Reactions with microwaves

Carbonylation reactions with microwave irradiation have been investigated in connection with solid-state combinatorial chemistry.Since reactions requiring gaseous reagents cannot use microwave irradiation, metal carbonyl complexes, such as Mo(CO)6, Cr(CO)6, W(CO)6, and Co2(CO)8 have been employed as source of carbon monoxide. " Examples of aminocarbonylation performed with microwave irradiation are presented in Section 11.15.4.3 (vide supra). 

FIGURE 12.25. Diels-Alder reaction with microwave radiation. (Source Niicher, 2004). 

In this section, typical and recent examples of the coupling of solvent-free reactions with microwave activation will be described. Comparisons with con-... 

Synthesis of 2-thioxotetrahydropyrimidin-4-(lH)-ones Libraries of 2-thioxotetrahy-dropyrimidin-4-(lH)-ones can be prepared by multicomponent reaction of amine, isothiocyanate, and yS-dielectrophile components (Scheme 7.23). [PEG -RMIM]X ionic liquids have been used in this reaction with microwave irradiation (Scheme 7.24) [75]. In a step-by-step approach, treatment of [PEG -RMIM]X with acryloyl chloride provided a supported acryloyl ionic liquid phase which was reacted with an amine and then isothiocyanate to give a thiourea. Cyclization-cleavage from the ionic liquid support to give the desired 2-thioxotetrahydropyrimidin-4-(lH)-one was achieved by using low-power microwaves at 120 °C for 15-45 min in the presence of diethylamine. 

N-aryl-2-piperazmones are of great interest as famesyl-transferase inhibitors, and both N-aryl-2-piperazinones and N-aryl-2,5-piperazinediones are synthetic precursors of N-arylpiperazines which are key elements in monoamine receptor-active drugs. Lange et al. enhanced the Goldberg reaction with microwaves for synthesis of N-arylpiperazinones, N-arylpiperazinediones, and N-aryl-3,4-dihydroquinolines [88]. Microwave irradiation greatly accelerates the reaction when NMP is used as solvent. 

Coumarins are important compounds with applications as pharmaceuticals and agrochemicals. Some 7-aminocoumarin-4-carboxylates have been synthesized by use of the Pechmann reaction, with microwave irradiation of the reactants on solid supports (graphite-Kio) (Scheme 10.105) [206]. The synthesis of unsubstituted coumarins (C-4 position) has also been reported [207]. 

Another technique used for intermolecular Diels-Alder (DA) reaction with microwave irradiation takes advantage of the intrinsic properties of the solvent [3jj. In this context, an interesting example is the microwave-induced Diels-... 

Few other qfdoaddition reactions with microwave irradiation have appeared in the literature since the first applications were published. In particular, the [2+2+1] reaction, known as the Pauson-Khand reaction, [6+4], and tandem [6+4]-[4+2] cycloadditions have been reported as being performed successfully under micro-wave conditions. A range of examples is described below. 

Yamane and Ren established an efficient molybdenum-mediated carbamoyla-tion of aryl halides [302, 303]. The procedure is simple and requires only a slight excess of carbon monoxide in the form of Mo(CO)g. This reaction provides a method for the synthesis of a variety of amides. Primary amides are also prepared in the reaction with aqueous ammonia (Scheme 2.48). Roberts and colleagues reported a similar reaction with microwave irradiation. 

Scheme 21.16 Aldol reaction with microwave irradiation at subzero temperatures.

Reactions with microwave heating are more reproducible as compared to conventional heating because of uniform heating and better control process parameters. The temperature of chemical reactions can also be easily monitored. This is of particular relevance in the lead optimization phase of the dmg development process in pharmaceutical companies. 

Mladenovic et al. (2009) reported that 4-hydroxy-chromene-2-oiie derivatives were easily prepared through condensation reactions with microwave heating. All tested compounds are, in principle, very good potential microorganism growth inhibitors, but their structural diversity resulted in great differences in their inhibitory potential. 

Dihydropyrimidines are associated with broad spectrum of biological activities. Excellent results were obtained for the preparation of dihydropyrimidine derivatives by Biginelle reaction with microwave enhancement (Banks, 1999). An increase in yield was observed to 60-90%, while there was a drastic decrease in reaction time for 12-24 h to 5 min. 

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