Applications of HSAB Theory

In an attempt to predict product distributions, HSAB theory, has been applied to many chemical reactions not usually classified as acid-base reactions. Care should be exercised in nontrivial cases but this approach may be of value in predicting the likelihood of a number of reactions in a synthetic plan. Several examples are illustrated below. O 

Substitution (also see sec. 2.7). Saville showed that nucleophilic displacement of alkyl halides can be characterized by HSAB theory.In general, the reaction works best when the R group and nucleophile partner are matched. The two major categories are 

When R—C has a greater differential in hardness and softness, the reaction proceeds best. Table 2.7 shows that chloromethane is harder than iodomethane. Therefore, a hard base such as methoxide will show a larger energy difference for iodomethane, which should react faster. 

Epoxidation. Peroxyacids such as 30 (sec. 3.4.C) contain an unusual soft-hard combination that i leads to attack by a soft alkene (a soft base) on the soft oxygen of the peroxyacid. 

Carbonyls. The carbon of a carbonyl is a hard acceptor and the oxygen is a hard donor. 

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Acid-base properties of solids are usually discussed, mostly, in terms of Lewis and Brpnsted definitions of acidity and basicity, but interesting applications of HSAB theory to solid-gas interfaces can be found in Reference 15 and Reference 16. 

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