Hard-Soft Acid-Base(HSAB) theory one of the most useful rules of thumb for explaining and predicting chemical reactivity trends. Hard molecules tend to be small/non-polarizable and charged while soft molecules tend to be large/polarizable and uncharged. Both acids/electrophiles and bases/nucleophiles can be hard and soft and the defining reactivity rule of HSAB theory is:
- hard acids prefer to react with hard bases forming ionic bonds
- soft acids prefer to react with soft bases forming covalent bonds
These rules are especially useful for rationalizing regioselectivity in ambident molecules (molecules that have more than one reactive site) such as enols and enones (see figure above):
- hard acids react with the oxygen of the enolate
- soft acids react with the carbon of the enolate
- hard bases react with the carbonyl carbon of the enone
- soft bases react with the β-carbon of the enone
KLOPMAN EQUATION EXPLAINS HSAB THEORY:
Finally, though these rules were originally derived empirically, there is quantum mechanical explanation for these trends in the Klopman equation:
This equation shows how chemical reactivity is defined by two terms: (1) an electrostatics (ionic) term and (2) orbital (covalent) term. In general:
- hard/hard interactions maximize the electrostatic term (i.e. highly charged molecules are very attracted to each other)
- soft/soft interaction maximize the orbital overlap term (i.e. molecules with similar energy HOMO’s and LUMO’s most easily make covalent bonds)
- Pearson, R.G. Hard and Soft Acids and Bases. J. Am. Chem. Soc. 1963, 85, 3533-3539.
- Pearson, R.G.; Songstad,J. Application of the Principle of Hard and Soft Acids and Bases to Organic Chemistry J. Am. Chem. Soc. 1966, 89, 1827-1836.
- Klopman, G. Chemical Reactivity and the Concept of Charge- and Frontier-Controlled Reactions. J. Am. Chem. Soc. 1968, 90, 223-234.
- Pearson, R.G. Hard and Soft Acids and Bases, HSAB, Part II. J. Chem. Educ. 1968, 45, 643-648.
- Fleming, I. Frontier Orbitals and Organic Chemical Reactions, Wiley-Interscience, 2004
- McQuarrie, D.A.; Simon, J.D. Physical Chemistry: A Molecular Approach. University Science Books, 1997
- Carey, F.A.; Sundberg, R.J. Advanced Organic Chemistry, Part A: Structure and Mechanisms. Springer 2008
This work by Eugene Douglass and Chad Miller is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.