Job/Unit: O30641
/KAP1
Date: 03-09-13 18:03:45
Pages: 9
Oxazolone-Based Photoswitches: Synthesis and Properties
isomerization for days at room temperature, and isomeriza-
tion was detected only after heating in toluene at 100°C.
Acknowledgments
This research was supported by the Spanish Ministerio de Ciencia
e Innovación (MICINN)/Fondos Europeos para el Desarrollo Re-
gional (FEDER) (CTQ2011-24800). M. B.-L. thanks the Spanish
Ministerio de Educación y Ciencia (MEC) for a grant.
Conclusions
We have presented a comprehensive study of the synthe-
sis and properties of a family of molecular photoswitches
inspired by the GFP chromophore. These compounds show
some features that make them promising candidates for use
as light-activated switches in different applications. Oxa-
zolone-based switches are easily synthesized in good yields
and several functional groups can be incorporated within
the basic structure. The choice of the substituents and sol-
vents can be made on the basis of the projected application
but also depending on the required photochemical features.
The high thermal and photochemical stabilities should pro-
vide these switches with desirable fatigue resistance. The
computational data allows an understanding of this key fea-
ture. The main drawback of oxazolones as photoswitches is
the nucleophilic ring opening, and this issue should be
solved before this type of compound could be used in bio-
logical applications. A detailed theoretical study of the
photoprocesses could provide the necessary data for the de-
sign of improved versions of these photoswitches and also
for tuning the switching properties to the requirements of
specific applications. Future work on these systems will
focus on the effect of light on these compounds once incor-
porated in complex systems.
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Experimental Section
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General Procedure for the Synthesis of Azalactones 2a–v: To a mix-
ture of amino acid 1 with the appropriate substituent R1 (1 equiv.,
20 mmol) and sodium acetate (1 equiv., 20 mmol) in acetic an-
hydride (18.4 mL), was added the corresponding aldehyde with the
required R2 group (1 equiv., 20 mmol). The resulting mixture was
stirred for 4 h at 100–110°C, then stirred overnight at 25°C. After
this time, the target azalactone precipitated and was separated by
filtration and washed with cold Et2O (100 mL). The resulting solid
was purified by flash chromatography on silica gel (hexanes/EtOAc,
2:1) to obtain the Z-isomer of 2a–v in 60–90% yield.
Theoretical Calculations: The common hybrid functional B3LYP
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Becke88,[22] and the HF exchange, as well as a mixture of the corre-
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ometry was fully optimized without any symmetry constraint for
all model compounds. Optimized structures were characterized as
minima or saddle points by frequency calculations, which also al-
lowed the ZPE and thermal corrections with no scaling factors to
be obtained. For transition structures, intrinsic reaction coordi-
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Gaussian 03 program package[27] was used for all calculations.
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Supporting Information (see footnote on the first page of this arti-
1
cle): Synthesis, characterization data and copies of the H and 13C
NMR spectra for switches 2. Figures S1–S3. Cartesian coordinates
for computed structures.
Eur. J. Org. Chem. 0000, 0–0
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