In Melting Points We Trust: A Review on the Misguiding Characterization of Multicomponent Reactions Adducts and Intermediates

We discuss herein the problems associated with using melting points to characterize multicomponent reactions' (MCRs) products and intermediates. Although surprising, it is not rare to find articles in which these MCRs final adducts (or their intermediates) are characterized solely by comparing melting points with those available from other reports. A brief survey among specialized articles highlights serious and obvious problems with this practice since, for instance, cases are found in which as many as 25 quite contrasting melting points have been attributed to the very same MCR adduct. Indeed, it seems logical to assume that the inherent non-confirmatory nature of melting points could be vastly misleading as a protocol for structural confirmation, but still many publications (also in the Q1 and Q2 quartiles) insist on using it. This procedure contradicts best practices in organic synthesis, and articles fraught with limitations and misleading conclusions have been published in the MCRs field. The drawbacks inherent to this practice are indeed serious and have misguided MCRs advances. We therefore suggest some precautions aimed at avoiding future confusions.