Regioselective reduction of 5-aryl-10,15,20-tris(pyridyl) porphyrin to 5-aryl-10,15,20-tris(pyridyl)dihydroporphyrin (chlorin)

Article abstract of DOI:10.1142/S1088424619501438

Dihydroporphyrins or chlorins differ from porphyrins only by saturation of a peripheral double bond of the macrocycle. However, this small structural difference leads to a significant increase of the absorption band at approximately 650 nm, which makes them very interesting candidates for photodynamic therapy applications. The reduction of porphyrins bearing two, three or four pyridyl substituents with tin(II) chloride has been developed for the synthesis of dihydroporphyrins in yields of 15-73%. The reduction of 5-(aryl)-10,15,20-tris(2 or 4-pyridyl)porphyrin with tin(II) chloride dihydrate demonstrated good regioselectivity. Porphyrins with one meso-aryl bearing one electron-donating group (EDG) gave 5-aryl-10,15,20-tris(2-or 4-pyridyl)-17,18-dihydroporphyrins in 17-72% yield. Porphyrins with one meso-aryl bearing one or more electron-withdrawing groups (EWG) gave 5-aryl-10,15,20-tris(4-pyridyl)-17,18-dihydroporphyrins or 5-aryl-10,15,20-tris(4-pyridyl)-7,8-dihydroporphyrins in 15-21% yield and isobacteriochlorin. We have also proven the possibility of functionalizing these compounds to design new regioisomerically pure photosensitizers.

Full text of DOI:10.1142/S1088424619501438

This is a JAM - Just Accepted Manuscript
Journal of Porphyrins and Phthalocyanines
Article Title:
Author(s):
Regioselective reduction of 5-aryl-10,15,20-tris(pyridyl) porphyrin to 5-aryl-
10,15,20-tris(pyridyl)dihydroporphyrin (chlorin)
Frederique Bregier, Jeremy Godard, Jordan Thiais, Soukaina Bouramtane,
Alexia Moulin, Yves Champavier, Alexis Mailleau, Vincent Chaleix and
Vincent Sol
DOI:
10.1142/S1088424619501438
To be cited as:
Ewen Bodio, Franck Denat, Christine Goze, BODIPYS and aza-BODIPYS derivatives as
promising fluorophores for in vivo molecular imaging and theranostic applications, Journal of
Porphyrins and Phthalocyanines, doi: 10.1142/S1088424619501438
Received: 27 August, 2019
Accepted: 27 September, 2019
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Regioselective reduction of 5-aryl-10,15,20-tris(pyridyl)
porphyrin to 5-aryl-10,15,20-tris(pyridyl)dihydroporphyrin
(chlorin)
Frédérique Brégier*a, Jérémy Godarda, Jordan Thiaisa, Soukaina Bouramtanea,
Alexia Moulina, Yves Champavierb, Alexis Mailleaub, Vincent Chaleixa and Vincent
Sola
a
Université de Limoges, PEIRENE, EA 7500, 123 Avenue Albert Thomas, 87060 Limoges Cedex, France.
b
BISCEm, FR3503 GEIST, Centre de Biologie et de Recherche en Santé (CBRS), 2 rue du Dr Marcland, 87025
Limoges Cedex, France.
Received date
Accepted date
ABSTRACT:
Dihydroporphyrins or chlorins differ from porphyrins only by saturation of a peripheral double bond
of the macrocycle. However, this small structural difference lead to significant increase of the
absorption band at approximately 650 nm, which make them very interesting candidates for
photodynamic therapy applications. The reduction of porphyrin bearing two, three or four pyridyl
substituents with tin(II) chloride has been developed for the synthesis of dihydroporphyrins in yields
of 15–73%. The reduction of 5-(aryl)-10,15,20-tris(2 or 4-pyridyl)porphyrin with tin(II) chloride
dihydrate demonstrated good regioselectivity. Porphyrin with one meso-aryl substituted with one
electron-donating groups (EDG) gave 5-aryl-10,15,20-tris(2- or 4-pyridyl)-17,18-dihydroporphyrins
in 17-72% yield. Porphyrin with one meso-aryl substituted with one electron-withdrawing groups
(EWG) gave 5-aryl-10,15,20-tris(4-pyridyl)-17,18-dihydroporphyrins or 5-aryl-10,15,20-tris(4-
pyridyl)-7,8-dihydroporphyrins in 15-21% yield and isobacteriochlorin. We have also proved the
possibility to functionalize these compounds to design new regioisomerically pure photosensitizers.
KEYWORDS: Chlorins, Porphyrins, Reduction, Synthesis
*Correspondence to: Dr. Frédérique Brégier, PEIRENE, EA7500, Université de Limoges, Faculté des Sciences et Techniques,
Campus La Borie, 123 avenue Albert Thomas, 87060 LIMOGES Cedex, France. Telephone: (+33) 5.55.45.72.19. Email:
frederique.bregier@unilim.fr
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INTRODUCTION
Photodynamic therapy (PDT) is an alternative and a non-invasive cancer treatment requiring the simultaneous
presence of three elements: photosensitive molecule, light source and molecular oxygen. The most used
photosensitizers in PDT are porphyrins and their derivatives such as chlorins. Chlorins (dihydroporphyrins) differ
from porphyrins only by saturation of a peripheral β,β’-pyrrolic double bond of the macrocycle. However, this small
structural difference leads to significant changes in the absorption spectrum. Chlorins exhibit a strong absorption
band in the violet-blue region (∼380−450 nm), the B band whose molar extinction coefficient (ε) varies between
50000-400000 M-1.cm-1 and a moderately strong band in the red region (∼600−700 nm), the Qy band, whose molar
extinction coefficient (ε) varies between 30000-100000 M-1.cm-1[1]. The enhancement of the absorption intensity in
the red region (in optical transparency window of biological tissues) makes them better candidates for photodynamic
therapy than their porphyrin analogues. Among different PDT photosensitizers, several chlorins were clinically
approved as cancer treatments. These include, Foscan® (meso-tetra-(m-hydroxyphenyl)chlorin, temoporfin,
mTHPC; Biolitec AG)[2], Visudyne® (verteporfin, benzoporphyrin derivative monoacid ring A, BPD-MA;
Novartis Pharmaceuticals)[3], Laserphyrin® (talaporfin sodium monoaspartyl chlorin(e6); Meiji Seika Pharma Co.,
Ltd.)[4]... In addition, great efforts of chlorins functionalization were made to improve PDT efficiency [5, 6].
5,10,15,20-Tetrakis(1-methylpyridinium-4-yl) porphyrin tosylate is also of great interest and have been reported
to inhibit cervical cancer growth significantly with no apparent side effect [7]. In order to increase the absorption in
the red and to graft latter by covalent bond a group inducing selectivity toward tumor cells, we are interested by the
synthesis of non-symmetric 5-aryl-10,15,20-trispyridylchlorin. These chlorins could be classically prepared by
reduction of the corresponding unsymmetrical porphyrin using diimide generated in situ from p-
toluenesulfonhydrazide[8]. This method leads, in a first-step, to the formation of bacteriochlorins, which can be
oxidized subsequently with o-chloranil to chlorins. This two-step process affords regioisomeric non-separable
chlorins mixtures. This method is however the most used to date [9-11]. Some examples of regioselective synthesis
have been proposed in recent years[12] but there is to our knowledge not direct dihydrogenation of porphyrins in
one regioselective step.
Stannous chloride in an acidic medium is known since longtime to reduce aryl nitro compounds in aryl
amine[13,14] It has been used for decades to prepare meso-tetraarylporphyrins bearing aminophenyl groups starting
from corresponding nitroarylporphyrins[15]. In 1981, Zimmer et al. have developed a simple and rapid detection
test of tin(II) using 5,10,15,20-Tetrakis(1-methylpyridinium-4-yl) porphyrin tosylate. This protocol involved the
reduction of the porphyrin in the presence of acidic Sn(II) solutions to dihydroporphyrin, producing a red color
change[16]. Moreover meso substitution with pyridyl groups has long been known to affect the porphyrin reduction
potential[17]. In 2013, Kumar et al. reported the obtention of the 5-(4-aminophenyl)–10,15,20–tris(4-
pyridyl)porphyrin from 5-(4-nitrophenyl)–10,15,20–tripyridylporphyrin in 70% yield [18]. However, by reproducing
the experiment, the major product was not the expected porphyrin, but the corresponding 5-(4-aminophenyl)–
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10,15,20–tripyridylchlorin. In connection with our research program on the synthesis of new photosensitizers for
photodynamic therapy application[19-24], and very interested by these unexpected results, we decide to explore this
reaction and these limits. So, we report, in the present paper full experimental data concerning the synthesis and
characterization (1H, 13C NMR, MS spectrometry, and absorption spectroscopy) of some aminophenyl
trispyridylchlorin derivatives.
RESULTS AND DISCUSSION
Synthesis of porphyrins with pyridyls meso-substituents
Different porphyrins bearing pyridyls and aryls substituents were prepared by a propionic acid-mediated
condensation developed by Adler-Longo et al. and adapted by Little et al.[25, 26]. This statistical approach leads to
four different porphyrins in a non-negligible amount (Scheme 1). After chromatographic separations, the
asymmetric A3B porphyrins 2–10 and cis-A2B2 porphyrins 11-15 were isolated in yields of 3%-6% and 2%-6%,
1
respectively. Porphyrins 3-16 were characterized by H and 13C NMR spectroscopy, and ESI-HRMS spectrometry
(see Experimental Section and Supporting Information). <Scheme 1>
Reaction of 5-(4-nitrophenyl)-10,15,20-tris(4-pyridyl)porphyrin (2) with Tin(II) chloride
Synthesis of 5-(4-aminophenyl)-10,15,20-tris(4-pyridyl)-17,18-dihydroporphyrin (17)
Firstly, the reduction of 5-(4-nitrophenyl)-10,15,20-tris(4-pyridyl)porphyrin (2) was investigated. The porphyrin
2 in 6N HCl solution was treated with tin(II) chloride dihydrate and the resulting solution was stirred for two hours
at 65 °C. After neutralization by addition of sodium bicarbonate, the mixture was extracted with dichloromethane.
Porphyrin and chlorin are then separated by repeating preparative thin-layer chromatography. The chlorin 17 has
been isolated with 73% yield. The mass spectrum showed the appropriate parent ion peak at 635.27 (M+H+). The
1
UV-vis spectrum of 17 is characteristic of metal-free chlorins. Interestingly, the H NMR spectrum showed the
presence of a single regioisomer. This result suggested that in these reaction conditions the reduction of porphyrin
17 is regioselective. The product displayed only one singlet at 4.12 ppm characteristic of the reduced β-pyrrolic
protons, six doublets (δ 8.12, 8.15, 8.32, 8.52, 8.55 and 8.72) in the β-proton region and one singlet at -1.35 ppm
corresponding to the internal pyrrolic NH protons. The structural elucidation of obtained regioisomer was achieved
by means of 2D-NOESY NMR experiments (Figure 1). NOESY cross peaks indicated through-space interactions
between the reduced β-pyrrolic protons (H17/H18 4.12 ppm) and the four ortho pyridyl protons in meso position 15
and 20 (Hf 7.83 ppm). Additional cross peaks, between H3 (8.72 ppm) and the two ortho aryl protons (Hb 7.84) and
H7 (8.55 ppm) and the same two ortho aryl protons (Hb 7.84) can be observed. On the basis of these analyzes, we
assumed that the reduction takes place preferentially on a pyrrole located between two pyridyl groups (Scheme 2).
Further interpretation of the 2D spectra allowed assignment of each proton. The 13C NMR spectrum (Figure 2) was
also fully assigned with the help of two-dimensional NMR experiments (HSQC and HMBC). The 13C NMR
spectrum of chlorin 17 showed well defined signals for α and β carbons in comparison with porphyrin 2. In the
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reduced macrocycle of the chlorin, the effect of NH tautomerism seemed smaller. We supposed that the activation
barrier for the NH tautomerism is larger than that of porphyrin. <Scheme 2> <Figure 1> <Figure 2>
Examination of the influence of the reactions parameters
In order to rapidly evaluate the influence of experimental condition parameters, we investigated a design of
experiment according to L9 orthogonal array of the Taguchi method. This approach allowed us to conduct only nine
experiments instead of 34 (81) using the simple factorial design[27]. The selected factors and their levels were listed
in SI Table1. Yields of the chlorin 17 and 5-(4-aminophenyl)-10,15,20-tris(4-pyridyl)porphyrin (2NH2) were studied
as a function of four factors, temperature (35-100 °C), reaction time (2-18h), HCl concentration (4-8 M) and
1
equivalent number of tin(II) chloride (0.5-3) at three levels each. Yields were determined by H NMR analysis of
crude using 3-methoxybenzaldehyde as an internal standard. Structure of Taguchi’s orthogonal array design and
yields of the chlorin 17 and porphyrin 2NH2 were listed in SI Table2 and graphically represented in the Figure 3.
These results show a clear influence of the different parameters in the reduction reaction of porphyrin to chlorin. A
lower temperature than 35° C does not seem sufficient while a higher temperature than 100 ° C affects the yield of
chlorin as well as porphyrin. A long reaction time leads to an increase in the amount of porphyrin 2NH2, which can
be explained by a reoxidation of chlorin to the original porphyrin over time. A hydrochloric acid concentration of
6N promotes the reduction of porphyrin to chlorin. Finally, an increase in the amount of tin(II) chloride makes it
possible to increase the yield of chlorin. However, the usable quantity of the latter is limited by complication of the
extraction step. <Figure 3>
Influence of the number of pyridyls groups and electron-donating or -withdrawing nature of the others
substituents
Secondly, we sought to determine whether the presence of one or more electron-donating or electron-
withdrawing groups on meso-aryl position, the number of pyridyls groups and their relative position influenced the
yields and the regioselectivity of the reduction. The results were presented in the Table 1. The low yields of 20 could
be explained by difficult chromatographic separation between porphyrin 5 and chlorin. The presence of electron-
withdrawing meso-substituents led to a decrease in the synthesis of chlorin yield. Chlorins 22 and 23 were obtained
in 21% and 16% yield respectively. This decrease in chlorin amount was accompanied by the appearance of another
compound in a significant amount. The UV-visible absorption spectrum allowed to identify these compounds as
isobacteriochlorins (Figure 4)[28]. <Figure 4>
For all chlorins 18-23 the parent ions [M+H]+ can be seen in ESI–MS spectra. The NMR spectra confirm the
1
obtention of one single chlorin. Examination of the 2D H-13C- HMBC spectrum of compounds 18-22 showed
correlation between the singlet of the four β-pyrrolic protons of the hydrogenated pyrrole unit at 4.1-4.2 ppm and the
two signal for the meso-carbon C15 and C20 atoms. These results allowed us to conclude on the formation of the 5-
1
aryl-10,15,20-tris(4-pyridyl)-17,18-dihydroporphyrin. In the case of the compound 23, the 2D H-13C HMBC
spectrum showed correlation between the apparent singlet of the four β-pyrrolic protons of the hydrogenated pyrrole
unit at 4.23 ppm and the two signals for the meso-carbon C5 and C10 atoms. In addition, β-pyrrolic protons H17 and
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H18 appeared as a singlet whereas the inner NH protons were split into two broad singlets. These data suggested that
the reduction taked place preferentially on a pyrrole located between a pyridyl group and the pentafluorophenyl
group to give 5-pentafluorophenyl-10,15,20-tris(4-pyridyl)-7,8-dihydroporphyrin 23.
The assay reduction of AB3 porphyrin carrying only one pyridyl group and trans-A2B2-porphyrin 16 did not
work. By contrast, under the conditions used, the porphyrins cis-A2B2 11-15 could be reduced to corresponding
chlorin. However, the analysis of the proton NMR spectrum revealed the presence of a regioisomeric mixture for the
chlorins 24, 25 and 27 in a ratio of 7:3, 6:5, 5.5:4.5 respectively. The structural elucidation of the two obtained
regioisomers in the reaction of porphyrin 11 with tin(II) chloride dihydrate was achieved by means of 2D-NOESY
NMR experiments. NOESY cross peaks indicated through-space interactions between the four reduced β-pyrrolic
protons (H17/H18 4.12 ppm) and the four ortho pyridyl protons in meso position 15 and 20 (Hf 7.81 ppm). Additional
cross peaks, between the two β-protons singlet at 8.43 ppm and the two ortho aryl protons (Hb 7.81) can be
observed. On the basis of these analysis, we assumed that the main regioisomer is the 5,10-(4-methoxyphenyl)-
1
15,20-tris(4-pyridyl)-17,18-dihydroporphyrin. The multiplication of the signals in the H NMR spectrum for the
second regioisomers suggested a weaker symmetry compound: 5,10-(4-methoxyphenyl)-15,20-tris(4-pyridyl)-2,3-
dihydroporphyrin. The chlorins 26 and 28 were isolated as a single regioisomer. In the case of 26, regioisomerism
could be explained by a steric hindrance of the methoxy group present at the ortho-position of aryl substituents
1
which could prevent the approach of tin(II) chloride. The 2D H-13C HMBC spectrum of 28 showed correlation
between the singlet of the four β-pyrrolic protons of the hydrogenated pyrrole unit at 4.26 ppm and the two signals
for the meso-carbon C5 and C10 atoms. These data suggested that the reduction taked place preferentially on a
pyrrole located between the pentafluorophenyl substituents to give 5,10-bis(pentafluorophenyl)-15,20-bis(4-
pyridyl)-7,8-dihydroporphyrin 28. Moreover, in the 1H NMR spectrum of 28, the presence of the isobacteriochlorin
29 can be observed (Figure S67). <Table 1>
A4-type porphyrins have also been tested. The A4 porphyrin 1 have shown interesting results. The UV-Visible
spectrum of crude product showed an absorption band at 745 nm which is characteristic of bacteriochlorin. 1H NMR
spectrum (Figure 5) revealed the presence of four different compounds. The starting porphyrin 1, the chlorin 30, the
bacteriochlorin 31 and the iso-bacteriochlorin 32 were estimated to constitute 29%, 18%, 6% and 47% respectively
of the mixture. Chlorin 30 was isolated in 15% and characterized by NMR, HRMS and UV/Vis spectroscopy.
<Figure 5>
These results clearly highlight the importance of electron-withdrawing groups on porphyrin to allow reduction of
macrocycle to dihydroporphyrin in the presence of tin(II) chloride. Electron-withdrawing meso-substituents on
porphyrin are known to decrease the potential needed to reduce porphyrin[17]. It would appear that reduction was
achieved at the pyrrole unit which is presumably more electron-deficient than the others. The presence of more than
three electron-withdrawing meso-substituents led to the formation of isobacteriochlorins. Electronic influences on
the reactivity of porphyrin β-pyrrolic positions have already been put forward[29-31]. Cavaleiro et al. have obtained
by catalytic hydrogenation of 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin with H2/10% Pd/C corresponding
isobacteriochlorin[32].
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Examination of the influence of the position of the nitrogen atom in pyridyls substituents
Pyridyl substituents play also a crucial role in this reduction reaction. To further understand the mechanism of
this reaction, the reactions with porphyrins 9 and 10 were investigated. The reaction with the porphyrin 9 led to 5-(4-
aminophenyl)-10,15,20-tris(3-pyridyl)porphyrin (9NH2) in nearly quantitative yield, whereas with the porphyrin 10,
5-(4-aminophenyl)-10,15,20-tris(2-pyridyl)chlorin (33) was obtained in 54% yield. Reduction potentials of meso-
pyridyl substituted porphyrins are similar whatever the relative position of the nitrogen atom in the pyridyl ring[17].
Therefore, the low reduction potential alone of these porphyrins cannot suffice to explain these results and the
mechanism shown in Scheme 3 was proposed. By addition of hydrogen chloride pyridyl substituents and the core of
the porphyrins are protonated. In the first step of the reaction, tin(II) chloride provided one electron which was taken
up by the porphyrin to form the corresponding radical anion. This intermediate state could be stabilized by
delocalization of the negative charge to the pyridinium nitrogen atom. The following possible steps were a second
electron transfer and two additional protonations by the hydrochloric acid to form the chlorin. <Scheme 3>
Functionalization of 5-(4-aminophenyl)-10,15,20-tris(4-pyridyl)-17,18-dihydroporphyrin (17)
These chlorins could be used as precursors for the design of new photosensitizers for anticancer and antimicrobial
photodynamic therapy. The amino group of the chlorin 17 could be easily functionalized (Scheme 4). It was
converted into azide using the Sandmeyer reaction by treatment with sodium nitrite and sodium azide in water to
give chlorin 34 in 26% yield. Chlorin 17 was also acylated with glutaric anhydride to give chlorin 35 in 77% yield.
Chlorins 34 and 35 may be later covalently bound to tumor-targeting agents by copper-catalyzed azide-alkyne
cycloaddition[33] and esterification[34], respectively. <Scheme 4>
From chlorin 17, we have designed and prepared a water soluble chlorin with a triphenylphosphonium group with
the aim to obtain
a new mitochondria-targeted photosensitizer (Scheme 5). In a first step, (3-
carboxypropyl)triphenylphosphonium bromide was activated with ethylchloroformate in presence of trimethylamine
followed by the addition of chlorin 17. The compound 36 was obtained in 48% yield. The N-methylation of 36 with
an excess of methyl iodide in DMF gave the cationic desired compound in 60% yield. The structure of 37 was
confirmed by NMR spectroscopy (Figure S86 and S87). <Scheme 5> In order to evaluate the oxidative stability of
the chlorin 37, an aqueous solution was analysed by UV-Vis at different time intervals over a 72h period (Figure
S88). Very little changes were observed, only a slight decrease in the overall absorption spectrum which could be
attributed to a little aggregation in water.
EXPERIMENTAL
Materials
All reagents, solvents and chemicals were purchased from Sigma-Aldrich, VWR, Acros, Fisher chemical, Carlo
Erba and Alfa Aesar. Triethoxysilane (TEOS) and pyrrole were distilled under reduced pressure before use.
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Analytical thin layer chromatography (TLC) were performed on Silica plates (Kieselgel 60 F254, thickness 0.2 mm,
Merck) and revealed by direct observation. Purifications by column chromatography were carried out using silica
gel 60 (Merck, 0.015-0.040 mm). The porphyrins to be purified are solubilized in a minimum of solvent and fixed
on Florisil® (VWR, 60-100 mesh). Purifications by thin-layer chromatography were carried out on 2 mm silica gel
plates (Merck, 60 P F254).
5,10,15,20-tetrakis(4-pyridyl)porphyrin
prepared according to the literature[18].
1 and 5-(4-nitrophenyl)–10,15,20–tris(4-pyridyl)porphyrin 2 were
Analytical methods
NMR spectra were recorded on a AscendTM500 Bruker NMR spectrometer. All compounds are calibrated to
tetramethylsilane. Quaternary carbons at the α-position of the N atoms of the free base porphyrin have long
relaxation time, which result in very broad signals that could not be detected. UV–vis spectra were recorded on a
double beam spectrophotometer AnalytikaJena SPECORD 210, using 10 mm quartz cells. High resolution
electrospray ionization mass spectra (HR ESI-MS) were performed on a Bruker Q-TOF maXis mass spectrometer,
coupled to an Ultimate 3000 RSLC chain (Dionex); by the ICOA/CBM (FR2708) platform (Orleans University).
General procedure for the preparation of porphyrins
Arylaldehyde (1 equiv.) and pyridinecarboxaldehyde (3 equiv.) were added to a round bottom flask containing
propionic acid at 110 °C. Pyrrole (4 equiv.) was then added dropwise and the reaction mixture refluxed for 4 h.
After cooling down to room temperature, propionic acid was removed by distillation under reduced pressure. The
crude brown solid was adsorbed over Florisil® and purified by repeated column chromatography with
chloroform/methanol, where it was possible to isolate the two porphyrins A3B and Cis-A2B2.
A3B porphyrins
1
5-(4-methoxyphenyl)-10,15,20-tris(4-pyridyl)porphyrin (3). Purple solid (140 mg, 3% yield). H NMR (500
MHz, CDCl3): δH, ppm -2.85 (s, 2H, NH), 4.10 (s, 3H, OCH3), 7.30 (d, J=8.5 Hz, 2H, Hc), 8.11 (d, J=8.5 Hz, 2H,
Hb), 8.15 (d, J=5.6 Hz, 6H, Hf), 8.81 (d, J=4.6 Hz, 2H, Hβ-pyrrolic), 8.84 (s, 4H, Hβ-pyrrolic), 8.96 (d, J=4.6 Hz, 2H, Hβ-
pyrrolic), 9.04 (m, 6H, Hg). 13C NMR (125 MHz, CDCl3): δC, ppm 55.6 (1C, OCH3), 112.5 (2C, Cb), 116.9 (1C, C15),
117.4 (2C, C10 C20), 121.7 (1C, C5), 129.3 (6C, Cf), 131.0 (6C, Cβ-pyrrolic), 132.4 (2C, Cβ-pyrrolic), 133.8 (1C, Ca), 135.6
(2C, Cc), 148.38 (4C, Cg), 148.42 (2C, Cg), 149.97 (1C, Ce’), 150.04 (2C, Ce), 159.7 (1C, Cd) Quaternary carbons at
the α-position are missing. ESI-HR m/z: calcd.exact mass for C42H30N7O: 648.2506 [M+H]+, found: 648.2501
[M+H]+. UV-vis (CH2Cl2): λmax, nm (log ε) 418 (5.60), 515 (4.29), 550 (3.86), 591 (3.79), 646 (3.54).
1
5-(3-methoxyphenyl)-10,15,20-tris(4-pyridyl)porphyrin (4). Purple solid (264.3 mg, 5.6% yield). H NMR
(500 MHz, CDCl3): δH, ppm -2.89 (s, 2H, NH), 3.99 (s, 3H, OCH3), 7.36 (ddd, J3=8.4 Hz, J5=0.8 Hz, 1H, Hd), 7.66
(t, J3=7.9 Hz, 1H, Hc), 7.76 (dd, J4=1.6 Hz, J5=0.8 Hz, 1H, Hb’), 7.80 (d, J=7.4 Hz, 1H, Hb), 8.13 (m, 6H, Hf), 8.79
(d, J=4.6 Hz, 2H, Hβ-pyrrolic), 8.83 (s, 4H, Hβ-pyrrolic), 8.96 (m, 8H, Hβ-pyrrolic / Hg). 13C NMR (125 MHz, CDCl3): δC,
ppm 55.5 (1C, OCH3), 113.7 (1C, Cd), 117.1 (1C, C15), 117.4 (2C, C10 C20), 120.7 (1C, Cb’), 121.4 (1C, C5), 127.65
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(1C, Cb), 127.70 (1C, Cc), 129.3 (6C, Cf), 131.1 (8C, Cβ-pyrrolic), 142.8 (1C, Ca), 148.28 (4C, Cg), 148.31 (2C, Cg’),
149.99 (1C, Ce’), 150.02 (2C, Ce), 158.1 (1C, Cc’) Quaternary carbons at the α-position are missing. ESI-HR m/z:
calcd.exact mass for C42H30N7O: 648.2506 [M+H]+, found: 648.2499 [M+H]+. UV-vis (CH2Cl2): λmax, nm (log ε)
417 (5.63), 513 (4.26), 548 (3.76), 589 (3.75), 644 (3.41).
1
5-(2-methoxyphenyl)-10,15,20-tris(4-pyridyl)porphyrin (5). Purple solid (149.2 mg, 4.6% yield). H NMR
(500 MHz, CDCl3): δH,ppm -2.83 (s, 2H, NH), 3.61 (s, 3H, OCH3), 7.36 (m, 2H, Hc Hc’), 7.80 (dt, J3=8.0 Hz, J4=1.6
Hz, 1H, Hd), 7.99 (dd, J3=7.3 Hz, J4=1.5 Hz, 1H, Hb), 8.14 (m, 6H, Hf), 8.78 (d, J=4.7 Hz, 2H, Hβ-pyrrolic), 8.83 (s,
4H, Hβ-pyrrolic), 8.87 (d, J=4.7 Hz, 2H, Hβ-pyrrolic), 9.03 (m, 6H, Hg). 13C NMR (125 MHz, CDCl3): δC, ppm 55.8 (1C,
OCH3), 111.0 (1C, Cc), 117.1 (1C, C15), 117.2 (2C, C10 C20), 117.7 (1C, C5), 119.6 (1C, Cc’), 129.3 (6C, Cf), 130.2
(1C, Cd), 130.3 (1C, Ca), 131.0 (6C, Cβ-pyrrolic), 132.0 (2C, Cβ-pyrrolic), 135.5 (1C, Cb), 148.34 (4C, Cg), 148.37 (2C,
Cg’), 150.1 (3C, Ce), 159.3 (1C, Cb’) Quaternary carbons at the α-position are missing. ESI-HR m/z: calcd.exact mass
for C42H30N7O: 648.2506 [M+H]+, found: 648.2508 [M+H]+. UV-vis (CH2Cl2): λmax, nm (log ε) 417 (5.63), 513
(4.28), 547 (3.73), 589 (3.75), 644 (3.37).
1
5-(phenyl)-10,15,20-tris(4-pyridyl)porphyrin (6). Purple solid (502 mg, 5.6% yield). H NMR (500 MHz,
CDCl3): δH,ppm -2.87 (s, 2H, NH), 7.79 (m, 3H, Hc Hc’ Hd), 8.16 (d, J3=5.8 Hz, 6H, Hf), 8.20 (m, 2H, Hb Hb’), 8.82
(d, J3=4.7 Hz, 2H, Hβ-pyrrolic), 8.85 (s, 4H, Hβ-pyrrolic), 8.92 (d, J=4.7 Hz, 2H, Hβ-pyrrolic), 9.05 (m, 6H, Hg). 13C NMR
(125 MHz, CDCl3): δC, ppm 117.1 (1C, C15), 117.4 (2C, C10 C20), 121.7 (1C, C5), 126.9 (2C, Cc), 128.1 (1C, Cd),
129.4 (6C, Cf), 131.2 (8C, Cβ-pyrrolic), 134.5 (2C, Cb), 141.5 (1C, Ca), 148.40 (4C, Cg), 148.43 (2C, Cg’), 149.97 (1C,
Ce’), 150.01 (2C, Ce) Quaternary carbons at the β and α-position are missing. ESI-HR m/z: calcd.exact mass for
C41H27N7: 618.2406 [M+H]+, found: 618.2400 [M+H]+. UV-vis (CH2Cl2): λmax, nm (log ε) 417 (5.59), 514 (4.22),
548 (3.72), 589 (3.69), 649 (3.60).
1
5-(4-Iodophenyl)-10,15,20-tris(4-pyridyl)porphyrin (7). Purple solid (207 mg, 5.3% yield). H NMR (500
MHz, CDCl3): δH,ppm -2.90 (s, 2H, NH), 7.92 (d, J3=8.1 Hz, 2H, Hc), 8.10 (d, J3=8.1 Hz, 2H, Hb), 8.15 (d, J3=5.3
Hz, 6H, Hf), 8.83 (d, J3=4.7 Hz, 2H, Hβ-pyrrolic), 8.85 (s, 4H, Hβ-pyrrolic), 8.90 (d, J=4.6 Hz, 2H, Hβ-pyrrolic), 8.15 (d,
J3=5.3 Hz, 6H, Hg). 13C NMR (125 MHz, CDCl3): δC, ppm 94.6 (1C, Cd), 117.3 (1C, C15), 117.6 (2C, C10 C20), 120.0
(1C, C5), 129.3 (6C, Cf), 131.2 (8C, Cβ-pyrrolic), 136.1 (4C, Cb Cc), 141.1 (1C, Ca), 148.4 (6C, Cg), 149.88 (1C, Ce’),
149.90 (2C, Ce) Quaternary carbons at the α-position are missing. ESI-HR m/z: calcd.exact mass for C41H27IN7:
744.1367 [M+H]+, found: 744.1359 [M+H]+. UV-vis (CH2Cl2): λmax, nm (log ε) 417 (5.58), 513 (4.25), 548 (3.79),
589 (3.76), 644 (3.44).
1
5-(pentafluorophenyl)-10,15,20-tris(4-pyridyl)porphyrin (8). Purple solid (426.1 mg, 6.0% yield). H NMR
(500 MHz, CDCl3): δH,ppm -2.88 (s, 2H, NH), 8.16 (m, 6H, Hf), 8.86 (m, 6H, Hβ-pyrrolic), 8.92 (d, J=4.6 Hz, 2H, Hβ-
pyrrolic), 9.06 (d, J3=5.7 Hz, 6H, Hg). 13C NMR (125 MHz, CDCl3): δC, ppm 101.8 (1C, C5), 118.1 (2C, C10 C20),
118.9 (1C, C15), 129.24 (2C, Cf), 129.29 (4C, Cf), 131.3 (8C, Cβ-pyrrolic), 148.47 (2C, Cg), 148.51 (4C, Cg), 149.51
(2C, Ce), 149.63 (1C, Ce’) In 13C NMR Quaternary carbons at the α-position and pentafluorophenyl signals were not
observed due to C-F coupling. ESI-HR m/z: calcd.exact mass for C41H23F5N7: 708.1930 [M+H]+, found: 708.1923
[M+H]+. UV-vis (CH2Cl2): λmax, nm (log ε) 415 (5.59), 511 (4.30), 544 (3.63), 586 (3.79), 642 (3.20).
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Accepted manuscript to appear in JPP
1
10-(4-nitrophenyl)-5,15,20-tris(3-pyridyl)porphyrin (9). Purple solid (175 mg, 2.8% yield). H NMR (500
MHz, CDCl3): δH,ppm -2.81 (s, 2H, NH), 7.77 (dd, J=5.7 Hz, J=6.0 Hz, 3H, Hg), 8.39 (d, J=7.2 Hz, 2H, Hc), 8.53 (d,
J=6.2 Hz, 3H, Hh), 8.64 (d, J=8.1 Hz, 2H, Hb), 8.81 (d, J=4.1 Hz, 2H, Hβ-pyrrolic), 8.87 (m, 6H, Hβ-pyrrolic), 9.07 (d,
J=4.3 Hz, 3H, Hf), 9.45 (m, 3H, Hf’). 13C NMR (125 MHz, CDCl3): δC, ppm 116.9 (2C, C10 C20), 117.0 (1C, C15),
117.9 (1C, C5), 122.0 (2C, Cb), 122.1 (3C, Cg), 131.6 (8C, Cβ-pyrrolic), 135.1 (2C, Cc), 137.6 (1C, Ca), 140.9 (3C, Ch),
147.9 (1C, Ce), 148.6 (2C, Ce), 149.4 (3C, Cf), 153.6 (3C, Cf’) Quaternary carbons at the α-position are missing. ESI-
HR m/z: calcd.exact mass for C41H27N8O2: 663.2251 [M+H]+, found: 663.2247 [M+H]+. UV-vis (CH2Cl2): λmax, nm
(log ε) 417 (5.58), 516 (4.27), 550 (3.90), 590 (3.76), 646 (3.54).
1
10-(4-nitrophenyl)-5,15,20-tris(2-pyridyl)porphyrin (10). Purple solid (102 mg, 2.6% yield). H NMR (500
MHz, CDCl3): δH,ppm -2.80 (s, 2H, NH), 7.71 (dd, J=5.1 Hz, J=6.6 Hz, 3H, Hg), 8.08 (m, 3H, Hh), 8.21 (d, J=7.6
Hz, 3H, Hg’), 8.36 (d, J=7.7 Hz, 2H, Hc), 8.61 (d, J=8.6 Hz, 2H, Hb), 8.76 (d, J=4.6 Hz, 2H, Hβ-pyrrolic), 8.87 (s, 6H,
Hβ-pyrrolic), 9.13 (d, J=4.5 Hz, 3H, Hf). 13C NMR (125 MHz, CDCl3): δC, ppm 117.6 (1C, C5), 119.1 (1C, C15), 119.2
(2C, C10 C20), 121.8 (2C, Cc), 122.5 (1C, Cf), 122.6 (2C, Cf), 130.37 (2C, Ch), 130.42 (1C, Ch), 134.9 (3C, Cf’), 135.2
(2C, Cb), 147.8 (1C, Ca), 148.67 (1C, Cg), 148.70 (2C, Cg), 149.0 (1C, Cd), 160.38 (2C, Ce), 160.40 (1C, Ce)
Quaternary carbons at the α-position are missing. ESI-HR m/z: calcd.exact mass for C41H27N8O2: 663.2251 [M+H]+,
found: 650.2247 [M+H]+. UV-vis (CH2Cl2): λmax, nm (log ε) 417 (5.49), 514 (4.25), 549 (3.81), 589 (3.80), 644
(3.43).
A2B2 porphyrins
5,10-bis(4-methoxyphenyl)-15,20-bis(4-pyridyl)porphyrin (11). Purple solid (142.2 mg, 2.9% yield). 1H NMR
(500 MHz, CDCl3): δH, ppm -2.78 (s, 2H, NH), 4.01 (s, 6H, OCH3), 7.22 (d, J=8.6 Hz, 4H, Hc), 8.06 (d, J=8.5 Hz,
4H, Hb), 8.09 (d, J=6.0 Hz, 4H, Hf), 8.76 (d, J=4.8 Hz, 2H, Hβ-pyrrolic), 8.79 (s, 2H, Hβ-pyrrolic), 8.88 (s, 2H, Hβ-pyrrolic),
8.91 (d, J=4.8 Hz, 2H, Hβ-pyrrolic), 8.96 (d, J=5.7 Hz, 4H, Hg). ESI-HR m/z: calcd.exact mass for C44H33N6O2:
677.2660 [M+H]+, found: 677.2654 [M+H]+. UV-vis (CH2Cl2): λmax, nm (log ε) 420 (5.47), 517 (4.09), 552 (3.78),
591 (3.60), 647 (3.48).
5,10-bis(3-methoxyphenyl)-15,20-bis(4-pyridyl)porphyrin (12). Purple solid (108.3 mg, 2.2% yield). 1H NMR
(500 MHz, CDCl3): δH, ppm -2.83 (s, 2H, NH), 3.97 (s, 6H, OCH3), 7.32 (dd, J3=8.3 Hz, J5=2.2 Hz, 2H, Hd), 7.62 (t,
J3=7.9 Hz, 2H, Hc), 7.79 (m, J4=1.6 Hz, J5=0.8 Hz, 4H, Hb), 8.14 (d, J3=5.6 Hz, 4H, Hf), 8.79 (d, J=4.6 Hz, 2H, Hβ-
pyrrolic), 8.83 (s, 2H, Hβ-pyrrolic), 8.92 (s, 2H, Hβ-pyrrolic), 8.95 (d, J=4.6 Hz, 2H, Hβ-pyrrolic), 9.00 (d, J3=5.5 Hz, 4H, Hg).
13C NMR (125 MHz, CDCl3): δC, ppm 55.5 (2C, OCH3), 113.7 (2C, Cd), 116.7 (2C, C15 C20), 120.6 (2C, Cb’), 121.0
(2C, C5 C10), 127.60 (2C, Cb), 127.64 (2C, Cc), 129.4 (4C, Cf), 130.7 (4C, Cβ-pyrrolic), 131.7 (4C, Cβ-pyrrolic), 143.0 (2C,
Ca), 148.3 (4C, Cg), 150.2 (2C, Ce), 158.0 (2C, Cc’) Quaternary carbons at the α-position are missing. ESI-HR m/z:
calcd.exact mass for C44H33N6O2: 677.2660 [M+H]+, found: 677.2653 [M+H]+. UV-vis (CH2Cl2): λmax, nm (log ε)
418 (5.66), 514 (4.31), 549 (3.82), 589 (3.80), 644 (3.49).
1
5,10-bis(2-methoxyphenyl)-15,20-bis(4-pyridyl)porphyrin (13). Purple solid (47.8 mg, 2.9% yield). H NMR
(500 MHz, CDCl3): δH,ppm -2.76 (s, 2H, NH), 3.58 (s, 3H, OCH3), 3.60 (s, 3H, OCH3), 7.34 (m, 4H, Hc Hc’), 7.77
(dt, J3=8.0 Hz, J4=1.6 Hz, 2H, Hd), 7.96 (dd, J3=7.2 Hz, J4=1.6 Hz, 1H, Hb), 8.00 (dd, J3=7.3 Hz, J4=1.6 Hz, 1H,
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Accepted manuscript to appear in JPP
Hb), 8.14 (m, 4H, Hf), 8.75 (d, J=4.6 Hz, 2H, Hβ-pyrrolic), 8.78 (s, 2H, Hβ-pyrrolic), 8.79 (s, 2H, Hβ-pyrrolic), 8.82 (d, J=4.3
Hz, 2H, Hβ-pyrrolic), 9.01 (m, 4H, Hg). 13C NMR (125 MHz, CDCl3): δC, ppm 55.8 (2C, OCH3), 111.0 (2C, Cc), 116.42
(1C, C15), 116.45 (1C, C20,), 117.0 (2C, C5 C10), 119.50, 119.52 (2C, Cc’), 129.4 (4C, Cf), 130.1 (2C, Cd), 130.56,
130.58 (2C, Ca), 131.5 (8C, Cβ-pyrrolic), 135.52, 135.60 (2C, Cb), 148.25 (4C, Cg), 150.4 (2C, Ce), 159.34, 159.41 (2C,
Cb’) Quaternary carbons at the β and α-position are missing. ESI-HR m/z: calcd.exact mass for C44H33N6O2:
677.2660[M+H]+, found: 648.2649 [M+H]+. UV-vis (CH2Cl2): λmax, nm (log ε) 419 (5.42), 517 (4.13), 546 (3.66),
596 (3.64), 652 (3.34).
1
5,10-bis(4-Iodophenyl)-15,20-bis(4-pyridyl)porphyrin (14). Purple solid (123 mg, 5.7% yield). H NMR (500
MHz, CDCl3): δH,ppm -2.90 (s, 2H, NH), 7.92 (d, J3=8.1 Hz, 4H, Hc), 8.10 (d, J3=8.1 Hz, 4H, Hb), 8.13 (d, J3=5.2
Hz, 4H, Hf), 8.79 (d, J3=4.6 Hz, 2H, Hβ-pyrrolic), 8.81 (s, 2H, Hβ-pyrrolic), 8.86 (s, 2H, Hβ-pyrrolic), 8.90 (d, J=4.6 Hz, 2H,
Hβ-pyrrolic), 8.95 (m, 4H, Hg). ESI-HR m/z: calcd.exact mass for C42H27I2N6: 869.0381 [M+H]+, found: 869.0378
[M+H]+. UV-vis (CH2Cl2): λmax, nm (log ε) 418 (5.63), 514 (4.27), 549 (3.85), 590 (3.74), 650 (3.62).
5,10-bis(pentafluorophenyl)-15,20-bis(4-pyridyl)porphyrin (15). Purple solid (160.4 mg, 4.0% yield). 1H
NMR (500 MHz, CDCl3): δH,ppm -2.86 (s, 2H, NH), 8.16 (d, J=5.8 Hz, 4H, Hf), 8.35 (m, 4H, Hβ-pyrrolic), 8.91 (m,
4H, Hβ-pyrrolic), 9.07 (d, J3=5.7 Hz, 4H, Hg). 13C NMR (125 MHz, CDCl3): δC, ppm 102.2 (2C, C5 C10), 119.2 (2C, C15
C20), 129.2 (4C, Cf), 131.3 (8C, Cβ-pyrrolic), 148.5 (4C, Cg), 149.4 (2C, Ce) In 13C NMR Quaternary carbons at the α-
position and pentafluorophenyl signals were not observed due to C-F coupling. ESI-HR m/z: calcd.exact mass for
C42H19F10N6: 797.1506 [M+H]+, found: 797.1490 [M+H]+. UV-vis (CH2Cl2): λmax, nm (log ε) 414 (5.56), 510 (4.30),
541 (3.50), 585 (3.78), 652 (3.12).
1
5,15-bis(4-methoxyphenyl)-10,20-bis(4-pyridyl)porphyrin (16). Purple solid (77.8 mg, 1.6% yield). H NMR
(500 MHz, CDCl3): δH, ppm -2.82 (s, 2H, NH), 4.10 (s, 6H, OCH3), 7.30 (d, J=8.5 Hz, 4H, Hc), 8.11 (d, J=8.5 Hz,
4H, Hb), 8.16 (d, J=5.4 Hz, 4H, Hf), 8.80 (d, J=4.5 Hz, 4H, Hβ-pyrrolic), 8.93 (d, J=4.4 Hz, 4H, Hβ-pyrrolic), 9.03 (d,
J=4.9 Hz, 4H, Hg). 13C NMR (125 MHz, CDCl3): δC, ppm 55.6 (2C, OCH3), 112.3 (4C, Cb), 116.4 (2C, C10 and C20),
121.3 (2C, C5 and C15), 129.4 (4C, Cf), 130.6, 131.7 (8C, Cβ-pyrrolic), 134.1 (2C, Ca), 135.6 (4C, Cc), 148.3 (4C, Cg),
150.3 (2C, Ce), 159.6 (2C, Cd) Quaternary carbons at the α-position are missing. ESI-HR m/z: calcd.exact mass for
C44H33N6O2: 677.2660 [M+H]+, found: 677.2656 [M+H]+. UV-vis (CH2Cl2): λmax, nm (log ε) 420 (5.57), 517 (4.19),
552 (3.88), 592 (3.69), 648 (3.58).
General procedure for the reduction of tripyridylporphyrin
To a solution of 5-aryl-10,15,20-trispyridylporphyrin (1.0 equiv.) in 6N HCl was added stannous chloride (1.5
equiv.) and heated at 65 °C for 2 h. After cooling down to room temperature, it was then basified with solid sodium
carbonate to pH ~ 8 and extracted with dichloromethane (3 × 50 mL). The solvent was evaporated under vaccum.
5-(4-aminophenyl)-10,15,20-tris(4-pyridyl)-17,18-dihydroporphyrin (17). The crude product mixture was
purified using preparative thin-layer chromatography (TLC) plates (CH2Cl2/MeOH, 97:3) to afford chlorin 17 (140.3
mg, 0.221 mmol) in 73% yield. 1H NMR (500 MHz, CDCl3): δH,ppm -1.35 (s, 2H, NH), 3.44 (bs, 2H, NH2), 4.13 (s,
4H, H17 H18), 6.96 (d, J=8.1 Hz, 2H, Hc), 7.83 (m, 6H, Hf, Hb), 8.03 (bs, 2H, Hf’), 8.12 (d, J=4.8 Hz, 1H, H2), 8.15 (d,
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Accepted manuscript to appear in JPP
J=4.8 Hz, 1H, H12/13), 8.32 (d, J=4.5 Hz, 1H, H8), 8.52 (d, J=4.8 Hz, 1H, H12/13), 8.55 (d, J=4.45 Hz, 1H, H7), 8.72
(d, J=4.8 Hz, 1H, H3), 9.01 (m, 6H, Hg). 13C NMR (125 MHz, CDCl3): δC, ppm 35.6 (1C, C17/C18), 35.8 (1C,
C17/C18), 109.4 (1C, C20), 109.7 (1C, C15), 113.6 (2C, Cb), 119.9 (1C, C10), 122.8 (1C, C2), 123.2 (1C, C12/C13),
125.0 (1C, C5), 127.8 (4C, Cf), 127.9 (1C, C12/C13), 129.0 (2C, Cf’), 129.3 (1C, C3), 131.4 (1C, C8), 131.5 (1C, Cd),
133.2 (1C, C7), 134.0 (1C, C11), 135.0 (2C, Cc), 136.0 (1C, C4), 139.81, 139.77 (2C, C14, C1), 146.3 (1C, Ca), 148.1
(2C, Cg’), 149.6 (4C, Cg), 150.1 (1C, Ce), 151.0 (1C, Ce), 151.1 (1C, Ce), 151.3 (1C, C9), 153.8 (1C, C6), 165.8 (1C,
C19), 166.4 (1C, C16). ESI-HR m/z: calcd.exact mass for C41H31N8: 635.2666 [M+H]+, found: 635.2661 [M+H]+.
UV-vis (CH2Cl2): λmax, nm (log ε) 420 (5.11), 518 (4.04), 548 (3.90), 598 (3.67), 653 (4.27).
5-(4-methoxyphenyl)-10,15,20-tris(4-pyridyl)-17,18-dihydroporphyrin (18). The crude product mixture was
partially purified using preparative TLC plates (CH2Cl2/MeOH, 97:3) to afford a mixture of chlorin 18 and starting
porphyrin 3 in a ratio 83:17 (28 mg). The chlorin 18 (0,036 mmol) was obtained in 46% yield. Yields and ratio of
1
compounds were determined using the integrals of the signals of pyridyl protons in 1H NMR spectrum. H NMR
(500 MHz, CDCl3): δH,ppm -1.40 (s, 2H, NH), 4.06 (s, 3H, OCH3), 4.16 (s, 4H, H17 H18), 7.23 (d, J=8.6 Hz, 2H, Hc),
7.82 (d, J=5.8 Hz, 4H, Hf), 7.99 (d, J=5.8 Hz, 2H, Hb), 8.03 (d, J=5.8 Hz, 2H, Hf’), 8.14 (d, J=4.9 Hz, 1H, H2), 8.17
(d, J=4.9 Hz, 1H, H12/13), 8.35 (d, J=4.5 Hz, 1H, H8), 8.49 (d, J=4.8 Hz, 1H, H12/13), 8.55 (d, J=4.9 Hz, 1H, H7), 8.67
(d, J=4.9 Hz, 1H, H3), 8.96 (m, 6H, Hg). 13C NMR (125 MHz, CDCl3): δC, ppm 35.7 (1C, C17/C18), 35.8 (1C,
C17/C18), 55.6 (1C, OCH3), 109.6 (1C, C20), 109.8 (1C, C15), 112.4 (2C, Cb), 120.0 (1C, C10), 123.0 (1C, C2), 123.3
(1C, C12/C13), 124.1 (1C, C5), 127.4 (4C, Cf), 127.9 (1C, C12/C13), 128.7 (2C, Cf’), 129.2 (1C, C3), 131.6 (1C, C8),
133.1 (1C, C7), 133.8 (1C, Ca), 134.1 (1C, C11), 134.9 (2C, Cc), 135.9 (1C, C4), 139.8, 139.9 (2C, C14, C1), 148.4
(2C, Cg’), 149.79, 149.81 (4C, Cg), 150.0 (1C, Ce), 151.0 (1C, Ce), 151.1 (1C, Ce), 151.5 (1C, C9), 153.6 (1C, C6),
159.6 (1C, Cd), 166.1 (1C, C19), 166.5 (1C, C16). ESI-HR m/z: calcd.exact mass for C42H32N7O: 650.2663 [M+H]+,
found: 650.2660 [M+H]+. UV-vis (CH2Cl2): λmax 420, 517, 546, 599, 653 nm.
5-(3-methoxyphenyl)-10,15,20-tris(4-pyridyl)-17,18-dihydroporphyrin (19). The crude product mixture was
partially purified using preparative TLC plates (CH2Cl2/MeOH, 97:3) to afford a mixture of chlorin 19 and starting
porphyrin 4 in a ratio 78:22 (7.3 mg, 0.011 mmol). The chlorin 19 was obtained in 34% yield. Yields and ratio of
compounds were determined using the integrals of the signals of pyridyl protons in 1H NMR spectrum. 1H NMR
(500 MHz, CDCl3): δH,ppm -1.43 (s, 2H, NH), 3.96 (s, 3H, OCH3), 4.18 (s, 4H, H17 H18), 7.29 (dd, J3=8.2 Hz,
J4=2.6 Hz, 1H, Hd), 7.60 (t, J3=7.9 Hz, 1H, Hc), 7.64 (bs, 1H, Hb’), 7.68 (d, J=7.6 Hz, 1H, Hb), 7.89 (m, 4H, Hf), 8.09
(d, J=5.2 Hz, 2H, Hf’), 8.14 (d, J=4.9 Hz, 1H, H2), 8.18 (d, J=4.9 Hz, 1H, H12/13), 8.34 (d, J=4.6 Hz, 1H, H8), 8.51 (d,
J=4.5 Hz, 1H, H12/13), 8.55 (d, J=4.7 Hz, 1H, H7), 8.70 (d, J=4.7 Hz, 1H, H3), 9.00 (m, 6H, Hg). ESI-HR m/z:
calcd.exact mass for C42H32N7O: 650.2663 [M+H]+, found: 650.2653 [M+H]+. UV-vis (CH2Cl2): λmax 417, 515, 544,
596, 653 nm.
5-(2-methoxyphenyl)-10,15,20-tris(4-pyridyl)-17,18-dihydroporphyrin (20). The crude product mixture was
purified using preparative TLC plates (CH2Cl2/MeOH, 97:3) to afford chlorin 20 (9.0 mg, 0.014 mmol) in 18%
1
yield. H NMR (500 MHz, CDCl3): δH,ppm -1.43 (s, 1H, NH), -1.41 (s, 1H, NH), 3.61 (s, 3H, OCH3), 4.16 (s, 4H,
H17 H18), 7.30 (m, 2H, Hc Hc’), 7.73 (dt, J3=8.0 Hz, J4=1.5 Hz, 1H, Hd), 7.82 (m, 4H, Hf), 7.87 (d, J3=8.3 Hz, 1H,
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Accepted manuscript to appear in JPP
Hb), 8.03 (m, 2H, Hf’), 8.13 (d, J=4.8 Hz, 1H, H2), 8.15 (d, J=4.8 Hz, 1H, H12/13), 8.33 (d, J=4.4 Hz, 1H, H8), 8.41 (d,
J=4.5 Hz, 1H, H12/13), 8.53 (d, J=4.8 Hz, 1H, H7), 8.58 (d, J=4.8 Hz, 1H, H3), 8.96 (m, 6H, Hg). 13C NMR (125
MHz, CDCl3): δC, ppm 35.73 (1C, C17/C18), 35.77 (1C, C17/C18), 55.8 (1C, OCH3), 109.66 (1C, C20), 109.69 (1C,
C15), 110.9 (1C, Cc), 119.6 (1C, Cc’),119.9 (1C, C10), 120.1 (1C, C5), 123.0 (1C, C2), 123.2 (1C, C12/C13), 127.5 (4C,
Cf), 127.6 (1C, C12/C13), 128.7 (2C, Cf’), 128.8 (1C, C3), 130.0 (1C, Cd), 130.2 (1C, Ca), 131.8 (1C, C8), 133.7 (1C,
C7), 134.0 (1C, C11), 134.9 (1C, Cb), 135.8 (1C, C4), 139.5, 139.9 (2C, C14, C1), 148.2 (2C, Cg), 149.69 (2C, Cg),
149.73 (2C, Cg), 150.1 (1C, Ce), 151.2 (2C, Ce), 151.3 (1C, C9), 153.7 (1C, C6), 159.1 (1C, Cb’), 165.9 (1C, C19),
166.2 (1C, C16). ESI-HR m/z: calcd.exact mass for C42H32N7O: 650.2663 [M+H]+, found: 650.2658 [M+H]+. UV-vis
(CH2Cl2): λmax, nm (log ε) 418 (4.95), 515 (3.86), 543 (3.63), 600 (3.88), 654 (4.21).
5-(phenyl)-10,15,20-tris(4-pyridyl)-17,18-dihydroporphyrin (21). The crude product mixture was partially
purified using preparative TLC plates (CH2Cl2/MeOH, 97:3) to afford a mixture of chlorin 21 and starting porphyrin
6 in a ratio 80:20 (25 mg). The chlorin 21 (0.040 mmol) was obtained in 34% yield. Yields and ratio of compounds
1
were determined using the integrals of the signals of pyridyl protons in 1H NMR spectrum. H NMR (500 MHz,
CDCl3): δH,ppm -1.44 (s, 2H, NH), 4.17 (s, 4H, H17 H18), 7.71 (m, 3H, Hc Hc’ Hd), 7.83 (d, J3=5.8 Hz, 4H, Hf), 8.83
(d, J3=5.8 Hz, 2H, Hf’), 8.08 (m, 2H, Hb Hb’), 8.15 (d, J=4.6 Hz, 1H, H2), 8.18 (d, J=4.9 Hz, 1H, H12/13), 8.35 (d,
J=4.6 Hz, 1H, H8), 8.45 (d, J=4.5 Hz, 1H, H12/13), 8.55 (d, J=4.8 Hz, 1H, H7), 8.63 (d, J=4.8 Hz, 1H, H3), 8.96 (m,
6H, Hg). 13C NMR (125 MHz, CDCl3): δC, ppm 35.75 (1C, C17/C18), 35.82 (1C, C17/C18), 109.73 (1C, C20), 109.86
(1C, C15), 120.0 (1C, C10), 123.1 (1C, C2), 123.3 (1C, C12/C13), 124.2 (1C, C5), 126.9 (2C, Cc Cc’), 127.4 (4C, Cf),
127.96 (1C, C7), 127.98 (1C, Cd), 128.7 (2C, Cf’), 129.1 (1C, C3), 129.4 (1C, Ca), 131.7 (1C, C8), 133.1 (1C,
C12/C13), 133.8 (2C, Cb Cb’), 134.2 (1C, C11), 135.6 (1C, C4), 139.8, 139.9 (2C, C14, C1), 148.3 (2C, Cg), 149.78 (2C,
Cg), 149.80 (2C, Cg), 150.0 (1C, Ce), 151.0 (1C, Ce), 151.1 (1C, Ce), 151.5 (1C, C9), 153.2 (1C, C6), 166.2 (1C, C19),
166.4 (1C, C16). ESI-HR m/z: calcd.exact mass for C41H30N7: 620.2557 [M+H]+, found: 620.2554 [M+H]+. UV-vis
(CH2Cl2) λmax 417, 516, 544, 599, 653 nm.
5-(4-Iodophenyl)-10,15,20-tris(4-pyridyl)-17,18-dihydroporphyrin (22). The crude product mixture was
purified using preparative TLC plates (CH2Cl2/MeOH, 97:3) to afford chlorin 22 (21.6 mg, 0.040 mmol) in 21%
1
yield. H NMR (500 MHz, CDCl3): δH,ppm -1.49 (s, 2H, NH), 4.18 (s, 4H, H17 H18), 7.80 (d, J3=8.0 Hz, 2H, Hc),
7.83 (d, J3=4.9 Hz, 4H, Hf), 8.03 (m, 4H, Hf’, Hb), 8.17 (d, J=4.8 Hz, 1H, H2), 8.19 (d, J=4.8 Hz, 1H, H12/13), 8.37 (d,
J=4.4 Hz, 1H, H8), 8.43 (d, J=4.4 Hz, 1H, H12/13), 8.56 (d, J=4.7 Hz, 1H, H7), 8.61 (d, J=4.8 Hz, 1H, H3), 8.98 (m,
6H, Hg). 13C NMR (125 MHz, CDCl3): δC, ppm 35.78 (1C, C17/C18), 35.83 (1C, C17/C18), 94.3 (1C, Cd), 109.93 (1C,
C20), 110.01 (1C, C15), 120.1 (1C, C10), 122.5 (1C, C5), 123.3 (1C, C2), 123.5 (1C, C12/C13), 127.4 (4C, Cf), 128.1
(1C, C7), 128.68 (2C, Cf’), 128.75 (1C, C3), 131.9 (1C, C8), 132.7 (1C, C12/C13), 134.3 (1C, C11), 135.1 (1C, C4),
135.4 (2C, Cc Cc’), 136.0 (2C, Cb Cb’), 139.87, 139.91 (2C, C14, C1), 141.0 (1C, Ca), 148.3 (2C, Cg), 149.8 (4C, Cg),
149.9 (1C, Ce), 150.91 (1C, Ce), 150.97 (1C, Ce), 151.6 (1C, C9), 152.6 (1C, C6), 166.4 (1C, C19), 166.6 (1C, C16).
ESI-HR m/z: calcd.exact mass for C41H29IN7: 746.1524 [M+H]+, found: 746.1522 [M+H]+. UV-vis (CH2Cl2): λmax
nm (log ε) 418 (5.19), 516 (4.08), 544 (3.87), 599 (3.63), 653 (4.42).
,
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Accepted manuscript to appear in JPP
5-(pentafluorophenyl)-10,15,20-tris(4-pyridyl)-7,8-dihydroporphyrin (23). The crude product mixture was
purified using preparative TLC plates (AcOEt/CHCl3, 1:1) to afford chlorin 23 (21.8 mg, 0.040 mmol) in 16% yield.
1H NMR (500 MHz, CDCl3): δH,ppm -1.41 (s, 1H, NH), -1.34 (s, 1H, NH), 4.23 (s, 4H, H7 H8), 7.84 (d, J3=4.9 Hz,
2H, Hf’), 8.03 (m, 4H, Hf), 8.21 (d, J=4.8 Hz, 1H, H13), 8.25 (d, J=4.7 Hz, 1H, H2), 8.39 (s, 2H, H7 H8), 8.59 (d,
J=4.7 Hz, 1H, H12), 8.64 (d, J=4.8 Hz, 1H, H3), 8.99 (m, 6H, Hg). 13C NMR (125 MHz, CDCl3): δC, ppm 35.35 (1C,
C7/C8), 35.95 (1C, C7/8), 95.5 (1C, C5), 110.5 (1C, C10), 121.14, 121.24 (2C, C15 C20), 122.4 (1C, C2), 124.1 (1C,
C13), 127.5 (2C, Cf’), 128.8 (4C, Cf), 128.9 (1C, C12), 129.2 (1C, C3), 132.7 (2C, C7/8), 134.68, 134.80 (2C, C14 C1),
140.11 (1C, C11), 140.65 (1C, C4), 148.66, 148.67 (4C, Cg), 149.7 (1C, Ce), 149.8 (1C, Ce), 150.2 (2C, Cg’), 150.7
(1C, Ce), 152.0, 152.1 (2C, C16 C19), 167.81 (1C, C9), 167.98 (1C, C6). In 13C NMR pentafluorophenyl signals were
not observed due to C-F coupling. ESI-HR m/z: calcd.exact mass for C41H25F5N7: 710.2086 [M+H]+, found:
710.2086 [M+H]+. UV-vis (CH2Cl2): λmax, nm (log ε) 416 (5.23), 514 (4.12), 542 (3.74), 600 (3.67), 655 (4.43).
5,10-bis(4-methoxyphenyl)-15,20-bis(4-pyridyl)-17,18-dihydroporphyrin (24). The crude product mixture
was purified using preparative TLC plates (CH2Cl2/MeOH, 95:5) to afford a regioisomeric mixture of 5,10-bis(4-
methoxyphenyl)-15,20-bis(4-pyridyl)-17,18-dihydroporphyrin and 5,10-bis(4-methoxyphenyl)-15,20-bis(4-pyridyl)-
1
12,13-dihydroporphyrin in a ratio 7:3 (22 mg, 0.032 mmol, 43%). H NMR (500 MHz, CDCl3): δH,ppm -1.26 (s,
2H, NH), 4.04 (s, 6H, OCH3), 4.12 (s, 4H, H17 H18), 7.21 (d, J=8.6 Hz, 4H, Hc), 7.81 (d, J=5.8 Hz, 4H, Hf), 7.99 (d,
J=8.7 Hz, 4H, Hb), 8.09 (d, J=5.1 Hz, 2H, H2 H13), 8.43 (s, 2H, H7 H8), 8.62 (d, J=4.9 Hz, 2H, H3 H12), 8.93 (m, 4H,
Hg). 13C NMR (125 MHz, CDCl3): δC, ppm 35.6 (2C, C17/C18), 55.5 (2C, OCH3), 109.0 (2C, C15 C20), 112.3 (4C, Cb),
122.5 (2C, C2 C13), 123.8 (2C, C5 C10), 127.5 (4C, Cf), 128.9 (2C, C3 C12), 132.4 (2C, C8, C7), 134.1 (2C, Ca), 134.9
(4C, Cc), 135.5 (2C, C4 C11), 139.8 (2C, C14 C1), 149.7 (4C, Cg), 151.3 (2C, Ce), 153.3 (2C, C6 C9), 159.5 (2C, Cd),
165.8 (2C, C16 C19). ESI-HRMS m/z: calcd.exact mass for C44H35N6O2: 679.2816 [M+H]+, found: 679.2808 [M+H]+.
UV-vis (CH2Cl2) λmax 420, 519, 548, 598, 652 nm.
5,10-Bis(3-methoxyphenyl)-15,20-bis(4-pyridyl)-17,18-dihydroporphyrin (25). The crude product mixture
was partially purified using preparative TLC plates (CH2Cl2/MeOH, 97:3) to afford a mixture (28 mg) of the both
regioisomeric
5,10-bis(3-methoxyphenyl)-15,20-bis(4-pyridyl)-17,18-dihydroporphyrin
and
5,10-bis(3-
methoxyphenyl)-15,20-bis(4-pyridyl)-12,13-dihydroporphyrin in a ratio 6:4 and starting porphyrin 12 in a ratio
84:16. The chlorin 25 (0.027 mmol) was obtained in 36% yield. Yields and ratio of compounds were determined
1
using the integrals of the signals of pyridyl protons in 1H NMR spectrum. H NMR (500 MHz, CDCl3): δH, ppm -
1.34 (s, 2H, NH), 3.94 (s, 6H, OCH3), 4.15 (s, 4H, H17 H18), 7.27 (dd, J3=8.6 Hz, J4=1.5 Hz, 2H, Hd), 7.58 (t, J3=7.9
Hz, 2H, Hc), 7.67 (m, 4H, Hb), 7.83 (m, 4H, Hf), 8.11 (d, J=4.8 Hz, 2H, H2 H13), 8.45 (s, 2H, H7 H8), 8.65 (d, J=4.6
Hz, 2H, H3 H12), 8.96 (m, 4H, Hg). ESI-HRMS m/z: calcd.exact mass for C44H35N6O2: 679.2816 [M+H]+, found:
679.2807 [M+H]+. UV-vis (CH2Cl2) λmax 418, 515, 545, 596, 652 nm.
5,10-Bis(2-methoxyphenyl)-15,20-bis(4-pyridyl)-17,18-dihydroporphyrin (26). The crude product mixture
was purified using preparative TLC plates (CH2Cl2/MeOH, 95:5) to afford 5,10-bis(2-methoxyphenyl)-15,20-bis(4-
pyridyl)-17,18-dihydroporphyrin (26) (11.5 mg, 0.017 mmol) in 48% yield. 1H NMR (500 MHz, CDCl3): δH, ppm -
1.30 (s, 2H, NH), 3.59 (s, 3H, OCH3), 3.61 (s, 3H, OCH3), 3.94 (s, 6H, OCH3), 4.13 (s, 4H, H17 H18), 7.27 (m, 4H,
13

Accepted manuscript to appear in JPP
Hc Hc’), 7.70 (dt, J3=8.0 Hz, J4=1.6 Hz, 2H, Hd), 7.82 (m, 4H, Hf), 7.85 (dd, J3=7.5 Hz, J4=1.7 Hz, 1H, Hb), 7.88 (dd,
J3=7.2 Hz, J4=1.4 Hz, 1H, Hb), 8.07 (d, J=4.8 Hz, 2H, H2 H13), 8.33 (s, 2H, H7 H8), 8.52 (d, J=4.6 Hz, 2H, H3 H12),
8.94 (d, J=4.8 Hz, 4H, Hg). 13C NMR (125 MHz, CDCl3): δC, ppm 35.6 (2C, C17/C18), 55.8 (2C, OCH3), 109.05
109.07 (2C, C15 C20), 110.9 (2C, Cb), 119.43, 119.46 (2C, Cc’), 119.7 (2C, C2 C13), 122.45, 122,47 (2C, C5 C10),
127.6 (4C, Cf), 128.17, 128.20 (2C, C3 C12), 129.8 (2C, Cd), 130.55, 130.57 (2C, Ca), 132.20, 132.22 (2C, C8, C7),
134.88, 134.95 (2C, Cc), 135.30, 135.31 (2C, C4 C11), 139.5 (2C, C14 C1), 149.6 (4C, Cg), 151.5 (2C, Ce), 153.3 (2C,
C6 C9), 159.14, 159,20 (2C, Cd), 165.3 (2C, C16 C19). ESI-HRMS m/z: calcd.exact mass for C44H35N6O2: 679.2816
[M+H]+, found: 679.2811 [M+H]+. UV-vis (CH2Cl2): λmax, nm (log ε) 418 (4.94), 515 (3.89), 541 (3.71), 599 (3.45),
653 (4.23).
5,10-Bis(4-iodophenyl)-15,20-bis(4-pyridyl)-17,18-dihydroporphyrin (27). The crude product mixture was
purified using preparative TLC plates (CH2Cl2/MeOH, 97:3) to afford a regioisomeric mixture of 5,10-bis(4-
iodophenyl)-15,20-bis(4-pyridyl)-17,18-dihydroporphyrin and 5,10-bis(4-iodophenyl)-15,20-bis(4-pyridyl)-12,13-
dihydroporphyrin in a ratio 55:45 (12.5 mg, 0.012 mmol, 45%). 1H NMR (500 MHz, CDCl3): δH,ppm -1.43 (s, 2H,
NH), 4.16 (s, 4H, H17 H18), 7.79 (d, J=8.0 Hz, 4H, Hc), 7.82 (m, 4H, Hf), 8.02 (d, J=8.1 Hz, 4H, Hb), 8.14 (d, J=4.6
Hz, 2H, H2 H13), 8.39 (s, 2H, H7 H8), 8.59 (d, J=4.6 Hz, 2H, H3 H12), 8.97 (m, 4H, Hg). ESI-HRMS m/z: calcd.exact
mass for C42H29I2N6: 871.0538 [M+H]+, found: 871.0535 [M+H]+. UV-vis (CH2Cl2): λmax, nm (log ε) 419 (5.13),
517 (4.00), 545 (3.82), 599 (3.56), 653 (4.31).
5,10-bis(pentafluorophenyl)-15,20-bis(4-pyridyl)-7,8-dihydroporphyrin
(28)
and
5,10-
bis(pentafluorophenyl)-15,20-bis(4-pyridyl)-2,3,7,8-tetrahydroporphyrin (29). The crude product mixture was
purified using preparative TLC plates (CH2Cl2/Ethyl acetate 5/5) to afford a mixture (10.2 mg) of 5,10-
bis(pentafluorophenyl)-15,20-bis(4-pyridyl)-7,8-dihydroporphyrin 28 (0.010 mmol, 9.6%) and 5,10-
bis(pentafluorophenyl)-15,20-bis(4-pyridyl)-2,3,7,8-tetrahydroporphyrin 29 (0.003 mmol, 3.2%).
28: 1H NMR (500 MHz, CDCl3): δH,ppm -1.21 (s, 2H, NH), 4.26 (s, 4H, H7 H8), 8.04 (d, J=5.0 Hz, 4H, Hf), 8.23
(d, J=4.7 Hz, 2H, H2 H13), 8.35 (s, 2H, H17 H18), 8.62 (d, J=4.8 Hz, 2H, H3 H12), 8.97 (d, J=4.4 Hz, 4H, Hg). 13C
NMR (125 MHz, CDCl3): δC, ppm 35.0 (2C, C7 C8), 95.4 (2C, C5 C10), 121.7 (2C, C15 C20), 122.4 (2C, C2 C13), 128.6
(4C, Cf), 129.40 (2C, C3 C12), 132.6 (2C, C17 C18), 134.6 (2C, C1 C14), 140.5 (2C, C4 C11), 148.3 (4C, Cg), 149.5 (2C,
Ce), 152.0 (2C, C16 C19), 168.6 (2C, C6 C9). In 13C NMR pentafluorophenyl signals were not observed due to C-F
coupling. ESI-HRMS m/z: calcd.exact mass for C42H21F10N6: 799.1663 [M+H]+, found: 799.1659 [M+H]+.
29: 1H NMR (500 MHz, CDCl3): δH,ppm 3.35 (s, 4H, Hβ-pyrrolic), 3.40 (s, 4H, Hβ-pyrrolic), 6.87 (d, J=4.5 Hz, 1H, Hβ-
pyrrolic), 6.93 (d, J=4.4 Hz, 1H, Hβ-pyrrolic), 7.35 (d, J=4.5 Hz, 1H, Hβ-pyrrolic), 7.40 (d, J=4.5 Hz, 1H, Hβ-pyrrolic), 7.55 (d,
J=4.2 Hz, 2H, Hf), 7.70 (d, J=4.9 Hz, 2H, Hf), 8.80 (d, J=3.8 Hz, 4H, Hg). ESI-HRMS m/z: calcd.exact mass for
C42H23F10N6: 801.1819 [M+H]+, found: 801.1780 [M+H]+.
5,10,15,20-tetra(4-pyridyl)-2,3-dihydroporphyrin
(30),
5,10,15,20-tetra(4-pyridyl)-2,3,12,13-
tetrahydroporphyrin (31) and 5,10,15,20-tetra(4-pyridyl)-2,3,17,18-tetrahydroporphyrin (32).
30: 1H NMR (500 MHz, CDCl3): δH,ppm -1.56 (s, 2H, NH), 4.20 (s, 4H, H2 H3), 7.84 (d, J=5.7 Hz, 4H, Hf), 8.04
(d, J=5.7 Hz, 4H, Hf), 8.22 (d, J=4.7 Hz, 2H, H7 H18), 8.40 (s, 2H, H12 H13), 8.59 (d, J=4.8 Hz, 2H, H8 H17), 8.97 (d,
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Accepted manuscript to appear in JPP
J=4.7 Hz, 4H, Hg), 8.98 (d, J=5.0 Hz, 4H, Hg). 13C NMR (125 MHz, CDCl3): δC, ppm 35.9 (2C, C2 C3), 110.3 (4C,
Cmeso), 123.7 (2C, C7 C18), 127.4 (4C, Cf), 128.2 (2C, C8 C17), 128.7 (4C, Cf), 132.3 (2C, C12 C13), 134.5 (2C, C9 C16),
139.9 (2C, C6 C19), 148.3 (4C, Cg), 149.80 (4C, Cg), 149.84 (2C, Ce), 150.8 (2C, Ce), 151.7 (2C, C11 C14), 166.8 (2C,
C1 C4). ESI-HRMS m/z: calcd.exact mass for C40H29N8: 621.2510 [M+H]+, found: 621.2501 [M+H]+. UV-vis
(CH2Cl2): λmax, nm (log ε) 417 (5.15), 516 (4.03), 543 (3.71), 599 (3.54), 654 (4.31).
31: 1H NMR (500 MHz, CDCl3/MeOD 9:1): δH,ppm 4.01 (s, 8H, Hβ-pyrrolic), 7.82 (d, J=5.9 Hz, 8H, Hf), 7.95 (s,
4H, Hβ-pyrrolic), 8.90 (d, J=5.9 Hz, 8H, Hg).
32: 1H NMR (500 MHz, CDCl3/MeOD 9:1): δH,ppm 3.32 (m, 8H, Hβ-pyrrolic), 6.90 (d, J=4.6 Hz, 2H, Hβ-pyrrolic),
7.36 (d, J=4.4 Hz, 2H, Hβ-pyrrolic), 7.48 (d, J=6.0 Hz, 2H, Hf), 7.58 (d, J=6.1 Hz, 4H, Hf), 7.74 (d, J=6.0 Hz, 2H, Hf),
8.77 (m, 8H, Hg). ESI-HRMS m/z: calcd.exact mass for C40H31N8: 623.2666 [M+H]+, found: 623.2664 [M+H]+.
5-(4-aminophenyl)-10,15,20-tris(3-pyridyl)porphyrin (9NH2). Purple solid (92 mg, 97% yield). 1H NMR (500
MHz, CDCl3): δH,ppm -2.75 (s, 2H, NH), 3.98 (s, 2H, NH2), 6.99 (d, J=8.3 Hz, 2H, Hc), 7.70 (dd, J=5.3 Hz, J=7.2
Hz, 3H, Hg), 7.95 (d, J=8.0 Hz, 2H, Hb), 8.50 (d, J=7.4 Hz, 3H, Hf), 8.79 (d, J=4.6 Hz, 2H, Hβ-pyrrolic), 8.84 (s, 4H,
Hβ-pyrrolic), 9.01 (d, J=4.6 Hz, 2H, Hβ-pyrrolic), 9.03 (dd, J=4.9 Hz, J=1.2 Hz, 3H, Hh), 9.47 (s, 3H, Hf’). δC, ppm 113.6
(2C, Cb), 115.9 (1C, C15), 116.4 (2C, C10 C20), 122.2 (3C, Cg), 122.5 (1C, C5), 131.1 (6C, Cβ-pyrrolic), 131.8 (1C, Ca),
132.3 (2C, Cβ-pyrrolic), 136.0 (2C, Cc), 138.0 (1C, Ce), 138.1 (2C, Ce), 141.1 (3C, Cf), 146.6 (1C, Cd), 149.3 (3C, Ch),
153.8 (3C, Cf’) Quaternary carbons at the α-position are missing. ESI-HR m/z: calcd.exact mass for C41H29N7:
633.2510 [M+H]+, found: 633.2507 [M+H]+. UV-vis (CH2Cl2): λmax, nm (log ε) 420 (5.16), 518 (3.86), 555 (3.61),
593 (3.37), 650 (3.30).
5-(4-aminophenyl)-10,15,20-tris(2-pyridyl)-17,18-dihydroporphyrin (33). The crude product mixture was
purified using preparative TLC plates (CH2Cl2/MeOH, 97:3) to afford chlorin 33 (51.5 mg, 0.081 mmol) in 54%
1
yield. H NMR (500 MHz, CDCl3): δH,ppm -1.27 (s, 2H, NH), 4.20 (bs, 6H, NH2 H17 H18), 6.98 (d, J=8.3 Hz, 2H,
Hc), 7.57 (m, 2H, Hg), 7.62 (m, 1H, Hg), 7.87 (m, 4H, Hb Hg’), 8.01 (m, 3H, Hh), 8.11 (m, 2H, Hg’ H2), 8.15 (d, J=4.9
Hz, 1H, H12/13), 8.33 (d, J=4.5 Hz, 1H, H8), 8.51 (d, J=4.5 Hz, 1H, H7), 8.57 (d, J=4.9 Hz, 1H, H12/13), 8.68 (d, J=4.8
Hz, 1H, H3), 9.01 (m, 2H, Hf), 9.05 (d, J=4.8 Hz, 1H, Hf). 13C NMR (125 MHz, CDCl3): δC, ppm 34.8 (1C, C17/C18),
35.1 (1C, C17/C18), 111.1 (1C, C20), 111.3 (1C, C15), 113.5 (2C, Cb), 121.0 (1C, C10), 122.2 (1C, C2), 122.3 (3C, Cg),
123.1 (1C, C12/C13), 124.3 (1C, C5), 127.89, 127.97, 128.04 (3C, Cg’ C12/C13), 128.7 (1C, C3), 129.6, (1C, Cg’), 131.1
(1C, C8), 132.2 (1C, Cd), 132.7 (1C, C7), 134.7 (1C, C11), 134.8 (1C, C4), 135.1 (2C, Cc), 135.6 (1C, Ch), 136.0 (2C,
Ch), 140.4, 140.6 (2C, C14, C1), 146.0 (1C, Ca), 148.5 (1C, Cf), 149.26, 149.28 (2C, Cf), 152.0 (1C, C9), 153.1 (1C,
C6), 160.7 (1C, Ce), 161.5 (1C, Ce), 161.7 (1C, Ce), 166.9 (1C, C19), 167.8 (1C, C16). ESI-HR m/z: calcd.exact mass
for C41H31N8: 635.2666 [M+H]+, found: 635.2660 [M+H]+. UV-vis (CH2Cl2): λmax, nm (log ε) 422 (5.09), 518
(3.99), 548 (3.81), 598 (3.58), 653 (4.28).
Functionalization of 5-(4-aminophenyl)-10,15,20-tris(4-pyridyl)-17,18-dihydroporphyrin (17)
5-(4-azidophenyl)-10,15,20-tris(4-pyridyl)-17,18-dihydroporphyrin (34). 5-(4-aminophenyl)-10,15,20-tris(4-
pyridyl)-17,18-dihydroporphyrin (17) (121.7 mg, 0.192 mmol) was dissolved in trifluoroacetic acid (1.2 mL) and
15

Accepted manuscript to appear in JPP
cooled at 0 ˚C. A solution of sodium nitrite (27.5 mg, 0.40 mmol) in water (0.5 mL) was added dropwise. The
mixture was stirred for 15 minutes at 0 ˚C before adding dropwise a solution of sodium azide (51.3 mg, 0.79 mmol)
in water (0.5 mL). The reaction mixture was stirred at 0 ˚C for 1 hour. The mixture was diluted with water and
neutralized with saturated sodium bicarbonate solution. The aqueous mixture was extracted three times with
chloroform (3 x 20 mL), and the organic layer dried over magnesium sulfate. The solvent was removed under
reduced pressure. The crude was purified by column chromatography (CH2Cl2/MeOH, 97:3) to afford chlorin 34
(33.3 mg, 0.050 mmol) in 26% yield. 1H NMR (500 MHz, CDCl3): δH,ppm -1.44 (s, 2H, NH), 4.17 (s, 4H, H17 H18),
7.34 (d, J=8.0 Hz, 2H, Hc), 7.81 (m, 4H, Hf’), 8.03 (d, J=5.5 Hz, 2H, Hf’), 8.05 (d, J=8.5 Hz, 2H, Hb), 8.17 (d, J=5.0
Hz, 1H, H2), 8.19 (d, J=5.0Hz, 1H, H12/13), 8.36 (d, J=4.5 Hz, 1H, H8), 8.44 (d, J=4.0 Hz, 1H, H12/13), 8.56 (d, J=4.5
Hz, 1H, H7), 8.62 (d, J=4.5 Hz, 1H, H3), 8.96 (m, 6H, Hg). ESI-HR m/z: calcd.exact mass for C41H29N10: 661.2571
[M+H]+, found: 661.2572 [M+H]+. UV-vis (CH2Cl2): λmax, nm (log ε) 418 (5.35), 518 (4.22), 543 (4.01), 599 (3.75),
653 (4.49).
Compound 35. 5-(4-aminophenyl)-10,15,20-tris(4-pyridyl)-17,18-dihydroporphyrin (17) (53.6 mg, 0.084 mmol)
was dissolved in dry dichloromethane (7 mL). Glutaric anhydride (18 mg, 1.58 mmol) was added. The mixture was
stirred for 20h at room temperature. The solvent was removed under reduced pressure. The crude product mixture
was purified using preparative TLC plates (CH2Cl2/MeOH, 95:5) to afford chlorin 35 (49.2 mg, 0.065 mmol) in 77%
yield. 1H NMR (500 MHz, CDCl3/MeOD 9:1): δH,ppm -1.43 (s, 2H, NH), 2.16 (quin, J=7.0 Hz, 2H, CH2), 2.55 (t,
J=6.9 Hz, 2H, CH2), 2.60 (t, J=7.4 Hz, 2H, CH2), 3.40 (m, 1H, NH), 4.16 (s, 4H, H17 H18), 7.87 (d, J=4.6 Hz, 2H,
Hf), 7.88 (d, J=4.5 Hz, 2H, Hf), 7.92 (d, J=8.2 Hz, 2H, Hc), 8.02 (d, J=8.2 Hz, 2H, Hb), 8.07 (d, J=5.7 Hz, 2H, Hf’),
8.13 (d, J=4.8 Hz, 1H, H2), 8.17 (d, J=4.9 Hz, 1H, H12/13), 8.32 (d, J=4.7 Hz, 1H, H8), 8.49 (d, J=4.4 Hz, 1H, H12/13),
8.54 (d, J=4.8 Hz, 1H, H7), 8.68 (d, J=4.7 Hz, 1H, H3), 8.93 (m, 6H, Hg). 13C NMR (125 MHz, CDCl3/MeOD 9:1):
δC, ppm 21.1 (1C, CH2), 33.2 (1C, CH2), 35.8 (1C, C17/C18), 35.9 (1C, C17/C18), 36.5 (1C, CH2), 109.5 (1C, C20),
109.7 (1C, C15), 118.2 (2C, Cb), 119.8 (1C, C10), 123.1 (1C, C2), 123.4 (1C, C12/C13), 124.1 (1C, C5), 127.8 (4C, Cf),
128.0 (1C, C12/C13), 129.0 (2C, Cf’), 129.3 (1C, C3), 131.7 (1C, C8), 133.2 (1C, C7), 133.9 (1C, C11), 134.4 (2C, Cc),
135.6 (1C, C4), 136.9 (1C, Cd), 138.4 (1C, Ca), 139.64, 139.74 (2C, C14, C1), 147.66 (2C, Cg’), 149.10 (2C, Cg),
149.16 (2C, Cg), 150.9 (1C, Ce), 151.4 (1C, Ce), 151.8 (1C, Ce), 152.0 (1C, C9), 153.4 (1C, C6), 166.8 (1C, C19),
166.5 (1C, C16), 171.9 (1C, C=O), 176.2 (1C, C=O). ESI-HR m/z: calcd.exact mass for C46H37N8O3: 749.2983
[M+H]+, found: 749.2979 [M+H]+. UV-vis (CH2Cl2): λmax, nm (log ε) 419 (4.98), 517 (3.84), 545 (3.69), 599 (3.43),
653 (4.12).
Compound 36. A solution of (3-carboxypropyl)triphenylphosphonium bromide (202 mg, 0.471 mmol) in
dichloromethane (5 mL) was cooled to 0 °C. Triethylamine (0.077 mL, 0.552 mmol) and ethylchloroformate (0.054
mL, 0.565 mmol) were added. The reaction mixture was stirred for 30 min and then transferred to a solution in
another flask containing 5-(4-aminophenyl)-10,15,20-tris(4-pyridyl)-17,18-dihydroporphyrin (17) (45 mg, 0.071
mmol) dissolved in dichloromethane (5 mL) and triethylamine (0.077 mL, 0.552 mmol) at 0 °C. Stirring was
continued for 1 h at the same temperature and allowed to reach at room temperature for another 1 h. After
completion of the reaction, water (5 mL) was added into the reaction mixture and basified to pH ~ 8 with sodium
16

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carbonate and extracted with chloroform (3 × 25 mL). The solvent was evaporated and purified on a silica gel
1
column chromatography (CH2Cl2/MeOH, 94:6) to produce compound 36 (35 mg, 0,034 mmol) in 48% yield. H
NMR (500 MHz, CDCl3): δH, ppm -1.42 (s, 2H, NH), 2.21 (m, 2H, CH2), 3.21 (m, 2H, CH2CO), 3.82 (t, J=16.2
Hz, 2H, CH2P), 4.16 (s, 4H, H17 H18), 7.76 (m, 6H, HPh), 7.84 (m, 13H, HPh Hf’), 7.99 (d, J=8.2 Hz, 2H, Hb), 8.03 (d,
J=4.8 Hz, 2H, Hf), 8.12 (d, J=4.6 Hz, 1H, H2), 8.16 (d, J=4.5 Hz, 1H, H12/13), 8.25 (d, J=8.4 Hz, 2H, Hc), 8.32 (d,
J=4.4 Hz, 1H, H8), 8.52 (d, J=4.6 Hz, 1H, H7), 8.53 (d, J=5.1 Hz, 1H, H12/13), 8.69 (d, J=4.8 Hz, 1H, H3), 8.96 (m,
6H, Hg), 10.83 (s, 1H, NH). 13C NMR (125 MHz, CDCl3): δC, ppm 19.8 (1C, CH2), 22.0 (d, 1C, CH2P), 35.71 (1C,
C17/C18), 35.77 (1C, C17/C18), 37.2 (d, 1C, CH2CO), 109.5 (1C, C20), 109.7 (1C, C15), 118.0 (d, 3C, CPh), 118.5 (2C,
Cc), 119.8 (1C, C10), 123.0 (1C, C2), 123.1 (1C, C12/C13), 124.4 (1C, C5), 127.5 (4C, Cf’), 127.8 (1C, C12/C13), 128.7
(2C, Cf), 129.4 (1C, C3), 130.7, 130.8 (6C, CPh), 131.6 (1C, C8), 133.3 (1C, C7), 133.5, 133.6 (6C, CPh), 134.0 (1C,
C11), 134.2 (2C, Cb), 135.3 (3C, CPh), 135.8 (1C, C4), 136.5 (1C, Cd), 139.0 (1C, Ca), 139.7, 139.9 (2C, C14, C1),
148.2 (2C, Cg), 149.66 (2C, Cg’), 149.70 (2C, Cg’), 150.2 (1C, Ce), 151.16 (1C, Ce), 151.24 (1C, Ce), 151.37 (1C,
C9), 153.5 (1C, C6), 166.0 (1C, C19), 166.3 (1C, C16), 171.2 (1C, C=O). ESI-HR m/z: calcd.exact mass for
C63H50N8OP: 965.3840 [M]+, found: 965.3833 [M]+. UV-vis (CH2Cl2): λmax, nm (log ε) 420 (5.28), 517 (4.12), 545
(3.96), 599 (3.69), 653 (4.40).
Compound 37. To a solution of compound 36 (16 mg, 0.015 mmol) in dry DMF (1.5 mL) was added methyl
iodide (0.187 mL, 3.004 mmol). The reaction mixture was stirred for 24 h at 40 °C. The product was precipitated by
addition of a large excess of diethyl ether. It was then filtered and washed well with diethyl ether to afford the
chlorin derivative 37 as a brown solid (13 mg, 0.009 mmol) in 60% yield. 1H NMR (500 MHz, DMSO-d6): δH, ppm
-1.29 (s, 2H, NH), 1.96 (m, 2H, CH2), 2.78 (m, 2H, CH2CO), 3.73 (m, 2H, CH2P), 4.28 (s, 4H, H17 H18), 4.63 (s,
6H, HMe), 4.66 (s, 3H, HMe), 7.83 (m, 6H, HPh), 7.92 (m, 13H, HPh Hf’), 8.11 (d, J=8.5 Hz, 2H, Hb), 8.17 (d, J=8.2
Hz, 2H, Hc), 8.42 (s, 2H, H12/13), 8.43 (d, J=5.2 Hz, 1H, H8), 8.54 (d, J=5.9 Hz, 1H, H2), 8.71 (d, J=5.2 Hz, 1H, H7),
8.75 (m, 4H, Hf), 8.83 (d, J=6.5 Hz, 2H, Hf), 8.88 (d, J=5.9 Hz, 1H, H3), 9.38 (m, 6H, Hg), 10.46 (s, 1H, NH). 13C
NMR (125 MHz, DMSO-d6): δC, ppm 18.1 (1C, CH2), 20.1 (d, 1C, CH2P), 35.58 (1C, C17/C18), 35.83 (1C, C17/C18),
36.1 (d, 1C, CH2CO), 47.9 (3C, CH3), 107.7 (1C, C20), 107.9 (1C, C15), 117.4 (1C, C10), 117.7 (4C, Cc Cd C5), 118.4
(d, 3C, CPh), 123.6 (1C, C8), 124.3 (1C, C2), 129.1 (1C, C3), 129.8 (1C, C7), 130.2, 130.3 (6C, CPh), 131.0 (4C, Cf’),
131.4 (2C, Cf), 131.8 (1C, C12/C13), 133.1 (1C, C4), 133.3 (1C, C12/C13), 133.59, 133.67 (6C, CPh), 133.9 (2C, Cb),
135.0 (3C, CPh), 135.1 (1C, C9), 139.0 (1C, C6), 139.20 (1C, Ca), 139.29 (1C, C1), 144.2 (2C, Cg), 145.4 (4C, Cg),
150,0, 152.8 (2C, C11 C14), 156.5 (1C, Ce), 157.7 (1C, Ce), 157.9 (1C, Ce), 167.1 (1C, C19), 168.0 (1C, C16), 170.2
(1C, C=O). ESI-HR m/z: calcd.exact mass for C66H59N8OP: 252.6132 [M]4+, found: 252.6139 [M]4+. UV-vis
(MeOH): λmax, nm (log ε) 426 (5.11), 518 (4.08), 550 (3.97), 607 (3.66), 661 (4.33). UV-vis (H2O): λmax, nm (log ε)
423 (4.47), 521 (3.34), 553 (3.2), 602 (2.93), 655 (3.54).
CONCLUSION
In summary, we have developed a one-step reduction method of porphyrins substituted with two, three or four 2-
or 4-pyridyls to corresponding dihydroporphyrins. The reduction of 5-(aryl)-10,15,20-tris(2 or 4-pyridyl)porphyrin
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with tin(II) chloride dihydrate demonstrated good regioselectivity. Porphyrin with one meso-aryl substituted with
electron-donating groups gave 5-aryl-10,15,20-tris(2- or 4-pyridyl)-17,18-dihydroporphyrins in 17-72% yield.
Porphyrin with one meso-aryl substituted with electron-withdrawing groups gave 5-aryl-10,15,20-tris(4-pyridyl)-
17,18-dihydroporphyrins or 5-aryl-10,15,20-tris(4-pyridyl)-7,8-dihydroporphyrins in 15-21% yield and
isobacteriochlorin. It would seem that the reduction occurs on the more electron deficient pyrrole unit. We assumed
that protonated 2- or 4-pyridyl substituents play an essential role in the reaction by stabilizing the reaction
intermediate. We have also proved the possibility to functionalize these compounds to design new regioisomerically
pure photosensitizers.
Acknowledgments:
We thank Dr. Cyril Colas for ESI-HRMS analyses. The regional council of Nouvelle-Aquitaine is acknowledged
for financial support.
Supporting Information:
Supplementary material is available via the Internet at http://www.u-bourgogne.fr/jpp/.
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[a]
[b]
Table 1. Results from various porphyrin reduction using Tin(II) chloride. Presence of a single regioisomer.
Presence of
residual starting porphyrin. Yields were determined by 1H NMR analysis of the partially purified reaction mixture. [c] Presence of
two regioisomers. Regioisomeric ratio was calculated from the integrals of the β-pyrrolic protons.
[d]
Presence of
isobacteriochlorin. Yields of chlorin were determined by 1H NMR analysis.
Substituents
Porphyrin
Chlorin
18[a][b]
yield
R1
R2
R3
R4
46%
3
4
19[a][b]
34%
17%
20[a]
5
A3B
21[a][b]
22[a] [d]
34%
21%
6
7
23[a] [d]
16%
8
24[b] [c]
25[b] [c]
43% 7:3 r.r.
11
12
36%
6:4 r.r.
26[a]
27[b]
48%
13
14
Cis-A2B2
45% 5.5:4.5
r.r.
28[a][d]
10%
15%
15
1
A4
30
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Scheme 1. Synthesis of porphyrins bearing pyridyls and aryls substituents
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Scheme 2. Synthesis of chlorin 17 and assignments based on the results obtained from the 2D NOESY NMR studies in CDCl3.
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Scheme 3. Proposition of mechanistic pathway for the reduction of porphyrin
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Scheme 4. Reagents and conditions: (a) TFA, NaNO2, H2O, NaN3, H2O; (b) glutaric anhydride, CH2Cl2
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Scheme 5. Reagents and conditions: (a) ClCOOEt, TEA, CH2Cl2; (b) excess CH3I, DMF
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Figure 1. 2D NOESY NMR spectrum of compound 17 in CDCl3
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Figure 2. 13C NMR spectrum of compound 17 in CDCl3
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Figure 3. Average effect of temperature, reaction time, HCl concentration and SnCl2.2H2O equivalent on yield of chlorin 17 and
porphyrin 2NH2
29