Multi-Scale Reaction Modelling: A Route to a Sustainable Future?

化学和制药行业向更环保和更可持续的制造方法的转变正在导致更多地实施流程。这些流程允许更灵活和连续地生产更多样化的化学靶标。新型流动反应器的发展使光化学和电化学更容易获得，为复杂的化学合成提供了更多的能量和原子效率途径。模块化流动系统允许更安全地使用危险化学品和更恶劣的条件，因此大大扩展了过程窗口。当与PAT相结合进行持续监测时，就有很大的机会实现反应自动化和自我优化。当与计算建模相结合时，这种连续监测将允许更有效地利用所获取的数据，从而快速实现最佳操作条件。制造公司越来越多地使用创建化学系统的计算模型来预测其过程是如何运作的。以前，建模主要用于工业规模，然而，由于向较小规模过程的转变，有必要了解千克和实验室规模上反应器的特性。像gPROMS这样的建模程序是专门用来模拟化学生产过程的。虽然gPROMS对整个过程给出了很好的预测，但它对小型实验室反应堆的预测有限。计算流体动力学（CFD）已广泛应用于航空航天和汽车工业中，以实现流体流动的可视化，最近它也被应用于制造过程中对反应器内流动的可视化。了解反应器内的流体流动，结合反应动力学，对于估计生产过程规模化所需的变化是必不可少的。这种扩大规模的预测和快速建立最佳工艺参数的能力将通过确保试剂和能源的最小浪费，极大地提高可持续性和效率。该项目的目标是为特定的化学产品创建量身定制的模型，以促进流动反应系统的扩大。这将使用CFD来优化反应堆设计，使用gPROMS来优化操作条件。这两种方法的结合将允许从实验室到工业规模的多步骤过程的快速和容易的优化。起点将是诺丁汉大学最近开发的电涡旋反应堆的放大，该反应堆使用一个旋转的圆柱体在一个静态的外圆柱体内，在两个圆柱体之间的间隙内产生泰勒-库埃特漩涡。该反应器已成功地用于n -甲酰吡咯烷每天多摩尔的甲氧基化反应。第一步是将产量从每天0.5公斤增加到每天20公斤左右。这将通过CFD建模来解决，以适应这种大规模生产的反应器设计，特别是研究将产生的大量氢气的影响。在建立反应器优化设计后，将利用gPROMS建立涉及电涡的伸缩反应器系统的最优运行条件。然后，这可以扩展到优化其他漩涡反应器设计的化合物特定反应。

A shift towards greener and more sustainable manufacturing methods by chemical and pharmaceutical industries is leading to increased implementation of flow processes. These flow processes allow for more flexible and continuous production of a more diverse range of chemical targets. The development of new flow reactors has allowed photo- and electrochemistry to be more widely accessible, allowing for more energy and atom efficient routes for complex chemical syntheses. Modular flow systems allow for the safer use of hazardous chemicals and harsher conditions so greatly expand the process window. When combined with PAT for continuous monitoring there is great opportunity for reaction automation and self-optimisation. When combined with computational modelling, this continuous monitoring will allow for more effective use of the acquired data leading to rapid realization of optimal operating conditions. Creating computational models of chemical systems is increasingly being used by manufacturing companies to make predictions on how their process is operating. Previously, modelling has mainly been used on an industrial scale, however, due to the shift towards smaller scale processes it is necessary to understand the characteristics of reactors on the kilo- and lab scales. Modelling programmes such as gPROMS are purpose built to model chemical production processes. Whilst gPROMS gives good predictions on full processes it has limited predictions down to small scale laboratory reactors. Computational Fluid Dynamics (CFD) has widely been used in the aerospace and automotive industries to visualise fluid flow, recently this has also been applied to manufacturing processes visualising flow within reactors. Understanding the fluid flow within reactors, combined with reaction kinetics, is essential for estimating changes required in the scale up of production processes. The prediction of this scale-up and the ability to quickly establish the optimal process parameters will vastly improve the sustainability and efficiency by ensuring minimal waste in both reagents and energy. The goal of this project is to create tailored models to specific chemical products to facilitate the scale-up of flow reaction systems. This will be done using CFD to optimise reactor design and gPROMS to optimise for operating conditions. The combination of these two methods will allow for quick and easy optimisation of multi-step processes from laboratory to industrial scale. The starting point will be the scale-up of the electro-vortex reactor recently developed at Nottingham, which uses a rotating cylinder inside a static outer cylinder to create Taylor-Couette vortices within the gap between the two cylinders. These vortices de-couple the mixing of reactants from residence time and the reactor has been successfully used for multi-mole per day methoxylation of N-formylpyrrolidine. The first step is to scale-up the production of this from 0.5kg/day to around 20kg/day. This will be tackled by CFD modelling to adapt the reactor design for this larger scale production particularly to investigate the effects of the large volumes of H2 that will be generated. After establishing the optimal reactor design, gPROMS will be used to establish optimal operating conditions within telescoped reactor systems involving the electro-vortex. This can then be expanded to optimising other vortex reactor designs for compound specific reactions.