Abstract
A convenient synthesis of α-(n -alkylcarbonyloxy)alkyl (ACOA) iodides has been developed and a homologous series
of n -alkylcarbonyloxymethyl (ACOM) iodides have been used to alkylate 4-hydroxyacetanilide
(acetaminophen, APAP), a sterically unhindered phenol, and a sterically hindered phenol
(2,2,5,7,8-pentamethyl-6-chromanol). Steric hindrance was not a significant factor
in the ratio of acylated (Path b) to alkylated (Path a) for these reactions. Given
the reported toxicity associated with sterically hindered ACOM prodrugs, n -alkyl ACOM and ACOA promoieties present themselves as viable alternatives to the
more commonly used pivalate-based derivatives.
Key words
acylation - alkyl halides - alkylation - phenols - steric hindrance
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