Rothemund and Adler-Longo reactions revisited: synthesis of tetraphenylporphyrins under equilibrium conditions

We present a new synthetic strategy for preparing tetraphenylporphyrins that should greatly expand synthetic entries into porphyrin containing model systems. Pyrrole and the desired benzaldehyde react reversibly at room temperature with trace acid catalysis to form the cyclic tetraphenylporphyrinogen at thermodynamic equilibrium. An oxidant is then added to irreversibly convert the porphyrinogen to the porphyrin. The greater stability of the cyclic porphyrinogen over the open-chain polypyrrylmethanes occurs when the reaction is performed at moderate dilution (10-2 M). The reaction at high dilution or high concentration affords a negligible yield of the cyclic porphyrinogen. Porphyrinogen exchange reactions provide proof of equilibrium. This methodology is complementary to the Adler-Longo procedure, allowing small quantities of porphyrins to be prepared from sensitive aldehydes in 30-40% yield without difficult purification problems. This methodology is also extended to the preparation of meso-tetraalkylporphyrins and one hybrid porphyrin containing both aryl and alkyl substituents. The mild reaction conditions and convenience of this method permit consideration of new design strategies in preparing complex porphyrins.