Major efforts in the research field of microwave assisted organic synthesis have demonstrated the specific benefits associated with the use of microwave irradiation such as selective and rapid heating of the reaction mixture. In many case studies, these benefits eventually lead to a significant enhancement in the production rates. Therefore, microwave assisted flow synthesis can be an interesting alternative for fine chemical production in conventionally heated batch reactors. However, realization of microwave assisted flow synthesis at kilogram scale requires a proper design of tubular reactors integrated with the microwave heating source, i.e. the cavity. The design of these reactors should primarily be able to overcome the limitations by the penetration depth of the microwaves, i.e. ¿0.013 m. Moreover, operation based on microwave heating should allow accurate temperature control by precise tuning and quantification of the microwave energy distribution. Therefore, being case specific, design efforts are necessary for the microwave setup as well as for the reactor configuration. Heating in monomode microwave equipment is energy efficient and fast in comparison to heating in multimode microwave equipment. State-of-the-art microwave cavities, however, lack in providing important functionalities, such as a predictable electric field pattern, tuning facility, detailed energy distribution and possibilities for modular scale-up. A waveguide type monomode microwave cavity in combination with the short circuit, stub tuners, and isolators can provide the aforementioned functionalities for continuously operated reactors. This type of microwave setup allows an accurate elaboration of energy balances for efficient and uniform heating. Additionally the use of multiple cavities connected to a single microwave generator via a main waveguide permits modular scale-up. The dielectric properties (i.e. dielectric constant and dielectric loss) of a microwave absorbing load (e.g. reaction mixture/solvent) are significantly dependent on temperature. As a consequence, microwave absorption, which involves interaction of the electromagnetic field with the applied load, is a recurring process. Therefore, detailed understanding of the dielectric property change with temperature is a prerequisite for a proper design of the load to be used under stop-flow (batch) and continuous-flow conditions. For stop-flow conditions, the highest heating efficiency (70 %) is observed for a load diameter equal to and larger than half of the wavelength of the microwaves in the liquid medium. For continuous-flow conditions, the heating efficiency increases linearly with the load diameter. However, microwave leakage above the propagation diameter (i.e. half wavelength) limits further increase of the load diameter in continuous operation. The high energy intensity of the focused electromagnetic field in case of waveguide type microwave cavities makes an efficient and controlled continuous operation difficult, especially when a strong microwave absorbing load (e.g. ethanol) is present. In cases, such as the reaction of ethanol and acetic acid to produce ethyl acetate over a strong acid ion-exchange resin, a milli reactor-heat exchanger combination with a co-current flow of a microwave transparent solvent (coolant) can be a solution. Here, rapid volumetric heating to the reaction temperature can be achieved by microwaves before the reaction mixture enters into the catalyst bed. Additionally, the coolant not only limits overheating of the reaction mixture but also permits heat integration, resulting in extended reactor lengths and efficient heating (i.e. 96 %). However, stagnancy in the flow of the microwave absorbing load results in a poor convective heat transport. As a consequence, stagnant layer formation caused either by any insertion (of system components, such as fiber optic sensors) or at the reactor walls, yields higher temperatures and lower microwave energy dissipation regions. One of the promising approaches for scaling microwave assisted flow synthesis is numbering up. The numbering up approach is based on parallelization of tubular structured reactors with a channel diameter in the millimeter range. The performance of such a configuration is evaluated by a multi-tubular milli-reactor/heat exchanger system with a thin Cu film on the inner walls of the reactor tubes. The thin Cu film provides uniform microwave absorption and it improves the production rate by acting as a heated catalytically active surface, as demonstrated in the synthesis of 1,3-diphenyl-2-propynyl-piperidine from benzaldehyde, piperidine, and phenylacetylene. Controlled selective heating of the thin Cu film is achievable by using a counter-current flow of a microwave transparent coolant (toluene). The coolant flow avoids Cu burning and reduces leaching, consequently improving the steady state catalytic performance of the Cu coated reactor tubes. Higher temperatures, i.e. at least 100 K higher than the bulk liquid, are achievable at the locus of the reaction, i.e. the catalyst surface, purely due to selective microwave heating. Another approach to realize higher production rates is utilization of multiple microwave cavities in series. In this approach, the process stream is taken from one cavity to the next where the process efficiency is well optimized over each consecutive cavity. Transient operation through each optimized cavity and utilization of multiple cavities in series increases conversion and consequently results in higher production rate. Additionally, known kinetics allows estimation of the production rate for each additional cavity in the series. This approach of scale-up is possible at minimized grid to applicator losses by connecting multiple cavities to a single microwave generator via a main waveguide. Scale-up approaches based on parallelization of tubular structured reactors as well as on utilization of multiple microwave cavities in series were found to be successful. Application of microwaves as a process intensification tool, especially in the case of organic synthesis, is very attractive for liquid-solid reactions, where the solid is the selectively (microwave) heated catalyst
