A. Khodair, Μ.M.A. Abbasi,, E. Ibrahim
1999
Citations
0
Influential Citations
4
Citations
Journal
Heterocyclic Communications
Abstract
4-Chloro-2-methyl-3-nitroquinolines 1-5 were used as precursors for the synthesis of heterocyclo[c]quinolines, where the nitro group plays different roles in the cyclization processes. Reduction of the 4-amino-3-nitro derivatives 6-10 to the 3,4-diaminoquinolines 11-14, and subsequent condensation with carbonyl compounds gave the corresponding imidazo[4,5-c]quinolines 15-24. Condensation of 1-5 with benzylamine or amino acids and subsequent cyclization gave the respective 3-hydroxy-2-phenylimidazo[4,5-c]quinolines 3034, and 35-43; 35 was cyclized to the imidazo[4,5-c]quinoline 44. Heating the 4-azido-3-nitroquinaldine 45 in benzene gave 1,2,5oxadiazolo[3,4-c]quinoline 46. Reaction of 2-5 with, salicylaldehyde and salicylic acid gave 47-50 and 51-54, respectively. Cyclization of either 47 or 51 and 48 or 52 gave the corresponding benzopyrano[3,2-c]quinolines 55 and 56. Introduction: Quinoline derivatives display a wide variety of biological properties. Thus, the 3and 4-amino derivatives, such as chloroquine and amodiaquine play a key role in the treatment of malaria [1-5] and the 3-amino acid derivatives are useful as antibacterial agents [6-9]. The 3-methyl sulphonyl derivatives are used in the treatment of heart failure and as antihypertensives [10-15], Indoloquino lines show a remarkable potent activity as antitumor agents [16,17]. Thiazoloquinolines are useful as fungicides [18] and pyrazoquinolines act as antibacterials, potent immunostimulants and interlukine inhibitors [19-22]. Imidazoquinolines act on benzodiazepine receptors, inhibitors of acid secretion and bone resumption, bronchodialators , inhibitor of blood platelets and antibacterials [23-26]. The main objective in the present work is the synthesis of fused heterocycles on site c of the quinoline ring, which can be of potential chemotherapeutic value. The versatility of the 4-chloro-2-methyl-3-nitro-6 or 7-substitutedquinolines 1-5 as precursors for generating the bifunctionality required for building heterocyclic rings on side c of the quinoline ring has been explored, whereby three various approaches for the utilization of the nitro group has been used. Results and Discussions The high reactivity of the 4-position in 4-chloro-2-methyl-3-nitroquinolines l -5[27] towards nucleophilic reagents can be due to the presence of the adjacent 3-nitro group. Thus, using, ammonia as a nucleophile in the displacement of the chlorine atom in 1-5 led to the formation of the 4-amino-2-methyl-3-nitro-6 or7-substitutedquinoline derivatives 6-10. The 'H nmr spectrum of 6 showed a D 2 0 exchangeable singlet for the amino group at 3.5 ppm. Reduction of the nitro group with stannous chloride gave the corresponding 3,4diamino derivatives 11-14 whose infrared spectra indicated the absence of the nitro group. The imidazoline ring could be generated from 11-14 by reaction with acetaldehyde to give 2,3-dihydro-2.4-dimethyl-7or 8-substitutedimidazo[4,5-c]quinolines 15-18. Condensation of 11 and 12 with acetic acid gave 7or 8-chloro-2,4-dimethylimidazo[5,4-c]quinolines 19 and 20, respectively. Reaction of 11-14 with lactic acid gave the respective 2-(l-hydroxyethyl)-4-methyl-7or 8-substitutedimidazo[5,4-c]quinolines 21-24. Condensation of 4-chloro-3-nitro-6or 7-substituted quinolines 1-5 with benzylamine gave the corresponding 4-benzylamino derivatives 25-29, which can be -yclized with sodium hydroxide to give 3-hydroxy-4-methyl-2-phenyl-7or 8-substitutedimidazo[5,4-c]quinolines