Synthesis of periphery-functionalized dendritic polyethers

Article abstract of DOI:10.1016/j.tet.2003.12.003

New dendritic polyethers with bromo-, hydroxy- and vinyl-end groups have been synthesized by a convergent strategy. Planar, 1,3,5- trischlorocarbonylbenzene and 1,3,5-trihydroxybenzene, and tetrahedral, tetrakis(p-hydroxyphenyl)methane, cores have been used.

Full text of DOI:10.1016/j.tet.2003.12.003

Tetrahedron 60 (2004) 1563–1569
Synthesis of periphery-functionalized dendritic polyethers
*
Enrique Dıez-Barra, Raquel Gonzalez, Prado Sanchez-Verdu and Juan Tolosa
´
´
´
´
´ ´ ´
Departamento de Quımica Organica, Facultad de Ciencias Quımicas, Campus Universitario,
Universidad de Castilla-La Mancha, 13071 Ciudad Real, Spain
Received 2 June 2003; revised 4 September 2003; accepted 2 December 2003
Abstract—New dendritic polyethers with bromo-, hydroxy- and vinyl-end groups have been synthesized by a convergent strategy. Planar,
1,3,5-trischlorocarbonylbenzene and 1,3,5-trihydroxybenzene, and tetrahedral, tetrakis(p-hydroxyphenyl)methane, cores have been used.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
resorcinol to built dendrimers derived from core 2.11 In
2002, the transformation of 2 in a extended core by reaction
with 1,5-dibromopentane was described.12 In all these
papers, the dendritic growth was effected by a Williamson
reaction. Also in 1996 was reported the use of 2 as core and
a focal-pointed carboxyl dendron.13 In 2002, dendrons
having chlorocarbonyl as focal point have been connected
to 2.14 The tetrahedral core 3 was used for the first time in
this work.
The synthesis and applications of new dendrimeric
structures have been the focus of several research teams.
Synthetic methodologies, involving convergent1 and
divergent2 routes have been reviewed.3 Other strategies
involving ‘hypermonomers’,4 exponential5 and orthogonal6
growth, and ‘activated’ monomers7 have also been reported.
Polyether backbones have been widely used for preparing
8
dendritic architectures by Frechet’s convergent strategies.
´
3,5-Dihydroxybenzyl alcohol has been used as keystone for
preparing a large number of dendrons and dendrimers via
the iterative use of the Williamson reaction.
2. Results
Figure 1 shows the hydroxy-(A) and bromo-(B) dendrons
used in this work. A-type dendrons were prepared by
reacting the appropriate benzyl halides with 3,5-dihydroxy-
benzyl alcohol. B-type dendrons were prepared by reacting
A-type dendrons with Br4C/Ph3P. In the case of 7B, these
reaction conditions provoked the deprotection of phenolic
hydroxy groups. Dendron 7B was conveniently prepared by
mesylation of 7A followed by reaction with sodium
bromide.
Modification of functional groups on the periphery of a
dendritic structure offers a convenient route to new
dendrimers with a structure of the external generation
different from that of the first generations. This approach
has been mainly used for preparing dendrimers with
catalytically active centers on the periphery.9
This work aims at the synthesis of new periphery-
functionalized dendritic polyethers having planar and
tetrahedral cores.
Benzyl halides were reacted with 3,5-dihydroxybenzyl
alcohol in acetone/K2CO3 to give the corresponding
A-dendrons. Commercial benzyl bromide, p-bromobenzyl
bromide and p-vinylbenzyl chloride were used without
further purification. Although the synthesis of 7A by
reduction of methyl 3,5-bis(tert-butyldimethylsilyloxy)-
benzoate with HLA had been reported,15 we prepared 7A
by a two-step sequence involving the protection of the
three hydroxy groups of 3,5-dihydroxybenzyl alcohol with
tert-butyldimethylsilyl chloride followed by selective
deprotection of the benzylic hydroxy group with Oxonew.
This procedure followed a recent communication16 des-
cribing a similar cleavage on less functionalized tert-
butyldimethylsilyl ethers. Dendron 8A was prepared as
described in Scheme 1. Hydroquinone was sequentially
The versatile hydroxy-, bromo- and vinyl groups have been
chosen as peripheral groups and 1,3,5-trischlorocarbonyl
benzene, 1, 1,3,5-trihydroxybenzene, 2, and tetrakis-
(p-hydroxyphenyl) methane, 3 have been selected as
cores. Core 1 has been widely used in dendrimer synthesis.
Core 2 has been used only in few occasions. Chow10
reported in 1996 the reaction of 2 with 1,3-dibromopropane
to prepare polyether dendrons with a hydroxy group as focal
point. In 1997, he also reported the use of 5-benzyloxy-
Keywords: Dendrimers; Polyether; Cross-linkers.
*
Corresponding author. Tel.: þ34-926295337; fax: þ34-926295318;
e-mail address: enrique.diez@uclm.es
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.12.003

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1564
Figure 1. Hydroxy-(A) and bromo-(B) dendrons used in this work.
O,O-disubstituted by reactions with p-vinylbenzyl chloride
and 2-chloroethyloxyethanol. Reaction with Br4C/Ph3P
yielded the corresponding bromide, which was reacted
with 3,5-dihydroxybenzyl alcohol giving 8A.
Chart 1. Periphery-functionalized dendrimers with 1,3,5-tris(oxycarbonyl)
benzene 1 as core.
Reactions of type-A dendrons with core 1 yielded
dendrimers with ester connectivity. Esterification was
performed in the presence of 4-dimethylaminopyridine
following a standard procedure.17 Dendrimer 10 was
deprotected by hydrogenation yielding a new hypercore
bearing six hydroxy groups 11. Dendrimer 12 having
peripheral p-bromophenyl groups could be useful to prepare
differently substituted dendrimers.18 Dendrimers 13 and 14
having peripheral vinyl groups are useful cross-linker in
polymerization.19 Attempts to deprotect dendrimer 15 failed
probably as a result of competitive oxidation processes.
However, this dendrimer could be considered as a latent
form of the hydroxylic hypercore 11. Deprotection with KF
followed by reaction with benzyl bromides in a one-pot
procedures has been reported for related compounds.20
Connections to core 2 have been usually achieved by
Williamson’s reactions. We have also tested the Mitsunobu
reaction. Results were satisfactory for small dendrons (5A
and 7A) but the reaction failed with a larger dendron 8A or a
second generation dendron 9A. Dendrimers 16 and 17 were
also prepared by Mitsunobu reactions (Chart 1).
It is known that peripheral p-bromo substituted dendrimers
can be used for preparing new dendrimers.18 Thus,
dendrimer 16 was reacted with n-butyllithium to give the
Chart 2. Pheriphery-functionalized dendrimers with phoroglucinol
(1,3,5-trihydroxybenzene) 2 as core.
Scheme 1. Preparation of dendron 8A.

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1565
Table 1. Chemical shifts (d, ppm) for benzylic methylenes
and 8B were reacted with core 3 following the standard
procedure (K2CO3/acetone). Dendrimers 18 and 19 are also
useful molecules for preparing polymeric support.
Compound
6A
7A
8A
9A
6B
8B
a
GF-CH2
End-CH2
4.62
5.02
4.56
–
4.60
4.99
4.61
4.96
4.41
5.02
4.38
4.99
b
The characterization of all new compounds have been
1
performed by HRMS (except dendrimers) and H and 13C
Compound
a
10
5.34
5.01
11
5.30
–
12
5.35
4.97
13
5.33
5.00
14
5.28
4.97
15
5.28
–
NMR and their chemical shifts are indicated in Section 3.
The signals of the different benzylic methylene groups
(Table 1) are significant and have been used for verify both
the completion of the reactions and, the purity (.95%) of
the dendrimers (Chart 3).
GF-CH2
End-CH2
b
Compound
a
16
4.93
4.97
17
4.88
—
18
4.95
5.02
19
4.91
4.96
GF-CH2
End-CH2
b
a
Methylene close to the focal point or the core.
Methylene close to the periphery.
In conclusion, new hydroxy-, bromo- and vinyl end-capped
dendritic polyethers have been prepared. Both ester and
ether connectivities have been employed. Ether connectivity
of small dendrons has been successfully performed
under Mitsunobu reaction conditions. The tetrahedral core
tetrakis(p-hydroxyphenyl) methane have been used for the
first time.
b
dendritic hexa-anion as shown by a reaction with chloro-
trimethylsilane. 1H NMR spectra showed the complete
substitution on the peripheral six phenyl rings. Dendrimer
17 can be considered as a latent hydroxylic core (Chart 2).
Core 3 was prepared from the corresponding tetraamino
derivative21 by reaction with NaNO2/H2SO4 followed by
hydrolysis of the tetradiazonium salt. Attempts to apply the
Mitsunobu conditions to dendron 6A failed. Dendrons 6B
3. Experimental
3.1. General considerations
All starting materials were purchased from Aldrich
chemical Co. and Acros and were used without further
purification. The following chemicals were prepared
according to literature procedures: 3,5-bis(benzyloxy)-
benzyl alcohol (4A),1 3,5-bis(benzyloxy)benzyl bromide
(4B),1 3,5-bis(p-bromophenylmethyloxy)benzyl alcohol
(5A),22 3,5-bis(p-bromophenylmethyloxy)benzyl bromide
(5B)22 and 3,5-bis[3,5-bis(p-bromophenylmethyloxy)phenyl-
methyloxy] benzyl alcohol (9A).22 All solvents used for
extractions or reactions were dried according to standard
procedures and kept over molecular sieves. Flash chroma-
tography was run on 230–400 mesh silica-gel (Merck).
NMR spectra were recorded in CDCl3 using a VARIAN
UNITY 300 spectrometer operating at 299.980 MHz for
proton and 75.423 MHz for carbon-13 at a temperature of
293 K. Mass spectrometry was performed at the SIDI
´
(Universidad Autonoma of Madrid).
3.1.1. Tetrakis(p-hydroxyphenyl)methane (3). Tetrakis-
(p-aminophenyl)methane21 (760 mg, 2 mmol) was placed in
20 mL of water and sulfuric acid (98%) was added dropwise
until complete dissolution of the reactive. The reaction was
then cooled to 0 8C and a solution of sodium nitrite (610 mg,
8.8 mmol) in 10 mL of water was added dropwise. The
reaction mixture was stirred for 15 min. A solution of
concentrated sulfuric acid (0.5 mL) in water (10 mL) was
added and the reaction heated at 50 8C for 2 h. The solution
was extracted with ethyl acetate (20 mL£3) and the
combined organic layers were dried over MgSO4. The
crude product was purified by column chromatography
(ethyl acetate). The desired compound was obtained as a
brown solid after crystallization from methanol/chloroform.
Mp: .270 8C. Yield 32%. 1H NMR, d (d6-DMSO): 9.26 (s,
4H); 6.84 and 6.80 (d, 8H, A2 of A2B2 system, J¼8 Hz);
6.60 and 6.40 (d, 8H, B2 of A2B2 system, J¼8 Hz). 13C
NMR, d (d6-DMSO): 154.6, 137.8, 131.2, 114.0 and 61.4.
MS (EI), m/z: 384 (Mþ). HRMS, calcd for C25H20O4
384.1362, found 384.1382.
Chart 3. Peryphery-functionalized dendrimers with tetrakis(p-hydroxy-
phenyl)methane 3 as core.

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1566
3.2. Preparation of dendrons
(M)þHRMS, calcd for C45H48O9 732.3298, found
732.3329.
3.2.1. 3,5-Bis(p-vinylphenylmethyloxy)benzyl alcohol
(6A). A mixture of 3,5-dihydroxybenzyl alcohol (1.4 g,
10 mmol), 4-vinylbenzyl chloride (3.2 g, 21 mmol), potas-
sium carbonate (3.0 g, 22 mmol) and Aliquat 336 (5 mol%)
in 35 mL of acetone was placed in a 100 mL round-bottom
flask fitted with a condenser reflux. The reaction was heated
for 12 h at 80 8C. Inorganic salts and Aliquat 336 were
carried out by filtration over Florisilw, the solvent was
evaporated and the crude product was crystallized in ethyl
acetate/hexane as a white solid. Mp: 63–5 8C. Yield 90%.
1H NMR, d: 7.44 and 7.40 (d, 4H, A2 of A2B2 system,
J¼8 Hz); 7.38 and 7.34 (d, 4H, B2 of A2B2 system,
J¼8 Hz); 6.72 (dd, 2H, Jtrans¼18 Hz, Jcis¼11 Hz); 6.61
(d, 2H, J¼2 Hz); 6.53 (t, 1H, J¼2 Hz); 5.76 (dd, 2H,
Jgem¼1 Hz, Jtrans¼18 Hz); 5.26 (dd, 2H, Jgem¼1 Hz, Jcis¼
11 Hz); 5.02 (s, 4H); 4.62 (s, 2H). 13C NMR, d: 160.6,
143.9, 137.9, 136.9, 128.2, 126.9, 114.6, 112.8, 106.3,
101.9, 70.4 and 65.8. MS (EI), m/z: 372 (M)þHRMS, calcd
for C25H24O3 372.1725, found 372.1712.
3.2.4. 4-(p-Vinylphenylmethyloxy)phenol. A mixture of
1,4-hydroquinone (8.8 g, 80 mmol), 4-vinylbenzyl chloride
(3.0 g, 20 mmol), potassium carbonate (2.8 g, 20 mmol) and
Aliquat 336 (2 mmol) in acetone (75 mL) was placed in a
250 mL round-bottomed flask fitted with a condenser reflux.
The reaction mixture was heated for 24 h at 80 8C. The
inorganic salts were filtered off and the solvent was
evaporated. Chloroform (75 mL) was added to precipitate
the excess of 1,4-hydroquinone, which was removed
together with the Aliquat 336 by filtration over Florisil.
The solvent was evaporated and the crude product was
purified by column chromatography (hexane/ethyl acetate,
1
9:1). Mp: 143–4 8C (ethyl acetate/hexane). Yield 62%. H
NMR, d: 7.44 and 7.41 (d, 2H, A2 of A2B2 system, J¼8 Hz);
7.39 and 7.36 (d, 2H, B2 of A2B2 system, J¼8 Hz); 6.87–
6.67 (m, 5H); 5.75 (dd, 1H, Jgem¼1 Hz, Jtrans¼18 Hz); 5.25
(dd, 2H, Jgem¼1 Hz, Jcis¼11 Hz); 4.99 (s, 2H). 13C NMR, d:
153.0, 149.7, 137.3, 136.8, 136.5, 127.7, 126.4, 116.1, 114.0
and 70.5. MS (EI), m/z: 226 (M)þHRMS, calcd for
C15H14O2 226.0994, found 226.1009.
3.2.2. 3,5-Bis(tert-butyldimethylsilyloxy)benzyl alcohol
(7A).15 In a 250 mL round-bottomed flask, O,O,O-tris-
(tert-butyldimethylsilyloxy)benzyl
alcohol
(490 mg,
3.2.5. 1-(Hydroxyethyleneoxyethyleneoxy)-4-(p-vinyl-
phenyloxymethyloxy)benzene. A mixture of 4-(p-vinyl-
phenylmethyloxy)phenol (2.3 g, 10 mmol), KOH (840 mg,
15 mmol), 2-(2-chloroethoxy)ethanol (1.5 g, 12 mmol) and
TBAB (9 mol%) was heated without solvent for 32 h at
80 8C. Acetone was added and the inorganic salts were
filtered off. The crude product was purified by column
chromatography (hexane/ethyl acetate, 3:1); when the
undesired products were carried out, ethyl acetate was
used as eluent. The product was obtained as a white solid.
Mp: 100–1 8C. Yield 60%. 1H NMR, d: 7.44 and 7.40
(d, 4H, A2 of A2B2 system, J¼8 Hz); 7.39 and 7.35 (d, 4H,
B2 of A2B2 system, J¼8 Hz); 6.91–6.81 (m, 4H); 6.72 (dd,
2H, Jtrans¼18 Hz, Jcis¼11 Hz); 5.75 (dd, 2H, Jgem¼1 Hz,
Jtrans¼18 Hz); 5.25 (dd, 2H, Jgem¼1 Hz, Jcis¼11 Hz); 5.00
(s, 2H); 4.09 (t, 2H, J¼4 Hz); 3.83 (t, 2H, J¼4 Hz); 3.74
(t, 2H, J¼4 Hz); 3.68 (t, 2H, J¼4 Hz). 13C NMR, d: 153.2,
153.0, 137.3, 136.8, 136.5, 127.7, 126.4, 115.9, 115.7,
114.0, 72.5, 70.4, 69.8, 68.1 and 61.8. MS (EI), m/z: 314
(M)þHRMS, calcd for C19H22O4 314.1518, found 314.1541.
1 mmol) was dissolved in ethanol (80 mL) and a solution
of Oxonew (614 mg, 1 mmol) in the minimum amount of
water was added dropwise. The reaction was stirred at room
temperature. The reaction was monitored by GC to fix the
reaction time (4 h) avoiding higher level of deprotection.
Inorganic salts were filtered off and the ethanol was
evaporated. Water (25 mL) was added and the reaction
was extracted with ethyl acetate (25 mL£3). The organic
layer was dried over MgSO4, and the solvent was
evaporated after filtration. The crude product was purified
by column chromatography (hexane/ethyl acetate 5:1). Mp:
1
45–6 8C. Yield 52%. H NMR, d: 6.46 (d, 2H, J¼2 Hz);
6.26 (t, 1H, J¼2 Hz); 4.56 (s, 2H); 0.97 (s, 9H); 0.19 (s, 6H).
13C NMR, d: 156.5, 111.7, 111.1, 94.4, 65.2, 25.8, 18.3 and
24.2. MS (EI), m/z: 368 (Mþ).
3.2.3. 3,5-Bis(p-vinylphenylmethyloxy-p-phenyloxyethyl-
eneoxyethylenoxy)benzyl alcohol (8A). A mixture of
1,4-(bromoethyleneoxyethyleneoxy), (p-vinylphenyloxy-
methyloxy)benzene (1.0 g, 2.65 mmol), KOH (154 mg,
2.70 mmol), 3,5-dihydroxybenzyl alcohol (180 mg,
1.07 mmol) and tetrabutyl ammonium bromide (TBAB)
(9 mol%) was heated without solvent for 24 h at 80 8C.
Ethyl acetate (20 mL) was added, the inorganic salts were
filtered off and the solvent was evaporated. The crude
product was purified by column chromatography (hexane/
ethyl acetate 1:1). The desired compound was obtained as a
white solid after crystallization from ethanol. Mp: 105–
3.2.6. 1,4-(Bromoethyleneoxyethyleneoxy)(p-vinylphenyl-
oxymethyloxy)benzene. In a previously flamed Schlenk
tube was placed carbon tetrabromide (5.1 g, 15 mmol),
1,4-(hydroxyethyleneoxyethyleneoxy),(p-vinylphenyloxy-
methyloxy)benzene (1.3 g, 4 mmol) and triphenylphosphine
(4.0 g, 15 mmol); dry THF was added (20 mL) and the
mixture was stirred at room temperature under Ar
atmosphere for 4 h. Triphenylphosphonium oxide formed
was filtered off and the solvent was evaporated. The crude
product was purified by column chromatography (hexane/
ethyl acetate, 8:1). For further purification the product was
1
7 8C. Yield 68%. H NMR, d: 7.44 and 7.40 (d, 4H, A2 of
A2B2 system, J¼8 Hz); 7.39 and 7.35 (d, 4H, B2 of A2B2
system, J¼8 Hz); 6.91–6.81 (m, 8H); 6.72 (dd, 2H,
Jtrans¼18 Hz, Jcis¼11 Hz); 6.53 (d, 2H, J¼2 Hz); 6.43
(t, 1H, J¼2 Hz); 5.75 (dd, 2H, Jgem¼1 Hz, Jtrans¼18 Hz);
5.25 (dd, 2H, Jgem¼1 Hz, Jcis¼11 Hz); 4.99 (s, 4H);
4.60 (s, 2H); 4.07–4.15 (m, 8H); 3.92–3.86 (m, 8H). 13C
NMR, d: 160.1, 153.1, 143.3, 137.3, 136.8, 136.5,
127.7, 126.4, 115.8, 115.7, 114.0, 105.6, 100.9, 99.4, 70.4,
70.0, 69.9, 68.2, 67.6 and 65.3. MS (EI), m/z: 732
1
crystallized from ethanol. Mp: 72–4 8C. Yield 87%. H
NMR, d: 7.44 and 7.40 (d, 4H, A2 of A2B2 system, J¼8 Hz);
7.39 and 7.35 (d, 4H, B2 of A2B2 system, J¼8 Hz);
6.91–6.81 (m, 4H); 6.72 (dd, 2H, Jtrans¼18 Hz, Jcis¼11
Hz); 5.75 (dd, 2H, Jgem¼1 Hz, Jtrans¼18 Hz); 5.25 (dd, 2H,
Jgem¼1 Hz, Jcis¼11 Hz); 5.00 (s, 2H); 4.09 (t, 2H, J¼4 Hz);
3.91–2.82 (m, 4H); 3.49 (t, 2H, J¼6 Hz). 13C NMR, d:

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1567
153.2, 153.0, 137.3, 136.8, 136.5, 127.7, 126.4, 115.9,
115.7, 114.0, 71.4, 70.4, 69.8, 68.2 and 30.2. MS (EI), m/z:
376 (M)þ, 378 (Mþ2)þHRMS, calcd for C19H21BrO2
376.0674, found 376.0651and 378.0670.
(dd, 2H, Jgem¼1 Hz, Jcis¼11 Hz); 4.99 (s, 4H); 4.38 (s, 2H);
4.15–4.07 (m, 8H); 3.92–3.86 (m, 8H). 13C NMR, d: 160.1,
153.3, 139.9, 137.5, 137.1, 136.7, 127.9, 126.7, 116.2, 116.0,
114.3, 108.4, 105.9, 102.2, 70.9, 70.5, 70.2, 68.6, 68.1 and
34.0. HRMS (L-SIMS), m/z calcd for C45H47BrO8 794.2454,
found 794.2441 (MþH)þand 796.2456 (MþHþ2)þ.
3.2.7. 3,5-Bis(p-vinylphenylmethyloxy)benzyl bromide
(6B). To a solution of 6A (1.0 g, 2.7 mmol) in the minimum
amount of dry THF (10 mL), carbon tetrabromide (1.2 g,
3.38 mmol) and triphenylphosphine (880 mg, 3.38 mmol)
were added. The mixture was stirred at room temperature
for 20 min. Water (20 mL) was added and the aqueous layer
was extracted with methylene chloride (20 mL£3). The
combined organic extracts were dried over MgSO4 and
evaporated to dryness. The crude product was purified by
column chromatography (hexane/ethyl acetate, 3:1) to give
the pure product as a white solid. Mp: 78–9 8C. Yield 65%.
1H NMR, d: 7.44 and 7.40 (d, 4H, A2 of A2B2 system,
J¼8 Hz); 7.38 and 7.34 (d, 4H, B2 of A2B2 system,
J¼8 Hz); 6.72 (dd, 2H, Jtrans¼18 Hz, Jcis¼11 Hz); 6.61
(d, 2H, J¼2 Hz); 6.53 (t, 1H, J¼2 Hz); 5.76 (dd, 2H,
Jgem¼1 Hz, Jtrans¼18 Hz); 5.26 (dd, 2H, Jgem¼1 Hz, Jcis¼
11 Hz); 5.02 (s, 4H); 4.41 (s, 2H). 13C NMR, d: 159.8,
139.6, 137.3, 136.3, 136.0, 127.6, 126.3, 114.1, 108.2,
102.2, 70.0 and 33.6. MS (EI), m/z: 434 (M)þ, 436
(Mþ2)þHRMS, calcd for C25H23BrO2 434.0881, found
434.0894 and 436.0861 (Mþ2).
3.3. Preparation of dendrimers
General procedure for dendrimers with ester connectivity.
In a previously flamed Schlenk tube, equimolar amounts of
the corresponding dendron and 4-dimethylaminopyridine
under Ar atmosphere were dissolved in dry dichloromethane
(3 mL/mmol). 1,3,-benzenetricarboxylic acid chloride
(33 mol%) was added dropwise. The reaction was stirred
at room temperature for 4 h. The 4-dimethylaminipyridium
chloride formed was filtered off and the solvent was
evaporated. Pure products were purified as indicated below.
3.3.1. 3,5-Bis(phenylmethyloxy)phenylmethyl 1,3,5-
benzenetricarboxylate (10). The pure product was
obtained as a with solid after crystallization from ethyl
acetate/hexane. Mp: 112–4 8C. Yield 1.83 g, 94%. 1H
NMR, d: 8.90 (s, 3H); 7.41–7.28 (m, 30H); 6.68 (t, 3H,
J¼2 Hz); 6.58 (t, 3H, J¼2 Hz); 5.34 (s, 6H); 5.01 (s, 12H).
13C NMR, d: 164.7, 160.1, 137.7, 136.6, 134.9, 131.2,
128.6, 128.0, 127.5, 107.3, 102.0, 70.1 and 67.2. MS
(MALDI-TOF), m/z: 1139.3 (MþNa)þ.
3.2.8. 3,5-Bis(tert-butyldimethylsilyloxy)benzyl bromide
(7B). In a previously flamed Schlenk tube a solution of 7A
(1.104 g, 3 mmol) in dry dichloromethane (15 mL) and dry
triethylamine (455 mg, 4.5 mmol) was placed, the mixture
was cooled to 0 8C under argon atmosphere. Methane-
sulfonyl chloride (412 mg, 3.6 mmol) was added dropwise
and the reaction was stirred for 30 min. Then, a solution of
LiBr (2.60 g, 30 mmol) in dry acetone (17 mL) was added
and the reaction was stirred at RT for 3 h. Inorganic salts
were filtered off over Celitew 545 and the solvent was
evaporated. 15 mL of diethyl ether was added to precipitate
the excess of LiBr which was filtered off. The solvent was
evaporated and the pure product was isolated as a white
3.3.2. 3,5-Bis(p-bromophenylmethyloxy)phenylmethyl
1,3,5-benzenetricarboxylate (12). The pure product was
obtained as a white solid after crystallization from ethyl
1
acetate/hexane. Mp: 149–51 8C. Yield 842 mg, 95%. H
NMR, d: 8.90 (s, 3H); 7.47 and 7.45 (d, 12H, A2 of A2B2
system, J¼8 Hz); 7.26 and 7.24 (d, 12H, B2 of A2B2 system,
J¼8 Hz); 6.65 (d, 6H, J¼2 Hz); 6.51 (t, 3H, J¼2 Hz);
5.35 (s, 6H); 4.97 (s, 12H). 13C NMR, d: 164.4, 159.6,
137.7, 135.5, 134.7, 131.5, 131.0, 128.9, 121.8, 107.3,
102.0, 69.3 and 67.1. MS (MALDI-TOF)), m/z: 1612.9
(MþNaþ6)þ(100), 1614.9 (MþHþ8)þ(86).
1
solid. Mp: 40–1 8C. Yield 73%. H NMR, d: 6.44 (d, 2H,
J¼2 Hz); 6.21 (t, 1H, J¼2 Hz); 4.30 (s, 2H); 0.93 (s, 18H);
0.15 (s, 12H). 13C NMR, d: 156.3, 111.5, 111.0, 94.6, 34.0,
25.8, 18.3, 24.2. MS (EI), m/z: 430 (M)þ, 432 (Mþ2)þ.
HRMS, calcd for C13H23Si2O2 346.0420, found 346.0448
and 348.0457 (Mþ2).
3.3.3. 3,5-Bis(p-vinylphenylmethyloxy)phenylmethyl
1,3,5-benzenetricarboxylate (13). The pure product was
obtained as a white solid after crystallization from ethyl
acetate/hexane. Mp: 113–5 8C. Yield 1.36 g, 90%. 1H
NMR, d: 8.90 (s, 3H); 7.39 and 7.36 (d, 12H, A2 of A2B2
system, J¼8 Hz); 7.35 and 7.32 (d, 12H, B2 of A2B2 system,
J¼8 Hz); 6.73–6.63 (m, 12H); 6.56 (t, 3H, J¼2 Hz);
5.72 (dd, 6H, Jgem¼1 Hz, Jtrans¼18 Hz); 5.33 (s, 6H);
5.23 (dd, 6H, Jgem¼1 Hz, Jcis¼11 Hz); 5.00 (s, 12H). 13C
NMR, d: 167.6, 160.1, 137.7, 136.4, 136.1, 134.9, 131.2,
127.7, 126.4, 114.1, 107.3, 102.1, 69.9 and 67.2. MS
(MALDI-TOF), m/z: 1295.5 (MþNa)þ.
3.2.9. 3,5-Bis(p-vinylphenylmethyloxy-p-phenyloxyethyl-
eneoxyethyleneoxy)benzyl bromide (8B). To a solution of
8A (2.9 g, 4 mmol) in the minimum amount of dry THF,
carbon tetrabromide (1.7 g, 5 mmol) and triphenylphos-
phine (1.3 g, 5 mmol) were added. The mixture was stirred
at room temperature for 20 min. Water (20 mL) was added
and the aqueous layer was extracted with methylene
chloride (20 mL£3). The combined organic extracts were
dried over MgSO4 and evaporated to dryness. The crude
product was purified by column chromatography (chloro-
form) to give the pure product as a white solid. Mp:
66–8 8C. Yield 63%. 1H NMR, d: 7.44 and 7.40 (d, 4H, A2
of A2B2 system, J¼8 Hz); 7.38 and 7.34 (d, 4H, B2 of A2B2
system, J¼8 Hz); 6.91–6.81 (m, 8H); 6.72 (dd, 2H,
Jtrans¼18 Hz, Jcis¼11 Hz); 6.53 (d, 2H, J¼2 Hz); 6.43 (t,
1H, J¼2 Hz); 5.75 (dd, 2H, Jgem¼1 Hz, Jtrans¼18 Hz); 5.25
3.3.4. 3,5-Bis(tert-butyldimethylsilyloxy)benzyl 1,3,5-
benzene tricarboxylate (15). The crude of the reaction
was dissolved in CH2Cl2 (20 mL) and washed with water
(15 mL x 3). The organic layer was dried over MgSO4 and
filtered over silica to remove the excess of DMAP. After
evaporation of the solvent the pure product was isolated
as a white solid. Mp: 91–3 8C. Yield 73%. 1H NMR, d: 8.89
(s, 3H) 6.53 (d, 6H, J¼2 Hz); 6.29 (t, 3H, J¼2 Hz); 5.28
(s, 6H); 0.96 (s, 54H); 0.18 (s, 36H). 13C NMR, d: 164.7,

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E. Dıez-Barra et al. / Tetrahedron 60 (2004) 1563–1569
1568
156.7, 137.4, 134.8, 131.4, 113.3, 112.1, 67.2, 26.0, 18.5
and 24.0. MS (MALDI-TOF), m/z: 1283.3 (MþNa)þ.
16H, B2 of A2B2 system, J¼8 Hz), 7.05 (d, 8H, A2 of A2B2
system (core), J¼8 Hz); 6.86–6.63 (m, 48H); 6.58 (d, 8H,
J¼2 Hz); 6.44 (t, 4H, J¼2 Hz); 5.75 (dd, 8H, Jgem¼1 Hz,
Jtrans¼18 Hz); 5.25 (dd, 8H, Jgem¼1 Hz, Jcis¼11 Hz); 4.96
(s, 16H); 4.91 (s, 8H); 4.08 (m, 32H); 3.87 (m, 32H). 13C
NMR, d: 159.9, 156.5, 153.0, 139.8, 139.4, 137.1, 136.7,
136.3, 131.9, 131.7, 127.5, 126.2, 115.8, 115.6, 113.9,
113.5, 106.2, 101.2, 99.5, 70.5, 70.1, 69.9, 68.2, 67.6 and
64.8. MS (MALDI-TOF), m/z: 3264.1 (MþNa)þ.
3.3.5. 3,5-Bis(p-vinylphenylmethyloxy-p-phenyloxyethyl-
ene-oxyethyleneoxy)phenylmethyl 1,3,5-benzenetricarb-
oxylate (14). The pure product was obtained after crystal-
lization from dichloromethane/ethanol. Mp: 52–5 8C. Yield
1
413 mg, 63%. H NMR, d: 8.87 (s, 3H); 7.43 and 7.39 (d,
12H, A2 of A2B2 system, J¼8 Hz); 7.37 and 7.33 (d, 12H,
B2 of A2B2 system, J¼8 Hz); 6.73 (dd, 6H, Jcis¼11 Hz,
Jtrans¼18 Hz); 6.59 (d, 6H, J¼2 Hz); 6.48 (t, 3H, J¼2H);
5.74 (dd, 6H, Jgem¼1 Hz, Jtrans¼18 Hz); 5.28 (s, 6H); 5.25
(dd, 6H, Jgem¼1 Hz, Jcis¼11 Hz); 4.97 (s, 12H); 4.09 (m,
24H); 3.87 (m, 24H). 13C NMR, d: 164.6, 160.1, 153.1,
137.6, 137.2, 136.8, 136.4, 134.9, 131.2, 127.6, 126.3,
115.8, 115.6, 114.0, 107.1, 101.6, 99.4, 70.4, 70.0, 69.8,
68.1, 67.6 and 67.2. MS (MALDI-TOF), m/z: 2375.7
(MþNa)þ.
3.4. Dendrimers with ether connectivity (Mitsunobu
conditions)
3.4.1. 1,3,5-Tris[3,5-bis(p-bromophenylmethyloxy)phenyl-
methyloxy]benzene (16). In a previously flamed Schlenk a
mixture of phloroglucinol (126 mg, 1 mmol), 5A (2.4 g,
5 mmol) and triphenylphosphine (1.1 g, 4 mmol) was
dissolved in dry THF (15 mL) under argon atmosphere. A
solution of DEAD (695 mg, 4 mmol) in dry THF (5 mL)
was added dropwise and the reaction was stirred at room
temperature overnight. The solvent was evaporated and
diethyl ether was added to precipitate the desired compound
with a little amount of triphenylphosphine, the crude
product was purified by crystallization from ethyl acetate/
3.3.6. (3,5-Dihydroxyphenyl)methyl 1,3,5-benzene-
tricarboxylate (11). 3,5-Bis(phenylmethyloxy)phenyl-
methyl 1,3,5-benzenetricarboxylate (1.1 g, 1 mmol) and
palladium over carbon (6 mol%) was suspended in
dimethoxyethane (20 mL) and the reaction mixture was
stirred at room temperature under H2 atmosphere until the
expected volume of H2 was consumed. Palladium over
carbon was filtered off over Celite 545w and the solvent was
evaporated. The pure product was obtained as a pale brown
solid. Mp: 226–8 8C. Yield 100%. 1H NMR, d (d6-DMSO):
8.85 (s, 3H); 6.48 (d, 6H, J¼2 Hz); 6.33 (t, 3H, J¼2H);
5.30 (s, 6H); 3.17 (s, 6H). 13C NMR, d (d6-DMSO): 165.1,
159.6, 138.8, 134.7, 132.4, 107.2, 103.3 and 67.8. MS
(FABþ), m/z: 576 (Mþ).
1
carbon tetrachloride. Mp: 152–3 8C. Yield 70%. H NMR,
d: 7.49 and 7.47 (d, 12H, A2 of A2B2 system, J¼8 Hz); 7.27
and 7.25 (d, 12H, B2 of A2B2 system, J¼8 Hz); 6.63 (d, 6H,
J¼2 Hz); 6.49 (t, 3H, J¼2 Hz); 6.20 (s, 3H); 4.97 (s, 12H);
4.93 (s, 6H). 13C NMR, d: 160.4, 159.8, 139.3, 135.6,
131.7, 129.1, 122.0, 106.4, 101.5, 94.8, 69.8 and 69.3. MS
(L-SIMS), m/z: 1506.89 (MþHþ6)þ(100), 1508.89
(MþHþ8)þ(85).
3.4.2. 1,3,5-Tris[3,5bis(tert-butyldimethylsilyloxy)benzyl-
oxy]benzene (17). In a previously flamed Schlenk a mixture
of phloroglucinol (88 mg, 0.7 mmol), 7A (1.0 g, 2.8 mmol)
and triphenylphosphine (642 mg, 2.45 mmol) was dissolved
in dry THF (20 mL) under argon atmosphere. A solution of
DEAD (427 mg, 2.45 mmol) in dry THF (5 mL) was added
drop wise and the reaction was stirred at room temperature
overnight. The solvent was evaporated and the crude
product was purified by column chromatography (hexane).
The product was isolated as a white solid. Mp: 74–6 8C.
Yield 35%. 1H NMR, d: 6.52 (d, 6H, J¼2 Hz); 6.28 (t, 3H,
J¼2 Hz); 6.22 (s, 3H); 4.88 (s, 6H); 4.93 (s, 6H); 0.98 (s,
54H); 0.19 (s, 36H). 13C NMR, d: 160.5, 156.6, 138.8,
112.3, 101.4, 95.1, 69.8, 25.7, 18.2 and 24.4. MS (MALDI-
TOF), m/z: 1215.7 (MþNa)þ.
3.3.7. General procedure for dendrimers with ether
connectivity (Williamson conditions). 3B or 5B
(4.2 mmol), 3 (384 mg, 1 mmol), 18-crown-6 (10% mol),
potassium carbonate (580 mg, 4.2 mmol) and acetone
(20 mL) were placed in a round-bottomed flask, and the
reaction mixture was heated at 70 8C for 24 h. The solvent
was evaporated and 20 mL of water were added. The
reaction was extracted with chloroform (20 mL£3).
3.3.8. Tetrakis[(3,5-bis(p-vinylphenylmethyloxy)phenyl-
methyloxyphenyl]methane (18). After column chroma-
tography (chloroform) the pure product was obtained as a
1
pale brown solid. Mp: 78–80 8C. Yield 954 mg, 53%. H
NMR, d: 7.43 and 7.40 (d, 16H, A2 of A2B2 system, J¼
8 Hz); 7.38 and 7.35 (d, 16H, B2 of A2B2 system J¼8 Hz);
6.84 and 6.80 (d, 8H, A2 of A2B2 system, J¼8 Hz), from
6.72–6.60 (m, 24H); 6.53 (t, 4H, J¼2 Hz); 5.76 (dd, 8H,
Jgem¼1 Hz, Jtrans¼18 Hz); 5.26 (dd, 8H, Jgem¼1 Hz,
Jcis¼11 Hz); 5.02 (s, 16H); 4.95 (s, 8H). 13C NMR, d:
159.8, 156.5, 139.9, 139.6, 137.3, 136.3, 136.0, 131.7,
127.6, 126.3, 114.1, 113.8, 108.2, 102.2, 70.6, 70.0 and
61.6. MS (MALDI-TOF), m/z: 1823.8 (MþNa)þ.
Acknowledgements
This work was supported by the Spanish Ministerio de
´
Ciencia y Tecnologıa (Project BQU2002-1327). J. T. is
indebted to the Spanish Ministerio de Educacion y Ciencia
´
for a grant.
3.3.9. Tetrakis[(3,5-bis(p-vinylphenylmethyloxy-p-phenyl-
oxyethyleneoxyethyleneoxy)phenylmethyloxyphenyl]
methane (19). After column chromatography (chloroform)
the pure product was obtained as a pale yellow solid. Mp:
62–4 8C. Yield 1.4 g, 43%. H NMR, d: 7.44 and 7.40
(d, 16H, A2 of A2B2 system, J¼8 Hz); 7.38 and 7.34 (d,
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