Department of Chemistry, Islamic Azad University, Rasht Branch, Rasht,Iran.
Department of Chemistry, Payame Noor University, PO Box 19395-3697 Tehran,Iran.
Comb Chem High Throughput Screen. 2022;25(2):267-273. doi: 10.2174/1386207324999210120194730.
Dihydroquinazolinone derivatives are an important family of fused heterocyclic compounds which possess a wide range of biological, medicinal and pharmacological properties such as anti-tumor, anti-biotic, diuretic, analgesic, anti-hypertonic, anti-pyretic, antidepressant, anti-histamine and vasodilation activities.
So far, some acid catalysts, e.g. p-toluenesulfonic acid, silica sulfuric acid, zinc(II) perfluorooctanoate, gallium(III) triflate, ionic liquid, Al(H2PO4)3, I2, montmorillonite K-10, Amberlyst-15, Al/Al2O3 and Fe3O4 nanoparticles, have been reported to accomplish this threecomponent reaction. Some of these methods have drawbacks such as toxic solvents and catalysts, long reaction time, the use of expensive catalysts and adverse yields.
A mixture of benzaldehydes (1mmol), isatoic anhydride (1 mmol), Glycine (1 mmol) and OImDSA (2 mL) were stirred at room temperature for the required reaction times (1-2 h). The progress of the reaction was monitored by TLC (EtOAc: petroleum ether 1:2). After completion of the reaction, as indicated by TLC, the ionic liquid was separated by extraction with 2×15 mL of water. The solid residue was separated by recrystallization from EtOH. The pure products were collected in 86-97% yields.
Herein, we report the mild synthesis of some derivatives of 2-aryl-quinazolin-4(1H)-ones from isatoic anhydride and Glycine using OImDSA, which has been found to be an efficient synthesis method, with depleted side effects, reduced reaction steps, increased efficiency and curtailed reaction time, in continuation of our research on the synthesis of heterocyclic and pharmaceutical compounds.
In conclusion, we have developed a simple, green and efficient protocol for the synthesis of 2-aryl-quinazolin-4(1H)-ones using OImDSA. Simplicity, easy practice, inexpensive, environmentally friendly and reusable ionic liquid are notable attributes of this new method. To the best of our knowledge, this is the first report on the synthesis of a new library of quinazolin-4(1H)- ones derived from Glycine as a natural substrate based on green chemistry conditions.
二氢喹唑啉酮衍生物是一类重要的稠合杂环化合物，具有广泛的生物、医学和药理学特性，如抗肿瘤、抗生素、利尿、镇痛、抗高渗、解热、抗抑郁、抗组胺和血管扩张活性。
到目前为止，已经报道了一些酸催化剂，例如对甲苯磺酸、硅硫酸、锌(II)全氟辛酸盐、三氟甲磺酸镓、离子液体、Al(H2PO4)3、I2、蒙脱土 K-10、Amberlyst-15、Al/Al2O3 和 Fe3O4 纳米粒子，可用于完成这一三元反应。这些方法中的一些存在缺点，例如使用有毒溶剂和催化剂、反应时间长、使用昂贵的催化剂和不良收率。
将苯甲醛（1mmol）、异邻苯二甲酰亚胺（1mmol）、甘氨酸（1mmol）和 OImDSA（2mL）混合，在室温下搅拌所需的反应时间（1-2h）。通过 TLC（EtOAc：石油醚 1:2）监测反应的进展。反应完成后，根据 TLC 指示，用 2×15mL 水萃取分离离子液体。通过从 EtOH 重结晶分离出固体残留物。以 86-97%的产率收集纯产物。
在此，我们报告了使用 OImDSA 从异邻苯二甲酰亚胺和甘氨酸温和合成一些 2-芳基-喹唑啉-4(1H)-酮衍生物，这是一种高效的合成方法，副作用小，反应步骤减少，效率提高，反应时间缩短，这是我们对杂环和药物化合物合成研究的延续。
总之，我们开发了一种使用 OImDSA 合成 2-芳基-喹唑啉-4(1H)-酮的简单、绿色、高效的新方法。简单、易于实践、成本低、环保且可重复使用的离子液体是这种新方法的显著特点。据我们所知，这是首次报道在绿色化学条件下基于甘氨酸作为天然底物合成新的喹唑啉-4(1H)-酮文库。
