On Demand Flow Platform for the Generation of Anhydrous Dinitrogen Trioxide and Its Further Use in N-Nitrosative Reactions

Abstract

Dinitrogen trioxide (N2O3) is a powerful and efficient nitrosating agent that comes with an unprecedented atom economy. However, the synthetic application of N2O3 is still underdeveloped mostly due to its inherent instability and the lack of reliable protocols for its preparation. This paper presents an open-source setup and procedure for the on-demand generation of anhydrous N2O3 solution (up to 1 M), which can be further used for reactions under batch and flow conditions. The accuracy and stability of N2O3 concentration are guaranteed with the absence of head-space in the setup and with the synchronization of the gas flows. The reliability of this protocol is demonstrated by >30 worked examples in the nitrosative synthesis of heterocycles—a library of structurally diverse benzotriazoles and sydnones. Kinetic and mechanistic aspects of the N-nitrosative steps are also explored.