Page 431 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

412 (DMPU), and sulfolane. 30 As a result, the anions are dissociated from the cations,
which enhances their nucleophilicity.
CHAPTER 4
Nucleophilic Substitution O O
HCN(CH ) CH SCH 3 O P[N(CH ) ]
3 2
3 2 3
3
N O N N S
DMF DMSO HMPA H C CH 3 O O
3
CH 3 O
NMP DMPU sulfolane
In the absence of the solvation by protic solvents, the relative nucleophilicity of
anions changes. Hard nucleophiles increase in reactivity more than soft nucleophiles.
As a result, the relative reactivity order changes. In methanol, for example, the relative
−
−
−
−
−
−
reactivity order is N > I > CN > Br > Cl . In DMSO the order becomes CN >
3
− 31
−
−
−
N > Cl > Br > I . The reactivity order in methanol is dominated by solvation
3
and the more weakly solvated N − and I − ions are the most reactive nucleophiles.
3
The iodide ion is large and very polarizable. The anionic charge on the azide ion is
dispersed by delocalization. When the effect of solvation is diminished in DMSO,
other factors become more important, including the strength of the bond being formed,
which accounts for the reversed order of the halides in the two series. There is also
evidence that S 2 TSs are better solvated in aprotic dipolar solvents than in protic
N
solvents.
In interpreting many aspects of substitution reactions, particularly solvolysis, it
is important to be able to characterize the nucleophilicity of the solvent. Assessment
of solvent nucleophilicity can be done by comparing rates of a standard substitution
process in various solvents. One such procedure is based on the Winstein-Grunwald
32
equation :
log k/k = lN +mY
0
where N and Y are measures of the solvent nucleophilicity and ionizing power, respec-
tively. The variable parameters l and m are characteristic of specific reactions. The
value of N, the indicator of solvent nucleophilicity, can be determined by specifying
a standard reactant for which l is assigned the value 1.00 and a standard solvent
for which N is assigned the value 0.00. The parameters were originally assigned
for solvolysis of t-butyl chloride. The scale has also been assigned for 2-adamantyl
tosylate, in which nucleophilic participation of the solvent is considered to be negli-
gible. Ethanol-water in the ratio 80:20 is taken as the standard solvent. The resulting
solvent characteristics are called N Tos and Y Tos . Some representative values for solvents
that are frequently used in solvolysis studies are given in Table 4.5. We see that
nucleophilicity decreases from ethanol to water to trifluoroethanol to trifluoroacetic
acid as the substituent becomes successively more electron withdrawing. Note that
the considerable difference between acetic acid and formic acid appears entirely in

30
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32
S. Winstein, E. Grunwald, and H. W. Jones, J. Am. Chem. Soc., 73, 2700 (1951); F. L. Schadt,
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