Design of Novel Chemistries and Processes that Enable Sustainable Chemistry Innovation for Industry and Infrastructure: Part 2

The fine chemical and pharmaceutical industries continue to rely heavily on toxic, petroleum-based solvents in the manufacture of active pharmaceutical ingredients. Their production and disposal have significant environmental consequences, with global output estimated at nearly 20 million metric tonnes annually. Many of these solvents are carcinogenic, neurotoxic, or pose reproductive hazards, creating serious risks to both human health and the environment. This creates a clear need for practical alternatives that reduce hazard and emissions without compromising performance.

In this talk, I will share how we have enabled sustainable routes to two pharmaceutically important reaction classes (Henry and fluorination chemistry) by replacing toxic petroleum-derived reagents and solvents such as dichloromethane, with safer and renewable alternatives. I will show how we combined data science with computational chemistry to enable this. I will also outline our progress in evaluating biorenewable options such as Cyrene as industry-relevant replacements, and discuss the practical considerations required to make these substitutions viable for process development and scale-up.

The widespread use of trifluorotoluene (TFT), a high-volume fluorinated solvent in active pharmaceutical ingredient (API) manufacturing, presents significant environmental and economic challenges. To address these issues, an integrated process for the recovery and reuse of TFT was developed and validated up to commercial scale, demonstrating substantial improvements in solvent sustainability and cost efficiency.
By deploying improved phase separation, we consistently achieved recovery rates of approximately 72%, saving over 62 tons of solvent and $379K in costs in a single campaign. The recovered solvent was analytically demonstrated to meet purity requirements (GC purity >99%) and maintained low moisture content (<500 ppm), supporting direct reuse in subsequent API batches.
Liquid-liquid continuous membrane in-line separator adoption can further enable potential reductions in TFT use and energy consumption, with likely saving of $438K in TFT consumption, over 1,200 kWh of natural gas savings, and lower operating costs across single campaigns.
Additional downstream benefits include reduced hazardous waste generation, enhanced process safety, shortened reaction and handling times, and mitigated environmental and regulatory impacts often associated with persistent PFAS-related solvents.
This case study demonstrates the practical routes and positive outcomes of embedding solvent recycling into pharmaceutical process development, offering a replicable model for sustainable manufacturing. Attendees will leave with insights into the technical approaches, operational benefits, and measurable environmental impacts of solvent recycling, supporting the next generation of green chemistry solutions

Mechanochemistry offers a solvent-minimized, inherently scalable, and functionally tolerant platform for the sustainable construction of C–N, C–O, and C–C bonds in pharmaceutically relevant scaffolds. In this contribution, we showcase an integrated mechanochemical toolbox that replaces several hazardous solution–phase transformations with bench–stable reagents, minimal solvent, and efficient energy input. First, we will highlight a Cu(I)–catalyzed anaerobic oxidation of aryl diazo esters with heterocyclic N–oxides under liquid–assisted grinding, which furnishes 1,2–dicarbonyl systems in high yields at room temperature, displays broad substrate scope, and is readily scaled, while enabling direct downstream conversion into α–ketoamides and active-pharmaceutical-ingredient precursors. We will then focus on a Chan–Lam–type N–arylation of primary sulfonamides with arylboronic acids that delivers mono–N–arylsulfonamides, avoids friction–sensitive oxidants, and significantly improves process safety and green metrics compared to classical solution–based protocols. Finally, we will demonstrate how a bench–stable saccharin-derived dinitro reagent enables rapid, Lewis–acid–promoted mechanochemical nitration to access nitrate esters and nitroarenes with excellent functional-group tolerance and shortened reaction times. Taking together, these case studies will illustrate how coupling mechanochemical energy input with simple copper catalysis and recyclable organic oxidants provides a unified, greener strategy for late–stage functionalization and value-added synthesis, achieving higher molar efficiency, reduced waste, and improved operational safety relative to conventional organic methods.

The realm of nanocrystals has expanded across numerous scientific disciplines, driving innovations that increasingly favor biobased nanomaterials over conventional counterparts. Consequently, demand for bionanomaterials has surged in fields ranging from materials engineering to biomedical science. Among these, chitin nanocrystals have attracted significant attention due to their natural abundance, biodegradability, biocompatibility, and high mechanical strength. These nanocrystals are primarily derived from crustacean shells, insect exoskeletons, and fungal cell walls. Despite the vast global generation of crustacean shell waste, only a small fraction is currently valorized, leaving a largely untapped chitin-rich resource comprising approximately 25–30% of shell biomass.
Conventional chitin isolation relies on harsh acid–alkali treatments; in contrast, we present a cost-effective ionic-liquid-based platform for the direct extraction of chitin nanowhiskers (ChNWs) from diverse biomass sources, enabling sustainable valorization of chitin-rich waste. The extracted ChNWs are subsequently employed as biobased reinforcements in polyamide-6 (PA-6) composites, where strong hydrogen-bonding interactions facilitate efficient load transfer. The primary objective of this study is to systematically evaluate the influence of both biomass origin and ionic liquid chemistry on the structural, chemical, and performance attributes of ChNWs. Precisely, certain key parameters, including purity, aspect ratio, surface chemistry, molecular weight, degree of acetylation (%DA), and crystallinity index (%CrI), are examined as functions of feedstock and IL selection. Furthermore, we simultaneously report the fabrication of PA-6/ChNWs nanocomposite films via a casting and solvent-evaporation method, followed by comprehensive structural (FTIR, pXRD), thermal (TGA), morphological (SEM), mechanical, and rheological (DMA) characterization. This demonstrates the potential of ionic-liquid-processed ChNWs as sustainable, high-performance fillers for lightweight polymer composites.
Overall, our work aims to establish a pilot-scale, economically and environmentally viable process for nanochitin isolation and demonstrate its potential as an advanced reinforcement that can outperform glass-fiber-reinforced plastics while reducing carbon footprint, highlighting its promise for lightweight automotive applications.

Pyrene derivatives are of growing interest owing to their rigid aromatic core, extended π-conjugation, and unique optoelectronic properties. In this study, pyrene-4,5-dione was employed as a key synthetic intermediate to generate a library of novel derivatives, including semicarbazones, thiosemicarbazones, oximes, triazoles, and hydroxyl-triazoles. These compounds were synthesized via condensation and cyclization reactions under mild to moderately elevated conditions and characterized by NMR and LC–MS, confirming successful incorporation of diverse nitrogen- and oxygen-donor functionalities. The resulting derivatives display tunable electronic and structural features, which may influence hydrogen bonding, metal coordination, and redox behavior, thereby expanding their potential reactivity profiles. Beyond synthetic versatility, these pyrene-based scaffolds present opportunities for applications in molecular electronics, fluorescent sensing, and catalysis, as well as in medicinal chemistry, where semicarbazone and triazole motifs are known to impart biological activity. This work demonstrates the utility of pyrene-4,5-dione as a versatile platform for accessing functionally diverse frameworks that bridge fundamental organic synthesis with emerging applications in advanced materials and bioactive compound design.

Solid-acid-catalyzed etherification of glycerol with ethanol generates ethers that are promising low-viscosity solvents for CO2 capture and biomass fractionation. Because water is produced as a coproduct and drives equilibrium toward reactants, hydrophobic catalysts can improve performance by lowering the thermodynamic activity of water near intraporous acid sites. Here, we examine how zeolite framework topology and void polarity influence liquid-phase glycerol etherification. Reactions starting from glycerol or the di-ether intermediate 1,3-diethoxypropan-2-ol (DEP) confirm a reversible network in which monoethyl ether (MEP) is the dominant product, while triethyl ether forms from DEP only at longer times. Initial turnover frequencies (TOFs, per proton) were compared across H-form zeolites, giving the trend H-Beta > H-MFI > H-FAU > H-MOR, an ordering in agreement with prior reports. To decouple framework composition from void polarity, we synthesized H-Beta zeolites with varied aluminum content crystallized in either hydroxide (H-Beta-OH) or fluoride media (H-Beta-F). Fluoride-mediated synthesis yields solids with fewer intraporous silanol defects, reducing void polarity (increasing hydrophobicity) relative to solids synthesized in hydroxide media. Across both mineralizing routes (OH and F), TOFs and apparent glycerol reaction orders showed little dependence on Brønsted acid-site density. TOFs increased with decreasing volumetric water uptake (a proxy for void polarity). Regression of the measured TOFs as a function of glycerol concentration to a Langmuir–Hinshelwood model demonstrated that there were larger intrinsic rate constants for glycerol etherification over H-Beta-F than for H-Beta-OH. Apparent activation energies and enthalpies were lower for H-Beta-F than for H-Beta-OH. Reuse experiments show partial deactivation, but H-Beta-F retains a higher gravimetric rate after reuse than H-Beta-OH. Overall, these results demonstrate that void polarity governs reactivity and stability in glycerol etherification, and that H-Beta-F zeolites are the most active per-site catalysts among the materials studied.

In light of growing concerns regarding the worsening state of the environment, chemists continue to develop green methodologies to reduce the chemcical enterprises impact on the planet. One area of green chemistry that has been underexplored is the combination of established catalytic reactions and green solvent system. Of particular interest are the N-Heterocyclic Carbenes (NHC’s) a versatile class of organocatalysts capable of a variety of carbon-carbon bond forming reactions. However, little research has been done exploring the use of NHCs in environmentally friendly solvent systems. The solvents of choice for the typical model reaction, the benzoin condensation, include dichloromethane, tetrahydrofuran, and methanol. The investigation of the benzoin condensation in newer green and sustainable solvent systems has received much less attention. In our presentation we will describe our work on the reaction and stereoselectivity of the NHC catalyzed condensation reactions in newer green and sustainable solvents.

Linear low-density polyethylene (LLDPE) is a very common material for single-use packaging and consumer goods, but these products often end up in landfills or polluting the environment. Hydrothermal liquefaction (HTL) shows promise as a method of advanced recycling. Using supercritical water, HTL can be used to convert LLDPE into crude oil and natural gas. Above the critical point of water (374°C, 22MPa), the polarity decreases. Water can start to interact with nonpolar polymers like LLDPE as a solvent and reactant to initiate C-C bond cleavage via radical intermediates. This generates a diverse collection of aliphatic, cyclic and aromatic hydrocarbons.
Zeolites are a type of aluminosilicate catalyst commonly used for upgrading crude oil via catalytic cracking. Long chain hydrocarbons can diffuse through these pores and transform into smaller molecules (also known as cracking). The pore system can also act as a “molecular sieve” to select for certain molecular shapes and sizes. One of the most common zeolites for this technique is called ZSM-5 (zeolite Saucony Mobil-5). This zeolite is characterized by a very high Si:Al ratio (usually over 15) which allows for deposition of hydrogen cations within the pore structure. The catalyst therefore acts as a “solid acid” by generating carbocation intermediates to initiate catalytic cracking. In this study, H-ZSM-5 (the protonated ZSM-5 zeolite) is used to catalyze the HTL reaction of LLDPE to lower activation energy and increase selectivity of the oil product towards high value BTEX (benzene, toluene, ethyl benzene, xylenes) compounds.
HTL reactions were conducted in a 30-35 mL stainless steel tubular batch reactor in an inert environment. The optimal condition for uncatalyzed oil production was determined to be 450°C for 2 hours, and the optimal concentration of zeolite catalyst relative to LLDPE weight was found to be 10% by weight (1 gram LLDPE, 0.1 grams H-ZSM-5). At this concentration, oil production was statistically similar but the BTEX concentration in the oil increased from 12% to 28%. Additionally, the total concentration of monocyclic aromatic hydrocarbons (MAHs) increased from 23% to 71%, including BTEX compounds. Continuing work is focused on regenerating the H-ZSM-5 catalyst for multiple catalytic cycles and observing effect of HTL on the zeolite’s pore structure and Brønsted acidity.