Synthesis of a kinetically stabilized homoditopic nitrile N-oxide directed toward catalyst-free click polymerization

Article abstract of DOI:10.1246/cl.2010.420

A kinetically stabilized homoditopic nitrile N-oxide was prepared for a catalyst-free click polymerization that efficiently proceeded via 1,3-dipolar cycloaddition with several bifunctional alkyne, alkene, and nitrile monomers. The polymerization afforded the corresponding polymers with high molecular weights and yields.

Full text of DOI:10.1246/cl.2010.420

doi:10.1246/cl.2010.420
420
Published on the web April 5, 2010
Synthesis of a Kinetically Stabilized Homoditopic Nitrile N-Oxide Directed
toward Catalyst-free Click Polymerization
Young-Gi Lee, Morio Yonekawa, Yasuhito Koyama, and Toshikazu Takata*
Department of Organic and Polymeric Materials, Tokyo Institute of Technology, 2-12-1 O-okayama, Meguro-ku, Tokyo 152-8552
(Received January 8, 2010; CL-100026; E-mail: ttakata@polymer.titech.ac.jp)
O
N
C
O
N
C
A kinetically stabilized homoditopic nitrile N-oxide was
prepared for a catalyst-free click polymerization that efficiently
proceeded via 1,3-dipolar cycloaddition with several bifunc-
tional alkyne, alkene, and nitrile monomers. The polymerization
afforded the corresponding polymers with high molecular
weights and yields.
H3
C
C
CH3
MeO
O
O
OMe
H3
CH3
CHCl3, reflux, 12 h
96%
H3
C
C
CH3
O
N
O
N
3
+
O
O
MeO
OMe
H3
CH3
1-octyne
(2.5 equiv)
4
Scheme 2. Reaction of stable nitrile N-oxide 3 with 1-octyne.
Click chemistry1 based on the Cu(I)-catalyzed Huisgen
cycloaddition of azides with alkynes has generated particular
interests as a powerful synthetic tool for molecular integration.2
The reaction has been successfully used in polymer chemistry
for selective modification of versatile polymers to afford unique
architectures such as cyclic, block, dendritic, and network
polymers.3,4 However, the toxicity and explosiveness of azides,
in addition to the requirement of a Cu(I) catalyst, has led to
limitations in the use of this method.5 A promising substitute
1,3-dipole of azide would be nitrile N-oxide that has potential
utility to overcome these problems.6 [2 + 3]Cycloaddition of
nitrile N-oxide efficiently proceeds with not only alkynes but
also alkenes and nitriles to selectively produce the correspond-
ing nitrogen-containing heterocycles.7 Iwakura’s original work6a
prompted us to recently report a new click polymerization
exploiting homoditopic nitrile N-oxide generated in situ with
ditopic olefinic and acetylenic monomers through molecular
sieves-promoted polycycloaddition.8a,8c The polymerization fea-
tures mild reaction conditions, simple procedure, and broad
applicability based on the main chain heterocycles formed.8b To
avoid some limitations based on the use of precursor for unstable
ditopic nitrile N-oxide such as the requirement of molecular
sieves (4 ¡) and restricted temperature allowance, we have
undertaken the polycycloaddition using stable ditopic nitrile N-
oxide, considering Kanbara’s work.6d Herein, we disclose the
catalyst-free click polymerization exploiting a new kinetically
stabilized ditopic nitrile N-oxide9 as a 1,3-dipole with various
bifunctional dipolarophiles to emphasize the versatility and
productivity of the click reaction in polymer chemistry.
Table 1. Effects of solvent and reaction time on click polymer-
ization
R
O
O
N
O
O
O
N
N
O
O
R
O
N
C
C
+
Conditions
Solvent
OMe
MeO
5
3
OMe
MeO
n
H3
C
C
CH3
CH3
Poly-5
R =
H3
Temp Time
Mw
/Mn
Yield
/%
a
a
Entry Solvent
Mw
Mn
a
/°C
/h
1
2
3
4
5
6
DMF
CH2Cl2 reflux
CH2Cl2 reflux
CHCl3
CHCl3
CHCl3
80
12
2
12
1
2
12
3600
1600 2.2
94
80
93
60
84
95
19000 10300 1.9
20000 11000 1.9
18000
24000 10000 2.4
35000 16000 2.2
reflux
reflux
reflux
7000 2.6
aMn: number-average molecular weight and Mw: weight-average
molecular weight were estimated by size exclusion chromatog-
raphy (SEC, CHCl3, polystyrene standards).
polymerization, the model click reaction of 3 with 1-octyne
was carried out as shown in Scheme 2. The product 4 obtained
in a high yield as a single diastereomer certainly proved the
successful efficient polymerization. The regiochemistry of the
isoxazole moiety of 4 was confirmed by the NOESY correlations
observed between the isoxazole methyne proton and the methyl
protons of the spacer.10
Table 1 summarizes the results of the click polymerization
using 1,7-octadiyne (5), mainly to clarify the effects of solvent
and reaction time. The polymerization of 3 and 5 in DMF was
first investigated to result in the formation of polyisoxazole
Poly-5 with a relatively low molecular weight (Mw = 3600),
probably due to the hydrolysis of 3 to afford the corresponding
hydroxamic acid (Entry 1). Various experimental results of
Table 1 revealed that the click polymerization efficiently
proceeds in less-polar solvents such as CH2Cl2 and CHCl3.
In CH2Cl2, polymer molecular weight did not significantly
depend on reaction time (Table 1, Entries 2 and 3). On the other
hand, in CHCl3, the molecular weight of Poly-5 continuously
increased with the reaction time, to eventually give Poly-5
with Mw = 35000 in 95% yield (Entries 4-6). In both solvent
systems, only one regioisomer was preferentially formed as
Scheme 1 shows the synthetic route of kinetically stabilized
homoditopic nitrile N-oxide 3. We found that 3 could be easily
obtained in a high yield from a bisphenol A derivative as a bulky
spacer moiety, suggesting that various nitrile N-oxides can be
prepared by changing the diol spacer. Prior to the click
H3
HO
H3
C
CH3
OH
CH3
H3
C
CH3
CHO
CHO
CHO
K2CO3
MeO
F
+
MeO
O
O
OMe
DMF
140 °C
91%
C
H3
C
CH3
1
O
O
N
C
OH
OH
N
N
C
H3
C
CH3
H3
C
CH3
NCS
Et3N
NH2OH.HCl
NaOH
N
MeO
O
O
OMe
MeO
O
O
OMe
EtOH/H2O
99%
CHCl3
98%
H3C
CH3
H3C
CH3
2
3
1
Scheme 1. Synthetic route of stable ditopic nitrile N-oxide 3.
confirmed by H NMR.10
Chem. Lett. 2010, 39, 420-421
© 2010 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

421
Table 2. Synthesis of polyisoxazoles, polyisoxazolines, and
polyoxadiazole via polycycloadditiona
Table 3. Molecular weights and thermal properties of poly-
isoxazoles, polyisoxazolines, and polyoxadiazole
a
a
a
Mw/Mn Tg/°Cc Td5/°Cd
Products
Entry
Dipolarophile
Yield/%
Entry Products
Mw
Mn
O
O
R
O
O
N
N
1
2
3
4
Poly-5
Poly-6
Poly-7
Poly-8
Poly-9
35000 16000
33000 20000
2.2
1.6
3.3
1.7
2.2b
1.9
1.7
1.4
170
165
¹41
152
259
151
114
146
365
341
324
338
357
312
335
336
O
O
1
O
O
93
OMe
MeO
O
6
Poly-6
n
23000
7000
O
N
O
R
O
N
54000 31000
21000b 9400b
O
O
O
m
O
2
92
98
91
O
5
m
7
OMe
MeO
n
(Mn: 1300)b
Poly-7
6
7e
8e
Poly-10 21000 11000
Poly-11 19000 11000
Poly-12
N
O
O
R
O
N
3
7000
5100
OMe
MeO
Poly-8
8
n
aEstimated by SEC (CHCl3, bDMF, polystyrene standards).
cGlass transition temperature (Tg) was obtained at a heating rate
of 10 °C min¹1 under N2 (flow rate 50 mL min¹1). d5% Thermal
weight loss temperatures (Td5) were obtained at a heating rate of
10 °C min
O
O
O
O
O
O
N
N
N
N
R
O
O
N
N
4
O
O
O
O
OMe
MeO
Poly-9
9
n
¹1
under N2 (flow rate 50 mL min¹1). eReaction
O
O
R
O
O
N
N
O
O
O
O
O
O
O
O
O
condition: chlorobenzene, reflux, 12 h.
5
99
O
O
O
O
O
O
OMe
OMe
MeO
10
n
Poly-10
the present click polymerization will provide a new entry to the
syntheses of various polymers including functionalized polymers.
O
O
O
R
O
N
N
6c
O
O
99
91
O
O
O
11
MeO
O
Poly-11
n
O
N
This work was financially supported by the Global COE
program (Tokyo Institute of Technology), Mizuho Foundation
for the Promotion of Science, and the Sasagawa Fellowship from
the Nippon-Foundation to Y.G.L.
O
O
R
N
N
N
C
7c
C
N
N
12
OMe
MeO
Poly-12
n
aReaction condition: CHCl3, reflux, 12 h. bDetermined by
integral ratio of 1H NMR spectrum. cReaction condition:
chlorobenzene, reflux, 12 h.
References and Notes
1
a) H. C. Kolb, M. G. Finn, K. B. Sharpless, Angew. Chem., Int. Ed.
2001, 40, 2004. b) C. W. Tornøe, C. Christensen, M. Meldal, J. Org.
Chem. 2002, 67, 3057.
For a selected review, see: C. J. Hawker, K. L. Wooley, Science
2005, 309, 1200.
Various bifunctional acetylenes, olefins, and nitrile mono-
mers could be employed as monomers (Tables 2 and 3). The
polymerization of diyne monomers such as 6 and acetylene-
terminated polytetrahydrofuran 7 proceeded well to afford the
corresponding polyisoxazoles with high molecular weights
(Table 3, Entries 2 and 3). We found that diene monomers such
as 1,7-octadiene (8), N,N¤-1,3-phenylenedimaleimide (9), and
bisacrylate 10 were also reactive enough to afford polyisoxazo-
lines with high molecular weights in high yields. Synthesis of
polyisoxazoline Poly-11 with a similar molecular weight to
Poly-10 required high temperature due to the lower reactivity
resulting from the steric hindrance of the methacrylate moiety of
11 (Table 3, Entries 6 and 7).
2
3
For selected reports of click polymerization exploiting Huisgen
reaction, see: a) D. J. V. C. van Steenis, O. R. P. David, G. P. F.
van Strijdonck, J. H. van Maarseveen, J. N. H. Reek, Chem.
Commun. 2005, 4333. b) J.-F. Lutz, Angew. Chem., Int. Ed. 2007, 46,
1018. c) D. Fournier, R. Hoogenboom, U. S. Schubert, Chem. Soc.
Rev. 2007, 1369. d) J. Nicolas, G. Mantovani, D. M. Haddleton,
Macromol. Rapid Commun. 2007, 28, 1083.
a) R. K. O’Reilly, M. J. Joralemon, C. J. Hawker, K. L. Wooley,
Chem.®Eur. J. 2006, 12, 6776. b) O. Altintas, B. Yankul, G. Hizal,
U. Tunca, J. Polym. Sci., Part A: Polym. Chem. 2006, 44, 6458. c)
D. D. Díaz, K. Rajagopal, E. Strable, J. Schneider, M. G. Finn,
J. Am. Chem. Soc. 2006, 128, 6056. d) S. R. Gondi, A. P. Vogt, B. S.
Sumerlin, Macromolecules 2007, 40, 474.
4
It was noticed that nitrile groups were also active to this
click reaction and the polymerization of adiponitrile (12)
actually proceeded well to give polyoxadiazole Poly-12,
although it showed low molecular weight, probably owing to
the low reactivity.10
The thermal properties of the obtained polymers were
studied using DSC and TGA (Table 3). The glass transition
temperature (Tg) appeared in the range from ¹41 to 259 °C,
depending on the structure of dipolarophile monomers. The
thermal weight loss temperature (Td5) was in the range from 312
to 365 °C, indicating the thermal stability of the isoxazoles,
isoxazolines, and oxadiazole skeletons.
In summary, this paper has demonstrated a new click poly-
merization utilizing a kinetically stabilized nitrile N-oxide 3
in the absence of additive. The advantageous features of the
present click polymerization include good monomer versatility
(bifunctional alkene, alkyne, and nitrile), stable C-C bond forma-
tion, catalyst-free reaction, and a non-explosive 1,3-dipole. Thus,
5
6
K. E. Russell, J. Am. Chem. Soc. 1955, 77, 3487.
a) Y. Iwakura, S. Shiraishi, M. Akiyama, M. Yuyama, Bull. Chem.
Soc. Jpn. 1968, 41, 1648. b) Y. Iwakura, K. Uno, S.-J. Hong, T.
Hongu, Polym. J. 1971, 2, 36. c) S. J. Hong, Y. Iwakura, K. Uno,
Polymer 1971, 12, 521. d) T. Kanbara, T. Ishii, K. Hasegawa, T.
Yamamoto, Polym. Bull. 1996, 36, 673. e) S. Grecian, V. V. Fokin,
Angew. Chem. 2008, 120, 8409. f) I. Singh, Z. Zarafshani, J.-F. Lutz,
F. Heaney, Macromolecules 2009, 42, 5411.
For selected review on isoxazoles, see: S. A. Lang, Y. I. Lin, in
Comprehensive Heterocyclic Chemistry, ed. by A. R. Katritzky,
C. W. Rees, Pergamon, Oxford, 2000, Vol. 6, p. 1.
For a related our report of the click polymerization exploiting homo-
ditopic nitrile oxides, see: a) Y. Koyama, M. Yonekawa, T. Takata,
Chem. Lett. 2008, 37, 918. b) Y. G. Lee, Y. Koyama, M. Yonekawa,
T. Takata, Macromolecules 2009, 42, 7709. c) Y. G. Lee, Y. Koyama,
M. Yonekawa, T. Takata, Macromolecules 2009, submitted.
For selected reports of stable nitirile N-oxides, see: a) P. Beltrame, C.
Veglio, M. Simonetta, J. Chem. Soc. B 1967, 867. b) C. Grundmann,
R. Richter, J. Org. Chem. 1968, 33, 476.
7
8
9
10 Supporting Information is available electronically on the CSJ-
Journal Web site, http://www.csj.jp/journals/chem-lett/index.html.
Chem. Lett. 2010, 39, 420-421
© 2010 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/