Tri- and pentacalix[4]pyrroles: Synthesis, characterization and their use in the extraction of halide salts

Article abstract of DOI:10.1002/chem.201101605

Calixpyrrole-based oligomeric compounds were synthesized by "click chemistry" from the corresponding alkyne- and azide-functionalized calix[4]pyrroles. Calix[4]pyrrole 3, possessing an alkyne functional group, was prepared through a mixed condensation of

Full text of DOI:10.1002/chem.201101605

FULL PAPER
DOI: 10.1002/chem.201101605
Tri- and Pentacalix[4]pyrroles: Synthesis, Characterization and Their Use in
the Extraction of Halide Salts
Abdullah Aydogan* and Ahmet Akar*[a]
Abstract: Calixpyrrole-based oligomer-
ic compounds were synthesized by
“click chemistry” from the correspond-
ing alkyne- and azide-functionalized
calix[4]pyrroles. Calix[4]pyrrole 3, pos-
sessing an alkyne functional group, was
prepared through a mixed condensa-
tion of pyrrole with acetone and but-3-
ynyl 4-oxopentanoate. Another alkyne-
group-containing calix[4]pyrrole 5 was
obtained by treatment of 4’-hydroxy-
phenyl-functionalized calixpyrrole
4
through a condensation reaction of pyr-
role and 7-bromohept-2-one. Oligomer-
ic calixpyrrole compounds were found
to be capable of extracting tetrabuty-
lammonium chloride and fluoride salts
from aqueous media. Extraction abili-
ties of the oligomeric compounds were
monitored by NMR and UV/Vis spec-
troscopy and thermogravimetric analy-
sis.
with propargyl bromide. Tetrakis(azi-
dopentyl)-functionalized calix[4]pyrrole
7 was synthesized by reacting NaN3
with
tetrabromopentyltetraethylca-
lix[4]pyrrole 6, which was prepared
Keywords: calix[4]pyrroles
· click
chemistry · extractants · halides ·
oligomers
Introduction
ular interest,[8] because the core structure can be accessed in
one synthetic step and a large number of modifications are
readily conceivable. To date, simple meso-alkyl-substituted,
halogenated,[10] C-rim modified,[11] photoactive and chromo-
phore-modified,[5] strapped,[12] ditopic,[13] expanded,[14] N-
confused,[15] siloxane-functionalized,[16] and polyfunctional[17]
calixpyrrole derivatives have been reported.
The area of anion recognition represents an evolving area of
supramolecular chemistry and its impact in such disparate
areas as environmental chemistry[1] and biomedicine[2] is be-
coming increasingly valued. Anions play crucial roles in reg-
ulating human health[3] and are ubiquitous in biological sys-
tems.[4] In addition, anion receptors can be used as ion-selec-
tive receptors,[5] phase-transfer catalysts, and anion-selective
optical sensors.[6] Their particular importance in the nuclear
fuel cycle is also well recognized.[7] Moreover, chromato-
graphic separation systems have been generated by attach-
ing receptors to an appropriate stationary phase.[8] These
and other practical considerations have led to a spectacular
growth within the anion-recognition field. However, the
weak nature of most anion–receptor interactions, particular-
ly in the case of neutral-anion-receptor systems that reflect
the relatively low-charge density of most anions,[9] makes
the design of selective and effective receptors an on-going
challenge. Thus, while a number of research groups have de-
signed elegant anion receptors, many of which have proven
to be quite effective, there still remains a need for simple
and easy-to-make anion-binding systems. In this context, cal-
ix[4]pyrroles, which are macrocyclic compounds containing
four pyrrole units connected to each other through sp3-hy-
bridized carbon atoms, have emerged as molecules of partic-
Calix[4]pyrroles have also engendered extensive research
effort because of their ability to recognize certain anionic
guests (e.g., fluoride, chloride, and dihydrogen phosphate)
in organic media.[18] The nature of the binding interactions
of these macrocyclic compounds involves hydrogen bonding,
which leads to the general expectation that in highly com-
petitive media calixpyrroles would display substantially re-
duced anion affinities.[19] However, recent reports in which
calixpyrroles are either covalently attached to solid supports
to produce anion-selective HPLC packings[20] or are embed-
ded in several functional materials, for example, colorimetric
sensors[21] and ion-selective electrodes,[22] showed that cal-
ix[4]pyrroles and its derivatives can be used as highly effec-
tive anion receptors under mixed organic–aqueous interfa-
cial conditions. Particular interest is devoted to calixpyrroles
attached to PMMA-based polymeric backbones (PMMA=
poly(methyl methacrylate)) with an increased number of re-
ceptor sites to enable the extraction of halide salts (e.g., tet-
rabutylammonium and potassium salts of fluoride and chlo-
ride) selectively from aqueous solutions.[23] Although poly-
meric structures can be used as effective extractants for the
specific anions that calixpyrroles can bind selectively, well-
defined oligomeric structures, constructed at the meso-posi-
tions of calix[4]pyrrole cores by taking advantage of click
chemistry, can be used as effective linear polymeric ana-
logues. These findings prompted us to consider that soluble
oligomeric materials, based on calix[4]pyrrole cores linked
[a] Dr. A. Aydogan, A. Akar
Istanbul Technical University, Department of Chemistry
Maslak 34469 Istanbul (Turkey)
E-mail: aydoganab@itu.edu.tr
akara@itu.edu.tr
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201101605.
Chem. Eur. J. 2012, 18, 1999 – 2005
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1999

directly to each other through triazole rings, could also be
capable of extracting anions from their aqueous solutions.
Such materials, based on calix[4]pyrroles, may find utility in
addressing a variety of current challenges, including corro-
sion prevention (e.g., chloride, carbonate, and sulfate con-
trol under conditions of combustion[24]) and waste remedia-
tion (e.g., sulfate extraction from tank waste[25]).
Herein, we report the synthesis and characterization of
tri- and pentacalix[4]pyrrole precursors, that is, ketone 1
containing an alkyne functional group, calix[4]pyrroles 3
and 5, compound 7, with four azide units connected to the
meso-positions of the calix[4]pyrrole-core structure, and oli-
gomeric calix[4]pyrroles 8–11, synthesized by click chemis-
try. In addition, we demonstrate that organic solutions of
the pentacalix[4]pyrroles are capable of extracting tetrabuty-
lammonium chloride (TBACl) and tetrabutylammonium
fluoride (TBAF) from aqueous solutions more effectively
reacting propargyl bromide with 4-hydroxyphenyl-function-
alized calixpyrrole derivative 4, which was obtained through
a mixed condensation reaction of pyrrole with acetone and
4-hydroxyacetophenone. Tetrabromo-functionalized calix[4]-
pyrrole 6 was synthesized by an acid-catalyzed condensation
of pyrrole and 7-bromoheptan-2-one[26] in MeOH. The re-
sulting calix[4]pyrrole 6 was then quantitatively converted
to its corresponding tetraazido derivate 7 in the presence of
NaN3 in DMF at room temperature.
Click reactions, named by Sharpless and co-workers, can
be characterized as reactions displaying high yields, compati-
bility with a large scale of functional groups, tolerance to a
variety of solvents, and mild reaction conditions.[27] Gale and
co-workers reported the synthesis of bis-1,2,3-triazole-strap-
ped calix[4]pyrroles through click chemistry.[28] The synthesis
of calix[4]pyrrole-based oligomeric compounds was achieved
by click reactions, inspired from Sharplessꢁ and Galeꢁs re-
ports. To obtain the desired oligomeric structures, tetraazi-
do-functionalized calixpyrrole 7 was dissolved in THF and
reacted with calixpyrrole 3 or 5 in the presence of an aque-
ous solution of sodium ascorbate and CuSO4·5H2O at room
temperature (Scheme 2). After 48 h, the crude products
were extracted with CH2Cl2 and precipitated from hexane
after workup. Tricalix[4]pyrroles 10 and 11 were prepared in
an analogous manner. In this case, the alkyne-functionalized
calixpyrrole compounds 3 and 5 were treated with 1,3,5-tri-
s(azidomethyl)benzene[29] (12) to synthesize the desired tri-
podal oligomeric calix[4]pyrroles.
than calixpyrrole
2 and tricalix[4]pyrroles 10 and 11
(Schemes 1 and 2). To the best of our knowledge, this is the
first example of calixpyrrole receptors constructed to well-
defined oligomeric structures and the first report wherein
calix[4]pyrrole-receptor-based oligomeric systems of any
type have been used to effect anion extraction under inter-
facial aqueous–organic conditions.
Results and Discussion
The alkyne-functionalized calix[4]pyrrole 3 was prepared in
17% yield through a mixed condensation reaction of pyrrole
with 1 and acetone in MeOH using a catalytic amount of
methanesulfonic acid (Scheme 1). The second alkyne-func-
tionalized calix[4]pyrrole 5 was synthesized in 90% yield by
Scheme 1. Synthesis of alkyne- and azide-functionalized calix[4]pyrroles.
Scheme 2. Synthesis of star-shaped oligomeric calix[4]pyrrole compounds.
2000
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Chem. Eur. J. 2012, 18, 1999 – 2005

Tri- and Pentacalix[4]pyrroles
FULL PAPER
À
The compounds were characterized and the occurrence of
the click reactions was monitored by using FTIR and NMR
spectroscopy and corroborated by mass spectrometry. For
example, in the case of the H NMR analysis of compound
11, the extent of conversion of azido moieties to triazole
alkyne groups was evidenced by characteristic bands of H
À1
ꢀ
À
C C at n˜ =3234 cm for compound 3. Pyrrole N H stretch-
ing bands of compound 3 were observed at n˜ =3433 and
3367 cmÀ1, while the same stretching band belonging to
compound 10 was observed at n˜ =3421 cmÀ1. Compounds 6
and 7 were also subjected to FTIR spectroscopic analysis.
Figure 2 shows the actual conversion of tetrabromo-substi-
tuted calix[4]pyrrole 6 into its corresponding tetraazido-sub-
stituted derivative 7, based on the presence of a N3 stretch-
ing band at n˜ =2082 cmÀ1. These spectral characterizations
clearly support that the desired alkyne- and azide-function-
alized calix[4]pyrroles have been synthesized successfully.
The disappearance of the azide stretching band of com-
pound 10 at n˜ =2082 cmÀ1 after click reaction supports the
expected triazole-ring formation of the obtained oligomeric
calix[4]pyrrole compound 10. Similar results that indicate
the successful synthesis of oligomeric compounds were also
observed in the case of the compounds 8, 9, and 11 (see the
Supporting Information).
1
rings was monitored by observing the disappearance of the
À
N3 CH2 signal of compound 12 at d=4.39 ppm and the ap-
pearance of the CH protons of compound 11 belonging to
À ꢀ
the triazole ring at d=7.56 ppm. Additionally, CH2 C C
protons of the calix[4]pyrrole 5 showed an upfield shift from
d=4.65 to 5.15 ppm after the formation of the triazole ring
(Figure 1). Although all the oligomeric compounds have
Once the star-shaped oligomeric calix[4]pyrrole com-
pounds were fully characterized, efforts were directed to-
wards exploring their ability to bind anions under interfacial
conditions. Initial qualitative evidence that 8 and 9 could ex-
tract chloride salts into organic media came from a visual
test involving compound 13, a water-soluble dye that con-
tains a chloride counterion. Treatment of an aqueous solu-
tion of 13 (25.5 mm) with a solution of 8 (0.90 mm) and 9
(0.89 mm) in CH2Cl2 resulted in green organic phases
(Figure 3, see the Experimental Section for a detailed ex-
planation of the extraction process).
1
Figure 1. Partial H NMR spectra of the compounds 5, 11, and 12, record-
ed in CDCl3.
1
good solubility in common organic solvents, H NMR spec-
tra of some oligomers revealed relatively broadened peaks
(see the Supporting Information), reflecting the asymmetric
nature and high molecular weight of the oligomers.
The structures of both starting materials and oligomers
were also monitored by FTIR spectroscopy. Figure 2 shows
the results of the FTIR spectroscopic analysis of alkyne-
functionalized calix[4]pyrrole 3, tetraazide-functionalized
calix[4]pyrrole 7, and tri-calix[4]pyrrole 10. The presence of
Figure 3. Aqueous solutions of 13 (top layers): a) After treatment with
CH2Cl2 and after treatment with solutions of b) 2, c) 10, d) 11, e) 8, and
f) 9 in CH2Cl2 (bottom layers).
As control experiments, solutions of the dye were also ex-
posed to CH2Cl2 and solutions of 2 (6.23 mm), 10 (1.43 mm),
and 11 (1.42 mm) in CH2Cl2; however, the observed transfer
of color was not as intense as for 8 and 9. These results were
quantified by using UV/Vis spectroscopy (Figure 4). Analy-
sis of the aqueous phases of these extraction experiments
confirmed that 9 was able to extract 13 into the organic
phase more effectively than 2, 10, and 11 (greater than 56–
79%, see the Supporting Information for detailed extraction
data).
Encouraged by these initial results, we next sought to ad-
dress the question if the oligomers 9 and 10 (as model com-
Figure 2. FTIR spectra of the compounds a) 10, b) 3, and c) 7.
Chem. Eur. J. 2012, 18, 1999 – 2005
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A. Aydogan and A. Akar
A solution of the tripodal oligomer 10 (0.8 mm) in CH2Cl2
was also subjected to extraction of TBAF and TBACl under
the same conditions that were used for the compound 9. As
show in Figure 6, no TBAF extraction was observed when
Figure 4. UV/Vis spectra of aqueous solutions of 13 (initial concentra-
tion=25.5 mm) after exposure to an equal volume of a) a CH2Cl2 solution
and solutions of b) 2, c) 10, d) 11, e) 8, and f) 9 in CH2Cl2.
pounds) could extract TBA+ salts (for a detailed explana-
tion of the extraction process see the Experimental Section).
As shown in Figure 5, the addition of a solution of tetrabu-
Figure 6. 1H NMR spectra of a) oligomer 10 in CDCl3; b) after i) adding
a solution of TBAF in D2O (90 mm, 0.5 mL) to a solution of 10 in CD2Cl2
(0.8 mm), ii) shaking the tube vigorously, and iii) allowing the phases to
separate; and c) solution of 10 after being subjected to the same treat-
ment with TBACl, as applied in (b). *=residual solvent.
compound 10 was used as the extractant. Figure 6b indicates
the absence of peaks referable to the methylene units of the
TBA+ counterion, as well as no shift of the pyrrole NH res-
onances. However, in the case of TBACl, both the TBA+ as-
cribable peaks and the downfield shift of the pyrrole NH
resonances were observed. These results led us to conclude
that tripodal oligomer 10 can extract ClÀ ions into organic
media better than control compound 2. Another result that
can be concluded from Figures 5 and 6 is that the pentaca-
lix[4]pyrrole 9 extracts FÀ and ClÀ ions better than the trica-
lix[4]pyrrole 10 and the control compound 2, as judged from
the integration of the peaks referring to the methylene units
of the TBA+ counterions and the resonances of the b-pyr-
rolic CH protons. The enhanced extraction ability of penta-
calix[4]pyrrole 9 compared to tricalix[4]pyrrole 10 points
out a possible cooperative effect of the number of individual
calixpyrrole units present in the structure of 9.
Figure 5. 1H NMR spectra of solutions of a/b) oligomer 2 (29 mm) and d/
e) oligomer 9 (0.5 mm) in CD2Cl2 after i) adding a solution of TBAX in
D2O (90 mm, 0.5 mL), ii) shaking the tube vigorously, and iii) allowing
the phases to separate. c) Oligomer 9 in CDCl3. *=residual solvent.
The ability of the oligomers 9 and 10 to extract several
other TBA+ salts was also tested. While no extraction was
observed in the case of aqueous solutions of tetrabutylam-
monium dihydrogen phosphate, upon addition of TBACl
downfield shifts of the NH proton signals greater than those
observed with TBAF for analogous anion concentrations
were visible. Such findings, which are consistent with an en-
hanced ability to extract chloride relative to fluoride or di-
hydrogen phosphate, are in contrast to the relative anion af-
finities observed in CH2Cl2.[18a] However, they are in accord-
ance with the expectations based on the so-called Hofmeis-
ter bias,[30] namely, that a more hydrophobic anion, such as
chloride (DGh =À340 kJmolÀ1), is extracted more easily
than a highly hydrophilic species, such as dihydrogen phos-
tylammonium fluoride (TBAF, 90 mm) in D2O to a solution
of oligomer 9 (0.5 mm) in CD2Cl2 resulted in a substantial
downfield shift of the pyrrole NH protons (as typically seen
upon anion binding[18a]). In addition, peaks ascribable to the
methylene units in the TBA+ counter ion (at d=3.2 ppm)
were visible, supporting the notion that both the anion (FÀ)
and the cation were present in the organic phase. In con-
trast, no shifts in the NH resonances and no peaks ascriba-
ble to TBA+ were observed when a 29 mm solution of octa-
methylcalix[4]pyrrole (2) in CD2Cl2 was exposed to aqueous
solutions of TBAF.
phate
(DGh =À465 kJmolÀ1)
or
fluoride
(DGh =
À465 kJmolÀ1).[31] Consistent with this rationale is the find-
ing that the control calixpyrrole 2 was able to extract
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Tri- and Pentacalix[4]pyrroles
FULL PAPER
TBACl under the aforementioned interfacial conditions,
albeit with efficiencies of less than 50% relative to oligomer
9 (as calculated from NMR integrations of the b-pyrrolic
and TBA+ signals). On the other hand, the fact that effi-
cient extraction of TBAF was only seen in the case of oligo-
mer 9 (and not for compounds 2 and 10) underscores the
notion that the calixpyrrole receptors constructed to an oli-
gomeric backbone and the number of calix[4]pyrrole units
in the oligomers play a critical role, as judged from our pre-
vious studies.[23]
whereas a 30% mass loss (theoretical: 31%) was observed
in the case of TBACl. Considering the relative extraction
abilities of 9 and 10 towards TBACl and TBAF (see above),
the observed mass losses were considered reasonable.
Conclusion
In conclusion, we have demonstrated the synthesis of four
different oligomeric calix[4]pyrrole compounds in excellent
yields. The process involves the synthesis of azide-functional
core structures and subsequent click reaction of these com-
pounds with alkyne-functionalized calix[4]pyrroles. The
strategy that was used in this study is entirely satisfactory in
terms of efficiency and simplicity. This method is the first
example of click chemistry directly applied for the construc-
tion of star-shaped oligomeric calix[4]pyrrole compounds.
Furthermore, these oligomeric calix[4]pyrrole compounds
were used in the extraction of FÀ and ClÀ salts of tetrabuty-
lammonium cations. Extraction experiments revealed that,
while pentacalix[4]pyrrole derivatives 8 and 9 were extract-
ing fluoride and chloride ions into the organic phase, trica-
lix[4]pyrrole derivatives 10 and 11 were just able to extract
chloride ions. Another major conclusion is that these oligo-
meric calixpyrrole compounds are as effective and selective
as polymeric analogues of this class of macrocycles. Detailed
investigations of binding stoichiometries, affinity constants
of the compounds, and of exploring the possible cooperative
effects of calix[4]pyrrole units in the extraction of specific
anions are underway.
Further support for the suggestion that oligomers 9 and
10 could extract fluoride and chloride ions was based on
thermal analyses. As shown in Figure 7, after independently
Figure 7. Partial thermogravigrams of oligomers 9 (left) and 10 (right) a)
before and after treatment with b) TBAF or c) TBACl.
exposing TBAF or TBACl to a solution of 9 in CH2Cl2, as
described above, organic layers of these samples were sub-
jected to thermogravimetric analysis. For this purpose
CH2Cl2 was removed after the extraction experiment and
the remaining solid was dried for 24 h under reduced pres-
sure.
As can be judged from Table 1, for the sample of 9 ex-
posed to TBAF an 8% mass loss was observed upon heating
to 2908C. This is low in comparison to the theoretical mass
Experimental Section
General considerations: All solvents were dried before use according to
standard literature procedures. Unless specifically indicated, all other
chemicals and reagents used in this study were purchased from commer-
cial sources and used as received. 1H and 13C NMR spectra used for the
characterization of products were recorded on Varian Unity 300 or
400 MHz and Bruker 250 MHz AC-3000 spectrometers using a residual
solvent as the reference. Low-resolution FAB and CI mass spectra were
obtained on a Finningan MAT TSQ 70 mass spectrometer. High-resolu-
tion FAB and CI mass spectra were obtained on a VG ZAB2-E mass
spectrometer. UV/Vis measurements were studied on a Bio HITACHI
U-0080D spectrometer. Thermogravimetric analyses were carried out by
using a TA, TGA Q50 instrument in a flowing nitrogen atmosphere at a
Table 1. Mass losses of the dried organic layers after extraction.[a]
Compound
TBAF [%][b]
TBACl [%][b]
9
10
8
<1
32
30
[a] Obtained from TGA (TGA=thermogravimetric analysis). [b] Percen-
tages were calculated after subtracting the mass losses of the pure com-
pounds upon heating to 2908C.
heating rate of 208CminÀ1
.
Extraction of TBA+ salts: In a tube an aqueous solution of the desired
TBA+ salt was added to a solution of the sample in CD2Cl2 (in the case
of UV/Vis analysis the solvent was CH2Cl2). The resulting mixture was
shaken vigorously until an emulsion was obtained. The organic and aque-
ous layers were separated clearly within 5 min with the aid of centrifuga-
tion at 4000 rpm. These two layers were subjected individually to UV/
Vis, NMR, or thermogravimetric analyses.
loss of 34.5%, assuming that the TBAF became completely
volatile over the aforementioned temperature range and
was present in less than a 1:1 stoichiometry relative to each
calix[4]pyrrole unit in the oligomer. In contrast, the sample
of 9 exposed to TBACl exhibited a 32% mass loss (theoreti-
cal: 31.7%) upon heating to 2908C. For comparison, trica-
lix[4]pyrrole 10 was also subjected to thermogravimetric
analysis after exposure to TBACl and TBAF under the
same conditions applied for 9. In the case of TBAF no rea-
sonable mass loss was observed upon heating to 2908C,
But-3-ynyl 4-oxopentanoate (1): Levulinic acid (3 g, 25.8 mmol), 3-butyn-
1-ol (1.75 mL, 23.48 mmol), and DMAP (32 mg, 0.26 mmol) were dis-
solved in CH2Cl2 (30 mL) and DCC (5.32 g, 25.8 mmol) was added. The
reaction mixture was stirred for 24 h at room temperature and the insolu-
ble matter was filtrated off. The resulting filtrate was collected and
washed with first 0.5n HCl (30 mL), followed by saturated NaHCO3
(30 mL), and then finally water (30 mL). The organic layer was then
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2003

A. Aydogan and A. Akar
dried over Na2SO4 and the solvent was removed under vacuum. Flash
column chromatography (silica gel, CH2Cl2) afforded the compound 1 as
a light yellow liquid (3.8 g, 96%). FTIR (ATR): n˜ =3281, 2964, 2916,
lowing this bubbling, methanesulfonic acid (1.18 mL, 18.1 mmol) was
added dropwise over the course of 10 min, while shielding the reaction
vessel from light. The mixture was then stirred at 08C for 3 h and subse-
quently at room temperature overnight. The white precipitate was col-
lected by filtration and washed with MeOH, yielding the calixpyrrole 6
as a white solid (4.9 g, 78.1%). FTIR (ATR): n˜ =3420, 2932, 2857, 1574,
1715, 1408, 1356, 1154, 1068, 1031, 1001 cmÀ1 1H NMR (250 MHz,
;
CDCl3): d=1.99 (t, J=2.4 Hz, 1H; CH), 2.18 (s, 3H; CH3), 2.51 (td, J=
2.4, 6.8 Hz, 2H; CH2), 2.59 (t, J=6.6 Hz,2H; CH2), 2.75 (t, J=6.3 Hz,
2H; CH2), 4.17 ppm (t, J=6.8 Hz, 2H; CH2); 13C NMR (75 MHz,
CDCl3): d=18.9, 27.9, 29.7, 37.9, 62.2, 69.9, 80.0, 172.4, 206.3 ppm;
LRMS (EI): m/z (%): 169.0 (100) [M+H]+; HRMS (ESI): m/z calcd for
C9H13O3 [M+H]+: 169.0865; found: 168.1236.
1501, 1414, 1247, 1193, 1037, 756, 711 cmÀ1 1H NMR (250 MHz, CDCl3):
;
d=1.01–1.14 (brm, 8H; CH2), 1.39–1.41 (brm, 20H; meso-CH3 CH2),
1.71–1.83 (brm, 16H; CH2), 3.35 (brt, J=6.75 Hz, 8H; CH2), 5.87–5.88
(m, 8H; pyrrole CH), 6.96 ppm (brs, 4H; NH); 13C NMR (75 MHz,
CDCl3): d=137.0, 103.8, 40.5, 38.8, 33.7, 32.7, 28.7, 26.6, 23.6 ppm;
LRMS (ESI): m/z (%): 963.05ACHTNUGRTNEUNG
(100) [M]À; HRMS (ESI): m/z calcd for
meso-Alkyne-functionalized calix[4]pyrrole (3): Pyrrole (3 mL,
43.2 mmol) and 1 (1.82 g, 10.8 mmol) were dissolved in MeOH (50 mL)
at 08C and bubbled with argon for 10 min. Acetone (2.38 mL,
32.4 mmol) was then added to the mixture. Following this addition, meth-
anesulfonic acid (1.97 mL) was added dropwise over the course of
10 min, while shielding the reaction vessel from light. The mixture was
then stirred at 08C for 3 h and subsequently at room temperature over-
night. The yellow precipitate that formed during this time was collected
by filtration. Chromatographic purification (silica gel, CH2Cl2/hexanes:
80/20) yielded the calixpyrrole 3 as a yellow solid (1 g, 17%). M.p.
>2008C (decomp); FTIR (ATR): n˜ =3421, 3363, 3231, 2968, 1730, 1576,
C44H63N4 [M]À: 963.1792; found: 963.1583.
Tetra-1-azido-tetramethylcalix[4]pyrrole (7): 6 (200 mg, 0.2 mmol) and
sodium azide (134.2 mg, 2 mmol) were dissolved in dry DMF (25 mL) at
room temperature and stirred for two days. After the reaction was com-
plete, DMF was removed under vacuum at 608C. The resulting crude ma-
terial was dissolved in CH2Cl2 and washed with water three times. The or-
ganic layer was dried over Na2SO4 and the solvent was removed under
vacuum, yielding the calixpyrrole 7 as a light yellow solid (166 mg,
98.4%). FTIR (ATR): n˜ =3415, 3358, 2968, 2858, 2086, 1680, 1572, 1453,
1415, 1396, 1244, 1038, 756, 711 cmÀ1 1H NMR (250 MHz, CDCl3): d=
;
1414, 1303, 1273, 1177, 1040, 759, 705 cmÀ1
;
1H NMR (250 MHz, CDCl3):
1.09–1.53 (brm, 36H; CH2, CH3), 1.76–1.83 (brm, 8H; CH2), 3.20 (t, J=
6.68 Hz, 8H CH2), 5.86–5.87 (m, 8H; pyrrole CH), 6.98 ppm (brs, 4H;
NH); 13C NMR (75 MHz, CDCl3): d=137.3, 103.8, 51.4, 40.6, 38.8, 28.9,
27.3, 26.4, 24.0 ppm; LRMS (FAB): m/z (%): 817 (100) [M+H]+; HRMS
(FAB): m/z calcd for C44H65N16 [M+H]+: 817.5573; found: 817.9816.
d=1.41–1.54 (brm, 21H; meso-CH3), 1.98 (t, J=2.5 Hz, 1H; CH), 2.15–
2.19 (brm, 4H; CH2), 2.46 (td, J=6.7, 2.5 Hz, 2H; CH2), 4.10 (t, J=
6.7 Hz, 2H; CH2), 5.88 (brs, 8H; pyrrole CH), 7.03 ppm (brs, 4H; pyr-
role NH); 13C NMR (126 MHz, CDCl3): d=173.1, 172.4, 137.8, 137.8,
137.5, 137.3, 135.2, 135.1, 103.2, 101.9, 101.9, 101.8, 79.1, 68.8, 61.0, 50.5,
50.5, 37.4, 34.2, 34.2, 34.2, 28.0, 24.9, 17.9 ppm; LRMS (ESI): m/z (%):
537.29 (100) [M]À; HRMS (ESI): m/z calcd for C34H41N4O2 [M]À:
537.3235; found: 537.4601.
Pentacalix[4]pyrrole (8): In a flask, 7 (50 mg, 61 mmol) and 3 (145.05 mg,
269.25 mmol) were dissolved in THF (50 mL). A freshly prepared aque-
ous solution of sodium ascorbate (106.7 mg, 0.54 mmol; 0.5 mL) was
added, followed by an aqueous solution of copper(II) sulfate pentahy-
drate (64.8 mg, 0.27 mmol; 0.5 mL). The ratio of the azide and alkyne
groups was 1:4. The mixture was stirred for two days at ambient tempera-
ture. THF was removed under vacuum and the remaining crude mixture
was dissolved in CH2Cl2 and washed with water three times. The organic
layer was then dried over Na2SO4 and the excess of solvent was removed
under vacuum. Precipitation from hexane afforded the compound 8 as a
white solid (181 mg, 95%). FTIR (ATR): n˜ =3423, 2965, 1730, 1575,
meso-4’-Hydroxyphenyl-functionalized calix[4]pyrrole (4): Pyrrole (6 mL,
86.7 mmol) and 4-hydroxyacetophenone (2.95 g, 21.7 mmol) were dis-
solved in MeOH (250 mL) at 08C and bubbled with argon for 10 min.
Acetone (4.78 mL, 65.1 mmol) was then added to the mixture. Following
this addition, methanesulfonic acid (4.22 mL) was added dropwise over
the course of 10 min, while shielding the reaction vessel from light. The
mixture was then stirred at 08C for 3 h and subsequently at room temper-
ature overnight. The white precipitate that formed during this time was
collected by filtration. Chromatographic purification (silica gel, CH2Cl2/
hexanes: 80/20, CH2Cl2/MeOH: 99/1) yielded the calixpyrrole 4 as a
1417, 1224, 1165, 1039, 764 cmÀ1
;
1H NMR (250 MHz, CDCl3): d=7.39–
À
7.03 (m, 24H; NH, CH), 5.87 (s, 40H; pyrrole-CH), 4.24 (m, 16H; N
À
CH2, O CH2), 2.96 (t, J=2.9 Hz, 8H; CH2), 2.15–1.40 ppm (m, 144H;
1
white solid (1,83 g, 16.6%). H NMR (400 MHz, CDCl3): d=7.18 (s, 2H;
CH3, CH2); 13C NMR (126 MHz, CDCl3): d=142.8, 137.9, 137.6, 137.4,
135.2, 103.1, 101.9, 101.8, 62.2, 49.2, 37.7, 37.4, 34.2, 34.2, 28.7, 28.2, 28.1,
25.9, 25.0, 24.4, 13.1 ppm; LRMS (ESI): m/z (%): 3002 (100) [M+H+
MeOH]+; HRMS (ESI): m/z calcd for C181H237N32O9 [M+H+MeOH]+:
3002.9066; found: 3002.7298;. elemental analysis calcd (%) for
C181H237N32O9: C 72.74, H 7.87, N 15.08, O 4.31; found: C 72.13, H 8.09,
N 14.71, O 4.87.
NH), 7.07 (s, 2H; NH), 6.86 (d, J=6.85 Hz, 2H; ArH), 6.66 (d, J=
6.85 Hz, 2H; ArH), 5.89 (s, 6H; pyrrole CH), 5.65 (s, 2H; pyrrole CH),
4.74 (s, 1H; OH), 1.83 (s, 3H; CH3), 1.54–1.49 ppm (m, 18H; CH3);
13C NMR (101 MHz, CDCl3): d=154.2, 139.0, 138.8, 138.7, 137.2, 128.8,
114.8, 105.9, 103.3, 103.0, 44.3, 35.5, 29.9, 28.9 ppm; LRMS (ESI): m/z
(%): 507 (100) [M+H]+; HRMS (ESI): m/z calcd for C33H38N4O [M]+:
506.3046; found: 506.2641.
Pentacalix[4]pyrrole (9): This compound was prepared by click reaction
of 7 (50 mg, 61.19 mmol) and 5 (146.7 mg, 269.25 mmol), using the same
procedure used to prepare 8. The product 9 was obtained as a white solid
(169 mg, 92%). FTIR (ATR): n˜ =3428, 2967, 2931, 1693, 1575, 1506,
meso-4’-(Ethynyloxy)phenylcalix[4]pyrrole (5): A mixture of compound
4 (0.669 g, 1.32 mmol), propargyl bromide (0,294 g, 1,98 mmol), and po-
tassium carbonate (0,365 g, 2.64 mmol) in DMF (50 mL) was reacted at
508C for 24 h. After the reaction was complete, DMF was removed
under vacuum and the resulting crude solid was dissolved in CH2Cl2. The
solution in CH2Cl2 was washed with water and dried over Na2SO4. Chro-
matographic purification (silica gel, CH2Cl2) yielded the compound 5 as a
white solid (0,650 g, 90%). 1H NMR (250 MHz, CDCl3): d=1.50–1.54
(brm, 18H; meso-CH3), 1.84 (s, 3H; meso-CH3), 2.50 (t, J=2.5 Hz, 1H;
1460, 1416, 1223, 1038, 766 cmÀ1 1H NMR (250 MHz, CDCl3): d=7.64–
;
7.54 (brm, 4H; CH), 7.24 (brs, 12H; NH), 7.11 (brs, 8H; NH), 6.89
(brd, J=6.9 Hz, 8H; ArH), 6.83 (brt, J=6.9 Hz, 8H; ArH), 5.88 (brs,
32H; pyrrole CH), 5.63 (brs, 8H; pyrrole CH), 5.13 (brs, 8H; CH2), 4.26
(brt, J=7.8 Hz, 8H; CH2), 1.83–1.23 ppm (brm, 128H; CH3, CH2);
13C NMR (126 MHz, CDCl3): d=138.9, 138.7, 138.5, 137.5, 137.0, 128.7,
114.0, 106.0, 103.3, 103.0, 62.3, 50.5, 44.2, 35.5, 35.4, 30.2, 29.9, 28.7 ppm;
LRMS (ESI): m/z (%): 3026 (100) [M+H+MeOH]+; HRMS (ESI): m/z
calcd for C189H229N32O5 [M+H+MeOH]+: 3029.8643; found: 3029.9435;
elemental analysis calcd (%) for C189H229N32O5: C 75.37, H 7.54, N 14.96,
O 2.14; found: C 74.56, H 8.72, N 14.02, O 1.86.
ꢀ
C CH), 4.65 (d, J=4.6 Hz, 2H; CH2), 5.65 (s, 2H; pyrrole CH), 5.89 (s,
6H; pyrrole CH), 6.81 (d, J=8.5 Hz, 2H; ArH), 6.91 (d, J=8.5 Hz, 2H;
ArH), 7.07 (brs, 2H; NH), 7.19 ppm (brs, 2H; NH); 13C NMR
(126 MHz, CDCl3): d=155.0, 139.8, 137.6, 137.4, 137.3, 135.7, 112.9,
104.8, 101.8, 101.8, 77.7, 74.4, 74.3, 54.8, 43.0, 34.2, 28.7, 27.5 ppm; LRMS
(ESI): m/z (%): 543.58 (100) [M]À; HRMS (ESI): m/z calcd for
C36H39N4O [M]À: 543.3129; found: 543.5832.
Tricalix[4]pyrrole (10): This compound was prepared by click reaction of
3
(219.27 mg, 407 mmol) and 1,3,5-tris(azidomethyl)benzene (30 mg,
Tetra-1-bromopentyltetramethylcalix[4]pyrrole (6): Pyrrole (1.74 g,
25.9 mmol) and 7-bromoheptane-2-one (5 g, 25.9 mmol) were dissolved
in dry MeOH (100 mL) at 08C and bubbled with argon for 10 min. Fol-
123.34 mmol), using the same procedure used to prepare 7. The product
10 was obtained as a white solid (215 mg, 94%). FTIR (ATR): n˜ =3424,
2967, 1729, 1577, 1419, 1226, 1166, 1040, 767 cmÀ1 1H NMR (250 MHz,
;
2004
www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2012, 18, 1999 – 2005

Tri- and Pentacalix[4]pyrroles
FULL PAPER
CDCl3): d=7.25 (brs, 6H; CH, ArH), 7.15 (brs, 12H; NH), 5.87 (brs,
24H; pyrrole CH), 5.41 (brs, 6H; CH2), 4.20–4.29 (brm, 6H; CH2), 2.91–
3.06 (brm, 6H; CH2), 2.13–1.73 (brm, 12H; CH2), 1.48–1.39 ppm (brm,
63H; CH3); 13C NMR (126 MHz, CDCl3): d=181.5, 172.5, 138.0, 137.6,
137.4, 135.2, 103.1, 101.8, 101.7, 61.9, 52.1, 37.4, 34.2, 28.2, 28.0, 24.5 ppm;
LRMS (ESI): m/z (%): 1857 (100) [M]À; HRMS (ESI): m/z calcd for
C111H135N21O6 [M]À: 1857.0904; found: 1857.8914; elemental analysis
calcd (%) for C111H135N21O6: C 71.70, H 7.32, N 15.82, O 5.16; found: C
71.98, H 7.04, N 16.12, O 5.48.
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5
(221.72 mg, 407 mmol) and 1,3,5-tris(azidomethyl)benzene (30 mg,
123.34 mmol), which was prepared from 1,3,5-tris(bromomethyl)benzene,
using the same procedure used to prepare 7. The dendrimer 11 was ob-
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1605, 1578, 1416, 1223, 1039, 768 cmÀ1 1H NMR (250 MHz, CDCl3): d=
;
7.56 (brs, 3H; CH), 7.25 (brs, 9H; NH, ArH), 7.13 (brs, 6H; NH), 6.92
(d, J=6.8 Hz, 6H; ArH), 6.83 (d, J=6.8 Hz, 6H; ArH), 5.88 (d, J=
À
5.8 Hz, 18H; pyrrole CH), 5.62 (s, 6H; pyrrole CH), 5.46 (s, 6H; N
À
CH2), 5.15 (s, 6H; O CH2), 1.83 (s, 9H; CH3), 1.54–1.49 (brm, 54H;
CH3); 13C NMR (126 MHz, CDCl3): d=137.6, 137.5, 137.3, 135.9, 135.7,
127.5, 112.8, 104.8, 101.8, 61.1, 52.3, 43.0, 34.2, 28.7, 27.5 ppm; LRMS
(ESI): m/z (%): 1906.95 (100) [M+MeOH]À; HRMS (ESI): m/z calcd
for C118H133N21O4 [M+MeOH]À: 1907.0849; found: 1906.9502; elemental
analysis calcd (%) for C118H133N21O4: C 74.85, H 6.93, N 15.67, O 2.56;
found: C 74.11, H 7.28, N 15.21, O 2.98.
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Acknowledgements
This work was supported by Scientific Research Projects Unit of Istanbul
Technical University (No. 34171).
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Received: May 25, 2011
Revised: September 21, 2011
Published online: January 11, 2012
Chem. Eur. J. 2012, 18, 1999 – 2005
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
2005