Unusual result of the reaction of 4-(1-methyl-1 H-imidazol-2-yl)methylene- substituted 2-alkylthioimidazol-5(4H)-one with copper(II) chloride

Article abstract of DOI:10.1007/s11172-011-0327-0

A reaction of potassium ({(4Z)-4-[(1-methyl-1H-imidazol-2-yl)methylene]-5- oxo-1-phe-nyl-4,5-dihydro-1 H-imidazol-2-yl}thio)acetate with copper(II) chloride in methanol leads to bis(5-anilino-7-methoxycarbonyl-1-methyl-1H- imidazo[1,2-c]pyrimidin-4-ium) tetrachloro-cuprate(II), whose structure was confirmed by the X-ray diffraction studies.

Full text of DOI:10.1007/s11172-011-0327-0

Russian Chemical Bulletin, International Edition, Vol. 60, No. 10, pp. 2120—2123, October, 2011
2120
Unusual result of the reaction of 4ꢀ(1ꢀmethylꢀ1Hꢀimidazolꢀ2ꢀyl)methyleneꢀ
substituted 2ꢀalkylthioimidazolꢀ5(4H)ꢀone with copper(II) chloride
A. V. Yudina, A. G. Mazhuga, E. K. Beloglazkina, I. V. Yudin, I. A. Rodin, and N. V. Zyk
M. V. Lomonosov Moscow State University, Department of Chemistry,
1, str. 3 Leninskie Gory, 119991 Moscow, Russian Federation.
Eꢀmail: bel@org.chem.msu.ru
A reaction of potassium ({(4Z)ꢀ4ꢀ[(1ꢀmethylꢀ1Hꢀimidazolꢀ2ꢀyl)methylene]ꢀ5ꢀoxoꢀ1ꢀpheꢀ
nylꢀ4,5ꢀdihydroꢀ1Hꢀimidazolꢀ2ꢀyl}thio)acetate with copper(II) chloride in methanol leads to
bis(5ꢀanilinoꢀ7ꢀmethoxycarbonylꢀ1ꢀmethylꢀ1Hꢀimidazo[1,2ꢀc]pyrimidinꢀ4ꢀium) tetrachloroꢀ
cuprate(II), whose structure was confirmed by the Xꢀray diffraction studies.
Key words: 2ꢀalkylthioimidazolꢀ5(4H)ꢀone, 1ꢀmethylꢀ1Hꢀimidazole, imidazopyrimidines.
In continuation of our studies of 5ꢀhetarylmethyleneꢀ
substituted 2ꢀthioxoimidazolꢀ4ꢀones, their Sꢀalkylated deꢀ
rivatives, and the CuII complexes with these organic comꢀ
pounds,1—4 we used a twoꢀstep sequence of reactions of
3ꢀphenylꢀ2ꢀthiohydantoin 1 and 1ꢀmethylꢀ2ꢀimidazoleꢀ
carbaldehyde with the intermediate formation of a potasꢀ
sium salt of (4Z)ꢀ2ꢀmercaptoꢀ4ꢀ[(1ꢀmethylꢀ1Hꢀimidazolꢀ
2ꢀyl)methylene]ꢀ1ꢀphenylimidazolꢀ5(4H)ꢀone (2) to synꢀ
thesize a new ligand from the series of 5ꢀsubstituted
2ꢀalkylthioꢀ3,5ꢀdihydroꢀ4Hꢀimidazolones, viz., potassiꢀ
um ({(4Z)ꢀ4ꢀ[(1ꢀmethylꢀ1Hꢀimidazolꢀ2ꢀyl)methylene]ꢀ
5ꢀoxoꢀ1ꢀphenylꢀ4,5ꢀdihydroꢀ1Hꢀimidazolꢀ2ꢀyl}thio)ꢀ
acetate (3), (Scheme 1).
Note that the attempt to synthesize 2ꢀacetoxythioꢀsubꢀ
stituted 1ꢀphenylimidazolꢀ5(4H)ꢀone 3 by the reaction of
sodium bromoacetate with the potassium salt 2 did not
lead to the target product: the starting reactants were isoꢀ
lated from the reaction mixture. Apparently, the lower
electrophilicity of the anion of bromoacetic acid as comꢀ
pared to the corresponding ester interferes with the proꢀ
ceeding the nucleophilic substitution reaction for the
bromine atom. If ethyl bromoacetate was used in the reacꢀ
tion, ethyl ({4ꢀ[(1ꢀmethylꢀ1Hꢀimidazolꢀ2ꢀyl)methylene]ꢀ
5ꢀoxoꢀ1ꢀphenylꢀ4,5ꢀdihydroꢀ1Hꢀimidazolꢀ2ꢀyl}thio)ꢀ
acetate A is apparently formed initially, which undergoes
E2ꢀelimination in the presence of sodium ethoxide, yieldꢀ
ing ethylene and the target salt 3 (Scheme 2).
When we studied a reaction of compound 3 with
copper(II) chloride, an unusual result was obtained
(Scheme 2): the imidazopyrimidinium salt 4 was isolated
from the reaction mixture in 22% yield instead of the exꢀ
pected coordination compound 4´.
The structure of compound 4 was confirmed by the
data of Xꢀray diffraction analysis (Fig. 1). The crystalloꢀ
graphic data, details of the experiment, and parameters of
refinement for the structure 4 are given in Table 1. All the
atoms of the heterobicyclic fragment are placed in one
plane; the exocyclic nitrogen atom and atoms of the benzꢀ
ene ring are in this plane, as well. In the crystal, the moleꢀ
cules are arranged in stacks with the parallel orientation of
the aromatic fragments.
Scheme 3 shows a possible mechanism for the formaꢀ
tion of imidazopyrimidinium cation. In the first step of
the reaction, a Lewis acid (CuCl2) catalyzed imidazolone
Scheme 1
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2083—2085, October, 2011.
1066ꢀ5285/11/6010ꢀ2120 © 2011 Springer Science+Business Media, Inc.

Imidazo[1,2ꢀc]pyrimidinium
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 10, October, 2011
2121
Scheme 2
ring opening in compound 3 occurs with a solvent (methꢀ
anol) molecule. Further, recyclization takes place, also
catalyzed with CuCl2, with the formation of the cation of
compound 4 and elimination of the sulfurꢀcontaining
fragment.
The reaction discovered is the first example of the
formation of imidazopyrimidine ring in the reacꢀ
tions of imidazolylmethyleneꢀsubstituted dihydroimidꢀ
azolones.
Experimental
The reaction progress was monitored by thinꢀlayer chromatoꢀ
graphy (TLC) on silica gel precoated plates (Silufol plates).
1H NMR spectra were recorded on a Bruker Avance 400 spectroꢀ
meter in CDCl3 and DMSOꢀd6 at 25 °C. IR spectra were reꢀ
corded on a URꢀ20 spectrometer in Nujol. Mass spectra were
recorded on a Shimadzu LCMS 2010A instrument in the chemꢀ
ical ionization version at the atmospheric pressure in the positive
Scheme 3

2122
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 10, October, 2011
a
Yudina et al.
Table 1. Crystallographic data, details of experiment, and refineꢀ
ment parameters for the structure of compound 4
Parameter
Value
C(104)
C(103)
Molecular formula
Molecular weight
Crystal form
Crystal size/mm
Crystal system
Space group
a/Å
b/Å
с/Å
α/deg
β/deg
C
30H30Cl4CuN8O4
772
Black prisms
N(11)
C(105)
0.36×0.34×0.085
C(109)
N(12)
C(106)
Triclinic
N(14)
–
C(110)
P1
N(13)
10.6220(12)
12.105(3)
13.8875(17)
96.482(14)
111.191(10)
91.612(13)
1649.7(5)
2
C(107)
C(108)
b
γ/deg
V/Å3
Z
dcalc/g cm–3
μ/mm–1
1.5536
1.036
F(000)
790
Region of scanning, θ/deg
Region of h, k, l
2.00—29.99
0 < h < 14
–17 < k < 17
–19 < l < 19
9592
+
Fig. 1. The structure of the cation C15H15N4O2 (a) and the
molecule (b) in compound 4. Selected bond distances/Å:
N(11)—C(109) 1.299(2), C(105)—N(12) 1.339(2), C(105)—N(13)
1.369(3), N(12)—C(106) 1.460(3), N(12)—C(107) 1.373(3),
N(13)—C(109) 1.394(2), C(109)—N(14) 1.348(3), N(14)—C(110)
1.420(2); selected bond angles/deg: N(11)—C(103)—C(104)
124.48(18), C(103)—N(11)—C(109) 119.51(15), N(12)—
C(105)—N(13) 107.08(17), N(12)—C(107)—C(108) 108.95(19),
N(11)—C(109)—N(13) 120.44(17).
Number of measured reflections
Number of independent reflections
Number of refined parameters
Qꢀfactor on F2
Rꢀfactors on reflections with I > 2σ(I )
R1
wR2
6665
544
1.18
0.0348
0.0490
Rꢀfactors (on all the data)
R1
wR2
ions mode. Xꢀray diffraction studies were performed on a CADꢀ4
monocrystal automatic diffractometer (graphite monochromaꢀ
tor, λ(MoꢀKα) = 0.71069 Å, ωꢀscanning) at 293 K.
0.0348
0.0490
3ꢀPhenylꢀ2ꢀthiohydantoin (1) was obtained according to the
published procedure.5
(4Z)ꢀ2ꢀMercaptoꢀ4ꢀ[(1ꢀmethylꢀ1Hꢀimidazolꢀ2ꢀyl)methylꢀ
ene]ꢀ1ꢀphenylimidazolꢀ5(4H)ꢀone potassium salt (2). 1ꢀMethylꢀ
2ꢀimidazolecarbaldehyde (0.29 g, 2.6 mmol) was added to a soluꢀ
tion of thiohydantoin 1 (0.5 g, 2.6 mmol) in the minimum amount
of 2% aqueous KOH and this was stirred at room temperature for
3 h. A precipitate that formed was filtered off and dried in air to
obtain compound 2 (0.64 g, 76%) as an orange powder. M.p.
310 °C. 1H NMR (DMSOꢀd6), δ: 3.75 (s, 3 H, CH3); 6.00 (s, 1 H,
=CH); 7.26 (dd, 2 H, Ph, J1 = 8.2 Hz, J2 = 1.1 Hz); 7.31
(m, 3 H, Ph and CHimid); 7.41 (m, 2 H, Ph and CHimid). IR,
ν/cm–1: 2950, 1680. MS, m/z: 285 [M — K + 2 H]+ (100).
Found (%): C, 52.36; H, 3.87; N, 16.94. C14H11KN4OS. Calcuꢀ
lated (%): C, 52.15; H, 3.44; N, 17.38.
({(4Z)ꢀ4ꢀ[(1ꢀMethylꢀ1Hꢀimidazolꢀ2ꢀyl)methylene]ꢀ5ꢀoxoꢀ1ꢀ
phenylꢀ4,5ꢀdihydroꢀ1Hꢀimidazolꢀ2ꢀyl}thio)potassium acetate (3).
Metallic sodium (0.02 g) and compound 2 (0.2 g, 0.62 mmol)
were sequentially dissolved in EtOH (5 mL), followed by addiꢀ
tion of ethyl bromoacetate (0.12 g, 0.7 mmol) to the reaction
mixture, which was stirred for 4 h. A precipitate that formed was
filtered off, washed with water, and dried in air to obtain comꢀ
pound 3 (0.115 g, 85%) as a yellow powder. M.p. 340 °C.
1H NMR (CDCl3), δ: 3.50 (s, 2 H, CH2); 3.82 (s, 3 H, CH3);
6.68 (s, 1 H, =CH); 7.37—7.43 (m, 3 H, Ph and CHimid);
7.48—7.61 (m, 4 H, Ph and CHimid). 13C NMR (CDCl3), δ:
34.6, 38.0, 108.8, 125.5, 128.2 (2 C); 129.6, 129.9 (2 C); 131.3,
133.1, 137.6, 144.7, 164.0, 166.2, 167.4. IR, ν/cm–1: 3380 (br),
3120, 3135, 1750, 1600. Found (%): C, 46.09; H, 4.07; N, 12.79;
S, 7.60. C16H13KN4O3S•2H2O. Calculated (%): C, 46.14;
H, 4.11; K, 9.39; N, 13.45; O, 19.21; S, 7.70.
Bis(5ꢀanilinoꢀ7ꢀmethoxycarbonylꢀ1ꢀmethylꢀ1Hꢀimidazoꢀ
[1,2ꢀc]pyrimidinꢀ4ꢀium) tetrachlorocuprate(II) (4). A solution of
CuCl2•2H2O (0.03 g, 1.4 mmol) in MeOH (2 mL) was added to
a solution of compound 3 (0.05 g, 1.4 mmol) in MeOH (2 mL),
the reaction mixture was tightly capped and kept for two days at
room temperature. The crystals that formed were filtered off,
washed with diethyl ether and dried in air to obtain compound 4
(0.22 g, 22%) as black crystals. M.p. 245—247 °C. Found (%):
C, 45.99; H, 3.77; N, 14.58. C30H30Cl4CuN8O4. Calculated (%):
C, 46.68; H, 3.92; N, 14.52.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 10ꢀ03ꢀ00677).

Imidazo[1,2ꢀc]pyrimidinium
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 10, October, 2011
2123
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Received March 29, 2011;
in revised form July 19, 2011