G Model
CCLET-2699; No. of Pages 3
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G. Meng et al. / Chinese Chemical Letters xxx (2013) xxx–xxx
Table 1
Nitration of aromatic compounds using TN.
Ar–H ! Ar–NO2.
Entry
Substrate
Product
Time (h)
Yield (%)a
1
2
Benzene
Nitrobenzene
4.5
1.5
0.2
5.0
5.0
5.0
5.0
5.0
1.0
1.0
14.0
1.3
100
80
Benzyl cyanide
4-Nitrobenzyl cyanide
3
Toluene
4-Nitrotoluene
37
4
4-Hydroxy benzaldehyde
2-Methyl-3-chloroacetaniline
Phenol
2-Nitro-4-hydroxybenzaldehyde
4-Nitro-2-methyl-3-chloroacetaniline
4-Nitrophenol
28
5
18
6
13
7
4-Fluorobenzaldehyde
2-p-Tolyl propanoic acid
Acetanilide
2-Nitro-4-fluoro benzaldehyde
2-(4-Methyl-3-nitrophenyl)propanoic acid
4-Nitroacetanilide
13
8
11
9
100
50
10
11
12
4-Methylacetanilide
4-Methoxyacetanilide
Chlorobenzene
N-(4-Methyl-3-nitrophenyl)acetamide
N-(4-Methoxy-3-nitrophenyl)acetamide
1-Chloro-2,4-dinitrobenzene
97
100
a
Unisolated yield.
S. HNO3
S. HNO3
NH2
. NO2
S
S
H2O
+
H+
HNO3
+
+
+
H2O
H2N
H2N
NH2
H2N
NH2
H2N
NH2
Specialactive reagent
1
Scheme 3. Nitration with TN via plausible intermediate.
Scheme 1. Preparation of thiourea nitrate (TN).
S . HNO3
(entries 10–11). In the cases of aldehyde groups, the reaction
of TN with substituted aromatic aldehyde gave relatively poor
yields (entries 4, 7). The results of nitration are summarized in
Table 1.
H2SO4
Ar
H
Ar NO2
+
H2N
NH2
Scheme 2. Nitration of aromatic compounds using TN.
When nitrating with TN, it is difficult to mono-nitrate aromatic
substrates with electron withdrawing groups. This is the opposite
of nitrating with urea nitrate [5] or guanidinium nitrate [2], in
which it is difficult to mono-nitrate aromatic substrates with
electron donating groups. In the two extreme examples with good
yield shown in entry 1 and entry 12, the substrates bears no group
or one moderately deactivating group on the aromatic ring,
respectively. Aromatic substrates with electron withdrawing
groups are very suitable for the nitration with TN (entry 12).
Electron donating groups as activating group on the benzene are
also quite suitable for the nitration with TN (entry 9).
Traditional mechanisms of nitration include high temperature
reaction and free radicals on electrophilic aromatic substitution or
single-electron transfer (SET) on aromatic hydrocarbons [13].
However, neither of these mechanisms could completely explain
the nitration result with TN. Therefore, we proposed that a
different, complex mechanism might exist in the nitration process
of TN due to the difference between the volume of the sulfur atom
in thiourea and the oxygen atom in urea. S is bulkier and more
polarizable than O, which makes the TN behave differently in the
SET process (Scheme 3).
cooled down below 0 8C with a salt-ice bath. While keeping the
temperature below 0 8C, aromatic compound (0.02 mol) was added
to the mixture, followed by slow addition of thiourea nitrate 1
(2.8 g, 0.02 mol). After the addition of 1 was complete, the mixture
was allowed to warm up to room temperature and then stirred for
an additional 0.2–5 h (Table 1) at room temperature. The reaction
mixture was slowly poured onto ice water (250 mL). The aqueous
layer was extracted with ethyl acetate (3ꢀ 50 mL). The combined
ethyl acetate layer was washed with saturated brine (25 mL) and
water (25 mL) and then dried (anhydrous Na2SO4). After evapora-
tion of the solvent, a brown residue was obtained. The content of
the crude product was determined by LC-MS. The crude product
was purified by column chromatography [12].
3. Results and discussion
The reaction of 1 in 98% sulfuric acid with benzene (entry 1)
was first explored with high yield. Encouraged by this good
result, we further investigate the nitration of TN with other
aromatic compounds bearing different substituted groups on the
benzene ring (entries 2–12). The substituted groups were chosen
according to their electronic properties, which include strongly
electron withdrawing groups (entry 2), activating groups (in
entries 3, 4, 5, 6, 8, 9, 10, 11) and deactivating groups (in entry 4,
5, 7, 12). We found that mono-nitrations were obtained in
excellent yield for unsubstituted benzene (entry 1). Di-nitration
was also obtained in excellent yields for nitrobenzene (entry 12).
The mono-nitrated products were also obtained for entries 2–11.
Moreover in all of the monosubstituted substrates (entries 2, 3,
6), only the p-substituted nitro compounds were obtained
regioselectively. Interestingly, the nitration of acetanilide (entry
9) with TN ended up without any undesired starting material.
Introducing a methyl or a methoxy group at the para position of
the acetylamino group could improve the nitration yields
Therefore, we suggest that TN is not only a source of nitrate
ions, which are converted to complexed nitric acid upon
dissolution in sulfuric acid, but it also functions as the actual
active nitrating agent with some unique behaviors (Scheme 3).
4. Conclusion
In conclusion,
a series of aromatic compounds bearing
moderately activating, activating, weakly deactivating and strong-
ly deactivating groups have been nitrated with TN in different
yields to give the corresponding nitro compounds. TN offers
advantages in ease of preparation, low cost, and simple handling in
the nitration of aromatic substrates, making it
a plausible
alternative for nitrating aromatic compounds, especially when
traditional nitration reagents are less successful.
Please cite this article in press as: G. Meng, et al., The novel usage of thiourea nitrate in aryl nitration, Chin. Chem. Lett. (2013), http://