Facile Synthesis of Polyamide Dendrimers from Unprotected AB2 Building Blocks

Article abstract of DOI:10.1021/ol035595s

(Equation presented) A fast, inexpensive, and highly efficient synthesis of aromatic polyamide dendrimers without the need for protection and deprotection steps has been developed. Dendrons and third-generation polyamide dendrimers were easily prepared by

Full text of DOI:10.1021/ol035595s

ORGANIC
LETTERS
2003
Vol. 5, No. 22
4159-4161
Facile Synthesis of Polyamide
Dendrimers from Unprotected AB2
Building Blocks
Isao Washio, Yuji Shibasaki, and Mitsuru Ueda*
Department of Organic and Polymeric Materials, Graduate School of Science and
Engineering, Tokyo Institute of Technology, 2-12-1, O-okayama, Meguro-ku,
Tokyo 152-8552, Japan
mueda@polymer.titech.ac.jp
Received August 25, 2003
ABSTRACT
A fast, inexpensive, and highly efficient synthesis of aromatic polyamide dendrimers without the need for protection and deprotection steps
has been developed. Dendrons and third-generation polyamide dendrimers were easily prepared by a convergent approach involving activation
of a focal point with thionyl chloride, followed by condensation with unprotected AB2 building blocks.
Dendrimers present a palette of unique properties, with
applications in fields ranging from chemistry, catalysis, and
material science to biology. However, syntheses of these
macromolecules are tedious and provide poor yields due to
the large number of steps involving repetitive protection-
deprotection and purification processes in each generation.
Although several groups have reported shortened syntheses1
using double-stage, double-exponential growth, hypermono-
mer, and orthogonal coupling strategies, no effective methods
have been developed for synthesizing polyamide dendrimers.2
convergent method without repetitive protection-deprotec-
tion procedures, involving direct condensation of a carboxylic
acid and an unprotected AB2 building block, 3,5-bis(4-
aminophenoxy)benzoic acid (1), using the condensing agent
diphenyl (2,3-dihydro-2-thioxo-3-benzoxazolyl)phosphonate
(DBOP).3 DBOP is very useful for producing amides and
esters from carboxylic acids and amines or phenols in
quantitative yields;4 however, DBOP is an expensive reagent,
especially for industrial large-scale synthetic use. Therefore,
(2) (a) Miller, T. M.; Neenan, T. X. Chem. Mater. 1990, 2, 346. (b)
Bayliff, P. M.; Feast, W. J.; Parker, D. Polym. Bull. 1992, 265. (c) Backson,
S. C. E.; Bayliff, P. M.; Feast, W. J.; Kenwright, A. M.; Parker, D.; Richards,
R. W. Macromol. Symp. 1994, 77, 1. (d) Ishida, Y.; Jikei, M.; Kakimoto,
M. Macromolecules 2000, 33, 3202. (e) Rannard, S. P.; Davis, N. J.;
McFarland, H. Polym Int. 2000, 49, 1002.
(3) Okazaki, M.; Washio, I.; Shibasaki, Y.; Ueda, M. J. Am. Chem. Soc.
2003, 125, 8120.
(4) (a) Ueda, M.; Kameyama, A.; Hashimoto, K. Macromolecules 1988,
21, 19. (b) Okazaki, M.; Hyakawa, T.; Ueda, M.; Takeuchi, K.; Asai, M.
J. Polym. Sci. Polym. Part A: Polym. Chem. 2001, 38, 78.
Recently, we reported the rapid synthesis of a perfectly
branched third-generation polyamide dendrimer by the
(1) For reviews, see, for example: (a) Dendrimers and Dendrons,
Concepts, Syntheses, Applications; Newcome, G. R., Moorfield, C. N.,
Vo¨gtle, F., Eds.; VCH: Weinheim, Germany, 2001. (b) Dendrimer and
Other Dendritic Polymers; Fre´chet, J. M. J., Tomalia, D. A., Eds.; VCH:
Weinheim, Germany, 2002. (c) Grayson, M. S.; Fre´chet, J. M. J. Chem.
ReV. 2001, 101, 3819.
10.1021/ol035595s CCC: $25.00 © 2003 American Chemical Society
Published on Web 10/09/2003

carboxylic acids by thionyl chloride and (2) condensation
with 1. The molar ratio of thionyl chloride to the carboxyl
group is very important for quantitative activation and
prevention of unfavorable reactions such as self-condensation
of 1 and reaction of thionyl chloride with amines. Thus, the
reaction of 4-t-butylbenzoic acid with 4-phenoxy aniline was
performed to determine the optimum molar ratio of thionyl
chloride and a carboxylic acid in 1-methyl-2-pyrrolidinone
(NMP). The reaction of 1.04 equiv of thionyl chloride to
4-tert-butyl benzoic acid provided the corresponding amide
in quantitative yield. Then, the condensation of 4-tert-butyl-
benzoic acid with 1 in the presence of 1.04 equiv of thionyl
chloride to the carboxylic acid was employed. Quantitative
formation of the corresponding amide was observed.
Scheme 1. Synthesis of Dendrons
The syntheses of G1, G2, and G3 dendrons are shown in
Scheme 1. Dendron 1 was reacted with acetyl chloride to
yield G1 dendron 2 in 98% yield after addition of the solution
into water. The structure of 2 was characterized by IR, NMR,
and elemental analyses. The IR spectrum of 2 showed strong
absorptions at 1697 and 1658 cm-1, characteristic of the
CdO stretching of carboxyl acid and amide groups, respec-
Scheme 2. G3 Dendrimer Synthesis
finding a substitute for DBOP is important to expand the
scope of this dendrimer synthesis.
An inexpensive, commercially available reagent, thionyl
chloride, is well-known as an activating agent for preparation
of amides as well as acid chlorides from carboxylic acids.5
Previously, we reported that thionyl chloride is effective for
polyamide6 and polyester7 syntheses, after which no difficult
purification procedures were necessary because the only
byproducts were gases such as SO2 and HCl.
Here, we present a facile synthesis of a perfectly branched
third-generation polyamide dendrimer from unprotected 1
as an AB2-building block by the convergent method using
thionyl chloride as a versatile and common condensing
reagent.
The coupling reaction for dendron synthesis was carried
out by a two-step method involving (1) activation of
(5) Normant, J. F.; Deshayes, H. Bull. Soc. Chim. Fr. 1972, 2854.
(6) Ueda, M.; Aoyama, S.; Konno, M.; Imai, Y. Makromol. Chem. 1978,
179, 2089.
(7) Imai, Y.; Aoyama, S.; Nguyen, T. Q.; Ueda, M. Makromol. Chem.
Rapid Commun. 1980, 1, 655.
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Org. Lett., Vol. 5, No. 22, 2003

tively. Further evidence of the formation and isolation of 2
1
was obtained in the H NMR spectrum.
G2 (3) and G3 (4) dendrons were prepared by the two-
step method as mentioned above, in which thionyl chloride
was employed as the condensing agent. The activation time
of the carboxylic acid and the time for condensation were
independently set depending on the dendron as shown in
Scheme 1. In the case of G3 dendron synthesis, 2.0 equiv of
thionyl chloride with respect to the G2 dendron was required.
We assume that thionyl chloride decomposed during activa-
tion because of the hygroscopic nature of the amides in the
G2 dendron. When the same reaction was conducted after
drying 3 at 150 °C under reduced pressure, 1.1 equiv of
thionyl chloride was sufficient to obtain 4.
Each dendron was purified simply by reprecipitation to
remove the parent dendron. G2 and G3 dendrons were
isolated by reprecipitation with MeOH/water and EtOH in
92 and 72% yields, respectively, followed by characterization
by IR, NMR, MALDI-TOF MS, and elemental analyses. The
MALDI-TOF MS spectra of 3 and 4 showed the expected
[M + Na]+ peaks at 1163.0 and 2606.3, respectively. These
findings clearly indicate the successful formation and isola-
tion of the desired dendrons. The elemental analysis showed
the contamination of a small amount of water in these
dendrons even after the high-temperature dehydration under
the reduced pressure. Thus, the accurate yields of G2 and
G3 were determined by elemental analysis.
Figure 1. MALDI-TOF MS spectrum of the G3 dendrimer (5).
G3 polyamide dendrimer 5 (calcd mass 5329.39). A single
signal was observed at M/Z ([M + Na]+) ) 5354.3,
indicating the formation of the G3 dendrimer.
In conclusion, we have demonstrated a simple and highly
efficient convergent approach for the synthesis of aromatic
polyamide dendrimers using the inexpensive reagent thionyl
chloride. In this method, the purification of each dendron
and dendrimers requires only precipitation. The MALDI-
TOF MS spectra supported the formation of the G2 and G3
dendrons and the G3 dendrimer. The methodology allows
the large-scale and facile synthesis of dendrimers.
Finally, a dumbbell-shaped dendrimer (5) was synthesized
from 4 and 4,4′-oxydianiline (Scheme 2). The reaction of 4
with 4,4′-oxydianiline was performed using 1.50 equiv of
thionyl chloride with respect to the G3 dendron. The reaction
mixture was poured into water and the precipitate collected
and dried. The crude product was dissolved in N,N-
dimethylformamide and the resulting solution reprecipitated
with THF, giving dendrimer 5 in 74% yield. This value was
also calculated on the basis of water contamination deter-
mined by elemental analysis. IR, NMR, MALDI-TOF MS,
and elemental analyses were performed for the characteriza-
tion of 5. Figure 1 shows the MALDI-TOF MS spectrum of
Acknowledgment. This work was financially supported
by the New Energy and Industrial Technology Development
Organization (NEDO) for the project of nanostructure
polymers.
Supporting Information Available: Synthetic details and
the characterization of each dendron and the G3 dendrimer.
This material is available free of charge via the Internet at
http://pubs.acs.org.
OL035595S
Org. Lett., Vol. 5, No. 22, 2003
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