1. Mechanism of the Schmidt Reaction Jennifer Poutsma, Department of Chemistry & Biochemistry, Old Dominion University
The utility of the Schmidt reaction was long thought to be limited to the use of hydrazoic acid, as early work on the Schmidt reaction showed that no product or very little product was obtained when alkyl azides were employed. This observation seems to indicate that the parent reaction follows path b instead of path a (Figure 1). However, in the early 1990’s, an intramolecular version of this reaction was found to give high yields with the use of an appropriate Lewis acid. Presumably, this reaction goes through path a. It is unclear why having the alkyl group intramolecular should now make path a more likely. Another possibility is that alkyl azides are not nucleophilic enough to attack the activated carbonyl, but the more favorable entropy of the intramolecular attack lowers the free energy enough to make this reaction feasible.
Calculations on an intramolecular reaction (Figure 3) give a 0.4 kcal/mol energy barrier for azide attack and 8.3 kcal/mol for migration. The corresponding calculations on an alkyl azide intermolecular reaction give an azide attack barrier of 0.8 kcal/mol and a migration barrier of 11 kcal/mol (Figure 4). Thus, intermolecular versus intramolecular does not seem to have an effect on the energetics. Presumably, when the entropy is included the intermolecular reaction will have a higher barrier than the intramolecular version. However, the barrier is so small that it seems unlikely that the entropy will be large enough to make the intermolecular reaction energetically unfeasible.