A Tris-Aldehyde Porphyrin Synthon: Synthesis and Characterization of 5,10,15-tris-(4’-(4-Formylphenoxy) propoxyphenyl)-20-(4-nitrophenyl)-porphyrin

This article reports the synthesis and characterization of 5,10,15-tris-(4 ’ -(4-formylphe-noxy)propoxyphenyl)-20-(4-nitrophenyl)-porphyrin ( PN(OH) 3 A , Scheme 1) as an A 3 B type template for the development of porphyrin-based photosensitizers and photoactive reaction centers. The electron-withdrawing meso -4-nitrophenyl group attached to the porphyrin macrocycle is intended to influence the potential photochemical and photo-biological outcomes, and the three long-chain flexibly-linked free aldehyde groups offer a considerable range of synthetic scope.

In this paper, we report the synthesis (Scheme 1) of the porphyrin aldehyde PN(OH) 3 A of the type A 3 B bearing three-(4'-(4-formylphenoxy)propoxyphenyl) moieties (A) and one meso-nitrophenyl moiety (B).The compound is thus unique in having three formyl groups attached to the meso-positions through propoxyphenyl linkages.The compound PN(OH) 3 A has been characterized through 1 H NMR, UV-Vis, emission, and mass spectral techniques, as well as satisfactory elemental analysis.
Because the methods used to prepare the known precursor compounds are different from previously published reports, we have included their details here (see Experimental section).Some of the spectrometric details of the precursor compounds additionally provide an important basis of comparison for the new tris-aldehyde and are also included.In the initial step of the synthesis, a three-component one-pot reaction among 4-nitrobenzaldehyde, 4-formylphenyl propionate and pyrrole in refluxing propionic acid and nitrobenzene media led to the formation of a mixture of products.Extensive chromatographic separation run multiple times led to the successful isolation of 5,10,15-tri- in DMF at 50 C in the presence of K 2 CO 3 and a catalytic amount of KI.The tris porphyrin aldehyde PN(OH) 3 A was obtained in 59% yield.
The formation of the porphyrin macrocycles PN 3 and PN(OH) 3 was confirmed through the recorded 1 HNMR and mass spectra (Supplementary Materials).The compounds had been prepared by a different methodology earlier, 33 and our experiments confirm this previous work.The characterization details have been published elsewhere. 33onsistent with the data for its precursor compounds, the 1 H NMR spectra (Figure S3 and Table 1) of the porphyrin aldehyde PN(OH) 3 A conform to that of an A 3 B porphyrin with the b-pyrrole protons splitting as a doublet-singlet-doublet at 8.89 (d, 2H, J ¼ 4.7 Hz)-8.86 (s, 4H) -8.71 (d, 2H, J ¼ 4.7 Hz) ppm.The aromatic (4-nitrophenyl) protons, marked as H a and H b (Figure 1), resonated at 8.  S6) further affirmed the formation of PN(OH) 3 A.
The 1 H NMR spectral data of the 4-nitrophenyl-porphyrin derivative PN(OH) 3 A, with its three free aldehydes connected by flexible linkers through the meso-positions of the otherwise planar porphyrin macrocycle, suggested distortions of porphyrin planarity.The distortions in the molecular plane were evident in the aromatic signals at the mesogroups of the porphyrin ester and were even more evident upon functionalization with the long-chain aromatic aldehydes, as indicated by the 1 H NMR.
The comparative UV-Vis and emission spectral plots of the PN(OH) 3 A with precursors PN 3 and PN(OH) 3 are shown in Figure 2; the spectral data, along with the molar extinction coefficient and calculated Stokes shift have been presented in Table 2.5] The Soret band maxima of PN 3 , PN(OH) 3 and PN(OH) 3 A are observed at 422, 423 and 424 nm, respectively.The compounds also exhibit four Q-band absorptions centered at 518, 556, 596, and 651 nm for PN 3 ; 518, 557, 596 and 653 nm for PN(OH) 3 ; 518, 555, 593 and 650 nm for PN(OH) 3 A. Other than differences in the intensity of absorptions, no significant variations were observed.
The emission spectra of the compounds did exhibit effects of structural variations.The Q(0,0) emission band of the porphyrins PN 3 , PN(OH) 3 and PN(OH) 3 A were observed at 664, 670 and 659 nm, indicating a red shift of 6 nm of the emission maxima in going from the porphyrin ester PN 3 to the hydrolysis product PN(OH) 3 .The formation of the tris-aldehyde PN(OH) 3 A from PN(OH) 3 was accompanied by a blue shift of 11 nm in the Q(0,0) emission band.The Q(0,1) emission band of PN 3 , PN(OH) 3 and PN(OH) 3 A centered at 726, 728 and 723 nm, respectively, also indicates minor shifts along with a variation in emission intensity (Figure 2B).The calculated Stokes shifts of 242, 247, and 235 nm for PN 3 , PN(OH) 3 and PN(OH) 3 A, respectively, indicate structural reorganizations in the excited state.
In conclusion, we have successfully synthesized and characterized the tris-formyl porphyrin 5,10,15-tris-( 4 To the best of our knowledge, this is the first report of a porphyrin with a tris-aldehyde function of this type.The role of the meso-(4-nitrophenyl)porphyrin bearing three flexibly linked free aldehydes is potentially significant in the elaboration of photoactive porphyrin derivatives; [26][27][28][29]36 the title compound may thus serve as a synthon in the development of photobiologically important drugs and photosynthetic reaction centers.

Experimental section
4-Nitrobenzaldehyde, propionic acid and propionic anhydride (Sigma Aldrich) were used without further purification.Pyrrole (Sigma Aldrich) was freshly distilled before use.4-(3-Bromopropoxy)benzaldehyde was synthesized as previously reported. 374-Formylphenyl propionate, NaOH (SD Fine Chemicals), K 2 CO 3 , KI, nitrobenzene and NaHCO 3 were used as received from commercial sources.UV-visible absorption spectra were recorded using a PerkinElmer LAMBDA 750 UV/vis/NIR spectrophotometer, and emission spectra were recorded using a Fluoromax-4 spectrofluorometer (Horiba Scientific). 1 HNMR data were recorded with a Bruker Av III HD (DRX) 300 MHz  A modified version of the well-known Adler method 38 was employed to synthesize the porphyrin derivative PN 3 .Thus, propionic acid (170 mL) and nitrobenzene (10 mL) were added to an amber-colored 500 mL three-neck round bottom flask, equipped with a reflux condenser.The set-up was set to stir for 10 min at 110 C.After that, 4-nitrobenzaldehyde (2.18 g, 0.015 mol, 1 eq), 4-formylphenyl propionate (2.23 mL, 0.015, 1 eq)  and pyrrole (4 ml, 0.058 mol, 4 eq) were added to the flask and the stirring continued for 90 minutes at a temperature of 150 C.After that, the excess of propionic acid was removed by distillation.Neutralization of the crude residue to pH 7 was achieved by using 0.5 M ammonia.The residue was collected by filtration and thoroughly washed with deionized water followed by warm diethyl ether.The crude product was kept overnight before loading onto a silica column for separation.Silica gel 60-200 mesh was used as the stationary phase, while 7% MeOH in DCM was used as the eluent.The three-component reaction led to the formation of six compounds (of the type A 4 , A 3 B, c-A 2 B 2 , t-A 2 B 2 , AB 3 , B 4 , where A ¼ 4-propionyloxyphenyl and B ¼ 4-nitrophenyl), which were eluted out together to separate these from the tar like by-products.The fraction collected from the column was concentrated on a rotary evaporator and the concentrate was subjected to a second silica gel gravity percolation chromatography with silica gel 60-200 mesh as the stationary phase.A gradient (1-5%) of MeOH in DCM was used as the eluent.The target A 3 B porphyrin PN 3 eluted out with 2% MeOH in DCM.The fraction collected was concentrated on a rotary evaporator and the concentrate was dissolved in the minimum volume of DCM.After that, the pure compound was precipitated out by the careful addition of hexane, recovered by filtration and dried.Yield: 1.26 g, 10%, R f ¼ 0.45, DCM/MeOH, 98:2.UV-Vis (DMF, 10 lM Solution), k abs /nm (e/10 3 M À1 cm À1 ): 651 nm, (k max ; Q-band), 596 nm (k max ; Q-band), 556 nm (k max ; Q-band), 518 nm (k max ; Q-band), 422 nm (k max ; Soret band).Emission (DMF, 10 lM concentration), k ex ¼ 422 nm (S-band): 664 nm Q(0,0), 726 nm Q(0,1) with Stokes shift 242 nm Q(0,0)-B(0,0); 1 /z 876.3033, found 876.326.These data are consistent with those previously reported for this compound, prepared by a different route. 33

5,10,15-tris-(4-Hydroxyphenyl)-20-(4-nitrophenyl)porphyrin (PN(OH) 3 )
Compound PN 3 (0.125 g, 0.1766 mmol, 1 eq) was dissolved in DMF (35 mL) in a 500 mL round bottom flask.The flask was then charged with crushed NaOH (1.4 g) and the contents were subjected to stirring for 30 min.After that, 400 mL of deionized water was added and stirring continued for 30 more minutes.The reaction mixture was then neutralized to pH 7.0 by gradual addition of 6N HCl and the product finally recovered by solvent extraction with dichloromethane (DCM) (3 Â 80 mL) and water (3 Â 100 mL).The organic layer collected was additionally washed with water (3 Â 100 mL) before drying over anhydrous Na 2 SO 4 .The dried product-laden solvent was collected by filtration after 6 h, concentrated, and finally the compound was precipitated out by adding hexane gradually.The product was collected by filtration and dried.Yield: 0.85 g, 85%.R f ¼ 0.5, DCM/MeOH, 95:5.UV-Vis (DMF, 10 lM Solution), k abs /nm (e/10 3 M À1 cm À1 ): 653 nm, (k max ; Q-band), 596 nm (k max ; Q-band), 557 nm (k max ; Q-band), 518 nm (k max ; Q-band), 423 nm (k max ; Soret band).Emission (DMF, 10 lM concentration), k ex ¼ 423 nm (S-band): 670 nm Q(0,0), 728 nm Q(0,1) with Stokes shift 247 nm Q(0,0)-B(0,0); 1    A single-neck 25 mL amber-colored round bottom flask was charged with PN(OH) 3 (0.035 g, 0.0495 mmol, 1 eq) and DMF (9 mL).K 2 CO 3 (0.033 g, 0.246 mmol, 5 eq) was then added to the reaction vessel, the flask stoppered and the set-up was set to stir for 30 min at 50 C.This was followed by the addition of 4-(3-bromopropoxy)benzaldehyde (0.036 g, 0.148 mmol, 3 eq) and a catalytic amount of KI.The reaction system was set to stir at 50 C. TLC confirmed the completion of the reaction after 36 hours.The crude product was recovered through solvent extraction, by partitioning with dichloromethane (DCM) (3 Â 30 mL) and NaHCO 3 (3 Â 50 mL) solution.The organic layer was further washed with NaHCO 3 (2 Â 50 mL) solution and finally dried over anhydrous Na 2 SO 4 , filtered after 6 hours, and concentrated on a rotary evaporator.The crude concentrate obtained was loaded onto a silica gel column for further purification.The column was initially run with 50% DCM in hexane to remove any unreacted aldehyde.After that, the desired compound was eluted out with 3% MeOH in DCM.The collected fraction was concentrated in a rotary evaporator and resuspended in a minimum quantity of DCM.The compound was precipitated by gradual addition of hexane.The precipitate was recovered by filtration, dried, and kept under an atmosphere of nitrogen under refrigeration.Yield: 0.035 g, 59%.R f ¼ 0.5, DCM/MeOH, 97:3.

Table 1 .
1HNMR spectral data of PN 3 and PN(OH) 3 with calculated coupling constants and proton integration.