Synthesis of functionalized azobiphenyls and azoterphenyls with improved solubilities for switching applications

Article abstract of DOI:10.1055/s-0033-1339028

Nine new azo compounds, in particular azobiphenyls and azoterphenyls, have been synthesized and their photochemical switching has been investigated. 4,4′-Dihalogenated azobenzenes were generated by oxidative copper-mediated coupling of respective anilines followed by Suzuki-Miyaura cross-coupling reaction. The elongated azobenzenes carry functional groups at the terminal 4-positions and additional methyl substituents at the central benzene rings. While the introduction of two methyl groups improved the solubility of the resulting azo compounds considerably, the introduction of four methyl groups was less successful with respect to solubility. Differences were also found in the photochemical behavior for the dimethyl and the tetramethyl derivatives. Georg Thieme Verlag Stuttgart. New York.

Full text of DOI:10.1055/s-0033-1339028

2376▌
PAPER
pSapyenr thesis of Functionalized Azobiphenyls and Azoterphenyls with Improved
Solubilities for Switching Applications
Elongated Azoarenes
Isabel Köhl, Ulrich Lüning*
Christian-Albrechts-Universität zu Kiel, Otto-Diels-Institut für Organische Chemie, Olshausenstr. 40, 24098 Kiel, Germany
Fax +49(431)8801558; E-mail: luening@oc.uni-kiel.de
Received: 09.01.2014; Accepted after revision: 07.04.2014
Already in 1937, the reversible switching of azobenzene
by light was described by Hartley, and azobenzene deriv-
Abstract: Nine new azo compounds, in particular azobiphenyls and
azoterphenyls, have been synthesized and their photochemical
switching has been investigated. 4,4′-Dihalogenated azobenzenes
2
atives have become the work horse of switching by light
3
,4
were generated by oxidative copper-mediated coupling of respec- and resulting mechanical work, for instance, the switch-
tive anilines followed by Suzuki–Miyaura cross-coupling reaction. ing in a polymer film which leads to a macroscopic defor-
5
,6
The elongated azobenzenes carry functional groups at the terminal
-positions and additional methyl substituents at the central ben-
mation of the film.
4
Azobenzenes can be switched from the thermodynamical-
ly stable E-form to the Z-form upon irradiation with UV-
zene rings. While the introduction of two methyl groups improved
the solubility of the resulting azo compounds considerably, the in-
troduction of four methyl groups was less successful with respect to light (ca. 365 nm). The thermodynamically less stable Z-
solubility. Differences were also found in the photochemical behav- form can isomerize back to the more stable E-form either
ior for the dimethyl and the tetramethyl derivatives.
thermally or upon irradiation with visible light (ca. 440
Key words: azo compounds, cross-coupling, isomerization, photo- nm). During this process, the distance between the termi-
chemistry, switching
nal positions of an azobenzene is reduced by ca. 0.35 nm.
Scheme 1 shows that introduction of additional benzene
rings, that is, the use of azobiphenyl compounds instead of
Controlled mechanical motion is not only central to tech- the parent azobenzene derivatives, leads to a larger differ-
nology in the macroscopic world but also a crucial part of ence of the distance between the terminal positions in the
biological systems on the molecular scale. Consequently, E- and Z-isomers.
controlled molecular motion and molecular switches have
In order to exploit the length change upon irradiation, the
come into the focus of research at the turn of the millenni-
terminal positions of an azo compound must carry reac-
1
um. Numerous stimuli are imaginable: chemical input
tive functional groups in order to connect the switch with
such as pH changes, redox potential, or light. The charm
the rest of the molecular machine. Often, carboxylic acids
of the latter lies in its easy handling and the contact-free
are used, and consequently the most simple elongated azo
interaction with the system to be switched.
7
compound is azobiphenyl-4′′,4′′′-dicarboxylic acid. Un-
fortunately, this molecule is only scarcely soluble in most
R
R
Δ L2
1
or 2
Δ L1
R
R
N
hν
LE1
N
hν
1
or 2
hν or Δ
N
LE2
N
N
LZ1
hν or Δ
N
N
N
R
LZ2
R
1
or 2
R
1 or 2
R
Scheme 1 Upon irradiation, E-azo compounds are isomerized into their respective Z-isomers. The length change ΔL (ΔL –ΔL ) increases with
E
Z
each incorporated aromatic ring from ΔL1 = ca. 0.35 nm for azobenzene to ΔL2 = ca. 1 nm for azoterphenyl.
SYNTHESIS 2014, 46, 2376–2382
Advanced online publication: 22.05.2014
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0033-1339028; Art ID: ss-2014-t0023-op
Georg Thieme Verlag Stuttgart · New York
©

PAPER
Elongated Azoarenes
2377
solvents. It is highly probable that related azoterphenyls tramethyl azobiphenyldicarboxylate 5c could be obtained
are even less soluble. However, solubilities of azobiphe- from dibromide 3c (Scheme 2).
nyls can be enhanced by substitution of the aryl rings.
Besides these azobiphenyls 5 and 6, also azoterphenyls 8
Thus, tetramethoxy-substituted azobiphenyl derivatives
and 9 were synthesized by Suzuki–Miyaura cross-cou-
8
have been described and also methyl groups have been
plings. First, the iodinated azobenzene 4b was coupled
introduced.9
with 4-bromophenylboronic acid to give dibromoazobi-
For the synthesis of more soluble elongated azo com- phenyl 7 in 90% yield. By a second cross coupling em-
pounds or even azoterphenyl derivatives, we have intro- ploying an ester- or an aldehyde-substituted boronic acid,
duced methyl groups in different numbers and positions azoterphenyls 8 and 9 were generated in 41 and 60%
into azobiphenyl and azoterphenyl derivatives.
yield, respectively (Scheme 3).
Syntheses of azobenzenes were carried out using the oxi- All new halogenated azobiphenyls and azoterphenyls
10
dative copper-catalyzed dimerization of anilines. Start- showed good solubilities in organic solvents. In compari-
ing from halogenated anilines 1 or 2, respective bromo- or son, the introduction of only two methyl groups and not
iodoazobenzenes 3 and 4 could be obtained in moderate to four led to better solubility. The relative solubilities of 3b
good yields for all cases in which methyl groups did not with respect to 3c or 5b with respect to 5c were 4:1 and
occupy a position ortho to the amino group (d) (Scheme 2.5:1, respectively, in CDCl at room temperature. One
3
2
).
reason for the improved solubility of the less substituted
compounds can be their larger unsymmetry. By rotation
along one bond between an azo nitrogen atom and an ad-
jacent benzene ring, a 180° turn generates an identical
conformer for tetramethylated compounds while such a
rotation will produce a new conformer in the case of di-
methyl derivatives. In total, there will be three times as
many conformers in the dimethylated compounds, and ac-
cordingly the solubility will be increased due to a smaller
concentration of each conformer. In addition, there is also
The 4,4′-dihalogenated azobenzenes 3b and 3c were then
elongated by Suzuki–Miyaura cross-coupling reactions
with phenylboronic acid derivatives yielding methylated
azobiphenyls 5 and 6 with ester or aldehyde functional-
ities, respectively. Starting from 3,3′-dimethyl-4,4′-dibro-
moazobenzene (3b), azobiphenyldicarboxylate 5b and
azobiphenyldicarbaldehyde 6b were obtained in 78 and
4
1% yield, respectively. Analogously, a respective te-
R1
Hal
NH2
R1
R2
R4
R3
(HO)2B
R2
R3
CuCl, pyridine, O2
R4
R3
R3
N
N
N
R4
N
R2
R1
Pd(PPh3)4, NaHCO3
DMF–toluene–H2O
R3
R2
R2
X
R1
1
X = Br, 2 X = I
X
R1
R4 = CO2Me
6 R4 = CHO
–
41%
–
5
R1 R2 R3
H
Me H
a
b
c
d
–
3
X = Br
79%
89%
79%
–
4 X = I
69%
48%
–
a
b
c
d
H
H
H
78%
12%
–
a
b
c
d
Me Me H
Me
–
H
H
3%
Scheme 2 Oxidative dimerization of anilines 1 and 2 to give halogenated azobenzenes 3a–c and 4a,b and 4d. Suzuki–Miyaura cross-coupling
of 3 and 4 with boronic acids yielded azobiphenyls 5b and 5c and 6b with enhanced solubility.
(
HO)2B
Br
(HO)2B
R
N
Br
4b
Br
N
Pd(PPh3)4, CsF, THF
Pd(PPh3)4, NaHCO3
DMF–toluene–H2O
7
90%
N
R
R
N
8
9
R = CO2Me 41%
R = CHO 60%
Scheme 3 Employing Suzuki–Miyaura cross-couplings with two different boronic acid building blocks, the halogenated azobenzene 4b was
converted into the soluble azoterphenyls 8 and 9.
©
Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 2376–2382

2378
I. Köhl, U. Lüning
PAPER
a kinetic aspect: the (re)crystallization process is slowed Since Z- and E-isomers display two distinguishable sets of
down considerably because all molecules have to adopt a signals in the aromatic region of the proton NMR spectra,
proper conformation first.
integrations of these resonances were used to determine
the E/Z-isomer ratios.
Next, the photochemistry of the new, elongated azo com-
pounds 5–9 was investigated and compared to that of As a typical example, Figure 2 shows the development of
known1 and the yet unknown azobenzenes 3 and 4. The the signals in the aromatic region of azobiphenyl 6b when
E,Z-isomerization of these simpler model compounds 3a–c irradiated at 365 nm for 30 minutes and then left unirradi-
and 4a,b and 4d, and of the longer azobiphenyls 5–7 and ated. The decrease in the intensity of the signals of the Z-
azoterphenyls 8 and 9 was investigated in solution using isomer (red) with time (upper three spectra, from bottom
NMR and UV/Vis spectroscopy. For photochemical en- to top) is clearly visible. Irradiation for 30 minutes also
richment of one of the two stereoisomers, the wavelength switched the other investigated azoarenes from E to Z. Af-
of irradiation had to be selected carefully in order to avoid ter the irradiation was stopped, the signals for the E-iso-
1–14
15
photochemical back isomerization. Preferred formation mer increased again with time. Respective half-life times
of Z-isomers was achieved by irradiation with light of 365 t1/2 of thermal back isomerization were determined at
nm, since at this wavelength the E-isomer absorbs almost 20 °C. For this purpose, the azoarenes were first irradiated
exclusively due to a very small extinction coefficient of with 365 nm for 30 minutes, then the decrease of the sig-
the Z-isomer at this wavelength (Figure 1). The reverse nals of the Z-isomers was recorded over a period of one to
isomerization (Z → E) was performed using light with a two days. Thermal back isomerization of azo compounds
1
6,17
wavelength of 440 nm.
is reported to be a first order reaction.
The amounts of
Z-isomers after 30 minutes and their respective half-life
times are summarized in Table 1 for all compounds.
Table 1 Irradiation of Azobenzene Derivativesa
Azobenzene
Z-isomer (%)b
t1/2 (h)c
3
3
3
4
4
4
5
5
a
b
c
89
97
91e
84
92
88
93
87e
89
78
87
77
11d
7
8
a
b
d
b
c
5
15
11
7
3
Figure 1 UV/Vis spectra of dimethyl 2,2′-dimethyl-4,4′-azobiphe-
nyl-4′′,4′′′-dicarboxylate (5b) in toluene upon repeated irradiations
with light of 365 and 440 nm.
6b
7
11d
15
15
28d
Exemplarily, Figure 1 shows the UV/Vis spectra of 5b
upon alternating irradiation with UV and visible light.
Analogously, all other azobenzenes were irradiated with
light of a wavelength of 365 nm for 30 minutes first. The
formation of the Z-isomers could be followed in the spec-
tra by significant decreases in the absorption of the π–π*
transition at about 350 nm and slight increases in the in-
tensities of the n–π* transitions at about 450 nm. In each
8
9
a
Percentage of Z-isomer after 30 min of irradiation and half-life time
t
at 20 °C are listed.
1/2
b
For most compounds, a photostationary state was reached after 5–10
min.
c
Due to errors in integration, t1/2 values are rounded.
In addition to the integration errors, deviations from linearity have
d
case, the E-isomers could be restored by light-induced also been observed. The total error is estimated to be 20–30%.
e
back isomerization upon irradiation at 440 nm. Due to the
fact that the two isomers absorb at both wavelengths, both
switching processes do not take place in 100% yield.
However, also thermal isomerization generates the E-
form if one waits long enough (for half lives, see Table 1).
The isomerization was reversible for all investigated azo-
benzene derivatives.
For yet unknown reasons, the Z-isomer is formed in nonreproducible
quantities. The highest obtained percentages are shown.
The results of Table 1 show that high percentages of Z-
isomers of the azo compounds 3–9 are obtained upon irra-
diation at 365 nm. The introduction of two methyl groups
increased the amount of Z-isomers (3a/3b: 89:97%,
4a/4b: 84:92%). But two more methyl groups, that is, four
methyl groups in total (4c, 5c), had an opposite effect.
Synthesis 2014, 46, 2376–2382
© Georg Thieme Verlag Stuttgart · New York

PAPER
Elongated Azoarenes
2379
Figure 2 Aromatic region of proton NMR spectra of 2,2′-dimethyl-4,4′-azobiphenyl-4′′,4′′′-dicarbaldehyde (6b). The bottom spectrum shows
the unexposed sample as reference. The signals are color-coded for E (blue box) and Z (red background). The second spectrum from the bottom
shows the signals of the sample after irradiation with a wavelength of 365 nm in deuterated toluene for 30 min. The upper three spectra show
a decrease of the intensities of the Z signals over time (from bottom to top).
High percentages of Z-isomers as found for the dimethyl
compounds were never observed, in contrast, the values
listed in Table 1 were difficult to reproduce, and only the
highest observed are listed. The factors which cause the
bad reproducibility of the E/Z-isomerizations of the te-
tramethyl derivatives are yet unknown. But when Z-tetra-
meta-methylazo compounds are compared to less methyl-
ated ones, a steric repulsion between the meta-methyl
groups in the Z-isomers is obvious (Figure 3), which may
destabilize the Z-form but will also lower the activation
barrier of the isomerization.
In conclusion, we were able to synthesize eight new
azoarenes that are soluble in most of the common organic
Figure 3 Visualization of the sterical strain in (Z)-3,3′,5,5,′-te-
solvents. Their solubilities are high enough to carry out
tramethylazobenzene. The ortho-protons and the meta-methyl groups
both contribute to a repulsion, which may facilitate isomerization.
NMR measurements in chloroform and even in toluene.
Remarkably, even a certain solubility in cyclohexane was
observed for some azobiphenyls and azoterphenyls.
measurements comparable to the measurements discussed
above. Nevertheless, diacid 10 is soluble in DMSO in a
concentration which is high enough to carry out NMR
measurements. This solubility will also allow the use of
diacid 10 in subsequent reactions and measurements.
For further experiments, the functional groups of the azo-
biphenyls and azoterphenyls can be used. For example, di-
ester 5b can be saponified with sodium hydroxide to give
diacid 10 (Scheme 4). However, dicarboxylic acid 10 is
not soluble enough in toluene to record NMR and UV/Vis
1
. NaOH, MeOH–H2O
N
CO2Me 2. aq HCl (1 M)
N
CO2H
MeO2C
N
HO2C
N
5b
10 31%
Scheme 4 Deprotection of the dimethylated azobiphenyl 5b leads to azo compound 10 with free carboxylic acids.
©
Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 2376–2382

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I. Köhl, U. Lüning
PAPER
1
3
Unless otherwise noted, all commercially available compounds
were used as provided without further purification. Solvents for
chromatography were distilled prior to use. Column chromatogra-
phy was performed using Merck silica gel 60 (particle size: 0.040–
C NMR (125 MHz, CDCl ): δ = 151.8 (s, C-1,1′), 138.4 (d, C-3,3′,
3
C-5,5′), 124.5 (d, C-2,2′, C-6,6′), 98.1 (s, C-4,4′).
4
,4′-Diiodo-3,3′-dimethylazobenzene (4b)
Prepared from 4-iodo-3-methylaniline (2.50 g, 10.7 mmol); yield:
.19 g (2.58 mmol, 48%); orange solid; mp 135 °C.
0.063 mm). NMR spectra were recorded on Bruker AC 200, ARX
1
300, DRX 500, or AV 600 instruments. Assignments are supported
–
1
by COSY, HSQC, and HMBC. Even when obtained by DEPT, the
IR (ATR): 1556, 1465, 1377, 1025, 889, 817 cm .
1
13
type of C signal is always listed as singlet, doublet, etc. All chem-
ical shifts are given in parts per million and are referenced to TMS
or to the residual proton or carbon signal of the solvent. EI/CI mass
spectra were recorded with a Finnigan MAT 8200 or MAT 8230
spectrometer. MALDI mass spectra were recorded with a Bruker-
Daltonics Biflex III instrument and Cl-CCA (4-chloro-α-cyanocin-
namic acid) as matrix. High-resolution mass spectra were recorded
in the EI mode with a Jeol Accu TOF GCV 4G instrument. IR spec-
tra were recorded on a Perkin-Elmer Paragon 1000/Perkin-Elmer
Spectrum 100 fitted with an MKII Golden GateTM Single Reflec-
tion ATR unit. Elemental analyses were carried out with a Euro EA
H NMR (300 MHz, CDCl ): δ = 7.95 (d, J = 8.4 Hz, 2 H, H-5,5′),
.76 (s, 2 H, H-2,2′), 7.41 (d, J = 8.4 Hz, 2 H, H-6,6′), 2.53 (s, 6 H,
3
7
2
× CH3).
13C NMR (75 MHz, CDCl
139.7 (d, C-5,5′), 123.8 (d, C-2,2′), 121.5 (d, C-6,6′), 104.7 (s, C-
4,4′), 28.1 (q, 2 × CH ).
): δ = 152.4 (s, C-1,1′), 142.6 (s, C-3,3′),
3
3
+•
MS (EI, 70 eV): m/z (%) = 462 (100, [M] ), 217 (93).
Anal. Calcd for C H I N (462.1): C, 36.39; H, 2.62; N, 6.06.
Found: C, 36.70; H, 2.70; N, 5.78.
14 12 2
2
3000 Elemental Analyzer from Euro Vector.
4,4′-Diiodo-2,2′-dimethylazobenzene (4d)
Prepared from 4-iodo-2-methylaniline (2.50 g, 10.7 mmol); yield:
5.0 mg (162 μmol, 3%); brown solid; mp 154 °C.
Azocoupling Reaction; General Procedure
7
A mixture of CuCl (5 g, 50.5 mmol) and pyridine (50 mL) was
stirred at r.t. for 30 min. The suspension was filtered and the halo-
genated aniline (1.5 equiv) was added to the green solution. Air was
bubbled through the solution for 18 h. The residue was diluted with
CH Cl (200 mL) and aq 1 M HCl (100 mL). The aqueous layer was
–
1
IR (ATR): 1575, 1464, 1376, 1182, 858, 817 cm .
1
H NMR (500 MHz, CDCl ): δ = 7.72 (s, 2 H, H-3,3′), 7.59 (d, J =
3
8
2
.3 Hz, 2 H, H-5,5′), 7.32 (d, J = 8.3 Hz, 2 H, H-6,6′), 2.67 (s, 6 H,
× CH3).
2
2
extracted with CH Cl (3 × 100 mL). The combined organic layers
2
2
13C NMR (125 MHz, CDCl
): δ = 150.3 (s, C-1,1′), 140.2 (d, C-
were washed with H O (100 mL), dried (MgSO ), and concentrated.
3
2
4
The crude product was recrystallized from EtOH.
3,3′), 135.7 (d, C-5,5′), 135.1 (s, C-2,2′), 117.6 (d, C-6,6′), 97.9 (s,
C-4,4′), 17.1 (q, 2 × CH3).
4
,4′-Dibromoazobenzene (3a)
+
•
MS (EI, 70 eV): m/z (%) = 462 (36, [M] ), 217 (100).
Prepared from 4-bromoaniline (13.0 g, 75.8 mmol); yield: 10.2 g
1
1
(29.9 mmol, 79%); orange solid; mp 206 °C (Lit. mp 206.7–
Anal. Calcd for C H I N (462.1): C, 36.39; H, 2.62; N, 6.06.
1
4
12 2
2
207.5 °C).
Found: C, 36.48; H, 2.69; N, 5.73.
1
H NMR (500 MHz, CDCl ): δ = 7.79 (d, J = 8.7 Hz, 4 H, H-3,3′,
3
Dimethyl 2,2′-Dimethyl-4,4′-azobiphenyl-4′′,4′′′-dicarboxylate
H-5,5′), 7.65 (d, J = 8.7 Hz, 4 H, H-2,2′, H-6,6′).
(
5b)
13
A solution of 3b (2.00 g, 5.43 mmol), Pd(PPh ) (315 mg, 272 μmol,
C NMR (125 MHz, CDCl ): δ = 151.2 (s, C-1,1′), 132.4 (d, C-3,3′,
3 4
3
5
mol%), 4-methoxycarbonylphenylboronic acid (3.91 g, 21.7
C-5,5′), 125.8 (s, C-4,4′), 124.4 (d, C-2,2′, C-6,6′).
mmol), and NaHCO (2.74 g, 32.6 mmol) in DMF (60 mL), toluene
3
4
,4′-Dibromo-3,3′-dimethylazobenzene (3b)
(45 mL), and H O (75 mL) was heated to reflux for 6 h. After cool-
ing to r.t., the mixture was extracted with EtOAc (3 × 25 mL), the
2
Prepared from 4-bromo-3-methylaniline (6.00 g, 32.2 mmol); yield:
12
5
1
1
.26 g (14.3 mmol, 89%); orange solid; mp 141 °C (Lit. mp
41 °C).
combined organic layers were dried (MgSO ), and the solvents
4
were evaporated. The crude product was purified by chromatogra-
phy (silica gel, CH Cl ); yield: 2.01 g (4.21 mmol, 78%); orange
H NMR (500 MHz, CDCl ): δ = 7.77 (s, 2 H, H-2,2′), 7.66 (d, J =
2
2
3
solid; mp >300 °C.
8.4 Hz, 2 H, H-5,5′), 7.59 (d, J = 8.4 Hz, 2 H, H-6,6′), 2.49 (s, 6 H,
–1
2
× CH3).
IR (ATR): 1717, 1606, 1578, 1516, 1283, 837, 826 cm .
1
3
1
C NMR (125 MHz, CDCl ): δ = 151.5 (s, C-1,1′), 138.9 (s, C-
H NMR (500 MHz, CDCl ): δ = 8.13 (d, J = 8.5 Hz, 4 H, H-3′′,3′′′,
3
3
3
,3′), 133.1 (d, C-5,5′), 128.0 (s, C-4,4′), 124.9 (d, C-2,2′), 121.6 (d,
H-5′′,5′′′), 7.87 (s, 2 H, H-3,3′), 7.83 (d, J = 8.1 Hz, 2 H, H-5,5′),
7.46 (d, J = 8.5 Hz, 4 H, H-2′′,2′′′, H-6′′,6′′′), 7.39 (d, J = 8.1 Hz, 2
H, H-6,6′), 3.96 (s, 6 H, 2 × OCH ), 2.38 (s, 6 H, 2 × CH ).
C-6,6′), 23.0 (q, 2 × CH3).
3
3
4
,4′-Dibromo-3,3′,5,5′-tetramethylazobenzene (3c)
13
1
8
C NMR (125 MHz, CDCl ): δ = 167.0 (s, C=O), 152.2 (s, C-4,4′),
3
Prepared from 4-bromo-3,5-dimethylaniline (1.00 g, 5.00 mmol);
1
3
145.9 (s, C-1′′,1′′′), 143.6 (s, C-1,1′), 136.4 (s, C-2,2′), 130.5 (d, C-
6
1
yield: 782 mg (1.98 mmol, 79%); orange solid; mp 187 °C (Lit.
mp 185–188 °C).
,6′), 129.6 (d, C-2′′,2′′′, C-6′′,6′′′), 129.2 (d, C-3′′,3′′′, C-5′′,5′′′),
29.1 (s, C-4′′,4′′′), 124.8 (d, C-3,3′), 120.5 (d, C-5,5′), 52.2 (q, 2 ×
1
H NMR (300 MHz, CDCl ): δ = 7.62 (s, 4 H, H-2,2′, H-6,6′), 2.51
s, 12 H, 4 × CH3).
3
OCH ), 20.6 (q, 2 × CH ).
3
3
(
+
•
MS (EI, 70 eV): m/z (%) = 478 (50, [M] ), 225 (100), 166 (41).
13
C NMR (75 MHz, CDCl ): δ = 150.8 (s, C-1,1′), 139.3 (s, C-3,3′,
3
Anal. Calcd for C H N O (478.5): C, 75.30; H, 5.48; N, 5.85.
C H N O ·⅓CH Cl : C, 71.88; H, 5.30; N, 5.53. Found: C, 71.95;
H, 5.21; N, 5.79.
C-5,5′), 130.6 (s, C-4,4′), 122.1 (d, C-2,2′, C-6,6′), 24.0 (q, 4 ×
CH3).
30 26
2
4
30 26
2
4
2
2
4
,4′-Diiodoazobenzene (4a)
Prepared from 4-iodoaniline (10.0 g, 45.7 mmol); yield: 6.86 g
Dimethyl 2,2′,6,6′-Tetramethyl-4,4′-azobiphenyl-4′′,4′′′-dicar-
boxylate (5c)
1
4
(15.8 mmol, 69%); orange-red solid; mp 242 °C (Lit. mp 232–
A solution of 3c (1.50 g, 3.78 mmol), Pd(PPh ) (219 mg, 189 μmol,
240 °C).
3 4
5
mol%), 4-methoxycarbonylphenylboronic acid (2.72 g, 15.1
1
H NMR (500 MHz, CDCl ): δ = 7.87 (d, J = 8.5 Hz, 4 H, H-3,3′,
3
mmol), and NaHCO (1.91 g, 22.7 mmol) in DMF (30 mL), toluene
3
H-5,5′), 7.64 (d, J = 8.5 Hz, 4 H, H-2,2′, H-6,6′).
(
30 mL), and H O (60 mL) was heated to reflux for 6 h. After cool-
2
ing to r.t., the mixture was extracted with EtOAc (3 × 25 mL), the
Synthesis 2014, 46, 2376–2382
© Georg Thieme Verlag Stuttgart · New York

PAPER
Elongated Azoarenes
2381
79
combined organic layers were dried (MgSO ), and the solvents
HRMS (EI): m/z calcd for C H Br N : 517.9993; found:
4
26 20
2
2
were evaporated. The crude product was purified by chromatogra-
517.9998.
phy (silica gel, CH Cl ); yield: 221 mg (437 μmol, 12%); orange
solid; mp >300 °C.
2
2
Dimethyl 2,2′-Dimethyl-4,4′-azoterphenyl-4′′′′,4′′′′′-dicarbox-
ylate (8)
–
1
IR (ATR): 1717, 1609, 1559, 1480, 1094, 846, 826 cm .
A solution of 7 (2.82 g, 5.43 mmol), Pd(PPh ) (315 mg, 272 μmol,
3
4
1
5 mol%), 4-methoxycarbonylphenylboronic acid (3.91 g, 21.7
H NMR (500 MHz, CDCl ): δ = 8.15 (d, J = 8.6 Hz, 4 H, H-3′′,3′′′,
3
mmol), and NaHCO (2.74 g, 32.6 mmol) in DMF (60 mL), toluene
H-5′′,5′′′), 7.69 (s, 4 H, H-3,3′, H-5,5′), 7.28 (d, J = 8.6 Hz, 4 H, H-
3
(
45 mL), and H O (75 mL) was heated to reflux for 6 h. After cool-
2
′′,2′′′, H-6′′,6′′′), 3.97 (s, 6 H, 2 × OCH ), 2.12 (s, 6 H, 2 × CH ).
2
3
3
ing to r.t., the mixture was diluted with H O (25 mL) and EtOAc (25
13
2
C NMR (125 MHz, CDCl ): δ = 167.0 (s, C=O), 151.9 (s, C-4,4′),
3
mL). The layers were separated and the aqueous layer was extracted
with CH Cl (3 × 100 mL). The organic layers were combined and
1
45.5 (s, C-1′′,1′′′), 143.6 (s, C-1,1′), 136.8 (s, C-2,2′, C-6,6′), 129.9
2
2
(d, C-2′′,2′′′, C-6′′,6′′′), 129.2 (s, C-4′′,4′′′), 129.0 (d, C-3′′,3′′′, C-
the precipitated solid was collected by filtration; yield: 1.39 g (2.20
mmol, 41%); orange solid; mp >300 °C.
5
′′,5′′′), 121.8 (d, C-3,3′, C-5,5′), 52.2 (q, 2 × OCH ), 20.9 (q, 2 ×
3
CH3).
IR (ATR): 1716, 1605, 1435, 1393, 1277, 1112, 1101, 1006, 829,
+
•
MS (EI, 70 eV): m/z (%) = 506 (38, [M] ), 239 (100), 180 (20).
–1
7
73 cm .
Anal. Calcd for C H N O (506.6): C, 75.87; H, 5.97; N, 5.53.
1
3
2
30
2
4
H NMR (500 MHz, CDCl ): δ = 8.15 (d, J = 8.4 Hz, 4 H, H-
′′′′,3′′′′′, H-5′′′′,5′′′′′), 7.89 (s, 2 H, H-3,3′), 7.85 (d, J = 8.3 Hz, 2 H,
3
C H N O ·½ H O: C, 74.54; H, 6.06; N, 5.43. Found: C, 74.46; H,
3
2
30
2
4
2
3
5.99; N, 5.21.
H-5,5′), 7.75 (d, J = 8.4 Hz, 4 H, H-2′′,2′′′, H-6′′,6′′′), 7.73 (d, J =
8
2
2
.4 Hz, 4 H, H-3′′,3′′′, H-5′′,5′′′), 7.50 (d, J = 8.4 Hz, 4 H, H-
′′′′,2′′′′′, H-6′′′′,6′′′′′), 7.45 (d, J = 8.3 Hz, 2 H, H-6,6′), 3.96 (s, 6 H,
× OCH ), 2.45 (s, 6 H, 2 × CH ).
2
,2′-Dimethyl-4,4′-azobiphenyl-4′′,4′′′-dicarbaldehyde (6b)
A solution of 3b (2.00 g, 5.43 mmol), Pd(PPh ) (315 mg, 272 μmol,
3
4
5
mol%), 4-formylphenylboronic acid (3.36 g, 21.7 mmol), and
3
3
13
NaHCO (2.74 g, 32.6 mmol) in DMF (60 mL), toluene (45 mL),
and H O (75 mL) was heated to reflux for 6 h. After cooling to r.t.,
the mixture was extracted with CH Cl (3 × 25 mL), the combined
organic layer were dried (MgSO ), and the solvents were evaporat-
ed. The crude product was purified by chromatography (silica gel,
CH Cl ); yield: 940 mg (2.25 mmol, 41%); orange solid; mp
C NMR (125 MHz, CDCl ): δ = 167.0 (s, C=O), 152.0 (s, C-4,4′),
3
3
2
145.2 (s, C-1′′′′,1′′′′′), 144.0 (s, C-1,1′), 141.1 (s, C-1′′,1′′′), 138.9 (s,
C-4′′,4′′′), 136.5 (s, C-2,2′), 130.7 (d, C-6,6′), 130.2 (d, C-3′′′′,3′′′′′,
C-5′′′′,5′′′′′), 129.7 (d, C-2′′′′,2′′′′′, C-6′′′′,6′′′′′), 129.1 (s, C-4′′′′,4′′′′′),
127.1 (d, C-3′′,3′′′, C-5′′,5′′′), 127.0 (d, C-2′′,2′′′, C-6′′,6′′′), 124.8 (d,
C-3,3′), 120.5 (d, C-5,5′), 52.2 (q, 2 × OCH ), 20.7 (q, 2 × CH ).
2
2
4
2
2
3
3
210 °C.
MS (MALDI-TOF, Cl-CCA): m/z = 631 [M + H]+.
–
1
IR (ATR): 1695, 1599, 1381, 1209, 1169, 1003, 821, 748 cm .
Anal. Calcd for C H N O (630.3): C, 79.98; H, 5.43; N, 4.44.
Found: C, 79.22; H, 5.23; N, 4.29.
42
34
2
4
1
H NMR (500 MHz, CDCl ): δ = 10.09 (s, 2 H, CHO), 7.98 (d, J =
3
8
8
7
.3 Hz, 4 H, H-3′′,3′′′, H-5′′,5′′′), 7.89 (s, 2 H, H-3,3′), 7.85 (d, J =
.1 Hz, 2 H, H-5,5′), 7.56 (d, J = 8.3 Hz, 4 H, H-2′′,2′′′, H-6′′,6′′′),
.41 (d, J = 8.1 Hz, 2 H, H-6,6′), 2.40 (s, 6 H, 2 × CH3).
Dimethyl 2,2′-Dimethyl-4,4′-azoterphenyl-4′′′′,4′′′′′-dicarbal-
dehyde (9)
A solution of 7 (1.41 g, 2.72 mmol), Pd(PPh ) (158 mg, 136 μmol,
3
4
13
C NMR (125 MHz, CDCl ): δ = 191.9 (d, CHO), 152.2 (s, C-4,4′),
3
5 mol%), 4-formylphenylboronic acid (1.63 g, 10.9 mmol), and
147.5 (s, C-1′′,1′′′), 143.3 (s, C-1,1′), 136.4 (s, C-2,2′), 135.3 (s, C-
4′′,4′′′), 130.4 (d, C-6,6′), 129.8 (d, C-3′′,3′′′, C-5′′,5′′′), 129.7 (d, C-
2′′,2′′′, C-6′′,6′′′), 124.9 (d, C-3,3′), 120.6 (d, C-5,5′), 20.6 (q, 2 ×
NaHCO (1.37 g, 16.3 mmol) in DMF (30 mL), toluene (30 mL),
3
and H O (40 mL) was heated to reflux for 7 h. After cooling to r.t.,
2
the mixture was diluted with H O (25 mL) and CH Cl (50 mL). The
2
2
2
CH3).
layers were separated and the organic layer was dried (MgSO ) and
4
+
•
MS (EI, 70 eV): m/z (%) = 418 (33, [M] ), 195 (100).
the solvents were evaporated. The crude product was purified by
chromatography (silica gel, CH Cl ); yield: 929 mg (1.63 mmol,
2
2
Anal. Calcd for C H N O (418.2): C, 80.36; H, 5.30; N, 6.69.
Found: C, 80.38; H, 5.32; N, 6.78.
2
8
22
2
2
6
0%); orange solid; mp 228 °C.
–
1
IR (ATR): 1698, 1602, 1383, 1209, 1165, 1036, 1004, 816, 749 cm .
4
′′,4′′′-Dibromo-2,2′-dimethyl-4,4′-azobiphenyl (7)
1
H NMR (500 MHz, CDCl ): δ = 10.10 (s, 2 H, 2 CHO), 7.98 (d, J =
3
A solution of 4b (2.00 g, 4.33 mmol), Pd(PPh ) (149 mg, 129 μmol,
3
4
8
.2 Hz, 4 H, H-3′′′′,3′′′′′, H-5′′′′,5′′′′′), 7.89 (s, 2 H, H-3,3′), 7.85 (d,
J = 8.1 Hz, 2 H, H-5,5′), 7.74 (d, J = 8.5 Hz, 4 H, H-2′′,2′′′, H-
′′,6′′′), 7.56 (d, J = 8.2 Hz, 4 H, H-2′′′′,2′′′′′, H-6′′′′,6′′′′′), 7.51 (d,
J = 8.5 Hz, 4 H, H-3′′,3′′′, H-5′′,5′′′), 7.45 (d, J = 8.1 Hz, 2 H, H-
3
mol%), 4-bromophenylboronic acid (1.91 g, 9.52 mmol), and CsF
(1.97 g, 12.9 mmol) in THF (50 mL) was heated to reflux for 30 h.
6
After cooling to r.t., n-hexane (25 mL) and H O (25 mL) were add-
ed to the mixture. The layers were separated and the aqueous layer
was extracted with CH Cl (3 × 25 mL). The combined organic lay-
ers were dried (MgSO ) and the solvents were evaporated. The
2
6
,6′), 2.40 (s, 6 H, 2 × CH3).
2
2
13
C NMR (125 MHz, CDCl ): δ = 191.9 (d, CHO), 152.2 (s, C-4,4′),
4
3
crude product was purified by chromatography (silica gel, CH Cl );
yield: 2.02 g (3.89 mmol, 90%); orange solid; mp 152 °C.
147.5 (s, C-1′′,1′′′), 146.7 (s, C-1′′′′,1′′′′′), 143.3 (s, C-1,1′), 138.6 (s,
C-4′′,4′′′), 136.4 (s, C-2,2′), 135.3 (s, C-4′′′′,4′′′′′), 130.4 (d, C-6,6′),
129.8 (d, C-3′′′′,3′′′′′, C-5′′′′,5′′′′′), 129.7 (d, C-2′′′′,2′′′′′, C-6′′′′,6′′′′′),
2
2
–
1
IR (ATR): 2919, 1556, 1470, 1384, 1001, 887, 813 cm .
127.6 (d, C-3′′,3′′′, C-5′′,5′′′), 127.2 (d, C-2′′,2′′′, C-6′′,6′′′), 124.9 (d,
1
H NMR (500 MHz, CDCl ): δ = 7.85 (s, 2 H, H-3,3′), 7.80 (d, J =
3
C-3,3′), 120.5 (d, C-5,5′), 20.6 (q, 2 × CH3).
MS (MALDI-TOF, Cl-CCA): m/z = 571 [M + H]+.
8
5
2
.0 Hz, 2 H, H-5,5′), 7.58 (d, J = 8.5 Hz, 4 H, H-3′′,3′′′, H-
′′,5′′′),7.35 (d, J = 8.0 Hz, 2 H, H-6,6′), 7.24 (d, J = 8.5 Hz, 4 H, H-
′′,2′′′, H-6′′,6′′′), 2.37 (s, 6 H, 2 × CH3).
HRMS (EI): m/z calcd for C H N O : 570.2307; found: 570.2280.
40
30
2
2
13
C NMR (125 MHz, CDCl ): δ = 152.0 (s, C-4,4′), 143.4 (s, C-
3
2
,2′-Dimethyl-4,4′-azobiphenyl-4′′,4′′′-dicarboxylic Acid (10)
1
6
3
,1′), 140.1 (s, C-1′′,1′′′), 136.4 (s, C-2,2′), 131.4 (d, C-2′′,2′′′, C-
′′,6′′′), 130.7 (d, C-3′′,3′′′, C-5′′,5′′′), 130.5 (d, C-6,6′), 124.8 (d, C-
,3′), 121.5 (s, C-4′′,4′′′), 120.5 (d, C-5,5′), 20.6 (q, 2 × CH3).
A solution of azobiphenyl 5b (1.50 g, 3.13 mmol) and NaOH (2.50
g, 6.26 mmol, 2 equiv) in MeOH (50 mL) and H O (50 mL) was
2
heated to reflux for 20 h. The reaction mixture was filtered and the
filtrate was acidified to pH 4 with aq 1 M HCl. The precipitated
product was collected by filtration; yield: 441 mg (979 μmol, 31%);
orange solid; mp >300 °C.
+
•
MS (EI, 70 eV): m/z (%) = 520 (15, [M] ), 247 (25), 245 (23), 166
100).
(
©
Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 2376–2382

2382
I. Köhl, U. Lüning
PAPER
1
H NMR (600 MHz, DMSO-d ): δ = 13.05 (s, 2 H, CO H), 8.05 (d,
(2) Hartley, G. S. Nature 1937, 140, 281.
6
2
J = 8.4 Hz, 4 H, H-3′′,3′′′, H-5′′,5′′′), 7.91 (s, 2 H, H-3,3′), 7.83 (d,
J = 8.1 Hz, 2 H, H-5,5′), 7.57 (d, J = 8.4 Hz, 4 H, H-2′′,2′′′, H-
(3) Kumar, G. S.; Neckers, D. C. Chem. Rev. 1989, 89, 1915.
(4) Roy, D.; Cambre, J. N.; Sumerlin, B. S. Prog. Polym. Sci.
2010, 35, 278.
6′′,6′′′), 7.48 (d, J = 8.1 Hz, 2 H, H-6,6′), 2.38 (s, 6 H, 2 × CH3).
–
1
(5) Yu, Y.; Nakano, M.; Ikeda, T. Nature 2003, 425, 145.
IR (ATR): 3006, 1678, 1607, 1276, 1261, 837 cm .
(
6) Yamada, M.; Kondo, M.; Mamiya, J.; Yu, Y.; Kinoshita, M.;
13
C NMR (150 MHz, DMSO-d ): δ = 167.1 (s, C=O), 151.3 (s, C-
6
Barrett, C. J.; Ikeda, T. Angew. Chem. Int. Ed. 2008, 47,
4
4,4′), 144.7 (s, C-1′′,1′′′), 143.4 (s, C-1,1′), 136.4 (s, C-2,2′), 130.7
986; Angew. Chem. 2008, 120, 5064.
7) Okuma, T.; Oishi, Y.; Ito, N. Jpn. Kokai Tokkyo Koho JP
0195034 A 19980728, 1998.
8) Samanta, S.; Beharry, A. A.; Sadovski, O.; McCormick, T.
M.; Babalhavaeji, A.; Tropepe, V.; Woolley, G. A. J. Am.
Chem. Soc. 2013, 135, 9777.
(
(
d, C-6,6′), 129.8 (s, C-4′′,4′′′), 129.3 (d, C-2′′,2′′′, C-6′′,6′′′), 129.2
d, C-3′′,3′′′, C-5′′,5′′′), 124.7 (d, C-3,3′), 120.2 (d, C-5,5′), 20.2 (q,
(
(
1
2
× CH3).
+
•
MS (EI, 70 eV): m/z (%) = 450 (69, [M] ), 330 (18), 211 (100).
Anal. Calcd for C H N O (450.5): C, 74.65; H, 4.92; N, 6.22.
2
8
22
2
4
(
9) Ma, H.; Li, W.; Wang, J.; Xiao, G.; Gong, Y.; Qi, C.; Feng,
Y.; Li, X.; Bao, Z.; Cao, W.; Sun, Q.; Veaceslav, C.; Wang,
F.; Lei, Z. Tetrahedron 2012, 68, 8358.
C H N O ·H O: C, 71.78; H, 5.16; N, 5.98. Found: C, 72.28; H,
2
8
22
2
4
2
4.81; N, 6.09.
(
10) Jousselme, B.; Blanchard, P.; Gallego-Planas, N.; Levillain,
E.; Delaunay, J.; Allain, M.; Richomme, P.; Roncali, J.
Chem. Eur. J. 2003, 9, 5297.
Acknowledgment
Financial support of the DFG (Deutsche Forschungsgemeinschaft,
SFB 677) is gratefully acknowledged.
(
(
(
(
(
11) Kageyama, Y.; Murata, S. J. Org. Chem. 2005, 70, 3140.
12) Corbett, J. F.; Holt, P. F. J. Chem. Soc. 1963, 2385.
13) Wimmer, R.; Müller, N. Monatsh. Chem. 1998, 129, 1161.
14) Kmiecik, J. E. J. Org. Chem. 1965, 30, 2014.
Supporting Information for this article is available online
15) Fischer, E.; Franker, M.; Wolovski, R. J. Chem. Phys. 1955,
at
http://www.thieme-connect.com/products/ejournals/journal/
2
3, 1367.
1
0.1055/s-00000084.SunpfgIpi
o
nr
i
o
(16) Hartley, G. S. J. Chem. Soc. 1938, 633.
(17) Nishimura, N.; Kosako, S.; Sueishi, Y. Bull. Chem. Soc. Jpn.
1
984, 57, 1617.
References
(
18) Kuroyanagi, J.-I.; Kanai, K.; Sugimoto, Y.; Horiuchi, T.;
Achiwa, I.; Takeshita, H.; Kawakami, K. Bioorg. Med.
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Synthesis 2014, 46, 2376–2382
© Georg Thieme Verlag Stuttgart · New York