Temperature-controlled synthesis of N-acyl anthranilamides and quinazoline-4-ones via Pd-catalysed cascade consisting of isocyanide insertion

Abstract

A one step synthesis of functionlized N-acyl anthranilamide via Pd-catalyzed carboxamidation of o-halo substituted N-phenylamide consisting of isocyanide insertion followed by oxidation of the imine intermediate has been achived successfully. Furthermore, at elevated temprature (160 o C) the Pd-catalyzed tandem reaction afforded functionlized quinazolin-4-one in a single step without the isolation of N-acyl anthranilamide and proceed through carboxamidation/de-t-butylation/cyclodehydration cascade. This work extends the application of isocyanide insertion chemistry for synthesizing diverse N-heterocycles by transition metal catalysed sequential reactions in a single step.

Recent Advances in Palladium-Catalyzed Isocyanide Insertions

“…A related method affords 2-substituted (3 H )quinazolin-4-ones from N -acyl 2-bromoanilines 64 . [ 44 ] This method relies on the direct hydroxyimidoylation of the aryl halides with water as the nucleophile, affording bisamides 65 at 120 °C from either tert -butyl isocyanide or cyclohexyl isocyanide ( Scheme 20 ). If the temperature is raised to 160 °C, the generated bisamide undergoes a cyclocondensation to quinolinones 66 , which is accompanied by spontaneous de- tert -butylation.…”

Transition Metal and Inner Transition Metal Catalyzed Amide Derivatives Formation through Isocyanide Chemistry

“…103 Khan, Tyagi, and co-workers reported a temperaturecontrolled synthesis of N-acylanthranilamide 140 and quinazolin-4-one 141 (Table 1). 104 N-(2-Bromophenyl)benzamide (139) reacted with tert-butyl isocyanide in the presence of Pd(OAc) 2 under microwave (MW) conditions at 120 °C to yield 2-benzamido-N-tert-butylbenzamide (140) via carboxamidation. By elevating the temperature to 160 °C under the same conditions, 2phenylquinazolin-4(3H)-one (141) was formed as the sole product through a carboxamidation/de-tert-butylation/cyclodehydration cascade.…”

“…Sc(OTf) 3 -catalyzed tandem conjugate addition of isocyanides to 4-oxo-4H-chromene-3-carboxylic acid(104) under microwave conditions in THF/H 2 O gave 4-oxochromane-2carboxamides 105 (Scheme 35) 90. Moreover, the reaction in toluene and a small amount of alcohol at 60 °C in the presence of Sc(OTf) 3 gave 2-carbamoyl-4-oxochromane-3-carboxylates 106.…”