Beneficial effects of salts on an acid-catalyzed condensation leading to porphyrin formation

Article abstract of DOI:10.1016/S0040-4020(97)00770-9

Addition of one of a variety of salts to the room temperature, two-step, one flask reaction at 0.1 M forming tetraphenylporphyrin (TPP) gave yield increases of up to 2-fold. Among 21 insoluble salts, 12 gave increased yields, 6 had no effect, and 3 gave diminished yields. The salts that gave increases encompassed diverse cations but were restricted to the anions Cl^-, Br^-, I^-, and Ph₄B^- while SO₄^2-, F^-, or BF₄^- did not give improved yields. All 7 soluble tetraalkylammonium or tetraphenylphosphonium salts (F^-, Cl^-, Ph₄B^-, PF₆^-, or HSO₄^- counterions) that were surveyed gave yield increases of > 1.5 fold. Thus a 10^-1 M pyrrole-benzaldehyde condensation catalyzed with 10^-2 M BF₃·O(Et)₂ in CH₂Cl₂ containing 0.1 equiv of NaCl (5.85 mg/10 mL CH₂Cl₂) or 0.0031 equiv of benzyltributylammonium chloride (Bu₃BzlNCl) (based on [benzaldehyde]) gave ~50% yield compared with ~25% in the reaction without salt. The pyrrole-aldehyde condensation is much faster in the presence of salt, as measured by the rate of disappearance of benzaldehyde and the rate of formation of the porphyrin. Yield increases in the presence of salt were observed with catalysis by BF₃·O(Et)₂, BF₃·2H₂O, and CF₃CO₂H. Significant salt effects also were observed with BF₃·O(Et)₂ or CF₃CO₂H in the solvent diethyl ether, but the maximum yield was 15%. A survey of nine aldehydes showed yield improvements of up to 2-fold in six cases in the presence of salt. During the pyrrole-aldehyde reaction in CH₂Cl₂ either in the presence or absence of soluble salts, the medium becomes heterogeneous (measured by nephelometry). The addition of water to BF₃·O(Et)₂ in CH₂Cl₂ also yields a heterogeneous medium; in the presence of salt this medium affords twice the yield of porphyrin as that formed in the absence of salt. ¹¹B NMR and ¹⁹F NMR experiments failed to unveil any new species formed by interaction of chloride-containing salts with BF₃·O(Et)₂. The complexity of the reaction medium, as well as insufficient information about the nature of the pyrrole-aldehyde condensation, preclude an assignment of mechanisms underlying the salt effects. However, a rank ordering of salts in the porphyrin reaction does not correlate with their desiccative power, and the generality of the salt effects is at odds with the selective anion templating of tetrapyrrolic macrocycles. Irreversible features of the pyrrole-aldehyde condensation have been identified via exchange experiments during the course of the reaction and ¹³C NMR labeling experiments. The improved reaction conditions can be used for preparative-scale syntheses, as 720 mg tetra(nphenylporphyrin (47% yield) was obtained from a 100 mL-scale reaction with 0.1 M reactants at room temperature.