Phthalocyanines and related compounds: XLII. Synthesis of phenyl-substituted tetraazachlorins and tetraazabacteriochlorins

Article abstract of DOI:10.1134/S1070363206070280

New oxidation-resistant hexaphenyl-substituted tetramethyltetraazachlorin, its nickel complex, and tetraphenyl-substituted octamethyltetraazabacteriochlorin and octamethyltetraazaisobacteriochlorin nickel complexes were synthesized for the first time by mixed condensation of diphenylm aleonitrile with tetramethylsuccinonitrile in the presence of lithium dimethylaminoethoxide or nickel chloride. The products were characterized by electronic absorption, ¹H NMR, and mass spectra. Mixed condensation of diphenylsuccinonitrile with phthalonitrile in the presence of nickel chloride was found to give nickel complexes of phenylsubstituted benzo-fused tetraazaporphyrins rather than their hydrogenated derivatives. Pleiades Publishing, Inc., 2006.

Full text of DOI:10.1134/S1070363206070280

ISSN 1070-3632, Russian Journal of General Chemistry, 2006, Vol. 76, No. 7, pp. 1165 1169.
Pleiades Publishing, Inc., 2006.
Original Russian Text
E.A. Makarova, E.V. Dzyuina, E.A. Luk’yanets, 2006, published in Zhurnal Obshchei Khimii, 2006, Vol. 76, No. 7,
pp. 1213 1217.
Phthalocyanines and Related Compounds:
XLII.1 Synthesis of Phenyl-Substituted Tetraazachlorins
and Tetraazabacteriochlorins
E. A. Makarova, E. V. Dzyuina, and E. A. Luk’yanets
Research Institute of Organic Intermediate Products and Dyes,
ul. B. Sadovaya 1/4, Moscow, 123995, Russia
e-mail: rmeluk@co.ru
Received July 28, 2005
Abstract New oxidation-resistant hexaphenyl-substituted tetramethyltetraazachlorin, its nickel complex,
and tetraphenyl-substituted octamethyltetraazabacteriochlorin and octamethyltetraazaisobacteriochlorin nickel
complexes were synthesized for the first time by mixed condensation of diphenylmaleonitrile with tetra-
methylsuccinonitrile in the presence of lithium dimethylaminoethoxide or nickel chloride. The products were
1
characterized by electronic absorption, H NMR, and mass spectra. Mixed condensation of diphenylsuccino-
nitrile with phthalonitrile in the presence of nickel chloride was found to give nickel complexes of phenyl-
substituted benzo-fused tetraazaporphyrins rather than their hydrogenated derivatives.
DOI: 10.1134/S1070363206070280
Tetraazachlorins, tetraazabacteriochlorins, and tetra-
azaisobacteriochlorins are derivatives of 5,10,15,20-
tetraazaporphyrin hydrogenated at one or two quasi-
isolated double bonds in the neighboring or opposite
pyrrole fragments of the macroring. These compounds
attract a considerable interest from both theoretical
and practical viewpoints as a new class of so-called
functional dyes, i.e. dyes for nontraditional applica-
tions, in particular as second-generation photosensiti-
zers for photodynamic therapy of cancer due to their
strong absorption in the therapic window (red and
near IR region spectral region). Unlike their analogs
of the porphyrin series, chlorins, bacteriochlorins, and
isobacteriochlorins whose synthesis and properties
were the subjects of numerous studies, the title com-
pounds remained so far almost not studied, and no
data on their synthesis were available. As a result of
our studies performed in the recent years, we have
developed methods for synthesis of partially hydro-
genated tetraazaporphyrin derivatives. One of these
methods is based on [4+2]-[2, 3] and 1,3-cycloaddi-
tion [4] at the quasiisolated double bonds in a tetra-
azaporphyrin molecule, by analogy with the synthesis
of partially hydrogenated porphyrins [5]. An alterna-
tive method implies mixed condensation of phthalo-
gens with different degrees of saturation. We were the
first to use in these syntheses tetramethylsuccinonitrile
which is a vicinal aliphatic 1,2-dinitrile with the
cyano groups attached to quaternary carbon atoms.
By mixed condensation of aromatic ortho-dicar-
boxylic acid derivatives (dinitriles, anhydrides, and
imides) with tetramethylsuccinonitrile in the presence
of metal salts or lithium alkoxides were obtained
previously unknown linearly fused 2,3-naphthotetra-
azachlorins, -tetraazabacteriochlorins, and -tetraaza-
isobacteriochlorins, as well as angularly fused 1,2-
naphtho isomers [6 9]. Studies on photophysical
properties of the newly synthesized compounds
[10 13] showed that they may be interesting from the
viewpoint of practical applications.
In the present work we made an attempt to syn-
thesize new partially hydrogenated tetraazaporphyrin
derivatives by mixed condensation of diphenylmaleo-
nitrile with tetramethylsuccinonitrile. The reaction of
equimolar amounts of these compounds in boiling
quinoline in the presence of nickel(II) chloride and a
catalytic amount of ammonium molybdate gave hexa-
phenyltetramethyltetraazachlorin nickel complex I in
12.3% yield; in addition, (octaphenyltetraazaporphyri-
nato)nickel(II) was formed. Molecule I contains two
quaternary carbon atoms attached to methyl groups
which deviate from the macroring plane; therefore,
compound I is readily soluble in common organic
solvents, and it can readily be separated from (octa-
phenyltetraazaporphyrinato)nickel(II) by extraction
1
For communication XLI, see [1].
1165

1166
MAKAROVA et al.
with chloroform, followed by chromatographic puri-
fication on silica gel. It should be noted that the re-
action mixture also contained small amounts of tetra-
phenyloctamethyltetraazabacteriochlorin II and tetra-
phenyloctamethyltetraazaisobacteriochlorin III nickel
complexes which were detected by spectral methods.
When the molar ratio of the initial nitriles was raised
to 1:3, the yields of the latter increased to 4.1 and
3.9%, respectively, while the yield of chlorin I
reached 32.2%. As in the condensation of tetramethyl-
succinonitrile with phthalonitrile described previously
[8], further raising the tetramethylsuccinonit-
rile-to-diphenylmaleonitrile molar ratio variation
of the reaction time or temperature did not increase
the yield of compounds II and III. The presence of
geminal methyl groups in the macroring of the ob-
tained compounds improves their solubility in
common organic solvents and hampers their oxidation
to the corresponding tetraazaporphyrin derivatives;
therefore, they can be separated and purified by chro-
matography on silica gel. Metal-free hexaphenyltetra-
methyltetraazachlorin (IV) was formed in 3.8% yield
in the reaction of diphenylmaleonitrile with tetra-
methylsuccinonitrile at a molar ratio of 2:3 in boiling
dimethylaminoethanol in the presence of lithium di-
methylaminoethoxide (reaction time 4 h).
LiOCH2CH2N(CH3)2
+
2-dimethylaminoethanol,
+
IV
NiCl2,
quinoline,
+
+
+
I
II
III
The structure of the isolated compounds was de-
termined on the basis of their elemental compositions
methyl protons, while isobacteriochlorin III displayed
two signals at 1.47 and 1.50 ppm, indicating mag-
netic nonequivalence of the corresponding methyl
groups in molecule III. The aromatic regions of the
1
1
and H NMR and mass spectra. The H NMR spec-
trum of chlorin I contained a singlet in the aliphatic
region at 1.79 ppm from the methyl protons, and in
the aromatic region we observed two multiplets at
7.25 7.59 (p-H, m-H) and 8.0 8.06 ppm (o-H) from
the phenyl groups. The signal intensity ratio was
2:3:2, which is consistent with the structure of chlo-
rin I. The two other nickel complexes were assigned
the structure with two saturated C C bonds in the
neighboring (isobacteriochlorin III) or opposite (bac-
teriochlorin II) pyrrole rings on the basis of their elec-
tronic absorption spectra and 1H NMR data. The
1H NMR spectra of both compounds showed no ap-
preciable differences. Bacteriochlorin II displayed two
multiplets at
7.25 7.55 (p-H, m-H) and 8.01
8.05 ppm (o-H), and in the spectrum of compound III
we observed two multiplets at 7.25 7.46 (p-H, m-H)
and 7.77 7.81 ppm (o-H). The signal intensity ratios
were 6:3:2 for the three signals of bacteriochlorin II
and 3:3:3:2 for the four signals of isobacteriochlorin
III; these data are very consistent with the assumed
structures.
1
aliphatic region of the H NMR spectrum of bacterio-
chlorin II contained one signal at 1.59 ppm from
The electronic absorption spectra of compounds
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PHTHALOCYANINES AND RELATED COMPOUNDS: XLII.
1167
I IV in organic solvents were examined in the range
log
5
from 250 to 1000 nm. As expected, all these com-
pounds are characterized by strong absorption in the
red and near IR regions (see figure). Metal-free chlo-
rin IV displayed a strong long-wave Q band which
was split into two components with different inten-
2
3
1
4
4
3
sities: Q1,
727 nm; Q2,
557 nm. Thus
max
max
2
hydrogenation of the -carbon atoms in one pyrrole
fragment of the octaphenyltetraazaporphyrin molecule
1
0
(
666, 600 nm [14]) leads to a red shift of the
max
long-wave Q1 band (by 60 nm) and blue shift of the
Q2 band (by 45 nm). The Q band in the spectra of
nickel complexes I and II is also split into two com-
ponents (unlike metal complexes of octaphenyltetra-
azaporphyrin) due to reduction of the molecular
symmetry from D4h to C2v and D2h as a result of
hydrogenation of one or two opposite pyrrole frag-
ments, respectively. The Q1 band has its maximum at
701 nm for complex I and at 866 nm for complex
400
600
800
1000
, nm
Electronic absorption spectra of compounds (1) I, (2) IV,
(3) II, and (4) III in chloroform.
argon atmosphere) gave a mixture of phenyl-substi-
tuted benzo-fused tetraazaporphyrin nickel complexes
instead of the expected hydrogenated derivatives.
Unfortunately, we failed to separate the products by
column chromatography because of their poor solu-
bility in common organic solvents. A small amount
of that mixture was separated by thin-layer chroma-
tography on Silufol UV-254 plates (toluene chloro-
form, 2:1). We thus isolated four fractions; on the
basis of the mass and electronic absorption spectra
and taking into account published data for phenyl-
substituted benzofused tetraazaporphyrin palladium
complexes [17], these fractions were identified as
nickel complexes of hexaphenylbenzotetraazapor-
II. Less intense Q2 band is located at
550 and
467 nm, respectively, and its intensity decreases in
going from tetraazachlorin I to tetraazabacteriochlorin
II. The Q1/Q2 intensity ratio is 1.7 for compound I
and 4.8 for bacteriochlorin II. The magnitude of
Q1/Q2 splitting for bacteriochlorin II is 9866 cm ,
which is twice as large as the corresponding parameter
for chlorin I (4763 cm ). In the electronic absorption
spectrum of isobacteriochlorin III which (like chlorin
I has a C2v symmetry) we observed no splitting of the
1
1
Q band (
642 nm). An analogous spectral pattern
was typicaml aoxf other tetraazaisobacteriochlorin deriva-
tives which were studied previously [3, 8, 9] (the
results of quantum-chemical calculations, magnetic
circular dichroism spectra, and band resolution pro-
cedure revealed a low-intense Q2 band for these
derivatives). In the short-wave region of the electronic
absorption spectra of compounds I IV, a B band with
a lower intensity was present; this band is related to
the Soret band in the series of porphyrin, and its posi-
tion and intensity did not change to an appreciable
extent in going from tetraazaporphyrin to tetraaza-
chlorin and tetraazabacteriochlorin.
phyrin (
655, 613 nm), tetraphenyldibenzotetra-
azaporphymrianx with oppositely arranged benzene rings
(
693, 592 nm), its isomer with neighboring
bemnzaxene rings (
638 nm), and diphenyltribenzo-
673, 630 nm). In the elec-
tetraazaporphyrinm(ax
tronic absorption spemctarxum of the reaction mixture we
observed an absorption band with its maximum at
727 nm, which is likely to belong to intermediately
formed diphenyltribenzotetraazachlorin; however, no
such band was detected after chromatographic separa-
tion. We can conclude that benzo-fused derivatives of
tetraazachlorin and tetraazabacteriochlorin are less
stable to oxidation than unsubstituted tetraazachlorin
[18] and dibenzobarrelenosubstituted analogs [2]; the
reasons are extension of the macroring system due
to fusion of benzene rings and the presence of hydro-
gen atoms at the sp3-carbon atoms (unlike oxidation-
resistant exhaustively methylated analogs) [6 8].
We also made an attempt to synthesize partially
hydrogenated tetraazaporphyrin derivatives having
phenyl substituents at the sp3-carbon atoms. As shown
previously [15, 16], the reaction of pyrrolidine-2,5-
diimine with isoindole-1,3-diimine or 4-tert-butyliso-
indole-1,3-diimine leads to the formation of benzo-
fused tetraazaporphyrins. We performed mixed con-
densation of diphenylsuccinonitrile as a saturated
component with phthalonitrile. However, the reaction
between these compounds taken at a ratio of 1:1 to
2:1 in the presence of NiCl2 and a catalytic amount
of ammonium molybdate (boiling quinoline, 1 h,
EXPERIMENTAL
The electronic absorption spectra were measured
on a Hewlett Packard 8453 spectrophotometer using
10-mm rectangular quartz cells; solutions with a
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 7 2006

1168
MAKAROVA et al.
5
1
concentration of about 10 M were examined. The
1H NMR spectra were recorded on a Bruker WM-250
instrument (250.13 MHz) from solutions in CDCl3.
The mass spectra were obtained on a Finnigan-LCQ/
Electrospray spectrometer.
(4.39). H NMR spectrum, , ppm: 1.59 s (24H, Me),
7.25 7.55 m (12H, p-H, m-H), 8.0 8.05 m (8H, o-H).
Found, %: C 71.99, 72.15; H 5.80, 5.79; N 14.03,
13.96. C48H44N8Ni. Calculated, %: C 72.83; H 5.60;
N 14.15.
2,3-Diphenylmaleonitrile [14], 2,3-diphenylsuccino-
nitrile [19], and tetramethylsuccinonitrile [20] were
synthesized by known methods.
Tetraazaisobacteriochlorin III. Electronic absorp-
tion spectrum (CHCl3), max, nm (log ): 642 (4.92),
1
594 sh (4.24), 520 (4.15), 486 (4.16), 312 (4.53). H
NMR spectrum, , ppm: 1.47 s (12H, Me), 1.50 s
(12H, Me), 7.25 7.46 m (12H, p-H, m-H), 7.77
7.81 m (8H, o-H). Found, %: C 73.13, 72.98; H 5.56,
5.83; N 13.25, 13.38. C48H44N8Ni. Calculated, %: C
72.83; H 5.60; N 14.15.
(2,2,3,3-Tetramethyl-7,8,12,13,17,18-hexaphe-
nyltetraazachlorinato)nickel(II) (I), (2,2,3,3,12,12,
13,13-octamethyl-7,8,17,18-tetraphenyltetraazabac-
teriochlorinato)nickel(II) (II), and 2,2,3,3,7,7,8,8-
octamethyl-12,13,17,18-tetraphenyltetraazaisobac-
teriochlorinato)nickel(II) (III). a. Nitrile molar ratio
1:1. A mixture of 0.490 g of tetramethylsuccinonitrile,
0.820 g of diphenylmaleonitrile, 0.470 g of anhydrous
NiCl2, and 0.003 g of ammonium molybdate in 5 ml
of quinoline was heated for 3 h at the boiling point
under stirring. The mixture was cooled and diluted
with 50% aqueous acetone, and the precipitate was
filtered off, washed with 50% aqueous acetone and
water and dried in air. The product was thoroughly
ground and extracted with chloroform, and the extract
was subjected to chromatography on silica gel using
hexane chloroform (1:1) as eluent. A lilac fraction
(Rf 0.35, Silufol UV-254, hexane chloroform, 1:1)
was collected; removal of the solvent gave 0.129 g
(12.3%) of compound I. Electronic absorption spec-
trum (CHCl3), max, nm (log ): 701 (4.80), 645 sh
2,2,3,3-Tetramethyl-7,8,12,13,17,18-hexaphenyl-
tetraazachlorin (IV). Metallic lithium, 0.010 g, was
dissolved on heating in 20 ml of 2-dimethylamino-
ethanol, the solution was cooled to room temperature,
and a mixture of 0.820 g of diphenylmaleonitrile and
0.490 g of tetramethylsuccinonitrile was added. The
mixture was slowly heated to the boiling point under
stirring, and was then heated for 4 h under reflux. The
mixture was cooled and diluted with 100 ml of water,
and the precipitate was filtered off, washed in succes-
sion with hot water and 50% aqueous ethanol, and
dried in air. The product was ground and extracted
first with ethanol to remove impurities and then with
chloroform. Chromatographic purification on silica
gel gave 0.025 g (3.8%) of compound IV. Mass spec-
trum, m/z: 829.2 (M+). Electronic absorption spectrum
(CHCl3), max, nm (log ): 727 (4.63), 691 sh (3.85),
662 sh (3.69), 557 (4.10), 488 (3.72), 371 (4.32), 336
(4.33). Found, %: C 78.45, 78.67; H 5.66, 5.40; N
12.76, 12.68. C56H44N8 H2O. Calculated, %: C 79.41;
H 5.47; N 13.23.
1
(4.28), 550 (4.44), 355 (4.48), 306 (4.59). H NMR
spectrum, , ppm: 1.70 s (12H, Me), 7.25 7.59 m
(18H, p-H, m-H), 8.01 8.06 m (12H, o-H). Found, %:
C 76.76, 76.57; H 5.11, 5.33; N 12.67, 12.55.
C56H42N8Ni. Calculated, %: C 75.94; H 4.78; N 12.65.
b. Nitrile molar ratio 1:3. A mixture of 0.490 g of
tetramethylsuccinonitrile, 0.276 g of diphenylmaleo-
nitrile, 0.470 g of anhydrous NiCl2, and 0.003 g of
ammonium molybdate in 5 ml of quinoline was
heated for 3 h at the boiling point under stirring. The
mixture was then treated as described above in a.
Three fractions were collected. The first fraction
(green brown, Rf 0.51, Silufol UV-254, hexane
chloroform, 1:1) contained 0.018 g (4.1%) of com-
pound II. The second fraction (blue, Rf 0.37, Silufol
UV-254, hexane chloroform, 1:1) contained 0.017 g
(3.9%) of compound III which was isolated by re-
peated chromatography on silica gel using hexane
chloroform (1:1) as eluent. The third fraction (lilac,
Rf 0.35, Silufol UV-254, hexane chloroform, 1:1)
contained 0.144 g (32.2%) of compound I.
ACKNOWLEDGMENTS
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 04-03-32533).
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