Anomerically glycosylated zinc(II) naphthalocyanines

Article abstract of DOI:10.1016/j.tetlet.2009.07.127

In course of our work on sugar-substituted phthalocyanines (Pc's) for PDT applications, for the first time two macrocyclic Pc homologs, the anomerically tetraglucosylated Zn(II) naphthalocyanines 11 and 12 were synthesized and characterized.

Full text of DOI:10.1016/j.tetlet.2009.07.127

Tetrahedron Letters 50 (2009) 5681–5685
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Tetrahedron Letters
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Anomerically glycosylated zinc(II) naphthalocyanines
a,
Zafar Iqbal a, Alexey Lyubimtsev b, Michael Hanack a, , Thomas Ziegler
*
*
a Institut für Organische Chemie, Universität Tübingen, Auf der Morgenstelle 18, 72076 Tübingen, Germany
b Ivanovo State University of Chemistry and Technology, Organic Chemistry Department, F. Engels Str. 7, 153460 Ivanovo, Russia
a r t i c l e i n f o
a b s t r a c t
Article history:
In course of our work on sugar-substituted phthalocyanines (Pc’s) for PDT applications, for the first time
two macrocyclic Pc homologs, the anomerically tetraglucosylated Zn(II) naphthalocyanines 11 and 12
were synthesized and characterized.
Received 2 July 2009
Accepted 22 July 2009
Available online 26 July 2009
Ó 2009 Elsevier Ltd. All rights reserved.
The conjugation of carbohydrates with macrocycles, such as
porphyrins, has been widely considered, mostly for use in photody-
namic therapy (PDT). PDT uses photosensitizers as a source of sin-
glet oxygen. Porphyrin-type compounds (e.g., porphyrins and/or
phthalocyanines) photosensitize the formation of highly reactive
singlet oxygen via transfer of energy from the triplet-excited state
of the porphyrinoid to the triplet-ground state of oxygen. Singlet
oxygen is a potent oxidant that reacts with several functional
groups of biomolecules.1 The drugs used in PDT still possess some
drawbacks such as low chemical selectivity toward the intended
targets and uptake by cells mostly arises from passive or diffusion
processes.2 Because the balance between hydrophobicity and
hydrophilicity is acknowledged as a significant aspect for the de-
sign of new photosensitizers,3,4 diverse research groups have syn-
thesized a variety of new porphyrinoid–carbohydrate conjugates5
assuming that the presence of the carbohydrate moiety could im-
prove the membrane interaction, therefore increasing their tumor
selectivity. Moreover, various types of glucose transporters are
specific for different monosaccharides in cancer cells.6
Phthalocyanine (Pc)–carbohydrate conjugates contrary to por-
phyrin–carbohydrate systems are less common despite their great
potential in PDT. To our knowledge only symmetrical7–10 and
unsymmetrical11,12 phthalocyaninato zinc(II) compounds periph-
erally substituted with four glucose or galactose units and phtha-
locyaninato silicon(IV) complexes axially substituted with two
galactose13 or glucose14 molecules have been reported; however,
in none of these cases the Pc is linked to the carbohydrate through
the anomeric carbon, like in most of the porphyrinoid–carbohy-
drate conjugates.15,16
A drawback of the tetraglycosylated Pc’s which were prepared
by tetramerization of monoglycosylated phthalonitriles, however,
is the fact that these Pc’s are obtained as mixtures of constitutional
isomers which are difficult to separate.18
In order to circumvent the formation of isomers we recently
prepared a symmetrically 4,5-diglycosylated phthalonitrile which
afforded for the first time a constitutional uniform octaglycosylat-
ed Pc.19 As sugar moiety, we chose 1,2:3,4-di-O-isopropylidene-
a-
D
-galactopyranose which was attached to the Pc macrocycle via its
position 6.19
We have also been successful now to obtain anomerically octa-
glycosylated zinc(II) phthalocyanines in which the sugar part is
protected as well as deprotected. The sugars glucose, galactose, lac-
tose, cellobiose and maltose were anomerically attached either via
oxygen or via sulfur to the Pc ring.20
In addition to porphyrins and Pc’s also naphthalocyanines (Nc’s)
have been used as photosensitizers in PDT. Nc’s are of particular
interest due to their absorption maxima in the range of 750–
800 nm, where light penetration through skin and tissues is
approximately twice for that of Pc’sꢀ630 nm.21 This would allow
treatment of larger and more deeply lying tumors.22 Several
peripherally substituted metal naphthalocyanines have been syn-
thesized and studied for their use in PDT by various research
groups.23
We have extended our work on glycoconjugated Pc’s to Nc’s and
report here about the first example of peripherally tetraglucose-
substituted Zn(II) naphthalocyanines 11 and 12 linked via the ano-
meric carbon (Fig. 2).
Our synthesis of the tetraglucose Zn(II) naphthalocyanines in
high yield via template reaction of the glucosylated naphthalodi-
nitrile 5 (Fig. 1) is based on the possibility to obtain glucos-
yloxyphthalonitriles, in high yields by nucleophilic substitution
of 4-nitrophthalonitrile with protected glycopyranoses.24
To synthesize the glucosylated naphthalodinitrile 5 (Fig. 1) the
same SNAr displacement of nitrite in 6-nitronaphthalodinitrile
6a24 by anomerically deprotected glucose 7 in various polar apro-
tic solvents such as DMF, DMSO and HMPA at room temperature,
We reported for the first time a series of peripherally tetragly-
cosylated Pc’s with
D
-glucopyranose, 1-thio-b-
D-glucopyranose, b-
D
-galactopyranose, 1-thio-b-
D
-cello- and lactobiose.17
* Corresponding authors. Tel.: +49 0 7071 29 72432; fax: +49 0 7071 29 5244
(M.H.), tel.: +49 0 7071 29 73035 (T.Z).
E-mail addresses: hanack@uni-tuebingen.de (M. Hanack), thomas.ziegler@uni
-tuebingen.de (T. Ziegler).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.07.127

5682
Z. Iqbal et al. / Tetrahedron Letters 50 (2009) 5681–5685
O
OAc
O
AcO
HO
O
1
AcO
i
+
3
ii
2
O
CHBr2
CHBr2
O
AcO
4
iii
O
CN
CN
O
AcO
5
iv
HO
CN
CN
X
CN
CN
X
6a = NO
6b = F
2
6
8
+
+
O
O
OH
AcO
AcO
7
9
Br
Figure 1. Synthesis of glucosylated naphthalodinitrile 5. Reagents and conditions: (i) 1 + 2, BF3:etherate, benzene, rt, 48 h, 94% 3; (ii) 3, NBS, benzoyl peroxide, CCl4, reflux,
48 h, 91% 4; (iii) 4, fumaronitrile, NaI, DMF, 75–80 °C, 24 h, 65% 5; (iv) 8 + 9, Ag2O, CH3CN, 50 °C, 24 h, 71% 5.
with NaH and K2CO3 as bases was followed. In spite of different
conditions which were applied, no sugar nitrite exchange was ob-
served. Increasing the temperature mostly led to the degradation
of the sugar part. To increase the reactivity of the leaving group X
in the naphthalodinitrile 6, instead of the nitro- the correspond-
ing fluoronaphthalodinitrile 6b was reacted with sugar 7. How-
ever, also the fluoronaphthalodinitrile 6b using different
conditions did not react with the sugar 7 to form the expected
substitution product 5.
A more detailed investigation concerning the reactivity of both
the 6-nitro- and the 6-fluoronaphthalodinitriles 6a, b not only with
the sugar 7 but also, for example, with n-hexanol as the alcohol
part in solvents such as DMF, DMSO and HMPA, respectively, and
K2CO3 or NaH as bases gave no indication for a substitution reac-
tion at room temperature or slightly elevated temperatures. At
higher temperatures (80–100 °C) only degradation products were
found.
than the well investigated reactivity of the 4-substituted
phthalonitriles.
Therefore the synthesis of glucosylated naphthalodinitrile 5
was carried out using the well known route for the preparation
of substituted naphthalodinitriles26 (Fig. 1): first the glucose part
was introduced by a Koenigs–Knorr type glycosidation reaction
of 3,4-dimethylphenol 2 with penta-O-acetyl-b-D-glucose 1 under
activation with BF3–etherate leading to compound 3.27 3 could
be brominated with NBS in CCl4 to form tetrabromide 4 in good
yield28 which was reacted with fumaronitrile and NaI in DMF in
a Diels–Alder process to obtain the glucosylated naphthalodinitrile
5 (Fig. 1).29
Naphthalodinitrile 5 was also obtained by reacting 6-hydroxy
naphthalodinitrile30 (8) with the acetylated bromoglucose 9.29
The sugar part of naphthalodinitrile 5 was deprotected with Na
in methanol while passing gaseous NH3 through the solution to
form the corresponding diiminoisoindoline31 10 which was subse-
quently reacted with Zn(OAc)2ꢁ2H2O in DMAE as solvent, after
which the tetraglucosylated NcZn 12 was obtained as a mixture
of structural isomers.32
Nucleophilic substitution of 6a has only been reported with
sterically hindered phenols.25 Even in these cases the yields of
substitution products are low and side products of unknown
structure are formed. These and our own experiments also dem-
onstrate that the nucleophilic reactivity of the nitro- and fluoro-
substituted naphthalodinitriles 6 is much lower and less clear
Naphthalocyanine 11 was formed by direct tetramerization of
naphthalodinitrile
5 with hexamethyldisilazan, p-TsOH and
Zn(OAc)2ꢁ2H2O in refluxing DMF.33 Treating 11 with CH3ONa in a

Z. Iqbal et al. / Tetrahedron Letters 50 (2009) 5681–5685
5683
O
CN
O
AcO
CN
5
O
O
AcO
i
iii
NH
O
N
N
N
O
HO
O
O
O
N
N
O
Zn
OAc
N
AcO
N
N
N
10
11
NH2
HO
O
O
iv
ii
O
O
OAc
N
N
N
O
O
O
N
N
O
Zn
OH
HO
N
N
N
12
O
O
OH
Figure 2. Synthesis of tetraglucosylated zinc(II) naphthalocyanines. Reagents and conditions: (i) 5, Na, NH3, methanol, rt-reflux, 2 h, 99% 10; (ii) 10, Zn(OAc)2ꢁ2H2O, DBU,
DMAE, reflux, 24 h, 29% 12; (iii) 5, Zn(OAc)2ꢁ2H2O, HMDS, p-TsOH, DMF, reflux, 15 h, 45% 11; (iv) 11, CH3ONa, MeOH, DMSO, rt, 12 h, 93% 12.
DMSO/methanol mixture (2:1) the acetyl groups were removed
and the deprotected NcZn 12 was formed.32
A
2.4
Contrary to the completely water soluble tetraglucose substi-
2.2
tuted PcZn17 the corresponding NcZn 12 is much less soluble in
2.0
water at room temperature, but soluble in DMF, DMSO and hot
1.8
water. The lower solubility of 12 in water is a result of the larger
hydrophobic Nc-macrocycle for which the four hydrophilic substit-
uents are not sufficient enough to allow water solubility. NcZn 11
is soluble in organic solvents such as CHCl3 and THF.
4
1.6
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0.0
3
2
1
In solution both Nc’s 11 and 12 depending upon the solvent are
aggregated. This was directly demonstrated through the UV/Vis
spectra of the acetyl protected tetraglucosylated NcZn 11: Its UV/
Vis spectrum in DCM shows a strong broad band with the maximum
at 696 nm typical for strong aggregation. The Q-band of 11 only ap-
pears as shoulder at 769 nm. Traces of pyridine added to the DCM
solution of 11 led to an interruption of the aggregation shown in
the UV/Vis spectrum by a now strong narrow Q-band with the max-
imum at 763 nm and a broad band of low intensity at 704 nm. In
DMSO as solvent 11 and 12 show less aggregation as shown by
strong Q-bands at 769 and 773 nm, respectively (Fig. 3).
λ. nm
300
400
500
600
700
800
900
1000
Figure 3. UV–vis spectra of NcZn’s 11 and 12. (1) NcZn 11 in DCM
(c = 0.16 ꢂ 10ꢃ7 M). (2) NcZn 11 in DCM with traces of pyridine. (3) NcZn 11 in
DMSO (c = 0.14 ꢂ 10ꢃ7 M). (4) NcZn 12 in DMSO (c = 0.6 ꢂ 10ꢃ7 M).

5684
Z. Iqbal et al. / Tetrahedron Letters 50 (2009) 5681–5685
24. Alvarez-Mico, X.; Calvete, M. J. F.; Hanack, M.; Ziegler, T. Carbohydr. Res. 2007,
The 1H NMR spectra of 11 and 12 were recorded in Methanol-d4
342, 440–447.
and DMSO-d6, respectively. Both NMR spectra depend very much
upon the temperature of the solution which for both compounds
has been increased from 20 to 100 °C. Only at higher temperatures
very well resolved spectra were obtained indicating aggregation of
11 and 12 even in coordinating solvents such as DMSO-d6 and
methanol-d4. In non-coordinating solvents, for example, CDCl3,
the spectra especially in the aromatic region were of very low
intensity. Even the addition of pyridine-d5 did not change the spec-
tra very much at ambient temperature.
25. Brewis, M.; Clarkson, G. J.; Humberstone, P.; Makhseed, S.; McKeown, N. B.
Chem. Eur. J. 1998, 4, 1633–1640.
26. Mikhalenko, S. A.; Luk’yanets, E. A. Zh. Obsch. Khim. 1969, 39, 2554–2558.
27. Sokolov, V. M.; Zakharov, V. I.; Studentsov, E. P. Russian J. General Chemistry
(Translation of Zhurnal Obshchei Khimii) 2002, 72, 806–811; (b) 3,4-
Dimethylphenyl-2,3,4,6-tetra-O-acetyl-
D
-glucopyranoside (3): To
a solution
of (11.71 g, 30 mmol) of penta-O-acetyl-b-
D-glucopyranose (1) and (4 g,
33 mmol.) of 3,4-dimethylphenol (2) in dry benzene (100 mL) was added
boron trifluoride etherate (0.4 mL). The reaction mixture was stirred at room
temperature for 48 h. After completion, the reaction was terminated by
dilution with benzene (100 mL). The benzene solution was washed with water,
sodium hydroxide (1 N), and water to neutral washings, dried with sodium
sulfate and evaporated in vacuo to obtain syrup-like product which was
recrystallized from hot ethanol to get white solid. Yield 12.76 g (94%). Mp:
Work is now in progress to synthesize NcZn’s containing more
than four glucose substituents thereby increasing the hydrophilic-
ity of such Nc-derivatives and making them water soluble.
113–115 °C. ½a 2D0
ꢄ
= ꢃ7.1 (c 1, CHCl3). 1H NMR (400 MHz, CDCl3): d = 7.00 (d,
3J = 8.1 Hz, 1H, H-50), 6.76 (d, J = 2.3 Hz, 1H, H-20), 6.70 (dd, 3J = 8.1 Hz,
J = 2.3 Hz, 1H, H-60), 5.28–5.19 (m, 2H, H-1, H-3), 5.12 (t, 1H, H-2), 5.01 (d,
3J = 7.4 Hz, 1H, H-4), 4.27 (dd, J6a,6b = 12.4, J6a,5 = 5.4, 1H, H-6a), 4.15 (dd,
J6b,6a = 12.4, J5,6b = 2.5, 1H, H-6b), 3.84–3.78 (m, 1H, H-5), 2.20, 2.17 (2s, 6H,
H–CH3), 2.06, 2.03, 2.01, 2.00 (4s, 12H, H(Ac)); 13C NMR (100 MHz, CDCl3):
d = 171.0, 170.6, 169.8, 169.7 (4C, C@O), 155.4 (1C, C10), 138.3 (1C, C-20), 131.9
(1C, C-60), 130.7 (1C, C-50), 118.9 (1C, C-30), 114.4 (1C, C-40), 99.8 (1C, C-1), 73.1
(1C, C-2), 72.3 (1C, C-3), 71.6 (1C, C-5), 68.7 (1C, C-4), 62.4 (1C, C-6), 21.2, 21.0,
20.9, 20.8, 20.3, 10.3 (6C, CH3): FTICR MS m/z 475.15747 [M+Na]+. IR (KBr):
2957, 1755, 1607, 1503, 1429, 1368, 1213, 1169, 1095, 1077, 1045, 908, 817,
Acknowledgment
Z. Iqbal thanks Higher Education Commission (HEC) Pakistan,
for generous grant of PhD scholarship.
References and notes
600 cmꢃ1
28. 3,4-Bis(dibromomethyl)phenyl-2,3,4,6-tetra-O-acetyl-
3,4-dimethylphenyl-2,3,4,6-tetra-O-acetyl- -glucopyranoside 3 (9 g, 20 mmol),
.
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D-glucopyranoside (4):
D
NBS (14.24 g, 80 mmol), and benzoyl peroxide (0.15 g) were stirred in dry CCl4
(100 mL) at reflux for 48 h, while illuminating the mixture with 250 W tungsten
lamp. The warm solution was filtered and the precipitate was washed with warm
CCl4 (50 mL). After removal of bromine traces with NaHSO3, the filtrate was dried
and concentrated to yield a white solid. Crude product was purified by column
chromatography using n-hexane:ethylacetate (3:1) mixture. Yield 14 g (91%).1H
NMR(400 MHz,CDCl3):d = 7.58(d,3J = 8.1 Hz, 1H,H-50),7.05(d,J = 2.3 Hz, 1H,H-
20), 6.93 (dd, 3J = 8.1 Hz, J = 2.3 Hz, 1H, H-60), 6.90 (s, 1H, H–CHBr2), 6.88 (s, 1H, H–
CHBr2),5.31–5.01(m,2H,H-1,H-3),4.54(s,1H,H-2),4.40–4.29(m,2H,H-4,H-6a),
4.05–3.80 (m, 2H, H-5, H-6b), 2.09–1.83 (m, 12H, H–CH3); IR (KBr): 3050, 2960,
1759, 1606,1576,1498, 1429,1368, 1240,1042,907,702,639,599 cmꢃ1;MS(FT-
ICR): m/z: 788.794 [M+Na]+, 802.773 [M+K]+.
29. 6-(2,3,4,6-Tetra-O-acetyl-D-glucopyranosyl)naphthalodinitrile 5: Method A:
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Soc. 1989, 111, 9125.
compound (7.68 g, 10 mmol) was stirred with fumaronitrile (780 mg,
4
10 mmol) and NaI (10 g) in dry DMF (100 mL) at 75–80 °C for 24 h.
Afterwards additional fumaronitrile (780 mg, 10 mmol) was added, the
reaction mixture was stirred for another 24 h. The cold solution was poured
into a solution of NaHSO3 in water. Precipitates formed were filtered, dried,
and purified by column chromatography with acetonitrile: DCM (1:9). Yield
3.4 g (65%).Method B: 6-hydroxynaphthalodinitrile 8 (1.36 g, 7 mmol) and
acetobromoglucose 9 were suspended in acetonitrile (100 mL). Silver(I) oxide
(2.32 g, 10 mmol) was added and the reaction mixture was heated at 50 °C for
24 h. The reaction mixture was cooled and filtered to remove inorganic salts
and the solvent was evaporated by rotary evaporator. The solid obtained was
purified by column chromatography using toluene acetone (4:1) mixture as
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solvent. Yield 2.53 g (71%). Mp: 190–192 °C. ½a D20
ꢄ
= ꢃ19 (c 0.8, CHCl3). 1H NMR
(400 MHz, DMSO-d6): d = 8.68 (s, 1H, H-10), 8.59 (s, 1H, H-40), 8.23 (d, J = 9.2 Hz,
1H, H-80), 7.84 (d, J = 2.3, 1H, H-50), 7.64 (dd, J = 9.2 Hz, J = 2.3 Hz, 1H, H-70),
5.79 (d, J = 7.9 Hz, 1H, H-1), 5.46 (t, J = 9.6 Hz, 1H, H-3), 5.31 (t, J = 7.9 Hz, 1H,
H-2), 5.21 (t, J = 9.6, 1H, H-4), 4.37–4.25 (m, 3H, H-5, H-6a,b), 2.03–2.01 (m,
12H, CH3); 13C NMR (100 MHz, CDCl3): d = 170.1, 170.7, 170.4, 170.1 (4C, C@O),
159.3 (1C, C60), 137.3 (1C, C-70), 137.2 (1C, C-50), 135.6 (1C, C-80), 131.0 (1C, C-
40), 124.4 (1C, C-10), 117.4 (1C, C-20), 117.3 (1C, C-30), 113.1 (1C, C-CN),111.6
(1C, C-CN), 99.1 (1C, C-1), 73.6 (1C, C-2), 73.3 (1C, C-3), 72.6 (1C, C-5), 72.0 (1C,
C-4), 68.9 (1C, C-6), 21.1, 21.0, 20.9, 20.8, 20.3 (4C, CH3): IR (KBr): 2958, 2234
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2005, 41, 1203–1212; (e) Brasseur, N.; Nguyen, T.-L.; Langlois, R.; Ouellet, R.;
Marengo, S.; Houde, D.; van Lier, J. E. J. Med. Chem. 1994, 37, 415–420; (f) Sun,
W.; Wang, G.; Li, Y.; Calvete, M. J. F.; Dini, D.; Hanack, M. J. Phys. Chem. A 2007,
111, 3263–3270.
(C „ N), 1755, 1623, 1597, 1500, 1465, 1369, 1233, 1040, 908, 822, 700 cmꢃ1
MS (FT-ICR): m/z: 547.132 [M+Na]+, 563.106 [M+K]+.
;
30. Woehrle, D.; Shopova, M.; Mueller, S.; Milev, A. D.; Mantareva, V. N.; Krastev, K.
K. Journal of Photochemistry and Photobiology, B: Biology 1993, 21, 155–165.
31. Synthesis of 10: Naphthalodinitrile 5 (1.0 g, 1.9 mmol) was suspended in dry
methanol (10 mL), cooled in ice bath while bubbling gaseous ammonia through
the suspension. At 0 °C Na metal (46 mg, 2 mmol) was added. After some time
the solid dissolved in methanol indicating the deprotection of acetyl groups of
sugar part. The reaction mixture now warmed slowly to room temperature and
then refluxed for 2 h while bubbling gaseous ammonia through the solution.
After completion of the reaction, the solution was cooled, ammonia gas
removed, and mixture was bubbled with air to remove excess of ammonia.
Precipitate formed was separated and dried to get the crude product, which
was used without further purification for the next step. Yield: 1.2 g (99%).1H
NMR (400 MHz, DMSO-d6, significant signals): d = 8.28 (s, 1H, H-10), 8.23 (s, 1H,
H-40), 8.02 (d, J = 9.2 Hz, 1H, H-80), 7.61 (s, 1H, H-50), 7.40 (dd, J = 9.2 Hz,
J = 2.3 Hz, 1H, H-70), 5.10 (d, J = 7.1 Hz, 1H, H-1), 3.80–3.72 (m, 2H), 3.55–3.41
(m, 4H), 3.37–3.28 (m, 4H), 3.24–3.18 (m, 2H, H-5), 1.22 (s, 1H), 0.89–0.75 (m,
13
1H); C NMR (100 MHz, DMSO-d6): d = 156.9 (1C, C60), 135.5 (1C, C-70), 131.9
(1C, C-50), 131.2 (1C, C-80), 129.7 (1C, C-40), 121.1 (1C, C-10), 120.4 (1C, C–NH2),
112.6 (1C, C–NH), 100.7 (1C, C-1), 77.5 (1C, C-2), 76.9 (1C, C-3), 73.6 (1C, C-5),

Z. Iqbal et al. / Tetrahedron Letters 50 (2009) 5681–5685
5685
70.0 (1C, C-4), 61.0 (1C, C-6): IR (KBr): 3381 (N–H, O–H), 2957, 1614, 1549,
1517, 1398, 1290, 1079, 1049 cmꢃ1; MS (FT-ICR): m/z: 374.13466 [M+Na]+.
32. Synthesis of 12: Method A: isoindoline 10 (373 mg, 1 mmol.) and DBU 2–3
drops were refluxed in 1 mL DMAE for 24 h. Reaction mixture was cooled to
room temperature and washed with methanol. Precipitate formed was
separated by centrifugation. Crude product was extracted with methanol in
Soxhlet apparatus. Yield 108 mg (29%).Method B: naphthalocyanine 11
(400 mg,) was dissolved in 2:1 mixture of DMSO/MeOH (15 mL). Catalytic
amount of CH3ONa was added and the reaction mixture was stirred at room
temperature overnight. Ion exchange resin amberlite IR-120H was added to
neutralize the solution. The solution was filtered to remove the resins.
Precipitation of the product was carried out by excess of acetone.
Precipitates formed were filtered and dissolved in small amount of water
and reprecipitated with acetone. The crude product was dried and purified
with reverse phase HPLC using water acetonitrile as eluent. Yield 257 mg
(93%).1H NMR (250 MHz, DMSO-d6, significant signals): d = 9.75 (s, 4H), 8.70 (s,
4H), 8.61 (d, J = 9.2, 4H), 8.24 (s, 4H),7.68 (d, J = 9.2, 4H), 5.38 (s, 4H), 3.98–3.94
(m, 12H), 3.77–3.42 (m, 28H); UV/Vis (DMSO): kmax (log ) = 773 (7.55), 688
(6.85), 344 (7.13) nm; MALDI–TOF MS: m/z 1488.325 [M]+.
33. Synthesis of 11: mixture of naphthalodinitrile (1.57 g, 3 mmol), p-
e
a
5
toluenesulfonic acid monohydrate (57 mg, 0.3 mmol), hexamethyldisilazane
(HMDS) (0.21 mL, 1 mmol), DMF (2 mL), and Zn(OAc)2ꢁ2H2O (330 mg,
1.5 mmol) in
a sealed glass tube was stirred and heated at 150 °C
overnight. The semisolid obtained was cooled and precipitated with
methanol–water (1:2) mixture. The precipitates obtained were dried and
chromatographed
naphthalodinitrile
first
with
ethylacetate
to
remove
unreacted
5
and then side products with ethylacetate containing
2–5% methanol. Yield 730 mg (45%).1H NMR (250 MHz, CD3OD-d4, significant
signals): d = 9.38 (br s, 8H), 8.38 (br s, 4H), 8.11 (br s, 4H), 7.45 (br s,
4H),5.91–5.68 (m, 4H), 5.39–5.29 (m, 4H), 5.23–5.06 (m, 12H), 4.85–4.48 (m,
8H), 2.25–2.06 (m, 48H); UV/Vis (DMSO): kmax (log
e) = 769 (5.46), 336
(5.05) nm; MALDI–TOF MS: m/z 2160.475 [M]+.