Page 288 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

the semiempirical calculations are much faster in terms of computer time. The time 269
requirement for an ab initio calculation increases rapidly as the number of atoms in the
molecule increases. The C hydrocarbons represent the current practical limit for high- SECTION 3.1
8
level ab initio computations. DFT computations are faster than ab initio computations Thermodynamic Stability
and the amount of computer time required does not increase as rapidly with molecular
size. The choice of basis set orbitals influences the outcome, and often several basis
sets are checked to determine which are adequate. A choice of computational method
is normally made on the basis of evidence that the method is suitable for the problem at
hand and the availability of appropriate computer programs and machine time. Results
should be subjected to critical evaluation by comparison with experimental data or
checked by representative calculations using higher-level methods.

3.1.2.6. Limitations on Enthalpy Data for Predicting Reactivity. Whether H for a
projected reaction is based on tabulated thermochemical data, bond energy, equivalent
group additivity, or on MO or DFT computations, fundamental issues that prevent a
final conclusion about a reaction’s feasibility remain. In the first place, most reactions
of interest occur in solution, and the enthalpy, entropy, and free energy associated
with any reaction depend strongly on the solvent medium. There is only a limited
amount of tabulated thermochemical data that are directly suitable for the treatment
of reactions in organic solvents. 40 MO and DFT calculations usually refer to the
isolated (gas phase) molecule. Estimates of solvation effects on reactants, products,
intermediates, and transition states must be made in order to apply either experimental
or computational thermochemical data to reactions occurring in solution. There may
be substantial differences between solvation energies of reactants, transition states,
intermediates, and products. If so, these solvation differences become a major factor
in determining reactivity.
An even more fundamental limitation is that H data give no information about
the rate of a chemical reaction. It is the energy of the transition state relative to the
reactants that determines the reaction rate. To be in a position to make judgments
on reactivity, we have to see how structure is related to reactivity. To do this, we
need information about the energy of transition states and intermediates, but because
transition states are transitory, we have no physical means of determining their
structure. We can, however, determine their energy relative to reactants on the basis
of reaction kinetics. We address this topic in the next sections by first examining the
principles of chemical kinetics. We can also obtain information about transition states
and intermediates by studying the effect of substituents on the rate of reaction. In
Section 3.4, we look at how key intermediates such as carbocations, carbanions, and
radicals respond to substituents.
Theoretical descriptions of molecules have been applied to the structure of
transition states and unobservable intermediates. By applying MO or DFT methods,
structures can be calculated for successive geometries that gradually transform the
reactants into products. Exploration of a range of potential geometries and calcu-
lation of the energy of the resulting ensembles can, in principle, locate and describe

J. Am. Chem. Soc., 107, 3902 (1985); J. N. Levine, Quantum Chemistry, 3rd Edition, Allyn and Bacon,
1983, pp. 507–512; W. Hehre, L. Radom, P. v. R. Schleyer, and J. A. Pople, Ab Initio Molecular Orbital
Calculations, John Wiley & Sons, 1986, Chap. 6; B. H. Besler, K. M. Merz, Jr., and P. Kollman,
J. Comput. Chem., 11, 431 (1990); M. Sana and M. T. Nguyen, Chem. Phys. Lett., 196, 390 (1992).
40
Guthrie has explored the use of a group equivalent scheme to compute G f for aqueous solutions.
J. P. Guthrie, Can. J. Chem., 70, 1042 (1992).