Page 429 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

−
410 able to predict whether a chemical species Y will act as a nucleophile or as a base
under a given set of conditions. Scheme 4.3 lists some examples.
CHAPTER 4 Basicity is a measure of the ability of a substance to attract protons and refers to
Nucleophilic Substitution an equilibrium with respect to a proton transfer from solvent:

+
B +H O B H+ OH
−
2
These equilibrium constants provide a measure of thermodynamic basicity, but we also
need to have some concept of kinetic basicity. For the reactions in Scheme 4.3, for
example, it is important to be able to generalize about the rates of competing reactions.
The most useful qualitative approach for making predictions is the hard-soft-acid-base
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(HSAB) concept (see Section 1.1.6), which proposes that reactions occur most readily
between species that are matched in hardness and softness. Hard nucleophiles prefer
hard electrophiles, whereas soft nucleophiles prefer soft electrophiles.
The HSAB concept can be applied to the problem of competition between nucle-
ophilic substitution and deprotonation as well as to the reaction of anions with alkyl
3
halides. The sp carbon is a soft electrophile, whereas the proton is a hard electrophile.
Thus, according to HSAB theory, a soft anion will act primarily as a nucleophile,
giving the substitution product, whereas a hard anion is more likely to remove a proton,
giving the elimination product. Softness correlates with high polarizability and low
electronegativity. The soft nucleophile–soft electrophile combination is associated with
a late TS, where the strength of the newly forming bond contributes significantly to the
structure and stability of the TS. Species in Table 4.3 that exhibit high nucleophilicity
toward methyl iodide include CN ,I , and C H S . These are soft species. Hardness
−
−
−
6 5
Scheme 4.3. Examples of Competition between Nucleophilicity and Basicity
–
+
–
S 1 Substitution Y: acts as a nucleophile Y: +R C CHR' 2 R CCHR' 2
N
2
2
versus Y
+
E1 Elimination Y: acts as a base Y: +R C CHR' 2 R C CR' 2 + H Y
–
–
2
2
2 Substitution – – –
S N Y: acts as a nucleophile Y: + RCH CH X RCH CH Y +X
2
2
2
2
versus
E2 Elimination Y: acts as a base Y: – + RCH CH X RCH CH 2 + H Y
2
2
–
O O –
–
Nucleophilic addition Y: acts as a nucleophile Y: – + RCH CR' RCH 2 CR'
2
to a carbonyl group
Y
O O –
–
Enolate formation Y: acts as a base Y: – + RCH CR' RCH CR' + H Y
2
28
R. G. Pearson and J. Songstad, J. Am. Chem. Soc., 89, 1827 (1967); R. G. Pearson, J. Chem. Ed., 45,
581, 643 (1968); T. L. Ho, Chem. Rev., 75, 1 (1975).