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J. Almog et al. / Tetrahedron Letters 47 (2006) 8651–8652
Table 1. Nitration of deactivated benzenes with UN and with NU
Run
Substrate
Product of UN nitration
Total yield (%)
(isolated)
Product of NU nitration
Total yield
(%) (isolated)
1
2
Nitrobenzene
Benzonitrile
1,3-Dinitrobenzene (91%),
1,2-dinitrobenzene (9%)
3-Nitrobenzamide (78%),a
3-nitrobenzonitrile (10%),
2-nitrobenzonitrile (12%)
3-Nitrobenzoic acid
3-Methyl-6-nitrobenzoic acid (58%),
3-methyl-2-nitrobenzoic acid (22%),
3-methyl-4-nitrobenzoic acid (12%)
2-Methoxy-5-nitrobenzoic acidb
2,4-Dinitrotoluene
93
1,3-Dinitrobenzene (93%),
1,2-dinitrobenzene (7%)
3-Nitrobenzonitrile (86%),
2-nitrobenzonitrile (14%)
68
85
90
3
4
Benzoic acid
m-Toluic acid
97
94
3-Nitrobenzoic acid
71
75
3-Methyl-6-nitrobenzoic acid (74%),
3-methyl-2-nitrobenzoic acid (23%),
3-methyl-4-nitrobenzoic acid (3%)
2-Methoxy-5-nitrobenzoic acidb
2,4-Dinitrotoluene
5
6
7
o-Anisic acid
p-Nitrotoluene
o-Nitrotoluene
93
99
98
100
99
98
2,4-Dinitrotoluene (70%),
2,6-dinitrotoluene (30%)
2,4-Dinitrotoluene (70%),
2,6-dinitrotoluene (30%)
a Formed by hydrolysis of the initially obtained, 3-nitrobenzonitrile.
b Structure determined by 1H NMR.
Both UN and NU were applied to the nitration of sev-
eral deactivated and moderately deactivated benzene
derivatives. In a typical nitration procedure, solid UN
(20 mmol) was added in small portions over a period
of 30 min to a stirred solution of an aromatic substrate
(10 mmol) in concentrated sulfuric acid (10 ml) main-
tained at 0 °C. The temperature was then raised to
25 °C and stirring was continued for an additional
24 h. The final solution was poured onto crushed ice
(100 g) and extracted twice with 50 ml of chloroform.
The combined extract was washed once with 50 ml of
10% sodium carbonate solution and once with 50 ml
deionized water. After drying over magnesium sulfate,
the solvent was evaporated to produce a thick oil which
spontaneously crystallized after several hours. The crys-
tals were dried under vacuum. The product structure
was confirmed based on GC and MS analysis (compar-
ison with an authentic sample).
The latter was not detected at all in our product mixture.
Strongly deactivated substrates such as 1,4-dinitrobenz-
ene, o-phthalic acid and pyridine did not undergo nitra-
tion using either UN or NU even when the mixture was
heated above 60 °C.
We conclude that NU and UN are a unique category of
novel nitration agents that are remarkably active and
regioselective in the aromatic nitration of moderately
deactivated substrates. The nature and isomer distribu-
tion of the nitrated products clearly implies a mecha-
nism involving electrophilic aromatic substitution.
Caution: UN and NU are both potential explosives and
must be handled with care, similarly to ammonium
nitrate.15
References and notes
An identical procedure was used with NU in place of
UN.
1. Gasser, J. K. R.; Penny, A. J. Agric. Sci. 1967, 69, 139.
2. Vogel, A. I. A Textbook of Practical Organic Chemistry;
Longmans: London, 1971, p 442.
Table 1 summarizes the nitration experiments of deacti-
vated aromatic compounds using UN and NU. It was
noticed that only one nitro group was introduced,
regardless of the molar ratio between reagent and sub-
strate (up to a ratio of 4:1). The enhanced regioselectiv-
ity of nitration with UN over the classical mixed-acid
procedure was best demonstrated by the products ob-
tained with benzoic acid as a substrate. While the latter
process produced a mixture of 3-nitrobenzoic acid
(79%), 2-nitrobenzoic acid (20%) and 4-nitrobenzoic
acid (1%),13 nitration with UN produced only 3-nitro-
benzoic acid in a nearly quantitative yield (Table 1).
Similarly, the nitration of 4-nitrotoluene produced, with
99% selectivity, the preferred isomer 2,4-dinitrotoluene
while classical batch nitration with mixed-acids yields
80:20 molar ratio of 2,4-dinitrotolune and 2,6-dinitro-
toluene.14 UN and NU nitrations of nitrobenzene were
also (though marginally) more chemo- and regio-selec-
tive in comparison with the traditional method, which
is known to form 10% of 1,2-dinitrobenzene along with
2% of 1,4-dinitrobenzene and 2% of 4-nitrophenol.14
3. Almog, J.; Klein, A.; Tamiri, T.; Shloosh, Y.; Abramo-
vich-Bar, S. J. Forensic Sci. 2005, 50, 582.
4. Worsham, J. E.; Busing, W. R. Acta Cryst. B 1969, 25,
572.
5. Harkema, S.; Feil, D. Acta Cryst. B 1969, 25, 589.
6. Majumdar, M. P.; Kudav, N. A. Indian J. Chem. 1976,
14B, 1012.
7. Nabar, V. B.; Kudav, N. A. Indian J. Chem. 1977, 15B, 89.
8. Sura, I. P.; Ramana, M. M. V.; Kudav, N. A. Synth.
Commun. 1988, 18, 2161.
9. Mundla, S. R. Tetrahedron Lett. 2000, 41, 4277.
10. Nagarajan, R.; Muralidharan, D.; Perumal, P. T. Synth.
Commun. 2004, 34, 1259.
11. Davis, T. L.; Blanchard, K. C. J. Am. Chem. Soc. 1929, 51,
1794.
12. Shead, A. C. Mikrochim. Acta 1967, 5, 936.
13. Beer, C. T.; Dickens, F.; Salmony, D. Biochem. J. 1951,
49, 700.
14. Ullmann’s Encyclopedia of Industrial Chemistry. J. Wiley
& Sons 2005 (web version).
15. The Health and Safety at Work Act 1974, Chapter 37,
HMSO ISBN 0 10 543774 3.