Microwave assisted procedures

One frequently used method for synthesizing 2-quinolones is to react anilines with malonic esters. This reaction can be difficult to accomphsh by conventional methods [48,49] since high temperatures (250-350 °C) are required for the generation of an o -oxoketene intermediate 12 (Fig. 6). In a recent example of this type of reaction, Stadler et al. synthesized 4-hydroxyquinolin-2(lH)-ones by using a microwave-assisted procedure (Scheme 5) [50]. 

As discussed in Section 7.1.4, polymer-bound acetoacetates can be used as precursors for the solid-phase synthesis of enones [33], For these Knoevenagel condensations, the crucial step is to initiate enolization of the CH acidic component. In general, enolization can be initiated with a variety of catalysts (for example, piperidine, piperidinium acetate, ethylenediamine diacetate), but for the microwave-assisted procedure piperidinium acetate was found to be the catalyst of choice, provided that the temperature was kept below 130 °C. At higher reaction temperatures, there is significant cleavage of material from the resin. 

Several microwave-assisted procedures have been described for soluble polymer-supported syntheses. Polyethylene glycol) (PEG)-supported aryl bromides have been shown to undergo rapid palladium(0)-catalyzed Suzuki couplings with aryl boronic acids in water (Scheme 12.16) [63], The reaction proceeded without organic cosolvent... 

For example, it was reported in several independent articles that multicomponent treatment of 5-amino-3-methylpyrazles with 1,3-cyclohexandiones and aldehydes under refluxing in EtOH [82, 83], in DMF with methanol [84], or with application of continuous-flow microwave-assisted procedure in DMSO [85] yielded exclusively pyrazoloquinolinones 50 (Scheme 23). On the other hand, the treatment of 3-unsub-stituted 5-aminopyrazoles with cyclic p-diketones or ketosulfones gave mixtures of Hantzsch dihydropyridines 51 and Biginelly dihydropyrimidines 52 in different ratios [86]. 

The iodination of pyrimidines requires the presence of an activating substituent, and is normally performed with reagents such as A -iodosuccinimide (NI8) or iodine monochloride (ICl). A microwave-assisted procedure for the rapid and high-yielding C-5 iodination of substituted pyrimidinones and pyrimidine nucleosides with NIS in dimethylfor-mamide (DMF) has been developed, and thus the iodination of uracil occurred in 98% yield with just 3 min reaction time <200381039>. 

Direct electrophilic alkylation in the pyrimidine 5-position can be carried out on pyrimidines with at least two strongly donating groups, more readily with three such groups. For example, uracil can be 5-hydroxymethylated by formaldehyde under alkaline conditions, and a microwave-assisted procedure has now been developed which allows formation of 5-hydroxymethyluracil in 98% yield, with just 3 min of reaction time <2002SL2043>. 

Microwave-assisted procedures have also been developed for the condensation of substituted amidines and ureas with malonic acid derivatives <2005TL5727, 2007AJC120>. For example, reaction of substituted ureas 668 with malonic acid 667 in the presence of acetic anhydride gave 1,3-disubstituted barbituric acids 669, while similar condensation with cyanoacetic acid 670 gave 6-aminouracil derivatives 671 <2005TL5727>. 

The Biginelli procedure is amenable to microwave technology, and several microwave-assisted procedures have now been published <2002SC147, 2004SL235>. An example is the microwave-assisted solution-phase synthesis of dihydropyrimidine C-5 amides and esters 723 using ytterbium triflate as the Lewis acid catalyst <2006T4651>. 

Substituted 4-aminoquinazolines 847 can be prepared by combining 2-aminobenzonitriles 846 with nitriles under basic conditions <2000JME2227, 2005SC2481>, and a microwave-assisted procedure is now available that enables these compounds to be produced very efficiently <2000TL2215>. 

A common method for the preparation of 2(177),4(3//)-quinazolinediones consists of the fusion of anthranilic acid derivatives 853 with urea, and a microwave-assisted procedure has now been developed that produces the quinazo-linediones 854 in excellent yields <2005CL1438>. 

To accelerate the reactions rates and to increase their yields, sometimes microwave-assisted procedures are applied. The first mention of using a solvent-free microwave procedure was in [55]. The authors described the synthesis of 1,3,5-triarylpyrazoline by the cyclization of chalcones with phenylhydrazine on a basic alumina solid support. The target heterocycles were synthesized under microwave irradiation in high yields (up to 85%) in 1-2 min instead of 3 h in the case of thermal activation. Another publication [56] deals with the rapid (2-12 min) solvent-phase cyclization of naphthyl-substituted chalcones 41 and hydrazines 42 in a microwave field yielding the appropriate pyrazolines 43 quantitatively (Scheme 2.10). 

Barra et al. [40] have described a microwave-assisted procedure based on atomic fluorescence for the quantitative determination of down to 0.006 xg/g of inorganic arsenic in soils. 

Frolov et al. [19] reported the formation of oxazole ring (vi) by the reaction of 5-amino-4-hydroxy-3(2H)-pyridazinone with various carboxylic derivatives using a microwave assisted procedure. 

Recently, a microwave-assisted procedure attaining > 300 °C was also reported for complete decomposition with a new system, the UltraCLAVE 2 (Goessler and Pavkov 2003). 

Significant rate accelerations and higher loadings are observed when the microwave-assisted procedure was compared with the conventional thermal procedure. Reactions times were reduced from 12 to 48 h with conventional heating at 80 °C to 5-15 min with MW flash heating in NMP at temperatures up to 200 °C. Finally, careful kinetic comparison studies have shown that the observed rate enhancements can be attributed to the rapid direct heating of the solvent (NMP) rather than to a specific nonthermal microwave effect [35]. 

N-alkylation of 2-halopyridines A microwave-assisted procedure (focused waves) for N-alkylation of 2-halopyridines has been described the noticeable microwave effect was indicative of a polar TS [135] (Eq. 49) ... 

The development of a cost-effective microwave-assisted procedure for synthesis of pyrido fused-ring systems, by applying the tert-amino effect, has been described by Van der Eycken and coworkers (Scheme 10.62) [126]. 

A one-pot synthesis of N-substituted 4-aryl-l, 4-dihydropyridines using a microwave-assisted procedure was described in 2001 (Scheme 10.97) [187]. Among a variety of solid supports (Kio, acidic alumina, zeolite HY, silica gel), silica gel was proved to be the most efficient. After irradiation for 4 min, the reactions led to yields ranging from 62 to 94%. 

Pieters et al. [78] described straightforward microwave-assisted procedures for rapid preparation of azido carbohydrates 109 which were applied in a general microwave-enhanced regioselective Cu -catalyzed [3+2] cydoaddition readion with different... 

It has been shown that application of previously synthesized ethers of isosorbide was beneficial and enabled the preparation of polyethers in better yields than the polyethers obtained in direct reactions of isosorbide and dibromo or dimesyl alkanes [47, 48]. Moreover, the molecular weights of the polyethers were higher than of those prepared in the earlier work [47] and the molecular weight distributions of new polyethers were similar or lower. Such a microwave-assisted procedure can contribute to the synthesis of alternating polyethers and further modification of their properties. 

Approximately 2500 publications on microwave activation in organic synthesis have appeared in the literature. The spectacular growth of this technique is undoubtedly connected with the development of new, adapted, reactors enabling accurate control and reproducibility of the microwave-assisted procedures but also to the increasing involvement of industrial and pharmaceutical laboratories. This interest has been also been manifested by several reviews and books in the field including, very recently, the Wiley-VGH book by Oliver Kappe and Alexander Stadler... 

Cossy and co-workers developed a rapid convergent microwave-assisted procedure for the synthesis of benzoannulated spiroacetals based on a... 

Inorganic analysis with ICP-MS has also been used to discriminate between groups of papers, altiiough the techniques were destructive. In one case, the elements Na, Mg, Al, Mn, Sr, Y, Ba, La, and Ce were foimd sufficient for classification and discrimination. Paper samples were treated in hydrogen peroxide and nitric add solution and were digested via a microwave-assisted procedure dear discrimination of two origins for paper exhibits was demonstrated. The results are summarized in Figures 14.1 and 14.2. 

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