Rapid base-catalyzed deuterium exchange at the ring-adjacent methyl and methylene positions of octaalkyl and natural-derivative porphyrins and metalloporphyrins

An extremely rapid, simple, and inexpensive method is reported for preparation of ring methyl and methylene deuteriated porphyrins and metalloporphyrins. Base-catalyzed ring methyl deuteriation is accomplished at room temperature in an inert atmosphere by the addition of the porphyrin derivative and base to dimethyl-d6 sulfoxide (Me2SO). The ring methyl groups of the iron(III) complexes of etioporphyrin, protoporphyrin IX, deuteroporphyrin IX, and mesoporphyrin IX were at least 74% and in most cases > 95% deuteriated in 24 h, with minimal (< 5%) porphyrin degradation. The dimethyl ester complexes of the natural-derivative porphyrin complexes also underwent facile deuterium exchange, but the porphyrins were quickly de-esterified in the basic solution. Either tetrabutylammonium hydroxide (1 M in methanol) or potassium tert-butoxide served as the base. When tetrabutylammonium hydroxide ((TBA)OH) was used as the base, the amount of methanol present in solution was found to be important. Some methanol is presumably required to solvate the hydroxide ion. Both the iron(III) and manganese(III) etioporphyrin I chloride complexes were deuteriated at the ring-adjacent positions by this method. More rigorous conditions were needed to deuteriate the ring methylene positions of octaalkylporphyrins. The ring methylene positions of free-base octaethylporphyrin (H2OEP) were exchanged in refluxing Me2SO-d6 under a nitrogen atmosphere. After a 24-h reflux, 50% of the H2OEP was recovered and was found to be at least 95% deuteriated at the ring methylene positions. No significant methine or β-methyl deuteriation (< 5%) had occurred. 24 references, 2 figures, 2 tables