Reaction Chemistry & Engineering最新文献

Continuous flow crystallization is an attractive mode of operation, due to its ability to generate consistent product quality while requiring a smaller footprint and lower production costs than its batch counterpart. We present a novel combination of a custom/in-house automated continuous crystallization platform integrated with self-optimization algorithms. We demonstrate the automated optimization of continuous crystallization of nirmatrelvir (PF-07321332), one of the active ingredients in Paxlovid™, a potent, selective, and orally bioavailable inhibitor of SARS-CoV-2 M^pro. The continuous crystallization platform consists of three mixed suspension mixed product removal (MSMPR) crystallizers in series and includes an in-house designed automation user interface integrated with lab equipment. The platform also has an iterative design of experiments (DoE) based on mixed-integer nonlinear programming (MINLP) self-optimization algorithms. We implement automated controls for the lab equipment, including a flow sonication cell as the nucleation device, feed pumps, temperature controller units (TCUs), thermocouples, pressure sensors, stirrers, and coriolis mass flow meters. We enable integration of variety of in situ process analytical technologies (PATs) via open platform communications unified architecture (OPC UA), including Mettler Toledo ParticleTrack™ with FBRM® (Focused Beam Reflectance Measurement) technology and Blaze™ Metrics imaging probe for the data visualization and real time process understanding.

In the past few years, there has been a prominent surge in the exploration of the synthesis of imidazole derivatives in synthetic organic chemistry. This growing interest arises from the wide range of potential applications offered by these compounds across various fields, encompassing industrial chemistry, pharmaceuticals, and medicinal chemistry. This study demonstrates an innovative synthesis of four-component eutectogels (ETGs), in particular ETG-Zr⁴⁺, for the production of imidazole derivatives. The ETG-Zr⁴⁺ catalyst was characterized using FT-IR spectroscopy, SEM, TGA, and XRD, demonstrating its potential as a sustainable catalyst for the synthesis of poly-functionalized imidazole derivatives. The application of ETG-Zr⁴⁺ as a catalyst afforded 1,2,4,5-tetraphenyl-1H-imidazole derivatives in 70–92% yields and 2,4,5-trisubstituted imidazole derivatives in 61–76% yields. Notably, the catalyst exhibits the advantage of reusability and promotes eco-friendly approaches via a one-pot, multi-component reaction pathway.

The present study aims to develop a natural insect-repellent paint formulation derived from plant-based materials with UV absorption and antibacterial properties. Mentha piperita L. (peppermint) was employed in this study to prepare water extract and zinc nanoparticles. Its absorption in vacuum UV (200–400 nm) demonstrated its property of UV absorption, particle size analysis (less than 100 nm with 10% abundance of 20 nm) confirmed the formation of nanoparticles, and FTIR analysis substantiated the presence of phytochemicals and zinc interaction after composite formation with the plant material (3393.7 and 3304.3 cm⁻¹ = phenolic, 2927.8 cm⁻¹ = aliphatic, 2137.6 cm⁻¹ = aromatic, 2089.2 cm⁻¹ = aldehydes and ketones, 1623.3 cm⁻¹ = alkene). Mentha nanoparticles were added to paint formulations (plastic emulsion water based) to get UV absorbent, bacteriostatic and mosquito repellent coating solutions. The antimicrobial activity was assessed over 360 days at different intervals, demonstrating the significant antibacterial activity of the formulated paints (180 days with Mentha as compared to 7 days without the biocide). A comprehensive evaluation of paint color revealed a significant color change after the addition of plant based synthesized materials. Aedes aegypti mosquitos were used to evaluate the anti-mosquito activity of the formulated paint, and it was found to be 64.2% more efficient compared to non-biocidal formulations.

Zirconium-carboxylate metal–organic frameworks (MOFs) of isoreticular crystal morphologies and contrasting pore sizes are examined to understand the relative influence of linker size (UiO-67 vs. UiO-68) and secondary metal incorporation in photocatalytic aqueous pollutant degradation. Here, iron (Fe) is chosen given its prevalence in wastewater treatment literature and applications, resulting from its low toxicity and ability to activate benign oxidants. UiO-67 with Fe incorporated (Fe-UiO-67) via incipient wetness impregnation demonstrates reduced band gap energy relative to the UiO-67 parent and higher apparent photocatalytic degradation under UV light toward methylene blue dye using hydrogen peroxide (H₂O₂), with catalyst mass-normalized pseudo-first order rate constants of 6.8 ± 0.5 g⁻¹ ks⁻¹ and 2.0 ± 0.3 g⁻¹ ks⁻¹, respectively. While structural characterization via X-ray diffraction remains unperturbed for Fe-UiO-67 before and after reaction, some Fe leaching is evident, as indicated by recharge experiments in the filtrate. Synthesized UiO-68, which possesses increased pore size, also has reduced band gap energy resulting in higher UV-light activation than UiO-67 (pseudo-first order rate constant of 3.5 ± 0.4 g⁻¹ ks⁻¹). Further, UiO-68 demonstrates high stability and exhibits a higher productive H₂O₂ utilization fraction than either of the UiO-67 catalysts. Together, this work clarifies the relative influence of linker modulation and active metal incorporation in UiO-MOFs for pollutant degradation and aqueous applications broadly.

Joule-heated reactors could drive high-temperature endothermic reactions without heat transfer limitations to the catalyst and with high energy efficiency and fast dynamics under suitable conditions. We use 3D computational fluid dynamics (CFD) to investigate the power distribution, temperature field, and flow patterns in continuous steady-state and rapid-pulse Joule heated reactors with carbon fiber paper as the heating element. The model is in good agreement with published experimental data. We demonstrate flow recirculation under typical conditions and derive criteria for their suppression. We showcase rapid (seconds or shorter) and uniform heating to very high temperatures (>1500 °C) with minimal heating of the flowing gas, which could reduce undesired gas-phase chemistry. A simple energy model indicates that a high applied voltage and heating elements of high electrical conductivity and low volumetric heat capacity accelerate heating. We report heat transfer enhancement during rapid pulsing, a form of process intensification enabled by dynamic operation.

Generative chemistry, which uses computational approaches to explore large chemical spaces, has gained considerable popularity in identifying potential lead candidates for drug discovery. However, a challenge with these methods is the lack of consideration of the synthetic feasibility of the generated molecules. This challenge can be addressed using compound generation and virtual screening approaches in combination with computer-aided synthesis planning (CASP) tools. However, the resulting synthesis effort may still be too costly in practice. To overcome this challenge, we present a method to generate a comprehensive set of compounds that effectively cover the chemical space of interest with minimal synthesis effort. The concept of using CASP systems for multi-compound optimization has been discussed previously. The approach presented in this paper goes beyond this and supports an efficient exploration of the chemical space. The goal is to select a small set of candidates (e.g. 25–50) from a larger pool of e.g. 500 candidates that can be synthesized in a few steps, while ensuring high diversity and broad distribution in chemical space. In this paper, we present an approach that effectively achieves both goals.

Monoacylated diamines are common building blocks for numerous active pharmaceutical ingredients. However, the synthesis of these compounds often requires selective protection/deprotection steps, complex catalysts or harsh reaction conditions, leading to waste and poor atom economy. Here, we present a green and efficient procedure for the monoacylation of symmetrical diamines in a microreactor using acyl imidazole as an acyl donor. Taking the advantages of the microreactor, monoacylated diamines were synthesized with superior selectivity under mild conditions and short residence times. The wide substrate scope and selectivity of this continuous flow monoacylation process were confirmed through the synthesis of 20 pharmaceutically relevant amides. Moreover, the application of the monoacylation process in the preparation of antidepressant drug befuraline was achieved, demonstrating the value of this approach for pharmaceutical synthesis.

A series of heterogenized NHC–Pd catalysts were developed to address the high economic cost of C–H functionalizations resulting from the poor recyclability of transition metal catalysts. The catalytic activities of the obtained solid hypercrosslinked catalysts were studied in C–H acetoxylation, iodination, and nitrosation.

Optimization is gaining huge attention in industries like pharmaceuticals, fine chemicals, and petrochemicals to maximize reaction yield, minimize waste, and improve process efficiency. Optimization is keeping pace with variations in multiple reaction conditions and sustaining a shift from laboratories to industries. Herein, we report an integrated continuous flow reactor platform with Bayesian optimization (BO)-assisted reaction optimization that can autonomously explore the optimal conditions for photochemical bromination reactions of biologically active sartan intermediates. Further, the controlled optimized parameter is extended towards the efficient solar light utility for bromination reactions, and the reaction is achieved in a residence time of 32 sec with an excellent space–time yield of 7 kg L⁻¹ h⁻¹. The individual photobromination and nucleophilic substitution steps for sartan intermediate synthesis smoothly transitioned from the mg h⁻¹ to kg h⁻¹ production. In addition, autonomously explored bromination conditions are integrated with continuous flow tools for synthesizing, extracting, and purifying the angiotensin II receptor blocker intermediate within only 7.2 min.