Synthesis Of Quinolines And Quinazolines

Quinolines and quinazolines are two important chemical classes of nitrogen-containing heterocyclic compounds that possess a wide spectrum of biological activities such as antibacterial and antitumor. Besides, they are key synthons for the construction of various medicines. The researches of this thesis were focused on the green and efficient syntheses of quinolines and quinazolines. The details are summarized as following:1. A new Skraup-Doebner-Von Miller quinoline synthesis. The Skraup-Doebner-Von Miller quinoline synthesis, which was often carried out using protic acids, gave predominantly traditional quinolines via the condensation of unsaturated carbonyl compounds with anilines. In this thesis, quinolines with a reversed regiochemistry were obtained by introducing a trifluoromethyl group, a strong electron-withdrawing group, into unsaturated carbonyl compounds. This protocol possessed many advantages such as reversed regiochemistry, mild reaction conditions and simple manipulations.2. Two modified Friedl?nder quinoline synthesis. Friedl?nder synthesis was one of the simplest and most straightforward methods to produce quinolines, yet 2-aminobenzaldehyde, as a typical starting material for a Friedl?nder quinoline synthesis, can readily undergo self-condensation and thus limited the scope and generality of the Friedl?nder quinoline synthesis. Therefore, this thesis focused on the optimization of Friedl?nder synthesis method. On one hand, a modified Friedl?nder quinoline synthesis has been developed by an iron-catalyzed redox condensation of 2-nitrobenzyl alcohol, formic acid and an alcohol. The protocol agreed well with the principle of green chemistry since water and carbon dioxide were the only by-products. On the other hand, another modified Friedl?nder quinoline synthesis has been developed by KOtBu-promoted redox condensation of 2-nitrobenzyl alcohol with acetophenone in Me OH. 2-Nitrobenzyl alcohol was found to readily undergo redox in KOtBu/Me OH reaction system to produce a reactive 2-aminobenzaldehyde and the latter was condensed with acetophenone to convert in situ to quinoline. The modified Friedl?nder quinoline synthesis could be accomplished under mild reaction conditions and without the use of catalysts, and thus was attractive from an economic point of view.3. A new quinazoline and hydrazone synthesis. This section was based on the synthesis research of quinolines under base condition, which selected 2-nitrobenzyl alcohol and benzylamine for the syntheis of quinazolines. The 2-phenyl quinazoline was accomplished successfully in the presence of KOtBu and tBu OH in 70% yield. When Me OH was used as the solvent instead of tBu OH under otherwise the same conditions, a hydrazone was obtained exclusively. The method was the first time to generate quinazolines and hydrazones under the base condition.