Synthesis of tetrathiacalix[4]arene functionalised by acetylhydrazone fragments

Article abstract of DOI:10.1070/MC2006v016n06ABEH002404

The reactions of tetrathiacalix[4]arene functionalised by acetylhydrazide groups with an excess of 4-nitrobenzaldehyde or tetrathiacalix[4]arene functionalised by chlorocarbonylmethoxy groups with an excess of 4-nitrobenzaldehyde hydrazone lead to the pre

Full text of DOI:10.1070/MC2006v016n06ABEH002404

Mendeleev
Communications
Mendeleev Commun., 2006, 16(6), 297–299
Synthesis of tetrathiacalix[4]arene functionalised by acetylhydrazone fragments
Sergey N. Podyachev,*a Svetlana N. Sudakova,a Victor V. Syakaev,a Roald R. Shagidullin,a Azat K. Galievb and
Alexander I. Konovalova
a A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Centre of the Russian Academy of Sciences,
420088 Kazan, Russian Federation. Fax: +7 843 2755 322; e-mail: spodyachev@iopc.knc.ru
b Kazan State Technological University, 420015 Kazan, Russian Federation. Fax: +7 843 2752 253
DOI: 10.1070/MC2006v016n06ABEH002404
The reactions of tetrathiacalix[4]arene functionalised by acetylhydrazide groups with an excess of 4-nitrobenzaldehyde or
tetrathiacalix[4]arene functionalised by chlorocarbonylmethoxy groups with an excess of 4-nitrobenzaldehyde hydrazone lead to
the preferable formation of tetrathiacalix[4]arene with an additional N,N'-diacetylhydrazine bridge, but in the case of pyridine-
2-carboxaldehyde, only to the formation of tetrathiacalix[4]arene functionalised by four acetylhydrazone fragments.
Recently,1 we have reported the synthesis of a number of calix[4]-
arenes (calix[4]phenols, calix[4]resorcinols and calix[4]pyro-
gallols) functionalised by acetylhydrazide groups. On the basis
of them, new nitrogen-containing calix[4]arenes can be prepared.
It is known that acetylhydrazones can be obtained by the inter-
action of carboxylic acid hydrazides with aldehydes. Compounds
with such functional groups possess high complexability pro-
perties,2,3 which can be controlled by varying substituents in
the ylidene fragment during the synthesis procedure. Moreover,
acetylhydrazones and their complexes can exhibit biological
activity2 and serve as key reagents in the synthesis of hetero-
cyclic compounds.4 The introduction of these functional groups
into calixarene molecules could promote the preparing of effective
and highly selective complexones due to the macrocyclic co-
operative effect,5 as it was observed for calix[4]phenols modi-
fied by acetylhydrazide fragments.1 However, in spite of great
interest to the chemistry of calixarenes,6,7 there is no informa-
tion concerning acetylhydrazone derivatives on their basis. In
this connection, we have investigated the preparation of tetra-
thiacalix[4]phenols bearing acetylhydrazone groups.
For this purpose, the following two methods can be used
(Scheme 1). By the reaction of tetraester 1 with hydrazine
hydrate, tetrahydrazide 2 can be obtained. It would be expected
that the condensation of compound 2 with aldehyde would result
in the conversion of acetylhydrazide groups to acetylhydrazone
ones (method A). As the alternative approach, tetracarboxylic
acid 5, then the acid chloride 6 and the corresponding hydrazone
could be synthesised from ester 1 (method B).
During the reaction of calix[4]arene 2 with 4-nitrobenzalde-
hyde at room temperature in CHCl3 or at refluxing in ethanol
(method A, Scheme 1) and at the reaction of calix[4]arene 6
with 4-nitrobenzaldehyde hydrazone 7 (method B, Scheme 1),
precipitate formation was observed. We found that the azine
of 4-nitrobenzaldehyde 3 was a by-product of these reactions,
which was described previously.8 In both of the methods of
synthesis, the same composition precipitates have been isolated
after removing solvent from filtrate and repeated dissolution in
ethyl acetate. The most intense signal (m/z 1245 [M + H]+)
in the MALDI-TOF† mass spectra of reaction mixtures was
assigned to this isolated product. It was proposed that this mole-
cular peak in spectra corresponds to calix[4]arene 8 bearing two
4-nitrobenzaldehyde acetylhydrazone and two carboxymethyl
fragments (M = 1246). In the method A, its formation could
be caused by the hydrolysis of hydrazide groups in tetrathia-
calixarene 2. If we use synthetic method B, the hydrolysis of
1
unreacted chloranhydride groups could also take place. The H
and 13C NMR spectra are consistent with the structure proposed
for the isolated compound.
However, according to pH-potentiometry measurements, the
isolated product exhibits the properties of weak acids (pKa > 10)
in comparison with acid properties for the derivatives of
carboxylic acids (pKa ~ 5–6).9 Moreover, the elemental analysis
data show a higher content of nitrogen (9.03%) compared with
calculated (6.74%) for calix[4]arene having two 4-nitrobenz-
aldehyde acetylhydrazone and two carboxymethyl fragments.
Furthermore, no wide complicated Fermi resonance bands below
3000 cm–1, usually detected in carbonyl compounds,10 and
absorption bands of free vibrations νOH at ~3500 cm–1 are
observed in the IR spectra of dilute CHCl3 solutions. The
analysis of other ranges of spectra, where acid groups become
apparent, particularly νC–O, does not confirm their presence.
In this connection for an unambiguous identification of the
synthesised compound structure, we used a combination of
2D NMR spectroscopy methods [HSQC (13C and 15N) and HMBC
(13C and 15N)]. From the detailed investigation, it was established
that the isolated product corresponds to calix[4]arene 4, where
two opposite phenoxy fragments are additionally connected
by an N,N'-diacetylhydrazine bridge. If the bridge was formed
between two neighbouring phenoxy groups, the symmetry of
aromatic rings would be disturbed, which would lead to their
†
Mass spectra were detected on a Finnigan MALDI-TOF Dynamo
mass spectrometer. NMR spectra were recorded on Bruker Avance-600
(1H, 600 MHz; 13C, 150.9 MHz; 15N, 60.81 MHz) spectrometers. Chemical
shifts were reported relative to solvent signals as an internal standard
(CDCl3, dH 7.27 ppm, dC 77.7 ppm; DMSO, dH 2.5 ppm, dC 39.5 ppm).
The IR spectrum was recorded on a Bruker Vector instrument in Nujol.
Mendeleev Commun. 2006 297

Mendeleev Commun., 2006, 16(6), 297–299
(15N) spectra. According to published data,12 the nitrogen and
But
But
But
But
carbon chemical shifts are typical of the N,N'-diacetylhydrazine
fragment. The intensity of proton signals of the N,N'-diacetyl-
hydrazine fragment is the same in the solutions with different
polarity (CDCl3, DMSO) and in the wide concentration range.
This indicates that one of the amide fragments in the N,N'-di-
acetylhydrazine bridge has a trans conformation, but another
one shows a cis conformation.13 No considerable changes in the
νC=O (~1705 cm–1) absorption band frequencies were observed
in IR spectra in CHCl3 solutions under dilution. This is typical
of N,N'-diacetylhydrazine bridge containing compounds.14 The
presence of conformers about C(O)–N bond in N,N'-diacetyl-
hydrazine bridge, binding one pair of aromatic rings, as well as
in acetylhydrazone fragments, attached to another two aromatic
rings, leads to the appearance of four signals for tert-butyl
group protons and a number of signals for protons of aromatic
and amide fragments in NMR spectra.
NaOH, THF–H2O
But
But
S
S
But
But
S
S
O
O
O
O
O
O
O
O
S
S
S
O
O
O
O
S
O
O
O
O
1
O
O
HO
OH
O
O
OH
OH
NH2NH2, H2O,
EtOH, reflux
5
SOCl2, reflux
Calix[4]arene 4 can form as a result of an intramolecular
reaction.‡ Probably, the bonding of an aldehyde molecule
(method A) is accompanied by a nucleophilic attack of the
hydrazide group terminal nitrogen atom in calix[4]arene toward
the carbonyl group of neighbouring oppositely disposed hydrazide
or acetylhydrazone fragments, which leads to the formation of
intramolecular cross-links. The following reaction of hydrazine
or 4-nitrobenzaldehyde hydrazone with an excess of aldehyde
results in azine 3 formation, which precipitates during the process.
It is known that hydrazones are highly reactive compounds,
and under heating, moisture or catalyst effect they are capable
to change into azines with the liberation of hydrazine or into the
products of resinification.15,16 Indeed, the reaction of 4-nitro-
benzaldehyde hydrazone with calix[4]arene 6 (method B) is
accompanied by azine 3 formation. The interaction of hydrazine,
But
But
But
But
But
But
But
But
S
S
S
S
S
S
S
S
O
O
O
O
O
O
O
O
O
O
O
O
O
Cl
Cl
O
O
HN
O
NH
HN
NH2
Cl
NH
Cl
H2N
NH2
NH2
6
2
But
But
But
But
method A
O
method B
NH2
‡
Synthesis of 5,11,17,23-tetra-tert-butyl-25,27-bis[(4-nitrobenzylidene)-
N
hydrazinocarbonylmethyloxy]-26,28-[N,N'-hydrazinylene-bis(carbonyl-
methyleneoxy)]-2,8,14,20-tetrathiacalix[4]arene 4.
S
S
S
S
O
Method A. A solution of 4-nitrobenzaldehyde (1.64 mmol) in CHCl3
(10 ml) was added dropwise to a solution of tetrahydrazide 2 (0.4 mmol)
in CHCl3 (50 ml). The reaction mixture was stirred at room temperature
for 20 h. (Similar procedure was carried out in EtOH at the reflux for
5 h). The precipitate of 3 (mp 310 °C) was filtered off. After removing
the solvent from the filtrate under a reduced pressure, ethyl acetate (20 ml)
was added to the residue, and the mixture was heated. After cooling, the
precipitate was filtered off, washed several times with ethyl acetate and
O
O
O
NO2
O
O
O
HO
CHCl3, room
temperature
or
O
OH
NO2
HN
NH
7
N
pyridine,
THF, room
temperature
N
EtOH, reflux
1
recrystallised from EtOH–DMF. Yield 26%, mp 242–246 °C. H NMR
(600 MHz, [2H6]DMSO, 30 °C) d: 0.75 and 0.85 (s, 18H, But), 1.31 and
1.32 (s, 18H, But), 4.7–5.3 (m, 8H, OCH2), 6.8–7.0 (m, 4H, ArH),
7.8–8.4 (m, 12H, ArH), 9.3–9.9 (m, 2H, NHNH), 11.68 and 11.78 [2s,
2H, NHC(O)]. 13C NMR (150.9 MHz, [2H6]DMSO, 30 °C) d: 30.81,
30.85, 31.45 and 31.48 (Me), 34.09, 34.19, 34.61 and 34.77 (CMe3),
71.68, 73.13, 74.56 and 77.20 (OCH2), 128.39, 128.59, 157.86 and
157.95 [C(2) in 4-But-Ar], 132.29, 132.48, 132.95, 136.76, 136.96
and 137.23 [C(3) in 4-But-Ar], 146.89, 147.27, 147.48 and 148.26 [C(4)
in 4-But-Ar], 156.62, 156.27, 161.62 and 161.50 [C(1) in 4-But-Ar],
164.77, 166.25, 166.42, 169.66 and 171.55 (C=O). 15N NMR (60.81 MHz,
[2H6]DMSO, 30 °C) d: 121 and 122 (NHNH), 169 and 175 [NHC(O)],
321 and 322 (N=C), 366 (NO2). IR (n/cm–1): 3326, 3271, 3200 (νNH),
1707, 1680 (νC=O), ~1650 (sh, νC=N), ~1550 (sh, dNH (trans)), 1520
(νas NO ), 1342 (νs NO ), 1273, 1250 (nas COC), 1094 (ns COC), 835 (γ=CH).
NO2
O2N
8
But
But
But
But
NO2
S
S
S
S
O
O
O
O
N
O
O
O
+
O
N
HN
HN
NH
NH
2
N
2
MS (MALDI-TOF), m/z: 1245 [M + H]+, 1269 [M + Na]+, 1284 [M + K]+.
Found (%): C, 59.53; H, 5.72; N, 9.03; S, 10.02. Calc. for C62H66N8O12S4
(%): C, 59.88; H, 5.35; N, 9.01; S, 10.31.
N
Method B. A solution of 4-nitrobenzaldehyde hydrazone 7 (5 mmol)
in THF (25 ml) was added dropwise to a solution of calix[4]arene 6
(1.2 mmol) and pyridine (6 mmol) in THF (40 ml). The reaction mixture
was stirred at room temperature for 2 h. The precipitate of 3 was filtered
off. After removing the solvent from the filtrate under a reduced pressure,
CHCl3 was added to the residue, and the mixture was washed several
times with water. The organic layer was dried with MgSO4. After
removing the solvent from the filtrate under a reduced pressure, 30 ml of
ethyl acetate was added to the residue, and the mixture was heated. After
cooling, the precipitate was filtered off, washed several times with ethyl
acetate and recrystallised from EtOH–DMF. Yield 32%, mp 242–245 °C.
Found (%): C, 60.64; H, 5.54; N, 9.15, S, 10.10. Calc. for C62H66N8O12S4
(%): C, 59.88; H, 5.35; N, 9.01; S, 10.31. The IR and NMR spectra of
compound 4 obtained by methods A and B are identical.
NO2
NO2
O2N
3
4
Scheme 1
magnetic non-equivalence and as a result to the splitting of
1
aromatic proton signals in H NMR spectra with the coupling
constants 4J ~ 1–3 Hz.11 Such a phenomenon has not been
observed. The N,N'-diacetylhydrazine bridge formation has
been proved by the presence of cross peaks between nitrogen
(122 ppm) and NH group protons (~9.5 ppm) in HSQC (15N)
spectra and with oxymethyl protons (4.86 and 5.0 ppm) in HMBC
298 Mendeleev Commun. 2006

Mendeleev Commun., 2006, 16(6), 297–299
This work was supported by the Russian Foundation for Basic
Research (grant no. 04-03-32992).
But
But
But
But
References
1
S. N. Podyachev, V. V. Syakaev, S. N. Sudakova, R. R. Shagidullin,
D. V. Osyanina, L. V. Avvakumova, B. I. Buzykin, Sh. K. Latypov,
V. D. Habicher and A. I. Konovalov, J. Incl. Phenom., 2006, in press.
V. A. Kogan, V. V. Zelentsov, G. M. Larin and V. V. Lukov, Kom-
pleksy perekhodnykh metallov s gidrazonami (Complexes of Transition
Metals with Hydrazones), ed. A. Yu. Tsivadze, Nauka, Moscow, 1990,
p. 112 (in Russian).
K. Andjelkovic, M. Sumar and I. Ivanovic-Burmazovic, J. Thermal
Analysis and Calorimetry, 2001, 66, 759.
Yu. P. Kitaev and B. I. Buzykin, Gidrazony (Hydrazones), ed. A. N.
Kost, Nauka, Moscow, 1974, p. 416 (in Russian).
A. I. Konovalov, I. S. Antipin, A. R. Mustafina, S. E. Solov’eva and
S. N. Podyachev, Koord. Khim., 2004, 30, 243 (Russ. J. Coord. Chem.,
2004, 30, 227).
C. D. Gutsche, Calixarenes Revisited: Monograph in Supramolecular
Chemistry, ed. J. F. Stoddart, Royal Society of Chemistry, Cambridge,
1998, p. 233.
S
S
S
S
O
O
O
O
2
O
N
O
N
O
HN
NH
O
NH
HN
N
N
3
4
5
X
X
X
X
R
R
R
R
6
9 X = C, R = NO2
10 X = N, R = H
7
8
9
Calixarenes, eds. Z. Asfari, V. Böhmer, J. Harrowfield and J. Vicens,
Kluwer Academic, Dordrecht, 2001, p. 684.
R. Cremlyn, F. Swinbourne, S. Plant, D. Saunders and C. Sinderson,
Phosphorus Sulfur Relat. Elem., 1981, 10, 323.
L. Eberson, in The Chemistry of Carboxylic Acids and Esters, ed. S. Patai,
Interscience, New York, 1969, p. 272.
released during the process, with two oppositely located C(O)Cl
groups of calix[4]arene 6 leads to the intramolecular N,N'-di-
acetylhydrazide bridge formation.
The low-intensity molecular peak (m/z 1541 [M + H]+) was
found in the MALDI-TOF mass spectra of the reaction mixture
(method B), which can be explained by the presence of calix-
[4]arene 9 (M = 1540). We failed to isolate 9 as an individual
product.
10 L. J. Bellamy, The IR Spectra of Complex Organic Molecules, 2nd edn.,
Methuen, London, Wiley, New York, 1958, p. 425.
11 F. Narumi, N. Morohashi, N. Matsumura, N. Iki, H. Kameyama and
S. Miyano, Tetrahedron Lett., 2002, 43, 621.
12 H. Fritz, H. Kristinsson, M. Mollenkopf and T. Winkler, Magn. Reson.
Chem., 1990, 28, 331.
13 V. V. Syakaev, S. N. Podyachev, B. I. Buzykin, Sh. K. Latypov, V. D.
Habicher and A. I. Konovalov, J. Mol. Struct., 2006, 788, 55.
14 M. Mashima, Bull. Chem. Soc. Jpn., 1962, 35 (2), 32.
15 V. Z. Shirinian, L. I. Belen’kii and M. M. Krayushkin, Izv. Akad. Nauk,
Ser. Khim., 1995, 2197 (Russ. Chem. Bull., 1995, 44, 689).
16 H. Szmant and C. McGinnis, J. Am. Chem. Soc., 1950, 72, 2890.
17 E. A. Alyeksyeyeva, S. S. Basok and A. I. Gren, Mendeleev Commun.,
2005, 122.
The test reaction with benzaldehyde (method A) in CHCl3
showed that the most intense peak in MALDI-TOF mass spectra
corresponds to a product similar to 4. At the same time, the use
of pyridine-2-carboxaldehyde as a reagent leads to the disap-
pearance of the molecular peak corresponding to the compound
similar to 4 from the MALDI-TOF spectra of the reaction mix-
ture. Instead of it, the desired product (tetrahydrazone 10) was
isolated in a quantitative yield.§ It is known that nitrogen in
the pyridine ring is one of the strongest proton acceptors.10
Obviously, the formation of an intramolecular hydrogen bond
between nitrogen of pyridine ring and the NH group of the
neighbouring acetylhydrazone fragment or with the NH group
of the fragment in ZC=N isomer prevents from breakage of
amide bond and facilitates the formation of tetrathiacalix[4]arene
10 bearing four acetylhydrazone groups.
Thus, the formation of the acetylhydrazone derivatives of
tetrathiacalix[4]arene has been studied. In particular, the unusual
formation of an N,N'-diacetylhydrazine bridge in the calixarene
structure has been discovered. The synthesis of similar calix(aza)-
crown compounds is of interest in the context of obtaining high
selectivity complexones.17
§
Synthesis of 5,11,17,23-tetra-tert-butyl-25,26,27,28-tetrakis[(2-pyridi-
nylidene)hydrazinocarbonylmethyloxy]-2,8,14,20-tetrathiacalix[4]arene
10. A solution of pyridine-2-carboxaldehyde (1.64 mmol) in ethanol
(10 ml) was added dropwise to a solution of tetrahydrazide 2 (0.4 mmol)
in ethanol (10 ml). The reaction mixture was stirred at room temperature
for 1 h and then refluxed for 5 h. After removing the solvent, hexane
(20 ml) was added to the residue, and the mixture was heated. After
cooling, the precipitate was filtered off, washed several times with
hexane and recrystallised from MeOH. Yield 80%, mp 190–195 °C.
1H NMR (600 MHz, [2H6]DMSO, 30 °C) d: 1.12 (s, 36H, But), 5.37 (s,
8H, OCH2), 7.14 [s, 4H, C(3) in 4-But-Ar], 7.28 [s, 4H, C(4) in 2-Py],
7.68 [s, 4H, C(5) in 2-Py], 7.81 [s, 4H, C(6) in 2-Py], 8.36 (s, 4H, N=C–H),
8.52 [s, 4H, C(3) in 2-Py], 11.3 (s, 4H, NH). 13C NMR (150.9 MHz,
[2H6]DMSO, 90 °C) d: 30.12 (Me), 33.11 (CMe), 71.99 (OCH2), 119.40
[C(6) in 2-Py], 123.18 [C(4) in 2-Py], 127.84 [C(2) in 4-But-Ar], 133.66
[C(3) in 4-But-Ar], 135.57 [C(5) in 2-Py], 145.87 [C(4) in 4-But-Ar],
148.49 [C(3) in 2-Py], 152.64 [C(1) in 2-Py], 157.34 [C(1) in 4-But-Ar],
168.66 (C=O). IR (n/cm–1): 3232 (νNH), 3069 (ν=CH), 2961–2870 (νMe
,
ν
CH ), 1690 (νC=O), ~1650 (sh, νC=N), 1614, 1586, ~1450 (νPh), ~1557,
15420 (δNH ), 1362, 1349 (σMe), 1266, 1243 (νas COC), 1095 (νs COC),
trans
749 (γ=CH). MS (MALDI-TOF), m/z: 1390 [M + Na]+, 1412 [M + 2Na]+,
1430 [M + Na + K]+. Found (%): C, 63.57; H, 5.86; N, 11.60; S, 9.78.
Calc. for C72H76N12O8S4 (%): C, 63.32; C, 5.61; N, 12.31; S, 9.39.
Received: 7th July 2006; Com. 06/2749
Mendeleev Commun. 2006 299