Novel Annulation of Cyanuric Chloride with 2‐Aminobenzamides: A New Approach to 2‐Amino‐3‐substituted Quinazolin‐4(3H)‐ones

Abstract

A simple and efficient method for preparation of 2-amino-3substituted quinazolin-4(3H)-ones by reaction of cyanuric chloride with 2-amino N-substituted benzamides in acetonitrile-water (2 : 1) using sodium bicarbonate as a mild base is described. Using this metal-free method, a variety of 2amino-3-substituted quinazolin-4(3H)-ones were obtained in good to excellent yields. Here, both organic and inorganic bases were found to promote this reaction and the best results were observed with sodium bicarbonate. This study is the first observation of cyanuric chloride to act as a source for creation of amine functionality in 2-amino-3-substituted quinazolin-4(3H)-ones.

Pyridyl Glycosyl Triazole/CuI-Mediated Domino/Tandem Synthesis of Quinazolinones

“…analysis. The obtained data were found in close agreement with the literature . The designed tandem reaction takes place efficiently with 10 mol % of Cu­(I) iodide and 5 mol % of L1 , on further increasing the catalytic loading did not change the yield significantly, while 5 mol % of CuI with 5 mol % of L1 afforded excellent yields of 7a using N -benzyl-2-iodobenzamide at 110 °C (Table , entries 20–21).…”

“…The obtained data were found in close agreement with the literature. 36 The designed tandem reaction takes place efficiently with 10 mol % of Cu(I) iodide and 5 mol % of L1, on further increasing the catalytic loading did not change the yield significantly, while 5 mol % of CuI with 5 mol % of L1 afforded excellent yields of 7a using N-benzyl-2iodobenzamide at 110 °C (Table 1, entries 20−21). The devised protocol for the synthesis of 2-amino-3-benzylquinazolin-4(3H)-one (7a) from N-benzyl-2-bromobenzamide (6a) and cyanamide showed an excellent conversion with the optimized tandem condition, that is, 10 mol % of copper(I) iodide, 5 mol % of pyridyl glycosyl triazole L1, and 1.2 equiv.…”

“…2-Amino-3-benzylquinazolin-4(3H)-one (7a). 36 White crystalline solid, yield 118 mg (92%); R f = 0. 2-Amino-3-phenylquinazolin-4(3H)-one (7b).…”

“…2-Amino-3-benzylquinazolin-4(3H)-one (7a). 36 White crystalline solid, yield 118 mg (92%); R f = 0.42 (60% EtOAc/n-hexane); mp = 198−200 °C; 1 H NMR (500 MHz, DMSO-d 6 ): δ 7.91 (d, J = 8.0 Hz, 1H), 7.58−7.56 (m, 1H), 7.32−7.29 (m, 2H), 7.25−7.18 (m, 4H), 7.10 (t, J = 7.5 Hz, 1H), 6.97 (s, 2H) 5.27 (s, 2H); 13 C{1H} NMR (125 MHz, DMSO-d 6 ): δ 162. 5, 152.4, 150.3, 136.8, 134.8, 128.9, 127.6, 127.2, 127.1, 124.3, 122.0, 116.5, and 44.3 ppm.…”

“…The diverse biological activities of quinazolinones have led to the need of a novel efficient catalytic system for an appropriate chemical transformation to render these bioactive quinazolinones under easy-going reaction conditions. Several synthetic approaches have been reported for the synthesis of quinazolinones using different types of starting substrates. − A classical method for the synthesis of quinazolinones involves a condensation reaction of anthranilic acid and its derivative with formamide synthons. − However, this approach suffers from low yields, multistep reaction, and harsh reaction conditions. In addition to the classical method, the ligand-assisted transition-metal-catalyzed Ullmann coupling reaction followed by cyclization is a well known and proficient method to assemble these derivatives. − Various conventional and new ligands have been reported, which stabilized the oxidation states of Cu during the coupling reaction. − A major breakthrough for the synthesis of quinazolinones was independently reported by the Ding and Fu Group via a domino reaction under mild Cu-catalyzed conditions starting from N -substituted o -halobenzamides and o -halobenzoic acids. , Furthermore, the Ma group developed a facile and efficient approach to assemble these derivatives via the Cu­(I)/-4-hydroxy- l -proline-catalyzed aryl amidation reactions .…”