Complete in Situ Activation of Carboxylic Acids

As can be seen from Table 6.1, a number of mixed anhydrides are good acylating agents. Some mixed anhydrides are commercially available. However, most such acylating agents are prepared in situ from the carboxylic acid and a suitable reagent. Four of these mixed anhydrides will be discussed in more detail in the following. 

Poor nucleophiles react with acyl isoureas B so slowly that the latter start to decompose. In some sense they acylate themselves. The N atom designated with the positional number 3 intramolecularly substitutes the O-bound leaving group that is attached to the carboxyl carbon Cl. A four-membered cyclic tetrahedral intermediate is formed. When the Cl -Ol bond in this intermediate opens up, the N-acyl urea E is produced. Because compound E is an amide derivative it is no longer an acylating agent (cf. Section 6.2). 

In situ Activation of a Carboxylic Acid through 0-Silylation 

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