LETTER
Synthesis of Calix[4]pyrrole-Based Acrylate
1173
+
pected to play an important role in the preparation of en-
vironmentally stable ion-sensitive polymer membranes
for use in various anion sensors.
(MALDI-TOF): 765.54 [MH ]. Anal. Calcd for C44
(
6
H
52
N
4
O
8
764.91): C, 69.09; H, 6.85; N, 7.32. Found: C, 68.94; H,
.88; N, 6.99.
Compound 3: yield 29% (A), 60% (B); mp >200 °C (dec.).
1
H NMR (250 MHz, CDCl ): d = 1.47–1.58 (m, 18 H, CH ),
3
3
2
.23–2.28 (m, 4 H, CH ), 4.03–4.08 (m, 4 H, OCH ), 5.80
Acknowledgment
2
2
(
dd, J = 8.5, 1.3 Hz, 2 H, cis CH =CH), 5.90–5.95 (m, 8 H,
2
Support for this research from the NSF (SENSORS #0330267 to
P.A., EXP-LA #0731153 to P.A., T.K.), support from the Alfred P.
Sloan Foundation (P.A.), and BGSU (Technology Innovations En-
hancement grant) is gratefully acknowledged. We would like to
thank Lic. Manuel Palacios for helpful discussion on the topic of ca-
lix[4]pyrrole synthesis.
HetH), 6.11 (dd, J = 14.0, 8.3 Hz, 2 H, CH =CH), 6.35 (dd,
2
J = 15.0, 1.5 Hz, 2 H, trans CH =CH), 7.04 (br s, 4 H, NH).
2
1
3
C NMR (75 MHz, CDCl ): d = 27.5, 29.0, 30.1, 35.2, 37.6,
3
43.9, 61.6, 103.0, 104.0, 128.5, 130.4, 137.2, 138.7, 166.1.
+
MS (MALDI-TOF): 596.26 [M ]. Anal. Calcd for
C H N O (596.76): C, 72.46; H, 7.43; N, 9.39. Found: C,
3
6
44
4
4
7
2.55; H, 7.68; N, 9.11.
7) Synthesis of 5
Similarly to the reported procedure, to a solution of pyrrole
1.7 mL, 24 mmol) and 4-hydroxybutan-2-one (2.1 mL, 24
(
References and Notes
9
(
(
1) (a) Sessler, J. L.; Gale, P. A.; Cho, W.-S. In Anion Receptor
Chemistry. Monographs in Supramolecular Chemistry; RSC
Publishing: Cambridge, 2006. (b) Suksai, C.; Tuntulani, T.
Top. Curr. Chem. 2005, 255, 163. (c) Martínez-Máñez, R.;
Sancenón, F. Chem. Rev. 2003, 103, 4419.
mmol) in 50% aq EtOH (15–20 mL), concd HCl (1–1.5 mL)
was added dropwise over 1 h at r.t. under Ar. After 0.5 h a
precipitate formed. The dark solution was stirred for
additional 1–2 h, then filtered, and the precipitate was
washed with H O and small amount of MeOH, dried, and
(
(
2) Bayer, A. Ber. Dtsch. Chem. Ges. 1886, 19, 2184.
3) (a) Gale, P. A.; Sessler, J. L.; Král, V.; Lynch, V. J. Am.
Chem. Soc. 1996, 118, 5140. (b) Gale, P. A.; Sessler, J. L.;
Král, V. Chem. Commun. 1998, 1. (c) Gale, P. A.;
2
recrystallized from MeOH–CH Cl (1:1) to afford a white
2
2
solid.
Synthesis of 6
1
0
To a solution of dipyrromethane (1 mmol) and ketone (1
mmol) in MeOH (5 mL), MsOH (0.1 mL) was added
dropwise over 0.5 h at r.t. under Ar. The dark solution was
stirred until the precipitation occurred or for 2–3 h. The
solution was then evaporated under reduced pressure, treated
Anzenbacher, P. Jr.; Sessler, J. L. Coord. Chem. Rev. 2001,
2
22, 57. (d) Anzenbacher, P. Jr.; Jursikova, K.; Lynch, V.
M.; Gale, P. A.; Sessler, J. L. J. Am. Chem. Soc. 1999, 121,
1020.
4) (a) Nishiyabu, R.; Anzenbacher, P. Jr. J. Am. Chem. Soc.
005, 127, 8270. (b) Nishiyabu, R.; Anzenbacher, P. Jr.
1
(
with H O, and the precipitate that formed was filtered off,
2
2
washed with H O and small amount of MeOH, dried, and
Org. Lett. 2006, 8, 359. (c) Nishiyabu, R.; Palacios, M. A.;
Dehaen, W.; Anzenbacher, P. Jr. J. Am. Chem. Soc. 2006,
2
recrystallized from MeOH–CH Cl (1:1) to afford a white
2
2
solid.
Compound 5: yield 50%; mp >200 °C (dec.). H NMR (250
MHz, CDCl and DMSO-d ): d = 1.39 (br s, 12 H, CH ),
128, 11496. (d) Palacios, M. A.; Nishiyabu, R.; Marquez,
1
M.; Anzenbacher, P. Jr. J. Am. Chem. Soc. 2007, 129, 7538.
5) Anzenbacher, P. Jr.; Nishiyabu, R.; Palacios, M. A. Coord.
Chem. Rev. 2006, 250, 2929.
(
(
3
6
3
3
2
5
.03–2.10 (m, 8 H, CH ), 3.34 (t, J = 5.7 Hz, 8 H, OCH ),
.68–5.77 (m, 8 H, HetH), 7.58 (br s, 4 H, NH). C NMR
2
2
1
3
6) Synthesis of 2 and 3
(
1
75 MHz, CDCl and DMSO-d ): d = 26.5, 37.5, 43.0, 58.9,
Method A
3
6
+
03.2, 137.44. MS (MALDI-TOF): m/z = 549.59 [MH ].
To the corresponding substrate (1 mmol) and anhyd Et N
3
Anal. Calcd for C H N O (548.34): C, 70.04; H, 8.08; N,
(
2.5 equiv for each hydroxy group) in anhyd CH Cl (80 mL)
32 44
4
4
2
2
1
0.21. Found: C, 69.94; H, 8.37; N, 9.99.
Compound 6: yield 60%; mp >200 °C (dec.). H NMR (250
MHz, CDCl ): d = 1.50 (br s, 6 H, CH ), 1.53 (br s, 12 H,
at –10 °C to 0 °C under Ar, acryloyl chloride (1.1 equiv for
each hydroxy group) was added dropwise over 0.5 h. The
reaction mixture was stirred for another 0.5 h, warmed to r.t.
and left to stir overnight. The reaction mixture was then
washed with sat. NaHCO , H O (2 × 30 mL), dried over
1
3
3
3
CH ), 2.13–2.18 (m, 4 H, CH ), 3.58 (t, J = 5.0 Hz, 4 H,
3
2
OCH ), 5.88–5.95 (m, 8 H, HetH), 7.04 (br s, 4 H, NH). 13C
2
3
2
NMR (75 MHz, CDCl ): d = 26.6, 29.1, 29.3, 35.2, 37.5,
MgSO , and evaporated to dryness. Recrystallization from
3
4
4
2.9, 59.5, 102.8, 103.8, 138.5, 139.2. MS (MALDI-TOF):
MeOH–CH Cl or flash chromatography (SiO , 0–5%
2
2
2
+
m/z = 489.59 [MH ]. Anal. Calcd for C H N O (488.66):
MeOH in CHCl ) afforded the product as a white solid.
30 40
4
2
3
C, 73.74; H, 8.25; N, 11.47. Found: C, 74.04; H, 8.37; N,
1.79
Method B
1
To the corresponding substrate (0.5 mmol) and anhyd (i-
(
8) Synthesis of 8
Pr) NEt (2.5 equiv for each hydroxy group) in anhyd DMF
2
To a solution of pyrrole (1 mmol) and ketone 711 (1 mmol)
in MeOH (5 mL), MsOH (0.1 mL) was added dropwise over
(
25 mL) at –10 °C to 0 °C under Ar, the solution of N-
hydroxysuccinimidyl acrylate (1.1 equiv for each hydroxy
group) in anhyd DMF (1 mL) was added dropwise over 0.5
h. The reaction mixture was stirred for another 0.5 h,
warmed to r.t. and left to stir overnight. The reaction mixture
was then evaporated to dryness and diluted with CH Cl .
0.5 h at r.t. under Ar. The dark solution was stirred until the
precipitation occurred or for 2–3 h. The solution was then
evaporated under reduced pressure, treated with H O, and
2
the precipitate that formed was filtered off, washed with H O
2
2
2
and small amount of MeOH, dried and recrystallized from
After that the procedure is similar to method A.
MeOH–CH Cl (1:1) to afford a white solid of 8.
Compound 8: yield 59%; mp 171–173 °C (dec.). H NMR
Compound 2: yield 15% (A), 31% (B); mp >200 °C (dec.).
2
2
1
1
H NMR (250 MHz, CDCl and DMSO-d ): d = 2.19–2.21
3
6
3
(250 MHz, CDCl ): d = 1.18–1.34 (m, 20 H, CH and CH ),
(
m, 8 H, CH ), 2.44–2.50 (m, 12 H, CH ), 3.92 (t, J = 5.7
3
2
3
2
3
1.97–2.05 (m, 8 H, CH ), 3.47–3.69 (m, 8 H, NCH ), 5.83–
2 2
Hz, 8 H, CH ), 5.69 (dd, J = 8.8, 1.3 Hz, 4 H, cis CH =CH),
2
2
5
.97 (m, 8 H, HetH), 7.02 (br s, 2 H, NH), 7.09 (br s, 2 H,
5.80 (d, J = 2.3 Hz, 8 H), 5.95 (dd, J = 14.5, 8.8 Hz, 4 H,
1
3
NH), 7.62–7.80 (m, 16 H, ArH). C NMR (75 MHz,
CH =CH), 6.23 (dd, J = 14.5, 1.5 Hz, 4 H, trans CH =CH),
2
2
1
3
CDCl ): d = 23.4, 23.6, 23.9, 26.1, 26.2, 26.4, 37.3, 38.3,
8
.23 (br s, 4 H, NH). C NMR (75 MHz, CDCl ): d = 26.3,
3
3
38.4, 39.0, 104.0, 123.0, 123.1, 132.1, 133.6, 133.7, 133.8,
37.7, 38.7, 61.7, 104.3, 128.6, 130.4, 136.6, 166.0. MS
Synlett 2008, No. 8, 1171–1174 © Thieme Stuttgart · New York