Preparation of Quinazolines via a 2+2+2 Annulation from Aryldiazonium Salts and Nitriles

Abstract

A (2+2+2) modular synthesis of multisubstituted quinazolines has been realized by the direct reaction of aryldiazonium salts with two equivalent of nitriles. Reaction of aryldiazonium salt with a nitrile provides the initial formation of a reactive nitrilium ion, which is attacked by another molecule of nitrile followed by electrophilic cyclization to deliver the desired product. Notable flexibility in the substitution patterns, readily available substrates, short reaction time, transition metal-free, and gram-scale synthesis are the advantages of this method.

Preparation of 3-hydroxyquinolines from direct oxidation of dihydroquinolinium salts

“…Interestingly, when arylnitrile was employed, the corresponding 2,4-diaryl substituted quinolinium salt (3h) was obtained as the major products, but accompanied with quinazolines (4) as the side product ( Scheme 2 ). 18 c Similarly, when α-methylstyrene was used as the substrate, a 4,4-disubstituted dihydroquinoline 3m was isolated in 49% yield. However, reaction of α-bromostyrene with 1a in acetonitrile gave quinoline 5 as the single product presumably due the elimination of HBr ( Scheme 3 ).…”

“…When aryldiazonium salt bearing adjacent phenyl or methylthio moiety was employed, N -arylnitrilium intermediate expeditiously underwent the intramolecular cyclization to deliver 6-methyl-phenanthridine 18 (8) and 2-substituted benzothiazole (9) ( Scheme 7 ). Presumably, the intra-molecular pathway is superior to the inter-molecular one.…”

Synthesis of acylnaphthylamines and their applications in the formation of benzoquinazolines

“…38 However, there are few examples of the synthesis of benzoquinazoline systems with simple alkyl substituents. 38,40,41 In this work alkylbenzoquinazoline derivatives were synthesized by the thermal condensation (170 °C) of (acylnaphthyl)carbamates 2a,b, 18 or their derivatives 15a, 19 with HCONH2/AcONH4 (Scheme 4). Transformation of aminoketones 15a, 19 provided the desired products 16a, 20 in moderate yields (35%, 30%, respectively).…”

Microwave-Assisted Synthesis of Quinazolines and Quinazolinones: An Overview

“…Although the aforementioned reactions are considered as the most important transition-metal catalyses, a plethora of vital reactions can be effectively catalyzed by various transition metals including reductive elimination, oxidative addition, and transmetallation. Transition metal catalysis has also found extensive applications in the convenient and efficient synthesis of a wide variety of heterocyclic systems (Ma et al, 2017;Ramanathan and Liu, 2017;Tiwari and Bhanage, 2017;Chatterjee et al, 2018;Saikia et al, 2018;Chen et al, 2020;Debabrata et al, 2020;Ghosh et al, 2020;Janardhanan et al, 2020;Jiang et al, 2020;Kanwal et al, 2020;Kojima and Matsunaga, 2020;Li and Zhang, 2020;Nagata and Obora, 2020;Neto and Zeni, 2020a,b;Pal et al, 2020;Ratmanova et al, 2020;Sahiba and Agarwal, 2020;Sonawane et al, 2020;Xuan et al, 2020). However, the literature survey revealed only an example of zinc (Shi et al, 2004), a limited number of iron-catalyzed (Melvin et al, 1992;Valderrama et al, 1999;Kanth et al, 2006;Yin et al, 2012;Gopalaiah et al, 2017Gopalaiah et al, , 2019Raut and Bhanage, 2017;Eidi et al, 2018), and relatively more copper-catalyzed reactions, leading to the synthesis of quinazoline and quinazolinone derivatives (Melvin et al, 1992;Chatterjee et al, 2018;Potuganti et al, 2018;Liang et al, 2019;Rodrigues et al, 2019;Donthibo...…”