The conformation and dynamic behaviour of tetrathiacalix[4]arenes functionalized by hydrazide and hydrazone groups

Article abstract of DOI:10.1016/j.molstruc.2007.10.016

The ¹H, ¹³C and ¹⁵N NMR data, conformation and dynamic behaviour of the new tetrathiacalix[4]arenes functionalized by hydrazide and hydrazone groups are reported and compared with the result of earlier investigations of 4-

Full text of DOI:10.1016/j.molstruc.2007.10.016

Available online at www.sciencedirect.com
Journal of Molecular Structure 885 (2008) 111–121
www.elsevier.com/locate/molstruc
The conformation and dynamic behaviour of
tetrathiacalix[4]arenes functionalized by hydrazide
and hydrazone groups
Victor V. Syakaev *, Sergey N. Podyachev, Aidar T. Gubaidullin,
Svetlana N. Sudakova, Alexander I. Konovalov
A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center of Russian Academy of Sciences, Arbuzov Str., 8, 420088 Kazan, Russia
Received 6 July 2007; received in revised form 10 October 2007; accepted 18 October 2007
Available online 26 October 2007
Abstract
The 1H, 13C and 15N NMR data, conformation and dynamic behaviour of the new tetrathiacalix[4]arenes functionalized by hydrazide
and hydrazone groups are reported and compared with the result of earlier investigations of 4-tert-butylphenoxyacetylhydrazones. The
unusual fact of formation of N,N0-diacetylhydrazine bridge and factors leading to its formation in the cone conformer of calixarene has
been discussed. The barriers of rotation of hydrazone fragments of tetrathiacalix[4]arenes were determined by NMR-measurements at
various temperatures. The structure of 1,3-alternate conformer of 5,11,17,23-tetra-tert-butyl-25,26,27,28-tetrakis[hydrazinocarbonylm-
ethyl]-2,8,14,20-tetrathiacalix[4]arene in solution is compared with crystal structure obtained by the X-ray analysis.
Ó 2007 Elsevier B.V. All rights reserved.
Keywords: Calix[4]arene; Hydrazide; Hydrazone; NMR spectroscopy; X-ray crystallography
1. Introduction
binding center and provides their unique complexation
properties [8]. The comparison of extraction properties of
synthesized calix[4]phenol derivatives and their acyclic
monomeric analogue has clear showed, that the preorgani-
zation of acetylhydrazide groups on the calix[4]arene plat-
form is the cause of dramatic improvement of their binding
ability [9]. The presence of additional ‘‘soft” nitrogen atom
in ion-binding sites of acetylhydrazide derivatives of
calix[4]arenes leads to the shift of classical selectivity from
alkali and alkaline earth cations which is observed for
amide derivatives to transitional metal ions.
It is known that hydrazides of carboxylic acids are key
reagents for the synthesis of other nitrogen containing
derivatives, particularly, acylhydrazones [10,11]. The con-
densation of hydrazides with aldehydes leads as a rule to
the conversion of acetylhydrazide groups to acetylhydraz-
one ones. Thus, the acetylhydrazones (4,5) (see Fig. 1) have
been obtained on the base of 4-tret-butylphenoxyacetylhyd-
razide (1), which is the monomer structure block of tetra-
hydrazide derivatives of calix[4]phenols (2,3) [12,13].
In the last decades it has been shown that preorganiza-
tion plays a fundamental role in molecular recognition
[1,2]. Preorganization and rigidity of host molecules are
usually obtained by covalent linking of binding groups
by means of rigid spacers to suitable templates [3,4].
Calix[4]arenes are very interesting host molecules and their
complexation ability can be varied either by changing the
nature and the number of the binding sites located on both
rims or by controlling the conformation of the calix[4]arene
molecule [1,5,6].
To investigate this problem the series of new calix[4]phe-
nols, calix[4]resorcinols and calix[4]pyrogallols with acety-
lhydrazide substituents has been designed and synthesized
[7]. The presence of carbonyl oxygen and amine nitrogen
atoms in acylhydrazides promotes the formation of chelate
*
Corresponding author. Tel.: +7 843 2727484; fax: +7 843 2731872.
E-mail address: vsyakaev@iopc.knc.ru (V.V. Syakaev).
0022-2860/$ - see front matter Ó 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2007.10.016

112
V.V. Syakaev et al. / Journal of Molecular Structure 885 (2008) 111–121
Fig. 1. Compounds investigated. Numbering system used in Tables.
However, the reaction of tetrathiacalix[4]arene 2 with an
excess of 4-nitrobenzaldehyde leads to the preferable forma-
tion of unconventional tetrathiacalix[4]arene (6) with addi-
tional N,N0-diacetylhydrazine bridge [14]. The calix[4]arene
6 is formed as a result of intramolecular reaction. When
using of pyridine-2-carboxaldehyde as a reagent, only for-
mation of tetrathiacalix[4]arene functionalized by four acet-
ylhydrazone fragments has been observed (7) [14].
[7,9,14] we present therein the results of the complete
assignment of 1H, 13C and 15N NMR spectra and the inves-
tigation of conformational and dynamic behaviour of these
compounds. The conformation of 3 in solution is com-
pared with the structure obtained by the X-ray analysis.
2. Experimental
The properties and reaction ability of compounds are
determined in many cases by their conformation and/or
configuration [15]. It is generally known that the energies
of conformational transitions in organic molecules are
too small in comparison with activation energy of chemical
reactions. Therefore, the conformational effects usually
influence weakly on the reaction rate and its direction.
However, in the large molecules, especially in supramole-
cules, the influence of weak effects can be considerably
increased by cooperative interactions in these molecules.
The hydrogen bonds determine intramolecular interac-
tions, the self-assembly of supramolecular structures and
also effect on the conformational properties of molecules.
Therefore, the conformational and hydrogen bonding con-
trol is a rational way to predict the physical and chemical
behaviour of the molecules.
2.1. Materials and methods
All reagents were used as commercially received without
further purification. CDCl3 (99.8% isotopic purity) and
DMSO-d6 (99.5% isotopic purity) from Aldrich were used
for NMR spectroscopy. Microanalyses of C, H, N were
carried out with a CHN-S analyzer (Carlo Erba). The IR
spectra were recorded on a Vector-22 Bruker FT-IR spec-
trophotometer using KBr pellets with a resolution of
4 cmꢀ1. Mass spectra were detected on a Finnigan
MALDI-TOF Dynamo mass spectrometer.
The hydrazides 1–3 and hydrazones 4–7, the derivatives
of 4-tert-butylphenoxyacetylhydrazide 1 and tetrathiaca-
lix[4]arene 2, were obtained as described earlier [7,9,12,14].
2.1.1. N,N0-di(4-tert-butylphenoxyacetyl)hydrazine 8
To the 4-tert-butyl-phenoxyacetyl hydrazide 1 (0.22 g;
1 mmol) in water (5 ml) under stirring HCl solution
(37%, 0.09 ml; 1 mmol) was added. The reaction mixture
Following to our previous studies on reactivity and
binding properties of tetrathiacalix[4]arenes functionalized
by hydrazide and hydrazone groups synthesized earlier

V.V. Syakaev et al. / Journal of Molecular Structure 885 (2008) 111–121
113
was refluxed for 2 h. The solid remainder was formed, fil-
tered off and washed by water, then by diethyl ether. The
product was obtained as a white powder. Yield 69%, mp
156–158 °C. IR (m/cmꢀ1, KBr): ꢁ3250 (mNH); ꢁ3050
(mCH); 3000–2850 (mCH3, mCH2); 1709, 1639 (mC@O);
1608 (mPh); 1513 (dNH (trans)); 1500–1350 (dCH3,
dCH2); 1246, 1185, 1071 (mCO, mCN, mNN, mCC); 830
(cCH-para); 551 (dC@O). Elemental analysis Calcd. for
C24H32N2O4: C, 69.88; H, 7.82; N, 6.79. Found: C, 70.27;
H, 8.16; N, 6.41.
2.2. X-ray crystallography
The crystal data for the compound 3 were collected on
the CAD 4 Enraf-Nonius diffractometer (graphite mono-
˚
chromated Cu Ka radiation, k = 1.54184 A) [16]. The sta-
bility of the crystal and experimental conditions was
checked every 2 h using three control reflections, while
the orientation was monitored every 200 reflections by cen-
tering two standards. No significant decay was observed.
Corrections for Lorentz and polarization effects and
absorption correction were applied. The structure was
solved by direct methods using SIR [17]. Full-matrix
least-squares refinement on F2 was performed in SHEL-
XL-97 [18] with anisotropic displacements for non-H
atoms. All hydrogen atoms (excluding H atoms of NH
and NH2-groups) were placed in idealized positions and
refined by using the riding model. Hydrogen atoms of
NH and NH2-groups, located in DF maps, were refined
as riding atoms (for NH groups) and were included into
structure factor calculations with fixed positional and ther-
mal parameters (for NH2 groups). Illustrations were made
using Platon [19]. Crystallographic data for the structure
were deposited in the Cambridge Crystallographic Data
Centre (deposition number CCDC 651590).
2.2.1. Crystal data
C48H64N8O8S4, H2O, M = 1027.33 g molꢀ1, colorless
prism of dimensions 0.4 ꢂ 0.3 ꢂ 0.1 mm3, monoclinic,
˚
a = 15.506(3), b = 12.9387(13), c = 29.664(6) A, b =
3
˚
100.45(2)°, V = 5852.7(18) A , T = 293 K, space group
P21/n, Z 4, l(Cu Ka) 19.38 cmꢀ1, dcalc = 1.166 g cmꢀ3
.
11183 reflections measured, 10974 unique (Rint = 0.046),
5965 observed with F2 > 2rI, 647 parameters, 83 restraints.
The final R1(F2) was 0.0897 (>2rI) and wR2 (all data) =
0.3009. Goodness-of-fit on F2 was 1.032, largest diff. peak
3
˚
and hole are 0.014 and ꢀ0.009 e A .
2.3. NMR spectroscopy
NMR spectra were recorded on a Bruker AVANCE-600
spectrometer (1H at 600.13 MHz, 13C at 150.864 MHz, 15
N
at 60.81 MHz) at 303 K. Chemical shifts in H and 13C
spectra (Tables 1 and 2) were reported relative to the sol-
vent as internal standard (CDCl3 d(1H) = 7.27 ppm,
d(13C) = 77.2 ppm; DMSO d(1H) = 2.50 ppm, d(13C) =
39.5 ppm). The 15N NMR spectra referenced to external
1

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V.V. Syakaev et al. / Journal of Molecular Structure 885 (2008) 111–121
urea and converted to the liquid anhydrous ammonia scale
((NH2)2C(O) d(15N) = 75 ppm). The pulse programs of the
NOESY, HSQC and HMBC experiments were taken from
Bruker software library.
all groups. The absence of methylene bridges, the carbon
signals of which are used for conformational structure
assignment of classical calix[4]arenes [21], makes the deter-
mination of the conformation of thiacalix[4]arene deriva-
tives more difficult. To distinguish between two
conformers (cone or 1,3-alternate) a NOESY experiments
were carried out. Strong NOE coupling between the pro-
tons of tert-butyl and aromatic groups, weak interaction
between amide and OACH2 groups and the absence of
any coupling between protons of these groups with aro-
matic or tert-butyl protons indicates the cone conformation
for 2. The 1,3-alternate conformation of 3 has been unam-
biguously proven by finding of NOEs of methylene and
amide protons with protons of aromatic and tert-butyl
groups i.e. between up and low rim substituents. These
conclusions have been also supported by the consideration
of chemical shifts of methylene protons: 4.86 and 4.36 ppm
for compounds 2 and 3, respectively. In 1,3-alternate con-
formation these protons are in a shielding field of two adja-
cent phenyl groups so they should resonate at a higher field
than those of the cone conformer.
2.4. Molecular calculations
Molecular structure was optimized by semi-empirical
geometry optimization (AM1) incorporated in the Hyper-
Chem7.03 program package [20].
3. Results and discussion
X-ray analysis has revealed that in the crystal of the
compound 3 there is one water molecule per molecule of
the macrocycle. The macrocycle 3 adopts 1,3-alternate con-
formation, where opposite phenyl rings of the basic macro-
cycle form the dihedral angles 53.0(3)° and 47.9(2)° (see
Fig. 2). Two adjacent hydrazide fragments are directed into
the cavity of calix[4]arene molecule, thus the solvate water
molecule is located outside the cavity. Three of tert-butyl
groups are disordered on two positions. The non-hydrogen
atoms of the acetylhydrazide groups are practically at the
same plain, meanwhile all acetylhydrazide fragments have
trans-amide conformation. The trans-amide configuration
of acetylhydrazide fragments can be stabilized by intramo-
lecular hydrogen bonds between the amide hydrogen atom
and the oxygen atom of the phenoxy group. However, this
stabilization is observed only for one of two acetylhydraz-
ide fragments disposed on each side of calix[4]arene mole-
cule. Formation of intramolecular hydrogen bond for
another neighboring acetylhydrazide group is impossible
because of sterical hindrances in the molecule. It is the rea-
son why not all hydrazide hydrogen atoms in crystal are
involved in hydrogen bonding.
The presence of C(O)AN bond in a molecule may lead
to the existence of amide conformers. The hydrazide
groups in the compounds 1–3 adopt preferentially trans-
conformation with the percentage 98–100%. The assign-
ments of cis/trans-rotamers have been made from NMR
spectroscopic data on the base of ideology described in
our previous work [13]. Geminal proton–carbon coupling
2
constants JC(O),NH have values 7.8 Hz for 2 and 9.0 Hz
3
for 3. Vicinal coupling constants JOCH ;NH in both cases
2
have not been resolved (3J < 0.3 Hz). These values of con-
stants are in good agreement with ones observed for 4-tert-
butylphenoxyacetylhydrazones [13]. Moreover, NMR
spectroscopic investigations are in accordance with X-ray
analysis data, obtained for 1 and 3 in solid state: the values
of torsion angle C(O)ANH are 179.4 0.3° [12] and
177.2–179.6° (estimated from angle value C(O)ANAN)
correspondingly.
Due to the NAHꢃꢃꢃN interactions the centrosymmetrical
0
˚
H-dimer is formed. (see Fig. 2) (d(H45BꢃꢃꢃO30 ) = 2.37 A,
0
d(N45ꢃꢃꢃO30 ) = 3.21(1) A,
\(N45-H45BꢃꢃꢃO300) = 154°,
˚
ꢀx, ꢀy, ꢀz). The participation of water molecules in
hydrogen bonding leads to the binding of dimers in two
perpendicular directions and as a result to the formation
of H-bonded molecular layers parallel to the plane 101.
Any particular interactions (including p–p contacts)
between these layers are not observed. It should be noted
that p–p contacts are not observed in the crystal in a whole,
what can be also explained by sterical hindrances.
In CDCl3 solution the chemical shift of amide (NH) pro-
tons of cone conformer 2 is considerably larger than that
for 1,3-alternate conformer 3 (9.88 and 7.36 ppm corre-
spondingly). Moreover, the chemical shift of amide (NH)
protons of
2
does not depend on the solvent
(d(CDCl3) = 9.88 ppm versus d(DMSO) = 9.87 ppm). Tak-
ing into account, that the similar proton in model com-
pound 1 resonates in different ways (d(CDCl3) = 7.9 ppm
versus d(DMSO) = 8.9 ppm), we have concluded that there
is probably a strong circular intramolecular hydrogen bond
between all NHꢃꢃꢃO@C groups at the low rim of tetrathi-
acalix[4]arene 2. The molecular structure of hydrazide 2
as obtained by semi-empirical geometry optimization
(AM1) also indicates on the possible realization of circular
Parallel packing of the above mentioned layers in the
crystal results in localization of the hydrophobic tert-butyl-
and aromatic groups on the external sides of these layers
(see Fig. 3). It is interesting to note that in this case the
large cavities, potentially accessible for solvent molecules,
are observed. The total volume of these cavities in the unit
3
˚
cell equals to 865.2 A . This fact can be explained by the
intramolecular
hydrogen
bonding
AC(O)ꢃꢃꢃHNA
˚
˚
presence in crystal of high disordered water molecules.
The 1H NMR spectra of 2 and 3 in DMSO at 303 K has
showed that these compounds possess highly symmetrical
structures. Those spectra contain only single signals for
(2.13–2.18 A) and AHNHꢃꢃꢃNH2 (2.52–2.54 A) (see Fig. 4).
More significant distinctions in the behavior of cone 2
and 1,3-alternate 3 conformers were observed under the
heating of DMSO solutions. Additional signals (see

Table 2
13C chemical shifts (ppm) of acetylhydrazides 1–3 and trans-(cis-) conformers of acetylhydrazones 4–9
Compound: 1
2
3
4
5
6
7a
DMSO DMSO
8
9
Solvent:
DMSO
CDCl3
DMSO
CDCl3
DMSO
DMSO
DMSO
DMSO
DMSO
b
c
d
c
C1
C2
C3
C4
C5
C6
C7
C8
N9
N10
C11
C12
C13
C14
C15
C16
a
31.37 (ꢀ)e 31.26 (ꢀ)e 31.22 (ꢀ)e 31.54 (ꢀ)e 30.78 (ꢀ)e 31.28 (31.30)
33.84 (ꢀ)e 34.52 (ꢀ)e 34.41 (ꢀ)e 34.79 (ꢀ)e 33.92 (ꢀ)e 33.77 (33.71)
31.27 (ꢀ)e
30.81 (30.85)
34.19 (34.09)
31.45 (31.48)
34.77 (34.61)
30.12 31.26 (ꢀ)e 30.49 (ꢀ)e
33.11 33.75 (ꢀ)e 33.80 (ꢀ)e
31.07 (31.10)
34.41 34.25)
148.48 (ꢀ)e
33.75 (33.70)
143.45 ꢀ)e 148.29 (ꢀ)e 147.32 ꢀ)e 149.04 ꢀ)e 147.48 ꢀ)e 143.55 (142.95) 143.53 (142.95) 147.27 146.89) 148.28 147.48) 145.87 143.41 (ꢀ)e 146.93 ꢀ)e
126.12 (ꢀ)e 135.21 (ꢀ)e 135.03 (ꢀ)e 128.80 (ꢀ)e 127.74 (ꢀ)e 126.10 (125.95) 126.09 (125.94) 132.48 (132.29) 137.23 (136.76) 133.66 125.99 (ꢀ)e 132.10 132.35 136.77 (136.43)
114.19 (ꢀ)e 128.55 (ꢀ)e 128.89 (ꢀ)e 127.47 (ꢀ)e 126.76 (ꢀ)e 114.19 (113.96) 114.14 (113.96) 128.39 (128.59) 157.86 (157.95) 127.84 114.18 (ꢀ)e 128.15 128.24 129.17 (130.47)
155.62 (ꢀ)e 158.40 (ꢀ)e 158.43 (ꢀ)e 155.01 (ꢀ)e 154.37 (ꢀ)e 155.49 (155.89) 155.46 (155.87) 156.62 (156.27) 161.62 (161.50) 157.34 155.47 (ꢀ)e 155.99 (ꢀ)e
157.34 (161.01)
76.66 (71.17)
166.17 (171.16)
126 (123)
66.32 (ꢀ)e 75.37 (ꢀ)e 74.36 (ꢀ)e 68.62 (ꢀ)e 67.38 (ꢀ)e 66.60 (64.64)
66.543 (64.685) 74.56 (73.13)
71.68 (77.20)
71.99 66.05 (ꢀ)e 74.24 (ꢀ)e
166.55 (ꢀ)e 169.14 (ꢀ)e 167.86 (ꢀ)e 168.30 (ꢀ)e 165.08 (ꢀ)e 164.81 (169.39) 164.91 (169.57) 164.77 (169.66) 166.25 (171.55) 168.66 166.83 (ꢀ)e 166.58 (ꢀ)e
135 (ꢀ)e
54 (ꢀ)e
126 (ꢀ)e
53 (ꢀ)e
125 (ꢀ)e
52 (ꢀ)e
132 (ꢀ)e
52 (ꢀ)e
169 (175)
322 (321)
122 (121)
173
318
125 (ꢀ)e
126 (ꢀ)e
(ꢀ)e
148.11 (144.21) 145.42 (141.38) 145.64 (142.16)
153.05 (152.81) 140.40 (140.23) 140.88 (140.59)
119.94 (119.78) 128.02 (127.82) 128.59 (128.28)
136.83 (136.76) 123.97 (123.91) 124.48 (124.48)
124.46 (124.28) 147.90 (147.72) 148.44 (148.26)
149.48 (149.42)
148.49
152.64
148.49
124.38
135.57
119.40
Spectra at 393 K.
For acetylhydrazone containing fragments.
For N,N0-diacetylhydrazine containing fragment.
For acetylhydrazide containing fragments.
Signal not assigned as it was covered by other signals or due to low concentration of conformer.
b
c
d
e

116
V.V. Syakaev et al. / Journal of Molecular Structure 885 (2008) 111–121
2
D* 9 þ NH2NH2
)
RT
Similar process takes place, for example, at the sponta-
neous dimerization of trifluoroacetyl hydrazide on standing
at room temperature for several days [22]. Heating of this
compound above its melting point or redistillation yielded
again pure trifluoroacetyl hydrazide. In our case, unlike the
referred example, heating displaced the equilibrium toward
the formation of the bridge compound 9. This phenome-
non, most likely, is determined by the entropic factor.
The possibility of transformation of tetrthiacalix[4]arene
2 into compound 9 was also confirmed by the next evi-
dence. The appearance of peak m/z = 977 [M+H]+ in the
MALDI-TOF mass spectra of 2 after long term storing,
heating or acidification of its solutions can be explained
by the presence of calix[4]arene 9 (M = 976). Moreover,
when we added one equivalent of hydrazine to the long
term stored solution 2, which 1H NMR spectrum contained
the additional signals, attributed to compound 9, the inten-
sities of these signals steeply decreased. This fact indicates
on the displacement of equilibrium from tetrathiaca-
lix[4]arene 9 to unbridged C4v symmetrical compound 2.
It is known that the disproportion of acetylhydrazide in
the presence of acetic acid [23], as well as, the disproportion
of formylhydrazide and acetylhydrazide in DMSO-d6 at
the addition of CF3COOH [22] leads to the formation of
corresponding N,N0-diacylhydrazine. We have also trans-
formed the hydrazide 1 to N,N0-diacylhydrazine 8 by the
heating of the former in HCl solution. When we added
the equimolar amount of CF3COOH to the solution of 2
the intensity of additional signals assigned to compound
9 sharply increased while the signals attributed to 2 disap-
peared (see Fig. 6). The character of spectrum changing
was the same as it was observed for that of compound 2,
Fig. 2. H-dimer in the crystal of 3. Only hydrogen atoms participated in
hydrogen bonding (dashed lines) are shown.
Fig. 5) in spectrum 2 appear in DMSO solution on heating.
The intensities of these peaks increase with increasing tem-
perature. On further cooling the intensities of signals
reduce, but they are not disappeared completely. It should
be noted that the same signals appear when DMSO solu-
tions of 2 were allowed to stand at room temperature for
several weeks. Similar changes were observed by us in the
spectrum of cone conformer of tetrahydrazide of ‘‘classi-
cal” calix[4]arene, which has endo-disposition of functional
groups similar to compound 2. However, for polyhydraz-
ides on the basis 1,3-alternate conformer of calix[4]phenol
(3), calix[4]resorcinol and calix[4]pyrogallol with exo-dis-
position of functional groups, as well as for model com-
pound 1 such phenomenon did not take place.
The formation of a bridge between two opposite frag-
ments in calixarene molecule (compound 9) is the most
probable explanation of this phenomenon. The process of
disproportionation of acetylhydrazide substituents evi-
dently occurs, during which the molecule of free hydrazine
is releasing:
Fig. 3. Fragment of the crystal packing in the crystal of compound 3. H-atoms not participated in the hydrogen bonding are omitted for clarity. Dashed
lines indicate the H-bonding. The view on the ac-plane.

V.V. Syakaev et al. / Journal of Molecular Structure 885 (2008) 111–121
117
constants related to trans-fragment of bridge have values
2JCðOÞ;CH = 3.9 Hz and 2JC(O),NH = 9.8 Hz, vicinal coupling
2
constant JOCH ;NH is not resolved (3J < 0.3 Hz). Geminal
3
2
proton–carbon coupling constant related to cis-fragment
of bridge is 2JCðOÞ;CH = 3.8 Hz, the constants 2JC(O),NH and
2
3JOCH ;NH are not observed (see Fig. 8). Meanwhile the sig-
2
nals of cis- and trans-conformers of ACH2AC(O)NHA
groups in N,N0-diacetylhydrazine bridge have equal intensi-
ties in 1H and 13C spectra. Thus, a cis/trans-conformation of
the N,N0-diacetylhydrazine bridge is realized for tetrathiaca-
lix[4]arene 9. This fact leads to the disruption of molecular
symmetry of this compound.
The asymmetry is appeared in spectrum of the frag-
ments which are connected with hydrazide substituents.
The protons of OACH2 groups are not equivalent
(d = 4.78 and 4.75 ppm) with geminal spin–spin coupling
constant 2J = 14.8 Hz. The nonequivalence of aromatic
protons is revealed in a less extent (d = 6.95 and 6.9 ppm,
4J = 1.3 Hz). The signals of aromatic and OACH2 protons
of the bridge fragment do not split. So, it can be concluded
that N,N0-diacetylhydrazine bridge links two opposite
phenoxy fragments in calix[4]arene. If the bridge was
formed between two neighboring phenoxy groups, the sym-
metry of all aromatic rings would be disturbed, which
would lead to their magnetic non-equivalence and as a
result to the splitting of aromatic proton signals in 1H
NMR spectra with coupling constants 4J ꢁ 1–3 Hz [24].
Such phenomenon has not been observed.
Hydrazide fragments in the molecule 9 have the trans-
configuration. Unfortunately, this assignment can be done
only by the considering of the chemical shifts, because the
spin–spin coupling constants of amide protons with carbon
atoms are not registrated in this case. This fact arises proba-
bly from the presence of the acid in the solution and is a result
of intensive proton exchange. The signals of OACH2 groups
Fig. 4. The circular intramolecular hydrogen bonds at lower rim of
tetrathiacalix[4]arene 2. Some atoms of calixarene are omitted for clarity.
under its heating. Probably, in both cases the disproportion
of one of acetylhydrazide groups and the subsequent for-
mation of N,N0-diacetylhydrazine bridge in molecule takes
place. Unfortunately, the signal 15N of free hydrazine
escaped detection in HSQC (15N) spectrum. It was appar-
ently caused by the fast spin–lattice relaxation of protons
and/or fast proton exchange in acid medium.
N,N0-Diacetylhydrazine fragment may be considered as
two amide groups connected by NAN bond. The hindered
rotation about C(O)AN bonds allows one to assume the
existence of four conformers (see Fig. 7). In 13C NMR spec-
trum of compound 9 the geminal proton–carbon coupling
Fig. 5. Influence of cyclic temperature change 303 K ? 383 K ? 303 K (from top to down) on 1H NMR spectra of 2 in the DMSO.

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V.V. Syakaev et al. / Journal of Molecular Structure 885 (2008) 111–121
Fig. 6. The 1H NMR spectra of 2 (DMSO-d6) in the presence of the equimolar amount of CF3COOH.
Fig. 7. Conformations of N,N0-diacetylhydrazine fragment.
of acetylhydrazide fragments are shifted to higher fields
the compound 6 mentioned above in [14]. In this
compound like as in compound 9 two opposite phenoxy
fragments are additionally connected by N,N0-diac-
etylhydrazine bridge. Unfortunately, we did not succeed
in preparing a crystal suitable for X-ray analysis. In this
connection for an unambiguous identification of the syn-
thesized compound structure we have used a combination
of methods 2D NMR spectroscopy.
The equal intensity of two groups of signals of the
bridge NH-protons indicates the cis/trans-conformation
of NHANH fragment in the molecule of 6, similar to the
observed for the compound 9.
1
(0.5 ppm in H NMR and 0.2 ppm in 13C NMR spectra)
compared with ones for 2. Signals of AC(O)A group in 13
C
spectra are shifted on 1 ppm lower than for initial tetrahyd-
razide 2. These changes are insignificant in comparison with
the difference between chemical shifts of cis- and trans-con-
formers in model hydrazones 4, 5 (13C: d(CH2trans) ꢀ
d(CH2cis) = 2 ppm and d(C(O)trans) ꢀ d(C(O)cis) = ꢀ4.5
ppm; 1H: d(CH2trans) ꢀ d(CH2cis) ꢄ ꢀ0.5).
The possibility of the transformation of compound 2
into compound 9 is proved by the fact that the condensa-
tion of hydrazides 2 with 4-nitrobenzaldehyde leads to

V.V. Syakaev et al. / Journal of Molecular Structure 885 (2008) 111–121
119
Fig. 8. The region of C(O) group signals in the 13C spectrum of compound
9 in DMSO-d6. The splitting of signals of carbonyl carbons: cis- (a), trans-
(b) amide groups in N,N0-diacetylhydrazine bridge.
The presence in the structure of calixarene 6 of two
hydrazone fragments, which can simultaneously exist as
geometrical isomers in respect to the C@N double bond
and as conformers about C(O)AN bond (see Fig. 9), leads
to the significant complication of the spectra of this com-
pound. The previously performed investigation of confor-
mational properties of model hydrazone 5 has showed
that only E-isomer around of C@N bond is realized in dif-
ferent solvents [12,13]. The spin–spin coupling constant
(1JC11,H11 = 163.4 Hz) of carbon C11 of hydrazone frag-
ments for compound 6 corresponds to EC@N isomer.
Three spatial forms of calix[4]arene with cis/cis-, trans/
trans- and cis/trans-amide conformations of hydrazone
fragments are realized in solution. This is demonstrated
by the fact that each group of NH signals of the bridge con-
sists of three peaks. It is also important that in subspectra
of corresponding spatial forms of calix[4]arene 6 the rela-
tive integral peak intensities in the groups remain equal
(see Fig. 10). The ratio of cis/trans hydrazone conformers
determined from NH-proton signals of the bridge is in
agreement with ratio obtained from intensities of CH2
group signals.
Fig. 10. The schema of assignment of C(O)NH signals of N,N0-
diacetylhydrazine fragment in the 1H spectrum of compound 6.
prevents the breaking of amide bond and facilitates the for-
mation of tetratiacalix[4]arene 7 bearing four acetylhydraz-
one groups.
The occurrence of four acetylhydrazone fragments in the
molecule of compound 7 leads to a large number of spatial
forms in the solution because of possible realization of four
conformational isomers for each fragment (see Fig. 11).
There are a lot of peaks in the NMR spectra of 7 in CDCl3
and DMSO-d6 solutions at 303 K, which makes the identi-
fication of the compound more difficult. It is also caused by
the presence of C(O), NH groups, pyridine nitrogen atoms
favorable to a large number of intra- and intermolecular
hydrogen bonds, which are remaining even in such polar
As mentioned above, under condensation of hydrazide 2
with pyridine-2-carboxaldehyde only the formation of tet-
rathiacalix[4]arene 7 functionalized by four acetylhydraz-
one fragments has been observed in contrary to the case
of 4-nitrobenzaldehyde [14]. The formation of intramolec-
ular hydrogen bond between nitrogen of pyridine ring
and NH group of neighboring acetylhydrazone fragment
or with NH group of the own fragment in ZC@N isomer
Fig. 9. Structures of the cis/trans-amide conformers and EC@N/ZC@N isomers of acetylhydrazone fragments.

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V.V. Syakaev et al. / Journal of Molecular Structure 885 (2008) 111–121
Table 3
Percentage of trans-amide conformer, coalescence temperatures and
values of the energy barrier of conformer’s conversion of hydrazones 4–7
Compound
trans (%)
Tc (K)
DG (kJ/mole)
DMSO
CDCl3
4a
5a
6
40
40
30
55
70
63
40
70
351
347
363b(373c)
350
68.8
67.9
70.5b(75.8c)
64.8
7
a
Ref. [13].
For acetylhydrazone fragments.
For N,N0-diacetylhydrazine bridge.
b
c
However, because of a bit small content of Z-isomer in
the equilibrium, the unambiguous identification from 13C
spectrum of 7 is impossible.
In our previous investigation it has been shown that the
irradiating a solution of compound 4 in CDCl3 by UV light
for half an hour in a quartz dish resulted in a 50% conver-
sion of the EC@N into the ZC@N isomer [13]. The irradiation
has not lead to any changes in spectrum of 7 in CDCl3
solution, i.e. the conversion of conformers in this case,
unlike to model compound 4, has not been observed.
The trans-conformer of investigated compounds (Table
3) can be stabilized in CDCl3 by intramolecular hydrogen
bonds of the NHꢃꢃꢃOCH2 groups, as observed by X-ray
analysis of calix[4]arene 3 and acetylhydrazone 5 in crystal
[12]. Apparently, this is the reason for increasing the per-
centage of cis-configuration of acetylhydrazone fragments
in DMSO, where the probability for the formation of
hydrogen bonds is low.
The energy barriers of the rotation around C(O)ANH
bond were determined by DNMR-experiments in
DMSO-d6. The DG values calculated for acetylhydrazone
fragments of tetrathiacalix[4]arenes 6, 7 slightly differ from
values obtained for model 4-tert-butylphenoxyacetylhyd-
razones 4 and 5 [13]. The largest energy barriers of cis/trans
conversion were found for C(O)ANH groups of N,N0-diac-
etylhydrazine bridge in the compound 6. This is caused by
the rigidity of additionally circle formed in the molecule
and the steric hindrance provided by the neighboring polar
acetylhydrazone groups.
Fig. 11. Influence of cyclic temperature change 303 K ? 383 K ? 303 K
(from top to down) on 1H NMR spectra of 7 in the DMSO-d6.
solvent as DMSO. Subspectra of different conformers are
overlapped, what hampered the determination of percent-
age of conformers. Under heating up to ꢁ350 K the peaks
coalescence and converge into sharp lines at 383 K (see
Fig. 11). Signals of carbonyl carbons at 172–170 ppm
(cis-conformer) and 167–165 ppm (trans-conformer) are
mostly well resolved (Table 2). The estimated ratio of cis/
trans-conformers is 45/55% in DMSO (Table 3).
4. Conclusions
The spin–spin coupling constant (1JC11,H11 = 163.4 Hz)
of carbon C11 of hydrazone fragments for compound 7
corresponds to EC@N isomer. Nevertheless, under heating
(383 K), when peaks of different conformers coalesce, a
main peak at 5.35 ppm and substantially less intensive
Characteristic spectral parameters, the conformation
and dynamic behaviour of tetrathiacalix[4]arenes function-
alized by hydrazide and hydrazone groups have been deter-
mined by means of NMR spectroscopy and X-ray analysis.
It was found that only trans-amide conformation of acety-
lhydrazide fragments of investigated tetrathiacalix[4]arenes
is realized.
The experimental results have showed that long term
storing, heating or acidification of solutions of cone con-
former of tetrathiacalix[4]arene functionalized by hydra-
zide groups in contrast to its 1,3-alternate analogues
1
one at 5.55 ppm are appeared in the H spectrum in the
region of CH2 group signals. The occurrence of that small
peak may be caused by the presence of some amounts of Z-
isomer. Whereas, the energy barrier of isomer’s conversion
is essentially higher than that for conformers, the proton
signals of isomers do not coalesce at this temperature.

V.V. Syakaev et al. / Journal of Molecular Structure 885 (2008) 111–121
121
leads to the formation of N,N0-diacetylhydrazine bridge in
molecule. This fact is the reason of the peculiarities of the
formation of acetylhydrazone derivatives of cone con-
former of calix[4]arene.
[6] Z. Asfary, V. Bo¨hmer, J. Harrowfield, J. Vicens (Eds.), Calixarenes
2001, Kluwer Academic Publishers, Dordrecht, 2001.
[7] 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, A.I. Konovalov, J. Incl. Phenomena 58 (2007) 55.
[8] R.I. Machkhoshvili, R.N. Shchelokov, Russ. J. Coord. Chem. 26
(2000) 677.
[9] S.N. Podyachev, S.N. Sudakova, V.V. Syakaev, A.K. Galiev, R.R.
Shagidullin, A.I. Konovalov, Supramol. Chem., Submitted for
publication.
The percentage of trans-conformation of acetylhydraz-
one groups of investigated compounds is higher in non-
polar CDCl3 than in DMSO. This conformation probably
is stabilized by intramolecular hydrogen bond NHꢃꢃꢃO
between amide hydrogen atom and oxygen atom of phen-
oxy group. The realization of large number of spatial forms
and intra- and intermolecular hydrogen bonds in the solu-
tion results in significant complication of NMR spectra of
compounds. Heating of solutions above coalescence tem-
perature leads to substantial simplification of spectra.
The largest energy barriers of cis/trans conversion were
found for C(O)ANH groups of N,N0-diacetylhydrazine
bridge in molecule 6.
[10] K. Andjelkovic, M. Sumar, I. Ivanovic-Burmazovic, J. Termal. Anal.
Calorim. 66 (2001) 759.
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Acknowledgement
This work is supported by the Russian Fund for Basic
Research (Grants 07-03-00325a and 05-03-32558a).
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