Page 414 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

The optimum reactant from a steric point of view is CH –X, because it provides the 395
3
minimum hindrance to approach of the nucleophile. Each replacement of hydrogen
by an alkyl group decreases the rate of reaction. As in the case of the ionization SECTION 4.1
mechanism, the better the leaving group is able to accommodate an electron pair, Mechanisms for
Nucleophilic Substitution
the faster the reaction. Leaving group ability is determined primarily by the C−X
bond strength and secondarily by the relative stability of the anion (see Section 4.2.3).
However, since the nucleophile assists in the departure of the leaving group, the leaving
group effect on rate is less pronounced than in the ionization mechanism.
Two of the key observable characteristics of S 1 and S 2 mechanisms are
N
N
kinetics and stereochemistry. These features provide important evidence for ascer-
taining whether a particular reaction follows an ionization S 1 or direct displacement
N
S 2 mechanism. Both kinds of observations have limits, however. Many nucleophilic
N
substitutions are carried out under conditions in which the nucleophile is present in
large excess. When this is the case, the concentration of the nucleophile is essentially
constant during the reaction and the observed kinetics become pseudo first order.
This is true, for example, when the solvent is the nucleophile (solvolysis). In this
case, the kinetics of the reaction provides no evidence as to whether the S 1orS 2
N
N
mechanism is operating. Stereochemistry also sometimes fails to provide a clear-cut
distinction between the two limiting mechanisms. Many substitutions proceed with
partial inversion of configuration rather than the complete racemization or inversion
implied by the limiting mechanisms. Some reactions exhibit inversion of configu-
ration, but other features of the reaction suggest that an ionization mechanism must
operate. Other systems exhibit “borderline” behavior that makes it difficult to distin-
guish between the ionization and direct displacement mechanism. The reactants most
likely to exhibit borderline behavior are secondary alkyl and primary and secondary
benzylic systems. In the next section, we examine the characteristics of these borderline
systems in more detail.

4.1.3. Detailed Mechanistic Description and Borderline Mechanisms
The ionization and direct displacement mechanisms can be viewed as the limits of
a mechanistic continuum. At the S 1 limit, there is no covalent interaction between the
N
reactant and the nucleophile in the TS for cleavage of the bond to the leaving group.
At the S 2 limit, the bond-formation to the nucleophile is concerted with the bond-
N
breaking step. In between these two limiting cases lies the borderline area in which the
degree of covalent interaction with the nucleophile is intermediate between the two
limiting cases. The concept of ion pairs was introduced by Saul Winstein, who proposed
4
that there are two distinct types of ion pairs involved in substitution reactions. The
role of ion pairs is a crucial factor in detailed interpretation of nucleophilic substitution
mechanisms. 5
Winstein concluded that two intermediates preceding the dissociated carbocation
were required to reconcile data on kinetics and stereochemistry of solvolysis reactions.
The process of ionization initially generates a carbocation and counterion in immediate

4 S. Winstein, E. Clippinger, A. H. Fainberg, R. Heck, and G. C. Robinson, J. Am. Chem. Soc., 78, 328
(1956); S. Winstein, B. Appel, R. Baker, and A. Diaz, Chem. Soc. Spec. Publ., No. 19, 109 (1965).
5
J. M. Harris, Prog. Phys. Org. Chem., 11, 89 (1984); D. J. Raber, J. M. Harris, and P. v. R. Schleyer, in
Ion Pairs, M. Szwarc, ed., John Wiley & Sons, New York, 1974, Chap. 3; T. W. Bentley and P. v. R.
Schleyer, Adv. Phys. Org. Chem., 14, 1 (1977); J. P. Richard, Adv. Carbocation Chem., 1, 121 (1989);
P. E. Dietze, Adv. Carbocation Chem., 2, 179 (1995).