Copper-Catalyzed Domino Synthesis of Quinazolin-4(3H)-ones from (Hetero)arylmethyl Halides, Bromoacetate, and Cinnamyl Bromide

Abstract

Alkyl halides, including heteroarylmethyl and arylmethyl halides, bromoacetate, and cinnamyl bromide, are readily prepared via halogenation from basic raw materials, even using green processes. It is essential to replace their downstream products with them to prepare medicinally important heterocycles quinazolin-4(3H)-ones. Copper(I) bromide catalyzed domino reaction of alkyl halides and anthranilamides under air affords 2-substituted quinazolin-4(3H)-ones in good to excellent yields and with wide functional group tolerance. A mechanism for a copper(I) bromide involved organometal-catalyzed reaction via a four-step domino reaction is proposed.

Versatile Quinazolinone Synthesis: N‐Bromosaccharin‐Catalyzed Divergence in 2,3‐Dihydroquinazolin‐4(1H)‐one and Quinazolin‐4(3H)‐one Formation

“…Several synthetic methodologies have been developed for the construction of 2,3-dihydroquinazolin-4(1H)-ones, which mainly involves cyclocondensation of anthranilamide and aldehydes, intramolecular cyclization of a Schiff base and one-pot three-component reaction of isatoic anhydride, ammonium acetate or amine and an aldehydes. [3] For synthesizing quinazolin-4(3H)-ones, several protocols [4][5][6][7][8][9][10][11] have been developed. Quinazolin-4(3H)-ones were efficiently synthesized by the three-component cyclization-oxidation of isatoic anhydride, ammonium salts (or amine), and aromatic aldehydes in the presence of Ceric ammonium nitrate in ethanol, [12] CuOnanoparticles, [13] Bi(NO 3 ) 3 .5H 2 O, [14] thiamine hydrochloride (VB1), [15] L-prolinium nitrate (fully green amino-acid-based ionic liquid) inside the meso-channels of (α-Fe 2 O 3 )-MCM-41 [16] and Iodine.…”

Photogenerated chlorine radicals activate C(sp3)–H bonds of alkylbenzenes to access quinazolinones

“…In this context, various reactants have been developed to avoid the use of aldehydes. 10–15 Alkylbenzenes are promising raw materials for the synthesis of quinazolinones. 16 By activating the inert C–H bond on the benzylic carbon with applicable catalytic systems, 17 such as DTBP–TsOH/FeCl 3 , biopolymer-supported ferrite nanocatalysts, and heterogeneous Cu(OH) X /OMS-2, such commercial and inexpensive alkylbenzenes could undergo condensation with anthranilamides to form various quinazolinones with good yields (Scheme 1, (1) and (2)).…”

Discovery of Quinazolin-4(3H)-ones as NLRP3 Inflammasome Inhibitors: Computational Design, Metal-Free Synthesis, and in Vitro Biological Evaluation

“…The condensation of O -aminobenzamides with aldehydes in the presence of oxidants such as CuCl 2 , DDQ, MnO 2 , and KMnO 4 is one of the most elegant approach for its synthesis. In recent years, numerous protocols involving sp 3 carbon synthons such as benzyl halides, benzyl alcohols, and benzyl amines have been reported. Pd-catalyzed condensation with aryl halides via carbon insertion from CO or isocyanide is also reported.…”