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

Abstract

A transition-metal-free procedure for the synthesis of a highly valuable class of heteroaromatics, quinazolines, was developed by using easily available 2-aminobenzylamines and α,α,α-trihalotoluenes. The transformation proceeded smoothly in the presence of only sodium hydroxide and molecular oxygen in water at 100 °C, furnishing a variety of 2-aryl quinazolines. The crystallization process of the crude reaction mixture for the purification of the solid products circumvents huge solvent-consuming workup and column chromatographic techniques, which make the overall process more sustainable and economical.

Synthesis of Quinazoline and Quinazolinone Derivatives via Ligand-Promoted Ruthenium-Catalyzed Dehydrogenative and Deaminative Coupling Reaction of 2-Aminophenyl Ketones and 2-Aminobenzamides with Amines

“…(9) Cho and co-workers recently devised a practical synthesis of 2-arylquinazoline derivatives from the coupling of 2-aminobezylamines with halogenated toluene substrates. (10) Since the advent of the Niementowski condensation of anthranilic acids with amides,(11) a variety of sustainable synthetic methods have also been devised for the assembly of quinazolinone core structures. (12) Much recent research effort has been devoted to the development of catalytic coupling methods to increase efficiency and selectivity in constructing quinazolinone core structures.…”

Hydrogen peroxide-mediated synthesis of 2,4-substituted quinazolines via one-pot three-component reactions under metal-free conditions

“…These observations conrmed the essential role of active oxygen species for the transformation. Based on experimental observations and previous reports, 6,12,15 the proposed pathway for the formation of quinazoline derivatives was shown in Scheme 3. Firstly, ammonium acetate was decomposed to NH 3 and AcOH by heating.…”

“…[1][2][3][4] Due to their pharmaceutical applications and signicant biological value, a variety of methodologies have been explored for the synthesis of these structures. Typical approaches started from ortho-functionalized anilines and derivatives, such as 2-carbonyl anilines, 5 2-aminobenzylamines, 6 and 2-aminobenzonitriles. 7 Recently, several new strategies from diversied starting materials using transition metal catalysts have been developed for the construction of substituted quinazolines.…”

Niacin as a Potent Organocatalyst towards the Synthesis of Quinazolines Using Nitriles as C–N Source

“…General Method: The starting material 2‐amino‐4‐methylbenzylamine ( 1b ) was prepared using previously reported method and all other starting materials were purchased from commercial suppliers (Sigma‐Aldrich, Alfa‐Aesar, SD fine chemicals, Merck, HI Media, Ambinter) and were used without further purification unless otherwise indicated. All reactions were performed in a 10 mL reaction vial with magnetic stirring.…”