LED光诱导下咪唑并吡啶氰甲基化反应用于本科实验教学的探索

可见光催化的有机反应具有高效、条件温和、操作简单、催化剂用量少等优点,近年来受到广泛关注。以咪唑[1,2-a]吡啶杂环为骨架的化合物表现出丰富多样的生物活性,如抗炎、抗病毒活性、抗原生虫药、细胞周期蛋白依赖性激酶抑制剂等。3-氰甲基-2-苯基咪唑并[1,2-a]吡啶是合成具有抗抑郁作用的药物唑吡坦的关键中间体。我们在前期的研究工作中,以2-苯基咪唑并[1,2-a]吡啶和溴乙腈为原料,通过可见光诱导,在光催化剂fac-Ir(ppy)3的作用下,合成了3-氰甲基-2-苯基咪唑并[1,2-a]吡啶。本文以此反应为基础,通过将可见光催化这一新型的方法运用于本科实验教学,拓宽本科生的视野,增加其对有机化学实验的兴趣,并掌握微量化学实验的基本操作和相关仪器的使用方法。本设计实验使用LED灯作为光源,避免了剧毒试剂的使用,符合绿色化学理念,具备制备方法简单、生产成本低、产物收率高、重复性良好等优点。

Study on the LED Light Induced Cyanomethylation of Imidazopyridine Used in the Teaching of Undergraduate Laboratory Course

Visible light-catalyzed organic reactions have the advantages of high efficiency, operational simplicity, low loading of catalysts under mild conditions, and have received much attention in recent years. The compounds based on the skeleton of imidazo[1, 2-a]pyridine show an impressively wide range of biological activities, such as anti-inflammatory, antiviral activity, antiprotozoal agents, inhibitors of cyclin-dependent kinases, etc. 3-Cyanomethyl-2-phenylimidazo[1, 2-a]pyridine is a key intermediates for the synthesis of the antidepressant drug zolpidem. In our previous work, 3-cyanomethyl-2-phenylimidazo[1, 2-a]pyridine was synthesized via a visible light-promoted reaction of 2-phenyl-imidazo[1, 2-a]pyridine with bromoacetonitrile using fac-Ir(ppy)₃ as the photocatalyst. Based on the reaction, herein, the new method about visible light-catalysis was applied to laboratory teaching for broadening the horizons of undergraduates and improving their interests on organic chemistry experiments. Meanwhile, it will help the undergraduates master the basic operations of microchemistry experiments and the use of related instruments. Moreover, this experiment meets the requirements of green chemistry, since it is performed under LED lamp radiation in the absence of toxic reagents. This method also features operational simplicity, low cost, high yield, and good repeatability, etc.