Olefin Autoxidation in Flow

Handling hazardous multiphase reactions in flow brings not only safety advantages but also significantly improved performance, due to better mass transfer characteristics. In this paper, we present a continuous microreactor setup, capable of performing olefin autoxidations with O₂, under solvent-free and catalyst-free conditions. Owing to the transparent reactor design, consumption of O₂ can be visually followed and exhaustion of the gas bubbles marks a clear end point along the channel length coordinate. Tracking the position of this end point enables measuring effective rate constants. The developed system was calibrated using the well-studied β-pinene substrate, and was subsequently applied to the synthetically interesting transformation of (+)-valencene to (+)-nootkatone. For the latter, a space-time yield was obtained that is at least 3 orders of magnitude larger than that realized with established biotechnology approaches

Mass Transport and Reactions in the Tube-in-Tube Reactor

The tube-in-tube reactor is a convenient method for implementing gas/liquid reactions on the microscale, in which pressurized gas permeates through a Teflon AF-2400 membrane and reacts with substrates in liquid phase. Here we present the first quantitative models for analytically and numerically computing gas and substrate concentration profiles within the tube-in-tube reactor. The model accurately predicts mass transfer performance in good agreement with experimental measurement. The scaling behavior and reaction limitations of the tube-in-tube reactor are predicted by modeling and compared with gas/liquid micro- and minireactors. The presented model yields new insights into the scalability and applicability of the tube-in-tube reactor

Microfluidic Continuous Seeded Crystallization: Extraction of Growth Kinetics and Impact of Impurity on Morphology

We describe a continuous microfluidic system for seeded crystallization of small organic molecules, such as active pharmaceuticals, and demonstrate integration with in situ detection tools for determining the size and polymorphic form of the crystals. This integrated device is used to extract growth kinetics, as a screening platform for process parameter effects and optimization, and to gain insight into the fundamentals of the crystallization process. In addition, the microfluidic system also allows studies of additive effects on the crystal habit. The method is demonstrated with growth kinetics for α-, β-, and γ-forms of glycine along with the effects upon the morphology of adding glutamic acid and methionine

A pH-Sensitive Laser-Induced Fluorescence Technique To Monitor Mass Transfer in Multiphase Flows in Microfluidic Devices

We present a pH-sensitive laser-induced fluorescence (LIF) technique to investigate mass transfer in reactive flows. As a fluorescent dye, we used 5-(and-6)-carboxy SNARF-1, which, when excited with a pulsed Nd:YAG laser at 532 nm, provides good sensitivity in the range 4 ≤ pH ≤ 12. For validation, we first applied the dye to single-phase reactive flows by investigating the neutralization of sodium hydroxide with hydrochloric acid. Comparison to the classical passive mixing case showed that this dye was able to capture the reaction progress and to quantify the mass transport. Next, we investigated the absorption of CO₂ in an alkaline solution using gas–liquid flow and found that the LIF technique is able to quantify the local mass-transfer rate in microfluidic systems. Results for different microchannel geometries highlight the strong connection between local mass transfer and secondary flow structures in gas–liquid Taylor flow

An Automated Continuous-Flow Platform for the Estimation of Multistep Reaction Kinetics

Automated continuous flow systems coupled with online analysis and feedback have been previously demonstrated to model and optimize chemical syntheses with little <i>a priori</i> reaction information. However, these methods have yet to address the challenge of modeling and optimizing for product yield or selectivity in a multistep reaction network, where low selectivity toward desired product formation can be encountered. Here we demonstrate an automated system capable of rapidly estimating accurate kinetic parameters for a given reaction network using maximum likelihood estimation and a <i>D</i>-optimal design of experiments. The network studied is the series–parallel nucleophilic aromatic substitution of morpholine onto 2,4-dichloropyrimidine. To improve the precision of the estimated parameters, we demonstrate the use of the automated platform first in optimization of the yield of the less kinetically favorable 2-substituted product. Then, upon isolation of the intermediates, we use the automated system with maximum <i>a posteriori</i> estimation to minimize uncertainties in the network parameters. From considering the steps of the reaction network in isolation, the kinetic parameter uncertainties are reduced by 50%, with less than 5 g of the dichloropyrimidine substrate consumed over all experiments. We conclude that isolating pathways in the multistep reaction network is important to minimizing uncertainty for low sensitivity rate parameters

A Clock Reaction Based on Molybdenum Blue

Clock reactions are rare kinetic phenomena, so far limited mostly to systems with ionic oxoacids and oxoanions in water. We report a new clock reaction in cyclohexanol that forms molybdenum blue from a noncharged, yellow molybdenum complex as precursor, in the presence of hydrogen peroxide. Interestingly, the concomitant color change is reversible, enabling multiple clock cycles to be executed consecutively. The kinetics of the clock reaction were experimentally characterized, and by adding insights from quantum chemical calculations, a plausible reaction mechanism was postulated. Key elementary reaction steps comprise sigmatropic rearrangements with five-membered or bicyclo[3.1.0] transition states. Importantly, numerical kinetic modeling demonstrated the mechanism’s ability to reproduce the experimental findings. It also revealed that clock behavior is intimately connected to the sudden exhaustion of hydrogen peroxide. Due to the stoichiometric coproduction of ketone, the reaction bears potential for application in alcohol oxidation catalysis

Facile Soft-Templated Synthesis of High-Surface Area and Highly Porous Carbon Nitrides

Mesoporous carbon nitride is synthesized in a one-pot approach using different nonionic surfactants (Pluronic F-127, Pluronic P-123, and Triton X-100) and a melamine cyanurate hydrogen-bonded complex using just water as the solvent. We obtain three-dimensional assembled nanostructures from low-dimensional carbon nitride sheets by taking advantage of supramolecular assembly of melamine and cyanuric acid, moderate interactions between the surfactant and precursors, structure directing effects of the surfactants, and the good thermal stability of the melamine cyanurate sheets formed around the micelles. Different morphologies, including sheetlike, hollow spherical, and tubular or highly porous networks, result depending upon the synthesis approach and the surfactant/precursor ratio. Pseudoternary phase diagrams map the composition of the starting solution to the resultant carbon nitride morphology. Increasing the amount of surfactant leads to a higher carbon residue (C/N ∼ 1) and large BET surface areas (≤300 m²/g). Further tuning of the synthesis parameters as well as addition of HCl produces uniformly porous nanostructures with a high porosity (up to 0.8 cm³/g), a high surface area (>200 m²/g), and yet a stoichiometric C/N ratio (∼0.75). The synthesized high-surface area carbon nitrides show improved light absorption and enhanced photocatalytic activity in a rhodamine B dye degradation reaction under visible light irradiation compared to those of bulk melamine-derived carbon nitride

Characterization and Modeling of the Operating Curves of Membrane Microseparators

The membrane microseparator is a milliliter-scale flow chemistry module that continuously separates a biphasic flow through a PTFE microporous membrane. It has found a wide range of applications in the continuous manufacturing of active pharmaceutical ingredients and fine chemicals, especially those involving multiple synthetic steps. Yet, the accurate prediction and control of the pressure balance needed for successful phase separations is technically challenging. In this article, we present systematic modeling of the operating ranges of the membrane microseparator. We characterize the retention and breakthrough phenomena of the device and develop two new analytic models for retention and breakthrough by taking into consideration the tortuosity factor and pore size distribution. The new models are shown to be better predictors of the experimental results than the original theoretical models based on the simple Young–Laplace equation and the straight-channel Hagen–Poiseuille equation

Multiphase Oscillatory Flow Strategy for <i>in Situ</i> Measurement and Screening of Partition Coefficients

Taking advantage of the difference between the surface energies of aqueous and organic solvents on a Teflon substrate, a fully automated small-scale strategy is developed on the basis of gas-driven oscillatory motion of a biphasic slug for high-throughput <i>in situ</i> measurement and screening of partition coefficients of organic substances between aqueous and organic phases. The developed oscillatory flow strategy enables single partition coefficient data point measurement within 8 min (including the sample preparation time) which is 360 times faster than the conventional “shake-flask” method, while using less than a 30 μL volume of the two phases and 9 nmol of the target organic substance. The developed multiphase strategy is validated using a conventional shake-flask technique. Finally, the developed strategy is extended to include automated screening of partition coefficients at physiological temperature

High Throughput Synthesis of Uniform Biocompatible Polymer Beads with High Quantum Dot Loading Using Microfluidic Jet-Mode Breakup

Uniform polymer microbeads with highly loaded quantum dots (QDs) are produced using high-throughput coherent jet breakup of a biocompatible poly­(ethylene glycol) diacrylate (PEGDA) prepolymer resin, followed by in-line photopolymerization. A spiraling and gradually widening channel enables maximum absorption of radiated UV light for the in-line photopolymerization without coalescence and clogging issues. Although the dripping mode in general provides superior uniformity to the jet mode, our nozzle design with tapered geometry brings controlled jet breakup leading to 3% of uniform particle size distribution, comparable to dripping-mode performance. We achieve a maximum production rate of 2.32 kHz, 38 times faster than the dripping mode, at a same polymer flow rate. In addition, the jet-mode scheme provides better versatility with 3 times wider range of size control as well as the compatibility with viscous fluids that could cause pressure buildup in the microsystem. As a demonstration, a QD-doped prepolymer resin is introduced to create uniform biocompatible polymer beads with 10 wt % CdSe/ZnSe QD loading. In spite of this high loading, the resulting polymer beads exhibits narrow bandwidth of 28 nm to be used for the ultrasensitive bioimaging, optical coding, and sensing sufficiently with single bead