Microwave irradiation, advantages

In recent years, parallel to the emergence of SPOS, microwave-mediated organic synthesis has come to hght and has developed into a popular field [24-31]. The main advantage of microwave dielectric heating compared to other conventional methods, such as hot plate, oil bath or isomantle, is the tremendous rate enhancement generally observed under microwave irradiation conditions. Various theories have been proposed to explain the source of the rapidity of microwave chemistry [32,33]. However, the gener-... 

Soluble polymers have also been used as support. These exploit the combined advantage of homogeneous with those of soHd-phase chemistry [36]. PEG linked 5-bromothiophene-2-carboxyUc acid was cross-coupled with several arylboronic acids under microwave irradiation (constant power of 75 W) using water as the solvent (Scheme 17). Interestingly, microwave irradiation gave less ester cleavage than classical heating (70 °C). The polymeric support remained stable under both conditions. 

In 1996, the first examples of intermolecular microwave-assisted Heck reactions were published [85]. Among these, the successful coupling of iodoben-zene with 2,3-dihydrofuran in only 6 min was reported (Scheme 75). Interestingly, thermal heating procedures (125-150 °C) resulted in the formation of complex product mixtures affording less than 20% of the expected 2-phenyl-2,3-dihydrofuran. The authors hypothesize that this difference is the result of well-known advantages of microwave irradiation, e.g., elimination of wall effects and low thermal gradients in the reaction mixture. 

Scheme 6.93) [192]. Using either of the two solvent systems, all studied cycloaddition reactions were completed in less than 1 min upon microwave irradiation at 50 °C employing 3 mol% of the catalyst. An additional advantage of using the ionic liquid l-butyl-3-methylimidazolium hexafluorophosphate (bmimPF6) as solvent is that it facilitates catalyst recycling. 

Most of these publications describe important accelerations of a wide range of organic reactions especially when performed under solvent-free conditions. The combination of solvent-free reaction conditions and microwave irradiation leads to large reductions in reaction times, enhancement of yield, and, sometimes [3, 4] in selectivity with several advantages of an eco-friendly approach, termed green chemistry . 

The V20s/Si02 catalyst for o-xylene oxidation prepared by wet impregnation under microwave irradiation had several advantages [6] compared with that prepared by the conventional thermal method ... 

Heating by means of single-mode microwave irradiation enables readily adjustable and controlled bulk heating which can be performed safely and with very low energy consumption. The synthetic chemist of today can take advantage of the unique carbon-carbon bond formation reactions afforded by organometallic chemistry and make the reaction happen in seconds or minutes, an important feat, because many transition-metal-catalyzed reactions are time-consuming. 

Despite the many simple methods for preparation of carboxylic esters and thioesters, in some instances, use of 1-acylbenzotriazoles 915 as O and S acylating agents may be advantageous. For example, easy to prepare salicylic acid derivative 941 reacts with cyclopentanol under microwave irradiation to give 92% yield of cyclopentyl salicylate in 10 min <2006JOC3364>. In another example, L-phenylalanine derivative 942 reacts with benzyl mercaptan... 

The application of phase-transfer catalysis to the Williamson synthesis of ethers has been exploited widely and is far superior to any classical method for the synthesis of aliphatic ethers. Probably the first example of the use of a quaternary ammonium salt to promote a nucleophilic substitution reaction is the formation of a benzyl ether using a stoichiometric amount of tetraethylammonium hydroxide [1]. Starks mentions the potential value of the quaternary ammonium catalyst for Williamson synthesis of ethers [2] and its versatility in the synthesis of methyl ethers and other alkyl ethers was soon established [3-5]. The procedure has considerable advantages over the classical Williamson synthesis both in reaction time and yields and is certainly more convenient than the use of diazomethane for the preparation of methyl ethers. Under liquidrliquid two-phase conditions, tertiary and secondary alcohols react less readily than do primary alcohols, and secondary alkyl halides tend to be ineffective. However, reactions which one might expect to be sterically inhibited are successful under phase-transfer catalytic conditions [e.g. 6]. Microwave irradiation and solidrliquid phase-transfer catalytic conditions reduce reaction times considerably [7]. 

The Pd-catalyzed carbonylation of o-vinylaryl bromides using Mo(CO)6 as CO source with microwave irradiation gave indanone 338 and 3-acylaminoindanone 340, which are key intermediates for the synthesis of inhibitors of human immunodeficiency virus type 1 (HIV-1) protease and Plasmepsin I and II (Scheme 46). These polycyclic compounds were obtained in less than 30 min in high yields. The results clearly indicate the power and advantage of this protocol, especially for the combinatorial parallel synthesis of a library of compounds. 

The Sonogashira coupling of halopyridines was also achieved by other means. Resin bound bromopyridine derivatives, for example, underwent smooth coupling with acetylenes as well as with arylboronic acids and aryltin reagents.44 The advantageous effect of microwave irradiation on the coupling of halopyridines and trimethylsilylacetylene was also reported.45... 

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