Page 189 - CW E-Magazine (22-4-2025)

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The cyclical nature of batch pro- terised by precise thermal control and elevated pressures or temperatures. ments in process intensifi cation, conti- solve gases directly into liquid streams nuous insight into reaction conversions
cesses also leads to periods of the virtual elimination of hotspots, European producers have demon- nuous fl ow technology delivers no- under controlled pressures, averting and impurity levels, ensuring swift
downtime between batches, further thus signifi cantly reducing runaway strated up to 10-15% higher yields in table improvements in process safety large gas pockets that can accumulate adjustments that maintain consistent
impacting overall productivity. hazards. Moreover, short diffusion aromatic nitrations by running them at by virtue of its fundamental operating and ignite under unstable conditions. product quality. Automated feedback
 Greater environmental impact: The paths in microreactors enhance mass 120-130°C under pressure, a condition principles. When pumps cease, reagent flow loops holding stoichiometries, tempera-
potential for side product formation transfer, which in turn improves reac- that is typically unsuitable for large halts, causing pressure to dissipate and tures, and residence times at optimum
due to poor control, coupled with tion kinetics and ultimately increases batch reactors. Furthermore, fl ow set- A key safety advantage stems from effectively containing any hazardous levels further reinforce product unifor-
the generation of larger volumes throughput. This advancement is parti- ups can handle unstable intermediates – the small active volumes inherent in gases still in the system. This design mity and stave off batch-to-batch vari-
of waste and the higher energy cularly noticeable in catalytic hydro- including diazonium salts and organo- fl ow reactors. Even in the event of principle has seen particular success ability. This real-time control not only
demands, results in a greater environ- genations, where packed-bed or mono- lithium compounds – by producing power or cooling failure, only milli- in the agrochemical sector, where it enhances effi ciency but also provides
mental impact associated with tradi- lithic fl ow reactors have outperformed them in small volumes and immedi- liter-quantities of reactive substances lowers the risks commonly associated an early warning system for potential
tional batch manufacturing. their batch counterparts by delivering ately consuming them downstream, are typically present, which dramati- with ammonia or hydrogen usage. safety deviations.
20-40% higher productivity. Lonza’s removing the necessity for potentially cally lessens the severity of potential Additionally, inline quenching can be
The transformative potential of continuous hydrogenation approach perilous storage. Merck’s integration incidents. The pharmaceutical major integrated to eliminate or neutralize left- Modularity is another key advan-
fl ow technology and continuous for agrochemicals, for instance, im- of microreactors to perform diazotiza- Novartis leveraged this inherent safety over reactive species, as exemplifi ed tage of continuous manufacturing.
manufacturing proved productivity and minimised tion, for example, drastically lowered advantage when it transitioned nitra- by the immediate destruction of azides Scaling capacity often proceeds by
In response to the limitations of hydrogen gas buildup risks by cleverly the probability of diazonium salt de- tion steps from batch to microreactors, in tetrazole synthesis. Such measures numbering-up multiple smaller fl ow
batch processing, fl ow technology employing tube-in-tube reactors. composition and improved yields by resulting in a reclassifi cation to lower protect both personnel and the sur- modules rather than constructing an
and continuous manufacturing have mitigating side reactions. hazard categories that translated into rounding environment. entirely new large-scale reactor. This
emerged as powerful and transfor- Continuous fl ow reactors also simpler and more cost-effective safety approach allows for more agile market
mative alternatives for the chemical allow exceptional precision in control- A central tenet of process intensifi - protocols. Continuous manufacturing: an inte- response and simplifi es fault isolation
industry. By conducting chemical re- ling key reaction parameters such as cation is the integration of reaction and grated approach to intensifi cation if a single module fails, minimising
actions in a continuous stream within temperature, pressure, residence time, separation in a seamless continuous Moreover, continuous systems and safety disruption to the entire production line
confi ned channels, typically in micro- and stoichiometry. The ability to modify sequence. Inline liquid-liquid or mem- excel in controlling hazardous reac- Continuous manufacturing strate- and containing potential incidents.
reactors and millireactors, these tech- these conditions in real time through brane extraction can remove undesir- tions such as nitrations, sulphonations, gies amplify the safety and effi ciency The industry has documented substan-
nologies offer a paradigm shift in automated pumps and inline analytical able byproducts as they form, thereby and hydrogenations due to the rapid gains inherent in fl ow chemistry by tial capital and operational savings
how chemical transformations are tools, including pH, UV-Vis, and FTIR shifting reaction equilibrium to favour heat removal they offer. The capability merging multiple processing and puri- due to these effi ciencies. Although the
executed, leading to signifi cant enhance- sensors, ensures that reactions remain product formation. Some industries to generate reactive intermediates on fi cation steps into a single, uninterrup- upfront costs for continuous systems
ments in both process intensifi cation and within tightly prescribed limits. These have gone a step further by coupling demand, such as azides or phosgene, ted pipeline. This integrated paradigm, can sometimes be higher compared to
safety. fi ne-tuned controls suppress unwanted continuous reactors with crystalliza- in minuscule quantities effectively often termed End-to-End Processing, conventional batch equipment, many
byproducts, prevent off-spec products, tion stages, enabling direct collection nullifi es storage-related explosion further minimises risks and enhances companies recoup the investment
Flow technology and chemistry reduce material waste, and streamline of purifi ed solids and cutting down on hazards. When integrated with advanced productivity. through reduced waste, lower energy
stand at the forefront of process inten- downstream processing. Pharmaceuti- labour- and time-intensive offl ine iso- monitoring and control technologies, consumption, diminished safety risks,
sifi cation efforts. Microreactors and cal manufacturers have documented lation. By integrating processes, manu- fl ow reactors act as a formidable bar Reduced human interaction with and shorter production cycles. Bayer,
millireactors, characterised by their yield improvements of 15-20% by facturers reduce physical footprints and rier against thermal runaway events. hazardous substances is a signifi cant for instance, reported that a conti-
dramatically enhanced heat and mass shifting sensitive steps such as cyclo- accelerate throughput while simulta- Instruments that constantly track tem- safety benefi t of continuous manu- nuous polymerization line reduced
transfer characteristics due to their dehydrations from batch vessels to neously enhancing product purity and perature and pressure can swiftly divert facturing. With fully enclosed sys- both the plant footprint and total energy
high surface-area-to-volume ratios, microreactors. They have also noted consistency. This streamlined approach or halt reagent feeds if anomalies arise, tems and fewer manual transfer steps, consumption by roughly 20% relative
are central to this advancement. In reduced regulatory burdens, as real- also leads to notably lower Process limiting risk to the immediate region the potential for operator exposure to to their old batch-based system.
these confi ned channels, exothermic time monitoring lowers the chance of Mass Intensity (PMI), as smaller re- of the reactor. Compact fl ow equip- dangerous materials is substantially
reactions such as nitrations and hydro- hazardous accumulations and simpli- actor volumes and continuous reagent ment is also more amenable to second- decreased. The direct coupling of In the broader context, fl ow chemis-
genations benefi t from faster and more fi es process validation. introduction minimise the need for ary containment measures, as it can be reactors and separators also lessens the try and continuous manufacturing
uniform heat dissipation, effectively excessive stoichiometric surpluses, enclosed in fi re- or blast-resistant chances of spillage during transfer, a impart signifi cant economic advantages
mitigating the risk of thermal runaway Process intensifi cation efforts are thus signifi cantly decreasing waste modules, thereby further mitigating common source of accidents in batch by offering stable production rates
episodes that have historically plagued further amplifi ed through the expanded generation. A continuous nitration pro- the fallout of potential incidents. operations. with minimal downtime, improved
large-scale batch operations. process windows that continuous cess, for instance, reduced acidic waste yields, reduced raw material costs, and
reactors enable. While open batch six-fold compared to batch. Flow reactors similarly bolster Continuous manufacturing relies lower waste disposal fees. The shift to
Notable industrial adopters, includ- reactors often operate within conserva- safety when dealing with gaseous re- heavily on comprehensive real-time continuous, intensifi ed processes thus
ing DSM and Lonza, have illustrated tive temperature or pressure thres- Enhancing process safety through agents that are fl ammable or toxic. monitoring via Process Analytical becomes a profi t driver, as safer ope-
the substantial benefi ts of adopting holds to avoid uncontrollable hazards, the adoption of fl ow technology Rather than relying on headspace pres- Technology (PAT). Techniques like rations not only reduce liability and
continuous nitration methods charac- fl ow systems can function safely at Beyond the signifi cant advance- surization, tube-in-tube designs dis- NIR, Raman, and FTIR offer conti- insurance expenses but also frequently

188 Chemical Weekly April 22, 2025 Chemical Weekly April 22, 2025 189

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