Chemoselective Cleavage of C(CO)−C Bond: Molecular Iodine‐Catalyzed Synthesis of Quinazolines through sp³ C−H Bond Functionalization of Aryl Methyl Ketones

Abstract

In this work, we report ac hemoselective C(CO)À Cbond cleavage of aryl methyl ketones in the presence of molecular iodine. The in situ generated keto aryl fragment combined with o-aminobenzyl amines to give quinzolines through aC ÀH/NÀHo xidativet andem cyclization.V arious derivatives of quinazolinesc ould be synthesized in good to excellent yields under transition-metal-and additivefree conditions.In recent years, the functionalization of C(sp 3 )ÀHb ond has come into sight as an ew and challenginga rea in organic chemistry. [1] Apart from methyl arenes, aryl methyl ketones are the one which has been explored prominently among the exampleso fC (sp 3 )ÀHc ontaining moieties. In the case of aryl methyl ketones, the functionalization of the C(sp 3 )ÀHb ond has been scrutinized in two ways (Scheme 1). First, extensively ex-Scheme1.Approaches for C(sp 3 )ÀHf unctionalization of aryl methylketones.

SeO2 Mediated Synthesis of Selected Heterocycles by Oxidative C−C Bond Cleavage of AcetophenoneDerivatives

“…On the basis of the experimental results and literature references, a plausible mechanism was proposed for the selenium dioxide formation of fused heterocycles (Scheme ). The acetophenone 1 formed Schiff's base with o‐phenylenediamine, which undergoes an intramolecular cyclization to give intermediate B .…”

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, 2017 , 2019 ; Raut 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 ; Donthiboina et al, 2020 ).…”

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).…”

“…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.…”

“…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).…”