Organic Electrochemistry, Microreactors, and Their Synergy by Jun-ichi Yoshida riven by remarkable improve- equal to length squared. Thus, a feature decreasing yield and selectivity. Solving ments in our understanding of micro spaces is that they have large these issues requires examination of Dof factors governing organic surface-to-volume ratios compared to the reaction conditions, wasting much reactions, the role of organic synthesis macro spaces. Therefore, energy transfer time and manpower. When using has been expanded to various fields of occurs rapidly through an interface in microreactors, however, the production science and technology, such as new micro spaces. volume can be increased by increasing materials and new medicinal agents. Mass transfer.—Another characteristic the operation time and the number of Because of rapid progress in such fields, of microreactors derived from their reactors, if necessary, without changing demands for producing desired organic much greater surface-to-volume ratios is the size of the reactors. Thus, a shift to compounds in a highly efficient and that they make phase boundary reactions industrial production is possible without environmentally benign manner have such as gas/liquid, liquid/liquid or solid/ changing the reaction conditions that been increasing. In order to meet such liquid reactions including electrode were most suitable at the laboratory demands, synergy between organic processes more efficient, because mass scale. Consequently, the usual lag time electrochemistry and microreactors is transfer through or on an interface is between research and development on expected to play a central role. This very fast. the one hand, and industrial production article will provide a brief outline Residence time.—The length of time on the other, can be expected to be of this new fascinating approach. that the solution remains inside the greatly reduced with microreactors. reactor (the residence time) can be Microreactors have been expected Microreactors greatly reduced by adjusting the length to make a revolutionary change in of microchannels and flow speed. This chemical synthesis. For example, highly Microtechnology is no longer feature of microreactors is extremely exothermic, extremely fast reactions are merely the province of computers and useful in controlling short-lived reactive usually carried out by slowly adding one the rest of the electronics field, but species, which can be transferred to of the reaction components to the other. is now moving into many different another location to be used in the The rate of the reaction is determined by areas of science and technology such next reaction before they decompose. the rate of the addition. These types of as mechanics, optics, and fluids. These Therefore, chemical conversions that are reactions can be conducted at a natural days downsizing has been also occurring impossible in macroreactors should be rate using microreactors. Fast reactions in the chemistry. The advantage of made possible by using microreactors. may also cause selectivity problems; downsizing is that it provides better Integration.—Integrated microflow kinetically based selectivity is not efficiencies while also answering reactor systems can be easily constructed obtained because the reaction proceeds society’s demands for conservation of enabling multi-step synthesis using before homogeneity of the solution has resources and energy. The micro device highly unstable reactive intermediates been achieved by mixing. In such cases, used for conducting chemical reactions (Fig. 1). the reactions need to be slowed down by is called a microreactor.1,2 A microreactor Scaling up.—Scaling-up of chemical decreasing the temperature, decreasing is a reactor with microchannels on the reactions from the laboratory flask scale concentrations, or adding additives. micrometer scale. Microreactors are to the industrial production scale suffers However, the use of microreactors not necessarily used solely to produce from a variety of problems such as enables conducting such reactions small amounts of chemical substances. Although the reactor’s capacity at any one time is small, total production capacity over time is much greater than may be imagined because microreactors are normally set up as flow-type reactors with a continuous flow of solution through the reaction chamber. In fact, there are microreactors, though they fit in the palm of the hand, that can produce several tons of a product per year. The characteristics of microreactors can influence the very essence of chemical reactions in the following ways. Mixing.—Most chemical reactions are conducted by combining two substances. The major part of mixing occurs due to molecular diffusion. Time needed for molecular diffusion is proportional to the square of the length of the diffusion path. Therefore, the marked shortening of the diffusion path in a microreactor results in a mixing speed unobtainable in a macro reactor. Energy transfer.—In general, when length is shortened, surface-to-volume ratio increases, because volume is equal FIG. 1. An integrated microflow reactor system consisting of four micromixers and four microtube to length cubed while surface area is reactors. 40 The Electrochemical Society Interface • Summer 2009 without slowing down and production organic synthesis. A number of such Reaction conditions.—Electrochemical with kinetically based selectivity. synthetic transformations have been reactions for organic synthesis have Another important point is the control discovered and developed using organic been usually carried out at or near room of highly reactive, short-lived reactive electrochemistry as “greener” procedures temperature. However, recent progress intermediates. Chemical conversions so far. In addition to conventional in electrochemical reactors enables us that are difficult to achieve using protocols, various new strategies in to perform electrochemical reactions conventional marobatch reactors should organic electrochemistry have been under high-temperature and/or high- become possible using microreactors. developed as follows.3 pressure conditions. Such technology Intramolecular control.—Methods using led to the use of supercritical fluids as Organic Electrochemistry functional groups that control the reaction media. It is also noteworthy reactivity of substrate molecules and that electrolysis can be conducted at Organic electrochemistry provides a reaction pathways are often used in very low temperatures, enabling us straightforward, efficient, and tunable organic synthesis. A method for such to generate and accumulate unstable method for generating a wide variety of intramolecular control has also been reactive species such as organic cations reactive intermediates that are useful in developed in organic electrochemistry; (cation pool method) (Fig. 2). The use of organic synthesis. In fact, radical cations the introduction of a functional group ultrasound in electrochemical synthesis and radical anions can be generated that promotes the electron transfer has also attracted significant research by electrochemical reactions of neutral and controls the reaction pathway. interest. organic compounds. Carbocations, Such a functional group is called an carbon free radicals, and carbanions electroauxiliary. Use of electroauxiliaries Synergy Between Organic can also be generated by subsequent enables selective electrochemical Electrochemistry and bond-dissociation or bond-forming transformations that are difficult to processes. One of the major advantages achieve by conventional ways. Microreactors of the electrochemical method is the Reaction media.—Reaction media such absence of byproducts derived from as solvents and supporting electrolytes Though organic electrochemistry chemical reagents that are needed for play important roles in organic serves as a powerful method for organic the chemical method. Therefore, the electrochemistry. Recent developments synthesis, there are some problems electrochemical method provides a enable the use of ionic liquids and inherent in conducting electrode better environment for subsequent supercritical fluids as solvents for processes in organic solvents. For reactions of thus-generated reactive electrolysis. Solid-supported electrolytes example, conductivity of common species. These reactive carbon species and mediators have also been developed. organic solvents is low. Therefore, cell have been utilized in various synthetic An interesting method, in which the voltage is usually higher than that for transformations, especially carbon- electrolysis can be conducted under aqueous systems. Reactions on the carbon bond formations. Oxidation homogeneous traditional conditions yet surface of the electrodes suffer from and reduction of functional groups the products can still be easily separated low mass transfer problem causing are also important transformations in from the reaction media by simple smaller productivity compared with operations, is also noteworthy. homogeneous chemical reactions. Therefore, the design of appropriate devices for electrolysis is very important. Use of organic salts such S iM e3 as tetraalkylammonium salts that are - 2e soluble in organic solvents as supporting N electrolytes also causes a problem of N + -72 oC- r.t. N B u 4 NB F 4 separation and recycling after the CO M e CO 2M e 2 CH C l CO 2M e electrolysis. Such issues might be a 2 2 barrier to applications of the organic -72 oC electrochemistry in synthesis and " c ati on p ool"