Synthesis of novel azole-fused quinazolines via one-pot, sequential Ullmann-type coupling and intramolecular dehydrogenative C–N bonding

Abstract

An efficient one-pot sequential procedure is described for the synthesis of novel azole-fused quinazolines through Pd/Cu co-catalyzed, Ullmann-type coupling followed by cross dehydrogenative coupling of various azoles such as 1H-imidazole, 1H-benzimidazole and 1H-1,2,4-triazole with 2-(2-bromophenyl)-1H-imidazole/benzimidazoles. The developed strategy has offered good yields (52-81%) of diverse N-fused tetra-, penta- and hexa-cyclic frameworks in a single step.

One-Pot NBS-Promoted Synthesis of Imidazoles and Thiazoles from Ethylarenes in Water

“…As a result, α,α-dibromoethybenzene ( 1ab ) and acetophenone ( 1ac ) could also be converted into 3a using the present reaction procedure and conditions, which contributes to improve the yield of this reaction. On the basis of mechanistic experiments and a literature survey [24,40], a plausible pathway for the reaction has been proposed, as shown in Scheme 4, taking the reaction of ethylbenzene ( 1a ) and 2-aminopyridine ( 2a ) for the synthesis of imidazo[1,2-a]pyridine ( 3a ) as an example. α-Bromoethybenzene is formed in the reaction of ethylbenzene ( 1a ) with bromine atoms formed from NBS (Wohl-Ziegler reaction) [41].…”

“…These compounds exhibit a plethora of biological properties displayed over a broad range of therapeutic classes, including antibacterial, antifungal, antiviral, antiulcer, anti-inflammatory, β-amyloid formation inhibitory, immunosuppressive, GABA receptor agonist, cardiotonic agent, and nonpeptide B 2 receptor antagonist effects [17,18,19,20,21]. Various synthetic methods have been reported for the construction of these motifs such as C-H amination, oxidative cyclization, multi-component reaction, hydroamination, and tandem processes from various starting materials [22,23,24,25,26]. Traditionally, procedures for these reactions required the use of metals and catalysts in various organic solvents, which makes the sequence longer and increases waste production.…”

Aldo‐X Bifunctional Building Blocks for the Synthesis of Heterocycles

“…Many important heterocycle scaffolds have also been constructed through two‐step reactions from o ‐halogen‐substituted benzaldehydes . The construction of a precursor that is amenable to a cyclization reaction through intra‐ or intermolecular C–C or C–N bond formation, with or without counter‐reagent, is the key to making such a two‐step reaction possible …”

A series of (E)-5-(arylideneamino)-1-tert-butyl-1H-pyrrole-3-carbonitriles and their reduction products to secondary amines: syntheses and X-ray structural studies

“…Furthermore, N-substituted 5-aminopyrazole is a versatile 1,3-C,N-bis-nucleophilic building block for synthesizing diverse functionalized bis-azaheterocycles (Quiroga et al, 2007;Portilla et al, 2012;Castillo et al, 2016Castillo et al, , 2017. Interestingly, heterocyclic compounds derived from the fusion of azoles with six-membered unsaturated heterocycles have remained unexplored (Lin et al, 2014;Nandwana et al, 2015). In this context (see Schemes 2 and 3), we recently reported the thermal condensation reactions between N-substituted 5-aminopyrazole (1) and diverse (hetero)aromatic aldehydes to afford pyrazole-imines (3), which are the first intermediates isolated in an efficient and selective three-step procedure for the synthesis of pyrazoloxazines (5) in high yields (Scheme 2).…”