Organic Halogen Binding Crowns: mesooctamethylcalix [4] pyrrole

Jenny Jiou

ABSTRACT:
Meso-octamethylcalix
[4]
pyrrole was synthesized and yielded
46.34%.
The
pure
compound
was
subjected to IR, NMR and UV-Vis
characterization. Conformational changes
were confirmed via NMR by adding
fluoride, while the colorimetric studies
were conducted in UV-Vis with 4nitrophenolate and fluoride ions.

INTRODUCTION

Figure1:Calix[4]pyrroleinunbound(A)andanionbound(B)
conformation.3

The foundation of supramolecular

chemistry was inspired by natures
phenomenon of non-covalent bonding
forces and protein-substrate interactions. 1
In time, chemists apply these principle to
organic synthetic systems. The innovation
came in the 1960s with the synthesis of
the crown ethers by Charles J. Pedersen.
After his discovery, other researchers such
as Donald J. Cram, Jean-Marie Lehn and
Fritz Vogtle became active in synthesizing
organic molecule cages that were either
anion and cation receptors. The research
in this new area proliferated with concepts
such
as
mechanically
interlocked
molecular architectures. The field of
supramolecular chemistrys importance
was formally recognized by the 1987 Nobel
Prize for Chemistry which was awarded to
Donald J. Cram, Jean-Marie Lehn, and
Charles J. Pedersen in recognition of their
work.2 The advance of selective "hostguest" complexes in particular, in which a
host molecule recognizes and selectively
binds a certain guest, was cited as an
important contribution. Supramolecular
Chemistry
overall
encompasses
the
interactions between molecules: how they
can distinguish each other, assemble and
function on a molecular scale.

In this particular instance, mesooctamethylcalix [4] pyrroles (calix [4]

pyrrole or calixpyrrole) are able to bind to
anions,
specifically
halogens.
X-ray
crystallographic
studies
showed
calixpyrrole has distinct conformational
changes when bound and unbound to an
anion (Figure 1).3 These changes can be
observed via NMR by the chemical shifts
difference before and after the addition of
fluoride. Not only is calixpyrrole a
macrocycle that binds to anions it also
contains colorimetric sensing capabilities
that is detectable by the naked eye. 4 This
property was further investigated with a
UV-Vis spectroscopy for its selectivity for
specific anions, like fluoride and 4nitrophenolate.
MATERIALS AND METHODS

Scheme1:Thereactionofcalix[4]pyrrole.

The following procedure was obtained

5
from
Shriver
et
al.
Mesooctamethylcalix[4]pyrrole was synthesized
in the following experiment by an acid
catalyzed reaction of pyrrole and acetone
(Scheme 1). To begin the reaction, 5 mL of
methanol (Fisher) was measured in a
graduated cylinder and added into a 125
mL Erlenmeyer flask. With a 1 mL syringe,
0.35 mL of pyrrole (5.0 mmol, Sigma
Aldrich) and 0.37 mL of acetone (5.0
mmol, Fisher) was added to the reaction
vessel and gently swirled to allow mixing.
Then two drops of sulfuric acid (Fisher) was
added using a Pasteur pipet to start the
reaction. Yellow-orange precipitate is
immediately observed where the drops
landed. The flask was gently swirled once
more to ensure even mixing of the
reaction. This reaction then was left to
stand for 30 minutes to ensure the
formation of pale yellow precipitate. After

letting the reaction sit, the reaction vessel

was subjected to an ice bath to force
precipitation of calix [4] pyrrole. The
precipitate was filtered on a Hirsh funnel
and washed three times with cold
methanol. A portion of the crude was
saved for Thin Layer Chromatography, and
the rest was subjected to purification by
recrystallization.
After the crude has dried, it was then
placed into a 100 mL beaker to begin the
recrystallization process. Acetone was then
added with slight heating until the solution
was saturated. Once dissolved, 3 mL of
water was added slowly with constant
mixing and heating. A white cloudy
precipitate is formed in the aqueous layer.
The beaker is then removed from heat and
left to stand for 10 minutes, followed by
cooling in an ice bath for 30 minutes. After
cooling in an ice bath, there should be the
formation of white crystals. Then filter
again using a Hirsh funnel and 3 mL of ice
cold methanol to wash. The crystals were
collected onto a watch glass to dry. The
mass obtained was 0.2483 g (0.5793
mmol) which gave a yield of 46.34%.
Calix [4] pyrrole was characterized
using NMR (270 MHz Jeol NMR), IR (Avatar
360 FT-IR), and UV-Vis Spectroscopy
(Shimadzu UV-160). The NMR was taken in
deuterated chloroform, and the spectral
shifts were analyzed when 0.1 mL of
tetrabutylammonium fluoride was added
to the NMR tube. The IR spectra was taken
using a KBr( (Sigma Aldrich) salt as a
background. KBr and calix [4] pyrrole were
mixed into a fine powder and pressed into
a IR solid sample holder. For the anion
binding characterization in UV-Vis, the
following solutions were made by Quang
To. In a 100 mL volumetric flask, 0.123 g of
tetrabutylammonium
4-nitrophenolate
(TBAPhO,
Acros)
was
diluted
in
dichloromethane (DCM, Fisher). Then
another 1:100 dilution was performed to
yield 3.6 x 10-6 M solution. In another 100
mL
volumetric
flask,
0.418
g
of
tetrabutylammonium
fluoride
(TBAF,
Sigma Aldrich) was measured and diluted
to 1.6 x 10-2 M solution. A quartz cuvette

was utilized because the solvent used to

analyze
calix
[4]
pyrrole
was
dichloromethane (Fisher). Approximately
10 mg of calix [4] pyrrole was diluted into
20 mL of DCM. Then 3 mL of this solution
was added into a quartz cuvette. A blank
of DCM was taken prior to sample analysis.
To observe peak shifts from the anions 0.6
mL of the TBAPhO solution was added and
analyzed. Then 0.6 mL of TBAF solution
was added into the same cuvette and
analyzed.
RESULTS AND DISCUSSION

TLC was performed on both the crude

and purified calix [4] pyrrole to assess the
level of purification for this particular
recrystallization.
The
products
were
spotted on a normal phase silica gel TLC
plate in a solvent system of 7:3
hexanes:ethyl
acetate.
The
crude
separated into two distinguishable spots
where as the recrystallized product
traveled as one spot (Figure 2).

Figure2:ThinLayerChromatographyofthecrudeand
recrystallizedcalix[4]pyrroleinpetroleumetherandethyl
acetate(7:3).

When comparing the literature, Shiver et al 5 also

notedtwo spots from the crude. The Rf values are
verysimilarforboththeimpurityandproduct,(Rf=
0.39and0.79respectively).Calix[4]pyrrolemoved
thegreatestdistancesinceitismorenonpolarthanthe
impurity which is likely a Nconfused calixpyrrole
whereoneofthefourpyrroleshasattachedatthe
position. The disrupted symmetry leads to more
exposedpolargroupsonthecompoundthustravels
slowerontheplate.
When characterizing calix [4] pyrrole for its anion
binding and colormetric properties the following

graph was produced (Figure 3). With only

calixpyrroleandDCMinthequartzcuvette,asmall
peakwasobservedat407.5nm.Withtheadditionof
0.5mLof3.6x106MofTBAPhO(yellowsolution)
was added into the cuvette the solution remained
clear.Finally,when1.6x10 2 MTBAFwasadded
into the cuvette, the yellow color reappeared. This
disappearanceandreappearanceofcolorgiveinsight
tocalixpyrrolespreferenceinbinding.

at 1415.8 cm1 is due to the pyrrole group on the

compound(Figure4).

Figure4:InfraredSpectraofcalix[4]pyrroleinKBr.

Figure3:UVVisspectrumofcalix[4]pyrroleandanionbinding
toTBAPhOandTBAF.

Calixpyrrole is a selective towards binding to

anions. The moment calixpyrrole binds to the
nitrophenolateion,theyellowcolordisappearswhich
correspondstothepeakdisappearanceinthe400nm
region.Sincecalixpyrrolehasahigherpreferencefor
halogens compared to the nitrophenolate ion, when
TBAFwasaddedintothemixture,thenitrophenolate
wasreplacedbyfluorideinthecalixpyrrolebinding
pocket. Then with the nitrophenolate back an
absorptionat430nmcorrespondstoavisiblewarm
yellowsolution.

The NMR spectrum collected for calixpyrrole

withoutTBAFagreedwithdatafromChauhanetal. 6
A sharp singlet at 1.51 ppm with an integration of
24.35representstheeightmethylgroups.Adoubletis
presentaround5.90ppmwithanintegrationcloseto
8whichaccuratelycharacterizesthehydrogensoffthe
sp2 carbonsonthepyrrole.Lastly,thebroadpeakat
7.04ppmintegratedto3.55ispresentduetothefour
hydrogens bonded to the nitrogen on the pyrrole
group(Table2).

Table1:TheIRpeaksforcalixpyrroleandstretches

IR spectroscopy was also performed on

calixpyrrrole.TheIRspectrumcontainedpeaksthat
agreeswiththebondspresentincalixpyrrole(Table
1).Thesp2carbonhydrogenstretchescaneasilybe
distinguished from the sp3 carbon hydrogen
stretches.Thenotablenitrogenhydrogenstretchat
3444.2cm1andcarboncarbondoublebondstretch

Figure 5: NMR spectra of unbound (top) and anion bound

(bottom)calix[4]pyrroleinCDCl3.

WhentheNMRofcalixpyrrolewasthentakenin
thepresenceofTBAF,therewereapparentshiftsfor
the methyl groups protons and the protons on the
pyrroles carbons. The methyl groups are more
deshieldedduetotheconformationalchangemaking
the methyl groups closer to the nitrogen and the

anion.Whiletheprotonsonthesp2carbonsaremore
shielded due to its orientation. Lastly the
disappearanceofthepeakfortheprotonbondedto
thenitrogenisduetothehydrogenbondingandanion
interactions. Before TBAF, the pyrrole groups are
alternating, so the methyl groups are pointed away
fromthenitrogenandthesp 2 carbonsarecloserto
neighboring nitrogen making, making them more
deshielded. When a fluoride ion is bound to
calixpyrrole, the conformational changes causes all
the nitrogen to point towards the fluoride for
hydrogen bonding stability. Then the flip in
alternatingpyrrolegroupscausesthesp 2 carbonsto
faceeachothermakingthepeakshiftupfield.
Table2:ListofpeaksofinterestonCalixpyrrolebeforeandafter
theadditionofTBAF.

of pyrrole with acetone successfully. Following the

synthesisandpurification,itsanionbindingproperties
wereanalyzedusingNMRandUVVisspectroscopy
anditwasfurthercharacterizedbyIRspectroscopy..
It was observed that calix[4]pyrrole is a selective
anionbinder.Whenboundtheanion,thecompound
goesthroughaconformationalchangenotedbyshifts
intheNMR.UnderUVVis,calix[4]pyrrolewasina
solutionwithfluorideandnitrophenolateanions,and
it selectively bonded to the fluoride. Thus making
derivativesofthisparticularcompoundofinterestto
observeotherionbindingabilities.
REFERENCES
[1] The Supramolecular Chemistry Of Life.
Supramolecular Chemistry. 49104.
[2] Nobel Prize In Chemistry: Jean-Marie Lehn with
Donald J. Cram and Charles J. Pedersen in 1987. lettre-cdf.
2015, 11.
[3] Gale, P. A.; Sessler, J. L.; Krl, V.; Lynch, V.
Calix[4]Pyrroles: Old Yet New Anion-Binding Agents. J.
Am. Chem. 1996, 118, 51405141.
[4] Fluorine and the Environment. Agrochemicals,
Archaeology, Green Chemistry & Water, 81-86.
[5] Shriver, J. A.; Westphal, S. G. Calix[4]Pyrrole:
Synthesis and Anion-Binding Properties. An Organic
Chemistry Laboratory Experiment. J. Chem. Educ. Journal
of Chemical Education. 2006, 83, 1330.
[6] Chauhan, S. M. S.; Garg, B.; Bisht, T. Syntheses Of
Calix[4]Pyrroles by Amberlyst-15 Catalyzed
Cyclocondensations of Pyrrole with Selected Ketones.
Molecules. 2007, 12, 24582466.

CONCLUSIONS

Mesooctamethylcalix[4]pyrrolewassynthesized
inthisexperimentbysulfuricacidcatalyzedreaction