Domestic Microwave Ovens

A solution of a benzene-1,2-diaminc (15mmol) and an cnol ether 4 (15mmol) in o-xylene (lOmL) was heated in a domestic microwave oven for a specified time. The reaction mixture was cooled and evaporated under reduced pressure, and the residue was purified by chromatography (silica gel. hexane/ CHCl3 1 4). 

The domestic microwave oven is one of the magnificent inventions used in the kitchen that contributes to simplify ing the lives of many people, as the time for cooking an acceptable meal can be reduced to the time it takes to defrost and heat vacuum-packed food, altogether consuming less than half an hour. 

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. 

Li and co-workers introduced a rapid and efficient microwave-assisted method to prepare new disubstituted 1,3,4-thiazoles from 1,4-disubtituted thiosemicarbazides with the objective to obtain biologically active molecules. The intermediate l-aryloxyacetyl-4-(4-methoxybenzoyl)thiosemicarbazide was irradiated in an excess of glacial acetic acid in a domestic microwave oven and led to the formation of 2-(methoxybenzoyl-5-aryloxymethyl)-l,3,4-dithiazoles in good yields [30] (Scheme 20). 

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... 

Independently, Caddick et al. reported microwave-assisted amination of aryl chlorides using a palladium-N-heterocyclic carbene complex as the catalyst (Scheme 99) [lOlj. Initial experiments in a domestic microwave oven (reflux conditions) revealed that the solvent is crucial for the reaction. The Pd source also proved very important, since Pd(OAc)2 at high power in DMF gave extensive catalyst decomposition and using it at medium and low power gave no reaction at all. Pd(dba)2/imidazohum salt (1 mol% catalyst loading) in DME with the addition of some DMF was found to be suitable. Oil bath experiments indicated that only thermal effects are governing the amination reactions. 

The first report appeared in 1999 when Banks described the basic reaction of 2,5-hexanedione and aniline, which was successfully carried out mixing the neat reagents and irradiating for 30 s in a domestic microwave oven. Several 2,5 dimethypyrroles 9 were prepared starting from the same 1,4 diketone [30] (Scheme 3). 

Many organic reactions can be conducted very rapidly under microwave irradiation. Microwave-induced organic reaction enhancement chemistry techniques were used for the rapid formation of an ot-benzyloxy-p-lactam (10 in Fig. 4.2) and the hydrogenolysis of its benzyloxy group on a few-gram scale in 1-5 minutes with HC02NH4 and Pd/C in ethylene glycol as the reaction medium in a domestic microwave oven.243... 

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. 

Operating with chemicals and pressurized containers always carries a certain risk, but the safety features and the precise reaction control of the commercially available microwave reactors protect the users from accidents, perhaps more so than with any classical heating source. The use of domestic microwave ovens in conjunction with flammable organic solvents is hazardous and must be strictly avoided as these instruments are not designed to withstand the resulting conditions when performing chemical transformations. 

The reactions were carried out rapidly in a modified domestic microwave oven with mountings in the side wall for sufficient inert gas supply. Furthermore, a dedicated custom-made solid-phase reaction vessel was employed under atmospheric pressure conditions. 

For the preparation of the triazine membranes, the entire solid support (cellulose or polypropylene membrane) was treated with a 5 m solution of the corresponding amine in l-methyl-2-pyrrolidinone (NMP) and a 1 m solution of cesium phenolate in dimethyl sulfoxide (2 p L of each at one spot) and subsequently heated in a domestic microwave oven for 3 min. After washing the support successively with... 

In closely related work, similar solid-phase chemistry was employed by the same research group to prepare biaryl urea compound libraries by microwave-assisted Suzuki couplings followed by cleavage from the resin with amines (Scheme 7.47) [18]. The above described procedure enabled the generation of large biaryl urea compound libraries employing a simple domestic microwave oven. 

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. 

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