Solid microwave-enhanced

Recently it has been shown that the microwave-assisted decoration of the 2(lff)-pyrazinone scaffold can allow an easy introduction of different substituents at the C-3 and even to the less reactive C-5 position [29]. Taking full advantage of combinatorial principles, some of these pathways were transferred to microwave-enhanced solid-phase chemistry, opening the way for the generation of many biologically interesting structures [108]. 

In liquid-solid extraction (LSE) the analyte is extracted from the solid by a liquid, which is separated by filtration. Numerous extraction processes, representing various types and levels of energy, have been described steam distillation, simultaneous steam distillation-solvent extraction (SDE), passive hot solvent extraction, forced-flow leaching, (automated) Soxh-let extraction, shake-flask method, mechanically agitated reflux extraction, ultrasound-assisted extraction, y -ray-assisted extraction, microwave-assisted extraction (MAE), microwave-enhanced extraction (Soxwave ), microwave-assisted process (MAP ), gas-phase MAE, enhanced fluidity extraction, hot (subcritical) water extraction, supercritical fluid extraction (SFE), supercritical assisted liquid extraction, pressurised hot water extraction, enhanced solvent extraction (ESE ), solu-tion/precipitation, etc. The most successful systems are described in Sections 3.3.3-3.4.6. Other, less frequently... 

Microwave-assisted extraction (MAE) of analytes from various matrices using organic solvents has been operative since 1986 [128], In this process microwave energy is used to heat solvents in contact with a solid sample uniformly and to partition compounds of analytical interest from the sample matrix into the solvent. The way in which microwaves enhance extraction is not fully understood. The main factors to consider include improved transport properties of molecules, molecular agitation, the heating of solvents above their boiling points and, in some cases, product selectivity. 

Many ionic liquids are based on N,N-dialkylimidazolium cations (BMI) which form salts that exist as liquids at, or below, room temperature. Their properties are also influenced by the nature of the anion e. g. BF T PFg. The C-2(H) in imidazole is fairly labile but the C-4(H) and the C-5(H) are less so. Under microwave-enhanced conditions it is therefore possible to introduce three deuterium atoms (Scheme 13.4). As hydrogen isotope exchange is a reversible reaction this means that the three deuterium atoms can be readily exchanged under microwave irradiation. For storage purpose it might be best to back-exchange the C-2(D) so that the 4,5-[2H2] isotopomer can be safely stored as the solid without any dangers of deuterium loss. The recently... 

Ease of separation of tritiated products from a reaction medium is an important feature in the choice of labeling procedure. Sometime ago we used polymer-sup-ported acid and base catalysts [12, 13] to good effect and with the current interest in Green Chemistry one can expect to see more studies where the rate accelerations observed under microwave-enhanced conditions are combined with the use of solid catalysts such as Nafion, or zeolites. 

Neither tritium or deuterium gas, with zero dipole moments, can be expected to interact positively with microwave radiation. Their low solubilities are seen as a further disadvantage. Our thoughts therefore turned towards an alternative procedure, of using solid tritium donors and the one that has found most favor with us is formate, usually as the potassium, sodium or ammonium salt. Catalytic hydrogen transfer of this kind is remarkably efficient as the results for a-methylcinnamic acid show [50]. The thermal reaction, when performed at a temperature of 50 °C, takes over 2 h to come to equilibrium whereas the microwave-enhanced reaction is complete within 5 min. A further advantage is that more sterically hindered al-kenes such as a-phenylcinnamic acid which are reduced with extreme difficulty when using H2 gas and Wilkinson s catalyst are easily reduced under microwave-enhanced conditions. 

The potential of the microwave-enhanced decarboxylation route in the radioactive waste area is immediately apparent - washing the tritium waste with a protic solvent leads to exchange of the labile tritium. The solvent can then be used with one of the carboxylic acids mentioned above and after the microwave-enhanced decarboxylation the waste is now in the form of a solid (greatly reduced volume) which may have some further use. 

Apart from the traditional solid supports (see above), several publications also report the successful use of microwave enhancement for supported transformations involving soluble polymers49-54, fluorous phase conditions55,56, and ionic liquids grafted onto polymeric supports57,58. 

Palasek, S.A., Cox, Z.J., and Collins, J.M. (2007) Limiting racemization and aspar-timide formation in microwave-enhanced Fmoc solid phase peptide synthesis. J. Pept. Sci. 13,143-148. 

The most common extraction techniques for semivolatile and nonvolatile compounds from solid samples that can be coupled on-line with chromatography are liquid-solid extractions enhanced by microwaves, ultrasound sonication or with elevated temperature and pressures, and extraction with supercritical fluid. Elevated temperatures and the associated high mass-transfer rates are often essential when the goal is quantitative and reproducible extraction. In the case of volatile compounds, the sample pretreatment is typically easier, and solvent-free extraction methods, such as head-space extraction and thermal desorption/extraction cmi be applied. In on-line systems, the extraction can be performed in either static or dynamic mode, as long as the extraction system allows the on-line transfer of the extract to the chromatographic system. Most applications utilize dynamic extraction. However, dynamic extraction is advantageous in many respects, since the analytes are removed as soon as they are transferred from the sample to the extractant (solvent, fluid or gas) and the sample is continuously exposed to fresh solvent favouring further transfer of analytes from the sample matrix to the solvent. 

There are distinct advantages of these solvent-free procedures in instances in which catalytic amounts of reagents or supported agents are used, because they enable reduction or elimination of solvents, thus preventing pollution at source . Although not delineated completely, reaction rate enhancements achieved by use of these methods may be ascribed to nonthermal effects. Rationalization of micro-wave effects and mechanistic considerations are discussed in detail elsewhere in this book [25, 244], There has been an increase in the number of publications [23c, 244, 245] and patents [246-256], and increasing interest in the pharmaceutical industry [257-259], with special emphasis on combinatorial chemistry and even polymerization reactions [260-263], and environmental chemistry [264]. The development of newer microwave systems for solid-state reaction [265], and introduction of the concepts of process intensification [266], may help realization of the full potential of microwave-enhanced chemical syntheses under solvent-free conditions. 

Parallel to these developments in solid-phase synthesis and combinatorial chemistry, microwave-enhanced organic synthesis has attracted much attention in recent years. As is evident from the other chapters in this book and the comprehensive reviews available on this subject [5, 6], high-speed microwave-assisted synthesis has been applied successfully in many fields of synthetic organic chemistry. Any technique which can speed the process of rather time-consuming solid-phase synthesis is of substantial interest, particularly in research laboratories involved in high-throughput synthesis. 

One of the most attractive features of borohydride reductions is that under microwave-enhanced conditions they can be performed in the solid state, and rapidly. We were attracted by the work of Loupy et al. [71], and in particular Varma and Saini [72, 73] who have shown that irradiation of a number of aldehydes and ketones in a microwave oven in the presence of alumina doped NaBH4 for short periods of time, led to rapid reduction (0.5-2 min) in good yields (62-93%). In our study [74], seven aldehydes and four ketones were reduced (Table 18.3). Again reduction was complete within 1 min, the products were of high purity (>95%) and of high isotopic incorporation (95%, same as the NaBD4), and the reactions completely selective. 

The synthesis of [ C]-labeled esters using a C-alkylation of diethyl malonate under microwave-enhanced solid-liquid phase transfer catalysis (PTC) conditions and a subsequent microwave-enhanced decarboalkoxylation (Krapcho reaction) [167] indicates that an alternative approach to the preparation of [ C]-labeled fatty acids/esters [168] with less harsh conditions may be possible. 

Microwave-enhanced Solid-phase Peptide Synthesis... 

I 20 Microwave-enhanced Solid-phase Peptide Synthesis Tab. 20.1. Phosphonium and aminium activators. 

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