Pd-catalyzed cross-coupling reactions that form C–N bonds have become useful methods to synthesize anilines and aniline derivatives, an important class of compounds throughout chemical research. A key factor in the widespread adoption of these methods has been the continued development of reliable and versatile catalysts that function under operationally simple, user-friendly conditions. This review provides an overview of Pd-catalyzed N-arylation reactions found in both basic and applied chemical research from 2008 to the present. Selected examples of C–N cross-coupling reactions between nine classes of nitrogen-based coupling partners and (pseudo)aryl halides are described for the synthesis of heterocycles, medicinally relevant compounds, natural products, organic materials, and catalysts.

Applications of Palladium-Catalyzed C–N Cross-Coupling Reactions

Flow chemistry involves the use of channels or tubing to conduct a reaction in a continuous stream rather than in a flask Flow equipment provides chemists with unique control over reaction parameters enhancing reactivity or in some cases enabling new reactions This relatively young technology has received a remarkable amount of attention in the past decade with many reports on what can be done in flow Until recently, however, the question, “Should we do this in flow?” has merely been an afterthought This review introduces readers to the basic principles and fundamentals of flow chemistry and critically discusses recent flow chemistry accounts

The Hitchhiker's Guide to Flow Chemistry

Based on the principles and metrics of green chemistry and sustainable development, biocatalysis is both a green and sustainable technology. This is largely a result of the spectacular advances in molecular biology and biotechnology achieved in the past two decades. Protein engineering has enabled the optimization of existing enzymes and the invention of entirely new biocatalytic reactions that were previously unknown in Nature. It is now eminently feasible to develop enzymatic transformations to fit predefined parameters, resulting in processes that are truly sustainable by design. This approach has successfully been applied, for example, in the industrial synthesis of active pharmaceutical ingredients. In addition to the use of protein engineering, other aspects of biocatalysis engineering, such as substrate, medium, and reactor engineering, can be utilized to improve the efficiency and cost-effectiveness and, hence, the sustainability of biocatalytic reactions. Furthermore, immobilization of an enzyme ...

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Role of Biocatalysis in Sustainable Chemistry

Continuous-flow photochemistry in microreactors receives a lot of attention from researchers in academia and industry as this technology provides reduced reaction times, higher selectivities, straightforward scalability, and the possibility to safely use hazardous intermediates and gaseous reactants. In this review, an up-to-date overview is given of photochemical transformations in continuous-flow reactors, including applications in organic synthesis, material science, and water treatment. In addition, the advantages of continuous-flow photochemistry are pointed out and a thorough comparison with batch processing is presented.

Applications of Continuous-Flow Photochemistry in Organic Synthesis, Material Science, and Water Treatment

The successes and failures of past research in the development of microfluidic reactors for chemical synthesis are highlighted. Current roadblocks are assessed and a series of challenges for the future of this area are identified.

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The past, present and potential for microfluidic reactor technology in chemical synthesis

Ten key issues in modern flow chemistry.

Laboratory scaled flow-through processes have seen an explosive development over the past decade and have become an enabling technology for improving synthetic efficiency through automation and process optimization. Practically, flow devices are a crucial link between bench chemists and process engineers. The present review focuses on two unique aspects of modern flow chemistry where substantial advantages over the corresponding batch processes have become evident. Flow chemistry being one out of several enabling technologies can ideally be combined with other enabling technologies such as energy input. This may be achieved in form of heat to create supercritical conditions. Here, indirect methods such as microwave irradiation and inductive heating have seen widespread applications. Also radiation can efficiently be used to carry out photochemical reactions in a highly practical and scalable manner. A second unique aspect of flow chemistry compared to batch chemistry is associated with the option to carry out multistep synthesis by designing a flow set-up composed of several flow reactors. Besides their role as chemical reactors these can act as elements for purification or solvent switch.

Flow Chemistry – A Key Enabling Technology for (Multistep) Organic Synthesis

Interest in magnetic nanoparticles has increased considerably lately, with diverse applications as magnetic liquids, in catalysis, in biotechnology and biomedicine, and in magnetic resonance spectroscopy. A principal problem associated with naked metallic nanoparticles is their high chemical reactivity, in particular oxidation by air. This drawback can be overcome by coating the nanoparticles with SiO2, metal oxides, gold, or carbon. Several applications of these nanoparticles for quasi-homogeneous catalysis have been disclosed. These particles are typically removed after the reaction by exploiting their magnetic properties. An unexploited and very important feature of magnetic materials is the possibility of heating them in an electromagnetic field. It has been demonstrated that isolated magnetic nanoparticles show magnetic behavior different from that in the bulk. These magnetic nanoparticles when coated with a silica shell can show superparamagnetic behavior. The silica coating prevents the magnetic cores from coupling, thereby preserving their superparamagnetic properties. These composites do not have a residual magnetization and their magnetization curves are anhysteretic. However, the susceptibility of a superparamagnetic material is almost as high as that of a ferromagnetic material. The concept of magnetically induced hyperthermia is based on specific properties of the magnetic nanoparticles upon exposure to a constantly changing magnetic field. Surprisingly, this property of magnetic nanoparticles has so far not been applied in chemical synthesis, although organic chemists are constantly testing new technologies such as microwave irradiation, solid-phase synthesis, and new reactor designs in their work with the goal of performing syntheses and workups more efficiently. Herein we disclose the first application of heating magnetic silica-coated nanoparticles in an electromagnetic field. We demonstrate that these hot particles can be ideally used inside a microfluidic fixed-bed reactor for performing chemical syntheses including catalytic transformations. Thus, besides conventional and microwave heating, magnetic induction in an electromagnetic field is a third way to introduce thermal energy to a reactor. Superparamagnetic materials like nanoparticles 1 can be heated in mediumor high-frequency fields. As the technical setup for the middle-frequency field (25 kHz) is simpler (see Figure 1b,c), we investigated the electromagnetic induction of heat in magnetic nanoparticles in this frequency range. In principal, the processes can be operated in a cyclic or a continuous mode. The inductor can accommodate a flowthrough reactor (glass; 14 cm length, 9 mm internal diameter), which is filled with superparamagnetic material 1. The reactor can be operated up to a backup

Inductive Heating for Organic Synthesis by Using Functionalized Magnetic Nanoparticles Inside Microreactors

Superparamagnetic nanoparticles coated with silica gel or alternatively steel beads are new fixed-bed materials for flow reactors that efficiently heat reaction mixtures in an inductive field under flow conditions. The scope and limitations of these novel heating materials are investigated in comparison with conventional and microwave heating. The results suggest that inductive heating can be compared to microwave heating with respect to rate acceleration. It is also demonstrated that a very large diversity of different reactions can be performed under flow conditions by using inductively heated flow reactors. These include transfer hydrogenations, heterocyclic condensations, pericyclic reactions, organometallic reactions, multicomponent reactions, reductive cyclizations, homogeneous and heterogeneous transition-metal catalysis. Silica-coated iron oxide nanoparticles are stable under many chemical conditions and the silica shell could be utilized for further functionalization with Pd nanoparticles, rendering catalytically active heatable iron oxide particles.

Sascha Ceylan

Papers

Ten key issues in modern flow chemistry.

Flow Chemistry – A Key Enabling Technology for (Multistep) Organic Synthesis

Inductive Heating for Organic Synthesis by Using Functionalized Magnetic Nanoparticles Inside Microreactors

Inductive Heating with Magnetic Materials inside Flow Reactors

Heating under High‐Frequency Inductive Conditions: Application to the Continuous Synthesis of the Neurolepticum Olanzapine (Zyprexa)