Shaping the cavity of calixarene architecture for molecular recognition: synthesis and conformational properties of new azocalix[4]arenes

Article abstract of DOI:10.1016/j.tet.2006.05.040

A series of new azocalix[4]arenes containing one, two, three, and four free phenolic groups have been synthesized through the reaction of 4-nitro- and 2,4-dinitrophenylhydrazines with flexible calix[4]arene diquinones as well as through diazocoupling reac

Full text of DOI:10.1016/j.tet.2006.05.040

Tetrahedron 62 (2006) 7854–7865
Shaping the cavity of calixarene architecture for molecular
recognition: synthesis and conformational properties
of new azocalix[4]arenes
*
Har Mohindra Chawla, Suneel Pratap Singh, Satya Narayan Sahu and Shailesh Upreti
Department of Chemistry, Indian Institute of Technology, Hauz khas, New Delhi 110 016, India
Received 28 January 2006; revised 27 April 2006; accepted 18 May 2006
Available online 21 June 2006
Abstract—A series of new azocalix[4]arenes containing one, two, three, and four free phenolic groups have been synthesized through the
reaction of 4-nitro- and 2,4-dinitrophenylhydrazines with flexible calix[4]arene diquinones as well as through diazocoupling reactions of
calix[4]arenes. Characterization of synthesized compounds by spectroscopic methods and X-ray diffraction revealed that azocalix[4]arenes
adopt a cone conformation if they contain at least one free phenolic group. Partial cone or 1,3-alternate conformers of azocalix[4]arenes result
only when they are devoid of free phenolic groups. The results can be utilized to shape calix[4]arene architecture for ionic and molecular
recognition.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
which can be utilized for development of specific molecular
diagnostics and sensor materials.
Calix[n]arenes (n¼4–20) are phenolic [1]n-metacyclo-
phanes,1 which can be synthesized through acid or base
catalyzed condensation of p-substituted phenols and formal-
dehyde. They possess easily functionalizable hydrophobic
upper rim and hydrophilic lower rim to encompass a hollow
cavity, the dimensions of which depend upon their con-
formation and appended functional groups.2 The observed
diversity of calix[n]arenes essentially lies in their conforma-
tional isomerism due to rotation of Ar–CH2–Ar bonds or
molecular rotation through the annulus.3 Different stable
conformers of calix[4]arenes have different capabilities for
ionic and molecular recognition.4
A number of azocalix[n]arenes have recently been examined
for metal ion recognition.6 Apparently, azocalix[4]arenes de-
void of the possibility of intramolecular hydrogen bonding
have not been examined to a great extent, as deprotonation
of phenolic hydroxyls to elicit shift in the UV–vis spectra
as an analytical signal (Fig. 1)7 is not possible in such cases.
Mere involvement of intramolecular hydrogen bonding to
explain the observed role of hydrophobic cavity and its size
and shape in molecular and ionic recognition needs to be
explored further.8 In order to understand the recognition
characteristics of azocalix[n]arenes better, one is required
to develop rational methods for obtaining cone, partial
cone or alternate conformations of chromogenic calixarenes
to examine their differential host–guest interaction to arrive
at conclusions, which may define the role of weak interaction
in the ionic recognition by azocalix[4]arenes. In this paper,
we report our exploration in the role of hydrogen bonding
in shaping the cavity of azocalixarenes and methods to
achieve their different conformers. The choice of pyridylazo-
and nitrophenylazo- groups as chromogens was motivated by
the assumption that these functions when present in cone,
partial cone, and 1,3-alternate conformations would allow
better sensing capability for cations and neutral organic
guests even in the absence of free phenolic hydroxyls.
Assignment of the conformational structure of synthesized
azocalix[4]arenes has been inferred from examination of
their NMR splitting patterns and structure determination
through single crystal X-ray diffraction.
Though X-ray structure analysis is the final diagnosis for the
determination of conformation of calix[n]arenes, it has now
been established that 1H NMR and 13C NMR spectral analy-
sis can be effectively employed for conformational analysis.
For instance, when the phenolic units around each methylene
unit are in a syn orientation, the methylene carbon appears
around d 31 when phenolic units are in an anti orientation
with respect to each other, the methylene carbon appears
around d 375 in the 13C NMR spectrum of calix[4]arenes.
Introduction of azo groups into the calix[n]arene frame-
work confers chromogenicity to their molecular architecture,
Keywords: Calix[n]arenes; Diazotization; Conformation; Hydrogen bond.
* Corresponding author. Tel.: +91 11 26591517; fax: +91 11 26591502;
e-mail: hmchawla@chemistry.iitd.ernet.in
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.05.040

H. M. Chawla et al. / Tetrahedron 62 (2006) 7854–7865
7855
(a)
O
O
O
O
O
O
H
N
N
H
N
N
N
N
N
O
N
O
N
O
H
2+
OCH3
(b)
H3CO
Hg
H3CO
OCH3
2+
Hg
N
H N
H
N
N
N
N
N
N
O
O
O
O
O
O
O
O
H
H
H
H
H
H
Figure 1. (a) Suggested mechanism of conversion of azo phenol moiety to quinoidal form; (b) an example of ionic recognition through azo quinoidal form.
R
2R4
2. Results and discussion
R1
R3
2.1. Results and characterization of the products
i
O
O
Calix[n]arenes bearing p-nitrophenylazo- and pyridylazo-
chromogens containing one, two, three or four free phenolic
groups in calix[4]arenes were synthesized either through the
diazocoupling reaction of corresponding diazotized amines
with calix[4]arene derivatives or through the reaction of
nitrosubstituted phenyl hydrazines with calix[4]arene di-
quinones. Some of the derivatives were afforded through
acylation or benzoylation of calix[4]arene derivatives. The
choice of calix[4]arene diquinones as the starting materials
for affording some of the derivatives was based upon their
conformational flexibility and possible availability of partial
cone conformation. Reaction conditions described in the
Section 4 allowed the isolation of compounds, which were
O
O
O
O
O
O
H
H
H
H
H
H
H
H
No.
R1
R2
R3
R4
1
1a
1b
1c
1d
1e
3-AP
3-AP 3-AP
3-AP
3-AP 3-AP
3-AP 3-AP
N
3-AP =
3-AP
3-AP
3-AP
N
N
3-Azo pyridyl
3-AP
Scheme 1. Synthesis of azocalix[4]arenes with four free phenolic groups.
Reagents and conditions (i) diazonium salt obtained from 3-aminopyridine,
DMF/MeOH, CH3COONa, 0–5 ꢀC, 3 h.
R
R
R
1
identified by examination of their H and 13C NMR and
(i)
FAB mass spectra, NOESY experiments and X-ray diffrac-
tion analysis (for 3b and 12a).
O
O
O
O
O
O
O
O
H3C
H
H
2
H
H3C
H
H
H
Azocalix[4]arenecontaining fourfreephenolicgroups (1a–e)
were synthesized by the diazonium coupling reaction of
diazotized aromatic amines and calix[4]arene (1) by employ-
ing the method reported earlier9 (Scheme 1). The identity of
purified products was confirmed by comparison with authen-
tic samples and analysis of their spectral data (IR, NMR).
2aR= 3-AP (3-azo pyridyl)
2b R= 4-NP (4-nitro phenyl azo)
Scheme 2. Synthesis of azocalix[4]arenes with three free phenolic groups.
Reagents and conditions (i) diazonium salt obtained from respective amine,
DMF/MeOH, CH3COONa, 0–5 ꢀC, 3 h.
yields (21–56%) by reacting dialkylated calix[4]arenes at
0–5 ꢀC with 3 equiv of diazonium salt obtained from the cor-
responding amine in DMF/methanol (8:5) in the presence of
sodium acetate as a base for adjustment of pH of the reaction
(pH 7–9).
Azocalix[4]arenes containing three free phenolic groups (2a,
2b) were obtained by the diazonium coupling reaction of
pyridyl or 4-nitrophenyl diazonium chloride and mono-
methoxy-calix[4]arene at 0–5 ꢀC in DMF/methanol (8:5) in
the presence of sodium acetate (pH 7–9) (Scheme 2). The
products were isolated as red powders, which were character-
ized as 2a and 2b by spectral measurements.
13C NMR spectra of the synthesized derivatives revealed that
their methylene carbon appears at d 31.0 indicating that the
synthesized compounds were in their cone conformation in
accordance with the earlier findings on conformational as-
signment in calix[4]arenes.5 It was interesting to note that
The synthesis of azocalix[4]arenes containing two free phe-
nolic groups (3a–6a, Scheme 3) was achieved in moderate

7856
H. M. Chawla et al. / Tetrahedron 62 (2006) 7854–7865
R2
the diester derivative 3a and 3b displayed a quartet or a pair
R3
of doublet for the –OCH2CO– protons at d 4.71 and 4.75, re-
spectively, in their 1H NMR spectra as against the expected
singlet for these protons (Supplementary data, 1). This is
perhaps due to molecular dissymmetry, which then induces
a diastereomeric relationship. This conclusion was con-
firmed by recording the single crystal X-ray (discussed later)
and NOESY spectrum10 of 3b (Fig. 2b), which revealed the
presence of cross peaks for these protons as indicated by
arrows in Figure 2a.
(i)
O
O
O
O
O
O
O
O
R1
H
R1
R1
H
H
R1
H
No.
R1
No.
R1
R2
R3
3
4
5
6
-CH2C(O)OC2H5
-CH3
-COC6H5
-CH2C6H5
3a -CH2C(O)OC2H5
3b -CH2C(O)OC2H5
H
H
4-AP
3-AP
3-AP
3-AP
3-AP
4-NP
4-NP
3c -CH2C(O)OC2H5 3-AP
4a
-CH3
-CH3
-COC6H5
-CH2C6H5
H
3-AP
4-NP
4-NP
4b
5a
4-AP =
3-AP =
N N
N N
N
A non-diazocoupling route was also used to synthesize
azocalix[4]arene derivatives containing two free phenolic
groups. Accordingly, dibenzoylated and dibenzylated calix-
[4]arene diquinones (7, 8) were prepared by oxidation of
dibenzoylated and dibenzylated calix[4]arenes (5, 6) with
ClO2, which were treated with 4-nitro- and 2,4-dinitro-
phenylhydrazine in CHCl3/EtOH mixture in the presence
of H2SO4 to give bis(nitrophenylazophenol) derivatives in
78–84% yields. These derivatives were characterized as 5a,
6a, 7a, and 8a by spectral measurements as given in the
Section 4 (Scheme 4).
6a
N
N N
NO2
4-NP =
Scheme 3. Synthesis of dialkyl azocalix[4]arenes with two free phenolic
groups. Reagents and conditions (i) diazonium salt obtained from respective
amine, DMF/MeOH, CH3COONa, 0–5 ꢀC, 3 hr.
(a)
(b)
H
H
4
5
6
N
N
H
O
H
N
H
H
H
H
H
H
H
O
H
H
H
H
H
H
H
H
H
H
7
8
H
H
O
O
H
O
H
H
H
H
O
O
O
CH2
H2C
ppm
CH3
H3C
ppm
8
7
6
5
4
Figure 2. (a) Molecular structure of 3b and observed correlations in its NOESY spectrum; (b) correlation of aromatic and methylene protons in the NOESY
spectrum of 3b in CDCl3 at 25 ꢀC and 300 MHz.
O2N
NO2
R2
O
O
R2
N
N
N
N
i
ii
O
O
O
O
O
O
O
O
R1
R1
R1
H
R1
H
O
O
O
O
R1
R1
H
H
No.
5
R1
No.
R1
R2
No.
7
R1
-COC6H5
-CH2C6H5
5a -COC6H5
7a -COC6H5
6a -CH2C6H5
8a -CH2C6H5
H
-COC6H5
-CH2C6H5
6
-NO2
H
8
-NO2
Scheme 4. Synthesis of dialkyl azocalix[4]arenes with two free phenolic groups via a diquinone route. Reagents and conditions (i) ClO2, room temperature;
(ii) chloroform/ethanol, nitrosubstituted phenyl hydrazines, concn H2SO4, 4 h, room temperature.

H. M. Chawla et al. / Tetrahedron 62 (2006) 7854–7865
7857
(a)
(b)
O2N
NO2
ArCH2Ar
ArH
ArH
O
O
N
N
N
N
ArHquinone
O
O
O
O
O
O
ArCH2Ar
O
OH
O
HO
ArOH
O
O
1
1
Figure 3. (a) Molecular structure and H NMR spectra of dibenzoylcalix[4]diquinone 7; (b) molecular structure and H NMR spectra of 5,17-bis(40-nitro-
phenylazo)-25,27-di(benzyloxy)-26,28-dihydroxycalix[4]arene 5a.
The synthesized dibenzoylcalix[4]arene diquinones ex-
hibited characteristic methylene bridge protons as a broad
singlet in their H NMR spectrum to reveal their flexible
Since no signal was observed at around d 30, the possibility
of a partial cone conformation was not considered on the
basis of literature precedents.5
1
conformational constitution. On conversion into p-nitrophe-
nylazocalix[4]arene dibenzoyl derivative, the broad singlet
for methylene bridge protons got split into a pair of doublet
for azocalix[4]arenes (6a, 7a, and 8a) indicating that they
were present in their cone conformations (Fig. 3).
CH3
H3C
O
N
O
O
O
O
N
N
O
O
O
iii
Trimethylated-calix[4]arenes 9 (i.e., containing only one free
phenolic group) when reacted with 3 equiv of corresponding
diazonium chlorides at 0–5 ꢀC in DMF/methanol (8:5) using
sodium acetate (pH 7–9) as a base gave 9a,b.
N
N
CH3
CH3
O
O
O
O
H
H
H
H
N
1a
10a
1
Examination of the H NMR and 13C NMR spectra of tri-
Scheme 6. Synthesis of tetra-alkyl azocalix[4]arenes with one azo subs-
tituent. Reagents and conditions (iii) acetic anhydride, dichloromethane/
pyridine (10:1), room temperature, 24 h.
O-substituted azocalix[4]arenes having only one hydroxyl
group (Scheme 5, 9a, 9b) indicated that they were also pres-
ent in their cone conformation albeit the cone conformation
was flattened and deviated from its perfect cone structure as
revealed by X-ray diffraction analysis.11
When azocalix[4]arenes with two free phenolic groups pres-
ent in the cone conformation (5a–8a) were subjected to ace-
tylation in the presence of acetic anhydride and pyridine in
dichloromethane at room temperature, they gave 11a–12b
in 67–75% yield (Scheme 7), which exhibited a pair of dou-
blet in the 1H NMR spectrum (Supplementary data, 2). The
methylene carbons in 11a and 12a appeared at d 37.2 and
d 37.4, respectively, in their 13C NMR spectrum could be at-
tributed to 1,3-alternate conformations that were confirmed
by X-ray crystallographic analysis of 12a (discussed later).
R
i
O
O
O
O
O
O
O
O
CH3
H
H3C
CH3
N
CH3
H
H3C
CH3
R
9
9a
9b
N N
N N
Room temperature benzoylation of 1b with benzoyl chloride
and pyridine in dichloromethane yielded 13a (Scheme 8) in
which methylene protons appeared as a multiplet in its H
NO2
1
Scheme 5. Synthesis of azocalix[4]arenes with one free phenolic group.
Reagents and conditions (i) diazonium salt obtained from respective amine,
DMF/MeOH, CH3COONa, 0–5 ꢀC, 3 h.
NMR spectrum. The exact conformation for 13a therefore
was difficult to infer from its 1H NMR spectrum, but methyl-
ene carbons in its 13C NMR spectrum appeared as four
signals at d 37.8, 36.9, 30.2, 29.6 (Supplementary data, 3),
which were possible only if azocalix[4]arenes (13a) had a
partial cone conformation.
2.1.1. Acylation and benzoylation of azocalix[4]arenes:
conformational outcome. When 1a was reacted with acetic
anhydride and pyridine in dichloromethane at room temper-
ature, it gave 10a as a major product (Scheme 6), which ex-
hibited a singlet and a pair of doublet (1:1) for methylene
protons in its 1H NMR spectrum suggesting itto have a partial
Similarly, room temperature acylation of 2a,b with acetic
anhydride and pyridine in dichloromethane yielded 14a,b
(Scheme 9). The synthesized derivatives exhibited multi-
1
cone or 1,3-alternate conformation. This dichotomy of H
NMR spectral interpretation was resolved by the 13C NMR
spectrum (DEPT-135) in which methylene carbons appeared
at d 37.5 and 37.4 to reveal its 1,3-alternate conformation.
plets for methylene protons in their H NMR spectrum,
which made it difficult to infer exact information about the
1
conformation. However, 13C NMR spectrum (DEPT-135)

7858
H. M. Chawla et al. / Tetrahedron 62 (2006) 7854–7865
CH3
H3C
O2N
O
NO2
O
O
O
R2
R2
iii
N
N
N
N
O
O
R1
R1
N
N
N
N
R2
R2
O
O
O
O
R1
H
R1
H
NO2
NO2
No.
11a
R1
R2
H
H
-COC6H5
-CH2C6H5
-COC6H5
-CH2C6H5
11b
12a
12b
5a-8a
-NO2
-NO2
Scheme 7. Synthesis of tetra-alkyl azocalix[4]arenes with two distal azo substituents. Reagents and conditions (iii) acetic anhydride, dichloromethane/pyridine
(10:1), room temperature, 24 h.
its 13C NMR spectrum to suggest that it is present in the
1,3-alternate conformation.
N
N
N
N
N
N
O
N
O
N
N
N
N
N
O
N
O
N
N
iii
CH3
O
CH3
N
N
N
N
N
O
O
N
N
O
N
O
N
iii
N
N
N
O
O
O
O
O
N
O
O
O
N
O
O
H
H
O
H
H
O
N
N
N
O
O
N
CH3
O
CH3
H
N
H
H
H
1b
13a
N
N
1e
Scheme 8. Synthesis of tetra-alkyl azocalix[4]arenes with two proximal azo
substituent. Reagents and conditions (iii) benzoyl chloride, dichloro-
methane/pyridine (10:1), room temperature, 24 h.
15a
Scheme 10. Synthesis of tetra-alkyl azocalix[4]arenes without free phenolic
groups. Reagents and conditions (iii) acetic anhydride, dichloromethane/
pyridine (10:1), room temperature, 24 h.
of 14a revealed the presence of four signals at d 38.4, 37.8,
31.7, 30.4 for methylene carbons and three signals at d 21.2,
20.6, 20.2 for –COCH3 carbon suggesting the formation of
a partial cone conformer with one azophenol moiety near
the anisole unit in the anti disposition.
A summary of the splitting patterns observed in the 1H NMR
spectra, chemical shift values of methylene carbons in their
13C NMR spectra, and the assigned conformation of the syn-
thesized new azocalix[4]arene analogs is given in Table 1.
R
R
CH3
2.2. X-ray crystallographic analysis
R
R
R
O
O
(iii)
2.2.1. X-ray crystallographic analysis of 3b. An ORTEP
diagram of 3b is shown in Figure 4a. It appears that 3b crys-
tallizes with chloroform. The torsion angles 4 and c around
Ar—CH2—Ar bonds about C7, C14, C21, and C28 show a
ꢁ+, ꢁ+, ꢁ+, ꢁ+ pattern, which is consistent with the cone
conformation.12 The inter planer angles between ring A
(C1—C6) and its distally positioned ring C (C15—C20)
is 34.36ꢀ while the inter planer angle between ring B
(C8—C13) and D (C22—C27) is 75.90ꢀ. This suggests
that rings A and C are almost parallel while rings B and
D are almost perpendicular to each other. The azopyridyl
group has been found to be disordered. The corresponding
hydroxyl substituents O1, O2, O3, and O4 are directed in-
wards the cavity of the calixarene architecture. Both the
O2–C33–C34–O7 and O4–C29–C30–O5 are cis thereby
O
O
O
O
O
H3C
O
O
O
O
CH3
CH3
H
H3C
H
H
R
2a R= 3-AP (3-azopyridyl)
2b R= 4-NP (4-nitrophenyl azo)
14a R= 3-AP (3-azopyridyl)
14b R= 4-NP (4-nitrophenyl azo)
Scheme 9. Synthesis of tetra-alkyl azocalix[4]arenes without free phenolic
groups. Reagents and conditions (iii) acetic anhydride, dichloromethane/
pyridine (10:1), room temperature, 24 h.
Acetylation of 1e in the presence of acetic anhydride and
pyridine at room temperature resulted in 15a (Scheme 10),
which exhibited a singlet for methylene bridge protons in
1
its H NMR spectrum and methylene carbon at d 38.2 in

H. M. Chawla et al. / Tetrahedron 62 (2006) 7854–7865
7859
˚
Table 1. Conformational assignment of synthesized azocalix[n]arenes.
1H NMR splitting pattern for methylene protons and 13C NMR data for
methylene carbons (d, 300 MHz, 25 ꢀC) in different azocalix[4]arenes
(with H/p distance 3.395 A) that brings two phenyl rings
much closer thereby resulting in the formation of a dimer.
A prominent intermolecular interaction exists between the
pyridyl ring and hydrogen of the ester chain to result in a
dimeric columnar packing (Fig. 4b). These dimeric columns
run parallel and are associated with each other through
weak intermolecular hydrogen bonds (C36–H36B/N2X–¼
No
1H NMR splitting pattern
of methylene protons
(ratio of protons)
13C NMR values
for methylene
carbons
Conformation
2a
2b
3a
3b
3c
4a
Two pair of doublet (1:1:1:1) 31.2, 33.3
Two pair of doublet (1:1:1:1)
Two pair of doublet (1:1:1:1) 31.3, 29.6
Two pair of doublet (1:1:1:1) 31.3, 29.6
Cone
Cone
Cone
Cone
Cone
Cone
—
˚
2.650 A) and C–H/p interaction among C35–H35A/ring
A (with H/p distance 3.016 A). The molecular packing of
3b along the axis a is shown in Figure 4b.
˚
One pair of doublet (1:1)
One triplet and one pair of
doublet (2:1:1)
31.4
31.0, 29.5
2.2.2. X-ray crystallographic analysis of 12a. An ORTEP
diagram for 12a is shown in Figure 5a. Torsion angles 4
and c around Ar—CH2—Ar bonds about C7, C14, C21,
and C28 showing ++, ꢁꢁ, ++, ꢁꢁ are consistent with 1,3-
alternate conformation.13 The inter planar angles between
rings A (C1—C6) and its distally positioned ring C (C15—
C20) is 25.04ꢀ while between ring B (C8—C13) and D
(C22—C27) is 20.76ꢀ, which suggest that these are almost
parallel to each other. Phenyl rings of the benzoyl group
are perpendicular to the respective calixaryl aromatic ring
plane. The oxygen of the carbonyl group remains exo to the
cavity. The dihedral angle between the phenylazo group
plane(C29–C34)andringA(C1–C6)is7.41ꢀ,whichcorrobo-
rates that one phenylazo ring is parallel and the other phenyl-
azo ring (C42–C47) is perpendicular to ring C (C15—C20)
showing a dihedral angle 70.01ꢀ with the nitro group (ortho
to azo), which remains outward of the calixarene cavity.
There are prominent intramolecular C–H/p interactions
among C34–H34/Phenyl ring (C36–C41) and C47–
4b
5a
6a
7a
8a
9b
One pair of doublet (1:1)
One pair of doublet (1:1)
One pair of doublet (1:1)
One pair of doublet (1:1)
One pair of doublet (1:1)
Two pair of doublet (1:1:1:1)
31.1
32.9
—
—
—
Cone
Cone
Cone
Cone
Cone
Cone
1,3-Alternate
—
38.7, 37.5
10a One singlet and one pair of
doublet (1:1)
11a One pair of doublet
11b One pair of doublet
12a One pair of doublet
12b One pair of doublet
13a Multiplet
37.2
—
37.4
—
37.8, 36.9,
30.2, 29.6
38.4, 37.8,
31.7, 30.4
—
1,3-Alternate
1,3-Alternate
1,3-Alternate
1,3-Alternate
Partial cone
14a Multiplet
Partial cone
14b Multiplet
15a One singlet
Partial cone
1,3-Alternate
38.2
making both the carbonyl groups endo with respect to the
calix cavity.
˚
H47/Phenyl ring (C49–C54) with H/p distance 3.484 A
˚
and 3.493 A, respectively. This brings the substituted phenyl-
azo group much closer to the adjacent benzoyl ring (Fig. 5b).
The molecular packing of 12a along the axis a is shown in
Figure 5c.
A significant intramolecular hydrogen bonding has been
observed amongst hydroxyl groups and proximal oxygens
˚
˚
(O1–H1—O2¼1.939 A, O3–H3—O4¼1.970 A). There is
a prominent C–H/p interaction among C10–H10/ring A
(a)
(b)
C4X
N5X
C6X
C3X
C2X
C1X
N2X
N1
C4
C5
C3
C2
C9
C25
C6
C7
C1
C26
C28
C27
C24
C10
C11
C12
C33
C8
C23
C22
C29
C30
C13
O1
O2
O3
C20
O4
C19
C15
C14
C21
O5
C18
C16
C17
O8
C35
C36
C34
O7
O6
C31
C32
Figure 4. (a) ORTEP diagram of 3b (hydrogens, solvent molecules, and disordered part have been omitted for clarity); (b) view of the molecular packing along
the axis a.

7860
H. M. Chawla et al. / Tetrahedron 62 (2006) 7854–7865
(b) (c)
(a)
O14
O13
N8
O5
O6
N4
C45
C32
C33
C31
C30
C44
C46
C47
C43
C52
O3
O12
C34
C39
N3
C29
C51
C50
C38
C42
N7
C53
C54
C40
C41
N6
N2
N1
O4
N5
O11
C49
C37
C3
C17
C18
C36
C48 O16
C4
C35
O7
C16
C15
O8
C5
C6
C7
O15
C27
C2
C19
C28
C14
C20
C21
C26
C1
C8
C13
C12
C22
O9
O1
O2
C11
O10
C23
C25
C57
C55
C9
C24
C10
C56
C58
Figure 5. (a) ORTEP diagram showing labeling of atoms in 12a with 30% probability factor (hydrogen atoms have been omitted for clarity); (b) intermolecular
hydrogen bonds and CH–p interactions; (c) view of the molecular packing along the axis a.
3. Discussion
When free phenolic groups at the lower rim in azocalix-
arenes are completely absent, the diazo coupled product
may lead to the 1,3-alternate or partial cone conformer. It
has been determined that in such cases the 1,3-alternate con-
formation predominates particularly when the number of azo
substituents is one (Scheme 2) or when they are symmetri-
cally positioned at the upper rim (Schemes 7 and 10). How-
ever, it seems that in the event, when free phenolic groups at
the lower rim were absent and when they possess more than
two unsymmetrically positioned azo substituents (Schemes
8 and 9) at the upper rim, a partial cone conformation has
been found to be the major conformer.
The conformational flexibility of calixarene compounds has
often been explained by the presence of intramolecular hy-
drogen bonds, which is directly correlated with the number
of free phenolic hydroxyls present in the calix[4]arene. Ac-
cordingly, azocalix[4]arenes with four free phenolic groups
at the lower rim (1a–e, Scheme 1) adopt a cone conformation
in accordance with the earlier reports.14 When the number of
phenolic groups is decreased, it is apparently expected to ex-
ert a profound effect on the conformational outcome. Present
investigations however indicate that mono alkyl azocalix[4]-
arenes (2a–2d, Scheme 2) bearing three phenolic hydroxyl
groups and the dialkyl azocalix[4]arenes (3a–6a, Scheme
3) bearing two phenolic hydroxyl groups also exist in their
cone conformation.
In conclusion, we report that one can obtain the cone confor-
mation of azocalix[4]arenes if at least one free phenolic
groups present at their lower rim. 1,3-alternate and partial
cone conformations are only obtained when free phenolic
groups are absent. The conformational outcome in azoca-
lix[4]arenes is also dictated by the symmetric disposition
of azo substituent at the upper rim.
The use of an alternate route for the synthesis of azocalix[4]-
arenes with two free phenolic groups through dialkyl-
calix[4]arene diquinones, which are known to be present
in their cone and partial cone conformations in equilibrium
with each other15 also resulted in azocalix[4]arenes in their
cone conformation. This revealed that the route adopted or
the conformation of the starting material does not have
any bearing on the conformational outcome of the azoca-
lix[4]arenes.
4. Experimental
4.1. General
All the reagents used in the study were purchased from
Sigma–Aldrich or Merck and were chemically pure. The
solvents used were distilled (for diazotization reaction) and
dried(foracetylationorbenzoylationreaction).Columnchro-
matography was performed on silica gel (60–120 mesh) ob-
Examination of spectral characteristics of tri-O-substituted
azocalix[4]arenes possessing one free phenolic group
(9a,b, Scheme 5) indicate that they were also present in their
flattened cone conformation as revealed by their single
crystal X-ray diffraction analysis.11 The flattened cone con-
formation probably results because these compounds are
conformationally flexible due to loss of stabilization owing
to decreased strength of intramolecular hydrogen bonding.
Nonetheless, it is important to note that even when only one
phenolic hydroxyl is present, synthesized azocalix[4]arene is
present in the cone conformation.
1
tained from Merck. H NMR, 13C NMR, DEPT-135, and
NOESY spectra were recorded on a 300 MHz Bruker DPX
300 instrument at room temperature using tetramethylsilane
(TMS) at 0.00 as an internal standard. IR spectra were re-
´ ´
corded on a Nicolet Protege 460 spectrometer in KBr disks
while X-ray data was recorded using a Bruker SMART
CCD single crystal diffractometer. UV–vis spectra were

H. M. Chawla et al. / Tetrahedron 62 (2006) 7854–7865
7861
obtained on a Perkin–Elmer (Lambda-3B) recording spectro-
photometer. The FAB mass spectra were recorded on a JEOL
SX 102/DA-6000 Mass spectrometer/Data System using
argon/xenon (6 kV, 10 mA) as the FAB gas. Melting points
were determined on an electrothermal Toshniwal melting
point apparatus and were uncorrected.
ArH), 6.65 (br s, 1H), 4.52 (d, J¼11.7 Hz, 2H, ArCH2Ar),
4.39 (d, J¼12.6 Hz, 2H, ArCH2Ar), 3.93 (s, 3H, ArOCH3),
3.64 (d, J¼12.6 Hz, 2H, ArCH2Ar), 3.53 (d, J¼11.7 Hz,
2H, ArCH2Ar). 13C NMR (300 MHz, CDCl3): 150.3,
149.7, 148.0, 146.4, 132.0, 130.4, 129.7, 128.9, 126.4,
125.4, 124.5, 123.7, 123.1 (ArCH and ArC), 63.6 (ArOCH3),
33.5, 30.4 (ArCH2Ar). FABMS m/z: 754 (M+). Anal. Calcd
for C44H35N9O4: C, 70.11; H, 4.68; N, 16.72. Found: C,
70.35; H, 4.70; N, 16.65.
4.2. General procedure for the synthesis
p-tert-Butylcalix[4]arene and calix[4]arene were synthe-
sized by the method described by Gutsche.16 Compound
1–10 were synthesized as described in the literature17 while
1a–e and 9a were previously synthesized by our group.9,11
4.2.5. 5,11,17-Tris(40-nitrophenylazo)-25-(methoxy)-
26,27,28-trihydroxycalix[4]arene, 2b. Afforded as a red
solid. Yield: 94%, mp>200 ꢀC (decomposed). IR (KBr
pellet, cmꢁ1): 3423, 1593, 1519, 1467, 1341. 1H NMR
(300 MHz, CDCl3): d 8.35 (d, J¼8.7 Hz, 4H, NO2–ArH),
8.22 (d, J¼8.4 Hz, 2H, NO2–ArH), 7.96 (d, J¼8.7 Hz, 4H,
NO2–ArH), 7.90 (d, J¼8.4 Hz, 2H, NO2–ArH), 7.86 (s,
2H, ArH), 7.85 (s, 2H, ArH), 7.82 (s, 2H, ArH), 7.14 (d,
J¼6.9 Hz, 2H, ArHmeta), 6.91 (t, J¼6.9 Hz, 1H, ArHpara),
4.47 (t, J¼13.5 Hz, 4H, ArCH2Ar), 4.15 (s, 3H, ArOCH3),
3.77 (d, J¼13.5 Hz, 2H, ArCH2Ar), 3.67 (d, J¼13.2 Hz,
2H, ArCH2Ar). FABMS m/z: 886 (M+). Anal. Calcd for
C47H35N9O10: C, 63.73; H, 3.98; N, 14.23. Found: C,
63.58; H, 4.00; N, 14.17.
4.2.1. Synthesis of azocalix[n]arenes through the diazoti-
zation reaction (compounds 1a–e, 2a–b, 3a–c, 4a,b, 5a,
6a, 9a, 9b). The pyridyl diazonium chloride solutions were
prepared by the addition of an aqueous solution of sodium
nitrite (2 equiv of amine) into solution of respective amines
in concn HCl (10–20 equiv) and distilled water (5–10 ml) at
0–5 ꢀC. The diazotized solution was slowly added (in stan-
dardized 1.5 molar ratio with respect to each free phenolic
group in the corresponding calix[n]arenes) into an ice-cold
(0–5 ꢀC) solution of corresponding calix[n]arenes (n¼4) in
DMF/methanol (8:5), sodium acetate (pH 7–9) with constant
stirring to give yellow to dark red suspension. The reaction
mixture was stirred for 3 h at 0–5 ꢀC and then for 30 min
at room temperature. The suspension was poured into water,
acidified with concn HCl to give a yellow to dark red precipi-
tate, which was filtered to give a product or a mixture of
products. The mixture of products was then separated by
column chromatography (silica gel) to give substituted
azocalix[n]arene derivatives.
4.2.6. 5-(40-Pyridylazo)-25,27-di(ethoxycarbonyl meth-
oxy)-26,28-dihydroxycalix[4]arene, 3a. Purified by col-
umn chromatography using hexane/ethyl acetate (7:3) as
the eluent, orange solid. Yield: 10%, mp>230 ꢀC (decom-
posed). IR (KBr pellet, cmꢁ1): 3262, 1750, 1652, 1584,
1464. 1H NMR (300 MHz, CDCl3): d 8.72 (br s, 2H,
PyH), 8.56 (br s, 1H, D2O exchangeable, ArOH), 7.71 (s,
2H, ArH), 7.62 (br s, 2H, PyH), 7.57 (s, 1H, D2O exchange-
able, ArOH), 7.00 (d, J¼7.5 Hz, 2H, ArHmeta), 6.92 (d,
J¼7.5 Hz, 2H, ArHmeta), 6.89 (d, J¼7.5 Hz, 2H, ArHmeta),
6.73 (t, J¼7.5 Hz, 2H, ArHpara), 6.61 (t, J¼7.5 Hz,
1H, ArHpara), 4.75 (dd, J¼15.3, 15.9 Hz, 4H, ArOCH2),
4.50 (d, J¼13.5 Hz, 2H, ArCH2Ar), 4.39 (d, J¼13.2 Hz,
2H, ArCH2Ar), 4.32 (q, J¼6.9 Hz, 4H, –OCH2CH3), 3.48
(d, J¼13.5 Hz, 2H, ArCH2Ar), 3.37 (d, J¼12.9 Hz,
2H, ArCH2Ar), 1.32 (t, J¼7.2 Hz, 6H, –OCH2CH3).
13C NMR (300 MHz, CDCl3): 166.5, 157.9, 152.8,
152.2, 151.0, 134.5, 133.2, 129.5, 129.2, 128.8, 128.5,
127.8, 125.7, 124.7, 119.2, 116.1 (ArCH and ArC), 72.4
(ArOCH2), 61.4 (–OCH2CH3), 31.3, 29.6 (ArCH2Ar), 14.0
(–OCH2CH3). ESMS m/z: 702.61 (M++1). Anal. Calcd for
C41H39N3O8: C, 70.17; H, 5.60; N, 5.99. Found: C, 69.99;
H, 5.56; N, 5.97. UV (lmax, MeOH): 261, 379 nm.
4.2.2. Synthesis of azocalix[n]arenes through the reaction
between quinones and hydrazines (compounds 5a, 6a, 7a,
8a). To a solution of disubstituted-calix[4]arene diquinones
(7, 8) in CHCl3 was added ethanol, nitrosubstituted phenyl
hydrazines in presence of concn H2SO4. The reaction mix-
ture was stirred for 4 h at room temperature and treated
with cold water and extracted with chloroform. The organic
phasewas separatedanddriedwithsodiumsulfateand evapo-
rated in vacuo to give orange powder, which was purified by
recrystallization from chloroform/methanol.
4.2.3. Synthesis of substituted azocalix[n]arenes through
the acetylation or benzylation reaction (compounds 10a,
11a,b, 12a,b, 13a, 14a, 14b, 15a). The synthesized azoca-
lix[4]arenes (1a, 1b, 1e, 5a, 6a, 7a, 8a) and acetic anhydride
(for acetylation) or benzoyl chloride (for benzoylation)
(20 equiv) in dichloromethane/pyridine (10:1) were stirred
at room temperature for a period of 24 h. The reaction mix-
ture was poured into cold water, washed with 1 M HCl and
water, and evaporated in vacuo to give a yellow solid.
4.2.7. 5-(30-Pyridylazo)-25,27-di(ethoxycarbonyl meth-
oxy)-26,28-dihydroxycalix[4]arene, 3b. Purified by col-
umn chromatography using hexane/chloroform (6:4) as the
eluent, orange solid. Yield: 35%, mp>230 ꢀC (decomposed).
1
IR (KBr pellet, cmꢁ1): 3448, 1754, 1633, 1586, 1471. H
NMR (300 MHz, CDCl3): d 9.04 (s, 1H, PyH), 8.43 (br s,
2H, 1H–D2O exchangeable, PyH and ArOH), 7.90 (d,
J¼7.2 Hz, 1H, PyH), 7.69 (s, 2H, ArH), 7.56 (s, 1H, D2O
exchangeable, ArOH), 7.17 (dd, J¼4.5, 3.3 Hz, 1H, PyH),
6.99 (d, J¼6.9 Hz, 2H, ArHmeta), 6.84 (d, J¼7.2 Hz, 2H,
ArHmeta), 6.79 (d, J¼7.2 Hz, 2H, ArHmeta), 6.59–6.52 (m,
3H, ArHpara), 4.71 (dd, J¼15.0, 15.6 Hz, 4H, ArOCH2),
4.47 (d, J¼13.2 Hz, 2H, ArCH2Ar), 4.38 (d, J¼12.9 Hz,
2H, ArCH2Ar), 4.27 (q, J¼6.9 Hz, 4H, –OCH2CH3), 3.46
4.2.4. 5,11,17-Tris(30-pyridylazo)-25-(methoxy)-26,27,28-
trihydroxycalix[4]arene, 2a. Afforded as an orange solid.
Yield: 90%, mp>200 ꢀC (decomposed). IR (KBr pellet,
cmꢁ1): 3416, 1580, 1459, 1423. 1H NMR (300 MHz,
CDCl3, d in ppm): d 9.12 (s, 2H, PyH), 9.00 (s, 1H, PyH),
8.60 (s, 2H, PyH), 8.52 (s, 1H, PyH), 8.06 (d, J¼6.9 Hz,
2H, PyH), 7.96 (d, J¼6.9 Hz, 1H, PyH), 7.81 (s, 4H, ArH),
7.69 (s, 2H, ArH), 7.38 (br s, 3H, PyH), 6.86 (br s, 2H,

7862
H. M. Chawla et al. / Tetrahedron 62 (2006) 7854–7865
(d, J¼13.2 Hz, 2H, ArCH2Ar), 3.34 (d, J¼12.9 Hz, 2H,
ArCH2Ar), 1.28 (t, J¼6.9 Hz, 6H, –OCH2CH3). 13C NMR
(300 MHz, CDCl3): 168.6, 157.2, 152.8, 152.1, 150.4,
148.1, 146.6, 145.5, 133.0, 132.1, 130.7, 129.4, 129.1,
128.5, 127.8, 126.6, 125.6, 124.1, 123.8, 119.1 (ArCH and
ArC), 72.3 (ArOCH2), 61.4 (–OCH2CH3), 31.3, 29.6
(ArCH2Ar), 14.0 (–OCH2CH3). ESMS m/z: 702.61
(M++1). Anal. Calcd for C41H39N3O8: C, 70.17; H, 5.60;
13C NMR (300 MHz, CDCl3): 157.2, 153.1, 150.6, 148.1,
146.7, 145.7, 132.1, 129.4, 128.5, 126.6, 125.5, 124.1,
123.8 (ArCH and ArC), 63.8 (ArOCH3), 31.1 (ArCH2Ar).
FABMS m/z: 662 (M+). Anal. Calcd for C40H34N6O4: C,
72.49; H, 5.17; N, 12.68. Found: C, 72.35; H, 5.14; N,
12.62. UV (lmax, MeOH): 258, 372 nm.
4.2.11. 5,17-Bis(40-nitrophenylazo)-25,27-dibenzoyloxy-
26,28-dihydroxycalix[4]arene, 5a. Obtained as a red solid.
Yield: 78%, mp>270 ꢀC (decomposed). IR (KBr pellet,
cmꢁ1): 3500, 1729, 1655, 1595, 1518, 1461, 1343, 1262.
1H NMR (300 MHz, CDCl3): d 8.36 (d, J¼9 Hz, 4H, NO2–
ArH), 8.25 (d, J¼7.5 Hz, 4H, o-Ar0H), 7.84 (d, J¼8.7 Hz,
4H, NO2–ArH), 7.71 (s, 4H, ArH), 7.60 (m, 4H, m-Ar0H),
7.44 (t, J¼7.8 Hz, 2H, p-Ar0H), 7.12 (d, J¼7.2 Hz, 4H,
ArHmeta), 7.02 (t, J¼7.5 Hz, 2H, ArHpara), 5.98 (br s, 2H,
D2O exchangeable, ArOH), 4.07 (d, J¼14.4 Hz, 4H,
ArCH2Ar), 3.71 (d, J¼14.4 Hz, 4H, ArCH2Ar). 13C NMR
(300 MHz, CDCl3): 134.0, 133.8, 132.8, 132.0, 130.5,
130.0, 129.7, 128.9, 128.4, 126.9, 126.1, 125.2, 124.6,
123.0 (ArCH and ArC), 32.9 (ArCH2Ar). FABMS m/z: 930
(M+). Anal. Calcd for C54H38N6O10: C, 69.67; H, 4.11; N,
9.03. Found: C, 69.65; H, 4.09; N, 9.01.
N, 5.99. Found: C, 70.01; H, 5.57; N, 5.94. UV (lmax
MeOH): 263, 372 nm.
,
4.2.8. 5,17-Bis(30-pyridylazo)-25,27-di(ethoxycarbonyl
methoxy)-26,28-dihydroxycalix[4]arene, 3c. Purified by
column chromatography using CHCl3/MeOH (9.9:0.1) as
the eluent, red solid. Yield: 25%, mp>230 ꢀC (decom-
posed). IR (KBr pellet, cmꢁ1): 3374, 1730, 1601, 1466. 1H
NMR (300 MHz, CDCl3): d 9.06 (s, 2H, PyH), 8.56 (br s,
2H, PyH), 8.39 (br s, 2H, D2O exchangeable, ArOH), 8.01
(d, J¼6.9 Hz, 2H, PyH), 7.70 (s, 4H, ArH), 7.33 (dd,
J¼4.5, 3.3 Hz, 2H, PyH), 6.97 (d, J¼6.9 Hz, 4H, ArHmeta),
6.76 (t, J¼7.2 Hz, 2H, ArHpara), 4.69 (s, 4H, ArOCH2),
4.47 (d, J¼12.9 Hz, 4H, ArCH2Ar), 4.31 (q, J¼6.9 Hz,
4H, –OCH2CH3), 3.51 (d, J¼12.9 Hz, 4H, ArCH2Ar), 1.33
(t, J¼6.6 Hz, 6H, –OCH2CH3). 13C NMR (300 MHz,
CDCl3): 168.7, 157.2, 152.2, 150.5, 148.2, 146.7, 145.7,
132.4, 129.6, 128.5, 126.7, 125.9, 124.2, 123.8 (ArCH and
ArC), 72.4 (ArOCH2), 61.5 (–OCH2CH3), 31.4 (ArCH2Ar),
14.1 (–OCH2CH3). FABMS m/z: 806 (M+). Anal. Calcd for
C46H42N6O8: C, 68.47; H, 5.25; N, 10.42. Found: C, 68.35;
H, 5.20; N, 10.34. UV (lmax, MeOH): 257, 370 nm.
4.2.12. 5,17-Bis(40-nitrophenylazo)-25,27-dibenzyloxy-
26,28-dihydroxycalix[4]arene, 6a. Obtained as a red solid.
Yield: 78%, mp>240 ꢀC (decomposed). IR (KBr pellet,
cmꢁ1): 3378, 1588, 1519, 1463, 1262. 1H NMR (300 MHz,
CDCl3): d 8.62 (br s, 2H, D2O exchangeable, ArOH), 8.29
(d, J¼8.7 Hz, 4H, NO2–ArH), 7.89 (d, J¼8.7 Hz, 4H,
NO2–ArH), 7.73 (s, 4H, ArH), 7.58 (d, J¼5.4 Hz, 4H,
o-Ar0H), 7.35 (m, 6H, m-Ar0H and p-Ar0H), 6.94 (d,
J¼7.5 Hz, 4H, ArHmeta), 6.75 (t, J¼7.5 Hz, 2H, ArHpara),
5.05 (s, 4H, Ar0CH2), 4.30 (d, J¼13.2 Hz, 4H, ArCH2Ar),
3.42 (d, J¼13.2 Hz, 4H, ArCH2Ar). FABMS m/z: 902
(M+). Anal. Calcd for C54H42N6O8: C, 71.83; H, 4.69; N,
9.31. Found: C, 71.81; H, 4.67; N, 9.29.
4.2.9. 5-(30-Pyridylazo)-25,27-dimethoxy-26,28-di-
hydroxycalix[4]arene, 4a. Purified by column chromato-
graphy using CHCl3/MeOH (9.95:0.05) as the eluent,
yellow solid. Yield: 40%, mp 180 ꢀC. IR (KBr pellet,
cmꢁ1): 3274, 1653, 1590, 1470. 1H NMR (300 MHz,
CDCl3): d 9.14 (s, 1H, PyH), 8.64 (d, J¼3.6 Hz, 1H, PyH),
8.51 (br s, 1H, D2O exchangeable, ArOH), 8.09 (d,
J¼8.1 Hz, 1H, PyH), 7.78 (s, 2H, ArH), 7.76 (s, 1H, D2O
exchangeable, ArOH), 7.40 (dd, J¼4.2, 4.2 Hz, 1H, PyH),
7.10 (d, J¼7.2 Hz, 2H, ArHmeta), 6.95 (d, J¼7.2 Hz, 2H,
ArHmeta), 6.90 (d, J¼7.5 Hz, 2H, ArHmeta), 6.74–6.70 (m,
3H, ArHpara), 4.37 (t, J¼12.9 Hz, 4H, ArCH2Ar), 4.00 (s,
6H, ArOCH3), 3.57 (d, J¼13.2 Hz, 2H, ArCH2Ar), 3.44
(d, J¼13.2 Hz, 2H, ArCH2Ar). 13C NMR (300 MHz,
CDCl3): 157.2, 153.0, 150.4, 148.1, 146.6, 145.5, 132.7,
131.8, 129.3, 129.0, 128.5, 127.7, 126.5, 125.3, 124.1,
123.7, 119.1 (ArCH and ArC), 63.5 (ArOCH3), 31.0, 29.5
(ArCH2Ar). FABMS m/z: 558 (M+). Anal. Calcd for
C35H31N3O4: C, 75.38; H, 5.60; N, 7.54. Found: C, 75.25;
H, 5.58; N, 7.51. UV (lmax, MeOH): 260, 369 nm.
4.2.13. 5,17-Bis(20,40-dinitrophenylazo)-25,27-dibenzoyl-
oxy-26,28-dihydroxycalix[4]arene, 7a. Obtained as a red
solid. Yield: 84%, mp>250 ꢀC (decomposed). IR (KBr pel-
let, cmꢁ1): 3506, 1732, 1660. 1H NMR (300 MHz, CDCl3):
d 8.91 (br s, 2H, D2O exchangeable, ArOH), 8.75 (s, 2H,
NO2–ArH), 8.43 (dd, J¼2.1, 2.1 Hz, 4H, NO2–ArH), 8.23
(d, J¼7.2 Hz, 4H, o-Ar0H), 7.77 (s, 4H, ArH), 7.57 (m,
4H, m-Ar0H), 7.38 (t, J¼8.7 Hz, 2H, p-Ar0H), 7.04 (d,
J¼8.2 Hz, 4H, ArHmeta), 6.95 (t, J¼7.5 Hz, 2H, ArHpara),
4.04 (d, J¼15.3 Hz, 4H, ArCH2Ar), 3.73 (d, J¼15.3 Hz,
4H, ArCH2Ar). FABMS m/z: 1020 (M+). Anal. Calcd for
C54H36N8O14: C, 63.53; H, 3.55; N, 10.98. Found: C,
63.50; H, 3.52; N, 10.96.
4.2.10. 5,17-Bis(30-pyridylazo)-25,27-dimethoxy-26,28-
dihydroxycalix[4]arene, 4b. Purified by column chromato-
graphy using CHCl3/MeOH (9.9:0.1) as the eluent, orange
solid. Yield: 22%, mp>230 ꢀC (decomposed). IR (KBr pel-
4.2.14. 5,17-Bis(20,40-dinitrophenylazo)-25,27-dibenzyl-
oxy-26,28-dihydroxycalix[4]arene, 8a. Obtained as a red
solid. Yield: 81%, mp>280 ꢀC (decomposed). IR (KBr
pellet, cmꢁ1): 3206, 1598, 1531, 1461, 1345. 1H NMR
(300 MHz, CDCl3): d 8.93 (br s, 2H, D2O exchangeable,
ArOH), 8.76 (s, 2H, NO2–ArH), 8.50 (dd, J¼2.4, 2.4 Hz,
4H, NO2–ArH), 7.84 (d, J¼9 Hz, 4H, o-Ar0H), 7.78 (s, 4H,
ArH), 7.64 (m, 4H, m-Ar0H), 7.43 (d, J¼6.3 Hz, 2H,
p-Ar0H), 7.00 (d, J¼7.5 Hz, 4H, ArHmeta), 6.86 (t,
J¼7.2 Hz, 2H, ArHpara), 5.12 (s, 4H, Ar0CH2), 4.35 (d, J¼
13.2 Hz, 4H, ArCH2Ar), 3.53 (d, J¼13.2 Hz, 4H, ArCH2Ar).
1
let, cmꢁ1): 3382, 1630, 1586, 1473. H NMR (300 MHz,
CDCl3): d 9.14 (s, 2H, PyH), 8.64 (br s, 2H, PyH), 8.50
(br s, 2H, D2O exchangeable, ArOH), 8.10 (d, J¼7.8 Hz,
2H, PyH), 7.79 (s, 4H, ArH), 7.43 (dd, J¼4.5, 3.3 Hz, 2H,
PyH), 7.00 (d, J¼7.5 Hz, 4H, ArHmeta), 6.80 (t, J¼7.2 Hz,
2H, ArHpara), 4.37 (d, J¼13.2 Hz, 4H, ArCH2Ar), 4.03
(s, 6H, ArOCH3), 3.60 (d, J¼13.2 Hz, 4H, ArCH2Ar).

H. M. Chawla et al. / Tetrahedron 62 (2006) 7854–7865
7863
FABMS m/z: 992 (M+). Anal. Calcd for C54H40N8O12: C,
65.32; H, 4.06; N, 11.29. Found: C, 65.30; H, 4.04; N, 11.26.
ArCH2Ar), 3.70 (d, J¼15.6 Hz, 4H, ArCH2Ar), 1.94 (s.
6H, –COCH3). 13C NMR (300 MHz, CDCl3): 148.5,
134.7, 134.1, 133.4, 131.6, 126.3, 125.6, 124.9, 124.6,
123.0 (ArCH and ArC), 37.4 (ArCH2Ar), 21.2 (COCH3).
FABMS m/z: 1104 (M+). Anal. Calcd for C58H40N8O16: C,
63.04; H, 3.65; N, 10.14. Found: C, 63.01; H, 3.62; N, 10.11.
4.2.15. 5-(40-Nitrophenylazo)-25,26,27-trimethoxy-28-
hydroxycalix[4]arene, 9b. Obtained as a yellow solid.
Yield: 12%. 1H NMR (300 MHz, CDCl3): d 8.26 (d,
J¼8.7 Hz, 2H, NO2–ArH), 7.90 (d, J¼8.7 Hz, 2H, NO2–
ArH), 7.90 (d, J¼8.7 Hz, 2H, NO2–ArH), 7.73 (s, 2H,
ArH), 7.30 (d, J¼6.9 Hz, 2H, ArH), 7.11 (d, J¼6.9 Hz,
2H, ArH), 6.95–6.39 (m, 7H, ArH), 4.33 (t, J¼13.2 Hz,
4H, ArCH2Ar), 3.90 (s, 3H, OCH3), 3.79 (s, 6H, OCH3),
3.45 (d, J¼13.8 Hz, 2H, ArCH2Ar), 3.23 (d, J¼13.8 Hz,
2H, ArCH2Ar). FABMS m/z: 616 (M+). Anal. Calcd for
C37H33N3O6: C, 72.18; H, 5.40; N, 6.83. Found: C, 71.93;
H, 5.37; N, 6.76.
4.2.20. 5,17-Bis(20,40-dinitrophenylazo)-25,27-diacetyl-
oxy-26,28-benzyloxycalix[4]arene, 12b. Obtained as an
orange solid. Yield: 71%, mp>250 ꢀC (decomposed). IR
(KBr pellet, cmꢁ1): 1743, 1728, 1603, 1537, 1456, 1347.
1H NMR (300 MHz, CDCl3): d 8.85 (s, 2H, NO2–ArH),
8.56 (dd, J¼2.2, 2.2 Hz, 4H, NO2–ArH), 7.71 (s, 4H, ArH),
7.51 (d, J¼9 Hz, 4H, o-Ar0H), 7.23 (m, 6H, m-Ar0H and
p-Ar0H), 6.77 (d, J¼7.2 Hz, 4H, ArHmeta), 6.69 (t, J¼
8.7 Hz, 2H, ArHpara), 4.78 (s, 4H, Ar0CH2), 4.72 (d,
J¼10.5 Hz, 4H, ArCH2Ar), 4.64 (d, J¼10.5 Hz, 4H,
ArCH2Ar), 1.94 (s, 6H, –COCH3). FABMS m/z: 1076
(M+). Anal. Calcd for C58H44N8O14: C, 64.68; H, 4.12; N,
10.40. Found: C, 64.63; H, 4.10; N, 10.44.
4.2.16. 5(30-Pyridylazo)-25,26,27,28-tetracetyloxy-calix-
[4]arene, 10a. Obtained as a yellow solid. Yield: 72%,
1
mp>230 ꢀC (decomposed). H NMR (300 MHz, CDCl3):
d 9.16 (s, 1H, PyH), 8.73 (br s, 1H, PyH), 8.32 (d, 1H,
J¼6.9 Hz, PyH), 7.71 (s, 2H, ArH), 7.48 (br m, 1H, PyH),
7.10–6.61 (m, 9H, ArH), 3.88 (d, J¼14.1 Hz, 2H, ArCH2Ar),
3.76 (s, 4H, ArCH2Ar), 3.60 (d, J¼14.1 Hz, 2H, ArCH2Ar),
2.38 (s, 3H, –COCH3), 1.78 (s, 3H, –COCH3), 1.68 (s, 6H,
–COCH3). DEPT-135 NMR (300 MHz, CDCl3): 152.4,
147.7, 129.5, 127.3, 126.1, 125.9, 125.2, 124.4, 124.1, 119.6
(ArCH), 37.5, 37.4 (ArCH2Ar), 21.5, 20.7, 20.6 (–COCH3).
FABMS m/z: 698 (M+). Anal. Calcd for C41H35N3O8: C,
70.58; H, 5.06; N, 6.02. Found: C, 70.78; H, 5.08; N, 5.98.
4.2.21. 5,11-Bis(30-pyridylazo)-25,26,27,28-tetrabenzyl-
oxycalix[4]arene, 13a. Obtained as an orange solid. Yield:
72%, mp>230 ꢀC (decomposed). 1H NMR (300 MHz,
CDCl3): d 8.81–6.40 (m, 38H, ArH and PyH), 4.09–3.45
(m, 8H, ArCH2Ar). 13C NMR (300 MHz, CDCl3): 163.7,
152.0, 151.5, 148.1, 147.3, 146.8, 135.4, 133.8, 133.6,
133.3, 132.9, 131.3, 130.6, 129.8, 129.4, 129.1, 128.7,
128.2, 127.9, 126.9, 126.6, 126.0, 125.7, 125.0, 123.6,
122.3 (ArCH and ArC), 37.8, 36.9, 30.2, 29.6 (ArCH2Ar).
FABMS m/z: 1051 (M+). Anal. Calcd for C66H46N6O8: C,
75.42; H, 4.41; N, 8.00. Found: C, 75.25; H, 4.43; N, 8.05.
4.2.17. 5,17-Bis(40-nitrophenylazo)-25,27-diacetyloxy-
26,28-benzoyloxycalix[4]arene, 11a. Obtained as an orange
solid. Yield: 76%, mp>320 ꢀC. IR (KBr pellet, cmꢁ1): 1754,
1731, 1601, 1521, 1458, 1345. 1H NMR (300 MHz, CDCl3):
d 8.20 (d, J¼8.4 Hz, 4H, NO2–ArH), 7.58 (d, J¼7.5 Hz, 4H,
o-Ar0H), 7.40 (d, J¼8.7 Hz, 4H, NO2–ArH), 7.28 (s, 4H,
ArH), 7.12 (m, 8H, m-Ar0H and ArHmeta), 6.96 (t, J¼
7.5 Hz, 4H, p-Ar0H and ArHpara), 3.80 (d, J¼15.6 Hz, 4H,
ArCH2Ar), 3.63 (d, J¼15.6 Hz, 4H, ArCH2Ar), 2.00 (s,
6H, –COCH3). 13C NMR (300 MHz, CDCl3): 148.3, 134.5,
133.3, 132.9, 130.5, 130.2, 128.3, 125.6, 124.9, 124.4,
123.2 (ArCH and ArC), 37.2 (ArCH2Ar), 21.0 (COCH3).
FABMS m/z: 1014 (M+). Anal. Calcd for C58H42N6O12: C,
68.63; H, 4.17; N, 8.28. Found: C, 68.61; H, 4.13; N, 8.23.
4.2.22. 5,11,17-Tris(30-pyridylazo)-25,26,27-tri-acetyl-
oxy-28-methoxycalix[4]arene, 14a. Obtained as an orange
solid. Yield: 70%, mp 155 ꢀC. IR (KBr pellet, cmꢁ1): 1753,
1
1648, 1575, 1462. H NMR (300 MHz, CDCl3): d 9.25 (s,
1H, PyH), 9.17 (s, 1H, PyH), 9.06 (s, 1H, PyH), 8.75–8.67
(m, 3H, PyH), 8.21–6.66 (m, 15H, PyH and ArH), 4.17–
3.42 (m, 11H, ArCH2Ar and ArOCH3), 2.27 (s, 3H,
–COCH3), 1.85 (s, 3H, –COCH3), 1.50 (s, 3H, –COCH3).
DEPT-135 NMR (300 MHz, CDCl3): 152.3, 151.2, 147.7,
147.1, 130.6, 130.2, 128.4, 127.3, 127.0, 126.0, 125.7, 124.6,
124.4, 123.6, 120.3, 120.1 (ArCH), 61.7 (ArOCH3), 38.4,
37.8, 31.7, 30.4 (ArCH2Ar), 21.2, 20.6, 20.2 (–COCH3).
FABMS m/z: 880 (M+). Anal. Calcd for C50H41N9O7: C,
68.25; H, 4.70; N, 14.33. Found: C, 68.11; H, 4.71; N, 14.29.
4.2.18. 5,17-Bis(40-nitrophenylazo)-25,27-diacetyloxy-
26,28-benzyloxycalix[4]arene, 11b. Obtained as an orange
solid. Yield: 69%, mp 180 ꢀC. IR (KBr pellet, cmꢁ1): 1750,
1589, 1521, 1460, 1341. 1H NMR (300 MHz, CDCl3): d 8.42
(d, J¼8.1 Hz, 4H, NO2–ArH), 7.98 (d, J¼8.4 Hz, 4H, NO2–
ArH), 7.78 (s, 4H, ArH), 7.29 (m, 10H, Ar0H), 6.87 (m, 6H,
ArH), 5.08 (s, 4H, Ar0CH2), 4.80 (d, J¼12 Hz, 4H,
ArCH2Ar), 4.73 (d, J¼12 Hz, 4H, ArCH2Ar), 2.15 (s, 6H,
–COCH3). FABMS m/z: 986 (M+). Anal. Calcd for
C58H46N6O10: C, 70.58; H, 4.70; N, 8.51. Found: C, 70.56;
H, 4.67; N, 8.50.
4.2.23. 5,11,17-Tris(40-nitrophenylazo)-25,26,27-tri-ace-
tyloxy-28-methoxycalix[4]arene, 14b. Obtained as an
orange solid. Yield: 83%, mp 162 ꢀC. IR (KBr pellet,
cmꢁ1): 1756, 1595, 1522, 1462, 1342. 1H NMR (300 MHz,
CDCl3): d 8.37–6.60 (m, 21H, PyH and ArH), 4.09–3.20
(m, 11H, ArCH2Ar and ArOCH3), 2.37 (s, 3H, –COCH3),
1.91 (s, 3H, –COCH3), 1.49 (s, 3H, –COCH3). FABMS
m/z: 1012 (M+). Anal. Calcd for C53H41N9O13: C, 62.91;
H, 4.08; N, 12.46. Found: C, 62.63; H, 4.10; N, 12.38.
4.2.19. 5,17-Bis(20,40-dinitrophenylazo)-25,27-diacetyl-
oxy-26,28-benzoyloxycalix[4]arene, 12a. Obtained as an
4.2.24. 5,11,17,23-Tetrakis(30-pyridylazo)-25,26,27,28-
tetracetyloxycalix[4]arene, 15a. Obtained as an orange
solid. Yield: 92%, mp 180 ꢀC. 1H NMR (300 MHz,
CDCl3): d 9.14 (s, 4H, PyH), 8.63 (d, J¼4.2 Hz, 1H, PyH),
8.03 (d, J¼7.8 Hz, 1H, PyH), 7.68 (s, 8H, ArH), 7.39 (dd,
1
orange solid. Yield: 67%, mp>270 ꢀC (decomposed). H
NMR (300 MHz, CDCl3): d 8.62 (s, 2H, NO2–ArH), 8.36
(dd, J¼3, 3 Hz, 4H, NO2–ArH), 7.52 (s, 4H, ArH), 7.24–
6.94 (m, 16H, ArH and Ar0H), 3.83 (d, J¼15.6 Hz, 4H,

7864
H. M. Chawla et al. / Tetrahedron 62 (2006) 7854–7865
J¼4.8, 4.2 Hz, 4H, PyH), 3.92 (s, 8H, ArCH2Ar), 3.76 (s,
4H, ArCH2Ar), 3.60 (d, J¼14.1 Hz, 2H, ArCH2Ar), 1.50
(s, 12H, –COCH3). DEPT-135 NMR (300 MHz, CDCl3):
149.4, 144.6, 129.4, 126, 125.2 (ArCH), 38.2 (ArCH2Ar),
21.0 (–COCH3). FABMS m/z: 1013 (M+). Anal. Calcd for
C56H44N12O8: C, 66.40; H, 4.38; N, 16.59. Found: C,
66.63; H, 4.38; N, 16.64.
Science and Technology and Department of Biotechnology,
Govt. of India for financial assistance. We also thank Sophis-
ticated Analytical Instrumentation Facility, Central Drug
Research Institute, Lucknow for the mass spectra reported
in this paper. DST-FIST grant for single crystal X-ray facility
available at the Indian Institute of Technology, New Delhi is
thankfully acknowledged.
4.3. X-ray Structure Determination of 3b
Supplementary data
Crystal data: C41H35N3O8ꢂ2CCl3; M¼934; triclinic;
˚
˚
˚
a¼10.2509(18) A, b¼14.302(3) A, c¼14.672(3) A; a¼
Supplementary data associated with this article can be found
in the online version, at doi:10.1016/j.tet.2006.05.040.
93.644(3)ꢀ,
b¼97.642(3)ꢀ,
g¼106.115(3)ꢀ;
V¼
3
2036.7(6) A ; Z¼2; Dc¼1.427 g cmꢁ3; m¼0.381 mmꢁ1
;
˚
space group¼P1. Intensity data were collected up to q¼
47.4ꢀ by using 2q scanning mode with graphite filtered
Mo Ka radiation (l¼0.71073) on a 0.249ꢂ0.116ꢂ
0.072 mm3 crystal at 100(2) K. A total of 15,324 reflections
were measured, 7481 were independent and of which 5532
[I>2(I)] were considered observed. Final R indices
[I>2s(I)] R1¼0.0856, wR2¼0.2265, and R indices (all
data) R1¼0.1093, wR2¼0.2436 was found for 7481 observed
reflections, 0 restraints, and 605 parameters. The apparent
high R values are possibly due to the disorder found in azo-
pyridyl unit and the solvent molecules. The structure was
solved by direct methods and refined by full matrix least-
square techniques on F2 using SHELXTL. All the nonhydro-
gen atoms were refined anisotropically. C–H hydrogen atoms
were placed in geometrically calculated positions by using
a riding model. SADABS was applied for absorption correc-
tion. Torsion angles and H-bonding were calculated using
PARST. Crystal data have been deposited with the Cam-
bridge Crystallographic Data Center, under reference
CCDC 281637.
References and notes
1. (a) Gutsche, C. D. Calixarenes: Monographs in
Supramolecular Chemistry; Stoddart, J. F., Ed.; The Royal
Society of Chemistry: Cambridge, UK, 1989; (b) Gutsche,
C. D. Calixarenes Revisited: Monographs in Supramolecular
Chemistry; Stoddart, J. F., Ed.; The Royal Society of
Chemistry: Cambridge, UK, 1998; (c) Bohmer, V. Angew.
¨
Chem., Int. Ed. Engl. 1995, 34, 713; (d) Chawla, H. M.;
Srinivas, K. J. Org. Chem. 1996, 61, 8464; (e) Chawla,
H. M.; Srinivas, K. J. Chem. Soc., Chem. Commun. 1994,
2593.
2. (a) Ikeda, A.; Shinkai, S. Chem. Rev. 1997, 97, 1713; (b)
Casnati, A.; Ungaro, R.; Asfari, Z.; Vicens, J. Calixarenes
2001; Asfari, Z., Harrowfield, J., Vicens, J., Eds.; Kluwer
Academic: Dordrecht, Holland, 2001.
3. Iqbal, M.; Mangiafico, T.; Gutsche, C. D. Tetrahedron 1987, 43,
4917.
4. (a) Kim, J. Y.; Kim, G.; Kim, C. R.; Lee, S. H.; Lee, J. H.; Kim,
J. S. J. Org. Chem. 2003, 68, 1933; (b) Halouani, H.;
Bonnamour, I. D.; Duchamp, C.; Bavoux, C.; Ehlinger, N.;
Perrin, M.; Lamartine, R. Eur. J. Org. Chem. 2002, 24,
4202.
4.4. X-ray Structure Determination of 12a
Crystal data: C58H40N8O16; M¼1104.98; triclinic;
˚
˚
˚
a¼11.229(3) A, b¼14.397(4) A, c¼17.555(5) A; a¼
5. Jaime, C.; Mendoza, J. D.; Prados, P.; Nieto, P. M.; Sanchez, C.
J. Org. Chem. 1991, 56, 3372.
103.152(5)ꢀ,
b¼102.341(5)ꢀ,
g¼101.175(6)ꢀ;
V¼
3
2610.6(12) A ; Z¼2; Dc¼1.406 g cmꢁ3; m¼0.105 mmꢁ1
;
6. (a) Jianquan, L.; Rong, C.; Xiwen, H. J. Electroanal. Chem.
2002, 528, 33; (b) Jianquan, L.; Xiaoqin, T.; Xiwen, H.
J. Electroanal. Chem. 2003, 540, 111; (c) Arora, V.; Chawla,
H. M.; Francis, T.; Nanda, M.; Singh, S. P. Indian J. Chem.
2003, 42A, 3041.
7. Kao, T. L.; Wang, C. C.; Pan, Y. T.; Shiao, Y. J.; Yen, J. Y.; Shu,
C. M.; Lee, G. H.; Peng, S. M.; Chung, W. S. J. Org. Chem.
2005, 70, 2912.
8. Oueslati, I.; Abidi, R.; Amri, H.; Thuery, P.; Nierlich, M.;
Asfari, Z.; Harrowfield, J.; Vicens, J. Tetrahedron Lett. 2000,
41, 8439.
9. Chawla, H. M.; Singh, S. P.; Upreti, S. Tetrahedron 2006, 62,
2901.
˚
space group¼P1. Intensity data were collected up to q¼45ꢀ
by using 2q scanning mode with graphite filtered Mo Ka ra-
diation (l¼0.71073) on a 0.219ꢂ0.109ꢂ0.105 mm3 crystal
at 298(2) K. A total of 20,423 reflections were measured,
6806 were independent and of which 4938 [I>2(I)] were
considered observed. The structure was solved by direct
methods and refined by full matrix least-square techniques
on F2 using SHELXTL. All the nonhydrogen atoms were re-
fined anisotropically. C–H hydrogen atoms were placed in
geometrically calculated positions by using a riding model.
SADABS was applied for absorption correction. Final R in-
dices [I>2s(I)] R1¼0.0929, wR2¼0.1830, and R indices
(all data) R1¼0.1303, wR2¼0.1996 was found for 6806 ob-
served reflections, 0 restraints, and 741 parameters. Torsion
angles and H-bonding were calculated using PARST. Crystal
data have been deposited with the Cambridge Crystallo-
graphic Data Center, under reference CCDC No. 294509.
10. Markos, P. M.; Ascenso, J. R.; Segurado, M. A. P.; Pereira,
J. L. C. Tetrahedron 2001, 57, 6977.
11. Chawla, H. M.; Singh, S. P.; Upreti, S. Tetrahedron Lett.
Communicated. (CIF file of the crystal data of 9a can be
viewed from ccdc no. 281638).
12. (a) Arora, V.; Chawla, H. M.; Hundal, G. J. Chem. Crystallogr.
2004, 34, 465; (b) Ungaro, R.; Pochini, A.; Andreetti, G. D.
J. Chem. Soc., Chem. Commun. 1979, 1005; (c) Ungaro, R.;
Pochini, A.; Andreetti, G. D.; Sangermano, V. J. Chem. Soc.,
Perkin Trans. 2 1984, 12, 1979.
Acknowledgements
We thank the Council for Scientific and Industrial Research
for a senior research fellowship (to SPS) and Department of

H. M. Chawla et al. / Tetrahedron 62 (2006) 7854–7865
7865
13. Ugozzoli, F.; Andreetti, G. D. J. Inclusion Phenom. Mol.
Recognit. Chem. 1992, 13, 337.
14. (a) Aleman, C.; Casanovas, J. J. Phys. Chem. A 2005, 109,
8049; (b) Yeh, M. L.; Tang, F. S.; Chen, S. L.; Liu, W. C.;
Lin, L. G. J. Org. Chem. 1994, 59, 754.
15. (a) Beer, P. D.; Chen, Z.; Gale, P. A. Tetrahedron 1994, 50,
2938; (b) Chen, Z.; Gale, P. A.; Health, J. A.; Beer, P. D.
J. Chem. Soc., Faraday Trans. 1994, 90, 2931; (c) Beer,
P. D.; Gale, P. A.; Chen, Z.; Drew, M. G. B.; Health, J. A.;
Ogden, M. I.; Powell, H. R. Inorg. Chem. 1997, 36, 5880; (d)
Matt, D.; Steyer, S.; Allouche, L.; Hamlil, A.; Strechler, C.;
Neuburger, M. J. Mol. Struct. 2005, 740, 53.
16. (a) Gutsche, C. D. Org. Synth. 1990, 68, 234; (b) Gutsche,
C. D.; Iqbal, M.; Steward, D. J. Org. Chem. 1986, 51, 742;
(c) Hyun, K.; Gutsche, C. D. J. Org. Chem. 1982, 47, 2713.
17. (a) Shu, C. M.; Chung, W. S. J. Org. Chem. 1999, 64, 2673; (b)
Creaven, B. S.; Deasy, M.; Gallagher, J. F.; Mcginley, J.; Murry,
B. A. Tetrahedron 2001, 57, 8883; (c) Loon, J. D. V.; Arduini,
A.; Coppi, L.; Verboom, W.; Pochini, A.; Ungaro, R.; Harkema,
S.; Reinhoudt, D. N. J. Org. Chem. 1990, 55, 5639; (d) Lee,
M. D.; Yang, K. M.; Tsoo, C. Y.; Shu, C. M.; Lin, L. G.
Tetrahedron 2001, 57, 8095; (e) Gutsche, C. D.; Dhawan, B.;
Levine, J. A.; No, K. H.; Bauer, L. J. Tetrahedron 1983, 39,
409.