Synthesis And Antibacterial Activity Of 1,4-disubstituted Phenyl-5-(halo-ο-hydroxyphenyl) Imino-1,2,3-triazoles

Many compounds containing triazole ring showed antibacterial, anti-HIV, anti-tumor andantisensitive activities in recent studies. Meanwhile, they also had specificity to the targets ofpathogen and strong affinity like lanosterol 14α-demethylase and HIV-RT. As a result, triazolederivatives in the design of novel biological and medical became more and more outstanding.Furthermore, o-hydroxyphenyl and halo-o-hydroxyphenyl group had strong affinity andspecificity to the targets of pathogen like FabI gene and NAD⁺coenzyme, which was the keystructures of o-hydroxydiphenyl ethers in antibacterial. As a results, the molecular segmentslike o-hydroxyphenyl and halo-o-hydroxyphenyl had broad application prospects in field ofnovel antibacterial medicine design. In addition, many study showed that many schiff basederivatives had good antibacterial, antitumor and anticancer activities. Therefore, 32 novel1,4-disubstitutedphenyl-5-（halo-o-hydroxyphenyl）imino-1,2,3-triazoles have been synthesizedbased on rational combination of 1,2,3-triazoles and halo-o-hydroxy phenyl according to thesuperposition principle of reinforcement of biological activities. All synthesized novelcompounds were screened for their in vitro antibacterial activities.In this paper, p-substituted aminobenzene was used as material, through diazotizationand azidation to obtain p-substituted phenylazide, then, 1,4-disubstitutedphenyl-5-amino-1,2,3-triazoles intermediates were synthesized from substituted phenylazide and p-methyl benzylcyanide in strong alkaline condition through a ring-closing reaction.Then the intermediateswere reacted with halo salicylaldehyde to obtain the target compounds. The studies haveshowed that the synthesis of intermediates was affected by the category of base （catalyst） andelectronic effect of substituted groups in aromatic ring. Strong base is good for p-methylbenzyl cyanide to eliminateαH and can enhance the stability of carbanion, increased theactivity of nucleophilic and was beneficial to nucleophilic reaction; Electron-donating groupsin benzyl cyanide aromatic ring of cyanide was beneficial to the activity of reaction, theelectronic effect of substituted groups in aromatic ring of phenylazide was contrary. Thesynthesis of target compounds was obviously influenced by the electronic effect of substitutedgroups in salicylaldehyde. The halogen groups in aromatic ring, especially the chlorine, couldincrease the activity and yield effectively.The antibacterial activities showed that all target compounds possessed efficientantibacterial activities against M.a., E.c. and S.a. at the concentration of 0.1 mg.mL-1, theywere better than the intermediates, even at the concentrations diluted to 0.01 mg.mL-1, most ofthe compounds still exhibited the antibacterial activities against E.s. and M.a., but almost haveno antibacterial activities against S.a..The study of structure-activity relationship showed that the o-hydroxyphenyl, especiallythe halo-o-hydroxyphenyl, could enhance the antibacterial activity of triazoles effectively, this conclucion coincidence in principle of reinforcement of biological activities. The substitutedgroup such as -Cl or -Br in the 1-phenyl enhanced the antibacterial activity effectively, but thegroup like–CH₃and–OCH₃would decrease it. The impact of the electronic effect ofsubstituted group in the 4-phenyl is not obvious.