Divergent approach for synthesis and terminal modifications of dendritic polyphenylazomethines

Article abstract of DOI:10.1021/ol701925a

(Chemical Equation Presented) In the past, dendritic polyphenylazomethines (DPA) have been synthesized via the convergent method. However, the convergent method has problems such as difficult terminal-group modifications and an increased number of steps.

Full text of DOI:10.1021/ol701925a

ORGANIC
LETTERS
2007
Vol. 9, No. 25
5151-5154
Divergent Approach for Synthesis and
Terminal Modifications of Dendritic
Polyphenylazomethines
Kensaku Takanashi and Kimihisa Yamamoto*
Department of Chemistry, Faculty of Science & Technology, Keio UniVersity,
Yokohama 223-8522, Japan
yamamoto@chem.keio.ac.jp
Received August 8, 2007
ABSTRACT
In the past, dendritic polyphenylazomethines (DPA) have been synthesized via the convergent method. However, the convergent method has
problems such as difficult terminal-group modifications and an increased number of steps. Therefore, we synthesized the terminal-protected
DPA to construct the dendritic structure via the divergent method. The combination of the convergent method and the divergent method
easily achieved the rapid synthesis of a higher generation dendrimer. Furthermore, we succeeded in the synthesis of the water-soluble PEG-
DPA via the divergent method using the ester-DPA.
Dendrimers have a single molecular weight and three-
dimensional spreading structure in which the density of the
branches increases radially outward.1 On the basis of these
properties, dendrimers have potential use in drug delivery
systems,2 electronic materials,3 catalysts,4 molecular recogni-
tions,5 and charge separation systems.6 Dendritic polyphe-
nylazomethines (DPA) have π-conjugated rigid backbones,
a basicity gradient from the core imines to the terminal
imines, and a stepwise complexation property.7 Due to these
properties, DPA was used as the hole-transport material for
OLEDs,8 oxidative polymerization catalyst for fluorophe-
nols,9 solar cells,10 and self-assemblies.11
DPA has such unique properties, but the end-group
modification has rarely been done12,13 because, to date, DPA
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10.1021/ol701925a CCC: $37.00
© 2007 American Chemical Society
Published on Web 11/13/2007

has only been constructed using the convergent method. The
end-group modification with complete control enables the
further addition of the functions for DPA and extends the
applications of DPA.
group had to resist harsh, dehydrating conditions such as
TiCl4 (Lewis acid) in the presence of DABCO (base) and
be removed without breaking the imines. We investigated
various protecting groups and found that the amide group
has such properties. We investigated the effect of varying
the amide substituents on the stability and solubility (Figure
2). Stability during silica gel chromatography decreased when
In most cases, dendrimers are constructed by the conver-
gent method or the divergent method only. The convergent
method forms a dendrimer from outside to inside. With this
method, it is easy to change the core group but difficult to
change the end group. On the other hand, with the divergent
method, it is easy to change the end group but difficult to
change the core group. Furthermore, stepwise synthesis only
using the convergent method or the divergent method
requires a significant number of steps and a long time.
Therefore, a combination of the divergent method and the
convergent method called the double-stage convergent
method is a good approach to alleviate these problems
(Figure 1).14,15
Figure 2. The effect of varying the amide substituents on the
stability and solubility. When R is an electron-rich group, the amide
becomes too stable for hydrolysis and insoluble in PhCl. On the
other hand, when R is an electron-poor group, the amide becomes
unstable for hydrolysis and soluble in PhCl. As a result, the
trichloroacetamide (R ) CCl3) has the appropriate solubility and
stability.
the amide was substituted with a CF3, whereas a CH3
substituent resulted in decreased solubility in PhCl and was
also difficult to remove. As a result, the best approach during
the synthesis of DPA was to protect the amine group as a
trichloroacetamide.
Amido-DPA G1 was synthesized by the dehydration of
p-phenylenediamine and 4,4′-trichloroacetoamidobenzophe-
none (Scheme 1). Under basic conditions, amido-DPA G1
Figure 1. Synthesis of dendrimer via the double-stage convergent
method. The divergent method constructs the inner frame, and the
convergent method constructs the outer frame. The combination
of the divergent method and the convergent method allowed the
easy and rapid synthesis of dendrimers with various types of cores,
terminal groups, and generations.
We now report the synthesis of DPA using the double-
stage convergent method and the synthesis of the water-
soluble DPA by the divergent method.
Scheme 1. Synthesis of Amido-DPA G1 and Amino-DPA G1
An appropriate protecting group for the amine was
required for the divergent synthesis of DPA. The protecting
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was hydrolyzed to form amino-DPA G1. The obtained
amino-DPA G1 was reacted with DPA dendron G3 to
synthesize DPA G4 (Figure 3). The MALDI TOF MS
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Org. Lett., Vol. 9, No. 25, 2007

spectrum of the reaction mixture showed the generation of
DPA G4 via DPA dendron G3. This method was also used
various end-group modifications are possible. Because the
amide group is a good protecting group for such conditions,
the ester group was also expected to be successful for this
purpose. The ester is a protecting group for carboxylic acid
and hydroxyl groups. These groups are useful for the end-
group modification. In these, we selected the phenolic
hydroxyl group because of its reactivity toward the etheration
under mild conditions and the stability of the formed ether
bond. Therefore, we used the ester as a protecting group for
the phenolic hydroxyl group and performed the end-group
modification through the etheration of the phenolic hydroxyl
group on the terminal of the DPA.
We selected a benzoyl ester as the protecting group.
First, 4,4′-dihydroxybenzophenone was reacted with benzoyl
chloride to obtain 4,4′-dibenzoyloxybenzophenone (Scheme
2). This ester benzophenone and 4,4′-diaminodiphenyl-
methane were dehydrated to form the precursor of ester-
DPA dendron G2. The precursor was then oxidized to ester-
DPA dendron G2 by KMnO4 in the presence of TBABr. The
obtained ester-DPA dendron G2 was reacted with amino-
DPA G1 to form ester-DPA G3. Furthermore, the ester-DPA
G3 was hydrolyzed under basic conditions to form OH-DPA
G3.
Figure 3. Synthesis of DPA G4 via the combination of amino-
DPA G1 and DPA dendron G3.
for the synthesis of DPA dendrons (see Supporting Informa-
tion).15 For the DPA synthesis, this combination of the
divergent method and the convergent method is a good
approach because of the separate construction of DPA from
the inside and outside and the control of the number of
reaction sites.
Initially, for the end-group modification of DPA, only the
substituents that were resistant to dehydrating and oxidizing
conditions were used. Furthermore, the convergent approach
prevents easy modification of the end group. However, if
the modification was performed as in the divergent approach,
As various functions were possible by modification, we
tried the synthesis of the water-soluble DPA. For addition
of the hydrophilic property to DPA, a sulfonic acid
salt, carboxylic acid salt, ammonium salt, and polyethyl-
eneglycol (PEG) were considered. For these salts, we
used PEG as an additional modification group because it
makes handling of the DPA easier during reaction and
purification.
To obtain a sufficient water solubility, we used dodeca-
ethyleneglycol. First, the PEG was monotosylated using
Scheme 2. Synthesis of Ester-DPA G3 via Amino-DPA G1 and Ester-DPA Dendron G2 and Synthesis of PEG-DPA G3 via Ester-
and OH-DPA G3
Org. Lett., Vol. 9, No. 25, 2007
5153

G3 as an oil. The MALDI TOF MS spectrum showed a
single peak, and the observed molecular weight agreed with
the calculated one (Figure 4a). The water solubility of the
PEG-DPA G3 was also confirmed (Figure 4b). We are
studying the applications of the water-soluble dendrimer for
drug delivery systems, MRI, self-assembling, and organic
molecules and metal ion assembling.
In conclusion, we synthesized DPA by a combination of
the divergent method and the convergent method. This
combination allowed an easy and rapid synthesis of DPA.
Further, we tried the end-group modification by the divergent
method. The water-soluble PEG-DPA was synthesized from
the ester-DPA G3.
Acknowledgment. This work was partially supported by
the CREST project from JST and Grants-in-Aid for Scientific
Research (Nos. 19205020 and 178146) from Ministry of
Education, Culture, Sports, Science and Technology.
Note Added after ASAP Publication. Reference 7c was
added shortly after ASAP publication on November 13, 2007.
Supporting Information Available: Detailed experi-
mental procedures and characterization data of the dendrons
and dendrimers. This material is available free of charge via
the Internet at http://pubs.acs.org.
Figure 4. (a) MALDI TOF MS spectrum of PEG-DPA G3 and
(b) PEG-DPA G3 dissolved in water.
OL701925A
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Ag2O (see Supporting Information).16 This monotosylated
PEG was reacted with the OH-DPA G3 to obtain PEG-DPA
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