Microwave oven synthesis

Bose, A.K., Manhas, M.S., Ghosh, M., Raju, V.S., Tabei, K. andUrbanczyk-Lipkowska, Z., Highly accelerated reactions in a microwave oven synthesis of heterocycles, Heterocycles, 1990, 30, 471. 

Appiication of commerciai microwave ovens to organic synthesis [103]... 

The rapid synthesis of heteroaromatic Hantzsch pyridines can be achieved by aromatization of the corresponding 1,4-DHP derivative under microwave-assisted conditions [51]. However, the domino synthesis of these derivatives has been reported in a domestic microwave oven [58,59] using bentonite clay and ammoniiun nitrate, the latter serving as both the source of ammonia and the oxidant, hi spite of some contradictory findings [51,58,59], this approach has been employed in the automated high-throughput parallel synthesis of pyridine libraries in a 96-well plate [59]. In each well, a mixture of an aldehyde, ethyl acetoacetate and a second 1,3-dicarbonyl compound was irradiated for 5 min in the presence of bentonite/ammonium nitrate. For some reactions, depending upon the specific 1,3-dicarbonyl compound used. 

This transformation can also be carried out under solvent-free conditions in a domestic oven using acidic alumina and ammoniiun acetate, with or without a primary amine, to give 2,4,5-trisubstituted or 1,2,4,5-tetrasubstituted imidazoles, respectively (Scheme 15A) [69]. The automated microwave-assisted synthesis of a library of 2,4,5-triarylimidazoles from the corresponding keto-oxime has been carried out by irradiation at 200 ° C in acetic acid in the presence of ammonium acetate (Scheme 15B) [70]. Under these conditions, thermally induced in situ N - O reduction occurs upon microwave irradiation, to give a diverse set of trisubstituted imidazoles in moderate yield. Parallel synthesis of a 24-membered library of substituted 4(5)-sulfanyl-lff-imidazoles 40 has been achieved by adding an alkyl bromide and base to the reaction of a 2-oxo-thioacetamide, aldehyde and ammonium acetate (Scheme 15C) [71]. Under microwave-assisted conditions, library generation time was dramatically re-... 

With a similar approach, Dave and Shah have developed a simple, fast, solvent-free and high-yielding, variant of the Gould-Jacob type synthesis of thieno[3,2-e]pyrimido[l,2-c]pyrimidines. In this example the conventional condensation between 4-aminothieno-2,3-dyrimidines and diethyl ethoxymethylenemalonate via acyclic intermediates (usually performed in 5-6 h) was compared with a solvent-free single-step microwave procedure (7-10 min) applying a multimode microwave oven (BPL 700T, Mumbai, India) [7], Scheme 6. 

A solvent-free strategy for the synthesis of thiazoles involved mixing of thioamides with a-tosyloxy ketones in a clay-catalyzed reaction (Scheme 7). The typical procedure entailed mixing of thioamides and in situ produced a-tosyloxy ketones with montmorillonite K-10 clay in an open glass container. The reaction mixture was irradiated in a microwave oven for 2-5 min with intermittent irradiation and the product was extracted into ethyl acetate to afford 2-substituted thiazoles in 88-96% yields [8]. 

In addition, thionation-cyclisation of 1,2-diacylhydrazidines to 1,3,4-thiadiazoles has been achieved by the action of Lawesson s reagent under solvent-free microwave irradiation in a domestic microwave oven (Scheme 21). This ring-closure methodology was extended for the synthesis of various liquid crystals [1]. 

Since 1986, when the very first reports on the use of microwave heating to chemical transformations appeared [147,148], microwave-assisted synthesis has been shown to accelerate most solution-phase chemical reactions [24-27,32,35]. The first application of microwave irradiation for the acceleration of reaction rate of a substrate attached to a solid support (SPPS) was performed in 1992 [36]. Despite the promising results, microwave-assisted soHd-phase synthesis was not pursued following its initial appearance, most probably as a result of the lack of suitable instriunentation. Reproducing reaction conditions was nearly impossible because of the differences between domestic microwave ovens and the difficulties associated with temperature measurement. The technique became a Sleeping Beauty interest awoke almost a decade later with the publication of several microwave-assisted SPOS protocols [37,38,73,139,144]. There has been an extensive... 

The use of microwave ovens in organic synthesis including catalytic organic reactions has also been of considerable recent interest. (4) Primarily this... 

In this study we show that the Pd/C catalyzed Suzuki-Miyaura coupling reaction can be performed in a microwave oven. Overall the microwave synthesis is faster than comparable thermal methods and the combination of the ease of use of the microwave oven and the facile work-up with Pd/C makes this a very efficient method for performing coupling reactions. 

A solvent-free synthesis of benzo[b]furan derivatives 10-79, a class of compounds which is often found in physiologically active natural products, was described by Shanthan Rao and coworkers. These authors heated phosphorane 10-71 for 8 min in a microwave oven and obtained the benzo[b]furan 10-74 in 73% yield (Scheme 10.18) [25]. The sequence is initiated by an intramolecular Wittig reaction, providing alkyne 10-72 this underwent a subsequent Claisen rearrangement to give the intermediate 10-73. Also in this case, normal oil-bath heating gave much lower yields (5%) of the desired product the authors hypothesize that the micro-... 

The synthesis of carbon templated mesoporous tin MFI catalysts with different Si/Sn was carried out using microwave and in typical synthesis methodology TEOS, TPAOH, [Sn(C5H70)2]2]Cl2, ethanol and water were employed where the molar composition of the reaction mixture was 0.06 TPAOH 0.67 H20 0.028 TEOS 1.3 g EtOH X mg of tin precursor (X = 85, 63, 42, 21 mg). This synthesis mixture was stirred for 90 min at room temperature and then Black pearl 2000 carbon (10% wt. of TEOS) was added and again stirred for 4 h vigorously. The crystallization of C-meso-Sn-Silicalite was performed in a Teflon cup placed in a microwave oven (MARS-5, CEM, maximum power of 1200 W). 

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],... 

Since the early applications of microwave-assisted synthesis were based on the use of domestic multimode microwave ovens, the primary focus in the development of dedicated microwave instruments was inevitably the improvement of multimode... 

Other microwave-assisted parallel processes, for example those involving solid-phase organic synthesis, are discussed in Section 7.1. In the majority of the cases described so far, domestic multimode microwave ovens were used as heating devices, without utilizing specialized reactor equipment. Since reactions in household multimode ovens are notoriously difficult to reproduce due to the lack of temperature and pressure control, pulsed irradiation, uneven electromagnetic field distribution, and the unpredictable formation of hotspots (Section 3.2), in most contemporary published methods dedicated commercially available multimode reactor systems for parallel processing are used. These multivessel rotor systems are described in detail in Section 3.4. 

Several articles in the area of microwave-assisted parallel synthesis have described irradiation of 96-well filter-bottom polypropylene plates in conventional household microwave ovens for high-throughput synthesis. While some authors have not reported any difficulties in relation to the use of such equipment (see Scheme 4.24) [77], others have experienced problems in connection with the thermal instability of the polypropylene material itself [89], and with respect to the creation of temperature gradients between individual wells upon microwave heating [89, 90]. Figure 4.5 shows the temperature gradients after irradiation of a conventional 96-well plate for 1 min in a domestic microwave oven. For the particular chemistry involved (Scheme 7.45), the 20 °C difference between the inner and outer wells was, however, not critical. 

Several microwave-assisted protocols for soluble polymer-supported syntheses have been described. Among the first examples of so-called liquid-phase synthesis were aqueous Suzuki couplings. Schotten and coworkers presented the use of polyethylene glycol (PEG)-bound aryl halides and sulfonates in these palladium-catalyzed cross-couplings [70]. The authors demonstrated that no additional phase-transfer catalyst (PTC) is needed when the PEG-bound electrophiles are coupled with appropriate aryl boronic acids. The polymer-bound substrates were coupled with 1.2 equivalents of the boronic acids in water under short-term microwave irradiation in sealed vessels in a domestic microwave oven (Scheme 7.62). Work-up involved precipitation of the polymer-bound biaryl from a suitable organic solvent with diethyl ether. Water and insoluble impurities need to be removed prior to precipitation in order to achieve high recoveries of the products. 

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]. 

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