A novel calix[4]arene-based neutral semicarbazone receptor for anion recognition

Article abstract of DOI:10.1016/j.tetlet.2007.06.075

A series of novel calix[4]arene-based neutral semicarbazone and thiosemicarbazone receptors have been synthesized and characterized. The molecular receptor 4a recognizes HSO₄^- in preference to other anions (Cl^-, Br^-

Full text of DOI:10.1016/j.tetlet.2007.06.075

Tetrahedron Letters 48 (2007) 6054–6058
A novel calix[4]arene-based neutral semicarbazone receptor
for anion recognition
Har Mohindra Chawla,* Satya Narayan Sahu and Rahul Shrivastava
Department of Chemistry, Indian Institute of Technology, Hauz Khas, New Delhi 110 016, India
Received 30 April 2007; revised 2 June 2007; accepted 14 June 2007
Available online 20 June 2007
Abstract—A series of novel calix[4]arene-based neutral semicarbazone and thiosemicarbazone receptors have been synthesized and
characterized. The molecular receptor 4a recognizes HSO4 in preference to other anions (Clꢀ, Brꢀ, Iꢀ, ClO4ꢀ, H2PO and PF6
)
ꢀ
ꢀ
ꢀ
4
through a 1:1 binding-stoichiometry.
ꢀ 2007 Elsevier Ltd. All rights reserved.
ꢀ
Anion recognition is extremely important for resolving
biological, chemical and environmental issues.1,2
Though a large volume of research data is available on
recognition of cations, very few molecular receptors
have been examined for anions.3 Different strategies
adopted for anion recognition essentially consist of
either acquiring the positively charged molecular hosts,
which interact with anions through electrostatic interac-
tions4,5 or by utilizing the neutral molecular hosts, which
recognize anions through donor–acceptor attributes,
hydrophobic effects and hydrogen bonds.6 The direc-
tional nature of hydrogen bonds has recently been
explored for better selectivity in recognition processes.6
It was envisaged that the phenolic oligomers represented
by calix[n]arenes could in principle provide excellent
platforms for construction of attractive recognition sites
for host–guest interactions7 and it should be possible to
design molecular receptors for anion recognition by
employing activated amides, urea and thiourea function-
alities.8,9 To the best of our knowledge, the utilization of
calixarenes bearing semicarbazone and thiosemicarba-
zone subunits at their lower rim have not been examined
for anion recognition despite the availability of facile
synthetic protocols. We report herein, the synthesis,
characterization and anion binding properties of a novel
calix[4]arene receptors bearing two semicarbazone and
thiosemicarbazone moieties at the distal 1,3-positions.
These receptors were found to demonstrate significant
binding ability for tetrahedral HSO4 ions in preferencꢀe
to otherꢀanions including Clꢀ, Brꢀ, Iꢀ, ClO4ꢀ, H2PO
4
and PF6
.
The required starting material, calix[4]arene 1 was
obtained by using a literature procedure.10a Dibromo-
alkylation of 1 was achieved by refluxing with 1,3-
dibromopropane in the presence of K2CO3 in CH3CN
for 48–96 h to give 2 in 87% yield.10b Compounds 3a
and 3b were obtained in 86% and 83% yields, respec-
tively, when bis(bromopropyl)-calix[4]arene
2 was
refluxed with p-hydroxybenzaldehyde or p-hydroxy-
acetophenone in the presence of K2CO3 in anhydrous
acetonitrile under a nitrogen atmosphere.11 Treatment
of 3a and 3b with semicarbazide or thiosemicarbazide
reagents12 gave 4a–d13 in good yields as illustrated in
Scheme 1.
Compounds 4a–d were characterized by analysis of their
1H NMR, 13C NMR, FAB-MS and FT-IR spectra. For
1
example, the H NMR spectrum of 4a showed a typical
AB pattern represented by two pairs of doublets at d
3.29 and d 4.14 for the axial and equatorial protons,
respectively, which indicated that 4a existed in a sym-
metrical cone conformation. This was further confirmed
by the observation of a distinct signal at d 31.2 for
13
the methylene carbon in the C NMR spectrum.13
The azo-methine proton (HC@N) appeared as a non-
exchangeable singlet at d 7.59 while the –NH2, –OH
and –NH protons appeared at d 5.77, 8.12 and 10.09,
respectively. These signals disappeared on deuteration
with D2O. Individual assignment of the –OH, –NH
and –NH2 protons were further confirmed by
Keywords: Calix[4]arene; Semicarbazone; Thiosemicarbazone.
*
Corresponding author. Tel.: +91 11 26591517; fax: +91 11
26591502; e-mail: hmchawla@chemistry.iitd.ernet.in
0040-4039/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.06.075

H. M. Chawla et al. / Tetrahedron Letters 48 (2007) 6054–6058
6055
( i )
O
O
(H2C)3
Br
O
O
O
O
O
O
H
H
H
H
H
(CH2)3
Br
H
1
2
( ii )
O
O
O
(H2C)3
O
O
O
(H2C)3
O
O
O
O
(CH2)3
O
H
H
H
H
(CH2)3
( iii )
O
X
C
C
X
X
C
N
C
N
X
O
O
N
N
H
H
3a X =
H
C
Y
Y
C
3b X = CH3
H2N
NH2
No.
4a
4b
4c
X
H
CH3
H
CH 3
Y
Yield(%)
O
O
S
88
78
82
79
4d
S
Scheme 1. Reagents and conditions: (i) Br–(CH2)3–Br, K2CO3,
CH3CN, reflux; (ii) p-hydroxybenzaldehyde or p-hydroxyacetophe-
none, K2CO3, CH3CN, reflux; (iii) NH2–NH–C(Y)–NH2, methanol,
50 ꢁC, reflux.
Figure 1. Partial 1H NMR (300 MHz and 298 K) spectra of host 4a
(10 mM) upon addition of various aliquots of TBAÆHSO4 (40 mM) in
ꢀ
CDCl3. (A) Host 4a; (B) 4a + 0.5 equiv of HSO4 (C) 4a + 0.75 equiꢀv
ꢀ
ꢀ
of HSO4 (D) 4a + 1.0 equiv of HSO4 (E) 4a + 1.5 equiꢀv of HSO4
ꢀ
(F) 4a + 2.0 equiv of HSO4 (G) 4a + 2.5 equiv of HSO4
= CH, | = OH).
(
= NH,
comparison with those of their precursor compounds,
NOESY experiments and quantitative integrals. The
FT-IR spectrum exhibited a sharp peak at 1605 cmꢀ1
for the >C@N– absorptions.
160
2
The synthesized compounds 4a–d were examined for
their interaction with ꢀvarious anions (Clꢀ, Brꢀ, Iꢀ,
ClO4ꢀ, HSO4ꢀ, H2PO4 and PF6ꢀ) in the form of their
tetrabutylammonium salts. The recognition characteris-
tics of 4a were investigated in detail by 1H NMR experi-
ments in deuterated chloroform, which revealed a
significant downfield shift for the NH and CH proton
resonances on addition of tetrabutylammonium hydro-
gen sulfate while no change in the chemical shifts
140
O
OH
(CH2)3
120
100
80
O
H
H
C
N
60
N
C
NH proton
40
O
20
CH proton
H2N
0
0
0.01
0.02
0.03
occurred when Clꢀ, Brꢀ, Iꢀ, ClO4ꢀ, H2PO and PF6
ꢀ
ꢀ
Concentration of anion
4
Figure 2. 1H NMR titration curve of 4a with TBAÆHSO4 (CDCl3,
300 MHz and 298 K).
were added under the same experimental conditions
(Table 1). Similar downfield shifts for the NH and CH
proton resonances were also observed for receptor 4c
on addition of tetrabutylammonium hydrogen sulfate
in d6-acetone (4c had poor solubility in CDCl3).
the CH signal at d 7.59 for receptor 4a were markedly
affected by addition of tetrabutylammonium hydrogen
sulfate while no effect on the chemical shift was observed
for the phenolic OH signal at d 8.12. Figure 1 illustrates
that maximum downfield shifts were observed for the
NH and CH protons of 4a upon addition of 1.0 equiv
of TBAÆHSO4. Various aliquots of a 40 mM solution
of tetrabutylammonium hydrogen sulfate were added
to a 10 mM solution of 4a and the chemical shifts of
the NH proton were recorded at each concentration un-
til the saturation point was observed (Fig. 2). Analysis
of saturation data with a nonlinear regression curve-fit-
ting programme WinEQNMR,15 revealed a 1:1 complex
The 1H NMR titration experiments conducted in
14
CDCl3 indicated that the NH signal at d 10.09 and
Table 1. Chemical shift values (Dd, ppm) of the NH, CH and OH
proton resonances of 4a upon addition of 100 equiv of anions (as
tetrabutylammonium salts) in CDCl3 (300 MHz and 298 K)
Anion
NH
CH
OH
Cl
Br
I
ClO4
HSO4
H2PO4
PF6
nsa
ns
ns
ns
0.47
ns
ns
ns
ns
ns
ns
0.21
ns
ns
ns
ns
ns
ns
ns
ns
ns
formation with a binding constant of 4.5 · 103 Mꢀ1
.
A Job plot experiment further confirmed the 1:1
binding-stoichiometry with maximum complexation at
0.5 mol fraction of anion as shown in Figure 3.
a ns indicates no change in chemical shift.

6056
H. M. Chawla et al. / Tetrahedron Letters 48 (2007) 6054–6058
HSO4 in preference to Clꢀ, Brꢀ, Iꢀ, ClO4ꢀ, H2PO
ꢀ
ꢀ
0.25
0.2
0.15
0.1
0.05
0
4
ꢀ
and PF6 ions. The enhanced selectivity of 4a for
ꢀ
HSO4 could be due to strong hydrogen bond interac-
tions between the receptor NH and CH protons through
1:1 binding-stoichiometry. Further investigations to
understand the exact nature of the binding of HSO4
ꢀ
with 4a are in progress.
Acknowledgements
The authors are grateful to the Sophisticated Analytical
Instrument Facility, CDRI, Lucknow for FAB-MS
spectra, the Department of Science and Technology,
Government of India, for financial assistance and the
Council of Scientific and Industrial Research, India for
senior research fellowships to S.N.S. and R.S.
0
0.2
0.4
0.6
0.8
1
mol fraction of anion
Figure 3. Job plot of the titration of 0.01 M TBAÆHSO4 with 10ꢀ2 M
receptor 4a in CDCl3.
References and notes
The enhanced selectivity of calix[4]arene semicarbazone
receptor 4a towards HSO4 ions could be attributed to
ꢀ
1. (a) Krik, K. L. Biochemistry of Halogens and Inorganic
Halides; Plenum Press: New York, 1991; p 591; (b) de
Silva Frausto, J. J. R.; Williams, R. J. P. Struct. Bond.
(Berlin) 1976, 29, 67.
the influence of hydrogen bonding. Preliminary observa-
tions of the chemical shift for the NH and CH proton
ꢀ
resonances upon addition of HSO4 to a CDCl3 solu-
tion of 4a indicated that both the NH and CH protons
participate in the formation of co-operative hydrogen
bonds with the anionic oxygens while the phenolic pro-
tons of the calix[4]arene skeleton do not. Hence the
chemical shift of the OH signal remained unaffected dur-
ing the titration (Fig. 1).
2. (a) Beer, P. D.; Hopkins, P. K.; McKinney, J. D. Chem.
Commun. 1999, 1253–1254; (b) Ullman’s Encyclopedia of
Industrial Chemistry, 6th ed.; Wiley-VCH: New York,
Germany, 1998.
3. (a) Schmidtchen, F. P.; Berger, M. Chem. Rev. 1997, 97,
1609–1646; (b) Beer, P. D.; Gale, P. A. Angew. Chem., Int.
Ed. 2001, 40, 486–516; (c) Snowden, T. S.; Anslyn, V.
Curr. Opin. Chem. Biol. 1999, 3, 740–746.
In the cases of 4b and 4d (X = CH3, Y = O, S), no sig-
nificant shift in the NH proton resonance was observed
thereby indicating that the azo-methine proton (HC@N)
is important for the specificity and anion binding. This is
probably due to appropriate distances between the NH
and CH protons, which provide a proper binding site
4. Llinares, J. M.; Powell, D.; Bowman-James, K. Coord.
Chem. Rev. 2003, 240, 57–75.
5. Best, M. D.; Tobey, S. L.; Anslyn, E. V. Coord. Chem.
Rev. 2003, 240, 3–15.
6. (a) Antonisse, M. M. G.; Reinhoudt, D. N. Chem.
Commun. 1998, 443–448; (b) Sessler, J. L.; Camiolo, S.;
Gale, P. A. Coord. Chem. Rev. 2003, 240, 17–55; (c)
Boiocchi, M.; Del Boca, L.; Gomez, D. E.; Fabbrizzi, L.;
Licchelli, M.; Monzani, E. J. Am. Chem. Soc. 2004, 126,
16507–16514; (d) Gunnlaugsson, T.; Kruger, P. E.; Jensen,
P.; Tierney, J.; Ali, H. D. P.; Hussey, G. M. J. Org. Chem.
2005, 70, 10875–10878.
ꢀ
in 4a for entrapment of HSO4 ions such that the three
ꢀ
oxygen atoms of the tetrahedral HSO4 ion form hydro-
gen bonds with the NH and CH protons of the semicar-
ꢀ
bazone subunit. A possible model for the 4a–HSO4
complex is shown in Scheme 2, which is being explored
further.
7. (a) Gutsche, C. D. In Calixarenes: Monographs in Supra-
molecular Chemistry; Stoddart, J. F., Ed.; The Royal
Society of Chemistry: Cambridge, UK, 1989; (b) Gutsche,
C. D. In Calixarenes Revisited: Monographs in Supramo-
lecular Chemistry; Stoddart, J. F., Ed.; The Royal Society
of Chemistry: Cambridge, UK, 1998; (c) Chawla, H. M.;
Pant, N.; Srivastava, B.; Upreti, S. Org. Lett. 2006, 8,
2237–2240; (d) Chawla, H. M.; Singh, S. P.; Sahu, S. N.;
Upreti, S. Tetrahedron 2006, 62, 7854–7865; (e) Chakra-
barti, A.; Chawla, H. M.; Francis, T.; Pant, N.; Upreti, S.
Tetrahedron 2006, 62, 1150–1157; (f) Chawla, H. M.;
Singh, S. P.; Upreti, S. Tetrahedron 2006, 62, 2901–2911;
(g) Chawla, H. M.; Pant, N.; Srivastava, B. Tetrahedron
Lett. 2005, 46, 7259–7262; (h) Chawla, H. M.; Srinivas, K.
J. Chem. Soc., Chem. Commun. 1994, 2593–2594; (i)
Chawla, H. M.; Srinivas, K. J. Org. Chem. 1996, 61, 8464–
8467.
In conclusion, we have synthesized a series of novel
calix[4]arene-based neutral semicarbazone and thiosemi-
carbazone receptors 4a–d, which selectively recognize
O
O
O
O
O
O
O
O
H
(H2C)3
O
H
H
(H2C)3
O
H
(CH2)3
O
(CH2)3
O
-
HSO
+
-
4
-
HSO4
-
O
H
C
C
H
H
C
C
H
H
N
N
N
N
S
8. (a) Bondy, C. R.; Loeb, S. J. Coord. Chem. Rev. 2003, 240,
77–99; (b) Tumcharern, G.; Tuntulani, T.; Coles, S. G.;
Hursthouse, M. B.; Kilburn, J. D. Org. Lett. 2003, 5,
4971–4974; (c) Morzherin, Y.; Rudkevich, D. M.; Ver-
boom, W.; Reinhoudt, D. N. J. Org. Chem. 1993, 58,
N
O
O
H
N
H
N
N
H
C
O
O
C
OH
C
O
O
C
H2N
NH2
H2N
NH2
ꢀ
Scheme 2. Possible binding model of 4a with HSO4
.

H. M. Chawla et al. / Tetrahedron Letters 48 (2007) 6054–6058
6057
7602–7605; (d) Beer, P. D.; Gale, P. A.; Hesek, D.
Tetrahedron Lett. 1995, 36, 767–770; (e) Cameron, B. R.;
Loeb, S. J. Chem. Commun. 1997, 573–574; (f) Wu, J. L.;
He, Y. B.; Zeng, Z. Y.; Wei, L. H.; Meng, L. Z.; Yang, T.
X. Tetrahedron 2004, 60, 4309–4314.
white solids. Selected analytical data for compounds 4a–d
are given below: Compound 4a: yield (88%); mp =
267 5 ꢁC. IR (KBr): 3336 (OH); 1689 (C@O); 1605
(C@N). Anal. Calcd for C50H50N6O8: C, 69.59; H, 5.84;
N, 9.74. Found: C, 69.30; H, 5.92; N, 9.59. FAB-MS m/z
Calcd: 862. Found 863 (M+H+). 1H NMR (300 MHz,
CDCl3): d 2.30–2.34 (m, 4H, –CH2–CH2–CH2–), d 3.29 (d,
4H, J = 12.8 Hz, Ar–CH2–Ar), d 3.92 (t, 4H, J = 5.4 Hz,
–OCH2), d 4.14 (d, 4H, J = 12.8 Hz, Ar–CH2–Ar), d 4.23
(t, 4H, J = 5.6 Hz, –CH2O), d 5.77 (br s, 4H, D2O
exchange –NH2), d 6.56 (t, 2H, J = 7.2 Hz, Ar-H), d 6.66
(t, 2H, J = 7.3 Hz, Ar-H), d 6.74 (d, 4H, J = 8.3 Hz, Ar-
Hbenzaldehyde), d 6.84 (d, 4H, J = 7.4 Hz, Ar-H), d 6.96 (d,
9. (a) Wu, F. Y.; Li, Z.; Wen, Z. C.; Zhou, N.; Zhao, Y. F.;
Jiang, Y. B. Org. Lett. 2002, 4, 3203–3205; (b) Cho, E. J.;
Moon, J. W.; Ko, S. W.; Lee, J. Y.; Kim, S. K.; Yoon, J.;
Nam, K. C. J. Am. Chem. Soc. 2003, 125, 12376–12377; (c)
Kim, K. S.; Yoon, J. Chem. Commun. 2002, 770–771; (d)
Dudic, M.; Lhotak, P.; Stibor, I.; Lang, K.; Proskova, P.
Org. Lett. 2003, 5, 149–152.
10. (a) Iqbal, M.; Mangiafico, T.; Gutsche, C. D. Tetrahedron
1987, 43, 4917–4930; (b) Li, Z. T.; Ji, G. H.; Zhao, C. X.;
Yuan, S. D.; Ding, H.; Huang, C.; Du, A. L.; Wei, M. J.
Org. Chem. 1999, 64, 3572–3584.
4H, J = 7.3 Hz, Ar-H),
d 7.37 (d, 4H, J = 8.3 Hz,
Ar-Hbenzaldehyde), d 7.59 (s, 2H, –CHN), d 8.12 (s, 2H,
D2O exchange –OH), d 10.09 ( s, 2H, D2O exchange
–NH). 13C NMR (CDCl3): d 29.7, 31.2, 64.8, 72.5, 114.7,
119.2, 125.7, 128.7, 128.5, 129, 131.9, 133.1, 151.2, 152.9,
163.7, 190.7.
Compound 4b: yield (78%); mp = 263 4 ꢁC. IR (KBr):
3408 (OH); 1702 (C@O); 1602 (C@N). Anal. Calcd for
C52H54N6O8: C, 70.09; H, 6.11; N, 9.43. Found: C, 69.98;
H, 6.01; N, 9.59. FAB-MS m/z Calcd: 890. Found 891
(M+H+). 1H NMR (300 MHz, CDCl3): d 2.02 (s, 6H,
–CCH3), d 2.32–2.36 (m, 4H,–CH2–CH2–CH2–), d 3.30 (d,
4H, J= 12.1 Hz, Ar–CH2–Ar), d 3.92 (br s, 4H, –OCH2), d
4.18 (d, 4H, J = 12.1 Hz, Ar–CH2–Ar), d 4.29 (br s, 4H,
–CH2O), d 6.32 (br s, 4H, D2O exchange –NH2), d
6.84–6.89 (m, 12H, Ar-H), d 6.97 (d, 4H, J = 8.3 Hz,
11. General procedure for the synthesis of compounds 3a,b:
A
mixture of 2 (1.17 mmol), potassium carbonate
(7.19 mmol) and p-hydroxybenzaldehyde (or p-hydroxy-
acetophenone) (4.5 mmol) was stirred under reflux in
20 mL of anhydrous acetonitrile for 48 h. The reaction
mixture was cooled to room temperature and then
carefully neutralized with dilute hydrochloric acid and
extracted with chloroform. The organic layer was washed
with water, dried over Na2SO4 and evaporated to dryness.
The white solid residue was purified by column chroma-
tography on silica gel using hexane/ethyl acetate (gradient
from 9.5:0.5 to 8:2) as eluent. Selected analytical data for
compounds 3a,b are given below: Compound 3a: yield
(86%); mp >240 ꢁC. IR (KBr): 3360 (OH); 1689 (C@O).
Anal. Calcd for C48H44O8: C, 76.99; H, 5.92. Found: C,
76.69; H, 5.76. FAB-MS m/z Calcd: 748. Found 748
(M+). 1H NMR (300 MHz, CDCl3): d 2.36 (q, 4H,
Ar-Hacetophenone),
d
7.47 (d, 4H, J = 8.3 Hz,
Ar-Hacetophenone), d 8.27 (s, 2H, D2O exchange –OH), d
8.45 (s, 2H, D2O exchange –NH). 13C NMR (CDCl3): d
26.4, 29.7, 31.2, 64.8, 72.5, 114.7, 119.2, 125.7, 128.7,
128.5, 129.0, 131.9, 133.1, 151.2, 152.9, 163.7, 195.7.
Compound 4c: yield (82%); mp = 261 5 ꢁC. IR (KBr):
3304 (OH); 1089 (C@S); 1604 (C@N). Anal. Calcd for
C50H50N6O6S2: C, 67.09; H, 5.63; N, 9.39. Found: C,
67.18; H, 5.82; N, 9.14. FAB-MS m/z Calcd: 894. Found
J = 5.9 Hz, –CH2–CH2–CH2–),
d
3.36 (d, 4H,
J = 12.9 Hz, Ar–CH2–Ar), d 4.12 (t, 4H, J = 5.5 Hz,
–OCH2), d 4.20 (d, 4H, J = 12.9 Hz, Ar–CH2–Ar), d
4.48 (t, 4H, J = 6.2 Hz, –CH2O), d 6.64 (t, 2H, J = 7.3 Hz,
Ar-H), d 6.72 (t, 2H, J = 7.6 Hz, Ar-H), d 6.90 (d, 4H,
J = 7.4 Hz, Ar-Hbenzaldehyde), d 7.03 (d, 4H, J = 7.2 Hz,
Ar-H), d 7.06 (d, 4H, J = 7.1 Hz, Ar-H), d 7.79 (d, 4H,
J = 7.4 Hz, Ar-Hbenzaldehyde), d 8.01 (s, 2H, D2O exchange
–OH), d 9.83 (s, 2H, CHO). 13C NMR (CDCl3): d 29.7,
31.3, 64.8, 72.5, 114.8, 119.7, 125.7, 127.8, 128.6, 129.6,
131.9, 133.1, 151.2, 152.9, 191.8.
1
895 (M+H+). H NMR (300 MHz, (CD3)2CO): d 2.45 (q,
4H, J = 5.6 Hz, –CH2–CH2–CH2–),
d 3.44 (d, 4H,
J = 12.8 Hz, Ar–CH2–Ar), d 4.23 (t, 4H, J = 4.2 Hz,
–OCH2), d 4.30 (d, 4H, J = 12.8 Hz, Ar–CH2–Ar), d
4.56 (t, 4H, J = 4.1 Hz, –CH2O), d 6.58 (t, 2H, J = 7.3 Hz,
Ar-H), d 6.69 (t, 2H, J = 7.4 Hz, Ar-H), d 7.00 (d, 4H,
Compound 3b: yield (83%); mp >245 ꢁC. IR (KBr): 3336
(OH); 1675 (C@O). Anal. Calcd for C50H48O8: C, 77.30;
H, 6.23. Found: C, 77.18; H, 5.86. FAB-MS m/z Calcd:
776. Found 777 (M+H+). 1H NMR (300 MHz, CDCl3): d
2.28–2.32 (m, 4H, –CH2–CH2–CH2–), d 2.41 (s, 6H,
–COCH3), d 3.28 (d, 4H, J = 12.9 Hz, Ar–CH2–Ar), d 4.04
(t, 4H, J = 5.1 Hz, –OCH2), d 4.14 (d, 4H, J = 12.9 Hz,
Ar–CH2–Ar), d 4.38 (t, 4H, J = 6.2 Hz, –CH2O), d 6.55 (t,
2H, J = 7.4 Hz, Ar-H), d 6.63 (t, 2H, J = 7.6 Hz, Ar-H), d
6.81 (d, 4H, J = 7.4 Hz, Ar-H), d 6.89 (d, 4H, J = 8.4 Hz,
Ar-Hacetophenone), d 6.95 (d, 4H, J = 7.5 Hz, Ar-H), d 7.80
(d, 4H, J = 8.4 Hz, Ar-Hacetophenone), d 7.96 (s, 2H, D2O
exchange –OH). 13C NMR (CDCl3): d 26.2, 29.7, 31.2,
64.7, 72.6, 114.1, 115, 119.2, 125.6, 127.8, 128.4, 129.0,
130.3, 130.5, 133.1, 151.2, 153.0, 162.7, 196.8.
J = 7.5 Hz, Ar-H),
d
7.07 (d, 4H, J = 8.3 Hz,
Ar-Hbenzaldehyde), d 7.12 (d, 4H, J = 7.4 Hz, Ar-H), d
7.40 (br s, 4H, D2O exchange –NH2), d 7.73 (d, 4H,
J = 8.3 Hz, Ar-Hbenzaldehyde), d 8.09 (s, 2H, –CHN), d 8.38
(s, 2H, D2O exchange –OH), d 10.34 (s, 2H, D2O exchange
–NH). 13C NMR ((CD3)2CO): d 29.7, 30.9, 64.7, 72.9,
114.9, 119.2, 125.3, 127.9, 128.6, 129.0, 129.2, 142.6, 146.2,
150.2, 205.4.
Compound 4d: yield (79%); mp = 266 5 ꢁC. IR (KBr):
3336 (OH); 1091 (C@S); 1587 (C@N). Anal. Calcd for
C52H54N6O6S2: C, 67.65; H, 5.90; N, 9.10. Found: C,
67.48; H, 5.85; N, 9.31. FAB-MS m/z Calcd: 922. Found
1
923 (M+H+). H NMR (300 MHz, (CD3)2CO): d 2.21 (s,
6H, –CCH3), d 2.42–2.46 (m, 4H, J = 5.4 Hz, –CH2–CH2–
CH2–), d 3.42 (d, 4H, J = 12.7 Hz, Ar–CH2–Ar), d 4.21 (t,
4H, J = 4.0 Hz, –OCH2), d 4.33 (d, 4H, J = 12.7 Hz, Ar–
CH2–Ar), d 4.58 (t, 4H, J = 4.2 Hz, –CH2O), d 6.56 (t, 2H,
J = 7.4 Hz, Ar–H), d 6.63 (t, 2H, J = 7.5 Hz, Ar-H), d 7.12
(d, 4H, J = 7.5 Hz, Ar-H), d 7.17 (d, 4H, J = 8.3 Hz,
Ar-Hacetophenone), d 7.22 (d, 4H, J = 7.4 Hz, Ar-H), d 7.42
(br s, 4H, D2O exchange –NH2), d 7.78 (d, 4H, J = 8.3 Hz,
Ar-Hacetophenone), d 8.36 (s, 2H, D2O exchange –OH), d
10.32 (s, 2H, D2O exchange –NH). 13C NMR ((CD3)2CO):
d 27.2, 29.4, 30.4, 65.7, 73.6, 114.4, 117.6, 125.7, 126.9,
128.7, 129.3, 129.8, 145.2, 149.2, 200.4.
12. Zengin, G.; Huffman, J. W. Turk. J. Chem. 2006, 30, 139–
144.
13. General procedure for the synthesis of compounds 4a–d: A
solution of 3a–b (1.3 mmol) in 20 mL of methanol was
treated with 17.0 mL of semicarbazide/thiosemicarbazide
solution.12 The mixture was refluxed on a water bath
(50 ꢁC) until crystallization began. Further crystallization
was allowed to continue at room temperature and the
product obtained was filtered and dried under vacuum to
give calix[4]arene-bis(semicarbazone) derivatives 4a–d as

6058
H. M. Chawla et al. / Tetrahedron Letters 48 (2007) 6054–6058
14. 1H NMR titration: A 10 mM solution of the host 4a was
prepared in CDCl3. To 0.5 mL of 4a solution, 0–5 equiv of
tetrabutylammonium hydrogen sulfate (40 mM) were
added to an NMR tube and the spectra were recorded.
The chemical shifts of the NH and CH protons were
followed and plotted against the equivalents of TBAÆHSO4
added. Job plot: Stock solutions of the host 4a (10 mM)
and tetrabutylammonium hydrogen sulfate (10 mM) were
prepared in CDCl3. A total volume of 500 lL of 4a and
TBAÆHSO4 were added to nine NMR tubes in the
following volume ratios: 50:450, 100:400, 150:350,
200:300, 250:250, 200:300, 150:350, 100:400, 50:450.
15. Hynes, M. J. Chem. Soc., Dalton Trans. 1993, 311–
312.