Microreactor technology continuous processes

Hence there is considerable potential for these slow reactions to be intensified. Microreactor technology/continuous processes can here also play a critical role in process development. It allows reactions to be conducted almost solvent free [16] and it permits the boiling point of a mixture to be easily extended by applying pressure [17]. In addition, the combination with other technologies such as microwave techniques is an avenue for further synergies [18]. 

Acke DRJ, Stevens CV, Roman BI (2008) Microreactor technology continuous synthesis of lH-isochromeno[3, 4-d]imidazol-5-ones. Org Process Res Dev 12(5) 921-928... 

Roberge DM, Zimmermann B, Rainone F et al (2008) Microreactor technology and continuous processes in the fine chemical and pharmaceutical industry is the revolution underway Org Process Res Dev 12(5) 905-910 www.syrris.com/. Accessed 14 Sept 2009... 

Figure 5.13 A schematic representation with typical process steps in the fine chemical and pharmaceutical industries and recommendation when to use microreactor technology or continuous processes based on a multipurpose approach (by courtesy of PharmaChem/B5Srl) [44].

The use of microreactor technology for polymer chemistry presents an interesting alternative to conventional processing methods, in both batch and macroscale continuous flow. Microreactors offer a better process control of many exothermic polymerization processes, leading to increased product quality such as narrower polydispersity, and they allow for the synthesis of novel polymeric materials for a range of new applications. 

Continuous microreactor systems have gained a lot of interest in the field of organic synthesis as these possess enhanced mass and heat transfer properties. Microreactor technology also offers a contemporary way of conducting chemical reactions In a more sustainable fashion due to the miniaturization and increased safety, and also In a technically improved manner due to intensified process efficiency. Recent developments in this area related to the synthesis of heterocyclic compounds are recorded in this chapter. Also, telescoping, in which several subsequent reaction steps (with or without purification) can be achieved by connecting different reactors to each other, is covered. 

Thus, microreactor technology, by allowing continuous processes, touches at the heart of fine chemical manufacturing processes, namely it reduces the amount of labor required to run a process. It reduces the amount of labor because it reduces the number of unit operations (or procedures) accomplished by workers. Those operations are performed in situ through an automated system and an appropriate microreactor setup (toolbox concept). The relation between continuous operations and labor is well established in other industries such as the petroleum industry, leading to highly automated and efficient processes. 

Second, a study performed by Lonza (Visp, Switzerland), dealing with current benefits and drawbacks of microreaction technology, was presented [5]. The authors depicted the kind of reaction that prevails in the FCPI and classified them in three main classes. Type A, B and C (very fast, rapid and slow reactions, respectively). Thqr reasoned that up to 50% of the reactions performed at Lonza could benefit from continuous processing. For 44% of lhem a microreactor would be the preferred reaction device. However, the handling of solids reduces the number of reaction candidates to less than 20%. The authors therefore emphasized the development of multi-purpose microreactor modules that can deal with solid phases. Further, Roberge et al. [5] emphasized the potential of MRT to reduce labor costs by highly automated and efficient processes. 

Focus of R D patent increasing interest in continuous microreactor technologies Product improvement Process... 

It is well established that microreactors and continuous flow synthesis enable reactions to be performed more rapidly, efficiently, and selectively than batch reactions. In addition to traditional solution phase synthesis, microreactor technology has now been demonstrated to effldently enable photochemistry and electrochemistry to be more easily introduced into the methodology available to the synthetic chemist. As illustrated within this chapter, it is also possible to conduct PET radiosynthesis within these systems where a key advantage is that the processing time can be substantially reduced. 

However, for commercial production, the use of continuous microreactor technology should be justified by a dear cost advantage in comparison to presenfly applied technologies. The use of microfluidic bioreactors opens up possibilities for new production concepts, particularly continuous processing and flexible scale-up on demand via parallelization. There is, however, a need for a modular networks consisting of upstream steps (reaction) and downstream step (separation and purification), that is, the development of whole biocatalytic processes for real implementation in industrial setting. 

Thus, it is more flexible to run both reactions continuously [64]. A microreactor is used for the more demanding, highly exothermic reaction, whereas a static mixer is sufficient for the second reaction. After laboratory process development, a pilot phase in the so-called continuous small-scale production (c-SSP) comprising microreactor technology followed (see Figure 11.16). The c-SSP plant is a multipurpose and modular approach and can operate from cryogenic to high temperature. 

At Sigma-Aldrich, a pilot study was performed for the transfer of microreactor technology into large-scale production for the synthesis of 2-benzoylpyridine through a Grignard reaction [85]. They transferred the small-scale 2 ml microreactor processes to production in a stainless steel Alfa Laval Art plate reactor and achieved rapid flow rates and continuous production of 200-300 kg of 2-benzoylpyridine per day. 

According to the experts in the field of chemical synthesis, it is more preferable to use continuous process in microreactors for up to 70% of all chemical reactions [19]. Today, a lot of homogeneous reactions in liquid-liquid systems are investigated because they can be simply carried out in microreactors. Heterogeneous reaction systems, both liquid-liquid and gas-liquid, in microreactors are more and more intensively studied and find practical application. Special attention is given to catalytic processes as they dominate in chemical technology. 

The work presented here is based on the development at University of Regensburg by Ulbrich et td. [55]. It utilizes the novel process windows offered by continuous-flow microreactor technology [56]. A conventional industrial batch synthesis of the product 4-hydroxycyclopentanone, which is an important intermediate for pharmaceutical building blocks, was described previously [57]. In a recent publication, Nettekoven et al. [58] described an investigation of a synthetic route for five-membered ring structures used as pharmaceutical synthetic building blocks based on furfuryl alcohol... 

To facilitate the synthesis of hbPG for industrial processing, microreactor technology can be used to obtain polymers with molecular weights up to 1500gmoh In this approach, an efficient continuous process is used, which results in significantly reduced experimental effort, albeit with molecular weight limitations. 

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