Problems involved in understanding orders of nucleophilic reactivity

Abstract

-The N+ relationship has been found to have considerable generality for the correlation of rate constants of electrophilenucleophile combination reactions. There are, however, some serious deviations from the relationship, particularly for thiolate anions and for azide ion reactions. Data for a large number of reactions show an absence of selectivity-reactivity relationships and a general absence of observable coulombic effects.Detailed examination of the data by the use of the N+ relationship reveals some examples of apparent steric effects on reactivity which, in the case of secondary amines, cause deviations of up to ca. l log unit. The deviant behavior of thiolate and azide ions do not appear tobe rationalizable by any of the current theories of nucleophilic reactivity.I NTRODUCTI ON A major, perhaps predominant, proportion of the important reactions of Organic Chemistry involve nucleophilic addition or Substitution steps. Thus, the problern of understanding nucleophilic reactivity is one of the central foci of Physical-Organic Chemistry and has a rather lang history. Important early work on this problern includes J. 0. Edwards' recognition of the influence of both basicity and polarizability (l) and A. J. Parker's demonstration of the sometimes overwhelming importance of solvent effects (2). By the late 1960's there appeared to be a general consensus (3) that quantitative correlations of nucleophilic reactivities were unlikely to exist.In our opinion, one of the major stumbling blocks in much of the early work was the failure to distinguish mechanistic types of nucleophilic reactions. Following this belief, we have concentrated our efforts toward the study of reactions in which an electrophile-nucleophile combination step is rate-determining. The simplest example of such reactions is a cationanion combination such as the reaction of tropylium ion with cyanide ion. The large majority of amine reactions with cations, nucleophilic aromatic Substitution reactions in protic solvents, nucleophilic substitution reactions of very reactive esters, and Michael reactions, are other examples.From extensive data on such reactions, obtained principally in our laboratories, those of W. P. Jencks, and those of J. L. Kice, we have shown (4) that rate constants can be correlated by the simple N+ equation:Log k = Log ko + N+ ( l ) in which Log ko is a parameter characteristic of the electrophile and N+ is a parameter characteristic of the nucleophile. In words, the equation states that the relative reactivities of electrophiles are independent of nucleophile and those of nucleophiles are independent of electrophile. There is an obvious implication of the absence of specific interactions between electrophile and nucleophile at the transition states for these reactions.We have also shown that Eq. l applies to the addition step for the reactions of nucleophiles with aryl acetates, N-methylimidazolium acetate, and 2,2,2-trifluoroethylthiol acetate. The observed rate constants for these reactions, in which the combinat...

Cation–anion combination reactions. 26. A review

“…Note that the half-cell in reaction [16] is quite different from that in reaction [14] used by Edwards. Although very few of the potentials for reaction [I61 have been measured in solution, it was possible to devise a thermodynamic cycle (24.…”

“…It was pointed out in the original paper (24) that the correlation is not expected on the basis of any of the quantuni mechanical theories (90-94) of the reactions. These theories must deal with vertical transitions between states, while the potentials for reaction [16] are for non-vertical, adiabatic, processes.…”

“…equation, has now been tested for a wide variety of Lewis acid-base reactions (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). Although it is far from being general, and fails badly in some specific cases without apparent cause, it is probably as good as most of the more complex equations when applied to electrophile-nucleophile combination reactions.…”

The reaction of trihalogenomethyl anions with carbonyl compounds: competitive reactivity comparisons and applications to the synthesis of α-trihalogenomethyl alcohols

“…In experiments without added mineral acid, reaction ( 4) is relatively unimportant. The final absorbance (A') in a cell of 1 cm pathlength when there is no added carbonyl compound will be given by equation (7) and not very different from the product E ~~J T X A A ]…”

Stability−Reactivity Relation on the Reaction of β,β-Disubstituted Vinyl Cations with Ethanol

“…The relationship between reactivity and selectivity is a well-known concept in organic chemistry. In relation to this concept, Ritchie reported 20 years ago that the relative rates of reactions of stable carbocations with a series of nucleophiles were independent of the reactivity of the cations. , Thus, the reactivity differences of stable cations such as crystal violet and p -nitrobenzenediazonium ion in reactions with a large variety of nucleophiles ranging from the very reactive MeO - to the less reactive H 2 O were independent of the cation stabilities. These findings have cast serious doubt on the generality of the reactivity−selectivity relationship.…”