Assisted Organic Synthesis

MICROWAVE-ASSISTED ORGANIC SYNTHESIS Microwaves and Their Heating Effect 

Microwave irradiation has been widely used in organic synthesis on a laboratory scale during the last few years. Several categories of reactions, for example, Diels-Alder reactions, ortAo-Claisen condensations, ene-reactions, oxidations, esterification of carboxylic acids with alcohols, and hydrolysis of esters and amides to carboxylic acids, have been successfully carried out in conventional microwave ovens. Table 26.4, adapted from Majetich and Hicks (1994), provides representative examples of some of these reactions. It can be seen that the conditions under which the conventional and microwave reactions are carried out differ significantly for most reactions. Hence, in comparing reactions with micro-waves with conventional syntheses with reflux, it is necassary to make the comparisons based on the total amount of energy input to the reaction volume. 

Solvent Methanol Reaction temp reflux (65 °C) Yield 92% 

Solvent Methanol-water Reaction temp reflux (79 °C) Yield 60% 

Solvent Ethanol Reaction temp reflux (78 °C) Yield 89% 

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Program systems for computer-assisted organic synthesis (CAOS) have been under development since the early 1970s [27]. The program systems for computer-assisted synthesis planning can be subdivided into two groups information-oriented and logic-oriented systems [28]. 

Computer-Assisted Organic Synthesis W. T. Wipke, W. J. Howe, Eds., ACS, Washington (1977). 

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. 

For recent reviews on microwave irradiation-assisted organic synthesis, see Kuhnert, N., Angew. Chem., hit. Ed. 2002, 41, 1863 Lidstrom, P Tierney, J., Wathey, B Westman, J., Tetrahedron 2001, 57, 9225. 

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... 

Hladka, E., Koca, J., Kratochvil, M., Kvasnicka, V., Matyska, L., Pospichal, J. and Potucek, V. The Synthon Model and the Program PEGAS for Computer Assisted Organic Synthesis. 166, 121-197 (1993). 

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. 

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