In the preliminary stage of chemical process design, the choice of chemical reaction route is the key design decision, and the concepts of atom utilization and environmental quotient have become extremely useful tools. However, the waste quality such as chemical toxicity and other engineering factors have not been taken into account. Therefore, a synthetic route selection index, I-Route is proposed to determine the suitability of a chemical route in this paper. I-Route considers the effects of "extended atom economy", material renewability, chemical characteristics and some engineering factors. The extended atom economy concept regards not only the value of the desired product but also the value of byproducts. The methodology by using I-Routes to compare different routes is illustrated in case study of cyclohexanone oxime and acrylonitrile manufacture.