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

Abstract

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.

Revisiting Biginelli-like reactions: solvent effects, mechanisms, biological applications and correction of several literature reports

“…1), prompting us to investigate the underlying reasons for this discrepancy. As recently discussed in the context of MCRs, 116 melting point characterizations can potentially lead to erroneous conclusions when not supported by additional analyses.…”

Ce-Mn-binuclear LDH based-Cu complex as a potent nanocatalyst for green-synthesis of spiroacridineindoletriones: a comparative study

“…An important strategy for the synthesis of these compounds is the synthesis through multicomponent reactions (MCRs) which has attracted a lot of attention in the last few decades. Some advantages of MCRs over classical synthesis include atom economy, simple procedures, savings in solvent, time, and energy, simple equipment, lower costs, and to synthesize libraries of compounds bearing several biological responses 30,31 .…”