Accelerated synthesis of energetic precursor cage compounds using confined volume systems

Abstract

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.

Low-cost, automated reaction screening for energetic precursor cage compounds by a benchtop liquid handling robot and desorption electrospray ionization mass spectrometry

“…12 Microdroplets formed by DESI 13 or other electrospray ionization techniques have been used extensively as microreactors for reaction acceleration. 14 As a result, there have been reports that product formation is achieved orders of magnitude faster in microdroplets than the same reaction performed in bulk. 15 These interfacial microdroplet reactions are proposed to have faster rate constants and reaction rates, due to the larger surface-to-volume ratios and air–liquid interfaces compared to conventional bulk synthesis.…”

Accelerated formation of trioximes through confined volume reactors and scale-up using thin film methods

“…Confined-volume systems have recently been applied to form energetic precursors and novel analogues for accelerated screening. 11 Confined volume systems, such as microdroplets, 12 Leidenfrost droplets, 13 and thin films, 14 have been used to accelerate organic reactions. The rate constants and reaction rates for these interfacial reactions, with larger surface-to-volume ratios and air–liquid interfaces are typically much faster compared to conventional bulk synthesis methods.…”

Aqueous microdroplets enable abiotic synthesis and chain extension of unique peptide isomers from free amino acids

“…Of particular interest is the observation that the air–water interface of monolayers and thin films ( 28 – 31 ), inverted micelle aerosols ( 12 ), Leidenfrost droplets ( 32 – 36 ), and charged or neutral microdroplets ( 37 – 46 ) all reveal vastly different chemical kinetics compared to bulk, with rate constants increased by up to six orders of magnitude ( 47 , 48 ). This interfacial acceleration phenomenon has been reported for prebiotically relevant reactions including condensation ( 12 , 21 , 29 , 49 – 53 ), redox ( 54 , 55 ), nucleophilic addition ( 41 , 43 ), and ultraviolet-initiated photopolymerization reactions ( 56 ).…”