In George Orwell’s classic 1945 novella ‘Animal Farm’ the revolutionary livestock develop the slogan “Four legs good, two legs bad” to summarize their views on the farmer and other humans. As the novella progresses, we see that things cannot be simplified so readily, and so I was encouraged by the recent excellent article by Brianna Barbu in Chemical and Engineering News (February 12/19, 2024) showing that the mindset “earth-abundant metals good, precious metals bad” was a similar oversimplification when it came to making homogeneous catalysis greener. It was particularly heartening to see so ..read more

The introduction of bromine into intermediates is a key transformation in the synthesis of pharmaceuticals and other high value materials, due to the reactivity and selectivity it offers for further transformation, over for example the generally cheaper, more common but less reactive chlorinated analogues. Bromine is commonly introduced by one of three reagents: bromine itself (Br2), HBr, or N-bromo-succinimide (NBS), all with or without mild oxidants, although other methods are available (see the ACS Green Chemistry Institute Pharma Roundtable on Brominations for an overview – https://reagent ..read more

Organolithium reagents are powerful and ubiquitous intermediates used extensively in synthetic chemistry both in academic and industrial settings. The stability of these reagents often necessitates generation and rapid processing at cryogenic temperatures: some organolithium species are chemically or configurationally unstable at temperatures above -100°C. An example is the dichloromethyllithium anion generated during the Mattison homologation reaction used in the synthesis of Vaborbactam (Figure 1).1 The need for low temperature generation and processing of the organometallic species stems fr ..read more

In December 2023 Nick Tyrell from ALMAC gave an interesting and timely presentation at our Winer Process Chemistry Conference in Liverpool, UK on the proposed EU ban of all per– and poly-fluorinated materials, including polymers and the fluorinating reagents we use routinely to introduce fluorine or fluorine-containing functional groups into complex molecules. The details of the proposed changes were recently highlighted in the Organic Process Research and Development journal.1 These changes could potentially have a profound impact on the chemical industry (Figure 1) including serious disrupti ..read more

We spoke to chemists at different stages of their careers about their experiences of attending our ‘Chemical Development and Scale Up in the Fine Chemical and Pharmaceutical Industries’ training course. Ben Littler  Ben told us that he had taken the ‘Chem Dev’ course twice as an early career process chemist!  Both courses were held as in-house training events. It was fascinating to hear about Ben’s experiences going back to the start of his career journey! The first time Ben took the course was at AMRI in his first year after finishing his academic career and it was led by Trevor (T ..read more

In my previous blog I referred to changes in learning models for industrial chemists described in an editorial in the Journal of Medicinal Chemistry by Dean G. Brown on ‘Adapting to the Changing Landscape of Biotech-Driven Drug Discovery’ (DOI: 10.1021/acs.jmedchem.3c02035) that I discovered through Derek Lowe’s ‘In The Pipeline’ blog titled ‘The Current Industry Landscape’ on 27 Nov 2023. Another key topic in the editorial was the Importance of biotech mentors for early career scientists.   I was extremely fortunate in my early career where I was mentored at the CDMO by one of my cu ..read more

Derek Lowe’s ‘In The Pipeline’ blog titled ‘The Current Industry Landscape’ on 27 Nov 2023 alerted me to an excellent overview editorial in the Journal of Medicinal Chemistry by Dean G. Brown on ‘Adapting to the Changing Landscape of Biotech-Driven Drug Discovery’ (DOI: 10.1021/acs.jmedchem.3c02035). One thing that struck me as I read both the blog and the editorial was that if I simply replaced terms such as ‘medicinal chemistry’ in my mind with ‘process chemistry’ then this too presented an excellent review of the history of how industrial development chemistry had evolved over my career, an ..read more

If you are working in industry and are responsible for safety, how do you safely scale up a given chemical reaction? How do you tackle issues like heat transfer, gas release, exposure control, waste stream issues and more? The core of any process safety study is a correct description of both heat and gas release associated to the reaction. How can these be determined experimentally and how can data be used to ensure a safe scale-up? Each safety study starts with retrieving relevant safety data of your starting materials and reagents, a good starting point is the ECHA website where a ..read more

When I first started working as an industrial process chemist one of my more experienced colleagues told me that you can only really know how well a process performs until you run it on at least a 5 kg scale. I found that to be good advice but as I developed my skills in the kilo lab that I was able to develop work-arounds for steps in a process that were far from perfect. Got a slow filtration? Grab five large Büchner funnels and do the filtration in parallel! However, when I first went to the pilot plant, I learned the hard way that there was only one filter available and that we were just g ..read more

The resurgence of electrochemistry in medicinal chemistry laboratories has created the demand for the rapid delivery of up to a few kilograms of material by the same methods in order to quickly evaluate whether the candidate molecule is a viable clinical candidate or not. Electrochemical processes have been successfully scaled up to commercial scale using parallel plate reactors, but usually this requires a time-consuming complete redevelopment of the reaction conditions, including the electrode materials. In addition, mass transfer is of critical importance to electrochemistry given that reac ..read more