chimica oggi • Chemistry Today • Vol 24 nr 3 • May/June 2006 30 Microwaves Microwaves in chemistry: the success story goes on FRANK WIESBROCK ULRICH S. SCHUBERT ABSTRACT Within two decades, microwave reactors have been established in laboratories world-wide. After the successful exploration of accelerations of reactions under microwave irradiation, current research interests additionally cover the investigation of alternative reaction pathways under microwave conditions, yielding products that cannot be obtained with conventional heating. Microwave reactors have been successfully used in particular in the field of high-throughput experimentation, further decreasing the time to find best-suited candidates for certain applications. The resulting request for scale-up microwave reactors has been answered by the commercial release of the first devices. INTRODUCTION After their victorious procession through households worldwide, microwave reactors have also been established as fast and efficient heating devices in virtually every field of chemical synthesis over the last years. Microwaves have frequencies in the range from 300 GHz to 300 MHz (corresponding to wavelengths in the range from 1 mm to 1 m) and, consequently, are in the region between infrared and radio waves. Commercial microwave reactors, the kitchen-type ovens as well as the reactors specially-designed for operation in laboratories, operate with a standardized uniform frequency of 2450 MHz (corresponding to a wavelength of 12.24 cm) to avoid interference with telecommunication devices. The electric fields oscillate 4.9 10 9 times per second. Dipoles and ions (as well as electrons and electron holes in metals) try to align to these electromagnetic fields and therefore are subjected to periodical reorientation. During this process, energy is lost and dissipated as heat to the environment through molecular friction and ionic conduction. As a result, microwave-assisted heating works best in polar and ionic solutions/suspensions. The use of microwaves as alternative heating source provides so-called internal heating as heat is directly generated within the reaction mixture itself. Assuming uniform penetration of the reaction mixture by microwaves and efficient mixing of the reaction components, the heating of reaction mixtures by microwaves is gradient-free. This gradient-free heating keeps undesired side-reactions at a minimum and therefore is one major advantage over conventional conductive heaters like Bunsen burners, hot plates or oil baths where the heating source is in direct contact with the reactors and induces temperature gradients from the hot outer walls of the reactor to its (comparably) cold centre. In the case of internal microwave-assisted heating, on the other hand, the walls of the reactor are colder than the centre of the reactor (inverted heating profile). This non-contact heating by microwaves also provides fast heating because it is direct (no detour over the reactor walls for heat transfer). This bundle of advantages of microwave-assisted heating over conventional heating continuously raises the interest of synthetic chemists. However, only after the advent of specially designed microwave reactors (single-mode as well as multi-mode reactors) (1-4) with control devices (that allow to control the self-acceleration of exothermic reactions) some years ago, microwave-assisted heating has become a serious alternative to conventional heating in chemical synthesis, in particular in organic and pharmaceutical synthesis. A large collection of data referring to microwave-assisted reactions is available these days, and a selection of these applications will be highlighted in this review to show the possible future directions in the field of microwave- enhanced chemistry. For general reviews, the reader is referred to some recent comprehensive reviews (5-13). Alternative reaction pathways under microwave irradiation The comparison of reactions under microwave irradiation with those under conventional heating exhibits accelerations of the reactions under microwave irradiation as well as alternative product distributions and even the formation of alternative products for a large number of examples. A discussion has arisen whether microwave effects exist or not (6, 13, 14). In particular after the advent of microwave reactors specially-designed for chemical reactions with properly-suited devices for the measurement of temperatures (1-4), it could be shown for the accelerations that they are likely to originate from the high temperatures/pressures accessible under microwave irradiation. The temperatures accessible in microwave reactors may significantly exceed the boiling point of the solvent(s)/reactants (pressures of 20 bar (1-3) or even higher (4) still enable safe operation). According to the Arrhenius equation, a reaction will be accelerated by a factor of two if the bulk temperature is increased by 10 K (“rule of thumb”), which yields an acceleration factor of approximately 1000 (e.g., 2 days → 3 min) if a reaction in aqueous solution is performed at 200 °C instead of 100 °C. Assuming that neither the activation energy nor the frequency factor change upon switching from conventional to microwave-assisted heating, accelerations of the same magnitude could be achieved under conventional autoclave conditions. However, due to the intrinsic properties of microwave irradiation, it has been argued that the frequency factor may alter if the respective reactants are exposed to an electromagnetic field of microwaves (15, 16). This type of accelerations cannot be realized under conventional heating. Microwave-specific accelerations are also