Variations of the Traditional Biginelli Condensation

In general, aldehydes are more volatile, toxic, or unstable than their corresponding alcohols. And if these are used without previous distillation/purification, the presence of other byproducts could affect not only the real concentration of the active aldehyde in the reaction, but the impurities could also interfere in the course of the reactions reacting with other species present in the process. For this reason, the use of alcohols, with their subsequent oxidation, instead of the corresponding aldehydes is an interesting improvement in this and in other MCRs, and it would widen significantly the versatility and scope of the aldehyde-based MCRs [57]. 

The authors explored the scope of this reaction for a variety of aromatic alcohols 49 and also demonstrated the compatibility of this method with a variety of functional groups in the alcohols snch as ethers, nitro, hydroxyl, and 

Other interesting variations based on environmentally friendly alternatives, such as the use of microwaves [60], ionic liquids [61], aqueous media [62], or solvent-free [63] processes have also been reported to carry out the strategies with success. 

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