Abstract: In order to get a series of isocoumarin compounds with high herbicidal activity, 16 substituted oxadiazole 4a-4p were synthesized. All the target compounds were characterized by 1H NMR, 13C NMR and HRMS. Preliminary screening with Digitaria sanguinalis L. and Amaranthus retroflexus L. demonstrated that some of the target compounds exhibited herbicidal activity at the concentrations of 500 mg/L. 4j, 4-(5-(4-chlorophenyl)-1, 2, 4-oxadiazol-3-yl)-3-hexyl-6, 7-dimethoxy-1H-isochromen-1-one had the best effect to D. sanguinalis and A. retroflexus of which the mortality rates were 64% and 62%.