Alpha effect

The effect was first observed by Jencks and Carriuolo in 1960[5][6] 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 pKa.

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.

The ground state destabilization theory proposes that the electron-electron repulsion between the alpha lone-pair and nucleophilic electron pair destabilize each other by electronic repulsion (filled–filled orbital interaction) thereby decreasing the activation barrier by increasing the ground state energy and making it more reactive.

[9] Other driving forces including the tighter transition state[10] and higher polarizability of α-nucleophiles, involvement of intramolecular catalysis also plays a role.

α-nucleophiles with O, HN, and S in the α position were classified into three groups according to their degree and pattern of deviation from the Brønsted-type correlation in SN2 reactions with the substrate, ethyl chloride (C2H5Cl) (Figure 3).

Lastly, the third group had nucleophiles showing inverse α-effect, meaning that they are above the plotted line or have less reactivity considering their high basicity.

To elaborate on the first requirement, the electronegative heteroatom reduces the electron density of the atom that attacks the nucleophile making the HOMO lobe smaller.