The first direct synthesis of β-unsubstituted meso-decamethylcalix[5] pyrrole

Article abstract of DOI:10.3762/bjoc.5.2

The first direct synthesis of ss-unsubstituted meso-decamethylcalix[5] pyrrole from pyrrole and acetone, with moderate yield, is described. The results showed that a bismuth salt was necessary to obtain calix[5]pyrrole, with the best results obtained usingBi(NO3)3.

Full text of DOI:10.3762/bjoc.5.2

The first direct synthesis of β-unsubstituted
meso-decamethylcalix[5]pyrrole
Luis Chacón-García*, Lizbeth Chávez, Denisse R. Cacho
and Josue Altamirano-Hernández
Preliminary Communication
Open Access
Address:
Beilstein Journal of Organic Chemistry 2009, 5, No. 2.
Laboratorio de Diseño Molecular, Instituto de Investigaciones
Químico Biológicas, Edificio B-1 Ciudad Universitaria CP 58030,
Morelia, Mich., México, Fax: +52 443 3265788, Tel: +52 443 3265790
doi:10.3762/bjoc.5.2
Received: 06 November 2008
Accepted: 13 January 2009
Published: 28 January 2009
Email:
Luis Chacón-García* - lchacon@umich.mx
© 2009 Chacón-García et al; licensee Beilstein-Institut.
License and terms: see end of document.
* Corresponding author
Keywords:
bismuth; calix[5]pyrrole; calix[n]pyrrole
Abstract
The first direct synthesis of β-unsubstituted meso-decamethylcalix[5]pyrrole from pyrrole and acetone, with moderate yield, is
described. The results showed that a bismuth salt was necessary to obtain calix[5]pyrrole, with the best results obtained using
Bi(NO3)3.
Results and Discussion
Calix[n]pyrroles have attracted attention because of their ability 40% yield [6,7]. On the other hand, β-unsubstituted
to recognize anions [1,2]. To date, the calix[4]pyrroles have calix[5]pyrroles have been obtained by two routes: a) from the
been studied the most, in part due to the ease with which the corresponding meso-decamethylcalix[5]furan, via a method
macrocycle can be obtained by the condensation of pyrrole with analogous to that reported for calix[6]pyrroles, with 1% yield;
a ketone catalyzed by a Brønsted-Lowry acid such as HCl or and b) directly when the macrocycle is covalently bound to a
methanesulfonic acid, or a Lewis acid such as zeolites with calix[5]arene, with 10% yield [8,9]. However, these approaches
aluminium or cobalt, BF3 or a bismuth salt [2-5]. The synthesis afford calix[5]pyrroles in low yield, which has limited the study
of calix[n]pyrroles where n > 4 has been reported for n = 5 or 6. of these compounds as anion receptors.
The latter compounds have been synthesized via two routes: a)
from the sterically hindered diaryldi(pyrrol-2-yl)methane with One explanation for why it is difficult to obtain calix[5]pyrroles
25% yield; and b) through the conversion of a calix[6]furan into via direct condensation of a pyrrole and the corresponding
the corresponding calix[6]pyrrole by an opening process of the ketone is that the five heterocycle system is unstable: it opens
six heterocycles, a selective reduction of the double bond and and loses a pyrrole-isopropyl fragment to give the
then a Paal-Knorr condensation with ammonium acetate with calix[4]pyrrole [8,10].
Page 1 of 3
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Beilstein Journal of Organic Chemistry 2009, 5, No. 2.
In a recent report we described the synthesis of calix[4]pyrroles listed in Table 1. Compounds 1 and 2 were almost indistin-
via the direct condensation of pyrrole with a series of ketones in guishable on TLC because of their similar Rf values, and recrys-
the presence of a bismuth salt such as Bi(NO3)3, BiCl3, BiI3, tallization from ethanol, as reported in other works, was not
and Bi(CF3SO3)3, in a 1 : 1 : 0.25 (pyrrole : ketone : BiX3) ratio satisfactory to give the pure compounds. However, it was
or with the ketone as a solvent at room temperature [5]. Here possible to separate 1 and 2 by HPLC, to obtain 2 in 25% yield
we describe the first direct synthesis of β-unsubstituted meso- (using the conditions specified in Table 1, entry 12). Compound
decamethylcalix[5]pyrrole (2) with Bi(NO3)3 in moderate yield 2 was found to be unstable, which probably decreased the yield.
(Scheme 1).
To determine whether the reaction proceeds with other Lewis
While studying the role of bismuth as a Lewis acid in the acids, we explored the use of MgCl2, CuCl2, ZnCl2, AlCl3,
synthesis of calix[4]pyrroles, we found that at low catalyst BiCl3, BiI3, BiPO4, Bi(OTf)3 and Bi(NO3)3 under the condi-
concentrations some additional products were formed, as tions described above. Except for MgCl2, which gave none of
observed by 1H NMR spectroscopy. These byproducts exhib- the byproducts, all of these Lewis acids catalyzed the reaction
ited 1H NMR, 13C NMR and MS data consistent with those to give 1 and/or 4 in amounts ranging from traces to moderate
reported for calix[n]pyrroles with n = 4, 5 and 6 (compounds yields. Bismuth salts also produced 3. The results showed that a
1–3, respectively) and 5,5-dimethyldipyrromethane (4); see bismuth salt was necessary to obtain calix[5]pyrrole 2, with the
Experimental section [5,6,8]. The relative proportions of these best results being obtained with Bi(NO3)3. The advantages of
four products obtained using different catalyst equivalents are the method described here—namely that bismuth is relatively
non-toxic, the macrocycle is obtained in moderate yield, and the
synthesis proceeds without any intermediates—make it the best
route to β-unsubstituted meso-decamethylcalix[5]pyrrole
reported to date.
Experimental
meso-Decamethylcalix[5]pyrrole (2). In a typical reaction, 6 mg
of Bi(NO3)3, 2 mL of acetone and 0.09 mL of pyrrole were
mixed with stirring at room temperature for 6 h. The reaction
mixture was filtered and the solvent evaporated without heat.
Reactants were not distilled prior to use and heat was avoided
Scheme 1: Products obtained by the reaction of pyrrole and acetone
with bismuth(III).
throughout the process. meso-Decamethylcalix[5]pyrrole was
purified from the crude reaction mixture using an Agilent Tech-
Table 1: Catalyst conditions and relative proportions of compounds 1, 2, 3 and 4 detected in the crude reaction mixture by 1H NMR spectroscopy.
Entry
Catalyst
% mol
1
2
3
4
1
MgCl2 · 6H2O
CuCl2 · 2H2O
ZnCl2
9.5
–
–
–
–
2
9.5
100
80
–
–
–
–
3
9.5
–
–
20
100
–
4
AlCl3
5
–
–
5
BiCl3
9.5
50
44
53
80
–
40
42
45
20
–
10
12
–
6
BiI3
9.5
2
7
BiPO4
9.5
2
8
Bi(OTf)3
Bi(NO3)3
Bi(NO3)3
Bi(NO3)3
Bi(NO3)3
Bi(NO3)3
Bi(NO3)3
Bi(NO3)3
9.5
–
–
9
0.095
0.18
0.32
0.65
0.95
9.5
–
100
60
–
10
11
12
13
14
15a
40
50
33
90
95
100
–
–
50
67
10
<5
–
–
–
–
–
–
–
–
25
–
–
aAs reported in [5].
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Beilstein Journal of Organic Chemistry 2009, 5, No. 2.
10.Sessler, J. L.; Anzenbacher, P., Jr.; Shriver, J. A.; Jursíková, K.;
Lynch, V. M.; Marquez, M.
nologies HPLC 1200 system equipped with a multiple
wavelength detector (G1365D) operating at 350 nm. Purifica-
tion was performed on an analytical Zorbax Eclipse XDB-C18
column (150 × 4.6 mm, Agilent Tech. Santa Clara, CA, USA).
The column temperature was maintained at room temperature
and the mobile phases consisted of solvent A (80% MeOH/20%
H2O) and solvent B (100% EtOAc). Separations were
performed by the following solvent gradient: 0 min 20% B, 2.5
min 22.5% B, 20–22.5 min 50% B, 24–26 min 80% B, 31–34
min 100% B, 42–47 min 20% B. All increases of solvent B
were linearly programmed. The flow rate was 1 mL/min and the
injection volume 20 µL. Yield ca. 25%; mp 208–210 °C; 1H
NMR (400 MHz, CDCl3): 1.51 (s, 30H, CH3), 5.77 (d, J = 2.8
Hz, 10H, CH), 7.54 (bs, 5H, NH); 13C NMR: 29.3 (CH3), 35.3
(C(CH3)2), 102.8 (CH), 138.5 (β-C pyrrole); EIMS m/z: 535
(M•+).
J. Am. Chem. Soc. 2000, 122, 12061–12062. doi:10.1021/ja005650h
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Acknowledgments
We thank for financial support from CONACYT (47907) and
doi:10.3762/bjoc.5.2
CIC- UMSNH (2.19).
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