Cu-catalyzed multicomponent polymerization to synthesize a library of poly(N -sulfonylamidines)

Article abstract of DOI:10.1021/ja312592e

We report a versatile Cu-catalyzed multicomponent polymerization (MCP) technique that enables the synthesis of high-molecular-weight, defect-free poly(N-sulfonylamidines) from monomers of diynes, sulfonyl azides, and diamines. Through a series of optimizations, we discovered that the addition of excess triethylamine and the use of N,N′-dimethylformamide as a solvent are key factors to ensure efficient MCP. Formation of cyclic polyamidines was a side reaction during polymerization, but it was readily controlled by using diynes or diamines with long or rigid moieties. In addition, this polymerization is highly selective for three-component reactions over click reactions. The combination of the above factors enables the synthesis of high-molecular-weight polymers, which was challenging in previous MCPs. All three kinds of monomers (diynes, sulfonyl azides, and diamines) are readily accessible and stable under the reaction conditions, with various monomers undergoing successful polymerization regardless of their steric and electronic properties. Thus, we synthesized various high-molecular-weight, defect-free polyamidines from a broad range of monomers while overcoming the limitations of previous MCPs, such as low conversion and defects in the polymer structures.

Full text of DOI:10.1021/ja312592e

Communication
pubs.acs.org/JACS
Cu-Catalyzed Multicomponent Polymerization To Synthesize a
Library of Poly(N‑sulfonylamidines)
In-Hwan Lee, Hyunseok Kim, and Tae-Lim Choi*
Department of Chemistry, Seoul National University, Seoul 151-747, Korea
*
S Supporting Information
15
ization reactions. Thus, MCP is a promising synthetic strategy
for producing various polyamidine structures. Recently,
Chang’s group reported an efficient Cu-catalyzed 3CR of
alkynes, sulfonyl azides, and amines to generate a library of
small-molecule amidines via Cu-catalyzed azide−alkyne cyclo-
addition (CuAAC) followed by a successive ring-opening
ABSTRACT: We report a versatile Cu-catalyzed multi-
component polymerization (MCP) technique that enables
the synthesis of high-molecular-weight, defect-free poly(N-
sulfonylamidines) from monomers of diynes, sulfonyl
azides, and diamines. Through a series of optimizations, we
discovered that the addition of excess triethylamine and
the use of N,N′-dimethylformamide as a solvent are key
factors to ensure efficient MCP. Formation of cyclic
polyamidines was a side reaction during polymerization,
but it was readily controlled by using diynes or diamines
with long or rigid moieties. In addition, this polymerization
is highly selective for three-component reactions over click
reactions. The combination of the above factors enables
the synthesis of high-molecular-weight polymers, which
was challenging in previous MCPs. All three kinds of
monomers (diynes, sulfonyl azides, and diamines) are
readily accessible and stable under the reaction conditions,
with various monomers undergoing successful polymer-
ization regardless of their steric and electronic properties.
Thus, we synthesized various high-molecular-weight,
defect-free polyamidines from a broad range of monomers
while overcoming the limitations of previous MCPs, such
as low conversion and defects in the polymer structures.
1a,c
process and nucleophilic attack by the amine (Scheme 1).
Scheme 1. Polymerization Scheme for Poly(N-
sulfonylamidine) Synthesis
This synthesis generally resulted in moderate to excellent
isolated product yields (generally 59−95%, with one example
approaching 99%). Furthermore, excellent product selectivity
for the 3CR (>99%) rather than more well-known click
ulticomponent reactions (MCRs) such as the Cu-
reaction leading to the formation of the triazole ring was
1
M
catalyzed three-component reaction (3CR), the Man-
1a,c
observed.
Although click reactions are widely used as a
2
3
3
4
nich reaction, the Passerini reaction, and A coupling, have
received great attention because of their ability to generate
complex molecules economically. MCRs have recently been
introduced into the field of polymer synthesis, and step-growth
polymerization has provided access to various novel materials.
versatile route to two-component step-growth polymeriza-
16
tion, this new MCR has not been applied to polymerization
reactions. Herein we report a versatile synthesis of a library of
poly(N-sulfonylamidines) via a Cu-catalyzed MCP of various
diynes, sulfonyl azides, and diamines. The main advantage of
this method is its high selectivity for the 3CR over the click
reaction, leading to defect-free polymer microstructures.
Furthermore, all three kinds of monomers used are either
readily available or easily accessible and, most importantly,
stable under the reaction conditions employed. Thus, after the
reaction conditions were optimized to maximize the conversion
of the polymerization, 26 well-defined high-molecular-weight
polyamidines were prepared from 26 different monomers,
demonstrating the broad substrate scope of this methodology.
Utilizing the optimal conditions reported by Chang’s group
for the synthesis of small molecules, a model polymerization of
diyne A, p-toluenesulfonyl azide, and N,N′-diisobutyl-1,6-
5
6
7
For instance, polyester, poly(ester−amide), polyether, poly-
8
9
10
(
ester ether ketone), polyurethane, polythiourethane, and
1
1
π-conjugated polymers such as poly(p-phenylenevinylene)
have been synthesized by multicomponent polymerization
MCP). However, many of the previous MCPs are limited by a
(
narrow monomer scope and afford low-molecular-weight
polymers because of low conversion, low solubility, and various
side reactions leading to defects in the polymer structure. Thus,
the development of a new MCP that can generate both high-
molecular-weight and defect-free polymers from a broad range
of monomers would be desirable.
Polyamidines have attracted great attention because of their
1
2
13
potential role as biomaterials, metallic conductors, and
1
4
photosensitive semiconductors. However, their syntheses
have been limited to two-component step-growth polymer-
Received: December 26, 2012
Published: March 1, 2013
©
2013 American Chemical Society
3760
dx.doi.org/10.1021/ja312592e | J. Am. Chem. Soc. 2013, 135, 3760−3763

Journal of the American Chemical Society
Communication
hexanediamine in tetrahydrofuran (THF) was attempted at
improve the polymerization, but excess DIPEA or 2,6-lutidine
(5 equiv) significantly enhanced the conversion (Table S1).
Ultimately, the best additive was found to be 5 equiv of
1a
room temperature. The stoichiometric balance between the
diyne and the diamine was very important because both are
involved in the chain-growth process of the step-growth
polymerization. On the other hand, excess p-toluenesulfonyl
azide (3 equiv) could be used to enhance the conversion of
diyne A without limiting the molecular weight of the resulting
polyamidine. Under these reaction conditions, a significant
amount of precipitate formed during the course of the
polymerization. To increase the solubility, the polymerization
temperature was increased to 50 °C, which resulted in a more
homogeneous reaction mixture. However, the number-average
triethylamine (TEA), which yielded the highest M (10.8 kg/
n
mol; Table 1, entry 5); the absolute molecular weight
determined by multiangle laser light scattering (MALLS) was
much higher (30.8 kg/mol; Table 2, entry 6), suggesting that
the conventional calibration method underestimated M . We
n
speculate that TEA might play two important roles in
enhancing the polymerization conversion. First, protons are
generated in each coupling reaction. In the absence of an
external base such as TEA, the diamine monomers are
protonated to form ammonium salts, which are poor
nucleophiles that do not facilitate conversion. In small-molecule
synthesis, this problem is circumvented by adding excess amine
reagent. However, in step-growth polymerization, where
stoichiometric balance is extremely important, addition of
external bases that do not interfere with the polymerization
would be necessary to regenerate the active nucleophiles.
Second, excess TEA would accelerate the formation of the Cu−
acetylide complex from the Cu(I) catalyst and a terminal alkyne
molecular weight (M ) of the resulting poly(N-sulfonylami-
n
dine) B [2.7 kg/mol as determined by THF size-exclusion
chromatography (SEC) calibrated using polystyrene (PS)
standards] was still low (Table 1, entry 1), prompting further
optimization of the synthetic procedure for highly polar
polyamidines.
Table 1. Optimization of the Model MCP
(
Scheme 1), which in turn should increase the rate of
polymerization and the molecular weights of the final polymers.
1
13
H and C NMR analysis of the final polymer B (Figure S1 in
the SI) confirmed that this MCP is highly selective for the 3CR
over the conventional click reaction. This feature is
indispensable for obtaining high-molecular-weight polymers
because the click reaction between the diyne and the
monofunctionalized sulfonyl azide would produce chain end-
capping groups that would terminate the polymerization
(Scheme 1).
conc
(M)
temp
(°C)
additive
(equiv)
a
entry catalyst solvent
M (PDI)
n
1
2
3
4
5
CuI
THF
DMF
DMF
DMF
DMF
0.5
0.5
0.5
1.0
1.0
50
70
70
70
70
none
2.7 (1.22)
6.2 (1.71)
7.5 (1.92)
7.3 (1.73)
10.8 (2.81)
Under the newly optimized polymerization conditions,
various types of monomers were examined to expand the
substrate scope of this MCP. First, we explored various diynes
containing alkyl, diene, ethylene glycol, and aromatic groups
and found that all of the diynes produced polyamidines with
CuI
none
CuCl
CuCl
CuCl
none
TBTA (0.1)
TEA (5)
a
Determined by THF SEC calibrated using PS standards. M is given
reasonable M ranging from 22 to 64 kg/mol as determined by
n
n
in kg/mol.
MALLS (Table 2, entries 1−6). Initially, the polymerization of
commercially available 1,6-heptadiyne with p-toluenesulfonyl
azide and N,N′-diisobutyl-1,6-hexanediamine was explored, and
a polymer with a relatively lower molecular weight was
obtained (Table 2, entry 1). A closer analysis of the SEC
trace revealed several sharp peaks in the low-molecular-weight
region (Figure 1) even after rigorous purification through
multiple precipitations for complete removal of the monomers.
These low-molecular-weight contaminants were identified as
cyclic dimers and oligomers by MALDI-TOF analysis, which
revealed strong peaks corresponding to the molecular weights
of these cyclic compounds (Figure S2). We hypothesized that
suppressing the cyclization reactions would increase the
molecular weights of the polyamidines, leading us to investigate
how the structure of the alkyne could affect the degree of
cyclization. We observed by SEC analysis that employing a less
flexible diyne containing a diene moiety (1b) or a longer diyne
(1c) as the monomer produced smaller amounts of cyclic
products (Figure 1 and Table 2, entries 2 and 3). Furthermore,
MCP from diynes containing highly rigid moieties such as
phenyl, biphenyl, and naphthyl produced polyamidines with
Toward this goal, solvent screening at high temperatures was
conducted. Polymerization in chloroform, 1,2-dichloroethane
(
DCE), and 1,4-dioxane resulted in unsatisfactory conversion.
However, polymerization at 70 °C in the polar solvent N,N′-
dimethylformamide (DMF) produced B with a doubled M
n
[
Table 1, entries 1 and 2; also see Table S1 in the Supporting
Information (SI)], which was unexpected because DMF has
been reported to be a poor solvent for 3CRs of small
1
d
molecules. It seemed that the highly polar DMF increases the
solubility of the polar poly(N-sulfonylamidines), resulting in
high conversion. With optimized temperature and solvent
conditions, several Cu(I) catalysts were screened because their
counteranions and ligands could affect the catalytic activity in
the MCP. Most catalysts showed good activity, and among
them, CuCl showed the best results (Table 1, entries 2 and 3,
and Table S1). Since the polymer showed excellent solubility in
DMF, the polymerization concentration was increased to 1 M
to facilitate higher conversion. In addition, to enhance the
catalytic activity further, various additives were screened. The
addition of tris(benzyltriazolylmethyl)amine (TBTA), a ligand
higher molecular weights (relative M up to 18 kg/mol and
n
1e
reported to accelerate 3CRs, gave no noticeable improvement
Table 1, entry 4). Next, several amine bases were tried. The
addition of 1 equiv of diisopropylethylamine (DIPEA) did not
absolute Mn up to 64 kg/mol) and significantly smaller
amounts of cyclic compounds (Figure 1 and Table 2, entries 4−
6). Therefore, we could successfully suppress the cyclization
(
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Journal of the American Chemical Society
Communication
Table 2. Synthesis of Various Poly(N-sulfonylamidines)
a
Determined by DMF SEC calibrated using poly(methyl methacrylate) standards (entries 5, 7−14, 16−19, 21−23, 25−26) or THF SEC calibrated
b
using PS standards (entries 1−4, 6, 15, 20, 24). M is given in g/mol. Absolute molecular weights (in g/mol) determined by THF SEC (CHCl
SEC for entries 11 and 12) using a MALLS detector. Isolated yields after precipitation from selected solvents. The absolute molecular weight could
not be obtained because the polymer was not soluble in THF or CHCl3.
n
3
c
d
process by changing the rigidity or length of the diyne
substrate, affording polymers with high molecular weights.
Next, we examined the feasibility of using different sulfonyl
azides. At first, various phenylsulfonyl azides containing
electron-donating groups (−OMe, −NHCOMe), electron-
withdrawing groups (−CF , −NO ), or a sterically hindered
group (−iPr) at various positions on the aromatic ring were
tested. Surprisingly, regardless of the position (ortho, meta, or
para), electronic nature, or steric bulk of the substituent on the
phenylsulfonyl azide, polymerization was successfully achieved
determined by MALLS because of their poor solubility in
THF and CHCl , they all had high molecular weights of over
3
10 kg/mol as determined by the relative calibration method.
We believe that the corresponding absolute molecular weights
would be much higher in view of the fact that for the other
polymers the M values obtained from MALLS were at least 2
3
2
n
and generally 3−5 times larger than those obtained from
standard calibration methods. In addition to aromatic sulfonyl
azides, alkylsulfonyl azides (e.g., 2j and 2k) also afforded high-
molecular-weight polymers (Table 2, entries 15 and 26). Thus,
diverse sulfonyl azides with different functionalities were
successfully introduced to the polyamidine structures. With
(
Table 2, entries 7−14). Although the absolute molecular
weights of several highly polar polymers could not be
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Journal of the American Chemical Society
Communication
AUTHOR INFORMATION
Corresponding Author
tlc@snu.ac.kr
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We dedicate this paper to Prof. Hie-Joon Kim on his retirement
and his outstanding contribution to education at SNU. We
thank NCIRF at SNU for supporting GC-MS experiments. We
are grateful for the financial support from the Basic Science
Research Program, the Nano-Material Technology Develop-
ment Program, and BRL through the National Research
Foundation of Korea.
Figure 1. THF SEC trace monitored using a UV detector at 254 nm.
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ASSOCIATED CONTENT
■
2
*
S
Supporting Information
Experimental details, synthesis, complete table of optimization
results, characterization data (TGA, DSC, SEC traces, etc.), and
spectra of the compounds. This material is available free of
charge via the Internet at http://pubs.acs.org.
(
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