Confined volume systems, such as microdroplets, Leidenfrost droplets, or thin films, can accelerate chemical reactions. Acceleration occurs due to the evaporation of solvent, the increase in reactant concentration, and the higher surface-to-volume ratios amongst other phenomena. Performing reactions in confined volume systems derived from mass spectrometry ionization sources or Leidenfrost droplets allows for reaction conditions to be changed quickly for rapid screening in a time efficient and cost-saving manner. Compared to solution phase reactions, confined volume systems also reduce waste by screening reaction conditions in smaller volumes prior to scaling. Herein, the condensation of glyoxal with benzylamine (BA) to form hexabenzylhexaazaisowurtzitane (HBIW), an intermediate to the highly desired energetic compound 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20), was explored. Five confined volume systems were compared to evaluate which technique was ideal for forming this complex cage structure. Substituted amines were also explored as BA replacements to screen alternative cage structure intermediates and evaluate how these accelerated techniques could apply to novel reactions, discover alternative reagents to form the cage compound, and improve synthetic routes for the preparation of CL-20. Ultimately, reaction acceleration is ideal for predicting the success of novel reactions prior to scaling up and determining if the expected products form, all while saving time and reducing costs. Acceleration factors and conversion ratios for each reaction were assessed by comparing the amount of product formed to the traditional bulk solution phase synthesis.
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