Ytterbium(III) triflate catalyzed synthesis of calix[4]pyrroles in ionic liquids

Article abstract of DOI:10.1139/V08-121

Ytterbium(III) triflate has been utilized as a mild Lewis-acid catalyst for the synthesis of various calix[4]pyrroles by the condensation of pyrrole with different ketones in ionic liquids. The calix[41pyrroles were obtained. in high yield under ecofriend

Full text of DOI:10.1139/V08-121

899
Ytterbium(III) triflate catalyzed synthesis of
calix[4]pyrroles in ionic liquids
Anil Kumar, Israr Ahmad, and M. Sudershan Rao
Abstract: Ytterbium(III) triflate has been utilized as a mild Lewis-acid catalyst for the synthesis of various
calix[4]pyrroles by the condensation of pyrrole with different ketones in ionic liquids. The calix[4]pyrroles were obtained
in high yield under ecofriendly, economical, and noncorrosive conditions, and the catalyst was recovered and recycled.
Key words: calix[4]pyrrole, ionic liquid, ytterbium triflate.
Résumé : On a utilisé le triflate d’ytterbium(III) comme catalyseur acide de Lewis doux pour la synthèse de divers ca-
lix[4]pyrolles par condensation du pyrrole avec diverses cétones dans des liquides ioniques. Les calix[4]pyrolles ont été
obtenus avec des rendements élevés dans des conditions économiques, non corrosives et respectueuses de
l’environnement alors que le catalyseur peut être récupéré et recyclé.
Mots-clés : calix[4]pyrolle, liquide ionique, triflate d’ytterbium.
[Traduit par la Rédaction] Kumar et al. 902
Introduction
Fig. 1. Imidazolium ionic liquid.
Calix[4]pyrroles, a class of tetrapyrrolic macrocyclic mol-
ecules, have been known for a long time but recently have
become the subject of intensive research because of their
properties for binding with anions, transition metals, and
neutral molecules (1). Their anion-binding properties has
been extensively studied as a result of their potential biologi-
cal applications (2). Calix[4]pyrroles were first synthesized
over a century before by the condensation of acetone and
pyrrole in the presence of hydrochloric acid (3). Since then
various methods have been developed to increase the yield
and selectivity of the products (4–6). The disadvantages of
these methods are that the acid catalysts are corrosive in na-
ture and the workup procedure is tedious and it involves
neutralization. Moreover, the yields of calix[4]pyrrole are
low and they are accompanied by a mixture of linear oligo-
mers. There is a need to develop a method for the synthesis
of calix[4]pyrroles that is ecofriendly, economic, and
noncorrosive.
To meet the increasing demands of environmental legisla-
tion for the development of organic reactions in environmen-
tally friendly media, synthetic manipulations have to be
made to minimize the use of hazardous chemicals, such as
replacing the traditional organic solvents in reactions and
their subsequent workup with nontoxic solvents. In this re-
gard, ionic liquids, especially those based on 1,3-
dialkylimidazolium cations (Fig. 1), have gained consider-
able interest as a green alternative to volatile organic sol-
vents (VOS) in recent years (7). Their nonvolatile nature and
lack of any detectable vapour pressure gives them a signifi-
cant advantage in minimizing solvent consumption and also
addresses the problem of the emission of VOS into the at-
mosphere, thus making these solvents an environmentally at-
tractive alternative to classical organic solvents (8). The
recoverability and reusability of the catalysts immobilized in
ionic liquids are key features required to develop economi-
cal, efficient, and green chemical processes (9).
Lanthanide(III) trifluromethanesulfonates, Ln(OTf)3, have
enjoyed extensive applications in a variety of Lewis acid cat-
alyzed organic reactions (10). The growing interest in the use
of these salts is due to their ease of handling, noncorrosiveness,
reusability, and unique reactivity and selectivity. Ytterbium(III)
tris-trifluromethanesulfonate, Yb(OTf)3 (commonly called yt-
terbium triflate), is known to be a useful mild Lewis acid
and has gained importance in organic synthesis in recent
years (11). It was first used by Forsberg et al. (12) and since
then it has found a wide utility in organic synthesis (13).
Lanthanide triflates immobilized in ionic liquids have been
used as efficient and recyclable catalysts for different or-
ganic reactions. The chemistry of lanthanides and actinides
in ionic liquids was recently reviewed by K. Binnemans
(14).
Received 21 April 2008. Accepted 20 June 2008. Published
on the NRC Research Press Web site at canjchem.nrc.ca on
31 July 2008.
As a part of our ongoing research, we became interested
in ionic liquids as an alternative reaction media for various
organic transformations (15). We also reported Yb(OTf)3
catalyzed synthesis of 1,3-oxathiolanes in ionic liquids (16).
Herein, we report for the first time the synthesis of
calix[4]pyrroles catalyzed by Yb(OTf)3 in ionic liquids
A. Kumar,1 I. Ahmad, and M.S. Rao. Department of
Chemistry, Birla Institute of Technology and Science, Pilani
333 031, Rajasthan, India.
1Corresponding author (e-mail: anilkadian@gmail.com).
Can. J. Chem. 86: 899–902 (2008)
doi:10.1139/V08-121
© 2008 NRC Canada

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Can. J. Chem. Vol. 86, 2008
Scheme 1. Synthesis of calix[4]pyrroles in ionic liquid.
showed good reactivity and yield even after five cycles with
little deterioration in catalytic activity as shown in Table 2.
The slight deterioration in catalytic activity may be due to a
slight decomposition of the ionic liquids because of the re-
lease of water in the reaction. Generally, ionic liquids based
on imidazolium cation with either tetrafluoroborate or
hexafluorophosphate as anions are water insensitive; how-
ever, the exposure to moisture for a long time can cause
some changes in their physical and chemical properties (17).
The products obtained were of the same purity as in the first
reaction.
(Scheme 1), which is superior to previous Brønsted and
Lewis acid catalyzed methods and overcomes the problems
encountered with classical Lewis acids.
Conclusion
In conclusion, we have developed an efficient, simple,
economical, noncorrosive, and ecofriendly method for the
synthesis of various calix[4]pyrroles catalyzed by ytter-
bium(III) triflate in ionic liquids. This method provides sev-
eral advantages such as easy synthesis, simple workup, and
satisfactory recovery and reuse of the ionic liquid immobi-
lized ytterbium triflate with no diminution of product yields.
Results and discussion
The cyclocondensation of acetone (1) and pyrrole (10) at
room temperature in ionic liquid [bmim][BF4] containing 20
mol% Yb(OTf)3 gave 100% conversion of acetone after 10 h
as monitored by GC analysis. After completion of the reac-
tion, the product was extracted with an ethyl acetate ! hex-
ane mixture and purified by column chromatography to give
pure meso-octamethyl calix[4]pyrrole (11) in 92% yield (Ta-
ble 1, entry 1). The 1H NMR spectrum of 11 showed a broad
singlet at δ 9.23 for NH protons and a singlet at δ 5.67 and δ
1.50 for 8 β-pyrrolic protons and 24 meso-methyl protons,
respectively. It showed a [M + H]+ ion peak at m/z 429.2360
in the positive ion mode HRMS (ESI-MS) spectrum. In the
IR spectra of 11, a peak appeared at 3438 cm–1 for N!H
stretching.
Experimental section
All the chemicals and reagents were of analytical grade.
Ketones and pyrrole were purchased form S.D. Fine and
Spectrochem, India. Sodium tetrafluoroborate and 1-
methylimidazole were purchased from Sigma-Aldrich. Ionic
liquid [bmim][BF4] was prepared according to an earlier re-
1
ported procedure (15a, 15b). The H NMR spectra were re-
The reaction was also carried out in a more hydrophobic
ionic liquid, [bmim][PF6], and an almost equal yield of
calix[4]pyrrole (11) was obtained under these conditions.
Therefore, we chose [bmim][BF4] as the solvent of choice
for further reactions. After the success of this reaction, the
synthesis of meso-substituted calix[4]pyrroles (12–19) was
also studied by the condensation of different cyclic and acy-
clic ketones with pyrrole catalyzed by Yb(OTf)3 in ionic
liquid and the results are shown in Table 1. The products
corded on
a
Bruker Avance II 400 (400 MHz)
spectrophotometer using TMS as internal standard and
CDCl3 as solvent, and the chemical shifts were expressed in
ppm. The IR spectra were recorded using KBr pellets on a
Shimadzu Prestige-21 FTIR spectrophotometer and νmax was
expressed in cm–1. Mass spectra were recorded on a KC455
Waters TOF MS spectrometer. TLC was run on silica gel
coated aluminium sheets (silica gel 60 F254, E. Merck, Ger-
many) and visualized in UV light at 254 nm.
1
were characterized by IR, HR-MS, and H NMR spectros-
copy. Higher cyclic ketones and substituted acyclic ketones
produced slightly less yields as compared with acetone (Ta-
ble 1). The reaction of unsymmetrical ketones produced a
mixture of isomers, but αααα-isomer was in the majority.
We did not observe the formation of N-confused
calix[4]pyrroles under these conditions, which are reported
to be accompanied in minor amounts, along with
calix[4]pyrrole in a recently reported amberlyst 15 catalyzed
synthesis of calix[4]pyrroles (6d).
To study the reusability, the recovered ionic liquid con-
taining Yb(OTf)3 was reused for the synthesis of 16. After
extraction of calix[4]pyrrole from the ionic liquid with an
ethyl acetate ! hexane mixture, the ionic liquid containing
Yb(OTf)3 was dried under vacuum for 30 min. To this dried
ionic liquid containing Yb(OTf)3, pyrrole and acetophenone
(6) were added and stirred at room temperature for 12 h. The
reaction mixture was extracted by the ethyl acetate ! hexane
mixture and the combined organic layer was evaporated to
give 16. This cycle was repeated five times. The catalysts
General procedure for the synthesis of calix[4]pyrrole
in ionic liquid catalyzed by Yb(OTf)3
To a 10 mL round bottom flask containing ionic liquid
[bmim][BF4] (3.0 mL) was added acetone (110 µL, 1.49
mmol), freshly distilled pyrrole (103 µL, 1.49 mmol), and
Yb(OTf)3 (20 mol%, 46.2 mg). The reaction mixture was
stirred at room temperature for 10 h. Twenty microlitres of
the reaction mixture were removed after every 1 h interval
and analyzed by TLC and GC. After completion of the reac-
tion, the reaction mixture was extracted with hexane ! ethyl
acetate (2 × 5 mL, 1:1 v/v). Ionic liquid containing ytterbium
triflate was recovered and dried under vacuum. The com-
bined organic layer was evaporated under reduced pressure.
The residue was column chromatographed over silica gel
60–120 mesh using hexane ! ethyl acetate as eluent to give
pure 11 (146 mg, 92%). The calix[4]pyrrole obtained was
1
characterized by IR, H NMR, 13C NMR, and HRMS spec-
troscopic data.
© 2008 NRC Canada

Kumar et al.
901
Table 1. Synthesis of calix[4]pyrroles from different ketones catalyzed by 20 mol%
Yb(OTf)3 in ionic liquids
Entry
Ketone
Product
Time (h)
Conversion (%)a,b
1
2
3
4
5
6
7
8
9
R1 = R2 = CH3
R1 = C(CH3)3, R2 = CH3
R1-R2 = -(CH2)4-
R1-R2 = -(CH2)5-
R1-R2 = -(CH2)7-
R1 = Ph, R2 = CH3
R1 = 4-Me-Ph, R2 = CH3
R1 = 4-Cl-Ph, R2 = CH3
R1 = 3-NO2-Ph, R2 = CH3
11
12
13
14
15
16
17
18
19
10
10
10
10
12
12
12
15
15
100 (92)
98 (84)
99 (88)
95 (85)
93 (79)
97 (85)
98 (84)
95 (78)
96 (75)
aThe isolated yield provided by column chromatography on silca gel is in parentheses.
1
bAll products were characterized by IR, ESI-MS, H NMR, and 13C NMR spectra.
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Acknowledgements
This work was supported by the Department of Science
and Technology, New Delhi (SR-FTP-CS-34-2007). IA is
thankful to the Birla Institute of Technology and Science,
Pilani, for an institutional research fellowship.
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