1,4,8,11,15,18,22,25-octafluorophthalocyaninato zinc (F8PcZn)

Article abstract of DOI:10.1055/s-0031-1290462

1,4,8,11,15,18,22,25-Octafluorophthalocyanato zinc (F₈PcZn), which is not described in the literature up to date, was obtained from 3,6-difluorophthalonitrile in anhydrous DMF, DBU, and Zn(OAc)₂ at 145°C. 3,6-Difluorophthalonitrile w

Full text of DOI:10.1055/s-0031-1290462

LETTER
▌2501
letter
1,4,8,11,15,18,22,25-Octafluorophthalocyaninato Zinc (F8PcZn)
1,4,8,11,15,18,22,25-Octafluorophthalocyaninato Zinc
Göran Crucius,a Alexey Lyubimtsev,b Markus Kramer,a Michael Hanack,*a Thomas Ziegler*a
a
Institut für Organische Chemie, Universität Tübingen, Auf der Morgenstelle 18, 72076 Tübingen, Germany
Fax +49(7071)295244; E-mail: hanack@uni-tuebingen.de; E-mail: thomas.ziegler@uni-tuebingen.de
b
Ivanovo State University of Chemistry and Technology, Organic Chemistry Department, F. Engels Str. 7, 153460 Ivanovo, Russia
Received: 16.07.2012; Accepted after revision: 20.08.2012
1,3,8,10,15,17,22,24-octafluoro metal phthalocyanines
(M = Cu, Co, Ni, Zn) a different multistep procedure was
applied:13 3,5-Dinitrophthalic acid was reacted with urea
and the corresponding metal salts in nitrobenzene. Reduc-
tion of the formed metal octanitrophthalocyanines gave
the corresponding octaamino phthalocyanines. Diazotiza-
tion and reaction with NaBF4 yielded the metal octafluoro-
phthalocyanines.
Abstract: 1,4,8,11,15,18,22,25-Octafluorophthalocyanato
zinc
(F8PcZn), which is not described in the literature up to date, was ob-
tained from 3,6-difluorophthalonitrile in anhydrous DMF, DBU,
and Zn(OAc)2 at 145 °C. 3,6-Difluorophthalonitrile was synthe-
sized by a multistep procedure.
Key words: 1,4,8,11,15,18,22,25-octafluorophthalocyanato zinc,
glycosylated phthalocyanines, fluorinated phthalocyanines,
3,6-difluorophthalonitrile, phthalocyanato metals
Quantum chemical calculations and UPS measurements
on nonsubstituted and a variety of fluorinated metal
phthalocyanines revealed the specific influence of fluo-
rine substitution on the Pc macrocycle: HOMO and
LUMO energy levels are shifted to lower energy, for ex-
ample, in the series PcM > F4PcM > F8PcM > F16PcM
(M = Cu, Zn).13–15
Phthalocyanines (Pc), especially phthalocyanato metals
(PcM), received a lot of attention as dye pigments for var-
ious industrial applications.1 In addition PcM are also
used, for example, as optical limiters,2 photocatalysts,3
and semiconductors4 in the field of material science and
for medical applications like photodynamic therapy
(PDT).5 The chemical stability of the PcM and the oppor-
tunity to control their optical properties via the central
metal atoms and the substitution pattern of the Pc macro-
cycle contributes to the importance and broad applications
of PcM.
Here we report the synthesis and full characterization of
1,4,8,11,15,18,22,25-octafluorophthalocyanoto zinc (8),
which has not been obtained in pure form yet. The synthe-
sis of 8 was carried out as follows (Scheme 1).
F
O
F
O
F
O
With regard to PDT, glycosylated phthalocyanines turned
out to be attractive candidates for in vitro cell tests.6 Pre-
viously, we could show that fluorinated phthalonitriles are
suitable starting materials for the preparation of peri-
pherally glycosylated phthalocyanines.7 Perfluorophthalo-
cyanines (F16PcM) containing a variety of central metals,
for example, Cu, Zn, and Fe are well known.8 The synthe-
sis of F16PcM follows the commonly applied route for the
preparation of metal phthalocyanines, that is, reacting
4-fluorophthalonitrile with a metal salt, for example,
Zn(OAc)2 under basic reaction conditions. Perfluorometal
phthalocyanines have also been studied in detail with re-
gard to their physical properties9 and application in
PDT.10 Polysubstituted phthalocyanines, some of which
are inaccessible by other means, can be prepared by
nucleophilic substitution reactions of F16PcZn with O-, N-,
C-, and S-nucleophiles.11
NEt2
COOH
NEt2
Cl
F
F
F
2
3
1
F
F
F
O
F
F
O
O
NH2
NH2
NH
O
O
O
F
F
O
5
4
6
F
N
Zn
N
F
F
F
F
F
F
So far, isomeric mixtures of tetrafluoro-9a,
2,3,9,10,16,17,23,24-octafluoro-,9a,12 and 1,3,8,10,15,17,
22,24-octafluorophthalocyanies13 containing Cu, Co, Ni,
or Zn as central metal ions have been prepared starting
from 4-fluorophthalonitrile and 4,5-difluorophthalo-
nitrile, respectively, and a metal salt. For the syntheses of
N
N
CN
N
N
N
N
CN
7
F
F
8
SYNLETT 2012, 23, 2501–2503
Advanced online publication: 28.09.2012
DOI: 10.1055/s-0031-1290462; Art ID: ST-2012-B0599-L
© Georg Thieme Verlag Stuttgart · New York
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
Scheme 1 Synthesis of F8PcZn

2502
G. Crucius et al.
LETTER
Commercially available 2,5-difluorobenzoyl chloride (1) 13C NMR spectra of compounds 5–7 in DMSO confirmed
was converted with diethylamine into 2,5-difluoro-N,N- the expected values. Due to the poor solubility of 8 in or-
diethylbenzamide (2) which was subsequently reacted ganic solvents no satisfying 13C spectrum has been ob-
with n-butyllithium, CO2, and water to afford 2-[diethyl- tained. With a negative range starting from –109.3 ppm
amino]carbonyl-3,6-benzoic acid (3).16
for compound 7 up to –120.6 for 5 19F NMR spectra of
compounds 5–8 were recorded in DMSO.
Next, 3,6-difluorophthalic anhydride (4) was obtained by
heating 3 in a mixture of concentrated sulfuric acid and The UV-vis spectrum of F8PcZn (8) in chloroform with a
water under reflux. Anhydride 4 was purified by sublima- sharp Q-band at λ = 690 nm and two small shoulders at λ
tion under reduced pressure.16 Melting 4 with urea forms = 660 nm and 622 nm is shown in Figure 1.
3,6-difluorophthalimide (5), which was transformed into
3,6-difluorophthalic acid amide (6) by treatment with
aqueous ammonia. Next, diamide 6 was reacted with thio-
nyl chloride to give 3,6-difluorophthalonitrile (7). For the
formation of 1,4,8,11,15,18,22,25-octafluorophthalocya-
nato zinc (8) a solution of phthalonitrile 7 in anhydrous
DMF and Zn(OAc)2 was heated with addition of DBU or
hexamethyldisilazane, respectively.
Whereas the synthesis of compounds 1–4 was carried out
under reaction conditions which are described,16 forma-
tion of 5 was somewhat difficult. Reacting the acid anhy-
dride 4 with urea under standard conditions at 200 °C for
several hours resulted in a low yield (<20%). Lowering
the temperature to 125–130 °C for four hours led to a
yield of 83% for compound 5. 3,6-Difluorophthalic acid
Figure 1 UV-vis spectrum of F8ZnPc (8) in chloroform
amide (6) was obtained in 60% yield by treatment of 5
with aqueous ammonia at ambient temperature. Dehydra-
tion of 6 with thionyl chloride in anhydrous DMF at about
0 °C yielded 74% of phthalonitrile 7. Title compound 8
has been received under reaction conditions mentioned
before.
F8PcZn (8) was further characterized using MALDI-TOF
and FT-ICR-MS.
In conclusion, we have prepared and fully characterized
the last structural isomer 8 of octafluorophthalocyanines
F8PcZn. In addition one of the most promising precursors
for glycosylated phthalocyanines, 3,6-difluorophthalo-
nitrile (7), has been synthesized. Detailed experiments for
glycosylated phthalocyanines starting from 7 are in prog-
ress.
Purification of 1,4,8,11,15,18,22,25-octafluorophthalo-
cyaninato zinc (8) was challenging due to the difficult re-
moval of trace impurities. The best purification results
were obtained by using chromatography on silica gel and
aluminum oxide in addition with different solvent mix-
tures to obtain F8PcZn (8) in 29% yield. An analytical
sample was further purified by HPLC using a mixture of
acetonitrile and water on a reverse-phase column. Purity
of 8 was brought up to 96% as determined by LC–MS.
Starting materials and reagents were purchased from ABCR GmbH
(2,5-difluorobenzoyl chloride), Acros Organics (thionyl chloride),
and Sigma-Aldrich (DBU) and were of the highest purity available.
DMF was distilled from phosphorous pentoxide and was stored
over MS 3 Å under an atmosphere of nitrogen until used. NMR
spectra were recorded on a Bruker Avance 400 (1H, 13C) or a Bruker
ARX 400 (19F). Melting points are uncorrected and determined with
a Büchi Melting Point M-560. Elemental analyses were performed
on a HEKAtech Euro EA Analyzer. Coupling constants were calcu-
lated with gNMR (5.1). Maldi-TOF spectra were measured on a
Bruker Daltonics. FT-ICR-MS were recorded on a Bruker Apex II
FT-ICR-MS spectrometer.
Compounds 5–8 were fully characterized using different
spectroscopic techniques. 1H NMR spectra of compounds
5–8 were in accordance with the expected results. The
coupling constants were obtained by performing a full-
lineshape iteration on the AA′ part of the AA′XX′ spin
systems using gNMR 5.1.17 The final values are given in
Table 1.
3,6-Difluorophthalimide (5)
Table 1 Calculated Coupling Constants for Compounds 5, 6, 7, and 8
3,6-Difluorophthalic anhydride (4,16 10.9 g, 60.0 mmol) was in-
tensely mixed with urea (7.6 g, 126.0 mmol) and subsequently fused
at 125–130 °C for 4 h. The resulting hot slurry was poured into cold
H2O (150 mL) as fast as possible. The formed solid was collected
by filtration, washed several times with H2O, and dried in a vacuum
oven (60 °C, 1·10–2 mbar) over night. Recrystallization from tolu-
ene gave imide 5 (9.18 g, 83%) as a light-yellow solid; mp 185–
186 °C. IR (KBr): 3253, 3090, 2696, 1783, 1738, 1258, 1063, 895
cm–1. 1H NMR (400 MHz, DMSO-d6): δ = 7.69 (t, 2 H, 5JF,F = 22.4
Hz, 3JH-4,F-3 = 3JH-5,F-6 = 8.7 Hz, 4JH-4,F-6 = 4JH-5,F-3 = 3.1 Hz, 3JH-4,H-5
= 9.2 Hz, H-4, H-5), 11.58 (s, 1 H, NH). 13C NMR (100.6 MHz,
Compound
3JH,H′ (Hz)
9.2
3JH,F (Hz)
8.7
4JH,F (Hz) 5JF,F (Hz)
5
6
7
8
3.1
3.9
4.0
3.1
22.4
18.6
15.1
22.4
9.6
8.7
9.2
8.8
9.2
8.6
Synlett 2012, 23, 2501–2503
© Georg Thieme Verlag Stuttgart · New York

LETTER
1,4,8,11,15,18,22,25-Octafluorophthalocyaninato Zinc
2503
DMSO-d6): δ = 119.6 (dd, JC,F = 9.9 Hz, JC,F = 6.0 Hz, 2 C), 125.1
(dd, JC,F = 18.3 Hz, JC,F = 13.4 Hz, 2 C), 152.8 (dd, 1JC,F = –259.8
Hz, JC,F = 3.8 Hz, 2 C), 165.1 (s, CO). 19F NMR{1H} (376.5 MHz,
DMSO-d6): δ = –120.46. MS–FAB: m/z (%) = 184 (20) [M + H]+,
124 (18). Anal. Calcd for C8H3F2NO2: C, 52.47; H, 1.65; N, 7.65.
Found: C, 52.13; H, 1.76; N, 7.40.
C32H9F8N8Zn: 721.010841; found: 721.010744; Δ = 0.14 ppm. MS-
Maldi-TOF: m/z [M]+ calcd for C32H8F8N8Zn: 720.004; found:
719.995.
Acknowledgment
3,6-Difluorophthalamide (6)
Financial support of the Deutsche Forschungsgemeinschaft (DFG,
ZI: 338/8-1) is highly acknowledged.
3,6-Difluorophthalimide (5, 5,4 g, 29.4 mmol) and concd NH3 solu-
tion (125 mL, 25% in H2O) were stirred at r.t. for 48 h. The formed
solid was collected by filtration, washed with H2O until the filtrate
was neutral and dried in vaccuo. Recrystallization from EtOH–H2O
(1:1) gave colorless crystals of 6 (3.53 g, 60%); mp 219–221 °C. IR
(KBr): 3336, 3175, 2360, 1689, 1663, 1466, 1409, 915, 633 cm–1.
1H NMR (400 MHz, DMSO-d6): δ = 7.34 (t, 2 H, 5JF,F = 18.6 Hz,
3JH-4,F-3 = 3JH-5,F-6 = 8.7 Hz, 4JH-4,F-6 = 4JH-5,F-3 = 3.9 Hz, 3JH-4,H-5 = 9.6
Hz, H-4, H-5), 7.70 (s, 2 H, NH2), 7.84 (s, 2 H, NH2). 13C NMR
(100.6 MHz, DMSO-d6): δ = 117.6 (dd, JC,F = 20.1 Hz, JC,F = 14.4
Hz, 2 C), 125.8 (dd, JC,F = 16.2 Hz, JC,F = 9.6 Hz, 2 C), 154.2 (dd,
1JC,F = –244.9 Hz, JC,F = 3.6 Hz, 2 C), 163.8 (s, 2 C, CO). 19F
NMR{1H} (376.5 MHz, DMSO-d6): δ = –120.63. MS–FAB: m/z
(%) = 201 (20) [M + H]+. Anal. Calcd for C8H6F2N2O2: C, 48.01; H,
3.02; N, 14.00. Found: C, 47.98; H, 3.17; N, 14.06.
References and Notes
(1) Smith, H. M. In High Performance Pigments, 1st ed.;
Tanaka, M., Ed.; Wiley-VCH: Weinheim, 2002, 263.
(2) (a) Shirk, J. S.; Pong, R. G. S.; Bartoli, F. J.; Snow, A. W.
Appl. Phys. Lett. 1993, 1880. (b) Dini, D.; Barthel, M.;
Hanack, M. Eur. J. Org. Chem. 2001, 3759.
(3) Xu, H.; Chan, W. H.; Ng, D. K. P. Synthesis 2009, 1791.
(4) (a) Petritsch, K.; Dittmer, J. J.; Marseglia, E. A.; Friend, R.
H.; Lux, A.; Rozenberg, G. G.; Roratti, S. C.; Holmes, A. B.
Sol. Energy. Mater. Sol. Cells 2000, 63. (b) Kadish, K. M.;
Smith, K. M.; Guilard, R. In The Porphyrin Handbook; Vol.
17; 1st ed. Dini, D.; Hanack, M. Academic Press: San Diego,
2003, 1.
3,6-Difluorophthalonitrile (7)
(5) Brown, S. G.; Tralau, C. J.; Coleridge Smith, P. D.;
Akdemir, D.; Wieman, T. J. Br. J. Caner 1986, 43.
(6) Soares, A. R. M.; Neves, M. G. P. M. S.; Tomé, A. C.; Cruz,
M. C.; Zamarron, A.; Carrasco, E.; Gonzalez, S.; Cavaleiro,
J. A. S.; Torres, T.; Guldi, D. L.; Juarranz, A. Chem. Res.
Toxicol. 2012, 940.
Anhydrous DMF (70 mL) was cooled to 0 °C with an ice bath be-
fore SOCl2 (3 mL, 41.0 mmol) was added dropwise. The solution
was stirred at 0 °C for an additional hour. While maintaining the in-
ner temperature below 5 °C 3,6-difluorophthalamide (6, 3.90 g,
19.5 mmol) was added in small portions. The reaction mixture was
allowed to warm to r.t. and stirred over night. The reaction mixture
was slowly poured onto crushed ice (200 mL), the formed precipi-
tate was collected by filtration, washed several times with H2O, and
dried over P4O10. Colorless solid (2.37 g, 74%); mp 147–150 °C. IR
(KBr): 3107, 3095, 3076, 2246, 1486, 1263, 927, 848, 735 cm–1. 1H
NMR (400 MHz, DMSO-d6): δ = 8.05 (t, 2 H, 5JF,F = 15.1 Hz, 3JH-
4,F-3 = 3JH-5,F-6 = 8.8 Hz, 4JH-4,F-6 = 4JH-5,F-3 = 4.0 Hz, 3JH-4,H-5 = 9.2 Hz,
(7) Iqbal, Z.; Lyubimtsev, A.; Herrmann, T.; Hanack, M.;
Ziegler, T. Synthesis 2010, 3097.
(8) (a) Hiller, S.; Schlettwein, D.; Armstrong, N. R.; Wöhrle, D.
J. Mater. Chem. 1998, 945. (b) Kol’tsov, E.; Basova, T.;
Semyannikov, P.; Igumenov, I. Mater. Chem. Phys. 2004,
222. (c) Duggan, P. J.; Gordon, P. F. EP 155780, 1985.
(d) Reynolds, S. J.; Gregory, P. EP 787732, 1997.
(9) (a) Brinkmann, H.; Kelting, C.; Makarov, S.; Tsaryova, O.;
Schnurpfeil, G.; Wöhrle, D.; Schlettwein, D. Phys. Status
Solidi A 2008, 409. (b) Gerdes, R.; Lapok, L.; Tsaryova, O.;
Wöhrle, D.; Gorun, S. M. Dalton Trans. 2009, 1098. (c) Liu,
Y.; Yang, D.; Wang, C. J. Phys. Chem. 2006, 20789.
(10) (a) Oda, K.; Ogura, S.; Okura, I. J. Photochem. Photobiol.,
B 2000, 20. (b) Garcia, A. M.; Alarcon, E.; Munoz, M.;
Scaiano, J. C.; Edwards, A. M.; Lissi, E. Photochem.
Photobiol. Sci. 2011, 507.
(11) Leznoff, C. C.; Sosa-Sanchez, J. L. Chem. Commun. 2004,
338.
(12) Murdey, R.; Sato, N.; Bouvet, M. Mol. Cryst. Liq. Cryst.
2006, 211.
(13) Reddy, K. R. V.; Harish, M. N. K.; Fassiulla; Khan, M. H.
M.; Keshavayya, J. J. Fluorine Chem. 2007, 128, 1019.
(14) Hiller, S.; Schlettwein, D.; Armstrong, N. R.; Wöhrle, D.
J. Mater. Chem. 1998, 945.
(15) Liao, M. S.; Watts, J. D.; Huang, M. J.; Gorunn, S. M.; Kar,
T.; Scheiner, S. J. Chem. Theory Comput. 2005, 1201.
(16) Krapcho, A. P.; Getahun, Z.; Avery, K. J. Jr. Synth.
Commun. 1990, 2139.
H-4, H-5). 13C NMR (100.6 MHz, DMSO-d6): δ = 104.2 (dd, JC,F
15.4 Hz, JC,F = 8.3 Hz, 2 C), 110.9 (s, 2 C, CN), 124.5 (dd, JC,F
=
=
18.8 Hz, JC,F = 13.3 Hz, 2 C), 159.1 (dd, 1JC,F = –257.2 Hz, JC,F = 3.4
Hz, 2 C). 19F NMR{1H} (376.5 MHz, DMSO-d6): δ = –109.25. MS–
FAB: m/z (%) = 164.1 (30) [M]+. Anal. Calcd for C8H2F2N2: C,
58.55; H, 1.23; N, 17.07. Found: C, 58.94; H, 1.29; N, 16.84.
1,4,8,11,15,18,22,25-Octafluorophthalocyanato Zinc (8)
A mixture of 3,6-difluorophthalodinitrile (7, 820 mg, 5.0 mmol),
Zn(OAc)2 (710 mg, 3.86 mmol), and DBU (250 μL) in anhydrous
DMF (5 mL) was stirred and heated at 145 °C overnight under a ni-
trogen atmosphere. The cooled solution was poured into MeOH (20
mL) and the greenish blue precipitate was collected by filtration.
The obtained solid was dried and purified on a short pad of silica
gel. The crude product was further purified by column chromatog-
raphy using basic Al2O3 first with CH2Cl2 and EtOAc containing 0–
20% MeOH. The obtained product was absorbed on silica gel and
eluted with PE–EtOAc (2:1), followed by EtOAc containing 0–20%
MeOH to yield a deep-green solid (262 mg, 29%). An analytical
sample was further purified on a reversed-phase HPLC C-18 col-
umn using MeCN and H2O to yield 8 as a green solid; mp >400 °C.
1H NMR (400 MHz, DMSO-d6): δ = 7.71 (t, 8 H, 5JF,F = 22.4 Hz,
3JH-2,F-1 = 3JH-3,F-4 = 8.6 Hz, 4JH-2,F-4 = 4JH-3,F-1 = 3.1 Hz, 3JH-2,H-3 = 9.2
Hz, Hβ-Pc). 19F NMR{1H} (376.5 MHz, DMSO-d6): δ = –120.03.
UV-vis (CHCl3): λmax (log ε) = 690 (7.22), 660 (6.46), 622 (6.48),
368 (6.57). FT-ICR-MS (ESI): m/z [M + H]+ calcd for
(17) NMR simulation program, Licensor Budzelaar, P. H. M.,
marketed by Adept Scientific until May 2005.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2012, 23, 2501–2503

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