Green Engineering for Process Safety and Benign Environment

This Keynote will create the context for Green Engineering and how it can accelerate the implementation of new emerging technologies driving Sustainability. The talk would also highlight how the 12 Principles of Green Engineering create a framework for chemists and chemical engineers for design of products and processes that are inherently safe for human beings and for the environment.

As we consider the principles of green chemistry, there are clear advantages of electrosynthesis in replacing the use of stoichiometric amounts of oxidizing agents and reducing agents in terms of minimizing waste and atom economy. However, electrochemistry is not known for selectivity. This paper will discuss the use of biocatalysts for improving the selectivity of organic electrosynthesis to minimize or eliminate the need for downstream separations and purifications. Specifically, we will discuss the main challenge of biocatalysis of economical NAD/NADP cofactor regeneration and provide strategies for electrochemical cofactor regeneration using diaphorase immobilized in cobaltocene and methyl viologen-based redox polymers. Secondly, we will discuss strategies for wiring monooxygenase to electrode surfaces for eliminating the need to add cofactor to the system. The strategy of eliminating the need for cofactor decreases costs, but decreases waste production and atom economy. We will show examples of single step reductive transformations and one-pot electrosynthesis with catalytic cascades. The paper will show strategies for translating lab-scale technology to electrochemical batch and flow reactors with a focus on reactor design and engineering.

Industrial nitrobenzene manufacture is dominated by mixed-acid (HNO3/H2SO4) technology, which introduces substantial corrosion, spent acid recovery and management, and thermal runaway risk. We report the development and predictive scale-up of a continuous, sulfuric-acid-free benzene nitration process using only commercially available 68 wt% nitric acid in titanium reactors.
Experiments conducted in the Amar MicroFLO platform across HNO3:benzene molar ratios from 1:4 to 5:1, temperatures from 50–120 °C, residence times of 0.25–5 minutes, and reactor volumes of 5–100 mL demonstrate >99.5% selectivity to mononitration. Dinitration products and phenolic byproducts are undetectable by gas chromatography and are observed only at ppm levels by mass spectrometry. Reactor pressure drop, heat transfer coefficients, organic–aqueous mass transfer coefficients, and residence time distributions were independently characterized. A mass-transfer-coupled kinetic model assuming first-order dependence on benzene and nitric acid in the aqueous phase provides an excellent fit across all operating conditions (R2 ~ 0.96). The resulting framework enables seamless scale-up in the MicroFLO reactor and first-principles scale-up in tubular Amar CorFLO reactors using independently developed transport correlations.
The process is inherently safer than mixed-acid systems. Reaction-induced dilution reduces nitric acid concentration below 60 wt%, rendering the aqueous phase effectively non-reactive and providing self-limiting thermal behavior. Elevated temperature excursions therefore suppress rather than accelerate reaction. Any breach into the hot-water utility shell results in immediate quenching rather than escalation. Elimination of sulfuric acid removes the regeneration loop, reduces acid inventory, and enables corrosion-resistant titanium construction with extended asset life.
Nitric acid is fully recycled via reconcentration, reaction-generated water is reused for organic washing, and approximately 50% of the concentration duty is recovered from the heat of nitration. The resulting non-raw-material operating expenses are structurally lower than those of the established NORAM and KBR technologies while maintaining stoichiometric raw material efficiency. By eliminating sulfuric acid, integrating heat recovery, recycling nitric acid, and designing for self-limiting reactivity, this process operationalizes core principles of green chemistry and green engineering at an industrial scale.

Biocatalysis offers significant opportunities to reduce process mass intensity, lower energy demand, and eliminate hazardous reagents by enabling highly selective transformations under mild conditions. Several established industrial examples, including antibiotics, synthetic esters, and chiral amines, demonstrate that biocatalytic processes can deliver both environmental and economic advantages at commercial scale. Importantly, these successes were not enabled by catalyst performance alone, but by deliberate engineering decisions addressing separation, inherent safety, material efficiency, and lifecycle impacts consistent with the 12 Principles of Green Engineering.

Biocatalytic processes succeed at scale when their intrinsic strengths (exceptional selectivity, operation at moderate temperature and pressure, and the ability to enable multi-step transformations without intermediate isolation) are deliberately leveraged to meet commercialization constraints. In practice, selectivity improves product purity and reduces downstream separation burden and solvent consumption, lowering process mass intensity and improving economics. Operation at moderate conditions reduces energy demand, expands materials-of-construction options, improves safety margins during scale-up, and increases compatibility with existing capital infrastructure. Telescoping sequential transformations within a single reactor can reduce intermediate isolation, solvent exchange, and additional unit operations, lowering capital intensity and simplifying plant layout.

Translating these advantages into commercial reality requires biocatalysts engineered not only for activity, but for durability under industrial conditions. High total turnover numbers reduce catalyst cost contribution and reactor downtime, while robustness to process variability preserves catalyst value and plant performance. Because biocatalytic processes often operate at lower intrinsic reaction rates than traditional heterogeneous catalysis, achieving competitive space–time yields requires tolerance to high substrate and product concentrations, mitigation of product inhibition, and integration of mass transfer with reactor design. Addressing these constraints through coordinated enzyme engineering, immobilization optimization, materials design, and process development is central to expanding commercial adoption.

The advantages of synthetic photo-chemistry for more efficient, greener synthesis are well known, but the challenges of scale-up in batch have limited its adoption. Recent advances in flow chemistry have lead to the design of reactors that can enable robust scale-up, achieving similar kinetics and conversion to lab-scale experiments. This talk will present the principles behind scale-up of photo-flow to address engineering challenges. Case studies exemplifying key features of reactor design based on different chemistries will be discussed.

A cost-effective, atom-efficient synthetic route to memantine hydrochloride has been developed by replacing the traditional bromination-formylation sequence with an acylation strategy. Conventional bromination of 1,3-dimethyladamantane (1,3-DMA) is corrosive, expensive, and difficult to scale, prompting the development of a new process in which 1,3-dimethyladamantane reacts with sulfuric acid and acetonitrile to form the N-acetyl memantine intermediate. Although the batch acylation is highly exothermic (ΔT_ad = 229.77 °C; ΔH_r = -1002.80 kJ/mol), a novel flow-batch hybrid method enables safe thermal management by performing the reaction in a flow reactor at 40 °C, followed by a short batch hold to provide additional residence time. The intermediate is subsequently isolated in flow-batch hybrid mode, delivering >99% purity and 90% yield. This is the first reported flow-batch hybrid synthesis of N-acetyl memantine, reducing the reaction exothermicity to manageable levels (ΔT_ad = 28.4 °C; ΔH_r = -39.9 kJ/mol), improving safety, and enabling industrially viable throughput (75 g/h). The process significantly lowers production costs ($165/kg) and enhances atom efficiency, offering a scalable, sustainable route to memantine hydrochloride.

We, as a society, have recently embraced the concept of systems thinking. And yet much of our infrastructure continues to inhibit the realization of true systems design. Our reductionist approach, and history of creating academic silos, continues to inadvertently suppress the full embracing of thinking in systems. This presentation will discuss some possible pathways to address these silos using noncovalent derivatization and mechanochemistry as illustrative examples.

Many emerging Green & Sustainable Chemistry inventions are unable to see the light of of the day and make real impact at commercial scales, on process safety and environmental pollution, due to various contraints especially related to engineering aspects. This panel discussion would focus on some of the emerging Green & Sustainable Chemistry technologies like Bio-catalysis, Mechano-chemistry, Electro-chemistry, Photo-chemistry, Flow Chemistry, etc and the role of engineering in successful commercialization of these technologies. The panel discussion would cover the role of reactor design, the need for specialized equipment or other chemical engineering dimensions for effective scale-up of these emerging technologies.