One Pot Synthesis of 4(3H)‐Quinazolinones

Abstract

Anthranilamides undergo cyclocondensation with aldehydes in presence of iodine in a single‐pot reaction to afford 2‐substituted 4(3H)‐quinazolinones in moderate to excellent yield (40–95%). 2,3‐Substituted 4(3H)‐quinazolinones are synthesized in moderate to good yield by three‐component condensation of isotoic anhydride, amine, and aldehyde in presence of iodine.

^#CDRI communication no. 6374.

Keywords:

• 4(3H)‐Quinazolinones
• Iodine
• Three‐component reaction
• One pot synthesis

Notes

^#CDRI communication no. 6374.

^aTypical example: to a solution of anthranilamide 6 (R³ = H, 5 mmol) dissolved in 20 mL of anhydrous DMF, 3,4,5‐trimethoxybenzaldehyde (5 mmol) is added. To the resulting mixture while stirring, iodine (6 mmol) and anhydrous potassium carbonate (5 mmol) are added and then heated at 60–80°C for 6 hr. The mixture is poured into crushed ice‐water in (200 mL). The precipitated product is filtered, washed with water, and then recrystallized from alcohol. IR (KBr): 3442, 2935, 1673, 1605, 1457 cm⁻¹; ¹H NMR (200 MHz, CDCl₃) (ppm): 3.71 (s, 3H), 3.73 (s, 3H), 3.87 (s, 3H), 7.24–7.34 (m, 3H), 7.59–7.61 (m, 2H), 8.06 (bs, 1H), FAB mass: m/z 213 (M⁺ + 1, 100%), 154, 136.

^b2,3‐Dihydro 4(3H)‐quinazolinones have been synthesized in moderate yield from isotoic anhydride and aromatic aldimines under drastic conditions.

^cTypical example: to a solution of isotoic anhydride (1 mmol) dissolved in 5 mL of anhydrous DMF, N‐butyl amine (1 mmol) and benzaldehyde (2 mmol) are added. The resulting mixture is while stirring; iodine (1.2 mmol) and powdered KOH (1.2 mmol) are added and then heated at 60–80°C for 8 hr. The product mixture is diluted with crushed ice‐water and extracted with ethyl acetate. After usual work‐up, liquid product is purified by silica gel chromatography and recrystallized from alcohol to obtain 1k. IR (KBr): 1662, 1605, 1457 cm⁻¹; ¹H NMR (200 MHz, CDCl₃) (ppm): 0.83 (t, 3H), 1.42 (m, 4H), 3.86 (m, 3H), 7.43 (s, 5H), 7.44–93 (m, 4H), FAB mass: m/z 279 (M⁺ + 1).