Synthesis of quinazolines from 2-aminobenzylamines with benzylamines and N-substituted benzylamines under transition metal-free conditions

Abstract

This work reports the synthesis of quinazolines from 2-aminobenzylamines with N-substituted benzylamines in the presence of molecular iodine. The developed methodology works smoothly under transition-metal free, additive free and solvent free conditions. The use of O as a green oxidant makes it a greatly economical, green and sustainable protocol. Moreover, no aqueous work up is required thereby enhancing the efficiency. A series of quinazoline derivatives were synthesized successfully in good to excellent yields.

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

“…Herein, we wish to report a direct tandem cyclization of aryl methyl ketones with o ‐aminobenzyl amines by the C−H/N−H oxidative coupling involving a direct C(sp 3 )−H bond oxidation amination through the C(CO)−C bond cleavage (Scheme ). Unlike our previous report, there is no use of excess of toxic starting materials, thereby making this approach more green for the preparation of quinazolines.…”

“…Recently, we reported a new protocol, which overcomes the limitations of the above methodologies, for the synthesis of quinazolines using benzyl amines as aryl precursors in the presence of molecular iodine . It is still interesting to report another synthetic protocol with different challenging chemistry i.e.…”

Iridium-Catalyzed Acceptorless Dehydrogenative Coupling of 2-Aminoarylmethanols with Amides or Nitriles to Synthesize Quinazolines

“…43, 159.34, 149.48, 141.27, 137.54, 134.89, 130.38, 129.49, 129.23, 128.57, 124.40, 120.45, 21.56. 6,8-Dibromo-2-(4-methoxyphenyl)quinazoline (3de) 26 Yellow solid; mp 176-177 °C; yield: 348.8 mg (89%).…”

Metal-Free Synthesis of 2-Substituted Quinazolines via Green Oxidation of o-Aminobenzylamines: Practical Construction of N-Containing Heterocycles Based on a Salicylic Acid-Catalyzed Oxidation System

“…From the viewpoint of green chemistry, the development an eco-friendly synthesis method for quinazolines with excellent environmental factor (E-factor (%) = kg waste/kg product) and reaction mass efficiency (RME (%) = kg product/kg all reactants × 100) remains challenging (see the Supplementary Information , Han et al, 2011 ; Saha et al, 2017 ; Yamaguchi et al, 2016 ; Yamaguchi et al, 2017 ; Gujjarappa et al, 2018 .). The availability of quinazolines for large-scale synthesis under metal-free conditions is also an important factor in pharmaceutical and industrial chemistry; however, previous methods achieved synthesis only up to the 1 mmol scale ( Tiwari and Bhanage, 2016 ; Gopalaiah, et al, 2017 ; Deshmukh and Bhanage, 2018 ). Thus, it is imperative to develop a practical synthesis method that can be implemented on a larger scale and offers excellent E-factor and RME.…”