CN114524790A - C2位炔基化双取代2h-色烯化合物及其制备方法 - Google Patents
C2位炔基化双取代2h-色烯化合物及其制备方法 Download PDFInfo
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- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
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- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07F7/0803—Compounds with Si-C or Si-Si linkages
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- C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
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Abstract
本发明公开了一类C2位炔基化双取代2H‑色烯化合物,属于有机合成技术领域,该类化合物的制备方法是在空气氛围下,通过添加催化剂氯化铜,将2H‑色烯半缩酮和末端炔烃溶于有机溶剂1,4‑二氧六环,在90℃条件下搅拌反应,反应结束后减压蒸出溶剂,柱层析分离提纯,最终得到一系列2‑炔基‑2,2‑双取代‑2H‑色烯化合物;本发明提供了一类结构新颖的同时含有2H‑色烯及膦酰基取代基的多官能团化的化合物,可以为新药的研发、药物的筛选以及农药研究提供更多候选分子,其在抗肿瘤、抗炎等药物研究及农药中具有很好的潜在价值,且本发明的制备方法所用的原料方便制备,反应副产物为水,具有原子经济性高、绿色环保等优点。
Description
技术领域
本发明涉及有机化合物合成技术领域,尤其涉及一类C2位炔基化双取代2H-色烯化合物及其制备方法。
背景技术
色烯类化合物具有苯并吡喃结构,色烯及其衍生物广泛存在于各种植物中,具有多种优秀的生理活性,例如:2H-色烯化合物对几种常见食源性致病菌有良好的抑制效果,同时还可应用于抗癌、降血糖等方面的研究。色烯类化合物还具有特殊的荧光性质,在生物、材料等领域起着重要作用。色烯结构是许多天然产物的核心骨架,并且这类化合物合成方法简便,原料廉价易得,在医药、化工等领域具有巨大的发展潜力。
炔类化合物广泛分布于菊科、檀香科等植物中,研究表明,炔烃类化合物中的不饱和三键具有很高的化学活性,炔基官能团是许多药物、天然产物的重要结构单元。在医药领域,炔基是许多药物的重要功能基团,例如:抗艾滋病病毒的特效药依法韦仑就是一种小分子炔类化合物。自然界中存在的炔类天然产物也具有多种生物活性,例如:从细菌中分离出的烯二炔类抗生素对肿瘤细胞有较好的抑制效果,从伞形科植物中提取的聚炔化合物具有抗炎、抗菌等活性。另外,炔类化合物在农业生产方面已得到广泛应用,是一类高效的除草剂,也可用于防治作物病害。
向苯、呋喃、吡喃等结构中引入炔基,可以使活泼的碳碳三键变得更稳定。目前,在2H-色烯化合物C2位引入炔基官能团,合成C2位炔基化双取代2H-色烯化合物的方法尚无报道。而具有这类结构的化合物,可预期作为药物筛选的候选化合物。
发明内容
本发明的目的之一,就在于提供一类结构新颖的C2位炔基化双取代2H-色烯化合物,以解决上述问题。
为了实现上述目的,本发明采用的技术方案是这样的:C2位炔基化双取代2H-色烯化合物,其具有如下式所示的结构,
式中,R1选自氢,6-叔丁基,6-甲基或7-氯取代基中的一种;
R2选自氢,2-萘,3-溴,3-甲氧基,4-氯,4-甲基或4-甲氧基中的一种;
R3选自取代芳基或甲酸甲酯取代基中的一种;
R4选自正丁基,环丙烷基,三甲基硅或取代芳基中的一种。
作为优选的技术方案:R3的取代芳基的取代基选自氢,2-氯、甲氧基,3-氯、氟、甲氧基,4-氟、氯、溴、甲基、甲氧基,1-萘或2-萘中的至少一种;
R4的取代芳基的取代基选自氢、2-氯取代基,3-硝基、甲氧基或4-氟、三氟甲基、氯、溴、甲基、甲氧基中的至少一种。
本发明提供了一类新颖的含有苯并吡喃及炔基结构的化合物,可以为新药的研发、药物的筛选以及农药研究等提供更多候选分子和先导化合物,其在抗肿瘤、抗炎等药物研究及农药中具有很好的潜在价值。
本发明的目的之二,在于提供一种上述的C2位炔基化双取代2H-色烯化合物的制备方法,包括下述步骤:将2H-色烯半缩酮与氯化铜溶于有机溶剂中,再加入末端炔烃,反应完毕后减压蒸出溶剂,经柱层析分离提纯,即得。
作为优选的技术方案:所述末端炔烃的摩尔量为2H-色烯半缩酮摩尔量的1~3倍,优选为2.5倍。
作为优选的技术方案:所述氯化铜的摩尔量为2H-色烯半缩酮摩尔量的0.1~0.2倍,优选为0.1倍。
作为优选的技术方案:所述有机溶剂的体积用量为2H-色烯半缩酮摩尔量的10倍。
作为优选的技术方案:所述有机溶剂选自1,4-二氧六环、乙酸乙酯、四氢呋喃、乙二醇二甲醚、二氯甲烷、1,2-二氯乙烷、1,1,2-三氯丙烷中的一种,优选1,4-二氧六环。
作为优选的技术方案:反应温度为60~120℃,优选90℃。
作为优选的技术方案:反应时间为1.5~24小时。
为了获得最佳的反应收率,发明人做了单因素对比实验,对反应的溶剂、温度、催化剂用量以及苯乙炔用量等反应条件的考察,具体见表1和表2。
表1、溶剂考察
表2、反应温度,催化剂用量以及金苯乙炔用量考察
从上表可以看出,溶剂采用1,4-二氧六环、反应温度90℃、反应时间1.5h、催化剂用量0.1倍、末端炔烃2.5倍,为最佳实施例。
与现有技术相比,本发明的优点在于:
(1)本发明所制得的化合物是一类同时含有2H-色烯及膦酰基取代基的多官能团化的化合物,丰富了药物筛选化合物库,可以为新药的研发、药物的筛选以及农药研究提供更多候选分子和先导化合物,其在抗肿瘤、抗炎等药物以及农药研究中具有很好的潜在应用价值;
(2)本发明的方法所使用的原料和试剂原料易得,都可由商业可得的原料方便地制备,成本低廉;
(3)本发明方法所使用的各种原料在常温下可方便地存放,无需严格的特殊处理,可方便管理,且安全性高;
(4)本发明方法的条件温和、操作方便,对底物中的各种官能团的兼容性高,底物适用范围广;反应迅速,避免了时间和能源的消耗,合成效率高;
(5)本发明唯一的副产物为水,反应原子经济性高、绿色环保。
附图说明
图1为实施例1制得的化合物的氢谱图;
图2为实施例1制得的化合物的碳谱图;
图3为实施例1制得的化合物的质谱图。
具体实施方式
下面结合附图对本发明的技术方案进行清楚、完整地描述,所描述的实施例是本发明部分实施例,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做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。
下述实施例中所使用的2H-色烯半缩酮可以通过现有技术制备得到(参考M.Terada,T.Yamanaka and Y.Toda,Chemical Engineering Journal.,2013,19,13658)。
下述实施例中所使用的末端炔烃、催化剂、溶剂等均通过市售购买获得。
本发明系列C2位炔基化双取代2H-色烯化合物的合成通式如下:
实施例1:2,4-二苯基-2-(苯乙炔基)-2H-色烯的合成
在空气氛围下,向10.0mL的玻璃瓶中加入2,4-二苯基-2H-色烯半缩酮(90.1mg,0.3mmol),无水氯化铜(4.0mg,0.03mmol),干燥的1,4-二氧六环3mL,苯乙炔(76.6mg,0.75mmol),加热至90℃,搅拌反应,TLC追踪反应情况,待原料消失完全后停止反应。冷却至室温,减压蒸馏除去溶剂,柱层析分离提纯产物,淋洗剂为石油醚,得到淡黄色黏稠液体,即为产物2,4-二苯基-2-(苯乙炔基)-2H-色烯,产率为83%;1H NMR(400MHz,CDCl3):δ=7.88-7.86(m,2H),7.46-7.35(m,10H),7.29-7.24(m,3H),7.23-7.19(m,1H),7.12-7.09(m,1H),7.04-7.02(d,J=8.4Hz,1H),6.92-6.88(m,1H),5.92(s,1H);13C{1H}NMR(150MHz,CDCl3):δ=152.5,142.0,137.6,135.7,131.9,129.8,128.8,128.7,128.5,128.46,128.4,128.2,128.1,126.6,125.9,124.9,122.3,121.8,121.5,117.2,88.1,88.08,76.1;HRMS(ESI):Exact mass calcd for C28H20O[M+H]+:385.1587,Found:385.1584:其核磁氢谱、碳谱、质谱图分别如图1,图2和图3所示。
实施例2:2,4-二苯基-2-(正己炔基)-2H-色烯的合成
在空气氛围下,向10.0mL的玻璃瓶中加入2,4-二苯基-2H-色烯半缩酮(90.1mg,0.3mmol),无水氯化铜(4.0mg,0.03mmol),干燥的1,4-二氧六环3mL,正己炔(60.2mg,0.75mmol),加热至90℃,搅拌反应,TLC追踪反应情况,待原料消失完全后停止反应。冷却至室温,减压蒸馏除去溶剂,柱层析分离提纯产物,淋洗剂为石油醚,得到淡黄色黏稠液体,即为产物2,4-二苯基-2-(正己炔基)-2H-色烯,产率为70%;1H NMR(600MHz,CDCl3):δ=7.81-7.79(m,2H),7.43-7.38(m,7H),7.34-7.32(m,1H),7.22-7.19(m,1H),7.09-7.08(m,1H),7.00-6.99(m,1H),6.90-6.88(m,1H),5.84(s,1H),2.29-2.27(m,2H),1.50-1.46(m,2H),1.38-1.32(m,2H),0.86(t,J=7.2Hz,3H);13C{1H}NMR(150MHz,CDCl3):δ=152.7,142.4,137.8,135.2,129.6,128.9,128.45,128.39,128.0,126.7,125.9,122.0,121.4,117.2,89.7,79.5,76.0,30.6,21.9,18.8,13.6;HRMS(ESI):Exact mass calcd for C27H24O[M+H]+:365.1900,Found:365.1900。
实施例3:2,4-二苯基-2-(环丙基乙炔)-2H-色烯的合成
在空气氛围下,向10.0mL的玻璃瓶中加入2,4-二苯基-2H-色烯半缩酮(90.1mg,0.3mmol),无水氯化铜(4.0mg,0.03mmol),干燥的1,4-二氧六环3mL,环丙基乙炔(49.6mg,0.75mmol),加热至90℃,搅拌反应,TLC追踪反应情况,待原料消失完全后停止反应。冷却至室温,减压蒸馏除去溶剂,柱层析分离提纯产物,淋洗剂为石油醚,得到淡黄色黏稠液体,即为产物2,4-二苯基-2-(环丙基乙炔)-2H-色烯,产率为75%;1H NMR(600MHz,CDCl3):δ=7.77-7.75(m,2H),7.42-7.37(m,7H),7.33-7.31(m,1H),7.21-7.18(m,1H),7.08(dd,J=7.8Hz,1.8Hz,1H),6.99-6.97(m,1H),6.89(td,J=7.8Hz,1.2Hz,1H),5.81(s,1H),1.33-1.30(m,1H),0.80-0.77(m,2H),0.72-0.70(m,2H);13C{1H}NMR(150MHz,CDCl3):δ=152.6,142.5,137.8,135.1,129.7,128.9,128.45,128.39,128.1,126.6,125.9,125.6,121.8,121.4,117.2,92.6,75.9,74.5,8.7,0.1;HRMS(ESI):Exact mass calcd for C26H20O[M+H]+:349.1587,Found:349.1588。
实施例4:2,4-二苯基-2-(三甲基硅乙炔)-2H-色烯的合成
在空气氛围下,向10.0mL的玻璃瓶中加入2,4-二苯基-2H-色烯半缩酮(90.1mg,0.3mmol),无水氯化铜(4.0mg,0.03mmol),干燥的1,4-二氧六环3mL,三甲基硅乙炔(73.7mg,0.75mmol),加热至90℃,搅拌反应,TLC追踪反应情况,待原料消失完全后停止反应。冷却至室温,减压蒸馏除去溶剂,柱层析分离提纯产物,淋洗剂为石油醚和乙酸乙酯,体积比为200:1,得到淡黄色黏稠液体,即为产物2,4-二苯基-2-(三甲基硅乙炔)-2H-色烯,产率为52%;1H NMR(600MHz,CDCl3):δ=7.79-7.78(m,2H),7.43-7.42(m,4H),7.41-7.40(m,1H),7.39-7.38(m,2H),7.35-7.34(m,1H),7.21-7.18(m,1H),7.08(dd,J=7.8Hz,1.2Hz,1H),6.99-6.97(m,1H),6.90-6.87(m,1H),5.83(s,1H),0.17(s,9H);13C{1H}NMR(150MHz,CDCl3):δ=152.5,141.8,137.7,135.6,129.7,128.9,128.6,128.48,128.46,128.1,126.7,125.9,125.0,121.8,121.4,117.2,104.1,93.4,76.1,0.1;HRMS(ESI):Exact masscalcd for C26H24OSi[M+H]+:381.1669,Found:381.1670。
实施例5:2,4-二苯基-2-(对甲苯乙炔)-2H-色烯的合成
在空气氛围下,向10.0mL的玻璃瓶中加入2,4-二苯基-2H-色烯半缩酮(90.1mg,0.3mmol),无水氯化铜(4.0mg,0.03mmol),干燥的1,4-二氧六环3mL,对甲苯乙炔(87.1mg,0.75mmol),加热至90℃,搅拌反应,TLC追踪反应情况,待原料消失完全后停止反应。冷却至室温,减压蒸馏除去溶剂,柱层析分离提纯产物,淋洗剂为石油醚和乙酸乙酯,体积比为200:1,得到淡黄色黏稠液体,即为产物2,4-二苯基-2-(对甲苯乙炔)-2H-色烯,产率为71%;1H NMR(600MHz,CDCl3):δ=7.88(ABd,J=7.2Hz,2H),7.47-7.42(m,7H),7.41-7.39(m,1H),7.34(ABd,J=7.8Hz,2H),7.24-7.21(m,1H),7.13-7.10(m,3H),7.04(d,J=8.4Hz,1H),6.92-6.90(m,1H),5.93(s,1H),2.34(s,3H);13C{1H}NMR(150MHz,CDCl3):δ=152.5,142.1,138.8,137.6,135.6,131.8,129.7,129.0,128.8,128.5,128.43,128.39,128.0,126.6,125.9,125.1,121.8,121.4,119.2,117.2,88.4,87.5,76.2,21.5;HRMS(ESI):Exactmass calcd for C30H22O[M+H]+:399.1743,Found:399.1744。
实施例6:2,4-二苯基-2-(间甲氧基苯乙炔)-2H-色烯的合成
在空气氛围下,向10.0mL的玻璃瓶中加入2,4-二苯基-2H-色烯半缩酮(90.1mg,0.3mmol),无水氯化铜(4.0mg,0.03mmol),干燥的1,4-二氧六环3mL,间甲氧基苯乙炔(99.1mg,0.75mmol),加热至90℃,搅拌反应,TLC追踪反应情况,待原料消失完全后停止反应。冷却至室温,减压蒸馏除去溶剂,柱层析分离提纯产物,淋洗剂为石油醚和乙酸乙酯,体积比为200:1,得到无色黏稠液体,即为产物2,4-二苯基-2-(间甲氧基苯乙炔)-2H-色烯,产率为67%;1H NMR(600MHz,CDCl3):δ=7.88-7.86(m,2H),7.47-7.42(m,7H),7.41-7.37(m,2H),7.23-7.19(m,2H),7.13-7.11(m,1H),7.05-7.03(m,2H),6.97-6.96(m,1H),6.92(td,J=7.8Hz,1.2Hz,1H),6.88(dd,J=8.4Hz,3.0Hz,1H),5.93(s,1H),3.78(s,3H);13C{1H}NMR(150MHz,CDCl3):δ=159.2,152.5,142.0,137.6,135.7,129.8,129.3,128.8,128.53,128.47,128.4,128.1,126.6,126.0,124.9,124.5,123.3,121.8,121.5,117.2,116.6,115.3,88.04,87.96,76.2,55.3;HRMS(ESI):Exact mass calcd for C30H22O2[M+H]+:415.1693,Found:415.1694。
实施例7:2,4-二苯基-2-(邻氯苯乙炔)-2H-色烯的合成
在空气氛围下,向10.0mL的玻璃瓶中加入2,4-二苯基-2H-色烯半缩酮(90.1mg,0.3mmol),无水氯化铜(4.0mg,0.03mmol),干燥的1,4-二氧六环3mL,邻氯苯乙炔(99.1mg,0.75mmol),加热至90℃,搅拌反应,TLC追踪反应情况,待原料消失完全后停止反应。冷却至室温,减压蒸馏除去溶剂,柱层析分离提纯产物,淋洗剂为石油醚,得到无色黏稠液体,即为产物2,4-二苯基-2-(邻氯苯乙炔)-2H-色烯,产率为59%;1H NMR(600MHz,CDCl3):δ=7.93-7.91(m,2H),7.46-7.42(m,7H),7.41-7.36(m,3H),7.25-7.22(m,2H),7.19-7.16(m,1H),7.13-7.12(m,1H),7.06-7.04(m,1H),6.93(td,J=7.8Hz,1.2Hz,1H),5.94(s,1H);13C{1H}NMR(150MHz,CDCl3):δ=152.5,141.6,137.6,136.4,136.0,133.4,129.8,129.6,129.2,128.9,128.6,128.5,128.4,128.1,126.8,126.3,126.0,124.9,122.4,122.0,121.6,117.3,93.1,85.1,76.3;HRMS(ESI):Exact mass calcd for C29H19ClO[M+H]+:419.1197,Found:419.1199。
实施例8:2-(对溴苯基)-4-苯基-2-(苯乙炔基)-2H-色烯的合成
在空气氛围下,向10.0mL的玻璃瓶中加入2-(对溴苯基)-4-苯基-2H-色烯半缩酮(113.8mg,0.3mmol),无水氯化铜(4.0mg,0.03mmol),干燥的1,4-二氧六环3mL,苯乙炔(76.6mg,0.75mmol),加热至90℃,搅拌反应,TLC追踪反应情况,待原料消失完全后停止反应。冷却至室温,减压蒸馏除去溶剂,柱层析分离提纯产物,淋洗剂为石油醚,得到无色黏稠液体,即为产物2-(对溴苯基)-4-苯基-2-(苯乙炔基)-2H-色烯,产率为52%;1H NMR(600MHz,CDCl3):δ=7.75-7.73(m,2H),7.56-7.54(m,2H),7.44-7.41(m,7H),7.33-7.28(m,3H),7.23(td,J=7.8Hz,1.2Hz,1H),7.11(dd,J=7.8Hz,1.2Hz,1H),7.03(d,J=7.8Hz,1H),6.92(td,J=7.8Hz,1.2Hz,1H),5.89(s,1H);13C{1H}NMR(150MHz,CDCl3):δ=152.2,141.1,137.4,136.1,131.9,131.6,129.9,128.8,128.45,128.4,128.24,128.20,126.0,124.3,122.7,122.0,121.7,117.1,88.3,87.7,75.6;HRMS(ESI):Exact mass calcd forC29H19BrO[M+H]+:463.0692,Found:463.0692。
实施例9:2-(间氟苯基)-4-苯基-2-(苯乙炔基)-2H-色烯的合成
在空气氛围下,向10.0mL的玻璃瓶中加入2-(间氟苯基)-4-苯基-2H-色烯半缩酮(95.6mg,0.3mmol),无水氯化铜(4.0mg,0.03mmol),干燥的1,4-二氧六环3mL,苯乙炔(76.6mg,0.75mmol),加热至90℃,搅拌反应,TLC追踪反应情况,待原料消失完全后停止反应。冷却至室温,减压蒸馏除去溶剂,柱层析分离提纯产物,淋洗剂为石油醚,得到无色黏稠液体,即为产物2-(间氟苯基)-4-苯基-2-(苯乙炔基)-2H-色烯,产率为68%;1H NMR(600MHz,CDCl3):δ=7.66-7.64(m,1H),7.60-7.57(m,1H),7.46-7.44(m,6H),7.42-7.41(m,1H),7.40-7.39(m,1H),7.33-7.29(m,3H),7.25-7.23(m,1H),7.13-7.12(m,1H),7.08-7.04(m,2H),6.95-6.92(m,1H),5.90(s,1H);13C{1H}NMR(150MHz,CDCl3):δ=162.7(d,JC-F=244.5Hz),152.4,144.6(d,JC-F=7.5Hz),137.4,126.0,131.9,130.0(d,JC-F=7.5Hz),129.9,128.8,128.4,128.24,128.2,126.1,124.3,122.2(d,JC-F=3.0Hz),121.71,121.67,117.1,115.4(d,JC-F=21.0Hz),113.9(d,JC-F=22.5Hz),88.3,87.6,75.6;19F{1H}NMR(564MHz,CDCl3):δ=-112.2;HRMS(ESI):Exact mass calcd for C29H19FO[M+H]+:403.1493,Found:403.1493。
实施例10:2-(邻甲氧基苯基)-4-苯基-2-(苯乙炔基)-2H-色烯的合成
在空气氛围下,向10.0mL的玻璃瓶中加入2-(邻甲氧基苯基)-4-苯基-2H-色烯半缩酮(99.1mg,0.3mmol),无水氯化铜(4.0mg,0.03mmol),干燥的1,4-二氧六环3mL,苯乙炔(76.6mg,0.75mmol),加热至90℃,搅拌反应,TLC追踪反应情况,待原料消失完全后停止反应。冷却至室温,减压蒸馏除去溶剂,柱层析分离提纯产物,淋洗剂为石油醚,得到无色黏稠液体,即为产物2-(邻甲氧基苯基)-4-苯基-2-(苯乙炔基)-2H-色烯,产率为59%;1H NMR(600MHz,CDCl3):δ=7.85-7.84(m,1H),7.43-7.37(m,8H),7.33(td,J=7.8Hz,1.2Hz,1H),7.28-7.26(m,2H),7.24-7.21(m,1H),7.13-7.11(m,1H),7.07(dd,J=7.8Hz,1.2Hz,1H),7.01-6.99(m,2H),6.90-6.88(m,1H),6.20(s,1H),3.91(s,3H);13C{1H}NMR(150MHz,CDCl3):δ=157.0,152.8,138.1,134.1,131.8,129.6,129.3,128.9,128.3,128.1,127.8,127.2,125.8,124.9,122.8,122.0,121.3,120.4,117.0,112.4,88.7,86.0,74.4,55.9;HRMS(ESI):Exact mass calcd for C30H22O2[M+H]+:415.1693,Found:415.1694。
实施例11:2-(1-萘)-4-苯基-2-(苯乙炔基)-2H-色烯的合成
在空气氛围下,向10.0mL的玻璃瓶中加入2-(1-萘)-4-苯基-2H-色烯半缩酮(105.1mg,0.3mmol),无水氯化铜(4.0mg,0.03mmol),干燥的1,4-二氧六环3mL,苯乙炔(76.6mg,0.75mmol),加热至90℃,搅拌反应,TLC追踪反应情况,待原料消失完全后停止反应。冷却至室温,减压蒸馏除去溶剂,柱层析分离提纯产物,淋洗剂为石油醚,得到无色固体,即为产物2-(1-萘)-4-苯基-2-(苯乙炔基)-2H-色烯,产率为66%,熔点:59-61℃;1HNMR(600MHz,CDCl3):δ=8.94(d,J=9.0Hz,1H),8.17-8.16(m,1H),7.90-7.87(m,2H),7.56-7.534(m,1H),7.527-7.51(m,3H),7.50-7.47(m,1H),7.46-7.43(m,2H),7.41-7.40(m,3H),7.30-7.26(m,3H),7.22-7.18(m,2H),7.03-7.01(m,1H),6.95-6.92(m,1H),6.15(s,1H);13C{1H}NMR(150MHz,CDCl3):δ=152.6,137.7,136.3,135.7,134.8,131.8,130.7,130.2,129.7,128.85,128.82,128.6,128.4,128.2,128.1,126.6,126.1,125.9,125.8,125.6,125.3,124.7,122.4,122.3,121.7,117.4,89.0,88.4,76.6;HRMS(ESI):Exact masscalcd for C33H22O[M+H]+:435.1743,Found:435.1745。
实施例12:2-(2-萘)-4-苯基-2-(苯乙炔基)-2H-色烯的合成
在空气氛围下,向10.0mL的玻璃瓶中加入2-(2-萘)-4-苯基-2H-色烯半缩酮(105.1mg,0.3mmol),无水氯化铜(4.0mg,0.03mmol),干燥的1,4-二氧六环3mL,苯乙炔(76.6mg,0.75mmol),加热至90℃,搅拌反应,TLC追踪反应情况,待原料消失完全后停止反应。冷却至室温,减压蒸馏除去溶剂,柱层析分离提纯产物,淋洗剂为石油醚,得到无色固体,即为产物2-(2-萘)-4-苯基-2-(苯乙炔基)-2H-色烯,产率为52%,熔点:46-48℃;1HNMR(600MHz,CDCl3):δ=8.32(d,J=1.2Hz,1H),8.00-7.98(m,1H),7.92-7.91(m,2H),7.87-7.85(m,1H),7.52-7.504(m,3H),7.496-7.48(m,3H),7.46-7.44(m,2H),7.42-7.40(m,1H),7.34-7.30(m,3H),7.26-7.23(m,1H),7.16-7.14(m,1H),7.09-7.07(m,1H),6.93(td,J=7.8Hz,1.2Hz,1H),6.04(s,1H);13C{1H}NMR(150MHz,CDCl3):δ=152.5,139.1,137.6,136.0,133.2,132.9,131.9,129.8,128.9,128.7,128.5,128.4,128.2,128.1,127.6,126.5,126.3,126.0,125.6,124.7,124.5,122.3,121.8,121.6,117.2,88.3,88.1,76.2;HRMS(ESI):Exact mass calcd for C33H22O[M+H]+:435.1743,Found:435.1747。
实施例13:4-(对氯苯基)-2-苯基-2-(苯乙炔基)-2H-色烯的合成
在空气氛围下,向10.0mL的玻璃瓶中加入4-(对氯苯基)-2-苯基-2H-色烯半缩酮(100.4mg,0.3mmol),无水氯化铜(4.0mg,0.03mmol),干燥的1,4-二氧六环3mL,苯乙炔(76.6mg,0.75mmol),加热至90℃,搅拌反应,TLC追踪反应情况,待原料消失完全后停止反应。冷却至室温,减压蒸馏除去溶剂,柱层析分离提纯产物,淋洗剂为石油醚,得到无色固体,即为产物4-(对氯苯基)-2-苯基-2-(苯乙炔基)-2H-色烯,产率为57%,熔点:105-107℃;1H NMR(600MHz,CDCl3):δ=7.86-7.85(m,2H),7.44-7.42(m,4H),7.40-7.37(m,5H),7.32-7.29(m,3H),7.24-7.23(m,1H),7.07-7.04(m,2H),6.94-6.91(m,1H),5.91(s,1H);13C{1H}NMR(150MHz,CDCl3):δ=152.4,141.7,136.0,134.7,134.0,131.9,130.2,130.0,128.7,128.63,128.61,128.5,128.2,126.6,125.6,125.2,122.2,121.6,121.4,117.3,88.2,87.8,76.0;HRMS(ESI):Exact mass calcd for C29H19ClO[M+H]+:419.1197,Found:419.1196。
实施例14:4-(2-萘)-2-苯基-2-(苯乙炔基)-2H-色烯的合成
在空气氛围下,向10.0mL的玻璃瓶中加入4-(2-萘)-2-苯基-2H-色烯半缩酮(105.1mg,0.3mmol),无水氯化铜(4.0mg,0.03mmol),干燥的1,4-二氧六环3mL,苯乙炔(76.6mg,0.75mmol),加热至90℃,搅拌反应,TLC追踪反应情况,待原料消失完全后停止反应。冷却至室温,减压蒸馏除去溶剂,柱层析分离提纯产物,淋洗剂为石油醚,得到黄色固体,即为产物4-(2-萘)-2-苯基-2-(苯乙炔基)-2H-色烯,产率为74%,熔点:51-53℃;1HNMR(600MHz,CDCl3):δ=7.95(d,J=1.8Hz,1H),7.92-7.88(m,5H),7.56-7.55(m,1H),7.53-7.50(m,2H),7.47-7.44(m,4H),7.39-7.36(m,1H),7.32-7.29(m,3H),7.26-7.23(m,1H),7.16-7.14(m,1H),7.08-7.06(m,1H),6.94-6.91(m,1H),6.045-6.036(m,1H);13C{1H}NMR(150MHz,CDCl3):δ=152.5,141.9,135.7,135.1,133.3,133.0,131.9,129.8,128.7,128.6,128.5,128.2,128.0,127.9,127.8,127.7,126.8,126.6,126.3,126.2,126.1,125.3,122.3,121.9,121.6,117.2,88.2,88.0,76.2;HRMS(ESI):Exactmass calcd forC33H22O[M+H]+:435.1743,Found:435.1744。
实施例15:6-甲基-2,4-二苯基-2-(苯乙炔基)-2H-色烯的合成
在空气氛围下,向10.0mL的玻璃瓶中加入6-甲基-2,4-二苯基-2H-色烯半缩酮(94.3mg,0.3mmol),无水氯化铜(4.0mg,0.03mmol),干燥的1,4-二氧六环3mL,苯乙炔(76.6mg,0.75mmol),加热至90℃,搅拌反应,TLC追踪反应情况,待原料消失完全后停止反应。冷却至室温,减压蒸馏除去溶剂,柱层析分离提纯产物,淋洗剂为石油醚,得到无色固体,即为产物6-甲基-2,4-二苯基-2-(苯乙炔基)-2H-色烯,产率为67%,熔点:34-35℃;1HNMR(600MHz,CDCl3):δ=7.88-7.86(m,2H),7.46-7.44(m,7H),7.42-7.41(m,2H),7.37-7.36(m,1H),7.32-7.29(m,3H),7.03(dd,J=7.8Hz,1.8Hz,1H),6.95-6.93(m,1H),6.91(d,J=1.8Hz,1H),5.92(s,1H),2.22(s,3H);13C{1H}NMR(150MHz,CDCl3):δ=150.2,142.0,137.7,135.8,131.9,130.7,130.2,128.8,128.6,128.5,128.42,128.39,128.2,128.0,126.6,126.3,125.0,122.3,121.5,116.9,88.2,87.9,75.9;HRMS(ESI):Exact mass calcdfor C30H22O[M+H]+:399.1743,Found:399.1744。
实施例16:7-氯-2,4-二苯基-2-(苯乙炔基)-2H-色烯的合成
在空气氛围下,向10.0mL的玻璃瓶中加入7-氯-2,4-二苯基-2H-色烯半缩酮(100.4mg,0.3mmol),无水氯化铜(4.0mg,0.03mmol),干燥的1,4-二氧六环3mL,苯乙炔(76.6mg,0.75mmol),加热至90℃,搅拌反应,TLC追踪反应情况,待原料消失完全后停止反应。冷却至室温,减压蒸馏除去溶剂,柱层析分离提纯产物,淋洗剂为石油醚,得到无色黏稠液体,即为产物7-氯-2,4-二苯基-2-(苯乙炔基)-2H-色烯,产率为64%,熔点:40-42℃;1HNMR(600MHz,CDCl3):δ=7.86-7.85(m,2H),7.47-7.43(m,9H),7.42-7.39(m,2H),7.33-7.31(m,2H),7.06-7.04(m,2H),6.90-6.89(m,1H),5.93(s,1H);13C{1H}NMR(150MHz,CDCl3):δ=153.1,141.4,137.1,135.0,134.7,131.9,128.8,128.7,128.5,128.3,128.2,126.8,126.6,124.8,122.0,121.7,120.4,117.5,88.5,87.5,76.6;HRMS(ESI):Exactmasscalcd for C29H19ClO[M+H]+:419.1197,Found:419.1198。
实施例17:6-(叔丁基)-4-苯基-2-(苯乙炔基)-2-甲酸甲酯-2H-色烯的合成
在空气氛围下,向10.0mL的玻璃瓶中加入6-(叔丁基)-4-苯基-2-甲酸甲酯-2H-色烯半缩酮(101.4mg,0.3mmol),无水氯化铜(4.0mg,0.03mmol),干燥的1,4-二氧六环3mL,苯乙炔(76.6mg,0.75mmol),加热至90℃,搅拌反应,TLC追踪反应情况,待原料消失完全后停止反应。冷却至室温,减压蒸馏除去溶剂,柱层析分离提纯产物,淋洗剂为石油醚和乙酸乙酯,体积比为250:1,得到橙色黏稠液体,即为产物6-(叔丁基)-4-苯基-2-(苯乙炔基)-2-甲酸甲酯-2H-色烯,产率为76%;1H NMR(600MHz,CDCl3):δ=7.45-7.42(m,7H),7.33-7.27(m,4H),7.104-7.099(m,1H),7.08(d,J=8.4Hz,1H),6.02(s,1H),3.90(s,3H),1.21(s,9H);13C{1H}NMR(150MHz,CDCl3):δ=168.6,149.8,144.6,137.7,137.2,132.1,129.0,128.8,128.4,128.3,128.2,127.0,123.2,121.6,120.3,119.6,116.4,86.4,85.1,74.2,53.6,34.3,31.4;HRMS(ESI):Exact mass calcd for C29H26O3[M+H]+:423.1955,Found:423.1960。
实施例18:6-(叔丁基)-4-(对甲苯基)-2-(苯乙炔基)-2-甲酸甲酯-2H-色烯的合成
在空气氛围下,向10.0mL的玻璃瓶中加入6-(叔丁基)-4-(对甲苯基)-2-甲酸甲酯-2H-色烯半缩酮(105.7mg,0.3mmol),无水氯化铜(4.0mg,0.03mmol),干燥的1,4-二氧六环3mL,苯乙炔(76.6mg,0.75mmol),加热至90℃,搅拌反应,TLC追踪反应情况,待原料消失完全后停止反应。冷却至室温,减压蒸馏除去溶剂,柱层析分离提纯产物,淋洗剂为石油醚和乙酸乙酯,体积比为200:1,得到橙色固体,即为产物6-(叔丁基)-4-(对甲苯基)-2-(苯乙炔基)-2-甲酸甲酯-2H-色烯,产率为76%,熔点:49-51℃;1H NMR(600MHz,CDCl3):δ=7.45-7.44(m,2H),7.33-7.26(m,6H),7.25-7.24(m,2H),7.13(d,J=2.4Hz,1H),7.07(d,J=8.4Hz,1H),5.99(s,1H),3.89(s,3H),2.42(s,3H),1.22(s,9H);13C{1H}NMR(150MHz,CDCl3):δ=168.6,149.8,144.6,138.2,127.6,134.2,132.1,129.1,129.0,128.6,128.2,126.9,123.2,121.6,120.4,119.2,116.4,86.3,85.1,74.1,53.6,34.3,31.4,21.3;HRMS(ESI):Exact mass calcd for C30H28O2[M+H]+:437.2111,Found:453.2060。
实施例19:6-(叔丁基)-4-(间溴苯基)-2-(苯乙炔基)-2-甲酸甲酯-2H-色烯的合成
在空气氛围下,向10.0mL的玻璃瓶中加入6-(叔丁基)-4-(间溴苯基)-2-甲酸甲酯-2H-色烯半缩酮(125.2mg,0.3mmol),无水氯化铜(4.0mg,0.03mmol),干燥的1,4-二氧六环3mL,苯乙炔(76.6mg,0.75mmol),加热至90℃,搅拌反应,TLC追踪反应情况,待原料消失完全后停止反应。冷却至室温,减压除去溶剂,柱层析分离提纯产物,淋洗剂为石油醚和乙酸乙酯,体积比为200:1,得到黄色固体,即为产物6-(叔丁基)-4-(间溴苯基)-2-(苯乙炔基)-2-甲酸甲酯-2H-色烯,产率为43%,熔点:42-44℃;1H NMR(600MHz,CDCl3):δ=7.61-7.60(m,1H),7.55-7.54(m,1H),7.45-7.44(m,2H),7.34-7.32(m,2H),7.31-7.28(m,4H),7.08(d,J=9.0Hz,1H),7.05(d,J=2.4Hz,1H),6.04(s,1H),3.90(s,3H),1.22(s,9H);13C{1H}NMR(150MHz,CDCl3):δ=168.3,149.7,144.8,139.2,136.5,132.1,131.8,131.4,129.9,129.1,128.2,127.4,127.3,122.9,122.5,121.5,120.3,119.9,116.6,86.6,84.7,74.0,53.8,34.3,31.3;HRMS(ESI):Exact mass calcd for C29H25BrO3[M+H]+:501.1060,Found:501.1063。
实施例20:2-乙炔-2,4-二苯基-2H-色烯的合成
在空气氛围下,向25.0mL的圆底烧瓶中加入2,4-二苯基-2-(三甲基硅乙炔)-2H-色烯(114.2mg,0.3mmol),TBAF(86.3mg,0.33mmol,1.1equivs),干燥的四氢呋喃5mL,在0℃条件下搅拌反应,TLC追踪反应情况,待原料消失完全后停止反应。加入10mL饱和氯化铵溶液,用乙酸乙酯萃取,无水硫酸钠干燥有机相。减压除去溶剂,柱层析分离提纯产物,淋洗剂为石油醚和乙酸乙酯,体积比为40:1,得到无色黏稠液体,即为产物2-乙炔-2,4-二苯基-2H-色烯,产率为79%;1H NMR(400MHz,CDCl3):δ=7.84-7.82(m,2H),7.44-7.37(m,8H),7.25-7.23(m,1H),7.14-7.12(m,1H),7.04(d,J=8.0Hz,1H),6.94(t,J=7.6Hz,1H),5.86(s,1H),2.82(s,1H);13C{1H}NMR(100MHz,CDCl3):δ=152.2,141.3,137.4,136.0,129.8,128.8,128.6,128.5,128.4,128.2,126.5,126.0,124.6,121.8,121.7,117.1,82.7,76.2,75.4,76.2,75.4;HRMS(ESI):Exact mass calcd for C23H16O[M+H]+:309.1274,Found:309.1268。
实施例21:1-苄基-4-(2,4-二苯基-2H-色烯)-1H-1,2,3-三唑的合成
在氮气氛围下,向25.0mL的西林特管中加入2-乙炔-2,4-二苯基-2H-色烯(61.7mg,0.2mmol),CuSO4·5H2O(12.5mg,0.05mmol,0.25equivs),抗坏血酸钠(9.9mg,0.05mmol,0.25equivs),加入4.0mL水、4.0mL叔丁醇,再加入苄基叠氮(53.3mg,0.4mmol,2.0equivs)。在80℃条件下搅拌反应,TLC追踪反应情况,待原料消失完全后停止反应。加入10mL饱和氯化铵溶液,用乙酸乙酯萃取,无水硫酸钠干燥有机相。减压除去溶剂,柱层析分离提纯产物,淋洗剂为石油醚和乙酸乙酯,体积比为5:1,得到无色黏稠液体,即为产物1-苄基-4-(2,4-二苯基-2H-色烯)-1H-1,2,3-三唑,产率为55%;1H NMR(400MHz,CDCl3):δ=7.62-7.60(m,2H),7.48(s,1H),7.43-7.30(m,11H),7.24-7.22(m,2H),7.18-7.14(m,1H),7.04-6.99(m,2H),6.83(t,J=7.6Hz,1H),6.47(s,1H),5.50(AB,J=15.6Hz,1H),5.46(AB,J=16.0Hz,1H);13C{1H}NMR(100MHz,CDCl3):δ=152.5,152.4,143.4,137.7,135.7,134.5,129.6,129.1,128.8,128.7,128.34,128.26,128.03,128.02,127.8,126.2,126.1,126.0,122.3,121.6,121.4,116.9,78.2,54.1,;HRMS(ESI):Exact mass calcd for C30H23N3O[M+H]+:442.1914,Found:442.1916。
Claims (9)
2.根据权利要求1所述的C2位炔基化双取代2H-色烯化合物,其特征在于:R3的取代芳基的取代基选自氢,2-氯、甲氧基,3-氯、氟、甲氧基,4-氟、氯、溴、甲基、甲氧基,1-萘或2-萘中的至少一种;
R4的取代芳基的取代基选自氢、2-氯取代基,3-硝基、甲氧基或4-氟、三氟甲基、氯、溴、甲基、甲氧基中的至少一种。
3.权利要求1或者2所述的C2位炔基化双取代2H-色烯化合物的制备方法,其特征在于,包括下述步骤:将2H-色烯半缩酮与氯化铜溶于有机溶剂中,再加入末端炔烃,反应完毕后减压蒸出溶剂,经柱层析分离提纯,即得。
4.根据权利要求3所述的方法,其特征在于:所述末端炔烃的摩尔量为2H-色烯半缩酮摩尔量的1~3倍,优选为2.5倍。
5.根据权利要求3所述的方法,其特征在于:所述氯化铜的摩尔量为2H-色烯半缩酮摩尔量的0.1~0.2倍,优选为0.1倍。
6.根据权利要求3所述的方法,其特征在于:所述有机溶剂的体积用量为2H-色烯半缩酮摩尔量的10倍。
7.根据权利要求3所述的方法,其特征在于:所述有机溶剂选自1,4-二氧六环、乙酸乙酯、四氢呋喃、乙二醇二甲醚、二氯甲烷、1,2-二氯乙烷、1,1,2-三氯丙烷中的一种,优选1,4-二氧六环。
8.根据权利要求3所述的方法,其特征在于:反应温度为60~120℃,优选90℃。
9.根据权利要求3所述的方法,其特征在于:反应时间为1.5~24小时。
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Title |
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FEI YANG等: "Copper-catalyzed oxidative cross-dehydrogenative coupling of 2H-chromenes and terminal alkynes", 《ORG. BIOMOL. CHEM.》, vol. 16, pages 5144 - 5149 * |
HARATHI D. SRINIVAS等: "Enantioselective Copper-Catalyzed Alkynylation of Benzopyranyl Oxocarbenium Ions", 《THE JOURNAL OF ORGANIC CHEMISTRY》, vol. 80, pages 4003 * |
RAJEEV S. MENON等: "The Au(I)-Catalyzed Intramolecular Hydroarylation of Terminal Alkynes Under Mild Conditions: Application to the Synthesis of 2H-Chromenes, Coumarins, Benzofurans, and Dihydroquinolines", 《J. ORG. CHEM.》, vol. 74, pages 8901 - 8903, XP055082760, DOI: 10.1021/jo902032p * |
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