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CN112300085A - 一种甲基杂环化合物的烯基化方法 - Google Patents

一种甲基杂环化合物的烯基化方法 Download PDF

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CN112300085A
CN112300085A CN202011282259.1A CN202011282259A CN112300085A CN 112300085 A CN112300085 A CN 112300085A CN 202011282259 A CN202011282259 A CN 202011282259A CN 112300085 A CN112300085 A CN 112300085A
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heterocyclic compound
alkenylation
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徐清
韩峰
李双艳
陈建辉
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Wenzhou University
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    • C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
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Abstract

本发明公开了一种甲基杂环化合物的烯基化方法，甲基杂环化合物与醇在无需过渡金属催化剂参与条件下，甲基进行烯基化反应合成烯基杂环化合物的绿色方法。该方法使用廉价易得、来源广泛、稳定低毒的醇类为烯基化试剂，无需任何过渡金属催化剂及配体，在普通水溶性无机碱作用下，可直接利用空气为方便、温和、高效的氧化剂，与甲基杂环化合物通过氧化缩合等过程进行C‑烯基化反应直接合成烯基杂环化合物。该反应条件简单、无需惰性气体保护、对设备要求低、易于操作，副产物为水，水溶性无机碱易去除，产物无金属残留、易于纯化，适用于喹啉、喹喔啉、吡啶、苯并噻唑等杂环体系，具有较广的适用范围，因此，具有一定的研究意义和潜在的应用前景。

Description

一种甲基杂环化合物的烯基化方法
技术领域
本发明涉及化学合成技术领域，具体涉及一种甲基杂环化合物的烯基化方法。
背景技术
喹喔啉等杂环结构大量存在于天然产物、农药和生物药理活性化合物中，含喹喔啉等杂环结构的化合物也是重要的精细化工和药物合成中间体。在杂环上导入烯基结构是对杂环进行改良改性的重要手段，其中可通过甲基杂环化合物的烯基化反应制备烯基杂环化合物、然后再通过烯基结构的官能团化反应导入所需要的各种官能团。最常用的甲基杂环化合物的烯基化方法是醛与杂环甲基化合物的缩合反应来，但醛类化合物活性高、不稳定、臭味重、毒性较高，且反应需要强碱条件、脱水试剂或其他缩合试剂，产生很多废弃物。
近几年有文献报道，在过渡金属络合物催化下、醇可作为烯基化试剂实现甲基杂环化合物的烯基化反应合成烯基杂环化合物。但这些方法需使用价格昂贵、制备繁琐、且对空气敏感、配体络合才能稳定的过渡金属络合物，并且反应需在惰性条件下进行，还存在过渡金属在产物中残留的问题，也有许多待改进之处。
因此，寻找更好的新方法实现甲基杂环化合物的C-烯基化反应合成烯基杂环化合物对有机合成、生化和药物化学家而言都是非常有意义的研究。
发明内容
针对现有技术存在的不足，本发明的目的在于提供一种甲基杂环化合物的烯基化方法，该方法使用廉价易得、来源广泛、稳定低毒的醇类为烯基化试剂，不使用过渡金属催化剂及配体，以空气为氧化剂、在水溶性无机碱作用下，实现甲基杂环化合物与醇的经过氧化缩合等过程的C-烯基化反应制备烯基杂环化合物的绿色合成方法，副产物为水，高效无污染。
为实现上述目的，本发明提供了如下技术方案：一种甲基杂环化合物的烯基化方法，醇与甲基杂环化合物在碱作用下直接利用空气为氧化剂，在甲基位进行C-烯基化反应得到烯基杂环化合物，反应温度为100～180℃，反应时间为6～60小时，副产物为水，反应式为：
Figure BDA0002781169950000021
其中：
R1是在2-、3-或4-位官能团取代的苯基或是取代芳基或是取代杂芳基或是脂肪烷基或是取代烷基；
R2是氢或是烷基或是取代烷基或是吸电子或是缺电子取代基，或是与杂环相连的无取代或取代苯并结构，或是含N、O、S等元素杂环结构。
作为优选的，反应无需过渡金属催化剂及配体。
作为优选的，反应在水溶性无机碱作用下进行，水溶性无机碱为Cs2CO3、K2CO3、Na2CO3、Li2CO3、KHCO3、NaHCO3、CH3COOK、K3PO4 .3H2O、LiOH、NaOH、KOH、CsOH、t-BuONa或t-BuOK。
作为优选的，所述水溶性无机碱优化为KOH或CsOH，水溶性无机碱的用量为10～200mol％。
作为优选的，水溶性无机碱的用量采用40-100mol％。
作为优选的，反应采用有机溶剂，有机溶剂为甲苯或二甲苯。
作为优选的，反应在氧气或空气环境下进行，反应进行的温度为120-160℃，反应时间为12-48小时。
作为优选的，反应在空气和水溶性无机碱作用下进行。
作为优选的，反应温度为100-140℃，反应时间为18-36小时。
本发明的优点是：与现有技术相比，本发明所使用的醇、碱和甲基杂环化合物普遍商品化，可以直接购买得到。由于可使用廉价易得、来源广泛、稳定低毒、相对绿色的醇类化合物为烯基化试剂，不使用任何过渡金属催化剂和配体，反应无需惰性气体保护，利用空气为氧化剂在空气下直接进行，易于操作，副产物为水，绿色环保无污染，因此本方法对反应条件的要求较低、适用范围较广，与已知方法相比优势明显。
具体实施方式
通过下述实施方式将有助于理解本发明，但并不限制于本发明的内容。
本发明公开了一种甲基杂环化合物的烯基化方法，醇与甲基杂环化合物在碱作用下直接利用空气为氧化剂，在甲基位进行C-烯基化反应得到烯基杂环化合物，反应温度为100～180℃，反应时间为6～60小时，副产物为水，反应式为：
Figure BDA0002781169950000031
其中：
R1是在2-、3-或4-位官能团取代的苯基或是取代芳基或是取代杂芳基或是脂肪烷基或是取代烷基；作为优选的，R1可以是在2-、3-、或4-位各种官能团取代的苯基或各类取代芳基、取代噻吩、取代吡啶等取代杂芳基，也可以是脂肪烷基或取代烷基。
R2是氢或是烷基或是取代烷基或是吸电子或是缺电子取代基。作为优选的，R2可以是氢(H)，也可以是甲基、乙基等烷基和取代烷基，可以是卤素、三氟甲基、烷氧基等各种吸电子或缺电子取代基，还可以是与杂环相连的无取代或取代苯并结构，或是含N、O、S等元素杂环结构。。
下面结合具体实施例对本发明作进一步说明：
实施例1
2-甲基喹喔啉和苯甲醇反应制备(E)-2-苯乙烯基喹喔啉
Figure BDA0002781169950000041
100mL反应管中依次加入2-甲基喹喔啉(0.5mmol)，苯甲醇(1.5mmol,3equiv.),KOH(60mol％),1mL甲苯，直接在空气下密封加热到120℃反应18h。产物用柱色谱分离提纯，分离收率87％。1H NMR(500MHz,CDCl3):δ9.05(s,1H),8.07(d,J＝7.5Hz,2H),7.88(d,J＝16.5Hz,1H),7.78-7.74(m,1H),7.72-7.69(m,1H),7.66(d,J＝7.5Hz,2H),7.44-7.40(m,3H),7.38-7.36(m,1H).13C NMR(125.4MHz,CDCl3):δ150.7,144.4,142.5,141.6,136.5,136.1,130.3,129.3,129.23,129.20,129.18,128.9,127.5,125.4。
实施例2
2-甲基喹喔啉和4-甲基苯甲醇反应制备(E)-2-(4-甲基苯乙烯)基喹喔啉
Figure BDA0002781169950000042
100mL反应管中依次加入2-甲基喹喔啉(0.5mmol)，4-甲基苯甲醇(1.5mmol,3equiv.),KOH(60mol％),1mL甲苯，直接在空气下密封加热到120℃反应18h。产物用柱色谱分离提纯，分离收率60％。1H NMR(500MHz,CDCl3):δ9.04(s,1H),8.07-8.05(m,2H),7.85(d,J＝16.5Hz,1H),7.77-7.74(m,1H),7.71-7.68(m,1H),7.56(d,J＝8.0Hz,2H),7.34(d,J＝16.5Hz,1H),7.26-7.23(m,2H),2.40(s,3H).13C NMR(125.4MHz,CDCl3):δ150.7,144.5,142.5,141.5,139.5,136.5,133.3,130.3,129.7(2C),129.2,127.5(2C),124.4,21.4。
实施例3
2-甲基喹喔啉和3-甲基苯甲醇反应制备(E)-2-(3-甲基苯乙烯)基喹喔啉
Figure BDA0002781169950000051
100mL反应管中依次加入2-甲基喹喔啉(0.5mmol)，3-甲基苯甲醇(1.5mmol,3equiv.),KOH(60mol％),1mL甲苯，直接在空气下密封加热到120℃反应18h。产物用柱色谱分离提纯，分离收率64％。1H NMR(500MHz,CDCl3)δ9.04(s,1H),8.07(d,J＝8.4Hz,2H),7.84(d,J＝16.3Hz,1H),7.77–7.72(m,1H),7.72–7.67(m,1H),7.46(d,J＝11.6Hz,2H),7.37(d,J＝16.3Hz,1H),7.30(t,J＝7.6Hz,1H),7.17(d,J＝7.5Hz,1H),2.40(s,3H).13C NMR(125.4MHz,CDCl3)δ150.6,144.4,142.3,141.5,138.5,136.8,135.9,130.4,130.2,129.3,129.1,129.0,128.8,128.2,125.0,124.7,21.4.HRMS Calcd for[C17H14N2+H]+:247.1230；found:247.1221。
实施例4
2-甲基喹喔啉和2-甲基苯甲醇反应制备(E)-2-(2-甲基苯乙烯)基喹喔啉
Figure BDA0002781169950000061
100mL反应管中依次加入2-甲基喹喔啉(0.5mmol)，2-甲基苯甲醇(1.5mmol,3equiv.),KOH(60mol％),1mL甲苯，直接在空气下密封加热到120℃反应18h。产物用柱色谱分离提纯，分离收率73％。1H NMR(500MHz,CDCl3)δ9.04(s,1H),8.15(d,J＝16.1Hz,1H),8.09(t,J＝8.8Hz,2H),7.79–7.67(m,3H),7.31(d,J＝16.2Hz,1H),7.28–7.21(m,3H),2.54(s,3H).13C NMR(125.4MHz,CDCl3)δ150.7,144.5,142.2,141.6,137.1,135.0,134.4,130.8,130.4,129.3,129.1,129.1,126.4,126.2,125.9,20.0.HRMS Calcd for[C17H14N2+H]+:247.1230；found:247.1221。
实施例5
2-甲基喹喔啉和4-叔丁基苯甲醇反应制备(E)-2-(4-叔丁基苯乙烯)基喹喔啉
Figure BDA0002781169950000062
100mL反应管中依次加入2-甲基喹喔啉(0.5mmol)，4-叔丁基苯甲醇(1.5mmol,3equiv.),KOH(60mol％),1mL甲苯，直接在空气下密封加热到120℃反应18h。产物用柱色谱分离提纯，分离收率75％。1H NMR(500MHz,CDCl3)δ9.05(s,1H),8.07(d,J＝12.0Hz,2H),7.86(d,J＝16.3Hz,1H),7.74(t,J＝8.3Hz,1H),7.72–7.65(m,1H),7.60(d,J＝8.4Hz,2H),7.45(d,J＝8.4Hz,2H),7.36(d,J＝16.3Hz,1H),1.35(s,9H).13C NMR(125.4MHz,CDCl3)δ152.8,150.7,144.4,142.2,141.5,136.5,133.2,130.4,129.2,129.1,129.0,127.3,125.9,124.39,34.9,31.2.HRMS Calcd for[C20H20N2+H]+:289.1699；found:289.1694。
实施例6
2-甲基喹喔啉和2-甲基苯甲醇反应制备(E)-2-(4-甲氧基苯乙烯)基喹喔啉
Figure BDA0002781169950000071
100mL反应管中依次加入2-甲基喹喔啉(0.5mmol)，4-甲氧基苯甲醇(1.5mmol,3equiv.),KOH(60mol％),1mL甲苯，直接在空气下密封加热到120℃反应18h。产物用柱色谱分离提纯，分离收率69％。1H NMR(500MHz,CDCl3):δ9.02(s,1H),8.06(t,J＝7.3Hz,2H),7.83(d,J＝16.0Hz,1H),7.75(t,J＝7.5Hz,1H),7.69(t,J＝7.5Hz,1H),7.61(d,J＝8.0Hz,2H),7.25(d,J＝16.0Hz,1H),6.96(d,J＝8.0Hz,2H),3.86(s,3H).13C NMR(125.4MHz,CDCl3):δ160.6,151.0,144.4,142.5,141.4,136.1,130.3,129.13,129.05,128.99,128.96,128.8,123.1,114.4,55.4。
实施例7
2-甲基喹喔啉和3-甲基苯甲醇反应制备(E)-2-(3-甲氧基苯乙烯)基喹喔啉
Figure BDA0002781169950000072
100mL反应管中依次加入2-甲基喹喔啉(0.5mmol)，3-甲氧基苯甲醇(1.5mmol,3equiv.),KOH(60mol％),1mL甲苯，直接在空气下密封加热到120℃反应18h。产物用柱色谱分离提纯，分离收率66％。1H NMR(500MHz,CDCl3):δ9.05(s,1H),8.07(t,J＝6.5Hz,2H),7.84(d,J＝16.0Hz,1H),7.76(t,J＝7.8Hz,1H),7.71(t,J＝7.5Hz,1H),7.39-7.32(m,2H),7.26(d,J＝8.0Hz,1H),7.19(s,1H),6.93(d,J＝8.0Hz,1H),3.87(s,3H).13C NMR(125.4MHz,CDCl3):δ160.0,150.6,144.4,142.5,141.6,137.4,136.3,130.3,129.9,129.3,129.2(2C),125.7,120.3,115.3,112.3,55.3。
实施例8
2-甲基喹喔啉和3-甲基苯甲醇反应制备(E)-2-(2-甲氧基苯乙烯)基喹喔啉
Figure BDA0002781169950000081
100mL反应管中依次加入2-甲基喹喔啉(0.5mmol)，2-甲氧基苯甲醇(1.5mmol,3equiv.),KOH(60mol％),1mL甲苯，直接在空气下密封加热到120℃反应18h。产物用柱色谱分离提纯，分离收率75％。1H NMR(500MHz,CDCl3)δ9.09(s,1H),8.19(d,J＝16.5Hz,1H),8.11–8.03(m,2H),7.73(t,J＝6.9Hz,1H),7.71–7.65(m,2H),7.45(d,J＝16.5Hz,1H),7.33(t,J＝7.8Hz,1H),7.01(t,J＝7.5Hz,1H),6.94(d,J＝8.3Hz,1H),3.93(s,3H).13C NMR(125.4MHz,CDCl3)δ157.8,151.2,144.4,142.3,141.4,131.8,130.5,130.2,129.1,129.1,127.7,125.9,125.0,120.9,111.1,55.6。
实施例9
2-甲基喹喔啉和3,4-亚甲二氧基苯甲醇反应制备(E)-2-(3,4-亚甲二氧基苯乙烯)基喹喔啉
Figure BDA0002781169950000082
100mL反应管中依次加入2-甲基喹喔啉(0.5mmol)，2-萘甲醇(1.5mmol,3equiv.),KOH(60mol％),1mL甲苯，直接在空气下密封加热到120℃反应18h。产物用柱色谱分离提纯，分离收率67％。1H NMR(500MHz,CDCl3)δ9.06(s,1H),8.14(d,J＝8.1Hz,1H),8.09(d,J＝8.2Hz,1H),7.86(d,J＝16.2Hz,1H),7.78(t,J＝7.5Hz,1H),7.75–7.68(m,1H),7.31–7.19(m,3H),7.14(d,J＝8.0Hz,1H),6.87(d,J＝8.0Hz,1H),6.03(s,2H).13C NMR(125.4MHz,CDCl3)δ150.8,148.8,148.4,144.4,142.5,141.5,136.1,130.6,130.2,129.1,129.1,129.0,123.5,123.3,108.6,106.1,101.4.HRMS Calcd for[C17H12N2O2+H]+:277.0972；found:277.0974。
实施例10
2-甲基喹喔啉和4-氟苯甲醇反应制备(E)-2-(4-氟苯乙烯)基喹喔啉
Figure BDA0002781169950000091
100mL反应管中依次加入2-甲基喹喔啉(0.5mmol)，4-氟苯甲醇(1.5mmol,3equiv.),KOH(60mol％),1mL甲苯，直接在空气下密封加热到120℃反应18h。产物用柱色谱分离提纯，分离收率72％。1H NMR(500MHz,CDCl3)δ9.03(s,1H),8.09(d,J＝10.7Hz,2H),7.84(d,J＝16.3Hz,1H),7.78(t,J＝7.5Hz,1H),7.73(t,J＝8.1Hz,1H),7.42(d,J＝7.7Hz,1H),7.41–7.33(m,3H),7.06(t,J＝8.1Hz,1H).13C NMR(125.4MHz,CDCl3)δ164.1,162.2,150.0,144.4,142.2,141.6,138.2(d,J＝7.7Hz),135.3,130.6,130.4(d,J＝8.3Hz),129.6,129.1(d,J＝11.1Hz),126.3,123.4,116.1(d,J＝21.5Hz),113.8(d,J＝22.0Hz).HRMS Calcd for[C20H20FN2+H]+:252.1057；found:252.1058。
实施例11
2-甲基喹喔啉和4-氯苯甲醇反应制备(E)-2-(4-氯苯乙烯)基喹喔啉
Figure BDA0002781169950000101
100mL反应管中依次加入2-甲基喹喔啉(0.5mmol)，4-氟苯甲醇(1.5mmol,3equiv.),KOH(60mol％),1mL甲苯，直接在空气下密封加热到120℃反应18h。产物用柱色谱分离提纯，分离收率71％。1H NMR(500MHz,CDCl3)δ9.04(s,1H),8.09(d,J＝7.8Hz,2H),7.83(d,J＝16.3Hz,1H),7.80-7.72(m,2H),7.65(s,1H),7.53(d,J＝6.9Hz,1H),7.39(d,J＝19.3Hz,1H),7.34(t,J＝8.3Hz,2H).13C NMR(125.4MHz,CDCl3)δ149.9,144.4,142.1,141.7,137.8,135.1,134.9,130.1,129.7,129.2,129.,127.3,126.3,125.7.HRMS Calcdfor[C20H20ClN2+H]+:268.0762；found:268.0762。
实施例12
2-甲基喹喔啉和4-溴苯甲醇反应制备(E)-2-(4-溴苯乙烯)基喹喔啉
Figure BDA0002781169950000102
100mL反应管中依次加入2-甲基喹喔啉(0.5mmol)，4-溴苯甲醇(1.5mmol,3equiv.),KOH(60mol％),1mL甲苯，直接在空气下密封加热到120℃反应18h。产物用柱色谱分离提纯，分离收率51％。1H NMR(500MHz,CDCl3)δ9.05(s,1H),8.11(t,J＝8.7Hz,2H),7.86–7.69(m,4H),7.58(d,J＝7.5Hz,1H),7.49(d,J＝7.7Hz,1H),7.41(d,J＝16.2Hz,1H),7.30(t,J＝7.8Hz,1H).13C NMR(125.4MHz,CDCl3)δ150.1,144.4,142.5,141.8,138.2,134.7,131.9,130.4,130.4,130.2,129.5,129.3,129.2,126.6,126.0,123.1。
实施例13
2-甲基喹喔啉和4-三氟甲基苯甲醇反应制备(E)-2-(4-三氟甲基苯乙烯)基喹喔啉
Figure BDA0002781169950000111
100mL反应管中依次加入2-甲基喹喔啉(0.5mmol)，4-三氟甲基苯甲醇(1.5mmol,3equiv.),KOH(100mol％),1mL甲苯，直接在空气下密封加热到120℃反应18h。产物用柱色谱分离提纯，分离收率80％。1H NMR(400MHz,CDCl3)δ9.07(s,1H),8.12(d,J＝7.5Hz,2H),7.91(dd,J＝16.3,2.6Hz,1H),7.82-7.76(m,4H),7.70(d,J＝7.5Hz,2H),7.47(dd,J＝16.3,2.8Hz,1H).13C NMR(125.4MHz,CDCl3)δ149.8,144.4,142.4,141.8,139.3,134.6,130.8,130.6,130.5,129.7,129.2,129.2,127.5,125.8(q,J＝3.7Hz),125.1,122.9。
实施例14
2-甲基喹喔啉和1-萘甲醇反应制备(E)-2-(1-萘乙烯)基喹喔啉
Figure BDA0002781169950000112
100mL反应管中依次加入2-甲基喹喔啉(0.5mmol)，1-萘甲醇(1.5mmol,3equiv.),KOH(60mol％),1mL甲苯，直接在空气下密封加热到120℃反应18h。产物用柱色谱分离提纯，分离收率83％。1H NMR(500MHz,CDCl3)δ9.08(s,1H),8.71(d,J＝16.0Hz,1H),8.33(d,J＝8.4Hz,1H),8.10(t,J＝9.2Hz,2H),7.89(dd,J＝12.5,6.7Hz,3H),7.77(t,J＝8.3Hz,1H),7.72(t,J＝8.3Hz,1H),7.60(t,J＝6.5Hz,1H),7.55-7.51(m,2H),7.43(d,J＝15.9Hz,1H).13C NMR(125.4MHz,CDCl3)δ150.6,144.7,142.5,141.7,133.8,133.5,133.4,131.5,130.3,129.6,129.3,129.3,129.2,128.8,127.9,126.6,126.1,125.6,124.4,123.6。
实施例15
2-甲基喹喔啉和2-萘甲醇反应制备(E)-2-(2-萘乙烯)基喹喔啉
Figure BDA0002781169950000121
100mL反应管中依次加入2-甲基喹喔啉(0.5mmol)，2-萘甲醇(1.5mmol,3equiv.),KOH(60mol％),1mL甲苯，直接在空气下密封加热到120℃反应18h。产物用柱色谱分离提纯，分离收率73％。1H NMR(500MHz,CDCl3)δ9.08(s,1H),8.08(d,J＝9.4Hz,2H),8.06–8.01(m,2H),7.90–7.82(m,4H),7.79–7.75(m,1H),7.71(t,J＝8.3Hz,1H),7.56–7.45(m,3H).13CNMR(125.4MHz,CDCl3)δ150.7,144.5,142.5,141.6,136.5,133.8,133.5,133.5,130.3,129.3,129.2,129.2,128.8,128.7,128.4,127.8,126.8,126.6,125.5,123.4.HRMS Calcdfor[C20H14N2+H]+:283.1230；found:283.1229。
实施例16
2-甲基喹喔啉和2-吡啶甲醇反应制备(E)-2-(2-吡啶乙烯)基喹喔啉
Figure BDA0002781169950000122
100mL反应管中依次加入2-甲基喹喔啉(0.5mmol)，2-吡啶甲醇(1.5mmol,3equiv.),KOH(60mol％),1mL甲苯，直接在空气下密封加热到100℃反应36h。产物用柱色谱分离提纯，分离收率55％。1H NMR(500MHz,CDCl3)δ9.06(s,1H),8.69(d,J＝4.6Hz,1H),8.09(dd,J＝8.8,2.8Hz,2H),8.01–7.87(m,2H),7.83–7.68(m,3H),7.54(d,J＝7.8Hz,1H),7.36–7.17(m,1H).13C NMR(125.4MHz,CDCl3)δ154.3,150.1,150.0,145.1,142.5,141.9,136.8,135.3,130.3,129.6,129.4,129.2,128.9,123.5,123.3.HRMS Calcd for[C15H11N3+H]+:234.1026；found:234.1019。
实施例17
2-甲基喹喔啉和3-吡啶甲醇反应制备(E)-2-(3-吡啶乙烯)基喹喔啉
Figure BDA0002781169950000131
100mL反应管中依次加入2-甲基喹喔啉(0.5mmol)，3-吡啶甲醇(1.5mmol,3equiv.),KOH(100mol％),1mL甲苯，直接在空气下密封加热到120℃反应36h。产物用柱色谱分离提纯，分离收率％。1H NMR(500MHz,CDCl3)δ9.04(s,1H),8.88(d,J＝2.0Hz,1H),8.59(dd,J＝4.8,1.5Hz,1H),8.18–8.05(m,2H),7.97(d,J＝3.5Hz,1H),7.88(d,J＝16.3Hz,1H),7.83–7.69(m,2H),7.44(d,J＝16.3Hz,1H),7.37(dd,J＝7.9,4.8Hz,1H).13C NMR(125.4MHz,CDCl3)δ149.7,149.7,149.2,144.4,142.4,141.8,133.5,132.4,131.8,130.5,129.6,129.2,129.17,127.2,123.8.HRMS Calcd for[C15H11N3+H]+:234.1026；found:234.1019。
实施例18
2-甲基喹喔啉和噻吩-2-甲醇反应制备(E)-2-(2-噻吩乙烯)基喹喔啉
Figure BDA0002781169950000141
100mL反应管中依次加入2-甲基喹喔啉(0.5mmol)，噻吩-2-甲醇(1.5mmol,3equiv.),KOH(60mol％),1mL甲苯，直接在空气下密封加热到120℃反应24h。产物用柱色谱分离提纯，分离收率71％。1H NMR(500MHz,CDCl3)δ8.94(s,1H),8.10–7.95(m,3H),7.78–7.72(m,1H),7.68(t,J＝7.6Hz,1H),7.34(d,J＝5.0Hz,1H),7.28(d,J＝3.5Hz,1H),7.16(d,J＝15.9Hz,1H),7.07(dd,J＝5.0,3.7Hz,1H).13C NMR(125.4MHz,CDCl3)δ150.2,144.5,142.3,141.6,141.5,130.4,129.4,129.2,129.2,129.1,129.0,128.1,127.0,124.1.HRMSCalcd for[C15H11N2S+H]+:239.0637；found:239.0636。
实施例19
2-甲基喹啉和苯甲醇反应制备(E)-2-(2-苯乙烯)基喹啉
Figure BDA0002781169950000142
100mL反应管中依次加入2-甲基喹啉(2mmol)，苯甲醇(4mmol,2equiv.),CsOH(40mol％),1.5mL二甲苯，直接在空气下密封加热到140℃反应12h。产物用柱色谱分离提纯，分离收率88％。1H NMR(500MHz,CDCl3):δ8.12(d,J＝8.5Hz,1H),8.08(d,J＝8.5Hz,1H),7.80(d,J＝8.0Hz,1H),7.72-7.63(m,5H),7.49(t,J＝7.0Hz,1H),7.43-7.39(m,3H),7.32(t,J＝7.5Hz,1H).13C NMR(125.4MHz,CDCl3):δ156.0,148.3,136.6,136.3,134.5,129.7,129.3,129.1,128.8,128.6,127.5,127.4,127.3,126.2,119.3。
实施例20
2-甲基喹啉和2-甲氧基苯甲醇反应制备(E)-2-(2-甲氧基苯乙烯)基喹啉
Figure BDA0002781169950000151
100mL反应管中依次加入2-甲基喹啉(2mmol)，2-甲氧基苯甲醇(4mmol,2equiv.),CsOH(40mol％),1.5mL二甲苯，直接在空气下密封加热到140℃反应12h。产物用柱色谱分离提纯，分离收率74％。1H NMR(300MHz,CDCl3):δ8.14-8.01(m,3H),7.80-7.69(m,4H),7.53-7.45(m,2H),7.35-7.28(m,1H),7.05-6.94(m,2H),3.95(s,3H).13C NMR(125.4MHz,CDCl3):δ157.5,156.8,148.3,136.2,129.8,129.6(2C),129.4,129.2,127.5,127.3,127.2,126.0,125.6,120.9,119.0,111.0,55.6。
实施例21
2-甲基苯并噻唑和苯甲醇反应制备(E)-2-(2-苯乙烯)基苯并噻唑
Figure BDA0002781169950000152
100mL反应管中依次加入2-甲基苯并噻唑(0.5mmol)，苯甲醇(1.5mmol,3equiv.),KOH(60mol％),1mL甲苯，直接在空气下密封加热到120℃反应18h。产物用柱色谱分离提纯，分离收率82％。1H NMR(500MHz,CDCl3)δ9.03(s,1H),8.07(d,J＝8.4Hz,2H),7.86(d,J＝16.3Hz,1H),7.75(t,J＝8.3Hz,1H),7.72–7.67(m,1H),7.65(d,J＝8.6Hz,2H),7.42(d,J＝7.1Hz,1H),7.40(d,J＝1.6Hz,1H),7.38–7.33(m,1H).13C NMR(125.4MHz,CDCl3)δ150.5,144.4,142.3,141.6.136.6,136.0,130.4,129.3,129.2,129.1,128.9,127.5,125.2。
实施例22
2-甲基嘧啶和苯甲醇反应制备(E)-2-(2-苯乙烯)基嘧啶
Figure BDA0002781169950000161
100mL反应管中依次加入2-甲基嘧啶(0.5mmol)，苯甲醇(1.5mmol,3equiv.),KOH(60mol％),1mL甲苯，直接在空气下密封加热到120℃反应18h。产物用柱色谱分离提纯，分离收率87％。(E)-4-styrylpyrimidine(4v).1H NMR(500MHz,CDCl3)δ9.17(s,1H),8.67(s,1H),7.90(d,J＝16.0Hz,1H),7.60(d,J＝7.1Hz,2H),7.42-7.32(m,4H),7.05(d,J＝18.5Hz,1H).13C NMR(125.4MHz,CDCl3)δ162.4,158.6,157.1,137.8,135.5,129.6,127.7,125.4,118.7。
实施例23
2-甲基吡嗪和苯甲醇反应制备(E)-2-(2-苯乙烯)基吡嗪
Figure BDA0002781169950000162
100mL反应管中依次加入2-甲基吡嗪(0.5mmol)，苯甲醇(1.5mmol,3equiv.),KOH(100mol％),1mL甲苯，直接在空气下密封加热到120℃反应24h。产物用柱色谱分离提纯，分离收率65％。1H NMR(400MHz,CDCl3)δ8.69(s,1H),8.58(s,1H),8.45(s,1H),7.79(d,J＝16.1Hz,1H),7.63(d,J＝7.1Hz,2H),7.43(t,J＝7.3Hz,2H),7.38(d,J＝7.2Hz,1H),7.20(d,J＝16.1Hz,1H).13C NMR(125.4MHz,CDCl3)δ151.3,144.3,143.7,142.7,136.0,135.3,129.0,128.8,127.3,124.0。
上述实施例对本发明的具体描述，只用于对本发明进行进一步说明，不能理解为对本发明保护范围的限定，本领域的技术工程师根据上述发明的内容对本发明作出一些非本质的改进和调整均落入本发明的保护范围之内。

Claims (9)

1.一种甲基杂环化合物的烯基化方法，其特征在于：醇与甲基杂环化合物在碱作用下直接利用空气为氧化剂，在甲基位进行C-烯基化反应得到烯基杂环化合物，反应温度为100～180℃，反应时间为6～60小时，副产物为水，反应式为：
Figure FDA0002781169940000011
其中：
R1是在2-、3-或4-位官能团取代的苯基或是取代芳基或是取代杂芳基或是脂肪烷基或是取代烷基；
R2是氢或是烷基或是取代烷基或是吸电子或是缺电子取代基，或是与杂环相连的无取代或取代苯并结构，或是含N、O、S等元素杂环结构。
2.根据权利要求1所述的一种甲基杂环化合物的烯基化方法，其特征在于：反应无需过渡金属催化剂及配体。
3.根据权利要求1所述的一种甲基杂环化合物的烯基化方法，其特征在于：反应在水溶性无机碱作用下进行，水溶性无机碱为Cs2CO3、K2CO3、Na2CO3、Li2CO3、KHCO3、NaHCO3、CH3COOK、K3PO4 .3H2O、LiOH、NaOH、KOH、CsOH、t-BuONa或t-BuOK。
4.根据权利要求3所述的一种甲基杂环化合物的烯基化方法，其特征在于：所述水溶性无机碱优化为KOH或CsOH，水溶性无机碱的用量为10～200mol％。
5.根据权利要求4所述的一种甲基杂环化合物的烯基化方法，其特征在于：水溶性无机碱的用量采用40-100mol％。
6.根据权利要求1所述的一种甲基杂环化合物的烯基化方法，其特征在于：反应采用有机溶剂，有机溶剂为甲苯或二甲苯。
7.根据权利要求1所述的一种甲基杂环化合物的烯基化方法，其特征在于：反应在氧气或空气环境下进行，反应进行的温度为120-160℃，反应时间为12-48小时。
8.根据权利要求1所述的一种甲基杂环化合物的烯基化方法，其特征在于：反应在空气和水溶性无机碱作用下进行。
9.根据权利要求1所述的一种甲基杂环化合物的烯基化方法，其特征在于：反应温度为100-140℃，反应时间为18-36小时。
CN202011282259.1A 2020-11-17 2020-11-17 一种甲基杂环化合物的烯基化方法 Pending CN112300085A (zh)

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