A highly versatile octasubstituted phthalocyanine scaffold for ex post chemical diversification

Article abstract of DOI:10.1055/S-0029-1218602

The TBDPS protecting group was conveniently employed for the convergent synthesis of a highly soluble, fully protected octa-peripheral (op) substituted phthalocyanine (Pc). After facile deprotection, ex post modification of this full-fledged Pc scaffold b

Full text of DOI:10.1055/S-0029-1218602

PAPER
741
A Highly Versatile Octasubstituted Phthalocyanine Scaffold for ex post
Chemical Diversification
Phthalocyanine
Sc
e
affoldfor
e
r
x
post Ch
w
emica
l
D
iversific
i
a
tion g J. Berthold,a Theo Schotten,*b Frank Hoffmann,a Joachim Thiema
a
University of Hamburg, Department of Chemistry, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany
CAN GmbH, Grindelallee 117, 20146 Hamburg, Germany
Fax +49(40)428385797; E-mail: schotten@can-hamburg.de
b
Received 11 September 2009; revised 3 November 2009
This work is dedicated to Jenny Berthold on the occasion of her 60th birthday.
Curiously, broad scope protection/deprotection sequences
and associated linker chemistry for the ex post modifica-
tion of phthalocyanines have not been reported so far.
Abstract: The TBDPS protecting group was conveniently em-
ployed for the convergent synthesis of a highly soluble, fully pro-
tected octa-peripheral (op) substituted phthalocyanine (Pc). After
facile deprotection, ex post modification of this full-fledged Pc scaf-
fold by various linkers was successfully achieved. This strategy
overcomes the downsides of widely established linear convergent
approaches under harsh conditions, which are not only destructive
to chemically sensitive substituents, but also detrimental to rapid di-
versification towards Pc libraries.
Herein, we introduce a fully protected, octa-peripheral
(op) substituted phthalocyanine scaffold, which can be
conveniently deprotected and subsequently ex post modi-
fied in a modular fashion under mild conditions. Starting
from inexpensive pyromellitic dianhydride (PMDA), the
TBDPS-protected phthalic anhydride 10 was obtained in
a nine-step synthesis.5 The TBDPS protecting group
turned out to be most suitable6 under the cyclotetrameriza-
tion conditions according to the protocol of Uchida et al.7
as well as for subsequent crystallization. H2Pc 11 and
ZnPc 12, 13 were synthesized in good yields, providing
structurally uniform products not contaminated with par-
tially deprotected or decomposed specimens (Scheme 1).
Key words: heterocycles, dendrimers, protecting groups, phthalo-
cyanine, ex post diversification, divergent strategy
Since their discovery early in the last century, phthalocy-
anines (Pc) have been of great academic as well as indus-
trial interest to chemists and physicists and have become
one of the most studied classes of organic molecules. The
plain core structure, due to its insolubility, was originally
used in blue or green pigments.1 Since then, manifold
variations in substitution patterns have harnessed phthalo-
cyanines for application in many important technical
fields, such as nonlinear optics (including optical limita-
tion), xerography (as photoconductors), optical data stor-
age (as the laser absorption layer within recordable
compact discs)2 molecular electronics, solar energy con-
version, catalysis, and as the active component of gas sen-
sors.3 The vast majority of these phthalocyanine
derivatives have been synthesized via a convergent cy-
clotetramerization of their appropriately substituted o-ph-
thalic precursors, thus conserving the initial substitution
pattern. However, the utmost harsh conditions prevailing
during the formation of the phthalocyanine ring system
severely restrict synthetic scope, thus offering only rela-
tively simple, robust structures with limited functionality.
Obviously, phthalocyanines with sensitive substituents,
e.g. peptides, carbohydrates etc., which are highly desir-
able for biomedical applications, are hard to access be-
cause they empirically do not survive the
cyclotetramerization. An alternative divergent route via a
straightforward ex post introduction of these ligands to a
full-fledged phthalocyanine scaffold is obstructed by the
lack of a suitable protective group and linker chemistry.4
Figure 1 ORTEP Plot of the asymmetric unit of a-(DMSO)ZnPc-
op-CH2OTBDPS (13) recrystallized from CH2Cl2–PE with a small
amount of DMSO; DMSO as fifth ligand.8 View perpendicular to the
Pc ring (for clarity, only the ipso C atoms of the phenyl rings and the
central C atom of the tert-butyl groups are shown); carbon = gray,
oxygen = red, nitrogen = blue, silicon = orange, sulfur = yellow,
zinc = purple. (For full crystallographic details, see Supporting Infor-
mation and CIF file.)
SYNTHESIS 2010, No. 5, pp 0741–0748
x
x
.
x
x
.2
0
1
0
Advanced online publication: 11.12.2009
DOI: 10.1055/s-0029-1218602; Art ID: T18009SS
© Georg Thieme Verlag Stuttgart · New York

742
H. J. Berthold et al.
PAPER
O
O
O
O
O
O
O
O
O
O
O
cat. PTSA⋅H2O
concd H2SO4, MS
LiAlH4, Et2O
reflux,16 h
2,2-dimethoxypropane
acetone, r.t., 24 h
O
O
EtO
EtO
OEt
OEt
EtO
EtO
OH
OH
EtO
EtO
EtOH, reflux,18 h
O
96%
96%
40%
O
O
1
2
3
4
LiAlH4, Et2O
reflux, 3 h
78%
TBDPS
TBDPS
TBDPS
TBDPS
cat. PTSA⋅H2O
imidazole
TBDPS-Cl (1.1 equiv)
DMF, r.t., 24 h
O
O
O
O
O
OH
O
Swern
acetone–water
r.t., 24 h
oxidation
O
O
O
O
HO
HO
18 h
H
H
97%
97%
98%
O
OH
O
5
TBDPS
TBDPS
6
8
7
TBDPS
O
TBDPS
O
NaBO3⋅4H2O
AcOH, 50 °C, 16 h
95%
HMDS (6 equiv)
DMF (1 equiv)
Zn(OAc)2 (0.25 equiv)
PTSA⋅H2O (0.1 equiv)
100→130 °C then
130 °C, 63 h
TBDPS
TBDPS
TBDPS
O
TBDPS
TBDPS
TBDPS
TBDPS
O
O
O
O
O
O
N
N
N
O
N
M
N
Ac2O
R
150 °C, 3 h
OH
OH
N
O
45% for
11
95%
O
N
N
75% for
12
O
O
O
TBDPS
9
10
66% for
13
O
O
TBDPS
TBDPS
11 ... M = 2⋅H
12 ... M = Zn2+, R = NH3
13 ... M = Zn2+, R = DMSO
Scheme 1 Synthesis of H2Pc 11 and ZnPc 12 and 13 starting from PMDA (1). For H2Pc 11 the addition of Zn(OAc)2 was omitted.
Depending on the workup and purification conditions two with an organic biphasic system composed of dimethyl
different ZnPc products were obtained. Precipitation from sulfoxide and petroleum ether. Aqueous workup of the
acetone afforded deep blue crystals of 12. When using a dimethyl sulfoxide phase provided the deprotected H2Pc-
solvent mixture (CH2Cl2–PE) containing a small amount op-CH2OH (14) or ZnPc-op-CH2OH (15) in quantitative
of dimethyl sulfoxide for recrystallization, a crop of tur- yields (Scheme 2). However, the metal-free H2Pc-op-
quoise crystals of 13 was obtained (Figure 1). Both crys- CH2OH (14) displayed limited solubility due to rapid ag-
talline lots were subjected to X-ray crystal structure gregation and, thus, was excluded from further experi-
analysis. Interestingly, the crystal structures of these ma- mentation. Albeit only soluble in a relatively small
terials were not identical. Both lots showed the expected
ZnPc structure, but differed with respect to the axial
ligand coordinated to the central zinc atom. For 12, this
axial ligand was identified as ammonia (NH3), which ob-
viously originated from the N,N-dimethylformamide in-
duced scission of hexamethyldisilazane.
The crystal structure of 13 showed evidence for dimethyl
sulfoxide as the axial ligand, accountable to the recrystal-
lization protocol (Figures 1 and 2), subsequently con-
firmed by elemental analysis. The axial coordination of
dimethyl sulfoxide and methanol to ZnPcs, respectively,
has precedence in the literature.8
For upscaling to multigram amounts, an optimized depro-
tection protocol was developed. Most conveniently, by
choosing triethylamine trihydrofluoride in tetrahydrofu-
ran for deprotection of 11 and 12/13, all volatiles could be
removed by evaporation after neutralization. The silylated
cleavage products were separated by extractive workup
Figure 2 ORTEP Plot of the asymmetric unit of a-(DMSO)ZnPc-
op-CH2OTBDPS (13) recrystallized from CH2Cl2–PE with a small
amount of DMSO; DMSO as fifth ligand.8 View parallel to the Pc
ring, showing that the zinc atom is positioned slightly above the Pc
plane; carbon = gray, oxygen = red, nitrogen = blue, silicon = orange,
sulfur = yellow, zinc = purple. (For full crystallographic details, see
Supporting Information and CIF file.)
Synthesis 2010, No. 5, 741–748 © Thieme Stuttgart · New York

PAPER
Phthalocyanine Scaffold for ex post Chemical Diversification
743
12, 13
Et3N⋅3HF
THF, r.t., 4 d
99%
Bu
Bu
HN
O
NH
O
R
O
R
O
O
O
O
O
OH
HO
O
O
O
O
Bu
Bu
Bu
N
H
O
O
R
R
N
H
O
O
O
O
OH
OH
O
O
HO
anhydride (10 equiv)
py, r.t., 3–6 d
N
N
R
R
N
N
N
N
N
N
N
N
Zn
N
N
Zn
N
N
Zn
N
BuNCO (2 equiv)
py, 50 °C, 64 h
N
N
N
N
77%
81–92%
H
N
H
N
N
N
N
N
N
HO
Bu
O
O
O
O
O
O
O
O
OH
HO
O
O
O
15
O
HN
NH
R
R
Bu
propargyl bromide
50% aq NaOH
DMSO, r.t., 3 d
Bu
53%
19
16 R = Me
17 R = Pr
18 R = (CH2)2CO2H
O
O
O
O
O
O
N
N
N
N
N
Zn
N
N
N
O
O
20
Scheme 2 Deprotection of 12 and 13 followed by divergent syntheses of ZnPcs by peripheral substitution of novel ZnPc-op-CH2OH (15) with
anhydrides, butyl isocyanate and propargyl bromide.
selection of solvents, mainly dimethyl sulfoxide and pyri- method for the regio- and stereoselective functionaliza-
dine, the novel ZnPc-op-CH2OH scaffold (15) holds high tion of biologically interesting molecules.11 The decora-
potential as progenitor for a vast range of new Pc-based tion of 20 with carbohydrate ligands by ‘clicking’ azido
molecules.9 Nevertheless, the eightfold, dendrimer like sugars will be reported in due course.
functionality of this scaffold demands clean, complete,
regio- and stereospecific reactions for all ex post derivati-
In summary, for the first time, we introduced a novel
methodology for the protection/deprotection of a versatile
zations in order to avoid the formation of intractable iso-
Pc core. Linker chemistry of broad synthetic scope allows
meric mixtures. Firstly, as a model reaction, peracylation
ex post modification of a full-fledged Pc scaffold. Thus,
the synthetic limitations associated with the utmost harsh
formation conditions during cyclotetramerization have
with carboxylic anhydrides in pyridine was chosen and
smoothly executed for three examples 16–18. Next, we re-
acted 15 with excess butyl isocyanate and conveniently
been overcome. Pc scaffold 15 and, in particular, the octa-
isolated the corresponding octa-carbamate 19 uniformly
alkynyl-substituted Pc 20 will serve as progenitors of
in high yields. This linker chemistry will allow rapid di-
highly complex Pcs. ‘Click’ chemistry has proven its via-
versification and optimization of Pc properties, e.g. in ma-
bility for the synthesis of delicate molecules frequently
terial sciences.
occurring in the biomedical field.12 Experimental proto-
However, from a medicinal chemistry point of view, ester cols are convenient and suitable for the rapid generation
and carbamate linkages, aside from prodrug approaches, of hitherto unknown Pc libraries of analytically pure sub-
seem unfavorable due to their putative metabolic liabili- stances in up to a multigram scale. The performance of the
ties. Taking this into account, we elaborated an alkylation novel method will be demonstrated by ‘clicking’ azido
protocol along the lines of Wang et al.10 by applying 50% sugars to 20 in due course.
aqueous sodium hydroxide–dimethyl sulfoxide as the re-
action medium. A clean peralkylation of 15 with propar-
Organic solvents used for reactions were of p.a. quality and used as
gyl bromide afforded ZnPc 20 in good yields (Scheme 2).
With the octa-propargyloxy derivative 20 in hand, access
is gained to a plethora of cycloaddition reactions. In par-
ticular, the 1,3-dipolar cycloaddition of azides with
alkynes, well-recognized as ‘Sharpless click chemistry’,
is well-established as a mild, robust, and high-yielding
purchased from Fisher Scientific, Merck, Acros, or SAF. Commer-
cial available starting compounds and reagents were used directly
without further purification from SAF, Lancaster, and Acros. Col-
umn chromatography was performed on Fluka silica gel 60 Å (40–
63 mm). Bulk solvents used for chromatography and extraction were
of technical grade. Analytic TLC was performed on aluminum
sheets pre-coated with silica gel 60 Å with a fluorescent indicator
Synthesis 2010, No. 5, 741–748 © Thieme Stuttgart · New York

744
H. J. Berthold et al.
PAPER
(Merck 60 F254), and detection was effected by UV light at 254 and
366 nm and/or visualized with various spray reagents such as 10%
H2SO4 in EtOH , acidic aq CAN soln, and ninhydrin in EtOH fol-
lowed by heating or by a dipping bath of alkaline KMnO4. 1H and
13C NMR spectra were recorded on Bruker AMX400, DRX500, or
AV400 NMR spectrometer. 1H and 13C NMR, respectively, calibra-
tion of the spectra depending on the solvent was used [d = 2.50/39.5
(DMSO-d6), d = 7.26/77.0 (CDCl3), d = 7.20/128.0 (C6D6), d = 3.50/
66.5 (1,4-dioxane-d8), d = 8.7/149.8 (pyridine-d5), and d = 2.7/30.1
(DMF-d7)]; mc = centered multiplet. 2D NMR techniques such as
HH-COSY, TOCSY, NOESY, edited HSQC, and HMBC were
phase was separated and the aqueous phase was washed with Et2O
(500 mL). The combined organic phases were evaporated to dry-
ness, redissolved in CHCl3 (500 mL), dried (Na2SO4), and concen-
trated to yield an orange oil (60 g). According to 1H NMR, the oil
consisted of the desired diethyl phthalate 3 (41 g, 40%) still contain-
ing the tetraethyl ester 2 (19 g). Column chromatography (silica gel,
gradient PE → 80% EtOAc–PE) of sample of crude oil (3.6 g) gave
analytically pure 3 (2.14 g, 7.58 mmol) as a pale yellow oil;
Rf = 0.24 (PE–EtOAc, 60:40).
1H NMR (400 MHz, DMSO-d6): d = 7.76 (s, 2 H, H3), 5.27 (br s, 2
H, OH), 4.58 (s, 4 H, H1), 4.28 (q, 3JH6,H7 = 7.0–7.3 Hz, 4 H, H6),
1.28 (t, 3JH6,H7 = 7.0–7.3 Hz, 6 H, H7).
13C NMR (100 MHz, DMSO-d6): d = 167.1 (C5), 142.7 (C2), 129.8
(C4), 126.0 (C3), 61.1 (C6), 59.2 (C1), 13.9 (C7).
used to assign the relative positions of protons and their carbons. 13
NMR resonances are reported as the proton-decoupled chemical
shifts, and in most cases the JMOD, PENDANT, or/and DEPT 13
C
C
NMR technique was used to differentiate carbons. MS (FAB+) spec-
tra were obtained on a VG 70S mass spectrometer with a xenon
FAB-gun and m-nitrobenzyl alcohol (3-NOBA) as matrix at 5000
resolution. MALDI-TOF mass spectrometric analysis were per-
formed on a Bruker Biflex III, positive mode (matrix: anthracene-
1,8,9-triol). 3D-Molecular structures from single crystals were ob-
tained after X-ray diffraction (XRD) analysis that was performed on
a Bruker SMART APEX 1 CCD irradiated with a diffraction ceram-
ic tube KFF-Mo-2K-90 (MoKa radiation, l = 71.073 pm) at 157 K
(Oxford Cryosystem, 700 series Cryostream Cooler). The raw data
were processed by Bruker AXS software package SMART APEX
5.0. UV-Vis spectra were recorded on a Perkin-Elmer dual-beam
Bio50; log e L/cm·mol. Melting points (uncorrected) were deter-
mined in an open capillary tube on an apotec – Otto Stein Inc. melt-
ing point apparatus.
HRMS (FAB+, 3-NOBA): m/z [M – OCH2CH3]+ calcd for
C12H13O5: 237.0757; found:237.0766 (100%); m/z [M + H]+ calcd
for C14H19O6: 283.1176; found: 283.1184 (50%).
Diethyl 3,3-Dimethyl-1,5-dihydro-2,4-benzodioxepine-7,8-di-
carboxylate (4)5a
The crude orange oil of 3 (34.6 g) was dissolved in THF (240 mL)
and stirred with 2,2-dimethoxypropane (100 mL, 816 mmol) and
PTSA·H2O (1.0 g, 5.3 mmol) for 24 h. The reaction was quenched
by addition of Et3N (1.5 mL, 11 mmol). Volatiles were removed in
vacuo and the resulting red-brown oil was dissolved in CHCl3 (300
mL) and washed consecutively with H2O (2 × 100 mL), sat. aq
NaHCO3 (2 × 200 mL), and brine, dried (Na2SO4), and concentrat-
ed to yield orange waxy crystals (41.4 g), which were used without
further purification in the next reaction. 1H NMR of the intermedi-
ate isolated reaction product still revealed contamination by tetra-
ethyl ester 2 in a ratio identical to the starting mixture. Analytically
pure 4 was obtained by reacting a sample of purified 3 (1.07 g, 3.80
mmol) in THF (12 mL, dried over MS) with 2,2-dimethoxypropane
(3.0 mL, 25 mmol) and PTSA·H2O (25 mg, 0.13 mmol) for 24 h.
The reaction was quenched by addition of Et3N (0.5 mL, 3.6 mmol).
The clear soln was evaporated to dryness, dissolved in EtOAc,
washed consecutively with aq 0.5 M NaOH, sat. aq NaHCO3, and
brine, dried (Na2SO4), and evaporated to yield 4 (1.16 g, 3.64 mmol,
96%) as pale yellow crystals; mp 85 °C; Rf = 0.66 (PE–EtOAc,
60:40).
Tetraethyl Benzene-1,2,4,5-tetracarboxylate (2)5a
PMDA (1, 50.0 g, 0.23 mol) was suspended in abs EtOH (500 mL)
and refluxed until a soln was formed. Concd H2SO4 (30 mL, 1.1
mol) was added dropwise and the mixture was refluxed for 18 h.
EtOH (350 mL) was distilled off from the reaction (atmospheric
pressure). The remaining soln was actively cooled to r.t. and poured
into cold (0 °C) 2 M NaOH (400 mL), while the internal tempera-
ture raised to 10 °C and a white precipitate was formed immediate-
ly. The aqueous phase was washed with MTBE (2 × 300 mL). To
the acidic water phase 2 M NaOH was added (pH >9) and the mix-
ture was washed with MTBE (100 mL). The combined organic
phases were washed subsequently with H2O and brine and dried
(Na2SO4). Filtration and evaporation gave a slightly yellowish,
highly viscous syrup; upon standing at r.t., white crystals formed;
yield: 80.5 g, 0.22 mol (96%); mp 54 °C.
1H NMR (500 MHz, DMSO-d6): d = 7.50 (s, 2 H, H3), 4.87 (s, 4 H,
H1), 4.26 (q, 3JH6,H7 = 6.9–7.3 Hz, 4 H, H6), 1.42 (s, 6 H, H13), 1.27
(t, 3JH6,H7 = 7.3 Hz, 6 H, H7).
13C NMR (125 MHz, DMSO-d6): d = 166.7 (C5), 142.0 (C2), 129.9
(C4), 126.6 (C3), 102.0 (C12), 63.3 (C1), 61.2 (C6), 23.4 (C13),
13.9 (C7).
1H NMR (400 MHz, DMSO-d6): d = 8.06 (s, 2 H, H3), 4.33 (q,
3
3JH6,H7 = 3JH10,H11 = 7.1 Hz, 8 H, H6/H10), 1.30 (t, JH6,H7
=
3JH10,H11 = 7.1 Hz, 12 H, H7/H11).
HRMS (FAB+, 3-NOBA): m/z [M + H]+ calcd for C17H23O6:
323.1489; found: 323.1503.
13C NMR (100 MHz, DMSO-d6): d = 165.3 (C1/C5), 133.9 (C2/
C4), 129.0 (C3), 62.0 (C6/C10), 13.8 (C7/C11).
HRMS (FAB+, 3-NOBA): m/z [M – OCH2CH3]+ calcd for
C16H17O7: 321.0969; found: 321.0982 (100%); m/z [M + H]+ calcd
for C18H23O8: 367.1387; found: 367.1399 (30%).
7,8-Bis(hydroxymethyl)-3,3-dimethyl-1,5-dihydro-2,4-benzo-
dioxepine (5)5a
The crude orange, waxy crystals of the dioxepine dicarboxylate 4
(40.5 g) were dissolved in Et2O (300 mL) and a suspension of
LiAlH4 (8.48 g, 223 mmol) in Et2O (300 mL) was added at a rate
that maintained a steady reflux. After addition, the yellow mixture
was refluxed 3 h. Small samples were taken and worked up in order
to monitor the progress of the reduction by LC-MS (2: tR = 3.21
min; 4: tR = 3.06 min; 5: tR = 2.02 min). After completion of the re-
duction, the yellow, heterogeneous mixture was cooled to r.t. and
carefully quenched by adding it to well-stirred sat. aq NaHCO3. The
organic phase was separated and the aqueous phase was washed
with EtOAc (2 × 100 mL). The combined organic phases were con-
centrated and dried (Na2SO4). Evaporation of the solvent yielded an
orange solid. Repeated recrystallization (MeOH) gave four crops of
5 (22.5 g, 94.3 mmol, 33% after 3 steps) as fine, white needles. An
Diethyl 4,5-Bis(hydroxymethyl)phthalate (3)5a
To a well-stirred soln of 2 (133 g, 362 mmol) in Et2O (860 mL) was
added a suspension of LiAlH4 (16.5 g, 435 mmol) in Et2O (600 mL)
at a rate that maintained a steady reflux. After addition, the yellow
mixture was refluxed 2.5 h. The progress of the reduction was mon-
itored by LC-MS (2: tR = 3.21 min; 3: tR = 2.25 min) after micro
workup; the starting material was found to predominate, hence, a
second portion of LiAlH4 (5.70 g, 150 mmol) in Et2O (200 mL) was
added as before and reflux continued overnight. The yellow, hetero-
geneous mixture was cooled to r.t. and carefully quenched by addi-
tion to freshly prepared well-stirred sat. aq Na2SO4 soln. Salts were
removed by filtration and washed with THF (500 mL). The organic
Synthesis 2010, No. 5, 741–748 © Thieme Stuttgart · New York

PAPER
Phthalocyanine Scaffold for ex post Chemical Diversification
745
analytical pure sample of 4 (2.03 g, 6.30 mmol) in Et2O (50 mL)
was subjected to the process described above using LiAlH4 (0.50 g,
13 mmol) in Et2O (30 mL). After workup, the remaining solid (1.29
g, 5.42 mmol, 86%) was suspended in Et2O by means of ultrasound,
chilled in a fridge, filtered, and washed with cold Et2O to give 5
(1.16 g, 4.89 mmol, 78%) as fine, white needles; mp 137 °C.
1H NMR (400 MHz, DMSO-d6): d = 7.11 (s, 2 H, H3), 5.02 (t,
3JOH,H5 = 5.4 Hz, 2 H, OH), 4.76 (s, 4 H, H1), 4.48 (d, 3JOH,H5 = 5.5
Hz, 4 H, H5), 1.41 (s, 6 H, H13).
HRMS (FAB+, 3-NOBA): m/z [M – H2O – H]+ calcd for
C42H47O3Si2: 655.3058; found: 655.3078 (100%); m/z [M – H]+
calcd for C42H49O4Si2: 673.3164; found: 673.3147 (50%); m/z [M]+
calcd for , C42H50O4Si2: 674.3242; found: 674.3195 (22%).
4,5-Bis[(tert-butyldiphenylsilyloxy)methyl]phthalaldehyde (8)5c
According to the procedure of Farooq,5c oxalyl chloride (0.65 mL,
7.70 mmol) was dissolved in CH2Cl2 (6 mL) and cooled to –78 °C.
A soln of DMSO (1.20 mL, 16.9 mmol) in CH2Cl2 (11.0 mL) was
added dropwise. The soln was stirred for 20 min and 7 (2.03 g, 3.00
mmol) dissolved in CH2Cl2 (6 mL) was added dropwise. The mix-
ture was stirred at –78 °C for 3 h and then Et3N (5.0 mL, 35.9 mmol)
was slowly added at –78 °C. The mixture was allowed to reach r.t.
overnight and then the yellow, heterogeneous mixture was diluted
with CH2Cl2 (200 mL), extracted with aq 2 M HCl, sat. aq NaHCO3,
and brine, and dried (Na2SO4). On evaporation gave 8 (1.95 g, 2.91
mmol, 97%) as a yellow, highly viscous oil. For analytical charac-
terization, adsorption on silica gel and subsequent column chroma-
tography (silica gel, gradient PE → 20% EtOAc–PE) yielded 8
(1.03 g, 1.53 mmol, 51%) as a colorless, highly viscous oil; Rf =
0.80 (PE–EtOAc, 80:20).
13C NMR (100 MHz, DMSO-d6): d = 137.5 (C4), 136.3 (C2), 124.6
(C3), 101.5 (C12), 63.9 (C1), 60.0 (C5), 23.7 (C13).
7,8-Bis[(tert-butyldiphenylsilyloxy)methyl]-3,3-dimethyl-1,5-
dihydro-2,4-benzodioxepine (6)5b
To a soln of 5 (20.4 g, 85.5 mmol) in anhyd DMF (150 mL) was
added imidazole (35.1 g, 516 mmol) in portions. An endothermic
enthalpy of solvation was observed. To the clear, colorless soln,
TBDPSCl (53.0 mL, 207 mmol) was added dropwise with a syringe
through a septum. A mild exothermic reaction occurred. After stir-
ring at r.t. for 24 h, MTBE (500 mL) was added to the clear, yellow
soln in order to precipitate imidazolium·HCl as a colorless solid.
The organic layer was filtered and consecutively washed with H2O
(2 × 300 mL), 2 M HCl (2 × 200 mL), buffer (pH ~5, 100 mL), sat.
aq NaHCO3 (100 mL), and brine and dried (Na2SO4). Concentration
yielded a clear, slightly yellow residue (67.9 g). The crude product
was further purified by column chromatography (silica gel, gradient
PE → 20% EtOAc–PE + 1 vol% Et3N) to yield 6 (59.2 g, 82.7
mmol, 97%) as a clear, colorless, highly viscous oil; Rf = 0.76 (PE–
EtOAc, 80:20).
1H NMR (400 MHz, DMSO-d6): d = 10.5 (s, 2 H, H1), 8.07 (s, 2 H,
H3), 7.54 (dd, 3JH7,H8 = 8.0 Hz, 4JH7,H9 = 1.3–1.5 Hz, 8 H, H7), 7.44
3
4
(tt, JH8,H9 = 7.4 Hz, JH7,H9 = 1.3–2.3 Hz, 4 H, H9), 7.35 (dd,
3JH7,H8 = 8.1 Hz, 3JH8,H9 = 7.4 Hz, 8 H, H8), 4.84 (s, 4 H, H5), 0.94
(s, 18 H, H11).
13C NMR (100 MHz, DMSO-d6): d = 192.5 (C1), 143.5 (C4), 135.2
(C2), 134.9 (C7), 132.2 (C6), 130.0 (C9), 127.9 (C8), 127.7 (C3),
62.6 (C5), 26.5 (C11), 18.7 (C10).
3
1H NMR (400 MHz, DMSO-d6): d = 7.54 (dd, JH7,H8 = 8.0 Hz,
HRMS (FAB+, 3-NOBA): m/z [M – O + H]+ calcd for C42H47O3Si2:
655.3058; found:655.3119 (100%); m/z [M – O + 2 H]+ calcd for
C42H48O3Si2: 656.3136; found: 656.3141 (49%); m/z [M + H]+ calcd
for C42H47O4Si2: 671.3007; found: 671.3027 (48%).
3
4JH7,H9 = 1.3–1.5 Hz,
4JH7,H9 = 1.3–2.3 Hz,
8
H, H7), 7.43 (tt, JH8,H9 = 7.4 Hz,
3
4
H, H9), 7.35 (dd, JH7,H8 = 8.1 Hz,
3JH8,H9 = 7.4 Hz, 8 H, H8), 7.10 (s, 2 H, H3), 4.77 (s, 4 H, H1), 4.70
(s, 4 H, H5), 1.42 (s, 6 H, H13), 0.91 (s, 18 H, H11).
4,5-Bis[(tert-butyldiphenylsilyloxy)methyl]phthalic Acid (9)5d
To a soln of 8 (21.8 g, 32.4 mmol) in AcOH (133 mL) was added
NaBO3·4 H2O (14.0 g, 91.0 mmol) in 1 portion and stirred at 50 °C
for 16 h. AcOH was removed by evaporation under reduced pres-
sure. The remaining white, crystalline residue was first sonicated
with EtOAc (3 × 100 mL) and decanted. The remaining insoluble
mass was dissolved in aq citric acid (0.5 wt%, 200 mL, pH ~3) and
extracted with EtOAc (100 mL). The combined organic phases
were washed consecutively with aq citric acid (pH ~3) and brine,
dried (Na2SO4), and concentrated to yield a white, crystalline solid
(21.7 g, 95%). Recrystallization (EtOAc–PE, 60 °C then storage in
a fridge) gave several crops of 9 (20.3 g, 28.9 mmol, 89%); mp 137
°C; Rf = 0.74 (t-BuOH–H2O–AcOH, 60:20:20).
13C NMR (100 MHz, DMSO-d6): d = 137.1 (C2), 135.8 (C4), 134.9
(C7), 132.6 (C6), 129.8 (C9), 127.8 (C8), 124.7 (C3), 101.6 (C12),
63.9 (C1), 63.0 (C5), 26.5 (C11), 23.6 (C13), 18.7 (C10).
HRMS (FAB+, 3-NOBA): m/z [M – H]+ calcd for C45H53O4Si2:
713.3477; found: 713.3510 (100%); m/z [M]+ calcd for
C45H54O4Si2: 714.3555; found: 714.3556 (65%); m/z [M + H]+ calcd
for C45H55O4Si2: 715.3633; found: 715.3549 (26%).
{4,5-Bis[(tert-butyldiphenylsilyloxy)methyl]-1,2-phe-
nylene}dimethanol (7)
Dioxepine 6 (2.54 g, 3.55 mmol) was completely dissolved in ace-
tone (134 mL). H2O (ca. 37 mL) was added slowly in portions until
opacity of the soln persisted. To this mixture, PTSA·H2O (86 mg)
was added at in one portion and the mixture was stirred at r.t. for 24
h. After 10 min the liquid already began to clarify. The reaction was
terminated by addition of Et3N until pH ~7–8. Evaporation to half
of the volume (ca. 80 mL) caused turbidity again. The mixture was
extracted with Et2O (3 × 100 mL). The combined organic phases
were washed consecutively with aq citric acid (0.5 wt%, pH ~3),
sat. aq NaHCO3, and brine, dried (Na2SO4), and concentrated to
yield 7 (2.38 g, 3.47 mmol, 98%) as a colorless, highly viscous oil;
Rf = 0.42 (PE–EtOAc, 60:40).
1H NMR (400 MHz, DMSO-d6): d = 13.1 (br s, 2 H, H1), 7.77 (s, 2
H, H3), 7.54 (dd, 3JH7,H8 = 8.0 Hz, 4JH7,H9 = 1.5 Hz, 8 H, H7), 7.44
3
4
(tt, JH8,H9 = 7.3–7.5 Hz, JH7,H9 = 1.3–2.3 Hz, 4 H, H9), 7.35 (dd,
3JH7,H8 = 8.0 Hz, 3JH8,H9 = 7.5 Hz, 8 H, H8), 4.77 (s, 4 H, H5), 0.93
(s, 18 H, H11).
13C NMR (100 MHz, DMSO-d6): d = 168.5 (C1), 140.2 (C4), 134.9
(C7), 132.3 (C6), 131.6 (C2), 129.9 (C9), 127.9 (C8), 126.5 (C3),
62.5 (C5), 26.4 (C11), 18.7 (C10).
HRMS (FAB+, 3-NOBA): m/z [M + H]+ calcd for C42H47O6Si2:
703.2906; found: 703.2913.
3
1H NMR (400 MHz, DMSO-d6): d = 7.57 (dd, JH7,H8 = 8.0 Hz,
4JH7,H9 = 1.3–1.5 Hz, 8 H, H7), 7.51 (s, 2 H, H3), 7.44 (tt,
4
3JH8,H9 = 7.4–7.6 Hz, JH7,H9 = 1.3–2.3 Hz, 4 H, H9), 7.35 (dd,
4,5-Bis[(tert-butyldiphenylsilyloxy)methyl]phthalic Anhydride
(10)5e
A degassed and argon flushed suspension of 9 (15.5 g, 22.0 mmol)
in Ac2O (300 mL) was stirred at 145–150 °C (oil bath) for 3 h with
exclusion of moisture. After cooling to 60 °C all volatiles were re-
moved under reduced pressure. The amorphous residue (16.2 g) was
washed (anhyd PE). Recrystallization (anhyd EtOAc, fridge) gave
3JH7,H8 = 8.1 Hz, 3JH8,H9 = 7.4 Hz, 8 H, H8), 5.09 (t, 3JOH,H1 = 5.3 Hz,
2 H, OH), 4.74 (s, 4 H, H5), 4.56 (d, 3JOH,H1 = 4.6 Hz, 4 H, H1), 0.92
(s, 18 H, H11).
13C NMR (100 MHz, DMSO-d6): d = 138.2 (C2), 135.7 (C4), 134.9
(C6), 132.7 (C7), 129.8 (C9), 127.8 (C8), 125.8 (C3), 63.3 (C5),
60.3 (C1), 26.5 (C11), 18.7 (C10).
Synthesis 2010, No. 5, 741–748 © Thieme Stuttgart · New York

746
H. J. Berthold et al.
PAPER
10 (14.5 g, 21.1 mmol, 95%); as pale yellow crystals; mp 118 °C.
These crystals were used for X-ray analysis.
SA·H2O (0.12 g, 0.60 mmol) was added to each vial. The vials were
sealed and placed in a pre-heated (100 °C) aluminum block when
the temperature was increased to 130 °C. The mixtures were stirred
at this temperature for 36 h. The pressurized, sealed vials were care-
fully opened after cooling to r.t. and the sticky, solid products were
combined (9.6 g), dissolved in CH2Cl2 and subjected to flash chro-
matography (silica gel, CH2Cl2 then gradient PE–EtOAc, 60:40 →
40:60) to give a crude crystalline product (5.3 g, 72%). Evaporation
of the solvents and recrystallization [PE–CH2Cl2 (90:10) with a
small amount of DMSO; fridge] gave two crops of 13 (3.66 g, 1.34
mmol, 49% and 1.29 g, 0.47 mmol, 17%) as turquoise shiny crys-
tals.
1H NMR (400 MHz, DMSO-d6): d = 8.06 (s, 2 H, H3), 7.54 (dd,
3JH7,H8 = 7.9 Hz, 4JH7,H9 = 1.5 Hz, 8 H, H7), 7.45 (tt, 3JH8,H9 = 7.3–
4
3
7.6 Hz, JH7,H9 = 1.2–2.1 Hz, 4 H, H9), 7.36 (dd, JH7,H8 = 7.9 Hz,
3JH8,H9 = 7.6 Hz, 8 H, H8), 4.89 (s, 4 H, H5), 0.94 (s, 18 H, H11).
13C NMR (100 MHz, DMSO-d6): d = 163.0 (C1), 146.6 (C4), 134.9
(C7), 132.0 (C6), 130.4 (C2), 130.0 (C9), 127.9 (C8), 122.4 (C3),
62.6 (C5), 26.4 (C11), 18.7 (C10).
HRMS (FAB+, 3-NOBA): m/z [M + H]+ calcd for C42H45O5Si2:
685.2800; found: 685.2817.
In the course of resynthesis on the same scale and using the proce-
dure as described above, 12 (75% yield) was isolated after heating
at 130 °C for 48 h and purification by flash chromatography (silica
gel) followed by precipitation from acetone. Fortunately, in the pre-
cipitate blue, opaque crystals were found appropriate for the X-ray
analysis of 12. Note: In order to prevent light-induced decomposi-
tion of the substance, protection from light is strongly recommend-
ed!
1H NMR (400 MHz, acetone-d6): d = 9.60 (s, 8 H, H3), 7.87–7.85
(m, 32 H, H7), 7.41–7.40 (m, 48 H, H8/H9), 5.58 (s, 16 H, H5), 1.18
(s, 72 H, H11).
1H NMR (400 MHz, DMSO-d6–CDCl3, 6:2): d = 9.42 (s, 8 H, H3),
7.73–7.71 (m, 32 H, H7), 7.35–7.31 (m, 48 H, H8/H9), 5.34 (br s,
16 H, H5), 1.08 (s, 72 H, H11).
13C NMR (100 MHz, DMSO-d6–CDCl3, 6:2): d = 153.2 (C1), 139.9
(C4), 137.2 (C2), 134.9 (C7), 132.6 (C6), 129.6 (C9), 127.6 (C8),
120.8 (C3), 64.4 (C5), 26.5 (C11), 18.8 (C10).
Crystal data for 10: C42H44O5Si2, Mr = 684.95, T = 153(2) K,
l = 0.71073 Å, triclinic, P1, a = 10.0725(10) Å, b = 12.3224(12) Å,
c = 16.1951(16) Å, V = 1875.0(3) Å3, Z = 2, Dx = 1.213 g cm–3,
F(000) = 728, m = 0.138 mm–1, crystal size 0.40 × 0.25 × 0.05
mm3, No. of unique data (Bruker AXS Smart APEX CCD area de-
tector using MoKa radiation) = 8363, No. of parameters = 448, R
(all data) = 0.0818, wR (all data) = 0.1030, r = 0.495 e Å–3.
R1 = 0.0521 [I > 2s(I), 5654 reflections]. CCDC deposition
number = 748149.
2,3,9,10,16,17,23,24-Octakis[(tert-butyldiphenylsilyloxy)meth-
yl]phthalocyanine (11)7
The reaction was conducted in two screw cap vials (each 50 mL)
which were charged in the following order with 10 (7.31 g, 10.7
mmol), HMDS (14.5 mL, 67 mmol), and DMF (0.82 mL, 10.6
mmol. The amounts were equally divided and a vigorous stream of
argon was bubbled through the stirred suspension for 5 min before
PTSA·H2O (0.11 g, 0.58 mmol) was added to each vial. The vials
were sealed and placed in a pre-heated (100 °C) aluminum block
when the temperature was increased to 130 °C. The mixtures were
stirred at this temperature for 10 h. The pressurized, sealed vials
were carefully opened after cooling to r.t. and the sticky, solid prod-
ucts were combined, dissolved in CH2Cl2 and subjected to flash
chromatography (silica gel, CH2Cl2 then gradient PE–EtOAc, 60:40
→ EtOAc → THF). Evaporation of the solvents and precipitation
from acetone gave two crops of 11 (2.50 g, 0.94 mmol, 45%) as a
blue powder; mp 263–264 °C. Note: In order to prevent light-in-
duced decomposition of the substance, protection from light is
strongly recommended!
MS (MALDI-TOF, anthracene-1,8,9-triol): m/z [M]+ calcd for
C168H176N8O8Si8Zn: 2721.1051; m/z (%) found: 2722.12 (100),
2723.14 (93), 2721.20 (93), 2724.10 (82), 2720.25 (74), 2725.08
(63), 2719.27 (47).
UV-Vis (THF): lmax (log e) = 675 nm (2.6–4.3 × 105).
Zinc–Ammonia Complex 12
Mp 294–296 °C.
Anal. Calcd for C168H176N8O8Si8ZnH2O: C, 73.55; H, 6.54; N, 4.08.
Found: C, 73.53; H, 6.72; N, 4.06.
1H NMR (400 MHz, CDCl3): d = 9.51 (s, 8 H, H3), 7.80–7.78 (m,
32 H, H7), 7.36–7.31 (m, 48 H, H8/H9), 5.35 (s, 16 H, H5), 1.16 (s,
72 H, H11), –0.17 (br s, 2 H, NH).
13C NMR (100 MHz, CDCl3): d = 150.5 (C1), 141.3 (C4), 136.1
(C2), 135.7 (C7), 133.4 (C6), 129.8 (C9), 127.8 (C8), 122.1 (C3),
65.0 (C5), 27.0 (C11), 19.4 (C10); (C1 and C2 were derived from
HMBC spectra).
Crystal data for 12:13 C168H179N9O8Si8Zn·2.5 acetone·H2O,
Mr = 2904.50, T = 153(2) K, l = 0.71073 Å, triclinic, P1,
a = 18.2775(18) Å, b = 19.700(2) Å, c = 24.290(2) Å,
V = 8148.5(14) Å3, Z = 2, Dx = 1.184 g cm–3, F(000) = 3092,
m = 0.271 mm–1, No. of unique data (Bruker AXS Smart APEX
CCD area detector using MoKa radiation) = 28579, No. of
parameters = 1876, R (all data) = 0.1506, wR (all data) = 0.1186,
r = 0.470 e Å–3. R1 = 0.0582 [I > 2s(I), 11703 reflections]. CCDC
deposition number = 748148.
MS (MALDI-TOF, anthracene-1,8,9-triol): m/z [M + H]+ calcd for
C168H179N8O8Si8: 2660.1995; m/z (%) found: 2661.19 (100),
2662.18 (90), 2660.22 (87), 2663.14 (60), 2659.25 (50), 2664.12
(37), 2665.12 (23).
UV-Vis (THF): lmax (log e) = 700 (665) nm (1.5 × 105).
Zinc–Dimethyl Sulfoxide Complex 13
Mp 239–241 °C.
Anal. Calcd for C168H176N8O8Si8Zn⋅DMSO: C, 72.83; H, 6.59; N,
4.00; S, 1.14. Found: C, 72.54; H, 6.64; N, 4.10; S, 1.12.
Anal. Calcd for C168H178N8O8Si8: C, 75.80; H, 6.74; N, 4.21. Found:
C, 75.68; H, 6.89; N, 4.18.
Crystal data for 13: C170H182N8O9SSi8Zn, Mr = 2803.39, T = 153(2)
K, l = 0.71073 Å, monoclinic, P21/c, a = 22.4151(19) Å,
b = 41.541(4) Å, c = 17.8269(16) Å, V = 15611(2) Å3, Z = 4,
Dx = 1.193 g cm–3, F(000) = 5952, m = 0.292 mm–1, crystal size
0.50 × 0.10 × 0.07 mm3, No. of unique data (Bruker AXS Smart
APEX CCD area detector using MoKa radiation) = 16078, No. of
parameters = 1795, R (all data) = 0.1573, wR (all data) = 0.1151,
r = 0.579 e Å–3. R1 = 0.0703 [I > 2s(I), 7995 reflections]. CCDC
deposition number = 748147.
{2,3,9,10,16,17,23,24-Octakis[(tert-butyldiphenylsilyloxy)meth-
yl]phthalocyaninato}zinc(II)–Ammonia Complex (12) or
{2,3,9,10,16,17,23,24-Octakis[(tert-butyldiphenylsilyloxy)meth-
yl]phthalocyaninato}zinc(II)–Dimethyl Sulfoxide Complex (13)7
The reaction was conducted in two screw cap vials (each 50 mL)
which were charged in the following order with 10 (7.46 g, 10.88
mmol), Zn(OAc)2 (0.51 g, 2.8 mmol), HMDS (13.4 mL, 65 mmol),
and DMF (0.85 mL, 11 mmol). A vigorous stream of argon was
bubbled through the stirred suspension for 5 min and then PT-
Synthesis 2010, No. 5, 741–748 © Thieme Stuttgart · New York

PAPER
Phthalocyanine Scaffold for ex post Chemical Diversification
747
2,3,9,10,16,17,23,24-Octakis(hydroxymethyl)phthalocyanine
(14)
13C NMR (100 MHz, DMSO-d6): d = 170.4 (C6), 151.2 (C1), 136.9
(C2), 135.5 (C4), 122.7 (C3), 63.9 (C5), 20.8 (C7).
Deprotection of 11 (2.50 g, 0.94 mmol) was analogously performed
as described for the synthesis of 15. After lyophilization a deep blue
solid (696 mg, 0.92 mmol, 98%) was isolated. Due to limited solu-
bility and rapid aggregation, characterization in concentrated soln,
as necessary for 13C NMR, could not be performed; mp >360 °C.
1H NMR (400 MHz, DMSO-d6): d = 9.00 (br s, 8 H, H3), 5.74 (br
s, 8 H, OH), 5.07 (s, 16 H, H5).
MS (MALDI-TOF, anthracene-1,8,9-triol): m/z [M + H]+ calcd for
C56H49N8O16Zn: 1153.2553; m/z (%) found: 1153.09 (100), 1154.07
(99.7), 1155.06 (87), 1152.11 (82), 1156.05 (80), 1157.05 (61),
1158.04 (33), 1159.04 (17).
Anal. Calcd for C56H48N8O16Zn·0.8 H2O: C, 57.54; H, 4.28; N, 9.59.
Found: C, 57.73; H, 4.58; N, 9.42.
13C NMR (100 MHz, DMSO-d6): d = 119.5 (C3), 60.7 (C5) via
HSQC 2D-NMR technique.
[2,3,9,10,16,17,23,24-Octakis(butyryloxymethyl)phthalocyani-
nato]zinc(II) (17)
To a sonicated soln of 15 (0.11 g, 0.13 mmol) in anhyd pyridine
(10.0 mL. 124 mmol) was added dropwise butyric anhydride (2.20
mL, 13.4 mmol) and the mixture was stirred in the dark at r.t. for 6
d. The solvent was evaporated, the remaining residue dissolved in
the minimum of THF (3 mL) and precipitated by dropwise addition
to PE (40 mL) then this was centrifuged. The supernatant was dis-
carded and the precipitate was washed with MeOH and dried under
vacuum to give 17 (0.16 g, 0.12 mmol, 92%); mp >360 °C.
MS (MALDI-TOF, anthracene-1,8,9-triol): m/z [M]+ calcd for
C40H34N8O8: 754.2494; m/z (%) found: 754.4 (100), 755.3 (90),
756.2 (41), 757.2 (12).
Anal. Calcd for C40H34N8O8·2 H2O: C, 60.75; H, 4.84; N, 14.17.
Found: C, 61.13; H, 4.88; N, 13.99.
[2,3,9,10,16,17,23,24-Octakis(hydroxymethyl)phthalocyani-
nato]zinc(II) (15); Typical Procedure
1H NMR (400 MHz, DMSO-d6): d = 8.72 (br s, 8 H, H3), 5.74 (br
A PTFE vessel with a screw cap was charged with 12 or 13 (3.15 g,
1.16 mmol) and dissolved in THF (200 mL). An initial amount of
Et3N·3 HF (4.0 mL, 75 mmol) was added and the mixture was
stirred for 3 h before a second portion of Et3N·3 HF (4.0 mL, 75
mmol) was added and the mixture was stirred overnight. The reac-
tion was monitored continuously by TLC, hence a final portion of
Et3N·3 HF (4.0 mL, 75 mmol) was added. According to TLC,
deprotection was completed after 3 d. The mixture was carefully
neutralized in portions by addition of a soln of NaOMe in MeOH.
The solvent was removed under reduced pressure and the residue
dissolved in DMSO (300 mL) and extracted with PE (8 × 100–150
mL) until no UV active spot could be detected on TLC. The DMSO
phase was separated and reduced to a minimum. The remaining
slurry was dropped into aq 2 M HCl and the precipitate thus formed
was collected by centrifugation. The resulting sticky, deeply blue
paste was repeatedly suspended in distilled H2O by using ultrasound
and centrifuged until the aqueous phase was neutral. Finally, the
product was lyophilized to give 15 (0.97 g, 1.18 mmol, 99%) as
free-flowing, fine flakes; mp >360 °C.
3
s, 16 H, H5), 2.60 (t, JH7,H8 = 7.0–7.3 Hz, 16 H, H7), 1.79 (sext,
3JH7,H8 = 3JH8,H9 = 7.3–7.5 Hz, 16 H, H8), 1.07 (quint, 3JH8,H9 = 6.3–
7.5 Hz, 24 H, H9).
13C NMR (100 MHz, DMSO-d6): d = 172.7 (C6), 151.1 (C1), 136.8
(C2), 135.5 (C4), 122.4 (C3), 63.8 (C5), 35.5 (C7), 18.1 (C8), 13.5
(C9).
Anal. Calcd for C72H80N8O16Zn: C, 62.72; H, 5.85; N, 8.13. Found:
C, 62.38; H, 6.03; N, 8.18.
{2,3,9,10,16,17,23,24-Octakis[(3-carboxypropanoyloxy)meth-
yl]phthalocyaninato}zinc(II) (18)
Upon sonication, 15 (100 mg, 124 mmol) was dissolved in anhyd
pyridine (10.0 mL, 124 mmol) and succinic anhydride (1.05 g, 10.5
mmol) was added and the mixture was stirred in the dark at r.t. for
6 d. After evaporation of the solvent, the remaining residue was
washed with EtOAc and centrifuged to remove the excess of anhy-
dride. The residue was dissolved in the minimum of DMSO (3 mL)
and dropwise added to MeCN (40 mL). The precipitate thus ob-
tained was dissolved again in DMSO (3 mL) and added dropwise to
deionized H2O (50 mL). The mixture was lyophilized and dried in
an evacuated desiccator over P4O10 for 5 d to yield 18 (170 mg, 105
mmol, 85%) as a blue, free-flowing powder; mp >360 °C.
1H NMR (400 MHz, DMSO-d6): d = 12.3 (br s, 8 H, H9), 8.96 (br
s, 8 H, H3), 5.76 (br s, 16 H, H5), 2.83 (t, 3JH7,H8 = 6.0–6.8 Hz, 16
H, H7), 2.67 (t, 3JH7,H8 = 6.3–6.8 Hz, 16 H, H8).
13C NMR (100 MHz, DMSO-d6): d = 173.4 (C9), 172.2 (C6), 151.7
(C1), 137.1 (C2), 135.8 (C4), 123.1 (C3), 64.1 (C5), 28.82 (C7),
28.77 (C8).
1H NMR (500 MHz, DMSO-d6): d = 9.40 (s, 8 H, H3), 5.72 (t,
3JOH,H5 = 5.4–5.7 Hz, 8 H, OH), 5.12 (d, 3JOH,H5 = 5.4 Hz, 16 H, H5).
13C NMR (125 MHz, DMSO-d6): d = 153.0 (C1), 141.7 (C4), 136.6
(C2), 120.0 (C3), 60.9 (C5).
MS (MALDI-TOF, anthracene-1,8,9-triol): m/z [M]+ calcd for
C40H32N8O8Zn: 816.1629; m/z (%) found: 816.80 (100), 818.80
(60), 817.81 (56), 820.79 (46), 819.80 (38), 821.80 (18).
UV-Vis (DMSO): lmax (log e) = 681 nm (6.7 × 105).
Anal. Calcd for C40H32N8O8Zn·3.5 H2O·0.5 DMSO: C, 54.04; H,
4.54; N, 12.30; S, 1.76. Found: C, 53.43; H, 4.57; N, 12.28; S, 1.67.
Anal. Calcd for C72H64N8O32Zn·5 H2O: C, 50.61; H, 4.36; N, 6.56.
Found: C, 50.77; H, 4.31; N, 6.87.
[2,3,9,10,16,17,23,24-Octakis(acetoxymethyl)phthalocyani-
nato]zinc(II) (16)
{2,3,9,10,16,17,23,24-Octakis[(N-butylcarbamoyloxy)meth-
yl]phthalocyaninato}zinc(II) (19)14
Upon sonication, 15 (0.109 g, 0.133 mmol) was dissolved in anhyd
pyridine (10.0 mL. 124 mmol), and Ac2O (3.0 mL, 32 mmol) was
added dropwise. The mixture was stirred in the dark at r.t. for 3 d.
Evaporation of the solvent and column chromatography (silica gel,
gradient PE–EtOAc, 40:60 → EtOAc → THF) followed by drying
yielded 16 (0.125 g, 0.108 mmol, 81%). Alternatively, instead of
column chromatography, purification was carried out by extraction
with EtOAc. The organic phase was washed with citric acid (pH ~3)
followed by sat. aq NaHCO3 and brine and dried (Na2SO4). Evapo-
ration yielded analytically pure 16; mp >360 °C.
Compound 15 (0.10 g, 0.13 mmol) was dissolved in anhyd pyridine
(10.0 mL, 124 mmol) by using ultrasound and then BuNCO (0.5
mL, 4.4 mmol) was added and the mixture was stirred in the dark at
r.t. for 4 d. Additional amounts of BuNCO were added after 4 d (0.3
mL, 2.7 mmol), 7 d (0.2 mL, 1.8 mmol), and 8 d (0.2 mL, 1.8
mmol), and DMAP (0.1 g, 0.82 mmol, 1 equiv) was added after 5 d.
According to TLC (THF), the conversion was still unsatisfactory,
hence after 8 d the mixture was warmed to 50 °C for 3 d. Volatiles
were removed by evaporation. The residue was dissolved in a min-
imum of pyridine (4 mL) by the means of ultrasound, precipitated
1H NMR (400 MHz, DMSO-d6): d = 8.77 (br s, 8 H, H3), 5.73 (br
s, 16 H, H5), 2.33 (s, 24 H, H7).
Synthesis 2010, No. 5, 741–748 © Thieme Stuttgart · New York

748
H. J. Berthold et al.
PAPER
by dropwise addition to MeCN (40 mL) and centrifuged to yield 19
(0.15 g, 0.10 mmol, 77%) as deep blue crystals; mp >295 °C (dec.).
Acknowledgment
We thank Prof. Kopf, Prof. Behrens, and Mrs. Nevoigt for perfor-
ming X-ray crystal structure analysis and Dr. Sinnwell for specific
NMR measurements.
1H NMR (400 MHz, DMSO-d6): d = 9.20 (br s, 8 H, H3), 7.59 (t,
3JNH,H7 = 5.1 Hz, 8 H, NH), 5.70 (br s, 16 H, H5), 3.19 (br d,
3
3JNH,H7 = 5.6 Hz, 16 H, H7), 1.55 (quint, JH7,H8 = 3JH8,H9 = 6.9–7.1
Hz, 16 H, H8), 1.41 (sext, 3JH8,H9 = 6.9 Hz, 3JH9,H10 = 7.1–7.4 Hz, 16
H, H9), 0.92 (dd, 3JH9,H10 = 7.1–7.4 Hz, 24 H, H10).
References
13C NMR (100 MHz, DMSO-d6): d = 156.2 (C1/C6, two overlap-
ping signals), 137.1 (C2), 136.8 (C4), 122.2 (C3), 63.6 (C5), 40.3
(C7, overlap with DMSO-d6; thus derived from HSQC), 31.6 (C8),
19.5 (C9), 13.6 (C10).
(1) (a) Lee, H.; Jung, J.; Deno, T.; Ohwa, M. WO 2008,095,801,
2008; Chem. Abstr. 2008, 149, 269526. (b) Metz, T.;
Schaefer, W. DE 102,007,033,191, 2009; Chem. Abstr.
2009, 150, 170268.
(2) (a) Emmelius, M.; Pawlowski, G.; Vollmann, H. W. Angew.
Chem., Int. Ed. Engl. 1989, 28, 1445. (b) Roth, K. Chem.
Unserer Zeit 2007, 41, 334.
(3) (a) McKeown, N. B. Phthalocyanine Materials: Synthesis,
Structure and Function, Vol. 6; Cambridge University
Press: Cambridge UK, 1998. (b) Leznoff, C. C.; Lever, A.
B. P. Phthalocyanines: Properties and Applications, Vol. 1-
4; VCH: New York, 1989-1996, .
(4) Juríček, M.; Kouwer, P. H. J.; Rehák, J.; Sly, J.; Rowan, A.
E. J. Org. Chem. 2009, 74, 21.
1H NMR (400 MHz, pyridine-d5): d = 9.49 (br s, 8 H, H3), 8.09 (br
s, 8 H, NH), 6.20 (br s, 16 H, H5), 3.54 (br s, 16 H, H7), 1.75 (br s,
3
16 H, H8), 1.49 (br d, JH9,H10 = 6.8 Hz, 16 H, H9), 0.92 (t,
3JH9,H10 = 6.8–7.1 Hz, 24 H, H10).
13C NMR (100 MHz, pyridine-d5): d = 157.4 (C1/C6), 123.7 (C3),
65.3 (C5), 41.3 (C7), 32.5 (C8), 20.3 (C9), 13.9 (C10) (C2 and C4
overlapping with pyridine-d5 signals).
Anal. Calcd for C80H104N16O16Zn: C, 59.64; H, 6.51; N, 13.91.
Found: C, 59.37; H, 6.65; N, 13.83.
(5) (a) Savage, P. B.; Gellman, S. H. J. Am. Chem. Soc. 1993,
115, 10448. (b) Corey, E. J.; Venkateswarlu, A. J. Am.
Chem. Soc. 1972, 94, 6190. (c) Farooq, O. Synthesis 1994,
1035. (d) McKillop, A.; Kemp, D. Tetrahedron 1989, 45,
3299. (e) Woehrle, D.; Eskes, M.; Shigehara, K.; Yamada,
A. Synthesis 1993, 194.
{2,3,9,10,16,17,23,24-Octakis[(prop-2-ynyloxy)methyl]phthalo-
cyaninato}zinc(II) (20)
To a vigorously stirred soln of 15 (0.10 g, 0.12 mmol) in DMSO (9
mL) was added aq NaOH (50 wt%, 0.90 mL, 17 mmol) to form a
gel-like suspension. Immediately, propargyl bromide (80 wt% in
xylene, 1.7 mL, 16 mmol) was added dropwise, and the mixture was
further stirred for 3 d in the dark. The resulting suspension was di-
luted with THF (25 mL) and EtOAc (75 mL), and poured into H2O
(100 mL). The organic phase was separated and consecutively
washed with aq 1 M HCl, sat. aq NaHCO3, and brine. The soln was
dried (Na2SO4) and concentrated to give crude material (450 mg)
that was purified by column chromatography (silica gel, PE–
EtOAc, 60:40 → EtOAc → THF). Appropriate fractions were com-
bined (180 mg) and evaporated. In order to remove still remaining
impurities, the material was precipitated from THF in MeOH and
isolated by centrifugation to yield 20 (72 mg, 64 mmol, 53%); mp
>360 °C.
(6) Overman, L. E.; Okazaki, M. E.; Mishra, P. Tetrahedron
Lett. 1986, 27, 4391.
(7) Uchida, H.; Yoshiyama, H.; Reddy, P. Y.; Nakamura, S.;
Toru, T. Synlett 2003, 2083.
(8) (a) Liu, W.; Jensen, T. J.; Fronczek, F. R.; Hammer, R. P.;
Smith, K. M.; Vicente, M. G. H. J. Med. Chem. 2005, 48,
1033. (b) Kobayashi, T.; Uyeda, N.; Suito, E. J. Phys. Chem.
1968, 72, 2446. (c) Stillman, M. J.; Thomson, A. J. J. Chem.
Soc., Faraday Trans. 2 1974, 805.
(9) Hassan, B. M.; Li, H.; McKeown, N. B. J. Mater. Chem.
2000, 10, 39.
(10) Wang, H.; Sun, L.; Glazebnik, S.; Zhao, K. Tetrahedron
Lett. 1995, 36, 2953.
(11) Bock, V. D.; Hiemstra, H.; Maarseveen, J. H. Eur. J. Org.
Chem. 2006, 51.
1H NMR (400 MHz, DMSO-d6): d = 8.86 (br s, 8 H, H3), 5.18 (br
4
s, 16 H, H5), 4.65 (d, JH6,H8 = 2.3 Hz, 16 H, H6), 3.72 (t,
4JH6,H8 = 2.3 Hz, 8 H, H8).
(12) (a) Bertozzi, C. R.; Agard, N. J.; Prescher, J. A.; Baskin, J.
M.; Sletten, E. M. US 2009,068,738, 2009; Chem. Abstr.
2009, 150, 330128. (b) Sletten, E. M.; Bertozzi, C. R. Org.
Lett. 2008, 10, 3097.
(13) Alternatively, the axial ligand of 12 might be interpreted as
H2O. However, there are two indications that the axial ligand
is NH3: 1. The distance is in accordance with a typical Zn–N
bond in such compounds, 2. calculation of both structural
models resulted in the smaller R value for NH3.
(14) (a) Plusquellec, D.; Lefeuvre, M. Tetrahedron Lett. 1987,
28, 4165. (b) Lin, T. S.; Antonini, I.; Cosby, L. A.;
Sartorelli, A. C. J. Med. Chem. 1984, 27, 813. (c) Duggan,
M. E.; Imagire, J. S. Synthesis 1989, 131.
13C NMR (100 MHz, DMSO-d6): d = 151.4 (C1), 137.0 (C2), 136.7
(C4), 121.7 (C3), 80.5 (C7), 77.8 (C8), 69.3 (C5), 57.8 (C6).
MS (MALDI-TOF, anthracene-1,8,9-triol): m/z [M]+ calcd for
C64H48N8O8Zn: 1120.2881; m/z (%) found: 1120.47 (100), 1122.43
(96), 1121.46 (87), 1123.41 (74), 1124.39 (73), 1125.39 (51),
1126.37 (24).
Anal. Calcd for C64H48N8O8Zn·2 H2O: C, 66.35; H, 4.52; N, 9.67.
Found: C, 66.13; H, 4.37; N, 9.36.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis. Included
are NMR, MALDI-TOF, UV-Vis spectra and single-crystal ORTEP
plots of selected compounds as well as drawings with assignment of
protons and carbons.
Synthesis 2010, No. 5, 741–748 © Thieme Stuttgart · New York