Page 339 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

320 Substituents with unshared electrons allow electron delocalization, which stabi-
lizes the compound and increases the negative charge on oxygen. This resonance
CHAPTER 3
effect stabilizes the carbonyl compound and decreases the reactivity of the carbonyl
Structural Effects on group toward nucleophiles. The order of electron donation by resonance is RN >
−
Stability and Reactivity
−
O > NR > OR ∼ OH > F. The trends in the resonance and polar effects of these
2
substituents are reinforcing and lead to the overall reactivity trends shown above. The
amido group is the strongest resonance donor and weakest polar acceptor, whereas the
fluorine is the weakest donor and strongest acceptor.
There have been several attempts to analyze these substituent effects using compu-
tational approaches. For example, the isodesmic reaction
O O
R C X + CH 3 CH 3 R C CH 3 + CH 3 X

yields the results shown in Table 3.21. 106 In this formulation, the total stabilization
includes both the differences between the C−X and the C−C bond strength and the
resonance stabilization of the substituent. Remember (Section 3.1.2.2) that the C−X
bond strength increases because of electronegativity differences. An indication of the
extent of the conjugation can be obtained from the C−X bond orders shown in
Figure 3.20. The C=X bond order decreases in the series NH 0 28 > OCH 0 22 >
+
3
2
F 0 13 . These values can be contrasted to those for C≡N and CH , where there is
3
minimal delocalization and the bond orders are around 0.04. Figure 3.20 also
shows the atomic charges, as determined by the AIM method.
It is also desirable to separate the resonance component of the total stabilization
energy. Wiberg addressed the issue by comparing total stabilization with the rotational
barrier, which should be a measure of the resonance contribution. 107 The resonance
component for F was assumed to be zero. This analysis provides the order NH > OH
2
for the stabilization but OH > NH for the component, as shown in Table 3.22.
2

Table 3.21. Carbonyl Substituent Stabilization as Estimated by Isodesmic
Replacement by Methyl (in kcal/mol) a
Substituent H exp HF/6-31G ∗ MP2/6-31G ∗ MP3/6-311++G ∗∗
19 6 20 6 21 2 18 3
NH 2
OH 23 4 25 5 26 8 22 3
F 17 9 19 0 21 1 16 4
−13 0 −12 0 −12 6
SiH 3
−6 2 −3 5 −3 9
PH 2
SH 4 5 4 3 7 3 5 5
Cl 6 6 2 9 7 9 6 7
CN −11 8 −9 3 −11 0
−11 9 −11 0 −12 4
CF 3
a. Data from K. B. Wiberg, C. M. Hadad, P. R. Rablen, and J. Cioslowski, J. Am. Chem. Soc., 114, 8644
(1992).

106 K. B. Wiberg, C. M. Hadad, P. R. Rablen, and J. Cioslowski, J. Am. Chem. Soc., 114, 8644 (1992).
107
K. B. Wiberg, Acc. Chem. Res., 32, 922 (1999); K. B. Wiberg, J. Chem. Educ., 73, 1089 (1996).