Highly efficient nitration of phenolic compounds using some nitrates and oxalic acid under solvent-free conditions

Article abstract of DOI:10.3184/030823411X12935549795603

Nitrophenols can be obtained by direct nitration of phenols with some nitrates and oxalic acid at room temperature in moderate to high yields under solvent-free conditions. A small amount of water proved to be important in the initial period of the reaction.

Full text of DOI:10.3184/030823411X12935549795603

JOURNAL OF CHEMICAL RESEARCH 2011
RESEARCH PAPER 101
FEBRUARY, 101–103
Highly efficient nitration of phenolic compounds using some nitrates and
oxalic acid under solvent-free conditions
Li Ji, Chao Qian*, Mei-xin Liu and Xin-zhi Chen
Department of Chemical and Biochemical Engineering, Zhejiang University. NO.38, Zheda Road, Hangzhou 310027, P. R. China
Nitrophenols can be obtained by direct nitration of phenols with some nitrates and oxalic acid at room temperature
in moderate to high yields under solvent-free conditions. A small amount of water proved to be important in the
initial period of the reaction.
Keywords: nitration, solvent-free, phenols, oxalic acid, nitrate
Aromatic nitration is an immensely important industrial pro-
cess and nitro aromatic compounds so produced are widely
used as explosives and act as key substrates for the synthesis
of useful materials such as dyes, pharmaceuticals, perfumes
and plastics.1–3 The nitration of highly reactive aromatic
compounds, such as phenols and anilines, involves unsolved
problems pertaining to regioselectivity, overnitration and
competitive oxidation of substrates.4 Because nitrophenols
are quite important organic synthetic intermediates, it is still
an interesting and meaningful subject of organic synthesis to
develop the nitrating procedures of phenolic compounds under
mild conditions.
Recently, the nitration of phenolic compounds using nitrates
such as AgNO3,8 Bi(NO3)3,9–11 Fe(NO3)3·9H2O,12 Cu(NO3)2,13
(Me4N)NO3,14 Mg(NO3)2·6H2O,15 Ca(NO3)2,16 NaNO2,17–19
NaNO3,20 (NH4)2Ce(NO3)6,21 ZrO(NO3)2.xH2O,22 VO(NO3)3,23
Fe(NO3)3·1.5N2O4,24 Cu(NO3)2·N2O4,24 has been reported and
gave satisfactory results. However, many procedures above-
mentioned required the assistance of special co-reagents or
extraordinary solvents, and the rest required unusual nitrates.
In some cases, the nitration has been performed in expensive
media such as ionic liquids and microemulsions.25 We now
report a novel nitration method using a combination of nitrates
and solid acid, which reduces the consumption of acid and
simplifies the procedures.
phenols, owing to its appropriate pKa value and its prevention
of the oxidative side reactions. Oxalic acid can be produced
both by chemical and fermentative processes, the former being
more common nowadays. Oxalic acid is an efficient and
cost-effective reagent for solvent-free nitration.
In view of safety, toxic transition-metal nitrates such as
Cr(NO3)3·9H2O, Hg(NO3)2, Cu(NO3)2·6H2O were avoided.
By comparing the result of the mononitration of 2, 6-di-tert-
butylphenol using different nitrates as shown in the Table 1, it
is obvious that common alkali metal nitrates, alkali earth metal
nitrates and aluminium nitrate have similar effects.
Having gained an understanding of the factors that influence
the nitration process, we explored the scope and limitation
of this method. Further nitration results are summarised in
Table 2.
During the experiments it was found unexpectedly that if
nitrates were vacuum-desiccated to ensure no free water, the
moisture-free phenols did not react with nitrates in the pres-
ence of oxalic acid. However, the same phenols were nitrated
smoothly by using wet nitrates under the same conditions.
Furthermore, the reactions could be performed successfully
after adding several drops of water to the dry reaction
mixtures. The process is demonstrated in Fig. 2.
Because of this phenomenon, it is concluded that water,
more specifically free water, plays an important role in the
initial period of the reaction. The addition of small amounts of
water accelerates the disaggregation of the reactant crystals
Results and discussion
The selection of best solid acid is the first task for the present
study. Different solid acids such as monochloroacetic acid
(pKa = 2.86, m.p. 61–63 °C), trichloroacetic acid (pKa = 0.64,
m.p. 58 °C), p-TsOH (pKa = –6.62, m.p. 57.5 °C), malonic
acid (pKa1 = 2.85, m.p. 136 °C), citric acid (pKa1 = 3.13, m.p.
153 °C), maleic acid (pKa1 = 1.83, m.p. 139–140 °C) were used
in the nitration of phenolic compounds. The procedure used to
grind the acid, the nitrate and the substrate independently in
a pestle and mortar. Any products were then worked up. How-
ever, the above acids either do not work in the solvent-free
conditions or gave a poor yield of the expected products
even when a few drops of water were added to the reaction
mixture.
Table 1 The nitration of 2,6-di-tert-butylphenol with oxalic
acid and nitratesa
Entry Nitrate
Amount (COOH)2·2H2O Time Yieldb
of nitrate
/mmol
/mmol
/min
/%
1
2
3
4
5
6
7
8
NaNO3
20
20
30
30
30
15
15
10
20
30
20
30
30
30
30
30
40
40
40
30
30
30
30
30
41
65
68
87
85
90
90
92
NaNO3
NaNO3
NaNO3
KNO3
Mg(NO3)2·6H2O
Ca(NO3)2·4H2O
Al(NO3)3·9H2O
Finally we found that oxalic acid (pKa1 = 1.27, m.p. 189 °C,
usually existing in the form of dihydrate, m.p. 103 °C) might
be the most suitable solid acid in the solvent-free nitration of
a Reaction conditions: 2,6-di-tert-butylphenol (20 mmol), grind-
ing at room temperature.
b Isolated yield.
Fig. 1 Nitration of phenols with oxalic acid and nitrates.
* Correspondent. E-mail: supmoney@163.com

102 JOURNAL OF CHEMICAL RESEARCH 2011
Table 2 Mononitration of phenolic compounds to the corresponding nitro derivatives with oxalic acid, nano3 under solvent-free
condition at room temperaturea
Entry
Substrate
Product
Time/min
Yieldb/%
M.p./°C
Found
44–45
Reported
45–4727
1
21
65
90
86
87
93
89
10
116–117
31–32
117–11927
2
3
4
5
6
15
15
30
10
15
3128
70–72
70–7327
154–15629
9128
153–154
88–89
102–104
10530
a Reaction conditions: substrate (20 mmol),oxalic acid (30 mmol) and NaNO3 (30 mmol), grinding at room temperature (see safety
caution in Experimental).
b Isolated yield.
Fig. 2 (a) Oxalic acid dihydrate, sodium nitrate and 2,6-di-tert-butylphenol ground independently and mixed at room temperature
(see safety caution in Experimental). NO REACTION! (b) Drops of water are added and with further grinding. (c) and (d) The colour
of mixture changes.(e) Liquid phase appears. (f) Wet crystalline solid.
and the formation of a liquid phase,5 which can be beneficial
to solvent-free reactions. Very reactive aromatic compounds
are susceptible to a ‘nitrous acid’-catalysed process and this
reaction may involve intermediate nitroso compounds.3 The
possible mechanism is shown in Fig. 3.
Experimental
All the phenols and nitrates were vacuum desiccated at low tempera-
ture. Yields refer to isolated pure products. The nitration products
were characterised by comparison of their 1H NMR, TLC and physical
data with authentic samples.

JOURNAL OF CHEMICAL RESEARCH 2011 103
1
154–156 °C]. H NMR (DMSO-d6, 400 MHz, TMS) δ 1.39 (18H, s,
6×CH3), 7.98 (2H, s, Ar), 8.47 (1H, s, ArOH).
Conclusion
In summary, cheapness and availability of nitration reagents,
easy and clean work-up and good yield make this method
attractive for organic chemists.
We thank the National Natural Science Foundation of China
(20776127, 21006087), and the Natural Science Foundation of
the Zhejiang Province (Y4100147) for financial support.
Received 11 September 2010; accepted 29 November 2010
Paper 1000347 doi: 10.3184/030823411X12935549795603
Published online: 10 February 2011
Fig. 3 Proposed mechanism of nitration with nitrates and
oxalic acid.
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