Isomers of β,β-Dinitro-5,10,15,20-tetraphenylporphy-rin Derivatives: Valuable starting materials for further transformations

Article abstract of DOI:10.3390/molecules24050838

The synthesis, chromatographic isolation, and structure elucidation of β,β-substituted isomers of dinitro-5,10,15,20-tetraphenylporphyrin complexes are described. meso-Tetraphenyl-porphyrin chelates (Cu^II, Ni^II, Co^II) upon reaction wit e.g., itric acid (yellow HNO₃, d = 1.52, diluted to 25–50%) in CHCl₃ formed a mixture of nitro-derivatives with combined yields of ca 80%. This nitration (under optimized conditions: 25–30% HNO₃, 30–40 min, r.t.) can be carried out selectively to give mainly β,β-dinitro-compounds in yields of up to 73%. From the above mixtures of five possible regioisomers that can be formed, usually two or three of them were isolated, for which the structures were assigned on the basis of ¹H NMR spectra including COSY and NOESY measure-ments. These types of products are attractive starting materials for synthesis of potential anticancer PDT agents with unique structures, being practically unavailable by any other alternative method.

Full text of DOI:10.3390/molecules24050838

molecules
Article
Isomers of
β,β-Dinitro-5,10,15,20-tetraphenylporphy-rin
Derivatives: Valuable Starting Materials for
Further Transformations
Agnieszka Mikus * , Mariusz Rosa and Stanisław Ostrowski
Faculty of Chemistry, Warsaw University of Technology, ul. Noakowskiego 3, 00-664 Warszawa, Poland;
mariuszrosa1@gmail.com (M.R.); stan@ch.pw.edu.pl (S.O.)
* Correspondence: a.mikus@ch.pw.edu.pl; Tel.: +48-22-234-5063
ꢀꢁꢂꢀꢃꢄꢅꢆꢇ
Academic Editors: M. Graça P. M. S. Neves, M. Amparo F. Faustino and Nuno M. M. Moura
Received: 10 January 2019; Accepted: 19 February 2019; Published: 27 February 2019
ꢀꢁꢂꢃꢄꢅꢆ
Abstract: The synthesis, chromatographic isolation, and structure elucidation of
β
,
β
-substituted isomers
of dinitro-5,10,15,20-tetraphenylporphyrin complexes are described. meso-Tetraphenyl-porphyrin
chelates (CuII, NiII, CoII) upon reaction wit e.g., itric acid (yellow HNO3, d = 1.52, diluted to 25–50%)
in CHCl3 formed a mixture of nitro-derivatives with combined yields of ca 80%. This nitration
(under optimized conditions: 25–30% HNO3, 30–40 min, r.t.) can be carried out selectively to give
mainly β,β-dinitro-compounds in yields of up to 73%. From the above mixtures of five possible
regioisomers that can be formed, usually two or three of them were isolated, for which the structures
were assigned on the basis of 1H NMR spectra including COSY and NOESY measure-ments. These
types of products are attractive starting materials for synthesis of potential anticancer PDT agents
with unique structures, being practically unavailable by any other alternative method.
Keywords: porphyrins; complexes; β-nitration; electrophilic substitution; nitric acid; 2D NMR.
1. Introduction
A number of porphyrin derivatives are of significant importance due to their potential use in
many fields of chemistry, medicine, pharmacology, new materials, etc. [1]. The desired precursors for
the synthesis of these compounds can be isolated from naturally occurring substances (e.g., chlorophyll,
heme) or prepared via transformations of simple synthetic moieties (e.g., meso-tetraphenylporphyrin,
TPP). Thus, nowadays the selective functionalization of porphyrins is being studied intensively.
Recently, successful nitration of TPP zinc complex 1a (Scheme 1), leading mainly to
[2,7-dinitro-5,10,15,20-tetraphenylporphyrinato]zinc(II) as the major product with a satisfactory yield
ca 40%, has been demonstrated [
materials for our ongoing projects; e.g., (a) an exhaustive substitution at all
neighbouring pyrrole rings (which allows the synthesis of highly substituted porphyrins) [
2
]. The respective dinitroporphyrins of this type are valuable starting
-positions in two
] or
], etc. They could also serve as
β
3
(b) controlled cycloaddition reactions leading to isobacteriochlorins [
4
interesting models for electrochemical studies [5].
Thus, we have attempted to elaborate the dinitration reaction for some additional TPP chelates
(CuII, NiII, CoII), in search for other
-dinitro-isomers. Such a nitration of a copper complex has
been already reported. Dahal et al. observed mixtures of two or three dinitro-compounds in various
reactions [ ]. However, the total yields were relatively low (ca 20%) and no information was provided
β,β
6
about the yields of individual isolated isomers. The resulting NO2-disubstituted porphyrins could be
very attractive intermediates for synthesis of the target moieties of higher complexity, e.g., potential
anticancer agents [7–11].
Molecules 2019, 24, 838; doi:10.3390/molecules24050838
www.mdpi.com/journal/molecules

Molecules 2019, 24, 838
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NO2
Ph
Ph
M
HNO3i) / CHCl3, r.t.,ii) 30-40 min,
under argon
N
N
N
N
N
N
N
N
M
dinitro-isomers
Ph
+
Ph
Ph
Ph
then, column chromatography
3
a: 40%iii) c: 56%
b: 30-64% d: 73%
Ph
Ph
2
1
a: not isolated
b: < 5%
a: M = Zn
b: M = Co
c: M = Cu
d: M = Ni
preparative
TLC
(for M = Cu, Ni)
c: 28%
d: 6.5%
Ph NO2
Ph
Ph NO2
NO2
N
N
N
N
N
N
N
N
N
N
N
M
+
M
M
+
Ph
Ph
Ph others
+
Ph
Ph
Ph
N
NO2
NO2
Ph
Ph
Ph NO2
i)
25-30% for 1c, 1d;
1-5% for 1b
2,7-dinitro-
3ca, 15%
3da, 22%
3,7-dinitro-
3cb, 13%
3db, 22%
2,8-dinitro-
3cc, ca 10%
3dc,
ii)
0-5oC for 1b
iii) data from lit. [2]
H2SO4 / CF3CO2H
3ca-3cc,
3da-3db
4a-c
NO2
NO2
NO2
Ph
Ph
Ph
Ph
NO2
Ph
NO2
NH
N
N
NH
N
NH
N
NH
N
N
N
N
NH
N
N
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
HN
HN
HN
HN
HN
NO2
NO2
O2N
Ph
Ph
Ph NO2
O2N
Ph
Ph
4a
4b
4c
4d
4e
Scheme 1. Preparation of dinitro-isomers and all the possible structures of the products.
2. Results and Discussion
Three TPP complexes (CuII, NiII, CoII) were used for our investigations. It is worth mentioning
that mononitration (with good yields) of all these systems under electrophilic conditions (HNO3
in CHCl3) was described earlier [12
Unexpectedly, we discovered lately that some free base porphyrins can react according to this scheme,
as well [14]. Finally, the -monosubstituted products, contrary to polysubstituted ones, are readily
,13]. Additionally zinc complex gave satisfactory results [2].
β
available by various other methods [15–20].
2.1. Nitration of Cobalt(II) and Copper(II) Complexes
Initially, in the reactions of cobalt complex 1b (under various conditions: 1–5% HNO3, 5 min, 2 h,
◦
0–20 C, in CHCl3, under argon) the formation of dinitro-compounds with yields in the 30–64% range
was observed. However, the products formed included partial decomplexation derivatives, yielding
practically inseparable mixtures. Thus, these experiments were temporarily suspended.
We found in our laboratory that copper complexes were the most convenient substrates for
these transformations (the total nitration yield is high and the chromatographic isolation of the
products is relatively satisfactory). Thus, the selected TPP copper(II) porphyrinate 1c was subjected

Molecules 2019, 24, 838
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to the reaction with nitric acid in CHCl3, applying the method based on our previously reported
procedures, elaborated for mononitration [12 13]. Initially, this electrophilic reaction with the
,
use HNO3 of higher concentration (35–55%, freshly prepared from fuming yellow nitric acid)
usually gave a mixture of dinitro-compounds, in 30–43% yield. These mixtures contained three
(or more)
β,β-dinitro-isomers: 2,7- (one spot on TLC) and 2,8-/3,7- (another spot on TLC) in a
ca 1:1 ratio. We found that from these mixtures the two major dinitro-isomers—2,7-dinitro- (3ca
)
and 3,7-dinitro-5,10,15,20-tetraphenyl-porphyrin-copper(II) (3cb)—could be isolated in considerable
amounts by precise column chromatography followed by preparative TLC (see Scheme 1 and
Experimental). In the remaining chromatographic fractions some amounts of these isomers were
still present. It should be also mentioned that in these reactions formation of the mononitro-product 2c
was observed, with variable yields (ca 10%).
In the case of this complex (1c), partial optimization of the reaction conditions allowed us to
obtain the best yield of β,β-dinitro-isomers when using 25% HNO3. Thus, treatment of 1c with
the above nitric acid in CHCl3 at room temperature (reaction time—30–40 min) gave moderate
amounts of monosubstituted product (2c, 28%) and a mixture of the desired dinitrated derivatives (56%
combined, confirmed by MS measurements) (Scheme 1). The above fractions were isolated by column
chromatography, however separation of the major dinitro-isomers required precise TLC conditions
(CHCl3/n-hexane—1:1). In this reaction five different dinitro-isomers may form (Scheme 1). The
investigations reported herein allowed us to identify the three main products.
Product 3ca (15%) and its isomer 3cb (13%) were obtained as analytically pure compounds.
Additionally, a fraction containing (2,8-dinitro-5,10,15,20-tetraphenylporphyrinato)copper(II) (3cc
;
contaminated with 3cb) was isolated (ca 10%). It could be further purified by preparative TLC.
The corresponding structures of the products 3ca–3cc couldn’t be assigned directly on the basis
of NMR due to the paramagnetic properties of the copper cation, thus some of them were identified
by comparison with authentic compounds obtained earlier in our laboratory as by-products of other
reactions, or selected compounds that were demetallated. Removal of the paramagnetic copper
cation allowed us to record 1H NMR spectra (see Supplementary Materials) and fully characterize
the products as the free base porphyrins 4a–c. This problem is discussed in details in Section 2.4. The
demetallation reactions were carried out in a mixture of acids (CF3CO2H/H2SO4) at room temperature
(15–30 min), leading to the metal-free derivatives in high yields (ca 90%, see Experimental).
2.2. Nitration of Nickel(II) Complex
In the case of nitration of the nickel complex 1d (20–30% HNO3, 10–40 min) we also
observed the formation of considerable amounts of a mixture of dinitro-derivatives (yield 18–64%),
always accompanied by mono-substituted product. Partial optimization of the reaction conditions
(a large excess of 30% HNO3/CHCl3, r.t., 30 min, under argon) allowed us to increase the
dinitration product yield of up to 73% (mononitro-derivative: 6.5%, known compound 2d [12]).
It is worth mentioning that the yield was calculated for two steps (complexation of TPP and
nitration) as the nickel complex 1d is only moderately soluble; its purification by column
chromatography is also somewhat trouble-some, thus decreasing the isolated yield. The crude
(meso-tetraphenylporphyrinato)nickel(II) (1d) when directly subjected to the nitration reaction gave
a mixture of several products from which only the 2-nitro-porphyrin 2d was isolated easily by
column chromatography, while a mixture of dinitro-compounds had to be separated additionally by
preparative TLC (CHCl3/n-hexane—2:1, developed four times). From this mixture of dinitro-moieties
two major isomers were isolated: (2,7-dinitro-meso-tetraphenylporphyrinato)nickel(II) (3da, 22%)
and (3,7-dinitro-meso-tetraphenylporphyrinato)-nickel(II) (3db, 22%). 1H NMR, MS, HR-MS and
UV-vis analyses confirmed their structures. In the 1H NMR of the 2,7-dinitro-compound 3da there are
two diagnostic downfield-shifted singlets of Hβ-protons neighbouring NO2 groups (8.89 ppm and
8.81 ppm) and two AB systems (in the region 8.56–8.69 ppm; from the remaining four
β-protons). This
is the only unsymmetrical -dinitro–substituted product. Thus, its identification was very simple,
β,β

Molecules 2019, 24, 838
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contrary to assignment of the spectrum of compound 3db. The latter case was not a trivial problem,
and is discussed below (Section 2.4).
2.3. Nitration of 5,10,15,20-tetrakis(3-Methylphenyl)porphyrin–Copper(II) Complex (5)
The above substitution orientation and the yields concerning
should also be observed for other porphyrin derivatives. Indeed, this was the case. We selected
[5,10,15,20-tetrakis(3-methylphenyl)porphyrinato]copper(II) ( ) for this experiment and its treatment
β,β-dinitration of TPP complexes
5
with the above nitric acid in CHCl3 gave similar results. Interestingly, all the possible dinitro-isomers
6a–10a were successfully isolated (see Figure 1).
NO2
NO2
NO2
Ar
M
Ar
M
Ar
M
NO2
Ar
M
Ar
M
NO2
Ar
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
Ar
Ar
Ar
Ar
Ar
Ar
Ar
Ar
Ar
NO2
NO2
O2N
Ar
Ar
Ar
NO2
Ar
O2N
Ar
6a, 22%
7a, 12%
8a, 5%
9a, 8%
10a, 7%
6b
7b
8b
9b
10b
Ar = 3-methylphenyl;
a: M = Cu, b: M = 2H
Figure 1. Structures of dinitro-isomers 6a–10a and 6b–10b.
1
2.4. H NMR Spectra and Structure Elucidation of the Isomers
The correct assignment of the corresponding structures to the obtained products was not trivial.
It was mainly accomplished on the basis of 1H NMR, however as the copper complexes used herein
are paramagnetic their spectra are not recordable. On the other hand, Cu-chelates were the most
convenient models for the studies (separation of the products was relatively satisfactory, yields were
good, and three isomers were isolated). Thus, we solved this problem indirectly. From the mixture
of dinitrated porphyrins three of them were isolated as pure individual compounds by preparative
TLC. Their demetallation using H2SO4/CF3CO2H gave copper-free isomers, which were examined
spectroscopically in details.
In the case of nickel products the isomers were analyzed as chelates. The identification of 3da
(2,7-dinitro-) was simple (see above) contrary to the assignment of the structure of the next isomer.
In the spectrum of the latter we found a singlet
an AB-like system (4H) at 8.63 ppm and 8.66 ppm (with J = 5.2 Hz). Unfortunately, these data are
in agreement with the three structures (3db 3dc 3dd; Figure 2). Structure 3de was not taken under
consideration because as a highly symmetrical one it should give in this region only three singlets
(3 2H). On the basis of two-dimensional COSY and NOESY measurements structure of 3db was
δ = 8.88 ppm originating from two β-protons, and
,
,
×
assigned. There is a diagnostic correlation between the signals at 8.06–8.02 ppm (2H) and the triplet at
7.58 ppm (J = 7.6 Hz, 2H) (see Figures 3 and 4). These signals are outside the two multi-H multiplets;
thus, the corresponding protons must be under the strong influence of NO2 groups. We therefore
ascribed them to the ortho- and meta-protons of one phenyl ring situated between two nitro groups.
This is in agreement with the proposed 3,7-dinitro-structure 3db. Moreover, in this analysis step the
isomer 3dd can be definitively excluded from the list of potential products because the integration
ratio of all the ortho-protons of the meso-phenyl rings should be equal to 4:4 in this case.

Molecules 2019, 24, 838
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NO2
NO2
Ph
Ni
NO2
Ph
Ph
Ni
Ph
Ni
NO2
Ph
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
Ni
Ph
Ph
Ph
Ph
Ph
Ph
Ph
N
NO2
O2N
O2N
Ph
Ph
Ph NO2
Ph
3db
3dc
3dd
3de
Figure 2. Structures of 3db, 3dc, 3dd, and 3de.
1
Figure 3. H NMR spectrum of product 3db (diagnostic region: 7.50–9.00 ppm).
H
H
ca 8.00
ca 8.00
H
H
H
8.66
H
8.06-8.02
8.88
8.63
ca 7.98
7.58
7.58
NO
H
H
H
2 H
H
H
N
N
N
N
Ni
H
H
H
NO2
H
ca 7.98
8.63
H8.88
8.06-8.02
8.66
H
H
H
ca 8.00
ca 8.00
H
H
Figure 4. The diagnostic 2D correlations observed for product 3db: COSY correlations—orange arches;
NOESY correlations—black arches.
Theoretically, the 2,8-dinitro-isomer 3dc could also give such a correlation pattern. Thus, the
structure 3db was definitively confirmed by the NOESY technique. In the spectrum several correlations
between protons due to their spatial proximity (Figure 4; black arches) were observed. The most
diagnostic one is the correlation of the ortho-phenyl protons,
the AB-like system (’the red protons’, at 8.66 ppm) from one side, and the two
the NO2 groups (’the green protons’, singlet at = 8.88 ppm), from the other side. Additionally, the
-protons of the remaining part of the AB-like system (2H, 8.63 ppm, ’the violet protons’) correlate
δ
= ca 8.00 ppm, with the two protons of
β
-protons neighbouring
δ
β

Molecules 2019, 24, 838
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with the ortho-protons of the last phenyl ring (
δ
= ca 7.98 ppm; in the 8.06–7.96 ppm multiplet). Finally,
no correlation between the ortho-protons at 8.06–8.02 ppm with any β-protons was observed. This
is an additional unambiguous evidence for the structure 3db. Moreover, demetallation of 3db and
comparison of the 1H NMR spectrum of the free base porphyrin obtained with the data observed
for 4b (in the light of the information given below), allowed us to find the same 3,7-disubstitution
pattern (the products were the same). By this way, we proved that the analyzed product, obtained in
the nitration of TPP(Ni) (1d), has structure 3db.
A similar analysis using 2D NMR techniques for a copper-free porphyrin 4b, obtained from 3cb
was performed earlier by Wyre˛bek [21]. After two-step transformation he isolated this product in 6%
yield and its spectroscopic data were in good agreement with that described herein (see Experimental).
In the case of the isomer 3ca (obtained in our experiments), the identification based on the 1H NMR
analysis of the demetallated porphyrin 4a was similar to 3da. In this series of compounds, again it was
the only unsymmetrical β,β-dinitro–substituted product.
,
We also isolated the partially contaminated 2,8-dinitro-5,10,15,20-tetraphenylporphyrin-copper(II)
(
3cc). In 1H NMR spectrum of its free base form 4c a very similar signal pattern was found. The key
difference is the appearance of a signal for the four β-protons (H-12, H-13, H-17, H-18) as a singlet.
Thus, also the structure of 3cc was indirectly proved (via demetallation).
3. Experimental
3.1. Materials and Methods—General.
1H NMR spectra were recorded with a GEMINI-200 or MR-400 spectrometers (both by Varian, Palo
Alto, CA, USA) operating at 200 MHz and 400 MHz, respectively. Coupling constants J are expressed
in Hertz [Hz]. Mass spectra were measured with a GCT Premier FD-TOF instrument (Waters, Milford,
MA, USA) (FD method), a MARINER ESI-TOF spectrometer (ESI method, PerSeptive Biosystems,
Framingham, MA, USA), and Synapt G2-S HDMS ESI-TOF spectrometer (ESI method) (Waters); m/z
intensity values for peaks are given as % of relative intensity. UV-vis spectra were measured with a
DU-68 (Beckman, Brea, CA, USA), SP-8001 (Metertech, Nangang, Taipei, Taiwan), UV-3600 (Shimadzu,
Chiyoda-ku, Tokyo, Japan), and V-730 (Jasco, Hachioji, Tokyo, Japan) spectrophotometers. TLC analysis
was performed on aluminium foil plates pre-coated with silica gel (60 F-254, Merck AG, Darmstadt,
Germany). All the products were isolated by column chromatography (silica gel, 230–400 mesh;
Merck AG). Some dinitro-isomers were additionally rechromatographed using preparative TLC plates
(silica gel, 60 F-254, 2 mm and 0.5 mm; Merck AG). Molecular formulas of new compounds were
confirmed by HR-MS (ESI, EI, and FD). Starting porphyrinates were obtained according to known
procedures described in the previous literature [12,13]. Some dinitro-derivatives were also reported.
Their 1H NMR, UV-vis, and MS spectra are in agreement with the spectra described herein. These
spectroscopic data are given below for more detailed and accurate characterization of the products.
3.2. Procedures and Data of New Compounds
3.2.1. Nitration of Copper(II) Complex of 5,10,15,20-Tetraphenylporphyrin (1c)
To a stirred solution of (meso-tetraphenylporphyrinato)copper(II) (1c; 237 mg, 0.35 mmol) in
CHCl3 (530 mL) at room temperature, a solution of 25% aqueous nitric acid (freshly prepared from
fuming yellow HNO3, d = 1.52; large excess, 140 mL, 637 mmol) was added dropwise during ca
5 min. The reaction mixture was intensively stirred under argon in a round-bottomed flask, protected
against light, for 30–40 min with TLC monitoring (CHCl3/n-hexane—1:1). Then, the mixture was
poured into aqueous solution of 5% NaHCO3 (200 mL), and shaken carefully in a separatory funnel.
The separated organic layer was washed with water (4
MgSO4/Na2CO3. After evaporating the solvent, the residue was subjected to column chromatography
×
200 mL), and dried with anhydrous
(eluent: CHCl3/n-hexane—1:1) to give (2-nitro-5,10,15,20-tetraphenylporphyrinato)copper(II)

Molecules 2019, 24, 838
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(2c
;
71 mg, 28%) and a mixture of dinitro-substituted isomers (150 mg, 56%).
The
dinitro-isomers were separated on preparative TLC (CHCl3/n-hexane—1:1, four times developed),
allowing isolation of: (a) (2,7-dinitro-5,10,15,20-tetraphenylporphyrinato)copper(II) (3ca; 40 mg,
15%); (b) (3,7-dinitro-5,10,15,20-tetraphenylporphyrinato)copper(II) (3cb; 35.5 mg, 13%); (c)
(2,8-dinitro-5,10,15,20-tetra-phenylporphyrinato)copper(II) (3cc) contaminated with small amounts
of (3,7-dinitro-5,10,15,20-tetraphenylporphyrinato)copper(II) (3cb) (30 mg, yield—ca 10%). 3cc can be
further purified by preparative TLC.
◦
It was reported earlier that when 50% HNO3 was used (temp. 5–10 C, reaction time—6 min,
the post-reaction mixture was poured into water with ice, followed by column chromatography:
CHCl3/n-hexane—from 1:1 to 2:1), two major isomers were isolated: 2,7-dinitro- (3ca) and
3,7-dinitro-5,10,15,20-tetraphenylporphyrin-copper(II) (3cb) [21]. However, the combined yield was
consider-ably lower (20%). Additionally, a mixture of the remaining dinitro-isomers was isolated (23%).
Products Data
(2-Nitro-5,10,15,20-tetraphenylporphyrinato)copper(II) (2c): known compound [12,15–17].
◦
(2,7-Dinitro-5,10,15,20-tetraphenylporphyrinato)copper(II) (3ca): m.p. > 300 C. UV-vis (CHCl3);
λ
max
[nm] (log ε): 559 (3.58), 438 (4.55, Soret band). MS (ESI); m/z (% rel. int.): 769 (14), 768 (42), 767 (78), 766
(81), 765 (100) [isotope M+• and (M + H)+]. HR-MS (ESI): m/z calcd for C44H26N6O4Cu [M+]: 765.1312;
found: 765.1327. MS (FD), m/z (% rel. int.): 769 (8), 768 (24), 767 (58), 766 (49), 765 (100) [isotope M+•].
HR-MS (FD): m/z calcd for C44H26N6O4Cu [M+]: 765.1312; found: 765.1344.
◦
(3,7-Dinitro-5,10,15,20-tetraphenylporphyrinato)copper(II) (3cb): m.p. > 300 C. UV-vis (CHCl3);
λ
max [nm] (log ε): 607 (4.02), 560.5 (4.19), 437.5 (5.25, Soret band), 388 (4.52), 326 (4.44). MS (FD), m/z
(% rel. int.): 769 (7), 768 (24), 767 (58), 766 (49), 765 (100) [isotope M+•]. HR-MS (FD): m/z calcd for
C44H26N6O4Cu [M+]: 765.1312; found: 765.1327.
◦
(2,8-Dinitro-5,10,15,20-tetraphenylporphyrinato)copper(II) (3cc): m.p. > 300 C. UV-vis (CHCl3);
λ
max
[nm] (log ε): 601.5 (4.21), 561 (4.43), 436.5 (5.45, Soret band). MS (ESI); m/z (% rel. int.): 769 (17), 768 (38),
767 (61), 766 (79), 765 (100) [isotope M+• and (M + H)+]. HR-MS (ESI): m/z calcd for C44H26N6O4Cu
[M+]: 765.1312; found: 765.1260.
The above products were also fully characterized as their corresponding decomplexed forms 4a
–c
(see below).
3.2.2. Nitration of Nickel(II) Complex of 5,10,15,20-Tetraphenylporphyrin (1d)
The substrate, (meso-tetraphenylporphyrinato)nickel(II) (1d), was prepared from 0.11 mmol
of TPP according to procedure described earlier for a similar compound [13], and it was directly
subjected to nitration reaction. This crude complex was dissolved in CHCl3 (200 mL) and to
a stirred solution obtained at room temperature, a solution of 30% aqueous nitric acid (freshly
prepared from yellow HNO3, d = 1.52; 13.8 mL, 77.5 mmol) was added dropwise via syringe
(using septum inlet) during ca 5 min. The reaction was carried out with intensive stirring in a
round-bottomed flask, protected against light, under argon, for 30 min. Then, the mixture was
poured into 5% aqueous solution of NaHCO3 (150 mL), and shaken carefully in a separatory funnel.
The separated organic layer was washed with water (4
MgSO4/Na2CO3. After evaporating the solvent, the residue was subjected to column chromatography
×
150 mL) and dried with anhydrous
(eluent: CHCl3/n-hexane—2:1) to give (2-nitro-5,10,15,20-tetraphenylporphyrinato)nickel(II) (2d
5.0 mg, 6.5%) and a mixture of dinitro–substituted compounds (61 mg, 73%). The dinitro-isomers
were separated by preparative TLC (CHCl3/n-hexane—2:1, developed four times), thus allowing
isolation of: (a) (3,7-dinitro-5,10,15,20-tetraphenylporphyrinato)nickel(II) (3db; 18.4 mg, 22%); (b)
(2,7-dinitro-5,10,15,20-tetraphenylporphyrinato)nickel(II) (3da; 18.4 mg, 22%); (c) an inseparable
mixture of the remaining dinitro-isomers (22 mg, 26%). All the above yields are calculated for
two steps.
;

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Products Data
(2-Nitro-5,10,15,20-tetraphenylporphyrinato)nickel(II) (2d): known compound; it has been already
described in our previous paper [12].
(2,7-Dinitro-5,10,15,20-tetraphenylporphyrinato)nickel(II) (3da): m.p. > 300 ◦C. 1H NMR (CDCl3,
400 MHz);
δ
[ppm]: 8.89 (s, 1H, Hβ-pyrrole), 8.81 (s, 1H, Hβ-pyrrole), 8.69 and 8.58 (AB system,
J = 5.1 Hz, 2H, Hβ-pyrrole), 8.64 and 8.56 (AB system, J = 5.1 Hz, 2H, Hβ-pyrrole), 8.02–7.95 (m, 8H,
H-Ph), 7.76–7.62 (m, 12H, H-Ph). UV-vis (CHCl3); λmax [nm]: 556.5, 449 (Soret band), 389.5, 329. MS
(FD), m/z (% rel. int.): 765 (4), 764 (12), 763 (23), 762 (50), 761 (51), 760 (100) [isotope M+•]. The above
data were in agreement with those described earlier [12].
(3,7-Dinitro-5,10,15,20-tetraphenylporphyrinato)nickel(II) (3db): m.p. > 300 ◦C. 1H NMR (CDCl3,
400 MHz);
8.06–7.96 (m, 8H, H-Ph), 7.78–7.68 (m, 10H, H-Ph), 7.58 (t, J = 7.6 Hz, 2H, H-Ph). UV-vis (CHCl3);
δ
[ppm]: 8.88 (s, 2H, Hβ-pyrrole), 8.66 and 8.63 (AB-like system, J = 5.2 Hz, 4H, Hβ-pyrrole),
λ
max
[nm]: 596, 553, 446 (Soret band), 382, 319. MS (FD), m/z (% rel. int.): 765 (4), 764 (12), 763 (22), 762 (50),
761 (53), 760 (100) [isotope M+•]. HR-MS (ESI): m/z calcd for C44H26N6O4Ni [M+]: 760.1369; found:
760.1403.
3.2.3. Demetallation
Demetallation reactions to give free base porphyrins were carried out according to modified
known procedures [12,13,22]: a) Cu-complexes (CF3CO2H/H2SO4, 1:1; r.t.; 15–30 min); yields: 4a from
3ca, 83%; 4b from 3cb, 93%; 4c from 3cc, 61%; b) Ni-complex (under conditions as above); yield of 4b
from 3db, 80%. The analytically pure products were fully characterized and the spectra confirmed the
structures. The compounds obtained from 3cb and from 3db exhibited identical spectral properties as
assigned to compound 4b.
Products Data
2,7-Dinitro-5,10,15,20-tetraphenylporphyrin (4a): m.p. > 300 ◦C. 1H NMR (CDCl3, 200 MHz);
δ [ppm]:
9.04 (s, 1H, Hβ-pyrrole), 9.03 (s, 1H, Hβ-pyrrole), 8.84 and 8.75 (AB system, J = 5.0 Hz, 2H, Hβ-pyrrole),
8.79 and 8.75 (AB system, J = 5.0 Hz, 2H, Hβ-pyrrole), 8.28–8.15 (m, 8H, H-Ph), 7.84–7.68 (m, 12H,
H-Ph),
−
2.17 (s, 2H, 2
×
NH). UV-vis (CHCl3);
λ
[nm] (log ε): 685 (3.42), 538.5 (3.55), 438 (4.68,
max
Soret band). MS (FD), m/z (% rel. int.): 707 (3), 706 (11), 705 (49), 704 (100) [isotope M+•]. HR-MS (EI):
m/z calcd for C44H28N6O4 [M+]: 704.2172; found: 704.2182.
3,7-Dinitro-5,10,15,20-tetraphenylporphyrin (4b): m.p. > 300 ◦C. 1H NMR (CDCl3, 400 MHz);
8.97 (s, 2H, Hβ-pyrrole), 8.79 and 8.76 (AB-like system, J = 5.0 Hz, 4H, Hβ-pyrrole), 8.29–8.26 (m, 2H,
H-Ph), 8.22–8.15 (m, 6H, H-Ph), 7.86–7.75 (m, 10H, H-Ph), 7.67 (t, J = 7.6 Hz, 2H, H-Ph), 2.25 (s, 2H,
δ [ppm]:
−
2
×
NH). UV-vis (CHCl3); λmax [nm] (log ε): 685 (3.76), 584 (3.92), 540 (3.90), 444.5 (5.09, Soret band).
MS (FD), m/z (% rel. int.): 707 (4), 706 (14), 705 (52), 704 (100) [isotope M+•]. HR-MS (EI): m/z calcd for
C44H28N6O4 [M+]: 704.2172; found: 704.2149.
2,8-Dinitro-5,10,15,20-tetraphenylporphyrin (4c): m.p. > 300 ◦C. 1H NMR (CDCl3, 200 MHz);
9.01 (s, 2H, Hβ-pyrrole), 8.93 (s, 4H, Hβ-pyrrole), 8.32–8.15 (m, 8H, H-Ph), 7.87–7.69 (m, 12H, H-Ph),
δ [ppm]:
−
2.49 and
−
2.58 (2
×
broad s, 2H, 2
×
NH). UV-vis (CHCl3); λmax [nm]: 682, 537.5, 434 (Soret band).
MS (ESI); m/z (% rel. int.): 707 (13), 706 (52), 705 (100), 704 (7) [isotope M+• and (M + H)+]. HR-MS
(ESI): m/z calcd for C44H29N6O4 [(M + H)+]: 705.2250; found: 705.2276.
In the previous paper [12] the structures for the 3,7- and 2,8-isomers 4b and 4c, obtained in small
amounts as by-products, were inversely assigned.

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3.2.4. Nitration of Copper(II) Complex of 5,10,15,20-tetrakis(3-Methylphenyl)porphyrin (5)
In a round-bottomed flask, to a stirred solution of complex 5 (102.4 mg, 0.140 mmol) in CHCl3
(130 mL), a solution of 33% aqueous nitric acid (freshly prepared from yellow HNO3, d = 1.52; 37.8 mL,
222 mmol) was added dropwise via syringe (using septum inlet) during ca 15 min, under argon, at
room temperature. The reaction was vigorously stirred for additional 10 min. Then, the mixture was
washed with water (4
×
70 mL), and the combined water layers were extracted with CHCl3 (25 mL).
The combined organic layers were dried over anhydrous MgSO4/Na2CO3. After evaporating the
solvent, the residue was subjected to column chromatography (CHCl3/n-hexane—1:1) to give:
(a) [2,7-dinitro-5,10,15,20-tetrakis(3-methylphenyl)porphyrinato]copper(II) (6a; 25.4 mg, 22%);
(b) [3,7-dinitro-5,10,15,20-tetrakis(3-methylphenyl)porphyrinato]copper(II) (7a; 13.8 mg, 12%);
(c) [2,8-dinitro-5,10,15,20-tetrakis(3-methylphenyl)porphyrinato]copper(II) (8a; 5.4 mg, 5%);
(d) [2,12-dinitro-5,10,15,20-tetrakis(3-methylphenyl)porphyrinato]copper(II) (9a; 8.9 mg, 8%);
(e) [2,13-dinitro-5,10,15,20-tetrakis(3-methylphenyl)porphyrinato]copper(II) (10a; 8.3 mg, 7%).
In some experiments traces of trinitro-isomers were detected (ca 1%, identified by MS). The
structures of the above compounds could not be elucidated due to the paramagnetic copper cation
inside the core ring, thus their 1H NMR spectra are not readable. Additionally, the compounds 8a
,
9a
were isolated as an inseparable mixture, so to determine the structures, all the compounds obtained
and the mixture 8a 9a were demetallated [12 13 22] to give free base porphyrins 6b 10b via column
chromatography (eluent: CHCl3/n-hexane). The spectral data of the products 6a 10a are given below.
Also the porphyrins 6b 10b were fully characterized. The yield of 8a and 9a was calculated on the
/
,
,
–
–
–
basis of the ratio of the separated 8b and 9b.
Products Data
◦
[2,7-Dinitro-5,10,15,20-tetrakis(3-methylphenyl)porphyrinato]copper(II) (6a): m.p. > 300 C. UV-vis (CHCl3);
λ
max [nm]: 606, 561.5, 440.5 (Soret band), 313. MS (ESI); m/z (% rel. int.): 847 (3), 846 (7), 845 (8), 844
(14) [isotope (M + Na)+], 825 (8), 824 (26), 823 (55), 822 (58), 821 (100) [isotope M+•]. HR-MS (ESI): m/z
calcd for C48H34N6O4Cu [M+]: 821.1938; found: 821.1925.
◦
[3,7-Dinitro-5,10,15,20-tetrakis(3-methylphenyl)porphyrinato]copper(II) (7a): m.p. > 300 C. UV-vis (CHCl3);
λ
max [nm] (log ε): 608.5 (3.53), 561.5 (3.67), 441.5 (4.80, Soret band), 271.5 (4.30). MS (ESI); m/z (% rel.
int.): 847 (7), 846 (14), 845 (14), 844 (25) [isotope (M + Na)+], 825 (9), 824 (29), 823 (61), 822 (63), 821
(100) [isotope M+•]. HR-MS (ESI): m/z calcd for C48H34N6O4Cu [M+]: 821.1938; found: 821.1924.
[2,8-Dinitro-5,10,15,20-tetrakis(3-methylphenyl)porphyrinato]copper(II) (8a) and [2,12-dinitro-5,10,
15,20-tetrakis(3-methylphenyl)porphyrinato]copper(II) (9a); inseparable mixture: MS (ESI); m/z (% rel.
int.): 847 (6), 846 (13), 845 (12), 844 (23) [isotope (M + Na)+], 825 (8), 824 (29), 823 (58), 822 (59), 821
(100) [isotope M+•].
◦
[2,13-Dinitro-5,10,15,20-tetrakis(3-methylphenyl)porphyrinato]copper(II) (10a): m.p. > 300 C. UV-vis
(CHCl3);
λ
[nm]: 606, 562.5, 435.5 (Soret band). MS (ESI); m/z (% rel. int.): 847 (6), 846 (12), 845 (12),
max
844 (23) [isotope (M + Na)+], 825 (8), 824 (29), 823 (58), 822 (59), 821 (100) [isotope M+•]. HR-MS (ESI):
m/z calcd for C48H34N6O4Cu [M+]: 821.1938; found: 821.1925.
◦
2,7-Dinitro-5,10,15,20-tetrakis(3-methylphenyl)porphyrin (6b): m.p. > 300 C. 1H NMR (CDCl3, 400 MHz);
[ppm]: 9.05 (s, 1H, Hβ-pyrrole), 9.03 (s, 1H, Hβ-pyrrole), 8.86 (d, J = 5.1 Hz, 1H, Hβ-pyrrole), 8.78
and 8.75 (AB system, J = 4.7 Hz, 2H, Hβ-pyrrole), 8.74 (d, J = 5.1 Hz, 1H, Hβ-pyrrole), 8.08–7.95 (m,
8H, H-Ar), 7.69–7.56 (m, 8H, H-Ar), 2.66 (s, 6H, 2 CH3), 2.64 and 2.63 (2 s, 6H, 2 CH3), 2.22
δ
×
×
×
−
(s, 2H, 2
×
NH). UV-vis (CHCl3); λmax [nm]: 683, 582, 540, 444 (Soret band), 366. MS (ESI); m/z (% rel.
int.): 764 (2), 763 (11), 762 (48), 761 (100) [isotope (M + H)+]. HR-MS (ESI): m/z calcd for C48H37N6O4
[(M + H)+]: 761.2876; found: 761.2855.

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◦
3,7-Dinitro-5,10,15,20-tetrakis(3-methylphenyl)porphyrin (7b): m.p. > 300 C. 1H NMR (CDCl3, 400 MHz);
[ppm]: 8.98 (s, 2H, Hβ-pyrrole), 8.79 and 8.76 (AB-like system, J = 4.9 Hz, 4H, Hβ-pyrrole), 8.11–7.95
(m, 8H, H-Ar), 7.69–7.52 (m, 8H, H-Ar), 2.67 (s, 6H, 2 CH3), 2.65 (s, 3H, CH3), 2.61 (s, 3H, CH3), 2.28
(s, 2H, 2 NH). UV-vis (CHCl3); max [nm] (log ): 684 (3.86), 587.5 (4.02), 539 (3.97), 446 (5.21, Soret
δ
×
−
×
λ
ε
band), 396.5 (4.49). MS (ESI); m/z (% rel. int.): 764 (2), 763 (11), 762 (45), 761 (100) [isotope (M + H)+].
HR-MS (ESI): m/z calcd for C48H37N6O4 [(M + H)+]: 761.2876; found: 761.2855.
◦
2,8-Dinitro-5,10,15,20-tetrakis(3-methylphenyl)porphyrin (8b): m.p. > 300 C. 1H NMR (CDCl3, 400 MHz);
[ppm]: 9.06 (s, 2H, Hβ-pyrrole), 8.85 (d, J = 4.7 Hz, 2H, Hβ-pyrrole), 8.73 (d, J = 4.7 Hz, 2H,
Hβ-pyrrole), 8.06–7.95 (m, 8H, H-Ar), 7.68–7.55 (m, 8H, H-Ar), 2.67 (s, 6H, 2
CH3), 2.62 (s, 6H,
CH3), NH—undetected. UV-vis (CHCl3); [nm] (log ): 679 (3.83), 580.5 (4.00), 538 (4.08),
δ
×
2
×
λ
max
ε
439.5 (5.26, Soret band), 363.5 (4.44), 328 (4.37). MS (ESI); m/z (% rel. int.): 764 (2), 763 (13), 762 (48),
761 (100) [isotope (M + H)+]. HR-MS (ESI): m/z calcd for C48H37N6O4 [(M + H)+]: 761.2876; found:
761.2860.
◦
2,12-Dinitro-5,10,15,20-tetrakis(3-methylphenyl)porphyrin (9b): m.p. > 300 C. 1H NMR (CDCl3, 400 MHz);
[ppm]: 9.02 and 8.92 (AA’XX’, JAX = 5.0 Hz, 4H, Hβ-pyrrole), 9.01 (s, 2H, Hβ-pyrrole), 8.11–7.98 (m,
8H, H-Ar), 7.70–7.57 (m, 8H, H-Ar), 2.68 (s, 6H, 2 CH3), 2.63 (s, 6H, 2 CH3), 2.61 (s, 2H, 2 NH).
UV-vis (CHCl3); max [nm] (log
δ
×
×
−
×
λ
ε): 685 (3.72), 538 (3.73), 436 (4.97, Soret band), 361.5 (4.01). MS (ESI);
m/z (% rel. int.): 764 (1), 763 (8), 762 (38), 761 (100), 760 (16) [isotope M+• and (M + H)+]. HR-MS (ESI):
m/z calcd for C48H37N6O4 [(M + H)+]: 761.2876; found: 761.2862.
1
2,13-Dinitro-5,10,15,20-tetrakis(3-methylphenyl)porphyrin (10b): m.p. > 300 ◦C. H NMR (CDCl3,
400 MHz);
8.12–7.97 (m, 8H, H-Ar), 7.69–7.57 (m, 8H, H-Ar), 2.67 (s, 6H, 2
1H, NH), 2.59 (s, 1H, NH). UV-vis (CHCl3);
δ
[ppm]: 9.02 (s, 2H, Hβ-pyrrole), 8.97 (s, 2H, Hβ-pyrrole), 8.92 (s, 2H, Hβ-pyrrole),
×
CH3), 2.64 (s, 6H, 2
[nm]: 688.5, 539.5, 441 (Soret band), 370, 276.5. MS
×
CH3),
−
2.50 (s,
−
λ
max
(ESI); m/z (% rel. int.): 785 (1), 784 (4), 783 (8) [isotope (M + Na)+], 764 (2), 763 (12), 762 (46), 761 (100),
760 (9) [isotope M+• and (M + H)+]. HR-MS (ESI): m/z calcd for C48H37N6O4 [(M + H)+]: 761.2876;
found: 761.2870.
4. Conclusions
We have described herein the preparation and isolation of dinitro-isomers of TPP complexes
(and their free base derivatives), which were formed in electrophilic nitration reactions of the parent
compounds. Some of these isomers were reported in previous papers, however they were formed
in low yields [6] (or as by-products [12]), and were not characterized in details or sometimes were
characterized erroneously (e.g., the 1H NMR spectra) [6,12].
In the above reactions the formation of five dinitro-isomers is possible. Usually, we could isolate
three of them (except for [5,10,15,20-tetrakis(3-methylphenyl)porphyrinato]copper(II)). In the case of
copper complexes, the products were treated with H2SO4/CF3CO2H mixture, thus giving metal-free
porphyrins that were also fully characterized. This type of porphyrins are practically not available by
alternative methods. The synthesis of potential anticancer PDT agents derived therefrom by our group
will be reported soon.
Supplementary Materials: The following are available online. Figures S1–S56 (1H NMR, UV-vis, and MS spectra
of all the products).
Author Contributions: Conceptualization, A.M. and S.O.; Methodology, A.M.; Formal Analysis, A.M. and M.R.;
Investigation, A.M. and M.R.; Writing—original draft preparation, A.M.; Writing—review and editing, S.O. and
A.M. In summary, A.M.—70%; M.R.—20%; S.O.—10%.
Funding: This research received no external funding.
Conflicts of Interest: The authors declare no conflict of interest.

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References
1.
Handbook of Porphyrin Science; Kadish, K.M.; Smith, K.M.; Guilard, R. (Eds.) World Scientific Publishing Co.:
New Jersey, NJ, USA; London, UK; Singapore; Beijing, China; Shanghai, China; Hong Kong; Taipei, Taiwan;
Chennai, India, 2010–2012; Volume 1–25.
2.
3.
Ostrowski, S. Preparation of 2-nitro-5,10,15,20-tetraphenylporphyrin zinc(II) complex—post scriptum to
electrophilic nitration of porphyrins at the β-pyrrolic position. Polish J. Chem. 2005, 79, 1169–1172.
Mikus, A.; Ostrowski, S. Synthesis of highly functionalized porphyrins—substituted in all β-positions
of EASTERN HALF. In Proceedings of the Petra International Conference of Chemistry (PICC) and
Transmediterranean Colloquium on Heterocyclic Chemistry (TRAMECH–5), Tafila, Jordan, 25–28 June
2007; p. 28.
4.
5.
6.
Ostrowski, S.; Wyre˛bek, P. The first example of Diels-Alder cycloaddition of ortho-xylylenes to
meso-tetraarylporphyrins containing electron-deficient
β,β-double bonds. Tetrahedron Lett. 2006, 47,
8437–8440. [CrossRef]
Fang, Y.; Jiang, X.; Ou, Z.; Michelin, C.; Desbois, N.; Gros, C.P.; Kadish, K.M. Redox properties
of nitro-phenylporphyrins and electrosynthesis of nitrophenyl-linked Zn porphyrin dimers or arrays.
J. Porphyrins Phthalocyanines 2014, 18, 832–841. [CrossRef]
Dahal, S.; Krishnan, V.; Nethaji, M. Isomers of β-substituted di and tri-nitrotetraphenylporphyrins and their
copper(II) derivatives: Structure, optical and electrochemical redox properties. Proc. Indian Acad. Sci. Chem.
Sci. 1998, 110, 37–52. [CrossRef]
7.
8.
Photodynamic Tumor Therapy: 2nd and 3rd Generation Photosensitizers; Moser, J.G. (Ed.) Harwood Academic
Publ.: Amsterdam, The Netherlands, 1998.
Vaz Serra, V.I.; Pires, S.M.G.; Alonso, C.M.A.; Neves, M.G.P.M.S.; Tomé, A.C.; Cavaleiro, J.A.S.
meso-Tetraarylporphyrins bearing nitro or amino groups: Synthetic strategies and reactivity profiles.
Top. Heterocycl. Chem. 2014, 33, 35–78.
9.
Taniguchi, M.; Lindsey, J.S. Synthetic chlorins, possible surrogates for chlorophylls, prepared by
derivatization of porphyrins. Chem. Rev. 2017, 117, 344–535. [CrossRef] [PubMed]
10. Wyre˛bek, P.; Osuch-Kwiatkowska, A.; Pakulski, Z.; Jarosz, S.; Ostrowski, S. Synthesis of sugar-decorated
hydrophilic porphyrins. J. Porphyrins Phthalocyanines 2013, 17, 384–391. [CrossRef]
11. Pandey, R.K. Recent advances in photodynamic therapy. J. Porphyrins Phthalocyanines 2000, 4, 368–373.
[CrossRef]
12. Ostrowski, S.; Szerszen´, D.; Ryszczuk, M. Electrophilic nitration of meso-tetraarylporphyrin complexes at the
β-pyrrolic position. Synthesis 2005, 37, 819–823. [CrossRef]
13. Wyre¸bek, P.; Ostrowski, S. Synthesis of some β-nitro-meso-tetraphenylporphyrin derivatives. J. Porphyrins
Phthalocyanines 2007, 11, 822–828. [CrossRef]
14. Mikus, A.; Zaja˛c, M.; Ostrowski, S. Frontiers in the electrophilic nitration of meso-tetraphenylporphyrin
derivatives. Org. Chem. Front. 2018, 5, 2840–2844. [CrossRef]
15. Giraudeau, A.; Callot, H.J.; Jordan, J.; Ezhar, I.; Gross, M. Substituent effects in the electroreduction of
porphyrins and metalloporphyrins. J. Am. Chem. Soc. 1979, 101, 3857–3862. [CrossRef]
16. Hombrecher, H.K.; Gherdan, V.M.; Ohm, S.; Cavaleiro, J.A.S.; Neves, M.G.P.M.S.; Condesso, M.F. Synthesis
and electrochemical investigation of β-alkyloxy substituted meso-tetraphenylporphyrins. Tetrahedron 1993,
49, 8569–8578. [CrossRef]
17. Alonso, C.A.A.; Neves, M.G.P.M.S.; Silva, A.M.S.; Cavaleiro, J.A.S.; Hombrecher, H.K. Reaction of
-amino-meso-tetraphenylporphyrin with -unsaturated carbonyl compounds: An approach to fused
β
α,β
pyridinoporphyrins. Tetrahedron Lett. 1997, 38, 2757–2758. [CrossRef]
18. Evans, B.; Smith, K.M.; Cavaleiro, J.A.S. Bile pigment studies. Part 4. Some novel reactions of
metallo-porphyrins with thallium(III) and cerium(IV) salts. Ring cleavage of meso-tetraphenylporphyrin.
J. Chem. Soc. Perkin Trans. 1 1978, 768–773. [CrossRef]
19. Catalano, M.M.; Crossley, M.J.; Harding, M.M.; King, L.G. Control of reactivity at the porphyrin
periphery by metal ion co-ordination: A general method for specific nitration at the β-pyrrolic position of
5,10,15,20-tetraaryl-porphyrins. J. Chem. Soc. Chem. Commun. 1984, 22, 1535–1536. [CrossRef]
20. Shea, K.M.; Jaquinod, L.; Smith, K.M. Dihydroporphyrin synthesis: New methodology. J. Org. Chem. 1998
63, 7013–7021. [CrossRef] [PubMed]
,

Molecules 2019, 24, 838
12 of 12
21. Wyre˛bek, P. Modification of porphyrin ring with the use of cycloaddition reactions. PhD Thesis, Uniwersytet
Przyrodniczo-Humanistyczny, Siedlce, Poland, 2011.
22. Smith, K.M.; Bisset, G.M.F.; Bushell, M.J. Partial syntheses of optically pure methyl bacteriopheophorbides c
and d from methyl pheophorbide a. J. Org. Chem. 1980, 45, 2218–2224. [CrossRef]
Sample Availability: Samples of the compounds are available from the authors.
©
2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access
article distributed under the terms and conditions of the Creative Commons Attribution
(CC BY) license (http://creativecommons.org/licenses/by/4.0/).