BACKGROUND In recent years, protoporphyrinogen oxidase (PPO, EC 1.3.3.4) inhibitors have been widely studied as important agricultural herbicides. Our research focused on the design and synthesis of novel PPO inhibitor herbicides, through linking of a diphenylether pyridine bioisostere structure to substituted coumarins, which aims to enhance environmental and crop safety while retaining high efficacy. RESULTS A total of 21 compounds were synthesized via acylation reactions and all compounds were characterized using infrared, 1 H NMR, 13 C NMR, and high-resolution mass spectra. The respective configurations of compounds IV-6 and IV-12 were also confirmed using single crystal X-ray diffraction. The bioassay results showed that the title compounds displayed notable herbicidal activity, particularly compound IV-6 which displayed better herbicidal activity in greenhouse and field experiments, crop selectivity and safety for cotton and soybean compared with the commercial herbicide oxyfluorfen. CONCLUSIONS The work revealed that compound IV-6 deserves further attention as a candidate structure for a novel and safe herbicide. © 2021 Society of Chemical Industry.