Donor-acceptor biaryl lactones: PH induced molecular switches with intramolecular charge transfer modulation

Article abstract of DOI:10.1016/j.tetlet.2012.09.016

The physical properties of biaryl-containing compounds are known to be highly dependent on molecular geometry. We report the syntheses and fundamental spectroscopic study of two donor-acceptor biaryl lactone (6H-benzo[c]chromen-6- one) pH-driven switches.

Full text of DOI:10.1016/j.tetlet.2012.09.016

Tetrahedron Letters 53 (2012) 6245–6249
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Donor–acceptor biaryl lactones: pH induced molecular switches with
intramolecular charge transfer modulation
⇑
Erik J. Carlson, Asia Marie S. Riel, Bart J. Dahl
University of Wisconsin-Eau Claire, 105 Garfield Ave., Department of Chemistry, Eau Claire, WI 54702, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
The physical properties of biaryl-containing compounds are known to be highly dependent on molecular
geometry. We report the syntheses and fundamental spectroscopic study of two donor–acceptor biaryl
lactone (6H-benzo[c]chromen-6-one) pH-driven switches. These compounds have been determined to
rapidly and efficiently switch between two geometric states upon cycling of acidic or basic stimuli.
The planar lactone state exhibits enhanced intramolecular charge transfer (ICT) between the donor
and acceptor units which is instantly attenuated upon addition of basic stimuli. The resulting lactone
cleavage enables aryl–aryl bond rotation thus decreasing the extent of conjugation between the rings.
Each state is readily identifiable by the significant changes that occur in their respective UV–vis spectra
and luminescent character, indicative of the facile modulation of extended conjugation by pH.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 13 August 2012
Revised 4 September 2012
Accepted 5 September 2012
Available online 13 September 2012
Keywords:
Molecular switch
Intramolecular charge transfer
Biaryl
Spectroscopic properties, such as electronic excitation, emission
benzo[c]chromen-6-one switches (1 and 2) and have determined
that the lactone unit can be instantaneously cleaved and re-
formed following addition of basic and acidic stimuli, respec-
tively, leading to rapid modulation of molecular geometry. The
extent of ICT is directly correlated to the planar geometry of
the lactonized state and the non-planar geometry of the ring-
opened state and is readily probed with UV–vis and fluorescence
spectroscopy. Many elegant pH-driven switches of molecular con-
formation, configuration, and complexation have been reported.6
However, most synthetic molecules capable of pH-induced ICT
modulation operate by functional group protonation and deproto-
nation and not by changes in molecular geometries.7 Biaryl
lactones 1 and 2 are pH-driven switches of both molecular geom-
etry and ICT.
1
and non-linear optics, and physical properties, such as conduc-
2
tance, of biaryl-containing molecules are directly correlated with
the geometry of the aryl–aryl bond. Efficient pi orbital overlap oc-
curs when the biaryl moiety can adopt a planar conformation,
resulting in facile electron transport between the arene rings.
Biphenyl is known to have a dihedral angle of 30–40° in solution,
thus maximizing conjugation while minimizing steric interactions
3
between ortho hydrogens. Biaryls capable of controllable modula-
tion in their geometries and degree of conjugation could therefore
ultimately become useful when applied to sensing, optical switch-
ing, molecular logic devices, or molecular electronic technologies.
A few studies have been reported describing reversible biaryl dihe-
dral angle restriction as a strategy for molecular switching of the
degree of extended conjugation but, to the author’s knowledge,
none have employed pH as the stimulus.1
8
Biaryl lactone 1 was prepared via aromatic nitration and
a,1d,4
esterification of 3 to afford 4 (Scheme 1). This was followed by
9
Biaryl lactones have been shown to be capable of unidirec-
tional aryl–aryl bond rotation via sequential addition of chemical
microwave-mediated Suzuki coupling with boronic acid 6.
1
0
Lactonization of 7 with boron tribomide achieved 1 while seren-
dipitously leaving the p-methoxy unit unchanged. Biaryl lactone 2
5
stimuli. The lactone unit is the key feature in these systems: it
can be cleaved, modified, and reformed under specific reaction
conditions. These studies have not, however, explored the funda-
mental nature of how simple biaryl lactone cleavage and reforma-
tion could rapidly and reversibly affect through-ring conjugation
and intramolecular charge transfer (ICT). To this end, we have
was synthesized by reducing the nitro unit on 4 with SnCl
2
to the
aniline and subsequent iodination. The iodoarene then underwent
1
1
selective Pd-catalyzed cyanation exclusively at the iodo-substi-
tuted carbon to afford 5. Microwave-mediated Suzuki coupling of
5 with 6 was unsuccessful, resulting in hydration of the cyano unit.
However, Suzuki coupling under more standard conditions and
0
synthesized two new 4,4 -disubstituted donor–acceptor 6H-
1
0
lactonization with boron tribromide resulted in lactone 2, also
leaving the p-methoxy unit unchanged.
⇑
Corresponding author. Tel.: +1 715 836 4179; fax: +1 715 836 4979.
E-mail address: dahlbj@uwec.edu (B.J. Dahl).
Lactones 1 and 2 were studied to determine the ideal conditions
for rapid pH-driven switching in the same reaction pot (Scheme 2).
0
040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.09.016

6
246
E. J. Carlson et al. / Tetrahedron Letters 53 (2012) 6245–6249
Scheme 1. Syntheses of biaryl lactone switches 1 and 2.
Cleavage of the lactone unit in other 6H-benzo[c]chromen-6-one
derivatives in base and formation of the lactone in acid is known
but it has not been reported to occur in the same pot.12 We antic-
ipated some difficulty due to the expected differences in solubility
of the two states. Initial attempts to switch 1 or 2 under multiple
biphasic conditions were unsuccessful. However, either lactone
9 remaining in the reaction was negligible (less than 1% of the ini-
tial mass). Acidification of the aqueous-soluble 1a, 2a, and 9a to
achieve the protonated forms for characterization without com-
plete lactonization back to 1, 2, or 9 proved to be difficult, as was
also indicated in other studies of analogous compounds.5
Therefore, to unambiguously identify the aqueous-soluble ring-
opened state (1a, 2a, and 9a), the alkaline aqueous layer was re-
acted with dimethylsulfate and tetrabutylammonium bromide
(TBAB). Analysis revealed that 1, 2, and 9 had been completely con-
verted into 7, 8, and 10, supporting the presence of the ring-opened
states (1a, 2a, or 9a) in the alkaline media.
a,12a
3
dissolved in 1:2 CH OH–THF resulted in instantaneous ring-cleav-
age upon addition of 5% aq NaOH as the stimulus, readily observa-
ble by a visible color change (yellow to red for 1 to 1a and colorless
to yellow for 2 to 2a). Similarly, the use of tetrabutylammonium
hydroxide (TBA-OH) as the stimulus also resulted in instantaneous
The biaryl lactones were examined by UV–vis spectroscopy15 to
determine the effect that pH-driven switching would have on con-
jugation through the biaryl unit (Fig. 1). Donor–acceptor 1 and 2
3
ring-opening of 1 or 2 dissolved in CH CN. Rapid lactonization of
1
a or 2a back to 1 or 2 was achieved upon addition of a second
stimulus, aqueous HCl or trifluoroacetic acid (TFA), as easily ob-
served by a return to the original solution color. The switching pro-
3
dissolved in CH CN both exhibited intense ICT bands at 356 nm
1
ꢀ1
ꢀ1
ꢀ1
ꢀ1
cess could also be readily monitored with H NMR spectroscopy by
(e = 172185 M cm ) and 317 nm (e = 36686 M cm ), respec-
observing the relative upfield shifts of the protons resonating in
the aromatic region as 1 and 2 was converted into 1a and 2a.
tively. A significant attenuation of the ICT band and a correspond-
ing bathochromic shift was immediately observed upon addition of
TBA-OH to afford non-planar 1a and 2a. The observed red-shift of
the dianionic ring-opened states (1a and 2a) was determined to be
due to the ortho-phenoxide generated upon lactone cleavage being
a stronger electron donor than the para-methoxy group present in
the ring-closed state (1 and 2). This was supported by examination
of the ring-opened analogs 7 and 8, both containing methoxy units
in place of phenoxides, and noting the hypsochromic shift relative
to 1a and 2a. However, the large decrease in the charge transfer
band intensity of ring-opened states (1a and 2a) and their methyl-
ated analogs (7 and 8) compared to the ring-closed states (1 and 2)
is direct evidence of the attenuation of conjugation between the
1
3
Product analysis after one switching cycle revealed that 1 and 2 were
the only species present, each recovered in a near-quantitative
yield. Unsubstituted biaryl lactone 9 was also prepared from 9-
1
4
fluorenone to directly compare with donor–acceptor lactones 1
and 2. All three compounds (1, 2, and 9) were observed to rapidly
and efficiently cycle between their open and closed states upon
each consecutive addition of acid or base.
To further characterize the pH-driven switching processes, 1, 2,
or 9 was dissolved in 1:2 CH
immediately partitioned into CH
CH Cl layer was evaporated to reveal that the amount of 1, 2, or
3
OH–THF, 5% aq NaOH was added, and
2
Cl and water (Scheme 2). The
2
2
2

E. J. Carlson et al. / Tetrahedron Letters 53 (2012) 6245–6249
6247
Scheme 2. pH-Driven switching studies. Reagents: (a) CH
3
CN and TBA-OH or 1:2
Cl
CH OH–THF and aq NaOH; (b) aq HCl or TFA; (c) Me SO , TBAB, CH
3
2
4
2
2
.
two rings in the ring-opened state. Additionally, unsubstituted 9
exhibited comparatively small changes in its spectra upon pH-
driven ring-opening to 9a, illustrating the significance of the donor
and acceptor units. Compounds 1 and 2 are therefore capable of
rapid and reversible pH-driven ICT modulation which directly cor-
responds to changes in their molecular geometries.
The switching process was also examined at various pH values
1
5
(
Fig. 2). To analyze ring-opening, aq. NaOH at varying pH was
added to samples of 1 or 2 dissolved in 1:2 CH OH–THF. Each reac-
tion mixture was extracted with CH Cl and analyzed by UV–vis to
3
2
2
determine the relative amount of 1 or 2 remaining after addition of
base at differing pH. For both 1 and 2 very little ring-opening oc-
curred when the pH is < 12. However, addition of aq. NaOH with
pH >12 resulted in all of 1 or 2 ring-opening to 1a or 2a. To analyze
ring-closing, 5% aq NaOH was added in excess to 1 or 2 dissolved in
Figure 1. Electronic absorption spectra of 1, 2, and 9, their corresponding ring-
opened products 1a, 2a, and 9a, and the methyl-trapped ring-opened species 7, 8,
1
:2 CH
each aliquot acidified with aq HCl to a specific pH. Each sample
was extracted with CH Cl and analyzed by UV–vis to determine
3
OH–THF. The aqueous layer was separated, divided, and
and 10, at the noted concentrations in CH
3
CN. Spectra of 1a, 2a, and 9a were taken
CN.
2
2
upon addition of TBA-OH to 1, 2, and 9, at the noted concentrations in CH
3
the relative amount of 1 or 2 afforded by ring-closing in acid at dif-
fering pH. It was found that, for both 1 and 2, very little conversion
occurred when the pH of the acid is >5. However, addition of aq
HCl with pH values <5 resulted in all of 1a or 2a ring-closing back
to 1 or 2.
neither compound exhibited fluorescence at the previous excita-
tion wavelength. The luminescence properties of 1 and 2 can there-
fore be rapidly modulated via pH-driven switching. Analog 9
without donor or acceptor units did not visibly luminesce.
Some compounds containing the 6H-benzo[c]chromen-6-one
unit have been reported to be brightly fluorescent.16 The lumines-
cence of planar lactone switches 1 and 2 was therefore examined
and directly compared to the ring-opened states 1a and 2a. Solu-
tions of lactone 1 and 2 exhibit faint green17 and bright blue lumi-
nescence, respectively, when irradiated with a UV lamp (Fig. 3).
However, the luminescence is immediately attenuated upon addi-
tion of TBA-OH to 1 or 2 generating 1a or 2a. The luminescence
could be rapidly regenerated upon addition of TFA. The compounds
were further analyzed using fluorescence spectroscopy.1 The cya-
no-containing 2 emits at 420 nm (kex = 316 nm) and nitro-contain-
ing 1 emits at 515 nm (kex = 370 nm). After addition of TBA-OH,
In conclusion, donor–acceptor biaryl lactone switches 1 and 2
have been synthesized and are reversibly, rapidly, and efficiently
switched upon changes in pH resulting in a geometry modulation.
The increased degree of through-ring conjugation in the ring
closed state leads to enhanced ICT and luminescence. The de-
creased degree of through-ring conjugation in the ring-opened
state leads to attenuated ICT and a lack of luminescence. The
6H-benzo[c]chromen-6-one moiety has been shown to be an
attractive molecular switch prototype and further studies are
planned to explore the effect of functional groups, tethering units,
8

6
248
E. J. Carlson et al. / Tetrahedron Letters 53 (2012) 6245–6249
Figure 2. UV–Vis spectra of CH
2
Cl
2
indicating the relative amounts of 1 or 2 present extractions after treatment at various pH.
Supplementary data
Supplementary data (Details of spectroscopic studies, experi-
mental procedures, and characterization data for all new com-
pounds) associated with this article can be found, in the online
version, at http://dx.doi.org/10.1016/j.tetlet.2012.09.016.
References and notes
1.
For examples see: (a) Fahrni, C. J.; Cody, J. Tetrahedron 2004, 60, 11099–11107;
b) Sherwood, D. W.; Calvin, M. J. Am. Chem. Soc. 1942, 64, 1350–1353; (c)
(
Berlman, I. Handbook of Fluorescence Spectra of Aromatic Molecules; Academic
Press: New York, 1971; (d) McFarland, S. A.; Finney, N. S. J. Am. Chem. Soc. 2001,
1
23, 120–121; (e) Effenberger, F.; Agster, W.; Fischer, P.; Jogun, K. H.;
Stezowski, J. J.; Daltrozzo, E.; Kollmanssberger-von Nell, G. J. Org. Chem. 1983,
8, 4649–4658; (f) Cheng, L.-T.; Tam, W.; Marder, S. R.; Stiegman, A. E.; Rikken,
4
G.; Spangler, C. W. J. Phys. Chem. 1991, 95, 10643–10652.
Figure 3. Photograph of, from left to right, samples of 1, 1a, 2, and 2a dissolved in
CH CN irradiated under a UV lamp. Compounds 1a and 2a were generated via
addition of TBA-OH to 1 and 2, respectively.
2
.
.
(a) Venkataraman, L.; Klare, J. E.; Nuckolls, C.; Hybertsen, M. S.; Steigerwald, M.
L. Nature 2006, 442, 904–907; (b) Mishchenko, A.; Vonlanthen, D.; Meded, V.;
Burkle, M.; Li, C.; Pobelov, I. V.; Bagrets, A.; Viljas, J. K.; Pauly, F.; Evers, F.;
Mayor, M.; Wandlowski, T. Nano Lett. 2010, 10, 156–163; (c) Mischenko, A.;
Zotti, L. A.; Vonlanthen, D.; Burkle, M.; Pauly, F.; Cuevas, J. C.; Mayor, M.;
Wandlowski, T. J. Am. Chem. Soc. 2011, 133, 184–187; (d) Sakano, T.;
Higashiguchi, K.; Matsuda, K. Chem. Commun. 2011, 47, 8427–8429.
Akiyama, M.; Watanabe, T. J. Phys. Chem. 1986, 90, 1752–1755. and references
therein.
3
and conjugation length on switching capabilities, ICT, and
fluorescence.
3
Acknowledgments
4. (a) Metcalfe, R. A.; Dodsworth, E. S.; Lever, A. B. P.; Pietro, W. P.; Stufkens, D. J.
Inorg. Chem. 1993, 32, 3581–3582; (b) Llarena, I.; Benniston, A. C.; Izzet, G.;
Rewinska, D. B.; Harrington, R. W.; Clegg, W. Tetrahedron Lett. 2006, 47, 9135–
Acknowledgment is made to the donors of the American Chem-
ical Society Petroleum Research Fund (ACS PRF 51259-UNI1) for
support of this research. We are also grateful for the Student
Blugold Commitment Differential Tuition funds through the Uni-
versity of Wisconsin-Eau Claire Faculty/Student Research Collabo-
ration Grants program for financial support.
9138; (c) Benniston, A. C.; Harriman, A.; Patel, P. V.; Sams, C. A. Eur. J. Org. Chem.
2005, 4680–4686.
5. (a) Lin, Y.; Dahl, B. J.; Branchaud, B. P. Tetrahedron Lett. 2005, 46, 8359–8362;
(
8
b) Fletcher, S. P.; Dumur, F.; Pollard, M. M.; Feringa, B. L. Science 2005, 310, 80–
2; (c) Dahl, B. J.; Branchaud, B. P. Org. Lett. 2006, 8, 5841–5845.
6.
Several recent examples include: (a) Su, X.; Aprahamian, I. Org. Lett. 2011, 13,
30–33; (b) Landge, S. M.; Aprahamian, I. J. Am. Chem. Soc. 2009, 131, 18269–

E. J. Carlson et al. / Tetrahedron Letters 53 (2012) 6245–6249
8271; (c) Richmond, C. J.; Parenty, A. D. C.; Song, Y.-F.; Cooke, G.; Cronin, L. J. 9. Leadbeater, N. E.; Marco, M. J. Org. Chem. 2003, 68, 888–892.
6249
1
Am. Chem. Soc. 2008, 130, 13059–13065; (d) Leblond, G.; Gao, H.; Petitjean, A.;
Leroux, J.-C. J. Am. Chem. Soc. 2010, 132, 8544–8545; (e) Cheng, K.-W.; Lai, C.-C.;
Chiang, P.-T.; Chiu, S.-H. Chem. Commun. 2006, 2854–2856; (f) Coutrot, F.;
Romuald, C.; Busseron, E. Org. Lett. 2008, 10, 3741–3744; (g) Shiraishi, Y.;
Tokitoh, Y.; Nishimura, H.; Hirai, T. Org. Lett. 2005, 7, 2611–2614; (h) Brazdova,
B.; Zhang, N.; Samoshin, V. V.; Guo, X. Chem. Commun. 2008, 4774–4776; (i)
Jones, I. M.; Lingard, H.; Hamilton, A. D. Angew. Chem., Int. Ed. 2011, 50, 12569–
10. Kim, I.; Kim, T.-H.; Kang, Y.; Lim, Y.-B. Tetrahedron Lett. 2006, 47, 8689–8692.
11. Sundermeier, M.; Zapf, A.; Beller, M. Eur. J. Inorg. Chem. 2003, 3513–3526.
12. (a) Caswell, M.; Schmir, G. L. J. Am. Chem. Soc. 1980, 102, 4815–4821; (b) Alam,
A.; Tsuboi, S. Tetrahedron 2007, 63, 10454–10465; (c) Tremblay, M. S.; Sames,
D. A. Org. Lett. 2005, 7, 2417–2420; (d) Quideau, S.; Feldman, K. S. J. Org. Chem.
1997, 62, 8809–8813.
13. See the Supplementary data for details and NMR spectra.
14. Mehta, G.; Pandey, P. N. Synthesis 1975, 6, 404–405.
1
2571. and references therein.
7
.
.
(a) Maus, M.; Rurack, K. New J. Chem. 2000, 24, 677–686; (b) Vaidya, S.; Schmell,
R. H. New J. Chem. 2012, 36, 52–55; (c) Shilova, E. A.; Heynderickx, A.; Siri, O. J.
Org. Chem. 2010, 75, 1855–1861; (d) Yukruk, F.; Akkaya, E. U. Tetrahedron Lett.
15. See the Supplementary data for full details of UV–vis spectroscopy
characterization.
16. Appel, B.; Saleh, N. N. R.; Langer, P. Chem. Eur. J. 2006, 12, 1221–1236.
17. Nitroarenes are well known to quench fluorescence. See for example: Seely, G.
R. J. Phys. Chem. 1969, 73, 125–129.
2
005, 46, 5931–5933; (e) Kim, S.-H.; Gwon, S.-Y.; Bae, J.-S.; Son, Y.-A.
Spectrochim. Acta A 2011, 78, 234–237; (f) Wang, Z.; Zheng, G.; Lu, P. Org.
Lett. 2005, 7, 3669–3672; (g) Chen, B.; Peng, M.-L.; Wu, L.-Z.; Zhang, L.-P.; Tung,
C.-H. Photochem. Photobiol. Sci. 2006, 5, 943–947; (h) Ji, S.; Yang, J.; Yang, Q.;
Liu, S.; Chen, M.; Zhao, J. J. Org. Chem. 2009, 74, 4855–4865.
Zhi, L.; Ringgenberg, J. D.; Edwards, J. P.; Tegley, C. M.; West, S. J.; Pio, B.;
Motamedi, M.; Jones, T. K.; Marschke, K. B.; Mais, D. E.; Schrader, W. T. Bioorg.
Med. Chem. Lett. 2003, 13, 2075–2078.
18. See the Supplementary data for full experimental details as well as excitation
and emission spectra of 1 and 2.
8