Suitable reactions, microwave scale

Similar results were achieved when Biginelli reactions in acetic acid/ethanol (3 1) as solvent (120 °C, 20 min) were run in parallel in an eight-vessel rotor system (see Fig. 3.17) on an 8 x 80 mmol scale [87]. Here, the temperature in one reference vessel was monitored with the aid of a suitable probe, while the surface temperature of all eight quartz reaction vessels was also monitored (deviation less than 10 °C Fig. 4.4). The yield in all eight vessels was nearly identical and the same set-up was also used to perform a variety of different chemistries in parallel mode [87]. Various other parallel multivessel systems are commercially available for use in different multimode microwave reactors. These are presented in detail in Chapter 3. 

Substitution of halogens on heteroaromatic rings is a common way to introduce new functionalities. The product from reaction 6 (Scheme 6) was required on a 100-g scale as an intermediate. In the literature, this exchange was done on a 5-g scale using ammonia in ethanol in a sealed tube under pressure for 6 h at 125-130°C with a yield of 76% (Bendich et al. 1954). Because of the lack of a suitable autoclave for high-pressure reactions, we choose the microwave reactor for scale-up trials. Using our Synthos 3000 equipment, we found suitable conditions with only minimal optimization at 170°C for 180 min and obtained the desired product on a 60-g scale in 83% yield. 

The final step poses difficulties to the process since it requires long reaction times and often needs to be performed in a sealed tube. Recently, improvements of the process were reported, including the use of microwaves [62]. However, micro-waves-promoted reactions are not suitable for a convenient scale-up at the moment. 

The CMR, which could operate up to the pilot-scale, functioned by passage of reaction mixtures through a microwave zone under pressure, followed by rapid cooling of the pressurized effluent [78]. MBRs were introduced for small-scale (25-200 mL) reactions and were suitable for synthesis and kinetics studies. The most advanced unit, reported in 1995, operated at up to 260 °C and 10 MPa (100 atmospheres) in a laboratory environment. Its... 

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