Directed Lithiation of Tertiary β-Amino Benzamides

Article abstract of DOI:10.1021/jo00369a002

The directed ortho-lithiation-alkylation of several tertiary β-amino benzamides was studied.The ortho-substituted β-amino benzamides were hydrolyzed directly with 6 N hydrochloric acid, or by a three-step, one-pot reaction involving methylation, elimination, and treatment with aqueous acid. o-Toluic acid, 2-n-butylbenzoic acid, 2-methoxy-6-methylbenzoic aicd, and 4-methoxy-2-methylbenzoic acid were prepared by using this ortho-metalation-hydrolysis methodology.Ortho-lithiation and reaction with benzaldehyde or dimethylformamide followed by hydrolysis with aqueous acid gave lactones in good yield.Methanolysis of N-(4-methoxy-2-methyl benzoyl)-N'-methylpiperizine with sulfuric acid/methanol gave methyl 4-methoxy-2-methylbenzoate in 71percent yield.The conversion of tertiary benzamides into ketones and aldehydes was examined.Treatment of certain tertiary benzamides with alkyllithium reagents gave ketones, while reaction with a modified aluminum hydride reagent gave aldehydes