We describe a system, ChemSCAD, for the creation of digital reactors based on the chemical operations, physical parameters, and synthetic sequence to produce a given target compound, to show that the system can translate the gram-scale batch synthesis of the antiviral 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 anticancer agent Lomustine (batch yield 65% over two steps) in purities greater than or equal to 96%. The syntheses of compounds developed using the ChemSCAD system, including reactor designs and analytical data, can be stored in a database repository, with the information necessary to critically evaluate and improve upon reactionware syntheses being easily shared and versioned.

Chemistry digitization requires an unambiguous link between experiments and the code used to generate the experimental conditions and outcomes, yet this process is not standardized, limiting the portability of any chemical code. What is needed is a universal approach to aid this process using a well‐defined standard that is composed of syntheses that are employed in modular hardware. Herein we present a new approach to the digitization of organic synthesis that combines process chemistry principles with 3D printed reactionware. This approach outlines the process for transforming unit operations into digitized hardware and well‐defined instructions that ensure effective synthesis. To demonstrate this, we outline the process for digitizing 3 MIDA boronate building blocks, an ester hydrolysis, a Wittig olefination, a Suzuki–Miyaura coupling reaction, and synthesis of the drug sulfanilamide.

A combined experimental and density functional computational study was used to probe the mechanism for the reduction of indoles using simple borane BH 3 •DMS (DMS = dimethyl sulfide). Experimental and computational studies all steer to the formation of the reduced species 1-BH 2-indolines as the resting state for this reaction, as opposed to the historically presumed formation of the unreduced 1-BH 2-indoles, before the addition of a proton source to form the final product indolines. Furthermore, it was observed that molecular H 2 was generated and consumed in the reaction. Computations put forward hydroboration followed by protodeborylation as the very reasonable mechanistic route for the formation of experimentally observed major intermediate 1-BH 2 indolines. For the H 2 consumption in the reaction, computations suggest the frustrated Lewis pair-type heterolytic splitting of H 2 by a bis(3-indolinyl)borane intermediate.

<p>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.</p>

Chemistry digitization requires an unambiguous link between experiments and the code used to generate the experimental conditions and outcomes, yet this process is not standardized, limiting the portability of any chemical code. What is needed is a universal approach to aid this process using a well‐defined standard that is composed of syntheses that are employed in modular hardware. Herein we present a new approach to the digitization of organic synthesis that combines process chemistry principles with 3D printed reactionware. This approach outlines the process for transforming unit operations into digitized hardware and well‐defined instructions that ensure effective synthesis. To demonstrate this, we outline the process for digitizing 3 MIDA boronate building blocks, an ester hydrolysis, a Wittig olefination, a Suzuki–Miyaura coupling reaction, and synthesis of the drug sulfanilamide.