Reply to T. W. Bentley: Limitations of the s(E+N) and Related Equations

Abstract

electrophilicity · kinetics · linear free-energy relationships · nucleophilicity · solvent effectsThe preceding commentary [1] is the forth in a series [2][3][4] that tries to discredit our approach to a semiquantitative model of polar organic reactivity. None of these publications reports new experimental results, and all deal exclusively with a reinterpretation of our kinetic data. As the detailed analysis of the manifold mistakes and incorrect statements in references [1][2][3][4] would bore the nonspecialist reader, I will comment the most important points in this response and ask the interested reader to find my comprehensive reply in the Supporting Information, which also provides a detailed validation of the statements in this reply. Let me first explain the essence of the controversy, which is not described in reference [1]. The Patz-Mayr ApproachIn recent years we have studied the kinetics of the reactions of carbocations and Michael acceptors with different types of nucleophiles, including alkenes, enol ethers, enamines, arenes, ylides, organometallic compounds, hydride donors, amines, phosphines, alcohols, alkoxides, and many more nucleophiles. The most commonly used solvents were dichloromethane, acetonitrile, DMSO, and water. The reactivities of electrophiles and nucleophiles thus studied cover a range of more than 30 orders of magnitude.[5] As bimolecular reactions in these solvents cannot be faster than 10 9 -10 10 L mol À1 s À1 (diffusion limit) and reactions slower than 10 À5 L mol À1 s À1 are difficult to measure, it is impossible to base a comprehensive nucleophilicity scale on measured rate constants for a single reference electrophile.Therefore, we have defined a series of benzhydrylium ions and quinone methides as reference electrophiles, which differ widely in reactivity. We studied the kinetics of their reactions with various nucleophiles and performed a least-squares minimization on the basis of Equation (1). [7a,b] In this equa-tion, electrophiles are characterized by one parameter (E), which we defined as solvent-independent, while nucleophiles are characterized by two parameters, the nucleophilicity parameter N and the nucleophile-specific sensitivity parameter s N (previously termed s), which are treated as solventdependent. Fixed parameters were E = 0 for (4-MeOC 6 H 4 ) 2 CH + and s N = 1.0 for 2-methyl-pent-1-ene. Reference [3] correctly describes that our basis correlation for deriving the reactivity parameters N, s N , and E was based on 209 rate constants for the reactions of 38 p nucleophiles with 23 electrophiles in the reactivity range À10 < E < 6. It is not clear why Scheme 1 in both Ref.[4] and Ref.[1] now pretend that our basis correlation was restricted to electrophiles in the narrow range of 0 < E < 6. This is not true![8] Details of our correlation are given in Appendix A of the Supporting Information.Since both s N and N are nucleophile-specific parameters, Equation (1) is equivalent to Equation (2), in which thenucleophilicity parameter Nu corresponds to log k of the...

Nucleophilic Addition of Enols and Enamines to α,β‐Unsaturated Acyl Azoliums: Mechanistic Studies

“…[12] All kinetic experiments were performed under pseudo-first-order conditions using an excess of nucleophiles. [12] All kinetic experiments were performed under pseudo-first-order conditions using an excess of nucleophiles.…”

Nukleophile Addition von Enolen und Enaminen an α,β‐ungesättigte Acylazoliumionen: Mechanistische Studien

“…[12] Sämtliche kinetischen Experimente führten wir unter Bedingungen pseudo-erster Ordnung mit einem Überschuss an Nukleophil durch. [12] Sämtliche kinetischen Experimente führten wir unter Bedingungen pseudo-erster Ordnung mit einem Überschuss an Nukleophil durch.…”

“…Die Abbildung 2 zeigt, dass (lg k)/s N linear mit N korreliert, [12] sodass Gleichung (1) erfüllt ist, welche Geschwindigkeitskonstanten zweiter Ordnung aus dem Elektrophilspezifischen Parameter E und den beiden Lçsunsgmittel-abhängigen Nukleophil-spezifischen Parametern N und s N errechnet. Wir kçnnen daher folgern, dass der geschwindigkeitsbestimmende Schritt der Reaktion von 2 mit 4-6 mechanistisch analog den Reaktionen von 4-6 mit Benzhydrylium-Ionen ist, die bekanntermaßen über CC-Bindungsknüpfung ablaufen (siehe Reaktionen auf Seite S43, Hintergrundinformationen).…”

Nucleophilic Reactivities of Schiff Bases

“…1) [17 -24], where electrophiles are characterized by one solvent-independent electrophilicity parameter E, and nucleophiles are characterized by two solvent-dependent nucleophile-specific parameters N and s N . As explained previously in detail [22], the uncommon shape of Eq. 1 avoids far-reaching extrapolations by defining nucleophilicity N as the negative intercept on the abscissa in log k versus E plots.…”