Microwave activation

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

Microwave activation in phase-transfer catalysis of formation of heterocycles 99T10851. 

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

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. 

Hydroformylation of alkenes can be carried out in a few minutes under microwave activation at a relatively low pressure (2.7 bar) employing the rhodium(I)/XANTPHOS catalyst. The presence of the ionic liquid butyl-methylimdazolium tetrafluoroborate ([bmim][BF4]) was crucial. Unfortu-... 

These procedures coupled with microwave activation have proven beneficial and have led to many success stories which are described in several reviews [3, 4, 39-42]. 

The preparation of aliphatic, aromatic, or functionalized tartramides directly from tartaric acid and amines under solvent-free conditions and microwave activation was very recently described [67 b],... 

Alkylations in dry media of the ambident 2-naphthoxide anion were performed under the action of focused microwave activation. Whereas the yields were identical to those obtained under the action of A for benzylation, they were significantly improved under microwave irradiation conditions for the more difficult n-octylation (a less reactive electrophilic reagent). No change in selectivity was observed, however, indicating the lack of influence of ionic polarization [94],... 

The microwave-assisted PTC transesterification of several carbohydrates in basic medium with methyl benzoate or laurate has been studied [96], Small amounts of DMF were necessary to provide good yields within 15 min at 160 °C. Rate enhancements were compared to conventional heating (A) under the same conditions and specific microwave activation was mostly seen when the less reactive fatty compounds were involved (Eq. (44) and Tab. 3.19)... 

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] ... 

It must be stressed that a liquid component can be substituted with an efficient absorber of microwave irradiation together with a low-melting component. The use of most typical PTC solvents (nonpolar aromatic or aliphatic hydrocarbons, or highly chlorinated hydrocarbons) is most interesting for microwave activation, because such solvents are transparent or absorb microwaves only weakly. They can, therefore, enable specific absorption of microwave irradiation by the reagents, and the results or product distributions might be different under microwave and conventional conditions [7]. 

Because microwave activation is rather a new technique, the number of examples might seem limited at the present time it is, however, increasing rapidly. 

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. 

Rapid monoalkylations are achieved in good yield compared with classical methods. Of particular interest is the synthesis of ot-amino acids by alkylation of aldimines with microwave activation. Subsequent acidic hydrolysis of the alkylated imine provides leucine, serine, or phenylalanine in preparatively useful yields within 1-5 min [50], Alkylation of phenylacetonitrile was performed by solid-liquid PTC in 1-3 min under microwave irradiation (Eq. 36 and Tab. 5.14). The nitriles obtained can subsequently be quickly hydrolyzed in a microwave oven to yield the corresponding amides or acids [56]. 

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],... 

This study was next extended to the synthesis of benzoyl and dodecanoyl derivatives from protected carbohydrates [67]. Microwave-assisted PTC transesterifications with methyl benzoate or dodecanoate were studied for several carbohydrates. Small amounts of dimethylformamide (DMF) were shown to be necessary to provide good yields (76-96%) within 15 min. Rate enhancements when compared to conventional heating (A) and specific microwave activation were especially noticeable when less reactive fatty compounds were involved (Eq. 48). 

As described earlier (Sect. 6.2.4.6), the solid reagent system, IBD-alumina, is a useful oxidizing agent and its use is extendible to rapid, high yield and selective oxidation of alkyl, aryl and cyclic sulfides to the corresponding sulfoxides upon microwave activation (Scheme 6.35) [110]. 

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 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. 

Alkylation of 31 with dibromomethane and 1,2-dibromoethane was performed under solvent-PTC conditions with good yields and short irradiation times (15 min) [16]. The synthesis of original benzimidazo-[l,2-c]-quinazoline dimers 32(a,b) was successfully achieved by use of potassium carbonate in the microwave active DMF solvent (Scheme 8.13). 

A simple and rapid synthesis of tetrapyrrolic macrocycle has been achieved under dry media conditions with microwave activation. Pyrrole and benzaldehyde adsorbed on silica gel afford tetraphenylporphyrin within 10 min (Scheme 8.26), whereas with conventional methods (e. g. acetic acid in the presence of pyridine) 24 h were necessary. 

Cineole derivatives, of interest as potential cosmetic products, were obtained under a green chemistry procedure , i. e. one without solvent, with microwave activation according to Scheme 8.54. 

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]. 

Solvent-free conditions are especially suitable for microwave activation. Several advantages of this approach are evident [22] ... 

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]. 

As an example, the microwave activation of the platinum catalyst under conditions when it was highly sensitive to thermal treatment resulted in an increase of its catalytic activity and selectivity (from 40 to 80%) [28]. 

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. 

Microwave activation of alkane transformations was studied in detail by Roussy et al., who summarized their results in several papers [2, 28, 29, 79]. Isomerization of hexane, 2-methylpentane, 2-methyl-2-pentene, and hydrogenolysis of methylcydo-pentane have been investigated, and the diversity of possible effects has been specified [2]. The course of 2-methylpentane isomerization on a 0.3% Pt/Al203 catalyst depended on the mode of heating - the distribution of hexane products was different... 

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