The novel N-1 and C5 alkyl substituted derivatives of pyrimidine were synthesized by using tetrabutyl ammonium bromide (TBAB) as phase transfer catalyst at 20-25 °C with excellent productivity (85-95%). The new compounds were evaluated for their antibacterial activities by screening them against Gram-positive and Gram-negative bacterial strain: Staphylococcus aureus ATCC 6538P, Salmonella abony NCTC 6017: Escherichia coli ATCC 8739, Staphylococcus epidermidis ATCC 12228. Among all compounds evaluated the molecule 2c and (2g-j) exhibit the most pronounced antibacterial activity against E. coli, S. aureus and S. abony with MICs value 25 μg/mL.