Ferreira et al.
(
34 mg, 0.2 mmol) and the resulting slurry stirred for 1 h at
room temperature under inert atmosphere. PEG mesylate
12a , M ) 6 kDa, 0.63 g, 0.1 mmol) was then added and
TEMPO - methylenes), 1.10 (s, 12 H, axial TEMPO - methyls),
1.07 (s, 12 H, equatorial TEMPO - methyls). 13C NMR (CDCl
)
3
(
w
δ: 155-110 (several signals, resulting from the reduction in
stirring resumed for 48 h at room temperature. The suspension
was then filtered and the filtrate concentrated under reduced
pressure. This solution was then added to diethyl ether (100
mL) that was stirred vigorously and the precipitate collected
by filtration, washed twice with diethyl ether (2 × 50 mL),
and dried under vacuum. The product 5 was obtained as pale
orange solid (0.56 g, 89% based on polymer recovery). T )
5
resulting from the reduction in situ of the nitroxyl radicals
situ of the nitroxyl radicals with phenylhydrazine), 71.5
-
1
(broad), 66.4, 60.3, 44.7, 29.1, 21.6. FTIR (cm ): 2884, 1467,
+
1343, 1281, 1242, 1148, 1113. MALDI-TOF MS M
w
[6 + K ]:
calcd 10365 Da, found 10374 Da. Calculated nitroxyl loading:
-
1
0.19 mmol‚g
.
Gen er a l P r oced u r e for th e P r ep a r a tion of th e P EG-
Su p p or ted Meth yl Isop h th a la te Ester s 16 a n d 17. To a
g
1
6
8.7 °C. H NMR (DMSO-d ) δ: 7.36-6.55 (several signals,
suspension of the bis-mesylate (12a , M
w
) 6 kDa, 2.46 g, 0.4
mmol) and K CO (0.44 g, 3.2 mmol) in acetone (100 mL) was
2
3
with phenylhydrazine), 3.72 (m, 4H, PEG - R-methylenes),
3
-
added the phenol 15 (0.67 g, 3.2 mmol), and the mixture was
maintained under reflux for 12 h. Upon filtration of the solids
and solvent evaporation, the remaining material was dissolved
.61-3.09 (bm, PEG - methylenes), 1.89-1.82 (m, 4H, TEMPO
methylenes), 1.31-1.19 (m, 4H, TEMPO - methylenes), 1.08
(
s, 12 H, TEMPO - axial methyls), 1.05 (s, 12 H, TEMPO -
2 2
in CH Cl (5 mL), the solution was added dropwise to diethyl
1
3
equatorial methyls). C NMR (CDCl ) δ: 155-110 (several
signals, resulting from the reduction in situ of the nitroxyl
radicals with phenylhydrazine), 70.6 (broad), 68.3, 61.7, 44.7,
2
1
6
3
ether (500 mL) that was stirred vigorously, and the resulting
suspension was stirred for 30 min. The precipitate was filtered
and washed with diethyl ether (2 × 50 mL) to afford the
tetraester 17 as a white solid (2.50 g, 97% based on polymer
9.7, 21.0. FTIR (cm-1): 2883, 1467, 1344, 1280, 1242, 1149,
+
114. MALDI-TOF MS M
w
[5 + K ]: calcd 6822 Da, found
1
recovery). H NMR (CDCl
methyne), 7.76 (d, 4H, J ) 1.42 Hz, aryl - methynes), 4.20
(m, 4H, PEG - R-methylenes), 3.92 (s, 12H, Ar-CO-OCH ), 3.87
(m, 8H, PEG - methylenes), 3.79-3.25 (bm, PEG - methylenes).
3
) δ: 8.26 (t, 2H, J ) 1.42 Hz, aryl
-
1
817 Da. Calculated nitroxyl loading: 0.29 mmol‚g
.
-
Eth er 2. Isolated by column chromatography as a red oil
3
1
(63 mg, 65% based on recovery). H NMR (DMSO-d
6
) δ: 7.39-
1
3
6
.52 (several signals, resulting from the reduction in situ of
C NMR (CDCl
3
) δ: 166.7, 156.6, 131.7, 122.7, 121.1, 70.7
-
1
the nitroxyl radicals with phenylhydrazine), 3.64-3.41 (bm,
1
TEMPO - methyne), 3.24 (s, 3H, triethylene glycol monomethyl
(broad), 52.7. FTIR (cm ) 2879, 1726, 1351, 1292, 1112.
MALDI-TOF MS M [17 + K ]: calcd 6896 Da, found 6879
+
2H, triethylene glycol monomethyl ether - methylenes, m, 1H,
w
Da.
ether - methyl) 1.90-1.83 (m, 2H, TEMPO - methylenes),
Bis-ester 16. Isolated as a white solid (1.93 g, 93% based
on polymer recovery). 1H NMR (CDCl ) δ: 8.27 (t, 1H, J )
1
.29-1.19 (m, 2H, TEMPO - methylenes), 1.08 (s, 6 H, axial
3
TEMPO - methyls), 1.05 (s, 6 H, equatorial TEMPO - methyls).
1.42 Hz, aryl - methyne), 7.76 (d, 2H, J ) 1.42 Hz, aryl -
1
3
C NMR (DMSO-d
6
) δ: 155-110 (several signals, resulting
methynes), 4.19 (m, 2H, PEG - R-methylenes), 3.91 (s, 6H, Ar-
from the reduction in situ of the nitroxyl radicals with
phenylhydrazine), 71.7, 70.7, 70.6, 70.3, 70.2, 70.0, 67.2, 58.4,
5
1
CO-OCH ), 3.79-3.25 (bm, PEG - methylenes) 3.35 (s, 3H,
3
PEG - methyl). 13C NMR (CDCl ) δ: 166.8, 156.6, 131.6, 122.7,
3
-
1
-1
8.3, 45.0, 32.9, 20.8. FTIR (cm ) 2887, 1467, 1344, 1278,
246, 1149, 1113. MALDI-TOF MS (+20 kV, Reflectron) M [2
120.8, 72.0, 70.5 (broad), 58.9, 52.6. FTIR (cm ): 2881, 1727,
1347, 1289, 1114. MALDI-TOF MS Mw [16 + K ]: calcd 5214
+
+
+
K ]: calcd 357.19 Da, found 375.00 Da. Calculated nitroxyl
Da, found 5203 Da.
-
1
loading: 2.67 mmol‚g
.
Gen er a l P r oced u r e for th e P r ep a r a tion of th e P EG-
su p p or ted Isop h th a lic Acid s 18 a n d 19. A solution of the
tetraester 17 (1.00 g, 0.16 mmol) in 2 M KOH (25 mL) was
stirred at room temperature for 18 h. HCl (5% aq) was then
added until pH 2, after which time the aqueous layer was
Eth er 3. Isolated as a pale orange solid (0.19 g, 85% based
1
on polymer recovery). T
7
g
) 51.3 °C. H NMR (DMSO-d ) δ:
6
.35-6.61 (several signals, resulting from the reduction in situ
of the nitroxyl radicals with phenylhydrazine), 3.74 (m, 4H,
PEG - R-methylenes), 3.69-3.12 (bm, PEG - methylenes), 3.32
extracted with CH Cl2 (5 × 25 mL). The combined organic
2
(
1
s, 3H, PEG - methyl)1.91-1.82 (m, 4H, TEMPO - methylenes),
extracts were dried over MgSO , filtered, and concentrated
4
.31-1.16 (m, 4H, TEMPO - methylenes), 1.07 (s, 12 H, axial
under vacuum to a small volume (∼5 mL). This solution was
added dropwise to diethyl ether (250 mL), and the resulting
suspension was stirred for 30 min. The precipitate was filtered
and washed with diethyl ether (2 × 50 mL) to afford the
tetraacid 19 as a white solid (0.90 g, 95% based on polymer
TEMPO - methyls), 1.03 (s, 12 H, equatorial TEMPO -
1
3
methyls). C NMR (CDCl ) δ: 155-110 (several signals,
resulting from the reduction in situ of the nitroxyl radicals
with phenylhydrazine) 70.6 (broad), 67.9, 61.4, 45.0, 29.1, 20.9.
3
-
1
1
FTIR (cm ): 2883, 1467, 1344, 1280, 1242, 1148, 1114.
recovery). H NMR (CDCl ) δ: 8.25 (bs, 2H, J ) 1.42 Hz, aryl
3
+
MALDI-TOF MS M
Calculated nitroxyl loading: 0.86 mmol‚g
Eth er 4. Isolated as a pale orange solid (0.49 g, 96% based
on polymer recovery). T
7
w
[3 + K ]: calcd 2314 Da, found 2313 Da.
- methyne), 7.72 (bs, 4H, J ) 1.42 Hz, aryl - methynes), 4.16
(m, 4H, PEG - R-methylenes), 3.84 (m, 4H, PEG - â-methyl-
enes), 3.58 (bm, PEG - methylenes). FTIR (cm ): 2886, 1704,
1607, 1445, 1343, 1279, 1113. MALDI-TOF MS M [19 + K ]:
calcd 6836 Da, found 6822 Da.
-
1
.
-
1
1
+
g
) 59.99 °C. H NMR (DMSO-d
6
) δ:
w
.34-6.58 (several signals, resulting from the reduction in situ
of the nitroxyl radicals with phenylhydrazine), 3.75 (m, 4H,
18. Isolated as a white solid (0.76 g, 92% based on polymer
1
PEG - R-methylenes), 3.68-3.15 (bm, PEG - methylenes),
3
recovery). H NMR (CDCl ) δ: 8.25 (bs, 1H, aryl - methyne),
1
.89-1.79 (m, 2H, TEMPO - methylenes), 1.33-1.17 (m, 2H,
7.71 (bs, 2H, aryl - methynes), 4.14 (m, 2H, PEG - R-methyl-
TEMPO - methylenes), 1.08 (s, 6 H, axial TEMPO - methyls),
1
enes), 3.62 (bm, PEG - methylenes), 3.39 (m, 3H, PEG -
.03 (s, 6 H, equatorial TEMPO - methyls). 13C NMR (CDCl
)
-1
3
methyl). FTIR (cm ): 2883, 1703, 1601, 1440, 1350, 1283,
+
δ: 155-110 (several signals, resulting from the reduction in
1110. MALDI-TOF MS M
5163 Da.
w
[18 + Na ]: calcd 5168 Da, found
situ of the nitroxyl radicals with phenylhydrazine), 72.0, 70.6
-
1
(
broad), 68.7, 61.7, 59.1, 44.8, 29.0, 21.5. FTIR (cm ): 2885,
Gen er a l P r oced u r e for th e P r ep a r a tion of th e Br a n ch -
ed Nitr oxyl Ca ta lysts 7 a n d 8. A solution of tetraacid 19
100 mg, 0.016 mmol), thionyl chloride (0.5 mL, 0.65 mmol),
and DMF (1 drop) in THF (10 mL) was maintained under
reflux for 4 h. The solvent was removed in vacuo. The solid
1
M
467, 1360, 1344, 1280, 1242, 1149, 1109. MALDI-TOF MS
+
w
[4 + K ]: calcd 5176 Da, found 5169 Da. Calculated
1
(
-
nitroxyl loading: 0.19 mmol‚g
.
Eth er 6. Isolated as a pale orange solid (1.01 g, 97% based
1
on polymer recovery). T
7
g
) 53.6 °C. H NMR (DMSO-d
6
) δ:
was then dissolved in CH
solution of 4-hydroxy-TEMPO (689 mg, 4 mmol) and pyridine
(800 µL, 10 mmol) in CH Cl (10 mL) and the resulting solution
2 2
Cl (5 mL) and added dropwise to a
.34-6.58 (several signals, resulting from the reduction in situ
of the nitroxyl radicals with phenylhydrazine), 3.79 (m, 4H,
2
2
PEG - R-methylenes), 3.70-3.21 (bm, PEG - methylenes),
stirred at room-temperature overnight. The solution was then
maintained under reflux for 5 h, after which time the solution
1
.93-1.85 (m, 4H, TEMPO - methylenes), 1.34-1.19 (m, 4H,
6
858 J . Org. Chem., Vol. 69, No. 20, 2004