Continuous manufacturing has received increased attention in the last two decades. The growing number of continuous processes is largely driven by the fact that flow chemistry opens up the possibility to access novel synthetic routes, perform otherwise dangerous chemistry in a safe way, create automated processes which require minimal human intervention¹
Flow chemistry expertise
Since its foundation, ComInnex built up significant expertise in various aspects of flow chemistry. Our early efforts focused on continuous flow hydrogenations to generate novel 3D structures with high Fsp3 characteristics. Using our hydrogenation capabilities, in a collaboration project with three major pharmaceutical partners, we produced >43,000 novel compounds over 3 years, ComInnex designed 635 novel scaffolds and produced 226 libraries.
More recently, our flow chemistry R&D activities target the development of automated and photochemical processes.
What are the potential benefits of flow chemistry?
- Precise control of reaction parameters (temperature, reaction time, pressure) and reagent dosing
- Can lead to enhanced selectivity and yield
- Short lived (t1/2 = seconds, minutes) intermediates can be utilized in microreactors
- Stoichiometric dosing of gaseous reagents can lead to increased safety, selectivity and overall a greener process
- Increased safety during handling of hazardous reagents
- In situ reagent generation (ie. small chemical inventory of the hazardous substance)
- Precise dosing of gaseous reagents under pressurized conditions
- No head space
- Simple work-up using packed bed systems (ie. no need for catalyst filtration)
- Process intensification thanks to the increased parameter space (ie. combination of high T / high p conditions can shorten the reaction time)
How can we support your R&D team?
- Route scouting using continuous flow technology
- Feasibility studies and process demonstration
- Process optimization and intensification
- Heterogeneous catalyst screening (>50 catalysts on stock, mostly for hydrogenations)
- Production of libraries or single compounds from mg to hundred-gram quantities
Some reaction types and technologies where we built significant expertise:
- Hydrogenations and deuterations
- Hydrogen isotope exchange reaction
- Organometallic chemistry (organozinc chemistry and C-C coupling reactions for C(sp)2-C(sp)3 bond constructions)
- Diazomethane chemistry
- High T / high p chemistry (heteroaromatic ring synthesis, amination, esterification)
- Flash vacuum pyrolysis (Gould Jacobs reaction and similar thermal cyclisations)
In-house available instrumentation:
- H-Cube Pro – continuous flow hydrogenations from mg to g scale
- Phoenix Flow Reactor – for homo (coil reactor) and heterogeneous (packed bed reactor) high temperature chemistry up to 450°C and 100 bar
- H-Genie hydrogen generator coupled with Phoenix Flow Reactor – for low kg hydrogenations
- Syrris Asia – multipurpose flow reactor from mg to multi-gram synthesis. Includes low and high temperature modules, multiple inlets for chip and coil reactors, pressure controller, reagent injector.
- ThalesNano’s PhotoCube photoreactor
- Custom made reactor configurations (e.g. for photochemistry, diazomethane chemistry) are utilized when needed.
- Syringe, HPLC and peristaltic pumps
- Mass Flow Controller –for precise gas dosing
- Liquid-liquid/liquid-gas separator
- Injectors, mixers, polymer (PTFE, PEEK, PFA, FEP) and stainless-steel tubing in multiple sizes
- Flash vacuum pyrolysis
¹a) M. P. Plutschack, B. Pieber, K. Gilmore, P. H. Seeberger Chem. Rev. 2017, 117(18), 11796-11893; b) A. Gioiello, A. Piccinno, A. M. Lozza, B. Cerra J. Med. Chem. 2020, 63(13), 6624-6647.