Recyclable Palladium-Catalyzed Carbonylative Coupling of 2-Iodoanilines, Trimethyl Orthoformate, and Amines: A Practical Synthesis of Quinazolin-4(3H)-ones

Abstract

An efficient heterogeneous palladium-catalyzed carbonylative annulation of 2-iodoanilines, trimethyl orthoformate, and amines has been developed. The reaction proceeds smoothly in toluene at 110 °C using N,N-diisopropylethylamine (DiPEA) as base and 2 mol% of MCM-41-anchored bidentate phosphine palladium complex [MCM-41-2P-Pd(OAc)2] as catalyst under 10 bar of carbon monoxide and provides a general and practical method for the construction of a wide variety of quinazolin-4(3H)-ones in good to excellent yields from commercially easily available starting materials. This heterogenized palladium catalyst can be easily recovered via a simple centrifugation process and reused more than nine times with almost consistent catalytic efficiency.

Synthesis of quinazolinonesviaCp*Co(iii)-catalyzed C–H functionalization of primary amides with oxadiazolones

“…Among them, the 4(3 H )-quinazolinone skeleton 2 is an important and privileged scaffold in medicinal chemistry; for instance, methaqualone 3 exhibits significant anticonvulsant activity; (−)-vasicinone 4 exhibits antitumor, bronchodilating, hypotensive, anthelmintic, and antianaphylactic activities; luotonin A 5 is a potential antitumor agent; and febrifugine 6 is a new lead compound as a type of antimalarial drug (Scheme 1). Consequently, increasing efforts have been devoted to the development of useful preparation methods for the generation of quinazolines, which mainly involve: (1) oxidative coupling of anilines bearing an ortho -functional group with different carbon and nitrogen sources, 2-halobenzenes or 2-halobenzyl amination-involved cyclization, 7 2-nitrobenzonitrile as a precursor to 2,3-dihydroquinazolin-4(1 H )-ones in a combined reduction/hydration/cyclocondensation sequence, 8 cyclization of o -acylaminobenzamides, condensation of aryl, alkyl and heteroaryl aldehydes through nucleophilic addition to imines or iminium ions and then a cyclization reaction with anthranilamide, amidation of 2-aminobenzonitrile, followed by oxidative ring closure and Ir, Ru, Pt, Pd-catalyzed heterocyclization of nitroarenes. 9 However, most of the reported methods suffer from harsh reaction conditions, tedious procedures, stoichiometric and large excess amounts of toxic oxidants, long reaction times, and frequently, low yields.…”