Mendeleev
Communications
Mendeleev Commun., 2013, 23, 174–175
Interaction of hexamethylphosphoric triamide with m-dinitrobenzenes
Mikhail D. Dutov* and Olga V. Serushkina
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russian Federation.
Fax: +7 499 135 5328; e-mail: dutov@ioc.ac.ru
DOI: 10.1016/j.mencom.2013.05.019
Heating of 1-X-3,5-dinitrobenzenes (X is an electron-withdrawing group) in hexamethylphosphoric triamide affords the corresponding
1-X-3-dimethylamino-5-nitrobenzenes.
Me
Continuing our studies on the replacement of a nitro group in
1,3,5-trinitrobenzene (TNB) by secondary amines,1 we found
that attempted reaction between TNB and diphenylamine in
hexamethylphosphoric triamide (HMPA) afforded N,N-dimethyl-
3,5-dinitroaniline rather than expected 3,5-dinitrotriphenylamine.
The use of HMPA as a source of the dimethylamino group was
reported previously.2 Thus, a halogen was displaced by dimethyl-
amino group during heating of o- and p-halonitrobenzenes in
HMPA. In case of o- and p-dinitrobenzenes, the nitro group was
substituted. In p-nitrophenol and p-nitroanisole, an electron-donor
oxygen function was replaced by the dimethylamino group. Benzo-
nitriles bearing o- or p-halogen form the corresponding amino
nitriles. Note that in case of m-chloronitrobenzene and m-chloro-
benzonitrile the substitution practically did not occur.
In a more detailed study of the interaction between TNB 1a
and HMPA, it was found that the reaction began at 150°C and
was complete within 10 h. The preparative yield of N,N-dimethyl-
3,5-dinitroaniline 2a was 43%, and much resin was formed.
TNB analogues 1b–e containing other electron-acceptor groups
behaved analogously (Scheme 1).
Me
O2N
O2N
N
HMPA
P(NMe2)2
O
X
X
O2N
O2N
NMe2
NMe2
– XP(O)(NMe2)2
X
P(NMe2)2
O
Scheme 2
implies XP(O)(NMe2)2 to be a leaving group, which seems
unlikely in the cases of halogen and nitro group. Another mecha-
nism proposed by Gupton et al.2 (Scheme 3), which involves
thermal dissociation of HMPA, appears to be more preferable.
O
P
O
P
Me
Me
Me
Me
Me
Me
Me
Me
N
N
N
N
N
N
Me
Me
Me
Me
X
X
Scheme 3
(Me2N)3PO
150 °C
In this case, the resulting Me2N– further acts as an ordinary
nucleophile. We anticipated that based on this hypothesis one
can introduce any secondary amine into TNB in a higher yield
than that achieved earlier. Unfortunately, attempted interaction
between phosphoric acid tripyrrolidide and TNB gave none of
the product. Therefore, the mechanism of the interaction of HMPA
with aromatic substrates should be further studied.
O2N
NO2
O2N
NMe2
1a–e
2a–e
a X = NO2, 43%
b X = CF3, 41%
d X = PhSO2, 50%
e X = CN, 8%
c X = SO2Me, 40%
Scheme 1
The structures of the synthesized compounds were determined
based on 1H NMR spectroscopy, mass spectrometry (in all cases
molecular ions were detected) and elemental analysis.†
It could be expected that p-dinitrobenzene would have been
much more reactive than TNB. However, that reaction required
longer time of 14.5 h, and the yield of N,N-dimethyl-4-nitro-
aniline 3 was 56%.
†
Starting compounds 1c and 1d were prepared as described.4,5
General experimental procedure (Caution! HMPA is not a friendly
solvent). A solution of 0.5 g of a starting substrate in 15 ml of HMPA was
kept at 155–160°C until the reactant was consumed (TLC; eluent, CHCl3).
The reaction mass was cooled and poured into 150 ml of ice water. The
precipitate was filtered off, washed with water and dried. The crude product
was dissolved in chloroform, and the solution was filtered through a silica
gel bed. The filtrate was evaporated, and the residue was crystallized from
methanol.
1H NMR spectra were measured on a Bruker AM-300 spectrometer.
2a: reaction time 10.5 h, yield 43%, mp 161–162°C (lit.,6 mp 164°C).
1H NMR (DMSO-d6) d: 3.10 (s, 6H), 7.71 (s, 2H), 7.99 (s, 1H).
2b: reaction time 20 h, yield 41%, mp 68–69°C. 1H NMR (DMSO-d6)
d: 3.07 (s, 6H), 7.27 (s, 1H), 7.59 (s, 2H).
2c: reaction time 7.5 h, yield 40%, mp 149–150°C. 1H NMR (CDCl3)
d: 3.11 (s, 3H), 3.14 (s, 6H), 7.43 (s, 1H), 7.67 (s, 1H), 7.98 (s, 1H).
Unlike p-dinitrobenzene, m-dinitrobenzene was stable under
these conditions and remained unchanged within 9.5 h. In the
case of 3,5-dinitrobenzonitrile 1e, the substitution product 2e
wasobtainedinayieldofonly8%.However,unlikep-nitroanisole,
3,5-dinitroanisole did not form N,N-dimethyl-3,5-dinitroaniline.
We identified 3,5-dinitrophenol as the only product of this reaction
in addition to a significant quantity of resins. 3,5-Dinitrophenyl
phenylsulfide was isolated unchanged after 11.5 h at 150°C,
although the 1H NMR spectrum of the crude product contained
weak signals, which can be attributed to expected 3-dimethyl-
amino-5-nitrophenyl phenylsulfide.
Pedersen et al.3 proposed the reaction mechanism for these
transformations, which is outlined in Scheme 2. This mechanism
© 2013 Mendeleev Communications. All rights reserved.
– 174 –
Dutov, Mikhail D.
