Expanding the Hammett Correlations for the Vinylheptafulvene Ring-Closure Reaction

Article abstract of DOI:10.1002/ejoc.201601435

A selection of 2,3-diarylated photochromic dihydroazulenes (DHAs) was prepared by following two different protocols. The first protocol relies on the synthesis of a 3-bromo-substituted dihydroazulene, which is subjected to a Suzuki cross-coupling reaction

Full text of DOI:10.1002/ejoc.201601435

A Journal of
Accepted Article
Title: Expanding the Hammett Correlations for the Vinylheptafulvene
Ring-Closure Reaction
Authors: Martin Drøhse Kilse, Mia Harring Hansen, Søren Lindbæk
Broman, Kurt V. Mikkelsen, and Mogens Broendsted Nielsen
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201601435
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10.1002/ejoc.201601435
European Journal of Organic Chemistry
FULL PAPER
Expanding the Hammett Correlations for the Vinylheptafulvene
Ring-Closure Reaction
Martin Drøhse Kilde,[a] Mia Harring Hansen,[a] Søren Lindbæk Broman,[a] Kurt V. Mikkelsen,*[a] Mogens
Brøndsted Nielsen*[a]
Abstract:
A
selection
of
2,3-diarylated
photochromic
energy relationships, Hammett correlations,[6] for donor/acceptor
substitution at either the vinyl position (Ar-X; C-2, based on DHA
numbering) or at the seven-membered ring (Ar-Z; C-7).[7]
Interestingly, the slope (ρ) has opposite signs for these
substitution patterns; that is, an electron-withdrawing substituent
enhances the ring-closure when placed at C-2, while it retards
the ring-closure when placed in the seven-membered ring at C-7,
which was also found in a calculational study by Shahzad et al.[8]
Incorporation of a phenyl group at the exocyclic carbon of VHF
(Y = H; C-3) is known to lead to a remarkable enhancement of
the rate of the ring-closure reaction,[9] but the exact influence of
donor/acceptor substitution has not yet been established at this
position. We therefore decided to investigate the behavior of a
series of compounds with various aryl groups at C-3 and fixed
groups at C-2; i.e., 2,3-disubstituted compounds. Synthetically,
dihydroazulenes (DHAs) has been prepared using two different
protocols. The first protocol relies on the synthesis of a 3-bromo-
substituted dihydroazulene, which in a final step is subjected to a
Suzuki cross-coupling reaction. In the second protocol the two aryl
substituents are introduced early in the synthesis. The DHAs are
photoactive and undergo light-induced ring-opening reactions to
form vinylheptafulvene (VHF) isomers. These VHFs quickly return at
room temperature to DHAs in thermal ring-closure reactions. The
o
kinetics of these reactions was studied at -20 C for two series for
which the substituent at the C-2 position (DHA numbering) was kept
constant, in both cases revealing a linear free-energy relationship
(Hammett correlation). The relationships show that an electron-
donating substituent at C-3 (the exocyclic VHF carbon) enhances
the ring-closure reaction – in contrast to its influence when placed at
C-2. In a computational study (density functional theory calculations), functionalization at C-3 was achieved via two different routes.
three different methods were benchmarked against the experimental
results. In all, this work shows for the first time how the VHF to DHA
switching is influenced by donor-acceptor substitution at the
exocyclic heptafulvene carbon.
The first route took advantage of our previously reported
protocol for incorporating a bromo-substituent at C-3 of DHA
with X = H and with no aryl substituent in the seven-membered
ring.[10] In the other procedure, developed by Daub and co-
workers,[9] the substituent at C-3 is incorporated in the beginning
of the synthesis. From six 2,3-diarylated compounds, we could
generate two series of Hammett correlations.
Introduction
Z
Molecular switches that undergo isomerization reactions upon
external stimuli have attracted attention in various fields within
supramolecular chemistry, materials science, molecular
electronics, biotechnology, and solar energy storage.[1] Some
applications require fast conversions between isomers, while
NC
1 CN
2
X
3
others
require
slow.
Therefore,
establishing
how
k
DHA
functionalization of the molecular switch influences the switching
behavior has a prominent role for advancing the various fields.
We have in the past years focused attention on the
VHF
DHA
Hammett correlation:
Y
ln(ksubstituent) = " #substituent + ln(kH)
Z
dihydroazulene/vinylheptafulvene
(DHA/VHF)
!
light
photo/thermoswitch with two cyano groups at C-1 (Scheme 1).[2]
The DHA to VHF conversion is photo-induced, while the back-
reaction from VHF to DHA is thermally stimulated.[3] We have
previously found that this thermal back-reaction (TBR) can be
tuned to occur within seconds[4] to years[5]. Systematic studies
have shown that the ring-closure reaction follows linear free-
X: slope " > 0 (EWG fast)
Z: slope " < 0 (EDG fast)
Y: slope " ?
NC
CN
VHF
X
Y
[a]
Mr. M. D. Kilde, Ms. M. S. Hansen, Dr. S. L. Broman, Prof. Dr. K. V.
Mikkelsen, Prof. Dr. M. B. Nielsen
Scheme 1. Dihydroazulene/vinylheptafulvene (DHA/VHF) photo-/thermoswitch.
The Hammett correlation has been verified for X and Y substituents. Notice
that the slope ρ will differ by a factor of ln(10) if log is used instead of ln in the
equation. EWG = electron-withdrawing group; EDG = electron-donating group.
Department of Chemistry
University of Copenhagen
Universitetsparken 5, DK-2100 Copenhagen Ø, Denmark
E-mail: kmi@chem.ku.dk, mbn@chem.ku.dk
http://chem.ku.dk/research_sections/solarenergy/
Supporting information for this article is given via a link at the end of
the document.
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10.1002/ejoc.201601435
European Journal of Organic Chemistry
FULL PAPER
Results and Discussion
Synthesis
DHAs 1a-c (X = NO2, H, OMe; Scheme 2) were synthesized by
our previously reported procedures.[11] These compounds were
then subjected to
a
ring-opening-bromination-ring-closure
procedure.[10] This procedure proved to be tolerant towards both
an electron-withdrawing group (EWG), NO2, and an electron-
donating group (EDG), OMe, at position C-2. Thus, treatment of
1a-c with AlCl3 in CH2Cl2 at rt resulted in ring-opening, furnishing
VHFs 2a-c as intermediates after quenching with water. These
were subsequently subjected to a radical bromination reaction
with N-bromosuccinimide (NBS), benzoyl peroxide, and light in
benzene as solvent. In a subsequent ring-closure reaction, the
corresponding 3-bromo-substituted DHAs 3a-c were achieved in
excellent yields (Scheme 2). In the case of the formation of 3a
(X = NO2) and 3b (X = H), the reaction could be followed by the
naked eye by a visible color change from red to yellow. DHAs
3a-c were isolated as yellow solids of various stabilities.
Compound 3c had to be purified by flash column
chromatography and decomposed within a couple of days on the
shelf at rt in the dark. Therefore it had to be stored cold (-18 °C)
or used shortly after purification. Nevertheless, it was possible to
Figure 1. Molecular structure of 3c (crystals grown from CH2Cl2/heptane) with
displacement ellipsoids at 50% probability for non-H atoms (CCDC 1509120).
Isolation of the VHFs 2a-c was possible by addition of ice-cold
heptane to the cold solution of VHFs in CH2Cl2 followed by
removal of the CH2Cl2 by rotary evaporation to give a precipitate
in the cold heptane. This precipitate was filtered to yield the
VHFs in yields of 66% (2a), 67% (2b), and 54% (2c).
Next, we wanted to investigate the possibility for using the
two new bromides 3a and 3c and the known 3b as precursors
for incorporating aryl groups at C-3 of DHA. Previously, we
found 3b to be unreactive in Sonogashira and Suzuki cross-
coupling reactions.[10] Nevertheless, using a catalytic system
consisting of Brettphos/Pd(OAc)2 and heating overnight, we
managed partly to perform Suzuki cross-couplings between 3a-c
and phenylboronic acid or p-methoxyphenylboronic acid. The
reactions gave in some cases the desired DHAs, albeit in low
yields, while in others mainly azulene products. The product
outcomes are summarized in Scheme 3, Figure 2, and Table 1.
Isolation of the arylated DHAs required tedious purification by
repeated chromatography due to incompletion of the reaction
and significant amounts of different by-products, including the
fully unsaturated azulenes shown in Figure 2. A coupling
between 3c and p-nitrophenylboronic acid was also attempted,
but only azulene products were formed.
grow
a
crystal suitable for X-ray crystallography from
CH2Cl2/heptane confirming the position of the bromine (Figure 1).
Compound 3b colorized upon standing on the shelf at rt in the
dark, but was still usable without any observed impurities. On
the other hand, compound 3a could be purified by dry column
vacuum chromatography and seemed bench stable when kept in
the dark at rt for at least a period of one year.
NC
CN
NC
1) AlCl3,
CH2Cl2
CN
Y
X
2) H2O, 0 oC
2a-c
X
NC
(HO)2B
Pd(OAc)2
CN
1a-c
X = NO2: a
X = H: b
X
NBS, (PhCO2)2 PhH, light
BrettPhos, K3PO4
3a-c
X = OMe: c
PhMe/H2O, !
NC
NC
CN
CN
X
Y
X = NO2
H
OMe
(3 steps)
Br
Y = H
4a 4b 4c
5a 5b 5c
Br
X
Y = OMe
3a (78%), 3b (72%), 3c (84%)
Scheme 2. Synthesis of 3-bromo-substituted DHAs. NBS
=
N-
bromosuccinimide.
Scheme 3. Suzuki cross-couplings. BrettPhos = 2-(dicyclohexylphosphino)-
3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl. For yields, see Table 1.
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10.1002/ejoc.201601435
European Journal of Organic Chemistry
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CN
In order to obtain the two 3-(p-nitrophenyl)-substituted
DHA derivatives 11b (X = H) and 11c (X = OMe), we turned to
the original protocol developed for 4b, where the substituent is
included early in the synthesis.[9] The two DHAs were prepared
in six steps starting from p-nitrophenylacetic acid 12 (Scheme 5),
which was converted to the corresponding acid chloride 13 with
SOCl2 in refluxing chloroform. Friedel-Crafts acylations of this
intermediate with benzene and anisole gave the ketones 14b
and 14c, respectively. Next, Knoevenagel condensation
between these products and malononitrile in refluxing toluene
was performed to provide products 15b and 15c, respectively.
From these compounds, the corresponding cycloheptatriene
derivatives, 16b and 16c, were formed by treatment with
tropylium tetrafluoroborate and triethylamine in CH2Cl2 at -78 °C.
The products were then oxidized by treatment with nitrosonium
tetrafluoroborate at -40 °C followed by pyridine to give the VHFs
that when allowed to reach rt spontaneously underwent thermal
cyclization to form the DHAs 11b and 11c. This last step went in
rather poor yield for both compounds, while all the preceding
steps went in good to high yields. The known[9] DHA 4b was
prepared according to the same method.
X
X = NO2
H
OMe
Y = H
6a 6b 6c
7a 7b 7c
Y = OMe
Y
CN
8b (X = H)
8c (X = OMe)
X
CN
Figure 2. Azulene by-products; for yields, see Table 1.
Table 1. Product yields of Suzuki cross-couplings[a] (see Scheme 4 and
Figure 2).
Entry
X
Y
Temp. [οC]
Products (Yields)
4a[b], 6a (traces)
6a (17%)
O
O
1
2
3
4
5
6
7
NO2
NO2
NO2
H
H
75
SOCl2
OH
Cl
85[c]- 95
75
CHCl3, reflux
H
O2N
O2N
12
13
OMe
OMe
OMe
H
5a (4%), 7a[b]
PhX, AlCl3 CS2, 0 oC to rt
O
5b (4%), 7b[b]
CN
CN
65
CH2(CN)2
H
80
7b (27%), 8b (traces)
4c (3%), 6c (13%), 8c (6%)
5c (4%), 7c[b]
NH4OAc/AcOH
O2N
O2N
OMe
OMe
65[c]
65
PhMe, reflux
OMe
X
X
14b (X = H; 91%)
14c (X = OMe; 67%)
15b (X = H; 70%)
15c (X = OMe; 65%)
[a] In general, all reactions were performed overnight. [b] Not isolated, but
judged present according to TLC analysis. [c] Reaction did not go to
completion.
Et3N
BF4
CH2Cl2, -78 oC
To put the reluctance of 3-bromo-substituted DHAs to
undergo Suzuki cross-couplings, in combination with
degradation, under the reaction conditions into perspective, we
subjected the known[11] azulene derivative 9 to a coupling with p-
methoxyphenylboronic acid, which furnished the azulene 10 in
almost quantitative yield (Scheme 4). Thus, the Suzuki cross-
coupling works very well for simple azulene substrates. The
molecular structures of azulenes 6a, 6c, 8c, and 10 were
confirmed by X-ray crystallographic analysis (see SI).
NC
CN
NC
CN
X
1) NOBF4
MeCN, -40 oC
X
2) Pyridine
CH2Cl2
-40 oC to rt...
NO2
NO2
16b (X = H; 93%)
16c (X = OMe; 82%)
11b (X = H; 17%)
11c (X = OMe; 6%)
OMe
(HO)2B
Scheme 5. Synthesis of 2,3-diarylated DHAs.
CN
20 mol% Pd(OAc)2
Me
40 mol% BrettPhos
2 equiv. K3PO4
CN
Br
Optical Properties and Switching Studies
Me
The DHAs were subjected to UV-Vis absorption studies in EtOH.
Representative spectra are shown in Figure 3 and the longest-
wavelength absorption maxima are listed in Table 2. For DHA 5a
(X = NO2), photoisomerization did not occur with isosbestic
points, and we have therefore limited detailed studies to the X =
H and OMe derivatives (see Scheme 6). Thus, these DHAs were
all photoactive, undergoing light-induced conversion to VHFs
PhMe/H2O (9:1), 90 o
94%
C
9
10
OMe
Scheme 4. Suzuki cross-coupling of 3-bromo-substituted azulene derivative.
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10.1002/ejoc.201601435
European Journal of Organic Chemistry
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upon irradiation at 365 nm. Yet, as the back-reaction was very
fast for all of them at rt, the VHF to DHA first-order kinetics had
to be studied at low temperature (-20 oC) in EtOH. The
absorption maxima of the different VHFs and the rate constants
(k) for the ring-closure reactions are listed in Table 2. All the
conversions occurred with isosbestic points in the absorption
spectra. The molecules can be categorized in two classes, each
containing three compounds with either X = H or X = OMe.
Figure 4 shows a plot of ln(k) against the Hammet σY-values for
each of these series (with Y = OMe, H, NO2). A linear correlation
is observed in each case with a negative slope. Thus, we see
clearly that an EDG at C-3 enhances the ring-closure, while the
opposite is true for an EWG.
0.8
DHA
0.6
0.4
0.2
VHF
500
200
300
400
600
700
800
Wavelength (nm)
Figure 3. UV-Vis absorption spectra recorded in EtOH at -20 °C of 4c and its
corresponding VHF.
Figure 4. Hammett correlations for thermally induced ring-closure (VHF →
DHA) substituted at C-3 at -20 οC in EtOH. Top) X = H; Correlation based on
4b, 5b, and 11b. Bottom) X = OMe; Correlation based on 4c, 5c, and 11c.
Estimated error bars are included.
NC
NC
CN
CN
X
k
X =
H
OMe
X
Y = H
4b 4c
Computational Study
To add further support for the substituent dependency on the
thermal back-reactions, we subjected the two series of
Y = OMe 5b 5c
Y = NO2 11b 11c
VHF
Y
DHA
Y
compounds to
a computational study. Calculations were
Scheme 6. The rate constants (k) for the TBRs were determined for the series
performed using Density Functional Theory (DFT) and the
Gaussian 09 program package.[12] Solvent effects were taken
into account using a polarizable continuum model with the
integral equation formalism variant (IEFPCM).[13] All calculations
were done using EtOH as solvent. Three exchange-correlation
X = H and X = OMe.
Table 2. Absorption maxima and VHF-to-DHA kinetics data (-20 oC) for the
DHAs 4b, 5b, 11b, 4c, 5c and 11c and their corresponding VHFs in EtOH.
functionals (CAM-B3LYP,[14] M06-2X,[15] and PBE0[16]
)
in
DHA
label
DHA λmax
(nm)
VHF λmax
(nm)
t1/2
(min)
X
Y
ο
k-20 C (s-1)
conjunction with the 6-311+G(d) basis set were applied, since
earlier studies[17] have shown adequate performance over a
range of solvents for similar molecular structures. Only the R
enantiomers of the DHAs were taken into account. The
381
332
349
327
361
360
346
5a
4b
NO2
H
OMe
H
316, 493
314, 510
415, 490
347, 488
340, 498
365, 485
47.0 x 10-5
57.5 x 10-5
27.1 x 10-5
14.7 x 10-5
18.8 x 10-5
9.94 x 10-5
25
20
o
temperature was set to -20 C (253.15 K) corresponding to the
5b
H
OMe
NO2
H
experimental conditions. All the calculated transition states (TSs)
were confirmed as first order saddle points by one single
imaginary frequency. All optimized structures (DHA, s-cis/s-trans
VHF, and TS structures) and Gibbs free energies are included in
the SI. The thermal back-reaction (TBR) barrier is determined as
the energy difference between the s-cis-VHF and the TS
structure. These Gibbs free energies of activation are shown in
Figure 5 for the two series of compounds. First of all, we note
that the barriers are significantly lower than that previously
43
11b
4c
H
79
OMe
OMe
OMe
61
5c
OMe
NO2
116
11c
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10.1002/ejoc.201601435
European Journal of Organic Chemistry
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obtained for the VHF of the parent system 1b (ca. 100 kJ mol-
OMe
NO2
H
8.71
4.59
6.23
3.70
4.52
0.40
1.72
2.26
2.19
1.64
1.11
0.71
1.71
0.86
0.85
H
1
[17]
)
, which is in line with the ultrafast TBRs observed
H
experimentally. The differences in barriers are quite small
between individual compounds in both series, but we do find the
same trends as observed experimentally. Thus, for all methods
(except for M06-2X with X = OMe), the barrier height increases
when going from an EDG (OMe) to an EWG (NO2) on position Y.
Now, for a direct comparison to experiment, we need to consider
also the s-trans/s-cis pre-equilibrium since its equilibrium
constant K may differ for the various substitution patterns. These
equilibrium constants are listed in Table 3. From the Eyring
equation, the Gibbs free energies of activation were converted to
rate constants, and these were then multiplied by K / (K+1). The
ratios between these rate constants are plotted in Figure 6.
Again, the CAM-B3LYP and PBE0 functionals give the same
relative rates as observed experimentally, while the results from
the M06-2X functional deviate from the experiments.
OMe
OMe
OMe
OMe
NO2
Figure 6. Calculated ratios between rate constants (kY/kH) for the VHF → DHA
conversion in EtOH at -20 oC taking the s-trans/s-cis pre-equilibrium constant
K into account; each rate constant obtained from the Gibbs free energy
difference between s-cis-VHF and the TS structure was multiplied by K / (K+1).
Top) X = H; compounds 4b, 5b, and 11b. Bottom) X = OMe; Compounds 4c,
5c, and 11c.
Conclusions
Figure 5. Calculated Gibbs free energies of activation for the s-cis-VHF →
DHA conversion in EtOH at -20 oC. Top) X = H; compounds 4b, 5b, and 11b.
Bottom) X = OMe; Compounds 4c, 5c, and 11c.
We have employed two synthetic protocols for achieving a
selection of 2,3-diarylated DHAs. The one protocol relied on
ready access to 3-bromo-substituted DHAs, but suffered from
rather poor yields from the subsequent Suzuki cross-couplings.
In the other protocol both aryl groups were incorporated early in
the synthesis. The individual steps here proceeded in high yields,
except, however, for the final oxidation step to generate
VHF/DHA. In total, we have managed to prepare six new 2,3-
diarylated DHAs. The ring-closure kinetics of the corresponding
VHFs of five of these compounds together with the VHF formed
from the known 2,3-diphenyl-substituted DHA was studied at low
Table 3. Calculated equilibrium constants for the s-trans-VHF ⇔ s-cis-
VHF equilibria at -20 oC (going from s-trans-VHF to s-cis-VHF) based on
three different functionals.
X
Y
CAM-B3LYP
M06-2X
PBE0
H
6.61
0.82
1.18
H
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10.1002/ejoc.201601435
European Journal of Organic Chemistry
FULL PAPER
to afford the title compound (134 mg, 0.445 mmol, 66%) as a metallic
blue powder (Note 2). 1H NMR (500 MHz, CDCl3) δ 8.35 (d, J = 8.8 Hz,
2H), 7.60 (d, J = 8.8 Hz, 2H), 6.81–6.75 (m, 1H), 6.54–6.47 (m, 2H),
6.43–6.35 (m, 2H), 6.01 (dd, J = 12.1, 7.9 Hz, 1H), 5.82 (dd, J = 12.1, 2.3
Hz, 1H) ppm. 13C NMR (126 MHz, CDCl3) δ 165.87, 154.43, 149.23,
142.68, 141.64, 136.67, 135.71, 135.57, 135.09, 134.97, 129.66, 125.06,
118.29, 114.57, 114.01, 77.57 ppm. Elem. anal. calc. for C18H11N3O2
(301.09): C: 79.75%, H: 4.82%, N: 9.71%, found: C: 57.02%, H: 2.70%,
N: 10.93%. Note 1) If further starting material was present, more AlCl3
was added. Note 2) The compound turns back to 1a in crystalline form
within an hour at rt and was thus stored cold at -18 °C.
temperature. The compounds can be categorized in two classes
where the substituent at the VHF vinyl position (C-2 of DHA) is
the same, while the substituent at the exocyclic VHF carbon (C-
3 of DHA) is varied. For each of these classes a Hammett
correlation was obtained, characterized by a negative slope.
This result implies that electron-donating groups at C-3 enhance
the ring-closure reaction. The influence of a substituent at this
position is hence opposite to that previously established for a
substituent at C-2. The experimental results were supported by
DFT calculations when using the CAM-B3LYP and PBE0
functionals, but only partly based on the M06-2X functional. In all,
this is the first systematic study revealing how the VHF ring-
closure reaction is influenced by donor-acceptor substitution at
position C-3 of DHA, which is important in the design of fast or
slow molecular switches for various applications.
2-(2-(2,4,6-Cycloheptatriene-1-ylidene)-1-
phenylethylidene)malononitrile (2b). To a stirred solution of 1b (262
mg, 1.02 mmol) in CH2Cl2 (35 mL) at rt was added AlCl3 (412 mg, 3.09
mmol). After continued stirring for approximately 20 min (complete ring-
opening to the VHF was furnished as judged by TLC (Note 1)), the
mixture was cooled using an ice-bath and quenched by addition of ice-
cold water (100 mL) after which the phases were separated. The
aqueous phase was extracted with ice-cold CH2Cl2 (3 x 50 mL) and the
combined organic phases were dried with MgSO4 and filtered. To the
cold CH2Cl2 solution, heptane (100 mL) was added, and then the CH2Cl2
was removed upon concentration in vacuo. The resulting precipitate was
collected by suction filtration and washed with ice-cold heptane (50 mL)
to afford the title compound (175 mg, 0.682 mmol, 67%) as a metallic
green powder (Note 2). 1H NMR (500 MHz, CDCl3) δ 7.54 – 7.44 (m, 3H),
7.41 – 7.35 (m, 2H), 6.74 – 6.65 (m, 1H), 6.42 – 6.35 (m, 2H), 6.33 (s,
1H), 6.30 – 6.24 (m, 1H), 5.92 – 5.81 (m, 2H).13C NMR (126 MHz,
CDCl3) δ 169.10, 154.09, 142.53, 135.66, 135.30, 135.21, 135.18,
134.59, 133.71, 131.20, 129.87, 128.26, 119.16, 115.19, 114.71; one
signal missing. Note 1) If further starting material is present, more AlCl3 is
added. Note 2) The compound turns back to 1b in crystalline form within
an hour at rt and was thus stored cold at -18 °C.
Experimental Section
General Methods. All handling of photochromic compounds was done in
the dark. All operations involving photochromic DHAs (evaporation of
solvents, column chromatography, and reactions) were done in
glassware wrapped in aluminum foil. All reactions were done under
nitrogen (using
a gas bubbler) or argon (balloon technique). All
palladium-catalyzed Suzuki couplings were performed in solvents flushed
with argon (on an ultrasound bath, letting argon flow through the solvent
for at least 10 min). All chemicals and solvents were obtained from
commercial suppliers and used as received unless otherwise stated.
CDCl3 was passed through activated Al2O3 before use. Thin-layer
chromatography (TLC) was carried out in the dark on commercially
available precoated plates (silica 60) with fluorescence indicator; color
change from yellow to red upon irradiation with UV light (365 nm, not 254
nm) indicated the presence of a DHA. All melting points are uncorrected.
All spectroscopic measurements were performed in a 1-cm path length
cuvette using a cryostat, placed inside a UV-Vis spectrophotometer,
which kept the temperature at -20 οC. UV−Vis absorption spectra were
obtained by scanning the wavelengths from 800 to 200 nm. Absorption
data for the VHF were obtained after light-induced ring opening of the
corresponding DHA using a UV lamp (365 nm). The thermal back-
reaction was followed by heating the sample (cuvette) by the cryostat unit
in the UV-Vis spectrophotometer. NMR spectra were acquired on 300
MHz, 400 MHz, or 500 MHz instruments. All chemical shift values in 1H
and 13C NMR spectra are referenced to the residual solvent peak (CDCl3
δH = 7.26 ppm and δC = 77.16 ppm). All processing of the NMR spectra,
calculation of coupling constants, peak-picking, and so forth were done
without exponential apodization (line broadening), but NMR spectra
presented in the SI are shown with exponential apodization equal to 0.3
Hz for 1H and 1.0 Hz for 13C.
2-(2-(2,4,6-Cycloheptatriene-1-ylidene)-1-(4’-methoxy-
phenyl)ethylidene)malononitrile (2c). To a stirred solution of 1c (162
mg, 0.566 mml) in CH2Cl2 (30 mL) at rt was added AlCl3 (220 mg, 1.65
mmol). After continued stirring for approximately 20 min (complete ring-
opening to the VHF was furnished as judged by TLC (Note 1)), the
mixture was cooled using an ice-bath and quenched by addition of ice-
cold water (100 mL) after which the phases were separated. The
aqueous phase was extracted with ice-cold CH2Cl2 (3 x 50 mL) and the
combined organic phases were dried with MgSO4 and filtered. To the
cold CH2Cl2 solution, heptane (100 mL) was added and then the CH2Cl2
was removed upon concentration in vacuo. The resulting precipitate was
collected by suction filtration and washed with ice-cold heptane (50 mL)
to afford the title compound (136 mg, 0.475 mmol, 84%) as a metallic
green powder (Note 2). Note 1) If further starting material is present,
more AlCl3 is added. Note 2) The compound turns back to 1c in
crystalline form within an hour at rt, and was thus stored cold at -18 °C.
1H NMR (500 MHz, CDCl3) δ 7.38 (d, J = 8.9 Hz, 2H), 6.97 (d, J = 8.9 Hz,
2H), 6.69 – 6.63 (m, 1H), 6.35 (dd, J = 9.0, 3.5 Hz, 2H), 6.27 (s, 1H),
6.26–6.22 (m, 1H), 5.95–5.88 (m, 2H), 3.87 (s, 3H) ppm. 13C NMR (126
MHz, CDCl3) δ 168.88, 162.32, 154.02, 142.26, 135.41, 135.33, 134.95,
134.18, 133.33, 130.47, 126.96, 119.38, 115.67, 115.17, 115.04, 75.69,
55.60 ppm.
2-(2-(2,4,6-Cycloheptatriene-1-ylidene)-1-(4’-nitro-
phenyl)ethylidene)malononitrile (2a). To a stirred solution of 1a (204
mg, 0.677 mmol) in CH2Cl2 (30 mL) at rt, was added AlCl3 (300 mg, 2.25
mmol). After continued stirring for approximately 20 min (complete ring-
opening to the VHF were furnished as judged by TLC (Note 1)), the
mixture was cooled using an ice-bath and quenched by addition of ice-
cold water (100 mL) after which the phases were separated. The
aqueous phase was extracted with ice-cold CH2Cl2 (3 x 50 mL) and the
combined organic phases were dried with MgSO4 and filtered. To the
cold CH2Cl2 solution heptane (100 mL) was added, and then the CH2Cl2
was removed upon concentration in vacuo. The resulting precipitate was
collected by suction filtration and washed with ice-cold heptane (50 mL)
3-Bromo-2-(4’-nitrophenyl)-1,8a-dihydroazulene-1,1-dicarbonitrile
(3a). To a stirred solution of DHA 1a (507 mg, 1.68 mmol) in CH2Cl2 (50
mL) at rt was added AlCl3 (670 mg, 5.03 mmol) (Note 1). After continued
stirring for approximately 20 min (complete ring-opening to the VHF as
judged by TLC; Note 2), the mixture was cooled using an ice-bath and
quenched by addition of ice-cold water (100 mL). The phases were
separated and the aqueous phase was extracted with CH2Cl2 (4 x 50 mL).
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201601435
European Journal of Organic Chemistry
FULL PAPER
The combined organic phases was dried with MgSO4, filtered and
concentrated in vacuo, while the flask was kept in an ice-bath. The
resulting red residue (Note 3) was then dissolved in benzene (40 mL),
and NBS (800 mg, 4.49 mmol) was added. The solution was stirred for 5
min after which benzoyl peroxide (30 mg, 0.12 mmol) was added. The
solution was irradiated with a 500-W white-light halogen lamp kept at a
distance of ca. 1.5 m from the reaction mixture. After 1.5 h, the solution
had changed color from red to orange-yellow. The organic layer was
quenched with water (100 mL) and washed with brine (100 mL), dried
over Na2SO4, and finally filtered. The solvent was removed in vacuo and
the crude residue was dissolved in CH2Cl2, Celite was added and the
mixture was concentrated in vacuo. Purification by dry column vacuum
chromatography (SiO2, 15–40 µm 12.6 cm2, 0–15% EtOAc/heptanes, 1%
steps, 40 mL fractions) gave the title compound (500 mg, 1.32 mmol,
After continued stirring for approximately 20 min (complete ring-opening
to the VHF as judged by TLC; Note 2), the mixture was cooled using an
ice-bath and quenched by addition of ice-cold water (100 mL). The
phases were separated and the aqueous phase was extracted with
CH2Cl2 (4 x 50 mL). The combined organic phases was dried with
MgSO4, filtered and concentrated in vacuo, while the flask was kept in an
ice-bath. The resulting red residue (Note 3) was then dissolved in
benzene (45 mL), and NBS (620 mg, 3.48 mmol) was added. The
solution was stirred for 5 min after which benzoyl peroxide (15 mg, 0.062
mmol) was added. The solution was irradiated with a 500-W white light
halogen lamp kept at a distance of ca. 1.5 m from the reaction mixture.
The reaction progress was followed by TLC until no sign of VHF
(approximately 3 h). Then the suspension was filtered and the organic
layer was washed with water (100 mL), brine (100 mL), dried over
MgSO4, and finally filtered. Purification by flash column chromatography
(SiO2 40–63 µm, loading: CS2, 10% EtOAc/heptane) gave the title
compound (346 mg, 0.947 mmol, 84%) as yellow crystals that in time
change color to purple. TLC (toluene): Rf = 0.52. 1H NMR (500 MHz,
CDCl3) δ 7.72 (d, J = 8.9 Hz, 2H), 7.03 (d, J = 8.9 Hz, 2H), 6.67 (dd, J =
11.3, 6.4 Hz, 1H), 6.54 (dd, J = 11.3, 6.1 Hz, 1H) 6.51 (dd, J = 6.4, 1.2
Hz, 1H), 6.34 (ddd, J = 10.1, 6.1, 2.0 Hz, 1H), 5.76 (dd, J = 10.1, 3.9 Hz,
1H), 3.88 (s, 3H), 3.75 (dt, J = 3.9, 2.0 Hz, 1H) ppm. 13C NMR (126 MHz,
CDCl3) δ 161.21, 136.31, 136.20, 131.60, 130.50, 130.42, 128.21,
125.56, 123.04, 121.70, 119.65, 114.66, 114.61, 112.30, 55.55, 48.95,
47.33 ppm. HRMS (MALDI+ FT-ICR, ditranol) m/z 363.01340 (100%),
365.01136 (100%) [M-H- 79/81Br], calcd. for (C19H12BrN2O+ 79/81Br) m/z
363.01275 (100.0%), 365.01071 (97.3%). Crystals suitable for X-ray
crystallography were grown from CH2Cl2/heptane.
78%) as yellow crystals. TLC (25% EtOAc/heptanes), Rf
= 0.49,
(toluene): Rf = 0.62. M.p. 113–116 °C. 1H NMR (500 MHz, CDCl3) δ 8.38
(d, J = 8.6, 2H), 7.90 (d, J = 8.6, 2H), 6.75–6.68 (m, 1H), 6.66–6.59 (m,
2H), 6.42–6.36 (m, 1H), 5.81-5.75 (dd, J = 10.3, 3.7 Hz, 1H), 3.80 (br s,
1H) ppm. 13C NMR (126 MHz, CDCl3) δ 148.75, 137.19, 135.13, 133.92,
132.89, 130.31, 130.23, 129.47, 128.51, 124.42, 123.75, 119.67, 113.95,
111.64, 48.90, 47.25 ppm. Elem. anal. calc. for C18H10BrN3O2 (320.20):
C: 56.86%, H: 2.65%, N: 11.05%, found: C: 57.02%, H: 2.70%, N:
10.93%. HRMS (MALDI+ FT-ICR, ditranol) m/z 377.98796 (100%),
+
379.98595 (91.4%) [M-H-], calcd. for (C18H9BrN3O2 79/81Br) m/z
377.98727 (100.0%), 379.98522 (97.3%). Note 1) The solution turned
immediately dark red. Note 2) Red spot is sign of VHF whereas the DHA
is yellow. 3) The residue can instead of red have a metal green color.
3-Bromo-2-phenyl-1,8a-dihydroazulene-1,1-dicarbonitrile (3b). To a
stirred solution of DHA 1b (310 mg, 1.21 mmol) in CH2Cl2 (40 mL) at rt
under an argon atmosphere was added AlCl3 (440 mg, 3.30 mmol) (Note
1). After continued stirring for approximately 20 min (complete ring-
opening to the VHF as judged by TLC; Note 2), the mixture was cooled
using an ice-bath and quenched by addition of ice-cold water (100 mL).
The phases were separated and the aqueous phase was extracted with
CH2Cl2 (4 x 50 mL). The combined organic phases was dried with
MgSO4, filtered and concentrated in vacuo, while the flask was kept in an
ice-bath. The resulting red residue (Note 3) was then dissolved in
benzene (40 mL), and NBS (430 mg, 2.42 mmol) was added. The
solution was stirred for 5 min after which benzoyl peroxide (30 mg, 0.12
mmol) was added. The solution was irradiated with a 500-W white light
halogen lamp kept at a distance of ca. 1.5 m from the reaction mixture.
The reaction progress was monitored by TLC until no sign of VHF. Then,
the suspension was filtered, CH2Cl2 (100 mL) was added and the organic
layer was washed with water (100 mL), brine (100 mL), dried over
MgSO4, and finally filtered. Purification by flash column chromatography
(SiO2 40-63 µm, loading: CS2, 10% EtOAc/heptane) gave the title
compound (290 mg, 0.865 mmol, 72%) as yellow crystals. TLC (toluene):
1,8a-Dihydro-2-(4’-methoxyphenyl)-3-phenylazulene-1,1-
dicarbonitrile (4c). To a stirred solution of 3c (165 mg, 0.457 mmol) in a
mixture of toluene (18 mL) and water (2 mL) were added phenylboronic
acid (135 mg, 1.11 mmol), K3PO4 (165 mg, 0.810 mmol), BrettPhos (112
mg, 0. 24 mmol), and Pd(OAc)2 (23 mg, 0.12 mmol). The reaction
mixture was heated at 65 °C overnight, after which it was quenched with
a saturated aqueous solution of NH4Cl and diluted with CH2Cl2 (100 mL).
The organic layer was washed with a saturated aqueous solution of
NH4Cl (3 × 50 mL), dried with MgSO4, filtered, and the solvents were
removed in vacuo. The residue was subjected to flash column
chromatography (SiO2 40-63 µm, loading: CS2, gradient elution 80−100%
toluene/heptane), which gave 6c (20 mg, 0.060 mmol, 13%) as a blue
bright solid and 8c (8 mg, 0.03 mmol, 6%) as a red solid. Fractions
containing 4c were concentrated in vacuo to give a brown oil with major
impurities. This brown oil of 4c was subjected to flash column
chromatography (SiO2 40-63 µm, loading: CS2, 13% EtOAc/heptane)
which gave 4c (5 mg, 0.01 mmol, 3%) as a yellow solid. 4c: TLC
(toluene): Rf = 0.42, (12.5% EtOAc/heptane): Rf = 0.48. 1H NMR (500
MHz, CDCl3) δ 7.37–7.34 (m, 3H), 7.30 (d, J = 8.9 Hz, 2H), 7.18 (ddd, J =
5.7, 3.0, 1.5 Hz, 2H), 6.79 (d, J = 8.9 Hz, 2H), 6.55 (dd, J = 11.2, 6.2 Hz,
1H), 6.49 (dd, J = 11.2, 5.9 Hz, 1H), 6.34 (ddd, J = 10.0, 5.9, 1.9 Hz, 1H),
6.03 (d, J = 6.2 Hz, 1H), 5.82 (dd, J = 10.0, 4.0 Hz, 1H), 3.78 (s, 3H),
3.73 (dt, J = 4.0, 1.9 Hz, 1H) ppm. 13C NMR (126 MHz, CDCl3) δ 160.29,
144.09, 140.42, 136.02, 133.03, 131.31, 130.54, 130.43, 129.42, 129.04,
128.91, 127.64, 123.93, 120.40, 119.55, 116.02, 114.29, 113.32, 55.39,
50.23, 47.18 ppm. HRMS (ESP+, FT-ICR, TFA added) m/z 358.12023
[M•+], calcd. for (C25H18N2O•+) m/z 358.12024. 6c: TLC (toluene): Rf =
0.17 1H NMR (500 MHz, CDCl3) δ 8.69 (d, J = 9.8 Hz, 1H), 8.38 (d, J =
9.8 Hz, 1H), 7.78 (t, J = 9.8 Hz, 1H), 7.52 (t, J = 9.8 Hz, 1H), 7.50–7.46
(m, 2H), 7.41 (t, J = 9.8 Hz, 1H), 7.38–7.31 (m, 3H), 7.18 (d, J = 8.8 Hz,
2H), 6.94 (d, J = 8.8 Hz, 2H), 3.86 (s, 3H) ppm. 13C NMR (126 MHz,
CDCl3) δ 159.04, 151.07, 144.30, 140.37, 139.67, 137.63, 136.25,
134.27, 132.44, 130.52, 129.62, 128.60, 127.93, 127.50, 127.04, 117.94,
114.24, 96.22, 55.43 ppm; one signal missing due to overlap. HRMS
(MALDI+ FT-ICR, ditranol) m/z 335.13076 [M•+], calcd. for (C24H17NO•+)
1
Rf = 0.72. M.p. 125–127 °C. H NMR (500 MHz, CDCl3) δ 7.72–7.68 (m,
2H), 7.54–7.50 (m, 3H), 6.68 (dd, J = 11.3, 6.4 Hz, 1H), 6.57 (dd, J =
11.3, 6.0 Hz, 1H), 6.54 (dd, J = 6.4, 1.2 Hz, 1H), 6.35 (ddd, J = 10.1, 6.0,
2.0 Hz, 1H), 5.77 (dd, J = 10.1, 3.9 Hz, 1H), 3.77 (dt, J = 3.9, 2.0 Hz, 1H)
ppm. 13C NMR (126 MHz, CDCl3) δ 136.62, 135.94, 131.95, 130.91,
130.54, 130.42, 129.17, 128.91, 128.23, 127.08, 122.21, 119.75, 114.41,
112.04, 48.99, 47.56 ppm. HRMS (MALDI+ FT-ICR, ditranol) m/z
+
333.00251 (100%), 335.00046 (98.9%) [M+], calcd. for (C18H11BrN2
79/81Br) m/z 333.00219 (100%), 335.00024 (97.3%). Note 1) The solution
turned immediately dark red. Note 2) Red spot is sign of VHF whereas
the DHA is yellow. Note 3) The residue can instead of red have a metal
green color.
3-Bromo-2-(4’-methoxyphenyl)-1,8a-dihydroazulene-1,1-
dicarbonitrile (3c). To a stirred solution of 1c (323 mg, 1.13 mmol) in
CH2Cl2 (40 mL) at rt was added AlCl3 (500 mg, 3.79 mmol) (Note 1).
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201601435
European Journal of Organic Chemistry
FULL PAPER
m/z 335.13101. Crystals suitable for X-ray crystallography were grown
from CH2Cl2/heptane. 8c: TLC (toluene): Rf = 0.07 1H NMR (500 MHz,
CDCl3) δ 8.73 (d, J = 9.9 Hz, 2H), 8.08 (d, J = 8.9 Hz, 2H), 8.02 (t, J = 9.9
Hz, 1H), 7.83 (t, J = 9.9 Hz, 2H), 7.13 (d, J = 8.9 Hz, 2H), 3.92 (s, 3H)
ppm. 13C NMR (126 MHz, CDCl3) δ 161.94, 155.24, 145.74, 140.95,
137.32, 131.65, 131.31, 124.29, 116.47, 115.12, 96.33, 55.66 ppm.
HRMS (ESP+, FT-ICR, TFA added) m/z [M+H+] 285.10261, calcd. for
(C19H13N2O+) m/z 285.10224. Crystals suitable for X-ray crystallography
were grown from CH2Cl2/heptane.
a saturated aqueous solution of NH4Cl and diluted with CH2Cl2 (100 mL).
The organic layer was washed with a saturated aqueous solution of
NH4Cl (3 × 50 mL), dried with MgSO4, filtered, and the solvents were
removed in vacuo. The residue was subjected to flash column
chromatography (1) (SiO2 40–63 µm, loading: CS2, gradient elution
80−100% toluene/heptane), (2) (SiO2 40–63 µm, loading: CS2, 4%
EtOAc/CS2), which gave 5c (6 mg, 0.02 mmol, 4%) as a yellow solid.
TLC (toluene): Rf = 0.41. 1H NMR (500 MHz, CDCl3) δ 7.31 (d, J = 8.4 Hz,
2H), 7.10 (d, J = 8.2 Hz, 2H), 6.87 (d, J = 8.2 Hz, 2H), 6.80 (d, J = 8.4 Hz,
2H), 6.56 (dd, J = 11.1, 6.2 Hz, 1H), 6.49 (dd, J = 11.1, 5.9 Hz, 1H),
6.36–6.29 (m, 1H), 6.07 (d, J = 6.2 Hz, 1H), 5.79 (dd, J = 9.9, 4.1 Hz, 1H),
3.82 (s, 3H), 3.79 (s, 3H), 3.70–3.67 (m, 1H) ppm. 13C NMR (126 MHz,
CDCl3) δ 160.18, 160.00, 143.72, 140.51, 135.39, 131.35, 130.80,
130.45, 130.42, 127.55, 124.97, 124.23, 120.24, 119.53, 116.12, 114.46,
1,8a-Dihydro-3-(4’-methoxyphenyl)-2-(4’-nitrophenyl)azulene-1,1-
dicarbonitrile (5a). To a stirred solution of 3a (100 mg, 0.263 mmol) in a
mixture of toluene (18 mL) and water (2 mL) were added p-
methoxyphenylboronic acid (120 mg, 0.789 mmol), K3PO4 (112 mg,
0.526 mmol), BrettPhos (56 mg, 0.11 mmol), and Pd(OAc)2 (12 mg,
0.053 mmol). The reaction mixture was heated at 75 °C overnight, after
which it was diluted with CH2Cl2 (100 mL), washed with a saturated
aqueous solution of NH4Cl (3 × 50 mL), dried with MgSO4, filtered, and
the solvents were removed in vacuo. The residue was redissolved in
CH2Cl2, Celite was added and the mixture was concentrated. Purification
by dry column vacuum chromatography (SiO2 15–40 µm, 12.6 cm2, (1)
toluene/heptane, 0−60% 10% steps, 60–75%, 5% steps, 75–85%, 2.5%,
40 mL fractions), (2) THF/heptane 0−20%, 5% steps, 20– 37.5%, 2.5%
steps, 40 mL fractions) gave 5a (4 mg, 0.01 mmol, 4%) as a dark yellow
solid. TLC (75% CH2Cl2/heptanes): Rf = 0.64. M.p. 67–69 οC. 1H NMR
(400 MHz, CDCl3) δ 8.15 (d, J = 9.0 Hz, 2H), 7.54 (d, J = 9.0 Hz, 2H),
7.07 (d, J = 8.8 Hz, 2H), 6.88 (d, J = 8.8 Hz, 2H), 6.65–6.55 (m, 2H), 6.38
(ddd, J = 10.0, 4.6, 1.8 Hz, 1H), 6.21 (d, J = 5.0 Hz, 1H), 5.80 (dd, J =
10.0, 4.2 Hz, 1H), 3.82 (s, 3H), 3.73 (dt, J = 3.8, 1.7 Hz, 1H).13C NMR
(126 MHz, CDCl3) δ 160.74, 148.28, 147.65, 139.10, 138.63, 132.51,
131.90, 131.18, 130.75, 129.94, 127.85, 124.09, 123.51, 122.76, 119.64,
115.54, 114.81, 112.74, 55.48, 50.15, 46.72. HRMS (MALDI+ FT-ICR,
ditranol) m/z 406.11940 [M-H-], calcd. for (C25H16N3O3+) m/z 406.11862.
114.30, 113.38, 55.40, 55.40, 50.17, 47.12 ppm. HRMS (ESP+, FT-ICR,
+
TFA added) m/z 393.16150 [M+H+], calcd. for (C26H20N2O2
) m/z
393.15975.
2-(4’-Nitrophenyl)-3-phenylazulene-1-carbonitrile (6a). To a stirred
solution of 3a (92 mg, 0.242 mmol) in a mixture of toluene (18 mL) and
water (2 mL) were added p-methoxyphenylboronic acid (94 mg, 0.77
mmol), K3PO4 (101 mg, 0.476 mmol), BrettPhos (78 mg, 0.14 mmol), and
Pd(OAc)2 (17 mg, 0.076 mmol). The reaction mixture was heated at
85 °C overnight and then allowed to reach rt. A substantial amount of
starting material was left in the reaction mixture (judged by TLC) and it
was then flushed with Ar for 15 min with the help of sonication, and
additional p-methoxyphenylboronic acid (99 mg, 0.81 mmol), BrettPhos
(81 mg, 0.15 mmol), and Pd(OAc)2 (20 mg, 0.089 mmol) were added.
The reaction mixture was heated at 95 °C for one additional day, after
which it was diluted with CH2Cl2 (100 mL), washed with a saturated
aqueous solution of NH4Cl (3 × 50 mL), dried with MgSO4, filtered, and
the solvents were removed in vacuo. The residue was redissolved in
CH2Cl2, Celite was added and the mixture was concentrated in vacuo.
Purification by dry column vacuum chromatography (SiO2 15–40 µm,
12.6 cm2, toluene/heptane, 0−100%, 20% steps, 100% until the product
was eluted from the column, 40 mL fractions) gave 6a (15 mg, 0.043
mmol, 17%) as blue crystals. TLC (toluene): Rf = 0.26. 1H NMR (500
MHz, CDCl3) δ 8.78 (d, J = 9.8 Hz, 1H), 8.46 (d, J = 9.8 Hz, 1H), 8.20 (d,
J = 8.9 Hz, 2H), 7.90 (t, J = 9.8 Hz, 1H), 7.65–7.59 (m, 3H), 7.51 (t, J =
9.8 Hz, 1H), 7.45–7.39 (m, 3H), 7.25–7.22 (m, 2H) ppm. 13C NMR (126
MHz, CDCl3) δ 147.64, 147.61, 144.25, 141.12, 140.85, 140.28, 139.01,
137.67, 134.03, 131.34, 131.33, 130.40, 129.07, 128.74, 128.25, 127.99,
123.82, 117.26, 96.23 ppm. HRMS (ESP+, FT-ICR, TFA added) m/z
373.09518 [M+Na+], calcd. for (C23H14N2O2Na+) m/z 373.09475. Crystals
suitable for X-ray crystallography were grown from CH2Cl2/heptane.
1,8a-Dihydro-3-(4’-methoxyphenyl)-2-phenylazulene-1,1-
dicarbonitrile (5b). To a stirred solution of 3b (112 mg, 0.334 mmol) in a
mixture of toluene (18 mL) and water (2 mL) were added p-
methoxyphenylboronic acid (169 mg, 1.11 mmol), K3PO4 (155 mg, 0.730
mmol), BrettPhos (79 mg, 0.147 mmol), and Pd(OAc)2 (17 mg, 0.076
mmol). The reaction mixture was heated at 65 °C overnight, after which it
was quenched with a saturated aqueous solution of NH4Cl and diluted
with CH2Cl2 (100 mL). The organic layer was washed with a saturated
aqueous solution of NH4Cl (3 × 50 mL), dried with MgSO4, filtered, and
the solvents were removed in vacuo. The residue was subjected to flash
column chromatography (1) (SiO2 40–63 µm, loading: CS2, gradient
elution 80−100% toluene/heptane), (2) (SiO2 40–63 µm, loading: CS2,
13% EtOAc/heptane), which gave 5b (5 mg, 0.014 mmol, 4%) as a
yellow solid. TLC (toluene): Rf = 0.47, (15% EtOAc/heptanes): Rf = 0.31.
1H NMR (500 MHz, CDCl3) δ 7.41–7.36 (m, 2H), 7.32–7.28 (m, 3H), 7.10
(d, J = 8.7 Hz, 2H), 6.85 (d, J = 8.7 Hz, 2H), 6.58 (dd, J = 11.2, 6.2 Hz,
1H), 6.52 (dd, J = 11.1, 5.9 Hz, 1H), 6.35 (ddd, J = 9.9, 5.8, 2.0 Hz, 1H),
6.12 (d, J = 6.1 Hz, 1H), 5.81 (dd, J = 10.0, 4.2 Hz, 1H), 3.80 (s, 3H),
3.72–3.69 (m, 1H) ppm. 13C NMR (126 MHz, CDCl3) δ 160.10, 145.20,
140.14, 135.47, 131.97, 131.27, 130.82, 130.79, 129.26, 129.04, 128.82,
127.56, 124.54, 120.87, 119.65, 115.94, 114.38, 113.15, 55.38, 50.16,
47.26 ppm. HRMS (MALDI+ FT-ICR, ditranol) m/z 362.14150 [M•+], calcd.
for (C25H18N2O•+) m/z 362.14136.
3-(4’-Methoxyphenyl)-2-phenylazulene-1-carbonitrile (7b). To
a
stirred solution of 3b (90 mg, 0.27 mmol) in a mixture of toluene (18 mL)
and water (2 mL) were added phenylboronic acid (140 mg, 0.921 mmol),
K3PO4 (130 mg, 0.612 mmol), BrettPhos (89 mg, 0.081 mmol), and
Pd(OAc)2 (18 mg, 0.16 mmol). The reaction mixture was heated at 80 °C
overnight, after which it was quenched with a saturated aqueous solution
of NH4Cl and diluted with CH2Cl2 (100 mL). The organic layer was
washed with a saturated aqueous solution of NH4Cl (3 × 50 mL), dried
with MgSO4, filtered, and the solvents were removed in vacuo. The
residue was subjected to flash column chromatography (SiO2 40–63 µm,
loading: CS2, gradient elution 20% EtOAc/heptane), which gave 7b (24
mg, 0.072 mmol, 27%) as a blue solid and traces of 8b as a pink solid
both with minor impurities. Analytically pure samples were obtained by
recrystallization from CH2Cl2/heptane. 7b: TLC (toluene): Rf = 0.33. 1H
NMR (500 MHz, CDCl3) δ 8.66 (d, J = 9.8 Hz, 1H), 8.33 (d, J = 9.8 Hz,
1H), 7.75 (t, J = 9.8 Hz, 1H), 7.52 (t, J = 9.8 Hz, 1H), 7.45–7.35 (m, 6H),
7.29–7.26 (m, 2H), 6.88 (d, J = 8.9 Hz, 2H), 3.82 (s, 3H) ppm. 13C NMR
(126 MHz, CDCl3) δ 160.09, 151.01, 144.53, 140.33, 139.19, 136.94,
1,8a-Dihydro-2,3-bis(4’-methoxyphenyl)azulene-1,1-dicarbonitrile
(5c). To a stirred solution of 3c (150 mg, 0.410 mmol) in a mixture of
toluene (18 mL) and water (2 mL) were added p-methoxyphenylboronic
acid (207 mg, 1.36 mmol), K3PO4 (190 mg, 0.895 mmol), BrettPhos (105
mg, 0.196 mmol), and Pd(OAc)2 (21 mg, 0.094 mmol). The reaction
mixture was heated at 75 °C overnight, after which it was quenched with
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201601435
European Journal of Organic Chemistry
FULL PAPER
135.72, 135.19, 131.98, 131.36, 129.41, 128.77, 128.10, 127.65, 127.40,
126.51, 118.17, 114.19, 95.85, 55.39 ppm. HRMS (MALDI+ FT-ICR,
ditranol) m/z 358.12023 [M+Na+], calcd. for (C24H17NO+Na+) m/z
358.12024. 8b: TLC (toluene): Rf = 0.17 1H NMR (500 MHz, CDCl3) δ
8.81 (d, J = 10.0 Hz, 2H), 8.09 (t, J = 10.0 Hz, 1H), 8.06–8.03 (m, 2H),
7.87 (t, J = 10.0 Hz, 2H), 7.64–7.60 (m, 2H), 7.59–7.55 (m, 1H) ppm. 13C
NMR (126 MHz, CDCl3) δ 155.61, 145.44, 141.71, 138.14, 131.78,
131.67, 130.89, 129.65, 129.55, 116.10, 97.00 ppm. HRMS (ESP+, FT-
ICR, TFA added) m/z 277.07438 [M+Na+], calcd. for (C18H10N2Na+) m/z
277.07362.
starting material was left as judged by TLC (approximately 1 h). Then, by
cannula the solution was diluted with cold CH2Cl2 (80 mL) and at -40 °C a
solution of pyridine (0.35 mL, 4.3 mmol) in cold CH2Cl2 (20 mL) was
added dropwise. Upon addition of the first drop, the solution changed
color to the distinct red color of VHF. The reaction mixture was stirred for
an additional 3 h while letting the temperature voluntarily increase to rt in
which the reaction mixture turned brownish. The reaction mixture was
quenched with H2O (100 mL) and extracted with CH2Cl2 (3 x 50 mL),
dried with MgSO4, filtered, and the solvents were removed in vacuo. The
crude residue was dissolved in CH2Cl2, Celite was added and the mixture
was concentrated in vacuo. Purification by dry column vacuum
chromatography (SiO2 15-40 µm, 12.6 cm2, CH2Cl2/heptane, 0−100%
10% steps, followed by neat CH2Cl2, 40 mL fractions) gave 11c (52 mg,
0.13 mmol, 6%) as a yellow solid. TLC (75% CH2Cl2/heptanes), Rf = 0.36.
1H NMR (500 MHz, CDCl3) δ 8.22 (d, J = 8.9 Hz, 2H), 7.39 (d, J = 8.9 Hz,
2H), 7.27 (d, J = 8.9 Hz, 2H), 6.82 (d, J = 8.9 Hz, 2H), 6.59–6.51 (m, 2H),
6.39–6.34 (m, 1H), 5.98–5.94 (m, 1H), 5.82 (dd, J = 10.0, 4.0 Hz, 1H),
3.80 (s, 3H), 3.74 (dt, J = 4.0, 1.8 Hz, 1H) ppm. 13C NMR (126 MHz,
CDCl3) δ 160.86, 148.05, 141.82, 139.88, 139.04, 138.16, 131.28,
131.06, 130.68, 130.44, 127.87, 124.31, 122.96, 120.39, 119.49, 115.52,
114.68, 112.81, 55.46, 50.27, 47.34 ppm. Elem. anal. calc. for
C25H17N3O3 (407.13): C: 73.70%, H: 4.21%, N: 10.31%, found: C:
73.41%, H: 3.99%, N: 10.16%. HRMS (ESP+, FT-ICR, TFA added) m/z
406.11889 [M-H-], calcd. for (C25H16N3O3+) m/z 406.11862.
3-(4’-Methoxyphenyl)-2-(4’-methylphenyl)azulene-1-carbonitrile (10).
To a stirred solution of azulene 9 (64 mg, 0.20 mmol) in a mixture of
toluene (14 mL) and water (2 mL) were added p-methoxyphenylboronic
acid (71 mg, 0.467 mmol), K3PO4 (102 mg, 0.481 mmol), BrettPhos (46
mg, 0.086 mmol), and Pd(OAc)2 (9.4 mg, 0.042 mmol). The reaction
mixture was heated at 90 °C overnight, after which it was quenched with
water and diluted with ether (100 mL). The organic layer was washed
with water (3 × 50 mL), dried with MgSO4, filtered, and the solvents were
removed in vacuo. The residue was subjected to flash column
chromatography (SiO2 40–63 µm, loading: toluene, elution 20%
EtOAc/heptane), which gave 10 (65 mg, 0.17 mmol, 94%) as a blue solid.
TLC (toluene): Rf = 0.30, TLC (20% EtOAc/heptanes): Rf = 0.30. 1H NMR
(500 MHz, CDCl3) δ 8.66 (d, J = 9.7 Hz, 1H), 8.34 (d, J = 9.7 Hz, 1H),
7.75 (t, J = 9.7 Hz, 1H), 7.50 (t, J = 9.7 Hz, 1H), 7.42–7.36 (m, 3H), 7.21–
7.14 (m, 4H), 6.95 (d, J = 8.7 Hz, 2H), 3.86 (s, 3H), 2.36 (s, 3H) ppm. 13
C
4-Nitrophenyl acid chloride (13). p-Nitrophenyl acetic acid 12 (40.4 g,
223 mmol) was dissolved in CHCl3 (120 mL) in a 500 mL 3-necked flask
fitted with stoppers and a condenser connected with Dreschel bottles
containing an aqueous solution of NaOH (1 equiv.). SOCl2 (24 mL, 330
mmol) was added, and the solution was allowed to reflux until no gas
formation could be seen at the bubble counter. The reaction mixture was
cooled to rt and the excess SOCl2 was removed under vacuum affording
a brown gel containing the acid chloride 13. This compound was
dissolved in CS2 (200 mL) and the solution was split in two halves, which
were carried forward to the synthesis of 14b and 14c, respectively.
NMR (126 MHz, CDCl3) δ 159.00, 151.24, 144.35, 140.41, 139.37,
138.68, 137.28, 135.92, 132.41, 131.33, 130.41, 129.44, 129.40, 127.86,
127.44, 127.23, 118.09, 114.23, 96.08, 55.42, 21.52 ppm. HRMS (ESP+,
FT-ICR, TFA added) m/z 372.13648 [M+Na+], calcd. for (C25H19NONa+)
m/z 372.13589. Crystals suitable for X-ray crystallography were grown
from CH2Cl2/heptane.
1,8a-Dihydro-3-(4’-nitrophenyl)-2-phenylazulene-1,1-dicarbonitrile
(11b). To a stirring solution of 16b (1.18 g, 3.10 mmol) at -40 °C in dry
MeCN (25 mL) was added NOBF4 (788 mg, 6.75 mmol). The resulting
light brown solution was stirred at -40 °C (± 5°C) until no starting material
was left judged by TLC (approximately 1 h). Then, by cannula, the
solution was diluted with cold CH2Cl2 (80 mL) and at -40 °C a solution of
pyridine (0.55 mL, 6.8 mmol) in cold CH2Cl2 (20 mL) was dropwise added.
Upon the first drop, the solution changed color to the distinct red color of
VHF. The reaction mixture was stirred for an additional 3 h while letting
the temperature voluntarily increase to rt in which the reaction mixture
turned brownish. The reaction mixture was quenched with H2O (100 mL)
and extracted with CH2Cl2 (3 x 50 mL), dried with MgSO4, filtered, and
the solvents were removed in vacuo. The residue was redissolved in
CH2Cl2, Celite was added and the mixture was concentrated in vacuo.
Purification by dry column vacuum chromatography (SiO2, 15–40 µm,
12.6 cm2, toluene/heptane, 0−100% 10% steps, followed by neat toluene,
40 mL fractions) gave 11b (205 mg, 0.543 mmol, 17%) as a yellow solid.
TLC (toluene): Rf = 0.53. ppm. 1H NMR (500 MHz, CDCl3) δ 8.20 (d, J =
8.9 Hz, 2H), 7.39–7.31 (m, 7H), 6.61–6.56 (m, 2H), 6.41–6.35 (m, 1H),
6.00 (dd, J = 3.8, 1.7 Hz, 1H), 5.84 (dd, J = 9.8, 4.0 Hz, 1H), 3.76 (dt, J =
4.0, 1.8 Hz, 1H) ppm. 13C NMR (126 MHz, CDCl3) δ 148.14, 143.47,
139.39, 138.78, 138.31, 131.71, 130.99, 130.82, 130.63, 130.16, 129.23,
129.00, 127.94, 124.24, 121.11, 119.66, 115.32, 112.58, 50.25, 47.58
ppm. Elem. anal. calc. for C24H15N3O2 (377.12): C: 76.38%, H: 4.01%, N:
11.13%, found: C: 76.23%, H: 3.85%, N: 10.94%. HRMS (ESP+, FT-ICR,
TFA added) m/z 376.10816 [M+H-], calcd. for (C24H14N3O2+) 376.10805.
2-(4’-Nitrophenyl)-1-phenylethanone (14b).
A solution of 13 (111
mmol) in CS2 (100 mL) was cooled to 0 °C, and benzene (12 mL, 135
mmol) was added. Then, AlCl3 (18 g, 135 mmol) was added portionwise
at 0 °C. After the addition of AlCl3, the mixture was allowed to reach rt
and stirred for 14 h. The reaction mixture was cooled to 0 °C and
quenched with ice-cold water. The organic layer was separated and dried
with MgSO4, filtered, and concentrated in vacuo. Fractional
recrystallization from CH2Cl2/heptanes gave compound 14b (24.5 g, 102
mmol, 91% calculated from 12) as a white solid. M.p. 136−138 °C. 1H
NMR (500 MHz, CDCl3) δ 8.21 (d, J = 8.7 Hz, 2H), 8.01 (d, J = 7.6 Hz,
2H), 7.61 (t, J = 7.6 Hz, 1H), 7.50 (t, J = 7.6 Hz, 2H), 7.43 (d, J = 8.7 Hz,
2H), 4.42 (s, 2H) ppm. 13C NMR (126 MHz, CDCl3) δ 196.11, 147.23,
142.15, 136.31, 133.88, 130.78, 129.03, 128.59, 123.91, 45.09 ppm.
HRMS (MALDI+ FT-ICR, ditranol) m/z 272.09187 [M+H+], calcd. for
(C14H12NO3+) m/z 272.09173.
1-(4’-Methoxyphenyl)-2-(4’-nitrophenyl)-1-ethanon (14c). A solution of
13 (111 mmol) in CS2 (100 mL) was cooled to 0 °C, and anisole (14 mL,
130 mmol) was added. Then, anhydrous AlCl3 (18 g, 135 mmol) was
added portionwise at 0 °C resulting in an intense red coloration of the
mixture. After the addition of AlCl3, the mixture was allowed to reach rt
and stirred for 14 h. The reaction mixture was cooled to 0 °C and
quenched with ice-cold water. The organic layer was separated and dried
with MgSO4, filtered, and concentrated in vacuo. Then fractional
recrystallization from CH2Cl2/heptane and recrystallization from boiling
96% ethanol (500 mL) gave 14c (20.3 g, 74.7 mmol, 67% calculated from
12) as white crystals. M.p. 117−118 °C. 1H NMR (500 MHz, CDCl3) δ
8.19 (d, J = 8.6 Hz, 2H), 7.99 (d, J = 8.9 Hz, 2H), 7.43 (d, J = 8.6 Hz, 2H),
1,8a-Dihydro-2-(4’-methoxyphenyl)-3-(4’-nitrophenyl)azulene-1,1-
dicarbonitrile (11c). To a stirring solution of 16c (821 mg, 2.01 mmol) at
-40 °C in dry MeCN (25 mL) was added NOBF4 (500 mg, 4.28 mmol).
The resulting light brown solution was stirred at -40 °C (± 5°C) until no
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10.1002/ejoc.201601435
European Journal of Organic Chemistry
FULL PAPER
6.96 (d, J = 8.9 Hz, 2H), 4.35 (s, 2H), 3.88 (s, 3H) ppm. 13C NMR (126
MHz, CDCl3) δ 194.65, 164.11, 147.14, 142.62, 130.96, 130.70, 129.31,
123.87, 114.18, 55.70, 44.82 ppm. HRMS (ESP+, FT-ICR, TFA added)
m/z 272.09187 [M+H+], calcd. for (C15H14NO4+) 272.09173.
NMR (126 MHz, CDCl3) δ 179.35, 147.96, 142.75, 132.54, 131.74,
131.32, 130.86, 130.39, 128.85, 127.33, 126.47, 124.16, 121.51, 120.87,
112.02, 111.32, 90.58, 75.00, 53.28, 39.77 ppm. HRMS (MALDI+ FT-ICR,
ditranol) m/z 380.13951 [M+H+], calcd. for (C24H18N3O2+) m/z 380.13935.
Note 1) The addition of Et3N must be slow to avoid a build-up of a
strongly colored red anion.
2-(2-(4’-Nitrophenyl)-1-phenylethylidene)malononitrile (15b). To
a
stirring solution of 14b (9.62 g, 40.7 mmol) and malononitrile (13.2 g, 199
mmol) in toluene (240 mL) were added NH4OAc (15.4 g, 199 mmol) and
glacial acetic acid (29 mL, 507 mmol). The reaction vessel was equipped
with a Dean−Stark trap and refluxed for 48 h. When still warm, the
reaction mixture was decanted to discard an insoluble black oil and then
concentrated in vacuo. Et2O (300 mL) was added to this residue, which
was then washed with water (3 × 150 mL), dried with MgSO4 and the
organic phase was concentrated in vacuo. The crude residue was
dissolved in CH2Cl2, Celite was added and the mixture was concentrated
in vacuo. Purification by dry column vacuum chromatography (SiO2
15−40 µm, 113 cm2 CH2Cl2/heptanes, 0−100%, 10% steps, then neat
CH2Cl2 to collect product, 100 mL fractions) gave 15b (8.09 g, 27.7 mmol,
70%) as a thick dark oil. 1H NMR (500 MHz, CDCl3) δ 8.11 (d, J = 8.8 Hz,
2H), 7.54 (t, J = 7.6 Hz, 1H), 7.48 (t, J = 7.6 Hz, 2H), 7.41 (d, J = 7.6 Hz,
2H), 7.23 (d, J = 8.8 Hz, 2H), 4.38 (s, 2H) ppm. 13C NMR (126 MHz,
CDCl3) δ 175.39, 147.65, 141.62, 134.14, 132.70, 129.82, 129.58,
127.96, 124.42, 112.69, 112.26, 86.70, 42.81 ppm. HRMS (ESP+, FT-
ICR, TFA added) m/z 290.09279 [M+H+], calcd. for (C17H12N3O2+) m/z
290.09240.
2-(2-(Cyclohepta-2,4,6-trien-1-yl)-1-(4’-methoxyphenyl)-2-(4’-
nitrophenyl)ethylidene)malononitrile (16c). To a stirring suspension of
15c (2.09 g, 6.55 mmol) and freshly mortared tropylium tetrafluoroborate
(1.17 g, 6.58 mmol) in CH2Cl2 (125 mL) kept at -78 °C was added Et3N
(0.92 mL, 6.55 mmol) in CH2Cl2 (30 mL) slowly over 2 h. The reaction
mixture was stirred at -78 °C for 4 h, after which the reaction was
quenched, while cold, by addition of saturated aqueous NH4Cl (100 mL).
The organic layer was separated and washed with water (50 mL) and
brine (50 mL), dried with MgSO4, filtered, and concentrated in vacuo,
which gave 16c (2.20 g, 5.37 mmol, 82%) as a fluffy purple solid. TLC
(75% CH2Cl2/heptanes), Rf = 0.53. 1H NMR (500 MHz, CDCl3) δ 8.17 (d,
J = 8.7 Hz, 2H), 7.21 (d, J = 8.7 Hz, 2H), 6.84–6.79 (m, 1H), 6.81 (d, J =
8.9 Hz, 2H), 6.73 (dd, J = 10.9, 5.7 Hz, 1H), 6.66 (d, J = 8.9 Hz, 2H), 6.46
(dd, J = 9.4, 5.7 Hz, 1H), 6.19 (dd, J = 9.4, 5.7 Hz, 1H), 5.36 (dd, J = 9.4,
6.2 Hz, 1H), 4.99 (dd, J = 9.4, 6.2 Hz, 1H), 4.88 (d, J = 12.1 Hz, 1H), 3.79
(s, 3H), 2.43 (dt, J = 12.1, 6.2 Hz, 1H) ppm. 13C NMR (126 MHz, CDCl3)
δ 179.35, 161.73, 147.94, 143.18, 131.74, 131.34, 130.35, 129.29,
127.24, 126.43, 124.74, 124.21, 121.72, 120.92, 114.43, 112.40, 111.88,
89.80, 55.50, 53.41, 39.87 ppm. HRMS (MALDI+ FT-ICR, ditranol) m/z
410.150177 [M+H+], calcd. for (C25H20N3O3+) m/z 410.14992.
2-(1-(4'-Methoxyphenyl)-2-(4’-nitrophenyl)ethylidene)malononitrile
(15c). To a stirring solution of 14c (9.82 g, 36.2 mmol) and malononitrile
(11.3 g, 171 mmol) in toluene (240 mL) were added NH4OAc (13.2 g, 171
mmol) and glacial acetic acid (25 mL, 437 mmol). The reaction vessel
was equipped with a Dean−Stark trap and refluxed for 96 h. When still
warm, the reaction mixture was decanted to discard an insoluble black oil
and then concentrated in vacuo. Et2O (300 mL) was added to this
residue, which was then washed with water (3 × 150 mL), dried with
MgSO4 and the organic phase was concentrated in vacuo. The crude
residue was dissolved in CH2Cl2, Celite was added and the mixture was
concentrated in vacuo. Purification by dry column vacuum
chromatography (SiO2 15−40 µm 113 cm2, CH2Cl2/heptanes, 0−50%,
10% steps, 50-70%, 5%, 70−90 3% steps. 100 mL fractions) gave 15c
(7.55 g, 23.6 mmol, 65%) as white crystals. 1H NMR (500 MHz, CDCl3) δ
8.11 (d, J = 8.8 Hz, 2H), 7.51 (d, J = 9.0 Hz, 2H), 7.26 (d, J = 8.8 Hz, 2H),
6.97 (d, J = 9.0 Hz, 2H), 4.37 (s, 2H), 3.86 (s, 3H) ppm. 13C NMR (126
MHz, CDCl3) δ 174.06, 163.43, 147.47, 142.33, 130.44, 129.63, 125.98,
124.33, 114.99, 113.32, 113.16, 83.94, 55.73, 42.13 ppm. Elem. anal.
calc. for C18H13N3O3 (319.32): C: 67.71%, H: 4.10%, N: 13.16%, found:
C: 67.58%, H: 3.98%, N: 13.03%. HRMS (MALDI+ FT-ICR, ditranol) m/z
320.10364 [M+H+], calcd. for (C18H14N3O3+) m/z 320.10297.
Supporting Information
NMR spectra, X-ray crystallographic data, additional details on
the switching studies, and calculated structures and energies.
Acknowledgements
University of Copenhagen is acknowledged for financial support.
Prof. Anders Kadziola, University of Copenhagen, is
acknowledged for X-ray crystallographic analysis.
Keywords: Cyclization • Donor-acceptor systems • Fused-ring
systems • Kinetics • Photochromism
[1]
a) M. M. Russew, S. Hecht, Adv. Mater. 2010, 22, 3348-3360; b) T. J.
Kucharski, Y. Tian, S. Akbulatov, R. Boulatov, Energy Environ. Sci.
2011, 4, 4449-4472; c) W. Szymanski, J. M. Beierle, H. A. V.
Kistemaker, W. A. Velema, B. L. Feringa, Chem. Rev. 2013, 113, 6114-
6178; d) A. Gautier, C. Gauron, M. Volovitch, D. Bensimon, L. Jullien, S.
Vriz, Nature Chem, Biol. 2014, 10, 533-541; e) M. Irie, T. Fukaminato,
K. Matsuda, S. Kobatake, Chem. Rev. 2014, 114, 12174-12277; f) R.
Göstl, A. Senf, S. Hecht, Chem. Soc. Rev. 2014, 43, 1982-1996; g) A.
Lennartson, A. Roffey, K. Moth-Poulsen, Tetrahedron Lett. 2015, 56,
1457-1465.
2-(2-(Cyclohepta-2,4,6-trien-1-yl)-2-(4’-nitrophenyl)-1-
phenylethylidene)malononitrile (16b). To a stirring suspension of 15b
(2.08 g, 7.19 mmol) and freshly mortared tropylium tetrafluoroborate
(1.34 g, 7.55 mmol) in CH2Cl2 (125 mL) kept at -78 °C was added Et3N
(1.30 mL, 9.35 mmol) in CH2Cl2 (30 mL) slowly over 2 h (Note 1). The
reaction mixture was stirred at -78 °C for 4h, after which the reaction was
quenched, while cold, by addition of saturated aqueous NH4Cl (100 mL).
The organic layer was separated and washed with water (50 mL) and
brine (50 mL), dried with MgSO4, filtered, and concentrated in vacuo,
which gave 16b (2.55 g, 6.72 mmol, 93%) as a slightly yellow solid. TLC
(75% CH2Cl2/heptanes), Rf = 0.56. 1H NMR (500 MHz, CDCl3) δ 8.16 (d,
J = 8.7 Hz, 2H), 7.43 (t, J = 7.7 Hz, 1H), 7.31 (t, J = 7.7 Hz, 2H), 7.16 (d,
J = 8.7 Hz, 2H), 6.84 (dd, J = 11.0, 5.8 Hz, 1H), 6.73 (dd, J = 11.0, 5.8 Hz,
1H), 6.66 (d, J = 7.7 Hz, 2H), 6.50 (dd, J = 9.3, 5.3 Hz, 1H), 6.18 (dd, J =
9.3, 5.8 Hz, 1H), 5.42 (dd, J = 9.3, 6.2 Hz, 1H), 4.97 (dd, J = 9.3, 6.2 Hz,
1H), 4.90 (d, J = 12.0 Hz, 1H), 2.42 (dt, J = 12.0, 6.2 Hz, 1H) ppm. 13C
[2]
a) M. Cacciarini, S. L. Broman, Arkivoc 2014, I, 249-263; b) S. L.
Broman, M. B. Nielsen, Phys. Chem. Chem. Phys. 2014, 16, 21172-
21182.
[3]
[4]
J. Daub, T. Knöchel, A. Mannschreck, Ang. Chem. Int. Ed. 1984, 23,
960-961.
S. L. Broman, O. Kushnir, M. Rosenberg, A. Kadziola, J. Daub, M. B.
Nielsen, Eur. J. Org. Chem. 2015, 4119-4130.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201601435
European Journal of Organic Chemistry
FULL PAPER
[5]
[6]
[7]
M. Cacciarini, A. B. Skov, M. Jevric, A. S. Hansen, J. Elm, H. G.
Kjaergaard, K. V. Mikkelsen, M. B. Nielsen, Chem Eur. J. 2015, 21,
7454-7461.
C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M.
Klene, J. E. Knox, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R.
Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C.
Pomelli, J. W. Ochterski, R. L. Martin, K. Morokuma, V. G. Zakrzewski,
G. A. Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D. Daniels,
Ö. Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski, D. J. Fox,
Gaussian09 Revision D.01, Gaussian Inc. Wallingford CT, 2009.
[13] E. Cancès, B. Menunucci, J. Tomasi, J. Chem. Phys. 1997, 107, 3032-
3041.
a) L. P. Hammett, H. L. Pfluger, J. Am. Chem. Soc. 1933, 55, 4079-
4089; b) L. P. Hammett, Chem. Rev. 1935, 17, 125-136; c) L. P.
Hammett, J. Am. Chem. Soc. 1937, 59, 96-103.
a) M. Å. Petersen, S. L. Broman, K. Kilså, A. Kadziola, M. B. Nielsen,
Eur. J. Org. Chem. 2011, 1033-1039; b) S. L. Broman, M. Jevric, M. B.
Nielsen, Chem. Eur. J. 2013, 19, 9542-9548.
[8]
[9]
N. Shahzad, R. U. Nisa, K. Ayub, Struct. Chem. 2013, 24, 2115-2126.
T. Mrozek, H. Görner, J. Daub, Chem. Eur. J. 2001, 7, 1028-1040.
[14] T. Yanai, D. P. Tew, N. C. Handy, Chem. Phys. Lett. 2004, 393, 51-57.
[15] Y. Zhao, D. G. Truhlar, Theor. Chem. Acc. 2008, 120, 215-241.
[16] a) M. Ernzerhof, G. E. Scuseria, J. Chem. Phys. 1999, 110, 5029-5036;
b) C. Adamo, V. Barone, J. Chem. Phys. 1999, 110, 6158-6170.
[17] S. T. Olsen, J. Elm, F. E. Storm, A. N. Gejl, A. S. Hansen, M. H.
Hansen, J. R. Nikolajsen, M. B. Nielsen, H. G. Kjaergaard, K. V.
Mikkelsen, J. Phys. Chem. A 2015, 119, 896-904.
[10] V. Mazzanti, M. Cacciarini, S. L. Broman, C. R. Parker, M. Schau-
Magnussen, A. D. Bond, M. B. Nielsen, Beilstein J. Org. Chem. 2012, 8,
958-966.
[11] M. D. Kilde, S. L. Broman, A. Kadziola, M. B. Nielsen, Synlett 2016, 27,
450-454.
[12] M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb,
J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A.
Petersson, H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian, A. F.
Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada, M. Ehara, K.
Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O.
Kitao, H. Nakai, T. Vreven, J. A. Montgomery, Jr., J. E. Peralta, F.
Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N.
Staroverov, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J.
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10.1002/ejoc.201601435
European Journal of Organic Chemistry
FULL PAPER
Entry for the Table of Contents
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Y = EDG: fast
Y = EWG: slow
Hammett
correlation
NC
Hammett Correlations
CN
Ar
NC
NC
CN
Ar
NC
CN
ArH
CN
Ar
Martin Drøhse Kilde, Mia Harring
Hansen, Søren Lindbæk Broman, Kurt
V. Mikkelsen*, Mogens Brøndsted
Nielsen*
Br
or
COCl
VHF
DHA
(HO)2B
light
Y
Y
Y
Y
Page No. – Page No.
A selection of 2,3-diarylated dihydroazulenes (DHAs) was prepared and converted
upon irradiation to vinylheptafulvenes (VHFs). The kinetics of the ring-closure
reaction of the VHFs was found to follow Hammett correlations.
Expanding the Hammett Correlations
for the Vinylheptafulvene Ring-
Closure Reaction
This article is protected by copyright. All rights reserved.