Alpha effect

The alpha effect refers to the increased nucleophilicity of an atom due to the presence of an adjacent (alpha) atom with lone pair electrons.[1] This first atom does not necessarily exhibit increased basicity compared with a similar atom without an 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[2][3] 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. 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.[4]

Over the years many additional theories have been put forward attempting to explain the effect. A ground state destabilizing effect assumes that 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. Stabilization of the transition state is possible by assuming some TS free radical character or assuming that the TS has more advanced nucleophile-substrate bond formation. The polarizability of the nucleophile or involvement of intramolecular catalysis also plays a role. One recent in silico contribution did find a correlation between the alpha effect and the so-called deformation energy which is the electronic energy required to bring the two reactants together in the transition state.[5]

The alpha effect is also dependent on solvent but not in a predictable way: it can increase or decrease with solvent mix composition or even go through a maximum.[6] At least in some cases, the alpha effect has been observed to vanish if the reaction is conducted in the gas phase, leading some to conclude that it is primarily a solvation effect.[7]

References
  1. Chemical Reactivity . 14 July 2006. Michigan State University. 27 Jul 2006 <http://www.cem.msu.edu/~reusch/VirtTxtJml/react3.htm%5B%5D>.
  2. William P. Jencks; Joan Carriuolo (1960). "Reactivity of Nucleophilic Reagents toward Esters". Journal of the American Chemical Society. 82 (7): 1778–86. doi:10.1021/ja01492a058.
  3. William P. Jencks; Joan Carriuolo (1960). "General Base Catalysis of the Aminolysis of Phenyl Acetate". Journal of the American Chemical Society. 82 (3): 675–81. doi:10.1021/ja01488a044.
  4. John O. Edwards; Ralph G. Pearson (1962). "The Factors Determining Nucleophilic Reactivities". Journal of the American Chemical Society. 84: 16–24. doi:10.1021/ja00860a005.
  5. Ren, Y; Yamataka, H (Jul 2007). "The alpha-effect in gas-phase SN2 reactions: existence and the origin of the effect". The Journal of Organic Chemistry. 72 (15): 5660–7. doi:10.1021/jo070650m. ISSN 0022-3263. PMID 17590049.
  6. Buncel, Erwin; Um, Ik-Hwan (2004). "The α-effect and its modulation by solvent". Tetrahedron. 60 (36): 7801. doi:10.1016/j.tet.2004.05.006.
  7. A., Carroll, Felix (2010). Perspectives on structure and mechanism in organic chemistry (2nd ed.). Hoboken, N.J.: John Wiley. ISBN 9780470276105. OCLC 286483846.
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