Microwave chemistry

Microwave chemistry has been found to be a useful method for accelerating reactions or catalyzing reactions that are difficult to carry out by other methods. A modification of the Hantzsch method to directly obtain pyridines has been communicated. A dry medium using ammonium nitrate bentonitic clay system with microwave irradiation affords pyridines 96 in a single pot within 5 minutes. When the pyridine is not the major product (> 75% yield), the dealkylated pyridine 97 becomes an... 

The strategies explored and defined in the various examples presented open a way for wider application of microwave chemistry in industry. The most important problem for chemists today (in particular, drug discovery chemists) is to scale-up microwave chemistry reactions for a large variety of synthetic reactions with minimal optimization of the procedures for scale-up. At the moment, there is a growing demand from industry to scale-up microwave-assisted chemical reactions, which is pushing the major suppliers of microwave reactors to develop new systems. In the next few years, these new systems will evolve to enable reproducible and routine kilogram-scale microwave-assisted synthesis. 

In recent years, parallel to the emergence of SPOS, microwave-mediated organic synthesis has come to hght and has developed into a popular field [24-31]. The main advantage of microwave dielectric heating compared to other conventional methods, such as hot plate, oil bath or isomantle, is the tremendous rate enhancement generally observed under microwave irradiation conditions. Various theories have been proposed to explain the source of the rapidity of microwave chemistry [32,33]. However, the gener-... 

PEG polymers are widely used as water soluble supports [99]. Although these polymers suffer from easy loss of PEG oligomers, they are frequently used for the preparation of small organic molecules [100-105] and biopolymers [106,107]. The main benefit of PEG supports is their solubility in water as well as most organic solvents. Also, as opposed to most solid-phase techniques, PEG polymers allow for easy on-bead NMR monitoring. Soluble PEG supports have been used frequently in synthetic microwave chemistry protocols [108-122]. 

Linear non-cross-linked polystyrene has been used for organic synthesis since it is readily soluble in common organic solvents (i.e., dichloromethane, chloroform, tetrahydrofuran, toluene, ethyl acetate, and pyridine) but precipitates upon addition of water or methanol [123-126]. However, no examples of the use of this polymer in conjunction with microwave chemistry have been reported. 

One of the reasons why there has been phenomenal growth in research in microwave chemistry since the early 1990s is the realization that it can provide a rapid method for screening reactions. With a heating rate of 10 °C per second being achievable it is easy to see how the overall reaction time can be considerably shortened. Although there are examples of... 

It should be obvious from a scientific standpoint that the question of microwave effects needs to be addressed in a serious manner, given the rapid increase in the use of microwave technology in chemical sciences, in particular organic synthesis. There is an urgent need to remove the black box stigma of microwave chemistry and to provide a scientific rationalization for the observed effects. This is even more important if one considers safety aspects once this technology moves from small-scale laboratory work to pilot- or production-scale instrumentation. 

As a starting point for reaction optimization, Biotage offers a microwave reaction database (Emrys PathFinder) with ca. 4000 validated entries for microwave chemistry performed with Biotage single-mode instruments. 

Microwave Chemistry and Solid-Phase Organic Synthesis... 

The functionalization of commercially available standard solid supports is of particular interest for combinatorial purposes to enable a broad range of reactions to be studied. Since these transformations usually require long reaction times under conventional thermal conditions, it was obvious to combine microwave chemistry with the art of resin functionalization. 

Apart from the traditional organic and combinatorial/high-throughput synthesis protocols covered in this book, more recent applications of microwave chemistry include biochemical processes such as high-speed polymerase chain reaction (PCR) [2], rapid enzyme-mediated protein mapping [3], and general enzyme-mediated organic transformations (biocatalysis) [4], Furthermore, microwaves have been used in conjunction with electrochemical [5] and photochemical processes [6], and are also heavily employed in polymer chemistry [7] and material science applications [8], such as in the fabrication and modification of carbon nanotubes or nanowires [9]. 

Our main motivation for writing Microwaves in Organic and Medicinal Chemistry derived from our experience in teaching microwave chemistry in the form of short courses and workshops to researchers from the pharmaceutical industry. In fact, the structure of this book closely follows a course developed for the American Chemical Society and can be seen as a compendium for this course. It is hoped that some of the chapters of this book are sufficiently convincing as to encourage scientists not only to use microwave synthesis in their research, but also to offer training for their students or co-workers. 

In conclusion, is it necessary to obtain a microwave athermal effect to justify microwave chemistry Obviously not - it is not necessary to present microwaves effects in a scientific disguise. There are many examples in which microwave heating results in specific time-temperature histories and gradients which cannot be achieved by other means especially for solid materials. Hence, rather than claiming nonther-mal effects it is better to claim a means or a tool which induces a specific thermal history. 

Synthetic chemists desire well defined reaction conditions. Process chemists demand them. Nonuniform heating and difficulties with mixing and temperature measurement are technical constraints that initially limited the scale of microwave chemistry with dry media and have not yet been overcome. Poor reproducibility also has been reported, probably resulting from differences in performance and operation of individual domestic microwave ovens [13-15]. Consequently, most, if not all, of the disclosed applications of dry media are laboratory-scale preparations. However, as discussed in other chapters, this does not prevent their being interesting and useful. 

Recent studies by Mingos and Whittacker into the optimum conditions have confirmed the benefits of pressurized systems for microwave chemistry [73]. 

Economic and safety considerations encourage minimal stockpiling of chemicals and avoiding transportation of hazardous substances. These increasing demands offer many opportunities for microwave chemistry in the development of environmentally benign methods for the preparation of intermediates, specialty chemicals and pharmaceuticals [6[. It appears likely that within the next few years, individual chemical reactors will be required for diverse tasks and will need to be easily relocated... 

A. Loupy, International Conference of Microwave Chemistry, Prague, Czech Republic, 6-11 Sept, 1998, plenary lecture PL2. 

Int. Conf. Microwave Chemistry, Antibes, France, 4-7 Sept. 2000, pp. 33-36. 

Vass, A. Toth, J. Pallai-Varsanyi, E. in Effect of Inorganic Solid Support for Microwave Assisted Organic Reactions, OR 19, presented at the Int. Conf. Microwave Chemistry, Prague, Czech Republic, Sept. 6-11,1998. 

Microwave Chemistry, Sept. 6-11,1998, Prague, Czech Republic. 

The development in microwave chemistry has been remarkable during the last few years from the first reports in which, typically, domestic ovens were used to modern applications with state-of-the-art single-mode cavities. We believe that it is today possible today to develop robust microwave-assisted methods for nearly any reaction that needs an external heat source and we have proved it is possible to perform transition-metal catalyzed reactions very cleanly and selectively. 

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