Cyclic alkoxyamine-initiator tethered by azide/alkyne-"click"- Chemistry enabling ring-Expansion vinyl polymerization providing macrocyclic polymers

Article abstract of DOI:10.1002/pola.24126

A cyclic initiator for the nitroxide-mediated controlled radical polymerization (NMP) is a powerful tool for the preparation of macrocyclic polymers via a ring-expansion vinyl polymerization mechanism. For this purpose, we prepared a Hawker-type NMP-initiator that includes an azide and a terminal alkyne as an acyclic precursor, which is subsequently tethered via an intramolecular azide/alkyne-"click"-reaction, producing the final cyclic NMP-initiator. The polymerization reactions of styrene with cyclic initiator were demonstrated and the resultant polymers were characterized by the gel permeation chromatography (GPC) and the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). These results prove that the ring-expansion polymerization of styrene occurred together with the radical ring-cross-over reactions originating from the exchange of the inherent nitroxides generating macrocyclic polystyrenes with higher expanded rings. 2010 Wiley Periodicals, Inc.

Full text of DOI:10.1002/pola.24126

Cyclic Alkoxyamine-Initiator Tethered by Azide/Alkyne-‘‘Click’’-Chemistry
Enabling Ring-Expansion Vinyl Polymerization Providing
Macrocyclic Polymers
ATSUSHI NARUMI,* SYLVIA ZEIDLER, HAITHAM BARQAWI, CLAUDIA ENDERS, WOLFGANG H. BINDER
Department of Natural Sciences II (Chemistry and Physics), Martin-Luther University Halle-Wittenberg,
Institute of Chemistry/Chair of Macromolecular Chemistry, Von-Danckelmann-Platz 4; D-06120 Halle (Saale), Germany
Received 2 April 2010; accepted 10 May 2010
DOI: 10.1002/pola.24126
Published online in Wiley InterScience (www.interscience.wiley.com).
ABSTRACT: A cyclic initiator for the nitroxide-mediated con-
trolled radical polymerization (NMP) is a powerful tool for the
preparation of macrocyclic polymers via a ring-expansion vinyl
polymerization mechanism. For this purpose, we prepared a
Hawker-type NMP-initiator that includes an azide and a termi-
nal alkyne as an acyclic precursor, which is subsequently
tethered via an intramolecular azide/alkyne-‘‘click’’-reaction,
producing the final cyclic NMP-initiator. The polymerization
reactions of styrene with cyclic initiator were demonstrated
and the resultant polymers were characterized by the gel per-
meation chromatography (GPC) and the matrix-assisted laser
desorption/ionization time-of-flight mass spectrometry (MALDI-
TOF MS). These results prove that the ring-expansion polymer-
ization of styrene occurred together with the radical ring-cross-
over reactions originating from the exchange of the inherent
nitroxides generating macrocyclic polystyrenes with higher
C
V
expanded rings. 2010 Wiley Periodicals, Inc. J Polym Sci Part A:
Polym Chem 48: 3402–3416, 2010
KEYWORDS: azide/alkyne-‘‘click’’-reaction; macrocyclics; MALDI;
radical crossover reaction; radical polymerization; ring-
polymer
INTRODUCTION Macrocyclic polymers represent interesting
research targets for both theoretical and synthetic chemists
because of their characteristic properties, which strongly dif-
fer from those of their linear counterparts.1–6 To cite some
representative recent examples, Schappacher and Deffieux
reported that macrocyclic copolymer brushes prepared via liv-
ing ionic polymerization methods show self-assembly to form
supramolecular nano-tubes.7,8 Another example relates to the
different chain dynamics of cyclic versus linear polymers due
to the absence of dangling chain ends.1,4 In all cases, a signifi-
cant synthetic effort needs to be undertaken to achieve macro-
cyclic polymers free of contaminant linear polymers. A com-
mon strategy to construct the macrocyclic polymers requires
the process of an end-to-end cyclization using chemical reac-
tions with high reactivities, such as coupling reactions of a,x-
polymer dianions,9,10 addition reactions based on HX/Lewis
acid initiating systems,11 transketalizations,12,13 azide/alkyne-
click-reactions,14–18 or ring-closing olefin metathesis.18–21
tiators25–28 have been successfully used to this purpose. Fur-
thermore, N-heterocyclic carbenes were reported to mediate
the ring-expansion polymerizations of lactide and e-caprolac-
tone to generate cyclic polyesters.29–31 Only few studies have
been reported on the ring-expansion polymerization applicable
to conventional vinyl monomers, except Pan and coworkers32
who reported that the 60Co c-ray-induced polymerization of
methyl acrylate in the presence of cyclic initiator containing
two dithioester linkages producing cyclic vinylpolymers. The
ring-expansion vinyl polymerization should become a promis-
ing method that easily leads to macrocyclic polymer brushes
when combined with the polymerizations of macromomomers.
In this work, we report a new synthetic route potentially pro-
viding macrocyclic polymers in which the propagation of a vinyl
monomer proceeds under a ring-expansion mechanism relying
on a controlled radical polymerization process. The strategy is
based on the featured mechanism of the nitroxide-mediated
controlled radical polymerization (NMP),33,34 where a propaga-
tion occurs by addition of a vinyl monomer to the polymeriza-
tion-active radical that is derived from the homolysis and
recombination of a CAON bond of an alkoxyamine by heating.
Thus, a cyclic alkoxyamine derivative in which the head and tail
are covalently linked can be used to initiate the formation of
cyclic vinyl polymers via the ring-expansion polymerization
mechanism as shown in Chart 1. It should be noted that
Another approach uses cyclic initiators to induce a ring-
expansion polymerization and thus does not rely on the use of
end-to-end cyclizations. Strategies based on the polyhomologa-
tion reaction of boracyclanes using an ylide dimethylsulfoxo-
nium methylide as the monomer,22 ring-opening metathesis
polymerizations of cyclooctene via cyclic Ru-initiators,23,24 or
ring-opening polymerization of e-caprolactone via cyclic tin-ini-
*Present address: Department of Polymer Science and Engineering, Graduate School of Science and Engineering, Yamagata University, Jonan 4-3-
16, Yonezawa 992-8510, Japan.
Correspondence to: W. H. Binder (E-mail: wolfgang.binder@chemie.uni-halle.de) or A. Narumi (E-mail: narumi@yz.yamagata-u.ac.jp)
C
V
Journal of Polymer Science: Part A: Polymer Chemistry, Vol. 48, 3402–3416 (2010) 2010 Wiley Periodicals, Inc.
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ARTICLE
1H-1,2,3-triazol-4-yl)methyl]amine (TBTA)43 were prepared
according to literature procedures.
Instruments
1H- (400 MHz) and 13C-NMR (100 MHz) spectra were
recorded on a Varian Gemini 2000 instrument. The 1H-
(500 MHz) and 13C-NMR (125 MHz) spectra were recorded
on a Varian Unity Inova 500 instrument. CDCl3 (Isotec, 99.8
atom% D) and 1,1,1,3,3,3-hexafluoro-2-propanol-d2 (Isotec,
99 atom% D) were used as solvents. IR spectra were
recorded on a Bruker Vertex 70 FT-IR spectrometer. Electro-
spray ionization time-of-flight mass spectrometer (ESI-TOF
MS) analysis was performed using a Bruker Daltonics Focus
microTOF II. Matrix-assisted laser desorption/ionization
time-of-flight mass spectrometer (MALDI-TOF MS) and gel
permeation chromatography (GPC) are described later.
CHART 1 Concept of the ring-expansion polymerization initi-
ated by a cyclic alkoxyamine derivative producing macrocyclic
vinyl polymers.
alkoxyamine-containing ring-compounds can be further
expanded via radical ring-crossover reactions as reported by
Otsuka and coworkers,35 who have focused on the polymer syn-
thesis utilizing ‘‘dynamic covalent bonds.’’ We first describe here
that an acyclic 4-(1-(tert-butyl-(2-methyl-1-(30-ethynylphenyl-
propyl)aminooxy)ethyl)benzyl 4-azidobenzoate (acyclic precur-
sor 1, Scheme 1), in which the alkoxyamine-backbone is based
on the Hawker-type initiator,36 was prepared as a starting point
for the cyclic NMP-initiator. Strategically, the azide/alkyne-
‘‘click’’-reaction37–42 of 1 was projected under high dilution con-
ditions to produce cyclic NMP-initiator 2 as illustrated in
Scheme 1. The resulting cyclic NMP-initiator 2 was then pro-
jected to serve as initiator for the NMP of styrene aiming at the
generation of cyclic polystyrenes.
2,2,5-Trimethyl-4-(30-(trimethylsilyl)ethynyl)
phenyl-3-azahexane-3-nitroxide (4)
A few drops of dibromoethane were added to magnesium
(850 mg, 35.0 mmol) in dry THF (3.00 mL) and the mixture
was vigorously stirred. After 10 min, a solution of (2-(30-bro-
mophenyl)ethynyl)trimethylsilane (5.00 g, 19.7 mmol) in dry
THF (20 mL) was added dropwise over 1 h with vigorously
stirring and then the mixture was refluxed for 30 min. After
cooling to room temperature, the mixture was added to
N-tert-butyl-a-isopropylnitrone (2.82 g, 19.7 mmol) with a
syringe and the resulting solution was refluxed for 3 h. After
cooling to room temperature, saturated ammonium chloride
solution (5.00 mL) was added, the formed solids were dis-
solved by water (15 mL), chloroform (20 mL) was added,
and the organic layer was separated. The aqueous layer was
extracted with chloroform (20 mL ꢁ 3) and the combined
organic layers were dried over sodium sulfate and then
evaporated to dryness. The residue was redissolved in meth-
anol (100 mL) and 25% ammonium hydroxide solution
(4.00 mL) and a catalytic amount of copper(II) acetate
hydrate were added. A stream of air was bubbled until the
color of the mixture changed from a yellow into a dark
brown (2 h). The mixture was evaporated and the residue
was dissolved in a mixture of chloroform (50 mL) and 10%
KHSO4 solution (10 mL). The organic layer was separated
and the aqueous layer was extracted with chloroform (20 mL
ꢁ 3). The combined organic layers were washed with satu-
rated sodium bicarbonate solution (20 mL), dried over
sodium sulfate, and evaporated to dryness. The residue was
purified by column chromatography on silica gel, eluting
with 50: 1 hexane/ethyl acetate gradually increasing to 20: 1
to yield 4 (3.19 g, 51.2%) as a viscous orange oil. Data for 4:
Rf ¼ 0.36 (hexane/ethyl acetate, 20: 1); 1H NMR (400 MHz,
CDCl3, in the presence of pentafluorophenyl hydrazine): d
7.24 (s, 1H, phenyl-H), 7.13 (d, 1H, 3J ¼ 7.5 Hz, phenyl-H),
7.08 (d, 1H, 3J ¼ 7.5 Hz, phenyl-H), 6.95 (m, 1H, phenyl-H),
3.11 (d, 1H, 3J ¼ 9.4 Hz, NCH), 2.01 (m, 1H, CH), 1.06 and
EXPERIMENTAL
Materials
Tetrahydrofuran (THF) was refluxed over sodium and benzo-
phenone and distilled prior to use. Dichloromethane and N,N-
dimethylformamide [DMF, Fluka (Buchs, Switzerland) >99.8%]
were refluxed with calcium hydride and distilled prior to use.
p-Vinylbenzylchloride [Aldrich (Milwaukee, WI), 90%] was used
after passing through aluminum oxide [Aldrich (Milwaukee,
WI), activated, neutral, Brockmann I, STD grade, approx. 150
mesh, 58 Å] using toluene as an eluent. Styrene [Aldrich (Mil-
waukee, WI), 99.8%] was extracted with aqueous sodium-hy-
droxide solution, dried and distilled before use. (2-(30-Bromo-
phenyl)ethynyl)trimethylsilane (97%), dibromoethane (99%),
magnesium (chips, 4 þ 30 mesh, 99.98%), copper(II) acetate
hydrate (98%), (R,R)-(ꢀ)-N,N0-bis(3,5-di-tert-butylsalicyli-
dene)-1,2-cyclohexanediaminomanganese(III) chloride, so-
dium borohydride (99%), 4-aminobenzoic acid (99%), sodium
nitrate (>99.0%), sodium azide (99.5%), cesium carbonate
(Cs2CO3, 99%), hexamethylphosphoric acid triamide (HMPA,
99%), tetrabutylammonium fluoride (TBAF, 1.0 M solution in
THF), tetrakis(acetonitrile)copper(I) hexafluorophosphate
([(CH3CN)4Cu]PF6), and N-ethyldiisopropylamine (DIPEA,
99%), were purchased from Aldrich (Milwaukee, WI) and used
as received. Ammonium chloride (>99%), ammonium hydrox-
ide solution (25%), and di-tert-butylperoxide (>95%) were
purchased from Fluka (Buchs, Switzerland) and used as
received. N-tert-Butyl-a-isopropylnitrone36 and tris[(1-benzyl-
3
0.68 (s, 9H, NCCH3), 0.86 and 0.63 (d, 6H, J ¼ 6.5 Hz, CH3),
3
0.31 and 0.06 (d, 6H J ¼ 6.5 Hz, CH3), -0.01 (s, 9H, SiCH3);
13C NMR (100 MHz, CDCl3, in the presence of pentafluoro-
phenyl hydrazine): d 134.11 (phenyl-C), 133.39 (phenyl-CH),
132.36 (phenyl-CH), 130.57 (phenyl-CH), 130.45 (phenyl-
CYCLIC ALKOXYAMINE ENABLING RING-EXPANSION VINYL POLYMERIZATION, NARUMI ET AL.
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JOURNAL OF POLYMER SCIENCE: PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
SCHEME 1 Procedures for the gen-
eration of cyclic alkoxyamines and
their use as the initiator for the
polymerization: i) the ‘‘click’’ reac-
tion of acyclic precursor 1 using
tetrakis(acetonitrile)copper(I) hexa-
fluorophosphate ([(CH3CN)4Cu]PF6),
N-ethyldiisopropylamine (DIPEA),
and tris[(1-benzyl-1H-1,2,3-triazol-4-
yl)methyl]amine (TBTA) in N,N-
dimethylformamide (DMF) at room
temperature to produce cyclic initia-
tors 2 and ii) polymerization of sty-
rene (St) with
2 in 1,1,1,3,3,3-
hexafluoro-2-phenyl-2-propanol
(HFPP) to produce macrocyclic
polystyrenes 3.
CH), 129.50 (phenyl-CH), 127.82 (phenyl-CH), 127.64 (phenyl-
CH), 123.15 (phenyl-C), 122.46 (phenyl-C), 105.62 (phenyl-
C:), 103.90 (phenyl-C:), 95.55 (:C-Si), 93.39 (:C-Si),
73.65 (NC), 71.05 (NCH), 31.44 (CH), 31.24 (CH), 30.31 (CH3)
26.88 (CH3), 21.49 (CH3), 20.48 (CH3), 18.52 (CH3), 18.46
(CH3), -0.01 (SiCH3), -0.15 (SiCH3); IR (cmꢀ1): m 3423, 2961,
2871, 2156, 1598, 1577, 1478, 1426, 1384, 1362, 1249, 1215,
920, 841, 760, 699, 631; ESI-TOF MS exact mass calcd. for
dene)-1,2-cyclohexanediaminomanganese(III) chloride (680 mg,
1.07 mmol), and di-tert-butylperoxide (1.18 g, 8.06 mmol)
in 1/1 toluene/ethanol (10 mL) was bubbled with N2 with
stirring for 10 min and then NaBH4 (610 mg, 16.1 mmol)
was added. After stirring for 18 h, the mixture was evapo-
rated to dryness and portioned between chloroform
(50 mL) and water (50 mL). The organic layer was sepa-
rated and the aqueous layer was extracted with chloroform
(20 mL ꢁ 3). The combined organic layers were dried over
sodium sulfate and evaporated to dryness. The residue was
purified by column chromatography on silica gel, eluting
with 16:1 hexane/dichloromethane gradually increasing
to 9:1 to give 5 (1.48 g, 55.6%) as a colorless oil. Data
for 5: Rf ¼ 0.25 (hexane/dichloromethane, 9: 1); 1H NMR
C
19H30NNaOSi [M þ Na]þ 339.1988: found 338.1937.
2,2,5-Trimethyl-3-(1-(40-chloromethyl)phenylethoxy)-
4-(30-(trimethylsilyl)ethynyl)phenyl-3-azahexane (5)
A mixture of 4 (1.70 g, 5.37 mmol), p-vinylbenzylchloride
(1.60 g, 10.7 mmol), (R,R)-(ꢀ)-N,N0-bis(3,5-di-tert-butylsalicy1i-
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ARTICLE
(400 MHz, CDCl3) (both diastereomers):
d
7.55–7.07
4-(1-(tert-Butyl-(2-methyl-1-(30-(trimethylsilylethynyl)
(m, 16H, phenyl-H, both diastereomers), 4.91 (q, 3J ¼ 6.5
Hz, 2H, CHON, both diastereomers), 4.59 (s, 2H, CH2Cl,
minor diastereomer), 4.56 (s, 2H, CH2Cl, major diaster-
eomer), 3.40 (d, 1H, 3J ¼ 10.8 Hz, CH, 4.59, major diaster-
eomer), 3.29 (d, 1H, 3J ¼ 10.8 Hz, CH, minor diaster-
eomer), 2.3 and 1.3 (m, 1H, CH, both diastereomers), 1.62
(d, 3H, 3J ¼ 6.5 Hz, CH3, major diastereomer), 1.54 (d, 3H,
3J ¼ 6.5 Hz, CH3, minor diastereomer), 1.28 (d, 3H, 3J ¼
6.4 Hz, CH3, major diastereomer), 1.05 (s, 9H, NCCH3,
minor diastereomer), 0.93 (d, 3H, 3J ¼ 6.4 Hz, CH3, minor
diastereomer), 0.79 (s, 9H, NCCH3, major diastereomer),
0.54 (d, 3H, 3J ¼ 6.6 Hz, CH3), 0.26 (s, 18H, SiCH3, both
diastereomer), 0.22 (d, 3H, 3J ¼ 6.8 Hz, CH3, minor dia-
stereomer); 13C NMR (100 MHz, CDCl3) (both diastereom-
ers): d 145.73 (phenyl-C), 145.01 (phenyl-C), 142.35 (phe-
nyl-C), 142.15 (phenyl-C), 136.50 (phenyl-C), 135.82
(phenyl-C), 134.58 (phenyl-CH), 134.45 (phenyl-CH), 131.30
(phenyl-CH), 131.26 (phenyl-CH), 130.11 (phenyl-CH),
129.97 (phenyl-CH), 128.40 (phenyl-CH), 128.38 (phenyl-
CH), 127.34 (phenyl-CH), 127.31 (phenyl-CH), 126.52 (phe-
nyl-CH), 122.09 (phenyl-C), 121.89 (phenyl-C), 105.92 (phe-
nyl-C:), 93.27 (:C-Si), 83.20 (CH), 82.40 (CH), 71.91
(NCH), 71.82 (NCH), 60.77 (NC), 46.29 (CH2Cl), 46.27
(CH2Cl), 32.11 (CH), 31.78 (CH), 28.65 (CH3) 28.47 (CH3),
24.69 (CH3), 23.07 (CH3), 22.24 (CH3), 22.05 (CH3), 21.29
(CH3), 21.20 (CH3), 0.31 (SiCH3), 0.29 (SiCH3); IR (cmꢀ1):
m 2959, 2869, 2156, 1596, 1481, 1421, 1387, 1361, 1263,
1249, 1206, 1060, 856, 840, 797, 759, 704, 647; ESI-TOF
phenylpropyl)aminooxy)ethyl)benzyl 4-Azidobenzoate (7)
To a solution of 5 (1.06 g, 2.66 mmol) and 4-azidobenzoic
acid (6) (692 mg, 4.25 mmol) in hexamethylphosphoric acid
triamide (HMPA, 1.0 mL), cesium carbonate (Cs2CO3, 953
mg, 5.32 mmol) was added and the mixture was stirred for
48 h at room temperature. The mixture was evaporated to
dryness and partitioned between dichloromethane (100 mL)
and water (100 mL). The organic layer was separated and
the aqueous layer was extracted with dichloromethane
(50 mL ꢁ 3). The combined organic layers were dried over
sodium sulfate and evaporated to dryness. The residue was
purified by column chromatography on silica gel, eluting
with 9: 1 hexane/dichloromethane increasing to 1: 1 to give
7 (1.26 g, 79.4%) as a yellowish viscous liquid. Data for 7:
Rf
¼
0.47 (hexane/dichloromethane, 1: 1); 1H NMR
(400 MHz, CDCl3) (both diastereomers): d 8.04 (d, 4H, 3J ¼
8.7 Hz, phenyl-H, both diastereomers), 7.60-7.02 (m, 20H,
phenyl-H, both diastereomers), 5.34 (s, 2H, CH2O, major dia-
stereomer), 5.31 (s, 2H, CH2O, minor diastereomer), 4.96 (m,
2H, CHON, both diastereomers), 3.41 (d, 1H, 3J ¼ 10.8 Hz,
NCH, minor diastereomer), 3.29 (d, 1H, 3J ¼ 10.8 Hz, NCH,
major diastereomer), 2.3 and 1.3 (m, 2H, CH, both diaster-
3
eomers), 1.62 (d, 3H, J ¼ 6.5 Hz, CH3, minor diastereomer),
1.54 (d, 3H, 3J ¼ 6.5 Hz, CH3, major diastereomer), 1.26
(d, 3H, 3J ¼ 6.2 Hz, CH3, minor diastereomer), 1.04 (s, 9H,
NCCH3, major diastereomer), 0.91 (d, 3H, 3J ¼ 6.4 Hz, CH3,
major diastereomer), 0.70 (s, 9H, NCCH3, minor diaster-
eomer), 0.54 (d, 3H, 3J ¼ 6.4 Hz, CH3, minor diastereomer),
3
MS exact mass calcd for
470.2640: found 470.2613.
C
28H41ClNOSi [M
þ
H]þ
0.24 (s, 18H, SiCH3, both diastereomer), 0.19 (d, 3H, J ¼ 6.4
Hz, CH3, major diastereomer); 13C NMR (100 MHz, CDCl3)
(both diastereomers): d 165.59 (C ¼¼ O), 165.56 (C ¼¼ O),
145.61 (phenyl-C), 144.92 (phenyl-C), 144.83 (phenyl-C),
142.38 (phenyl-C), 142.20 (phenyl-C), 134.98 (phenyl-C),
134.62 (phenyl-CH), 134.50 (phenyl-CH), 134.31 (phenyl-C),
131.55 (phenyl-CH), 131.53 (phenyl-CH), 131.28 (phenyl-
CH), 130.12 (phenyl-CH), 129.97 (phenyl-CH), 128.03 (phe-
nyl-CH), 128.00 (phenyl-CH), 127.27 (phenyl-CH), 127.15
(phenyl-CH), 126.78 (phenyl-C), 126.41 (phenyl-CH), 122.08
(phenyl-C), 121.87 (phenyl-C), 118.84 (phenyl-CH), 105.90
(phenyl-C:), 93.23 (:C-Si), 93.01 (:C-Si), 83.19 (CH),
82.47 (CH), 71.85 (CH), 71.76 (CH), 66.71 (CH2O), 60.72
(NC), 32.01 (CH), 31.68 (CH), 28.54 (CH3) 28.38 (CH3),
24.67 (CH3), 22.97 (CH3), 22.15 (CH3), 21.94 (CH3), 21.17
(CH3), 21.09 (CH3), 0.16 (SiCH3); IR (cmꢀ1): m 2959, 2869,
2114, 1719, 1603, 1504, 1481, 1362, 1249, 1206, 1173,
1130, 1098, 1060, 841, 764, 734, 704, 647; ESI-TOF MS
exact mass calcd for C35H45N4NaO3Si [M þ Na]þ 619.3074:
found 619.2655.
4-Azidobenzoic Acid (6)
4-Azidobenzoic acid (6) was prepared similar to the litera-
ture procedure.44 To a suspension of 4-aminobenzoic acid
(4.50 g, 32.8 mmol) in water (25 mL) in a 2 L beaker, con-
centrated hydrochloric acid (5.60 mL) was added dropwise
with vigorously stirring. Then an aqueous solution of sodium
nitrite (2.26 g, 32.8 mmol) in water (10 mL) was slowly
added with cooling in an ice bath. The color of the suspension
changed to orange-yellow during the addition. After this an
aqueous solution of sodium azide (2.13 g, 32.8 mmol) in
water (25 mL) was slowly added, water (100 mL) and ethyl
acetate (125 mL) were added, the organic layer was sepa-
rated, and the aqueous layer was extracted with ethyl acetate
(50 mL ꢁ 3). The combined organic layers were extracted
with 1N sodium hydroxide aqueous solutions (40 mL ꢁ 2)
and then the aqueous extracts were acidified with 1N hydro-
chloride aqueous solution (80 mL). The mixture was extracted
with ethyl acetate (50 mL ꢁ 3), and the combined extracts
were dried over sodium sulfate and evaporated to dryness to
4-(1-(tert-Butyl-(2-methyl-1-(30-ethynylphenyl-propyl)
aminooxy)ethyl)benzyl 4-Azidobenzoate (1)
1
give 6 (4.70 g, 87.8%) as a yellow solid. Data for 6: H NMR
3
(400 MHz, CDCl3): d 8.09 (d, J ¼ 8.4 Hz, 2H, phenyl-H), 7.09
TBAF (1 M THF solution, 1.87 mL) was added to a solution
of 7 (1.26 g, 2.40 mmol) in dry dichloromethane (10 mL).
After stirring for 30 min at room temperature, water
(10 mL) was added. The organic layer was separated, and
the aqueous layer was extracted with dichloromethane
(20 mL ꢁ 3). The combined organic layers were dried over
(d, 3J ¼ 8.4 Hz, 2H, phenyl-H); 13C NMR (100MHz, CDCl3): d
170.43 (C¼¼O), 145.68 (phenyl-C), 132.06 (phenyl-C), 125.66
(phenyl-CH), 119.00 (phenyl-CH); IR (cmꢀ1): m 2959, 2541,
2101, 1672, 1600, 1577, 1507, 1424, 1330, 1317, 1281, 1177,
1138, 1121, 933, 859, 831, 779, 765, 690.
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JOURNAL OF POLYMER SCIENCE: PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
SCHEME 2 a) Synthesis of a nitroxide radical with a trimethylsilyl (TMS)-protected acetylene 4 through i) the reaction of (2-(30-bro-
mophenyl)ethynyl)trimethylsilane with magnesium (Mg) in dry THF to prepare a Grignard reagent, ii) the reaction with N-tert-
butyl-a-isopropylnitrone, and iii) aerial oxidation using copper(II) acetate (Cu(OAc)2) in MeOH and 25% ammonium hydroxide solu-
tion and b) synthesis of the acyclic alkoxyamine derivative featuring an azide and a terminal alkyne 1 (structure; see Scheme 1)
through iv) the reaction of 4 with p-vinylbenzylchloride using (R,R)-(ꢀ)-N,N0-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanedia-
mino manganese(III) chloride, di-tert-butylperoxide, and sodium borohydride in 1:1 toluene/ethanol to prepare a alkoxyamine de-
rivative containing chloromethyl group and trimethylsilyl (TMS)-protected acetylene 5, v) esterification of 5 with 4-azidobenzoic
acid 6 using cesium carbonate (Cs2CO3) in hexamethylphosphoric acid triamide (HMPA) to prepare alkoxyamine derivatives bear-
ing 4-azidobenzoate and TMS-protected acetylene 7, and vi) deprotection of the TMS group using TBAF in dry dichloromethane.
sodium sulfate and evaporated to dryness. The residue was
purified by flush column chromatography on silica gel with
1:1 hexane/dichloromethane to give 1 (1.00 g, 79.6%) as a
yellowish viscous liquid. Data for 1: Rf ¼ 0.39 (hexane/
(phenyl-CH), 121.04 (phenyl-C), 120.83 (phenyl-C), 118.84
(phenyl-CH), 84.37 (phenyl-C:), 84.31 (phenyl-C:), 83.29
(CH), 82.47 (CH), 76.52 (C:H), 76.38 (C:H), 71.88 (CH),
71.81 (CH), 66.77 (CH2O), 66.75 (CH2O), 60.74 (NC), 32.11
(CH), 31.82 (CH), 28.62 (CH3) 28.45 (CH3), 24.75 (CH3),
23.10 (CH3), 22.21 (CH3), 22.03 (CH3), 21.27 (CH3), 21.16
(CH3); IR (cmꢀ1): m 3299, 2974, 2869, 2113, 1717, 1603,
1504, 1362, 1304, 1267, 1206, 1173, 1130, 1097, 1060,
1014, 850, 825, 765, 702; ESI-TOF MS exact mass calcd for
1
dichloromethane, 1: 1); H NMR (400 MHz, CDCl3) (both dia-
3
stereomers): d 8.05 (d, 2H, J ¼ 8.4 Hz, phenyl-H, minor dia-
3
stereomer), 8.04 (d, 2H, J ¼ 8.4 Hz, phenyl-H, major diaster-
eomers), 7.60-7.02 (m, 20H, phenyl-H, both diastereomers),
5.34 (s, 2H, CH2O, major diastereomer), 5.31 (s, 2H, CH2O,
minor diastereomer), 4.93 (m, 2H, CHON, both diastereom-
ers), 3.43 (d, 1H, 3J ¼ 10.4 Hz, NCH, minor diastereomer),
3.30 (d, 1H, 3J ¼ 10.4 Hz, NCH, major diastereomer), 3.32
(s, 1H, CBH, major diastereomer), 3.29 (s, 1H, CBH, minor
diastereomer), 2.3 and 1.4 (m, 2H, CH, both diastereomers),
1.62 (d, 3H, 3J ¼ 6.8 Hz, CH3, minor diastereomer), 1.54
(d, 3H, 3J ¼ 6.4 Hz, CH3, major diastereomer), 1.27 (d, 3H,
3J ¼ 6.4 Hz, CH3, minor diastereomer), 1.04 (s, 9H, NCCH3,
major diastereomer), 0.92 (d, 3H, 3J ¼ 6.8 Hz, CH3, major
diastereomer), 0.80 (s, 9H, NCCH3, minor diastereomer), 0.54
(d, 3H, 3J ¼ 6.4 Hz, CH3, minor diastereomer), 0.20 (d, 3H,
3J ¼ 6.8 Hz, CH3, major diastereomer); 13C NMR (100 MHz,
C
32H36N4NaO3 [M þ Na]þ 547.2679: found 547.2292.
Cyclic NMP-Initiator (2)
Tetrakis(acetonitrile)copper(I) hexafluorophosphate ([(CH3CN)4Cu]
PF6), 169 mg, 0.453 mmol) was added to a mixture of 1 (1.00
g, 1.91 mmol), tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]-
amine (TBTA, 240 mg, 0.452 mmol) and N-ethyldiisopropyl-
amine (DIPEA, 1.76 g, 13.6 mmol) in DMF (60.0 mL). After
stirring for 48 h, the mixture was evaporated to dryness and
the residue was purified by column chromatography on silica
gel with 4: 1 hexane/ethyl acetate to give 2 (191 mg, 19.1%)
as a slightly yellowish solid. Data for 2: Rf ¼ 0.31 (hexane/
1
CDCl3) (both diastereomers):
d
165.53 (C¼¼O), 165.50
ethyl acetate, 4: 1); H NMR (500 MHz, 1,1,1,3,3,3-hexafluoro-
(C¼¼O), 145.57 (phenyl-C), 144.81 (phenyl-C), 142.47 (phe-
nyl-C), 142.22 (phenyl-C), 134.98 (phenyl-CH), 134.75 (phe-
nyl-C), 134.71 (phenyl-CH), 134.30 (phenyl-CH), 131.62
(phenyl-CH), 131.52 (phenyl-CH), 131.49 (phenyl-CH),
130.23 (phenyl-CH), 130.03 (phenyl-CH), 128.11 (phenyl-
CH), 128.03 (phenyl-CH), 127.37 (phenyl-CH), 127.24 (phe-
nyl-CH), 127.18 (phenyl-CH), 126.77 (phenyl-C), 126.39
2-propanol-d2) (both diastereomers): d 8.38-7.04 (m, 26H,
phenyl-H and triazole-H), 5.60-4.82 (m, 6H, CH2O and CHON),
4.04-3.80 (br, 2H, NCH), 3.30-2.10 (br, 2H, CH), 1.90-1.60
(m, 6H, CH3), 1.50-0.80 (m, 30H, CH3 and NCCH3); 13C NMR
(125 MHz, 1,1,1,3,3,3-hexafluoro-2-propanol-d2) (both diaster-
eomers): d 170.00-169.00 (C¼¼O), 153.00-152.00 (triazole-C),
142.38 (phenyl-C), 142.26 (phenyl-C), 141.50 (phenyl-C),
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ARTICLE
133.80-133.20 (phenyl-CH), 132.40-131.80 (phenyl-C), 131.23
(phenyl-CH), 130.32 (phenyl-CH), 130.10-129.80 (phenyl-CH),
129.60-128.40 (triazole-CH), 127.21 (phenyl-CH), 126.07(phe-
nyl-C), 126.03 (phenyl-C), 125.99 (phenyl-C), 125.37 (phenyl-C),
125.27 (phenyl-C), 125.18 (phenyl-C), 123.92 (phenyl-C), 123.86
(phenyl-C), 123.82 (phenyl-C), 123.06 (phenyl-C), 122.95 (phe-
nyl-C), 122.85 (phenyl-C), 122.70 (phenyl-C), 121.74 (phenyl-C),
121.70 (phenyl-C), 121.64 (phenyl-C), 120.74 (phenyl-C), 120.63
(phenyl-C), 120.53 (phenyl-C), 70.00-69.50 (CH2O), 31.70-30.60
(CH3), 25.80-23.60 (CH3), 23.00-20.20 (CH3). IR (cmꢀ1): m 2972,
2870, 1722, 1608, 1518, 1408, 1363, 1310, 1272, 1217, 1149,
1107, 1015, 985, 856, 812, 789, 766, 692, 663. MALDI-TOF MS
exact mass calcd for C32H37N4O3 [M þ H]þ 525.3: found 524.9.
Polymerization
Typically, the cyclic initiator 2 (18.8 mg, 0.0358 mmol) was
dissolved in 1,1,1,3,3,3-hexafluoro-2-phenyl-2-isopropanol
(HFPP) (1.49 g) and then styrene (St) (746 mg, 7.17 mmol)
was added. The mixture was subjected to three freeze-thaw
cycleꢂs, sealed under argon, and immersed in an oil bath at
125 C for 6 h with stirring. After cooling in liquid nitrogen,
the mixture was diluted with THF (5 mL) and then poured
into methanol (300 mL). The precipitate was purified by rep-
recipitation with THF-methanol and dried in vacuo to give 3
(360 mg, 45.7%) as a white powder. Data for 3: 1H NMR
(500 MHz, CDCl3): d 8.40-6.23 (br, phenyl-H), 5.45-5.23 (br,
CH2O), 2.60-1.20 (br, CH and CH2 in the main chain), 1.20-
0.06 (br, CH3); IR (cmꢀ1): m 3083, 3060, 3026, 2922, 2850,
1724, 1602, 1493, 1452, 1366, 1272, 1069, 1028, 755, 696;
Mn ¼ 52,200 g molꢀ1, Mw/Mn ¼ 2.35.
Hydrolysis
To a solution of 3 (61.1 mg) in THF (2 mL), a THF solution
containing 10 wt % methanolic potassium hydroxide (KOH)
(2.00 mL) was added. After stirring for 12 h at 40 ꢂC,
aqueous hydrochloric acid solution (1N, 5.00 mL) was
added and the mixture was extracted with dichloromethane
(10 mL ꢁ 2). The combined organic layers were washed
with water (10 mL), dried over sodium sulfate, evaporated
to dryness, redissolved in THF (1 mL), and poured into
methanol (50 mL). The precipitate was filtered and dried in
vacuo to give 8 as the main product (56.7 mg, 92.8%). Data
FIGURE
1,1,1,3,3,3-hexafluoro-2-isopropanol-d2 (HFIP-d2).
1 1 in CDCl3 and b) 2 in
1H NMR spectra of a)
CH2 in the main chain), 1.20-0.06 (br, CH3); IR (cmꢀ1): m
3083, 3060, 3026, 2924, 2850, 1602, 1493, 1452, 1029, 756,
696; Mn ¼ 13,300 g molꢀ1, Mw/Mn ¼ 2.12.
1
for 8: H NMR (500 MHz, CDCl3): d 8.40-6.23 (br, phenyl-H),
4.70-4.55 (br, CH2O), 2.60-1.20 (br, CH and CH2 in the
Matrix-Assisted Laser Desorption/Ionization
Time-of-Flight Mass Spectrometer
main chain), 1.20-0.06 (br, CH3); IR (cmꢀ1): m 3083, 3060,
3026, 2922, 2850, 1602, 1493, 1452, 1028, 755, 696; Mn
13,400 g molꢀ1, Mw/Mn ¼ 2.08.
¼
MALDI-TOF-MS analyses were performed using Bruker Dalto-
nik Autoflex III instrument. This instrument is equipped with
an Nd:YAG laser (335 nm) and a delayed pulse extraction
(0 or 100 ns). It was operated at an accelerating potential of
5.5 kV in a linear mode. The instrument was calibrated with
Radical Crossover Reaction
Acyclic alkoxyamine 5 (25.0 mg, 0.0532 mmol) and 3 (50.3
mg) were dissolved in HFPP (640 mg). The mixture was sub-
jected to three freeze-thaw cycles, sealed under argon, and
a poly(ethylene glycol) (PEG) standard (Mp ¼ 4200 g molꢀ1
,
Mw/Mn ¼ 1.02) using a four-point calibration. The solutions
of 2, 3, and 8 in THF were prepared (2–5 g Lꢀ1) in a similar
manner. The matrix solution was prepared by dissolving 1,8-
dihydroxy-9(10H)-anthracenone (dithranol) in THF (10 g
ꢂ
immersed in an oil bath at 125 C for 6 h with stirring. After
cooling, the mixture was diluted with THF (1 mL) and then
poured into methanol (50 mL). The precipitate was filtered
and dried in vacuo to give 9 as the main product (50.9 mg,
96.0%). Data for 9: 1H NMR (500 MHz, CDCl3): d 8.40-6.23
(br, phenyl-H), 5.45-5.23 (br, CH2O), 2.60-1.20 (br, CH and
L
ꢀ1). A silver trifluoroacetate (AgTFA) solution in THF was
prepared in a concentration of (10 g Lꢀ1); sodium iodide
(NaI) solution in methanol was prepared in a concentration
CYCLIC ALKOXYAMINE ENABLING RING-EXPANSION VINYL POLYMERIZATION, NARUMI ET AL.
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JOURNAL OF POLYMER SCIENCE: PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
GMHHR-N column (column temperature, 22 ꢂC; column size,
7.8 mm ꢁ 300 mm; particle size, 5 lm; exclusion limit, 4 ꢁ
105) using THF as an eluent at a flow rate of 1.0 mL minꢀ1
.
The Mn, Mw/Mn, and Mp were determined on the basis of a
polystyrene calibration. Type II: Quadruple-detector GPC was
performed using a Viscotek GPCmax VE-2001 equipped with
a Viscotek Model 302-040 Triple Detector Array and a Well-
Chrom Spectro-Photometer K-2501 (wavelength, 254 nm)
and two columns consisting of a Viscotek GMHHR-N Mixed
Bed column (column temperature, 35 ꢂC; column size, 7.8
mm ꢁ 300 mm; particle size, 5 lm; exclusion limit, 4 ꢁ 105)
and a Viscotek G2500 HHR column (column temperature 35
ꢂC, 7.8 mm ꢁ 300 mm; particle size, 5 lm, exclusion limit, 2
ꢁ 104) using THF as an eluent at a flow rate of 1.0 mL
minꢀ1. Polystyrenes with the Mn of 6220 and 99,209 g
molꢀ1 and the Mw/Mn of 1.05 and 1.02, respectively, were
used for the calibrations of the detector. The Mn, Mw/Mn, and
Mp were determined on the basis of a polystyrene calibration
and the dn/dc of 0.185 was used for the light scattering (LS)
analyses.
FIGURE 2 APT spectra of a) 1 in CDCl3 and b) 2 in 1,1,1,3,3,3-
hexafluoro-2-isopropanol-d2 (HFIP-d2).
of (10 g Lꢀ1). The final sample solutions were prepared as
follows; method I: a solution of 2 (100 lL) was mixed with
the matrix solution (100 lL) and AgTFA solution (5 lL).
Method II: a solution of 3 (20 lL) was mixed with the matrix
solution (100 lL) and AgTFA solution (2 lL). Method III: a
solution of 8 (100 lL) was mixed with the matrix solution
(10 lL) and NaI solution (10 lL). A 0.5 (L portion of the re-
spective final sample solutions has then deposited on the
sample target and allowed to air-dry at room temperature.
The spectra were obtained by collecting 2000–5000 shots
(100 Hz repetition rate). All spectra were baseline corrected
and smoothed using a three-point Savitzky-Golay algorithm.
Gel Permeation Chromatography
The number-average molecular weight (Mn), molecular
weight distribution (Mw/Mn), and molecular weight at the
peak top (Mp) were determined by two types of GPC appara-
tus in this study. Type I: A routine GPC was performed using
a Viscotek VE 2001 equipped with a Viscotek VE 3580 RI
detector (detector temperature, 35 ꢂC) and a Viscotek
FIGURE 3 IR spectra of a) 1 and b) 2.
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ARTICLE
assignable to its structure appear. The dashed alphabets in
Figures 1(a) and 2(a) assign the resonances due to the
minor diastereomers. Figure 3(a) shows the IR spectrum of
1, exhibiting the strong peaks due to terminal alkyne, azide,
and ester group at 3299, 2113, and 1717 cmꢀ1, respectively.
The cyclization of 1 was performed using the azide/alkyne-
‘‘click’’-reaction with tetrakis(acetonitrile)copper(I) hexafluor-
ophosphate ([(CH3CN)4Cu]PF6) as the copper source, N-ethyl-
diisopropylamine (DIPEA) as the base, and tris[(1-benzyl-1H-
1,2,3-triazol-4-yl)methyl]amine (TBTA) as the cocatalyst in
FIGURE 4 MALDI-TOF MS spectrum of 2.
RESULTS AND DISCUSSION
Synthesis and Characterization of Cyclic NMP-Initiator
The structure of the alkoxyamine derivative featuring an
azide and a terminal alkyne, acyclic precursor for azide/
alkyne-‘‘click’’-reaction 1, is illustrated in Scheme 1. To syn-
thesize the precursor, a nitroxide radical with a trimethylsilyl
(TMS)-protected acetylene 4 was first prepared through
the similar reactions reported by Hawker and coworkers36
and our group45 (Scheme 2a). (2-(30-Bromophenyl)ethynyl)-
trimethylsilane was transformed into the Grignard reagent in
dry THF and reacted with N-tert-butyl-a-isopropylnitrone,
followed by aerial oxidations using copper(II) acetate. The
target 4 could be isolated as viscous orange oils, whereas it
should be noted that the prolonged refluxing during the
preparation of the Grignard reagent was shown to remove
the TMS-protecting group.
The obtained nitroxide radical 4 was reacted with p-vinyl-
benzylchloride using (R,R)-(ꢀ)-N,N0-bis(3,5-di-tert-butylsali-
cy1idene)-1,2-cyclohexanediaminomanganese(III)
chloride,
di-tert-butylperoxide, and NaBH4 to yield the alkoxyamine
derivative 5 containing the p-chloromethyl group and the 30-
TMS-protected acetylene as a colorless oil (Scheme 2b). Sub-
sequently, 5 was modified by esterification with 4-azidoben-
zoate 6 using cesium carbonate in hexamethylphosphoric
acid triamide (HMPA) similar to a previous modification
using ‘‘click’’-chemistry reported in our laboratory,45 produc-
ing the alkoxyamine derivative 7 bearing an 4-azido benzo-
ate and TMS-protected acetylene. Afterwards, the TMS group
was removed using TBAF producing the target acyclic pre-
cursor 1. Figures 1(a) and 2(a) show the 1H NMR and APT
spectra for 1, respectively, in which the characteristic signals
FIGURE 5 GPC traces of the products obtained by the polymer-
izations of styrene (St) in 1,1,1,3,3,3-hexafluoro-2-phenyl-2-pro-
panol (HFPP) with a) 5 using the [M]/[I] of 50: 1, b) 2 using the
[M]/[I] of 50:1, c) 2 using the [M]/[I] of 200:1, and d) 2 using the
[M]/[I] of 1000:1.
CYCLIC ALKOXYAMINE ENABLING RING-EXPANSION VINYL POLYMERIZATION, NARUMI ET AL.
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JOURNAL OF POLYMER SCIENCE: PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
FIGURE 6 1H NMR spectra of a)
the product obtained through
the polymerization of styrene
(St) with 2 using the [M]/[I] of
50:1 in CDCl3, and b) the product
after the hydrolysis of 3 with the
molecular weight at the peak top
(Mp) for the main peak of
121,000 g molꢀ1 using methano-
lic KOH in THF in CDCl3.
DMF under high dilution conditions (Scheme 1). After com-
pound 1 was consumed as judged by TLC (Rf ¼ 0.39, hexane/
dichloromethane ¼ 1: 1), the reaction mixture was evaporated
and purified by column chromatography to yield product 2 (Rf
¼ 0.31, hexane/ethyl acetate ¼ 4: 1) in 19.0% isolated yield.
Product 2 was not soluble in common organic solvents indica-
tive of its cyclic structure due to the restrictions of molecular
mobilities within the cycle. However, 2 was found to show
good solubility in fluorinated alcohols, thus enabling NMR
analyses in 1,1,1,3,3,3-hexafluoro-2-propanol-d2 (HFIP-d2).
The resonances of the H NMR spectrum for 2 were complex,
however, assignable to the target structure as displayed in
1
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ARTICLE
Polymerization of Styrene with Cyclic NMP-Initiator
and Characterizations of the Products to Reveal the
Mechanisms of the System
We next focused on the polymerization of styrene (St) with
cyclic NMP-initiator 2. Initial experiments were tried, poly-
merizing St in bulk at 125 ꢂC. However, the initiator 2 was
not soluble in St even at the polymerization temperature and
thus the polymerization proceeded heterogeneously and was
not pursued further. As we found out that 2 was soluble in
fluorinated alcohols, a fluorinated alcohol with a high boiling
point, such as HFPP, was used as a solvent. To prove the
influence of the fluorinated solvent on the NMP-process, St
was first polymerized with the acyclic alkoxyamine 5 in
HFPP using a monomer/initiator-ratio ([M]/[I]) of 50: 1,
which afforded the PSt-polymer in 49.9% yield. Figure 5(a)
shows the GPC trace of the resulting linear product, exhibit-
ing a monodisperse peak with the number-average molecular
weight (Mn) and the molecular weight distribution (Mw/Mn)
of 3400 g molꢀ1 and 1.11, respectively, in which the Mn was
consistent with the theoretical molecular weight (Mn,th) of
3100 g molꢀ1. Hence, the use of HFPP as the solvent did not
negatively affect the system during the polymerization reac-
tion. However, the terminal trimethylsilyl acetylene moiety
1
was cleaved off as indicated by the IR and H NMR measure-
ments, presumably due to the use of the slightly acidic sol-
vent such as HFPP.
SCHEME 3 Schematic illustration for the radical ring-crossover
reactions generating macrocyclic PSt with a more expanded
ring. The polymer contains multiple units derived from the
cyclic initiator.
Subsequently similar polymerizations were performed
using cyclic alkoxyamine-initiator 2 in HFPP as the solvent
(Scheme 1), which now homogeneously proceeded to pro-
duce a PSt-polymer in 46.3% yield. Figure 5(b) shows the
GPC trace of the PSt-product formed after initiation by the
cyclic NMP-initiator 2. It should be emphasized that the trace
[Fig. 5(b)] drastically differed from that obtained by using
the acyclic alkoxyamine 5 [Fig. 5(a)]. The trace of PSt-poly-
mer via 2 exhibits bimodal peaks with the Mn ¼ 15,800 g
molꢀ1 and Mw/Mn ¼ 2.62. The peak top (Mp)-values of the
main peak and the shoulder in the lower molecular weight
regions were 37,000 g molꢀ1 and 3700 g molꢀ1, respectively.
The Mp of 3700 g molꢀ1 was close to calculated value for
cyclic PSt with one initiator unit of 2935 g molꢀ1, whereas
the system was shown to produce a polymer with consider-
ably higher molecular weights. Similar results were observed
for the polymerizations using a monomer/initiator-ratio of
[M]/[I] ¼ 200: 1. The polymerization was demonstrated with
2 in HFPP for 6 h to produce a polymer in the 45.7%. Figure
5(c) displays the GPC trace of the product, in which the Mn
and Mw/Mn were 52,200 g molꢀ1 and 2.35, respectively, with
Mp values of the main peak and the shoulder of 121,000 and
8500 g molꢀ1, respectively. Thus, the molecular weights of
the products increased with the increasing [M]/[I] ratios.
Figure 1(b). Notably, the respective signals are broadened as
compared to those of 1, possibly due to the presence of re-
stricted motions for the protons within the cyclized structures.
Figure 2(b) shows the APT spectrum for 2. The resonances
due to the methine and quaternary carbons in the alkoxy-
amine backbones were not detected due to the low S/N ratio,
whereas the resonances derived from the methyl carbons
clearly appeared at the region from 32 to 20 ppm. Resonances
due to the benzoate moiety were observed at the regions from
170 to 169 ppm and from 143 to 141 ppm. In addition, the
resonances of the triazole-carbons appeared at the region from
153 to 152 ppm, thus proving that 2 was indeed the product
formed via the azide/alkyne-‘‘click’’ reaction. Figure 4 displays
the MALDI-TOF MS of 2, exhibiting the main peak at m/z ¼
524.9, which was consistent with the calculated [M þ H]þ value
for the target cyclic alkoxyamine of 525.3. Another peak also
appeared at m/z ¼ 1049.2 implying that a dimeric byproduct
was also generated via an intermolecular addition reaction,
even though the reaction was performed using a high dilution
conditions as is required for the intramolecular cyclization.
However, both adsorptions due to the azide- and alkyne-moi-
eties disappeared in the IR spectrum of 2 [Fig. 3(b)], excluding
significant contaminations of 2 with acyclic byproducts. These
results indicated that 2 was assignable to the target cyclic
alkoxyamine tethered by the benzoate- and the 1,2,3-1H-tria-
zole ring as illustrated in Scheme 1, taking into account the con-
tamination with a small amount of the cyclic dimer.
Using
a
monomer/initiator-ratio of [M]/[I]
¼
1000/1
afforded PSt-product in 43.4% yield, with Mn ¼ 65,300 g
molꢀ1 and Mw/Mn ¼ 2.75 as shown in Figure 5(d). The Mp
values of the main peak and the shoulder were 147,000 and
10,000 g molꢀ1, respectively. Therefore, the system with the
cyclic NMP-initiator produced polymers with significantly
high molecular weights, indicating that this system is
CYCLIC ALKOXYAMINE ENABLING RING-EXPANSION VINYL POLYMERIZATION, NARUMI ET AL.
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JOURNAL OF POLYMER SCIENCE: PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
FIGURE 7 MALDI-TOF MS spec-
tra of a) the product obtained by
the polymerizations of styrene
(St) in 1,1,1,3,3,3-hexafluoro-2-
phenyl-2-propanol (HFPP) with 2
using [M]/[I] of 50:1 and b) the
product after the hydrolysis of 3
with the molecular weight at the
peak top (Mp) for the main peak
of 121,000 g molꢀ1 using metha-
nolic KOH in THF in CDCl3.
accompanied with different/additional reaction-pathways as
compared to that with the acyclic initiator. The pathways
should include radical ring-crossover reactions, which will be
later described.
exchange of mediated nitroxide,35,46–48 as illustrated in
Scheme 3, could occur to generate a macrocyclic PSt with a
more expanded ring or linear PSt polymers.
Characterization of the Products Obtained Through the
Polymerization of Styrene with Cyclic NMP-Initiator by
MALDI-TOF MS
Figure 6(a) shows the 1H NMR of the PSt-product formed
after polymerization with the [M]/[I] of 50:1. The large
resonances derived from protons due to PSt appeared that
included aromatic ones at the region from 7.4 to 6.2 ppm
and methine and methylene ones in the main chains at the
region from 2.2 to 1.2 ppm. Additionally, the characteristic
signals due to the unit derived from cyclic initiator 2 clearly
appeared. For examples, aromatic protons in the benzoate
linkage, methylene protons adjacent to the ester group, and
methyl protons in the alkoxyamine moiety were observed at
the regions from 8.3 to 8.1 ppm, from 5.5 to 5.3 ppm, and
from 1.2 to 0.1 ppm, respectively. In the IR spectrum of the
product, the distinct peak of the carbonyl group derived
from 2 appeared at 1724 cmꢀ1. These results suggested that
the products were assignable to PSt’s initiated by 2. Thus,
we propose that this polymerization system proceeds by the
ring-expansion polymerization mechanism to produce PSt-
monocycle as shown in Scheme 1. Simultaneously, radical
ring-crossover reactions originating from the inherent
Figure 7(a) shows the MALDI-TOF MS of the product
obtained through the polymerization of St with 2 using the
[M]/[I] ratio of 50:1. The spectrum exhibits a series of
major peaks in the area of m/z ranging from 3200 to 8000
with a regular interval of 104.1 corresponding to the mass
of the St repeating unit. Although the observed peaks were
due to the low molecular weight species considering that
the Mn and Mw/Mn of this sample were 15,800 g molꢀ1
and 2.62, respectively, the m/z values of the peaks were
consistent with those of a PSt with one initiator-unit. To
state one example, the m/z of 4191.5 corresponds to the
[M þ Na]þ of 35-mer PSt-monocycle, which completely
agrees with the calculated value for C312H315N4O3Na of
4191.5. In addition, one of the series of minor peaks was
also assignable to PSt-monocycle. As an example, the m/z
of 4170.8 was derived from the [M þ H]þ of a 35-mer PSt,
being consistent with the calculated value for C312H316N4O3
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ARTICLE
FIGURE 8 GPC traces of macro-
cyclic polystyrenes 3 obtained by
the polymerizations of styrene
(St) in 1,1,1,3,3,3-hexafluoro-2-
phenyl-2-propanol (HFPP) with 2
using the [M]/[I] ratios of a) 50:1,
b) 200:1, and c) 1000:1, which
were detected by the RI, UV, IV,
and LALS, and RALS detectors.
of 4170.9. Therefore, PSt’s with cyclic structures should be
produced in the present system via the mechanism as
shown in Chart 1. Other series of small peaks are not
assigned because various possible peaks that include those
derived from cyclic PSt’s with two initiator units will over-
lap to obscure their original peak tops; however, one of
them could be due to PSt-monocycle with a potassium salt.
Unfortunately, despite many efforts, the high molecular
weight species could not be desorbed testing nearly 20
available MALDI-matrices.
TABLE 1 Summary for the Synthesis of Macrocyclic Polystyrenes 3a and Their Characterizations by GPC Equipped with RI, UV, IV,
and LS Detectors, Quadruple-detector GPC
Characterization by Quadruple-Detector GPC
Synthesis
RI
UV
IV
LS
Entry [M]/[I]b Yield (%) Mw (Mw/Mn)c
Mp
Mw (Mw/Mn)c Mp
Mw (Mw/Mn)c
Mp
36,900
Mw (Mw/Mn)c
Mp
44,700
d
d
d
d
1
2
3
a
50
200
46.3
45.7
43.4
41,400 (2.62)
49,000 29,700 (2.52)
38,500
30,700 (3.01)
37,400 (2.49)
130,000 (3.45) 126,000 63,500 (3.01)
76,500 117,000 (1.95)
96,300 120,000 (2.58) 127,000
1,000
238,000 (3.16) 222,000 97,500 (3.24) 112,000 202,000 (3.64) 176,000 216,000 (1.97) 219,000
c
Prepared through the polymerizations of styrene (St) with cyclic
initiator 2 in 1,1,1,3,3,3-hexafluoro-2-phenyl-2-propanol (HFPP) at 125 ꢂC
Weight-average molecular weight (molecular weight distribution)
determined by GPC in THF using polystyrene standards.
Molecular weight at the peak top determined by GPC in THF using
d
for 6 h.
b
Monomer/initiator ratio in the feed.
polystyrene standards.
CYCLIC ALKOXYAMINE ENABLING RING-EXPANSION VINYL POLYMERIZATION, NARUMI ET AL.
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JOURNAL OF POLYMER SCIENCE: PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
tive Mps were 44,700, 127,000, and 219,000 g molꢀ1. The
shift to increasing molecular weight with higher [M]/[I] ratio
can be detected, indicative of a living character of the poly-
merization, however, obscured by the radical crossover-reac-
tion. We state that the present analysis would reach the limit
of currently achievable polymer analytics to characterize the
products of this study.
Ring-Opening of Macrocyclic PSt
To provide further insights into the mechanism by other
approaches, we performed ring-opening reactions for 3 with
the Mp for the main peak of 121,000 g molꢀ1 (determined
by a routine GPC). The ring-opening was demonstrated by
cleaving the inherent benzoate linkages using methanolic
KOH in THF to produce product 8 (Scheme 4). Figure 9(a)
shows the GPC trace of 8 with the Mn and Mw/Mn of 13,400
g molꢀ1 and 2.08. The Mp of 14,000 g molꢀ1 was signifi-
cantly shifted to the lower molecular weight regions as com-
pared to the starting 3, which was relatively close to the cal-
culated value of 10,062 g molꢀ1. A shoulder was observed
for the GPC trace of 8 in the higher molecular weight
SCHEME 4 Ring-opening reactions of 3 by (i) the hydrolysis
using methanolic KOH in THF or (ii) the radical crossover reac-
tion with an excess amount of acyclic alkoxyamine
5 in
1,1,1,3,3,3-hexafluoro-2-phenyl-2-propanol (HFPP), producing
linear polystyrene 8 or 9.
Characterization of the Macrocyclic Polystyrenes by the
Quadruple-Detector GPC
Figure 8 shows the GPC traces of 3 obtained by the polymer-
izations of St with 2 using the [M]/[I] ratios of 50:1, 200:1,
and 1000:1, which were detected by the refractive index
(RI), ultraviolet-visible (UV) intrinsic viscosity (IV), and low-
angle light scattering (LALS) as well as right-angle light scat-
tering (RALS) detectors. The differences were that the
shoulders in the low molecular weight regions, which were
observed with the RI and UV, were almost undetected by the
IV and LS; however, these are not unusual results. However,
the UV-trace plausibly as the most molecular weight-inde-
pendent system clearly shows the shoulder at an elution vol-
ume of about ꢃ15 mL, which should be the monocyclic PSt
being assigned by MALDI-TOF-MS.
Table 1 summarizes the results that include weight-average
molecular weights (Mw) determined by the respective detec-
tors. The Mw determined by the LS would reflect exact mo-
lecular weights for cyclic polymers; thus, we concluded that
the polymerizations of St with 2 using the [M]/[I] ratios of
50:1, 200:1, and 1000:1 produce macrocyclic polystyrene 3
with the Mws of 37,400, 120,000, and 216,000 g molꢀ1 in
the yields of 46.3, 45.7, and 43.4%, respectively. The respec-
FIGURE 9 GPC traces of the products after the ring-opened
reactions by a) the hydrolysis and b) the radical crossover reac-
tion. The upper dashed line is the GPC trace of the macrocyclic
polystyrene 3 before the ring-opened reactions.
3414
INTERSCIENCE.WILEY.COM/JOURNAL/JPOLA

ARTICLE
regions. However, in the 1H NMR spectrum of 8 [Fig. 6(b)],
the signals due to the methylene protons adjacent to the
ester linkage at 5.5-5.3 ppm disappeared. Alternatively, the
signals assignable to methylene protons in the neighborhood
of a hydroxyl group were observed at 4.7–4.5 ppm. The
MALDI-TOF MS spectrum of 8 showed a series of the peaks
with the m/z values assignable to ring-opened species
[Fig. 7(b)]. As an example, the m/z of 4231.3 corresponds
to the [M þ 2Na - H]þ of 35-mer PSt with bearing a
triazole ring and chain-ends of a hydroxyl and a carboxylic
acid groups, which agrees with the calculated value for
generating macrocyclic PSt’s. The occurrence of the radical
ring-crossover reactions was experimentally proven, whereas
the polymerization-products contain linear or catenane-like
species. Thus, ongoing research is directed to the polymer-
ization of macromonomers to prepare grafted polymeric
cycles. The polymerization mechanisms with cyclic NMP-
initiator can then be further supported by microscopy data.
The authors A.N. and W.H.B. thank to the program ‘‘Accelera-
tion for Internationalization of Education in University’’ sup-
ported by the Ministry of Education, Culture, Sports, Science
and Technology, Japan. The authors also thank the DFG for
the grants DFG INST 271/249/1, INST 271/247/1; INST
271/248-1 and BI 1337/6-1.
C312H316N4O4Na2 of 4231.9. Thus, the hydrolysis reaction
obviously proceeded and the main species after the hydroly-
sis was assignable to the ring-opened PSt 8 as illustrated in
Scheme 4. The results to be emphasized here should be that
the molecular weight of the product drastically decreased
after the hydrolysis as stated above, indicating that macrocy-
clic PSt 3 contained multiple benzoate linkages in the main
chain. This supports the proposed mechanisms.
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