Microwave-assisted synthesis of 2,5-diarylthiazolo[5,4-d]thiazoles from benzaldehydes and dithiooxamide

Article abstract of DOI:10.1134/S1070428015030148

One-pot condensation of dithiooxamide with aromatic aldehydes and subsequent oxidation of intermediate 2,5-dihydro[1,3]thiazolo[5,4-d][1,3]thiazoles with selenium dioxide afforded 2,6-diaryl[1,3]thiazolo-[5,4-d][1,3]thiazoles which were characterized by <

Full text of DOI:10.1134/S1070428015030148

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2015, Vol. 51, No. 3, pp. 373–377. © Pleiades Publishing, Ltd., 2015.
Original Russian Text © L.K. Papernaya, A.A. Shatrova, I.V. Sterkhova, G.G. Levkovskaya, I.B. Rozentsveig, 2015, published in Zhurnal Organicheskoi
Khimii, 2015, Vol. 51, No. 3, pp. 389–393.
Microwave-Assisted Synthesis
of 2,5-Diarylthiazolo[5,4-d]thiazoles from Benzaldehydes
and Dithiooxamide
L. K. Papernaya, A. A. Shatrova, I. V. Sterkhova, G. G. Levkovskaya, and I. B. Rozentsveig
Favorskii Irkutsk Institute of Chemistry, Siberian Branch, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
e-mail: papern@irioch.irk.ru
Received October 29, 2014
Abstract—One-pot condensation of dithiooxamide with aromatic aldehydes and subsequent oxidation of inter-
mediate 2,5-dihydro[1,3]thiazolo[5,4-d][1,3]thiazoles with selenium dioxide afforded 2,6-diaryl[1,3]thiazolo-
[5,4-d][1,3]thiazoles which were characterized by 1H and 13C NMR, IR, and X-ray diffraction data.
DOI: 10.1134/S1070428015030148
Thiazolo[5,4-d]thiazoles constitute an important
class of bicyclic aromatic structures with two fused
thiazole rings, which are characterized by a rigid
planar skeleton and p-electron-deficient system
capable of being involved in efficient intermolecular
π–π interactions; therefore, these compounds possess
attractive properties from the viewpoint of their use in
electronics [1]. Fused thiazoles exhibit biological ac-
tivity and are used in medicine [2–4]. They also found
applications as components of photographic, semi-
conducting [2, 5–11], and optoelectronic materials
[12, 13], ligands for coordination chemistry [10, 14],
and liquid crystals [15]. Although the customer per-
formance of materials based on thiazolothiazoles have
been well documented, their synthetic chemistry has
been studied to a lesser extent, and problems related to
their synthesis remain topical.
aldehyde, which hampers isolation and purification of
the products. Alternative synthetic approaches to di-
arylthiazolo[5,4-d]thiazoles, e.g., treatment of 2,5-bis-
(acetylamino)thiazole with sodium thiocyanate in the
presence of bromine and subsequent thermally induced
cyclization [21] or acid-catalyzed reaction of 5-amino-
2-aryl-4-sulfanylthiazole with an ortho ester [22], as
well as other methods [1], have received only limited
application.
Dessi et al. [23] have recently proposed a procedure
for the synthesis of thiazolo[5,4-d]thiazoles via con-
densation of various aldehydes (aliphatic, aromatic,
and some heterocyclic) with dithiooxamide at a ratio of
4:1 or 2:1 [23]. The first step leading to intermediate
non-aromatic 2,5-dihydrothiazolo[5,4-d]thiazoles was
activated by microwave irradiation. In the second step,
the intermediate products were oxidized with chloranil
or 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ)
on heating in nitrobenzene–THF. However, the neces-
sity of two preparative steps and the use of expensive
and toxic oxidants hampered the isolation and purifica-
tion of the target products and increased the cost of the
process.
In the present work we tried to carry out the
synthesis of diarylthiazolo[5,4-d]thiazoles as a one-pot
process under microwave irradiation at both steps
(condensation of dithiooxamide with aromatic alde-
hydes and oxidative aromatization of intermediate
2,5-dihydrothiazolo[5,4-d]thiazoles). As oxidant in the
The main procedure for the synthesis of thiazolo-
[5,4-d]thiazole derivatives was proposed for the first
time in [16]; it was based on the condensation of di-
thiooxamide with excess aromatic aldehyde. The reac-
tions are carried out in various solvents such as o-di-
chlorobenzene [17], phenol [18, 19], nitromethane
[10], and DMF [10, 20] or under solvent-free condi-
tions [4, 6, 16]. However, harsh reaction conditions
(200°C) and long reaction time (24 h) favor tar forma-
tion and side processes, so that the yield of thiazolo-
[5,4-d]-thiazoles and their purity considerably de-
crease. The procedure requires 10–12 equiv of initial
373

PAPERNAYA et al.
374
Scheme 1.
R
S
S
CHO
MW, 150°C
NH2
N
+
H2N
N
R
S
N
S
R
1a–1c
H
R
S
N
S
SeO2
S
R
R
–Se
S
N
N
R
H
2a–2c
R = H (a), Cl (b), NO2 (c).
second step we used selenium dioxide which, unlike
chloranil and DDQ, is nontoxic and is converted into
elemental selenium that can be readily separated from
the reaction mixture.
under microwave irradiation in the same reaction
vessel (Scheme 1). After separation of elemental sele-
nium, thiazolo[5,4-d]thiazoles 2a–2c were isolated in
a good yield. Unlike the procedure described in [23],
the products required no additional purification by
column chromatography.
The condensation of aromatic aldehydes 1a–1c
with dithiooxamide (150°C, 30 min) and subsequent
oxidation with selenium dioxide (15 min) were carried
out in dimethylformamide at a reactant ratio of 2:1:2
Compounds 2a–2c are high-melting colored crys-
talline substances sparingly soluble in organic sol-
(a)
(b)
4.440
3.849
3.747
(c)
2.691
2.675
(a) Structure of the molecule of 2,5-bis(4-nitrophenyl)[1,3]thiazolo[5,4-d][1,3]thiazole (2c), (b) layered crystal structure of com-
pound 2c, and (c) unit cell with short N–O···HC contacts according to the X-ray diffraction data.
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MICROWAVE-ASSISTED SYNTHESIS OF 2,5-DIARYLTHIAZOLO[5,4-d]THIAZOLES
375
Bond lengths and bond and torsion angles in the molecule of 2,5-bis(4-nitrophenyl)[1,3]thiazolo[5,4-d][1,3]thiazole (2c)
Bond
d, Å
Bond angle
ω, deg
Torsion angle
φ, deg
S1–C6
O1–N1
C1–C4
C1–C5
N2–C6
C2–C3
C3–C4
C6–C6′
S1–C5
O2–N1
C1–C7
N2–C5
N1–C2
C2–C8
C6'–N2′
C7–C8
1.723(3)
1.202(4)
1.397(4)
1.467(4)
1.359(4)
1.366(4)
1.383(4)
1.364(5)
1.750(3)
1.217(4)
1.398(4)
1.315(3)
1.476(3)
1.379(4)
1.359(4)
1.378(4)
C6S1C5
C4C1C5
C5N2C6
O1N1C2
C3C2C8
C8C2N1
C3C4C1
N2C5S1
N2C6C6′
C4C1C7
C7C1C5
O1N1O2
O2N1C2
C3C2N1
C2C3C4
N2C6S1
00088.16(13)
119.3(2)
108.1(2)
118.4(3)
122.5(3)
118.2(3)
120.3(3)
116.2(2)
118.4(3)
119.0(2)
121.7(2)
123.9(3)
117.7(3)
119.3(3)
118.9(3)
132.4(2)
O1N1C2C3
O1N1C2C8
C8C2C3C4
C2C3C4C1
C5C1C4C3
C6N2C5S1
C7C1C5N2
C7C1C5S1
C6S1C5C1
C5S1C6C6′
C5C1C7C8
C3C2C8C7
O2N1C2C3
O2N1C2C8
N1C2C3C4
C7C1C4C3
–5.0(4)
175.9(3)
1.1(4)
–1.2(4)
–179.8(2)
0.2(3)
172.2(3)
–8.1(3)
179.7(2)
0.7(3)
–180.0(2)
–0.9(4)
173.9(3)
–5.1(4)
–177.9(2)
1.0(4)
vents. Their structure was confirmed by elemental
analyses and H and C NMR and IR spectra. The IR
irradiation. The procedure requires no excess aldehyde
and is much less laborious than known methods for the
preparation of thiazolo[5,4-d]thiazoles.
1
13
spectra of 2a–2c lacked carbonyl absorption bands
1
typical of initial aldehydes 1a–1c. The H NMR spec-
EXPERIMENTAL
tra of 2a–2c contained signals from aromatic protons
but no signal from aldehyde proton. Carbons atoms of
the thiazolo[5,4-d]thiazole fragment of 2a–2c resonat-
ed in the 13C NMR spectra at δC 150.9–151.41 (C1, C8)
and 167.8–169.2 ppm (C2, C6).
1
The H and 13C NMR spectra were recorded on
a Bruker DPX-400 spectrometer at 400.61 and
100.13 MHz, respectively, using tetramethylsilane as
internal standard. The IR spectra were recorded in KBr
on a Bruker Vertex 70 spectrometer. The melting
points were measured on a PolyTherm A hot stage
microscope. The microwave-assisted reactions were
carried out in an Anton Paar Monowave microwave
reactor in an inert atmosphere at a constant tempera-
ture (control probe) and variable power (up to 400 W).
The structure of 2c was unambiguously determined
by X-ray analysis (see figure and table). Molecule 2c is
planar (see figure, a), and the crystal structure of 2c is
layered with an interlayer distance of 3.74–4.44 Å (b).
A unit cell comprises five molecules. Short intermolec-
ular contacts are observed between hydrogen atoms of
the benzene rings and one oxygen atom of the NO2
group (2.68–2.69 Å; see figure, c). The principal bond
lengths and bond and torsion angles in molecule 2c are
given in table.
2,5-Diphenyl[1,3]thiazolo[5,4-d][1,3]thiazole
(2a). A microwave reactor vial equipped with a mag-
netic stirrer was charged with 0.212 g (2.0 mmol) of
aldehyde 1a, 0.120 g (1.0 mmol) of dithiooxamide, and
4 mL of DMF. The mixture was heated for 30 min at
150°C under microwave irradiation and cooled to
55°C, 0.228 g (2.0 mmol) of selenium dioxide was
added, and the mixture was stirred for 15 min at 200°C
and cooled to room temperature. The precipitate was
filtered off and recrystallized from THF. Yield 0.192 g
(65%), fine light yellow lustrous crystals, mp 209–
In summary, we have developed a simple and
efficient one-pot synthesis of thiazolo[5,4-d]thiazoles
by reaction of dithiooxamide with aromatic aldehydes
and subsequent oxidation of intermediate dihydrothia-
zolo[5,4-d]thiazoles. Selenium dioxide was used for
the first time as oxidant in the second step. Both reac-
tion steps are considerably accelerated by microwave
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 3 2015

PAPERNAYA et al.
376
2
212°C; published data: mp 209–210°C [16], 196–
198°C [24]. IR spectrum, ν, cm–1: 1499, 1456, 1428,
1319, 1221, 1032, 1007, 911, 887, 755, 684, 614.
1H NMR spectrum (CDCl3), δ, ppm: 7.46–7.53 m (3H,
m-H, p-H), 8.01–8.03 m (2H, o-H). 13C NMR spectrum
(CDCl3), δC, ppm: 126.49 (Cm), 129.21 (Co), 130.77
(Cp), 134.03 (Ci), 150.98 (C7, C8), 169.26 (C2, C6).
Found, %: C 64.90; H 3.38; N 9.32; S 21.49.
C16H10N2S2. Calculated, %: C 65.28; H 3.42; N 9.52;
S 21.78.
where P = (F0 + 2Fc2)/3. The positions of hydrogen
atoms were determined from the difference electron
density maps. The final divergence factor was R =
0.0604 [for 2744 reflections with I > 2σ(I) of 9301 re-
flections]. The complete set of crystallographic data
for compound 2c was deposited as CIF file to the
Cambridge Crystallographic Data Centre (entry
n o . C C D C 1 0 0 1 3 2 3 ) a n d i s a v a i l a b l e at
www.ccdc.cam.ac.uk/data_request/cif.
This study was performed under financial support
by the Siberian Branch of the Russian Academy of
Sciences (project no. 21) and by the Belarusian
Republican Foundation for Basic Research (project
no. Kh12SO-012). The spectral and analytical data
were obtained using the facilities of the Baikal Joint
Analytical Center, Siberian Branch, Russian Academy
of Sciences.
2,5-Bis(4-chlorophenyl)[1,3]thiazolo[5,4-d][1,3]-
thiazole (2b) was synthesized in a similar way from
0.281 g (2.0 mmol) of 4-chlorobenzaldehyde (1b).
Recrystallization from DMF gave fine light-yellow
powder with metallic luster. Yield 0.193 g (53%),
mp 291–293°C; published data [16]: mp 311–312°C.
IR spectrum, ν, cm–1: 1590, 1496, 1439, 1398, 1086,
1
1006, 841, 810, 659, 517, 499. H NMR spectrum
(C6D6), δ, ppm: 6.97–6.99 m (2H, m-H), 7.58–7.60 m
(2H, o-H). 13C NMR spectrum (C6D6), δC, ppm: 127.55
(Cm), 129.25 (Co), 132.51 (Ci), 136.48 (Cp), 151.41
(C7, C8), 167.83 (C2, C6). Found, %: C 52.65; H 2.13;
Cl 18.93; N 7.58; S 17.47. C16H8Cl2N2S2. Calculated,
%: C 52.90; H 2.22; Cl 19.52; N 7.71; S 17.65.
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 3 2015

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