A new class of α-aminophosphonates 2–16 has been synthesized by the reaction of equimolar quantities of Schiff's bases with diethyl/dimethyl/diphenyl phosphite in dry toluene under reflux conditions using tetramethylguanidine (TMG) as a catalyst via Pudovik reaction in high yields (78–89%). The structures of the title compounds have been established by elemental; infrared (IR); 1H-, 13C-, and 31P-NMR; and mass spectral data analyses. They were found to possess significant antimicrobial and antioxidant activity. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file. GRAPHICAL ABSTRACT