Oxidative dimerization of (hetero)aromatic amines utilizing t-BuOI leading to (hetero)aromatic azo compounds: Scope and mechanistic studies

Article abstract of DOI:10.1021/jo402120w

A straightforward synthetic method of both symmetric and unsymmetric aromatic azo compounds through an efficient and cross-selective oxidative dimerization of aromatic amines using tert-butyl hypoiodite (t-BuOI) under metal-free and mild conditions has been developed. This method was also found applicable to the synthesis of heteroaromatic azo compounds. The spectroscopic study indicates the involvement of N,N-diiodoanilines in the oxidative reaction as the key intermediate.

Full text of DOI:10.1021/jo402120w

Article
pubs.acs.org/joc
Oxidative Dimerization of (Hetero)aromatic Amines Utilizing t‑BuOI
Leading to (Hetero)aromatic Azo Compounds: Scope and
Mechanistic Studies
Sota Okumura,† Chun-Hsuan Lin,† Youhei Takeda,*,†,‡ and Satoshi Minakata*,†
‡
†Department of Applied Chemistry and Frontier Research Base for Global Young Researchers, Graduate School of Engineering,
Osaka University, Yamadaoka 2-1, Suita, Osaka 565-0871, Japan
S
* Supporting Information
ABSTRACT: A straightforward synthetic method of both symmetric and un-
symmetric aromatic azo compounds through an efficient and cross-selective
oxidative dimerization of aromatic amines using tert-butyl hypoiodite (t-BuOI)
under metal-free and mild conditions has been developed. This method was
also found applicable to the synthesis of heteroaromatic azo compounds. The
spectroscopic study indicates the involvement of N,N-diiodoanilines in the
oxidative reaction as the key intermediate.
organic compounds. More specifically, the main problem
of these approaches lies in the substrate scope, which is limited
to the combination of electron-rich and -deficient aromatic
amines, because of their reaction mechanisms. To address these
issues, recently, catalytic approaches using oxygen as an oxidant
INTRODUCTION
■
For over a century, azobenzene derivatives have been utilized
as organic dyes in industry.1 In addition to such traditional use
of azobenzenes, over the past few decades, there has been a
rapid growth in interest in their next-generation applications as
photoresponsive soft materials such as smart polymers,2 liquid
crystals,3 photochromic ligands for optochemical genetics,4 and
photoswitches in biological systems,5 owing to their intrinsic
ability of photochemical cis/trans-isomerization.6 In terms of
their preparation, a myriad of synthetic methods are available
nowadays.7 However, an appropriate choice of synthetic
method would mostly depend on the structural symmetry of
azobenzenes of interest (i.e., symmetric or unsymmetric types).
As for the preparation of symmetric azobenzenes, direct syn-
thetic methods starting from readily available organic com-
pounds involve reductive homodimerization of nitrobenzenes8
and oxidative homodimerization of aromatic amines.9 None-
theless, the former often confronts the difficulty in controlling
product distribution of the azo-/azoxybenzene ratio, and the
latter suffers from the stoichiometric use of environmentally
unfriendly heavy-metal oxidants such as BaMnO4, Pb(OAc)4,
AgO, and HgO. Although Cu-catalyzed homodimerization pro-
cesses of aromatic amines using air as the co-oxidant have been
developed to avoid the use of heavy-metal salts,10 incompat-
ibility of functional groups and low yields of desired products
are still inevitable. On the other hand, unsymmetric aromatic
azo compounds have been exclusively synthesized by diazo-
nium coupling11 and the Mills reaction.12 These reactions
require the preparation of explosive diazonium salts or toxic
nitrosobenzenes as substrates from commercially available
have been developed.13 While Grirrane, Corma, and Garcia
́
realized the air-oxidation system by employing Au/TiO2 nano-
particles,13a,b He and Li utilized Ag nanoparticles as a hetero-
geneous catalyst.13c The Jiao’s group reported Cu/pyridine-catalyzed
aerobic oxidative dimerization of aniline derivatives.13d Furthermore,
an organocatalytic approach using hypervalent iodine(III) has
also been developed by Ma and Lei.14 Although these reports
succeeded in synthesizing a series of unsymmetric azobenzenes,
there still remains considerable room for improvement in each
method: the harsh conditions employing high pressurized O2
(5 bar) and a high temperature (100 °C) in the Au/TiO2
system, the stoichiometric use of a strong base (KOH) in the
Ag-nanoparticle system, and the use of excess amounts of the
electron-deficient aromatic amines in the Cu/pyridine system.
Therefore, the development of robust synthetic methods of
azobenzene derivatives with high efficiency, wide diversity, and
high functional compatibility is significantly desirable.
In this regard, we have recently reported an efficient, lower-
energy-consuming, and metal-free synthetic method for both
symmetric and unsymmetric aromatic azo compounds through
oxidative dimerization of aromatic amines (Scheme 1),15 utilizing
a unique monovalent iodine-containing reagent, tert-butyl
Received: September 25, 2013
© XXXX American Chemical Society
A
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a
Scheme 1. Oxidative Dimerization of Aromatic Amines
Table 1. Effect of Halogen-Containing Oxidants
Using t-BuOI
hypoiodite (t-BuOI).16 The key concept of the oxidative
reaction involves the umpolung reactivity of aromatic amines,
converting ArNH2 as a nucleophile into ArNI2 as an elec-
trophile through an efficient H/I exchange process mediated by
t-BuOI (Scheme 1).17 Our preliminary study revealed that the
reaction conditions were applicable to a wide range of anilines
with high functional compatibility under mild reaction
conditions. The successful results prompted us to further
expand the substrate scope to heteroaromatic amines: hetero-
aromatic azo compounds can find new applications such as
nonliner optical (NLO) materials18 and photodissociable
ligands (PDLs).19 We also became interested in the application
of our method to the practical preparation of functional
materials. Furthermore, we continued to pursue mechanistic
details of the oxidative reaction. Herein, we disclose the
detailed course of reaction development, the full scope of
substrates, and the synthetic applications to efficient prepara-
tion of photochemical switches. Furthermore, mechanistic
aspects probed by NMR and MS spectroscopy are discussed.
RESULTS AND DISCUSSION
■
Development of Oxidative Homodimerization of
(Hetero)aromatic Amines. The reagent t-BuOI was readily
generated in situ from commercially available and inexpensive
reagents, tert-butyl hypochlorite (t-BuOCl) and sodium iodide
(NaI).17 Initially, we examined an oxidative homodimerization
of aniline (1a) as the model reaction. When 1a (0.5 mmol) was
treated with 2 equiv of t-BuOI (1 mmol) in acetonitrile at room
temperature for 1 h, oxidative homodimerization forming a
NN double bond was found to smoothly proceed to give
trans-azobenzene 2aa in 95% yield (Scheme 2).
Scheme 2. Homodimerization of Aniline (1a)
a
Reaction conditions: 1b (0.5 mmol) and halogen-containing oxidant
b
(1 mmol) in Et2O (3 mL) at room temperature for 1 h. 1H NMR
yields. Isolated yield. 0.5 mmol of DIH was used.
c
d
reagents also turned out to be a quite important factor: when
t-BuOCl was first added prior to NaI, no dimerized product was
produced and only monochlorinated amine was detected. This
result suggests that in situ generation of t-BuOI is much faster
than the chlorination of the amine by t-BuOCl.
Having confirmed the superiority of t-BuOI, the substrate
scope of the oxidative homodimerization was investigated
(Table 2). Anilines bearing an electron-donating substituent
such as methyl-, methoxy-, and N,N-dimethylamino groups at
the para position were readily transformed into the cor-
responding aromatic azo compounds 2bb−2dd in moderate to
high yields (entries 2−4). Halo-substituted anilines were applicable
to the reaction conditions to give the corresponding products
in high yields (entries 5−8). Although the homodimerization of
electron-deficient aromatic amines required prolonged times
compared to the reactions of electron-rich amines, the cor-
responding azo compounds were produced in excellent yields
To confirm the superiority of the system, we examined other
electrophilic halogen-containing oxidants in the homodimeriza-
tion of p-toluidine (1b) (Table 1). Whereas the use of t-BuOI
afforded azo product 2bb in 97% yield (entry 1), t-BuOCl was
found to be ineffective for the reaction (entry 2). Iodinating
reagents composed of diatomic interhalogen molecules (I2, ICl,
IBr) and the combination of I2/Et3N failed to give the prod-
uct (entries 3−6). Widely used halogenating reagents,
N-chlorosuccinimide (NCS), N-bromosuccinimide (NBS), and
N-iodosuccimide (NIS) also did not give satisfactory yields of
2bb in any of the cases (entries 7−9). The employment of
N-iodopyrrolidin-2-one, 1,3-diiodo-5,5-dimethylhydantoin (DIH),
N-iodophthalimide (NIPI), and N-iodosaccharin (NISac) resulted
in rather low yields of 2bb (entries 10−13). The use of a highly
electrophilic iodonium reagent, IPy2BF4 (BPIT), failed to provide
the desired product (entry 14). The order of the addition of
B
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a
Table 2. Homodimerization of Aromatic Amines
b
entry
1
Ar
conditions
2
yield [%]
1
1a
1b
1c
1d
1e
1f
Ph
MeCN, rt, 1 h
Et2O, rt, 1 h
2aa
2bb
2cc
2dd
2ee
2ff
95
97
87
69
95
96
83
88
95
91
89
79
67
86
78
44
73
89
94
67
2
p-Me-C6H4
p-MeO-C6H4
p-Me2N-C6H4
p-F-C6H4
3
MeCN, rt, 0.25 h
DMF, 0 °C, 6 h
acetone, rt, 6 h
Et2O, −20 °C, 12 h
acetone, rt, 3 h
Et2O, −20 °C, 12 h
Et2O, rt, 3 h
4
5
6
p-Cl-C6H4
7
1g
1h
1i
p-Br-C6H4
2gg
2hh
2ii
8
p-I-C6H4
9
p-EtO2C-C6H4
p-Me(O)C-C6H4
p-NC-C6H4
p-O2N-C6H4
10
11
1j
Et2O, −20 °C, 12 h
THF, rt, 12 h
2jj
1k
1l
2kk
2ll
c
12
THF, rt, 6 h
13
14
15
16
17
18
19
20
1m
1n
1o
1p
1q
1r
1s
1t
p-(Ph-NN)-C6H4
THF, −20 °C, 24 h
acetone, rt, 3 h
THF, −20 °C, 12 h
Et2O, −20 °C, 36 h
Et2O, rt, 24 h
2 mm
2nn
2oo
2pp
2qq
2rr
m-Cl-C6H4
m-O2N-C6H4
o-Ph-C6H4
o-NC-C6H4
3,4-Me2C6H3
3,5-(F3C)2C6H3
F5C6
Et2O, rt, 1 h
THF, rt, 12 h
2ss
Et2O, rt, 12 h
2tt
a
b
c
Reaction conditions: 1 (0.5 mmol), t-BuOCl (1 mmol), and NaI (1 mmol) in solvent (3 mL). Isolated yields. 2 mmol of t-BuOCl and NaI were
used.
a
Table 3. Homodimerization of Heteroaromatic Amines
a
b
Reaction conditions: 1 (0.5 mmol), t-BuOCl (1 mmol), and NaI (1 mmol) in solvent (3 mL). Isolated yields.
C
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Table 4. Cross-dimerization of Aromatic Amines
D
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Table 4. continued
a
b
Reaction conditions: Ar1NH2 (0.25 mmol), Ar2NH2 (0.25 mmol), t-BuOCl (1 mmol), and NaI (1 mmol) in solvent (3 mL). Isolated yields.
c
d
1b (0.5 mmol), 1j (0.25 mmol), t-BuOCl (1.5 mmol), and NaI (1.5 mmol). 1i (0.25 mmol), 1l (0.5 mmol), t-BuOCl (1.5 mmol), and NaI
(1.5 mmol).
(entries 9−12). Notably, the employment of amino-azobenzene
1m under the oxidative conditions gave homodimerized prod-
uct 2 mm, which is regarded as an aza-analogue of oligo(p-
phenylenevinylene)s. meta-Substitution on the benzene ring
did not significantly affect the yields of the products (entries 14
and 15). Anilines having a substituent at the ortho position were
successfully transformed into the corresponding azobenzenes in
moderate yields, despite requiring extended reaction times (entries
16 and 17). It should be noted that the homodimerization of
multiply substituted aromatic amines gave the corresponding azo
products in high yields (entries 18−20).
Motivated by the successful results of the homodimerization
of aniline derivatives, we then extended substrate scope to
heteroaromatic amines (Table 3). To our delight, the reaction
conditions were applicable to five-membered heteroaromatic
amines such as pyrazine and oxazole, which are much more
electron-rich than aniline and labile toward oxidative con-
ditions, affording the corresponding products 2uu and 2vv in
good yields (entries 1 and 2). Benzene-fused heteroaromatic
amines also successfully dimerized to give homodimers (entries
3−5). Carbazole-containing amine 1z was also applicable to the
reaction (entry 6). In addition to the potential applications as
NLO materials and PDLs, these heteroaromatic compounds
can serve as an oxidant in the Mitsunobu reaction.20 In respect
to the limitation of the scope of heteroaromatic amines, electron-
poor heteroaromatic amines such as 2-methylquinolin-5-amine
and isoquinolin-5-amine did not give the homodimerized
products at all or resulted in rather low yields of the products
(e.g., in the case of 4-aminopyridine, the corresponding product
was formed in less than 50% 1H NMR yield and was difficult to
isolate).
Scope of Oxidative Cross-dimerization of (Hetero)-
aromatic Amines. The successful homodimerization of
aromatic amines into symmetric azo compounds prompted us
to apply the reaction conditions to cross-dimerization (Table 4).
Initially, we examined the cross-dimerization of p-toluidine (1b)
with an equimolar amount of ethyl 4-aminobenzoate (1i).
It was revealed that the corresponding unsymmetric azo com-
pound 2bi was dominantly produced in 62% yield over the
homodimers 2bb and 2ii (32% and 30% yields, respectively)
(entry 1). Considering the difficulty in achieving cross-
dimerization of aromatic amines in an oxidative way, this result
demonstrates the high superiority of our method.21 The cross-
dimerization of 1b with 1j and 1l also proceeded to give push−
pull-type aromatic azo compounds 2bj and 2bl in high yields in
both cases (entries 2 and 3). When p-toluidine (1b) was treated
with meta-substituted anilines 1n, 1o, and 1s, the correspond-
ing aromatic azo compounds 2bn, 2bo, and 2bs were obtained
in moderate to good yields (entries 4−6). Cross-dimerization
reactions of an electron-deficient aniline, 4-aminoacetophenone
(1j), with various aromatic amines were also examined (entries
7−13). Aniline (1a) selectively reacted with 1j, leading to the
monoacetylated azo compound 2aj in good yield (entry 7).
Anilines containing electron-withdrawing and halogen groups
were also applicable to the reaction conditions to afford the
corresponding unsymmetric azobenzenes in high yields (entries
8−13). Cross-dimerization of highly electron-deficient anilines
1i and 1l also proceeded to give unsymmetric azobenzene 2il in
a selective way, albeit requiring longer time (entry 14). Since it is
difficult to synthesize unsymmetric aromatic azo compounds bear-
ing two electron-deficient aromatic rings by conventional methods,
this result clearly highlights the advantage of our method.
E
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a
Table 5. Cross-dimerization of Heteroaromatic Amines with Aniline Derivatives
a
b
c
Reaction conditions: Ar1NH2 (0.25 mmol), Ar2NH2 (0.25 mmol), t-BuOCl (1 mmol), and NaI (1 mmol) in solvent (3 mL). Isolated yields. 1b
(0.5 mmol), 1v (0.25 mmol), t-BuOCl (1.5 mmol), and NaI (1.5 mmol).
The scope of the cross-dimerization of heteroaromatic
amines with aniline derivatives is shown in Table 5. Five-
membered heteroaromatic amine 1v smoothly reacted with 1b
to give the corresponding product 2bv in good yield (entry 1).
The reaction of 2-amino-1-methyl benzimidazole (1w) with
various anilines (1b, 1g, 1j, and 1s) proceeded to provide
unsymmetric azo products in moderate to high yields
(entries 2−5). This method was also applicable to the cross-
dimerization reactions of 1b with 2-aminobenzothiazole
(1x, entry 6) and 6-aminobezothiazole (1y, entry 7). In all
cases, unsymmetric azobenzenes were dominantly produced
over homodimers and easily separated by column chromatog-
raohy.
Synthetic Applications of the Oxidative Dimerization.
To demonstrate the practicality of the oxidative dimerization
method, a gram-scale synthesis of azo product was conducted
(Scheme 3). When 10 mmol of ethyl 4-aminobenzoate (1i) was
treated with a 20 mmol of t-BuOI in 60 mL of Et2O at room
temperature for 3 h, the homodimerized product 2ii was
successfully synthesized in 93% yield without any significant
F
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a
Scheme 3. Gram-Scale Synthesis of Azobenzene 2ii
Table 6. Effect of Base on the Homodimerization
b
entry
t-BuOI [mmol]
base
yield [%]
c
1
2
3
4
5
1
97
loss of reaction efficiency, compared with the small-scale run
(0.5 mmol).
0.5
0.5
0.5
0.5
16
18
50
53
2,6-lutidine
t-BuOK
Taking advantage of this straightforward and efficient
synthetic method, highly improved syntheses of azobenzene-
based photoswitches22 were demonstrated (Scheme 4).
d
(Me3Si)2NH
a
Reaction conditions: 1b (0.5 mmol), t-BuOCl (0.5−1 mmol), NaI
b
(0.5−1 mmol), and base (0.5 mmol) in Et2O (3 mL). 1H NMR
yields. Isolated yield. 0.25 mmol of hexamethyldisilazane was used.
Scheme 4. Efficient Syntheses of Photoswitches 4bb and 4cc
c
d
was examined, with the amount of t-BuOI being reduced by
half (Table 6). A blank experiment resulted in rather low yield
of product 2bb (entry 2). The addition of 2,6-lutidine did not
significantly affect the efficiency of the reaction (entry 3). In
contrast, the employment of stronger bases such as t-BuOK
(entry 4) and hexamethyldisilazane (entry 5) resulted in much
higher product yields, albeit much lower than with the standard
conditions (entry 1). These results suggest that t-BuOI serves
as the most appropriate trapping agent against HI in the actual
system.
Table 7 shows the results of the homodimerization of 1b
conducted under radical-inhibiting conditions. Clearly, radical
Table 7. Homodimerization under Radical-Inhibiting
a
Conditions
́
Recently, Bleger, Brouwer, and Hecht have developed a new
b
class of photoswitches 4bb and 4cc, which can undergo E/Z
isomerization under visible light irradiation of in a nearly
quantitative efficiency.22b When 4-bromo-2,6-difluoroaniline
(3a) was treated with 2 equiv of t-BuOI in t-BuOH at room
temperature for 3 h, tetrafluoroazobenzene 4aa was obtained in
62% yield (Scheme 4a). Additionally, this reaction was
applicable to a 5-fold scale operation, producing 4aa in 56%
yield. Two bromo functionalities of 4aa were then efficiently
substituted with two acetamide groups through Pd-catalyzed
amidation,22b leading to azobenzene 4bb. Homodimerization
of 3b also smoothly proceeded to give 4cc in a high yield
(Scheme 4b). According to the literature,22b the conventional
synthetic method for 4aa and 4cc required excess amounts of
heavy metal oxidants (KMnO4/FeSO4·7H2O), and 4aa and 4cc
were produced in rather low yields (22% and 23% yield,
respectively). Therefore, our oxidative method allows for much
more efficient access to these useful functional molecules.
Mechanistic Studies. For deeper understanding of the
reaction mechanism, several experiments were conducted. The
pH of the aqueous layer extracted from the reaction mixture of
homodimerization of p-toluidine (1b) indicated 4.75, suggest-
ing that hydrogen iodide (HI) was liberated during the reac-
tion.23 Hydrogen iodide could be trapped by t-BuOI to generate
t-BuOH and I2. If the generated acid (HI) is efficiently trapped
by an adventitious base, the stoichiometry of t-BuOI should be
reduced by half. To verify the assumption, the addition of bases
entry
additional conditions
yield [%]
c
1
2
3
4
5
97
c
addition of TEMPO
addition of Galvinoxyl
under O2 atmosphere
in the dark
94
c
88
89
92
a
Reaction conditions: 1b (0.5 mmol), t-BuOCl (1 mmol), NaI
(1 mmol), and additive (1 mmol, entries 2 and 3) in Et2O (3 mL).
b
c
1H NMR yields. Isolated yield.
scavengers (TEMPO and Garvinoxyl, entries 2 and 3), oxygen
(entry 4), and light shielding (entry 5) did not affect the
product yields, suggesting that it is not likely to involve the
radical species in the dimerization reaction.
On the basis of our preliminary assumption, we pursued the
possibility of the involvement of ArNI2 as the key intermediate.
The results of NMR monitoring of aromatic amines under
the effect of t-BuOI are summarized in Scheme 5, and repre-
sentative NMR spectra of the experiments are also provided
in Figures 1−3. When 2 equiv of t-BuOI were added to the d6-
DMSO solution of 1e, the signal corresponding to the two
N−H hydrogens (δ = 4.93 ppm) disappeared, and aromatic
hydrogens (δ = 6.51 and 6.82 ppm) shifted to the lower field
(δ = 6.65 and 6.87 ppm, respectively) (eq 1 in Scheme 5,
Figure 1a, and b). Similar phenomena were observed in the
G
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Scheme 5. Summary of NMR Monitoring of H/I Exchange of Aromatic Amines
1
Figure 1. H NMR spectra of 1e and 1j in d6-DMSO recorded at room temperature: (a, c) the mixture of aromatic amine (0.05 mmol) and NaI
(0.1 mmol); (b, d) the mixture after adding t-BuOCl (0.1 mmol).
H
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Figure 2. 13C NMR spectra of 1j in d6-DMSO recorded at room temperature: (a) the mixture of 1j (0.05 mmol) and NaI (0.1 mmol); (b) the
mixture after adding t-BuOCl (0.1 mmol).
Figure 3. 15N NMR spectra of 1a-15N in d6-DMSO recorded at room temperature: (a) the mixture of 1a-15N (0.1 mmol) and NaI (0.2 mmol); (b)
the mixture after adding t-BuOCl (0.2 mmol).
Scheme 6. Competitive Study of H/I Exchange
cases of 1j and 1b (eqs 2 and 3 in Scheme 5, Figure 1c, and d).
These results suggested that the double proton exchange process is
very rapid. Furthermore, 13C and 15N NMR analyses of the chemical
species generated as the result of the proton exchange were also
conducted (eqs 4 and 5 in Scheme 5, Figures 2 and 3). Notably,
upon treating separately 1j and 1a labeled with 15N (1a-15N) with
t-BuOI, the chemical shifts of the C1 of 1j and the N of 1a-15N
were moved to the upper regime by 0.94 and 1.00 ppm, respectively
(Figures 2 and 3), which implies the presence of some sort of “heavy
atoms” on the N atom.24 This was also partly supported by the ob-
servation of a singlet peak of 1a-15N under the nondecoupled con-
ditions.25 To further prove the generation of N,N-diiodoaniline,26
ESI-MS analysis of the reaction system was conducted using 3a as a
reactant. Although the molecular ion peak of N,N-diiodoaniline was
not detected, the mass fragment of C6H3BrF2NI, which corresponds
to a radical cation of N-monoiodinated 3a, was detected. This
radical cation species could generate through the homolytic cleavage
of the N−I bond of the corresponding ammonium form of N,N-
diiodoaniline (ArNI2H+),27,28 probably due to the rather small dis-
sociation energy of N−I bond (∼130 kJ/mol).29,30 Taken together,
N,N-diiodoanilines most likely to generate through an efficient H/I
exchange process.
To further gain insights into the H/I exchange process,
an equimolar mixture of 1e and 1j was treated with t-BuOI
(2 equiv). As the result, 1H NMR spectra indicated the exclusive
generation of p-fluoro-N,N-diiodoaniline from 1e with keeping
1j intact (eq 1 in Scheme 6 and Figure 4). Likewise, the similar
experiment using 1b and 1j also suggested the exclusive genera-
tion of N,N-diiodoaniline derived from 1b, while 1j remained
unreacted (Scheme 6, eq 2). Taking into account the Hammett
constants (σp) of F, Ac, and Me being 0.06, 0.50, and −0.17,31
respectively, the H/I exchange proceeded more predominantly
with the electron-richer aniline than with the electron-poorer
aniline, at least on the NMR time scale.
Based on these experimental results, a plausible reaction
mechanism is illustrated in Scheme 7. On the basis of the fact
that the electron-richer aniline was preferentially diiodinated,
we propose H/I exchange mechanism through “halogen bond-
ing”32 formation between the nitrogen and iodine atoms (A) to
generate intermediate B. Based on this concept, the exchange
process of a strong Lewis base (an electron-richer amine)
would be more favorable than that with a weak base (an
electron-poorer amine), which is in good agreement with the
results of NMR experiments. The resulting ammonium salt B
I
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Figure 4. 1H NMR spectra of the mixture of 1e (indicated in green) and 1j (indicated in violet) in d6-DMSO recorded at room temperature: (a) the
mixture of 1e (0.05 mmol), 1j (0.05 mmol), and NaI (0.2 mmol); (b) the mixture after adding t-BuOCl (0.1 mmol).
Scheme 7. Plausible Reaction Mechanism
Scheme 8. Oxidation of Hydrazine 5 with t-BuOI
through an oxidative dimerization of aromatic amines under metal-
free and mild conditions. This efficient, low energy-consuming,
and straightforward method allowed us easy access to diverse
azobenzenes including heteroaromatic azo compounds, which
would have high degree of potential for the use as various
functional molecules. Furthermore, mechanistic aspects of this
new oxidative dimerization have been elucidated.
would be deprotonated by t-BuO− to produce monoiodinated
aniline C. The following iodination of C would afford N,N-
diiodoaniline D in a similar manner. It should be noted that the
second iodination of C proceed more preferentially than the
monoiodination of the electron-poorer aniline. This is possibly
because the nucleophilicity of monoiodinated intermediate C is
higher than that of the unreacted electron-deficient aniline as the
result of slight pyramidalization of the N-center partly facilitated
by steric repulsion.34 The diiodinated aniline D would then serve
as an electrophile to form the N−N single bond to afford E that
accompanies liberation of HI. Lastly, elimination of another
equivalent of HI would give aromatic azo product, which was
supported by the experiment illustrated in Scheme 8. Liberated HI
would be trapped by 2 equiv of t-BuOI, thus resulting in I2 and
t-BuOH as discussed in the early part of this section.
EXPERIMENTAL SECTION
■
General Experimental Methods. All reactions were carried out
under a nitrogen atmosphere. 1H and 13C NMR spectra were recorded
on a NMR spectrometer (1H NMR, 270 or 400 MHz; 13C NMR, 68
or 100 MHz) using tetramethylsilane as an internal standard. 15N
NMR spectra were recorded on a NMR spectrometer (15N NMR,
40 MHz) using liquid ammonia as an external standard. 19F NMR
spectra were recorded on a NMR spectrometer (19F NMR, 376 MHz)
using benzotrifluoride as an internal standard. Products were purified
by chromatography on silica gel (200−400 mesh) or aluminum oxide
(active stage I, 0.063−0.200 mm). Analytical thin-layer chromatog-
raphy (TLC) was performed on precoated silica gel glass plates (silica
gel, 0.25 mm thickness). Compounds were visualized with UV lamp or
treatment with an ethanolic solution of phosphomolybdic acid
followed by heating.
Materials. Aromatic Amines except for 1y and 3b were purchased
from commercial sources and distilled or recrystallized before using.
Aromatic amines 1x35, 1y36 and 3b22b were prepared according to the
literature. Sodium iodide and tert-butyl hypochlorite were purchased
from commercial sources and used as received. N-Iodophthalimide
CONCLUSION
■
In summary, we have developed a new synthetic method for
both of symmetric and unsymmetric aromatic azo compounds
J
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(NIPI)37 and N-iodosaccharin (NIsac)38 were prepared according to
the literature. All other reagents were commercially available and used
as received.
148.8 (d, J = 2.2 Hz), 164.2 (d, J = 251.7 Hz); IR (ATR) ν 2939, 1729,
1589, 1496, 1228, 1138, 839, 752 cm−1; MS (EI) m/z (relative intensity, %)
218 ([M]+, 40), 95 ([C6H4F]+, 100), 123 ([N2C6H4F]+, 25); HRMS
(EI) m/z calcd for C12H8F2N2 (M) 218.0656, found 218.0660.
(E)-1,2-Bis(4-chlorophenyl)diazene (2ff). Spectroscopic data
were in agreement with those previously reported.13d Purified by
silica gel column chromatography (hexane/EtOAc 95:5); yellow solid
(59.0 mg, 96%); mp 182.0−184.5 °C; Rf 0.50 (hexane/EtOAc 9:1);
1H NMR (270 MHz, CDCl3) δ 7.48 (d, 4H, J = 8.9 Hz), 7.87 (d, 4H,
J = 8.9 Hz); 13C NMR (68 MHz, CDCl3) δ 124.1, 129.3, 137.1, 150.6;
IR (ATR) ν 1571, 1475, 1103, 1082, 1002, 842, 825, 715 cm−1; MS
(EI) m/z (relative intensity, %) 250 ([M]+, 31), 111 ([C6H4Cl]+,
100), 139 ([N2C6H4Cl]+, 38); HRMS (EI) m/z calcd for C12H8Cl2N2
(M) 250.0065, found 250.0055.
(E)-1,2-Bis(4-bromophenyl)diazene (2gg). Spectroscopic data
were in agreement with those previously reported.13d Purified by basic
alumina column chromatography (hexane/EtOAc 95:5); red solid
(70.7 mg, 83%); mp 201.3−203.7 °C; Rf 0.50 (hexane/EtOAc 9:1);
1H NMR (270 MHz, CDCl3) δ 7.65 (d, 4H, J = 8.1 Hz), 7.79 (d, 4H,
J = 8.1 Hz); 13C NMR (68 MHz, CDCl3) δ 124.3, 125.7, 132.3, 151.0;
IR (ATR) ν 1726, 1568, 1469, 1396, 1269, 1062, 1004, 833, 709 cm−1;
MS (EI) m/z (relative intensity, %) 340 ([M]+, 33), 155 ([C6H4Br]+,
100), 183 ([N2C6H4Br]+, 61); HRMS (EI) m/z calcd for C12H8Br2N2
(M) 337.9054, found 337.9053.
Typical Procedure for Comparative Study of Halogen-
Containing Oxidants (Table 1). To a solution of p-toluidine
(0.5 mmol, 53.6 mg) in diethyl ether (3 mL) was added halogen-containing
oxidant (1.0 mmol) under N2 atmosphere at room temperature. The
mixture was stirred for 1 h and quenched with aqueous Na2S2O3
(1.0 M, 10 mL), and the solution was extracted with CH2Cl2 (20 mL × 3).
The combined organic extracts were dried over Na2SO4 and concentrated
under vacuum to give a crude product. The yield of product was
calculated by 1H NMR integration of the crude product using 1,1,2,2-
tetrachloroethane as an internal standard.
Typical Procedure for the Synthesis of Symmetric Azo
Compounds Using t-BuOI (Table 2 and 3). To a mixture of
aromatic amine (0.5 mmol) and NaI (1.0 mmol, 150.0 mg) in an
appropriate solvent (3 mL) was added t-BuOCl (1.0 mmol, 108.6 mg)
under N2 atmosphere at the appropriate temperature. The mixture was
stirred for the indicated time and quenched with aqueous Na2S2O3
(1.0 M, 10 mL), and the solution was extracted with CH2Cl2 (20 mL × 3).
The combined organic extracts were dried over Na2SO4 and concentrated
under vacuum to give the crude product. Purification by flash column
chromatography on silica gel (eluent: ethyl acetate in hexane) gave
homodimerized product.
(E)-1,2-Diphenyldiazene (2aa). Spectroscopic data were in
agreement with those previously reported.13d Purified by silica gel
column chromatography (hexane/EtOAc 99:1); red solid (43.0 mg,
95%); mp 67.3−68.2 °C; Rf 0.53 (hexane/EtOAc 9:1); 1H NMR
(270 MHz, CDCl3) δ 7.41−7.53 (m, 6H), 7.89−7.94 (m, 4H); 13C
NMR (68 MHz, CDCl3) δ 122.7, 129.0, 130.9, 152.5; IR (ATR) ν
1580, 1481, 1450, 1298, 1068, 926, 773 cm−1; MS (EI) m/z (relative
intensity, %) 182 ([M]+, 57), 77 ([C6H5]+, 100), 105 ([N2C6H5]+,
26); HRMS (EI) m/z calcd for C12H10N2 (M) 182.0844, found
182.0841.
(E)-1,2-Bis(4-iodophenyl)diazene (2hh). Spectroscopic data
were in agreement with those previously reported.34 Purified by silica
gel column chromatography (hexane/EtOAc 95:5); red solid (95.1 mg,
1
88%); mp 242.4−244.8 °C; Rf 0.50 (hexane/EtOAc 9:1); H NMR
(270 MHz, CDCl3) δ 7.64 (d, 4H, J = 8.6 Hz), 7.86 (d, 4H, J = 8.6 Hz);
13C NMR (68 MHz, CDCl3) δ 98.1, 124.5, 138.4, 151.8; IR (ATR) ν
1560, 1467, 1390, 1296, 1278, 1095, 1049, 1001, 810, 713 cm−1; MS
(EI) m/z (relative intensity, %) 434 ([M]+, 72), 203 ([C6H4I]+, 100),
231 ([N2C6H4I]+, 53); HRMS (EI) m/z calcd for C12H8I2N2 (M)
433.8777, found 433.8776.
(E)-1,2-Di-p-tolyldiazene (2bb). Spectroscopic data were in
agreement with those previously reported.13d Purified by silica gel
column chromatography (hexane/EtOAc 99:1); yellow solid (51.2 mg,
(E)-Diethyl 4,4′-(Diazene-1,2-diyl)dibenzoate (2ii). Spectro-
scopic data were in agreement with those previously reported.13d
Purified by silica gel column chromatography (hexane/EtOAc 9:1);
red solid (77.9 mg, 95%); mp 139.7−142.6 °C; Rf 0.26 (hexane/
EtOAc 9:1); 1H NMR (270 MHz, CDCl3) δ 1.44 (t, 6H, J = 7.0 Hz),
4.42 (q, 4H, J = 7.0 Hz), 7.98 (d, 4H, J = 8.6 Hz), 8.22 (d, 4H, J = 8.6
Hz,); 13C NMR (68 MHz, CDCl3) δ 14.4, 61.4, 122.8, 130.5, 132.6,
154.7, 165.8; IR (ATR) ν 1711, 1265, 1095, 1006, 868, 779, 700 cm−1;
MS (EI) m/z (relative intensity, %) 326 ([M]+, 33), 149 ([C6H4CO2Et]+,
100), 177 ([N2C6H4 CO2Et]+, 13); HRMS (EI) m/z calcd for
C18H18N2O4 (M) 326.1267, found 326.1269.
(E)-1,2-Bis(4-acetylphenyl)diazene (2jj). Spectroscopic data
were in agreement with those previously reported.8b Purified by
basic alumina column chromatography (hexane/EtOAc 8:2); red solid
(60.7 mg, 91%); mp 213.0−215.5 °C; Rf 0.16 (hexane/EtOAc 9:1);
1H NMR (270 MHz, CDCl3) δ 2.68 (s, 6H), 8.01 (d, 4H, J = 8.6 Hz),
8.13 (d, 4H, J = 8.6 Hz); 13C NMR (68 MHz, CDCl3) δ 27.0, 123.1,
129.3, 138.7, 154.6, 197.2; IR (ATR) ν 1672, 1404, 1354, 1307, 1258,
1223, 1109, 1006, 961, 856, 837 cm−1; MS (EI) m/z (relative intensity, %)
266 ([M]+, 58), 119 ([C6H4COCH3]+, 100), 147 ([N2C6H4COCH3]+,
14); HRMS (EI) m/z calcd for C16H14N2O2 (M) 266.1055, found
266.1053.
(E)-4,4′-(Diazene-1,2-diyl)dibenzonitrile (2kk). Spectroscopic
data were in agreement with those previously reported.8c Purified by
silica gel column chromatography (hexane/EtOAc 7:3); red solid
(51.4 mg, 89%); mp 277.8−278.2 °C; Rf 0.05 (hexane/EtOAc 9:1);
1H NMR (270 MHz, CDCl3) δ 7.86 (d, 4H, J = 8.6 Hz), 8.04 (d, 4H,
J = 8.6 Hz); 13C NMR (68 MHz, CDCl3) δ 115.1, 118.2, 123.7, 133.4,
153.9; IR (ATR) ν 2924, 2226, 1489, 1408, 1294, 1098, 1011, 851,
839 cm−1; MS (EI) m/z (relative intensity, %) 232 ([M]+, 49), 102
([C6H4CN]+, 100), 130 ([N2C6H4CN]+, 22); HRMS (EI) m/z calcd
for C14H8N4 (M) 232.0749, found 232.0748.
1
97%); mp 137.6−140.9 °C; Rf 0.48 (hexane/EtOAc 9:1); H NMR
(270 MHz, CDCl3) δ 2.42 (s, 6H), 7.30 (d, 4H, J = 8.4 Hz), 7.81 (d,
4H, J = 8.4 Hz); 13C NMR (68 MHz, CDCl3) δ 21.6, 122.6, 129.6,
141.1, 150.7; IR (ATR) ν 2922, 1597, 1500, 1151, 1109, 823 cm−1;
MS (EI) m/z (relative intensity, %) 210 ([M]+, 37), 91 ([C6H4CH3]+,
100), 119 ([N2C6H4CH3]+, 15); HRMS (EI) m/z calcd for C14H14N2
(M) 210.1157, found 210.1153.
(E)-1,2-Bis(4-methoxyphenyl)diazene (2cc). Spectroscopic data
were in agreement with those previously reported.13d Purified by silica
gel column chromatography (hexane/EtOAc 9:1); yellow solid (52.8 mg,
1
87%); mp 154.6−156.3 °C; Rf 0.25 (hexane/EtOAc 9:1); H NMR
(270 MHz, CDCl3) δ 3.88 (s, 6H), 6.99 (d, 4H, J = 8.9 Hz), 7.87 (d,
4H, J = 8.9 Hz); 13C NMR (68 MHz, CDCl3) δ 55.6, 114.1, 124.2,
146.9, 161.4; IR (ATR) ν 2920, 1728, 1575, 1240, 1139, 1101, 1022,
813 cm−1; MS (EI) m/z (relative intensity, %) 242 ([M]+, 88), 107
([C6H4OCH3]+, 100), 135 ([N2C6H4OCH3]+, 41); HRMS (EI) m/z
calcd for C14H14N2O2 (M) 242.1055, found 242.1059.
(E)-4,4′-(Diazene-1,2-diyl)bis(N,N-dimethylaniline) (2dd).
Spectroscopic data were in agreement with those previously
reported.8b Purified by silica gel column chromatography (hexane/
EtOAc 9:1); red solid (40.3 mg, 60%); mp 264.7−265.2 °C (dec.); Rf
1
0.38 (hexane/EtOAc 8:2); H NMR (400 MHz, CDCl3) δ 3.06 (s,
12H), 6.76 (d, 4H, J = 9.2 Hz), 7.81 (d, 4H, J = 9.2 Hz); 13C NMR
(100 MHz, CDCl3) δ 40.4, 111.8, 124.0, 144.1, 151.5; IR (ATR) ν
2916, 1726, 1591, 1362, 1146, 1130, 894 cm−1; MS (EI) m/z (relative
intensity, %) 268 ([M]+, 100), 120 ([C6H4N(CH3)2]+, 79); HRMS
(EI) m/z calcd for C16H20N4 (M) 268.1688, found 268.1689.
(E)-1,2-Bis(4-fluorophenyl)diazene (2ee). Spectroscopic data
were in agreement with those previously reported.13d Purified by silica
gel column chromatography (hexane/EtOAc 99:1); yellow solid (52.1 mg,
1
95%); mp 97.1−99.8 °C; Rf 0.56 (hexane/EtOAc 9:1); H NMR
(E)-1,2-Bis(4-nitrophenyl)diazene (2ll). Spectroscopic data were
in agreement with those previously reported.39 Purified by basic alumina
column chromatography (hexane/EtOAc 7:3); red solid (54.3 mg,
(270 MHz, CDCl3) δ 7.15−7.21 (m, 4H), 7.88−7.93 (m, 4H); 13C
NMR (68 MHz, CDCl3) δ 116.0 (d, J = 22.8 Hz), 124.7 (d, J = 9.0 Hz),
K
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1
1
79%); mp 223.3−225.4 °C; Rf 0.10 (hexane/EtOAc 9:1); H NMR
(270 MHz, CDCl3) δ 8.11 (d, 4H, J = 8.9 Hz), 8.43 (d, 4H, J = 8.9
Hz); 13C NMR (68 MHz, CDCl3) δ 123.8, 124.7, 149.2, 154.8; IR
(ATR) ν 1608, 1533, 1344, 1319, 1209, 1105, 1002, 862, 806, 758 cm−1;
MS (EI) m/z (relative intensity, %) 272 ([M]+, 49), 122 ([C6H4NO2]+,
100), 150 ([N2C6H4NO2]+, 61); HRMS (EI) m/z calcd for C12H8N4O4
(M) 272.0546, found 272.0547.
(109.3 mg, 94%); mp 115.2−117.2 °C; Rf 0.40 (hexane); H NMR
(270 MHz, CDCl3) δ 8.06 (s, 2H), 8.46 (s, 4H); 13C NMR (68 MHz,
CDCl3) δ 122.9 (q, J = 272.9 Hz), 123.4 (q, J = 2.8 Hz), 125.2 (m),
133.2 (q, J = 34.1 Hz), 152.1; IR (ATR) ν 1373, 1277, 1262,
1165, 1105, 1055, 935, 907, 847, 729 cm−1; MS (EI) m/z (relative
intensity, %) 454 ([M]+, 20), 213 ([C6H4(CF3)2]+, 100), 241
([N2C6H4(CF3)2]+, 9); HRMS (EI) m/z calcd for C16H6F12N2 (M)
454.0339, found 454.0340.
(E)-4,4′-Bis(phenylazo)azobenzene (2 mm). Spectroscopic data
were in agreement with those previously reported.40 Purified by basic
alumina column chromatography (hexane/EtOAc 5:5); brown solid
(65.1 mg, 67%); mp 237.0−237.8 °C; Rf 0.45 (hexane/EtOAc 8:2);
1H NMR (400 MHz, CDCl3) δ 8.13 (d, 4H, J = 8.8, Hz), 8.10 (d, 4H,
J = 8.8, Hz), 7.98 (d, 4H, J = 6.8 Hz), 7.54 (m, 6H); IR (ATR) ν 3065,
3044, 1942, 1692, 1587, 1306, 1213, 854, 759 cm−1; MS (EI) m/z
(relative intensity, %) 390 ([M]+, 100), 105 ([C6H5N2]+, 41), 181
([C6H5N2C6H4]+, 69), 285 ([C6H5N2C6H4N2C6H4]+, 49); HRMS
(EI) m/z calcd for C24H18N6 (M) 390.1593, found 390.1595.
(E)-1,2-Bis(3-chlorophenyl)diazene (2nn). Spectroscopic data
were in agreement with those previously reported.34 Purified by silica
gel column chromatography (hexane/EtOAc 95:5); yellow solid
(53.8 mg, 86%); mp 100.2−101.6 °C; Rf 0.50 (hexane/EtOAc 9:1);
1H NMR (270 MHz, CDCl3) δ 7.43−7.45 (m, 4H), 7.70−7.88 (m,
4H); 13C NMR (68 MHz, CDCl3) δ 121.8, 122.5, 130.1, 131.1, 135.1,
152.9; IR (ATR) ν 1584, 1566, 1462, 1198, 1067, 885, 790 cm−1; MS
(EI) m/z (relative intensity, %) 250 ([M]+, 13), 111 ([C6H4Cl]+,
100), 139 ([N2C6H4Cl]+, 18); HRMS (EI) m/z calcd for C12H8Cl2N2
(M) 250.0065, found 250.0061.
(E)-1,2-Bis(3-nitrophenyl)diazene (2oo). Spectroscopic data
were in agreement with those previously reported.41 Purified by basic
alumina column chromatography (hexane/EtOAc 8:2); orange solid
(53.3 mg, 78%); mp 149.8−151.6 °C; Rf 0.14 (hexane/EtOAc 9:1);
1H NMR (270 MHz, CDCl3) δ 7.78 (dd, 2H, J = 8.1, 8.1 Hz), 8.34
(dd, 2H, J = 1.1, 8.1 Hz), 8.40 (dd, 2H, J = 1.1, 8.1 Hz), 8.79 (s, 2H);
13C NMR (68 MHz, CDCl3) δ 117.1, 125.9, 129.6, 130.2, 148.9, 152.2;
IR (ATR) ν 1528, 1344, 1312, 1070, 918, 808, 741 cm−1; MS (EI)
m/z (relative intensity, %) 272 ([M]+, 39), 122 ([C6H4NO2]+, 100),
150 ([N2C6H4NO2]+, 63); HRMS (EI) m/z calcd for C12H8N4O4 (M)
272.0546, found 272.0544.
(E)-1,2-Bis(pentafluorophenyl)diazene (2tt). Spectroscopic
data were in agreement with those previously reported.42 Purified by
silica gel column chromatography (hexane/EtOAc 99:1); yellow solid
(60.7 mg, 67%); mp 139.6−142.1 °C; Rf 0.55 (hexane/EtOAc 9:1);
19F NMR (376 MHz, CDCl3) δ −150.8 (m, 2F), −151.1 (m, 1F),
−163.7 (m, 2F); IR (ATR) ν 1641, 1504, 1408, 1319, 1146, 999,
976 cm−1; MS (EI) m/z (relative intensity, %) 362 ([M]+, 43), 167
([C6F5]+, 100), 195 ([N2C6F5]+, 33); HRMS (EI) m/z calcd for
C12F10N2 (M) 361.9902, found 361.9904.
(E)-1,2-Bis(1-methyl-1H-pyrazol-3-yl)diazene (2uu). Purified
by silica gel column chromatography (EtOAc); yellow solid (39.5 mg,
1
83%); mp 200.8−201.6 °C; Rf 0.28 (EtOAc); H NMR (400 MHz,
CDCl3) δ 4.00 (s, 6H), 6.68 (d, 2H, J = 2.4 Hz), 7.36 (d, 2H, J = 2.4
Hz); 13C NMR (100 MHz, CDCl3) δ 39.6, 95.3, 131.8, 164.0; IR
(ATR) ν 3125, 2924, 1375, 1303, 1209, 869 cm−1; MS (EI) m/z
(relative intensity, %) 190 ([M]+, 100), 109 ([N2C4H5N2]+, 95);
HRMS (EI) m/z calcd for C8H10N6 (M) 190.0967, found 190.0966.
(E)-1,2-Bis(5-methylisoxazol-3-yl)diazene (2vv). Spectroscopic
data were in agreement with those previously reported.20c Purified by
basic alumina column chromatography (hexane/EtOAc 95:5); yellow
solid (36.5 mg, 76%); mp 212.2−212.7 °C; Rf 0.38 (hexane/EtOAc
1
9:1); H NMR (400 MHz, CDCl3) δ 2.54 (s, 6H), 6.42 (s, 2H); 13C
NMR (100 MHz, CDCl3) δ 12.8, 92.0, 172.0, 173.8; IR (ATR) ν
3145, 1599, 1466, 1433, 1413, 1240, 1022, 1001, 929, 819, 740 cm−1;
MS (EI) m/z (relative intensity, %) 192 ([M]+, 58), 110
([N2C4H4NO]+, 100); HRMS (EI) m/z calcd for C8H8N4O2 (M)
192.0647, found 192.0644.
(E)-1,2-Bis(1-methyl-1H-benzo[d]imidazol-2-yl)diazene (2ww).
Purified by basic alumina column chromatography (CHCl3/MeOH
99:1); red solid (55.4 mg, 76%); mp 282.9−283.3 °C; Rf 0.38 (CHCl3/
MeOH 99:1); 1H NMR (400 MHz, CDCl3) δ 4.32 (s, 6H), 7.38−7.51
(m, 6H), 7.96 (d, 2H, J = 7.6 Hz); 13C NMR (100 MHz, CDCl3) δ
30.3, 110.4, 122.4, 124.8, 125.4, 136.6, 142.4, 155.8; IR (ATR) ν 3051,
1573, 1483, 1458, 1325, 1246 cm−1; FAB-MS m/z 291 ([M]++1);
HRMS (FAB) m/z calcd for C16H15N6 (M) 291.1358, found 291.1361.
(E)-2,2′-Azobenzothiazole (2xx). Purified by silica gel column
chromatography (hexane/EtOAc 7:3); orange solid (53.4 mg, 72%); mp
(E)-1,2-Bis([1,1′-biphenyl]-2-yl)diazene (2pp). Purified by silica
gel column chromatography (hexane/EtOAc 95:5); orange solid
(36.5 mg, 44%); mp 133.5 °C; Rf 0.40 (hexane/EtOAc 9:1); 1H NMR
(270 MHz, CDCl3) δ 7.26−7.57 (m, 18H); 13C NMR (68 MHz,
CDCl3) δ 116.3, 127.2, 127.6, 130.0, 130.6, 130.7, 130.8, 138.8, 141.4,
149.7; IR (ATR) ν 3048, 1586, 1470, 768, 732, 723 cm−1; MS (EI)
m/z (relative intensity, %) 334 ([M]+, 60), 153 ([C6H4Ph]+, 100), 181
([N2C6H4Ph]+, 25); HRMS (EI) m/z calcd for C24H18N2 (M)
334.1470, found 334.1471.
1
293.7−294.6 °C; Rf 0.10 (hexane/EtOAc 9:1); H NMR (270 MHz,
CDCl3) δ 7.58 (m, 4H), 7.97 (m, 2H), 8.26 (m, 2H); 13C NMR (68
MHz, CDCl3) δ 122.6, 125.8, 127.8, 128.9, 135.4, 153.2, 173.4; IR
(ATR) ν 1548, 1474, 1452, 1313, 1244, 1192, 1153, 1115, 893 cm−1;
MS (EI) m/z (relative intensity, %) 296 ([M]+, 3), 268 ([M − N2]+,
100), 130 ([C7H4NS]+, 43); HRMS (EI) m/z calcd for C14H8N4S2 (M)
296.0190, found 296.0193.
(E)-2,2′-(Diazene-1,2-diyl)dibenzonitrile (2qq). Purified by
basic alumina column chromatography (hexane/EtOAc 7:3); red
solid (42.1 mg, 73%); mp 233.1−234.7 °C; Rf 0.05 (hexane/EtOAc
1
9:1); H NMR (270 MHz, CDCl3) δ 7.65 (ddd, 2H, J = 1.4, 7.6, 7.6
Hz), 7.75 (ddd, 2H, J = 1.6, 7.6, 7.6 Hz), 7.89 (dd, 2H, J = 1.6, 7.6
Hz), 8.06 (dd, 2H, J = 1.4, 7.6 Hz); 13C NMR (68 MHz, CDCl3) δ
114.8, 116.4, 116.8, 132.3, 133.5, 152.4; IR (ATR) ν 2232, 1589, 1481,
1227, 773, 743 cm−1; MS (EI) m/z (relative intensity, %) 232 ([M]+,
23), 102 ([C6H4CN]+, 100), 130 ([N2C6H4CN]+, 34); HRMS (EI)
m/z calcd for C14H8N4 (M) 232.0759, found 232.0754.
(E)-1,2-Bis-benzothiazol-6-yl-diazene (2yy). Purified by silica
gel column chromatography (CHCl3/MeOH 100:0 to 8.2); yellow
solid (46.2 mg, 62%); mp 250.2−251.1 °C; Rf 0.23 (CHCl3/MeOH
1
9:1); H NMR (400 MHz, CDCl3) δ 8.19 (dd, 2H, J = 2.0, 8.8 Hz),
8.27 (d, 2H, J = 8.8 Hz), 8.59 (d, 2H, J = 2.0 Hz), 9.13 (s, 2H); 13C
NMR (100 MHz, CDCl3) δ 117.7, 121.1, 124.1, 134.7, 150.2, 155.0,
156.4; IR (ATR) ν 3064, 1585, 1466, 1398, 1290, 889, 846 cm−1; MS
(EI) m/z (relative intensity, %) 296 ([M]+, 49), 134 ([C7H4NS]+,
100), 162 ([N2C7H4NS]+, 32); HRMS (EI) m/z calcd for C14H8N4S2
(M) 296.0190, found 296.0192.
(E)-9,9′-Diethyl-3,3′-azocarbazole (2zz). Spectroscopic data were
in agreement with those previously reported.43 Purified by basic
alumina column chromatography (hexane/EtOAc 9:1); yellow solid
(72.8 mg, 70%); mp 213.1−2136. °C; Rf 0.28 (hexane/EtOAc 8:2);
1H NMR (400 MHz, CDCl3) δ 1.50 (t, 6H, J = 7.2 Hz), 4.44 (q, 4H,
J = 7.2 Hz), 7.31 (t, 2H, J = 6.8 Hz), 7.45−7.53 (m, 6H), 8,21 (m,
4H), 8.75 (d, 2H, J = 2.0 Hz); 13C NMR (100 MHz, CDCl3) δ 13.9,
37.8, 108.6, 108.9, 116.0, 119.5, 120.7, 120.8, 123.3, 123.6, 126.1,
(E)-1,2-Bis(3,4-dimethylphenyl)diazene (2rr). Purified by silica
gel column chromatography (hexane/EtOAc 99:1); yellow solid
1
(53.3 mg, 89%); mp 155.2−157.8 °C; Rf 0.50 (hexane/EtOAc 9:1); H
NMR (270 MHz, CDCl3) δ 2.31 (s, 6H), 2.34 (s, 6H), 7.23 (d, 2H,
J = 7.8 Hz), 7.65 (d, 2H, J = 7.8 Hz), 7.68 (s, 2H); 13C NMR (68
MHz, CDCl3) δ 19.9, 19.9, 120.7, 123.2, 130.2, 137.4, 139.9, 151.2; IR
(ATR) ν 1602, 1443, 1242, 1101, 1022, 883, 827, 712 cm−1; MS (EI)
m/z (relative intensity, %) 238 ([M]+, 45), 105 ([C6H4(CH3)2]+, 81),
133 ([N2C6H4(CH3)2]+, 16); HRMS (EI) m/z calcd for C16H18N2
(M) 238.1470, found 238.1469.
(E)-1,2-Bis(3,5-bis(trifluoromethyl)phenyl)diazene (2ss). Pu-
rified by silica gel column chromatography (hexane); yellow solid
L
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140.6, 141.2, 146.5; IR (ATR) ν 2972, 1593, 1277, 1323, 1229, 1117,
746 cm−1; MS (EI) m/z (relative intensity, %) 416 ([M]+, 57), 194
([C14H12N]+, 100); HRMS (EI) m/z calcd for C28H24N4 (M)
416.2001, found 416.2002.
901, 828, 810, 739, 710 cm−1; MS (EI) m/z (relative intensity, %) 241
([M]+, 27), 91 ([C6H4CH3]+, 100), 119 ([N2C6H4CH3]+, 23); HRMS
(EI) m/z calcd for C13H11N3O2 (M) 241.0851, found 241.0848.
(E)-1-(3,5-Bis(trifluoromethyl)phenyl)-2-p-tolyldiazene (2bs).
Purified by silica gel column chromatography (hexane/EtOAc 99:1
to 9:1); orange solid (54.6 mg, 66%); mp 82.0−84.4 °C; Rf 0.28
Typical Procedure for the Synthesis of Asymmetric Azo
Compounds Using t-BuOI (Table 4 and 5). To a mixture of two
aromatic amines (Ar1NH2 and Ar2NH2, 0.25 mmol for each) and NaI
(1.0 mmol, 150.0 mg) in an appropriate solvent (3 mL), was added
t-BuOCl (1.0 mmol, 108.6 mg) under N2 atmosphere at the appropriate
temperature. The mixture was stirred for the indicated time and
quenched with aqueous Na2S2O3 (1.0 M, 10 mL), and the solution
was extracted with CH2Cl2 (20 mL × 3). The combined organic
extracts were dried over Na2SO4 and concentrated under vacuum to
give the crude product. Purification by flash column chromatography
on silica gel (eluent: ethyl acetate in hexane) gave cross-dimerized
product.
(E)-Ethyl 4-(p-Tolyldiazenyl)benzoate (2bi). Spectroscopic data
were in agreement with those previously reported.13d Purified by silica
gel column chromatography (hexane/EtOAc 99:1 to 7:3); yellow solid
(41.3 mg, 62%); mp 100.6−101.3 °C; Rf 0.43 (hexane/EtOAc 9:1);
1H NMR (270 MHz, CDCl3) δ 1.43 (t, 3H, J = 7.0 Hz), 2.45 (s, 3H),
4.42 (q, 2H, J = 7.0 Hz), 7.32 (d, 2H, J = 8.4 Hz), 7.87 (d, 2H, J = 8.4
Hz), 7.92 (d, 2H, J = 8.6 Hz), 8.19 (d, 2H, J = 8.6 Hz); 13C NMR
(68 MHz, CDCl3) δ 14.4, 21.6, 61.2, 122.4, 123.1, 129.7, 130.4, 131.8,
142.3, 150.6, 155.1, 165.9; IR (ATR) ν 2922, 1715, 1601, 1265, 1103,
1094, 1008, 866, 822, 773, 709 cm−1; MS (EI) m/z (relative inten-
sity, %) 268 ([M]+, 53), 91 ([C6H4CH3]+, 100), 119 ([N2C6H4CH3]+,
33), 149 ([C6H4CO2Et]+, 25); HRMS (EI) m/z calcd for C16H16N2O2
(M) 268.1212, found 268.1214.
(E)-1-(4-Acetylphenyl)-2-p-tolyldiazene (2bj). Purified by silica
gel column chromatography (hexane/EtOAc 99:1 to 7:3); red solid
(34.7 mg, 58%); mp 128.7−130.0 °C; Rf 0.18 (hexane/EtOAc 9:1);
1H NMR (270 MHz, CDCl3) δ 2.45 (s, 3H), 2.66 (s, 3H), 7.33 (d,
2H, J = 8.4 Hz), 7.86 (d, 2H, J = 8.4 Hz), 7.95 (d, 2H, J = 8.6 Hz),
8.10 (d, 2H, J = 8.6 Hz); 13C NMR (68 MHz, CDCl3) δ 21.6, 26.8,
122.7, 123.2, 129.3, 129.8, 138.1, 142.5, 150.7, 155.1, 197.5; IR (ATR) ν
1676, 1595, 1354, 1263, 1003, 962, 853, 820, 707 cm−1; MS (EI)
m/z (relative intensity, %) 238 ([M]+, 38), 91 ([C6H4CH3]+, 100),
119 ([N2C6H4CH3]+, 35); HRMS (EI) m/z calcd for C15H14N2O (M)
238.1106, found 238.1109.
1
(hexane); H NMR (270 MHz, CDCl3) δ 2.45 (s, 3H), 7.34 (d, 2H,
J = 8.1 Hz), 7.87 (d, 2H, J = 8.1 Hz), 7.95 (s, 1H), 8.33 (s, 2H); 13C
NMR (68 MHz, CDCl3) δ 21.6, 122.8 (q, J = 3.3 Hz), 123.1 (q, J =
272.9 Hz), 123.5, 130.0, 132.6 (q, J = 34.1 Hz), 143.4, 150.2, 152.9; IR
(ATR) ν 1600, 1504, 1363, 1275, 1261, 1172, 1124, 899, 828 cm−1;
MS (EI) m/z (relative intensity, %) 332 ([M]+, 31), 91 ([C6H4CH3]+,
100), 119 ([N2C6H4CH3]+, 19), 213 ([C6H4(CF3)2]+, 11); HRMS
(EI) m/z calcd for C15H10F6N2 (M) 332.0748, found 332.0745.
(E)-1-(4-Acetylphenyl)-2-phenyldiazene (2aj). Spectroscopic
data were in agreement with those previously reported.8b Purified by
silica gel column chromatography (hexane/EtOAc 99:1 to 7:3); red
solid (30.0 mg, 54%); mp 102.3−104.7 °C; Rf 0.24 (hexane/EtOAc
1
9:1); H NMR (270 MHz, CDCl3) δ 2.66 (s, 3H), 7.50−7.56 (m,
3H), 7.93−7.99 (m, 4H), 8.10 (d, 2H, J = 8.6 Hz); 13C NMR (68
MHz, CDCl3) δ 26.8, 122.8, 123.1, 129.2, 129.3, 131.7, 138.3, 152.5,
155.0, 197.4; IR (ATR) ν 2924, 1674, 1352, 1259, 961, 839, 771 cm−1;
MS (EI) m/z (relative intensity, %) 224 ([M]+, 100), 77 ([C6H5]+,
97), 105 ([N2C6H5]+, 26), 119 ([C6H4COCH3]+, 57); HRMS (EI)
m/z calcd for C14H12N2O (M) 224.0950, found 224.0952.
(E)-1-(4-Acetylphenyl)-2-(4-nitrophenyl)diazene (2jl). Spec-
troscopic data were in agreement with those previously reported.39
Purified by silica gel column chromatography (hexane/EtOAc 99:1 to
7:3); red solid (48.2 mg, 72%); mp 160.0−161.6 °C; Rf 0.15 (hexane/
1
EtOAc 9:1); H NMR (270 MHz, CDCl3) δ 2.68 (s, 3H), 8.00−8.15
(m, 6H), 8.38 (d, 2H, J = 8.4 Hz); 13C NMR (68 MHz, CDCl3) δ
26.8, 123.4, 123.7, 124.7, 129.4, 139.3, 149.1, 154.5, 155.3, 197.1; IR
(ATR) ν 1681, 1698, 1534, 1341, 1319, 1261, 1215, 1109 cm−1, 860;
MS (EI) m/z (relative intensity, %) 269 ([M]+, 68), 119 ([C6H4COCH3]+,
100), 122 ([C6H4NO2]+, 35), 147 ([N2C6H4 COCH3]+, 29); HRMS (EI)
m/z calcd for C14H11N3O3 (M) 269.0800, found 269.0803.
(E)-1-(4-Acetylphenyl)-2-(4-fluorophenyl)diazene (2ej). Puri-
fied by silica gel column chromatography (hexane/EtOAc 99:1 to
7:3); orange solid (36.8 mg, 61%); mp 111.5−114.1 °C; Rf 0.24
1
(hexane/EtOAc 9:1); H NMR (270 MHz, CDCl3) δ 2.66 (s, 3H),
7.18−7.27 (m, 2H), 7.93−8.02 (m, 4H), 8.08−8.13 (m, 2H); 13C
NMR (68 MHz, CDCl3) δ 26.8, 116.2 (d, J = 22.9 Hz), 122.8, 125.2
(d, J = 9.5 Hz), 129.3, 138.4, 149.0 (d, J = 2.8 Hz), 154.8, 164.8 (d, J =
253.3 Hz), 197.3; IR (ATR) ν 1680, 1591, 1489, 1406, 1358, 1233,
1138, 843 cm−1; MS (EI) m/z (relative intensity, %) 242 ([M]+, 62),
95 ([C6H4F]+, 100), 119 ([C6H4COCH3]+, 41), 123 ([N2C6H4F]+,
36); HRMS (EI) m/z calcd for C14H11FN2O (M) 242.0855, found
242.0855.
(E)-1-(4-Nitrophenyl)-2-p-tolyldiazene (2bl). Spectroscopic
data were in agreement with those previously reported.39 Purified by
silica gel column chromatography (hexane/EtOAc 99:1 to 7:3);
orange solid (38.5 mg, 64%); mp 180.2−181.3 °C; Rf 0.40 (hexane/
EtOAc 9:1); 1H NMR (270 MHz, CDCl3) δ 2.46 (s, 3H), 7.34 (d, 2H,
J = 8.1 Hz), 7.87 (d, 2H, J = 8.1 Hz), 7.99 (d, 2H, J = 8.9 Hz), 8.35 (d,
2H, J = 8.9 Hz); 13C NMR (68 MHz, CDCl3) δ 21.6, 123.1, 123.3,
124.5, 129.7, 143.1, 148.3, 150.4, 155.6; IR (ATR) ν 1605, 1589, 1522,
1339, 1306, 1134, 1105, 858, 826, 754 cm−1; MS (EI) m/z (relative
intensity, %) 241 ([M]+, 34), 91 ([C6H4CH3]+, 100), 119
([N2C6H4CH3]+, 25); HRMS (EI) m/z calcd for C13H11N3O2 (M)
241.0851, found 241.0847.
(E)-1-(4-Acetylphenyl)-2-(4-chlorophenyl)diazene (2fj). Puri-
fied by silica gel column chromatography (hexane/EtOAc 99:1 to
7:3); orange solid (42.0 mg, 65%); mp 149.8−152.3 °C; Rf 0.25
1
(hexane/EtOAc 9:1); H NMR (270 MHz, CDCl3) δ 2.65 (s, 3H),
7.49 (d, 2H, J = 8.6 Hz), 7.88 (d, 2H, J = 8.6 Hz), 7.94 (d, 2H, J = 8.6
Hz), 8.09 (d, 2H, J = 8.6 Hz); 13C NMR (68 MHz, CDCl3) δ 26.8,
122.9, 124.4, 129.3, 129.4, 137.7, 138.4, 150.7, 154.7, 197.3; IR (ATR) ν
1676, 1478, 1404, 1354, 1261, 1086, 1003, 852, 839 cm−1; MS (EI)
m/z (relative intensity, %) 258 ([M]+, 86), 111 ([C6H4Cl]+, 100), 119
([C6H4COMe]+, 69), 139 ([N2C6H4Cl]+, 43); HRMS (EI) m/z calcd
for C14H11ClN2O (M) 258.0560, found 258.0570.
(E)-1-(3-Chlorophenyl)-2-p-tolyldiazene (2bn). Purified by
silica gel column chromatography (hexane/EtOAc 99:1 to 7:3);
orange solid (29.3 mg, 52%); mp 104.3−105.2 °C; Rf 0.45 (hexane/
1
EtOAc 9:1); H NMR (270 MHz, CDCl3) δ 2,43 (s, 3H), 7.30−7.44
(m, 4H), 7.78−7.88 (m, 4H); 13C NMR (68 MHz, CDCl3) δ 21.5,
121.7, 122.2, 123.1, 129.8, 139.1, 130.4, 135.1, 142.2, 150.5, 153.5; IR
(ATR) ν 2924, 1728, 1599, 1454, 1260, 1070, 823, 791, 710 cm−1; MS
(EI) m/z (relative intensity, %) 230 ([M]+, 24), 91 ([C6H4CH3]+,
100), 111 ([C6H4Cl]+, 17), 119 ([N2C6H4CH3]+, 19); HRMS (EI)
m/z calcd for C13H11ClN2 (M) 230.0611, found 230.0608.
(E)-1-(3-Nitrophenyl)-2-p-tolyldiazene (2bo). Purified by silica
gel column chromatography (hexane/EtOAc 99:1 to 7:3); orange
solid (38.0 mg, 60%); mp 113.2−115.9 °C; Rf 0.38 (hexane/EtOAc
9:1); 1H NMR (270 MHz, CDCl3) δ 2.45 (s, 3H), 7.33 (d, 2H, J = 8.4
Hz), 7.67 (dd, 1H, J = 8.1, 8.1 Hz), 7.86 (d, 2H, J = 8.4 Hz), 8.21 (d,
1H, J = 8.1 Hz), 8.28 (d, 1H, J = 8.1 Hz), 8.69 (s, 1H); 13C NMR (68
MHz, CDCl3) δ 21.6, 116.9, 123.3, 124.5, 129.0, 129.8, 129.9, 143.0,
149.0, 150.3, 153.1; IR (ATR) ν 1601, 1584, 1518, 1346, 1146, 1076,
(E)-1-(4-Acetylphenyl)-2-(4-bromophenyl)diazene (2gj). Pu-
rified by silica gel column chromatography (hexane/EtOAc 99:1 to
7:3); orange solid (44.2 mg, 58%); mp 168.3−169.4 °C; Rf 0.24
1
(hexane/EtOAc 9:1); H NMR (270 MHz, CDCl3) δ 2.67 (s, 3H),
7.67 (d, 2H, J = 8.6 Hz), 7.83 (d, 2H, J = 8.6 Hz), 7.96 (d, 2H, J = 8.6
Hz), 8.10 (d, 2H, J = 8.6 Hz); 13C NMR (68 MHz, CDCl3) δ 26.8,
123.0, 124.6, 126.3, 129.4, 132.4, 138.5, 151.2, 154.7, 197.4; IR (ATR) ν
2920, 1668, 1354, 1260, 1067, 1005, 839 cm−1; MS (EI) m/z (relative
intensity, %) 302 ([M]+, 71), 119 ([C6H4COMe]+, 100), 147
([N2C6H4COMe]+, 25), 155 ([C6H4Br]+, 95), 147 ([N2C6H4Br]+, 41);
HRMS (EI) m/z calcd for C14H11BrN2O (M) 302.0055, found 302.0052.
M
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(E)-1-(4-Acetylphenyl)-2-(4-iodophenyl)diazene (2hj). Puri-
fied by silica gel column chromatography (hexane/EtOAc 99:1 to
7:3); red solid (46.3 mg, 53%); mp 190.0−192.3 °C; Rf 0.33 (hexane/
EtOAc 9:1); 1H NMR (270 MHz, CDCl3) δ 2.67 (s, 3H), 7.68 (d, 2H,
J = 8.6 Hz), 7.89 (d, 2H, J = 8.6 Hz), 7.96 (d, 2H, J = 8.6 Hz), 8.11 (d,
2H, J = 8.6 Hz); 13C NMR (68 MHz, CDCl3) δ 26.9, 98.8, 123.0,
124.7, 129.4, 138.5, 138.6, 151.8 154.7, 197.4; IR (ATR) ν 1665, 1354,
1298, 1263, 1003, 828 cm−1; MS (EI) m/z (relative intensity, %) 350
([M]+, 100), 119 ([C6H4COMe]+, 69), 147 ([N2C6H4COMe]+, 17),
203 ([C6H4I]+, 99), 231 ([N2C6H4I]+, 43); HRMS (EI) m/z calcd for
C14H11IN2O (M) 349.9916, found 349.9914.
8.15 (d, 2H, J = 8.8 Hz); 13C NMR (100 MHz, CDCl3) δ 26.8, 29.9, 110.1,
122.2, 123.7, 124.4, 125.0, 129.3, 136.1, 139.3, 142.1, 154.7, 155.2, 197.2; IR
(ATR) ν 1678, 1392, 1355, 1329, 1256, 824 cm−1; MS (EI) m/z (relative
intensity, %) 278 ([M]+, 7), 249 (100); HRMS (EI) m/z calcd for
C16H14N4O (M) 278.1168, found 278.1166.
(E)-2-(3′,5′-Bis(trifluoromethyl)phenyl)-1-methylbenzimida-
zole (2jw). Purified by silica gel column chromatography (hexane/
EtOAc 99:1 to 8:2); orange solid (46.8 mg, 50%); mp 194.7−
195.2 °C; Rf 0.25 (hexane/EtOAc 8:2); 1H NMR (400 MHz, CDCl3)
δ 4.28 (s, 3H), 7.40−7.49 (m, 2H), 7.51 (d, 1H, J = 7.6 Hz), 7.94 (d,
1H, J = 7.6 Hz), 8.06 (s, 1H), 8.55 (s, 2H); 13C NMR (100 MHz,
CDCl3) δ 30.1 (s), 110.3 (s), 122.4 (s), 122.8 (q, J = 271.7 Hz), 123.4
(q, J = 3.3 Hz), 124.8 (s), 125.0 (m), 125.6 (s), 132.9 (q, J = 33.7 Hz),
136.3(s), 142.1 (s), 153.1 (s), 154.3 (s); IR (ATR) ν 1369, 1278,
1168, 1120, 901 cm−1; MS (EI) m/z (relative intensity, %) 372 ([M]+,
18), 213 ([C6H4(CF3)2]+, 37), 343 (100); HRMS (EI) m/z calcd for
C16H10F6N4 (M) 372.0810, found 372.0809.
(E)-1-(Benzothiazol-2-yl)-2-p-tolyldiazene (2bx). Purified by
silica gel column chromatography (hexane/EtOAc 99:1 to 7:3); orange
solid (53.4 mg, 72%); mp 183.5−184.0 °C; Rf 0.40 (hexane/EtOAc
9:1); 1H NMR (270 MHz, CDCl3) δ 2.45 (s, 3H), 7.30 (d, 2H, J = 8.1
Hz), 7.49 (m, 2H), 7.88 (dd, 1H, J = 1.1, 7.3 Hz), 7.98 (d, 2H, J = 8.1
Hz), 8.17 (dd, 1H, J = 1.4, 7.3 Hz); 13C NMR (68 MHz, CDCl3) δ 21.8,
122.3, 124.4, 124.8, 126.6, 127.3, 130.1, 134.3, 144.9, 149.8, 152.6,
175.9; IR (ATR) ν 1730, 1597, 1494, 1421, 1147, 815, 758, 723 cm−1;
MS (EI) m/z (relative intensity, %) 253 ([M]+, 14), 91 ([C6H4CH3]+,
100), 119 ([N2C6H4CH3]+, 10); HRMS (EI) m/z calcd for C14H11N3S
(M) 253.0674, found 253.0674.
(E)-6-(p-Tolyldiazenyl)benzothiazole (2by). Purified by silica
gel column chromatography (hexane/EtOAc 99:1 to 7:3); orange
solid (27.8 mg, 44%); mp 135.6−136.0 °C; Rf 0.38 (hexane/EtOAc
7:3); 1H NMR (400 MHz, CDCl3) δ 2.44 (s, 3H), 7.32 (d, 2H, J = 8.0
Hz), 7.86 (d, 2H, J = 8.0 Hz), 8.12 (dd, 1H, J = 2.0, 8.8 Hz), 8.22 (d,
1H, J = 8.8 Hz), 8.17 (dd, 1H, J = 1.4, 7.3 Hz), 8.50 (d, 1H, J = 2.0
Hz), 9.07 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 21.6, 117.0, 121.1,
123.0, 123.9, 129.8 (2), 141.9, 150.3, 150.6, 154.6, 156.1; IR (ATR) ν
3049, 1599, 1502, 1429, 1408, 1330, 1225, 846, 825 cm−1; MS (EI)
m/z (relative intensity, %) 253 ([M]+, 78), 91 ([C6H4CH3]+, 100),
134 ([C7H4NS]+, 74); HRMS (EI) m/z calcd for C14H11N3S (M)
253.0674, found 253.0676.
Procedure for the Gram-Scale Synthesis of 2ii (Scheme 3).
To a mixture of ethyl 4-aminobenzoate (10 mmol, 1.65 g) and NaI
(20 mmol, 3.00 g) in Et2O (60 mL) was added t-BuOCl (20 mmol,
2.17 g) under N2 atmosphere at room temperature. The mixture was
stirred for 3 h and quenched with aqueous Na2S2O3 (1.0 M, 50 mL),
and the solution was extracted with CH2Cl2 (100 mL × 3). The
combined organic extracts were dried over Na2SO4 and concentrated
under vacuum to give the crude product. Purification by flash column
chromatography on silica gel (eluent: hexane−EtOAc, 9:1) gave 2ii in
93% yield (1.51 g).
Procedure for the Synthesis of 4aa and 4cc (Scheme 4a and b).
To a mixture of aromatic amine (0.5 mmol) and NaI (1.0 mmol, 150.0
mg) in an appropriate solvent (3 mL) was added t-BuOCl (1.0 mmol,
108.6 mg) under N2 atmosphere at the appropriate temperature. The
mixture was stirred for the indicated time and quenched with aqueous
Na2S2O3 (1.0 M, 10 mL), and the solution was extracted with CH2Cl2
(20 mL × 3). The combined organic extracts were dried over Na2SO4
and concentrated under vacuum to give the crude product. Purification
by flash column chromatography on silica gel (eluent: ethyl acetate in
hexane) gave homodimerized product.
Procedure for the Synthesis of 4bb (Scheme 4a). To a mix-
ture of 4aa (0.24 mmol, 98.9 mg), acetamide (1.44 mmol, 85.1 mg),
cesium carbonate (0.84 mmol, 272.7 mg), and 4,5-bis(diphenylphosphino)-
9,9-dimethylxanthene (Xantphos) (0.012 mmol, 11.0 mg) in dioxane
(2 mL) was added Pd2(dba)3 under argon atmosphere at room
temperature. The mixture was heated at 90 °C and stirred for 1 h.
The mixture was diluted with EtOAc (20 mL) and wash with brine.
The organic extracts were dried over Na2SO4 and concentrated under
vacuum to give the crude product. The crude product was washed with
CHCl3 to give 4bb.
(E)-1-(4-Acetylphenyl)-2-(3,5-bis(trifluoromethyl)phenyl)-
diazene (2js). Purified by silica gel column chromatography (hexane/
EtOAc 99:1 to 7:3); red solid (56.5 mg, 63%); mp 82.6−83.4 °C; Rf
1
0.25 (hexane/EtOAc 9:1); H NMR (270 MHz, CDCl3) δ 2.70 (s,
3H), 8.02 (s, 1H), 8.05 (d, 2H, J = 8.6 Hz), 8.15 (d, 2H, J = 8.6 Hz),
8.41 (s, 2H); 13C NMR (68 MHz, CDCl3) δ 26.9, 123.0 (q, J = 273.5
Hz), 123.2 (q, J = 3.4 Hz), 123.4, 124.4 (m), 129.5, 132.8 (q, J = 34.1
Hz), 139.4, 152.6, 154.2, 197.2; IR (ATR) ν 1694, 1369, 1358, 1277,
1258, 1206, 1163, 1126, 1103, 961, 903, 843 cm−1; MS (EI) m/z
(relative intensity, %) 360 ([M]+, 52), 119 ([C6H4COMe]+, 100),
147 ([N2C6H4COMe]+, 16), 213 ([C6H3(CF3)2]+, 42), 241
([N2C6H3(CF3)2]+, 2); HRMS (EI) m/z calcd for C16H10F6N2O
(M) 360.0697, found 360.0698.
(E)-Ethyl 4-((4-Nitrophenyl)diazenyl)benzoate (2il). Purified
by silica gel column chromatography (hexane/EtOAc 99:1 to 7:3); red
solid (49.3 mg, 66%); mp 159.7−160.9 °C; Rf 0.23 (hexane/EtOAc
9:1); 1H NMR (270 MHz, CDCl3) δ 1.44 (t, 3H. J = 7.0 Hz), 4.43 (q,
2H, J = 7.0 Hz), 7.97 (d, 2H, J = 8.9 Hz), 8.05 (d, 2H, J = 8.6 Hz),
8.21 (d, 2H, J = 8.6 Hz), 8.39 (d, 2H, J = 8.9 Hz); 13C NMR (68 MHz,
CDCl3) δ 14.4, 61.4, 123.0, 123.6, 124.6, 130.5, 133.3, 148.9, 154.4,
155.2, 165.5; IR (ATR) ν 1707, 1522, 1343, 1271, 1103, 862, 773 cm−1;
MS (EI) m/z (relative intensity, %) 299 ([M]+, 54), 122 ([C6H4NO2]+,
33), 149 ([C6H4CO2Et]+, 100), 177 ([N2C6H4CO2Et]+, 18); HRMS
(EI) m/z calcd for C15H13N3O4 (M) 299.0906, found 299.0904.
(E)-5-Methyl-3-(p-tolyldiazenyl)isoxazole (2bv). Purified by
silica gel column chromatography (hexane/EtOAc 99:1 to 8:2);
yellow solid (29.2 mg, 58%); mp 97.3−98.0 °C; Rf 0.30 (hexane/
1
EtOAc 9:1); H NMR (400 MHz, CDCl3) δ 2.45 (s, 3H), 2.50 (s,
3H), 6.37 (s, 1H), 7.33 (d, 2H, J = 8.0 Hz), 7.89 (d, 2H, J = 8.0 Hz);
13C NMR (100 MHz, CDCl3) δ 12.8, 21.6, 92.2, 123.6, 129.9, 143.7,
150.5, 171.0, 173.8; IR (ATR) ν 2926, 1726, 1602, 1470, 1153, 927,
823, 799 cm−1; MS (EI) m/z (relative intensity, %) 201 ([M]+, 26), 91
([C6H4CH3]+, 100), 119 ([N2C6H4CH3]+, 13); HRMS (EI) m/z calcd
for C11H11N3O (M) 201.0902, found 201.0900.
(E)-2-(4′-Tolylazo)-1-methylbenzimidazole (2bw). Purified by
silica gel column chromatography (hexane/EtOAc 99:1 to 7:3); orange
solid (38.3 mg, 61%); mp 175.4−176.0 °C; Rf 0.18 (hexane/EtOAc
7:3); 1H NMR (400 MHz, CDCl3) δ 2.47 (s, 3H), 4.21 (s, 3H), 7.35−
7.42 (m, 4H), 7.49 (d, 1H, J = 7.2 Hz), 7.91 (d, 1H, J = 7.2 Hz), 8.04
(d, 2H, J = 8.8 Hz); 13C NMR (100 MHz, CDCl3) δ 21.6, 29.6, 109.8,
121.7, 123.7, 123.8, 124.1, 129.8, 135.9, 141.9, 143.7, 151.3, 155.0; IR
(ATR) ν 1600, 1481, 1331, 1148, 817, 734 cm−1; MS (EI) m/z (relative
intensity, %) 250 ([M]+, 4), 91 ([C6H4CH3]+, 34), 201 (100); HRMS
(EI) m/z calcd for C15H14N4 (M) 250.1218, found 250.1217.
(E)-2-(4′-Bromophenylazo)-1-methylbenzimidazole (2gw).
Purified by silica gel column chromatography (hexane/EtOAc 99:1
to 7:3); orange solid (45.8 mg, 58%); mp 205.8−206.2 °C; Rf 0.20
1
(hexane/EtOAc 7:3); H NMR (400 MHz, CDCl3) δ 4.22 (s, 3H),
7.37−7.53 (m, 3H), 7.71 (d, 2H, J = 8.8 Hz), 7.92 (d, 1H, J = 7.2 Hz),
8.01 (d, 2H, J = 8.8 Hz); 13C NMR (100 MHz, CDCl3) δ 29.8, 110.0,
122.0, 124.2, 124.7, 125.0, 127.5, 132.5, 136.1, 142.1, 151.8, 154.8; IR
(ATR) ν 1491, 1329, 1146, 1063, 849, 816, 734 cm−1; MS (EI) m/z
(relative intensity, %) 314 ([M]+, 5), 287 (100); HRMS (EI) m/z
calcd for C14H11BrN4 (M) 314.0167, found 314.0168.
(E)-2-(4′-Acetylphenylazo)-1-methylbenzimidazole (2jw). Puri-
fied by silica gel column chromatography (CH2Cl2/EtOAc 99:1 to
9:1); red solid (39.2 mg, 56%); mp 228.1−228.8 °C; Rf 0.22 (CH2Cl2/
1
EtOAc 9:1); H NMR (400 MHz, CDCl3) δ 2.66 (s, 3H), 4.19 (s,
3H), 7.37−7.48 (m, 3H), 7.49 (d, 1H, J = 8.0 Hz), 8.11 (d, 1H, J = 8.8 Hz),
N
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Article
(E)-2,2′,6,6′-Tetrafluoro-4,4′-dibromoazobenzene (4aa).
Spectroscopic data were in agreement with those previously
reported.22b Purified by silica gel column chromatography (hexane/
EtOAc 95:5); red solid (63.9 mg, 62%); mp 169.5−170.4 °C; Rf 0.48
(hexane/EtOAc 9:1); 1H NMR (400 MHz, CDCl3) δ 7.29 (d, 4H, J =
1.2 Hz); IR (ATR) ν 3103, 3084, 1599, 1568, 1420, 1296, 1198, 1051,
874, 862, 839 cm−1; MS (EI) m/z (relative intensity, %) 412 ([M]+,
46), 112 (100), 191 ([C6H2BrF2]+, 70); HRMS (EI) m/z calcd for
C12H4Br2F4N2 (M) 409.8677, found 409.8680.
(E)-2,2′,6,6′-Tetrafluoro-4,4′-diacetoazobenzene (4bb). Spec-
troscopic data were in agreement with those previously reported.22b
red solid (72.8 mg, 82%); mp 362.8−364.0 °C; Rf 0.08 (hexane/
EtOAc 7:3); 1H NMR (400 MHz, d6-DMSO) δ 2.11 (s, 6H), 7.48 (d,
4H, J = 12.0 Hz), 10.63 (s, br, 2H); IR (ATR) ν 3302, 3271, 3121,
1678, 1599, 1539, 1420, 1371, 1348, 1265, 1150, 1053, 993, 841 cm−1;
MS (EI) m/z (relative intensity, %) 368 ([M]+, 98), 170
([C8H6F2NO]+, 100), 198 ([N2C8H6F2NO]+, 65); HRMS (EI) m/z
calcd for C16H12F4N4O2 (M) 368.0896, found 368.0895.
(E)-Diethyl-4,4′-(2,2′,6,6′-tetrafluoro)azobenzene Dicarboxylate
(4cc). Spectroscopic data were in agreement with those previously
reported.22b Purified by silica gel column chromatography (hexane/
EtOAc 9:1); red solid (81.7 mg, 82%); mp 145.8−146.0 °C; Rf 0.25
(hexane/EtOAc 9:1); 1H NMR (400 MHz, CDCl3) δ 1.43 (t, 6H, J =
6.8 Hz), 4.43 (q, 4H, J = 6.8 Hz), 7.75 (dd, 4H, J = 1.6, 10.4 Hz); IR
(ATR) ν 3375, 3098, 2978, 1721, 1574, 1435, 1330, 1236, 1053, 1018,
887, 767 cm−1; MS (EI) m/z (relative intensity, %) 398 ([M]+, 47),
213 ([N2C9H7F2O2]+, 100); HRMS (EI) m/z calcd for C18H14F4N2O4
(M) 398.0890, found 398.0891.
Procedure for pH Measurement. To a mixture of p-toluidine
(0.5 mmol, 53.6 mg) and NaI (1.0 mmol, 150.0 mg) in diethyl ether
(3 mL) was added t-BuOCl (1.0 mmol, 108.6 mg) under N2
atmosphere at room temperature. The mixture was stirred for 1 h,
and the resulting solution was extracted with water (10 mL). The pH
measurement of the water layer indicated 4.75.
This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Authors
*E-mail: takeda@chem.eng.osaka-u.ac.jp.
*E-mail: minakata@chem.eng.osaka-u.ac.jp.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This research was partly supported by a research Grant from
the Murata Science Foundation (to Y.T.), by a Grant-in-Aid for
Scientific Research (B) from the JSPS, Japan (No. 25288047, to
S.M.), and by a research Grant from the Nagase Science and
Technology Foundation (to S.M.). Also, Y.T. acknowledges all
support from the Frontier Research Base for Global Young
Researchers, Osaka University, from the Program of MEXT.
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Procedure for the Base Addition Experiment (Table 6). To a
mixture of p-toluidine (0.5 mmol, 53.6 mg), NaI (0.5 mmol, 75.0 mg), and
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ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra of azo products, full NMR spectra of
monitoring experiments, and ESI-MS spectra of iodoaniline.
O
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