Towards control of dendrimer properties by reversible exchange of termini: Synthesis and characterization of diverse porphyrin dendrimers

Article abstract of DOI:10.1560/IJC.49.1.1

Porphyrin dendrimers with boronic ester, aldehyde, and pyridil termini were synthesized and fully characterized. These dendrimers have the potential to change their physical and chemical properties by reversible alteration of the reactive terminal groups.

Full text of DOI:10.1560/IJC.49.1.1

Israel Journal of Chemistry Vol. 49
DOI: 10.1560/IJC.49.1.1
2009
pp. 1–8
Towards Control of Dendrimer Properties by Reversible Exchange of Termini:
Synthesis and Characterization of Diverse Porphyrin Dendrimers
Meital SheMa-Mizrachi, anna aharoni, olga iliaShevSky, and n. gabriel leMcoff*
Department of Chemistry, Ben-Gurion University of the Negev, P.O. Box 653, Be’er Sheva 84105, Israel
(Received 14 July 2008 and in revised form 4 November 2008)
Abstract. Porphyrin dendrimers with boronic ester, aldehyde, and pyridil termini
were synthesized and fully characterized. These dendrimers have the potential to
change their physical and chemical properties by reversible alteration of the reactive
terminal groups.
IntroductIon
encapsulation of a porphyrin core within 1,3,5 phenyl-
ene dendron units, which provide highly efficient en-
ergy transfer through the dendron units to the porphyrin
core.7 Suslick and coworkers reported regioselective and
shape-selective oxidation with dendritic porphyrins.8
Herein we report on the synthesis of several types of
porphyrin core dendrimers with end groups that allow
reversible permutations of the termini. The possibility
to reversibly alter dendrimer termini may ultimately
lead to some control of the dendrimer properties in ar-
eas such as photo- and electrochemistry, catalysis, or
materials science.
Since their initial discovery in the early 1980s, den-
drimers have attracted the attention of chemists for both
their physical attributes and their challenging chem-
istry. Their properties and characteristics have been
studied and documented in the exponentially expanding
literature on the subject, and countless reviews have
been published in the area, although their challenging
synthetic procedures have undoubtedly reduced their
overall impact.3 It is thus of great interest to constantly
develop new synthetic techniques and methods for nov-
el dendritic macromolecules.
One of the main advantages of dendrimers is the
availability of numerous identical terminal groups.
Termini in dendrimers often determine not only solu-
bility and physical property parameters, but function
as well.4
We choose to synthesize boronic ester 1, aldehyde
3, and pyridil termini dendrimers 2 while using either
Fréchet type polybenzyl ether9 or Haag type polyglyc-
erols10 (Fig. 1) as dendritic backbones.
Dendrimer cores also have important functions, for
example in catalytic dendrimers.5 The attachment of
dendrons to metalloporphyrins produces catalytic den-
drimers with unusual photophysical and electrochemi-
cal redox behavior.6 For instance, Kimura et al. report
SyntheSIS of BoronIc eSter dendrImerS
Their unique properties as weak organic Lewis acids
*Author to whom correspondence should be addressed.
E-mail: lemcoff@bgu.ac.il

ꢀ
and their mild reactivity profile, coupled with their sta-
bility and ease of handling, make boronic esters a par-
ticularly attractive dendrimer terminal group.11 In spite
of that, there are very few reports of dendrimers contain-
ing boronic acid/ester terminal groups.1ꢀ
Boronic acid dendrimers may be easily transformed
to boronic-acid-terminated dendrimers by simple hy-
drolysis. Substrates such as alcohols and/or diols may
then be used for reversible binding to the terminal
groups. The overall process of boronic ester formation is
governed by a thermodynamic equilibrium and bestows
the dendrimer with the capacity to have dynamic envi-
ronments, which may influence dendrimer properties.
Scheme 1 shows the synthetic pathway followed. The
boronic ester dendrimers were successfully synthesized
by successive Williamson coupling reactions using 3,5-
dihydroxybenzyl alcohol act as the monomer unit. Den-
1
drimer 1 was fully characterized by H NMR and 13C
NMR, as well as by MALDI-TOF and LC-MS (Fig. ꢀ).
Pyridil-terminated dendrimers may also display dif-
ferent termini properties by reversible non-covalent
binding of different substrates due to the ability of the
piridyl nitrogen to act as a hydrogen-bond acceptor. The
synthesis of a pyridil-terminated dendrimer with a glyc-
erol-derived dendritic framework10 and a porphyrin core
is shown in Scheme ꢀ. The synthetic pathway for a G-ꢀ
dendron, where the focal hydroxyl moiety is protected
with a silyl ether group, was carried out by the divergent
approach based on a simple iterative two-step protocol
that involves allylation of an alcohol and subsequent
catalytic dihydroxylation of the allylic double bond with
osmium tetroxide and N-methyl morpholine-N-oxide as
a co-oxidant.10 The pyridil moieties were assembled via
the Sharpless “click” reaction,13 providing the G-ꢀ den-
dron in excellent yields. Following cleavage of the silyl
ether, the dendrons were coupled to the porphyrin core
via mesylation of the hydroxyl moiety. The glycerol
1
dendrimer was characterized by H NMR, 13C NMR,
and MALDI-TOF (Fig. 3).
SyntheSIS of Aldehyde dendrImerS
The nature of aldehyde-terminated dendrimers may be
easily modified due to the high and diverse reactivity of
the aldehyde function. Moreover, aldehyde end groups
may also be reversibly modified by imine formation or
acetalation. Thus, aldehyde-terminated dendrimers may
reversibly attach substrates with amine or diol function-
alities. There are only a small number of reports in the
literature related to aldehyde-terminated dendrimers.14
A prominent example by Majoral and coworkers reports
the synthesis of a phosphorus dendrimer bearing 600 al-
dehyde end groups in just 4 steps.15 Scheme 3 shows the
Fig. 1. Dendrimers synthesized in this study.
Israel Journal of Chemistry
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2009

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Fig. ꢀ. MALDI-TOF mass spectrum of boronic ester den-
drimer 1.
Scheme 1. Synthesis of boronic-ester-terminated dendrimer.
Scheme ꢀ. Synthesis of pyridil dendrimers.
Shema-Mizrachi et al. / Synthesis of Porphyrin Dendrimers

4
Fig. 4. MALDI-TOF mass spectrum of protected dendrimer 31.
dendrimer 3 were characterized by 1H NMR, 13C NMR,
and MALDI-TOF (Figs. 4 and 5).
In conclusion, we have shown the synthetic path-
ways towards the synthesis of three different types of
Fig. 3. MALDI-TOF spectrum of dendrimer 2.
synthetic pathway followed for the synthesis of a ꢀnd dendrimers bearing changeable terminal groups. Ongo-
generation porphyrin-core, aldehyde-terminated den- ing experiments will test the goal of controlling some
drimer. The protected dendrimer 31 and the aldehyde dendrimer properties, such as catalysis and/or solubil-
Scheme 3. Synthesis of aldehyde dendrimers.
Israel Journal of Chemistry
49
2009

5
General Procedure for Williamson Reaction of Dendritic
Benzyl Alcohol
[G1]-oh 9. [G0]-Br 7 (0.464 g, 1.6 mmol), 3,5-dihy-
droxybenzyl alcohol 8 (0.100 g, 0.7 mmol), KꢀCO3 (0.ꢀ48 g,
1.8 mmol), and 18-crown-6 (0.037 g, 0.1 mmol) in dry acetone
(30 mL) were heated at reflux temperature under nitrogen with
magnetic stirring for ꢀ4 h. After the solution was cooled, it
was poured into water (75 mL), extracted with diethyl ether
(4 ´ 50 mL), dried over NaꢀSO4, and filtered. The solvent was
evaporated in vacuo yielding a white solid (0.340 g, 84%).
1H NMR (CDCl3, 200 MHz) δ ppm = 1.34 (s, 24 H), 4.61 (s,
ꢀ H), 5.05 (s, 4 H), 6.5ꢀ (t, 1 H, J = 2 Hz), 6.60 (d, 2 H, J = 2
Hz), 7.41 (d, 4 H, J = 8 Hz), 7.82(d, 4 H, J = 8 Hz); 13C NMR
(CDCl3, 50 MHz) δ ppm = 20.8, 65.3, 69.9, 83.8, 101.3, 105.7,
1ꢀ6.5, 135.0, 139.9, 143.4, 160.1; MS (MALDI-TOF) m/z:
594.5 (M + Na+), 610.6 (M + K+). Calcd 57ꢀ.3.
Fig. 5. MALDI-TOF mass spectrum of dendrimer 3.
[G2]-oh 11 was obtained following the general proce-
dure. The solvent was removed and the residue was chromato-
graphed on silica gel (eluting with petroleum ether gradually
increasing to ethyl acetate) yielding a white solid (0.554 g,
ity, by reversibly varying the chemical nature of the
dendrimer termini.
1
47%). H NMR (CDCl3, 200 MHz) δ ppm = 1.34 (s, 48 H),
4.60 (s, 4 H), 4.95 (s, 4 H), 5.05 (s, 8 H), 6.49 (t, 1 H, J = 2 Hz),
6.55 (m, 4 H), 6.64 (d, 4 H, J = 2 Hz), 7.34 (d, 8 H, J = 8 Hz),
7.80 (d, 8 H, J = 8 Hz); 13C NMR (CDCl3, 50 MHz) δ ppm =
ꢀ4.8, 65.1, 69.8, 83.7, 101.0, 101.6, 105.6, 106.ꢀ, 1ꢀ6.5,
1ꢀ8.314, 134.9, 139.ꢀ, 139.9, 143.5, 159.9; MS (APCI) m/z:
1ꢀ46.9 (M + H+), 1ꢀ71.5 (M + Na+). Calcd 1ꢀ48.7.
experImentAl
General
All reactions were run under a dry nitrogen atmosphere.
Commercially available solvents and reagents were of reagent
grade quality and used without further purification, except for
acetone, which was dried over CaSO4 and freshly distilled; tol-
uene and THF, which were freshly distilled from sodium–ben-
zophenone; and dichloromethane, which was dried over acti-
vated molecular sieves 4A prior to use. All nuclear magnetic
resonance (NMR) spectra were acquired on a Bruker Avance
DPXꢀ00 or a Bruker Avance DMX500 spectrometer. Flash chro-
matography was performed with Davisil LC60A 40–63-µm
silica gel. Mass spectra were measured by a Bruker Dalton-
ics Reflex IV Matrix-Assisted Laser Desorption Ionization
Time-Of-Flight (MALDI-TOF) using dithranol,ꢀ,5-dihydroxy
benzoic acid (DHB), or trans-3-indole acrylic acid (IAA) as
matrices; or, alternatively by LC-MS, using a Bruker Esquire
3000plus (Bruker Daltonics). GC-MS analyses were done in
an Agilent 6850 GC-MS apparatus with Agilent Mass Selec-
tive Detector Gꢀ5577A and Agilent 19091S-443E HP-5MS
5% phenyl methyl siloxane column after dissolution of the
compounds in organic solvents. Preparative size exclusion
chromatography (SEC) was carried out with toluene or THF
eluent containing S-X1 or S-X3 Bio-Beads, ꢀ00–400 mesh
(Bio-Rad Laboratories).
[G2]-dendrimer 1. [Gꢀ]-Br 12 (0.777 g, 0.59ꢀ mmol),
5,10,15,ꢀ0-tetrakis (4-hydroxyphenyl) porphyrin 13 (0.050 g,
0.074 mmol), KꢀCO3 (0.10ꢀ g, 0.740 mmol), and 18-crown-6
(0.003 g, 0.01ꢀ mmol) in dry acetone (18 mL) were heated at
reflux under nitrogen with stirring for 48 h. The solvent was
evaporated in vacuo. The residue was purified by SEC (SX-1
in toluene) yielding a purple solid (0.ꢀ84 g, 68.5%). 1H NMR
(CDCl3, 200 MHz) δ ppm = –2.70 (s, 4 H), 34 (s, 194 H), 5.10
(s, 48 H), 5.31 (s, 8 H), 6.59 (t, 8 H, J = 2 Hz), 6.67 (m, 4 H),
6.76 (d, 16 H, J = 2 Hz), 6.91 (m, 8 H), 7.41 (m, 8 H), 7.45
(d, 34 H, J = 8 Hz), 7.85 (d, 34 H, J = 8 Hz), 8.17 (d, 8 H, J =
8 Hz), 8.91 (s, 8 H); 13C NMR (CDCl3, 50 MHz) δ ppm = 24.8,
69.9, 83.7, 101.6, 106.5, 113.0, 1ꢀ6.6, 1ꢀ8.3, 134.9, 135.7,
139.ꢀ, 139.4, 139.9, 158.6, 160.1; MS (MALDI-TOF) m/z:
5601.1 (M + H+). Calcd 560ꢀ.
General Procedure for Gn-Br
[G1]-Br 10. Under nitrogen to a stirred solution of
[G1]-OH 9 (ꢀ5.ꢀ00 g, 0.04 mol), were added triethylamine
(11.131 g, 0.1 mol) and methanesulfonyl chloride (10.584 g,
0.09 mol) in dry dichloromethane (1ꢀ60 mL) at 4 ºC. After
6 h stirring, the solution was washed with water, the organic
layer was dried, and volatiles were removed under reduced
pressure. Dry acetone (1ꢀ60 mL) was then added, followed
by lithium bromide (38.ꢀ58 g, 0.4 mol), and the solution was
refluxed overnight. After cooling, the acetone was removed
under reduced pressure; the residue was taken up in ethyl
acetate and the mixture was washed with water. The ethyl ac-
etate was removed under reduced pressure and the residue was
chromatographed on silica gel (eluting with petroleum ether
gradually increasing to ethyl acetate) followed by recrystal-
Materials
4-(4,4,5,5-tetramethyl-1,3,ꢀ-dioxaborolan-ꢀ-yl)benzal-
dehyde 5; ꢀ-(4¢-hydroxymethylphenyl)-4,4,5,5-tetramethyl-
1,3,ꢀ-dioxaborolan 6; ꢀ-(4¢-bromomethylphenyl)-4,4,5,5-tetra-
methyl-1,3,ꢀ-dioxaborolan 7; (allyloxy)triisopropylsilane 16;
and 4-azidopyridine were synthesized according to literature
procedures.16 4-(bromomethyl)benzaldehyde 23 was synthe-
sized by following a literature procedure17 with slight modifica-
tions. Other reagents were obtained from Aldrich and used as
received.
Shema-Mizrachi et al. / Synthesis of Porphyrin Dendrimers

6
lization (petroleum ether/ethyl acetate). A yellowish solid was
propargyl-[G-2]-tIpS (20). Compound 19 (3.35 g,
obtained (17.89 g, 64%).1H NMR (CDCl3, 200 MHz) δ ppm = 8.5 mmol) was added in portions to a stirred suspension of
1.36 (s, ꢀ4 H), 4.39 (s, 4 H), 5.05 (s, 4 H), 6.53 (t, 1 H, J = 2 NaH (ꢀ.03 g, 50.9 mmol) in dry DMF at 0 ºC. After the addi-
Hz), 6.63 (d, 4 H, J = 2 Hz), 7.42 (d, 4 H, J = 8 Hz), 7.84 (d, 4 tion was over, the mixture was stirred for 1 h at room tempera-
H, J = 8 Hz); 13C NMR (CDCl3, 50 MHz) δ ppm = 24.8, 33.5, ture. A solution of propargyl bromide (7.6 mL, 67.8 mmol)
69.9, 83.7, 10ꢀ.1, 108.1, 1ꢀ6.5, 1ꢀ8.5, 134.9, 139.6, 159.8; was added dropwise to the mixture at 0 ºC and stirring was
MS (APCI) 636.1 (M + H+), 657.ꢀ (M + Na+), 675.1 (M + continued for 30 min. The mixture was then stirred at room
K+). Calcd 635.
temperature for ꢀ4 h. The reaction mixture was poured into
[G2]-Br 12 was obtained using the general procedure water and extracted with ether. The combined organic layers
from [Gꢀ]-OH 11 yielding a yellowish solid (0.176 g, 73%). were washed with water, dried, and concentrated affording a
1H NMR (CDCl3, 500 MHz) δ ppm = 1.33 (s, 48 H), 4.39 (s, 4 brown oil, which was purified by flash chromatography (ethyl
H), 4.95 (s, 4 H), 5.05 (s, 8 H), 6.51 (t, 1 H, J = 2 Hz), 6.55 (t, 1 acetate/petroleum ether, 1:6) to give the desired 20 (diastereo-
1
H, J = 2 Hz), 6.60 (d, 4 H, J = 2 Hz), 6.65(d, 4 H, J = 2 Hz), 7.41 isomer mixture) as a light yellow oil (4.05g, 87%). H NMR
(d, 8 H, J = 8 Hz), 7.81(d, 8 H, J = 8 Hz); 13C NMR (CDCl3, (CDCl3, ꢀ00 MHz) δ ppm = 1.04–1.05 (m, 21 H), 2.39–2.44
50 MHz) δ ppm = 24.8, 33.5, 69.9, 83.7, 101.6, 102.1, 106.4, (m, 4 H), 3.47–3.91 (m, 15H), 4.17–4.18 (m, 4 H), 4.3ꢀ–4.33
108.1, 1ꢀ6.5, 135.9, 137.1, 138.9, 139.9, 160.1; MS (MALDI- (m, 4 H); 13C NMR (CDCl3, 50 MHz) δ ppm = 11.8, 17.9, 57.4,
TOF) m/z: 1340 (M + Na+), 1356.1 (M + K+). Calcd 1311.4.
57.5, 58.5, 63.1, 69.8, 70.1, 70.ꢀ, 71.3, 71.5, 74.ꢀ, 74.3, 74.6,
76.3, 76.5, 77.ꢀ, 77.6, 79.5, 79.6, 80.0, 80.3. MS (MALDI-
TOF) m/z: 549.05 (M + H+). Calcd 548.3.
General Procedure for the Synthesis of Dendritic
Polyglycerols by Dihydroxylation
pyridil-[G-2]-oh (21). A mixture of compound 20
A 4% osmium tetroxide solution in water (1 mL) was (1.38 g, ꢀ.5 mmol), Et3N (ꢀ.5 g, ꢀ5 mmol), 4-azidopyridine
added to a solution of the allyl ether (0.1 mol allyl equiv) and (1.3ꢀ g, 11 mmol), and 10 mol% of CuI was stirred for 48 h
N-methylmorpholine-N-oxide (0.11 mol) in acetone, water, at room temperature in methanol and water (1:1 solvents by
and t-BuOH (1:1:0.1 as solvents by volume). The mixture was volume). The reaction mixture was diluted with water and
then stirred for ꢀ4 h at room temperature. The solution was extracted with ethyl acetate; the combined organic layer was
extracted with ethyl acetate; the organic layer was dried with washed with brine and dried over MgSO4. After the removal
MgSO4, filtered, and the solvent evaporated.
of the solvent, the residue was purified on silica gel with ethyl
Allyl-[G-0]-tIpS (17). Compound 17 was prepared from acetate/methanol (10:1–1:1) to give the pyridine-terminated
16 according to the general dihydroxylation procedure. The Gꢀ-TIPS protected dendron (1.8 g, 1.7 mmol) (diastereoiso-
desired product (enantiomer mixture) was obtained as a yel- mer mixture) as a yellow solid. The protected dendron was
1
low oil (quant.). H NMR (CDCl3, ꢀ00 MHz) δ ppm = 1.04– dissolved in THF, and TBAF (1.ꢀ g, 3.4 mmol) was added.
1.19 (m, ꢀ1 H), 3.69–3.77 (m, 5H); 13C NMR (CDCl3, 50 MHz) The reaction mixture was stirred at room temperature for 1 h.
δ ppm = 11.7, 17.9, 64.0, 65.0,71.6; GC-MS (EI) m/z: ꢀ49.ꢀ THF was removed by evaporation under reduced pressure
(M + H+). Calcd ꢀ48.ꢀ.
and the crude product was purified on silica gel with ethyl
acetate/methanol (1:1). The desired product 21 (diastereoiso-
mer mixture) was obtained as a yellow solid (1.63 g, overall
yield 75%). 1H NMR (CD3OD, ꢀ00 MHz) δ ppm = 3.52–3.88
General Procedure for the Synthesis of Dendritic
Polyglycerols by Allylation
Allyl bromide (4 equiv for each OH group) was added to a (m, 15H), 4.68 (bs, 4 H), 4.83 (bs, 4 H), 7.83–7.91 (m, 8 H),
mixture of polyglycerol (1 equiv) and KOH (4 equiv for each 8.6ꢀ–8.69 (m, 14 H); 13C NMR (CD3OD, 50 MHz) δ ppm =
OH group) in anhydrous toluene under nitrogen. The reaction 6ꢀ.6, 64.ꢀ, 65.1, 71.7, 71.8, 78.1, 78.9, 79.0, 79.ꢀ, 79.3, 81.6,
mixture was stirred for 48 h at 90 ºC, and then cooled, washed 81.7, 115.1, 115.ꢀ, 1ꢀꢀ.9, 144.9, 147.6, 148.1, 15ꢀ.ꢀ, 15ꢀ.3;
with water, dried over MgSO4, and the solvent evaporated.
hydroxyl-[G-1]-tIpS (18). Compound 18 was prepared
MS (MALDI-TOF) m/z: 895.1 (M + Na+). Calcd 87ꢀ.9.
[G2]-dendrimer 2 Under nitrogen to a stirred solution of
from 17 according to the general allylation procedure. The de- pyridil-[G-ꢀ]-OH 21 (0.44 g, 0.5 mmol), were added trieth-
sired product (enantiomer mixture) was obtained as a yellow ylamine (0.077 g, 0.76 mmol) and methanesulfonyl chloride
1
oil (97%). H NMR (CDCl3, ꢀ00 MHz) δ ppm = 1.05–1.20 (0.07 g, 0.6 mmol) in dry THF (8 mL) at 4 ºC. After 1 h stir-
(m, ꢀ1 H), 3.45–3.76 (m, 5H), 3.99–4.17 (m, 4 H), 5.1ꢀ–5.17 ring, the solution was washed with water and dichloromethane,
(m, 4 H), 5.ꢀꢀ–5.31 (m, 4 H), 5.84–5.99 (m, 4 H); 13C NMR the organic layer was dried and volatiles were removed under
(CDCl3, 50 MHz) δ ppm = 11.8, 17.9, 63.1, 70.1, 71.4, 72.3, reduced pressure. Dry acetone (ꢀ0 mL) then was added fol-
76.9, 116.6, 116.7, 134.8, 135.3; GC-MS (EI) m/z: ꢀ85.ꢀ lowed by 5,10,15,ꢀ0-tetrakis (4-hydroxyphenyl) porphyrin 13
(M+ – iPr). Calcd 3ꢀ8.ꢀ.
(0.043 g, 0.063 mmol) and KꢀCO3 (0.07 g, 0.50 mmol), and the
Allyl-[G-1.5]-tIpS (19). Compound 19 was prepared mixture was heated at reflux under nitrogen with stirring for
from 18 according to the general hydroxylation procedure. 48 h. The solvent was evaporated in vacuo. The residue was
The desired product (diastereoisomer mixture) was obtained purified by SEC (SX-1 in THF) column yielding a purple solid
1
as yellow oil (93%). H NMR (ꢀ00 MHz) CDCl3 ppm δ = (0.1ꢀ9 g, 50%). 1H NMR (CDCl3, 500 MHz) δ ppm = –2.81 (s,
0.7ꢀ–0.76 (m, ꢀ1 H), 3.08–3.53 (m, 19 H); 13C NMR (CDCl3, 4 H), 3.77–4.37 (m, 60H), 4.78–4.81 (m, 16 H), 4.96–5.0ꢀ (m,
50 MHz) δ ppm = 13.2, 18.8, 64.7, 71.7, 72.0, 72.4, 73.2, 74.0, 16 H), 7.ꢀ5–7.ꢀ8 (m, 8 H), 7.65–7.71 (m, 34 H), 8.04–8.08
81.3, 81.5; GC-MS (EI) m/z: 353.ꢀ (M+ – iPr). Calcd 396.3.
(m, 8 H), 8.19–8.ꢀ5 (m, 8 H), 8.34–8.36 (m, 8 H), 8.63–8.66
Israel Journal of Chemistry
49
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7
(m, 8 H), 8.79 (s, 8 H); 13C NMR (CDCl3, 1ꢀ5 MHz) δ ppm = 105.7, 103.5, 101.3, 69.7, 67.9, 65.3; LC-MS (ESI) m/z: 487.1
63.7, 64.6, 68.1, 70.9, 71.3, 71.4, 71.5, 71.6, 71.7, 76.7, 76.9, (M + Na+), 503.1 (M + K+). Calcd 464.1.
77.ꢀ, 78.3, 77.8, 77.9, 11ꢀ.7, 11ꢀ.8, 113.5, 1ꢀ0.3, 1ꢀ0.5, 1ꢀ5.5,
134.7, 135.8, 14ꢀ.9, 151.6, 158.4, 158.5; MS (MALDI-TOF) 25 (0.ꢀꢀ g, 1.3 mmol), and triphenylphosphine (PPh3) (0.80 g,
m/z: 4098.5 (M + H+). Calcd 4098.ꢀ.
3.0 mmol) in THF (4 mL) at 0 ºC, was added dropwise a
[G2-co2me] (28). To a mixture of 27 (1.40 g, 3.00 mmol),
4-(Bromomethyl)benzaldehyde (23). 22 (ꢀ5.5ꢀ g, solution of diisopropyl azodicarboxylate (DIAD) (0.6 mL,
130.ꢀ mmol) was dissolved in dry toluene (400 mL) and cooled 3.0 mmol) in THF (16 mL). The reaction was warmed to room
to 0 ºC. 1M DIBAL in toluene (195 mL, 195 mmol) was added temperature and stirred for ꢀ4 h. The reaction was stopped
dropwise and the reaction mixture was stirred at 0 ºC for 1 h. by adding water and the mixture evaporated to remove THF.
Then chloroform (ꢀ00 mL) and ꢀN HCl (300 mL) were added The aqueous layer was extracted twice with ethyl acetate, and
and the reaction mixture was stirred at room temperature over- each organic layer was washed with 1 M aqueous KOH and
night. The organic layer was separated and washed twice with an equal volume of water. The combined organic layers were
water, dried over MgSO4, filtered, and evaporated to afford the dried over NaꢀSO4, filtered, and evaporated. The residue was
desired product as white flakes (21.45 g, 83%).
chromatographed on basic alumina (90/10 to 50/50 petroleum
2-(4-(Bromomethyl)phenyl)-1,3-dioxolane(24).18 23 ether/ethyl acetate) followed by an SEC preparative column
(5.91 g, ꢀ9.7 mmol) and p-toluenesulfonic acid monohydrate (SX-3 in toluene) to afford the desired product as a white foam
(0.19 g, 0.99 mmol) were dissolved in toluene (ꢀ00 mL). Eth- (0.56 g, 40%). 1H NMR (CDCl3, 200 MHz) δ ppm = 7.50 (d,
ylene glycol (4.9 mL, 88 mmol) was added and the reaction 8 H, J = 8 Hz), 7.43 (d, 8 H, J = 8 Hz), 7.28 (d, 4 H, J = 2 Hz),
mixture was refluxed for 24 h; water was removed using a 6.77 (t, 1 H, J = 2 Hz), 6.67 (d, 4 H, J = 2 Hz), 6.55 (t, 4 H, J = 2
Dean–Stark trap. After cooling to room temperature KꢀCO3 Hz), 5.83 (s, 4 H), 5.05 (s, 8 H), 4.99 (s, 4 H), 4.16–3.99 (m, 16
(about 14 g) was added and the mixture was stirred for 30 H), 3.91 (s, 3H); 13C NMR (CDCl3, 50 MHz) δ ppm = 166.7,
min, filtered and evaporated to afford the desired product as 160.0, 159.6, 138.8, 137.8, 131.9, 1ꢀ7.4, 1ꢀ6.7, 108.4, 107.1,
a yellow powder (6.3ꢀ g, 88%). 1H NMR (CDCl3, ꢀ00 MHz) 106.4, 103.4, 101.7, 70.0, 69.7, 65.ꢀ, 5ꢀ.ꢀ; MS (MALDI-TOF)
δ ppm = 7.46 (d, 4 H, J = 8 Hz), 7.40 (d, 4 H, J = 8 Hz), 5.82 (s, m/z: 1083.0 (M + Na+), 1099.0 (M + K+). Calcd 1060.4.
1 H), 4.49 (s, 4 H), 4.16–3.99 (m, 4 H); 13C NMR (CDCl3, 50
[G2-ch2oh] (29). To a suspension of LAH (0.016 g, 0.4ꢀ
MHz) δ ppm = 138.6, 138.2, 129.1, 126.9, 103.2, 65.3, 32.9; mmol) in THF (5 mL) cooled to 0 ºC, was added dropwise a
GC-MS (EI) m/z: M+ = 241.0 (12), M+ = 243.0 (12), 163.2 solution of 28 (0.15 g, 0.14 mmol) in THF (10 mL). Then, the
(100), 119.ꢀ (18), 91.1(58), 73.0 (14). Calcd ꢀ41.0.
solution was allowed to warm to room temperature and stirred
[G1-co2me] (26). A solution of 25 (1.90 g, 11.3 mmol), for ꢀ4 h. Excess LAH was quenched by slow addition of a
24 (6.3ꢀ g, ꢀ6.0 mmol), KꢀCO3 (3.59 g, ꢀ6.0 mmol) and 18- semi-saturated solution of NaꢀSO4. The THF was removed
crown-6 (0.32 g, 1.2 mmol) in acetone (90 mL) was refluxed under reduced pressure. The resultant aqueous solution was
for ꢀ4 h. Then, acetone was removed under reduced pressure. extracted twice with ethyl acetate. The combined organic lay-
Water was added to the residue and the resultant mixture was ers were dried over NaꢀSO4, filtered, and evaporated to afford
1
extracted twice with ethyl acetate. The organic layer was dried the desired product as a yellow oil (0.1ꢀ g, 83%). H NMR
over MgSO4, filtered, and evaporated to afford the desired (CDCl3, 500 MHz) δ = 7.47 (d, 8 H, J = 8 Hz), 7.41 (d, 8 H,
1
product as a white powder (5.40 g, 97%). H NMR (CDCl3, J = 8 Hz), 6.64 (d, 4 H, J = 2 Hz), 6.54 (d, 4 H, J = 2 Hz),
200 MHz) δ ppm = 7.50 (d, 4 H, J = 8 Hz), 7.43 (d, 4 H, J = 6.53 (t, 4 H, J = 2 Hz) 6.49 (t, 1 H, J = 2 Hz), 5.82 (s, 4 H),
8 Hz), 7.ꢀ7 (d, 4 H, J = 4 Hz), 6.76 (t, 1 H, J = 2 Hz), 5.83 (s, 5.04 (s, 8 H), 4.96 (s, 4 H), 4.56 (s, ꢀ H), 4.14–4.0ꢀ (m, 16 H);
4 H), 5.08 (s, 4 H), 4.17–3.99 (m, 8 H), 3.89 (s, 3H); 13C NMR 13C NMR (CDCl3, 125 MHz) δ ppm = 160, 159.9, 143.5,
(CDCl3, 50 MHz) δ ppm = 166.7, 159.6, 137.8, 137.5, 132.0, 139.3, 137.8, 137.6, 1ꢀ7.4, 1ꢀ6.7, 106.ꢀ, 105.6, 103.5, 101.6,
1ꢀ7.4, 1ꢀ6.8, 108.4, 107.3, 103.4, 69.9, 65.3, 5ꢀ.3; GC-MS 101.ꢀ, 69.8, 69.7, 65.3, 65.1; MS (MALDI-TOF) m/z: 1058.0
(EI) m/z: M+ = 492.2 (3), 163.2 (75), 119.2 (8), 91.1 (100), (M + Na+). Calcd 103ꢀ.4.
73.0 (18). Calcd 49ꢀ.ꢀ.
[G2-ch2omes] (30). To a stirred solution of 29 (1.155 g,
[G1-ch2oh] (27). To a suspension of lithium aluminum 1.1ꢀ mmol), were added triethylamine (0.ꢀ36 mL, 1.68 mmol)
hydride (LAH) (1.ꢀ5 g, 3ꢀ.7 mmol) in THF (50 mL) cooled to and methanesulfonyl chloride (0.105 mL, 1.35 mmol) in
0 ºC, was added dropwise a solution of 26 (5.40 g, 11.0 mmol) dichloromethane (15 mL) at 0 ºC for ꢀ h. Then the solution
in THF (90 mL). Then, the solution was allowed to warm was washed with water and the organic layer was dried over
to room temperature and stirred for ꢀ4 h. Excess LAH was NaꢀSO4, filtered, and evaporated to afford the desired product
quenched by slow addition of a semi-saturated solution of as a yellowish oil (1.15ꢀ g, 93%). 1H NMR (CDCl3, 500 MHz)
NaꢀSO4. THF was removed under reduced pressure. The resul- δ ppm = 7.48 (d, 8 H, J = 8 Hz), 7.42 (d, 8 H, J = 8 Hz), 6.64 (d,
tant aqueous solution was extracted twice with ethyl acetate. 4 H, J = 2 Hz), 6.60–6.59 (m, 3 H ), 6.54 (t, 4 H, J = 2 Hz) 5.82
The combined organic layers were dried over NaꢀSO4, filtered, (s, 4 H), 5.14 (s, 4 H), 5.03 (s, 8 H), 4.97 (s, 4 H) 4.15–4.06
and evaporated to afford the desired product as a white pow- (m, 16 H), ꢀ.8ꢀ (s, 3H); 13C NMR (CDCl3, 125 MHz) δ ppm =
der (4.81 g, 94%). 1H NMR (CDCl3, 200 MHz) δ ppm = 7.49 160.0, 138.8, 137.8, 137.7, 137.6, 1ꢀ7.4, 1ꢀ6.7, 107.6, 106.3,
(d, 4 H, J = 8 Hz), 7.42 (d, 4 H, J = 8 Hz), 6.59 (d, 4 H, J = 103.4, 10ꢀ.9, 101.6, 71.4, 69.9, 69.7, 65.3, 38.4; MS (MALDI-
ꢀ Hz), 6.51 (t, 1 H, J = 2 Hz), 5.82(s, 4 H), 5.05 (s, 4 H), 4.7 TOF) m/z: 1114.4 (M + H+). Calcd 1110.4.
(s, 1 H) 4.61 (s, 4 H), 4.17–3.99 (m, 8 H); 13C NMR (CDCl3,
[G2]-dendrimer (31). Asolution of 30 (0.51 g, 0.5 mmol),
50 MHz) δ ppm = 160.0, 143.4, 137.9, 137.6, 127.4, 126.7, 5,10,15,ꢀ0-tetrakis (4-hydroxyphenyl) porphyrin 13 (0.039 g,
Shema-Mizrachi et al. / Synthesis of Porphyrin Dendrimers

8
0.057 mmol), KꢀCO3 (0.079 g, 0.57ꢀ mmol), and 18-crown-
6 (0.002 g, 0.009 mmol) in acetone (40 mL) was refluxed
for 48 h. Then acetone was removed under reduced pres-
sure. To the resultant solid, was added water and the aqueous
layer was extracted twice with dichloromethane. The organic
layer was dried over sodium sulfate, filtered, and evaporated.
The residue was purified by SEC (SX-1 in THF) yielding a
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Dendritic Architectures; Reinhoudt, D.N., Ed.; Wiley:
Chichester, 1999.
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1
purple solid. (0.159 g, 58%). H NMR (CDCl3, 500 MHz) δ
ppm = 8.87(s, 8 H), 8.12 (d, 8 H, J = 8 Hz), 7.46 (d, 34 H, J =
8 Hz),7.41 (d, 34 H, J = 8 Hz),7.35 (d, 8 H, J = 8 Hz), 6.87
(d, 8 H, J = 2 Hz), 6.72 (d, 16 H, J = 2 Hz), 6.63 (t, 4 H, J =
ꢀ Hz), 6.55 (d, 8 H, J = 2 Hz), 5.78 (s, 16 H), 5.27 (s, 8 H),
5.05 (s, 48 H), 4.08–3.96 (m, 64 H), –ꢀ.75 (s, 4 H); 13C NMR
(CDCl3, 125 MHz) δ ppm = 160.1, 160.2, 139.5, 139.3, 137.8,
137.7, 135.7, 1ꢀ7.4, 1ꢀ6.7, 113.1, 106.7, 106.5, 101.7, 103.4,
70.3, 70.0, 69.7, 65.ꢀ; MS (MALDI-TOF) m/z: 4739.9 (M +
H+). Calcd 4735.8.
[G2]-dendrimer3. Asolutionof31(0.056g,0.01ꢀ mmol),
in THF (ꢀ0 mL) and HCl 1.5 M (5 mL) was stirred overnight.
Then THF was removed under reduced pressure. To the resul-
tant solid, was added water and the aqueous layer was extract-
ed twice with dichloromethane. Then the organic layer was
washed with NaHCO3 and brine. The organic layer was dried
over NaꢀSO4, filtered, and evaporated yielding a purple solid
(0.046 g, 95%). 1H NMR (CDCl3, 500 MHz) δ ppm = 9.91 (s,
16 H), 8.84 (s, 8 H), 8.10 (d, 8 H, J = 8 Hz), 7.79 (d, 32 H, J =
8 Hz), 7.51 (d, 3ꢀ H, J = 8 Hz), 7.32 (d, 8 H, J = 8 Hz), 6.84 (d,
8 H, J = 2 Hz), 6.73 (d, 16 H, J = 2 Hz), 6.57 (t, 4 H, J = 2 Hz),
6.55 (d, 8 H, J = 2 Hz), 5.26 (s, 8 H), 5.12 (s, 16 H), 5.06 (s,
34 H), –ꢀ.8ꢀ (s, 4 H); 13C NMR (CDCl3, 125 MHz) δ ppm =
191.7, 160.3, 159.8, 158.5, 143.5, 139.6, 135.9, 135.7, 1ꢀ9.9,
1ꢀ7.4, 113.ꢀ, 106.7, 106.5, 101.6, 70.8, 69.9, 69.3. MS (MAL-
DI-TOF) m/z: 4033.4 (M + H+). Calcd 4031.3.
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Acknowledgments. This research was supported by the Israel
Science Foundation (ꢀꢀ7/05) and the Edmund Safra Founda-
tion.
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