One-Pot Three-Component Synthesis of 4(3H)-Quinazolinones from Benzyl Halides, Isatoic Anhydride, and Primary Amines

Abstract

A novel, one-pot, and three-component synthesis of 4(3H)-quinazolinones is described. Benzyl halides are oxidized to aldehydes under mild Kornblum conditions then undergo a threecomponent reaction with isatoic anhydride and primary amines to produce 4(3H)-quinazolinones in excellent yields.

Crystal structure of 3-amino-2-ethylquinazolin-4(3H)-one

“…For related compounds, see: Ma et al (2013); Adib et al (2012); Xu et al (2012); Sasmal et al (2012); Kumar et al (2011); Rohini et al (2010); Davies et al (2010). For quinazolin-4(3H)-one ring-system modification through lithiation, see: Smith et al (2004Smith et al ( , 1996Smith et al ( , 1995.…”

“…Quinazolin-4(3H)-ones synthesis involves use of various synthetic procedures. The most common starting materials are 2-aminobenzonitrile (Ma et al, 2013), 2-bromobenzamides (Xu et al, 2012), isatoic anhydride (Adib et al, 2012), anthranilic acid (Kumar et al, 2011), methyl 2-aminobenzoate (Davies et al, 2010). Lithiation of 2-n-alkyl-and 2unsubstituted 3-acylaminoquinazolin-4(3H)-ones with a lithium reagent in tetrahydrofuran at a low temperature followed by reactions of various electrophiles with the lithium reagents produced in-situ gave the corresponding 2-substituted derivatives in good to excellent yields (Smith et al, 2004(Smith et al, , 1996(Smith et al, , 1995.…”

A novel and efficient synthesis of 2-substituted quinazolin-4(3H)-ones by the reaction of (het)arylmethanamines with isatoic anhydride

“…This broad range of applications has made the development of new and efficient quinazoline-4(3H)-ones syntheses valuable. Therefore, a number of synthetic routes have been reported for the preparation of quinazoline-4(3H)-one derivatives including: the FeCl3 catalysed reaction of isatoic anhydride with amidoximes, 16 the CuBr catalysed domino reaction of alkyl halides and anthranilamides, 17 the p-TSA-catalysed cyclization of 2-aminobenzamides and aldehydes followed by oxidative dehydrogenation with PhI(OAc)2, 18 the reaction of 2nitrobenzamides with aldehydes via in-situ reduction of the nitro group using Na2S2O4, 19 the C-C bond cleavage of 2,2disubstituted-1,2,3,4-tetrahydroquinazolinone by a CuBr/air catalytic system, 20 the three-component reaction of isatoic anhydride, primary amines and benzyl halides under Kornblum oxidation conditions, 21 the copper-catalysed domino Ullmanntype coupling and aerobic oxidative C-H amidation of 2halobenzamides and (aryl)methanamines, 22 the CuI catalysed…”

Cobalt(II) Chloride Catalyzed one Pot Synthesis of 2-substituted and 3-substituted-4(3H)- Quinazolinones

“…Many reagents have been reported in the literature, [15][16][17][18][19][20][21][22][23][24][25][26] for the synthesis of 4(3H)-quinazolinone derivatives. Among these methods 2-substituted-4(3H)quinazolinones have been synthesized from anthranilamide and aldehydes using NaHSO 3, 16a …”