Page 427 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

408 that govern nucleophilicity and the relationship between nucleophilicity and basicity. 25
As we will see in Section 4.4.3, there is often competition between displacement
CHAPTER 4
(nucleophilicity) and elimination (proton removal, basicity). We want to understand
Nucleophilic Substitution how the structure of the reactant and nucleophile (base) affect this competition.
The factors that influence nucleophilicity are best assessed in the context of the
limiting S 2 mechanism, since it is here that the properties of the nucleophile are most
N
important. The rate of an S 2 reaction is directly related to the effectiveness of the
N
nucleophile in displacing the leaving group. In contrast, relative nucleophilicity has no
effect on the rate of an S 1 reaction. Several properties can influence nucleophilicity.
N
Those considered to be most significant are: (1) the solvation energy of the nucleophile;
(2) the strength of the bond being formed to carbon; (3) the electronegativity of the
attacking atom; (4) the polarizability of the attacking atom; and (5) the steric bulk of
26
the nucleophile. Let us consider each how each of these factors affect nucleophilicity.
1. Strong solvation lowers the energy of an anionic nucleophile relative to the TS,
in which the charge is more diffuse, and results in an increased E . Viewed
a
from another perspective, the solvation shell must be disrupted to attain the
TS and this desolvation contributes to the activation energy.
2. Because the S 2 process is concerted, the strength of the partially formed new
N
bond is reflected in the TS. A stronger bond between the nucleophilic atom
and carbon results in a more stable TS and a reduced activation energy.
3. A more electronegative atom binds its electrons more tightly than a less
electronegative one. The S 2 process requires donation of electron density to
N
an antibonding orbital of the reactant, and high electronegativity is unfavorable.
4. Polarizability describes the ease of distortion of the electron density of the
nucleophile. Again, because the S 2 process requires bond formation by an
N
electron pair from the nucleophile, the more easily distorted the attacking atom,
the better its nucleophilicity.
5. A sterically congested nucleophile is less reactive than a less hindered one
because of nonbonded repulsions that develop in the TS. The trigonal bipyra-
midal geometry of the S 2 transition state is sterically more demanding than
N
the tetrahedral reactant so steric interactions increase as the TS is approached.
Empirical measures of nucleophilicity are obtained by comparing relative rates
of reaction of a standard reactant with various nucleophiles. One measure of nucle-
ophilicity is the nucleophilic constant n , originally defined by Swain and Scott. 27
Taking methanolysis of methyl iodide as the standard reaction, they defined n as

n CH 3 I = log k nucl /k CH 3 OH in CH OH 25 C
3
Table 4.3 lists the nucleophilic constants for a number of species according to this
definition.
It is apparent from Table 4.3 that nucleophilicity toward methyl iodide does not
correlate directly with aqueous basicity. Azide ion, phenoxide ion, and bromide are all

25
For general reviews of nucleophilicity see R. F. Hudson, in Chemical Reactivity and Reaction Paths,
G. Klopman, ed., John Wiley & Sons, New York, 1974, Chap. 5; J. M. Harris and S. P. McManus, eds.,
Nucleophilicity, Vol. 215, Advances in Chemistry Series, American Chemical Society, Washington,
DC, 1987.
26 A. Streitwieser, Jr., Solvolytic Displacement Reactions, McGraw-Hill, New York, 1962; J. F. Bunnett,
Annu. Rev. Phys. Chem., 14, 271 (1963).
27
C. G. Swain and C. B. Scott, J. Am. Chem. Soc., 75, 141 (1953).