Microwave-assisted synthesis of novel Mannich base and conazole derivatives containing biological avtive pharmacological groups
Background: The aim of this study is to synthesize new Mannich bases and conazol derivatives with biological activity by the microwave-assisted method. Introduction: 1,2,4-Triazole-3-one (3) acquired from tryptamine was transformed to the corresponding carbox(thio)amides (6a-c) via several steps. Compounds, 6a-c, were refluxed with sodium hydroxide to yield 1,2,4-triazole derivatives (7a-c). Compounds 3 and 7a-c on treatment with different heterocyclic secondary amines in an ambiance with formaldehyde afforded the Mannich bases 8-15 having diverse pharmacophore units with biologically active sites. The reaction of compound 3 and 2-bromo-1-(4-chlorophenyl) ethanone in the presence of sodium ethoxide gave the corresponding product yielded the corresponding 2-substituted-1,2,4-triazole-3-one, 16, which was reduced to 1,2,4-triazoles (17). Synthesis of compounds 18, 19, and 20 were carried out starting from compounds 17 with 4-chlorobenzyl chloride (for 18), 2,4- dichlorobenzyl chloride (for 19), and 2,6-dichlorobenzyl chloride (for 20). Method: The conventional technique was utilized for the synthesis of compounds, 3-7, and microwave-assisted technique for the compounds, 8-20. That is, green chemistry techniques were applied during these reactions. The structures molecules were elucidated on the foundation of 1H NMR, 13C NMR, FT-IR, EI-MS methods, and elemental analysis. Novel synthesized molecules were investigated for their antimicrobial activity using MIC (minimum inhibitory concentration) method. Results and Discussion: Aminoalkylation of triazole derivatives 3 and 7a–c with fluoroquinolones such as ciprofloxacin and norfloxacin provided an enhancement to the bioactivity of Mannich bases 8-11 against the tested microorganisms. The MIC values ranged between <0.24 and 3.9 μg/mL”. Moreover, molecules 10 and 11 have more effective on M. smegmatis than the other compounds by the MIC values of <1 μg/mL. They have shown very good antituberculosis activity. Conclusion: Most of the synthesized structures were observed to have excellent antimicrobial activity against most microorganisms taken into account. These molecules have activity better than the standard drug ampicillin and streptomycin.