Hetero-calix[4]pyrroles: Incorporation of furans, thiophenes, thiazoles or fluorenes as a part of the macrocycle

Article abstract of DOI:10.1016/j.tetlet.2003.10.170

Furans, thiazoles, fluorene or thiophene incorporated calix[4]pyrrole analogues were synthesized and characterized. The synthesis was achieved by utilization of various building blocks such as 7, 13, 14, 18 and 21. Acid catalyzed condensation of those building blocks with acetone or meso-disubstituted dipyrromethanes afforded desired macrocycles.

Full text of DOI:10.1016/j.tetlet.2003.10.170

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 299–301
Hetero-calix[4]pyrroles: incorporation of furans, thiophenes,
thiazoles or fluorenes as a part of the macrocycle
q
a
Mi-Young Song, Hee-Kyung Na, En-Young Kim, Si-Joon Lee, Kyung Il Kim,
a
a
a
b
b
b
a
Eun-Mi Baek, Hong-Seok Kim, Duk Keun An and Chang-Hee Lee
a,
*
a
Department of Chemistry, Kangwon National University, Chun-Chon 200-701, South Korea
Department of Industrial Chemistry, Kyungpook National University, Dae-Gu 702-701, South Korea
b
Received 31 August 2003; revised 12 October 2003; accepted 29 October 2003
Abstract—Furans, thiazoles, fluorene or thiophene incorporated calix[4]pyrrole analogues were synthesized and characterized. The
synthesis was achieved by utilization of various building blocks such as 7, 13, 14, 18 and 21. Acid catalyzed condensation of those
building blocks with acetone or meso-disubstituted dipyrromethanes afforded desired macrocycles.
Ó 2003 Elsevier Ltd. All rights reserved.
6
Anion binding chemistry using neutral molecules has
been one of the important areas in the field of molecular
recognition due to their potential biological applica-
meso-alterations or attachment of fluorescent chromo-
7
phores at the periphery of calix[4]pyrrole.
1
–3
tions. A number of newer and specifically function-
alized receptors binding selectively with anionic
substrates have been developed as a result of these
efforts. The anion binding mainly occurs through weak
hydrogen bonding or electrostatic interactions and thus
is usually weaker than cation binding. Among the
anionic receptors, calix[4]pyrroles have been verified as
one of the selective anion binding molecules for halide
anions. Sessler et al. have synthesized variety of modi-
The systems depicted by structures 1–4 are designed and
synthesized. The relation between structure, number of
H-binding donors and binding affinity may be system-
atically studied with these model systems.
The most common structural variation of calix[4]pyr-
roles are attachment of the same substituents at meso
positions. In this case, the synthesis can be easily
achieved by condensing appropriate ketones with pyr-
role in the presence of acid catalyst. On the other hand,
the systems 1–4 are difficult to obtain by simple pyrrole–
ketone condensation approach. These systems differ
from other functionalized systems in the sense that the
4
fied calix[4]pyrroles and their anion binding properties
have been studied. Recently, we have demonstrated that
the strapping approach is the most useful among the
5
various modifications such as b-pyrrolic substitution,
S
S
N
N
O
S
X
X
NH HN
NH HN
NH HN
NH HN
NH HN
4
2
(X=O, S)
1
3
Keywords: Calix[4]pyrrole; Hetero-calix[4]pyrroles; Anion binding; H-Bonding; Modified calixpyrrole; Dithiazolyl methane; Fluorenone.
q
Supplementary data associated with this article can be found in the online version, at doi:10.1016/j.tetlet.2003.10.170.
*
Corresponding author. Tel.: +82-332508490; fax: +82-332537582; e-mail: chhlee@kangwon.ac.kr
0
040-4039/$ - see front matter Ó 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.10.170

300
M.-Y. Song et al. / Tetrahedron Letters 45 (2004) 299–301
1
. n-BuLi / TMEDA
Furan
NH HN
NH HN
S
2. Acetone
S
BF3
S
O
Pyrrole
Acetone
BF3
OH
6
TFA
5
O
(45%)
NH HN
(31%)
1
2
. n-BuLi
. Acetone
1
7
18
3
Scheme 3.
S
O
BF3
S
O
+
CH3CN
NH HN
NH HN
densation of 9 or 10 with furan (or thiophene) gave
corresponding products 11 and 12 in 87% and 4%,
respectively. Bis-lithiation of 11 and 12 followed by
OH
HO
7
8
11
1
treatment with 3-pentanone resulted in the formation of
diol 13 and 14 in 32% and 36%, respectively. The choice
of the 3-pentanone is purely arbitrary. Then, acid cata-
lyzed condensation of corresponding diol with 5,5-dim-
ethyldipyrromethane 8 afforded the desired products 15
and 16 in 34% and 41%, respectively.
Scheme 1.
12
fluorophores are not only the integral part of the
calix[4]pyrrole system but incorporated heterocycles
such as furan or thiophene other than pyrrole can act as
cationic recognition site. The cation binding character-
The fluorene-attached compound 3 was synthesized as
shown in Scheme 3. 9-Fluorenone 17 and pyrrole were
condensed as usual method and resulting dipyrro-
methane 18 was condensed with acetone in the presence
of BF (Et O) to afford desired product in low yield.
8
istic of calixfuran has been documented. Furan or thio-
phene incorporated calixpyrrole 1 was synthesized as
shown in Scheme 1. Lithiated thiophene was treated
with acetone in THF to afford alcohol 5, which was
converted to furylthienylmethane 6 in 70% yield. Di-
3
2
Compound 3 was rather unstable and slow decomposi-
tion was observed in methylene chloride within 24 h of
time frame. Incorporation of fluorescence probe inside
or a part the rim of the calix[4]pyrrole would dramati-
cally alter the conformation of the host compound and
the anion binding behaviour would be influenced cor-
respondingly.
lithiation of 6 followed by reaction with acetone gave
9
3
3% yield of diol 7. Acid catalyzed condensation of 7
with 5,5-dimethyldipyrromethane 8 then afforded the
desired host 1 in 39% yield. The proton NMRspectrum
shows two pyrrolic N–H signal at 7.28 and 7.25 ppm as
usual.
The first report for the synthesis of modified calixpyr-
The thiazole incorporated compound 4 was synthesized
by condensation of 21 with acetone. As shown in
Scheme 4, the bisthiazolylmethane 20 was reacted with
pyrrole in the presence of acid to afford 21 in low yield.
Direct replacement of benzyl-type chloride with a-car-
bon of pyrrole is quite unusual and the nucleophilicity
of pyrrole must be exceptionally larger under the con-
dition attempted. This reaction is only possible when
pyrrole is used as the reaction solvent. 4 is the first thi-
azole incorporated calix[4]pyrrole analogues to be con-
structed. Attempted condensation of 21 with aldehydes
followed by DDQ oxidation did not give corresponding
10;12
roles appeared in 1955 by W.H. Brown et al.
Although the synthesis of the cyclic oligomers of furan
or thiophene) and acetone have been reported, to the
(
best of our knowledge, the mixed oligomers of furan–
thiophene have not been reported. The preparation
of difurylmethane (or dithienylmethane) containing
calix[4]pyrrole analogues 15 and 16 involves four-step
synthesis starting from furan (or thiophene) as shown in
Scheme 2. Lithiation of furan (or thiophene) followed
by treatment with 3-pentanone afforded alcohols 9 and
11
1
0 in 74% and 67%, respectively. Acid-catalyzed con-
S
S
O
S
S
Thiophene or
Cl
Cl
N
TMEDA, n-BuLi 3-Pentanone
Hexanes
furan
Pyrrole
N
H2N
NH2
N
N
X
THF
X
BF3OEt2
OH
X
X
NH
S
S
HN
Cl
Cl
9
1
(X=O) 74%
X = O, S
1
1
1 (X=O) 87%
2 (X=S) 4%
0 (X=S) 67%
19
20
21
TMEDA
n-BuLi
H+
Acetone
N
BrMg
N
MgBr
3-Pentanone
S
S
X
X
8
N
N
X
X
BF3OEt2
NH HN
OH
HO
NH HN
1
3 (X=O) 32%
1
1
5 (X=O) 34%
6 (X=S) 41%
14 (X=S) 36%
4
Scheme 2.
Scheme 4.

M.-Y. Song et al. / Tetrahedron Letters 45 (2004) 299–301
301
porphyrinoid macro cycle. All the intermediate com-
References and Notes
pounds were isolated by column chromatography and
identified with mass spectrometry and NMRspectros-
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receptors was tested by following the changes in NMR
or fluorescence spectra that were induced by addition of
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anions. Unfortunately, the hosts 1, 2, 4, 15 and 16 did not
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titration analysis with chloride anion (as tetrabutyl
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Supplementary material
Spectroscopic data for all the reported compounds can
be found in the online version of this article.
9
. The monohydroxymethylated compound bearing one
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1
1
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Support from the Korea Research Foundation Grant
(
KRF-2001-005-D20012) is gratefully acknowledged.
The Vascular System Research Center (VSRC) at KNU
is acknowledged for support.
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Chem. Soc. 1996, 118, 5140–5141.