Page 202 - Mechanism and Theory in Organic Chemistry

The Solvent, Substrate, Nucleophile, and Leaving Group 191

as charge density: OH-, F- >> C1- > Br- > I- > SeCN-. The large ions,
which are both relatively unsolvated and more polarizable, are much better
nucleophiles. However, in aprotic solvents there is no possibility for stabilization
of the negative charge on the small ions by hydrogen bonding, and they become
more reactive, sometimes even overtaking the more polarizable larger ions.50
Pearson and Songstad have suggested that the ilucleophilicity of a reagent
can also be described in terms of hard and soft acid and base theory.51 In Lewis
acid-base terms, the mechanism of an SN2 displacement can be written as in
Equation 4.23. We already know that methyl cations (and, by analogy, other

alkyl cations) are considered moderately soft acids. If we make the reasonable
assumption that the charge on the alkyl group does not change much in going
from the ground state to the transition state, an alkyl group will also be soft in the
transition state of an SN2 reaction. Solvents such as methanol and water act as
hard acids when their protons are used for hydrogen bonding, and therefore hard
bases such as F- or OH- interact preferentially with them rather than with
moderately soft alkyl substrates. Aprotic solvents such as dimethyl sulfoxide are
very soft acids: when displacements are run in them, the hard bases do not inter-
act with them and thus are freer to react with alkyl substrates.
Note that the n,, values in Table 4.5, which give relative rates for Reaction
4.24 with various bases in methanol, are highest for very soft bases [e.g., (C,H,),P,

(C,H,),As] which carry no charge on the donor atom and which have little
attraction for the proton. Thus compared to PtI1, CH, + is only a moderately
soft acid. It is thus apparent that nucleophilic strength at one substrate should not
parallel the strength at another unless the two substrates are of comparable hard-
ness or softness.
Edwards has proposed an equation for the correlation of SN2 reaction rates
that can be used in different types of solvent systems and that emphasizes the
dependence of nucleophilicity on basicity and p~larizability.~' The equation is
k
log - = aE, + pH (4.25)
ko
where His the pK, of the conjugate acid of the nucleophile plus 1.74 and En is a
parameter that measures polarizability. Edwards first suggested that En be
defined in terms of the oxidation potential of the nucleophile, but more recently
proposed a new definition based on the molar refractivity of the nucleophile.
The constants a and /3 are determined experimentally for each substrate to give
the best fit with experimental data. An advantage of the two-parameter equation
is that it allows for a variation in relative nucleophilic reactivity when the sub-

For further examples of the difficulty in assigning a reagent with an "intrinsic nucleophilicity,"
see C. D. Ritchie, Accts. Chem. Res., 5, 348 (1972).
R. G. Pearson and J. Songstad, J. Amer. Chem. Soc., 89, 1827 (1967).
52 J. 0. Edwards, J. Amer. Chem. SOC., 76, 1540 (1954); J. 0. Edwards, J. Amer. Chem. Soc., 78, 1819
(1956). For another theoretical treatment of nucleophilic reactivities, see R. F. Hudson, Chimia, 16,
173 (1962).