CN104311528A - 一种制备色烯衍生物的方法 - Google Patents

一种制备色烯衍生物的方法 Download PDF

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CN104311528A
CN104311528A CN201410466892.4A CN201410466892A CN104311528A CN 104311528 A CN104311528 A CN 104311528A CN 201410466892 A CN201410466892 A CN 201410466892A CN 104311528 A CN104311528 A CN 104311528A
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朱启华
包小波
徐云根
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China Pharmaceutical University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • 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
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • 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
    • C07D311/78—Ring systems having three or more relevant rings
    • C07D311/80—Dibenzopyrans; Hydrogenated dibenzopyrans
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • 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
    • C07D311/94—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 condensed with rings other than six-membered or with ring systems containing such rings
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    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
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    • C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C07D491/052—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being six-membered
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Abstract

本发明涉及有机合成领域。具体涉及色烯衍生物(I)的制备方法。本发明以α,β-不饱和羰基化合物II和2-羟基苯硼酸衍生物III为原料，在钯催化剂存在下，将Suzuki-Miyaura反应和Michael加成反应进行“一锅煮”，制得I。具有原料易得、底物适应范围广、产率高等优点。

Description

一种制备色烯衍生物的方法
技术领域
本发明涉及有机合成领域。具体涉及色烯衍生物的制备方法。
背景技术
色烯，即苯并吡喃，有α-和γ-两个异构体。这两种化合物本身并不重要，但它们的某些衍生物却很重要。例如，6H-苯并色烯类化合物是一类非常重要的含氧杂环化合物。许多天然产物都含有这类结构。比如从大麻中分离出来的屈大麻酚(Tetrahedrocannabinol,(-)-Δ(PPM)9-THC)和屈大麻酚的异构体((-)-Δ(PPM)8-THC)。其中屈大麻酚可以用于治疗癌症、化疗引起的呕吐以及多发性硬化症病人痉挛等疾病(Cannabinoids for cancer treatment:progressand promise.Cancer.Res.2008,68(2):339-342)。为了能够快速构建色烯类化合物库，为进一步研究这类结构潜在的生物活性提供物质基础，寻找方便、高效的合成这类化合物的方法显得尤为重要。
文献报道的6-取代-6H-苯并色烯衍生物的制备方法如下：Tsuda等人(Palladium-CatalyzedOxidatice Cross-Coupling of2-Phenylphenols with Alkenes.Chem.Lett.1997,26(11):1103-1104)报道用联苯酚与烯丙酸酯等在醋酸钯/醋酸铜以及分子筛催化下合成了6-位取代的6H-苯并色烯类化合物。该方法原料为联苯酚类化合物，来源困难；另外，利用该方法无法制备脂肪环并色烯衍生物。
Motti等(Sequential Unsymmetrical Aryl Coupling of o-Substituted Aryl Iodides with o-Bromophenolsand Reaction with Olefins:Palladium-Catalyzed Synthesis of6H-Dibenzopyran Derivatives.Org.Lett.2006,8(18):3967-3970)对上述方法进行了改进，用取代的碘苯，邻溴苯酚以及烯丙酸类在醋酸钯以及降冰片烯(Norbornene)催化下采用“一锅煮”的方法，同样得到了6-位取代的6H-苯并色烯类化合物。但该方法所用原料取代碘苯不易获得，且反应时间长；另外，利用该方法也无法制备脂肪环并色烯衍生物。
发明内容
本发明的目的是寻找一种成本低廉、原料易得的制备色烯衍生物的方法。
本发明公开了一种新的制备方法，包括：
在氮气保护下，将化合物II、III、钯催化剂、碱和溶剂混合，于50℃～120℃反应；反应毕，冷却至室温，抽虑，通过重结晶或柱层析得到色烯衍生物I。
其中：
A为C5-C6环烷烃、芳香环或取代的芳香环；优选环戊烷、环己烷、噻吩、吡啶、苯或取代苯环。
B为芳香环或取代的芳香环；优选苯环、取代苯环或萘环。
R为C1-C6烷基、芳基或烷氧基；优选甲基、苯基或乙氧基。
钯催化剂为四(三苯基膦)钯、[1,1'-双(二苯基膦基)二茂铁]二氯化钯、[1,1'-双(二苯基膦)二茂铁]二氯化钯二氯甲烷络合物、双(二亚芐基丙酮)钯或[双(三苯基磷)]二氯化钯；优选四(三苯基膦)钯。
碱为0.1～5mol/L碳酸钠水溶液，0.1～5mol/L碳酸钾水溶液，0.1～5mol/L氢氧化钠水溶液，0.1～5mol/L氢氧化钾水溶液，N,N-二异丙基乙胺，1,8-二氮杂双环[5.4.0]十一碳-7-烯，三乙胺；优选2mol/L碳酸钠水溶液。
溶剂为乙二醇二甲醚、1,4-二氧六环或N,N-二甲基甲酰胺；优选乙二醇二甲醚。
原料II：III的摩尔比为1:1～1:1.5；优选1:1。
本发明的方法既可制备芳香环并色烯衍生物，也可制备脂肪环并色烯衍生物。与现有文献报道的方法相比，具有底物范围更广，催化剂系统简单，产率较高(75％-100％)等优点。
具体实施方式
实施例1
2-(4-(1,2,3,4-四氢环戊烷[c]并色烯)基)乙酸乙酯(I-1)的合成：
将1-(2-溴环戊烯基)烯丙酸乙酯(0.78mmol)以及2-羟基苯硼酸(0.78mmol)溶解在20ml的乙二醇二甲醚中，向溶液中加入2mol/L的碳酸钠溶液(2ml)以及四(三苯基膦)钯(0.1g,10％mmol)，氮气保护下，加热回流，反应4h后冷却至室温，抽虑，滤液旋干，得粗品，粗品经柱层析(淋洗剂：PE/EA＝15:1)分离得到黄色有状物，产率：80％。
1H-NMR(500MHz,CDCl3),δ(ppm):7.07(td,J1＝1.5Hz,J2＝7.8Hz,1H,ArH),6.93(dd,J1＝1.4Hz,J2＝7.4Hz,1H,ArH),6.85(t,J＝7.4Hz,1H,ArH),6.79(d,J＝8.0Hz,1H,ArH),5.47(t,J＝4.2Hz,1H,CH),4.22(m,2H,CH2),2.77(m,1H,1/2CH2),2.68(m,3H,3/2CH2),2.44(m,2H,CH2),2.07(m,2H,CH2),1.25(t,J＝7.1Hz,3H,CH3).
13C-NMR(75MHz,CDCl3),δ(ppm):133.9,132.1,128.7,123.0,121.2,120.9,115.5,74.2,60.6,39.7,33.0,30.5,22.4,14.1.
HRMS(EI)for(M+H)+:calcd259.1334,found259.1336.
实施例2
2-(4-(8-氟-1,2,3,4-四氢环戊烷[c]并色烯)基)乙酸乙酯(I-2)的合成：
以1-(2-溴环戊烯基)烯丙酸乙酯以及5-氟-2-羟基苯硼酸为原料，操作同实施例1，得到黄色油状物(I-2)，收率：85％。
1H-NMR(500MHz,CDCl3),δ(ppm):6.74(dd,J1＝7.2Hz,J2＝3.7Hz,2H,ArH),6.64(dd,J1＝8.5Hz,J2＝2.5Hz,1H,ArH),5.43(d,J＝6.3Hz,1H,CH),4.18(q,J＝7.1Hz,2H,CH2),2.74(dd,J1＝15.0Hz,J2＝8.4Hz,1H,1/2CH2),2.63(d,J＝4.5Hz,2H,CH2),2.59(dd,J1＝6.7Hz,J2＝3.2Hz,1H,1/2CH2),2.47(t,J＝7.5Hz,2H,CH2),2.07(m,J＝7.5Hz,2H,CH2),1.26(t,J＝7.1Hz,3H,CH3).
13C-NMR(75MHz,CDCl3),δ(ppm):169.8,135.2,131.3,115.8,113.7,113.4,110.2,108.9,73.4,60.2,38.8,32.6,29.9,21.8,13.6.
HRMS(EI)for(M+H)+:calcd277.1240,found277.1241.
实施例3
2-(4-(1,2,3,4-四氢b苯并环戊烷[c]并色烯)基)乙酸乙酯(I-3)的合成：
以1-(2-溴环戊烯基)烯丙酸乙酯以及2-羟基萘硼酸为原料，操作同实施例1，得到黄色油状物(I-3)，收率：81％。
1H-NMR(300MHz,CDCl3),δ(ppm):7.66(d,J＝7.9Hz,1H,ArH),7.61(d,J＝8.0Hz,1H,ArH),7.35(m,2H,ArH),7.25(d,J＝6.8Hz,1H,ArH),7.14(s.1H,ArH),5.49(1H,CH),4.22(q,J＝7.2Hz,2H,CH2),2.80(m,3H,3/2CH2),2.64(d,J＝4.6Hz,1H,1/2CH2),2.14(m,2H,CH2),1.30(t,J＝6.6Hz,3H,CH3).
13C-NMR(75MHz,CDCl3),δ(ppm):170.4,150.0,136.9,134.2,132.3,129.5,127.5,126.4,125.8,123.8,122.3,121.5,110.6,74.2,60.7,39.9,33.4,30.6,22.3,14.1.
HRMS(EI)for(M+H)+:calcd309.1485,found309.1487.
实施例4
2-(6-(7,8,9,10-四氢-6H-苯并色烯)基)乙酸乙酯(I-4)的合成：
以1-(2-溴环己烯基)烯丙酸乙酯以及2-羟基苯硼酸为原料，操作同实施例1得到无色油状物(I-4)，收率：75％。
1H-NMR(300MHz,CDCl3),δ(ppm):7.10(t,J＝7.6Hz,2H,ArH),6.91(t,J＝7.6Hz,1H,ArH),6.80(d,J＝7.9Hz,1H,ArH),5.02(d,J＝9.4Hz,1H,CH),4.21(q,J＝7.2Hz,2H,CH2),2.72(dd,J1＝9.6Hz,J2＝14.9Hz,1H,1/2CH2),2.47(m,1H,1/2CH2),2.26(m,1H,1/2CH2),2.08(m,2H,CH2),1.79(m,3H,3/2CH2),1.69(m,1H,1/2CH2),1.27(t,J＝7.1Hz,3H,CH3).
13C-NMR(75MHz,CDCl3),δ(ppm):129.0,128.1,125.1,123.6,121.9,121.1,116.5,75.0,60.5,38.1,26.5,23.7,22.3,22.1,14.1.
HRMS(EI)for(M+Na)+:calcd295.1307,found295.1305.
实施例5
2-(6-(2-氟-7,8,9,10-四氢-6H-苯并色烯)基)乙酸乙酯(I-5)的合成：
以1-(2-溴环己烯基)烯丙酸乙酯以及5-氟-2-羟基苯硼酸为原料，操作同实施例1得到黄色油状物(I-5)，收率：86％。
1H-NMR(300MHz,CDCl3),δ(ppm):6.85(m,2H,ArH),6.74(m,1H,ArH),5.01(d,J＝9.2Hz,1H,CH),4.21(dd,J1＝6.8Hz,J2＝3.2Hz,2H,CH2),2.72(dd,J1＝9.7Hz,J2＝14.9Hz,1H,1/2CH2),2.47(dd,J1＝3.3Hz,J2＝14.9Hz,1H,1/2CH2),2.34(m,1H,1/2CH2),2.28(m,2H,CH2),2.07(m,2H,CH2),1.77(m,5H,5/2CH2),1.27(t,J＝7.2Hz,3H,CH3).
13C-NMR(75MHz,CDCl3),δ(ppm):170.2,158.8,130.2,124.3,116.7,113.7,113.4,108.3,108.0,74.6,60.2,37.2,25.9,23.2,21.7,21.5,13.7.
实施例6
2-(6-(2,3,4,5-四氢-1H-二苯[c,f]并色烯)基)乙酸乙酯(I-6)的合成：
以1-(2-溴环己烯基)烯丙酸乙酯以及2-羟基萘硼酸为原料，操作同实施例1，得到黄色油状物(I-6)，收率：76％。
1H-NMR(500MHz,CDCl3),δ(ppm):7.72(d,J＝7.8Hz,1H,ArH)7.63(d,J＝7.9Hz,1H,ArH),7.36(m,2H,ArH),7.16(s,1H,ArH),5.07(d,J＝8.4Hz,1H,CH),4.26(m,2H,CH2),2.72(dd,J1＝9.6Hz,J2＝14.9Hz,1H,1/2CH2),2.55(m,2H,CH2),2.41(m,1H,1/2CH2),2.11(m,2H,CH2),1.81(m,4H,2CH2),1.28(t,J＝7.1Hz,3H,CH3).
13C-NMR(75MHz,CDCl3),δ(ppm):170.3,149.1,133.5,131.7,129.1,127.3,125.8,125.4,124.8,124.2,123.3,120.3,111.2,74.6,60.8,38.1,26.2,23.3,21.9,21.6,13.8.
HRMS(EI)for(M+H)+:calcd323.1642,found323.1647.
实施例7
2-(5-(4H-噻吩[2,3-c]色烯)基)乙酸乙酯(I-7)的合成：
以1-(3-溴噻吩)烯丙酸乙酯以及2-羟基苯硼酸为原料，操作同实施例1，得到黄色油状物(I-7)，收率为：92％。
1H-NMR(500MHz,CDCl3),δ(ppm):7.68(m,1H,ArH),7.45(m,1H,ArH),7.28(m,1H,ArH),7.02(m,2H,ArH),5.96(dd,J1＝5.4Hz,J2＝8.0Hz,1H,CH),4.25(q,J＝6.8Hz,2H,CH2),3.06(dd,J1＝8.2Hz,J2＝15.5Hz,1H,1/2CH2),2.86(dd,J1＝5.3Hz,J2＝15.4Hz,1H,1/2CH2),1.31(t,J＝7.1Hz,3H,CH3).
13C-NMR(75MHz,CDCl3),δ(ppm):132.3,131.9,128.5,125.0,123.0,122.3,122.1,120.6,117.2,72.0,60.9,41.4,14.2.
HRMS(EI)for(M+H)+:calcd275.0736,found275.0734.
实施例8
2-(5-(8-氟-4H-噻吩[2,3-c]色烯)基)乙酸乙酯(I-8)的合成：
以1-(3-溴噻吩)烯丙酸乙酯以及5-氟-2-羟基苯硼酸为原料，操作同实施例1，得到黄色油状物(I-8)，收率：93％。
1H-NMR(500MHz,CDCl3),δ(ppm):7.30(d,J＝5.1Hz,1H,ArH),7.23(d,J＝5.2Hz,1H,ArH),7.13(dd,J1＝2.9Hz,J2＝8.6Hz,ArH),6.90(dd,J1＝4.8Hz,J2＝8.9Hz,1H,ArH),6.85(td,J1＝2.9Hz,J2＝8.3Hz,1H,ArH),5.91(dd,J1＝5.4Hz,J2＝8.1Hz,1H,CH),4.25(q,J＝7.2Hz,2H,CH2),3.02(dd,J1＝8.2Hz,J2＝15.6Hz,1H,1/2CH2),2.84(dd,J1＝5.4Hz,J2＝15.6Hz,1H,1/2CH2),1.30(t,J＝7.2Hz,3H,CH3).
13C-NMR(75MHz,CDCl3),δ(ppm):169.6,159.0,157.1,133.8,128.6,125.3,122.3,114.7,110.6,110.4,72.1,60.9,41.1,30.8,14.1.
HRMS(EI)for(M+H)+:calcd293.0642,found293.0640.
实施例9
2-(5-(4H-苯[g]噻吩[2,3-c]色烯)基)乙酸乙酯(I-9)的合成：
以1-(3-溴噻吩)烯丙酸乙酯和2-羟基萘硼酸为原料，操作同实施例1，得到无色油状物(I-9)，收率：90％。
1H-NMR(300MHz,CDCl3),δ(ppm):7.86(s,1H,ArH),7.77(d,J＝8.1Hz,1H,ArH),7.67(d,J＝8.1Hz,1H,ArH),7.45(d,J＝5.1Hz,1H,ArH),7.43(m,4H,ArH),5.99(dd,J1＝8.1Hz,J2＝5.4Hz,1H,CH),4.27(q,J1＝7.1Hz,2H,CH2),3.07(dd,J1＝15.6Hz,J2＝8.1Hz,1H,1/2CH2),2.88(dd,J1＝15.6Hz,J2＝5.4Hz,1H,1/2CH2),1.32(t,J＝7.2Hz,3H,CH3).
13C-NMR(75MHz,CDCl3),δ(ppm):169.7,134.1,133.9,132.3,129.8,127.6,126.7,126.1,125.2,124.4,122.2,121,5,72.1,60.9,41.6,29.6,14.2.
HRMS(EI)for(M+H)+:calcd325.0893,found325.0899.
实施例10
2-(5-(5H-色烯[4,3-b]吡啶)基)乙酸乙酯(I-10)的合成：
以1-(2-溴吡啶基)烯丙酸乙酯以及2-羟基苯硼酸为原料，操作同实施例1，得到无色油状物(I-10)，收率：90％。
1H-NMR(500MHz,CDCl3),δ(ppm):8.61(s,1H,ArH),8.24(d,J＝6.4Hz,1H,ArH),7.49(d,J＝6.6Hz,1H,ArH),7.35(m,1H,ArH),7.22(m,1H,ArH),7.14(t,J＝7.1Hz,1H,ArH),6.97(d,J＝7.5Hz,1H,ArH),5.80(dd,J1＝5.9Hz,J2＝7.7Hz,1H,CH),4.20(q,J＝6.9Hz,2H,CH2),3.04(dd,J1＝8.3Hz,J2＝15.3Hz,1H,1/2CH2),2.76(dd,J1＝5.6Hz,J2＝15.2Hz,1H,1/2CH2),1.28(t,J＝7.0Hz,3H,CH3).
13C-NMR(75MHz,CDCl3),δ(ppm):169.8,154.0,149.6,147.7,132.4,131.5,127.9,124.5,122.5,122.3,117.6,73.8,60.9,40.1,14.1.
HRMS(EI)for(M+H)+:calcd270.1125,found270.1123.
实施例11
2-(5-(9-氟-5H-色烯[4,3-b]吡啶)基)乙酸乙酯(I-11)的合成：
以1-(2-溴吡啶基)烯丙酸乙酯以及5-氟-2-羟基苯硼酸为原料，操作同实施例1，粗产物经石油醚和乙酸乙酯混合溶剂重结晶后得到黄色固体(I-11)，收率：89％，m.p.74～76℃。
1H-NMR(500MHz,CDCl3),δ(ppm):8.60(dd,J1＝4.9Hz,J2＝1.6Hz,1H,ArH),7.92(dd,J1＝9.0Hz,J2＝3.1Hz,1H,ArH),7.54(m,1H,ArH),7.23(dd,J1＝7.7Hz,J2＝4.8Hz,1H,ArH),7.07(m,1H,ArH),6.90(dd,J1＝8.9Hz,J2＝4.6Hz,1H,ArH),5.76(dd,J1＝8.2Hz,J2＝5.7Hz,1H,CH),4.19(q,J＝7.1Hz,2H,CH2),2.99(dd,J1＝15.3Hz,J2＝8.3Hz,1H,1/2CH2),2.73(dd,J1＝15.3Hz,J2＝5.7Hz,1H,1/2CH2),1.26(t,J＝7.1Hz,3H,CH3).
13C-NMR(75MHz,CDCl3),δ(ppm):169.2,159.4,156.3,149.2,131.9,127.5,122.6,118.4,117.8,117.4,110.3,110.9,73.3,60.5,39.4,13.6.
HRMS(EI)for(M+H)+:calcd288.103,found288.1031.
实施例12
2-(5-(5H-苯[6,7]色烯[4,3-b]吡啶)基)乙酸乙酯(I-12)的合成：
以1-(2-溴吡啶基)烯丙酸乙酯以及2-羟基萘硼酸为原料，操作同实施例1，粗产物经石油醚和乙酸乙酯混合溶剂重结晶后得到黄色固体(I-12)，收率91％，m.p.72～74℃。
1H-NMR(500MHz,CDCl3),δ(ppm):8.77(s,1H,ArH),8.67(dd,J1＝4.8Hz,J2＝1.7Hz,1H,ArH),7.92(d,J＝8.2Hz,1H,ArH),7.71(d,J＝8.1Hz,1H,ArH),7.53(dd,J1＝7.6Hz,J2＝1.6Hz,1H,ArH),7.51(m,3H),7.23(dd,J1＝7.7Hz,J2＝4.7Hz,1H,ArH),5.81(dd,J1＝8.1Hz,J2＝5.8Hz,1H,CH),4.20(q,J＝7.2Hz,2H,CH2),3.00(dd,J1＝15.4Hz,J2＝8.2Hz,1H,1/2CH2),2.75(dd,J1＝15.4Hz,J2＝5.7Hz,1H,1/2CH2),1.26(t,J1＝7.1Hz,3H,CH3).
13C-NMR(75MHz,CDCl3),δ(ppm):169.8,151.2,149.8,147.6,135.5,132.8,129.9,129.4,128.9,127.2,126.6,124.7,124.6,122.7,113.2,73.8,60.9,40.5,29.6,14.1.
HRMS(EI)for(M+H)+:calcd320.1281,found320.1285.
实施例13
2-(6-(2-氟-6H-苯并色烯)基)乙基苯基酮(I-13)的合成：
以1-(2-溴苯基)烯丙基甲基酮以及5-氟-2-羟基苯硼酸为原料，操作同实施例1，粗产物经石油醚和乙酸乙酯混合溶剂重结晶后得到白色固体(I-13)，收率：90％，m.p.84～86℃。
1H-NMR(300MHz,CDCl3),δ(ppm):7.66(dd,J1＝1.5Hz,J2＝7.8Hz,1H,ArH),7.39(dd,J1＝2.5Hz,J2＝9.8Hz,1H,ArH),7.28(m,2H,ArH),7.14(t,J＝5.5Hz,1H,ArH),7.08(m,1H,ArH),6.98(m,2H,ArH),5.71(dd,J1＝5.3Hz,J2＝8.1Hz,1H,CH),3.13(dd,J1＝8.1Hz,J2＝16.1Hz,1H,1/2CH2),2.73(dd,J1＝5.3Hz,J2＝16.1Hz,1H,1/2CH2),2.15(s,3H,CH3).
13C-NMR(75MHz,CDCl3),δ(ppm):205.0,159.3,156.1,133.1,128.1,124.2,122.0,118.7,118.6,115.8,115.5,110.2,108.8,73.1,47.5,30.4.
HRMS(EI)for(M+Na)+:calcd279.0792,found279.0799.
实施例14
1-(5-(5H-二苯基[c,g]色烯)基)丙基-2-酮(I-14)的合成：
以1-(2-溴苯基)烯丙基甲基酮以及2-羟基萘硼酸为原料，操作同实施例1，粗产物经石油醚和乙酸乙酯混合溶剂重结晶后得到白色固体(I-14)，收率：93％，m.p.74～76℃。
1H-NMR(300MHz,CDCl3),δ(ppm):8.26(s,1H,ArH),8.01(d,J＝7.7Hz,1H,ArH),7.91(d,J＝7.9Hz,1H,ArH),7.77(d,J＝8.1Hz,1H,ArH),7.50(m,2H,ArH),7.41(m,2H,ArH),7.30(m,2H,ArH),5.80(dd,J1＝4.9Hz,J2＝8.6Hz,1H,CH),3.16(dd,J1＝8.6Hz,J2＝16.1Hz,1H,1/2CH2),2.75(dd,J1＝4.9Hz,J2＝16.1Hz,1H,1/2CH2),2.16(s,3H,CH3).
13C-NMR(75MHz,CDCl3),δ(ppm):205.2,150.0,134.6,134.2,129.5,128.6,128.2,127.8,127.6,127.2,126.2,125.8,124.5,124.0,122.7,122.0,112.9,73.2,48.0,28.9.
HRMS(EI)for(M+Na)+:calcd311.1040,found311.1042.
实施例15
2-(6-(2-氟-8,9-二甲氧基-6H-苯并色烯)基)丙基-2-酮(I-15)的合成：
以1-(4,5-二甲氧基-2-溴苯基)烯丙基甲基酮以及5-氟-2-羟基苯硼酸为原料，操作同实施例1，粗产物经石油醚和乙酸乙酯混合溶剂重结晶后得到黄色固体(I-15)，收率：90％，m.p.128～130℃。
1H-NMR(500MHz,CDCl3),δ(ppm):7.32(d,J＝9.3Hz,1H,ArH),7.09(s,1H,ArH),6.88(t,J＝5.3Hz,2H,ArH),6.69(s,1H,ArH),5.67(dd,J1＝5.2Hz,J2＝8.1Hz,1H,CH),3.96(s,3H,CH3),3.90(s,3H,CH3),3.13(dd,J1＝8.2Hz,J2＝16.0Hz,1H,1/2CH2),2.71(dd,5.2Hz,J1＝5.2Hz,J2＝16.0Hz,1H,1/2CH2),2.16(s,3H,CH3).
13C-NMR(75MHz,CDCl3),δ(ppm):205.4,159.3,149.1,148.8,146.8,125.9,122.9,122.8,120.3,118.5,114.6,114.3,108.5,108.4,105.0,55.6,47.7,30.5.
HRMS(EI)for(M+Na)+:calcd339.1003,found339.1007.
实施例16
2-(5-(2,3-二甲氧基-5H-二苯基[c,g]色烯)基)丙基-2-酮(I-16)的合成：
以1-(4,5-二甲氧基-2-溴苯基)烯丙基甲基酮以及2-羟基萘硼酸为原料，操作同实施例1，粗产物经石油醚和乙酸乙酯混合溶剂重结晶后得到白色固体(I-16)，收率：90％，m.p.100～102℃。
1H-NMR(300MHz,CDCl3),δ(ppm):8.07(s,1H,ArH),7.85(d,J＝7.8Hz,1H,ArH),7.71(d,J＝7.6Hz,1H,ArH),7.43(m,4H,ArH),5.74(t,J＝7.3Hz,1H,CH),4.03(s,3H,CH3),3.92(s,3H,CH3),3.15(dd J1＝8.2Hz,J2＝15.9Hz,1H,1/2CH2),2.72(dd,J1＝4.9Hz,J2＝15.9Hz,1H,1/2CH2),2.15(s,3H,CH3).
13C-NMR(75MHz,CDCl3),δ(ppm):205.5,149.3,148.9,133.6,129.5,127.4,127.3,126.1,125.8,123.9,122.6,121.0,120.7,112.8,108.5,105.5,73.1,55.7,48.4,30.6,29.2；
HRMS(EI)for(M+Na)+:calcd371.1254,found371.1259.
实施例17
2-(6-(6H-苯并色烯)基)乙基苯基酮(I-17)的合成
以1-(2-溴苯基)烯丙基苯基酮以及2-羟基苯硼酸为原料，操作同实施例1，得到黄色油状物(I-17)，收率：95％。
1H-NMR(500MHz,CDCl3),δ(ppm):7.87(d,J＝10.0Hz,2H,ArH),7.74(t,J＝5.75Hz,2H,ArH),7.53(td,J1＝5.8Hz,J2＝7.4Hz,1H,ArH),7.40(m,3H,ArH),7.28(t,J＝7.6Hz,1H,ArH),7.23(m,2H,ArH),7.06(t,J＝7.6Hz,1H,ArH),5.97(t,J＝5.4Hz,1H,CH),3.73(dd,J1＝7.8Hz,J2＝16.2Hz,1H,1/2CH2),3.21(dd,J1＝5.4Hz,J2＝16.2Hz,1H,1/2CH2).
13C-NMR(75MHz,CDCl3),δ(ppm):197.1,152.3,136.9,133.8,133.2,129.7,129.0,128.6,128.5,128.3,127.9,125.1,123.1,122.3,122.2,118.4,73.4,43.5.
HRMS(EI)for(M+Na)+:calcd323.103,found323.1038.
实施例18
2-(6-(8,9-二甲氧基-6H-苯并色烯)基)乙基苯基酮(I-18)的合成
以1-(4,5-二甲氧基-2-溴苯基)烯丙基苯基酮以及2-羟基苯硼酸为原料，操作同实施例1，粗产物经石油醚和乙酸乙酯混合溶剂重结晶后得到黄色固体(I-18)，收率：95％，m.p.148～150℃。
1H-NMR(500MHz,CDCl3),δ(ppm):7.85(m,2H,ArH),7.67(dd,J1＝1.6Hz,J2＝7.6Hz,1H,ArH),7.56(t,J＝7.32Hz,1H,ArH),7.41(t,J＝6.6Hz,1H,ArH),7.30(m,1H,ArH),7.20(m,2H,ArH),7.07(m,1H,ArH),6.85(d,J＝7.2Hz,1H,ArH),6.74(s,1H,ArH),5.93(dd,J1＝5.7Hz,J2＝7.3Hz,1H,CH),3.95(s,3H,CH3),3.86(s,3H,CH3),3.72(dd,J1＝7.3Hz,J2＝16.1Hz,1H,1/2CH2),3.21(dd,J1＝5.6Hz,J2＝16.1Hz,1H,1/2CH2).
13C-NMR(75MHz,CDCl3),δ(ppm):197.5,151.5,149.3,136.9,133.3,131.4,129.7,128.7,128.5,128.2,126.5,124.3,122.3,122.2,122.1,121.6,121.4,118.2,116.8,108.4,73.8,56.1,47.8,29.7.
HRMS(EI)for(M+Na)+:calcd383.1254,found383.1244.
实施例19
2-(6-(2-氟-6H-苯并色烯)基)乙基苯基酮(I-13)的合成：
将1-(2-溴苯基)烯丙基甲基酮(0.78mmol)以及5-氟-2-羟基苯硼酸(0.78mmol)溶解在20ml的乙二醇二甲醚中，向溶液中加入1,8-二氮杂双环[5.4.0]十一碳-7-烯(1.54mmol,0.2ml)以及四(三苯基膦)钯(0.1g,10％mmol)，氮气保护下，加热回流，反应12h后冷却至室温，抽虑，滤液旋干，得粗品，粗品经柱层析(淋洗剂：PE/EA＝15:1)分离得到黄色有状物，产率：82％。
实施例20
2-(5-(2,3-二甲氧基-5H-二苯基[c,g]色烯)基)丙基-2-酮(I-16)的合成
将1-(4,5-二甲氧基-2-溴苯基)烯丙基甲基酮(0.78mmol)以及2-羟基萘硼酸(0.78mmol)溶解在20ml的N,N-二甲基甲酰胺中，向溶液中加入2mol/L的碳酸钠溶液(2ml)以及四(三苯基膦)钯(0.1g,10％mmol)，氮气保护下，加热至120℃，反应8h后冷却至室温，抽虑，滤液旋干，得粗品，粗品经柱层析(淋洗剂：PE/EA＝15:1)分离得到黄色有状物，产率：85％。
实施例21
2-(6-(8,9-二甲氧基-6H-苯并色烯)基)乙基苯基酮(I-18)的合成
将1-(4,5-二甲氧基-2-溴苯基)烯丙基苯基酮(0.78mmol)以及2-羟基苯硼酸(0.78mmol)溶解在20ml的乙二醇二甲醚中，向溶液中加入2mol/L的碳酸钠溶液(2ml)以及[1,1'-双(二苯基膦基)二茂铁]二氯化钯(0.057g,10％mmol)，氮气保护下，加热回流，反应24h后冷却至室温，抽虑，滤液旋干，得粗品，粗品经柱层析(淋洗剂：PE/EA＝15:1)分离得到黄色有状物，产率：80％。

Claims (10)

1.一种色烯衍生物(I)的制备方法，包括：
在氮气保护下，将化合物II、III、钯催化剂、碱和溶剂混合，于100℃反应4h；反应毕，冷却至室温，抽虑，通过重结晶或柱层析得到色烯衍生物(I)，
其中，A为C5-C6环烷烃、芳香环或取代的芳香环；B为芳香环或取代的芳香环；R为C1-C6烷基、芳基或烷氧基；
钯催化剂为四(三苯基膦)钯、[1,1'-双(二苯基膦基)二茂铁]二氯化钯、[1,1'-双(二苯基膦)二茂铁]二氯化钯二氯甲烷络合物或双(二亚芐基丙酮)钯或[双(三苯基磷)]二氯化钯。
2.权利要求1的制备方法，其中A为环戊烷、环己烷、噻吩、吡啶、苯或取代苯环。
3.权利要求1的制备方法，其中B为苯环、取代苯环或萘环。
4.权利要求1的制备方法，其中R为甲基、苯基或乙氧基。
5.权利要求1的制备方法，其中催化剂为四(三苯基膦)钯。
6.权利要求1的制备方法，其中II：III的摩尔比为1:1～1:1.5。
7.权利要求1的制备方法，其中溶剂为乙二醇二甲醚、1,4-二氧六环或N,N-二甲基甲酰胺。
8.权利要求7的制备方法，其中溶剂为乙二醇二甲醚。
9.权利要求1的制备方法，其中碱为0.1～5mol/L碳酸钠水溶液、0.1～5mol/L碳酸钾水溶液、0.1～5mol/L氢氧化钠水溶液、0.1～5mol/L氢氧化钾水溶液、N,N-二异丙基乙胺、1,8-二氮杂双环[5.4.0]十一碳-7-烯或三乙胺。
10.权利要求9的制备方法，其中碱为2mol/L碳酸钠水溶液。
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105693681A (zh) * 2015-12-23 2016-06-22 上海大学 三氟甲基色烯衍生物及其合成方法

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Application publication date: 20150128