Effect of ring size on photoisomerization properties of stiff stilbene macrocycles

Article abstract of DOI:10.3762/bjoc.15.233

A series of stiff stilbene macrocycles have been studied to investigate the possible impact of the macrocycle ring size on their photodynamic properties. The results show that reducing the ring size counteracts the photoisomerization ability of the macrocycles. However, even the smallest macrocycle studied (stiff stilbene subunits linked by a six carbon chain) showed some degree of isomerization when irradiated. DFT calculations of the energy differences between the E- and Z-isomers show the same trend as the experimental results. Interestingly the DFT study highlights that the energy difference between the E- and Z-isomers of even the largest macrocycle (linked by a twelve carbon chain) is significantly higher than that of the stiff stilbene unit itself. In general, it is indicated that addition of even a flexible chain to the stiff stilbene unit may significantly affect its photochemical properties and increase the photostability of the resulting macrocycle.

Full text of DOI:10.3762/bjoc.15.233

Effect of ring rize on photoisomerization properties
of stiff stilbene macrocycles
Sandra Olsson1, Óscar Benito Pérez2, Magnus Blom1 and Adolf Gogoll*1
Full Research Paper
Open Access
Address:
Department of Chemistry-BMC, Uppsala University, S-751 23
Beilstein J. Org. Chem. 2019, 15, 2408–2418.
doi:10.3762/bjoc.15.233
1
Uppsala, Sweden and 2Faculty of Chemistry, Universitat de
Barcelona, C/ Martí i Franquès 1, 08028 Barcelona, Spain
Received: 27 May 2019
Accepted: 27 September 2019
Published: 11 October 2019
Email:
Adolf Gogoll* - adolf.gogoll@kemi.uu.se
This article is part of the thematic issue "Molecular switches".
Guest Editor: W. Szymanski
*
Corresponding author
Keywords:
DFT; molecular mechanics; photostability; photo-switch; ring-strain;
stiff stilbene
© 2019 Olsson et al.; licensee Beilstein-Institut.
License and terms: see end of document.
Abstract
A series of stiff stilbene macrocycles have been studied to investigate the possible impact of the macrocycle ring size on their
photodynamic properties. The results show that reducing the ring size counteracts the photoisomerization ability of the macro-
cycles. However, even the smallest macrocycle studied (stiff stilbene subunits linked by a six carbon chain) showed some degree of
isomerization when irradiated. DFT calculations of the energy differences between the E- and Z-isomers show the same trend as the
experimental results. Interestingly the DFT study highlights that the energy difference between the E- and Z-isomers of even the
largest macrocycle (linked by a twelve carbon chain) is significantly higher than that of the stiff stilbene unit itself. In general, it is
indicated that addition of even a flexible chain to the stiff stilbene unit may significantly affect its photochemical properties and
increase the photostability of the resulting macrocycle.
Introduction
The stiff stilbene (SS) molecule has drawn a lot of interest due probes [12-18]. While these do incorporate other isomerizable
to its photodynamic properties [1]. Stiff stilbenes typically units in addition to stiff stilbene, we were interested in the
undergo light triggered isomerization from Z to E at 300 nm and effect that the length of an n-alkane chain connecting the two
from E to Z at 360 nm (Scheme 1) [2]. The photochemical halves of stiff stilbene might have. Similar studies, with stil-
mechanism of this reaction is thoroughly described by Quick et bene and pyrene as the modulating units, have recently been
al. [2]. The stiff stilbenes ability to photoisomerize has made it published [19,20]. Our group has reported a SS-based bis-
a useful building block of photodynamic triggers, switches and metalloporphyrin molecular tweezer that binds ditopically to
machines [3-11]. The interplay between the forces involved in guest molecules [21,22]. This kind of complex would behave
the switching action and the pull from groups attached to the like a macrocycle upon photoisomerization, arising the ques-
stiff stilbene has been investigated, e.g., as molecular force tion whether it might be possible to predict such photoisomeriz-
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Beilstein J. Org. Chem. 2019, 15, 2408–2418.
Results and Discussion
Synthesis
ability and to relate it to the length of a ditopically bound guest
molecule connecting the two metalloporphyrin units.
The synthesis of the macrocycles was based on well-estab-
lished reactions (Scheme 2). The indanone is formed by intra-
molecular Friedel–Crafts acylation of 2 under microwave radia-
tion as reported by Oliverio et al. [23]. The second step is the
demethylation of indanone methyl ether 3 by aluminium
trichloride in toluene at reflux [24]. Two indanone units are
then attached to an n-alkanediyl linker using a Williamson ether
synthesis to yield the diethers 6a–d. Finally, the stiff stilbene
unit is formed by an intramolecular McMurry reaction resulting
in 1a–d [25,26]. The Z-isomer is formed in huge excess in these
Scheme 1: The stiff stilbene photoisomerization from Z to E and vice
versa by irradiation at 300 nm and 360 nm, respectively.
To investigate the photoisomerization ability of the stiff stil- reactions and any trace amounts of E-isomer are removed
bene as a macrocycle segment a series of model compounds during purification.
were chosen (Figure 1). To keep the system as simple as
possible the SS was attached to an aliphatic carbon chain via Compared to syntheses of other stiff stilbene macrocycles that
ether groups. Four different lengths of carbon chains were used, typically start from indanone derivatives [15,16], our approach
with distances between the terminal carbons of 6.4 Å (C6), yields the target compounds in fewer steps from a simpler
8
.9 Å (C8), 11.4 Å (C10) and 13.9 Å (C12). The SS-macro- starting material, i.e., 3-(4'-methoxyphenyl)propionic acid
cycles have been studied both experimentally and by computa- (Scheme 2).
tional techniques.
Photoisomerization
Photoisomerizing the (Z)-1a–d to the (E)-1a–d isomers requires
to stretch the linker. The isomerization was achieved by irradia-
tion of a degassed solution of (Z)-1a–d in chloroform or deuter-
ated chloroform using either a 280 or 300 nm filter (Scheme 3).
The conversion was followed by UV–vis or 1H NMR spectros-
copy. Compounds were irradiated until an increase in isomeri-
zation yield could no longer be observed (see Supporting Infor-
mation File 1 for details).
Figure 1: The investigated SS-macrocycles (Z)-1a–d.
Scheme 2: Synthetic route to SS-macrocycles. i. (1) Triflic acid (3 equiv), DCM (dry), Ar atmosphere, MW (110 °C, 1 h), (2) H2O (0 °C). ii. (1) AlCl3
(
(
3 equiv), toluene (dry), Δ 1.5 h, (2) H2O. iii. (1) K2CO3 (4 equiv), TBAB (0.2 equiv), DMF (dry), Ar atmosphere, MW (150 °C, 15 min). iv. (1) TiCl4
3 equiv), Zn powder (6 equiv), THF, Δ, 12 h.
2
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Beilstein J. Org. Chem. 2019, 15, 2408–2418.
The E- and Z-isomers give distinctively separated chemical
shifts for the CH2 protons next to the double bond. This makes
the determination of the Z/E ratio straightforward. The compo-
sition of the photostable mixtures as compared to the noncyclic
reference is presented in Figure 2. As the linker chain gets
shorter the E-isomer becomes less favored. What is particularly
interesting is that even with the longest chain of twelve carbons
a significantly lower amount of E-isomer as compared to the
reference is obtained. Clearly even a loose linking chain has a
considerable effect on the system.
Scheme 3: The photoisomerization of the stiff stilbene macrocycles,
showing the stretching of the linker (grey box).
Computations
To set the results of this photoisomerization into perspective a Relative energies of E- and Z-isomers
noncyclic stiff stilbene was used as a reference (Scheme 4). The The Gibbs free energies of (Z)-1a–d and (E)-1a–d were calcu-
photodynamic properties of this compound have been reported lated at the DFT level using the B3LYP functional with the
previously [27].
6-31G(d,p) basis set and SCRF-SMD solvent model
chloroform) [28-37]. The photoisomerization of stiff stilbenes
(
involves a complex potential energy surface with several
excited species in equilibria, eventually reaching the cis or trans
ground state [2]. Macroscopic parameters such as extinction
coefficients and quantum yields also affect the composition of
the photostationary state. Ground state energies might therefore
not be directly related to the isomerization reaction without in-
vestigation of the exited state potential energy surface. Howev-
er, the difference in Gibbs free energy (ΔG, Figure 3) between
the E- and Z-isomers shows a trend reminiscent of the experi-
mental photoisomerization results (Figure 2), i.e., shorter chain
lengths result in larger ΔG as well as in larger Z:E ratios.
Scheme 4: Noncyclic stiff stilbene diester 7 used as reference in the
photoisomerization study.
Figure 2: The photoisomerization of the SS-macrocycles shows a clear correlation between the Z/E ratio in the photostable mixture and the linker
length. The non-cyclic SS-diester 7 is included as a reference.
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Beilstein J. Org. Chem. 2019, 15, 2408–2418.
Figure 3: Gibbs free energy differences (ΔG) between Z- and E-isomers of 1a–d and of the reference compound 7 calculated using B3LYP. The
results show a pronounced effect of linker length on the energy difference between Z- and E-isomers.
Ring strain
transforming the cyclic diethers into noncyclic diethers (Sup-
The ring strain energies of compounds (Z)-1a–d and porting Information File 1) and the results are visualized in
(
E)-1a–d were calculated for an isodesmic reaction [38] Figure 4.
Figure 4: Ring strain for E and Z-isomers of 1a–d expressed as the Gibbs free energy difference to an acyclic analogue, using an isodesmic reaction
(
Figure S47, Supporting Information File 1).
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For (E)-1a–d the ring strain decreases with increased linker
length. For the less strained (Z)-1a–d the ring strain increases
slightly with increased linker length and for the longer linkers
(
1c,d) the ring strains of the E- and Z-isomers are
similar. The differences in ring strain between the E- and
Z-isomers show an exponential correlation to the linker length
(
Figure 5).
Conformational analysis
To obtain further information regarding the reason for the ob-
served photoisomerization properties of the macrocyclic stiff
stilbene diethers, a conformational analysis was undertaken
(
Figure 6).
According to X-ray crystallography, in compound (E)-7
Scheme 4) the aromatic rings of the two indane units are in the
same plane (dihedral angle 180°), whereas in (Z)-7 this angle is
.1° [21]. In the macrocyclic diethers 1a–d, all Z-isomers have
(
9
a dihedral angle of 12–14°, roughly similar to the one in the
crystal structure of (Z)-7. The deviation of this angle from 0° is
due to steric interaction between two aromatic protons in
position 4 (Figure 9). In the E-isomers, an increasing distortion
of the stiff stilbene segment with decreasing ring size is
indicated by the substantial deviation of the dihedral angle
from 180°. Furthermore, the alkyl chains adopt more similar
conformations in the E-isomers with stretched alkyl chains.
In the Z-isomers, the alkyl chains adopt a larger variety of
conformations. This will add an entropy penalty for the
E-isomers.
Figure 6: Conformer ensembles for the macrocyclic stiff stilbene
diethers 1a–d. Dihedral angles between the two aromatic rings are
given in parentheses.
Figure 5: The differences in ring strain between the E- and Z-isomers show an exponential correlation to the linker length.
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Interatomic distances from NOE buildup rates
Experimental
Interatomic distances, derived from NOE buildup rates, are Starting materials, solvents and reagents were commercially
summarized in Figure 7. Signal overlap prevented an analysis available and used without further purification except dichloro-
accounting for the presence of an ensemble of conformers such methane (DCM), ethyl acetate, pentane, tetrahydrofuran (THF)
as NAMFIS [39,40]. For example, each CH2 signal is gener- and toluene that were distilled before use. N,N-Dimethylform-
ated by four CH2 protons which are chemically equivalent in amide (DMF) was used as supplied (biotech. grade, ≥99.9%).
the averaged chemical structure (≈ the 2D molecular structure) Unless stated differently, all reactions were carried out under
but not in individual conformers. They cannot be distinguished atmospheric pressure and with argon atmosphere.
on the NMR timescale. Therefore, the calculated distances rave,
being averages with contributions from all conformers, are Microwave (MW) heating was carried out in a Biotage+ Initia-
biased for shorter distances, i.e., rave = ⟨1/r6⟩ instead of tor microwave using 10–20 mL Biotech MW vials, applying
rave = 1/⟨r6⟩ [41]. However, they still should allow a compari- MW irradiation at 2.45 GHz, with a power setting up to 40 W
son between the different compounds (Z)-1a–d. Thus, in- and an average pressure of 4–5 bar when DCM was the solvent
creased conformational flexibility is indicated by increasing dis- and 90 W/1 bar when the solvent was DMF. Analytical TLC
tances from (Z)-1a to 1d for methylene protons further along was performed using Merck precoated silica gel 60 F254 plates,
the chain, such as distance 4 and distance 5 (Figure 7). An visualized with UV light and Hannessian's stain (5% ammoni-
exception is the slight decrease of distance 7 when comparing um molybdate, 1% cerium sulfate and 10% sulfuric acid in
(
Z)-1c to (Z)-1d. This might be due to larger mobility of the water). Flash chromatography (CC) was performed over Matrex
alkyl chain.
silica gel (60 Å, 35–70 µm) on a regular column or on a Grace
Reveleris X2 Flash chromatography system.
Conclusion
A series of novel stiff stilbene macrocycles has been synthe- 1H and 13C NMR spectra were recorded on Varian Mercury
sised and used to investigate the effect of the ring size on the Plus (1H at 300.03 MHz), Agilent 400-MR DD2 (1H at
photoisomerization of the stiff stilbene unit. Both experimental 399.98 MHz, 13C at 100.58 MHz), Varian Unity Inova (1H at
photoisomerization and DFT calculations show that the strain of 499.94 MHz) and Bruker Avance Neo (1H at 500.15 MHz, 13C
the linking chain affects the isomerization even for the longest at 125.78 MHz) spectrometers at 25 °C. Chemical shifts (δ) are
chains. As stiff stilbene is gaining popularity as a unit in molec- reported in ppm referenced indirectly to tetramethylsilane via
ular machines and photodynamic systems a clear understanding the residual solvent signal (CDCl3, 1H at 7.26 and 13C at
of the effect of cyclisation on the photoisomerization is of 77.0 ppm). Coupling constants are given in Hz. Signal
general interest.
assignments were derived from 1H-gCOSY [42,43],
Figure 7: Distances derived from NOE buildup experiments. Distances between pairs of protons or groups of protons attached to the indicated
carbons are designated as distance 1 through 8. n.d.: NOE cross peak not detectable. – : distance does not exist.
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Beilstein J. Org. Chem. 2019, 15, 2408–2418.
gTOCSY [44], gHSQC [45], gHMBC [46], and gNOESY [47] Synthesis
spectra. Synthesis of 6-methoxyindan-1-one (3)
Compound 2 (2.523 g, 14.0 mmol) was dissolved in dry DCM
Experimental conditions for NOE buildup experiments: (10 mL) in a flame-dried MW vial and cooled in ice-bath.
gradient enhanced NOESY spectra were obtained for non- TfOH (3.7 mL, 41.9 mmol) was added dropwise. The vial was
degassed solutions (16–46 mM) in CDCl3 at 25 °C, 400 MHz, sealed, the air was replaced by argon gas, and the reaction mix-
mixing times = 0.1, 0.2, 0.3, 0.5, 0.7 s. The distance between ar- ture was heated in the MW to 110 °C, 5 bar, for 1 h. The reac-
omatic ortho protons (H-6 and H-7 in Figure 9) was used as tion mixture was poured on ice. The water phase was extracted
reference distance rref at 2.51 Å. Volume integrals for NOESY three times with DCM (3 × 100 ml). The combined organic
diagonal and cross peaks were measured for mixing times phases were dried over MgSO4 and the solvent was removed by
during the linear NOE buildup phase. For each signal pair A/B rotary evaporation. The crude product was purified by CC
with a NOESY cross peak an average cross peak volume was (pentane/EtOAc 1:0 to 1:4). The solvent was evaporated, giving
calculated from measured volume integrals as:
a light yellow solid, 1.204 g, 53% yield. 1H NMR (CDCl3, 500
MHz) δ 7.37 (m, 1H, Ar-H), 7.20 (m, 1H, Ar-H), 7.18 (m, 1H,
Ar-H), 3.84 (s, 3H, OCH3), 3.07 (m, 2H, CH2CH2CO), 2.72 (m,
2
1
1
2
H, CH2CO); 13C NMR (CDCl3, 100.6 MHz) δ 207.0 (CO),
59.4 (C-OCH3), 148.0 (C, Ar), 138.2 (C, Ar), 127.3 (CH, Ar),
24.0 (CH, Ar), 104.9 (CH, Ar), 55.6 (OCH3), 37.0 (CH2CO),
5.1 (CH2CH2CO); APCI–MS m/z: [M + H]+ calcd for
(
1)
The slope σ from the plot of average volume vs mixing time C10H10O2, 163; found, 163. Data in agreement with the litera-
was determined and from it the distance rAB calculated ture [51].
assuming rAB = rref(σref/σAB)1/6.
Synthesis of 6-hydroxyindan-1-one (4)
Mass spectra were obtained on an Advion Expression-L CMS Compound 3 (1.367 g, 8.4 mmol) and AlCl3 (3.483 g,
with APCI+ interface. High-resolution mass spectra were ob- 26.1 mmol) were dissolved in dry toluene (50 mL) and re-
tained on a Thermo Scientific Q-Exactive instrument in APCI fluxed for 1.5 h. The reaction mixture was cooled to rt. H2O
positive mode. UV–vis spectra were recorded on a Shimadzu (70 mL) was added and the organic phase collected. The water
UV-1650PC spectrophotometer using 10 mm quartz cuvettes. phase was extracted three times with EtOAc (3 × 50 mL). The
Photoisomerizations were performed using an Oriel 1000 W Xe combined organic phases were washed with brine two times
ARC light source equipped with a band pass filter 10BPF10- (2 × 75 mL) and dried over MgSO4. The solvent was removed
3
00 or 10BPF10-280 (Newport).
by rotary evaporation. The orange crude product was purified
by CC (pentane/EtOAc 1:0 to 1:4). The solvent was evaporated,
giving a light orange solid, 1.103 g, 81% yield. 1H NMR
Computational details
The DFT calculations on the stiff stilbene macrocycles were (CDCl3, 500 MHz) δ 7.36 (d, J = 8.3 Hz, 1H, Ar-H), 7.22 (d,
performed with the B3LYP functional as implemented in the J = 2.4 Hz, 1H, Ar-H), 7.16 (dd, J = 2.4, 8.3 Hz, 1H, Ar-H),
Gaussian 16 program package [28-32]. The SCRF solvent 5.67 (s, 1H, OH), 3.08 (m, 2H, CH2CH2CO), 2.73 (m, 2H,
model with the SMD variation was used with chloroform CH2CO); 13C NMR (CDCl3, 100.6 MHz) δ 207.4 (CO), 155.4
as solvent [33-36]. Geometries were optimized using the (C-OH), 147.8 (C, Ar), 138.3 (C, Ar), 127.6 (CH, Ar), 123.4
6
-31G(d,p) basis set [37]. Frequency calculations were (CH, Ar), 108.7 (CH, Ar), 37.0 (CH2CO), 25.1 (CH2CH2CO);
performed at the same level to confirm that a minimum APCI–MS m/z: [M + H]+ calcd for C9H8O2, 149; found, 149.
had been reached and to extract free energy corrections, which Data in agreement with the literature [52].
were evaluated at 298.15 K. A stability analysis was performed
to ensure that a stable wave-function was attained for all General procedure A: Williamson ether
species.
synthesis (assisted by MW)
Compound 4 (2 equiv), dibromoalkane 5 (1 equiv), TBAB
Conformational analyses of the stiff stilbene macrocycles (0.2 equiv) and K2CO3 (4 equiv) were dissolved in dry DMF
were calculated in MacroModel 9.9 with the OPLS3e force (15 mL) in a flame-dried MW vial. The vial was sealed, put
field, CHCl3 as solvent and dielectric constant 9.1 [48,49]. under argon and heated in the MW to 150 °C for 15 min (the
Redundant conformer elimination in MacroModel was reaction was followed by NMR). The reaction mixture was
used to reduce the number of conformations to 10–20 struc- cooled to rt and poured on DCM (40 mL), filtered and washed
tures [50].
with water four times (4 × 50 mL) and brine three times
2
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Beilstein J. Org. Chem. 2019, 15, 2408–2418.
(
3 × 50 mL). The organic phase was dried over MgSO4 and the 1.3 mmol) as starting materials, giving a light brown solid
solvent removed by rotary evaporation. The product was dried which was sufficiently pure for subsequent steps, 0.471 g,
under high vacuum overnight.
80% yield. 1H NMR (CDCl3, 500 MHz) δ 7.34 (m, 2H, H-7),
7
3
1
.20–7.16 (m, 4H, H-4 H-6), 3.98 (t, J = 6.8 Hz, 4H, CH2-1’),
.07 (m, 4H, CH2-1), 2.71 (m, 4H, CH2-2), 1.79 (dt, J = 6.8,
5.0 Hz, 4H, CH2-2’), 1.46 (m, 4H, CH2-3’), 1.40–1.30 (m, 8H,
CH2-4’ CH2-5’); 13C NMR (CDCl3, 100.6 MHz) δ 207.1 (C,
C-3), 158.9 (C, C-5), 147.8 (C, C-3a), 138.2 (C, C-7a), 127.3
(
3
(
[
CH, C-7), 124.4 (CH, C-6), 105.6 (CH, C-4), 68.4 (CH2, C-1’),
7.0 (CH2, C-2), 29.4 (CH2, C-5’), 29.2 (CH2, C-4’), 29.1
CH2, C-2’), 26.0 (CH2, C-3’), 25.1 (CH2, C-1); APCI–MS m/z:
Figure 8: Numbering of carbons in compounds 6a–d, showing 6d as
an example.
M + H]+ calcd for C28H34O4, 435; found, 435. HRMS (CI)
Synthesis of 6-[2-(3-oxoindan-5-
yl)oxyhexyloxy]indan-1-one (6a)
The synthesis followed general procedure A with compound 4
m/z: [M + H]+ calcd for C28H34O4, 435.2530; found: 435.2527;
UV–vis (CH2Cl2) λmax: 320, 248 nm.
(
0
0.201 g, 1.4 mmol) and 1,6-dibromohexane (5a, 0.11 mL, Synthesis of 6-[2-(3-oxoindan-5-yl)oxydo-
.7 mmol) as starting materials, giving a brown solid which was decyloxy]indan-1-one (6d)
sufficiently pure for subsequent steps, 0.176 g, 69% yield. The synthesis followed General procedure A with compound 4
H NMR (CDCl3, 500 MHz) δ 7.36 (m, 2H, H-7), 7.20–7.16 (0.102 g, 0.7 mmol) and 1,12-dibromododecane 5d (0.112 g,
m, 4H, H-4 H-6), 4.00 (t, J = 6.6 Hz, 4H, CH2-1’), 3.07 (m, 3.5 × 10−2 mmol) as starting materials, giving a light brown
H, CH2-1), 2.72 (m, 4H, CH2-2), 1.84 (m, 4H, CH2-2’), 1.54 solid which was sufficiently pure for subsequent steps, 0.112 g,
m, 4H, CH2-3’); 13C NMR (CDCl3, 100.6 MHz) δ 207.1 (C, 71% yield. 1H NMR (CDCl3, 500 MHz) δ 7.36 (m, 2H, H-7),
C-3), 158.8 (C, C-5), 147.8 (C, C-3a), 138.2 (C, C-7a), 127.3 7.20–7.17 (m, 4H, H-4 H-6), 3.98 (t, J = 6.8 Hz, 4H, CH2-1’),
CH, C-7), 124.4 (CH, C-6), 105.6 (CH, C-4), 68.2 (CH2, C-1’), 3.07 (m, 4H, CH2-1), 2.71 (m, 4H, CH2-2), 1.79 (dt, J = 6.8,
7.0 (CH2, C-2), 29.0 (CH2, C-2’), 25.8 (CH2, C-3’), 25.1 14.8 Hz, 4H, CH2-2’), 1.45 (m, 4H, CH2-3’), 1.39–1.27 (m,
CH2, C-1); APCI–MS m/z: [M + H]+ calcd for C24H26O4, 379; 12H, CH2-4’ CH2-5’ CH2-6’); 13C NMR (CDCl3, 100.6 MHz)
1
(
4
(
(
3
(
found, 379; UV–vis (CH2Cl2) λmax: 320, 249 nm.
δ 207.1 (C, C-3), 158.9 (C, C-5), 147.7 (C, C-3a), 138.2 (C,
C-7a), 127.3 (CH, C-7), 124.4 (CH, C-6), 105.6 (CH, C-4), 68.4
(CH2, C-1’), 37.0 (CH2, C-2), 29.5 (CH2, 4C, C-5’ C-6’), 29.3
(CH2, C-4’), 29.1 (CH2, C-2’), 26.0 (CH2, C-3’), 25.1 (CH2,
Synthesis of 6-[2-(3-oxoindan-5-
yl)oxyoctyloxy]indan-1-one (6b)
The synthesis followed general procedure A with compound 4 C-1); APCI–MS: m/z: [M + H]+ calcd for C30H38O4, 463;
(
0
0.115 g, 0.8 mmol) and 1,8-dibromooctane (5b, 0.07 mL, found, 463; HRMS (CI) m/z: [M + H]+ calcd for C30H38O4,
.4 mmol) as starting materials, giving an orange solid which 463.2843; found, 463.2836; UV–vis (CH2Cl2) λmax: 320,
was sufficiently pure for subsequent steps, 0.121 g, 78% yield. 248 nm.
H NMR (CDCl3, 500 MHz) δ 7.36 (m, 2H, H-7), 7.20–7.16
m, 4H, H-4 H-6), 3.98 (t, J = 6.6 Hz, 4H, CH2-1’), 3.06 (m, General procedure B: McMurry coupling
1
(
4
4
H, CH2-1), 2.71 (m, 4H, CH2-2), 1.80 (dt, J = 6.6, 14.8 Hz, Zinc powder previously grinded (12 equiv) was suspended in
H, CH2-2’), 1.47 (m, 4H, CH2-3’), 1.40 (m, 4H, CH2-4’); dry THF (30 mL). The suspension was cooled to 0 °C in an ice
1
3C NMR (CDCl3, 100.6 MHz) δ 207.1 (C, C-3), 158.8 (C, bath and TiCl4 (6 equiv) added over 10 minutes. The resulting
C-5), 147.8 (C, C-3a), 138.2 (C, C-7a), 127.3 (CH, C-7), 124.4 slurry was refluxed for 1.5 h. A solution of compound 6 in dry
CH, C-6), 105.6 (CH, C-4), 68.3 (CH2, C-1’), 37.0 (CH2, C-2), THF (50–100 mL) was added over a 5–7 h period to the
9.2 (CH2, C-4’), 29.1 (CH2, C-2’), 25.9 (CH2, C-3’), 25.1 refluxing reaction mixture by syringe pump. The refluxing was
CH2, C-1); APCI–MS m/z: [M + H]+ calcd for C26H30O4, 407; continued for 40 min after the addition was complete. The reac-
found, 407; HRMS (CI) m/z: [M + H]+ calcd for C26H30O4, tion mixture was cooled to rt and poured on a saturated aqueous
(
2
(
4
2
07.2217; found, 407.2217; UV–vis (CH2Cl2) λmax: 320, solution of NH4Cl. The water phase was extracted three times
49 nm.
with DCM (3 × 100 mL). The combined organic phases were
washed two times with brine (2 × 100 mL) then dried over
MgSO4 and the solvent was removed by rotary evaporation.
Unless stated differently, the obtained yellow oil was purified
Synthesis of 6-[2-(3-oxoindan-5-
yl)oxydecyloxy]indan-1-one (6c)
The synthesis followed general procedure A with compound 4 by CC (pentane/DCM 1:0 to 1:1). The obtained product was
(
0.397 g, 2.7 mmol) and 1,10-dibromodecane 5c (0.405 g, dried under high vacuum overnight.
2
415

Beilstein J. Org. Chem. 2019, 15, 2408–2418.
J = 5.9, 12.6 Hz, 4H, CH2-3’), 1.45–1.37 (m, 8H, CH2-4’ CH2-
5
’); 13C NMR (CDCl3, 100.6 MHz) δ 157.7 (C, C-5), 141.7 (C,
C-7a), 140.4 (C, C-3a), 135.5 (C, C-3), 125.4 (CH, C-7), 113.6
CH, C-6), 109.5 (CH, C-4), 67.1 (CH2, C-1’), 35.6 (CH2, C-2),
9.8 (CH2, C-1), 28.4 (CH2, C-2’), 26.9 (CH2, C-4’), 26.4
CH2, C-5’), 24.8 (CH2, C-3’); APCI–MS m/z: [M + H]+ calcd
(
2
(
for C28H34O2, 403; found, 403; HRMS (CI) m/z: [M + H]+
calcd for C28H34O2, 403.2632; found: 403.2624; UV–vis
Figure 9: Numbering of carbons in compounds (Z)-1a–d, showing
Z)-1d as an example.
(
(
CH2Cl2) λmax: 361, 349, 301, 252 nm.
Synthesis of macrocyclic stiff stilbene diether (Z)-1a
Synthesis of macrocyclic stiff stilbene diether (Z)-1d
The synthesis followed general procedure B with compound 6a The synthesis followed general procedure B with compound 6d
0.279 g, 0.7 mmol) as starting material and gave the pure prod- (0.312 g, 0.7 mmol) as starting material and gave the pure prod-
uct as a light yellow solid, 0.093 g, 37% yield. 1H NMR uct as a light yellow solid, 0.152 g, 52% yield. 1H NMR
CDCl3, 500 MHz) δ 7.75 (d, J = 2.3 Hz, 2H, H-4), 7.19 (d, (CDCl3, 500 MHz) δ 7.64 (d, J = 2.4 Hz, 2H, H-4), 7.19 (d,
J = 8.0 Hz, 2H, H-7), 6.80 (dd, J = 2.3, 8.0 Hz, 2H, H-6), 4.07 J = 8.3 Hz, 2H, H-7), 6.76 (dd, J = 2.4, 8.3 Hz, 2H, H-6), 3.91
t, J = 6.5 Hz, 4H, CH2-1’), 2.94 (m, 4H, CH2-1), 2.82 (m, 4H, (t, J = 6.3 Hz, 4H, CH2-1’), 2.93 (m, 4H, CH2-1), 2.82 (m, 4H,
CH2-2), 1.80 (m, 4H, CH2-2’), 1.59 (m, 4H, CH2-3’); 13C NMR CH2-2), 1.76 (dt, J = 6.3, 15.0 Hz, 4H, CH2-2’), 1.49 (m, 4H,
(
(
(
(
(
CDCl3, 100.6 MHz) δ 157.6 (C, C-5), 141.6 (C, C-7a), 141.1 CH2-3’), 1.44–1.26 (m, 12H, CH2-4’ CH2-5’ CH2-6’);
C, C-3a), 135.2 (C, C-3), 125.5 (CH, C-7), 116.2 (CH, C-6), 13C NMR (CDCl3, 100.6 MHz) δ 157.8 (C, C-5), 141.6 (C,
1
11.9 (CH, C-4), 69.7 (CH2, C-1’), 35.0 (CH2, C-2), 30.0 (CH2, C-7a), 140.5 (C, C-3a), 135.4 (C, C-3), 125.4 (CH, C-7), 114.1
C-1), 28.8 (CH2, C-2’), 24.4 (CH2, C-3’); APCI–MS m/z: (CH, C-6), 109.3 (CH, C-4), 68.4 (CH2, C-1’), 35.5 (CH2, C-2),
M + H]+ calcd for C24H26O2, 347; found, 347; HRMS (CI) 29.8 (CH2, C-1), 29.6 (CH2, C-2’), 27.4 (CH2, C-4’), 27.1
m/z: [M + H]+ calcd for C24H26O2, 347.2006; found, 347.1996; (CH2, C-5’), 26.2 (CH2, C-6’), 25.1 (CH2, C-3’); APCI–MS
[
UV–vis (CH2Cl2) λmax: 350, 298, 253 nm.
m/z: [M + H]+ calcd for C30H38O2, 431; found, 431;
HRMS (CI) m/z: [M + H]+ calcd for C30H38O2, 431.2945;
found, 431.2928; UV–vis (CH2Cl2) λmax: 359, 349, 298,
Synthesis of macrocyclic stiff stilbene diether (Z)-1b
The synthesis followed general procedure B with compound 6b 252 nm.
(
0.105 g, 0.3 mmol) as starting material and gave the pure prod-
uct as a light yellow solid, 0.038 g, 39% yield. 1H NMR Photoisomerizations (followed by NMR
CDCl3, 500 MHz) δ 7.69 (d, J = 2.5 Hz, 2H, H-4), 7.18 (d, spectroscopy)
J = 8.2 Hz, 2H, H-7), 6.74 (dd, J = 2.5, 8.2 Hz, 2H, H-6), 3.97 CDCl3 solutions of products (Z)-1d and stiff stilbene were irra-
t, J = 6.1 Hz, 4H, CH2-1’), 2.93 (m, 4H, CH2-1), 2.82 (m, 4H, diated after degassing by argon bubbling for 15 min. As reac-
(
(
CH2-2), 1.82 (dt, J = 6.1, 12.8 Hz, 4H, CH2-2’), 1.56 (m, 4H, tion vessels, 5 mm NMR tubes, type 5Hp, 178 mm were used.
CH2-3’), 1.45 (m, 4H, CH2-4’); 13C NMR (CDCl3, 100.6 MHz) The course of isomerization was assessed by 1H NMR spectros-
δ 157.6 (C, C-5), 141.6 (C, C-7a), 140.5 (C, C-3a), 135.4 (C, copy.
C-3), 125.4 (CH, C-7), 113.9 (CH, C-6), 110.0 (CH, C-4), 68.1
(
CH2, C-1’), 35.4 (CH2, C-2), 29.8 (CH2, C-1), 28.1 (CH2, Photoisomerizations (followed by UV–vis
C-2’), 27.6 (CH2, C-4’), 25.3 (CH2, C-3’); APCI–MS m/z: spectroscopy)
M + H]+ calcd for C26H30O2, 375; found, 375; HRMS (CI) CHCl3 solutions of products (Z)-1d and stiff stilbene were irra-
m/z: [M + H]+ calcd for C26H30O2, 375.2319; found, 375.2311; diated after degassing by argon bubbling for 15 min. As reac-
[
UV–vis (CH2Cl2) λmax: 361, 349, 300, 253 nm.
tion vessels, 10 mm quartz UV–vis cuvettes were used. The
course of isomerization was assessed by UV–vis spectroscopy.
Synthesis of macrocyclic stiff stilbene diether (Z)-1c
The synthesis followed general procedure B with compound 6c
Supporting Information
(
0.350 g, 0.8 mmol) as starting material and gave the pure prod-
uct as a light yellow solid, 0.171g, 53% yield. 1H NMR
CDCl3, 500 MHz) δ 7.66 (d, J = 2.4 Hz, 2H, H-4), 7.19 (d,
J = 8.3 Hz, 2H, H-7), 6.75 (dd, J = 2.4, 8.3 Hz, 2H, H-6), 3.92
t, J = 5.9 Hz, 4H, CH2-1’), 2.93 (m, 4H, CH2-1), 2.82 (m, 4H,
CH2-2), 1.79 (dt, J = 5.9, 12.6 Hz, 4H, CH2-2’), 1.55 (dt,
Supporting Information File 1
Experimental and theoretical data.
(
[
https://www.beilstein-journals.org/bjoc/content/
(
supplementary/1860-5397-15-233-S1.pdf]
2
416

Beilstein J. Org. Chem. 2019, 15, 2408–2418.
1
1
3.Yang, Q.-Z.; Huang, Z.; Kucharski, T. J.; Khvostichenko, D.; Chen, J.;
Boulatov, R. Nat. Nanotechnol. 2009, 4, 302–306.
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Acknowledgements
This study made use of the NMR Uppsala infrastructure, which
is funded by the Department of Chemistry - BMC and the
Disciplinary Domain of Medicine and Pharmacy. Financial
support by the Swedish Research Council (grant nr. 621-2012-
3
379) and by the Carl Tryggers Foundation (CTS 16:156) is
15.Kucharski, T. J.; Huang, Z.; Yang, Q.-Z.; Tian, Y.; Rubin, N. C.;
Concepcion, C. D.; Boulatov, R. Angew. Chem., Int. Ed. 2009, 48,
gratefully acknowledged. The computations were performed on
resources provided by the Swedish National Infrastructure for
Computing (SNIC) at National Supercomputer Centre (NSC),
Linköping University. We are indebted to Dr. Lisa Haigh,
Imperial College London, Department of Chemistry, Mass
spectrometry service, for the HRMS analyses.
7
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