Automatic Generation of 3D Printed Reactionware for Chemical Synthesis Digitization using ChemSCAD

Digital chemistry aims to define a hard link from the top abstraction layer in chemistry down to the synthesis, but this is difficult in traditional glassware since it is not possible to explicitly link the architecture with the unit operations. By 3D printing the synthesis modules in the precise order to affect the synthesis, it is possible to create digitally encoded reactors for chemical synthesis in ‘reactionware’. However, creation of these devices requires a specific skillset for CAD modelling which few synthetic chemists have. Herein, we describe an intuitive system, ChemSCAD, for the creation of digital reactor models based on the chemical operations, physical parameters and synthetic sequence to produce a given target compound. We demonstrate the ability of the ChemSCAD system to translate the gram-scale batch synthesis of the anti-viral compound Ribavirin (yield 43% over three steps), the narcolepsy drug Modafinil (yield 60% over three steps), and both batch and flow instances of the synthesis of the anti-cancer agent Lomustine (batch yield 65% over two steps) in purities ≥96%. The syntheses of compounds developed using the ChemSCAD system, including reactor designs and analytical data, can be stored in a single database repository where all the information necessary to critically evaluate, and improve upon, reactionware syntheses can be easily shared and versioned.