Reaction Chemistry & Engineering最新文献

The scale-up of photoreactions posses challenges due to the non-linear coupling of the radiation field with reaction kinetics and mass transport. A knowledge-based scale-up requires a sufficiently detailed theoretical description of these processes. In this work, a transient, two-dimensional photoreactor model is proposed and used to systematically investigate mass transport limitations in photoreactors, including the effect of transversal mass transport through static mixers and the self-shading effect of the studied homogeneous photoisomerization of a spiropyrane. Simulation results of the proposed photoreactor model indicated that mass transport along the direction of light has a major impact. The transversal dispersion would be increased by a factor of 6 by the installation of static mixers, which would allow for a 1.27 fold increase in conversion in an up-scaled photoreactor. A shrinking of the reaction zone was identified when increasing the light power, eventually limiting the reactor performance. Furthermore, a model-based scale-up study emphasized the importance of mass transport for scaling photoreactors.

Accurate kinetic models for enzyme catalysed reactions are integral to process development and optimisation. However, the collection of useful kinetic data is heavily dependent on the experimental design and execution. In order to reduce the limitations associated with traditional statistical design and manual experiments, this study introduces an integrated, automated approach to identifying kinetic models based on model-based optimal experimental design. The immobilised formate dehydrogenase of Candida boidinii catalyses the enzymatic reduction of NAD⁺ to NADH and is used as a model system. Continuous collection of UV/Vis data under steady-state conditions is employed to determine the kinetic parameters in a packed bed reactor. Automation of the experimental work was utilised in Python to compensate for the need for more time-consuming data collection. A completely automated closed-loop system was created and appropriate kinetic models for anticipating process dynamics were identified. The automated platform was able to identify the correct kinetic model out of eight candidate models with only 15 experiments. Further extension of the design space improved model discrimination and led to a properly parameterized kinetic model with sufficeintly high parameter precision for the conditions under examination.

With the current global economy developing at a rapid pace, research into lithium-ion batteries has become a focal point in many major areas. Lithium iron phosphate, also known as LiFePO₄ or LFP, is one of the most promising cathode materials for commercial lithium batteries. Its advantages include low cost, environmental friendliness, long cycle life, good thermal stability, and more. Its high-rate charge–discharge capability is limited by its low electronic conductivity and lithium ion diffusion coefficient. Thus, this work describes the structural features of LiFePO₄ cathode materials, focuses on their modification (coating, ion doping, morphological control methods), and concludes by anticipating the direction of future research in this field.

In this study, the synthesis of aroma esters by the direct esterfication of carboxylic acids with aromatic alcohols mediated by lipase B from Candida antarctica encapsulated in a sol–gel matrix in a solvent-free system is presented. Vacuum was used in order to remove the resultant water. The reaction parameters were optimized by factorial design experiments considering four factors (acid excess, temperature, vacuum and time) on two levels. As a result, the conversions were significantly increased (for example, from an isolation yield of 49.4% to 94.3% for cinnamyl butyrate). A semi-preparative experiment was further set up for cinnamyl butyrate preparation. The green chemistry metrics, such as the E-factor of 4.76 and mass intensity of 6.04, demonstrated that the newly developed enzymatic process is suitable for industrial application based on green chemistry principles.

Photochemical and photocatalytic reactions are a powerful emerging tool in the green synthesis of organic molecules. In contrast to thermochemical reactions, they promise greater energy efficiency, milder reaction conditions, and a decrease in the number of synthesis steps. Unfortunately, conventional batch photochemical systems are not inherently scalable, making translation to industrial applications challenging. Fundamentally, this is most clearly attributed to the penetration depth of light, as constrained by the Beer–Lambert relationship: as the size of the reactor is increased, the depth of light penetration into liquid medium decreases exponentially. Small-diameter plug flow reactors with external illumination have recently been employed industrially to 1) transition photochemistry from batch to continuous flow, and 2) overcome light penetration challenges by employing millimeter-scale optical paths; however these often present with substantial pressure drops and scalability challenges. In this work, a fixed bed reactor is packed with wireless μLEDs (μLED-PBR) and engineered to scale the oxidation of α-terpinene using a homogeneous rose-bengal photosensitizer. Utilizing μLEDs as packing allows for internal volumetrically scalable illumination from 250 or 500 μLEDs. Not only is the μLED packing efficient at delivering photons, but it also statically induces turbulence and mixing of the biphasic streams within the reactor. Unlike tubular plug flow reactors, the μLED-PBR design is volumetrically scalable. During operation, a co-current trickle flow regime was established with a 29 μm liquid film flowing over the μLEDs. In stark contrast to those typical in small channel tubular flow reactors, the packed bed experienced negligible hydrodynamic pressure drop penalties. The photochemical space time yield of the reactor normalized to the power consumption for the μLED-PBR was three orders of magnitude greater than other externally illuminated thin film flow reactors for the same chemistry: 1411 mmol W⁻¹ per day compared to 1.34 mmol W⁻¹ per day.

The wide-scale production of nanomaterials would benefit from scalable synthetic methods. One class of promising nanomaterials consists of a core@shell structure in which one type of material is used for the core and a second material is grown on the surface to produce a shell. Although these materials are commonly realized in batch, core@shell structures have not yet been widely translated to scalable manufacturing processes. In this work, we investigate the continuous flow synthesis of Au@Ag core@shell nanomaterials using sequential jet-mixing reactors (JMRs). Connecting the two JMRs overcomes challenges with particle instability when the processes are separated. Using synthesis conditions typical for batch methods in the JMR resulted in a non-uniform particle size distribution. Through investigating the synthesis conditions of the Au core, the key parameters affecting the synthesis of well-defined nanoparticles are identified as the concentration of the reducing agent and the inclusion of bovine-serum albumin (BSA) to limit particle aggregation. The concentration of the reducing agent is adjusted to achieve a high yield of Au NPs. The adjusted concentration enabled continuous synthesis of Au@Ag core@shell nanoparticles using BSA as the stabilizing ligand in a dual jet mixing reactor system. Overall, this work provides insights on integrating sequential processes for the synthesis of core@shell nanomaterials.

A focus on environmental sustainability is important in selection of our commercial drug substance manufacturing processes. During clinical development of a bispecific T-cell engager (BITE) molecule we developed two processes to manufacture this important biologic: (1) a stirred tank process and (2) a continuous manufacturing process. We will describe the challenges and opportunities of developing and producing this novel biologic modality, while also minimizing the environmental impact. We will highlight the metrics and methods used to measure and improve the environmental performance of the processes, such as carbon emissions, water consumption, waste generation, and energy efficiency. The benefits of adopting a life-cycle management approach and leveraging continuous manufacturing technologies to enhance the sustainability of the process during development will be discussed and the results compared to the stir tank process to enable the identification of the optimal process for manufacturing of this innovative BITE molecule.

Kinetic analysis of the Claisen rearrangement of allyl phenyl ether (APE) to 2-allylphenol was conducted in pressurized N-methylpyrrolidone (NMP) at various temperatures from 240 to 280 °C using an automated flow reactor. Rapid inline analysis using a compact near-infrared (NIR) spectrometer coupled with a flow rate ramp as a reciprocal function of the experimental time allowed high-density data acquisition (900 points in 15 min) of the conversion of APE over residence times ranging from 0.8 to 10.3 min. Inline NIR monitoring was also employed to measure the residence time of the NMP solution in the reactor. The residence time was shown to decrease by 26% with increasing temperature from 20 to 300 °C due to the thermal expansion of the solution. The APE conversion exhibited first-order kinetics with an activation energy of 137 ± 1 kJ mol⁻¹ and a pre-exponential factor of 7.3 × 10¹⁰ s⁻¹. The result of the flow rate ramp experiment was consistent with that of the temperature ramp experiment, while the latter gave a continuous Arrhenius plot in a wider temperature range from 230 to 290 °C. The rate constant in NMP was found to be 10 and 1.5 times smaller than those reported in subcritical water and alcohol solvents, respectively.

This study reports efforts toward the integrated advanced manufacturing of the anti-narcoleptic drug modafinil. It showcases a holistic approach from flow synthesis to purification via continuous crystallization. The integration strategy included a necessary optimization of the reported flow synthesis for modafinil, enabling prolonged operation and consistent crude quality. The reactor effluents were subsequently processed downstream for purification utilizing two single stage mixed suspension mixed product removal crystallizers. The first stage was an antisolvent cooling crystallization, providing refined modafinil with >98% yield. The second cooling crystallization delivered crystalline modafinil with >99% purity in the required polymorphic form I suitable for formulation.