Photoinduced conformational switch of enantiopure azobenzenes controlled by a sulfoxide

Article abstract of DOI:10.1021/ja070163o

Two series of enantiopure azobenzenes with a p-tolylsulfoxide at the ortho or meta position with respect to the azo group, have been regioselectively synthesized. Both can act as enantiopure molecular switches showing different structural features owing t

Full text of DOI:10.1021/ja070163o

Published on Web 05/12/2007
Photoinduced Conformational Switch of Enantiopure
Azobenzenes Controlled by a Sulfoxide
M. Carmen Carren˜o,*,† Isabel Garc´ıa,† Irene Nu´n˜ez,† Est´ıbaliz Merino,†
Mar´ıa Ribagorda,*,† Silvia Pieraccini,‡ and Gian Piero Spada‡
Contribution from the Departamento de Qu´ımica Orga´nica (C-I), UniVersidad Auto´noma de
Madrid, Cantoblanco, 28049-Madrid, Spain, and Alma Mater Studiorum-UniVersita` di Bologna,
Dipartamento di Chimica Organica “A. Mangini”, Via San Giacomo 11, 40126 Bologna, Italy
Received January 9, 2007; E-mail: carmen.carrenno@uam.es; maria.ribagorda@uam.es
Abstract: Two series of enantiopure azobenzenes with a p-tolylsulfoxide at the ortho or meta position with
respect to the azo group, have been regioselectively synthesized. Both can act as enantiopure molecular
switches showing different structural features owing to the presence of the stereogenic sulfur. The
photoisomerization process, studied by UV-vis, circular dichroism (CD), NMR, and chiral HPLC evidenced
a double role of the sulfoxide. A transfer of chirality from the sulfoxide to the azo system was observed by
CD in both cis and trans-isomers of the meta sulfinyl derivatives 3, whereas this perturbation was evident
for the ortho sulfinyl series 7 only in the cis isomer. The NMR study evidenced that the s-cis rigid conformation
of the bisaromatic sulfoxide was fixing a different orientation of the overall system in each series both in
the trans and cis isomers, by forcing a final U-shaped structure in cis-3 and an S-shaped structure in cis-7.
Very different values of specific optical rotations were measured in both trans and cis isomers, also reflecting
the existence of distinct chiral entities in the photostationary states. The easy and reversible changes
occurring between different conformational states could find applications in the photocontrol of several
molecular switches.
Introduction
upon irradiation, the motion of a molecule containing an
azobenzene is able to regulate the movement of a complemen-
Among the strategies developed to control molecular motion,
photoinduced transformations are of increasing importance
because of the reversibility and selectivity that can be achieved
by using light of a defined wavelength.1 Photochemical E/Z
isomerization of azobenzenes has been shown to be an efficient
tool to modulate the relative movement of different moieties
integrated into a molecule. Numerous photoswitchable devices
based on the NdN photoisomerization, such as crown ethers,2
molecular shuttles,3 and nanotubes4 have been reported. When
included in biological systems such as polypeptides1e,5 or
enzymes6 the photoresponse may modify the activity. The
photoisomerization of an azo group can produce a change in
folding and/or conformational preference of a polymer7,8 or a
dendrimer9 evidencing that local fluctuation can be correlated
with macrostructural movements. A recent study has shown that,
tary substrate.10 The interconnectivity between conformation and
reactivity is motivating the design of new devices both from
biological and chemical systems where the local conformation
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W.; Moroder, L.; Renner, C. Chem.sEur. J. 2006, 12, 1114-1120. (b)
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† Universidad Auto´noma de Madrid.
‡ Universita` di Bologna.
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J. Chem. 2006, 59, 155-229 (monographic issue). (c) Gillespie, D. C.;
Kim, G.; Kandler, K. In Dynamic Studies in Biology, 1st ed.; Goeldner,
M., Givens, R., Eds.; Wiley-VCH: Weinheim, Germany, 2005; pp 232-
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Switches, Feringa, B. L., Ed.; Wiley-VCH: Weinheim, Germany, 2001;
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10.1021/ja070163o CCC: $37.00 © 2007 American Chemical Society
J. AM. CHEM. SOC. 2007, 129, 7089-7100
7089

A R T I C L E S
Carren˜o et al.
Scheme 1. Synthesis of 4-Methoxy-3-substituted Aryl
Azobenzenes 3 from Subtituted p-Benzoquinone Bisketals 1 and
Arylhydrazines 2
of a chromophore can be modified by irradiation thus opening
the way to new applications of azobenzenes.11
Trans azobenzenes usually display a nearly planar structure,
which after isomerization adopts a bent geometry as a conse-
quence of the more stable edge to face orientation of both aryl
groups present in the cis azo isomer.5g,12-14 Unsubstituted or
symmetrically substituted azobenzenes exist as single conform-
ers for each E and Z isomers. The presence of ortho or meta
substituents in the benzene rings introduces a structural distortion
where different conformations can coexist. These features are
particularly relevant in the photochromic properties of azoben-
zenes. When the azobenzene is included on chiral macrostruc-
tures, photomodulation of chiroptical properties has been
exploited for biological recognition,15 photoregulation func-
tions16 or photoresponsive polymers.17d Chiral stereogenic
carbons are in these cases responsible for the changes observed
with chiroptical techniques, such as circular dichroism (CD) or
optical rotation. The few studies reported on simple analogues
with central chirality as dopants for liquid crystals (LC), had
shown that the helical twisting power (â),18 a parameter
measuring the influence of a dopant to torque a nematic phase
in its lower concentration limit, is generally medium-to-low.21b,19
Photoinduced chirality was observed by irradiating an achiral
azobenzene containing polymer with circularly polarized light.20
Axially chiral azocompounds, derived from binaphthyls, have
been reported to induce remarkable variation in optical switching
of LC.21
had only been involved in the nematic doping technique to
determine the absolute configuration of some alkyl aryl sul-
foxides.23
In 2004, we reported a new synthesis of azobenzenes,24 based
on the reaction of p-benzoquinone bisketals 1 with arylhydra-
zines 2 (Scheme 1). The method was shown to be general to
other p-benzoquinone ketals. Moreover, the soft conditions
required, allowed us to introduce an enantiopure sulfoxide on
the aromatic moiety without loss of configurational integrity.
Taking into account the easy incorporation of the enantiopure
sulfoxide into the azobenzene, we decided to study the behavior
of the resulting systems in the photoisomerization process. A
preliminary investigation of the chiroptical properties of [S(S)]-
3-p-tolylsulfinyl azobenzenes 325 (Scheme 1, R ) SOp-Tol),
revealed that the pendant sulfoxide had a significant influence
on the overall geometry and chirality of the azo moiety. With
the aim of validating the role of the sulfoxide to induce a chiral
perturbation on the azocompound, we embarked on the study
of a series of enantiopure azobenzenes where the sulfoxide was
situated at different positions. In this paper we report the
regiocontrolled synthesis of a novel family of enantiopure
azobenzenes where the ortho or meta position of the sulfoxide
with respect to the NdN group, is able to produce a chiral
perturbation on the E or Z isomers. A study of the photoisomer-
ization by UV, CD, and NMR has revealed that, upon irradia-
tion, the fixed conformation of the E-isomers undergoes a
conformational change which is fully controlled by the sulfoxide.
The sulfinyl azobenzenes have been tested as chiral dopants
for liquid crystals by measuring the â values induced by the
photoisomerization in a crystalline environment. Our previous
work on the synthesis and preliminary study of the photochromic
properties of 3-sulfinyl substituted azobenzenes25 is also dis-
cussed in full detail, including results not described in our earlier
communication.
In spite of the extensive use of sulfoxides in asymmetric
synthesis,22 they have been scarcely incorporated into chiral
molecular switches. To the best of our knowledge, this motif
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261. (b) Renner, C.; Moroder, L. ChemBioChem 2006, 7, 868-778.
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28, 8368-8374.
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Results and Discussion
Both 2- and 3-(p-tolylsulfinyl) azobenzenes 3 and 7 were
prepared from a common enantiopure starting material, [S(S)]-
1,4-dimethoxy-2-(p-tolylsulfinyl)benzene 4,26 readily available
from 2-bromo-1,4-dimethoxy benzene after bromo-lithium
exchange followed by reaction with menthyl [S(S)]-p-toluene
sulfinate27,28 (Scheme 2). The anodic oxidation of 4 (single cell,
Pt/Cu, 1 A, 2 V, MeOH, KOH, 0 °C)29 led to 2-(p-tolylsulfinyl)-
(18) The â value is expressed as â ) (pc)-1, where p (µm) is the cholesteric
pitch length and c (mol/mol) is the molar fraction of the enantiopure chiral
dopant. The sign is taken positive for a right-handed cholesteric and negative
for a left-handed one. For example see: Gottarelli, G.; Spada, G. P. In
MaterialssChirality; Green, M. M., Nolte, R. J. M., Meijer, E. W., Eds.;
Topics in Stereochemistry Series, Vol 24; Wiley: New York, 2003; Chapter
7, pp 425-455.
(19) (a) Kurihara, S.; Yoshioka, T.; Ogata, T.; Zahangir, A. M.; Nanaka, T.
Liq. Cryst. 2003, 10, 1219-1223. (b) Ruslim, C.; Ichimura, K. J. Mater.
Chem. 2002, 12, 3377-3379. (c) Ruslim, C.; Ichimura, K. AdV. Mater.
2001, 13, 37-39. (d) Heppke, G.; Marschall, H.; Nurnberg, P.; Oestreicher,
F.; Scherowsky, G. Chem. Ber. 1981, 114, 2501-2518.
(20) (a) Kim, M.-J.; Shin, B.-G.; Kim, J.-J.; Kim, D.-Y. J. Am. Chem. Soc.
2002, 124, 3504-3505. (b) Wu, Y.; Natanshon, A.; Rochon, P. Macro-
molecules 2004, 37, 6801-6805.
(21) (a) Van Delden, R. A.; Mecca, T.; Rosini, C.; Feringa, B. L. Chem.sEur.
J. 2004, 10, 61-70. (b) Pieraccini, S.; Gottarelli, G.; Labruto, R.; Masiero,
S.; Pandoli, O.; Spada, G. P. Chem.sEur. J. 2004, 10, 5632-5639. (c)
Jaycox, G. D. J. Polym. Sci., Part A: Polym. Chem. 2004, 42, 566-577.
(d) Pieraccini, S.; Masiero, S.; Spada, G. P.; Gottarelli, G. Chem. Commun.
2003, 598-599. (e) Lustig, S. R.; Everlof, G. J.; Jaycox, G. D. Macro-
molecules 2001, 34, 2364-2372.
(22) (a) Ferna´ndez, I.; Khiar, N. Chem. ReV, 2003, 103, 3651-3705. (b) Carren˜o,
M. C. Chem. ReV. 1995, 95, 1717-1760. (c) Solladie´, G. Synthesis, 1981,
185-196.
(23) Pieraccini, S.; Donnoli, M. I.; Ferrarini, A.; Gottarelli, G.; Licini, G.; Rosini,
C.; Superchi, S.; Spada, G. P. J. Org. Chem. 2003, 68, 519-526.
(24) Carren˜o, M. C.; Ferna´ndez Mudarra, G.; Merino, E.; Ribagorda, M. J. Org.
Chem. 2004, 69, 3413-3416.
(25) Carren˜o, M. C.; Garc´ıa, I.; Ribagorda, M.; Merino, E.; Pieraccini, S.; Spada,
G. P. Org. Lett. 2005, 7, 2869-2872.
(26) (a) Carren˜o, M. C.; Garc´ıa Ruano, J. L.; Urbano, A. Synthesis 1992, 651-
653. (b) Carren˜o, M. C.; Garcia Ruano, J. L.; Urbano, A. Tetrahedron Lett.
1989, 30, 4003-4006.
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R. I. J. Am. Chem. Soc. 1964, 86, 5637-5646.
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1991, 47, 605-614.
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Photoinduced Conformational Switch of Azobenzenes
A R T I C L E S
Scheme 2. Synthesis of [S(S)]-4-Methoxy-3-p-
tolylsulfinyl-azobenzenes 3a-e
Scheme 3. Synthesis of [S(S)]-5-Bromo-4-methoxy-2-p-
tolylsulfinyl Azobenzenes 7a-ea
p-benzoquinone tetramethylbisketal 1 in 89% yield. Reaction
of 1 with differently substituted arylhydrazines 2a-e, in the
presence of a catalytic amount (4-8% mol) of Ce(NH4)2(NO3)6
(CAN), yielded azobenzenes 3a-e. This reaction led to the
exclusive formation of the regioisomers situating the sulfoxide
at the meta position (C-3) of the aromatic ring with respect to
the azo group, in good to excellent yields (60-94%). The
regioselectivity is due to the preferred attack of the arylhydra-
zines 2 to the less hindered dimethyl ketal group of 1, placed
far from the sulfoxide.
On the basis of this methodology, we planned the access to
regioisomeric azobenzenes 7, bearing the sulfoxide closer to
the azo moiety. Taking into account the steric control of these
reactions, we reasoned to direct the attack of the hydrazine to
the ketal group situated close to the sulfoxide by hindering the
reaction at the ketal situated far from it. With this aim, we
introduced an extra bulky substituent at C-4 of the 1-p-
tolylsulfinyl-3,3,6,6-tetramethoxy-1,4-cyclohexadiene 1, which
could direct the hydrazine attack to C-6. Considering these steric
requirements, we thought of a C-4 bromo derivative. The
bromine could be introduced in the precursor 4 by reaction with
NBS in MeCN.30 To our delight, aryl bromination of 4 occurred
in a highly regioselective manner giving exclusively the
5-bromo-2-p-tolylsulfinyl derivative 5, which precipitated from
the reaction mixture and was isolated pure in 62% yield (Scheme
3). Anodic oxidation of 5 (1 A, 2 V, MeOH, KOH, 0 °C) led
to a 60:40 mixture of the desired [S(S)]-4-bromo-1-p-tolylsulfi-
nyl-3,3,6,6-tetramethoxy-1,4-cyclohexadiene 6 and the debro-
minated product 1, respectively. Although it is known that in
the anodic oxidation of bromo aromatic compounds a reductive
debromination can occur by cathodic cleavage,31 Swenton et
al. had reported that the C-Br bond rupture can be minimized
by lowering the reaction temperature to -3 °C32 or performing
a Reaction of 6 with o-CF3C6H4NHNH2 was performed in refluxing
MeCN without CAN.
the anodic oxidation in a divided cell.33 In our case, the decrease
of the temperature was not effective enough and it was necessary
to optimize the electrochemical conditions. Fortunately, the
anodic oxidation of 5 could be successfully conducted in a single
cell apparatus using a cylindrical 5 cm diameter × 5 cm 45
mesh Pt anode and a carbon electrode situated inside as a
cathode, in a methanol solution with KOH as electrolyte and
lowering the current efficiency to 0.1 A and the reaction
temperature to -5 °C. Under these conditions a 96:4 mixture
of 6 and 1 resulted, from which compound 6 could be separated
as pure by chromatography in a 90% yield (Scheme 3).
Next, we treated bisketal 6 with arylhydrazines 2a-e. In all
cases but one, the formation of azobenzenes was successfully
achieved by treating a MeCN solution of 6 and 2 with CAN
(30 mol %) at room temperature. The reaction of 6 with ortho-
CF3 substituted phenylhydrazine 2d gave better yields in
refluxing MeCN and in the absence of CAN. The 5-bromo-4-
methoxy-2-p-tolylsulfinyl azobenzene derivatives 7 were ob-
tained as single regioisomers in good yields. A detailed
comparison of the behavior of both quinone bisketals 1 and 6
revealed that the formation of azobenzenes 7 required higher
amounts of CAN and longer reaction times than the 3-sulfinyl
substituted analogues 3. The structure of the azocompounds 3
and 7 was inferred from their NMR parameters, including
NOESY experiments (discussed later) to establish the substitu-
tion at the sulfoxide-bearing ring. Moreover, the structures of
3c and 7b were unequivocally assigned by X-ray crystal
structure analysis (Figure 1).34
(30) Carren˜o, M. C.; Garc´ıa Ruano, J. L.; Sanz, G.; Toledo, M. A.; Urbano, A.
J. Org. Chem. 1995, 60, 5328-5331.
(31) (a) Casanova, J.; Eberson, L. In The Chemistry of the Carbon Halogen
Bond; Patai, S., Ed.; Wiley: London, 1973. (b) Belloncle, C.; Cauliez, P.;
Simonet, J. J. Electroanal. Chem. 1998, 444, 101-112.
(32) See footnote 12 and the following: Manning, M. J.; Raynolds, P. W.;
Swenton, J. S. J. Am. Chem. Soc. 1976, 98, 5008-5009.
(33) Henton, D. R.; McCreery, R. A.; Swenton, J. S. J. Org. Chem. 1980, 45,
369-378.
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A R T I C L E S
Carren˜o et al.
shown in Figures 2 and 3 (b, d, f, and h), respectively. Upon
irradiation with a 150 W Xe-lamp, the absorptions of the
sulfoxide were not altered.
The changes observed in the absorption bands corresponding
to the azo group evidenced the E f Z isomerization. A decrease
of the intensity of this band was observed in all cases. These
spectral changes are a common feature of the trans to cis
isomerization of azobenzenes.12 The Z photostationary states,
PSScis, were reached in 5 min for azocompounds 3 and in 19-
40 min for 7. The different rate of photoisomerization, which
is very similar in different solvents within a series, is noteworthy.
A slower photoisomerization of ortho-ortho′ disubstituted
azobenzenes bearing bulky substituents had been previously
reported.35 On this basis, we assume that the slower process
observed in 7 must be due to the ortho sulfoxide. Thermal
relaxation was much slower than the photoinduced isomeriza-
tion. For example, the initial states of trans-3a and trans-7d
were regained after keeping the samples in the dark for 7 and
9 days at 22-25 °C, respectively.
The absorption spectra of the dinitro-substituted derivatives
3e and 7e remained unchanged upon irradiation at different
wavelengths and in different solvents (hexane, MeCN, EtOH,
or CHCl3). A very fast switching between trans and cis isomers
at room temperature can be disregarded since it was already
known the reduced photoreactivity of nitro-substituted azoben-
zenes that they cannot be used as photochemical switches.39
The CD spectra of the trans-3a-d showed two main bands:
one at λ < 250 nm,40 corresponding to the [S(S)]-sulfoxide,
and a second positive Cotton effect at ca. 350 nm, which was
assigned to the azo group, reflecting some transfer of chirality
from the sulfoxide to the azo system.41 Upon irradiation of a
THF solution of 3a-d (λ ) 365 nm), the CD band at 250 nm
remained unaltered confirming the configurational photostability
of the enantiopure sulfoxide. This configurational integrity was
also verified by HPLC analysis of 3c before and after irradiation,
where no racemization was observed.
The π f π* transition bands at 350 nm, reduced their
intensity upon irradiation, while a new positive CD signal at
ca. 430 nm (n f π* transition) appeared (Figure 2a, c, e, and
g, pink line). These spectral changes suggested that the E/Z
isomerization of the azo moiety has a notable influence on the
overall geometry and chirality of 3a-d. The appearance of the
new band at 430 nm in the cis isomers suggests that the
sulfoxide is inducing a different chiral perturbation in the E
and Z isomers. Reverse CD spectral changes occurred after
irradiation of 3a-d at λ ) 436 nm for 5 min (Figure 2a, c, e,
and g, green line). The sequential irradiation was repeated five
times without alteration of the CD and UV-vis spectra for the
PSSs, confirming the configurational integrity of these systems.
Enantiopure trans azobenzenes 7a-d showed the positive CD
signal at λ < 250 nm of the sulfur stereogenic center (Figure
3a, c, e, and g, blue line). To our surprise, the dichroic signal
around 350 nm for the azo group did not appear, suggesting
Figure 1. Molecular diagrams derived from X-ray crystal structures of (a)
trans-3c and (b) trans-7b.
A comparative analysis of the X-ray crystal structures of
trans-3c and trans-7b revealed that, while trans-7b adopted the
general coplanar rodlike disposition of azobenzenes (Figure 1b),
trans-3c displayed an uncommon torsion angle of 45.74° (red
angle) for the perfluorotolyl NdN moiety and 18.54° (black
angle) for the sulfinylaryl NdN fragment (Figure 1a). Such a
deviation of planarity would have been more predictable for
the ortho-substituted sulfinyl azobenzene, since a similar aryl
rotation in ortho,ortho-disubstituted azobenzenes has been
reported,35 which is enhanced by increasing the volume of the
ortho substituent. In our case, this exceptional twisted disposition
must be forced by the remote aromatic ring of the sulfoxide
situated at the meta position in 3c, which is strongly influencing
the overall geometry. Moreover, the conformer around the C-S
bond of the sulfoxide in both 3b and 7b is the one situating the
sulfinyl oxygen in a 1,3-parallel disposition with respect to the
vicinal hydrogen (s-cis conformation). Although this could be
influenced by the packing in the solid state, this is unlikely since
the s-cis rotamer has been found to be the most stable in both
aromatic and vinyl sulfoxides.36
Photoisomerization UV and CD Studies. To evaluate the
changes associated with the photoisomerization of 3a-e and
7a-e containing the enantiopure sulfoxide, we irradiated the
azobenzenes and monitored the process by UV-vis and CD in
THF (3a-e) and CHCl3 (7a-e).37 The initial UV-vis spectra
of both regioisomers were very similar. Two main absorption
bands appeared in the trans isomer, one in the region of λ <
250 nm where the sulfoxide group absorbs, and a band at
350-400 nm (π f π* transition) owing to the aromatic azo-
chromophore.21c,38 The UV-vis spectra of 3a-d and 7a-d are
(38) Suzuki, H. Electronic Absorption Spectra and Geometry of Organic
Molecules, Academic Press: New York, 1967; p 503.
(39) For a discussion on the effect on meta/para substitution on the photoreac-
tivity of an azobenzene, see Cisnetti, F.; Ballardini, R.; Credi, A.; Gandolfi,
M. T.; Masiero, S.; Negri, F.; Pieraccini, S.; Spada, G. P. Chem.sEur. J.
2004, 10, 2011-2021.
(34) (a) For details see Supporting Information. (b) Space group for trans-3c is
P2(1)2(1)2(1) and for trans-7b is P1h.
(35) Rau, H.; Yu-Quan, S.; J. Photochem. Photobiol., A: Chem. 1988, 42 1631-
1632.
(40) The lower Cotton effect observed for the sulfoxide band in 3b is not easy
to explain.
(36) Kahn, S. D.; Hehre, W. J. J. Am. Chem. Soc. 1986, 108, 7399-7400.
(37) The solvent was chosen according to the major changes observed in the
CD spectra before and after irradiation.
(41) The Cotton effect of such an intrinsically achiral electronic transition may
be due to its coupling with the electronic transition of the chiral sulfoxide.
9
7092 J. AM. CHEM. SOC. VOL. 129, NO. 22, 2007

Photoinduced Conformational Switch of Azobenzenes
A R T I C L E S
Figure 2. CD (a, c, e, and g) and UV-vis spectra (b, d, f, and h) of 3a-d in THF: blue line, original spectra of trans-isomer; pink line, PSS at 365 nm
(excess cis); green line, PSS at 436 nm (excess trans).
Figure 3. (a) CD (a, c, e, and g) and UV-vis spectra (b, d, f, and h) of 7a-d in CHCl3: blue line, original spectra of trans-isomer; pink line, PSS at 365
nm (excess cis), green line, PSS at 436 nm (excess trans).
that the ortho sulfoxide was not able to transfer the chirality so
efficiently. Upon irradiation of 7a-d at λ ) 365 nm, the
sulfoxide band remained unaltered, whereas a positive Cotton
effect appeared at 450 nm when the PSScis was reached. This
was especially remarkable in the cases of 7a and 7d (Figure 3a
and g, pink line). Again, reverse CD spectral changes occurred
after irradiation at 436 nm for 20-45 min.
To demonstrate that the sulfoxide directly linked to the aro-
matic ring was responsible for the chiral perturbation observed
in the azo group, we evaluated the behavior of [S(R)]-2′,4′,5′,6′-
tetrafluoro-4′-trifluoromethyl-4-(p-tolylsulfinyl)methyl azoben-
zene 8, a related enantiopure azocompound with the sulfoxide
separated by a CH2 from the azo aromatic core. Compound 8
was obtained, as previously reported,24 from [S(R)]-4-[(p-
9
J. AM. CHEM. SOC. VOL. 129, NO. 22, 2007 7093

A R T I C L E S
Carren˜o et al.
Scheme 4. Synthesis of [S(R)]-2′,4′,5′,6′-Tetrafluoro-4′-
trifluoromethyl-4-[(p-tolylsulfinyl)methyl] Azobenzene 8 and CD (a)
and UV-Visible Spectra (b) in 0.75 mM THFa
Table 1. Values of [R]20 (iPrOH) and HPLC Analysis of
D
[S(S)]-3a,b,d and [S(S)]-7a,b,d
PSScis
PSStrans
(irradiation at
436) trans:cis/
(time (h))
(irradiation at
initiala
initiala
trans/cisb
λ
365) trans/cis/ PSScis
λ
b
entry azo
[
R 20
]
(time (h))
[
R 20
]
∆[ ]
R 20
D
D
D
1
2
3
4
5
6
3a +411 66:34c
3b +355 35:65c
3d +228 65:35c
7a
7b -211 100:0e
7d
+16 90:10d
16:84/(2)
0:>99/(4)
13:87/(2)
33:67/(2)
67:33/(1)
25:75/(2)
+671 260
+611 246
+556 328
+187 204
65:35/(1)
40:60/(3)
68:32/(3)
73:27/(2.5)
75:25/(1.5)
67:33/(2)
-17 100:0d
+83
294
+551 535
a Optical rotation and HPLC were recorded immediately after preparation
of the corresponding solution of 3 or 7; solvent iPrOH, c ) 0.018. b Same
solvent and c than the initial [R]20
.
c Chiralpack OD column, hexane/iPrOH
D
.
(80/20) as eluent, 0.6 mL min-1
(95/5), 0.6 mL min-1
0.5 mL min-1
d Chiralpack OD column, hexane/iPrOH
i
.
e Chiralpack +AD column, hexane/ PrOH (90/10),
.
resulted (Table 1, entries 1 and 3). Similar initial trans/cis ratios
were regained by irradiation at λ ) 436 nm. Perfluorophenyl
azo derivative 3b, having the initially higher ratio of cis isomer
(35:65 trans/cis), evolved into a PSScis with a > 99% of cis
a Blue line, original spectra of trans-isomer; pink line, PSS at 365 nm
(excess cis); green line, PSS at 436 nm (excess trans).
isomer and a specific optical rotation of [R]20 ) +611 and
D
tolylsulfinyl)methyl]-4-hydroxy-2,5-cyclohexadienone 10,42 by
reaction with perfluorotolyl hydrazine 2c (Scheme 4). The UV-
vis spectrum of 8 displayed similar bands than 3 and 7. Upon
irradiation at 365 and 436 nm, UV-vis spectra showed the
typical variation of the trans to cis photoisomerization. In
comparison with the sulfinyl azocompounds 3 and 7, no changes
were evident in the CD spectra after irradiation at 365 and 436
nm (Scheme 4a) which suggested that, although photoisomer-
ization occurred, the lack of conjugation between the stereogenic
sulfur and the aromatic azo core was interrupting the chiral
perturbation of the NdN in both trans and cis isomers of 8.
The trans/cis ratio of the photostationary states of representa-
tive 3a,b,d and 7a,b,d were analyzed by HPLC.43 Specific
optical rotation ([R]20D) values were also measured simulta-
neously with the chiral HPLC analysis, before and after
irradiation, ensuring a correct interconnection between the trans/
cis ratio and the [R]20 observed. The initial values of [R]20
reisomerized upon irradiation at 436 nm into a 40:60 trans/cis
mixture (Table 1, entry 2). The 2′,5′-difluoro derivative 7a
(initial [R]20 ) -17) and 2′-CF3 derivative 7d (initial [R]20
D
D
) +16) reached a PSScis having a 33:67 (7a) and 25:75 (7d)
mixture of trans/cis isomers. Again the specific optical rotation
becomes higher while increasing the percentage of the cis isomer
(Table 1, entries 4 and 6). This effect was outstanding in the
case of 7d whose PSScis showed an [R]20 ) +551 (Table 1,
D
entry 6). Reisomerization afforded new photostationary states
similar to the initial. Contrary to the regioisomer 3b (Table 1,
entry 2), the perfluorophenyl 2-p-tolylsulfinyl azo derivative 7b
was somewhat difficult to isomerize, resulting in a 67:33 mixture
of trans/cis isomers after 1 h irradiation (Table 1, entry 5).44
Despite this low cis conversion, the variation of the specific
optical rotation was of similar order than the other azo
derivatives studied, varying from a negative [R]20 ) -211
D
D
D
value to a positive [R]20 ) +83 (∆[R]20 ) 294). Finally,
D
D
given in Table 1, correspond to the specific optical rotation of
irradiation at 436 nm gave a 75:25 mixture of trans/cis-7b. From
these HPLC analyses we can establish that the photoisomer-
ization occurs on both regioisomeric sulfinyl azocompounds 3a,
b, and d and 7a, b, and d. In comparison, higher ratios of cis
isomers were reached from the 3-sulfinyl azo derivatives 3.
Variations of [R]20D values were similar for both systems upon
reaching the PSScis states, with a significant increase around
250. Among the cases considered, the o-CF3 substituted
azobenzenes 3d and 7d displayed the higher [R]20D changes from
i
the azocompound 3 or 7 using PrOH as solvent and a
concentration of c ) 0.018. The samples were carefully prepared
in the dark to avoid trans to cis isomerizations. However, in
the case of azo derivatives 3, the HPLC analysis revealed that
in the initial stage, the iPrOH solution already had a considerable
proportion of the cis isomer, especially remarkable in the case
of azo 3b, where an initial 35:65 trans/cis ratio was evident
(Table 1, entry 2). The PSScis [R]20 represent the specific
D
optical rotation values of the azocompound after irradiation (400
W Hg lamp) at 365 nm for the time indicated in each case.44
The first HPLC analysis of the 2′,5′-difluoro and 2′-CF3-3-
(p-tolylsulfinyl) azobenzenes 3a and 3d showed a 66% and a
PSStrans to PSScis (∆[R]20 328 and 535, respectively).
D
Although the photoisomerization process occurred always, the
CD spectra evidenced different chiroptical responses in both
regioisomers. The origin of this difference could be in the
twisted molecular shape of trans-3c (X-ray crystal structure,
Figure 1a), where the transfer of chirality to the NdN group
observed in the CD spectra (transition π f π* at ca. 360 nm,
see Figure 2e) could be reinforced somewhat by the helicity.
The planar structure of trans-7b (Figure 1b) could explain the
lack of a significant positive Cotton effect in the region of the
azo absorption. The positive band of the n f π* transition
observed at λ ) 430 nm in the CD spectra of both enantiopure
cis-3 and cis-7 must be associated to a bent structure of the cis
65% of the trans isomer with an initial [R]20 value of +411
D
(3a) and +228 (3d). Upon irradiation a 16:84 (3a) and 13:87
(3d) mixture of trans/cis, with higher specific optical rotations
(42) (a) Carren˜o, M. C.; Pe´rez-Gonza´lez, M.; Ribagorda, M.; Houk, K. N. J.
Org. Chem. 1998, 63, 3687-3693. (b) Carren˜o, M. C.; Pe´rez Gonza´lez,
M.; Fischer, J. Tetrahedron Lett. 1995, 36, 4893-4896.
(43) The elution order is trans-3a (14.92 min), cis-3a (21.70 min), trans-3b
(13.12 min), cis-3b (16.51 min), trans-3d (13.51 min), cis-3d (22.15 min),
trans-7a (27.22 min), cis-7a (32.69 min), trans-7b (20.66 min), cis-7b
(41.98 min), and trans-7d (29.39 min), cis-7d (34.91 min).
(44) Longer irradiation times gave same trans/cis ratio.
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7094 J. AM. CHEM. SOC. VOL. 129, NO. 22, 2007

Photoinduced Conformational Switch of Azobenzenes
A R T I C L E S
Figure 5. NOESY NMR analysis of the 5-bromo-2-p-tolylsulfinyl azoben-
zene 7d.
Figure 4. Possible conformations of trans and cis isomers of 2- or
3-substituted azobenzenes.
azobenzene. Taking into account the invariable CD spectrum
of sulfinylmethyl azo-8, before and after photoisomerization
(Scheme 4), it seems important as well to have the sulfoxide
directly bonded to the aryl azo structure. Regarding the CD
spectra of the PSScis of 7, it is noteworthy to mention that the
lower cis ratio observed in the photoisomerization process of
7b (67:33 trans/cis) could also explain the modest variation
observed in the PSScis CD spectrum (Figure 3c) compared with
7a and 7d (Figure 3a and g). From all these results, we can
conclude that the position of the chiral sulfoxide on these
systems has a notable influence on the overall chirality and the
E/Z isomerization of the azo moiety, more significant in both
E and Z isomers of the meta-substituted systems 3. For the ortho-
sulfinyl substituted analogues 7, the chiroptical properties of
the azo moiety stand out only in the Z isomers. Additionally,
photoisomerization of regioisomers 3 is more efficient than that
of 7, reaching always better cis conversions. The associated bent
structure of the Z isomer of azobenzenes always displayed higher
values of optical rotation in both azo sulfoxides.
Figure 6. S-shaped and U-shaped geometry of cis p-tolylsulfinyl azoben-
zenes 7b and 3c.
the 1,3-parallel orientation with the NdN double bond is
showing a steric interaction between R and the azo group, and
should be less stable. Regarding the possible conformations for
the cis isomer and assuming the favored bent structure, where
one aryl ring is in the edge-face of the other, we should consider
three different rotamers. The conformation labeled cis-A, which
disposes the R substituent under the aromatic ring-II situated
out of the plane, must be sterically congested. In such a
disposition, in the NMR spectra, the chemical shift of the R
substituent should be suffering the anisotropic influence of
ring-II. Conformer cis-B is alleviating this steric congestion
by placing the R substituent far from the influence of ring-II
and the azo group. In this case, the hydrogens of ring-I must
be under the influence of the orthogonal ring-II. Finally, a
third conformer cis-C with the aromatic ring-I out of the plane,
must be considered. In this case, the anisotropic effect should
be observed in the chemical shift of the hydrogens of ring-II
(Figure 4).
Photoisomerization NMR Studies. To gain a deeper insight
into the geometry adopted by the trans and cis isomers we next
examined the photoisomerization of 3 and 7 by 1H NMR
spectroscopy in CDCl3. It is empirically known that cis
azobenzenes present a nonplanar structure, owing to the close
proximity of the aromatic rings.5g,12-14 Caused by this bent
1
structure, H NMR of the trans f cis isomerization exhibits a
For the shake of clarity, the discussion of the possible
conformations of the sulfinyl azoderivatives, will be referred
to the trans and cis type conformations depicted in Figure 4,
considering that the R susbtituent is the SOp-Tol.
characteristic upfield shift of the aromatic protons.45 Before
discussing the effects found in the NMR study of 3 and 7, it is
important to analyze all the conformations that can be found in
the differently substituted achiral azobenzenes. Unsubstituted
or symmetrically substituted azobenzenes such as para-disub-
stituted aromatic derivatives present a unique conformer for the
trans and cis isomers. It has been reported that symmetrically
2,3-disubstituted azobenzenes can present up to three different
conformations for the trans and cis isomers.46 However, a
detailed conformational analysis of an azobenzene bearing
different substitution pattern in both aryl groups at ortho or meta
positions has not been reported. Such azobenzenes can display
up to three conformations for each isomer. In Figure 4 we have
represented all the possible conformations of a general situation
for a 2- or 3-substituted azobenzene. The conformer labeled
trans-A, which displays the ortho R (or meta R) substituent in
the opposite direction of the azo group, is more rodlike shaped.
The trans-B conformer with the ortho or meta R substituent in
The X-ray crystal structure of trans-7b (Figure 1) revealed
that, in the solid state, the trans-A disposition and the s-cis
conformation around the C-S bond are preferred. To monitor
the photoisomerization of 3 and 7 by 1H NMR, spectra of 0.01
M solutions in CDCl3 were recorded before and after irradiation
with a 400 W Hg lamp at 365 nm.47 In all cases, but one, the
mixture resulting after irradiation ranged between 70:30 and
55:45 trans/cis. The chemical shifts of the more significant
protons for the conformational study of the trans and cis-isomers
of 3c are summarized in Scheme 5.
The spectrum of trans-3c discloses a noteworthy deshielding
for H-2 (δ ) 8.60 ppm), which is in accordance with the 1,3-
parallel disposition of the sulfinylic oxygen with respect to the
vicinal H-2,48 observed by X-ray diffraction (Figure 1). After
(45) Chambers, S. M.; Hawthorn, I. S. J. Chem. Soc., Chem. Commun. 1994,
1631-1632.
(46) For a similar trans-cis conformational analysis with symmetrically 2,3-
disubstituted azobenzene see: Ruslim, C.; Ichimura, K. J. Mater. Chem.
1999, 9, 673-681.
(47) For spectra details of the photoisomerized azocompounds see Supporting
Information.
(48) (a) Foster, A. B.; Inch, T. D.; Qadir, M. H.; Weber, J. M. J. Chem. Soc.,
Chem. Commun. 1968, 1086-1087. (b) Cook, M. J. Kem. Kemie 1976, 3,
16.
9
J. AM. CHEM. SOC. VOL. 129, NO. 22, 2007 7095

A R T I C L E S
Carren˜o et al.
Scheme 5. 1H NMR Analysis of the Photoisomerization of 3c
Scheme 6. 1H NMR Analysis of the Photoisomerization of 7b
irradiation, an exceptionally high ratio of cis isomer (trans/cis
of 20/80) was formed. All the signals suffer the expected
shielding in the cis-3c isomer. It should be pointed out that H-2
exhibits the highest upfield shift (H-2 δtrans ) 8.60 moves to
δcis ) 7.49 ppm, ∆δcis/trans ) -1.11 ppm) (Scheme 5). Sur-
prisingly, despite the apparent distance between the p-tolyl group
of the sulfoxide and the other aromatic rings, the AA′ hydrogens
of the AA′BB′ system of cis-3c, suffered a significant upfield
shift and appeared at δcis ) 7.19 ppm (∆δcis/trans ) -0.42 ppm).
These observations suggested a preferred conformation situating
the perfluorotolyl ring-II in the edge-face of the p-tolylsulfinyl
group. This is a cis-A type conformation (Figure 4, R ) SOp-
Tol and Scheme 5) which from the steric point of view was
not expected to be stable. Although the conformer cis-B,
situating the sulfoxide outside the influence of the perfluorotolyl
ring, was expected to be more favorable from the steric point
of view, the NMR parameters observed did not match with the
distance existing between the p-tolyl ring of the sulfoxide and
the perfluorotolyl ring-I in such a conformation. According with
these observations, the sulfoxide is defining a particular rigid
conformer in both the trans-3c and cis-3c, the latter adopting a
U shape, which could be essential for further applications.
conformation, only H-6 of the 2-p-tolylsulfinyl aryl-substituted
ring-I suffers the anisotropic effect of the ring-II.
Comparing the structures of the cis sulfinyl derivatives 3c
and 7b, a very different disposition of the sulfoxide aromatic
ring with respect to the perfluoro aryl substituent in the cis-
bent structure is evident. Thus, while the conformation of
azobenzene cis-3c approaches the p-tolyl group to the perflu-
orinated moiety adopting U-shaped geometry, the conformation
of cis-7b is an S shape, situating the p-tolyl group far from the
perfluorinated ring (Figure 6).
1
The H NMR spectrum of 2-p-tolylsulfinyl azocompound
trans-7d showed two singlets at δ 7.77 ppm and δ 8.06
corresponding to H-3 and H-6 of the sulfoxide bearing ring-(I).
The unequivocal assignment of H-3 was based on the NOE
effect observed between the proton appearing at δ ) 7.77 ppm
and the signal of the MeO group at δ ) 4.14 ppm,46 and the
AA′ part of the AA′BB′ p-tolyl system appearing at 7.50 ppm
(Figure 5a). After photoisomerization of 7d, two new singlets
appeared at δ ) 7.82 and 6.26 ppm corresponding to H-3 and
H-6, respectively. These signals were similarly assigned from
NOESY NMR experiments (Figure 5b).49
The most significant 1H NMR data of both trans- and cis-7b
are included in Scheme 6. Only H-6 suffered the expected
upfield shift of the aromatic hydrogens in the isomer cis-7b
(δtrans ) 8.05 to δcis ) 6.60 ppm : ∆δcis/trans ) -1.45 ppm),
whereas an unusual small deshielding effect resulted for H-3
(∆δcis/trans ) 0.02 ppm) and the AA′BB′ system of the p-tolyl
group (AA′: ∆δcis/trans ) 0.15 ppm). These observations are
consistent with the cis-7b isomer having a conformation of type
cis-B represented in Scheme 6, where the perfluorophenyl
aromatic ring-II is out of the plane of the azo group, in the
opposite side of the p-tolylsulfinyl substituent. In such a
The study of azo compounds 3a and 7a, or 3d and 7d, with
an dissymmetrically substituted 2′,5′-difluorophenyl or 2′-CF3
moiety in the azobenzene, provided information about how the
asymmetric substitution pattern in the aryl ring-II affected the
conformation of trans and cis isomers. Here again, we have to
consider that the presence of a second ortho or meta substituent
in the ring-II increases the number of possible conformations.
Therefore, following the same criteria, differently 2,2′- or 3,2′-
disubstituted or 2,2′,5′- or 3,2′,5′-substituted azobenzenes could
display up to four conformers for each trans and cis isomers.
Conformers trans-E, trans-F, and trans-G depicted in Figure 7
show at least one destabilizing interaction R/NdN, whereas in
conformer trans-D such interaction is not present. Conformers
existent in the cis isomers could situate ring-II (Figure 7, cis-D
and cis-E) or ring-I (Figure 7, cis-F and cis-G) out of the plane
containing the azo group. The effects of the orthogonal rings
on the chemical shifts of the aromatic substituents under their
influence must be noticed on the R substituents of ring-I in
cis-D and on the R′ substituent of ring-II in conformer cis-F.
The hydrogens of the rings I and II in conformers cis-E
and cis-G, respectively, must also suffer the anisotropic effect
of the orthogonal aromatic ring-II. For later discussion, we
(49) Similar NOE effects were observed for 7b and 7e (see Supporting
Information).
9
7096 J. AM. CHEM. SOC. VOL. 129, NO. 22, 2007

Photoinduced Conformational Switch of Azobenzenes
A R T I C L E S
Figure 7. Conformers of trans and cis isomers of 2,2′- or 3,2′-disubstituted or 2,2′,5′- or 3,2′,5′-substituted azobenzenes.
Scheme 7. 1H NMR Analysis of the Photoisomerization of 3a
labeled ring-I to the p-tolylsulfinyl-substituted aryl group (R )
SOp-Tol) and ring-II to the fluorine-bearing aryl moiety (R′ )
R′′ ) F for 3a and 7a and R′ ) CF3 and R′′ ) H for 3d and
7d).
ppm), while H-3′ and H-4′ appeared together as a multiplet at
δcis ) 6.90-6.86 ppm, with a moderate shielding effect of
∆δcis/trans ) -0.34 and -0.25 ppm, respectively (table ring-II
in Scheme 7). The high shielding effect observed for H-2 of
ring-I in cis-3a could match with a cis-D-type conformation
placing the 2′,5′-difluorophenyl ring-II in the edge-face of the
p-tolylsulfinyl group, where H-2 is under the influence of the
anisotropic effect of ring-II. The shielding effect observed in
H-6′ (aryl group-II) which appeared at δcis ) 6.74 ppm, could
suggest another cis conformer that situates the sulfinyl substi-
tuted ring-I out of the plane containing the azo group (cis-G
(3) in Figure 9).
We started the NMR analysis with azo derivatives 3a and
3d. The 1H NMR parameters of trans-2′,5′-difluoro-substituted
azocompound 3a were similar to those observed for 3c. Thus,
the chemical shifts of the hydrogens of ring-I appeared at δH-2
) 8.60, δH-6 ) 8.03 and δH-5 ) 6.97, (table of ring-I in Scheme
7). The assignment of the aromatic hydrogens of the 2′,5′-
difluoro aryl-substituted ring-II (δH-6′ ) 7.48, δH-4′ ) 7.25-
7.20, δH-3′ ) 7.15-7.11) was based on the 19F,1H heteronuclear
overhauser spectroscopy (HOESY) and double resonance (H,H)
NMR experiments.47 The 19F,1H HOESY spectrum of trans-3a
exhibited two cross-peaks between the fluorine atom at -117.5
ppm and the signals appearing at δ ) 7.48 and δ ) 7.15-7.10
ppm, that should correspond to the interaction between F-5′ with
H-6′ and H-4′ (Figure 8a). 19F signal at -129 ppm showed only
In such disposition, the hydrogens of ring-II would suffer
the anisotropic effect of the orthogonal aromatic moiety (I), but
it would not justify the high shielding observed for H-2 (∆δ )
-1.22 ppm). This key observation led us to consider that the
p-tolyl group of the sulfoxide was again playing an important
role in the conformation of the cis -3a isomer, fixing the sulfinyl
oxygen and H-2 in a 1,3-parallel disposition, providing an
additional rigidity to the azo system, and leaving the p-tolyl
group outside of the plane. In such a U-shaped disposition, one
of the edge-faces of the substituted aryl ring-II can suffer the
anisotropic π-cloud effect of this p-tolyl group. When this aryl
ring-II is differently substituted, like in the case of 3a, two
possible conformations (cis-D and cis-D′) can be considered
(Scheme 7). Thus, the cis-D-type conformation, situating the F
at C-2′ (R′) substituent far from the p-tolyl influence, will shield
the H-6′ and H-5′ ring-II protons, whereas in the cis-D′
conformation this effect will turn over H-3′ and the F at C-2′
(R′) substituents. The upfield shift observed for H-6′ in the
difluorophenyl substituted ring-II of cis-3a suggested the major
participation of conformer cis-D where the p-tolyl group is
oriented to exert its anisotropic effect directly on the edge face
containing H-6′.
1
one NOE interaction with the H-signal at 7.25-7.20 ppm,
which consequently were assigned to F-2′ and H-3′, respectively.
Additionally, the hydrogen signal at δ ) 7.48 ppm (ddd, J )
9.0, 5.1, and 3.1 Hz) displayed the typical coupling constants
1
2
2
values of a J ortho (H,F) (8.9 Hz), J meta (H,F) (5.7 Hz), J
meta (H,H) (1-3 Hz),50, and therefore it was assigned to H-6′.
The NMR data for cis-3a are also depicted in Scheme 7. All
the protons appeared more shielded than in trans-3a, but the
hydrogen cis-H-2 is suffering the highest shielding effect
(∆δcis/trans ) -1.22 ppm). The signals corresponding to the
protons of ring-II were also assigned on the base of 19F,1H
HOESY (Figure 8b) and double resonance experiments.47
A considerable upfield shift was observed for proton H-6′
after photoisomerization (δcis ) 6.74 ppm, ∆δcis/trans ) -0.73
(50) Prestsch, E.; Bu¨hlmann, P.; Affolter, C.; Herrera, A.; Mart´ınez, R. In
Structure Determination of Organic Compounds; Springer-Verlag: Berlin,
Heidelberg, New York, 2004.
9
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A R T I C L E S
Carren˜o et al.
Figure 11. HOESY 19F-1H NMR analysis of the 2-p-tolylsulfinyl azoben-
zene 7d.
Figure 8. HOESY 19F-1H NMR analysis of the 3-p-tolylsulfinyl azobenzene
3a.
Scheme 8. 1H NMR Analysis of the Photoisomerization of 3d
Figure 9. The cis-G conformation of 2′,5′-substituted sulfinyl azobenzenes
3 and 7.
those observed for the perfluorophenyl derivative 7b (Scheme
6). The conformation cis-E represented in Scheme 9 for cis-7a
and in Scheme 10 for cis-7d justifies the high shield observed
for H-6 (∆δcis/trans ) -1.64 and -1.75, respectively) owing to
the effect of the π-cloud of the fluorinated aryl ring-II situated
out of the plane. The assignment of the hydrogens of ring-II
both in trans-7a and cis-7a was based on double resonance
(H,H) experiments and the values of the coupling constants
(J(H,F) and J(H,H)) measured in the 1H NMR spectra.46 In the
case of cis-7a, it is noteworthy that proton H-6′ also suffered a
considerable shielding effect (∆δcis/trans ) -1.79 ppm), while
Figure 10. HOESY 19F-1H NMR analysis of the 3-p-tolylsulfinyl azoben-
zene 3d.
Concerning the 2′-CF3-3-p-tolylsulfinyl azobenzene-3d, the
most significant changes observed in the chemical shifts of the
ring-I protons in the photoisomerization process, are shown in
Scheme 8 (Table Ring-I). Unfortunately, the assignment of all
the protons of the trifluoromethylphenyl ring-II was difficult
to pursue, because of their proximal δ values. Nevertheless, as
shown in Figure 10a, the 1H,19F HOESY spectrum of trans-3d
revealed a cross-peak between the 19F signal at -57.6 ppm and
H-3′ and H-4′ present a more moderate effect of ∆δcis/trans
)
-0.28 and -0.34 ppm, respectively [Table Ring-II in Scheme
9]. All these data matched with the fixed conformation cis-E
for 7a, where the p-tolyl group of the sulfoxide was again
playing an important shielding role over H-6′. We also
considered the conformer placing the ring-I outside the plane,
(Figure 9 cis-G (7), R′ ) CF3 and R′′ ) H) but, as mentioned
before, this conformation would not justify the upfield shift
observed for H-6. As shown in Scheme 9, a second conformer
like cis-E′ with a different orientation of ring-(II) could be
considered for cis-7a, but in such a disposition the high shielding
observed for H-6′ could not be justified (Scheme 9).
1
the H signal at δ ) 7.84-7.80 ppm which corresponded to
two hydrogens belonging to ring-II.47 This (H, F) NOE effect
allowed us to assign H-3′ of trans-3d to one of the hydrogens
appearing at δtrans ) 7.84-7.80 ppm. Besides the expected
chemical shift changes of the ring-I in cis-3d (Table Ring-I,
δcis in Scheme 8), the most significant feature was again the
presence of an upfielded signal at δ ) 6.29-6.27 ppm and two
additional cis-signals at δ ) 7.77-7.76 and 7.32-7.30 ppm.
The 19F,1H HOESY spectrum of cis-3d revealed a 19F signal at
-60.5 ppm displaying a NOE interaction with the 1H signal at
δ ) 7.77-7.76 ppm, integrating for 1H, which was then
assigned to cis-H-3′ (Figure 10b). Therefore, the new shielded
signal appearing at δ ) 6.29-6.27 ppm should match with H-4′,
H-5′, or H-6′ protons. By analogy with the upfield shift observed
for H-6′ in cis-3a, we assigned the signal at 6.29-6.27 ppm to
H-5′ or H-6′. On the basis of these data, we also assumed that
azocompound cis-3d adopted the cis-D type conformation shown
in Scheme 8, where the ortho-CF3 ring-II substituent is placed
far from the anisotropic influence of the p-tolyl group of the
sulfoxide, and therefore its effect will lay into the H-6′-H-5′
edge face of ring-II.
In the case of 7d (Scheme 10) the unequivocal assignment
of all the hydrogens of ring-II (H-3′, H-4′, H-5′, and H-6′) was
more difficult. The 19F,1H HOESY spectrum of trans-7d
revealed two cross-peaks between the 19F signal at -57.5 ppm
1
and the H signals at 7.89 ppm (d, J ) 7.7 Hz, 1H), assigned
to H-3′, and 8.01 ppm (s, 1H), assigned to H-6 of ring-I (Figure
11a). Upon photoisomerization the 19F signal of cis-7d at -60.5
1
ppm displayed a NOE interaction with the H signal at 7.73
ppm (d, J ) 8 Hz, 1H), thus attributed to cis-H-3′. In this case,
the more shielded signal of ring-II appeared at 4.92 ppm (brd,
J ) 8 Hz, Scheme 10, Table Ring-II). Another significant feature
of cis-7d corresponded to the aryl ring-II hydrogen observed at
7.05 ppm (brt, J ) 7.7 Hz) which matched H-6′ with the doublet
appearing at 4.92 ppm, that should have an ortho coupling
constant J(H,H) with the vicinal H-5′. In turn, H-5′ was assigned
to the triplet at 7.05 ppm, showing two ortho-J(H,H) coupling
constants. With all these data, we can conclude that the shielding
A similar NMR study of 7a and 7d evidenced the variations
of chemical shifts depicted in Schemes 9 and 10, respectively,
for the most significant protons of cis and trans isomers. All
1
the H NMR signals of sulfinyl substituted ring-I and protons
of the AA′ tolyl system suffered trans to cis changes similar to
9
7098 J. AM. CHEM. SOC. VOL. 129, NO. 22, 2007

Photoinduced Conformational Switch of Azobenzenes
A R T I C L E S
Scheme 9. 1H NMR Analysis of the Photoisomerization of 7a
Scheme 10. 1H NMR Analysis of the Photoisomerization of 7d
Table 2. Helical Twisting Power (â) of Enantiopure Dopants 3d
and 7d in E7 for the Trans Configuration and the Photostationary
Composition after Irradiation at 365 and 436 nm
1
a
â (µ )
m-
PSS
PSS
dopant
pure E
(λ
365 nm)
(
λ
436 nm)
3d
7d
-39.5
-16.4
-26.4
-7.9
-34.7
-15.9
a â ) (pcee)-1, where p is the pitch of the cholesteric, c is the molar
fraction of the dopant and ee its enantiomeric excess; see ref 18.
solvents offers the possibility to control the supramolecular
chirality of a cholesteric phase, and this property can be applied
in all optical devices.51 The azobenzene moiety is the most
frequently applied photoactive bistable group in liquid crystal
research.19c,21a,b,52 In fact, because of the large differences in
structure, the helical twisting power of trans and cis isomers
are usually quite different which allows efficient modulation
of the cholesteric pitch. The behavior of our chiral switches as
dopants for liquid crystals was studied with enantiopure 2′-CF3
aryl azocompounds 3d and 7d, which had displayed the higher
changes in the CD spectra upon photoisomerization. Com-
mercially available nematic solvent E7 was used. Concentrations
of 3d and 7d are indicated in Table 2, together with the â values
obtained for the trans-azo derivatives and the two photostation-
ary states produced upon irradiation. In comparison with other
centrally chiral azo derivatives, enantiopure sulfinyl compounds
3d and 7d exhibited a significant twisting power of -39.5 and
-16.4 µm-1, respectively. Irradiation at 365 nm decreased the
relative â value [â (3d) ) -26.4 µm-1 and â (7d) ) -15.9
µm-1], while subsequent irradiation at 436 nm reverted to -34.7
and -15.9 µm-1, respectively. Both enantiopure azobenzenes
showed a negative screw sense of the cholesteric packing
induced by the [S(S)]-p-tolylsulfinyl stereogenic center. The
relationship between the negative â values of some alkyl aryl
sulfoxides (measured in E7 nematic phase) and the [S(S)]-
configuration of the stereogenic sulfur atom has been reported,23
however no studies have been made with bisaryl sulfoxides.
Our previous results indicate that this correlation between the
negative â value and the [S(S)]-configuration endure as well in
the cases of the bisaryl sulfoxides 3d and 7d. It is worthy to
effect observed for H-6 (ring-I) in cis-7d is due to the π-cloud
of the fluorinated aryl ring-II, while the upfield shift of H-6′
(ring-II) is a consequence of the anisotropic effect of the p-tolyl
ring, in the conformer cis-E represented in Scheme 10.
All the information deduced from the NMR data indicated
that once the photoisomerization process had occurred, the
orientation of the cis-azobenzene in both regioisomers 3 and 7
is controlled by the p-tolylsulfinyl group situated at C-2 or C-3.
When the sulfoxide is placed at C-3 of ring-I (azocompounds
3), the trans to cis photoisomerization of the NdN double bond
leaves the ring-II preferentially toward the edge-face of the 3-p-
tolylsulfinyl substituent leading to a U-shaped disposition of
the three aromatic rings. The preferred orientation after NdN
photoisomerization of 2-sulfinylazobenzenes 7 is situating the
p-tolyl group toward the edge-face of the ring-II. The favored
fixed 1,3-parallel disposition of the sulfinyl oxygen with respect
to the vicinal H-2 or H-3 hydrogens (in 3 or 7, respectively) is
the origin of the final stable ordered geometries observed for
the trans and cis isomers. In both 3 and 7, when an ortho
substituent is present in the aryl ring-II, this substituent is
projected far from the anisotropic effect of the p-tolyl group of
the sulfoxide.
(51) (a) Ichimura, K. Chem. ReV. 2000, 100, 1847-1874. (b) Ikeda, T.;
Kanazawa, A. In Molecular Switches; Feringa, B. L., Ed.; Wiley-VCH:
Weinheim, Germany, 2001; pp 363-397. (c) Eelkem, R.; Feringa, B. L.
Org. Biomol. Chem. 2006, 4, 3729-3745.
(52) Yoshioka, T.; Alam, M. D. Z.; Ogata, T.; Nonaka, T.; Kurihara, S. Liq.
Cryst. 2004, 31, 1285-1291.
Photomodulation of Cholesteric Liquid-Crystalline Meso-
phases. As the helical sense and pitch of an induced cholesteric
phase are dependent on the (isomeric) state of the dopant, the
incorporation of a photoswitchable molecule in nematic LC
9
J. AM. CHEM. SOC. VOL. 129, NO. 22, 2007 7099

A R T I C L E S
Carren˜o et al.
mention that the presence of the sulfoxide at the azobenzene
produced a significant increase of the helical twisting power
compared with the â values reported for simple alkyl aryl
sulfoxides (around -10 to -1.1 in E7 nematic phase). Once
again, considering the different position of the sulfoxide at C-2
or C-3 of the aryl moiety of the azocompound, better results
were obtained from the 3-sulfinyl azo derivative 3d which
displayed a bigger â value than 7d.
azobenzene (ortho or meta to the NdN), a conformational
change could be induced in a controlled manner by irradiation.
The presence of such a chiral p-tolylsulfinyl group in the
azobenzene is acting as a stem in a sunflower, where upon light
exposure phototropy is induced. The overall disposition of the
systems can be controlled by the C-2 or C-3 sulfinyl substitution
during the trans to cis NdN double bond isomerization. As a
result, a photomodulable molecular switch with a particular rigid
and compact conformation and chiral response has been
described. The easy and reversible change observed between
the different conformational states could find applications in
the photocontrol of several molecular processes. Finally, two
sulfinyl azobenzenes were tested as chiral dopants in nematic
LC systems, showing interesting â values for such centrally
chiral azocompounds and a notably photoisomerization process
in a liquid crystalline cholesteric phase.
Conclusion
In summary, we have succeeded in the regioselective
synthesis of new optically pure 2- or 3-p-tolylsulfinyl azoben-
zenes, from commercially available arylhydrazines and p-
tolylsulfinyl functionalized p-quinone bisketals. Reaction always
occurs by preferential attack of the arylhydrazine to the less-
hindered ketal group. The presence of a 4-bromo substituent in
the 1-p-tolylsulfinyl-p-quinone dimethyl bisketal allowed the
regiocontrolled preferential attack at the ketal group close to
the sulfoxide giving rise to 2-p-tolylsulfinyl azobenzenes 7. The
study of their photoresponsive behavior by CD, evidenced that
the position of the sulfoxide group in the azobenzene causes
two different chiral responses. Thus, the presence of the
p-tolylsulfinyl group at C-3 induced a transfer of chirality from
the stereogenic sulfur to the NdN group in both the trans and
cis isomers, while when the sulfoxide is at C-2, this transfer of
chirality only occurred in the cis-isomers. This different
chiroptical response is a consequence of a conformation fixed
by the sulfoxide, as deduced by NMR studies. Cis-isomers of
both sulfinyl azocompounds 3 and 7, show a complementary
disposition of the substituents around the NdN moiety. Thus,
choosing the appropriate location of the sulfoxide in the
Acknowledgment. This work is dedicated to Prof. Miguel
A. Yus on the occasion of his 60th birthday. We thank Direccio´n
General de Investigacio´n Cient´ıfica y Te´cnica (Grant CTQ2005-
02095/BQU), Accio´n Integrada Hispano-Italiana 2004-0027,
Comunidad de Madrid (GR/MAT/0152/2004), and Ministero
dell’Universita` e della Ricerca, Italy, (PRIN 2005) for financial
support. M.R. thanks Ministerio de Educacio´n y Ciencia for a
Ramo´n y Cajal contract and I.N. and E.M. for a fellowship.
Supporting Information Available: Detailed experimental
procedures and full characterization of all compounds. Copies
of selected 1H, 13C, 2D (H,H) (H,F) NMR spectra, HPLC, and
X-ray crystallography.
JA070163O
9
7100 J. AM. CHEM. SOC. VOL. 129, NO. 22, 2007