D.M. Kelly, H.A. Moynihan / Tetrahedron 66 (2010) 5459e5466
5465
dropwise to the reaction mixture at 0 ꢀC. Stirring was continued for
4.5. General procedure for acrylating 8a and 8b25
1 h at 0 ꢀC and then overnight at room temperature. The reaction
mixture was then cooled to below 4 ꢀC for 30 min to promote the
precipitation of the white crystalline side product, DCU. This was
then filtered from the reaction mixture and the filtrate was collected
and evaporated using a rotary evaporator to remove the bulk of the
DMF. The remaining solution was poured onto ice with stirring and
left overnight to remove residual DMF and HOBt. The product was
collected by suction filtration to afford a white solid.
The functionalised hydrochloride salt (7.35 mmol) and sodium
hydroxide (1.03 g, 25.73 mol) were added to water (14.5 ml) and
the mixture was cooled to 0 ꢀC. The excess sodium hydroxide
served to keep the pH above 12. Acryloyl chloride (0.67 ml,
8.3 mmol) was added in 0.1 ml portions every 2 min over a 12 min
period to the rapidly stirred aqueous suspension. After an addi-
tional 2 min stirring, the reaction mixture was acidified to pH 2.6 by
the drop-wise addition of concd HCl while maintaining the tem-
perature at 0 ꢀC. The product precipitated out of solution and was
collected by filtration and washed with ice cold water to afford
a light pink solid.
4.3.1. 5-(6-(tert-Butoxycarbonylamino)hexanamido)isophthalic acid
(7a). Obtained using DCC coupling of N-protected amino acid 6a to
afford 7.19 g (91%): mp 179e182 ꢀC; IR (KBr)
n
3361, 3315, 1683,
1605, 1538, 1282, 1167; 1H NMR (DMSO-d6)
d 1.23e1.40 (2H, m),
1.35 (9H, s), 1.56e1.61 (4H, m), 2.32 (2H, t, J¼7.5 Hz), 2.90 (2H, q,
4.5.1. 5-(6-Acylamidohexanamido)isophthalic acid (9a). Obtained
by reaction of acryloyl chloride with 4c to afford 0.97 g (38%): mp
J¼9 Hz), 6.79 (1H, t, J¼6 Hz), 8.14 (1H, s), 8.43 (2H, s), 10.24 (1H, br
s), 12.72 (2H, br s); 13C NMR (DMSO-d6)
d
24.70, 25.89, 28.21, 29.27,
138e142 ꢀC; IR (KBr)
(DMSO-d6) d 1.09e1.32 (2H, m), 1.33e1.69 (4H, m), 2.27 (2H, t,
n
3372, 3215, 1702, 1656, 1564, 1260; 1H NMR
33.30, 36.33, 77.26, 123.35, 124.31, 131.60, 139.81, 155.55, 166.60,
171.68. Anal. Calcd for C19H26N2O7: C, 57.86; H, 6.64; N, 7.10. Found:
C, 57.86; H, 7.16; N, 7.62.
J¼7.5 Hz), 3.11e3.15 (2H, m), 5.48 (1H, dd, J¼3, 9 Hz), 5.98 (1H, dd,
J¼3, 18 Hz), 6.15 (1H, dd J¼10.5, 16.5 Hz), 7.80 (1H, s), 7.89 (2H, br s),
8.11 (1H, s), 8.45 (2H, s), 10.21 (1H, br s); 13C NMR (DMSO-d6)
d 25.4,
4.3.2. 5-(6-(tert-Butoxycarbonylamino)dodecanamido)isophthalic
26.1, 26.7, 28.8, 33.3, 40.3, 123.0, 124.6, 131.9, 133.3, 139.4, 164.4,
167.3, 171.6. MS m/z (%) 349 (Mþ, 30), 278 (16), 266 (25), 264 (18),
225 (60), 190 (10), 136 (10), 130 (19), 115 (100), 74 (60), 64 (18).
Calcd for C17H21N2O6: M, 349.1400. Found: m/z 349.1389.
acid (7b). Obtained using DCC coupling of N-protected amino acid
6b to afford 8.20 g (86%): mp 182e184 ꢀC; IR (KBr)
n
3352, 1687
(CO), 1607, 1541, 1280, 1169; 1H NMR (DMSO-d6)
d 1.27 (14H, br s),
1.44 (9H, s), 1.42e1.44 (2H, m) 1.61e1.65 (2H, m), 2.34 (2H, t,
J¼7.5 Hz), 2.91e2.96 (2H, q, J¼12 Hz), 6.71 (1H, br s), 8.14 (1H, s),
8.28 (2H, s), 10.21 (1H, br s), 12.72 (2H, br s); 13C NMR (DMSO-d6)
4.5.2. 5-(12-Acylamidododecanamido)isophthalic acid (9b). Obtained
by reaction of acryloyl chloride with 5c to afford 2.77 g (87%): mp
d
26.2, 28.2, 28.6, 28.8, 28.9, 28.9, 28.9, 29.4, 36.4, 40.3, 77.2, 123.3,
140e143 ꢀC; IR (KBr)
NMR (DMSO-d6) d 1.39 (14H, br s), 1.42e1.45 (2H, m), 1.47e1.50 (2H,
n
3283, 3115, 1702, 1657, 1622, 1552, 1229; 1H
124.3, 131.8, 139.8, 155.5, 166.5, 171.8. Anal. Calcd for C25H38N2O7: C,
62.74; H, 8.00; N, 5.85. Found: C, 63.22; H, 8.28; N, 6.40.
m), 2.24 (2H, t, J¼7.5 Hz), 2.99e3.06 (2H, q, J¼12 Hz), 5.48 (1H, dd,
J¼3, 9 Hz), 5.98 (1H, dd J¼3, 15 Hz), 6.14 (1H, dd J¼9.6, 17.2 Hz), 8.02
(1H, s), 8.30 (2H, s), 10.11 (1H, br s), 12.72 (2H, br s); 13C NMR (DMSO-
4.4. General procedure for the trifluoroacetic acid cleavage of
the functionalised tert-butyl cpds 7a and 7b and the
subsequent formation of their hydrochloride salts6
d6) d 25.8, 26.4, 27.1, 28.3, 28.4, 28.5, 28.7, 28.9, 36.4, 38.5, 122.9,
124.6, 131.9, 133.2, 139.4, 164.4, 167.1, 167.4, 171.6. MS m/z (%) 433
(Mþ, 50), 381 (2), 380 (18), 379 (100), 339 (6), 270 (12), 244 (6), 192
(4), 116 (4), 115 (74), 75 (5), 74 (78). Calcd for C23H33N2O6: M,
433.2339. Found: m/z 433.2331.
To a solution of the functionalised tert-butyl compound (2 mmol)
in DCM (10 ml) was added trifluoroacetic acid (10 ml) in one portion
at room temperature. The reaction mixture was stirred for 1 h and
then evaporated under vacuum to remove the solvent and pumped
dry using a high vacuum pump. This afforded the crude tri-
fluoroacetate salt as a light pink solid. This was then dissolved in
ethanol (2 ml) containing 1 ml of concd HCl. The mixture was evap-
oratedundervacuumtoaffordthehydrochloridesaltasayellowsolid.
4.6. General procedure for the preparation of the
functionalised polymers (10a) and (10b) with 100%
functionality3
The acryloyl compound (1.2 g, 3.45 mmol) was polymerized in
DMF (10 ml) at 80 ꢀC for 72 h with AIBN (30 mg, 0.18 mmol). The bulk
of the DMF was removed using rotary evaporation and the resulting
polymer was precipitated fromwaterand filtered to give ayellowsolid.
4.4.1. 5-(3,5-Dicarboxyphenylcarbamoyl)pentylammonium chloride
(8a). Obtained by trifluoroacetic acid cleavage of 7b to afford 0.64 g
(97%): mp 300e301 ꢀC (decomp.); IR (KBr)
n
2931, 1699, 1654, 1609,
1.20e1.41 (2H, m), 1.43e1.73 (4H,
m), 2.32 (2H, t, J¼7.5 Hz), 2.70e2.81 (2H, m), 7.89 (2H, br s), 8.11
(1H, s), 8.45 (2H, s), 10.41 (1H, br s); 13C NMR (DMSO-d6)
24.4,
4.6.1. Poly-N-(5-(N0-(3,5-dicarboxyphenyl)carbamoyl)pentyl)acryl-
1565, 1219; 1H NMR (DMSO-d6)
d
amide (10a). Compound 10a (1.05 g, 88% recovery): mp above
250 ꢀC (decomp.); IR (KBr)
n H
3338, 3115, 1708, 1651, 1556, 1219; 1
d
NMR (DMSO-d6) d 1.09e1.32 (2H, br m), 1.33e1.69 (4H, m),
25.4, 26.7, 33.3, 36.0, 123.4, 124.3, 131.6, 139.9, 166.5, 171.6. MS m/z
(%) 295 (Mþ, 100), 225 (2), 191 (6), 177 (10), 136 (16), 130 (42), 105
(4). Calcd for C14H19N2O5: M, 295.1294. Found: m/z 295.1284.
2.24e2.27 (2H, m), 3.10e3.15 (2H, m), 7.89 (2H, br s), 8.11 (1H, s), 8.45
(2H, s), 8.82 (1H, s), 10.21 (1H, br s); Mw 84,000 Da; Mw/Mn 17.5.
4.6.2. Poly-N-(11-(N0-(3, 5-dicarboxyphenyl)carbamoyl)undecyl)ac-
4.4.2. 11-(3,5-Dicarboxyphenylcarbamoyl)undecylammonium chlo-
rylamide (10b). Compound 10b (1.49 g, 100% recovery): mp above
ride (8b). Obtained by the trifluoroacetic acid cleavage of 7b to
250 ꢀC (decomp.); IR (KBr)
n
(KBr) 3337, 3114, 1705, 1652, 1555,
afford 0.78 g (97%): mp 300 ꢀC (decomp.); IR (KBr)
n
3490, 2922,
1218; 1H NMR (DMSO-d6)
d 01.01e1.42 (14H, br s), 1.42e1.45 (2H,
1710, 1606, 1562, 1204; 1H NMR (DMSO-d6)
d
1.19 (14H, m),
m), 1.43e1.56 (2H, m), 2.34 (2H, t, J¼7.5 Hz), 2.70e3.74 (2H, q,
J¼12 Hz), 8.10 (1H, s), 8.43 (2H, s), 10.23 (1H, br s), 12.72 (2H, br s);
Mw 68,000 Da, Mw/Mn 26.2.
1.38e1.42 (2H, m) 1.47e1.52 (2H, m), 2.26 (2H, t, J¼7.5 Hz),
2.66e2.82 (2H, q, J¼12 Hz), 7.67 (3H, br s), 8.07 (1H, s), 8.38 (2H, s),
10.25 (1H, br s), 12.72 (2H, br s); 13C NMR (DMSO-d6)
d 25.0, 25.8,
26.9, 28.5, 28.7, 28.8, 40.0, 123.4, 131.8, 139.8, 166.5, 171.8. MS m/z
(%) 379 (Mþ, 100), 285 (4), 244 (5), 216 (16), 130 (4), 115 (34), 74
(25). Calcd for C20H31N2O5: M, 379.2233. Found: m/z 379.2223.
4.6.3. 5-Acetamidoisophthalic acid (11)21. To a stirred solution of 5-
aminoisophthalic acid 2 (3.62 g, 20 mmol) in DMF (30 ml), acetic
anhydride (2.83 ml, 30 mmol) and acetic acid (0.6 ml, 10 mmol)