Porphyrins have been known to undergo diprotonation to form porphyrin diacids (diprotonated porphyrins) under acidic conditions without forming porphyrin monoacids (monoprotonated porphyrins). So far, chemistry of monoprotonated porphyrins has not yet to be sufficiently pursued due to the difficulty of the formation. It should be required to establish a solid preparation procedure of monoprotonated porphyrins in solution and in solid for the development of supramolecular assemblies based on monoprotonated porphyrins. Previously, saddle-distorted dodecaphenylporphyrin (H₂DPP) allowed us to observe stepwise protonation in benzonitrile and isolation of monoprotonated H₃DPP⁺ with use of 2-anthrathene sulfonic acid (2-AnSO₃H) as a hydrogen-bonded supramolecular assembly, [H₃DPP](2-AnSO₃)(CH₃OH), which was obtained by crystallization from dichloromethane/CH₃OH [1].

In order to establish the requirements for the formation of monoprotonated porphyrin, we examined reactions of H₂DPP with carboxylic acids, including trifluoroacetic acid (TFA), in acetone in the presence of methanol. In the course of titration of H₂DPP using TFA in a mixture of acetone/methanol (3%), we could observe two-step spectral change showing different isosbestic points, indicating step-wise protonation of H₂DPP. Upon addition of 1 eq of TFA to the solution of H₂DPP in acetone-d₆/methanol-d₄ (3%), the ¹H NMR spectrum of the mixture allowed us to observe signals assigned to the o-protons of the meso-phenyl groups of H₃DPP⁺ at 8.1 ppm, those of H₂DPP and H₄DPP²⁺ at 7.7 and 8.3 ppm, respectively. We found that the amount of methanol added had a great impact on the yield of the monoacid relative to the initial concentration of H₂DPP: The increase of the portion of methanol up to 10% gained the yield, reaching to 90%. These results indicate that the formation of monoprotonated porphyrin selectively occurs in the presence of a protic solvent such as methanol even using TFA, which affords only diprotonated species in acetone.

   The importance of methanol for the formation of H₃DPP⁺ was demonstrated by the crystal structure of [H₃DPP](CF₃COO)(MeOH). As depicted in Figure 1, the crystal structure involves hydrogen bonding of both a methanol molecule and CF₃COO^– with H₃DPP⁺. Thus, together with the impact of the amount of methanol on the formation yield of H₃DPP⁺, the hydrogen bonding between MeOH and H₃DPP⁺ should be important for the stabilization of the monoprotonated porphyrin. Addition of other protic solvents (3%) in acetone, such as water and 2,2,2-trifluoroethanol, also allowed us to observe the H₃DPP⁺ formation with TFA; however, we just observed the formation of H₄DPP²⁺ in the presence of acetonitrile (5%) as a polar aprotic solvent in place of methanol with comparable permittivity. Thus, we conclude that the hydrogen bond formation of a protic solvent molecule with H₃DPP⁺ plays a crucial role to stabilize the monoacid.

   We also revealed that the acidity (pK_a) of an acid used for the protonation is an important factor for the selective formation of H₃DPP⁺: The smaller pK_a value of an acid, the higher formation yield of H₃DPP⁺. In the case of p-toluenesulfonic acid as a strong acid, the formation yield of the monoacid was 100%, indicating the complete selectivity in the monoacid formation. This result is consistent with the stepwise protonation of H₂DPP in benzonitrile even in the absence of methanol [1]. The higher selectivity for a strong acid should stem from weak hydrogen bonding of the corresponding conjugate base with protonated species of H₂DPP, allowing competitive interaction of the protic solvent molecule with H₃DPP⁺.

  We will also report the thermodynamics of the equilibrium of the protonation of H₂DPP in acetone-methanol mixed solvents.

Figure 1. A side view of the crystal structure of [H₃DPP](CF₃COO)(CH₃OH).

Reference

1. Honda, T.; Kojima, T.; Fukuzumi, S. Chem. Commun. 2009, 4994-4996.