One-pot preparation of azobenzenes from nitrobenzenes by the combination of an indium-catalyzed reductive coupling and a subsequent oxidation

Article abstract of DOI:10.1016/j.tet.2014.01.048

We demonstrated how a reduction step with a reducing system comprised of In(OTf)₃ and Et₃SiH and a subsequent oxidation that occurred under an ambient (oxygen) atmosphere allowed the highly selective and catalytic conversion of aromatic nitro compounds into symmetrical or unsymmetrical azobenzene derivatives. This catalytic system displayed a tolerance for the functional groups on a benzene ring: an alkyl group, a halogen, an acetyl group, an ester, a nitrile group, an acetyl group, an ester moiety, and a sulfonamide group.

Full text of DOI:10.1016/j.tet.2014.01.048

Tetrahedron 70 (2014) 2027e2033
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Tetrahedron
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One-pot preparation of azobenzenes from nitrobenzenes by the
combination of an indium-catalyzed reductive coupling and
a subsequent oxidation
*
Norio Sakai , Shun Asama, Satsuki Anai, Takeo Konakahara
Department of Pure and Applied Chemistry, Faculty of Science and Technology, Tokyo University of Science (RIKADAI), Noda, Chiba 278-8510, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
We demonstrated how a reduction step with a reducing system comprised of In(OTf)3 and Et3SiH and
a subsequent oxidation that occurred under an ambient (oxygen) atmosphere allowed the highly se-
lective and catalytic conversion of aromatic nitro compounds into symmetrical or unsymmetrical azo-
benzene derivatives. This catalytic system displayed a tolerance for the functional groups on a benzene
ring: an alkyl group, a halogen, an acetyl group, an ester, a nitrile group, an acetyl group, an ester moiety,
and a sulfonamide group.
Received 10 January 2014
Received in revised form 18 January 2014
Accepted 21 January 2014
Available online 25 January 2014
Keywords:
Ó 2014 Elsevier Ltd. All rights reserved.
Azobenzene
Nitrobenzene
Reductive coupling
Indium
Hydrosilane
1. Introduction
Azobenzene derivatives constitute important and central
building blocks in functional materials, as well as in biologically
active substances. For example, aryl azobenzene derivatives, which
emit a variety of colors, have been widely utilized as the coloring
matters, such as azo dyes or pigments, or as the photoresponsive
functional materials, such as liquid crystals.1 Also, because en-
zymes, such as azoreductase are known to selectively metabolize
an azo moiety on azobenzenes for the release of a selected drug,
which may show efficacy as a medicine, an azo moiety is often
embedded in the drug structures.2 Based on this biological action,
sulfasalazine,3 which treats rheumatoid arthritis, and olsalazine,4
which is effective against inflammatory bowel disease, were de-
veloped as prodrugs (Scheme 1). Therefore, the development of
a highly selective preparation for aromatic azobenzenes would be
as valuable as their functions.
The substitution of diazonium salts with electron-rich benzenes
under basic conditions and the coupling reaction of nitro-
sobenzenes with anilines (Mills reaction)5 are considered as the
classical methods that are used to prepare azobenzenes; along with
those, other procedures6 have also been disclosed.7 Recently,
a catalytic oxidation of anilines with a variety of oxidizing reagents,
such as MnO2 (KMnO4),8 KMnO4eCuSO4$5H2O,9 HgOeI2,9a,10 or
Scheme 1. Functional materials containing an azobenzene skeleton.
NaBO3$4H2OeB(OH)3,11 was developed. In their breakthrough
study, Corma and Garcia reported that gold nanoparticles immo-
bilized on TiO2 catalyzed the aerobic oxidative coupling of anilines,
producing azobenzenes.12 Moreover, Jiao and co-workers have re-
ported the development of a Cu(I)epyridine system under an O2
atmosphere, and Shi co-workers have detailed the Cu(I)ediazir-
idinone catalyzed oxidative dehydrogenative coupling of anilines.13
As a reaction system without a metal catalyst, Minakata and co-
workers disclosed that tert-butyl hypoiodite (t-BuOI) promoted
the oxidative dimerization of aromatic amines, leading to a conve-
nient preparation of unsymmetrical azobenzenes.14
* Corresponding author. E-mail address: sakachem@rs.noda.tus.ac.jp (N. Sakai).
0040-4020/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2014.01.048

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N. Sakai et al. / Tetrahedron 70 (2014) 2027e2033
Table 1
Likewise, the preparation of azobenzenes through a reduction of
Examinations of reaction conditions
nitrobenzenes with reducing reagents has also been developed by
several groups, but the typical approach was limited to operations
that required more than stoichiometric amounts of a metal catalyst
either the use of a Zn metal under strong basic conditions15 or the
use of a Pb metal in the presence of HCO2H and Et3N.16 Also,
compared with the catalytic preparation of azobenzenes via the
oxidation of anilines, the catalytic preparation of azobenzenes by
reduction of nitrobenzenes has thus far been limited to specific
procedures using hydrogen gas in the presence of either a nano-Pd,
a Pt-nanowire, a Ru-nanoparticle,17 or another system.18 As far as
we could ascertain, the use of a hydrosilane as a reducing source for
these transformations is unique (Scheme 2). Thus, the development
of a catalytic and simple preparation for azobenzenes via the re-
duction of aromatic nitro compounds seems to have remained
unexplored.
Entry
InX3
Silane
(equiv)
Solv
Yield (%)a
1a
2a
3a
4a
1
2
3
4
5
6
7
8
InBr3
InBr3
InBr3
InBr3
InCl3
In(OAc)3
InBr3
In(OTf)3
In(OTf)3
In(OTf)3
AlCl3
GaCl3
BiCl3
4
4
4
4
4
4
3
3
3
3
4
4
4
4
CHCl3
THF
2
15
96
ND
ND
2
10
Trace
75
94
65
ND
20
25
Trace
Trace
ND
Trace
ND
9
Trace
Trace
ND
19
ND
59
66
(81)
84
ND
3
ND
ND
ND
ND
ND
ND
4
ND
ND
Trace
Trace
ND
3
MeOH
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
48
12
Trace
ND
ND
ND
34
9b
10c
11
12
13
14
ND
ND
ND
ND
ZnCl3
ND
a
GC (Isolated) yield.
b
After the first reduction, the resultant mixture was stirred for 20 h under an
ambient atmosphere.
c
After the first reduction, the resultant mixture was stirred for 3 h under an O2
atmosphere.
further improved both the chemical yield and the product selec-
tivity (entry 8). After several optimizations of the reaction condi-
tions, we finally settled on the following procedure. The mixtures
that involved azobenzene (1a) and hydrazobenzene (3a) that were
produced by the first reduction step, were treated with oxidation
under an ambient atmosphere to directly convert the correspond-
ing azobenzene derivative (entry 9). When the second oxidation
step was carried out under an O2 atmosphere, the reaction time was
drastically shortened (entry 10). During the search for optimal
conditions, we also found that the indium compound catalyzed the
dehydrogenate conversion from a hydrazobenzene to an azo-
benzene.22 However, the use of other group 13 metals, such as AlCl3
and GaCl3, did not catalyze the reduction as well as In(OTf)3, and
neither did ZnCl2 nor BiCl3 (entries 11e14).
With the optimal conditions in hand, the generality of this
coupling was examined using a variety of nitrobenzenes (Table 2).23
The use of a substrate with a methyl group, with no relation to the
location, afforded the desired azobenzene derivatives 1bed in
moderate to good yields. However, when the reaction was carried
out using a nitrobenzene with a methoxy group, the azobenzene 1e
was obtained in only a 10% yield, and most of the starting nitro-
benzene was recovered. This was probably due to the fact that the
indium catalyst coordinated the methoxy group rather than the
nitro group. Unexpectedly, the substrate with a dimethylamino
group produced the azobenzene derivative 1f in a practical yield,
and seemed to more strongly coordinate with the indium catalyst
than the substrate with a methoxy group. The use of nitrobenzenes,
which have a halogen atom and a trifluoromethyl group at the para
position, underwent the coupling reaction to give the correspond-
ing azobenzene derivatives 1gei in relatively good yields. In con-
trast, using nitrobenzenes with an ortho-substituted halogen atom
gave the azobenzenes 1jel in moderate yields, which was probably
caused by a steric repulsion. Also, a cyano group, which directly
bonded to a benzene ring, was sensitive to this reducing system,
leading to a decrease in the yield. However, when using the sub-
strate with a cyano group, which sandwiched a methylene chain,
the corresponding azobenzene 1n was obtained in a relatively good
yield. It is worth noting that the nitrobenzenes with either an acetyl
Scheme 2. Diverse approaches to azobenzenes.
We have reported that a reducing system comprised of an in-
dium (III) compound and a hydrosilane was highly effective for the
reduction of reducible agents, such as an aldehyde, a ketone, an
acetal, and a carboxylic acid.19,20 However, the conversion from
a nitrobenzene to an azobenzene in our previous work was limited
to several substituents.21 Herein, we report the full details of the
catalytic and reductive preparation of azobenzenes from a variety
of nitrobenzenes via the In(OTf)3eEt3SiH reducing system. We also
detail how this system was applied in the preparation of asym-
metrical azobenzene derivatives and in an intramolecular manner.
2. Results/discussion
Based on our previous study,21 when we initially examined the
reduction of nitrobenzene with InBr3 and Et3SiH under CHCl3 reflux
conditions, most of the nitrobenzene was recovered, and four types
of reductive products involving azobenzene (1a), azoxybenzene
(2a), hydrazobenzene (3a), and aniline (4a) were formed with low
selectivity (entry 1 in Table 1). Thus, to improve the product se-
lectivity, the effect from relatively high polar solvents, such as THF,
MeOH, and DMF, was investigated. As a result, THF and MeOH se-
lectively gave azoxybenzene (2a) and hydrazobenzene (3a), re-
spectively (entries 2 and 3). Also, when DMF was used, the
corresponding hydrazobenzene was obtained in an almost quan-
titative yield (entry 4). Then, when the effect of a counterion on the
indium compound in DMF was tested, neither InCl3 nor In(OAc)3
improved either the reactivity or the selectivity, but InCl3 gave
a small amount of azobenzene (entries 5 and 6). It is noteworthy
that when the equivalent of Et3SiH was reduced to 3 equiv in the
presence of InBr3 in DMF, the yield of azobenzene (1a) was in-
creased to a 59% yield (entry 7). This was probably due to con-
trolling the over-reduction of the azobenzene. Moreover, In(OTf)3

N. Sakai et al. / Tetrahedron 70 (2014) 2027e2033
2029
Table 2
,b
One-pot synthesis of a variety of azobenzene derivatives from monosubstituted nitrobenzenesa
a
Reaction conditions: nitrobenzene (1 mmol), catalyst (0.05 mmol), silane (3 mmol) in DMF (1 mL) at 60 ꢀC.
Time denotes the reaction time in the first step.
b
group or an ester group, which are sensitive to a common reducing
ratio of a nitrobenzene and p-nitroacetophenone was attempted.
For example, when the reaction was carried out using 3 equiv of
nitrobenzene and p-nitroacetophenone under conditions that
consisted of 0.1 equiv of In(OTf)3 and an excess amount (12 equiv) of
Et3SiH, after the usual column separation, the expected un-
symmetrical azobenzene 1t could be isolated in a 47% yield from
two homo-coupling azobenzenes. In a similar manner, the use of
nitrobenzene having either an electron-donating or -withdrawing
group also produced the corresponding unsymmetrical azo-
benzenes 1uew in moderate yields. The cross-coupling of p-chlor-
onitrobenzene with nitrobenzene (3 equiv) also gave the desired
unsymmetrical azobenzene derivative 1x in a practical yield.
Then, we applied the present method to an intramolecular ring-
closing reaction of 2,20-dinitrobiphenyl. As shown in Scheme 4, the
dinitro compound was treated with 5 mol % of In(OTf)3 and 3 equiv
of Et3SiH in DMF at 60 ꢀC for 4 h to isolate the intramolecular
coupling product, benzo[c]cinnoline (1y) in an excellent yield. Be-
cause aromatization of the formed hydrazine ring worked as
a driving force, this procedure needed no oxidative conversion
process from the formed hydrazine derivative to the corresponding
cyclic azobenzene under an ambient atmosphere.
reagent, were successfully converted to the azobenzene derivatives
1o and p in good yields. When the reaction was carried out using the
substrate with a sulfonamide group, the nitrobenzene was com-
pletely consumed, and the corresponding azobenzene 1q was ob-
tained. As an extension, when a similar reaction was performed
using disubstituted nitrobenzene derivatives including both a fluoro
group and a methyl group, the expected azobenzene derivatives 1r
and s were obtained in good yields (Scheme 3).
This reaction system was then applied to the one-pot prepara-
tion of unsymmetrical azobenzene derivatives (Table 3). From the
results shown in Scheme 1, an acetyl group showed a tolerance to
this reducing system, so that the control of selectivity using a molar
We anticipated the possibility that nitrosobenzene would be
one of the intermediates in the conversion series, and then per-
formed several control experiments (Scheme 5). When nitro-
sobenzene was directly conducted with 2 equiv of Et3SiH under our
standard conditions, as expected, the corresponding azobenzene
was selectively obtained in a 71% yield. Also, when a similar re-
action was carried out in the absence of In(OTf)3, the formation of
only azoxybenzene 2a, which was reductively prepared from the
Scheme 3. One-pot synthesis of azobenzene derivatives from disubstituted
nitrobenzenes.

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N. Sakai et al. / Tetrahedron 70 (2014) 2027e2033
Table 3
dimerization of nitrosobenzene, was observed in a 43% GC yield
One-pot synthesis of unsymmetrical azobenzene derivativesaec
with the recovery (50% GC yield) of the starting nitrosobenzene.
Moreover, running with only In(OTf)3 led to a drastic decrease
in the yield of the azoxybenzene 2a with the recovery (80% GC
yield) of nitrosobenzene. Consequently, these results show that
nitrosobenzene occupies one of the key intermediates of the re-
duction series and implies that the indium catalyst strongly acti-
vated the starting nitro group rather than the formed nitroso group,
and did not produce an indium hydride that may be derived from
an indium catalyst and a hydrosilane when using this system.
Moreover, the crossed reaction of nitrobenzene with p-chloroani-
line yielded only azobenzene 1a in an 80% yield and produced
neither the crossed azobenzene derivative nor the homo-coupling
azobenzene derived from p-chloroaniline (Scheme 6). Thus, these
results strongly support the theory that it is the generation of
a nitrosobenzene derivative rather than an aniline, that is, essential
for the reductive coupling of nitrobenzene derivatives.
Scheme 6. Examination of the cross-coupling from nitrobenzene and p-chloroaniline.
a
Reaction conditions: nitrobenzene (1 mmol), catalyst (0.1 mmol), silane
(12 mmol) in DMF (1 mL) at 60 ꢀC, under an air atmosphere in the second oxidation
step. Time denotes the reaction time in the second step.
Based on the control experiments, to arrive at a plausible
mechanism for the present coupling reaction, we assumed that the
conversion proceeds through the following path as shown in
Scheme 7. A hydrosilane initially reduces the nitrobenzene A, that
is, activated by the indium catalyst to produce nitrosobenzene B.
Then, the activated nitrosobenzene C undertakes dimerization to
form an azobenzene dioxide D, which is known to principally exist
as a monomer in solution,24 and a subsequent second reduction to
produce azoxybenzene E. Reduction of the azoxybenzene occurs,
finally leading to the formation of both the corresponding azo-
benzene F and the further reduced hydrazobenzene G. The hydra-
b
Reaction conditions: nitrobenzene (1 mmol), catalyst (0.1 mmol), silane
(12 mmol) in DMF (1 mL) at 60 ꢀC, under an O2 atmosphere in the second oxidation
step.
c
Reaction conditions: nitrobenzene (1 mmol), catalyst (0.1 mmol), silane
(10 mmol) in DMF (1 mL) at 60 ꢀC, under an O2 atmosphere in the second oxidation
step.
zobenzene G was converted back to azobenzene
F through
a subsequent oxidation reaction. Also, we anticipated that aniline H
would be formed via double reduction of nitrosobenzene C, rather
than being produced through the reductive cleavage of hydrazo-
benzene G.
Scheme 4. Intramolecular reductive ring-closing reaction of the dinitro compound.
Scheme 5. Conversion from nitrosobenzene to azobenzene 1a.
Scheme 7. Plausible reaction path from nitrobenzenes to azobenzenes.

N. Sakai et al. / Tetrahedron 70 (2014) 2027e2033
2031
3. Conclusions
(m, 2H), 7.39e7.42 (m, 2H), 7.72 (m, 4H); 13C NMR (125 MHz, CDCl3)
21.4, 120.4, 122.9, 128.9, 131.7, 139.0, 152.8; MS (EI): m/z 210 (Mþ,
d
In conclusion, we demonstrated that a reduction step com-
posed of In(OTf)3 and Et3SiH with a subsequent oxidation step
enabled a highly selective and a catalytic conversion of aromatic
nitro compounds into azobenzenes. We also found that the
reducing system enabled the direct one-pot preparation of un-
symmetrical azobenzenes. Moreover, we disclosed that this simple
catalytic system appears to be remarkably tolerant of a variety of
functional groups. The present method using In(OTf)3 and Et3SiH
provided a simpler and more convenient alternative to traditional
methods.
100%).
4.2.4. 4,40-Dimethylazobenzene13b (1d). 71% yield (89 mg); a pale
orange solid; mp 145.0e146.0 ꢀC; IR (KBr):
n
¼3416, 2911, 1598,
1485, 1141, 823, 702 cmꢂ1; 1H NMR (500 MHz, CDCl3)
d
2.43 (s, 6H),
7.30 (d, J¼8.0 Hz, 4H), 7.81 (d, J¼8.0 Hz, 4H); 13C NMR
(125 MHz, CDCl3)
(Mþ, 100%).
d 21.5, 122.7, 129.7, 141.2, 150.8; MS (EI): m/z 210
4.2.5. 4,40-Dimethoxyazobenzene14 (1e). 10
a brown solid; mp 149.8e151.6 ꢀC; IR (KBr):
%
n
yield (15 mg);
¼3092, 2843, 1588,
1573, 1499, 1241, 841 cmꢂ1 1H NMR (500 MHz, CDCl3)
; d 3.89 (s,
4. Experimental section
4.1. General
6H), 7.00 (d, 4H, J¼9.0 Hz), 7.88 (d, 4H, 9.0 Hz); 13C NMR (75 MHz,
CDCl3)
d
55.6, 114.2, 124.3, 147.1, 161.6; MS (FAB): m/z 242 (Mþ).
All manipulations were carried out under N2 atmosphere, unless
otherwise noted. Dimethylformamide (DMF) was distilled over
CaH2. All indium salts, metal catalysts, and nitrobenzenes were
commercially available and were used without further purification.
Triethylsilane or other hydrosilanes were used without further
purification. Reactions were monitored by TLC analysis of the re-
action aliquots. Thin-layer chromatography (TLC) was effected on
silica gel 60 F254, and components were located by observation
under UV light. Column chromatography was performed using
silica gel. 1H NMR spectra were measured at 500 (or 300)
MHz using tetramethylsilane as an internal standard. 13C NMR
spectra were measured at 125 (or 75) MHz using the center peak of
chloroform (77.0 ppm) as an internal standard. High resolution
mass spectra were measured using NBA (3-nitrobenzylalcohol) as
a matrix.
4.2.6. 4,40-Bis(dimethylamino)azobenzene17a
(72 mg); an orange powder; mp 256.7e258.3 ꢀC; IR (KBr):
(1f). 45%
yield
¼2928,
n
2784, 1601, 1511, 1367, 1148, 809 cmꢂ1 1H NMR (300 MHz,
;
CDCl3)
(75 MHz, CDCl3)
268 (Mþ).
d
6.76 (d, J¼9.0 Hz, 4H), 7.81 (d, J¼9.0 Hz, 4H); 13C NMR
d 40.4, 111.7, 124.0, 144.0, 151.5; MS (FAB): m/z
4.2.7. 4,40-Dichloroazobenzene14 (1g). 81% yield (121 mg); an or-
ange needles; mp 184.5e185.5 ꢀC; IR (KBr):
¼3449, 1568, 1475,
n
1080,1000, 843 cmꢂ1; 1H NMR (500 MHz, CDCl3)
d
7.49 (d, J¼8.5 Hz,
4H), 7.86 (d, J¼8.5 Hz, 4H); 13C NMR (125 MHz, CDCl3)
d 124.2,
129.4, 137.2, 150.8; MS (ESI): m/z 250 (Mþ, 100%), 252 (Mþþ2).
4.2.8. 4,40-Dibromoazobenzene14 (1h). 64% yield (130 mg); an or-
ange powder; mp 203.0e204.5 ꢀC; IR (KBr):
n
¼3452, 1571, 1475,
1394, 1067, 835 cmꢂ1; 1H NMR (500 MHz, CDCl3)
d
7.65 (d, J¼9.0 Hz,
4.2. General procedure for indium-catalyzed reductive syn-
thesis of azobenzene compounds
4H), 7.79 (d, J¼9.0 Hz, 4H); 13C NMR (125 MHz, CDCl3)
d 124.4,
125.8, 132.4, 151.2; MS (ESI): m/z 338 (Mþ, 51%), 340 (Mþþ2, 100%),
342 (Mþþ4, 49%).
To a 5 mL screw vial under N2 containing a freshly distilled DMF
(0.6 mL) were successively added aromatic nitro compound
(0.60 mmol), In(OTf)3 (0.030 mmol, 17 mg), and Et3SiH (1.80 mmol,
4.2.9. 4,40-Di(trifluoromethyl)azobenzene13b
(114 mg); an red solid; mp 97.3e99.1 ꢀC; IR (KBr):
(1i). 60%
yield
n
¼2924, 1611,
287
m
L). The resulting mixture was stirred at 60 ꢀC (bath temper-
1412, 1320, 1160, 1100, 849 cmꢂ1; 1H NMR (500 MHz, CDCl3)
d 7.80
ature), and monitored by TLC analysis. After completion of the re-
action, the resultant mixture was further stirred under either an
ambient or an O2 atmosphere during the corresponding reaction
time. The reaction was quenched with H2O (6 mL). The aqueous
layer was extracted with AcOEt (6 mLꢁ3), the combined organic
phases were dried over anhydrous Na2SO4, filtered, and evaporated
under reduced pressure. The crude product was purified by re-
crystallization from the solvent (hexane/chloroform) or silica gel
column chromatography (hexane/AcOEt) to afford the corre-
sponding azobenzene derivatives.
(d, J¼8.4 Hz, 4H), 8.03 (d, J¼8.4 Hz, 4H); 13C NMR (125 MHz, CDCl3)
d
123.3, 123.8 (q, JCeF¼272.4 Hz), 126.4 (q, JCeF¼3.7 Hz), 133.0 (q,
JCeF¼32.6 Hz), 154.1; MS (FAB): m/z 318 (Mþ, 100%).
4.2.10. 2,20-Difluoroazobenzene25 (1j). 51% yield (67 mg); an orange
solid; mp 99.6e101.0 ꢀC; IR (KBr):
n
¼1589, 1483, 1263, 1110,
856 cmꢂ1
;
1H NMR (500 MHz, CDCl3)
d
7.26 (m, 4H), 7.48 (m, 2H),
7.80 (m, 2H); 13C NMR (125 MHz, CDCl3)
d
117.1 (d, JCeF¼20.2 Hz),
117.9, 124.4 (d, JCeF¼3.8 Hz), 133.0 (d, JCeF¼8.2 Hz), 140.8
(d, JCeF¼3.8 Hz), 160.4 (d, JCeF¼258.6 Hz); MS (FAB) m/z 218 (Mþ).
4.2.1. Azobenzene13b (1a). 81% yield (88 mg); an orange solid; mp
4.2.11. 2,20-Dichloroazobenzene8b (1k). 50% yield (65 mg); an or-
65.0e66.0 ꢀC; IR (KBr):
n
¼3062, 1580, 1482, 1452, 1070, 775,
1H NMR (500 MHz, CDCl3)
7.46e7.54 (m, 3H),
122.8, 129.1, 131.0,
ange solid; mp 137.4e138.7 ꢀC; IR (KBr):
n
¼3056, 1592, 1521, 1462,
1H NMR (500 MHz, CDCl3)
7.38
(m, 4H), 7.56 (m, 2H), 7.70 (m, 2H); 13C NMR (125 MHz, CDCl3)
118.1, 127.4, 130.7, 132.2, 135.8, 148.8; MS (FAB) m/z 218 (Mþ).
689 cmꢂ1
;
d
1241, 1084, 1057, 950, 762 cmꢂ1
;
d
7.92e7.93 (m, 2H); 13C NMR (125 MHz, CDCl3)
d
152.7; MS (FAB): m/z 183 (MþþH), 154 (MþꢂN2 100%).
d
4.2.2. 2,20-Dimethylazobenzene13b (1b). 60% yield (76 mg); a red
4.2.12. 2,20-Diiodoazobenzene8b (1l). 48% yield (63 mg); a red
needle; mp 155.8e156.6 ꢀC; IR (KBr):
¼1561, 1455, 1245, 1037,
solid; mp 53.0e54.0 ꢀC; IR (KBr):
n
¼3452, 2913,1471,1113,1047, 768,
n
717 cmꢂ1; 1H NMR (500 MHz, CDCl3)
d
2.74 (s, 6H), 7.25 (m, 2H), 7.33
1014, 766 cmꢂ1; 1H NMR (500 MHz, CDCl3)
d 7.19 (m, 2H), 7.46 (m,
(m, 4H), 7.61e7.64 (m, 2H); 13C NMR (125 MHz, CDCl3)
d
17.6, 115.8,
2H), 7.76 (m, 2H), 8.04 (m, 2H); 13C NMR (125 MHz, CDCl3)
d 103.2,
126.3, 130.7, 131.2, 138.0, 151.1; MS (EI): m/z 210 (Mþ, 100%).
118.3, 129.0, 132.8, 139.9, 150.9; MS (FAB) m/z 218 (Mþ).
4.2.3. 3,30-Dimethylazobenzene13b (1c). 70% yield (88 mg); a dark
4.2.13. 4,40-Dicyanoazobenzene14 (1m). 23% yield (32 mg); a red
solid; mp 234.6e235.2 ꢀC; IR (KBr):
¼2921, 2223, 1485, 1404, 1298,
1098, 1012, 854, 836 cmꢂ1 1H NMR (500 MHz, CDCl3)
7.86 (d,
orange solid; mp 50.3e51.6 ꢀC; IR (KBr):
n
¼2920, 1604, 1467, 1251,
n
794, 698 cmꢂ1; 1H NMR (500 MHz, CDCl3)
d
2.46 (s, 6H), 7.28e7.29
;
d

2032
N. Sakai et al. / Tetrahedron 70 (2014) 2027e2033
J¼8.0 Hz, 4H), 8.04 (d, J¼8.0 Hz, 4H); 13C NMR (125 MHz, CDCl3)
122.9, 126.5, 129.4, 131.4, 131.8, 138.1, 139.0, 150.6, 155.3, 197.5; MS
(FAB): m/z 239 (MþþH, 15%), 73 (100%); HRMS (FAB-Magnetic
Sector): Calcd for C15H14N2O: 238.1106, Found: 238.1081.
d
115.2, 118.1, 123.7, 133.4, 154.0; MS (EI): m/z 232 (Mþ, 100%).
4.2.14. 4,40-Di(cyanomethyl)azobenzene17a
(100 mg); a yellow solid; mp 195.5e197.0 ꢀC; IR (KBr):
(1n). 64%
yield
n
¼2916,
4.2.22. 4-Acethyl-40-methylazobenzene14 (1v). 44% yield (63 mg);
2242, 1610, 1429, 1109, 821 cmꢂ1; 1H NMR (500 MHz, CDCl3)
d
3.86
a red solid; mp 106.1e109.5 ꢀC; IR (KBr):
n
¼1673, 1597, 1356, 1265,
(s, 4H), 7.50 (d, J¼8.5 Hz, 4H), 7.94 (d, J¼8.5 Hz, 4H); 13C NMR
1001, 969, 854, 826, 702 cmꢂ1; 1H NMR (300 MHz, CDCl3)
d
2.45 (s,
(125 MHz, CDCl3)
d
23.6, 117.3, 123.7, 128.8, 132.9, 152.1; MS (FAB):
3H), 2.67 (s, 3H), 7.34 (d, 2H, J¼8.4 Hz), 7.87 (d, 2H, J¼8.1 Hz), 7.95
m/z 261 (MþþH, 7%), 154 (100%).
(d, 2H, J¼8.7 Hz), 8.10 (d, 2H, J¼8.7 Hz); 13C NMR (75 MHz, CDCl3)
d
21.6, 26.9,122.8,123.2,129.4,129.9,138.1,142.6,150.7,155.2,197.5;
4.2.15. 4,40-Diacethylazobenzene14 (1o). 88% yield (140 mg); a pale
MS (FAB): m/z 238 (Mþ, 10%), 83 (100%).
red powder; mp 208.5e209.8 ꢀC; IR (KBr):
n
¼1674, 1466, 1252,
1229, 1102, 963, 835 cmꢂ1; 1H NMR (500 MHz, CDCl3)
d
2.68 (s, 6H),
4.2.23. 4-Acetyl-20-fluorolazobenzene (1w). 54% yield (78 mg);
8.01 (d, J¼8.0 Hz, 4H), 8.13 (d, J¼8.0 Hz, 4H); 13C NMR (125 MHz,
a red solid; mp 112.6e114.6 ꢀC; IR (KBr):
n
¼3335, 3014, 1675, 1591,
CDCl3)
d
26.8, 123.2, 129.4, 138.9, 154.8, 197.3; MS (FAB): m/z 267
1480, 1351, 1219, 959, 850, 771 cmꢂ1 1H NMR (300 MHz, CDCl3)
;
(MþþH), 73 (100%).
d
2.67 (s, 3H), 7.27 (m, 2H), 7.51 (m, 1H), 7.79 (dd, 1H, J¼7.8, 7.8 Hz),
8.00 (d, 2H, J¼8.7 Hz), 8.11 (d, 2H, J¼8.4 Hz); 13C NMR (75 MHz,
4.2.16. Dimethylazobenzene-4,40-dicarboxylate21 (1p). 85% yield
CDCl3)
d
26.9, 117.2 (d, JCeF¼19.9 Hz), 117.6, 123.2, 124.4
(152 mg); an orange powder; mp 223.1e224.4 ꢀC; IR (KBr):
n
¼2916,
(d, JCeF¼4.0 Hz), 129.4, 133.4 (d, JCeF¼8.7 Hz), 138.7, 140.6
(d, JCeF¼6.9 Hz), 155.1, 160.5 (d, JCeF¼259.0 Hz), 197.4; MS (FAB): m/
z 243 (MþþH, 33%), 73 (100%). HRMS (FAB-Magnetic Sector): Calcd
for C14H11FN2O: 242.0855, Found: 242.0876.
1734, 1478, 1292, 1116, 873, 775 cmꢂ1 1H NMR (500 MHz, CDCl3)
;
d
3.97 (s, 6H), 7.99 (d, J¼8.0 Hz, 4H), 8.21 (d, J¼8.0 Hz, 4H); 13C NMR
(125 MHz, CDCl3)
z 298 (Mþ, 100%).
d 52.4,122.9, 130.7, 132.4,154.9,166.4; MS (EI): m/
4.2.24. 4-Chloroazobenzene21 (1x). 62% yield (79.1 mg); an orange
4.2.17. 4,40-Azobenzenedisulfonamide26 (1q). This compound could
be isolated by a silica gel column chromatography (eluent: THF);
53% yield (108 mg); a beige powder; decomposed 385 ꢀC, IR (KBr):
solid; IR (KBr):
n
¼2966, 2925, 1636, 1381, 1268, 1085, 1025,
7.45e7.54 (m, 5H),
122.9, 124.1, 129.1,
802 cmꢂ1 1H NMR (300 MHz, CDCl3)
;
d
7.85e7.92 (m 4H); 13C NMR (75 MHz, CDCl3)
d
n
¼3587, 3363, 3272, 3080, 1604, 1546, 1346, 1162, 856, 702 cmꢂ1
;
129.3, 131.3, 136.9, 150.9, 152.4; MS (FAB): m/z 216 (Mþ, 100%).
1H NMR; (300 MHz, DMSO-d6) 7.60 (s, 2H), 8.03e8.11 (m, 4H); 13
d C
NMR; (75 MHz, DMSO-d6) d 124.0, 127.2, 146.6, 153.2; MS (ESI): m/z
4.2.25. Benzo[c]cinnoline18b (1y). 95% yield (102 mg); a pale yellow
340 (Mþ, 100%); HRMS (ESI-TOF): Calcd for C12H11N4O4S2:
339.0222, Found: 339.0214.
crystal; mp 155.5e156.1 ꢀC; IR (KBr):
1082, 759 cmꢂ1 1H NMR (300 MHz, CDCl3)
n
¼3056, 1611, 1431, 1353, 1117,
7.90e7.94 (m, 4H),
;
d
8.57e8.60 (m, 2H), 8.74e8.77 (m, 2H); 13C NMR (125 MHz, CDCl3)
4.2.18. Bis(4-fluoro-3-methylphenyl)diazene27
(93 mg); a yellow needle; mp 163.1e164.5 ꢀC; IR (KBr):
1579, 1487, 1409, 1248, 1195, 1097, 903, 822 cmꢂ1
(1r). 63%
yield
¼2935,
d
120.9, 121.4, 129.2, 131.3, 131.5, 145.3; MS (FAB): m/z 181 (MþþH).
n
;
1H NMR
Acknowledgements
(300 MHz, CDCl3)
d
2.36 (s, 6H), 7.33 (dd, 2H, J¼7.5, 7.5 Hz), 7.56 (d,
2H, J¼8.7 Hz), 7.66 (d, 2H, J¼8.1 Hz); 13C NMR (75 MHz, CDCl3)
This work was partially supported by a Grant-in-Aid for Scien-
tific Research (C) (No. 25410120) from MEXT (Japan). The authors
thank Shin-Etsu Chemical Co., Ltd., for the gift of the hydrosilanes.
d
14.7 (d, JCeF¼3.2 Hz), 115.6 (d, JCeF¼23.9 Hz), 122.6 (d,
JCeF¼8.9 Hz), 125.4 (d, JCeF¼6.3 Hz), 125.8 (d, JCeF¼19.0 Hz), 148.8
(d, JCeF¼2.3 Hz), 162.9 (d, JCeF¼250.7 Hz); MS (EI): m/z 246 (Mþ,
5%), 68 (100%); HRMS (FAB-Magnetic Sector): Calcd for C14H12F2N2:
246.0969, Found: 246.0994.
Supplementary data
4.2.19. Bis(4-methyl-3-fluorophenyl)diazene27
(118 mg); an orange needle; mp 97.8e100 ꢀC; IR (KBr):
1409, 1253, 1185, 1096, 949, 874 cmꢂ1
(1s). 80%
yield
1H and 13C NMR spectra of the azobenzenes prepared using this
method. Supplementary data related to this article can be found at
http://dx.doi.org/10.1016/j.tet.2014.01.048.
n
¼1579,1493,
;
1H NMR (500 MHz, CDCl3)
d
2.37 (s, 6H), 7.13 (m, 2H), 7.75 (m, 4H); 13C NMR (75 MHz, CDCl3)
d
14.8 (d, JCeF¼3.2 Hz),107.5 (d, JCeF¼23.9 Hz),120.5 (d, JCeF¼3.2 Hz),
References and notes
128.4 (d, JCeF¼18.2 Hz), 131.6 (d, JCeF¼5.5 Hz), 152.1, 161.6 (d,
JCeF¼246.6 Hz); MS (EI): m/z 246 (Mþ, 45%),109 (100%); HRMS (FAB-
Magnetic Sector): Calcd for C14H12F2N2: 246.0969, Found: 246.0992.
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