一类二芳基甲烷卤代烯烃衍生物及制备方法与流程

文档序号:17917840发布日期:2019-06-14 23:54

本发明涉及化工技术领域,具体涉及一类二芳基甲烷卤代烯烃衍生物及铁催化三组分反应制备该类衍生物的方法。



背景技术:

二芳基甲烷及含二芳基甲烷结构化合物在许多天然产物,以及药物分子广泛存在,如下所示,同时该类结构也是一类很重要的有机合成砌块,在合成有机化学中应用广泛。

因此,利用廉价易得的催化剂催化简单的原料合成含二芳基甲烷结构化合物,这无论对于有机合成化学还是工业生产都具有很重要的意义,同时也为合成各种含有二芳基甲烷结构的天然产物及药物中间体提供了一种新的方法。与此同时这种方法的通用性使得能够合成大量的结构相似性的分子,建立化合物库,为进行活性分子的筛选奠定了基础。从原子经济性,步骤经济性和绿色环保,减少废弃物排放的角度出发,通过溴化铁催化的p-QMs(p-quinodimethane)参与的三组分反应无疑对化学家们具有相当大的吸引力。人们知道,p-QMs是经典的多π共轭体系不饱和酮化合物,因此很容易发生芳构化生成二芳基甲烷化合物。因此关于p-QMs与各种亲核试剂发生亲核加成合成含二芳基甲烷骨架化合物吸引了化学家的注意。但据人们所知,目前研究报道中亲核试剂较多的为sp2,sp3碳以及一些杂原子,而对于sp碳作为亲核试剂与p-QMs发生反应的报道目前仅有一例,对于底物的普适性具有很大的局限性。



技术实现要素:

本发明的目的是针对现有技术sp碳作为亲核试剂与p-QMs发生反应对底物的普适性具有很大局限性的这一不足而提供一种铁催化的p-QMs,苯乙炔及卤素的三组分反应方法合成一类二芳基甲烷卤代烯烃衍生物,该方法条件温和,原料廉价易得,使用范围广,生成的产物可以用来合成一些具有显著活性的分子。

实现本发明目的的具体技术方案是:

一类二芳基甲烷卤代烯烃衍生物,该类衍生物具有下式所示结构:

其中,R1为叔丁基或异丙基;

R2为芳基、取代芳基、叔丁基或异丙基;

R3为芳基、取代芳基、噻吩或二茂铁;

X为氟、氯、溴或碘。

一种上述的二芳基甲烷卤代烯烃衍生物的制备方法,特点在于,在氮气保护下,p-QMs和苯乙炔先溶解在甲苯中,然后加入到溴化铁催化剂中,50℃搅拌6-12h,制得所述二芳基甲烷卤代烯烃衍生物;具体制备过程如下式所示:

式(Ⅰ)中,化合物1即p-QMs与化合物2即苯乙炔的摩尔比为1∶2;反应中所用的溴化铁作为催化剂参与反应,溴化铁用量为p-QMs物质的量的40mol%;

R1为叔丁基;

R2为苯基、取代苯基、叔丁基或异丙基;

R3为苯基、取代苯基、噻吩或二茂铁。

一种上述的二芳基甲烷卤代烯烃衍生物的制备方法,特点在于,将p-QMs和苯乙炔先溶解在甲苯中,然后加入到溴化铁催化剂中,再加入的氢卤酸化合物,室温搅拌3-12h,制得所述二芳基甲烷卤代烯烃衍生物;具体制备过程如下式所示:

式(Ⅱ)中,其化合物1即p-QMs与化合物2即苯乙炔的摩尔比为1∶2;反应中所用的溴化铁作为催化剂参与反应,氢卤酸作为卤素源参与反应,溴化铁用量为p-QMs物质量的5mol%,氢溴酸用量为p-QMs物质量的2倍;

所述式(Ⅱ)中:R1为叔丁基或异丙基;

R2为苯基、取代苯基、叔丁基或异丙基;

R3为苯基、取代苯基、噻吩或二茂铁;

X为氟、氯、溴或碘。

本发明式(Ⅱ)所示的二芳基甲烷卤代烯烃,具体包括:

其反应路线如下:

本发明制备方法,以廉价的金属溴化铁为催化剂,在有机溶剂中p-QMs,苯乙炔及卤素的三组分反应,制得式(Ⅰ),式(Ⅱ)所示的二芳基甲烷卤代烯烃。

本发明致力于通过发展新的方法实现对二芳基甲烷化合物的合成。本发明通过金属催化剂和溶剂的筛选,在温和条件下良好收率的得到了三组分反应的二芳基甲烷卤代烯烃。本发明制备方法中,苯乙炔首先作为亲核试剂进攻p-QMs发生亲核加成,随后卤素作为亲核试剂发生第二次亲核加成。一锅法三组分的得到二芳基甲烷卤代烯烃,同时该反应对于氢氟酸、氢氯酸、氢溴酸、氢碘酸都能很好的适用。

本发明制备方法可快速高效合成含有二芳基甲烷卤代烯烃衍生物,例如,以p-QMs,苯乙炔化合物为原料,在铁催化剂的存在下,以甲苯为溶剂,与发生三组分反应,具有催化剂用量少,条件温和,底物适用广等特点。本发明制备方法的有益效果还包括反应时间短,能够放大到克级规模。

具体实施方式

结合以下具体实施例,对本发明作进一步的详细说明,本发明的保护内容不局限于以下实施例。在不背离发明构思的精神和范围下,本领域技术人员能够想到的变化和优点都被包括在本发明中,并且以所附的权利要求书为保护范围。实施本发明的过程、条件、试剂、实验方法等,除以下专门提及的内容之外,均为本领域的普遍知识和公知常识,本发明没有特别限制内容。

实施例1

4-(3-bromo-1,3-bis(4-methoxyphenyl)allyl)-2,6-di-tert-butylphenol的合成

式(Ⅰ):

第一步:向一个预先干燥过的反应管中,在氮气保护下加入FeBr3(0.04mmol)和预先用CaH2干燥过少量的Toluene(2mL),随后称量对甲氧基p-QM(0.1mmol)),苯乙炔(0.02mmol),溶于1mL干燥过的甲苯中。

第二步,将p-QM,苯乙炔的混合溶液加入到盛有FeBr3的反应管,并用甲苯把混合溶液瓶子洗干净。然后在保护下50℃加热8小时,TLC检测,反应结束,直接旋干,柱层析分离纯化,得到二芳基甲烷卤代烯烃衍生物,收率为76%。

式(Ⅱ):

第一步:向一个预先干燥过的反应管中,加入FeBr3(0.005mmol)和预先用CaH2干燥过少量的Toluene(2mL),随后称量对甲氧基p-QM(0.1mmol)),苯乙炔(0.02mmol),溶于1mL干燥过的甲苯中。

第二步,将p-QM,苯乙炔的混合溶液加入到盛有FeBr3的反应管,并用甲苯把混合溶液瓶子洗干净。用注射器加入HBr(0.2mmol%),室温下搅拌3-12h。TLC检测,反应结束,直接旋干,柱层析分离纯化,得到二芳基甲烷卤代烯烃衍生物,收率为86%..1H NMR(500MHz,CDCl3)δ7.33(d,J=8.6Hz,2H),7.11(d,J=8.5Hz,2H),6.89(dd,J=10.2,9.4Hz,6H),6.63(d,J=10.9Hz,1H),5.13(s,1H),4.61(d,J=10.9Hz,1H),3.85(s,3H),3.82(s,3H),1.42(s,18H).;13C NMR(125MHz,CDCl3)δ159.6,158.0,152.3),136.2,135.8,135.4,133.8,131.0,130.3,129.1,124.6,120.3,113.8,113.6,55.3,55.2,50.8,34.3,30.3.;HRMS(ESI)m/z calculated for C31H37BrNaO3=559.1818,found=559.1828。

实施例2

4-(3-bromo-3-(4-methoxyphenyl)-1-phenylallyl)-2,6-di-tert-butylphenol的合成

操作参考实施例1收率为式(Ⅰ)条件66%.式(Ⅱ)条件83%;1H NMR(500MHz,CDCl3)δ7.35(t,J=7.4Hz,4H),7.30–7.16(m,3H),6.91(d,J=8.0Hz,4H),6.68(d,J=10.9Hz,1H),5.15(s,1H),4.67(d,J=10.9Hz,1H),3.86(s,3H),1.43(s,18H).;13C NMR(125MHz,CDCl3)δ159.6,152.3,143.3,135.9,135.8,133.5,130.9,130.3,128.5,128.1,126.4,124.7,120.6,113.6,55.3,51.6,34.3,30.2.;HRMS(ESI)m/z calculated for C30H35BrNaO2=589.1712,found=589.1719。

实施例3

4-(3-bromo-3-(4-methoxyphenyl)-1-(p-tolyl)allyl)-2,6-di-tert-butylphenol的合成

操作参考实施例1收率为式(Ⅰ)条件为85%,式(Ⅱ)条件87%.1H NMR(500MHz,CDCl3)δ7.30(d,J=8.6Hz,2H),7.12(d,J=7.9Hz,2H),7.05(d,J=7.9Hz,2H),6.88(d,J=10.2Hz,4H),6.61(d,J=10.9Hz,1H),5.10(s,1H),4.59(d,J=10.9Hz,1H),3.83(s,3H),2.34(s,3H),1.39(s,18H).;13C NMR(125MHz,CDCl3)δ159.6,152.3,140.3,136.1,135.9,135.8,133.6,131.0,130.3,129.2,128.0,124.7,120.4,113.6,55.3,51.2,34.4,30.3,21.0.;HRMS(ESI)m/z calculated for C31H37BrNaO2=543.1869,found=543.1872。

实施例4

4-(1-(4-(benzyloxy)phenyl)-3-bromo-3-(4-methoxyphenyl)allyl)-2,6-di-tert-butylphenol的合成

操作参考实施例1收率式(Ⅰ)条件为85%,式(Ⅱ)条件87%..1H NMR(500MHz,CDCl3)δ7.45(d,J=7.3Hz,2H),7.40(t,J=7.5Hz,2H),7.37–7.29(m,3H),7.09(d,J=8.5Hz,2H),6.94(d,J=8.5Hz,2H),6.89(d,J=6.6Hz,4H),6.61(d,J=10.9Hz,1H),5.12(s,1H),5.07(s,2H),4.60(d,J=10.9Hz,1H),3.84(s,3H),1.41(s,18H).;13C NMR(125MHz,CDCl3)δ159.6,157.3,152.3,137.0,136.2,135.7,133.7,131.0,130.3,129.1,128.5,127.9,127.5,124.6,120.4,114.8,113.6,70.0,55.3,50.8,34.4,30.3.;HRMS(ESI)m/z calculated for C37H41BrNaO3=635.2131,found=635.2139。

实施例5

4-(3-bromo-1-(2-methoxyphenyl)-3-(4-methoxyphenyl)allyl)-2,6-di-tert-butylphenol的合成

操作参考实施例1收率为式(Ⅰ)条件为63%,式(Ⅱ)条件69%..1H NMR(500MHz,CDCl3)δ7.28(s,1H),7.24–7.15(m,2H),6.98–6.89(m,3H),6.85(dd,J=8.3,6.2Hz,3H),6.69(d,J=10.9Hz,1H),5.04(s,1H),5.01(d,J=10.9Hz,1H),3.83(s,3H),3.67(s,3H),1.38(s,18H).;13C NMR(125MHz,CDCl3)δ159.5,156.8,152.0,135.5,135.4,133.3,131.7,131.2,130.4,129.0,127.6,124.5,120.8,120.7,113.3,111.0,55.3,55.3,45.4,34.3,30.3.;HRMS(ESI)m/z calculated for C31H37BrNaO3=559.1818,found=559.1823。

实施例6

4-(3-bromo-1-(6-methoxynaphthalen-2-yl)-3-(4-methoxyphenyl)allyl)-2,6-di-tert-butylphenol的合成

操作参考实施例1收率为式(Ⅰ)条件为59%,式(Ⅱ)条件91%.1H NMR(500MHz,CDCl3)δ7.74(d,J=8.9Hz,1H),7.69(d,J=8.5Hz,1H),7.61(s,1H),7.35(d,J=8.4Hz,2H),7.24(d,J=8.5Hz,1H),7.17(d,J=8.9Hz,1H),7.15(s,1H),6.95(s,2H),6.90(d,J=8.4Hz,2H),6.73(d,J=10.8Hz,1H),5.14(s,1H),4.78(d,J=10.8Hz,1H),3.94(s,3H),3.84(s,3H),1.41(s,18H).;13C NMR(125MHz,CDCl3)δ159.7,157.5,152.4,138.6,135.9,135.9,133.6 133.2,131.0,130.3,129.3,129.0,127.3,127.0,126.1,124.8,120.7,118.7,113.6,105.6,55.3,51.6,34.4,30.3.;HRMS(ESI)m/z calculated for C35H39BrNaO3=609.1975,found=609.1984。

实施例7

4-(1-bromo-1-(4-methoxyphenyl)-4,4-dimethylpent-1-en-3-yl)-2,6-di-tert-butylphenol的合成

操作参考实施例1收率为式(Ⅰ)条件为67%,式(Ⅱ)条件63%.1H NMR(500MHz,CDCl3)δ7.18(d,J=8.6Hz,2H),6.84(d,J=7.4Hz,4H),6.63(d,J=11.4Hz,1H),5.08(s,1H),3.84(s,3H),2.99(d,J=11.4Hz,1H),1.46(s,18H),0.81(s,9H).;13C NMR(125MHz,CDCl3)δ159.3,152.0,135.1,134.8,132.2,131.6,130.4,125.6,120.3,113.2,57.1,55.2,34.7,34.3,30.4,27.7.;HRMS(ESI)m/z calculated for C28H39BrNaO2=509.2026,found=509.2029。

实施例8

(Z)-4-(3-bromo-3-(4-ethoxyphenyl)-1-(4-methoxyphenyl)allyl)-2,6-di-tert-butylphenol的合成

操作参考实施例1收率为式(Ⅰ)条件为72%,式(Ⅱ)条件80%.1H NMR(500MHz,CDCl3)δ7.29(d,J=8.6Hz,2H),7.08(d,J=8.6Hz,2H),6.88(s,2H),6.87–6.83(m,4H),6.59(d,J=10.9Hz,1H),5.10(s,1H),4.58(d,J=10.9Hz,1H),4.05(q,J=7.0Hz,2H),3.81(s,3H),1.43(t,J=7.0Hz,3H),1.39(s,18H).;13C NMR(125MHz,CDCl3)δ159.0,158.0,152.2,136.1,135.8,135.5,133.8,130.8,130.3,129.1,124.6,120.4,113.94,113.4,63.5,55.2,50.8,34.3,30.3,14.8.;HRMS(ESI)m/z calculated for C32H39BrNaO3=573.1975,found=573.1994。

实施例9

4-(3-bromo-1-(4-methoxyphenyl)-3-(thiophen-2-yl)allyl)-2,6-di-tert-butylphenol的合成

操作参考实施例1收率为式(Ⅰ)条件为76%,式(Ⅱ)条件60%.1H NMR(500MHz,CDCl3)δ7.37(d,J=5.1Hz,1H),7.14(t,J=6.8Hz,3H),7.02–6.97(m,1H),6.94(s,2H),6.88(d,J=8.4Hz,2H),6.65(d,J=10.8Hz,1H),5.13(s,1H),4.94(d,J=10.8Hz,1H),3.82(s,3H),1.41(s,18H).;13C NMR(125MHz,CDCl3)δ158.1,152.4,140.2,138.3,135.9,135.0,133.4,129.18(s),128.8,127.1,126.7,124.7,113.9,112.4,55.2,51.1,34.4,30.3.;HRMS(ESI)m/z calculated for C28H33BrNaO2S=535.1277,found=535.1281。

实施例10

4-(3-bromo-1-(4-methoxyphenyl)-3-(ferroceneyl)allyl)-2,6-di-tert-butylphenol的合成

操作参考实施例1收率为式(Ⅰ)条件为46%,式(Ⅱ)条件54%.1H NMR(500MHz,CDCl3)δ7.18(d,J=7.2Hz,2H),7.01(s,2H),6.87(d,J=7.3Hz,2H),6.43(d,J=9.1Hz,1H),5.17(d,J=9.0Hz,1H),5.11(s,1H),4.55(s,2H),4.26(s,2H),4.18(s,5H),3.81(s,3H),1.42(s,18H).;13C NMR(125MHz,CDCl3)δ158.0,152.3,135.7,135.2,133.7,129.4,129.2,124.8,123.5,113.8,69.7,69.0,68.2,67.6,55.2,51.9,34.4,30.3.;HRMS(ESI)m/z calculated for C34H39BrFeO2=614.1477,found=614.1479。

实施例11

4-(3-bromo-1,3-bis(4-nitrophenyl)allyl)-2,6-di-tert-butylphenol的合成

操作参考实施例1收率为式(Ⅰ)条件为41%,式(Ⅱ)条件56%.1H NMR(500MHz,CDCl3)δ8.24(d,J=8.7Hz,2H),8.19(t,J=9.2Hz,1H),7.64(d,J=8.8Hz,1H),7.49(d,J=8.7Hz,2H),7.30(d,J=8.7Hz,2H),6.81(s,2H),6.77(d,J=10.9Hz,1H),5.22(s,1H),4.60(d,J=10.9Hz,1H),1.39(s,18H).;13C NMR(125MHz,CDCl3)δ153.1,150.2,147.8,146.8,144.4,136.7,133.0,131.3,129.8,128.8,124.4,124.0,123.5,118.7,51.6,34.4,30.2.;HRMS(ESI)m/z calculated for C29H31BrNaN2O5=589.1308,found=589.1312。

实施例12

4-(3-bromo-1,3-bis(4-methoxyphenyl)allyl)-2,6-diisopropylphenol的合成

操作参考实施例1收率为(Ⅰ)条件为0,式(Ⅱ)条件77%.1H NMR(500MHz,CDCl3)δ7.59–7.50(m,1H),7.40–7.22(m,5H),7.17(d,J=7.4Hz,1H),6.96(s,1H),6.93–6.85(m,2H),6.80(s,1H),{6.65(d,J=10.9Hz,0.45H),6.58(d,J=9.4Hz,0.55H)},{5.29(d,J=9.4Hz,0.57H),4.67(d,J=10.9Hz,0.43H)},{4.74(s,0.53H),4.73(s,0.47H)},{3.86(s,1.3H),3.85(s,1.7H)},3.15(dq,J=13.4,6.8Hz,2H),1.26(t,J=4.1Hz,9H),1.25(d,J=2.1Hz,3H).;13C NMR(125MHz,CDCl3)δ159.8,159.7,148.7,148.6,143.5,143.3,135.7,134.8,134.5,133.8,133.7,132.6,132.4,131.0,130.3,129.1,128.5,128.4,128.2,128.0,126.4,125.3,123.5,123.3,120.8,113.6,113.5,55.4,55.3,53.4,51.5,27.4,27.3,22.7.;HRMS(ESI)m/z calculated for C28H31BrNaO2=501.1399,found=501.1405。

实施例13

2,6-di-tert-butyl-4-(3-fluoro-1,3-bis(4-methoxyphenyl)allyl)phenol的合成

操作参考实施例1式(Ⅱ)收率为41%.1H NMR(500MHz,CDCl3)δ7.40(dd,J=22.2,8.7Hz,2H),7.28(d,J=4.3Hz,1H),{7.16(d,J=8.6Hz,1.5H),6.96(s,1.5H)},6.89(ddd,J=16.7,15.7,8.7Hz,2H),5.83(dd,J=21.2,11.1Hz,1H),5.11(s,1H),4.74(dd,J=11.1,2.8Hz,6H),3.84(d,J=15.6Hz,18H).;13C NMR(125MHz,CDCl3)δ160.2,158.0,152.2,136.8,135.8,135.8,135.0,132.9,129.3,129.3,129.0,128.8,124.5,124.4,113.8,113.8,113.7,113.7,110.8,110.6,55.3,55.2,47.0,46.9,34.4,30.3.;HRMS(ESI)m/z calculated for C31H37FNaO3=499.2619,found=499.2626。

实施例14

2,6-di-tert-butyl-4-(3-chloro-1,3-bis(4-methoxyphenyl)allyl)phenol合成。

操作参考实施例1式(Ⅱ)收率为67%.1H NMR(500MHz,CDCl3)δ7.32(d,J=8.7Hz,2H),7.08(d,J=8.6Hz,2H),6.93–6.81(m,6H),6.35(d,J=11.0Hz,1H),5.09(s,1H),4.63(d,J=11.0Hz,1H),3.83(s,3H),3.80(s,3H),1.39(s,18H).;13C NMR(125MHz,CDCl3)δ159.7,158.0,152.3,135.9,135.8,134.1,131.9,130.4,130.1,129.6,129.1,124.6,113.9,113.6,55.3,55.2,49.8,34.4,30.3.;HRMS(ESI)m/z calculated for C31H37ClNaO3=515.2323,found=515.2323。

实施例15

4-(1-(4-(benzyloxy)phenyl)-3-chloro-3-(4-methoxyphenyl)allyl)-2,6-di-tert-butylphenol的合成

操作参考实施例1式(Ⅱ)收率为53%.1H NMR(500MHz,CDCl3)1H NMR(500MHz,CDCl3)δ{7.54(d,J=8.9Hz,0.7H)7.23(dd,J=9.8,6.0Hz,1.3H)},7.48–7.27(m,6H),7.05(s,1H),6.94–6.73(m,6H),{6.46(d,J=9.6Hz,0.33H),6.37(d,J=11.0Hz,0.67H)},{5.27(d,J=9.6Hz,0.4H)4.64(d,J=11.0Hz,0.7H)},{5.11(s,0.36H),5.10(s,0.63H)},5.04(s,2H),{3.83(s,2H),3.82(s,1H)},{1.41(s,6H),1.39(s,12H)}.;13C NMR(125MHz,CDCl3)δ159.8,159.8,158.9,152.3,145.4,145.2,137.0,135.9,135.8,133.7,133.4,132.4,131.4,130.8,130.1,129.4,129.4,128.6,128.6,128.0,127.9,127.6,124.8,124.7,121.1,120.85,115.2,115.2,113.6,113.6,112.4,112.37,69.9,55.3,55.3,50.6,34.4,30.3,30.3.;HRMS(ESI)m/z calculated for C37H41ClNaO3=591.2636,found=591.1639。

实施例16

2,6-di-tert-butyl-4-(3-chloro-1-(3-methoxyphenyl)-3-(4-methoxyphenyl)allyl)phenol的合成

操作参考实施例1式(Ⅱ)收率为63%.1H NMR(500MHz,CDCl3)δ{7.61–7.44(m,1.5H),7.33(d,J=8.8Hz,0.5H)},7.28–7.19(m,1H),7.06(s,1H),6.94–6.66(m,6H),{6.48(d,J=9.6Hz,0.7H),6.39(d,J=11.0Hz,0.3H)},{5.28(d,J=9.6Hz,0.7H)4.65(d,J=11.0Hz,0.3H)},{5.11(s,0.7H),5.10(s,0.3H)},{3.84(s,1H),3.82(s,2H)},{3.79(s,2H),3.78(s,1H)},{1.41(s,12H),1.40(s,6H)}.;13C NMR(125MHz,CDCl3)δ159.8,159.6,152.4,145.2,135.9,135.8,133.3,132.4),130.9,130.1,129.4,129.3,128.6,127.9,124.8,124.6,120.8,120.6,114.4,114.2,113.6,113.6,111.4,111.4,55.3,55.2,50.7,34.4,30.3,30.3..;HRMS(ESI)m/z calculated for C31H37ClNaO3=515.2323,found=515.2335。

实施例17

2,6-di-tert-butyl-4-(3-chloro-1-(2-methoxyphenyl)-3-(4-methoxyphenyl)allyl)phenol的合成

操作参考实施例1式(Ⅱ)收率为53%.1H NMR(500MHz,CDCl3)1H NMR(500MHz,CDCl3)δ7.52–7.42(m,2H),7.20–7.10(m,2H),6.99(s,2H),6.91–6.73(m,4H),6.53(d,J=9.3Hz,1H),5.55(d,J=9.3Hz,1H),4.98(s,1H),3.76(s,3H),3.74(s,3H),1.33(s,18H).;13C NMR(125MHz,CDCl3)δ159.7,157.3,152.0,135.4,133.6,132.0,132.0,131.2,129.1,128.8,127.9,127.5,124.6,120.6,113.5,111.2,55.6,55.3,44.9,34.3,30.3.;HRMS(ESI)m/z calculated for C31H37ClNaO3=515.2323,found=515.2328。

实施例18

2,6-di-tert-butyl-4-(3-chloro-1-(6-methoxynaphthalen-2-yl)-3-(4-methoxyphenyl)allyl)phenol的合成

操作参考实施例1式(Ⅱ)收率为50%.1H NMR(500MHz,CDCl3)1H NMR(500MHz,CDCl3)δ{7.77–7.62(m,2.5H),7.62–7.45(m,1.5H)},{7.40–7.32(m,1.5H),7.23(dd,J=8.5,1.7Hz,0.5H)},7.19–7.11(m,2H),7.10(s,1H),6.93(s,1H),6.89(dd,J=8.8,1.1Hz,2H),{6.56(d,J=9.5Hz,0.5H),6.48(d,J=10.9Hz,0.5H)},{5.44(d,J=9.5Hz,0.5H)4.82(d,J=10.9Hz,0.5H)},{5.12(s,0.5H),5.11(s,0.5H)},{3.93(s,0.5H),3.92(s,0.5H)},{3.84(s,1.5H),3.83(s,1.5H)},{1.41(s,9H),1.39(s,9H)}.;13C NMR(125MHz,CDCl3)δ159.9,159.8,157.5,157.5,152.4,152.4,139.0,138.7,135.9,135.9,134.1,133.7,133.3,133.3,132.4,131.7,130.9,130.8,130.2,129.6,129.4,129.4,129.1,129.0,128.8,128.0,127.6,127.4,127.1,127.0,126.4,126.1,125.0,124.8,118.8,118.7,113.7,113.7,105.7,55.4,55.4,55.3,50.8,50.7,34.4,34.4,30.4,30.3.;HRMS(ESI)m/z calculated for C35H40ClO3=543.2660,found=543.2661。

实施例19

4-(1-(2-bromophenyl)-3-chloro-3-(4-methoxyphenyl)allyl)-2,6-di-tert-butylphenol的合成

操作参考实施例1式(Ⅱ)收率为32%.1H NMR(500MHz,CDCl3)δ7.58–7.43(m,1H),7.36–7.23(m,3H),7.13–7.01(m,2H),6.92(s,2H),6.91–6.76(m,2H),6.38(d,J=10.6Hz,1H),5.16(d,J=10.6Hz,1H),5.09(s,1H),3.83(s,3H),1.38(s,18H).;13C NMR(125MHz,CDCl3)δ159.8,152.3,143.2,135.8,133.2,132.8,132.0,130.3,130.1,129.7,129.3,127.9,127.7,124.7,124.6,113.6,55.3,49.5,34.4,30.3.;HRMS(ESI)m/z calculated for C30H34BrClNaO2=563.1322,found=563.1327。

实施例20

4-(1-(2-bromophenyl)-3-chloro-3-(Ferrocene)allyl)-2,6-di-tert-butylphenol的合成

操作参考实施例1式(Ⅱ)收率为50%.1H NMR(500MHz,CDCl3)δ7.17(d,J=8.6Hz,2H),7.01(s,2H),6.87(d,J=8.7Hz,2H),6.28(d,J=9.6Hz,1H),5.21(d,J=9.5Hz,1H),5.10(s,1H),4.55(s,2H),4.25(s,2H),4.17(s,5H),3.81(s,3H),1.42(s,18H).;13C NMR(125MHz,CDCl3)δ158.0,152.2,135.7,135.5,133.9,131.04,129.3,126.2,124.7,113.8,69.8,69.2,67.3,66.9,55.2,49.2,34.4,30.3.;HRMS(ESI)m/z calculated for C34H39ClNaFeO2=593.3188,found=593.3190。

实施例21

4-(3-chloro-3-(4-methoxyphenyl)-1-phenylallyl)-2,6-diisopropylphenol的合成

操作参考实施例1式(Ⅱ)收率为48%.1H NMR(500MHz,CDCl3)δ7.61–7.51(m,1H),7.41–7.14(m,6H),{6.96(s,1.3H)6.81(s,0.7H)},6.94–6.87(m,2H),6.51(d,J=9.5Hz,0.63H),6.42(d,J=10.9Hz,0.37H)},5.35(d,J=9.5Hz,1H),4.74(s,1H),{3.86(s,1H),3.85(s,2H)},3.26–3.09(m,2H),1.25(dd,J=10.5,4.5Hz,12H).;13C NMR(125MHz,CDCl3)δ159.9,159.8,148.6,148.6,143.9,143.6,135.2,134.8,133.8,133.7,132.5,131.5,130.8,130.8,130.1,129.5,128.6,128.5,128.4,128.2,128.0,128.0,126.4,126.3,123.4,123.3,113.6,55.3,55.3,50.5,27.4,27.3,22.7.;HRMS(ESI)m/z calculated for C28H31ClNaO2=457.1904,found=457.1910。

实施例22

2,6-di-tert-butyl-4-(3-iodo-1,3-bis(4-methoxyphenyl)allyl)phenol的合成

操作参考实施例1式(Ⅱ)收率为87%.1H NMR(500MHz,CDCl3)δ7.43(d,J=8.8Hz,1H),{7.26–7.23(m,1.2H),7.20(d,J=8.6Hz,0.8H)},7.09–7.01(m,2H),6.91–6.79(m,6H),{5.11(s,0.4H),5.10(s,0.6H)},{5.00(d,J=9.3Hz,0.4H),4.54(d,J=10.7Hz,0.6H)},3.83–3.78(m,6H),1.41(s,7H),1.39(s,11H).;13C NMR(125MHz,CDCl3)δ159.57(s),159.2 158.0,152.4,152.2,144.9,139.9,136.0,135.8,135.8,135.2,135.0,134.2,133.5,133.3,130.0,129.9,129.4,129.1,124.9,124.7,113.8,113.5,113.4,104.8,95.0,57.8,55.4,55.3,55.2,51.8,34.4,34.4,30.3,30.3.;HRMS(ESI)m/z calculated for C31H37INaO3=607.1680,found=607.1686。

实施例23

本发明在合成活性分子(3-bromo-1,3-bis(4-methoxyphenyl)allyl)-2,6-di-tert-Butylphenol中的应用

1)4-(3-bromo-1,3-bis(4-methoxyphenyl)allyl)-2,6-di-tert-butylphenyl tert-butyl carbonate(4)的合成

在室温下,将二碳酸二叔丁酯(0.15mmol,1.5equiv)滴加到3aa(0.1mmol,1.0equiv)和DMAP(0.005mmol,50mol%)的THF(2mL)中的溶液中。室温搅拌通过TLC分析直至反应完成。将混合物真空浓缩,并通过硅胶快速色谱法纯化,得到4-(3-bromo-1,3-bis(4-methoxyphenyl)allyl)-2,6-di-tert-butylphenyl tert-butyl carbonate(7aa),为白色固体收率96%.1H NMR(500MHz,CDCl3)δ7.32–7.27(m,2H),7.05(d,J=8.4Hz,2H),7.03–6.96(m,2H),6.93–6.80(m,4H),6.56(d,J=10.9Hz,1H),4.61(d,J=10.9Hz,1H),3.83(s,3H),3.80(s,3H),1.53(s,9H),1.31(d,J=3.8Hz,18H).;13C NMR(125MHz,CDCl3)δ159.7,158.2,152.9,146.8,142.6,139.6,135.7,134.9,130.9,130.2,129.2,126.0,120.8,113.9,113.6,55.3,55.2,50.8,35.5,31.4,27.8.;HRMS(ESI)m/z calculated for C36H45NaBrO5=659.2342,found=659.2347。

2)2,6-di-tert-butyl-4-(1,3,5-tris(4-methoxyphenyl)pent-2-en-4-yn-1-yl)phenol的合成

向加入搅拌子的反应管中加入3aa(0.1mmol),Pd(PPh3)2Cl2(4mol%),CuI(2mol%)。用氮气置换空气,加入1mL THF,3.0当量Et3N。将4-乙炔基苯甲醚(1.5equiv)溶解在1mL THF中并加入到反应管中。在室温下搅拌直至3完全耗尽。将混合物真空浓缩,通过硅胶快速色谱纯化,得到2,6-di-tert-butyl-4-(1,3,5-tris(4-methoxyphenyl)pent-2-en-4-yn-1-yl)phenol(8aa),为浅黄色油状物,产率为64%。1H NMR(500MHz,CDCl3)δ7.49–7.43(m,3H),7.32–7.27(m,1H),7.07(d,J=8.6Hz,2H),6.90–6.82(m,8H),6.59(d,J=10.9Hz,1H),5.09(s,1H),4.57(d,J=10.9Hz,1H),3.83(d,J=1.2Hz,6H),3.80(s,3H),1.39(s,18H).;13C NMR(125MHz,CDCl3)δ160.2,159.6,158.1,152.3,136.2,135.8,135.5,134.0,133.8,131.0,130.3,129.3,129.1,124.6,120.3,114.1,113.9,113.6,81.2,72.9,55.3,55.3,55.2,50.8,34.4,30.3.;HRMS(ESI)m/z calculated for C40H44NaO4=611.3132,found=611.3240。

实施例39

Methyl 2-(4-hydroxyphenyl)-2-phenylacetate的克级制备

操作参考实施例1式(Ⅰ)收率为66%。

再多了解一些
当前第1页1 2 3 
网友询问留言 已有0条留言
  • 还没有人留言评论。精彩留言会获得点赞!
1