Copper-Catalyzed Oxidative Multicomponent Annulation Reaction for Direct Synthesis of Quinazolinones via an Imine-Protection Strategy

Abstract

Via an imine-protection strategy, we herein present an unprecedented copper-catalyzed oxidative multicomponent annulation reaction for direct synthesis of quinazolinones. The construction of various products is achieved via formation of three C−N and one C− C bonds in conjunction with the benzylic functionalization. The merits of easily available feedstocks, naturally abundant catalyst, good functional group and substrate compatibility, and release of H 2 O as the byproduct make the developed chemistry a practical way to access quinazolinones.

Medicinal perspective of quinazolinone derivatives: Recent developments and structure–activity relationship studies

“…Route 13 demonstrates a copper‐catalyzed oxidative annulation scheme for synthesis of quinazolinone by treating substituted aniline with derivatives of amine and formaldehyde in the presence of copper catalyst (Cu(OTf) 2 ‐DTBP. The use of readily available substrates and catalyst, and harmless by‐products, make this scheme a practical way to develop quinazolinones [30]. Route 14 involves oxidative reaction of o ‐aminobenzamides and benzyl amines as the substrates.…”

Recent developments and perspectives in the copper-catalyzed multicomponent synthesis of heterocycles

“…An unprecedented synthesis of quinazolinones through an imine-protection method using copper( ii )-catalyzed oxidative multicomponent annulation was disclosed. 47 Primary amines, anilines and formaldehyde reacted to yield quinazolinones by the formation of one C–C bond and three C–N bonds along with benzylic functionalization ( Scheme 39 ). Optimization studies revealed that the use of Cu(OTf) 2 as well as DMSO (dimethyl sulfoxide) gave the best results in the reaction.…”

Selective Synthesis of 2-(1,2,3-Triazoyl) Quinazolinones through Copper-Catalyzed Multicomponent Reaction

“…A decrease in the reaction performance was observed at 80 °C instead of 100 °C, with product 5a being obtained in 60% yield (Table 1, entry 14). Notably, when higher temperatures were evaluated (120 and 140 °C), the formation of the aromatic quinazolin-4(3H)-one 6a was detected (Table 1, entries [15][16]. The overall yield refers to the mixture of compounds 5a and 6a as this cannot be separated by column chromatography.…”

“…Generally, the quinazolinones are synthesized by the condensation of o-aminobenzamides with aldehydes [10], phenylacetic acid [11] and alcohols [12,13]. Other important protocols include carbon-supported acid-catalyzed cascade coupling of isatoic anhydrides with amides and aldehydes [14], oxidative annulation of alcohols with o-aminoarylnitriles [15], and Cu-catalyzed oxidative annulation of anilines, alkylamines and aldehydes [16]. Recently, the use of copper catalysis in the synthesis of quinazolinones has received much attention.…”