Synthesis, characterization, and 1H NMR self-diffusion studies of dendritic aliphatic polyesters based on 2,2-bis(hydroxymethyl)propionic acid and 1,1,1-tris(hydroxyphenyl)ethane

Article abstract of DOI:10.1021/ja954171t

Dendritic aliphatic polyesters of one, two, three, and four generations (M(w): 906, 1856, 3754, and 7549 g/mol) were synthesized in the convergent fashion, using 2,2-bis(hydroxymethyl)propionic acid as building block and 1,1,1-tris(hydroxyphenyl)ethane as

Full text of DOI:10.1021/ja954171t

6388
J. Am. Chem. Soc. 1996, 118, 6388-6395
1
Synthesis, Characterization, and H NMR Self-Diffusion Studies
of Dendritic Aliphatic Polyesters Based on
2,2-Bis(hydroxymethyl)propionic Acid and
1,1,1-Tris(hydroxyphenyl)ethane
Henrik Ihre,† Anders Hult,*,† and Erik So1derlind‡
Contribution from the Department of Polymer Technology and Department of Chemistry, Physical
Chemistry, Royal Institute of Technology, S-100 44 Stockholm, Sweden
ReceiVed December 11, 1995X
Abstract: Dendritic aliphatic polyesters of one, two, three, and four generations (Mw: 906, 1856, 3754, and 7549
g/mol) were synthesized in the convergent fashion, using 2,2-bis(hydroxymethyl)propionic acid as building block
and 1,1,1-tris(hydroxyphenyl)ethane as core molecule. Dendrons of one to four generations were synthesized from
the building block and in a final step coupled to the core molecule. The focal point of the dendrons was protected
by a benzyl ester group and deprotected by catalytic hydrogenolysis. The esterifications were performed by conversion
of the acid into the corresponding acid chloride and followed by reaction of the acid chloride with the hydroxyl
1
groups in the presence of triethylamine and dimethylaminopyridine. The simplicity of the H-NMR and 13C-NMR
spectras and elemental analyses suggest that pure and monodisperse dendrimers were obtained. Molecular self-
diffusion studies of first, second, third, and fourth generation dendrimers were performed, in chloroform, using pulsed-
field spin echo 1H NMR spectroscopy. The self-diffusion coefficients were calculated with the standard form of the
Stejskal-Tanner equation. The effective radii of the dendrimers were estimated from the diffusion coefficients by
assuming a spherical geometry for all dendrimers. The radii obtained were 7.8, 10.3, 12.6, and 17.1 Å for the first,
second, third, and fourth generation dendrimer, respectively.
Introduction
coupled to the polyfunctional core molecule to form a dendrimer
of a certain generation. The great advantage with the convergent
growth approach is that each step in the synthesis of the final
dendritic structure can be very well controlled, since fewer
functional groups are involved in each reaction. Furthermore
the large differences in molecular weight between products and
byproducts in the convergent approach makes purification
simpler.
Dendrimers,1-3 arborols,4,5 and cascade compounds6 all
represent a new type of polymers which is characterized by a
highly branched, well-defined structure with an origin in a
central branching point. Hyperbranched polymers7 resemble
dendrimers with the exception that they contain not fully
branched ABx monomers. Properties of dendrimers and hy-
perbranched polymers have been compared by Freche´t et al.8
Divergent and convergent growth are two different stepwise
procedures in the synthesis of well-defined dendritic structures.
In the divergent growth, successfully employed by, e.g., Tomalia
et al.,1,2 Newkome et al.,4,5 and Meijer et al.,3 the ABx
monomers are added layer by layer, i.e., generation by genera-
tion, around the core molecule. In the convergent growth
approach, developed by Hawker and Fre´chet,9-11 dendrons are
initially synthesized from the ABx monomer and in a final step
1
From H NMR self-diffusion measurements the molecular
diffusion coefficients can be calculated. Since the diffusion
coefficients depend on the size and geometry of the diffusion
molecules, this method may be used as a tool for estimating
the molecular size. This method has previously been utilized
in a large number of studies of surfactant aggregates in different
solvents.12 However, it has so far only found limited use in
the area of dendritic polymers.13
This paper deals with the convergent synthesis and charac-
terization of dendritic aliphatic polyesters based on 2,2-bis-
(hydroxymethyl)propionic acid (bis-MPA) and 1,1,1-tris-
(hydroxyphenyl)ethane as core molecule. The corresponding
hyperbranched system based on bis-MPA with an aliphatic core
molecule has been synthesized and well characterized.14,15 In
a future study we hope to compare hyperbranched polymers
and dendrimers, based on bis-MPA as a building block. In this
* To whom all correspondence should be addressed.
† Department of Polymer Technology.
‡ Department of Chemistry.
X Abstract published in AdVance ACS Abstracts, June 15, 1996.
(1) Tomalia, D. A.; Baker, H.; Dewald, J. R.; Hall, M.; Kallos, G.; Martin,
S.; Roeck, J.; Ryder, J.; Smith, P. Polym. J. (Tokyo) 1985, 17, 117.
(2) Tomalia, D. A.; Naylor, A. M.; Goddard, W. A. Angw. Chem., Int.
Ed. Engl. 1990, 29, 138.
(3) Brabender, E. M. M.; Meijer, E. W. Angw. Chem., Int. Ed. Engl.
1993, 32, 1308.
(4) Newkome, G. R.; Yao, Z.-q.; Baker, G. R.; Gupta, V. K. J. Org.
Chem. 1985, 50, 2003.
1
work we also present H NMR self-diffusion studies that not
only yield the diffusion coefficients and estimations of the
(5) Newkome, G. R.; Moorfield, C. N.; Baker, G. R. Aldrich. Acta 1992,
25, 31.
(6) Buhlein, E.; Wehner, W.; Vo¨gtle, F. Synthesis 1978, 155.
(7) Kim, Y. H.; Webster, O. W. Macromolecules 1992, 25, 5561.
(8) Wooley, K. L.; Freche´t, J. M. J.; Hawker, C. J. Polymer 1994, 35,
4489.
(9) Hawker, C. J.; Fre´chet, J. M. J. J. Am. Chem. Soc. 1990, 112, 7638.
(10) Fre´chet, J. M. J.; Hawker, C. J.; Wooley, K. L. J.M.S-Pure Appl.
Chem. 1994, A31(11), 1627.
(12) So¨derman, O.; Stilbs, P. Prog Nucl. Magn. Reson. Spectrosc. 1994,
26, 445.
(13) Young, J. K.; Baker, G. R.; Newkome, G. R.; Morris, K. F.; Johnson,
C. S., Jr. Macromolecules 1994, 27, 3464.
(14) Malmstro¨m, E.; Johansson, M.; Hult, A. Macromolecules 1995, 28,
1698.
(15) Malmstro¨m, E.; Liu, F.; Boyd, R. H.; Hult, A.; Gedde, U. W.
Polymer Bulletin 1994, 32, 679-685.
(11) Hawker, C. J.; Fre´chet, J. M. J. J. Am. Chem. Soc. 1992, 115, 8405.
S0002-7863(95)04171-0 CCC: $12.00 © 1996 American Chemical Society

Synthesis of Dendritic Aliphatic Polyesters
J. Am. Chem. Soc., Vol. 118, No. 27, 1996 6389
Table 1. SEC- and Diffusion NMR Data of Dendritic Polyesters
13-16
molecular sizes but also indicate that the synthesized dendrimers
are monodisperse.
Mw (calcd) Mw (SEC) Mn (SEC)
D × 1012 radius
dendrimer (g/mol)
(g/mol)
(g/mol)
â
(m2/s)
(Å)
Results and Discussion
13
14
15
16
906
1855
3754
7549
1154
1870
3057
4660
1119
1803
2893
4438
1.00
1.00
1.00
1.00
519
392
321
236
7.8
10.3
12.6
17.1
Synthesis. Bis-MPA was chosen as the AB2 monomer in
the synthesis of the dendritic aliphatic polyesters 13, 14, 15,
and 16. In the convergent growth approach dendrons of certain
generations were initially synthesized. In a final step these
dendrons were coupled to the polyfunctional core molecule. To
get an acceptable overall yield it is important that all reactions
such as coupling, protection, and deprotection are selective and
proceed in high yields since a large number of steps are involved
in our design of the final dendrimers.
yields of 93, 89, 74, and 30% in the final coupling step. In the
synthesis of the fourth generation dendron and in the coupling
of the third and fourth generation dendrons to the core molecule
yields start to decrease significantly, probably due to restricted
steric accessibility of the hydroxyls.
In the synthetic route selected involving bis-MPA (Scheme
1), its hydroxyl groups were protected or deactivated by
conversion into the corresponding acetate esters. The diacetate
ester of bis-MPA 1 was prepared by reacting bis-MPA with
acetyl chloride in the presence of triethylamine (TEA) and
dimethylaminopyridine (DMAP) in CH2Cl2. Without DMAP
significant amounts of monoacetylated bis-MPA and acetic acid
were formed. The acid group in bis MPA was protected by a
benzyl ester group. The benzyl ester of bis-MPA 2 was
prepared by first forming the potassium salt of bis-MPA and in
a second step reacting the salt with benzyl bromide. The benzyl
ester group could be removed selectively in very high yields
by catalytic hydrogenolysis16 without affecting the ester bonds
formed in the convergent growth. Hydrogenolysis was per-
formed at atmospheric pressure using Pd/C (10%) as catalyst.
Deprotection was complete in high yields within 30 min. All
esterifications were performed by first converting the acid into
the corresponding acid chloride. All acid chlorides were
prepared using 2 equiv oxalylchloride and a catalytic amount
of DMF in CH2Cl2. The excess of oxalyl chloride was removed
on the rotary evaporator by a stripping procedure with chloro-
form. The ester bond was then formed by reacting a small
excess of the acid chloride with the hydroxyl groups in the
presence of TEA and a catalytic amount of DMAP in dry CH2-
Cl2. The use of pyridine instead of TEA resulted in low yields
and formation of side products. The use of the same core
molecule as in the previously studied hyperbranched system14
based on bis-MPA 2-ethyl-2-(hydroxymethyl)-1,3-propanediol
(TMP) resulted in low yields due to restricted steric accessibility
to the hydroxyls in the final coupling step of the dendrons. The
lack of UV-activity, aromatic structures, or functional groups
allowing easy monitoring made the use of thin layer chroma-
tography difficult. These problems were overcome by the use
of the less sterically hindred and UV-active 1,1,1-tris(hydroxy-
phenyl)ethane as core molecule.9
Characterization of the Dendrimers
General Characterization. The techniques used for the
characterization of dendrimers 13, 14, 15, and 16 were 1H NMR,
13C NMR, size exclusion chromatography (SEC), elemental
analyses, and pulsed field-gradient spin echo (PGSE) 1H NMR.
1
The simplicity of the H NMR and 13C NMR spectra is an
indication of the high purity of dendrimers 13-16. Different
generations may readily be seen in the H NMR spectra of
1
dendrimers 13-16 (Figure 1). The resonances from the methyl
groups, 1.42, 1.28, 1.22, and 1.19 ppm in dendrimer 16 (A, B,
C and D), all result in singlets but of significantly different
chemical shifts reflecting the generation number. The reso-
nances from the methylene groups (F, G, and H) are well
separated up to the third generation. In the fourth generation
dendrimer (16), the resonances from the second and third
generation methylene groups (G and H) become inseparable.
The same pattern can be seen for the quaternary carbons (f, g,
h, and i) and the carbonyl carbons (a, b, c, and d) in the 13C
NMR spectra (Figure 2). The symmetry of the two doublets
emanating from the core molecule at 6.96-7.13 ppm (K and
L) indicates a fully substituted core molecule. When only one
or two dendrons were coupled to the core molecule, no
symmetry was observed.
Since no adequate SEC standards are available linear
polystyrene was used as standard. As expected, the molecular
weights determined were not in agreement with the theoretical
molecular weights as seen in Table 1. This is explained by
differences in the hydrodynamic volume of linear polystyrene
standards and the synthesized dendritic polyesters. SEC
analyses showed polydispersity values (Mw/Mn) below that of
the linear polystyrene standards (Mw/Mn: 1.02) for the den-
drimers 13-16 (Figure 3).
PGSE-1H NMR Experiments
In the general procedure for the preparation of acid chlorides
1 was converted into the corresponding acid chloride 3 (Scheme
I). Reaction of acid chloride 3 with the protected monomer
unit 2, according to the general esterification procedure gave
the second generation dendron 4 in 82% yield after purification
by liquid chromatography. Removal of the benzyl ester group
by catalytic hydrogenolysis gave the acid 5 in 99% yield. 5
was converted into the acid chloride 6 in 97% yield. The third
(9) and fourth (12) generation dendrons were synthesized in
the same manner.
The pulse sequence employed in the PGSE-1H NMR experi-
ments produces a spin echo with an amplitude I(2τ) (where τ
represents the time between the 90° and 180° pulses). For single
species undergoing Gaussian diffusion, characterized by the self-
diffusion coefficient D, the echo amplitude is described by the
Stejskal-Tanner equation
2
2 2
I(2τ) ) I(0)e-γ g δ (∆-δ/3)D
(1)
Four generations of tridendron dendrimers (13-16) were
obtained by coupling the respective dendrons (3, 6, 9, and 12)
with the core molecule 1,1,1-tris(hydroxyphenyl)ethane accord-
ing to the general esterification procedure (Scheme 2). The final
dendrimers were purified by liquid chromatography eluting with
a hexane/ethyl acetate gradient. The dendritic aliphatic poly-
esters of one, two, three, and four generations were obtained in
In this equation, γ represents the magnetogyric ratio, while δ
denotes the duration of the magnetic field gradient pulses
separated by a time interval ∆ (from leading edge to leading
edge), and g their amplitude. It should be noted that eq 1
assumes that the time interval τ between the pulses is kept
constant throughout the experiment. This was the case in the
present study.

6390 J. Am. Chem. Soc., Vol. 118, No. 27, 1996
Ihre et al.

Synthesis of Dendritic Aliphatic Polyesters
J. Am. Chem. Soc., Vol. 118, No. 27, 1996 6391

6392 J. Am. Chem. Soc., Vol. 118, No. 27, 1996
Ihre et al.
Figure 1. 1H NMR spectra in CDCl3 of dendritic polyesters 13-16.
Figure 2. 13C NMR spectra in CDCl3 of four generations of dendrimers.
In a polydisperse system the observed NMR signal becomes
a superposition of all individual signals, weighted by the volume
fraction of each size of molecule. From the NMR experiment
alone, the functional form of the size distribution function cannot

Synthesis of Dendritic Aliphatic Polyesters
J. Am. Chem. Soc., Vol. 118, No. 27, 1996 6393
are plotted versus γ2g2δ2(∆-δ/3). The linear relationship
obtained for the four samples indicates that they are pure and
monodisperse. This is also confirmed by the parameters
extracted from the fitting procedure, these parameters are given
in Table 1.
For spheres diffusing in a continuous medium of viscosity
η, the relation between the self-diffusion coefficient, D, and
the effective radius of the sphere, R, is given by the Stokes-
Einstein equation
R ) kBT/6πηD
(4)
where kB is the Boltzmann constant and T the temperature.
Equation 4 only holds for diffusion of single species, i.e.,
obstruction effects are not accounted for. Although obstructed
diffusion, i.e., the interactions between the diffusing species,
has been treated before,18 such effects have been neglected here.
For dilute systems, such as those considered here, the interac-
tions between the diffusing species are negligible, and eq 4 may
be used without modifications.
Figure 3. SEC-trace of dendritic polyesters 13-16.
The effective radii of the four dendrimers were calculated
using this equation, and the obtained values are given in Table
1. In these calculations isotope effects on the viscosity of the
solvent were neglected, and the viscosity of protonated chlo-
roform, η(25 °C) ) 0.542 cp was used. As seen in Table 1,
the radius increases from 7.8 to 17.1 Å. for dendrimers 13-16.
These figures correlate well with estimations from molecular
modeling, using SYBYL 6.1, data not presented here. This
study has only been concerned with the sizes of the dendrimers
in one particular solvent, chloroform. However, one may expect
the size of the dendrimers to be dependent on type of solvent,
due to different swelling behavior. Similar effects have
previously been observed in water soluble dendritic macromol-
ecules, whose hydrodynamic radius were shown to be strongly
pH-dependent.13 The NMR diffusion experiment is, therefore,
an excellent tool for the study of swelling of dendrimers in
different solvents, an issue we hope to address in a later study.
Figure 4. Normalized echo intensities, plotted on a logarithmic scale,
of the four different dendrimers, generation 1 (b), 2 (O), 3 (9), and 4
(0), vs γ2g2δ2(∆-δ/3) (see eqs 1 and 2).
Conclusions
The convergent growth approach is useful for the synthesis
of monodisperse dendritic structures. The use of bis-MPA as
a building block results in dendrimers that have simple 1H NMR
and 13C NMR spectra in which the different generations are
easily distinguished.
Molecular self-diffusion studies by pulsed field spin echo 1H
NMR is a convenient method to estimate the hydrodynamic radii
of dendrimers, in solution, of different generations.
be determined. However, given a functional form, its charac-
teristic parameters may be determined. Here it is assumed that
the Kohlrausch-Williams-Watts17 distribution describes the
diffusion coefficients, if there is a distribution of sizes. This
leads to a modified Stejskal-Tanner expression12
2
2
2
â
app
)
I(2τ) ) I(0)e-(γ g δ (∆-δ/3)D
(2)
Experimental Section
In this equation Dapp represents an apparent diffusion coefficient,
while â is a measure of the width of the distribution (0 < â e
1). A mean diffusion coefficient Dmean may be obtained through
the transformation
General Procedures. Bis-MPA was obtained from Perstorp Polyols
AB, Sweden. All other chemicals were purchased from Aldrich and
Merck and used without any further purification. 1H NMR and 13C
NMR spectra were recorded on a Bruker AM 400, at 400 and 100
MHz, respectively, using CDCl3 as solvent. The solvent signals were
used as internal standards for both 1H NMR and 13C NMR recordings.
SEC measurements were performed on a Waters GPC-system using a
solvent delivery system (Model 510), automatic injector (WISP 710B),
and a differential refractometer (Waters 410) as a detector. All
measurements were made at 25 °C with one µ-styragel column (100
Å). THF was used as a solvent at a flow rate of 0.5 mL/min. All
recordings and calculations were made with a Copam PC-501 turbo
unit.
Dmean ) Dapp/(1/â‚Γ(1/â))
(3)
where Γ(1/â) is the γ function of 1/â. For a monodisperse
system â ) 1, and the obtained D becomes the true diffusion
coefficient. By applying a nonlinear least-squares fitting of a
function according to eq 2 to the experimental data, the
parameters I(0), Dapp, and â are easily extracted.
Figure 4 shows the amplitude decays of dendrimers 13-16.
In the figure, the logarithms of the normalized signal intensities
(18) Jo¨nsson, B.; Wennerstro¨m, H.; Nilsson, P.; Linse, P. Colloid Polymer
(16) Vogel, Vogels’s Textbook of Practical Organic Chemistry; Longman
Scientific & Technical: Essex.
(17) Williams, G.; Watts, D. C. Trans. Faraday Soc. 1970, 66, 80.
Sci. 1986, 264, 77.
(19) Callaghan, P. T.; LeGros, M. A.; Pinder, D. N. J. Chem. Phys. 1983,
79, 6376.

6394 J. Am. Chem. Soc., Vol. 118, No. 27, 1996
Ihre et al.
1
The self-diffusion of the dendrimers was studied by means of NMR
spectroscopy, using the well-known pulsed field-gradient spin echo
(PGSE) method.13 The measurements were performed on a JEOL FX-
100 spectrometer, operating at 100 MHz for protons, equipped with a
5-mm 1H probe. An internal field/frequency lock was provided by the
deuterons in the solvent, CDCl3. The gradient driver was homemade
and produced gradients (g) in the range g ≈ 50-70 mT/m. The gradient
strength was calibrated using literature data for water diffusion in 1H2O/
2H2O mixtures.19 The temperature was kept at 25 °C in all experiments.
In this work, each set of experimental data was obtained by varying
the duration of the gradient pulse (δ ) 1-19 ms) keeping the radio
frequency pulse interval (τ ) ∆ ) 140 ms) and the gradient strength
(g) constant. The attenuation of the signal intensities from the terminal
methyl protons (chemical shift, δ ≈ 2.1 ppm) was monitored, and from
a nonlinear least-squares fitting procedure the diffusion coefficient (D)
could be evaluated (from eqs 1-3).
filtrate was evaporated to give 5 as white crystals. 3.3 g (96%); H
NMR (CDCl3) δ 1.24 (s, 6H, -CH3), 1.31 (s, 3H, -CH3), 2.05 (s,
12H, -CH3), 4.20 (s, 8H, -CH2C), 4.28 (s, 4H, -CH2); 13C NMR
(CDCl3) δ 17.46, 17.65, 20.60, 65.38, 170.71, 172.02, 176.44.
[G#2]-COCl [6]. Oxalylchloride (2.90 g, 22.83 mmol) and 6.00 g
(11.23 mmol) of [G#2]-CO2H [5] were reacted according to the general
procedure for acid chloride formation to give 6 as a slightly yellow
1
oil: 6.0 g (97%); H NMR (CDCl3) δ 1.24 (s, 6H, -CH3), 1.40 (s,
3H, -CH3), 2.05 (s, 12H, -CH3), 4.19 (s, 8H, -CH2C), 4.33 (d, 4H,
-CH2C); 13C NMR (CDCl3) δ 17.21, 17.52, 17.63, 20.60, 46.23, 48.39,
48.46, 64.92, 65.41, 65.64, 65.81, 170.65, 171.40, 172.06, 172.26,
173.43, 173.54, 175.96, 176.25.
[G#3]-CO2CH2C6H5 [7]. [G#2]-COCl [6] (5.70 g, 10.32 mmol),
1.10 g (4.91 mmol) of benzyl-2,2-bis(methylol)propionate [2], 0.06 g
(0.5 mmol) of DMAP and 1.2 g (12.3 mmol) of TEA were reacted
according to the general esterification procedure over night to give a
slightly yellow crude product that was purified by liquid chromatog-
raphy on silica gel eluating with hexane gradually increasing to 20:80
hexane/ethyl acetate to give 7 as a colorless viscous oil: 5.3 g (86%);
1H NMR (CDCl3) δ 1.16 (s, 6H, -CH3), 1.22 (s, 12H, -CH3), 1.30 (s,
3H, -CH3), 2.04 (s, 24H, -CH3), 4.18 (m, 24H, -CH2C), 4.26 (q,
4H, -CH2C), 5.16 (s, 2H, -CH2Ar), 7.35 (m, 5H, ArH); 13C NMR
(CDCl3) δ 17.31, 17.46, 17.66, 20.59, 46.24, 46.58, 65.18, 66.09, 67.09,
128.34, 128.46, 128.61, 135.3, 170.31, 171.37, 171.79, 171.94.
[G#3]-CO2H [8]. Pd/C (0.5 g, 10%) and 5.00 g (3.98 mmol) of
[G#3]-CO2CH2C6H5 [4] were reacted according to the general procedure
for removal of the benzyl ester group, approximately 100 mL H2 were
consumed, to give 8 as a colorless viscous oil: 4.55 g (98%); 1H NMR
(CDCl3) δ 1.23 (s, 12H, -CH3), 1.25 (s, 6H, -CH3), 1.33 (s, 3H,
-CH3), 2.06 (s, 24H, -CH3), 4.17 (s, 17H, -CH2C), 4.25 (s, 8H,
-CH2C), 4.29 (m, 4H, -CH2C); 13C NMR (CDCl3) δ 17.35, 17.45,
17.69, 20.63, 46.13, 46.24, 46.66, 65.23, 66.46, 170.71, 171.46, 171.96,
173.57.
2,2-Bis(acetoxymethyl)propionic Acid [1]. Bis-MPA (5.00 g, 37.28
mmol), 9.40 g (93.07 mmol) of TEA and 0.23 g (1.88 mmol) of DMAP
were dissolved in 100 mL of dry CH2Cl2. Acetylchloride (6.20 g, 78.98
mmol) was added drop by drop to the reaction mixture. After 30 min
of stirring, the reaction mixture was extracted with three portions (40
mL) of Na2CO3 (10%). The combined aqueous phase was acidified
with HCl (concentrated) and extracted with three portions (40 mL) of
CH2Cl2. The combined organic phase was dried with MgSO4 and
1
evaporated to give 1 as white crystals: 8.0 (98%); H NMR (CDCl3)
δ 1.29 (s, 3H, -CH3), 2.07 (s, 6H, -CH3), 4.24 (d, 4H, -CH2C); 13
NMR (CDCl3) δ 17.63, 20.60, 45.66, 65.15, 170.84, 177.96.
C
Benzyl-2,2-bis(methylol)propionate [2]. Bis-MPA (9.00 g, 67.11
mmol) and 4.30 g (76.79 mmol) of KOH were dissolved in 50 mL of
DMF. The potassium salt was allowed to form at 100 °C for 1 h.
Benzylbromide (13.80 g, 80.71 mmol) was added. After 15 h of stirring
at 100 °C the DMF was evaporated. The residue was dissolved in
200 mL of diethyl ether and extracted with two portions (50 mL) of
water. The crude product was purified by liquid chromatography on
silica gel eluating with hexane gradually increasing to 20:80 hexane/
ethyl acetate. 2 was obtained as white crystals: 10.0 g (67%); 1H NMR
(CDCl3) δ 1.08 (s, 3H, -CH3), 3.74 (d, 2H, -CH2OH), 3.95 (d, 2H,
-CH2OH), 5.22 (s, 2H, -CH2Ar), 7.36 (m, 5H, ArH); 13C NMR
(CDCl3) δ 17.16, 49.35, 66.64, 67.49, 127.84, 128.28, 128.63, 175.69.
2,2-Bis(acetoxymethyl)propionic Acid Chloride [3] and a General
Procedure for Acid Chloride Formation. Oxalylchloride (6.30 g,
49.61 mmol) was added drop by drop to a solution of 5.40 g (24.77
mmol) of 2,2-bis(acetoxymethyl)propionic acid [1] and 3 drops of DMF
in 40 mL of CH2Cl2. The reaction was allowed to reach completion
for 2 h at 25 °C. The excess oxalylchloride was removed on the rotary
evaporator by a stripping procedure with several portions of chloroform
to give 3 as a yellow oil that was used without any further purifica-
[G#3]-COCl [9]. Oxalylchloride (1.00 g, 7.87 mmol) and 4.30 g
(3.69 mmol) of [G#3]-CO2H [8] were reacted according to the general
procedure for acid chloride formation to give 9 as a slightly yellow
1
oil: 4.30 g (98%); H NMR (CDCl3) δ 1.23 (s, 12H, -CH3), 1.26 (s,
6H, -CH3), 1.45 (s, 3H, -CH3), 2.05 (s, 24H, -CH3), 4.16 (s, 16H,
-CH2C), 4.25 (s, 8H, -CH2C), 4.33 (q, 4H, -CH2C); 13C NMR
(CDCl3) δ 17.31, 17.45, 17.66, 20.60, 46.24, 46.71, 56.03, 65.19, 65.82,
170.34, 170.61, 171.22, 171.45, 171.94, 174.66.
[G#4]-CO2CH2C6H5 [10]. [G#3]-COCl [9] (4.55 g, 3.84 mmol),
287 mg (1.28 mmol) of benzyl-2,2-bis(methylol)propionate [2], 47 mg
(0.38 mmol) of DMAP, and 452 mg (4.48 mmol) of TEA were reacted
according to the general esterification procedure for 24 h to give a
slightly yellow crude product that was purified by liquid chromatog-
raphy on silica gel eluating with hexane gradually increasing to 20:80
hexane/ethyl acetate to give 10 as a colorless viscous oil: 2.60 g (81%);
1H NMR (CDCl3) δ 1.20 (s, 6H, -CH3), 1.22 (s, 24H, -CH3), 1.23 (s,
12H, -CH3), 1.31 (s, 3H, -CH3), 2.08 (s, 48H, -CH3), 4.18 (s, 32H,
-CH2C), 4.20-4.34 (m, 28H, -CH2C), 5.15 (s, 2H, -CH2Ar), 7.35
(m, 5H, ArH); 13C NMR (CDCl3) δ 17.34, 17.50, 17.77, 20.72, 46.31,
46.66, 46.80, 65.14, 65.24, 65.67, 66.53, 67.20, 128.26, 128.55, 128.72,
135.44, 170.46, 171.40, 171.49, 171.83, 172.06.
[G#4]-CO2H [11]. Pd/C (0.26 g, 10%) and 2.60 g (1.03 mmol) of
[G#4]-CO2CH2C6H5 [10] were reacted according to the general
procedure for removal of the benzyl ester group, approximately 25 mL
of H2 were consumed, to give 11 as a colorless viscous oil: 2.48 g
(98.8%); 1H NMR (CDCl3) δ 1.23 (s, 24H, -CH3), 1.25 (s, 12H,
-CH3), 1.29 (s, 6H, -CH3), 1.33 (s, 3H, -CH3), 2.05 (s, 48H, -CH3),
4.19 (s, 32H, -CH2C), 4.21-4.31 (m, 28H, -CH2C); 13C NMR
(CDCl3) δ 17.52, 17.77, 20.74, 46.35, 46.70, 65.31, 65.84, 66.88,
170.59, 171.49, 172.02.
[G#4]-COCl [12]. Oxalylchloride (0.32 g, 2.54 mmol) and 3.08 g
(1.27 mmol) of [G#4]-CO2H [11] were reacted according to the general
procedure for acid chloride formation to give 12 as a slightly yellow
oil: 3.1 g (99.7%); 1H NMR (CDCl3) δ 1.23 (s, 24H, -CH3), 1.25 (s,
12H, -CH3), 1.29 (s, 6H, -CH3), 1.47 (s, 3H, -CH3), 2.04 (s, 48H,
-CH3), 4.17 (s, 32H, -CH2C), 4.21-4.29 (m, 24H, -CH2C), 4.28-
4.40 (m, 4H, -CH2C); 13C NMR (CDCl3) δ 17.34, 17.50, 17.77, 20.72,
46.32, 46.69, 46.75, 65.25, 65.76, 66.25, 170.48, 171.24, 171.49, 172.07,
174.75.
1
tion: 5.8 g (99%); H NMR (CDCl3) δ 1.38 (s, 3H, -CH3), 2.08 (s,
6H, -CH3), 4.28 (s, 4H, CH2C); 13C NMR (CDCl3) δ 17.79, 20.51,
55.77, 64.88, 170.07, 175.06.
[G#2]-CO2CH2C6H5 [4] and a General Esterification Procedure.
2,2-Bis(acetoxymethyl)propionic acid chloride [3] (5.90 g, 24.95 mmol),
diluted in a small amount of dry CH2Cl2, was added drop by drop to
a solution of 2.60 g (11.61 mmol) benzyl-2,2-bis(methylol)propionate
[2], 0.14 g (0.60 mmol) of DMAP, and 3.00 g of (29.70 mmol) of
TEA in 30 mL of dry CH2Cl2 at 0 °C under argon atmosphere. After
stirring at 0 °C for 1 h the temperature was raised to 25 °C, and the
reaction was allowed to reach completion over night. The CH2Cl2 was
evaporated and the dark brown crude product was purified by liquid
chromatography on silica gel eluating with hexane gradually increasing
to 60:40 hexane/ethyl acetate to give 4 as a colorless viscous oil: 5.9
g (82%); 1H NMR (CDCl3) δ 1.16 (s, 6H, -CH3), 1.26 (s, 3H, -CH3),
2.03 (s, 12H, -CH3), 4.14 (s, 8H, -CH2C), 4.27 (d, 4H, -CH2C),
5.15 (s, 2H, -CH2Ar), 7.35 (m, 5H, -ArH); 13C NMR (CDCl3) δ 17.52,
17.62, 46.23, 46.62, 65.22, 65.57, 67.06, 128.32, 128.46, 128.63, 135.31,
170.37, 171.96, 172.01.
[G#2]-CO2H [5] and a General Procedure for Removal of the
Benzyl Ester Group. 0.4 g Pd/C (10%) was added to a solution of
4.00 g (6.41 mmol) of [G#2]-CO2CH2C6H5 [4] in 30 mL of ethyl
acetate. The apparatus for catalytic hydrogenolysis was evacuated from
air and filled with H2. Approximately 170 mL of H2 were consumed.
The Pd/C was filtered off and carefully washed with ethyl acetate. The

Synthesis of Dendritic Aliphatic Polyesters
J. Am. Chem. Soc., Vol. 118, No. 27, 1996 6395
Dendritic Polyester [13]. 2,2-Bis(acetoxymethyl)propionic acid
chloride [3] (2.50 g, 10.57 mmol), 1.03 g (3.36 mmol) of 1,1,1-tris-
(hydroxyphenyl)ethane, 0.06 g (0.50 mmol) of DMAP, and 1.08 g
(10.70 mmol) of TEA in 20 mL of dry CH2Cl2 were reacted according
to the general esterification procedure for 2 h. The dark brown crude
product was purified by liquid chromatography on silica gel eluating
with hexane gradually increasing to 40:60 hexane/ethyl acetate to give
13 as a colorless viscous oil: 2.85 g (93%); 1H NMR (CDCl3) δ 1.40
(s, 9H, -CH3), 2.09 (s, 18H, -CH3), 2.15 (s, 3H, -CH3), 4.35 (s, 12H,
-CH2C), 6.95 (d, 6H, -ArH), 7.08 (d, 6H, -ArH); 13C NMR (CDCl3)
δ 17.93, 20.75, 30.83, 46.70, 51.67, 65.50, 120.78, 129.75, 146.32,
148.73, 170.49, 171.50. Anal. Calcd for C47H54O18: C, 62.24; H, 6.00.
Found: C, 62.15; H, 6.02.
Dendritic Polyester [14]. [G#2]-COCl [6] (1.59 g, 1.88 mmol),
280 mg (0.92 mmol) of 1,1,1-tris(hydroxyphenyl)ethane, 17 mg (0.14
mmol) of DMAP, and 0.32 g (3.21 mmol) of TEA in 10 mL of dry
CH2Cl2 were reacted according to the general esterification procedure
for 4 h. The slightly yellow crude product was purified by liquid
chromatography on silica gel eluating with hexane gradually increasing
to 20:80 hexane/ethyl acetate to give 14 as a colorless viscous oil: 1.51
g (89%); 1H NMR (CDCl3) δ 1.25 (s, 18H, -CH3), 1.41 (s, 9H, -CH3),
2.01 (s, 36H, -CH3), 2.15 (s, 3H, -CH3), 4.21 (s, 24H, -CH2C), 4.41
(s, 12H, -CH2C), 6.97 (d, 6H, -ArH), 7.19 (d, 6H, -ArH); 13C NMR
(CDCl3) δ 17.55, 17.74, 20.57, 30.76, 46.35, 47.00, 51.62, 65.31, 65.60,
120.70, 129.69, 146.32, 148.56, 170.33, 170.75, 172.09. Anal. Calcd
for C89H114O42: C, 57.60; H, 6.19. Found: C, 57.48; H, 6.29.
Dendritic Polyester [15]. ([G#3]-COCl) [9] (1.34 g, 1.14 mmol),
105 mg (0.344 mmol) of 1,1,1-tris(hydroxyphenyl)ethane, 6.3 mg (0.052
mmol) of DMAP, and 122 mg (1.2 mmol) of TEA in 5 mL of dry
CH2Cl2 were reacted according to the general esterification procedure
for 15 h. The slightly yellow crude product was purified by liquid
chromatography on silica gel eluating with hexane gradually increasing
to 20:80 hexane/ethyl acetate to give 15 as a colorless viscous oil: 0.95
g (74%); 1H NMR (CDCl3) δ 1.21 (s, 36H, -CH3), 1.27 (s, 18H,
-CH3), 1.44 (s, 9H, -CH3), 2.04 (s, 72H, -CH3), 2.14 (s, 3H, -CH3),
4.15 (s, 48H, -CH2C), 4.22-4.30 (m, 24H, -CH2C), 4.37-4.39 (m,
12H, -CH2C), 6.98 (d, 6H, ArH), 7.20 (d, 6H, ArH); 13C NMR (CDCl3)
δ 17.44, 17.49, 17.59, 20.53, 30.77, 46.23, 46.65, 46.88, 51.62, 65.18,
66.01, 120.68, 129.68, 146.32, 148.56, 170.24, 170.75, 171.45, 171.95.
Anal. Calcd for C173H234O90: C, 55.36; H, 6.28. Found: C, 55.26;
H, 6.44.
Dendritic Polyester [16]. ([G#4]-COCl) [12] (2.60 g, 1.06 mmol),
81.2 mg (0.265 mmol) of 1,1,1-tris(hydroxyphenyl)ethane, 9.7 mg (0.08
mmol) of DMAP, and 120 mg (1.19 mmol) TEA in 5 mL of dry CH2-
Cl2 were reacted according to the general esterification procedure for
72 h. The slightly yellow crude product was purified by liquid
chromatography on silica gel eluating with hexane gradually increasing
to 20:80 hexane/ethyl acetate to give 16 as a colorless viscous oil: 600
1
mg (30%); H NMR (CDCl3) δ 1.19 (s, 72H, -CH3), 1.22 (s, 36H,
-CH3), 1.28 (s, 18H, -CH3), 1.42 (s, 9H, -CH3), 2.00 (s, 144H,
-CH3), 2.14 (s, 3H, -CH3), 4.15 (s, 96H, -CH2C), 4.21-4.31 (m,
72H, -CH2C), 4.39-4.40 (m, 12H, -CH2C), 6.98 (d, 6H, ArH), 7.10
(d, 6H, ArH); 13C NMR (CDCl3) δ 17.51, 17.74, 20.67, 46.32, 46.67,
47.04, 65.11, 65.23, 65.50, 120.83, 129.79, 146.25, 148.66, 170.38,
170.72, 171.46, 171.52, 172.04. Anal. Calcd for C341H474O186: C,
54.25; H, 6.33. Found: C, 53.97; H, 6.40.
Acknowledgment. Financial support of this work was given
by the Swedish Research Council for Engineering Sciences
(Dnr: 93-1075). Eva Malmstro¨m is gratefully thanked for
valuable discussions.
JA954171T