Phthalides and their precursors have demonstrated a large variety of biological activities. Eighteen phthalides were synthesized and tested on the stored grain pest Rhyzopertha dominica. In the screening bioassay, compounds rac‐(2R,2aS,4R,4aS,6aR,6bS,7R)‐7‐bromohexahydro‐2,4‐methano‐1,6‐dioxacyclopenta[cd]pentalen‐5(2H)‐one (15) and rac‐(3R,3aR,4R,7S,7aS)‐3‐(propan‐2‐yloxy)hexahydro‐4,7‐methano‐2‐benzofuran‐1(3H)‐one (17) showed mortality similar to the commercial insecticide, Bifenthrin® (≥90 %). The time (LT50) and dose (LD50) necessary to kill 50 % of the R. dominica population were determined for the most efficacious phthalides 15 and 17. Compound 15 presented the lowest LD50 (1.97 μg g−1), being four times more toxic than Bifenthrin® (LD50=9.11 μg g−1). Both compounds presented an LT50 value equal to 24 h. When applied at a sublethal dose, both phthalides (especially compound 15), reduced the emergence of the first progeny of R. dominica. These findings highlight the potential of phthalides 15 and 17 as precursors for the development of insecticides for R. dominica control.