DMSO as C1 Source under Metal‐ and Oxidant‐free Conditions: NH₄SCN‐mediated Synthesis of Quinazolinone and Dihydroquinazolin‐4(1H)‐one Derivatives

Abstract

A new and efficient strategy for the development of quinazolinones and dihydroquinazolin-4(1H)-ones promoted by ammonium thiocyanate is reported. Most remarkably, dimethyl sulfoxide is used for solvent as well as methine and bridged methylene source to obtain a wide variety of new N, N-disubstituted 2,3-dihydroquinazolin-4(1H)-ones. This transformation possesses significant advantages such as metal-and oxidant-free, non-acidic medium, simple condition, good functional group tolerance and broad substrate scope. Besides, this process could be readily scaled up and applied to drug molecules synthesis.

Iodine-Promoted Oxidative Cyclization of Acylated and Alkylated Derivatives from Epoxides toward the Synthesis of Aza Heterocycles

“…Recently, our group reported a technique using DMSO that serves as the −CH 2 and −CH synthon to produce quinazoline derivatives (Figure 1c). 18 As a continuation of our efforts toward the construction of N-heterocycles, 19 we herein developed a fast and efficient method for producing biologically active diverse N-heterocycles such as 2-benzoylquinazolin-4(3H)-one and phenyl-(pyrrolo[1,2-a] quinoxalin-4-yl) methanone derivatives using epoxides as acyl precursors (Figure 1d). In addition, the same approach could also be used to successfully synthesize a range of novel 1-methyl-dihydroquinazolin-4(1H)-ones in batch, and the use of continuous flow reaction conditions allowed the reduction of the reaction time, made it operationally safe, and improved the reaction yields over the batch technique.…”

“…Considering the synthetic importance, the evolution of a simple, transition-metal-free, and single protocol for diverse methods allowing effective access to this class of aza heterocycles would be highly desirable. Recently, our group reported a technique using DMSO that serves as the −CH 2 and −CH synthon to produce quinazoline derivatives (Figure c) . As a continuation of our efforts toward the construction of N -heterocycles, we herein developed a fast and efficient method for producing biologically active diverse N -heterocycles such as 2-benzoylquinazolin-4­(3 H )-one and phenyl­(pyrrolo­[1,2- a ] quinoxalin-4-yl) methanone derivatives using epoxides as acyl precursors (Figure d).…”