Calix[4]bis(spirodienone) as a versatile synthon for upper rim alkoxylation of calixarenes and synthesis of novel triazole-based biscalixarene by 'CuAAC' chemistry

Article abstract of DOI:10.1080/10610278.2011.556252

The spiro rings of calix[4]bis(spirodienone) have been opened up using various bromofunctionalised alcohols employing a novel ipso nucleophilic substitution of tert-butyl groups by alkoxy groups. Additionally, a route has been paved towards the preparation of triazole-linked biscalixarene via the copper(I)-catalysed modern version of classical Huisgen 1,3-dipolar cycloaddition of alkynyl calixarene and azidocalixarene, derived from the above-mentioned bromo-substituted calixarene.

Full text of DOI:10.1080/10610278.2011.556252

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Calix[4]bis(spirodienone) as a versatile synthon for
upper rim alkoxylation of calixarenes and synthesis
of novel triazole-based biscalixarene by ‘CuAAC’
chemistry
Sreeja Thulasi a , Anupriya Savithri a & Ramavarma Luxmi Varma a
a Organic Chemistry Section, Chemical Sciences and Technology Division, National Institute
for Interdisciplinary Science and Technology (CSIR), Trivandrum, 695 019, Kerala, India
Version of record first published: 09 May 2011.
To cite this article: Sreeja Thulasi , Anupriya Savithri & Ramavarma Luxmi Varma (2011): Calix[4]bis(spirodienone) as a
versatile synthon for upper rim alkoxylation of calixarenes and synthesis of novel triazole-based biscalixarene by ‘CuAAC’
chemistry, Supramolecular Chemistry, 23:7, 501-508
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Supramolecular Chemistry
Vol. 23, No. 7, July 2011, 501–508
Calix[4]bis(spirodienone) as a versatile synthon for upper rim alkoxylation of calixarenes and
synthesis of novel triazole-based biscalixarene by ‘CuAAC’ chemistry
Sreeja Thulasi, Anupriya Savithri and Ramavarma Luxmi Varma*
Organic Chemistry Section, Chemical Sciences and Technology Division, National Institute for Interdisciplinary Science and Technology
(CSIR), Trivandrum 695 019, Kerala, India
(Received 3 December 2010; final version received 5 January 2011)
The spiro rings of calix[4]bis(spirodienone) have been opened up using various bromofunctionalised alcohols employing a
novel ipso nucleophilic substitution of tert-butyl groups by alkoxy groups. Additionally, a route has been paved towards the
preparation of triazole-linked biscalixarene via the copper(I)-catalysed modern version of classical Huisgen 1,3-dipolar
cycloaddition of alkynyl calixarene and azidocalixarene, derived from the above-mentioned bromo-substituted calixarene.
Keywords: calixarene; calix[4]bis(spirodienone); p-TSA; biscalixarenes; CuAAC
Introduction
rim triazole-appended calixarenes bearing a-amino acids
and carbohydrates for performing chemo-enzymatic
procedures. Zhao and Chung et al. (14c,d) have validated
the use of this synthetic strategy for preparing triazole-
coupled calixarenes for binding of metal ions. Recently,
Gonzalez et al. (14f) have reported the synthesis of
calixarene-based cavitands and nanotubes by click
chemistry. In this context, we would like to report in this
article the systematic study on the selective monoalkox-
ylation of the upper rim of p-tert-butylcalix[4]arene using
bifunctional alcohols and a further demonstration of the
viability of CuAAC in the synthesis of a new head-to-head-
linked biscalixarene.
Biscalixarenes have garnered considerable interest as
fascinating calixarene derivatives for the study of various
aspects of their supramolecular chemistry from simple
host–guest interactions (1) to application as artificial
sensors (2), synthetic receptors for biological agents (3),
antibody mimetics (4) or building blocks for molecular
boxes (5). Biscalixarenes may be constructed through upper
rim–upper rim (6), lower rim–lower rim (7) and upper
rim–lower rim linkage or non-covalently generated through
hydrogen bonding (8). Rebek et al. (9) reported the synthesis
and encapsulation behaviour of biscalixarenes linked by one
bridge at the upper rim and bearing urea groups in the same
rims. A series of biscalixarene derivatives linked through
their upper rim with different aromatic and heteroaromatic
units as spacers between them has also been reported (10).
However, in most of the above-mentioned reports, there is
one limitation or another such as the poor availability of
starting materials, drastic reaction conditions, longer
reaction times and poor yield of the products.
As part of our ongoing research on the chemistry of
bis(spirodienones) (16) 1a, 1b and 1c (Figure 1) – the
highly versatile molecules obtained by the oxidative
cyclisation of p-tert-butylcalix[4]arene – we have recently
come across an interesting reaction in which the
bis(spirodienone) can be transformed into calix[4]arenes,
locked in the cone conformation, that are selectively
substituted with alkoxy/aryloxy groups at the upper rim
(17). The synthetic methodology adapted involved an acid-
mediated reaction of bis(spirodienone) with primary
alcohols to afford upper rim-substituted mono- and 1,3-
dialkoxy calix[4]arenes in a single step.
Our work in this direction was stimulated by the
tremendous impact exerted by copper-assisted azide–
alkyne cycloaddition (CuAAC) (11) (click reaction) (12) in
numerous areas of the material and life sciences (13) and
the belief that the use of this formidable reaction with
calixarenes will furnish the opportunity for new appli-
cations. Besides the advantage of efficiency, regioselec-
tivity and compatibility with reaction conditions, the
unique properties of the 1,4-disubstituted 1,2,3-triazole
ring, in terms of participation in hydrogen bonding and
dipole–dipole interactions, have made click chemistry
even more attractive (14). Click concept has been
ingeniously utilised by Bew et al. (15) for making upper
Results and discussion
With the aim of introducing additional functional groups at
the upper rim of calixarenes, we extended this newly
developed strategy using bifunctional alcohols. Initially,
we reacted bis(spirodienone) 1a with 3-bromopropan-1-ol
2a under conditions that have been optimised for alcohols
*Corresponding author. Email: lux_varma@rediffmail.com
ISSN 1061-0278 print/ISSN 1029-0478 online
q 2011 Taylor & Francis
DOI: 10.1080/10610278.2011.556252
http://www.informaworld.com

502
S. Thulasi et al.
But
But
tBu
But
But
But
S
S
R
O
O
O
O
O
O
O
O
O
O
S
O
O
R
S
tBu
But
But
But
But
tBu
1a (27%)
1b (9.1%)
1c (9.1%)
Figure 1. Oxidative cyclisation products of p-tert-butylcalix[4]arene.
Br
tBu
But
tBu
tBu
tBu
tBu
tBu
tBu
tBu
OTs
tBu
O
tBu
tBu
O
O
i
+
+
O
O
HO
OH OH
tBu
OH
HO
OH
OH OH OH HO
OH
OH
But
1a
3 (13%)
4a (39%)
5 (25%)
i = 3-bromopropan-1-ol (2a), 5.0 equiv. p-TSA, toluene, 110°C, 6 h.
Scheme 1. p-TSA-mediated reaction of calix[4]bis(spirodienone) 1a with bromopropanol.
(Scheme 1) (17). The optimised condition involved
in conducting the reaction in the presence of 5.0 equiv.
of p-TSA in toluene is 1108C for 6 h. The reaction afforded
a mixture of three products.
bromofunctionalised alcohols, the reaction proceeded
smoothly affording mono-substituted products in accep-
table yields.
When the reaction was carried out with 4-aminobutan-
1-ol 2d, to our disappointment no reaction took place and
the starting material was recovered as such. To understand
more about the non-reactivity of aminoalcohols, we
decided to investigate the reaction with highly nucleophilic
aliphatic amines. When substrate 1a was subjected to the
same reaction with diethylamine in the presence of p-TSA
(5.0 eqiuv.) in toluene at reflux temperature, reaction failed
to occur. The action of other Lewis acids such as AgOTf
and Sc(OTf)2 was also investigated but to no benefit. Thus,
the non-reactive nature of aminoalcohols was attributed to
the presence of amino group in the molecule. Under the
reaction conditions employed, the amino group gets
protonated owing to its high basicity.
Although products 3 and 5 were identified as p-tert-
butylcalix[4]arene and upper rim monotosylated calixarene
on comparison with literature data (17), the structure of 4a
was established by various spectroscopic techniques. In the
1H NMR spectrum, the hydroxyl proton was displayed as a
singlet at d 10.21 in units of parts per million (ppm). The
aromatic protons were discernible as a multiplet and a
singlet at d 7.03 and 6.55 ppm, respectively. The methylene
protons resonated as two broad doublets at d 4.23
(J ¼ 14.3 Hz) and 3.49 ppm. An uneven triplet at d
3.93 ppm was observed for the OCH2 protons. The tert-
butyl group appeared as two singlets at d 1.21 and 1.19 ppm
in a 2:1 ratio with one tert-butyl group missing. The
proposed structure was further supported by 13C NMR
spectrum showing an OCH2 peak at d 65.5 ppm. The
aromatic carbon to which OH was attached resonated at
d152.9 ppm. Thealiphaticsignals were observedin d34.1–
15.1 ppm region. The cone conformation was confirmed
from 13C values obtained for methylene bridges and by
comparison with literature precedents (18). The structure
was further confirmed by CHN analysis (anal. calcd for
C43H53BrO5: C, 70.77; H, 7.32. Found: C, 70.73; H, 7.35).
To establish the general nature of the reaction, we
further reacted substrate 1a with various bromoalcohols
and an aminoalcohol under the optimised conditions. The
results are summarised in Table 1. In the case of
The possibility of facile conversion of bromo
derivative to azide functionality prompted us to utilise
the phenomenon of click chemistry in the construction of
multivalent structures such as biscalixarenes. The alkyne
partner for the click reaction was also prepared by the
same synthetic methodology (17).
Preliminary endeavours towards click reaction focused
on utilising one-pot in situ azide synthesis/‘click’ protocol
reported by Van der Eycken et al. (19). Treating
bromofunctionalised calixarene 4a, sodium azide and
upper rim propargylated calixarene 4e in DMSO at 808C
for 12 h did not yield the desired click calixarene adducts.
All of the starting materials were recovered in good mass

Supramolecular Chemistry
503
presence of CuI and CuSO4/Na ascorbate combination but
without much success. Interestingly, employing CuSO4/Na
ascorbate in aqueous ethanol at 608C gave solely the 1,5-
disubstituted triazole-linked biscalixarene in 77% yield
(Scheme 3). The structure of compound 6 was
characterised by NMR analysis and MALDI-TOF spectral
data (Table 2).
Table 1. Generalisation of the reaction with various functio-
nalised alcohols.
tBu
But
tBu tBu
OR
tBu
3 +
O
O
O
+ 5
O
1
The H NMR of 6 exhibited the triazole proton at d
tBu
OH OH OH HO
But
7.51 ppm as a singlet. Moreover, the fixed cone
conformation of the calix[4]arene scaffolds was substan-
tiated by the presence of signals for the equatorial and
axial protons of the methylene bridges as doublets at ca 4
and 3 ppm, respectively. The OH protons of the two
calixarene units appeared as two singlets close to each
other at d 10. 23 and 10.21 ppm. The various CH2 protons
appeared as corresponding signals at d 5.03 (singlet), 4.45
(triplet), 3.81 (triplet), 2.29 (multiplet) ppm. The 13C NMR
of 6 exhibited a peak at d 153 ppm attributable to carbon to
which OH is attached. The aliphatic carbon cluster
representing t-Bu and bridging methylenes appeared
within 34–29 ppm range. An HMQC experiment was
run to assign carbons due to various CH2s and triazole CH,
which allowed the assignment of peaks at 64.3 and
62.1 ppm to ZNCH2 and ZOCH2 (near to triazole ring),
respectively. The ZOCH2 near the calixarene moiety was
seen at 49.9 ppm whereas the triazole CH appeared
immersed in a cluster of aromatic carbon around 127 ppm.
As a follow-up of the investigation described above, it
was of interest to study the [2 þ 3]-cycloaddition of
azidocalixarene with various phenylacetylenes, which
were prepared by the Sonogashira reaction of respective
bromobenzenes and TMS acetylene using literature
procedures (20). Interestingly, on reacting 4a0 with phenyl
acetylene 7 using CuSO4/sodium ascorbate in aqueous
ethanol at ambient temperature gave solely the triazole-
linked calixarene 8 in 85% yield (Scheme 4).
4a-c
1a
Yield (%)
Entry
ROH 2(a-d)
4
3
5
(2a)
1
4a/39
4b/35
4c/28
25
23
27
OH
13
20
20
Br
OH
(2b)
OH
(2d)
2
3
4
Br
Br
(2c)
No Reaction
OH
H2N
Reaction conditions: 2, 5.0 equiv. p-TSA, toluene, 110°C, 6h.
balances. Switching to a stepwise protocol, we readily
undertook the synthesis of the core starting material 4a0
via SN2 displacement on bromofunctionalised calixarene
(Scheme 2).
Having both the partners for the cycloaddition in hand,
we next turned our attention to clicking between the two.
Utilising a procedure reported by Sharpless et al. (11a), we
attempted a copper(I)-catalysed [3 þ 2]-dipolar cycload-
dition reaction between calix[4]arene derivatives. Accord-
ingly, an aqueous tert-butyl alcohol (1:1 v/v) solution of 4a0
and 4e was stirred (96 h) at ambient temperature
with copper(II) sulphate and sodium ascorbate. However,
the reaction failed to afford any product due to solubility
problems, and the starting materials were recovered
unchanged. Even though the solubility problem was
alleviated by changing the solvent to aqueous DMF, no
reaction ensued, both at ambient and reflux temperature.
Solvents such as THF and CH3CN were also used in the
This result obtained with phenylacetylene encouraged
us to extend the Cu(I)-catalysed cycloaddition reaction of
azidocalixarene 4a0 to diacetylene and triacetylene
benzenes. Accordingly, we attempted the reaction of
azidocalixarene with diacetylene benzene 9 and triacety-
lene benzene 11 under similar conditions. Results revealed
Br
N3
tBu
tBu
tBu tBu
tBu
O
tBu
O
NaN3
DMSO,rt, 24 h
HO
OH OH OH HO
OH
OH OH
4a
4a' (99%)
Scheme 2. Reaction of 4a with NaN3.

504
S. Thulasi et al.
OH
OH
OH
HO
HO
HO
HO
OH
tBu
tBu
tBu
O
tBu
N
O
tBu
tBu
N
4e
+
N
i
N3
tBu
tBu tBu
O
tBu
tBu
OH
tBu
O
HO
OH
OH
OH
HO
6
OH
4a'
OH
i = CuSO4/Na ascorbate, iPrEA, EtOH/H2O (2:1), 60˚C, 2h.
Scheme 3. [3 þ 2] Cycloaddition of alkynyl calixarene 4e with azidocalixarene 4a0.
that in the above cases the respective triazole-appended
calixarenes 10 and 12 were obtained as the sole products in
excellent yields. The gross structures of both the products
All the solvents were purified according to the standard
procedure; dry solvents were obtained according to the
literature methods and stored over molecular sieves.
Analytical thin layer chromatography was performed on
glass plates coated with silica gel containing calcium
sulphate binder. Gravity column chromatography was
performed using 100–200 mesh silica gel and mixtures of
hexane–ethyl acetate were used for elution.
1
were determined by IR, H, 13C NMR and MALDI-TOF
analyses.
The host–guest properties of biscalixarene 6 were
investigated in the presence of metal ions (Liþ, Naþ, Kþ,
Csþ, Mg2þ, Ca2þ, Sr2þ, Ba2þ, Agþ, Cu2þ, Zn2þ, Cd2þ
,
Hg2þ and Pb2þ), organic anions (tBuNCl, tBuNBr,
tBuNHSO4 and tBuNClO4) and small molecules
(CH3OH and CH3NH2). The compound was found to be
inactive in binding towards the various guests examined.
The studies of other multicalixarenes are going on and will
be duly reported.
NMR spectra were recorded at 300 MHz (1H) and
75 MHz (13C), respectively, on a Bruker Avance DPX-
300 MHz. Chemical shifts are reported in d (ppm) relative
to TMS (1H) or CDCl3 (13C) as internal standards. IR
spectra were recorded on Bomem MB series FT-IR
spectrometer; absorptions are reported in cm21. Mass
spectra were recorded under MALDI-TOF mechanism in
Axima-CFR Plus spectrometer. Elemental analysis was
done using Perkin-Elmer 2400 CHNS analyser. Chemical
shifts for 1H NMR spectra are reported as d (ppm)
downfield from SiMe4 (d 0.0) and relative to the signal of
chloroform-d (d 7.25, singlet). Multiplicities were given as
s (singlet), br s (broad singlet), d (doublet), t (triplet) and
dd (doublets of doublet). Coupling constants are reported
as J value in Hz. Carbon nuclear magnetic resonance
spectra (13C NMR) are reported as d (ppm) downfield
from SiMe4 (d 0.0) and relative to the signal of
chloroform-d (d 77.03, triplet). Elemental analysis was
done using Perkin-Elmer 2400 CHN analyser.
Conclusion
In summary, we have employed bromoalcohols, in the
presence of p-TSA, to open up the spiro rings of
calix[4]bis(spirodienone) to furnish upper rim bro-
moalkyl-substituted calix[4]arenes. Furthermore, we
have utilised this new upper rim bromo-substituted
calixarene as a starting point in the synthesis of
biscalixarene linked in an upper rim–upper rim fashion
together with propargyl-substituted calixarene (obtained
using the same synthetic methodology) via CuAAC. The
high yield and exclusive formation of 1,4-disubstituted
triazole highlight the efficiency of the approach.
General procedure for the reaction of
calix[4]bis(spirodienone) with bromoalcohols
Experimental
General procedures and materials
A mixture of bis(spirodienone) 1a (50 mg, 0.08 mmol),
bromoalcohol (4.0 equiv.) and p-TSA (5.0 equiv.) in toluene
was taken in a 50 ml R.B. flask and was stirred at 1108C.
All the chemicals were of the best grade commercially
available and were used without further purification.

Supramolecular Chemistry
Table 2. Triazole-linked calix[4]arene frameworks from 4a0.
505
Entry
Acetylenes
Products (yield)
tBu
tBu
tBu
HO
HO
HO
O
1
N
N
HO
N
9
N
N
N
OH
10 (82%)
O
OH
OH
tBu
tBu
HO
OH
HO
HO
tBu
HO
tBu
2
tBu
tBu
O
11
tBu
N N
OH
N
tBu
tBu
OH
OH
tBu
HO
HO
HO
OH
O
tBu
N
N
N
N
O
N
N
tBu
HO
12 (76%)
Reaction conditions: 4a′, CuSO4/Na ascorbate, DIPEA, EtOH/H2O (2:1), rt, 2h
N
N
N
N3
tBu
tBu
tBu
tBu
O
tBu
tBu
O
i
+
HO
HO
OH
OH
OH
7
OH OH OH
8 (85%)
4a'
i = CuSO4/Na ascorbate, DIPEA, EtOH/H2O (2:1), rt, 2h.
Scheme 4. Reaction of azidocalixarene with phenylacetylene under ‘click’ protocol.

506
S. Thulasi et al.
The reaction was continued till the reaction was complete as
shown by TLC (,6 h). The solvent was removed under
reduced pressure. The reaction mixture was worked up
using dichloromethane–water mixture and the solid mass
obtained was purified by column chromatography.
(MALDI-TOF): calcd for C47H61BrO5, [M þ Na]þ:
807.37; found: 807.45.
General procedure for the reaction of
calix[4]bis(spirodienone) with propargyl alcohol
A mixture of bis(spirodienone) 1a (50 mg, 0.08 mmol),
alcohol (4.0 equiv.) and p-TSA (5.0 equiv.) in toluene was
taken in a 50 ml R.B flask and was stirred under reflux
temperature (1108C). The refluxing was continued till
the reaction was complete as shown by TLC (,10 min).
The solvent was removed under reduced pressure.
The reaction mixture was worked up using dichlor-
omethane–water mixture and the solid mass obtained was
purified by column chromatography.
5-(3-Bromoprop-1-oxy)-11,17,23-tris(1,1-dimethylethyl)-
25,26,27,28-tetrahydroxycalix[4]arene (4a)
Yield: 39% as a white solid. Rf: 0.86 (90:10 hexane–ethyl
acetate). Mp: Decomposed .2308C. IR (KBr) nmax: 3172,
2960, 2862, 1814, 1258, 1050 cm21. 1H NMR: d 10.21 (s,
OH, 4H), 7.03 (m, ArH, 6H), 6.55 (s, ArH, 2H), 4.23
(broad s, ArCH2Ar, 4H), 3.93 (uneven t, ZOCH2, 2H),
3.49 (m, ArCH2Ar, ZCH2, 6H), 2.16 (m, ZCH2, 2H), 1.21
(s, t-Bu, 18 H), 1.19 (s, t-Bu, 9H). 13C NMR: d 152.9 (C–
OH), 146.8, 146.7, 146.3, 144.4, 144.2, 142.8, 129.4,
127.9, 127.7, 127.2, 126.0, 125.9, 125.6, 114.6 (Ar-C),
65.5 (ZOCH2), 56.9 (ZCH2Br), 34.1, 31.5, 30.8, 29.9,
29.4, 22.7, 14.1 (ArCH2Ar, ZCH2, t-Bu). MS (FAB): calcd
for C43H53BrO5, [M þ 1]þ: 729.31; found: 729.64,
730.58. Elemental analysis calculated for C43H53BrO5:
C, 70.77; H, 7.32. Found: C, 70.73; H, 7.35.
5-(Prop-3-yn-1-oxy)-11,17,23-tris(1,1-dimethylethyl)-25,
26,27,28-tetrahydroxycalix[4]arene (4e)
Yield: 33% as a white powder. Rf: 0.88 (90:10 hexane–
ethyl acetate). Mp: Decomposed .2408C. IR (KBr) nmax
:
1
3175, 2960, 2858, 2135, 1259, 1053 cm21. H NMR: d
10.23 (s, OH, 4H), 7.03 (m, ArH, 6H), 6.65 (s, ArH, 2H),
4.51 (s, ZOCH2, 2H), 4.23 (d, J ¼ 14.3 Hz, ArCH2Ar,
4H), 3.46 (broad s, ArCH2Ar, 4H), 2.42 (s, acetylenic H,
1H), 1.22 (s, t-Bu, 18 H), 1.19 (s, t-Bu, 9H). 13C NMR: d
152.0 (C–OH), 146.9, 146.3, 144.5, 144.4, 143.4, 130.9,
129.4, 128.9, 128.4, 127.9, 127.6, 127.1, 125.9, 125.7,
115.1 (Ar-C), 78.9, 75.4 (acetylenic carbons), 56.1
(ZOCH2), 34.1, 34.0, 32.6, 31.6, 29.8, 14.2 (ArCH2Ar,
t-Bu). MS (FAB): calcd for C43H50O5, [M þ 1]þ: 647.36;
found: 647.37. Elemental analysis calculated for
C43H50O5: C, 79.84; H, 7.79. Found: C, 79.80; H, 7.76.
5-(4-Bromobut-1-oxy)-11,17,23-tris(1,1-dimethylethyl)-
25,26,27,28-tetrahydroxycalix[4]arene (4b)
Yield: 35% as a white solid. Rf: 0.83 (90:10 hexane–ethyl
acetate). Mp: Decomposed .2308C. IR (KBr) nmax: 3171,
2957, 2860, 1810, 1258, 1050 cm21. 1H NMR: d 10.21 (s,
OH, 4H), 7.02 (m, ArH, 6H), 6.54 (s, ArH, 2H), 4.24 (d,
J ¼ 13.5 Hz, ArCH2Ar, 4H), 3.81 (t, J ¼ 6.0 Hz, ZOCH2,
2H), 3.44 (m, ArCH2Ar, ZCH2, 6H), 1.98 (m, ZCH2, 2H),
1.84 (s, ZCH2, 2H), 1.22 (s, t-Bu, 18H), 1.19 (s, t-Bu, 9H).
13C NMR: d 157.6 (C–OH), 146.8, 144.3, 129.3, 127.9,
127.7, 127.2, 126.0, 125.8, 125.6, 114.5 (Ar-C), 66.8
(ZOCH2), 52.4 (ZCH2Br), 34.0, 33.2, 32.5, 31.5, 31.4,
29.4, 27.9 (ArCH2Ar, ZCH2, t-Bu). MS (FAB): calcd for
C44H55BrO5, [M þ 1]þ: 743.81; found: 743.95, 744.84.
Elemental analysis calculated for C44H55BrO5: C, 71.05;
H, 7.45. Found: C, 71.08; H, 7.48.
Procedure for the synthesis of azidocalixarene (4a0)
To a solution of 4a (50 mg, 0.07 mmol) in 2 ml
dichloromethane, a 0.5 M solution of NaN3 in DMSO
(20 ml) was added and stirred at 258C for 2 days. The
reaction was quenched with water (10 ml) and stirred until
it cooled to room temperature. The reaction mixture was
washed with water (2 £ 20 ml) and once with brine
(10 ml). The organic layer was dried (anhydrous Na2SO4),
filtered and the solvent removed under vacuum to alkyl
azide 4a0 in almost quantitative yield (93 mg, 99%). Rf:
0.86 (80:20 hexane–ethyl acetate). Mp: Decomposed
.2308C. IR (KBr) nmax: 2960, 2102, 1814, 1358,
5-(7-Bromohept-1-oxy)-11,17,23-tris(1,1-dimethylethyl)-
25,26,27,28-tetrahydroxycalix[4]arene (4c)
Yield: 28% as a white pasty mass. Rf: 0.82 (90:10 hexane–
ethyl acetate). IR (KBr) nmax: 3171, 2957, 2860, 1810,
1258, 1050 cm21. 1H NMR: d 10.20 (s, OH, 4H), 7.03 (m,
ArH, 6H), 6.54 (s, ArH, 2H), 4.22 (broad s, ArCH2Ar, 4H),
3.77 (t, J ¼ 6.5 Hz, ZOCH2, 2H), 3.38 (m, ArCH2Ar,
ZCH2, 6H), 1.85 (m, ZCH2, 2H), 1.22 (m, t-Bu, ZCH2,
33H), 0.88 (m, ZCH2, 2H). 13C NMR: d 157.9 (C–OH),
146.2, 144.2, 129.2, 125.9, 125.8, 125.6, 114.4 (Ar-C),
60.8 (ZOCH2), 44.3 (ZCH2Br), 34.0, 33.6, 32.7, 31.5,
29.7, 29.2, 28.6, 28.1 (ArCH2Ar, ZCH2, t-Bu). MS
1060 cm21 1H NMR: d 10.22 (s, OH, 4H), 7.06 (m,
.
ArH, 6H), 6.43 (s, ArH, 2H), 4.23 (broad s, ArCH2Ar, 4H),
3.86 (uneven t, ZOCH2, 2H), 3.50 (m, ArCH2Ar, CH2,
6H), 2.13 (m, ZCH2, 2H), 1.22 (s, t-Bu, 18 H), 1.19 (s, t-
Bu, 9H). 13C NMR: d 156.2 (C–OH), 149.8, 149.1, 146.2,
144.3, 131.1, 129.7, 129.5, 129.1, 128.8, 127.7, 127.4,
116.3 (Ar-C), 63.4, 56.9, 34.1, 32.6, 31.6, 31.5, 15.1
(ArCH2Ar, ZCH2s, t-Bu). MS (FAB): calcd for

Supramolecular Chemistry
507
C43H53N3O5, [M þ 1]þ: 692.89; found: 692.96. Elemental
General procedure for the click reaction between
azidocalixarene and phenylacetylenes
analysis calculated for C43H53N3O5: C, 74.64; H, 7.72; N,
6.07. Found: C, 74.83; H, 7.35; N, 5.98.
Phenylacetylene, CuSO4·5H2O, sodium ascorbate and
DIPEA were added to a solution of azidocalixarene 4a0 in
2:1 EtOH/H2O (20 ml) mixtures. The mixture was stirred
at ambient temperature for 2 h, when the TLC indicated
the absence of azidocalixarene. Evaporation of solvent
followed by work up using CHCl3/H2O yielded a crude
mixture. The solid mass obtained was purified by column
chromatography in hexane–ethyl acetate solvent system.
Typical procedure for the preparation
of phenylacetylenes
To a mixture of bromobenzene, PdCl2(PPh3)2 (10 mol %),
CuI (20 mol %) and PPh3 (20 mol %) under an argon
atmosphere were added Et3N (30 ml) and then a solution of
TMS acetylene in Et3N (10 ml). The resulting mixture was
stirred at refluxing temperature for 24 h. After evaporation
of Et3N, the residue was triturated with CHCl3 and filtered.
The filtrate was partitioned between CHCl3 and H2O,
where the aqueous layer was neutralised with diluted HCl.
The organic layer was washed with H2O and brine and
dried over anhydrous Na2SO4. After evaporation of
solvent, the residue was subjected to column chromatog-
raphy on silica gel eluted with hexane–CHCl3 (1.7:1) to
give slightly crude phenylacetylenes substituted by TMS.
The TMS group was deprotected using tetrabutylammo-
nium fluoride to afford phenylacetylenes in excellent
yield.
Compound 8
Rf: 0.64 (70:30 hexane–ethyl acetate). Mp: .2508C. IR
(KBr) nmax: 3428, 3255, 1635, 1392, 1284, 1144,
984 cm21. 1H NMR: d 10.21 (s, OH, 4H), 7.41 (s, triazole
CH, 1H), 7.04 (m, ArH, 11H), 6.54 (s, ArH, 2H), 4.25 (d,
J ¼ 13.5 Hz, ArCH2Ar, 4H), 3.90 (t, J ¼ 6.0 Hz, ZOCH2,
2H), 3.49 (m, ArCH2Ar, ZCH2, 6H), 2.39 (m, ZCH2, 2H),
1.22 (s, t-Bu, 18 H), 1.19 (s, t-Bu, 9H). 13C NMR: d 152.9
(C–OH), 146.8, 146.7, 146.3, 144.4, 144.2, 129.4, 127.9,
127.7, 126.0, 125.8, 125.6, 114.6 (Ar-C), 65.5, 46.7, 34.1,
34.0, 32.8, 32.7, 32.5, 31.9, 31.5, 30.8, 29.8, 29.7, 29.4,
22.7, 14.2 (ArCH2Ar, ZCH2s, t-Bu). MS (MALDI-TOF):
calcd for C51H59N3O5, [M þ 23]þ: 817.03; found: 817.27.
Procedure for the synthesis of triazole-functionalised
biscalixarene 6
Compound 10
A mixture of calix[4]arene azide 4a0 (76 mg, 0.10 mmol),
alkynyl calixarene 4e (110 mg, 0.20 mmol), freshly
distilled N,N-diisopropylethylamine (175 ml, 1.00 mmol),
CuSO4 (8.0 mg, 0.05 mmol), sodium ascorbate (99 mg,
0.5 mmol) and EtOH/H2O (20 ml, 1:2) was magnetically
stirred at 608C for 2 h, diluted with AcOEt, washed with
water, dried (Na2SO4) and concentrated. The solid mass
obtained was purified by column chromatography.
Rf: 0.57 (70:30 hexane–ethyl acetate). Mp: Decomposed
.2308C. IR (KBr) nmax: 3456, 2954, 1640, 1484, 1210,
1
1123, 909 cm21. H NMR: d 10.21 (s, OH, 8H), 7.85 (s,
ArH, 4H), 7.76 (s, triazole CH, 2H), 7.03 (m, ArH, 12H),
6.58 (s, ArH, 4H), 4.56 (t, J ¼ 7.0 Hz, ZOCH2, 4H), 4.25
(broad s, ArCH2Ar, 8H), 3.86 (t, J ¼ 6.0 Hz, ZNCH2, 4H),
3.46 (m, ArCH2Ar, 8H), 2.29 (m, ZCH2, 4H), 1.23 (s, t-
Bu, 36H), 1.19 (s, t-Bu, 18H). 13C NMR: d 152.8 (C–OH),
146.8, 146.2, 144.5, 129.5, 127.9, 127.7, 126.1, 125.9,
125.6, 120.2, 114.6 (Ar-C), 64.5, 62.1, 34.1, 32.5, 31.5,
31.4, 29.7, 23.7, 15.1 (ArCH2Ar, ZCH2s, t-Bu). MS
(MALDI-TOF): calcd for C96H112N6O10, [M]þ: 1531.84;
found: 1532.29.
Compound 6
Rf: 0.54 (70:30 hexane–ethyl acetate). Mp: Decomposed
.2308C. IR (KBr) nmax: 3467, 1640, 1484, 1296, 1203,
1
1123, 1064 cm21. H NMR: d 10.23 (s, OH, 4H), 10.21
Compound 12
(s, OH, 4H), 7.51 (s, triazole CH, 1H), 7.03 (m, ArH,
12H), 6.68 (s, ArH, 2H), 6.55 (s, ArH, 2H), 5.03 (s,
ZOCH2, 2H), 4.45 (t, J ¼ 7.5 Hz, ZOCH2, 2H), 4.24 (d,
J ¼ 13.5 Hz, ArCH2Ar, 8H), 3.81 (t, J ¼ 5.0 Hz,
ZNCH2, 2H), 3.47 (m, ArCH2Ar, 8H), 2.29 (m,
ZCH2, 2H), 1.22 and 1.19 (s, t-Bu, 54 H). 13C NMR:
d 152.7 (C–OH), 146.8, 146.3, 144.5, 143.2, 143.0,
129.4, 127.9, 127.7, 127.1, 126.1, 125.9, 125.8, 114.9,
114.6 (Ar-C), 64.3, 62.1, 49.9 (ZCH2), 34.1, 34.0, 32.5,
31.5, 31.4, 29.7, 22.7 (ArCH2Ar, ZCH2, t-Bu). MS
(MALDI-TOF): calcd for C86H103N3O10, [M]þ: 1337.76;
found: 1337.26.
Rf: 0.48 (70:30 hexane–ethyl acetate). Mp: Decomposed
.2308C. IR (KBr) nmax: 3354, 1667, 1440, 1225, 1113,
1038, 788 cm21. 1H NMR: d 10.22 (s, OH, 12H), 7.91 (s,
ArH, 3H), 7.79 (s, triazole CH, 3H), 7.14 (m, ArH, 18H),
6.62 (s, ArH, 6H), 4.58 (t, J ¼ 7.2 Hz, ZOCH2, 6H), 4.26
(broad s, ArCH2Ar, 12H), 3.92 (t, J ¼ 6.1 Hz, ZNCH2,
2H), 3.50 (m, ArCH2Ar, 12H), 2.35 (m, ZCH2, 6H), 1.25
(s, t-Bu, 54 H), 1.19 (s, t-Bu, 27H). 13C NMR: d 153.2 (C–
OH), 147.3, 146.8, 145.3, 129.6, 128.1, 127.5, 126.5,
126.1, 125.1, 122.4, 116.3 (Ar-C), 65.3, 62.4, 34.0, 32.1,
31.2, 29.5, 22.1, 15.3 (ArCH2Ar, ZCH2s, t-Bu). MS

508
S. Thulasi et al.
(MALDI-TOF): calcd for C141H165N9O15, [M þ 1]þ:
(f) Kumar, M.; Bhalla, V.; Babu, J.N. Tetrahedron 2003, 59,
3267–3273.
2225.26; found: 2225.54.
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Acknowledgements
This work was supported by Council of Scientific and Industrial
Research (CSIR) (NWP 0023) and the Department of Science
and Technology (DST), New Delhi. S.T. and A.S. acknowledge
the UGC and CSIR for research fellowships. The authors also
thank Mr B. Adarsh and Ms S. Viji for recording NMR and Mass
spectra, respectively.
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