4-(4-(1-Hydroxyethyl)-2-methoxy-5-nitrophenoxy)butanoic acid
(HEMNPBA). The product was prepared based on the synthetic
protocols by Holmes.30,45 Acetovanillone was suspended together
with 1.1 equivalents of methyl 4-bromobutyrate and 1.5 equiva-
lents of potassium carbonate in anhydrous dimethylformamide
and stirred under argon for 16 h. Afterwards, the reaction mixture
was diluted with an excess amount of water to dissolve all inor-
ganic salts and then extracted with ethyl acetate. Removal of the
organic solvent after drying with MgSO4 yielded the -ester product
in quantitative crude yield. Subsequent nitration was achieved by
stirring a 3.7% (w/v) solution of the -ester in a mixture of acetic
anhydride and nitric acid (1 : 2, v/v) at 0 ꢁC for 3 h. The mixture
was precipitated in ice water, filtered and the obtained solid
recrystallized from MeOH/H2O yielding 53% of the nitrated
product. In the next step, the reduction of the group with excess
borohydride was conducted at room temperature for 16 h in
MeOH/THF and directly followed by inducing the ester cleavage
by addition of NaOH in water and stirring the mixture at room
temperature for 7 h. The organic solvents were removed under
reduced pressure and the resulting water phase was slowly acidi-
fied with diluted hydrochloric acid. The crude product was
obtained by extracting the water phase with ethyl acetate and
evaporation of the dried organic layers. Recrystallization from
ethyl acetate/hexane afforded the photolabile molecule
HEMNPBA in 86% yield as a pale yellow solid, mp 165–169 ꢁC;
elemental analysis calc. for C13H19NO6: C, 54.73; H, 6.71; N, 4.91;
147.19, 136.79, 135.79, 133.27, 131.96, 128.99, 126.27, 124.60,
67.77, 66.12, 65.82, 62.17, 18.24. MS (FD) m/z 493.9 (M+).
2,20-(2-Nitro-1,4-phenylene)bis(methylene)bis(oxy)bis(oxo-
methylene)bis(azane-diyl)bis(ethane-2,1-diyl) bis(2-methyl-
acrylate) (CL-2A). 2NPDM (1.00 g, 5.5 mmol) was dissolved in
anhydrous THF (10 mL) and added dropwise to a solution of
2-isocyanatoethyl methacrylate (1.71 g, 11.0 mmol) in anhydrous
THF (15 mL) under nitrogen. The reaction mixture was heated to
ꢁ
65 C and stirred for 24 h at this temperature. FT-IR measure-
ments showed complete disappearance of the corresponding
isocyanato absorption band at 2260 cmꢀ1, thus indicating
complete conversion of the latter. The solvent was evaporated
and the residue was purified by column chromatography over
silica using CHCl3/MeOH (10 : 1) as eluent yielding 72% of CL-
2A (1.95 g, 4.0ꢁmmol) as a slightly yellow colored oil which slowly
solidified at 5 C. Elemental analysis calc. for C22H27N3O10: C,
1
53.55; H, 5.51; N, 8.52.Found: C, 53.75; H, 5.77; N, 8.47%; H
NMR (CDCl3): d ¼ 8.06 (s, 1H), 7.58 (s, 1H), 7.56 (s, 1H), 6.11
(m, 2H), 5.58 (m, 2H), 5.49 (s, 2H), 5.18 (m, 4H), 4.24 (t, 4H, J ¼
5.4 Hz), 3.51 (q, 4H, J ¼ 5.5 Hz), 1.93 (s, 6H).13C NMR (CDCl3):
d ¼ 167.30, 155.80, 147.47, 137.94, 135.91, 132.83, 132.67, 129.16,
126.16, 124.14, 65.00, 63.55, 63.28, 40.44, 18.29. MS (FD) m/z
494.6 (M+).
Bis(2-(methacryloyloxy)ethyl)
0-(2-nitro-1,4-phenylene)bis-
1
found: C, 54.73; H, 7.01; N, 4.79%; H NMR (CDCl3): d ¼ 7.55
(methylene) disuccinate (CL-3A). Mono-2-(methacryloylox-
y)ethyl succinate (2.53 g, 11.0 mmol) was dissolved in anhydrous
benzene and oxalyl chloride (2.79 g, 2 mmol) was added under
nitrogen at room temperature. The reaction mixture was slowly
heated to 85 ꢁC and refluxed for 3 h. After cooling to room
temperature, benzene and excess oxalyl chloride were removed
under reduced pressure. The so obtained acyl chloride was dis-
solved in anhydrous THF (35 mL) and a solution of 2NPDM
(1.00 g, 5.5 mmol) and triethylamine (1.21 g, 12.0 mmol) in THF
(15 mL) was added dropwise. After stirring the mixture overnight
at room temperature, precipitated solids were removed by
filtration and the solution was reduced to dryness. The residue
was dissolved in dichloromethane (100 mL), washed three times
with water, dried with MgSO4 and evaporated. The resulting red
oil was purified by column chromatography over silica using
CHCl3/MeOH (40 : 1) as eluent and afforded 40% of pure CL-
3A (1.34 g, 2.2 mmol). Elemental analysis calc. for C28H33NO14:
C, 55.35; H, 5.47; N, 2.31, found: C, 55.24; H, 5.54; N, 2.38%. 1H
NMR (CDCl3): d ¼ 8.02 (s, 1H), 7.56 (s, 1H), 7.55 (s, 1H), 6.05
(m, 2H), 5.52 (m, 2H), 5.46 (s, 2H), 5.13 (s, 2H), 4.28 (m, 8H),
2.65 (m, 8H), 1.87 (s, 1H). 13C NMR (CDCl3): d ¼ 171.80, 167.06,
147.49, 137.34, 135.89, 132.94, 131.84, 129.32, 126.07, 124.31,
64.67, 63.02, 62.49, 62.26, 28.85, 18.23. MS (FD) m/z 606.8 (M+).
(s, 1H), 7.29 (s, 1H), 5.55 (q, 1H, J ¼ 6.3 Hz), 4.10 (t, 2H, J ¼ 6.1
Hz), 3.97 (s, 3H), 3.73 (t, 2H, J ¼ 6.2 Hz), 1.98 (m, 2H), 1.77
(m, 2H), 1.55 (d, 3H, J ¼ 6.3 Hz). 13C NMR (CDCl3): d ¼ 153.67,
146.38, 138.87, 137.94, 108.62, 108.30, 68.91, 64.65, 61.40, 55.96,
28.89, 25.23, 24.60. MS (FD) m/z 285.0 (M+).
Synthesis of photodegradable crosslinkers
Based on the two different photolabile molecules, four different
crosslinkers were synthesized. The structures of CL-1A, CL-2A,
CL-3A and CL-4B are presented in Scheme 1.
2,20-(2-Nitro-1,4-phenylene)bis(methylene)bis(oxy)bis(oxomethylene)-
bis(oxy)bis-(ethane-2,1-diyl)bis(2-methylacrylate) (CL-1A).
A
solution of hydroxyethylmethacrylate (HEMA) (1.86 g, 14.3
mmol) in anhydrous THF (5 mL) was added dropwise to
a solution of carbonyldiimidazole (CDI) (2.39 g, 14.3 mmol) in
anhydrous THF (20 mL). After stirring the reaction mixture
overnight at room temperature, a solution of 2NPDM (1.31 g,
7.15 mmol) in anhydrous THF (20 mL) together with a 1.75 mol
Lꢀ1 sodium ethanolate suspension (0.2 mL, 0.35 mmol) was
added. Additional stirring for 5 d at room temperature was fol-
lowed by filtration and reduction of the filtrate to dryness under
reduced pressure. The residue was purified by column chroma-
tography over silica using CHCl3/MeOH (20 : 1) as eluent and
yielded CL-1A (1.84 g, 3.72 mmol) as a slightly yellow colored
oil. Yield 52%; elemental analysis calc. for C22H25NO12: C,
2-((1-(4-(4-(2-(Methacryloyloxy)ethylcarbamoyloxy)butoxy)-
5-methoxy-2-nitro-phenyl)ethoxy)carbonylamino)ethyl methac-
rylate (CL-4B). 2-Isocyanatoethyl methacrylate (1.14 g, 7.4 mmol)
was dissolved in anhydrous THF (5 mL) and added to a solution of
HEMNPBA (1.00 g, 3.5 mmol) and dibutyltin dilaurate (0.11 g,
0.18 mmol) in anhydrous THF (25 mL) under nitrogen. After the
1
53.33; H, 5.09; N, 2.83%; found: C, 53.53; H, 5.07; N, 2.81.) H
ꢁ
NMR (CDCl3): d ¼ 8.17 (s, 1H), 7.68 (s, 1H), 7.67 (s, 1H), 6.12
(d, 1H, J ¼ 5.2 Hz), 5.59 (m, 4H), 5.23 (s, 2H), 4.41 (m, 8H) ppm,
1.93 (d, 6H, J ¼ 3.6 Hz). 13C NMR (CDCl3): d ¼ 167.05, 154.60,
mixture was heated to 65 C and stirred for 48 h at this tempera-
ture, FT-IR measurements showed complete disappearance of the
corresponding isocyanato absorption band at 2260 cmꢀ1. This
1428 | Soft Matter, 2011, 7, 1426–1440
This journal is ª The Royal Society of Chemistry 2011