Engineering chemistry for the future of chemical synthesis

doi:10.1016/j.tet.2017.08.050

Tetrahedron

Volume 74, Issue 25, 21 June 2018, Pages 3087-3100

https://doi.org/10.1016/j.tet.2017.08.050 Get rights and content

Abstract

Synthesis is changing in response to our modern resource conscious world. The principles of green chemistry are evolving as the interfaces and boundaries in science are less obvious and providing a new stimuli for future discovery. The invention and application of new chemical reactivity continues to be a primary driver since this opens up so many strategic opportunities for synthesis. However, the manual intensive efforts behind such activity inevitably lead to the need for more machine based approaches. Indeed, the engineering of chemistry delineated in this Symposium in Print seeks to collate some of the recent progress and innovation in the area with contributions from its visionary practitioners.

Graphical abstract

Section snippets

Introduction and preamble

We live in a world where complex machinery impacts widely on all our activities. Even our motor cars and airplanes can now operate autonomously. The same however, is not true of a modern chemical synthesis laboratory where many of the tasks are still manual, often routine and repetitious in nature. Even the expensive equipment in this environment is often isolated and the data collected tends to be siloed and not fully utilized. Our batch-mode mentality promotes incremental development at the

The early days

Firstly we need to put our science into context. While modern developments in computers have allowed new avenues for chemical research to flourish, the idea of implementing control systems to aid in synthesis certainly is not new. For example, one of the earliest reports, dating back to 1965, details how an automated approach to solid-phase peptide synthesis enabled the preparation of two polypeptides – Bradykinin and Angiotensin II – with minimal researcher intervention.¹² In this case the

The rise of LabVIEW

In 1986, a US-based company named National Instruments released version 1.0 of their Laboratory Virtual Instrument Engineering Workbench software for the Macintosh operating system, followed six years later with versions compatible with Sun and Windows operating systems. Commonly referred to as LabVIEW,¹⁷ this tool was designed to facilitate the collection of data from and control of laboratory and industrial equipment.

LabVIEW's visual interface is a key feature that differentiates it from

Machine vision

Before describing the state of computer-powered automation tools in use today, we felt it would be worth briefly outlining the world of machine vision and its application in chemical synthesis. While we have extensively reviewed literature in this area previously,²⁸ here we want to provide an overview of the utility of these methods.

By giving the ‘sense’ of sight to our computer control systems, we can both monitor and control experimental procedures that normally rely on visual feedback. Some

The state-of-the-art, today

There has been a surge of interest in recent times to apply automation to aid with the development and synthesis of specific active pharmaceutical ingredient (API) targets, right from a discovery scale to process scale chemistry. This has been reported for both the control of telescoped steps³⁴ and the optimisation of reactions corresponding to individual steps.³⁵

The future of automated control

We believe the future of computer-powered automation is vast and has potential to impact every part of a modern scientist's work. As we have seen in many other areas, developments in one discipline or technological sector can be applied in others with great success. Chemistry is no different.

Conclusions

In this lead article for this Symposium in Print, we have briefly reviewed some of the science that is developing not to fully automate the full repertoire of synthetic chemistry - this is unlikely to happen in the foreseeable future - but to better engineer chemistry to facilitate discovery. In a rapidly evolving scientific world, constituent elements such as chemistry must become more responsive and adapt or face becoming redundant.

Synthesis is inherently an experimental subject requiring the

Acknowledgements

The authors gratefully acknowledge support from the Woolf Fisher Trust (DEF), ECH2020 Future and Emerging Technologies (SVL. Sponsor reference 206410) and the Engineering and Physical Sciences Research Council (SVL. Grant codes: EP/K009494/1, EP/M004120/1).

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PerspectivesEngineering chemistry for the future of chemical synthesis

Abstract

Graphical abstract

Section snippets

Introduction and preamble

The early days

The rise of LabVIEW

Machine vision

The state-of-the-art, today

The future of automated control

Conclusions

Acknowledgements

Tetrahedron Lett

Org Process Res Dev

Org Process Res Dev

European J Org Chem

Org Process Res Dev

Tetrahedron Lett

Org Biomol Chem

Networks

Org Process Res Dev

Enabling technologies for the future of chemical synthesis

ACS Cent Sci

Organic synthesis: march of the machines

Angew Chemie Int Ed

Machine-assisted organic synthesis

Angew Chem Int Ed

Feedback in flow for accelerated reaction development

Acc Chem Res

Assessment of recent process analytical technology (PAT) trends: a multiauthor review

Org Process Res Dev

On being green: can flow chemistry help?

Chem Rec

A systems approach towards an intelligent and self-controlling platform for integrated continuous reaction sequences

Angew Chem Int Ed Engl

A flow process for the multi-step synthesis of the alkaloid natural product oxomaritidine: a new paradigm for molecular assembly

Chem Commun

Automated synthesis of peptides

Science

Preparation of the neolignan natural product grossamide by a continuous-flow process

Synlett

Fully automated continuous flow synthesis of 4,5-disubstituted oxazoles

Org Lett

Fully automated flow-through synthesis of secondary sulfonamides in a binary reactor system

J Comb Chem

A flow-based synthesis of Imatinib: the API of Gleevec

Chem Commun

ReactIR flow cell: a new analytical tool for continuous flow chemical processing

Org Process Res Dev

A fully automated, multistep flow synthesis of 5-amino-4-cyano-1,2,3-triazoles

Org Biomol Chem

A breakthrough method for the accurate addition of reagents in multi-step segmented flow processing

Chem Sci

Self-optimizing continuous reactions in supercritical carbon dioxide

Angew Chem Int Ed

A simplex method for function minimization

Comput J

Automated multitrajectory method for reaction optimization in a microfluidic system using online IR analysis

Org Process Res Dev

A LabVIEW based template for user created experiment automation

Rev Sci Instrum

Camera-enabled techniques for organic synthesis

Beilstein J Org Chem

Hydrogenation in flow: homogeneous and heterogeneous catalysis using Teflon AF-2400 to effect gas–liquid contact at elevated pressure

Chem Sci

A prototype continuous-flow liquid-liquid extraction system using open-source technology

Org Biomol Chem

Continuous multiple liquid-liquid separation: diazotization of amino acids in flow

Org Lett

Continuous flow liquid–liquid separation using a computer-vision control system: the bromination of enaminones with N-Bromosuccinimide

Synlett

Engineering chemistry: integrating batch and flow reactions on a single, automated reactor platform

React Chem Eng

Self-optimisation of the final stage in the synthesis of EGFR kinase inhibitor AZD9291 using an automated flow reactor

React Chem Eng

Perspectives
Engineering chemistry for the future of chemical synthesis