Tetrahedron Letters
Synthesis and evaluation of photophysical properties of Series
of p-conjugated oxazole dyes
Florence Mahuteau-Betzer a, , Sandrine Piguel a,b,
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a Institut Curie/CNRS, UMR 176, Bât. 110, Centre Universitaire, 91405 Orsay, France
b Univ. Paris-Sud, Orsay F-91405, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 23 January 2013
Revised 8 April 2013
Accepted 10 April 2013
Available online 16 April 2013
Incorporation of p-conjugated spacers at the 2 or 5 position of a 2,5-disubstitutedaryloxazole led to new
series of fluorescent dyes. They show emissions from visible to 700 nm along with significant Stokes shift
up to 208 nm and a strong solvatochromic fluorescence. These compounds are easily accessible in one
step through direct C–H bond functionalization.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Oxazole
Direct C–H bond functionalization
Fluorescence
Dyes
Discovering effective fluorescent molecules has been a long-
standing goal in the field of chemistry. Indeed, such photoactive
molecules find valuable applications as biomolecular probes, sen-
sor elements, and as building blocks in optical materials. Although
well-known fluorophores such as fluorescein, rhodamine, BODIPY,
and cyanines are currently used in many research fields, they do
not always satisfy the criteria of an ideal fluorophore: high absorp-
tion coefficient and quantum yield, a large Stokes shift, long life-
time, high chemical and photostability and, biocompatibility.
Therefore, there is a continuing interest in developing new fluores-
cent dyes.1,2 The 2,5-diaryloxazole unit is also an attractive build-
ing block for the construction of dyes with favorable photophysical
properties, due to its inherently strong absorption and lumines-
cence in the UV–vis spectrum, a large wavelength shift, and a high
quantum yield. Consequently, its derivatives have been the focus of
jugated spacers such as C@C double bonds or C„C triple bonds on
the C-2 or C-5 position of the oxazole core, in order to improve and
fine-tune the fluorescence properties. Considering the wide range
of possible applications, their synthesis needs to be straightfor-
ward. To meet this challenge, we have recently developed methods
based on the direct functionalization of C–H bond of azoles, and in
particular oxazoles, that allowed an efficient and rapid access to
such fluorescent dyes.17–22
Herein, we report the synthesis and the photophysical proper-
ties of new chromophores based on the oxazole scaffold substi-
tuted with styryl or alkynyl groups. The influence of these
structural changes on their fluorescence properties is discussed.
The synthetic route to the target molecules 7–20 relies on the
direct functionalization of C–H bonds of various 5-aryloxazoles
1–6 with aryl, vinyl or alkynyl bromides using previously reported
procedures (Schemes 1 and 2).
intensive work for the synthesis of p
-conjugated materials.3–8 2,5-
diaryloxazoles have already found use as tools for the detection of
radiolabelled bioanalytes and the determination of biological pro-
cesses such as protein activity and measurement of important ions,
such as Ca2+ and H+.9–14 Their two-photon properties have also
been recently reported for applications in multi-photon fluores-
cence microscopy.15,16 Therefore, the synthesis of even more-
evolved 2,5-disubstitutedoxazole fluorophores is of considerable
The 5-aryl oxazoles 1–6 were easily prepared in a single step by
the van Leusen reaction of the appropriate commercially available
aromatic aldehydes with p-toluenesulfonylmethylisocyanide (Tos-
MIC) and K2CO3 in refluxing MeOH. The 2,5-diaryloxazole deriva-
tives 7a, 7f, 8i, 8j, and 9k were prepared in moderate to good
yields by a direct arylation reaction through two different proto-
cols. In the case of 7a and 7f, a microwave-assisted palladium/cop-
per co-mediated direct arylation in DMF at 150 °C was used. While
for compounds 8i, 8j, and 9k, reaction conditions involving tetrakis
palladium complex in the presence of a strong base, tBuOLi, in
dioxane at 120 °C and the corresponding aryl bromide were imple-
mented. The E-5-aryl-2-styryloxazoles 10b–d, 11b, 12a,c and 13k
were synthesized, as a single stereoisomer, by a copper-catalyzed
interest. In this context, we thought to incorporate classical p-con-
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Corresponding authors. Tel.: +33 169 867 159; fax: +33 169 075 381 (F.M.-B.);
tel.: +33 169 867 111; fax: +33 169 075 381 (S.P.).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.