Influence of Polarity on the Scalability and Reproducibility of Solvent-Free Microwave-Assisted Reactions

Abstract

Organic reactions performed in the absence of solvent in domestic ovens without appropriate temperature control are generally considered as not reproducible, particularly when different instruments are used. For this reason, reproducibility has historically been one of the major issues associated with Microwave-Assisted Organic Synthesis (MAOS) especially when domestic ovens are involved. The lack of reproducibility limits the general applicability and the scale up of these reactions. In this work several solvent-free reactions previously carried out in domestic ovens have been translated into a single-mode microwave reactor and then scaled up in a multimode oven. The results show that most of these reactions, although not considered as reproducible, can be easily updated and applied in microwave reactors using temperature-controlled conditions. Furthermore, computational calculations can assist to explain and/or predict whether a reaction will be reproducible or not.

Reproducibility and Scalability of Microwave-Assisted Reactions

“…Similar conclusions were reported by Leadbeater in a study into the rapid optimization of reaction conditions (Leadbeater & Schmink, 2007). In order to extend the preliminary results to see whether any solvent-free reaction previously performed in a domestic oven can be reproduced in dedicated apparatus, the same authors studied four new reactions that cover a wide range of chemical transformations (Díaz-Ortiz et al, 2011). It was found that N-alkylation of (1H)-benzotriazoles, condensation of anilines with urea (or thiourea) and Beckmann rearrangement of ketoximes are reproducible in both single-mode and multimode microwave instruments using temperature-controlled conditions.…”

Understanding MAOS through computational chemistry

“…73 In the first case, the Finally, Díaz-Ortiz and col. reinvestigated five solvent-free reactions previously carried out in domestic ovens, with the aim of demonstrating the reproducibility and scalability of solventfree reactions. 74 The authors translated the reactions into a single-mode microwave reactor and then scaled them up in a multimode oven. The results show that most of these reactions can be easily scaled in microwave reactors using temperaturecontrolled conditions.…”

Nonthermal Effects of Microwaves in Organic Synthesis

“…More recently, more extended computational calculations were shown to represent a very useful tool to study separately the occurrence of the thermal and nonthermal effects of MW irradiation through the determination of the thermodynamic and kinetic parameters of the reactions [84,85] (see also Chapter 6 dedicated to this point).…”

“…Such an assumption was verified experimentally and justified by considering theoretical calculations predicting an asynchronous mechanism in the cycloaddition of N-methylazomethine ylide to C 70 fullerene [61]: This reaction was examined by computational calculations to assess the effect of MW irradiation. It was concluded that the thermodynamic product would be favored under MW exposure, indicating the presence of only thermal effects at higher temperatures [85].…”