Sebastián Pinzón-López, Dominik Ebert, Emelie E. Reuber, Matthias Kraume, Peter H. Seeberger and José Danglad-Flores*,
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Bulk Mixing in a Milligram-Scale Solid Phase Batch Reactor
Adequate mixing is essential during reactions, especially in heterogeneous systems such as Solid Phase Synthesis (SPS), where the reagents transit from the fluid phase into the solid support. Despite the importance of mixing, a quantitative analysis within a theoretical framework is missing for SPS reactors. We analyze mechanical stirring (100–1300 rpm) and argon bubbling (1–30 cm3/min; 0.02–0.70 cm/s) as mixing methods in a milligram-scale batch reactor. Digital Image Analysis (DIA) was used to characterize the liquid mixing and particle dispersion. Typical solvents for SPS of biomolecules─acetonitrile (ACN), dichloromethane (DCM), and dimethylformamide (DMF)─were studied. The dispersion model represented the mixing process. Both mixing methods homogenize the liquid in times as short as 1s. Particle dispersion is accomplished in DCM and DMF but is limited in ACN, where the Archimedes number (Ar) was larger. The synthesis of various glycan probes through Automated Glycan Assembly (AGA) suggests that adequate mixing and thermal conditions are indispensable for process optimization.
期刊介绍：
The journal Organic Process Research & Development serves as a communication tool between industrial chemists and chemists working in universities and research institutes. As such, it reports original work from the broad field of industrial process chemistry but also presents academic results that are relevant, or potentially relevant, to industrial applications. Process chemistry is the science that enables the safe, environmentally benign and ultimately economical manufacturing of organic compounds that are required in larger amounts to help address the needs of society. Consequently, the Journal encompasses every aspect of organic chemistry, including all aspects of catalysis, synthetic methodology development and synthetic strategy exploration, but also includes aspects from analytical and solid-state chemistry and chemical engineering, such as work-up tools，process safety, or flow-chemistry. The goal of development and optimization of chemical reactions and processes is their transfer to a larger scale; original work describing such studies and the actual implementation on scale is highly relevant to the journal. However, studies on new developments from either industry, research institutes or academia that have not yet been demonstrated on scale, but where an industrial utility can be expected and where the study has addressed important prerequisites for a scale-up and has given confidence into the reliability and practicality of the chemistry, also serve the mission of OPR&D as a communication tool between the different contributors to the field.
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