Synthese et reactivite de derivies de laquinoleique

Abstract

A number of polycyclic compounds containing a quinoline entity as a basic structural core were prepared using appropriate synthetic routes. In this work, a single base material was used: the 2-chloro-3-formyl-6-methylquinoline. Three series of compound derived from 2-phenylquinoline bearing at the position 3 respectively an amide function, ester and amine, linked to various groups such as a straight or branched chain alkyl having varying lengths, a five or six membered saturated cycle, and other aromatics, have been synthesized. The incorporation of an amine group in position 5 of the quinoline nucleus, and the functionalization of the aromatic methyl in position 6, has also been explored. The bromination reaction of the aromatic methyl with NBS provides selectively the mono or dibrominated derivative. The addition of morpholine to the monobrominated compound affords the corresponding amine, while the oxidation of ethyl 6-(dibromethyl)-2-chloroquinoléin-3-carboxylate by AgNO3 generates the aldehyde function. Several approaches using various reactions such as substitution reaction, addition- elimination (aldolization), cycloaddition, oxidation, reduction and other related synthesis methods have been developed for the preparation of 3-heteroaryl-2-phénylquinoléines. Some 2-phenylquinoline derivatives bearing at position 3, a pyrazole, pyrrole, oxazole, oxazolone, coumarin or quinoline, were prepared in good yields. The antimicrobial activity evaluation of prepared compounds, belonging to each of two themes, was carried out on five approved bacterial strains (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae and Salmonella thipymurium) using two different methods: the disk-diffusion, and the determination of minimum inhibitory concentration (MIC). The analysis of the results shows that most of the tested compounds are active against selected strains and some of them possess a remarkable bactericidal power (MIC ≤ 50 g / mL). The synthesis of condensed poly-heterocycles was undertaken and resulted in the preparation of few compounds derived from aza-coumarin analogs (benzo[6,7]-8-azacoumarins), and naphthydrin (benzo[6,7]-1,8-naphthydrins). The reactivity of 12-methyl-benzo[6,7]-8-azacoumarin and benzo[6,7]-1,12-dimethyl-1,2-dihydro-1,8-naphthydrin-3-carbonitrile through the 1,3-dipolar cycloaddition reaction of non-stabilized azomethine ylide, which is generated in situ by thermal decarboxylation of N-methyl-5-oxazolidinone, has also been explored. No reaction took place for the first one, but the second dipolarophile reacts correctly giving the condensed tetracyclic adduct, as expected. Yields are good, and structures of all prepared compounds were elucidated by usual spectroscopic methods (IR, NMR1H and C-13, and single-crystal-X-Ray diffraction).