Microwave-mediated Biginelli reactions revisited. On the nature of rate and yield enhancements

The microwave-mediated Biginelli dihydropyrimidine synthesis was reinvestigated using a purpose-built commercial microwave reactor with on-line temperature, pressure, and microwave power control. Transformations carried out under microwave heating at atmospheric pressure in ethanol solution show no rate or yield increase when the temperature is identical to conventional thermal heating. In the case of superheating by microwave irradiation at atmospheric pressure the observed yield and rate increases are rationalized as a consequence of a thermal (kinetic) effect. Under sealed vessel conditions (20 bar, 180 degrees C) the yield of products is decreased and formation of various byproducts observed. The only significant rate and yield enhancements are found when the reaction is performed under "open system" conditions where the solvent is allowed to rapidly evaporate during microwave irradiation. However, the observed rate and yield enhancements in these experiments are a consequence of the solvent-free conditions rather than caused specifically by microwave irradiation. This was confirmed by control experiments of the solventless Biginelli reaction under microwave and thermal heating.