Study On The Synthesis Of Quinazoline Derivatives

Nitrogen-containing heterocyclic compounds widely exist in nature, many of them have a certain biological activity and drug activity. Because of their variety of chemical structures and displaying extensive biological activities, quinazoline derivatives attract much attention of researchers, and their synthetic method has been one of the hot topics, and innovative achievements are constantly presented. Although lots of synthetic methods of quinazoline derivatives have been reported, many of them exist shortcomings. In this paper, based on the original synthetic method, the synthetic route of 4-amino quinazoline compounds were modified and optimized, and two different paths, the synthesis of quinazoline derivatives and the reaction conditions,were studied and discussed. Using new synthetic method, 16 target compounds were prepared, of which 10 species have not been reported in literature., The new compounds were fully confirmed with NMR, IR and ESI-MS spectra.BThe first part is about one-pot method for synthesis of 4-aminoquinazoline derivatives using acetic acid as catalyst. The method incorporates condensation and Dimroth rearrangement to directly obtain quinazoline compounds, and so does not require separation of intermediates. Using the reaction of 2-aminobenzonitrile,DMF-DMA and aniline as a model, the reaction solvent, different kinds of acid catalysts and reaction temperature etc. are discussed. As a result, 13 target compounds were synthesized in 60%-75% yield, and the study demonstrated that this synthetic method was mild in reaction, benign to environment, and high quality of products.The second part is about a synthetic route of 4-aminoquinazolines using2-aminobenzoic acid, formamide, aniline as reactants. The method incorporates the condensation and chlorination to avoid the seperation of quinazolinone intermediates,and substituted quinazoline was prepared with one feeding with mild reaction condition and short reaction time. The study also improved the hydrolysis of nitrile compounds, 2-aminobenzoic acid can be prepared in 97% yield from2-aminobenzonitrile.The third part is about using composite solid acid catalyst to synthesize quinazoline derivatives Using one-pot reaction of 2-aminobenzonitrile, DMF-DMA and aniline as a model, the influence of different solid acid catalysts on the yiled of quinazolines, and catalyst activity and life, were discussed. The study shows that the solid catalyst is easy to separate and can be reused many times, hence conform to the green chemistry concept.