Carboxylates acetylation with ketene

The slow acetylation of the hydroxyl group is difficult to explain. One is inclined to suggest that this group is coordinated to the metal ion and consequently rendered inactive. Such a possibility requires either a coordination number of 7 for chromium (III) or displacement of carboxylate from the coordination sphere by hydroxyl. In the latter instance an uncoordinated functional group would still be present to react with ketene (COO or COOH) and anhydride should be detected in the crude reaction product. This is not the case. 

Acylation. Reaction conditions employed to acylate an aminophenol (using acetic anhydride in alkaU or pyridine, acetyl chloride and pyridine in toluene, or ketene in ethanol) usually lead to involvement of the amino function. If an excess of reagent is used, however, especially with 2-aminophenol, 0,A/-diacylated products are formed. Aminophenol carboxylates (0-acylated aminophenols) normally are prepared by the reduction of the corresponding nitrophenyl carboxylates, which is of particular importance with the 4-aminophenol derivatives. A migration of the acyl group from the O to the N position is known to occur for some 2- and 4-aminophenol acylated products. Whereas ethyl 4-aminophenyl carbonate is relatively stable in dilute acid, the 2-derivative has been shown to rearrange slowly to give ethyl 2-hydroxyphenyl carbamate [35580-89-3] (26). 

Esterification of resin-bound alcohols with 3-oxo carboxylic acids (which readily undergo decarboxylation) or with malonic acid is best performed using the corresponding ketenes, which can be generated in situ by thermolysis of dioxinones or other precursors (Entries 6-9, Table 13.12). PEG can also be acetoacetylated with acetyl ketene generated by thermolysis [171]. 

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