Join Christopher Thomson, Researcher at Heriot-Watt University, as he shares his work expanding the tool kit of automated flow synthesis with the development of in-line flash chromatography purification.
In this webinar, you will learn:
An introduction to flow chemistry and in-line purification technologies.
An overview of prior continuous chromatography methods, their advantages and limitations.
How to interface flow reactors with puriFlash automated chromatography systems.
‘Tips & Tricks’ for performing continuous in-line flash chromatography.
Future prospects for developing in-line flash chromatography.
Chris completed his chemistry with biochemistry degree (MChem, 1st Class) at Heriot-Watt University, Edinburgh, in 2018 and was recipient of the ‘William H. Perkin Prize’ for excellence in organic chemistry. He was then awarded a PhD scholarship through the EPSRC funded centre for doctoral training in critical resource catalysis (CRITICAT), under the joint supervision of Dr Filipe Vilela and Dr Ai-Lan Lee.
Chris’ research focuses on the development and implementation of enabling technologies – especially flow chemistry – to enhance heterogeneous photocatalysis for organic synthesis.
He has published several papers on the development of flow systems featuring enabling technologies, such as: in-line NMR spectroscopy, in-line UV-Vis. spectroscopy, static mixing photocatalyst monoliths produced via functional material additive manufacturing, and most recently, reported the first example of continuous in-line flash chromatography – which will be the subject of this webinar.
In this application note, we describe a novel method to perform the continuous isolation of flow synthesis products from residual starting materials, catalysts or by-products to expedite chemical discovery. A promising new approach is highlighted here, featuring the Advion Interchim Scientific puriFlash® 5.250 preparative LC system.
The first results of our cooperation with the VilelaLAB and Continuum Flow Lab at Heriot-Watt University, Edinburgh, on this topic are outlined here and can be read in more detail in the following source: C.G.Thomson et al.: Expanding the Tool Kit of Automated Flow Synthesis: Development of In-line Flash Chromatography Purification, J. Org. Chem. 2021, 86, 20, 14079–14094.
Research methods that predict Fe bioavailability for humans can be extremely useful in evaluating food fortification strategies, developing Fe-biofortified enhanced staple food crops and assessing the Fe bioavailability of meal plans that include such crops. In this review, research from four recent poultry (Gallus gallus) feeding trials coupled with in vitro analyses of Fe-biofortified crops will be compared to the parallel human efficacy studies which used the same varieties and harvests of the Fe-biofortified crops. Similar to the human studies, these trials were aimed to assess the potential effects of regular consumption of these enhanced staple crops on maintenance or improvement of iron status. The results demonstrate a strong agreement between the in vitro/in vivo screening approach and the parallel human studies.
LC/MS analysis was complete using the Advion expression Compact Mass Spectrometer (CMS). Instrumentation and data acquisition were controlled by Advion Mass Express software
The synthesis of diazonium salts is historically an important transformation extensively utilized in dye manufacture. However the highly reactive nature of the diazonium functionality has additionally led to the development of many new reactions including several carbon-carbon bond forming processes. It is therefore highly desirable to determine optimum conditions for the formation of diazonium compounds utilizing the latest processing tools such as flow chemistry to take advantage of the increased safety and continuous manufacturing capabilities. Herein we report a series of flow-based procedures to prepare diazonium salts for subsequent in-situ consumption.
Flow reactor loading set-up.
Direct in-line mass spec analysis was performed using the Advion Interchim Scientific® expression® Compact Mass Spectrometer (CMS) with electrospray ionization (ESI).
The discovery of chemical reactions is an inherently unpredictable and time-consuming process. An attractive alternative is to predict reactivity, although relevant approaches, such as computer-aided reaction design, are still in their infancy. Reaction prediction based on high-level quantum chemical methods is complex, even for simple molecules. Although machine learning is powerful for data analysis, its applications in chemistry are still being developed6. Inspired by strategies based on chemists’ intuition, we propose that a reaction system controlled by a machine learning algorithm may be able to explore the space of chemical reactions quickly, especially if trained by an expert. Here we present an organic synthesis robot that can perform chemical reactions and analysis faster than they can be performed manually, as well as predict the reactivity of possible reagent combinations after conducting a small number of experiments, thus effectively navigating chemical reaction space. By using machine learning for decision making, enabled by binary encoding of the chemical inputs, the reactions can be assessed in real time using nuclear magnetic resonance and infrared spectroscopy.
Ana A. Folgueiras-Amador, Kai Philipps, Sébastien Guilbaud, Jarno Polacker, Prof. Dr. Thomas Wirth
Flow electrochemistry is an efficient methodology to generate radical intermediates. An electrochemical flow microreactor has been designed and manufactured to improve the efficiency of electrochemical flow reactions. With this device only little or no supporting electrolytes are needed, making processes less costly and enabling easier purification. This is demonstrated by the facile synthesis of amidyl radicals used in intramolecular hydroaminations to produce isoindolinones. The combination with inline mass spectrometry facilitates a much easier combination of chemical steps in a single flow process.
The in-line MS analysis was carried out using Advion Expression® CMS (Atmospheric Pressure Ionisation Techniques (APCI)) and an MRA® valve.
Q: WHAT IS THE FOCUS OF YOUR LAB’S RESEARCH? A: One of the focus points for Ley Group research is the development of continuous flow synthesis methods. We aim to include new enabling techniques into our work to facilitate the collection of data relevant to the reactions we conduct. We work across the early synthesis spectrum – from discovery to scale-up and process development.
Q: WHAT WAS YOUR PREVIOUS WORKFLOW AND EXPERIENCED CHALLENGES?
A: Standard detectors we use in our work can be problematic when trying to discern what is in a product mixture leaving a flow reactor. For example, UV detectors are useful only in very restricted flow-based situations and don’t give compositional information. IR is a step up from this, but suffers from issues when peaks in starting materials, products and by-products overlap. Some transformations may also lead to undetectable changes in an IR spectrum. While flow-based NMR can be good when it’s usable, its expense and lack of resolution at a bench-top level hinder its utility.
Q: WHY DID YOU INCORPORATE THE EXPRESSION® CMS INTO YOUR LABORATORY?
A: The expression® CMS struck the perfect balance between cost, ease-of-use and detection capabilities that we needed for our research. We’re able to get large amounts of relevant information about reaction mixtures, in real-time, without worrying in most cases about overlapping peaks or detection signals. This information is used by our control systems to make decisions about product stream composition, allowing us to automate procedures such as reaction telescoping, process start up and self-optimization. The expression® CMS software is fantastic also – everything is recorded, letting us go back over the raw data to gain even more insights into how product compositions change over time in our processes.
Q: TO WHOM WOULD YOU RECOMMEND THE EXPRESSION® CMS?
A: I would recommend the system to any group that works with continuous flow chemistry, especially those that need real-time analysis of stream compositions. The ease at which the unit can be integrated into any process makes it an extremely attractive unit to use. It’s also very easy to switch the expression® CMS into a standalone MS unit for independent sample analysis, making it versatile in any organic chemistry laboratory.
Q: HAVE YOU CONTRIBUTED TO ANY PUBLICATIONS USING THE EXPRESSION® CMS?
N. Holmes, G.R. Akien, R.J.D. Savage, C. Stanetty, I.R. Baxendale, A.J. Blacker, B.A. Taylor, R.L. Woodward, R.E. Meadows, and R.A. Bourne
An automated continuous reactor for the synthesis of organic compounds, which uses online mass spectrometry (MS) for reaction monitoring and product quantification, is presented. Quantitative and rapid MS monitoring was developed and calibrated using HPLC. The amidation of methyl nicotinate with aqueous MeNH2 was optimised using design of experiments and a self-optimisation algorithm approach to produce >93% yield.
This note covers work carried out at Leeds University with co-workers from Durham University in the area of flow chemical synthesis using the expression CMS (Advion, Ithaca, NY). Two different reactions are described.