Study On The Synthesis Of Quinoline Intermediates For Pharmacology

As a widely used organic intermediate, quinoline play an important role in the field of drug filtration, chemical analysis, dye industry, etc. Aminoquinoline(AQ) is one of the most prominence, its beneficial effects in the management of malaria caused huge attention in the pharmacologic research. The first antimalarial for clinic use was stem from AQ, since then, plenty of new structures with higher effect have been discovered. Up to now, not so much attention has been given to 6-aminoquinoline(6-AQ) derivatives as antimalarials in the drug filtration, this project describe further experiments in this series.In present paper, the progress of quinoline derivatives in synthesis and application are summarized first, then according to a lot of literature, designed the synthetic route for 8 derivatives of 6-AQ. They are 4-chloro-6-AQ, 5- chloro -6-AQ, 5-methoxyl-6-AQ, 7- chloro -6-AQ, 8- chloro -6-AQ, 8-bromo-6-AQ, 8-methyl-6-AQ and 8- methoxyl -6-AQ. All the products were obtained by reduction of its corresponding 6-nitroquinoline. To obtain the raw material of these 6-nitroquinolines, many synthesis methods were used: the pyridine ring substituted derivatives were synthesis by the electrophilic substitution, while the benzene ring substituted derivatives were synthesis by the Skraup-Doebner-Von Miller quinoline synthesis, electrophilic and nucleophilic substitution. There are some improvement to the Skraup-Doebner-Von Miller quinoline synthesis in this experiment: the arsenic acid, be used in classic synthesis route, was displaced by quinone with much lower toxicity; the usual violence of the reaction and the formation of tarry by-products both decreased if this reaction starts with acetanilide rather than the original aniline; the use of certain addictives also adjusted according to the constitution of each reaction. Through the investigations in a variety of reductant, it is found that when the halo- derivatives were subjected to strong reduction, such as NH2NH2·H2O/Pd-C or H2/Pd-C, dehalogenated product always be the majority. The structure of products have confirmed by 1HNMR, MS, and elementary analysis. Final results indicated that these improvements didn't give negative effects to reaction, the total yield for these product could reach 50%.All the reagents of the synthesis routes involved in this paper were basically no toxioity, this is identical to the need of modem society which advocates green chemistry and circumstance protection chemistry, it also offers both theoretical and experimental basis for studying new quinoline medicines.