Synthesis and fluorescent properties of novel chiral 1,2-diaminocyclohexane substituted ligands and their complexes

Article abstract of DOI:10.1016/j.tet.2014.02.092

A series of novel chiral 1,2-diaminocyclohexane derivatives bearing heterocyclic units were synthesized via improved methods under ultrasonic irradiation. The photophysical properties of compounds were studied in ethanol, methanol, and chloroform. The sensitivity of these amines toward Cu ²⁺, Cd²⁺, and Ni²⁺ was studied by the UV-vis and fluorescent methods. The π-electron structure of thiophene and bithiophene containing sensors is the most active toward all above mentioned metal ions and is highly selective for Ni²⁺ and Cd²⁺.

Full text of DOI:10.1016/j.tet.2014.02.092

Accepted Manuscript
Synthesis and fluorescent properties of novel chiral 1,2-
diaminocyclohexanesubstituted ligands and their complexes
Violetta V. Meshkovaya, Alexander V. Yudashkin, Polina Y. Bushueva, Natalya B.
Eremeeva, Yuri N. Klimochkin
PII:
S0040-4020(14)00385-8
10.1016/j.tet.2014.02.092
TET 25391
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 21 October 2013
Revised Date: 19 January 2014
Accepted Date: 18 February 2014
Please cite this article as: Meshkovaya VV, Yudashkin AV, Bushueva PY, Eremeeva NB, Klimochkin
YN, Synthesis and fluorescent properties of novel chiral 1,2-diaminocyclohexanesubstituted ligands and
their complexes, Tetrahedron (2014), doi: 10.1016/j.tet.2014.02.092.
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ACCEPTED MANUSCRIPT
Synthesis and fluorescent properties of novel chiral 1,2-diaminocyclohexanesubstituted
ligands and their complexes
Violetta V. Meshkovaya*, Alexander V. Yudashkin, Polina Y. Bushueva, Natalya B.
Eremeeva, Yuri N. Klimochkin
Organic Chemistry Division, Samara State Technical University, Kuibyshev st. 153, 443010
Samara, Russia
Corresponding author. Tel./fax.: +7 846 332 21 22.
E-mail address: violetta.meshkovaya@yandex.ru (V.V. Meshkovaya)
Graphical abstract
Abstract
A series of novel chiral 1,2-diaminocyclohexane derivatives bearing heterocyclic units were
synthesized via improved methods under ultrasonic irradiation. The photophysical properties
of compounds were studied in ethanol, methanol and chloroform. The sensitivity of these
amines toward Cu2+, Cd2+ and Ni2+ was studied by the UV-Vis and fluorescent methods. The
π-electron structure of thiophene and bithiophene containing sensors is the most active toward
all above mentioned metal ions and is highly selective for Ni2+ and Cd2+.
Keywords
Fluorescent Chiral Ligand; Heterocyclic Schiff Base; UV/Vis Spectroscopy;
Diaminocyclohexane Ligand; Ultrasonic Activation
1. Introduction
Fluorescent compounds represent an important type of organic compounds due to their
properties and variety of applications with strong potential as photochromic azo dyes,
chromophores and in vitro fluorescent imaging probes for biodiagnosis.1-5 Push-pull
substituted heterocyclic compounds are of great interest due to their non-linear optical
properties which are useful for opto-electronic devices.6,7 Fluorophores based on a bithiophene
structure are used in excitation chirality method for determining the absolute configurations of
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chiral molecules on a microscale level and the recognition of chiral molecules.8,9 In recent
years, the research work of chemical sensors for ions began to develop rapidly and to replace
traditional analytical methods due to their advantages such as high sensitivity, selectivity and
detection simplicity.10 The chiral recognition method involves the application of chiral
structures with optical properties. The structure of non-racemic trans-1,2-diaminocyclohexane
satisfies requirements mentioned above. Thus new chiral sensors for ions and biomolecules
based on the 1,2-diaminocyclohexane moiety have become a fast-growing research field.8,11-14
Fluorescent receptors based on 1,2-diaminocylohexane with thiophene units indicate good
results for recognition of fluoride ions.15 Three decades ago, asymmetric reactions began to
play an important role in modern organic synthesis.16-18 The synthesis of new chiral ligands in
asymmetric reactions is the subject of ongoing scientific research.16-18 Complexes based on
chiral 1,2-diaminocyclohexane with aromatic fragments are widely used in some asymmetric
reactions: epoxidation of alkenes,19 asymmetric allylic alkylation,20 Henry reaction and
Michael addition.17,18,21 It has been shown that the properties of metal complexes depend on
the structure and metal-specific binding site of the ligand.22 The chiral unit of 1,2-
diaminocyclohexane has the most suitable geometry parameters and commercial availability
therefore it is the one of the important parts of the ligand structure.23,24 It is found that
thiophene containing ligands (I) have very good coordinating ability therefore vacant transition
metal orbitals and π-rich heteroatoms of the thiophene fragment are involved in complex
formation.18 Suitable catalysts, such as complexes of I Cu(II), have been found to greatly
increase enantioselectivity in the Henry reaction.18
High enantioselectivity and good yields made this research field ripe for further
exploration, and a series of thiophene containing ligands was synthesized.23,25 The best results
in allylic alkylation were obtained by using palladium complexes with two or three thiophene
23,26
units in the coordination sphere of the ligand structure
Synthesis, catalytic activity and
spectroscopic properties of thiophene, furan ligands and their derivatives, especially the nickel
complexes, have been insufficiently studied.21,27 In addition, the development of chiral ligands
allows them to be used as highly sensitive, selective and effective metal ion sensors and opens
a wide spectrum for their application.10,13
To research optical properties and the potential applications, a series of new
heterocyclic chiral structures based on 1,2-diaminocyclohexane were synthesized in this work.
The aim of this work was the synthesis of a series of heterocyclic ligands based on 1,2-
diaminocyclohexane as a chiral unit, and to study and compare optical properties of ligands
and their metal complexes.
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2. Results and discussion
2.1. Chemistry
In recent years several methods for the synthesis of chiral ligands based on 1,2-
diaminocyclohexane have been reported. One of the methods for azomethine synthesis from
the free (R,R)-1,2-diaminocyclohexane and aromatic aldehydes was carried out in
dichloromethane or ethanol as solvent at presence of anhydrous magnesium sulfate for 32 h at
ambient temperature.11,22,23,31-33 Significant improvement in some experiments was achieved
using of (R,R)-1,2-diammoniumcyclohexane mono-(+)-tartrate salt (DACHT) to avoid the use
of water-soluble air-sensitive free diamine in the reaction and the use of water-removing
11,23,28,29,32
reagents (MgSO4, Na2SO4, molecular sieves).
Thereby the reaction time was
decreased and the requirement to change reaction conditions depending on the aldehyde
structure was excluded.11,23,28,29,32 However, for isolation of free diamine from DACHT, base is
required.29 Condensation of aromatic aldehydes with DACHT at reflux in water-ethanol
mixture in presence of potassium carbonate produced azomethines with good yields.23,30 New
methods for reaction stimulation such as microwave and ultrasonic irradiation may facilitate
some reactions.24 The most studied heterocyclic diimines and their complexes are based on
thiophene-2-carbaldehyde, however, there is no data about thiophene-3-carbaldehyde and a
lack information about furan ligands, their complexes and spectroscopic properties.
It should be mentioned that carrying out the experiment under the described conditions30
with increase of the reaction temperature but without ultrasonic irradiation gives low yields
and side products. Ultrasonic irradiation of reaction media is a useful method for preparation a
series of azomethines (3a-3f) from corresponding aldehydes (2a-2f) and (R,R)-1,2-
diammoniumcyclohexane mono-(+)-tartrate salt (Scheme 1).
Scheme 1. Synthesis of diimines (2a-2f)
The use of ultrasonic irradiation for reaction activation allowed the reaction time to be
reduced to 1 h and the diimines to be isolated in good yields. However, the reaction time and
yield are seen to be greatly affected by the absence of ultrasonic irradiation. The most suitable
molar ratio of (R,R)-1,2-diammoniumcyclohexane mono-(+)-tartrate salt / aromatic aldehyde /
potassium carbonate is 1:2:2 respectively.
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Our interest is focused on the further reduction of the azomethines (2a-2f) to obtain new
heterocyclic ligands for complex formation with potential uses in asymmetric catalysis.
Reduction of the C=N bond in azomethines use NaBH4/methanol or NaBH4/THF with 10-fold
excess of NaBH4 and the reaction time varies up to 16 h at room temperature with good
yields11,22,23,29,34,35, but described reaction conditions lead to low yields of amines with
heterocyclic fragments. We found the reaction can be carried out in ethanol with NaBH4 with
reflux for 1 hour of the reaction mixture. The corresponding chiral amines (3a – 3f) were
obtained with high yields (>90%).
Scheme 2. Synthesis of amines (3a-3f)
The most suitable molar ratio of azomethine / NaBH4 is 1:2:2 respectively, and the
minimum volume of ethanol was used in the reaction.
2.2. Spectroscopic properties
The electronic spectra of compounds (3a-3f) were recorded in chloroform (10-3 M) and
showed an intense lowest energy charge-transfer absorption band in the UV-region (Table 1).
All compounds (3a-3f) exhibit an intense absorption in the UV-region and the position of this
band depends on the electronic nature of the heterocyclic ring and ring substituent.
Table 1. Yields, UV-Vis and fluorescent data of diamines (3a-3f) in chloroform (10-3
mole/l) and diamines 3a, 3c and 3e in ethanol (2*10-6 mole/l)
λem, nm (intensity,
Compound
Solvent
λabs, nm
νss (nm)
log ε
a.u.)
CHCl3
EtOH
253, 308
235
416 (135)
347 (142)
416 (141),
443 (132)
443 (120)
413 (72)
4.19, 3.54
4.95
108
112
3a
3b
CHCl3
252, 300
4.16, 3.36
143
CHCl3
EtOH
CHCl3
CHCl3
EtOH
CHCl3
247, 309
284
4.03, 3.55
4.86
134
129
106
70
3c
3d
3e
3f
248, 317
250, 355
307
423 (141)
425 (131)
375 (240)
423 (139)
4.20, 3.54
4.15, 3.74
4.91
68
249, 310
4.09, 3.83
113
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A slight bathochromic shift (8 nm) in the absorption spectrum in chloroform was
observed for structure 3a in comparison with 3b that proves greater interaction of the α-
substituent with thiophene π-system in 3a (Table 1). There is no significant effect on the
absorption maxima of the compound 3c with a furan moiety in comparison with 3a. At the
same time, there is a slight bathochromic shift (8 nm) for the methylfuran structure (3d). The
most considerable red-shift was observed for the 2,2′-bithiophene structure (3e) and, as with
compound 3f, it may suggest an interaction of the two π-electronic systems: thiophene and
olefin moieties. The absorption spectrum of 2,2′-bithiophene-containing structure (3e) shows
two main absorption bands in chloroform (Table 1). A broad band at ca. 355 nm may be
ascribed to an electron transfer transition and a band of moderate intensity at ca. 250 nm may
represent the π-π* local excitation transition of the heteroaromatic ring.
We measured the emission characteristics of compounds 3a-3f in chloroform. All the
emission spectra have a wide contour. In spite of the similar absorption maxima for 3a and 3b,
two fluorescence maxima were observed for 3-thienyl substituted 1,2-diaminocyclohexane
(3b). It is unexpected that the most significant bathochromic shift was noticed for the bis(2-
furfuryl)diaminocyclohexane (3c) but not for compound (3e). The furan ring in comparison
with thiophene has greater π-rich system that produces the red-shift of 3c (Table 1). At the
same time, the furan ring is less photostable than the thiophene unit and the fluorescence
intensity decreases over time for 3c. The nature of structure (3e) had an apparent influence on
the absorption and emission band of compound (3e). The wavelength maxima for absorption
and emission were shifted to longer wavelengths in the structure 3e due to the effective
interaction of the two thiophene units (Fig. 1, Table 1). The presence in structure 3f an
additional chromophore group (C=C) in the cyclic olefin moiety has a slight effect on the
absorption and emission maxima. The absorption and emission spectra of 3f are similar to the
corresponding spectra of 3a and 3b in chloroform (Table 1).
Fig. 1. Fluorescence emission spectra of compounds 3a – 3f in chloroform (3a λem =
416 nm; 3b λem = 416, 447 nm; 3c λem = 443 nm; 3d λem = 423 nm; 3e λem = 430 nm; 3f λem =
417 nm)
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A comparison of UV-Vis and emission spectra of 3a and 3e in ethanol suggests that
presence of two thiophene units in 3e facilitates bathochromic shift of the maxima in the
absorbance and fluorescence spectra (~70 nm) (Fig. 2, Table 1). The use of polar solvent leads
to increased red-shift of 3e in ethanol in contrast with chloroform that is completely consistent
with π* values by Kamlet et al.36 for solvents (Table 1).
The recognition properties of the compounds (3a, 3c, 3e) toward different metal ions:
Ni2+, Cd2+ and Cu2+ were studied by UV-Visible and fluorescence methods. The UV-spectra
and fluorescence spectra of initial ligands (3a, 3b, 3e) were recorded in ethanol (Table 1). The
UV-Vis spectrum of 3c measured in ethanol is similar to the spectrum measured in chloroform
and has a broad contour without intense maximum compared to the structures 3a and 3e with a
stable thiophene ring (Fig. 2). The UV-Vis spectra of complexes compounds (3a, 3c, 3e) with
cations have no change in either the wavelength values nor in the shapes of absorption spectra.
Fig. 2. UV-Vis spectra of compounds 3a, 3c, 3e in ethanol
The interaction 3a and 3e with Ni2+ was carried out at different molar ratio of ligand and
metal in ethanol-water and the intensity of fluorescence signal was measured over time. After
addition of Ni2+ to compound 3a at 2:1 molar ratio we observed the appearance of a new
fluorescence maxima at 408 nm within 30 s that can be attributed to complex formation and a
slight simultaneous increase in fluoresence intensity in contrast with the initial emission
spectrum (3a). Unexpected results were obtained at a 1:1 molar ratio of the compound 3a and
ion Ni2+ (Table 3). The appearance of a new intense fluorescent maxima in the longer
wavelength region (408 nm) was observed and at the same time quenching of initial emission
maximum (3a) (347 nm) during 5 min (Fig. 3) was observed. However the emission maxima
at 347 nm of compound 3a and new fluorescence signal of 3a-Ni2+ complex at 408 nm still
remain (Table 1, 2). It was possible to observe weak interactions between 3c and Ni2+ through
slight quenching of fluorescence maximum intensity and small bathocromic shift of emission
maximum (8 nm) (Table 2).
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Table 2. Fluorescence data of complexes with diamines (3a, 3c, 3e)a
λem,
nm
(Intensity,
a.u.)
λem,
nm
(Intensity,
a.u.)
λem,
nm
(Intensity,
a.u.)
Compound /
ion
Compound /
ion
Compound /
ion
3a / Ni2+
3c / Ni2+
3e / Ni2+
408 (29)
3a / Cd2+
3c / Cd2+
3e / Cd2+
349 (165)
3a / Cu2+
3c / Cu2+
3e / Cu2+
355 (190)
421 (57)
421 (54)
375 (75)
421 (57)
376 (109)
377 (166)
aThe measurement was carried out in ethanol-water 1:1 v/v (molar ratio 1:1 of
compound and metal ions (10-6M)).
Fig. 3. Fluorescence emission spectra of complex 3a and Ni2+ (at 1:1 molar ratio, ethanol-
water at 1:1 v/v within 5 min). The dark blue graph represents an initial emission spectrum of
3a
Similarly, we have studied interaction of 3e with Ni2+ but there is no notable change nor
in the absorption spectrum nor in the fluorescence spectrum intensity at 2:1 or 1:1 molar ratios
of ligand to ion. With an excess of Ni2+ a hypochromic effect and increase in the fluorescence
intensity of the main emission maximum were observed, also the second emission maximum
was found at approx. 448 nm (Fig. 4). Perhaps, the molecules of solvent may take part in the
external coordinating sphere at complex formation therefore red-shift is observed.
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Fig. 4. Emission spectra of complex 3e and Ni2+ (at 1:2 molar ratio in ethanol-water within 5
min).
The preparation of the nickel complex for enantioselective synthesis of γ-aminobutyric
acid derivatives from diethylmalonate and nitroalkenes was carried out in methanol as a
solvent.27 The interest for us is to study the spectroscopic parameters of compounds 3a and 3e
and their ability to form Ni(II) complexes with potential use as chemical sensors and catalysts
in asymmetric reactions. A series of experiments with compounds 3a and 3e was carried out in
methanol (Table 3). An aqueous solution of nickel (II) chloride was added to the methanol
solutions of 3a and 3e and emission spectra were recorded.
Тable 3. Fluorescence data of (3a, 3e) in methanol (10-3 mole/l)
λabs, nm
(intensity, а.u)
307 (3.56),
241 (3.82)
350 (3.99),
241 (3.51)
λex, nm
(intensity, а.u)
λem, nm
(intensity, а.u) l/mole•cm
ε,
νss, nm
Compound
342 (128)
384 (247)
423 (132)
440 (260)
141, 152 106, 172
607, 533 89, 198
3a
3e
Along with an increase π* values by Kamlet et al.36 for solvent polarity, a bathochromic
shift is observed in (3a) and (3e). Interaction of 3а with Ni2+ lead to the hypochromic effect
and hypsochromic shift of fluorescence maximum for one hour (Fig. 5), however the
appearance of a second maximum in contrast with interaction of 3a with Ni2+ in the ethanol-
water mixture was not observed (Fig. 3).
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Fig. 5. The hypochromic effect in emission spectra of 3a with Ni2+ in methanol (at molar ratio
ligand / ion 2:1 within 1 h)
After the addition of Ni2+ to the methanol solution of 3e a 9-fold increase in
fluorecsence intensity was observed (Fig. 6) and accompanied by a small bathochromic shift (5
nm).
Fig. 6. The increase of fluorescence intensity in emission spectra of 3e with Ni2+ in methanol
(at molar ratio ligand / ion 2:1 within 10 min)
We can assume the formation of the complex 3e with Ni2+ possibly facilitates the
formation of a more rigid, planar configuration of ligand 3e leading to the increase in
fluorescence intensity. On the other hand, methanol may possibly form an exiplex through the
compound’s outer coordination sphere.37
The decrease in fluorescence maxima and slight bathochromic shift (10 nm) were
observed for interaction of 3c with Cd2+ at 1:1 molar ratio in ethanol-water solution (Table 2).
Slight increase of the fluorescence intensity (on 16 per cent) was observed in the interaction of
ligand 3a with Cd2+ at 1:1 molar ratio in ethanol-water in comparison with initial emission
spectrum 3a (Table 1, 2). Unexpected results were obtained in the reaction of bithiophene
compound 3e with Cd2+ (1:1 molar ratio in ethanol-water). The significant decrease (3.2 times)
of new fluorescense maximum was observed within 30 min from the starting emission value
(375 nm, 134 a.u.) and to the final maximum (375 nm, 75 a.u.) (Fig. 7). The sensor 3e is
fluorescent in the absence of Cd2+, however, after binding 3e with Cd2+ an electron transfer
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from the fluorophore to the cation occurs. The mechanism of interaction 3e with Cd2+ is
photoinduced electron transfer (PET) and occurs upon complexation with a metal ion.38
Fig. 7. The emission spectra of complex 3e with Cd2+ (at molar ratio ligand / ion 1:1, water-
ethanol within 30 min)
Slight changes in the fluorescence intensity were observed for compound 3c with
copper ions in ethanol-water solution (Table 1, 2). The interaction 3a with Cu2+ in ethanol-
water had practically no effect on the wavelength maxima of absorption and emission spectra.
The significant decrease in intensity (in 1.5 times) of fluorescenсe maximum was observed in
emission spectrum of compound 3e with Cu2+. Perhaps, the fluorescence signal of 3e is
quenched by the Cu2+ ion due to the formation of a stable complex.39 A strong decrease of the
fluorescence intensity is suggested to a chelation enhanced quenching (CHEQ effect)40 during
complex formation 3e with Cu2+. Therefore the chelated amine electron lone pairs become
involved in bonding with the metal ion and they are unable to donate an electron to the excited
molecule. In addition we may suggest that a short spacer such as methylene group between the
bithiophene and diaminocyclohexane may be suitable for effective energy transfer.
3. Conclusions
A series of novel chiral compounds (3a-3f) was synthesized in modified conditions under
ultrasonic irradiation, and these new ligands have a great potential as chemosensors and
catalysts for asymmetric reactions in the near future. The results showed the equal sensory
ability of compound 3c for Ni2+, Cd2+ and Cu2+ in ethanol-water solution. The ligand 3a has
medium sensory ability toward Cu2+ and slight change in interaction with Cd2+ ion in ethanol-
water. It was found that the interaction of compound 3a with Ni2+ in ethanol-water solution
leads to the formation of two maxima in its emission spectrum that may be referred to
equilibrium of ligand and complex. The bithiophene unit 3e leads to stronger sensitivity that
demonstrates as for Cu2+ and so for Cd2+ where we observed the quenching of fluorescent
signal, especially for Cd2+. Moreover, unexpected results had been found for complex 3e with
Ni2+ ion in methanol, so there instead of fluorescence quenching we observed a significant
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increase in the emission intensity of fluorescence spectrum. The possible explanation of
different sensitivity of metal ions toward ligand 3e may be referred to the ion size or to the
greater fluorescence quenching effect due to the d-orbitals of Cd2+ and Cu2+.41,42 Besides that
the concentration of compounds are in the 10-4 – 10-6 mol/l range that allowed to carry out the
analysis at very low ligand concentration in the water-alcohol solutions.
Thereby we can assume that the series of synthesized compounds holds promise as
useful chemosensors for a variety of ions in the near future, and furthermore these compounds
may be used as ligands in complexes for the catalysis of asymmetric reactions, for example,
Henry reaction and Michael addition.
4. Experimental
4.1 General information and materials
Experiments with air and moisture sensitive materials were carried out under argon
atmosphere. Glassware was oven dried for several hours. Silica gel 60, Merck 230-400 mesh,
was used for preparative column chromatography. Reagents were commercially available from
Sigma Aldrich, Merck and were used without further purification. FTIR spectra were taken on
a Shimadzu IRAffinity-1 spectrophotometer in KBr pellets or thin-layer (KBr prisms). NMR
spectra were recorded on a JEOL JNM ECX 400MHz spectrometer in DMSO-d6 and CDCl3
using tetramethylsilane (TMS) as an internal reference. Chemical shifts and coupling constants
were recorded in units of ppm and Hz, respectively. Melting points were determined on an
electrothermal melting point apparatus and are uncorrected. Elemental analysis was performed
on a EuroVector EA-3000 instrument. Electron impact–mass spectrometry (EI-MS) spectra
were obtained on a Finnigan Trace DSQ spectrometer (70 eV). Analytical thin-layer
chromatography (TLC) was performed on aluminum-backed silica-gel plates (Merck 60 F254
and Marchery Nagel). Visualization of components was accomplished with ultraviolet light
(365 nm) or exposure to I2. Optical rotations were measured on Rudolph Research Analytical
(Autopol V Plus Automatic Polarimeter) with a sodium lamp at different wavelengths (436,
589, 633 nm) at 1 cm cell and are reported as follows: [α]D20°C (c = g/100 ml, solvent).
Chloroform, ethanol and methanol were employed as solvents for absorption and
fluorescence measurements prepared according to described methods.43 UV/Vis absorption
spectra were recorded on a Shimadzu UV mini-1240 spectrophotometer in a 1 cm quartz cell,
in comparison to solvent blank, at the wavelength range 200-550 nm. Emission spectra were
obtained on a Cary Eclipse Varian Fluorescence Spectrophotometer in a 1 cm quartz cell at the
wavelength range 200 – 650 nm, excitation and emission slits are 5 nm. The excitation
wavelength was at the maxima of excitation spectra. The emission spectra were recorded at
right angle relative to the cell. Solutions of the amines (3a-3f) (ca. 10-5 - 10-6 M) and of the
cations under study (ca. 10-5 - 10-6 M) were prepared in ethanol or in mixtures of ethanol-water
equal to the molar ratios in the form of NiCl2•6H2O, Cd(CH3COO)2•6H2O,
Cu(CH3COO)2•H2O. Titration of the compounds with the cations was performed by the
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sequential addition of the equivalents of cation in the solution to the amine solution, in a 10
mm path length quartz cuvette and emission spectra were measured by excitation at the
wavelength of maximum absorption for each compound over time (varies from 5 to 60 min).
The addition of metal ion solution in water to the ligand ethanol solution were made in the 3
different ratios: 1 molar equivalent of metal ion solution / 2 molar equivalents of ligand
solution, 1 molar equivalent of metal ion solution / 1 molar equivalent of ligand solution, 2
molar equivalents of metal ion solution / 1 molar equivalent of ligand solution. The
concentration of the samples in methanol and chloroform was in a range 2×10-3 - 25×10-3
0
mol/l, measurements were carried out at 25 С over time (varies from 1 to 60 min). The
aqueous solution of NiCl2•6H2O was added to the ligand in methanol at the ratio 1 molar
equivalent of metal ion / 2 molar equivalents of ligand solution.
4.2. Synthesis of the compounds
4.2.1 Synthesis of initial compounds
2,2′-Bithiophene was prepared by improved Ulmann method,44 yield 70%, bp 102-108
°С/4 Torr.44 Synthesis of 2-(4′-methylcyclohex-1′-en-1′-yl)thiophene was carried out by the
Grignard reaction, yield 77%. 2,2′-Bithiophene-5-carbaldehyde (1e) was prepared by the
described procedure,45 yield 75%. Synthesis of 5-(4′-methylcyclohex-1′-en-1′-yl)thiophene-2-
carbaldehyde (1f) was carried out by the Vilsmeier-Haack method, yield 79%. Diastereomeric
pure (1R,2R)-(-)-1,2-diaminocyclohexane mono-(+)-tartrate (8) was obtained from the mixture
of trans-1,2-diaminocyclohexanes by the described method;28 mp 274-276°С28.
4.2.2 General procedure for azomethine synthesis (2a-2f)
Saturated K2CO3 solution (0.02 mol) and (1R,2R)-(-)-1,2-diaminocyclohexane mono-
(+)-tartrate (0.01 mole) were dispersed under ultrasonic irradiation for 5 min. The
corresponding aldehyde (1a-f) (0.02 mol) was dissolved in 20 ml of ethanol and added
dropwise to the reaction mixture. The reaction was carried out under ultrasonic irradiation for
1 h at 40-45°С. The resulting precipitate was filtered off, washed twice with distilled water and
ethanol. If necessary, the azomethine (2a-2f) was crystallized from ethanol.
4.2.2.1 (1R,2R)-N,N'-bis[(E/Z)-thiophen-2-ylmethylidene]cyclohexane-1,2-diamine (2a). Yield
90%; mp 128-133°С. IR (KBr), cm–1: 2926, 2843, 1635, 1431, 1219, 1083, 935, 854, 743, 709.
1
3
Н NMR (CDCl3); δ ppm: 8.25 (s, 2Н, N=CH), 7.27 (dd, 2Н, J 5.0 Hz, 4J 1.1 Hz, 5-Н), 7.12
(dd, 2Н, 3J 3.7 Hz, 4J 1.1 Hz, 3-Н), 6.94 (dd, 2H, 3J 3.7 Hz, 3J 5.0 Hz, 4-Н), 3.27-3.35 (m, 2H,
tert-СН), 1.72-1.84 (m, 6H, СН), 1.40-1.46 (m, 2H, СН). C NMR (CDCl3); δ ppm: 154.4,
13
142.6, 130.3, 128.3, 127.3, 73.5, 32.9, 31.0, 24.5. Anal. Calcd. for C16H18N2S2: C, 63.54; H,
6.00; N, 9.26; S, 21.20. Found: C, 63.50; H, 6.07; N, 9.21; S, 21.26.
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4.2.2.2. (1R,2R)-N,N'-bis[(E/Z)-thiophen-3-ylmethylidene]cyclohexane-1,2-diamine (2b).
Yield 94%, mp 128-132°С. IR (KBr), cm–1: 2927, 2854, 1639, 1240, 1078, 937, 866, 800, 783.
1
4
Н NMR (CDCl3); δ ppm: 8.18 (s, 2Н, N=CH), 7.42 (dd, 2H, 4J 1.2 Hz, J 2.9 Hz, 2-Н), 7.39
(dd, 2Н, 3J 5.1 Hz, 4J 1.2 Hz, 5-Н), 7.21 (dd, 2Н, 3J 5.1 Hz, 4J 1.2 Hz, 4-Н), 3.26-3.33 (m, 2H,
tert-СН), 1.70-1.84 (m, 6H, СН), 1.44-1.51 (m, 2H, СН). C NMR (CDCl3); δ ppm: 155.5,
13
140.7, 130.0, 126.1, 125.9, 73.9, 33.1, 24.6. Anal. Calcd. for C16H18N2S2: C, 63.54; H, 6.00; N,
9.26; S, 21.20. Found: C, 63.58; H, 6.06; N, 9.27; S, 21.12.
4.2.2.3. (1R,2R)-N,N'-bis[(E/Z)-furan-2-ylmethylidene]cyclohexane-1,2-diamine (2c). Yield
85%. IR (KBr), cm–1: 2931, 2858, 1647, 1485, 1068, 1014, 933, 767, 740. 1Н NMR (CDCl3); δ
ppm: 7.99 (s, 2Н, N=CH), 7.41 (2Н, d, 3J 1.8 Hz, 5-Н), 6.55 (d, 2H, 3J 3.4 Hz, 3-Н), 6.36 (dd,
3
3
2H, J 3.4 Hz, J 1.8 Hz, 4-Н), 3.31-3.35 (m, 2H, tert-СН), 1.75-1.83 (m, 6H, СН), 1.40-1.43
13
(m, 2H, СН). C NMR (CDCl3); δ ppm: 151.4, 149.6, 144.5, 114.4, 111.5, 74.1, 33.1, 24.5.
Anal. Calcd. for C16H18N2O2: C, 71.09; H, 6.71; N, 10.36. Found: C, 71.15; H, 6.78; N, 10.40.
4.2.2.4.
(1R,2R)-N,N'-bis[(E/Z)-(5-methylfuran-2-yl)methylidene]cyclohexane-1,2-diamine
1
(2d). Yield 97%. IR (KBr), cm–1: 2927, 2858, 1643, 1535, 1022, 929, 786. Н NMR (CDCl3);
3
3
δ ppm: 7.84 (s, 2Н, N=CH), 6.37 (d, 2Н, J 3.2 Hz, 3-Н), 5.90 (d, 2H, J 3.2 Hz, 4-Н), 3.23-
3.30 (m, 2H, tert-СН), 2.23 (s, 6H, 2×СН3), 1.68-1.74 (m, 6H, СН), 1.30-1.39 (m, 2H, СН).
13C NMR (CDCl3); δ ppm: 155.3, 150.1, 149.5, 116.3, 107.9, 74.1, 43.5, 33.2, 24.5, 14.0.
Anal. Calcd. for C18H22N2O2: C, 72.46; H, 7.43; N 9.39. Found: C, 72.45; H, 7.41; N, 9.41.
4.2.2.5. (1R,2R)-N,N'-bis[(E/Z)-(2,2′-bithiophene-5-yl)methylidene]cyclohexane-1,2-diamine
(2e). Yield 91%, mp 110-113°С. IR (KBr), cm–1: 2935, 2843, 1624, 1462, 1226, 1087, 835,
1
3
4
790, 696, 686. Н NMR (CDCl3); δ ppm: 8.20 (s, 2Н, N=CH), 7.20 (dd, 2Н, J 5.2 Hz, J 1.2
Hz, 5-Н), 7.18 (dd, 2Н, 3J 3.7 Hz, 4J 1.2 Hz, 4-Н), 7.00-7.04 (m, 4H, 3-Н, 3′-Н), 6.99 (dd, 2H,
3J 3.7 Hz, 3J 5.2 Hz, 4′-Н), 3.25-3.32 (m, 2Н, tert-СН), 1.72-1.87 (m, 6H, СН), 1.40-1.46 (m,
13
2Н, СН). C NMR (CDCl3); δ ppm: 154.3, 141.0, 140.0, 137.3, 131.1, 128.0, 125.2, 124.5,
123.6, 73.5, 32.9, 24.5. Anal. Calcd. for C24H22N2S4: C, 61.76; H, 4.76; N, 6.00; S, 27.48.
Found: C, 61.78; H, 4.74; N, 6.02; S, 27.46.
4.2.2.6.
(1R,2R)-N,N'-bis[(E/Z)-(5-(4-methylcyclohex-1-ene-1-yl)thiophene-2-
yl)methylidene]cyclohexane-1,2-diamine (2f). Yield 60%, mp 147-149°С. IR (KBr), cm–1:
1
2924, 2858, 1627, 1460, 1226, 792. Н NMR (CDCl3); δ ppm: 8.15 (s, 2Н, N=CH), 6.98 (d,
2Н, 3J 3.7 Hz, 4-Н), 6.79 (d, 2Н, 3J 3.7 Hz, 3-Н), 6.19 (br, 2H, С=СН), 3.24-3.28 (m, 2H, tert-
3
СН), 2.20-2.46 (m, 6H, СН), 1.55-1.81 (m, 10H, СН), 1.21-1.40 (m, 4H, CH), 0.97 (d, 6H, J
13
6.4 Hz, 2×СН3). C NMR (CDCl3); δ ppm: 154.6, 149.4, 139.4, 130.9, 130.8, 125.4, 121.4,
73.5, 34.4, 33.0, 30.9, 28.1, 27.3, 24.5, 21.7. Anal. Calcd. for C30H38N2S2: C, 73.42; H, 7.85;
N, 5.71; S, 13.07. Found: C, 73.40; H, 7.81; N, 5.72; S, 13.07.
13

ACCEPTED MANUSCRIPT
4.2.3 General procedure of amines synthesis (3a-3f)
The corresponding azomethine (0.01 mol) is dissolved in the minimal volume of
ethanol. NaBH4 (0.1 mol) was added with intensive stirring at room temperature and then the
mixture refluxed for 1 h. The reaction mixture is cooled to r.t. and half of the ethanol was
evaporated, the residue is poured into cold water. The amine is extracted with methylene
chloride (3×50 ml), dried over anhydrous MgSO4. Solvent was removed with a rotary
evaporator and the amines were obtained with good yields.
4.2.3.1. (1R,2R)-N,N'-bis(thiophen-2-ylmethyl)cyclohexane-1,2-diamine (3a). Yield 98%, mp
70-72°С. [α]D20 -76.8 (с 0.05, CHCl3). IR (KBr), сm–1: 3298, 2924, 2850, 1450, 1111, 694. 1Н
3
NMR (CDCl3); δ ppm: 7.18 (dd, 2H, J 5.0 Hz, 4J 1.4 Hz, 5-H), 6.90-6.94 (m, 4H, 3-H, 4-H),
4.1 (d, 2H, J 14.2 Hz, CH-NH), 3.88 (d, 2H, J 14.2 Hz, CH-NH), 2.26-2.30 (m, 2H), 2.05-2.15
(m, 2H), 1.70-1.74 (m, 2H), 1.20-1.25 (m, 2H), 1.01-1.05 (m, 2H). 13C NMR (CDCl3); δ ppm:
145.2, 126.6, 124.5, 124.3, 60.5, 45.6, 31.6, 25.1. Anal. Calcd. for C16H22N2S2: С, 62.70, H,
7.24, N, 9.14, S, 20.92. Found: С, 62.73; H, 7.22; N, 9.15; S, 20.90.
4.2.3.2. (1R,2R)-N,N'-bis(thiophen-3-ylmethyl)cyclohexane-1,2-diamine (3b). Yield 86%, mp
70-72°С. [α]D -76.3 (с 0.05, CHCl3). IR (KBr), сm–1: 3294, 2924, 2850, 1450, 1111, 856,
20
833, 770. 1Н NMR (CDCl3); δ ppm: 7.25 (d, 2H, 3J 5.0 Hz, 5-H), 7.08-7.11 (m, 2H, 2-H), 7.04
(d, 2H, 4-H), 3.91 (d, 2H, J 13.9 Hz, CH-NH), 3.68 (d, 2H, J 13.9 Hz, CH-NH), 2.22-2.27 (m,
13
2H), 2.04-2.15 (m, 2H), 1.65-1.74 (m, 2H), 1.19-1.25 (m, 2H), 1.00-1.10 (m, 2H). C NMR
(CDCl3); δ ppm: 142.1, 127.7, 125.8, 121.2, 60.9, 46.0, 31.6, 25.1. Anal. Calcd. for
C16H22N2S2: С, 62.70; H, 7.24; N, 9.14; S, 20.92. Found: С, 62.68; H, 7.17; N, 9.10; S, 20.85.
20
4.2.3.3. (1R,2R)-N,N'-bis(furan-2-ylmethyl)cyclohexane-1,2-diamine (3c). Yield 83%, [α]D
-
42.5 (с 0.05, CHCl3). IR (KBr), cm–1: 3302, 2924, 2854, 1450, 1149, 1010, 732. Н NMR
(CDCl3); δ ppm: 7.20-7.22 (dd, 2H, 3J 3.4 Hz, 4J 1.8 Hz, 5-H), 6.16-6.17 (d, 2H, 4J 3.4 Hz, 3-
H), 6.07-6.08 (dd, 2H, 4J 1.8 Hz, 3J 3.4 Hz, 4-H), 3.75 (d, 2H, CH-NH), 3.61 (d, 2H, CH-NH),
2.10-2.18 (m, 2H), 1.90-1.94 (m, 2H), 1.56-1.64 (m, 2H), 1.05-1.11 (m, 2H), 0.90-1.00 (m,
2H). 13C NMR (CDCl3); δ ppm: 154.0, 141.6, 110.2, 106.8, 60.4, 43.3, 31.1, 24.9. Anal. Calcd.
for C16H22N2O2: С, 70.04; H, 8.08; N, 10.21. Found: С, 70.08; H, 8.11; N, 10.15.
1
4.2.3.4. (1R,2R)-N,N'-bis[(5-methylfuran-2-yl)methyl]cyclohexane-1,2-diamine (3d). Yield
94%, [α]D20 -52.0 (с 0.05, CHCl3). IR (KBr), сm–1: 3302, 2924, 2855, 1566, 1450, 1219, 1114,
1018, 783. 1Н NMR (CDCl3); δ ppm: 5.95 (d, 2H, 3J 3.2 Hz, 3-Н), 5.77 (d, 2Н, 3J 3.2 Hz, 4-Н),
3.70 (d, 2Н, J 14.2 Hz, CH-NH), 3.54 (d, 2Н, J 14.2 Hz, CH-NH), 2.14 (s, 6H, 2×СН3), 1.93-
13
2.00 (m, 2H), 1.60-1.65 (m, 4H), 1.10-1.20 (m, 2H), 0.90-0.98 (m, 2H). C NMR (CDCl3); δ
ppm: 152.8, 151.0, 107.1, 106.0, 60.6, 43.7, 31.5, 25.1, 13.6. Anal. Calcd. for C18H26N2O2: С,
71.49; H, 8.67; N, 9.26. Found: С, 71.55; H, 8.71; N, 9.25.
14

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4.2.3.5. (1R,2R)-N,N'-bis[(2,2′-bithiophene-5-yl)methyl]cyclohexane-1,2-diamine (3e). Yield
88%, [α]D -9.2 (с 0.01, CHCl3). IR (KBr), сm–1: 3290, 2920, 2850, 1458, 1099, 833, 798,
20
1
3
4
3
698. Н NMR (CDCl3); δ ppm: 7.15 (dd, 2Н, J 5.0 Hz, J 1.4 Hz, 5′-Н), 7.08 (dd, 2Н, J 3.7
4
3
3
3
Hz, J 1.4 Hz, 3′-Н), 6.98 (d, 2H, J 3.6 Hz, 4-Н), 6.94 (dd, 2Н, J 5.0 Hz, J 3.7 Hz, 3′-Н),
3
3
3
6.81 (d, 2H, J 3.6 Hz, 3-Н), 4.07 (d, 2Н, J 14.1 Hz, CH-NH), 3.86 (d, 2Н, J 14.1 Hz, CH-
NH), 2.34-2.38 (m, 2H), 2.10-2.16 (m, 2H), 1.71-1.75 (m, 2H), 1.20-1.26 (m, 2H), 1.02-1.08
13
(m, 2H). C NMR (CDCl3); δ ppm: 144.4, 137.9, 136.3, 127.8, 125.2, 124.0, 123.4, 123.3,
60.5, 45.7, 31.5, 29.8, 25.0. Anal. Calcd. for C24H26N2S4: С, 61.22; H, 5.57; N, 5.95; S, 27.25.
Found: С, 61.16; H, 5.50; N, 5.97; S, 27.29.
4.2.3.6.
(1R,2R)-N,N'-bis[(5-(4-methylcyclohex-1-ene-1-yl)thiophene-2-
20
yl)methyl]cyclohexane-1,2-diamine (3f). Yield 91%, [α]D -5.0 (с 0.01, CHCl3). IR (KBr),
сm–1: 3290, 2924, 2862, 1624, 1454, 1357, 1111, 1022, 787. Н NMR (CDCl3); δ ppm: 6.69-
1
6.76 (m, 4Н, 3-Н, 4-Н), 6.06 (br s, 2Н), 4.02 (d, 2Н, 3J 14.2 Hz, CH-NH), 3.80 (d, 2Н, 3J 14.2
3
Hz, CH-NH), 2.05-2.50 (m, 12H), 1.62-1.85 (m, 8H), 1.15-1.33 (m, 6H), 0.97 (d, 6H, J 4.3
Hz, 2×СН3). C NMR (CDCl3); δ ppm: 145.7, 142.0, 131.0, 124.8, 123.1, 120.7, 60.2, 45.7,
13
34.3, 31.4, 31.0, 28.3, 27.3, 25.0, 21.8. Anal. Calcd. for C30H42N2S2: С, 72.82; H, 8.56; N,
5.66; S, 12.96. Found: С, 72.75; H, 8.64; N, 5.70; S, 12.97.
Acknowledgements
This work was financially supported by the Russian Ministry of Education and Science
within basic part of government assignment for scientific research with use of equipment of
Multiple-Access Center “Investigation of the physicochemical properties of substances and
materials” of Samara State Technical University.
Supplementary data
Supplementary data associated with this article can be found, in the online version, at
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Supplementary data
Cu, 5 h
180-190 oC
DMF, POCl3
CHO
I
S
S
1,2-dichloro-
ethane
S
S
S
1e
4
Mg, Et2O
O
CH3
1)
DMF, POCl3
MgI
CH3
H3C
S
CHO
1,2-dichloro-
ethane
S
S
2) NH4Cl (aq)
5
1f
2,2′-Bithiophene (4) was prepared by improved Ulmann method1: a mixture of 2-
iodothiophene (82 g, 0.39 mole) and copper (50 g, 0.78 mole) was refluxed (180 - 190°С)
with stirring for 3 hours. The reaction mixture was extracted with 1,2-dichloroethane
(3×200 ml) and copper iodide was removed by filtration. The solvent was removed with a
rotary evaporator, the fractional distillation of the residue gave the title compound 4 (22.7
g, 70%); bp 102-108 °С/4 Torr)1.
Synthesis of 2-(4′-methylcyclohex-1′-en-1′-yl)thiophene (5)
A solution of 2-iodothiophene (35.7 g, 0.17 mole) in dry Et2O (85 ml) was added
dropwise from a dropping funnel to a magnesium turnings (4.34 g, 0.18 mole) in dry
Et2O (10 ml). The reaction mixture was heated on the water bath for 2.5 h (until
magnesium turnings disappeared). The Grignard reagent was cooled to 0-5 °С and 4-
methylcyclohexanone (14.1 g, 0.125 mole) in dry Et2O (30 ml) was added dropwise
from a dropping funnel. After ketone addition, the reaction mixture was heated for 1 h on
the water bath. The solution was cooled to 0 °C and the mixture was quenched with
dilute NH4Cl solution. The ether phase was separated, washed with water and dried over
anhydrous MgSO4. After filtration, solvent was removed with a rotary evaporator. The
crude product mixture was fractionally distilled to obtain desired compound 5 (17.13 g,
77%) as slight yellow liquid; bp 107-112°С/5-7 Torr. IR (KBr), cm–1: 2947, 2920, 2870,
1
3
1454, 1434, 1234, 844, 802, 690. Н NMR (DMSO-d6); δ ppm: 7.23 (dd, 1H, J 4.1 Hz,
4J 2.0 Hz, 5-Н), 6.92 (dd, 2Н, J 4.1 Hz, J 2.0 Hz, 3-Н, 4-Н), 6.05 (br, 1H, СН), 2.38-
2.43 (m, 1H, СН), 2.25-2.34 (m, 1H, СН2), 2.13-2.21 (m, 1H, СН2), 1.56-1.75 (m, 3H,
СН2), 1.19-1.29 (m, 1H, tert-CH), 0.91 (d, 3H, 3J 6.4 Hz, СН3). 13C NMR (DMSO-d6); δ
ppm: 146.3, 131.0, 127.8, 123.7, 123.3, 122.0. Anal. Calcd. for C11H14S: C, 74.10; H,
7.91; S, 17.98. Found C, 74.23; H, 8.01; S, 18.06.
3
4
Synthesis of 2,2′-bithiophene-5-carbaldehyde (1e)
2,2′-Bithiophene-5-carbaldehyde (1e) was prepared by the improved procedure.2
To the mixture of 2,2′-bithiophene (4) (44 g, 0.027 mol) and N,N-dimethylformamide
(3.9 g, 0.053 mol) in 1,2-dichloroethane (44 ml) was added dropwise from a dropping
funnel POCl3 (6.3 g, 0.042 mol) at 0-5 °С. Reaction mixture was stirred for 5 h at room
temperature. The mixture was quenched with saturated NaHCO3 solution (pH = 7-8).
Organic phase was separated, washed several times with water, and dried over

ACCEPTED MANUSCRIPT
anhydrous MgSO4. Solvent was removed with a rotary evaporator and the residue
crystallized from n-hexane. Yield 3.9 g (75%); mp 52-55 °С.2
Synthesis of 5-(4′-methylcyclohex-1′-en-1′-yl)thiophene-2-carbaldehyde (1f)
The Vilsmeier-Haack reagent was prepared to avoid side reactions and to increase
yield of compound (5). POCl3 (7 ml, 0.075 mol) was added dropwise from a dropping
funnel at 5-10 °С to the stirring N,N-dimethylformamide (9.67 g, 0.125 mol). To the
mixture of compound (5) (8.9 g, 0.05 mol) in of 1,2-dichloroethane (30 ml) Vilsmeier-
Haack reagent was added dropwise at 10-15 °С. The reaction mixture was allowed to
warm up and kept for 10 h at room temperature. The mixture was poured into crushed
ice and then neutralized with NaHCO3. The aqueous layer was extracted with 1,2-
dichloroethane and dried over anhydrous MgSO4. The solvent was removed with a rotary
evaporator, the resulting precipitate filtered off and washed with n-hexane to afford the
pure compound 7 (7.8 g, 79%) as pale yellow needles; mp 76-78 °С. IR (KBr), cm–1:
1
2924, 2854, 1651, 1454, 1226, 1033, 794, 671. Н NMR (DMSO-d6); δ ppm: 9.80 (s,
1Н, СНО), 7.61 (d, 1Н, 3J 3.9 Hz, 4-Н), 7.03 (d, 1Н, 3J 3.9 Hz, 3-Н), 6.40 (br, 1H, СН),
2.40-2.50 (m, 2H, СН), 2.25-2.34 (m, 1H, СН), 1.79-1.88 (m, 2H, СН), 1.68-1.77 (m,
3
13
1H, СН), 1.31-1.41 (m, 1H, tert-CH), 0.99 (d, 3H, J 6.4 Hz, СН3). C NMR (DMSO-
d6); δ ppm: 182.9, 157.0, 140.5, 137.3, 130.7, 128.6, 122.3, 34.4, 30.7, 28.0, 27.4, 21.6.
MS (EI) m/z (%): M+ 206 (100), [M+ -CH3] 191 (30), [M+ -CHО] 177 (50). Anal. Calcd.
for C12H14OS: C, 69.86; H, 6.84; S, 15.54. Found: C, 69.97; H, 6.80; S, 15.61.
References and notes
1. Wynberg, H.; Logothetis, A. J. Am. Chem. Soc. 1956, 58, 1958-1961.
2. Wei, Y.; Wang, B.; Wang, W.; Tian, J. Tetrahedron Lett. 1995, 36, 665-668.