Alpha effect

The alpha effect refers to the increased nucleophilicity of a molecule due to the presence of an adjacent (alpha) atom with lone pair electrons. The molecule does not necessarily exhibit increased basicity compared with a similar molecule without the adjacent, electron donating atom. The effect is well established with many theories to explain the effect but without a clear winner.

The effect was first observed by Jencks and Carriuolo in 1960 in a series of chemical kinetics experiments involving the reaction of the ester p-nitrophenyl acetate with a range of nucleophiles. Regular nucleophiles such as the fluoride anion, aniline, pyridine, ethylene diamine and the phenolate ion were found to have pseudo first order reaction rates corresponding to their basicity as measured by their pK_a. Other nucleophiles however reacted much faster than expected based on this criterion alone. These include hydrazine, hydroxylamine, the hypochlorite ion and the hydroperoxide anion.

In 1962 Edwards and Pearson (the latter of HSAB theory) introduced the phrase alpha effect for this anomaly. He offered the suggestion that the effect was caused by a transition state (TS) stabilization effect: on entering the TS the free electron pair on the nucleophile moves away from the nucleus causing a partial positive charge which can be stabilized by an adjacent lone pair as for instance happens in any carbocation.