A5056977910- Innovative Microfluidic and Catalytic Techniques Innovation
- Microfluidic and Capillary Electrophoresis Applications
- Radical Photochemical Reactions
- Analytical Chemistry and Chromatography
- Process Optimization and Integration
- Advanced Control Systems Optimization
- Asymmetric Hydrogenation and Catalysis
- Chemical Synthesis and Analysis
- Oxidative Organic Chemistry Reactions
- Advanced Photocatalysis Techniques
- Nanomaterials for catalytic reactions
- Electrochemical Analysis and Applications
- Electrocatalysts for Energy Conversion
- Spectroscopy and Chemometric Analyses
- Chemical Synthesis and Reactions
- Carbon Dioxide Capture Technologies
- Catalytic Cross-Coupling Reactions
- NMR spectroscopy and applications
- Neural Networks and Applications
- Chemical synthesis and alkaloids
- Machine Learning in Materials Science
- Coordination Chemistry and Organometallics
- Catalysis and Hydrodesulfurization Studies
- Computational Drug Discovery Methods
- Catalytic C–H Functionalization Methods
University of Graz
2018-2024
Research Center Pharmaceutical Engineering (Austria)
2018-2024
Nawi Graz
2018-2024
National Renewable Energy Laboratory
2023
University of Colorado Boulder
2023
Leibniz-Institute for New Materials
2023
Environmental Energy & Engineering
2023
The University of Adelaide
2020-2023
Imperial College London
2023
University of Strathclyde
2018-2023
In multistep continuous flow chemistry, studying complex reaction mixtures in real time is a significant challenge, but provides an opportunity to enhance understanding and control. We report the integration of four complementary process analytical technology tools (NMR, UV/Vis, IR UHPLC) synthesis active pharmaceutical ingredient, mesalazine. This synthetic route exploits processing for nitration, high temperature hydrolysis hydrogenation reactions, as well three inline separations....
The coupling of a modular microreactor platform, real-time inline analysis by IR and NMR, online UPLC, leads to efficient optimization multistep organolithium transformation given product without the need for human intervention.
Two efficient continuous flow iodoperfluoroalkylation methods are described: using 0.05 mol % perylene diimide (PDI) photocatalyst under 450 nm irradiation or substoichiometric triethylamine 405 irradiation. These enable dramatically elevated productivity versus batch processes. The triethylamine-mediated method is explored mechanistically and in substrate scope. gram-scale synthesis of an active pharmaceutical ingredient side chain also reported flow, via a photochemical followed by hydrogenolysis.
Abstract Oscillatory flow reactors (OFRs) superimpose an oscillatory to the net movement through a reactor. OFRs have been engineered enable improved mixing, excellent heat- and mass transfer good plug character under broad range of operating conditions. Such features render these appealing, since they are suitable for reactions that require long residence times, (such as in biphasic liquid-liquid systems) or homogeneously suspend solid particles. Various OFR configurations, offering...
Although flow photochemistry has significant potential in advancing sustainable processing, there are substantial hurdles to attaining this. Development three key areas over the past 3 years discussed here: 1) light source technology; 2) reactor design; and 3) process understanding intensification. A small number of illustrative examples provide an insight on benefits that can be accessed through advances these areas. More in-depth knowledge experimentation around wavelength dependence...
Dual nickel/photocatalytic C–N couplings are performed with an organic heterogeneous photocatalyst, in oscillatory plug flow reactor. Reaction was complete 20 min residence time, enabling 2.7 g h<sup>−1</sup> throughput and 10-fold catalyst recycling.
Zeolitic imidazolate framework (ZIF) biocomposites show the capacity to protect and deliver biotherapeutics. To date, progress in this research area is based on laboratory batch methods. Now, first continuous flow synthetic method presented for encapsulation of a model protein (bovine serum albumin, BSA) clinical therapeutic (α1-antitrypsin, AAT) ZIF-8. The situ kinetics nucleation, growth, crystallization BSA@ZIF-8 were studied by small-angle X-ray scattering. By controlling injection time...
Autonomous flow reactors are becoming increasingly utilized in the synthesis of organic compounds, yet complexity chemical reactions and analytical methods remains limited. The development a modular platform which uses rapid NMR FTIR measurements, combined with chemometric modeling, is presented for efficient timely analysis reaction outcomes. This tested four variable single-step (nucleophilic aromatic substitution), to determine most effective optimization methodology. self-optimization...
Abstract Flow processing offers many opportunities to optimize reactions in a rapid and automated manner, yet often requires relatively large quantities of input materials. To combat this, the use flexible slug flow reactor, equipped with two analytical instruments, for low‐volume optimization experiments are reported. A Buchwald–Hartwig amination toward drug olanzapine, 6 independent optimizable variables, is optimized using three different approaches: self‐optimization, design experiments,...
Abstract Having identified inconsistencies when repeating literature examples of photochemical transformations and difficulties recreating experimental setups, we devised several criteria that an ideal lab‐scale reactor should achieve. Herein, introduce a versatile photoreactor for high‐throughput screening, preparative‐scale batch reactions continuous processing, all with single light source. The utilizes interchangeable arrays pseudo‐monochromatic high‐power LEDs in range synthetically...
Although continuous flow technology can facilitate the scale-up of photochemical processes it is not yet routinely implemented on production scale in fine chemical industries. This be attributed to additional challenges compared thermal processes, mostly homogeneous irradiation reactor. Here, we detail process bringing a previously developed benzylic bromination, utilizing situ bromine generation, from lab pilot scale. The setup discussed detail, alongside comprehensive risk assessment and...
With ever-evolving light-emitting diode (LED) technology, classical photochemical transformations are becoming accessible with more efficient and industrially viable light sources. In combination a triplet sensitizer, we report the detailed exploration of [2 + 2] cycloadditions, in flow, various maleic anhydride derivatives gaseous ethylene. By use flow reactor capable gas handling LED wavelength/power screening, an in-depth optimization these reactions was carried out. particular, highlight...
Using a Br<sub>2</sub> generator in flow process intensified conditions has been developed for photochemical benzylic bromination on kg scale.
Multivariate analysis is applied to inline benchtop NMR data for a complex nitration in flow. This rapid quantification enables reaction optimization using advanced techniques flow, such as design of experiments and dynamic experimentation.
Automated batch and flow reactors are well-established for high throughput experimentation in both thermal chemistry photochemistry. However, the development of automated electrochemical platforms is hindered by cell miniaturization challenges difficulties designing effective single-pass systems. In order to address these issues, we have designed implemented a new, slug-based platform. This platform was successfully demonstrated C-N cross-couplings E3 ligase binders with diverse amines (44...
An oscillatory flow photoreactor facilitates the use of Bi<sub>2</sub>O<sub>3</sub> as a green and recyclable photocatalyst for ATRA reactions.
Abstract Zeolitic imidazolate framework (ZIF) biocomposites show the capacity to protect and deliver biotherapeutics. To date, progress in this research area is based on laboratory batch methods. Now, first continuous flow synthetic method presented for encapsulation of a model protein (bovine serum albumin, BSA) clinical therapeutic (α1‐antitrypsin, AAT) ZIF‐8. The situ kinetics nucleation, growth, crystallization BSA@ZIF‐8 were studied by small‐angle X‐ray scattering. By controlling...
As remdesivir is the first approved treatment for COVID-19 (SARS-CoV-2), its production likely to be of vital importance in near future. Continuous flow processing has been demonstrated as a key technology manufacturing high-volume active pharmaceutical ingredients and considered use this synthetic sequence. In particular, challenging C-glycosylation pyrrolotriazinamine via metal–halogen exchange was identified transformation with significant potential benefit, exemplified by calorimetric...
In a rapidly changing environment, such as the current COVID-19 pandemic, continuous flow reactors bear potential to increase production of urgently needed active pharmaceutical ingredients (APIs) on demand. synthesis remdesivir, organometallic C-glycosylation step was identified limitation for large-scale production, requiring long addition periods and cryogenic temperatures. Previous studies have focused Grignard-based protocol, but flash chemistry approach, using organolithium reagents,...
Abstract In multistep continuous flow chemistry, studying complex reaction mixtures in real time is a significant challenge, but provides an opportunity to enhance understanding and control. We report the integration of four complementary process analytical technology tools (NMR, UV/Vis, IR UHPLC) synthesis active pharmaceutical ingredient, mesalazine. This synthetic route exploits processing for nitration, high temperature hydrolysis hydrogenation reactions, as well three inline...
Dynamic deracemization processes, such as crystallization-induced diastereomer transformations (CIDTs), offer the opportunity to combine racemization and resolution provide high yields of enantiomerically pure compounds. To date, few these processes have incorporated photochemical racemization. By combining batch crystallization with a flow photoreactor for efficient irradiation, it is possible perform in an effective, scalable yielding manner. After applying design experiment (DoE)...
Using dynamic flow experiments, a predictive reaction model can be rapidly fitted. Here, up to five different input parameters were varied simultaneously, allowing rapid exploration of design space.