From code to molecule: a versatile, modular, lab-scale automation strategy and platform for organic synthesis

Steiner, Sebastian (2018) From code to molecule: a versatile, modular, lab-scale automation strategy and platform for organic synthesis. PhD thesis, University of Glasgow.

Abstract

The work presented in this thesis focused on the automation of multistep organic syntheses on a laboratory scale in batch. Automation has received much attention in the chemical sciences and many automated synthesis solutions are commercially available or in development, yet all those solutions are focused on narrow aspects of the wider problem of automating chemical synthesis. In particular, a gap in the currently employed technologies was identified where synthesis in batch on a gram scale was concerned. Furthermore, many available solutions are monolithic and cannot easily be adapted for new applications, partially due to shortcomings of the hardware design, and partially due to the bespoke software controlling them.

To address this need for a new approach to automated synthesis, a novel strategy comprising hardware modules dedicated to individual unit operations (as opposed to other solutions built around specific chemical transformations and a modular flexible control software was developed. To enable the hardware development, liquid handling hardware was built and optimised, and four major modules for the unit operations of mixing under heating or cooling, liquid/liquid separation, filtration, and evaporation as well as several auxiliary modules were developed and tested.

The control software orchestrating the operation of the synthesis platform was modelled after a compiler in modern computer science, separating the synthetic operations from the physical hardware of the platform. This way, synthetic procedures can be transferred between different platforms, and new hardware modules can be added to the system at will. To enable the average synthetic chemist to use the system, a rudimentary scripting language for chemical operations was developed.

To prove the capabilities of the platform, three Active Pharmaceutical Ingredients (APIs) were synthesised in a fully automated fashion in yields and purities comparable to those obtained by hand. The automated reactions included a Grignard reaction and a chlorosulfonation, to name but a few. Additionally, the synthesis of one of the APIs was repeated on two physically different platforms simply by executing the same code on both systems.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Chemistry, synthesis, automation.
• Subjects: Q Science > QD Chemistry
• Colleges/Schools: College of Science and Engineering > School of Chemistry
• Supervisor's Name: Cronin, Professor Leroy
• Date of Award: 2018
• Depositing User: Sebastian Steiner
• Unique ID: glathesis:2018-30904
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 23 Oct 2018 11:01
• Last Modified: 17 Oct 2024 07:40
• Thesis DOI: 10.5525/gla.thesis.30904
• URI: https://theses.gla.ac.uk/id/eprint/30904