Functionalization of 2-Methyl-3-o-tolyl-4(3H)-quinazolinone and Related Compounds through Carbanion Reactions at the 2-Methyl Group

Article abstract of DOI:10.1021/jo01299a027

2-Methyl-3-o-tolyl-4(3H)-quinazolinone (methaqualone, 3a), 2,3-dimethyl-4(3H)-quinazolinone (3b), and 2-methyl-3-phenyl-4(3H)-quinazolinone (3c) were converted to the 2-lithiomethyl derivatives 4a, 4b, and 4c, respectively, by means of lithium diisopropylamide in THF-hexane at 0 deg C.Reactions of 4a-c with a series of electrophilic reagents led to elaboration at the original 2-methyl group.Thus, 4a was alkylated with methyl iodide, allyl bromide, and ethyl bromide, sulfenylated with diphenyl disulfide, and condensed with benzaldehyde and cyclohexanone.Although 4a failed to react with benzophenone and showed a preference for enolization with acetone and butanone, the less hindered salt 4b added readily to the carbonyl group of benzophenone and acetone.Lithio salt 4c underwent self-condensation on treatment with cyclohexanone.Photostimulated phenylation of 2-potassiomethyl derivative of 3a was effected with iodobenzene.Lateral acylation of 3a was accomplished with esters of aliphatic and aromatic acids in the presence of excess sodium hydride.