Liquid crystalline dihydroazulene photoswitches

Article abstract of DOI:10.1039/c5ra18649h

A large selection of photochromic dihydroazulene (DHA) molecules incorporating various substituents at position 2 of the DHA core was prepared and investigated for their ability to form liquid crystalline phases. Incorporation of an octyloxy-substituted b

Full text of DOI:10.1039/c5ra18649h

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Liquid crystalline dihydroazulene photoswitches†
Anne Ugleholdt Petersen,a Martyn Jevric,a Richard J. Mandle,b Edward J. Davis,b
Cite this: RSC Adv., 2015, 5, 89731
b
b
a
*
Stephen J. Cowling, John W. Goodby and Mogens Brøndsted Nielsen
A large selection of photochromic dihydroazulene (DHA) molecules incorporating various substituents at
position 2 of the DHA core was prepared and investigated for their ability to form liquid crystalline
phases. Incorporation of an octyloxy-substituted biphenyl substituent resulted in nematic phase behavior
and it was possible to convert one such compound partly into its vinylheptafulvene (VHF) isomer upon
irradiation with light when in the liquid crystalline phase. This conversion resulted in an increase in the
molecular alignment of the phase. In time, the meta-stable VHF returns to the DHA where the alignment
is maintained. The systematic structural variation has revealed that a biaryl spacer between the DHA and
the alkyl chain is needed for liquid crystallinity and that the one aromatic ring in the spacer cannot be
substituted by a triazole. This work presents an important step towards employing the dihydroazulene-
vinylheptafulvene photo/thermoswitch in photoactive liquid crystalline materials.
Received 11th September 2015
Accepted 13th October 2015
DOI: 10.1039/c5ra18649h
www.rsc.org/advances
means that a broad spectrum of light can be used without
triggering the VHF to DHA back-reaction. The DHA ring-
1. Introduction
opening is associated with signicant changes in the physical
properties of the corresponding VHF. Thus, ring-opening is
associated with an increase in dipole moment and a change in
color from yellow (DHA) to intense red (VHF).8,9 We became
interested to elucidate if this difference in properties could give
rise to reversible, photochemically induced phase transitions.
Molecules with liquid crystalline properties can have
differing constructions, but for the purpose of this work,
attention was given to rod-like structures. Typically, rod-like,
liquid crystalline structures have two aliphatic chains extend-
ing from a rigid ‘core’ unit such as biphenyl or one alkyl chain
with an additional terminal substituent such as a nitrile.10 It
was decided to incorporate either a cyanophenyl-substituted
alkyl in the one end of DHA or an octyl chain. In the literature
there are many examples of the cyanobiphenyl being used as the
terminal substituent,11 but as this unit has absorption proper-
ties which conict with the wavelength needed for the ring-
opening event of DHA, the cyanophenyl substituent was used
predominantly in this study, as in structures 3a–e and 4a–e
(Fig. 1). Structures 3f–i and 4j instead have an octyl end-group.
Both cyanophenyl and octyl groups have been used previously to
achieve liquid crystallinity.12
In the eld of liquid crystals, it has been a goal to control the
phases and order with an external stimulus. Some of the stimuli
which have been applied include temperature, magnetic eld,
electric eld and light.1 Light is an interesting stimulus, since
this gives the possibility for remote control. Indeed, it has found
use in image storing devices.2,3 Specically, this has been shown
with azobenzene polymer matrix, where an image was stored for
8 months without signicant decay.2 Other photochromic
molecules such as dithienylethenes, spiropyrans and fulgides
have also shown suitable properties for this kind of applica-
tion.4–6 Here we present a study on liquid crystalline systems
based upon the dihydroazulene (DHA) photoswitch (Scheme 1).
When irradiated with light, DHA 1 undergoes a ring-opening to
the vinylheptafulvene (VHF) 2, which can then close back to the
initial DHA via a thermal electrocyclization reaction.7
The main advantage of the DHA–VHF photoswitch system is
that only the DHA to VHF conversion is light-induced, which
2. Results and discussion
Scheme 1 DHA 1/VHF 2 system.
2.1 Synthesis
The most convenient method for the construction of 2-
substituted DHAs originates from derivatized acetophenones.
Several strategies were undertaken in the pursuit of obtaining
the starting acetophenones (Scheme 2). From the simple
precursors 5a–e, 6, 7a–e, 8, acetophenones 9a–e were prepared
aDepartment of Chemistry, University of Copenhagen, Universitetsparken 5, DK-2100
Copenhagen Ø, Denmark. E-mail: mbn@chem.ku.dk
bDepartment of Chemistry, University of York, Heslington, York, YO10 5DD, UK
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c5ra18649h
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Fig. 1 DHAs employed in this study.
in two successive reactions. Thus, dibromoalkanes 5a–e of
various chain lengths were treated with phenols 6 and 8. Scheme 2 Synthesis of acetophenone starting materials. Conditions:
(a) K2CO3, acetone, reflux; (b) 5% Pd(PPh3)4, K3PO4, toluene/H2O, rt to
80 ꢀC; (c) FeCl3, AcCl, CH2Cl2, 0 ꢀC to rt.
Conversely, acetophenones containing biaryl units, 9f and 9g,
were obtained in good yields from a palladium-catalyzed Suzuki
cross-coupling reaction from 4-iodoacetophenone 10 with
boronic acids 11f and 11g, respectively, using conditions that
proved fruitful in the synthesis of the benzaldehyde
analogues.13 Finally, 9h could be formed in high yield by
a Friedel–Cras reaction of 12 with acetyl chloride using
a literature procedure.14 Compound 9i was purchased.
Acetophenones 9a–i could be transformed successfully into
the corresponding DHAs 3a–i (Scheme 3) by rstly converting
the carbonyl moiety into a crotononitrile unit in a Knoevenagel
condensation furnishing intermediates 13a–i, generally in good
yields. Intermediates 13a–i were then treated with tropylium
tetrauoroborate in the presence of triethylamine to affix the
cycloheptatriene unit to the malonitriles which could be further
converted into 3a–i by subsequent oxidation using tritylium
tetrauoroborate followed by treatment with triethylamine.
Alternatively, biaryl DHAs 3f and 3g could be obtained directly
from DHA 15 in a Suzuki reaction with boronic acids 11f and Scheme 3 Synthesis of DHAs. Conditions: (a) CH2(CN)2, NH4OAc,
toluene, AcOH, D. (b) [C7H7]BF4, NEt3, CH2Cl2, ꢁ78 ꢀC. (c) [Ph3C]BF4,
11g, using the catalytic system of palladium acetate and RuPhos
(Scheme 4). A separate strategy involving the introduction of the
CH2ClCH2Cl, D, then toluene, NEt3, 0 ꢀC.
extended chains could also be effected using the copper-
catalyzed azide–alkyne cycloaddition (CuAAC)15 to form tri-
We also decided to prepare the corresponding VHFs of two of
azole compounds. Triazoles have previously been incorporated
successfully into liquid crystalline compounds16 and, syntheti-
cally, DHA has been found to withstand the conditions.17 Alkyl
bromides 7a–e were converted into their corresponding azides
14a–e (Scheme 5) and when subjected to treatment with 10
the DHAs (to study their liquid crystalline properties of rele-
vance for the switching studies, vide infra). It has been shown
that DHA can be ring-opened by treatment with AlCl3 to afford
the corresponding VHF18 and this method could be used to
convert 3f into 17 in good yield (Scheme 6). When the method
was used on 3g, not only did the DHA undergo ring-opening to
¨
mol% cuprous iodide in the presence of 16 and Hunig's base,
triazoles 4a–e were achieved. DHA 4j could be made from
a CuAAC of octyl azide with 16 in the same manner.
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Table 1 Characteristic absorption maxima and kinetics data for VHF to
DHA conversions in acetonitrile at 25 ꢀC
DHA, lmax
(nm)
VHF, lmax
(nm)
VHF / DHA, k
VHF / DHA, t1/2
(min)
(10ꢁ5 sꢁ1
)
3a
3b
3c
3d
3e
3f
3g
3h
3i
4a
4b
4c
4d
4e
4j
365
366
367
366
365
374
366
359
358
370
370
370
368
370
369
469
470
471
470
470
474
475
480
471
475
476
475
475
475
475
5.04
5.00
4.97
4.97
4.97
6.78
7.30
5.00
4.98
6.65
6.72
6.72
6.68
6.66
6.63
229
231
232
232
232
170
158
231
232
174
172
172
173
174
174
Scheme
4 Functionalization of DHA via Suzuki cross-coupling.
Conditions: (a) Pd(OAc)2, RuPhos, K3PO4, toluene/H2O. RuPhos ¼ 2-
dicyclohexylphosphino-20,60-diisopropoxybiphenyl.
a formerly reported triazole functionalized DHA,17 which had
a rate constant for the VHF ring-closure of 7.45 ꢂ 10ꢁ5 sꢁ1. The
VHFs of 3h and 3i have comparable ring-closure rate constants
as those of the VHFs of 3a–e and of formerly reported DHA with
a p-methyl substituent. Inclusion of uorine seems to have no
effect for the VHF of 3h, or its effect is cancelled by the electron-
donating octyloxy substituent. For the biphenyls 3f and 3g the
rate of VHF to DHA conversion is higher and more similar to
that of 4a–e. Here the effect of the uorine is clear; the rate
increases to 7.30 ꢂ 10ꢁ5 sꢁ1 compared to the non-uorinated
Scheme 5 Functionalization of DHA via CuAAC. Conditions: (a) NaN3,
DMSO, 50 ꢀC; (b) CuI, Hunig's base, toluene.
¨
compound with a rate of 6.78 ꢂ 10ꢁ5 sꢁ1
.
2.3 Physical properties
The synthesized molecules were examined by polarized optical
microscopy (POM), but all starting materials en route to and
including DHAs 3a–e from the rst two approaches did not
show any liquid-crystalline properties. The same could also be
said for DHAs 4a–e and 4j. Instead, biaryl containing aceto-
phenones 9f and 9g and the corresponding DHAs 3f and 3g
exhibited a liquid-crystalline phase and were examined by both
POM and differential scanning calorimetry (DSC). Compound
9f was found to exhibit a mesophase. Indeed, 9f (Fig. 2) has
been previously reported with two different transitions, where
in one, it exhibited a smectic E phase,20 and in the other, a melt
Scheme 6 Synthesis of VHFs. Conditions (a) AlCl3, CH2Cl2, 0 ꢀC/rt,
then H2O, 0 ꢀC.
the VHF, but these reaction conditions also resulted in the
cleavage of the octyl chain to form phenol 18.
2.2 Photochemical properties
All DHAs made in this study show photoactive properties akin was reported at 115–118 C.21 We found that under the micro-
to that of unfunctionalized DHA 1. All DHAs exhibited an scope 9f did exhibit a smectic phase (see Fig. 2), in agreement
absorption maximum at around 360 nm and when irradiated with the former report although denitive phase assignment
with light of this wavelength, they undergo an electrocyclic ring- was not possible due to the short range of supercooling. Hence,
opening reaction. Thereby a peak at 475 nm emerges, corre- we denote it smectic X. Fig. 3 shows the DSC thermogram.
ꢀ
sponding to the formation of the VHF (Table 1). The rate of VHF
DSC showed a transition for a mesophase, where the size of
to DHA thermal ring-closure has been found to be inuenced the associated enthalpy to the phase transition is indicative of
greatly by the introduction of electron-donating/accepting the formation of a smectic mesophase. The partially uorinated
functional groups.9,19 The VHFs of DHAs 3a–e all exhibit a rate analogue 9g gave a lower melt and did not exhibit a liquid-
constant corresponding to that of the p-methoxy substituted crystalline phase during the heating process. Upon cooling,
derivative of DHA 1. The rate of ring-closure for the VHFs of the a peak corresponding to a liquid-crystalline phase could only be
ꢀ
triazole derivatives 4a–e and 4j show a small deviation from observed in the DSC at 53.8 C. It was only possible to observe
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Table 2 Transition temperatures (ꢀC) for compounds 9f and 9g
Transition temperatures (ꢀC)
9f
9g
Cr 91.0 SmX 128 Iso
Cr 63.2 Iso
Iso 130.2 SmX 79.5 Cr
Iso 53.8 SmX 48.8 Cr
Table 3 Enthalpies (kJ molꢁ1) and dimensionless entropies associated
with transitions for compounds 9f and 9g
Fig. 2 Photomicrographs of the smectic X phase of 9f at 118 ꢀC.
Cr-Iso
Cr-SmX
SmX-Iso
Iso-SmX
SmX-Cr
9f
DH
DS/R
DH
—
—
25.91
9.265
23.48
7.755
—
13.377
4.0106
—
12.54
3.739
2.713
0.9980
24.10
8.819
22.95
8.574
9g
DS/R
—
—
to demonstrate liquid crystalline properties. Neither 3f nor 3g
exhibited a mesophase in the rst heating cycle, but upon
cooling, a nematic phase appeared (Fig. 4). Further cooling did
not result in crystallization, instead a glass transition occurred
and when reheating the glass, the nematic phase reappeared
and the transition from nematic to isotropic liquid could also
Fig. 3 (Top) DSC thermograms at a heating–cooling rate of 10 ꢀC
minꢁ1 for compound 9f. (Bottom) DSC thermograms at a heating–
cooling rate of 5 ꢀC minꢁ1 for compound 9g, where the dashed line is
the first heating.
this phase when the sample had been heated to 100 ꢀC prior to
cooling. When compound 9g was heated to a lesser extent, such
as 67 or 80 ꢀC, the sample underwent crystallization during the
cooling phase prior to the temperature where this initial phase
transition was observed. When examined by POM, the crystal-
lization occurred prior to the liquid crystal phase transition
temperature. Table 2 lists transition temperatures for 9f and 9g
and Table 3 the enthalpies and entropies associated with the
transitions.
The two DHAs 3f and 3g showed liquid crystalline properties,
whilst 3h and 3i did not exhibit any mesophases. This suggests
that the additional aryl ring is important for the modied DHAs
Fig. 4 DSC thermograms at a heating-cooling rate of 5 ꢀC minꢁ1 for
compound 3f (Top) and compound 3g (Bottom). The dashed line
corresponds to the first heating.
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be observed. DHA 3f gave a melt at 90.6 ꢀC and the nematic has a larger dipole moment, which could in essence lead to this
phase appeared upon cooling at 75.7 ꢀC, see Fig. 4. On heating, larger degree of alignment of the total system relative to the
ꢀ
the clearing point was found to be at 75.6 C. The phase tran- corresponding neat nematic DHA. There are several examples in
sitions showed small enthalpy changes, which agrees with the the literature22 with photoalignment; the difference is that our
changes from nematic to liquid phase and vice versa. For the experiment was performed in between untreated glass slides,
uorinated 3g analogue, the melt occurred at a temperature which gives a texture. This texture then disappears upon irra-
about 10 ꢀC lower than for 3f. The clearing point for the nematic diation. On the other hand, when heating pure VHF 17, no
ꢀ
phase of 3g is 52.6 C, while it is 75.7 ꢀC for 3f. Table 4 lists mesophases were observed for VHF 17, instead a rapid ring-
transition temperatures for 3f and 3g and Table 5 the enthalpies closure to 3f occurred.
and entropies associated with the transitions.
When 3f is irradiated (at 365 nm) in the nematic phase,
a color change from yellow-orange to red can be observed by the
3. Conclusions
naked eye, but this did not correspond to a change in the In order to ascertain the requirements of substitution needed to
phases. When solid VHF 17 was heated to 40 ꢀC for 24 h, neither make the DHA photoswitch liquid crystalline, we have prepared
a change in color nor a phaseꢀchange was observed, while a large selection of compounds with various substituents at
heating the same material to 80 C resulted in a simultaneous position 2 of the DHA core. Of these compounds, two exhibited
melt and color change to yellow ascribed to conversion to the a nematic liquid crystal phase, both of which had an octyloxy-
DHA state. When 3g was irradiated with light in the nematic biaryl attached to C2 of DHA. Irradiation of the one compound,
phase at 40 ꢀC for 60 min, conversion to the corresponding VHF with uorine substitution of the biaryl, in its nematic phase
occurred in a ratio of 3 : 7 (VHF/DHA) as determined by NMR partly formed the VHF. This DHA/VHF mixture exhibited
spectroscopy. Aer one hour of irradiation, using POM one a higher degree of alignment. In time, the DHA was regenerated
could see an increase in the alignment of the nematic phase, and the order maintained. Nevertheless, full conversion to the
such that the defects disappear (Fig. 5c). Irradiation for a pro- VHF from the DHA in the nematic phase was not possible. This
longed period (16 hours) afforded no further changes in neither work presents an important step in using the DHA–VHF system
the POM picture nor in the isomer ratio determined by NMR in photoactive liquid crystalline materials. Future work will be
spectroscopy. When le in the dark to reclose to form the DHA, aiming at exploring the inuence of having two substituent
the alignment is maintained. If the top glass slide is sheared groups on the DHA core.
horizontally to disrupt the alignment, the nematic texture
appears for the DHA, (Fig. 5d). If the same disruption is done
with the VHF present, the alignment reforms over several
minutes. In addition to the VHF structure being planar, it also
4. Experimental
4.1 General methods
Chemicals were used as purchased from commercial sources.
Purication of products was carried out by ash chromatog-
˚
raphy on silica gel (40ꢁ63 mm, 60 A). Thin-layer chromatog-
Table 4 Transition temperatures (ꢀC) for compounds 3f and 3g
raphy (TLC) was carried out using aluminum sheets precoated
with silica gel. 1H NMR (500 MHz) and 13C NMR (125 MHz)
spectra were recorded on an instrument with a noninverse
cryoprobe using the residual solvent as the internal standard
(CDCl3, 1H 7.26 ppm and 13C 77.16 ppm). All chemical shis are
quoted on the d scale (ppm), and all coupling constants (J) are
expressed in Hz. In APT spectra, CH and CH3 correspond to
negative signals and C and CH2 correspond to positive signals.
High resolution mass spectra (HRMS) were acquired either
Transition temperatures (ꢀC)
using an electrospray method of ionization (ESP) or using
MALDI. Melting points are uncorrected. Compounds 15 (ref. 23)
and 16 (ref. 24) were made by their respective literature
methods.
3f
3g
Cr 90.6 (Tg 29.8 N 75.7) Iso
Cr 79.9 (Tg 30.8 N 52.6) Iso
General procedure for 7a–e. A mixture consisting of 4-cya-
nophenol 6, the dibromide 5 (either a–e; 2–2.5 molar equiva-
lents) and K2CO3 (1.5–2 molar equivalents) in acetone (200 mL)
was heated to reux point for 16 h. The contents of the vessel
were allowed to cool to rt and ltered. The solvent was removed
from the ltrate and the crude residue was subjected to column
chromatography (gradient elution of petroleum spirit to
toluene) to afford 7 (either a–e) as a white solid.
Table
5
The enthalpies (kJ molꢁ1) and dimensionless entropies
associated with transition for compound 3f and 3g
N-Iso
Cr-Iso
Iso-N
3f
DH
DS/R
DH
0.4612
0.1590
0.4526
0.1671
30.53
10.09
31.70
10.80
0.4044
0.1394
0.4057
0.1498
3g
4-((5-Bromopentyl)oxy)benzonitrile (7a). Mp ¼ 54.0–55.9 ꢀC. 1H
NMR (500 MHz, CDCl3): d ¼ 7.57 (d, J ¼ 8.8 Hz, 2H), 6.93 (d, J ¼
DS/R
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Fig. 5 (a) Photomicrographs of the nematic phase of 3f at 60 ꢀC. (b–d) Photomicrographs of the nematic phase of 3g at 40 ꢀC, (b) before light, (c)
after 60 min of light, (d) after dark for 16 h.
8.8 Hz, 2H), 4.01 (t, J ¼ 6.3 Hz, 2H), 3.44 (t, J ¼ 6.7 Hz, 2H), 1.97– calcd (%) for C15H20BrNO (310.24): C 58.07, H 6.50, N 4.51;
1.91 (m, 2H), 1.87–1.81 (m, 2H), 1.67–1.60 (m, 2H) ppm. 13C found: C 58.26, H 6.53, N 4.51.
NMR (125 MHz, CDCl3): d ¼ 162.4, 134.1, 119.4, 115.3, 104.0,
4-((9-Bromononyl)oxy)benzonitrile (7d). Rf ¼ 0.50 (toluene). Mp
68.1, 33.6, 32.5, 28.3, 24.8 ppm. MS (ESP +ve): m/z ¼ 290 [(M + ¼ 64.1–65.7 ꢀC. 1H NMR (500 MHz, CDCl3): d ¼ 7.55 (d, J ¼ 8.9
Na)+]. Analysis calcd (%) for C12H14BrNO (268.15): C 53.75, H Hz, 2H), 6.91 (d, J ¼ 8.9 Hz, 2H), 3.98 (t, J ¼ 6.5 Hz, 2H), 3.39 (t, J
5.26, N 5.22; found: C 53.75, H 4.90, N 5.13.
¼ 6.5 Hz, 2H), 1.86–1.75 (m, 4H), 1.46–1.39 (m, 4H), 1.36–1.29
4-((6-Bromohexyl)oxy)benzonitrile (7b). Mp ¼ 44.0–46.5 ꢀC. 1H (m, 6H) ppm. 13C NMR (125 MHz, CDCl3): d ¼ 162.5, 134.0,
NMR (500 MHz, CDCl3): d ¼ 7.57 (d, J ¼ 8.9 Hz, 2H), 6.93 (d, J ¼ 119.4, 115.2, 103.7, 68.4, 34.1, 32.8, 29.3, 29.2, 29.0, 28.7, 28.2,
8.9 Hz, 2H), 4.00 (t, J ¼ 6.4 Hz, 2H), 3.43 (t, J ¼ 6.6 Hz, 2H), 1.90 25.9 ppm. MS (ESP +ve): m/z ¼ 324 [(M + H)+]. Analysis calcd (%)
(p, J ¼ 6.6 Hz, 2H), 1.82 (p, J ¼ 6.6 Hz, 2H), 1.53–1.50 (m, 4H) for C16H22BrNO (324.26): C 59.27, H 6.84, N 4.32; found: C
ppm. 13C NMR (125 MHz, CDCl3): d ¼ 162.5, 134.1, 119.4, 115.3, 59.52, H 6.93, N 4.32.
103.9, 68.3, 33.8, 32.7, 29.0, 28.0, 25.3 ppm. MS (ESP +ve): m/z ¼
4-((10-Bromodecyl)oxy)benzonitrile (7e). Rf ¼ 0.50 (toluene).
282 [(M + H)+]. Analysis calcd (%) for C13H16BrNO (282.18): C Mp ¼ 73.2–74.7 ꢀC. 1H NMR (500 MHz, CDCl3): d ¼ 7.57 (d, J ¼
55.33, H 5.72, N 4.96; found: C 55.66, H 5.72, N 4.98.
8.9 Hz, 2H), 6.93 (d, J ¼ 8.9 Hz, 2H), 3.99 (t, J ¼ 6.5 Hz, 2H), 3.41
4-((8-Bromooctyl)oxy)benzonitrile (7c). Rf ¼ 0.50 (toluene). Mp (t, J ¼ 6.8 Hz, 2H), 1.88–1.77 (m, 4H), 1.48–1.40 (m, 4H), 1.36–
¼ 68.5–69.8 ꢀC. 1H NMR (500 MHz, CDCl3): d ¼ 7.57 (d, J ¼ 8.8 1.28 (m, 8H) ppm. 13C NMR (125 MHz, CDCl3): d ¼ 162.6, 134.1,
Hz, 2H), 6.93 (d, J ¼ 8.8 Hz, 2H), 3.99 (t, J ¼ 6.5 Hz, 2H), 3.41 (t, J 119.5, 115.3, 103.8, 68.5, 34.2, 32.9, 29.5, 29.5, 29.4, 29.1, 28.9,
¼ 6.8 Hz, 2H), 1.89–1.84 (m, 2H), 1.82–1.77 (m, 2H), 1.49–1.42 28.3, 26.1 ppm. MS (ESP +ve): m/z ¼ 360 [(M + Na)+]. Analysis
(m, 4H), 1.39–1.33 (m, 4H) ppm. 13C NMR (125 MHz, CDCl3): d ¼ calcd (%) for C17H24BrNO (338.29): C 60.36, H 7.15, N 4.14;
162.5, 134.1, 119.4, 115.3, 103.8, 68.5, 34.1, 32.9, 29.2, 29.1, 28.8, found: C 60.53, H 7.19, N 4.15.
28.2, 26.0 ppm. MS (ESP +ve): m/z ¼ 310 [(M + H)+]. Analysis
General procedure for 9a–e. A mixture consisting of 4-
hydroxyacetophenone 8, bromide 7 (either a–e; 0.8–0.85 molar
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equivalents) and K2CO3 (1–2 molar equivalents) in acetone (100 394.2377; exp 394.2377. Analysis calcd (%) for C25H31NO3
mL) was heated to reux point for 24 h. The contents of the (393.53): C 76.30, H 7.94, N 3.56; found: C 76.29, H 7.90, N 3.52.
vessel were allowed to cool to rt, diluted with CH2Cl2 (200 mL)
1-(40-(Octyloxy)-[1,10-biphenyl]-4-yl)ethan-1-one (9f).20,21 To
and ltered. The solvent was removed from the ltrate and the a degassed biphasic mixture of 4-iodoacetophenone 10 (5.03 g,
crude residue was passed through a short SiO2 column (CH2Cl2) 20.4 mmol), K3PO4 (11.94 g, 56.71 mmol) and 11f (6.43 g, 25.7
to afford 9 (either a–e) as a white solid.
mmol) in toluene (120 mL) and water (20 mL) was added
4-((5-(4-Acetylphenoxy)pentyl)oxy)benzonitrile (9a). Rf ¼ 0.39. Pd(PPh3)4 (1.00 g, 0.86 mmol) and the biphasic mixture was
Mp ¼ 100.8–102.8 ꢀC. 1H NMR (500 MHz, CDCl3): d ¼ 7.96 (d, J stirred 20 h at rt and heated to 80 ꢀC for 10 h. The reaction
¼ 8.9 Hz, 2H), 7.60 (d, J ¼ 8.9 Hz, 2H), 6.93 (d, J ¼ 8.9 Hz, 2H), mixture was cooled to rt and was diluted with water (80 mL) and
6.92 (d, J ¼ 8.9 Hz, 2H), 4.06 (t, J ¼ 6.2 Hz, 2H), 4.04 (t, J ¼ 6.3 Hz, the phases were separated. The aqueous phase was extracted
2H), 2.55 (s, 3H), 1.92–1.87 (m, 4H), 1.70–1.64 (m, 2H) ppm. 13
C
with CH2Cl2 (2 ꢂ 50 mL) and the combined organic extracts
NMR (125 MHz, CDCl3): d ¼ 196.9, 163.0, 162.4, 134.1, 130.7, dried over MgSO4, ltered and the solvent removed in vacuo.
130.4, 119.4, 115.3, 114.2, 104.0, 68.2, 68.0, 29.0, 28.9, 26.5, 22.8 The solid was triturated with CH2Cl2 and heptane to give 9f
ppm. HRMS (MALDI +ve) calcd for C20H22NO3 ([M + H]+): m/z ¼ (5.73 g, 86%) as an off white solid. Rf ¼ 0.41 (toluene). Mp ¼ Cr
324.1594; exp 324.1595. Analysis calcd (%) for C20H21NO3 91.0 SmX 128 Iso; Iso 130.2 SmX 79.5 Cr ꢀC. 1H NMR (500 MHz,
(323.39): C 74.28, H 6.55, N 4.33; found: C 74.09, H 6.28, N 4.27. CDCl3): d ¼ 8.00 (d, J ¼ 8.4 Hz, 2H), 7.64 (d, J ¼ 8.4 Hz, 2H), 7.57
4-((6-(4-Acetylphenoxy)hexyl)oxy)benzonitrile (9b). Rf ¼ 0.33. (d, J ¼ 8.6 Hz, 2H), 6.99 (d, J ¼ 8.6 Hz, 2H), 4.01 (t, J ¼ 6.5 Hz,
Mp ¼ 99.5–101.3 ꢀC. 1H NMR (500 MHz, CDCl3): d ¼ 7.92 (d, J ¼ 2H), 2.63 (s, 3H), 1.84–1.78 (m, 2H), 1.50–1.45 (m, 2H), 1.42–1.20
8.9 Hz, 2H), 7.57 (d, J ¼ 8.9 Hz, 2H), 6.93 (d, J ¼ 8.9 Hz, 2H), 6.91 (m, 8H), 0.89 (t, J ¼ 6.8 Hz, 3H) ppm. 13C NMR (125 MHz,
(d, J ¼ 8.9 Hz, 2H), 4.04 (t, J ¼ 6.4 Hz, 2H), 4.02 (t, J ¼ 6.4 Hz, CDCl3): d ¼ 197.9, 159.7, 145.6, 135.4, 132.1, 129.1, 128.5, 126.7,
2H), 2.55 (s, 3H), 1.87–1.82 (m, 4H), 1.57–1.55 (m, 4H) ppm. 13
C
115.1, 68.3, 32.0, 29.5, 29.4, 26.8, 26.2, 22.8, 14.3 ppm, 1C
NMR (125 MHz, CDCl3): d ¼ 196.9, 163.1, 162.5, 134.1, 130.7, masked. HRMS (MALDI +ve) calcd for C22H28O2Na [(M + Na)+]:
130.4, 119.4, 115.3, 114.2, 103.9, 68.3, 68.1, 29.2, 29.1, 26.5, 25.9, m/z ¼ 347.1982; exp 347.1991. Analysis calcd (%) for C22H28O2
25.9 ppm. HRMS (MALDI +ve) calcd for C21H24NO3 ([M + H]+): (324.46): C 81.44, H 8.70; found: C 80.99, H 8.42.
m/z ¼ 338.1751; exp 338.1751. Analysis calcd (%) for C21H23NO3
1-(20,30-Diuoro-40-(octyloxy)-[1,10-biphenyl]-4-yl)ethan-1-one (9g).
(337.42): C 74.75, H 6.87, N 4.15; found: C 74.60, H 6.73, N 3.99. To a degassed biphase of 4-iodoacetophenone 10 (5.20 g, 21.1
4-((8-(4-Acetylphenoxy)octyl)oxy)benzonitrile (9c). Rf ¼ 0.35. Mp mmol) in toluene (120 mL) and water (20 mL) were added
¼ 91.1–92.3 ꢀC. 1H NMR (500 MHz, CDCl3): d ¼ 7.92 (d, J ¼ 8.9 Pd(PPh3)4 (1.00 g, 0.86 mmol), K3PO4 (14.90 g, 70.2 mmol) and
Hz, 2H), 7.56 (d, J ¼ 8.8 Hz, 2H), 6.92 (d, J ¼ 8.9 Hz, 2H), 6.91 (d, 11g (9.08 g, 31.7 mmol) and the biphasic mixture was stirred
J ¼ 8.8 Hz, 2H), 4.02 (t, J ¼ 6.5 Hz, 2H), 3.99 (d, J ¼ 6.5 Hz, 2H), 20 h at rt, followed by heating at 80 ꢀC for 7 h. The reaction was
2.55 (s, 3H), 1.84–1.78 (m, 4H), 1.50–1.45 (m, 4H), 1.41–1.38 (m, allowed to cool to rt and the vessel was diluted with water
4H) ppm. 13C NMR (125 MHz, CDCl3): d ¼ 196.9, 163.2, 162.5, (80 mL) and the phases were separated. The aqueous phase was
134.1, 130.7, 130.3, 119.4, 115.3, 114.2, 103.8, 68.5, 68.3, 29.4, extracted with CH2Cl2 (2 ꢂ 50 mL) and the combined organic
29.4, 29.2, 29.1, 26.5, 26.1, 26.0 ppm. HRMS (MALDI +ve) calcd phases dried over MgSO4, ltered and the solvent removed in
for C23H28NO3Na ([M + Na]+): m/z ¼ 388.1883; exp 388.1884. vacuo. The residue was subjected to ash column chromatog-
Analysis calcd (%) for C23H27NO3 (365.47): C 75.59, H 7.45, N raphy (gradient elution of 50–80% CH2Cl2/heptane) and tritu-
3.83; found: C 75.51, H 7.28, N 3.78.
rated from CH2Cl2 and heptane to give 9g (5.01 g, 66%) as
4-((9-(4-Acetylphenoxy)nonyl)oxy)benzonitrile (9d). Rf ¼ 0.35. a white solid. Rf ¼ 0.51 (toluene). Mp ¼ Cr 63.2 Iso; Iso 53.8 SmX
1
1
Mp ¼ 86.4–87.2 ꢀC. H NMR (500 MHz, CDCl3): d ¼ 7.92 (d, J ¼ 48.8 Cr C. H NMR (500 MHz, CDCl3): d ¼ 8.02 (d, J ¼ 7.9 Hz,
8.6 Hz, 2H), 7.57 (d, J ¼ 8.6 Hz, 2H), 6.93 (d, J ¼ 8.6 Hz, 2H), 6.91 2H), 7.61 (d, J ¼ 7.9 Hz, 2H), 7.13 (td, J ¼ 8.4, 2.2 Hz, 1H), 6.82
(d, J ¼ 8.6 Hz, 2H), 4.02 (t, J ¼ 6.5 Hz, 2H), 3.99 (t, J ¼ 6.5 Hz, (td, J ¼ 8.4, 1.6 Hz, 1H), 4.09 (t, J ¼ 6.5 Hz, 2H), 2.64 (s, 3H),
2H), 2.55 (s, 3H), 1.83–1.77 (m, 4H), 1.49–1.43 (m, 4H), 1.39–1.35 1.87–1.82 (m, 2H), 1.51–1.45 (m, 2H), 1.43–1.22 (m, 8H), 0.89 (t, J
(m, 6H) ppm. 13C NMR (125 MHz, CDCl3): d ¼ 196.9, 163.2, ¼ 6.9 Hz, 3H) ppm. 13C NMR (125 MHz, CDCl3): d ¼ 197.8, 149.1
162.6, 134.1, 130.7, 130.3, 119.5, 115.3, 114.3, 103.8, 68.5, 68.3, (dd, J ¼ 249.8, 11.22 Hz), 148.8 (dd, J ¼ 8.3, 3.1 Hz), 141.9 (dd, J
29.6, 29.4, 29.4, 29.2, 29.1, 26.5, 26.1, 26.1 ppm. HRMS (MALDI ¼ 248.2, 14.9 Hz), 139.8 (dd, J ¼ 2.8, 1.9 Hz), 136.2, 129.0 (d, J ¼
+ve) calcd for C24H30N3O2 ([M + H]+): m/z ¼ 380.2220; exp 3.1 Hz), 128.7, 123.8 (t, J ¼ 4.1 Hz), 121.8 (d, J ¼ 10.7 Hz), 109.8
380.2221. Analysis calcd (%) for C24H29NO3 (379.50): C 75.96, H (dd, J ¼ 3.2, 0.9 Hz), 70.1, 32.0, 29.4, 29.4, 29.3, 26.8, 26.0, 22.8,
ꢀ
7.70, N 3.69; found: C 75.82, H 7.68, N 3.55.
14.2 ppm. HRMS (MALDI +ve) calcd for C22H26F2O2Na [(M +
4-((10-(4-Acetylphenoxy)decyl)oxy)benzonitrile (9e). Rf ¼ 0.40. Na)+]: m/z ¼ 383.1793; exp 383.1805. Analysis calcd (%) for
Mp ¼ 71.5–73.5 ꢀC. 1H NMR (500 MHz, CDCl3): d ¼ 7.92 (d, J ¼ C22H26F2O2 (360.44): C 73.31, H 7.27; found: C 73.25, H 7.34.
8.8 Hz, 2H), 7.56 (d, J ¼ 8.8 Hz, 2H), 6.92 (d, J ¼ 8.8 Hz, 2H), 6.91
2,3-Diuoro-4-(octyloxy)acetophenone (9h).14 To a degassed
(d, J ¼ 8.8 Hz, 2H), 4.01 (t, J ¼ 6.5 Hz, 2H), 3.99 (d, J ¼ 6.5 Hz, solution of 12 (6.22 g, 25.7 mmol) and FeCl3 (5.32 g, 32.8 mmol)
2H), 2.55 (s, 3H), 1.83–1.76 (m, 4H), 1.48–1.42 (m, 4H), 1.37–1.32 in CH2Cl2 (150 mL), under argon and in an ice bath, was added
(m, 8H) ppm. 13C NMR (125 MHz, CDCl3): d ¼ 196.9, 163.2, a solution of acetyl chloride (2.1 mL in 50 mL CH2Cl2, 29.4
162.6, 134.1, 130.7, 130.3, 119.4, 115.3, 114.2, 103.8, 68.5, 68.4, mmol) dropwise over a period of 80 min. The resulting mixture
29.6, 29.4, 29.4, 29.2, 29.1, 26.5, 26.1, 26.1 ppm, 1C masked. was stirred for 22 h during which time the vessel was allowed to
HRMS (MALDI +ve) calcd for C25H32NO3 ([M + H]+): m/z ¼ reach rt. The reaction was quenched with water (500 mL) and
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the phases separated. The aqueous phase was extracted with 1.54–1.48 (m, 4H), 1.46–1.41 ppm. 13C NMR (125 MHz, CDCl3): d ¼
CH2Cl2 (100 mL) and the combined organic extracts were 174.2, 162.8, 162.5, 134.1, 130.0, 127.7, 119.5, 115.2, 114.9, 113.9,
washed with saturated aqueous saturated NaHCO3 (200 mL), 113.6, 103.7, 81.8, 68.4, 29.4, 29.1, 29.1, 26.0, 26.0, 24.0 ppm.
dried over MgSO4, ltered and concentrated in vacuo. The HRMS (MALDI +ve) calcd for C26H28N3O2 ([M + H]+): m/z ¼
residue was puried by ash column chromatography (gradient 414.2176; exp 414.2177. Analysis calcd (%) for C26H27N3O2
elution of heptane to toluene) to give 9h (6.14 g, 84%) as a pale (413.52): C 75.52, H 6.58, N 10.16; found: C 75.13, H 6.29, N 10.19.
1
yellow oil. Rf ¼ 0.55 (toluene). H NMR (500 MHz, CDCl3): d ¼
2-(1-(4-((9-(4-Cyanophenoxy)nonyl)oxy)phenyl)ethylidene)malo-
7.65 (ddd, J ¼ 9.0, 6.7, 2.3 Hz, 1H), 6.78 (ddd, J ¼ 9.0, 7.0, 1.8 Hz, nonitrile (13d). White solid. Rf ¼ 0.68 (CH2Cl2). Mp ¼ 87.1–88.1
1H), 4.10 (t, J ¼ 6.6 Hz, 2H), 2.61 (d, J ¼ 5.0 Hz, 3H), 1.96–1.78 ꢀC. 1H NMR (500 MHz, CDCl3): d ¼ 7.60 (d, J ¼ 8.9 Hz, 2H), 7.57
(m, 2H), 1.52–1.41 (m, 2H), 1.37–1.25 (m, 8H), 0.88 (t, J ¼ 6.8 Hz, (d, J ¼ 8.8 Hz, 2H), 6.97 (d, J ¼ 8.9 Hz, 2H), 6.93 (d, J ¼ 8.8 Hz,
3H) ppm. 13C NMR (125 MHz, CDCl3): d ¼ 193.9 (dd, J ¼ 3.8, 2.4 2H), 4.01 (t, J ¼ 6.5 Hz, 2H), 3.99 (t, J ¼ 6.5 Hz, 2H), 2.61 (s, 3H),
Hz), 152.8 (dd, J ¼ 8.1, 3.8 Hz), 152.0 (dd, J ¼ 255.7, 11.3 Hz), 1.83–1.77 (m, 4H), 1.49–1.43 (m, 4H), 1.39–1.35 (m, 6H) ppm.
141.1 (dd, J ¼ 248.4, 15.6 Hz), 125.0 (dd, J ¼ 4.1, 3.4 Hz), 119.5 13C NMR (125 MHz, CDCl3): d ¼ 174.2, 162.8, 162.5, 134.1,
(dd, J ¼ 10.5, 2.1), 108.9 (dd, J ¼ 2.7, 1.0 Hz), 70.1, 31.9, 31.3 (d, J 130.0, 127.7, 119.5, 115.3, 115.0, 113.9, 113.6, 103.7, 81.8, 68.5,
¼ 7.2 Hz), 29.4, 29.3, 29.1, 25.9, 22.8, 14.2 ppm. HRMS (ESP +ve) 68.5, 29.6, 29.4, 29.1, 29.1, 26.1, 26.0, 23.9 ppm, 1C masked.
calcd for C16H22F2O2Na [(M + Na)+]: m/z ¼ 307.1480; exp HRMS (MALDI +ve) calcd for C27H29N3O2Na ([M + Na]+): m/z ¼
307.1483. Analysis calcd (%) for C16H22F2O2 (284.35): C 67.59, H 450.2157; exp 450.2153. Analysis calcd (%) for C27H29N3O2
7.80; found: C 67.69, H 7.71.
(427.55): C 75.85, H 6.84, N 9.83; found: C 75.50, H 6.81, N 9.80.
General procedure for 13a–i. A biphasic mixture of 9 (either
2-(1-(4-((10-(4-Cyanophenoxy)decyl)oxy)phenyl)ethylidene)malo-
a–i), malononitrile (3.5–9 molar equivalents), NH4OAc (3–10 nonitrile (13e). White solid. Rf ¼ 0.65 (CH2Cl2). Mp ¼ 62.6–63.8
molar equivalents) in toluene (100–300 mL) and AcOH (4–23 ꢀC. 1H NMR (500 MHz, CDCl3): d ¼ 7.60 (d, J ¼ 8.9 Hz, 2H), 7.57
mL) was heated using a Dean–Stark apparatus for 3–10 h. The (d, J ¼ 8.8 Hz, 2H), 6.97 (d, J ¼ 8.9 Hz, 2H), 6.93 (d, J ¼ 8.8 Hz,
vessel was cooled, diluted with toluene and decanted into 2H), 4.01 (t, J ¼ 6.5 Hz, 2H), 3.99 (t, J ¼ 6.5 Hz, 2H), 2.61 (s, 3H),
a separatory funnel and water was added. The phases were 1.83–1.77 (m, 4H), 1.47–1.43 (m, 4H), 1.37–1.31 (m, 8H) ppm. 13
C
separated and the organic phase washed with water and brine. NMR (125 MHz, CDCl3): d ¼ 174.2, 162.8, 162.5, 134.1, 130.0,
The organic phase was dried over MgSO4, ltered and the 127.7, 199.5, 115.3, 115.0, 113.9, 113.6, 103.7, 81.8, 68.5, 68.5,
solvent removed in vacuo. For subsequent purication for 29.6, 29.4, 29.1, 29.1, 26.1, 26.0, 23.9 ppm, 2Cs masked. HRMS
obtaining 13 (either a–i), see ESI.†
(MALDI +ve) calcd for C28H32N3O2 ([M + H]+): m/z ¼ 442.2489;
2-(1-(4-((5-(4-Cyanophenoxy)pentyl)oxy)phenyl)ethylidene)malo- exp 442.2491. Analysis calcd (%) for C28H31N3O2 (441.58): C,
nonitrile (13a). Yellowish solid. Rf ¼ 0.65 (CH2Cl2). Mp ¼ 83.2– 76.16; H, 7.08; N, 9.52; found: C 76.30, H 7.07, N 9.50.
84.9, 95.6–100.3 ꢀC. 1H NMR (500 MHz, CDCl3): d ¼ 7.60 (d, J ¼
2-(1-(40-(Octyloxy)-[1,10-biphenyl]-4-yl)ethylidene)malononitrile
1
ꢀ
8.9 Hz, 2H), 7.57 (d, J ¼ 8.9 Hz, 2H) 6.97 (d, J ¼ 8.9 Hz, 2H), 6.94 (13f). White solid. Rf ¼ 0.56 (toluene). Mp ¼ 58.6–59.4 C. H
(d, J ¼ 8.9 Hz, 2H), 4.06 (t, J ¼ 6.2 Hz, 2H), 4.04 (t, J ¼ 6.2 Hz, 2H), NMR (500 MHz, CDCl3): d ¼ 7.68 (d, J ¼ 8.5 Hz, 2H), 7.64 (d, J ¼
2.61 (s, 3H), 1.92–1.87 (m, 4H), 1.70–1.64 (m, 2H) ppm. 13C NMR 8.5 Hz, 2H), 7.56 (d, J ¼ 8.7 Hz, 2H), 6.99 (d, J ¼ 8.7 Hz, 2H), 4.01
(125 MHz, CDCl3): d ¼ 174.1, 162.7, 162.4, 134.1, 130.0, 127.9, (t, J ¼ 6.6 Hz, 2H), 2.67 (s, 3H), 1.84–1.78 (m, 2H), 1.51–1.45 (m,
119.4, 115.3, 115.0, 113.8, 113.5, 104.0, 82.0, 68.2, 28.9, 28.8, 2H), 1.40–1.26 (m, 8H), 0.90 (t, J ¼ 6.9 Hz, 2H) ppm. 13C NMR
23.9, 22.8 ppm, 1C masked. HRMS (MALDI +ve) calcd for (125 MHz, CDCl3): d ¼ 174.7, 159.9, 145.2, 133.8, 131.5, 128.4,
C23H22N3O2 ([M + H]+): m/z ¼ 372.1707; exp 372.1707. Analysis 128.3, 127.1, 115.2, 113.2, 83.8, 68.3, 32.0, 29.5, 29.4, 29.4, 26.2,
calcd (%) for C23H21N3O2 (371.44): C 74.37, H 5.70, N 11.31; 24.1, 22.8, 14.3 ppm. HRMS (MALDI +ve) calcd for
found: C 73.41, H 5.76, N 10.80.
2-(1-(4-((6-(4-Cyanophenoxy)hexyl)oxy)phenyl)ethylidene)malo-
C
25H28N2ONa [(M + Na)+]: m/z ¼ 395.2094; exp 395.2102.
Analysis calcd (%) for C25H28N2O (372.51): C 80.61, H 7.58, N
nonitrile (13b). White solid. Rf ¼ 0.61 (CH2Cl2). Mp ¼ 62.5–64.5 7.52; found: C 80.67, H 7.67, N 7.38.
ꢀC. 1H NMR (500 MHz, CDCl3): d ¼ 7.60 (d, J ¼ 8.9 Hz, 2H), 7.57
2-(1-(20,30-Diuoro-40-(octyloxy)-[1,10-biphenyl]-4-yl)ethylidene)
(d, J ¼ 8.9 Hz, 2H) 6.97 (d, J ¼ 8.9 Hz, 2H), 6.93 (d, J ¼ 8.9 Hz, malononitrile (13g). White solid. Rf ¼ 0.61 (toluene). Mp ¼ 59.5–
2H), 4.04 (t, J ¼ 6.4 Hz, 2H), 4.02 (t, J ¼ 6.3 Hz, 2H), 2.61 (s, 3H), 60.4 ꢀC. 1H NMR (500 MHz, CDCl3): d ¼ 7.65 (apparent s, 4H),
1.86–1.83 (m, 4H), 1.57–1.54 (m, 4H) ppm. 13C NMR (125 MHz, 7.16–7.10 (ddd, J ¼ 8.7, 8.2, 2.4, 1H), 6.83 (ddd, J ¼ 9.1, 7.5, 1.8
CDCl3): d ¼ 174.1, 162.8, 162.5, 134.1, 130.0, 127.9, 119.4, 115.3, Hz, 1H), 4.09 (t, J ¼ 6.6 Hz, 2H), 2.68 (s, 3H), 1.92–1.81 (m, 2H),
115.0, 113.8, 113.5, 103.9, 82.0, 68.3, 29.1, 29.1, 25.9, 25.9, 23.9 1.54–1.44 (m, 2H), 1.42–1.22 (m, 8H), 0.89 (t, J ¼ 6.8, 1H) ppm.
ppm, 1C masked. HRMS (MALDI +ve) calcd for C24H24N3O2 ([M 13C NMR (125 MHz, CDCl3): d ¼ 174.7, 149.1 (dd, J ¼ 250, 11.4
+ H]+): m/z ¼ 386.1858; exp 386.1864. Analysis calcd (%) for Hz), 149.0 (dd, J ¼ 8.1, 3.1 Hz), 141.9 (dd, J ¼ 248.2, 14.8 Hz),
C
24H23N3O2 (385.47): C 74.78, H 6.01, N 10.90; found: C 74.75, H 139.3, 134.9, 129.4, 129.4, 127.9, 123.8, 123.7, 123.7, 121.2,
5.73, N 10.81. 121.1, 113.1, 112.9, 109.9, 84.7, 70.1, 31.9, 29.4, 29.4, 29.3, 26.0,
2-(1-(4-((8-(4-Cyanophenoxy)octyl)oxy)phenyl)ethylidene)malononi- 24.3, 22.8, 14.2 ppm. HRMS (MALDI +ve) calcd for C25H27F2N2O
trile (13c). White solid. Rf ¼ 0.62 (CH2Cl2). Mp ¼ 67.0–67.7 ꢀC. 1H [(M + H)+]: m/z ¼ 409.2086; exp 409.2095. Analysis calcd (%) for
NMR (500 MHz, CDCl3): d ¼ 7.64 (d, J ¼ 8.9 Hz, 2H), 7.60 (d, J ¼ 8.9
C25H26F2N2O (408.49): C 73.51, H 6.42, N 6.86; found: C 73.33,
Hz, 2H) 7.00 (d, J ¼ 8.9 Hz, 2H), 6.96 (d, J ¼ 8.9 Hz, 2H), 4.05 (t, J ¼ H 6.30, N 6.78.
6.5 Hz, 2H), 4.02 (t, J ¼ 6.4 Hz, 2H), 2.64 (s, 3H), 1.87–1.81 (m, 4H),
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2-(1-(2,3-Diuoro-4-(octyloxy)phenyl)ethylidene)malononitrile
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[C7H7]BF4 (527 mg, 2.96 mmol) in CH2Cl2 (100 mL) at ꢁ78 C,
(13h). Off-white solid. Rf ¼ 0.62 (toluene); Mp ¼ 59.1–60.5 ꢀC; 1H
NMR (500 MHz, CDCl3): d ¼ 7.13 (ddd, J ¼ 9.9, 7.6, 2.2 Hz, 1H),
6.82 (ddd, J ¼ 9.9, 7.2, 1.8 Hz, 1H), 4.09 (t, J ¼ 6.5 Hz, 2H), 2.61
(d, J ¼ 1.6 Hz, 3H), 1.92–1.74 (m, 2H), 1.50–1.39 (m, 2H), 1.41–
1.19 (m, 8H), 0.94–0.76 (m, 3H) ppm. 13C NMR (125 MHz,
CDCl3): d ¼ 170.3 (dd, J ¼ 2.5, 1.5 Hz), 151.9 (dd, J ¼ 8.1, 3.7 Hz),
148.5 (dd, J ¼ 254.3, 12.1 Hz), 141.6, (dd, J ¼ 251.7, 13.8 Hz),
123.2 (dd, J ¼ 4.5, 3.2 Hz), 117.4 (d, J ¼ 10.6 Hz), 112.2, 112.1,
109.3 (dd, J ¼ 3.1, 1.3 Hz), 87.3, 70.1, 31.8, 29.2, 29.2, 28.9, 25.8,
24.1 (d, J ¼ 4.6 Hz), 22.7, 14.1 ppm; HRMS (MALDI +ve) calcd for
under an argon atmosphere, was slowly added NEt3 (1.0 mL, 7.2
mmol) and the resulting solution stirred for 30 min. The reac-
tion was quenched by addition of aqueous 1 M HCl (100 mL)
and the vessel allowed to reach ambient temperature. The
phases were separated and the organic phase dried over MgSO4,
ltered and the solvent removed under reduced pressure. The
residue was dissolved in CH2ClCH2Cl (50 mL) and to the vessel
[Ph3C]BF4 (1.00 g, 3.03 mmol) was added whereaer the mixture
was heated to reux point for 2 h. The cooled vessel was placed
in an ice bath and NEt3 (0.70 mL, 5.0 mmol) was added slowly to
the ask. Toluene (50 mL) was added to the ask and the
contents allowed to sit overnight at rt, aer which time the
solvent was removed in vacuo and the crude residue puried by
ash column chromatography (2% EtOAc/toluene) to give 3b
(603 mg, 47%), as a uffy yellow solid. Rf ¼ 0.33 (2% EtOAc/
toluene). Mp ¼ 122.1–124.0 ꢀC. 1H NMR (500 MHz, CDCl3):
d ¼ 7.67 (d, J ¼ 8.9 Hz, 2H), 7.57 (d, J ¼ 8.9 Hz, 2H), 6.96 (d, J ¼
8.9 Hz, 2H), 6.93 (d, J ¼ 8.9 Hz, 2H), 6.75 (s, 1H), 6.55 (dd, J ¼
11.3, 6.4 Hz, 1H), 6.44 (dd, J ¼ 11.3, 6.1 Hz, 1H), 6.31–6.28 (m,
2H), 5.81 (dd, J ¼ 10.2, 3.9 Hz, 1H), 4.03 (t, J ¼ 6.4 Hz, 2H), 4.02
(t, J ¼ 6.4 Hz, 2H), 3.77 (ddd, J ¼ 3.9, 2.0, 2.0 Hz, 1H), 1.88–1.82
(m, 3H), 1.57–1.54 (m, 3H) ppm. 13C NMR (125 MHz, CDCl3): d ¼
162.5, 160.6, 140.1, 139.2, 134.1, 131.1, 130.5, 130.2, 128.0,
127.8, 123.1, 120.1, 119.4, 119.4, 115.3, 115.3, 113.0, 68.3, 68.1,
51.3, 45.4, 29.2, 29.1, 25.9, 25.9 ppm, 1C masked. HRMS (MALDI
+ve) calcd for C31H28N3O2 ([M + H]+): m/z ¼ 474.2176; exp
474.2176. Analysis calcd (%) for C31H27N3O2 (473.58): C 78.62, H
5.75, N 8.87; found: C 78.31, H 5.42, N 8.69.
C
19H22F2N2ONa [(M + Na)+]: m/z: 355.1592, found m/z ¼
355.1600.
2-(1-(4-Octylphenyl)ethylidene)malononitrile (13i). White solid.
Rf ¼ 0.65 (toluene). Mp ¼ 51.5–52.0 ꢀC. 1H NMR (500 MHz,
CDCl3): d ¼ 7.50 (d, J ¼ 8.3 Hz, 2H), 7.30 (d, J ¼ 8.3 Hz, 2H), 2.66
(t, J ¼ 7.7 Hz, 2H), 2.63 (s, 3H), 1.66–1.1.60 (m, 2H), 1.35–1.27
(m, 10H), 0.88 (t, J ¼ 7.1 Hz, 3H) ppm. 13C NMR (125 MHz,
CDCl3): d ¼ 175.3, 148.5, 133.3, 129.3, 127.7, 113.3, 113.2, 83.7,
36.1, 32.0, 31.2, 29.5, 29.4, 29.3, 24.2, 22.8, 14.2 ppm. HRMS
(MALDI +ve) calcd for C19H24N2Na ([M + Na]+): m/z ¼ 303.1831;
exp 303.1838. Analysis calcd (%) for C19H24N2 (280.42): C 81.38,
H 8.63, N 9.99; found: C 81.60, H 8.62, N 10.05.
2-(4-((5-(4-Cyanophenoxy)pentyl)oxy)phenyl)azulene-1,1(8aH)-
dicarbonitrile (3a). To a solution of 13a (882 mg, 2.37 mmol)
and [C7H7]BF4 (483 mg, 2.71 mmol) in CH2Cl2 (100 mL) at ꢁ78
ꢀC, under an argon atmosphere, was slowly added NEt3 (0.70
mL, 5.0 mmol) and the resulting solution stirred for 30 min.
The reaction was quenched by addition of aqueous 1 M HCl
(100 mL) and the vessel allowed to reach ambient temperature.
The phases were separated and the organic phase dried over
MgSO4, ltered and the solvent removed under reduced pres-
sure. The residue was dissolved in CH2ClCH2Cl (50 mL) and to
the vessel [Ph3C]BF4 (882 mg, 2.49 mmol) was added whereaer
the mixture was heated to reux point for 2 h. The cooled vessel
was placed in an ice bath and NEt3 (0.50 mL, 3.6 mmol) was
added slowly to the ask. Toluene (50 mL) was added to the
ask and the contents allowed to sit overnight at rt, aer which
time the solvent was removed in vacuo and the crude residue
puried by ash column chromatography (2% EtOAc/toluene)
to give 3a (345 mg, 32%), as an orange solid. Rf ¼ 0.30 (2%
EtOAc/toluene). Mp ¼ 141.0–145.2 ꢀC. 1H NMR (500 MHz,
CDCl3): d ¼ 7.70 (d, J ¼ 8.9 Hz, 2H), 7.61 (d, J ¼ 8.9 Hz, 2H), 6.99
(d, J ¼ 8.9 Hz, 2H); 6.97 (d, J ¼ 8.9 Hz, 2H), 6.79 (s, 1H), 6.59 (dd,
J ¼ 11.3, 6.4 Hz, 1H), 6.47 (dd, J ¼ 11.3, 6.1 Hz, 1H), 6.34–6.31
(m, 2H), 5.84 (dd, J ¼ 10.2, 3.9 Hz, 1H), 4.08 (t, J ¼ 6.3 Hz, 2H),
4.07 (t, J ¼ 6.3 Hz, 2H), 3.80 (ddd, J ¼ 3.9, 1.9, 1.9 Hz, 1H), 1.96–
1.89 (m, 4H), 1.74–1.69 (m, 2H) ppm. 13C NMR (125 MHz,
CDCl3): d ¼ 162.3, 160.4, 139.9, 139.0, 134.0, 131.0, 130.4,
130.1, 127.8, 127.6, 123.0, 120.0, 119.4, 119.3, 115.3, 115.2,
115.1, 112.9, 103.7, 68.1, 67.8, 51.1, 45.2, 28.8, 28.8, 22.7 ppm.
HRMS (MALDI +ve) calcd for C30H26N3O2 ([M + H]+): m/z ¼
460.2020; exp 460.2021. Analysis calcd (%) for C30H25N3O2
(459.55): C 78.41, H 5.48, N 9.14; found: C 78.11, H 5.40, N 9.05.
2-(4-((6-(4-Cyanophenoxy)hexyl)oxy)phenyl)azulene-1,1(8aH)-
dicarbonitrile (3b). To a solution of 13b (1.05 g, 2.72 mmol) and
2-(4-((8-(4-Cyanophenoxy)octyl)oxy)phenyl)azulene-1,1(8aH)-
dicarbonitrile (3c). To a solution of 13c (1.04 g, 2.52 mmol) and
[C7H7]BF4 (522 mg, 2.93 mmol) in CH2Cl2 (100 mL) at ꢁ78 ꢀC,
under an argon atmosphere, was slowly added NEt3 (1.0 mL,
7.2 mmol) and the resulting solution stirred for 30 min. The
reaction was quenched by addition of aqueous 1 M HCl (100
mL) and the vessel allowed to reach ambient temperature.
The phases were separated and the organic phase dried over
MgSO4, ltered and the solvent removed under reduced
pressure. The residue was dissolved in CH2ClCH2Cl (50 mL)
and to the vessel [Ph3C]BF4 (929 mg, 2.81 mmol) was added
whereaer the mixture was heated to reux point for 2 h. The
cooled vessel was placed in an ice bath and NEt3 (0.70 mL, 5.0
mmol) was added slowly to the ask. Toluene (50 mL) was
added to the ask and the contents allowed to sit overnight at
rt, aer which time the solvent was removed in vacuo and the
crude residue puried by ash column chromatography (2%
EtOAc/toluene) to give 3c (200 mg, 16%) as an orange solid. Rf
¼ 0.35 (2% EtOAc/toluene). Mp ¼ 98.5–101.2 ꢀC. 1H NMR (500
MHz, CDCl3): d ¼ 7.67 (d, J ¼ 8.9 Hz, 2H), 7.57 (d, J ¼ 8.9 Hz,
2H), 6.96 (d, J ¼ 8.9 Hz, 2H), 6.93 (d, J ¼ 8.9 Hz, 2H), 6.75 (s,
1H), 6.55 (dd, J ¼ 11.2, 6.4 Hz, 1H), 6.44 (dd, J ¼ 11.3, 6.1 Hz,
1H), 6.31–6.28 (m, 2H), 5.81 (dd, J ¼ 10.2, 3.8 Hz, 1H), 4.01 (t, J
¼ 6.5 Hz, 1H), 4.00 (d, J ¼ 6.5 Hz, 1H), 3.77 (ddd, J ¼ 3.9, 2.0,
2.0 Hz, 1H), 1.84–1.78 (m, 4H), 1.51–1.45 (m, 4H), 1.42–1.39
(m, 4H) ppm. 13C NMR (125 MHz, CDCl3): d ¼ 162.6, 160.7,
140.2, 139.2, 134.1, 131.1, 130.4, 130.2, 127.9, 127.8, 123.0,
120.0, 119.5, 119.4, 115.5, 115.3, 113.0, 103.8, 68.5, 68.3, 51.3,
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45.4, 29.4, 29.2, 29.1, 26.1, 26.0 ppm, 2C masked. HRMS J ¼ 11.3, 6.3 Hz, 1H), 6.44 (dd, J ¼ 11.3, 6.1 Hz, 1H), 6.31–6.28
(MALDI +ve) calcd for C33H32N3O2 ([M + H]+): m/z ¼ 502.2489; (m, 2H), 5.81 (dd, J ¼ 10.2, 3.8 Hz, 1H), 4.01 (d, J ¼ 6.6 Hz, 2H),
exp 502.2490.
3.99 (d, J ¼ 6.6 Hz, 2H), 3.77 (ddd, J ¼ 3.8, 1.9, 1.9 Hz, 1H), 1.83–
2-(4-((9-(4-Cyanophenoxy)nonyl)oxy)phenyl)azulene-1,1(8aH)- 1.77 (m, 4H), 1.49–1.43 (m, 4H), 1.39–1.32 (m, 6H) ppm. 13C
dicarbonitrile (3d). To a solution of 13d (1.02 g, 2.39 mmol) and NMR (125 MHz, CDCl3): d ¼ 162.6, 160.7, 140.2, 139.2, 134.1,
[C7H7]BF4 (500 mg, 2.81 mmol) in CH2Cl2 (100 mL) at ꢁ78 ꢀC, 131.1, 130.4, 130.1, 127.9, 127.8, 123.0, 120.0, 119.5, 119.4,
under an argon atmosphere, was slowly added NEt3 (1.0 mL, 115.5, 115.3, 115.3, 113.0, 103.8, 68.5, 68.3, 51.3, 45.4, 29.6,
7.2 mmol) and the resulting solution stirred for 30 min. The 29.6, 29.5, 29.5, 29.2, 29.1, 26.1, 26.1 ppm. HRMS (MALDI +ve)
reaction was quenched by addition of aqueous 1 M HCl (100 calcd for C35H36N3O2 ([M + H]+): m/z ¼ 530.2802; exp 530.2806.
mL) and the vessel allowed to reach ambient temperature. The
2-(40-(Octyloxy)-[1,10-biphenyl]-4-yl)azulene-1,1(8aH)-dicarboni-
phases were separated and the organic phase dried over trile (3f). Method 1: to a solution/suspension of the crude
MgSO4, ltered and the solvent removed under reduced pres- mixture from 13f (3.54 g, 9.50 mmol) and [C7H7]BF4 (1.71 g, 9.61
sure. The residue was dissolved in CH2ClCH2Cl (50 mL) and to mmol) in CH2Cl2 (250 mL), at ꢁ78 ꢀC under an argon atmo-
the vessel [Ph3C]BF4 (935 mg, 2.83 mmol) was added where- sphere, was added NEt3 (1.0 g, 1.4 mL, 10 mmol) over a 30 min
aer the mixture was heated to reux point for 2 h. The cooled period and the reaction mixture stirred at ꢁ78 ꢀC for 2 h.
vessel was placed in an ice bath and NEt3 (0.70 mL, 5.0 mmol) Additional NEt3 was added (0.5 mL, 3.58 mmol) and the reac-
was added slowly to the ask. Toluene (50 mL) was added to tion mixture was le to stir for 1 h and allowed to reach rt and
the ask and the contents allowed to sit overnight at rt, aer subjected to ultrasonication. HCl (150 mL, 2 M) was added to
which time the solvent was removed in vacuo and the crude the vessel and the phases separated. The aqueous phase was
residue puried by ash column chromatography (2% EtOAc/ extracted with CH2Cl2 (100 mL) and the combined organic
toluene) to give 3d (258 mg, 21%) as an orange solid. Rf ¼ 0.36 phases dried over MgSO4, ltered, and the solvent was removed
(2% EtOAc/toluene). Mp ¼ 98.9–103.8, 125.6–130.6 ꢀC. 1H in vacuo. The residue was taken up in CH2ClCH2Cl (125 mL) and
NMR (500 MHz, CDCl3): d 7.67 (d, J ¼ 8.8 Hz, 2H), 7.57 (d, J ¼ treated with [Ph3C]BF4 (3.85 g, 11.6 mmol) and subjected to
8.8 Hz, 2H), 6.96 (d, J ¼ 8.8 Hz, 2H), 6.93 (d, J ¼ 8.8 Hz, 2H), reux for 2 h under inert atmosphere. The reaction mixture was
6.75 (s, 1H), 6.55 (dd, J ¼ 11.2, 6.4 Hz, 1H), 6.44 (dd, J ¼ 11.2, diluted with toluene (125 mL) and cooled to 0 ꢀC and NEt3 (1.2 g,
6.1 Hz, 1H), 6.31–6.28 (m, 2H), 5.81 (dd, J ¼ 10.2, 3.8 Hz, 1H), 1.7 mL, 12 mmol) was added, where the mixture was stirred
4.01 (t, J ¼ 6.8 Hz, 2H), 4.00 (t, J ¼ 6.8 Hz, 2H), 3.77 (ddd, J ¼ overnight and allowed to reach room temperature. The solvent
3.8, 2.0, 2.0 Hz, 1H), 1.83–1.78 (m, 4H), 1.49–1.44 (m, 4H), was removed in vacuum, and the residue was subjected to ash
1.40–1.37 (m, 6H) ppm. 13C NMR (125 MHz, CDCl3): d ¼ 162.6, chromatography (40–50% CH2Cl2/heptane) and crystallized
160.7, 140.2, 139.2, 134.1, 131.1, 130.4, 130.2, 127.9, 127.8, from CH2Cl2/ethanol to furnish 3f (502 mg, 11%) as a yellow
123.0, 120.0, 119.5, 119.4, 115.5, 115.3, 113.0, 103.8, 68.5, 68.3, solid. Method 2: To a degassed solution of 15 (1.54 g, 4.03 mmol)
51.3, 45.4, 29.6, 29.4, 29.2, 29.1, 26.1, 26.1 ppm, 2Cs masked. in toluene (60 mL) and water (15 mL) was added Pd(OAc)2 (55
HRMS (MALDI +ve) calcd for C34H34N3O2 ([M + H]+): m/z ¼ mg, 0.245 mmol), RuPhos (187 mg, 0.400 mmol), K3PO4 (1.31 g,
516.2646; exp 516.2649. Analysis calcd (%) for C34H33N3O2 6.17 mmol) and 11f (1.56 g, 6.24 mmol), and the biphasic
ꢀ
(515.66): C 79.19, H 6.45, N 8.15; found: C 78.68, H 6.18, N mixture stirred for 18 h at 80 C. TLC indicated an incomplete
8.11.
reaction and more Pd(OAc)2 (60 mg, 0.267 mmol), RuPhos (195
2-(4-((10-(4-Cyanophenoxy)decyl)oxy)phenyl)azulene-1,1(8aH)- mg, 0.419 mmol) and K3PO4 (2.32 g, 10.9 mmol) and 11f (1.21 g,
dicarbonitrile (3e). To a solution of 13e (1.12 g, 2.54 mmol) and mmol) were added and the mixture heated to 80 ꢀC for another
[C7H7]BF4 (503 mg, 2.83 mmol) in CH2Cl2 (100 mL) at ꢁ78 ꢀC, 18 h. The contents of the vessel were diluted with water (100
under an argon atmosphere, was slowly added NEt3 (1.0 mL, mL) and the phases were separated. The aqueous phase was
7.2 mmol) and the resulting solution stirred for 30 min. The extracted with CH2Cl2 (100 mL) and the combined organic
reaction was quenched by addition of aqueous 1 M HCl (100 extracts were dried over MgSO4, ltered and the solvent
mL) and the vessel allowed to reach ambient temperature. The removed in vacuo. The crude residue was subjected to ash
phases were separated and the organic phase dried over column chromatography (gradient elution of 55–70% toluene/
MgSO4, ltered and the solvent removed under reduced pres- heptane) and subsequently recrystallized from CH2Cl2/
sure. The residue was dissolved in CH2ClCH2Cl (50 mL) and to heptane to give pure 3f (562 mg, 30%). Rf ¼ 0.42 (50% CH2Cl2/
1
the vessel [Ph3C]BF4 (851 mg, 2.58 mmol) was added where- heptane). Mp ¼ Cr 90.6 (N 75.7) Iso; Iso 75.6 N 29.8 Tg ꢀC. H
aer the mixture was heated to reux point for 2 h. The cooled NMR (500 MHz, CDCl3): d ¼ 7.78 (d, J ¼ 8.3 Hz, 2H), 7.66 (d, J ¼
vessel was placed in an ice bath and NEt3 (0.70 mL, 5.0 mmol) 8.3 Hz, 2H), 7.56 (d, J ¼ 8.7 Hz, 2H), 6.99 (d, J ¼ 8.7 Hz, 2H), 6.91
was added slowly to the ask. Toluene (50 mL) was added to the (s, 1H), 6.57 (dd, J ¼ 11.2, 6.4 Hz, 1H), 6.47 (dd, J ¼ 11.2, 6.1 Hz,
ask and the contents allowed to sit overnight at rt, aer which 1H), 6.35 (d, J ¼ 6.4 Hz, 1H), 6.31 (ddd, J ¼ 10.1, 6.1, 2.1 Hz, 1H),
time the solvent was removed in vacuo and the crude residue 5.84 (dd, J ¼ 10.1, 3.8 Hz, 1H), 4.01 (t, J ¼ 6.6 Hz, 1H), 3.81 (ddd,
puried by ash column chromatography (2% EtOAc/toluene) J ¼ 3.7, 2.0, 2.0 Hz, 1H), 1.84–1.78 (m, 2H), 1.51–1.46 (m, 2H),
to give 3e (552 mg, 41%), as an orange solid. Rf ¼ 0.38 (2% 1.43–1.14 (m, 10H), 0.89 (t, J ¼ 6.9 Hz, 2H) ppm. 13C NMR (125
EtOAc/toluene). Mp ¼ 102.2–121.8 ꢀC. 1H NMR (500 MHz, MHz, CDCl3): d ¼ 159.3, 142.4, 140.0, 138.9, 132.0, 131.7, 131.0,
CDCl3): d ¼ 7.67 (d, J ¼ 8.9 Hz, 2H), 7.57 (d, J ¼ 8.9 Hz, 2H), 6.97 130.8, 128.5, 128.1, 127.7, 127.2, 126.7, 120.7, 119.5, 115.2,
(d, J ¼ 8.9 Hz, 2H), 6.93 (d, J ¼ 8.9 Hz, 2H), 6.75 (s, 1H), 6.55 (dd, 115.0, 112.8, 68.2, 51.2, 45.1, 31.8, 29.4, 29.3, 29.3, 26.1, 22.7,
89740 | RSC Adv., 2015, 5, 89731–89744
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14.1 ppm. HRMS (MALDI +ve) calcd for C32H32N2ONa [(M + m/z ¼ 519.2217. Analysis calcd (%) for C32H30F2N2O (496.60): C
Na)+]: m/z ¼ 483.2407; exp 483.2406. Analysis calcd (%) for 77.40, H 6.09, N 5.64; found: C 77.59, H 5.88, N 5.70.
C
32H32N2O (460.62): C 83.44, H 7.00, N 6.08; found: C 83.28, H
2-(2,3-Diuoro-4-(octyloxy)phenyl)azulene-1,1(8aH)-dicarboni-
trile (3h). To a mixture of 13h (6.58 g, 19.8 mmol) and [C7H7]BF4
6.90, N 6.12.
2-(20,30-Diuoro-40-(octyloxy)-[1,10-biphenyl]-4-yl)azulene-1,1(8aH)- (3.62 g, 20.4 mmol) in CH2Cl2 (250 mL) at ꢁ78 ꢀC under an
dicarbonitrile (3g). Method 1: to a mixture of 13g (3.35 g, 8.21 mmol) argon atmosphere, was added NEt3 (2.8 mL, 20ꢀ.4 mmol) over 30
and [C7H7]BF4 (1.53 g, 8.60 mmol) in CH2Cl2 (250 mL) at ꢁ78 ꢀC min, and the reaction mixture stirred at ꢁ78 C for 2 h. Addi-
under argon atmosphere was added NEt3 (1.2 mL, 8.6 mmol) tional NEt3 (0.5 mL, 3.58 mmol) was added and the reaction
portion-wise over 30 min and the reaction mixture stirred at ꢁ78 mixture was allowed to stir for a further 60 min. The reaction
ꢀC for 2 h. Since there were still starting material and tropylium le was quenched cold with HCl (50 mL, 2 M) and allowed to reach
unreacted, more NEt3 was added (0.5 mL, 3.58 mmol) and the rt and diluted with water (50 mL). The phases were separated
reaction mixture was le to stir for 1 h more and allowed to reach rt and the organic phase was washed with water (250 mL), dried
while being sonicated. Then it was quenched with HCl (100 mL, 2 over MgSO4, ltered and the solvent removed under reduced
M) and diluted with water (50 mL). Subsequently, the phases were pressure. The residue was taken up in CH2ClCH2Cl (125 mL)
separated and the water phase was extracted with CH2Cl2 (100 mL) and treated with [Ph3C]BF4 (7.96 g, 24.1 mmol) and the vessel
and the combined organic phase was dried over MgSO4 and the subjected to reux for 2 h under argon. The reaction mixture
solvent was removed by rotary evaporation. The residue was was cooled to 0 ꢀC and diluted with toluene (125 mL) and NEt3
treated with [Ph3C]BF4 (3.27 g, 9.89 mmol) in DCE (125 mL) under (3.4 mL, 24.4 mmol) was added. The mixture was stirred over-
reux for 2 h under an argon atmosphere, aer which time the night, allowing the vessel to reach rt. The solvent was removed
reaction mixture was cooled to 0 ꢀC and diluted with toluene (125 in vacuo and the residue was subjected to ash chromatog-
ꢀ
mL). When the reaction mixture reached 0 C, NEt3 (1.5 mL, 10 raphy (30–50% CH2Cl2/heptane) to give 3h (2.528 g, 30%) as
mmol) was added, and the mixture was stirred overnight, while a yellow solid. Rf ¼ 0.60 (50% CH2Cl2/heptane). Mp ¼ 95.0–97.9
allowing to reach rt, and le to stir for 15 h. The solvent was ꢀC. 1H NMR (500 MHz, CDCl3): d ¼ 7.52 (td, J ¼ 8.5, 2.0 Hz, 1H),
removed in vacuo and the residue was subjected to ash column 7.04 (s, 1H), 6.92–6.81 (m, 1H), 6.57 (dd, J ¼ 11.3, 6.4 Hz, 1H),
chromatography (40–50% CH2Cl2/heptane) and crystallized from 6.48 (dd, J ¼ 11.3, 6.1 Hz, 1H), 6.37 (d, J ¼ 6.4 Hz, 1H), 6.31
CH2Cl2 and ethanol to give 3g (1.104 g, 25%) as a yellow solid. (ddd, J ¼ 10.3, 6.1, 1.9 Hz, 1H), 5.80 (dd, J ¼ 10.3, 3.8 Hz, 1H),
Method 2: To a degassed solution of 15 (2.05 g, 5.36 mmol) in 4.10 (t, J ¼ 6.6 Hz, 2H), 3.74 (ddd, J ¼ 3.8, 1.9, 1.9 Hz, 1H), 1.88–
toluene (60 mL) and water (15 mL) were added Pd(OAc)2 (76 mg, 1.82 (m, 2H), 1.51–1.45 (m, 2H), 1.40–1.25 (m, 8H), 0.90 (t, J ¼
0.339 mmol), RuPhos (262 mg, 0.561 mmol) and K3PO4 (2.51 g, 6.8 Hz, 3H) ppm. 13C NMR (125 MHz, CDCl3): d ¼ 150.51 (dd, J
11.8 mmol) and 11g (1.56 g, mmol). Degassed water (15ꢀmL) was ¼ 254.2, 11.8 Hz), 149.89 (dd, J ¼ 8.2, 3.6 Hz), 142.05 (dd, J ¼
added and the biphasic mixture stirred for 18 h at 90 C. Addi- 249.0, 14.8 Hz), 139.27, 135.90 (d, J ¼ 14.9 Hz), 132.86 (dd. J ¼
tional Pd(OAc)2 (62 mg, 0.276 mmol), RuPhos (206 mg, 0.441 4.3, 3.3 Hz), 131.08 (d, J ¼ 1.6 Hz), 127.91, 121.71 (dd, J ¼ 4.3,
mmol) and K3PO4 (1.80 g, 8.48 mmol) and 11g (1.04 g, mmol) were 3.6 Hz), 121.67, 119.45, 115.22, 112.95 (d, J ¼ 9.1 Hz), 112.83,
added and the mixture heated to 80 ꢀC for a further 18 h. The 109.34 (dd, J ¼ 3.0, 1.2 Hz), 70.03, 50.36, 46.32, 31.91, 29.38,
contents of the vessel were diluted with water (100 mL) and the 29.31, 29.09, 25.95, 22.78, 14.22 ppm, 1C masked. HRMS
phases were separated. The aqueous phase was extracted with (MALDI +ve) calcd for C26H26F2N2O [(M)+]: m/z ¼ 420.2008; exp
CH2Cl2 (100 mL) and the combined organic components were 420.2008; analysis calcd (%) for C26H26F2N2O (420.20): C 74.26,
dried over MgSO4, ltered and the solvent removed in vacuo. The H 6.23, N 6.66; found: C 74.14, H 6.35, N 6.54.
crude residue was subjected to ash column chromatography
2-(4-Octylphenyl)azulene-1,1-(8aH)-dicarbonitrile
(3i).
To
(20% EtOAc/heptane) and a second ash column (gradient eluent a mixture of 13i (10.01 g, 35.70 mmol) and [C7H7]BF4 (6.35 g,
40–60% CH2Cl2/heptane) and then recrystallized from CH2Cl2/ 35.7 mmol) in CH2Cl2 (250 mL), at ꢁ78 ꢀC under an argon
heptane to give 3g (522 mg, 20%). Rf ¼ 0.44 (50% CH2Cl2/heptane). atmosphere, was added NEt3 (5 mL, 35.9 mmol) over 30 min,
Mp ¼ Cr 79.9 (N 52.6) Iso; Iso 52.6 N 30.8 Tg ꢀC. 1H NMR (500 MHz, and the resulting mixture allowed to stir at ꢁ78 ꢀC for 2 h.
CDCl3): d ¼ 7.80 (d, J ¼ 8.4 Hz, 2H), 7.62 (dd, J ¼ 8.4, 1.3 Hz, 2H), Saturated aqueous NH4Cl (100 mL) and water (100 mL) were
7.13 (td, J ¼ 8.5, 2.3 Hz, 1H), 6.93 (s, 1H), 6.83 (td, J ¼ 8.5, 1.6 Hz, added to the vessel and the contents allowed to reach ambient
1H), 6.58 (dd, J ¼ 11.2, 6.3 Hz, 1H), 6.49 (dd, J ¼ 11.2, 6.1 Hz, 1H), temperature. The phases were separated and the organic phase
6.37 (d, J ¼ 6.3 Hz, 0H), 6.32 (ddd, J ¼ 10.2, 6.1, 2.1 Hz, 1H), 5.84 was washed with water (200 mL) and brine (200 mL). The
(dd, J ¼ 10.2, 3.8 Hz, 1H), 4.09 (t, J ¼ 6.6 Hz, 2H), 3.81 (ddd, J ¼ 3.8, organic phase was dried over MgSO4, ltered, and the removal
2.1, 2.1 Hz, 1H), 1.85 (p, J ¼ 6.6 Hz, 2H), 1.52–1.49 (m, 2H), 1.41– of the solvent gave the crude mixture (13.08 g). Of this crude
1.20 (m, 10H), 0.89 (t, J ¼ 6.6 Hz, 3H) ppm. 13C NMR (125 MHz, material (12.84 g, 34.65 mmol) was dissolved in ClCH2CH2Cl
CDCl3): d ¼ 149.2 (dd, J ¼ 250.6, 11.2 Hz), 148.6 (dd, J ¼ 8.2, 3.0 (200 mL) and treated with [Ph3C]BF4 (13.73 g, 41.58 mmol),
Hz), 142.0 (dd, J ¼ 247.9, 14.9 Hz), 139.8, 138.8, 136.8 (dd, J ¼ 2.4, whilst being subjected to reux for 2 h under argon. Aer
1.5 Hz), 132.6, 131.1 (d, J ¼ 8.5 Hz), 129.7, 129.6 (d, J ¼ 3.3 Hz), cooling the vessel, toluene (200 mL) was added and the vessel
127.8, 126.5, 123.6 (apparent t, J ¼ 4.1 Hz), 121.7 (d, J ¼ 10.6 Hz), placed in an ice bath, where NEt3 (6.3 mL, 45 mmol) was added
121.3, 119.6, 115.4, 112.9, 109.8 (dd, J ¼ 3.3, 1.2 Hz), 70.1, 51.3, and the mixture was stirred overnight, whilst being allowed to
45.3, 32.0, 29.5, 29.4, 29.3, 26.0, 22.8, 14.3 ppm. HRMS (MALDI reach rt. Aqueous NH4Cl (100 mL) was added to the vessel and
+ve) calcd for C32H30F2N2ONa [(M + Na)+]: m/z ¼ 519.2218, found the phases separated. The organic phase was washed with water
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(100 mL) and brine (100 mL), dried with MgSO4, ltered and 26.8, 26.0 ppm. HRMS (ESP +ve) calcd for C16H22N4ONa ([M +
absorbed onto Celite. The material was puried by dry column Na]+): m/z ¼ 309.1687; exp 309.1686.
vacuum chromatography (gradient elution from heptane to
4-((10-Azidodecyl)oxy)benzonitrile (14e). Rf ¼ 0.49. Mp ¼ 46.7–
toluene in 10% steps) followed by recrystallization from boiling 47.7 ꢀC. 1H NMR (500 MHz, CDCl3): d ¼ 7.57 (d, J ¼ 8.9 Hz, 2H),
ethanol to give 3i (1.73 g, 14%). The material was stored in the 6.93 (d, J ¼ 8.9 Hz, 2H), 3.99 (t, J ¼ 6.6 Hz, 2H), 3.26 (t, J ¼ 6.9 Hz,
freezer, as it decomposes at ambient temperature. Rf ¼ 0.65 2H), 1.80 (p, J ¼ 6.6 Hz, 2H), 1.60 (p, J ¼ 6.9 Hz, 2H), 1.48–1.31
(50% toluene/heptane). Mp ¼ 54.4–58.6 ꢀC. 1H NMR (500 MHz, (m, 12H) ppm. 13C NMR (125 MHz, CDCl3): d ¼ 162.4, 134.0,
CDCl3): d ¼ 7.58 (d, J ¼ 8.4 Hz, 2H), 7.20 (d, J ¼ 8.4 Hz, 2H), 6.77 119.3, 115.2, 103.7, 68.4, 51.5, 29.4, 29.4, 29.3, 29.1, 29.0, 28.8,
(s, 1H), 6.49 (dd, J ¼ 11.2, 6.4 Hz, 1H), 6.39 (dd, J ¼ 11.2, 6.1 Hz, 26.7, 25.9 ppm. HRMS (ESP +ve) calcd for C17H24N4ONa ([M +
1H), 6.31–6.05 (m, 2H), 5.75 (dd, J ¼ 10.3, 3.8 Hz, 1H), 3.71 (ddd, Na]+): m/z ¼ 323.1842; exp 323.1842.
J ¼ 3.8, 1.9, 1.9 Hz, 1H), 2.57 (t, J ¼ 7.7 Hz, 2H), 1.62–1.52 (m,
1,1-Dicyano-2-(4-(1-(5-(4-cyanophenoxy)pentyl)-1H-1,2,3-triazol-
2H), 1.34–1.01 (m, 10H), 0.81 (t, J ¼ 7.0 Hz, 3H) ppm. 13C NMR 4-yl)phenyl)-1,8a-dihydroazulene (4a). To a degassed solution of
¨
(125 MHz, CDCl3): d ¼ 145.7, 140.5, 139.1, 131.4, 131.1, 130.7, 15 (51 mg, 0.182 mmol), 14a (96 mg, 0.417 mmol) and Hunig's
129.5, 128.0, 127.8, 126.3, 120.6, 119.6, 115.4, 113.0, 51.3, 45.3, base (10 drops) in toluene (4 mL) was added CuI (8 mg, 0.021
36.0, 32.0, 31.3, 29.6, 29.5, 29.4, 22.8, 14.3 ppm. HRMS (MALDI mmol) and the contents stirred for 2 days at rt. The solvent was
+ve) calcd for C26H27N2 [(M ꢁ H)+]: m/z ¼ 367.2169; exp removed under reduced pressure and the residue puried by
367.2169; analysis calcd (%) for C26H28N2 (368.52): C 84.74, H ash column chromatography (10% EtOAc/CH2Cl2) to furnish
7.66, N 7.60; found: C 84.69, H 7.58, N 7.60.
4a as a yellow solid (91 mg, 98%). Rf ¼ 0.60 (5% EtOAc/CH2Cl2).
General procedure for 14a–e. To a solution of 7 (either a–e) in Mp ¼ 183.6–185.5; 186.9–188.7 ꢀC. 1H NMR (500 MHz, CDCl3):
DMSO (20 mL), under an argon atmosphere, was added NaN3 d ¼ 7.92 (d, J ¼ 8.4 Hz, 2H), 7.82 (s, 1H), 7.80 (d, J ¼ 8.4 Hz, 2H),
(1.5–2 molar equivalents) and the contents of the reaction vessel 7.56 (d, J ¼ 8.8 Hz, 2H), 6.93 (s, 1H), 6.90 (d, J ¼ 8.8 Hz, 2H),
ꢀ
were heated to 50 C for 2 h. The cooled reaction mixture was 6.57 (dd, J ¼ 11.3, 6.4 Hz, 1H), 6.48 (dd, J ¼ 11.3, 6.1 Hz, 1H),
poured into ice-water (ca. 50 g) and extracted with Et2O (3 ꢂ 75 6.36 (d, J ¼ 6.4 Hz, 1H), 6.31 (ddd, J ¼ 10.2, 6.1, 1.9 Hz, 1H),
mL). The combined organics were washed with water (100 mL), 5.82 (dd, J ¼ 10.2, 3.7 Hz, 1H), 4.46 (t, J ¼ 7.0 Hz, 2H), 3.99 (t,
dried over MgSO4, ltered and the volatiles removed in vacuo. J ¼ 6.2 Hz, 2H), 3.80 (ddd, J ¼ 3.7, 1.9, 1.9 Hz, 1H), 2.06 (p, J ¼
Purication by ash column chromatography (1% EtOAc/ 7.0 Hz, 2H), 1.87 (p, J ¼ 6.2 Hz, 2H), 1.59–1.53 (m, 2H) ppm. 13
C
toluene) gave 14 (either a–e) as a white solid.
NMR (125 MHz, CDCl3): d ¼ 162.3, 146.9, 139.7, 138.8, 134.1,
4-((5-Azidopentyl)oxy)benzonitrile (14a). Rf ¼ 0.41. Mp ¼ 29.1– 132.5, 132.2, 131.1, 131.1, 130.2, 127.8, 126.9, 126.4, 121.3,
30.5 ꢀC. 1H NMR (500 MHz, CDCl3): d ¼ 7.57 (d, J ¼ 7.6 Hz, 2H), 120.2, 119.5, 119.4, 115.3, 112.9, 104.1, 51.2, 50.4, 45.2, 30.1,
6.93 (d, J ¼ 7.6 Hz, 2H), 4.01 (t, J ¼ 6.3 Hz, 2H), 3.32 (t, J ¼ 6.7 Hz, 28.5, 23.2 ppm. HRMS (MALDI +ve) calcd for C32H27N6O ([M +
2H), 1.84 (p, J ¼ 6.3 Hz, 2H), 1.68 (p, J ¼ 6.7 Hz, 2H), 1.65–1.51 H]+): m/z ¼ 511.2244; exp 511.2244. Analysis calcd (%) for
(m, 2H) ppm. 13C NMR (125 MHz, CDCl3): d ¼ 162.4, 134.1,
C32H26N6O (510.60): C 75.27, H 5.13, N 16.46; found: C 75.27,
119.4, 115.3, 104.0, 68.1, 51.4, 28.7, 28.7, 23.5 ppm. HRMS (ESP H 4.78, N 16.26.
+ve) calcd for C12H14N4ONa ([M + Na]+): m/z ¼ 231.1060; exp
1,1-Dicyano-2-(4-(1-(6-(4-cyanophenoxy)hexyl)-1H-1,2,3-triazol-
4-yl)phenyl)-1,8a-dihydroazulene (4b). To a degassed solution of
253.1060.
4-((6-Azidohexyl)oxy)benzonitrile (14b). Rf ¼ 0.42. Mp ¼ 37.4– 15 (104 mg, 0.371 mmol), 14b (117 mg, 0.478 mmol) and
1
40.5 ꢀC. H NMR (500 MHz, CDCl3): d ¼ 7.57 (d, J ¼ 8.8 Hz, 2H), Hunig's base (10 drops) in toluene (4 mL) was added CuI (10
¨
6.93 (d, J ¼ 8.8 Hz, 2H), 4.00 (t, J ¼ 6.4 Hz, 2H), 3.29 (t, J ¼ 6.8 Hz, mg, 0.053 mmol) and the contents stirred for 2 days at rt. The
2H), 1.82 (p, J ¼ 6.4 Hz, 2H), 1.64 (p, J ¼ 6.8 Hz, 2H), 1.57–1.42 solvent was removed under reduced pressure and the residue
(m, 4H) ppm. 13C NMR (125 MHz, CDCl3): d ¼ 162.5, 134.1, was subjected to ash column chromatography (10% EtOAc/
119.4, 115.3, 103.9, 68.3, 51.5, 29.0, 28.9, 26.6, 25.7 ppm. HRMS CH2Cl2) and subsequently crystallized (CH2Cl2/heptane) to
(ESP +ve) calcd for C13H16N4ONa ([M + Na]+): m/z ¼ 267.1217; furnish 4b (141 mg, 72%) as a yellow solid. Rf ¼ 0.66 (5% EtOAc/
1
exp 267.1216.
CH2Cl2). Mp ¼ 54.0–55.7 ꢀC. H NMR (500 MHz, CDCl3): d ¼
4-((8-Azidooctyl)oxy)benzonitrile (14c). Rf ¼ 0.44. Mp ¼ 33.9– 7.92 (d, J ¼ 8.6 Hz, 2H), 7.82 (s, 1H), 7.80 (d, J ¼ 8.6 Hz, 2H), 7.55
36.5 ꢀC. 1H NMR (500 MHz, CDCl3): d ¼ 7.57 (d, J ¼ 8.8 Hz, 2H), (d, J ¼ 8.9 Hz, 2H), 6.94 (s, 1H), 6.91 (d, J ¼ 8.9 Hz, 2H), 6.58 (dd,
6.93 (d, J ¼ 8.8 Hz, 2H), 3.99 (t, J ¼ 6.5 Hz, 2H), 3.26 (t, J ¼ 6.6 Hz, J ¼ 11.2, 6.5 Hz, 1H), 6.48 (dd, J ¼ 11.2, 6.1 Hz, 1H), 6.36 (d, J ¼
2H), 1.80 (p, J ¼ 6.5 Hz, 2H), 1.63–1.56 (m, 2H), 1.53–1.16 (m, 6.5 Hz, 1H), 6.31 (ddd, J ¼ 10.2, 6.1, 2.1 Hz, 1H), 5.83 (dd, J ¼
8H) ppm. 13C NMR (125 MHz, CDCl3): d ¼ 162.5, 134.1, 119.4, 10.2, 3.8 Hz, 1H), 4.44 (t, J ¼ 7.1 Hz, 2H), 3.98 (t, J ¼ 6.3 Hz, 2H),
115.3, 103.8, 68.5, 51.6, 29.3, 29.2, 29.1, 28.9, 26.8, 26.0 ppm. 3.80 (ddd, J ¼ 3.8, 2.1, 2.1 Hz, 1H), 2.01 (p, J ¼ 7.1 Hz, 2H), 1.85–
HRMS (ESP +ve) calcd for C15H20N4ONa ([M + Na]+): m/z ¼ 1.77 (m, 2H), 1.58–1.50 (m, 2H), 1.48–1.40 (m, 2H) ppm. 13C
295.1529; exp 295.1530.
NMR (125 MHz, CDCl3): d ¼ 162.4, 146.9, 139.7, 138.8, 134.1,
4-((9-Azidononyl)oxy)benzonitrile (14d). Rf ¼ 0.49. Mp ¼ 42.5– 132.5, 132.3, 131.1, 131.1, 130.2, 127.8, 126.9, 126.4, 121.3,
43.2 ꢀC. 1H NMR (500 MHz, CDCl3): d ¼ 7.57 (d, J ¼ 8.8 Hz, 2H), 120.1, 119.6, 119.4, 115.3, 112.9, 103.9, 68.1, 51.3, 50.5, 45.3,
6.93 (d, J ¼ 8.8 Hz, 2H), 3.99 (t, J ¼ 6.56 Hz, 2H), 3.26 (t, J ¼ 6.8 30.3, 28.9, 26.3, 25.6 ppm. MS (ESP +ve): m/z ¼ 525 ([M + H]+).
Hz, 2H), 1.79 (t, J ¼ 6.56 Hz, 2H), 1.60 (t, J ¼ 6.8 Hz, 2H), 1.51– Analysis calcd (%) for C33H28N6O (524.63): C 75.55, H 5.38, N
1.25 (m, 10H) ppm. 13C NMR (125 MHz, CDCl3): d ¼ 162.6, 16.02; found: C 75.57, H 5.39, N 16.00.
134.1, 119.5, 115.3, 103.8, 68.5, 51.6, 29.5, 29.3, 29.2, 29.1, 29.0,
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8.9 Hz, 1H), 6.93–6.91 (m, 3H), 6.58 (dd, J ¼ 11.2, 6.4 Hz, 1H), 6.49
(dd, J ¼ 11.2, 6.0 Hz, 1H), 6.36 (d, J ¼ 6.4 Hz, 1H), 6.32 (ddd, J ¼
10.4, 6.1, 1.8 Hz, 1H), 5.83 (dd, J ¼ 10.4, 3.7 Hz, 1H), 4.42 (t, J ¼ 7.0
Hz, 2H), 3.98 (t, J ¼ 6.4 Hz, 2H), 3.81 (ddd, J ¼ 3.7, 1.8, 1.8 Hz, 1H),
1,1-Dicyano-2-(4-(1-(8-(4-cyanophenoxy)octyl)-1H-1,2,3-triazol-
4-yl)phenyl)-1,8a-dihydroazulene (4c). To a degassed solution of
¨
15 (66 mg, 0.235 mmol), 14c (87 mg, 0.318 mmol) and Hunig's
base (10 drops) in toluene (4 mL) was added CuI (7 mg, 0.037
mmol) and the contents stirred for 2 days at rt. The solvent was
removed under reduced pressure and the residue puried by
ash column chromatography (10% EtOAc/CH2Cl2) to furnish
4c (65 mg, 50%) as a yellow solid. Rf ¼ 0.75 (5% EtOAc/CH2Cl2).
Mp ¼ 148.6–152.4 ꢀC. 1H NMR (500 MHz, CDCl3): d ¼ 7.93 (d, J
¼ 8.5 Hz, 2H), 7.81 (s, 1H), 7.79 (d, J ¼ 8.5 Hz, 2H), 7.56 (d, J ¼
8.8 Hz, 2H), 6.93 (s, 1H), 6.91 (d, J ¼ 8.8 Hz, 2H), 6.57 (dd, J ¼
11.3, 6.4 Hz, 1H), 6.48 (dd, J ¼ 11.3, 6.1 Hz, 1H), 6.36 (d, J ¼ 6.4
Hz, 1H), 6.31 (ddd, J ¼ 10.2, 6.1, 2.0 Hz, 1H), 5.83 (dd, J ¼ 10.2,
3.8 Hz, 1H), 4.42 (t, J ¼ 7.1 Hz, 2H), 3.97 (t, J ¼ 6.5 Hz, 2H), 3.80
(ddd, J ¼ 3.8, 2.0, 2.0 Hz, 1H), 2.00–1.96 (m, 2H), 1.81–1.75 (m,
2H), 1.53–1.32 (m, 8H) ppm. 13C NMR (125 MHz, CDCl3): d ¼
162.5, 146.8, 139.7, 138.78, 134.1, 132.5, 132.3, 131.1, 130.1,
127.8, 126.9, 126.4, 121.3, 120.1, 119.6, 119.4, 115.3, 115.3,
112.9, 103.8, 68.4, 51.2, 50.6, 45.2, 30.4, 29.2, 29.0, 29.0, 26.5,
25.9 ppm, 1C masked. HRMS (MALDI +ve) calcd for C35H33N6O
([M + H]+): m/z ¼ 553.2710; exp 553.2716. Analysis calcd (%) for
2.16–1.89 (m, 2H), 1.81–1.75 (m, 2H), 1.49–1.16 (m, 12H) ppm. 13
C
NMR (125 MHz, CDCl3): d ¼ 146.8, 139.8, 138.8, 134.1, 132.5, 132.4,
131.1, 131.1, 130.1, 127.9, 126.9, 126.4, 121.3, 120.1, 119.6, 119.5,
115.3, 115.3, 112.9, 103.8, 68.5, 51.3, 50.7, 45.3, 30.5, 29.5, 29.4,
29.4, 29.1, 29.1, 26.6, 26.1 ppm. HRMS (MALDI +ve) calcd for
C37H36N6O (M+): m/z ¼ 580.2945; exp 580.2951.
1,1-Dicyano-2-(4-octyl-(1H-1,2,3-triazol-4-yl)phenyl)-1,8a-
dihydroazulene (4j). To a degassed solution of 16 (98 mg, 0.350
¨
mmol), octylazide (106 mg, 0.683 mmol) and Hunig's base (10
drops) in toluene (4 mL) was added CuI (11 mg, 0.058 mmol)
and the contents stirred for 2 days at rt. The solvent was
removed under reduced pressure and the residue was subjected
to ash column chromatography (10% EtOAc/CH2Cl2) followed
by crystallization to give pure 4j (147 mg, 97%) as a yellow solid.
1
ꢀ
Rf ¼ 0.84 (5% EtOAc/CH2Cl2). Mp ¼ 126.1–130.6 C. H NMR
(500 MHz, CDCl3): d ¼ 7.94 (d, J ¼ 8.4 Hz, 2H), 7.81 (s, 1H), 7.79
(d, J ¼ 8.4 Hz, 2H), 6.93 (s, 1H), 6.57 (dd, J ¼ 11.2, 6.3 Hz, 1H),
6.48 (dd, J ¼ 11.2, 6.1 Hz, 1H), 6.35 (d, J ¼ 6.3 Hz, 1H), 6.34–6.28
(m, 1H), 5.83 (dd, J ¼ 10.2, 3.6 Hz, 1H), 4.41 (t, J ¼ 7.2 Hz, 2H),
3.80 (ddd, J ¼ 3.7, 1.9, 1.9 Hz, 1H), 1.99–1.91 (m, 2H), 1.97–1.95
(m, 2H), 1.42–1.18 (m, 8H), 0.87 (t, J ¼ 6.8 Hz, 3H) ppm. 13C
NMR (125 MHz, CDCl3): d ¼ 146.6, 139.7, 138.7, 132.3, 130.9,
130.9, 129.9, 127.7, 126.7, 126.3, 121.1, 120.0, 119.5, 115.2,
112.7, 51.1, 50.6, 45.1, 31.7, 30.4, 29.1, 29.0, 26.5, 22.6, 14.1
ppm, 1C masked. HRMS (MALDI +ve) calcd for C28H30N5 ([M +
H]+): m/z ¼ 436.2496; exp 436.2495. Analysis calcd (%) for
C
35H32N6O (552.68): C 76.06, H 5.84, N 15.21; found: C 75.93, H
5.88, N 15.11.
1,1-Dicyano-2-(4-(1-(9-(4-cyanophenoxy)nonyl)-1H-1,2,3-triazol-
4-yl)phenyl)-1,8a-dihydroazulene (4d). To a degassed solution of
¨
15 (49 mg, 0.175 mmol), 14d (49 mg, 0.179 mmol) and Hunig's
base (10 drops) in toluene (4 mL) was added CuI (7 mg, 0.037
mmol) and the contents stirred for 2 days at rt. The solvent was
removed under reduced pressure and the residue was subjected
to ash column chromatography (10% EtOAc/CH2Cl2) followed
by crystallization to give pure 4d (49 mg, 49%) as a yellow solid.
C
28H29N5 (435.58): C 77.21, H 6.71, N 16.08; found: C 77.15, H
1
ꢀ
6.80, N 15.94.
Rf ¼ 0.77 (5% EtOAc/CH2Cl2). Mp ¼ 131.9–148.4 C. H NMR
(500 MHz, CDCl3): d ¼ 7.94 (d, J ¼ 8.4 Hz, 2H), 7.81–7.79 (m,
3H), 7.57 (d, J ¼ 8.77 Hz, 2H), 6.93–6.91 (m, 3H), 6.58 (dd, J ¼
11.3, 6.3 Hz, 1H), 6.49 (dd, J ¼ 11.3, 6.1 Hz, 1H), 6.36 (d, J ¼ 6.3
Hz, 1H), 6.32 (ddd, J ¼ 10.2, 6.1, 2.0 Hz, 1H), 5.83 (dd, J ¼ 10.2,
3.8 Hz, 1H), 4.42 (t, J ¼ 7.1 Hz, 2H), 3.98 (t, J ¼ 6.5 Hz, 2H), 3.81
(ddd, J ¼ 3.8, 2.0, 2.0 Hz, 1H), 1.99–1.96 (m, 2H), 1.78 (p, J ¼ 6.5
Hz, 2H), 1.44–1.41 (m, 2H), 1.37–1.34 (m, 8H) ppm. 13C NMR
(125 MHz, CDCl3): d ¼ 162.4, 146.7, 139.6, 138.7, 134.0, 132.3,
132.2, 131.0, 130.9, 130.0, 127.7, 126.8, 126.3, 121.1, 119.9,
119.5, 119.3, 115.2, 112.7, 103.7, 68.3, 51.1, 50.5, 45.1, 30.3, 29.3,
29.2, 29.0, 28.9, 26.5, 25.9 ppm. HRMS (MALDI +ve) calcd for
2-(2-(Cyclohepta-2,4,6-trien-1-ylidene)-1-(40-(octyloxy)-[1,10-
biphenyl]-4-yl)ethylidene)malononitrile (17). To
a stirred
solution of 3f (418 mg, 0.908 mmol) in CH2Cl2 (50 mL) at rt
under an argon atmosphere, was added AlCl3 (341 mg, 2.56
mmol). Aer continued stirring for approximately 20 min,
TLC analysis indicated the presence of unreacted 3f and
more AlCl3 (183 mg, 1.37 mmol) was added to the vessel and
the reaction allowed to stir a further 20 min. The mixture was
cooled on an ice bath and quenched by addition of ice-water
(100 mL) and the phases separated. The aqueous phase was
extracted with CH2Cl2 (2 ꢂ 50 mL) and the combined organic
phases dried over MgSO4 and ltered. The solution was
diluted with heptane (100 mL) and the CH2Cl2 was removed
C
36H35N6O (M+): m/z ¼ 566.2789; exp 566.2794. Analysis calcd
(%) for C36H34N6O (566.71): C 76.30, H 6.05, N 14.83; found: C
75.92, H 5.70, N 14.71.
ꢀ
by rotary evaporation while being kept at 0 C. The solution
was placed in a freezer resulting in the crystallization of 17,
which was isolated as a dark red solid (368 mg, 88%). This
material was stored in the freezer to prevent ring-closure
back to 3f. Mp ¼ 105–109 ꢀC. 1H NMR (500 MHz, CDCl3):
d ¼ 7.35 (d, J ¼ 8.2 Hz, 2H), 7.35 (d, J ¼ 8.7 Hz, 2H), 7.10 (d, J
¼ 8.2 Hz, 2H), 6.91 (d, J ¼ 8.7 Hz, 2H), 6.12 (s, 1H), 5.80 (dd, J
¼ 11.4, 1.5, 1H), 5.65 (dd, J ¼ 12.2, 2.1 Hz, 1H), 5.59–5.49 (m,
2H), 5.46–5.42 (m, 1H), 5.10 (dd, J ¼ 12.2, 7.8 Hz, 1H), 3.69 (t,
J ¼ 6.5 Hz, 2H), 1.68–1.63 (m, 2H), 1.39–1.34 (m, 2H), 1.33–
1.18 (m, 8H), 0.92 (t, J ¼ 7.0 Hz, 3H) ppm. 13C NMR (125 MHz,
CDCl3): d ¼ 167.8, 160.1, 152.9, 143.7, 142.2, 135.2, 134.7,
1,1-Dicyano-2-(4-(1-(10-(4-cyanophenoxy)deconyl)-1H-1,2,3-triazol-
4-yl)phenyl)-1,8a-dihydroazulene (4e). To a degassed solution of 15
¨
(73 mg, 0.260 mmol), 14e (112 mg, 0.373 mmol) and Hunig's base
(10 drops) in toluene (4 mL) was added CuI (15 mg, 0.079 mmol)
and the contents stirred for 2 days at rt. The solvent was removed
under reduced pressure and the residue was subjected to ash
column chromatography (10% EtOAc/CH2Cl2) followed by crys-
tallization to give pure 4e (73 mg, 48%) as a yellow solid. Rf ¼ 0.80
1
(5% EtOAc/CH2Cl2). Mp ¼ 111.1–115.1 ꢀC. H NMR (500 MHz,
CDCl3): d ¼ 7.94 (d, J ¼ 8.4 Hz, 2H), 7.81–7.79 (m, 3H), 7.56 (d, J ¼
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134.2, 133.3, 133.2, 132.7, 132.1, 129.3, 128.6, 128.4, 127.6,
119.8, 115.3, 78.4, 68.1, 32.2, 29.8, 29.7, 29.7, 26.4, 23.1, 14.4
ppm, 1C masked. HRMS (MALDI +ve) calcd for C32H32N2ONa
[(M + Na)+]: m/z ¼ 483.2407, found m/z ¼ 483.2412. Analysis
calcd (%) for C32H32N2O (496.62): C 83.49, H 7.00, N 6.08;
found: C 83.38, H 7.11, N 6.14.
6 S. Z. Janicki and G. B. Schuster, J. Am. Chem. Soc., 1995, 117,
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7 J. Daub, T. Knochel and A. Mannschreck, Angew. Chem., Int.
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2-(2-(Cyclohepta-2,4,6-trien-1-ylidene)-1-(20,30-diuoro-40-hydroxy-
[1,10-biphenyl]-4-yl)ethylidene)malononitrile (18). To a stirred solu-
tion of 3g (210 mg, 0.423 mmol) in CH2Cl2 (50 mL) at rt, under an
argon atmosphere, was added AlCl3 (1.010 g, 7.58 mmol) and the
mixture was stirred for 20 min. TLC analysis indicated the pres-
T. Vosch, J. Nygard, X. Qiu, W. Hu, Y. Liu, G. C. Solomon,
˚
H. G. Kjaergaard, T. Bjørnholm, M. B. Nielsen,
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ence of unreacted 3g and more AlCl3 (540 mg, 4.05 mmol) was 10 D. Demus, J. Goodby, G. W. Gray, H.-W. Spies and V. Vill,
added, whereby the reaction was allowed to stir a further 20 min.
The mixture was cooled on an ice bath and quenched by addition
Handbook of liquid crystals, Fundamentals, Wiley-VCH, New
York, 1998, ch 6.
of ice-water (100 mL) aer which the phases were separated. The 11 See for example: I. M. Saez and J. W. Goodby, J. Mater. Chem.,
´
aqueous phase was extracted with CH2Cl2 (2 ꢂ 50 mL) and the
combined organic phases was dried with MgSO4 and ltered.
Heptane was added (100 mL), and the solution concentrated under
reduced pressure at 0 ꢀC, whereby the solution was placed at ꢁ18
ꢀC for 16 h, resulting in the crystallization of 18 (85 mg, 52%) as
a dark red solid. This material was stored in the freezer to prevent
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´
ring-closure back to 3g. Mp ¼ 129.7–131.0 (color change to yellow), 12 See for example: H. Sorkin, Mol. Cryst. Liq. Cryst., 1980, 56,
168 (decomposes) ꢀC. 1H NMR (500 MHz, CDCl3): d ¼ 7.61 (d, J ¼
7.9 Hz, 2H), 7.47 (d, J ¼ 7.9 Hz, 2H), 7.13 (td, J ¼ 8.3, 2.2 Hz, 1H),
6.90–6.84 (m, 1H), 6.75–6.69 (m, 1H), 6.45–6.37 (m, 2H), 6.35 (s,
1H), 6.33–6.27 (m, 1H), 5.94 (d, J ¼ 4.6 Hz, 1H), 5.60 (br s, 1H,
279; M. Hara, Y. Iwakabe, K. Tochigi, H. Sasabe,
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NMR (125 MHz, CDCl3): d ¼ 168.4, 154.1, 148.4 (dd, J ¼ 250.4, 11.4
New J. Chem., 2014, 38, 4235.
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18 C. R. Parker, C. G. Tortzen, S. L. Broman, M. Schau-
Acknowledgements
˚
Magnussen, K. Kilsa and M. B. Nielsen, Chem. Commun.,
The Danish Council for Independent Research | Technology
and Production Sciences (#12-126668) and University of
Copenhagen are acknowledged for nancial support. Dr Theis
Brock-Nannestad, University of Copenhagen, is thanked for
helpful discussions.
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21 Z. Puterova, J. Romiszewski, J. Mieczkowski and E. Gorecka,
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89744 | RSC Adv., 2015, 5, 89731–89744
This journal is © The Royal Society of Chemistry 2015