On selective functionalization of meso-tetraphenylporphyrin derivatives by Vicarious Nucleophilic Substitution of Hydrogen

Article abstract of DOI:10.3987/COM-02-9514

The studies on selective derivatization of meso-tetraphenylporphyrin (TPP) using nitration and Vicarious Nucleophilic Substitution of Hydrogen (VNS) are reported. TPP, its metal complexes and N,N-dimethyl substituted derivatives do not enter the VNS reaction. On the other hand, meso-substituted TPP results in the mono-nitration of one phenyl ring and the intermediate obtained, after simple transformation to its metal complex, reacts with carbanions bearing leaving groups at the carbanionic center, according to VNS scheme. This gives new opportunities for the peripheral functionalization of porphyrins. In this work the copper and zinc complexes were investigated.

Full text of DOI:10.3987/COM-02-9514

HETEROCYCLES, Vol. 57, No. 9, 2002, pp. 1615 - 1626, Received, 16th May, 2002
ON SELECTIVE FUNCTIONALIZATION OF meso-TETRA-
PHENYLPORPHYRIN DERIVATIVES BY VICARIOUS
NUCLEOPHILIC SUBSTITUTION OF HYDROGEN
Stanisław Ostrowski,*,a,c) Agnieszka Mikus,a) Young Key Shim,b)
Jong-Cheol Lee,b) Eun-Young Seo,b) Kee-In Lee,b) and Marian Olejnikc)
a) Institute of Chemistry, University of Podlasie, ul. 3 Maja 54, 08-110 Siedlce,
Poland; fax: (+48)-25-644-2045, e-mail: stan@ap.siedlce.pl
b) Bio-Organic Science Division, Korea Research Institute of Chemical
Technology, 100 Jang-Dong, Yuseong-Ku, Taejon 305-600, Korea
c) Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52,
01-224 Warszawa, Poland; fax: (+48)-22-632-6681, e-mail: stan@icho.edu.pl
Abstract - The studies on selective derivatization of meso-tetraphenylporphyrin
(TPP) using nitration and Vicarious Nucleophilic Substitution of Hydrogen (VNS)
are reported. TPP, its metal complexes and N,N-dimethyl substituted derivatives
do not enter the VNS reaction. On the other hand, meso-substituted TPP results in
the mono-nitration of one phenyl ring and the intermediate obtained, after simple
transformation to its metal complex, reacts with carbanions bearing leaving
groups at the carbanionic center, according to VNS scheme. This gives new
opportunities for the peripheral functionalization of porphyrins. In this work the
copper and zinc complexes were investigated.
Introduction
Some porphyrin derivatives are used as photosensitizers in Photodynamic Theraphy (PDT).1 PDT is a
treatment modality using photosensitising drugs and light to kill neoplastic cells.1b This simple technique
is currently evaluated in multiple clinical trials with promising results.2 The clinical use of PDT requires
the presence of a photosensitizing agent, oxygen, and light of a specific wavelenght, which matches the
absorption characteristic of the photosensitizer. Then, the photosensitizer is activated by an appropriate
wavelenght of light, and the energy is transferred through inter system crossing (ISC) to molecular
oxygen. This forms a toxic, short-lived species (singlet oxygen, 1O2), which is thought to mediate cellular
death.1b
Unsymmetrical, functionalized porphyrins have been also covalently incorporated into polymer
backbones3 and are known to serve as a useful synthetic precursors to monooxygenase and allosteric en-
zyme model systems.4,5 In oncology, the development of PDT has a potential to become an integral part

of cancer treatment in the future. This is relatively new technique, and is based on the administration of
tumor-localizing photosensitizers and their subsequent activation by visible light to destroy cancer cells.
However, their mode of action is still not clear. It has been known that human serum albumin (HSA)
binding affinity to various photosensitizers plays an important role in their biodistribution within the
tumor stroma,6 and the distribution of porphyrins among serum proteins is dependent upon their che-
mical structure.7
In light of this knowledge, the preparation of newer photosensitizers which would allow greater depth of
tissue penetration, is of particular interest. In spite of numerous studies in this field, new methods for
synthesis and derivatization of hydrophilic, lipophilic and amphiphilic porphyrins, especially unsym-
metrical ones, are continuously sought.
Results and Discussion
Herein, we present our studies on selective derivatization of porphyrins using Vicarious Nucleophilic
Substitution of Hydrogen (VNS).8 This reaction involves addition of a carbanion, bearing a leaving group
X at the carbanionic center, to a nitroarene (or other electrophilic aromatic or heteroaromatic compound)
followed by base induced β-elimination of HX, and protonation as a final step. This leads to the
substitution of hydrogen product (Scheme 1).
Scheme 1
X
-
B (-HX)
NO2
NO2
H
NO2
R
+
C
R
Y
X
R
Y
Y
+
H
NO2
R
Y
As model compounds to investigate the possibility of VNS in porphyrin systems easily available meso-
tetraphenylporphyrin (TPP, 1)9 and its derivatives (2-6) were selected (Figure 1). However, it is well
known that the VNS reaction proceeds smoothly and with high yield in electrophilic aromatic com-
pounds where free OH or NH-acidic groups are ”blocked” (e.g. with Me, CH2Ph, tetrahydropyranyl,
etc.10,11). Unsuccessful results of VNS attempts in 1 and 3 with carbanion of chloromethyl para-
tolylsulphone ClCH2SO2Tol (the standard nucleophile for this reaction) supports this hypothesis.
Afterwards, it was found that the meso-tetraphenylporphyrin (the compound without any additional
activating substituents, e.g. NO2) is not active enough to enter the above reaction. This was confirmed by
the use of the TPP derivative (4) in which the free NH-positions were protected with methyl groups.

Ph
M
Ph
Ph
N
N
N
N
NH
N
N
N
N
N
N
Ph
Ph
NO2
Ph
Ph
Ph
HN
Ph
Ph
Ph
1: M = 2H
2: M = Zn
3
4
Ph
Ph
outside aromatic ring
β2
β1
NO2
Nu
N
N
N
α
N
N
N
+
Ph
Ph
Ph
Ph
N
N
β3
β4
I
Ph
Ph
5
6
Figure 1
In this case, in the reaction of 4 with the carbanion of ClCH2SO2Tol we did not isolate any product.
1
However, we can postulate the formation of small amounts of the expected VNS compound as in H
NMR spectrum of the post-reaction mixture a diagnostic signal of AB spectral system at δ = 5.21 ppm
was observed (J ~ 10 Hz). This could be originating from the methylene group of CH2SO2Tol substituent
attached to pyrrole(s) in TPP (Figure 2).
AB, J = ca. 10 Hz
H
H
N
H3C
SO2
CH3
Figure 2
Next, the N,N-dimethyl derivative (4) was converted into the N,N,N-trialkyl porphyrinium salt (6).12 This
compound, being of higher electrophilicity than 4, should react with nucleophiles smoothly. In this case,
the possible addition of carbanion to porphyrin could take place at one of electronically equivalent activa-
ted positions: α, β1, β2, β3 or β4 (Figure 1). All β-positions bearing hydrogen could enter VNS. However,
β1 and β3 are outside the aromatic system and the carbanion did not react in these vinylic-like positions. It
could react in conjugated positions β2 and β4, which are in the aromatic framework; but they are far away
from the activating, positively charged, quarternary nitrogen atom. Additionally, they are also strongly
deactivated by N-alkyl fragments. Due to above reasons they are less active for nucleophilic addition than
position α-. No doubt, the addition is concidered to take place at position α- of pyrrole ring, destroying

[18π] electron system of porphyrin aromaticity, and due to lack of hydrogen in this position the VNS
reaction was not observed. Finally, the degradation (ring opening) of the macrocyclic moiety, under the
reaction conditions, occurred, and no defined products were isolated. Nevertheless, it is worth mentioning
that the N-alkyl substitution is not convenient protection for our purpose as the N-alkyl groups are not
labile ones and it is rather difficult to remove them, sometimes almost impossible.
Hence, in all investigated instances of the compounds (1, 2, 3, 4, and 6), the VNS reaction was not
occurred. We tried to check another model compound (of type 5) having protected NH-centers and NO2
electron-withdrawing activating group in phenyl ring or in β-position of pyrrole unit. Unfortunately, the
nitration of dimethyl compound (4) proved somewhat troublesome, and, due to selectivity problem, we
could not prepare the single defined nitro derivative from 4.
On the other hand, the nitration of meso-tetraphenylporphyrin (1) results in the mononitration in position
para- of one phenyl ring13 and in this case the transformation of the two NH-centers in the macrocyclic
ring into the metal complex, where the central metal cation is playing the role of a convenient protective
group for VNS reaction, allows the direct substitution of hydrogen. Thus, the intermediate (3), after
subsequent transformation to its copper complex, readily enters the VNS with good yield. This approach
was exemplified by preparation of a few porphyrin derivatives and it was described in the previous
communication.14 We found that the metallation15 offers very labile protection of NH functions and can
be easily removed after reaction, if needed.16
Scheme 2
Ph
Ph
-
X
N
N
N
N
1) B / solvent
2) H+
N
N
N
N
Ph
M
NO2
C
R
+
Ph
M
NO2
R
VNS
Y
Ph
Y
Ph
i)
7: M = Cu
8: M = Zn
3: M = 2H
9
10: M = Cu
11: M = Zn
(22 - 92%)
ii)
iii)
from10a
or 11i
12a or 12i (M = 2H)
9 - 12
a
b
c
d
e
f
g
h
i
j
X
Y
R
Cl
Cl
STol SO2Tol Cl
Cl
F
Cl
OC6H4Cl-p
Cl
SO2Tol SO2Tol
Me
CN
H
CN
H
SPh
H
SO2Ph SO2Ph SO2Ph SO2NMe
2 SO2Bu-t
H
Ph
H
H
H
H
i) Cu(OAc) xH2O, CHCl /MeOH, reflux, ca. 10 h, 92%;
2
3
ii) Zn(OAc) x2H2O, CHCl /MeOH, reflux, 4 h, quantitatively;
2
3
iii) CF3CO2H, H2SO4, rt, 3 h16

The use of Cu complex, due to paramagnetic
effect of the copper cation involved, caused
difficulty in following the reaction sequence
by NMR technique. However, we synthesized
and characterized (by MS and UV-VIS me-
thods) two compounds of this type (10a, 10c,
Table 1). In the case of 10a full characteriza-
tion could be finaly given for the demetallated
product (12a). Most of the examples
demonstrating the possibility of VNS reaction
were performed with the use of a zinc complex
- easy obtainable from the corresponding 5-(4-
nitrophenyl)-10,15,20-triphenylporphyrin (3)
with almost quantitative yield.
Table 1. Products and the yields.
Yield [b]
[%]
CH-acid
& Product
Entry
Method [a]
1
2
9a, 10a
9a, 11a
9a, 11a
9b, 11b
9c, 11c
9c, 11c
9d, 11c
9d, 11c
9c, 10c
9e, 11e
9e, 13
A
A
B
C
A
B
A
D
A
D
A
A
A
B
A
A
A
58[c]
88
3
71
4
13 (60)
66[c]
31 (86)
-
5
6
7
8
29 (57)
50[c]
-
9
10
11
12
13
14
15
16
17
Thus, nitro-porphyrin complexes (7,8) react in
the presence of t-BuOK with carbanions,
bearing leaving groups at the carbanionic
center (9-), in DMSO, DMF or in liquid am-
monia, giving in most cases, good yields of the
desired products. The substitution takes place
selectively in the phenyl ring in the ortho-
position to NO2. The use of heterogeneous
system, namely powdered NaOH in DMSO at
room temperature (Entry 3, Table 1), also gave
a satisfactory yield (71%). In the case of poor
leaving groups, such as X = OAr or F, the
conversion in the NaOH/DMSO system was
moderate or low (Entries 6,14). For the carb-
traces
-
9f,
-
9g, 11g
9h, 11g
9h, 11g
9i, 11i[d]
9j, 11j
79
< 5
22 (66)
92
76
[a]
see Experimental: A – t-BuOK / DMSO, rt;
B – NaOH / DMSO, rt; C – t-BuOK / DMF, -40°C;
D - t-BuOK/NH3 (liq.), [b] (in brackets) yields given
for consumed porphyrins, [c] see ref. 14, [d] the crude
product 11i was directly demetallated16 and charac-
terirized as 12i, the yield is given for 2 steps.
-
anion bearing poor leaving group X = SAr (9d ), a similar yield of the desired product was obtained
(this was only observed in the t-BuOK / liquid ammonia reaction system; Entry 8).
By this method we synthesized a series of new TPP derivatives, substituted with α-functionalized alkyl
groups, e.g. arylsulphonylmethyl- (10a, 11a,g), cyanomethyl- (10c, 11c), N,N-dimethyl-sulphonamide
(11i), etc. Some of the products give opportunities for further transformations and can be easily
converted into other derivatives, e.g. 11c to carboxylic acid and its esters.

Reactions with tertiary carbanions were unsuccessful due to steric hindrances. Bulky carbanions of low
nucleophilicity, e.g. generated from α-phenyl-(chloromethyl)phenylsulphone (9f), did not give any
product. Better results were obtained for α-chloroethyl para-tolylsulphone (9b), under the conditions
described earlier in the literature for unstable at higher temperature tertiary carbanions (t-BuOK/DMF,
-40°C17). However, in this case most of the starting material was recovered and the product (11b) was
isolated in 50% yield, calculated for consumed starting porphyrin (8).
In the reaction with phenylthiomethyl para-tolylsulphone (9e) we could not isolate any product. When
the crude post-reaction mixture was examined by Liquid Secondary Ions Mass Spectrometry
[LSIMS (+)], the molecular ion of the product of oxidative substitution of hydrogen (13) was identified
(m/z = 998; M+H, 2.5%). In this case the initial addition of the carbanion to porphyrin (8) occurred; but
SPh and SO2Tol are poor leaving groups18 and one could expect the difficulties in the elimination step.
Finally, the formation of small amounts of 13 was observed.
Ph
Ph
Ph
N
N
N
N
N
N
N
N
N
N
N
N
Ph
Zn
Ph
Ph
M
Ph
M
NO2
NO2
SO2Tol
SO2Tol
NO2
SPh
SO2Tol
NO2
NO2
a: M = 2H
b: M = Zn
a: M = Zn
b:
M = 2H
13
15
14
Figure 3
The VNS reaction in [5,10-bis(4-nitrophenyl)-15,20-diphenylporphyrinato]zinc(II) (14b) allows the
introduction of two α-functionalized substituents in two different phenyl rings. However, the zinc
complex (14b) and the compound (15a) are relatively unstable; hence, in the applied reaction conditions,
the product (15a) underwent partial decomposition to 15b. This was investigated by UV-VIS and MS
method.
Conclusions
The ability to access new types of porphyrin derivatives is of great importance due to biological activity
of these systems. In this paper we applied an useful nucleophilic methodology for their peripheral
functionalization. The VNS can be a new tool in this field for direct substitution of hydrogen in nitro-
substituted derivatives. It was also shown that the central metal cation in porphyrin complexes can play a
role as a labile and convenient protective group for the VNS process, and it can be easily removed after
reaction, if needed. Some of the compounds synthesized (10a; 11a,b,g,j; 12a) could have potential
bioactive properties (earlier, several sulphonyl TPP derivatives reavealed anti-cancer activity19).

EXPERIMENTAL
1H NMR spectra were recorded with a Varian GEMINI-200 and Varian 360 spectrometers operating at
200 MHz and 360 MHz, correspondingly. Coupling constants J are expressed in hertz. MS spectra were
measured with a Shimadzu GC MS-QD 5050A mass spectrometer using a direct insertion probe and an
AMD 604 (AMD Intectra GmbH, Germany) spectrometer (electron impact method); m/z intensity
values for peaks are given as a % of relative intensity. UV-VIS spectra were measured with Perkin
Elmer UV spectrophotometer Lambda 20. TLC analysis was performed on aluminium foil plates
precoated with silica gel (60F 254, Merck AG). Silica gel, 200-300 mesh (Merck AG), was used for
column chromatography.
Na,Nb-Dimethyl-meso-tetraphenylporphyrin (4) and Nc-ethyl-Na,Nb-dimethyl-meso-tetraphenylporphyrin
iodide (6) were prepared from TPP by the method described earlier in the literature.12 5-(4-Nitrophenyl)-
10,15,20-triphenylporphyrin (3) was obtained by nitration of TPP with HNO3 (d = 1.5, Aldrich)
according to the known procedure13 with 66% yield. 5,10-Bis(4-nitrophenyl)-15,20-diphenylporphyrin
(14a) was obtained as a by-product in the above nitration of TPP;13 4% yield.
[5-(4-Nitrophenyl)-10,15,20-triphenylporphyrinato]copper(II) (7): - 5-(4-Nitrophenyl)-10,15,20-tri-
phenylporphyrin (3; 24 mg, 0.036 mmol) and Cu(OAc)2 x H2O (100 mg, 0.5 mmol) in CHCl3 (10 mL)
and MeOH (1 mL) were refluxed for 2 h. After cooling, the reaction mixture was concentrated to
dryness and the residue was chromatographed (CHCl3 / n-hexane - 1:1) to give the desired product (24
mg, 92%). - mp >300°C. - UV-VIS (CH2Cl2), λmax (log ε): 578 (3.74), 539 (4.05), 485 (3.75), 415 (5.11,
Soret), 357 (3.83), 308 nm (3.97). - MS (EI), m/z (% rel. int.): 722 (41) and 720 (100) [isotopic M+.];
HR-MS calcd for C44H27N5O2Cu - 720.1461, found - 720.1460.
[5-(4-Nitrophenyl)-10,15,20-triphenylporphyrinato]zinc(II) (8): - 5-(4-Nitrophenyl)-10,15,20-triphe-
nylporphyrin (3; 320 mg, 0.485 mmol) and Zn(OAc)2 x 2H2O (888 mg, 4.0 mmol) in CHCl3 (90 mL)
and MeOH (10 mL) were refluxed for 4 h. After cooling the reaction mixture was concentrated to
dryness and the residue was chromatographed (at the beginning with CHCl3 / n-hexane - 1:1, then with
1
CHCl3) to give the desired product (350 mg, quantitatively). - mp >300°C. - H NMR (CDCl3, 200
MHz): 8.99 (d, J = 4.7 Hz, 2H, Hβ-pyrrole), 8.96 (s, 4H, Hβ-pyrrole), 8.84 (d, J = 4.7 Hz, 2H, Hβ-
pyrrole), 8.63 and 8.40 (AA’XX’, 4H, H-Ar(NO2)), 8.25-8.17 (m, 6H, H-Ph), 7.81-7.70 (m, 9H, H-Ph).
- UV-VIS (CH2Cl2), λmax (log ε): 589 (3.73), 548 (4.24), 513 (3.66), 419 (5.31, Soret), 348 nm (4.01).
- MS (EI), m/z (% rel. int.): 725 (28), 723 (40), 721 (56) [isotopic M+.], 675 (7), 661 (14), 660 (51), 659
(100), 613 (9), 598 (7), 361 (7), 330 (12), 300 (6), 298 (7); HR-MS calcd for C44H27N5O2Zn - 721.1456,
found - 721.1462.
[5,10-Bis(4-nitrophenyl)-15,20-diphenylporphyrinato]zinc(II) (14b): - This compound was obtained
from 5,10-bis(4-nitrophenyl)-15,20-diphenylporphyrin (14a; 14 mg, 0.020 mmol) and Zn(OAc)2 x

2H2O (56 mg, 0.25 mmol) according to the above procedure. After 4 h of reflux, additional 20 mg of
Zn(OAc)2 x 2H2O (0.09 mmol) was added and it was refluxed for the next 2 h. Chromatography with
CHCl3 gave 14b – 7 mg (46%); unstable. This was checking by UV-VIS (characteristic intensive band
of the complex; λmax = 550 nm) and MS, and it was used directly in the next step; - UV-VIS (CH2Cl2),
λmax (log ε): 590 (3.69), 550 (4.28), 5.14 (3.54), 418 (5.36, Soret), 350 (4.05), 291 nm (4.24). - MS (EI),
m/z (% rel. int.): 770 (12), 768 (17) and 766 (25) [isotopic M+.], 721 (6), 720 (6), 674 (5), 598 (6), 523
(5), 459 (13), 293 (10), 248 (8), 246 (10), 207 (20), 149 (39), 91 (49), 77 (62), 55 (62), 44 (100).
Vicarious Nucleophilic Substitution. General Procedures.
Procedure A. t-BuOK/DMSO: - To a stirred solution of t-BuOK (112 mg, 1.0 mmol) in andydrous
DMSO (3.5 mL, under argon) a solution of porphyrin derivative (7, 8 or 14b; 0.15 mmol) and a
carbanion precursor (9a, 9c-j; 0.30 mmol) in DMSO (1.5 mL) was added dropwise via syringe at room
temp. during ca. 10 min. After additional 20 min of stirring (50 min for 5c) the mixture was poured into
3% HCl with ice (50 mL). The precipitate was filtered, washed with water, and then dissolved in CHCl3.
After drying with anhydrous Na2SO4 and evaporation of the solvent the products were isolated by
column chromatography (eluent: CHCl3 or CHCl3/MeOH – 100:1); yields - see Table 1.
Procedure B. NaOH/DMSO: - To a stirred suspension of powdered NaOH (165 mg, 4.1 mmol) in
andydrous DMSO (5 mL, under argon) a solution of porphyrin derivative (8; 108 mg, 0.15 mmol) and a
carbanion precursor (9a, 9c, 9h; 0.30 mmol) in DMSO (1 mL) was added dropwise via syringe at room
temp. during ca. 1 min. After additional 1 h of stirring at room temp. the mixture was poured into 3%
HCl with ice (50 mL) and worked-up as in Procedure A (eluent for chromatography - CHCl3).
Procedure C. t-BuOK/DMF: - To a stirred solution of t-BuOK (56 mg, 0.5 mmol) in anhydrous DMF
(2 mL, under argon) a solution of porphyrin derivative (8; 54 mg, 0.075 mmol) and α-chloroethyl p-
tolyl sulphone (9b; 37 mg, 0.17 mmol) in DMF (1mL) was added dropwise via syringe at -40°C during
ca 10 min. After additional 50 min of stirring the mixture was poured into 3% HCl with ice (25 mL) and
worked-up as in Procedure A (eluent for chromatography: CHCl3 to CHCl3/MeOH – 100:1) to give 42
mg of the starting porphyrin (8; 77%) and 9 mg of the desired product (11b; 13%).
Procedure D. t-BuOK/NH3 (liq.): - To a stirred solution of t-BuOK (56 mg, 0.5 mmol) in liquid
ammonia (10 mL, under argon) a solution of porphyrin derivative (8; 54 mg, 0.075 mmol) and a carb-
anion precursor (9d or 9e; 0.20 mmol) in THF (1.5 mL) was added dropwise via syringe during ca. 5
min. The reaction was continued for additional 30 min, then it was completed by addition of NH4Cl (ca.
300 mg, in portions). The ammonia was evaporated and water (3 mL) and CHCl3 (10 mL) were added to
the residue. The organic layer was separated and the water phase was extracted with CHCl3 (2 x 3 mL).
The combined organic layers were dried over anhydrous Na2SO4. After evaporation of the solvent the
.

products were isolated by column chromatography (eluent: CHCl3) to give 28 mg (52%) of the starting
porphyrin (8) and 17 mg of the desired product (11c; 30%).
{5-[4-Nitro-3-(toluene-4-sulphonylmethyl)phenyl]-10,15,20-triphenylporphyrinato}copper(II) (10a):
- mp >300°C. The crude compound (10a) was analyzed by UV-VIS method (characteristic bands of
porphyrin complex; λmax: 576, 540, 490, 415 nm (Soret)), then it was demetallated and fully charac-
terized as a free base (12a).
{[2-Nitro-5-(10,15,20-triphenylporphyrinato-5-yl)phenyl]acetonitrile}copper(II) (10c): - mp >300°C.
- UV-VIS (CH2Cl2), λmax (log ε): 576 (3.96), 540 (4.27), 490 (3.97), 415 nm (5.30, Soret). - MS (EI),
m/z (% rel. int.): 762 (24) and 760 (52) [isotopic M + H], 761 (56) and 759 (100) [isotopic M+.], 742 (3),
718 (5), 713 (5), 712 (5), 636 (8), 635 (9), 559 (5), 380 (3); HR-MS calcd for C46H28N6O2Cu - 759.1570,
found - 759.1569.
{5-[4-Nitro-3-(toluene-4-sulphonylmethyl)phenyl]-10,15,20-triphenylporphyrinato}zinc(II) (11a):
1
- mp >300°C. - H NMR (CDCl3, 200 MHz): 9.02 (d, J = 4.8 Hz, 2H, Hβ-pyrrole), 8.98 (s, 4H, Hβ-
pyrrole), 8.83 (d, J = 4.8 Hz, 2H, Hβ-pyrrole), 8.37 (s, 1H, H-Ar(NO2)), 8.30-8.17 (m, 8H, 2H of H-
Ar(NO2) and 6H of H-Ph), 7.84-7.68 (m, 9H, H-Ph), 7.66 (apparent d, J = 8.5 Hz, 2H, H-Tol), 7.38
(apparent d, J = 8.5 Hz, 2H, H-Tol), 5.08 (s, 2H, CH2), 2.29 (s, 3H, CH3). - UV-VIS (CH2Cl2), λmax (log
ε): 590 (3.62), 549 (4.02), 420 (5.19, Soret), 348 nm (3.90). - MS (EI), m/z (% rel. int.): 893 (21), 891
(27), 889 (34) [isotopic M+.], 739 (3), 737 (5), 735 (9), 723 (6), 721 (10), 719 (15), 691 (9), 613 (5), 306
(4), 299 (4), 173 (14), 156 (14), 139 (10), 106 (15), 92 (52), 91 (100), 77 (10), 65 (27), 64 (53); HR-MS
calcd for C52H35N5O4SZn - 889.1701, found - 889.1699.
{5-{4-Nitro-3-[1-(toluene-4-sulphonyl)ethyl]phenyl}-10,15,20-triphenylporphyrinato}zinc(II) (11b):
1
- mp >300°C. - H NMR (CDCl3, 200 MHz): 9.10 (d, J = 4.9 Hz, 2H, Hβ-pyrrole), 9.00-8.96 (m, 4H,
Hβ-pyrrole), 8.81 (d, J = 4.9 Hz, 2H, Hβ-pyrrole), 8.70 (d , J = 1.4 Hz, 1H, H-Ar(NO2)), 8.32 (part of
AB coupled with another proton, J = 8.3,1.4 Hz, 1H, H-Ar(NO2)), 8.28-8.16 (m, 7H, 1H of H-Ar(NO2)
and 6H of H-Ph), 7.82-7.70 (m, 11H, 9H of H-Ph and 2H of H-Tol), 7.35 (apparent d, J = 8.4 Hz, 2H,
H-Tol), 5.83 (q, J = 7.2 Hz, 1H, CHCH3), 2.42 (s, 3H, CH3-Tol), 1.90 (d, J = 7.2 Hz, 3H, CHCH3).
- UV-VIS (CH2Cl2), λmax (log ε): 590 (3.89), 549 (4.18), 514 (3.87), 420 (5.27, Soret), 350 (4.02), 311
nm (4.10). - MS (EI), m/z (% rel. int.): 907 (10), 905 (13), 903 (17) [isotopic M+.], 736 (12), 734 (17),
721 (22), 719 (34), 717 (42), 689 (5), 675 (5), 598 (6), 359 (7), 156 (20), 139 (11), 124 (24), 91 (100),
64 (29), 59 (34); HR-MS calcd for C53H37N5O4SZn - 903.1858, found - 903.1861.
{[2-Nitro-5-(10,15,20-triphenylporphyrinato-5-yl)phenyl]acetonitrile}zinc(II) (11c): - mp >300°C.
- 1H NMR (CDCl3, 200 MHz): 9.03 (d, J = 4.7 Hz, 2H, Hβ-pyrrole), 8.99 (s, 4H, Hβ-pyrrole), 8.83 (d, J
= 4.7 Hz, 2H, Hβ-pyrrole), 8.60 (d, J = 8.8 Hz, 1H, H-Ar(NO2)), 8.58 (s, 1H, H-Ar(NO2)), 8.43 (dd , J =

8.8,1.4 Hz, 1H, H-Ar(NO2)), 8.29-8.21 (m, 6H, H-Ph), 7.83-7.74 (m, 9H, H-Ph), 4.50 (s, 2H, CH2CN).
- UV-VIS (CH2Cl2), λmax (log ε): 591 (3.77), 549 (4.23), 5.12 (3.72), 420 (5.41, Soret), 351 (4.03), 302
nm (4.14). - MS (EI), m/z (% rel. int.): 764 (42), 762 (70), 760 (100) [isotopic M+.], 719 (47), 636 (12),
380 (7), 299 (12), 149 (10), 91 (10); HR-MS calcd for C46H28N6O2Zn - 760.1565, found - 760.1566.
{5-[4-Nitro-3-(phenylsulphonylmethyl)phenyl]-10,15,20-triphenylporphyrinato}zinc(II) (11g): - mp
>300°C. - 1H NMR (CDCl3, 200 MHz): 9.11-8.80 (m, 8H, Hβ-pyrrole), 8.48-8.15 (m, 11H, H-Ar), 7.94-
7.47 (m, 12H, H-Ar), 5.22 (s, 2H, CH2). - UV-VIS (CHCl3), λmax (log ε): 597 (3.82), 555 (4.30), 424
(5.56, Soret), 313 nm (4.28). - MS (EI), m/z (% rel. int.): 879 (6), 878 (5), 877 (8), and 875 (12)
[isotopic M+.], 719 (2), 369 (5), 295 (8), 237 (21), 115 (17), 97 (51), 78 (36), 77 (33), 65 (12), 64 (39),
44 (100); HR-MS (ESI) calcd for C51H33N5O4SZn - 875.1545, found - 875.1543.
{5-[4-Nitro-3-(tert-butylsulphonylmethyl)phenyl]-10,15,20-triphenylporphyrinato}zinc(II) (11j):
- mp >300°C. - 1H NMR (CDCl3, 200 MHz): 9.04-8.94 (m, 8H, Hβ-pyrrole), 8.54 (d, J = 8.5 Hz, 1 H, H-
Ar(NO2)), 8.48 (d, J = 1.6 Hz, 1H, H-Ar(NO2)), 8.41 (dd, J = 8.5, 1.6 Hz, 1H, H-Ar(NO2)), 8.27-8.15
(m, 6H, H-Ph), 7.81-7.70 (m, 9H, H-Ph), 5.11 (s, 2H, CH2), 1.58 (s, 9H, C(CH3)3). - UV-VIS (CHCl3),
λmax (log ε): 598 (3.70), 554 (4.20), 423 nm (5.48, Soret). - MS (EI), m/z (% rel. int.): 859 (2), 857 (2),
and 855 (3) [isotopic M+.], 737 (2), 736 (2), 735 (4), 720 (1), 719 (1), 689 (1), 674 (1), 613 (1), 64 (94),
56 (43), 48 (35), 40 (100); HR-MS (ESI) calcd for C49H37N5O4SZn - 855.1858, found - 855.1852.
{5,10-Bis[4-nitro-3-(toluene-4-sulphonylmethyl)phenyl]-15,20-diphenylporphyrinato}zinc(II) (15a).
This compound was obtained according to Method A (contaminated with 15b). - 1H NMR (CDCl3, 200
MHz): 8.98-8.85 (m, 6H, Hβ-pyrrole), 8.79 (d, J = 5.0 Hz, 2H, Hβ-pyrrole), 8.58 (d, J = 8.2 Hz, 2H, H-
Ar(NO2)), 8.45-8.16 (m, 8H, 4H of H-Ar(NO2) and 4H of H-Ph), 7.84-7.68 (m, 10H, 6H of H-Ph and
4H of H-Tol), 7.33 (apparent d, J = 8.0 Hz, 4H, H-Tol), 5.21 (br s, 4H, 2xCH2), 2.34 (br s, 6H, 2xCH3).
- UV-VIS (CH2Cl2), λmax: 647, 590, 553, 517, 421 nm (Soret); log ε values are not given as the product
was partially demetallated. - MS (EI), m/z (% rel. int.): 1102 (<1, M+.), 947 (1, M-SO2Tol). LSIMS (+),
m/z (% rel. int.); the molecular ion of 15a was not detected, the ion of demetallated disubstituted
compound (15b) (C60H44N6O8S2) was identified: 1041 (1%, M+1).
Demetallation of the porphyrin complexes. – To a stirred solution of porphyrin complex (10a or 11i;
0.03 mmol) in CF3CO2H (5 mL) concentrated H2SO4 (1 drop) was added and the reaction mixture was
stirred at rt for 3 h. The reaction mixture was poured into water with ice (30 mL), the precipitate was
filtered, washed with water, and then dissolved in CH2Cl2. After drying with anhydrous Na2SO4 and
evaporation of the solvent, the products (12a, 12i) were isolated by column chromatography (eluent:
CHCl3 to CHCl3/MeOH – 100:1); quantitative yields.
5-[4-Nitro-3-(toluene-4-sulphonylmethyl)phenyl]-10,15,20-triphenylporphyrin (12a): - mp >300°C.

- 1H NMR (CDCl3, 200 MHz): 8.83 (d, J = 4.9 Hz, 2H, Hβ-pyrrole), 8.78 (s, 4H, Hβ-pyrrole), 8.66 (d, J
= 4.9 Hz, 2H, Hβ-pyrrole), 8.29 (part of AB, J = 8.3 Hz, 1H, H-Ar(NO2)), 8.25 (part of AB coupled with
another proton, J = 8.3,1.8 Hz, 1H, H-Ar(NO2)), 8.17 (d, J = 1.8 Hz, 1H, H-Ar(NO2)), 8.16-8.08 (m, 6H,
H-Ph), 7.72-7.64 (m, 11H, 9H of H-Ph and 2H of Tol), 7.21 (apparent d, J = 7.8 Hz, 2H, H-Tol), 5.12 (s,
2H, CH2), 2.20 (s, 3H, CH3), -2.88 (s, 2 H, 2xNH). - UV-VIS (CH2Cl2), λmax (log ε): 646 (3.93), 590
(3.98), 551 (4.05), 516 (4.25), 419 (5.37, Soret), 301 nm (4.18). - MS (EI), m/z (% rel. int.): 828 (31,
M+H), 827 (53, M+.), 687 (9), 673 (30), 657 (30), 644 (11), 629 (14), 156 (34), 139 (17), 92 (75), 91
(100), 65 (37), 64 (64); HR-MS calcd for C52H37N5O4S - 827.2566, found - 827.2561.
N,N-Dimethyl-C-{[2-nitro-5-(10,15,20-triphenylporphyrinato-5-yl)phenyl]methanesulphonamide}-
zinc(II) (12i): - mp >300°C. - 1H NMR (CDCl3, 200 MHz): 8.93 (d, J = 4.9 Hz, 2H, Hβ-pyrrole), 8.86 (s,
4H, Hβ-pyrrole), 8.83 (d, J = 4.9 Hz, 2H, Hβ-pyrrole), 8.51 (d, J = 1.4 Hz, 1H, H-Ar(NO2)), 8.46 (part of
AB, J = 8.4 Hz, 1H, H-Ar(NO2)), 8.38 (part of AB coupled with another proton, J = 8.4,1.4 Hz, 1H, H-
Ar(NO2)), 8.26-8.17 (m, 6H, H-Ph), 7.83-7.70 (m, 9H, H-Ph), 5.03 (s, 2H, CH2), 2.95 (s, 6H, N(CH3)2),
-2.80 (s, 2H, 2xNH). - UV-VIS (CHCl3), λmax (log ε): 653 (3.70), 591 (3.83), 553 (4.02), 516 (4.33), 420
nm (5.64, Soret). - MS (EI), m/z (% rel. int.): 782 (7), 781 (18), and 780 (34) [isotopic M+.], 721 (14),
676 (3), 675 (3), 656 (2), 655 (3), 628 (4), 627 (3), 626 (3), 369 (8), 295 (14), 281 (9), 221 (24), 121
(100), 91 (29), 78 (26), 57 (35), 55 (28), 44 (40), 40 (48); HR-MS calcd for C47H36N6O4S - 780.2519,
found - 780.2526.
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