Transforming Predictions into Testable Hypotheses: The Case of Polar Organic Reactivity

<p>Herbert Mayr’s research on reactivity scales tells a success story of how polar organic synthesis can be rationalized by a simple empirical relationship. In this work, we propose an extension to Mayr’s reactivity approach that is rooted in uncertainty quantification (UQ). It transforms the <i>unique</i> values of reactivity parameters (<i>s</i>_N, <i>N</i>, <i>E</i>) into value <i>distributions</i>. Through uncertainty propagation, these distributions can be exploited to quantify the uncertainty of bimolecular rate constants. Our UQ-based extension serves three purposes. First, predictions of polar organic reactivity can be transformed into testable hypotheses, which increases the overall reliability of the method and guides the exploration of new research directions. Second, it is also possible to quantify the discriminability of two competing reactions, which is particularly important if subtle reactivity differences matter. Third, since rate constant uncertainty can also be quantified for reactions that have yet to be observed, new opportunities arise for benchmarking computational chemistry methods (benchmarking <i>under uncertainty</i>). We demonstrate the functionality and performance of the UQ-extended reactivity approach at the example of the 2001/12 reference data set released by Mayr and co-workers [<i>J. Am. Chem. Soc.</i> <b>2001</b>, <i>123</i>, 9500; <i>J. Am. Chem. Soc.</i> <b>2012</b>, <i>134</i>, 13902]. As a by-product of the new approach, we obtain revised reactivity parameters for the electrophiles and the nucleophiles of the reference set.</p>

Transforming Predictions into Testable Hypotheses: The Case of Polar Organic Reactivity

<p>Herbert Mayr’s research on reactivity scales tells a success story of how polar organic synthesis can be rationalized by a simple empirical relationship. In this work, we propose an extension to Mayr’s reactivity approach that is rooted in uncertainty quantification (UQ). It transforms the <i>unique</i> values of reactivity parameters (<i>s</i>_N, <i>N</i>, <i>E</i>) into value <i>distributions</i>. Through uncertainty propagation, these distributions can be exploited to quantify the uncertainty of bimolecular rate constants. Our UQ-based extension serves three purposes. First, predictions of polar organic reactivity can be transformed into testable hypotheses, which increases the overall reliability of the method and guides the exploration of new research directions. Second, it is also possible to quantify the discriminability of two competing reactions, which is particularly important if subtle reactivity differences matter. Third, since rate constant uncertainty can also be quantified for reactions that have yet to be observed, new opportunities arise for benchmarking computational chemistry methods (benchmarking <i>under uncertainty</i>). We demonstrate the functionality and performance of the UQ-extended reactivity approach at the example of the 2001/12 reference data set released by Mayr and co-workers [<i>J. Am. Chem. Soc.</i> <b>2001</b>, <i>123</i>, 9500; <i>J. Am. Chem. Soc.</i> <b>2012</b>, <i>134</i>, 13902]. As a by-product of the new approach, we obtain revised reactivity parameters for the electrophiles and the nucleophiles of the reference set.</p>

Ionic liquids: “normal” solvents or nanostructured fluids?

This review provides an overview of the literature from 2010 to the present day, covering the effect of ionic liquids (ILs) on organic reactivity. Two major viewpoints emerge, based on linear solvation energy relationships or nanostructure of ILs.

Opinion: Chemical Meoscopics for the Mesoparticles Reactivity Explanation

The estimation of chemical particles reactivity and the determination of chemical reactions direction are the actual theme in new scientific trend – Chemical Mesoscopics. Paper includes the proposal about the using the theory of free energy linear dependence from physical organic chemistry and their applications for prognosis of reactions flowing. The semi-empiric constants is given according to mesoscopic physics definitions as well as the transformed Kolmogorov–Avrami equation is discussed. It is the development of Chemical Mesoscopics for organic reactivity estimation including nanostructures reactivity.