Synthesis of Some Novel fused pyrazolo[4,5-e]pyrimidine derivatives bearing oxa/thiadiazole Nucleus as Potential Antimicrobial Agent

Abstract

A series of some novel fused 1-(substituted phenoxymethyl)-7-(4-tolyloxymethyl)-4-oxopyrazolo [4,5-e][1,3,4]oxadiazolo[2,3-b]pyrimidine (2) & 1-(2-chlorophenoxymethyl)-7-(4-tolyloxymethyl)-4-oxopyrazolo-[4,5-e][1,3,4]thiadiazolo[2,3-b]pyrimidine (3) derivatives have been synthesized from Michael adduct 1-(2-methylphenoxymethyl)-5-amino-4-carboethoxypyrazoles (1) respectively which in turn have been prepared via intermolecular Michael addition, followed by cyclisation reaction between tolyloxyacetohydrazine and ethyl-2-cyano-3-ethoxyacrylate in methanol and  glacial acetic acid as catalyst.  The Michael adduct (1) afforded fused system (2) & (3) via nucleophilic addition followed by cyclisation with 2-(4-tolyloxymethyl)-5-mercapto-1,3,4-oxadiazole and 3-(4-chlorolphenyl)-5-mercapto-1,3,4-thiadiazole, respectively. The structures of these compounds have been established on the basis of spectral data IR, ¹H NMR, ¹³C NMR and elemental analysis. All the synthesized compounds have been screened for antibacterial activity against Escherichia coli, Pseudomonas aeruginosa Streptococcus pneumonia and Bacillus subtilis and antifungal activity against fungi viz. Candida albicans, Aspergillus fumigatus, Aspergillus havue and Aspergillus niger. The results showed that these compounds are better antibacterial and antifungal agent as compared to the standard drug ciprofloxacin and fluconazole respectively.