Synthesis, biological evaluation, and docking studies of various β-substituted porphyrin conjugates embedded with N-containing heterocycles

Article abstract of DOI:10.1002/jhet.4314

A new methodology for the synthesis of some new β-porphyrin heterocyclic compounds containing nitrogen derivatives 10, 12, 13, 15, 17, 19, 21, 22, 25, 27, and 29 was screened for their cytotoxic activities. Both elemental and spectral analyses were used to confirm the structures of new compounds. Compounds 22, 27, and 21 exhibited very strong activity against the HepG2 cell line. Investigation of the binding between porphyrin 22 and the binding site of telomerase was performed by molecular docking.

Full text of DOI:10.1002/jhet.4314

Received: 5 April 2021
DOI: 10.1002/jhet.4314
Revised: 28 May 2021
Accepted: 30 May 2021
A R T I C L E
Synthesis, biological evaluation, and docking studies of
various β-substituted porphyrin conjugates embedded with
N-containing heterocycles
Ghada S. Masaret
Department of Chemistry, Faculty of
Abstract
Applied Science, Umm Al-Qura
University, Makkah Almukkarramah,
Saudi Arabia
A new methodology for the synthesis of some new β-porphyrin heterocyclic
compounds containing nitrogen derivatives 10, 12, 13, 15, 17, 19, 21, 22, 25, 27,
and 29 was screened for their cytotoxic activities. Both elemental and spectral
analyses were used to confirm the structures of new compounds. Compounds
Correspondence
Ghada S. Masaret, Department of
Chemistry, Faculty of Applied Science,
Umm Al-Qura University, Makkah
Almukkarramah, Saudi Arabia.
Email: ghadamasaret@yahoo.com
22, 27, and 21 exhibited very strong activity against the HepG2 cell line. Inves-
tigation of the binding between porphyrin 22 and the binding site of telome-
rase was performed by molecular docking.
1
| INTRODUCTION
synthesis of different heterocyclic derivatives [20–22].
From these above facts and in continuation to our inter-
Porphyrin derivatives are known as synthesizing drugs
and are widely used as anticancer agents, especially their
application for PDT “photodynamic therapy” [1] and
BNCT “boron neutron capture therapy” [2]. Such thera-
pies need activation of the tumor with light or low-energy
neutrons, respectively.
est in developing an attractive, and alternative synthesis
of mono(heteroaryl)tetraphenyl porphyrin through the
reaction of β-cyanoacetamide moiety in compound 8 with
bifunctional reagents and evaluation of their biological
activity as antitumor reagents.
Some porphyrin derivatives can selectively be local-
ized in tumor tissues, this may be due to their ability for 2 | RESULTS AND DISCUSSION
carrier biomolecules and/or biological members [3].
Some positively charged porphyrins showed strong inter- 2.1 | Chemistry
action with negatively charged functions of proteins,
DNA, and RNA to be active toward PDT [4–7].
Therefore, 3-nitropyrrole (5) was prepared by the follow-
ing reaction sequence in which starting with the reaction
of pyrrole (1) with sodium hydride in dimethylformamide
Moreover, aromatic nitro compounds are found to be
effective electron-affinity ratio sensitizers [8]. Also, com-
pounds having nitro and amino groups can be conjugated
with biologically active compounds [9–15].
ꢀ
(DMF) at 0 C to give N-sodium salt (2) [23]. Compound
2 was subjected to react with triisopropylsilyl chloride to
give 1-(triisopropylsilyl) pyrrole (3) [23]. When com-
pound 3 was reacted with cupric nitrate trihydrate in
acetic anhydride at room temperature for 1 h afforded
3-nitro-1-(triisopropylsilyl) pyrrole (4) [23]. Compound
4 was converted to 3-nitropyrrole (5) by reaction with
tetrabutylammonium fluoride in THF [23] (Scheme 1).
The main problem in porphyrin synthesis is its low
yields (6%–20%) although different trials to enhance the
yields of porphyrins are reported [24–26]. Recently,
Nitration of metallo porphyrinates by radical condi-
tions gave mononitrate the macrocycle at the β-position
by using a variety of oxidants [16,17]. Nitration by radical
condition [18] and catalyzed by sulfuric acid [19] of free-
base porphyrin are published to yield β and some meso
substitution products. No nitration of phenyl group was
observed in these studies.
Moreover, cyanoacetamide derivatives are considered
one of the most significant starting materials for the
J Heterocyclic Chem. 2021;1–13.
wileyonlinelibrary.com/journal/jhet
© 2021 Wiley Periodicals LLC.
1

2
MASARET
SCHEME 1 Synthesis of
-nitropyrrole from pyrrole
3
Fadda et al. [27,28] reported a new methodology, which
(5,10,15,20-tetraphenylporphyrin-2,7,12,17-tetrayl)tetrakis
(2-cyanoacetamide) (8) was achieved by heating com-
pound 7 with cyanoacetic acid in presence of drops of
acetic anhydride. The structure of 8 was elucidated by
spectroscopic data. The IR spectrum revealed the disap-
yields 70%–80% yield. In this case, Fadda et al. used DMF
“N,N-dimethylformamide” as a solvent and capping
reagent. The capping mechanism prevents the pyrrole
polymerization process. The intermediate DMF-pyrrole
reacts with another pyrrole moiety to give the
corresponding porphyrinogen. When each time pyrrole is
added, loss of DMF molecule was appropriate as a good
leaving group [27,28]. In this work, we report here the
synthesis of free-base porphyrin 6 in high yields (75%).
Therefore, it was found that 2,7,12,17-tetranitro-
pearance of the band due to NH groups, instead showed
2
ꢁ
1
bands at 3300, 3150, 2220, and 1685 cm corresponding
to NH, C≡N, and CO amidic functions, respectively. H
1
NMR showed a characteristic signal at δ 3.50 ppm due to
CH protons (Scheme 2).
2
1,8-Naphthyridine derivatives showed mild activity
toward murine p388 leukemia when changes were car-
ried out at N-1 and N-7 positions [38,39]. These above
facts and in continuation of previous work from our lab
in 1,8-naphthyridine derivative [40], we synthesized new
1,8-naphthyridine derivative 10 by Friedlander
cyclocondensation of 8 with nicotine aldehyde 9 in
5
,10,15,20-tetraphenylporphyrin (6) was synthesized from
the reaction of 3-nitropyrrole (5) with benzaldehyde
according to the reported method by Fadda et al. [27,28].
The synthesized porphyrin was well characterized by
1
spectral data. The H NMR spectra, porphyrin derivative
6
showed C -H, C -H, C -H, and C -H protons
2 8 13 18
1
appeared at δ 6.61, 7.54, 7.74, and 9.14 ppm, respectively.
The endocyclic NH showed two bands at δ 8.97 and 9.74,
respectively, besides aromatic protons appeared at δ 7.17–
refluxing ethanol containing piperidine as a catalyst. H
NMR of 10 displayed signals at δ 2.48, 2.88, 5.51, 5.77,
6.27, 6.51, 7.24–7.45, 8.11, 8.48, 8.88, 9.55, 9.65, and
11.00 ppm corresponding to naphthyridine two methyl
protons, C -H, C -H, (pyrrole protons), NH protons,
13
7
.74 ppm. Compound 6 displayed in its C NMR charac-
teristic signals at δ 119.2 for C-2, 152.1 for C-7 and C-17,
and carbon atom attached to nitro group appeared at δ
8
13
2
C -H pyrrole, aromatic protons, C -H naphthyridine pro-
3
5
1
42.4 ppm (Scheme 2).
ton, NH endocyclic, NH exocyclic, 2NH exocyclic, NH
endocyclic, and exocyclic NH proton, respectively
(Scheme 3).
Regarding the low solubility of the nitro porphyrin
(
6), it was reduced into the corresponding amino porphy-
rin (7) by tin(II) chloride and HCl in yield 60%, according
to the previously reported work [29,30]. C NMR of com-
pound 7 showed characteristic signals at δ 157.1 for C-2,
Many reported works showed that quinoline deriva-
tives had been evaluated for their antibacterial and
antifungal activities and were found active against Vib-
rio cholerae and Escherichia coli [41]. Therefore, these
facts prompted us to synthesize new porphyrin con-
taining quinoline moiety. So it has been found that
cyanoacrylamide derivative 11 was obtained by conden-
sation of 8 with o-nitrobenzaldehyde in refluxing etha-
nol with piperidine as a catalyst, which on reductive
cyclization of 11 with iron in boiling acetic acid
furnished quinoline 12. Structures of 11 and 12 were
established by spectral data. IR spectrum of 11
13
1
44.8 for C-7 and C-17, and at 129.2 for C-12, respec-
1
tively. H NMR of compound 7 displayed signals at δ 3.83
(
C -NH ), 4.79 (NH protons at C and -C ), and at δ
2 2 2 7 17
6
.79 for NH protons at C , respectively. Moreover, four
2 12
singlet signals at δ 6.35, 4.98, 5.18, and 6.58 appeared
attributable to protons at C , C , C , and C , respec-
3
8
13
18
tively (Scheme 2).
As a continuation of our interest in the chemistry
0
00
000
of cyanoacetamide [20–22,31–37], N,N ,N ,N -

MASARET
3
SCHEME 2 Synthesis of 3-
nitropyrrole from pyrrole
displayed stretching vibration bands at 3310, 3120,
the C -H quinoline ring. In a two-step reaction mechanism
4
ꢁ
1
2
220, 1685, 1620, 1600, 1530, and 1350 cm
using microwave irradiation, three-components condensa-
tion of dimedone, Dimethylformamide/Dimethylacetal
(DMF/DMA), and compound 8 gave the corresponding
corresponding NH, CN, CO, C=N, C=C, symmetric and
1
asymmetric NO function groups. The H NMR spectrum
2
1
showed a characteristic singlet signal at δ 8.85 due to ole-
finic protons. The IR spectrum of compound 12 showed
2-pyridone derivative 13. H NMR of compound 13 dis-
played, some selected singlet, signals at δ 1.11, 2.27,2.85,
7.27, 7.85, 10.75, and 12.58 corresponding to two methyl
protons of dimedone ring, CO-CH , CH , C -H, C -H
ꢁ
1
1
the NH absorption band at 3370–3300 cm . The H NMR
2
spectrum displayed a singlet signal at δ 8.31 ppm due to
2
2
17
4

4
MASARET
SCHEME 3 Synthesis of 3-nitropyrrole from pyrrole
pyridine ring, exocyclic NH, and NH pyridine ring, respec-
tively (Scheme 3).
Due to the importance of pyridine derivatives as anti-
fungal, antiviral, antioxidant, antidiabetic, anticancer,
antimalarial, anti-inflammatory, and antiamoebic agents
route for 2-pyridone derivative was achieved by reaction
of cyanoacetamide 8 with 2-arylmethyleneindan-1,-
3-dione (14) in refluxing benzene in the presence of
1
3
ammonium acetate afforded 2-pyridone derivative 15.
C
NMR of 15 showed signals at 115.8, 136.0, and 162.9 ppm
characteristic for CN, CO, and N-CO carbon atoms,
respectively (Scheme 3).
[
42–46], we decided to synthesize some new porphyrin
carrying pyridine moiety. So, a convenient and simple

MASARET
5
Compound 8 reacts with ketene dithioacetal 16 in
at δ 1.77, 2.27, 3.11, 5.95, and 10.85 ppm corresponding to
refluxing DMF catalyzed by anhydrous potassium car-
bonate gave pyridine-2-one derivative 17. H NMR of
C -CH , C -CH , C -H pyridine, C -H pyridine, and NH,
respectively (Scheme 4).
4
3
2
3
5
3
1
compound 17 displayed signals at δ 2.80 and 6.58 due to
Heating of 8 with malononitrile dimer in pressure
tube in silicon oil furnished pyridine derivative 22. The
same product was obtained when 8 was boiled with two
moles of malononitrile in refluxing ethanol containing a
catalytic amount of piperidine. Moreover, a reaction of
8 with ethyl-2-arylhydrazono-3-buterate (23) in boiling
benzene-acetic acid mixture yielded pyridazine 25. The
S-CH and NH protons (Scheme 3).
3
2
On the other hand, the reaction of 8 with ethyl
3
-cyano-2-methyl-but-2-enate 18 in presence of sodium
1
ethoxide furnished pyridine derivative 19. H NMR of
compound 19 showed a characteristic three singlet sig-
nals at δ 0.99 and 3.11 ppm due to two methyl protons
and two CH protons, respectively (Scheme 3). Reaction of
compound 8 with hydrogen sulfide afforded 3-amino-N-
1
reaction proceeded via the intermediate 24. H NMR of
25 displayed a characteristic triplet and quartet signals at
δ 1.25 and 4.11 due to ethyl protons of the ester group
(Scheme 4).
(
3
5-cyano-2-phenyl-6-[p-tolyl]pyrimidine-4-yl)-
-thioxopropanamide (20). H NMR of compound 20 dis-
1
played two singlet signals at δ 3.77 and 6.85 ppm referred
Reaction of cyanoacetamide 8 with 2-amino-3-car-
boxy-5-cyano-4,6-diphenyl-4H-pyran (26) in boiling pyri-
dine affords dihydropyrano-[2,3-d]-pyrimidinone (27).
Also, the reaction of 8 with DMF/DMA in refluxing dry
xylene gives enaminonitrile 28. Treatment of 28 with
5-phenyl-3-amino pyrazole in DMF and few drops of
13
to CH and NH protons, respectively. The C NMR
2
2
showed signals at 53.2 corresponding to CH2 carbon
atom. Treatment of 20 with acetylacetone in boiling etha-
nol in presence of triethylamine as catalyst affords
1
pyridine-2-thione derivative 21. H NMR referred signals
SCHEME 4 Synthesis of 3-
nitropyrrole from pyrrole

6
MASARET
piperidine furnished pyrazolo-[1,5-a]pyrimidine (29). IR
spectrum of 29 showed absorption band at 3360, 3100,
an IC50 value of 9.16 ± 1.5 μg/ml. Compound 21 showed
very high activity toward MCF-7 with an IC50 value of
9.91 ± 0.9 μg/ml. Compound 10 showed very high activ-
ity toward HCT-116 cell line, compounds 12 and 13 dis-
played high activity toward HePG-2 cell line with IC50
values 17.08 ± 1.6 and 16.73 ± 1.4 μg/ml, compound 20
exhibited high activity toward the three cell lines. Deriva-
tive 21 displayed very high activity toward the MCF-7 cell
line and high activity against the two other cell lines with
IC50 values 9.91 ± 0.9, 11.64 ± 1.2, and 16.44
ꢁ
1
1
675, and 1610 cm due to NH , NH, CO, and C=N
2
function groups (Scheme 4).
2.2 | Biological evaluation
2.2.1 | Evaluation of antitumor and
cytotoxicity
±
1.6 μg/ml, respectively. Compound 25 showed very
Anti-cancer activity in vitro against three cell lines,
strong activity against the HePG-2 cell line with an IC50
16.06 ± 1.5 μg/ml, while compound 29 displayed strong
activity against both HePG-2 and HCT-116. The other
rest of the compounds displayed moderate-weak activity
toward the tested cell lines.
“
1
hepatocellular carcinoma (HePG-2), colon cancer HCT-
16, and mammary gland breast cancer (MCF-7)” were
tested for all the new porphyrin derivatives. Growth
inhibitory concentration values (IC ) were used to reflect
50
the anticancer activity (Table 1). Compound 22 displayed
very strong activity toward all tested cell lines with an
IC50 value of 9.62 ± 0.9, 5.16 ± 1.4, and 5.05 ± 1.6 μg/ml.
Compound 27 showed the optimal result (high activ-
ity) with an IC50 value 10.13 ± 0.8, 7.49 ± 0.6, and 7.13
2.2.2 | Structure–activity relationship (SAR)
1. Compound 22 with IC50 (9.62 ± 0.9 and 5.05 ± 1.6)
against HePG2 and MCF-7, respectively, showed the
presence of four sets of disubstituted amino groups
meta to each other exposed out to the celling of the
DNA groove enhanced the hydrophilic recognition.
±
0.6 μg/ml for the three cell lines. Compound 10 dis-
played very high activity against HCT-116 cell line with
TABLE 1 Cytotoxicity (IC50) of the tested compounds on
2
3
4
. Compound 27 with IC50 (10.13 ± 0.8 and 7.13 ± 0.6)
against HePG2 and MCF-7, respectively, showed four
well-distributed pyrimidine-one fused rings that
showed considerable hydrophilic interaction with
the backbone. However, the diphenyl rings substitu-
tion on the pyrane fused ring performed high hydro-
phobic interactions with the out-pocket surface.
. Compound 21 with IC50 (11.64 ± 1.2 and 9.91 ± 0.9)
against HePG2 and MCF-7, respectively, showed the
presence of function 2-thiopyridine showed proper
electrostatic balance with the two methyl functions.
However, shrinking the linker by using amido func-
tion instead of acetamido spacer dwindles the overall
biological effect.
different cell lines
a
IC50 (μg/ml)
Compound no.
HePG2
HCT-116
MCF-7
6
7
8
64.13 ± 3.6
44.89 ± 3.1
31.12 ± 2.3
13.78 ± 1.1
23.85 ± 1.9
17.08 ± 1.6
16.73 ± 1.4
44.89 ± 3.1
47.34 ± 3.3
25.94 ± 2.2
13.78 ± 1.1
11.64 ± 1.2
9.62 ± 0.9
16.06 ± 1.5
10.13 ± 0.8
31.12 ± 2.3
14.88 ± 1.3
4.50 ± 0.2
70.46 ± 3.8
28.44 ± 1.6
21.87 ± 1.7
9.16 ± 1.5
50.92 ± 2.9
29.42 ± 2.3
28.46 ± 1.8
38.46 ± 2.3
33.42 ± 2.3
35.19 ± 2.4
19.55 ± 1.5
16.44 ± 1.6
5.16 ± 1.4
21.87 ± 1.7
7.49 ± 0.6
28.46 ± 1.8
11.24 ± 1.1
5.23 ± 0.3
67.16 ± 3.9
40.53 ± 2.8
39.5 ± 2.7
12.78 ± 1.2
43.88 ± 3.1
28.13 ± 2.2
28.07 ± 1.5
53.2 ± 3.6
41.53 ± 2.8
51.32 ± 3.5
12.98 ± 1.2
9.91 ± 0.9
5.05 ± 1.6
26.33 ± 2.0
7.13 ± 0.6
33.88 ± 3.1
28.13 ± 2.2
4.17 ± 0.2
1
1
1
1
1
1
1
2
2
2
2
2
2
2
0
1
2
3
5
7
9
0
1
2
5
7
8
9
. Compound 10 with IC50 (13.78 ± 1.1 and 12.78
±
1.2) against HePG2 and MCF-7, respectively, has
key functions including the dimethyl-substituted
pyrido-pyridine in addition to the free amino func-
tion that present neighbor to the amido linkage
augmenting the electrostatic filed showed a proper
biological effect.
5
6
. Compound 20 with IC50 (13.78 ± 1.1 and 12.98
±
1.2) against HePG2 and MCF-7, respectively, has a
significant donating open chain; thiocarbamoyl acet-
amide that enhances the biological effect.
. Compound 29 with IC50 (14.88 ± 1.3 and 28.13 ± 2.2)
against HePG2 and MCF-7, respectively, amido and
amino substitutions of the pyrazolopyrimidine
DOX
Abbreviation: DOX, doxorubicin.
a
IC50 (μg/ml): 1–10 (very strong); 11–20 (strong); 21–50 (moderate); 51–100
(
weak); above 100 (noncytotoxic).

MASARET
7
enhance the electron donor interaction with the sur-
rounding DNA base pairs. While the outer phenyl
function balances the lipophilic interaction.
7
8
. Compound 25 with IC50 (16.06 ± 1.5 and 26.33
±
2.0) against HePG2 and MCF-7, respectively, that
has both of ethyl carboxylate side chain of the
pyridazine ring and the imino-function are per-
forming proper donor–acceptor.
. Compound 7 with IC50 (44.89 ± 3.1 and 40.53 ± 2.8)
against HePG2 and MCF-7, respectively, which con-
tains amino group, in comparison with compound
6
that has nitro substitution, compound 7 showed a
more proper biological effect that may correlate with
the enriched amino electrostatic field.
. Compound 15 with IC50 (44.89 ± 3.1 and 53.2 ± 3.6)
against HePG2 and MCF-7, respectively, showed
rigidity of the indenopyridinone fused ring decline
the recognition and inturn drop the biological effect.
0. Compound 6 with IC50 (64.13 ± 3.6 and 67.16 ± 3.9)
against HePG2 and MCF-7, respectively, which con-
tains nitro electron-withdrawing group showed mini
electrostatic recognition within the DNA groove.
FIGURE 1 Putative docking interaction of ligand POH 25A
that was in complex of G-quartet DNA (PDB code 2A5R)
9
research considering the small molecules with potential
telomerase inhibition. In this study, we aimed to find effi-
cient G-quartets ligands that would be able at the same
time to discriminate between different forms of nucleic
acids to be selective as telomeric DNA.
Large porphyrin ligand 22 perfectly overlaps with G-
quartets and professionally capped the quadruplex
groove.
1
2.2.3 | Docking antitumor active
porphyrin 22
2.2.6 | Docking studies of compound 22
Molecular docking of compound 22 into the binding site of
telomerase was expressed using Discovery Studio 2020
Telomerase and compound 22 have strong complemen-
tarities as it sandwiched between the inside the major
groove of telomeric DNA as the reference ligand POH
25A in addition to the two of the phenyl groups and two
the substituted pyridines merged out to seal off the
groove entry (Figure 2).
[47]. The three-dimensional structures of compound 22
were designed using Chem. Draw 3D Ultra 11.0 software.
Using compute module to perform Gasteiger–Hückel, char-
ges of ligands were assigned. The molecular charged struc-
ture was energetically minimized by using AMBER with
100 iterations and a minimum RMS gradient of 0.10. The
template (PDB code: 2A5R) was obtained from the RCSB
protein data bank.
3 | CONCLUSION
A series of new β-substituted porphyrin conjugates
embedded with N-containing heterocycles derivatives
were synthesized from condensation reaction of
3-nitropyrrole with benzaldehyde in good yield, which
followed by reduction to its corresponding amino deriva-
tive (7). Cyanoacetamide (8) was achieved by heating
compound 7 with cyanoacetic acid in presence of drops
of acetic anhydride with the hope of discovering a new
structure that leads to serving as potent antitumor agents.
Some β-substituted porphyrins were screened for them
in vitro biological activities showed good antitumor activ-
ities. Compound 22 displayed very strong activity toward
all tested cell lines with an IC50 value of 9.62 ± 0.9, 5.16
± 1.4, and 5.05 ± 1.6 μg/ml. The obtained results may be
related to the presence of four sets of disubstituted amino
2
.2.4 | Preparation of the telomerase protein
The starting coordinates of the X-ray crystal structure of a
complex tetra(4-n-methylpyridyl) porphyrin with monomeric
parallel-stranded DNA Tetraplex (PDB code 2A5R: in com-
plex with the POH 25A) that retrieved from the RCSB protein
data bank of Brookhaven National Laboratory (Figure 1).
2.2.5 | Porphyrin interaction with
telomerase
The availability of a high-resolution crystallographic
structure of the human telomerase enzyme facilitated the

8
MASARET
C -H), 8.97 (s, 1H, N-H), 9.14 (s, 1H, C -H), 9.74 (s, 1H, N-
1
3
18
13
H); C NMR (DMSO-d ): δ (ppm): 103.1, 109.1, 116.7, 119.2
6
(C2), 125.5, 127.8, 128.6, 129.2, 132.1, 134.6, 135.7, 136.7,
1
38.5, 142.4 (C ), 150.1, 152.1 (C and C ), 156.8, 161.1. MS
12
7
17
+
+
(EI, 70 eV) m/z (%) = 794 (M , 100), 795 (M + 1, 50). Anal
calcd for C H N O (794.74): C, 66.50; H, 3.30; N, 14.10%.
44 26 8 8
Found: C, 66.22; H, 3.16; N, 13.95%.
Synthesis of 2,7,12,17-tetraamino-5,10,15,20-
tetraphenylporphyrin (7)
The reduction of compound 6 was conducted according
FIGURE 2 Top view of the docked compound 22 where two of
the phenyl groups and two the substituted pyridines merged out to
seal off the groove entry
to the reported work [29,30].
ꢀ
ꢁ1
62% yield; mp. < (300) C; IR (KBr): ν/cm = 3410
1
(
NH ), 3100 (NH); H NMR (DMSO-d ): δ (ppm): 3.83 (s,
2
6
groups meta to each other exposed out to the celling of
the DNA groove enhanced the hydrophilic recognition.
2H, C -NH ), 4.79 (s, 4H, C -NH , C -NH ), 4.98 (s, 1H,
2 2 7 2 17 2
C -H), 5.19 (s, 1H, C -H), 6.35 (s, 1H, C -NH ), 6.58 (s,
8
13
3
2
1
H, C -H), 6.79 (s, 2H, C -NH ), 7.17–7.41 (m, 20H, Ar-
18
13
12
2
H). C NMR (DMSO-d ): δ (ppm): 101.5, 103.1, 104.8,
6
4
4
| EXPERIMENTAL
.1 | Chemistry
105.1, 124.2, 127.8, 127.9, 128.6, 129.2, 132.1, 134.4, 135.7,
1
36.7, 137.5, 142.4, 144.8, 150.1, 155.7, 157.1, 161.1. MS
+
+
(EI, 70 eV) m/z (%) = 674 (M , 100), 675 (M + 1, 47).
Anal calcd for C H N (674.81): C, 78.32; H, 5.08; N,
44
34 8
Preparation of 1-(triisopropylsilyl) pyrrole (3)
16.61%. Found: C, 78.11; H, 4.98; N, 16.55%.
Compound 3 was obtained as previously reported [23],
ꢀ
ꢀ
0
00 000
boiling point (120) C/10 mm. (Lit. (125) C/11 mm,
Synthesis of N,N ,N ,N -(5,10,15,20-
ꢀ
mp. (5) C [23]).
tetraphenylporphyrin-2,7,12,17-tetrayl)tetrakis
(2-cyanoacetamide) (8)
ꢀ
ꢁ1
Preparation of 3-nitro-1-(triisopropylsilyl)
pyrrole (4)
78% yield; mp. < (300) C; IR (KBr): ν/cm = 3300, 3150
1
(NH), 2220 (CN), 1685 (CO), 1615 (C=N), 1595 (C=C); H
NMR (DMSO-d ): δ (ppm): 3.50 (s, 8H, CH ), 5.50 (s, 1H,
6
2
Compound 4 was obtained as previously reported,
mp. (50) C (Lit. 52–54 C [23]).
C -H), 5.77 (s, 1H, C -H), 6.38 (s, 1H, C -H), 7.24–7.48 (m,
8
13
3
ꢀ
ꢀ
20H, Ar-H + 1H, C -H), 8.38 (s, 1H, C -NH), 8.88 (s, 1H,
18 2
endocyclic NH), 9.38 (s, 2H, C -NH + C -NH), 9.50 (s, 1H,
7
17
1
3
endocyclic NH), 10.58 (s, 1H, C -NH). C NMR (DMSO-
12
Preparation of 3-nitro pyrrole (5)
d6): δ (ppm): 25.3, 25.5, 100.9, 101.1, 103.5, 103.7, 119.1,
22.5, 125.7, 127.9, 128.6, 129.7, 131.8, 132.1, 133.6, 134.4,
135.6, 136.7, 142.4, 150.1, 151.9, 157.5, 161.1, 167.3, 167.5.
1
It was prepared by desilylation of compound 4 as
ꢀ
+
+
described in previous work mp. (100) C, in 70% yield
MS (EI, 70 eV) m/z (%) = 942 (M , 100), 943 (M + 1, 60).
ꢀ
(
Lit. 95–96 C [23]).
Anal calcd for C H N O (943): C, 71.33; H, 4.06; N,
56 38 12 4
17.82%. Found: C, 71.21; H, 3.98; N, 17.66%.
Synthesis of 2,7,12,17-tetranitro-5,10,15,20-
tetraphenylporphyrin (6)
0
00 000
Synthesis of N,N ,N ,N -(5,10,15,20-
tetraphenylporphyrin-2,7,12,17-tetrayl)tetrakis
(2-amino-5,7-dimethyl-1,8-naphthyridine-
3-carboxamide) (10)
It was prepared according to Fadda et al. [27,28] method.
ꢀ
ꢁ1
Yield 72%; mp. < (300) C; IR (KBr): ν/cm = 3150
(
NH), 1610 (C=N), 1590 (C=C), 1530, 1350 (symm., asymm.
1
NO2); H NMR (DMSO-d ): δ (ppm): 6.61 (s, 1H, C -
Refluxing compound 8 (0.01 mol) with 2-amino-4,-
6-dimethylnicotenaldehyde (9) (0.04 mol) in dry ethanol
6
3
H),7.15–7.70 (m, 20 H, Ar-H), 7.54 (s, 1H, C -H), 7.74 (s, 1H,
8

MASARET
9
(20 ml) and piperdine as a catalyst for 8 h. The reaction
(ppm): 5.63 (s, 1H, C -H pyrrole), 5.85 (s, 1H, C -H pyr-
8
13
was coole and the obtained solid product was collected
role), 6.25 (s, 8H, 4NH ), 6.38 (s, 1H, C -H pyrrole), 7.11–
2
3
and recrystallized from ethanol to give 10.
7.38 (m, 36H, Ar-H), 7.55 (s, 1H, C -H pyrrole), 8.09 (d,
18
ꢀ
ꢁ1
6
8% yield; mp. < (300) C; IR (KBr): ν/cm = 3410
4H, Ar-H), 8.31 (s, 4H, C -H quinoline), 8.63 (s, 1H, C -
4 2
(
NH ), 3300 (NH br.), 1680 (CO), 1620 (C=N), 1600 (C=C);
NH), 8.85 (s, 1H, endocyclic NH), 9.25 (s, 2H, C -NH
2
7
1
H NMR (DMSO-d ): δ (ppm): 2.48 (s, 12H, 4CH ), 2.88 (s,
1
+ C -NH), 9.77 (s, 1H, endocyclic NH), 10.75 (s, 1H,
6
3
17
13
2H, 4CH ), 5.51 (s, 1H, C -H pyrrole), 5.77 (s, 1H, C -H pyr-
C -NH). C NMR (DMSO-d ): δ (ppm): 103.5, 103.8,
12 6
3
8
13
role), 6.27 (s, 8H, 4NH ), 6.51 (s, 1H, C -H pyrrole), 7.24–7.27
105.8, 106.1, 120.2, 122.8, 122.9, 124.3, 125.0, 127.6, 128.8,
131.3, 131.6, 132.0, 134.4, 135.8, 136.8, 137.4, 137.5, 142.5,
146.6, 150.2, 150.8, 155.5, 161.3, 163.8, 164.2, 164.5. Anal
calcd for C H N O (1355.50): C, 74.43; H, 4.31; N,
2
3
(
m, 24H, 20Ar-H + 4C -H naphthyridine), 7.45 (s, 1H, C -H
3 18
pyrrole), 8.11 (s, 4H, 4C -H naphthyridine), 8.48 (s, 1H, C -
5
2
NH), 8.88 (s, 1H, endocyclic NH), 9.55 (s, 2H, C -NH + C -
7
17
84 58 16 4
1
3
NH), 9.65 (s, 1H, endocyclic NH), 11.00 (s, 1H, C -NH).
C
16.53%. Found: C, 74.15; H, 4.27; N, 16.45%.
12
NMR (DMSO-d ): δ (ppm): 19.5, 24.2, 103.5, 106.1, 111.2,
6
1
1
1
15.2, 122.5, 124.4, 127.8, 128.6, 131.9, 134.4, 135.7, 136.7,
37.4, 139.4, 142.4, 145.8, 150.5, 155.7, 156.1, 158.5, 161.4,
64.1. Anal calcd for C H N O (1471.66): C, 71.82; H,
0
00 000
Synthesis of N,N ,N ,N -(5,10,15,20-
tetraphenylporphyrin-2,7,12,17-tetrayl)tetrakis
(7,7-dimethyl-2,5-dioxo-1,2,5,6,7,8-
88 70 20 4
4.79; N, 19.04%. Found: C, 71.71; H, 4.72; N, 18.95%.
hexahydroquinoline-3-carboxamide) (13)
0
00
000
00 000
Synthesis of (2E,2 E,2 E,2 E)-N,N',N ,N -(5,10,
5,20-tetraphenylporphyrin-2,7,12,17-tetrayl)
A mixture of compound 8 (0.01 mol) and ([2-dimeth-
ylamino] methylene)-5,5-dimethylcyclohexane-1,3-dione
(0.04 mol) was heated under microwave condition for
1
tetrakis(2-cyano-3-[2-nitrophenyl]
ꢀ
acrylamide) (11)
12 min (100 C). The reaction was cooled, collected, and
recrystallized from ethanol to give 13.
71% yield; mp. < (300) C; IR (KBr): ν/cm = 3330
(NH br.), 1725 (CO ketonic), 1687 (CO amidic); H NMR
ꢀ
ꢁ1
1
Heating of compound 8 (0.01 mol) and 2-nitrobenzaldehyde
0.04 mol) in absolute ethanol (20 ml) and piperdine as
(
catalyst (4 drops) for 6 h. The reaction was cooled, col-
(DMSO-d ): δ (ppm): 1.11 (s, 24H, 8 CH ), 2.27 (s, 8H,
6
3
lected, and recrystallized from ethanol to give 11.
4 CH ),2.85 (s, 8H, 4 CH ), 5.63 (s, 1H, C -H pyrrole),
2 2 8
5.85 (s, 1H, C -H pyrrole), 6.38 (s, 1H, C -H pyr-
13 3
ꢀ
ꢁ1
78% yield; mp. (295) C; IR (KBr): ν/cm = 3310 (NH),
1
2218 (CN), 1678 (CO), 1535, 1350 (symm., asymm. NO ); H
role), 7.11–7.27 (m, 20H, Ar-H), 7.38 (s, 1H, C -H pyr-
2
18
NMR (DMSO-d ): δ (ppm): 5.63 (s, 1H, C -H pyrrole), 5.85
role), 7.85 (s, 4H, C -H tetrahydro quinoline), 8.38 (s, 1H,
6
8
4
(
s, 1H, C -H pyrrole), 6.38 (s, 1H, C -H pyrrole), 7.11–7.95
C -NH), 8.85 (s, 1H, endocyclic NH), 9.25 (s, 2H, C -NH
13
3
2
7
(m, 36H, Ar-H), 7.57 (s, 1H, C -H pyrrole), 8.38 (s, 1H, C -
+ C -NH), 9.77 (s, 1H, endocyclic NH), 10.75 (s, 1H,
17
18
2
13
NH), 8.77 (s, 1H, 4C-H olefinic), 8.85 (s, 1H, endocyclic NH),
.25 (s, 2H, C -NH + C -NH), 9.77 (s, 1H, endocyclic NH),
C -NH), 12.58 (s, 4H, 4 NH). C NMR (DMSO-d ): δ
12 6
9
1
1
1
1
1
(ppm): 27.2 (8CH ), 32.5, 41.7 (4CH ), 42.6 (4CH ), 103.1,
3 2 2
7
17
13
0.75 (s, 1H, C -NH). C NMR (DMSO-d ): δ (ppm): 103.1,
103.5, 105.7, 106.2, 117.1, 122.8, 124.3, 127.6, 127.7, 128.6,
131.4, 131.6, 132.1, 134.3, 135.6, 136.6, 137.4, 142.3, 150.1,
150.3, 150.6, 153.7, 155.7, 161.1, 161.5, 162.5, 162.9, 163.3,
194.4. Anal calcd for C H N O (1543.71): C, 71.58; H,
1
2
6
03.7, 105.9, 106.1, 106.9, 115.8, 122.8, 123.8, 124.3, 127.9,
28.6, 128.8, 130.9, 131.8, 132.1, 134.4, 134.7, 135.6, 136.7,
37.4, 142.3, 147.7, 150.1, 150.6, 153.4, 155.7, 161.1, 162.9,
63.3. Anal calcd for C H N O (1475.42): C, 68.38; H,
92
78 12 12
5.09; N, 10.89%. Found: C, 71.44; H, 4.98; N, 10.76%.
84 50 16 12
3.42; N, 15.19%. Found: C, 68.24; H, 3.13; N, 15.01%.
0
00 000
Synthesis of 1,1 ,1 ,1 -(5,10,15,20-
0
00 000
Synthesis of N,N ,N ,N -(5,10,15,20-
tetraphenylporphyrin-2,7,12,17-tetrayl)tetrakis
(2,5-dioxo-4-phenyl-2,5-dihydro-1H-indeno
[1,2-b]pyridine-3-carbonitrile) (15)
tetraphenylporphyrin-2,7,12,17-tetrayl)tetrakis
2-aminoquinoline-3-carboxamide) (12)
(
Heating of compound 11 (0.01 mol) and Fe (catalytic
amount) in presence of glacial acetic acid (20 ml) for 5 h,
The reaction was cooled, collected, and recrystallized
from ethanol to give 12.
To a stirred solution of compound 8 (0.01 mol) and
2-(1-phyenylethylidene)-indane-1,3-dione
(14)
(0.04 mol) in presence of benzene (20 ml) and ammo-
nium acetate (0.5 g) were refluxed for 8 h. The reac-
tion was cooled, collected, and recrystallized from
ethanol to give 15.
ꢀ
ꢁ1
5
8% yield; mp. < (300) C; IR (KBr): ν/cm = 3420
1
2 6
(
NH ), 3250 (NH br.), 1682 (CO); H NMR (DMSO-d ): δ

10
MASARET
ꢀ
ꢁ1
6
2% yield; mp. < (300) C; IR (KBr): ν/cm = 3100
0.99 (s, 24H, 8 CH ), 3.11 (s, 8H, 8 CH), 5.63 (s, 1H, C -H
3
8
(
NH), 2215 (CN), 1729 (CO ketone), 1680 (CO amidic);
pyrrole), 5.85 (s, 1H, C -H pyrrole), 6.38 (s, 1H, C -H
13 3
1
H NMR (DMSO-d ): 5.63 (s, 1H, C -H pyrrole), 5.85 (s,
pyrrole), 7.11–7.27 (m, 20H, Ar-H), 7.38 (s, 1H, C -H
6
8
18
1
(
H, C -H pyrrole), 6.38 (s, 1H, C -H pyrrole), 7.11–7.38
pyrrole), 8.77 (s, 1H, endocyclic NH), 9.77 (s, 1H, endo-
13
3
13
m, 56H, Ar-H), 7.55 (s, 1H, C -H pyrrole), 8.85 (s, 1H,
cyclic NH). C NMR (DMSO-d ): 18.2, 18.3, 22.7 (8CH ),
6 3
18
13
endocyclic NH), 9.77 (s, 1H, endocyclic NH). C NMR
DMSO-d ): δ (ppm): 99.5, 103.1, 103.8, 106.9, 109.0,
43.6, 43.9, 100.9, 101.1, 103.1, 103.7, 116.8, 119.0, 122.5,
127.9, 128.8, 129.7, 131.9, 132.4, 133.6, 134.4, 135.5, 136.9,
142.5, 150.1, 151.9, 157.5, 161.1, 169.1, 169.5. Anal calcd
for C H N O (1371.45): C, 70.06; H, 4.26; N, 16.34%.
(
6
1
1
1
1
15.3, 115.8, 123.4, 124.0, 124.2, 126.2, 127.8, 127.9, 128.6,
28.4, 128.9, 132.3, 132.5, 134.2, 134.4, 135.6, 135.7, 136.5,
36.7, 137.4, 142.3, 145.0, 146.2, 150.1, 151.9, 155.7, 157.5,
57.9, 161.3, 169.4, 190.4. Anal calcd for C120H N O
12 8
80
58 16 8
Found: C, 69.95; H, 4.14; N, 16.22%.
62
(
3
1799.89): C, 80.08; H, 3.47; N, 9.34%. Found: C, 79.98; H,
.21; N, 9.27%.
0
00 000
Synthesis of N,N ,N ,N -(5,10,15,20-
tetraphenylporphyrin-2,7,12,17-tetrayl)tetrakis
(3-amino-3-thioxopropanamide) (20)
0
00 000
Synthesis of 1,1 ,1 ,1 -(5,10,15,20-
tetraphenylporphyrin-2,7,12,17-tetrayl)tetrakis
To compound 8 (0.001 mol) in pyridine (25 ml) and in
presence of a catalytic amount of triethylamine (4 drops),
(
6-amino-4-[methylthio]-2-oxo-1,2-
dihydropyridine-3,5-dicarbonitrile) (17)
H S gas is bubbled through with stirring until the weight
increased by (1.3 g). The reaction was cooled, collected,
2
A mixture of compound 8 (0.01 mol) and 2-(bis(met-
hylthio)methylene malononitrile (16) (0.04 mol) in dry
DMF (25 ml) in presence of anhydrous potassium car-
bonate (0.5 g) was refluxed for 8 h. The reaction was
cooled, collected, and recrystallized from ethanol to
give 17.
and recrystallized from ethanol to give 20.
ꢀ
ꢁ1
1
61% yield; mp. < (300) C; IR (KBr): ν/cm = 3380
(NH ), 3160 (NH br.), 1680 (CO), 1350 (C=S); H NMR
2
(DMSO-d ): 3.77 (s, 8H, 4 CH ), 5.63 (s, 1H, C -H pyr-
6
2
8
role), 5.85 (s, 1H, C -H pyrrole), 6.38 (s, 1H, C -H pyr-
13
3
role), 6.85 (s, 8H, 4 NH ), 7.11–7.28 (m, 20H, Ar-H), 7.37
2
ꢀ
ꢁ1
6
7% yield; mp. < (300) C; IR (KBr): ν/cm = 3440
(s, 1H, C -H pyrrole), 8.50 (s, 1H, C -NH), 8.85 (s, 1H,
18
2
1
(
NH ), 3200 (NH), 2219 (CN), 2217 (CN), 1685 (CO); H
endocyclic NH), 9.38 (s, 2H, C -NH + C -NH), 9.77 (s,
7 17
2
13
NMR (DMSO-d ): 2.80 (s, 12H, 4 SMe), 5.63 (s, 1H, C -H
1H, endocyclic NH), 10.85 (s, 1H, C -NH). C NMR
6
8
12
pyrrole), 5.85 (s, 1H, C -H pyrrole), 6.38 (s, 1H, C -H
(DMSO-d ): δ (ppm): 53.2, 101.1, 103.5, 119.2, 122.5,
13
3
6
pyrrole), 6.58 (s, 8H, 4 NH ), 7.11–7.27 (m, 20H, Ar-H),
127.8, 128.6, 129.6, 131.9, 133.4, 134.4, 135.7, 136.7, 142.4,
150.1, 151.9, 157.5, 161.1, 163.5, 167.5, 201.5. Anal calcd
2
7
.38 (s, 1H, C -H pyrrole), 8.77 (s, 1H, endocyclic NH),
18
13
9
.77 (s, 1H, endocyclic NH). C NMR (DMSO-d ): δ
for C H N O S (1079.30): C, 62.32; H, 4.30; N, 15.57%.
6
56 46 12 4 4
(
ppm): 14.4 (4CH -S), 61.8, 63.9, 89.2, 99.5, 103.1, 104.0,
Found: C, 62.26; H, 4.14; N, 15.44%.
3
1
1
1
15.8, 124.0, 124.3, 127.5, 127.9, 128.6, 132.4, 134.2, 134.4,
35.6, 136.7, 137.4, 142.3, 149.9, 150.3, 155.7, 157.5, 157.9,
60.7, 161.9, 175.9. Anal calcd for C H N O S
46 20 4 4
0
00 000
Synthesis of N,N ,N ,N -(5,10,15,20-
tetraphenylporphyrin-2,7,12,17-tetrayl)tetrakis
(4,6-dimethyl-2-thioxo-2,3-dihydropyridine-3-
carboxamide) (21)
76
(1431.58): C, 63.76; H, 3.24; N, 19.57%. Found: C,
6
3.65; H, 3.17; N, 19.44%.
0
00 000
Synthesis of 1,1 ,1 ,1 -(5,10,15,20-
A solution of compound 20 (0.01 mol) and pentane-2,-
4-dione (1 g, 0.04 mol) in absolute ethanol (30 ml) were
refluxed for 8 h in presence of a catalytic amount of
triethylamine (4 drops). The reaction was cooled, col-
lected, and recrystallized from ethanol to give 21.
tetraphenylporphyrin-2,7,12,17-tetrayl)tetrakis
4,4-dimethyl-2,6-dioxopiperidine-3,5-
dicarbonitrile) (19)
(
ꢀ
ꢁ1
Heating a mixture of 8 (0.01 mol) and ethyl 3-cyano-
-methyl-but-2-enate (18) (0.04 mol) in dry ethanol
73% yield; mp. < (300) C; IR (KBr): ν/cm = 3170
1
2
(NH br.), 1679 (CO), 1354 (C=S); H NMR (DMSO-d ):
6
(25 ml) and sodium ethoxide (1.36 g, 0.02 mol) for 7 h.
1.77 (s, 12H, 4 CH ), 2.27 (s, 12H, 4 CH ), 3.11 (s, 4H,
3
3
The reaction was cooled, collected, and recrystallized
4 CH), 5.63 (s, 1H, C -H pyrrole), 5.85 (s, 1H, C -H pyr-
8 13
from ethanol to give 19.
role), 5.95 (s, 4H, C -H pyridine), 6.38 (s, 1H, C -H pyr-
3 3
ꢀ
ꢁ1
73% yield; mp. < (300) C; IR (KBr): ν/cm = 3150
role), 7.11–7.27 (m, 20H, Ar-H), 7.38 (s, 1H, C -H
1
8
1
(NH br.), 2218 (CN), 1680 (CO); H NMR (DMSO-d ):
pyrrole), 8.50 (s, 1H, C -NH), 8.85 (s, 1H, endocyclic
6
2

MASARET
11
NH), 9.38 (s, 2H, C -NH + C -NH), 9.77 (s, 1H, endo-
61.5, 103.5, 106.1, 122.5, 123.6, 124.4, 127.8, 128.6, 129.6,
131.9, 134.4, 135.7, 136.7, 137.4, 138.6, 139.2, 141.9, 142.4,
150.5, 155.5, 158.9, 161.5, 162.5, 163.5. Anal calcd for
C104H N O (1807.96): C, 69.09; H, 4.79; N, 15.49%.
7
17
13
cyclic NH), 10.85 (s, 1H, C -NH). C NMR (DMSO-d6):
12
1
1
1
1
8.4 (4CH ), 19.9 (4CH ), 66.8, 67.7, 101.4, 103.2, 103.7,
3 3
09.2, 119.2, 122.2, 127.7, 128.6, 129.5, 131.9, 132.2, 133.6,
34.4, 135.6, 136.3, 136.7, 142.2, 150.4, 151.7, 157.5, 161.3,
67.3, 167.7, 174.0, 242.2 (4C=S). Anal calcd for
86
20 12
Found: C, 68.95; H, 4.66; N, 15.37%.
C H N O S (1335.65): C, 68.34; H, 4.68; N, 12.58%.
Found: C, 68.27; H, 4.57; N, 12.46%.
76
62 12 4 4
0
00 000
Synthesis of N,N ,N ,N -(5,10,15,20-
tetraphenylporphyrin-2,7,12,17-tetrayl)tetrakis
(
2-(6-cyano-4-oxo-5,7-diphenyl-3,5-dihydro-4H-
0
00 000
Synthesis of N,N ,N ,N -(5,10,15,20-
pyrano[2,3-d]pyrimidin-2-yl)acetamide) (27)
tetraphenylporphyrin-2,7,12,17-tetrayl)tetrakis
(
2-[4,6-diamino-3,5-dicyanopyridin-2-yl]
Heating a mixture of compound 8 (0.01 mol) and
2-amino-3-carbethoxy-5-cyno-4,6-diphenyl-4H-pyran (26)
acetamide) (22)
(
3.46 g, 0.01 mol) in presence of pyridine (25 ml) for 7 h.
A mixture of compound 8 (0.01 mol) and 2-aminoprop-
The reaction was cooled, collected, and recrystallized
1
-ene-1,1,3-tricarbonitrile
(malononitrile
dimer)
from ethanol to give 27.
ꢀ
ꢀ
ꢁ1
(0.04 mol) was heated in a pressure tube at 150 C in a
71% yield; mp. < (300) C; IR (KBr): ν/cm = 3200
silicon oil bath. The reaction was cooled, collected, and
(NH), 3150 (NH br.), 2218 (CN), 1685 (2 CO), 1620
1
recrystallized from ethanol to give 22.
(C=N), 1110 (C-O-C); H NMR (DMSO-d ): 3.11 (s, 8H,
6
ꢀ
ꢁ1
7
6% yield; mp. < (300) C; IR (KBr): ν/cm = 3370
4 CH ), 4.38 (s, 4H, 4 CH), 5.63 (s, 1H, NH endocyclic),
2
(
NH ), 3300 (NH br.), 2220 (CN), 2218 (CN), 1680 (CO);
5.77 (s, 1H, C -H pyrrole), 5.85 (s, 1H, C -H pyrrole),
2
8
13
1
H NMR (DMSO-d ): 3.98 (s, 8H, 4 CH ), 5.63 (s, 1H,
6.36 (s, 1H, C -H pyrrole), 7.11–7.38 (m, 60H, Ar-H), 7.55
6
2
3
C -H pyrrole), 5.85 (s, 1H, C -H pyrrole), 6.38 (s, 9H,
(s, 1H, C -H pyrrole), 9.28 (s, 2H, C -NH + C -NH),
8
13
18
7
17
C -H pyrrole +4 NH ), 6.85 (s, 8H, 4 NH ), 7.11–7.27 (m,
9.77 (s, 1H, C -NH), 12.58 (s, 4H, NH), 12.85 (s, 1H, NH
2
3
2
2
13
2
0H, Ar-H), 7.38 (s, 1H, C -H pyrrole), 8.50 (s, 1H, C -
endocyclic). C NMR (DMSO-d ): 33.5, 38.8, 39.5, 39.7,
18
2
6
NH), 8.85 (s, 1H, endocyclic NH), 9.38 (s, 2H, C -NH
92.3, 93.4, 98.0, 100.7, 104.1, 108.0, 114.0, 117.3, 119.7,
120.1, 121.5, 125.7, 127.6, 127.9, 128.8, 130.3, 133.5, 134.4,
135.6, 137.9, 139.0, 142.1, 142.3, 144.1, 146.6, 149.4, 156.4,
159.8, 161.9, 162.2, 164.0, 164.9, 167.3. Anal calcd for
C132H N O (2144.27): C, 73.74; H, 4.04; N, 13.06%.
7
+
C -NH), 9.77 (s, 1H, endocyclic NH), 10.85 (s, 1H,
17
C -NH). Anal calcd for C H N O (1471.50): C,
12
80 54 28 4
6
3
5.30; H, 3.70; N, 26.65%. Found: C, 65.27; H,
.56; N, 26.49%.
86
20 12
Found: C, 73.88; H, 3.97; N, 12.98%.
0
00 000
Synthesis of tetraethyl 5,5 ,5 ,5 -(((5,10,15,20-
tetraphenylporphyrin-2,7,12,17-tetrayl)tetrakis
(
0
00
000
00 000
Synthesis of (2E,2 E,2 E,2 E)-N,N',N ,N -
(5,10,15,20-tetraphenylporphyrin-
2,7,12,17-tetrayl)tetrakis(2-cyano-
3-[dimethylamino]acrylamide) (28)
azanediyl))tetrakis(carbonyl))tetrakis(6-imino-
-methyl-1-phenyl-1,6-dihydropyridazine-
4
3
-carboxylate) (25)
A solution of compound 8 (0.01 mol) and ethyl(z)-3-oxo-
-(2-phenylhydrazono)butanoate (23) (0.04 mol) was
refluxed in benzene-acetic acid mixture (20 ml, 1:1) for
h. The reaction was cooled, collected, and recrystallized
from ethanol to give 25.
9% yield; mp. < (300) C; IR (KBr): ν/cm = 3150
Amixtureof compound8(0.01 mol) anddimethylformamide-
dimethyl acetal (4.76 g, 0.04 mol) was refluxed for 8 h
in presence of dry xylene. The reaction was cooled,
collected, and recrystallized from ethanol to give 28.
2
8
ꢀ
ꢁ1
78% yield; mp. < (300) C; IR (KBr): ν/cm = 3150
ꢀ
ꢁ1
1
6
(NH br.), 2220 (CN), 1675 (CO amidic); H NMR (DMSO-
1
(
NH), 3100 (NH br.), 1700 (CO); H NMR (DMSO-d ):
d ): 3.11 (s, 24H, 8 CH ), 5.63 (s, 1H, C -H pyrrole), 5.85
6
6
3
8
1
4
.25 (t, 12H, 4CH ), 2.38 (s, 12H, 4 CH ), 4.11 (q, 8H,
(s, 1H, C -H pyrrole), 6.38 (s, 1H, C -H pyrrole), 7.11–
3
3
13
3
CH ), 5.63 (s, 1H, C -H pyrrole), 5.85 (s, 1H, C -H pyr-
7.27 (m, 20H, Ar-H), 7.38 (s, 1H, C -H pyrrole), 7.58 (s,
2
8
13
18
role), 6.38 (s, 1H, C -H pyrrole), 7.11–7.38 (m, 40H, Ar-
4H, =CH), 8.50 (s, 1H, C -NH), 8.77 (s, 1H, endocyclic
3
2
H), 7.57 (s, 1H, C -H pyrrole), 8.50 (s, 1H, C -NH), 8.85
NH), 9.38 (s, 2H, C -NH + C -NH), 9.66 (s, 1H, NH
18
2
7
17
13
(s, 1H, endocyclic NH), 9.27 (s, 4H, 4 C=NH), 9.38 (s, 2H,
endocyclic), 10.85 (s, 1H, C -NH). C NMR (DMSO-d6):
12
C -NH + C -NH), 9.77 (s, 1H, endocyclic NH), 10.85 (s,
43.5, 98.8, 103.1, 103.7, 105.9, 106.1, 114.6, 122.8, 124.3,
127.8, 127.9, 128.6, 131.8, 132.0, 134.4, 135.6, 136.4, 137.4,
7
17
13
1
H, C -NH). C NMR (DMSO-d ): δ (ppm): 10.8, 13.8,
12 6

12
MASARET
1
42.3, 150.1, 150.6, 155.7, 156.0, 161.1, 162.9, 163.3. Anal
ACKNOWLEDGMENTS
calcd for C H N O (1163.32): C, 70.21; H, 5.03; N,
The author is grateful to Prof. Dr. Ahmed A Fadda (Ph.
D., D.Sc.) Professor of Organic Chemistry, Faculty of Sci-
ence, Mansoura, Egypt, for suggesting the point of
research and his valuable discussion.
68
58 16 4
1
9.26%. Found: C, 70.11; H, 4.93; N, 19.12%.
0
00 000
Synthesis of N,N ,N ,N -(5,10,15,20-
tetraphenylporphyrin-2,7,12,17-tetrayl)tetrakis
DATA AVAILABILITY STATEMENT
The data that supports the findings of this study are avail-
able in the supplementary material of this article.
(
5-amino-2-phenylpyrazolo[1,5-a]pyrimidine-
-carboxamide) (29)
6
ORCID
A mixture of compound 28 (0.01 mol) was heated with
-phenyl-1H-pyrazol-5-amine (6.36 g, 0.04 mol) in pres-
Ghada S. Masaret https://orcid.org/0000-0001-5925-
3
7466
ence of DMF (25 ml) and 4 drops of piperdine for 8 h.
The reaction was cooled, collected, and recrystallized
from ethanol to give 29.
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SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of this
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