Engineering chemistry for the future of organic synthesis

Societal and commercial pressures are impacting more than ever on the methods and techniques by which we assemble today's functional molecules. A holistic appreciation of this complex eco-system necessitates the invention of new tools and stimulates innovative thinking. In particular, the labour intensive and unsustainable practices of the past are being replaced by a more machine-based approach. This engineering of chemistry goes beyond the design of simple, enabling mechanical contrivances to encompass a full range of artificial intelligence (AI) methods, machine learning algorithms, advanced robotics and reaction profiling techniques. Integration of these systems with data collection and evaluation are the new drivers for success. Access to wider process windows, improved mixing and mass and heat transfer methods are providing early kinetic data that aids discovery. Mechanochem, photo-redox and electrochemical devices are further adding to the repertoire of the synthetic chemist. Flow chemistry and continuous processing methods are similarly breaking new ground as delineated by many of authors in this Symposium in Print. Indeed, flow chemistry has proven to be very amenable to automation over several telescoped reaction steps leading to complex natural products and active pharmaceutical ingredients (API's) in particular. The modular nature and flexibility of these systems assists in designing reactor configurations that can accommodate in-line purification, which are increasingly being used in downstream product processing

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

Synthesis chemistry need not be limited to either only batch or only flow; rather, in the future we expect that it will consist of an amalgamation of the best and most appropriate methods. We have therefore devised a single reactor platform to conduct both batch and flow reactions, either singly or in concert, using open source technologies to automate, control and monitor individual processes. We illustrate this concept with the multistep synthesis of 5-methyl-4-propylthiophene-2-carboxylic acid to showcase the utility of this approach in a telescoped manner. Automated downstream processing techniques, consisting of continuous extraction and solvent switching steps, were also included, further freeing the chemist from routine laboratory tasks.Woolf Fisher Trust, Engineering and Physical Sciences Research Council (Grant IDs: EP/K009494/1, EP/M004120/1 and EP/K039520/1

Flow chemistry in Europe

This is an editorial for a Special Issu

Facilitating biomimetic syntheses of borrerine derived alkaloids by means of flow-chemical methods

Flow chemistry is widely used nowadays in synthetic chemistry and has increasingly been applied to complex natural product synthesis. However, to date flow chemistry has not found a place in the area of biomimetic synthesis. Here we show the syntheses of borrerine derived alkaloids, indicating that we can use biomimetic principles in flow to prepare complex architectures in a single step. This is the author's accepted manuscript. The final version is available from CSIRO Publishing in Australian Journal of Chemistry at http://www.publish.csiro.au/paper/CH14530.ht

Highly diastereoselective boron and titanium mediated aldol reactions of a mannitol derived 2,3-butanediacetal ethyl ketone

A mannitol derived 2,3-butanediacetal ethyl ketone displays high levels of diastereoselectivity in boron and titanium mediated aldol reactions with a range of aliphatic and aromatic aldehydes to afford syn aldol products in high yield. The stereochemical outcome of the reaction was determined using J-value analysis, NMR analysis of acetoxymandelate derivatives and X-ray crystallography

A Novel Internet-Based Reaction Monitoring, Control and Autonomous Self-Optimization Platform for Chemical Synthesis

We have developed a modular software system that enables researchers to monitor and control chemical reactions via the internet, using any device from any location in the world. It facilitates the automation of synthetic procedures and is able to autonomously self-optimize reaction parameters to find the best conditions meeting customizable, multi-component optimization functions. In this report, we demonstrate its utility as applied to reaction automation to maximize the output from a fixed volume of catalyst. We also showcase its ability to optimize a three dimension heterogeneous catalytic reaction and a five dimension Appel reaction against various target functions.We are grateful to the Woolf Fisher Trust (D.E.F), Pfizer Worldwide Research and Development (C.B.) and EPSRC (S.V.L., grant codes EP/K009494/1, EP/M004120/1 and EP/K039520/1) for financial assistance.This is the final version of the article. It was first available from American Chemical Society via http://dx.doi.org/10.1021/acs.oprd.5b0031

A tutored discourse on microcontrollers, single board computers and their applications to monitor and control chemical reactions

This Tutored Discourse constitutes a preliminary exposure on how synthesis chemists can engage positively with inexpensive, low-power microcontrollers to aid control, monitoring and optimisation of chemical reactions.H2020-FETOPEN-2016-2017 programme of the European Commission (grant agreement number: 737266-ONE FLOW

A multistep continuous flow synthesis machine for the preparation of pyrazoles via a metal-free amine-redox process

A versatile multistep continuous flow setup is reported for the four-step conversion of anilines into pyrazole products. The synthesis machine incorporates the use of amine-redox chemistry through diazotization and a metal-free vitamin C mediated reduction. The machine can be used for the synthesis of an array of analogues or the scale up of an individual target

Controlled generation and use of CO in flow

A tube-in-tube flow reactor allows the generation and immediate use of CO, without the need for CO cylinders.The authors gratefully acknowledge the EPSRC for financial support (grants EP/K009494/1 and EP/K039520/1) and the Danish Council for Strategic Research (grant 11-116196).This is the final version of the article. It first appeared from the Royal Society of Chemistry via http://dx.doi.org/10.1039/C6RE00020