A two-step oxidative aromatic substitution of hydrogen as a convenient way to 2-nitrodiarylamines

Article abstract of DOI:10.1016/j.tet.2016.10.060

A method for the synthesis of differently substituted 2-nitrodiarylamines via nucleophilic substitution of hydrogen in nitroarenes is described. In the two-step procedure, the first step omits classical substitution of halogens in starting nitroarenes and occurs efficiently at the position ortho to the activating group. Subsequent oxidation of the 2-nitrosoanilines so formed is accomplished with a cheap and environmentally friendly reagent, sodium perborate, under mild conditions. In exceptional cases of the amine-substituted nitrosoanilines, more selective oxidant (IBX) is required.

Full text of DOI:10.1016/j.tet.2016.10.060

Tetrahedron 72 (2016) 8252e8260
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A two-step oxidative aromatic substitution of hydrogen as a
convenient way to 2-nitrodiarylamines
*
ꢀ
Zbigniew Wrobel , Cezary Gulko, Karolina Plichta, Andrzej Kwast
Institute of Organic Chemistry Polish Academy of Sciences, Kasprzaka 44, 01-224, Warsaw, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
A method for the synthesis of differently substituted 2-nitrodiarylamines via nucleophilic substitution of
hydrogen in nitroarenes is described. In the two-step procedure, the first step omits classical substitution
of halogens in starting nitroarenes and occurs efficiently at the position ortho to the activating group.
Subsequent oxidation of the 2-nitrosoanilines so formed is accomplished with a cheap and environ-
mentally friendly reagent, sodium perborate, under mild conditions. In exceptional cases of the amine-
substituted nitrosoanilines, more selective oxidant (IBX) is required.
Received 22 July 2016
Received in revised form
11 October 2016
Accepted 24 October 2016
Available online 27 October 2016
© 2016 Elsevier Ltd. All rights reserved.
Keywords:
Nitroarenes
Oxidation
Nitroso group
Arylamination
1. Introduction
decarboxylative substitution of COOH group10 and Smiles/
Chapman rearrangement11 leading to o-nitrodiarylamines were
2-Nitrodiarylamines play an important role in organic synthesis
as intermediates in numerous syntheses of a variety of polynitrogen
heterocyclic compounds. In addition, they are important in bio-
organic as well as material chemistry, and some of them have been
reported to exhibit biological activity themselves (Fig. 1). Even the
simplest 2-nitrodiphenylamine was found to be capable of some
inhibition of amyloid fibril formation.1 Diversely substituted de-
rivatives of general formula A act as fungicides,2 B exhibits anti-HIV
and cytotoxic activity3 and C shows inhibitory effect on AKR1C3
enzyme.4
Despite the above applications, the number of convenient
methods for the synthesis of these compounds is rather limited.
The most popular one is substitution of halogens (fluorine or
chlorine) with an appropriate arylamine according to the SNAr
scheme, carried out under basic conditions3,5 which can be
moderated by the use of microwave irradiation.5c Other good
leaving groups in that reaction, for instance NO2, are less common.6
Substitution of poorer nucleofuges such as Br, I or OSO2C4F9,7
usually required Pd-based catalysts in the Buchwald-Hartwig re-
action.8 Pd- or Cu catalyzed cross-coupling reactions were used also
for N-arylation of unsubstituted ortho-nitroanilines.9 Occasionally,
reported. The most common methods require starting nitroarenes
ortho substituted with halogens or other functional groups wasted
during the substitution process, the use of metal catalysts, and
often harsh reaction conditions. Reported environmentally ori-
ented methods apparently could not avoid all of those problems.5d
A valuable alternative for the SNAr substitution of halogens is
nucleophilic aromatic substitution of hydrogen that can be
accomplished by means of various routes.12 The most regarded, and
of broader application in synthesis are vicarious (VNS) and oxida-
tive (ONSH) nucleophilic substitution of hydrogen. Both VNS13 and
ONSH14 were used successfully for the amination of nitroarenes.
However, while substitution of hydrogen with an unsubstituted
amino group by both methods is rather easy and quite general as
regards the nitroarene, N-arylamination is much more restricted.
An oxidative process was found to be effective mainly for relatively
electron-poor, reactive nitroarenes such as nitropyridine, nitro-
naphthalene or 2,4-dinitrobezene derivatives.14 Intermolecular
oxidative arylamination of mononitrobenzene was reported but
only para hydrogen can be substituted that way.15 The same limi-
tation was found for the VNS arylamination of nitrobenzene de-
rivatives with N-arylsulfenamides.13a Low nucleophilicity of the
arylamine nucleophile and in certain cases steric hindrance, can be
responsible for preferred para addition to the aromatic ring.
Furthermore, the competing ortho addition often leads to some
undesired processes. One example is the well-known Wohl-Aue
* Corresponding author.
ꢀ
E-mail address: zbigniew.wrobel@icho.edu.pl (Z. Wrobel).
http://dx.doi.org/10.1016/j.tet.2016.10.060
0040-4020/© 2016 Elsevier Ltd. All rights reserved.

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Z. Wrobel et al. / Tetrahedron 72 (2016) 8252e8260
8253
-
-
NO2
O
-
-
-
-
H
N
+
+
O
O
O
O
O
O
H
H
N
N
N
NO2
NO2
H
H
NHAr
H
CO2H
NAr
NAr
N
N
base
-H+
CN
F3C
R1
R2
B-
-
Q
Q
Q
I
II
adduct σH
A
B
C
Q = EWG
Fig. 1. Biologically active derivatives of 2-nitrodiarylamine.
-
[OX]
- OH
-
condensation of nitroarenes with aniline anions furnishing phen-
azines.16 The crucial step of this process comprises substitution of
the ortho hydrogen atom with concurrent reduction of the nitro
group, hence, the formation of intermediate ortho-nitro-
sodiphenylamine which undergo fast cyclization to the condensed
system.16c
O
O
NO2
N
N
Q
NHAr
NHAr
NAr
H+
Q
Q
In the course of our studies on the nucleophilic substitution of
hydrogen in nitroarenes we found that when the anilide anion was
generated by t-BuOK in THF or DMF at low temperature and was
reacted with nitroarenes, the reaction provided N-aryl-2-
nitrosoanilines,17 compounds for the synthesis of which there
were no usable methods until that time.18 That is, by application of
properly selected conditions the Wohl-Aue condensation could be
halted after its first step, and the ortho-arylamination of the
nitroarenes was achieved, although at the expense of the nitro
group being reduced.
Scheme 1. Two possible routes of transformation of the
conditions.
sH-adducts under basic
cases, however, the nitroanilines 4 are the only isolable products
(entries 5e7). These observations appear to be in accord with the
proposed mechanism of the reaction,17b involving base-promoted
deprotonation of the s-adduct to create a dianionic form suscep-
tible for both intramolecular elimination of water and oxidation by
the starting nitroarene as an oxidant (Scheme 1).
Despite a broad scope of nitroarenes and arylamines which
successfully form N-aryl-2-nitrosoanilines,17,19 in several cases, the
reaction does not occur selectively. The main products are accom-
panied with some amount of the corresponding 2-
nitrodiarylamines, apparently formed in the competitive oxida-
tive substitution reaction. It seemed to be of interest to examine
this undesired process and to try to employ it for the practical
synthesis of 2-nitrodiarylamines by nucleophilic substitution of
hydrogen.
The electron-withdrawing substituents present in both re-
actants apparently favor the latter process. Scheme 1 shows how
the electron-withdrawing group Q conjugates with a lone pair of
the nitro group (mesomeric structure II) which hinders intra-
molecular elimination of OHꢀ. Consequently, formation of a nitroso
group is obstructed and there is a chance for the oxidative process.
In accord with such understanding is an observation that N-
methylaniline which lacks a suitable N-hydrogen atom is not sus-
ceptible to the intramolecular dehydration, and it reacted with
nitroarenes giving products of ONSH exclusively, in yields depen-
dent on the excess of the nitroarene used.17b Poor nucleophilicity of
the arylamine anion (e.g. 4-cyanoaniline) is, supposedly, respon-
2. Results and discussion
sible for the unfavorable equilibrium constant of the
s
H-adduct
Under the standard, anaerobic reaction conditions used for the
formation of N-aryl-2-nitrosoanilines the spontaneous oxidative
process appeared to be rather exceptional, and restricted to the
relatively electron-poor reactants collected in Table 1. In certain
formation, and consequently, for the relatively high concentration
of the unbound starting nitroarene playing the role of an oxidant. In
both cases, the use of larger excess of the nitroarene favors the
Table 1
The SHNAr reactions of electron-poor nitroarenes and anilines.
-
-
O
O
O
O +
O
NO2
N
NH2
N
N
H
H
N
H
N
t-BuOK DMF
-65 oC -> T2
N
+
+
H
R1
R2
R1
R2
R2
R1
R2
R1
1
2
3
4
Entry
R1a
R2a
T2
3, Yield,b
%
4, Yield,b
%
1
2
3
4
5
6
7
4-Cl
4-Cl
2-Br-4-Cl
4-CF3
4-CF3
4-CN
4-CN
2-CN
2-Br-4-Cl
4-Cl
4-CN
4-CN
4-Cl
ꢀ65 ꢁC
r.t.
3a
3b
3c
3d
3e
3f
52 (27)c
4a
4b
4c
4d
4e
4f
8 (31)c
20
41
22
56
40
29
18
e
ꢀ65 ꢁC
ꢀ65 ꢁC
r.t.
r.t.
ꢀ65 ꢁC
e
60
40
4-CN
3g
e
4g
a
Numbering refers to the positions in the starting nitroarene and aniline.
Isolated yields.
In parentheses shown the yields of the reaction with 2 equiv. of 1.
b
c

ꢀ
8254
Z. Wrobel et al. / Tetrahedron 72 (2016) 8252e8260
O
N
O
O
NO2
NH2
N
H
H
N
N
base
oxidant
+
R1
R2
SNHAr
R1
R2
R2
R1
1
2
3
4
Scheme 2. Two-step synthesis of o-nitrodiarylamines via nucleophilic substitution of hydrogen.
oxidation and the yields of the corresponding nitroanilines 4 are
significantly higher (Table 1, entry 1).
Searching for a more general and efficient oxidation method,
applicable for 2-nitrosoanilines, several experiments with the
model nitrosoaniline 3h were performed (Table 2).
In order to direct the reaction of less electrophilic nitroarenes
towards the oxidative process, several modifications of the reaction
conditions were attempted, such as addition of external oxidants,
changes of the solvent and temperature of the reaction. They were
not successful, however, resulting in the formation of complex
mixtures of products of chemo- and regio-unselective processes.20
Since the main goal was to develop a simple, economical and
environmental friendly protocol for the synthesis of 2-
nitrodiarylamines from simple nitroarenes, we turned towards a
two-step approach which comprises substitution of ortho hydrogen
in nitroarenes with arylamines furnishing N-aryl-2-nitrosoanilines,
followed by subsequent oxidation of the latter (Scheme 2).
Oxidation of aromatic nitroso compounds to nitro compounds, a
process known for over a century, can be achieved by several
oxidizing agents which have been reviewed.21 In fact, the reaction
is of limited value in the synthesis of nitroaromatic compounds,
because the latter are generally more readily available. It should be
mentioned, however, that nitrosation of electron-rich aromatic
rings followed by oxidation of the intermediate nitroso compounds
Although a number of oxidizing systems gave reasonable yields
of 4a, we selected the relatively cheap and environmental friendly
sodium perborate tetrahydrate which in subsequent experiments
was found to be a convenient and efficient oxidant for a broad set of
2-nitrosoanilines 3 (Table 3). Sodium perborate is known as a ver-
satile reagent usable for oxidation of different functional groups
such as amines, sulfides, ketones, hydroquinones, but only one
example of the oxidation of nitrosobenzene to nitrobenzene has
been reported.29 In the case of N-aryl-2-nitrosoanilines, possessing
both reactive function, i.e. nitroso group and arylamino substituent,
the oxidant was found to be selective enough, so that the amine
nitrogen remained unaffected and the desired N-aryl-2-
nitroanilines were obtained in high yields.
The reaction gave satisfactory results for nitrosoanilines 3
variously substituted with moderate electron-withdrawing and
electron-donating groups in both aromatic rings, and was tolerant
towards sensitive bromides and iodides. However, poor results
were obtained in the oxidation of N-aryl-2-nitrosoanilines bearing
additional 5-alkylamino or 5-dialkylamino groups in the nitro-
soaromatic ring. The reactions produced multi-component mix-
tures, apparently as a result of unselective oxidation, involving not
only a nitroso group, but also the alkylamino substituent. For such
special type of nitrosoanilines a more selective oxidant was
required. After some research, positive results were obtained with
2-iodoxybenzoic acid (IBX), the oxidant rather ineffective in the
attempted oxidation of the model nitrosoaniline (Table 1). The
oxidation of appropriate N-aryl-2-nitrosoanilines 5a-f with IBX
23
with nitrous acid,22 K3Fe(CN)6 was applied, instead of non-
selective or low-yielding direct nitration, for the synthesis of
some nitroarenes. For this aim to be achieved, catalytic oxidation by
26
H2O2 in the presence of nitric acid,24 CH3ReO3,25 CrO3
or
(NH4)6Mo7O2427 was also used successfully. A few examples of the
occasional oxidation of N-substituted 2-nitrosoanilines using
hydrogen peroxide under acidic18a or basic18b,c conditions as well as
by m-CPBA28 have been reported as a proof for the structure of the
corresponding nitroso compounds.
Table 2
Oxidation of nitrosoaniline 3h under various conditions.
-
O
+
O
O
N
H
N
H
N
N
conditions
Cl
Cl
3h
4h
Entry
Oxidant
Catalyst (mol %)
Solvent
Temperature
Time,a
h
Yield,b
%
1
2
3
4
5
6
7
8
9
H2O2
H2O2
H2O2
H2O2
NaOH (excess)
e
MeOH
AcOH
EtOH
MeOH
DCMc
AcOH
CH2Cl2
DMSO
DMSO
r.t.
r.t.
3
24
3
35
46
76
77
CrO3 (30)
(NH4)6Mo7O24$4H2O (30)
Na2WO4$2H2O (15)
e
60 ꢁC
60 ꢁC
r.t.
6
H2O2
48d
2
traces
99
74
no reaction
decomp.
Na2BO3$4H2O
m-CPBA
IBXe
40 ꢁC
r.t
e
-
0.1
24
4
r.t or 40 ꢁC
110 ꢁC
IBXe
e
a
Reactions carried out until apparent disappearance of 3h by tlc.
Yields based on quantitative GC analyses.
Vigorously stirred two-phase system.
No conversion of 3h was observed by tlc.
2-Iodoxybenzoic acid.
b
c
d
e

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Z. Wrobel et al. / Tetrahedron 72 (2016) 8252e8260
8255
Table 3
NO2
NO2
H
Oxidation of nitrosoanilines 3h-x with sodium perborate tetrahydrate.
H
N
N
-
O
O
O
+
Cl
N
N
H
N
H
N
O
N
N
Na2B2O8 4H2O / AcOH
R2
6a 69%
6b 69%
R2
R1
R1
3
4
NO2
NO2
H
N
H
N
Entry R1
R2
3
Temp. ꢁC Time, h
4
Yield %a
1
2
3
4
5
6
7
8
5-Cl
40-Me
40-Me
20,60-Me2
20-I
3h
3i
3j
3k
3l
3m 55
45
45
45
45
45
2
1
1.5
1.5
3
1
2
3
2
0.5
0.5
2
1.5
1.5
10
2
4h
4i
4j
4k
4l
4m 98
4n
4o
4p
4q
4r
4s
4t
4u
4v
4w
4x
92
64
85
98
90
Cl
5-F
5-F
5-Cl
5-OMe 40-Br
4-CF3
4-CF3
3,5-Cl2
5-Cl
H
HN
N
6c 76%
6d 86%
40-Cl
50-Cl-20-OMe 3n
55
85
45
45
45
45
45
45
45
45
45
98
56
95
84
50
74
86
96
69
75
95
40-Cl
3o
3p
3q
3r
3s
3t
3u
3v
3w
3x
NO2
NO2
H
N
H
9
40-Cl
N
10
11
12
13
14
15
16
17
40-OMe
20-F
5-Cl
H
5-Cl
20-Cl
Cl
Cl
20-t-Bu
HN
HN
5-OMe 20-t-Bu
5-Cl
5-OMe 40-Me
5-F
20-I-40-Me
6e 62%
6f 65%
40-Cl
4
Fig. 2. Nitroanilines 6a-f obtained by oxidation of corresponding 5-amino-2-
a
Isolated yield.
nitrosoanilines 5a-f.
nitrogen atom in the step of elimination of IBA (2-iodosobenzoic
acid), making the whole process much easier (Scheme 3).
(DMSO, room temperature, 20 h) gave nitroanilines 6a-f collected
in Fig. 2.
To our best knowledge, this versatile reagent30 has never been
used for oxidation of nitroso compounds, while the oxidation of
arylamine31 and anilide32 groups have been reported. Thus, the
selectivity of IBX in the oxidation of 5, having three different ni-
trogen groups, might be a serious concern. In both reports, how-
ever, it was stated that an arylamine moiety substituted with strong
EWG groups, such as nitro group, remained resistant towards this
oxidant. Extensive mechanistic investigations led to the conclusion
that several reactions of IBX, including oxidation of amines, are
initiated by single electron transfer (SET) from the substrate to IBX
to form a radical cation, a process which presumably is prevented
by strong EWG. It is reasonable to assume, that a nitroso group
should also prevent the undesired oxidation of the amine nitrogen
atoms in the starting 5-amino-2-nitrosoanilines, and in the same
way, the resulting nitro group prevents the product from under-
going undesired subsequent oxidation.
3. Conclusion
The developed two-step method for the synthesis of differently
substituted 2-nitrodiarylamines engages nucleophilic substitution
of hydrogen in nitroarenes followed by oxidation of the 2-
nitrosoanilines so formed, with a cheap and environmentally
friendly reagent. The first step omits classical substitution of hal-
ogens in the starting nitroarenes, occurs efficiently at the position
ortho to the activating group, and potential leaving groups para (F,
Cl, OR) or ortho (Cl, OR) to the nitro group remain unaffected. The
oxidation step, which can be carried out with the crude product
from the first step, occurs under mild conditions with sodium
perborate tetrahydrate and only in exceptional cases of the amine-
substituted compounds requires a special, more selective oxidant
(IBX). The above features make the method a valuable alternative to
the popular methods based on the SNAr reaction.
A nitroso group is often considered as an aza-analogue of a
carbonyl group of aldehydes, and indeed, it shows similar reactivity
and undergoes similar reactions, such as nucleophilic addition and
condensation, reduction and oxidation with most typical redox
reagents. In this respect, however, oxidation with IBX seems
different. This oxidant is known for efficient oxidation of a broad
range of alcohols to the corresponding carbonyl compounds, which
in the case of primary alcohols are aldehydes. Further oxidation of
aldehydes to carboxylic acids is very rare, however, and requires
special conditions such as the additional presence of hydroxylic
nucleophile33 or a solvent-free system at elevated temperature.34
Contrary to that, the nitroso group of nitrosoanilines 5a-f is
oxidized readily under very mild conditions (DMSO, ambient
temperature) and the yields are reasonable.
Ar
_
N
-
-
O
O
HO
OH
+
O
I
I
O
+
O
+
Ar
N
O
O
O
5
IBX
OH
O
O
O
I
+
Ar
N
+
-
O
6
A possible mechanism of the IBX oxidation of nitrosoarenes may
be analogous to the ionic mechanism proposed for the oxidation of
aldehydes,34 except that it involves a lone electron pair of the
IBA
Scheme 3. Proposed mechanistic scheme for the oxidation nitrosoanilines 5 with IBX.

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Z. Wrobel et al. / Tetrahedron 72 (2016) 8252e8260
8256
4. Experimental section
[MþNa]þ calcd for C12H6N2O35Cl729Br2Na: 444.8122; found:
444.8110.
4.1. General
4.3.4. N-(4-Chlorophenyl)-2-nitroso-5-trifluoromethylaniline (3d)
Dark solid; mp 84e85 ꢁC; 1H NMR (500 MHz, CDCl3):
1H and 13C NMR spectra were recorded on a Varian Mercury 500
instruments at 298 K. Chemical shifts are expressed in ppm referred
to TMS (1H NMR at 500 MHz,13C NMR at 125 MHz), coupling con-
stants in Hertz. Mass spectra (EI, 70 eV and ESI in MeOH) were
obtained on an AutoSpec Premier and an API 365 spectrometers. IR
spectra were recorded on a JASCO FT/IR-6200 apparatus. GC ana-
lyses were performed on a Hewlett Packard HP6890 GC system
with HP5 column and FID (carrier gas e helium). Silica gel Merck 60
(230e400 mesh) was used for column chromatography. THF was
distilled from sodium/benzophenone ketyl prior to use. DMF was
dried over CaH2, distilled and stored over molecular sieves.
d
¼ 7.18e7.28 (m, 3 H), 7.33 (s, 1 H), 7.4e7.56 (m, 2 H), 8.88 (d,
J ¼ 6.9 Hz, 1 H), 11.56 (br s, 1 H); 13C NMR (125 MHz, CDCl3):
d
¼ 113.3 (q, JCF ¼ 4.2 Hz), 114.1 (q, JCF ¼ 3.3 Hz), 122.9 (q,
JCF ¼ 274 Hz), 126.0, 130.2, 132.5, 134.9, 137.8 (q, JCF ¼ 32.7 Hz),
148.9, 155.7; MS (ESI, MeOH): m/z ¼ 301 [MþH]þ; HRMS (ESI): m/z
[MþH]þ calcd for C11H9N2O35ClF3: 301.1496; found: 301.1490.
4.3.5. 5-Chloro-N-(4-cyanophenyl)-2-nitroaniline (4a)
Orange needles; mp 234 ꢁC (lit.35 221e224 ꢁC); IR (KBr): 3322,
3114, 3097, 2225, 1599, 1563, 1502, 1483, 1336, 1251, 1066, 936, 836,
747, 552 cmꢀ1; 1H NMR (500 MHz, DMSO-d6):
d
¼ 7.16 (dd, J ¼ 2.0,
Following nitrosoanilines were obtained and described previ-
ously: 3h, 3p, 3w17a; 3i 34a; 3j, 3l, 3o, 3x 17b; 3k, 3v19c; 3m, 3n19d
;
8.9,1 H), 7.4 (d, J ¼ 8.9, 2 H), 7.78 (d, J ¼ 8.9, 2 H), 7.45 (d, J ¼ 2.2,1 H),
3q19e; 3r, 3s19f; 3t19g; 5b, c, f19h; 5e19b
.
8.14 (d, J ¼ 8.9, 1 H), 9.48 (s, 1H); 13C NMR (125 MHz, DMSO-d6):
d
¼ 104.5, 119.1, 119.2, 120.3, 121.1, 128.2, 133.7, 136.1, 139.1, 140.0,
144.8; MS (EI, 70 eV): m/z (%) 275 (41), 273 (Mþ, 100), 256 (15), 239
(38), 228 (27); HRMS (EI): m/z [M]þ calcd for C13H8N3O235Cl:
273.0305; found: 273.0304.
4.2. Reactions of electron-poor nitroarenes and anilines (Table 1)
To a cooled solution of t-BuOK (6 mmol, 672 mg) in DMF (12 mL)
was added dropwise at ꢀ65 ꢁC a solution of aniline 1 (2 mmol),
then nitroarene 2 (2 mmol) in DMF (2 mL each). The mixture was
stirred at this temperature for 20e60 min or, in a few cases, the
cooling bath was removed and the mixture was allowed to reach
room temperature (see Table 1). The reaction mixture was then
poured into a concentrated NH4Cl solution (ca. 50 mL) and
extracted with EtOAc. The extract was washed thoroughly with
water and brine, and dried with Na2SO4. After evaporation, the
crude product was subjected to column chromatography (SiO2,
hexane/AcOEt, hexane/CH2Cl2 or hexane/toluene) to isolate 3 and/
or 4.
4.3.6. 5-Chloro-N-(2-cyanophenyl)-2-nitroaniline (4b)
Orange crystals; mp 140e141 ꢁC; 1H NMR (500 MHz, CDCl3):
d
¼ 6.90 (dd, J ¼ 2.0, 9.1, 1 H); 7.14 (d, J ¼ 2.0 Hz, 1 H), 7.34 (dd,
J ¼ 8.2, 7.7 Hz, 1 H); 7.67 (ddd, J ¼ 8.2, 8.2, 1.4 Hz, 1 H); 7.75 (dd,
J ¼ 1.4, 7.7 Hz, 1 H), 7.51 (d, J ¼ 8.2 Hz, 1 H), 8.21 (d, J ¼ 9.1 Hz, 1 H),
9.67 (s, 1 H); 13C NMR (125 MHz, CDCl3):
d
¼ 108.4, 115.9, 116.0,
120.0, 123.9, 125.9, 128.2, 133.1, 134.1, 134.2; 141.4; 141.5; 142.4; MS
(EI, 70 eV): m/z (%) 273 (100), 241 (11), 239 (28), 228 (23), 192 (58);
HRMS (EI): m/z [M]þ calcd for C13H8N3O325Cl: 273.0305; found:
273.0302.
4.3. Characterization of N-aryl-2-nitrosoanilines 3a-d and
nitroanilines 4a-g (Table 1)
4.3.7. 3-Bromo-5-chloro-N-(2-bromo-4-chlorophenyl)-2-
nitroaniline (4c)
Yellow crystals; mp 167e168 ꢁC; 1H NMR (500 MHz, CDCl3):
4.3.1. 5-Chloro-N-(4-cyanophenyl)-2-nitrosoaniline (3a)
d
¼ 6.82 (dd, J ¼ 9.2, 2.1 Hz, 1 H), 6.99 (d, J ¼ 2.1 Hz, 1 H), 7.37e7.38
Red solid; mp 205e206 ꢁC; IR (KBr): 3296, 3095, 2921, 2224,
1594, 1552, 1507, 1458, 1336, 1264, 1157, 1107, 1078, 941, 818, 795,
(m, 2 H), 7.72e7.73 (m, 1 H), 8.18 (d, J ¼ 9.2 Hz, 1 H), 9.44 (s, 1 H); 13
C
567 cmꢀ1; 1H NMR (500 MHz, CDCl3):
d
¼ 7.09 (dd, J ¼ 2.0, 8.7 Hz,
NMR (125 MHz, CDCl3):
d
¼ 115.2, 119.0, 120.4, 126.0128.2, 128.8,
132.0, 132.4, 133.6, 135.6, 142.3, 142.5; MS (EI, 70 eV): m/z (%) ¼ 444
(4), 442 (11), 440 (13), 438 (Mþ 5), 364 (45), 362 (100), 360 (62);
HRMS (EI): m/z [M]þ calcd for C12H6N2O235Cl729Br2: 437.8173; found:
437.8175.
1 H), 7.31 (d, J ¼ 2.0 Hz, 1 H), 7.38e7.42 (m, 2 H), 7.71e7.74 (m, 2 H),
8.56 (br s, 1 H), 11.42 (br s, 1 H); 13C NMR (125 MHz, CDCl3):
d
¼ 108.9, 114.4, 118.3, 120.4, 123.3, 132.5, 133.9, 137.7, 141.7, 145.1,
155.1; MS (EI, 70 eV): m/z (%) 257 (Mþ, 22), 240 (100), 226 (46), 192
(47), 164 (19); HRMS (EI) m/z [M]þ calcd for C13H8N3O35Cl:
257.0356; found: 257.0356.
4.3.8. N-(4-Chlorophenyl)-2-nitro-5-trifluoromethylaniline (4d)
Orange crystals; mp 161 ꢁC; 1H NMR (500 MHz, CDCl3):
d
¼ 7.01
(dd, J ¼ 1.5, 8.8 Hz, 1 H), 7.21e7.25 (m, 2H), 7.38 (d, J ¼ 0.7 Hz, 1 H),
4.3.2. 5-Chloro-N-(2-cyanophenyl)-2-nitrosoaniline (3b)
7.42e7.45 (m, 2 H), 8.32 (d, J ¼ 8.8 Hz, 1 H), 9.45 (s, 1 H); 13C NMR
Dark solid; mp 128e129 ꢁC; 1H NMR (500 MHz, CDCl3):
(125 MHz, CDCl3):
d
¼ 113.2, (q, JCF ¼ 4.0 Hz), 113.8 (q, JCF ¼ 3.5 Hz),
d
¼ 7.02e7.12 (m, 2 H); 7.37 (ddd, J ¼ 1.2, 7.9, 9.1 Hz, 1 H); 7.56 (d,
122.7 (q, JCF ¼ 273 Hz), 125.9, 127.8, 130.3, 132.0, 134.6, 136.3, 137.0
(q, JCF ¼ 33.2 Hz), 142.6; MS (EI, 70 eV): m/z (%) ¼ 316 (100), 284
(10), 282 (25), 269 (41); HRMS (EI): m/z [M]þ calcd for
J ¼ 7.9 Hz, 1 H), 7.67 (ddd, J ¼ 1.2, 7.9, 9.1 Hz, 1 H); 7.75 (dd, J ¼ 1.2,
7.9 Hz, 1 H), 8.58 (br s, 1 H), 11.4 (br s, 1 H); 13C NMR (125 MHz,
CDCl3):
d
¼ 108.6,114.4, 115.9, 120.3,124.9, 126.4, 134.0, 134.1, 140.4;
C
13H8N2O325ClF3: 316.0226; found: 316.0236.
144.8; 155.0; MS (ESI, MeOH): m/z ¼ 258 [MþH]þ; HRMS (ESI): m/z
[MþH]þ calcd for C13H9N3O35Cl: 258.0434; found: 258.0426.
4.3.9. N-(4-Cyanophenyl)-2-nitro-5-trifluoromethylaniline (4e)
Yellow crystals; mp 93e94 ꢁC; 1H NMR (500 MHz, CDCl3):
4.3.3. 3-Bromo-5-chloro-N-(2-bromo-4-chlorophenyl)-2-
nitrosoaniline (3c)
d
¼ 7.18 (dd, J ¼ 1.7, 8.7 Hz, 1 H), 7.34e7.38 (m, 2 H), 7.65 (br s, 1 H),
Dark solid; mp 128e134 ꢁC; 1H NMR (500 MHz, DMSO-d6):
7.71e7.75 (m, 2 H), 8.35 (d, J ¼ 8.7 Hz, 1 H), 9.50 (br s, 1 H); 13C NMR
d
¼ 6.79 (d, J ¼ 2.0 Hz, 1 H), 7.30 (d, J ¼ 8.4 Hz, 1 H), 7.36e7.41 (m,
(125 MHz, CDCl3):
d
¼ 108.4, 114.2 (q, JCF ¼ 4.0 Hz), 115.9 (q,
2 H), 7.72 (d, J ¼ 2.0 Hz, 1 H), 12.28 (br s, 1 H); 13C NMR (125 MHz,
JCF ¼ 3.5 Hz), 118.3, 122.0, 122.6 (q, JCF ¼ 273 Hz), 128.0, 134.1, 136.5,
137.0 (q, JCF ¼ 33 Hz), 140.0, 142.6; MS (EI, 70 eV): m/z (%) ¼ 307
(45), 273 (100), 260 (21), 240 (2); HRMS (EI): m/z [M]þ calcd for
CDCl3):
d
¼ 114.4, 120.7, 123.7, 127.8, 128.3, 128.9, 132.3, 133.6,
133.66, 133.71, 138.5, 144.8, 151.2; MS (EI, 70 eV): m/z (%) ¼ 426 (4),
424 (6), 422 (Mþ 4), 347 (56), 345 (100), 343 (73); HRMS (ESI) m/z
C14H8N3O2F3: 307.0569; found: 307.0576.

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4.3.10. 5-Cyano-N-(4-cyanophenyl)-2-nitroaniline (4f)
Orange solid; mp 139e140 ꢁC; IR (KBr): 3297, 3111, 2224, 1600,
1584, 1564, 1504, 1483, 1338, 1254, 1064, 842, 663 cmꢀ1 1H NMR
(500 MHz, DMSO-d6):
281.1533.
;
4.6.2. 5-n-Butylamino-N-(4-methylphenyl)-2-nitrosoaniline (5d)
d
¼ 7.36e7.40 (m, 2H), 7.53 (dd, J ¼ 1.5,
Yield 97%; Dark reddish solid; mp 112e114 ꢁC; 1H NMR
8.5 Hz, 1 H), 7.75e7.79 (m, 2 H), 7.94 (d, J ¼ 1.5 Hz, 1 H), 8.22 (d,
(500 MHz, CDCl3):
d
¼ 0.92 (t, J ¼ 7.4 Hz, 3 H), 1.34e1.42 (m, 2 H),
J ¼ 8.5 Hz, 1 H), 9.45 (s, 1 H); 13C NMR (125 MHz, DMSO-d6):
1.56e1.63 (m, 2 H),2.35 (s, 3 H), 3.10e3.16 (m, 2 H), 5.35 (br s, 1 H),
5.91 (d, J ¼ 2.2 Hz, 1 H), 6.27 (dd, J ¼ 9.2, 1.5 Hz, 1 H), 7.14e7.20 (m,
4 H), 8.02 (d, J ¼ 9.2 Hz, 1 H), 13.42 (br s, 1 H); 13C NMR (125 MHz,
d
¼ 104.7, 117.6, 117.7, 119.6, 120.2, 124.5, 125.6, 127.8, 134.2, 138.1,
140.8, 145.5; MS (EI, 70 eV): m/z (%) ¼ 264 (100), 247 (14), 230 (22),
219 (17); HRMS (EI): m/z [M]þ calcd for C14H8N4O2: 264.0647;
found: 264.0644.
CDCl3):
d
¼ 13.7, 20.1, 21.0, 31.0, 42.9, 87.6, 109.7, 124.6, 130.0, 135.0,
135.6, 140.8, 141.4, 152.0, 155.5; MS(EI): m/z (%) 283 (Mþ, 56), 266
(100), 226 (58), 209 (54); HRMS(EI): m/z [M]þ calcd for C17H21N3O:
283.1685; found: 283.1685.
4.3.11. N-(4-Chlorophenyl)-5-cyano-2-nitroaniline (4g)
Orange solid; mp 133 ꢁC; 1H NMR (500 MHz, CDCl3):
d
¼ 7.01
(dd, J ¼ 1.5, 8.5 Hz, 1 H), 7.18e7.24 (m, 2 H), 7.38 (d, J ¼ 1.5 Hz, 1 H),
4.7. Oxidation of N-aryl-2-nitrosoanilines 3 with sodium perborate.
Synthesis of 2-nitrodiarylamines 4 (Table 3); general procedure
7.42e7.5 (m, 2 H), 8.30 (d, J ¼ 8.5 Hz, 1 H), 9.41 (br s, 1 H); 13C NMR
(125 MHz, CDCl3):
d
¼ 117.0, 119.1, 119.5, 120.3, 126.3, 127.8, 130.5,
132.6, 134.8, 135.8, 142.8; MS (EI, 70 eV): m/z (%) ¼ 253 (58), 237
To a solution of nitrosoaniline 3 (1.0 mmol) in AcOH (8 mL) was
added NaBO3$4H2O (460 g, 3.0 mmol) and the mixture was stirred
at the temperature and for the time specified in Table 1. The reac-
tion mixture was then poured into water (ca. 100 mL) and extracted
with EtOAc (3 ꢂ 30 mL). The combined extract was washed with
water (3 ꢂ 100 mL), brine, and dried with Na2SO4. After evaporation
the crude product was purified by column chromatography (SiO2,
hexane/EtOAc).
(26), 236 (100), 222 (40); HRMS (EI): m/z [M]þ calcd for
C
14H11N3O2: 253.0851; found: 253.0855.
4.4. Preparation of nitrosoaniline 3u
To a cooled solution of t-BuOK (6 mmol, 672 mg) in DMF (12 mL)
was added dropwise at ꢀ65 ꢁC a solution of 2-t-butylaniline
(298 mg, 2 mmol), then p-nitroaanisole (274 mg, 2 mmol) in DMF
(2 mL each). The mixture was stirred at this temperature for 60 min.
The reaction mixture was then poured into a concentrated NH4Cl
solution (ca. 50 mL) and extracted with EtOAc. The extract was
washed thoroughly with water and brine, and dried with Na2SO4.
After evaporation, the crude product was subjected to column
chromatography (SiO2, hexane/toluene) to isolate 3u, 432 mg (76%
yield).
4.8. Characterization of 2-nitrodiarylamines 4 (Table 3)
4.8.1. 5-Chloro-2-nitro-N-(4-methylphenyl)-aniline (4h)
Red solid; mp 126e127 ꢁC (lit36 125e126 ꢁC); IR (KBr): 3332,
3112, 3032, 2919, 1605, 1565, 1511, 1483, 1336, 1246, 931, 784,
529 cmꢀ1
;
1H NMR (500 MHz, CDCl3):
d
¼ 2.39 (s, 3 H), 6.68 (dd,
J ¼ 9.2, 2.1 Hz, 1 H), 7.07 (d, J ¼ 2.1 Hz, 1 H), 7.14e7.17 (m, 2 H),
7.24e7.27 (m, 2 H), 8.14 (d, J ¼ 9.2 Hz, 1 H), 9.49 (broad s, 1 H); 13
C
4.4.1. N-(2-t-Butylphenyl)-5-methoxy-2-nitrosoaniline (3u)
Dark green crystals; mp 75e76 ꢁC; 1H NMR (500 MHz, CDCl3):
NMR (125 MHz, CDCl3):
d
¼ 21.04, 115.10, 117.52, 125.17, 128.06,
130.56, 131.20, 135.08, 136.55, 142.46, 144.47; MS(EI): m/z (%) 262
(Mþ,100), 228 (44), 215 (39),180 (37),181 (36); HRMS(EI): m/z [M]þ
calcd for C13H11N2O325Cl: 262.0509; found: 262.0507.
d
¼ 1.37 (s, 9 H), 3.71 (s, 3 H), 5.97 (d, J ¼ 2.2 Hz, 1 H), 6.55 (dd,
J ¼ 9.2, 2.2 Hz, 1 H), 7.18e7.30 (m, 3 H), 7.52 (dd, J ¼ 7.8, 1.0 Hz, 1 H),
8.52 (d, J ¼ 9.2 Hz, 1 H), 13.2 (s, 1 H); 13C NMR (125 MHz, CDCl3):
d
¼ 30.6, 35.0, 55.8, 94.2, 109.2, 127.0, 127.5, 127.7, 129.3,135.1, 139.0,
4.8.2. 5-Fluoro-2-nitro-N-(4-methylphenyl)-aniline (4i)
142.3, 146.3, 154.0, 167.0; MS (ESI): m/z [MþH]þ ¼ 285; HRMS (ESI):
Orange crystals; mp 125e128 ꢁC; 1H NMR (500 MHz, CDCl3):
m/z [MþH]þ calcd for C17H21N2O2: 285.1603; found: 285.1605.
d
¼ 2.39 (s, 3 H), 6.44 (ddd, J ¼ 9.5, 2.6 Hz, JHF ¼ 7.1 Hz,1 H), 6.72 (dd,
J ¼ 2.6 Hz, JHF ¼ 11.5 Hz, 1 H), 7.14e7.17 (m, 2 H), 7.23e7.27 (m, 2 H),
4.5. Preparation of nitrosoanilines 5a and 5d. General procedure19h
8.24 (dd, J ¼ 9.5 Hz, JHF ¼ 6.12 Hz, 1 H), 9.58 (br s, 1 H); 13C NMR
(125 MHz, CDCl3):
d
¼ 21.0, 101.2 (d, JCF ¼ 27.6 Hz), 105.6 (d,
To a solution of 5-fluoro-N-(4-methylphenyl)-2-nitrosoaniline
3i (0.5 mmol) in MeCN (10 mL) was added appropriate amine
(2.5 mmol) and the mixture was stirred at ambient temperature for
1 h. After the reaction was complete the mixture was poured into
water and extracted three times with AcOEt. The combined extracts
were washed with water, brine and the solvent was evaporated.
The crude product was pure enough to use in the oxidation
reaction.
JCF ¼ 24.6 Hz), 125.2, 129.5, 129.7 (d, JCF ¼ 12.0 Hz), 130.5, 135.2,
136.6, 146.1 (d, JCF ¼ 13.3 Hz), 167.2 (d, JCF ¼ 254.6 Hz); MS(EI): m/z
(%) 246 (Mþ, 100), 212 (40), 198 (46), 185 (31); HRMS(EI): m/z [M]þ
calcd for C13H11N2O2F: 246.0805; found: 246.0809.
4.8.3. 5-Fluoro-N-(2,6-dimethylphenyl)-2-nitroaniline (4j)
Yellow crystals; mp 90e91 ꢁC; 1H NMR (500 MHz, CDCl3):
d
¼ 2.20 (s, 3 H), 6.00 (dd, J ¼ 2.6 Hz, JHF ¼ 11.3 Hz, 1 H), 6.42 (ddd,
J ¼ 9.6, 2.6 Hz, JHF ¼ 7.1 Hz, 1 H), 7.17e7.24 (m, 3 H), 8.27 (dd,
4.6. Characterization of new N-aryl-2-nitrosoanilines 5
J ¼ 9.6 Hz, JHF ¼ 6.1 Hz, 1 H), 9.28 (br s, 1 H); 13C NMR (125 MHz,
CDCl3):
d
¼ 18.1, 100.3 (d, JCF ¼ 27.6 Hz), 105.2 (d, JCF ¼ 24.8 Hz),
4.6.1. N-(4-Methylphenyl)-2-nitroso-5-(pyrrolidin-1-yl)aniline
(5a)
128.1, 128.9, 129.8 (d, JCF ¼ 12.0 Hz), 134.8, 136.5, 146.7 (d,
JCF ¼ 13.3 Hz), 167.7 (d, JCF ¼ 254.6 Hz), one signal missing; MS(EI):
m/z (%) 260 (Mþ, 100), 212 (68), 198 (38); HRMS(EI): m/z [M]þ calcd
for C14H13N2O2F: 260.0961; found: 260.0971.
Yield 95%; Dark green solid; mp 161e164 ꢁC; IR (KBr): 2966,
2867, 1625, 1496, 1314, 1136, 911, 804, 663, 503 cmꢀ1 1H NMR
;
(500 MHz, CDCl3):
d
¼ 1.98e2.03 (m, 4 H), 2.35 (s, 3 H), 3.2e3.6 (m,
4 H), 5.87 (d, J ¼ 2.4 Hz, 1 H), 6.35 (dd, J ¼ 9.5, 2.4 Hz, 1 H), 8.10 (d,
4.8.4. 5-Chloro-N-(2-iodophenyl)-2-nitroaniline (4k)
J ¼ 9.5 Hz, 1 H), 13.12 (s, 1 H); 13C NMR (125 MHz, CDCl3):
d
¼ 21.0,
Orange crystals; mp 130e132 ꢁC; 1H NMR (500 MHz, CDCl3):
25.2, 48.2, 89.1, 107.6, 124.4, 130.0, 135.2, 135.3, 139.8, 141.8, 151.9,
153.4; MS(EI): m/z (%) 281 (Mþ, 67), 267 (83), 264 (100), 250 (42);
HRMS(EI): m/z [M]þ calcd for C17H19N3O: 281.1528; found:
d
¼ 6.78 (dd, J ¼ 9.2, 2.2 Hz, 1 H), 6.93 (d, J ¼ 2.2 Hz, 1 H), 7.00e7.05
(m, 1 H), 7.41 (dd, J ¼ 8.0, 1.5 Hz, 1 H), 7.42e7.46 (m, 1 H), 7.97 (dd,
J ¼ 8.0, 1.2 Hz, 1 H), 8.19 (d, J ¼ 9.2 Hz, 1 H), 9.46 (br s, 1 H); 13C NMR

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8258
(125 MHz, CDCl3):
d
¼ 96.9, 115.2, 118.5, 125.8, 128.1, 128.1, 129.6,
154 (44); HRMS(EI): m/z [M]þ calcd for C13H12N2O3: 244.0848;
found: 244.0847.
131.9, 139.9, 140.4, 142.5, 143.0; MS(EI): m/z (%) 376 (41), 374 (Mþ,
100), 230 (44), 202 (50), 201 (54), 166 (54); HRMS(EI): m/z [M]þ
calcd for C12H8N2O2I: 373.9319; found: 373.9329.
4.8.11. 5-Chloro-N-(2-fluorophenyl)-2-nitroaniline (4r)
Yellow crystals; mp 138e140 ꢁC; 1H NMR (500 MHz, CDCl3):
4.8.5. N-(4-Bromophenyl)-5-methoxy-2-nitroaniline (4l)
d
¼ 6.78 (dd, J ¼ 9.1, 2.2 Hz, 1 H), 6.97e6.99 (m, 1 H), 7.21e7.32 (m,
3 H), 7.36e7.41 (m, 1 H), 8.17 (d, J ¼ 9.1 Hz, 1 H), 9.35 (broad s, 1 H);
13C NMR (125 MHz, CDCl3):
Orange crystals; mp 147e150 ꢁC (lit.37 149 ꢁC); 1H NMR
(500 MHz, CDCl3):
d
¼ 3.76 (s, 3 H), 6.37 (dd, J ¼ 9.5, 2.6 Hz, 1 H),
d
¼ 15.2, 117.0 (d, JCF ¼ 19.5 Hz), 118.4,
6.52 (d, J ¼ 2.6 Hz, 1 H), 7.16e7.20 (m, 2 H), 7.52e7.56 (m, 2 H), 8.19
125.0 (d, JCF ¼ 4.0 Hz), 125.7 (JCF ¼ 12.0 Hz), 127.3 (d, JCF ¼ 7.4 Hz),
128.0, 132.0, 142.5, 143.2, 156.9 (d, JCF ¼ 247.8 Hz), one signal
missing; MS(EI): m/z (%) 268 (46), 266 (Mþ, 100), 232 (45), 219 (49),
185 (46); HRMS(EI): m/z [M]þ calcd for C12H8N2O235ClF: 266.0258;
found: 266.0261.
(d, J ¼ 9.5 Hz, 1 H), 9.66 (broad s, 1 H); 13C NMR (125 MHz, CDCl3):
d
¼ 55.7, 97.5, 106.7, 118.7, 126.1, 127.7, 129.1, 132.9, 137.8, 144.93,
165.6; MS(EI): m/z (%) 324 (99), 322 (Mþ, 100), 290 (24), 288 (24),
226 (26), 197 (39), 154 (45); HRMS(EI): m/z [M]þ calcd for
C
13H11N2O739Br: 321.9953; found: 321.9940.
4.8.12. N-(2-Chlorophenyl)-2-nitroaniline (4s)
4.8.6. N-(4-chlorophenyl)-4-trifluoromethylo-2-nitroaniline (4m)
Orange crystals; mp 83e85 ꢁC; 1H NMR (500 MHz, CDCl3):
Orange crystals; mp 111e115 ꢁC [lit.38 112e113 ꢁC (benzene)]; 1H
NMR (500 MHz, CDCl3):
d
¼ 6.83e6.88 (m, 1 H), 7.13e7.19 (m 1 H),
d
¼ 7.18 (d, J ¼ 8.8 Hz, 1 H), 7.22e7.27 (m, 3 H), 7.42e7.45 (m, 2 H),
7.27e7.32 (m, 1 H), 7.38e7.43 (m, 1 H), 7.47 (dd, J ¼ 8.0, 1.3 Hz, 1 H),
7.56 (dd, J ¼ 8.8, 1.6 Hz, 1 H), 8.51 (s, 1 H), 9.63 (s, 1 H); 13C NMR
7.51 (dd, J ¼ 8.0, 1.6 Hz, 1 H), 8.22 (dd, J ¼ 8.6, 1.7 Hz, 1 H), 9.47 (br s,
(125 MHz, CDCl3):
d
¼ 116.4, 119.8 (q, JCF ¼ 34.7 Hz), 123.3 (q,
1 H); 13C NMR (125 MHz, CDCl3):
d
¼ 116.2, 118.4, 124.4, 126.1, 126.7,
JCF ¼ 272 Hz), 124.8 (q, JCF ¼ 4.6 Hz), 126.5, 130.2, 131.9 (q,
JCF ¼ 3.0 Hz), 131.9, 132.4, 136.1, 144.9.
127.5, 128.7, 130.6, 134.3, 135.6, 136.2, 141.5; MS(EI): m/z (%) 248
(Mþ, 100), 201 (54), 167 (68); HRMS(EI): m/z [M]þ calcd for
MS (EI) m/z (%) ¼ 318 (44), 317 (26), 316 (Mþ, 100), 297 (14), 282
(30), 269 (44), 235 (42), 201 (17); HRMS (EI): m/z [M]þ calcd for
C
12H9N2O325Cl: 248.0353; found: 248.0348.
C
13H8N2O325ClF3: 316.0226, found: 316.0224.
4.8.13. N-(2-t-Butylphenyl)-5-chloro-2-nitroaniline (4t)
Orange crystals; mp 139e140 ꢁC; 1H NMR (500 MHz, CDCl3):
4.8.7. N-(5-Chloro-2-methoxyphenyl)-2-nitro-4-
trifluoromethylaniline (4n)
d
¼ 1.40 (s, 9 H), 6.67 (dd, J ¼ 9.1, 2.2 Hz,1 H), 6.76 (d, J ¼ 2.1 Hz,1 H),
7.18e7.21 (m, 1 H), 7.29e7.32 (m, 2 H), 7.53e7.56 (m, 1 H), 8.16, (d,
Orange crystals; mp 138e143 ꢁC; 1H NMR (500 MHz, CDCl3):
J ¼ 9.1 Hz), 9.6 (br s, 1 H); 13C NMR (125 MHz, CDCl3):
¼ 30.6, 35.1,
d
d
¼ 3.87 (s, 3 H), 6.94 (d, J ¼ 8.8 Hz, 1 H), 7.21 (dd, J ¼ 8.8, 2.5 Hz,
115.4, 117.2, 127.5, 127.6, 127.9, 128.0, 129.3,131.2, 136.3,142.6, 145.2,
149.9; MS(EI): m/z (%) 306 (42), 304 (Mþ, 85), 228 (100); HRMS(EI):
m/z [M]þ calcd for C16H17N2O325Cl: 304.0979; found: 304.0982.
1 H), 7.25 (d, J ¼ 8.8 Hz, 1 H), 7.36 (d, J ¼ 2.5 Hz, 1 H), 7.60 (dd, J ¼ 9.1,
2.0 Hz,1 H), 8.51 (d, J ¼ 1.1 Hz,1 H), 9.59 (s, 1 H); 13C NMR (125 MHz,
CDCl3):
d
¼ 56.0, 112.7, 116.7, 120.0 (q, JCF ¼ 34.3 Hz), 123.3 (q,
JCF ¼ 271 Hz), 123.8, 124.7 (q, JCF ¼ 3.7 Hz), 125.6, 126.5, 127.7, 131.7
(q, JCF ¼ 2.9 Hz), 132.8, 143.9, 151.5; MS(EI): m/z (%) 348 (49), 346
(Mþ, 100), 285 (57), 222 (27); HRMS(EI): m/z [M]þ calcd for
4.8.14. N-(2-t-Butylphenyl)-5-methoxy-2-nitroaniline (4u)
Orange crystals; mp 87e90 ꢁC; 1H NMR (500 MHz, CDCl3):
¼ 1.40 (s, 9H), 3.67 (s, 3 H), 6.12 (d, J ¼ 2.7 Hz,1 H), 6.29 (dd, J ¼ 9.5,
d
C
14H10N2O335ClF3: 346.0332; found: 346.0323.
2.7 Hz, 1 H), 7.22e7.28 (m, 3 H), 7.51e7.55 (m, 1 H), 8.19 (d,
J ¼ 9.5 Hz, 1 H), 9.81 (br s, 1 H); 13C NMR (125 MHz, CDCl3):
¼ 30.6,
d
4.8.8. 3,5-Dichloro-N-(2-Chlorophenyl)-2-nitroaniline (4o)
35.1, 55.6, 97.6, 106.0, 127.2, 127.2, 127.7, 129.0, 129.5, 136.9, 146.9,
147.1, 165.6, one signal missing; MS(EI): m/z (%) 300 (Mþ, 85), 224
(100); HRMS(EI): m/z [M]þ calcd for C17H20N2O3: 300.1474; found:
300.1470.
Orange crystals; mp 99e102 ꢁC; 1H NMR (500 MHz, CDCl3):
d
¼ 6.94 (d, J ¼ 2.2 Hz, 1 H), 7.02 (d, J ¼ 2.2 Hz, 1 H), 7.10e7.13 (m,
2 H), 7.35e7.39 (m, 2 H), 7.44 (br s, 1 H); 13C NMR (125 MHz, CDCl3):
d
¼ 114.7, 121.2, 124.3, 129.7, 130.1, 130.9, 135.7, 137.1, 138.7, 141.3;
MS(EI): m/z (%) 320 (40), 318 (98), 316 (Mþ, 100), 284 (39), 282 (39),
4.8.15. 5-Chloro-N-(2-iodo-4-methylphenyl)-2-nitroaniline (4v)
Yellow crystals; mp 147e149 ꢁC; 1H NMR (500 MHz, CDCl3):
271 (56), 269 (50), 237 (56), 235 (80); HRMS(EI): m/z [M]þ calcd for
C
12H7N2O325Cl3: 315.9573; found: 315.9587.
d
¼ 2.37 (s, 3 H), 6.74 (dd, J ¼ 8.9, 2.0 Hz, 1 H), 6.82 (d, J ¼ 2 Hz, 1 H),
7.25 (d, J ¼ 8.5 Hz, 2 H), 7.80 (s, 1 H), 8.17 (d, J ¼ 8.5 Hz, 1 H), 9.39 (br
s, 1 H); 13C NMR (125 MHz, CDCl3):
4.8.9. 5-Chloro-N-(4-chlorophenyl)-2-nitroaniline (4p)
d
¼ 20.5, 97.4, 115.1, 118.1, 126.2,
Orange crystals; mp 158e159 ꢁC (lit.17b 158e159 ꢁC); 1H NMR
128.1, 130.4, 131.6, 137.2, 138.8, 140.6, 142.4, 143.6; MS(EI): m/z (%)
(500 MHz, CDCl3):
d
¼ 6.75 (dd, J ¼ 9.3, 2.0 Hz, 1 H), 7.08 (d,
390 (36), 388 (Mþ, 100), 216 (47); HRMS(EI): m/z [M]þ calcd for
J ¼ 2.0 Hz, 1 H), 7.20e7.24 (m, 2 H), 7.41e7.44 (m, 2 H), 8.16 (d,
C
13H10N2O325ClI: 387.9476; found: 387.9471.
J ¼ 9.3 Hz, 1 H), 9.46 (br s, 1 H); 13C NMR (125 MHz, CDCl3):
d
¼ 115.1, 118.3, 126.1, 128.2, 130.1, 131.7, 131.8, 136.5, 142.6, 143.5;
4.8.16. N-(4-Methylphenyl)-5-methoxy-2-nitroaniline (4w)
MS(EI): m/z (%) 284 (73), 282 (Mþ,100), 248 (42), 235 (38), 201 (49);
HRMS(EI): m/z [M]þ calcd for C12H8N2O235Cl2: 281.9963; found:
281.9961.
Yellow crystals; mp 87e88 ꢁC; 1H NMR (500 MHz, CDCl3):
d
¼ 2.38 (s, 3 H), 3.72 (s, 3 H), 6.31 (dd, J ¼ 9.5, 2.8 Hz, 1 H), 6.48 (d,
J ¼ 2.8 Hz, 1 H), 7.16e7.24 (m, 4 H), 8.17 (d, 9.5 Hz, 1 H), 9.71 (br s,
1 H); 13C NMR (125 MHz, CDCl3):
d
¼ 21.0, 55.6, 97.1, 106.3, 125.0,
4.8.10. N-(4-Methoxyphenyl)-2-nitroaniline (4q)
127.2, 129.0, 130.3, 135.8, 135.9, 146.2, 165.6; MS(EI): m/z (%) 258
Orange crystals; mp 82e85 ꢁC (lit2 78e79 ꢁC, lit5c 83e86 ꢁC); 1H
(Mþ, 100), 224 (42), 168 (25).
NMR (500 MHz, CDCl3):
d
¼ 3.84 (s, 3 H), 6.71 (ddd, J ¼ 8.7, 7.0,
HRMS(EI): m/z [M]þ calcd for C14H14N2O3: 258.1004; found:
258.1002.
1.2 Hz, 1 H), 6.94e6.98 (m, 2 H), 7.00 (dd, J ¼ 8.7, 1.2 Hz, 1 H),
7.18e7.22 (m, 2 H), 7.32 (ddd, J ¼ 8.7, 7.0, 1.5 Hz, 1 H), 8.19 (dd,
J ¼ 8.7, 1.5 Hz, 1 H), 9.41 (br s, 1 H); 13C NMR (125 MHz, CDCl3):
4.8.17. N-(4-Chlorophenyl)-5-fluoro-2-nitroaniline (4x)
d
¼ 55.5, 115.0, 115.7, 116.7, 126.6, 127.1, 131.2, 132.5, 135.7, 144.5,
Fine orange crystals; mp 143e146 ꢁC [lit.39 149e150 ꢁC
(MeOH)]; IR (KBr): 3321, 3102, 1631, 1572, 1500, 1340, 1253, 1205,
157.9; MS(EI): m/z (%) 244 (Mþ, 100), 229 (51), 210 (26), 182 (36),

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Z. Wrobel et al. / Tetrahedron 72 (2016) 8252e8260
8259
1076, 996, 820, 750 cmꢀ1; 1H NMR (500 MHz, CDCl3):
d
¼ 6.51 (ddd,
d
¼ 1.31 (s, 9 H), 4.42 (br s, 1 H), 6.02 (dd, J ¼ 9.5, 2.4 Hz,1 H), 6.14 (d,
J ¼ 9.6, 2.6, JHF ¼ 7.0 Hz, 1 H), 6.75 (dd, J ¼ 2.6 JHF ¼ 11.1 Hz, 1 H),
J ¼ 2.4 Hz, 1 H), 7.21e7.24 (m, 2 H), 7.36e7.39 (m, 2 H), 8.03 (d,
7.21e7.24 (m, 2 H), 7.40e7.43 (m, 2 H), 8.27 (dd, J ¼ 9.6, JHF ¼ 6.1 Hz,
J ¼ 9.5 Hz, 1 H), 9.87 (br s, 1 H); 13C NMR (125 MHz, CDCl3):
¼ 29.5,
d
1 H), 9.56 (s, 1 H); 13C NMR (125 MHz, CDCl3):
d
¼ 101.3 (d,
51.6, 94.5, 107.9, 124.3, 126.0, 128.9, 129.7, 130.6, 137.7, 145.4, 152.9;
MS(EI): m/z (%) 321 (18), 319 (Mþ, 55), 304 (100); HRMS(EI): m/z
[M]þ calcd for C16H18N3O325Cl: 319.1088; found: 319.1072.
JCF ¼ 28.3 Hz), 106.3 (d, JCF ¼ 24.9), 126.2, 129.9 (d, JCF ¼ 12.4 Hz),
130.0, 130.1, 131.9, 136.6, 145.2 (d, 12.7 Hz), 167.2 (d, JCF ¼ 256 Hz);
MS(EI): m/z (%) 268 (42), 266 (Mþ, 100), 232 (42), 219 (41), 185 (46);
HRMS(EI): m/z [M]þ calcd for C12H835ClFN2O2: 266.0258; found:
266.0264.
4.10.6. 5-n-Butylamino-N-(4-chlorophenyl)-2-nitroaniline (6f)
Yellow crystals; mp 110e112 ꢁC; 1H NMR (500 MHz, CDCl3):
d
¼ 0.93 (t, J ¼ 7.3 Hz, 3 H), 1.33e1.42 (m, 2 H), 1.53e1.59 (m, 2 H),
3.06 (t, J ¼ 7.0 Hz, 2 H), 4.41 (br s, 1 H), 6.0e6.04 (m, 2 H), 7.22e7.25
(m, 2 H), 7.35e7.38 (m, 2 H), 8.05e8.08 (m, 1 H), 9.90 (br s, 1 H); 13
NMR (125 MHz, CDCl3):
4.9. Oxidation of N-aryl-2-nitrosoanilines 5 with IBX. Synthesis of
2-nitrodiarylamines 6
C
d
¼ 13.7, 20.0, 31.1, 42.8, 92.5, 105.9, 124.7,
N-Aryl-2-nitrosoaniline 5 (1 mmol) and IBX (308 mg, 1.1 mmol)
were stirred in DMSO (8 mL) at room temperature for ca. 20 h. The
mixture was then poured into diluted brine and extracted with
EtOAc. The extract was washed with water, brine and dried with
Na2SO4. The solvent was evaporated and the crude product was
purified by column chromatography (SiO2, hexane/EtOAc).
125.9, 129.3, 129.6, 130.5, 137.7, 145.8, 154.2; MS(EI): m/z (%) 321
(25), 319 (Mþ, 77), 276 (100); HRMS(EI): m/z [M]þ calcd for
C
16H18N3O325Cl: 319.1088; found: 319.1088.
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4.10.1. N-(4-Methylphenyl)-2-nitro-5-(pyrrolidin-1-yl)aniline (6a)
Orange crystals; mp 146e148 ꢁC; IR (KBr): 3273, 2973, 2855,
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d
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Yellow crystals; mp 190e192 ꢁC; 1H NMR (500 MHz, CDCl3):
d
¼ 3.22e3.26 (m, 4 H), 3.77e3.81 (m, 4 H), 6.32e6.36 (m, 2 H),
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C
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Yellow crystals; mp 172e176 ꢁC; 1H NMR (500 MHz, CDCl3):
d
¼ 1.98e2.02 (m, 4 H), 3.28e3.32 (m, 4 H), 5.99 (d, J ¼ 2.5 Hz, 1 H),
6.08 (dd, J ¼ 2.5, 9.5 Hz, 1 H), 7.24e7.27 (m, 2 H), 7.34e7.37 (m, 2 H),
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