Stereopopulation Control. 9. Rate and Equilibrium Enhancement in the Lactonization of (o-Hydroxyphenyl)acetic Acids

Article abstract of DOI:10.1021/jo00168a018

The kinetics of lactonization of (2,4-dimethyl-6-hydroxyphenyl)dimethylacetic acid have been investigated over the pH range 2.2-11.8 in unbuffered aqueous solution (30 degC, 20percent dioxane).Concurrent catalysis by both forms of imidazole buffer has also been demonstrated.The rate constant for specific acid catalysis of lactonization (17.8 M^-1s^-1) is 2 * 10E7 times as great as that for the parent compound, (o-hydroxyphenyl)acetic acid; a comparable enhancement factor is found for specific base catalysis.The equilibrium content of lactone is >99percent at all pH values below 10.5; in more alkaline media, phenol ionization stabilizes the dianion form of the phenolic acid.The introduction of methyl groups (α-, α-, and 2-positions) is equally effective in enhancing formation of the five-membered fused lactone as in the case of the analogous six-membered lactone.