Soluble Supports Tailored for Organic Synthesis
J. Am. Chem. Soc., Vol. 120, No. 37, 1998 9491
1-Hydroxy-2-phenyl-2-(4-tert-butoxycarbonylamino-2,2,6,6-tet-
ramethyl-1-piperidinyloxy)ethane (17). The ester 16 (0.9 g, 1.8
mmol) was dissolved in a 10 N NaOH/THF/MeOH (3:1:1) mixture
(16 mL) and stirred for 8 h at room temperature. The reaction mixture
was then diluted with diethyl ether (50 mL) and partitioned. The
organic fraction was washed with brine (2 × 50 mL), dried (Na2SO4),
and evaporated in Vacuo. The crude residue was purified by silica gel
chromatography (DCM/MeOH 95:5) to give alcohol 17 as a white solid
(700 mg, 98%). 1H NMR (CDCl3) δ 7.25 (bm, 5H, Ar-H), 5.2 (dd,
1H, CH), 4.35 (bs, 1H), 4.2 (dd, 1H, CH), 3.87 (bs, 1H), 3.75 (dd, 1H,
CH), 1.95-1.85 (complex m, 2H), 1.65 (s, 3H, CH3), 1.60 (s, 9H,
tert-butyl), 1.35-1.00 (complex m, 11H, 3 × CH3 and CH2); 13C NMR
(CDCl3) δ 155.19, 139.92, 128.21, 127.93, 127.67, 83.89, 79.28, 66.62,
60.48, 46.52, 32.97, 28.40, 20.90; HRFABMS calcd for C22H36N2O4
393.3675; obsd 393.3672.
Diazene 3. A solution of alcohol 17 (700 mg, 1.78 mmol), the diacid
18 (180 mg, 0.71 mmol), EDC (544 mg, 2.84 mmol), hydroxybenzo-
triazole (HOBt, 383 mg, 2.84 mmol), and DIPEA (0.74 mL, 4.26 mmol)
in THF (10 mL) was stirred for 8 h at room temperature. The reaction
mixture was then diluted with diethyl ether (50 mL) and washed
sequentially with 1 N HCl (3 × 50 mL), saturated NaHCO3 (3 × 50
mL), and brine (2 × 50 mL). The combined organic fractions were
then combined, dried (Na2SO4), and evaporated in Vacuo to give a crude
colorless oil that was purified by silica gel chromatography (Et2O/
hexane 1:1). This gave initiator 3 as a white crystalline solid (557
mg, 76%). 1H NMR (CDCl3) δ 7.34-7.2 (complex m, 10H, Ar-H),
4.89 (dd, 2H, CH), 4.60 (m, 2H, CH), 4.31-4.24 (complex m, 3H),
3.75 (bs, 1H), 2.39-2.17 (complex m, 8H, 4 × CH2), 1.79 (d, 2H),
1.67 (d, 2H), 1.60 (s, 3H, CH3), 1.58 (s, 3H, CH3), 1.42 (s, 18H, 2 ×
tert-butyl), 1.42 (s, 6H, 2 × CH3), 1.32 (s, 6H, 2 × CH3), 1.30-1.28
(m, 2H), 1.16 (s, 6H, 2 × CH3), 0.65 (s, 6H, 2 × CH3); 13C NMR
(CDCl3) δ 170.84, 155.19, 139.92, 129.02, 127.93, 127.67, 117.41,
83.89, 79.28, 71.76, 66.40, 60.48, 46.52, 41.99, 33.84, 32.97, 30.29,
28.96, 23.81, 23.47, 20.90; HRFABMS calcd for C56H84N8O10Cs
1161.5365; obsd 1161.5437.
1-Methacryloyloxy-2-phenyl-2-(2′,2′,6,6′-tetramethyl-1-piperidi-
nyloxy)ethane (4). 1-Hydroxy-2-phenyl-2-(2′,2′,6′,6′-tetramethyl-1-
piperidinyloxy)ethane (19, 15 g, 54 mmol, 1 equiv) was dissolved in
dry DCM (150 mL). Triethylamine (12.2 mL, 87.5 mmol, 1.6 equiv)
was added followed by methacryloyl chloride (20, 7.9 mL, 82 mmol,
1.5 equiv), and an ice bath was applied briefly. After being stirred
under a nitrogen atmosphere for 2.5 h, the reaction mixture was washed
with 1 N HCl (3 × 100 mL) and brine (100 mL), dried (Na2SO4), and
evaporated to dryness. The crude product was purified by column
chromatography (19:1 hexane:ethyl acetate). This gave 4 as a white
solid (12.1 g, 65%). 1H NMR (400 MHz, CDCl3) δ 7.33-7.22 (m,
5H, Ar-H), 5.98 (s, 1H, CH2), 5.47 (s, 1H, CH2), 4.95 (t, 1H, CH),
4.62 (dd, 1H, CH), 4.33 (dd, 1H, OH), 1.84 (s, 3H, CH3), 1.62, 1.48,
1.37, 1.31, 1.17, 1.03, 0.70 (each br s, 18H, 3 × CH2 and 4 × CH3);
13C NMR (CDCl3) δ 167.14, 140.64, 136.15, 127.93, 127.52, 125.53,
83.83, 66.47, 60.03, 40.37, 33.96, 20.28, 18.26, 17.10; HRFABMS calcd
for C21H31NO3 (M + Na)+ 368.2202; obsd 368.2214.
General Procedure for Block and Graft Copolymer Synthesis.
Monomers were distilled prior to use except for acrylamide and its
derivatives which were used as received. Polymerization yields were
determined gravimetrically and calculated from a theoretical yield based
on 100% monomer conversion. Although often too small and/or broad
to accurately determine, some initiator-derived resonances were
observed by 1H and 13C NMR analysis and are reported in those
instances. The general method for copolymer synthesis is illustrated
once each for formation of the block copolymer polyS-BS and graft
copolymer polyS(4)-DS. For homopolymer synthesis only the first
polymerization at 70 °C occurs. Note that the precipitation solvents
change for each copolymer.
(br s, polymer backbone), 1.65-1.2 (br s, polymer backbone); 13C NMR
(CDCl3) δ 145.27, 127.83, 125.66, 85.38, 73.35, 70.44, 40.47, 34.05,
20.38, 17.16.
Poly(4-tert-butylstyrene) (BS). Reaction: 300 mg of 1 (0.39 mmol,
1 equiv) and 4-tert-butylstyrene (6, 1.42 mL, 7.75 mmol, 20 equiv) in
DCB (3 mL). Precipitation: DCM/methanol to give a white solid, yield
85%. Mn(THF) ) 24 000 and PD ) 2.36; 1H NMR (CDCl3) δ 7.35-
6.8 (br m, Ar-H), 6.8-6.05 (br m, Ar-H), 2.15-1.5 (br m, polymer
backbone), 1.5-1.1 (br s, tert-butyl group and polymer backbone); 13
C
NMR (CDCl3) δ 147.95, 142.72, 127.21, 124.61, 85.33, 40.47, 39.79,
34.23, 31.53, 20.32, 17.16.
Poly(3,4-dimethoxystyrene) (DS). Reaction: 300 mg of 1 (0.39
mmol, 1 equiv) and 3,4-dimethoxystyrene (7, 1.15 mL, 7.75 mmol, 20
equiv) in DCB (3 mL). Precipitation: DCM/methanol to give a white
solid, yield 75%. Mn(THF) ) 19 000 and PD ) 1.67; 1H NMR (CDCl3)
δ 6.75-6.25 (br m, Ar-H), 6.25-5.75 (br m, Ar-H), 3.95-3.4 (br d,
-OCH3), 2.2-1.6 (br s, polymer backbone), 1.6-1.2 (br s, polymer
backbone); 13C NMR (CDCl3) δ 148.34, 147.02, 137.94, 127.71, 127.13,
119.42, 110.49, 85.26, 73.26, 70.33, 55.59, 44.72, 40.13, 33.99, 20.25,
17.07.
Poly(N-vinylpyrrolidinone) (VP). Reaction: 140 mg of 1 (0.18
mmol, 1 equiv) and N-vinylpyrrolidinone (8, 0.39 mL, 3.6 mmol, 20
equiv) in DCB (1.5 mL). Precipitation: methanol/diethyl ether, then
DCM/hexane to give a white powder, yield 74%. Mn(CHCl3) ) 5100
1
and PD ) 1.44; H NMR (CDCl3) δ 4.05-3.5 (br m, 1H, CH), 3.5-
3.05 (br s, 2H, CH2), 2.55-1.3 (br m); 13C NMR (CDCl3) δ 175.45,
127.78, 73.27, 44.81, 43.52, 42.34, 31.39, 19.93, 18.26, 18.00.
Poly(N-isopropylacrylamide) (IA). Reaction: 131 mg of 1 (0.17
mmol, 1 equiv) and N-isopropylacrylamide (9, 388 mg, 3.4 mmol, 20
equiv) in DMF (1.5 mL). Precipitation: THF/diethyl ether to give a
white solid, yield 54%. Mn(CHCl3) ) 18 100 and PD ) 1.40; 1H NMR
(CDCl3) δ 6.8-5.7 (br s, 1H, NH), 4.1-3.9 (br s, 1H, CH), 2.4-1.2
(br m), 1.2-0.95 (br s, 6H, CH3); 13C NMR (CDCl3) δ 174.54, 127.69,
73.09, 70.76, 42.19, 41.24, 35.10, 22.46, 20.83, 17.45.
2. Copolymers. Polystyrene-Poly(4-tert-butylstyrene) (S-BS).
A solution of the homopolymer polyS 102 mg (0.98 mmol of styrene
residues estimated, 1 equiv) in 4-tert-butyl styrene (6, 0.197 mL, 1.08
mmol, 1.1 equiv) was freeze-thawed 3 times at -70 °C and then heated
at 130 °C for 12 h. The reaction mixture was then diluted with DCM
and added dropwise to MeOH. The resultant precipitate was collected
by filtration to give polyS-BS as a white powder, yield 44%. Mn(THF)
1
) 7800 and PD ) 2.42; H NMR (CDCl3) δ 7.35-6.05 (br m, Ar-
1
H), 2.15-1.1 (br m, includes tert-butyl group); H signal integration,
2.5:1 ratio of styrene:4-tert-butylstyrene residues; 13C NMR (CDCl3)
δ 148.18, 145.10, 142.54, 127.31, 125.65, 124.67, 40.38, 34.26, 31.49.
Polystyrene-Poly(3,4-dimethoxystyrene) (S-DS). Reaction: 53
mg of polyS (0.51 mmol of styrene residues estimated, 1 equiv) and
3,4-dimethoxystyrene (7, 0.114 mL, 0.77 mmol, 1.5 equiv). Precipita-
tion: DCM/methanol to give a white powder, yield 33%. Mn(THF) )
1
8500 and PD ) 2.00; H NMR (CDCl3) δ 7.25-5.75 (br m, Ar-H),
3.95-3.4 (br d, -OCH3), 2.2-1.2 (br m); 1H signal integration, 1.9:1
ratio of styrene:3,4-dimethoxystyrene residues; 13C NMR (CDCl3) δ
148.41, 146.95, 145.27, 136.48, 127.96, 125.65, 119.46, 110.62, 55.67,
40.37.
Polystyrene-Poly(N-vinylpyrrolidinone) (S-VP). Reaction: 42
mg of polyS (0.40 mmol of styrene residues estimated, 1 equiv)
dissolved first in 0.07 mL of DMF, N-vinylpyrrolidinone (8, 0.344 mL,
3.2 mmol, 8 equiv), heated for 40 h. Precipitation: THF/methanol to
give a white powder, yield 5%. Mn(THF) ) 8400 and PD ) 1.75; 1H
NMR (CDCl3) δ 7.25-6.8 (br m, Ar-H), 6.8-6.2 (br m, Ar-H),
4.05-3.5 (br m, CH), 3.5-3.05 (br s, CH2), 2.55-1.2 (br m); 1H signal
integration, 3.2:1 ratio of styrene:N-vinylpyrrolidinone residues; 13C
NMR (CDCl3) δ 176.23, 145.16, 127.66, 125.62, 44.10, 43.48, 42.30,
40.36, 18.11.
Blockpolymer Synthesis. 1. Homopolymers. Polystyrene (S).
A solution of 300 mg of 1 (300 mg, 0.39 mmol) and styrene (5, 0.89
mL, 7.75 mmol) in DCB (3 mL) was freeze-thawed 3 times with liquid
nitrogen and then heated at 70 °C for 8 h. The solution was precipitated
by dilution in DCM followed by dropwise addition into MeOH to give
a white solid, yield 80%. Mn(THF) ) 8000 and PD ) 2.11; 1H NMR
(CDCl3) δ 7.25-6.8 (br m, Ar-H), 6.8-6.2 (br m, Ar-H), 2.1-1.65
Polystyrene-Poly(N-isopropylacrylamide) (S-IA). Reaction: 43
mg of polyS (0.41 mmol of styrene residues estimated, 1 equiv)
dissolved first in 0.07 mL of DMF, N-isopropylacrylamide (9, 0.284
g, 2.5 mmol, 6 equiv), heated for 40 h. Precipitation: THF/diethyl
ether to give polyS-IA as a white powder, yield 16%. Mn(THF) )
16 200 and PD ) 1.61; 1H NMR (CDCl3) δ 7.25-6.2 (br m), 4.1-3.9
1
(br s, NCH), 2.4-0.95 (br m, includes -CH3); H signal integration,