Palladium-Catalyzed One-Pot Synthesis of Quinazolinones via tert-Butyl Isocyanide Insertion

Abstract

A novel palladium-catalyzed three-component reaction for the synthesis of quinazolin-4(3H)-ones from readily available 2-aminobenzamides and aryl halides via a palladium-catalyzed isocyanide insertion/cyclization sequence has been developed. This methodology efficiently constructs quinazolin-4(3H)-ones in moderate to excellent yields with the advantages of operational simplicity.

Quinazolinones from o‐Aminobenzonitriles by One‐Pot Sequential Selective Hydration/Condensation/Acceptorless Dehydrogenation Catalyzed by an Iridium Complex

“…2‐[4‐(Trifluoromethyl)phenyl]quinazolin‐4(3 H )‐one (5 ae) : White solid; 82 % yield (238 mg); m.p. 309–310 °C; 1 H NMR (500 MHz, [D 6 ]DMSO): δ =12.75 (br s, 1 H), 8.38 (d, J =8.2 Hz, 2 H), 8.18 (dd, J =1.2 Hz, J =8.0 Hz, 1 H), 7.93 (d, J =8.3 Hz, 2 H), 7.87 (t, J =7.7 Hz, 1 H), 7.79 (d, J =7.7 Hz, 1 H), 7.57 ppm (t, J =7.5 Hz, 1 H); 13 C { 1 H} NMR (125 MHz, [D 6 ]DMSO): δ =162.0, 151.1, 148.4, 136.6, 134.7, 131.1 (q, J C−F =32.1 Hz), 128.7, 127.6, 127.1, 125.8, 125.4 (q, J C−F =3.0 Hz), 123.9 (q, J C−F =272.3 Hz), 121.2 ppm.…”

“…2‐(Naphthalen‐2‐yl)quinazolin‐4(3 H )‐one (5 ao) : White solid; 87 % yield (236 mg); m.p. 276–277 °C; 1 H NMR (500 MHz, [D 6 ]DMSO): δ =12.67 (br s, 1 H), 8.82 (s, 1 H), 8.31 (d, J =8.4 Hz, 1 H), 8.19 (d, J =7.6 Hz, 1 H), 8.07 (t, J =7.1 Hz, 1 H), 8.01 (d, J =7.4 Hz, 1 H), 7.86 (t, J =7.3 Hz, 1 H), 7.80 (d, J =8.0 Hz, 1 H), 7.61–7.66 (m, 2 H), 7.54 ppm (t, J =7.3 Hz, 1 H); 13 C { 1 H} NMR (125 MHz, [D 6 ]DMSO): δ =162.2, 152.2, 148.8, 134.6, 134.1, 132.3, 129.9, 128.9, 128.1, 128.1, 127.9, 127.6, 127.5, 126.9, 126.6, 125.9, 124.5, 121.0 ppm.…”

Cyanation of Anilines to Aryl Nitriles Using tert‐Butyl Isocyanide: A Simple and Copper‐free Procedure

“…In particular, isocyanides were found to be a powerful precursors in the work of multicomponent reaction, namely the Passerine and Ugi reactions. In recent years, isocyanides have been used as a cyano source for the construction of C─O, C─C, C─N bonds and aldehydes through the insertion of isocyanides into C–X bonds via palladium‐catalyzed reactions . Herein, we would like to report on the use of tert ‐butyl isocyanide as cyano source for the conversion of anilines to aryl nitriles (Figure ).…”

Multicomponent reaction of benzyl halides: Synthesis of [1,2,4]triazolo/benzimidazolo quinazolinones

“…[20] Hence, the synthesis of quinazolinone has evoked much interest, as a result of which a variety of synthetic methodologies have been reported. [21][22][23] The most important approaches are (i) one-pot condensation of aromatic aldehydes, 2-amino benzimidazole/3-amino-1,2,4-triazole, and α-hydroxy C-H acids, [24] (ii) three-component reaction of 2-amino benzamides, aryl halides, and isocyanides, [25] (iii) one-pot reaction with o-amino benzamides and primary alcohols, [26] (iv) cascade synthesis of phenylamino substituted quinazolinones from urea derivatives and tert-butyl isocyanide, [27] [v] oxidative radical skeletal rearrangement induced by oxygen, [28] (vi) synthesis of quinazolinone and quinazoline from aerobic oxidative C(sp3)À H amination/ CÀ N cleavage. [29] Other methods have also been developed within the past three decades.…”