Microreactors in Organic Chemistry and Catalysis, Second Edition (2013)
Preface to the First Edition
Microreactor technology is no longer in its infancy and its applications in many areas of science are emerging. This technology offers advantages to classical approaches by allowing miniaturization of structural features up to the micrometer regime. This book compiles the state of the art in organic synthesis and catalysis performed with microreactor technology. The term “microreactor” has been used in various contexts to describe different equipment, and some examples in this book might not justify this term at all. But most of the reactions and transformations highlighted in this book strongly benefit from the physical properties of microreactors, such as enhanced mass and heat transfer, because of a very large surface-to-volume ratio as well as regular flow profiles leading to improved yields with increased selectivities. Strict control over thermal or concentration gradients within the microreactor allows new methods to provide efficient chemical transformations with high space–time yields. The mixing of substrates and reagents can be performed under highly controlled conditions leading to improved protocols. The generation of hazardous intermediates in situ is safe as only small amounts are generated and directly react in a closed system. First reports that show the integration of appropriate analytical devices on the microreactor have appeared, which allow a rapid feedback for optimization.
Therefore, the current needs of organic chemistry can be addressed much more efficiently by providing new protocols for rapid reactions and, hence, fast access to novel compounds. Microreactor technology seems to provide an additional platform for efficient organic synthesis – but not all reactions benefit from this technology. Established chemistry in traditional flasks and vessels has other advantages, and most reactions involving solids are generally difficult to be handled in microreactors, though even the synthesis of solids has been described using microstructured devices.
In the first two chapters, the fabrication of microreactors useful for chemical synthesis is described and opportunities as well as problems arising from the manufacture process for chemical synthesis are highlighted. Chapter 1 deals with the fabrication of metal- and ceramic-based microdevices, and Brandner describes different techniques for their fabrication. In Chapter 2, Frank highlights the microreactors made from glass and silicon. These materials are more known to the organic chemists and have therefore been employed frequently in different laboratories. In Chapter 3, Barrow summarizes the use and properties of microreactors and also takes a wider view of what microreactors are and what their current and future uses can be.
The remaining chapters in this book deal with different aspects of organic synthesis and catalysis using the microreactor technology. A large number of homogeneous reactions performed in microreactors have been sorted and structured by Ryu et al. in Chapter 4.1, starting with very traditional, acid- and base-promoted reactions. They are followed by metal-catalyzed processes and photochemical transformations, which seem to be particularly well suited for microreactor applications. Heterogeneous reactions and the advantage of consecutive processes using reagents and catalysts on solid support are compiled by Ley et al. in Chapter 4.2. Flow chemistry is especially advantageous for such reactions, but certain limitations to supported reagents and catalysts still exist. Recent advances in stereoselective transformations and in multistep syntheses are explained in detail. Other biphasic reactions are dealt with in the following two chapters. In Chapter 4.3, we focus on liquid–liquid biphasic reactions and focus on the advantages that microreactors can offer for intense mixing of immiscible liquids. Organic reactions performed under liquid–liquid biphasic reaction conditions can be accelerated in microreactors, which is demonstrated using selected examples. The larger area of gas–liquid biphasic reactions is dealt with by Hessel et al. in Chapter 4.4. After introducing different contacting principles under continuous flow conditions, various examples show clearly the prospects of employing microreactors for such reactions. Aggressive and dangerous gases such as elemental fluorine can be handled and reacted safely in microreactors. The emergence of the bioorganic reactions is described by vanHest et al. in Chapter 4.5. Several of the reactions explained in this chapter are targeted toward diagnostic applications. Although on-chip analysis of biologic material is an important area, the results of initial research showing biocatalysis can also now be used efficiently in microreactors are summarized in this chapter. In Chapter 5, Hessel et al.explain that microreactor technology is already being used in the industry for the continuous production of chemicals on various scales. Although only few achievements have been published by industry, the insights of the authors into this area allowed a very good overview on current developments. Owing to the relatively easy numbering up of microreactor devices, the process development can be performed at the laboratory scale without major changes for larger production. Impressive examples of current production processes are given, and a rapid development in this area is expected over the next years. I am very grateful to all authors for their contributions and I hope that this compilation of organic chemistry and catalysis in microreactors will lead to new ideas and research efforts in this field.
Preface to the Second Edition
The continued and increased research efforts in microreactor and flow chemistry have led to an impressive increase in publications in recent years and even to a translation of the first edition of this book into Chinese. This is reflected not only in an update and expansion of all chapters of the first edition but also in the addition of several new chapters to this second edition.
In the first three chapters, Barrow, Brandner, and Frank, respectively, describe properties and fabrication methods of microreactors. In Chapter 4, Moore and Jensen give detailed insights into current methods of online and offline analyses, the potential of rapid optimization of reactions using flow technology, and the combination of analysis and optimization. For better readability, the material on organic synthesis has been split into five different chapters. Ryu et al. have extended their chapter on homogeneous reactions in microreactors, while Watts and Wiles have elaborated the topics of photochemistry, electrochemistry, and radiopharmaceutical synthesis in a new chapter as reactions in these areas are very suitable for being carried out using flow chemistry devices and many publications have recently appeared.
Takasu has written a comprehensive chapter on heterogeneous reactions in microreactors and a many different reactions can be found in this part. We have updated our chapter on liquid–liquid biphasic reactions and Hessel et al. have provided an update on the gas–liquid biphasic reactions. The chapter on bioorganic and biocatalytic reactions by Miyazaki et al. is a comprehensive overview of the developments in this area and highlights the advantages that flow chemistry can offer for research in bioorganic chemistry.
The final chapter by Hessel et al. on industrial microreactor process development up to production has seen a dramatic increase as in many areas industry is now adopting flow chemistry with all its advantages for research and for small- to medium-scale production.
I am again very grateful to all authors for providing updates or completely new contributions and I hope that this compilation of chemistry and catalysis in microreactors will stimulate new ideas and research efforts.