Synthesis, optical properties, and LFER analysis of solvent-dependent binding constants of Hamilton-receptor-connected merocyanine chromophores

Article abstract of DOI:10.1021/jo801083b

(Chemical Equation Presented) A merocyanine dye equipped with a Hamilton-receptor unit has been synthesized that enables strong noncovalent binding of other merocyanine dyes bearing barbituric acid acceptor groups by six hydrogen bonds. NMR and UV/vis titration experiments in toluene, chloroform, dichloromethane, dioxane, and THF provide evidence for the formation of 1:1 complexes even in the dipolar solvents. An enhanced binding strength is observed for the more dipolar merocyanine dyes in the head-to-tail assembly structure with binding constants up to > 10⁸ M^-1 in toluene. In the present bimolecular complexes two merocyanine chromophores are assembled in a head-to-tail fashion that affords increased dipole moments as demanded for efficient electric field induced poling processes in nonlinear optical and photorefractive polymeric hosts. The solvent dependency of the binding constants for various barbituric acid dye-Hamilton receptor complexes as well as a perylene imide-melamine complex reveals linear free energy relationships (LFER) that allow for an estimation of binding constants larger than 10¹² M^-1 for Hamilton receptor organized head-to-tail merocyanine bimolecular complexes in aliphatic solvents. It is suggested that such LFER are valuable tools for the estimation of binding constants in solvents where experimental binding constants cannot be determined because of solubility or spectroscopic problems.

Full text of DOI:10.1021/jo801083b

Synthesis, Optical Properties, and LFER Analysis of
Solvent-Dependent Binding Constants of
Hamilton-Receptor-Connected Merocyanine Chromophores
Johann Schmidt, Ralf Schmidt, and Frank Wu¨rthner*
UniVersita¨t Wu¨rzburg, Institut fu¨r Organische Chemie, Am Hubland, 97074 Wu¨rzburg, Germany
wuerthner@chemie.uni-wuerzburg.de
ReceiVed May 19, 2008
A merocyanine dye equipped with a Hamilton-receptor unit has been synthesized that enables strong
noncovalent binding of other merocyanine dyes bearing barbituric acid acceptor groups by six hydrogen
bonds. NMR and UV/vis titration experiments in toluene, chloroform, dichloromethane, dioxane, and
THF provide evidence for the formation of 1:1 complexes even in the dipolar solvents. An enhanced
binding strength is observed for the more dipolar merocyanine dyes in the head-to-tail assembly structure
with binding constants up to >108 M-1 in toluene. In the present bimolecular complexes two merocyanine
chromophores are assembled in a head-to-tail fashion that affords increased dipole moments as demanded
for efficient electric field induced poling processes in nonlinear optical and photorefractive polymeric
hosts. The solvent dependency of the binding constants for various barbituric acid dye-Hamilton receptor
complexes as well as a perylene imide-melamine complex reveals linear free energy relationships (LFER)
that allow for an estimation of binding constants larger than 1012 M-1 for Hamilton receptor organized
head-to-tail merocyanine bimolecular complexes in aliphatic solvents. It is suggested that such LFER
are valuable tools for the estimation of binding constants in solvents where experimental binding constants
cannot be determined because of solubility or spectroscopic problems.
Introduction
introduced by Chang and Hamilton in 1988,4 which contains
two properly preorganized diacylaminopyridine units for the
efficient complexation of barbituric acids by six hydrogen bonds
with binding constants of 2 × 104 M-1 in chloroform at room
temperature. More recently, this receptor unit has been applied
as a noncovalent contact between electron-donor and electron-
The strength and directionality of hydrogen bonding is of
paramount importance for the folding and assembly of natural
macromolecules. Hydrogen bonding has also been amply applied
in numerous supramolecular systems to achieve desirable
structures with outstanding properties including molecular
recognition,1 supramolecular polymerization,2 and self-replica-
tion.3 One of the most useful synthetic receptor units was
(2) (a) Brunsveld, L.; Folmer, B. J. B.; Meijer, E. W.; Sijbesma, R. P. Chem.
ReV. 2001, 101, 4071–4097. (b) Schmuck, C.; Wienand, W. Angew. Chem., Int.
Ed. 2001, 40, 4363–4369. (c) Binder, W. H.; Zirbs, R. AdV. Polym. Sci. 2007,
207, 1–78.
* To whom correspondence should be addressed. Tel: + 49 (0)931-8885340.
Fax: + 49-(0)931-8884756.
(1) (a) Rebek, J. Angew. Chem., Int. Ed. Engl. 1990, 29, 245–255. (b)
Zimmermann, S. C.; Corbin, F. S. Struct. Bonding (Berlin) 2000, 96, 63–94. (c)
Prins, L. J.; Reinhoudt, D. N.; Timmermann, P. Angew. Chem., Int. Ed. 2001,
40, 2382–2426. (d) Sessler, J. L.; Lawrence, C. M.; Jayawickramarajah, J. Chem.
Soc. ReV. 2007, 36, 314–325.
(3) (a) Von Kiedrowski, G. Bioorg. Chem. Front. 1993, 3, 113–146. (b)
Tjivikua, T.; Ballester, P.; Rebek, J. J. Am. Chem. Soc. 1990, 112, 1249–1250.
(c) Lee, D. H.; Granja, J. R.; Martinez, J. A.; Severin, K.; Ghadiri, M. R. Nature
1996, 382, 525–528. (d) Kassianidis, E.; Philp, D. Angew. Chem., Int. Ed. 2006,
45, 6344–6348.
(4) Chang, S.-K.; Hamilton, A. D. J. Am. Chem. Soc. 1988, 110, 1318–1319.
10.1021/jo801083b CCC: $40.75
Published on Web 07/22/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 6355–6362 6355

Schmidt et al.
SCHEME 1. Concept for the Hydrogen Bond Directed
Formation of Head-to-Tail Bismerocyanine Complexes with
Enhanced Dipole Momentsa
SCHEME 2. Synthesis of Hamilton-Receptor-Functionalized
Merocyanine 9
a The red arrows represent the orientation of ground state dipole moments
of the merocyanine dyes.
acceptor dyes for photoinduced electron-transfer studies,5 for
the design of gelators for organic solvents,6 for the formation
of supramolecular polymers,7 for the synthesis of supramolecular
dendrimers,8 and for the binding of barbituric acids to surfaces.9
Furthermore, related systems based on melamines afforded [2
× 2] grids10 as well as liquid crystals, rosette-type cyclic
assemblies, and fluorescent gels bearing merocyanine dyes.11,12
We became interested in this versatile receptor unit due to its
intriguing orientation of two dipolar merocyanines in a bimo-
lecular complex as depicted in Scheme 1. In such a supramo-
lecular arrangement strong 6-fold hydrogen bonding is expected
to overcome the otherwise preferred formation of antiparallel
dimer aggregates of merocyanine dyes13 that can hardly be
oriented by electric fields owing to vanished dipole moments.14
In contrast, a bimolecular complex as shown in Scheme 1
provides an increased dipole moment as demonstrated by
electrooptical absorption spectroscopy in a recent communica-
tion.15 Such orientation of merocyanine dyes by external electric
fields is a highly desirable property for nonlinear optical and
photorefractive polymeric composite materials.16,17 In this paper,
we describe the synthesis of this Hamilton-receptor-function-
alized merocyanine dye and investigate its complexation proper-
ties in detail. In particular, we show that linear free energy
relationships (LFER) are given for the solvent-dependent binding
constants of these hydrogen-bonded complexes from which
valuable information can be deduced.
Results and Discussion
Synthesis. The Hamilton-receptor-functionalized merocya-
nine dye 9 was synthesized according to the synthetic route
outlined in Scheme 2. The key step of this sequence was the
synthesis of pyridine hydrochloride 3. This compound was
obtained by the reaction of 5-aminoisophthalic acid 1 with
dehydroacetic acid 2 in aqueous hydrochloric acid according
to Hu¨nig and Ko¨brich.18 It is noteworthy that the initially
attempted condensation with 2,6-dimethyl-4-pyrone failed
owing to the insufficient nucleophilicity of the aromatic
amine. Subsequently, compound 3 was transformed into its
diethyl ester derivative 4 by conventional esterification.
Amidation of diester 4 with monolithiated 2,6-diaminopyri-
dine afforded diamide 6, which was acylated with butanoyl
chloride or 3,3-dimethylbutanoyl chloride to give the Hamil-
ton-receptor-functionalized pyridone 7 as precursor for the
target compound 9. The Knoevenagel condensation reaction
of the CH-acidic barbiturate 8 with pyridone 7 afforded the
desired receptor-functionalized merocyanine dye 9.
(5) (a) Dirksen, A.; Hahn, U.; Schwanke, F.; Nieger, M.; Reek, J. N. H.;
Vo¨gtle, F.; De Cola, L. Chem. Eur. J. 2004, 10, 2036–2047. (b) McClenaghan,
N. D.; Grote, Z.; Darriet, K.; Zimine, M.; Williams, R. M.; De Cola, L.; Bassani,
D. M. Org. Lett. 2005, 7, 807–810. (c) Molard, Y.; Bassani, D. M.; Desvergne,
J.-P.; Horton, P. N.; Hursthouse, M. B.; Tucker, J. H. R. Angew. Chem., Int. Ed.
2005, 44, 1072–1075. (d) Wessendorf, F.; Gnichwitz, J.-F.; Sarova, G. H.; Hager,
K.; Hartnagel, U.; Guldi, D. M.; Hirsch, A. J. Am. Chem. Soc. 2007, 129, 16057–
16071.
(6) Inoue, K.; Ono, Y.; Kanekiyo, Y.; Ishi-i, T.; Yoshihara, K.; Shinkai, S.
J. Org. Chem. 1999, 64, 2933–2937.
(7) Berl, V.; Schmutz, M.; Krische, M.; Khoury, R.; Lehn, J.-M. Chem. Eur.
J. 2002, 8, 1227–1244.
(8) (a) Maurer, K.; Hager, K.; Hirsch, A. Eur. J. Org. Chem. 2006, 3338–
3347. (b) Hager, K.; Hartnagel, U.; Hirsch, A. Eur. J. Org. Chem. 2007, 1942–
1956.
(9) Motesharei, K.; Myles, D. C. J. Am. Chem. Soc. 1994, 116, 7413–7414.
(10) Lipkowski, P.; Bielejewska, A.; Kooijman, H.; Spek, A. L.; Timmer-
mann, P.; Reinhoudt, D. N. Chem. Commun. 1999, 1311–1312.
(11) (a) Wu¨rthner, F.; Yao, S.; Heise, B.; Tschierske, C. Chem. Commun.
2001, 2260–2261. (b) Prins, L. J.; Thalacker, C.; Wu¨rthner, F.; Timmermann,
P.; Reinhoudt, D. N. Proc. Nat. Acad. Sci. U.S.A. 2001, 98, 10042–10045.
(12) (a) Yagai, S.; Higashi, M.; Karatsu, T.; Kitamura, A. Chem. Mater. 2004,
16, 3582–3585. (b) Yagai, S.; Higashi, M.; Karatsu, T.; Kitamura, A. Chem.
Commun. 2006, 1500–1502. (c) Yagai, S.; Ishii, M.; Karatsu, T.; Kitamura, A.
Angew. Chem., Int. Ed. 2007, 46, 8005–8009.
The reference receptor 13, which lacks a merocyanine moiety,
was synthesized by acylation of compound 12 with 3,3-
(15) Wu¨rthner, F.; Schmidt, J.; Stolte, M.; Wortmann, R. Angew. Chem.,
Int. Ed. 2006, 45, 3842–3846.
(16) (a) Verbiest, T.; Houbrechts, S.; Kauranen, M.; Clays, K.; Persoons, A.
J. Mater. Chem. 1997, 7, 2175–2189. (b) Wu¨rthner, F.; Wortmann, R.; Meerholz,
K. Chem. Phys. Chem. 2002, 3, 17–31.
(13) (a) Dalton, L. R.; Harper, A. W.; Robinson, B. H. Proc. Nat. Acad. Sci.
USA 1997, 94, 4842–4847. (b) Wu¨rthner, F.; Yao, S. Angew. Chem., Int. Ed.
2000, 39, 1978–1981. (c) Wu¨rthner, F.; Yao, S.; Debaerdemaeker, T.; Wortmann,
R. J. Am. Chem. Soc. 2002, 124, 9431–9447.
(17) (a) Zhu, P.; Kang, H.; Facchetti, A.; Evmenenko, G.; Dutta, P.; Marks,
T. J. J. Am. Chem. Soc. 2003, 125, 11496–11497. (b) Saadeh, H.; Wang, L.;
Yu, L. J. Am. Chem. Soc. 2000, 122, 546–547.
(14) Wortmann, R.; Ro¨sch, U.; Redi-Abshiro, M.; Wu¨rthner, F. Angew.
Chem., Int. Ed. 2003, 42, 2080–2083.
(18) Hu¨nig, S.; Ko¨brich, G. Liebigs Ann. Chem. 1958, 617, 181–202.
6356 J. Org. Chem. Vol. 73, No. 16, 2008

Merocyanine Chromophores
SCHEME 3. Synthesis of the Reference Hamilton Receptor
13
FIGURE 1. UV/vis absorption spectra of the barbituric acid mero-
cyanine dyes 14b (dashed line), 14a (dash-dotted line), and 14c (solid
line) in 1,4-dioxane at 298 K.
SCHEME 4. Complex Formation between the Hamilton
Receptors 9 and 13 and Barbituric Acid Merocyanines
14a-ca
TABLE 1. Dipole Moments and UV/vis Absorption Data of
Merocyanine Dyes 14a-c
dye µ (D)a ∆µ (D)a
solvent (ꢀr)
λmax (nm) ꢀ (M-1 cm-1
)
14a
6.2
+2.4
-3.9
1,4-dioxane (2.21)
THF (7.39)
462
462
469
467
380
379
377
372
371
510
506
500
487
483
92 700
80 600
81 800
81 700
50 600
50 600
49 900
45 900
46 400
110 800
109 700
103 200
89 000
87 400
CHCl3 (4.81)
CH2Cl2 (8.93)
toluene (2.38)
1,4-dioxane (2.21)
THF (7.39)
CHCl3 (4.81)
CH2Cl2 (8.93)
toluene (2.38)
1,4-dioxane (2.21)
THF (7.39)
14b 10.1
14c
13.5
-4.2
CHCl3 (4.81)
CH2Cl2 (8.93)
a Determined by electrooptical absorption spectroscopy (EOAM) at
room temperature in 1,4-dioxane. [See the Experimental Section and ref
20.] “Gas phase” dipole moments have been calculated by a solvent
correction within the approximation of Onsager’s continuums model.
the solute by the solvent environment.21 The solvatochromism
of dye 14a with its almost cyanine-like electronic structure (i.e.,
∆µ close to zero) is rather small, whereas for the more dipolar
dyes 14b and 14c with ∆µ < 0 a negative solvatochromism is
noted. For merocyanine 14c, the most pronounced color shift
from orange (in the little polar solvent toluene) to yellow (in
the polar solvent dichloromethane) is observed. For all dyes,
we observe a significant decrease of the absorption coefficient
ꢀ (Table 1) upon increasing the solvent polarity and a concomi-
tant broadening of the absorption band. This indicates a change
of the dyes’ electronic structure from a more cyanine-like to a
betaine-like chromophore evoked by the polarizing effect of the
dipolar and polarizing solvent environment.22
Solvent-Dependent Complexation Properties. A significant
color change is observed for merocyanine dyes 14a-c not only
upon changing the solvent but also upon complexation with a
Hamilton receptor (Figure 2). In the least polar solvent toluene
a shift of the absorption maximum from 510 to 498 nm is
observed for dye 14c during the titration with receptor 13. Thus,
the partial exchange of the toluene solvation shell by a 6-fold
hydrogen-bonding Hamilton receptor affords the same blue-
a X denotes the electron-donor unit.
dimethylbutanoyl chloride, while 12 was prepared according
to literature procedures (Scheme 3).4 Merocyanine dyes with
barbituric acid acceptor groups 14a-c (Scheme 4) applied in
this work for the complexation with receptor 9 were prepared
by known literature methods.19 The synthetic details and
characterization data for all unknown compounds are given in
the Experimental Section.
Solvent-Dependent Properties of Merocyanines 14a-c.
Three merocyanine dyes 14a-c (see Scheme 4) bearing
barbituric acid acceptor groups were chosen for the investigation
of the hydrogen-bonding strength of the Hamilton receptor
equipped with a merocyanine dye in the solvents toluene,
chloroform, dichloromethane, dioxane, and THF. The three
merocyanines are distinguished, on the one hand, by their color
and position of their absorption maxima, i.e., at about 380 (pale
yellow, 14b), 460 (yellow, 14a), and 510 nm (orange, 14c) in
1,4-dioxane (Figure 1) and, on the other hand, by the magnitude
of their dipole moments µg and their dipole moment changes
∆µ upon optical excitation (Table 1).20 As expected for such
strongly dipolar dyes, the wavelengths of the absorption maxima
vary in solvents of different polarity (Table 1). This solvato-
chromism can be related primarily to the magnitude of the dipole
moment change ∆µ upon optical excitation, i.e., a different
energetic stabilization of the ground and the excited states of
(21) Reichardt, C. SolVents and SolVent Effects in Organic Chemistry, 3rd
ed.; Wiley-VCH: Weinheim, Germany, 2002.
(22) (a) Brooker, L. G. S.; Keyes, G. A. J. Am. Chem. Soc. 1951, 73, 5356–
5358. (b) Hu¨nig, S.; Rosenthal, O. Liebigs Ann. Chem. 1954, 592, 162–179. (c)
Radeglia, R.; Da¨hne, S. J. Mol. Struct. 1970, 5, 399–411. (d) Bourhill, G.; Bre´das,
J. L.; Cheng, L.-T.; Marder, S. R.; Meyers, F.; Perry, J. W.; Tiemann, B. J. Am.
Chem. Soc. 1994, 116, 2619–2620. (e) Archetti, G.; Abbotto, A.; Wortmann, R.
Chem. Eur. J. 2006, 12, 7151–7160. (f) Wu¨rthner, F.; Archetti, G.; Schmidt, R.;
Kuball, H.-G. Angew. Chem., Int. Ed. 2008, 47, 4529–4532.
(19) Wu¨rthner, F. Synthesis 1999, 12, 2103–2113.
(20) Stolte, M.; Kuball, H.-G. Personal communication.
J. Org. Chem. Vol. 73, No. 16, 2008 6357

Schmidt et al.
TABLE 2. Binding Constants Kass (M-1) for the Complexes
1
13:14a-c and 9:14a-c from H NMR Titration Experiments in
Dioxane-d8 and THF-d8 at 298 Ka
13:14
9:14
dioxane-d8
THF-d8
dioxane-d8
THF-d8
14a
14b
14c
310
n.d.
1800
1500
b
b
b
5000b
2.2 × 104
1.8 × 104
3.6 × 104
3.1 × 104
1.5 × 105
8.2 × 104
1.3 × 105
a From constant host titration experiments in which the Hamilton
receptors were the host molecules. The binding constants are the
average value from the two amide NH group data sets that were
independently analyzed by nonlinear regression analysis. The
experimental errors are ca. (20% for K values <5000 but increase
significantly for higher K values where only the order of magnitude can
be correctly assigned. b From a constant host titration in which 14b was
the host and the shift of the imide and/or 3,5 protons of the
dihydropyridine units were analyzed by the nonlinear regression method.
FIGURE 2. Left: Solutions of merocyanine dye 14c (orange) and a
1:1 mixture of merocyanine dye 14c and Hamilton receptor 13 (yellow)
in 1,4-dioxane at identical concentrations. Right: UV/vis titration of
merocyanine dye 14c at a constant concentration of 1 × 10-5 M with
increasing amounts of Hamilton receptor 13 in toluene at 298 K. The
inset shows the titration isotherm at a wavelength of 470 nm.
dyes, (2) the impact of a dipolar merocyanine substituent at
the Hamilton receptor, and (3) the impact of the solvent. For
the latter two aspects, the effects are rather small and hardly
above the error range of the experiment. In general, the values
in dioxane are a bit smaller than those in THF. On the basis
of the significantly higher permittivity value of THF (ꢀr )
7.39) compared to dioxane (ꢀr ) 2.21) a much larger effect,
i.e., much higher binding constants, in dioxane was expected.
Obviously, it is not the dipolarity but the hydrogen-bond
acceptor capability of the solvent that counts. Here both solvents
are of similar nature and dioxane has even two ether oxygen
atoms as hydrogen bond acceptors and THF has only one which
may compensate for the smaller dipolarity of this solvent. It is
tempting to consider a specific hydrogen-bonding mode for
dioxane in which one solvent molecule is chelated between two
amide hydrogen bond donating units of the two diacylaminopy-
ridine arms of the Hamilton receptor. But this idea is discarded
based on our data analysis by linear free energy relationships
(vide infra).
Likewise, only a small difference is found in the comparison
of the binding strengths of the two Hamilton receptors 9 and
13. With one exception (13:14c in THF; but here the values
are prone to significant experimental errors due to their large
magnitude leading to very steep binding isotherms in NMR
titrations in the millimolar concentration regime), it is always
the merocyanine-functionalized Hamilton receptor 9 that exhibits
the larger binding strength. Two possible reasons might account
for this effect. One is a conformational effect, i.e., the bulky
merocyanine substituent at the phenyl group might contribute
to a better preorganization of the two arms of the Hamilton
receptor (for a discussion of the different conformations of this
receptor, see ref 7). The other possibility is an attractive
dipole-dipole interaction between the bound barbituric acid dye
and the Hamilton-receptor-appended merocyanine dye. Obvi-
ously, these effects are, however, not very significant.
FIGURE 3. 1H NMR titration experiments for the host-guest system
9:14b. Part a shows the change of the chemical shifts for the
dihydropyridine protons 3,5 (red) in CDCl3 (circles) and dioxane-d8
(squares) and part b shows the change of the imide protons (blue) in
THF-d8 (triangles) and dioxane-d8 (squares) upon addition of increasing
amounts of Hamilton-receptor-functionalized merocyanine 9 at 298 K
and binding isotherms calculated by nonlinear regression analysis.
shifted absorption band as found for dye 14c if completely
solvated by the polar solvent THF (Table 1). Accordingly, the
concomitant shift of the absorption bands upon complexation
offers a convenient tool for the determination of the binding
constant by UV/vis titration experiments (Scheme 4). In
addition, 1H NMR titration is applicable to follow the 1:1
complex formation. Here, the most significant shift was found
consistently for the imide protons of the barbituric acid subunit
(see Figure S1 in the Supporting Information). However, owing
to strong broadening of these proton signals in some solvents
(particularly in CDCl3) during the titration, other protons
afforded often higher quality binding isotherms despite a less
pronounced change of the chemical shift (Figure 3). A reversal
of host and guest molecules is possible as well due to notable
signal shifts of the amide protons of the Hamilton receptor in
1H NMR titration experiments (Figure S2 in the Supporting
Information).
In Table 2 the binding constants for the 1:1 complexes
between the Hamilton receptors 9 (with appended merocya-
nine) and 13 (reference without additional substituent) and
the barbituric acid dyes 14a-c in dioxane and in THF are
collected. This data set allows us to analyze the substituent
effects on the binding strength in three directions: (1) the
impact of the electron-donor subunit of the three merocyanine
On the other hand, a very significant effect is observed for
the series of three different barbituric acid dyes 14a-c. For
both Hamilton receptors 9 and 13, a strong increase of the
binding constants by about 2 orders of magnitude is observed
in the series 14a f 14b f 14c. In the same direction an
increased dipolarity of the dyes is given (Table 1) as well as an
increased contribution of the zwitterionic resonance structures.
Scheme 5 shows the two most extreme resonance structures,
i.e., a nonpolar polyene-type structure (the left one) and a
strongly dipolar zwitterionic structure with two aromatic
heterocycles (the right one). The amazingly high acidity of
6358 J. Org. Chem. Vol. 73, No. 16, 2008

Merocyanine Chromophores
TABLE 3. Binding Constants Kass (M-1) for the Complexes
13:14a,b and 9:14a Determined by UV/Vis Titration Experiments in
Chloroform, Dichloromethane, and Toluene at 298 K and Estimated
by Linear Free Energy Relationships (LFER) for Methylcyclohexane
(MCH) and n-Hexanea
SCHEME 5. Two Resonance Structures for Merocyanine
14c
CHCl3
CH2Cl2
toluene
MCH
n-hexane
13:14a 8.4 × 105 1.5 × 106 3.8 × 108 1.1 × 1012 4.0 × 1012
13:14b 1.3 × 106 6.2 × 106 4.7 × 108 1.2 × 1013 4.9 × 1013
c
barbituric acids is explained by a considerable contribution of
polar bonds as shown in the right structure, and the large dipole
moment of dye 14c provides further evidence for the important
zwitterionic contribution to the electronic structure of these dyes.
Thus, the observed increase in the binding strength in the series
14a f 14b f 14c can be related to an increasing contribution
of zwitterionic resonance structures in the given series. As more
charge density is accumulated at the barbituric acid acceptor
unit (i.e., at the carbonyl oxygen atoms) the higher is the
complexation constant for hydrogen bond directed bimolecular
association with the Hamilton receptors 9 and 13.
To further elucidate the solvent effect on the binding constant
between barbituric acid dyes and Hamilton receptors, another
series of titration experiments was performed in the solvents
dichloromethane, chloroform, and toluene. For these solvents,
much higher binding constants are expected because they lack
the competing hydrogen bond acceptor capability of dioxane
and THF. For higher binding strength than given above (Table
2), lower concentrations of about 10-5 M are needed for an
accurate determination of the binding constants. Because of the
critical signal-to-noise ratio at such low concentrations in NMR
spectroscopy, these titration experiments were now carried out
by UV/vis spectroscopy. In the case of the reference Hamilton
receptor 13, these experiments were rather straightforward
because the absorption bands of this colorless receptor do not
interfere with those of guest merocyanines (see Figure 2).
Therefore, a comprehensive series of UV/vis titrations was
carried out for the two complexes 13:14a and 13:14b. For
complex 9:14a, the same experiments were carried out but data
analysis here was restricted to that part of the absorption band
of host 14a (λ > 480 nm) that is free from the absorbance of
guest 9 as confirmed by the saturation of the signal in the
binding isotherm (Figure 4, inset).
b
c
9:14a
5.2 × 106 5.8 × 106 >2 × 107 1.2 × 1013 4.9 × 1013
a The experimental errors are ca. (15% for K values <1 × 107 but
increase significantly for higher K values where only the order of
magnitude can be correctly assigned. b This experimental value could
only be estimated due to the problems arising from overlapping
absorption bands of guest and host molecules and the difficulties
encountered by working under very high dilution conditions. c In this
LFER analysis the estimated value in toluene was not included.
hydrogen bond donor solvent) and dichloromethane (dipolar
solvent), we note a more than 2 orders of magnitude higher
binding constant in the chlorinated solvents that lack the
hydrogen bond acceptor capabilities of the ether solvents. A
further increase by about 2 orders of magnitude is observed in
toluene that lacks hydrogen-bond donor/acceptor capabilities and
dipolarity as well. Thus, specific hydrogen bond based solvation
as well as unspecific solvation effects contribute to the measured
binding constants. These results are in accordance with the well-
known fact that the specific solvation by hydrogen-bond donor
and hydrogen-bond acceptor solvents cannot be properly
described by macroscopic permittivity functions and has led to
the development of empirical multiparameter analyses that
include hydrogen-bond donor and hydrogen-bond acceptor
strength parameters of the respective solvents.23 In the field of
medicinal chemistry Abraham and co-workers have widely
applied such parameters to quantify the binding strength of drugs
to biological receptors in QSAR (quantitative structure-activity
relationship, Abraham model).24
With our available data set it is interesting to analyze the
solvent-dependent binding constants for the three available
complexes by means of a linear free energy relationship (LFER).
As shown in Figure 5a, the solvent-dependent Gibbs free
complexation energies ∆G0 ) -RT ln(Kass/M-1) reveal a quite
good LFER ∆G0(13:14b) ) 1.06 ×∆G0(13:14a) with a cor-
relation coefficient of 0.891. The slope of almost unity is in
accordance with the nearly identical binding units based on
6-fold hydrogen bonding between two different barbituric acids
with the same Hamilton receptor. On the logarithmic energy
scale only a small impact of the respective barbituric acid units
is found leading to slightly higher ∆G0 values for 13:14b than
for 13:14a, i.e., a slope of slightly larger than unity. Likewise
∆G0(9:14a) ) 1.13 × ∆G0(13:14a) is obtained if the Hamilton
receptor unit is exchanged.
The combined data sets in Tables 2 and 3 allow now for a
more meaningful comparison of the solvent effects on the
binding strength between the Hamilton receptors and the
barbituric acid dyes. Thus, while the values in THF and dioxane
(dipolar and hydrogen bond acceptor solvents) are pretty similar
as well as those in chloroform (weakly dipolar and weak
Even more interesting, a pretty good LFER is also found with
the Gibbs free binding energies for the triple hydrogen bond based
bimolecular complex between perylene imide 15 and melamine
16 (Scheme 6) that was investigated by our group a couple of years
ago25 (Figure 5b):
∆G0(13:14a) ) 2.54 × ∆G0(15:16) r2 ) 0.953
∆G0(13:14b) ) 2.76 × ∆G0(15:16) r2 ) 0.893
FIGURE 4. UV/vis titration of merocyanine dye 14a at a constant
concentration of 1 × 10-5 M with increasing amounts of receptor-
functionalized merocyanine 9 in CHCl3 at 298 K. The inset shows the
titration isotherm at a wavelength of 492 nm.
(23) (a) Taft, R. W.; Abboud, J.-L. M.; Kamlet, M. J.; Abraham, M. H. J.
Solution Chem. 1985, 14, 153–186. (b) Kamlet, M. J.; Abboud, J.-L. M.;
Abraham, M. H.; Taft, R. W. J. Org. Chem. 1983, 48, 2877–2887.
(24) Abraham, M. H. Chem. Soc. ReV. 1993, 22, 73–83.
J. Org. Chem. Vol. 73, No. 16, 2008 6359

Schmidt et al.
∆G0(9:14a) ) 2.76 × ∆G0(15:16) r2 ) 0.990
with a particular solvent as demonstrated above for 1,4-dioxane,
but they can also be applied for the estimation of binding
constants of systems where an accurate determination is
hampered by spectroscopic problems, as in our UV/vis studies
of 9:14a-c due to spectral overlap of host and guest absorption
bands or in some of our 1H NMR studies due to signal
broadening caused by dynamic exchange phenomena. Likewise,
they are applicable for those instances where trivial problems,
such as solubility limitations or just the existence of too large
or too small binding constants that require concentrations out
of the sensitivity range of the available spectroscopic technique,
prevent an accurate determination of the binding constant. To
give an example, the determination of binding constants for
complexes 13:14a-c and 9:14a-c in solvents of even lower
polarity than toluene is hard to achieve without having
performed more difficult competitive titration experiments where
one weakly bound guest molecule is replaced by a more strongly
binding one. However, with the values given in the literature25
for 15:16 in methylcyclohexane (21 000 M-1) and in n-hexane
(90 000 M-1) and the above LFER equations a proper estimation
is possible (Table 3). According to this analysis, we can safely
claim that complexes between barbituric acid dyes 14a-c and
Hamilton receptors 9 or 13 will even prevail in the low
nanomolar down to the picomolar concentration regime in
aliphatic solvents. Such high binding constants can be very
useful, e.g., they should enable the formation of electrooptically
active long-chain supramolecular polymer fibers26 even under
highly dilute conditions, which is one of the current goals of
our research.
The values for the slopes of 2.54-2.76 pinpoint the increased
binding strength of 6-fold versus 3-fold hydrogen bonding in
the respective bimolecular complexes while the high correlation
coefficient reveals an equal ratio of unspecific and specific
solvent effects on the binding enthalpies of these complexes.
In particular, this analysis does not reveal any special chelate-
type binding features between the solvent dioxane and the
Hamilton receptor as assumed at first glance based only on the
data sets for barbituric acid-Hamilton receptor complexes (see
above).
Such solvent-dependent LFER have been widely applied for
absorption energies and reaction rates,21,23 but rarely for binding
constants. This is rather surprising since LFER relationships
are quite a useful tool not only for revealing specific interactions
Conclusion
Our work has shown that 6-fold hydrogen bonding between
merocyanine dyes equipped with a Hamilton receptor and
merocyanine dyes bearing a barbituric acid acceptor moiety is
a powerful approach to direct the assembly of these dipolar dyes
into a desirable NLO-active head-to-tail orientation of two dyes
in a bimolecular complex. Pronounced spectral shifts and color
changes upon complexation reveal a polarization of the barbi-
turic acid merocyanine dye by 6-fold hydrogen bonding. On a
qualitative level, this effect was discussed as a kind of specific
solvation because similar spectral shifts could be observed upon
variation of the solvent polarity. In a future paper these effects
will be elucidated in a quantitative manner based on data from
electrooptical absorption spectroscopy.20 Additionally, we have
shown that linear free energy relationships (LFER) are given
for the solvent-dependent Gibbs binding enthalpies between
various series of hydrogen-bonded complexes. It is suggested
that such LFER are a valuable tool for the estimation of binding
constants in solvents where experimental binding constants
cannot be determined because of solubility or spectroscopic
problems.
FIGURE 5. Linear free energy relationships for the solvent-dependent
Gibbs free binding enthalpies for the bimolecular complexes: (a) 13:
14a and 13:14b and (b) 13:14b and 15:16. The data are shown in Tables
2 and 3 and in Table S2 in the Supporting Information.
SCHEME 6. Complex Formation between Perylene Imide
15 and Melamine 16 by Three Hydrogen Bonds
Experimental Section
1-(3,5-Dicarboxy)phenyl-2,6-dimethyl-4-pyridone Hydrochlo-
ride (3). To a suspension of 5-aminoisophthalic acid 1 (27.4 g,
(25) Wu¨rthner, F.; Thalacker, C.; Sautter, A.; Scha¨rtl, W.; Ibach, W.;
Hollricher, O. Chem. Eur. J. 2000, 6, 3871–3886. Notably, in this study no values
for toluene were given. However, due to the similarity of benzene and toluene
with regard to dipolarity and hydrogen-bonding properties it appeared reasonable
to combine values measured for 13:14a,b in toluene with values measured for
15:16 in benzene.
(26) Sijbesma, R. P.; Beijer, F. H.; Brunsveld, L.; Folmer, B. J. B.;
Hirschberg, J. H. K. K.; Lange, R. F. M.; Lowe, J. K. L.; Meijer, E. W. Science
1997, 278, 1601–1604.
6360 J. Org. Chem. Vol. 73, No. 16, 2008

Merocyanine Chromophores
3
151 mmol) and dehydroacetic acid 2 (27.4 g, 151 mmol) in H2O
(160 mL) was added an aqueous solution of HCl (37%, 97 mL)
and the resultant mixture was heated to 110 °C for 15 h. After
cooling to 0 °C, the precipitated gray solid was separated by
filtration and recrystallized from methanol to give pure 3 as a white
crystalline solid (30.5 g, 0.106 mol, 70%): mp 250 °C dec. 1H NMR
Hz, 2 H), 7.79-7.85 (m, 6H), 6.15 (s, 2H), 2.38 (t, J ) 7.4 Hz,
4H), 1.94 (s, 6H), 1.62 (m, 4H), 0.91 (t, 3J ) 7.4 Hz, 6H). HRMS
(ESI) m/z calcd for C33H36N7O5 [M + H]+ 610.2772, found
610.2775.
1-{3,5-Bis[(6-(3,3-dimethyl)butyrylamino)pyridine-2-yl]car-
bamoyl}phenyl-2,6-dimethyl-4-pyridone (7a). Derivative 7a was
prepared according to the procedure described above for the pyridine
7 by using 3,3-dimethylbutanoyl chloride (1.32 g, 9.81 mmol)
instead of butanoyl chloride. The crude product was first purified
by silica gel column chromatography with EtOAc/EtOH 2:1 as
eluent and subsequently precipitated from highly saturated CH2Cl2
solution by adding n-hexane to give pure 7a (1.30 g, 1.95 mmol,
4
4
(400 MHz, MeOH-d4) δ 8.68 (t, J ) 1.5 Hz, 1H), 8.18 (d, J )
1.5 Hz, 2H), 7.04 (s, 2H), 2.10 (s, 6H). Anal. Calcd for C15H13NO5:
C, 55.65; H, 4.36; N, 4.33. Found: C, 55.56; H, 4.46; N, 4.31.
1-(3,5-Dicarbethoxy)phenyl-2,6-dimethyl-4-pyridone (4). To
a suspension of pyridone hydrochloride 3 (30.5 g, 0.106 mol) in
toluene (470 mL) were added ethanol (190 mL) and concentrated
H2SO4 (5.5 mL) and the mixture was heated to reflux at 110 °C by
using a water separator. After 1.5 h of heating hydrochloride 3 was
dissolved, and ethanol/toluene 1:2 (20 mL) was added to replace
the separated amount of toluene/H2O. While heating for a further
20 h, the reaction volume was kept constant by replacing the
separated amount of toluene/H2O with a ethanol/toluene 1:2 mixture.
After being cooled to room temperature, the solution was poured
into water (140 mL). The resultant solid was separated by filtration
and dissolved in chloroform (100 mL), then made basic (pH 9-10)
by adding saturated aqueous Na2CO3 solution. After separation of
the organic layer, the aqueous layer was extracted with chloroform
(3 × 40 mL). The combined organic layers were washed with water
(3 × 70 mL) and dried over Na2SO4, and the solvent was
evaporated. The residue was recrystallized from cyclohexane/ethyl
acetate to give pure 4 as a white crystalline solid (24.2 g, 70.5
mmol, 82%): mp 218-219 °C. 1H NMR (400 MHz, CDCl3) δ 8.83
(t, 4J ) 1.5 Hz, 1H), 8.08 (d, 4J ) 1.5 Hz, 2H), 6.38 (s, 2H), 4.47
1
46%): mp 287-290 °C. H NMR (400 MHz, DMSO-d6) δ 10.78
(br s, 2H), 9.97 (br s, 2H), 8.61 (t, 4J ) 1.5 Hz, 1H), 8.20 (d, 4J )
1.5 Hz, 2H), 7.79-7.85 (m, 6H), 6.15 (s, 2H), 2.30 (s, 4H), 1.94
(s, 6H) 1.02 (s, 18H). HRMS (ESI) m/z calcd for C37H44N7O5 [M
+ H]+ 666.3398, found 666.3393.
5-{1-[3,5-Bis[(6-butyrylamino)pyridine-2-yl]carbamoyl]phenyl-
2,6-dimethylpyridine-4-ylidene}-1,3-dibutylpyrdimidine-2,4,6-tri-
one (9). A mixture of pyridone 7 (300 mg, 0.492 mmol) in Ac2O
(10 mL) and AcOH (1 mL) was heated to 95 °C. At this temperature
a solution of N,N′-dibutylbarbituric acid (144 mg, 0.599 mmol) in
Ac2O (5 mL) and AcOH (1 mL) was added dropwise and the
resulting mixture was heated to 105 °C for 4 h. The solvent was
removed under reduced pressure and the residue was purified by
silica gel column chromatography with CH2Cl2/EtOH 40:1 f 10:1
as eluent. The product was then precipitated from highly saturated
CH2Cl2 solution by adding n-hexane to give 9 in a pure form as a
yellow solid (90 mg, 0.108 mmol, 22%): mp 321-322 °C. 1H NMR
3
3
4
(q, J ) 7.1 Hz, 4H), 1.92 (s, 6H), 1.45 (t, J ) 7.1 Hz, 6H). MS
(EI) m/z (%) 343 (57) [M]+, 315 (100) [M - CO]+. Anal. Calcd
for C19H21NO5: C, 66.46; H, 6.16; N, 4.08. Found: C, 66.27; H,
6.25; N, 4.05.
(400 MHz, MeOH-d4) δ 8.91 (s, 2H), 8.84 (t, J ) 1.6 Hz, 1H),
4
3
4
8.29 (d, J ) 1.6 Hz, 2H), 7.98 (dd, J ) 7.5 Hz, J ) 0.9 Hz,
2H), 7.81 (t, 3J ) 8.0 Hz, 2H), 7.74 (dd, 3J ) 7.5 Hz, 4J ) 0.9 Hz,
3
3
2H), 3.99 (t, J ) 7.5 Hz, 4H), 2.40 (t, J ) 7.5 Hz, 4H), 2.33 (s,
3
1-[3,5-Bis(6-aminopyridine-2-yl)carbamoyl]phenyl-2,6-dimethyl-
4-pyridone (6). 2,6-Diaminopyridine 5 (9.56 g, 87.6 mmol) was
dissolved in dry THF (150 mL) under an argon atomosphere and
the mixture was cooled to -78 °C. At this temperature tert-
buthyllithium (1.7 M in n-pentane, 51.5 mL, 87.6 mmol) was added
dropwise. Afterward a solution of pyridone 4 (6.00 g, 17.5 mmol)
in dry THF (200 mL) was added dropwise and the reaction mixture
was stirred for 4 h at -78 °C and an additional 16 h at room
temperature. The resulting suspension was poured into a saturated
aqueous solution of NaHCO3 (200 mL, pH 8-10). After extracting
the aqueous layer with CHCl3 (3 × 150 mL) the combined organic
layers were dried over MgSO4. The solvent was removed under
reduced pressure and the residue was recrystallized from methanol
to give pure 6 (5.80 g, 12.3 mmol, 71%): mp 317 °C dec. 1H NMR
6H), 1.74 (m, 4H), 1.63 (m, 4H), 1.38 (m, 4H), 1.01 (t, J ) 7.4
3
Hz, 6H), 0.98 (t, J ) 7.3 Hz, 6H). HRMS (ESI) m/z calcd for
C45H53N9NaO7 [M + Na]+ 854.3960, found 854.3963. Anal. Calcd
for C45H53N9O7 ·CH3OH: C, 63.95; H, 6.65; N, 14.59. Found: C,
63.75; H, 6.33; N, 14.63.
5-{1-[3,5-Bis[(6-(3,3-dimethyl)butyrylamino)pyridine-2-yl]car-
bamoyl]phenyl-2,6-dimethylpyridine-4-ylidene}-1,3-dibutylpyrdi-
midine-2,4,6-trione (9a). Compound 9a was prepared according to
the procedure described above for compound 9 by using pyridine
derivative 7a (500 mg, 0.751 mmol) instead of pyridine 7. The
crude product was first purified by silica gel column chromatog-
raphy with CH2Cl2/EtOH 40:1 f 10:1 as eluent and then
precipitated from highly saturated CH2Cl2 solution by adding
n-hexane to give 9a in a pure form as a yellow solid (130 mg,
0.146 mmol, 19%): mp 360-361 °C. 1H NMR (400 MHz, CDCl3/
4
(400 MHz, DMSO-d6) δ 10.55 (br s, 2H), 8.57 (t, J ) 1.6 Hz,
1H), 8.13 (d, 4J ) 1.6 Hz, 2H), 7.45 (t, 3J ) 7.8 Hz, 2H), 7.38 (dd,
3J ) 7.8 Hz, 4J ) 0.8 Hz, 2H), 6.28 (dd, 3J ) 7.8 Hz, 4J ) 0.8 Hz,
2H), 6.12 (s, 2H), 5.77 (s, 4H), 1.93 (s, 6H). MS (FAB,
3-nitrobenzyl alcohol) m/z 470 [M + H]+ (calcd 469.5). Anal. Calcd
for C25H23N7O3: C, 63.96; H, 4.94; N, 20.88. Found: C, 63.78; H,
5.11; N, 20.74.
4
MeOH-d4 1:1) δ 8.97 (s, 2H), 8.91 (t, J ) 1.5 Hz, 1H), 8.20 (d,
4J ) 1.5 Hz, 2H), 7.98 (d, 3J ) 8.1 Hz, 2H), 7.79 (t, 3J ) 8.1 Hz,
2H), 7.69 (d, 3J ) 8.1 Hz, 2H), 3.98 (t, 3J ) 7.6 Hz, 4H), 2.32 (s,
6H), 2.29 (s, 4H), 1.66 (m, 4H), 1.42 (m, 4H), 1.12 (m, 18H), 0.98
(t, 3J ) 7.3 Hz, 6H). MS (FAB, 3-nitrobenzylalcohol) m/z 888 [M]+
(calcd 888.08). Anal. Calcd for C49H61N9O7: C, 66.27; H, 6.92; N,
14.19. Found: C, 65.80; H, 6.99; N, 13.82.
1-{3,5-Bis[(6-butyrylamino)pyridine-2-yl]carbamoyl}phenyl-
2,6-dimethyl-4-pyridone (7). To a suspension of pyridone 6 (2.26
g, 4.81 mmol) in dry THF (140 mL) under an argon atmosphere
was added NEt3 (1.5 mL, 1.12 g, 11.1 mmol) and afterward a
solution of butanoyl chloride (1.16 mL, 1.18 g, 11.1 mmol) in dry
THF (40 mL) was added dropwise at 0 °C. The mixture was stirred
for 3 h at 0 °C and for an additional 20 h at room temperature. The
resulting suspension was poured into a saturated aqueous solution
of NaHCO3 (200 mL, pH 8-10). The aqueous layer was extracted
with CHCl3 (4 × 50 mL) and the combined organic layers were
dried over MgSO4. The solvent was removed under reduced
pressure and the obtained solid crude product was recrystallized
from EtOAc/MeOH 1:4 to give pure 7 (2.10 g, 3.44 mmol, 72%):
1,3-Bis{[(6-(3,3-dimethyl)butyrylamino)pyridine-2-yl]carba-
moyl}benzene (13). To a solution of diamine 12 (1.50 g, 4.31
mmol) and NEt3 (1.57 mL, 1.13 g, 11.2 mmol) in dry THF (100
mL) was added 3,3-dimethylbutanoyl chloride (1.39 mL, 1.33 g,
9.88 mmol) in dry THF (50 mL) dropwise at 0 °C. The reaction
mixture was stirred for 1 h at 0 °C and then an additional 14 h at
room temperature. Afterward, the mixture was poured into a
saturated aqueous solution of NaHCO3 (200 mL) and extracted with
CHCl3 (3 × 150 mL), and the united organic phases were dried
over MgSO4. The solvent was removed under reduced pressure and
the crude product was purified by precipitation from CH2Cl2/n-
hexane to give pure 13 as a white solid (880 mg, 1.62 mmol, 38%):
mp 133-135 °C. 1H NMR (400 MHz, CDCl3) δ 8.46 (t, 4J ) 1.7
1
mp 293-295 °C. H NMR (400 MHz, DMSO-d6) δ 10.76 (br s,
2H), 10.04 (br s, 2H), 8.60 (t, 4J ) 1.6 Hz, 1H), 8.21 (d, 4J ) 1.6
Hz, 1H), 8.37 (s, 2H), 8.12 (dd, J ) 7.8 Hz, J ) 1.8 Hz, 2H),
3
4
J. Org. Chem. Vol. 73, No. 16, 2008 6361

Schmidt et al.
8.06 (dd, 3J ) 8.0 Hz, 4J ) 0.7 Hz, 2H), 7.99 (dd, 3J ) 8.1 Hz, 4J
NMR (400 MHz, CDCl3) δ 8.18 (d, 3J ) 15.3 Hz, 1H), 7.76 (br s,
2H), 7.39 (d, 3J ) 15.3 Hz, 1H), 7.16 (s, 2H), 3.97 (t, 3J ) 8.2 Hz,
2H), 2.71 (t, 3J ) 8.0 Hz, 4H), 1.70 (m, 6H), 1.36 (m, 50H), 0.88
(m, 9H). HRMS (ESI) m/z calcd for C45H78N3O3 [M + H]+
708.6038, found 708.6036. Anal. Calcd for C45H77N3O3: C, 76.32;
H, 10.97; N, 5.94. Found: C, 76.33; H, 10.67; N, 5.91.
3
3
) 0.8 Hz, 2H), 7.79 (t, J ) 8.1 Hz, 2H), 7.58 (t, J ) 7.6 Hz,
1H), 7.55 (s, 2H), 2.27 (s, 4H), 1.13 (s, 18H). HRMS (ESI) m/z
calcd for C30H37N6O4 [M + H]+ 545.2871, found 545.2871. Anal.
Calcd for C30H36N6O4 ·H2O: C, 64.04; H, 6.81; N, 14.94. Found:
C, 64.12; H, 6.67; N, 15.00.
5-[2-(1,3-Dihydro-3,3-dimethyl-1-isopropyl-2H-indol-2-ylide-
ne)ethylidene]pyrimidine-2,4,6-trione (14a). To a solution of
barbituric acid (216 mg, 1.69 mmol), DMF (130 µL, 123 mg, 1.69
mmol), and 1-isopropyl-2,3,3-trimethylindoleniumiodide (500 mg,
1.52 mmol) in Ac2O (2 mL) was added KOAc (170 mg, 1.74
mmol). The reaction mixture was heated to 120 °C for 3 h. Upon
cooling to 0 °C a solid was precipitated, which was separated by
filtration. Purification of the crude product by silica gel column
chromatography with CH2Cl2/MeOH 9:1 as eluent gave pure 14a
General Procedure for the 1H NMR Titration Experiments.
The 1H NMR titration experiments were performed as constant host
titrations. To solutions of the hosts (in most cases receptors 9a or
13, concentration 1 mM) aliquots of solution of a guest (in most
cases merocyanine dyes 14a-c, concentration 5 mM) in the same
1
host solution were added and H NMR spectra (400 MHz) were
recorded after each addition. Analysis of the data was made by
nonlinear regression analysis.
General Procedure for the UV/vis Titration Experiments. For
practical reasons (detection of spectral changes in the vis region),
the role of the host and guest reversed in these experiments
1
as an orange solid (110 mg, 0.324 mmol, 21%): mp 360 °C. H
NMR (400 MHz, CDCl3) δ 8.64 (d, 3J ) 14.5 Hz, 1H), 7.82 (d, 3J
) 14.1 Hz, 1H), 7.62 (s, 1H), 7.53 (s, 1H), 7.20-7.38 (m, 4H),
1
compared to those of H NMR measurements. To the solution of
3
3
4.80 (sept, J ) 6.8 Hz, 1H), 1.71 (s, 6H), 1.66 (d, J ) 6.9 Hz,
6H). HRMS (ESI) m/z calcd for C19H21N3O3 [M + H]+ 339.1577,
found 339.1579.
a host (merocyanine dyes 14a-c, concentration 1 × 10-5 M)
aliquots of a solution of a guest (receptor 9 or 13, concentration 2
× 10-4 M) in the same host solution were added and UV/vis spectra
at 25 °C were recorded after each addition. Analysis of the data
was made by nonlinear regression analysis.
5-[2,6-Dimethyl-1-(2-ethyl)hexylpyridine-4-ylidene]pyrimidine-
2,4,6-trione (14b). To a solution of 5-(2,6-dimethylpyrane-4-
ylidene)pyrimidine-2,4,6-trione (1.00 g, 4.27 mmol) and 2-ethyl-
1-hexylamine (3.30 mL, 20.0 mmol) in EtOH (40 mL) was added
NEt3 (2.0 mL, 1.44 g, 14.2 mmol) then the solution was heated to
reflux for 20 h. Upon cooling to 0 °C a solid was precipitated,
which was filtered and recrystallized from EtOH to give 14b as a
Dipole Moment Determination. The dipole moments µg in the
ground state and the dipole moment changes upon optical excitation
∆µ ) µa - µg were determined for dyes 14a-c by electrooptical
absorption spectroscopy27 in dilute (c < 10-5 mol L-1) solutions
in 1,4-dioxane at room temperature at the Technical University of
Kaiserslautern, Germany, in the group of Prof. H.-G. Kuball.20
1
light yellow solid (1.32 g, 3.82 mmol, 90%): mp 282 °C dec. H
NMR (400 MHz, DMSO-d6) δ 8.90 (s, 2H), 7.71 (s, 2H), 4.05 (d,
3J ) 7.7 Hz, 2H), 2.54 (s, 6H), 1.79 (m, 1H), 1.34 (m, 2H),
1.15-1.26 (m, 6H), 0.82-0.88 (m, 6H). MS (EI) m/z (%) 345 (97)
[M]+. Anal. Calcd for C19H27N3O3: C, 66.06; H, 7.88; N, 12.16.
Found: C, 65.81; H, 7.86; N, 11.95.
Acknowledgment. Financial support for this work by the
Volkswagen foundation within the priority programme “Com-
plex Materials: Cooperative Projects of the Natural, Engineering
and Biosciences” is gratefully acknowledged.
5-[2-(2,6-Diundecyl-1-dodecylpyridine-4-ylidene)ethylidene]py-
rimidine-2,4,6-trione (14c). A mixture of barbituric acid (0.260
g, 2.03 mmol) and N,N-dibutylformamide (310 mg, 1.97 mmol) in
Ac2O (2 mL) was heated to 120 °C for 1 h. 1-Dodecyl-4-methyl-
2,6-diundecylpyridinium perchlorate (1.20 g, 1.80 mmol) and KOAc
(200 mg, 2.04 mmol) were added and the resulting solution was
stirred for a further 2 h at 120 °C. The solvent was removed under
reduced pressure and the residue was purified by silica gel column
chromatography with CH2Cl2/MeOH 93.5:6.5 as eluent. Recrys-
tallization of the product from acetic acid afforded pure 14c as a
Supporting Information Available: 1H NMR titration
experiments and binding constants, and 1H NMR spectra of key
compounds 9, 13, and 14a-c. This material is available free of
charge via the Internet at http://pubs.acs.org.
JO801083B
(27) (a) Liptay, W. In Excited States; Lim, E. C., Ed.; Academic Press: New
York, 1974; Vol. 1, pp 129-229. (b) Wortmann, R.; Elich, K.; Lebus, S.; Liptay,
W.; Borowicz, P.; Grabowska, A. J. Phys. Chem. 1992, 96, 9724–9730.
1
bright red solid (880 mg, 1.24 mmol, 63%): mp 168-169 °C. H
6362 J. Org. Chem. Vol. 73, No. 16, 2008