Synthesis of conformationally diverse tetrathiacalix[4]arene(amido)crowns and tetrathiacalix[4]arene amides with pendant amine functions

Article abstract of DOI:10.1016/j.tet.2006.07.016

A series of conformationally diverse novel tetrathiacalix[4]arene(amido)crowns and amides from tetrakis((ethoxycarbonyl)methoxy)p-tert-butyl tetrathiacalix[4]arene and its debutylated analog have been prepared by their reaction with diamines [H₂N(CH₂)_nNH₂; n=2,3,4, and 6] and polyamines. It has been determined that the length of the alkyl spacer in diamines is pivotal for the formation of either the tetrathiacalix[4]arene bis(amido)crowns or tetrathiacalix[4]arene amides with pendant amine functions. The synthesized compounds represent potential building blocks for achieving sophisticated molecular assemblies for molecular organization and recognition. Single crystal X-ray analysis of tetrathiacalix[4]arene bis(amido)crown 6a revealed that it has a 1,3-alternate conformation, which forms supramolecular complexes with chloroform.

Full text of DOI:10.1016/j.tet.2006.07.016

Tetrahedron 62 (2006) 8974–8981
Synthesis of conformationally diverse
tetrathiacalix[4]arene(amido)crowns and tetrathiacalix[4]arene
amides with pendant amine functions
*
Ananya Chakrabarti, H. M. Chawla, N. Pant, Suneel Pratap Singh and S. Upreti
*
Department of Chemistry, Indian Institute of Technology, Hauz Khas, New Delhi 110016, India
Received 1 February 2006; revised 22 June 2006; accepted 6 July 2006
Available online 28 July 2006
Abstract—A series of conformationally diverse novel tetrathiacalix[4]arene(amido)crowns and amides from tetrakis((ethoxycarbonyl)-
methoxy)p-tert-butyl tetrathiacalix[4]arene and its debutylated analog have been prepared by their reaction with diamines [H2N(CH2)nNH2;
n¼2,3,4, and 6] and polyamines. It has been determined that the length of the alkyl spacer in diamines is pivotal for the formation of either the
tetrathiacalix[4]arene bis(amido)crowns or tetrathiacalix[4]arene amides with pendant amine functions. The synthesized compounds repre-
sent potential building blocks for achieving sophisticated molecular assemblies for molecular organization and recognition. Single crystal
X-ray analysis of tetrathiacalix[4]arene bis(amido)crown 6a revealed that it has a 1,3-alternate conformation, which forms supramolecular
complexes with chloroform.
Ó 2006 Published by Elsevier Ltd.
1. Introduction
for possible applications in nuclear-waste remediation,
sensing, and radiopharmacy.
Calixamidocrowns represent a new class of synthetic molec-
ular receptors, which combine the structure and properties of
calixarenes1 and amidocrown2 compounds. The first 1,3-
calix[4]arene(amido)crown3 was synthesized and evaluated
by Reinhoudt et al. in 1991 while Bitter et al.4 reported the
synthesis of doubly bridged proximal calix[4]arene(amido)-
crown compounds through intramolecular ring closure of
chloroalkylamide precursors in 1998. Recently Samanta
et al.5 have reported N-(4-aminophthalimidoethyl)calix[4]-
amidocrown as a fluorescent sensor for iron(III) and
copper(II).
2. Results and discussion
2.1. Synthesis
Tetrathiacalix[4]arenes 1a8 and 1b9,10 were obtained by the
base catalyzed condensation of p-tert-butylphenol and sulfur
as reported previously by us and others.8–11 They were
esterified12 by reaction with bromoethylacetate in the pres-
ence of sodium carbonate and cesium carbonate in separate
reactions to give tetrathiacalix[4]arene esters 2, 3, and 4.
Compounds 2, 3, and 4 were further reacted with alkyl
diamines of varying chain lengths [NH2(CH2)nNH2; n¼2,
3,4, and 6] and a polyamine by refluxing in toluene/methanol
(1:1) in the case of 2 and 4; and THF/methanol (1:1) in the
case of 3 (Schemes 1–3) to yield tetrathiacalix[4]arene-
(amido)crowns and tetrathiacalix[4]arene amides with
pendant amine function as described in this paper.
It was envisaged that similar analogs of tetrathiacalix[4]-
arenes,6 which contain sulfur atoms in lieu of methylene
bridges in calixarenes could provide conformationally di-
verse receptors with enhanced potential for interaction with
a variety of guests. The new molecular receptors, in principle,
would offer immense possibilities for further exploration.
While our work in this area was in progress, a report7 describ-
ing the low yield synthesis of proximally bridged tetrathiaca-
lix[4]arene(amido)crown appeared, which has prompted us
to report our initial work on tetrathiacalix[4]arene(amido)-
crown derivatives with variable ring size and conformations
2.2. Characterization of products
It was observed that the reaction of 2 with 1,2-diamino-
ethane and 1,3-diaminopropane resulted in the formation
of products designated as 5a and 5b. Molecular mass deter-
mination and absence of free amino group in their spectra
(IR and NMR) revealed that both 5a and 5b were cyclic
(amido)crown compounds. The molecular ion peaks at
Keywords: Tetrathiacalix[4]arenes; Aminolysis; Amidocrowns.
* Corresponding authors. Tel.: +91 11 26591517; fax: +91 11 26591502;
e-mail addresses: hmchawla@chemistry.iitd.ernet.in; mohindrachawla@
hotmail.com
0040–4020/$ - see front matter Ó 2006 Published by Elsevier Ltd.
doi:10.1016/j.tet.2006.07.016

A. Chakrabarti et al. / Tetrahedron 62 (2006) 8974–8981
8975
i
ii
or
S
S
S
OH
S
S
NH2ZNH2
S
S
S
HO
S
S
S
S
S
S
S
S
O O
HO OH
O O
O
O
O O
O
O
O
O
O
O
O
NH
O
NH
O
NH
O
1a
O
O
Z
O
O
O
O
O
HN
HN
Z
O
O
HN
HN
NH
O
Z
Z
Z
Z
5a-b
2
H2N
NH2 NH2
H2N
5c-d
Z
Z
5a
5b
CH2CH2
CH2CH2CH2
5c CH2CH2CH2CH2
5d CH2CH2CH2CH2CH2CH2
Scheme 1. (i) Na2CO3/BrCH2COOC2H5, acetone; (ii) toluene/methanol (1:1).
Z
Z
HN
S
NH
HN
NH
O
O
O
O
O
O
O
O
O
O
O
O
O
O
S
S
S
S
S
S
S
S
S
S
S
i
ii
NH2ZNH2
or
S
S
O
O
O
O
O
O
O
O
S
S
OH
HO
1a
HO
OH
O
O
O
O
O
O
O
O
HN
NH
Z
6a-b
6c
3
Z
Z
6c -CH2CH2CH2CH2-
6a -CH2CH2-
6b -CH2CH2CH2-
Scheme 2. (i) Cs2CO3/BrCH2COOC2H5, acetone; (ii) THF/methanol (1:1).
Z
HN
NH
O
O
O
O
O
O
O
O
O
Z
O
7a
-CH2CH2-
S
S
S
S
S
S
S
S
i
ii
NH2ZNH2
7b
7c
7d
-CH2CH2CH2-
S
O
-CH2CH2CH2CH2-
-CH2CH2NHCH2CH2-
S
O
O
O
O
S
S
OH
HO
1b
HO
OH
O
O
O
O
O
HN
NH
Z
7a-d
4
Scheme 3. (i) Cs2CO3/BrCH2COOC2H5, acetone; (ii) toluene/methanol (1:1).
1001 [M+] and 1029 [M+] for 5a and 5b, respectively, in the
FABMS spectrum confirmed the formation of tetrathia-
calix[4]arene bis(amido)crowns. Since the formation of
tetrathiacalix[4]arene(amido)crowns could in principle
encompass the ester functionalities at either the proximal
positions (a,b and c,d) or the distal positions (a,c and b,d)
(Fig. 1), the issue was resolved by NMR experiments. For
S
S
S
S
S
c
S
c
S
S
O d
bO Od
b
O
aO
a
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
1
instance, the H NMR spectrum of 5a exhibited a pair of
(a)
(b)
doublets for the ArOCH2 protons at d 3.97 and 5.09 to reveal
the non-equivalence of the geminal protons attached to the
phenolic function of tetrathiacalix[4]arene. A similar pattern
Figure 1. Possibility of (amido)crown formation by utilizing ester groups at
(a) a, b and c, d and (b) a, b and c, d.

8976
A. Chakrabarti et al. / Tetrahedron 62 (2006) 8974–8981
f
f
Hb'
Hb
Hc
S
S
S
S
S
S
S
S
O O
O
O
O
N
O O
O
O
N
Hc
Hf
d
O
NH
O
NH
O
NH
O
O
NH
*
O
O
Hc'
Ha
NH
Hd
HN
e
Ha
e''
e'''
H2N
e
He, He′
Hd'
e'
H ,
Hb, Hb′
Hc′
c
H2N
H2N
Hb
H2N
H
Hd,
Hf
b
d′
Ha
He
He′′, He′′′
Hd
*
Hc
Ha
*
ppm
10
8
6
4
2
0
10
8
6
4
2
0
Figure 2. 1H NMR spectrum of 5b.
Figure 3. 1H NMR spectrum of 5c.
for ArOCH2 protons was observed for 5b with a pair of
doublets at d 4.69 and 4.93 (Fig. 2). It was evident that the
ArOCH2 protons would be non-equivalent only if the tetra-
thiacalix[4]arene(amido)crownformationtakesplacebycon-
densation with the ester groups present at proximal positions.
In the event that the tetrathiacalix[4]arene(amido)crown
formation had involved the distal groups, the ArOCH2 pro-
tons would appear as a singlet due to magnetic equivalence.
exchanged with deuterium when shaken with D2O. This indi-
cated the presence of two types of NH protons, which could
be attributed to the –CH2CH2CH2CH2NH2 and ArOCH2-
CONHCH2 protons, respectively. Thus, 5c could be identi-
fied as tetrathiacalix[4]arene amide with pendant amine
functions. This was further supported by the [M+] peak at
1233 observed in its FABMS spectrum. Compound 5d also
revealed similar 1H NMR and mass spectral patterns.
The appearance of one signal for the tert-butyl groups and
two singlets in the aromatic region at 7.29 and 7.32 ppm in
the case of 5a and at 7.38 and 7.40 ppm for 5b suggested
that the synthesized compounds might possibly exist as prox-
imally substituted cyclic amides with a cone or 1,2-alternate
conformation of the tetrathiacalixarene core. The possibility
of a 1,2-alternate conformation of tetrathiacalix[4]arene was
excluded with the help of a NOESY spectrum. No correlation
was found between the tert-butyl groups and the amide func-
tion. When 2 was reacted with higher diamines (1,4-diamino-
butane and 1,6-diaminohexane), it gave new compounds 5c
When tetraester 3 was subjected to aminolysis with diamines
containing varying spacer lengths, it yielded a series of com-
pounds 6a–c. The products 6a and 6b exhibited rather sim-
ple 1H NMR spectra with one singlet each for the ArOCH2,
the aromatic, and the tert-butyl protons (Fig. 4). This could
be attributed to the highly symmetric nature of the tetrathia-
calix[4]arene bis(amido)crown compounds. The 1,3-alter-
nate conformation of 6a was unequivocally proved by its
single crystal X-ray diffraction analysis (see Section 2.3).
1
1
and 5d. The H NMR spectrum of 5c (Fig. 3) revealed the
The H NMR spectrum of 6c exhibited a deuterium ex-
appearance of a broad singlet for the ArOCH2 protons at
4.79 ppm along with singlets at d 7.36, 8.16, and 8.29 as
depicted in Figure 3. The broad singlets at d 8.16 and 8.29
changeable broad triplet for the ArOCH2CONHCH2 protons
at d 5.83, which integrated for two protons suggesting the
formation of two amide linkages. Absence of signals for
NH HN
O
O
O
O
S
S
S
S
O
O
Ha
c
e
O
He
O
Hb
N
HN
Ha
Hc
d
Hd
Hb
*
ppm
8
6
4
2
Figure 4. 1H NMR spectrum of 6a.

A. Chakrabarti et al. / Tetrahedron 62 (2006) 8974–8981
(a)
8977
the –NH2 protons suggested the possibility of formation of
tetrathiacalix[4]arene mono(amido)crown derivative. Two
broad signals at d 3.19 and 1.09 for the CONHCH2CH2
and the CONHCH2CH2 protons, respectively, indicated the
formation of tetrathiacalix[4]arene mono(amido)crown
with the possibility of two uncondensed ester groups in 6c.
A quartet at d 4.11 for the OCH2CH3 protons integrating
for two protons and a triplet for three protons at d 1.19 for
the OCH2CH3 protons suggested the presence of only one
ethyl ester group. However, a singlet at d 3.65 integrating
NH HN
O
O
O
O
*
S
S
S
S
Hc
Ha′
O
O
Ha
Hd
Ha'
O
Hb
c
O
N
HN
1
for three protons in its H NMR spectrum and a signal at
Ha
Hb
d
d 51 for OCH3 carbon in DEPT-135 spectrum suggested
that one methyl ester function was present in 6c. This was
confirmed by the appearance of three signals for the ArOCH2
protons at d 4.45, 4.43, and 4.39 in the ratio of 2:1:1 in the
1H NMR spectrum of 6c (Fig. 5).
ppm 10
HN
8
6
4
2
0
(b)
Though the products obtained in the reaction of 3 with 1,6-
diaminohexane and diethylene triamine could not be fully
characterized due to their insolubility in common solvents,
it could be inferred on the basis of solubility characteristics
and Rf values that bis(amido)crowns were not present in the
reaction mixture.
NH HN
O
O
O
O
S
S
S
S
O
O
When the debutylated tetraester 4 was subjected to amino-
lysis with diamines with varying spacer lengths, it yielded
a series of compounds 7a–d. All these compounds exhibited
a rather simple pattern of 1H NMR spectra with one doublet
and one triplet for the aromatic protons and one singlet for
the ArOCH2 protons (Fig. 6), suggesting a highly symmetric
nature for 7a–d. A deuterium exchangeable broad triplet in-
tegrating for four NH protons suggested the presence of four
amide linkages in the tetrathiacalix[4]arene core. Absence of
signals for the NH2 protons, the proton integration for the
methylene groups present in the corresponding spacer
chain as well as FAB mass spectrometric analysis confirmed
that the compounds in hand were tetrathiacalix[4]arene
bis(amido)crowns.
Ha
Ha'
c
*
Hc
Ha′
O
O
Hd
N
d
HN
Hb
Hd′
d'
N
Hb
Hb′
Hb'
Ha
ppm
8
6
4
2
0
Figure 6. 1H NMR spectra of (a) 7a and (b) 7e. * Indicates residual solvent
peak or water peak.
f '
f
Hb
N
HN
g''
O
O
g'
c
H
Ha'
S
a''O
O
S
S
S
O
O
O
Ha
c''
c'
g
Hg, Hg′, Hg′′, Hh
O
O
O
h
d
CH3
e
Hc, Hc′, Hc′′
He
Hf
Ha, Ha′, Ha′′
Hf ′
*
Hb
Hd
*
ppm
8
6
4
2
0
Figure 5. 1H NMR spectrum of 6c.

8978
A. Chakrabarti et al. / Tetrahedron 62 (2006) 8974–8981
Figure 7. (a) X-ray structure of 6a and (b) crystal packing of 6a along a axis showing unit cell having four tetrathiacalix[4]arene molecules (hydrogen atoms
have been omitted for clarity).
2.3. X-ray crystallographic analysis of 6a
of the condensing diamines plays an important role in their
reaction with tetrathiacalix[4]arene esters. Accordingly, the
reaction when carried out with a diamine with a larger spacer
unit (e.g., 1,6-diaminohexane) gives the 5,11,17,23-tetra-
tert-butyl-25,26,27,28-tetrakis[((N-6-aminohexyl)aminocar-
bonyl)-methoxy]tetrathiacalix[4]arene in appreciable yields.
A definitive proof for the geometry of 6a was obtained by sin-
gle crystal X-ray analysis (Fig. 7a). Colorless crystals of 6a
with space group I-4 were obtained by slow evaporation of
a chloroform solution. The torsion angles at the sulfur bridges
revealed a sequence of ++, ꢀꢀ, ++, ꢀꢀ that is consistent
with the 1,3-alternate conformation found in calix[4]arene13
and tetrathiacalix[4]arene derivatives.14 The average dis-
tances between two adjacent and two opposite sulfur atoms
It is known that tetrathiacalix[4]arene tetraesters in their 1,3-
alternate conformation1 possess larger annuli (i.e., a greater
distance between the distal ester moieties) than their cone
counterparts. They are therefore expected to require larger
diamino components to curtail mobility as compared to the
cone conformers and should therefore yield different results
on their condensation with diamines of varying spacer
lengths. Thus, the 1,3-alternate conformation of p-tert-butyl
thiacalix[4]arene tetraethylester 3 when reacted with 1,2-di-
aminoethane and 1,3-diaminopropane, yields bis(amido)-
crowns in good yields. However, the reaction with 1,4-
diaminobutane, even when refluxing is continued for seven
days, provides a mixture, which on purification by column
chromatography gives p-tert-butyl tetrathiacalix[4]arene
mono(amido)crown (6c) with two unreacted ester moieties.
˚
are 5.58 and 7.76 A, respectively, while the typical distances
between the corresponding CH2 groups in 1,3-alternate
˚
calix[4]arene are 5.0 and 7.1 A. This indicated that the cavity
of tetra-tert-butyl tetrathiacalix[4]arenes is bigger than the
classical tetra-tert-butylcalix[4]arenes. The unit cell of 6a
consists of four thiacalix[4]arene molecules, eight chloro-
form, and eight water molecules (Fig. 7b). The distance of
˚
the two distal rings ranges from 5.28 A (lower rim) to
ꢁ
˚
7.94 A (upper rim) with an inclination angle of around 54 .
All the four amido chains have their carbonyl groups exo
with respect to the thiacalix[4]arene cavity. The hydrogen
of the amide group is endo to the thiacalix[4]arene cavity
and is not involved in intra or intermolecular hydrogen bond-
ing. Each chloroform molecule is intermolecularly hydrogen
bonded to the bridging sulfur atom of one thiacalix[4]arene
molecule and the carbonyl oxygen of the other thiacalix[4]-
arene molecule. These intermolecular interactions between
tetrathiacalix[4]arene and chloroform molecules lead to the
formation of supramolecular aggregates with large cavities
as depicted in Figure 7b.
The formation of 6c is interesting in this reaction as it indi-
cates that there is a competition between the solvent and the
diamines used. The basic diamine promotes the methanoly-
sis of one of the ester functions in tetra-tert-butyl tetrathia-
calix[4]arene to yield 6c. This point is currently being
investigated in our laboratories. This presumably leads to
a change in the 1,3-alternate conformation in such a way
that further reaction is hindered.
2.4. Discussion
The aminolysis reaction of the debutylated analog of
tetrathiacalix[4]arene, 4, with 1,2-diaminoethane and 1,3-
diaminopropane yielded the tetrathiacalix[4]arene bis-
(amido)crowns in good yields (81–85%) while its reaction
with 1,4-diaminobutane and diethylene triamine gave tetra-
thiacalix[4]arene bis(amido)crowns in low yields (8–15%).
The better yields of the cyclized tetrathiacalix[4]arene 1,3-
bis(amido)crowns (7a, 7b) in comparison to their p-tert-
butyl tetrathiacalix[4]arene analogs could be attributed to
It has been observed that the reaction of 2 with ethylene and
propylene diamines proceeds smoothly to result in the forma-
tion of proximally bridged tetrathiacalix[4]arene(amido)-
crowns, 5a and 5b. When the reaction is carried out with
1,4-diaminobutane, it does not provide proximally bridged
(amido)crown compounds as expected but instead provides
a tetrathiacalix[4]arene amide with pendant primary amine
functionality. This implies that the length of the alkyl chain

A. Chakrabarti et al. / Tetrahedron 62 (2006) 8974–8981
8979
steric crowding due to the neighboring tert-butyl groups and
the aromatic rings in the latter series of compounds. It has
been observed that the absence of p-tert-butyl groups in
the tetrathiacalix[4]arenes allows them to enjoy greater con-
formational mobility to react with larger diamines to provide
tetrathiacalix[4]arene bis(amido) crowns even with 1,4-
diaminobutane and diethylene triamine (7c, 7e) but the
same has not been observed in the case of p-tert-butyl
tetrathiacalix[4]arene esters.
pure to be used without further purification. The solvents
used were distilled. Melting points were recorded on an elec-
tric melting point apparatus (Toshniwal, India) and are un-
ꢀ ꢀ
corrected. IR spectra were recorded on a Nicolet Protege
460 spectrometer in KBr discs while CHN analyses were ob-
tained by using a Perkin–Elmer 240C elemental analyzer. 1H
NMR spectra were recorded on a 300 MHz Bruker DPX 300
instrument at room temperature using tetramethylsilane
(TMS) as an internal standard. 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.
It is worth mentioning that Lhotak et al.7 have recently syn-
thesized bis(amido)crowns with ethylene, propylene, and
butylene spacer groups under different reaction conditions
(refluxing in ethanol, 16 h) in 36, 19, and 9% yields, respec-
tively, as against our conditions, which involve refluxing of
reactants in a mixture of toluene and methanol for 24 h,
which gave significantly different results. In our experi-
ments, toluene was used to solubilize 2 and 4 while methanol
under basic conditions leads to trans esterification of ethyl
ester group to provide a more reactive methyl ester, which
apparently facilitates the aminolysis reaction to allow isola-
tion of tetrathiacalix[4]arene bis(amido)crown compounds
5a and 5b in 71 and 69% yields, respectively. Tetrathiaca-
lix[4]arene bis(amido)crowns with a butylene spacer group
could not be obtained under these conditions, which allowed
the isolation of 5,11,17,23-tetra-tert-butyl-25,26,27,28-tet-
rakis[((N-4-aminobutyl)aminocarbonyl)-methoxy]tetrathia-
calix[4]arene (5c) in 83% yield. Since 3 was not completely
soluble in toluene/methanol, an alternative solvent system
(THF/methanol) was used in this case.
3.2. Preparation of the starting materials
p-tert-Butyl tetrathiacalix[4]arene8 (1a) and tetrathiaca-
lix[4]arene9 (1b) were synthesized by methods reported ear-
lier. The tetra acetates 2, 3, and 4 were synthesized by the
method10 reported in the literature, which involved the use
of ethylbromoacetate and acetone/M2CO3 system (M¼Na
and Cs) for effecting the condensation reactions.
3.3. General procedure for the synthesis of tetrathia-
calix[4]arene amides
A mixture of tetrathiacalix[4]arene tetraethylacetate (0.5 g,
0.493 mmol) and diamine (9.86 mmol) was refluxed in tolu-
ene/methanol (1:1) (30 mL) or THF/methanol (1:1) (30 mL).
After removing the solvents, the crude mixture was precipi-
tated with methanol to provide compounds, which were
purified either by crystallization from appropriate solvents
or by column chromatography.
It has been observed that the alkyl spacer group of the di-
amine plays a greater role in the aminolysis reaction of tet-
rathiacalix[4]arene tetraesters as compared to that of their
calix[4]arene analogs, which provide the proximally bridged
calix[4]arene amidocrown compounds even with larger
spacer units (1,4-diaminobutane, diethylene triamine, and
triethylene tetramine). The aminolysis reaction of the cone
conformers of tetrathiacalix[4]arene esters with higher di-
amines (1,4-diaminobutane and 1,6-diaminohexane) gave
tetrakis[(alkyl)aminocarbonyl-methoxy]tetrathiacalix[4]-
arene amides with pendant amine functionality. The 1,3-alter-
nate conformer of tetrathiacalix[4]arene tetraethylacetate,
however, gave tetrathiacalix[4]arene bis(amido)crown de-
rivatives in their 1,3-alternate conformation to pave the
way for obtaining molecular capsules.
3.3.1. (a,b;c,d)-5,11,17,23-Tetra-tert-butyl tetrathia-
calix[4]arene(ethyleneamido)biscrown, 5a. White solid
recrystallized from CHCl3/MeOH (0.35 g, 71%), mp
240 ꢁC (dec). IR (KBr, n/cmꢀ1): 3335, 1677. Anal. Calcd
for C52H64N4O8S4: C, 62.37; H, 6.44; N, 5.60. Found: C,
1
62.48; H, 6.40; N, 5.58. H NMR (300 MHz, CDCl3) dH
8.34 (br s, 4H, CONH), 7.32 (s, 4H, ArH), 7.29 (s, 4H,
ArH), 5.09 (d, J¼13.8 Hz, 4H, ArOCH2), 3.97 (d,
J¼13.8 Hz, 4H, ArOCH2), 3.63 (br s, 4H, CONHCH2),
3.51 (br s, 4H, CONHCH2), 1.05 (s, 36H, C(CH3)3),
FABMS: calcd for C52H64N4O8S4: m/z¼1001.35 [M+];
found: m/z¼1001 [M+, 100%].
3.3.2. (a,b;c,d)-5,11,17,23-Tetra-tert-butyl tetrathia-
calix[4]arene(propyleneamido)biscrown, 5b. White solid
recrystallized from CHCl3/MeOH (0.35 g, 69%), mp
266 ꢁC (dec). IR (KBr, n/cmꢀ1): 3334, 1676. Anal. Calcd
for C54H68N4O8S4: C, 63.01; H, 6.66; N, 5.44. Found: C,
In conclusion, a new strategy has enabled the synthesis of
conformationally diverse tetrathiacalix[4]arene(amido)-
crown compounds of different sizes. These could serve as
building blocks for the synthesis of larger and more sophis-
ticated molecular assemblies and molecular capsules of
tetrathiacalix[4]arene(amido)crowns in the 1,3-alternate
conformation thereby opening up a new dimension to tetra-
thiacalix[4]arene(amido)crown chemistry.
1
62.91; H, 6.72; N, 5.48. H NMR (300 MHz, CDCl3) dH
7.84 (br s, 4H, CONH), 7.40 (s, 4H, ArH), 7.38 (s, 4H,
ArH), 4.93 (d, J¼14.6 Hz, 4H, ArOCH2), 4.69 (d,
J¼14.6 Hz, 4H, ArOCH2), 3.67 (br s, 4H, CONHCH2),
3.52 (br s, 4H, CONHCH2), 1.96 (m, 4H, CONHCH2CH2),
1.12 (s, 36H, C(CH3)3), FABMS: calcd for C54H68N4O8S4:
m/z¼1029.40 [M+]; found: m/z¼1029 [M+, 100%].
3. Experimental
3.1. General
3.3.3. 5,11,17,23-Tetra-tert-butyl-25,26,27,28-tetrakis
[((N-4-aminobutyl)aminocarbonyl)-methoxy]tetrathia-
calix[4]arene, 5c. White solid recrystallized from MeOH/
H2O (0.51 g, 83%), mp 268 ꢁC. IR (KBr, n/cmꢀ1): 3414,
All the reagents used in the study were purchased from
Sigma–Aldrich or Merck and were considered chemically

8980
A. Chakrabarti et al. / Tetrahedron 62 (2006) 8974–8981
1676. Anal. Calcd for C64H96N8O8S4: C, 62.30; H, 7.84; N,
9.08. Found: C, 62.42; H, 7.76; N, 9.10. 1H NMR (300 MHz,
DMSO-d6 ) dH 8.29 (br s, 4H, CONH), 8.16 (br s, 8H,
CH2NH2), 7.36 (s, 8H, ArH), 4.79 (s, 8H, ArOCH2), 3.21
(m, 8H, CONHCH2), 2.80 (m, 8H, CH2NH2), 1.64 (m,
16H, NHCH2CH2CH2), 1.08 (s, 36H, C(CH3)3), FABMS:
calcd for C64H96N8O8S4: m/z¼1233.76 [M+]; found:
m/z¼1233 [M+, 100%].
51.2 (–OCH3), 37.1 (–CONHCH2), 31.1, 30.8 (Ar-C-CH3),
25.8 (–CONHCH2CH2), 14.1 (–CO(O)CH2CH3), FABMS:
calcd for C55H70N2O10S4: m/z¼1047.41 [M+]; found:
m/z¼1047 [M+, 100%].
y
3.3.8. (a,c;b,d)-Tetrathiacalix[4]arene(ethyleneamido)-
biscrown, 7a. White solid recrystallized from CHCl3/
MeOH (0.393 g, 85%), mp 307 ꢁC (dec). IR (KBr, n/cmꢀ1):
3414, 1686. Anal. Calcd for C36H32N4O8S4: C, 55.65; H,
1
3.3.4. 5,11,17,23-Tetra-tert-butyl-25,26,27,28-tetrakis
[((N-6-aminohexyl)aminocarbonyl)-methoxy]tetrathia-
calix[4]arene, 5d. White solid recrystallized from MeOH/
H2O (0.53 g, 81%), mp 130 ꢁC. IR (KBr, n/cmꢀ1): 3339,
1642. Anal. Calcd for C72H112N8O8S4: C, 64.25; H, 8.39;
N, 8.33. Found: C, 64.36; H, 8.36; N, 8.38. 1H NMR
(300 MHz, CDCl3) dH 7.34 (s, 8H, ArH), 5.83 (br s, 4H,
CONH), 5.30 (br s, 8H, CH2NH2), 4.82 (s, 8H, ArOCH2),
3.36 (br s, 8H, CONHCH2), 2.69 (br s, 8H, CH2NH2),
1.60–1.33 (m, 32H, NHCH2(CH2)4), 1.11 (s, 36H, C(CH3)3),
FABMS: calcd for C72H112N8O8S4: m/z¼1345.97 [M+];
found: m/z¼1346 [M+, 100%].
4.15; N, 7.21. Found: C, 55.59; H, 4.09; N, 7.26. H NMR
(300 MHz, CDCl3) dH 7.49 (d, J¼7.7 Hz, 8H, ArH), 7.07
(t, J¼15.5 Hz, 4H, ArH), 5.11 (s, 4H, CONH), 4.65 (s, 8H,
ArOCH2), 3.12 (s, 8H, CONHCH2), FABMS: calcd for
C36H32N4O8S4: m/z¼776.92 [M+]; found: m/z¼777 [M+,
100%].
3.3.9. (a,c;b,d)-Tetrathiacalix[4]arene(propyleneamido)-
biscrown, 7b. White solid recrystallized from CHCl3/
MeOH (0.388 g, 81%), mp 308 ꢁC (dec). IR (KBr, n/cmꢀ1):
3415, 1688. Anal. Calcd for C38H36N4O8S4: C, 56.70; H,
1
4.61; N, 6.96. Found: C, 56.58; H, 4.68; N, 6.91. H NMR
(300 MHz, CDCl3) dH 7.47 (d, J¼7.7 Hz, 8H, ArH), 7.05
(t, J¼15.4 Hz, 4H, ArH), 5.09 (br s, 4H, CONH), 4.62
(s, 8H, ArOCH2), 3.24 (m, 8H, CONHCH2), 1.71 (br s,
4H, NHCH2CH2), FABMS: calcd for C38H36N4O8S4:
m/z¼804.97 [M+]; found: m/z¼805 [M+, 95%].
3.3.5. (a,c;b,d)-5,11,17,23-Tetra-tert-butyl tetrathia-
calix[4]arene(ethyleneamido)biscrown, 6a. White solid
recrystallized from CHCl3/MeOH (0.32 g, 65%), mp
297 ꢁC (dec). IR (KBr, n/cmꢀ1): 3410, 1688. Anal. Calcd for
C52H64N4O8S4: C, 62.37; H, 6.44; N, 5.61. Found: C, 62.26;
H, 6.52; N, 5.58. 1H NMR (300 MHz, CDCl3) dH 7.40 (s, 8H,
ArH), 5.44 (br s, 4H, CONH), 4.40 (s, 8H, ArOCH2), 3.05
(br s, 8H, CONHCH2), 1.28 (s, 36H, C(CH3)3), FABMS:
calcd for C52H64N4O8S4: m/z¼1001.35 [M+]; found:
m/z¼1001 [M+, 100%].
3.3.10. (a,c;b,d)-Tetrathiacalix[4]arene(butyleneamido)-
biscrown, 7c. White solid recrystallized from CHCl3/
MeOH (0.039 g, 8%), mp 310 ꢁC (dec). IR (KBr, n/cmꢀ1):
3418, 1686. Anal. Calcd for C41H42N4O7S4: C, 59.25; H,
1
5.09; N, 6.74. Found: yC, 59.38; H, 5.11; N, 6.79. H NMR
(300 MHz, DMSO-d6 ) dH 7.48 (d, J¼7.7 Hz, 8H, ArH),
7.04 (t, J¼15.4 Hz, 4H, ArH), 5.04 (s, 4H, CONH), 4.60
(s, 8H, ArOCH2), 3.24 (m, 8H, CONHCH2), 1.71 (br s,
4H, NHCH2CH2), FABMS: calcd for C41H42N4O7S4:
m/z¼831.05 [M+]; found: m/z¼831 [M+, 95%].
3.3.6. (a,c;b,d)-5,11,17,23-Tetra-tert-butyl tetrathia-
calix[4]arene (propyleneamido)biscrown, 6b. White solid
recrystallized from CHCl3/MeOH (0.30 g, 61%), mp 307 ꢁC
(dec). IR (KBr, n/cmꢀ1): 3415, 1685. Anal. Calcd for
C54H68N4O8S4: C, 63.01; H, 6.66; N, 5.44. Found: C,
1
63.09; H, 6.69; N, 5.51. H NMR (300 MHz, CDCl3) dH
3.3.11. (a,c;b,d)-Tetrathiacalix[4]arene(diethylenetri-
aminoamido)biscrown, 7d. White solid recrystallized
from CHCl3/MeOH (0.077 g, 15%), mp 315 ꢁC (dec). IR
(KBr, n/cmꢀ1): 3409, 3272, 1657. Anal. Calcd for
C40H42N6O8S4: C, 53.58; H, 4.25; N, 10.41. Found: C,
7.39 (s, 8H, ArH), 5.46 (s, 4H, CONH), 4.33 (s, 8H, Ar-
OCH2), 3.11 (br s, 8H, CONHCH2), 1.66 (br s, 4H,
CONHCH2CH2), 1.28 (s, 36H, C(CH3)3), FABMS: calcd
for C54H68N4O8S4: m/z¼1029.40 [M+]; found: m/z¼1029
[M+, 100%].
1
53.42; H, 4.36; N, 10.28. H NMR (300 MHz, CDCl3) dH
7.50 (d, J¼7.3 Hz, 8H, ArH), 6.88 (t, J¼14.7 Hz, 4H,
ArH), 6.29 (s, 4H, CONH), 4.64 (s, 8H, ArOCH2), 3.62
(br s, 8H, CONHCH2CH2), 3.49 (br s, 2H, CH2NHCH2),
2.89 (br s, 8H, CONHCH2CH2), FABMS: calcd for
C40H42N6O8S4: m/z¼863.06 [M+]; found: m/z¼863 [M+,
100%].
3.3.7. (a,c)-5,11,17,23-Tetra-tert-butyl tetrathiacalix[4]-
arene(butyleneamido)monocrown, 6c. White solid puri-
fied by column chromatography (9.6:0.4 chloroform/ethyl
actetate, Rf ¼ 0.46) (0.17 g, 33%), mp 210 ꢁC (dec). IR
(KBr, n/cmꢀ1): 3403, 1769, 1737, 1682. Anal. Calcd for
C55H70N2O10S4: C, 63.07; H, 6.74; N, 2.67. Found: C,
1
63.19; H, 6.78; N, 2.61. H NMR (300 MHz, CDCl3) dH
3.4. X-ray crystallography
7.41 (d, J¼5.2 Hz, 2H, ArH), 7.39 (d, J¼5.8 Hz, 2H, ArH),
7.25 (s, 4H, ArH), 5.83 (s, 2H, CONH), 4.45 (s, 4H, Ar-
OCH2), 4.44 (s, 2H, ArOCH2), 4.39 (s, 2H, ArOCH2), 4.11
(q, J¼21.2 Hz, 2H, OCH2CH3), 3.65 (s, 3H, OCH3), 3.19
(br s, 4H, NHCH2CH2), 1.24 (s, 36H, C(CH3)3), 1.19 (t,
J¼13.9 Hz, 3H, OCH2CH3), 1.09 (br s, 4H, CONHCH2CH2).
DEPT-135 (75 MHz, CDCl3) d 131.2, 130.9, 125.5 (aromatic
CH), 69.2, 64.8, 64.4, 64.2 (Ar-OCH2 & –CO(O)CH2CH3),
Crystals suitable for single crystal X-ray diffraction were ob-
tained by slow cooling of a warm solution of 6a, in chloro-
form, having molecular formula C56H64Cl12N4O12S4,
M¼1538.75, tetragonal, space group I-4 with a¼15.251(3),
b¼15.251(3), c¼16.342(4), a¼90.0, b¼90.0, g¼90.0ꢁ,
and Dc¼1.344 g/cm3 for Z¼2. Intensity diffraction data
were calculated up to q¼20.50ꢁ by using 2u step scanning
˚
mode with Mo Ka radiation (l¼0.71073 A) at 298 K. A total
y
of 3343 reflections were calculated and used in structure
analysis and refinement. All the non-hydrogen atoms were
5c and 7c were not completely soluble even in DMSO-d6, hence they were
solubilized by heating with NaCl.

A. Chakrabarti et al. / Tetrahedron 62 (2006) 8974–8981
8981
Takemura, H.; Nakamichi, H.; Sako, K. Tetrahedron Lett.
2005, 46, 2063–2066.
3. Ostaszewski, R.; Stevens, T. W.; Verboom, W.; Reinhoudt,
D. N. Recl. Trav. Chim. Pays-Bas 1991, 110, 294–298.
refined anisotropically using restraints on the bond lengths
and thermal parameters. All hydrogen atoms were placed
in their geometrical positions and were not refined. Using
observed data and refinement of 203 parameters with no
restraints, the final R index was Rall¼0.0924, Rgt¼0.0824,
wRref¼0.2384, and wRgt¼0.2254. All calculations and struc-
ture solution was accomplished by using SHELXTL-PC
VERSION of software. Crystallographic data for the struc-
ture have been deposited with Cambridge Crystallographic
Database as supplementary publication number CCDC
(295846).
ꢀ
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Tetrahedron 2005, 61, 9990–9995.
ꢀ
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8. Sone, T.; Ohba, Y.; Moriya, K.; Kumada, H.; Ito, K.
Tetrahedron 1997, 53, 10689–10698.
Acknowledgements
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Authors acknowledge with gratitude the financial assistance
received from the Department of Science and Technology
(Govt. of India), UGC and CSIR for junior research fellow-
ships to two of them (A.C. and S.P.S.). DST (FIST) grant for
CCD X-ray diffractometer at the Department of Chemistry,
I.I.T., New Delhi had been invaluable for this work. Sophis-
ticated Analytical Instrument Facility, Central Drug
Research Institute, Lucknow is thanked for recording the
FAB Mass spectra reported in this paper.
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