Torsionally responsive C 3-symmetric Azo dyes: Azo-hydrazone tautomerism, conformational switching, and application for chemical sensing

Article abstract of DOI:10.1021/ja105121z

An efficient triple azo coupling reaction between anilines and phloroglucinol furnished a series of C₃-symmetric molecules 7-9 supporting multiple conjugation pathways that converge at the molecular core. A combination of ¹H/¹³C NMR spectroscopy, X-ray crystallography, and density functional theory computational studies provided a coherent picture of the [n,π]-conjugated molecular core, which is best described as the tris(hydrazone) [rather than tris(azo)] tautomer stabilized by resonance-assisted hydrogen bonding. For a homologous series of compounds, an increase in the torsional angles between the planar molecular core and the peripheral aryl groups results in a systematic blue shift in the low-energy electronic transitions (7, 523 nm; 8, 505 nm; 9, 445 nm in CHCl₃) that qualitatively correlates with the shrinkage of effective conjugation through structural distortion. Similar spectral shifts could also be induced by amine substrates that interact with the intramolecular hydrogen-bonding network to trigger bond-twisting motions. Specifically, a brief exposure of a thin film of 7 to vapor samples of butyl-, hexyl-, diethyl-, and diisopropylamine resulted in a rapid and reversible color change from pink to dark-orange. Under similar conditions, however, triethylamine did not elicit any detectable color change, despite the fact that it has a significantly higher vapor pressure than n-hexylamine. These findings implicate that the hydrogen-bonding donor ability is a key requirement for the binding-induced conformational switching, which allows for direct naked-eye detection of volatile amines under ambient conditions.

Full text of DOI:10.1021/ja105121z

Published on Web 08/10/2010
Torsionally Responsive C3-Symmetric Azo Dyes:
Azo-Hydrazone Tautomerism, Conformational Switching, and
Application for Chemical Sensing
Ho Yong Lee, Xinli Song, Hyunsoo Park, Mu-Hyun Baik, and Dongwhan Lee*
Department of Chemistry, Indiana UniVersity, 800 East Kirkwood AVenue,
Bloomington, Indiana 47405
Received June 11, 2010; E-mail: dongwhan@indiana.edu
Abstract: An efficient triple azo coupling reaction between anilines and phloroglucinol furnished a series
of C3-symmetric molecules 7-9 supporting multiple conjugation pathways that converge at the molecular
core. A combination of 1H/13C NMR spectroscopy, X-ray crystallography, and density functional theory
computational studies provided a coherent picture of the [n,π]-conjugated molecular core, which is best
described as the tris(hydrazone) [rather than tris(azo)] tautomer stabilized by resonance-assisted hydrogen
bonding. For a homologous series of compounds, an increase in the torsional angles between the planar
molecular core and the peripheral aryl groups results in a systematic blue shift in the low-energy electronic
transitions (7, 523 nm; 8, 505 nm; 9, 445 nm in CHCl3) that qualitatively correlates with the shrinkage of
effective conjugation through structural distortion. Similar spectral shifts could also be induced by amine
substrates that interact with the intramolecular hydrogen-bonding network to trigger bond-twisting motions.
Specifically, a brief exposure of a thin film of 7 to vapor samples of butyl-, hexyl-, diethyl-, and
diisopropylamine resulted in a rapid and reversible color change from pink to dark-orange. Under similar
conditions, however, triethylamine did not elicit any detectable color change, despite the fact that it has a
significantly higher vapor pressure than n-hexylamine. These findings implicate that the hydrogen-bonding
donor ability is a key requirement for the binding-induced conformational switching, which allows for direct
naked-eye detection of volatile amines under ambient conditions.
or electrochemical signal output.2,10-12 Continuing challenges
in such efforts lie in the invention and elaboration of new
functional-group-rich π-conjugated platforms that can be (i)
Introduction
Conjugation pathways supported by rigid π-skeletons can be
modified by either covalent or noncovalent interactions, thereby
offering opportunities to tune the optoelectronic properties
inherent in extended electronic structures.1-10 An increasing
number of sensory systems have now been built on this
principle, in which binding-induced conformational change
along the π-backbone is tightly coupled to changes in the optical
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A R T I C L E S
Lee et al.
Scheme 1. Conformational Switching between the Folded and
Unfolded Conformations of Tris(N-salicylideneamine)
Scheme 2. Synthesis of C3-Symmetric Chromophores 1 and 4 [as
the 4H ()Hydrazone) or 4A ()Azo) Tautomer] by Triple Schiff Base
Condensation (for 1) and Triple Azo Coupling (for 4)
readily prepared from simple building blocks and (ii) easily
modified via orthogonal synthetic operations on simple precursors.
We have previously reported a facile route for constructing
tris(N-salicylideneamine)13,14-based conjugated chemical struc-
tures (Scheme 1).15-22 The C3-symmetric molecular core of the
prototypical molecule 1 supports branched two-dimensional (2D)
conjugation that radially extends to three aryl groups. In addition
to modulation of the degree of conjugation between the [n,π]-
conjugated core and the peripheral π extensions, torsional
motions about the C-N bonds around the threefold-symmetric
molecular core control the excitation and de-excitation pathways
of these conformationally nonrigid fluorophores.11
Taking advantage of this structure-property relationship, we
have shown that an intramolecular hydrogen-bonding network
can be introduced to the peripheral aryl groups in 2 in order to
drive the two-state switching between the “folded” conformer
2F and the “unfolded” conformer 2U (Scheme 1). External
stimuli such as solvation, binding of an anion, or thermal energy
thus elicit a reversible change in fluorescence and/or circular
dichroism (for chiral derivatives).18-22
condensation reaction between 1,3,5-triformylphloroglucinol and
primary amines. A close inspection of the keto-enamine
molecular core of 1 logically suggests that a conceptually related
C3-symmetric platform 4 should readily be constructed by a
triple azo coupling onto phloroglucinol (3) to formally replace
the three CH-NH fragments in 1 with essentially isostructural
N-NH units. In fact, the preparation of the parent “tris(phe-
nylazo)phloroglucinol” 4 (Scheme 2; initially proposed as the
azo tautomer 4A) was described by Perkin as early as in 1897,23
but only a handful of reports on its characterization have
appeared since then.24-29
As shown in Scheme 2, the parent tris(N-salicylideneamine)
system 1 can readily be constructed by a triple Schiff base
(13) (a) Chong, J. H.; Sauer, M.; Patrick, B. O.; MacLachlan, M. J. Org.
Lett. 2003, 5, 3823–3826. (b) Sauer, M.; Yeung, C.; Chong, J. H.;
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Achalkumar, A. S.; Rao, D. S. S.; Prasad, S. K. J. Org. Chem. 2007,
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Yelamaggad, C. V.; Achalkumar, A. S.; Rao, D. S. S.; Prasad, S. K.
J. Org. Chem. 2009, 74, 3168–3171.
Intriguingly, the core tautomerism of 4 remains ambiguous
even today, more than a century after its initial synthesis. The
term “phenylazo”, which has typically been used to describe 4
(23) Perkin, A. G. J. Chem. Soc., Trans. 1897, 71, 1154–1156.
(24) Parini, V. P.; Gudvilovich, I. V.; Sorokin, A. V. IzV. Akad. Nauk SSSR
1966, 572–575.
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1967, 2635–2640.
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W.; Ringsdorf, H.; Sawodny, M.; Urban, C. Thin Solid Films 1992,
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11732–11733.
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(29) A particular subclass of this structural motif having sugar-appended
phenyl groups, known as Yariv reagents, have found practical
applications in biochemical assays as multivalent dyes for staining or
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Torsionally Responsive C3-Symmetric Azo Dyes
A R T I C L E S
Scheme 3. Synthetic Routes to 7-9a
and its derivatives,23,26,29,30 might adequately denote their
chemical origin (from azo coupling) but incorrectly depicts the
true chemical structure (see below). As shown in Scheme 2,
the [n,π]-conjugated core of 4 can be described as either the
tris(keto-hydrazone) (commonly denoted as “hydrazone”; 4H)
or tris(azo-enol) (commonly denoted as “azo”; 4A) form.
Studies in the 1960′s using UV-vis spectroscopy proposed an
equilibrium between 4H and 4A that was based on qualitative
comparison with other azo-based chromophores.24 A similar
interpretation was made on the basis of the IR data for 4, which
display what had been considered to be the signatures of NdN,
CdN, and CdO bond-stretching frequencies.25 This assignment,
however, was later challenged by solution 1H NMR studies on
a derivative of 4,27 in which the presence of two sets of proton
resonances was explained by invoking two slowly exchanging
tris(hydrazone) isomers that have restricted rotation around the
C-N bonds (see below). The only crystallographically char-
acterized example of 4 is its deprotonated form 53- (eq 1), which
supports an M12L8-type cluster of copper(II).28 As anticipated,
the negative charge associated with the N,O-chelate is localized
on the more electronegative oxygen atom, shifting the equilib-
rium toward the azo-enolate tautomer (5A3-) rather than the
keto-hydrazonate tautomer (5H3-) (eq 1). Whether the same
trend prevails for the neutral 4H versus 4A (Scheme 2) is an
intriguing question, for which no structural evidence has been
reported to date.
a Reaction conditions: (a) NaOH (2 M) in H2O/MeOH, 0 °C. (b) (i) HCl
(2 M) in H2O/MeOH, 0 °C; (ii) NaNO2, H2O, 0 °C.
aryls to profoundly impact the conjugation pathways; and (iii)
such torsion-dependent shifts in electronic transitions can further
be exploited for the colorimetric sensing of amine vapors. The
details of our findings are described in the following sections.
Azo dyes represent the most abundant class among com-
mercial organic colorants, accounting for nearly 60% of the dyes
currently available. In particular, the azo and hydrazone tau-
tomers of hydroxyl azo compounds have been extensively
studied, as the tautomeric state of such [n,π]-conjugated
materials is directly related to the color profile.31-33 Their rich
photochemistry and the feasibility of modulating their optical
properties through conformational switching have provided
further impetus for our investigation of the previously underuti-
lized azo-based chromophore 4. Through a combination of
experimental and theoretical studies, we have found that (i) the
hydrogen-bonded molecular core of the formally “tris(azo)”
phloroglucinol is best described as the keto-hydrazone rather
than the enol-azo tautomer; (ii) the periphery of this robust
C3-symmetric [n,π] conjugation can be functionalized with bulky
Results and Discussion
Synthesis and Tautomerism in Solution. As shown in Scheme
3, efficient triple azo coupling reactions between 3 and aniline
derivatives furnished compounds 7-9 as bright-red solids (7,
81%; 8, 34%; 9, 82%) after purification by column chroma-
tography. The 1H NMR spectra of 7-9 in CDCl3 (T ) 298 K)
display simple spectral patterns indicative of high molecular
symmetry (Figure S1 in the Supporting Information). Notably,
the significantly downfield-shifted resonances at >16 ppm
suggest the presence of protons that engage in strong hydrogen
bonding (Figure 1). This information alone, however, could not
be used to distinguish between the azo and hydrazone tautomers
(Scheme 2), as both have D-H· · ·A (D ) hydrogen-bond
donor; A ) hydrogen-bond acceptor) arrays disposed with
threefold symmetry at the molecular core.
An initial clue for assigning the tautomeric state was provided
by the H NMR spectra obtained in DMSO-d6. As shown in
(30) (a) Pauling, L.; Pressman, D.; Campbell, D. H.; Ikeda, C.; Ikawa, M.
J. Am. Chem. Soc. 1942, 64, 2994–3003. (b) Pressman, D.; Swingle,
S. M.; Grossberg, A. L.; Pauling, L. J. Am. Chem. Soc. 1944, 66,
1731–1738.
1
Figure 1d, 7 in DMSO-d6 revealed the presence of two sets of
downfield-shifted signals that reflect the presence of C3h and
Cs isomers in a ratio of ∼5:1 (Scheme 4). While the low energy
barrier for rotation around the C-N single bonds in the azo
tautomer would give rise to a single set of resonances as a
population-averaged signal, the restricted rotation around the
CdN double bonds in the hydrazone form would lead to two
distinctive geometric isomers, one with local C3h symmetry and
(31) Christie, R. M. Colour Chemistry; Royal Society of Chemistry:
Cambridge, U.K., 2001.
(32) Zollinger, H. Color Chemistry: Syntheses, Properties, and Applications
of Organic Dyes and Pigments, 3rd ed.; VHCA: Zu¨rich, Switzerland,
2003.
(33) Herbst, W.; Hunger, K. Industrial Organic Pigments: Production,
Properties, Applications, 3rd ed.; Wiley-VCH: Weinheim, Germany,
2004.
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A R T I C L E S
Lee et al.
Figure 2. Partial 13C NMR spectra of (a) 7, (b) 8, and (c) 9 in CDCl3 at
T ) 298 K. The corresponding spectrum of 7 in DMSO-d6 is shown in (d),
in which peaks are assigned to two isomers of local C3h (0) and Cs (b)
symmetry (see Scheme 4).
Figure 1. Partial 1H NMR spectra of (a) 7, (b) 8, and (c) 9 in CDCl3 at T
) 298 K. The corresponding spectrum of 7 in DMSO-d6 is shown in (d),
in which peaks are assigned to two isomers of local C3h (0) and Cs (b)
symmetry (see Scheme 4).
supported the dominance of the hydrazone tautomer with the
characteristic carbonyl carbon resonance at 178 ppm.44 This
parameter is close to the value of 174 ppm obtained by time-
dependent density functional theory (TD-DFT) studies of the
model compound 7′H (Scheme 5; see below). In DMSO-d6, a
total of four carbonyl resonances at 175-178 ppm were
observed for 7 (Figure 2d), again confirming the presence of
two slowly exchanging isomeric forms of the tris(hydrazone)
tautomer (Scheme 4). Apparently, the hydrogen-bonding solvent
DMSO raises the kinetic barrier for their structural intercon-
version on the NMR time scale. Over the temperature range
from -40 to 50 °C, the N-H resonance of 7 at 16.4 ppm (in
CDCl3) remains essentially unchanged (Figure S2 in the
Supporting Information). The characteristic carbon resonance
at 178 ppm is also invariant under similar conditions (Figure
S3 in the Supporting Information). These findings indicate that
7 mainly exists as the hydrazone form rather than as an
equilibrium mixture of several tautomeric species.
Core Tautomerism: Computational Studies. The experimen-
tally determined preference for the tris(hydrazone) rather than
the tris(azo) tautomers of 7-9 in solution prompted theoretical
investigations using DFT calculations. As highlighted in Scheme
2, the valence-bond description of the core tautomerism suggests
that a cyclic array of keto-hydrazone fragments should formally
destroy the aromaticity of the benzene ring at the core and thus
be energetically disfavorable. We wished to gain a quantitative
understanding of this seemingly counterintuitive bond rear-
rangement pattern resulting from triple azo coupling. DFT
calculations on 7 and 8 were carried out using the simplified
model compounds 7′ (Scheme 5) and 4 (Scheme 2), in which
the tert-butyl groups on the aniline rings and the gem-dimethyl
groups on the wing-tip tertiary alcohol fragments were replaced
by hydrogen atoms to render the calculations computationally
tractable. We expect these slight simplifications to have only a
minor impact on the relative energetics of the two tautomers.
As summarized in Table 1, the difference between the
solution-phase free energies of the two tautomeric forms was
consistently large enough in favor of the tris(hydrazone) over
the tris(azo) tautomer to justify the dominating presence of the
former in an equilibrium situation. This general trend is
maintained regardless of the structure of the aryl groups attached
to the C3-symmetric {C6O3(N2H)3} core. The hydrazone tau-
tomer 7′H is 15.93 kcal mol-1 lower in free energy than the azo
tautomer 7′A in CHCl3. For 4 and 9, 4H and 9H are preferred
over 4A and 9A by 17.43 and 11.87 kcal mol-1, respectively. In
more closely examining the structures of the two tautomers,
subtle structural differences with potentially significant energetic
consequences can be recognized.
Scheme 4. Azo versus Hydrazone Tautomerism and Geometric
Isomerism of the Hydrazone Tautomer
the other with Cs symmetry, as shown in Scheme 4.27 A total
of four unique N-H resonances were thus anticipated for the
slowly exchanging isomers and were indeed observed experi-
mentally (Figure 1d).
This interpretation is further supported by similar observations
made for related tris(N-salicylideneamine) derivatives, in which
the coexistence of two slowly interconverting isomers having
C3h and Cs symmetry with two independent sets of Cvinyl-H
and Nenamine-H resonances is consistent with the keto-enamine
rather than the enol-imine description of the core.13,14,17
A large number of azo dyes have a hydroxyl group at the
orthoposition,whichnotonlypreventstrans-to-cisisomerization34,35
but also stabilizes the hydrazone form through resonance-
assisted hydrogen bonding (RAHB).36-41 For such constructs,
the 13C chemical shift has widely been used to assign the
tautomeric state, since the phenolic and carbonyl carbon atoms
have distinctively different resonances.42-44 The 13C NMR
spectra of 7-9 obtained in CDCl3 at T ) 298 K (Figure 2)
(34) Natansohn, A.; Rochon, P. Chem. ReV. 2002, 102, 4139–4175.
(35) Kumar, G. S.; Neckers, D. C. Chem. ReV. 1989, 89, 1915–1925.
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Torsionally Responsive C3-Symmetric Azo Dyes
A R T I C L E S
Scheme 5. Chemical Structures of the DFT Models as Hydrazone
with the interaction strength being greater in the resonance-
stabilized 4A tautomer. As a consequence, the vibrational modes
involving out-of-plane distortions of the peripheral moiety are
shifted to higher energies in 4A relative to 4H, which in turn
gives rise to a notable vibrational entropy penalty (see the
Supporting Information) of nearly 2.5 kcal mol-1 at room
temperature in the gas phase, increasing the energetic preference
to 13.14 kcal mol-1. In 7′ and 9, however, the nonplanar
arrangement weakens the π resonance between the peripheral
and core moieties, so the entropic gain of having weaker C-O
bonds dominates, affording an entropic preference for 7′A and
9A over their enthalpically preferred tautomers. The energetic
preference for the tris(hydrazone) form is thus lessened to 15.43
and 9.86 kcal mol-1, respectively, on the gas-phase free-energy
surface. Whereas these are small effects, the sign of the
correction amplifies the overall energetic impact, as demon-
strated in the enthalpic and free-energy differences for the two
tautomers 7′ and 4. In the former, the enthalpic energy difference
of 17.09 kcal mol-1 becomes 15.43 kcal mol-1 in gas-phase
free energy, whereas in the latter case, the energy difference
increases from 10.73 to 13.14 kcal mol-1. Since the entropic
differences are sensitive to the temperature, these intuitively
understandable energy trends provide a rational design element
that we intend to exploit further in future work. The impact of
solvation is easy to understand by recognizing that in 4 the
hydrazone/azo moieties are exposed to solvents, while they are
shielded from solvent access to a certain degree in 7′ and 9.
Consequently, a greater differential solvation energy is computed
for 4 than for the functionalized analogues.
(H) or Azo (A) Tautomers
Table 1. Relative Energies (in kcal mol-1) of the Tris(Hydrazone)
Tautomers Referenced to the Corresponding Tris(Azo) Tautomersa
∆G
∆Hgas () ∆E + ∆ZPE)
gas phase
in CHCl3
7′
4
9
17.09
10.73
11.93
15.43
13.14
9.86
15.93
17.43
11.87
a ∆Hgas ) Htris(azo) - Htris(hydrazone) and ∆G ) Gtris(azo) - Gtris(hydrazone)
.
Lastly, our DFT model demonstrates that 7′H has an additional
array of hydrogen bonds connecting the OH groups on the
ethynyl-extended wing tips of the peripheral aryl groups.45 In
addition to enhancing the conformational rigidity, the
Ohydroxyl-H· · ·Ohydroxyl-H· · ·Oketone cascade in 7′H (Figure 3b)
should further stabilize the molecule relative to the alternative
tautomer 7′A having the Ohydroxyl-H· · ·Ohydroxyl-H· · ·Ohydroxyl-H
network (Figure 3b). In support of this notion, the O · · ·O
distance between the wing-tip OH group and the hydrogen-
bonded oxygen atom at the molecular core is significantly
shorter in 7′H (2.790 Å) than in 7′A (2.891 Å) (Figure 3b). As
anticipated, the ketone oxygen atom in 7′H functions as a better
hydrogen-bonding acceptor than the hydroxyl oxygen atom in
7′A and thus engages in a stronger hydrogen bond with the O-H
group. These findings imply that secondary interactions with
remotely located functional groups could further influence the
energetics of tautomerization occurring at the molecular core.
This intuitive interpretation is supported by the significantly
larger energy difference (∆Hgas) between 7′H and 7′A relative
to those for the 4H-4A and 9H-9A pairs, which lack such
interactions (Table 1).
Core Tautomerism: X-ray Crystallography. Direct experi-
mental evidence to validate the DFT studies was obtained by
single-crystal X-ray diffraction on 7 at T ) 120 K. As shown
in Figure 4, the planar {C6O3(N2H)3} core of 7, with a mean
deviation of 0.0128 Å from the least-squares plane, is supported
by a cyclic bonding network that is arranged in a pseudo-C3-
symmetric fashion. The short interatomic distances between N
and O [N(2) · · · O(2), 2.580(2) Å; N(4) · · · O(3), 2.519(3);
N(6)· · ·O(1), 2.592(2) Å] indicate that they are involved in
strong hydrogen bonds assisted by resonance36-41 in a manner
similar to the situation in structurally characterized tris(N-
salicylideneamine)s (Schemes 1 and 2).13,16,18,20
Figure 3. (a) Capped-stick representation of the DFT (B3LYP/6-31G**)-
optimized geometries of models 7′H, 4H, and 9H. (b) Close-up view showing
hydrogen bonds (dotted red lines) in 7′H (left) and 7′A (right) and O· · ·O
interatomic distances (see Table 2 for a list of relevant geometric
parameters).
First, 4 maintains planar symmetry in both tautomers, whereas
the steric demands of the peripheral decoration force the other
two systems to deviate significantly from an overall planar
geometry (Figure 3). The phenyl rings in 4 can therefore
maintain a relatively strong π conjugation in both tautomers,
9
J. AM. CHEM. SOC. VOL. 132, NO. 34, 2010 12137

A R T I C L E S
Lee et al.
Table 2. Selected Bond Distances (in Å) from the X-ray Structure
of 7 and the Corresponding Parameters in the DFT Models 7′H
and 7′A
7
7′H
7′A
N(1)-N(2)
N(3)-N(4)
N(5)-N(6)
O(1)-C(6)
O(2)-C(2)
O(3)-C(4)
N(1)-C(1)
N(3)-C(3)
N(5)-C(5)
1.298(3)
1.295(2)
1.295(3)
1.248(3)
1.244(3)
1.245(3)
1.326(3)
1.341(3)
1.332(3)
1.295a
1.275a
1.254a
1.337a
1.322a
1.386a
a Calculated for the C3-symmetric geometry.
Figure 5. Difference Fourier map at 120(2) K computed in the mean plane
of the {C6O3(N2H)3} core of 7 after refinement was carried out with the
hydrogen atoms excluded.46
Scheme 6. Azo (10A) versus Hydrazone (10H) Tautomer
Equilibrium of 1-Phenylazo-2-hydroxynaphthol 10
Figure 4. X-ray structure of 7 as ORTEP diagrams with thermal ellipsoids
at 50% probability in which the gem-dimethyl groups have been omitted
for clarity: (a) top view; (b) side view. (c) Close-up view showing hydrogen
bonds (dotted red lines) and selected interatomic distances (see Table 3 for
a full list).
that the H atoms are located near the N atom rather than the O
atom, which again is consistent with the hydrazone tautomer
description.
As is evident from Table 2, the N-N, C-O, and C-N bond
lengths are sensitive to the tautomeric state. In order to evaluate
our own experimental findings against a larger set of structurally
characterized azo vs hydrazone tautomers, we conducted a
Cambridge Structural Database (CSD)47 search on 1-phenylazo-
2-hydroxynaphthol derivatives 10 (Scheme 6). This azo-based
chromophore has been studied extensively because it is the basic
structural unit of Sudan dyes, which are popular commercial
organic colorants.42,48-52 In addition, comprehensive studies of
10 using a combination of experimental and theoretical tools
have significantly aided our understanding of RAHB.37,38,53
On the basis of a total of 49 reported structures,54 plots of
C-O versus C-N bond distances (Figure 6a) and C-O versus
N-N bond distances (Figure 6b) were constructed for the
systems that were assigned as the hydrazone tautomer 10H or a
A careful analysis of the crystallographically determined
N-N, C-N, and C-O bond distances defining the six-
membered “chelate” structure revealed that the bond metrics
are comparable to those of the DFT model 7′H rather than the
alternative tautomer 7′A (Table 2). In particular, the CdO
double-bond character of the molecular core of 7 is evident in
the bond distances of 1.244(3)-1.248(3) Å, which are close to
the calculated parameter of 1.254 Å for the tris(hydrazone) DFT
model 7′H. In 7′A, the corresponding C-O distance is signifi-
cantly elongated to 1.322 Å, which clearly reflects the azo-enol
character (Scheme 5 and Figure 3). In support of this notion,
the difference electron density map of 7 (Figure 5) revealed
(45) In a manner similar to the σ-bond cooperativity that is typically
observed in extended networks of alcohols and phenols, this arrange-
ment should polarize the participating O-H bonds and further
strengthen the hydrogen bond.
(46) WinGX, version 1.70.01: Farrugia, L. J. J. Appl. Crystallogr. 1999,
32, 837–838.
(47) CSD, version 5.31 (last updates Feb 2010).
9
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Torsionally Responsive C3-Symmetric Azo Dyes
A R T I C L E S
Table 3. Crystallographically Determined Interatomic Distances of
Hydrogen Bonds Involving O-H Groups in 7a
D-H· · ·A
D· · ·A distance (Å)
D-H· · ·A angle (deg)
O(4)-H(4A)· · ·O(7)
O(5)-H(5A)· · ·O(1)
O(9)-H(9A)· · ·O(3)
O(7)-H(7A)· · ·O(2)
O(6)-H(6A)· · ·O(9)
2.783(3)
2.998(3)
2.896(3)
2.716(2)
2.851(4)
178.3
166.9
176.8
148.4
170.4
a D ) hydrogen-bond donor; A ) hydrogen-bond acceptor.
of 1.333(6)-1.385(4) Å, while their C-O and C-N bond
distances are comparable to those of others, except in the case
of 10d (Figure 6b).56-59 Such elongated N-N bonds have
occasionally been described as evidence for the hydrazone
tautomer.42,57,60,61 According to previous reports,43,62,63 both 10b
and 10e exist mainly as the hydrazone tautomers in solution,
but the N-N bond distance in 10b [1.345(7) Å] is significantly
longer than that [1.307(2) Å]64 in 10e. Increasing the number
of nitro substituents, as in 10d, results in a further lengthening
of N-N bond to 1.385(4) Å. We suspect that not only the
tautomeric state but also the electron-withdrawing effects of the
nitro group might contribute to the lengthening of the N-N
bond in 10a-d. The use of the N-N bond distance as a sole
criterion for assigning the azo-hydrazone tautomer state should
thus be exercised with caution.
Figure 6. Plots of (a) C-O vs C-N and (b) C-O vs N-N bond distances.
Data obtained from the CSD search are represented as triangles; blue
triangles represent data for compounds 10a-d (see Figure 7). Red squares
represent data from the X-ray structure of 7.
Conformational Switching Assisted by Hydrogen Bonds.
X-ray crystallographic studies of 7 also revealed that its wing-
tip alcohol groups participate in an extensive intramolecular
hydrogen-bonding network, such as O(4)-H(4)· · ·O(7)-H(7)
· · ·O(2), which converges at the tris(hydrazone) molecular core
(Figure 4). The O· · ·O interatomic distances of the groups
involved in such hydrogen bonds are listed in Table 3.
Notably, such pairwise contacts between terminal O-H groups
bring the ethynyl-extended wing-tips into close proximity, thereby
flattening the entire molecule, which has an average dihedral angle
of τ ) 23° between the molecular core and the peripheral aryl
Figure 7. Chemical structures and crystallographically determined N-N
bond distances of selected 1-phenylazo-2-hydroxynaphthols as the hydrazone
tautomers.
fast-exchanging mixture with the azo tautomer 10A having a
preference for 10H. Similar empirical correlations were previ-
ously made for a larger set of data obtained from azo-hydrazone
tautomers.55 In our analysis, average bond distances of 1.305,
1.264, and 1.335 Å were determined for the N-N, C-O, and
C-N bonds. The metric parameters determined experimentally
for 7 and its DFT model 7′H (Table 2) are comparable to these
values and fit within the range anticipated for the hydrazone
structure (Figure 6).
rings. The functional role of such Ohydroxyl-H· · ·Ohydroxyl
-
H· · ·Oketone cascades was previously established for structurally
analogous tris(N-salicylideneamine)s,15,18-22 in which structural
interconversion between the folded and unfolded conformations
(Scheme 1) could be driven by the assembly and disassembly of
such noncovalent contacts. A drastic change in the number of
torsional bonds between the two conformers profoundly impacts
the emission properties through opening and closing of nonradiative
decay channels.65
During our comparative structural analysis, we noted that a
series of 1-arylazo-2-hydroxynaphthols containing nitro groups
(10a-d; Figure 7) have unusually long N-N bond distances
In the solid state, however, one of the wing-tip OH groups
in 7 is twisted away from the molecular core to engage in a
weak intermolecular O-H· · ·O hydrogen bond (O · · ·O, 3.134
(48) Burawoy, A.; Salem, A. G.; Thompson, A. R. J. Chem. Soc. 1952,
4793–4798.
(49) Simov, D.; Stojanov, S. J. Mol. Struct. 1973, 19, 255–274.
(50) Ball, P.; Nichols, C. H. Dyes Pigm. 1982, 3, 5–26.
(51) Antonov, L.; Stoyanov, S.; Stoyanova, T. Dyes Pigm. 1995, 27, 133–
142.
(56) Grainger, C. T.; McConnell, J. F. Acta Crystallogr. 1969, B25, 1962–
1970.
(57) Guggenberger, L. J.; Teufer, G. Acta Crystallogr. 1975, B31, 785–
790.
¨
(52) Ozen, A. S.; Doruker, P.; Aviyente, V. J. Phys. Chem. A 2007, 111,
(58) Schmidt, M. V.; Buchsbaum, C.; Schnorr, J. M.; Hofman, D. W. M.;
Ermrich, M. Z. Kristallogr. 2007, 222, 30–33.
(59) Yatsenko, A. V.; Paseshnichenko, K. A.; Chernyshev, V. V.; Schenk,
H. Acta Crystallogr. 2001, E57, o1151–o1153.
(60) Pendergrass, D. B.; Paul, I. C.; Curtin, D. Y. J. Am. Chem. Soc. 1972,
94, 8730–8737.
13506–13514.
(53) Gilli, P.; Bertolasi, V.; Pretto, L.; Gilli, G. J. Mol. Struct. 2006, 790,
40–49.
(54) CSD codes: BEKHAB, BIHNUC, CABWAE, CICCUN, DEHMIN,
DEHMOT, DEHMUZ, DEHNAG, DEHNEK, DEHNIO, DEHNOU,
DEHNUA, DEHPAI, DOTQIN, DUNION, HIQZOX, JARPEX,
JATJIX, JAYREH, KAQSAW, KIBJOU, LEMQID, LEZHIH,
LEZHON, MAMMEU, MAMMIY, NQNCPH, OGUWES, OGUXAP,
OLOCAT, PAHGUB, PAMBOO, POYSUS, POYTAZ, POYTED,
SCNPHO, SIWVUP, SOQQIY, VEHXIP, VEHXOV, WIKWOC,
WIKWUI, WIKXAP, WIKXET, ZUCQET, ZUCQIX, ZUCQOD,
ZUCQUJ, ZUCRAQ.
(61) Schmidt, M. U.; Bru¨ning, J.; Wirth, D.; Botle, M. Acta Crystallogr.
2008, C64, o474–o477.
(62) Berrie, A. H.; Hampson, P.; Longworth, S. W.; Mathias, A. J. Chem.
Soc. B 1968, 1308–1310.
(63) Kelemen, J.; Moss, S.; Glitsch, S. Dyes Pigm. 1984, 5, 83–108.
(64) Yu, Y.; Qian, K. Acta Crystallogr. 2009, E65, o2033.
(65) Turro, N. J. Modern Molecular Photochemistry; University Science
Books: Sausalito, CA, 1991.
(55) Kelemen, J.; Korma´ny, G.; Rihs, G. Dyes Pigm. 1982, 3, 249–271.
9
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A R T I C L E S
Lee et al.
Scheme 7. Temperature-Dependent Structural Folding and
Unfolding
is reflected in the deshielding of the O-H protons and
systematic downfield shifts.
The temperature-dependent chemical shift of 7 was subse-
quently analyzed using a δobs versus 1/T plot (Figure 8b) on
the basis of the model shown in Scheme 7. With the δ7U value
of 2.02 ppm obtained from initial fitting, which is close to the
non-hydrogen-bonded O-H proton resonance of the free aniline
6 at 2.16 ppm, further nonlinear regression was carried out to
provide the values δ7F ) 6.31 ( 0.01 ppm, ∆H ) 2.43 ( 0.04
kcal mol-1, and ∆S ) 4.6 ( 0.1 cal mol-1 K-1. These
parameters are comparable to those obtained for a tris(N-
salicylideneamine)-based system (∆H ) 2.2 ( 0.1 kcal mol-1
;
∆S ) 4.2 ( 0.1 cal mol-1 K-1)22 and confirmed the endothermic
nature of structural unfolding (positive ∆H). We note that the
hydrogen bonding in the tris(hydrazone) molecular core of 7 is
unaffected under these condition (Figures S2 and S3 in the
Supporting Information).
Figure 8. (a) Partial 1H NMR spectra (400 MHz) of 7 in CDCl3 (10 mM)
showing the O-H proton resonance as a function of temperature from -40
to +50 °C. (b) Plot of δobs(O-H) vs 1/T (b) overlaid with the fit (gray
line). See the text for the values of the thermodynamic parameters ∆H and
∆S derived from nonlinear curve fitting and Scheme 7 for the model used.
Photophysical Consequences of Bond Twisting. In CHCl3 at
T ) 25 °C, compounds 7-9 display intense electronic transitions
as two broad peaks that are separated by ∆λ ) 100-127 nm
(Figure 9). In the case of 4, such features were previously
assigned as individual contributions from the azo (for the
shorter-wavelength transition) and hydrazone (for the longer-
wavelength transition) tautomers, respectively.24 Our solution
NMR studies, DFT calculations, and single-crystal X-ray
analysis described in previous sections, however, strongly
suggest that both absorption bands arise from the hydrazone
tautomer, which dominates the solution population.
Å; Figure S4 in the Supporting Information) to a neighboring
molecule in the lattice. Such a structural deviation from ideal
threefold symmetry arises from solid-state packing interactions
that promote intermolecular contacts, which are unlikely to occur
in solution phase. In support of this notion, the 1H NMR
spectrum of 7 in CDCl3 at T ) 298 K shows a single sharp
O-H proton resonance of the tertiary alcohols at 5.72 ppm
(Figure 8a) that is significantly downfield-shifted relative to that
of 6 (2.16 ppm) (Scheme 3). Within the 2-36 mM concentration
range, the O-H proton resonances of 7 remain essentially
invariant, which is consistent with their involvement in an
intramolecular hydrogen bonding network, as supported by the
DFT-optimized geometry of the structure (Figure 3).
Intriguingly, the 2,6-substituents on the peripheral aryl rings
profoundly impact the photophysical properties of the homolo-
gous series of tris(hydrazone) chromophores 7-9. As shown
in Figure 9, a systematic blue shift in electronic absorption was
observed along the series 7 f 8 f 9. This trend nicely correlates
with an increase in the torsional angle (τ) between the planar
conjugated tris(hydrazone) core and the peripheral aryl groups.
As shown in Figures 3 and 4, the O-H· · ·O-H hydrogen
bonding between the ethynylene-extended 2,6-substituents on
the aniline rings promotes structural collapse with the relatively
small dihedral angles of τ ) 24° in the DFT model 7′H and τ
) 19-25° in structurally characterized 7. On the other hand,
steric constraints imposed by the bulky 2,6-diisopropyl substit-
uents in 9 enforce large dihedral angles of τ ) 54-65° (Figure
3). Such a conformation effectively minimizes undesired van
der Waals contacts, as previously observed in the X-ray structure
of a similar tris(N-salicylideneamine) derivative.17 Sterically
“neutral” compound 8, having neither attractive (as in 7) nor
As shown in Figure 8a, variable-temperature (VT) 1H NMR
studies on 7 from +50 to -40 °C revealed a systematic
downfield shift of the O-H proton resonance from 5.49 to 6.09
ppm with decreasing temperature. This behavior can best be
explained by a fast exchange between the folded (7F) and
unfolded (7U) conformers, which gives rise to a population-
averaged δobs value (Scheme 7).22 This experimental observable
could be fitted using an idealized two-state model66 with
contributions of δ7F (from 7F) and δ7U (from 7U), which exist
in mole fractions of x and 1 - x, respectively, in solution. In
this model, the increasing population of the folded conformation
7F through reinforced hydrogen bonding at lower temperatures
(66) The cooperative nature of structural folding (see ref 21) would cause
the system to approximate the “all-or-nothing” situation as depicted
in Scheme 7, but partially folded/unfolded conformations deviating
from the ideal threefold symmetry might also contribute to δobs
.
9
12140 J. AM. CHEM. SOC. VOL. 132, NO. 34, 2010

Torsionally Responsive C3-Symmetric Azo Dyes
A R T I C L E S
Figure 9. (a) UV-vis spectra of 7 (red), 8 (green), and 9 (blue) in CHCl3
at 25 °C. (b) Normalized UV-vis spectra of 7 (red), 8 (green), and 9 (blue)
for comparison of structure-dependent spectral shifts. (c) Photographic
images of CHCl3 solutions of 7-9 (concentration ) 0.02 mM) and
schematic representations of the corresponding molecular structures. Steric
crowding enforces deconjugation between the molecular core and the
peripheral aryls in 9, while hydrogen-bonding-assisted planarization pro-
motes long-range electronic conjugation in 7.
Figure 10. (a) UV-vis spectra of 7 in CHCl3 (red) and DMSO (blue). (b)
Normalized UV-vis spectra of 7 in CHCl3 (red) and DMSO (blue); the
insets show photographic images of the corresponding solutions (concentra-
tion ) 0.02 mM). (c) Normalized UV-vis spectra of 8 in CHCl3 (red) and
DMSO (blue).
repulsive (as in 9) steric bias, is thus anticipated to sample a
wider window of τ values without significant energetic gain or
penalty.
Table 4. UV-Vis Data for 7 and 8 in Selected Solvents (T ) 298
K)
An intuitive particle-in-a-box model would thus suggest that
a progressive shrinkage in the electronic conjugation along the
series 7 f 8 f 9 would translate into increasing energy gaps
between the molecular orbitals (MOs) involved in the electronic
transition and therefore shift the UV-vis absorption to shorter
wavelengths (Figure 9).15 Because of a large shift in the longer-
wavelength transitions (7, λmax ) 523 nm; 8, λmax ) 505 nm; 9,
λmax ) 445 nm), the color difference could be detected even by
the naked eye (Figure 9c).
compound
solvent
λmax (nm)
7
hexane
toluene
CHCl3
THF
acetone
MeCN
MeOH
DMSO
CHCl3
MeOH
DMSO
517, 391
523, 395
523, 396
516, 386
506, 384
496, 385
506, 379
502, 373
505, 392
498, 386
499, 382
8
Solvent-Driven Conformational Switching. The active role
played by the intramolecular hydrogen bonds in the structural
interconversion (Scheme 7) prompted the investigation of
molecule-solvent interactions in conformational switching. An
additional point of consideration within this context was whether
the tautomeric equilibrium of the tris(hydrazone) molecular core
would also shift in response to external stimuli.43,48,67-69
As shown in Figure 10c, the normalized UV-vis spectra of
8 in DMSO and CHCl3 are essentially superimposable, indicat-
ing that the electronic structure of the tris(hydrazone) core
remains largely unperturbed upon changes in solvent polarity
or hydrogen-bonding ability. This observation is also consistent
with the 1H and 13C NMR data (Figures 1 and 2), which
confirmed the solvent-invariant nature of the tris(hydrazone)
tautomer.
In contrast, the UV-vis spectra of 7 in hydrogen-bonding
solvents such as DMSO and MeOH show significant (∆λ ≈ 20
nm) blue shifts relative to those taken in non-hydrogen-bonding
solvents such as toluene and CHCl3 (Figure 10a,b; see Table 4
for a summary of the UV-vis spectral data of 7 and 8 in
representative solvents). This observation can be rationalized
by the O-H· · ·(solvent)n interactions in 7 that would compete
with the intramolecular O-H· · ·O-H hydrogen bonds to trigger
structural unfolding (Scheme 8).
(67) Reeves, R. L.; Kaiser, R. S. J. Org. Chem. 1970, 35, 3670–3675.
(68) Kelemen, J. Dyes Pigm. 1981, 2, 73–91.
(69) For tautomer switches based on azo functional groups, see: (a)
Antonov, L.; Deneva, V.; Simeonov, S.; Kurteva, V.; Nedeltcheva,
D.; Wirz, J. Angew. Chem., Int. Ed. 2009, 48, 7875–7878. (b) Farrera,
J.-A.; Canal, I.; Hidalgo-Fernandez, P.; Perez-Garcia, M. L.; Huertas,
O.; Luque, F. J. Chem.sEur. J. 2008, 14, 2277–2285. (c) Matazo,
D. R. C.; Ando, R. A.; Borin, A. C.; Santos, P. S. J. Phys. Chem. A
2008, 112, 4437–4443. (d) Nihei, M.; Kurihara, M.; Mizutani, J.;
Nishihara, H. J. Am. Chem. Soc. 2003, 125, 2964–2973. (e) Kao, T.-
L.; Wang, C.-C.; Pan, Y.-T.; Shiao, Y.-J.; Yen, J.-Y.; Shu, C.-M.;
Lee, G.-H.; Peng, S.-M.; Chung, W.-S. J. Org. Chem. 2005, 70, 2912–
2920.
An increase in the torsional angles between the molecular
core and the peripheral aryl groups in this unfolded conformer,
9
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A R T I C L E S
Lee et al.
Scheme 8. Structural Folding and Unfolding Induced by
Solvent-Molecule Interactions
A brief exposure of the thin-film sample of 7 to diethylamine
vapor in the air, however, resulted in a dramatic color change
from pink to dark-orange, with a large hypsochromic shift of
the longer-wavelength transition from λmax ) 519 nm to λmax
) 478 nm (Figure 11a). Notably, this spectral change could be
reversed by evaporation of the amine after a brief application
of heat, and such switching cycles could be repeated >10 times
without noticeable deterioration of the performance of the
material (Figure 11c). Under similar conditions, however, the
thin-film sample of 8 underwent only a slight change in
absorption intensity with no shift of the absorption bands (Figure
11b), indicating that a direct interaction between the chromoge-
nic tris(hydrazone) core and the amine substrate is not the origin
of the large spectral shifts observed for 7.
Since Et2NH can function as either a hydrogen-bond donor
or acceptor, its interaction with the peripheral OH groups of 7
is likely to twist the peripheral aryl groups away from effective
conjugation with the tris(hydrazone) core in a manner similar
to the conformational switching and spectral blue shifts observed
in hydrogen-bonding solvents (Figure 10 and Scheme 8). We
note that the longer-wavelength spectral shift observed for solid
7 (∆λmax ) 41 nm; Figure 11a) is significantly larger than that
induced by hydrogen-bonding solvents such as MeOH or DMSO
(∆λmax ) 17-21 nm; Figure 10 and Table 4). This phenomenon
presumably reflects restricted motions of the putative amine
complexes of 7 in the solid state. As depicted in Scheme 8,
hydrogen-bonding solvent molecules would dynamically interact
with the terminal O-H groups to disrupt the structure-rigidifying
hydrogen-bonding network. As such, the UV-vis spectrum of
7 shown in Figure 10 reflects an ensemble of folded and
unfolded conformers that rapidly exchange in solution. In the
case of thin-film samples with slow exchange kinetics, however,
a significant portion of 7 is anticipated to retain the twisted (i.e.,
unfolded) conformation until the adsorbed amines are thermally
removed. Presumably, an effective conformational lock in the
solid state is responsible for larger spectral shifts through
binding-induced structural distortion.
in a manner similar to the situation in 9 (Figure 9), would
suppress the long-range electronic conjugation and elicit spectral
blue shifts. A conceptually related process was observed for
tris(N-salicylideneamine)-based molecular switches that respond
to polar solvents by changing the emission quantum yield18,20
or reversing the screw sense of the helical structure.22 The
validity of this working hypothesis was subsequently tested
using volatile amines as potential hydrogen-bonding agents
toward 7.
Colorimetric Detection of Hydrogen-Bonding Amines. The
solvent-dependent color change induced by structural folding
and unfolding of 7 (Figure 10 and Scheme 8) stimulated the
investigation of its response toward volatile amines that function
as potential hydrogen-bonding donors and/or acceptors. Thin
films of 7 (λmax ) 519 nm) and 8 (λmax ) 503 nm) were prepared
by drop-casting CHCl3 solution samples (1.0 mM) onto glass
substrates. As shown in Figure 11, the electronic absorption
spectra of these solid-state samples are essentially identical to
those measured for CHCl3 solution samples (Figure 10),
indicating that (i) the tautomeric and conformational structures
of the molecule are maintained even after aggregation and (ii)
no significant interchromophore electronic coupling exists in
the condensed phase.
In support of this mechanistic model, our colorimetric
detection scheme is generally applicable to a range of primary
and secondary amines with relatively low molecular weights
(Figure 11d). Intriguingly, triethylamine elicited little color
change despite the fact that it has a much higher vapor pressure
(57.07 mmHg at 25 °C) than n-hexylamine (8.99 mmHg at 25
°C) and a similar basicity (pKa ) 10.56 for Et3N; 10.75 for
n-C6H11NH2).70 This observation indicates that hydrogen-
bonding donor ability rather than intrinsic basicity is responsible
for the experimentally observed colorimetric response.
Selective recognition of primary, secondary, and tertiary
amines in solution has previously been demonstrated using
sensor arrays consisting of chemoresponsive dyes71,72 or
elaborate multitopic receptor molecules that exploit N-H· · ·O
hydrogen bonds and hydrophobic effects.73 Detection of Vapor
samples of amines having different substitution patterns,
however, still remains a significant challenge. Practical ap-
(70) CRC Handbook of Chemistry and Physics, 90th ed. (Internet version
2010); Lide, D. R., Ed.; CRC Press/Taylor and Francis: Boca Raton,
FL, 2010.
Figure 11. UV-vis spectra of thin films of (a) 7 and (b) 8 before (dotted
line) and after (solid line) exposure to a saturated vapor of diethylamine
under ambient conditions. In (a), photographic images are also shown in
the inset. (c) Color switching of the thin film of 7 monitored by the
absorbance change at 520 nm upon repeated cycles of adsorption of
diethyamine vapor and desorption by heating (5 s at 100 °C). (d) Response
profile of the thin film of 7 toward saturated amine vapors under ambient
conditions monitored by ∆A520nm. Thin-film samples were prepared by drop-
casting of 1.0 mM solution samples of 7 and 8 onto glass substrates.
(71) Zhang, C.; Suslick, K. S. J. Am. Chem. Soc. 2005, 127, 11548–11549.
(72) Montes-Navajas, P.; Baumes, L. A.; Corma, A.; Garcia, H. Tetrahedron
Lett. 2009, 50, 2301–2304.
(73) (a) Jung, J. H.; Lee, S. J.; Kim, J. S.; Lee, W. S.; Sakata, Y.; Kaneda,
T. Org. Lett. 2006, 8, 3009–3012. (b) Jung, J. H.; Lee, H. Y.; Jung,
S. H.; Lee, S. J.; Sakata, Y.; Kaneda, T. Tetrahedron 2008, 64, 6705–
6710.
9
12142 J. AM. CHEM. SOC. VOL. 132, NO. 34, 2010

Torsionally Responsive C3-Symmetric Azo Dyes
A R T I C L E S
2H), 4.53 (s, 2H), 2.16 (s, 2H), 1.62 (s, 12H), 1.22 (s, 9H). 13C
NMR (100 MHz, CDCl3, 298 K): δ 146.2, 140.3, 129.7, 106.8,
99.3, 78.9, 65.9, 33.9, 31.8, 31.4. FT-IR (thin film on NaCl, cm-1):
3374, 2967, 2867, 2216, 1609, 1583, 1461, 1411, 1394, 1362, 1327,
1306, 1232, 1192, 1163, 972, 941, 909, 883, 854, 734, 641. HR
ESI-MS: calcd for C20H27NO2Na [M + Na]+, 336.1939; found,
336.1926.
proaches often employ perturbations of delocalized electronic
structures associated with π-π-stacked organic molecules74 or
conjugated polymers,75 which give rise to changes in their
optoelectronic properties. Statistical analysis on colorimetric
sensor arrays has also complemented such efforts.76 The torsion-
induced changes in electronic properties described in the current
work offer an alternative signal transduction mechanism that
exploits predictable and controllable molecular motions.
(2E,4E,6E)-2,4,6-Tris(2-(4-tert-butyl-2,6-bis(3-hydroxy-3-meth-
ylbut-1-yn-1-yl)phenyl)hydrazono)cyclohexane-1,3,5-trione (7). A
20 mL vial was charged with 6 (0.258 g, 0.823 mmol), MeOH (5
mL), 2 M aqueous HCl (3 mL), and a magnetic stir bar. The reaction
mixture was cooled to 0 °C using an ice bath and stirred. A
precooled (0 °C) aqueous solution (3 mL) of NaNO2 (81.1 mg,
1.17 mmol) was added using a pipet over a period of 10 min, and
the reaction mixture was stirred for additional 10 min at 0 °C. A
250 mL round-bottom flask was charged with phloroglucinol
dihydrate (31.3 mg, 0.193 mmol), MeOH (20 mL), 2 M aqueous
NaOH (3.10 mL), and a magnetic stir bar and cooled to 0 °C. A
pipet was used to add the diazonium reaction mixture containing 6
over a period of 20 min. The resulting mixture was stirred for
additional 0.5 h at 0 °C and then neutralized by addition of 2 M
aqueous HCl. The mixture was diluted with water (100 mL), and
the organic fraction was extracted into EtOAc (100 mL × 2) and
washed with water (100 mL). Volatile fractions were removed under
reduced pressure, and the residual material was purified by flash
column chromatography on SiO2 [hexanes/EtOAc ) 4:1 (v/v)] to
furnish 7 as a dark-red solid (0.171 g, 0.155 mmol, 81%). A single
crystal of 7 suitable for X-ray crystallography was obtained by slow
cooling of a boiling saturated CH3CN solution of this material. 1H
NMR (400 MHz, CDCl3, 298 K): δ 16.4 (s, 3H), 7.48 (s, 6H),
5.72 (s, 3H), 1.59 (s, 36H), 1.33 (s, 27H). 13C NMR (100 MHz,
CDCl3, 298 K): δ 178.2, 150.4, 139.5, 131.5, 129.2, 114.7, 101.7,
77.8, 65.2, 34.8, 31.3, 31.1. FT-IR (thin film on NaCl, cm-1): 3423,
1968, 2931, 2869, 1600, 1585, 1474, 1440, 1411, 1394, 1364, 1308,
1239, 1218, 1186, 1071, 1036, 1020, 953, 885, 862. HR ESI-MS:
calcd for C66H78N6O9Na [M + Na]+, 1121.5728; found, 1121.5747.
(2E,4E,6E)-2,4,6-Tris(2-(4-tert-butylphenyl)hydrazono)cyclohex-
ane-1,3,5-trione (8). This compound was prepared using 4-tert-
butylaniline (0.505 g, 3.38 mmol) and phloroglucinol dihydrate
(0.117 g, 0.721 mmol) in a manner similar to that described for 7.
The product was isolated as a bright-red solid (0.151 g, 0.247 mmol,
34%) after flash chromatography on SiO2 [hexanes/EtOAc ) 10:1
to 4:1 (v/v)]. 1H NMR (400 MHz, CDCl3, 298 K): δ 16.4 (s, 3H),
7.59 (d, J ) 11.6 Hz, 6H), 7.48 (d, J ) 11.2 Hz, 6H), 1.35 (s,
27H). 13C NMR (100 MHz, CDCl3, 298 K): δ 178.7, 151.2, 139.0,
128.7, 126.8, 117.5, 34.9, 31.4. FT-IR (thin film on NaCl, cm-1):
2963, 2926, 2869, 1601, 1471, 1436, 1409, 1364, 1308, 1241, 1172,
1098, 1054, 843. HR ESI-MS: calcd for C36H43N6O3 [M + H]+,
607.3397; found, 607.3372.
Summary and Outlook
New C3-symmetric conjugated molecules based on a tris(hy-
drazone) platform were prepared by simple triple azo coupling
reactions. A combination of solution 1H/13C NMR and UV-vis
spectroscopy, single-crystal X-ray crystallography, and DFT
computational studies provided compelling evidence for the
existence of a keto-hydrazone rather than an enol-azo tauto-
meric core, which gives rise to characteristic longer-wavelength
UV-vis absorption bands at λmax ) 445-523 nm. The branched
[n,π] conjugation responsible for these intense visible transitions
can be modulated through twisting of the C-N bonds that
connect the molecular core to the peripheral aryl groups.
Notably, this molecular switch could be driven by the assembly
and disassembly of a hydrogen-bonding network through
interaction with exogenous agents. A signal transduction mech-
anism that exploits such binding-induced conformational transi-
tions was implemented for thin-film samples that undergo
reversible color switching upon exposure to selected primary
and secondary amine vapors. Efforts to expand the scope of
this chemistry by structurally engineering these proof-of-
principle prototypes to target an expanded set of analytes are
underway.
Experimental Section
General Considerations. All of the reagents were obtained from
commercial suppliers and used as received, unless otherwise noted.
The compound 4-tert-butyl-2,6-diiodoaniline was prepared accord-
ing to a literature procedure.77 All air-sensitive manipulations were
carried out under a nitrogen atmosphere using standard Schlenk
line techniques.
Physical Measurements. 1H and 13C NMR spectra were recorded
on a 300 MHz Varian Gemini 2000 or 400 MHz Varian Inova
NMR spectrometer. Chemical shifts were reported versus tetram-
ethylsilane and referenced to the residual solvent peaks. High-
resolution electrospray ionization mass spectrometry (HR ESI-MS)
was performed on a Thermo Electron Corporation MAT 95 XP-
Trap mass spectrometer. FT-IR spectra were recorded on a Nicolet
Avatar 360 FT-IR spectrometer with EZ OMNIC ESP software.
UV-vis spectra were recorded on a Varian Cary 5000 UV-vis-NIR
spectrophotometer.
(2E,4E,6E)-2,4,6-Tris(2-(2,6-diisopropylphenyl)hydrazono)cy-
clohexane-1,3,5-trione (9). This compound was prepared using 2,6-
diisopropylaniline (0.304 g, 1.71 mmol) and phloroglucinol dihy-
drate (57.1 mg, 0.352 mmol) in a manner similar to that described
for 7. The product was isolated as a bright-red solid (0.201 g, 0.290
mmol, 82%) after flash chromatography on SiO2 [hexanes/dichlo-
2,6-Bis(3-methyl-3-hydroxyl-1-butynyl)-4-tert-butylaniline (6). A
round-bottom flask was charged with 4-tert-butyl-2,6-diiodoaniline
(1.83 g, 4.56 mmol), 2-methylbut-3-yn-2-ol (860 mg, 10.2 mmol),
iPr2NH (20 mL), PdCl2(PPh3)2 (81.2 mg, 0.115 mmol), CuI (43.1
mg, 0.225 mmol), and THF (40 mL). The mixture was purged with
N2, stirred for 24 h at room temperature (rt), and concentrated under
reduced pressure. Flash column chromatography on SiO2 [hexanes/
EtOAc ) 2:1 to 1:1 (v/v)] furnished 6 as a yellow solid (1.32 g,
4.21 mmol, 92%). 1H NMR (400 MHz, CDCl3, 298 K): δ 7.24 (s,
1
romethane ) 1:1 to 1:2 (v/v)]. H NMR (400 MHz, CDCl3, 298
K): δ 16.0 (s, 3H), 7.27 (t, J ) 6.8 Hz, 3H), 7.22 (d, J ) 12.8 Hz,
6H), 3.24 (septet, J ) 6.8 Hz, 6H), 1.25 (d, J ) 6.8 Hz, 36H). 13
C
NMR (100 MHz, CDCl3, 298 K): δ 178.7,143.4, 136.7, 129.2,
128.8, 123.9, 28.4, 23.7. FT-IR (thin film on NaCl, cm-1): 2959,
2903, 2867, 1601, 1578, 1477, 1421, 1405, 1363, 1320, 1287, 1230,
1171, 1118, 1052, 833. HR ESI-MS: calcd for C42H55N6O3 [M +
H]+, 691.4336; found, 691.4318.
(74) (a) Che, Y.; Yang, X.; Loser, S.; Zang, L. Nano Lett. 2008, 8, 2219–
2223. (b) Che, Y.; Zang, L. Chem. Commun. 2009, 5106–5108. (c)
Che, Y.; Yang, X.; Zhang, Z.; Zuo, J.; Moore, J. S.; Zang, L. Chem.
Commun. 2010, 46, 4127–4129.
X-ray Crystallographic Studies. The data collection was carried
out using synchrotron radiation (λ ) 0.41328 Å, diamond 111
monochromator) from the 15-ID ChemMatCARS beamline at the
Advanced Photon Source, Argonne National Laboratory, with a
frame time of 1 s and a detector distance of 6.0 cm. A yellow needle
(approximate dimensions 0.10 mm × 0.03 mm × 0.03 mm) was
(75) Liu, W.; Pink, M.; Lee, D. J. Am. Chem. Soc. 2009, 131, 8703–8707.
(76) Rakow, N. A.; Sen, A.; Janzen, M. C.; Ponder, J. B.; Suslick, K. S.
Angew. Chem., Int. Ed. 2005, 44, 4528–4532.
(77) Iskra, J.; Stavber, S.; Zupan, M. Synthesis 2004, 1869–1873.
9
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A R T I C L E S
Lee et al.
placed onto the tip of a 0.05 mm diameter glass fiber and mounted
on a platform diffractometer equipped with an APEX II detector
at 120(2) K. Two major sections of frames were collected with a
step size of 0.5° in φ and a detector position of -5.0° in 2θ. Data
to a resolution of 0.70 Å were considered in the reduction. Final
cell constants were calculated from the xyz centroids of 2509 strong
reflections from the actual data collection after integration
(SAINT).78 The intensity data were corrected for absorption
solute surface. Thermodynamic properties were calculated following
standard protocol:
Gsol ) Ggas + Gsolv
Ggas ) Hgas - TSgas
Hgas ) ESCF + ZPE
(2)
(3)
(4)
where Ggas is the free energy in the gas phase, Gsolv is the free
energy of solvation computed using the continuum solvation model,
Hgas is the enthalpy in the gas phase, T is the temperature ()298.15
K), Sgas is the entropy in the gas phase, ESCF is the self-consistent
field energy (i.e., the “raw” electronic energy computed from the
SCF procedure), and ZPE is the zero-point energy.
(SADABS).79 The space group P1 was determined on the basis of
j
intensity statistics and systematic absences. The structure was solved
and refined using SHELXTL.80 A direct-methods solution was
calculated and provided most of the atomic positions from the E
map. Full-matrix least-squares/difference Fourier cycles were refined
with anisotropic displacement parameters. The hydrogen atoms were
placed in ideal positions and refined as riding atoms with relative
isotropic displacement parameters. The final full-matrix least-
squares refinement converged to R1 ) 0.1084, wR2 ) 0.2192 (F2,
all data). The remaining electron density was minuscule and located
near the tert-butyl moieties.
DFT Calculations. All of the calculations were performed using
DFT. Geometry optimizations were performed using the Jaguar 6.0
suite of ab initio quantum chemistry programs81 at the B3LYP/6-
31G** level of theory.82,83 Frequencies were calculated at the same
level to gain the zero-point energy and entropy. All of the stationary
points were confirmed to be minima by checking the harmonic
frequencies. The energies of the optimized structures were reevalu-
ated by additional single-point calculations on each optimized
geometry using Dunning’s correlation-consistent triple-ꢀ cc-pVTZ(-
f) basis set.84 Solvation energies were calculated using a self-
consistent reaction field (SCRF) method based on accurate numer-
ical solutions of the Poisson-Boltzmann equation.85 Empirical
parameters such as dielectric constant (ε ) 4.806, CHCl3) and
atomic radii (H, 1.140 Å; C, 1.900 Å) were used to construct the
The gas-phase 13C NMR shielding constants σ were calculated
from the coupled perturbed Hartree-Fock (CPHF)86 wave function
using Jaguar at the B3LYP/6-31G** level. The value of σref for
the reference molecule tetramethylsilane (TMS) was calculated
using the same basis set and the same method. The chemical shift
δ, which is typically what is measured in an NMR experiment,
was then calculated as
δ ) σref - σ
(5)
Acknowledgment. This work was supported by the National
Science Foundation (CHE 0547251 and CHE 0645381) and the
U.S. Army Research Office (W911NF-07-1-0533). Use of the
Advanced Photon Source was supported by the U.S. Department
of Energy under Contract DE-AC02-06CH11357. ChemMatCARS
Sector 15 is principally supported by the National Science Founda-
tion and Department of Energy under Grant CHE-0535644. We
thank the Sloan Foundation (Alfred P. Sloan Research Fellowship
to D.L.) and the Research Corporation (Cottrell Scholarship to M.-
H.B.) for partial support of this work. We thank Dr. Nikolay
Tsvetkov for helpful comments.
(78) SAINT; Bruker Analytical X-Ray Systems: Madison, WI, 2009.
(79) Blessing, R. H. Acta Crystallogr. 1995, A51, 33–38.
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(81) Jaguar, version 7.0; Schrodinger, LLC: New York, 2007.
(82) Becke, A. D. J. Phys. Chem. 1993, 98, 5648–5652.
(83) Lee, C. T.; Yang, W. T.; Parr, R. G. Phys. ReV. B 1988, 37, 785–789.
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Ringnalda, M. N.; Pollard, W. T.; Dunietz, B. D.; Cao, Y. X. J. Phys.
Chem. A 1999, 103, 1913–1928. (c) Edinger, S. R.; Cortis, C.; Shenkin,
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Supporting Information Available: Additional spectroscopic
and computational data and crystallographic data (CIF). This
material is available free of charge via the Internet at http://
pubs.acs.org.
JA105121Z
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12144 J. AM. CHEM. SOC. VOL. 132, NO. 34, 2010