Hydroxycarboxylic adds, lactonization

For work on a 1-mole scale one would thus have to use a 1000-liter flask to activate and then lactonize the entire w-hydroxycarboxylic add at once. Of course, it is much more practical to work in a smaller reaction vessel. However, there one must also not exceed the mentioned concentration limit of <1 /xmol/L. Therefore, one can introduce only as much of the carboxylic add in this smaller reaction vessel at a time so that its concentration does not exceed 1 /xmol/L. Subsequently, one would have to activate this amount of acid and would then have to wait until it is lactonized. After that additional acid would have to be added and then activated, and so on. A more practical alternative is shown in Side Note 6.1. 

TABLE 5.12. Some Hydroxycarboxylic Adds and the Lactones Which May Be Derived from Them... 

The discontinuous process for preparing macrolactones described in the text is impractical. Instead of this process one uses a continuous method with a syringe pump one adds a solution of the hydroxycarboxylic acid very slowly—that is, in the course of hours or days—into a small flask, which contains >1 equivalent of the activator and, if necessary, just enough triethylamine to neutralize any released HCl.The rate at which the acid is added is regulated such that it is equal to or smaller than the lactonization rate. This procedure is called working under pseudo-high dilution. At the end of the... 

Generally, lactones with five-membered and six-membered rings are not too reactive. They are relatively stable in acidic solutions, where they typically arise by spontaneous dehydration of hydrox-ycarboxylic adds. In aqueous solutions, particularly in alkaline solutions, the lactone ring opens with the formation of a salt of the hydroxycarboxylic acid. The original lactone may result after acidification, especially on heating. Lactones react with alcohols to form esters and, similarly, the lactone ring opens on reaction with amino compounds to form amides. 

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