Synthesis And Antimicrobial Activities Of Carboxylate Ester And Methyl Benzimidazolone Derivatives

Benzimidazolones was widely used in many territories, their fungicidal activity is few oreven no papers available. Previous research has shown that acyl derivatives frombenzimidazolone have good antifungal activity against Botrytis cinerea. Base onbemzimidazolone derivatives were synthesized and some of their biological activities weretasted for further understanding structrue-activity relationship. The results were just asfollows.1. Derivatives of ethyl1-isopropyl-benzimidazolone-5(or6)-carboxylate (A01~A19，B01~B19) was prepared by the esterification, condensation, acylation of3,4-Diaminobenzoicacid. Derivatives of1-isopropyl-5-methyl-benzimidazolone (C01~C30) was prepared by thealkylation, amination, condensation, acylation of4-Methyl-2-nitroaniline. Their structureswere elucidated based on1H-NMR,13C-NMR and elemental analysis.2. Anti-bacteral activity in vitro against Bacillus cereus, Bacillus subtilis, Staphylococcusaureus, Escherichia coli and Pseudomonas aeruginosa were investigated by tablet diffusionmethod. Minimal inhibitory concentration (MIC) were tested by the broth microdilutionmethod. The results indicated that compounds A05, B05, C07and C02exhibited inhibitoryaction against all tested bacteria among the alkyl acyl derivatives. For α,β-unsaturated acylderivatives, both acroloyl and methacroloyl derivatives (A10, A11, B10, B11) exhibitedmoderate antibacterial activity, whereas the crotonoyl derivatives (A12and B12) had noinhibitory activity against the tested bacteria. The most potential of aromatic acyl derivativeswas A19and B19.3. Antifungal activity of compounds against Botrytis cinerea was evaluated by inhibitionspore germination. Commercial fungicides azoxystrobin and carbendazim were selected aspositive controls. Among acyl derivatives B04, C07, C02exhibited the strongest inhibitoryeffect against the spore germination of B. cinerea. B05only showed weak inhibition. A10andA11exhibited significant inhibitory effect against the spore germination of B. cinerea, andthere inhibition rate were95.27%and65.28%, respectively. Other α,β-unsaturated acylderivatives showed weak or even no inhibition. the most potential of aromatic acyl derivativeswas A15, C15, the p-chlorobenzoyl derivative, showed strong antifungal activity,4. The antifungal activity of compounds against Botrytis cinerea was evaluated by inhibition mycelial growth method. Commercial fungicides azoxystrobin and carbendazimwere selected as positive controls. A04and B04exhibited strong antifungal activity amongstalkyl acyl derivatives. Among α,β-unsaturated acyl derivatives, acryloyl and methacryloylderivatives(A10，A11，B10，B11) exhibited strong antifungal activity, whereas the crotonoylderivatives (A12and B12) only showed moderate or weak inhibitory activity against themycelial growth of B. cinerea. Among aromatic acyl derivatives, three pairs of m-methylbenzoyl (A15and B15), o-chlorobenzoyl (A17and B17) and p-chlorobenzoyl (A19and B19)derivatives exhibited strong inhibitory effect against the mycelial growth of B. cinerea.5. By means of investigating the Addition reactivity of α,β-unsaturated acyl derivativesof benzimidazolone in the reaction with glutathione. The broth microdilution method wasperformed to determined the minimal inhibitory concentration of the compounds D1-D6. Therelationship between antibacterial activity of tested compounds and addition reactivity wasinvestigated. The results indicated that the addition reactivity of α,β-unsaturated acylderivatives of benzimidazolone can not be used to quantitatively predict their antibacterialactivity.