The synthesis, photochemical and photophysical properties of zinc aryloxy- and alkyloxy azaphthalocyanines

Article abstract of DOI:10.1016/j.dyepig.2010.03.023

Octasubstituted zinc tetrapyrazinoporphyrazines bearing butyloxy, octyloxy, 2,6-diisopropylphenoxy and 4-(hydroxymethyl)phenoxy substituents were synthesized from the corresponding 5,6-disubstituted pyrazine-2,3-dicarbonitriles using Zn(quinoline)₂Cl₂ in yields varying from 14 to 44%. The reaction procedure proved to be efficient for the synthesis of both alkyloxy- and aryloxy- substituted zinc tetrapyrazinoporphyrazines and did not require strictly anhydrous conditions. Optimal cyclotetramerization conditions were identified for each derivative, in terms of reaction temperature, as overheating cleaved the ether bond leaving a vacant OH group on the macrocycle. The photochemical and photophysical properties of the synthesized compounds were investigated in pyridine. Singlet oxygen quantum yields (Φ_Δ) ranged from 0.49 to 0.61 and high fluorescence quantum yields (Φ_F) of ～0.30 were observed for non-aggregated compounds.

Full text of DOI:10.1016/j.dyepig.2010.03.023

Dyes and Pigments 87 (2010) 173e179
Contents lists available at ScienceDirect
Dyes and Pigments
journal homepage: www.elsevier.com/locate/dyepig
The synthesis, photochemical and photophysical properties
of zinc aryloxy- and alkyloxy azaphthalocyanines
ꢁ
*
ꢀ ꢁ
Veronika Novakova, Petr Zimcik , Miroslav Miletin, Petr Vujtech, Sárka Franzová
Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Heyrovskeho 1203,
Hradec Kralove 50005, Czech Republic
a r t i c l e i n f o
a b s t r a c t
Article history:
Octasubstituted zinc tetrapyrazinoporphyrazines bearing butyloxy, octyloxy, 2,6-diisopropylphenoxy and
4-(hydroxymethyl)phenoxy substituents were synthesized from the corresponding 5,6-disubstituted
pyrazine-2,3-dicarbonitriles using Zn(quinoline)2Cl2 in yields varying from 14 to 44%. The reaction
procedure proved to be efficient for the synthesis of both alkyloxy- and aryloxy- substituted zinc tet-
rapyrazinoporphyrazines and did not require strictly anhydrous conditions. Optimal cyclotetramerization
conditions were identified for each derivative, in terms of reaction temperature, as overheating cleaved
the ether bond leaving a vacant OH group on the macrocycle. The photochemical and photophysical
properties of the synthesized compounds were investigated in pyridine. Singlet oxygen quantum yields
Received 30 October 2009
Received in revised form
15 March 2010
Accepted 16 March 2010
Available online 27 March 2010
Keywords:
Aryloxy substitution
Fluorescence
(FD) ranged from 0.49 to 0.61 and high fluorescence quantum yields (FF) of w0.30 were observed for
non-aggregated compounds.
Phthalocyanine
Ó 2010 Elsevier Ltd. All rights reserved.
Singlet oxygen
Tetrapyrazinoporphyrazine
Transetherification
1. Introduction
the photochemical and photophysical properties of the compounds
has not attracted attention.
Phthalocyanines (Pc) belong to a thoroughly investigated class
of dye that enjoys widespread use in a variety of applications [1,2].
Azaphthalocyanines (AzaPc) are aza-analogs of Pc in which some of
the carbon atoms in the Pc macrocycle are replaced by nitrogens.
Tetrapyrazinoporphyrazines (TPyPz) belonging to the AzaPc sub-
group have attracted attention of researchers owing to their
promising photosensitizing [3], fluorescent [4], non-linear optical
[5] and oxidative [6] properties. The photochemical and photo-
physical properties of TPyPz are known to be altered significantly
by different peripheral substitutions. Whilst the singlet oxygen and
fluorescence quantum yields have been investigated for alkylsul-
fanyl [7], alkylamino [8], aryl [9] or heteroaryl [10] substituted
derivatives, this has not been the case for TPyPz with an oxygen
linkage between the macrocycle and peripheral substituents.
Despite the extensive investigation of aryloxy substituted Pc
[11e19], studies of aryloxy as well as alkyloxy TPyPz are rare
because of the lack of suitable synthetic procedures. Whilst the
synthesis of aryloxy TPyPz was resolved by two research groups
only recently [20,21] and the aggregation, crystal structure and
UVevis spectra of the compounds studied in detail [22e24],
This paper concerns the synthesis of alkyloxy- and aryloxy-
substituted zinc TPyPz (ZnTPyPz) and their singlet oxygen
production and fluorescence. The peripheral substituents in the
investigated compounds were chosen to cover both alkyloxy- and
aryloxy- derivatives with the intention of presenting a synthetic
procedure that is suitable for both types of substitution.
2. Experimental
All organic solvents were of analytical grade. Anhydrous octanol
was stored over magnesium and distilled prior to use. TLC was per-
formed on Merck aluminium sheets coated with silica gel 60 F254.
Merck Kieselgel 60 (0.040e0.063 mm) was used for column chro-
matography. Infrared spectra were measured on an IR-Spectrometer
Nicolet Impact 400 (in KBr pellets) or Nicolet 6700 (in ATR mode). 1H
and 13C NMR spectra were recorded on a Varian Mercury e Vx BB 300
(299.95 MHz e 1H and 75.43 MHz e 13C); reported chemical shifts are
relative to Me4Si. Elemental analysis was carried out using an Auto-
matic Microanalyser EA1110CE (Fisons Instruments S.p.A., Milano,
Italy). UVevis spectra were recorded on a UV-2401PC spectropho-
tometer (Shimadzu Europa, GmbH, Duisburg, Germany). Fluores-
cence spectra were obtained using an AMINCO-Bowman Series
* Corresponding author. Tel.: þ420 495067257; fax: þ420 495067167.
E-mail address: petr.zimcik@faf.cuni.cz (P. Zimcik).
2
luminescence spectrometer (SLM-Aminco, Urbana, IL, USA).
0143-7208/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.dyepig.2010.03.023

174
V. Novakova et al. / Dyes and Pigments 87 (2010) 173e179
The MALDI-TOF mass spectra were collected on a Voyager-DE STR
mass spectrometer (Applied Biosystems, Framingham, MA, USA)
calibrated externally with a five-point calibration procedure using
Peptide Calibration Mix1 (LaserBio Labs, Sophia-Antipolis, France). A
solution of TPyPz in DCM (approximate concentration
1 ꢀ 10ꢁ5 mol Lꢁ1, 1.5 ꢀ 10ꢁ3 mL) was mixed with trans-2-[3-(4-tert-
butylphenyl)-2-methyl-2-propenylidene]-malononitrile matrix in
DCM (0.01 mL, 1 mg/0.5 mL) and spotted on the plate.
114.3, 121.9, 124.5, 128.9, 142.1, 151.4, 153.3 ppm. IR (ATR):
nmax ¼ 3303, 2936, 2873, 2233 (CN), 1729, 1701, 1598, 1544, 1501,
1441, 1400, 1374, 1350, 1237, 1194, 1153, 1105, 1039, 1011, 941, 924,
858, 847 and 809 cmꢁ1. Elemental analysis calc. (%) for C20H14N4O4:
C, 64.17; H, 3.77; N, 14.97; found: C, 62.45; H, 4.25; N, 14.37.
2.1.4. Alternative preparation of 5,6-bis(4-(hydroxymethyl)
phenoxy)pyrazine-2,3-dicarbonitrile (5)
NaOH (100 mg, 2.5 mmol) was dissolved in water (20 mL) and
4-(hydroxymethyl)phenol (311 mg, 2.5 mmol) was added. The
suspension was sonicated and stirred for 20 min at room temper-
ature and ethanol (10 mL) was added to expedite solubilisation.
Thereafter, compound 1 (200 mg, 1.0 mmol) in tetrahydrofuran
(10 mL) was added dropwise and the ensuing solution was stirred
for 10 min at room temperature. Ethanol and tetrahydrofuran were
evaporated and the mixture was diluted with water (70 mL) and
extracted three times with ethylacetate (3 ꢀ 100 mL). The organic
layer was dried over anhydrous Na2SO4, filtered and evaporated
under reduced pressure to dryness. The mixture was purified by
column chromatography on silica with chloroform/acetone 10:1.
The two important fractions were isolated, one corresponding to 5
(Rf ¼ 0.15, white solid, 86 mg, 23%) and the second was 5,6-bis
(ethoxy)pyrazine-2,3-dicarbonitrile (Rf ¼ 0.79, a pale yellow solid,
89 mg, 41%; m.p. 112.2e113.0 ꢂC, lit.[28] 117e118 ꢂC). 1H NMR
2.1. Synthesis
5,6-Dichloropyrazine-2,3-dicarbonitrile (1) [25], 5,6-bis(butoxy)
pyrazine-2,3-dicarbonitrile (2) [26] and Zn(quinoline)2Cl2 (ZnQ2Cl2)
[27] were prepared according to published procedures.
2.1.1. 5,6-Bis(octyloxy)pyrazine-2,3-dicarbonitrile (3)
A solution of triethylamine (895 mg, 8.84 mmol) in anhydrous
octanol (6 mL) was stirred for 45 min at room temperature and
added dropwise to a suspension of 1 (800 mg, 4 mmol) in anhy-
drous octanol (25 mL). The suspension dissolved after approxi-
mately 15 min and stirring was continued for 60 min at room
temperature. Octanol was then removed under reduced pressure
and the crude product was purified by column chromatography on
silica using toluene/hexane 2:1 as eluent, to provide a yellow oil
(785 mg, 51%). 1H NMR (300 MHz, CDCl3, 25 ꢂC):
d
¼ 0.89 (t, 6 H,
(300 MHz, (CD3)2CO, 25 ꢂC):
d
¼ 1.43 (t, 6 H, J ¼ 7.1 Hz, CH3),
J ¼ 6.6 Hz, CH3), 1.25e1.45 (m, 20 H, CH2), 1.83 (p, 4 H, J ¼ 7.0 Hz,
4.54 ppm (q, 4 H, J ¼ 7.1 Hz, OCH2). 13C NMR (75 MHz, (CD3)2CO,
OCH2CH2) and 4.45 (t, 4 H, J ¼ 6.7 Hz, OCH2) ppm. 13C NMR (75 MHz,
25 ꢂC):
d
¼ 14.15, 65.82, 114.81, 123.34 and 153.16 ppm.
CDCl3, 25 ꢂC):
d
¼ 14.06, 22.61, 25.72, 28.16, 29.11 (4 carbons
according to rough integration), 31.72, 69.49, 113.49, 122.57 and
2.1.5. 2,3,9,10,16,17,23,24-Octakis(butoxy)-1,4,8,11,15,18,22,25-
151.95 ppm. IR (ATR): nmax ¼ 2953, 2924, 2855, 2236 (CN), 1549,
(octaaza)phthalocyanine zinc (II) (6)
1495, 1458, 1379, 1344, 1299, 1239, 948 cmꢁ1
.
Precursor 2 (80 mg, 0.29 mmol) and ZnQ2Cl2 (115 mg,
0.29 mmol) were mixed in a round bottom flask and heated at
190 ꢂC for 60 min. The crude product was dissolved in chloroform
(100 mL), filtered and the solvent removed under reduced pressure.
The solid was then washed with water/methanol 1:1 (300 mL),
adsorbed on silica and thoroughly washed with methanol (300 mL)
on a glass frit. Afterwards, the product was purified by column
chromatography on silica using chloroform as eluent to give a blue
solid (12 mg, 14%). NMR, IR, UVevis spectra showed the same
characteristics as described in the literature for this compound
prepared using different approach [26]. MS (MALDI-TOF) m/z 1160
[M]þ,1183 [M þ Na]þ,1199 [M þ K]þ, 2321 [2M]þ, 2344 [2M þ Na]þ,
2360 [2M þ K]þ.
2.1.2. 5,6-Bis(2,6-diisopropylphenoxy)pyrazine-
2,3-dicarbonitrile (4)
2,6-Diisopropylphenol (446 mg, 2.5 mmol) was stirred for 15 min
in an aqueous solution of sodium hydroxide (c ¼ 1 mol dmꢁ3, 2.4 mL,
2.4 mmol,). Compound 1 (200 mg,1 mmol) inTHF (15 mL) was added
dropwise and the mixture stirred for 30 min at room temperature.
The crude product was concentrated to dryness and the brownish-
yellow solid washed thoroughly with water (200 mL) and purified
using column chromatography on silica with toluene/hexane 1:1,
providing awhite solid (404 mg, 83%, mp 208.5e209.5 ꢂC (methanol),
lit. [22] 253 ꢂC (n-hexane)). 1H NMR (300 MHz, CDCl3, 25 ꢂC):
d
¼ 7.39e7.24 (m, 6H, aromH), 2.82 (sept, 4 H, J ¼ 7 Hz, CH),1.23 ppm
(d, 24H, J ¼ 7 Hz, CH3). 13C NMR (75 MHz, CDCl3, 25 ꢂC):
d
¼ 23.2, 28.0,
2.1.6. 2,3,9,10,16,17,23,24-Octakis(octyloxy)-1,4,8,11,15,18,22,25-
(octaaza)phthalocyanine zinc (II) (7)
112.6, 124.2, 124.6, 127.6, 139.8, 146.3, 151.1 ppm. IR (KBr):
nmax ¼ 3068, 3032, 2967, 2930, 2871, 2360, 2344, 2237, 1545, 1460,
1441, 1403, 1385, 1357, 1331, 1258, 1233, 1142, 1112, 1089, 1062, 937,
849, 793 and 750 cmꢁ1. Elemental analysis calc. (%) for C30H34N4O2: C,
74.66, H, 7.10, N, 11.61; found: C, 74.40; H, 7.31; N, 11.99.
ZnQ2Cl2 (153 mg, 0.39 mmol) was transferred to a round bottom
flask, 3 (150 mg, 0.39 mmol) was added and the mixture heated at
190 ꢂC for 60 min. The crude product was dissolved in chloroform
(100 mL), filtered and the solvent removed under reduced pressure.
The solid was then washed with water/methanol 1:1 (300 mL),
adsorbed on silica and thoroughly washed with methanol (300 mL)
on a glass frit. The product was purified using column chroma-
tography on silica with chloroform as eluent. The pure product was
dissolved in chloroform (1 mL), added dropwise to methanol
(50 mL) and the precipitate collected, giving a blue-green solid
(31 mg, 20%). 1H NMR (300 MHz, CDCl3/C5D5N, 25 ꢂC):
2.1.3. 5,6-Bis(4-(hydroxymethyl)phenoxy)pyrazine-
2,3-dicarbonitrile (5)
Compound 1 (400 mg, 2 mmol) was dissolved in THF (10 mL)
and then 4-(hydroxymethyl)phenol (1.24 g, 10.0 mmol) and pyri-
dine (695 mg, 8.8 mmol) were added. After 24 h of stirring at room
temperature the solvent was evaporated and the resulting yellow
oil was dissolved in chloroform (150 mL) and extracted three times
with brine (3 ꢀ 100 mL). The organic layer was dried over anhy-
drous Na2SO4. The crude product was purified by column chro-
matography on silica with ethylacetate/hexane 5:2 and
recrystallized from EtOH/H2O, yielding a white solid (486 mg, 65%,
d
¼ 0.50e0.58 (m, 24 H, CH3), 0.68e1.21 (m, 64 H, CH2), 1.22e1.45
(m, 16H, CH2), 1.59e1.91 (m, 16H, CH2), 4.28e4.85 ppm (m, 16 H,
OCH2). 13C NMR (75 MHz, CDCl3/C5D5N, 25 ꢂC):
d
¼ 13.20, 21.79,
25.53, 28.21, 28.54, 28.80, 31.03, 67.49, 139.48, 147.31 and
151.45 ppm. IR (ATR): nmax ¼ 2954, 2921, 2853, 1638, 1541, 1444,
1377, 1303, 1252, 1121, 1062, 960 cmꢁ1. UV/Vis (pyridine): lmax
m.p. 150.1e152.5 ꢂC). 1H NMR (300 MHz, (CD3)2CO, 25 ꢂC):
d
¼ 4.33
(t, 2 H, J ¼ 5.8 Hz, OH), 4.69 (d, 4H, J ¼ 5.8 Hz, CH2) 7.31 ppm (d, 4H,
(3
) ¼ 624 (199 700), 599 sh (31 500), 568 (28 400), 369 nm
J ¼ 8.6 Hz, aromH). 13C NMR (75 MHz, (CD3)2CO, 25 ꢂC):
d
¼ 64.0,
(134 300 dm3 molꢁ1 cmꢁ1). MS (MALDI-TOF): m/z 1609 [M]þ,

V. Novakova et al. / Dyes and Pigments 87 (2010) 173e179
175
1632 [M þ Na]þ, 1648 [M þ K]þ. Elemental analysis calc. (%) for
C88H136N16O8Znþ4H2O: C, 62.78; H, 8.62; N, 13.31; found: C, 62.80;
H, 8.90; N, 13.21.
A side product with lower Rf was isolated from column chro-
matography. MS (MALDI-TOF): m/z 1497 [M ꢁ C8H16]þ, 1520
[M ꢁ C8H16 þ Na]þ, 1539 [M ꢁ C8H16 þ K]þ, 1385 [M ꢁ 2 ꢀ C8H16]þ.
in the Q-band area was approximately 0.05, excitation wave-
length 368 nm (for 6, 7 and 9) and at 375 nm (for 8). The ZnPc
standard was excited at both wavelengths and corresponding
areas under the curve were used for calculations. Excitation
spectra were collected by observing emission at 680 nm (6 and 7),
690 nm (8) or 700 nm (9). All measurements were performed
three times and the presented data represent mean of these three
experiments.
2.1.7. 2,3,9,10,16,17,23,24-Octakis(2,6-diisopropylphenoxy)-
1,4,8,11,15,18,22,25-(octaaza)phthalocyanine zinc (II) (8)
ZnQ2Cl2 (246 mg, 0.6 mmol) and 4 (300 mg, 0.6 mmol) were
thoroughly mixed and heated at 260 ꢂC employing a condenser for
90 min. The product was washed thoroughly with methanol/water
1:1 (400 mL) and purified using column chromatography on silica
with toluene/chloroform/THF/pyridine 15:15:1:1 as eluent, giving
a green solid (85 mg, 27%), m.p. over 400 ꢂC (slow decomp. from
3. Results and discussion
3.1. Synthesis of substituted pyrazine-2,3-dicarbonitriles
The TPyPz macrocycle is built up by cyclotetramerization of
appropriately substituted pyrazine-2,3-dicarbonitriles. Alkyloxy-
and aryloxy- substituted pyrazine-2,3-dicarbonitriles are easily
accessible by nucleophilic substitutions of 5,6-dichloropyrazine-
2,3-dicarbonitrile (1)[28,31]. Thus, 3 was synthesized in 51% yield
from 1 in anhydrous octanol with triethylamine as acceptor of
released HCl (Fig. 1). A similar synthesis of 2 was reported to have
a yield of 49% [26].
Strictly anhydrous conditions for the preparation of the aryloxy
derivatives [20] seem to be unnecessary as the phenolate anion can
be produced even in aqueous solution. The published procedure
(anhydrous THF, K2CO3, reflux, 24 h) was repeated and compound 4
was synthesized with the yield of 60%. However, the reaction gave
higher yields (83%) when aqueous NaOH (THF, rt, 5 min) was used
to produce phenolate anion. Moreover, it proceeded immediately
after mixing the reactants. Changing solvent to DMF (aqueous
NaOH, rt, 5 min) led to lower yields (41%) and side products were
detected on TLC examination of the mixture.
The above-mentioned procedure (aqueous NaOH, THF) also gave
a reasonable yield (48%) for compound 5 bearing both aromatic and
aliphatic hydroxyls. Lower yields compared to 4 can be most likely
ascribed to side reaction involving attack of 1 by aliphatic hydroxyl as
the nucleophile. Similar competition between aliphatic hydroxyl and
phenolate anion was observed when ethanol was added into the
reaction in order to support solubilization of 4-(hydroxymethyl)
phenol. In this case, yield of 5 decreased to 23% and 5,6-bis(ethoxy)
pyrazine-2,3-dicarbonitrile was isolated from the reaction as the
main product (41%). As a consequence of the aforementioned
nucleophilic substitutionprocess we changed the reaction conditions
and optimized the yield of 5 using pyridine as the base to 65%.
Although the reaction proceeded much slower (24 h), amounts of
side products substantially decreased.
340 ꢂC). 1H NMR (300 MHz, CDCl3, 25 ꢂC):
d
¼ 7.58 (t, 8H, J ¼ 7 Hz,
aromH), 7.45 (d, 16H, J ¼ 8 Hz, aromH), 3.32 (sept, 16H, J ¼ 7 Hz, CH),
1.30 ppm (d, 96H, J ¼ 7 Hz, CH3). 13C NMR (75 MHz; CDCl3, 25 ꢂC):
d
¼ 23.5, 28.1, 124.4,126.6, 141.0, 142.4, 147.9, 149.7 and 151.5 ppm. IR
(KBr): nmax ¼ 3065, 1965, 2931, 2870, 1541, 1401, 1294, 1249, 1213,
1161,1145,1094,1059 and 929 cmꢁ1. UV/Vis (pyridine): lmax
(3) ¼ 628
(200 200), 571 (27 700), 372 nm (117 600 dm3 molꢁ1 cmꢁ1). MS
(MALDI-TOF): m/z 1994 [M þ H]þ. Elemental analysis calc. (%) for
C120H136N16O8Znþ5H2O: C, 68.50; H, 7.09; N, 10.65; found: C, 68.55;
H, 6.13; N, 10.78.
2.1.8. 2,3,9,10,16,17,23,24-Octakis(4-(hydroxymethyl)phenoxy)-
1,4,8,11,15,18,22,25-(octaaza)phthalocyanine zinc (II) (9)
ZnQ2Cl2 (74 mg, 0.18 mmol) and 5 (70 mg, 0.18 mmol) were
mixed, transferred to a round bottom flask and heated at 180 ꢂC for
5 min. The crude product was washed thoroughly with methanol/
water 1:1 (200 mL) and then with common organic solvents (THF,
chloroform, toluene and acetone) (usually 150 mL). The product
was dissolved in pyridine (1 mL) and dropped in to chloroform
(30 mL). The ensuing precipitate was collected, yielding a blue solid
(35 mg, 44%). Solubility of 9 was not sufficient for NMR analysis. IR
(ATR): nmax ¼ 3335, 2931, 2864, 1735, 1670, 1655, 1648, 1604, 1578,
1570, 1541, 1528, 1500, 1388, 1382, 1218, 1158, 1106, 1055, 1013, 924,
817 and 745 cmꢁ1. UV/Vis (pyridine): lmax
(
3
) ¼ 633 (49 100), 579
(12 600), 372 nm (50 000 dm3 molꢁ1 cmꢁ1). Elemental analysis
calc. (%) for C80H56N16O16Zn þ 2H2O: C, 60.10; H, 3.78; N, 14.02;
found: C, 59.64; H, 3.61; N, 14.43.
2.2. Evaluation of the thermal cyclotetramerization
reaction of 4 with ZnQ2Cl2
Compound 4 (48 mg, 0.1 mmol) and ZnQ2Cl2 (41 mg, 0.1 mmol)
were mixed together, transferred to a round bottom flask and
heated at different temperatures for various durations. Afterwards
the product was washed with methanol/water 1:1 (100 mL), dried
and dissolved in chloroform (5.0 mL). The ensuing solution was
diluted 500 times and absorption spectrum was measured. Prog-
ress of the reaction was monitored at 627 nm (maximum of the
Q-band of 8).
3.2. Cyclotetramerization
As previously mentioned the synthesis of alkyloxy- and aryloxy-
substituted TPyPz is not an easy task. Carbons at positions 5 and 6
of the pyrazine ring are strongly electron deficient. As a result they
are usually attacked by alkoxides used as initiators of cyclo-
tetramerization reaction leading to transetherification [28,32]. This
undesirable feature precludes using the common Linstead cyclo-
tetramerization method. Even hindering the reactive centre by
bulky aryloxy substituents did not lead to the successful prepara-
tion of the target TPyPz [20]. The problem of transetherification can
be easily solved for simple aliphatic alkyloxy TPyPz by matching the
metal alkoxide initiator with the appropriate alkyloxy side chain of
the final product. However, this cannot be used for aryloxy deriv-
atives or TPyPz bearing more complicated alkyloxy substituents.
Recently, Makhseed et al. have developed a method for the
cyclisation of various aryloxy TPyPz by heating the corresponding
pyrazine-2,3-dicarbonitriles in quinoline [20,23]. This seemed to be
an effective method for the synthesis of aryloxy TPyPz derivatives.
2.3. Singlet oxygen and fluorescence measurements
Singlet oxygen quantum yields were determined according to
previously published procedure using decomposition of a chem-
ical trap of singlet oxygen 1,3-diphenylisobenzofuran (DPBF)[29].
Absorption of the dyes in the Q-band region during measure-
ments was ca. 0.1. Zinc phthalocyanine (ZnPc) was used as the
reference (FD ¼ 0.61 in pyridine [30]). Fluorescence quantum
yields were determined also by comparative method using ZnPc
as reference (FF ¼ 0.20 in pyridine [30]). Absorption of the dyes

176
V. Novakova et al. / Dyes and Pigments 87 (2010) 173e179
Fig. 1. Synthesis of pyrazine-2,3-dicarbonitriles 2e5. i) TEA, anhydrous R-OH, 75 min, rt (3) or 3 h, reflux (2), ii) ArOH, aq. NaOH, THF, rt, 5 min (4) or pyridine, THF, rt, 24 h (5).
Nonetheless, we were not able to repeat their procedure in the
beginning. Heating of 4 in freshly distilled quinoline by itself or
with anhydrous zinc acetate did not lead to any cyclo-
tetramerization. No absorption in the expected Q-band region in
the UVevis spectrum was detected even after 8 h of heating. A
similar failure was also recently described by other authors [32].
Later, the synthesis of 8 was successfully performed by the
described procedure [20] in another attempt when the conditions
were kept strictly anhydrous and starting materials were carefully
dried. The use of alternative solvents for the synthesis was also
explored. No formation of 8 was detected in dichlorobenzene. A
blue-green product with absorption at expected 628 nm appeared
when DMF or pyridine were used as solvent. However, the reaction
time was quite long (24e30 h) and a number of side products were
detected on TLC examination. In all of the above cases, anhydrous
zinc acetate has been added into the reaction in order to obtain zinc
complexes and to facilitate cyclotetramerization by using the
template effect.
from approx. 340 ꢂC was also observed during melting point
determination. This is in accordance with data from thermogravi-
metric analysis published recently for similar compounds [24]. In
that work, extensive decomposition occurred between 350 and
420 ꢂC. That is why a reaction temperature of 260 ꢂC may be
considered as optimal for 8. Similar analyses of reaction conditions
were performed also for the other three TPyPz 6, 7 and 9 (Fig. 3).
Care was taken particularly on determination of the optimal reac-
tion temperature. Low temperatures did not allow cyclo-
tetramerization, while decomposition occurred at temperatures
above the optimal range. Yields of all the zinc complexes were in
the range 14e44%. When compared to the method of Makhseed
et al.[20], the yields of the ZnQ2Cl2 method were lower but the
reaction did not require strictly anhydrous conditions and the
reaction times were significantly shorter.
The best results from the alternative methods were obtained
employing the route developed by Mørkved et al. with the new
efficient cyclisation agent ZnQ2Cl2 [21,27]. In this case, compound 4
was heated in a melt with ZnQ2Cl2. Different reaction times and
temperatures were used and the progress of the reaction was
monitored using absorbance of the product 8 in its Q-band region
(Fig. 2). The reaction was relatively slow at 220 ꢂC and therefore the
temperature was increased to 260 ꢂC or 350 ꢂC. Heating at the latter
temperature led to the appearance of significant amounts of side
products as detected on TLC examination. Most likely the thermal
stability of the whole macrocycle or the peripheral chains (see also
below) was exceeded at this high temperature. The decomposition
Fig. 2. Progress of cyclotetramerization of 4 in a melt with ZnQ2Cl2 observed as
increasing absorption of 8 at 627 nm (C) 220 ꢂC, (,) 260 ꢂC, (:) 350 ꢂC.
Fig. 3. Synthesis of TPyPz 6e9. i) ZnQ2Cl2, 190 ꢂC, 60 min (6, 7), 260 ꢂC, 90 min (8),
180 ꢂC, 5 min (9).

V. Novakova et al. / Dyes and Pigments 87 (2010) 173e179
177
Table 1
An effort has also been made to reveal the nature of the
decomposition. In the case of 7, the main side product (lower Rf)
was isolated by column chromatography and analyzed by MALDI-
TOF mass spectrometry. The mass spectrum of the isolated fraction
contained mainly a cluster at m/z 1496.8 and a small cluster at m/z
Spectra, photophysical and photochemical properties of studied TPyPz in pyridine.
Compound
Absorbance lmax (nm)/
3
Fluorescence
lmax (nm)
FD
FF
(ꢀ10ꢁ5 dm3 molꢁ1 cmꢁ1
)
6
7
8
9
624/1.89
624/2.00
628/2.00
633/0.49
631
631
637
639
0.54
0.49
0.61
0.18a
0.31
0.30
1384.7 corresponding to stepwise loss of peripheral C8H16 (Dm/z
0.29
112). Compound 7 had a cluster at m/z 1609.0 [M]þ and it was not
detected in this side product. Subsequently, a sample of the side
product was reacted with acetylchloride in anhydrous THF in the
presence of triethylamine. More components with a higher Rf were
detected on TLC suggestive of esterification of the free hydroxyl
groups. An assumption from this experiment can be made, that
higher temperature of the cyclotetramerization reaction induced
thermal cleavage of the ether bond leaving a free OH group on the
macrocycle. Therefore, cyclotetramerization in a melt with ZnQ2Cl2
can be considered as the effective approach to zinc TPyPz bearing
substituents connected through oxygen linkage but care must be
taken to establish optimal reaction temperature.
0.043a
a
Aggregation.
3.4. Fluorescence and singlet oxygen quantum yields
The singlet oxygen production of 6e9 was evaluated quantita-
tively by determination of singlet oxygen quantum yields (FD) in
pyridine (Table 1). The decomposition of a chemical trap e 1,3-
diphenylisobenzofuran (DPBF) e was used for the measurements.
No changes in the absorption spectra were observed during
measurements suggesting that photodegradation did not occur.
Compounds 6e8 showed reasonably high FD values in the range
0.49e0.61 suggesting that oxygen substituted ZnTPyPz may find
their place in applications based on singlet oxygen production, e.g.
as photosensitizers in photodynamic therapy (PDT). The very low
FD of 9 was most likely caused by aggregation as detected in
UVevis absorption spectra. Aggregated TPyPz usually fail in effi-
cient photosensitization because absorbed energy is released
mostly through the heat.
3.3. UVevis absorption
Compounds 6e9 showed a shape of absorption spectra typical
for TPyPz and other porphyrazines. A low energy Q-band was found
at approx. 630 nm and a high energy B-band was found at 370 nm
(see Fig. 4, Table 1). Compounds 6e8 were fully monomeric in
pyridine, but the broader Q-band of 9 indicated partially aggregated
form.
Determined fluorescence quantum yields (FF) followed the
observations made for singlet oxygen. High FF values approx. 0.30
were observed for non-aggregated 6e8 and several times lower FF
was obtained for 9. High FF values are advantageous in PDT
application as well because fluorescence allows simple detection of
photosensitizer accumulation in targeted tissue.
Fluorescence emission spectra of 6e8 had shape typical for
TPyPz and other porphyrazines with only small Stokes shift of
approx. 6 nm (Fig. 5, Table 1). Emission maximum of 8 and 9 was
red-shifted when compared with 6 and 7 due to conjugation of the
aryls with macrocyclic system. The fact that excitation spectra of
6e8 superimposed their absorption spectra (Fig. 6a) confirmed
exclusive presence of the monomeric form during measurements of
fluorescence as well as singlet oxygen generation. On the other
hand, the above-mentioned aggregation of 9 was further confirmed
by different absorption and excitation spectra (Fig. 6b). Aggregates
usually do not fluoresce with the few exceptions of J-dimers [8] and
that is why excitation spectrum corresponds to monomeric form
only.
The position of the Q-band is given mostly by the size of the
-conjugated system of macrocyclic core. The connecting hetero-
p
atom and the electronic character of the peripheral substituent play
a less important but still evident role. Aryloxy- and alkyloxy-
substituted Pc usually show small bathochromic shift of the Q-band
in the range of 5e10 nm when compared with the unsubstituted
derivatives [33]. Contrary to Pc, an oxygen linkage at ZnTPyPz
caused hypsochromic shift when compared to the unsubstituted
macrocycle (unsubstituted ZnTPyPz absorbs at 636 nm in pyridine
[10]). Q-band maxima of 6 and 7 were found at 624 nm in pyridine.
On the other hand, the aryls of 8 and 9 extended the conjugated
system and red-shifted the absorption spectra when compared to
alkyloxy derivatives (628 nm for 8, 633 nm for 9). These observa-
tions are in accordance with data published recently by Mørkved
et al. for pyridin-3-yloxy substituted ZnTPyPz (630 nm in pyridine).
[21] The smaller bathochromic shift of 8 can be attributed to
a lower degree of the aryl conjugation with the macrocyclic system.
The reason is that the bulky isopropyl groups in ortho positions on
the phenoxy substituent cause rotation of the whole 2,6-diisopro-
pylphenoxy group out of the plane of TPyPz
p macrocycle. This fact
has been recently confirmed by crystal structure analysis [34].
Fig. 5. Normalized emission spectra of 6 (dotted), 7 (dashed-dotted, overlaps with 6),
8 (full) and 9 (dashed) in pyridine.
Fig. 4. Normalized absorption spectra of 6 (full line) and 8 (dashed line) in pyridine.

178
V. Novakova et al. / Dyes and Pigments 87 (2010) 173e179
Fig. 6. Normalized absorption (full lines) and excitation (dashed lines) spectra of 6 (a) and 9 (b) in pyridine. Note significant broadening of absorption spectrum of 9 indicating
aggregation.
quantum yields than the corresponding monomers. European Journal of
Organic Chemistry 2008;2008:3260e3.
4. Conclusion
[9] Mørkved EH, Afseth NK, Zimcik P. Azaphthalocyanines with extended
The cyclotetramerization of pyrazine-2,3-dicarbonitriles in
a melt with Zn(quinoline)2Cl2 reagent can be used as a suitable
method for preparation of aryloxy as well as alkyloxy substituted
ZnTPyPz. The procedure does not require strictly anhydrous
conditions. The photophysical and photochemical data were
obtained and suggested that both aryloxy and alkyloxy ZnTPyPz
may be used as photoactive compounds in applications connected
with singlet oxygen production. One drawback is the relatively low
wavelength of absorption. On the other hand, strong fluorescence
in wavelengths optimally suited for human eyes may indicate high
potential in photodetection. No significant differences in FF or FD
values between aryloxy and alkyloxy ZnTPyPz were observed. In
absorption spectra, conjugation of the peripheral aryloxy substit-
uents with the macrocyclic system induced small red shift
(4e9 nm) compared to the alkyloxy derivatives.
conjugation through heteroaryl and aryl substituents. Photochemical and
photophysical properties. Journal of Porphyrins and Phthalocyanines 2007;
11:130e8.
[10] Mørkved EH, Andreassen T, Novakova V, Zimcik P. Zinc azaphthalocyanines
with thiophen-2-yl, 5-methylthiophen-2-yl and pyridin-3-yl peripheral
substituents: additive substituent contributions to singlet oxygen production.
Dyes and Pigments 2009;82:276e85.
[11] Maree MD, Kuznetsova N, Nyokong T. Silicon octaphenoxyphthalocyanines:
photostability and singlet oxygen quantum yields. Journal of Photochemistry
and Photobiology A: Chemistry 2001;140:117e25.
[12] Erdogmus A, Nyokong T. New soluble methylendioxy-phenoxy-substituted
zinc phthalocyanine derivatives: synthesis, photophysical and photochemical
studies. Polyhedron 2009;28:2855e62.
[13] Modibane DK, Nyokong T. Synthesis, photophysical and photochemical
properties of octa-substituted antimony phthalocyanines. Polyhedron 2009;
28:479e84.
[14] Tau P, Nyokong T. Electrocatalytic oxidation of nitrite by tetra-substituted
oxotitanium(IV) phthalocyanines adsorbed or polymerised on glassy carbon
electrode. Journal of Electroanalytical Chemistry 2007;611:10e8.
[15] Durmus M, Nyokong T. Synthesis and solvent effects on the electronic
absorption and fluorescence spectral properties of substituted zinc phthalo-
cyanines. Polyhedron 2007;26:2767e76.
[16] Huang X, Zhao FQ, Li ZY, Tang YW, Zhang FS, Tung CH. Self-assembled
nanowire networks of aryloxy zinc phthalocyanines based on ZneO coordi-
nation. Langmuir 2007;23:5167e72.
Acknowledgement
The work was supported by Research project MSM 0021620822.
ꢁ
ꢁ
[17] Shankar R, Jha NK, Vasudevan P. Synthesis of soluble phthalocyanines and
study of their aggregation behavior in solution. Indian Journal of Chemistry
Section A: Inorganic, Bio-inorganic, Physical, Theoretical and Analytical
Chemistry 1993;32:1029e33.
Authors would like to thank to Jirí Kunes for performing NMR
ꢁ
measurements, to Juraj Lenco for MALDI-TOF measurements and to
Filip Zemek for reading the manuscript.
[18] Idowu M, Nyokong T. Synthesis, photophysics and photochemistry of tin(IV)
phthalocyanine derivatives. Journal of Photochemistry and Photobiology A:
Chemistry 2008;199:282e90.
References
[19] Durmus M, Nyokong T. Synthesis, photophysical and photochemical proper-
ties of aryloxy tetra-substituted gallium and indium phthalocyanine deriva-
tives. Tetrahedron 2007;63:1385e94.
[1] McKeown NB. Phthalocyanine materials: synthesis, structure and function.
Cambridge: Cambridge University Press; 1998.
[2] Kadish KM, Smith KM, Guilard R, editors. The Porphyrin Handbook, vols. 17
and 19. New York: Academic Press; 2003.
[3] Zimcik P, Miletin M, Musil Z, Kopecky K, Kubza L, Brault D. Cationic azaph-
[20] Makhseed S, Ibrahim F, Bezzu CG, McKeown NB. The synthesis of metal-free
octaazaphthalocyanine derivatives containing bulky phenoxy substituents to
prevent self-association. Tetrahedron Letters 2007;48:7358e61.
[21] Mørkved EH, Andreassen T, Bruheim P. Zinc azaphthalocyanines with pyridin-
3-yloxy peripheral substituents. Polyhedron 2009;28:2635e40.
[22] Makhseed S, Samuel J, Ibrahim F. Synthesis and characterization of non-
aggregating octa-substituted azaphthalocyanines bearing bulky phenoxy
substituents. Tetrahedron 2008;64:8871e7.
[23] Makhseed S, Samuel J. The synthesis and characterization of zincph-
thalocyanines bearing functionalized bulky phenoxy substituents. Dyes and
Pigments 2009;82:1e5.
[24] Ibrahim F, Makhseed S. Synthesis and spectral properties of tetrapyr-
azinoporphyrazinato metal complexes derived from a sterically hindered
phenol. Arkivoc; 2008:85e94.
thalocyanines bearing aliphatic tertiary amino substituents
e synthesis,
singlet oxygen production and spectroscopic studies. Journal of Photochem-
istry and Photobiology A: Chemistry 2006;183:59e69.
[4] Tomachinskaya LA, Tret’yakova IN. Effect of styryl substituent introduced into
the periphery of pyrazinoporphyrazine macrocycle on the spectral and
luminescence properties of complexes. Theoretical and Experimental Chem-
istry 2007;43:125e30.
[5] Villano M, Amendola V, Sandona G, Donzello MP, Ercolani C, Meneghetti M.
Excited state dynamics and nonlinear absorption of a pyrazinoporphyrazine
macrocycle carrying externally appended pyridine rings. Journal of Physical
Chemistry B 2006;110:24354e60.
[6] Shishkin VN, Kudrik EV, Makarov SV, Shaposhnikov GP. Cobalt 4-octasulfo-
phenyltetrapyrazinoporphyrazine as a catalyst for the oxidation of organic
substrates with atmospheric oxygen. Kinetics and Catalysis 2007;48:660e3.
[7] Zimcik P, Miletin M, Novakova V, Kopecky K, Nejedla M, Stara V, et al. Effective
monofunctional azaphthalocyanine photosensitizers for photodynamic
therapy. Australian Journal of Chemistry 2009;62:425e33.
[25] Mørkved EH, Holmaas LT, Kjøsen H, Hvistendahl G. Preparation of magnesium
azaphthalocyanines by cyclotetramerisation of S-substituted 4,5-disul-
fanylpyrazine-2,3-dicarbonitriles. Acta Chemica Scandinavica 1996;50:
1153e6.
[26] Zimcik P, Miletin M, Kostka M, Schwarz J, Musil Z, Kopecky K. Synthesis and
comparison of photodynamic activity of alkylheteroatom substituted azaph-
thalocyanines. Journal of Photochemistry and Photobiology A: Chemistry
2004;163:21e8.
ꢁ
[8] Novakova V, Zimcik P, Kopecky K, Miletin M, Kunes J, Lang K. Self-assembled
azaphthalocyanine dimers with higher fluorescence and singlet oxygen

V. Novakova et al. / Dyes and Pigments 87 (2010) 173e179
179
[27] Mørkved EH, Afseth NK, Kjøsen H. Zn(quinoline)2Cl2: an efficient reagent for
synthesis of zinc azaphthalocyanines with thiomorpholine- or pyrazole
substituents. Journal of Porphyrins and Phthalocyanines 2006;10:1301e8.
[28] Mørkved EH, Ossletten H, Kjøsen H. Preparation of octa(alkoxy) azaph-
thalocyanines. Acta Chemica Scandinavica 1999;53:1117e21.
[29] Musil Z, Zimcik P, Miletin M, Kopecky K, Link M, Petrik P, et al. Synthesis and
singlet oxygen production of azaphthalocyanines bearing functional derivatives
of carboxylic acid. Journal of Porphyrins and Phthalocyanines 2006;10:122e31.
[30] Ogunsipe A, Maree D, Nyokong T. Solvent effects on the photochemical and
fluorescence properties of zinc phthalocyanine derivatives. Journal of
Molecular Structure 2003;650:131e40.
Barnyardgrass (Echinochloa crus-galli). Agricultural and Biological Chemistry
1983;47:2923e4.
[32] Uslu Kobak RZ, Öztürk ES, Koca A, Gül A. The synthesis and cyclo-
tetramerisation reactions of aryloxy-, arylalkyloxy-substituted pyrazine-2,3-
dicarbonitriles and spectroelectrochemical properties of octakis(hexyloxy)-
pyrazinoporphyrazine. Dyes and Pigments 2010;86:115e22.
[33] Kobayashi N, Ogata H, Nonaka N, Luk’yanets EA. Effect of peripheral substi-
tution on the electronic absorption and fluorescence spectra of metal-free and
zinc phthalocyanines. Chemistry e A European Journal 2003;9:5123e34.
[34] Makhseed S, Ibrahim F, Samuel J, Helliwell M, Warren JE, Bezzu CG, et al.
Clathrate formation from octaazaphthalocyanines possessing bulky phenoxyl
substituents: a new cubic crystal containing solvent-filled, nanoscale voids.
Chemistry e A European Journal 2008;14:4810e5.
[31] Nakamura A, Ikeda O, Segawa H, Takeuchi Y, Takematsu T. Structureeactivity
relationship in herbicidal activity of 5-Chloro-2,3-dicyanopyrazines against