Scale-up of methods employing solvents

Similar to the solvent-free approaches discussed in Section 3.2, a combinatorial approach also has been employed to scale-up the synthesis of desired compounds100. The microwave-assisted reactions are performed on solvent-swollen polymeric beads and are classified herein as being carried out in the presence of a solvent. Examination of these supports after 20 min of microwave irradiation (700 W) revealed that neither the appearance nor swelling behaviour of the beads had altered65. 

Applications of this technique include peptide hydrolysis101, peptide coupling102, Suzuki couplings, Stille coupling63 103 104, parallel synthesis of 1,3,5-triazines105 and fluorous Stille coupling106. 

Several workers have employed monomodal cavities for microwave chemistry on the sub-gram scale. In some cases in which monomodal cavities have been used7, special benefits of so-called focussed microwaves have been claimed. As mentioned earlier, the dielectric properties of a sample can alter substantially with temperature and/or with changing chemical composition. Hence, regardless of whether multi-modal or unimodal cavities are employed, frequent tuning may be necessary if heating efficiency is to be retained. This aspect has often been overlooked by proponents of focussed microwaves. The nett result is that transfer of microwave conditions between monomodal to multi-modal cavities is usually facile. With the MBR (which had a tunable multimodal cavity), Cablewski et al. performed five reactions that had been conducted earlier on the gram scale or below with focussed microwaves (T. Cablewski, B. Heilman, P. Pilotti, J. Thorn, and C.R. Strauss, personal communication see also Ref. 117 for conference poster). These were scaled-up between 40- and 60-fold and reaction conditions 

With the MBR, other examples of scale-up involving a triphenylphosphine-free one-pot Wittig olefination, a one-step three-component synthesis of imidazo annulated 

In a recent example Kappe and co-workers112 scaled up a series of reactions from a single mode to a multimode parallel batch reactor. Typically reactions were scaled from 1 to 100 mmol. The transformations included 

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