Photoconversion of o-hydroxycinnamates to coumarins and its application to fluorescence imaging

Article abstract of DOI:10.1016/j.tetlet.2009.06.031

(E)-o-Hydroxycinnamates were synthesized and their photochemical behavior was investigated in liquid and solid states. It was confirmed by ¹H NMR spectroscopy that the (E)-o-hydroxycinnamates converted into the corresponding coumarins via (Z)-o-hydroxycinnamate intermediates. The photoconversion was greatly accelerated in the presence of p-toluenesulfonic acid. The optical properties of the cinnamates were compared with those of the corresponding coumarins. Fluorescence imaging was successfully accomplished by photoirradiation of PMMA films containing the cinnamates.

Full text of DOI:10.1016/j.tetlet.2009.06.031

Tetrahedron Letters 50 (2009) 4769–4772
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Photoconversion of o-hydroxycinnamates to coumarins and its application
to fluorescence imaging
Sung-Youl Cho a, Young-Kyu Song a, Joong-Gon Kim b, Se-Young Oh c, Chan-Moon Chung a,
*
a Department of Chemistry, Yonsei University, Wonju, Kangwon-do 220-710, South Korea
b Biotechnology Division, Hanwha Chemical R&D Center, Taejon 305-345, South Korea
c Department of Chemical and Biomolecular Engineering, Sogang University, Seoul 121-742, South Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
(E)-o-Hydroxycinnamates were synthesized and their photochemical behavior was investigated in liquid
and solid states. It was confirmed by 1H NMR spectroscopy that the (E)-o-hydroxycinnamates converted
into the corresponding coumarins via (Z)-o-hydroxycinnamate intermediates. The photoconversion was
greatly accelerated in the presence of p-toluenesulfonic acid. The optical properties of the cinnamates
were compared with those of the corresponding coumarins. Fluorescence imaging was successfully
accomplished by photoirradiation of PMMA films containing the cinnamates.
Received 20 March 2009
Revised 31 May 2009
Accepted 8 June 2009
Available online 11 June 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Recently the development of patterned fluorescent images in
polymer films attracted considerable interest due to their possible
application in the areas of displays, optical memory devices, and
molecular switches, as well as in the sensor and imaging indus-
tries.1 A typical method of the formation of fluorescent images em-
ploys photoirradiation through a photomask. In a conventional
chemisorption approach, reactive functional groups are generated
through photoacid-catalyzed deprotection, followed by a wet
developing process in which fluorescent dye molecules are at-
tached to the exposed areas through covalent bonding or intermo-
lecular interactions.2–4 A recently developed ‘precursor approach’
enables fluorescence imaging to be carried out without the need
for wet developing process. This approach includes photoacid-cat-
alyzed deprotection,5–8 photoinduced protonation,9–11 and photo-
generation of conjugated structure.12 The approach consists of
two steps, (1) photochemical acid generation from a photoacid
generator (PAG) and (2) post-exposure baking step for acid-in-
duced reactions. Photochromism is an alternative imaging method
that is based on a single photochemical step,13–16 but it includes
relatively complicated precursor synthesis.1
of the cinnamates were confirmed by 1H and 13C nuclear magnetic
resonance (NMR), Fourier transform infrared (FT-IR) spectroscopy,
and elemental analysis.
Photochemical behavior of the (E)-o-hydroxycinnamates was
investigated in liquid and solid states. First, we carried out photol-
Y
O
Y
OEt
hν
X
OH
(E)
OH
X
O
OEt
X = H; Y = H (CIN)
(Z)
X = OH; Y = H (HCIN)
X = OCH3; Y = H (MCIN)
X = OH; Y = OH (DHCIN)
Y
In this Letter we report a new method in which fluorescence
imaging can be accomplished via photoconversion of (E)-o-
hydroxycinnamate to coumarin. Our method does not need any
additional process such as wet developing and post-exposure bake.
In addition, our precursor compounds can be synthesized easily.
Four (E)-o-hydroxycinnamates (Scheme 1) have been prepared
by reacting salicylaldehydes with (carbethoxymethylene)triphen-
ylphosphorane.17–19 DHCIN was newly synthesized, and obtained
as pale yellow crystals in a yield of 97%. The chemical structures
Y
OH
- EtOH
X
O
OEt
X
O
O
X = H; Y = H (COUM)
X = OH; Y = H (HCOUM)
X = OCH3; Y = H (MCOUM)
X = OH; Y = OH (DHCOUM)
* Corresponding author. Fax: +82 33 760 2182.
E-mail address: cmchung@yonsei.ac.kr (C.-M. Chung).
Scheme 1. Photoconversion of (E)-o-hydroxycinnamates to coumarins.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.06.031

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S.-Y. Cho et al. / Tetrahedron Letters 50 (2009) 4769–4772
Figure 2. A plot of conversions of MCIN in PMMA films versus irradiation time: (a)
in the presence of TSA (mole ratio of MCIN:TSA = 1:0.2), and (b) without TSA. The
mass ratio of MCIN:PMMA was 1:2.33 and the films were prepared by casting.
similar to that of MCIN. It has been proposed that (Z) isomers of
o-hydroxycinnamates undergo intramolecular cyclization through
the nucleophilic addition of the o-hydroxy group onto the ethyl es-
ter moiety to give benzopyran hemiacetals, which finally convert
into coumarins (Scheme 1).18,20
We also studied the photoreaction of the cinnamates in the film
state. A solution of a cinnamate and poly(methyl methacrylate)
(PMMA) in tetrahydrofuran was cast and the solvent was removed
in vacuo at room temperature. After irradiation for a given period
of time at the wavelength of 300 nm, the film was dissolved in di-
methyl sulfoxide-d6. 1H NMR spectral analysis showed that the cin-
namates converted into their corresponding coumarins. However,
only a trace amount of (Z) form was detected in the NMR spectros-
copy during the photoreaction. It was thought that the intramolecu-
lar cyclization of (Z)-o-hydroxycinnamates to hemiacetal
intermediates occurred faster in the film state than in the liquid
state.
Figure 1. 1H NMR spectra showing the transformation of MCIN into MCOUM
(duration of photoirradiation in minutes: 0, 10, 120, and 210). A spectrum of an
authentic MCOUM is presented at the top for reference.
The degrees of conversion of MCIN to MCOUM (in the film state)
are shown as a function of irradiation time in Figure 2b. In order to
accelerate the lactonization of MCIN to MCOUM, we added a small
amount of p-toluenesulfonic acid (TSA) to the photoreactive for-
mulation, based on reports on acid-catalyzed lactonization of cin-
namic acids.21,22 As shown in Figure 2a, the photoconversion of
MCIN was greatly accelerated, and completed by irradiation for
4.5 min. Quantum yields for the photoconversion of cinnamates
into coumarins in the presence of TSA (20 mol % with respect to
cinnamate) were measured in the film state. When irradiated at
328 m, CIN, HCIN, MCIN, and DHCIN showed quantum yields of
0.29, 0.51, 0.39, and 0.39, respectively.
We have determined the optical absorption and emission spec-
tra of the cinnamates and coumarins in PMMA films. The absorp-
tion and fluorescence maxima are given in Table 1. The
absorption spectrum of MCIN in a thin PMMA film is shown in Fig-
ure 3a, and three main absorption bands are observed in the range
of 240–400 nm. The optical absorption of MCOUM is somewhat
lower than that of MCIN (Fig. 3b). Emission spectra of the cinna-
ysis of the cinnamates in ethanol. Typically, 200 mg of a cinnamate
was dissolved in 300 mL of ethanol and photolyzed with a photo-
reactor at a wavelength of 300 nm at room temperature. After pho-
tolysis, the photoproduct was obtained as white powders by
evaporating the solvent. It was confirmed by 1H NMR spectroscopy
that each cinnamate quantitatively afforded its corresponding cou-
marin (Scheme 1). The photoconversion of CIN and HCIN into
COUM and HCOUM, respectively, is in accordance with the previ-
ously reported results.18,20 As far as we know, there has been no re-
port on photochemical conversion of MCIN into MCOUM and
DHCIN into DHCOUM.
The course of the photoconversion of cinnamates into couma-
rins in liquid state was monitored by 1H NMR spectroscopy. MCIN
was dissolved in CD3CN, and irradiated in an NMR tube at the
wavelength of 300 nm. The 1H NMR spectral change of MCIN with
increasing exposure time is shown in Figure 1. The starting MCIN
showed vinylic proton peaks exhibiting a coupling constant of
16.0 Hz at 6.40 and 7.82 ppm. Upon irradiation for 10 min, new
vinylic protons exhibiting a coupling constant of 12.8 Hz appeared
at 5.82 and 7.05 ppm. This indicates that MCIN first converted into
its (Z) isomer through photoisomerization. When irradiated for
10 min, new vinylic protons exhibiting a coupling constant of
9.6 Hz also appeared at 6.20 and 7.79 ppm, indicating the forma-
tion of a small amount of MCOUM. The generation of ethanol along
with MCOUM formation was also observed in the NMR study (not
shown in Fig. 1). With increasing exposure time, the amount of
MCOUM increased while MCIN and its (Z) isomer gradually disap-
peared. The 1H NMR spectrum for the final product was the same
as that for an authentic MCOUM (Fig. 1). The other three cinna-
mates (CIN, HCIN, and DHCIN) showed photochemical behavior
Table 1
Optical absorption and fluorescence maxima wavelengths of cinnamates and
coumarins in PMMA films
Absorption (nm)
Fluorescence (nm)a
CIN
HCIN
MCIN
DHCIN
COUM
HCOUM
MCOUM
DHCIN
275, 325
242, 294, 330
240, 293, 328
320
274, 311
324
398
395
397
395
—
419
391
422
320
328
a
Excitation wavelength was 330 nm.

S.-Y. Cho et al. / Tetrahedron Letters 50 (2009) 4769–4772
4771
mates and coumarins in thin PMMA films are shown in Figure 4.
Fluorescence intensity of coumarins (HCOUM, DHCOUM, and
MCOUM) is much greater than that of the corresponding cinna-
mates (HCIN, DHCIN, and MCIN). In contrast, CIN showed much
higher fluorescence intensity than COUM. It is known that couma-
rins with either no substituent or no electron-withdrawing groups
in the 7-position are virtually non-emissive compared with those
having electron-donating groups.7,23 We expected that the usage
of CIN in fluorescence imaging would afford a ‘reverse’ image, com-
pared to the imaging with HCIN, DHCIN, and MCIN.
Preliminary fluorescent imaging was performed using the cin-
namates. Thin PMMA films containing each cinnamate were pre-
pared by spin coating. Irradiation of the films with light of k
>300 nm through a photomask resulted in a drastic change in the
luminescent property of the exposed areas due to the photoconver-
Figure 3. Optical absorption spectra of PMMA films containing (a) MCIN and (b)
MCOUM. The films were prepared at a concentration of 9.10 Â 10À5 mol of MCIN or
MCOUM in 0.070 g of PMMA by spin coating (film thickness: (a) 0.51 lm; (b)
0.45 lm).
Figure 4. Emission spectra of cinnamates and coumarins. The films were prepared at a concentration of 9.10 Â 10À5 mol of cinnamate (or coumarin) in 0.070 g of PMMA by
spin coating (film thickness: 0.43–0.51 lm, excitation wavelength: 330 nm).
Figure 5. Fluorescent images obtained with 0.50-
lm thick PMMA films containing (a) CIN and (b) MCIN (mass ratio of cinnamate:PMMA = 1:2.33 and mole ratio of
cinnamate:TSA = 1.0.2). The actual colors may slightly differ because of computer image processing. Width of the long, dark lines in the images is 30
l
m.

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S.-Y. Cho et al. / Tetrahedron Letters 50 (2009) 4769–4772
sion of cinnamate into coumarin. As shown in Figure 5 high-con-
trast fluorescent image patterns were successfully obtained. As ex-
pected, the exposed regions are dark (‘turn off’) in the case of CIN-
based film (Fig. 5a), but brightly colored (‘turn on’) in the case of
MCIN-based film (Fig. 5b). Thin PMMA films containing HCIN and
DHCIN gave fluorescent images similar to those containing MCIN.
In summary, four (E)-o-hydroxycinnamates were readily syn-
thesized from salicylaldehydes, and it was confirmed by 1H NMR
spectroscopy that the cinnamates photochemically converted into
their corresponding coumarins via (Z)-o-hydroxycinnamate inter-
mediates. Fluorescence imaging was accomplished for the first
time through the photoconversion of (E)-o-hydroxycinnamate to
coumarin. The photoconversion of (E)-o-hydroxycinnamates is
promising for the application to fluorescence imaging because
there is no necessity for any additional processes such as wet
developing and post-exposure bake, coupled with the ease of syn-
thesis of the precursors.
References and Notes
1. Kim, J.-M. Macromol. Rapid Commun. 2007, 28, 1191–1212.
2. Zhang, C.; Vekselman, A. M.; Darling, G. D. Chem. Mater. 1995, 7, 850–855.
3. Aoki, A.; Ghosh, P.; Crooks, R. M. Langmuir 1999, 15, 7418–7421.
4. Christman, K. L.; Requa, M. V.; Enriquez-Rios, V. D.; Ward, S. C.; Bradley, K. A.;
Turner, K. L.; Maynard, H. D. Langmuir 2006, 22, 7444–7450.
5. Kim, J.-M.; Kang, J.-H.; Han, D.-K.; Lee, C.-W.; Ahn, K.-D. Chem. Mater. 1998, 10,
2332–2334.
6. Yoo, J.-H.; Kim, S.-Y.; Cho, I.; Kim, J.-M.; Ahn, K.-D.; Lee, J.-H. Polymer 2004, 45,
5391–5395.
7. Frenette, M.; Coenjarts, C.; Scaiano, J. C. Macromol. Rapid Commun. 2004, 25,
1628–1631.
8. Yang, N. C.; Choi, H. W.; Lee, J. K.; Hwang, J. I.; Suh, D. H. Chem. Lett. 2002, 824–
825.
9. Kim, J.-M.; Chang, T.-E.; Kang, J.-H.; Park, K. H.; Han, D.-K.; Ahn, K.-D. Angew.
Chem., Int. Ed. 2000, 39, 1780–1782.
10. Pistolis, G.; Boyatzis, S.; Chatzichristidi, M.; Argitis, P. Chem. Mater. 2002, 14,
790–796.
11. Scaiano, J. C.; Laferriere, M.; Ivan, M. G.; Taylor, G. N. Macromolecules 2003, 36,
6692–6694.
12. Renak, M. L.; Bazan, G. C.; Roitman, D. Adv. Mater. 1997, 9, 392–395.
13. Lim, S.-J.; Seo, J.; Park, S. Y. J. Am. Chem. Soc. 2006, 128, 14542–14547.
14. Irie, M.; Fukaminato, T.; Sasaki, T.; Tamai, N.; Kawai, T. Nature 2002, 420, 759.
15. Fukaminato, T.; Sasaki, T.; Kawai, T.; Tamai, N.; Irie, M. J. Am. Chem. Soc. 2004,
126, 14843–14849.
Acknowledgment
16. Zhu, M.-Q.; Zhu, L.; Han, J. J.; Wu, W.; Hurst, J. K.; Li, A. D. Q. J. Am. Chem. Soc.
2006, 128, 4303–4309.
17. Bunce, R. A.; Schilling, C. L., III Tetrahedron 1997, 53, 9477–9486.
18. Gagey, N.; Neveu, P.; Benbrahim, C.; Goetz, B.; Aujard, I.; Baudin, J.-B.; Jullien, L.
J. Am. Chem. Soc. 2007, 129, 9986–9998.
This work was supported by the Korea Research Foundation
Grant funded by the Korean Government (MOEHRD) (KRF-2006-
521-C00122).
19. Ishii, H.; Kaneko, Y.; Miyazaki, H.; Harayama, T. Chem. Pharm. Bull. 1991, 39,
3100–3102.
Supplementary data
20. Horaguchi, T.; Hosokawa, N.; Tanemura, K.; Suzuki, T. J. Heterocycl. Chem. 2002,
39, 61–67.
21. Hershfield, R.; Schmir, G. L. J. Am. Chem. Soc. 1973, 95, 7359–7369.
22. Wang, B.; Zheng, A. Chem. Pharm. Bull. 1997, 45, 715–718.
23. Cisse, L.; Tine, A.; Aaron, J. J. Bull. Chem. Soc. Ethiop. 1996, 10, 33–38.
Supplementary data (materials and instruments, and synthesis
of DHCIN) associated with this article can be found, in the online
version, at doi:10.1016/j.tetlet.2009.06.031.