Maria M. Toteva

The Generation and Reactions of Quinone Methides.

Abstract The combination of neutral non-aromatic and zwitterionic aromatic contributing valence bond structures confers a distinctive chemical reactivity to quinone methides, which has attracted the interest of a tremendous number of chemist and biochemists. This chapter reviews reactions that generate quinone methides, and the results of mechanistic studies of the breakdown of quinone methides in nucleophilic substitution reactions. The following pathways for the formation of quinone methides are discussed; (a) photochemical reactions; (b) thermal heterolytic bond cleavage; (c) reactions that unmask a quinone oxygen; (d) nucleophilic aromatic substitution reactions of water at 4-methoxybenzyl carbocations; (e) oxidation reactions of phenols; (f) reductive-elimination reactions of quinones; (g) miscellaneous reactions. Results, and their interpretation, of studies from the laboratories of A. J. Kresge and J. P. Richard are reviewed. The highlights include: (a) Experiments to characterize the effect of O-protonation and O-methylation of the p-quinone methide oxygen to form the p-hydroxybenzyl and pmethoxybenzyl carbocations, respectively, on electrophile stability and reactivity. (b) A comparison of p-quinone methide, o-quinone methide and o-thioquinone methide. (c) Evidence that structure-reactivity relationships for addition of nucleophiles to quinone methides closely resemble those determined for nucleophile addition to strongly resonance stabilized carbocations. (d) Evidence that the aromatic zwitterionic valence bond structure makes only a relatively small contribution to the structure of p-quinone methide. (e) A comparison of the Marcus intrinsic barriers for addition of water to p-quinone methide and to formaldehyde. (f) A discussion of the effect of O-methylation of p-quinone methide and formaldehyde on the intrinsic barrier for water addition.

Dynamics for the reactions of ion pair intermediates of solvolysis

Publisher Summary This chapter discusses the dynamics for the reactions of ion pair intermediates of solvolysis. It focuses on determining partition rate constant ratios for a variety of reactions of ion pairs, and of absolute rate constants from these ratios. This has been accomplished by use of one of the rate constants from this product ratio as a “clock” for the second reaction. The addition of water to a free carbocation intermediate of solvolysis has been distinguished from addition to an ion-pair intermediate by an examination of common ion inhibition of solvolysis. The observation of “hidden” reactions during solvolysis, through the use of chiral or isotopically labeled substrates has created considerable excitement in communities interested in the mechanisms of non-enzymatic and enzyme catalyzed reactions. The racemization of chiral substrate or the exchange of bridging and nonbridging oxygen during solvolysis may occur through an ion-pair reaction intermediate that is sufficiently long-lived to undergo reorganization in a solvent cage, or it may proceed by an effectively “concerted” mechanism over an energy maximum that closely resembles the carbocation–anion pair intermediate. Another historically important reaction is the reorganization of “chiral” ion pair intermediates of solvolysis of a chiral substrate that leads to racemization of substrate during solvolysis.

How does structure determine organic reactivity? Partitioning of carbocations between addition of nucleophiles and deprotonation

Publisher Summary This chapter reviews the results of the studies of the kinetics and products of stepwise nucleophilic substitution and elimination reactions of alkyl derivatives, focuses on factors that control the rate constant ratio k s / k p for the partitioning of carbocations, and provides an understanding of how the absolute rate constants k s and k p that constitute this ratio, change with changing carbocation structure. The analyses presented in the chapter are possible because of some recent experimental results that include: determinations of absolute rate constants with values up to k s = 10 10 s -1 for the reaction of carbocations with water and other nucleophilic solvents, determination of the large values of the rate constant ratio k s / k p from the low yields of alkene product, kinetic studies of stepwise hydration reactions of alkenes, and recent characterization of carbocations that partition to form an alkene. The chapter also discusses the explanations for the large changes in the rate constant ratio for the partitioning of carbocations between reaction with BrOnsted and Lewis bases that result from small changes in carbocation structure.