Starazo triple switches - synthesis of unsymmetrical 1,3,5-tris(arylazo)benzenes

Article abstract of DOI:10.3762/bjoc.16.4

Multistate switches allow to drastically increase the information storage capacity and complexity of smart materials. In this context, unsymmetrical 1,3,5-tris(arylazo)benzenes - 'starazos' - which merge three photoswitches on one benzene ring, were succe

Full text of DOI:10.3762/bjoc.16.4

Starazo triple switches – synthesis of unsymmetrical
1,3,5-tris(arylazo)benzenes
Andreas H. Heindl1,2 and Hermann A. Wegner*1,2
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2020, 16, 22–31.
1Institute of Organic Chemistry, Justus Liebig University,
Heinrich-Buff-Ring 17, 35392 Giessen, Germany and 2Center for
Material Research (LaMa), Justus Liebig University,
Heinrich-Buff-Ring 16, 35392 Giessen, Germany
doi:10.3762/bjoc.16.4
Received: 11 November 2019
Accepted: 09 December 2019
Published: 03 January 2020
Email:
Hermann A. Wegner* -
Associate Editor: P. J. Skabara
hermann.a.wegner@org.chemie.uni-giessen.de
© 2020 Heindl and Wegner; licensee Beilstein-Institut.
License and terms: see end of document.
* Corresponding author
Keywords:
multistate photoswitches; synthesis; tris(arylazo)benzene
Abstract
Multistate switches allow to drastically increase the information storage capacity and complexity of smart materials. In this context,
unsymmetrical 1,3,5-tris(arylazo)benzenes – ‘starazos’ – which merge three photoswitches on one benzene ring, were successfully
prepared. Two different synthetic strategies, one based on Baeyer–Mills reactions and the other based on Pd-catalyzed coupling
reactions of arylhydrazides and aryl halides, followed by oxidation, were investigated. The Pd-catalyzed route efficiently led to the
target compounds, unsymmetrical tris(arylazo)benzenes. These triple switches were preliminarily characterized in terms of their
isomerization behavior using UV–vis and 1H NMR spectroscopy. The efficient synthesis of this new class of unsymmetrical
tris(arylazo)benzenes opened new avenues to novel multistate switching materials.
Introduction
The reversible photochemically induced structural change of prolongs the thermal stability up to years [4], while electron-do-
azobenzenes (ABs) opens various ways towards systems manip- nating groups attached to the different phenyl rings decrease the
ulations on the molecular level [1,2]. Upon irradiation with UV thermal half-lives below the time scale of seconds. Even subtle
light (ca. 350 nm), the thermodynamically more stable (E)-AB interactions, such as London dispersion in alkyl-substituted
isomerizes to the higher-energy Z-isomer [3]. The isomeriza- ABs, can have a significant influence on their isomerization
tion can be reversed either by irradiation with visible light (ca. properties [3,4]. Also, the incorporation of AB units into cyclic
450 nm) or thermally, upon heating. The thermal back-isomeri- [5] or macrocyclic structures can control the switching,
zation rate can be controlled by various factors: Functional depending, i.a., on symmetry and ring strain [6-9]. By combin-
group substitutions on the phenyl rings determine the thermal ing these approaches, half-lives can be tuned from milliseconds
half-lives of (Z)-ABs [1]. For example, o-fluoro substitution to years.
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Beilstein J. Org. Chem. 2020, 16, 22–31.
The incorporation of multiple AB units into one molecule tris(arylazo)benzenes 3 was developed. With an efficient
allows to access multiple states upon isomerization, which preparative access, this highly interesting class of multistate
dramatically increases the potential for information storage photoswitches would be accessible for detailed spectroscopic
using this photoswitch. Ideally, one molecule can be treated investigations, leading to fundamental insights applicable to the
with multiple different inputs, leading to defined, detectable design of intelligent photoresponsive materials.
outputs. An example of such compounds are 1,3,5-
tris(arylazo)benzenes – ‘starazos’ – introduced by Cho and Results and Discussion
co-workers in 2004 (Figure 1) [10]. Despite their successful Initially, two different synthetic strategies were evaluated for
synthesis, using Pd-catalyzed coupling reactions of aryl halides the preparation of tris(arylazo)benzenes 3. The first one relied
and arylhydrazides [11] followed by Cu(I)-mediated oxidation, on the consecutive condensation of anilines with nitroso com-
the photochemical properties of such compounds have not been pounds, Baeyer–Mills reactions [13]. With a suitable protecting
studied yet. Going one step further, this type of compounds group strategy, the selective construction of the individual AB
could be substituted in an unsymmetrical way with different azo branches should be achievable (Scheme 1). Starting from 3,5-
units, which allowed individual switching using light of differ- disubstituted nitrosobenzene E, consecutive Bayer–Mills and
ent wavelengths [12]. These compounds were then investigated deprotection reactions would lead to the target compound 3 in
theoretically by Dreuw and co-workers, who suggested five steps. Furthermore, by using nitrosoarene E, the selective
tris(arylazo)benzene 2 (Figure 1) to feature spectrally separated installment of the amine groups, e.g., via acetamide- and nitro
absorption bands for each AB branch. The authors could show group-carrying intermediates, could be achieved [14-16]. Such
that the excited states of the AB branches in tris(arylazo)- a strategy had already been used successfully in previous syn-
benzenes were electronically decoupled, despite the spatial theses of o-, p-, and m-bis(arylazo)benzenes in our laboratory
overlap. Hence, only four phenyl rings were sufficient for the [14]. However, multiple protection/deprotection steps lowered
construction of three individually photoisomerizable azo units. the atom economy and increased the step count of this strategy.
Motivated by the promising theoretical results by Dreuw and The second approach towards tris(arylazo)benzenes 3 relied on
co-workers [12], an efficient synthetic strategy for asymmetric Pd-catalyzed coupling reactions and Cu(I) oxidation, as
Figure 1: 1,3,5-Tris(arylazo)benzenes as individually switchable multistate photoswitches: previous [11,12] and present work.
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Beilstein J. Org. Chem. 2020, 16, 22–31.
Scheme 1: Synthetic strategy towards 1,3,5-tris(arylazo)benzenes 3 based on consecutive Baeyer–Mills reactions.
presented by Cho and co-workers (Scheme 2) [10]. This route in the first coupling reaction, which would lead to lower yields
offers the advantage that the preparation of a wide variety of of the desired monocoupled intermediates.
N-(tert-butoxycarbonyl)phenylhydrazides has already been re-
ported [17-19]. Additionally, starting from easily accessible As target compounds, tris(arylazo)benzenes (Figure 1) with an
3,5-dibromoazobenzenes H, only two consecutive coupling electron-neutral, electron-donating, and electron-poor (3a), or
reactions, followed by oxidation, would be required to obtain with two different electron-donating (3b) azobenzene frag-
the target starazo 3. However, selectivity might be problematic ments were envisioned to test both synthetic strategies. First,
Scheme 2: Preparation of tris(arylazo)benzenes 3 by Pd-catalyzed cross-coupling reactions of N-Boc-arylhydrazides and bromo-substituted ABs, fol-
lowed by oxidation.
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Beilstein J. Org. Chem. 2020, 16, 22–31.
the Bayer–Mills route was followed. The azobenzene building using sodium hydrosulfide did not yield the desired (E)-N-(3-
block 8, with an unsubstituted phenyl ring and two orthogonal amino-5-(phenyldiazenyl)phenyl)acetamide (9). Alternative
nitrogen substituents in the 3- and 5-position (Scheme 3), was reduction attempts, such as using Pd/C-catalyzed reduction by
prepared. The synthesis commenced with the acetylation of 3,5- H2 in different solvents, SnCl2, or iron under acidic conditions
dinitroaniline (4) in 95% yield, followed by the selective reduc- were not successful either. In all cases, the reactions produced
tion of one nitro group using an aqueous ammonium sulfide complicated mixtures, and the target compound could neither be
solution to furnish aniline 6 in 65% yield [20]. After oxidation identified nor isolated. At this stage, the second strategy via
of 6 to its nitroso analogue 7 [21], a Baeyer–Mills reaction with Pd-catalyzed coupling reaction was assayed [10,11].
aniline yielded the targeted azobenzene building block 8 in 87%
yield (i.e., 53% yield over four steps).
In order to investigate the applicability of the Pd-catalyzed
route to C2-symmetric compounds, 1,3-bis(4-methoxyphenyl-
After the successful synthesis of (E)-N-(3-nitro-5-(phenyl- azo)-5-phenylazobenzene (14) was targeted. First, via coupling
diazenyl)phenyl)acetamide (8), the reduction of the nitro group of 3,5-dibromoazobenzene (11) [22,23] using 2.2 equiv of
was attempted. However, the literature-known procedure of 4-methoxyphenyl-N-Boc-hydrazide (12, Scheme 4). The reac-
Scheme 3: Synthesis of azobenzene building block 8.
Scheme 4: Synthesis of 1,3-bis(4-methoxyphenylazo)-5-phenylazobenzene (14).
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Beilstein J. Org. Chem. 2020, 16, 22–31.
tion yielded the intermediate 13 in 58% yield, using slightly found that the second coupling, leading to the bis(arylhy-
modified conditions compared to the literature protocol [10]. drazide) products 17c/17d, showed higher reaction rates
The CuI-mediated oxidation of the bis(arylhydrazide) 13 (Scheme 6). For the reaction of 15 with (4-methoxyphenyl)-N-
afforded the desired tris(arylazo)benzene 14 in only 19% yield, Boc-hydrazide, 21% of the starting material 15 were recovered,
which was significantly lower compared to the literature-known indicating 79% conversion.
data for symmetric tris(arylazo)benzenes 1.
Nevertheless, both AB 15 as well as the arylhydrazides could be
After this preliminary test, the synthesis of unsymmetrical prepared on a multigram scale, which allowed to access the
tris(arylazo)benzenes 3a/3b was attempted (Scheme 5). In order desired monocoupling products 16a/16b on a scale of several
to install the first, electron-rich 2,4,6-trimethoxyazobenzene hundred milligrams. Their 1H NMR spectra indicated the pres-
fragment, 3,5-dibromoaniline (10) was diazotized and treated ence of mixtures of several isomers, not only E- and Z-configu-
with 1,3,5-trimethoxybenzene to afford (E)-1-(3,5-dibro- ration of the AB, but also different configurations of the Boc
mophenyl)-2-(2,4,6-trimethoxyphenyl)diazene (15) in high groups. However, the coupling products could be unequivo-
yield. Unfortunately, the following monocoupling step using cally identified by high-resolution mass spectrometry. Next,
(4-cyanophenyl)- or (4-methoxyphenyl)arylhydrazides turned 16a/16b were coupled with N-Boc-N-phenylhydrazine to afford
out to be rather ineffective. The desired monocoupling prod- the corresponding tris(arylazo)benzene precursors 17a in 23%
ucts 16a/16b could only be isolated in ca. 10% yield. It was and 17b in 52% yield, respectively (Scheme 5). Again, like for
Scheme 5: Synthesis of unsymmetrical tris(arylazo)benzenes 3a/3b using Pd-catalyzed coupling reactions and CuI-mediated oxidation as key steps.
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Beilstein J. Org. Chem. 2020, 16, 22–31.
Scheme 6: Coupling reactions of 15 with the corresponding arylhydrazides to access monocoupled (16a/16b) and biscoupled compounds (17c/17d)
as major products.
the first coupling reaction, it was not possible to isolate the extent, while for starazo 3b, the expected switching behavior
products as uniform isomers using chromatographic methods. was more pronounced. Furthermore, the irradiation time for
Hence, the tris(arylazo)benzene precursors 17a/17b were used reaching the photostationary state (PSS) of 3a was significantly
without further purification.
longer compared to 3b or other AB derivatives. Afterwards, the
solutions were irradiated with light of 448 nm to photochemi-
Initially, a coupling reaction of N-Boc-N-phenylhydrazine with cally induce Z-to-E isomerization. In both cases, spectra of
AB 15 was attempted. However, with this inversed reaction se- PSSs with slightly higher E/Z ratio could be reached (Figure 2b
quence, inseparable mixtures of the desired coupling product and Figure 2c). This is consistent with the fact that the
and the AB starting material 15 were obtained. Hence, cou- tris(arylazo)benzenes 3a/3b were isolated as mixtures of the all-
pling of the electron-poor and electron-rich arylhydrazides was E-isomers including small amounts of other photoisomers after
performed first to allow the isolation of 16a/16b by chromato- the synthesis. Furthermore, the all-E states could be reached
graphic methods.
after only 20 and 7 s of irradiation, respectively, which was sig-
nificantly faster than the E→Z photoisomerization. All in all,
Finally, the target tris(arylazo)benzenes 3a/3b were obtained by the irradiation experiments revealed that the methoxy-substi-
oxidation of the precursors 17a/17b using CuI under basic tuted derivative 3b shows reversible photoisomerization, while
conditions in DMF at elevated temperature (Scheme 5). For the cyano-substituted tris(arylazo)benzene 3a could only be
cyano-substituted derivative 3a, a yield of 20% was achieved, marginally isomerized.
whereas the methoxy derivative 3b could be isolated in a good
yield of 59%.
To get deeper insight into the photoisomerization, 1H NMR
spectroscopy was applied to monitor the isomerization process.
Having both tris(arylazo)benzenes 3a/3b in hand, UV–vis spec- For both 3a and 3b, complex spectra were obtained after irradi-
troscopy was used for preliminary investigations on the photo- ation at 365 nm (see Figure S2 and Figure S3, Supporting Infor-
physical properties of the molecular triple switches 3. Both mation File 1). Hence, a high number of photoisomers was
tris(arylazo)benzenes 3a and 3b showed characteristic UV–vis generated, which indicated that selective photoisomerization
spectra of ABs with strong π–π* absorption, having their was not possible in both cases under the applied conditions.
absorption maxima at 337 nm (3a) and 349 nm (3b), respective- After irradiating the samples with light of 448 nm wavelength
ly (Figure 2a). In contrast to AB, the π–π* and n–π* bands of and keeping them in the dark at room temperature, the initial
both compounds overlapped, forming shoulders at ca. 450 nm. spectra could be restored.
The samples were irradiated at 365 nm with a high-power LED
(see Supporting Information File 1 for specifications) to induce Conclusion
E-to-Z photoisomerization.
In summary, 1,3,5-tris(arylazo)benzenes 3a/3b were successful-
ly synthesized using Pd-catalyzed coupling reactions of arylhy-
For the cyano-substituted tris(arylazo)benzene species 3a, the drazides and aryl bromides followed by CuI-mediated oxida-
π→π* absorption band decreased only to a relatively small tion as key steps. Although the low yield of the first coupling
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Beilstein J. Org. Chem. 2020, 16, 22–31.
Figure 2: a) UV–vis spectra of tris(arylazo)benzenes 3a/3b in ethanol. b) Reversible photoisomerization of 3a and c) 3b using light of 365 nm wave-
length to induce E→Z isomerization and of 448 nm wavelength for photochemical back-conversion.
step, due to the preference for double coupling, was a draw- opened an easy access to other analogous to further study the
back of this strategy, enough material could be prepared via this fundamental properties of 1,3,5-tris(arylazo)benzenes in the
method to characterize and investigate the isomerization proper- near future. These new insights will foster the design of novel,
ties of the triple photoswitches 3a/3b. Changing the N-Boc-N- multi-state photoresponsive systems for smart materials.
phenylhydrazides used herein to different derivatives opened
Experimental
the possibility to synthesize a wide variety of unsymmetrical
starazo species, starting from suitable dibromoazobenzenes.
3,5-Dibromo-2′,4′,6′-trimethoxyazobenzene (15) [24]: 3,5-
Dibromoaniline (9.99 g, 39.8 mmol, 1.00 equiv) was suspended
A preliminary investigation of the presented three-state in water (20 mL) and aq HBF4 (50%, 15 mL, 119 mmol,
switches by UV–vis and 1H NMR spectroscopy revealed that 3.0 equiv) was added. The suspension was cooled to 0 °C and a
both derivatives 3a and 3b were capable of E→Z photoisomer- solution of NaNO2 (2.76 g, 40.0 mmol, 1.00 equiv) in water
ization. However, no selective photoswitching could be (8 mL) was added dropwise. The grey suspension was vigor-
achieved due to overlapping absorption bands of all arylazoben- ously stirred at 0 °C for 45 min. The precipitate was filtered off,
zene moieties (see Figure 2). Furthermore, analyses showed that washed with Et2O (5 × 50 mL), and dried in vacuum to yield
starazo compound 3b had a higher E/Z ratio in the PSS com- the diazonium tetrafluoroborate as grey solid (11.2 g). To a
pared to derivative 3a. In addition, complex spectra were ob- suspension of this diazonium tetrafluoroborate (11.2 g,
tained, in which the individual isomers could not be assigned 32.0 mmol, 1.00 equiv) in MeOH (80 mL), a solution of 1,3,5-
unambiguously. Although the starazo species that were pre- trimethoxybenzene (5.98 g, 35.6 mmol, 1.11 equiv) in MeOH
pared did not show selective switching, the presented synthesis (80 mL) was added dropwise at rt over 15 min. After standing
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Beilstein J. Org. Chem. 2020, 16, 22–31.
overnight at −20 °C, the orange precipitate was filtered off, tert-Butyl (E)-2-(3-(2-(tert-butoxycarbonyl)-2-(4-cyano-
washed with cold MeOH (ca. 25 mL), and dried in vacuum to phenyl)hydrazinyl)-5-((2,4,6-trimethoxyphenyl)-
yield 15 as orange powder (13.8 g, 80%). mp 213–215 °C (dec); diazenyl)phenyl)-1-phenylhydrazine-1-carboxylate (17a): In
1H NMR (400 MHz, DMSO) δ 7.91 (t, J = 1.8 Hz, 1H), 7.80 (d, a nitrogen-filled glovebox, an oven-dried Schlenk tube was
J = 1.8 Hz, 2H), 6.38 (s, 2H), 3.89 (s, 3H), 3.83 (s, 6H); charged with P(t-Bu)3 (2.2 µL, 8.9 µmol, 5.2 mol %). The
13C NMR (101 MHz, DMSO) δ 163.6, 155.6, 155.2, 133.8, following operations were carried out in a fume hood under
126.2, 123.5, 123.1, 91.5, 56.3, 55.8; HRESIMS (m/z): Schlenk conditions. To the Schlenk tube, 16a (100 mg,
[M + H]+ calcd for C15H1579Br2N2O3, 428.9444; found, 172 µmol, 1.00 equiv), N-Boc-N-phenylhydrazine (110 mg,
428.9448.
528 µmol, 3.08 equiv), Pd(OAc)2 (2 mg, 9 µmol, 5 mol %), and
Cs2CO3 (170 mg, 522 µmol, 3.04 equiv) were added. After the
tert-Butyl (E)-2-(3-bromo-5-((2,4,6-trimethoxy- addition of dry toluene (1.7 mL), the mixture was stirred at rt
phenyl)diazenyl)phenyl)-1-(4-cyanophenyl)hydrazine-1- for 30 min. Then, the tube was sealed, and the mixture was
carboxylate (16a): In a nitrogen-filled glovebox, an oven-dried heated to 110 °C for 2 d. After cooling to rt, the mixture was
Schlenk tube was charged with a 1.61 M solution of P(t-Bu)3 filtered through a plug of silica gel using EtOAc, and the filtrate
(395 µL, 636 µmol, 15 mol %) in dry toluene. All following was concentrated. The crude mixture was separated by two
operations were carried out in a fume hood under Schlenk consecutive flash column chromatography steps (SiO2,
conditions. tert-Butyl 1-(4-cyanophenyl)hydrazine-1-carboxyl- cyclohexane/EtOAc, 1:1, v/v, then SiO2, toluene/EtOAc, 5:1 to
ate (1.00 g, 4.25 mmol, 1.00 equiv), 15 (1.82 g, 4.24 mmol, 3:1, v/v) to yield 17a as red oil (mixture of isomers, 28 mg,
1.00 equiv), Pd(OAc)2 (144 mg, 629 µmol, 15 mol %), and 23%). The product was used without further purification. See
Cs2CO3 (2.11 mg, 6.40 mmol, 1.51 equiv) were added and Supporting Information File 1 for the 1H NMR spectrum.
suspended in dry toluene (42 mL). After stirring at rt for HRESIMS: [M + H]+ calcd for C38H44N7O7, 710.3302; found,
35 min, the tube was sealed and heated to 110 °C for 3.5 h. 710.3427.
After cooling to rt, the mixture was filtered through a plug of
silica gel using EtOAc and concentrated. The mixture was tert-Butyl (E)-2-(3-(2-(tert-butoxycarbonyl)-2-(4-methoxy-
separated by flash column chromatography (SiO2, phenyl)hydrazinyl)-5-((2,4,6-trimethoxyphenyl)-
cyclohexane/EtOAc, 2:1, v/v) to yield 16a as red solid (mixture diazenyl)phenyl)-1-phenylhydrazine-1-carboxylate (17b): In
of isomers, 248 mg, 10%). The product was used without a nitrogen-filled glovebox, an oven-dried Schlenk tube was
further purification. See Supporting Information File 1 for the charged with P(t-Bu)3 (9.5 µL, 37 µmol, 15 mol %). All
1H NMR spectrum. HRESIMS (m/z): [M + Na]+ calcd for following operations were carried out in a fume hood under
C27H2879BrN5O5Na, 604.1166; found, 604.1167.
Schlenk conditions. To the Schlenk tube, 16b (150 mg,
255 µmol, 1.00 equiv), N-Boc-N-phenylhydrazine (164 mg,
tert-Butyl (E)-2-(3-bromo-5-((2,4,6-trimethoxy- 787 µmol, 3.08 equiv), Pd(OAc)2 (9 mg, 39 µmol, 15 mol %),
phenyl)diazenyl)phenyl)-1-(4-methoxyphenyl)hydrazine-1- Cs2CO3 (255 mg, 783 µmol, 3.07 equiv), and dry toluene
carboxylate (16b): In a nitrogen-filled glovebox, an oven-dried (2.5 mL) were added. The mixture was stirred at rt for 30 min.
Schlenk tube was charged with P(t-Bu)3 (155 µL, 628 µmol, Then, the tube was sealed and the mixture was heated to 110 °C
15 mol %). All following operations were carried out in a fume for 24 h. After cooling to rt, the solution was purified by flash
hood under Schlenk conditions. Compound 15 (1.80 g, column chromatography (SiO2, cyclohexane/EtOAc, 2:1, v/v)
4.19 mmol, 1.00 equiv), tert-butyl 1-(4-methoxyphenyl)- to yield 17b as red oil (mixture of isomers, 94 mg, 52%), and
hydrazine-1-carboxylate (1.04 g, 4.36 mmol, 1.04 equiv), the product was used without further purification. See Support-
Pd(OAc)2 (145 mg, 633 µmol, 15.1 mol %), and Cs2CO3 ing Information File 1 for the 1H NMR spectrum. HRESIMS
(2.07 g, 6.29 mmol, 1.5 equiv) were added and suspended in (m/z): [M + Na]+ calcd for C38H46N6O8Na, 737.3269; found,
dry toluene (42 mL). The mixture was stirred at rt for 30 min 737.3269.
and the tube was sealed and heated to 110 °C for 2 d. After
cooling to rt, the reaction mixture was filtered through a plug of (E)-1-(4-Cyanophenyl)-2-(3-((E)-phenyldiazenyl)-5-((E)-
silica gel using EtOAc, concentrated, and the residue was (2,4,6-trimethoxyphenyl)diazenyl)phenyl)diazene (3a): In a
separated by flash column chromatography (SiO2, dry Schlenk tube under a nitrogen atmosphere, to 17a (28 mg,
cyclohexane/EtOAc, 2:1, v/v) to yield 16b as red oil (mixture of 39 µmol, 1.00 equiv) in dry DMF (1 mL) were added CuI
isomers, 218 mg, 9%). The product was used without further (60.0 mg, 313 µmol, 8.0 equiv) and Cs2CO3 (103 mg,
purification. See Supporting Information File 1 for the 1H NMR 316 µmol, 8.0 equiv). The tube was sealed and heated to 140 °C
spectrum. HRESIMS (m/z): [M + H]+ calcd for for 3 h, cooled to rt, and filtered through a plug of silica gel
C27H3279BrN4O6, 587.1500; found, 587.1486.
using EtOAc. The residue was purified by flash column chro-
29

Beilstein J. Org. Chem. 2020, 16, 22–31.
ORCID® iDs
matography (SiO2, cyclohexane/EtOAc, 2:1, v/v) to yield a red
solid (4 mg, 20%), which was recrystallized by slow evapora-
tion from CH2Cl2 in the dark to yield the all-E-isomer 3a.
1H NMR (400 MHz, CDCl3) δ 8.56 (t, J = 1.9 Hz, 1H), 8.53 (d,
J = 1.9 Hz, 2H), 8.11–8.03 (m, 2H), 8.03–7.97 (m, 2H),
7.88–7.83 (m, 2H), 7.61–7.50 (m, 3H), 6.27 (s, 2H), 3.94 (s,
6H), 3.92 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 163.3, 155.9,
155.8, 154.5, 154.3, 154.0, 153.6, 152.6, 149.5, 133.4, 131.8,
129.4, 129.3, 127.7, 123.8, 123.3, 120.0, 119.0, 118.6, 117.7,
114.5, 91.6, 90.7, 56.7, 55.7; HRESIMS (m/z): [M + H]+ calcd
for C28H24N7O3, 506.1935; found, 506.1935.
Andreas H. Heindl - https://orcid.org/0000-0002-5403-2177
Hermann A. Wegner - https://orcid.org/0000-0001-7260-6018
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(E)-1-(4-Methoxyphenyl)-2-(3-((E)-phenyldiazenyl)-5-((E)-
(2,4,6-trimethoxyphenyl)diazenyl)phenyl)diazene (3b): A
dry Schlenk tube under nitrogen atmosphere was charged with a
solution of 17b (78 mg, 109 µmol, 1.00 equiv), CuI (167 mg,
873 µmol, 8.0 equiv), Cs2CO3 (284 mg, 872 µmol, 8.0 equiv),
and dry DMF (2.8 mL). The tube was sealed and heated to
140 °C for 17.5 h. After cooling to rt, the mixture was filtered
through a plug of silica gel using EtOAc, and separated by two
consecutive purification steps by flash column chromatography
(SiO2, cyclohexane/EtOAc, 2:1, v/v) to yield 3b as red oil
(33 mg, 59%). The all-E-isomer was obtained by recrystalliza-
tion through slow evaporation from CHCl3 in the dark.
1H NMR (400 MHz, CDCl3) δ 8.49 (s, 3H), 8.03–7.98 (m, 4H),
7.60–7.47 (m, 3H), 7.04 (d, J = 8.9 Hz, 2H), 6.26 (s, 2H), 3.93
(s, 6H), 3.91–3.89 (m, 6H); 13C NMR (101 MHz, CDCl3)
δ 162.9, 162.6, 155.6, 155.3, 155.0, 154.1, 154.0, 153.6, 152.7,
147.1, 131.5, 129.3, 127.8, 125.2, 125.0, 123.2, 118.7, 118.2,
117.3, 116.2, 114.4, 91.6, 56.7, 55.7, 55.7; HRESIMS (m/z):
[M + H]+ calcd for C28H27N6O4, 511.2089; found, 511.2089.
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doi:10.1021/ol0168216
Supporting Information File 1
Additional synthetic procedures, isomerization
experiments, and 1H/13C NMR spectra.
[https://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-16-4-S1.pdf]
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Acknowledgements
The authors thank Elena M. Berger and Katinka Grimmeisen
for their help in the synthesis of starting materials and interme-
diates. Lea Schäfer is acknowledged for helping in the design of
the TOC figure.
24.Hansen, M. J.; Lerch, M. M.; Szymanski, W.; Feringa, B. L.
Angew. Chem., Int. Ed. 2016, 55, 13514–13518.
Funding
Financial support by the Deutsche Forschungsgemeinschaft
(DFG; WE 5601/6-1) is gratefully acknowledged.
doi:10.1002/anie.201607529
30

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