Moradi Farzaneh, Abdoli-Senejani Masumeh, Ramezani Majid
Department of Chemistry, Faculty of Science, Islamic Azad University, Arak Branch, Arak, Iran.
Curr Org Synth. 2020;17(1):46-54. doi: 10.2174/1570179416666191118110316.
A wide variety of dihydropyrimidins (DHPMs) exhibit pharmacological and biological activities. Herein, an efficient one-pot synthesis of some 3, 4-dihydropyrimidin-2(1H)-one derivatives is reported using Fe3O4 @SiO2-Pr-INH.
Recently, several catalysts have been used to improve the Biginellis-reaction. However, some of these catalysts have imperfections. Herein, a convenient method for the synthesis of 3, 4-dihydropyrimidin- 2(1H)-ones and their sulfur derivatives using Fe3O4 @SiO2-Pr-INH is reported.
Firstly, the catalyst was synthesized through a simple four-step method. The Fe3O4 MNPs were synthesized using the chemical co-precipitation method, coated with a layer of silica using TEOS, and then functionalized with CPTMS. Subsequently, a nucleophilic substitution of Cl by isoniazid resulted in the formation of the magnetic Fe3O4@SiO2-Pr-INH. After the preparation and characterization of Fe3O4@SiO2-Pr-INH, its catalytic activity was studied in the synthesis of 3, 4-dihydropyrimidin-2(1H)-one derivatives. Following the optimization of the reaction conditions, several 3, 4-dihydropyrimidin-2(1H)-one derivatives were synthesized by the reaction of ethyl acetoacetate or acetylacetone, thiourea or urea and aromatic aldehydes at 80 °C under solvent-free conditions.
Isoniazid-functionalized Fe3O4 magnetic nanoparticles (Fe3O4@SiO2-Pr-INH) were prepared using Fe3O4 with silica layer and their surface was modified with isoniazid. They were characterized successfully by infrared spectroscopy, powder X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray spectroscopy and were used for the synthesis of some 3, 4-dihydropyrimidin-2(1H)-one derivatives as catalysts. Aromatic aldehydes with electron-donating or electron-withdrawing groups afforded 3, 4- dihydropyrimidin-2(1H)-ones and their sulfur derivatives in good to excellent yields in short reaction times.
Isoniazid-functionalized Fe3O4 magnetic nanoparticles (Fe3O4@SiO2-Pr-INH) were used as an efficient catalyst for Biginelli-type synthesis of 3, 4-dihydropyrimidin-2(1H)-ones and 3, 4-dihydropyrimidin- 2(1H)-thiones in good to excellent yields and short reaction times. It is noteworthy that this method has several advantages such as simple experimental procedures, the absence of solvent, environmentally benign process, stability and reusability of the catalyst.
多种二氢嘧啶（DHPMs）具有药理和生物活性。本文报道了使用Fe3O4@SiO2-Pr-INH高效一锅法合成一些3,4-二氢嘧啶-2(1H)-酮衍生物。
近年来，几种催化剂已被用于改进Biginelli反应。然而，其中一些催化剂存在缺陷。本文报道了一种使用Fe3O4@SiO2-Pr-INH合成3,4-二氢嘧啶-2(1H)-酮及其硫衍生物的简便方法。
首先，通过简单的四步法合成催化剂。采用化学共沉淀法合成Fe3O4磁性纳米粒子（MNPs），用正硅酸乙酯（TEOS）包覆一层二氧化硅，然后用3-氯丙基三甲氧基硅烷（CPTMS）进行功能化。随后，异烟肼对氯进行亲核取代，形成磁性Fe3O4@SiO2-Pr-INH。在制备和表征Fe3O4@SiO2-Pr-INH后，研究了其在合成3,4-二氢嘧啶-2(1H)-酮衍生物中的催化活性。在优化反应条件后，在无溶剂条件下，于80℃通过乙酰乙酸乙酯或乙酰丙酮、硫脲或尿素与芳香醛的反应合成了几种3,4-二氢嘧啶-2(1H)-酮衍生物。
使用带有二氧化硅层的Fe3O4制备了异烟肼功能化的磁性纳米粒子（Fe3O4@SiO2-Pr-INH），并用异烟肼对其表面进行了修饰。通过红外光谱、粉末X射线衍射、扫描电子显微镜、能量色散X射线光谱对其进行了成功表征，并将其用作催化剂合成了一些3,4-二氢嘧啶-2(1H)-酮衍生物。带有供电子或吸电子基团的芳香醛在短反应时间内以良好至优异的产率得到3,4-二氢嘧啶-2(1H)-酮及其硫衍生物。
异烟肼功能化的磁性纳米粒子（Fe3O4@SiO2-Pr-INH）被用作高效催化剂，用于Biginelli型合成3,4-二氢嘧啶-2(1H)-酮和3,4-二氢嘧啶-2(1H)-硫酮，产率良好至优异，反应时间短。值得注意的是，该方法具有几个优点，如实验步骤简单、无溶剂、环境友好、催化剂稳定性好且可重复使用。
