Investigating Steric Effects in SN2 Substitution Reactions

The experimental procedure for the preparation of phenacetin, by the reaction of acetaminophen with ethyl iodide, has been modified to use several different alkyl halides, and to allow for easier isolation of the substitution products. The isolated student yields of substitution products are 65–75% for normal primary alkyl bromides, 40–50% for 2-bromopropane and 2-bromobutane, and no isolated product using t-butyl chloride. These results are what might be expected for an SN2 reaction, due to increasing steric hindrance to backside attack. Isobutyl bromide and cyclohexyl bromide each yield lower amounts of substitution products (10–15% and 3–4%, respectively) than might be expected, which allows students to consider subtler factors which can influence the yield of product.