Potassium Iodide‐Catalyzed Three‐Component Synthesis of 2‐Arylquinazolines via Amination of Benzylic CH Bonds of Methylarenes

Abstract

A novel potassium iodide-catalyzed three-component synthesis of quinazolines via benzylic C À H bonds amination was developed. Commonly used ammonia salt and the sp 3 carbon in commercially available methylarenes were used as nitrogen and C 1 sources, respectively. Mechanistic studies indicated that an aryl aldehyde is involved as a key intermediate in the reaction.

Palladium-Catalyzed Decarboxylative ortho-Acylation of Anilines with Carbamate as a Removable Directing Group

“…22 Furthermore, 6aa could react with NH 4 OAc and benzylic C–H bond of toluene to synthesize 2,4-diphenylquinazoline ( 7aa ) in 78% yield under the KI–TBHP conditions. 23 In addition, 6aa could be efficiently transformed to 2-methyl-4-phenylquinoline ( 8aa ) by reacting with acetone in 92% yield. 24…”

Silver‐Catalyzed Isocyanide Insertion into N−H Bond of Ammonia: [5+1] Annulation to Quinazoline Derivatives

“…Quinazoline derivatives are present in a wide variety of natural products and pharmaceuticals with significant physiological and biological activity . Thus, a large number of new synthetic strategies for their preparations have been developed to date . Among the existing methods, the direct assemble of quinazolines using NH 3 as nitrogen source attracted much attention.…”

“…In 2012, Wang and co‐workers developed an iodine‐catalyzed oxidative amination of C( sp 3 )‐H bonds for the synthesis of quinazolines from 2‐aminobenzophenones, ammonia, and N‐alkylamides (Scheme , eq 1, condition A) . Later, the three‐component reaction involving 2‐aminobenzophenones, aldehydes, and ammonium acetate for the direct access to quinazolines was independently reported by the research groups of Ma (Scheme , eq 1, condition B), Li (Scheme , eq 2), Zhang (Scheme , eq 3, condition A), Saha (Scheme , eq 3, condition B) . In addition, Wu and co‐worker reported a copper‐catalyzed cascade reaction of (2‐aminophenyl)methanols with aldehydes using the combination of cerium nitrate hexahydrate and ammonium chloride for the synthesis of quinazolines (Scheme , eq 4) .…”

Chemical Insights Into the Synthetic Chemistry of Quinazolines: Recent Advances

“…Li et al synthesized 2-arylquinazoline derivatives 41 through a three-component one-pot mild KI-promoted methodology under transition-metal-free conditions by the reaction of 2amino-benzophenones 28 with methylarenes 40 as one carbon source in the presence of NH 4 OAc (Zhao et al, 2015). The reaction demonstrated a wide spectrum of functional group tolerance including electron-deficient and electron-rich 2-aminoarylketones 28 and methylarenes 40 (Scheme 19).…”