Digitizing Chemical Synthesis in 3D Printed Reactionware

Abstract

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.

Keywords: 3D Printing; Chemical Education; C−C Coupling; Reactionware; Unit Operations.

Figure 1

Traditional approach (left) and reactionware approach (right) to synthesis. In contrast to the traditional approach, a reactionware chemist will consider additional aspects on top of what is considered normally. All aspects in the traditional approach are inherently included in the reactionware approach when a chemical reaction is performed and recorded. The reactionware protocols are explicit, inherently including many process parameters, whereas the traditional approach is tacit in that a lot of considerations that were made by the chemist are lost in traditionally‐recorded protocols.

Figure 2

a) Process flow diagram displaying unit operations and their sequence (P: product), b) 3D‐printed reactionware as designed ChemSCAD, c) compound 3 product powder, d) reaction scheme for MIDA boronate ester synthesis (%Yield of compound prepared in reactionware is in bold with %Yield as prepared in glassware is in parentheses).

Figure 3

a) Process flow diagram displaying unit operations and their sequence for ester hydrolysis (P: product), b) 3D‐printed reactionware as designed using ChemSCAD, c) carboxylic acid product powder, d) reaction scheme for ester hydrolysis (%Yield of compound prepared in reactionware is in bold with %Yield as prepared in glassware is in parentheses).

Figure 4

a) Process flow diagram displaying unit operations for Wittig olefination (P: product, BzTPPCl: benzyl triphenylphosphonium chloride), b) 3D‐printed reactionware as designed using ChemSCAD, c) alkene product crystals, d) reaction scheme for Wittig olefination (%Yield of compound prepared in reactionware is in bold with %Yield as prepared in glassware is in parentheses).

Figure 5

a) process flow diagram displaying unit operations and their sequence for Suzuki–Miyaura coupling (P: product), b) 3D‐printed reactionware as designed using ChemSCAD, c) compound 6 product crystals as prepared using Method 1, d) reaction scheme for Suzuki coupling (%Yield of compound prepared in reactionware is in bold with %Yield as prepared in glassware is in parentheses).

Figure 6

a) process flow diagram detailing unit operations for the synthesis of sulfanilamide (P: product), b) 3D‐printed reactionware as designed using ChemSCAD, c) Sulfanilamide product powder, d) reaction scheme for multi‐step sulfanilamide synthesis (%Yield of compound prepared in reactionware is in bold with %Yield as prepared in glassware is in parentheses).

Figure 7

Comparison of yields obtained from literature procedures in glassware and translated procedures in reactionware. Entries sorted by the number of unit operations. The Δ %Yield is difference in %Yield between glassware and reactionware. * Yields not disclosed in student manuals. ** No literature data as this compound was prepared using a before‐unused substrate based on a general procedure. *** No literature data as this method was developed in‐house.