Structural effects on the ground and excited-state properties of photoswitchable hydrogen-bonding receptors

Article abstract of DOI:10.1021/jo061528a

The ground- and excited-state properties of a series of photochromic barbiturate receptors (N,N′-bis{6-[ω-(anthracen-9-yloxy) alkanoylamino]pyridin-2-yl}-5-t-butyl-isophthalamide, Tn), in which anthracene chromophores are tethered via (CH₂)

Full text of DOI:10.1021/jo061528a

Structural Effects on the Ground and Excited-state Properties of
Photoswitchable Hydrogen-Bonding Receptors
Yann Molard,† Dario M. Bassani,*,‡ Jean-Pierre Desvergne,‡ Nina Moran,§ and
James H. R. Tucker*,§
U.M.R. 6226 Sciences Chimiques de Rennes, UniVersity Rennes 1, 35042 Rennes, France,
LCOO CNRS UMR 5802, UniVersity Bordeaux 1, 33405 Talence, France, and School of Chemistry,
UniVersity of Birmingham, Edgbaston, B15 2TT Birmingham, United Kingdom
d.bassani@lcoo.u-bordeaux1.fr; j.tucker@bham.ac.uk.
ReceiVed July 24, 2006
The ground- and excited-state properties of a series of photochromic barbiturate receptors (N,N′-bis{6-
[ω-(anthracen-9-yloxy)alkanoylamino]pyridin-2-yl}-5-t-butyl-isophthalamide, Tn), in which anthracene
chromophores are tethered via (CH2)n (n ) 1, 3-6) polymethylene linkers to the H-bond receptor moiety,
are described. In these systems, the thermally reversible [4π + 4π] photodimerization of the anthracenes
yields macrocyclic receptors (TnC) that possess significantly reduced affinity toward barbital as compared
to their acyclic counterparts. The length of the tether not only determines the overall binding ability of
the cyclized receptor but also has a profound influence on the photochemical and photophysical properties
of the anthracene chromophores. The reduced mobility experienced by the covalently bound anthracenes
controls the reactivity of a fluorescent excimer that is proposed to be an intermediate in the photocyclization
process.
Introduction
switched binding is perhaps the most established.6,7 As dem-
onstrated in the early examples developed by Shinkai6a and
Ueno,7a such systems can be designed by connecting a photo-
chromic group to a supramolecular receptor. Photoswitched
binding (a form of gated photochromism8) then results if a light-
triggered structural change to the photochromic unit leads to a
There is continuing interest in the development of various
methods that enable a response to an external stimulus to control,
or be controlled by, a supramolecular binding event.1 Within
this area, switchable binding processes allow for the in situ and
noninvasive control of host-guest interactions in a reversible
manner and are directly relevant to a number of different and
topical research areas, for example, the external control of
biological2 (e.g., DNA-DNA2a or DNA-protein2b) interactions
and controllable molecular motion in interlocked structures.3
Of the several types of switchable binding processes that have
been explored in host-guest systems in the past,4,5 photo-
(2) (a) Asanuma, H.; Takarada, T.; Yoshida, T.; Tamaru, D.; Liang, X.
G.; Komiyama, M. Angew. Chem., Int. Ed. 2001, 40, 2671. (b) Woolley,
G. A.; Jaikaran, A. S. I.; Berezovski, M.; Calarco, J. P.; Krylov, S. N.;
Smart, O. S.; Kumita, J. R. Biochemistry 2006, 45, 6075 and references
therein. (c) Volgraf, M.; Gorostiza, P.; Numano, R.; Kramer, R. H.; Isacoff,
E. Y.; Trauner, D. Nat. Chem. Biol. 2006, 2, 47 and references therein.
(3) For a recent review of switchable processes in rotaxanes, see: Tian,
H.; Wang, Q. C. Chem. Soc. ReV. 2006, 35, 361.
(4) For recent examples of substrate-switched (e.g., allosteric) binding,
see: (a) Abe, H.; Masuda, N.; Waki, M.; Inouye, M. J. Am. Chem. Soc.
2005, 127, 16189 and references therein. (b) Amendola, V.; Esteban-Gomez,
D.; Fabbrizzi, L.; Licchelli, M.; Monzani, E.; Sancenon, F. Inorg. Chem.
2005, 44, 8690.
(5) For examples and reviews of redox-switched binding processes,
see: (a) Bu, J. J.; Lilienthal, N. D.; Woods, J. E.; Nohrden, C. E.; Hoang,
K. T.; Truong, D.; Smith, D. K. J. Am. Chem. Soc. 2005, 127, 6423 and
references therein. (b) Tucker, J. H. R.; Collinson, S. R. Chem. Soc. ReV.
2002, 31, 147.
* Corresponding authors. (D.M.B.) Tel: +33 540 002 827 and fax: +33
540 006 158. (J.H.R.T.) Tel: +44 121 414 4422 and fax: +44 121 414 4403.
† University Rennes 1.
‡ University Bordeaux 1.
§ University of Birmingham.
(1) (a) Lehn, J.-M. Supramolecular Chemistry, Concepts and Perspec-
tiVes; VCH: Weinheim, 1995. (b) Petitjean, A.; Kyritsakas, N.; Lehn, J.-
M. Chem.sEur. J. 2005, 11, 6818 and references therein. (c) For a review
of switchable binding processes at a surface, see: Cooke, G. Angew. Chem.,
Int. Ed. 2003, 42, 4860.
10.1021/jo061528a CCC: $33.50 © 2006 American Chemical Society
Published on Web 09/30/2006
J. Org. Chem. 2006, 71, 8523-8531
8523

Molard et al.
SCHEME 1
reversible change in guest binding affinity. Most examples of
photoswitched binding in the literature have involved metal
cation binding systems,6 where a photochromic unit (e.g.,
azobenzene) is attached to a suitable binding unit such as a
crown ether. It is somewhat surprising that the photoswitched
binding of species other than metal cations, for example, those
bound through H-bonding interactions, has been studied in less
detail.7,9
Over the past few years, we10 and others11 have studied
anthracene photochromism, which operates through a thermally
reversible [4π + 4π] photodimerization reaction, and its use in
photoswitched metal cation binding by anthracene-based recep-
tors. Here, we report our studies on a series of photoswitchable
receptors, Tn, that display marked photoswitched binding
behavior toward H-bonding neutral molecules as a result of
anthracene photodimerization (Scheme 1). The well-established
barbital receptor system developed by Hamilton12,13 was selected
as a potential binding motif, whose strong affinity for the
substrate could be modulated by conversion between an acyclic
and a macrocyclic form. Very promising preliminary results,
obtained with a trimethylene linker (T3),14 encouraged us to
investigate the influence of the size of the macrocyclic cavity.
By varying the length of the tethers connecting the anthracene
moieties to the receptor unit, variously sized macrocycles were
obtained upon photocyclization. The results obtained illustrate
the delicate balance between conformational control of excimer
reactivity and host-guest interactions and how this affects the
photochemical and photophysical properties of the acyclic
receptors.
Results
Synthesis. Scheme 2 illustrates the route taken for the
synthesis of the bis-anthracene receptors Tn (n ) 1, 3, 4, 5, 6).
Starting from commercially available anthrone 1, the corre-
sponding carboxylic acid derivatives 3n were prepared via
alkylation with ethyl-n-bromoalkanoate (K2CO3, acetone) fol-
lowed by hydrolysis of the ester group (aqueous NaOH, ethanol).
In the case of ethyl 2-bromopropanoate, elimination of HBr
proved faster than nucleophilic substitution, and the desired
carboxylic acid 32 could not be obtained. Coupling between 3n
and 2,6-diaminopyridine were performed in two steps via the
corresponding N-succinimidoyl ester intermediate (4n, prepared
by reaction with N-hydroxysuccinimide and N,N′-dicyclohexy-
lcarbodiimide in ethyl acetate at 25 °C) by reaction with an
excess of 2,6-diaminopyridine in dry CH2Cl2 and diisopropy-
lethylamine (1.5 mol. equiv). The acyclic receptors Tn were
obtained in good yield (60-75%) by amide bond formation
between the acyl chloride of the 5-tertbutyl isophthalic acid and
the 5n compounds in THF in the presence of triethylamine
followed by purification by column chromatography on alumina
(CH2Cl2/MeOH gradient).
(6) For examples and reviews of photoswitched binding of metal cations,
see: (a) Shinkai, S.; Nakaji, T.; Nishida, Y.; Ogawa, T.; Manabe, O. J.
Am. Chem. Soc. 1980, 102, 5860. (b) Kimura, K.; Sakamoto, H.; Nakamura,
M. Bull. Chem. Soc. Jpn. 2003, 76, 225. (c) Alfimov, M. V.; Fedorova, O.
A.; Gromov, S. P. J. Photochem. Photobiol., A 2003, 158, 183. (d) Bacchi,
A.; Carcelli, M.; Pelizzi, C.; Pelizzi, G.; Pelagatti, P.; Rogolino, D.; Tegoni,
M.; Viappiani, C. Inorg. Chem. 2003, 42, 5871. (e) Desvergne, J.-P.; Bouas-
Laurent, H.; Perez-Inestrosa, E.; Marsau, P.; Cotrait, M. Coord. Chem. ReV.
1999, 185-186, 257 and references therein.
(7) For photoswitched binding of charged or neutral molecules, see: (a)
Ueno, A.; Yoshimura, H.; Saka, R.; Osa, T. J. Am. Chem. Soc. 1979, 101,
2779. (b) Mulder, A.; Jukovic, A.; Huskens, J.; Reinhoudt, D. N. Org.
Biomol. Chem. 2004, 2, 1748 and references therein; (c) Hunter, C. A.;
Togrul, M.; Tomas, S. Chem. Commun. 2004, 108. (d) Goodman, A.;
Breinlinger, E.; Ober, M.; Rotello, V. M. J. Am. Chem. Soc. 2001, 123,
6213.
(8) Bouas-Laurent, H.; Du¨rr, H. Pure Appl. Chem. 2001, 73, 639.
(9) For examples and reviews of related H-bonding photoresponsive
systems, see: (a) Huang, C. H.; Bassani D. M. Eur. J. Org. Chem. 2005,
4041. (b) Yagai, S.; Karatsu, T.; Kitamura, A. Chem.sEur. J. 2005, 11,
4054. (c) Vida Pol, Y.; Suau, R.; Perez-Inestrosa, E.; Bassani, D. M. Chem.
Commun. 2004, 1270 and references therein. (d) Lucas, L. N.; van Esch,
J.; Kellogg, R. M.; Feringa, B. L. Chem. Commun. 2001, 759. (e) Vollmer,
M. S.; Clark, T. D.; Steinem, C.; Ghadiri, M. R. Angew. Chem., Int. Ed.
1999, 38, 1598. (f) Wu¨rther, F.; Rebek, J., Jr. Angew. Chem., Int. Ed. Engl.
1995, 34, 446. (g) Irie, M.; Miyatake, O.; Uchida, K.; Eriguchi, T. J. Am.
Chem. Soc. 1994, 116, 9894. (h) Bassani, D. M.; Sallenave, X.; Darcos,
V.; Desvergne, J.-P. Chem. Commun. 2001, 1446.
(10) (a) Bouas-Laurent, H.; Castellan, A.; Desvergne, J.-P.; Lapouyade,
R. Chem. Soc. ReV. 2000, 29, 43. (b) Bouas-Laurent, H.; Castellan, A.;
Desvergne, J.-P.; Lapouyade, R. Chem. Soc. ReV. 2001, 30, 248. (c)
McSkimming, G.; Tucker, J. H. R.; Bouas-Laurent, H.; Desvergne, J.-P.;
Coles, S. J.; Hursthouse, M. B.; Light, M. E. Chem.sEur. J. 2002, 8, 3331
and references therein. (d) Desvergne, J.-P.; Bitit, N.; Castellan, A.; Bouas-
Laurent, H.; Soulignac, J.-C. J. Lumin. 1987, 37, 175. (e) Ferguson, J.;
Castellan, A.; Desvergne, J.-P.; Bouas-Laurent, H. Chem. Phys. Lett. 1981,
78, 446 and references therein. (f) Marquis, D.; Desvergne, J.-P. Chem.
Phys. Lett. 1994, 230, 131.
Irradiation Studies. The conversion of receptors Tn to their
respective photoproducts TnC (n ) 3, 4, 5, 6) (Scheme 1) was
achieved by irradiating a CH2Cl2 solution of the receptor with
a high-pressure Hg lamp at λ > 330 nm (lead nitrate/sodium
bromide filter, 7 g L-1/KBr 540 g L-1).15 High dilution
(13) For examples of supramolecular assemblies based on barbiturate-
receptor interactions, see: (a) Lipkowski, P.; Bielejewska, A.; Timmerman,
P.; Reinhoudt, D. N.; Kooijman, H.; Spek, A. L. Chem. Commun. 1999,
1311. (b) Prins, L. J.; Reinhoudt, D. N.; Timmerman, P. Angew. Chem.,
Int. Ed. 2001, 40, 2382. (c) Russell, K. C.; Lehn, J. M.; Kyritsakas, N.;
DeCian, A.; Fischer, J. New J. Chem. 1998, 22, 123. (d) Berl, V.; Schmutz,
M.; Krische, M. J.; Khoury, R. G.; Lehn, J.-M. Chem.sEur. J. 2002, 8,
1227. (e) Kolomiets, E.; Lehn, J.-M. Chem. Commun. 2005, 1519. (f)
Kolomiets, E.; Buhler, E.; Candau, S. J.; Lehn, J. M. Macromolecules 2006,
39, 1173. (g) Dirksen, A.; Hahn, U.; Schwanke, F.; Nieger, M.; Reek, J. N.
H.; Voegtle, F.; De Cola, L. Chem.sEur. J. 2004, 10, 2036. (h) Dirksen,
A.; Kleverlaan, C. J.; Reek, J. N. H.; De Cola, L. J. Phys. Chem. A 2005,
109, 5248. (i) McClenaghan, N. D.; Grote, Z.; Darriet, K.; Zimine, M.;
Williams, R. M.; De Cola, L.; Bassani, D. M. Org. Lett. 2005, 7, 807. (j)
Schmittel, M.; Kalsani, V. Top. Curr. Chem. 2005, 245, 1.
(11) For other examples of photoswitched cation binding via anthracene
photodimerization, see: (a) Schafer, C.; Mattay, J. Photochem. Photobiol.
Sci. 2004, 3, 331. (b) Ikegami, M.; Ohshiro, I.; Arai, T. Chem. Commun.
2003, 1566. (c) Deng, G.; Sakaki, T.; Nakashima, K.; Shinkai, S. Chem.
Lett. 1992, 1287. For examples of photoswitched cation transport via
anthracene photodimerization, see: (a) Xu, M.; Fu, X. G.; Wu, L. Z.; Zhang,
L. P.; Tung, C. H. Phys. Chem. Chem. Phys. 2002, 4, 4030. (d) Jin, T.
Chem. Commun. 2000, 1379.
(14) Molard, Y.; Bassani, D. M.; Desvergne, J.-P.; Horton, P. N.;
Hursthouse, M. B.; Tucker, J. H. R. Angew. Chem., Int. Ed. 2005, 44, 1072.
(15) Scho¨nberg, A. PreparatiVe Organic Photochemistry; Springer-
Verlag: Berlin, 1968; p 492.
(12) (a) Chang, S.-K.; Hamilton, A. D. J. Am. Chem. Soc. 1988, 110,
1318. (b) Chang, S.-K.; Van Engen, D.; Fan, E.; Hamilton, A. D. J. Am.
Chem. Soc. 1991, 113, 7640.
8524 J. Org. Chem., Vol. 71, No. 22, 2006

Photoswitchable H-Bonding Receptors
SCHEME 2a
a Reagents: (i) Br(CH2)nCO2Et, K2CO3, acetone, reflux, 14 h; (ii) 1) NaOHaq, EtOH, reflux, 14 h; 2) H2O, HCl; (iii) NHS, DCC, ethyl acetate, 25 °C,
48 h; (iv) 2,6-diaminopyridine, DIEA, CH2Cl2, reflux, 5 days; (v) oxalyl chloride, CH2Cl2, reflux, 14 h; and (vi) triethylamine, THF, 25 °C, 14 h.
FIGURE 1. Absorption spectra of T4 and T4C in CH2Cl2. The spectra
of the other Tn and TnC compounds are similar (data not shown).
conditions (e5 × 10-4 M) and degassed solvents were used to
FIGURE 2. 1H NMR spectra of photoproducts TnC in CDCl3.
avoid intermolecular processes and oxidation of the anthracene
moieties. The reaction was followed by UV-vis spectroscopy
by monitoring the disappearance of the long-wavelength an-
thracene absorption band (350-420 nm). Once the reactions
had gone to completion, evaporation of the solutions gave the
products as white solids in quantitative yield. The UV-vis
absorption spectra of T4 and T4C measured in CH2Cl2 are
representative (Figure 1). The spectra of the remaining acyclic
and macrocyclic forms of the receptors are very similar (data
not shown). All compounds possess a band centered at ap-
proximately 300 nm, due to absorption by pyridine units, while
the acyclic forms display the characteristic shape of the first
absorption band of anthracene (mainly 1La in character) between
350 and 420 nm. In the case of T1, photoirradiation resulted in
an uncharacterized mixture of products.
1
Photoproduct Characterization by NMR. The H NMR
spectra of the isolated photoproducts are shown in Figure 2. The
appearance of a new singlet resonance at 4.43, 4.51, 4.24, and
4.36 ppm for T3C, T4C, T5C, and T6C, respectively, attributed
to the two equivalent bridgehead protons on the photodimer
subunit, confirms the occurrence of [4π + 4π] photocycload-
dition between the central rings on each anthracene unit.10
The 13C NMR spectra of each photodimer confirmed the
symmetrical nature of the products: the signals at 89.9, 90.9,
89.1, and 89.4 ppm for T3C, T4C, T5C, and T6C, respectively,
correspond to the two new quaternary carbons, whereas those
at 63.5, 65.2, 63.8, and 64.0 ppm are assigned to the two sp3
hybridized CH groups on the central ring.
J. Org. Chem, Vol. 71, No. 22, 2006 8525

Molard et al.
TABLE 1. Binding Constant Values, Kass (M-1), at 293 K
Obtained for Acyclic (Tn) and Macrocyclic (TnC) Receptors with
Barbital, 6, and DPU, 7a
barbital, 6
DPU, 7b
T3
T3C
T4
T4C
T5
T5C
T6
T6C
38000c
38b
120
5.6
160
10
76
8
33000c
450b
62000c
8300d
71000d
26000d
53
21
a Accuracy within (15%. b In CDCl3 at ca. 3.5 × 10-3 M by NMR
spectroscopy. c In CH2Cl2 at ca. 2 × 10-6 M by fluorescence spectroscopy.
d In CH2Cl2 at ca. 2.5 × 10-5 M by UV-vis spectroscopy.
FIGURE 3. Absorbance of the anthracene chromophore in T5 (ca. 4
× 10-6 M, monitored at 370 nm) upon repeated cycling through
photoinduced dimerization and thermal retrodimerization (80 °C, 8 h)
in degassed toluene.
used when the binding constant was low enough to obtain an
accurate value at NMR concentrations (K e 1000 M-1). UV-
vis and fluorescence data were analyzed using the nonlinear
regression program LETAGROP,17 whereas the NMR data were
analyzed by EQNMR.18 The resulting binding constants with 6
and 7 are displayed in Table 1. To confirm the stoichiometry
of the complexes, Job plot experiments were performed by UV-
vis spectroscopy on T5 and barbital and by 1H NMR spectros-
copy on T5C and barbital (Figure S1, Supporting Information).
The curves showed a maximum when the molar fraction ratio
reached 0.5, consistent with the formation of a 1:1 complex, as
illustrated in Figure 4.
Fatigue Studies. To examine the ability of the anthracene
photochromic system to withstand repeated cycling, degassed
toluene solutions of each acyclic receptor were successively
irradiated to form the corresponding macrocycle and then
immediately heated to regenerate the open form. To complete
thermal retrodimerization over a time scale of 24 h, it was
necessary to heat the solutions to 80 °C. The concentration of
the acyclic form after each opening process was determined by
1
examining the absorption intensity of the La band at 370 nm.
Although >90% of the acyclic form of each receptor was
recovered after each cycle, repetitive cycling leads to slow
decomposition, as shown in Figure 3 for T5 and T5C, where
the fatigue was 30% after four cycles.16
Binding Studies. For comparison purposes, the binding
properties of the receptors were focused on two neutral
molecules as guest species: barbital 6, which contains six
H-bonding sites and is fully complementary to the receptor site,
and the cyclic urea 7, which has four H-bonding sites.
The 1H NMR spectra of Tn and TnC (n ) 3 or 6) in CDCl3
before and after the addition of 1 equiv of barbital are shown
in Figure S2 (Supporting Information). With the exception of
T3C, where binding was very weak, a strong H-bonding
interaction was found, as evidenced by the large downfield shift
of the two amide signals of each receptor (e.g., +1.47 and +1.58
ppm for T3; +1.31 and +1.84 ppm for T6; and +1.21 and
+1.44 ppm for T6C).19
The only observable change to the UV-vis spectra of the
receptors upon the addition of excess barbital was a bathochro-
mic and slightly hypochromic shift in the pyridine band at 300
nm (Figure 5a), which is associated to an H-bonding interaction
involving this group. These changes were used to evaluate
binding constants. Emission spectra of the acyclic ligands were
obtained in CH2Cl2 at low concentrations (ca. 5 × 10-6 M)
(excitation at 360 nm) and exhibited a structured band with a
maximum of intensity at 420 nm assigned to the locally excited
species referred to as monomer (Figure 5b). The addition of
Binding was followed spectroscopically using 1H NMR, UV-
1
vis absorption, and fluorescence spectroscopy. H NMR was
FIGURE 4. Association of 6 and Tn receptors leads to the formation of 1:1 complexes in which 6 is held within the receptor site by six-point
H-bonding.
8526 J. Org. Chem., Vol. 71, No. 22, 2006

Photoswitchable H-Bonding Receptors
FIGURE 5. (a) Binding of barbital 6 by receptor T6 as followed by UV-vis spectroscopy in CH2Cl2 (concentration ) 2.6 × 10-5 M). The inset
shows the increase in the observed molar absorption coefficient at 315 nm upon addition of compound 6. (b) The binding of 6 by receptor T6 in
CH2Cl2 as followed by fluorescence spectroscopy. From top down: T6 at 3.7 × 10-6 M; + 0.5 equiv of 6; + 1 equiv of 6; + 2 equiv of 6; + 3
equiv of 6; + 6 equiv of 6; + 9 equiv of 6; + 17 equiv of 6; + 60 equiv of 6; + 120 equiv of 6; and + 230 equiv of 6. The inset shows the decrease
in fluorescence emission intensity at 420 nm upon addition of compound 6.
TABLE 2. Kinetic Parameters (1/λι) Obtained from Fluorescence
Emission Decay of Receptors Tn in the Absence and in the Presence
of 6a
A1
1/λ1 (ns)
A2
1/λ2 (ns)
ø2
T1
T1:6
T3
T3:6
T4
T4:6
T5
T5:6
T6
T6:6
0.89
0.71
3.9
2.6
4.3
1.9
4.8
2.4
4.9
2.2
5.7
2.2
0.08
0.33
9.6
6.0
0.98
1.09
1.19
1.03
1.04
1.03
1.01
1.07
1.15
1.16
0.73
0.99
1.33
0.98
0.45
0.06
0.04
0.06
8.3
9.7
8.3
4.1
a 20 °C in degassed CH2Cl2 at λobs ) 420 nm. Accuracy (10%.
barbital resulted in a decrease in its fluorescence intensity, which
was used to determine binding constants.
Fluorescence Lifetimes and Laser-Induced Fluorescence
Experiments. Fluorescence decay profiles were obtained in the
absence or in the presence of a large excess of 6 (ca. 1000 equiv)
in dichloromethane solutions that were degassed by three
freeze-pump-thaw cycles. The data, collected in Table 2, were
fitted to a one- or two-exponential decay and the goodness-of-
fit judged by the ø2 values (0.98-1.19) and the residual
distribution.
Time-resolved laser-induced fluorescence emission was col-
lected upon the excitation of degassed dichloromethane solutions
of Tn (ca. 5 × 10-6 M) in the absence and in the presence of
FIGURE 6. Time-resolved laser-induced fluorescence emission spectra
(corrected) of receptors Tn (ca. 5 × 10-6 M in degassed CH2Cl2)
obtained ca. 100 ns after excitation. In the absence (a) and in the
presence (b) of a large excess of 6 (ca. 5 × 10-3 M). Green: T1; gray:
T3; black: T4; red: T5; and blue: T6.
an excess amount of 6 (ca. 1000 equiv) using a frequency tripled
Nd:YAG laser (λ ) 355 nm, pulse width ) 7 ns). The emission
was collected at a right angle to the excitation beam and focused
on a spectrograph equipped with an ICCD camera. The
fluorescence emission after ca. 100 ns delay was corrected for
the response curve of the spectrograph and is shown in Figure
6.
Fluorescence and Photodimerization Quantum Yields. The
fluorescence and reaction quantum yields were determined in
degassed dichloromethane solution according to a previously
described methodology.20 Quinine sulfate in 1 N sulfuric acid
(16) No significant changes in the percentage fatigue were found from
cycling in the presence of an excess amount of barbital.
(17) (a) Sillen, L. G.; Warnqvist, B. Ark. Kemi 1968, 31, 377. (b) Sillen,
L. G.; Warnqvist, B. Ark. Kemi 1968, 31, 315. (b) Havel, J. Haltafal-Spefo
program; Mazaryle University: Brno, Moravia, Czech Republic.
(18) Hynes, M. J. J. Chem. Soc., Dalton Trans. 1993, 311.
(19) The H-bonded amide proton at 9.5 ppm in T4C underwent an upfield
shift of 0.15 ppm upon the addition of 5 equiv of barbital to indicate a
disruption of the intermolecular H-bonding interactions. Complexation of
barbital also affected the signal for the isophthaloyl proton of each receptor,
which moved downfield due to its proximity to the apical CO of guest
(e.g., +0.2, +0.1, and +0.16 ppm, respectively, for T3, T3C, and T6C).
(20) (a) Melhuish, W. H. J. Phys. Chem. 1961, 65, 229. (b) Eaton, D. E.
In Handbook of Organic Photochemistry, Vol. I; Scaiano, J. C., Ed.; CRC:
Boca Raton, FL, 1989.
J. Org. Chem, Vol. 71, No. 22, 2006 8527

Molard et al.
TABLE 3. Fluorescence Quantum Yield (Φf) and Intramolecular
Photocycloaddition Quantum Yield (Φr) in the Absence and in the
Presence of an Excess of 6 at Room Temperaturea
length maximum presumably reflects a more extended overlap
of the two anthracene moieties as a function of increasing spacer
length.
Φf
Φr
The observation of a second decay component in the excited
singlet-state lifetimes presented in Table 2 corroborates the
existence of an emissive excimer for the Tn receptors in the
presence of barbital 6. In analogy with previously investigated
intramolecular excimer-forming systems,10b the shorter decay
parameter (1.9-2.2 ns) is attributed to the emission of the locally
excited anthracene chromophore (monomer). The longer decay
component, which is accordingly attributed to excimer emission,
first increases with increasing chain length (T1, T3, and T4),
then decreases as the tether is further lengthened (T4, T5, and
T6). The optimum chain length for stabilizing the excimer is
expected to be a tradeoff between entropic contributions in
bringing the two chromophores in contact within the excited-
state lifetime of the locally excited-state and enthalpic contribu-
tions due to conformational strain in the shorter polymethylene
chains. As noted previously, excimer emission in the absence
of 6 is extremely weak, and the observed emission decay in
this case can be adequately fitted by a monoexponential decay.
With the exception of T1,22 the fluorescence lifetimes (4.3-
5.7 ns) thus reflect the decay of the locally excited anthracene
chromophores and are typical of 9-substituted anthracenes.10
The data obtained from spectroscopic investigations were
combined and used to determine binding constants with guests
6 and 7, as presented in Table 1. In the case of T5 and T6, the
binding constant with barbital was investigated by both UV-
vis and fluorescence spectroscopy (Kass ) 2.5 × 104 and 6.2 ×
104 M-1 for T5 and Kass ) 7.1 × 104 and 4.4 × 104 M-1 for
T6, as determined from absorption and fluorescence data,
respectively). Differences between binding constants determined
by these two techniques have previously been observed and
ascribed to conformational changes in the receptor during the
excited-state lifetime of chromophore.10f It is immediately
obvious from the data in Table 1 that photocyclization of the
terminal anthracene moieties has a profound effect on the host-
guest interactions of these compounds. In the case of 6, binding
to the acyclic receptors Tn is very strong, and the observed
association constants vary little with chain length. This contrasts
markedly with the cyclized receptors TnC, for whom the
association constants are very low and increase substantially
with increasing chain length. The lower affinities observed for
the macrocyclic receptors as compared to their acyclic coun-
terparts (i.e., log(Kac/Kc) > 0, Figure 7) contrast with previous
results for cyclic versus acyclic systems reported by Hamilton
in which much higher binding affinities for structurally confined
macrocyclic receptors were observed as compared to their
acyclic counterparts.12
Tn
Tn:6
Tn
Tn:6
T1
T3
T4
T5
T6
0.29
0.34
0.23
0.30
0.21
0.24
0.25
0.15
0.20
0.10
0.07
0.15
0.07
0.09
0.01
0.05
0.05
0.16
a Accuracy (15%.
was used as a secondary standard for fluorescence emission
intensity upon excitation at 366 nm (Φf ) 0.54). Photoreaction
quantum yields were determined upon excitation at 366 nm
using Aberchrome 540 as a chemical actinometer on an optical
bench equipped with a 2000 W Hg-Xe lamp and a monochro-
mator. Samples (5 × 10-5 M) were stirred during the irradiation,
and the amount of converted material was determined at 10 min
intervals by UV-vis spectroscopy using the disappearance of
1
the La band of the anthracene moieties at 370 nm until 90%
of the starting material was converted. No spontaneous recovery
of the anthracene absorption band was observed upon resting
the irradiated samples at room temperature. The results are
collected in Table 3.
Discussion
The compounds Tn are designed to bind 6 and 7 through
multiple-point H-bonding interactions. The binding sites are not
conjugated to the anthracene chromophore, and it is therefore
not surprising that only minor effects are observed in the
electronic absorption spectra of Tn upon binding of 6 or 7
(Figure 5a). In contrast, a significant quenching of the fluores-
cence emission of the anthracene moiety is observed upon
complexation of 6 (Figure 5b), indicative of more important
effects on the excited-state potential energy surface. The
decrease of the fluorescence presumably results from confor-
mational changes in the receptor moiety, which brings the two
anthracene subunits closer. Whereas this would be expected to
favor photodimerization or intramolecular self-quenching, no
concomitant increase in Φr is observed for receptors up to and
including T5 (Table 3). A plausible explanation is that the
binding of 6 favors the formation of a weakly emissive excimer
that is either not involved in the photodimerization reaction or,
more likely, whose dimerization is also chain-length dependent.
In support of this, close inspection of the steady-state fluores-
cence emission spectra presented in Figure 5b reveals a slight
increase in emission at longer wavelengths, a feature sometimes
observed in cases where a weakly fluorescent excimer is present.
To further investigate this point, time-resolved laser induced
fluorescence (LIF) was used to detect the presence of excimer
emission at longer lifetimes. In the absence of 6, the results
clearly show the presence of broad, long-wavelength emission
with very low intensity only for n ) 1, 3, and 4 with an emission
maximum located at ca. 470, 465, and 505 nm, respectively
(Figure 6a). In contrast, the addition of barbital induces stronger
excimer emission for all the acyclic receptors except n ) 1 with
maxima at 465, 495, 505, and 510 nm for n ) 3, 4, 5, and 6,
respectively (Figure 6b). The structural features that are observed
in the excimer emission are attributed to emission arising from
the locally excited chromophores.21 The increase in the wave-
This switch in behavior can be explained by examining the
solid-state crystal structures of the cyclized receptors T3C and
T5C (Figure 8).14 Photodimerization of the anthracene chro-
mophores results in the formation of HT dimers whose steric
bulk partly blocks the H-bonding cavity of the receptor moiety.
This effect is much more important in T3C due to the shorter
length of the polymethylene tether. As a result, this effectively
(21) It is also possible that the excimer is in equilibrium with the locally
excited-state.
(22) The reduced spacer length in T1 is expected to limit the mobility
of the chromophores due to restricted conformational freedom of the amide
linker. The ensuing biexponential decay may be due to the presence of
excimer fluorescence or kinetically distinct nonequilibrating locally excited-
states.
8528 J. Org. Chem., Vol. 71, No. 22, 2006

Photoswitchable H-Bonding Receptors
of each acyclic receptor in a fashion similar to 6, with the
formation of two H-bonds from the isophthalyl amide N-H
groups to the C2 carbonyl in 7. The higher binding affinities
toward 7 displayed by the receptors with shorter linkers (T3
and T4) is interesting and may be related to the proximity of
the two anthracene chromophores. The ensuing hydrophobic
cavity would enhance binding, and its effect would be expected
to decrease with increasing chain length, as is observed. Here
too, binding constants decrease substantially upon photocy-
clization of the receptor, although not as dramatically as in the
case of 6, which results in a less steep curve for 7 as depicted
in Figure 7 (dashed line).
Straightforward interpretation of the association constants
presented in Table 1 is, at least in some cases, rendered difficult
by the occurrence of intramolecular H-bonding between the two
arms of the receptor moiety. This is certainly the case for T4C,
where the unusual downfield shift of the broad singlet ascribed
to the two amide protons closest to the anthracenes25 indicates
the existence of an intramolecular H-bond (Figure 2, confirmed
as intramolecular by dilution experiments). In this compound,
it is likely that the hydrogen-bond acceptor is the oxygen atom
adjacent to the anthracene photodimer since the signal for the
photodimer bridgehead proton (at 4.51 ppm) is further downfield
FIGURE 7. Ratio of binding affinities for the open and closed form
of the receptor as a function of spacer length for compound 6 (plain
line) and compound 7 (dashed line).
than for the other macrocycles. This is also reflected in the 13
C
signal for the adjacent methylene group, which resonates at 67.8
ppm (as compared to 63.5, 64.5, and 64.7 ppm for T3C, T5C,
and T6C, respectively).
The photoinduced intramolecular photocyclization of the
anthracene chromophores occurs readily upon irradiation of
dilute degassed solutions of all but T1 acyclic receptors. In the
case of T1, photoirradiation resulted in an uncharacterized
mixture of products. This is presumably due to the small size
of the spacer link between the receptor moiety and the
anthracene groups, which hinders efficient [4π + 4π] cycload-
dition. Although photodimerization of 9-substituted anthracenes
can lead to the formation of head-to-head (HH) and head-to-
tail (HT) photodimers, only HT products were isolated upon
irradiation of T3-T6. A possible explanation is that both HT
and HH cycloadducts are formed but that the latter are thermally
labile and undergo retrocycloaddition during the course of the
irradiation. It is well-known that head-to-tail (HT) photodimers
are much more stable than their head-to-head (HH) counter-
parts10 as evidenced by the ease in which they are generally
isolated and characterized. By comparison, the corresponding
HH dimers have much shorter half-lives due to additional steric
and oxygen lone-pair repulsions that are absent in HT dimers.10
Since no fast recovery of the anthracene chromophore was
observed upon standing of the Tn receptors following irradia-
tion, it can be deduced that, if formed, HH dimers spontaneously
revert to the starting material during the course of irradiation.
With the exception of T4, the measured quantum yields for
photodimerization in the absence of 6 are identical within
experimental error (Table 3). The considerably higher propensity
of T4 toward photodimerization (Φr ) 0.15) is accompanied
by a reduction in fluorescence yield for this compound (in fact,
Φf + Φr is approximately constant for T3-T6). This suggests,
albeit indirectly, that fluorescence emission from the locally
excited state and photodimerization have as a common inter-
mediate the same S1 locally excited state and that photoreactivity
is not solely controlled by the ground-state conformational
population of the chromophores at the time of the excitation.
FIGURE 8. X-ray structures of T3C and T5C.14
prohibits simultaneous binding of the guest to both arms of the
receptor, and the observed binding constants are typical of three-
point H-bonding observed in analogous A-D-A systems.23
However, in the case of the larger macrocycles T5C and T6C,
the high binding constants indicate that the longer chains allow
simultaneous binding of the guest to both arms within the cavity
but in a suprafacial mode, facilitated by the flexibility of the
penta- or hexa-methylene chains in solution. The large upfield
shift in the CH3 resonance of the barbital ethyl group upon
complexation with T5C and T6C (-0.54 and -0.68 ppm as
compared to the complexes of 6 with their respective acyclic
forms) is indicative of the proximity of the cavity-bound guest
to the aromatic xylene units,24 as found by Hamilton for
complexes of 6 with related naphthyl macrocycles.12
The association constants between DPU, 7, and the receptors
in their acyclic and cyclic forms are also displayed in Table 3.
As expected, the binding constants are much smaller than those
with 6 due to the formation of only four H-bonds with the guest,
as evidenced by the fact that only the resonance of the two amide
protons nearest the isophthaloyl unit undergoes a significant
downfield shift upon complexation (see Supporting Information).
This information suggests that 7 is inserted within the cavity
(23) Hamilton, A. D.; Van Engen, D. J. Am. Chem. Soc. 1987, 109, 5035.
(24) In the case of T6C, the addition of barbital also had a significant
effect on the shift of other proton signals. In particular, the signals for the
OCH2 and the central photodimer CH protons moved downfield by +0.37
and +0.17 ppm, respectively.
(25) Hager, K.; Franz, A.; Hirsch, A. Chem.sEur. J. 2006, 12, 2663.
J. Org. Chem, Vol. 71, No. 22, 2006 8529

Molard et al.
Moreover, photoproduct T4C is unique among these receptors
in having strong intramolecular H-bonds (Figure 2), which may
contribute to form a pre-organized structure in the excited state
promoting photodimerization.
observed fatigue is thus a result of a small degree of degradation
of the sample due to the necessity to heat the closed forms to
relatively high temperatures for extended periods of time to
return to the open forms.
As expected, photocyclization yields are strongly affected by
the presence of 6, which binds within the cavity of the receptor
moiety located between the two anthracene chromophores. In
the case of T3-T5, the net overall effect is to reduce the
efficiency of dimerization from ca. 10 to 1-5%. This effect is
particularly dramatic for T4, which undergoes a 3-fold reduction
of its dimerization yield and is consistent with the loss of
intramolecular H-bonding in the transition-state affecting pho-
toreactivity. However, on a purely thermodynamical basis, the
significantly greater binding affinity of Tn versus TnC for 6 is
expected to reduce the overall driving force for dimerization
by providing greater stabilization for the acyclic forms as
compared to the cyclized products. Assuming that the guest is
at least partially released in the transition state toward cycliza-
tion, this would increase the activation energy for cyclization
of the acyclic receptor in the presence of 6. For T6, however,
the situation is reversed, and the efficiency of cyclization is
higher in the presence of 6 than in its absence. This result would
be consistent with the larger receptor being able to maintain its
H-bonded complex with 6 to a greater extent as photodimer-
ization proceeds, thereby stabilizing the transition state. This
observation is reminiscent of the templating effect of a barbituric
acid analogue on the intermolecular dimerization of conjuguated
alkenes possessing complementary H-bonding motifs.9 In this
system, however, the supramolecular control of the excited-
state reactivity induced by the template is further modulated
by the conformational control instilled by the polymethylene
tether linking the anthracene chromophores to the H-bonding
unit.26 Finally, it is worth noting that the accrued photoreactivity
of T6 in the presence of barbital is accompanied by a decrease
in the lifetime of the excimer as compared to T5, even though
its fluorescence emission is very similar (Figure 6b, red and
blue lines), suggesting similar excimer geometries. Taken
together, these results are consistent with the emissive excimer
located on the reaction pathway of the photocyclization reaction.
However, it cannot be completely excluded that the formation
of the fluorescent excimer observed in the LIF experiments is
in competition with the formation of a reactive but nonemissive
excimer leading to the photoproducts.
As commonly observed for anthracene cyclodimers, heating
solutions of T3-T6 in a nonpolar solvent such as toluene results
in retrocyclization to the acyclic receptors. This, of course, offers
the possibility of cycling a receptor between an acyclic form
with high affinity and a closed form with low affinity. The
degree of control that is obtained can be characterized by the
ratio of the binding constants for the acyclic and cyclized forms
toward a particular guest, which, as described previously, is
found to decrease with increasing chain length for guests 6 and
7 (Figure 7). Cycling between the closed and the open forms
of the receptors can be easily accomplished by heating the closed
receptors TnC to obtain the open forms (Tn), which can be
recyclized by irradiation. Repeated cycling was investigated
using T5 and T5C by monitoring the absorbance of the
anthracene moiety (Figure 3). It can be noted that although the
photocyclization reaction appears to be quantitative in each step,
the thermal reopening induces slight (ca. 8%) degradation. The
Conclusion
The association of a H-bonding receptor site with an
anthracene photoactive moiety is a viable approach to construct-
ing photoactive receptors for neutral molecules. The systems
are designed so that irradiation results in efficient [4π + 4π]
photodimerization of the pendant anthracenes, which induces
an important modification of the receptor binding site. These
photoreceptors possess the capability of being photoinhibited,
with binding constants that, in favorable cases, decrease by 3
orders of magnitude upon photocyclization. The photorelease
of guests upon irradiation offers interesting perspectives for
photoinduced control of molecular recognition events. The
system can be recycled by heating the closed receptors to obtain
the open forms, and future improvements could be oriented
toward reducing fatigue in this step by facilitating the thermal
retrodimerization of anthracene HT dimers. From the detailed
examination of the ground- and excited-state behavior of the
open and cyclized receptors as a function of tether size, the
complex interplay between subtle counteracting forces emerges.
The shorter tethers allow much greater discrimination to be
obtained between the binding affinities of the open and the
cyclized forms, whereas only the longest tether appears to
facilitate photodimerization in the presence of barbital. The
combination of these effects, conformational freedom of the
polymethylene linker and the supramolecular control induced
by the guest, must all be taken into account to adequately
understand the properties and limitations of these photoregulated
receptors.
Experimental Section
Spectroscopic and Photochemical Measurements. Fluores-
cence emission spectra were recorded on dilute (abs <0.2 at 366
nm) samples that were degassed by repeated freeze-pump-thaw
cycles and sealed. Fluorescence quantum yields were determined
by comparison with quinine sulfate in 1 N sulfuric acid (Φf )
0.54).20 The fluorescence decay measurements were measured using
a single-photon counting apparatus equipped with a hydrogen flash
lamp and the data were deconvoluted using the Decan 1.0
program.27 Photoreaction quantum yields were determined upon
excitation at 360 nm using Aberchrome 540 as a chemical
actinometer on an optical bench equipped with a 2000 W Hg-Xe
lamp and a monochromator. Samples (5 × 10-5 M) were stirred
during the irradiation, and the amount of converted material was
monitored at 10 min intervals by UV-vis spectroscopy by
1
measuring the disappearance of the La band of the anthracene at
370 nm until 90% of the starting material was converted. Solutions
were allowed to stand for 2 min before measurement of the UV-
vis spectrum. The quantum yield was determined from the linear
portion of the absorbance versus irradiation time graph corrected
for the absorbance by the sample. The preparative photocyclization
reactions were carried out by irradiating degassed solutions of the
receptors in dichloromethane using a Hg lamp (400 W) and a Pb-
(NO3)2/KBr (7.0 g L-1/540 g L-1) solution filter with stirring over
a period of 12 h. Fatigue studies were performed with degassed
toluene solutions of Tn (c ) 5 × 10-6 M) that were first
photocyclized by irradiation on an optical bench and then heated
(26) Castellan, A.; Desvergne, J.-P.; Bouas-Laurent, H. Chem. Phys. Lett.
1980, 76, 390.
(27) de Roek, T.; Boens, N.; Dockx. J. DECAN 1.0; Leuven, Belgium,
1991.
8530 J. Org. Chem., Vol. 71, No. 22, 2006

Photoswitchable H-Bonding Receptors
in the dark at 80 °C until no more increase in the absorption of the
anthracene band was detected (8 h). The amount of converted
material was determined every hour by UV-vis spectroscopy as
stated previously.
Binding Constants. Fluorescence Method. The receptor Tn
(solution concentration between 2 × 10-6 and 8 × 10-6 M) was
titrated with a solution of guest (typical concentration between 5
× 10-4 and 5 × 10-3 M) dissolved in the same receptor solution.
The decrease in fluorescence emission between 380 and 580 nm
was monitored as a function of guest concentration with an
excitation wavelength of 360 nm.
was concentrated under reduced pressure. The solution thus obtained
was allowed to stand at 0 °C for 4 h, which led to precipitation of
the desired compound that was used without further purification.
General Procedure for the Synthesis of Diaminopyridine
Derivatives (5n). A large excess of 1,5-diaminopyridine (0.03 mol,
10 equiv) was suspended in dry CH2Cl2 (60 mL) along with N,N′-
diisopropylethylamine (1.5 equiv, 4.5 mmol). A solution of 4n
(3 mmol, 1 equiv) in CH2Cl2 (20 mL) was then added dropwise
with stirring at 25 °C. The mixture was then brought to reflux,
which was maintained for 5 days. The mixture was allowed to cool
and then filtered. The filtrate was washed with water (3 × 100
mL), and the organic phase was collected and dried over MgSO4,
and the solvent was removed under reduced pressure. The crude
product was then purified by column chromatography on silica
(eluent: CH2Cl2/ethyl acetate 80:20).
General Procedure for the Synthesis of Acyclic Receptors
Tn, n ) 1, 3, 4, 5, 6. 5-t-Butylisophthalic acid (68 mg, 304 µmol)
was suspended in dry CH2Cl2 (30 mL) to which one drop of
anhydrous DMF was added. A solution of oxalyl chloride (1 mL,
11.5 mmol) in dry CH2Cl2 (20 mL) was then added dropwise, and
the resulting mixture was heated under reflux for 14 h. The solution
thus obtained was cooled, and the volatile components were
removed under reduced pressure to afford a brown oil that was
dried at 60 °C under vacuum for 5 h, dissolved in dry THF (20
mL), and added dropwise to a solution of 5n (670 µmol) and
triethylamine (720 µmol) in dry THF (40 mL) with stirring. After
14 h of stirring at 25 °C, the mixture was filtered, and the solvent
was removed under vacuum. The solid thus obtained was purified
by column chromatography on alumina (CH2Cl2/methanol, gradient
0-2%).
UV-Vis Method. A similar protocol to that used for the
fluorescence titrations was followed, monitoring the modifications
of absorbance between 280 and 330 nm. In both cases, the binding
constants were calculated using the Letagrop-spefo program.17
1H NMR Method. The receptor (solution concentration between
5 × 10-4 and 6 × 10-3 M) in 0.4 mL of CDCl3 was titrated with
a stock solution of guest (typical concentration between 1 × 10-2
and 6 × 10-2 M) in the same receptor solution. The downfield
shifts of the receptor amide NH was monitored as a function of
guest concentration. Addition was continued through 9-20 equiv.
The resultant titration curve was analyzed by using a nonlinear
regression method with the WinEqNMR18 computer program.
General Procedure for the Synthesis of Ethyl-9-anthryloxy-
alkyloate (2n). Anthrone (3.0 g, 15 mmol), K2CO3 (2.35 g, 17
mmol), and acetone (dried over molecular sieves, 150 mL) were
placed in a 250 mL round-bottomed flask equipped with a reflux
condenser. After the addition of ethyl-n-bromoenoate (0.023 mol,
1.5 equiv), the mixture was heated under reflux for 24 h. The
mixture was then allowed to cool to room temperature and filtered,
and the solvent was removed under reduced pressure. The residue
was then dissolved in 50 mL of CH2Cl2, washed with H2O (3 ×
20 mL), and dried over MgSO4. After removal of the solvent, the
crude product was purified by column chromatography (see
Supporting Information for exact conditions).
General Procedure for the Synthesis of Carboxylic Deriva-
tives (3n). Compound 2n (10 mmol) was dissolved in 80 mL of
ethanol in a round-bottomed flask equipped with a reflux condenser.
After the addition of an aqueous solution of NaOH (25 mmol in
10 mL), the mixture was heated under reflux for 14 h and then
allowed to cool to room temperature. The solvent was then removed
under vacuum, giving a solid that was then dissolved in 250 mL
of distilled water. Addition of 1 mL of concentrated hydrochloric
acid under stirring led to the precipitation of the compounds that
were collected by filtration and dried under vacuum at 60 °C for
14 h.
General Procedure for the Synthesis of Macrocyclic Com-
pounds TnC, n ) 3, 4, 5, 6. A solution of Tn in 50 mL of distilled
CH2Cl2 at c ) 5 10-4 M was degassed and irradiated under stirring
for 14 h with a Hg Lamp. After removal of the solvent, the solid
was dissolved in THF, precipitated with hexane, and dried at 25
°C under vacuum.
Acknowledgment. Financial support from the CNRS, the
French ministry of Education and Research, the Re´gion Aquita-
ine, and the EPSRC (award of PDRA Grant GR/S07438/02 to
Y.M.) is gratefully acknowledged. We thank the EPSRC national
mass spectrometry service (Swansea) for carrying out measure-
ments.
Supporting Information Available: General experimental
details, spectral characterization (1H NMR, 13C NMR, HRMS) for
all compounds, and elemental analysis of 2n, 3n, and Tn. Job plot
(T5 with 6) and NMR titration of T3, T3C, T6, and T6C with 6
and T6 with 7. This material is available free of charge via the
Internet at http://pubs.acs.org.
General Procedure for the Synthesis of Activated Ester
Derivatives (4n). Compound 3n (4 mmol) and N-hydroxysuccin-
imide (1.1 equiv) were dissolved in dry ethyl acetate (40 mL). A
solution containing N,N′-dicyclohexylcarbodiimide (1.1 equiv) in
ethyl acetate (20 mL) was then added under stirring, which was
maintained for 48 h. The mixture was then filtered, and the filtrate
JO061528A
J. Org. Chem, Vol. 71, No. 22, 2006 8531