Sustainable parts‐per‐million level catalysis with Fe^III: One‐pot cascade synthesis of 2,3‐dihydroquinazolin‐4(1H)‐ones in water

Abstract

A silica-supported iron complex has been identified as a highly active and reusable catalyst for the synthesis of medicinally important 2,3-dihydroquinazolin-4(1H)-ones. The catalyst was fully characterized by various spectroscopic analyses such as Fourier-transform infrared spectroscopy (FT-IR), ultraviolet-visible (UV-VIS), scanning electron microscopy (SEM), scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDX), energy-dispersive spectroscopy (EDS) mapping, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), electron paramagnetic resonance (EPR), inductively coupled plasma atomic emission spectroscopy (ICP-AES), elemental analysis, Brunauer-Emmett-Teller (BET) isotherm and thermogravimetric analysis (TGA) analysis. A diverse library of 2,3-dihydroquinazolin-4(1H)-ones including some new analogues were successfully synthesized in good to excellent yields with parts-per-million (ppm) levels of Fe using water as a solvent. The active catalyst has high turnover number (TON) and turnover frequency (TOF) at the optimized condition, which were 30,087 and 30,087 h −1 , respectively. Ppm level catalysis, wide substrate scope, shorter reaction time, reusability of the catalyst, green solvent media and gram-scale synthesis make this protocol eco-friendly and sustainable.

Anti-TB Evaluation of Novel 2,3-Dihydroquinazolin-4(1H)-Ones and in Silico Studies of The Active Compounds

“…Afterwards, the work was extended for the construction of some novel bis-2,3-dihydroquinazolin-4(1H)-one analogues via Glaser coupling reaction using copper acetate in which 2a-2e were used as starting precursors [24]. All the five reactions gave the desired novel bis-2,3-dihydroquinazolin-4(1H)-ones in good to excellent yields which was reported in our recent work [23]. From 1 H and 13 C NMR spectroscopic analysis, it was confirmed that all these novel bis-2,3-dihydroquinazolin-4(1H)-one analogues were C2-symmetric.…”

“…General method for synthesis of 2,3-dihydroquinazolin-4(1H)-ones (2a-2j) [23] Isatoic anhydride (1 mmol), amines (1.2 mmol), carbonyls (1.2 mmol) and [{SiO2-(acac)}3Fe III ]Cl3 (20 mg, 32.24 ppm Fe) in water (2 mL) were stirred in a flask equipped with a condenser at 80 o C. On completion (monitored by TLC under UV light), the resulting mixture was cooled to room temperature and then the mixture was extracted with ethyl acetate (3 x 10 mL) and washed with H2O (3 x 10 mL). The combined extract was dried over anhydrous Na2SO4.…”

“…The product was purified by column chromatography on silica gel using petroleum General procedure for the synthesis of compounds (3a-3e) [23] A mixture of 2a-2e (1 mmol), piperidine (1 mmol) and Cu(OAc)2•H2O (10 mol%) in CH2Cl2 (2 mL) was stirred in an open air at room temperature for 10 hours. On completion (monitored by TLC under UV light), the resulting mixture was extracted with ethyl acetate (3 x 10 mL) and washed with water (3 x 10 mL).…”

“…Our aim was to synthesize a series of novel derivatives of 2,3-dihydroquinazolin-4(1H)-ones and evaluation of their anti-TB potency. Using our method developed recently [23], we have synthesized ten derivatives of novel 2,3-dihydroquinazolin-4(1H)-ones. Afterwards, the work was extended for the construction of some novel bis-2,3-dihydroquinazolin-4(1H)-one analogues via Glaser coupling reaction using copper acetate in which 2a-2e were used as starting precursors [24].…”

In situfabrication of HDA-mediated NiFe–Fe2O3nanorods: an efficient and recyclable heterogeneous catalyst for the synthesis of 2,3-dihydroquinazolin-4(1H)-ones in water

“…As a part of our continued efforts regarding the development of new synthetic strategies for the construction of 2,3-dihydroquinazolin-4(1H)-ones, [49][50][51][52] herein, we report a novel and efficient protocol for the synthesis of 2,3-dihydroquinazolin-4(1H)ones via the one-pot three-component condensation of isatoic anhydride, amines/ammonium acetate, and carbonyls in the presence of NiFe-Fe 2 O 3 NPs in water. These inexpensive NPs are synthesized for the first time in nanorod morphology assisted by HDA, and its formation mechanism with solid evidences in its support have been discussed.…”