European Polymer Journal 45 (2009) 31963209

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European Polymer Journal

journal homepage: www.elsevier.com/locate/europolj

Convergent synthesis of dendrimers based on 1,3,3-trisubstituted

2-oxindoles
A. Vandendriessche a, J. Thomas a, C. Van Oosterwijck a, J. Huybrechts b,1, B. Dervaux c,
S. Dhollander c, F. Du Prez c, W. Dehaen a, M. Smet a,*
a
Department of Chemistry, University of Leuven, Celestijnenlaan 200F, B-3001 Leuven, Belgium
b
Department of Biology, University of Leuven, Naamsestraat 59, B-3000 Leuven, Belgium
c
Department of Organic Chemistry, Ghent University, Krijgslaan 281 (S4-bis), B-9000 Ghent, Belgium

a r t i c l e i n f o a b s t r a c t

Article history: Dendrons and dendrimers were convergently prepared using an isatin as AB2 monomer by
Received 14 May 2009 superelectrophilic arylation in triuoromethanesulfonic acid. This strategy has the advan-
Received in revised form 3 August 2009 tage that incomplete reactions of the AB2 monomer are minimized, thus simplifying
Accepted 4 August 2009
purication. As the obtained dendrons/dendrimers are analogues of the hyperbranched
Available online 11 August 2009
polymers with a degree of branching of 100% developed earlier in our group, an opportu-
nity is created to compare the latter with their structurally perfect counterparts.
Keywords:
2009 Elsevier Ltd. All rights reserved.
Dendrimers
Convergent synthesis
Isatin
Superelectrophilic substitution

1. Introduction
Dendrimers have attracted a lot of attention during the
last two decades. They have a perfectly controlled, highly
branched, monodisperse structure and nd applications
in numerous elds such as catalysis, biosensors, MRI, as
endo- and exoreceptors, drug delivery systems and unimo-
lecular micelles [17].
Here we report the rst application of the potential
superelectrophilicity of isatin (a heterocyclic 1,2-dicarbonyl
compound) in the convergent synthesis of dendrimers.
It is well known that in superacidic environment isatin,
as a 1,2-diketone, gets doubly protonated and the resulting
superelectrophile condenses readily with aromatic hydro-
carbons to give exclusively 3,3-diaryloxindoles in high
yield. This is a result of the much higher reactivity of the
monoarylated intermediate compared to the reactivity of
* Corresponding author. Tel.: +32 16 32 7464; fax: +32 16 32 7990.
E-mail address: Mario.Smet@chem.kuleuven.be (M. Smet).
1
Fax: +32 16 32 3902.
the starting material and the reversibility of the rst aryla-
tion (Scheme 1) [8].
Based on this effect we previously synthesized hyper-
branched poly(arylene oxindole)s with a degree of branch-
ing of 100% [9,10]. Even though both these hyperbranched
polymers and the target analogous dendrimers would have
a poly(arylene oxindole) backbone consisting of exclu-
sively dendritic and terminal units, there are some impor-
tant differences to consider. Dendrimers are monodisperse
and have a spherical structure whereas hyperbranched
polymers do not have such a perfectly controlled structure,
which is apparent on the basis of their relatively high dis-
persity of molar mass and topology. Given that 100%
branched hyperbranched polymers are still poorly studied
in literature, having at hand the analogue dendrimers of
the fully branched hyperbranched poly(arylene oxindole)s
developed in our group could offer the opportunity to
study their differences in more detail. This is a rst issue
that triggered our interest in the dendrimers described
below.
On the other hand, the convergent synthesis of dendri-
mers is often complicated by purication problems caused

0014-3057/$ - see front matter 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.eurpolymj.2009.08.001
 A. Vandendriessche et al. / European Polymer Journal 45 (2009) 31963209
X X
O
R R
R
O O
N CF3SO3H
CF3SO3H
R'
Scheme 1. Superelectrophilic arylation of isatin.
by the presence of only partly reacted protected ABn mono-
mer in the reaction mixture. In convergent dendrimer syn-
thesis, dendrons are prepared rst, starting from the
periphery, and attached to the core in the nal step of
the sequence, resulting in a dendrimer. Although this
methodology has many advantages as compared to the
divergent strategy, the synthesis can be complicated al-
ready from relatively low generations on due to incom-
plete reaction of the ABn monomer with the activated
dendrons in the propagation step due to steric hindrance.
If the presence of the byproduct resulting from this partial
reaction could be avoided, this would simplify the purica-
tion to a signicant extent. Therefore, we reasoned that the
superelectrophilic arylation of isatin, used as the AB2
monomer, could be an attractive strategy for dendrimer
growth as in this case complete reaction of both B func-
tionalities is strongly favoured and hence less byproducts
should be expected.
As will be discussed in more detail, the commercially
available 5-bromoisatin was used as AB2 monomer to con-
struct the dendrons.
2. Experimental part
All chemicals were purchased from ACROS Organics or
SigmaAldrich and used as received without further puri-
cation. NMR spectra were recorded on a Bruker Avance 300
(300 and 75 MHz) or a Bruker Avance 400 (400 and
100 MHz). Gel permeation chromatography (GPC) was per-
formed with a Shimadzu apparatus (UV and RI detection)
with a PLgel D column (Polymer Laboratories) and tetrahy-
drofuran as the eluent at 30 C and 1 ml/min calibrated
with linear polystyrene standards.
The MALDI-TOF MS spectra for compounds 10, 12, 21,
22, 24 and 25 were recorded on a Reex IV instrument
(Bruker Daltonic, Bremen, Germany), equipped with a
nitrogen laser (337 nm) and pulsed ion extraction acces-
sory. The instrument was operated in the positive ion,
reectron mode and calibrated using a standard peptide
mixture containing angiotensin II (1045.54 Da), angioten-
sin I (1295.68 Da), substance P (1346.73 Da), bombesin
(1618.82 Da), ACTH clip 117 (2092.08 Da) and ACTH clip
1839 (2464.19 Da) (Bruker Daltonic). The samples were
dissolved in tetrahydrofuran. 1 ll of this sample solution
was transferred to a ground steel target plate, mixed with
0.5 ll of a saturated solution of a-cyano-4-hydroxycin-
namic acid (in tetrahydrofuran) and air-dried.
The MALDI-TOF MS for compounds 7, 8, 9, 11, 23, 26
were recorded on an Applied Biosystems Voyager DE STR
3197
X X
X
OH
N
N
R'
R'
MALDI-TOF spectrometer equipped with 2-m linear and
3-m reector ight tubes and a 337-nm nitrogen laser
(3-ns pulse). All mass spectra were obtained with an
accelerating potential of 20 kV in positive ion mode and
in linear and/or reector mode. Trans-2-[3-(4-tert-butyl-
phenyl)-2-methyl-2-propenylidene]malononitrile (BMPM)
(20 mg/mL in THF) was used as a matrix, sodium iodide
(1 mg/mL in THF) was used as a cationating agent, and
polymer samples were dissolved in THF (12 mg/mL).
The ratio of these three solutions on the sample
plate was 2/1/1. A poly(ethylene oxide) standard (Mn =
10000 g/mol) was used for calibration. All data were pro-
cessed using the Data Explorer (Applied Biosystems).
2.1. Synthesis of 3,3-bis(4-chlorophenyl)-5-bromo-2-indolone
(= B-terminated non-activated dendron of the 1st generation)
(3)
A mixture of 5-bromoisatin (1) (12.0 g, 53.1 mmol) and
chlorobenzene (2) (39.8 g, 0.354 mol) in triuoromethane-
sulfonic acid (triic acid) (16 ml) was stirred for 24 h at
room temperature. After pouring into ice, the mixture
was extracted with CH2Cl2 (3  50 ml), washed with a sat-
urated solution of NaHCO3, dried over MgSO4 and concen-
trated under reduced pressure. The residue was puried by
column chromatography (silica gel and CH2Cl2/EtOAc (95/
5) as eluent) to obtain the B-terminated non-activated
dendron of the 1st generation 3 (15.4 g, 68%).
MS (Cl): m/z = 434 (MH+). Mp: 125 C. 1H NMR
(400 MHz, CDCl3): d = 9.55 (s, 1H, NH), 7.36 (dd, 1H,
3
J = 8.4 Hz, 4J = 2.0 Hz, 6-H isatin), 7.28 (d, 4H, 3J = 8.4 Hz,
m-H to Cl), 7.25 (d, 1H, 4J = 2.0 Hz, 4-H isatin), 7.16 (d,
4H, 3J = 8.4 Hz, o-H to Cl), 6.82 (d, 1H, 3J = 8.2 Hz, 4-H isat-
in). 13C NMR (100 MHz, CDCl3): d = 179.0, 139.1, 139.0,
134.7, 134.1, 131.8, 129.6, 129.0, 126.4, 115.8, 112.2, 62.2.
2.2. Synthesis of 4-methyl-40 -phenoxybenzophenone (4)
p-Toluoyl chloride (17.8 ml; 135 mmol) was added to a
suspension of diphenyl ether (22.0 9; 135 mmol) and alu-
minium trichloride (20.8 g; 156 mmol) in dichloromethane
(25 ml). After heating at reux temperature for 10 min the
mixture was poured onto a mixture of ice (200 ml) and
concentrated HCl (20 ml) and was extracted with dichloro-
methane (3  200 ml). The combined organic phases were
washed with a saturated solution of NaHCO3, dried over
magnesium sulfate and concentrated under reduced pres-
sure. The pure compound was obtained by washing with
3198 A. Vandendriessche et al. / European Polymer Journal 45 (2009) 31963209
petroleum ether, ltering and drying in vacuum. (27.7 g,
71%).
MS (CI): m/z = 289 (MH+). Mp: 7880 C. 1H NMR
(400 MHz, CDCl3): d = 7.80 (d, 2H, 3J = 8.8 Hz, m-H to
OPh), 7.70 (d, 2H, 3J = 8.0 Hz, m-H to CH3), 7.39 (t, 2H,
3
J = 7.7 Hz, m-H to OPhCO), 7.27 (d, 2H, 3J = 8.1 Hz, o-H to
CH3), 7.18 (t, 1H, 3J = 5.6 Hz, p-H to OPhCO), 7.09 (d, 2H,
3
J = 7.3 Hz, o-H to OPhCO), 7.02 (d, 2H, 3J = 8.8 Hz, o-H to
OPh), 2.43 (s, 3H, CH3). 13C NMR (100 MHz, CDCl3):
d = 195.2, 161.4, 155.7, 142.9, 135.2, 132.3, 130.1, 130.0,
128.9, 124.5, 120.1, 117.2, 21.6.
2.3. Synthesis of 4-bromomethyl-40 -phenoxybenzophenone
(5)
A solution of methyl compound 4 (18.1 g; 62.5 mmol),
N-bromosuccinimide (11.1 g; 62.5 mmol) and benzoyl per-
oxide (10 mg) in tetrachloromethane (80 ml) was heated at
reux temperature during 5 h under argon atmosphere.
The tetrachloromethane was evaporated under reduced
pressure and the residue was extracted with dichloro-
methane (3  150 ml). The combined organic phases were
washed with a saturated solution of NaHCO3, dried over
magnesium sulfate and the solvent was evaporated under
reduced pressure. Bromide 5 was used in the next reaction
without further purication. (18.0 g, 79%).
MS (CI): m/z = 368 (MH+). Mp: 8587 C. 1H NMR
(300 MHz, CDCl3): d = 7.81 (d, 2H, 3J = 9.1 Hz, m-H to
OPh), 7.76 (d, 2H, 3J = 7.3 Hz, m-H to CH2), 7.50 (d, 2H,
3
J = 7.3 Hz, o-H to CH2), 7.097.44 (m, 5H, m-H to OPhCO,
p-H to OPhCO, o-H to OPhCO), 7.03 (d, 2H, 3J = 9.1 Hz, o-H
to PhCOPh), 4.54 (s, 2H, CH2).
General procedure for the synthesis of B-terminated
activated dendrons, illustrated for 3,3-bis(4-chloro-
phenyl)-5-bromo-1-((4-phenoxybenzoyl)benzyl)-2-indo-
lone (= B-terminated activated dendron of the 1st
generation) (G1) 6.
A mixture of compound 3 (15.0 g; 34.8 mmol), bromide
5 (12.9 g; 34.8 mmol) and potassium carbonate (4.80 g;
34.8 mmol) in DMF (100 ml) was stirred for 18 h at 60 C.
The reaction mixture was extracted with EtOAc (3 
200 ml) and the combined organic layers were dried with
MgSO4 and evaporated under vacuum. The residue was
further puried by column chromatography (silica gel
and CH2Cl2 as eluent) to obtain the B-terminated activated
dendron of the 1st generation (G1) (19.1 g, 76%).
MS (ESI): m/z = 720 (MH+). 1H NMR (300 MHz, CDCl3):
d = 7.74 (m, 4H, m-H to OPh + m-H to CH2), 7.37 (m, 4H,
m-H to OPhCO + 4-H isatin + 6-H isatin), 7.29 (m, 6H, o-H
to CH2 + m-H to Cl), 7.22 (m, 1H, p-H to OPhCO), 7.18 (m,
4H, o-H to Cl), 7.04 (m, 4H, o-H to OPhCO + o-H to OPh),
6.69 (d, 1H, 3J = 8.8 Hz, 7-H isatin), 5.04 (s, 2H, CH2). 13C
NMR (75 MHz, CDCl3): d = 194.6, 176.4, 161.8, 155.3,
140.7, 139.2, 139.1, 137.6, 134.1, 133.9, 132.4, 131.8,
131.5, 130.5, 130.0, 129.6, 129.0, 126.8, 124.6, 120.2,
117.1, 116.1, 111.2, 61.5, 43.9.
General procedure for the synthesis of B-terminated
non-activated dendrons, illustrated for the B-terminated
non-activated dendron of the 2nd generation 7.
A mixture of compound 6 (15.4 g; 21.4 mmol) and 5-
bromoisatin (1) (2.99 g; 13.3 mmol) in triic acid was stir-
red for 24 h at 60 C. After pouring into ice, the mixture
was extracted with CH2Cl2 (3  50 ml), washed with a sat-
urated solution of NaHCO3, dried over MgSO4 and concen-
trated under reduced pressure. The residue was puried by
column chromatography (silica gel and CH2Cl2/EtOAc (95/
5) as eluent) to obtain the B-terminated non-activated
dendron of the 2nd generation. (16.5 g, 94%).
MALDI-TOF MS: m/z = 1669.7. GPC: Mn = 1.4  103 g/
mol, Mw/Mn = 1.07. 1H NMR (300 MHz, CDCl3): d = 9.18 (s,
1H, NH), 7.74 (m, 8H, m-H to CH2 + m-H to OPhoxindole),
7.33 (m, 22H, 4-H oxindolePhO + 4-H oxindolePhCl + 6-H
oxindolePhO + 6-H oxindolePhCl + m-H to Cl + o-H to oxin-
dole + o-H to CH2), 7.17 (d, 8H, 3J = 9.2 Hz, o-H to Cl), 7.04
(m, 8H, o-H to OPhCO + o-H to OPhoxindole), 6.87 (d, 1H,
3
J = 8.2 Hz, 7-H oxindolePhO), 6.69 (d, 2H, 3J = 9.2 Hz, 7-H
oxindolePhCl), 5.04 (s, 4H, CH2). 13C NMR (75 MHz, CDCl3):
d = 194.7, 179.1, 176.5, 161.1, 155.2, 140.7, 139.4, 139.2,
137.5, 136.9, 135.3, 134.1, 133.9, 132.4, 131.9, 131.8,
131.6, 130.5, 130.0, 129.6, 129.2, 129.0, 126.8, 120.0,
117.6, 116.2, 115.6, 112.0, 111.2, 73.9, 62.0, 61.5, 43.9.
2.4. Synthesis of B-terminated activated dendron of the 2nd
generation (G2) 8
This was obtained by the general procedure for the syn-
thesis of B-terminated activated dendrons in a yield of 82%.
MALDI-TOF MS: m/z = 1956.2. GPC: Mn = 1.6  103 g/
mol, Mw/Mn = 1.08. 1H NMR (300 MHz, CDCl3): d = 7.75
(m, 12H, m-H to CH2 + m-H to OPhoxindole), 7.34 (m,
26H, 4-H oxindolePhO + 4-H oxindolePhCl + 6-H oxindole-
PhO + 6-H oxindolePhCl + m-H to Cl + o-H to oxindole + o-
H to CH2 + m-H to OPhCO), 7.22 (m, 1H, p-H to OPhCO),
7.17 (m, 8H, o-H to Cl), 7.07 (m, 12H, o-H to OPhCO + o-H
to OPhoxindole), 6.69 (m, 3H, 7-H oxindolePhO + 7-H oxi-
ndolePhCl), 5.07 (s, 2H, CH2oxindolePhO), 5.04 (s, 4H,
CH2oxindolePhCl). 13C NMR (75 MHz, CDCl3): d = 194.6,
177.0, 176.5, 161.7, 161.1, 155.2, 140.7, 139.4, 139.1,
137.5, 136.8, 135.2, 134.1, 133.9, 132.6, 131.9, 131.8,
131.5, 130.5, 130.0, 129.6, 129.0, 128.8, 126.8, 120.0,
117.6, 116.2, 115.6, 112.0, 111.2, 61.6, 61.4, 43.9.
2.5. Synthesis of B-terminated non-activated dendron of the
3th generation 9
This was obtained by the general procedure for the syn-
thesis of B-terminated non-activated dendrons in a yield of
86%.
MALDI-TOF MS: m/z = 4097.1. GPC: Mn = 3.7  103
g/mol, Mw/Mn = 1.06. 1H NMR (300 MHz, CDCl3): d = 8.22
(s, 1H, NH), 7.74 (m, 24H, m-H to CH2 + m-H to OPhoxin-
dole), 7.33 (m, 54H, 4-H oxindolePhO + 4-H oxi-
ndolePhCl + 6-H oxindolePhO + 6-H oxindolePhCl + m-H
to Cl + o-H to dendritic oxindole + o-H to CH2), 7.16 (d,
16H, 3J = 9.2 Hz, o-H to Cl), 7.04 (m, 24H, o-H to OPh-
CO + o-H to OPhoxindole), 6.84 (d, 1H, 3J = 8.2 Hz, 7-H
oxindolePhO), 6.69 (d, 6H, 3J = 9.2 Hz, 7-H oxindolePhCl),
5.07 (s, 4H, CH2oxindolePhO), 5.04 (s, 8H, CH2oxi-
ndolePhCl). 13C NMR (75 MHz, CDCl3): d = 194.6, 178.5,
177.0, 176.4, 161.1, 161.0, 155.3, 155.1, 140.8, 140.7,
139.5, 139.3, 139.1, 137.4, 136.9, 134.6, 134.0, 133.9,
132.4, 132.0, 131.7, 131.5, 130.5, 130.0, 129.6, 129.0,
 A. Vandendriessche et al. / European Polymer Journal 45 (2009) 31963209
126.8, 126.8, 120.0, 117.6, 117.1, 116.1, 111.1, 61.9, 61.5,
43.9.
2.6. Synthesis of B-terminated activated dendron of the 3th
generation (G3) 10
This was obtained by the general procedure for the syn-
thesis of B-terminated activated dendrons in a yield of 84%.
MALDI-TOF MS: m/z = 4381.5. GPC: Mn = 3.9  103 g/
mol, Mw/Mn = 1.05. 1H NMR (300 MHz, CDCl3): d = 7.74
(m, 28H, m-H to CH2 + m-H to OPhoxindole), 7.32 (m,
59H, 4-H oxindolePhO + 4-H oxindolePhCl + 6-H oxindole-
PhO + 6-H oxindolePhCl + m-H to Cl + o-H to oxindole + o-
H to CH2 + m-H to OPhCO), 7.20 (m, 1H, p-H to OPhCO),
7.16 (m, 16H, o-H to Cl), 7.04 (m, 28H, o-H to OPhCO + o-
H to OPhoxindole), 6.69 (m, 7H, 7-H oxindolePhO + 7-H
oxindolePhCl), 5.07 (s, 6H, CH2oxindolePhO), 5.03 (s, 8H,
CH2oxindolePhCl). 13C NMR (75 MHz, CDCl3): d = 194.5,
177.0, 176.4, 161.7, 161.0, 155.3, 140.8, 140.7, 139.5,
139.3, 139.1, 137.5, 136.9, 134.6, 134.0, 133.9, 132.3,
132.0, 131.7, 131.5, 130.4, 130.0, 129.9, 129.5, 129.0,
126.9, 126.8, 124.6, 120.0, 117.6, 117.1, 116.1, 111.1,
61.5, 43.9.
2.7. Synthesis of B-terminated non-activated dendron of the
4th generation 11
This was obtained by the general procedure for the syn-
thesis of B-terminated non-activated dendrons in a yield of
71%.
MALDI-TOF MS: m/z = 8956.2. GPC: Mn = 7.6  103
g/mol, Mw/Mn = 1.07. 1H NMR (300 MHz, CDCl3): d = 8.14
(s, 1H, NH), 7.66 (m, 56H, m-H to CH2 + m-H to
OPhoxindole), 7.23 (m, 118H, 4-H oxindolePhO + 4-H oxi-
ndolePhCl + 6-H oxindolePhO + 6-H oxindolePhCl + m-H
to Cl + o-H to dendritic oxindole + o-H to CH2), 7.08 (d,
32H, 3J = 9.2 Hz, o-H to Cl), 6.96 (m, 56H, o-H to OPh-
CO + o-H to OPhoxindole), 6.72 (d, 1H, 3J = 8.2 Hz, 7-H
oxindolePhO), 6.61 (d, 14H, 3J = 9.2 Hz, 7-H oxindolePhCl),
4.99 (s, 12H, CH2oxindolePhO), 4.95 (s, 16H, CH2oxi-
ndolePhCl). 13C NMR (75 MHz, CDCl3): d = 194.6, 177.0,
176.4, 161.0, 155.3, 140.8, 140.7, 139.5, 139.3, 139.1,
137.5, 136.9, 134.6, 134.0, 133.9, 132.4, 132.0, 131.7,
130.5, 130.0, 129.9, 129.6, 129.0, 126.9, 126.8, 120.0,
117.6, 117.1, 116.1, 111.2, 61.5, 43.9.
2.8. Synthesis of B-terminated activated dendron of the 4th
generation 12
This was obtained by the general procedure for the syn-
thesis of B-terminated activated dendrons in a yield of 78%.
MALDI-TOF MS: m/z = 9241.7. GPC: Mn = 7.6  103 g/
mol, Mw/Mn = 1.07. 1H NMR (300 MHz, CDCl3): d = 7.73
(m, 60H, m-H to CH2 + m-H to OPhoxindole), 7.33 (m,
123H, 4-H oxindolePhO + 4-H oxindolePhCl + 6-H oxindo-
lePhO + 6-H oxindolePhCl + m-H to Cl + o-H to oxindole +
o-H to CH2 + m-H to OPhCO), 7.15 (m, 33H, o-H to Cl +
p-H to OPhCO), 7.03 (m, 60H, o-H to OPhCO + o-H to
OPhoxindole), 6.69 (m, 15H, 7-H oxindolePhO + 7-H oxi-
ndolePhCl), 5.06 (s, 14H, CH2oxindolePhO), 5.02 (s, 16H,
CH2oxindolePhCl). 13C NMR (75 MHz, CDCl3): d = 194.5,
3199
177.0, 176.4, 161.0, 155.3, 140.8, 140.7, 139.5, 139.3,
139.1, 137.5, 136.9, 134.6, 134.0, 133.9, 132.4, 132.0,
131.7, 130.5, 130.0, 129.9, 129.6, 129.0, 126.9, 126.8,
120.1, 120.0, 117.6, 117.1, 116.1, 111.2, 61.6, 43.9.
2.9. Synthesis of the B4 core 14
A mixture of bisbromide 13 (1.00 g, 3.78 mmol), 5-
bromoisatin (2.57 g, 11.3 mmol) and K2CO3 (1.57 g,
11.3 mmol) in DMF (20 ml) was stirred for 6 h at 50 C.
The solvent was evaporated and extracted with ethyl ace-
tate (3  50 ml). The combined organic layers were dried
over MgSO4 and concentrated under reduced pressure.
Pure compound 14 was obtained as an orange solid after
column chromatographic purication (silica, CH2Cl2/EtOAc
(9/1) as eluent). (Yield: 86%).
MS (CI) m/z = 555 (MH+). Mp: 330 C. 1H NMR (300 MHz,
CDCl3): d = 7.72 (t, 4H, 4-H isatin + 6-H isatin), 7.38 (d, 4H,
o-H to CH2), 6.90 (d, 2H, 7-H isatin), 4.88 (s, 4H, CH2).
2.10. Synthesis of the B6 cores
For the synthesis of 1,3,5-tris(4-uorobenzoyl)benzene
[11] (17) and 1,3,5-tris(4-hydroxybenzoyl)benzene [12]
(18) literature procedures were followed.
2.11. Synthesis of 5-bromo-N-(3-bromopropyl)-isatin 19
1,3-Dibromopropane (17.7 ml, 0.170 mol), 5-bromoi-
satin (3.84 g, 0.0170 mol) and K2CO3 (2.93 g, 0.0212 mol)
were stirred in DMF for 24 h at 40 C. The solvent was
evaporated under reduced pressure and the mixture
was extracted with CH2Cl2 (3  100 ml). Pure compound
was obtained after column chromatographic purication
(silica gel and CH2Cl2/petroleum ether (80/20) as eluent).
(Yield: 4.11 g, 51%).
MS (CI: m/z = 348 (MH+). Mp: 155 C. 1H NMR (300 MHz,
CDCl3): d = 7.73 (m, 2H, 4-H isatin + 6-H isatin), 6,97 (d, 1H,
7-H isatin), 3.90 (t, 2H, NCH2CH2CH2Br), 3.46 (t, 2H,
NCH2CH2CH2Br), 2.27 (m, 2H, NCH2CH2CH2Br). 13C NMR
(75 MHz, CDCl3): d = 182.0, 157.7, 149.5, 140.8, 128.4,
118.9, 116.8, 111.9, 39.1, 30.2, 30.1.
2.12. Synthesis of B6 core 20
Trihydroxy compound 17 (25.0 g, 0.57 mmol), 5-bro-
mo-N-bromopropyl-isatin 19 (1.00 g, 2.85 mmol) and
K2CO3 (3.50 g, 25.0 mmol) were stirred in DMF (20 ml)
for 48 h at 80 C. The reaction mixture was poured into a
waterHCl mixture (pH = 6). The red precipitate was l-
tered and puried by column chromatography (silica gel
and CH2Cl2/EtOAc (70/30) as eluent) to obtain the B6 core
(4.04 g, 60%).
MS (ESI): m/z = 1238 (MH+). Mp: 111 C. 1H NMR
(300 MHz, CDCl3): d = 8.27 (s, 3H, C6H3(CO)3), 7.84 (d, 6H,
o-H to C6H3(CO)3), 7.70 (d, 3H, 4-H isatin), 7.64 (dd, 3H,
6-H isatin), 6.94 (d, 6H, m-H to PhCO), 6.87 (d, 3H, 7-H
isatin), 4.13 (t, 6H, NCH2CH2CH2Br), 3.96 (t, 6H,
NCH2CH2CH2Br), 2.24 (m, 6H, NCH2CH2CH2Br). 13C NMR
(75 MHz, CDCl3): d = 194.0, 182.6, 162.9, 158.0, 150.0,
3200 A. Vandendriessche et al. / European Polymer Journal 45 (2009) 31963209
141.0, 139.0, 133.6, 133.1, 129.9, 128.6, 119.1, 117.0, 114.7,
114.3, 112.2, 65.7, 37.9, 27.4.
2.13. General procedure for the synthesis of the dendrimers,
illustrated for dendrimer B4G1 (21)
The activated dendron of the rst generation 6 (0.50 g,
0.69 mmol) and B4 core 14 (0.090 g, 0.16 mmol) were stir-
red in triic acid (3 ml) for 24 h at 60 C. After pouring the
solution into water, the precipitate was extracted with
CH2Cl2 (3  30 ml). The dendrimer of the rst generation
was obtained in a pure form after column chromatography
(silica gel and CH2Cl2/EtOAc (98/2) as eluent). (0.31 g,
yield: 85%).
MALDI-TOF MS: m/z = 3419.8. GPC: Mn = 2.9  103 g/
mol, Mw/Mn = 1.06. 1H NMR (300 MHz, CDCl3): d = 7.76
(m, 16H, m-H to OPh + m-H to CH2), 7.32 (m, 44H, m-H
to OPhCO + 4-H isatin dendron + 6-H isatin dendron, 4-H
isatin core + 6-H isatin core, o-H to CH2 + m-H to Cl), 7.20
(m, 20H, o-H to Cl + o-H to CH2 core), 7.05 (m, 16H, o-H
to OPhCO + o-H to OPh), 6.69 (d, 6H, 3J = 8.8 Hz, 7-H isatin
dendron + 7-H isatin core), 5.05 (s, 8H, CH2 dendron), 4.97
(s, 4H, CH2 core). 13C NMR (100 MHz, CDCl3): d = 194.6,
177.0, 176.4, 161.0, 155.2, 140.9, 140.7, 139.4, 139.1,
137.5, 137.0, 134.1, 133.9, 132.4, 132.0, 131.7, 130.5,
130.0, 129.6, 129.0, 127.7, 126.8, 120.0, 117.6, 116.2,
111.2, 61.5, 43.9.
2.14. Synthesis of dendrimer B4G2 (22)
This was obtained by the general procedure for the syn-
thesis of the dendrimers, mentioned above in a yield of
81%. MALDI-TOF MS: m/z = 8197.4. GPC: Mn = 6.7  103 g/
mol, Mw/Mn = 1.07. 1H NMR (300 MHz, CDCl3): d = 7.74
(m, 48H, m-H to OPh + m-H to CH2), 7.33 (m, 104H, m-H
to OPhCO + 4-H isatin dendron + 6-H isatin dendron + 4-H
isatin core + 6-H isatin core, o-H to CH2 + m-H to Cl + o-H
to CH2 core), 7.18 (m, 32H, o-H to Cl), 7.05 (d, 48H, o-H
to OPhCO + o-H to OPh), 6.70 (d, 14H, 3J(H-H) = 8.8 Hz, 7-
H isatin dendron + 7-H isatin core), 5.08 (s, 8H, CH2oxindo-
lePhO), 5.04 (s, 16H, CH2oxindolePhCl), 4.95 (s, 4H, CH2
core). 13C NMR (100 MHz, CDCl3): d = 194.6, 177.0, 176.4,
161.0, 155.2, 140.8, 140.7, 139.3, 139.1, 137.5, 136.9,
134.0, 133.9, 132.4, 132.0, 131.6, 130.5, 130.0, 129.6,
129.0, 127.7, 126.8, 120.0, 117.6, 116.1, 111.1, 61.5, 43.8.
2.15. Synthesis of dendrimer B4G3 (23)
This was obtained by the general procedure for the syn-
thesis of the dendrimers, mentioned above in a yield of
80%. GPC: Mn = 1.0 104 g/mol, Mw/Mn = 1.16. 1H NMR
(300 MHz, CDCl3): d = 7.67 (m, 112H, m-H to OPh + m-H
to CH2), 7.24 (m, 240H, m-H to OPhCO + 4-H isatin den-
dron + 6-H isatin dendron + 4-H isatin core + 6-H isatin
core, o-H to CH2 + m-H to Cl + o-H to CH2 core), 7.07 (d,
64H, p-H to OPhCO + o-H to Cl), 6.96 (d, 112H, o-H to OPh-
CO + o-H to OPh), 6.60 (m, 30H, 7-H isatin dendron + 7-H
isatin core), 4.98 (s, 24H, CH2oxindolePhO), 4.95 (s, 32H,
CH2oxindolePhCl), 4.75 (s, 4H, CH2 core). 13C NMR
(100 MHz, CDCl3): d = 194.5, 177.0, 176.4, 161.0, 155.3,
140.8, 140.7, 139.3, 139.1, 137.5, 136.9, 134.0, 133.9,
132.4, 132.0, 131.7, 130.5, 130.0, 129.6, 129.0, 126.8,
120.0, 117.6, 116.1, 111.2, 61.5, 43.9.
2.16. Synthesis of dendrimer B6G1 (24)
This was obtained by the general procedure for the syn-
thesis of the dendrimers, mentioned above in a yield of
76%. MALDI-TOF MS: m/z = 5525.1. GPC: Mn = 4.6  103 g/
mol, Mw/Mn = 1.04. 1H NMR (300 MHz, CDCl3): d = 8.19 (s,
3H, C6H3(CO)3 core), 7.76 (m, 36H, m-H to OPh + m-H to
CH2 + 4-H isatin core + 6-H isatin core + o-H to C6H3(CO)3
core), 7.30 (m, 60H, m-H to OPhCO + 4-H isatin den-
drons + 6-H isatin dendrons, o-H to CH2 + m-H to Cl), 7.15
(m, 24H, o-H to Cl), 7.01 (m, 24H, o-H to OPhCO + o-H to
OPh), 6.80 (m, 9H, 7-H isatin core + m-H to C6H3(CO)3
core), 6.67 (m, 6H, 7-H isatin dendrons), 5.03 (s,
12H, CH2oxindolePhCl), 4.04 (m, 12H, NCH2CH2CH2Br +
NCH2CH2CH2Br), 2.18 (m, 6H, NCH2CH2CH2Br). 13C NMR
(100 MHz, CDCl3): d = 194.6, 176.5, 161.1, 155.3, 140.8,
139.4, 139.2, 137.6, 137.0, 134.1, 132.4, 131.8, 130.5,
130.0, 129.6, 129.0, 128.8, 126.9, 120.0, 117.6, 116.2,
111.2, 61.6, 61.4, 43.9.
2.17. Synthesis of dendrimer B6G2 (25)
This was obtained by the general procedure for the syn-
thesis of the dendrimers, mentioned above in a yield 72%.
MALDI-TOF MS: m/z = 12 809.1. GPC: Mn = 9.4  103 g/
mol, Mw/Mn = 1.07. 1H NMR (300 MHz, CDCl3): d = 8.02 (s,
3H, C6H3(CO)3 core), 7.68 (m, 72H, m-H to OPh + m-H to
CH2 + 4-H isatin core + 6-H isatin core + o-H to C6H3(CO)3
core), 7.23 (m, 168H, m-H to OPhCO + 4-H isatin den-
drons + 6-H isatin dendrons, o-H to CH2 + m-H to Cl), 7.08
(m, 48H, o-H to Cl), 6.97 (m, 72H, o-H to OPhCO + o-H to
OPh), 6.60 (m, 9H, 7-H isatin core + m-H to PhCO core),
6.61 (m, 18H, 7-H isatin dendrons), 4.99 (s, 12H, CH2oxin-
dolePhO), 4.96 (s, 24H, CH2oxindolePhCl), 4.05 (m, 12H,
NCH2CH2CH2Br + NCH2CH2CH2Br), 2.24 (m, 6H, NCH2-
CH2CH2Br). 13C NMR (100 MHz, CDCl3): d = 194.6, 177.0,
176.4, 161.0, 155.3, 155.1, 140.7, 139.3, 139.1, 137.4,
136.9, 134.5, 134.0, 133.9, 132.4, 131.9, 131.8, 130.5,
129.9, 129.5, 129.0, 126.8, 120.0, 117.6, 116.1, 116.1,
114.3, 111.1, 61.5, 43.8.
2.18. Synthesis of dendrimer B6G3 (26)
This was obtained by the general procedure for the syn-
thesis of the dendrimers, mentioned above in a yield of
66%. MALDI-TOF MS: m/z = 27 370.0. GPC: Mn = 16 
103 g/mol, Mw/Mn = 1.10. 1H NMR (300 MHz, CDCl3):
d = 7.75 (m, 189H, C6H3(CO)3 core, m-H to OPh + m-H to
CH2 + 4-H isatin core + 6-H isatin core + o-H to C6H3(CO)3
core), 7.30 (m, 397H, m-H to OPhCO + 4-H isatin den-
drons + 6-H isatin dendrons, o-H to CH2 + m-H to Cl), 7.15
(m, 102H, o-H to Cl), 7.03 (m, 170H, o-H to OPhCO + o-H
to OPh), 6.60 (m, 9H, 7-H isatin core + m-H to PhCO core),
6.68 (m, 40H, 7-H isatin dendrons), 4.99 (s, 12H, CH2
oxindolePhO), 4.86 (s, 26H, CH2 oxindolePhCl), 4.05
(m, 12H, NCH2CH2CH2Br + NCH2CH2CH2Br), 2.24 (m,
6H, NCH2CH2CH2Br). 13C NMR (100 MHz, CDCl3): d =
194.6, 177.1, 176.4, 161.0, 155.3, 140.7, 139.4, 139.1,
 A. Vandendriessche et al. / European Polymer Journal 45 (2009) 31963209
137.5, 136.9, 134.6, 134.1, 133.9, 132.4, 131.9, 131.7, 130.5,
129.9, 129.5, 129.0, 126.8, 120.0, 117.6, 116.1, 116.1, 111.1,
61.5, 43.9.
3. Results and discussion
3.1. Synthesis
3.1.1. Synthesis of the 1,3,3-trisubstituted oxindole dendrons
To synthesize the target 1,3,3-trisubstituted oxindole
dendrons, the following iterative sequence was designed.
The actual propagation step involves the condensation of
the AB2 monomer 5-bromoisatin (1) in triuoromethanesul-
fonic acid with the appropriate phenoxy terminated den-
drons to yield the deactivated dendrons of one generation
higher. The relatively electron rich phenoxy substituent
functions as the activating group for the superelectrophilic
aromatic substitution. For the synthesis of the G1 deacti-
vated dendron 3 readily available chlorobenzene was used
in combination with the AB2 monomer. The resulting chlo-
rophenyl substituents were found to be inactive for further
condensation with isatin and hence function as appropriate
inert terminal groups. Dendrons 7, 9 and 11 were obtained in
high yield with good regioselectivity for para substitution of
the phenoxy unit [8]. The activation of these 3,3-diaryloxin-
doles is obtained by alkylation with 4-bromomethyl-40 -
phenoxybenzophenone (5) in basic conditions yielding the
activated dendrons 6, 8, 10 and 12, respectively. The
required alkylating agent 5 was readily prepared by bromin-
ation of 4-methyl-40 -phenoxybenzophenone (4). By repeti-
tion of these condensation and activation steps dendrons
up to the fourth generation were synthesized (Scheme 2).
It should be noted that although this sequence affords the
dendritic analogues of the hyperbranched poly(arylene
oxindole)s prepared earlier [9], the actual AB2 monomers
used are different. As the hyperbranched polymers synthesis
is a one step procedure, the phenoxy unit is already present
in the AB2 monomer as the A unit. To allow the step wise
dendrimer synthesis, however, the phenoxy unit is intro-
duced in the activation step and hence commercial 5-bro-
moisatin (1) can be used as the AB2 monomer directly in
the propagation step of the synthetic sequence, implying
that the 3-carbonyl function of isatin acts as the B2 function-
ality and the nucleophilic NH group as the A functionality.
The different generations of dendrons are abbreviated with
Gy with y referring to the corresponding generation. All the
dendrons were successfully puried by column chromatog-
raphy (silicagel) and obtained in good yield. They all show
good solubility in common organic solvents, such as CHCl3,
THF and CH2Cl2.
3.1.2. Synthesis of the B4 and B6 core
Two different oligofunctional cores based on isatin,
were synthesized in order to enable the attachment of
the dendrons by the same superelectrophilic aromatic sub-
stitution. The tetrafunctional core (B4 core, 14) was synthe-
sized by alkylation of 5-bromoisatin (1) with 1,4-
bis(bromomethyl)benzene (13) under basic conditions
(Scheme 3).
The synthesis of the hexafunctional core (B6) core is de-
picted in Scheme 4. The rst step is the Vilsmeier reaction
3201
of 4-uorobenzophenone (15) with DMF and POCl3 result-
ing in compound 16. Upon heating of the latter at reux
temperature in DMSO, structure 17 was formed and was
subsequently converted into the corresponding triphenol
18 [11,12]. Nucleophilic substitution of this phenol with
alkylated isatin 19 resulted in the desired core 20. The
alkylated isatin 19 was synthesized by alkylation of 5-bro-
moisatin with an excess of 1,3-dibromopropane under ba-
sic conditions.
The hexafunctional core 20 has some attractive fea-
tures. First of all is it easily recognizable in 1H NMR spec-
troscopy. The singlet at 8.02 ppm due to the protons of
the internal aromatic ring (C6H3(CO)3) can be clearly ob-
served well separated from the region where the dendrons
will absorb. The three COPh units introduced in the core
act as a spacer to avoid steric hindrance and hence can
be expected to increase the reactivity for the attachment
of the three isatin units. The propyl group not only further
decreases the steric barrier but its exibility also increases
the solubility of the resulting core. Furthermore we assume
that the alkyl chain is short enough to arrange the dendri-
mers into a globular conformation from relatively low gen-
erations on.
3.1.3. Synthesis of the dendrimers
The activated dendrons of the different generations
were coupled with the B4 and the B6 core 14 and 20,
respectively, by an acid catalyzed condensation reaction
in triuoromethanesulfonic acid. This reaction is depicted
in Scheme 5 for the activated dendron of the rst genera-
tion with the B6 core.
The rst three generations of dendrimers with the B6
and B4 core were successfully puried by column chroma-
tography and their corresponding yields are represented in
Table 1. The synthesis of the 4th generation dendrimers
needed a longer reaction time and a large excess of den-
drons to drive the reaction to completion since the separa-
tion of partially reacted side products from the desired
product was complex. However, the longer reaction time
resulted in some cross linked material for the 4th genera-
tion dendrimer, which can be easily removed by ltration.
The excess of dendrons used made the purication of unre-
acted dendron from the 4th generation dendrimer unsuc-
cessful while using a stoichiometric amount resulted in
structural defects. The different dendrimers are abbrevi-
ated with the formula BxGy with x the functionality of the
core and y the generation number.
3.2. Characterization
3.2.1. NMR spectroscopy
3.2.1.1. NMR spectra of the dendrons. Already from the sec-
ond generation on, the NMR spectra of the dendrons are
rather complex due to numerous overlapping peaks. More-
over, focussing on the proton on the N-atom of the non-
activated dendrons, which is not overlapping, is not
straightforward because this signal is not always visible.
Still, integration is a useful diagnostic tool for monitoring
the generation progress within a series of dendrons.
In Figs. 1 and 2 the 1H NMR spectra of the respectively
activated and non-activated dendron of the second
3202 A. Vandendriessche et al. / European Polymer Journal 45 (2009) 31963209

Cl O

Cl Br
O Cl 5 O
O O

N 2 N 4(4'phenoxybenzoyl)benzyl (PBB)
H H
Br Br K2CO3, DMF, 60 C
RT, CF 3SO3H
1 68% 3 76%

R
Cl
N O Cl

O
O Br
Br
Cl N
O O
O O
Cl
O 1
N 60 C, CF3SO3H
O Br
Br 6 94%
N
G1 G2 O
Cl

Cl

7R=H
5, K2CO3, DMF

8 R = PBB 82%

1 1
G3 G4
60 C, CF3SO3H 60 C, CF3SO3H
86% 9R=H 5, K2CO3 71% 11 R = H
5, K2CO3, DMF
DMF
10 R = PBB 84% 78%
12 R = PBB

Scheme 2. A schematic overview of the synthesis of the dendrons up to the fourth generation (G4).

Br

Br O N
O
Br K2CO3 O
+ O
N DMF, 50C O
H
86%
Br N O
13 1 14

Br
Scheme 3. Synthesis of the B4 core 14.
 A. Vandendriessche et al. / European Polymer Journal 45 (2009) 31963209 3203

O
F
O Cl O
POCl3 CHO DMSO
DMF, 75 C reflux
F F 22% O
15 16
F 17
F

O
O Br
OH O
O N
KOH, H 2O Br
19
DMSO, RT
O K2CO3, DMF, 40 C
96%
51%
HO

HO 18

O O

Br O
N O O N O

O O
O
O O
Br
O N
20

Br

Scheme 4. Synthesis of the B6 core.

generation are displayed. A few characteristic differences
allow a clear distinction between the spectra of the acti-
vated and the non-activated dendron. In the non-activated
dendron 7 two peaks correspond to the 7-H of the different
oxindole residues: one doublet at 6.67 ppm and one at
6.88 ppm. The latter peak can be assigned to the focal oxin-
dole group that has a free NH group and has indeed an
integration value of one. The former doublet corresponds
to the terminal chlorophenyl substituted oxindole groups.
As expected it has an integration value of two. In the 1H
NMR spectrum of the activated dendron these two peaks
are no longer separated but overlap with each other at
6.70 ppm and have an integration value of three. This is be-
cause of the different chemical environment of the alkyl-
ated and non-alkylated isatins.
Another element to distinguish the 1H NMR spectra of
the alkylated and non-alkylated dendrons is based on the
relative integration between the methylene protons and,
for example, the protons in ortho position to the chlorine
substituent (peak at 7.17 ppm). After alkylation, the num-
ber of methylene protons raises with two whereas the
number of protons ortho to the chlorine atom remains
the same.
Considering the relative integration of the methylene
protons with respect to the combined signals of the pro-
tons ortho to OPhCO and ortho to OPhoxindole (peak at
7.04 ppm) we nd that the integration of the latter peak in-
creases with four after alkylation while the number of
methylene protons only raises with two. Checking these
integration values is also an efcient tool to determine
whether the activation was successful or not.
The same can be said about the protons meta to CH2 and
meta to OPhoxindole, which show up as a multiplet at
7.76 ppm. After alkylation there is also an increase of four
protons while the number of methylene protons increases
with only two.
13
C NMR spectroscopy was also used to analyse the dif-
ferent dendrons in a qualitative way. The 4-carbon atom of
3204 A. Vandendriessche et al. / European Polymer Journal 45 (2009) 31963209

Cl

Br
Cl
Cl Cl
O N Br Cl
O
O Br O
N
Cl N
Br O Cl
O O
O
Cl N N O O O
O O N
O
Br O
O O
O O
Br
CF3SO3H
20 + 6 O
60 C, 76%

N
Br O
Br
N O
Cl Cl
O
O
Cl
O O
Cl O
N
Br

Scheme 5. Synthesis of a dendrimer of rst generation with the B6 core.

Table 1
Overview of the different dendrimers with their corresponding yields.

Dendrimer B4G1 (21) B4G2 (22) B4G3 (23) B6G1 (24) B6G2 (25) B6G3 (26)
Yield (%) 85 81 80 76 72 66

Fig. 1. 1H NMR spectrum of the non-activated dendron of the 2nd generation 7.

 A. Vandendriessche et al. / European Polymer Journal 45 (2009) 31963209
Fig. 2. 1H NMR spectrum of the activated dendron of the 2nd generation 8.
the phenoxy group in the activated dendrons shows a peak
at 124.6 ppm. After reaction with 5-bromoisatin, giving
rise to the non-activated dendron of the next generation,
this peak disappears. Furthermore, by reaction of the acti-
vated dendron of the rst generation with 5-bromoisatin, a
new peak is found at 62.0 ppm due to the newly formed
triphenyl substituted quaternary carbon atom.
3.2.1.2. NMR spectra of the dendrimers. The 1H NMR spectra
of the dendrimers based on the B4 core look very similar to
the 1H NMR spectra of the corresponding dendrons. Never-
theless the presence of the core is evidenced by the appear-
ance of a new peak at 4.95 ppm as a result of the
methylene protons of this core. However, the intensity of
this peak obviously decreases with higher generation and
is hardly visible in the spectrum of the fourth generation
dendrimer. The peak at 6.69 ppm corresponds to the 7-H
isatin protons of both the dendrons and the core, which
can be seen by an increase of two in the integration value
in the spectrum of the dendrimer. The 1H NMR spectrum of
the second generation dendrimer with the tetrafunctional
core (B4G2) is given in Fig. 3.
The 1H NMR spectra of the dendrimers with a hexafunc-
tional B6 core show additional peaks characteristic for the
presence of this core. A singlet at 8.27 ppm is observed cor-
responding to the protons of C6H3(CO)3 and, a multiplet is
visible at 6.89 ppm due to the aromatic protons ortho to
OCH2CH2CH2 and the 7-H isatin protons of the core. In
addition, the aliphatic protons of the core show up as a
multiplet at both 4.04 ppm and 2.24 ppm. The relative
intensity of these core signals decreases with higher gener-
ation dendrimers. The 1H NMR spectrum of the second
generation dendrimer (B6G2) is given in Fig. 4.
3205
3.2.1.3. Mass spectrometry. The molecular structures of the
dendrons and dendrimers were also investigated with
MALDI-TOF MS measurements which serve as an excellent
analytical tool to analyze the nature of impurities. Table 2
gives an overview of theoretical masses and the masses
measured with MALDI-TOF for the different dendrons.
Fig. 5 shows the MALDI-TOF spectrum of the non-acti-
vated dendron of the second generation 7. From this spec-
trum we can conclude that this dendron is monodisperse,
which is also the case for the other dendrons. The molar
mass shown in the spectrum corresponds with the ex-
pected theoretical mass.
Table 3 gives an overview of theoretical masses and the
masses measured with MALDI-TOF for the different den-
drimers. We were not able to sufciently purify B4G4 and
B6G4.
The MALDI-TOF spectrum of the dendrimer of the rst
generation with the tetrafunctional core (B4G1) is repre-
sented in Fig. 6. The obtained molar mass corresponds
quite well with the expected theoretical mass. However,
some additional peaks can be observed in the spectrum.
The minor peak at m/z = 3339.5 corresponds to a mass
difference of one bromine atom. The minor peak at
m/z = 1945.9 corresponds to the attachment of only two
dendrons instead of four. The minor peak at m/z = 1723.3
is due to the cleavage of the core at the nitrogen-benzyl
linkage. If a bromine atom is substracted from this value,
also the peak at 1646.2 can be explained. The peaks corre-
sponding to the lack of a bromine atom are most probably
due to impure 5-bromoisatin that was used in the synthe-
sis, e.g. isatin was one of the impurities. The reason why
we nd a peak corresponding to the cleavage of the ben-
zylic position of the tetrafunctional core is most probably
the instability of the benzyl-heteroatom bond under the
3206 A. Vandendriessche et al. / European Polymer Journal 45 (2009) 31963209

Fig. 3. 1H NMR spectrum of dendrimer B4G2.

Fig. 4. 1H NMR spectrum of dendrimer B6G2.

strongly acidic conditions during the synthesis. For the
MALDI-TOF spectra of the other dendrimers with a tetra-
functional core, similar minor peaks were found.
Fig. 7 shows the MALDI-TOF spectrum of the dendrimer
of the rst generation with the hexafunctional core (B6G1).
The highest peak in the spectrum corresponds to the ex-
pected theoretical molar mass. However, some additional
peaks are also found. The peak at m/z = 5446 corresponds
to a mass difference of one bromine atom. The peak at
m/z = 5093 agrees with the loss of a 5-bromo-3,3-bis(4-
chlorophenyl)-(1,3-dihydro)indol-2-one entity (27). This
loss happens again, most probably, during the synthesis
due to the strongly acidic environment that is applied
resulting in some cleavage of the benzyl linkages, though
bearing an electron withdrawing carbonyl substituent in
the 4-position. Although the number of resulting defects
seems to be small, as can be derived from the low intensity
in the MALDI spectrum, it seems this instability will limit
 A. Vandendriessche et al. / European Polymer Journal 45 (2009) 31963209 3207

Table 2
Overview of the theoretical and measured masses of the dendrons.

Dendron Theoretical mass (g/mol) Theoretical mass + Na+ (g/mol) MALDI-TOF Na+-adduct (g/mol)
G1 Non-activated 3 431.0 454.0 /
Activated 6 719.5 742.4 /
G2 Non-activated 7 1646.9 1669.9 1669.7 (Ge)
Activated 8 1933.2 1956.2 1956.2 (Ge)
G3 Non-activated 9 4074.5 4097.5 4097.1 (Ge)
Activated 10 4360.8 4383.8 4381.5 (Leu)
G4 Non-activated 11 8929.6 8952.6 8956.2 (Ge)
Activated 12 9215.9 9238.9 9241.7 (Leu)

Fig. 5. MALDI-TOF spectrum of the non-activated dendron of the 2nd generation 7.

the scope of this dendrimer synthesis strategy to some ex-

Table 3
tent. The peak at m/z = 5017 corresponds again to a differ-
Overview of the theoretical and measured masses of the dendrimers.
ence of one bromine atom.
Dendrimer Theoretical Theoretical mass + MALDI-TOF
Cl
mass (g/mol) Na+ (g/mol) (g/mol)
B4G1 (21) 3396 3419 3420 (Leu)
B4G2 (22) 8195 8218 8197 (Leu) Cl
O
B4G3 (23) 17961 17,984 18,000 (Ge)
B6G1 (24) 5499 5522 5525 (Leu) N
H
B6G2 (25) 12,782 12,805 12,809 (Leu) Br
B6G3 (26) 27,348 27,371 27,370 (Ge) 20
27

Fig. 6. MALDI-TOF spectrum of B4G1.

3208 A. Vandendriessche et al. / European Polymer Journal 45 (2009) 31963209

5525
4000

3000

Intens. [a.u.]
5446 5556

2000

5017 5480 5812

1000 5093
5368
4935 5305 5732

5000 5200 5400 5600 5800 6000 m/z

Fig. 7. MALDI-TOF spectrum of B6G1.

3.2.1.4. Size exclusion chromatography (SEC). More infor-

Fig. 8. SEC chromatograms of dendron G2, dendrimer B4G2 and B6G2.
mation about the molecular structure and the purity of
the dendrons and dendrimers was given by SEC analyses.
The measurements were carried out in THF using polysty-
rene standards. The chromatograms of the activated den-
drons of the second generation (G2 = 8), B4G2 and B6G2
are given in Fig. 8. The SEC data of the dendrons and den-
drimers are summarized in Tables 4 and 5.
The apparent molar mass dispersity for the different
dendrons and dendrimers listed is in all cases narrow, only
slightly deviating from the theoretical value of 1 for pure
dendrimers, presumably due to diffusion broadening in
the GPC columns. B4G4 and B6G4 are not included in Table
5. The multimodal chromatograms suggest that in these

Table 4
SEC results of the dendrons.

Dendron Theor. massa (g/mol) Mn (g/mol) Mw (g/mol) D Mpb (g/mol) Relative deviationc
G1 Activated 719    
G2 Non-activated 1646 1.4  103 1.5  103 1.07 1600 0.0279
Activated 1933 1.6  103 1.7  103 1.08 1874 0.0305
G3 Non-activated 4074 3.7  103 3.9  103 1.06 4035 0.00957
Activated 4361 3.9  103 4.1  103 1.05 4336 0.00573
G4 Non-activated 8930 7.6  103 8.1  103 1.07 8166 0.0856
Activated 9216 7.6  103 8.1  103 1.07 8037 0.128
a
Theoretical molar mass.
b
Peak molar mass.
c
Relative deviation = (Mp,meas.  Mp,theor)/Mp,theor.

Table 5
SEC results of the dendrimers.

Dendrimer Theor. massa (g/mol) Mn (g/mol) Mw (g/mol) D Mpb (g/mol) Relative deviationc
B4G1 3396 2.9  103 3.1  103 1.06 3313 0.0244
B4G2 8195 6.7  103 7.1  103 1.07 7194 0.122
B4G3 17,961 10  103 12  103 1.16 12,236 0.319
B6G1 5499 4.6  103 4.7  103 1.04 4909 0.107
B6G2 12,782 9.4  103 10  103 1.07 9662 0.244
B6G3 27,348 16  103 18  103 1.10 17,032 0.377
a
Theoretical molar mass.
b
Peak molar mass.
c
Relative deviation = (Mp,meas.  Mp,theor)/Mp,theor.
 A. Vandendriessche et al. / European Polymer Journal 45 (2009) 31963209
cases, the functionalization of the core is likely to be
incomplete. In many SEC traces (as can be seen for B4G2
and B6G2 in Fig. 8), a small shoulder can be observed at
the high molar mass side, probably due to a small amount
of cross linking products which could not be removed.
4. Conclusions
We succeeded in synthesizing a new class of poly(aryl-
ene oxindole) dendrimers in good yield applying the
superelectrophilic properties of isatin. We could synthe-
size up to 4th generation dendrons and 3th generation
dendrimers with a B4 and B6 core. NMR, MALDI-TOF MS
and SEC analyses conrmed their regular molecular archi-
tecture. SEC analysis with linear polystyrene standards re-
vealed the narrow molar mass dispersity of the dendrons
and dendrimers. The utilization of the MALDI-TOF MS
technique was of particular importance to conrm the
structures. However, these spectra showed some signals
corresponding to the cleavage at the benzylic positions of
the B4 core as well as the cleavage of the benzylic positions
of the AB2 monomeric units. This suggests that the dendri-
mers are not completely stable in the triuoromethanesul-
fonic acid used during the synthesis, which is likely to limit
the applicability of the described strategy. In future work,
we will attempt to address this issue.
Acknowledgements
We gratefully acknowledge nancial support by the
K.U. Leuven, the ministerie voor wetenschapsbeleid, IWT-
Vlaanderen and FWO-Vlaanderen. A.V. and S.D. thank the
Institute for the Promotion of Innovation through Science
3209
and Technology in Flanders (IWT-Vlaanderen), B.D. thanks
the FWO-Vlaanderen for a Ph.D. scholarship, J.T. thanks the
K.U. Leuven, J.H. thanks the FWO-Vlaanderen for postdoc-
toral fellowship. W.D. and F.D.P. thank the Belgian Program
on Interuniversity Attraction Poles initiated by the Belgian
State, Prime Ministers ofce (Program P6/27) for nancial
support.
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