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filtered, and the solvent was removed in vacuo. The material was
purified by column chromatography (1:1 EtOAc:cyclohexane) to give
activated monomer 11 (0.32 g, 61%) as a clear oil. 1H NMR (CDCl3):
δ 7.41 (d, J = 8.6, 2H), 7.21−7.15 (m, 2H), 4.71 (s, 2H), 4.48−4.41
(m, 2H, rotamers), 3.90−3.74 (m, 2H, rotamers), 3.26 and 3.16 (s,
1.3:1, 3H, rotamers), 1.69 (br, s, 1H). 13C NMR (CDCl3): δ 153.4,
150.3, and 150.1 (rotamers), 150.0 and 149.1 (rotamers), 139.1 and
139.0 (rotamers), 128.0 and 127.9 (rotamers), 120.84 and 120.81
(rotamers), 65.4 and 65.3 (rotamers), 64.2, 51.2, and 49.8 (rotamers)
39.6 and 37.6 (rotamers). HRMS: calcd [M]+ (C12H14ClNO5):
287.0561. Found: (CI) 287.0570.
(s, 1H). 13C NMR (CDCl3): δ 171.0, 155.1, 150.8, 150.6, 145.6, 133.6,
129.8, 125.4, 121.7, 120.9, 68.2, 61.6, 33.8. HRMS: calcd [M + H]+
(C17H16NO8S): 394.0597. Found: (CI) 394.0595.
Synthesis of Polymer 3. Monomer 16 (0.100 g, 0.25 mmol, 20
equiv), end-cap 1742 (0.0024 g, 0.013 mmol, 1.0 equiv), DIPEA (0.01
mL, 0.063 mmol, 5.0 equiv), and DMAP (0.0002 g, 0.0013 mmol, 0.1
equiv) were stirred in minimal anhydrous toluene (0.3 mL) at −15 °C
for 8 h. The reaction was allowed to warm up to room temperature
and stirred for another 15 h. The reaction mixture was then diluted
with 0.5 mL of DMF and dialyzed overnight in DMF. The membrane
content was then diluted with an equal volume of H2O and lyophilized
1
Synthesis of Polymer 2. Monomer 11 (0.25 g, 0.87 mmol, 20
equiv), end-cap 8 (0.014 g, 0.044 mmol, 1.0 equiv), DIPEA (0.038
mL, 0.22 mmol, 5.0 equiv), and DMAP (0.0005 g, 0.0044 mmol, 0.1
equiv) were stirred in minimal anhydrous toluene (1 mL) at 90 °C for
6 h. The reaction was allowed to cool down to room temperature.
Dilution with CH2Cl2, washing with 1 M HCl and then 1 M Na2CO3,
then drying the organic layer with MgSO4, filtering, and evaporating
typically provided yields of 85−90% of polymeric/oligomeric material.
However, to remove the small molecule byproducts as well as
fractionate the higher MW polymers from the lower MW oligomers,
the reaction mixture was instead diluted with 0.5 mL of DMF and then
dialyzed overnight against DMF. The fraction contained in the
membrane was then diluted with an equal volume of H2O and
to give polymer 3 (0.035 g, 51%). H NMR spectroscopy indicated a
degree of polymerization of ∼15 by integrating methylene peaks
against the dithiopyridyl end-cap. 1H NMR (CDCl3): δ 8.49−8.43 (m,
1H), 8.24−8.18 (m, 2H), 8.08−8.04 (m, 1H), 7.51−7.31 (br, m,
30H), 7.23−7.16 (br, m, 30H), 5.30−5.20 (m, 30H), 4.47−4.39 (br,
m, 30H), 3.27−3.19 (br, m, 30H). SEC: Mn = 5040, PDI = 1.67.
Synthesis of Compound 20. Activated carbonate 5 (0.70 g, 2.2
mmol, 1.0 equiv), phenol 1943 (0.33 g, 2.4 mmol, 1.1 equiv), DIPEA
(0.30 μL, 2.9 mmol, 1.6 equiv), and DMAP (0.03 g, 0.24 mmol, 0.1
equiv) were dissolved in 30 mL of anhydrous CH2Cl2 and stirred at
room temperature for 15 h. The reaction was then washed with 1 M
HCl followed by brine. The organic layer was dried over MgSO4 and
filtered, and the solvent was removed in vacuo. The material was
purified by column chromatography (1:4 EtOAc:cyclohexane) to give
1
lyophilized to give polymer 2 (0.085 g, 36%). H NMR spectroscopy
1
indicated a degree of polymerization of ∼20 by integrating methylene
20 (0.58 g, 82%) as a clear oil. H NMR (CDCl3): δ 7.32 (d, J = 8.2,
1
peaks against the Boc end-cap. H NMR (CDCl3): δ 7.45−7.31 (m,
2H), 7.15 (d, J = 8.2, 2H), 4.42 (s, 2H), 4.36−4.30 (m, 2H), 3.57−
3.51 (m, 2H), 3.36 (s, 3H), 2.93 (s, 3H), 1.45 (s, 9H). 13C NMR
(CDCl3): δ 155.6, 153.4, 150.3, 136.0, 128.6, 120.8, 79.8, 73.8, 66.4,
58.0, 47.6, and 47.3 (rotamers), 35.4 and 35.0 (rotamers), 28.2.
HRMS: calcd [M]+ (C17H25NO6): 339.1682. Found: (EI) 339.1677.
Synthesis of Compound 23. Alcohol 1742 (0.24 g, 1.2 mmol, 1.0
equiv), carbonate 2234 (0.62 g, 1.5 mmol, 1.2 equiv), DIPEA (0.35
mL, 1.9 mmol, 1.5 equiv), and DMAP (0.015 g, 0.12 mmol, 0.1 equiv)
were dissolved in 20 mL of anhydrous CH2Cl2 and stirred at 35 °C
until reaction was complete (∼4 h) as determined by TLC. The
reaction was then washed with 1 M HCl followed by brine. The
organic layer was dried over MgSO4 and filtered, and the solvent was
removed in vacuo. The material was purified by column chromatog-
raphy (1:3 EtOAc:cyclohexane) to give 23 (0.40 g, 69%) as a white
41H), 7.24−7.04 (m, 45H), 5.19−5.06 and 4.72−4.63 (m, 26 and
15H, respectively, rotamers), 4.51−4.28 (m, 42H), 3.85−3.51 (m,
43H), 3.30−2.86 (m, 66H), 1.47 (s, 9H, Boc). SEC: Mn = 3200 g/mol,
PDI = 1.26.
Synthesis of Compound 13. TBS protected mercaptoethanol41
(2.0 g, 10.4 mmol, 1.0 equiv) and pyridine (1.2 mL, 16.0 mmol, 1.5
equiv) were dissolved in 50 mL of anhydrous CH2Cl2 and stirred at 0
°C. Triphosgene (1.04 g, 3.45 mmol, 0.4 equiv) was slowly added to
the reaction, which was stirred at 0 °C for 1 h and then 3 h at room
temperature. The reaction mixture was then washed three times with 1
M HCl followed by water and then brine. The organic layer was dried
over MgSO4, filtered, and the solvent was removed in vacuo.
Compound 13 was then used in the next step without further
purification (2.12 g, 80%). 1H NMR (CDCl3): δ 3.83 (t, J = 6.4, 2H),
3.11 (t, J = 6.4, 2H), 0.90 (s, 9H), 0.08 (s, 6H).
1
solid. H NMR (CDCl3): δ 8.52−8.47 (m, 1H), 7.73−7.62 (m, 2H),
7.34 (d, J = 8.6, 2H), 7.16−7.09 (m, 3H), 4.73 (s, 2H), 4.51 (t, J = 6.6,
2H), 3.15 (t, J = 6.6, 2H), 0.95 (s, 9H), 0.11 (s, 6H). 13C NMR
(CDCl3): δ 159.3, 153.3, 149.74, 149.67, 139.3, 136.9, 126.9, 120.8,
120.5, 119.9, 65.9, 64.2, 36.9, 25.8, 18.3, −5.4. HRMS: calcd [M]+
(C21H29NO4S2Si): 451.1307. Found: (EI) 451.1307.
Synthesis of Compound 15. Thiochloroformate 13 (1.0 g, 4.0
mmol, 1.0 equiv), 4-nitrophenyl-activated 4-hydroxybenzyl alcohol
1428 (1.15 g, 4.0 mmol, 1.0 equiv), pyridine (1.8 mL, 24.0 mmol, 6.0
equiv), and DIPEA (1.0 mL, 8.0 mmol, 2.0 equiv) were dissolved in 75
mL of anhydrous THF and stirred at 50 °C for 6 h. Another equivalent
of thiochloroformate 13 (1.0 g, 4.0 mmol, 1.0 equiv) was added, and
the reaction was stirred at 45 °C for 15 h. The reaction was then
diluted with 200 mL of CH2Cl2 and washed with 1 M HCl followed by
brine. The organic layer was dried over MgSO4 and filtered, and the
solvent was removed in vacuo. The material was purified by column
chromatography (1:6 EtOAc:cyclohexane) to give 15 (2.0 g, 65%) as a
Synthesis of Compound 24. Compound 23 (0.40 g, 0.89 mmol, 1.0
equiv) was stirred at room temperature in 10 mL of 1% HCl in ethanol
until the reaction was complete (∼1.5 h) as determined by TLC. The
reaction was neutralized with minimal 1 M NaHCO3 as determined
with pH paper. The reaction was then diluted with 30 mL of CH2Cl2
and washed with water followed by brine. The organic layer was dried
over MgSO4 and filtered, and the solvent was removed in vacuo. The
material was purified by column chromatography (1:3 EtOAc:cyclo-
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white solid. H NMR (CDCl3): δ 8.35−8.31 (m, 2H), 7.52−7.42 (m,
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4H), 7.31−7.28 (m, 2H), 5.25 (s, 2H), 3.80 (t, J = 6.4, 2H), 3.04 (t, J
= 6.4, 2H), 0.90 (s, 9H), 0.07 (s, 6H). 13C NMR (CDCl3): δ 171.1,
155.2, 150.8, 150.6, 145.6, 133.9, 129.8, 125.4, 121.7, 120.9, 67.9, 62.0,
33.8, 25.8, 18.3, −5.4. HRMS: calcd [M + H]+ (C23H30NO8SSi):
508.1461. Found: (CI) 508.1449.
hexane) to give 24 (0.24 g, 80%) as a clear oil. H NMR (CDCl3): δ
8.45 (d, J = 4.7, 1H), 7.71−7.67 (m, 1H), 7.64 (dt, J = 7.1, 1.2, 1H),
7.36 (d, J = 8.8, 2H), 7.14 (d, J = 8.8, 2H), 7.11−7.08 (m, 1H), 4.66 (s,
2H), 4.49 (t, J = 6.4, 2H), 3.13 (t, J = 6.4, 2H), 2.44 (br, 1H). 13C
NMR (CDCl3): δ 159.3, 153.3, 150.2, 149.7, 138.9, 137.1, 128.0,
120.94, 120.90, 119.9, 66.0, 64.4, 36.9. HRMS: calcd [M]+
(C15H15NO4S2): 337.0442. Found: (EI) 337.0438.
Synthesis of Monomer 16. Compound 15 (0.50 g, 0.98 mmol, 1.0
equiv) was stirred at room temperature in 10 mL of 1% HCl in ethanol
until the reaction was complete (∼1.5 h) as determined by TLC. The
reaction was neutralized with minimal 1 M NaHCO3 as determined
with pH paper. The reaction was then diluted with 30 mL of CH2Cl2
and washed with water followed by brine. The organic layer was dried
over MgSO4 and filtered, and the solvent was removed in vacuo. The
material was purified by column chromatography (1:19
EtOAc:CH2Cl2) to give monomer 16 (0.31 g, 80%) as a clear oil.
1H NMR (CDCl3): δ 8.35−8.31 (m, 2H), 7.53−7.44 (m, 4H), 7.33−
7.30 (m, 2H), 5.28 (s, 2H), 3.85 (br, m, 2H), 3.10 (t, J = 6.0, 2H), 2.19
Monomer Cyclization Kinetics Studies. Compound 1834 by
UV−vis Spectroscopy. 3 mL of preheated isopropanol was added to a
quartz cuvette containing compound 18 (1.50 mg), and the resulting
mixture was incubated at 37 °C over a period of 8 days. Absorbance
measurements at 282 nm were made at regular intervals throughout
the cyclization process with the initial time point (t = 0) defined at the
time of isopropanol addition. As the cyclization did not reach
completion over this time period, the relative concentrations of
compound 18 and 4-hydroxybenzyl alcohol throughout the cyclization
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dx.doi.org/10.1021/ma301667c | Macromolecules 2012, 45, 7364−7374