Design, Synthesis, Antibacterial And Antifungal Activities Of Novel Bis-triazoles And Their Cation Recognition

Triazole compounds have been paid great attention for pharmaceutists due to their virtues of higher efficacy,broader-spectrum and lower toxicity.Bis-triazole derivatives containing two triazole rings exhibit overwhelming advantages in supramolecular recognition and antimicrobial field,and have become the active research area in research and development of new drugs.This thesis focused on the research of bis-triazole compounds.Two new series of methylene- and propyl-bridged bis(1,2,4-triazole) compounds were designed and synthesized,and their recognization to metal cations were investigated,as well as their antimicrobial activities were evaluated.The main contents are as follws:By using different starting materials,methylene bis-triazole compounds were prepared through three synthetic routes.The cheap,easy,convenient and efficient synthetic methods were explored.The first synthetic route is to employ 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazol-1-yl) ethanone as starting material,the carbonylα-proton of the later was brominated by bromine to afford compound 32,and then N-alkylated with 1,2,4-triazole to give carbonyl bis-triazoles,further reduction of carbonyl group produced the corresponding compound 39a;the second is to start substituted benzene,the target compounds 39b-f were prepared by the Friedel-Crafts reaction, bromination,alkylation of triazole and reduction;the third is to use 1-p-tolyl-ethanone as the starting material,the bromination of 1-p-tolyl-ethanone,N-alkylation with 1H-1,2,4-triazole and then reduction of carbonyl group gave compound 39g.In addition,the bis-triazole ether compounds 40a-b and 42 were also synthesized.The recognition of methylene bis-triazole to metal cations were investigated.The results showed that compounds 38b and 38g exhibit strong compleation with Cu²⁺,Pb²⁺ and Ni²⁺ ions,but the coordination with Cd²⁺ ion was not obvious.In addition,the metal complexes 43 - 46 were prepared.Epichlorohydrin as starting material reacted with 1H-1,2,4-triazole in acetonitrile in presence of potassium carbonate to produce propyl bis-triazole alcohol 48.The intermediate 48 reacted with a series of alkyl or aralkyl halides to afford the desired propyl bis-triazoles 49a-h and 50a-d.The antimicrobial activities in vitro showed that methylenebis(1,2,4-triazole) compounds have better antifungal activity.Compounds 38a-g didn't show obvious antimicrobial activity. However,the compounds 39a-g with hydroxy group by the reduction of carbonyl compounds 38a-g enhanced antimicrobial activity.It is might be related to the better water-solubility for compounds 39a-g by introduction of hydroxy group.Halogenated substituents in benzene rings significantly effect on the antimicrobial activity,and the active order is p-C1＞p-F＞p-Br.Propyl bis-triazole 49g and 50b displayed better activity,and the activity of compound 49g against B. subtilis is similar to that Of the reference drug norfloxacin,and 49g gave moderate activity against A.fumigatus.It is notable that the compound 50b exhibited the best activity against all the tested strains,and the activity against S.aureus was comparable to the reference drug,close to the reference drug against B.subtilis and P.aeruginosa and it also showed moderate activity against B. proteus and B.coll.The new synthesized compounds were confirmed by UV-Vis,IR,¹H-NMR,¹³C-NMR and MS spectra.Metal complexes were characterized by X-ray power diffraction.In this thesis,38 compounds including 37 new ones were successfully synthesized,they were respectively 25 methylene bis-triazoles and their complexes and 12 propyl bis(1,2,4-triazole) compounds.