Design, Synthesis, Anion Recognition And Antimicrobial Activity Of Novel Imidazoles

Imidazole compounds possessed a wide range of potential uses as drugs with broad-spectrum biological activities such as antimicrobial,anticancer,histamine H₃ receptor antagonist and so on,as artificial receptors for molecule and ion recognition,and as artificial enzymes for biomimetic catalysis.Therefore,the research and development of imidazole compounds possessed great potential value and attracted much attention of many scientific workers.In this thesis,a series of sulfonamides imidazole compounds and sulfonyl piperazine imidazole compounds were designed and synthesized on the basis of the current status of imidazole compounds in the fields of antimicrobial activity and supramolecular recognition.The reaction conditions were explored,the antimicrobial activities were evaluated and the structure-activity relationships of these ne(?) compounds were also discussed.The intermediate 69 were synthesized through sulfonylation using aminoacenaphthene as starting material,and then alkylation with 1,2,4-triazole,imidazole and nitromidazole to afford sulphanilamide-azoles 71-73.The intermediate 69 were converted to sulfinic acid sodium,the resulting product was coupled with dibromide,and alkylated with imidazoles,2-methylimidazole and 5,6-dimethylbenzimidazole to give sulphanilamide alkyl imidazole 76 and sulphanilamide alkyl benzimidazole 77.Sulfonyl-piperazme-imidazole 84e was prepared by the reaction of sulfonyl chloride 69 with piperazine,chloroacetylation with chloroacetyl chloride,and then N-alkylation with imidzole.The intermediate 82a were synthesized by the reaction ofρ-toluene sulfonyl chloride with piperazine,and then chloroacetylated,and N-alkylated with imidzole or nitromidazole to give sulfonyl-piperazine-imidazole compounds 84a-d.Sulfonyl-piperazine -imidazole compound 86 were synthesized by the reaction of intermediate 82a with 1,2-bis(bromomethyl)benzene and then N-alkylation with imidzole.Piperazine-imidazole 89 was synthesized starting from 2,4-difluorobenzyl bromide and piperazine.2,4-difluorobenzyl bromide reacted with piperazine to produce halobenzyl piperazine and the resulting product was chloroacetylated and then reacted with imidazole to afford target amido piperazine-imidazole 89. The structures of these synthesized new compounds were confirmed by ¹H-NMR and MS spectra.The reaction conditions of chloride containing active at-hydrogen and its derivatives with imidazole were explored,and the optimum condition for the preparation of piperazine-imidazole compounds were obtained.The recognition abilities of compounds 70 and 72 as receptors to anions(Cl^?,I^?,Br^?, AcO^?,p-^? OOCPhCOO^? triazole^?,o-^? OOCPhCOO^?,H₂PO₄^?,^?HPO₄^?, PhCOO^?) were investigated.Compounds 70 and 72 showed good recognition to anions p-^? OOCPhCOO^?,o-^? OOCPhCOO^? and PhCOO^?.Moreover,benzimidazole compound 72 showed significant recognition to other tested anions,and compound 70 exhibited better selectivity for Br^?.The antimicrobial results in vitro showed that the antifungal activities for all the synthesized compounds against Aspergillus fumigatus were better than the clinical drug fluconazole,while their activity against Candida albicans were weaker than fluconazole.The antifungal and antibacterial activities for sulfonyl-piperazine-imidazole derivatives 84a-e were superior to sulphanilamide imidazole compounds 73a-d.In the series of sulfonyl-imidazole derivatives,sulfonyl azole with non-substituted benzene gave better results than methyl substituted the benzene sulfonyl azole, however,the acetamido substituted derivatives showed weak activity.Moreover,in the series of sulfonyl-piperazine-imidazole compounds,compound 84a containing amides displayed better than that of aromatic derivative 86.Among the piperazine-imidazole derivatives,those sulfonyl compounds 84a-e showed better activity than that non-sulfonyl compound 89. Sulphanilamide-piperazine-imidazole compound 84e was the best compound against S.aureus ATCC 29213,and two fold more efficient than norfloxacin.In this thesis,29 compounds were successfully synthesized,22 of them are new compounds, including 5 sulfanilamide azole compounds,4 sulfanilamide alkyl azole compounds,6 sulfonyl piperazine imidazole compounds,1 piperazine imidazole compound,3 bromides and 3 chlorides.