Domestic MW oven

Microwave (MW) oven. Various domestic MW ovens with an output power around 1000W are commonly used for AR-IHC worldwide, although numerous commercial MW ovens have been designed with controlled temperature. 

Although the ability of microwaves (MW) to heat water and other polar materials has been known for half a century or more, it was not until 1986 that two groups of researchers independently reported the application of MW heating to organic synthesis. Gedye et al. [1] found that several organic reactions in polar solvents could be performed rapidly and conveniently in closed Teflon vessels in a domestic MW oven. These reactions included the hydrolysis of amides and esters to carboxylic acids, esterification of carboxylic acids with alcohols, oxidation of alkyl benzenes to aromatic carboxylic acids and the conversion of alkyl halides to ethers. 

A mixture of 30 and 31 and a small amount of acetic acid in ethanol was heated to reflux in a domestic MW oven. A catalytic amount of piperidine was then added and... 

The reactions were performed in an open beaker using a domestic MW oven, and reaction times were reduced from 2-24 h of conventional reflux to 3-11 min under MW irradiation. 

Alvarez-Builla et al. [75] have shown that the stereochemical outcome of the MW-assisted addition of 2-aminothiophenol 50 to the glycidic ester 51 (Scheme 4.27) is affected by the nature of the solvent and by the MW power output. When the nonpolar solvent toluene was used, the cis isomer of the product 52 predominated, whereas in the presence of acetic acid the trans isomer was the chief product. Increasing the power level caused an increase in the proportion of the trans isomer when toluene was used as the solvent. The reactions were performed in open vessels in a domestic MW oven. 

The variability of domestic MW ovens, nonhomogeneity of the MW field, and difficulties in temperature measurement often make it difficult to obtain reproducible rates and yields [10], and this may partly explain why MW heating has not become... 

Additional reports on olefination reactions have appeared [64] including the preparation of several phosphonium salts using a domestic MW oven wherein the reaction of neat triphenylphosphine and organic halide shows remarkable rate enhancement in a pressure tube with a threaded Teflon cap [65]. 

Condensation of salicylaldehyde and its derivatives with a variety of esters of chloroacetic acids in the presence of TBAB led to the synthesis of benzo[b]furans by means of a solid-liquid PTC reaction under the action of microwave irradiation [39]. This was a modification of one of the most popular routes to substituted benzo[b]furans, i.e. O-alkylation of O-hydroxylated aromatic carbonyl compounds with a-halogenated carbonyl compounds then intramolecular condensation. The mixture of aldehydes and chloroacetic acid esters were absorbed on potassium carbonate then irradiated in an open vessel in a domestic MW oven for 8-10 min (Eq. 26). 

Rapid N-alkylation of saccharin sodium salt (Eq. 28) by a series of halides has been performed on silica gel in a domestic MW oven. TEBA was shown to provide a useful co-catalytic effect (Table 6.12). 

N-Substituted amides and lactams can be rapidly N-alkylated under solid-liquid PTC conditions with MW irradiation. The reactions were performed simply by mixing an amide with a 50% excess of an alkyl halide and a catalytic amount of TBAB. These mixtures were absorbed on a mixture of potassium carbonate and potassium hydroxide [47] and then irradiated in an open vessel in a domestic MW oven for 55-150 s (Eq. 32). 

Jasminaldehyde can be obtained classically from heptanal and benzaldehyde in 70% yield within 3 days at room temperature (Eq. 49). By use of a 600-W domestic MW oven, however, an enhanced yield of 82% was achieved in only 1 min. The amount of side-products (self condensation of n-heptanal) decreased from 30 to 18% when this technique was used [73]. a-Hexylcinnamic aldehyde and chalcone have been synthesized, by the same method, from octanal and acetophenone, respectively [74]. 

The conversion of aryl iodides to aryl phosphonates, useful precursors to aryl phos-phonic acids, has been conducted in a Teflon autoclave by Villemin and colleagues [132]. A domestic MW oven was used for these experiments and the reaction times using classic heating were effectively reduced from 10 h to 4-22 min. The reactiv-... 

Different research groups have shown that this class of compound can be efficiently synthesized, with high yields and short reaction times, by using MW irradiation [31]. For example, Loupy et al. [31a] obtained unsymmetrical DHPs (1 and 2, Scheme 17.4) by reaction (in a one-pot procedure) of an aldehyde, a 1,3 diketone (or a yS-ketoester), and methyl j8-aminocrotonate. By using a solid inorganic support under solvent-free conditions in a domestic MW oven the desired products... 

N-substituted 1,4-dihydropyridines 14 without substituents on the 2 and 6 positions have broad pharmaceutical activity. For example, these species have been reported to be novel potential inhibitors of HIV-1 protease and are of interest for their anticancer activity [39, 40]. Compounds 14 can be prepared, in yields of 62-94%, by one-pot condensation of an aromatic aldehyde, 2 equiv. ethyl propiolate, and an amine, under solvent-free conditions, in a domestic MW oven (Scheme 17.10) [41]. 

The reaction was conducted under solvent-free conditions in a domestic MW oven using four different kinds of solid support (silica gel, acidic alumina, mont-morillonite K-10, and zeolite HY). The best results (77-94%) were obtained with silica gel and an optimized irradiation time of 2 min. In the absence of a solid support, under neat conditions, the products were obtained in low yields and the results were not reproducible. 

The reaction mixture was irradiated in a domestic MW oven for 5 min on a surface of bentonite clay. Not only traditional j8-keto esters, but also, for example, cyclic 1,3-diketones can participate in this MCR, thus enabling a four-component Hantzsch-type synthesis of unsymmetrically substituted 1,4-pyridines 20 (Scheme 17.15) [29, 37]. 

The reaction occurs on the surface of montmorillonite clay impregnated with catalytic amount of CuBr under solvent-free conditions. By irradiation for 3.5 min in a domestic MW oven the desired 21 are synthesized in 70-92% yield. The same reaction took around 4 h under traditional thermal conditions (80 °C, oil bath) to afford the expected quinoline derivatives 21 in only moderate yield (max. 64%). 

Significant rate and yield enhancements have been reported for Biginelli reactions performed under MW irradiation conditions. Most of these procedures are solvent-free and were performed in a domestic MW oven and require various catalysts such as polyphosphate ester (PPE) [59], Cu(II) salts [60], iodine-alumina [61], montmorillonite KSF clay [62, 63], or different chlorine-containing catalytic systems [64],... 

Poly(ethylene glycol) (PEG) is linked to acetoacetate by reaction of PEG with 2,2,6-trimethyl-41-f-l,l-dioxin-4-one 27 in anhydrous toluene under reflux for 5 h. The DHPMs synthesis was achieved by mixing the PEG-linked acetoacetate, urea, and the corresponding aldehyde in the ratio 1 2 2 with a catalytic amount of nonoxidant polyphosphoric acid (PPA) [59]. This mixture was irradiated in a domestic MW oven for 1.5 to 2.5 min to obtain 28 in 70-94% yield. 

Unlike the classical Biginelli reaction, which only tolerates open-chain jS-keto esters, cyclic j5-diketones can also participate in a related MGR [66], This procedure requires Meldrum s acid 29a (X = O and Z = CMc2) or barbituric acid derivatives 29b (X = NH or NMe and Z = GO), urea, and aldehydes (Scheme 17.21). The mixture was irradiated in a domestic MW oven for 4 min under solvent-free conditions. The reaction requires a Bronstedt acid as catalyst to give, selectively, a family of novel heterobicyclic compounds 30 in good yields (70-83%). 

This reaction was performed in a domestic MW oven for 9-15 min at a power level of 480 W. The yields were good (76-88%) and triazines 44 were obtained with high diastereoselectivity in favor of the cis isomers (>96 4). This ratio is much higher than that from a comparable experiment in which the reaction was performed under traditional heating conditions. With the same reaction times and temperature (90 °C, measured directly after irradiation) product yields were significantly lower (19-31%) and diastereoselectivity (>56 44) was much lower. 

The reaction was performed in an unmodified domestic MW oven with an irradiation time of 10-14 min at 560 W and furnished good yields (73-86%) of the final product 58. Diastereoselectivity strongly favored the syn isomers (>96 4). 

Although Ugi reactions can proceed rapidly, reaction times from one to several days are not uncommon. MW conditions could speed up these reactions. Thus, after attachment of poly(ethylene glycol) (PEG)-grafted polystyrene to an amino-functionalized building block, the Ugi reaction has been performed in a domestic MW oven, using a mixture of DCM and MeOH (2 1), with a total irradiation time of 5 min. After cleavage from the resin by treatment with TFA DCM (19 1) for 1 h the desired bisamides 66 were obtained in up to 96% yield. This reduced reaction times by at least a factor of ten compared with conventional reaction conditions. 

The Wittig olefination, a widely used transformation for the construchon of carbon-carbon double bonds, has been improved. Some difficult reacbons of stable phosphorus ylides with ketones in the absence of solvent are accelerated by MW irradiation using a domestic MW oven and the procedure affords improved yields compared with reactions carried out by conventional heating methods (Scheme... 

Although the separation employs an organic solvent to obtain pure olefin, it is still a useful protocol in the total synthesis. Similarly, several phosphonium salts, stabilized as well as non-stabilized, have been prepared in a domestic MW oven [51]... 

For example, Yu et al. showed that polystyrene-bound peptides could be hydrolyzed in 7 min in a domestic MW oven, a process normally taking 24 h. Furthermore, traditional soHd-phase peptide couplings were achieved in 4 min in 99-100% conversion with no detected racemization. A broad range of solid-phase reactions was found to undergo substantial rate acceleration, including Claisen and Knoeve-nagel condensations, nucleophilic substitutions, sucdnimide and hydantoin formation, and Suzuki coupHngs. 

Recently this approach has been extended to parallel combinatorial library synthesis. One example is the solvent-free synthesis of a 96-member library of substituted pyridines via a one-step Hantzsch-3CC conducted in 96-weU micro titer filter plates (Scheme 2.3-12). Here the p-ketoester and aldehyde reagents were impregnated onto a 5 1 bentonite clay-ammonium nitrate mixture. Irradiation for 5 min in a domestic MW oven, followed by washing the product off the support into a receiver daughter plate gave substituted-pyridine products in >70% purity overall. 

Several methyl aryl ketones reacted with sulfur and morpholine (469) under sol-vent-free conditions in a domestic MW oven for 3.5 6 min to give thiomorpholides... 

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