Synthesis of quinazolines and quinazolinones via palladium-mediated approach

Abstract

Quinazoline derivatives have drawn attention in the field of heterocyclic chemistry because of their unique skeleton and interesting biological applications. This review summarizes the recent palladium-catalyzed reactions used to construct quinazoline and its related 4(3 H )-quinazolinone analogues. The mechanisms of some Pd-catalyzed reactions are also discussed.

Bis(2-methoxyethyl)ether promoted intramolecular acceptorless dehydrogenative coupling to construct structurally diverse quinazolinones by molecular oxygen

“…Alkaloids containing a quinazolinone moiety widely exist in biologically active compounds 9 and natural products. 10 Although some approaches have been developed to prepare simple quinazolines, 11 efficient methods for the synthesis of structurally diverse dihydroisoquinolino[2,1- a ]quinazolinones are very limited. For example, Yan's group reported an iridium-catalysed intramolecular dehydrogenative coupling of tertiary amines and amides to access these compounds (Scheme 2a).…”

Highly Dispersed Single-Phase Ni2P Nanoparticles on N,P-Codoped Porous Carbon for Efficient Synthesis of N-Heterocycles

“…Given their extreme importance, various synthetic approaches have been developed for the synthesis of quinazolines, quinazolinones, and imidazoles over the past decades. Traditionally, oxidative condensation of diamines (or 2-aminobenzamides) with carbonyl compounds − ,− ,− or metal-catalyzed coupling of multicomponents ,− ,− ,− was frequently employed. However, these methods generally involved large excess of hazardous oxidants and suffered from limitations of substrate generality and availability of starting material, which strongly hamper their extensive application.…”

Base-Promoted Synthesis of 2-Aryl Quinazolines from 2-Aminobenzylamines in Water

“…Because of their great importance, a wide variety of synthetic methodologies − have been developed for the synthesis of quinazolines, including copper-catalyzed Ullman-type coupling followed by oxidation of o -bromobenzylamines or o -bromobenzyl (pseudo)­halides with amides or amidines (Scheme A) and the oxidative cyclization of arylamidines with one-carbon synthons, aldehyde equivalents, − or functionalized alkynes (Scheme B). Quinazolines can also be generated by the reaction of benzimidates with dioxazolones and the reaction of o -aminoaryl- or o -haloaryl carbonyl equivalents such as aldehydes, ketones, imines, and methanols with amines or amide equivalents such as nitriles or ammonia equivalents in the presence of carbon sources such as aldehydes and DMA (Scheme C).…”

“…These species can also be produced by condensation of o -aminobenzylamines with carbonyl equivalents such as aldehydes, ketones, alcohols, carboxylic acids, nitriles, or imine equivalents such as benzylamines or CO/ArBr (Scheme D). Despite the significant advancements, many of these methods suffer from one or several drawbacks such as harsh reaction conditions and the use of hazardous and/or expensive transition metal complexes, ligands, additives, base, oxidants, and solvents, which can lead to the production of hazardous waste and metal contamination of the final product. − Hence, the development of greener synthetic methodologies for the synthesis of quinazolines is still desirable. As a part of our continuing interest in the synthesis of valuable heteroaromatics, herein, we develop a sustainable methodology for the synthesis of 2-aryl quinazolines from easily available o -aminobenzylamines and α,α,α-trihalotoluenes by using only sodium hydroxide and molecular oxygen in water in the absence of any transition metal complex, ligand, chemical oxidant, or additive (Scheme E).…”