CN112898256A - 1,2-二氢环戊烷并[b]色烯-3,9-二酮类化合物制备方法 - Google Patents
1,2-二氢环戊烷并[b]色烯-3,9-二酮类化合物制备方法 Download PDFInfo
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Abstract
本发明提供1,2‑二氢环戊烷并[b]色烯‑3,9‑二酮类化合物制备方法,涉及化学技术领域。该1,2‑二氢环戊烷并[b]色烯‑3,9‑二酮类化合物制备方法,以3‑碘代色酮、降冰片烯和环丙烯酮为原料,在钯催化剂条件下,在有机溶剂中进行[2+2+1]串联环化反应,合成了一系列1,2‑二氢环戊烷并[b]色烯‑3,9‑二酮类化合物,该类化合物含有潜在生物活性的色酮骨架,可以为生物活性筛选提供化合物源,在药物化学领域具有重要的应用价值。同时,本发明首次以环丙烯酮为唯一羰基源参与钯催化的羰基化反应中,为钯催化的羰基化反应用于羰基化合物的合成提供了新的方法。
Description
技术领域
本发明涉及化学技术领域,具体为1,2-二氢环戊烷并[b]色烯-3,9-二酮类化合物制备方法。
背景技术
杂环结构引入在药物分子,可以降低其亲油性性,提高其溶解性,从而增强药效。色酮骨架作为一类含氧单元在药物分子中广泛存在。因此,发展成本低廉、简单高效的方法实现色酮骨架化合物的合成对新型药物研发及丰富有机合成方法学具有重要意义。
数十年来,许多合成领域科学家对新型化合物的合成方法进行探索,取得丰硕成果。其中,利用过渡金属钯催化反应实现新型化合物的合成蓬勃发展。
然而,我们注意到当前色酮骨架化合物的构建,多以复杂官能化的色酮或邻羟基苯乙酮衍生物为原料,构建结构相对简单的含色酮骨架化合物,而结构复杂的色酮骨架多环化合物的构建方法鲜有报道。
发明内容
(一)解决的技术问题
针对现有技术的不足,本发明提供了以环丙烯酮为唯一羰基源参与羰基化反应的方法,并提供了1,2-二氢环戊烷并[b]色烯-3,9-二酮类化合物制备方法,解决了结构复杂的色酮骨架多环化合物制备方法的问题。
(二)技术方案
为实现以上目的,本发明通过以下技术方案予以实现:1,2-二氢环戊烷并[b]色烯-3,9-二酮类化合物制备方法,以1,2-二氢环戊烷并[b]色烯-3,9-二酮化合物4a为例,所用原料及制备方法为:
将3-碘代色酮(0.2mmol),二苯基环丙烯酮(42.1mg,0.2mmol),降冰片烯(0.8mmol,75.3mg),碳酸铯(130.4mg,0.4mmol),氯化钯(3.5mg,0.02mmol),P(4-CF3-C6H4)3(18.7mg,0.04mmol),2.0mL氟苯加入到4mL反应瓶中,100℃反应24小时,待反应结束后,冷却至室温,经硅胶柱层析分离纯化(乙酸乙酯/石油醚=40:1~5:1)(分离方法都是柱层析分离)得到黄色固体4a,其产量为48.5mg,产率为91%,熔点为116.7~118.5℃,波谱数据为:1H NMR(400MHz,CDCl3)δ8.07(dd,J=8.0,1.6Hz,1H),7.62(ddd,J=8.8,7.2,1.6Hz,1H),7.44(d,J=8.2Hz,1H),7.35–7.30(m,1H),2.99(d,J=5.4Hz,1H),2.53(d,J=4.0Hz,1H),2.43(d,J=4.0Hz,1H),2.36(d,J=5.2Hz,1H),1.64(tt,J=11.6,4.2Hz,1H),1.53(tt,J=12.0,4.0Hz,1H),1.42–1.34(m,1H),1.29–1.22(m,1H),0.95(d,J=11.0Hz,1H),0.87(d,J=11.0Hz,1H);13CNMR(100MHz,CDCl3)δ202.2,177.6,159.3,155.8,141.1,134.8,125.8,125.6,124.8,119.0,53.0,42.0,39.7,37.2,31.9,28.8,28.4;HRMS(ESI-TOF):calcd.for C17H15O3[M+H]+267.1016;found 267.1012。
(三)有益效果
本发明提供了1,2-二氢环戊烷并[b]色烯-3,9-二酮类化合物制备方法。具备以下有益效果:
本发明以简单易得的3-碘代色酮、降冰片烯和环丙烯酮为原料,通过钯催化“一锅法”构建结构复杂的含色酮骨架多环化合物,同时,本发明首次以环丙烯酮为唯一羰基源参与钯催化的羰基化反应中,为钯催化的羰基化反应用于羰基化合物的合成提供了新的方法。
附图说明
图1为本发明化合物4a的单晶-X射线衍射结构;
图2为本发明化合物4a的核磁共振氢谱图;
图3为本发明化合物4a的核磁共振碳谱图。
具体实施方式
下面将结合本发明实施例中的附图,对本发明实施例中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。
实施例一:
本发明实施例提供1,2-二氢环戊烷并[b]色烯-3,9-二酮类化合物制备方法,以1,2-二氢环戊烷并[b]色烯-3,9-二酮化合物4a为例,所用原料及制备方法为:
将3-碘代色酮(0.2mmol),二苯基环丙烯酮(42.1mg,0.2mmol),降冰片烯(0.8mmol,75.3mg),碳酸铯(130.4mg,0.4mmol),氯化钯(3.5mg,0.02mmol),P(4-CF3-C6H4)3(18.7mg,0.04mmol),2.0mL氟苯加入到4mL反应瓶中,100℃反应24小时,待反应结束后,冷却至室温,经硅胶柱层析分离纯化(乙酸乙酯/石油醚=40:1~5:1)(分离方法都是柱层析分离)得到黄色固体4a,其产量为48.5mg,产率为91%,熔点为116.7~118.5℃,波谱数据为:1H NMR(400MHz,CDCl3)δ8.07(dd,J=8.0,1.6Hz,1H),7.62(ddd,J=8.8,7.2,1.6Hz,1H),7.44(d,J=8.2Hz,1H),7.35–7.30(m,1H),2.99(d,J=5.4Hz,1H),2.53(d,J=4.0Hz,1H),2.43(d,J=4.0Hz,1H),2.36(d,J=5.2Hz,1H),1.64(tt,J=11.6,4.2Hz,1H),1.53(tt,J=12.0,4.0Hz,1H),1.42–1.34(m,1H),1.29–1.22(m,1H),0.95(d,J=11.0Hz,1H),0.87(d,J=11.0Hz,1H);13C NMR(100MHz,CDCl3)δ202.2,177.6,159.3,155.8,141.1,134.8,125.8,125.6,124.8,119.0,53.0,42.0,39.7,37.2,31.9,28.8,28.4;HRMS(ESI-TOF):calcd.for C17H15O3[M+H]+267.1016;found 267.1012。
实施例二:
以制备结构式如下的1,2-二氢环戊烷并[b]色烯-3,9-二酮化合物4b为例,所用原料及制备方法为:
在实施例1中,所用的3-碘代色酮用等摩尔的3-碘-5-甲氧基色酮替换,其他步骤与实施例相同,得到黄色固体4b,其产量为30.3mg,产率为51%,熔点为163.8~165.0℃,波谱数据为:1H NMR(400MHz,CDCl3)δ7.60(t,J=8.4Hz,1H),7.13(d,J=8.4Hz,1H),6.84(d,J=8.4Hz,1H),3.98(s,3H),3.06(d,J=5.2Hz,1H),2.67(d,J=3.8Hz,1H),2.53(d,J=3.4Hz,1H),2.43(d,J=5.2Hz,1H),1.80–1.69(m,1H),1.67–1.58(m,1H),1.52–1.43(m,1H),1.39–1.30(m,1H),1.05(d,J=11.0Hz,1H),0.98(d,J=11.0Hz,1H);13C NMR(100MHz,CDCl3)δ202.6,177.7,160.4,158.3,157.9,142.9,135.2,115.9,111.0,107.0,56.6,53.4,42.3,39.8,37.3,32.1,29.0,28.7;HRMS(ESI-TOF):calcd.for C18H16O4[M+H]+297.1121;found 297.1122。
实施例三
以制备结构式如下的1,2-二氢环戊烷并[b]色烯-3,9-二酮化合物4c为例,所用原料及制备方法为:
在实施例1中,所用的3-碘代色酮用等摩尔的3-碘-5-氟色酮替换,其他步骤与实施例相同,得到黄色固体4c,其产量为35.3mg,产率为62%,熔点为168.7~170.1℃,波谱数据为:1H NMR(400MHz,CDCl3)δ7.66(td,J=8.4,5.6Hz,1H),7.39(d,J=8.6Hz,1H),7.09(dd,J=10.2,8.6Hz,1H),3.09(d,J=5.2Hz,1H),2.66(d,J=4.0Hz,1H),2.56(d,J=3.6Hz,1H),2.46(d,J=5.2Hz,1H),1.76(tt,J=11.8,4.2Hz,1H),1.65(tt,J=12.0,4.2Hz,1H),1.53–1.44(m,1H),1.41–1.32(m,1H),1.08(d,J=11.0Hz,1H),0.98(d,J=11.0Hz,1H);13C NMR(100MHz,CDCl3)δ202.2,176.3,161.1(d,J=266.2Hz),158.7,157.2,142.2,135.1(d,J=10.9Hz),115.7(d,J=10.5Hz),115.1(d,J=4.6Hz),112.8(d,J=20.7Hz),53.36,42.22,39.92,37.39,32.15,29.05,28.67;HRMS(ESI-TOF):calcd.forC17H14FO3[M+H]+285.0921;found 285.0921。
实施例四
以制备结构式如下的1,2-二氢环戊烷并[b]色烯-3,9-二酮化合物4d为例,所用原料及制备方法为:
在实施例1中,所用的3-碘代色酮用等摩尔的3-碘-5-氯色酮替换,其他步骤与实施例相同,得到黄色固体4d,其产量为37.3mg,产率为62%,熔点为175.8~177.1℃,波谱数据为:1H NMR(400MHz,CDCl3)δ7.58(t,J=8.2Hz,1H),7.50(d,J=8.0Hz,1H),7.42(d,J=7.6Hz,1H),3.09(d,J=5.2Hz,1H),2.68(d,J=3.6Hz,1H),2.56(d,J=3.2Hz,1H),2.46(d,J=5.2Hz,1H),1.81–1.71(m,1H),1.70–1.60(m,1H),1.51–1.44(m,1H),1.42–1.33(m,1H),1.08(d,J=11.0Hz,1H),0.99(d,J=11.0Hz,1H);13C NMR(100MHz,CDCl3)δ202.3,176.9,158.2,157.9,142.3,134.2,134.1,128.9,122.2,118.4,53.5,42.4,39.9,37.4,32.2,29.0,28.7;HRMS(ESI-TOF):calcd.for C17H13ClO3[M+H]+301.0626;found 301.0623。
实施例五
以制备结构式如下的1,2-二氢环戊烷并[b]色烯-3,9-二酮化合物4e为例,所用原料及制备方法为:
在实施例1中,所用的3-碘代色酮用等摩尔的3-碘-6-甲基色酮替换,其他步骤与实施例相同,得到黄色固体4e,其产量为44.9mg,产率为80%,熔点为164.8~165.3℃,波谱数据为:1H NMR(400MHz,CDCl3)δ8.00(s,1H),7.53(dd,J=8.6,1.8Hz,1H),7.47(d,J=8.6Hz,1H),3.10(d,J=5.2Hz,1H),2.65(d,J=3.8Hz,1H),2.55(d,J=3.4Hz,1H),2.45(s,4H),1.81–1.70(m,1H),1.69–1.58(m,1H),1.53–1.45(m,1H),1.42–1.32(m,1H),1.06(d,J=11.0Hz,1H),0.97(d,J=11.0Hz,1H);13C NMR(100MHz,CDCl3)δ202.7,178.1,159.4,154.4,141.3,136.4,136.0,125.4,124.8,119.0,53.3,42.3,39.9,37.4,32.1,29.1,28.7,21.0;HRMS(ESI-TOF):calcd.for C18H16O3[M+H]+281.1172;found 281.1173。
实施例六
以制备结构式如下的1,2-二氢环戊烷并[b]色烯-3,9-二酮化合物4f为例,所用原料及制备方法为:
在实施例1中,所用的3-碘代色酮用等摩尔的3-碘-6-甲氧基色酮替换,其他步骤与实施例相同,得到黄色固体4f,其产量为42.1mg,产率为71%,熔点为181.5~182.9℃,波谱数据为:1H NMR(400MHz,CDCl3)δ7.56(d,J=3.0Hz,1H),7.51(d,J=9.2Hz,1H),7.30(dd,J=9.2,3.0Hz,1H),3.89(s,3H),3.11(d,J=5.2Hz,1H),2.65(d,J=3.6Hz,1H),2.56(d,J=3.2Hz,1H),2.46(d,J=5.2Hz,1H),1.80–1.70(m,1H),1.69–1.59(m,1H),1.54–1.45(m,1H),1.41–1.32(m,1H),1.06(d,J=11.0Hz,1H),0.97(d,J=11.0Hz,1H);13C NMR(100MHz,CDCl3)δ202.7,177.8,159.3,157.5,150.9,140.4,125.8,125.2,120.6,105.1,56.1,53.3,42.2,40.0,37.4,32.1,29.1,28.7;HRMS(ESI-TOF):calcd.for C18H16O4[M+H]+297.1121;found 297.1122。
实施例七
以制备结构式如下的1,2-二氢环戊烷并[b]色烯-3,9-二酮化合物4g为例,所用原料及制备方法为:
在实施例1中,所用的3-碘代色酮用等摩尔的3-碘-6-氟色酮替换,其他步骤与实施例相同,得到黄色固体4g,其产量为39.8mg,产率为70%,熔点为160.6~162.1℃,波谱数据为:1H NMR(400MHz,CDCl3)δ7.86(dd,J=8.0,3.2Hz,1H),7.61(dd,J=9.2,4.0Hz,1H),7.46(ddd,J=9.2,7.6,3.2Hz,1H),3.12(d,J=5.4Hz,1H),2.66(d,J=3.8Hz,1H),2.57(d,J=3.4Hz,1H),2.48(d,J=5.2Hz,1H),1.75(dq,J=11.6,3.8Hz,1H),1.66(tt,J=12.0,4.0Hz,1H),1.54–1.46(m,1H),1.42–1.33(m,1H),1.08(d,J=11.0Hz,1H),0.98(d,J=11.0Hz,1H);13C NMR(100MHz,CDCl3)δ202.4,177.3,159.9(d,J=248.4Hz),159.8,152.3,140.5,126.3(d,J=7.3Hz),123.3(d,J=25.5Hz),121.4(d,J=8.1Hz),111.1(d,J=23.8Hz),53.4,42.2,40.0,37.5,32.2,29.1,28.7;HRMS(ESI-TOF):calcd.for C17H14FO3[M+H]+285.0921;found 285.0922。
实施例八
以制备结构式如下的1,2-二氢环戊烷并[b]色烯-3,9-二酮化合物4h为例,所用原料及制备方法为:
在实施例1中,所用的3-碘代色酮用等摩尔的3-碘-6-氯色酮替换,其他步骤与实施例相同,得到黄色固体4h,其产量为45.2mg,产率为75%,熔点为196.8~198.7℃,波谱数据为:1H NMR(400MHz,CDCl3)δ8.17(d,J=2.4Hz,1H),7.66(dd,J=9.0,2.4Hz,1H),7.55(d,J=9.0Hz,1H),3.11(d,J=5.2Hz,1H),2.65(d,J=3.4Hz,1H),2.57(d,J=3.2Hz,1H),2.48(d,J=5.2Hz,1H),1.76(tt,J=11.6,4.2Hz,1H),1.70–1.60(m,1H),1.53–1.43(m,1H),1.41–1.33(m,1H),1.08(d,J=11.0Hz,1H),0.97(d,J=11.0Hz,1H);13C NMR(100MHz,CDCl3)δ202.2,176.8,159.7,154.5,141.2,135.3,132.0,126.0,125.6,121.0,53.3,42.2,40.0,37.5,32.2,29.1,28.7;HRMS(ESI-TOF):calcd.for C17H13ClO3[M+H]+301.0626;found301.0627。
实施例九
以制备结构式如下的1,2-二氢环戊烷并[b]色烯-3,9-二酮化合物4i为例,所用原料及制备方法为:
在实施例1中,所用的3-碘代色酮用等摩尔的3-碘-6-溴色酮替换,其他步骤与实施例相同,得到黄色固体4i,其产量为39.4mg,产率为57%,熔点为185.3~187.1℃,波谱数据为:1H NMR(400MHz,CDCl3)δ8.36(d,J=2.4Hz,1H),7.81(dd,J=9.0,2.4Hz,1H),7.50(d,J=9.0Hz,1H),3.12(d,J=5.2Hz,1H),2.66(d,J=3.6Hz,1H),2.58(d,J=3.4Hz,1H),2.49(d,J=5.2Hz,1H),1.83–1.72(m,1H),1.71–1.61(m,1H),1.55–1.46(m,1H),1.43–1.34(m,1H),1.09(d,J=11.0Hz,1H),0.98(d,J=11.0Hz,1H);13C NMR(100MHz,CDCl3)δ202.3,176.7,159.7,155.0,141.4,138.1,128.8,126.4,121.2,119.5,53.4,42.3,40.0,37.5,32.2,29.1,28.7;HRMS(ESI-TOF):calcd.for C17H13BrO3[M+H]+345.0121;found 345.0121。
实施例十
以制备结构式如下的1,2-二氢环戊烷并[b]色烯-3,9-二酮化合物4j为例,所用原料及制备方法为:
在实施例1中,所用的3-碘代色酮用等摩尔的3-碘-6-氰基色酮替换,其他步骤与实施例相同,得到黄色固体4j,其产量为41.4mg,产率为71%,熔点为199.7~200.9℃,波谱数据为:1H NMR(400MHz,CDCl3)δ8.59(d,JJ=2.0Hz,1H),7.97(dd,JJ=8.8,2.0Hz,1H),7.73(d,JJ=8.8Hz,1H),3.15(d,J=5.3Hz,1H),2.67(d,J=3.9Hz,1H),2.61(d,J=3.6Hz,1H),2.52(d,J=5.3Hz,1H),1.79(tt,J=11.7,4.2Hz,1H),1.74–1.63(m,1H),1.56–1.48(m,1H),1.44–1.36(m,1H),1.13(d,J=11.1Hz,1H),1.00(d,J=11.1Hz,1H);13C NMR(100MHz,CDCl3)δ200.7,175.3,159.0,157.0,141.0,136.2,130.9,124.5,120.0,116.3,109.3,52.4,41.3,39.1,36.5,31.3,28.1,27.7;HRMS(ESI-TOF):calcd.for C18H13NO3[M+H]+292.0968;found 292.0967。
实施例十一
以制备结构式如下的1,2-二氢环戊烷并[b]色烯-3,9-二酮化合物4k为例,所用原料及制备方法为:
在实施例1中,所用的3-碘代色酮用等摩尔的3-碘-6-硝基色酮替换,其他步骤与实施例相同,得到黄色固体4k,其产量为54.2mg,产率为87%,熔点为214.9~216.1℃,波谱数据为:1H NMR(400MHz,CDCl3)δ9.10(d,J=2.8Hz,1H),8.57(dd,J=9.2,2.8Hz,1H),7.77(d,J=9.2Hz,1H),3.16(d,J=5.2Hz,1H),2.68(d,J=3.6Hz,1H),2.61(d,J=3.0Hz,1H),2.53(d,J=5.2Hz,1H),1.85–1.75(m,1H),1.73–1.63(m,1H),1.56–1.48(m,1H),1.44–1.35(m,1H),1.13(dd,J=11.0,1.2Hz,1H),1.00(dd,J=11.0,1.2Hz,1H);13C NMR(100MHz,CDCl3)δ201.7,176.5,160.0,159.0,145.2,141.7,129.3,125.2,123.0,121.1,53.4,42.2,40.1,37.5,32.3,29.1,28.6;HRMS(ESI-TOF):calcd.for C17H13NO5[M+H]+312.0866;found312.0866。
实施例十二
以制备结构式如下的1,2-二氢环戊烷并[b]色烯-3,9-二酮化合物4l为例,所用原料及制备方法为:
在实施例1中,所用的3-碘代色酮用等摩尔的3-碘-7-甲基色酮替换,其他步骤与实施例相同,得到黄色固体4l,其产量为39.3mg,产率为70%,熔点为141.0~142.5℃,波谱数据为:1H NMR(400MHz,CDCl3)δ8.08(d,J=8.2Hz,1H),7.34(s,1H),7.23(d,J=8.4Hz,1H),3.08(d,J=5.2Hz,1H),2.63(d,J=3.4Hz,1H),2.53(d,J=3.4Hz,1H),2.47(s,3H),2.43(d,J=5.2Hz,1H),1.78–1.68(m,1H),1.67–1.57(m,1H),1.50–1.43(m,1H),1.38–1.30(m,1H),1.04(d,J=11.0Hz,1H),0.96(d,J=11.0Hz,1H);13C NMR(100MHz,CDCl3)δ202.7,177.8,159.4,156.3,146.8,141.6,127.4,125.9,122.9,118.9,53.3,42.2,39.9,37.4,32.1,29.1,28.7,22.7;HRMS(ESI-TOF):calcd.for C18H16O3[M+H]+281.1172;found281.1171。
实施例十三
以制备结构式如下的1,2-二氢环戊烷并[b]色烯-3,9-二酮化合物4m为例,所用原料及制备方法为:
在实施例1中,所用的3-碘代色酮用等摩尔的3-碘-7-甲氧基色酮替换,其他步骤与实施例相同,得到黄色固体4m,其产量为42.7mg,产率为72%,熔点为179.6~180.9℃,波谱数据为:1H NMR(400MHz,CDCl3)δ8.13(d,J=9.0Hz,1H),7.02–6.92(m,2H),3.89(s,3H),3.09(d,J=5.2Hz,1H),2.65(d,J=3.8Hz,1H),2.55(d,J=3.4Hz,1H),2.45(d,J=5.2Hz,1H),1.82–1.70(m,1H),1.69–1.59(m,1H),1.53–1.45(m,1H),1.40–1.32(m,1H),1.06(d,J=11.0Hz,1H),0.98(d,J=11.0Hz,1H);13C NMR(100MHz,CDCl3)δ202.5,177.1,165.2,159.4,158.2,142.0,127.5,119.1,115.5,101.0,56.1,53.4,42.3,39.9,37.4,32.1,29.1,28.7;HRMS(ESI-TOF):calcd.for C18H16O4[M+H]+297.1121;found 297.1122。
实施例十四
以制备结构式如下的1,2-二氢环戊烷并[b]色烯-3,9-二酮化合物4n为例,所用原料及制备方法为:
在实施例1中,所用的3-碘代色酮用等摩尔的3-碘-7-氟色酮替换,其他步骤与实施例相同,得到黄色固体4n,其产量为46.1mg,产率为81%,熔点为192.6~194.0℃,波谱数据为:1H NMR(400MHz,CDCl3)δ8.26(dd,J=8.8,6.4Hz,1H),7.26(dd,J=8.8,2.0Hz,1H),7.21–7.14(m,1H),3.11(d,J=5.2Hz,1H),2.65(d,J=3.4Hz,1H),2.57(d,J=2.8Hz,1H),2.48(d,J=5.2Hz,1H),1.81–1.72(m,1H),1.70–1.61(m,1H),1.53–1.46(m,1H),1.41–1.33(m,1H),1.08(d,J=11.0Hz,1H),0.99(d,J=11.0Hz,1H);13C NMR(100MHz,CDCl3)δ202.1,177.0,166.4(d,J=257.3Hz),160.0,157.4(d,J=13.4Hz),128.8(d,J=10.8Hz),122.0(d,J=2.3Hz),114.8(d,J=22.9Hz),105.9(d,J=25.6Hz);53.4,42.2,40.0,37.5,32.1,29.1,28.7;HRMS(ESI-TOF):calcd.for C17H13FO3[M+H]+285.0921;found 285.0924。
实施例十五
以制备结构式如下的1,2-二氢环戊烷并[b]色烯-3,9-二酮化合物4o为例,所用原料及制备方法为:
在实施例1中,所用的3-碘代色酮用等摩尔的3-碘-7-氯色酮替换,其他步骤与实施例相同,得到黄色固体4o,其产量为44.0mg,产率为73%,熔点为193.8~195.2℃,波谱数据为:1H NMR(400MHz,CDCl3)δ8.13(d,J=8.6Hz,1H),7.55(d,J=1.6Hz,1H),7.38(dd,J=8.6,1.6Hz,1H),3.08(d,J=5.2Hz,1H),2.62(d,J=3.6Hz,1H),2.54(d,J=3.2Hz,1H),2.45(d,J=5.2Hz,1H),1.74(tt,J=11.6,4.0Hz,1H),1.67–1.58(m,1H),1.51–1.43(m,1H),1.38–1.31(m,1H),1.06(d,J=11.0Hz,1H),0.96(d,J=11.0Hz,1H);13C NMR(100MHz,CDCl3)δ202.0,177.1,159.6,156.2,141.7,141.1,127.5,126.7,123.6,119.1,53.3,42.2,40.0,37.4,32.1,29.0,28.6;HRMS(ESI-TOF):calcd.for C17H13ClO3[M+H]+301.0626;found301.0626。
实施例十六
以制备结构式如下的1,2-二氢环戊烷并[b]色烯-3,9-二酮化合物4p为例,所用原料及制备方法为:
在实施例1中,所用的3-碘代色酮用等摩尔的3-碘-7-溴色酮替换,其他步骤与实施例相同,得到黄色固体4p,其产量为37.3mg,产率为54%,熔点为196.5~197.8℃,波谱数据为:1H NMR(400MHz,CDCl3)δ8.11(d,J=8.6Hz,1H),7.79(d,J=1.4Hz,1H),7.57(dd,J=8.6,1.4Hz,1H),3.12(d,J=5.4Hz,1H),2.66(d,J=3.6Hz,1H),2.58(d,J=3.4Hz,1H),2.48(d,J=5.4Hz,1H),1.83–1.72(m,1H),1.70–1.62(m,1H),1.54–1.47(m,1H),1.42–1.35(m,1H),1.09(d,J=11.0Hz,1H),0.99(d,J=11.0Hz,1H);13C NMR(100MHz,CDCl3)δ202.1,177.3,159.6,156.2,141.8,129.7,129.5,127.6,124.0,122.3,53.4,42.3,40.0,37.5,32.2,29.2,28;HRMS(ESI-TOF):calcd.for C17H13BrO3[M+H]+345.0121;found 345.0121。
实施例十七
以制备结构式如下的1,2-二氢环戊烷并[b]色烯-3,9-二酮化合物4q为例,所用原料及制备方法为:
在实施例1中,所用的3-碘代色酮用等摩尔的3-碘-8-甲基色酮替换,其他步骤与实施例相同,得到黄色固体4q,其产量为39.9mg,产率为71%,熔点为141.8~143.2℃,波谱数据为:1H NMR(400MHz,CDCl3)δ8.09(dd,J=8.0,1.0Hz,1H),7.57(d,J=6.8Hz,1H),7.34(t,J=7.6Hz,1H),3.12(d,J=5.2Hz,1H),2.67(d,J=4.0Hz,1H),2.57(d,J=3.8Hz,1H),2.54(s,3H),2.47(d,J=5.2Hz,1H),1.83–1.72(m,1H),1.66(tt,J=12.0,4.0Hz,1H),1.57–1.46(m,1H),1.43–1.33(m,1H),1.07(d,J=11.0Hz,1H),1.00(d,J=11.0Hz,1H);13CNMR(100MHz,CDCl3)δ202.6,178.4,159.5,154.6,141.2,136.1,129.0,125.4,125.1,123.8,53.3,42.2,40.0,37.5,32.1,29.1,28.7,15.9;HRMS(ESI-TOF):calcd.for C18H16O3[M+H]+281.1172;found281.1171。
实施例十八
以制备结构式如下的1,2-二氢环戊烷并[b]色烯-3,9-二酮化合物4r为例,所用原料及制备方法为:
在实施例1中,所用的3-碘代色酮用等摩尔的3-碘-8-氯色酮替换,其他步骤与实施例相同,得到黄色固体4r,其产量为49.4mg,产率为82%,熔点为148.5~150.2℃,波谱数据为:1H NMR(400MHz,CDCl3)δ8.08(dd,J=8.0,1.2Hz,1H),7.75(dd,J=7.8,1.2Hz,1H),7.35(t,J=8.0Hz,1H),3.09(d,J=5.2Hz,1H),2.62(d,J=3.6Hz,1H),2.55(d,J=3.2Hz,1H),2.47(d,J=5.2Hz,1H),1.74(ddd,J=12.0,8.0,4.2Hz,1H),1.63(ddd,J=12.0,8.0,4.2Hz,1H),1.51–1.43(m,1H),1.39–1.32(m,1H),1.06(d,J=11.0Hz,1H),0.97(d,J=11.0Hz,1H);13C NMR(100MHz,CDCl3)δ201.5,177.3,159.5,151.8,141.2,135.3,126.3,125.8,124.7,124.4,53.2,42.1,40.0,37.4,32.1,29.0,28.6;HRMS(ESI-TOF):calcd.forC17H13ClO3[M+H]+301.0626;found301.0626。
实施例十九
以制备结构式如下的1,2-二氢环戊烷并[b]色烯-3,9-二酮化合物4s为例,所用原料及制备方法为:
在实施例1中,所用的3-碘代色酮用等摩尔的3-碘-6,7-二甲基色酮替换,其他步骤与实施例相同,得到黄色固体4s,其产量为38.9mg,产率为66%,熔点为178.6~179.5℃,波谱数据为:1H NMR(400MHz,CDCl3)δ7.94(s,1H),7.33(s,1H),3.10(d,J=5.2Hz,1H),2.65(d,JJ=3.6Hz,1H),2.55(d,J=3.2Hz,1H),2.44(d,J=5.2Hz,1H),2.38(s,3H),2.35(s,3H),1.80–1.70(m,1H),1.69–1.59(m,1H),1.53–1.44(m,1H),1.40–1.32(m,1H),1.05(d,J=11.0Hz,1H),0.97(d,J=11.0Hz,1H);13C NMR(100MHz,CDCl3)δ202.8,177.9,159.3,154.7,145.9,141.4,135.4,125.7,123.0,119.2,53.3,42.3,39.9,37.4,32.1,29.1,28.7,20.7,19.5;HRMS(ESI-TOF):calcd.for C19H18O3[M+H]+295.1329;found 295.1328。
实施例二十
以制备结构式如下的1,2-二氢环戊烷并[b]色烯-3,9-二酮化合物4t为例,所用原料及制备方法为:
在实施例1中,所用的3-碘代色酮用等摩尔的3-碘-6,8-二甲基色酮替换,其他步骤与实施例相同,得到黄色固体4t,其产量为41.2mg,产率为70%,熔点为166.3~169.9℃,波谱数据为:1H NMR(400MHz,CDCl3)δ7.85(s,1H),7.39(s,1H),3.11(d,J=5.2Hz,1H),2.66(d,J=3.8Hz,1H),2.56(d,J=3.2Hz,1H),2.49(s,3H),2.46(d,J=5.2Hz,1H),2.41(s,3H),1.81–1.70(m,1H),1.69–1.60(m,1H),1.53–1.46(m,1H),1.40–1.33(dd,J=m,1H),1.06(d,J=11.0Hz,1H),0.98(d,J=11.0Hz,1H);13C NMR(100MHz,CDCl3)δ202.7,178.4,159.3,152.9,141.0,137.4,135.4,128.6,124.8,123.0,53.3,42.2,40.0,37.5,32.1,29.1,28.7,21.0,15.8;HRMS(ESI-TOF):calcd.for C19H18O3[M+H]+295.1329;found295.1328。
实施例二十一
以制备结构式如下的1,2-二氢环戊烷并[b]色烯-3,9-二酮化合物4u为例,所用原料及制备方法为:
在实施例1中,所用的3-碘代色酮用等摩尔的3-碘-6-氯-7-甲基色酮替换,其他步骤与实施例相同,得到黄色固体4u,其产量为41.0mg,产率为65%,熔点为180.2~181.7℃,波谱数据为:1H NMR(400MHz,CDCl3)δ8.17(s,1H),7.46(s,1H),3.10(d,J=5.2Hz,1H),2.69–2.62(m,1H),2.58–2.54(m,1H),2.53–2.44(m,4H),1.83–1.60(m,3H),1.54–1.45(m,1H),1.42–1.33(m,1H),1.08(d,J=10.8Hz,1H),0.97(d,J=10.8Hz,1H);13C NMR(100MHz,CDCl3)δ202.3,176.8,159.6,154.4,144.7,141.3,132.8,125.8,124.2,120.9,53.3,42.2,40.0,37.5,32.2,29.1,28.7,21.1;HRMS(ESI-TOF):calcd.for C18H15ClO3[M+H]+315.0782;found 315.0780。
实施例二十二
以制备结构式如下的1,2-二氢环戊烷并[b]色烯-3,9-二酮化合物4v为例,所用原料及制备方法为:
在实施例1中,所用的3-碘代色酮用等摩尔的3-碘-4H-苯并[h]色烯-4-酮替换,其他步骤与实施例相同,得到黄色固体4u,其产量为35.5mg,产率为56%,熔点为165.9~167.7℃,波谱数据为:1H NMR(400MHz,CDCl3)δ8.63(d,J=8.2Hz,1H),8.15(d,J=8.8Hz,1H),7.92(d,J=7.8Hz,1H),7.79(d,J=8.8Hz,1H),7.75–7.65(m,2H),3.18(d,J=5.2Hz,1H),2.73(d,J=3.2Hz,1H),2.62(d,J=2.8Hz,1H),2.53(d,J=5.2Hz,1H),1.84–1.75(m,1H),1.72–1.65(m,1H),1.58–1.50(m,1H),1.47–1.36(m,1H),1.10(d,J=11.0Hz,1H),1.04(d,J=11.0Hz,1H);13C NMR(100MHz,CDCl3)δ202.1,177.7,159.1,153.8,142.9,136.5,130.1,128.2,127.6,126.2,124.4,123.1,121.7,120.7,53.5,42.4,40.0,37.5,32.2,29.2,28.8;HRMS(ESI-TOF):calcd.for C21H16O3[M+H]+317.1172;found 317.1171。
实施例二十三
以制备结构式如下的1,2-二氢环戊烷并[b]色烯-3,9-二酮化合物4w为例,所用原料及制备方法为:
在实施例1中,所用的3-碘代色酮用等摩尔的2-碘-1H-苯并[f]色烯-1-酮替换,其他步骤与实施例相同,得到黄色固体4w,其产量为31.7mg,产率为50%,熔点为202.4~203.8℃,波谱数据为:1H NMR(400MHz,CDCl3)δ10.03(d,J=8.6Hz,1H),8.14(d,J=9.2Hz,1H),7.92(d,J=8.0Hz,1H),7.82–7.76(m,1H),7.68–7.60(m,2H),3.19(d,JJ=5.2Hz,1H),2.76(d,JJ=3.8Hz,1H),2.60(d,J=3.6Hz,1H),2.51(d,J=5.2Hz,1H),1.80(tt,J=11.8,4.2Hz,1H),1.68(tt,J=11.8,4.2Hz,1H),1.61–1.50(m,1H),1.47–1.36(m,1H),1.10(d,J=11.0Hz,1H),1.03(d,JJ=11.0Hz,1H);13C NMR(100MHz,CDCl3)δ202.3,179.7,157.8,157.6,144.2,137.1,130.7,130.6,129.9,128.6,127.3,126.9,118.8,118.2,53.7,42.6,39.9,37.5,32.3,29.2,28.8;HRMS(ESI-TOF):calcd.for C21H16O3[M+H]+317.1172;found317.1168
尽管已经示出和描述了本发明的实施例,对于本领域的普通技术人员而言,可以理解在不脱离本发明的原理和精神的情况下可以对这些实施例进行多种变化、修改、替换和变型,本发明的范围由所附权利要求及其等同物限定。
Claims (1)
1.1,2-二氢环戊烷并[b]色烯-3,9-二酮类化合物制备方法,其特征在于:以1,2-二氢环戊烷并[b]色烯-3,9-二酮化合物4a为例,所用原料及制备方法为:
将3-碘代色酮(0.2mmol),二苯基环丙烯酮(42.1mg,0.2mmol),降冰片烯(0.8mmol,75.3mg),碳酸铯(130.4mg,0.4mmol),氯化钯(3.5mg,0.02mmol),P(4-CF3-C6H4)3(18.7mg,0.04mmol),2.0mL氟苯加入到4mL反应瓶中,100℃反应24小时,待反应结束后,冷却至室温,经硅胶柱层析分离纯化(乙酸乙酯/石油醚=40:1~5:1)(分离方法都是柱层析分离)得到黄色固体4a,其产量为48.5mg,产率为91%,熔点为116.7~118.5℃,波谱数据为:1H NMR(400MHz,CDCl3)δ8.07(dd,J=8.0,1.6Hz,1H),7.62(ddd,J=8.8,7.2,1.6Hz,1H),7.44(d,J=8.2Hz,1H),7.35–7.30(m,1H),2.99(d,J=5.4Hz,1H),2.53(d,J=4.0Hz,1H),2.43(d,J=4.0Hz,1H),2.36(d,J=5.2Hz,1H),1.64(tt,J=11.6,4.2Hz,1H),1.53(tt,J=12.0,4.0Hz,1H),1.42–1.34(m,1H),1.29–1.22(m,1H),0.95(d,J=11.0Hz,1H),0.87(d,J=11.0Hz,1H);13C NMR(100MHz,CDCl3)δ202.2,177.6,159.3,155.8,141.1,134.8,125.8,125.6,124.8,119.0,53.0,42.0,39.7,37.2,31.9,28.8,28.4;HRMS(ESI-TOF):calcd.forC17H15O3[M+H]+267.1016;found 267.1012。
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3265743A (en) * | 1962-05-14 | 1966-08-09 | Ethyl Corp | Production of dihalocarbene adducts |
CA2079373A1 (en) * | 1991-09-30 | 1993-03-31 | Petpiboon Prasit | (azaarylmethoxy)indoles as inhibitors of leukotriene biosynthesis |
AU2010205799A1 (en) * | 2009-01-15 | 2011-07-28 | Syngenta Limited | Novel herbicides |
CN111732567A (zh) * | 2020-06-17 | 2020-10-02 | 遵义医科大学 | 一种含色酮骨架类多环化合物、制备方法及其应用 |
-
2021
- 2021-01-29 CN CN202110123464.1A patent/CN112898256B/zh active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3265743A (en) * | 1962-05-14 | 1966-08-09 | Ethyl Corp | Production of dihalocarbene adducts |
CA2079373A1 (en) * | 1991-09-30 | 1993-03-31 | Petpiboon Prasit | (azaarylmethoxy)indoles as inhibitors of leukotriene biosynthesis |
AU2010205799A1 (en) * | 2009-01-15 | 2011-07-28 | Syngenta Limited | Novel herbicides |
CN111732567A (zh) * | 2020-06-17 | 2020-10-02 | 遵义医科大学 | 一种含色酮骨架类多环化合物、制备方法及其应用 |
Non-Patent Citations (2)
Title |
---|
WEN-QING ZHU,等: "Palladium-catalyzed [2 + 2 + 1] annulation: access to chromone fused cyclopentanones with cyclopropenone as the CO source", 《ORG. CHEM. FRONT.》 * |
刘文竹等: "环丙烷与不饱和化合物发生[3+2]扩环反应的研究进展", 《有机化学》 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113773294A (zh) * | 2021-09-18 | 2021-12-10 | 武汉大学 | 黄酮、异黄酮类化合物的制备方法及其应用 |
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