TLC检测反应结束后,溶剂用旋转蒸发仪减压蒸馏除去,残留物经柱层析分离纯化得到纯净的淡黄色固体3ac,产率为73%。3ac化合物的结构表征数据如下:
Light yellow solid;mp 162.9-164.6℃;1H NMR(500MHz,CDCl3):δ9.80(d,J=7.0Hz,1H),7.80(d,J=9.0Hz,1H),7.63-7.60(m,2H),7.51-7.47(m,1H),7.42-7.39(m,3H),7.34-7.30(m,2H),7.13(t,J=7.5Hz,1H),7.04(td,J=7.0Hz,J=1.0Hz,1H),6.93(dd,J=8.5Hz,J=1.0Hz,2H),3.35(q,J=7.0Hz,2H),0.73(t,J=7.0Hz,3H);13C NMR(100MHz,CDCl3):δ162.2,153.4,152.1,149.8,147.2,133.8,129.9,129.0,128.8,128.7,128.4,128.0,124.6,119.7,117.3,116.5,114.2,61.3,13.2;HRMS(ESI)calcd forC23H20N3O2(M+H)+370.155,found 370.15541.
实施例4
将N-4-苯基苯基甘氨酸乙酯(0.15mmol),2-苯基咪唑并[1,2-a]吡啶(0.18mmol),曙红Y(0.015mmol)和一水柠檬酸(0.18mmol)加入到带有搅拌磁子的干燥反应试管中。然后向试管中加入乙醇(2mL)作溶剂并将反应混合液置于空气氛围中室温下18W LED蓝光照射反应16小时。待TLC检测反应结束后,溶剂用旋转蒸发仪减压蒸馏除去,残留物经柱层析分离纯化得到纯净的淡黄色固体3ad,产率为68%。3ad化合物的结构表征数据如下:
Light yellow solid;mp 141.8-142.9℃;1H NMR(500MHz,CDCl3):δ9.81(d,J=7.0Hz,1H),7.80(d,J=9.0Hz,1H),7.61(m,6H),7.51-7.47(m,1H),7.46-7.40(m,5H),7.33(t,J=7.5Hz,1H),7.07-7.00(m,3H),3.39(q,J=7.5Hz,2H),0.76(t,J=7.0Hz,3H);13CNMR(100MHz,CDCl3):δ162.2,153.6,152.1,149.1,147.2,140.6,137.6,133.9,129.9,129.0,128.8,128.6,128.4,128.0,127.5,127.1,126.8,120.3,117.4,116.6,114.2,61.4,13.2;HRMS(ESI)calcd forC29H24N3O2(M+H)+446.1863,found446.18807.
实施例5
将N-4-甲苯基甘氨酸甲酯(0.15mmol),2-(4-氯基苯基)咪唑并[1,2-a]吡啶(0.18mmol),曙红Y(0.015mmol)和一水柠檬酸(0.18mmol)加入到带有搅拌磁子的干燥反应试管中。然后向试管中加入乙醇(2mL)作溶剂并将反应混合液置于空气氛围中室温下18WLED蓝光照射反应时。待TLC检测反应结束后,溶剂用旋转蒸发仪减压蒸馏除去,残留物经柱层析分离纯化得到纯净的淡黄色固体3af,产率为79%。3af化合物的结构表征数据如下:
Light yellow solid;mp 171.3-173.2℃;1H NMR(500MHz,CDCl3):δ9.79(d,J=7.0Hz,1H),7.78(d,J=8.9Hz,1H),7.60(dd,J=7.5Hz,J=2.0Hz,2H),7.49-7.45(m,1H),7.43-7.39(m,3H),7.13(d,J=8.0Hz,2H),7.02(td,J=6.9Hz,J=1.2Hz,1H),6.84(d,J=8.2Hz,2H),2.96(s,3H),2.33(s,3H);13C NMR(100MHz,CDCl3):δ162.8,153.3,151.2,147.2,147.1,134.5,133.9,129.8,129.5,128.8,128.6,128.3,128.0,119.7,117.3,116.7,114.1,51.7,21.0;HRMS(ESI)calcd for C23H20N3O2(M+H)+370.155,found370.15624.
实施例6
将N-4-甲苯基甘氨酸苯甲酯(0.15mmol),2-(4-氯基苯基)咪唑并[1,2-a]吡啶(0.18mmol),曙红Y(0.015mmol)和一水柠檬酸(0.18mmol)加入到带有搅拌磁子的干燥反应试管中。然后向试管中加入乙醇(2mL)作溶剂并将反应混合液置于空气氛围中室温下18WLED蓝光照射反应18小时。待TLC检测反应结束后,溶剂用旋转蒸发仪减压蒸馏除去,残留物经柱层析分离纯化得到纯净的淡黄色固体3ae,产率为67%。3ae化合物的结构表征数据如下:
Light yellow solid;mp 161.4-162.4℃;1H NMR(500MHz,CDCl3):δ9.76(d,J=7.0Hz,1H),7.77(d,J=9.0Hz,1H),7.64(dd,J=7.0Hz,J=1.5Hz,2H),7.48-7.40(m,4H),7.25(dq,J=16.0Hz,J=7.0Hz,3H),7.05(d,J=8.0Hz,2H),7.00(td,J=7.0Hz,J=1.0Hz,1H),6.81(dd,J=11.5Hz,J=7.5Hz,4H),4.26(s,2H),2.32(s,3H);13C NMR(100MHz,CDCl3):δ162.3,153.3,151.3,147.2,147.1,134.4,134.1,134.0,130.0,129.5,129.0,128.7,128.6,128.4,128.3,128.1,119.8,117.3,116.7,114.1,67.3,21.0;HRMS(ESI)calcd for C29H24N3O2(M+H)+446.1863,found 446.18673.
实施例7
将N-4-甲苯基甘氨酸乙酯(0.15mmol),2-(4-甲基苯基)咪唑并[1,2-a]吡啶(0.18mmol),曙红Y(0.015mmol)和一水柠檬酸(0.18mmol)加入到带有搅拌磁子的干燥反应试管中。然后向试管中加入乙醇(2mL),并将反应混合液置于空气氛围中室温下18W LED蓝光照射反应18小时。待TLC检测反应结束后,溶剂用旋转蒸发仪减压蒸馏除去,残留物经柱层析分离纯化得到纯净的淡黄色固体3ba,产率为89%。3ba化合物的结构表征数据如下:
Light yellow solid;mp 139.1-141.4℃;1H NMR(400MHz,CDCl3):δ9.77(d,J=6.8Hz,1H),7.76(d,J=8.8Hz,1H),7.55-7.40(m,3H),7.20(d,J=8.0Hz,2H),7.12(d,J=8.0Hz,2H),7.00(t,J=6.8Hz,1H),6.83(d,J=84Hz,2H),3.40(q,J=7.2Hz,2H),2.37(s,3H),2.32(s,3H),0.77(t,J=7.2Hz,3H);13C NMR(100MHz,CDCl3):δ162.4,153.4,151.9,147.3,147.2,138.7,134.2,131.1,131.0,129.8,129.3,128.6,128.1,119.7,117.3,116.6,113.7,61.2,21.3,20.9,13.1;HRMS(ESI)calcd for C25H22N3O2(M-H)-396.1707,found 397.17908.
实施例8
N-4-甲苯基甘氨酸乙酯(0.15mmol),2-(4-甲氧基苯基)咪唑并[1,2-a]吡啶(0.18mmol),曙红Y(0.015mmol)和一水柠檬酸(0.18mmol)加入到带有搅拌磁子的干燥反应试管中。然后向试管中加入乙醇(2mL)作溶剂并将反应混合液置于空气氛围中室温下18WLED蓝光照射反应18小时。待TLC检测反应结束后,溶剂用旋转蒸发仪减压蒸馏除去,残留物经柱层析分离纯化得到纯净的淡黄色固体3ca,产率为53%。3ca化合物的结构表征数据如下:
Light yellow solid;mp 141.8-143.6℃;1H NMR(500MHz,CDCl3):δ9.76(d,J=7.0Hz,1H),7.76(d,J=9.0Hz,1H),7.55(d,J=9.0Hz,2H),7.47-7.43(m,1H),7.12(d,J=8.0Hz,2H),7.00(td,J=7.0Hz,J=1.0Hz,1H),6.93(d,J=8.5Hz,2H),6.84(d,J=8.0Hz,2H),3.83(s,3H),3.45(q,J=7.0Hz,2H),2.33(s,3H),0.79(t,J=7.0Hz,3H);13C NMR(100MHz,CDCl3):δ162.5,160.3,153.0,151.8,147.4,147.0,134.2,131.2,129.4,128.5,128.2,126.4,119.8,117.2,116.5,114.0,113.5,61.4,55.3,20.8,13.2;HRMS(ESI)calcdfor C25H24N3O3(M+H)+414.1812,found 414.18104.
实施例9
将N-4-甲苯基甘氨酸乙酯(0.15mmol),2-(4-氟基苯基)咪唑并[1,2-a]吡啶(0.18mmol),曙红Y(0.015mmol)和一水柠檬酸(0.18mmol)加入到带有搅拌磁子的干燥反应试管中。然后向试管中加入乙醇(2mL)作溶剂并将反应混合液置于空气氛围中室温下18WLED蓝光照射反应17小时。待TLC检测反应结束后,溶剂用旋转蒸发仪减压蒸馏除去,残留物经柱层析分离纯化得到纯净的黄色固体3da,产率为60%。3da化合物的结构表征数据如下:
Light yellow solid;mp 151.9-155.4℃;1H NMR(500MHz,CDCl3):δ9.77(d,J=5.0Hz,1H),7.77(d,J=9.0Hz,1H),7.62-7.57(m,2H),7.50-7.45(m,1H),7.14-7.08(m,4H),7.03(td,J=7.0Hz,J=1.0Hz,1H),6.83(d,J=8.5Hz,2H),3.45(q,J=7.5Hz,2H),2.33(s,3H),0.79(t,J=7.0Hz,3H);13C NMR(125MHz,CDCl3):δ164.3,162.2(d,J=258.8Hz),152.0,151.6,147.2,147.0,134.4,131.8(d,J=8.25Hz),130.1(d,J=3.0Hz),129.4,128.7,128.4,119.7,117.3,116.7,115.1(d,J=21.5Hz),114.1,61.4,21.1,13.2;HRMS(ESI)calcd for C24H21FN3O2(M+H)+402.1612,found402.16084.
实施例10
将N-4-甲苯基甘氨酸乙酯(0.15mmol),6-甲基2-苯基咪唑并[1,2-a]吡啶(0.18mmol),曙红Y(0.015mmol)和一水柠檬酸(0.18mmol)加入到带有搅拌磁子的干燥反应试管中。然后向试管中加入乙醇(2mL)作溶剂并将反应混合液置于空气氛围中室温下18WLED蓝光照射反应18小时。待TLC检测反应结束后,溶剂用旋转蒸发仪减压蒸馏除去,残留物经柱层析分离纯化得到纯净的淡黄色固体3ea,产率为80%。3ea化合物的结构表征数据如下:
Light yellow solid;mp 152.4-155.3℃;1H NMR(400MHz,CDCl3):δ9.57(s,1H),7.67(d,J=9.2Hz,1H),7.61-7.56(m,2H),7.41-7.36(m,3H),7.32(d,J=8.8Hz,1H),7.13(d,J=8.0Hz,2H),6.85(d,J=8.0Hz,2H),3.34(q,J=7.2Hz,2H),2.39(s,3H),2.33(s,3H),0.75(t,J=6.8Hz,3H);13C NMR(100MHz,CDCl3):δ162.4,153.1,152.0,147.4,146.0,134.2,131.1,130.1,129.3,128.7,127.9,126.4,124.0,120.3,119.8,116.6,116.4,61.2,21.0,18.5,12.9;HRMS(ESI)calcd for C25H22N3O2(M-H)-396.1707,found 397.17926
实施例11
将N-4-甲苯基甘氨酸乙酯(0.15mmol),5-甲基2-苯基咪唑并[1,2-a]吡啶(0.18mmol),曙红Y(0.015mmol)和一水柠檬酸(0.18mmol)加入到带有搅拌磁子的干燥反应试管中。然后向试管中加入乙醇(2mL)作溶剂并将反应混合液置于空气氛围中室温下18WLED蓝光照射反应18小时。待TLC检测反应结束后,溶剂用旋转蒸发仪减压蒸馏除去,残留物经柱层析分离纯化得到纯净的淡黄色固体3fa,产率为82%。3fa化合物的结构表征数据如下:
Light yellow solid;mp 166.7-170.1℃;1H NMR(500MHz,CDCl3):δ9.66(d,J=7.0Hz,1H),7.59(dd,J=7.5Hz,J=4.0Hz,2H),7.54(d,J=0.5Hz,1H),7.41-7.37(m,3H),7.11(d,J=8.5Hz,2H),6.84(dd,J=9.0Hz,J=1.5Hz,3H),3.35(q,J=7.0Hz,2H),2.49(s,3H),2.33(s,3H),0.76(t,J=7.0Hz,3H);13C NMR(100MHz,CDCl3):δ162.5,153.3,151.8,147.5,147.4,139.8,134.2,134.1,129.9,129.4,128.9,128.0,127.9,119.8,116.6,116.3,115.9,61.2,21.5,21.0,13.3;HRMS(ESI)calcd for C25H24N3O2(M+H)+398.1863,found 398.18602.
实施例12
将N-4-甲苯基甘氨酸乙酯(0.15mmol),4-甲基2-苯基咪唑并[1,2-a]吡啶(0.18mmol),曙红Y(0.015mmol)和一水柠檬酸(0.18mmol)加入到带有搅拌磁子的干燥反应试管中。然后向试管中加入乙醇(2mL)作溶剂并将反应混合液置于空气氛围中室温下18WLED蓝光照射反应18小时。待TLC检测反应结束后,溶剂用旋转蒸发仪减压蒸馏除去,残留物经柱层析分离纯化得到纯净的黄色固体3ga,产率为82%。3ga化合物的结构表征数据如下:
Light yellow solid;mp 128.9-132.7℃;1H NMR(500MHz,CDCl3):δ9.65(d,J=7.0Hz,1H),7.62-7.59(m,2H),7.41-7.37(m,3H),7.28-7.24(m,1H),7.11(d,J=8.0Hz,2H),6.93(t,J=7.0Hz,1H),6.83(d,J=8.5Hz,2H),3.33(q,J=7.5Hz,2H),2.71(s,3H),2.32(s,3H),0.76(t,J=7.0Hz,3H);13C NMR(100MHz,CDCl3):δ162.5,152.7,151.9,147.4,147.2,134.2,134.1,130.2,129.4,128.8,128.0,127.3,127.2,126.4,119.8,117.1,114.1,60.8,20.6,16.9,13.0;HRMS(ESI)calcd for C25H24N3O2(M+H)+398.1863,found398.18592.
实施例13
将N-4-甲苯基甘氨酸乙酯(0.15mmol),4-甲基-2-(4-甲基苯基)咪唑并[1,2-a]吡啶(0.18mmol),曙红Y(0.015mmol)和一水柠檬酸(0.18mmol)加入到带有搅拌磁子的干燥反应试管中。然后向试管中加入乙醇(2mL)作溶剂并将反应混合液置于空气氛围中室温下18WLED蓝光照射反应18小时。待TLC检测反应结束后,溶剂用旋转蒸发仪减压蒸馏除去,残留物经柱层析分离纯化得到纯净的黄色固体3ha,产率为94%。3ha化合物的结构表征数据如下:
Light yellow solid;mp 144.3-145.2℃;1H NMR(500MHz,CDCl3):δ9.63(d,J=6.9Hz,1H),7.50(d,J=8.0Hz,2H),7.21(dd,J=16.9Hz,J=7.4Hz,3H),7.11(d,J=8.0Hz,2H),6.90(t,J=6.9Hz,1H),6.83(d,J=8.2Hz,2H),3.36(q,J=7.2Hz,2H),2.70(s,3H),2.36(s,3H),2.32(s,3H),0.76(t,J=7.2Hz,3H);13C NMR(100MHz,CDCl3):δ162.6,152.9,152.0,147.4,147.3,138.6,134.0,131.3,130.3,129.4,128.6,127.2,127.0,126.3,119.8,117.0,113.9,61.1,21.4,20.9,17.2,13.3;HRMS(ESI)calcd for C26H26N3O2(M+H)+412.202,found 412.2017.
实施例14
N-4-甲苯基甘氨酸乙酯(0.15mmol),2-(3,4-二甲氧基苯基)咪唑并[1,2-a]吡啶(0.18mmol),曙红Y(0.015mmol)和一水柠檬酸(0.18mmol)加入到带有搅拌磁子的干燥反应试管中。然后向试管中加入乙醇(2mL)作溶剂并将反应混合液置于空气氛围中室温下18WLED蓝光照射反应18小时。待TLC检测反应结束后,溶剂用旋转蒸发仪减压蒸馏除去,残留物经柱层析分离纯化得到纯净的淡黄色固体3ia,产率为41%。3ia化合物的结构表征数据如下:
Light yellow solid;mp 134.4-136.1℃;1H NMR(500MHz,CDCl3):δ9.79(d,J=7.0Hz,1H),7.78(d,J=8.9Hz,1H),7.49-7.45(m,1H),7.19-7.11(m,4H),7.01(td,J=6.9Hz,J=0.8Hz,1H),6.89(d,J=8.1Hz,1H),6.84(d,J=8.2Hz,2H),3.92(d,J=10.6Hz,6H),3.47(d,J=21.5Hz,2H),2.34(s,3H),0.79(t,J=7.2Hz,3H);13C NMR(100MHz,CDCl3):δ162.5,153.1,151.8,149.6,148.5,147.3,147.0,134.3,129.3,128.6,128.3,126.6,122.9,119.6,117.2,116.5,113.9,112.5,110.5,61.3,55.9,55.8,20.9,13.2;HRMS(ESI)calcd for C26H26N3O4(M+H)+444.1918,found 444.19193.
实施例15
将N-4-甲苯基甘氨酸乙酯(0.15mmol),2-(4-氯基苯基)咪唑并[1,2-a]吡啶(0.18mmol),曙红Y(0.015mmol)和一水柠檬酸(0.18mmol)加入到带有搅拌磁子的干燥反应试管中。然后向试管中加入乙醇(2mL)作溶剂并将反应混合液置于空气氛围中室温下18WLED蓝光照射反应19小时。待TLC检测反应结束后,溶剂用旋转蒸发仪减压蒸馏除去,残留物经柱层析分离纯化得到纯净的淡黄色固体3ja,产率为33%。3ja化合物的结构表征数据如下:
Light yellow solid;mp 142.6-145.8℃;1H NMR(400MHz,CDCl3):δ9.76(d,J=6.8Hz,1H),7.78(d,J=8.8Hz,1H),7.60-7.44(m,3H),7.38(d,J=8.4Hz,2H),7.13(d,J=8.0Hz,2H),7.04(t,J=7.2Hz,1H),6.83(d,J=8.0Hz,2H),3.45(q,J=7.2Hz,2H),2.34(s,3H),0.79(t,J=7.2Hz,3H);13C NMR(100MHz,CDCl3):δ162.5,151.7,151.5,147.2,147.1,135.1,134.5,132.6,131.2,129.4,128.6,128.4,128.2,119.7,117.4,116.7,114.2,61.2,20.6,13.2;HRMS(ESI)calcd for C24H21ClN3O2(M+H)+418.1317,found418.13135.
实施例16
将N-4-甲苯基甘氨酸乙酯(0.15mmol),2-甲基咪唑并[1,2-a]吡啶(0.18mmol),曙红Y(0.015mmol)和一水柠檬酸(0.18mmol)加入到带有搅拌磁子的干燥反应试管中。然后向试管中加入乙醇(2mL)作溶剂并将反应混合液置于空气氛围中室温下18W LED蓝光照射反应19小时。待TLC检测反应结束后,溶剂用旋转蒸发仪减压蒸馏除去,残留物经柱层析分离纯化得到纯净的淡黄色固体3ka,产率为50%。3ka化合物的结构表征数据如下:
Light yellow solid;mp 128.4-131.1℃;1H NMR(400MHz,CDCl3):δ9.81(d,J=7.2Hz,1H),7.65(d,J=8.8Hz,1H),7.40(t,J=8.0Hz 1H),7.14(d,J=8.0Hz,2H),6.97(t,J=6.8Hz,1H),6.88(d,J=8.0Hz,2H),4.15(q,J=7.2Hz,2H),2.52(s,3H),2.35(s,3H),1.08(t,J=7.2Hz,3H);13C NMR(100MHz,CDCl3):δ163.7,151.7,150.4,147.2,147.0,134.1,129.3,129.1,127.8,120.1,116.4,116.2,113.7,61.7,20.9,15.4,13.6;HRMS(ESI)calcd for C19H20N3O2(M+H)+322.155,found 322.15483.
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 (8)
1.一种3-亚胺基咪唑并[1,2-a]吡啶化合物,其特征在于,结构式(I)如下:
其中,R1为氢、供电子基团或吸电子基团,当其为供电子基团时,所述供电子基团为甲基;当其为吸电子基团时,所述吸电子基团为苯基;
R2为烷基或苄基,当R2为烷基时,具体为甲基、乙基、异丙基或叔丁基中的一种;
R3与吡啶环相连接,具体是氢、供电子基团或吸电子基团;当R3为供电子基团时,所述的供电子基团为甲基;
R4为烷基、芳基或取代的芳基;
当R4为烷基时,具体为甲基;
当R4为芳基时,所述的芳基为苯基;
当R4为取代的芳基时,所述取代的芳基为3,4-二甲氧基苯基、4-甲氧基苯基、4-甲苯基、4-氟苯基、4-氯苯基、4-溴苯基中的一种。
2.一种3-亚胺基咪唑并[1,2-a]吡啶化合物的制备方法,具体合成步骤如下:可见光照射下,以曙红Y为光催化剂,一水柠檬酸为添加剂,N-芳基甘氨酸酯(II)和咪唑并[1,2-a]吡啶化合物(III)在有机溶剂中,空气氛围下26℃至50℃搅拌反应12-18小时,至TLC检测反应完全,反应液浓缩后用乙酸乙酯/石油醚硅胶柱层析分离,可制得产物3-亚胺基咪唑并[1,2-a]吡啶化合物,反应通式如下:
3.根据权利要求2所述的一种3-亚胺基咪唑并[1,2-a]吡啶化合物的制备方法,其特征在于,所述步骤中的光敏剂还可以是Ru(bpy3)Cl2·6H2O、Eosin B、Ir(bpy)3或Acr+-Mes-ClO4 -中的一种。
4.根据权利要求2所述的一种3-亚胺基咪唑并[1,2-a]吡啶化合物的制备方法,其特征在于,所述步骤中的添加剂还可以是为甲酸、乙二酸或苯甲酸中的一种。
5.根据权利要求2所述的一种3-亚胺基咪唑并[1,2-a]吡啶化合物的制备方法,其特征在于,所述步骤中的有机溶剂为乙醇或乙腈。
6.根据权利要求2所述的一种3-亚胺基咪唑并[1,2-a]吡啶化合物的制备方法,其特征在于,所述步骤中的温度为26℃至50℃。
7.根据权利要求2所述的一种3-亚胺基咪唑并[1,2-a]吡啶化合物的制备方法,其特征在于,所述可见光光源为LED白光或者蓝光,采用可见光照射反应液的时间为12~18小时。
8.根据权利要求2所述的一种3-亚胺基咪唑并[1,2-a]吡啶化合物的制备方法,其特征在于,式(II)所示的化合物和式(III)所示的化合物的摩尔比为1:1~1:1.5。
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