Les dérivés poly-hétérocycliques

Abstract

A number of halo-1 -methyl-1 H-imidazole derivatives as basis materials such as 2-bromo-1 - methylimidazole (3), 2-bromo-5-nitro-1 -methylimidazole (6), 2,4,5-tribromoimidazole (7), and 4,5- dibromo(diiodo)-N-alkyl-1 -méthylimidazoles differently substituted at position 2 (8a-d), were prepared using various and appropriate methods as halogenation reaction (bromination and iodination), nitration, N-alkylation, and selective bromination. A quaternization reaction allowed us to prepare a variety of imidazolium salts carriers an electron-withdrawing group on the quaternary nitrogen, such as bromides of 4,5-dibromo (diiodo)-1 - methyl-1 H-imidazolium (16a-d), and a range of 2-bromo-1 -methyl-1 H-imidazolium bromide (17a-g), using as starting material 2-bromo-1 -methyl-1 H-imidazole. No evolution of the reaction was observed during the quaternization reaction of 2-bromo-5-nitro-1 -methyl-1 H-imidazole (6).The reactivity of these imidazolium salts has been then studied. The addition of CS2 in the presence of Et3Nt o the 4,5-dihalo-1 -methyl-1 H-imidazolium salts in acetonitrile ordioxane, shows no progress of the reaction, recovering the starting material as amajor product.The same procedure applied to 2-bromo-1 -methyl-1 H-imidazolium salts (CS2/Et3N, CH3CN, 25 °C) was successful and resulted in the synthesis of a series oforiginalbi-cyclic meso-ionic compounds: thethiazolo[3,2-a]imidazoles (18a-h),while the addition of KSCN in the presence of Et3N leads to a product corresponding to the substitution of the bromine at the 2-position by sulfur,the 2-(1 - méthyl-2-thio-1,2-dihydroimidazol-3-yl)-1 -aryléthanone (19a-b). Addition of arylamine provides the corresponding 2-arylamino-1 -methyl-1 H-imidazolium bromide (20a-e) along as econd minor product (<10%) identified to the N-phenacyl-2-imidazolone (21). Similarly, several series of highly functionalized poly-substituted imidazole derivatives (22a-f, 23a-c, 24a-c, 25a-cand26a-c) were prepared by N-alkylation reaction of 4,5-dihalo-1 -methyl-1 Himidazoles, and then subjected to evaluation of their antimicrobial activity. A variety of original poly-heterocyclic compounds as 1 -methyl-1 H-benzo[d]imidazole derivatives associated at 2-position with highlyunctionalized heterocycles such as 4H-pyrans (31-33), chromene (34), benzochromenes (35-36), 1,4-dihydropyridines (38-39), quinazolines (40-41), pyridines(42a-c), and pyrrolidines (44-45) were prepared from 1 -methyl-1 H-benzo[d]imidazole-2- carbaldehyde (29) using adequate and appropriate methods. Similarly, the preparation of structural analogues of Tacrine (a drug used in the treatment of Alzheimer's disease) has been explored, and three hybrid benzimidazole-tacrine compounds (46-48) have been prepared. Yields are good in most cases. All prepared compounds were identified by usual spectroscopic methods (IR, 1H NMR and13C), and for some of them additional analyzes were carried out (X-ray diffraction, and/or elemental analysis).