Simple and straight forward synthesis of 2,4-disubstituted quinazolines in aqueous medium

Abstract

KEYWORDSEfficient synthesis of diverse quinazolines from readily available starting materials was achieved in aqueous medium via one-pot protocol. A number of 2,4-disubstituted quinazolines were prepared in moderate to good yields under mild and catalyst-free conditions. Neutral reaction conditions, easy work-up procedures with wide substrate scope and atom economy are the remarkable features of this method.Catalyst free Aqueous medium One-pot synthesis Ammonium acetate 2-Amino carbonyl compounds 2,4-Disubstituted quinazolines

An Efficient Three‐component, One‐pot Synthesis of Quinazolines under Solvent‐free and Catalyst‐free Condition

“…The structures of the products were unequivocally confirmed by spectral data and elemental analysis. All spectra of previously reported compounds were consistent with literature .…”

“…However, this method requires tedious synthesis of starting materials. Recently, Bandaru et al synthesized 2,4‐disubstituted quinazolines in aqueous medium using 2‐aminocarbonyl compounds, aldehydes, and ammonium acetate; however, this method has limitations such as its low product yield, the requirement of excess ammonium acetate (10 equiv), and failure to yield the required product with aliphatic aldehydes. The three‐component synthesis of quinazolines using molecular iodine catalyst under neat/EtOH condition and copper‐catalyzed traditional solvent‐assisted synthesis were reported during the course of the present work.…”

Nickel‐catalyzed Kumada Cross‐coupling Reaction for the Synthesis of 2,4‐Diarylquinazolines

“…5, 21.6, 121.7, 126.7, 127.1, 128.7, 129.1, 129.3, 129.4, 130.2, 133.4, 134.9, 135.6, 140.1, 140.7, 152.0, 160.3, 168 5, 55.5, 114.0, 121.6, 126.6, 127.1, 128.6, 129.1, 129.3, 130.3, 131.9, 133.3, 135.6, 140.6, 152.1, 160.3, 161.2, 167.6 4-(4-Fluorophenyl)-2-phenyl quinazoline (3p) [12]. This compound was obtained as a white solid, yield 46.9 mg (78%), mp 144-146°C; J C-F =20.0Hz), 121.6, 126.7, 127.1, 128.6, 128.8, 129.3, 130.6, 132 121.6, 124.6, 126.0, 126.1, 127.5, 127.7, 128.0, 128.2, 128.6, 129.5, 129.7, 132.7, 135.4, 135.9, 137.2, 150.4, 159.3, 168.8 20.5, 121.5, 124.6, 125.8, 126.0, 127.7, 127.9, 128.1, 128.3, 128.6, 129.7, 132.6, 134.5, 135.5, 135.9, 139.7, 150.5, 159.3, 168.7 2H),2H),8.11 (d,J = 8.4 Hz,1H),8.48 (d,J = 8.4 Hz,1H),8.57 (d,J = 8.0 Hz,2H);13 C NMR (100 MHz, CDCl 3 ): δ 21. 6,120.5,126.0,127.2,128.1,128.2,128.5,129.4,130.4,131.0,133.5,135.2,140.8,142.1,152.5,160.1,160.3;HRMS (ESI) 6, 126.0, 127.4, 128.2, 128.6, 129.4, 130.4, 130.5, 130.6, 131.1, 133.6, 137.9, 142.0, 152.5, 160.0, 160.4 1, 119.9, 126.7, 128.1, 128.2, 128.5, 128.7, 129.2, 129.3, 129.9, 130.2, 137.9, 138.4, 144.5, 152.3, 160.4, 167.8 5, 21.1, 118.7, 125.7, 126.9, 127.4, 127.5, 128.0, 128.2, 128.8, 129.1, 134.5, 136.8, 139.6, 143.4, 151.2, 159.4, 166.7 4, 20.5, 21.1, 118....…”

“…This compound was obtained as a white solid, yield 61.6 mg (88%), mp 123-126°C; 1 H NMR (400 MHz, CDCl 3 ): δ 7.60-7.62 (m, 4H), 7.76-7.78 (m, 2H), 7.88-7.94 (m, 3H), 8.17 (t, J = 7.6 Hz, 2H), 8.81 (d, J = 8.0 Hz, 2H); 13 C NMR (100 MHz, CDCl 3 ): δ 120.9, 121.9, 124. 4, 126.1, 126.6, 127.6, 127.9, 128.2, 129.1, 131.5 (q, J C-F = 32.0 Hz), 132.8, 136.3, 140.5, 150.8, 157.7, 167.5 4, 121.6, 127.1, 127.2, 128.5, 128.6, 128.9, 130.1, 133.9, 137.2, 145.4, 151.5, 152.8, 153.5, 168.9 4, 120.6, 125.8, 126.0, 127.5, 127.7, 128.1, 128.2, 129.2, 129.4, 132.4, 133.8, 137.2, 139.1, 150.9, 159.2, 167.2.…”