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 [1-4] 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 rea...

A comprehensive view on stabilities and reactivities of triarylmethyl cations (tritylium ions)

“…As discussed in detail previously, this formalism does not imply that electrophile solvation is insignificant. Our treatment just shifts all solvation effects into the nucleophile‐specific parameters, a procedure that makes these correlations easily applicable.…”

Increasing the Reactivity of Nitrogen Catalysts

“…As calculations and experiments performed by Zipse and co-workers indicated a very unlikely intervention of DMAP acting as a gen-eral base, it is clear that pK a is not the most relevant parameter to consider when examining nucleophilic pyridine catalysts. On the other hand, the nucleophilicity parameters N (nucleophilicity) and s N (nucleophile-specific slope parameter) developed by Mayr [24] are more relevant values when comparing different Lewis bases. The nucleophilicity (N) is linked to the rate at which the catalyst will attack the electrophile (k 1 ).…”

A Frontier Molecular Orbital Theory Approach to Understanding the Mayr Equation and to Quantifying Nucleophilicity and Electrophilicity by Using HOMO and LUMO Energies

“…The reasons behind these results have not been well investigated, even though steric factors were used to explain these effects. Despite these computational efforts to rationalize the reactivity parameters, a theoretical foundation and further understanding of the Mayr equation are needed to significantly advance our understanding of reactivities 6g…”