CN112778186B - 吡咯类化合物的合成方法 - Google Patents

吡咯类化合物的合成方法 Download PDF

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CN112778186B
CN112778186B CN202110129957.6A CN202110129957A CN112778186B CN 112778186 B CN112778186 B CN 112778186B CN 202110129957 A CN202110129957 A CN 202110129957A CN 112778186 B CN112778186 B CN 112778186B
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魏晔
林靖
蒋坤
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Abstract

本发明公开了一种吡咯类化合物的合成方法，该方法有以下步骤：取肟酯类化合物1、苯并呋喃亚胺类化合物2、一价铜化合物，惰性保护气体下加入有机溶剂，60‑120℃条件下反应，TLC监测反应进程，反应完毕后，降至室温，饱和食盐水和乙酸乙酯萃取，合并有机相，旋转蒸发去除溶剂得粗品，快速柱层析，得吡咯类化合物3。该方法合成方法路线简短，利用C‑C和C‑N键形成，一步构建吡咯类化合物，原子经济性高、效能优越，反应产率高达95％，实现了该体系化学合成的突破性进展。

Description

吡咯类化合物的合成方法
技术领域
本发明属于有机化合物合成领域，特别涉及一种吡咯类化合物的合成方法。
背景技术
吡咯结构是最普遍的五元杂环之一，并存在于大量天然产物、药物和功能性材料中。吡咯具有显著的生物学和药理特性，例如抗菌、抗真菌、抗炎、抗氧化、抗肿瘤和离子性。它还可以作为逆转录病毒逆转录酶[即人类免疫缺陷病毒1型(HIV-1)]，聚(ADP-核糖)聚合酶，脯氨酰-4-羟化酶，细胞DNA聚合酶，糖原合酶激酶3(GSK-3)和蛋白激酶抑制剂。在功能材料研究中，因为它们具有光电材料的潜力所以吡咯及其衍生物一直是材料科学家关注的焦点，例如聚合物发光二极管(PLED)、有机发光二极管(OLED)、薄膜晶体管、非线性光学聚合物、衍生自六(N-吡咯基)苯的高性能半导体，以及基于聚吡咯-乳胶材料和聚吡咯材料的用于检测和鉴别挥发性有机化合物的葡萄糖传感器。因此，已经开发出许多合成策略来获得这一重要类别的化合物。传统方法包括Knorr、Hantzsch和Paal–Knorr反应，通过羰基化合物和胺的缩合反应构建多取代的吡咯。然而这些方法，通常需要在较高的反应温度下使用强酸促进缩合，这也导致了底物范围和官能团受限。近年来也开发了一些可以在相对温和的条件下合成具有更好的区域选择性的吡咯的方法，例如：多组分反应和过渡金属催化的偶联。但是这些方法通常需要高度官能化的起始原料(例如亚氨基丙二烯，炔基氮丙啶或叠氮化物)，因此限制了产物的范围。此外，许多现有策略需要使用具有受保护氮的底物，因此在合成吡咯环后需要将保护基团除去或更换，这大大降低了该工艺的效率。
因此，发展一种简洁、高效、实用性的催化合成吡咯类化合物的方法可以为药物研发、小分子药物的高通量筛选以及功能材料的合成提供切实可靠的新方法，具有十分重要的研究意义和应用前景。
发明内容
本发明的目的是提供一种吡咯类化合物的合成方法，该方法合成方法路线简短，利用C-C和C-N键形成，一步构建吡咯类化合物，原子经济性高、效能优越，反应产率高达95％，实现了该体系化学合成的突破性进展。
本发明所述方法是氩气保护下，以肟酯类化合物和苯并呋喃亚胺类化合物为原料，在Cu化合物催化作用下反应得到吡咯类化合物，具体方案为：
一种吡咯类化合物的合成方法，有以下步骤：
取肟酯类化合物1、苯并呋喃亚胺类化合物2、一价铜化合物，惰性保护气体下加入有机溶剂，60-120℃条件下反应，TLC监测反应进程，反应完毕后，降至室温，乙酸乙酯萃取后用饱和食盐水洗涤，合并有机相，旋转去除溶剂得粗品，快速柱层析，得吡咯类化合物3；
其反应式为：
Figure BDA0002924773480000021
所述肟酯类化合物1中R1为芳基、烷基或酯基；R2为苯基或烷基。
所述苯并呋喃类化合物2中R3为H或甲氧基；R4为芳基；R5为氰基、卤素、烷基或烷氧基。
所述吡咯类化合物3中R1为芳基、烷基或酯基；R2为苯基或烷基；R3为H或甲氧基；R4为芳基；R5为氰基、卤素、烷基或烷氧基。
所述肟酯类化合物1:苯并呋喃亚胺类化合物2的mmol比为0.1～5:0.12～6。
所述反应时间为16小时。
所述萃取中的乙酸乙酯萃取3次。
所述催化剂为CuCl、CuBr、CuI、CuOAc、CuCl2、CuBr2、CuI2或Cu(OAc)2。
所述有机溶剂为DMSO、THF、1,4-dioxane、Toluene、DMF、DCE、DCM。
所述惰性保护气体为氩气。
本发明利用过渡金属催化断裂肟酯类化合物N-O键生成自由基来实现C-C、C-N键的快速构建，因其合成策略具有环境友好、高效、高选择性和原子经济性的优点，实现了Cu金属催化N-O键断裂，完成了肟酯类化合物和苯并呋喃亚胺类化合物反应一步构建吡咯类化合物。该反应原料廉价易得、步骤简短、方法原子经济性高。
本发明的有益效果是，所使用的各原料简单易得，均为工业化商品，来源广泛，价格低廉，并且性质稳定，保存条件不苛刻；其次，本发明合成路线简短，利用C-C和C-N键形成，一步构建吡咯类化合物，原子经济性高、效能优越，反应产率高达95％，实现了该体系化学合成的突破性进展，并促进该体系相关药物化学研究的深层次扩展。
具体实施方式
以下实施例所给出的数据包括具体操作和反应条件及产物，产物纯度均通过核磁鉴定。
本发明所述试剂均采用市售的分析纯试剂。
实施例1
Figure BDA0002924773480000041
将取10mL的反应管，将称量好的肟酯类化合物1a(0.2mmol)、苯并呋喃亚胺类化合物2a(0.24mmol)、CuCl(0.02mmol)加入其中，然后在惰性气体保护下，加入DMSO(2mL)后，将反应管用聚四氟乙烯的塞子密封。将反应管置于80℃的油浴锅中搅拌16小时，反应完毕后，降至室温，用(20mL×3)乙酸乙酯萃取三次，40mL饱和食盐水洗涤，合并有机相，旋转蒸发去除溶剂得到含有3aa的混合物，然后快速柱层析得产物3aa，收率95％。
1H NMR(600MHz,CDCl3)δ11.01(s,1H),10.78(s,1H),7.82(d,J＝7.8Hz,2H),7.64(d,J＝7.8Hz,2H),7.30(d,J＝7.8Hz,2H),7.25(m,2H),7.04(d,J＝7.8Hz,1H),7.00-7.07(m,4H),6.93(d,J＝6.6Hz,2H),6.72-6.75(m,2H),2.42(s,3H),2.36(s,3H).13C NMR(151MHz,CDCl3)δ168.3,160.5,144.0,139.1,139.0,138.4,137.5,135.0,134.5,130.0,129.6,128.8,127.9,127.5,127.0,126.7,125.0,122.3,119.5,118.9,117.4,109.7,21.5,21.3.；(ESI)计算值C31H26N2O3S,[M+H]+507.1734，实际值507.1737。
实施例2
(1)
Figure BDA0002924773480000051
将取10mL的反应管，将称量好的肟酯类化合物1b(0.12mmol)、苯并呋喃亚胺类化合物2a(0.1mmol)、CuBr(0.01mmol)加入其中，然后在惰性气体保护下，加入DMSO(1mL)后，将反应管用聚四氟乙烯的塞子密封。将反应管置于80℃的油浴锅中搅拌10小时，反应完毕后，降至室温，用(20mL×3)乙酸乙酯萃取三次，40mL饱和食盐水洗涤，合并有机相，旋转蒸发去除溶剂得到含有3ba的混合物，然后快速柱层析得产物3ba，收率52％。
1H NMR(600MHz,CDCl3)δ11.08(s,1H),10.79(s,1H),7.84(d,J＝7.2Hz,2H),7.76(d,J＝7.0Hz,2H),7.50(t,J＝6.8Hz,2H),7.40(t,J＝7.0Hz,1H),7.27(s,1H),7.11(d,J＝6.7Hz,1H),7.08–6.99(m,4H),6.95(d,J＝6.5Hz,2H),6.81–6.72(m,2H),6.27(t,J＝7.0Hz,1H),2.37(s,3H).13C NMR(151MHz,CDCl3)δ168.6,160.7,144.1,138.7,138.0,137.4,135.1,134.5,134.4,130.3,129.6,129.3,128.7,128.0,127.0,126.8,125.1,122.4,119.3,119.0,117.5,109.9,21.5.HRMS(ESI)计算值C30H24N2O3S[M+H]+493.1579，实际值493.1580。
(2)
Figure BDA0002924773480000052
操作步骤同实施例1，得到产物3ba，产率为90％。
实施例3
Figure BDA0002924773480000061
操作步骤同实施例1，得到产物3da，产率为82％。
1H NMR(600MHz,CDCl3)δ11.03(s,1H),10.79(s,1H),7.82(d,J＝8.1Hz,2H),7.69(d,J＝8.3Hz,2H),7.52(d,J＝8.3Hz,2H),7.27–7.23(m,2H),7.11–6.98(m,5H),6.93(d,J＝6.8Hz,2H),6.71–6.76(m,2H),6.25(t,J＝7.6Hz,1H),2.36(s,3H),1.37(s,9H).13C NMR(151MHz,CDCl3)δ168.4,160.6,152.2,144.0,139.1,138.4,137.5,135.0,134.5,129.6,128.8,127.9,127.4,127.0,126.7,126.3,124.9,122.3,119.5,118.9,117.4,109.8,34.8,31.2,21.5；(ESI)计算值C34H32N2O3S,[M+H]+549.2205，实际值549.2206。
实施例4
Figure BDA0002924773480000062
操作步骤同实施例1，得到产物3ea，产率为65％。
1H NMR(600MHz,CDCl3)δ10.92(s,1H),10.79(s,1H),7.83(d,J＝7.6Hz,2H),7.71(d,J＝8.2Hz,2H),7.27(s,1H),7.11–7.00(m,7H),6.95(d,J＝6.7Hz,2H),6.75(d,J＝8.1Hz,1H),6.68(s,1H),6.25(t,J＝7.2Hz,1H),3.88(s,3H),2.37(s,3H).13C NMR(151MHz,CDCl3)δ167.9,160.3,143.9,143.5,139.3,138.9,137.6,134.8,134.5,134.5,129.6,129.6,128.8,127.9,127.0,126.7,126.6,126.4,123.0,122.3,119.6,118.9,117.4,114.8,109.6,55.4,21.5.(ESI)计算值C31H26N2O4S,[M+H]+523.1684，实际值523.1686。
实施例5
Figure BDA0002924773480000071
操作步骤同实施例1，得到产物3fa，产率为43％。
1H NMR(600MHz,DMSO)δ11.76(s,1H),9.44(s,1H),7.93(d,J＝6.9Hz,2H),7.41–7.59(m,4H),7.22(d,J＝7.9Hz,2H),6.85–7.04(m,7H),6.73(s,1H),6.49(s,1H),6.33(s,1H),2.33(s,3H).(ESI)计算值C30H23ClN2O3S,[M+H]+527.1189，实际值527.1191。
实施例6
Figure BDA0002924773480000072
操作步骤同实施例1，得到产物3ga，产率为91％。
1H NMR(600MHz,CDCl3)δ11.09(s,1H),10.74(s,1H),7.87–7.78(m,4H),7.47(d,J＝7.8Hz,2H),7.28(d,J＝7.6Hz,2H),7.15–7.00(m,5H),6.96(d,J＝6.9Hz,2H),6.75(d,J＝10.7Hz,2H),6.27(t,J＝7.4Hz,1H),2.38(s,3H).13C NMR(151MHz,DMSO)δ164.0,139.4,133.7,132.7,132.6,130.5,129.7,129.4,125.1,124.9,123.9,123.3,122.2,122.1,121.8,114.2,112.7,105.2,89.4,16.8.(ESI)计算值C30H23IN2O3S,[M+H]+619.0548，实际值619.0547。
实施例7
Figure BDA0002924773480000081
操作步骤同实施例1，得到产物3ha，产率为79％。
1H NMR(600MHz,CDCl3)δ10.97(s,1H),10.76(s,1H),7.80(d,J＝7.8Hz,2H),7.63(d,J＝8.1Hz,2H),7.32(d,J＝7.9Hz,2H),7.23(d,J＝8.1Hz,3H),7.09–6.96(m,5H),6.91(d,J＝7.5Hz,2H),6.75–6.68(m,2H),6.22(t,J＝7.6Hz,1H),2.51(s,3H),2.34(s,3H).13CNMR(151MHz,CDCl3)δ168.2,160.5,144.0,139.9,138.5,138.4,137.5,135.0,134.5,134.4,129.6,128.7,128.0,127.0,126.9,126.8,125.4,122.4,119.4,118.9,117.4,109.8,21.5,15.5.(ESI)计算值C31H26N2O3S2,[M+H]+539.1457，实际值539.1458。
实施例8
Figure BDA0002924773480000091
操作步骤同实施例1，得到产物3ia，产率为86％。
1H NMR(600MHz,CDCl3)δ10.98(s,1H),10.75(s,1H),7.81(d,J＝7.4Hz,2H),7.53–7.46(m,2H),7.24(m,3H),7.10–6.98(m,5H),6.92(d,J＝6.9Hz,2H),6.77–6.69(m,2H),6.24(t,J＝7.4Hz,1H),2.34–2.38(m,6H),2.33(s,3H).13C NMR(151MHz,CDCl3)δ168.3,160.5,139.4,138.5,137.8,137.6,137.5,134.9,134.5,134.5,130.5,129.6,128.7,127.9,127.8,127.0,126.7,126.3,122.6,122.3,119.6,118.9,117.4,109.8,21.5,19.9,19.7.(ESI)计算值C32H28N2O3S,[M+H]+521.1892，实际值521.1893。
实施例9
Figure BDA0002924773480000092
操作步骤同实施例1，得到产物3ja，产率为71％。
1H NMR(600MHz,CDCl3)δ10.94(s,1H),10.71(s,1H),7.82(d,J＝7.3Hz,2H),7.65(s,1H),7.46(s,2H),7.27(d,J＝8.2Hz,2H),7.00–7.10(m,5H),6.94(d,J＝6.6Hz,2H),6.75(d,J＝8.2Hz,1H),6.65(s,1H),6.25(t,J＝7.4Hz,1H),2.37(s,3H).13C NMR(151MHz,CDCl3)δ168.3,160.5,144.0,138.2,137.6,137.5,135.0,134.9,134.4,132.1,129.6,128.7,127.9,127.2,127.0,126.8,125.1,121.3,119.4,119.0,117.4,110.1,21.5.(ESI)计算值C28H22N2O3S2,[M+H]+499.1144，实际值499.1145。
实施例10
Figure BDA0002924773480000101
操作步骤同实施例1，得到产物3ka，产率为60％。
1H NMR(600MHz,CDCl3)δ10.82(s,1H),10.45(s,1H),7.85(d,J＝8.2Hz,2H),7.29(d,J＝8.2Hz,2H),7.09(d,J＝7.9Hz,1H),7.06–6.99(m,4H),6.98–6.94(m,2H),6.80–6.78(m,1H),6.73(d,J＝8.1Hz,1H),6.66(dd,J＝3.7,1.6Hz,1H),6.53(d,J＝2.7Hz,1H),6.29–6.22(m,2H),3.91(s,3H),2.39(s,3H).13C NMR(151MHz,CDCl3)δ167.4,165.3,160.2,143.9,138.4,137.8,134.7,134.5,134.4,132.4,129.6,128.8,127.9,127.0,126.7,125.8,124.5,122.0,119.7,118.9,117.4,110.9,110.5,108.8,35.9,21.5.(ESI)计算值C29H25N3O3S,[M+H]+496.1690，实际值496.1689。
实施例11
Figure BDA0002924773480000111
操作步骤同实施例1，得到产物3la，产率为58％。
1H NMR(600MHz,CDCl3)δ10.86(s,1H),10.64(s,1H),7.93(d,J＝8.0Hz,2H),7.34(d,J＝8.0Hz,2H),7.08(d,J＝7.8Hz,1H),6.99–7.06(m,6H),6.72(d,J＝8.2Hz,1H),6.50(d,J＝2.4Hz,1H),6.22(t,J＝7.5Hz,1H),4.74(s,2H),4.43(s,2H),4.23(s,5H),2.42(s,3H).13C NMR(151MHz,CDCl3)δ166.7,160.3,143.9,140.7,139.0,138.3,134.7,134.6,134.6,129.7,128.9,127.9,126.9,126.7,121.9,119.6,118.8,117.2,110.1,74.6,70.2,69.8,66.2,21.5.(ESI)计算值C34H28FeN2O3S,[M+H]+601.1242，实际值601.1243。
实施例12
Figure BDA0002924773480000112
操作步骤同实施例1，得到产物3ma，产率为66％。
1H NMR(600MHz,CDCl3)δ11.15(s,1H),10.75(s,1H),9.03(s,1H),8.61(d,J＝4.1Hz,1H),8.01(d,J＝7.8Hz,1H),7.85(d,J＝7.8Hz,2H),7.42(dd,J＝7.7,4.9Hz,1H),7.30(d,J＝7.9Hz,2H),7.17–6.98(m,7H),6.84(s,1H),6.75(d,J＝8.3Hz,1H),6.31(t,J＝7.6Hz,1H),2.39(s,3H).13C NMR(151MHz,CDCl3)δ169.1,149.2,146.6,144.3,137.4,135.4,134.8,134.0,131.8,129.7,128.6,128.1,127.0,126.9,126.7,123.9,119.0,117.5,110.1,21.5.(ESI)计算值C29H23N3O3S,[M+H]+494.1532，实际值494.1533。
实施例13
Figure BDA0002924773480000121
操作步骤同实施例1，得到产物3na，产率为76％。
1H NMR(600MHz,CDCl3)δ10.91(s,1H),10.44(s,1H),7.84(d,J＝8.1Hz,2H),7.29(d,J＝8.1Hz,2H),7.08(d,J＝7.8Hz,1H),6.96–7.04(m,4H),6.93–6.89(m,2H),6.72(d,J＝8.2Hz,1H),6.28(d,J＝2.8Hz,1H),6.23(t,J＝7.6Hz,1H),2.39(s,3H),1.47(s,9H).13CNMR(151MHz,CDCl3)δ167.3,159.4,149.9,142.9,136.9,136.9,133.9,133.7,133.7,128.6,127.9,126.8,125.9,125.4,119.6,118.6,117.8,116.2,107.8,31.2,29.0,20.5.(ESI)计算值C28H28N2O3S,[M+H]+473.1904，实际值473.1899。
实施例14
Figure BDA0002924773480000131
操作步骤同实施例1，得到产物3oa，产率为50％。
1H NMR(600MHz,CDCl3)δ11.79(s,1H),10.37(s,1H),7.77(d,J＝6.7Hz,2H),7.22(s,2H),7.15–7.00(m,7H),6.83(d,J＝7.7Hz,1H),6.46(t,J＝7.4Hz,1H),4.38(q,J＝6.9Hz,2H),2.37(s,3H),1.40(t,J＝6.9Hz,3H).13C NMR(151MHz,CDCl3)δ171.3,162.3,160.2,144.6,136.7,134.0,133.3,129.7,128.3,127.8,127.3,126.9,126.1,122.8,119.4,118.0,114.4,61.2,21.5,14.3.(ESI)计算值C27H24N2O5S,[M+H]+489.1483，实际值489.1479。
实施例15
Figure BDA0002924773480000132
操作步骤同实施例1，得到产物3pa，产率为66％。
1H NMR(600MHz,CDCl3)δ10.28(s,1H),9.93(s,1H),7.74(d,J＝7.8Hz,2H),7.16–7.26(m,3H),6.96(t,J＝7.3Hz,2H),6.91(dd,J＝11.6,7.2Hz,2H),6.86(d,J＝7.4Hz,1H),6.81(d,J＝7.2Hz,2H),6.59(d,J＝8.2Hz,1H),6.15(t,J＝7.3Hz,1H),2.74(q,J＝7.6Hz,2H),2.35(s,3H),1.92(s,3H),1.36(t,J＝7.6Hz,3H).13C NMR(151MHz,CDCl3)δ167.0,143.5,141.7,138.2,137.8,134.2,133.7,130.0,129.5,127.6,126.9,126.3,122.3,119.0,118.7,117.3,21.5,19.9,12.4,9.5.(ESI)计算值C27H26N2O3S,[M+H]+459.1740，实际值459.1737。
实施例16
(1)
Figure BDA0002924773480000141
操作步骤同实施例1，得到产物3qa，产率为65％。
(2)
Figure BDA0002924773480000142
将取10mL的反应管，将称量好的肟酯类化合物1r(0.12mmol)、苯并呋喃亚胺类化合物2a(0.1mmol)、CuI(0.02mmol)加入其中，然后在惰性气体保护下，加入DMSO/1,4-Dioxane(1mL)后，将反应管用聚四氟乙烯的塞子密封。将反应管置于80℃的油浴锅中搅拌10小时，反应完毕后，降至室温，用(20mL×3)乙酸乙酯萃取三次，40mL饱和食盐水洗涤，合并有机相，旋转蒸发去除溶剂得到含有3qa的混合物，然后快速柱层析得产物3qa，收率42/79％。
1H NMR(600MHz,CDCl3)δ10.27(s,1H),10.22(s,1H),7.76(d,J＝7.4Hz,2H),7.65(d,J＝7.6Hz,2H),7.44(t,J＝7.5Hz,2H),7.34(t,J＝7.3Hz,1H),7.20(d,J＝7.8Hz,2H),7.02–6.86(m,5H),6.83(d,J＝7.3Hz,2H),6.58(d,J＝8.2Hz,1H),6.22(t,J＝7.5Hz,1H),2.52(d,J＝7.0Hz,2H),2.31(s,3H),1.25(m,1.20–1.28,1H),0.42(d,J＝6.5Hz,6H).13CNMR(151MHz,DMSO)δ164.0,139.0,133.3,132.8,132.7,129.7,129.6,127.4,125.4,124.9,124.3,123.8,123.0,123.0,122.3,121.8,118.8,118.4,117.2,115.3,114.3,112.7,28.6,23.9,17.4,16.8.(ESI)计算值C34H32N2O3S,[M+H]+549.2206，实际值549.2208。
实施例17
Figure BDA0002924773480000151
操作步骤同实施例1，得到产物3ab，产率为97％。
1H NMR(600MHz,CDCl3)δ11.00(s,1H),10.77(s,1H),7.81(d,J＝8.0Hz,2H),7.75(d,J＝7.6Hz,2H),7.49(t,J＝7.6Hz,2H),7.39(t,J＝7.3Hz,1H),7.26–7.23(m,2H),7.10(dd,J＝14.4,7.2Hz,2H),6.96(t,J＝7.9Hz,1H),6.79–6.74(m,2H),6.61–6.54(m,2H),6.42(s,1H),6.30(t,J＝7.6Hz,1H),3.63(s,3H),2.36(s,3H).13C NMR(151MHz,CDCl3)δ168.7,160.5,159.1,144.1,138.7,137.9,137.4,135.7,135.2,134.3,130.3,129.6,129.3,129.0,128.8,127.0,125.1,121.3,119.1,117.4,113.8,113.2,109.8,55.1,21.5.(ESI)计算值C31H26N2O4S,[M+H]+523.1686，实际值523.1686。
实施例18
Figure BDA0002924773480000161
操作步骤同实施例1，得到产物3ac，产率为93％。
1H NMR(600MHz,CDCl3)δ11.08(s,1H),10.73(s,1H),7.82(d,J＝8.0Hz,2H),7.74(d,J＝7.6Hz,2H),7.48(t,J＝7.6Hz,2H),7.38(t,J＝7.3Hz,1H),7.26–7.23(m,2H),7.11(d,J＝7.8Hz,1H),7.08(t,J＝7.6Hz,1H),6.79–6.88(m,4H),6.72–6.77(m,2H),6.27(t,J＝7.5Hz,1H),2.36(s,3H),2.18(s,3H).13C NMR(151MHz,CDCl3)δ168.8,160.7,144.0,138.7,138.1,137.5,136.4,134.9,134.6,131.4,130.4,129.6,129.3,128.7,128.6,127.0,125.0,122.3,119.4,119.0,117.5,109.8,21.5,21.0.(ESI)计算值C31H26N2O3S,[M+H]+507.1736，实际值507.1737。
实施例19
Figure BDA0002924773480000162
操作步骤同实施例1，得到产物3ad，产率为82％。
1H NMR(600MHz,CDCl3)δ10.35–11.00(m,2H),7.74(d,J＝7.7Hz,2H),7.66(d,J＝7.6Hz,2H),7.42(t,J＝7.5Hz,2H),7.32(t,J＝7.2Hz,1H),7.21–7.17(m,2H),7.09(d,J＝8.3Hz,2H),7.06(d,J＝7.4Hz,1H),6.98(d,J＝6.9Hz,1H),6.75(d,J＝8.1Hz,2H),6.70(d,J＝8.3Hz,1H),6.66(d,J＝2.0Hz,1H),6.25(t,J＝7.5Hz,1H),2.30(s,3H).13C NMR(151MHz,CDCl3)δ167.3,143.2,137.8,136.4,135.4,134.3,133.1,132.4,130.1,129.2,128.7,128.3,127.8,126.0,124.1,121.5,120.0,118.2,116.7,108.7,20.5.(ESI)计算值C30H23BrN2O3S,[M+H]+571.0688，实际值571.0686。
实施例20
Figure BDA0002924773480000171
操作步骤同实施例1，得到产物3ae，产率为83％。
1H NMR(600MHz,CDCl3)δ10.45–11.50(m,2H),7.83(d,J＝7.0Hz,2H),7.73(d,J＝7.7Hz,2H),7.50(t,J＝7.5Hz,2H),7.41(t,J＝7.1Hz,1H),7.33(d,J＝7.8Hz,2H),7.29(d,J＝7.7Hz,2H),7.14(t,J＝7.5Hz,1H),7.08(d,J＝7.8Hz,2H),7.03(s,1H),6.78(d,J＝8.4Hz,2H),6.31(t,J＝7.5Hz,1H),2.39(s,3H).13C NMR(151MHz,CDCl3)δ168.0,144.4,139.3,138.9,137.3,135.6,133.9,131.7,129.9,129.7,129.4,129.1,129.0,127.0,125.1,119.2,118.7,117.8,110.2,109.7,21.5.(ESI)计算值C31H23N3O3S,[M+H]+518.1531，实际值518.1533。
实施例21
Figure BDA0002924773480000181
操作步骤同实施例1，得到产物3af，产率为89％。1H NMR(600MHz,CDCl3)δ10.92(s,1H),10.42(s,1H),7.84(d,J＝7.2Hz,2H),7.75(d,J＝7.5Hz,2H),7.49(t,J＝7.6Hz,2H),7.39(t,J＝7.4Hz,1H),7.29(d,J＝7.8Hz,2H),7.08(d,J＝5.9Hz,1H),7.01(t,J＝7.4Hz,1H),6.95–6.87(m,3H),6.84(d,J＝6.9Hz,1H),6.70(d,J＝2.2Hz,1H),6.66(d,J＝8.2Hz,1H),6.29(t,J＝7.3Hz,1H),2.41(s,3H),2.18(s,3H).13C NMR(151MHz,CDCl3)δ167.8,143.9,139.1,138.1,137.9,135.7,134.5,134.2,130.6,130.2,129.8,129.7,129.3,128.8,127.2,127.0,125.3,125.2,124.4,119.8,118.7,117.4,111.8,21.5,20.0.(ESI)计算值C31H26N2O3S,[M+H]+507.1732，实际值507.1737。
实施例22
Figure BDA0002924773480000182
操作步骤同实施例1，得到产物3ag，产率为87％。
1H NMR(600MHz,CDCl3)δ12.28(s,1H),10.57(s,1H),7.78(d,J＝8.0Hz,2H),7.74(d,J＝7.7Hz,2H),7.49(t,J＝7.5Hz,2H),7.38(t,J＝7.4Hz,1H),7.22(d,J＝7.9Hz,2H),7.10–7.01(m,4H),6.91(d,J＝7.6Hz,2H),6.74(s,1H),6.25(s,1H),5.85(d,J＝9.1Hz,1H),3.67(s,3H),2.32(s,3H).13C NMR(151MHz,CDCl3)δ168.3,166.1,164.7,143.9,137.5,137.5,136.7,135.9,134.4,130.6,129.5,129.3,129.0,128.4,128.0,127.0,126.6,124.8,121.5,112.3,108.8,107.7,100.7,55.4,21.5.(ESI)计算值C31H26N2O4S,[M+H]+523.1682，实际值523.1686。
实施例23
Figure BDA0002924773480000191
操作步骤同实施例1，得到产物3ah，产率为92％。
1H NMR(600MHz,CDCl3)δ11.14(s,1H),10.75(s,1H),7.86(d,J＝8.8Hz,2H),7.75(d,J＝7.4Hz,2H),7.49(t,J＝7.7Hz,2H),7.39(t,J＝7.4Hz,1H),7.13–7.08(m,1H),7.08–6.99(m,4H),6.96–6.93(m,2H),6.91(d,J＝8.9Hz,2H),6.73–6.78(m,2H),6.27(t,J＝7.6Hz,1H),3.80(s,3H).13C NMR(151MHz,DMSO)δ163.9,158.6,156.0,133.8,133.0,130.4,129.7,129.6,127.2,125.6,124.6,124.5,124.0,123.3,122.0,120.3,117.6,114.6,114.2,112.7,109.5,105.0,50.9.(ESI)计算值C30H24N2O4S,[M+H]+509.1527，实际值509.1530。
实施例24
Figure BDA0002924773480000201
操作步骤同实施例1，得到产物3ai，产率为59％。
1H NMR(600MHz,CDCl3)δ10.65(s,1H),10.25(s,1H),8.07(d,J＝8.0Hz,2H),7.69–7.79(m,4H),7.51(t,J＝7.7Hz,2H),7.42(t,J＝7.4Hz,1H),7.12–7.00(m,5H),6.97(d,J＝7.3Hz,2H),6.79(d,J＝2.6Hz,1H),6.74(d,J＝8.1Hz,1H),6.30(t,J＝7.4Hz,1H).13C NMR(151MHz,CDCl3)δ167.6,158.7,143.1,138.7,138.4,134.2,133.1,129.0,128.4,128.1,127.7,127.0,126.5,125.9,125.1,125.1,124.2,122.0,121.2,118.7,118.4,116.6,109.8.19F NMR(565MHz,CDCl3)δ-63.19.(ESI)计算值C30H21F3N2O3S,[M+H]+547.1298，实际值547.1298。
实施例25
Figure BDA0002924773480000202
操作步骤同实施例1，得到产物3aj，产率为85％。
1H NMR(600MHz,CDCl3)δ11.07(s,1H),10.69(s,1H),7.94(d,J＝7.3Hz,1H),7.74(d,J＝7.6Hz,2H),7.49(t,J＝7.7Hz,2H),7.40(q,J＝7.8Hz,2H),7.32(d,J＝7.5Hz,1H),7.20(t,J＝7.3Hz,1H),7.14–7.10(m,1H),7.09–7.04(m,3H),7.02(d,J＝6.9Hz,1H),6.99(d,J＝7.0Hz,2H),6.77–6.72(m,2H),6.27(t,J＝7.6Hz,1H),2.80(s,3H).13C NMR(151MHz,CDCl3)δ168.9,138.5,138.4,137.4,135.1,134.4,133.2,132.5,130.3,129.3,128.7,128.7,128.5,128.0,126.8,126.1,125.0,119.0,117.6,109.9,20.7.(ESI)计算值C30H24N2O3S,[M+H]+493.1580，实际值493.1580。

Claims (7)

1.一种吡咯类化合物的合成方法，其特征在于，包括以下步骤：
取肟酯类化合物1、苯并呋喃亚胺类化合物2、一价铜化合物，惰性保护气体下加入有机溶剂，60-120 oC条件下反应，TLC监测反应进程，反应完毕后，降至室温，乙酸乙酯萃取后用饱和食盐水洗涤，合并有机相，旋转蒸发去除溶剂得粗品，快速柱层析，得吡咯类化合物3；
其反应式为：
Figure 372001DEST_PATH_IMAGE002
其中，R1为芳基、烷基或酯基； R2为H或烷基；R3为H或甲氧基；R4为芳基；R5为氰基、卤素、烷基或烷氧基。
2.根据权利要求1所述的方法，其特征在于：所述肟酯类化合物1与苯并呋喃亚胺类化合物2的摩尔比为1:1.2。
3.根据权利要求1所述的方法，其特征在于：反应时间为16小时。
4.根据权利要求1所述的方法，其特征在于：所述萃取为乙酸乙酯萃取3次。
5.根据权利要求1所述的方法，其特征在于：所述一价铜化合物为CuCl、CuBr、CuI或CuOAc。
6.根据权利要求1所述的方法，其特征在于：所述有机溶剂为二甲基亚砜、四氢呋喃、1,4-二氧六环、甲苯、N,N-二甲基酰胺、1,2-二氯乙烷、二氯甲烷。
7.根据权利要求1所述的方法，其特征在于：所述惰性保护气体为氩气。
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