Copper‐Catalyzed Synthesis of Quinazolines in Water Starting from o‐Bromobenzylbromides and Benzamidines

Abstract

Water makes it possible: The Cu(2)O-catalyzed reaction between easily available o-bromobenzylbromides and benzamidines by using Cs(2)CO(3) as the base and N,N'-dimethylethylenediamine (DMEDA) as the additive in water as the solvent gives access to substituted quinazolines in a single step with yields ranging from 57 to 85 % (see scheme).

C−N Cross‐Coupling Reactions Under Mild Conditions Using Singlet Di‐Radical Nickel(II)‐Complexes as Catalyst: N‐Arylation and Quinazoline Synthesis

“…To further explore the potential of our methodology, we investigated the reaction of 2-bromobenzylamine (9 b) with various amidines (11 a-i), which is one of the key functional group in modern drug synthesis to construct various N-heterocycles including quinazolines. [19] To our satisfaction, catalyst 3 proved to be efficient in the CÀ N cross-coupling of benzami-…”

“…Moreover, our synthetic protocol has also been found suitable for the synthesis of six member N-heterocycles (quinazolines) via CÀ N cross-coupling of benzamides and amidines with 2-bromobenzylamine and 2-bromobenzylbromide respectively, under relatively mild reaction conditions. [18,19] It is worth mentioning that quinazolines are common building blocks for numerous alkaloids and functional molecules displaying a broad range of biological and therapeutic activities. [20] Consequently, over the years the synthesis of quinazolines has attracted significant attention.…”

Expanding applications of zeolite imidazolate frameworks in catalysis: synthesis of quinazolines using ZIF-67 as an efficient heterogeneous catalyst

“…Initial studies addressed the effect of temperatures on the conversion of 2-aminoacetophenone to 2-phenylquinazoline. 2,7,49,50 Scheme 1 Cyclization reaction of 2-aminoacetophenone and benzylamine using ZIF-67 catalyst. It was observed that the cyclization reaction could not occur at room temperature, with no trace amount of product aer 180 min.…”

One-Pot Tandem Synthesis of 2-Arylquinazolines by a Multicomponent Cyclization Reaction

“…No reaction occurred when the procedure was carried out in the absence of copper catalyst (Table 1, entry 18). Finally, we studied the solvent effect and found that CH 3 CN was superior to toluene, THF, PhCl, and DMF (Table 1, entries 12,[19][20][21][22]. In addition, the reaction failed to give the desired product when the procedure was carried out under a N 2 atmosphere.…”

“…Zhang reported a three-component synthesis of quinazoline derivatives using a low melting sugar-urea-salt mixture as a solvent [19]. In 2012, Beifuss and co-workers developed a copper-catalyzed coupling reaction of o-bromobenzylbromides and benzamidines for the synthesis of quinazolines in an aqueous medium [20]. The condensation reactions of 2-aminobenzylamines with aldehydes followed by subsequent oxidation with strong oxidants (e.g., 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ) [21], MnO 2 [22], and NaClO [23]) provide a conventional but simple method to synthesize quinazolines (Scheme 1(a)).…”