Hazard Evaluation and Safety Considerations for Scale-Up of a Fuming Nitric Acid Mediated Nitration of Aryl Boronic Acids

Our laboratory has recently reported the highly efficient and chemoselective ipso nitration of aryl boronic acids using fuming nitric acid as the nitrating agent. Herein, we disclose and discuss the hazards associated with this reaction and the safety considerations that must be accounted for when increasing the scale of this process. Reaction Calorimetry was used to accurately determine reaction progress and revealed that careful, substrate-dependent selection of an appropriate reaction and reagent concentration and accurate titration of HNO3 are required to allow for safe and scalable use of this nitration process.