Synthesis of (alkylamino)nitroarenes by oxidative alkylamination of nitroarenes

Article abstract of DOI:10.1002/ejoc.200800740

The viability of the oxidative alkylamination process for the derivatization of electron-deficient carboaromatics has been investigated. 1,3-Dinitrobenzene, 1-nitronaphthalene, and 1,5- and 1,8-dinitronaphthalenes have shown to react with a wide range of alkylamines in the presence of an oxidant (KMnO₄, AgMnO₄, AgPy₂MnO₄) to give access to the corre sponding N-alkyl-nitroarenamines in moderate to good yields. Nitroarenes are more reactive than azines towards alkylamines.

Full text of DOI:10.1002/ejoc.200800740

FULL PAPER
DOI: 10.1002/ejoc.200800740
Synthesis of (Alkylamino)nitroarenes by Oxidative Alkylamination of
Nitroarenes
Anna V. Gulevskaya,*[a] Stefan Verbeeck,[b] Oleg N. Burov,[a] Caroline Meyers,[b]
Inna N. Korbukova,[a] Wouter Herrebout,[b] and Bert U. W. Maes*[b]
Dedicated to Professor Alexander F. Pozharskii on the occasion of his 70th birthday
Keywords: Aromatic substitution / Amination / Amines / Nucleophilic substitution / Nitroarenes
The viability of the oxidative alkylamination process for the
derivatization of electron-deficient carboaromatics has been
investigated. 1,3-Dinitrobenzene, 1-nitronaphthalene, and
1,5- and 1,8-dinitronaphthalenes have shown to react with
a wide range of alkylamines in the presence of an oxidant
(KMnO4, AgMnO4, AgPy2MnO4) to give access to the corre-
sponding N-alkyl-nitroarenamines in moderate to good
yields. Nitroarenes are more reactive than azines towards
alkylamines.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
adduct, formed in the presence of an excess of nucleophile,
is higher than the oxidation rate of the nucleophile itself.
These a priori rules, especially point (ii), seem difficult to
fulfill. In fact, nucleophiles resistant to oxidation are not
numerous. Ammonia is one such example, though alkyl-
amines are much more sensitive than ammonia towards oxi-
dation. In previous reports from our laboratories,[6] how-
ever, we have shown that an alkylamine/AgPy2MnO4 sys-
tem is very efficient for the oxidative alkylamination of az-
ines. AgPy2MnO4 can thus be regarded as a rather selective
oxidant for this objective. With regard to point (i), mono-
and bicyclic azines and their nitro derivatives were pre-
viously used predominantly as substrates for oxidative
(alkyl)amination. Surprisingly, reports on oxidative (alkyl)-
amination of polynitroarenes, which also possess rather
high π-deficiency, are very scarce. The limited literature pre-
cedents include amination[7] and methylamination[8] of 1,3-
dinitrobenzenes by a classical procedure (RNH2/KMnO4),
butylamination of 1,3-dinitrobenzene and 1,3-dinitronaph-
thalene with the nBuNH2/KMnO4/TBAF/DMF sys-
tem,[9a,9b] and butyl- and hexylamination of 1,3-dinitroben-
zenes, 1,3,5-trinitrobenzene, and 1,3-dinitronaphthalene by
electrochemical rather than chemical oxidation.[9c]
Introduction
The synthesis of functionalized aromatic and heteroaro-
matic amines is still of great interest, due to their impor-
tance as building blocks for pharmaceuticals, agrochem-
icals, polymers, and materials.[1] The classical strategy for
their preparation is based on nucleophilic displacement re-
actions involving good leaving groups. Harsh reaction con-
ditions and strong dependence on the substitution pattern
of the arene substrate are drawbacks limiting its applica-
tion.[2] A more general approach, widely used nowadays, is
Pd-catalyzed coupling between aryl halides and alkyl-
amines.[3] In cases of electron-deficient azaheteroaromatic
substrates, direct oxidative amination and alkylamination
with KNH2/NH3/KMnO4 or alkylamine/KMnO4, pion-
eered by van der Plas,[4b] is an attractive alternative because
no classical leaving group is required. Mechanistically, this
nucleophilic aromatic substitution of hydrogen consists of
σH adduct formation and its subsequent oxidative rearoma-
tization (Scheme 1).[4] Generally, oxidative nucleophilic aro-
matic substitution of hydrogen (ONSH)[5] can be performed
when: i) the electrophilicity of the substrate used is rather
high for providing σH adduct in sufficient concentration,
and ii) either the oxidant is able to oxidize the σH adduct
(not nucleophile) selectively, or the oxidation rate of the σH
[a] Department of Organic Chemistry, Southern Federal Univer-
sity,
Zorge str. 7, Rostov-on-Don 344090, Russian Federation
E-mail: agulevskaya@rsu.ru
[b] Department of Chemistry, University of Antwerp,
Groenenborgerlaan 171, 2020 Antwerp, Belgium
Fax: +32-32653233
Scheme 1. General scheme for the oxidative alkylamination of az-
ines.
E-mail: bert.maes@ua.ac.be
564
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 564–574

Oxidative Alkylamination of Nitroarenes
Attempts to use 1,2- and 1,4-dinitrobenzenes as sub- cause of its oxidizable nature the reaction product 2g was
strates in oxidative methylamination reactions led to nucleo- isolated in 29% yield as a hydrochloride salt (Table 1, En-
philic substitution of nitro groups, yielding N-methyl-2- try 8). 1,3-Dinitrobenzene (1) hardly reacted with second-
nitroaniline and N-methyl-4-nitroaniline, respectively.[8]
ary cyclic amines, as is exemplified by its reaction with
In this paper we describe oxidative alkylaminations of morpholine, giving only a trace of 2h (Table 1, Entry 9).
1,3-dinitrobenzene, 1-nitronaphthalene, and 1,5- and 1,8-di-
nitronaphthalenes by use of alkylamine/KMnO4, alkyl-
amine/AgPy2MnO4, or alkylamine/AgMnO4 systems. The
developed procedures provide access to a wide variety of N-
alkyl-2,4-dinitroanilines, which are of current interest be-
cause of their optical second harmonic generation capabili-
ties[10] and application as components of fluorescent
signaling systems.[11] o-Nitronaphthylamines are interesting
as precursors of the naphthalene “proton sponges” and
polycyclic imidazoles. To the best of our knowledge, the
N-alkyl-1,5-dinitronaphthalen-2-amines,
N-alkyl-1,8-di-
nitronaphthalen-2-amines, and N,NЈ-dialkyl-1,5-dini-
tronaphthalene-2,6-diamines reported in this study have
not been described previously. There are only a few
reports on the synthesis of the parent 1,5-dinitro-
naphthalen-2-amine,[12a,12b] N-alkyl-4,5-dinitronaphthalen-
1-amine,[12c–12e] and N,NЈ-dimethyl-1,5-dinitronaphthalene-
2,6-diamine.[12f,12g]
Scheme 2. Oxidative alkylamination of 1,3-dinitrobenzene (1).
Table 1. Oxidative alkylamination of 1,3-dinitrobenzene (1).
Entry HNR1R2
Product
Oxidant (method)[a] % Yield
1
2
3
EtNH2
nPrNH2
iPrNH2
2a
2b
2c
KMnO4 (A)
KMnO4 (B)
KMnO4 (B)
59
81[b]
63
4
5
6
7
8
9
10
11
12
13
14
15
16
17
nBuNH2
nBuNH2
tBuNH2
cHexNH2
NH2CH2CH2NH2
morpholine
EtNH2
nPrNH2
iPrNH2
nBuNH2
tBuNH2
cHexNH2
NH2CH2CH2NH2
morpholine
2d
2d
2e
KMnO4 (C)
KMnO4 (B)
KMnO4 (B)
KMnO4 (B)
KMnO4 (D)
KMnO4 (B)
AgPy2MnO4 (E)
AgPy2MnO4 (F)
AgPy2MnO4 (F)
AgPy2MnO4 (F)
AgPy2MnO4 (F)
AgPy2MnO4 (F)
AgPy2MnO4 (G)
AgPy2MnO4 (B)
66
Results and Discussion
74[c]
4
The butylamination of 1,3-dinitrobenzene and 1,3-dini-
tronaphthalene by ONSH described above has been re-
ported to be promoted by fluoride ions.[9] However, we
found that 1,3-dinitrobenzene (1) reacts with nBuNH2/
KMnO4/DMF, in the absence of tetrabutylammonium fluo-
ride, to provide a similar yield of N-butyl-2,4-dinitroaniline
(2d, 66% against 63%[9]) (Scheme 2; Table 1, Entry 4). In
fact, the reaction does not require DMF as a cosolvent
either. Treatment of 1 with an excess of butylamine in the
presence of 2 equiv. of KMnO4 (room temp., overnight)
gave 2d in 74% yield, together with diamino derivative 3b
2f
10
29
trace
72
71
73
63
69
63
2g[d]
2h
2a
2b
2c
2d
2e
2f
2g[d]
2h
37
4
[a] Method A, 0–2 °C, overnight; Method B, room temp., over-
(10%) as a minor compound (Table 1, Entry 5). Alkylamin- night; Method C, DMF, room temp., 1.5 h; Method D, THF, room
temp., overnight; Method E, 0–2 °C, 1.5 h; Method F, room temp.,
ation of 1,3-dinitrobenzene (1) with propylamine/KMnO4
proceeded similarly, producing mono- and bis(propyl-
1.5 h; Method G, THF, room temp., overnight. [b] Total yield of
1
2b and 3a (8:1 ratio deduced by H NMR). [c] Compound 3b was
amino) derivatives 2c and 3a in 81% total yield (8:1 ratio
also obtained in 10% yield. [d] Isolated as hydrochloride salt.
as deduced from 1H NMR). Unfortunately, we failed to
separate this mixture (Table 1, Entry 2). The reported oxi-
The use of AgPy2MnO4 instead of KMnO4 led to the
dative amination[7] and methylamination[8] of 1,3-dinitro- desired N-alkyl-2,4-dinitroanilines 2a–g in 37–73% yields
benzene also provided both type of reaction products. (Table 1, Entries 10–16). The reactions required only 1.5 h
Treatment of 1 with the bulkier isopropylamine, tert-bu- at room temperature to give complete conversion, except
tylamine, and cyclohexylamine in the presence of KMnO4 for the reaction involving THF as co-solvent (Table 1, En-
gave no bis(alkylamino) derivatives 3 (Table 1, Entries 3, 6, try 16). tert-Butylamine and cyclohexylamine, which had
7). The yields of the corresponding N-alkyl-2,4-dinitroanil- given poor yields of 2 with KMnO4, smoothly converted
ines 2 vary from 63% (2c) to 4% (2e). As well as steric 1 into 2e and 2f in the presence of AgPy2MnO4 (Table 1,
hindrance, the lower solubility of KMnO4 in tert-bu- Entries 14, 15). However, the yield of 2h is still disappoint-
tylamine and cyclohexylamine and, as a consequence, the ingly low (Table 1, Entry 17). It should be noted that oxi-
lower rate of the oxidation step might explain the lower dative alkylamination with AgPy2MnO4 does not produce
yields obtained. Alkylamination of 1 with ethane-1,2-di- bis(alkylamino) derivatives 3 and is therefore more selective
amine/KMnO4 was carried out in THF as a co-solvent in towards the desired compounds. Compounds 3 are formed
order to avoid the need for removal of a large excess of by subsequent oxidative alkylamination of monoalkylamino
ethane-1,2-diamine after completion of the reaction. Be- derivatives 2. To verify this, N-butyl-2,4-dinitroaniline (2d)
Eur. J. Org. Chem. 2009, 564–574
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
565

A. V. Gulevskaya, B. U. W. Maes et al.
FULL PAPER
was treated with nBuNH2 in the presence of KMnO4 Table 2. Oxidative alkylamination of 1,5-dinitronaphthalene (4).
(2 equiv., room temp., overnight). From the 1H NMR spec-
Entry
HNR1R2
Product
Oxidant[a] (method)[b] % Yield
troscopic data we were able to deduce that 40% of the start-
ing material had been converted into bis(butylamino) deriv-
ative 3b. Unfortunately, though, we were unable to push the
reaction to completion, as longer reaction times or in-
creased amounts of KMnO4 (4–6 equiv.) afforded 3b in
practically the same yields.
1
2
3
4
5
6
7
8
9
EtNH2
5a
5b
5c
5a
5b
5c
6a
6b
6c
KMnO4 (A)
KMnO4 (A)
KMnO4 (A)
AgPy2MnO4 (B)
AgPy2MnO4 (B)
AgPy2MnO4 (B)
AgMnO4 (C)
AgMnO4 (C)
AgMnO4 (C)
35
48
42
59
60
60
13
16
10
nPrNH2
nBuNH2
EtNH2
nPrNH2
nBuNH2
EtNH2
1,5-Dinitronaphthalene (4) seems to be more reactive
towards alkylamines than 1,3-dinitrobenzene. Treatment of
4 with propylamine and KMnO4 carried out at room tem-
perature gave a mixture of products that we failed to sepa-
rate. However, use of THF as a co-solvent and a reduction
in the reaction temperature to –15 to –12 °C allowed con-
version of 4 into the desired 1,5-dinitro-N-propylnaph-
thalen-2-amine (5b) in 48% yield (Scheme 3, Table 2, En-
try 2). Treatment of 4 with ethylamine and butylamine gave
5a and 5c in 35 and 42% yields, respectively (Table 2, En-
tries 1, 3). As had been observed for 1, substrate 4 gave
faster reactions when AgPy2MnO4 was used as the oxidant
than with KMnO4 (Table 2, Entries 4–6). Moreover, slightly
higher yields of 5a–c were obtained. When AgPy2MnO4
was used, however, the transformations of 4 into 5 were
nPrNH2
nBuNH2
[a] 2 and 3 equiv. of the oxidant were used for the synthesis of 5 and
6, respectively. [b] Method A, THF, –15 to –12 °C, 24 h; Method B,
THF, –15 to –12 °C, 2 h; Method C, –15 to –12 °C, 48 h.
accompanied by further alkylamination of 5. Prolongation
of the reaction over 3 h led to accumulation of 2,6-bis(alkyl-
amino) derivatives 6 and partial tarring of the reaction mix-
tures. Compounds 6a–c were obtained in low yields when
the reactions were performed in the appropriate alk-
ylamines in the presence of AgMnO4 (4 equiv.) at low tem-
peratures (–15 to –12 °C) for long reaction times (48 h,
Table 2, Entries 7–9). Compound 6b was also obtained by
treatment of monoalkylamino derivative 5b with propyl-
amine under similar conditions in 30% yield. Similarly,
treatment of 5b with butylamine gave the asymmetrical bis-
(alkylamino) derivative 6d in 25% yield.
Theoretically, the oxidative alkylamination of 1,5-di-
nitronaphthalene (4) can proceed at position 2 as well as at
position 4. The structural assignments for compounds 5
1
and 6 were based on the H NMR spectroscopic data. The
8-H proton of 5 reveals itself as a doublet of multiplets at
8.8–8.9 ppm (Figure 1). Obviously, this high δ value is the
result of the deshielding influence of the peri NO2 group.
The multiplet form of the 8-H signal is due to long-range
Scheme 3. Oxidative alkylamination of 1,5-dinitronaphthalene (4).
1
Figure 1. Fragment of the H NMR spectrum of compound 5a (CDCl3).
566
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 564–574

Oxidative Alkylamination of Nitroarenes
spin-spin coupling between this proton and both the 6-H ative 8e in 14% yield (Table 3, Entries 5 and 6). Generally,
and 4-H nuclei. The magnitude of the allylic (4J6,8) and the reducing the reaction temperature to –15 to –12 °C de-
homoallylic coupling constants (5J4,8) are 0.6–1.0 Hz, which creased the yields but did not significantly influence the ra-
is in accordance with literature data.[13] Other protons ap- tios of the products (Table 3, Entries 7–9). In no cases were
pear upfield from 8-H at 7.2–8.4 ppm. Notably, the magni- bis(alkylamino) derivatives observed (Scheme 4).
tude of the J3,4 coupling constant (9.8–10.1 Hz) is larger
than those of J7,8 (8.8 Hz) and J6,7 (7.6 Hz). This is the
result of strong conjugation of the 1-NO2 group and the 2-
Table 3. Oxidative alkylamination of 1,8-dinitronaphthalene (7).
Entry
HNR1R2
Oxidant
Ratio[b] % Yield[c]
alkylamino fragment. The observed δ values for the NH-
protons of 5a–c (8.3–8.5 ppm) are in agreement with this.
1H–1H COSY experiments provided unambiguous discrimi-
nation between all signals (Figure 2) and confirmed the
long-range couplings. The 1H NMR spectra of N,NЈ-di-
alkyl-1,5-dinitronaphthalene-2,6-diamines 6 are rather sim-
ple. Each displays a set of the signals belonging to the alk-
ylamino group and two doublet signals of the 3(7)-H and
4(8)-H protons at δ = 7.1 and 8.6 ppm, respectively, with a
coupling constant of 9.7 Hz. This justifies the symmetry of
the molecular structures of 6a–c. Other spectroscopic and
spectrometric data (IR, UV, and MS) are in full agreement
with the proposed structures of 5 and 6.
(method)[a]
8/9
8
9
1
2
3
4
5
6
7
8
9
nPrNH2
nPrNH2
nPrNH2
nBuNH2
cHexNH2
morpholine AgMnO4 (A)
EtNH2
KMnO4 (A)
AgPy2MnO4 (B) 1:1.2
AgMnO4 (A)
AgMnO4 (A)
AgMnO4 (C)
1:1. 3
16
11
38
32
40
14
12
15
23
22
10
53
38
trace
–
16
30
1
1:1.4
1:1.2
1:0
1:0
1:1.3
1:2
AgMnO4 (D)
AgMnO4 (D)
AgMnO4 (D)
nPrNH2
cHexNH2
37:1
[a] Method A, room temp., overnight; Method B, THF, –15 to
–12 °C, overnight; Method C, THF, room temp., overnight;
Method D, –15 to –12 °C, overnight. [b] 1H NMR ratio of the reac-
tion mixture before separation. [c] Isolated yield after separation of
8 and 9.
Scheme 4. Oxidative alkylamination of 1,8-dinitronaphthalene (7).
To find the scope and limitations of the developed pro-
cedure we also tested nitrobenzene and 1-nitronaphthalene
as substrates. Nitrobenzene (10) hardly reacted with bu-
tylamine/KMnO4 (room temp., 24 h), giving a mixture of
isomeric N-butyl-2-nitroaniline (11) and N-butyl-4-nitro-
aniline (12) in less than 1% yield. The use of AgPy2MnO4
as the oxidant did not increase the yields significantly. In
1
Figure 2. Fragment of the H-1H COSY NMR spectrum of com-
pound 5a (CDCl3).
Treatment of 1,8-dinitronaphthalene (7) with propyl- contrast, 1-nitronaphthalene (13) demonstrated a higher re-
amine and KMnO4 gave 1,8-dinitro-N-propylnaphthalen-2- activity. When treated with butylamine/AgPy2MnO4, 13
amine (8b) and 4,5-dinitro-N-propylnaphthalen-1-amine was converted into a mixture of the o- and p-butylamino
1
(9b) in 38% total yield (1:1.3 ratio deduced by H NMR) derivatives 14b and 15b in 73% total yield (Scheme 5,
(Table 3, Entry 1). Treatment of 7 with propylamine/Ag- Table 4, Entry 2). Oxidation with KMnO4 gave both prod-
Py2MnO4 at room temperature gave a complicated mixture ucts in only 15% total yield (Table 4, Entry 1). Treatment
of products that we failed to separate. The use of THF as of 13 with propylamine/AgPy2MnO4 proceeded similarly,
co-solvent and reduction of the reaction temperature to –15 affording 1-nitro-N-propylnaphthalen-2-amine (14a) and 4-
to –12 °C provided propylamino derivatives 8b and 9b in nitro-N-propylnaphthalen-1-amine (15a) (Table 4, Entry 3).
11% and 10% yields, respectively (Table 3, Entry 2). Per- Pyrimidine (16), which can be regarded as a heterocyclic
forming the reaction in propylamine at room temperature analogue of 1,3-dinitrobenzene, did not react with alk-
with AgMnO4 as oxidant provided significantly higher ylamines in the presence of KMnO4 or AgPy2MnO4 as the
yields of 8b and 9b, but the selectivity did not improve oxidant. Quinoline (19) was significantly less reactive than
(Table 3, Entry 3). Treatment of 7 with butylamine gave a 1-nitronaphthalene. When treated with propylamine/Ag-
similar result (Table 3, Entry 4). Interestingly, cyclohex- Py2MnO4 (room temp., 24 h), 19 was converted into a mix-
ylamine and morpholine gave exclusively 2-cyclohex- ture of isomeric N-propyl(quinolin-2-yl)amine and -(quin-
ylamino derivative 8d in 40% yield and 2-morpholino deriv- olin-4-yl)amine in 3% total yield (1:1 ratio).
Eur. J. Org. Chem. 2009, 564–574
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
567

A. V. Gulevskaya, B. U. W. Maes et al.
FULL PAPER
in 1,8-dinitronaphthalene (7) is also slightly higher than ωk
for C-2, which is in accordance with the general observation
that mixtures of compounds alkylaminated at C-2 and C-4
are formed. Of course, one has to be very careful in ration-
alizing regioselectivities only on this basis because the oxi-
dation potentials of the different σ adducts formed can play
a major role, it being likely that this step is rate-limiting in
the oxidative (alkyl)amination process.
Scheme 5. Oxidative alkylamination of 1-nitronaphthalene (13).
Table 4. Oxidative alkylamination of 1-nitronaphthalene (13).
Entry
RNH2
Oxidant (method)[a]
% Yield
14
15
1
2
3
nBuNH2
nBuNH2
nPrNH2
KMnO4 (A)
AgPy2MnO4 (B)
AgPy2MnO4 (B)
12
52
49
3
21
22
[a] Method A, room temp., 24 h; Method B, room temp., 24 h.
Figure 4. Calculated global electrophilicity values (ω, in eV) and
local electrophilicity indices (ωk, given at each ring atom, in eV).
On the basis of our earlier work[5f] we tried to explain
the observed regioselectivities by calculating and analyzing
the spatial distributions of the Fukui functions for nucleo-
philic attack (fk+) on the dinitroarenes (1, 4, and 7) experi- Conclusions
mentally studied as substrates, using DFT calculations at
A simple and efficient synthetic route to N-alkyl-2,4-dini-
the B3LYP/6–31G** level (Gaussian 03[14]). The results of
the calculation of the global and local electrophilicity in-
dices (ω and ωk[15]) for preliminary optimized structures of
the nitroarenes (Figure 3) are presented in Figure 4. For
1,3-dinitrobenzene (1) the maximum of ωk corresponds to
C-4, which is indeed the reaction site. Although the local
electrophilicity index of C-4 in 1,5-dinitronaphthalene (4) is
slightly higher than ωk for C-2, the alkylamination exclu-
sively occurs at C-2. This can be explained by taking ac-
count of the steric hindrance of the peri-nitro group, disfav-
oring attack at C-4. The local electrophilicity index of C-4
troanilines, N-alkyl-1-nitronaphthalen-2-amines, N-alkyl-4-
nitronaphthalen-1-amines, N-alkyl-1,n-dinitronaphthalen-
2-amines (n = 5,8), N-alkyl-4,5-dinitronaphthalen-1-amines,
and
N,NЈ-dialkyl-1,5-dinitronaphthalene-2,6-diamines
through oxidative alkylamination of the corresponding ni-
troarenes has been elaborated. The method allows the use
of a wide range of primary aliphatic amines, especially
when AgPy2MnO4 is used as the oxidant. The protocol pre-
sented here provides yields of alkylamino products the same
as – or, more often, superior to – those of classical synthetic
procedures for N-alkyl-2,4-dinitroanilines based on nucleo-
philic aromatic substitution in the corresponding 1-X-2,4-
dinitrobenzenes,[10,11a,16] N-alkylation of 2,4-dinitroanil-
ine,[17] and oxidative N-dealkylation of N,N-dialkyl-2,4-di-
nitroanilines,[18] and distinguishes itself in very mild reac-
tion conditions and the use of a commercially available
starting compound (1,3-dinitrobenzene). The chemical oxi-
dation method presented in this paper seems to be more
attractive than the electrochemical oxidation of σ adducts
of 1,3-dinitrobenzenes and alkylamines[9c] because it pro-
vides superior yields of N-alkyl-2,4-dinitroanilines and it
does not require the use of special equipment.
Experimental Section
General: All melting points were determined in glass capillaries and
are uncorrected. The 1H and 13C NMR spectra were recorded with
a Bruker 250 (250 MHz) instrument in the solvent indicated and
with TMS as an internal standard. All coupling constants are given
in Hertz, and chemical shifts are given in parts per million (ppm).
Infrared (IR) spectra were recorded with a Specord IR-71 spec-
trometer (Nujol). Ultraviolet absorption (UV) spectra were regis-
tered with a Specord M-40 spectrophotometer in CHCl3 as a sol-
vent. Mass spectra were measured on a Finnigan MAT INCOS 50
spectrometer. Nitroarenes, pyrimidine, and alkylamines (Acros and
Figure 3. B3LYP/6-31G(d,p) equilibrium geometries (left) and cor-
responding Fukui functions (right) for nucleophilic attack on 1,3-
dinitrobenzene (1, top), 1,5-dinitronaphthalene (4, middle), and
1,8-dinitronaphthalene (7, bottom). The values for the isodensity
3
surfaces were set to 0.005 e a0 .
568
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 564–574

Oxidative Alkylamination of Nitroarenes
Aldrich) were obtained from commercial sources and used as such.
AgPy2MnO4 was prepared from AgNO3, pyridine, and KMnO4 by
a literature procedure.[19] Flash column chromatography was per-
formed on silica gel and Al2O3 (III–IV activity, Brockman) with
chloroform or dichloromethane as eluents.
The reaction with morpholine was carried out in a similar way for
16 h at room temperature to give 2h.
The reaction with ethylamine gave 2a (Method E).
Method G: Procedure similar to Method D, but AgPy2MnO4
(0.770 g, 2 mmol) was used as the oxidant. The reaction gave com-
pound 2g (97 mg, 37%).
General Procedures for the Oxidative Alkylamination of 1,3-Dinitro-
benzene (1)
N-Ethyl-2,4-dinitroaniline (2a): Yield 124 mg, 59% (Method A);
152 mg, 72% (Method B). Bright yellow needles with m.p. 112–
114 °C (hexane; ref.[16c] 90 °C). 1H NMR (250 MHz, CDCl3,
30 °C): δ = 9.13 (d, J = 2.7 Hz, 1 H, 3-H), 8.48 (br., 1 H, NH),
8.26 (dd, J = 9.6, 2.7 Hz, 1 H, 5-H), 6.90 (d, J = 9.6 Hz, 1 H, 6-
Method A: Procedure similar to Method B, but reaction temp. 0–
2 °C. The reaction with ethylamine gave compound 2a.
Method B: KMnO4 (316 mg, 2 mmol) was added at room tempera-
ture in small portions over 1 h to a stirred solution of 1,3-dinitro-
benzene (1, 168 mg, 1 mmol) in the appropriate alkylamine
(10 mL). The reaction mixture was stirred overnight. The excess of
the alkylamine was subsequently removed under reduced pressure.
The residue was ground with silica gel (3–4 g), introduced onto a
silica gel column (3.5ϫ30 cm), and purified by flash column
chromatography with dichloromethane as the eluent. A bright yel-
low fraction gave the corresponding N-alkyl-2,4-dinitroaniline (2).
Upon butylamination of 1 the first bright yellow fraction gave N-
butyl-2,4-dinitroaniline (2d, 177 mg, 74%) and the next yellow frac-
tion gave N,NЈ-dibutyl-4,6-dinitrobenzene-1,3-diamine (3b, 31 mg,
10%). The crude product was crystallized from hexane.
H), 3.45 (m,
2 H, CH2CH3), 1.42 (t, J = 7.3 Hz, 3 H,
CH CH ) ppm. IR (Nujol): ν = 3367 (N–H), 3106 (C–H arom.),
˜
2
3
1610 and 1573 (C–C arom.), 1520 and 1500 (NO2, as), 1333 and
1300 (NO2, s) cm–1. UV (CHCl3): λmax (lg ε) = 246 (4.38), 258 sh
(3.97), 357 (4.32), 415 sh nm (3.92). MS (70 eV): m/z (%) = 211 (63)
[M]+, 196 (92), 164 (14), 150 (22), 132 (13), 118 (53), 92 (48), 78
(100), 63 (54), 52 (34), 46 (40). C8H9N3O4 (211.17): calcd. C 45.50,
H 4.30, N 19.90; found C 45.63, H 4.19, N 19.97.
2,4-Dinitro-N-propylaniline (2b): Yield 160 mg, 71% (Method F).
Bright yellow needles with m.p. 98–99 °C (hexane; ref.[10] 100–
102 °C). 1H NMR (250 MHz, CDCl3, 30 °C): δ = 9.13 (d, J =
2.8 Hz, 1 H, 3-H), 8.56 (br., 1 H, NH), 8.25 (dd, J = 9.5, 2.8 Hz,
1 H, 5-H), 6.91 (d, J = 9.5 Hz, 1 H, 6-H), 3.37 (m, 2 H,
CH2CH2CH3), 1.80 (m, 2 H, CH2CH2CH3), 1.07 (t, J = 7.4 Hz, 3
Method C: KMnO4 (158 mg, 1 mmol) was added to a stirred solu-
tion of 1,3-dinitrobenzene (1, 168 mg, 1 mmol) and butylamine
(0.49 mL, 5 mmol) in DMF (3 mL). After 1.5 h stirring at room
temperature the reaction mixture was diluted with water (5 mL)
and extracted with dichloromethane (3ϫ20 mL). The extract was
dried with MgSO4. The solvent was subsequently removed under
reduced pressure. The residue was ground with silica gel (3–4 g),
introduced onto a silica gel column (3.5ϫ30 cm), and purified by
flash column chromatography with dichloromethane as the eluent.
A bright yellow fraction was separated. The crude product was
crystallized from heptane to yield N-butyl-2,4-dinitroaniline (2d,
158 mg, 66%).
H, CH CH CH ) ppm. IR (Nujol): ν = 3360 (N–H), 3100 (C–H
˜
2
2
3
arom.), 1620 and 1580 (C–C arom.), 1520–1490 (NO2, as), 1333
and 1305 (NO2, s) cm–1. UV (CHCl3): λmax (lg ε) = 246 (4.73),
263 sh (4.43), 361 (4.55), 414 sh nm (4.13). MS (70 eV): m/z (%):
225 (22) [M]+, 196 (100), 150 (10), 104 (10), 77 (10). C9H11N3O4
(225.20): calcd. C 48.00, H 4.92, N 18.66; found C 47.89, H 4.77,
N 18.53.
N-Isopropyl-2,4-dinitroaniline (2c): Yield 142 mg, 63% (Method B);
164 mg, 73% (Method F). Bright yellow needles with m.p. 95–
1
Method D: KMnO4 (316 mg, 2 mmol) was added in small portions
over 1 h to a stirred solution of 1,3-dinitrobenzene (1, 168 mg,
1 mmol) and ethane-1,2-diamine (2 mL) in THF (5 mL). The reac-
tion mixture was stirred overnight, and the solvents were evapo-
rated. The residue was extracted with boiling iPrOH (100 mL). The
solvent was subsequently removed under reduced pressure, and
water (20 mL) was added to the residue. The mixture was heated
to boiling and filtered (to remove a tar), and the filtrate was cooled
quickly. The precipitate was separated by filtration, mixed immedi-
ately with iPrOH (20 mL), and acidified to pH 2 with conc. HCl.
The precipitate was separated by filtration and rinsed with iPrOH
and then Et2O. N-(2-Aminoethyl)-2,4-dinitroaniline hydrochloride
(2g) was obtained in 29% (76 mg) yield.
96 °C (hexane). H NMR (250 MHz, CDCl3, 30 °C): δ = 9.13 (d,
J = 2.5 Hz, 1 H, 3-H), 8.49 (br., 1 H, NH), 8.24 (dd, J = 9.5,
2.5 Hz, 1 H, 5-H), 6.91 (d, J = 9.5 Hz, 1 H, 6-H), 3.92 [m, 1 H,
CH(CH3)2], 1.38 [t, J = 6.3 Hz, 6 H, CH(CH3)2] ppm. IR (Nujol):
ν = 3327 (N–H), 3126 (C–H arom.), 1627 and 1590 (C–C arom.),
˜
1527–1500 (NO2, as), 1333 and 1300 (NO2, s) cm–1. MS (70 eV):
m/z (%) = 225 (31) [M]+, 210 (100), 164 (26), 134 (18), 118 (25), 91
(22), 75 (11), 63 (14), 43 (22). C9H11N3O4 (225.20): calcd. C 48.00,
H 4.92, N 18.66; found C 47.94, H 5.06, N 18.83.
N-Butyl-2,4-dinitroaniline (2d): Yield 177 mg, 74% (Method B);
158 mg, 66% (Method C); 151 mg, 63% (Method F). Bright yellow
needles with m.p. 90–91 °C (hexane; ref.[10] 92–94 °C). 1H NMR
(250 MHz, CDCl3, 30 °C): δ = 9.13 (d, J = 2.8 Hz, 1 H, 3-H), 8.54
(br., 1 H, NH), 8.25 (dd, J = 9.5, 2.8 Hz, 1 H, 5-H), 6.90 (d, J =
9.5 Hz, 1 H, 6-H), 3.39 (m, 2 H, CH2CH2CH2CH3), 1.74 (m, 2 H,
CH2CH2CH2CH3), 1.49 (m, 2 H, CH2CH2CH2CH3), 0.99 (t, J =
The reaction with AgPy2MnO4 (0.770 g, 2 mmol) was carried out
in a similar way (Method G) to give 2g (97 mg, 37%).
Method E: Procedure similar to Method F, but reaction temp. 0–
2 °C.
7.3 Hz, 3 H, CH CH CH CH ) ppm. IR (Nujol): ν = 3353 (N–H),
˜
2
2
2
3
3113 (C–H arom.), 1620 and 1587 (C–C arom.), 1516–1490 (NO2,
as), 1328 and 1317 (NO2, s) cm–1. UV (CHCl3): λmax (lg ε) = 246
(4.96), 263 sh (4.64), 362 (4.81), 419 sh nm (4.45). MS (70 eV): m/z
(%) = 239 (17) [M]+, 196 (100), 150 (15), 104 (10). C10H13N3O4
(239.23): calcd. C 50.21, H 5.48, N 17.56; found C 50.04, H 5.62,
N 17.71.
Method F: AgPy2MnO4 (0.770 g, 2 mmol) was added in small por-
tions at room temperature over 1 h to a stirred solution of 1,3-
dinitrobenzene (1, 168 mg, 1 mmol) in the appropriate alkylamine
(10 mL). After 1.5 h overall stirring time the excess of the alk-
ylamine was removed under reduced pressure. The residue was
ground with silica gel (3–4 g), introduced onto a silica gel column
(3.5ϫ30 cm), and purified by flash column chromatography with
chloroform as the eluent. A bright yellow fraction gave the corre-
sponding N-alkyl-2,4-dinitroaniline (2). The crude product was
crystallized from hexane.
N-tert-Butyl-2,4-dinitroaniline (2e): Yield 9.6 mg, 4% (Method B);
165 mg, 69% (Method F). Bright yellow needles with m.p. 151–
1
153 °C (hexane). H NMR (250 MHz, CDCl3, 30 °C): δ = 9.14 (d,
J = 2.7 Hz, 1 H, 3-H), 8.88 (br., 1 H, NH), 8.20 (dd, J = 9.5,
Eur. J. Org. Chem. 2009, 564–574
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
569

A. V. Gulevskaya, B. U. W. Maes et al.
FULL PAPER
2.7 Hz, 1 H, 5-H), 7.14 (d, J = 9.5 Hz, 1 H, 6-H), 1.54 [s, 6 H,
(2.5ϫ40 cm), and purified by flash column chromatography with
C(CH ) ] ppm. IR (Nujol): ν = 3340 (N–H), 3140 (C–H arom.), CHCl3 as the eluent. The first bright yellow fraction, preceding the
˜
3 3
1627 and 1587 (C–C arom.), 1513 and 1500 (NO2, as), 1333 and
1310 (NO2, s) cm–1. UV (CHCl3): λmax (lg ε) = 248 (4.66), 263 sh
(4.51), 362 (4.61), 421 sh nm (4.30). MS (70 eV): m/z (%) = 239 (22)
[M]+, 224 (100), 183 (28), 57 (25), 41 (19). C10H13N3O4 (239.23):
calcd. C 50.21, H 5.48, N 17.56; found C 50.35, H 5.57, N 17.40.
crimson one, gave N-alkyl-1,5-dinitronaphthalen-2-amine (5). The
crude product was crystallized from iPrOH.
Method B: The reactions with KMnO4 (316 mg, 2 mmol) were car-
ried out in a similar way at –15 to –12 °C for 24 h.
Method C: AgMnO4 (680 mg, 3 mmol) was added in small portions
at –15 to –12 °C over 1 h to a stirred solution of 1,5-dinitro-
naphthalene (4, 218 mg, 1 mmol) in the appropriate alkylamine
(15 mL). After 48 h overall stirring the reaction mixture was con-
centrated (without heating) under reduced pressure. The residue
was ground with Al2O3 (3–4 g), introduced onto an Al2O3 column
(2.5ϫ40 cm), and purified by flash column chromatography with
CHCl3 as the eluent. The crimson fraction gave N,NЈ-dialkyl-1,5-
dinitronaphthalene-2,6-diamine (6). The crude product was crys-
tallized from MeOH.
N-Cyclohexyl-2,4-dinitroaniline (2f): Yield 26.5 mg, 10%
(Method B); 167 mg, 63% (Method F). Bright yellow needles with
m.p. 151–153 °C (hexane; ref.[16c] 110 °C). 1H NMR (250 MHz,
CDCl3, 30 °C): δ = 9.13 (d, J = 2.8 Hz, 1 H, 3-H), 8.60 (br., 1 H,
NH), 8.21 (dd, J = 9.8, 2.8 Hz, 1 H, 5-H), 6.91 (d, J = 9.8 Hz, 1
H, 6-H), 3.60 (m, 1 H, cyclo-C6H11), 2.05 (m, 2 H, cyclo-C6H11),
1.81 (m, 2 H, cyclo-C6H11), 1.68 (m, 2 H, cyclo-C6H11), 1.44 (m, 4
H, cyclo-C H ) ppm. IR (Nujol): ν = 3353 (N–H), 3113 (C–H
˜
6
11
arom.), 1620 (and 1587 (C–C arom.), 1513–1490 (NO2, as), 1333
and 1290 (NO2, s) cm–1. UV (CHCl3): λmax (lg ε) = 247 (4.86),
264 sh (4.41), 364 (4.55), 422 sh nm (4.24). MS (70 eV): m/z (%) =
265 (26) [M]+, 222 (100), 179 (25), 149 (10), 130 (20), 105 (12), 78
(12), 63 (10), 55 (18), 41 (19). C12H15N3O4 (265.27): calcd. C 54.33,
H 5.70, N 15.84; found C 54.18, H 5.57, N 16.00.
N-Ethyl-1,5-dinitronaphthalen-2-amine (5a): Yield 154 mg, 59%
(Method A); 91 mg, 35% (Method B). Bright yellow crystals with
1
m.p. 142–144 °C (iPrOH). H NMR (250 MHz, CDCl3, 30 °C): δ
= 8.81 (d, J = 8.8 Hz, 1 H, 8-H), 8.39 (d, J = 9.8 Hz, 1 H, 4-H),
8.30 (br., 1 H, NH), 7.88 (dd, J = 7.6, 1.0 Hz, 1 H, 6-H), 7.60 (dd,
J = 8.8, 7.6 Hz, 1 H, 7-H), 7.26 (d, J = 9.8 Hz, 1 H, 3-H), 3.50
(dq, J = 5.1, 7.2 Hz, 2 H, CH2CH3), 1.41 (t, J = 7.1 Hz, 3 H,
N-(2-Aminoethyl)-2,4-dinitroaniline Hydrochloride (2g): Yield
76 mg, 29% (Method D); 97 mg, 37% (Method G). Bright yellow
solid with m.p. 267–268 °C (ref.[11a] 268–270 °C). 1H NMR
(250 MHz, [D6]DMSO): δ = 8.80 (d, J = 2.7 Hz, 1 H, 3-H), 8.25
(d, J = 9.5 Hz, 1 H, 5-H), 7.98 (br., 3 H, NH2 + NH), 7.30 (d, J
= 9.5 Hz, 1 H, 6-H), 3.75 (m, 2 H, CH2CH2NH2), 3.00 (m, 2 H,
CH CH ) ppm. IR (Nujol): ν = 3340 (N–H), 1627 and 1567 (C–C
˜
2
3
arom.), 1527–1500 (NO2, as), 1343 and 1313 (NO2, s) cm–1. UV
(CHCl3): λmax (lg ε) = 258 sh (4.26), 278 (4.43), 345 (3.86), 426 sh
(3.70), 471 nm (3.88). MS (70 eV): m/z (%) = 261 (100) [M]+, 246
(18), 182 (14), 169 (33), 154 (49), 140 (53), 127 (55), 114 (57), 102
(34), 87 (25), 75 (44), 70 (11), 63 (53), 51 (25), 43 (47), 39 (19).
C12H11N3O4 (261.23): calcd. C 55.17, H 4.24, N 16.09; found C
55.01, H 4.13, N 15.95.
CH2CH2NH2) ppm. IR (Nujol):
ν = 3353 and 3280–3300
˜
(N–H), 3110 (C–H arom.), 1617 and 1587 (C–C arom.), 1520 and
1500 (NO2, as), 1340 and 1317 (NO2, s) cm–1. MS (70 eV): m/z (%)
= 226 (10) [M]+, 197 (11), 179 (46), 152 (26), 150 (13), 104 (40), 77
(64), 66 (20), 63 (32), 51 (55), 43 (16), 42 (13), 38 (46), 36 (100).
C8H11ClN4O4 (262.65): calcd. C 36.58, H 4.22, Cl 13.50, N 21.33;
found C 36.72, H 4.31, Cl 13.39, N 21.46.
1,5-Dinitro-N-propylnaphthalen-2-amine (5b): Yield 165 mg, 60%
(Method A); 132 mg, 48% (Method B). Bright yellow crystals with
1
m.p. 122–124 °C (iPrOH). H NMR (250 MHz, CDCl3, 30 °C): δ
4-(2,4-Dinitrophenyl)morpholine (2h): Yield 10 mg, 4% (Method F).
Bright yellow needles with m.p. 117–118 °C (hexane). 1H NMR
(250 MHz, CDCl3, 30 °C): δ = 8.69 (d, J = 2.8 Hz, 1 H, 3-H), 8.27
(dd, J = 9.2, 2.8 Hz, 1 H, 5-H), 7.09 (d, J = 9.2 Hz, 1 H, 6-H), 3.85
[t, J = 4.7 Hz, 4 H, O(CH2)2], 3.25 [t, J = 4.7 Hz, 4 H, N-
= 8.85 (d, J = 8.8 Hz, 1 H, 8-H), 8.46 (br., 1 H, NH), 8.39 (d, J =
9.8 Hz, 1 H, 4-H), 7.89 (dd, J = 7.6, 1.0 Hz, 1 H, 6-H), 7.61 (dd,
J = 8.8, 7.6 Hz, 1 H, 7-H), 7.28 (d, J = 9.8 Hz, 1 H, 3-H), 3.42 (dt,
J = 5.4, 7.0 Hz, 2 H, CH2CH2CH3), 1.79 (m, 2 H, CH2CH2CH3),
1.07 (t, J = 7.3 Hz, 3 H, CH CH CH ) ppm. IR (Nujol): ν = 3347
˜
2
2
3
(CH ) ] ppm. IR (Nujol): ν = 3113 (C–H arom.), 1607 and 1587
˜
(N–H), 1633 and 1567 (C–C arom.), 1540–1520 (NO2, as), 1360
and 1327 (NO2, s) cm–1. UV (CHCl3): λmax (lg ε) = 258 sh (4.28),
277 (4.45), 346 (3.90), 421 sh (3.86), 472 nm (3.89). MS (70 eV):
m/z (%) = 275 (88) [M]+, 246 (100), 172 (37), 153 (37), 140 (22),
127 (34), 114 (23), 102 (10), 75 (14), 63 (16), 43 (13), 41 (18).
C13H13N3O4 (275.26): calcd. C 56.72, H 4.76, N 15.27; found C
56.87, H 4.59, N 15.14.
2 2
(C–C arom.), 1533 and 1507 (NO2, as), 1340–1327 (NO2, s) cm–1.
C10H11N3O5 (253.21): calcd. C 47.43, H 4.38, N 16.59; found C
47.29, H 4.19, N 16.44.
N,NЈ-Dibutyl-2,4-dinitrobenzene-1,3-diamine (3b): Bright yellow
needles with m.p. 76–78 °C (heptane). 1H NMR (250 MHz, CDCl3,
30 °C): δ = 9.59 (br., 1 H, BuNH-3), 8.21 (d, J = 10.1 Hz, 1 H, 5-
H), 7.85 (br., 1 H, BuNH-1), 6.09 (d, J = 10.1 Hz, 1 H, 6-H), 3.31
(m, 2 H, CH2CH2CH2CH3), 2.92 (m, 2 H, CH2CH2CH2CH3), 1.67
(m, 4 H, 1- and 3-NHCH2CH2CH2CH3), 1.40 (m, 4 H, 1- and 3-
NHCH2CH2CH2CH3), 0.97 (t, J = 7.4 Hz, 3 H, CH2CH2CH2-
N-Butyl-1,5-dinitronaphthalen-2-amine (5c): Yield 173 mg, 60%
(Method A); 121 mg, 42% (Method B). Bright yellow crystals with
1
m.p. 110–112 °C (iPrOH). H NMR (250 MHz, CDCl3, 30 °C): δ
= 8.81 (d, J = 8.8 Hz, 1 H, 8-H), 8.45 (br., 1 H, NH), 8.38 (d, J =
10.1 Hz, 1 H, 4-H), 7.88 (dd, J = 7.6, 1.0 Hz, 1 H, 6-H), 7.59 (dd,
J = 8.8, 7.6 Hz, 1 H, 7-H), 7.27 (d, J = 10.1 Hz, 1 H, 3-H), 3.45
(dt, J = 5.4, 7.0 Hz, 2 H, CH2CH2CH2CH3), 1.74 (m, 2 H,
CH2CH2CH2CH3), 1.48 (m, 2 H, CH2CH2CH2CH3), 0.98 (t, J =
CH3), 0.91 (t,
J = 7.4 Hz, 3 H, CH2CH2CH2CH3) ppm.
C14H22N4O4 (310.35): calcd. C 54.18, H 7.15, N 18.05; found C
54.01, H 7.29, N 18.21.
General Procedures for the Oxidative Alkylamination of 1,5-Dini-
tronaphthalene
7.3 Hz, 3 H, CH CH CH CH ) ppm. IR (Nujol): ν = 3347 (N–
˜
2
2
2
3
H), 1633 and 1560 (C–C arom.), 1530–1513 (NO2, as), 1360 and
1327 (NO2, s) cm–1. UV (CHCl3): λmax (lg ε) = 258 sh (4.28), 283
(4.48), 339 (3.96), 421 sh (3.80), 471 nm (3.94). MS (70 eV): m/z
(%) = 289 (62) [M]+, 246 (86), 172 (41), 153 (48), 140 (29), 127
Method A: AgPy2MnO4 (0.770 g, 2 mmol) was added in small por-
tions at –15 to –12 °C, over 1 h, to a stirred solution of 1,5-dini-
tronaphthalene (4, 218 mg, 1 mmol) and alkylamine (3 mL) in THF
(15 mL). After 2 h overall stirring time the reaction mixture was (63), 114 (53), 102 (29), 75 (50), 63 (55), 55 (20), 51 (28), 41 (100).
concentrated (without heating) under reduced pressure. The residue
was ground with Al2O3 (3–4 g), introduced onto an Al2O3 column
C14H15N3O4 (289.29): calcd. C 58.13, H 5.23, N 14.53; found C
58.21, H 5.37, N 14.39.
570
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 564–574

Oxidative Alkylamination of Nitroarenes
N,NЈ-Diethyl-1,5-dinitronaphthalene-2,6-diamine (6a): Yield 40 mg,
13% (Method A). Red crystals with m.p. 214–216 °C (MeOH). H
NMR (250 MHz, CDCl3, 30 °C): δ = 8.56 [d, J = 9.7 Hz, 1 H, 4-
H (8-H)], 7.87 (br., 1 H, NH), 7.14 [d, J = 9.7 Hz, 1 H, 3-H (7-H)],
1313 (NO2, s) cm–1. UV (CHCl3): λmax (lg ε) = 260 sh (4.28), 279 sh
(4.58), 293 (4.73), 338 sh (4.30), 502 sh (4.12), 562 nm (4.25). MS
(70 eV): m/z (%) = 346 (71) [M]+, 227 (13), 182 (18), 169 (32), 155
(16), 140 (16), 127 (17), 114 (16), 100 (10), 77 (12), 63 (12), 57 (27),
1
3.50 (m, 2 H, CH2CH3), 1.37 (t, J = 7.2 Hz, 3 H, CH2CH3) ppm. 55 (16), 43 (65), 41 (100). C17H22N4O4 (346.38): calcd. C 58.95, H
IR (Nujol): ν = 3373 (N–H), 1600 (C–C arom.), 1493 (NO , as),
6.40, N 16.17; found C 59.08, H 6.27, N 16.31.
˜
2
1313 (NO2, s) cm–1. UV (CHCl3): λmax (lg ε) = 265 sh (4.26), 278 sh
(4.65), 292 (4.77), 335 sh (4.46), 500 sh (4.10), 564 nm (4.15). MS
(70 eV): m/z (%) = 304 (100) [M]+, 224 (11), 213 (10), 197 (23), 183
(44), 169 (64), 156 (58), 154 (57), 140 (61), 127 (57), 114 (56), 101
(40), 88 (28), 78 (32), 76 (48), 70 (12), 63 (53), 51 (31), 42 (51), 38
(12). C14H16N4O4 (304.30): calcd. C 55.26, H 5.30, N 18.41; found
C 55.39, H 5.44, N 18.23.
General Procedures for the Oxidative Alkylamination of 1,8-Dini-
tronaphthalene
Method A: AgMnO4 (454 mg, 2 mmol) was added in small portions
over 3 h at room temperature to a stirred solution of 1,8-dini-
tronaphthalene (7, 218 mg, 1 mmol) in an alkylamine (15 mL). Af-
ter stirring overnight the reaction mixture was concentrated under
reduced pressure. The residue was ground with Al2O3 (3–4 g), intro-
duced onto an Al2O3 column (3ϫ35 cm) and purified by flash col-
umn chromatography with CHCl3 as the eluent. The first bright
yellow fraction gave the N-alkyl-1,8-dinitronaphthalen-2-amine (8).
The second bright yellow fraction gave the N-alkyl-4,5-dini-
tronaphthalen-1-amine (9). The crude products were crystallized
from MeOH.
1,5-Dinitro-N,NЈ-dipropylnaphthalene-2,6-diamine
(6b):
Yield
53 mg, 16% (Method A). Red crystals with m.p. 186–188 °C
(MeOH). 1H NMR (250 MHz, CDCl3, 30 °C): δ = 8.56 [d, J =
9.7 Hz, 1 H, 4-H (8-H)], 8.00 (br., 1 H, NH), 7.14 [d, J = 9.7 Hz,
1 H, 3-H (7-H)], 3.35 (m, 2 H, CH2CH2CH3), 1.76 (m, 2 H,
CH2CH2CH3), 1.05 (t, J = 7.4 Hz, 3 H, CH2CH2CH3) ppm. IR
(Nujol): ν = 3373 (N–H), 1607 (C–C arom.), 1493 (NO , as), 1327
˜
2
(NO2, s) cm–1. UV (CHCl3): λmax (lg ε) = 258 sh (4.59), 278 sh
(4.74), 287 (4.80), 335 sh (4.40), 502 sh (4.03), 562 nm (4.18). MS
(70 eV): m/z (%) = 332 (100) [M]+, 303 (14), 227 (13), 213 (10), 182
(17), 169 (28), 156 (10), 154 (12), 140 (12), 137 (13), 127 (11), 114
(10), 43 (33), 41 (28). C16H20N4O4 (332.35): calcd. C 57.82, H 6.07,
N 16.86; found C 57.98, H 5.92, N 16.74.
Method B: AgMnO4 (454 mg, 2 mmol) was added at room tem-
perature in small portions over 3 h to a stirred solution of 1,8-
dinitronaphthalene (7, 218 mg, 1 mmol) and cyclohexylamine
(3 mL) in THF (15 mL). After stirring overnight the reaction mix-
ture was concentrated under reduced pressure. Further workup was
similar to Method A.
N,NЈ-Dibutyl-1,5-dinitronaphthalene-2,6-diamine (6c): Yield 36 mg,
10% (Method A). Red crystals with m.p. 169–171 °C (MeOH). H
Method C: The reaction was carried out similarly to Method A at
–15 to –12 °C.
1
NMR (250 MHz, CDCl3, 30 °C): δ = 8.55 [d, J = 9.7 Hz, 1 H, 4-
H (8-H)], 7.99 (br., 1 H, NH), 7.13 [d, J = 9.7 Hz, 1 H, 3-H (7-H)],
3.38 (m, 2 H, CH2CH2CH2CH3), 1.71 (m, 2 H, CH2CH2CH2CH3),
1.46 (m, 2 H, CH2CH2CH2CH3), 0.97 (t, J = 7.4 Hz, 3 H,
Method D: The reaction was carried out similarly to Method B
at –15 to –12 °C with 1,8-dinitronaphthalene (7, 218 mg, 1 mmol),
propylamine (3 mL), THF (15 mL) and AgPy2MnO4 (0.770 g,
2 mmol).
CH CH CH CH ) ppm. IR (Nujol): ν = 3360 (N–H), 1620 (C–C
˜
2
2
2
3
arom.), 1507 (NO2, as), 1313 (NO2, s) cm–1. UV (CHCl3): λmax
(lg ε) = 258 sh (4.32), 278 sh (4.50), 292 (4.68), 338 sh (4.36), 500 sh
(4.11), 564 nm (4.26). MS (70 eV): m/z (%) = 360 (89) [M]+, 169
(20), 155 (10), 154 (10), 140 (10), 127 (10), 83 (10), 77 (10), 71 (12),
69 (21), 57 (44), 55 (29), 44 (76), 41 (100), 39 (24). C18H24N4O4
(360.41): calcd. C 59.99, H 6.71, N 15.55; found C 60.14, H 6.53,
N 15.38.
N-Ethyl-1,8-dinitronaphthalen-2-amine (8a): Yield 32 mg, 12%
(Method C). Orange crystals with m.p. 223–225 °C decomp.
(MeOH). H NMR (250 MHz, CDCl3, 30 °C): δ = 8.31 (br., 1 H,
NH), 8.12 (dd, J = 7.7, 1.4 Hz, 1 H, 7-H), 7.87 (dd, J = 7.7, 1.4 Hz,
1 H, 5-H), 7.85 (d, J = 9.5 Hz, 1 H, 4-H), 7.38 (t, J = 7.7 Hz, 1 H,
6-H), 7.19 (d, J = 9.5 Hz, 1 H, 3-H), 3.50 (m, 2 H, CH2CH3), 1.40
1
(t, J = 7.2 Hz, 3 H, CH CH ) ppm. IR (Nujol): ν = 3343 (N–H),
˜
2
3
3092 (C–H arom.), 1633 and 1558 (C–C arom.), 1524 (NO2, as),
1356 (NO2, s) cm–1. UV (CHCl3): λmax (lg ε) = 260 (4.61), 314
(3.92), 424 nm (3.95). MS (70 eV): m/z (%) = 261 (35) [M]+, 215
(31), 198 (69), 185 (100), 170 (78), 156 (23), 139 (14), 129 (22), 115
(54), 102 (34), 88 (11), 75 (18), 63 (19), 51 (13), 39 (10). C12H11N3O4
(261.23): calcd. C 55.17, H 4.24, N 16.09; found C 55.36, H 4.02,
N 16.23.
General Procedures for the Oxidative Alkylamination of N-Alkyl-
1,5-dinitronaphthalen-2-amines: AgMnO4 (0.454 g, 2 mmol) was
added in small portions at –15 to –12 °C, over 1 h, to a stirred
solution of an N-alkyl-1,5-dinitronaphthalen-2-amine (5, 1 mmol)
and alkylamine (30 mL). After 24 h overall stirring time the reac-
tion mixture was concentrated (without heating) under reduced
pressure. The residue was ground with Al2O3 (3–4 g), introduced
onto an Al2O3 column (2.5ϫ40 cm), and purified by flash column
chromatography with CHCl3 as the eluent. The crimson fraction
gave the N,NЈ-dialkyl-1,5-dinitronaphthalene-2,6-diamines 6b
(30%) or 6d (25%). The crude product was crystallized from
iPrOH. Compound 6b was identical to that obtained by alkylamin-
ation of 1,5-dinitronaphthalene (Method C).
1,8-Dinitro-N-propylnaphthalen-2-amine (8b): Yield 105 mg, 35%
(Method A); 41 mg, 15% (Method C); 30 mg, 11% (Method D).
Orange crystals with m.p. 174–175 °C (MeOH). 1H NMR
(250 MHz, CDCl3, 30 °C): δ = 8.43 (br., 1 H, NH), 8.12 (dd, J =
7.8, 1.3 Hz, 1 H, 7-H), 7.87 (dd, J = 7.8, 1.3 Hz, 1 H, 5-H), 7.84
(d, J = 9.4 Hz, 1 H, 4-H), 7.37 (t, J = 7.8 Hz, 1 H, 6-H), 7.19 (d,
J = 9.4 Hz, 1 H, 3-H), 3.41 (dt, J = 5.3, 7.2 Hz, 2 H, CH2CH2CH3),
N-Butyl-1,5-dinitro-NЈ-propylnaphthalene-2,6-diamine (6d): Red
crystals with m.p. 168–169 °C (MeOH). 1H NMR (250 MHz, 1.79 (m,
2
H, CH2CH2CH3), 1.07 (t,
J
=
7.4 Hz,
3 H,
CDCl3, 30 °C): δ = 8.57 (pseudodoublet, J = 9.7 Hz, 2 H, 4-H and
8-H), 8.00 (br., 2 H, 2ϫNH), 7.14 (pseudodoublet, J = 10.0 Hz, 2
CH CH CH ) ppm. IR (Nujol): ν = 3345 (N–H), 1627 and 1567
˜
2
2
3
(C–C arom.), 1513 (NO2, as), 1353 (NO2, s) cm–1. UV (CHCl3):
H, 3-H and 7-H), 3.37 (m,
CH2CH2CH3), 1.74 (m, 4 H, CH2CH2CH2CH3 and CH2CH2CH3), (%) = 275 (48) [M]+, 229 (38), 199 (100), 184 (20), 170 (62), 156
1.46 (m, 2 H, CH2CH2CH2CH3), 1.04 (t, J = 7.2 Hz, 3 H, (12), 143 (16), 130 (20), 115 (51), 102 (29), 89 (11), 75 (16), 63 (18),
CH2CH2CH3), 0.97 (t, J = 7.2 Hz, 3 H, CH2CH2CH2CH3) ppm. 51 (12), 41 (30). C13H13N3O4 (275.26): calcd. C 56.72, H 4.76, N
IR (Nujol): ν = 3344 (N–H), 1624 (C–C arom.), 1496 (NO , as), 15.27; found C 56.81, H 4.90, N 15.39.
4 H, CH2CH2CH2CH3 and λmax (lg ε) = 261 (4.54), 315 (3.83), 425 nm (3.88). MS (70 eV): m/z
˜
2
Eur. J. Org. Chem. 2009, 564–574
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
571

A. V. Gulevskaya, B. U. W. Maes et al.
FULL PAPER
N-Butyl-1,8-dinitronaphthalen-2-amine (8c): Yield 92 mg, 32%
5.26 (br., 1 H, NH), 3.35 (m, 2 H, CH2CH2CH3), 1.83 (m, 2 H,
CH2CH2CH3), 1.10 (t, J = 7.5 Hz, 3 H, CH2CH2CH3) ppm. IR
(Method A). Orange crystals with m.p. 119–120 °C (MeOH). 1H
NMR (250 MHz, CDCl3, 30 °C): δ = 8.38 (br., 1 H, NH), 8.12 (dd, (Nujol): ν = 3405 (N–H), 1620 and 1573 (C–C arom.), 1520 (NO ,
˜
2
J = 7.7, 1.4 Hz, 1 H, 7-H), 7.86 (dd, J = 8.1, 1.4 Hz, 1 H, 5-H),
7.84 (d, J = 9.5 Hz, 1 H, 4-H), 7.37 (dd, J = 7.7, 8.1 Hz, 1 H, 6-
H), 7.19 (d, J = 9.5 Hz, 1 H, 3-H), 3.44 (dt, J = 5.6, 7.0 Hz,
2 H, CH2CH2CH2CH3), 1.75 (m, 2 H, CH2CH2CH2CH3), 1.48
as), 1359 and 1306 (NO2, s) cm–1. UV (CHCl3): λmax (lg ε) = 265
(4.13), 336 sh (3.47), 420 nm (4.12). MS (70 eV): m/z (%) = 275 (28)
[M]+, 229 (23), 199 (100), 170 (22), 157 (12), 142 (13), 129 (32), 115
(23), 102 (19), 75 (14), 63 (14), 41 (32). C13H13N3O4 (275.26): calcd.
C 56.72, H 4.76, N 15.27; found C 56.55, H 4.59, N 15.41.
(m,
2 H, CH2CH2CH2CH3), 0.98 (t, J = 7.4 Hz, 3 H,
CH CH CH CH ) ppm. IR (Nujol): ν = 3347 (N–H), 3071 (C–H
˜
2
2
2
3
N-Butyl-4,5-dinitronaphthalen-1-amine (9c): Yield 110 mg, 38%
(Method A). Orange crystals, decomp. Ͼ180 °C (MeOH; ref.[12d]
197 °C). 1H NMR (250 MHz, CDCl3, 30 °C): δ = 8.30 (d, J =
8.8 Hz, 1 H, 3-H), 8.19 (d, J = 7.7 Hz, 1 H, 6-H), 8.03 (d, J =
8.1 Hz, 1 H, 8-H), 7.57 (t, J = 8.1 Hz, 1 H, 7-H), 6.57 (d, J =
8.8 Hz, 1 H, 2-H), 5.23 (br., 1 H, NH), 3.38 (dt, J = 5.3, 7.0 Hz, 2
H, CH2CH2CH2CH3), 1.79 (m, 2 H, CH2CH2CH2CH3), 1.52 (m,
arom.), 1638 (C–C arom.), 1527 (NO2, as), 1350 (NO2, s) cm–1. UV
(CHCl3): λmax (lg ε) = 260 (4.50), 314 (3.79), 426 nm (3.84). MS
(70 eV): m/z (%) = 289 (51) [M]+, 243 (43), 213 (100), 201 (10), 184
(25), 170 (62), 155 (16), 143 (20), 130 (27), 115 (58), 102 (29), 89
(221), 75 (14), 63 (15), 41 (40). C14H15N3O4 (289.29): calcd. C
58.13, H 5.23, N 14.53; found C 57.95, H 5.01, N 14.68.
N-Cyclohexyl-1,8-dinitronaphthalen-2-amine (8d): Yield 126 mg,
2
H, CH2CH2CH2CH3), 1.01 (t,
J
=
7.4 Hz,
3
H,
40% (Method B); 72 mg, 23% (Method C). Orange crystals with
m.p. 166–168 °C (MeOH). H NMR (250 MHz, CDCl3, 30 °C): δ
= 8.50 (br. d, J = 6.7 Hz, 1 H, NH), 8.11 (dd, J = 7.7, 1.4 Hz, 1
H, 7-H), 7.85 (dd, J = 7.7, 1.4 Hz, 1 H, 5-H), 7.80 (d, J = 9.5 Hz,
1 H, 4-H), 7.35 (t, J = 7.7 Hz, 1 H, 6-H), 7.20 (d, J = 9.5 Hz, 1 H,
CH CH CH CH ) ppm. IR (Nujol): ν = 3412 (N–H), 3101 (C–
˜
2
2
2
3
1
H arom.), 1624 and 1570 (C–C arom.), 1531 (NO2, as), 1360 and
1300 (NO2, s) cm–1. UV (CHCl3): λmax (lg ε) = 264 (4.16), 331 sh
(3.45), 420 nm (4.14). MS (70 eV): m/z (%) = 289 (20) [M]+, 243
(17), 213 (100), 170 (11), 129 (14), 115 (11), 41 (12). C14H15N3O4
3-H), 3.65 (m, 1 H, cyclo-C6H11), 2.06 (m, 2 H, cyclo-C6H11), 1.82 (289.29): calcd. C 58.13, H 5.23, N 14.53; found C 58.26, H 5.39,
(m, 2 H, cyclo-C6H11), 1.67 (m, 2 H, cyclo-C6H11), 1.44 (m, 4 H, N 14.39.
cyclo-C H ) ppm. IR (Nujol): ν = 3345 (N–H), 3075 (C–H arom.),
˜
6
11
N-Cyclohexyl-4,5-dinitronaphthalen-1-amine (9d): Yield 31 mg, 1%
(Method C). Orange crystals, decomp. Ͼ160 °C (MeOH). 1H
NMR (250 MHz, CDCl3, 30 °C): δ = 8.29 (d, J = 9.1 Hz, 1 H, 3-
H), 8.18 (dd, J = 7.7, 1.0 Hz, 1 H, 6-H), 8.03 (dd, J = 8.8, 1.0 Hz,
1 H, 8-H), 7.56 (dd, J = 7.7, 8.8 Hz, 1 H, 7-H), 6.59 (d, J = 9.1 Hz,
1 H, 2-H), 5.20 (br. d, J = 7.0 Hz, 1 H, NH), 3.58 (m, 2 H, cyclo-
C6H11), 2.16 (m, 2 H, cyclo-C6H11), 1.86 (m, 2 H, cyclo-C6H11),
1.69 (m, 2 H, cyclo-C6H11), 1.40 (m, 4 H, cyclo-C6H11) ppm. IR
1633 and 1559 (C–C arom.), 1531 and 1519 (NO2, as), 1350
(NO2, s) cm–1. UV (CHCl3): λmax (lg ε) = 262 (4.51), 315 (3.80),
429 nm (3.86). MS (70 eV): m/z (%) = 315 (69) [M]+, 269 (80), 252
(17), 239 (97), 196 (23), 187 (26), 171 (35), 157 (100), 139 (25), 130
(36), 102 (26), 81 (16), 63 (13), 41 (84). C16H17N3O4 (315.32): calcd.
C 60.94, H 5.43, N 13.33; found C 61.16, H 5.19, N 13.07.
4-(1,8-Dinitro-2-naphthyl)morpholine (8e): Yield 43 mg, 14%
(Method A). Orange crystals with m.p. 185–187 °C (MeOH). 1H
NMR (250 MHz, CDCl3, 30 °C): δ = 8.50 (dd, J = 8.6, 1.2 Hz, 1
H, 7-H), 8.25 (d, J = 8.4 Hz, 1 H, 4-H), 8.23 (dd, J = 7.5, 1.2 Hz,
1 H, 5-H), 7.67 (dd, J = 7.5, 8.6 Hz, 1 H, 6-H), 7.17 (d, J = 8.4 Hz,
1 H, 3-H), 4.00 [m, 2 H, O(CH2)2], 3.19 [m, 2 H, N(CH2)2] ppm.
(Nujol): ν = 3401 (N–H), 1572 (C–C arom.), 1530 (NO , as), 1363
˜
2
(NO2, s) cm–1. UV (CHCl3): λmax (lg ε) = 262 (4.30), 336 sh (3.67),
425 nm (4.12). MS (70 eV): m/z (%) = 315 (4), [M]+, 239 (14), 167
(12), 157 (16), 149 (33), 128 (15), 98 (20), 89 (19), 83 (59), 67 (16),
55 (100), 41 (86). C16H17N3O4 (315.32): calcd. C 60.94, H 5.43, N
13.33; found C 60.71, H 5.60, N 13.52.
IR (Nujol): ν = 3104 (C–H arom.), 1564 (C–C arom.), 1528 and
˜
1514 (NO2, as), 1342–1327 (NO2, s) cm–1. UV (CHCl3): λmax (lg ε)
= 256 (4.06), 322 sh (3.59), 385 nm (3.88). MS (70 eV): m/z (%) =
303 (13) [M]+, 257 (19), 227 (100), 169 (32), 141 (22), 114 (50), 88
(11), 75 (12), 63 (15), 42 (11). C14H13N3O5 (303.27): calcd. C 55.45,
H 4.32, N 13.86; found C 55.29, H 4.07, N 13.98.
Oxidative Butylamination of Nitrobenzene: KMnO4 (790 mg,
5 mmol) was added in small portions at room temperature over 3 h
to a stirred solution of nitrobenzene (615 mg, 5 mmol) in bu-
tylamine (10 mL). After 24 h overall stirring the reaction mixture
was concentrated (without heating) under reduced pressure. The
N-Ethyl-4,5-dinitronaphthalen-1-amine (9a): Yield 42 mg, 16% residue was ground with silica gel (3–4 g), introduced onto a silica
(Method C). Orange crystals with m.p. 204–206 °C decomp.
gel column (3ϫ35 cm), and purified by flash column chromatog-
(MeOH). 1H NMR (250 MHz, CDCl3, 30 °C): δ = 8.31 (d, J = raphy with CHCl3/hexane (1:1) as the eluent. The first bright yellow
9.1 Hz, 1 H, 3-H), 8.21 (dd, J = 7.7, 1.0 Hz, 1 H, 6-H), 8.06 (dd, fraction gave N-n-butyl-2-nitroaniline (11). Yield 29 mg (0.3%).
1
J = 8.4, 1.0 Hz, 1 H, 8-H), 7.59 (dd, J = 7.7, 8.4 Hz, 1 H, 7-H),
Orange oil. H NMR (250 MHz, CDCl3, 30 °C): δ = 8.15 (dd, J =
6.58 (d, J = 9.1 Hz, 1 H, 2-H), 5.16 (br., 1 H, NH), 3.44 (m, 2 H, 8.4, 1.7 Hz, 1 H, 3-H), 8.04 (br., 1 H, NH), 7.41 (ddd, J = 7.1, 8.8,
CH CH ), 1.46 (t, J = 7.2 Hz, 3 H, CH CH ) ppm. IR (Nujol): ν 1.7 Hz, 1 H, 5-H), 6.83 (d, J = 8.8 Hz, 1 H, 6-H), 6.60 (ddd, J =
˜
2
3
2
3
= 3412 (N–H), 3102 (C–H arom.), 1624 and 1572 (C–C arom.), 7.1, 8.4, 1.4 Hz, 1 H, 4-H), 3.28 (m, 2 H, CH2CH2CH2CH3), 1.70
1535 (NO2, as), 1353 and 1300 (NO2, s) cm–1. UV (CHCl3): λmax
(lg ε) = 266 (4.14), 336 sh (3.46), 418 nm (4.12). MS (70 eV): m/z
(m, 2 H, CH2CH2CH2CH3), 1.47 (m, 2 H, CH2CH2CH2CH3), 0.97
(t, J = 7.2 Hz, 3 H, CH CH CH CH ) ppm. IR (Nujol): ν = 3382
˜
2
2
2
3
(%) = 261 (10) [M]+, 215 (30), 185 (100), 170 (59), 156 (23), 142 (N–H), 3086 (C–H arom.), 1620 and 1574 (C–C arom.), 1515 (NO2,
(16), 128 (50), 115 (36), 102 (28), 75 (16), 63 (12). C12H11N3O4 as), 1355 (NO2, s) cm–1. UV (CHCl3): λmax (lg ε) = 283 (3.88),
(261.23): calcd. C 55.17, H 4.24, N 16.09; found C 55.09, H 4.39,
N 16.30.
435 nm (3.92). MS (70 eV): m/z (%) = 194 (18) [M]+, 151 (100), 119
(10), 111 (10), 105 (16), 97 (21), 93 (24), 77 (19), 71 (50), 57 (71),
51 (11), 43 (89). C10H14N2O2 (194.23): calcd. C 61.84, H 7.27, N
14.42; found C 62.03, H 7.11, N 14.29.
4,5-Dinitro-N-propylnaphthalen-1-amine (9b): Yield 146 mg, 53%
(Method A); 82 mg, 30% (Method C), 27 mg, 10% (Method D).
1
Orange crystals, decomp. Ͼ190 °C (MeOH). H NMR (250 MHz,
The second bright yellow fraction was eluted with CHCl3 to give
CDCl3, 30 °C): δ = 8.30 (d, J = 9.0 Hz, 1 H, 3-H), 8.19 (dd, J = N-butyl-4-nitroaniline (12). Yield 39 mg (0.4%). The crude product
7.5, 1.3 Hz, 1 H, 6-H), 8.04 (dd, J = 8.5, 1.3 Hz, 1 H, 8-H), 7.57 was crystallized from iPrOH. Orange crystals with m.p. 55–57 °C
1
(dd, J = 7.5, 8.5 Hz, 1 H, 7-H), 6.58 (d, J = 9.0 Hz, 1 H, 2-H),
(MeOH; ref.[20] 54–55 °C). H NMR (250 MHz, CDCl3, 30 °C): δ
572
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 564–574

Oxidative Alkylamination of Nitroarenes
= 8.07 (d, J = 9.3 Hz, 2 H, 3-H and 5-H), 6.50 (d, J = 9.3 Hz, 2
= 230 (70) [M]+, 201 (37), 184 (100), 154 (55), 140 (11), 127 (17),
1 H, NH), 3.19 (m, 2 H, 115 (18), 77 (10), 63 (13), 41 (22). C13H14N2O2 (230.26): calcd. C
H, 2-H and 6-H), 4.46 (br.,
CH2CH2CH2CH3), 1.62 (m, 2 H, CH2CH2CH2CH3), 1.43 (m, 67.81, H 6.13, N 12.17; found C 67.58, H 6.02, N 11.98.
H, CH2CH2CH2CH3), 0.96 (t, 7.2 Hz, H,
CH CH CH CH ) ppm. IR (Nujol): ν = 3346 (N–H), 3065 (C–H
2
J
=
3
N-Butyl-4-nitronaphthalen-1-amine (15b): Yield 8 mg, 3% (Method
A); 51 mg, 21% (Method B). Orange crystals, Ͼ160 °C decomp.
(MeOH; ref.[12d] 158–159 °C). 1H NMR (250 MHz, CDCl3, 30 °C):
δ = 9.03 (d, J = 8.8 Hz, 1 H, 5-H), 8.47 (d, J = 8.8 Hz, 1 H, 3-H),
7.79 (d, J = 8.4 Hz, 1 H, 8-H), 7.68 (dd, J = 6.9, 8.8 Hz, 1 H, 6-
H), 7.51 (dd, J = 6.9, 8.4 Hz, 1 H, 7-H), 6.48 (d, J = 8.8 Hz, 1 H,
2-H), 5.26 (br., 1 H, NH), 3.38 (m, 2 H, CH2CH2CH2CH3), 1.78
(m, 2 H, CH2CH2CH2CH3), 1.52 (m, 2 H, CH2CH2CH2CH3), 1.01
˜
2
2
2
3
arom.), 1608 (C–C arom.), 1462 (NO2, as), 1320 (NO2, s) cm–1. UV
(CHCl3): λmax (lg ε) = 312 sh (3.30), 380 nm (4.26). MS (70 eV):
m/z (%) = 194 (39) [M]+, 151 (100), 105 (60). C10H14N2O2 (194.23):
calcd. C 61.84, H 7.27, N 14.42; found C 61.66, H 7.42, N 14.25.
General Procedures for the Oxidative Alkylamination of 1-Nitro-
naphthalene
(t, J = 7.4 Hz, 3 H, CH CH CH CH ) ppm. IR (Nujol): ν = 3400
˜
2
2
2
3
Method A: KMnO4 (316 mg, 2 mmol) was added in small portions
at room temperature over 3 h to a stirred solution of 1-nitron-
aphthalene (13, 173 mg, 1 mmol) in butylamine (8 mL). After 24 h
overall stirring time the reaction mixture was concentrated under
reduced pressure. The residue was ground with silica gel (3–4 g),
introduced onto a silica gel column (3ϫ35 cm), and purified by
flash column chromatography with CHCl3/CCl4 (4:1) as the eluent.
The first bright yellow fraction gave N-butyl-1-nitronaphthalen-2-
amine (14). The second bright yellow fraction gave N-butyl-4-ni-
tronaphthalen-1-amine (15). The crude products were crystallized
from iPrOH.
(N–H), 1574 (C–C arom.) cm–1. UV (CHCl3): λmax (lg ε) = 266
(3.63), 324 (3.11), 334 (3.11), 425 nm (3.83). MS (70 eV): m/z (%)
= 244 (79) [M]+, 201 (41), 184 (100), 154 (43), 127 (10), 41 (10).
C14H16N2O2 (244.29): calcd. C 68.83, H 6.60, N 11.47; found C
68.68, H 6.47, N 11.64.
Acknowledgments
The authors acknowledge the Russian Foundation for Basic Rese-
arches (grant no. 07-03-00485-a), the Special Research Fund of the
University of Antwerp (BOF UA) and the Flemish Government
(Impulsfinanciering van de Vlaamse Overheid voor Strategisch Ba-
sisonderzoek PFEU 2003) for financial support of this work. C. M.
thanks the Fund for Scientific Research – Flanders (FWO-Flan-
ders) for a postdoctoral grant.
Method B: The reaction was carried out similarly with AgPy2MnO4
(462 mg, 1.2 mmol) as the oxidant.
1-Nitro-N-propylnaphthalen-2-amine (14a): Yield 113 mg, 49%
(Method B). Orange crystals with m.p. 84–85 °C (MeOH). 1H
NMR (250 MHz, CDCl3, 30 °C): δ = 8.95 (br., 1 H, NH), 8.77 (d,
J = 8.7 Hz, 1 H, 8-H), 7.78 (d, J = 9.3 Hz, 1 H, 4-H), 7.64 (d, J =
7.9 Hz, 1 H, 5-H), 7.59 (ddd, J = 7.3, 8.7, 1.5 Hz, 1 H, 7-H), 7.31
(ddd, J = 7.3, 7.9, 1.0 Hz, 1 H, 6-H), 7.05 (d, J = 9.3 Hz, 1 H, 3-
H), 3.40 (m, 2 H, CH2CH2CH3), 1.78 (m, 2 H, CH2CH2CH3), 1.06
[1] a) E. J. Corey, B. Czakó, L. Kürti, Molecules and Medicine,
Wiley, Hoboken, New Jersey, 2007; b) A. S. Travis, in The
Chemistry of Anilines, Patai Series The Chemistry of Functional
Groups (Ed.: Z. Rappoport), Wiley, Chichester, 2007, part 2,
chapter 13, p. 715–782.
(t, J = 7.4 Hz, 3 H, CH CH CH ) ppm. IR (Nujol): ν = 3364 (N–
˜
2
2
3
H), 3052 (C–H arom.), 1635 and 1562 (C–C arom.), 1522 (NO2,
as), 1336 (NO2, s) cm–1. UV (CHCl3): λmax (lg ε) = 263 (4.12), 318
(3.70), 334 (3.68), 423 nm (4.25). C13H14N2O2 (230.26): calcd. C
67.81, H 6.13, N 12.17; found C 68.01, H 6.00, N 12.32.
[2] M. V. Gorelik, L. S. Efros, Osnovy Khimii i Tekhnologii Aro-
maticheskikh Soedinenii (Principles of the Chemistry and Tech-
nology of Aromatic Compounds), Khimia, Moscow, 1992.
[3] a) A. R. Muci, S. L. Buchwald, Top. Curr. Chem. 2002, 219,
131–209; b) B. Schlummer, U. Scholz, Adv. Synth. Catal. 2004,
346, 1599–1626; c) J. F. Hartwig, Synlett 2006, 1283–1294.
[4] a) O. N. Chupakhin, V. N. Charushin, H. van der Plas, Nucleo-
philic Aromatic Substitution of Hydrogen, Academic Press, San
Diego, 1994; b) H. C. van der Plas, Adv. Heterocycl. Chem.
2004, 86, 1–40.
N-Butyl-1-nitronaphthalen-2-amine (14b): Yield 29 mg, 12%
(Method A); 127 mg, 52% (Method B). Orange crystals with m.p.
1
67–69 °C (MeOH). H NMR (250 MHz, CDCl3, 30 °C): δ = 8.92
(br., 1 H, NH), 8.77 (d, J = 8.8 Hz, 1 H, 8-H), 7.78 (d, J = 9.5 Hz,
1 H, 4-H), 7.65 (d, J = 7.7 Hz, 1 H, 5-H), 7.58 (dd, J = 7.4, 8.8 Hz,
1 H, 7-H), 7.31 (dd, J = 7.4, 7.7 Hz, 1 H, 6-H), 7.06 (d, J = 9.5 Hz,
1 H, 3-H), 3.43 (m, 2 H, CH2CH2CH2CH3), 1.74 (m, 2 H,
CH2CH2CH2CH3), 1.49 (m, 2 H, CH2CH2CH2CH3), 0.98 (t, J =
[5] a) M. Makosza, Russ. Chem. Bull. 1996, 45, 491–504; b) M.
˛
Makosza, K. Stalin´ski, Chem. Eur. J. 1997, 3, 2025–2031; c)
M. Makosza, K. Stalin´ski, Pol. J. Chem. 1999, 73, 151–161.
˛
˛
7.2 Hz, 3 H, CH CH CH CH ) ppm. IR (Nujol): ν = 3289 (N–H),
˜
2
2
2
3
[6] a) A. F. Pozharskii, A. V. Gulevskaya, V. V. KuzЈmenko, Chem.
Heterocycl. Compd. 1988, 24, 1404–1405 (Engl. Transl.); b)
A. V. Gulevskaya, A. F. Pozharskii, L. V. Lomachenkova,
Chem. Heterocycl. Compd. 1990, 26, 1316–1317 (Engl. Transl.);
c) A. V. Gulevskaya, A. F. Pozharskii, S. V. Shorshnev, E. A.
Zheltushkina, Chem. Heterocycl. Compd. 1994, 30, 1083–1086
(Engl. Transl.); d) A. V. Gulevskaya, D. V. Besedin, A. F. Pozh-
arskii, Russ. Chem. Bull. Int. Ed. 1999, 48, 1150–1153; e) D. V.
Besedin, A. V. Gulevskaya, A. F. Pozharskii, Mendeleev Com-
mun. 2000, 10, 150–151; f) A. V. Gulevskaya, B. U. W. Maes,
C. Meyers, W. A. Herrebout, B. J. van der Veken, Eur. J. Org.
Chem. 2006, 5305–5314; g) A. V. Gulevskaya, B. U. W. Maes,
C. Meyers, Synlett 2007, 71–74; h) A. V. Gulevskaya, A. F.
Pozharskii, Russ. Chem. Bull. Int. Ed. 2008, 57, in press (re-
view).
3138 (C–H arom.), 1632 and 1561 (C–C arom.), 1517 (NO2,
as) cm–1. UV (CHCl3): λmax (lg ε) = 266 (3.63), 324 (3.11), 334
(3.11), 425 nm (3.83). MS (70 eV): m/z (%) = 244 (76) [M]+, 201
(76), 184 (12), 171 (15), 155 (100), 140 (13), 128 (53), 115 (44), 101
(16), 77 (17), 63 (12), 41 (29). C14H16N2O2 (244.29): calcd. C 68.83,
H 6.60, N 11.47; found C 69.05, H 6.41, N 11.29.
4-Nitro-N-propylnaphthalen-1-amine (15a): Yield 51 mg, 22%
(Method B). Orange crystals with m.p. 163–165 °C (MeOH). 1H
NMR (250 MHz, CDCl3, 30 °C): δ = 9.03 (d, J = 8.8 Hz, 1 H, 5-
H), 8.48 (d, J = 8.9 Hz, 1 H, 3-H), 7.80 (d, J = 8.4 Hz, 1 H, 8-H),
7.70 (ddd, J = 6.9, 8.8, 1.3 Hz, 1 H, 6-H), 7.52 (ddd, J = 6.9, 8.4,
1.2 Hz, 1 H, 7-H), 6.50 (d, J = 8.9 Hz, 1 H, 2-H), 5.27 (br., 1 H,
NH), 3.36 (m, 2 H, CH2CH2CH3), 1.83 (m, 2 H, CH2CH2CH3),
[7] B. Szpakiewicz, M. Grzegozek, Russ. J. Org. Chem. 2004, 40,
˙
1.09 (t, J = 7.4 Hz, 3 H, CH CH CH ) ppm. IR (Nujol): ν = 3399
˜
2
2
3
829–833.
(N–H), 1577 (C–C arom.), 1365 (NO2, s) cm–1. UV (CHCl3): λmax
[8] M. Woz´niak, M. Grzegozek, W. Roszkiewicz, B. Szpakiewicz,
˙
(lg ε) = 271 (4.20), 338 (3.69), 447 nm (3.84). MS (70 eV): m/z (%)
Recl. Trav. Chim. Pays-Bas 1995, 114, 13–17.
Eur. J. Org. Chem. 2009, 564–574
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
573

A. V. Gulevskaya, B. U. W. Maes et al.
FULL PAPER
[9] a) I. Huertas, I. Gallardo, J. Marquet, Tetrahedron Lett. 2000,
41, 279–281; b) I. Huertas, I. Gallardo, J. Marquet, Tetrahedron
Lett. 2001, 42, 3439–3441; c) I. Gallardo, G. Guirado, J. Mar-
quet, Eur. J. Org. Chem. 2002, 251–259.
[10] a) P. Gangopadhyay, S. Venugopal Rao, D. Narayano Rao,
T. P. Radhakrishnan, J. Mat. Chem. 1999, 9, 1699–1705; b) P.
Gangopadhyay, T. P. Radhakrishnan, Chem. Mater. 2000, 12,
3362–3368.
lowing expression: ω = µ2/2η (µ is electronic chemical potential
and η is the chemical hardness). Both quantities may be ap-
proached in terms of the one-electron energies of the HOMO
and LUMO frontier molecular orbitals (EHOMO and ELUMO
)
as µ ≈ (EHOMO + ELUMO)/2 and η ≈ EHOMO – ELUMO, respec-
tively. The local electrophilicity index (ωk) condensed to atom
k is obtained by projecting the global quantity onto any atomic
center k in the molecule by using the electrophilic Fukui func-
tion (i.e., the Fukui function for nucleophilic attack, fk+), re-
[11] a) R. L. Melo, L. C. Alves, E. Del Nery, L. Juliano, M. A. Ju-
liano, Anal. Biochem. 2001, 293, 71–77; b) B. Bag, P. K. Bhar-
adwaj, J. Phys. Chem. B 2005, 109, 4377–4390.
+
sulting in: ωk = fk ω. The Fukui function for nucleophilic
+
+
attack fk is defined as fk = ρN+1(k) – ρN(k), where ρN(k) is
the electron density at a point k in space around the molecule,
N corresponds to the number of electrons in the neutral mole-
cule, and N + 1 refers to the number of electrons in the corre-
sponding radical anion (obtained by adding an electron to the
LUMO of the neutral molecule); a) R. G. Parr, L. von Szent-
pály, S. Liu, J. Am. Chem. Soc. 1999, 121, 1922–1924; b) R. G.
Parr, R. G. Pearson, J. Am. Chem. Soc. 1983, 105, 7512–7516;
c) L. R. Domingo, M. J. Aurell, P. Pérez, R. Contreras, J. Phys.
Chem. A 2002, 106, 6871–6875; d) L. R. Domingo, M. J. Aur-
ell, P. Pérez, R. Contreras, Tetrahedron 2003, 59, 3117–3125; e)
P. Geerlings, F. De Proft, W. Langenaeker, Chem. Rev. 2003,
103, 1793–1874.
[12] a) F. Bell, J. Chem. Soc. 1929, 2784–2787; b) H. H. Hodgson,
R. E. Dean, J. Chem. Soc. 1950, 820–822; c) H. H. Hodgson,
D. E. Hathway, J. Chem. Soc. 1945, 543–545; d) C. F. Bernas-
coni, R. H. de Rossi, J. Org. Chem. 1976, 41, 44–49; e) P. Bel-
trame, M. Simonetta, Gazz. Chim. Ital. 1962, 92, 351–364; f) A.
Kirsch, C. Krieger, H. A. Staab, F. A. Neugebauer, Tetrahedron
Lett. 1994, 35, 8365–8368; g) H. A. Staab, A. Kirsch, T. Barth,
C. Krieger, F. A. Neugebauer, Eur. J. Org. Chem. 2000, 1617–
1622.
[13] H. Günther, NMR Spectroscopy. An Introduction, Wiley,
Chichester, 1980 (Russian Translation, Mir, Moscow, 1984,
pp. 134–135).
[14] a) A. D. Becke, J. Chem. Phys. 1993, 98, 5648–5652; b) C. Lee,
W. Yang, R. G. Parr, Phys. Rev. B 1988, 37, 785–789; c) W. J.
Hehre, L. Radom, P. v. R. Schleyer, J. A. Pople, Ab initio Mo-
lecular Orbital Theory, Wiley, New York, 1986; d) M. J. Frisch,
G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R.
Cheeseman, J. A. Montgomery Jr., T. Vreven, K. N. Kudin,
J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V. Barone,
B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G. A. Petersson,
H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J.
Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H.
Nakai, M. Klene, X. Li, J. E. Knox, H. P. Hratchian, J. B.
Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E.
Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli,
J. W. Ochterski, P. Y. Ayala, K. Morokuma, G. A. Voth, P. Sal-
vador, J. J. Dannenberg, V. G. Zakrzewski, S. Dapprich, A. D.
Daniels, M. C. Strain, O. Farkas, D. K. Malick, A. D. Rabuck,
K. Raghavachari, J. B. Foresman, J. V. Ortiz, Q. Cui, A. G. Ba-
boul, S. Clifford, J. Cioslowski, B. B. Stefanov, G. Liu, A. Lia-
shenko, P. Piskorz, I. Komaromi, R. L. Martin, D. J. Fox, T.
Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara, M.
Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M. W.
Wong, C. Gonzalez, J. A. Pople, Gaussian 03, revision C.01,
Gaussian Inc., Wallingford CT, 2004.
[16]
a) I. Gallardo, G. Guirado, J. Marquet, J. Org. Chem. 2002,
67, 2548–2555; b) C. E. S. Alvaro, N. S. Nudelman, J. Phys.
Org. Chem. 2005, 18, 880–885; c) T. Kavitha Devi, G. Achaiah,
V. Malla Reddy, J. Indian Chem. Soc. 1988, 65, 567–570; d)
S. D. Ross, Tetrahedron 1969, 25, 4427–4436; e) W. Fleisch-
hacker, M. Köhl, Tetrahedron Lett. 1982, 23, 1659–1660; f) B.
Gierczyk, B. Łeska, B. Nowak-Wydra, G. Schroeder, G.
˛
Wojciechowski, F. Bartl, B. Brzezinski, J. Mol. Struct. 2000,
524, 217–225; g) V. L. Plakidin, V. N. Vostrova, Zh. Org. Khim.
1982, 18, 342–352; h) L. Horner, M. Rocker, Phosphorus Sulfur
1987, 32, 99–103; i) N. N. Makhova, V. Yu. Petukhova, L. I.
Khmel’nitskii, Russ. Chem. Bull. 1982, 31, 1858–1862; j) N. N.
Makhova, V. Yu. Petukhova, L. I. Khmel’nitskii, Russ. Chem.
Bull. 1982, 31, 2052–2056; k) J. H. Gorvin, D. P. Whalley, J.
Chem. Soc. Perkin Trans. 1 1979, 1364–1370.
J. M. Gardiner, C. R. Loyns, C. H. Schwalbe, G. C. Barrett,
P. R. Lowe, Tetrahedron 1995, 51, 4101–4110.
a) G. Galliani, B. Rindone, Synth. Commun. 1976, 6, 403–408;
b) E. L. Teuten, R. N. Loeppky, Org. Biomol. Chem. 2005, 3,
1097–1108.
[17]
[18]
[19] H. Firouzabadi, B. Vessal, M. Naderi, Tetrahedron Lett. 1982,
23, 1847–1850.
[20] S. P. Gromov, Russ. Chem. Bull. Int. Ed. 1994, 43, 1041–1043.
Received: July 25, 2008
[15] The global electrophilicity index (ω) measures the stabilization
in energy when the system acquires an additional electronic
charge (∆N) from the environment. It is described by the fol-
Published Online: December 12, 2008
574
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 564–574