Synthesis of coumarin/pyrrole-fused heterocycles and their photochemical and redox-switching properties

Article abstract of DOI:10.1021/ol401138q

Two coumarin/pyrrole-fused heterocycles were synthesized to investigate their photochemical and redox-switching properties. Photooxidation of the colorless diphenyl-substituted pyrrolocoumarin resulted in a distinct change to red and a sharp decrease in f

Full text of DOI:10.1021/ol401138q

ORGANIC
LETTERS
2013
Vol. 15, No. 11
2802–2805
Synthesis of Coumarin/Pyrrole-Fused
Heterocycles and Their Photochemical
and Redox-Switching Properties
Chi-Hui Lin and Ding-Yah Yang*
Department of Chemistry, Tunghai University, No. 181, Section 3, Taichung Port Road,
Taichung City 40704, Taiwan, Republic of China
yang@thu.edu.tw
Received April 23, 2013
ABSTRACT
Two coumarin/pyrrole-fused heterocycles were synthesized to investigate their photochemical and redox-switching properties. Photooxidation of
the colorless diphenyl-substituted pyrrolocoumarin resulted in a distinct change to red and a sharp decrease in fluorescence intensity. The
photooxidized product can be swiftly reverted to the original form by NaCNBH3 reduction or hydrogenation.
Coumarin and its derivatives represent an important
class of heterocycles that have wide applications in the
areas of medicinal chemistry1 and functional materials.2
When coumarins are fused with other molecular scaffolds,
the resulting compounds may generally exhibit promising
or even unprecedented properties. For instance, coumarin/
phenanthridine-fused heterocycles have been found to pos-
sess unique negative thermochromic properties,3 whereas
coumarin/pyran-fused heterocycles have been reported to
exhibit molecular switching properties.4 Since some pyrrole
derivatives have been documented to be light-sensitive and
are prone to undergo oxidation upon UV irradiation,5 we
speculate that coumarin/pyrrole-fused heterocycles may also
reveal intriguing functional properties. In our continuing
efforts to develop novel coumarin-based functional materials,
we report the synthesis of two 7-dimethylaminocoumarin/
pyrrole-fused derivatives and subsequent evaluation of their
photochemical and redox-switching properties. Our studies
indicate that both compounds are highly sensitive to light,
and one may potentially function as an organic redox switch
with color change and emission variation as two output
properties.
Scheme 1 shows the preparation of the pyrrolocoumar-
ins 1 and 2. The microwave-promoted coupling of 3-acyl-
coumarins 36 or 47 with 1-amino-1-phenylpropan-2-one
hydrochloride (5)8 using diisopropylethylamine (DIPEA)
as a base in dichloroethane (DCE) generated the 4-amino-
substituted coumarin 6 or 7. The subsequent refluxing 6
and 7 in the presence of a catalytic amount of p-TsOH in
methanol for 0.5 h afforded the target pyrrolocoumarins 1
and 2 almost quantitatively.
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r
10.1021/ol401138q
Published on Web 05/28/2013
2013 American Chemical Society

water to yield the 9. The subsequent [1,5]-acyl migration
from the C-2 to C-3 position of 9 furnishes the 10.11 Final
methanolysis of 10 in methanol releases the target 2. The
aforementioned mechanism is strongly supported by the
isolation and characterization of the rearranged intermedi-
ate 109 during the reaction (Figure S1 in the SI). We believe
this acid-catalyzed sequence of cyclization, dehydration, re-
arrangement, and methanolysis of 3-acyl-4-amino-substituted
coumarins may provide an alternate route to the preparation
of valuable multisubstituted pyrrole heterocycles.
Scheme 1. Preparation of Pyrrolocoumarins 1 and 2
Scheme 2. Proposed Mechanism for the Formation of 2 from 7
The molecular structures of 6, 7, 1, and 2 were verified by
1H and 13C NMR spectroscopy as well as the X-ray crystall-
ography as depicted in Figure 1.9 Note that the 1H NMR
spectra of 7 and 6 show a broad absorption peak at chemical
shifts of 13.42 and 8.57 ppm, respectively, indicating the
presence of an intramolecular H-bonding between the
carbonyl oxygen and amino hydrogen in solution. Indeed,
this H-bonding is clearly observed in the crystal data of 7
(Figure 1). Interestingly, no H-bonding between the 3-car-
bonyl oxygen and 4-amino hydrogen was found in the
crystal structure of 6. Instead, it shows that the two phenyl
groups lie parallel to each other with the distance between
With the availability of 1 and 2, their photochemical
properties and redox-switching behaviors were then inves-
tigated. Both pyrrolocoumarins were found to be highly
sensitive to light and change colors when exposed to UV light.
For instance, upon UV irradiation (352 nm, 8 W each ꢁ8),
the colorless 1 turned red within seconds. Figure 2 shows
the UVꢀvis absorbance changes of 1 in methylene chloride
prior to andafterirradiation. Withtheincreaseofexposure
time, a new broad absorption band with the peak wave-
length around 504 nm gradually emerged, along with the
appearance of three isosbestic points at 265, 299, and
387 nm. To our delight, the photogenerated product of 1
was stable enough to be isolated and characterized to be
the alcohol 11 (Scheme 3), although the photogenerated
product of 2 was not.
ꢀ
˚
them measured to be ∼3.40 A, and are nearly orthogonal to
the coumarin moiety. This observation suggests that 6
mainly exists in a stable aromatic πꢀπ stacking conforma-
tion in the solid state, presumably due to the favored crystal
packing during crystallization.10
Figure 3 depicts the crystal structure of 11,9 which
clearly reveals a disrupted aromatic pyrrole ring along
with a tertiary alcohol at the C-3 position. To explore the
roleof the 7-aminogroupinthisphotooxidation, 12, which
lacks the 7-dimethylamino group on the coumarin moiety,
(9) Crystallographic data (excluding structure factors) for 1, 2, 6, 7,
10, and 11 have been deposited with the Cambridge Crystallographic
Data Centre as supplementary publication number CCDC-930377, -
930378, -930379, -930380, -930381, and -930382, respectively. These
data can be obtained free of charge via www.ccdc.cam.ac.uk/data_re-
quest/cif, or by emailing data_request@ccdc.cam.ac.uk, or by contact-
ing The Cambridge Crystallographic Data Centre, 12, Union Road,
Cambridge CB2 1EZ, UK; fax: þ44 1223 336033.
Figure 1. ORTEP crystal structures of 6, 7, 1, and 2.
Scheme 2 depicts the proposed mechanism for the
formation of 2 from 7. It begins with acid-catalyzed
intramolecular cyclization of 7 to give the tertiary alcohol
8, which isfollowedby 1,4-elimination toloseamoleculeof
(10) Lin, C. H.; Chuang, R. R.; Kuo, P. Y.; Yang, D. Y. Tetrahedron
Lett. 2013, 54, 2431–2434.
(11) Tsuge, O.; Uneo, K.; Oe, K. Chem. Lett. 1979, 11, 1407–1410.
(12) Joshi, S. D.; Sakhardande, V. D.; Seshadri, S. Indian J. Chem.,
Sect. B 1984, 23, 206–208.
Org. Lett., Vol. 15, No. 11, 2013
2803

Figure 3. ORTEP crystal structure of 11.
Scheme 4. Photooxidation of 12
Figure 2. Absorption spectra of 1 (3.1 ꢁ 10ꢀ5 M in CH2Cl2)
obtained with different exposure times (352 nm), 0 to 60 s, in
increments of 10 s.
Scheme 3. Redox Switching between 1 and 11
was prepared12 and subjectedto irradiation under thesame
conditions as those for 1. No photooxidation product was
observed even when 12 was under prolonged irradiation
(Scheme 4). The fact that 12 is light-insensitive and does
not respond to UV light suggests that the 7-dimethylamino
group of 1 plays a crucial role in its photochemical proper-
ties, presumably owing to the amine’s strong electron-
donating properties. This assumption was supported by
the cyclic voltammetry (CV) of 1and 12 (Figure S5 in the SI).
The CV data indicate that the presence of the dimethylamino
group on the 7-position of the coumarin ring of 1 drastically
decreases the oxidation potential of the pyrrole ring from
þ1.338 to þ0.769 V, which renders 1susceptible to oxidation
upon UV irradiation.
Figure 4. Fluorescence spectra of 1 (2.5 ꢁ 10ꢀ6 M in CH2Cl2)
obtained with different exposure times (352 nm), 0 to 21 s, in
increments of 3 s.
In addition to color change, 1 also exhibited a second
output property upon UV irradiation, that is, emission
variation. Figure 4 shows the time-dependent fluorescence
spectra of 1 obtained with different exposure times (352 nm).
While 1 was highly fluorescent in CH2Cl2 (λmax = 410 nm,
Φf = 0.65), the fluorescence intensity at 410 nm decreased
substantially with the increase in exposure time. The resulting
oxidized 11 is essentially nonfluorescent in CH2Cl2 (Φf = 0.03)
with up to a 21-fold decrease in fluorescence quantum yield
after photooxidation. The quenching of the intrinsic 7-di-
methylaminocoumarin fluorescence in 11 is probably caused
by the efficient electronic coupling between the 7-dimethyla-
minocoumarin donor and the N-benzylideneimine acceptor.
The photogenerated compound 11 can be swiftly re-
verted to the original 1 when treated with reducing agents
such as sodium cyanoborohydride (NaCNBH3) or bub-
bled with H2 under acidic conditions (Scheme 3). The
reverse reaction mechanism apparently involves imine
reduction/hydrogenation and is followed by acid-cata-
lyzed dehydration to reconstitute the pyrrole ring. While
hydrogenation is more atom-economical (both H-atoms
are incorporated into the product) than NaCNBH3 reduc-
tion, the Pd/C catalyst needs to be removed from the
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Org. Lett., Vol. 15, No. 11, 2013

Scheme 5. Preparation of Pd/Fe3O4 Magnetic Nanoparticles
system via either filtration or centrifugation before entering
the next redox-switching cycle. In an effort to avoid this
repeated filtration/centrifugation process, the metal catalyst
Pd/C was replaced with the Pd-functionalized Fe3O4 mag-
netic nanoparticles (Pd-MNPs), which can be magnetically
pulled down from the solution with an external magnet. The
Pd/Fe3O4 MNPs13 were readily accessed by the coupling of
Na2PdCl4 with the commercially available Fe3O4 nano-
particles in aqueous NaOH solution and was followed by
reduction with NaBH4 in methanol, as depicted in Scheme 5.
The Pd-grafted magnetic materials were further char-
acterized by XRD spectroscopy (Figure S6 in the SI).
Figure 5 shows the time-dependent absorption spectra of
11 in CH2Cl2 with different exposure times to the bubbling
H2 gas in the presence of catalytic amounts of Pd-MNPs
and formic acid. Delightfully, the red 11 turned colorless
again with the reappearance of the 354 nm absorption
band, which is characteristic for 1. The reversible switching
process between 1 and 11 by UV irradiation and hydro-
genation was repeated for 10 cycles without significant
changes in the UVꢀvis spectra (Figure S8 in the SI). Note
thatthePd-MNPswerereused inthenextcyclewithalmost
consistent catalytic activity. When Pd-MNPs were replaced
with the unfunctionalized MNPs, no reversible switching
between 1 and 11 was observed (Figure S9 in the SI). The
result suggests that reduction of 11 back to 1 was indeed
catalyzed by Pd attached onto the MNPs.
Figure 5. Absorption spectra of 11 (1.5 ꢁ 10ꢀ5 M in CH2Cl2)
obtained with different exposure times to bubbling H2 gas,
HCO2H (1.0 ꢁ 10ꢀ6 M), and Pd-MNPs (2 mg), 0 to 2 m, in
increments of 0.5 m.
“near-perfect” redox-switching reaction, as it proceeds
through a highly atom-economical and almost waste-free
manner (the only byproduct generated is water).
In summary, two new pyrrolocoumarins 1 and 2 were
synthesized and characterized via acid-catalyzed intramo-
lecular cyclization of 6 and 7, respectively. Both com-
pounds were found to be highly light-sensitive and
change colors upon UV irradiation. We have demon-
strated that the reversible switching between the pyrrolo-
coumarin 1 and the tertiary alcohol 11 can be realized by
utilizing photooxidation and chemical reduction as two
external stimuli with two easily detectable output proper-
ties, that is, color change and emission variation. Further
photochemical and redox-switching studies on other re-
lated pyrrolocoumarin systems are currently in progress.
Our studies indicate that the pyrrolocoumarin 1 and the
tertiary alcohol 11 are interchangeable and can be con-
verted from one to the other using UV light and H2 as two
external stimuli with two discernible output properties. In
this bistable redox-switching system, O2 is employed as the
oxidizing agent and H2 as the reducing agent. Since the
former is an ultimate oxidant, as it is virtually unlimited
and free, and the latter is an ideal reductant with the smallest
molecular weight and generates no waste, we believe that the
interconversion between 1 and 11 could be considered as a
Acknowledgment. We thank the National Science
Council of the Republic of China, Taiwan, for financially
supporting this research under Contract No. NSC 100-2113-
M-029-005-MY2.
Supporting Information Available. Synthesis of 1, 2, 6,
7, and 12; experimental details; additional spectra; and
X-ray crystal structure details for 1, 2, 6, 7, 10, and 11
(CIF). This material is available free of charge via the
Internet at http://pubs.acs.org.
(13) Liu, J. M.; Peng, X. G.; Sun, W.; Zhao, Y. W.; Xia, C. G. Org.
Lett. 2008, 10, 3933–3936.
The authors declare no competing financial interest.
Org. Lett., Vol. 15, No. 11, 2013
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