Microwave-assisted methods, for

Scheme 15 Other microwave-assisted methods for the synthesis of imidazoles...

Scheme 22 Improved microwave-assisted method for the synthesis of 1,2,4-triazines...

In the context of preparing potential inhibitors of dihydrofolate reductase (DHFR), the group of Organ has developed a rapid microwave-assisted method for the preparation of biguanide libraries (Scheme 6.174) [330]. Initial optimization work was centered around the acid-catalyzed addition of amines to dicyandiamide. It was discovered that 150 °C was the optimum temperature for reaction rate and product recovery, as heating beyond this point led to decomposition. While the use of hydrochloric acid as catalyst led to varying yields of product, evaluation of trimethylsilyl chloride in acetonitrile as solvent led to improved results. As compared to the protic... 

The development in microwave chemistry has been remarkable during the last few years from the first reports in which, typically, domestic ovens were used to modern applications with state-of-the-art single-mode cavities. We believe that it is today possible today to develop robust microwave-assisted methods for nearly any reaction that needs an external heat source and we have proved it is possible to perform transition-metal catalyzed reactions very cleanly and selectively. 

Benzylic Bromination of Aromatic Compounds. An efficient and fast microwave-assisted method for the preparation of benzylic bromides has appeared The 2-trimethylsilylethyl substituent on the benzenoid ring of 3 undergoes benzylic bromination followed by elimination of MesSiBr and addition of bromine to produce the dibromo compound (4) (eq 31). The ketone (5) is also observed from the hydrolysis of (4). ... 

Upadhyay and Jursic (2011) have proposed an efficient, safe, high yielding and rapid microwave-assisted method for the preparation of protected p-bromomethyl and p-dibromomethylanilines, which act as new protection groups for alcohol, thiol, and amine. This method involves microwave-assisted N-bromosuccinimide (NBS) radical bromination of readily available N-protected p-toluidine. It was observed that the microwave-assisted radical bromination was superior to the conventional NBS radical bromination. 

When a similar transformation was attempted using a dialkylether in place of an aryl alkyl ether, yields obtained were much lower. An alternative microwave-assisted method for promoting esterification uses phase transfer catalysis. Irradiation of potassium acetate with alkyl halides for 1-2 min (Aliquat 336, 5-10%) gives the product in good to excellent yields (> 92%) (Bram et al., 1990). 

The use of microwave irradiation for this reaction, compared to conventional thermal heating, was investigated. Chloroform used as solvent under the conventional heating did only allow a temperature of 60 °C and a direct comparison between the two methods is therefore somewhat unfair imder these circumstances. Nevertheless, the microwave-assisted method is attractive and proved useful for both primary and secondary amines resulting in highly substituted pyrazolo ring-fused pyridones 40 in 68-86% yields within only 10 min. 

As microwave sample preparation has evolved, standard microwave procedures have been developed and approved by numerous standard methods organisations (ASTM, AOAC International, EPA, etc.), see ref. [64]. Examples are standard test methods for carbon black/ash content (ASTM Method D 1506-97), lead analysis in direct paint samples (ASTM Method E 1645-94), etc. Table 8.15 shows some microwave ashing references (detection weight). A French AFNOR method utilises the atmospheric pressure single-mode microwave method as an alternative sample preparation procedure for Kjeldahl nitrogen determination [84], The performance of a microwave-assisted decomposition for rapid determination of glass fibre content in plastics for QC has been described [85]. 

Microwave irradiation greatly improved the reaction between the lactim ethers 157 and anthranilic acid, as regards yields, reaction time and also the integrity of the stereocenter, as shown by the results obtained for compounds 158 (R1 = (R)-Me R4 = H R2 = Me, 4-MeO-Bn, (CH2)2Ph, 2-naphthylmethyl) and 158 (R =(R)-Me R4 = Me R2 = indol-3-ylmethyl), prepared by both the conventional thermal and the microwave-assisted methods <2004SL803>. 

Recently, the synthesis and evaluation of a new pyrazinone class of tryptase inhibitors has been reported. One step in the preparation of these compounds involved regioselective chloride displacements from a dichloropyrazinone scaffold using amines and anilines as nucleophiles. The aniline reactions required the use of microwave-assisted heating for 12 min at 120 °C, as illustrated in Scheme 23 [84]. Although the aniline-derived compounds (e.g., 50) were modest inhibitors, other compounds from this study, synthesized by classical heating methods, were shown to be highly potent tryptase inhibitors. 

A study was carried out for LEE by the Soxhlet method and microwave-assisted extraction for the determination of the priority phenols in soil samples. Recoveries varied from 67 to 97% with RSD between 8 and 14% for LEE, and >70% for the MAP, except for nitrophenols that underwent degradation when the latter method was applied. LOD was from 20 ngg for 2,4-dimethylphenol to 100 ngg for pentachlorophenol. The best detection method for EC was atmospheric pressnre chemical ionization MS (APCI-MS). The most abnndant ions obtained by this detection method were [M — H] for the lowly chlorinated phenols and [M — H — HCl] for tri-, tetra- and pentachlorophenols . 

Recently, 2-alkyl- and 2-aryl-substituted benzimidazole derivatives 15 have been synthesized from 1,2-diaminobenzene dihydrochloride 13 and its corresponding acids 14 in the presence of polyphosphoric acid using microwave-assisted methods (Scheme 3). The reaction time required for the synthesis of benzimidazole derivatives 15 was reduced to minutes by this method compared to conventional synthesis, which required up to four hours of heating to complete the reaction. Furthermore, it was found that the application of microwave irradiation increased yields by 10-50% (Table 1). It has been... 

Negishi cross-coupling was used for synthesis of pyridylpyrimidines using classical thermal or microwave-assisted conditions [66]. Distribution and yield of desired compounds and possible by-products proved to be very dependent on the type of energy input. In contrast with thermal conditions, the microwave-assisted method enabled efficient access to dicoupled compounds (Scheme 10.30). 

A comparison of mechanosynthesis with other synthetic methods showed the superiority of microwave-assisted method and solution conditions over mechanoehemical and ultrasound reactions for the less-reactive carbodiimides. More-reactive carbodi-imides provide full conversion under aU conditions, while best yields were obtained in MW and solution reactions (entries 6 and 7). 

Nucleophilic aromatic substitution reactions were employed to place amines on pyrimidine and pyrimidinone rings. As a more economical substitute for Buchwald-Hartwig cross-coupling reaction conditions GeUis and collaborators developed a DMAP-catalyzed, microwave-assisted method to form 4-hetero-arylamino-substituted quinazolines (Scheme 33) (14T8257). Treatment of... 

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