Morphine contains two alcohol groups, one phenolic and the other allylic. Acetylation of both alcohols provides the illegal street drug heroin. The selective acetylation of either alcohol has also been reported. We have determined that these conditions provide the same selectivity as observed for morphine with molecules lacking the structural complexity of morphine. Specifically, 1:1 mixtures of phenol and 2-cyclohexen-1-ol, when reacted with aqueous sodium bicarbonate and acetic anhydride, provided exclusively the acetylated phenol. Likewise, reaction of 1:1 mixtures of phenol and 2-cyclohexen-1-ol with acetic acid and catalytic sulfuric acid provided exclusively the acetylated allylic alcohol. We have further investigated the cause for the selectivity under the basic conditions by attempting to determine the mechanism by which phenols are acetylated. The selectivity mentioned above strongly suggests that the phenolic hydroxyl group is deprotonated prior to nucleophilic attack on the acetic anhydride, despite sodium bicarbonate being too weak to perform the deprotonation. Kinetic experiments have shown that the reaction rate is dependent upon pH, not the concentration of base, thereby clarifying the conundrum. The phenolic hydroxyl group reacts more rapidly under the weakly basic conditions than the allylic hydroxyl group because it is deprotonated by hydroxide prior to nucleophilic attack on acetic anhydride. The role of the base, sodium bicarbonate, is to increase the pH of the solution, thereby increasing the concentration of hydroxide ion.
Back to Undergraduate Posters I
Back to The 56th Southeast Regional Meeting 2004 (November 10-13, 2004)