Kinetics analysis and automated online screening of aminocarbonylation of aryl halides in flow

Temperature, pressure, gas stoichiometry, and residence time were varied to control the yield and product distribution of the palladium-catalyzed aminocarbonylation of aromatic bromides in both a silicon microreactor and a packed-bed tubular reactor. Automation of the system set points and product sampling enabled facile and repeatable reaction analysis with minimal operator supervision. It was observed that the reaction was divided into two temperature regimes. An automated system was used to screen steady-state conditions for offline analysis by gas chromatography to fit a reaction rate model. Additionally, a transient temperature ramp method utilizing online infrared analysis was used, leading to more rapid determination of the reaction activation energy of the lower temperature regimes. The entire reaction spanning both regimes was modeled in good agreement with the experimental data

Continuous-flow studies of conventionally difficult chemical processes in micro- and mini-reactors

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2010.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student submitted PDF version of thesis.Includes bibliographical references (p. 177-192).Microfluidic systems provide valuable tools for exploring, studying, and optimizing organic syntheses. The small scales and fast transport rates allow for faster experiments and lower amounts of chemicals to be used, reducing costs and increasing safety. Additionally, continuous flow processes allow for a large number of experiments to be performed after a single setup. These advantages were exploited to enable continuous-flow study of chemical syntheses that are hazardous or difficult to perform by conventional methods and of applying the acquired knowledge toward improvement of industrial processes at large scales. Using silicon semiconductor microfabrication techniques, microdevices have designed and produced to address various challenges in continuous-flow reaction study and synthesis, enabling operation at reaction conditions not easily obtained in batch setups or on macroscopic scale. Several model reactions and systems were selected for study and/or augmentation. Silicon micromixers were designed and microfabricated to ensure low-pressure-drop millisecond-scale mixing of liquid streams. The micromixers were used to perform a quantitative kinetics and scale-up study of the direct two-step synthesis of sodium nitrotetrazolate by a Sandmeyer type reaction via a reactive diazonium intermediate. The use of continuous-flow microsystems significantly reduced the typically high explosion hazard associated with the energetic product and intermediate. An epoxide ring opening reaction was augmented and kinetics of the reaction were rapidly obtained using a silicon microreactor at high temperatures and pressures, demonstrating microreactor utility for rapid reaction space profiling, as well as the use of continuous flow to easily study and sample reaction conditions not readily accessible in batch. Scale-up was demonstrated using obtained kinetics. Synthesis steps of two pharmaceutical APIs were thus studied and greatly accelerated, which may be useful for considerations of continuous manufacturing. Finally, a system has been designed and studied to enable microfluidic study of solids forming reactions such as an organic coupling reaction with inorganic salt byproduct precipitate. Conventionally, these solids render such reactions difficult to study in microreactors, which limits the types of chemistries that could be investigated and improved using microfluidic technology. To minimize these constraints, the formation of solids in flow was systematically studied, and a combination of reactor design and application of acoustic forces to effect solid agglomerate disruption was used to allow slurries with relatively large amounts of solids to flow through microchannels.by Nikolay Zaborenko.Ph.D

Kinetic and Scale-up Investigations of Epoxide Aminolysis in Microreactors at High Temperatures and Pressures

A continuous-flow microreactor is applied for a kinetic study of a model β-amino alcohol formation by epoxide aminolysis. A large number of experiments are performed in a short time with minimal reagent consumption. The kinetics of formation of secondary aminolysis between starting epoxide and product are decoupled from the primary synthesis, constructing a complete model for desired product formation. The activation energy for the formation of desired product is observed to be higher than those for regioisomer formation and for secondary aminolysis, indicating that increasing temperature improves selectivity in addition to accelerating the reaction. A set of optimized conditions is then selected for best reaction performance, and a scaled-up process is performed, demonstrating improvement on a meso-scale.Novartis-MIT Center for Continuous Manufacturin

Microfluidic Assisted Synthesis of Hybrid Au–Pd Dumbbell-like Nanostructures: Sequential Addition of Reagents and Ultrasonic Radiation

A sequential-addition microfluidic reactor and an ultrasonic integrated microfluidic reactor were designed to produce with high selectivity hybrid Au–Pd dumbbell-like nanostructures (Au–Pd DBNPs), consisting of a palladium segment tipped with gold heads. A single-stage synthesis was not able to synthesize hybrid nanostructures due to the high reactivity of gold. On the other hand, a two-step method was successful by first synthesizing Pd nanorod-like structures and subsequent growing of Au on the tips of those structures by the localized galvanic replacement reaction. The localized deposition of Au onto both tips of palladium rods was achieved by using two different microfluidic approaches: (i) by sequential injection of gold along the reaction channel at 100 °C and a 5 min residence time, and (ii) by ultrasonic radiation at room temperature and a 2 min residence time. The synthesized Au–Pd DBNPs had higher electrocatalytic activity in the ethanol oxidation reaction in alkaline media than the Pd nanorods