The importance of indirect hotspots when prioritizing research in green chemical synthesis†

A default assumption in green chemistry research and development is that every step of every process should be made as green as possible. That assumption is flawed. In some cases, a modification to an individual step that makes it more harmful is environmentally beneficial if the change decreases the harm or scale of another step. In this Perspective paper, we explain how the concept of an indirect hotspot can be used to understand the effects of any one step on the harm of another. A direct hotspot is a step that causes more harm than other steps. An indirect hotspot may cause very little harm on its own but has an outsized influence on the harm of the direct hotspot, and therefore the total harm of the process. These concepts can be used to prioritize green chemistry research, so that the environmental benefit of such research can be maximized.