Synthetic Applications for Microwave Synthesis

As microwave synthesis instrumentation continues to evolve, new applications will be developed for a variety of chemistries and process developing needs.

In the past five years, there has been an increased demand for large collections of novel drug targets. The long reaction times that are required for conventional heating have led to the advent of new technologies, including combinatorial and parallel chemistry. Combinatorial chemistry allows a chemist to synthesize large libraries of molecules by varying combinations and permutations of different components. Recently, there has been a shift towards parallel synthesis, primarily due to problems with deconvolution of complex combinatorial mixtures. These technologies still require classical thermal heat. The use of microwave chemistry in organic synthesis has now introduced a completely new approach to drug discovery. Microwave systems provide the opportunity to complete reactions in minutes, offering the option to return to more sequential methods. This is advantageous because it allows chemists to analyze a reaction before conducting the next step, enabling them to optimize their reactions and their time. This chapter will document the many synthetic applications that have benefited from the use of microwave irradiation. Note: The reader should assume that all reaction schemes shown in this chapter utilize microwave irradiation. In multi-step schemes, the use of microwave energy is indicated by “microwaves” on the arrow.

A majority of the applications found in this chapter have been performed in a multi-mode microwave cavity under atmospheric conditions or in sealed glass or TeflonTM vessels, as single-mode reactors may not have been available at the time the work was completed. The rates of reactions performed in a multi-mode cavity are greater than those using conventional methods, but repeatability is low. The reader should also be aware that multi-mode instruments require a lot of power because of their spacious cavity. The total power generated is high, but the power density in the cavity is quite low. A higher power density allows the energy to be more focused in single-mode instrumentation, and 300 W or lower is sufficient. A chemist looking to mimic the conditions found in the references should concentrate on the temperature needed and not the power level.

Chemists have been conducting research in micro-wave synthesis since the mid-1980s. As a result, there are many articles on the multitude of reactions that can be performed with microwave energy. Older reviews on microwave-enhanced synthetic applications include those by Abramovitch296, Caddick382, Majetich and co-workers10,223,182, Sridar294, and a more recent review by Lidstrom et al.183 As microwave synthesis continues to grow in popularity, the applications written for it will multiply as well, though there are many types of reactions investigated in current literature including organometallic, cycloaddition, heterocyclic, oxidations, and condensations.