Tazari Mohsen, Kiyani Hamzeh
School of Chemistry, Damghan University, Damghan, Iran.
Curr Org Synth. 2019;16(5):793-800. doi: 10.2174/1570179416666190415105818.
Chromenes and pyran annulated heterocycles are the most common frameworks existing in various biologically active molecules. Due to their beneficial and biological properties, they are eyecatching synthetic targets in the arsenal of organic chemistry. Thus, finding green and efficient methods, as well as searching for a new catalyst for the synthesis of these heterocycles is of interest to organic chemistry researchers.
Sodium malonate as a readily available catalyst was employed aimed at the multicomponent synthesis of numerous 2-amino-4H-chromenes and 2-amino-4H-pyrans in water as a green medium reaction.
The reaction was performed via treatment of aldehydes (1 mmol) with malononitrile/ethyl cyanoacetate (1 mmol) and β-dicarbonyl compounds (1 mmol)/or resorcinol (1 mmol) in water (4 mL) in the presence of sodium malonate (10 mol %) at 70°C. On completion of the reaction (monitored by TLC analysis), the reaction mixture was gradually cooled at room temperature, and the resulting precipitates were collected by filtration, washed with cold ethanol and air-dried to give the corresponding pure products. The solvent was evaporated from the filtrate to recover the catalyst, and the catalyst was reused for subsequent reactions.
In the initial stages, we explored the best reaction conditions using three-component reaction of benzaldehyde, malononitrile, and dimedone as the model reaction. The effects of catalyst loading, temperature, and solvents were explored for this reaction. It was found that the best results were obtained for the synthesis of 2-amino-4H-chromenes and 2-amino-4H-pyran when the three-component reaction was carried out with equivalent molar quantities of each of the reactants in water containing 10 mol% sodium malonate at 70°C for 15 min in 96% yield. After finding optimal conditions, these conditions apply to other reactants and the target heterocyclic products were obtained with excellent yields.
This study describes an efficient, environmentally benign, and clean one-pot, three-component synthesis of 2-amino-4H-chromenes and 2-amino-4H-pyran-3-carboxylates in the presence of sodium malonate as the commercially available catalyst in an aqueous medium at 70°C. High yields, mild reaction conditions, relatively shorter reaction times, use of simple reagents, and no requirement of the ultrasound, microwave, and ball milling techniques are the salient features and benefits of the present method. In addition, the present process is smooth and green.
色烯和吡喃稠合杂环是各种生物活性分子中最常见的骨架。由于它们具有有益的生物特性，因此在有机化学领域中是引人注目的合成目标。因此，寻找绿色高效的方法以及寻找合成这些杂环的新催化剂是有机化学研究人员感兴趣的课题。
使用丙二酸钠作为一种容易获得的催化剂，旨在在水作为绿色介质的反应中多组分合成多种2-氨基-4H-色烯和2-氨基-4H-吡喃。
在70℃下，在丙二酸钠（10mol%）存在下，将醛（1mmol）与丙二腈/氰基乙酸乙酯（1mmol）和β-二羰基化合物（1mmol）/或间苯二酚（1mmol）在水（4mL）中进行反应。反应完成后（通过薄层色谱分析监测），将反应混合物在室温下逐渐冷却，通过过滤收集所得沉淀，用冷乙醇洗涤并空气干燥以得到相应的纯产物。从滤液中蒸发溶剂以回收催化剂，并且该催化剂可重复用于后续反应。
在初始阶段，我们以苯甲醛、丙二腈和达米酮的三组分反应作为模型反应探索了最佳反应条件。研究了该反应中催化剂负载量、温度和溶剂的影响。发现当三组分反应在含有10mol%丙二酸钠的水中，以等摩尔量的每种反应物在70℃下进行15分钟时，合成2-氨基-4H-色烯和2-氨基-4H-吡喃可获得最佳结果，产率为96%。找到最佳条件后，这些条件适用于其他反应物，并以优异的产率获得目标杂环产物。
本研究描述了在70℃的水介质中，以丙二酸钠作为市售催化剂，高效、环境友好且清洁的一锅三组分合成2-氨基-4H-色烯和2-氨基-4H-吡喃-3-羧酸酯的方法。高产率、温和的反应条件、相对较短的反应时间、使用简单的试剂以及不需要超声、微波和球磨技术是本方法的显著特点和优点。此外，本工艺顺畅且绿色。
