First synthesis of meso-substituted pyrrolo[1,2-a]quinoxalinoporphyrins

Summary A synthetic protocol for the construction of new meso-substituted pyrrolo[1,2-a]quinoxalinoporphyrins is described starting from 5-(4-amino-3-nitrophenyl)-10,15,20-triphenylporphyrin. The reaction of this porphyrin with 2,5-dimethoxytetrahydrofuran, followed by the reduction of the nitro group in the presence of NiCl2/NaBH4 afforded 5-(3-amino-4-(pyrrol-1-yl)phenyl)-10,15,20-triphenylporphyrin. This triphenylporphyrin underwent a Pictet–Spengler cyclization after the reaction with various aromatic aldehydes followed by in situ KMnO4 oxidation to form target porphyrin analogues in good yields. The structures of all synthesized products were established on the basis of spectral data and elemental analyses.

In recent years, numerous covalent or non-covalent supra-porphyrin arrays, based on donor-acceptor architectures have been constructed for mimicking the natural photosynthetic light harvesting systems [38][39][40]. Additionally, a variety of bio- logically important functional groups were also introduced on the periphery of meso-substituted porphyrins to develop efficient photosensitizers for photodynamic therapy applications [41][42][43]. However, the porphyrins with a pyrrolo[1,2-a]quinoxaline moiety at the meso-positions have not been synthesized and their photophysical properties have not been evaluated yet. By considering the biological and fluorescent properties of these two classes of heterocycles, we envisaged to combine both porphyrin and pyrrolo[1,2-a]quinoxaline units in a single molecular framework to generate novel meso-substituted pyrrolo[1,2a]quinoxalinoporphyrin analogues. Such hybrid molecules may prove useful for various biological studies and in the development of new photodynamic agents. Therefore, in continuation of our efforts to develop simple and efficient methods [44][45][46][47][48] for the synthesis of diverse porphyrin derivatives from mesotetraarylporphyrins, we wish to report herein the first synthesis and spectroscopic properties of a novel series of meso-substituted pyrrolo[1,2-a]quinoxalinoporphyrins.
The target products were purified by column chromatography over neutral alumina and obtained in 60-76% isolated yields. Furthermore, the π electron-rich free-base porphyrin dyads (4g and 4h) were converted to the corresponding zinc(II) porphyrins (5 and 6) in 84 and 87% yields, respectively, after the treatment with Zn(OAc) 2 ·2H 2 O in CHCl 3 /MeOH mixture for 30 minutes at room temperature (Scheme 2).
All synthesized porphyrins (2, 3, 4a-h, 5 and 6) were characterized on the basis of NMR, IR, UV-vis and mass spectral data in addition to elemental analysis. The proton NMR of newly prepared free-base meso-substituted pyrrolo[1,2-a]quinoxalinoporphyrins (4a-h) showed a characteristic singlet around δ −2.7 ppm for two NH protons of the porphyrin core. The β-pyrrolic protons of the porphyrin ring appeared in the downfield region between δ 8.85-9.01 ppm. A characteristic doublet at δ 8.9 and a double doublet at δ 8.3 ppm were assigned to the C-2 and C-6 protons of the meso-phenyl ring fused with the pyrroloquinoxaline moiety. The C-5 proton was found to be merged with nine other meso-phenyl protons and appeared as a multiplet between δ 7.75-7.77 ppm. The remaining six meso-phenyl protons appeared as a multiplet between δ 8.20-8.25 ppm along with a pyrrolic C-1′ proton. In the case of porphyrins (4a-f), the two pyrrolic C-2′ and C-3′ protons of the pyrroloquinoxaline ring appeared as a double doublet at around δ 7.06 ppm and a doublet at around δ 7.19 ppm, respectively. The 1 H NMR spectrum of porphyrin 4g displayed these pyrrolic C-2′ and C-3′ protons as a double doublet at δ 7.01 ppm and a doublet at around δ 6.74 ppm, whereas these pyrrolic protons appeared as multiplets between δ 7.09-7.24 ppm in the case of porphyrin 4h. In addition, porphyrin 4h and 6 showed a characteristic singlet for the CH 2 protons of the fluorenyl moiety at δ 4.0 and 3.9 ppm, respectively. The IR spectra of all the free-base pyrrolo[1,2-a]quinoxalinoporphyrins showed a peak between 3317-3318 cm −1 due to the NH bond stretching. The structures of porphyrins (2, 3, 4a-h, 5 and 6) were further supported by mass spectral analysis, which revealed the molecular ion peak to be [M + H] + . The electronic absorption and emission data of all the synthesized compounds are presented in Table 1.
The UV-vis spectra of newly prepared meso-substituted pyrrolo[1,2-a]quinoxalinoporphyrins (4a-h) in chloroform exhibited a typical intense Soret band at ~422 nm and four weaker Q bands at ~517, 552, 596 and 647 nm. In contrast, the zinc(II) pyrrolo[1,2-a]quinoxalinoporphyrin analogues 5 and 6 showed an intense Soret band at ~425 nm and two weaker Q bands at ~553 and 594 nm. In comparison to the TPP and Zn-TPP, the UV-vis spectra of free-base porphyrins 4a-h and zinc porphyrins (5 and 6) were found to be red-sifted by 3 to 4 nm. The electronic absorption spectra of selected free-base Table 1: Electronic absorption and emission data of porphyrins (2, 3, 4a-h, 5 and 6).

Compound
Absorption a λ max , nm (ε × 10 −4 , M −1 cm −1 ) Fluorescence a,b (λ em /nm) a Absorption and emission data were taken for CHCl 3 solutions of porphyrins at 298 K. b The excitation wavelength for emission data is 420 nm. porphyrins (4f, 4g, 4h and TPP) and zinc(II) porphyrins (5, 6 and Zn-TPP) are shown in Figure 1a,b. Besides the Soret and Q bands in porphyrins 4g, 4h, 5 and 6, an additional absorption peak originates at 280 and 320 nm due to the presence of pyrene and fluorene units, respectively. Thus, the electronic absorption spectra of these compounds demonstrated the features of both porphyrin and pyrene or fluorene subunits and suggest that there is no significant interaction between the attached chromophore and the porphyrin ring in the ground state.
The fluorescence spectra of porphyrins 4f, 4g, 4h, 5 and 6 were recorded in CHCl 3 at the excitation wavelength of 420 nm and are shown in Figure 1c,d. The free-base pyrrolo[1,2-a]quinoxalinoporphyrins 4f, 4g and 4h displayed an emission band and a weak shoulder at ~652 and ~717 nm. These emission bands are found to be slightly intense in comparison to the TPP (Figure 1c). Similarly, the zinc(II) pyrrolo[1,2-a]quinoxalinoporphyrins 5 and 6 showed two fluorescence bands at ~605 and 652 nm, which are also found to be slightly intense when compared to the emission bands of Zn-TPP (Figure 1d).

Supporting Information
Supporting Information File 1 Experimental details and characterization data.