Accelerated tert-butyloxycarbonyl deprotection of amines in microdroplets produced by a pneumatic spray

Protection and deprotection of organic compounds in multistep reactions using functional groups such as tert-butoxycarbonyl (Boc), is widely performed in synthetic organic chemistry. Reaction rate acceleration studies in spray-based ionization methods (electrosonic spray, paper spray, nanospray) have become increasingly common. Here, we demonstrate reaction rate acceleration of Boc deprotection using easy ambient sonic-spray ionization (EASI), a pneumatic technique which does not involve an applied voltage, in a teaching laboratory setting. The goal of this laboratory exercise was to explore acceleration in a previously unexplored spray-based reaction, while emphasizing in a pedagogic setting the importance of protecting groups for multistep synthesis. Rate acceleration factors of more than an order of magnitude were observed in the uncharged micron-sized droplets generated by EASI. The effect of reaction conditions on reaction acceleration was examined including changes in the type of acid, reagent concentration ratios and syringe pump flow rates. Student knowledge was assessed by pre-laboratory assignments, post-laboratory reports and oral interviews. (C) 2018 Elsevier B.V. All rights reserved.