Fouling of Flow Reactors in Organolithium Mediated Transformations: Experience on Scale-up and Proposed Solution

Continuous processing has been demonstrated to be a superior approach when applied to fast and energetic chemical transformations. Indeed, whereas classical batch or semi-batch methods require cryogenic conditions and slow addition rates of reactive chemistries, flow technologies enable a rapid mixing of synthetic partners in a highly controlled environment. As a result, low yielding and dangerous processes in batch can be performed at scale in a cost competitive and safer continuous modality. Despite high qualities and safety are common features, the perennial problem of solids build-up and pipes fouling always threatens the robustness and reliability of flow processes. Herein, a new methodology to prevent reactor clogging has been reported and discussed. The implementation of this new finding has been decisive to solve fouling issues encountered during the piloting of an organolithium based flow process