Facile synthesis of 2,5-diarylthiazoles via palladium-catalyzed tandem C-H substitutions. Design of tunable light emission and liquid crystalline characteristics

Article abstract of DOI:10.1021/ja0289189

A mild and regioselective C-H substitution reaction of thiazole by the catalysis of the palladium/copper system is found to proceed in the presence of tetrabutylammonium fluoride under mild conditions. Applying the new reaction, we synthesized various 2,5

Full text of DOI:10.1021/ja0289189

Published on Web 01/22/2003
Facile Synthesis of 2,5-Diarylthiazoles via Palladium-Catalyzed Tandem C-H
Substitutions. Design of Tunable Light Emission and Liquid Crystalline
Characteristics
Atsunori Mori,* Akitoshi Sekiguchi, Kentaro Masui, Tomohiro Shimada, Masaki Horie,
Kohtaro Osakada, Masuki Kawamoto, and Tomiki Ikeda
Chemical Resources Laboratory, Tokyo Institute of Technology, 4259 Nagatsuta, Yokohama 226-8503, Japan
Received October 12, 2002 ; E-mail: amori@res.titech.ac.jp
The transition-metal-catalyzed reaction involving formation of
a C-C bond from a specific C-H bond has been a major challenge
in organic synthesis. Such a catalytic reaction has been shown to
proceed with several late transition metal complexes;1,2 however,
the major disadvantage of these reactions is that one has to apply
a relatively high reaction temperature, higher than 100 °C. In
particular, a catalytic substitution reaction of a C-H bond with an
organic halide has not been achieved so far at lower temperatures.
Herein, we report that the Pd/Cu-catalyzed C-H bond substitu-
tion reaction of thiazole (1) in the presence of tetrabutylammonium
fluoride (TBAF) as an activator takes place regioselectively under
mild conditions. With such a method, a variety of 2,5-diarylthiazole
derivatives are synthesized in facile and combinatorial manners.
Light-emitting and liquid crystalline characteristics of these mol-
ecules are investigated as potential EL materials with polarized light
emission.3,4
and Miura’s method leading to the differently substituted 2,5-
diarylthiazoles 6. The method is found to be effective to afford 6
because the alternative reaction site has already been substituted
with the preceding reaction. As summarized in Table 1, 2,5-
disubstituted derivatives bearing electron-donating and/or -with-
drawing substituents were synthesized via the tandem reactions in
moderate to excellent yields. The method would be suitable for
the combinatorial synthesis of a variety of 2,5-diarylthiazoles.
The λmax values of UV-vis absorption spectra of the obtained
thiazole derivatives were found to be influenced by the electronic
characteristics of the substituent. The peak of 6be bearing N,N-
dimethylamino and cyano groups was observed at 398 nm, while
that of 2-(4-methoxyphenyl)-5-(4-methylphenyl)thiazole (6ad) was
at 334 nm. In addition, most of these compounds obtained were
found to show light-emitting characteristics. Their wavelength and
intensities also depended on the type of substituents, suggesting
that the color of emission would be tunable by the electronic
property of the functional group. Considerably high photolumines-
cence quantum yields (Φ) were observed in thiazoles bearing an
N,N-dimethylamino group such as 6bg and 6be.
We have been studying a new class of coupling reactions of
terminal alkynes and have shown that TBAF serves as a novel and
excellent activator for the Pd/Cu-catalyzed reaction to undergo the
sp C-H substitution reaction with organic electrophiles.5 Hence,
we envisaged that sp2 C-H substitution would also take place
similarly.
Although synthesis of 2,5-diarylthiazoles has previously been
studied by condensation of (N-benzoyl)aminoacetophenone deriva-
tives (Aryl1COCH2NHCOAryl2) in the presence of P2S5, their yields
are generally lower (25-35%).7 By contrast, the tandem coupling
strategy allows us to afford 2,5-disubstituted thiazole with various
substituents in good yields and in a combinatorial manner, which
would be potential for the construction of the thiazole library.8
It was recently reported that 2,5-diaryl-1,3,4-oxadiazoles exhibit
liquid crystalline (LC) as well as light-emitting characteristics.9
Similar to those, a number of 2,5-diarylthiazoles synthesized were
found to show LC characteristics,7 which were evaluated by means
of DSC and polarizing microscopy. As summarized in Figure 1,
2,5-diarylthiazoles exhibited the LC phase in remarkably wide
ranges of temperature. For example, 6bg showed an LC phase
between 145 and 258 °C. The result markedly contrasts that of
oxadiazole 7 bearing the corresponding substituents, which shows
an LC phase between 138 and 143 °C.
Thiazole (1), which was a heteroaromatic compound bearing an
sp2 C-H bond, was chosen as an initial candidate for the coupling,
and the Pd/Cu-catalyzed reaction with 4-methoxy-1-iodobenzene
(2a) was examined in the presence of TBAF. When the reaction
was carried out in DMSO at 60 °C, 82% of the product coupled at
the 2-position (3a) was obtained as shown in eq 1. Worthy of note
is the lower reaction temperature, which is remarkably milder
among transition-metal-catalyzed C-H substitution with organic
electrophiles.1c,d The reaction at a further lower temperature, 40
°C or room temperature, also proceeded, although it took longer
reaction periods.6 It should also be pointed out that the course of
regiochemistry was highly controlled for the reaction to take place
at the 2-position. Only 6% of 2,5-diarylated product (4a) was
obtained, while monosubstituted product at the 5-position (5a) was
not observed at all. On the other hand, the related coupling reaction
catalyzed by palladium in the presence of K2CO3 or Cs2CO3 was
shown by Miura.1d The reaction is reported to proceed at 140 °C,
and the regioselectivity is markedly different from our results to
give 4 and 5, while no 2-substituted product 3 is obtained.
Redox behaviors of 2,5-diarylthiazoles were also investigated
by cyclic voltammetry.10,11 It appeared that the electrochemical
characteristics were also influenced by a substituent on the aromatic
ring. It was found that an electron-donating substituent played an
important role for oxidation. The more electron-donating -NMe2
group was easily oxidized as compared to -OMe. On the other
Because a facile preparation of 2-arylthiazole 3 is in hand, we
envisaged tandem coupling reactions applying the present reaction
9
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J. AM. CHEM. SOC. 2003, 125, 1700-1701
10.1021/ja0289189 CCC: $25.00 © 2003 American Chemical Society

C O M M U N I C A T I O N S
Table 1. Tandem Coupling of Thiazole and Absorption and Emission Properties of 3, 4a, and 6a
absorptionb
max, nm
(ꢀ, M-1 cm-1
emissionb
% yield
of 3
% yield
of 6
λ
λ
max, nm
Aryl1
Aryl2−X
product
)
(Φ)c
4-MeOC6H4- (2a)
82
none
C6H5I (2c)
3a
300 (10 800)
333 (28 000)
334 (22 800)
339 (22 300)
350 (30 200)
339 (27 900)
340 (25 400)
376 (38 200)
398 (26 900)
361 (0.21)
406 (0.22)
408 (0.17)
419 (0.17)
462 (0.27)
419 (0.24)
401 (0.19)
462 (0.49)
488 (0.37)
69
94
6ac
6ad
4a
6ae
6af
3b
4-MeC6H4I (2d)
4-MeOC6H4I (2a)
4-NCC6H4Br (2e)
4-nC6H13OC6H4I (2f)
none
62
76
4-Me2NC6H4- (2b)
80
4-(4-nC7H15C6H4)C6H4Br (2g)
2e
39d
26d
6bg
6be
a A thiazole derivative 3 was prepared with 3 mol % PdCl2(PPh3)2 and 2 mol % CuI (1/I-Aryl1/TBAF ) 2:1:2). Disubstituted thiazole 6 was synthesized
with Aryl2-X (2 equiv), CsCO3 (2 equiv), 10 mol % Pd(OAc)2, and 20 mol % PPh3 with stirring for 24-70 h. b Absorption spectra and emission spectra
were measured as a chloroform solution (1 × 10-5 and 3 × 10-6 M, respectively). c The quantum yield, Φ, was estimated by comparison of standard 1.0
M quinine sulfate (Φ ) 0.546). d The yield after recrystallization.
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Supporting Information Available: Experimental details and
analytical data (PDF). This material is available free of charge via the
Internet at http://pubs.acs.org.
JA0289189
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