Microwave activated reaction

A recent report [6] has discussed the effect of monomode microwave irradiation in the palladium-catalyzed phenylation of 5-iodouracil 4 with the nontoxic sodium tet-raphenylborate 5 as phenyl reagent (Scheme 8.3). The authors showed that the use of monomethylformamide (MMF) as solvent increases the yield of 6 (70%), because MMF has a high boiling point (180 °C) and is more polar (s = 182.5) than other amides used in microwave-activated reactions. 

For the development of a sustainable chemistry based on clean technologies, the best solvent would be no solvent at all. For this reason, considerable efforts have recently been made to design reactions that proceed under solvent-free conditions, using modern techniques such as reactions on solid mineral supports (alumina, silica, clays), solid-state reactions without any solvent, support, or catalyst between neat reactants, solid-liquid phase-transfer catalysed and microwave-activated reactions, as well as gas-phase reactions [37-42]. However, not all organic reactions can be carried out in the absence of a solvent some organic reactions even proceed explosively in the solid state Therefore, solvents will still be useful in mediating and moderating chemical reactions and this book on solvent effects will certainly not become superfluous in the foreseeable future. 

No solvent at all [i.e. solvent-free reactions) All solvents Many types of reactions, using the following techniques Reactions on solid mineral supports (alumina, silica, clays) without any solvent, support, or catalyst between neat reactants solid-liquid phase-transfer-catalyzed and microwave-activated reactions ... 

Microwave activation of reactions of heterocycles 98S1213, 99T10851. 

Microwave-activated Dieis-Aider cycioaddition reactions of 1,2-difiuoro-1-chiorovinyi-phenyisuifone [102]... 

Oxazoles have attracted considerable interest due their presence as subunits of several biologically active compoimds or as rigid mimetics of a peptidic ring. A first synthesis of 2-phenyl-4,5-substituted oxazoles 54 [47] was described by microwave-assisted reaction of enolizable ketones with benzoni-trile in the presence of mercury(II) p-toluenesulfonate (Scheme 17). 

Finally, a series of 2-chloromethyl-5-aryl-1,3,4-oxadiazoles 82 were prepared by reaction of aromatic hydrazides 81 and a chloromethylorthofor-mate used as the solvent under microwave activation [62]. Potentially, the chloromethyl group could imdergo nucleophiUc substitution expanding the scope of this reaction (Scheme 28). 

Allylation of acyloyl-imidazoles and pyrazoles61 with allyl halide mediated by indium in aqueous media provides a facile regioselective synthesis of P, y-unsaturated ketones (Scheme 11.1), which has been applied to the synthesis of the monoterpene artemesia ketone. The same product can be obtained by indium-mediated allylation of acyl cyanide (Eq. 11.35).62 Samarium, gallium, and bismuth can be used as a mediator for the allylation of nitrones and hydrazones to give homoallylic hydroxylamine and hydrazides in aqueous media in the presence of Bu4NBr (Scheme 11.2).63 The reaction with gallium and bismuth can be increased dramatically under microwave activation. 

A decrease in the activation energy AG is certainly a major effect. Because of the contribution of enthalpy and entropy to the value of AG (= AH -TAS ), it might be predicted that the magnitude of the -TAS term would increase in a microwave-induced reaction, because organization is greater than with classical heating, as a consequence of dipolar polarization. 

A similar conclusion has been drawn during an examination of the Diels-Alder reaction of 6-demethoxy-/J-dihydrothebaine with methylvinylketone using microwave irradiation [110]. When performed under conventional heating conditions, extensive polymerization of the dienophile was observed whereas reaction is much more cleaner under microwave activation (Eq. 61). 

PTC reactions are perfectly tailored for microwave activation, and combination of solid-liquid PTC and microwave irradiation gives the best results in this area [8] ... 

In conventional methods, PTC has provided interesting procedures for O-alkylation, and coupling PTC conditions with microwave activation has proved to be quite fruitful for such reactions. 

The diethers were synthesized in high yield within short reaction times. When compared with classical heating, under otherwise comparable conditions, reactions times were improved by microwave activation. 

Microwave activation and solvent-free PTC have been shown to be of prime efficiency for the synthesis of new benzylidene cineole derivatives (UV sunscreens) by the Knoevenagel reaction. When performed classically by use of KOH in ethanol at room temperature for 12 h (Eqs. 43 and 44) the yield was 30%. This was improved to 90-94% within 2-6 min under PTC + MW conditions (Tabs 5.17 and 5.18) [27, 28],... 

The efficiency of fluorous Stille coupling reactions [5 a] is enhanced by use of microwave irradiation (Scheme 8.2). The reaction proceeds in 79% yield after 2 min with DMF as the microwave-active solvent. 

A survey of microwave activation in the chemistry of Hantzsch 1,4-dihydropyridines (1,4-DHP) has recently been reported [98]. The experimental method proposed more than a century ago remains the most widely used to synthesize these heterocycles. Since 1992 this process has been adapted to microwave irradiation under a variety of conditions to reduce the reaction time and enhance the yield. Among these experiments, Zhang [99] reported a solvent-free process starting from 3-aminocrotonate... 

Cycloaddition reactions often require the use of harsh conditions such as high temperatures and long reaction times. These conditions are not compatible with sensitive reagents or products such as natural products. The applicability of Diels-Alder cycloadditions is, moreover, limited by the reversibility of the reaction when a long reaction time is required. The short reaction times associated with microwave activation avoid the decomposition of reagents and products and this prevents polymerization of the diene or dienophile. All these problems have been conveniently solved by the rapid heating induced by microwave irradiation, a situation not accessible in most classical methods. With the aid of microwave irradiation, cydoaddition reactions have been performed with great success [9, 10]. 

Sandhu reported that conjugated nitrones react with unactivated alkenes under microwave activation more rapidly (6-15 min) than in the corresponding thermolytic or sonochemical reactions [32 a],... 

Microwave radiation can be used to prepare new catalysts, enhance the rates of chemical reactions, by microwave activation, and improve their selectivity, by selective heating. The heating of the catalytic material generally depends on several factors including the size and shape of the material and the exact location of the material in the microwave field. Its location depends on the type of the microwave cavity used [2]. 

Some reactions have been found to proceed with better results in the absence of solvent, probably because of the creation of temperature gradients which are eliminated in the presence of a stirred solvent. This was observed for the Diels-Alder reaction of a-amino acid precursors with cyclopentadiene catalyzed by heterogeneous catalysts (Si02-Al, Si02-Ti), when the reaction was performed in toluene or in the absence of solvent [53], Microwave activation increased the rate of reaction without reducing the selectivity of the reaction. 

The microwave activation of Michael additions in the preparation of N-substituted imidazoles afforded excellent yields in very short reaction times under mild reaction conditions, Scheme 10.9. Basic clays (Li+, Cs+) exchanged montmorillonites were found to be very active and selective catalysts for the Michael addition of imidazole and ethyl acrylate [54]. 

A detailed study of microwave activation of catalytic reactions in the liquid phase has recently been performed by Hajek et al. [58-60], Scheme 10.13. 

Although microwave activation of catalytic reactions has been the subject of many studies (Sects. 10.3.1 and 10.3.2), the mechanism of these reactions is not yet fully understood. In heterogeneous catalytic liquid/solid and gas/solid systems many results have revealed significant differences between the rates of conventionally and microwave heated reactions. As a rule, at the same temperature microwave heated reactions were faster than conventional and their rate enhancement was over one or-... 

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