Dr Dirk Kuschneck of Microinnova shares some case studies of using flow in fluorination
Continuous manufacturing as a tool for early- and late-stage fluorination of pharma & agro actives
Dr Dirk Kuschneck of Microinnova shares some case studies of using flow in fluorination
Incorporating process intensification strategies and continuous modes of operation in fluorination processes has been of great interest in recent years , especially in the pharmaceutical and agrochemical sectors . This can be attributed to highly reactive and toxic species hold-up minimisation , excellent mixing and / or heatexchange capabilities , as well as the implementation of production plant encapsulation techniques to mitigate potential process-related issues .
In the pharmaceutical industry , approximately 30 % of newly developed small molecule APIs contain at least one fluorine molecule , primarily due to the favourable solubility properties of fluorinated compounds in blood . In the agrochemical sector , approximately 50 % of newly developed AIs incorporate at least one fluorine molecule .
By incorporating fluorine into the molecular structure of the active , properties such as uptake into the plant or providing a long-term effect are enhanced . Recently , more and more fluorine has been added to actives in the pharmaceutical and agrochemical industries , but at the cost of their ultimate biodegradability .
PFAS issues
Currently , per- and polyfluoroalkyl substances ( PFAS ) – sometimes referred to as ‘ forever chemicals ’ - are a hot topic . They have been detected basically everywhere on our planet , from deep in the sea to human brains .
Project leader Franz Strauss and other members of the Microinnova team
The long-term effect of exposure to PFAS is unknown and governments worldwide are discussing possible bans .
PFAS are all substances with very high fluorine content . The principal definition of PFAS is that at least one carbon atom needs to be fully fluorinated . An example for this might be a R-CF 3 or R-CF 2 -R moiety within the molecule .
With its technology , Microinnova provides selective fluorination only to specific positions in the molecule , by which the good properties of the fluorine can be provided to the active , while maintaining degradability . While we are of course aware of the issues arising from the use of PFAS , we are confident that certain applications benefit greatly from the presence of fluorine . Especially in critical applications , such as cancer treatment , fluorinated APIs are stateof-the-art and have been proven to save lives .
Fluorination strategies
Two distinct strategies employed for the synthesis of fluorinated APIs are early-stage and latestage fluorination . The distinction between these routes lies in how they use fluorine .
Early-stage fluorination involves the incorporation of fluorinated building blocks , obtained from inexpensive reagents , during the initial phases of synthesis . In contrast , late-stage fluorination requires the use of highly selective reagents to introduce fluorine into the final API structure .
44 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981