Quinoline synthesis by improved Skraup-Doebner-Von Miller reactions utilizing acrolein diethyl acetal

A robust synthetic method has been developed as an improvement to the venerable Skraup-Doebner-Von Miller reaction providing access to various quinoline products. The straightforward procedure utilizes acrolein diethyl acetal as a three-carbon annulation partner with aniline substrates in a monophasic, organic solvent-free reaction medium. Differentially substituted aniline precursors were found to be compatible with the reaction conditions and the corresponding quinoline products are isolated in moderate to good yields. (C) 2015 Elsevier Ltd. All rights reserved.