Dihydroazulene/Vinylheptafulvene Photoswitch: Ultrafast Back Reaction Induced by Dihydronaphthalene Annulation

Article abstract of DOI:10.1002/ejoc.201500320

The vinylheptafulvene (VHF) to dihydroazulene (DHA) electrocyclization is known to proceed from an s-cis conformation of VHF and cannot occur from the more stable s-trans conformation. Locking the VHF in the s-cis conformation by the introduction of a dih

Full text of DOI:10.1002/ejoc.201500320

FULL PAPER
DOI: 10.1002/ejoc.201500320
Dihydroazulene/Vinylheptafulvene Photoswitch: Ultrafast Back Reaction
Induced by Dihydronaphthalene Annulation
Søren Lindbæk Broman,*[a] Oleg Kushnir,[b] Martin Rosenberg,[a] Anders Kadziola,[a]
Joerg Daub,[b] and Mogens Brøndsted Nielsen[a]
Keywords: Pericyclic reactions / Cross-coupling / Photochromism / Fused-ring systems
The vinylheptafulvene (VHF) to dihydroazulene (DHA) elec-
trocyclization is known to proceed from an s-cis conformation
photoactive DHA isomer, now annulated to DHN, exhibited
a desired redshift relative to the parent compound. Here, we
of VHF and cannot occur from the more stable s-trans confor- present the synthesis and study of these DHN-DHA/VHFs,
mation. Locking the VHF in the s-cis conformation by the
introduction of a dihydronaphthalene (DHN) unit has been
found to greatly enhance the speed of this reaction. Thus,
the half-life was reduced by more than a factor of 150000
in cyclohexane and by a factor of approximately 950000 in
ethanol. In addition, the characteristic absorption of the
including a protocol for the incorporation of a pseudo-halide
to enable the further functionalization of the molecule by
metal-catalyzed cross-coupling reactions. For proof-of-con-
cept, two different sulfur end-groups were incorporated as
anchoring groups for potential molecular electronics
applications.
This light-induced ring-opening reaction from DHA to
VHF induces a large change in the molecule’s dipole mo-
ment,[8] elimination of the fluorescence of DHA,[9] a color
change from yellow to red/purple,[9,10] and an increase in
the system’s single-molecule conductance.[11] The system is
attractive as it rarely requires inconvenient precautions such
as water- or oxygen-free conditions and no photostationary
state is obtained as it is only photochromic in one direction
(T-type photoswitch). Although the ring-opening
(DHAǞVHF) is fast (1.2 ps),[12] the ring-closure
(VHFǞDHA) is relatively slow (t1/2 = 21–1545 min, 25 °C,
in MeCN),[9,10,13] but for most derivatives complete conver-
sion in both directions is usually ultimately observed. In
connection with materials science and molecular elec-
tronics, a DHA molecule has been trapped between two
silver electrodes in a single-molecule device operating in the
Coulomb blockade regime, and, by using light/heat (or by
regulating the bias potential), conductance modulation was
observed.[11a,11b] Although light-induced switching from
DHA to VHF in this device occurred almost instant-
aneously, the VHFǞDHA back reaction took several
minutes. A long half-life for this reaction could on one hand
be advantageous for some molecular electronics compo-
nents but on the other hand, relay components undergoing
fast VHFǞDHA conversions also present relevant targets.
The slow back-reaction is a consequence of the steric
bulk of the two cyano groups rotating the two double bonds
of the VHF out of the cycloheptatriene plane and thus
pushing C8 and C1 out of proximity. Also a favorable s-cis-
to-s-trans rotation around the single bond (C2–C3) is mov-
ing C8a and C1 further away from each other, thus pre-
Introduction
Photoswitches have been shown to exhibit many possible
applications in both the materials and biological sciences.
Although inherently different in switching mechanisms, the
three most popular photoswitches, azobenzene,[1] dithienyl-
ethene,[2] and spiropyran,[3] have been successfully applied
in these areas because of their reasonable quantum yields,
high and tunable photostationary state ratios, good fatigue
resistances, and synthetic accessibility. Recent impressive
developments include the ability to turn on and off the cata-
lytic function of artificial enzymes and to control peptide
folding,[4] the modulation of the molecule conductance both
on surfaces and in between electrodes,[5] and light-driven
systems with machine-like functions such as molecular
scissors or tweezers, pedals, lifts, and vehicles.[6]
Another example of a photochromic molecule is 1,8a-
dihydroazulene-1,1-dicarbonitrile (DHA).[7] Following light
irradiation at its lowest-energy absorption maximum (for
DHA 1a, ca. 353 nm), the molecule undergoes a retro-elec-
trocyclization to vinylheptafulvene (VHF) (Scheme 1),
which is evident by the formation of an often more intense
and redshifted absorption maximum at around 470 nm.
[a] Department of Chemistry, University of Copenhagen,
Universitetsparken 5, 2100 Copenhagen Ø, Denmark
E-mail: slb@kiku.dk
www.ki.ku.dk
[b] Department of Chemistry, University of Regensburg,
Universitätsstrasse 31, 93040 Regensburg, Germany
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201500320.
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S. L. Broman et al.
FULL PAPER
Scheme 1. Light-induced ring-opening of dihydroazulene (DHA) to
its corresponding metastable VHF, most stable in its s-trans con-
former. Inset: atomic numbering according to that of azulene.
Scheme 2. Light-induced ring-opening of CH-DHA 2a to its corre-
sponding sterically constrained metastable VHF 2b; s-cis/s-trans
rotation is inhibited.
venting the ring-closure reaction (Scheme 1; the s-cis/
s-trans notation refers to the highlighted butadiene moiety
of VHF).[14]
further functionalization of such systems. By employing
UV/Vis absorption spectrophotometry at low temperatures,
we were able to fully convert DHN-DHA (3a) into the cor-
responding VHF (3b) upon irradiation with light. This
short-lived VHF showed a dramatic increase in the rate of
ring-closure back to DHA of more than a factor of 150000
in cyclohexane and of approximately 950000 in EtOH com-
pared with that of VHF 1b. The DHA structures are shown
in Figure 1.
Despite this, by using a pulse-probe technique, it has
been shown that by delaying a 530-nm laser pulse by 25 ps
after a ring-opening 360-nm pulse, the resulting “VHF”
structure could be returned to DHA.[12b] This was possible
as the atoms are not allowed time to fully rearrange and
are still located as they are in DHA. Although the life-time
of the VHF can be fine-tuned by substitution with electron-
withdrawing and/or -donating groups at each end of the
molecule,[9a,10,13] a dramatic reduction of the life-time of the
VHF was observed by tethering C2–C3 using a cyclohexane
(CH) ring (Scheme 2).[15] Thus, steric constraints were
thought to “lock” the VHF in its s-cis conformation and
not only to inhibit rotation to its corresponding s-trans con-
former, but also to keep C8a and C1 in close proximity,
thereby accelerating the thermally induced back reaction.
Thus, a light-induced conversion of CH-DHA 2a into VHF
2b could be identified only (on a second timescale) at a very
low temperature (–60 °C in EtOH), at which too rapid a
back reaction is prevented.[15] It seems that the cyclohexane
ring has the appropriate length and geometry to enable the
largest orbital overlap in the VHF state. Thus, neither
VHFs with a fused cyclopentane nor a cycloheptane ring
show such
a fast ring-closure (half-lives Ͼ 6 h in
silicone[12a]). The photophysical properties of CH-DHA 2a
have not yet been investigated in detail, and for this reason
the life-time of the VHF 2b remains unknown. Because of
Figure 1. Structures of DHAs 1a–3a.
this
a
more thorough study of the photophysical
In addition, we report the careful synthesis of a pseudo-
properties of such fast-switching DHA/VHFs was deemed halogenated (triflate) derivative of DHN-DHA (4a). As the
necessary. We note that the use of steric constraints has initial attempt at incorporating an iodo substituent was not
successfully been used to significantly improve the switch- successful, a triflate substituent was used because triflates
ing speed of other photoswitches.[16]
also present a versatile functional handle for further
Here, we report the synthesis of a dihydronaphthalene elaboration. It was included to enable further functionaliza-
(DHN) annulated to DHA 3a, combining the rate-enhanc- tion to ultimately allow, in future work, the exploitation of
ing features of the six-membered ring and the higher sta- the ultrafast DHA/VHF couple in advanced systems. This
bility and redshift of the DHA absorption by forcing the could, as mentioned above, be in the field of molecular elec-
phenyl ring into co-planarity with the five-membered ring. tronics. For proof-of-concept we have used this triflate func-
The rationale behind the design of the targeted DHN-DHA tionality to incorporate such electrode anchoring groups as
3a is the general trend that aryl-functionalized DHA/VHFs SMe and SAc by Suzuki cross-coupling and Pd-catalyzed
show greater fatigue resistance (as lower-energy light is re- SNAr reaction protocols as these exact sulfur-containing
quired due to the redshifted absorption maximum) com- functional groups have already successfully been used to in-
bined with the well-established synthetic procedures for the corporate DHA/VHF into a device.[11]
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Dihydroazulene/Vinylheptafulvene Photoswitch
Results and Discussion
Synthesis
The synthesis of DHN-DHA 3a is shown in Scheme 3.
First, a Knoevenagel condensation between α-tetralone and
malononitrile gave the malononitrile derivative 5 in 76%
yield.[17] Next, treatment with tropylium tetrafluoroborate
in the presence of Et3N in CH2Cl2 at –78 °C yielded the
VHF precursor 6 in quantitative yield. Its oxidation to
VHF and subsequent ring-closure to DHA were achieved
in a two-step one-pot reaction. Hydride abstraction using
nitrosyl tetrafluoroborate (NOBF4) in MeCN at –40 °C fol-
lowed by the addition of pyridine in CH2Cl2 gave the VHF,
which then immediately converted into the DHN-DHA 3a.
All other attempts to perform this step by using oxidants
such as DDQ (with or without pTsOH), m- or p-chloranil,
or tritylium tetrafluoroborate/Et3N proved fruitless, giving
no reaction or leading to complete decomposition. Also,
the previously reported procedure,[14a] in which two cyclo-
heptatrienyls were incorporated into the structure with one
of these functions acting as a leaving group (i.e., tropylium)
in the subsequent oxidation step, failed. Thus, although the
intermediate 7 was readily obtainable, it could not be con-
verted into 3a.
Figure 2. Molecular structures of 6 (crystals grown from CHCl3/
heptanes) and 3a (crystals grown from EtOH) with displacement
ellipsoids drawn at the 50% propbability level for non-hydrogen
atoms.
To obtain a reactive handle for metal-catalyzed coupling
reactions, the initial idea was to place an iodo substituent
at the 6-position of the α-tetralone moiety, which corre-
sponds to the “para” position of the DHA 1a (relative to
the DHA). First, the treatment of 6-amino-α-tetralone with
NaNO2 in aqueous HCl followed by the addition of KI
gave 6-iodo-α-tetralone (8)[19] in 71% yield. This ketone 8
was then treated with malononitrile in a Knoevenagel con-
densation but the use of Al2O3 (with or without Et3N) in
CH2Cl2 or 1,2-dichloroethane, AcOH/NH4OAc in toluene
at reflux, or TiCl4/pyridine in CH2Cl2 did not give the de-
sired product 9. Instead 8 was treated, in a Sonogashira
cross-coupling reaction, with TIPS-acetylene to afford 10 in
68% yield. Unfortunately, this ketone did not show signifi-
cant reactivity in
a Knoevenagel condensation with
malononitrile under a variety of conditions, including the
use of either Al2O3 (with or without piperidine) in CH2Cl2
or 1,2-dichloroethane, piperidine in absolute EtOH, or
AcOH/NH4OAc in toluene at reflux, and only traces (Ͻ5%
by NMR) of the desired product 11 could be observed. The
attempted syntheses of 9 and 11 are shown in Scheme 4.
Instead, a different strategy towards inserting a reactive
handle into the DHN-DHA was undertaken, focusing upon
the incorporation of a pseudo-halogen (triflate) into the
photoswitch. Commercially available 6-methoxy-α-tetralone
(12) was treated with malononitrile in a Knoevenagel con-
densation using AcOH/NH4OAc in toluene at reflux, yield-
ing the malononitrile derivative 13[20] in 89% yield
Scheme 3. Synthesis of DHN-DHA 3a; * known reaction.
The structures of the VHF precursor 6 and the final (Scheme 5). This compound was then treated with 48%
DHN-DHA 3a were confirmed by X-ray crystallography, HBr at 120 °C,[21] which unfortunately resulted in an unde-
as shown in Figure 2. As found for parent DHA 1a,[18] the sired retro-Knoevenagel condensation as well as the desired
seven-membered ring of 3a adopts a boat-like structure demethylation, with 6-hydroxy-α-tetralone (14) being iso-
with the C7–C8 double bond out of the plane and with the lated as the major product.[22] In an attempt to avoid this,
phenylene ring forced into planarity.
13 was instead treated with BBr3 in CH2Cl2, but after 48 h
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at room temp., unfortunately only the starting material was
regenerated after work-up. Nevertheless, a good result was
finally obtained when 13 was dissolved in molten pyr-
idinium hydrochloride at 150 °C for 30 h in a sealed con-
tainer to give 15 in 68% yield (no retro-Knoevenagel ob-
served).[23] Alternatively, 15 could also be obtained by first
preparing compound 14 by the treatment of 6-methoxy-α-
tetralone (12) with 48% HBr at reflux overnight. With 14[21]
in hand, Knoevenagel condensation with malononitrile was
effected at reflux in AcOH/HMDS to give the desired com-
pound 15 in 60% yield (the use of AcOH/NH4OAc in
toluene at reflux gave 15 in 22% yield). Conveniently, both
methods could be performed on the gram scale and did
not require chromatography for isolation of the products.
In addition, the structure of 15 was confirmed by X-ray
crystallography (Figure 3).
Scheme 4. Attempted synthesis of halogenated DHN-DHA; *
known reaction.
Figure 3. Molecular structure of 15 (crystals grown from CHCl3)
with displacement ellipsoids drawn at the 50% probability level for
non-hydrogen atoms.
Intermediate 15 was then treated with triflic anhydride
and Et3N (pyridine was unsuccessful) in CH2Cl2 at –78 °C
to yield 16 in 90% yield. Using the previously described
procedure, compound 16 was treated with Et3N in the pres-
ence of tropylium tetrafluoroborate to give the selectively
alkylated VHF precursor 17 in almost quantitative yield
(isolated analytically pure in 73% yield). Oxidation and
subsequent ring-closure was facilitated by the treatment of
17 with NOBF4 in MeCN at –20 °C followed by the ad-
dition of pyridine in MeCN/CH2Cl2 to give 4a in 30% yield
(Scheme 5).
The triflated species 16 and 17 are very sensitive to acid.
Even on a TLC plate or in CDCl3 solution, the triflates
were cleaved, and for this reason TLC plates were pre-
treated with 5% Et3N in CH2Cl2 and CDCl3 with Al2O3.
Although the structures of the DHN-DHAs were easily
1
confirmed by H NMR spectroscopy, the presence of the
triflate moiety was, in all three steps, confirmed by 13C and
19F NMR analyses, which showed a quartet at approxi-
mately 119 ppm, with a JC,F coupling constant of 321 Hz,
and a resonance at approximately –71.5 ppm, respectively.
With the triflate-functionalized DHN-DHA (4a) in
hand, we decided to evaluate whether this functionality was
a suitable means to gaining access to functionalized DHN-
DHAs. As the DHA/VHF system has already been success-
fully exploited in functional devices by using SMe and SAc
Scheme 5. Synthesis of triflate-functionalized DHN-DHA 4a;
* known reaction.
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Dihydroazulene/Vinylheptafulvene Photoswitch
as anchoring groups, it was decided to investigate the absorption spectrophotometry. DHN-DHAs 3a and 4a
possibility of using 4a as a precursor for such compounds both exhibit characteristic DHA absorption spectra, each
(Scheme 6). Gratifyingly, the triflate reacted under relatively with a lowest-energy absorption at approximately 365 nm,
mild conditions in a Suzuki cross-coupling reaction with which is redshifted compared with those of CH-DHA 2a
methylthiophenylboronic acid and also rather easily in a (318 nm in EtOH)[15] and DHA 1a (353 nm in MeCN).[18]
palladium-catalyzed SNAr reaction with KSAc, with the in- This redshift is desirable because lower-energy light for
sertion of a methylthio (18a) and the acetyl-protected thiol photoisomerization should imply higher fatigue resistance.
19a, respectively. The amount of base added in both reac- But irradiation with light corresponding to their absorption
tions was crucial as the corresponding azulenes 20–22 were maxima, in both MeCN and EtOH at 25 °C, led to no
isolated in significant amounts (see the Exp. Sect.). Never- changes in the absorption spectra (for details see the Sup-
theless, the structures of both 18a and 19a were confirmed porting Information), which is explained by an extremely
by X-ray crystallography, as shown in Figure 4.
fast back reaction (VHFǞDHA). However, irradiation in
cyclohexane resulted in the formation of species with short-
lived redshifted absorption bands at 455 and 460 nm, as-
signed to the VHF structures 3b and 4b, respectively. Very
quickly after irradiation, a series of absorption spectra were
acquired and, based on these measurements, half-lives of
0.9 and 0.3 s were estimated for 3b and 4b, respectively (the
rate constants were determined by the decay of the absorp-
tions of VHF). For VHF 3b, this change in half-life corre-
sponds to a dramatic more than 150000-fold decrease com-
pared with that of VHF 1b in cyclohexane.[18] Unfortu-
nately, we do not have a point of reference for VHF 4b. The
UV/Vis absorption spectra resulting from an estimated 12
and 3% light-induced conversion of DHN-DHAs 3a and
4a, respectively, into their corresponding short-lived VHFs,
and their conversion back into DHN-DHAs, including the
kinetic details, are provided in the Supporting Information.
To acquire the absorption spectra of the short-lived
VHFs, UV/Vis absorption spectrophotometry was per-
formed at lower temperatures to retard the back reaction.
Gratifyingly, irradiation (366 nm) of DHN-DHA 3a in
EtOH at –60 °C led to the appearance of an absorption
band at 476 nm as a result of its conversion into VHF 3b
(Figure 5). At this temperature, the VHF isomer was rela-
tively long-lived (t1/2 = 13 min), and full conversion from
DHA into VHF was hence accomplished. Similar values
were obtained from a study of 4a/4b, although the half-life
of 4b was significantly shorter, as expected because elec-
tron-withdrawing groups cause an increase in the rate of
thermally induced ring-closure. The triflate-functionalized
DHN-DHA 4a was not studied in detail as the 4a/4b system
was not stable to multiple cycles of light and “heat” and a
complex mixture was obtained. Five light/heat cycles were
performed on a sample of DHN-DHA 3a (in EtOH) with-
out noticeable photodegradation. Although it is known that
the quantum yield for the DHAǞVHF conversion is tem-
perature dependent[9a] (at lower temperatures the mecha-
nism changes to relaxation by fluorescence instead of ring-
opening), it is roughly estimated that the quantum yield for
the DHN-DHA 3aǞVHF 3b conversion is comparable to
that of 1aǞ1b. The absorption maxima of the DHA and
VHF states are listed in Table 1.
Scheme 6. Insertion of SMe and SAc end-groups by palladium-
catalyzed reactions. RuPhos = 2-dicyclohexylphosphino-2Ј,6Ј-di-
isopropoxybiphenyl; dba = dibenzylideneacetone; xantphos = 4,5-
bis(diphenylphosphanyl)-9,9-dimethylxanthene; Hünig’s base: di-
isopropylethylamine; MW = microwave.
Figure 4. Molecular structures of 18 (crystals grown from CHCl3/
heptanes) and 19 (crystals grown from CHCl3/heptanes) with dis-
placement ellipsoids drawn at the 50% probability level for non-
hydrogen atoms.
After irradiation with light the sample was kept at –60 °C
and the back reaction was monitored by acquiring an ab-
sorption spectrum every minute. By plotting the decay of
Spectroscopy and Kinetics
The four DHN-DHAs 3a, 4a, 18a, and 19a were studied the VHF absorption against time, the rate of ring-closure
in EtOH, MeCN, and/or cyclohexane solutions by UV/Vis was determined (first-order kinetics). The UV/Vis absorp-
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S. L. Broman et al.
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closure of 3b to 3a at 25 °C was estimated by extrapolation
to be 54 s–1 (t1/2 = 0.013 s), which corresponds to a dramatic
approximate 950000-fold increase compared with that of 1b
(k = 5.72ϫ10–5 s–1, t1/2 = 12118 s). This larger rate-en-
hancement in the more polar solvent (EtOH) compared
with that in cyclohexane is related to the presence of a
highly polarized or zwitterionic transition state, which
would be stabilized to a higher degree in a polar solvent.[7c]
Also, the activation energy (Ea) and the pre-exponential
factor (A) were determined from the Arrhenius plot to be
68.2Ϯ0.6 kJ/mol and 4.71ϫ1013 s–1, respectively. Using the
Eyring equation, ΔGTS was calculated to be 63.1Ϯ0.2 kJ/
mol. For DHA/VHFs 18a/b and 19a/b, both the absorption
and kinetics data are very similar to those of 3a/b. With
absorption maxima in EtOH of 388 and 374 nm for 18a
and 19a, respectively, and 482 and 485 nm for 18b and 19b,
respectively, both couples exhibit redshifted absorptions as
expected. Also, the ring-closure for 18b and 19b are slightly
faster than that of 3b, in agreement with our previously
published data,[10] which suggests that both the 4-C6H4SMe
and SAc substituents are mildly electron-withdrawing (rate
of back reaction compared at –60 °C). The kinetic data are
listed in Table 2 and the switching event is depicted for 3a/
3b in Scheme 7.
Figure 5. UV/Vis absorption spectra of DHN-DHA 3a and the cor-
responding VHF 3b in EtOH at –60 °C.
Table 1. Absorption maxima for DHAs 1a–4a and VHFs 1b–4b in
various solvents at 25 °C, unless otherwise stated.
Solvent
λmax [nm] (ε [103 m–1 cm–1])
DHA
VHF
1a/b[a]
EtOH
MeCN
CH
354 (13.9)
353 (17.9)
354 (13.6)
318 (6.3)
365 (18.8)
365 (16.0)
364 (17.2)
366 (19.5)
365 (18.1)
364 (18.1)
388 (18.3)
374 (23.5)
471 (18.2)
470 (34.4)
446 (24.6)
427 (7.9)
476 (11.6)
–
2a/b[b]
3a/b
EtOH[c]
EtOH[c]
MeCN
CH
Table 2. Kinetic data for VHFǞDHA conversions for VHFs 1b,
3b, and 4b in various solvents and at various temperatures.
455[d]
4a/b
EtOH[c]
MeCN
CH
486 (7.76)
–
Solvent
Temp. [°C]
k [s–1]
t1/2 [s]
1b[a]
3b
EtOH
MeCN
CH
EtOH
EtOH
EtOH
EtOH
EtOH
CH
25
25
25
–70
–65
–60
–55
–50
25
5.72ϫ10–5
5.36ϫ10–5
0.495ϫ10–5
0.139ϫ10–3
0.384ϫ10–3
0.911ϫ10–3
2.29ϫ10–3
5.22ϫ10–3
0.7(41)
12118
12932
140030
4991
1806
761
302
133
0.9(35)
0.3(15)
565
460[d]
18a/b
19a/b
EtOH[c]
EtOH[c]
482 (6.82)
485 (8.72)
[a] Ref.[18]. [b] Ref.[15]. [c] Performed at –60 °C. [d] Estimated
max Ϯ5 nm.
λ
tion spectra acquired at intervals of 12 min are shown in
Figure 6, and show the decay of VHF 3b and the reforma-
tion of DHN-DHA 3a.
4b
18b
19b
CH
25
2(.20)
EtOH
EtOH
EtOH
–60
–60
–70
1.23ϫ10–3
2.00ϫ10–3
3.09ϫ10–3
347
2244
[a] Ref.[18]
Scheme 7. Fast light/heat-induced interconversion between DHN-
DHA 3a and VHF 3b; * value estimated by extrapolation.
With molar absorptivities between 11.6ϫ103 and
6.82ϫ103 m–1 cm–1 for the VHFs 3b, 4b, 18b, and 19b, and
a molar absorptivity of 7.9ϫ103 m–1 cm–1 previously re-
ported for 2b,[15] it appears that the absorptions of the s-cis
Figure 6. UV/Vis absorption spectra acquired during the VHF
3bǞDHN-DHA 3a conversion (acquired every half-life) in EtOH
(–60 °C). Inset: Arrhenius plot for the VHF 3bǞDHN-DHA 3a
conversion in EtOH. [k] = s–1.
The rate constants for the back reaction of VHFǞDHA VHFs are significantly lower than those of the s-trans
were determined at various temperatures in ethanol, and VHFs. This is in perfect agreement with the high molar
from an Arrhenius plot (Figure 6, inset) the rate of ring- absorptivity previously found for the cyclopentane-
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Dihydroazulene/Vinylheptafulvene Photoswitch
annulated VHF (ε = 27ϫ103 m–1 cm–1 in acetone), which,
with a half-life of Ͼ6 h in silicone,[12a] is thought to exist in
a less sterically congested VHF conformer in solution.
Thus, it seems reasonable to conclude that the VHFs 3b, 4b,
18b, and 19b exist in their congested s-cis-VHF conformers,
which results in a significantly faster VHFǞDHA ring-
closure.
an ESP-MALDI-FT-ICR spectrometer equipped with a 7 T mag-
net (prior to the experiments, the instrument was calibrated using
NaTFA cluster ions) or a MicrOTOF-QII spectrometer using ESP
(calibrated using formic acid). All NMR spectra were recorded
with a 500-MHz instrument equipped with a (non-inverse) cryo-
probe (500.1300/125.7578 MHz) or, in a few examples, with a 300-
MHz (300.0787 Hz) or 500-MHz (499.9704 MHz) instrument with
1
a penta-probe. All H and 13C chemical shifts are referenced to the
residual solvent peak (CDCl3: δH = 7.26 ppm, δC = 77.16 ppm;
[D6]DMSO: δH = 2.50 ppm, δC = 39.52 ppm). The 19F chemical
shifts are referenced to TFA (δF = –76.55 ppm), which was present
in a lock-tube inside the NMR tube during acquisition. All chemi-
cal shifts are given in ppm to two decimal places (signal widths:
13C: approximately 0.004 ppm, 0.5 Hz; 19F: approximately
0.01 ppm, 3 Hz). In the case of compounds 14 and 15, the free
phenol did move some peaks in 13C NMR depending on the con-
centration and water content. Elemental analyses were performed
at the Department of Chemistry, University of Copenhagen or at
London Metropolitan University.
Conclusions
We have developed a protocol for the synthesis of di-
hydronaphthalene-annulated DHAs. For unknown reasons,
iodo- and ethynyl-substituted α-tetralones were reluctant to
undergo Knoevenagel condensation with malononitrile. We
therefore turned to another synthetic strategy in which ulti-
mately a triflate functionality was incorporated. This
pseudo-halogen enabled further functionalization of the
system by metal-catalyzed cross-coupling reactions, and
suitable derivatives as potential components for molecular
electronics devices were synthesized as proof-of-concept.
These DHN-DHAs were shown by kinetics studies (UV/Vis
absorption spectrophotometry) to have great potential, with
respect to both the forward and backward reactions, for the
development of ultrafast photoswitches. The half-life of the
VHFǞDHA conversion was decreased 150000-fold in
cyclohexane and almost 950000-fold in EtOH!
CCDC-1009627 (for 6), -1009628 (for 3a), -1009626 (for 15),
-1050396 (for 18a), and -1050395 (for 19a) contain the supplemen-
tary crystallographic data for this paper. These data can be ob-
tained free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
Experimental Procedures
5,6-Dihydronaphtho[2,1-a]azulene-12,12(11aH)-dicarbonitrile (3a):
NOBF4 (324 mg, 2.77 mmol) was added (see Note 1 below) to a
stirred solution of 6 (393 mg, 1.38 mmol) in dry acetonitrile
(30 mL) at –40 °C. The resulting yellow or light-brown reaction
mixture was stirred for 30 min, after which it was diluted with cold
dry CH2Cl2 (20 mL) and at –40 °C, a solution of pyridine (0.22 mL,
2.8 mmol) in cold dry CH2Cl2 (10 mL) was added dropwise. The
reaction mixture was stirred for an additional 30 min in which it
turned darker brown. The reaction mixture was poured into water
(50 mL) and the reaction mixture extracted with both CH2Cl2 (3ϫ
20 mL) and water (3ϫ 10 mL). The combined organic and aqueous
extracts were separated and the organic phase washed with water
(3ϫ 25 mL), dried with Na2SO4, filtered, and concentrated in
vacuo. Purification by dry column chromatography (SiO2,
12.6 cm2, 0–60% CHCl3/heptanes, 10% steps, 40 mL fractions)
gave 3a (227 mg, 0.800 mmol, 58%, Note 2) as a bright-yellow so-
lid. Crystals suitable for X-ray crystallography were grown from
EtOH. TLC (60% CH2Cl2/heptanes): Rf = 0.52 (UV254 nm), m.p.
Experimental Section
General Methods: All reactions were performed under nitrogen
(using a gas bubbler) or argon (balloon technique). Coupling reac-
tions using palladium catalysts were performed in a solvent flushed
with argon by allowing the argon to flow through the solvent for
at least 20 min while exposed to ultrasound. All chemicals and sol-
vents were used as received, unless otherwise stated. Acetonitrile
was purified and dried using activated Al2O3. THF and 1,4-dioxane
were purified and dried by distillation from a Na/benzophenone
couple. CDCl3 was purified by passing through activated Al2O3.
TLC was carried out on commercially available precoated plates
(silica 60) with fluorescence indicator. Chromatographic purifica-
tions were performed on silica (SiO2) with a pore size of 60 Å and
1
175–178 °C (EtOH). H NMR (500 MHz, CDCl3): δ = 7.68 (d, J
= 7.6 Hz, 1 H), 7.38–7.33 (m, 1 H), 7.29 (td, J = 7.4, 1.2 Hz, 1 H),
7.25 (dd, J = 7.4, 0.8 Hz, 1 H), 6.62 (dd, J = 11.2, 6.4 Hz, 1 H),
6.50 (dd, J = 11.2, 6.1 Hz, 1 H), 6.32 (app. ddd, J = 10.2, 6.1,
2.2 Hz, 1 H), 6.26 (app. dd, J = 6.4, 1.4 Hz, 1 H), 5.86 (dd, J =
10.2, 3.8 Hz, 1 H), 3.78 (app. dt, J = 3.8, 1.9 Hz, 1 H), 2.99 (t, J =
8.3 Hz, 2 H), 2.67–2.52 (m, 2 H) ppm (Note 3). 13C NMR
(126 MHz, CDCl3): δ = 142.98, 138.63, 136.51, 134.12, 130.97,
129.37, 128.47, 128.42, 127.63, 127.47, 123.32, 119.82, 118.12,
115.18, 112.90, 51.24, 42.72, 27.45, 21.37 ppm (one signal missing
due to overlap). HRMS (ESP+): calcd. for [C20H15N2]+ 283.1230
[MH]+; found 283.1235. C20H14N2 (282.34): calcd. C 85.08, H 5.00,
N 9.92; found C 84.97, H 4.96, N 9.98. Notes: 1) The temperature
was kept at –40 °C (Ϯ5 °C). 2) When the reaction was performed
on an approximately 6 mmol scale, the isolated yield was about
a
particle size of 15–40 μm using the dry-column vacuum
chromatography method, as described previously, and with a par-
ticle size of 40–63 µm for flash column chromatography.[13d,14a,24]
All spectroscopic measurements (including photolysis) were per-
formed in a 1-cm path length quartz cuvette. UV/Vis absorption
spectra were recorded in the range 800–200 nm. Photoswitching
experiments were performed by using a 150 W xenon arc lamp
equipped with a monochromator; the DHA absorption maximum
(lowest-energy absorption) for each individual species was chosen
as the wavelength of irradiation (linewidthϮ2.5 nm). The thermal
back reaction was performed by heating the sample (cuvette) by
using a Peltier unit in the UV/Vis spectrophotometer (temperature
kept at 25Ϯ0.1 °C) or, at a low temperature, in a cryostat (–70 to 50%. 3) A correlation between the signal at δ = 3.78 ppm and the
–50Ϯ0.1 °C). All photoswitching experiments were performed in
non-deoxygenated solvents as it has been shown that this does not
significantly improve stability.[3] Mass spectra were recorded with
signals at δ = 6.26 and 6.32 ppm, with coupling constants of 1.4
and 2.2 Hz, gives a broadening of the apparent doublet of triplets
with an apparent coupling constant of 1.9 Hz.
Eur. J. Org. Chem. 2015, 4119–4130
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4125

S. L. Broman et al.
FULL PAPER
12,12-Dicyano-5,6,11a,12-tetrahydronaphtho[2,1-a]azulen-3-yl Tri-
organic phase was washed with water (2ϫ 250 mL), dried with
fluoromethanesulfonate (4a): NOBF4 (904 mg, 7.74 mmol) was MgSO4, and evaporation of the solvents gave 6 (1.19 g, 4.17 mmol,
added to a stirred solution of 17 (1.67 g, 3.87 mmol; Note 1) in dry
MeCN (160 mL) at –20 °C. The color of the solution changed
slowly from colorless to bright yellow or green. After stirring for
1 h with the temperature maintained below –20 °C (Note 2), cold
dry CH2Cl2 (140 mL) was added. The temperature was again kept
at around –20 °C. A solution of dry pyridine (0.62 mL, 7.7 mmol)
in cold dry CH2Cl2 (20 mL) was added and the resulting dark-
yellow solution was stirred for 1 h. The reaction mixture was then
99%) as a colorless foam that solidified. TLC (60% CH2Cl2/hept-
anes): Rf = 0.42 (UV254 nm), m.p. 102.5–103.7 °C. 1H NMR
(300 MHz, CDCl3): δ = 7.99 (dd, J = 8.0, 0.7 Hz, 1 H), 7.46 (td, J
= 7.6, 1.2 Hz, 1 H), 7.30 (dddt, J = 8.0, 7.6, 1.2, 0.7 Hz, 1 H), 7.21
(br. d, J = 7.6 Hz, 1 H), 6.67–6.57 (m, 2 H), 6.31 (dd, J = 9.5,
5.3 Hz, 1 H), 6.23 (dd, J = 9.4, 5.3 Hz, 1 H), 5.31 (dd, J = 9.5,
6.7 Hz, 1 H), 5.16 (dd, J = 9.4, 6.7 Hz, 1 H), 3.50 (app. t, J =
3.7 Hz, 1/2 H), 3.47 (app. t, J = 3.7 Hz, 1/2 H), 2.90 (d, J = 4.1 Hz,
poured into water (100 mL) and extracted with CH2Cl2 (3ϫ 1 H), 2.88 (d, J = 4.3 Hz, 1 H), 2.39 (app. d, J = 7.8, 4.3 Hz, 1/2
100 mL). The extract was dried with Na2SO4, filtered, and concen-
trated in vacuo. Purification by dry-column vacuum chromatog-
raphy (SiO2, 15–40 μm, 0–50% toluene/heptanes, 10% steps, 50–
H), 2.36 (app. q, J = 4.8, 3.7 Hz, 1/2 H), 2.10–2.00 (m, 2 H) ppm
(Note 2). 13C NMR (126 MHz, CDCl3): δ = 176.95, 140.12, 133.56,
131.53, 130.67, 129.66, 129.19, 128.52, 127.08, 126.90, 122.12,
100% toluene/heptanes, 8.3% steps, 40 mL fractions) gave 4 121.80, 113.94, 113.41, 81.05, 42.22, 39.77, 25.04, 24.59 ppm (one
(500 mg, 1.16 mmol, 30%; Note 3) as a yellow oil, which solidified
under high vacuum. TLC (toluene): Rf = 0.64 (UV254 nm), m.p. 129–
130 °C. 1H NMR (500 MHz, CDCl3): δ = 7.71 (d, J = 8.5 Hz, 1
H), 7.25 (dd, J = 8.5, 2.4 Hz, 1 H), 7.20–7.28 (m, 1 H), 6.63 (dd,
J = 11.2, 6.4 Hz, 1 H), 6.54 (dd, J = 11.2, 6.0 Hz, 1 H), 6.34 (ddd,
signal missing). MS [ESP+]: m/z = 91 [C7H7]+, 285 [MH]+, 307
[MNa]+. HRMS (ESP+): calcd. for [C20H16N2Na]+ 307.1206; found
307.1203 [MNa]+. C20H16N2 (284.35): calcd. C 84.48, H 5.67, N
9.85; found C 84.05, H 5.56, N 9.81. Notes: 1) All the tropylium
tetrafluoroborate dissolved and a clear, almost colorless solution
J = 10.2, 6.0, 2.0 Hz, 1 H), 6.33–6.30 (m, 1 H), 5.84 (dd, J = 10.2, was observed. 2) The signals are reported as observed. Not all spin
3.8 Hz, 1 H), 3.78 (dt, J = 3.8, 2.0 Hz, 1 H), 3.04 (t, J = 8.3 Hz, 2
H), 2.72–2.62 (m, 1 H), 2.67–2.55 (m, 1 H) ppm. 13C NMR
(126 MHz, CDCl3): δ = 149.33, 144.55, 139.31, 137.83, 132.30,
131.75, 130.84, 128.80, 127.83, 121.71, 120.25, 119.83, 119.35,
119.34, 118.86 (q, J = 320.9 Hz), 114.78, 112.56, 51.09, 42.73,
27.56, 21.00 ppm. 19F NMR (282 MHz, CDCl3): δ = –71.52 (s, 3
F) ppm. HRMS (MALDI+ FT-ICR, ditranol): calcd. for
[C21H13F3N2O3SNa]+ 453.04912 [MNa]+; found 453.04964.
C21H13F3N2O3S (430.40): calcd. C 58.60, H 3.04, N 6.51; found C
58.48, H 2.98, N 6.44. Notes: 1) We found that the attempted syn-
thesis of 4 from crude 17 was unsuccessful. 2) Starting material
systems could be paired.
6-Iodo-3,4-dihydronaphthalen-1(2H)-one (8):[19]
A solution of
NaNO2 (2.57 g, 37.2 mmol) in H2O (11 mL) was added over the
course of an hour to a stirred solution of 6-amino-3,4-dihydro-
naphthalen-1(2H)-one (5.00 g, 31.0 mmol) in approx. 15% HCl
(25 mL) at 0 °C. The temperature was monitored and kept below
5 °C. The reaction mixture changed from a light-yellow suspension
to a brown mixture with precipitation. A solution of KI (6.18 g,
37.2 mmol) in H2O (20 mL) was added in portions of 4 mL over
the course of around 10 min while carefully monitoring the evol-
ution of N2 gas and mechanically stirring the reaction mixture by
hand. After the addition, the temperature was allowed to reach
room temp. and the mixture was then stirred for 16 h. A heavy
brown-black precipitate was formed in an otherwise clear yellow
aqueous reaction mixture. The contents of the reaction vessel were
consumed, new spot observed. TLC (toluene): Rf
= 0.64
(UV254 nm). 3) When the reaction was performed on an approxi-
mately. 1 mmol scale, the isolated yield was around 50%.
2-[2,3-Dihydronaphthalen-4(1H)-ylidene]malononitrile (5):[17] Acetic
acid (2.1 g, 2.0 mL, 35 mmol) and NH4OAc (501 mg, 6.5 mmol) extracted with Et2O (3ϫ 100 mL) and CH2Cl2 (3ϫ 100 mL), and
were added to
32.0 mmol) and
a
stirred solution of malononitrile (2.11 g,
3,4-dihydronaphthalen-1(2H)-one (4.09 g,
the combined organic extracts were then washed with a mixture
of saturated aqueous Na2S2O4 (40 mL) and H2O (160 mL). The
formation of emulsions was minimized by the addition of a little
brine, and the organic phase was separated and dried with Na2SO4,
filtered, and concentrated in vacuo. The red residue was dissolved
in CH2Cl2 and concentrated in vacuo onto Celite and purification
by dry-column vacuum chromatography (SiO2 15–40 μm, 0–20%
28.0 mmol) in toluene (20 mL), and the flask was equipped with a
Dean–Stark trap. The reaction mixture was heated at reflux for 4 h
(Note 1), after which it was poured into brine (100 mL). Diethyl
ether (100 mL) was added and the organic layer was separated,
dried with MgSO4, filtered, and concentrated in vacuo. The residue
was recrystallized from ethanol (Note 2), which gave 5 (4.12 g,
EtOAc/heptanes, 2.5% steps, 80 mL fractions) gave 8 (6.01 g,
1
21.2 mmol, 76%) as colorless crystals. TLC (toluene): Rf = 0.50 22.1 mmol, 71%) as a light-red solid. The H NMR spectroscopic
(UV254 nm), m.p. 110.1–111.2 °C (EtOH) [ref.[17] 115.3–117.8 °C data are in accordance with the literature.[19]
(EtOH)]. 1H NMR (500 MHz, CDCl3): δ = 8.21 (dd, J = 8.0,
6-Triisopropylsilylethynyl-α-tetralone (10): CuI (18.8 mg, 98.5 μmol,
2 mol-%), [Pd(PPh3)2Cl2] (173 mg, 246 mmol, 5 mol-%), Et3N
(6.86 mL, 49.3 mmol), and TIPS-acetylene (3.29 mL, 14.8 mmol,
3 equiv.) were added to a stirred solution of 6-iodo-α-tetralone (8;
0.7 Hz, 1 H), 7.50 (td, J = 7.5, 1.2 Hz, 1 H), 7.35 (ddd, J = 8.0,
1.2, 0.7 Hz, 1 H), 7.29 (br. d, J = 7.5 Hz, 1 H), 3.03 (t, J = 6.4 Hz,
2 H), 2.89 (t, J = 6.4 Hz, 2 H), 2.04–1.97 (p, J = 6.4 Hz, 2 H) ppm.
13C NMR (126 MHz, CDCl3): δ = 172.67, 142.15, 133.86, 130.18,
1.34 mg, 4.92 mmol) in argon-flushed THF (50 mL), and the reac-
129.61, 128.11, 127.01, 114.13, 113.54, 79.95, 33.19, 29.86,
tion mixture was stirred overnight. The reaction mixture was
22.29 ppm. Notes: 1) TLC (toluene): Rf = 0.30 (starting material).
poured into water (100 mL), extracted twice with diethyl ether
(100 mL), and the combined organic phases were washed with
water (3ϫ 100 mL), saturated aqueous NH4Cl (100 mL), and brine
2) Colorless crystals were obtained by treatment with activated car-
bon.
2-[2-Cyclohepta-2Ј,4Ј,6Ј-trienyl-2,3-dihydronaphthalen-4(1H)-ylid- (100 mL), after which it was dried with MgSO4, filtered, and con-
ene]malononitrile (6): Et3N (0.64 mL, 4.6 mmol) was added drop-
wise over 1 h to a stirred suspension of finely powdered tropylium
tetrafluoroborate (816 mg, 4.59 mmol) and 5 (810 mg, 4.17 mmol)
in dry CH2Cl2 (50 mL) under argon at –78 °C, and the temperature
was then allowed to rise to room temp. The solution was stirred
for 10 min (Note 1) and aqueous 2 m HCl (25 mL) was added. The
centrated in vacuo. Purification by dry-column vacuum chromatog-
raphy (SiO2, 15–40 μm) gave 10 (1.10 g, 33.7 mmol, 68%) as a
1
brown oil. H NMR (500 MHz, CDCl3): δ = 7.96 (d, J = 8.1 Hz,
1 H), 7.38 (d, J = 8.1 Hz, 1 H), 7.36 (br. s, 1 H), 2.93 (t, J = 6.1 Hz,
2 H), 2.69–2.60 (m, 2 H), 2.13 (dt, J = 12.6, 6.4 Hz, 2 H), 1.13 (s, 21
H) ppm. 13C NMR (126 MHz, CDCl3): δ = 197.71, 144.23, 132.16,
4126
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© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 4119–4130

Dihydroazulene/Vinylheptafulvene Photoswitch
131.94, 130.18, 128.47, 127.08, 106.29, 94.57, 39.10, 29.48, 23.11,
(100 mL), dried with Na2SO4, filtered, and concentrated in vacuo
18.66, 11.28 ppm. GC–MS (EI+): m/z = 326.3 [M·+]. HRMS (ESI+ to give a yellow crystalline solid. Recrystallization from boiling
FT-ICR): calcd. for [C21H31OSi]+ 327.21387 [MH]+; found
327.21381.
EtOH (40 mL) gave 15 (330 mg, 1.57 mmol, 23%) as a bright-yel-
low crystalline solid. The mother liquor was concentrated in vacuo
and the residue recrystallized from boiling EtOH (30 mL) to give
15 (222 mg, 1.06 mmol, 16%) as a bright-yellow crystalline solid.
The mother liquor was concentrated in vacuo and purification by
dry-column vacuum chromatography (SiO2, 15–40 μm, 0–100%
CHCl3/heptanes, 20% steps, 0–11%, EtOAc/CHCl3, 1% steps,
40 mL fractions) gave 15 (420 mg, 2.00 mmol, 29%) as an off-white
solid. Notes: 1) A cylinder-shaped glass container, usually used for
microwave heating, with a super-seal was heated using an alumi-
num mantle. The part of the glass that was over the heating mantle
was from time to time covered in pyridinium hydrochloride because
of sublimation, which was then melted back into the mixture by
using a heat gun. 2) On a larger scale (8 g), the content of the reac-
tion vessel was poured (if necessary with the help from a heat gun)
into a mixture of water (0.5 L) and CH2Cl2 (1.5 L) and stirred over-
night.
2-[6-Methoxy-3,4-dihydronaphthalen-1(2H)-ylidene]malononitrile
(13):[20] Acetic acid (40 mL, 0.70 mol) and NH4OAc (30 g,
39 mmol) were added to a stirred mixture of 6-methoxy-α-tetralone
(12; 17.26 g, 97.95 mmol) and malononitrile (12.80 g, 193.8 mmol)
in toluene (500 mL), and the reaction mixture was heated at reflux
for 8 h (Note 1). The resulting light-brown solution was cooled and
poured into a mixture of water (250 mL) and Et2O (250 mL). The
phases were separated and the organic phase washed with water
(3ϫ 250 mL) and brine (250 mL), dried with MgSO4, filtered, and
concentrated in vacuo. The resulting light-yellow crystalline solid
was recrystallized from boiling 96% EtOH (400 mL), which gave
13 (19.50 g, 86.95 mmol, 89%) as off-white to light-grey needle-
shaped crystals. TLC (CH2Cl2): Rf = 0.59. Note: TLC (CH2Cl2):
Rf = 0.21 (starting material, orange-red by treatment with 2,4-dini-
trophenylhydrazine (DNP). 1H NMR spectroscopic data are in ac-
cordance with literature data.[20]
Method 2.1: While stirring, AcOH (7.0 mL, 0.12 mol, 10 equiv.)
was added slowly to HMDS (2.6 mL, 12 mmol, 1 equiv.). 6-
Hydroxy-α-tetralone (14; 2.02 g, 12.5 mmol) and malononitrile
(1.63 g, 24.7 mmol) were added to the resulting clear, colorless solu-
tion, and the mixture heated near reflux for 8 h (Note 1). The reac-
tion mixture was cooled to room temp., then poured into water
(100 mL), and extracted with CH2Cl2 (3ϫ 100 mL). The combined
organic extracts were washed with saturated aqueous NH4Cl
(100 mL), water (100 mL), and brine (100 mL), dried with Na2SO4,
filtered, and concentrated in vacuo. The resulting dark-yellow solid
residue was recrystallized from boiling toluene (250 mL) to give 15
(1.56 g, 7.41 mmol, 60%) as yellow-to-green needle-shaped crystals.
Note 1) The reaction did not go to completion.
6-Hydroxy-α-tetralone (14)
Method 1: A mixture of 13 (3.516 g, 15.68 mmol) and 48% aqueous
HBr (20 mL, 0.18 mol) was stirred at 120 °C for 8 h. The resulting
dark-yellow solution was poured into water (200 mL) and extracted
with CH2Cl2 (3ϫ 100 mL). The combined organic phases were
washed with water (100 mL) and saturated NaHCO3 (50 mL),
dried with Na2SO4, filtered, and concentrated in vacuo. Purifica-
tion by dry-column vacuum chromatography (SiO2, 15–40 μm, 0–
100% CHCl3/heptanes, 10% steps, 0–13% EtOAc/CHCl3, 1%
steps, 40 mL fractions) gave 14 (1.91 g, 11.8 mmol, 75%) as an off-
white crystalline solid.
Method 2:[21] A mixture of 6-methoxy-α-tetralone (12; 6.01 g,
34.1 mmol) and 48% HBr (21 mL, 0.19 mol) was stirred at 120 °C
for 12 h (Note 1). The resulting black solution was cooled to room
temp. after which water was added and 14 (5.26 g, 32.4 mmol, 95%)
was isolated as a dark-red crystalline solid, which was washed with
plenty of water and dried in a desiccator. The compound was
recrystallized from boiling toluene (80 mL), a black oil was dis-
carded, and 14 (4.79 g, 29.5 mmol, 87%) was collected as an off-
white to bright-red needle-shaped crystals (Note 2). TLC (10%
EtOAc/CHCl3): Rf = 0.22–0.31 (UV254nm and orange by treatment
with anisaldehyde or DNP stain and gentle heating, red with vanil-
lin stain and gentle heating), m.p. 153.7–155.2 °C (toluene). 1H
NMR (500 MHz, CDCl3): δ = 7.99 (d, J = 8.6 Hz, 1 H), 6.76 (dd,
J = 8.6, 2.5 Hz, 1 H), 6.68 (d, J = 2.5 Hz, 1 H), 5.77–5.43 (m, 1
H), 2.90 (t, J = 6.3 Hz, 2 H), 2.62 (app. t, J = 6.3 Hz, 2 H), 2.11
(app. pent, J = 6.3 Hz, 2 H) ppm. 13C NMR (126 MHz, CDCl3): δ
= 198.63, 160.27, 147.60, 130.27, 126.57, 114.58, 114.52, 39.01,
30.09, 23.43 ppm. HRMS (MALDI+ FT-ICR, ditranol): calcd. for
[C10H10O2]+ 163.07536 [MH]+; found 163.07537. C10H10O2
(162.19): calcd. C 74.06, H 6.21; found C 74.00, H 6.03. Notes:
1) TLC (10% EtOAc/CHCl3): Rf = 0.94 (starting material). 2) No
noticeable difference in purity by NMR was observed.
Method 2.2: AcOH (0.65 mL, 11 mmol) was added to a stirred mix-
ture of 6-hydroxy-α-tetralone (14; 1.84 g, 11.3 mmol), malono-
nitrile (2.99 g, 45.3 mmol), and NH4OAc (0.437 mg, 5.67 mmol) in
toluene (75 mL), and the mixture was heated at reflux overnight.
While still hot, the resulting light-brown solution was filtered or
decanted from the dark-red oil, which was formed in the reaction,
and the reaction mixture was cooled slowly to 5 °C to give a grey
precipitate. Recrystallization from boiling toluene (75 mL) gave 15
(532 mg, 2.53 mmol, 22%) as off-white needle-shaped crystals.
Crystals suitable for X-ray crystallography were grown from
CHCl3. TLC (10% EtOAc/CH2Cl2): Rf = 0.45–0.53 (UV254nm, and
yellowǞblack upon treatment with DNP stain), m.p. 210–213 °C,
darkens Ͼ170 °C (ethanol). 1H NMR (500 MHz, CDCl3): δ = 8.25
(d, J = 8.8 Hz, 1 H), 6.80 (dd, J = 8.8, 2.7 Hz, 1 H), 6.74 (br. d, J
= 2.7 Hz, 1 H), 5.78 (br. s, 1 H), 2.99 (dd, J = 6.7, 6.2 Hz, 2 H),
2.83 (t, J = 6.3 Hz, 2 H), 1.96 (dt, J = 12.7, 6.3 Hz, 2 H) ppm. 13C
NMR (126 MHz, CDCl3): δ = 171.58, 160.67, 145.64, 130.81,
123.15, 116.03, 114.92, 114.56, 114.07, 33.30, 30.36, 22.11 ppm
(one signal is missing due to overlap with CDCl3). 1H NMR
(500 MHz, [D6]DMSO): δ = 10.79 (br. s, 1 H), 8.12 (d, J = 8.8 Hz,
1 H), 6.81 (dd, J = 8.8, 2.6 Hz, 1 H), 6.74 (d, J = 2.6 Hz, 1 H),
2.94 (t, J = 6.2 Hz, 2 H), 2.76 (t, J = 6.2 Hz, 2 H), 1.82 (app.
pent, J = 6.2 Hz, 2 H) ppm. 13C NMR (126 MHz, [D6]DMSO): δ
= 172.20, 162.93, 146.16, 130.25, 120.98, 115.57, 115.43, 114.60,
114.32, 73.57, 32.62, 29.49, 21.44 ppm. HRMS (ESP+ FT-ICR):
calcd. for [C13H10N2ONa]+ 233.06853 [MNa]+; found 233.06856.
C13H10N2O (210.24): calcd. C 74.27, H 4.79, N 13.33; found C
74.26, H 4.44, N 13.19.
2-[6-Hydroxy-3,4-dihydronaphthalen-1(2H)-ylidene]malononitrile
(15)
Method 1: In a glass-container suitable for high-pressure reactions,
13 (1.52 g, 6.80 mmol) and pyridine hydrochloride (3.49 g,
30.2 mmol) were mixed and heated to 150 °C for 30 h (sealed vessel,
note 1). While still melted, the content of the vessel was poured
into water (100 mL), which was then extracted with CH2Cl2 (3ϫ
5-(Dicyanomethylene)-5,6,7,8-tetrahydronaphthalen-2-yl Trifluoro-
100 mL, note 2). The combined extracts were washed with water methanesulfonate (16): Et3N (3.43 mL, 24.6 mmol, 2.2 equiv.) fol-
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lowed by triflic anhydride (4.19 mL, 22.4 mmol, 2.0 equiv.) were
added dropwise to a mixture of 15 (2.35 g, 11.2 mmol) and dry
CH2Cl2 (120 mL) at –78 °C (an immediate yellow coloration was
observed that slowly faded). The reaction mixture was stirred for
1 h and the resulting orange-to-red reaction mixture was poured
into water (100 mL) and extracted with CH2Cl2 (3ϫ 150 mL). The
combined organic phases were dried with Na2SO4, filtered, and
concentrated in vacuo. Purification by dry-column vacuum
chromatography (SiO2, 15–40 μm, 0–100% CHCl3/heptanes, 12.5%
steps, then neat CHCl3, 40 mL fractions) gave 16 (3.45 g,
10.1 mmol, 90%) as a colorless oil (Note 1). TLC (CHCl3): Rf =
(methylthio)phenyl]boronic acid (104 mg, 618 µmol, 2 equiv.) and
DHN-DHA 4a (133 mg, 309 μmol) and argon-flushed toluene
(36 mL) and water (4 mL), and the reaction mixture was stirred at
50 °C for 6 h (Note 1). Saturated aqueous NH4Cl (50 mL) was
added to the resulting black-green reaction mixture, which was then
extracted with CH2Cl2 (100 mL). The extract was dried with
MgSO4, filtered, and concentrated in vacuo. Purification by flash
column chromagraphy (SiO2, 40–63 μm, toluene, note 2) gave 18a
(12.5 mg,30.9 μmol,10%)asayellow-to-greensolid,12-cyano-5,6-di-
hydronaphtho[2,1-a]azulen-3-yl trifluoromethanesulfonate (20)
(11.2 mg, 27.8 μmol, 9%) as a greenish blue solid (blue band on
column), and 3-[4-(methylthio)phenyl]-5,6-dihydronaphtho[2,1-a]-
azulene-12-carbonitrile (21; 30.5 mg, 80.8 μmol, 26%) as a green
solid (greenish blue band on column) and, presumably, 5,6-dihy-
dronaphtho[2,1-a]azulene-3,12-dicarbonitrile (22; 24.9 mg,
88.8 μmol, 29%) as a green solid (blue band on column). Crystals
of 18a suitable for X-ray crystallography were grown from CHCl3/
heptanes. Data for 18a: TLC (toluene): Rf = 0.50 (purple by treat-
ment with H2SO4 in EtOH), m.p. 188–190 °C. 1H NMR (500 MHz,
CDCl3): δ = 7.72 (d, J = 8.0 Hz, 1 H), 7.57–7.52 (m, 3 H), 7.46 (s,
1 H), 7.34 (d, J = 7.5 Hz, 2 H), 6.62 (dd, J = 11.2, 6.4 Hz, 1 H),
6.50 (dd, J = 11.2, 6.1 Hz, 1 H), 6.34–6.31 (m, 1 H), 6.27 (d, J =
6.4 Hz, 1 H), 5.86 (dd, J = 10.1, 3.7 Hz, 1 H), 3.81–3.79 (m, 1 H),
3.05 (t, J = 8.2 Hz, 2 H), 2.72–2.64 (m, 1 H), 2.63–2.55 (m, 1 H),
2.54 (s, 3 H) ppm. 13C NMR (126 MHz, CDCl3): δ = 142.79,
141.45, 138.69, 138.59, 137.14, 137.00, 134.02, 130.99, 130.97,
127.71, 127.42, 127.41, 127.00, 126.85, 125.75, 123.79, 119.89,
118.14, 115.21, 112.93, 51.31, 42.75, 27.75, 21.47, 15.90 ppm.
HRMS (MALDI+ FT-ICR ditranol): calcd. for [C27H20N2S]·+
357.10561 [M]·+; found 404.13417. C27H20N2S (404.53): calcd. C
80.17, H 4.98, N 6.92; found C 80.07, H 4.94, N 7.02. Data for 20:
TLC (toluene): Rf = 0.37 (blue-purple), m.p. 167–169 °C. 1H NMR
(500 MHz, CDCl3): δ = 8.58 (dd, J = 9.6, 0.9 Hz, 1 H), 8.55 (d, J
= 8.5 Hz, 1 H), 8.33 (dd, J = 9.6, 0.6 Hz, 1 H), 7.75 (tt, J = 9.6,
1.0 Hz, 1 H), 7.48 (t, J = 9.6 Hz, 1 H), 7.44 (t, J = 9.6 Hz, 1 H),
7.31–7.26 (m, 2 H), 3.26–3.21 (m, 2 H), 3.16–3.11 (m, 2 H) ppm
(Note 3). 13C NMR (126 MHz, CDCl3): δ = 149.83, 146.04, 143.75,
1
0.42. H NMR (500 MHz, CDCl3): δ = 8.30 (d, J = 8.8 Hz, 1 H),
7.26 (dd, J = 8.8, 2.6 Hz, 1 H), 7.23 (d, J = 2.6 Hz, 1 H), 3.05 (dd,
J = 6.9, 6.2 Hz, 2 H), 2.95 (t, J = 6.3 Hz, 2 H), 2.05 (dt, J =
12.8, 6.4 Hz, 2 H) ppm. 13C NMR (126 MHz, CDCl3): δ = 170.28,
152.18, 145.12, 130.40, 130.20, 122.33, 119.98, 118.79 (q, J =
320.8 Hz), 113.47, 112.84, 81.88, 32.84, 29.97, 21.90 ppm. 19F
NMR (282 MHz, CDCl3): δ = –71.55 (s, 3 F) ppm. HRMS
(MALDI+ FT-ICR, ditranol): calcd. for [C14H9F3N2O3SNa]+
365.01782 [MNa]+; found 365.01781. C14H9F3N2O3S (342.29):
calcd. C 49.12, H 2.65, N 8.18; found C 49.23, H 2.53, N 8.06.
Note 1) The neat oil was unstable and changed color to brown over
the course of a few weeks.
6-(Cyclohepta-2,4,6-trienyl)-5-(dicyanomethylene)-5,6,7,8-tetra-
hydronaphthalen-2-yl Trifluoromethanesulfonate (17): Et3N
(0.842 mL, 6.04 mmol) was added dropwise to a stirred mixture of
16 (2.05 g, 5.98 mmol) and finely powdered tropylium tetrafluoro-
borate (1.07 g, 6.04 mmol) in CH2Cl2 (150 mL) at –78 °C over the
course of 1 h. The reaction mixture was stirred at –78 °C for 2 h
and then allowed to slowly rise to room temp. over the course of
6 h. The resulting yellow solution of 17 (Note 1) was poured into
a saturated aqueous NH4Cl solution (50 mL), the phases separated,
and the aqueous layer extracted once with CH2Cl2 (50 mL). The
combined organic layers were washed with saturated aqueous
NH4Cl (50 mL), dried with MgSO4, filtered, and concentrated in
vacuo. The brown residue was purified by dry-column vacuum
chromatography [SiO2, 15–40 μm, 1) 0–75 % toluene/heptanes,
12.5% steps, 40 mL fractions, 2) 75–100% toluene/heptanes, 6.25% 141.75, 139.49, 137.71, 135.98, 135.41, 131.56, 128.02, 127.66,
steps, 40 mL fractions] to give 17 (1.89 g, 4.37 mmol, 73%) as an
almost colorless oil that slowly changes to bright-yellow. TLC
(CHCl3): Rf = 0.52; TLC (toluene): Rf = 0.45. 1H NMR (500 MHz,
CDCl3): δ = 8.09 (d, J = 8.8 Hz, 1 H), 7.23 (dd, J = 8.8, 2.5 Hz, 1
H), 7.15 (d, J = 2.5 Hz, 1 H), 6.65 (dd, J = 9.6, 5.5 Hz, 2 H), 6.34
(dd, J = 9.6, 5.5 Hz, 1 H), 6.26 (dd, J = 9.6, 5.5 Hz, 1 H), 5.31 (dd,
J = 9.5, 6.9 Hz, 1 H), 5.13 (dd, J = 9.5, 6.9 Hz, 1 H), 3.50 (t, J =
3.7 Hz, 1/2 H), 3.48 (t, J = 3.7 Hz, 1/2 H), 2.97–2.92 (m, 2 H),
2.42–2.34 (m, 1 H), 2.05–2.01 (m, 2 H) ppm. 13C NMR (126 MHz,
CDCl3): δ = 174.36, 152.10, 143.30, 131.59, 130.82, 130.67, 129.17,
127.46, 127.27, 122.34, 121.55, 121.26, 119.91, 118.75 (q, J =
320.7 Hz), 113.31, 112.73, 82.84, 41.78, 39.64, 24.93, 24.59 ppm.
19F NMR (282 MHz, CDCl3): δ = –71.61 (s, 3 F) ppm (in the crude
127.28, 126.75, 121.74, 120.33, 118.81 (q, J = 320.8 Hz), 118.30,
90.81, 29.88, 20.79 ppm. HRMS (MALDI+ FT-ICR ditranol):
calcd. for [C20H12F3NO3S]·+ 403.04845 [M]·+; found 403.04859.
C20H12F3NO3S (403.37): calcd. C 59.55, H 3.00, N 3.47, S 7.95;
found C 59.51, H 3.03, N 3.47, S 7.86. Data for 21: An analytically
pure sample obtained by recrystallization from boiling CHCl3/
heptanes gave 21 as a fluffy dark-blue solid. TLC (toluene): Rf =
0.30 (green), m.p. Ͼ260 °C. 1H NMR (500 MHz, CDCl3): δ = 8.55
(d, J = 8.5 Hz, 1 H), 8.54 (d, J = 9.8 Hz, 1 H), 8.29 (d, J = 9.8 Hz,
1 H), 7.68 (t, J = 9.8 Hz, 1 H), 7.63–7.60 (m, 1 H), 7.60 (d, J =
8.6 Hz, 2 H), 7.57 (br. s, 1 H), 7.43 (t, J = 9.8 Hz, 1 H), 7.39 (t, J
= 9.8 Hz, 1 H), 7.36 (d, J = 8.6 Hz, 2 H), 3.27–3.22 (m, 2 H), 3.19–
3.14 (m, 2 H), 2.55 (s, 3 H) ppm. 13C NMR (126 MHz, CDCl3): δ
= 146.34, 145.86, 141.89, 139.67, 138.51, 138.44, 137.62, 137.28,
134.90, 134.49, 130.16, 127.50, 127.34, 127.07, 127.02, 126.97,
126.89, 125.99, 118.72, 90.56, 30.01, 21.28, 15.95 ppm (one signal
missing due to overlap). HRMS (MALDI+ FT-ICR ditranol):
calcd. for [C26H19SNa]+ 400.11304 [MNa]+; found 400.11373.
C26H19NS (377.51): calcd. C 82.72, H 5.07, N 3.71, S 8.49; found
C 82.98, H 5.06, N 3.81, S 8.40. Data for 22: M.p. 241–242 °C
–
mixture, signals of BF4 salts were also observed at δ = –149.58
and –149.64 ppm). HRMS (MALDI+ FT-ICR, ditranol): calcd.
for [C21H16F3N2O3S]+ 433.08282 [MH]+; found 433.08293.
C21H15F3N2O3S (432.42): calcd. C 58.33, H 3.50, N 6.48; found C
58.12, H 3.36, N 6.43.Note 1) The complete conversion from 16 to
1
17 was observed by TLC and 19F and H NMR spectroscopy; the
triethylammonium salt and traces of cycloheptatriene were ob-
served.
1
(CHCl3/heptanes). H NMR (500 MHz, CDCl3): δ = 8.61 (d, J =
9.8 Hz, 1 H), 8.56 (d, J = 8.0 Hz, 1 H), 8.36 (d, J = 9.8 Hz, 1 H),
7.79 (t, J = 9.8 Hz, 1 H), 7.68 (d, J = 8.0 Hz, 1 H), 7.63 (br. s, 1
H), 7.50 (t, J = 9.8 Hz, 1 H), 7.46 (t, J = 9.8 Hz, 1 H), 3.24 (dd, J
= 8.3, 6.2 Hz, 2 H), 3.14 (dd, J = 8.3, 6.2 Hz, 2 H) ppm. 13C NMR
3-[4-(Methylthio)phenyl]-5,6-dihydronaphtho[2,1-a]azulene-
12,12(11aH)-dicarbonitrile (18a): K3PO4 (99.3 mg, 468 μmol,
1.5 equiv.), Pd(OAc)2 (9.1 mg, 41 μmol, 0.13 equiv.), and RuPhos
(29.3 mg, 63 μmol, 0.20 equiv.) were added to a mixture of [4-
4128
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© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 4119–4130

Dihydroazulene/Vinylheptafulvene Photoswitch
(126 MHz, CDCl3): δ = 146.06, 143.20, 140.10, 139.68, 137.77,
136.56, 135.97, 135.38, 132.07, 131.42, 127.82, 127.52, 127.44,
126.55, 118.96, 118.13, 112.56, 91.18, 29.46, 20.78 ppm. IR (neat,
concentration, was prepared in cyclohexane. A UV/Vis absorption
spectrum was acquired (see Figure S47, left, red curve). The set-
tings were then adjusted to quickly scan the region between 200
and 800 nm in less than 1 s. The sample was then exposed to light
at 364 nm for 10 min. As quickly as possible, a series of five UV/
Vis absorption spectra were acquired with an approximate 1 s delay
between them (see Figure S48, left). In the first scan, shortly after
light irradiation, an absorption band appeared at 455 nm (assigned
to VHF 3b) and the original band had disappeared (88% of origi-
nal absorption). After 5 s, the original spectrum had reappeared
and the VHF absorption had disappeared. The decay of the VHF
absorption could be followed at 450, 455, and 460 nm, as shown in
Figure S49, and the rate of the back reaction estimated.
film): ν = 2226 (w, CN), 2194 (w, CN), 1276 (m), 1261 (m), 764
˜
(s), 750 (s) cm–1. HRMS (MALDI+ FT-ICR ditranol): calcd. for
[C20H10N2Na]+ 303.08927 [MNa]+; found 303.08921. No satisfac-
tory elemental analysis was obtained. Notes: 1) TLC (toluene): Rf
= 0.53 (4a, brown by treatment with H2SO4 in EtOH). 2) Alterna-
tively, purification could be accomplished by repeated dry-column
vacuum chromatography [SiO2, 15–40 μm, 1) 0–100 % toluene/
heptanes, 5% steps, 40 mL fractions, 2) 0–100% CHCl3/heptanes,
5% steps, 40 mL fractions]. 3) The signals are reported as observed.
Not all spin systems could be paired.
Photoswitching DHN-DHA 4a:
A sample of 4a (2.54 mg,
S-(12,12-Dicyano-5,6,11a,12-tetrahydronaphtho[2,1-a]azulen-3-yl)
Ethanethioate (19a): DHN-DHA 4a (131 mg, 304 μmol), potassium
thioacetate (69.5 mg, 609 μmol, 2 equiv.), [Pd2dba3] (15.8 mg,
15.2 μmol, 5 mol-%), and Xantphos (17.6 mg, 30.4 μmol, 10 mol-
%) were introduced into a glass container suitable for microwave
heating, and the container was charged with argon. Freshly distilled
argon-flushed 1,4-dioxane (5 mL) was added and the mixture was
further flushed with argon with exposure to ultrasound for 10 min
and then diisopropylethylamine (0.1 mL, 0.6 mmol, 2 equiv.) was
added. The septum was replaced with an unpunctured one and the
reaction mixture heated by using microwaves at 140 °C for 60 min
(ca. 77 W, 3 bar). The contents of the reaction vessel were transfer-
red through the use of CH2Cl2 (50 mL) into water (100 mL) and
the phases were separated. The aqueous layer was extracted twice
with CH2Cl2 (50 mL) and the combined organic layers were dried
with Na2SO4, filtered, and concentrated in vacuo. Purification by
repeated flash column chromatography [SiO2, 40–63 μm, 1) 50%
CH2Cl2/heptanes to neat CH2Cl2, 2) 10–20% EtOAc/heptanes,
note) gave 19a (31.1 mg, 87.8 μmol, 29%) as a fluffy yellow solid.
Crystals suitable for X-ray crystallography were grown from
CHCl3/heptanes. TLC (CHCl3): Rf = 0.61 (purple by treatment
with H2SO4 in EtOH), m.p. 162–163 °C. 1H NMR (500 MHz,
CDCl3): δ = 7.68 (d, J = 8.0 Hz, 1 H), 7.39 (br. d, J = 8.0 Hz, 1
H), 7.31 (br. s, 1 H), 6.62 (dd, J = 11.2, 6.4 Hz, 1 H), 6.52 (dd, J
= 11.2, 6.1 Hz, 1 H), 6.32 (ddd, J = 10.2, 6.1, 2.0 Hz, 1 H), 6.29
(br. d, J = 6.4 Hz, 1 H), 5.84 (dd, J = 10.2, 3.9 Hz, 1 H), 3.78 (dt,
J = 3.8, 2.0 Hz, 1 H), 3.00 (t, J = 8.3 Hz, 2 H), 2.71–2.62 (m, 1 H),
2.62–2.53 (m, 1 H), 2.45 (s, 3 H) ppm. 13C NMR (126 MHz,
CDCl3): δ = 193.73, 144.34, 138.25, 137.25, 134.18, 133.37, 133.27,
131.43, 130.90, 129.49, 128.90, 127.72, 123.74, 119.93, 118.89,
114.97, 112.71, 51.20, 42.68, 30.47, 27.35, 21.28 ppm. HRMS
(MALDI+ FT-ICR ditranol): calcd. for [C22H17N2OS]+ 357.10561
[MH]+; found 357.10556. Note: Alternatively, purification can be
accomplished by repeated dry-column vacuum chromatography
[SiO2, 15–40 μm, 1) 0–100% toluene/heptanes, 10% steps, followed
by neat toluene, 40 mL fractions, 2) 0–100% CHCl3/heptanes, 10%
steps, followed by neat CHCl3, 40 mL fractions, 3) 0–40% EtOAc/
heptanes, 2.5% steps, 40 mL fractions].
0.00590 mmol) was dissolved in MeCN (10.0 mL). From this stock
solution, a sample of 0.050 mL was further diluted with MeCN
(2.60 mL). A UV/Vis absorption spectrum was acquired (see Fig-
ure S46, left, black curve) by using the following settings: window:
200–800 nm, interval: 1 nm, scan rate: 600 nm/min. The settings
were then adjusted to quickly scan the region between 200–800 nm
in less than 1 s (window: 200–800 nm, interval: 5 nm, scan rate:
48000 nm/min). The sample was then exposed to light at 364 nm
(a sample of DHA 1a with the same concentration took less than
1 min to fully convert to VHF 1b). No change in the absorption
spectrum was observed after 1 min of irradiation, but conversion
into an unknown species was observed after prolonged irradiation
(see Figure S46, right, red). A new sample, with the same concen-
tration, was prepared in cyclohexane. A UV/Vis absorption spec-
trum was acquired (see Figure S47, left, black curve). The settings
were then adjusted to quickly scan the region between 200 and
800 nm in less than 1 s. The sample was then exposed to light at
364 nm for 10 min. As quickly as possible, a series of three UV/Vis
absorption spectra were acquired with an approximate 1 s delay
between them (see Figure S48, right). In the first scan, shortly after
light irradiation, an absorption band appeared at 460 nm (assigned
to VHF 4b) and the original band had disappeared (97% of origi-
nal absorption). After 5 s, the original spectrum reappeared and
the VHF absorption had disappeared. The decay of the VHF ab-
sorption could be followed at 455, 460, and 465 nm, as shown in
Figure S50, and the rate of the back reaction estimated.
Low-Temperature Photoswitching of DHN-DHA 3a: Using a cryo-
stat placed inside a UV/Vis spectrophotometer, absolute EtOH in
a cuvette was cooled to –40, –50, –60, and –70 °C and baseline
spectra were acquired. From a stock solution of 3a (3.86ϫ10–4 m)
in MeCN, a sample of 0.200 mL was taken and the solvent blown
off by using a stream of nitrogen gas. The solid sample was dis-
solved in absolute EtOH and cooled to, for example, –70 °C. The
settings were then adjusted to quickly scan the region between 200
and 800 nm in less than 5 s (window: 200–800 nm, interval: 2 nm,
scan rate 2400 nm/min). The sample (inside the cryostat) was then
exposed to UV light (366 nm) for 3–5 min and the conversion from
DHA to VHF was monitored. When fully converted, the back reac-
tion was monitored by acquiring a UV/Vis absorption spectrum
every minute until the DHN-DHA was fully reformed. The decay
of VHF was followed at 476 nm. This experiment was repeated at
–65, –60, –55, and –50 °C using the same sample.
Photoswitching of DHN-DHA 3a: A sample of 3a (1.09 mg,
0.00386 mmol) was dissolved in MeCN (10.0 mL). From this stock
solution, a sample of 0.100 mL was further diluted with MeCN
(2.60 mL). A UV/Vis absorption spectrum was acquired (see Fig-
ure S46, left, red curve) by using the following settings: window:
200–800 nm, interval: 1 nm, scan rate: 600 nm/min. The settings
were then adjusted to quickly scan the region between 200–800 nm
in less than 1 s (window: 200–800 nm, interval: 5 nm, scan rate:
48000 nm/min). The sample was then exposed to light at 364 nm
for 10 min (a sample of DHA 1a with the same concentration took
less than 1 min to fully convert into VHF 1b). No change in the
absorption spectrum was observed. A new sample, with the same
Acknowledgments
The University of Copenhagen and the German Research Founda-
tion (DFG) (Graduate College GRK 640 “Sensory Photoreceptors
in Natural and Artificial Systems“) are acknowledged for financial
support.
Eur. J. Org. Chem. 2015, 4119–4130
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Received: March 9, 2015
Published Online: May 7, 2015
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