The microwave approach

Once again the scientist chose to use the SNAr reaction to gain access to the key o-nitroaniline intermediate however, it is quite apparent from Table 8.7 that the use of microwave synthesis resulted in rapid optimization of this key reaction and significantly improved yields. The use of w-butanol as solvent for this substitution reaction gave high yields (88%) in only 15 min. It should also be pointed out that while in the thermal example DMSO was the optimal solvent, in the microwave example this solvent resulted in decomposed starting materials. 

The second step was also similar to the thermal method. The scientist chose to reduce the nitro group by transfer hydrogenation. While this reaction resulted in poor yields and mostly uncyclized materials in the thermal approach, in the microwave example the yields were typically high with the desired cyclized intermediate predominating in the reaction mixture (see Table 8.8). 

While the scientist in the nonmicrowave approach had concluded that this library could not be generated using his synthetic strategy, the microwave approach had shown the ability to rapidly optimize the reaction conditions to produce the final product. It should also be highlighted that while the thermal approach required 37 working days 

Solvent Equiv. AA Base (equiv) Time (min) Temp (°C) Yield (%) 

This example is unique in that the two groups were unaware of what methods and techniques were applied and since both groups had no previous knowledge of the methods of generating this scaffold, it provides a unique insight into the timesavings directly associated with microwave-assisted synthesis in library development and optimization. 

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The reaction of silyl ketone acetals with imines under irradiation has been explored. The versatility of the microwave approach is illustrated in Scheme 8.45. 

The reaction of C60 with o-quinonemethide, prepared from o-hydroxybenzyl alcohol (110) (Scheme 9.32), was performed in a modified domestic oven at 800 W and gave 111 in 27% yield after only 4 min [72], Although Eguchi et al. [83] reported the same reaction with a slightly better yield (31%) by thermolysis in a sealed vessel, the microwave approach to this adduct has the advantage of simplicity, and avoids the risks associated with high-pressure conditions. 

The microwave approach has been developed by Owen (1972), Goumay (1979) and Thompson (1981). Although Thompson (1981) has stated that "conclusive proof does... 

The reaction of silyl ketone acetals with imines under the action of irradiation has been explored. The versatility of the microwave approach is illustrated in Scheme 10.66 [130]. When the reactions were performed by adsorption of the reagents on to Kio montmorillonite clay, the aminoester is formed. Conversely, when the reaction was performed by mixing the neat reagents with KF and 18-crown-6 and irradiation in a closed vessel, /i-lactams were isolated in moderate to good yields. 

The microwave approach has been used for parallel synthesis of an 880-member library in 96 well plates ten different amino acids, each bearing a different acyl group, were coupled to the 4-sulfambutyryl resin and 88 different amines were used in the cleavage step. 

Titanium(IV) and zirconium(IV) complexes of the types Cp2MCl(HPO), Cp2M(HPO)2, Cp2M(0-N-0), and Cp2M(0-N-S) have been prepared by reaction of titanocene dichloride or zirconocene dichloride with the appropriate ligand using THF as the solvent (Scheme 7.18). The reactions are complete in 4-7 min as opposed to 14-18 h conventionally. Yields were always higher for the microwave approach (YIF = 1.1-1.2). 

Many reports have focused on the functionalization and derivatization of cyclo-pentadienyl groups bound to iron in ferrocene complexes. As an example, a series of ferrocenyl esters have been prepared via solvent-free reactions of ferrocenoyl fluoride with substituted phenols after microwave heating for just 1 min. " In the case of 4-bromophenol, the YIF was 1.2, but most substrates gave somewhat lower yields than the conventional method. However, the microwave approach did not require the addition of A, A -dimethylaminopyridine that was necessary conventionally. Other reports include a green approach to the acylation of ferrocene using the polymeric sulfonic acid Nation as an acid catalyst " and a one-pot approach to the synthesis of l,5-dioxo-3-substituted[5]ferrocenophanes from l,T-diacetylferrocene and aldehydes via a Claisen-Schmidt reaction. " " ... 

PDI =1.16) prepared in just 1 min (56% conversion) under microwave conditions was employed as a macroCTA for the polymerization of NIPAM ([NIPAM]/[PDMA macroCTA]/ [AIBN] = [100]/[l]/[0.05]), 71% conversion was obtained in 30 min, resulting in a polymer with A n= l SOOgmol" (PDI = 1.17) (Figure 17(a)). Similarly, PNIPAM macroCTAs prepared by the microwave approach were also successfully utilized to copolymerize DMA. For instance, a PNIPAM homopolymer (Mn = 7000gmol" PDI=1.18) prepared in just 12 min (68% conversion) under microwave conditions was... 

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