The 1-aminophthalazine derivatives (7a-d) were prepared by the reaction of 1-chloro-4-(4`-methoxyphenyl) pthalazine compound 5 with 1, 2-phenylene diamine 6a or 1, 3-phenylene diamine 6b dissolved in DMF while ethylenediamine 6c or 1,4-diaminobutane 6d dissolved in ethanol. The resulting new α-aminophosphonate compounds (10a-f) were produced by combining derivative of 1-aminophthalazine derivatives 7, aldehyde 8 and triphenyl phosphite 9 then LiClO4 as a Lewis acid catalyst was added. The chemical structures of all the produced compounds were determined by IR, 1H-NMR, 13C-NMR, 31P-NMR, and mass spectroscopic methods. The antimicrobial activities of the synthesized compounds were in vitro screened against gram-positive bacteria, gram-negative bacteria and fungi pathogens. The majority of synthesized compounds have moderate to good antimicrobial efficacy.