Bulk Mixing in a Milligram-Scale Solid Phase Batch Reactor

IF 3.5 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2025-09-01 DOI:10.1021/acs.oprd.5c00194

Sebastián Pinzón-López, Dominik Ebert, Emelie E. Reuber, Matthias Kraume, Peter H. Seeberger and José Danglad-Flores*,

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引用次数: 0

Abstract

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.

Abstract Image

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在毫克级固相间歇式反应器中进行散装混合

在反应过程中，充分的混合是必不可少的，特别是在非均相系统中，如固相合成（SPS），其中试剂从流体相过渡到固体载体。尽管混合的重要性，在理论框架内的定量分析SPS反应器是缺失的。在mg级间歇式反应器中，对机械搅拌（100-1300 rpm）和氩气鼓泡（1-30 cm3/min; 0.02-0.70 cm/s）两种混合方法进行了分析。采用数字图像分析（DIA）对液体混合和颗粒分散进行了表征。研究了生物分子SPS的典型溶剂——乙腈（ACN）、二氯甲烷（DCM）和二甲基甲酰胺（DMF）。分散模型代表混合过程。两种混合方法都能在短至15秒的时间内使液体均匀化。粒子分散在DCM和DMF中完成，但在ACN中受到限制，其中阿基米德数（Ar）较大。通过自动聚糖组装（AGA）合成各种聚糖探针表明，适当的混合和热条件是优化工艺的必要条件。

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来源期刊

Organic Process Research & Development 化学-应用化学

CiteScore

6.90

自引率

14.70%

发文量

251

审稿时长

2 months

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.