Surprising Outcomes of Classic Ring Expansion Conditions Applied to Octaethyloxochlorin. 3. Schmidt Reaction Conditions

The Schmidt reaction (treatment of a ketone with sodium azide and a mineral acid) is an alternative to the Beckmann rearrangement to expand a cyclic ketone to a lactam. However, this approach toward the conversion of a synthetic porphyrin to a derivative containing a non-pyrrolic building block failed to generate the expected lactam. Instead, using sulfuric acid as a catalyst, a novel heptaethyl-2-hydroxy-chlorin-3-one was formed, structurally characterized, and its mechanism of formation deduced. The work demonstrates how the extraordinary structural stability of the porphyrin macrocycle redirects the reactivity of classic ring expansion reactions. Using hydrochloric acid as a catalyst, a somewhat regioselective chlorination of the meso-positions of the oxochlorin was observed. The halogenation sites were determined spectroscopically and by X-ray crystallography of select derivatives. The regioselectivity of the halogenation was computationally rationalized. This method to generate regioselectively 5-chloro-, 10-chloro-, and 5,10-dichloro-oxochlorins is superior over alternative halogenation methods.

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