Microwave-assisted organic synthesis

Microwave-assisted synthesis is attractive to researchers for many reasons, including speed, yields, and the potential for reduced solvent use. Raman monitoring offers a convenient way to elucidate the chemical mechanism while instantly, continuously monitoring reaction kinetics. This enables rapid, data-driven process optimizations without concerns about safely and accurately sampling out of a microwave vessel stopped mid-reaction. Pivonka and Empheld of AstraZeneca Pharmaceuticals describe the continuous acquisition of Raman spectra of an amine or Knoevenagel coupling reaction in a sealed microwave reaction vessel at elevated temperatures and pressures [134]. 

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This chapter has taken the reader through a number of microwave-assisted methodologies to prepare and further functionalize 2-pyridone containing heterocycles. A survey of inter-, intramolecular-, and pericyclic reactions together with electrophilic, nucleophilic and transition metal mediated methodologies has been exemplified. Still, a number of methods remain to be advanced into microwave-assisted organic synthesis and we hope that the smorgasbord of reactions presented in this chapter will inspire to more successful research in this area. 

Tierney JP, Lidstroem P (eds) Microwave assisted organic synthesis. Blackwell Publishing Ltd, Oxford, UK... 

Swamy KMK, Yeh W-B, Lin M-J, Sun C-M (2003) Curr Med Chem 10 2403 CarUlo JR, Dfaz-Ortiz A, de la Hoz A, Moreno A, Gomez MV, Prieto P, Sanchez-Migalldn A, Vazquez E (2003) In Attanasi OA, Spinelli D (eds) Targets in heterocyclic systems, chemistry and properties. Italian Society of Chemistry, vol 7 Baxendale IR, Lee A-L, Ley SV (2005) In Tierney JP, Lidstrom P (eds) Microwave assisted organic synthesis, chap 6. Blackwell Publishing Ltd, Oxford, UK Kappe CO, Stadler A (2005) Microwaves in organic and medicinal chemistry, chap 7. Wiley, Weinheim... 

Keywords Copper MAOS (Microwave assisted organic synthesis) Nickel Palladium Transition-metal-mediated bond formation... 

LindstrOm P, Tierney JP (eds) (2005) Microwave-assisted organic synthesis. Black-well, Oxford... 

An additional interest in the appUcations of microwave-assisted organic synthesis is related to the possibility of having more rapid access to large libraries of diverse small molecules and heterocycUc compounds... 

HMPB 4-Hydroxymethyl-3-methoxyphenoxybutyric acid MAOS Microwave-assisted organic synthesis NBS AT-Bromosuccinimide NIS AT-Iodosuccinimide PIPE Poly(tetrafluroethylene)... 

Due to the importance of substituted 2-pyridones, many preparative methods have been reported (see Sect. 2.1), and some of these, but for from all, have been further developed into methods suitable for microwave-assisted organic synthesis (MAOS). Here we describe mainly methods performed with instruments specially designed for MAOS, thus excluding synthesis per-... 

P. Lindstrom, J. Tierney, B Wathey and J. Westerman, Microwave Assisted Organic Synthesis - A Review , Tetrahedron, 2001, 57, 9222. 

Komatsu K (2005) The Mechanochemical Solid-State Reaction of Fullerenes. 254 185-206 Kremsner JM, Stadler A, Kappe CO (2006) The Scale-Up of Microwave-Assisted Organic Synthesis. 266 233-278... 

Microwave-Assisted Organic Synthesis (MAOS) - A Brief History... 

Scheme 1.1 Hydrolysis of benzamide. The first published example (1986) of microwave-assisted organic synthesis.

Fig. 1.1 Publications on microwave-assisted organic synthesis (1986-2004). Cray graphs Number of articles involving MAOS for seven selected synthetic organic chemistry journals ( J. Org. Chem, Org. Lett., Tetrahedron, Tetrahedron Lett., Synth. Commun., Synthesis, Synlett ...

Today, a large body of work on microwave-assisted synthesis exists in the published and patent literature. Many review articles [8-20], several books [21-23], and information on the world-wide-web [24] already provide extensive coverage of the subject. The goal of the present book is to present carefully scrutinized, useful, and practical information for both beginners and advanced practitioners of microwave-assisted organic synthesis. Special emphasis is placed on concepts and chemical transformations that are of importance to medicinal chemists, and that have been reported in the most recent literature (2002-2004). The extensive literature survey is limited to reactions that have been performed using controlled microwave heating conditions, i.e., where dedicated microwave reactors for synthetic applications with adequate... 

Chapter 8) T. Besson, C. T. Brain, in Microwave-Assisted Organic Synthesis (Eds. ... 

P. Lidstrom, J. P. Tierney (Eds.), Microwave-Assisted Organic Synthesis, Blackwell Publishing, Oxford, 2005. 

For online resources on microwave-assisted organic synthesis (MAOS), see uwiv.maos.net. 

This chapter provides a detailed description of the various commercially available microwave reactors that are dedicated for microwave-assisted organic synthesis. A comprehensive coverage of microwave oven design, applicator theory, and a description of waveguides, magnetrons, and microwave cavities lies beyond the scope of this book. Excellent coverage of these topics can be found elsewhere [1—4]. An overview of experimental, non-commercial microwave reactors has recently been presented by Stuerga and Delmotte [4],... 

In modern microwave synthesis, a variety of different processing techniques can be utilized, aided by the availability of diverse types of dedicated microwave reactors. While in the past much interest was focused on, for example, solvent-free reactions under open-vessel conditions [1], it appears that nowadays most of the published examples in the area of controlled microwave-assisted organic synthesis (MAOS) involve the use of organic solvents under sealed-vessel conditions [2] (see Chapters 6 and 7). Despite this fact, a brief summary of alternative processing techniques is presented in the following sections. 

Heterocyclic scaffolds form the cores of many pharmaceutically relevant substances. Not surprisingly, therefore, many publications in the area of microwave-assisted organic synthesis, both from academia and industry, deal with the preparation of heterocycles [5], In this final section of this chapter, the description of heterocycle synthesis is structured according to ring-size and the number of heteroatoms in the ring. 

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