4-Alkoxycarbonyl-2-(2-pyridyl)thiazoles and their complexes with CuII and CoII. Molecular and crystal structure of copper 4-ethoxycarbonyl-2-(2-pyridyl) thiazole dichloride

Article abstract of DOI:10.1007/s11172-009-0104-5

The first synthesis of ethyl 2-(2-pyridyl)thiazole-4-carboxylate (2) and bis[2-(2-pyridylthi-azol-4-ylcarbonyloxy)ethyl] disulfide (4) is described. The complexation of compounds 2 and 4 with CuII, CoII, and NiII chlorides and perchlorates has been studied. Electrochemical behavior of the ligands and complexes obtained has been investigated by cyclic voltammetry and using rotating disk electrode, which allowed us to confirm the possibility for the ligand 4 and its complexes to be adsorbed on the surface of a gold electrode.

Full text of DOI:10.1007/s11172-009-0104-5

Russian Chemical Bulletin, International Edition, Vol. 58, No. 4, pp. 844—850, April, 2009
844
4ꢀAlkoxycarbonylꢀ2ꢀ(2ꢀpyridyl)thiazoles and their complexes
with CuII and CoII. Molecular and crystal structure
of copper 4ꢀethoxycarbonylꢀ2ꢀ(2ꢀpyridyl)thiazole dichloride
A. G. Majouga, E. K. Beloglazkina, V. V. Frolov, A. A. Moiseeva, and N. V. Zyk
Department of Chemistry, M. V. Lomonosov Moscow State University,
1 Leninskie Gory, 119992 Moscow, Russian Federation.
Eꢀmail: bel@org.chem.msu.ru
The first synthesis of ethyl 2ꢀ(2ꢀpyridyl)thiazoleꢀ4ꢀcarboxylate (2) and bis[2ꢀ(2ꢀpyridylthiꢀ
azolꢀ4ꢀylcarbonyloxy)ethyl] disulfide (4) is described. The complexation of compounds 2 and 4
with CuII, CoII, and NiII chlorides and perchlorates has been studied. Electrochemical behavꢀ
ior of the ligands and complexes obtained has been investigated by cyclic voltammetry and
using rotating disk electrode, which allowed us to confirm the possibility for the ligand 4 and its
complexes to be adsorbed on the surface of a gold electrode.
Key words: copper(II), cobalt(II), nickel(II), transition metal complexes, thiazoles, ligands,
electrochemistry.
2ꢀArylꢀ and hetarylꢀsubstituted imidazoles, oxazoles,
Results and Discussion
and thiazoles belong to an important class of biologically
active compounds.1—6 It is known7 that in many cases,
a coordination with transition metal ions increases antiviral
and antitumor activity of drugs. From this point of view,
the thiazoles containing 2ꢀpyridyl substituent at position 2
and capable of giving chelate fiveꢀmembered metallacyꢀ
cles on complexation are of significant interest.
The copper(II) complexes with organic N,Sꢀcontainꢀ
ing ligands capable of reversible reduction to the metal(I)
complexes also attract attention as functional models of
metalloenzymes and electroactive catalysts.8 In this conꢀ
nection, it is desirable to obtain new complexes of this
class, especially those containing additional disulfide
groups remote from the chelating fragment and capable of
providing "binding" of the metal complex to the surface of
metallic electrodes.
Synthesis of ligands and complexes. In the literature,
there are described two basic methods for the preparation
of 2ꢀsubstituted thiazolecarboxylic acids: the oxidative deꢀ
hydrogenation of thiazolidines10 and the reaction of thioꢀ
amides with bromo ketones11. On comparison of these
methods with regard to the synthesis of 2ꢀ(2ꢀpyridyl)ꢀsubꢀ
stituted thiazole, we found that attempted oxidation of
ethyl ester of the corresponding substituted thiazolidine
with Nꢀbromosuccinimide (NBS) resulted in a complex
mixture of products and failure to isolate the target comꢀ
pound. In contrast to this, the reaction of thioamide 1
(obtained by the reaction of 2ꢀcyanopyridine with hydroꢀ
gen sulfide) and ethyl 3ꢀbromoꢀ2ꢀoxopropiolate leads to
ethyl 2ꢀ(2ꢀpyridyl)thiazoleꢀ4ꢀcarboxylate (2) in 74% yield
(Scheme 1).
Earlier,9 we have synthesized a number of organic
ligands of the 2ꢀ(2ꢀpyridyl)ꢀsubstituted benzothiazole seꢀ
ries and shown that they are promising organic ligands for
producing transition metal complexes. In the present work,
we describe the synthesis of two structurally close ligands
of the 2ꢀ(2ꢀpyridyl)ꢀsubstituted thiazole series and their
complexes with CoII, CuII, and NiII salts. For one of
the ligands under consideration with a disulfide fragment
in the structure, a possibility of its adsorption on the
surface of a gold electrode with subsequent complexation
and formation of stable metallocomplex surfaces has
been found.
Ethanol or diethyl ether can also be used for the reacꢀ
tion with ethyl 3ꢀbromoꢀ2ꢀoxopropiolate, however, DMF
provides the highest yield of the product.
The hydrolysis of ester 2 to the corresponding acid 3
and subsequent esterification with di(2ꢀhydroxyethyl) disꢀ
ulfide in the presence of DCC and DMAP afforded ligand
4 (Scheme 2).
To sum up, we synthesized ligand 4 capable of both to
be adsorbed on the gold surface due to the presence of the
disulfide fragment and to undergo complexation due to
the presence of the donating pyridine and thiazole nitroꢀ
gen atoms, as well as its more simple analog 2 with similar
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 826—832, April, 2009.
1066ꢀ5285/09/5804ꢀ0844 © 2009 Springer Science+Business Media, Inc.

Complexes of thiazoles
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 4, April, 2009
845
Scheme 1
ple, whereas the compositions of the complexes with coꢀ
balt chloride (6) and copper perchlorate (7) were conꢀ
firmed by elemental analysis.
Scheme 3
2 + MCl2•6H2O → M(2)Cl2
5, M = Cu (18%)
6, M = Co (22%)
2 + Cu(ClO4)2•6H2O → Cu(2)(ClO4)2
7 (24%)
In an effort to synthesize complexes of the ligand 2
with NiCl2•6H2O and Ni(ClO4)2•6H2O, no crystalline
complexes were obtained. Nevertheless, the complexꢀ
ation with nickel chloride was detected electrochemically
(see below).
Scheme 2
No crystalline complexes were obtained in such a way
for the ligand 4, however, the change in color of solution
on mixing of the ligand 4 and metallic salt solutions sugꢀ
gests that complexation takes place in the solution.
The complexation in this case is also confirmed by the
results of electrochemical studies (see below).
The crystallographic data for the copperꢀcontaining
complex 5, experimental details, and refining parameters
of the structure are given in Table 1. Molecular structure
of compound 5 is shown in Fig. 1, selected bonds distancꢀ
es and bond angles are given in this Figure captions. The
copper atom in the complex 5 has a tetrahedral ligand
surrounding and is coordinated by the nitrogen atoms of
C(6)
C(8)
S(1)
C(5)
C(4)
C(1)
C(2)
C(3)
C(7)
N(1)
N(2)
C(9)
coordinating fragment, but more soluble in most organic
solvents due to the absence of a disulfide group.
O(1)
Cu(1)
Cl(2)
O(2)
The complexes were synthesized by a slow diffusion of
a metallic salt solution in MeCN into the ligand solution
in CH2Cl2. The salts CoCl2•6H2O, CuCl2•6H2O, and
Cu(ClO4)2•6H2O were used in this method to obtain comꢀ
plexes for ligand 2. When metallic chlorides are used
(Scheme 3), there are formed complexes of the form
M(2)Cl2 (M = Cu (5), Co (6)); in the reaction with copꢀ
per perchlorate, the composition of the complex correꢀ
sponds to the molecular formula Cu(2)2(ClO4)2 (7). The
structures of the complexes obtained were inferred from
the Xꢀray diffraction data using compound 5 as an examꢀ
C(10)
Cl(1)
C(11)
Fig. 1. Molecular structure of complex 5. Selected bond distancꢀ
es (Å) and bond angles (deg): Cu(1)—N(1) 2.002(4); Cu(1)—N(2)
2.025(4); Cu(1)—Cl(1) 2.198(2); Cu(1)—Cl(2) 2.222(2);
N(1)—Cu(1)—N(2) 80.3(2); N(1)—Cu(1)—Cl(1) 148.1(2);
N(2)—Cu(1)—Cl(1) 98.5 (1); N(1)—Cu(1)—Cl(2) 99.2(1);
N(2)—Cu(1)—Cl(2) 136.7(2); Cl(1)—Cu(1)—Cl(2) 102.9(1).

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Russ.Chem.Bull., Int.Ed., Vol. 58, No. 4, April, 2009
Majouga et al.
Table 1. Crystallographic data, experimental details, and refinꢀ
ing parameters for the structure of compound 5
Table 2. Oxidation (EOx) and reduction (ERed) potentials for
ligands 2 and 4 and their complexes measured by the CVA and
RDE methods (rel. Ag|AgCl|KCl sat.) on GFC(Au) electrode in
a
DMF in the presence of 0.1 M Bu4NClO4
Parameter
Value
Molecular formula
Molecular weight
T/K
C11H10Cl2CuN2O2S
368.71
Red
Red
Ox
Ox
Comꢀ
pound
Epc
E1/2
Epc
E1/2
V
296(2)
Wavelength/Å
Type of crystal
Size of crystal/mm
Crystal system
Space group
Parameters of unit cell
a/Å
b/Å
0.71073
2
5
–1.79/–1.72
–2.12 b
–1.80 (1)
—
—
Green needles
0.6×0.2×0.1
Triclinic
0.44/0.52 c
–1.80
0.42 (1) c
–1.81 (1)
1.18 1.30 (2)
1.28 1.23(2)
Pꢀ1
–2.33
6
7
–1.15/0.08 –1.12 (1.3) d
7.7230(15)
8.5480(17)
11.638(2)
94.93(3)
106.04(2)
108.13(3)
689.2(3)
2
–1.80/–1.72
0.06/0.12 c
–0.34/0.10 –0.34 (0.9)
–1.76/–1.70 –1.79 (1.8)
–1.85 (1)
0.07 (0.9) c
—
—
c/Å
α/deg
β/deg
2 + NiCl2• –1.23/0.02 –1.12 (1.6) d
1.16 1.17 (2)
1.16 (2)
γ/deg
•6Н2О –1.79/–1.72
–1.83 (1)
V/Å3
(in situ)
Z
4 –1.56
–1.56 (1)
–2.07/–2.00
–2.63
1.16 b
–1.87 (1)
dcalc/g cm–3
1.777
2.120
370
Absorption coefficient/mm–1
F(000)
4e + CuCl2• 0.30/0.38 c
—
1.09
0.93
—
Range of θ/deg
Ranges of reflection indices
1.85—29.96
0 ≤ h ≤ 10,
–12 ≤ k ≤ 11,
–15 ≤ l ≤ 15
4274/
•6Н2О
–0.85
–1.97 b
–0.85
4e + NiCl2•
— 1.06
1.37
•6Н2О
–1.28/0.27
–1.91 b
Number of measured/
independent reflections
3996
a Epc, potentials of cathode peaks (200 mV s–1)/potentials of reꢀ
verse peaks; E1/2, potentials of halfꢀwave measured by the RDE
method (2800 rpm). The number of electrons determined by
comparison with the height of a oneꢀelectron wave of the oxidaꢀ
tion of ferrocene is given in parentheses.
(Rint
)
(0.0808)
173
0.990
Number of refining variables
Reliability on F2
RꢀFactors (I > 2σ(I))
R1
0.0583
0.0958
b Peak of low intensity.
wR2
c Initial potential, 0.7 V.
RꢀFactors (on all the data)
R1
wR2
d In the experiments on RDE, the electrode processes are comꢀ
plicated by the covering of the surface with a zeroꢀvalence metal
(M0), the electroreduction takes place on the modified surface,
that leads to a drop in the current and does not allow one to
precisely determine the number of transmitted electrons.
e Ligand 4 adsorbed on the surface of Au electrode.
0.2402
0.1325
the pyridine and thiazole rings and two chloride anions.
The thiazole and pyridine rings of the molecule are virtuꢀ
ally coplanar.
Electrochemical study of compounds 2 and 4 and their
complexes. Ligands 2 and 4 and their complexes were studꢀ
ied by cyclic voltammetry (CVA) and rotating disk elecꢀ
trode method (RDE) in DMF solutions on a glassꢀfilled
carbon (GFC), Pt and Au electrodes in the presence of 0.1
M Bu4NClO4 as an indifferent electrolyte. The potentials
of electrochemical oxidation and reduction measured relꢀ
atively to Ag|AgCl|KCl(sat.) are given in Table 2. Cyclic
zation of molecular geometry was made with the set gradiꢀ
ent of convergence no more than 10 cal Å–1 mol–1), both
the HOMO and the LUMO of the ligand 2 are mainly
localized on the thiazole fragments. Cosequently, the iniꢀ
tial oxidation and reduction should occur at the cyclic
fragment. However, no peaks are observed in the region of
oxidation: apparently, the oxidation of ligand 2 should
occur at more anodic potentials.
voltamograms are given in Fig. 2.
The study of electrochemical reduction of the copperꢀ
containing complex 5 using CVA exhibits a oneꢀelectron
quasiꢀreversible reduction at the copper atom (Scheme 4)
at Epc = 0.44 V (see Fig. 2, b).
The intermediate containing CuI is stable when studꢀ
ied on a GFC electrode. This fact is confirmed by the
The reduction of ligand 2 (GFC electrode) takes place
in two steps, the first of which (Epc = –1.79/–1.72 V) is
reversible (see Fig. 2, a). According to the data of quanꢀ
tum chemical calculations (ab initio SCF method PM312
including into the Hyperchem program package; optimiꢀ

Complexes of thiazoles
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 4, April, 2009
847
a
b
5μA
5 μA
1.0
0
–1.0
–2.0 E/V
1.0
0
–1.0
–2.0 E/V
c
d
5 μA
5 μA
0
–1.0
E/V
2.0
1.0
0
–1.0
–2.0 E/V
e
f
5 μA
2 μA
1.0
0
–1.0
–E/V
1.0
0
–1.0
–2.0 E/V
g
h
2 μA
5 μA
1.0
0
–1.0
–2.0
E/V
1.0
0
–1.0
–2.0 E/V
Fig. 2. Cyclic voltamgrams (GFC electrode (unless other electrode material is specified), DMF, 0.1 M Bu4NClO4): a, ligand 2
(10–3 mol L–1), b, complex 5 (5•10–4 mol L–1), c, complex 5 (5•10–4 mol L–1, Au electrode), d, complex 7 (5•10–4 mol L–1),
e, complex 7 (5•10–4 mol L–1, Au electrode), f, complex 6 (5•10–4 mol L–1), g, ligand 4 (5•10–4 mol L–1), h, ligand 4 (5•10–4 mol L–1
,
Au electrode).

848
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 4, April, 2009
Majouga et al.
Scheme 4
of the voltꢀampere curve. This testifies that a twoꢀelectron
reduction at the metal initially takes place, the zeroꢀvalent
cobalt complex obtained is unstable and decomposes to the
ligand 2 and metallic cobalt. The second reversible cathode
peak corresponds to the reduction of the free ligand (see
Fig. 2, f). The oxidation of complex 6 occurs at Eрa = 1.28 V,
that corresponds to the reduction of chloride anions.
The complex of ligand 2 with NiCl2 was obtained only
in solution in situ. The mixing of ligand 2 and NiCl2•6H2O
in DMF solution exhibits the change of the solution color
and the emergence on the voltamograms of irreversible cathꢀ
ode peak of the complex reduction at Epc = –1.23 V instead
of the peak of NiCl2 reduction at Epc = –1.32 V (see Table 2).
The CVA curves of this complex on the whole are similar
to those for complex 6, that testifies basically the
same mechanism of electroreduction for both complexes
(see Table 2).
To sum up, the complexes of ligand 2 with CoII and
NiII chlorides under study undergo a twoꢀelectron reducꢀ
tion "at the metal" in the first step and decompose with the
liberation of metallic cobalt or nickel and the free ligand;
the copperꢀcontaining complexes 5 and 7 in the first step
undergo a oneꢀelectron reduction to the stable copper(I)
complexes. After the second cathodic oneꢀelectron proꢀ
cess, the complex 7 containing perchlorate ions decomꢀ
poses with the liberation of metallic copper and the free
ligand, whereas the complex 5 does not undergo destrucꢀ
tion under these conditions (on the GFC electrode). On
the Pt and Au electrodes, the CuIꢀcontaining intermediꢀ
ates disproportionate at a noticeable rate.
absence of the peak of oxidative desorbtion of metallic
copper from the electrode on the reverse scan of the CVA
curve even after the potential Epc = –2.0 V was reached.
In addition, the peak corresponding to the reduction
of the ligand is irreversible for the complex 5, in contrast
to the first cathode peak of the free ligand (see Table 2,
Fig. 2, b).
When the study was carried out on an Au electrode,
similarly to the GFC electrode, the complex 5 is stable in
solution unlike, for example, Cu(creat)2Cl2 (creat means
creatinine (2ꢀaminoꢀ1ꢀmethylꢀ1,5ꢀdihydroꢀ4Hꢀimidazolꢀ
4ꢀone)),13 the electroreduction of which is preceded by
decomposition of the complex to the starting components.
However, it should be noted that on the metallic elecꢀ
trodes (to a lesser extent, on the Pt electrode and to
a greater, on the Au electrode), a disproportionation of
the intermediate CuI(2)Cl2 (obtained by a oneꢀelectron
reduction) to the complex 5 and Cu0 compound takes
place. The copper(0) complex apparently decomposes with
the liberation of metallic copper (Scheme 5), that leads to
the cathode shift of the reoxidation peak and increase in
its intensity (see Table 2, Fig. 2, c).
Scheme 5
The reduction of ligand 4 (GFC electrode) occurs at
less negative potentials (Epc = –1.56 V) than the reducꢀ
tion of ligand 2 (see Fig. 2, g).
According to the data of quantum chemical calculaꢀ
tions, both the HOMO and the LUMO of ligand 4 are
localized mainly on the disulfide fragment, in contrast to
ligand 2 where they were localized on the benzothiazole
fragments. Apparently, the irreversible reduction of ligand
4 occurs initially at the disulfide fragment to form the
thiolate anions. The second reversible peak of the reducꢀ
tion is observed at Epc = –2.07 V. When the ligand 4 is
studied on the Au electrode, already the first scans exhibit
a new peak at Epc = –0.88 V (see Table 2, Fig. 2, h)
apparently related to the reduction of the fragment Au—S
(see Refs 14—16) with the simultaneous decrease in the
intensity of the cathodic peak, which corresponds to the
electroreduction of the S—S bond. If the electrode is kept
in a solution of this ligand for 20 h, the peak at Epc = –
1.56 V completely disappears. Apparently, this is due to
the fact that the disulfide fragment present in the starting
molecule disappears during adsorption because of the
cleavage of the S—S bond with the generation of the Au—S
bond and the formation of a monolayer.
i. Fast.
Such disproportionation processes on Pt and Au elecꢀ
trodes were also observed during electroreduction of the
complex 7. On the GFC electrode, the first peak of reducꢀ
tion, as for 5, is a oneꢀelectron and quasiꢀreversible, that
testifies the stability of the copper(I) complex. But after
the second cathode peak (Epc = –0.34 V, CuI(2)(ClO4)2 →
→ Cu0(2)(ClO4)2) on the reverse scan of the voltꢀampere
curve, the peak of the desorption of metallic copper is
observed (Eрa = 0.08 V; see Table 2, Fig. 2, d, e). Thus, the
stability of complex 7 containing perchlorate ions is lower
than the stability of complex 5 having chloride ions in its
structure.
On the CVA curves of the complex with CoCl2 (6),
there is additional peak of reduction at Epc= –1.15 V as
compared to the ligand, after which the peak of the desꢀ
orption of metallic cobalt is observed on the reverse scan
If the Au electrode modified with ligand 4 is kept in
a solution of metallic salt (Cu2+, Ni2+) for 30 min and

Complexes of thiazoles
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 4, April, 2009
849
a solution of Na2S•9H2O (0.42 g) and TEBAC (0.35 g) in water
(14 mL) were placed into a 250ꢀmL oneꢀneck thickꢀwall flask
equipped with a magnetic stirring bar, the flask was filled with
dry H2S and heated to 70 °C for 3 h with vigorous stirring on a
water bath in the flow of H2S. A precipitate of thioamide formed
was filtered off and recrystallized from EtOH to obtain thioamꢀ
ide 1 (49.56 g, 72%) as yellow crystals. M.p. 138—140 °C
(cf. Refs 19 and 20: m.p. 137—138 °C). 1H NMR (DMSOꢀd6), δ:
9.56 (br.s, 1 H, NH); 8.71 (d, 1 H, αꢀPy, J = 7.8 Hz); 8.52 (d, 1 H,
β´ꢀPy, J = 4.5 Hz); 8.11 (br.s, 1 H, NH); 7.84 (td, 1 H, βꢀPy,
J1 = 7.8 Hz, J2 = 1.8 Hz); 7.45 (dd, 1 H, γꢀPy, J1 = 4.51 Hz,
J2 = 1.0 Hz).
Ethyl 2ꢀ(2ꢀpyridyl)thiazoleꢀ4ꢀcarboxylate (2). Ethyl 3ꢀbroꢀ
moꢀ2ꢀoxopropiolate (1.41 g, 7.2•10–3 mol) was added to thioaꢀ
mide 1 (1 g, 7.2•10–3 mol) in DMF (10 mL). The mixture was
heated for 3 h on a water bath at 100 °C with stirring. The solvent
was evaporated under reduced pressure to obtain ester 2 (1.19 g,
74%) as a dark brown oil. 1H NMR (DMSOꢀd6), δ: 8.63 (d, 1 H,
PyꢀαꢀH, J = 4.9 Hz); 8.35 (d, 1 H, Pyꢀβ´ꢀH, J = 7.9 Hz); 8.27
(s, 1 H, thiazole); 7.84 (d, 1 H, PyꢀβꢀH, J = 6.2 Hz); 7.37 (t, 1 H,
PyꢀγꢀH, J = 6.2 Hz); 4.47 (q, 2 H, CH2, J = 7.2 Hz); 1.45
(t, 3 H, Me, J = 7.1 Hz). IR, ν/cm–1: 1730 (C=O).
washed followed by recording voltamgrams in a pure soluꢀ
tion of the electrolyte, then the CVA curves in both cases
exhibit peaks identical to those observed for the correꢀ
sponding complexes with a model ligand 2. This fact conꢀ
firms the formation on the surface of coordination comꢀ
pounds of similar structure.
In conclusion, there have been isolated CuII and CoII
complexes with 2ꢀ(2ꢀpyridyl)thiazoleꢀ4ꢀcarboxylic esters
including ester 4 containing a disulfide group remote from
the chelating 2ꢀpyridylthiazole fragment; the complexꢀ
ation of this ligand with NiII in solution has been detected
electrochemically. For the ligand 4, a possibility of its
adsorption on the surface of Au electrode has been demꢀ
onstrated with subsequent formation of metallocomplex
surfaces. Further, we plan to study possible catalytic acꢀ
tivity of the complexes synthesized in the reactions of oxiꢀ
dation and electroꢀinduced reduction.
Experimental
The reaction course was monitored by TLC on Silufol plates
2ꢀ(2ꢀPyridyl)thiazoleꢀ4ꢀcarboxylic acid (3). Potassium hydrꢀ
oxide (0.13 g, 2.33•10–3 mol) in EtOH—H2O (1 : 1, 10 mL)
was added to a solution of ester 2 (0.36 g, 1.56•10–3 mol) in the
same mixture of solvents (10 mL) followed by stirring for 3 h
and addition of 1 M HCl to pH = 2. A precipitate was filtered off
to obtain acid 3 (0.217 g, 68%) as light brown crystals. M.p.
224—226 °C. 1H NMR (CDCl3), δ: 8.67 (d, 1 H, PyꢀαꢀH,
J = 4.7 Hz); 8.57 (s, 1 H, thiazole); 8.16 (d, 1 H, Pyꢀβ´ꢀH,
J = 7.9 Hz); 7.84 (d, 1 H, PyꢀβꢀH, J = 6.2 Hz); 7.37 (t, 1 H,
PyꢀγꢀH, J = 6.2 Hz). MS, m/z (Irel (%)): 208 [MH]+ (73).
Bis[2ꢀ(2ꢀpyridylthiazolꢀ4ꢀylcarbonyloxy)ethyl] disulfide (4).
Di(2ꢀhydroxyethyl) disulfide (0.08 g, 4.8•10–4 mol), dicycloꢀ
hexylcarbodiimide (0.22 g, 9.7•10–4 mol), and 4ꢀdimethylamiꢀ
nopyridine (0.02 g, 1.6•10–4 mol) were added to a solution of
acid 3 (0.2 g, 9.7•10–4 mol) in dichloromethane (20 mL) folꢀ
lowed by stirring for 11 h. The solvent was evaporated at reduced
pressure. The residue was recrystallized from EtOH. The yield
was 0.115 g (45%). M.p. >300 °C. Found (%): C, 49.99; H, 3.30;
N, 10.31. C22H18N4O4S4. Calculated (%): C, 49.81; H, 3.40;
N, 10.57. 1H NMR (DMSOꢀd6), δ: 8.64 (d, 1 H, PyꢀαꢀH,
J = 7.0 Hz); 8.62 (s, 1 H, thiazole); 8.14 (d, 1 H, Pyꢀβ´ꢀH,
J = 7.0 Hz); 8.00 (d, 1 H, PyꢀβꢀH, J = 7.0 Hz); 7.55 (t, 1 H,
PyꢀγꢀH, J = 7.1 Hz); 4.58 (t, 2 H, CH2CO, J = 6.2 Hz); 3.22
(t, 2 H, CH2S, J = 6.2 Hz).
Preparation of complexes with ligand 2 (general procedure).
A solution of thiazole 2 (0.045 g, 0.085 mmol) in dichloromethane
(1 mL) was placed into a testꢀtube followed by a slow (along the
testꢀtube wall) addition to it of acetonitrile (200 μL) so as to
form a twoꢀphase system. Then, a solution of metallic salt
(0.085 mmol) in acetonitrile (1 mL) was slowly added to it. The
reaction mixture was tightly capped and left to form crystals (for
2—3 days). The solvent was decanted from the crystals formed,
which were dried in air.
Copper 4ꢀethoxycarbonylꢀ2ꢀ(2ꢀpyridyl)thiazole dichloride (5).
The yield was 0.0054 g (18%), dark green crystals. Found (%):
C, 36.23; H, 2.73; N, 7.64. C11H10Cl2CuN2O2S. Calculated (%):
C, 36.82; H, 2.79; N, 7.81.
1
with a bound layer of silica gel. H and 13C NMR spectra were
recorded on a Varian—Mercuryꢀ400 or Bruker—Evanceꢀ400
spectrometers (400 MHz) at 25 °C in deuterated chloroform and
DMSOꢀd6. IR spectra were recorded on a URꢀ20 spectrometer
in Nujol. Mass spectra were recorded on a Finnigan MAT SSQ
7000 GCꢀMS spectrometer (70 eV, an OVꢀI quartz capilꢀ
lary column (25 m), the temperature mode: 70 °C (2 min)—
20 °C min–1—280 °C (10 min)).
Xꢀray diffraction analysis was performed on a CADꢀ4 monocꢀ
rystal automatic diffractometer (a graphite monochromator,
λ(MoꢀKα) = 0.71073 Å, ωꢀscanning). The structure was decodꢀ
ed by the direct method (SHELXSꢀ97)17 and refined in the fullꢀ
matrix anisotropic least squares merhod on F2 for all nonhydroꢀ
gen atoms (SHELXLꢀ97).18 All the hydrogen atoms were localꢀ
ized objectively and refined in the isotropic approximation.
A PIꢀ50ꢀ1.1 potentiostate was used for the electrochemical
studies, which was connected to a PRꢀ8 programator. A glassꢀ
filled carbon (d = 2 mm), platinum (d = 3 mm), and gold
(d = 2 mm) disks were used as working electrodes, 0.1 M solution
of Bu4NClO4 in DMF as a background electrolyte, Ag/AgCl/KCl
(sat.) as a comparison electrode, platinum plate as an auxiliary
electrode. The surfaces of working electrodes were polished with
the powder of aluminum oxide with particle <10 μm in size
(Sigma—Aldrich). The potential scanning rate in the CVA methꢀ
od was 200 mV s–1, in the RDE method, 20 mV s–1. The potenꢀ
tials are given with allowance for the iRꢀcompensation. The
number of transmitted electrons in the redoxꢀprocesses was deꢀ
termined by comparison of the maximum wave current value in
the experiments on the RDE with the current of a oneꢀelectron
oxidation of ferrocene taken in the same concentration.
All the measurements were performed under dry argon; samꢀ
ples were dissolved in a degassed solvent. DMF (pure grade) was
purified by stirring over freshly calcined K2CO3 for 4 days with
subsequent distillation in vacuo first over P2O5, then, over anhyꢀ
drous CuSO4.
2ꢀPyridinethiocarboxamide (1) was obtained according to the
modified procedure described earlier.19,20 A solution of 2ꢀpyꢀ
ridinecarbonitrile (10 g, 0.096 mol) in benzene (50 mL) and
Cobalt 4ꢀethoxycarbonylꢀ2ꢀ(2ꢀpyridyl)thiazole dichloride (6).
The yield was 0.0066 g (22%), dark blue crystals. Found (%):

850
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 4, April, 2009
Majouga et al.
C, 36.40; H, 2.61; N, 7.64. C11H10Cl2CoN2O2S. Calculated (%):
C, 36.26; H, 2.75; N, 7.69.
Copper bis[4ꢀethoxycarbonylꢀ2ꢀ(2ꢀpyridyl)thiazole] diperꢀ
chlorate (7). The yield was 0.0066 g (22%), dark red crystals.
Found (%): C, 39.23; H, 3.01; N, 8.18. C22H20Cl2CuN4O12S2.
Calculated (%): C, 39.61; H, 3.00; N, 8.40.
7. J. A. Grim, H. G. Petring, Cancer Res., 1967, 27, 1278.
8. B. Xie, L. J. Wilson, D. M. Stanbury, Inorg. Chem., 2001,
40, 3606.
9. E. K. Beloglazkina, I. V. Yudin, A. G. Majouga, A. A. Moiꢀ
seeva, A. I. Tursina, N. V. Zyk, Izv. Akad. Nauk, Ser. Khim.,
2006, 1738 [Russ. Chem. Bull., Int. Ed., 2006, 55, 1803].
10. B. Baker, G. Lourens, J. Med. Chem., 1969, 12, 95.
11. V.ꢀM. Mukkala, P. Liitti, I. Hemmilä, H. Takalo, C. Mataꢀ
chescu, J. Kankare, Helv. Chim. Acta, 1996, 79, 295.
12. J. J. P. Stewart, J. Comput. Chem., 1989, 10, 209.
13. B. S. ParanjonꢀKosta, E. J. Baran, O. E. Piro, Polyhedron,
1997, 16, 3379.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 07ꢀ03ꢀ00584ꢀa).
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Received March 13, 2008;
in revised form September 10, 2008