Synthesis of Substituted Quinazolin-4(3H)-imines From Aryldiazonium Salts, Nitriles and 2-Cyanoanilines via A Metal-Free Tandem Approach

Abstract

A transition metal-free synthesis of multisubstituted quinazolin-4(3H)-imines has been realized by the direct reaction of aryldiazonium salts, nitriles, and 2-cyanoanilines in a one-pot fashion. This strategy utilizes the in situ formation of reactive N-arylnitrilium intermediate, which undergoes further tandem cyclization with consecutive formation of N-C bonds. Broad functional group compatibility, mild conditions, shorter time, and operational simplicity are the notable features of this report.

Preparation of Ketimines from Aryldiazonium Salts, Arenes, and Nitriles via Intermolecular Arylation of N-Arylnitrilium Ions

“…In order to investigate the reactivity outcome of N -arylnitrilium intermediate, specific experiments were conducted (Scheme ). In contrast to our previous observations, aryldiazonium salt 6 reacted with 1,3,5-trimethoxy­benzene in acetonitrile to give 7 in excellent yield instead of the formation of 6-methyl­phenanthridine (Scheme a). Seemingly, the rate of intermolecular cyclization of N -arylnitrilium intermediate is much faster than that of the intramolecular pathway presumably due to the higher reactivity of the electron-rich arene component.…”

“…Due to their inherent electrophilicity, coming from N 2 being an excellent leaving group, aryldiazonium salts have been utilized in various transition-metal free organic transformations . In particular, the synthetic application involving in situ generation of a nitrilium ion from aryldiazonium and nitrile has received much attention due to the easy handling procedure. , Approaches for the multisubstituted phenanthridine core from 2-aryldiazonium salts and nitriles were documented via the in situ generation of the N -arylnitrilium intermediate followed by intramolecular arylation (Scheme A). , Inspired by this work and our recent developments on aryldiazonium salts based applications, − herein, we disclose a mild and transition-metal-free synthesis of N -arylketimines, involving the reaction of the reactive N -arylnitrilium intermediate with activated aryl compounds via an intermolecular fashion (Scheme B) …”

Copper‐Promoted Tandem Three‐Component Access to Quinazolin‐4(H)‐imines and Benzimidazo[1,2‐c]quinazolines

“…An alternative three‐component process, based on a Pd‐catalyzed isocyanide insertion onto a haloaryl carbodiimide in the presence of an amine, was also described to afford 2‐amino quinazolin‐alkylimines (Scheme b) . Recently, the metal free multicomponent reaction between anthranilonitriles, aryldiazonium salts and nitrilated solvents was reported to deliver quinazolinimines (Scheme c) . In addition to these truly three‐component reactions, (2 C+1 C) component processes, involving two equivalents of one reagent, have also appeared .…”

Copper‐Catalyzed Three‐Component Cascade Reaction of Benzaldehyde with Benzylamine and Hydroxylamine or Aniline: Synthesis of 1,2,4‐Oxadiazoles and Quinazolines

“…Meanwhile, the general synthesis procedure for quinazoline is the condensing of different ortho ‐functionalized anilines (2‐carbonylaniline, [10a,b,c,d] 2‐aminobenzylamine [10e,f] or 2‐aminobenzonitrile [10g,h] ) with benzaldehyde, benzylamine, benzoic acid or benzonitrile (Scheme 1 b). Moreover, another feasible method is the oxidative cyclization of arylamidines with I 2 ‐mediated C−C bond, and the later one was formatted from C( sp 3 )−H and C( sp 2 )−H bonds [11] .…”