Page 336 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

falling in the range 75–80 kcal, which is weaker than either allylic or benzylic bonds. 317
Because of the prevalence of such bonds in peptides and proteins, the strength of the
C−H bonds of -amido carboxamides is of substantial biological interest. 104 SECTION 3.4
The stabilization provided by various functional groups contributes to reduced Electronic Substituent
Effects on Reaction
BDEs for bonds to the stabilized radical center. Computational methods can be used Intermediates
to assess these effects. The BDE can be calculated by comparing the total energy of
the dissociated radicals with the reactant. Differences in bond dissociation energies
relative to methane ( BDE) can be taken as a measure of the stabilizing effect of the
substituent on the radical. Some computed BDE values are given in Table 3.19 and
compared with experimental values. As an example of the substituent effect on BDEs,
it can be seen that the primary C−H bonds in acetonitrile (12 kcal/mol) and acetone
(11 kcal/mol) are significantly weaker than a primary C−H bond in methane. The data
show that both electron-releasing and electron-withdrawing functional groups stabilize
radicals. The strong bond-weakening effect of amino substituents is noteworthy, both
in its size and the apparent underestimation of this effect by the computations. A recent
reevaluation of the BDE for amines arrived at a value of 13±1kcal/mol, which is
in better agreement with the calculations. 102b
Theoretical calculations on radical stability entail some issues that are not present
in diamagnetic molecules. These complications originate from the need to account
for the singly occupied orbital. A comparison assessed the ability of a range of
computational methods to reproduce radical stabilization energies. 105 A variant of the
CBS-Q method called CBS-RAD was found adequate for calculation of geometry and
energy of the FCH ·,CH =CF·, and NCCH · radicals. This method, along with others,
2 2 2

Table 3.19. Substituent Stabilization Relative to the Methyl Radical (in
kcal/mol)
Substituent BDE a AUMP2 b B3LYP/6-31+G c G3(MP2)RAD d CBS-RAD d
H 0 0 0 0 0 0 0 0 0 0
7 3 2 4 8 3 4 3 8
CH 3
CH 2 =CH 19 12 6 18 8 16 9 17 6
17
C 6 H 5
HC=O 9 5 8 3 9 6
CH 3 C=O 11 9 2
C 6 H 5 C=O 12
10 5 1 6 0
CO 2 C 2 H 5
CN 12 6 7 10 4 7 6 8 9
7 2 8 3 3
NO 2
F 3 5 0 3 0 3 3
CH 3 O 12 8 9 OH 9 8 7 4 8 2
22 11 1 13 3 10 6 11 6
NH 2
CH 3 2 N 21
a. F. G. Bordwell, X. -M. Zhang, and M. S. Alnajjar, J.Am.Chem.Soc., 114, 7623 (1992); F. G. Bordwell
and X. -M. Zhang, Acc.Chem.Res., 26, 570 (1993).
b. M. Lehd and F. Jensen, J. Org. Chem., 56, 884 (1991).
c. B. S. Jursic, J. W. Timberlake, and P. S. Engel, Tetrahedron Lett., 37, 6473 (1996).
d. D. J. Henry, C. J. Parkinson, P. M. Mayer, and L. Radom, J. Phys. Chem. A, 105, 6750 (2001).

104 P. E. M. Siegbahn, M. R. A. Blomberg, and R. H. Crabtree, Theoretical Chem. Acc., 97, 289 (1997);
P. A. Frey, Annu. Rev. Biochem., 70, 121 (2001); G. Sawyers, FEMS Microbiological Rev., 22, 543
(1998).
105
P. M. Mayer, C. J. Parkinson, D. M. Smith, and L. Radom, J. Chem. Phys., 108, 604 (1998).