Several pyrazolo [1, 5-a] pyrimidines derivative were prepared by the condensation of substituted of α, β- unsaturated carbonyl compounds (chalcones) with substituted 5-amino pyrazole as an alternative polyethylene glycol (PEG-400) as green reaction medium. The reaction is clean with excellent yield, shorter reaction time. The entire synthesized products were characterized by spectral analysis. Furthermore, these newly synthesized compounds were screened for their antimicrobial activity against Escherichia coli (MTCC443), Bacillus subtilis (MTCC441), Staphylococcus aureus (MTCC96) and Salmonella typhi. (MTCC98). The antifungal activity was evaluated against Aspergillus niger, Aspergillus flavus (MTCC3008), Candida albicans (MTCC227) and Penicillium chrysogenum (MTCC160).Most of the compounds showed significant antimicrobial activity.