Page 437 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

418 Table 4.10. Substituent Effects of
-EWG Substituents a

CHAPTER 4 ZCH 2 Cl + I – ZCH 2 I
Nucleophilic Substitution
Z Relative rate Z Relative rate

CH CH CH 2 1 PhC O 3.2 × 10 4
3
2
PhSO 2 0.25 N C 3 × 10 3
H OC
CH C O 3.5 × 10 4 C 2 5 O 1.7 × 10 3
3
a. F. G. Bordwell and W. T. Branner, Jr., J. Am. Chem. Soc., 86, 4645 (1964).

Adjacent carbonyl groups also affect reactivity. Substitution by the ionization
mechanism proceeds slowly on
-halo derivatives of ketones, aldehydes, acids, esters,
nitriles, and related compounds. As discussed on p. 304, such substituents destabilize
a carbocation intermediate, but substitution by the direct displacement mechanism
proceeds especially readily in these systems. Table 4.10 indicates some representative
relative rate accelerations.
Steric effects may be responsible for part of the observed acceleration, since an
2
sp carbon, such as in a carbonyl group, offers less steric resistance to the incoming
nucleophile than an alkyl group. The major effect is believed to be electronic. The
adjacent LUMO of the carbonyl group can interact with the electron density that
builds up at the pentacoordinate carbon in the TS. This can be described in resonance
terminology as a contribution from an enolate-like structure to the TS. In MO termi-
nology, the low-lying LUMO has a stabilizing interaction with the developing p orbital
of the TS (see p. 394 for MO representations of the S 2 transition state). 49
N

Nu Nu LUMO
– O – O
HOMO

X X
resonance representation of MO representation of stabilization
electronic interaction with carbonyl of substitution transition state through
group and substitution center interaction with C O π* orbital
to delocalize negative charge

It should be noted that not all electron-attracting groups enhance reactivity. The
sulfonyl and trifluoro groups, which cannot participate in this type of conjugation,
retard the rate of S 2 substitution at an adjacent carbon. 50
N
The extent of the rate enhancement of adjacent substituents is dependent on the
nature of the TS. The most important factor is the nature of the -type orbital that
develops at the trigonal bipyramidal carbon in the TS. If the carbon is cationic in
character, electron donation from adjacent substituents becomes stabilizing. If bond
formation at the TS is advanced, resulting in charge buildup at carbon, electron

49 R. D. Bach, B. A. Coddens, and G. J. Wolber, J. Org. Chem., 51, 1030 (1986); F. Carrion and
M. J. S. Dewar, J. Am. Chem. Soc., 106, 3531 (1984); S. S. Shaik, J. Am. Chem. Soc., 105, 4359 (1983);
D. McLennon and A. Pross, J. Chem. Soc., Perkin Trans., 2, 981 (1984); T. I. Yousaf and E. S. Lewis,
J. Am. Chem. Soc., 109, 6137 (1987).
50
F. G. Bordwell and W. T. Brannen, J. Am. Chem. Soc., 86, 4645 (1964).