tert-Butyl Hydroperoxide Promoted the Reaction of Quinazoline-3-oxides with Primary Amines Affording Quinazolin-4(3H)-ones

Abstract

An efficient and facile approach for the synthesis of quinazolin-4­(3H)-ones via the reaction of quinazoline-3-oxides with primary amines is described. This approach is demonstrated to be applicable for a broad range of substrates and proceeds efficiently under metal-free and mild reaction conditions employing easily available tert-butyl hydroperoxide as the oxidant. Remarkably, 3-(2-(1H-indol-3-yl) ethyl)­quinazolin-4­(3H)-one 3w, which was conveniently obtained by this process in 70% yield, was an excellent precursor for the synthesis of bioactive evodiamine and rutaempine.

Synthesis of Luotonin and Rutaecarpine Analogues by One‐Pot Intramolecular Dehydrogenative Cross‐Coupling and Benzylic C−H Oxidation, and In Vitro Cytotoxicity Assay

“…The key starting material 3‐benzyl quinazolin‐4( 3H )‐ones ( 5 a – 5 h ) has been synthesized in good yield by alkylation/benzylation at the N3 of quinazolinon‐4( 3H )‐one in the presence of K 2 CO 3 in acetone under refluxing condition, according to a reported protocol [25] (Scheme 2). The known [26] compound 5 k was synthesized by the alkylation of 3 b with 2‐bromomethyl naphthalene under similar conditions. The N 3‐alkylation was extended to synthesize compounds 5 i & 5 j [27] .…”

“…Copies of 1 H‐NMR, 13 C, HMBC, HSQC, HRMS, XRD data, and experimental details for compounds 5 , 6 and 7 are available in the Supporting Information section of this article. Additional references are cited within the Supporting Information [25–26,29] …”

Iodine-promoted amide formation via oxidative cleavage of indoles: novel quinazoline-4(3H)-one and tryptanthrin syntheses

“…The synthesis employed molecular oxygen and ammonium salts as O- and N-donors, respectively, together with a transition metal-free catalytic system of iodine. We aimed to develop a novel ‘green’ protocol to cleave a C 2 C 3 –H system for the formation of the C 2 –N–C 3 O combination to obtain quinazolin-4(3 H )-ones 9 and tryptanthrins 10 ( Scheme 1B ).…”