This paper studied the catalysis of the Knoevenagel-phospha-Michael addition reaction for the synthesis of β-phosphonomalonates, known for their very interesting biological properties. The β-phosphonomalonate compounds as enzyme inhibitors and metabolic probes, as well as intermediates in organic synthesis, exhibit a wide variety of biological, anticancer, anti-inflammatory, antimalarial, and antimicrobial activities.Thecatalyst based on natural phosphate doped with zinc chloride was prepared and characterized by different analysis methods. Thus, various aldehydes with malononitrile and diethylphosphite were used to test the prepared catalyst. In order to investigate the best catalysts and operating conditions, natural phosphate, fluorapatite, and hydroxyapatite were tested as catalysts for this reaction. The findings, with a slight advantage for natural phosphate doped byzinc chloride, showed the existence of a synergy between zinc chloride and natural phosphate.