Journal of Organic Chemistry Research
Vol.05 No.02(2017), Article ID:20932,7 pages
10.12677/JOCR.2017.52014

Aza-Michael Addition of Chalcone with Benzotriazole Catalyzed by MCM-41 Immobilized H3PW12O40

Jinghui Yang, Liuzhuang Xing, Shaolei Xie, Xuejian Xing, Yadong Hou, Yang Wu, Yonghai Hui*

College of Chemistry and Chemical Engineering, Xinjiang University, Urumqi Xinjiang

*通讯作者。

Received: May 17th, 2017; accepted: Jun. 9th, 2017; published: Jun. 12th, 2017

ABSTRACT

In this paper, mesoporous siliceous material MCM-41 supported H3PW12O40 (PW) could act as an efficient catalyst for the aza-Michael addition reaction of chalcone with benzotriazole. As can be seen from a serial of reaction conditions, the ratio of PW and MCM-41 plays a critical role in the reaction, and the best catalyzed result was achieved when using 50 wt% PW/MCM-41, and the yield was up to 98%. All the products were confirmed by NMR techniques. Moreover, the catalyst was also found to exhibit better recyclability.

Keywords:MCM-41, Phosphoric Acid, Benzotriazole, Chalcone, Michael Addition

介孔分子筛MCM-41固载磷钨酸催化苯并三氮唑与查尔酮的氮杂迈克加成反应研究

杨敬辉,邢刘庄,谢绍雷,邢雪建,侯亚东,吴阳,惠永海*

新疆大学化学化工学院,新疆 乌鲁木齐

收稿日期:2017年5月17日;录用日期:2017年6月9日;发布日期:2017年6月12日

摘 要

以介孔分子筛MCM-41固载磷钨酸为催化剂,对苯并三氮唑与查尔酮进行了氮杂迈克加成的催化研究。经过条件筛选,发现MCM-41中的磷钨酸负载量对该反应体系有很大的影响,其中50 wt%的磷钨酸负载量更有利于反应的进行,产率可达98%。通过NMR对产物结构进行了表征,并且催化剂具有一定的回收再利用效果。

关键词 :MCM-41,磷钨酸,苯并三氮唑,查尔酮,迈克加成

Copyright © 2017 by authors and Hans Publishers Inc.

This work is licensed under the Creative Commons Attribution International License (CC BY).

http://creativecommons.org/licenses/by/4.0/

1. 引言

含氮杂环化合物及其衍生物被广泛应用于有机合成、医药和生物等领域。缺电子的唑类化合物是药物中常见的结构片段,如,意大利A. Carta研究组合成的3-芳基-2-(1H-苯并三氮唑-1-基)丙烯腈类化合物具有抗类风湿、抗增生、抗肿瘤和抗结核等作用 [1] [2] ;台湾中央研究院的翁启惠课题组发现苯并三氮唑芳香酯类化合物对SARS病毒有很强的抑制效果 [3] 。氮杂迈克加成是形成C-N键的重要方法之一,其中,查尔酮与唑类化合物的共轭加成是生成C- N键的很好的反应。据文献报道,有N-O-Sc [4] 、Salen-Al [5] 、咪唑啉酮 [6] 、双氨基硫脲 [7] 、手性磷酸 [8] 和纳米金属 [9] 等类催化剂能够很好地催化氮杂迈克加成,但是寻找简单易得,原子经济型的催化剂依然是人们追求的目标。

随着社会环保意识和能源节约意识的增强,传统催化剂已不符合绿色化学的发展要求,因此,固载型催化剂已成为有机化学的一个研究热点。本课题组前期报道过一系列介孔分子筛MCM-41固载型催化剂催化有机反应,取得了较好的结果 [10] [11] [12] [13] 。在这里,我们研究了MCM-41固载磷钨酸为催化剂,催化查尔酮与苯并三氮唑的氮杂麦克加成反应,并得到很高的产率,最高可达98% (图1)。

2. 实验部分

2.1. 试剂与仪器

Varian inova-400型核磁共振仪(TMS为内标,CDCl3为溶剂,单位为ppm);RV10型旋转蒸发仪;X-4数字显示显微熔点测定仪;BRUKER EQUINX55型红外光谱仪(KBr压片)测定;ZF-2型三用紫外仪;柱层析用硅胶(200-300目,青岛海洋化工厂);所用试剂及溶剂均为市售分析纯,用前未经处理。

Scheme 1. The aza-Michael addition reaction

图1. 氮杂迈克加成反应

2.2. 目标化合物3a-3m的合成结构分析

目标化合物的合成(以1a的合成为例):将查尔酮(0.1 mmol,0.0208 g)、苯并三氮唑(0.11 mmol,0.0131 g)和MCM-41固载磷钨酸(0.005 g)溶于THF (1.0 mL)中,室温搅拌12 h,TLC检测反应。反应完毕后,柱层析(乙酸乙酯:石油醚 = 1:5洗涤)分离纯化得目标产物。目标化合物的表征如下:

3a [4] : 3-苯基-3-(1H-苯并[1,2,3]三氮唑-1-基)-2-苯丙酮,无色油状物,产率85%,1H NMR (400 MHz, CDCl3): δ 3.88 (dd, J = 12.8, 5.2 Hz, 1H), 4.90 (dd, J = 18.4, 5.2 Hz, 1H), 6.57 (dd, J = 8.8, 4.8 Hz, 1H), 7.32-7.60 (m, 11H), 7.98-8.04 (m, 3H).

3b [4] : 3-(1H-苯并[1,2,3]三氮唑-1-基)-3-苯基-1-(4-氯苯基)丙烷-1-酮,黄色油状物,92%,1H NMR (400 MHz, CDCl3): δ 3.79 (dd, J = 5.2, 4.8 Hz, 1H), 4.81 (dd, J = 9.2, 8.8 Hz, 1H), 6.55 (d, J = 4.8 Hz, 1H), 7.30-7.51 (m, 10H), 7.93-8.04 (m, 3H).

3c: 3-(1H-苯并[1,2,3]三氮唑-1-基)-3-苯基-1-(4-溴苯基)丙烷-1-酮, 黄色油状物,85%,1H NMR (400 MHz, CDCl3): δ 3.78 (dd, J = 8.0, 4.0 Hz, 1H), 4.08 (dd, J = 8.0, 8.0 Hz, 1H), 4.80 (dd, J = 8.0, 12.0 Hz, 1H), 6.52 (dd, J = 4.0, 8.0 Hz, 1H), 7.26-7.61 (m, 9H), 7.84-8.03 (m, 3H); 13C NMR (400 MHz, CDCl3) δ: 44.34, 58.32, 109.85, 119.83, 124.09, 126.64, 127.39, 128.55, 128.87, 129.09, 129.70, 131.99, 134.88, 138.81, 144.57, 146.11, 157.84, 194.95.

3d: 3-(1H-苯并[1,2,3]三氮唑-1-基)-3-苯基-1-(4-甲基苯基)丙烷-1-酮, 黄色油状物,92%,1H NMR (400 MHz, CDCl3): δ 2.38 (s, 3H), 3.85 (dd, J = 4.0, 4.0 Hz, 1H), 4.79 (dd, J = 8.0, 8.0 Hz, 1H), 6.57 (dd, J = 4.0, 4.0 Hz, 1H), 7.22-7.54 (m, 10H), 7.88-8.03 (m, 3H) ; 13C NMR (400 MHz, CDCl3) δ: 21.54, 44.15, 58.25, 109.83, 119.67, 123.90, 126.64, 127.19, 128.21, 128.31, 128.90, 129.23, 133.61, 139.02, 144.38, 145.99, 195.32.

3e [4] : 3-(1H-苯并[1,2,3]三氮唑-1-基)-3-苯基-1-(4-甲氧基苯基)丙烷-1-酮, 黄色油状物,84%,1H NMR (400 MHz, CDCl3): δ 3.81 (dd, 5.2, 2.4 Hz, 1H), 3.87 (s, 3H), 4.76 (dd, J = 8.8, 8.8 Hz, 1H), 6.56 (dd, J = 4.8, 4.8 Hz, 1H), 6.91-6.93 (m, 2H), 7.26-7.54 (m, 8H), 7.96-8.03 (m, 3H).

3f [4] : 3-(1H-苯并[1,2,3]三氮唑-1-基)-3-苯基-1-(呋喃-2-基)丙烷-1-酮, 黄色油状物,73%,1H NMR (400 MHz, CDCl3): δ 3.76 (dd, J = 5.2, 5.2 Hz, 1H), 4.66 (dd, J = 9.2, 9.2 Hz, 1H), 6.53-6.55 (m. 2H), 7.27-7.40 (m, 5H), 7.41-7.42 (m, 3H), 7.49-7.52 (m, 1H), 7.59-7.60 (m, 1H), 8.02-8.04 (m, 1H).

3g [4] : 3-(1H-苯并[1,2,3]三氮唑-1-基)-3-(4-氟苯基)-1-苯基丙烷-1-酮黄色油状物,96%,1H NMR (400 MHz, CDCl3): δ 3.90 (dd, J = 4.0, 4.0 Hz, 1H), 4.76 (dd, J = 8.0, 8.0 Hz, 1H), 6.54 (dd, J = 8.0, 8.0 Hz, 1H), 7.01 (m, 1H), 7.43-7.57 (m, 8H), 7.98-8.04 (m, 3H).

3h [4] : 3-(1H-苯并[1,2,3]三氮唑-1-基)-3-(4-氯苯基)-1-苯基丙烷-1-酮, 黄色油状物,77%,1H NMR (400 MHz, CDCl3): δ 3.86 (dd, J = 4.0, 4.0 Hz, 1H), 4.83 (dd, J = 8.0, 8.0 Hz, 1H), 6.56 (dd, J = 4.0, 4.0 Hz, 1H), 7.26-7.58 (m, 10H), 7.98-8.04 (m, 3H).

3i [4] : 3-(1H-苯并[1,2,3]三氮唑-1-基)-3-(4-溴苯基)-1-苯基丙烷-1-酮, 黄色油状物,80%,1H NMR (400 MHz, CDCl3): δ 3.85 (dd, J = 4.0, 4.0 Hz, 1H), 4.79 (dd, J = 8.0, 5.2 Hz, 1H), 6.55 (dd, J = 8.0, 8.0 Hz, 1H), 7.26-7.54 (m, 10H), 7.88-7.95 (m, 2H), 8.00-8.03 (m, 1H).

3j [4] : 3-(1H-苯并[1,2,3]三氮唑-1-基)-3-(4-甲氧基苯基)-1-苯基丙烷-1-酮, 黄色油状物,90%,1H NMR (400 MHz, CDCl3): δ 3.75 (s, 3H), 3.79 (dd, J = 4.0, 4.0 Hz, 1H), 4.75 (dd, J = 8.0, 8.0 Hz, 1H), 6.47 (dd, J = 4.0, 4.0 Hz, 1H), 6.83 (d, J = 8.0 Hz, 2H), 7.31-7.51 (m, 8H), 7.92-8.03 (m, 3H).

3k [4] : 3-(1H-苯并[1,2,3]三氮唑-1-基)-3-(4-氟苯基)-1-(2-萘基)丙烷-1-酮, 黄色油状物,87%,1H NMR (400 MHz, CDCl3): δ 3.98 (dd, J = 5.2, 5.2 Hz, 1H), 4.94 (dd, J = 8.8, 8.8 Hz, 1H), 6.73-6.79 (m, 1H), 7.28-7.36 (m, 1H), 7.37-7.57 (m, 8H), 7.77-7.81 (m, 3H), 7.86-7.87 (d, J = 1.2 Hz, 1H), 8.00-8.05 (m, 3H).

3l: 3-(1H-苯并[1,2,3]三氮唑-1-基)-3-(4-氯苯基)-1-(4-甲氧基苯基)丙烷-1-酮, 黄色油状物,87%,1H NMR(400 MHz, CDCl3): δ 3.85 (s, 3H), 3.85 (dd, J = 4.0, 4.0 Hz, 1H), 4.88 (dd, J = 8.0, 8.0 Hz, 1H), 6.53 (dd, J = 4.0, 4.0 Hz, 1H), 6.90-6.93 (m, 2H), 7.26-7.53 (m, 7H), 7.94-8.04 (m, 3H); 13C NMR (400 MHz, CDCl3) δ: 43.95, 55.50, 57.76, 109.70, 113.87, 119.91, 124.17, 127.51, 128.22, 129.13, 129.19, 130.55, 132.91, 134.34, 137.66, 163.97, 194.02.

3m: 3-(1H-苯并[1,2,3]三氮唑-1-基)-3-(4-甲氧基苯基)-1-(4-氯苯基)丙烷-1-酮, 黄色油状物,83%,1H NMR (400 MHz, CDCl3): δ 3.85 (s, 3H), 3.86 (dd, J = 8.0, 4.0 Hz, 1H), 4.68 (dd, J = 8.0, 8.0 Hz, 1H), 6.53 (dd, J = 4.0, 4.0 Hz, 1H), 6.90-6.93 (m, 2H), 7.26-7.52 (m, 7H), 7.94-8.03 (m, 3H); 13C NMR (400 MHz, CDCl3) δ: 43.90, 55.46, 57.72, 109.68, 113.83, 119.86, 124.13, 127.47, 128.19, 129.08, 129.15, 130.51, 132.87, 134.29, 137.64, 146.05, 163.92, 193.98.

3. 结果与讨论

3.1. 反应条件的优化

以苯亚甲基苯乙酮和苯并三氮唑的反应来优化反应条件,选择水作为溶剂,考察不同催化剂对反应的影响(表1)。我们发现无催化剂和介孔分子筛MCM-41催化反应都得不到目标产物;当以磷钨酸(PW)和磷钼酸(PM)为催化剂时,反应能顺利进行,但是反应产率不高。将MCM-41固载不同量的杂多酸时,其催化效果有很大差别。当磷钨酸在MCM-41(PW/MCM-41)中的负载量为50 wt%时,反应产率提高到36%,而继续提高磷钨酸的负载量,分子筛的孔道空间缩小,不利反应的进行,从而使产率有所下降;同样的50 wt%的PMA/MCM-41催化反应时,只能得到25%的产率。然后,考察了不同溶剂对反应的影响(表1,Entries 11-16)。甲醇、甲苯和乙酸乙酯为溶剂时,均得不到反应产物.醚类溶剂有利于反应的进行,其中在THF中,反应产率最高,79%。在调节反应底物配比中,当n(查尔酮):n(苯并三氮唑) = 1:1.1时,产率可以达到82%,增加和降低查尔酮的量都不能提高反应产率。而改变反应体系浓度(THF量为1 mL)时,反应产率最高。最后考察了反应时间对反应的影响,缩短反应时间会使产率降低,而延长反应时间并没有提高产物的产率。最终确定的最佳反应条件为:查尔酮(0.1 mmol)、苯并三氮唑(0.11 mmol)及50 wt% PW/MCM-41 (0.005 g)在THF (1.0 mL)中室温反应12 h。

3.2. 反应底物的扩展

在最优条件下研究了50 wt% PW/MCM-41催化不同查尔酮与苯并三氮唑的迈克加成反应(表2)。对于查尔酮,苯环上R1和R2不论是供电子还是吸电子取代基,反应都能得到很高的产率(Entries 1-13)。当R1或R2上的取代基为同一主族元素时,如F、Cl和Br,随着原子电负性的降低,原子半径的增大,反应活性逐渐降低(Entries 2-3,7-9);当R1是杂环取代基时,反应可以得到73%的产率(Entry 6);当2-萘醛制备的查尔酮参与此反应时,反应也可以得到很好的产率,87% (Entry 11)。最后,我们进行了反应放大量实验研究,所有反应物均放大到克级,反应产率没有明显变化(entry14)。

3.3. 催化剂的重复使用

介孔分子筛属于非均相催化剂,其最大特点就是能够重复再利用。在对PM/MCM-41催化剂进行催化循环实验考察中,从表3结果所示,催化剂在前三次的循环实验中催化活性保持很好,但从循环第四次实验就有明显的失活,循环到六次时,反应只能得到34%的产率。导致产率急剧下降的原因可能是由于有机溶剂THF能够溶解一部分磷钨酸,使介孔分子筛的孔道空间变大,催化剂的活性位点减少造成的。

Table 1. Different condition effect on the reaction

表1. 不同反应条件的优化a

a反应条件:查尔酮1 (0.10 mmol),苯并三氮唑2a (0.10 mmol),0.005 g催化剂在0.5 mL溶剂中室温反应。b柱层析产率。cn(查尔酮):n(苯并三氮唑) = 1:1.1。dTHF (1 mL)。

Table 2. Aza-Michael addition reaction by PWA/MCM-41

表2. PWA/MCM-41催化氮杂迈克加成反应a

a反应条件:查尔酮1 (0.10 mmol),苯并三氮唑2a (0.11 mmol),0.005 g催化剂在溶剂THF中室温反应。b柱层析产率。c反应规模扩大100倍。

Table 3. The reusability of PW/MCM-41

表3. PMA/MCM-41的重复使用性a

a反应条件:查尔酮1 (0.10 mmol),苯并三氮唑2a (0.11 mmol),0.005 g催化剂在溶剂THF中室温反应。b柱层析产率。

Scheme 2. Proposed reaction mechanism for the reaction

图2. 反应可能机理

3.3. 反应机理

我们对MCM-41固载杂多酸催化有机反应的研究中发现 [12] ,我们提出了可能反应机理,见图2。介孔分子筛吸附杂多酸后,形成了一个微反应器,当查尔酮进入微反应器后,形成包结络合物 [14] ,苯并三氮唑的NH对查尔酮乙烯基表现出较强的亲核进攻性,形成了氮杂迈克加成产物。该反应机理中,MCM-41中固载的杂多酸产生催化诱导作用有待于进一步研究,目前课题组还无法对在微反应器中以自包结状态进行优化计算,以后会开展此项工作。

4. 结论

本文利用介孔分子筛MCM-41固载杂多酸作为催化剂,有效催化了苯并三氮唑和查尔酮的氮杂迈克加成反应。通过反应条件优化,发现MCM-41固载50 wt%负载量的磷钨酸时,能够得到良好的收率,最高可达98%。最后,我们考察了催化剂的回收再利用,发现催化剂具有一定的循环再催化效果。

致谢

国家自然科学基金(Nos. 21362036, 21161026)。

文章引用

杨敬辉,邢刘庄,谢绍雷,邢雪建,侯亚东,吴 阳,惠永海. 介孔分子筛MCM-41固载磷钨酸催化苯并三氮唑与查尔酮的氮杂迈克加成反应研究
Aza-Michael Addition of Chalcone with Benzotriazole Catalyzed by MCM-41 Immobilized H3PW12O40[J]. 有机化学研究, 2017, 05(02): 107-113. http://dx.doi.org/10.12677/JOCR.2017.52014

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  11. 11. 惠永海, 石伟, 谢绍雷, 王长春, 解正峰.水溶液中介孔分子筛MCM-41负载磷钨酸(PW)催化三组分Mannich反应研究[J]. 有机化学, 2014, 34(6): 1212.

  12. 12. Kui, F., Hui,Y.H., Hu, X.M., Shi, W., Pang, H.X. and Xie, Z.F. (2015) PMoA/MCM-41 Catalyzed Aza-Michael Reaction: Special Effects of Mesoporous Nanoreactor on Chemical Equilibrium and Reaction Rate through Surface Energy Transformation. New Journal of Chemistry, 39, 5916. https://doi.org/10.1039/C5NJ01507C

  13. 13. 邢雪建, 樊馗, 庞海霞, 吴阳, 杨敬辉, 石伟, 解正峰, 惠永海. 介孔分子筛MCM-41 固载席夫碱与醋酸锌共催化“一锅法”合成噻唑啉酮衍生物[J]. 有机化学, 2016, 36(8): 1942.

  14. 14. 朱庆英, 沈海民, 纪红兵. β-环糊精衍生物诱导H2O2水相不对称环氧化trans-查尔酮[J]. 有机化学, 2016, 36(8): 1907.

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