Can Ultrasound Replace Seeding in Flow Reactive Crystallization of an Aromatic Amine?

IF 3.1 3区 化学 Q2 CHEMISTRY, APPLIED
Biyu Zhang, Georgios D. Stefanidis and Tom Van Gerven*, 
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引用次数: 0

Abstract

Continuous crystallization has gained substantial interest due to its high product reproducibility, high labor efficiency, and low capital and production costs. Continuous seeding is preferable and often even required in the application of pharmaceuticals, which presents a bottleneck in continuous crystallization. This work proposes to apply ultrasound for continuous in situ seeding in the continuous reactive crystallization of an aromatic amine. Flow crystallization experiments with both ultrasound and conventionally prepared seeds were conducted. It was found that sonication initiated nucleation and continuously produced crystals in a stable manner. The nucleation rate could be controlled by adjusting the sonication power, highlighting the advantages of the sonicated seed generation strategy. Experiments under different flow conditions demonstrated that a higher flow rate combined with an appropriate sonication power was favorable for robust particle quality, reduced likelihood of clogging, and better reproducibility. Compared with the conventional addition of seed crystals, sonication-induced crystallization achieved higher yields and produced products with a narrow and unimodal size distribution. All sonicated experiments exhibited high robustness, indicating the feasibility and reliability of this method as a replacement for conventional seeding techniques in the continuous reactive crystallization of the studied compound. In summary, using ultrasound for continuous in situ seeding of the aromatic amine offers unique advantages in process robustness and product quality control, providing a promising strategy for continuous crystallization of similar systems.

超声能代替芳香胺流动反应结晶中的播种吗?
连续结晶因其产品可重复性高、劳动效率高、资金和生产成本低而受到广泛关注。在药物的应用中,连续播种是优选的,甚至经常需要,这是连续结晶的瓶颈。这项工作提出了应用超声连续原位播种在连续反应结晶芳胺。用超声和常规制备的种子进行了流动结晶实验。结果表明,超声触发成核并稳定地连续生成晶体。通过调节超声功率可以控制成核速率,突出了超声制种策略的优势。不同流量条件下的实验表明,较高的流量和适当的超声功率相结合,有利于提高颗粒质量,减少堵塞的可能性,并具有更好的再现性。与传统的种子晶体添加相比,超声诱导结晶的产率更高,产物尺寸分布窄且单峰。所有的超声实验都显示出较高的稳健性,表明该方法在所研究化合物的连续反应结晶中替代传统的播种技术是可行和可靠的。综上所述,利用超声波进行芳香胺的连续原位播种在工艺稳健性和产品质量控制方面具有独特的优势,为类似系统的连续结晶提供了一种有前途的策略。
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来源期刊
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.
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