Calix[4]arene based neutral receptor for dihydrogen phosphate anion

Article abstract of DOI:10.1016/j.tet.2007.11.010

A series of novel calix[4]arene hydrazone and semicarbazone based neutral receptors have been synthesized and characterized by IR, UV-vis, and NMR spectroscopies. The preliminary UV-vis and ¹H NMR titration experiments revealed that 25,26,27,28

Full text of DOI:10.1016/j.tet.2007.11.010

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 741e748
www.elsevier.com/locate/tet
Calix[4]arene based neutral receptor for dihydrogen phosphate anion
*
Har Mohindra Chawla , Suneel Pratap Singh
Department of Chemistry, Indian Institute of Technology, Hauz Khas, New Delhi-110016, India
Received 21 June 2007; received in revised form 16 October 2007; accepted 1 November 2007
Available online 6 November 2007
Abstract
A series of novel calix[4]arene hydrazone and semicarbazone based neutral receptors have been synthesized and characterized by IR, UVe
1
vis, and NMR spectroscopies. The preliminary UVevis and H NMR titration experiments revealed that 25,26,27,28-tetrapropoxycalix[4]arene
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
tetra-semicarbazone can recognize H
ꢀ
2
PO
4
through a 1:1 binding-stoichiometry in preference over other anions (Cl , Br , I , HSO
4
, ClO , and
4
CH COO ).
Ó 2007 Published by Elsevier Ltd.
3
Keywords: Calix[4]arene; Dihydrogen phosphate anion; Recognition; Neutral receptor; Semicarbazone
1
. Introduction
For instance, prokaryotic, periplasmic phosphate and sulfate
5
binding proteins exhibit selectivities of more than 10 for bind-
The design and synthesis of neutral electron deficient abi-
otic receptors for anions of biochemical, medical, and environ-
1
mental importance is an area of intense research activity. As
ing phosphate over sulfate and of sulfate over phosphate, respec-
8
d
tively. In both of these proteins the specific binding
exclusively takes place through hydrogen bonding.
a consequence of their unique upper and lower rim topology,
calixarenes are attractive molecular platforms for ion recogni-
The availability of synthetic receptors for dihydrogen phos-
phate can lead to a better understanding of the processes in-
volved in selective biological mimics. Recent reports on
synthetic receptors containing urea, uranyl containing salenes,
and sulphonamides derived from tris(aminoethyl)-amine
2
3
tion. Though generally examined for cation recognition, the
development of calixarene derivatives for recognition of an-
ions is comparatively nascent, in part due to higher free energy
of solvation of anions and their dependence on slight varia-
ꢀ
9
(TREN) for H PO support this view. In this paper, we report
2
4
4
tions in pH.
our results on calixarene based molecular receptors for recog-
ꢀ
Some of the organic synthetic receptors examined for anions
either have positively charged units (e.g., ammonium or guani-
dium units) or contain a metal center, which can directly coordi-
nition of H PO anions.
2
4
2. Result and discussion
5
nate to the anion of interest. Anion binding in charged receptors
is achieved by electrostatic interactions (as in the case of poly-
2.1. Design and synthesis of calix[4]arene based
6
ammonium receptors for binding ATP). It was envisaged that
receptors
in principle, anion receptors can also be possible by neutral mo-
lecular receptors that possess electron deficient or Lewis acid
The required starting materials, p-tert-butyl-calix[4]arene 1
and debutylated calix[4]arene, were obtained by following
7
sites in their constitution to form hydrogen bond interactions.
8c
8
a,b
Crystal structures of sulfate and phosphate binding pro-
teins provide useful insights into their binding characteristics.
10a,b
the procedures available in the literature.
The 25,27-dime-
thoxy-calix[4]arene, 25,27-di(ethoxycarbonylmethoxy)-calix[4]-
arene, and p-tert-butyl-25,27-di(ethoxycarbonylmethoxy)-
calix[4]arene were obtained by refluxing calix[4]arene with
respective alkyl halides with K CO in CH CN for 48 h as
*
Corresponding author. Tel.: þ91 11 26591517; fax: þ91 11 26591502.
E-mail address: hmchawla@chemistry.iitd.ernet.in (H.M. Chawla).
2
3
3
0040-4020/$ - see front matter Ó 2007 Published by Elsevier Ltd.
doi:10.1016/j.tet.2007.11.010

742
H.M. Chawla, S.P. Singh / Tetrahedron 64 (2008) 741e748
1
0cef
described previously.
ix[4]arene was synthesized by alkylation with propyl bromide
25,26,27,28-(Tetrapropoxy)-cal-
formyl groups. The synthesized iminamides showed character-
ꢀ
1
istic absorptions for e(C]O)eNe (1670e1705 cm ) and
1
0g,h
ꢀ1
in the presence of NaH in DMF for 48 h.
calix[4]arene ethers and esters were formylated by using hexa-
methylenetetramine (HMTA)/trifluoroaceticacid (TFA) system
to yield compounds 2, 3, 6, and 8, which were further re-
acted with semicarbazide$hydrochloride, phenyl hydrazine,
and its nitro derivatives to yield target compounds (4, 5, 7,
and 9e11) in good yields (>80%, Scheme 1).
The synthesized
eNeH (3310e3460 cm ) groups. Compounds 5 and 9e11
also showed characteristic absorptions for an ester functional-
ꢀ
1
ity at w1750 cm (Table 1). The resonance signals for the
methylene bridge carbon in the C NMR spectra of 4, 5, 7,
and 9e11 suggested that they were present in their cone con-
1
1
13
1
formation. The exact substitution pattern and conformation
2
1
of these products were further confirmed by H NMR spec-
troscopy. For instance, 7 exhibited signals at d 9.93 (s), 7.57
(s), 7.23 (s), and 6.47 (s) for NH, CH, ArH, and NH , respec-
2
2
.2. Characterization of the synthesized compounds
tively, while methylene bridge and propyl protons could be
observed at d 4.37 (d), 3.30 (d) and 3.83 (br s), 1.95 (br q),
1
0.99 (br s) in the H NMR spectrum indicating its tetrasubsti-
tuted symmetric cone conformation.
The identification of the compounds (4, 5, 7, and 9e11) by
1
13
IR, H and C NMR, FAB mass spectra, and elemental anal-
ysis revealed that the reaction exclusively takes place at the
NH2
HN
2
H N
O
O
OHC CHO
HO OH
NH
H
H
N
3
steps
N
(i)-(iii)
(iv)
O
O
OH HO OH
1
HO
R
R
R
O
HO OH
O
2
-CH3
3
steps
R
R
3
-CH2CO(O)CH2CH3
(v)-(vii)
2
steps
R
(ix)-(x)
4
5
-CH3
-CH2CO(O)CH3
H2N
NH2
O O
OHC
CHO
H2N
O
NH2
O
OHC CHO
CHO
OHC
HN
NH
NH
N
HN
N
N N
O O
7
H
H
(
viii)
H
H
O
HO OH
O
O
O O
O
O
O
O
O
O
O
O
8
6
(xii)
(
xi)
R2
R1
R2
R1
NH2
HN
2
H N
O
NH
NH
N
HN
H
H
N
H
N
H
N
R1
R2
1
0
H
H
H
NO2
11
O
HO OH
O
HO OH
O
O
O
O
O
O
O
O
O
O
9
Scheme 1. Synthesis of 4 and 5: (i) AlCl
3
, phenol, toluene, rt, stirring, 1 h (yield¼75%); (ii) BrCH
2
CO(O)CH
eNH
, phenol, toluene, rt, stirring, 1 h (yield¼75%); (vi) BrCH
eNH eC(O)eNH
$HCl, toluene/methanol, reflux, 24 h (yield for 7¼87%). Synthesis of
CN, reflux, 48 h (yield¼64%); (x) TFA, HMTA, reflux, 24 h (yield for 8¼82%); (xi) NH eNH eC(O)eNH $HCl,
toluene/methanol, reflux, 24 h (yield for 9¼86%); (xii) NH eNH ePheR (R¼H or NO ), toluene/methanol, reflux, 24 h (yields for 10¼85%, for 11¼81%).
2
CH
eC(O)eNH
CH CH
3
or MeI, K
$HCl, toluene/methanol, reflux,
, NaH, DMF, rt, stirring, 36 h
2 3 3
CO , CH CN, reflux, 48 h
(
yields¼62% and 60%, respectively); (iii) TFA, HMTA, reflux, 1 h (yields for 2¼64%, for 3¼85%); (iv) NH
2
2
2
2
4 h (yields for 4¼82%, for 5¼84%). Synthesis of 7: (v) AlCl
3
2
2
3
(
yield¼57%); (vii) TFA, HMTA, reflux, 48 h (yield¼65%); (viii) NH
2
2
2
9
e11: (ix) BrCH CO(O)CH CH , K CO , CH
2
2
3
2
3
3
2
2
2
2
2
2

H.M. Chawla, S.P. Singh / Tetrahedron 64 (2008) 741e748
743
Table 1
Important IR and NMR signals of synthesized compounds
ꢀ1
1
Characteristic H NMR signals (d, 25 C, 300 MHz)
ꢁ
13
C NMR signals
for ArCH Ar
Compd. no. IR nmax/cm
2
NH
OH
CH
ArHcalixarene core
NH
2
2
ArCH Ar
ꢁ
(
d, 25 C, 75 MHz)
4
5
3342, 1677
10.12 (s)
8.41 (s) 7.63 (s)
8.14 (s) 7.72 (s)
7.56 (s), 7.11
(
6.49 (br s) 4.19 (d, J¼12.9 Hz),
3.53 (d, J¼12.9 Hz)
29.9
d, J¼7.5 Hz),
6.83 (t, J¼7.5 Hz)
7.36 (s), 7.02
3316, 3286, 1750,
677, 1578
9.88 (s)
5.98 (br s) 4.43 (d, J¼13.2 Hz),
3.48 (d, J¼13.2 Hz)
d
1
(d, J¼7.2 Hz),
6
7.23 (s)
.86 (t, J¼7.2 Hz)
7
9
1
1
3439, 2962, 2874, 1676 9.93 (s)
d
7.57 (s)
6.47 (s)
6.37 (s)
d
4.37 (d, J¼11.4 Hz),
30.0
3
.30 (d, J¼11.4 Hz)
3437, 3284, 1751,
705, 1578
3384, 3268, 1749,
598, 1478
3424, 3278, 1750,
597, 1477
9.94 (s)
8.20 (s) 7.61 (s)
7.44 (s), 7.15 (s)
4.34 (d, J¼7.5 Hz),
3.48 (d, J¼7.5 Hz)
4.49 (br s), 3.42 (br s)
30.5
1
a
0
1
a
7.78 (br s) 7.95 (s) 7.78 (br s) 7.26 (br s), 7.02 (br s)
7.84 (s) 8.19 (s) 7.61 (s) 7.31 (s), 7.04 (br s)
1
d
4.55 (d, J¼13.5 Hz),
3.45 (d, J¼13.5 Hz)
31.2
1
13
C NMR spectral data could not be collected due to instability in solution.
Likewise, 4 exhibited signals at d 10.12 (s), 8.41 (s), 7.63
s), 6.49 (br s), and 3.94 (s) for NH, hydroxyl, CH, NH2,
and methoxy protons, respectively, while aromatic and methyl-
2.3. Interaction with anions
(
The anion co-ordination properties of the synthesized deriva-
1
tives were investigated by UVevis and H NMR spectro-
ene bridge protons could be observed at d 7.56 (s), 7.11 (d),
1
.83 (t), 4.19 (d), and 3.53 (d) in its H NMR spectrum indi-
6
cating that 4 is a distally disubstituted compound present in
its cone conformation with a symmetric configuration. A
scopic titrations in a DMSO solution. Various anions were
taken as tetrabutylammonium (TBA) salts. The unstable nature
of 10 in solution precluded the possibility of study of its utility
for anion recognition. Consequently, calix[4]arene semicarb-
azones (4, 7, and 9) were examined for preliminary UVevis
1
very similar H NMR spectral pattern was observed for 5. It
was interesting to note that 5 had two methyl ester functions
instead of ethyl ester functions present in the precursor com-
pounds as indicated by a singlet for six protons at d 3.88 in
ꢀ
ꢀ
studies. It was observed that the addition of TBA (Cl , Br ,
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
I , ClO , HSO , CH COO , and H PO ) salts did not lead
4
4
3
2
4
1
1
its H NMR. The H NMR spectral pattern of 9 also suggested
it to have a methyl ester function instead of the expected ethyl
ester units indicating that trans-esterification had occurred
with the methanol solvent present in excess. In addition to sin-
glets at d 9.94 (s), 8.20 (s), 7.61 (s), 6.37 (s), 4.86 (s), 3.80 (s),
and 1.09 (s) for NH, OH, CH, NH , ArOCH , OCH , and
to any change in the case of 4 and 9 while a significant increase
in absorption could be observed in the UVevis spectrum of 7
þ
ꢀ
when TBA $H PO was added to its DMSO solution (Fig. 1).
2
4
ꢀ
To test the practical utility of 7 as a H PO selective recep-
2
4
tor, competitive experiments were carried out by addition of
TBA salts in the presence of each other. These experiments re-
vealed that there was an increase in the absorption and a shift
2
2
3
C(CH ) protons, the two signals each for aromatic and meth-
3
3
þ
in the lmax of 7 upon addition of TBA $H PO even in the
2
ꢀ
ylene bridge protons could be observed at d 7.44 (s), 7.15 (s),
.34 (d), and 3.48 (d). Similarly, compounds 10 and 11 could
be characterized.
4
4
presence of halides and other anions while other receptor mole-
cules did not show such a differentiation.
1.50
1
1
1
1
1
0
0
0
0
0
0
0
0
0
.4
.3
.2
.1
.0
.9
.8
.7
.6
.5
.4
.3
.2
.1
-
L+H PO
L+Cl
2
4
-
-
L+CH COO
3
-
L+HSO4
-
L+I
-
L+Br
Ligand 7
0.00
255.0 280 300 320 340 360 380 400 420 440 460 480 500 520 540 560 580 600.0
NM
6
Figure 1. UVevis spectra of host 7(L) in DMSO-d on addition of excess TBA salts.

744
H.M. Chawla, S.P. Singh / Tetrahedron 64 (2008) 741e748
ꢀ
1
Anion recognition properties of 7 were further examined to
1
reveal that its H NMR spectra continuously changed upon ad-
dition of variable amounts of tetrabutylammonium dihydrogen
calculated as 1890 M from changes in chemical shift for
the NH protons of semicarbazone units by using WinEQNMR
program.
1
4 1
H NMR titration curve for observed change in
phosphate in DMSO-d while no spectral changes were ob-
chemical shift of NH proton of receptor 7 with tetrabutyl-
ammonium dihydrogen phosphate has been shown in Figure 3b.
The possibility of the presence of anion within the cavity of
receptor 7 could be ruled out on the basis of its CPK model,
which suggested that its cavity size was too small for
6
served upon addition of other tetrabutylammonium salts
ꢀ ꢀ ꢀ ꢀ
Cl , Br , I , ClO , and HSO ) under the same experimental
4
ꢀ
(
4
conditions (Fig. 2). In contrast, 4 and 9 were not found to ex-
1
hibit any change in their H NMR spectra even on addition of
ꢀ
tetrabutylammonium dihydrogen phosphate. These results
were found to be consistent with those observed in the UVe
vis spectral titration indicating the specificity of interaction
H PO anion. The experimental observations could be ex-
2
4
ꢀ
plained by assuming a four coordinate interaction of H PO
2
4
with NH protons at the upper rim of calix[4]arene through hy-
drogen bonds (Fig. 4a), which were further confirmed by NO-
ESY and ROESY experiments.
ꢀ
of 7 with H PO .
2
4
It was interesting to note that the NH signal at d 9.88 was
markedly affected by addition of tetrabutylammonium dihy-
The NOESY spectrum of a 1:1 solution of 7 and
þ
TBA $H PO revealed strong correlations between the
2
ꢀ
drogen phosphate to 7 in DMSO-d (Fig. 2). A significant
6
4
þ
downfield shift for NH proton and a marginal upfield shift
ꢀ
n-butyl chain of TBA and propoxy chain of calix[4]arene to
suggest the presence of TBA cation near the alkoxy group
(Fig. 4a and b). The ROESY spectrum, which seemed similar
to its NOESY spectrum further strengthened this view.
The similar experiments with the solution of 7 and
for aromatic protons suggested the proximity of H PO anion
2
4
ꢀ
to amidic functions and that the H PO anion is probably co-
4
2
ordinated by hydrogen bonds. No change in the CONH pro-
2
tons was observed, which indicated that these groups were
ꢀ
þ
ꢀ
not involved in the binding of H PO anion. The stoichiome-
2
TBA $PF also revealed correlations between n-butyl chain
4
6
ꢀ
þ
try of interaction of 7 and H PO was determined by Job’s
2
of TBA and propoxy chain of calix[4]arene. However, no
shift in the CH, NH, NH , and ArH protons suggested that
there was no effective binding of PF .
6
4
continuous variation plot. The results obtained unambiguously
indicated that a complex of unknown structure was formed be-
tween 7 and dihydrogen phosphate ion with a 1:1 stoichiome-
2
ꢀ
The above experiments revealed strong interaction between
adventitious water and CH, NH and NH protons and suggest
ꢀ
try (Fig. 3a). The association constant for 7 and H PO was
2
4
2
that water prefers to stay near the polar groups through hydro-
gen bond donoreacceptor mechanism. These observations are
in accordance with recent reports on the interaction of polar
solvents with polar groups at the upper rim of calix[4]arene,
which seems to play an important role in shaping the plausible
expansion of aromatic cavity through hydrogen bond
*+
*
++ +CH
(
(
a)
b)
3
ArCH Ar
2
ArH
OCH2
ArCH
CH2
NH
NH2
13
ArCH Ar
bridging.
2
It should be noted that both 4 and 9 were not able to bind
dihydrogen phosphate through only two semicarbazone units.
The observed high selectivity with 7 suggested a special inter-
action for diphosphate anion through hydrogen bonding over
ꢀ
ꢀ
ꢀ
other tetrahedral (ClO and HSO ), spherical (e.g., Cl ,
4
10
8
6
4
2
0
4
ꢀ
ꢀ
Br , and I ), and Y-shaped (e.g., acetate) anions, which calls
for further studies on anion recognition through calix[4]arene
based molecular receptors. Further work on this theme is in
progress in our labs.
1
Figure 2. H NMR (300 MHz) spectra of host 7 (10 mM) in DMSO-d
6
with
(significant downfield
ꢀ
(above) and without the addition of excess of H
shift in NH proton was observed, * indicate signal due to adventitious water
2
PO
4
þ
and residual solvent, þ indicate signals due to butyl protons of t-Bu
4
N
salt).
(a)
(b)
0
0
0
0
0
0
0
0
.8
.7
.6
.5
.4
.3
.2
.1
0
1
1
1
1
60
40
20
00
8
6
4
0
0
0
20
0
0
0.2
0.4
0.6
0.8
1
0
0.005
0.01
0.015
0.02
0.025
Mole fraction of anion
Concentration of anion
ꢀ
þ
1
salt). (b) H NMR titration curve
Figure 3. (a) Job’s plot of the titration of 0.01 M H
ꢀ
2
PO
4
with 0.01 M receptor 7 in DMSO-d
, 300 MHz, 298 K).
6
(anion used was in form of t-Bu
4
N
for NH proton of receptor 7 with TBA$H
2
PO
4
(DMSO-d
6

H.M. Chawla, S.P. Singh / Tetrahedron 64 (2008) 741e748
745
O
(a)
(b)
P
HO
OH
O
2
0
H
H
N
O
1
9
O
1
1
6 15
7 10,18
2
H N
H
H
R
1
N
NR
1
NH2
2
4
1
2
N
N
N
N
H
12 13
N
9
3
8
11
H
7
6
5
4
H
6
O
O O
O
H
8
6
NH -H O
7
2
2
CH
9
2
H C
4
5
2
11
0
1
3
CH-H O
8
2
CH3
8
1
17
R
2
1
9
2
0
N
R
12
16
R
2
13
1
5
1
4
1
2
NH-H O
10
2
2
ppm
R = -CONH2
1
R = -(CH ) CH
2
2 3
3
ppm 10
8
6
4
2
ꢀ
þ
ꢀ
4
PO (1:1) mixture in DMSO-d
Figure 4. (a) Proposed structure of host 7/H
2
PO
4
complex and observed NOESY correlations in 7/TBA $H
2
6
solution (intra-
molecular correlations have been shown in blue color while intermolecular correlations have been shown in green color, since molecule has 4-fold symmetry,
þ
ꢀ
ꢁ
correlation in only one fourth of the molecule have been shown). (b) NOESY spectrum of 7/TBA $H
300 MHz).
2 4 6
PO (1:1) mixture in DMSO-d solution at 25 C
(
3
. Conclusion
4.2. Synthesis of starting material
In summary, we have synthesized a series of new neutral
molecular receptors based on calix[4]arene framework. Recep-
p-tert-Butylcalix[n]arene, n¼4 and its debutylated analog
10a,b
were synthesized by the method described by Gutsche
ꢀ
tor 7 displays a high sensitivity and selectivity toward H PO
2
et al.
They were alkylated according to the literature pre-
4
anion in preference to a wide range of tetrahedral, spherical,
and Y-shaped anions.
cedent to yield desired 25,27-di(methoxy)-calix[4]arene,
25,27-di(ethoxycarbonylmethoxy)-calix[4]arene, 5,11,17,23-
tetra( p-tert-butyl)-25,27-di(ethoxycarbonyl methoxy)-calix[4]-
10ceh
arene, and 25,26,27,28-tetra(propoxy)-calix[4]arene.
These
4
. Experimental section
alkylated calixarene derivatives were further formylated by
Duff reaction protocol (as given in the following section) to
give the desired 5,11-bis(formyl)-25,27-di(methoxy)-26,28-di-
4
.1. General
(
hydroxy)-calix[4]arene (2), 5,11-bis(formyl)-25,27-di(ethoxy-
carbonylmethoxy)-26,28-di(hydroxy)-calix[4]arene (3), 5,11,
7,23-tetra(formyl)-25,25,26,27,28-tetra(propoxy)-calix[4]arene
6), and 5,11-bis(formyl)-17,23-di( p-tert-butyl)-25,27-di(eth-
All the reagents used in the study were purchased from Sig-
maeAldrich or Merck and were chemically pure. The solvents
1
used were distilled and dried except toluene and methanol. H
1
(
1
3
NMR, C NMR, DEPT-135, NOESY, and ROESY 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 recorded on a Nicolet
Prot e´ g e´ 460 spectrometer in KBr disks while 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 electro-
thermal melting point apparatus obtained from M/S Toshniwal
Brothers, Mumbai and were uncorrected.
1
1
oxycarbonylmethoxy)-26,28-di(hydroxy)-calix[4]arene (8).
4.3. General procedure for the synthesis of formylated
calix[4]arene derivatives (2, 3, 6, and 8)
Alkylated calix[4]arene (500 mg) and hexamethylenetetr-
amine (40 equiv) were taken in trifluoroacetic acid (50 mL).
The reaction mixture was refluxed until the starting materials
had disappeared (TLC, reaction time has been mentioned in

746
H.M. Chawla, S.P. Singh / Tetrahedron 64 (2008) 741e748
Scheme 1). On completion, the mixture was quenched with ice
cold water and extracted with dichloromethane. The organic
layer was washed with water and dried (Na SO ). The solvent
C H N O : C, 61.79; H, 6.48; N, 18.01. Found: C, 61.54;
48 60 12 8
H, 6.51; N, 17.89.
2
4
was evaporated under reduced pressure and the residue was
purified as mentioned to yield the desired formylated calix[4]-
arene products (2, 3, 6, and 8). The spectral data of the synthe-
sized formylated calix[4]arene derivatives were found to be
4
.4.4. Compound 9
White solid, yield: 86%, mp¼205 C. IR (KBr, n /cm ):
max
ꢁ
ꢀ1
1
437, 3284, 2925, 1751, 1705, 1578, 1470. H NMR
3
(300 MHz, DMSO-d , d in ppm): 9.94 (s, 2H, NH ), 8.20 (s,
1
1
6
similar to those reported earlier.
2H, OH ), 7.61 (s, 2H, CH ), 7.44 (s, 4H, ArH ), 7.15 (s, 4H,
ArH ), 6.37 (s, 4H, NH ), 4.86 (s, 4H, ArOCH ), 4.34 (d,
2
2
4
.4. General procedure for the synthesis of
J¼7.5 Hz, 4H, ArCH Ar), 3.80 (s, 6H, OCH ), 3.48 (d,
2
3
semicarbazone and hydrazone derivatives of
calix[4]arene
1
3
J¼7.5 Hz, 4H, ArCH Ar), 1.09 (s, 18H, C(CH ) ). C NMR
2
3 3
(
75 MHz, DMSO-d , d in ppm): 170.2, 157.6, 153.5, 150.9,
6
1
47.9, 140.9, 133.1, 129.4, 128.7, 127.4, 126.6 (C]O, CH,
To a solution of formylated calix[4]arene (200 mg) in
0 mL of toluene/methanol (1:1) was added a semicarbazi-
aromatic CH and C ), 72.0 (ArOCH ), 52.5 (OCH ), 34.4
2
3
4
de$hydrochloride or phenyl hydrazine derivative (1.1 equiv
(eC(CH ) ), 31.4 (eC(CH ) ), 30.5 (ArCH Ar). FABMS m/z:
3
3
3 3
2
þ
8
3
51 (M þ1). Anal. Calcd for C H N O : C, 55.63; H,
4
8 60 12 8
per one formyl group) and the mixture was refluxed for
1
.33; N, 9.27. Found: C, 55.54; H, 3.35; N, 9.34.
2 h. The solvent was then evaporated under reduced pressure
and the remaining solid was washed with methanol (for 7) or
water. The product was filtered and dried under vacuum to
give target products.
4.4.5. Compound 10
White solid, yield: 85%. IR (KBr, nmax/cm ): 3384, 3268,
ꢀ
1
1
930, 1749, 1598, 1478. H NMR (300 MHz, CDCl , d in
2
3
4
.4.1. Compound 4
Yellow colored solid, yield: 82%, mp>300 C (decomp.).
ppm): 7.95 (s, 2H, OH ), 7.78 (s, 4H, NH and CH ), 7.26 (br
s, 10H, ArH ), 7.02 (br s, 8H, ArH ), 4.83 (s, 4H, ArOCH2),
4.49 (br s, 4H, ArCH Ar), 4.33 (br s, 4H, CO(O)CH ), 3.42
ꢁ
ꢀ
1
IR (KBr, nmax/cm ): 3342, 2926, 1677. H NMR (300 MHz,
1
2
2
DMSO-d , d in ppm): 10.12 (s, 2H, NH ), 8.41 (s, 2H, OH ),
(br s, 4H, ArCH Ar), 1.35 (br s, 6H, CH CH ), 1.13 (s, 18H,
2 2 3
6
þ
7
.63 (s, 2H, CH ), 7.56 (s, 4H, ArH ), 7.11 (d, J¼7.5 Hz, 4H,
C(CH ) ). FABMS m/z: 945 (M þ1). Anal. Calcd for
58 64 4 8
3
3
ArH ), 6.83 (t, J¼7.5 Hz 2H, ArH ), 6.49 (br s, 4H,
C H N O : C, 73.70; H, 6.83; N, 5.93. Found: C, 73.46;
H, 6.86; N, 6.02.
meta
para
NH ), 4.19 (d, J¼12.9 Hz, 4H, ArCH Ar), 3.94 (s, 6H, CH ),
2
2
3
1
3
3
DMSO-d , d in ppm): 139.1, 128.8, 126.8, 125.1 (aromatic
.53 (d, J¼12.9 Hz, 4H, ArCH Ar). C NMR (75 MHz,
2
6
4
.4.6. Compound 11
Red solid, yield: 81%, mp¼218 C. IR (KBr, nmax/cm ):
CH and CH), 63.6 (OCH ), 29.9 (ArCH Ar). FABMS m/z:
3
2
ꢁ
ꢀ1
þ
6
5
23 (M þ1). Anal. Calcd for C H N O : C, 65.58; H,
3
4
34
6
6
1
424, 3278, 2930, 1750, 1597, 1477. H NMR (300 MHz,
3
.50; N, 13.50. Found: C, 65.91; H, 5.48; N, 13.45.
CDCl , d in ppm): 8.19 (s, 2H, OH ), 8.15 (d, 4H, J¼8.1 Hz,
3
ArH
), 7.84 (s, 2H, NH ), 7.61 (s, 2H, CH ), 7.31 (s, 4H,
phenyl
ArHcalix), 7.04 (br s, 8H, ArHphenyl and ArHcalix), 4.85 (s,
4
.4.2. Compound 5
White solid, yield: 84%. IR (KBr, nmax/cm ): 3316, 3286,
ꢀ
1
4
H, ArOCH ), 4.55 (d, J¼13.5 Hz, 4H, ArCH Ar), 4.37 (q,
1
2
2
2
926, 1750, 1677, 1578. H NMR (300 MHz, DMSO-d , d in
6
J¼6.9 Hz, 4H, CO(O)CH ), 3.45 (d, J¼13.5 Hz, 4H,
2
ppm): 9.88 (s, 2H, NH ), 8.14 (s, 2H, OH ), 7.72 (s, 2H, CH ),
.36 (s, 4H, ArH ), 7.02 (d, J¼7.2 Hz, 4H, ArHmeta), 6.86 (t,
J¼7.2 Hz, 2H, ArH ), 5.98 (br s, 4H, NH ), 4.75 (s, 4H,
ArCH Ar), 1.37 (t, 6H, J¼6.9 Hz, CH CH ), 1.15 (s, 18H,
2
2
3
7
13
C(CH ) ). C NMR (75 MHz, DMSO-d , d in ppm): 168.9,
3
3
6
para
2
1
1
53.0, 150.4, 150.3, 147.3, 141.7, 137.9, 132.2, 128.8, 127.6,
26.3, 125.9, 125.5, 110.3 (C]O, aromatic CH and C ), 71.4
ArOCH ), 4.43 (d, J¼13.2 Hz, 4H, ArCH Ar), 3.88 (s, 6H,
2
2
OCH ), 3.48 (d, J¼13.2 Hz, 4H, ArCH Ar). FABMS m/z:
3
2
(ArOCH2), 60.7 (CO(O)CH2), 33.6 (C(CH3)3), 31.2
þ
7
5
39 (M þ1). Anal. Calcd for C H N O : C, 61.78; H,
3
9 40 6 9
(
ArCH Ar), 30.63 (C(CH ) ), 13.6 (OCH CH ). FABMS
2
3 3
2
3
.18; N, 11.38. Found: C, 62.14; H, 5.16; N, 11.44.
þ
m/z: 1035 (M þ1). Anal. Calcd for C H N O : C, 67.30;
5
8 62 6 12
H, 6.04; N, 8.12. Found: C, 67.54; H, 6.01; N, 8.23.
4
.4.3. Compound 7
White solid, yield: 87%, mp>330 C (decomp.). IR (KBr,
ꢁ
ꢀ
1
nmax/cm ): 3439, 2962, 2874, 1676. H NMR (300 MHz,
1
4.5. General procedure for UVevis experiments
DMSO-d , d in ppm): 9.93 (s, 4H, NH ), 7.57 (s, 4H, CH ),
6
7
.23 (s, 8H, ArH ), 6.47 (s, 8H, NH ), 4.37 (d, J¼11.4 Hz, 4H,
All the UVevis experiments were carried out in dimethyl
sulfoxide. Any changes in the UVevis spectra of the synthe-
sized compound were recorded on addition of tetrabutylam-
monium salt (excess) while keeping the ligand concentration
constant in all experiments. Tetrabutylammonium salt of an-
2
ArCH Ar), 3.83 (br s, 8H, ArOCH ), 3.30 (d, J¼11.4 Hz, 4H,
2
2
ArCH Ar), 1.95 (br q, J¼6.3 Hz, 8H, ArOCH CH ), 0.99 (br
2
2
2
1
3
s, 12H, CH ). C NMR (75 MHz, DMSO-d , d in ppm):
3
6
1
56.8, 139.8, 134.5, 128.9, 126.8 (C]O, aromatic CH and
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
C ), 76.6 (OCH ), 30.0 (ArCH Ar), 22.7 (O CH CH ), 10.1
ions (Cl , Br , I , ClO , HSO , CH COO , and H PO )
4
2
2
2
2
4
3
2
4
þ
(
CH3). FABMS m/z: 933 (M þ1). Anal. Calcd for
was used for the UVevis experiments.

H.M. Chawla, S.P. Singh / Tetrahedron 64 (2008) 741e748
747
1
4
.6. General procedures for H NMR titration
Cambridge, UK, 1998; (c) Chakrabarti, A.; Chawla, H. M.; Pant, N.;
Singh, S. P.; Upreti, S. Tetrahedron 2006, 62, 8974e8981; (d) Chawla,
H. M.; Singh, S. P.; Upreti, S. Tetrahedron 2006, 62, 9757e9768; (e)
Chawla, H. M.; Hundal, G.; Singh, S. P.; Upreti, S. CrystEngComm.
4
.6.1. Interaction study
A solution of the hosts (4, 7, and 9) was prepared in
2
007, 9, 119e122; (f) Baldini, L.; Casnati, A.; Sansone, F.; Ungaro, R.
DMSO-d . To 0.5 mL of this solution, approximately 10 equiv
Coord. Chem. Rev. 2007, 36, 254e266; (g) Ludwig, R. Microch. Acta
2005, 152, 1e19.
3. (a) Chawla, H. M.; Singh, S. P.; Upreti, S. Tetrahedron 2006, 62, 2901e
6
ꢀ
ꢀ
ꢀ
ꢀ
of tetrabutylammonium salts of anions (Cl , Br , I , ClO ,
4
ꢀ
ꢀ
ꢀ
1
HSO , CH COO , and H PO ) were added in the H NMR
4
3
2
4
2
7
911; (b) Kumar, S.; Chawla, H. M.; Varadrajan, R. Tetrahedron 2003, 59,
481e7484; (c) Chakrabarti, A.; Chawla, H. M.; Francis, T.; Pant, N.;
tube and the spectra were recorded again. The chemical shift
of the NH protons was followed to observe significant change,
if any.
Upreti, S. Tetrahedron 2006, 62, 1150e1157; (d) Chawla, H. M.; Singh,
S. P.; Sahu, S. N.; Upreti, S. Tetrahedron 2006, 62, 7854e7865; (e)
Chawla, H. M.; Singh, S. P.; Upreti, S. Tetrahedron 2007, 63, 5636e
5642; (f) Arora, V.; Chawla, H. M.; Singh, S. P. ARKIVOC 2007, ii,
172e200; (g) Valeur, B.; Leray, I. Inorg. Chim. Acta 2007, 360, 765e
774; (h) Petrella, A. J.; Raston, C. L. J. Organomet. Chem. 2004, 689,
4
.6.2. Job plot
Solution of the host 7 (10 mM) and for the tetrabutylammo-
nium dihydrogen phosphate (10 mM) in DMSO-d were sepa-
4125e4136; (i) Valeur, B.; Leray, I. Coord. Chem. Rev. 2000, 205, 3e40.
4. (a) Beer, P. D.; Shade, M. Chem. Commun. 1997, 2377e2378; (b) Chawla,
H. M.; Sahu, S. N.; Shrivastava, R. Tetrahedron Lett. 2007, 48, 6054e
6
1
rately prepared. The H NMR tubes were filled with 500 mL
solution of host and the guest in the following volume ratios:
50:450, 100:400, 150:350, 200:300, 250:250, 200:300, 150:350,
6
058; (c) Schmidtchen, F. P. Coord. Chem. Rev. 2006, 250, 2918e2928.
5
. (a) Schmidtchen, F. P. J. Org. Chem. 1986, 51, 5161e5168; (b) Schiessel,
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Loeb, S. L. J. Am. Chem. Soc. 2004, 126, 5030e5031.
1
00:400, 50:450. The H NMR spectra of each tubes with above
1
mentioned ratio were recorded to observe significant shifts in
the position of NH protons in each experiment, which was plot-
ted to give the Job plot in accordance with recent literature
1
5
reports.
6
. Hosseini, M. W.; Blacker, A. J.; Lehn, J. M. J. Am. Chem. Soc. 1990, 112,
3
896e3904.
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.6.3. Association constant
A solution (10 mM) of receptor 7 in DMSO-d was titrated
2
6
with aliquots from stock solution of tetrabutylammonium di-
hydrogen phosphate (40 mM) in the same solvent. The chem-
ical shift change of the NH proton of semicarbazone units in
receptor 7 was monitored. The association constants K was
a
calculated using the WinEQNMR computer program.
2, 1582e1586; (d) Sessler, J. L.; Camiolo, S.; Gale, P. A. Coord. Chem.
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1
4
8
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Acknowledgements
We thank the C.S.I.R. for a senior research fellowship (to
SPS) and D.S.T; D.B.T., MOEF, MRD, and MFPI (Govt. of
India) for financial assistance. We also thank Sophisticated
Analytical Instrumentation Facility, Central Drug Research
Institute, Lucknow for the mass spectra reported in this paper.
9
Supplementary data
Supplementary data associated with this article can be
found in the online version, at doi:10.1016/j.tet.2007.11.010.
1
2, 53e65; (h) Evans, A. J.; Matthews, S. E.; Cowley, A. R.; Beer, P. D.
Dalton Trans. 2003, 24, 4644e4650.
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