Cascade functionalization of unsaturated bond-containing polymers using ambident agents possessing both nitrile N-oxide and electrophilic functions

Article abstract of DOI:10.1039/c2cc35158g

We developed a powerful and highly reliable cascade functionalization technique for constructing sophisticated macromolecular architectures. Central to the technique are the ambident agents having combined functions of a nitrile N-oxide group and an electrophile. The agents proved capable of facile catalyst- and solvent-free functionalization of polymers and further integrations involving cross-linking.

Full text of DOI:10.1039/c2cc35158g

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Cascade Functionalization of Unsaturated Bond-Containing Polymers
Using Ambident Agents Possessing both Nitrile N-Oxide and
View Online
Electrophilic Functions
Yasuhito Koyama,*a Kaori Miura,a Sumitra Cheawchan,a Akishige Seo,a and Toshikazu Takata*a
5
Received (in XXX, XXX) Xth XXXXXXXXX 200X, Accepted Xth XXXXXXXXX 200X
First published on the web Xth XXXXXXXXX 200X
DOI: 10.1039/b000000x
We envisioned that, if various unsaturated bonds, including
internal olefin and CN groups with relatively low reactivity,
45 are available, functionalization should enable modification
and cross-linking of many unsaturated bond-containing
polymers such as natural rubber, synthetic rubbers, and CN-
containing polymers. It should also provide new pathways to
development of chemical products made from polymers such
50 as micelle, fiber, sheet, and film that serve as reactive
scaffolds for molecular integration.
We developed
a powerful and highly reliable cascade
functionalization technique for constructing sophisticated
10 macromolecular architectures. Central to the technique are the
ambident agents having combined functions of a nitrile N-oxide
group and an electrophile. The agents proved capable of facile
catalyst- and solvent-free functionalization of polymers and
further integrations involving cross-linking.
15
Cascade functionalization1 of macromolecules based on the
Cu-catalyzed Huisgen cycloaddition2 of azides to alkynes has
generated particular interests as a powerful method for molecular
integration of polymers. The method has been widely adopted
for the constructiokn of highly sophisticated macromolecular
20 architectures such as graft polymers, bioconjugated polymers,
functional surface, and cross-linked polymers, due to the simple
procedure and the high reaction efficiency.3 However, the
explosiveness of azides and the requirement of a Cu catalyst have
limited its use.4 In addition, the method also limits the polymer
25 versatility because it requires the introduction of alkyne or azide
functionality into the trunk polymer in advance.
Herein, we introduce
a new cascade functionalization
technique involving use of an ambident agent (Fig. 1). We
describe the model functionalization reaction of the agent, with
55 both nitrile N-oxide5 and electrophilic functions, and investigate
the application of the technique to polymer modification.
Building on our previous work,6 we synthesized epoxide- and
ester-containing ambident agents (1 and 2, Scheme 1)7 and the
structures of 1 and 2 were determined by 1H NMR, 13C NMR, IR,
60 and FAB HRMS measurements.7
Intrigued by these techniques but mindful of their
limitations, we undertook the development of a more versatile,
powerful, and byproduct-free functionalization method,
30 optimally one that could enable large-scale macromolecular
synthesis.
Scheme 1 Structures of ambident agents (1 and 2) and the model ligation
reaction of 1 with isobutyronitrile and various nucleophiles. Reagents and
Conditions: a) Et2NH (1.05 equiv), CHCl3, 50 °C, 2 d; b) PhOH (1.05
65 equiv), K2CO3 (1.3 equiv), DMF, 120 °C, 12 h; c) BuSH (1.05 equiv)
K2CO3 (1.3 equiv), DMF, 120 °C, 12 h; d) PhCOOH (1.05 equiv), TBAB
(3 mol%), CH3CN, reflux, 1 d.
Fig. 1 Schematic representation of a new cascade functionalization using
an ambident agent having nitrile N-oxide and electrophilic functions.
35 a Department of Organic and Polymeric Materials, Tokyo Institute of
Technology, 2-12-1 (H-126), Ookayama, Meguro, Tokyo 152-8552,
Japan; E-mail: ykoyama@polymer.titech.ac.jp,
Before investigating the use of 1 as a general tool for
70 implementing polymer reactions, we performed a model reaction
of 1 with isobutyronitrile and various nucleophiles as shown in
Scheme 1. Treatment of 1 with isobutyronitrile in DMF at 90 °C
without any catalyst afforded oxadiazole 3 as a single isomer in
quantitative yield. The regiochemistry of the oxadiazole moiety
75 of 3 was confirmed by the characteristic signals of the 1,2,4-
ttakata@polymer.titech.ac.jp
† Electronic Supplementary Information (ESI) available: [Synthesis of
40 ambident agents (1 and 2), typical cascade functionalization of polymers,
IR, 1H NMR, 13C NMR, and FAB-HR-MS spectra data.]. See
DOI: 10.1039/b000000x/
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 1

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Page 2 of 4
oxadiazole in the 13C NMR spectrum.7 Subsequent catalyst-free
nucleophilic attack at the terminal epoxy moiety of 3 was 55 afforded the nitrile N-oxide adduct in 26% conversion yield
examined using various nucleophiles. Treatment with (entry 1). In addition, prolonged reaction time to 2 h increased the
surprise, press-grinding NR with powdery 2 at 70 °C for 1 h
a
View Online
nucleophile Et2NH in particular gave the corresponding adduct 4a
in 99% yield without any catalyst. Similarly, nucleophiles such
as phenol and thiol gave 4b and 4c in quantitative yields in the
conversion yield to 42% (entry 2), clearly suggesting the
remarkable acceleration of the cycloaddition reaction. Similarly,
polymer reactions of two commercially available elastomers,
5
presence of K2CO3, whereas the treatment with benzoic acid 60 acrylonitrile–butadiene rubber (NBR) and ethylene–propylene–
afforded 4d in the presence of TBAB8 in 84% yield. These results
strongly indicate the usefulness of as cascade
diene terpolymer (EPDM), gave the corresponding polymers in
high conversion yields (entries 3 and 4).
1
a
10 functionalization tool for integrating various functionalities on
the unsaturated bond-containing materials.
To clarify the time-dependent conversion of 1, we performed
the polymer reactions using polyacrylonitrile (PAN), as
summarized in Table 1. The reaction in DMF using 1.0 equiv of
15 1 per repeating unit of PAN resulted in the formation of
polyoxadiazole (Scheme 2 and Table 1). The reaction proceeded
efficiently with the increase in reaction time but achieved only up
to ca. 50% conversion, probably for two reasons: (i) the reaction
rate obeys inherently the second-order kinetics depending on both
20 concentrations of the remaining CN moieties on the main chain
and 1, and (ii) steric repulsion around the main chain increases
with increase in conversion of the resulting polymer (entries 1–4).
The reaction of ester-containing ambident agent 2, which is
bulkier than 1, was carried out for comparison to actually afford
25 the corresponding polymer in a moderate conversion yield (37%,
entry 5).
65
70
Scheme 3 Functionalization of NR with 1 and 2.
Table 2 Functionalization of NR using ambident agents 1 and 2.
entry
reagent
time (h)
yield (%)a
conversion (%)b
1
2
3
4
5c
6
1
1
1
1
1
2
1
2
99
99
3
8
24
96
72
98
43
49
>99
30
99
>99
99
24
MeOH-insoluble part. Estimated by 1H NMR. The reaction was
a
b
c
75 carried out with 1 (1.0 equiv). After 24 h and 48 h, the additional portions
of 1 (1.0 equiv) were added to the mixture.
30
Table 3 Functionalization of various polymers with 2 under solvent-free
conditions.
entry
polymer
NR
time (h) yield (%)a conversion (%)b
1
2
3
4
1
2
1
1
99
96
76
92
26
Scheme 2 Functionalization of PAN with 1 and 2.
NR
42
olefin: >99, CN: 71
35
NBR
EPDM
35 Table 1 Functionalization of PAN using ambident agents 1 and 2.
entry
reagent
time (h)
yield (%)a
conversion (%)b
a MeOH-insoluble part. b Estimated by 1H NMR.
1
2
3
4
5
1
1
1
1
2
1
4
99
98
99
98
74
18
32
50
53
37
80
To demonstrate the versatility of such ambident agents, we
prepared an internal alkyne-containing polyurethane and
performed the polymer reaction with 2. As a result, the
cycloaddition reaction using 1.0 equivalent of 2 underwent
smoothly to afford the corresponding isoxazole-containing
24
96
24
a MeOH-insoluble part. b Estimated by 1H NMR.
85 polymer in a quantitative conversion yield (Scheme 4), strongly
suggesting both the chemoselectivity of 2 independent on the
presence of acidic urethane N-H and the high reactivity of 2 with
internal alkynes.6i
Next, we performed the polymer reaction using natural rubber
(NR) as a representative internal-olefin-containing polymer, as
shown in Scheme 3. Cycloaddition reaction using 1.0 equiv of 1
40 per the repeating unit of NR proceeded efficiently to afford the
corresponding functionalized NR with
a
time-dependent
90
conversion ratio of up to ca. 50% (Table 2, entries 1–4). By the
considerable effort, we noticed that nitrile N-oxide 1 gradually
isomerized to the isocyanate at high temperature under the
45 reaction conditions,9 and twice additions of a portion of 1 (1.0
equiv) after 24 h and 48 h led to quantitative conversion yield
(entry 5). For comparison, reaction with 2 afforded ester-
containing NR in 30% conversion yield (entry 6).
95
These results prompted us to theorize that solvent-free reaction
50 not only enables rapid conversion but should also be ideal for
large-scale macromolecular synthesis. To prove this idea, we
performed the polymer reaction without any solvent, press-
grinding the reactants in a mortar (Table 3). To our pleasant
100
Scheme 4 Functionalization of internal alkyne-containing polymer with 2.
2 | Journal Name, [year], [vol], 00–00
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With these electrophile-containing elastomers in hand, we 35 decreases with increasing feed ratio of the diamine spacer. This
demonstrated the cross-linking reaction using
a
ditopic
result is in a good agreement with the observed swelling behavior.
In conclusion, we have designed and constructed a facile and
widely applicable cascade functionalization technique for use
nucleophile. To evaluate mechanical properties, we performed the
cross-linking reaction using a CHCl3 solution of NR possessing
just 2% epoxy functionality with various amounts of N,N-
View Online
5
between polymers with unsaturated bonds such as C≡N, internal
diethylhexanediamine in a Teflon vessel. Reaction at 40 °C for 24 40 C=C, and C≡C bonds and various nucleophiles via catalyst- and
h gave cross-linked NR as a translucent sheet (Scheme 5). The
density of the network chain, the cross-linking ratio of the
resulting polymers, and the conversion yield of the diamine were
solvent-free 1,3-dipolar cycloadditions and subsequent
byproduct-free nucleophilic reaction. The new ambident agents
central to this technique show promise as a means for creating
versatile polymer materials in such domains as shape-retaining
45 surface modification of cross-linked polymers, adhesion between
incompatible soft interfaces or between organic and inorganic
interfaces, and novel molecular integrations using highly
processed plastics made from ubiquitous polymers as the scaffold.
This work was financially supported by a Grant-in-Aid for
50 Scientific Research from the Ministry of Education, Culture,
Sports, Science and Technology, Japan (No. 24685023) and
the Japan Securities Scholarship Foundation.
10 estimated using a modified Flory–Rehner equation10 based on the
swelling ratio of the polymer in toluene (Table 4).
Notes and references
1 For selected reviews, see; (a) C. J. Hawker and K. L. Wooley, Science,
55
60
65
70
75
80
85
90
95
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W. H. Binder, R. Sachsenhofer, Macromol. Rapid Commun., 2008, 29,
952; (j) J. A. Johnson, M. G. Finn, J. T. Koberstein, N. J. Turro,
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Wooley, A. M. Nyström, D. J. Burke, M. J. Kade, C. J. Hawker, Chem.
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Scheme 5 Cross-linking of NR.
15 Table 4 Effect of diamine feed ratio on the properties of cross-linked NR.
entry
cross- swelling ratio degree of cross- yield (%)
Td5 (°C)
linker (%)
(%)a
–
link (%)b
–
ref.
1
–
5
–
345
338
340
340
930
540
380
0.41
1.2
87
98
99
2
25
50
3
2.5
2 H. C. Kolb, M. G. Finn and K. B. Sharpless, K. B. Angew. Chem., Int.
Ed., 2001, 40, 2004.
entry Tg (°C) tensile strength elongation (%)d
Young’s
Modulus
(MPa)e
0.62
(MPa)c
3 For selected reports, see: (a) M. Malkoch, R. J. Thibault, E.
Drockenmuller, M. Messerschmidt, B. Voit, T. P. Russell, C. J.
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4 K. E. Russell, J. Am. Chem. Soc., 1995, 77, 3487.
ref.
1
–65
–57
–57
–56
6.34
1100
f
f
f
–
–
–
2
5.04
5.20
698
452
0.50
0.86
3
a
b
Swelled by soaking in toluene overnight. Estimated by modified
Flory–Rehner equation. c Value of the stress maxima. d Value of the strain
maxima. Estimated from the slope in the range from 0 to 100% strain.
5 For selected reports of stable nitrile N-oxides, see: (a) P. Beltrame, C.
Veglio and M. Simonetta, J. Chem. Soc. B., 1967, 867; (b) C.
Grundmann and R. Richter, J. Org. Chem., 1968, 33, 476.
e
f
Not estimated.
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20 Two findings obtained have clearly suggested the high efficiency
of the epoxy functionality in the polymer: (i) the cross-linking
ratio increases with increase in feed ratio of the diamine and (ii)
the cross-linking reaction efficiency is sufficiently high. Thermal
properties such as decomposition temperature (Td5) and glass
25 transition temperature (Tg), evaluated by differential scanning
calorimetry (DSC) and thermogravimetry (TGA), reveal that all
cross-linked polymers appeared at the same temperature region,
probably because the ingredients in the polymers were essentially
identical except for the amount of diamine spacer. Stress–strain
30 curves for the network polymers are consistent with the feed ratio
of the diamine cross-linker.
100 7 See, supporting information.
8 A. Khalafi-Nezhad, M. N. Soltani Rad and A. Khoshnood, Synthesis,
2003, 2552.
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From measurements of ultimate tensile strength and elongation,
we calculated Young’s modulus on the basis of Hooke’s law.7
For the cross-linked NRs, stress clearly increases and strain
105
162.
10 D. S. Campbell, J. Appl. Polym. Sci., 1970, 14, 1409.
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 3

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Page 4 of 4
Graphical Abstract
Cascade Functionalization of Unsaturated Bond-Containing Polymers Using Ambident Agents Possessing both Nitrile N-Oxide
View Online
and Electrophilic Functions
5
A new cascade functionalization technique of unsaturated bond-containing polymers was developed by using ambident
agents having nitrile N-oxide and electrophiles.
4 | Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]