Thiazolo[4,5-d]thiazole - A new domain for potential optoelectronic application

Article abstract of DOI:10.1016/j.tetlet.2010.08.110

A novel heterocyclic moiety based on thiazolo[4,5-d]thiazole was prepared via a six-step synthesis from butane-2,3-dione. This thiazolothiazole compound was further derivatized to afford either neutral conjugated condensation products or analogous N-alkyl salts. The obtained derivatives represent dipolar structures expressed as A-π-D (push-pull compounds) as well as quadrupolar D-π-A-π-D structures. Both types of compound show intramolecular charge transfer and therefore could be suitable for nonlinear optical applications.

Full text of DOI:10.1016/j.tetlet.2010.08.110

Tetrahedron Letters 51 (2010) 5819–5821
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Thiazolo[4,5-d]thiazole—a new domain for potential optoelectronic application
⇑
Peter Zahradník, Peter Magdolen , Pavol Zahradník
Department of Organic Chemistry, Faculty of Natural Sciences, Comenius University, SK-842 15 Bratislava, Slovakia
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel heterocyclic moiety based on thiazolo[4,5-d]thiazole was prepared via a six-step synthesis from
butane-2,3-dione. This thiazolothiazole compound was further derivatized to afford either neutral conju-
gated condensation products or analogous N-alkyl salts. The obtained derivatives represent dipolar struc-
tures expressed as A-p-D (push–pull compounds) as well as quadrupolar D-p-A-p-D structures. Both
types of compound show intramolecular charge transfer and therefore could be suitable for nonlinear
Received 21 June 2010
Revised 6 August 2010
Accepted 31 August 2010
Available online 7 September 2010
optical applications.
Keywords:
Ó 2010 Elsevier Ltd. All rights reserved.
Thiazolothiazole
Condensation
Push–pull system
Optoelectronic
The search for new organic molecules with possible applica-
tions in optoelectronics is of considerable interest.1 From the
appropriate candidates, aromatic heterocycles provide strong po-
tential advantages for several electro-optic and nonlinear-optic
applications due to their suitable electronic structures and chemi-
cal, photochemical, and thermal stability.2
was prepared by high temperature synthesis.7 Starting from chlo-
ral amides some p-substituted 2,5-diphenylthiazolo[4,5-d]thia-
zoles were synthesized recently.8
In this Letter we report a six-step synthesis of 2,5-dimethyl-
thiazolo[4,5-d]thiazole 5, the product of its methylation, 2,3,5-
trimethyl thiazolothiazolium iodide 8, and some of their condensa-
In continuation of our research in the field of new thiazole-
based heterocycles with optical nonlinearities, we have studied
the thiazolothiazole structural motif as an aromatic system with
tion products of the structural type A-p-D with a thiazolothiazole
core or a 3-methylthiazolothiazolium core as an acceptor, a
dimethylamino donor and an ethene or styrene linker.
p-deficient acceptor capacity. Two isomeric thiazolothiazoles are
Quantum chemical calculations9 show isomer 1a to be more
stable by about 3 kJ/mol than 1b. The C2h symmetry with a center
of symmetry is the reason for the zero dipole moment of 1a, while
the dipole moment of isomer 1b with C2v symmetry equals
2.5 ꢀ 10ꢁ30 C.m. This electronic structure brings nonlinearity to
molecule 1b and its derivatives. The synthetic route to the target
molecule is outlined in Scheme 1.
possible, namely thiazolo[5,4-d]thiazole (1a) and thiazolo[4,5-
d]thiazole (1b).
S
N
S
N
N
S
S
N
1a
1b
Starting oxime 2 was prepared by a known three-step synthesis
from butane-2,3-dione.10 The Beckmann rearrangement under the
described conditions11 was shown to be impractical due to the
Compound 1a and its substituted derivatives are functional
materials used in the field of organic semiconductors.3 Recent
research showed that the thiazolothiazole system is a promising
candidate as a core unit for high performance semiconductors.4
Unlike more common derivatives of compound 1a which have
found practical optoelectronical applications, there is little known
on the synthesis and properties of isomer 1b.
S
N
S
S
N
O
S
N
b
a
N
H
N
H
N
4
2
3
HO
Although several cyclic thiocarbamates with structures com-
prising the thiazolo[4,5-d]thiazole skeleton have been prepared,5,6
only few fully aromatic derivatives of 1b have been synthesized.
One such example is 2,5-dichlorothiazolo[4,5-d]thiazole which
S
N
S
N
c
5
Scheme 1. Reagents and conditions: (a) PCl5, 1,4-dioxane, rt, 4 h, 73%; (b)
Lawesson’s reagent, THF, MW, 100 °C, 10 min, 88%; (c) K3[Fe(CN)6], NaOH/H2O/
EtOH, rt, 82%.
⇑
Corresponding author. Tel.: +421 2 60296603; fax: +421 2 60296337.
E-mail address: magdolen@fns.uniba.sk (P. Magdolen).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.08.110

5820
P. Zahradník et al. / Tetrahedron Letters 51 (2010) 5819–5821
a
R
S
N
S
N
S
N
S
N
6a
6b
7
9a
9b
1.0
0.8
0.6
0.4
0.2
0.0
b
6a R =p-Me2NC6H4
6b R =p-Me2NC6H4-CH=CH
c
R
S
N
S
N
R
7 R =p-Me2NC6H4
R
S
N
S
N
S
N
S
N
d
I
I
8
9a R =p-Me2NC6H4
9b R =p-Me2NC6H4-CH=CH
200
300
400
500
600
700
Scheme 2. Reagents and conditions: (a) RCHO, KOH, DMSO, rt, 2 h, 6a (94%), 6b
(37%); (b) RCHO, NaH, THF, reflux, 2 h, 56%; (c) MeI, MeOH, MW, 100 °C, 15 min,
97%; (d) RCHO, MeOH, MW, 100 °C, 20 min, 9a (66%), 9b (75%).
Wavelenght (nm)
Figure 1. Normalized absorption spectra of the prepared conjugated thiazolo[4,5-
d]thiazole derivatives.
reaction time 14 days, so we investigated other conditions. Neither
a change of catalyst nor an elevated temperature satisfied the
requirements. However, variation of the solvent led to a substantial
decrease of the reaction time when cyclic ethers were used. 1,4-
Dioxane was preferred over THF as the latter partially reacts with
PCl5 to form hard to separate chlorinated by-products. Amide 3
was converted into thioamide 4 using Lawesson’s reagent under
microwave conditions (100 °C, 3 bar, 10 min) and finally thiazolo-
thiazole 5 was obtained in 82% yield via Jacobsen cyclization using
aqueous potassium ferricyanide as the oxidant.12 The total yield of
5 obtained by the sequence in Scheme 1 was 53%; when calculated
from butane-2,3-dione the overall yield was 15%. The structure of
the new heterocyclic system in 5 was confirmed by its 1H NMR
spectrum, when only one signal was evident (2.83 ppm for methyl
groups) and especially by its 13C NMR spectrum, where three dif-
ferent signals for aromatic carbons were observed (two small ones
at 120.6 and 170.0 ppm for ring junction carbons and one more in-
tense signal at 168.3 ppm typical for position 2 in a thiazole ring).
The potential of compound 5 to form conjugated systems
suitable for nonlinear optical materials was demonstrated by fur-
ther derivatization (Scheme 2). Due to the acidic character of the
methyl groups this compound undergoes Knoevenagel-type reac-
tion with aromatic aldehydes. Thus, the reaction with p-dimethyl-
aminobenzaldehyde in DMSO catalyzed by KOH afforded product
6a in 94% yield,13 and with p-dimethylamino-cinnamyl aldehyde
gave 6b in 37% yield. Dimethylthiazolothiazole 5 reacted under
these reaction conditions only on one side and the products repre-
intense absorption band in the UV–vis spectra measured in CHCl3.
The position of the long wavelength maxima in 6a and 6b is very
similar (about 400 nm), compound 6b shows a higher extinction
coefficient than 6a.
The corresponding charge transfer from the dimethylamino
group to the heterocycle is more effective in the thiazolothiazoli-
um salts 9a and 9b. This effect results in an intense long wave-
length band in the region above 500 nm (in methanol). The two
double bonds in conjugated linker 9b result in a bathochromic shift
of the long wave band in comparison with the one double bond in
9a. The absorption spectra shown in Figure 1 were measured in
CHCl3 for neutral compounds and in MeOH for the salts with the
following parameters: kmax/nm (log
(4.48), 7 428 (4.27), 9a 514 (4.64), 9b 546 (4.53).
Another type of structure with quadrupolar D-
e): 6a 408 (4.30), 6b 400
p
-A-p-D is repre-
sented by compound 7. The dipolar and/or quadrupolar structures
of the prepared compounds together with the stable heterocyclic
core make these products potential nonlinear optical (NLO)
materials.
In summary, a new route to thiazolo[4,5-d]thiazole derivatives
with alkyl substituents, based on Jacobsen cyclization has been
developed. The products can be further derivatized by condensa-
tion reaction forming dipolar or quadrupolar conjugated molecules
which are applicable as NLO materials.
Acknowledgment
sent a dipolar structure of type A-p-D. In order to prepare thiazol-
othiazoles derivatized on both sides, it was necessary to use a more
powerful solvent and stronger base. Thus, 7 was synthesized from
the same starting materials as 6a, but using THF and 2 equiv of
NaH instead of DMSO/KOH led to completion of the reaction. The
The authors are grateful to the Slovak Research and Develop-
ment Agency (grant APVV No. 0259-07) for financial support.
References and notes
condensation product 7 is considered as a type D-p-A-p-D struc-
ture; these are typical substances used for two-photon absorbance
materials.
1. Nalwa, H. S.; Watanabe, T.; Miyata, S. In Nonlinear Optics of Organic Molecules
and Polymers; CRC Press, 1997; pp 89–350.
2. Miller, R. D.; Lee, V. Y.; Moylan, C. R. Chem. Mater. 1994, 6, 1023–1032.
3. Li, W.; Katz, H. E.; Lovinger, A. J.; Laquindanum, J. G. Chem. Mater. 1999, 11,
458–465.
4. Ando, S.; Nishida, J.; Inohue, Y.; Tokito, S.; Yamashita, Y. J. Mater. Chem. 2004,
14, 1787–1790.
5. Singh, M. J. Bull. Chem. Soc. Jpn. 1968, 41, 2183–2184.
6. Schaefer, V. H.; Bartho, B.; Gewald, K. J. J. Prakt. Chem. 1977, 319, 149–158.
7. Beck, G.; Heitzer, H.; Holtschmidt, H. Synthesis 1985, 586–591.
8. Demydchuk, B. A.; Brovarets, V. S.; Vasilenko, A. N.; Drach, B. S. Heteroat. Chem.
2008, 19, 677–681.
The acidity of the methyl group in 5 was enhanced by quatern-
ization of the skeletal nitrogen forming a thiazolium salt. Methyl-
ation of
5 with iodomethane under microwave conditions
(100 °C, 5 bar, 15 min) afforded almost quantitatively, 2,3,5-tri-
methyl thiazolothiazolium iodide 8. This salt reacted with the alde-
hydes mentioned above and conjugated salts 9a and 9b were
obtained in 66%14 and 75% yields, respectively (Scheme 2). The
structures of all the salts were confirmed by spectral methods.
The neutral compounds 6a and 6b with A-p-D architecture rep-
resent dipolar structures with intramolecular charge transfer (ICT)
from the periphery D to heterocycle A. This fact results in an
ˇ
9. Kovác, Z.; Zahradník, P. Semi-Empirical AM1 Calculations, unpublished results.
10. De Maria, P.; Fontana, A.; Arlotta, M.; Chimichi, S.; Spinelli, D. J. Chem. Soc.,
Perkin Trans. 2 1994, 415–420.
11. Benkoe, A.; Rotaru, I. Monatsh. Chem. 1975, 106, 1027–1032.

P. Zahradník et al. / Tetrahedron Letters 51 (2010) 5819–5821
5821
12. Compound 5. To the stirred solution of K3[Fe(CN)6] (20 mmol) in H2O (25 mL),
a suspension of 4 (0.861 g, 5 mmol) in 10% NaOH (18 mL) and EtOH (20 mL)
was added dropwise, then the mixture stirred for 45 min at rt. The product was
extracted with CHCl3 (5 ꢀ 30 mL), the combined organic layer dried over
Na2SO4, the solvent removed by evaporation and the crude product purified by
column chromatography (silica gel, hexane/AcOEt 1:1) to give 0.697 g (82%)
white solid, mp 100–101 °C. 1H NMR (300 MHz, CDCl3): 2.83 (s, 6H). 13C NMR
(75 MHz, CDCl3): 170.0, 168.3, 120.6, 20.5. IR (ATR): 2919, 1508, 1405, 1377,
((300 MHz, CDCl3): 7.45 (d, J = 8.0 Hz, 2H), 7.41 (d, J = 16.2 Hz, 1H), 7.12 (d,
J = 16.2 Hz, 1H), 6.70 (d, J = 8.0 Hz, 2H), 3.02 (s, 6H), 2.84 (s, 3H). IR (ATR): 3027,
2976, 2908, 2804, 1595, 1525, 1363, 1226, 1165, 945, 803 cmꢁ1. HRMS: calcd
for C15H16N3S2 [M+H]+ 302.0786, found 302.0798.
14. Compound 9a.
A
solution of
8
(0.15 g, 0.48 mmol) and 4-
dimethylaminobenzaldehyde (0.13 g, 0.906 mmol) in MeOH (2 mL) capped in
a 5 mL vial was irradiated in a microwave reactor to 100 °C for 15 min with
stirring. After cooling to rt the resulting dark solid was filtered, washed with
cold MeOH, cold acetone and dried to give 0.14 g (66%) of 9a, mp 229–230 °C.
1H NMR (300 MHz, DMSO-d6): 7.95 (d, J = 15.6 Hz, 1H), 7.84 (d, J = 8.7 Hz, 2H),
7.42 (d, J = 15.6 Hz, 1H), 6.81 (d, J = 8.7 Hz, 2H), 4.19 (s, 3H), 3.08 (s, 6H), 2.86 (s,
3H). 13C NMR (75 MHz, DMSO-d6): 175.0, 171.4, 155.4, 152.9, 145.9, 132.0,
121.6, 118.6, 111.9, 107.2, 39.8, 36.4, 20.2. IR (ATR): 2902, 1567, 1531, 1505,
1450, 1374, 1279, 1154, 941, 810, 794 cmꢁ1. HRMS: calcd for C16H18N3S2þ [M]+
316.0937, found 316.0940.
1368, 1167, 1128, 1119, 1073, 993 cmꢁ1. UV–vis (MeOH): kmax/nm (log
e): 222
(4.30), 266 (3,86). HRMS: calcd for C6H7N2S2 [M+H]+ 171.0045, found
171.0050.
13. Compound 6a. To
a
solution of
5
(0.192 g, 0.7 mmol) and 4-
dimethylaminobenzaldehyde (0.157 g, 1.05 mmol) in DMSO (3 mL) three
drops of 50% KOH were added. The mixture was stirred for 3 h at rt, the
precipitated solid filtered, washed with a small amount of cold MeOH and
dried to give 0.201 g (94%) of 6a as an orange solid mp 224–227 °C. 1H NMR