Resin microwave-assisted

Fig. 5 Microwave-assisted loading protocol of carboxylic acids to chlorinated polystyrene Wang resin...

Fig. 7 Kinetics of microwave-assisted loading of 2-chlorotrityl chloride resin with Fmoc-isoleucine at 110 °C. For comparison, the dashed line indicates the level of loading after 1 h at room temperature...

Investigation of the microwave-assisted attachment of Fmoc-protected amino acids onto 2-chlorotrityl chloride resin indicated higher loadings and increased rates compared to standard room temperature procedures [146]. In this comparative study standard procedures yielded 0.37 mmol/g loading after 1 hour, whereas at 110 °C using microwave dielectric heating, a similar result (0.38 mmol/g) was obtained after only 15 min (Fig. 7). 

A constant interest in the development of new rapid methodologies for the preparation of oxazole hbraries is motivated by their presence in numerous biologically active natural products. Janda and coworkers were hrst to show that oxazoles can be obtained by microwave-assisted treatment of polymer-bound a-acylamino-/f-ketoesters with Burgess reagent [68]. Hydroxybutyl-functionalized /anda/el resin was used for this investigation, with key steps being monitored by on-bead FT-IR. First, a resin-bound acetoacetate was pre-... 

Fig. 15 Microwave-assisted isoxazole synthesis via on resin [3-1-2] cycioaddition. Reagents and conditions a 1-nitrobutane, DMTMM, DMAP, MeCN, THE, MW 80 °C, 5 min, open vessel b TEA CH2CI2 (5 95), rt, 20 min...

Fig. 39 Microwave-assisted synthesis of pyridinones from resin-bonnd 2(iH)-pyrazinones. Reagents and conditions a dimethyl acetylenedicarboxylate, chlorobenzene, reflux (132 °C), 1-2 days or 1,2-dichlorobenzene, MW 220 °C, 20-40min b bromobenzene, reflux (156 °C), 2h or 1,2-dichlorobenzene, MW 220 °C, 10min R = OC2H4C2H c TFA, reflux (72 °C), 20-24 h or TFA/Ch2Cl2, MW 120 °C, 10-40min. R=OMe or Ph, R = methoxyphenyl. All microwave-assisted reactions were rim in sealed vessels...

As for the solid support, several polymer-supported amines were tested (Fig. 2). For either the pyrazole and isoxazole synthesis, the best results were given by aniline-functionalized cellulose, which has also the advantage of a relatively low cost. For the 2-aminopyrimidine library, polystyrene-based piperazine and piperidine gave products with a much higher purity compared with other secondary non-cyclic or primary amines, hi both cases, the resins could be reused for up to four times before degradation in their behavior was observed. This reusability could be further enhanced (up to 10 cycles for cellulose-based aniline) when the microwave-assisted protocols were used. 

The first microwave-assisted Suzuki reactions involving heteroaromatic skeletons were reported in 1996 [35]. Hallberg et al. Hnked the substrates 4-iodo and 4-bromobenzoic acid to a TentaGel-Rink resin (Scheme 16). Suzuki reactions on these soUd-phase-Unked substrates were easily performed in less than 4 min using a constant microwave irradiation power (45 W) (no temperature control Standard acidic cleavage with TEA yielded the corresponding biaryls with an excellent yield. 

AT-acetyltryptamines could be obtained via microwave-assisted transition-metal-catalyzed reactions on resin bound 3-[2-(acetylamino)ethyl]-2-iodo-lH-indole-5-carboxamide. While acceptable reaction conditions for the application of microwave irradiation have been identified for Stille heteroaryla-tion reactions, the related Suzuki protocol on the same substrate gave poor results, since at a constant power of 60 W, no full conversion (50-60%) of resin-bound 3-[2-(acetylamino)ethyl]-2-iodo-lH-indole-5-carboxamide could be obtained even when two consecutive cross-coupling reaction cycles (involving complete removal of reagents and by-products by washing off the resin) were used (Scheme 36). Also under conventional heating at 110 °C, and otherwise identical conditions, the Suzuki reactions proved to be difficult since two cross-coupling reaction cycles of 24 h had to be used to achieve full conversion. 

Applications The broad industrial analytical applicability of microwave heating was mentioned before (see Section 3.4.4.2). The chemical industry requires extractions of additives (antioxidants, colorants, and slip agents) from plastic resins or vulcanised products. So far there have been relatively few publications on microwave-assisted solvent extraction from polymers (Table 3.5). As may be seen from Tables 3.27 and 3.28, most MAE work has concerned polyolefins. 

The preparation of resin-bound nitroalkenes via a microwave-assisted Knoevenagel reaction of resin-bound nitroacetic acid with aryl and alkyl substituted aldehydes is reported. The potential of these resin-bound nitroalkenes for application in combinatorial chemistry is demonstrated by a Diels-Alder reaction with 2,3-dimethylbutadiene (Scheme 8.9). It is also used for one-pot three-component tandem [4+2]/[3+2] reactions with ethyl vinyl ether and styrene 46... 

As far as polymer supports for microwave-assisted SPOS are concerned, the use of cross-linked macroporous or microporous polystyrene (PS) resins has been most prevalent. In contrast to common belief, which states that the use of polystyrene resins limits reaction conditions to temperatures below 130 °C [14], it has been shown that these resins can withstand microwave irradiation for short periods of time, such as 20-30 min, even at 200 °C in solvents such as l-methyl-2-pyrrolidone or 1,2-dichlorobenzene [15]. Standard polystyrene Merrifield resin shows thermal stability up to 220 °C without any degradation of the macromolecular structure of the polymer backbone, which allows reactions to be performed even at significantly elevated temperatures. 

An interesting approach to resin functionalization has been presented by the group of Yaylayan, who described microwave-assisted PEGylation of Merrifield... 

Combs and coworkers have presented a study on the solid-phase synthesis of oxa-zolidinone antimicrobials by microwave-mediated Suzuki coupling [38], A valuable oxazolidinone scaffold was coupled to Bal resin (PS-PEG resin with a 4-formyl-3,5-dimethoxyphenoxy linker) to afford the corresponding resin-bound secondary amine (Scheme 7.18). After subsequent acylation, the resulting intermediate was transformed to the corresponding biaryl compound by microwave-assisted Suzuki coupling. Cleavage with trifluoroacetic acid/dichloromethane yielded the desired target structures. 

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