CN111620839B - 一种金属催化下的串联合成苯基吡咯烷衍生物的制备方法 - Google Patents

一种金属催化下的串联合成苯基吡咯烷衍生物的制备方法 Download PDF

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CN111620839B
CN111620839B CN202010610637.8A CN202010610637A CN111620839B CN 111620839 B CN111620839 B CN 111620839B CN 202010610637 A CN202010610637 A CN 202010610637A CN 111620839 B CN111620839 B CN 111620839B
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吴彦超
陈伟强
李惠静
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Weihai Marine Biological Medicine Industry Technology Research Institute Co ltd
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Abstract

本发明涉及一种金属催化下的串联合成苯基吡咯烷衍生物的制备方法。所制备的苯基吡咯烷衍生物结构式如附图1所示。制备方法：N,N‑二烯丙基苯胺类化合物，Grubbs催化剂、还原铁粉以及反应溶剂，反应温度设定为40 oC、氢气氛围下充分搅拌反应8‑10小时。TLC监测反应结束后进行淬灭，用有机溶剂萃取，干燥，过滤，浓缩，柱层析提纯，得到苯基吡咯烷衍生物，产率在62～81%。本发明使用一锅法串联合成苯基吡咯烷衍生物，原料易得，操作简单，重复性好，而且反应条件温和、适合工业化生产。

Description

一种金属催化下的串联合成苯基吡咯烷衍生物的制备方法
技术领域
本发明涉及一种金属催化下的串联合成苯基吡咯烷衍生物的制备方法。
背景技术
苯基吡咯烷衍生物在自然界中非常丰富，因为它们的结构亚单位存在于天然产品，如维生素、激素、抗生素和生物碱、药物、除草剂、染料等许多化合物，而且它们也是合成杂环化合物的基础组成部分。近年来，对吡咯烷类化合物的合成反应的研究比较热门。Rajender S. Varma研究小组使用苯胺类与二卤代类化合物加入碳酸钾，在微波作用下合成苯基吡咯烷衍生物( Journal of Organic Chemistry, 71(1), 135-141; 2006)。Sukbok Chang研究小组使用四氢吡咯与溴苯类在二(1,5-环辛二烯)四氟硼酸铑催化剂催化下，加入叔丁醇钠，乙二醇二甲醚作溶剂，在80℃反应12小时合成苯基吡咯烷衍生物(Organic Letters, 12(7), 1640-1643; 2010)。Feng Shi研究小组使用苯胺类与二醇类化合物反应，在镍铜铁氧化物催化下，二甲苯作溶剂加热回流24小时合成苯基吡咯烷衍生物 (Chemistry – An European Journal, 19(11), 3665-3675; 2013)。RajendraSrivastava 研究小组使用四氢吡咯苯硼酸类与苯硼酸类化合物反应，在一价铜的金属有机框架化合物催化下，甲醇作溶剂，室温下反应合成苯基吡咯烷衍生物 (TetrahedronLetters, 55(38), 5256-5260; 2014)。Feng Wang研究小组则使用苯胺类与四氢呋喃反应，在氢碘酸催化下，150℃反应16小时合成该类化合物 (Catalysis Communications,94, 56-59; 2017)。而本发明以N,N-二烯丙基苯胺类化合物为原料，在Grubbs催化剂作用下，使用还原铁粉合成苯基吡咯烷衍生物。相比较而言，本发明使用一锅法串联合成苯基吡咯烷衍生物，原料易得，操作简单，重复性好，而且反应条件温和、适合工业化生产。
发明内容
本发明目的在于提供一种金属催化下的串联合成苯基吡咯烷衍生物的制备方法。
为实现上述目的，本发明提供的苯基吡咯烷衍生物结构如图1所示，其中R为氢原子、烷基、烷氧基、卤素、乙酰基、硝基；本发明提供的制备方法，主要步骤是：N,N-二烯丙基苯胺类化合物，Grubbs催化剂、还原铁粉以及反应溶剂，反应温度设定为40 oC、氢气氛围下充分搅拌反应8-10小时。TLC监测反应结束后进行淬灭，用有机溶剂萃取，干燥，过滤，浓缩，柱层析提纯，得到苯基吡咯烷衍生物，产率在62～81%。所得化合物经核磁共振谱图（1H-NMR和13C-NMR）确认，结构无误。
本发明采用N,N-二烯丙基苯胺类化合物可以由苯胺类和烯丙基溴合成。
本发明采用的催化剂为Grubbs一代催化剂和Grubbs二代催化剂。
本发明采用的溶剂为甲醇，乙酸乙酯，二氯甲烷，1,2-二氯乙烷，最佳溶剂为甲醇。
本发明采用的还原剂为还原铁粉，还原锌粉，钯碳，最佳还原剂为还原铁粉。
本发明的柱层析所用的洗脱剂是石油醚和乙酸乙酯等。
附图说明
图1为苯基吡咯烷衍生物的结构图；
图2为反应的具体过程图。
具体实施方式
其反应过程如图2所示，图2反应式中：其中R为氢原子、烷基、烷氧基、卤素、乙酰基、硝基。
具体制备方法举例1：0.1毫摩尔N,N-二烯丙基苯胺，0.005毫摩尔Grubbs一代催化剂， 0.02毫摩尔还原铁粉和1.0毫升甲醇混合在一起，反应温度设定为40 oC、氢气氛围下反应8小时。反应结束后用饱和食盐水溶液淬灭，用有机溶剂萃取，干燥，过滤，浓缩，柱层析提纯，得到1-苯基吡咯烷，收率为80%。核磁共振氢谱1HNMR (400 MHz,CDCl3) δ7.28 (t, J= 7.6 Hz, 2H), 6.71 (t, J = 7.2 Hz, 1H), 6.63 (d, J = 8.0 Hz, 2H), 3.34 (s,4H), 2.05 (s, 4H)；核磁共振碳谱13C NMR (100 MHz, CDCl3) δ147.9, 129.1, 115.3,111.6, 47.5, 25.4。
具体制备方法举例2：0.1毫摩尔N,N-二烯丙基-3-氯苯胺，0.005毫摩尔Grubbs一代催化剂， 0.02毫摩尔还原铁粉和1.0毫升甲醇混合在一起，反应温度设定为40 oC、氢气氛围下反应10小时。反应结束后用饱和食盐水溶液淬灭，用有机溶剂萃取，干燥，过滤，浓缩，柱层析提纯，得到1-（3-氯苯基）吡咯烷，收率为73%。核磁共振氢谱1HNMR (400 MHz,CDCl3) δ7.11 (t, J = 8.0 Hz, 1H), 6.62-6.60 (m, 1H), 6.52 (t, J = 2.2 Hz,1H), 6.43-6.41 (m, 1H), 3.26 (d, J = 6.6 Hz, 4H), 2.02-1.99 (m, 4H)；核磁共振碳谱13C NMR (100 MHz, CDCl3) δ148.8, 134.9, 130.0, 115.1, 111.4, 109.8, 47.6,25.4。
具体制备方法举例3：0.1毫摩尔N,N-二烯丙基-4-溴苯胺，0.005毫摩尔Grubbs一代催化剂， 0.02毫摩尔还原铁粉和1.0毫升甲醇混合在一起，反应温度设定为40 oC、氢气氛围下反应8小时。反应结束后用饱和食盐水溶液淬灭，用有机溶剂萃取，干燥，过滤，浓缩，柱层析提纯，得到1-（4-溴苯基）吡咯烷，收率为75%。核磁共振氢谱1HNMR (400 MHz,CDCl3)δ7.30 (d, J = 9.2 Hz, 2H), 6.45 (d, J = 9.2 Hz, 2H), 3.26 (t, J = 6.6 Hz,4H), 2.04-2.01 (m, 4H)；核磁共振碳谱13C NMR (100 MHz, CDCl3) δ146.8, 131.7,113.2, 107.1, 47.7, 25.5。
具体制备方法举例4：0.1毫摩尔1-（4-（二烯丙基氨基）苯基）乙烷-1-酮，0.005毫摩尔Grubbs一代催化剂， 0.02毫摩尔还原铁粉和1.0毫升甲醇混合在一起，反应温度设定为40 oC、氢气氛围下反应10小时。反应结束后用饱和食盐水溶液淬灭，用有机溶剂萃取，干燥，过滤，浓缩，柱层析提纯，得到1-（4-（吡咯烷-1-基）苯基）乙烷-1-酮，收率为71%。核磁共振氢谱1HNMR (400 MHz,CDCl3) δ7.86 (d, J = 9.2 Hz, 2H), 6.51 (d, J = 8.8 Hz,2H), 3.38-3.35 (m, 4H), 2.50 (s, 3H), 2.05-2.02 (m, 4H)；核磁共振碳谱13C NMR(100 MHz, CDCl3) δ196.3, 151.0, 130.7, 124.9, 110.6, 47.5, 25.9, 25.4。
本发明涉及一种金属催化下的串联合成苯基吡咯烷衍生物的制备方法，以N,N-二烯丙基苯胺类化合物为原料，使用一锅法串联合成苯基吡咯烷衍生物，原料易得，操作简单，重复性好，而且反应条件温和、适合工业化生产。上述具体实施举例仅是本发明的较佳实例而已，并非是对本发明作其它形式的限制。。

Claims (3)

1.一种苯基吡咯烷衍生物的合成方法，主要步骤是：
a) N,N-二烯丙基苯胺类化合物
Figure DEST_PATH_IMAGE001
，Grubbs催化剂、还原铁粉以及反应溶剂，反应温度为40 ºC、氢气氛围下充分搅拌反应8−10小时，所述的Grubbs催化剂为Grubbs一代催化剂
Figure 63885DEST_PATH_IMAGE002
或Grubbs二代催化剂
Figure DEST_PATH_IMAGE003
；
b) TLC监测反应结束后进行淬灭，用有机溶剂萃取，干燥，过滤，浓缩；
c) 柱层析提纯，得到苯基吡咯烷衍生物
Figure 325233DEST_PATH_IMAGE004
，其中R为氢原子、烷基、烷氧基、卤素、乙酰基。
2.根据权利要求1所述的苯基吡咯烷衍生物的合成方法，其特征在于：所述的反应溶剂为甲醇，乙酸乙酯，二氯甲烷，1,2-二氯乙烷。
3.根据权利要求1所述的苯基吡咯烷衍生物的合成方法，其特征在于：所述的N,N-二烯丙基苯胺类与催化剂的摩尔比为1:0.05，N,N-二烯丙基苯胺类与还原剂的摩尔比为1:0.2。
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Citations (1)

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CN109970616A (zh) * 2019-04-19 2019-07-05 哈尔滨工业大学（威海） 一种过渡金属钌催化下的n-酰基吡咯衍生物的制备方法

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CN109970616A (zh) * 2019-04-19 2019-07-05 哈尔滨工业大学（威海） 一种过渡金属钌催化下的n-酰基吡咯衍生物的制备方法

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